Rat model of chronic tympanic membrane perforation: A longitudinal histological evaluation of underlying mechanisms

Publication date: Available online 25 December 2016
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Allen Y. Wang, Lawrence J. Liew, Yi Shen, Jeffrey T. Wang, Magnus von Unge, Marcus D. Atlas, Rodney J. Dilley
ObjectiveTo evaluate histologically the progressive development and underlying mechanisms of chronic tympanic membrane perforation (TMP) in a rat model using a two-weeks ventilation tube (VT) treatment combined with topical application of mitomycin C/dexamethasone (VT-M/D), compared with normal tympanic membrane and acute TMPs.MethodsFifty male Sprague-Dawley rats were divided into three experimental groups: a normal control group (n = 5), an acute TMP group (n = 5) (i.e. 3 days post-myringotomy) and a VT-M/D group (n = 40). The TMs were regularly assessed by otoscopy. The normal control animals were sacrificed on day 0 and the acute TMP group was sacrificed 3 days post-myringotomy for histological and immunohistochemical evaluations. The VT-M/D group was sacrificed at various time points - 14 and 17 days, 3, 4, 6, 8 and 10 weeks.ResultsOn longitudinal histological examination, compared with normal TM and acute TMP, the perforation edges at the later time points illustrated thickened stratified squamous epithelium rimming around the edges, significant increase in keratin and collagen deposition, increased macrophage infiltration as well as reduced cellular proliferation. Three phases of TMP healing process were identified - the acute healing phase (3–17 days), the transition phase (3–4 weeks) and the chronic phase (6–10 weeks).ConclusionBased on the histological results of this study, the progressive development of chronic TMPs appeared to be associated with increased epidermal thickening, collagen and keratin deposition, macrophage infiltration and reduced cellular proliferation. After the 3–4 weeks of transition phase, the TMPs seemed to have transformed into a non-healing chronic TMP between 6 and 10 weeks.



http://ift.tt/2i6JpvC

Upper Lip Reconstruction after Oncologic Resection by a Sliding Advancement Cheek Flap with Buccal Mucosal Eversion

No abstract available

http://ift.tt/2gqUshr

A Novel Technique That Protects the Lips during Orthognathic Surgery

Summary: Serious lip injuries can occur during orthognathic surgery. Although an Angle Wider device, which is commonly used during orthognathic surgery, provides some lip protection, it leaves more than half of the lip exposed to surgical instruments. Here, we describe a novel technique to protect the entire upper and lower lips during orthognathic surgery using a minilaparotomy wound edge protector (Lap-Protector). We used this method in 60 patients who have undergone orthognathic surgeries such as sagittal split ramus osteotomy and Le Fort I osteotomy since 2009, and no lip injuries have occurred. Although this technique can be somewhat challenging at first and creates some difficulty in exposing the surgical field on the lateral side, we believe that using a wound edge protector minimizes the risk of lip injury during orthognathic surgery.

http://ift.tt/2gqQllq

Topical Negative Pressure on Burns: An Innovative Method for Wound Exudate Collection

Summary: Burn wound exudate is an important source of information on the wound-healing process and systemic improvement of burn patients. Identification of biomarkers for the prediagnosis of local or systemic complications in patients will have a great impact on adapting personalized procedures in burn treatment. No efficient exudate collection method exists that offers a direct and continuous collection over time. We developed an innovative system based on the negative pressure wound therapy technique to directly collect exudate from burn wounds over several days after burn. This method did not cause any complication or pain for patients, and positive influence on wound healing was seen. Exudate samples were further used in different projects for studying biochemical profile, trace element content, kinetics of bacterial growth, and cell cytotoxicity.

http://ift.tt/2h9WEbI

Breast Desmoid Tumor after Ductal Carcinoma Treatment: Salvaging a DIEP Flap Reconstruction

No abstract available

http://ift.tt/2ho8mDb

Role of several cytokines and adhesion molecules in the diagnosis and prediction of survival of hepatocellular carcinoma

Publication date: December 2016
Source:Arab Journal of Gastroenterology, Volume 17, Issue 4
Author(s): Raim Iliaz, Umit Akyuz, Didem Tekin, Murat Serilmez, Sami Evirgen, Bilger Cavus, Hilal Soydinc, Derya Duranyildiz, Cetin Karaca, Kadir Demir, Fatih Besisik, Sabahattin Kaymakoglu, Filiz Akyuz
Background and study aimsThere is still need for accurate markers for early diagnosis of hepatocellular carcinoma (HCC) and assessment of prognosis. The aim of this study is to investigate interleukin (IL)-32, IL-1 beta, IL-18, vascular cell adhesion molecule (VCAM)-1, and epithelial cell adhesion molecule (EpCAM) in the diagnosis and assessment of prognosis of HCC.Patients and methodsFifty patients with HCC and 15 healthy volunteers were enroled into this prospective study. Serum samples were obtained at the first admission before any treatment was given. Serum IL-32, IL-1 beta, IL-18, VCAM-1, and EpCAM levels were determined using ELISA kits.ResultsThe mean age of the patient group and controls was 60±9years and 56±8years, respectively. The mean serum level of IL-32 was higher in patients with HCC than in the control subjects (65.1 vs. 14.1pg/mL; p<0.001). IL-18 levels were significantly higher in the HCC group (546.5 vs. 157.8pg/mL; p<0.001). EpCAM (20.3 vs. 1.5pg/mL; p<0.001) and VCAM (6.5 vs. 1.8μg/mL; p<0.001) levels were also higher in patients with HCC. The mean level of IL-1 beta in the HCC group was similar to that in the control subjects (1.9 vs. 1.9pg/mL; p=0.97). Fifty-eight per cent of the patients with HCC died at 7.3months (median). Cytokine levels except EpCAM did not correlate with survival (p>0.05). Alpha-foetoprotein, IL-32, IL-18, EpCAM, and VCAM had valuable cutoff levels to differentiate between patients with HCC and control group (p<0.001).ConclusionsAlthough cytokines can be a diagnostic marker for HCC, they did not have any significant prognostic value in patients with HCC. Only EpCAM may be used to determine the prognosis of HCC, thereby assisting with treatment management.



http://ift.tt/2isIfXT

Editorial Board

Publication date: December 2016
Source:Arab Journal of Gastroenterology, Volume 17, Issue 4





http://ift.tt/2hVpWgR

This second edition of “Fractures of the facial skeleton” is a soft cover book of 166 pages written for...

This second edition of "Fractures of the facial skeleton" is a soft cover book of 166 pages written for postgraduate students, trainees and practitioners dealing with facial trauma in the craniomaxillofacial region. It follows the first edition published in 2001. In 10 chapters dealing with well chosen facial trauma topics an excellent overview of the basics is provided including incidence, aetiology, general principles of treatment, emergency management of facial trauma, clinical features, imaging, treatment of hard and soft tissue injuries, post-operative care and complications.

http://ift.tt/2hVHM3s

Can a commercially available EPID dosimetry system detect small daily patient setup errors for cranial IMRT/SRS?

Publication date: Available online 24 December 2016
Source:Practical Radiation Oncology
Author(s): Emmelyn S. Hsieh, Katherine S. Hansen, Michael S. Kent, Sanjeev Saini, Sonja Dieterich
PurposeThe purpose of this study was to determine if the Sun Nuclear PerFRACTION EPID dosimetry software would be able to detect setup errors in a clinical setting and would be able to correctly identify in which direction the setup error was introduced.Methods and MaterialsA 7-field IMRT treatment plan for a centrally located tumor was developed for one phantom and five canine cadaver heads. Systematic setup errors were introduced by manually moving the treatment couch by 1mm, 3mm, and 5mm in each translational direction to assess SRS, IMRT and 3D treatment tolerances after the initial alignment was performed. An angular setup error of 5 degrees yaw was also assessed. The delivered treatment fluence was automatically imported in the Perfraction software and compared to the baseline fluence.ResultsIn the canine phantom, a 5mm shift was undetected by gamma analysis, and up to a 2cm shift had to be introduced for the gamma pass rate of 3%/3mm to fall below a 95% pass rate criteria. The same 5mm shift using 3% percent difference caused the pass rates for two fields to drop below the 95% tolerance. For each respective translational shift, the affected beam angles were consistent across the cadaver heads and correlated with the direction of translational shift. The best field pass rate, worst field pass rate, and average pass rate across all seven fields was analyzed to develop clinical guidance on parameter settings for SRS, IMRT and 3D tolerances.ConclusionsPerFRACTION 2D mode successfully detected setup errors outside the systematic error tolerance for SRS, IMRT and 3D when an appropriate analysis metric and pass/fail criteria was implemented. Our data confirms that percent difference may be more sensitive in detecting plan failure than gamma analysis.



http://ift.tt/2hdHJvz

Use of pentoxifylline and tocopherol in radiation-induced fibrosis and fibroatrophy

Radiation-induced fibrosis in the head and neck is a well-established pathophysiological process after radiotherapy. Recently pentoxifylline and tocopherol have been proposed as treatments to combat the late complications of radiation-induced fibrosis and a way of dealing with osteoradionecrosis. They both have a long history in the management of radiation-induced fibrosis at other anatomical sites. In this paper we review their use in sites other than the head and neck to illustrate the potential benefit that they offer to our patients.

http://ift.tt/2hk0UHm

Star excursion balance test for assessment of dynamic instability of the ankle in patients after harvest of a fibular free flap: a two-centre study

We aimed to show that the star excursion balance test can identify instability in the ankle of patients who have had harvest of a fibular free flap. We compared the reach distance of the operated leg against that of the non-operated leg in 26 patients who had had harvest of the flap over a period of three years from August 2009 at two different centres. The goal of the test is to reach as far as possible with one leg in eight directions while balancing on the other. We also assessed the overall function of the operated leg using the Foot and Ankle Disability Index (FADI) and the American Orthopaedic Foot and Ankle Score (AOFAS).

http://ift.tt/2i4ie1U

Postoperative radiotherapy for patients with oral squamous cell carcinoma with intermediate risk of recurrence: a case match study

Introduction/Aims: The purpose of this study was to determine the effect of postoperative radiotherapy (PORT) on recurrence and survival in patients with oral squamous cell carcinoma (OSCC) of intermediate risk of recurrence.

http://ift.tt/2hjWDnv

Anti-atherosclerosis and cardio-protective effects of the Angong Niuhuang Pill on a high fat and vitamin D3 induced rodent model of atherosclerosis

Publication date: 4 January 2017
Source:Journal of Ethnopharmacology, Volume 195
Author(s): Wen-Juan Fu, Ting Lei, Zhen Yin, Jian-Hao Pan, Yu-Shuang Chai, Xiao-Yun Xu, Yi-Xi Yan, Zhi-Hua Wang, Jian Ke, Gang Wu, Ren-He Xu, Manish Paranjpe, Lintao Qu, Hong Nie
Ethnopharmacological relevanceThe Angong Niuhuang Pill (ANP) is a well known Chinese traditional therapeutic for the treatment for diseases affecting the Central Nervous System (CNS). Components of the ANP formulation, including Bovis Calculus Sativus, Pulvis Bubali Comus Concentratus, Moschus, Margarita, Cinnabaris, Realgar, Coptidis Rhizoma, Scutellariae Radix, Gardeniae Fructus, Curcumae Radix, and Bomeolum Syntheticum, have been used for the treatment of stroke, encephalitis and emergency meningitis across Asia, especially in China for hundreds of years.ObjectiveThe goal of this study was to investigate the anti-atherosclerosis and cardio-protective effects of ANP administration using a rodent model of atherosclerosis induced by a high fat and vitamin D3.MethodsSpecific Pathogen-Free (SPF) 78 male SD rats were randomly divided into a control group and 5 atherosclerotic model groups. The atherosclerotic groups were divided to receive either Simvastatin (SVTT, 0.005g/kg), Low-dose ANP (0.125g/kg), Medium-dose ANP (0.25g/kg), and High-dose ANP (0.5g/kg). Following adaptive feeding for one week, atherosclerosis was induced and the atherosclerosis model was established. Experimental drugs (either simvastatin or ANP) or normal saline were administered intragastrically once daily for 9 weeks starting from the 8th week. A carotid artery ultrasound was performed at the 17th week to determine whether atherosclerosis had been induced. After the atherosclerosis model was successfully established, platelet aggregation rates, serum biochemical indices, apoptosis-related Bcl-2, Bax proteins levels in the heart were assayed. Pathological and histological analysis was completed using artery tissue from different experimental different groups to assess the effects of ANP.ResultsANP significantly decreased aortic membrane thickness, the maximum platelet aggregation rates, and the ratio of low density lipoprotein cholesterol (LDL) to high density lipoprotein cholesterol (HDL). In addition, ANP significantly reduced serum contents of total cholesterol, low density lipoprotein, malondialdehyde, troponin I, high-sensitivity C-reactive protein, and lactate dehydrogenase. ANP markedly improved abnormal pathological conditions of the aorta and heart, and helped to prevent myocardial apoptosis.ConclusionsWe have demonstrated that ANP has robust ant-atherosclerosis and cardio-protective effects on a high-fat and vitamin D3 – induced rodent model of atherosclerosis due to its antiplatelet aggregation, lipid regulatory, antioxidant, anti-inflammatory and anti-apoptotic properties.

