Κυριακή 4 Δεκεμβρίου 2016
Non-heme dioxygenases in tumor hypoxia: they’re all bound with the same fate
Publication date: Available online 5 December 2016
Source:DNA Repair
Author(s): Roy Anindya
Tumor tissues are known to harbor hypoxic areas. The hypoxic microenvironment promotes angiogenesis. Hypoxic tumor cells also manifest genome instability. DNA damage repair pathways, such as double-strand break repair, mismatch repair and base excision repair are known to be altered during hypoxia. This review is focused on the non-heme Fe(II) and 2-oxoglutarate-dependent dioxygenases which are involved in repair of DNA alkylation adducts. Activities of these DNA repair enzymes are completely oxygen-dependent and little information is available about inhibition of these enzymes during hypoxia. While impairment of function of non-heme dioxygenase during tumor hypoxia has been implicated in different studies, the possible outcomes with respect to mutagenesis and genomic instability are explored here.
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Burden of herpes zoster and postherpetic neuralgia in Japanese adults 60 years of age or older: Results from an observational, prospective, physician practice-based cohort study
Abstract
Approximately one in three persons will develop herpes zoster during their lifetime, and it can lead to serious complications such as postherpetic neuralgia. However, evidence on burden of herpes zoster and postherpetic neuralgia in Japan is limited. This prospective, observational, multicenter, physician practice-based cohort study was conducted in Kushiro, Hokkaido, Japan (Clinicaltrials.gov identifier NCT01873365) to assess the incidence and hospitalization rates of herpes zoster, and the proportion, clinical burden and risk factors for postherpetic neuralgia in adults aged 60 years or more. Within the study area, 800 subjects developed herpes zoster and 412 were eligible for the study. Herpes zoster incidence was 10.2/1000 person-years and higher among women and older subjects. Subjects with herpes zoster required on average 5.7 outpatient consultations. Herpes zoster-associated hospitalization rate was 3.4% (27/800). The proportion of postherpetic neuralgia and other complications was 9.2% (38/412) and 26.5% (109/412), respectively. Statistically significant association with the development of postherpetic neuralgia was male sex (odds ratio [OR], 2.51; 95% confidence interval [CI], 1.17–5.38), age of 70–74 years (OR, 3.51; 95% CI, 1.09–11.3), immunosuppressive therapy (OR, 6.44; 95% CI, 1.26–32.9), severe herpes zoster pain at first consultation (OR, 3.08; 95% CI, 1.10–8.62) and rash on upper arms (vs no rash on upper arms; OR, 3.46; 95% CI, 1.10–10.9). Considerable herpes zoster and postherpetic neuralgia burden exists among elderly in Japan, and there may be predictive factors at the first visit which could be indicative of the risk of developing postherpetic neuralgia.
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Effects of rinsing with arginine bicarbonate and urea solutions on initial enamel lesions in situ
Abstract
Objective
The aim of this study was to investigate the effects of rinsing with arginine or urea solution on initial enamel lesions in situ.
Methods
Fourteen subjects wore mandibular removable partial dentures embedded with bovine enamel blocks with artificial enamel lesions were included. The experiment included four 4-week rinsing periods with a 10-day washout period between each rinsing period. In each rinsing period, the subjects rinsed after meal or snack using water, or 2% arginine bicarbonate, or 1% urea, or 0.05% NaF solution, 5 times daily. The mineralization changes of the enamel lesions were assessed using quantitative light-induced fluorescence.
Results
All groups except the water group showed a statistically significant decrease in the fluorescence loss after treatment, compared with their respective baseline. Although both the arginine group and urea group showed more decrease of fluorescence loss than that of the water group, the decrease was not statistically significantly different from that of the water group. The decrease of fluorescence loss of the NaF group was statistically significant than that of the water group, arginine group and urea group.
Conclusion
Rinsing with arginine or urea solution offers limited remineralizing benefit to enamel lesions over a period of 4-week time.
This article is protected by copyright. All rights reserved.
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Dental implant loss in older versus younger patients: a systematic review and meta-analysis of prospective studies
Abstract
The aim of this systematic review was to evaluate implant loss in younger and older patients. An electronic search of four databases (MEDLINE, EMBASE, SCOPUS and the Cochrane Library) was undertaken until May 2016 without time restriction and was supplemented by manual searching. Prospective cohorts were included if they met the following criteria: (1) presence of an exposed group (older subjects) with a minimum age of 60 years; (2) presence of a control group (younger subjects) with a maximum age of 59 years; and (3) outcome data considering implant survival or loss. Meta-analyses were performed to evaluate the impact of ageing on implant failure. Of 4,152 potentially eligible articles, 4 were included in the qualitative analysis and quantitative synthesis. The pooled estimates suggest that the risk of implant loss in older patients is not significantly higher (RR = 0.92; 95% CI 0.43 – 1.96, p = 0.83) when compared to younger subjects. This systematic review suggests that age is not a limiting factor for dental implant therapy.
This article is protected by copyright. All rights reserved.