Graphical abstract

http://ift.tt/2i4fVvO

Polar extracts from the berry-like fruits of Hypericum androsaemum L. as a promising ingredient in skin care formulations

Publication date: 4 January 2017
Source:Journal of Ethnopharmacology, Volume 195
Author(s): Fabiana Antognoni, Mariacaterina Lianza, Ferruccio Poli, Michela Buccioni, Claudia Santinelli, Giovanni Caprioli, Romilde Iannarelli, Giulio Lupidi, Elisabetta Damiani, Daniela Beghelli, Alessia Alunno, Filippo Maggi
Ethnopharmacological relevanceThe top flowering aerial parts of the Hypericum species are traditionally used to prepare ointments to heal cuts and burns. Sometimes even the fruits are used for these purposes. Hypericum androsaemum L., commonly known as tutsan or shrubby St. John's Wort, is a Mediterranean medicinal plant which has been traditionally used to prepare an ointment for treating cuts and wounds.Aim of the studyTo evaluate the extracts obtained from H. androsaemum red berries as functional ingredients for skin care formulations.Materials and methodsThe methanolic extract was obtained by Soxhlet extraction while the aqueous extract was prepared by decoction; their composition was determined by HPLC analysis. Their biological activities were measured in terms of proliferation and migration of human fibroblasts, inhibition of collagenase activity, and immunomodulatory effects on human peripheral blood mononuclear cells (PBMCs). In addition, we evaluated their photostability by UV spectroscopy and their protective effects against APPH-induced hemolysis in red blood cells (RBC).ResultsThe polar extracts contained significant amounts of shikimic (108,143.7–115,901.3mg/kg) and chlorogenic acids (45,781.1–57,002.7mg/kg). The main components of these extracts made an important contribution to a significant increase in human fibroblast migration. Both extracts were also active as collagenase inhibitors, with the aqueous one showing a greater inhibitory capacity (IC50 value of 88.1µg/mL), similar to that of chlorogenic acid. The kinetic parameters determined for the enzymatic reaction revealed for both aqueous extract and chlorogenic acid an uncompetitive mechanism of inhibition. The methanolic extract showed important effects on PBMCs by modulating IL-6. Both extracts proved to be photostable in the UVA/B range and protected RBC against peroxidation at low concentrations.ConclusionsH. androsaemum red berries were proven to contain phytochemicals that improve skin regeneration, hence potentially employable in skin care formulations.

Graphical abstract

http://ift.tt/2i47Jf3

Steroidogenic effect of Erxian decoction for relieving menopause via the p-Akt/PKB pathway in vitro and in vivo

Publication date: 4 January 2017
Source:Journal of Ethnopharmacology, Volume 195
Author(s): Shi Wei Wang, Ho Pan Cheung, Yao Tong, Jia Lu, Tzi Bun Ng, Yan Bo Zhang, Zhang-Jin Zhang, Kai Fai Lee, Jenny Ka Wing Lam, Stephen Cho Wing Sze
Ethnopharmacological relevanceErxian decoction (EXD), an empirical Chinese medicine formula, is effectively used in the clinical treatment of menopause-related symptoms in China. Previous data from our group show that EXD has steroidogenic effect on natural menopausal Sprague–Dawley-rats (SD-rats) as an animal model of menopause. However, the mechanistic studies on steroidogenic effects of EXD are still inadequate. Hence, the mechanisms of steroidogenic effects of EXD were studied in vitro and in vivo in this study.Materials and methodsMenopause causes a decline of endocrine function and a series of symptoms. In this study, 16–20-month-old female SD rats with a low serum estradiol level were employed. Their endocrine functions after treatment with EXD (4.1g/kg) were assessed by determination of their serum estradiol level. Proteins involved in the steroidogenic pathway including StAR, 17βHSD, 3βHSD, aromatase, and activation of phosphorylated Protein Kinase B (p-Akt/PKB), as well as estradiol receptor proteins (ERα & ERβ) after EXD treatment were analyzed. Kinase inhibition assay was conducted to confirm the mechanism of steroidogenic effects of EXD in vitro. MCF-7 and BT-483 cells were used to investigate whether EXD stimulated breast cancer cell proliferation.ResultsResults revealed a significantly ameliorated serum estradiol level, and a significantly increased expression of ovarian aromatase and PKB in the EXD-treated rats. EXD attenuated 17β-estradiol stimulated proliferation of breast cancer cells.ConclusionsThe results obtained from immunoblotting and measurements of serum estradiol level of the present investigation revealed that EXD may relieve the menopausal syndrome through an upregulation of ovarian aromatase and p-PKB expression without stimulating the growth of breast cancer cells.



http://ift.tt/2i4bIYV

Selaginella uncinata flavonoids ameliorated ovalbumin-induced airway inflammation in a rat model of asthma

Publication date: 4 January 2017
Source:Journal of Ethnopharmacology, Volume 195
Author(s): Bing Yu, Wei Cai, Huan-Huan Zhang, Yu-Sen Zhong, Jie Fang, Wen-You Zhang, Li Mo, Lu-Chen Wang, Chen-Huan Yu
Ethnopharmacological relevanceSelaginella uncinata (Desv.) Spring, known as "Cuiyuncao", is a perennial herb widely distributed in the Southeast Asian countries. In the folk medicine, the local minority commonly use it to treat cough and asthma for centuries.Aim of the studyThis study was carried out to investigate the protective mechanisms of total flavonoids from S. uncinata (SUF) on airway hyperresponsiveness, cytokine release and bitter taste receptors (T2Rs) signaling with emphasis on inflammatory responses in a rat model of ovalbumin (OVA)-induced asthma.Materials and methodsRats were sensitized and challenged with OVA to induce typical asthmatic reactions. Pathological changes of lung tissue were examined by HE staining. The serum levels of T cell-associated cytokines (IFN-γ, IL-4, IL-5 and IL-13), total IgE and OVA-specific IgE were determined by enzyme-linked immunosorbent assay (ELISA). Gene expressions of T2R10, IP3R1 and Orai1 in lung tissue were assayed by fluorescence quantitative real-time polymerase chain reaction (FQ-PCR) while protein expressions of NFAT1 and c-Myc were assayed by western blot analysis. The activation of SUF was investigated on tansgentic T2R10-GFP HEK293 cells.ResultsSUF treatment attenuated airway hyperresponsiveness and goblet cell hyperplasia compared with OVA-challenged asthmatic rats. The serum levels of IL-4, IL-5 and IL-13 as well as total and OVA-specific IgE were decreased while serum IFN-γ was increased in SUF-treated rats. SUF treatment significantly up-regulated T2R10 gene expression, down-regulated IP3R1 and Orai1 gene expression. SUF further suppressed eotaxin, NFAT1 and c-Myc protein expression in lung tissues of OVA-challenged rats.ConclusionsThese results imply that SUF exerts anti-inflammatory function through the T2R10/IP3R1/NFAT1 dependent signaling pathway, and may warrant further evaluation as a possible agent for the treatment of asthma.

Graphical abstract

http://ift.tt/2hjOCz1

Garcinia kola aqueous suspension prevents cerebellar neurodegeneration in long-term diabetic rat – a type 1 diabetes mellitus model

Publication date: 4 January 2017
Source:Journal of Ethnopharmacology, Volume 195
Author(s): Mohammed Farahna, Paul F. Seke Etet, Sayed Y. Osman, Kıymet K. Yurt, Naheed Amir, Lorella Vecchio, Isınsu Aydin, Yousef H. Aldebasi, Azimullah Sheikh, John C. Chijuka, Süleyman Kaplan, Abdu Adem
Ethnopharmacological relevanceThe development of compounds able to improve metabolic syndrome and mitigate complications caused by inappropriate glycemic control in type 1 diabetes mellitus is challenging. The medicinal plant with established hypoglycemic properties Garcinia kola Heckel might have the potential to mitigate diabetes mellitus metabolic syndrome and complications.Aim of the studyWe have investigated the neuroprotective properties of a suspension of G. kola seeds in long-term type 1 diabetes mellitus rat model.Materials and methodsWistar rats, made diabetic by single injection of streptozotocin were monitored for 8 months. Then, they were administered with distilled water or G. kola oral aqueous suspension daily for 30 days. Body weight and glycemia were determined before and after treatment. After sacrifice, cerebella were dissected out and processed for stereological quantification of Purkinje cells. Histopathological and immunohistochemical analyses of markers of neuroinflammation and neurodegeneration were performed.ResultsPurkinje cell counts were significantly increased, and histopathological signs of apoptosis and neuroinflammation decreased, in diabetic animals treated with G. kola compared to diabetic rats given distilled water. Glycemia was also markedly improved and body weight restored to non-diabetic control values, following G. kola treatment.ConclusionsThese results suggest that G. kola treatment improved the general condition of long-term diabetic rats and protected Purkinje cells partly by improving the systemic glycemia and mitigating neuroinflammation.

Graphical abstract

http://ift.tt/2hk03GO

Sulfur fumigation reducing systemic exposure of ginsenosides and weakening immunomodulatory activity of ginseng

Publication date: 4 January 2017
Source:Journal of Ethnopharmacology, Volume 195
Author(s): Bin Ma, Winnie Lai Ting Kan, He Zhu, Song-Lin Li, Ge Lin
Ethnopharmacological relevanceGinseng (Ginseng Radix et Rhizoma) is used worldwide for its miracle tonic effects, especially for its immunomodulatory activities. Sulfur fumigation, a fast and convenient method to prevent pesticidal and bacterial contamination in the food industry, has been recently employed during post-harvest processing of ginseng. Our previous studies demonstrated that sulfur fumigation significantly altered the chemical profile of the bioactive ingredients in ginseng. However, the effects of sulfur fumigation on the pharmacokinetics and bioactivities of ginseng remain unknown.Aim of the studyTo examine the effects of sulfur fumigation on the pharmacokinetics and immunomodulatory activities of ginseng.Materials and methodsFor pharmacokinetic studies, male Sprague-Dawley rats exposed to single/multiple dosages of non-fumigated ginseng (NFG) and sulfur fumigated ginseng (SFG) were investigated using HPLC-MS/MS analysis. For bioactivity studies, male ICR mice were used to compare the immunomodulatory effects of NFG or SFG under both normal and cyclophosphamide (CY)-induced immunocompromised conditions using white blood cell counts, serum cytokine levels, and spleen and thymus weight indices.ResultsSulfur fumigation significantly reduced the contents of the bioactive ginsenosides in ginseng, which resulted in drastically low systemic exposure of ginsenosides in SFG-treatment group compared to NFG-treatment group. This observation was consistent with the bioactivities obtained in NFG- and SFG-treatment groups. The bioactivity studies also demonstrated the immunomodulatory effects of NFG but not SFG in the CY-induced immunosuppressed mice.ConclusionSulfur fumigation significantly reduced contents of bioactive ginsenosides in ginseng, leading to dramatic decrease in the systemic exposure of these ginsenosides in the body and detrimental reduction of immunomodulatory effects of ginseng. Our results provided scientific evidences and laid a solid foundation for the needs of thorough evaluation of the significant impact of sulfur fumigation on ginseng and other medicinal herbs.

Graphical abstract

http://ift.tt/2hjXMve

Effects of aqueous extracts of Ecliptae herba, Polygoni multiflori radix praeparata and Rehmanniae radix praeparata on melanogenesis and the migration of human melanocytes

Publication date: 4 January 2017
Source:Journal of Ethnopharmacology, Volume 195
Author(s): Ping Xu, Shulan Su, Cheng Tan, Ren-Sheng Lai, Zhong-Sheng Min
Ethnopharmacological relevancePolygoni multiflori radix praeparata (PMRP), Ecliptae herba (EH) and Rehmanniae radix praeparata (RRP) are the most frequently-used herbs by Traditional Chinese Medicine practitioners for the treatment of vitiligo. Their abilities to stimulate melanogenesis, melanocyte migration and MITF (microphthalmia associated transcription factor) protein expression were evaluated in this study.Materials and methodsThe effects of aqueous extracts of PMRP, EH and RRP on human melanocytes in vitro were examined by MTT assay, tyrosinase activity, melanin synthesis, migration assay and Western blot.ResultsTreatment with EH (at 100μg/ml and 400μg/ml) significantly increased intracellular tyrosinase activity in accordance with the elevation of melanin content at the same concentrations. Treatment with RRP (at 100μg/ml and 400μg/ml) promoted melanin production but had no stimulatory effect on tyrosinase activity. Treatment with PMRP and EH (at 100μg/ml) promoted the migration of human melanocytes in a type IV collagen-coated transwell migration assay. Western blot analysis showed MITF protein expression was elevated by PMRP, EH and RRP (at 100μg/ml).ConclusionAn aqueous extract of EH has a synergistic effect on melanocytes by up-regulating tyrosinase activity, enhancing melanin synthesis and promoting melanocyte migration as well as elevating MITF protein expression. RRP exhibits a significant stimulating effect on melanogenesis and MITF protein expression. These results suggest that EH and RRP contain substances with direct enhancing effects on melanogenesis and migration, possibly via their effects on MITF protein expression.

Graphical abstract

http://ift.tt/2hjXN2g

Zanthoxylum piperitum reversed alveolar bone loss of periodontitis via regulation of bone remodeling-related factors

Publication date: 4 January 2017
Source:Journal of Ethnopharmacology, Volume 195
Author(s): Mi Hye Kim, Hye Ji Lee, Jung-Chul Park, Jongki Hong, Woong Mo Yang
Ethnopharmacological relevanceZanthoxylum piperitum (ZP) has been used to prevent toothache in East Asia.Aim of studyIn this study, we investigated the effects of ZP on periodontitis along with alveolar bone loss.Materials and methodsTwenty-eight male Sprague-Dawley rats were assigned into 4 groups; non-ligated (NOR), ligated and treated vehicle (CTR), ligated and treated 1mg/mL ZP (ZP1), and ligated and treated 100mg/mL ZP (ZP100). Sterilized 3-0 nylon ligature was placed into the subgingival sulcus around the both sides of mandibular first molar. After topical application of 1 and 100mg/mL ZP for 2 weeks, mandibles was removed for histology. In addition, SaOS-2 osteoblast cells were treated 1, 10 and 100μg/mL ZP for 24h to analyze the expressions of alveolar bone-related markers.ResultsSeveral alveolar bone resorption pits, which indicate cementum demineralization were decreased by ZP treatment. Topical ZP treatment inhibited periodontitis-induced alveolar bone loss. In addition, there were significant reduction of osteoclastic activities following topical ZP treatment in periodontium. The expression of RANKL was decreased in SaOS-2 osteoblast cells by treating ZP, while that of OPG was increased. ZP treatment increased the expressions of Runx2 and Osterix in SaOS-2 cells.ConclusionIn summary, ZP treatment inhibited alveolar bone loss as well as maintained the integrity of periodontal structures via regulation of bone remodeling. ZP may be a therapeutic target for treating periodontitis.

Graphical abstract

http://ift.tt/2hk8gdZ

Protective effects and mechanisms investigation of Kuntai capsule on the ovarian function of a novel model with accelerated aging ovaries

Publication date: 4 January 2017
Source:Journal of Ethnopharmacology, Volume 195
Author(s): Jinjin Zhang, Li Fang, Liangyan Shi, Zhiwen Lai, Zhiyong Lu, Jiaqiang Xiong, Meng Wu, Aiyue Luo, Shixuan Wang
Ethnopharmacological relevanceKuntai capsule, a traditional Chinese medicine, has been widely used for the clinical treatment of menopausal syndrome. However, its mechanisms remain poorly understood. Considering that aging ovaries are the primary cause of menopause, this study was designed to investigate the effects and mechanisms of Kuntai capsule on ovarian function in a novel mice model with accelerated aging ovaries.Materials and methodsSeventy-five female C57BL/6 mice were chosen for this study. Fifteen of the mice were separated into the normal control group (NC). The remaining sixty were used to establish the novel accelerated aging ovary model by superovulation and oxidative stress and then by randomly dividing the mice into four equal groups. One group was considered the model group (Mod). The other three groups were treated with low (0.4g/kg), middle (0.8g/kg) and high (1.6g/kg) doses of Kuntai capsule intragastrically every day for 4 weeks. During the treatment, the body weight and fur condition of all mice were recorded. All the mice were forced to swim to record their exhaustive swimming time (EST), which measures their strength. Mice were then sacrificed for sampling. Ovarian reserve was evaluated using follicle counts and AMH expression. Ovarian function was evaluated using estrous cycle, sex hormone level and litter experiments. Ovarian follicles were categorized and counted to estimate ovarian reserve, and ovarian histologic sections were stained for terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) to detect apoptotic cells. The ultrastructure of ovarian cells was observed using transmission electron microscopy. Western blotting was used to measure expression of Bax, Bcl2, AMH and SOD2 protein.ResultsCompared with the NC GROUP, the Mod group clearly displayed worse fur condition and ovarian function. These situations showed some improvement after Kuntai capsule treatment. Specifically, the fur condition and the EST of the Kuntai capsule groups were superior to the fur condition and EST of the Mod group. In cases of damaged ovarian function, Kuntai capsule can regulate the estrous cycles, increase hormone secretion and fertility and significantly decrease atretic follicles. The transmission electron microscopy results revealed that Kuntai capsule rescued the ovarian ultrastructure of mice. TUNEL staining confirmed that the apoptotic cells were reduced after Kuntai capsule treatment. Western blotting revealed that Kuntai capsule can increase AMH, SOD2, and Bcl2 protein expression and decrease Bax expression.ConclusionsKuntai capsule may improve damaged ovarian function, which may be related to its antioxidant and anti-apoptosis effects.

Graphical abstract

http://ift.tt/2hk3dKN

The effects of herbal composition Gambigyeongsinhwan (4) on hepatic steatosis and inflammation in Otsuka Long‐Evans Tokushima fatty rats and HepG2 cells

Publication date: 4 January 2017
Source:Journal of Ethnopharmacology, Volume 195
Author(s): Seolah Yoon, Jeongjun Kim, Hyunghee Lee, Haerim Lee, Jonghoon Lim, Heejeong Yang, Soon Shik Shin, Michung Yoon
Ethnopharmacological relevanceHepatic steatosis has risen rapidly in parallel with a dramatic increase in obesity. The aim of this study was to determine whether the herbal composition Gambigyeongsinhwan (4) (GGH(4)), composed of Curcuma longa L. (Zingiberaceae), Alnus japonica (Thunb.) Steud. (Betulaceae), and the fermented traditional Korean medicine Massa Medicata Fermentata, regulates hepatic steatosis and inflammation.Materials and methodsThe effects of GGH(4) on hepatic steatosis and inflammation in Otsuka Long-Evans Tokushima fatty (OLETF) rats and HepG2 cells were examined using Oil red O, hematoxylin and eosin, and toluidine blue staining, immunohistochemistry, quantitative real-time polymerase chain reaction, and peroxisome proliferator-activated receptor α (PPARα) transactivation assay.ResultsAdministration of GGH(4) to OLETF rats improved hepatic steatosis and lowered serum levels of alanine transaminase, total cholesterol, triglycerides, and free fatty acids. GGH(4) increased mRNA levels of fatty acid oxidation enzymes (ACOX, HD, CPT-1, and MCAD) and decreased mRNA levels of lipogenesis genes (FAS, ACC1, C/EBPα, and SREBP-1c) in the liver of OLETF rats. In addition, infiltration of inflammatory cells and expression of inflammatory cytokines (CD68, TNFα, and MCP-1) in liver tissue were reduced by GGH(4). Treatment of HepG2 cells with a mixture of oleic acid and palmitoleic acid induced significant lipid accumulation, but GGH(4) inhibited lipid accumulation by regulating the expression of hepatic fatty acid oxidation and lipogenic genes. GGH(4) also increased PPARα reporter gene expression. These effects of GGH(4) were similar to those of the PPARα activator fenofibrate, whereas the PPARα antagonist GW6471 reversed the inhibitory effects of GGH(4) on lipid accumulation in HepG2 cells.ConclusionsThese results suggest that GGH(4) inhibits obesity-induced hepatic steatosis and that this process may be mediated by regulation of the expression of PPARα target genes and lipogenic genes. GGH(4) also suppressed obesity-related hepatic inflammation. Thus, GGH(4) may be a promising drug for the treatment of obesity-related liver diseases.

Graphical abstract

http://ift.tt/2hjRThM

Secondary metabolites from Tetracera potatoria stem bark with anti-mycobacterial activity

Publication date: 4 January 2017
Source:Journal of Ethnopharmacology, Volume 195
Author(s): M.C.Y. Fomogne-Fodjo, D.T. Ndinteh, D.K. Olivier, P. Kempgens, S. van Vuuren, R.W.M. Krause
Ethnopharmacological relevanceTetracera potatoria Afzel. Exg. Don (Dilleniaceae) is a medicinal plant used traditionally in Africa for the treatment of tuberculosis related ailments and respiratory infections. The antibacterial activity of the medium polar extracts of T. potatoria leaves and stem bark was recently reported against Mycobacterium smegmatis (MIC 25µg/mL) and M. aurum (65µg/mL), two fast-growing Mycobacterium strains used as model micro-organisms for the more pathogenic strain Mycobacterium tuberculosis (Fomogne-Fodjo et al., 2014). The aim of this study was consequently to isolate the compounds possibly contributing to this activity, and which may therefore be promising precursors to be used for the development of novel anti-TB drugs.Materials and methodsT. potatoria medium polar extract [MeOH/DCM (1:1, v/v)] was fractionated sequentially with petroleum ether to which EtOAC and MeOH were gradually added to increase the polarity. The examination of T. potatoria extract and its fractions was guided by bioassays for anti-mycobacterial activity against M. smegmatis (ATCC 23246) and M. aurum (NCTC 10437) using the minimum inhibitory concentration (MIC) method. All the isolated compounds were structurally elucidated using spectroscopic techniques and evaluated for their anti-mycobacterial activity.ResultsTwo novel secondary metabolites (1, 2) named tetraceranoate and N-hydroxy imidate-tetracerane, together with five known compounds [β-stigmasterol (3), stigmast-5-en-3β-yl acetate (4), betulinic acid (5), betulin (6) and lupeol (7)] were isolated and identified. Tetraceranoate exhibited the best activity against M. smegmatis with a minimum inhibitory concentration (MIC) of 7.8µg/mL, while β-stigmasterol, betulinic acid and betulin showed appreciable anti-mycobacterial activity against both strains (MIC 15µg/mL).ConclusionSeven compounds were isolated from the medium polar extract [MeOH/DCM (1:1, v/v)] of T. potatoria stem bark. Only tetraceranoate one of the isolated compounds showed antibacterial activity against M. smegmatis having efficacy as high as rifampicin (one of a three drug regimen recommended in the initial phase short-course anti-tuberculosis therapy). Thus, tetraceranoate might be an interesting target for systematic testing of anti-TB treatment and management. This research supports the use of T. potatoria in African traditional medicine for the treatment of tuberculosis related symptoms.