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A two-photon fluorescent probe for biological Cu (Ⅱ) and PPi detection in aqueous solution and in vivo
Publication date: 15 April 2017
Source:Biosensors and Bioelectronics, Volume 90
Author(s): Mengmeng Guo, Pengyu Dong, Yan Feng, Xinguo Xi, Rong Shao, Xiaohe Tian, Buchang Zhang, Manzhou Zhu, Xiangming Meng
The first two-photon fluorescent probe (PC) for selectively detecting biological Cu (Ⅱ) and pyrophosphate (PPi) has been developed based on 7-substituted coumarin in this study. The probe presented excellent selective two-photon "on-off-on" detection signal for Cu(II) /PPi in aqueous solution. The two-photon detection ensemble (PCCu) can detect PPi released from DNA amplification after the polymerase chain reactions (PCR). The probe showed low cytotoxicity and good biocompatibility, and therefore can be applied for imaging Cu(II)/PPi in living cells under two-photon excitation. Furthermore, the ensemble probe (PCCu) was also used to image PPi in deep living rat tissues (~100µm) and in 5-days old zebrafish.
Graphical abstract
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Sensitive immunoassay-based detection of Vibrio parahaemolyticus using capture and labeling particles in a stationary liquid phase lab-on-a-chip
Source:Biosensors and Bioelectronics, Volume 90
Author(s): Byunghee Park, Suk-Jung Choi
In the present study, a method was developed for detection of Vibrio parahaemolyticus based on a stationary liquid phase lab-on-a-chip (SLP LOC). The present SLP LOC comprises a sample chamber, washing chamber, and detection chamber connected by two channels. The method utilizes two types of particles: capture particles (CPs), which are magnetic nanoparticles functionalized with antibody; and labeling particles (LPs), which are silica nanoparticles functionalized with horseradish peroxidase and antibody. Samples were added to the sample chamber with CPs and LPs, forming a CP-bacteria-LP complex, and the complex was transported to the detection chamber containing chromogenic substrate solution. The method allowed the detection of V. parahaemolyticus in the range of 101–105cfu within 45min. Additionally, contamination of oyster samples with V. parahaemolyticus was detected within 2.5h, including 2h of culturing. The present method has the advantage of being highly rapid and facile, and enabling the detection of bacteria with high sensitivity. Moreover, the LOC and LOC processing device used in this method possess simple structures, making the detection process economical and allowing miniaturization. Therefore, the present SLP LOC detection method is potentially useful for in situ determination of food safety.
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A highly specific ratiometric two-photon fluorescent probe to detect dipeptidyl peptidase IV in plasma and living systems
Source:Biosensors and Bioelectronics, Volume 90
Author(s): Li-Wei Zou, Ping Wang, Xing-Kai Qian, Lei Feng, Yang Yu, Dan-Dan Wang, Qiang Jin, Jie Hou, Zhi-Hong Liu, Guang-Bo Ge, Ling Yang
In this study, a highly specific ratiometric two-photon fluorescent probe GP-BAN was developed and well-characterized to monitor dipeptidyl peptidase IV in plasma and living systems. GP-BAN was designed on the basis of the catalytic properties and substrate preference of DPP-IV, and it could be readily hydrolyzed upon addition of DPP-IV under physiological conditions. Both reaction phenotyping and inhibition assays demonstrated that GP-BAN displayed good reactivity and high selectivity towards DPP-IV over other human serine hydrolases including FAP, DPP-VIII, and DPP-IX. The probe was successfully used to monitor the real activities of DPP-IV in complex biological systems including diluted plasma, while it could be used for high throughput screening of DPP-IV inhibitors by using human plasma or tissue preparations as enzyme sources. As a two-photon fluorescent probe, GP-BAN was also successfully used for two-photon imaging of endogenous DPP-IV in living cells and tissues, and showed high ratiometric imaging resolution and deep-tissue penetration ability. Taken together, a ratiometric two-photon fluorescent probe GP-BAN was developed and well-characterized for highly selective and sensitive detection of DPP-IV in complex biological systems, which could serve as a promising imaging tool to explore the biological functions and physiological roles of this key enzyme in living systems.
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Management of Hot Flashes in Women with Breast Cancer Receiving Ovarian Function Suppression
Source:Cancer Treatment Reviews
Author(s): Roberto A. Leon-Ferre, Neil Majithia, Charles L. Loprinzi
Most breast cancers express estrogen and/or progesterone receptors, allowing the opportunity to use anti-estrogen therapies, which have demonstrated substantial efficacy in both the metastatic and adjuvant settings. Young premenopausal women with early-stage high-risk or with metastatic hormone-receptor positive breast cancer may benefit from ovarian function suppression in addition to anti-estrogen medications. While these endocrine manipulations have successfully improved breast cancer outcomes, they may lead to a significant proportion of women experiencing vasomotor symptoms. While not life-threatening, vasomotor symptoms adversely impact quality of life and can result in early treatment discontinuation. For these reasons, supportive management of this treatment-related toxicity is crucial, and clinicians caring for breast cancer patients and survivors should be familiar with the options available and the data behind them. This manuscript will review the pathophysiology, clinical manifestations, quality of life implications and non-estrogenic management options of vasomotor symptoms for women with breast cancer undergoing estrogen depletion.
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Effects and moderators of exercise on quality of life and physical function in patients with cancer: an individual patient data meta-analysis of 34 RCTs.