Graphical abstract

http://ift.tt/2hjSyja

Chenopodium album Linn. leaves prevent ethylene glycol-induced urolithiasis in rats

Publication date: 4 January 2017
Source:Journal of Ethnopharmacology, Volume 195
Author(s): Indu Sikarwar, Yadu Nandan Dey, Manish M. Wanjari, Ajay Sharma, Sudesh N. Gaidhani, Ankush D. Jadhav
Ethnopharmacological relevanceThe leaves of Chenopodium album Linn. are traditionally used for correction of kidney diseases and urinary stones. The present work investigated the effect of methanolic and aqueous extracts of leaves of Chenopodium album on experimentally-induced urolithiasis in rats to substantiate its traditional use as antilithiatic agent.Materials and methodsThe leaf extract was standardized by HPLC. Urolithiasis was induced in rats by administration of 0.75% v/v of ethylene glycol (EG) in distilled water and in addition, vehicle or methanol (CAME) or aqueous (CAAE) extract of the leaves of Chenopodium album each in the dose 100, 200 and 400mg/kg or Cystone (750mg/kg) were administered daily orally for 28 days. Urolithiasis was assessed by estimating the calcium, phosphorus, urea, uric acid, and creatinine in both urine and plasma. The volume, pH and oxalate levels were also estimated in urine. The renal oxalate content was estimated in kidney while calcium oxalate deposits were observed histologically.ResultsThe treatment with CAME or CAAE for 28 days significantly attenuated the EG-induced elevations in the urine and plasma levels of calcium, phosphorus, urea, uric acid and creatinine along with decrease in urine volume, pH and oxalates. The treatments also decreased renal tissue oxalate and deposition of oxalate crystals in kidney due to EG treatment. The effects of CAME and CAAE were comparable to standard antilithiatic agent, cystone. The findings indicate the preventive effect of CAME and CAAE which can be due to inhibitory effect on crystallization and stone dissolution. The effect was attributed to the presence of phytochemicals like flavonoids and saponins.ConclusionIn conclusion, Chenopodium album leaves exhibited antilithiatic effect and validates its ethnomedicinal use in urinary disorders and kidney stones.

Graphical abstract

http://ift.tt/2hjWkcm

Clinicopathologic analysis of atypical hand, foot, and mouth disease in adult patients

Hand, foot, and mouth disease is a contagious viral infection usually affecting children. A resurgence of cases in adults, mainly caused by coxsackievirus A6 and with an atypical and more severe presentation, has taken place.

http://ift.tt/2hjScsI

Neuroprotective effects of 2,3,5,4′-tetrahydoxystilbene-2-O-β-D-glucoside from Polygonum multiflorum against glutamate-induced oxidative toxicity in HT22 cells

Publication date: 4 January 2017
Source:Journal of Ethnopharmacology, Volume 195
Author(s): Sun Young Lee, Sung Min Ahn, Ziyu Wang, Young Whan Choi, Hwa Kyoung Shin, Byung Tae Choi
Ethnopharmacological relevanceSince ancient times, Polygonum multiflorum Thunb. has been used to treat premature grey hair, dizziness, and blurred vision in East Asia. A major bioactive constituent of this medicinal herb, 2,3,5,4'-tetrahydoxystilbene-2-O-β-D-glucoside (THSG), has antioxidant activity and exerts beneficial effects on cognition and memory.Aim of the studyThe purpose of the current study was to determine if THSG affects hippocampal neuronal cell death and mitochondrial function following exposure to oxidative stress.Materials and methodsHT22 hippocampal cells with or without THSG pretreatment were exposed to glutamate, and the effects on cell viability and expression of molecules related to apoptotic cell death were examined using biochemical techniques, flow cytometry, western immunoblotting, and real-time polymerase chain reaction.ResultsPretreatment with THSG significantly attenuated glutamate-induced loss of cell viability and release of lactate dehydrogenase as well as apoptotic cell death. THSG inhibited generation of reactive oxygen species (ROS), expression of heme oxygenase-1, and activation of caspase-3 and calpain-1 proteases, all of which were increased by glutamate. THSG inhibited glutamate-induced disruption of mitochondrial membrane potential (MMP) and voltage-dependent anion channel-1. It also regulated the ratio of Bax to Bcl-2.ConclusionsThese results indicate that THSG has a marked neuroprotective effect against glutamate-induced hippocampal damage by decreasing ROS production and stabilizing MMP. These findings suggest the potential of THSG as a new therapeutic agent for the treatment of cognitive disorders.

Graphical abstract

http://ift.tt/2hjRV98

Inflammatory bowel disease among patients with psoriasis treated with ixekizumab: A presentation of adjudicated data from an integrated database of 7 randomized controlled and uncontrolled trials

Inflammatory bowel disease (IBD) occurs more frequently in patients with psoriasis. The 2 diseases have significant genetic overlap, but the pathogenesis underlying their co-occurrence is unknown.

http://ift.tt/2hdDXTg

Analgesic effect of coumarins from Radix angelicae pubescentis is mediated by inflammatory factors and TRPV1 in a spared nerve injury model of neuropathic pain

Publication date: 4 January 2017
Source:Journal of Ethnopharmacology, Volume 195
Author(s): Ruili Li, Chao Zhao, Minna Yao, Ying Song, Yin Wu, Aidong Wen
Ethnopharmacological relevanceCoumarins from Radix angelicae pubescentis (CRAP) are a major active component that are isolated from dried roots of Angelica biserrata Yuan et Shan, which has been used clinically to cure headaches for a long period of time, and it is an effective treatment for pain. The aim of the present study was to investigate the analgesic effect of CRAP on a spared nerve injury (SNI) model of neuropathy.Materials and methodsAntinociceptive effects of CRAP were assessed in Sprague-Dawley male rats using a spared nerve injury model of neuropathic pain. Inflammatory factors were determined by Enzyme-linked immunosorbent assay (ELISA). Transient receptor potential cation channel 1 (TRPV1) and Phosphorylated extracellular regulated protein kinases (pERK) were detected by Immunofluorescence and Western blotting, respectively.ResultsThe high performance liquid chromatography (HPLC) analysis showed the presence of osthole and columbianadin in Radix angelicae pubescentis. CRAP induced the dose-dependent effect of on attenuating the development of mechanical hypersensitivity. Molecular profiling revealed that CRAP reduced the levels of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) and significantly attenuated the expression of TRPV1 and pERK in damaged DRG neurons.ConclusionThis results demonstrate that CRAP possess remarkable antinociceptive activities which may be due to osthole and columbianadin at least in part, supporting the folkloric usage of the plant to treat various pain diseases.

Graphical abstract

http://ift.tt/2hjUeJi

Recurrence of moderately dysplastic nevi with positive histologic margins

The Pigmented Lesion Subcommittee of the Melanoma Prevention Working Group recently published a consensus statement that incompletely excised moderately dysplastic nevi (MDN) without clinical residual pigmentation can be observed and not re-excised. However, data regarding recurrence of MDN with positive histologic margins are quite scant.

http://ift.tt/2i4kd6B

Is there nothing new under the sun? The influence of herbals and pharmacopoeias on ethnobotanical traditions in Albacete (Spain)

Publication date: 4 January 2017
Source:Journal of Ethnopharmacology, Volume 195
Author(s): Diego Rivera, Alonso Verde, Concepción Obón, Francisco Alcaraz, Candelaria Moreno, Teresa Egea, José Fajardo, José Antonio Palazón, Arturo Valdés, Maria Adele Signorini, Piero Bruschi
Ethnopharmacological relevanceThis paper has two overarching aims: (1) presenting the results of studying the Albacete tariff of medicines of 1526 and (2) broadly analyzing the origin and influences of medicinal traditional knowledge in the region of Albacete, Spain. We use historical and modern literature that may have influenced this knowledge. Our primary goal was to determine the ingredients used in the pharmacy in the 16th century CE in Albacete through the analysis of the tariff, and our secondary goal was to investigate until when ingredients and uses present in pharmacy and herbals persisted in later periods.MethodsThe identity of medicines and ingredients was determined by analyzing contemporary pharmacopoeias and classical pharmaceutical references. We analyzed further 21 sources (manuscripts, herbals, and books of medicines, pharmacopoeias, pharmacy inventories, and modern ethnobotanical records) for the presence/absence of ingredients and complex formulations of the tariff. Using factorial and cluster analysis and Bayesian inference applied to evolution models (reversible-jump Markov chain Monte Carlo), we compared textual sources. Finally, we analyzed the medicinal uses of the top 10 species in terms of frequency of citation to assess the dependence of modern ethnobotanical records on Renaissance pharmacy and herbals, and, ultimately, on Dioscorides.ResultsIn Albacete 1526, we determined 101 medicines (29 simple drugs and 72 compound medicines) comprising 187 ingredients (85% botanical, 7.5% mineral, and 7.5% zoological substances). All composed medicines appear standardized in the pharmacopoeias, notably in the pharmacopoeia of Florence from 1498. However, most were no longer in use by 1750 in the pharmacy, and were completely absent in popular herbal medicine in Albacete 1995 as well as in Alta Valle del Reno (Italy) in 2014. Among the ingredients present in different formulation are the flowers of Rosa gallica, honey (Apis mellifera), the roots of Nardostachys jatamansi, and Convolvulus scammonia, pistils of Crocus sativus, grapes and raisins (Vitis vinifera), rhizomes of Zingiber officinale, bark of Cinnamomum verum, leaves and fruits of Olea europaea, mastic generally of Pistacia lentiscus, and wood of Santalum album. The statistical analysis of sources produces four well-separated clusters (Renaissance Herbals and Pharmacopoeias, Ethnobotany and Folk Medicine, Old phytotherapy, and Modern phytotherapy including Naturopathy) confirming our a priori classification. The clade of Renaissance Herbals and Pharmacopoeias appears separated from the rest in 97% of bootstrapped trees. Bayesian inference produces a tree determined by an initial set of two well-distinct core groups of ingredients: 64, locally used in Mediterranean Europe during centuries; and 45, imported, used in pharmacy during centuries. Complexity reached its maximum in Albacete 1526 and contemporary pharmacopoeias, gradually decreasing over time. The analysis of medicinal uses of the top 10 ingredients showed low coincidence between Dioscorides and different Renaissance herbals or medical treatises and of all of them with ethnobotany in Albacete.ConclusionsRegarding our question: is there something new under the sun? In some aspects, the answer is "No". The contrast between expensive drugs, highly valued medicines, and unappreciated local wild medicinal plants persists since the Salerno's school of medicine. Old medicine in Mediterranean Europe, as reflected by Albacete 1526 tariff of medicines, involved strict formulations and preferences for certain ingredients despite other ingredients locally available but underappreciated. This confirms the fact that any system of medicine does not get to use all available resources. Ethnobiological records of materia medica, in rural areas of Albacete, describe systems with a high degree of stability and resilience, where the use of local resources, largely wild but also cultivated, is predominant in contrast with the weight of imported exotic products in pharmacy.

Graphical abstract

http://ift.tt/2hjSy2E

Transcriptome inference and systems approaches to polypharmacology and drug discovery in herbal medicine

Publication date: 4 January 2017
Source:Journal of Ethnopharmacology, Volume 195
Author(s): Peng Li, Jianxin Chen, Wuxia Zhang, Bangze Fu, Wei Wang
Ethnopharmacological relevanceHerbal medicine is a concoction of numerous chemical ingredients, and it exhibits polypharmacological effects to act on multiple pharmacological targets, regulating different biological mechanisms and treating a variety of diseases. Thus, this complexity is impossible to deconvolute by the reductionist method of extracting one active ingredient acting on one biological target.Aim of the studyTo dissect the polypharmacological effects of herbal medicines and their underling pharmacological targets as well as their corresponding active ingredients.Materials and methodsWe propose a system-biology strategy that combines omics and bioinformatical methodologies for exploring the polypharmacology of herbal mixtures. The myocardial ischemia model was induced by Ameroid constriction of the left anterior descending coronary in Ba-Ma miniature pigs. RNA-seq analysis was utilized to find the differential genes induced by myocardial ischemia in pigs treated with formula QSKL. A transcriptome-based inference method was used to find the landmark drugs with similar mechanisms to QSKL.ResultsGene-level analysis of RNA-seq data in QSKL-treated cases versus control animals yields 279 differential genes. Transcriptome-based inference methods identified 80 landmark drugs that covered nearly all drug classes. Then, based on the landmark drugs, 155 potential pharmacological targets and 57 indications were identified for QSKL.ConclusionOur results demonstrate the power of a combined approach for exploring the pharmacological target and chemical space of herbal medicines. We hope that our method could enhance our understanding of the molecular mechanisms of herbal systems and further accelerate the exploration of the value of traditional herbal medicine systems.

Graphical abstract

http://ift.tt/2hjUfNm

Eurycoma longifolia as a potential alternative to testosterone for the treatment of osteoporosis: Exploring time-mannered proliferative, differentiative and morphogenic modulation in osteoblasts

Publication date: 4 January 2017
Source:Journal of Ethnopharmacology, Volume 195
Author(s): Hnin Ei Thu, Isa Naina Mohamed, Zahid Hussain, Ahmad Nazrun Shuid
Ethnopharmacological relevanceEurycoma longifolia (EL) has been well-studied traditionally as a chief ingredient of many polyherbal formulations for the management of male osteoporosis. It has also been well-recognised to protect against bone calcium loss in orchidectomised rats.Aim of the studyTo evaluate the effects of EL on the time-mannered sequential proliferative, differentiative, and morphogenic modulation in osteoblasts compared with testosterone.Materials and methodsCell proliferation was analysed using MTS assay and phase contrast microscopy. Osteogenic differentiation of MC3T3-E1 cells was assessed through a series of characteristic assays which include crystal violet staining, alkaline phosphatase (ALP) activity and Van Gieson staining. Taken together, the bone mineralization of extra cellular matrix (ECM) was estimated using alizarin red s (ARS) staining, von kossa staining, scanning electron microscopic (SEM) and energy dispersive x-ray (EDX) analysis.ResultsThe cell proliferation data clearly revealed the efficiency of EL particularly at a dose of 25µg/mL, in improving the growth of MC3T3-E1 cells compared with the untreated cells. Data also showed the prominence of EL in significantly promoting ALP activity throughout the entire duration of treatment compared with the testosterone-treated cells. The osteogenic differentiation potential of EL was further explored by analysing mineralization data which revealed that the calcified nodule formation (calcium deposition) and phosphate deposition was more pronounced in cells treated with 25µg/mL concentration of EL at various time points compared with the untreated and testosterone treated cells. The scanning electron microscopic (SEM) analysis also revealed highest globular masses of mineral deposits (identified as white colour crystals) in the ECM of cultured cells treated with 25µg/mL concentration of EL.ConclusionCompared to testosterone, greater potential of EL in promoting the proliferation and osteogenic differentiation of MC3T3-E1 cells provides an in vitro basis for the prevention of male osteoporosis. Thus, we anticipate that EL can be considered as an alternative approach to testosterone replacement therapy (TRT) for the treatment of male osteoporosis.

Graphical abstract

http://ift.tt/2hjVlsH

Bioactive alkaloids from the aerial parts of Houttuynia cordata

Publication date: 4 January 2017
Source:Journal of Ethnopharmacology, Volume 195
Author(s): Qinge Ma, Rongrui Wei, Zhiqiang Wang, Wenmin Liu, Zhipei Sang, Yaping Li, Hongchun Huang
Ethnopharmacological relevanceHouttuynia cordata is an important traditional Chinese medicine used in heat-clearing and detoxifying, swelling and discharging pus, promoting diuresis and relieving stranguria which recorded in Pharmacopoeia of the people's Republic of China (2015 Edition). H. cordata has been recorded in the book Bencaogangmu which was written by Shizhen Li for the treatment of pyretic toxicity, carbuncle swelling, haemorrhoids, and rectocele diseases.Aim of the studyPhytochemical investigation of the aerial parts of H. cordata and evaluation of their PTP1B inhibitory activities and hepatoprotective activities.Materials and methodsThe dried aerial parts of H. cordata were fractionated by liquid-liquid extraction to obtain CHCl3, ethyl acetate, and n-butanolic fractions. The CHCl3 fraction was confirmed active fraction by the bioactivity-guided investigation, which was isolated and purified by chromatographing over silica gel, Sephadex LH-20, MPLC, and preparative HPLC. The chemical structures of the purified compounds were identified by their spectroscopic data and references.ResultsEight new compounds (1–8), together with fourteen known compounds (9–22) were isolated from the aerial parts of H. cordata. The known compounds (9–22) were obtained from this plant for the first time. Among them, some compounds exhibited moderate bioactivities.ConclusionCompounds (1–8) were identified as new alkaloids, and the known alkaloids (9–22) were isolated from this plant for the first time. Compounds 1, 4, 14, and 19 showed significant PTP1B inhibitory activities with IC50 values of 1.254, 2.016, 2.672, and 1.862µm, respectively. Compounds 1, 3, 6, 11, 17, and 20 (10µm) exhibited moderate hepatoprotective activities against D-galactosamine-induced WB-F344 cells damage.

Graphical abstract

http://ift.tt/2hjV6xE

Antianxiety activity guided isolation and characterization of bergenin from Caesalpinia digyna Rottler roots

Publication date: 4 January 2017
Source:Journal of Ethnopharmacology, Volume 195
Author(s): Jitender Singh, Ashwani Kumar, Anupam Sharma
Ethnopharmacological relevanceCaesalpinia digyna Rottler (Caesalpiniaceae) roots have been used traditionally for soothing nerves, as nervine tonic and febrifuge. The aim of the present study was to isolate the antianxiety constituent(s) from C. digyna roots following bioactivity guided fractionation approach.Material and methodsBioactive fraction F4 was subjected to column chromatography to get three sub-fractions (F4.1–F4.3) and a compound CD2. CD1 and CD2 were characterized using standard spectral techniques. Three fractions (F4.1–F4.3) were evaluated for antianxiety activity in mice using EPM. An effective dose of the antianxiety principle was optimized, and its activity was, further evaluated using open field and mirror chamber tests.ResultsCD1 and CD2 characterized as bergenin, exhibited significant antianxiety activity at 80mg/kg, po which was statistically comparable to that of diazepam (2mg/kg, po). However, F4.1-F4.3 were observed to be devoid of antianxiety activity. Bergenin also exhibited significant antianxiety activity in open field and mirrored chamber tests.ConclusionsBergenin, isolated from roots of C. digyna, exhibits significant antianxiety activity at 80mg/kg, po in three different models for evaluating antianxiety activity. This activity of bergenin is being reported for the first time.

Graphical abstract

http://ift.tt/2hjPbZI

Squill Oxymel, a traditional formulation from Drimia Maritima (L.) Stearn, as an add-on treatment in patients with moderate to severe persistent asthma: A pilot, triple-blind, randomized clinical trial

Publication date: 20 January 2017
Source:Journal of Ethnopharmacology, Volume 196
Author(s): Fatemeh Nejatbakhsh, Hossein Karegar-Borzi, Gholamreza Amin, Alireza Eslaminejad, Mostafa Hosseini, Mahbubeh Bozorgi, Mehrnaz Asadi Gharabaghi
Ethnopharmacological relevanceIn Traditional Iranian Medicine (TIM), Squill (Drimia maritima (L.) Stearn) Oxymel was utilized in the treatment of asthma. Squill has been reported to exert anti-inflammatory, anti-oxidant, anti-cholinergic, and mucus secretion modulating effects.ObjectiveThis study aimed to make a preliminary evaluation of the efficacy and safety of an add-on Squill Oxymel treatment in patients with moderate to severe persistent asthma.MethodsIn a 6-week, triple-blind, randomized, placebo-controlled trial, 60 patients with stable moderate to severe persistent asthma were randomly allocated to receive either 10ml syrup of Squill Oxymel, simple oxymel, or a placebo 2 times a day, as an add-on to their routine treatment (inhaled corticosteroids and β2 agonists). Spirometry and plethysmography were performed on patients to evaluate the effect of the treatment at baseline and end of intervention. Forced Expiratory Volume in first second (FEV1) was considered the primary outcome. St. George's respiratory questionnaire (SGRQ) was also used for the subjective evaluation of patients' responses.ResultsFifty-four patients completed the study. The results showed significant improvement in spirometry parameters, especially FEV1 (1.54±.38 vs. 2.11±.49l), in the Squill Oxymel group compared with the other groups. The increases in FEV1 liter, FEV1%, FEV1/FVC%, and MEF 25–75% during the intervention were significantly higher in the Squill Oxymel group than in the other groups (p<.001). However, the improvement of plethysmographic parameters showed no significant difference between the study groups (p>.05). The SGRQ scores (symptoms, activity, and total score) were significantly improved after intervention in both the Squill Oxymel and the simple honey oxymel groups (p<.001), but not in the placebo group. Nausea and vomiting was reported in 5 patients in Squill oxymel and simple oxymel groups. No other serious adverse event was observed.ConclusionsThe results of the current study show preliminary evidence for the efficacy and safety of the add-on treatment of Squill Oxymel in patients with moderate to severe persistent asthma.

Graphical abstract

http://ift.tt/2hjRRWY

Virtual reconstruction of midface defects using statistical shape models

This study evaluates the accuracy of a statistical shape model (SSM) for virtual fracture reconstruction of the lateral midface.

http://ift.tt/2iePUcT

Bioactive polysaccharide-based pH-sensitive polymers for cytoplasmic delivery of antigen and activation of antigen-specific immunity

Publication date: March 2017
Source:Biomaterials, Volume 120
Author(s): Eiji Yuba, Ayaka Yamaguchi, Yuta Yoshizaki, Atsushi Harada, Kenji Kono
For establishment of cancer immunotherapy, antigen carriers are needed which have functions not only to deliver antigen into cytosol of dendritic cells (DCs), which induces antigen-specific cellular immune responses, but also to activate DCs. We previously reported cytoplasmic delivery of antigen using liposomes modified with pH-sensitive polymers such as carboxylated poly(glycidol)s or dextran. Modification using these polymers provides stable liposomes with pH-sensitive fusogenic/membrane-disruptive ability. For this study, bioactive polysaccharide-based pH-sensitive polymers were constructed to achieve not only cytoplasmic delivery of antigen but also activation of DCs. Curdlan and mannan were used as bioactive polysaccharides because they are known to activate DCs via their respective interactions with Dectin-1 and Dectin-2. Carboxylated curdlan and mannan promoted Th1 cytokine production from DCs, indicating the activation of DCs by these polysaccharide derivatives. These polymer-modified liposomes released their contents at weakly acidic pH and delivered model antigenic proteins into cytosol of DCs. Subcutaneous administration of curdlan derivative-modified or mannan derivative-modified liposomes induced strong antigen-specific immune responses and stronger antitumor effects than those of liposomes modified with dextran derivative. Therefore, bioactive polysaccharide-modified liposomes that achieve both cytoplasmic delivery of antigen and activation of DCs are promising for cancer immunotherapy.