Source:Cancer Treatment Reviews
Author(s): Laurien M. Buffart, Joeri Kalter, Maike G. Sweegers, Kerry S. Courneya, Robert U. Newton, Neil K. Aaronson, Paul B. Jacobsen, Anne M. May, Daniel A. Galvão, Mai J. Chinapaw, Karen Steindorf, Melinda L. Irwin, Martijn M.Stuiver, Sandi Hayes, Kathleen A. Griffith, Alejandro Lucia, Ilse Mesters, Ellen van Weert, Hans Knoop, Martine M. Goedendorp, Nanette Mutrie, Amanda J. Daley, Alex McConnachie, Martin Bohus, Lene Thorsen, Karl-Heinz Schulz, Camille E. Short, Erica L. James, Ron C. Plotnikoff, Gill Arbane, Martina E. Schmidt, Karin Potthoff, Marc van Beurden, Hester S. Oldenburg, Gabe S. Sonke, Wim H. van Harten, Rachel Garrod, Kathryn H. Schmitz, Kerri M. Winters-Stone, Miranda J. Velthuis, Dennis R. Taaffe, Willem van Mechelen, Marie-José Kersten, Frans Nollet, J. Wenzel Jennifer, Joachim Wiskemann J, I.M. Verdonck-de Leeuw, J. Brug
This individual patient data meta-analysis aimed to evaluate the effects of exercise on quality of life (QoL) and physical function (PF) in patients with cancer, and to identify moderator effects of demographic (age, sex, marital status, education), clinical (body mass index, cancer type, presence of metastasis), intervention-related (intervention timing, delivery mode and duration, and type of control group), and exercise-related (exercise frequency, intensity, type, time) characteristics.Relevant published and unpublished studies were identified in September 2012 via PubMed, EMBASE, PsycINFO, and CINAHL, reference checking and personal communications. Principle investigators of all 69 eligible trials were requested to share IPD from their study. IPD from 34 randomised controlled trials (n=4,519 patients) that evaluated the effects of exercise compared to a usual care, wait-list or attention control group on QoL and PF in adult patients with cancer were retrieved and pooled. Linear mixed-effect models were used to evaluate the effects of the exercise on post-intervention outcome values (z-score) adjusting for baseline values. Moderator effects were studies by testing interactions.Exercise significantly improved QoL (β=0.15, 95%CI=0.10;0.20) and PF (β=0.18,95%CI=0.13;0.23). The effects were not moderated by demographic, clinical or exercise characteristics. Effects on QoL (βdifference_in_effect=0.13, 95%CI=0.03;0.22) and PF (βdifference_in_effect=0.10, 95%CI=0.01;0.20) were significantly larger for supervised than unsupervised interventions.In conclusion, exercise, and particularly supervised exercise, effectively improves QoL and PF in patients with cancer with different demographic and clinical characteristics during and following treatment. Although effect sizes are small, there is consistent empirical evidence to support implementation of exercise as part of cancer care.
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Pituitary stalk interruption syndrome: From clinical findings to pathogenesis
Abstract
Pituitary stalk interruption syndrome is a rare congenital defect manifesting with varying degrees of pituitary hormone deficiency. The signs and symptoms of PSIS during the neonatal period and infancy are often overlooked and therefore diagnosis is delayed. The typical manifestations of PSIS can be detected by magnetic resonance imaging. Several genes in Wnt, Notch and Shh signaling pathways related to hypothalamic-pituitary development, such as PIT1, PROP1, LHX3/LHX4, PROKR2, OTX2, TGIF and HESX1, have been found to be associated with PSIS. Nevertheless, the etiology in the majority of cases still remains unknown. In this review, we provide an overview of clinical features of PSIS and summarize our current understanding of the underlying pathogenic mechanisms for this rare syndrome. Furthermore, we propose future research directions that may help understand the etiology of PSIS.
This article is protected by copyright. All rights reserved.
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Liposomal Irinotecan in the Treatment of Refractory Pancreatic Cancer
Effective therapies against metastatic pancreatic cancer remain limited, and despite treatment, many will ultimately progress. Previously, few options were available for second line therapy in metastatic pancreatic cancer. Liposomal encapsulated irinotecan, in combination with leucovorin-modulated fluorouracil, was found to significantly increase overall survival in patients who have progressed after gemcitabine- based therapy in a large, international, randomized clinical trial (NAPOLI-1). We reviewed the background of systemic therapy for metastatic pancreatic cancer, examined putative mechanisms for the success of encapsulated drugs, and identified recent patent applications on the use of liposomal irinotecan in pancreatic cancer. The landmark NAPOLI-1 trial established a second-line option for those with metastatic pancreatic cancer refractory to gemcitabine chemotherapy, but effective therapies with long duration of response are still lacking. Alternative techniques targeting key driver genes in pancreatic cancer and novel methods of early detection and targeting drugs are currently being explored. How liposomal irinotecan can be integrated into chemotherapy regimens, including neoadjuvant or first line combinations, are currently being tested in clinical trials and covered by several new patent applications.
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Neonatal airway obstruction in bilateral congenital dacryocystocoele: Case report and review of the literature
Publication date: January 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 92
Author(s): Tary Yin, Graeme van der Meer
Bilateral nasal obstruction due to simultaneous bilateral dacrocystocoeles is a rare and potentially life threatening condition. We present a five day old girl with this condition who presented with respiratory distress without any eye signs or symptoms associated with dacryocystocoeles. She was successfully managed with surgery and the clinical and radiological features of this condition are presented here with a review of the literature.