http://ift.tt/2isvfl6

A single fluorescent probe enables clearly discriminating and simultaneously imaging liquid-ordered and liquid-disordered microdomains in plasma membrane of living cells

Publication date: March 2017
Source:Biomaterials, Volume 120
Author(s): Minggang Tian, Yong Liu, Yuming Sun, Ruoyao Zhang, Ruiqing Feng, Ge Zhang, Lifang Guo, Xuechen Li, Xiaoqiang Yu, Jing Zhi Sun, Xiuquan He
Liquid-ordered (Lo) and liquid-disordered (Ld) microdomains in plasma membrane play different yet essential roles in various bioactivities. However, discrimination of the two microdomains in living cells is difficult, due to the similarity in their constituents and structures. Up to now, polarity sensitive probes are the only tool for imaging the two microdomains, but their small difference between emission spectra in the two microdomains (less than 50 nm) limited their application in living cells. In this work, we first presented an aggregation/monomer type of fluorescent probe (2,7-9E-BHVC12) with much larger separation in emission wavelength (up to 100 nm), for dual-color visualizing the two membrane microdomains in living cells. The probe can form red-emissive aggregates and yellow-emissive monomers when induced by Lo and Ld microdomains, respectively, and thus enables clear visualization of the two membrane microdomains in living cells with dual colors, and thus high-fidelity images of substructures of plasma membrane have been obtained. According to the images of three kinds of normal cells and three kinds of cancer cells stained with 2,7-9E-BHVC12, significant difference in plasma membrane microstructure of cancer cells was found. In terms of 2,7-9E-BHVC12, normal cells were mainly consisted of either Lo or Ld microdomains all over their membranes, while cancer cells all clearly display coexistence of Lo and Ld membrane microdomains. Therefore, 2,7-9E-BHVC12 can serve as a powerful tool for studies of membrane microdomains, and the different results of normal and cancer cells would also deepen our understanding in cancer science.



http://ift.tt/2hVflmh

A recombinant vesicular stomatitis virus encoding CCR5-tropic HIV-1 receptors targets HIV-1-infected cells and controls HIV-1 infection

Publication date: Available online 24 December 2016
Source:Microbes and Infection
Author(s): Kazu Okuma, Koji Fukagawa, Takuya Kohma, Youichi Takahama, Yukio Hamaguchi, Mamoru Ito, Yuetsu Tanaka, Linda Buonocore, John K. Rose, Isao Hamaguchi
Anti-retroviral therapy is useful to treat human immunodeficiency virus type 1 (HIV-1)-infected individuals, but has some major problems, such as the generation of multidrug-resistant viruses. To develop a novel supplemental or alternative therapeutic for CCR5-tropic (R5) HIV-1 infection, we generated a recombinant vesicular stomatitis virus (rVSV) in which the gene encoding its envelope glycoprotein (G) was replaced with the genes encoding R5 HIV-1 receptors (human CD4 and CCR5), designated VSVΔG-CC5. Our present data demonstrate that this rVSV specifically infects cells that are transiently expressing R5 HIV-1 envelope glycoproteins, but does not infect those expressing CXCR4-tropic HIV-1 envelope glycoproteins. Notably, after a CD4⁺CCR5⁺ T cell line or primary cells initially infected with R5 HIV-1 were inoculated with G-complemented VSVΔG-CC5, the rVSV significantly reduced the number of HIV-1-infected cells, probably through direct targeting of the rVSV and VSV-mediated cytolysis and/or through syncytium formation- or cell-cell fusion-dependent killing, and markedly inhibited HIV-1 production. Furthermore, G-complemented VSVΔG-CC5 also efficiently inhibited HIV-1 infection in R5 HIV-1-infected humanized immunodeficient mice. Taken together, our findings indicate that a cytolytic rVSV that targets and eliminates R5 HIV-1-infected cells potentially has therapeutic value for controlling R5 HIV-1 infection.



http://ift.tt/2hdwjIe

Rat model of chronic tympanic membrane perforation: A longitudinal histological evaluation of underlying mechanisms

To evaluate histologically the progressive development and underlying mechanisms of chronic tympanic membrane perforation (TMP) in a rat model using a two-weeks ventilation tube (VT) treatment combined with topical application of mitomycin C/dexamethasone (VT-M/D), compared with normal tympanic membrane and acute TMPs.

http://ift.tt/2hjUDf6

Corrigendum to “Oral microbiome, periodontitis and risk of head and neck cancer” [Oral Oncol. 53 (2016) 17–19]

The authors regret the error published on Page 17, Line 8. Please note the corrected statement: "Still, germ-free rats presented with lower acetaldehyde concentration, indicating that might exist a link between poor oral hygiene, alcohol consumption and increased risk of OCC [2,6]".

http://ift.tt/2hDzkTx

The ATA wishes you a Happy Holiday Season

Season's Greetings to all our Friends of the ATA

The post The ATA wishes you a Happy Holiday Season appeared first on American Thyroid Association.

http://ift.tt/2hdlCp8

GG decreases in vitro digestive lipolysis and carotenoid bioaccessibility from a pre-formed protein-stabilized emulsion

Publication date: Available online 24 December 2016
Source:Bioactive Carbohydrates and Dietary Fibre
Author(s): Jamal Amyoony, Xinjie Lin, Amanda Joyce Wright
Guar gum (GG) is a viscosity-inducing soluble dietary fibre used to thicken and stabilize foods and which may impact nutrient digestion and absorption. This research was undertaken to investigate the impact of GG (0.0 1.0, 1.5, 2.0, or 4.0% (w/v)) on lipid digestibility using an in vitro model of upper gastrointestinal digestion. Canola oil-in-water emulsions containing 0.1% beta-carotene (BC) were prepared and free fatty acid release and BC bioaccessibility under simulated duodenal conditions determined. The presence of GG increased digestate viscosity and the highest concentration investigated was associated with attenuated lipolysis and BC bioaccessibility. There were no differences in particle size or zeta-potential to suggest interfacial activity and minimal differences observed in digestate aqueous phase bile acid concentration. The results point to viscosity mechanisms as a major contributor to the effects observed and were supported by findings with the insoluble fibre cellulose and bile acid sequesterant cholestyramine. These findings offer insights into the impacts of GG on lipid digestion, with implications for the development of functional foods.

Graphical abstract

http://ift.tt/2ieLClM

The ATA wishes you a Happy Holiday Season

Season's Greetings to all our Friends of the ATA

The post The ATA wishes you a Happy Holiday Season appeared first on American Thyroid Association.

http://ift.tt/2hdlCp8

Oxalosis with oral manifestations in a patient with chronic renal failure

Abstract

Oxalosis resulting from hyperoxaluria caused by chronic renal failure can be speculated in rare cases among patients with multiple alveolar bone resorption and tooth root resorption events in the oral cavity.

http://ift.tt/2ieGsWV

A woman by Breu Jörg the Elder, Augsburg ca. 1515 Detroit Institute of Art

http://ift.tt/2i3aRIg

A potentiometric non-enzymatic glucose sensor using a molecularly imprinted layer bonded on a conducting polymer

Publication date: 15 May 2017
Source:Biosensors and Bioelectronics, Volume 91
Author(s): Dong-Min Kim, Jong-Min Moon, Won-Chul Lee, Jang-Hee Yoon, Cheol Soo Choi, Yoon-Bo Shim
A non-enzymatic potentiometric glucose sensor for the determination of glucose in the micomolar level in saliva was developed based on a molecularly imprinted polymer (MIP) binding on a conducting polymer layer. A MIP containing acrylamide, and aminophenyl boronic acid, as a host molecule to glucose, was immobilized on benzoic acid-functionalized poly(terthiophene) (pTBA) by the amide bond formation onto a gold nanoparticles deposited-screen printed carbon electrode (pTBA/AuNPs/SPCE). Aromatic boronic acid was incorporated into the MIP layer to stably capture glucose and create a potentiometric signal through the changed pKa value of polymer film by the formation of boronate anion-glucose complex with generation of H⁺ ions by the cis-diol reaction. Reversible binding and extraction of glucose on the sensor surface was observed using a quartz crystal microbalance. Each layer of the sensor probe was characterized by cyclic voltammetry, electrochemical impedance spectroscopy, X-ray photoelectron spectroscopy, and atomic force microscopy. The potentiometric response at the optimized conditions exhibited a wide linear dynamic range of 3.2×10⁻⁷ to 1.0×10⁻³M, with a detection limit of 1.9 (±0.15)×10⁻⁷M. The sensor probe revealed an excellent selectivity and sensitivity for glucose compared to other saccharides. In addition, the reliability of the proposed glucose sensor was evaluated in physiological fluid samples of saliva and finger prick blood.



http://ift.tt/2i498m0

Genetically engineered and self-assembled oncolytic protein nanoparticles for targeted cancer therapy

Publication date: March 2017
Source:Biomaterials, Volume 120
Author(s): Joong-jae Lee, Jung Ae Kang, Yiseul Ryu, Sang-Soo Han, You Ree Nam, Jong Kook Rho, Dae Seong Choi, Sun-Woong Kang, Dong-Eun Lee, Hak-Sung Kim
The integration of a targeted delivery with a tumour-selective agent has been considered an ideal platform for achieving high therapeutic efficacy and negligible side effects in cancer therapy. Here, we present engineered protein nanoparticles comprising a tumour-selective oncolytic protein and a targeting moiety as a new format for the targeted cancer therapy. Apoptin from chicken anaemia virus (CAV) was used as a tumour-selective apoptotic protein. An EGFR-specific repebody, which is composed of LRR (Leucine-rich repeat) modules, was employed to play a dual role as a tumour-targeting moiety and a fusion partner for producing apoptin nanoparticles in E. coli, respectively. The repebody was genetically fused to apoptin, and the resulting fusion protein was shown to self-assemble into supramolecular repebody-apoptin nanoparticles with high homogeneity and stability as a soluble form when expressed in E. coli. The repebody-apoptin nanoparticles showed a remarkable anti-tumour activity with negligible side effects in xenograft mice through a cooperative action of the two protein components with distinct functional roles. The repebody-apoptin nanoparticles can be developed as a systemic injectable and tumour-selective therapeutic protein for targeted cancer treatment.

Graphical abstract

http://ift.tt/2ibGn6v

Bioactive polysaccharide-based pH-sensitive polymers for cytoplasmic delivery of antigen and activation of antigen-specific immunity

Publication date: March 2017
Source:Biomaterials, Volume 120
Author(s): Eiji Yuba, Ayaka Yamaguchi, Yuta Yoshizaki, Atsushi Harada, Kenji Kono
For establishment of cancer immunotherapy, antigen carriers are needed which have functions not only to deliver antigen into cytosol of dendritic cells (DCs), which induces antigen-specific cellular immune responses, but also to activate DCs. We previously reported cytoplasmic delivery of antigen using liposomes modified with pH-sensitive polymers such as carboxylated poly(glycidol)s or dextran. Modification using these polymers provides stable liposomes with pH-sensitive fusogenic/membrane-disruptive ability. For this study, bioactive polysaccharide-based pH-sensitive polymers were constructed to achieve not only cytoplasmic delivery of antigen but also activation of DCs. Curdlan and mannan were used as bioactive polysaccharides because they are known to activate DCs via their respective interactions with Dectin-1 and Dectin-2. Carboxylated curdlan and mannan promoted Th1 cytokine production from DCs, indicating the activation of DCs by these polysaccharide derivatives. These polymer-modified liposomes released their contents at weakly acidic pH and delivered model antigenic proteins into cytosol of DCs. Subcutaneous administration of curdlan derivative-modified or mannan derivative-modified liposomes induced strong antigen-specific immune responses and stronger antitumor effects than those of liposomes modified with dextran derivative. Therefore, bioactive polysaccharide-modified liposomes that achieve both cytoplasmic delivery of antigen and activation of DCs are promising for cancer immunotherapy.



http://ift.tt/2isvfl6

A single fluorescent probe enables clearly discriminating and simultaneously imaging liquid-ordered and liquid-disordered microdomains in plasma membrane of living cells

Publication date: March 2017
Source:Biomaterials, Volume 120
Author(s): Minggang Tian, Yong Liu, Yuming Sun, Ruoyao Zhang, Ruiqing Feng, Ge Zhang, Lifang Guo, Xuechen Li, Xiaoqiang Yu, Jing Zhi Sun, Xiuquan He
Liquid-ordered (Lo) and liquid-disordered (Ld) microdomains in plasma membrane play different yet essential roles in various bioactivities. However, discrimination of the two microdomains in living cells is difficult, due to the similarity in their constituents and structures. Up to now, polarity sensitive probes are the only tool for imaging the two microdomains, but their small difference between emission spectra in the two microdomains (less than 50 nm) limited their application in living cells. In this work, we first presented an aggregation/monomer type of fluorescent probe (2,7-9E-BHVC12) with much larger separation in emission wavelength (up to 100 nm), for dual-color visualizing the two membrane microdomains in living cells. The probe can form red-emissive aggregates and yellow-emissive monomers when induced by Lo and Ld microdomains, respectively, and thus enables clear visualization of the two membrane microdomains in living cells with dual colors, and thus high-fidelity images of substructures of plasma membrane have been obtained. According to the images of three kinds of normal cells and three kinds of cancer cells stained with 2,7-9E-BHVC12, significant difference in plasma membrane microstructure of cancer cells was found. In terms of 2,7-9E-BHVC12, normal cells were mainly consisted of either Lo or Ld microdomains all over their membranes, while cancer cells all clearly display coexistence of Lo and Ld membrane microdomains. Therefore, 2,7-9E-BHVC12 can serve as a powerful tool for studies of membrane microdomains, and the different results of normal and cancer cells would also deepen our understanding in cancer science.



http://ift.tt/2hVflmh

Transient medial prefrontal perturbation reduces false memory formation

Publication date: Available online 24 December 2016
Source:Cortex
Author(s): Ruud M.W.J. Berkers, Marieke van der Linden, Rafael F. de Almeida, Nils C.J. Müller, Leonore Bovy, Martin Dresler, Richard G.M. Morris, Guillén Fernández
Knowledge extracted across previous experiences, or schemas, benefit encoding and retention of congruent information. However, they can also reduce specificity and augment memory for semantically related, but false information. A demonstration of the latter is given by the Deese-Roediger-McDermott (DRM) paradigm, where the studying of words that fit a common semantic schema are found to induce false memories for words that are congruent with the given schema, but were not studied. The medial prefrontal cortex (mPFC) has been ascribed the function of leveraging prior knowledge to influence encoding and retrieval, based on imaging and patient studies. Here, we used transcranial magnetic stimulation to transiently perturb ongoing mPFC processing immediately before participants performed the DRM-task. We observed the predicted reduction in false recall of critical lures after mPFC perturbation, compared to two control groups, whereas veridical recall and recognition memory performance remained similar across groups. These data provide initial causal evidence for a role of the mPFC in biasing the assimilation of new memories and their consolidation as a function of prior knowledge.



http://ift.tt/2i6nW5K

Influence of the Body Schema on Mirror-Touch Synesthesia

Publication date: Available online 24 December 2016
Source:Cortex
Author(s): Jared Medina, Carrie DePasquale
Individuals with mirror-touch synesthesia report feeling touch on their own body when seeing someone else being touched. We examined how the body schema – an on-line representation of body position in space – is involved in mapping touch from a viewed body to one's own body. We showed 45 mirror-touch synesthetes videos of a hand being touched, varying the location of the viewed touch by hand (left, right), skin surface (palmar, dorsal) and finger (index, ring). Participant hand posture was either congruent or incongruent with the posture of the viewed hand. After seeing the video, participants were asked to report whether they felt touch on their own body and, if so, the intensity and location of their percepts. We found that participants reported more frequent and more veridical (i.e. felt at the same somatotopic location as the viewed touch) mirror-touch percepts on posturally congruent versus posturally incongruent trials. Furthermore, participant response patterns varied as a function of postural congruence. Some participants consistently felt sensations on the hand surface that was stimulated in the video – even if their hands were in the opposite posture. Other participants' responses were modulated based on their own hand position, such that percepts were more likely to be felt on the upright, plausible hand surface in the posturally incongruent condition. These results provide evidence that mapping viewed touch to one's own body involves an on-line representation of body position in space.



http://ift.tt/2ieIExV

Sex and APOE: A memory advantage in male APOE ε4 carriers in midlife

Publication date: Available online 24 December 2016
Source:Cortex
Author(s): Nahid Zokaei, Kathrin Giehl, Annie Sillence, Matt J. Neville, Fredrik Karpe, Anna C. Nobre, Masud Husain
Short-term memory in middle-aged individuals with different APOE alleles was examined using a recently developed task which is sensitive to medial temporal lobe damage. Individuals (age-range: 40-51 years) with ε3/ε3, ε3/ε4 and ε4/ε4 APOE genotypes (N=60) performed a delayed estimation task with a sensitive continuous measure of report. The paradigm allowed us to measure memory for items and their locations, as well as maintenance of identity-location feature binding in memory. There was a significant gene-dosage dependent effect of the ε4 allele on performance: memory decay or forgetting was slower in ε4 carriers, as measured by localization error and after controlling for misbinding errors. Furthermore ε4 carriers made less misbinding errors. These findings were specific to male carriers only. Male ε4 carriers are at a behavioral advantage in midlife on a sensitive task of short-term memory. These findings would be consistent with an antagonistic pleiotropy hypothesis, highlighting the interaction of gender on the influence of APOE in cognition.



http://ift.tt/2i6hV9t

Formation of disulfonated poly(arylene ether sulfone) thin film desalination membranes plasticized with poly(ethylene glycol) by solvent-free melt extrusion

Publication date: 27 January 2017
Source:Polymer, Volume 109
Author(s): Hee Jeung Oh, Jaesung Park, Sebnem Inceoglu, Irune Villaluenga, Jacob L. Thelen, Xi Jiang, James E. McGrath, Donald R. Paul
In this study, we discuss a new membrane formation route for preparing sulfonated polysulfone desalination membranes by solvent-free melt processing. Single-layer membranes composed of a 20 mol% disulfonated poly(arylene ether sulfone) random copolymer (BPS-20K) and poly(ethylene glycol) (PEG) plasticizers were successfully prepared by using melt extrusion. The chemical integrity of the components in the BPS-20K/PEG membranes was maintained after the extrusion process, as confirmed by ¹H NMR and FT-IR analysis. Although some of the films appeared opaque after extrusion, this was found to be due to surface roughness. Other factors that might lead to film opacity, such as phase separation, crystallization, or micro-voids, were not found.

Graphical abstract

http://ift.tt/2hjJrih

Synthesis of heat-resistant benzoxazine-based polyfluorene and its reversible temperature-sensitive fluorescence

Publication date: 27 January 2017
Source:Polymer, Volume 109
Author(s): Weizhi Li, Xiangai Yuan, Jin Huang, Bang'an Peng, Feng Zhou, Jing Ma, Xudong Jia
A novel benzoxazine-containing temperature T-sensitive fluorescent polyfluorenes (BluePF-BZ) had been prepared. A benzoxazine monomer (BHPF-paa) was firstly synthesized with 9,9-Bis(4-hydroxyphenyl)fluorene, propargylamine and paraformaldehyde through Mannich condensation reaction. The as-prepared BHPF-paa was then incorporated into the preparation of polyfluorenes, and the main-chain BluePF-BZ could finally be obtained. The structures of the obtained monomer and polyfluorenes were characterized by ¹H NMR and FTIR. The BluePF-BZ was finally incorporated into epoxy resin (E44 + D230) to fabricate the T-sensitive material. The thermal stability, optical stability, and T-sensitive fluorescent properties of BluePF-BZ/E44 + D230 were investigated. The BluePF-BZ/E44 + D230 system showed high spectral thermal stability and reversible T-sensitive fluorescent response in relative high temperature (>433 K). To the best of our knowledge, this is the first report about the T-sensitive fluorescent property of PF. Its mechanism of T-sensitive fluorescent property was also studied by comparative experiment and molecular simulation.

Graphical abstract

http://ift.tt/2hjJvP9

A new class of non-isocyanate urethane methacrylates for the urethane latexes

Publication date: 27 January 2017
Source:Polymer, Volume 109
Author(s): Lei Meng, Xiaojiang Wang, Martin Ocepek, Mark D. Soucek
A series of new urethane methacrylate (UMA) monomers were synthesized with the reaction of ethylene carbonate and aliphatic amines, followed by the reaction with methacrylic anhydride. The monomers were characterized by ¹H, ¹³C nuclear magnetic resonance (NMR), mass (MS), and Fourier transform infrared (FTIR) spectroscopies. Urethane latexes were prepared by monomer-starved semibatch polymerization of the new urethane methacrylates with methyl methacrylate (MMA) and butyl acrylate (BA). A uniform morphology and a unimodal particle distribution were observed by a combination of dynamic light scattering (DLS), ultrasound acoustic attenuation spectroscopy (UAAS), and transmission electron microscopy (TEM). The thermal stability, minimum film formation temperature (MFFT) and thermo-mechanical properties of the urethane latexes were also studied. The inclusion of urethane monomers appeared to have lowered the MFFT via a water plasticization effect, while enhancing the Tg of the final film properties.

Graphical abstract

http://ift.tt/2hjPCmJ

Significant enhancement of elasticity in alginate-clay nanocomposite hydrogels with PEO-PPO-PEO copolymers

Publication date: 27 January 2017
Source:Polymer, Volume 109
Author(s): Wendy L. Hom, Surita R. Bhatia
The mechanical properties of a new type of nanocomposite gel, consisting of varying concentrations of the biopolymer alginate and the synthetic clay Laponite^®, together with the temperature-sensitive copolymer poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO, trade name Pluronic^® F127), are reported. These "ALP" gels (alginate-Laponite^®-Pluronic^®) were prepared and studied using rheology. Gels with multiple networks and gelation mechanisms have been explored as one strategy to strengthen and stiffen conventional hydrogels, which usually consist of a single polymer network. This work shows that the ALP gels exhibit significantly higher storage and loss modulus (G′, G″) values than gels composed of only alginate and Laponite^®. Moreover, the interaction between the components appears to be synergistic; that is, the resulting multicomponent hydrogels are much more elastic than the additive effects of individual components. For example, the G′ of one series of the nanocomposite gels containing F127 Pluronic^® experiences two orders of magnitude enhancement compared to its respective control containing only alginate and Laponite^®. Furthermore, the ALP gels show a 20-40x enhancement in storage modulus, with values as high as 10,000–20,000 Pa, over the 30–55 °C temperature range. The large degree of enhancement in the storage modulus of the ALP gels with addition of Pluronic^® is quite remarkable, compared to alginate-Laponite^® gels on their own at comparable concentrations and temperatures, which form relatively weak gels. These results provide a simple strategy for significantly increasing the mechanical properties of polymer hydrogels used in biomaterials applications.