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Surgical scheduling categorization system (SSCS): A novel classification system to improve coordination and scheduling of operative cases in a tertiary pediatric medical system
Publication date: January 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 92
Author(s): Eric A. Gantwerker, Cassandra Bannos, Michael J. Cunningham, Reza Rahbar
ObjectiveTo describe a surgical categorization system to create a universal nomenclature, delineating patient complexity as a first step toward developing a true risk stratification system.MethodsRetrospective database review of all otolaryngology surgical procedures performed in a tertiary pediatric hospital system over one academic year (July 2012–June 2013). All otolaryngology surgical procedures were reviewed, encompassing 8478 procedures on 5711 patients. The attending otolaryngologist assigned surgical scheduling category (SSCS) at the time of case booking based on an institution specific guidelines. The guidelines are as follow: Category I was assigned to American Society of Anesthesiologists physical status classification (ASA) I/II patients, designating them appropriate for institution's suburban ambulatory surgery centers; Category II was ASA I/II patients with social or transportation issues; Category III was ASA I/II patients who required case coordination with other medical or surgical departments; Category IV was reserved for patients of any ASA class whom the surgeon designated to be of a higher complexity.Results8478 total procedures analyzed with 7198 having complete records. 48% were Category I, 13.6% were Category II, 1.9% were Category III and 36.5% were Category IV. The ASA were 34.7% ASA I, 50% ASA II, 13.39% ASA III, and 1.9% ASA IV. Although the largest proportion of patients were ASA II (50%), 39.6% of all ASA II were Category IV. Category IV was split into 54.2% ASA II and 34% ASA III and shows that peri-operative surgical concerns were not encompassed by the ASA system.ConclusionThis surgical categorization system streamlines surgical scheduling in a tertiary pediatric hospital system, particularly with respect to the designation of cases as ambulatory surgery center or main operating room appropriate. The case mix complexity is also readily apparent, enhancing recognition of the coordination and attention required for the perioperative management of high complexity patients. The SSCS helps convey concerns not addressed by ASA physical status alone.
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Subspecialist training program in pediatric otorhinolaryngology of UEMS ORL-HNS section
Publication date: Available online 5 December 2016
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Tomislav Baudoin
The ORL Section and Board of Otorhinolaryngology-Head and Neck Surgery of the European Union of Medical Specialists (UEMS) developed pediatric ORL subspecialty program. The program was created with support and consultation of the European Society of Pediatric Otorhinolaryngology. It is divided into four sections: Pediatric Otology, Pediatric Rhinology and Facial Plastic Surgery, Pediatric Laryngology and Phoniatrics and Pediatric Head and Neck Surgery. After completion of the program, the trainee is supposed to achieve an advanced level of competency. The aim of the program is to serve as a guideline for training centers, enabling them to meet the European Standard as set out by the European Board of UEMS through competency based assessments.
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Preface – microRNAs in endocrine cancers and metabolism
Source:Best Practice & Research Clinical Endocrinology & Metabolism, Volume 30, Issue 5
Author(s): Jan Krützfeldt
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Keyword Index
Source:Best Practice & Research Clinical Endocrinology & Metabolism, Volume 30, Issue 5
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Dry skin conditions are related to the recovery rate of skin temperature after cold stress rather than to blood flow
Abstract
Background
Cutaneous blood flow plays an important role in the thermoregulation, oxygen supply, and nutritional support necessary to maintain the skin. However, there is little evidence for a link between blood flow and skin physiology. Therefore, we conducted surveys of healthy volunteers to determine the relationship(s) between dry skin properties and cutaneous vascular function.
Methods
Water content of the stratum corneum, transepidermal water loss, and visual dryness score were investigated as dry skin parameters. Cutaneous blood flow in the resting state, the recovery rate (RR) of skin temperature on the hand after a cold-stress test, and the responsiveness of facial skin blood flow to local cooling were examined as indices of cutaneous vascular functions. The relationships between dry skin parameters and cutaneous vascular functions were assessed.
Results
The RR correlated negatively with the visual dryness score of skin on the leg but correlated positively with water content of the stratum corneum on the arm. No significant correlation between the resting state of blood flow and dry skin parameters was observed. In both the face and the body, deterioration in skin dryness from summer to winter was significant in subjects with low RR. The RR correlated well with the responsiveness of facial skin blood flow to local cooling, indicating that the RR affects systemic dry skin conditions.
Conclusions
These results suggest that the RR but not blood flow at the resting state is associated with dry skin conditions and is involved in skin homeostasis during seasonal environmental changes.
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Harnessing cancer cell metabolism for theranostic applications using metabolic glycoengineering of sialic acid in breast cancer as a pioneering example
Source:Biomaterials, Volume 116
Author(s): Haitham A. Badr, Dina M.M. AlSadek, Motawa E. El-Houseini, Christopher T. Saeui, Mohit P. Mathew, Kevin J. Yarema, Hafiz Ahmed
Abnormal cell surface display of sialic acids – a family of unusual 9-carbon sugars - is widely recognized as distinguishing feature of many types of cancer. Sialoglycans, however, typically cannot be identified with sufficiently high reproducibility and sensitivity to serve as clinically accepted biomarkers and similarly, almost all efforts to exploit cancer-specific differences in sialylation signatures for therapy remain in early stage development. In this report we provide an overview of important facets of glycosylation that contribute to cancer in general with a focus on breast cancer as an example of malignant disease characterized by aberrant sialylation. We then describe how cancer cells experience nutrient deprivation during oncogenesis and discuss how the resulting metabolic reprogramming, which endows breast cancer cells with the ability to obtain nutrients during scarcity, constitutes an "Achilles' heel" that we believe can be exploited by metabolic glycoengineering (MGE) strategies to develop new diagnostic methods and therapeutic approaches. In particular, we hypothesize that adaptations made by breast cancer cells that allow them to efficiently scavenge sialic acid during times of nutrient deprivation renders them vulnerable to MGE, which refers to the use of exogenously-supplied, non-natural monosaccharide analogues to modulate targeted aspects of glycosylation in living cells and animals. In specific, once non-natural sialosides are incorporated into the cancer "sialome" they can be exploited as epitopes for immunotherapy or as chemical tags for targeted delivery of imaging or therapeutic agents selectively to tumors.