Graphical abstract

http://ift.tt/2hjJr1L

Impact of degree of sulfonation on microstructure, thermal, thermomechanical and physicochemical properties of sulfonated poly ether ether ketone

Publication date: 27 January 2017
Source:Polymer, Volume 109
Author(s): Soma Banerjee, Kamal K. Kar
Effect of degree of sulfonation on dynamic mechanical properties, dehydration rate, crystallinity, thermal stability and other fuel cell properties (e.g. proton conductivity, ion exchange capacity, water uptake capacity, etc.) of SPEEK membrane are studied and correlated with microstructure. With increasing degree of sulfonation (DS), α-relaxation peak shifts from 135 to 166 °C, while β-relaxation changes from 76 to 37 °C. This peak attribution indicates a plasticizing effect of SO3H group within the crystalline region. Thermal stability of SPEEK decreases while peak degradation temperature for desulfonation and glass transition temperature increase from 320-340 and 191–210 °C, respectively with increasing DS from ∼72 to ∼128%. Likewise, small angle X-ray scattering peak at scattering vector of 0.2 Å⁻¹ shifts to 0.28 Å⁻¹ with an associated increase in intensity due to the evolution of microstructure. Increase in number of scattering centers with progressive sulfonation leads to ionic aggregation, which is the main responsible factor for such evolution. Ionic aggregation is further confirmed by the occurrence of two closely spaced melting peaks in the range of 322–328 and 361–365 °C in differential scanning calorimetry analysis. Dehydration rate gradually increases with increasing DS. Ion exchange capacity, proton conductivity, water uptake and dehydration rate increase from ∼0.49 to ∼2.43 mmol g⁻¹, ∼1.07 × 10⁻⁴ to ∼2.9 × 10⁻² Scm⁻¹, ∼20.36 to ∼135.3% and ∼0.296 to ∼0.51 sec⁻¹, respectively with increase in DS from ∼72 to ∼128%. Microstructure become more homogeneous (less phase separated) at DS of ∼128% resulting in continuous ionic channels for proton conduction.

Graphical abstract

http://ift.tt/2hjI3wj

Warthin tumor within the superficial lobe of the parotid gland: a suggested criterion for diagnosis

Abstract

The location of Warthin tumor (WT) in the parotid gland impacts the surgical approach and may be indicative of the elusive origin of this intriguing entity. Location in the deep versus superficial lobe of the gland is not directly addressed when defining WT characteristics. Our observation, of rare occurrence of deep lobe WT, if at all, led to the current investigation. The study design is cohort study. This is a retrospective chart review of all patients undergoing parotidectomy for WT in two tertiary academic referral centers: the Sheba Medical Center (SMC), Israel, and the Christiana Care (CC), Newark, Delaware, USA. 122 consecutive adult patients underwent parotidectomy for WT (72 from SMC and 50 from CC). Seventy percent were males, with a mean age of 60.6 years. Bilateral WT or multi-centric WT were found in 9.8 and 17.2% of the cases, respectively. In one case, the tumor was described as originating in the deep lobe. In all other cases, the tumor originated and was limited to the superficial lobe. 99.2% of WT originated in the superficial lobe, corresponding with the few reports directly addressing its location in the gland. The reason for the tumor to be limited almost uniformly to the superficial lobe is unknown, and could be related to the etiopathogenesis of this elusive entity. We suggest adding tumor location within the superficial lobe to the common characteristics of WT (male, smoking, and lower pole) that serve as "common criterion" while evaluating a parotid lesion.

http://ift.tt/2irQraD

Warthin tumor within the superficial lobe of the parotid gland: a suggested criterion for diagnosis

Abstract

The location of Warthin tumor (WT) in the parotid gland impacts the surgical approach and may be indicative of the elusive origin of this intriguing entity. Location in the deep versus superficial lobe of the gland is not directly addressed when defining WT characteristics. Our observation, of rare occurrence of deep lobe WT, if at all, led to the current investigation. The study design is cohort study. This is a retrospective chart review of all patients undergoing parotidectomy for WT in two tertiary academic referral centers: the Sheba Medical Center (SMC), Israel, and the Christiana Care (CC), Newark, Delaware, USA. 122 consecutive adult patients underwent parotidectomy for WT (72 from SMC and 50 from CC). Seventy percent were males, with a mean age of 60.6 years. Bilateral WT or multi-centric WT were found in 9.8 and 17.2% of the cases, respectively. In one case, the tumor was described as originating in the deep lobe. In all other cases, the tumor originated and was limited to the superficial lobe. 99.2% of WT originated in the superficial lobe, corresponding with the few reports directly addressing its location in the gland. The reason for the tumor to be limited almost uniformly to the superficial lobe is unknown, and could be related to the etiopathogenesis of this elusive entity. We suggest adding tumor location within the superficial lobe to the common characteristics of WT (male, smoking, and lower pole) that serve as "common criterion" while evaluating a parotid lesion.

http://ift.tt/2irQraD

The effect of motor control training on kinetics variables of patients with non-specific low back pain and movement control impairment: prospective observational study

Publication date: Available online 24 December 2016
Source:Journal of Bodywork and Movement Therapies
Author(s): Vahid Mohammadi, Amir Letafatkar, Haydar Sadeghi, AmirAli Jafarnezhadgero, Roger Hilfiker
IntroductionThe purpose of this study was to determine the effects of motor control training on pain, disability and motor control indices in patients with nonspecific low back pain (NSLBP) and movement control impairment (MCI) and also to evaluate the correlation between the changes in disability and the motor control indices.MethodsThirty people with NSLBP and MCI based on a clinical examination were following either motor control training or normal activity over 8 weeks.ResultSignificant differences between pre and post training in the experimental group were found in pain, disability and motor control indices. There were significant correlations between disability index with vertical ground reaction force (r = 0.43) and center of pressure (anterior-posterior) (r = 0.44) values.ConclusionThe results of this study showed that motor control indices are responsive measures to capture change during motor control training directed at retraining neuromuscular control, reducing pain and disability.



http://ift.tt/2is5MIg

Nanocrystals embedded in chitosan-based respirable swellable microparticles as dry powder for sustained pulmonary drug delivery

Publication date: 1 March 2017
Source:European Journal of Pharmaceutical Sciences, Volume 99
Author(s): Rui Ni, Jing Zhao, Qiaoyu Liu, Zhenglin Liang, Uwe Muenster, Shirui Mao
In this study, nanocrystals embedded in microparticles were designed to achieve sustained pulmonary drug delivery of hydrophobic drugs. Chitosan based microparticles were engineered to allow sustained drug release via swelling and mucoadhesive properties of the polymer. Taking cinaciguat as a hydrophobic model drug, drug nanocrystals were prepared by high pressure homogenization and then encapsulated in chitosan microparticles via spray drying. Through various in vitro characterizations, it was shown that drug loaded microparticles had a high drug loading with promising aerosolization characteristics (mean volume diameter (Dv50) 3–4μm, experimental mass mean aerodynamic diameter (MMADe) 4–4.5μm, fine particle fraction (FPF%) 40–45%, emitted dose (ED%) 94–95%). The microparticles showed high swelling capacity within 5min, with various sustained drug release rates depending on chitosan concentration and molecular weight. Furthermore, aerosolization performances under various inhalation conditions were investigated. It was found that both inspiratory flow rate and volume had an influence on the aerosolization of developed microparticles, indicating actual inhalation efficiency might be compromised under disease conditions. Taken together, in vitro data indicate that chitosan based swellable microparticles could potentially be useful as nanocrystal carrier to achieve sustained pulmonary delivery. To complete the feasibility assessment of this formulation principle, future in vivo safety and efficacy studies are needed.

Graphical abstract

http://ift.tt/2hd1OSS

Pharmacology and toxicology of the novel investigational agent Cantrixil (TRX-E-002-1)

Abstract

Purpose

Recurrent, chemo-resistant ovarian cancer is thought to be due to a subgroup of slow-growing, drug-resistant cancer cells with stem-like properties and a high capacity for tumour repair. Cantrixil targets this sub-population of cells and is being developed as an intraperitoneal therapy to be used as first-line therapy in combination with carboplatin for epithelial ovarian cancer. The studies presented here justify further development.

Methods

A GLP dog CV study using a 4 × 4 Latin Square Crossover study was conducted using telemetric ECG recordings from dogs post IP administration to assess for cardiac abnormalities. Mutagenic potential was assessed using the bacterial reverse mutation assay. Clastogenicity was assessed by determining micronuclei formation in the bone marrow of SPF Arc(S) Swiss mice dosed at clinical concentrations. TRX-E-002-1 toxicology was evaluated in GLP-compliant MTD and 28-day repeat-dose studies in rats and dogs.

Results

In vitro TRX-E-002-1 has potent cytotoxic activity against human cancer cells including CD44+/MyD88+ ovarian cancer stem cells. TRX-E-002-1 increased phosphorylated c-Jun levels in these cancer cells resulting in caspase-mediated apoptosis. In vivo, Cantrixil was active in a model of disseminated ovarian cancer as a monotherapy and in combination with Cisplatin. Cantrixil was active as maintenance therapy in a model of drug-resistant, recurrent ovarian cancer and in an orthotopic model of pancreatic cancer.

Conclusions

In animals, this clinical formulation and route of administration of Cantrixil demonstrated acceptable activity, safety pharmacology, genotoxicity and toxicology profile and constituted a successful Investigational New Drug application to the US Food and Drug Administration.

http://ift.tt/2hd3hZr

The impact of postnatal leuprolide acetate treatment on reproductive characteristics in a rodent model of polycystic ovary syndrome

Publication date: 15 February 2017
Source:Molecular and Cellular Endocrinology, Volume 442
Author(s): Lady Katerine Serrano Mujica, Kalyne Bertolin, Alessandra Bridi, Werner Giehl Glanzner, Vitor Braga Rissi, Flávia de los Santos de Camargo, Renato Zanella, Osmar Damian Prestes, Rafael Noal Moresco, Alfredo Quites Antoniazzi, Paulo Bayard Dias Gonçalves, Melissa Orlandin Premaor, Fabio Vasconcellos Comim
In this study, a GnRH agonist, leuprolide acetate (LA), was given as a single depot injection before 48 h of life to Wistar female rats allotted to prenatal (E16-18) and postnatal androgenization (day 5 of life) by the use of testosterone propionate, looking for reproductive endpoints. Remarkably, a single injection of LA increased the estrus cycles in the postnatal group (PostN) from 0% to 25% of the estrus cycles in the postnatal LA treated group (PostN L). LA also reduced the serum testosterone levels and cysts and atretic follicles in PostN L in contrast with rats (>100 days) from the PostN group (p = 0.04). Prenatally androgenized rats (PreN) exhibited significant modifications in the hypothalamic genes, such as Gnrh. To the best of our knowledge, this is the first study to show that blockage of the GnRH axis with leuprolide acetate depot prevented the development of typical features (anovulation, cysts, atretic follicles) in a postnatal testosterone propionate rat model of PCOS.



http://ift.tt/2iegO4A

Proinsulin C-peptide modulates the expression of ERK1/2, type I collagen and RANKL in human osteoblast-like cells (Saos-2)

Publication date: 15 February 2017
Source:Molecular and Cellular Endocrinology, Volume 442
Author(s): Cristina Russo, Veronica Lazzaro, Carmine Gazzaruso, Samantha Maurotti, Yvelise Ferro, Piero Pingitore, Francesca Fumo, Adriana Coppola, Pietro Gallotti, Valentina Zambianchi, Mariangela Fodaro, Emanuela Galliera, Monica Gioia Marazzi, Massimiliano Marco Corsi Romanelli, Sandro Giannini, Stefano Romeo, Arturo Pujia, Tiziana Montalcini
A lower bone mass accompanied by a higher bone fragility with increased risk of fracture are observed in individuals with type 1 diabetes mellitus. Low C-peptide levels are associated with low lumbar mineral density in postmenopausal woman. In this work, we investigated the role of C-peptide on the osteoblast cell biology in vitro. We examined intracellular pathways and we found that C peptide activates ERK1/2 in human osteoblast-like cells (Saos-2). We also observed that proinsulin C-peptide prevents a reduction of type I collagen expression and decreases, in combination with insulin, receptor activator of nuclear factor-κB (RANKL) levels. In this work we show for the first time that Cpeptide activates a specific intracellular pathway in osteoblasts and it modulates the expression of protein involved in bone remodeling. Our results suggest that both C-peptide may have a role in bone metabolism. Further studies are needing to fully clarify its role.



http://ift.tt/2i5XMjy