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Early-Onset Epileptic Encephalopathy in infants with different forms of Congenital Disorders of Glycosylation (CDG)
Source:Brain and Development
Author(s): Agata Fiumara, Rita Barone, Giuliana Del Campo, Pasquale Striano, Jaak Jaeken
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Total corpus callosotomy for epileptic spasms after acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) in a case with tuberous sclerosis complex
Source:Brain and Development
Author(s): Tohru Okanishi, Ayataka Fujimoto, Hirotaka Motoi, Sotaro Kanai, Mitsuyo Nishimura, Tomohiro Yamazoe, Atsushi Takagi, Takamichi Yamamoto, Hideo Enoki
Corpus callosotomy is a palliative therapy for refractory epilepsy, including West syndrome, without a resectable epileptic focus. The surgical outcome of corpus callosotomy is relatively favorable in cryptogenic (non-lesional) West syndrome. Tuberous sclerosis complex (TSC) is a disorder that frequently leads to the development of refractory seizures by multiple cortical tubers. The multiple cortical tubers cause multiple or wide epileptic networks in these cases. Most of West syndrome cases in TSC with multiple tubers need additional resective surgery after corpus callosotomy.We describe a case of TSC in a boy aged 4years and 8months. He had multiple cortical tubers on his brain and developed epileptic spasms. The seizures were controlled with valproate. At the age of 1year and 4months, he presented with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), and had relapsed epileptic spasms one month after the onset of the encephalopathy. The seizures were refractory to multiple antiepileptic drugs. A total corpus callosotomy was performed at the age of 3years and 8months. The patient did not show any seizures after the surgery. During 12months of the follow-up, the patient was free from any seizures. Even in cases of symptomatic WS with multiple lesions, total corpus callosotomy may be a good strategy if the patients have secondary diffuse brain insults.
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A new role for GABAergic transmission in the control of male rat sexual behavior expression
Source:Behavioural Brain Research, Volume 320
Author(s): Gabriela Rodríguez-Manzo, Ana Canseco-Alba
GABAergic transmission in the ventral tegmental area (VTA) exerts a tonic inhibitory influence on mesolimbic dopaminergic neurons' activity. Blockade of VTA GABAA receptors increases dopamine release in the nucleus accumbens (NAcc). Increases in NAcc dopamine levels typically accompany sexual behavior display. Copulation to satiety is characterized by the instatement of a long lasting (72h) sexual behavior inhibition and the mesolimbic system appears to be involved in this phenomenon. GABAergic transmission in the VTA might play a role in the maintenance of this long lasting sexual inhibitory state. To test this hypothesis, in the present work we investigated the effect of GABAA receptor blockade in sexually exhausted males 24h after copulation to satiety, once the sexual inhibitory state is established, and compared it with its effect in sexually experienced rats. Results showed that low doses of systemically administered bicuculline induced sexual behavior expression in sexually exhausted rats, but lacked an effect on copulation of sexually experienced animals. Intra-VTA bilateral infusion of bicuculline did not modify sexual behavior of sexually experienced rats, but induced sexual behavior expression in all the sexually exhausted males. Hence, GABA plays a role in the control of sexual behavior expression at the VTA. The role played by GABAergic transmission in male sexual behavior expression of animals with distinct sexual behavior conditions is discussed.
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Comparative efficacy and acceptability of electroconvulsive therapy versus repetitive transcranial magnetic stimulation for major depression: A systematic review and multiple-treatments meta-analysis
Source:Behavioural Brain Research, Volume 320
Author(s): Jian-jun Chen, Li-bo Zhao, Yi-yun Liu, Song-hua Fan, Peng Xie
BackgroundsThe effects of electroconvulsive therapy (ECT) and bilateral, left prefrontal, and right prefrontal repetitive transcranial magnetic stimulation (rTMS) on major depressive disorder (MDD) have not been adequately addressed by previous studies. Here, a multiple-treatments meta-analysis, which incorporates evidence from direct and indirect comparisons from a network of trials, was performed to assess the efficacy and acceptability of these four treatment modalities on MDD.MethodThe literature was searched for randomized controlled trials (RCTs) on ECT, bilateral rTMS, and unilateral rTMS for treating MDD up to May 2016. The main outcome measures were response and drop-out rates.ResultsData were obtained from 25 studies consisting of 1288 individuals with MDD. ECT was non-significantly more efficacious than B-rTMS, R-rTMS, and L-rTMS. Left prefrontal rTMS was non −significantly less efficacious than all other treatment modalities. In terms of acceptability, R-rTMS was non-significantly better tolerated than ECT, B-rTMS, and L-rTMS. ECT was the most efficacious treatment with the cumulative probabilities of being the most efficacious treatment being: ECT (65%), B-rTMS (25%), R-rTMS (8%), and L-rTMS (2%). R-rTMS was the best-tolerated treatment with the cumulative probabilities of being the best-tolerated treatment being: R-rTMS (52%), B-rTMS (17%), L-rTMS (16%), and ECT (14%). Coherence analysis detected no statistically significant incoherence in any comparisons of direct with indirect evidence for the response rate and drop-out rate.ConclusionsECT was the most efficacious, but least tolerated, treatment, while R-rTMS was the best tolerated treatment for MDD. B-rTMS appears to have the most favorable balance between efficacy and acceptability.
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Prodynorphin and kappa opioid receptor mRNA expression in the brain relates to social status and behavior in male European starlings
Source:Behavioural Brain Research, Volume 320
Author(s): Lauren V. Riters, Melissa A. Cordes, Sharon A. Stevenson
Numerous animal species display behavioral changes in response to changes in social status or territory possession. For example, in male European starlings only males that acquire nesting sites display high rates of sexual and agonistic behavior. Past studies show that mu and delta opioid receptors regulate behaviors associated with social ascension or defeat. Opioids also act at kappa receptors, with dynorphin binding with the highest affinity; however, the role of these opioids in social behavior has not been well studied. We observed flocks of male starlings during the breeding season and ran quantitative real-time polymerase chain reaction (qPCR) to measure expression of kappa opioid receptors (OPRK1) and prodynorphin (PDYN) in brain regions involved in social behavior and motivation (ventral tegmental area [VTA], medial preoptic nucleus [mPOA]) and vocal behavior (Area X). Males with nesting territories displayed more sexual/agonistic behavior than males without nesting territories. They also had lower OPRK1 expression in VTA and mPOA. OPRK1 expression in VTA correlated negatively with sexual/agonistic behaviors, consistent with past studies showing kappa receptors in VTA to inhibit sociosexual behaviors. PDYN in mPOA correlated negatively with a measure of nesting behavior that may also reflect sexual motivation. PDYN in Area X related positively to song. Distinct patterns of OPRK1 and PDYN expression in VTA, mPOA, and Area X related to gonad volume, suggesting that breeding condition may modify (or be modified by) OPRK1 and PDYN expression. Studies are now needed to further characterize the role of OPRK1 and PDYN in status-appropriate social behaviors.
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The chemotherapeutic agent paclitaxel selectively impairs learning while sparing source memory and spatial memory
Source:Behavioural Brain Research, Volume 320
Author(s): Alexandra E. Smith, Richard A. Slivicki, Andrea G. Hohmann, Jonathon D. Crystal
Chemotherapeutic agents are widely used to treat patients with systemic cancer. The efficacy of these therapies is undermined by their adverse side-effect profiles such as cognitive deficits that have a negative impact on the quality of life of cancer survivors. Cognitive side effects occur across a variety of domains, including memory, executive function, and processing speed. Such impairments are exacerbated under cognitive challenges and a subgroup of patients experience long-term impairments. Episodic memory in rats can be examined using a source memory task. In the current study, rats received paclitaxel, a taxane-derived chemotherapeutic agent, and learning and memory functioning was examined using the source memory task. Treatment with paclitaxel did not impair spatial and episodic memory, and paclitaxel treated rats were not more susceptible to cognitive challenges. Under conditions in which memory was not impaired, paclitaxel treatment impaired learning of new rules, documenting a decreased sensitivity to changes in experimental contingencies. These findings provide new information on the nature of cancer chemotherapy-induced cognitive impairments, particularly regarding the incongruent vulnerability of episodic memory and new learning following treatment with paclitaxel.
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Co-distribution of cysteine cathepsins and matrix metalloproteases in human dentin
Source:Archives of Oral Biology, Volume 74
Author(s): Polliana Mendes Candia Scaffa, Lorenzo Breschi, Annalisa Mazzoni, Cristina de Mattos Pimenta Vidal, Rosa Curci, Fabianni Apolonio, Pietro Gobbi, David Pashley, Leo Tjäderhane, Ivarne Luis dos Santos Tersariol, Fábio Dupart Nascimento, Marcela Rocha Carrilho
It has been hypothesized that cysteine cathepsins (CTs) along with matrix metalloproteases (MMPs) may work in conjunction in the proteolysis of mature dentin matrix. The aim of this study was to verify simultaneously the distribution and presence of cathepsins B (CT-B) and K (CT-K) in partially demineralized dentin; and further to evaluate the activity of CTs and MMPs in the same tissue. The distribution of CT-B and CT-K in sound human dentin was assessed by immunohistochemistry. A double-immunolabeling technique was used to identify, at once, the occurrence of those enzymes in dentin. Activities of CTs and MMPs in dentin extracts were evaluated spectrofluorometrically. In addition, in situ gelatinolytic activity of dentin was assayed by zymography. The results revealed the distribution of CT-B and CT-K along the dentin organic matrix and also indicated co-occurrence of MMPs and CTs in that tissue. The enzyme kinetics studies showed proteolytic activity in dentin extracts for both classes of proteases. Furthermore, it was observed that, at least for sound human dentin matrices, the activity of MMPs seems to be predominant over the CTs one.
http://ift.tt/2h3RJbe
Effect of morin-5′-sulfonic acid sodium salt on the expression of apoptosis related proteins caspase 3, Bax and Bcl 2 due to the mercury induced oxidative stress in albino rats
Publication date: Available online 3 December 2016
Source:Biomedicine & Pharmacotherapy
Author(s): Rantham Subramaniam Venkatesan, Abdul Majeeth Mohamed Sadiq
Many environmental contaminants have been reported to disturb the pro-oxidant or antioxidant balance of the cells by inducing oxidative stress. Oxidative stress mediated by the HgCl2 induces DNA, protein and lipid oxidation resulted in necrosis or apoptosis, or both. Currently flavonoids are being emerging topic and reported to have antiviral, anti-inflammatory, anti- tumor and antioxidant activities. Morin is one of the flavonoid protects the cells from oxygen free radical damage and scavenges the free radicals and metals and also heals the injured cells commercially. Morin hydrate is sparingly soluble in water. Hence, the water soluble morin -5′- sulfonic acid sodium salt (NaMSA) was selected and synthesized. Aim of the present study was to analyze the effect of morin-5′-sulfonic acid sodium salt on the expression of apoptosis related proteins caspase 3, Bax and Bcl 2 due to the mercury induced oxidative stress in albino rats.. The experimental rats were exposed to sub lethal concentration of mercuric chloride (1.25mg/kg) and the ameliorating effect of NaMSA was studied by using apoptotic protein markers Bax and caspase-3 and Bcl-2. The obtained results were analyzed using one way analysis of variance by the Duncan's Multiple comparison test to determine the level of significance (p) and p<0.05 was considered as statistically significant. Administration of mercuric chloride (1.25mg/kg) in the experimental rats increased the expression of Bax and caspase-3 and a decreased expression was noted in the Bcl-2 level compared with control bands significantly (p<0.05). On the other hand NaMSA (50mg/kg) and HgCl2 (1.25mg/kg) simultaneous administration did not bring any change in the protein expression of Bax, Caspase-3 and Bcl-2 levels compared with control rats. Hence, the membrane damage was protected, stopped the cell death and apoptosis. This could be due to the morin-5′-sulfonic acid sodium salt effective chelation action on the HgCl2 generated free radicals.
http://ift.tt/2gEtt2u
Histone deacetylases 3 deletion restrains PM2.5-induced mice lung injury by regulating NF-κB and TGF-β/Smad2/3 signaling pathways
Publication date: Available online 3 December 2016
Source:Biomedicine & Pharmacotherapy
Author(s): Li-Zhi Gu, Hong Sun, Jian-Hui Chen
Acute lung injury (ALI) as a serious disease with high mortality has been emphasized as a threat to human health and life. Accumulating studies demonstrated that PM2.5 plays a significant role in metabolic and lung diseases. Histone deacetylases 3 (HDAC3) is an important regulator in control of gene transcription, required in up-regulation of inflammation-related signaling, and has been known as a key hotpot in treating a lot of chronic inflammatory diseases. TGF-β/Smad signaling pathway has been proven to be of significance in fibrosis development. Our results found that PM2.5 induced lung function injury in WT mice with a inflammatory responses through the activation of TGF-β/Smad signaling pathways, resulting in lung injury. Of note, HDAC3-deficient mice after PM2.5 administration further promoted TGF-β/Smad signaling pathways activation. In addition, TLR4, p-NF-κB and p-IκBα indicated that HDAC3 knockout mice have a higher inflammation-related signals expression in lung tissue than WT mice after PM2.5 administration, resulting in pro-inflammatory cytokines releasing. Moreover, in vitro experiment of lung epithelial cells challenged with PM2.5, further indicated that TGF-β/Smad2/3 was involved in fibrosis development, leading to inflammation response. Also, the activation of TLR4/NF-κB could be observed in PM2.5-induced lung epithelial cells, leading to inflammation infiltration. These results indicate a new therapeutic target to protect against lung injury caused by PM2.5.
http://ift.tt/2gqku21
Quercetin attenuates high fructose feeding-induced atherosclerosis by suppressing inflammation and apoptosis via ROS-regulated PI3K/AKT signaling pathway
Publication date: Available online 3 December 2016
Source:Biomedicine & Pharmacotherapy
Author(s): Xue-Li Lu, Cui-Hua Zhao, Xin-Liang Yao, Han Zhang
Quercetin is a dietary flavonoid compound extracted from various plants, such as apple and onions. Previous studies have revealed its anti-inflammatory, anti-cancer, antioxidant and anti-apoptotic activities. This study investigated the ability of quercetin to inhibit high fructose feeding- or LPS-induced atherosclerosis through regulating oxidative stress, apoptosis and inflammation response in vivo and in vitro experiments. 50 and 100mg/kg quercetin were used in our study, showing significant inhibitory role in high fructose-induced atherosclerosis via reducing reactive oxygen species (ROS) levels, Caspase-3 activation, inflammatory cytokines releasing, the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells and collagen contents as well as modulating apoptosis- and inflammation-related proteins expression. We also explored the protective effects of quercetin on atherosclerosis by phosphatidylinositide 3-kinases (PI3K)/Protein kinase B (AKT)-associated Bcl-2/Caspase-3 and nuclear factor kappa B (NF-κB) signal pathways activation, promoting AKT and Bcl-2 expression and reducing Caspase-3 and NF-κB activation. Quercetin reduced the atherosclerotic plaque size in vivo in high fructose feeding-induced mice assessed by oil red O. Also, in vitro experiments, quercetin displayed inhibitory role in LPS-induced ROS production, inflammatory response and apoptosis, which were linked with PI3K/AKT-regulated Caspase-3 and NF-κB activation. In conclusion, our results showed that quercetin inhibited atherosclerotic plaque development in high fructose feeding mice via PI3K/AKT activation regulated by ROS.
http://ift.tt/2gEgz4s
Relative costs of anesthesiologist prepared, hospital pharmacy prepared and outsourced anesthesia drugs
Anesthesia drugs can be prepared by anesthesia providers, hospital pharmacies or outsourcing facilities. The decision whether to outsource all or some anesthesia drugs is challenging since the costs associated with different anesthesia drug preparation methods remain poorly described.
http://ift.tt/2gRbFyX
Proton therapy – Present and future
Publication date: Available online 3 December 2016
Source:Advanced Drug Delivery Reviews
Author(s): Radhe Mohan, David Grosshans
In principle, proton therapy offers a substantial clinical advantage over the conventional photon therapy. This is because of the unique depth-dose characteristics of protons, which can be exploited to achieve significant reductions in normal tissue doses proximal and distal to the target volume. These may, in turn, allow escalation of tumor doses, greater sparing of normal tissues, thus potentially improving local control and survival while at the same time reducing toxicity and improving quality of life.Protons, accelerated to therapeutic energies ranging from 70 to 250MeV, typically with a cyclotron or a synchrotron, are transported to the treatment room where they enter the treatment head mounted on a rotating gantry. The initial thin beams of protons are spread laterally and longitudinally and shaped appropriately to deliver treatments. Spreading and shaping can be achieved by electro-mechanical means to treat the patients with "passively-scattered proton therapy" (PSPT); or using magnetic scanning of thin "beamlets" of protons of a sequence of initial energies. The latter technique can be used to treat patients with optimized intensity modulated proton therapy (IMPT), the most powerful proton modality.Despite the high potential of proton therapy, the clinical evidence supporting the broad use of protons is mixed. It is generally acknowledged that proton therapy is safe, effective and recommended for many types of pediatric cancers, ocular melanomas, chordomas and chondrosarcomas. Although promising results have been and continue to be reported for many other types of cancers, they are based on small studies. Considering the high cost or establishing and operating proton therapy centers, questions have been raised about their cost effectiveness. General consensus is that there is a need to conduct randomized trials and/or collect outcomes data in multi-institutional registries to unequivocally demonstrate the advantage of protons.Treatment planning and plan evaluation of PSPT and IMPT requires special considerations compared to the processes used for photon treatment planning. The differences in techniques arise from the unique physical properties of protons but are also necessary because of the greater vulnerability of protons to uncertainties, especially from inter- and intra-fractional variations in anatomy. These factors must be considered in designing as well as evaluating treatment plans. In addition to anatomy variations, other sources of uncertainty in dose delivered to the patient include the approximations and assumptions of models used for computing dose distributions for planning of treatments. Furthermore, the relative biological effectiveness (RBE) of protons is simplistically assumed to have a constant value of 1.1. In reality, the RBE is variable and a complex function of energy of protons, dose per fraction, tissue and cell type, end point, etc.These uncertainties, approximations and current technological limitations of proton therapy may limit the achievement of the true potential of proton therapy. Ongoing research is aimed at better understanding the consequences of the various uncertainties on proton therapy, and reducing the uncertainties image-guidance, adaptive radiotherapy, further study of biological properties of protons, and the development of novel dose computation and optimization methods. However, residual uncertainties will remain in spite of the best efforts. To increase the resilience of dose distributions in the face of uncertainties and improve our confidence in dose distributions seen on treatment plans, robust optimization techniques are being developed and implemented. We assert that, with such research, proton therapy will be a commonly applied radiotherapy modality for most types of solid cancers in the near future.
Graphical abstract
http://ift.tt/2h6A3Qk
Complement in basic processes of the cell
Source:Molecular Immunology
Author(s): Anaïs Jiménez-Reinoso, Ana V. Marin, José R. Regueiro
The complement system is reemerging in the last few years not only as key element of innate immunity against pathogens, but also as a main regulator of local adaptive responses, affecting dendritic cells as well as T and B lymphocytes. We review data showing that leucocytes are capable of significant autocrine synthesis of complement proteins, and express a large range of complement receptors, which in turn regulate their differentiation and effector functions while cross talking with other innate receptors such as Toll-like receptors. Other unconventional roles of complement proteins are reviewed, including their impact in non-leukocytes and their intracellular cleavage by vesicular proteases, which generate critical cues required for T cell function. Thus, leucocytes are very much aware of complement-derived information, both extracellular and intracellular, to elaborate their responses, offering rich avenues for therapeutic intervention and new hypothesis for conserved major histocompatibility complex complotypes.
http://ift.tt/2gDgga7
Complement in basic processes of the cell
Source:Molecular Immunology
Author(s): Anaïs Jiménez-Reinoso, Ana V. Marin, José R. Regueiro
The complement system is reemerging in the last few years not only as key element of innate immunity against pathogens, but also as a main regulator of local adaptive responses, affecting dendritic cells as well as T and B lymphocytes. We review data showing that leucocytes are capable of significant autocrine synthesis of complement proteins, and express a large range of complement receptors, which in turn regulate their differentiation and effector functions while cross talking with other innate receptors such as Toll-like receptors. Other unconventional roles of complement proteins are reviewed, including their impact in non-leukocytes and their intracellular cleavage by vesicular proteases, which generate critical cues required for T cell function. Thus, leucocytes are very much aware of complement-derived information, both extracellular and intracellular, to elaborate their responses, offering rich avenues for therapeutic intervention and new hypothesis for conserved major histocompatibility complex complotypes.
http://ift.tt/2gDgga7
Distal Endovascular Fenestration INsIde Thoracic Exclusion: The DEFINITE Technique for Complicated Acute Type B Aortic Dissections
Publication date: Available online 3 December 2016
Source:European Journal of Vascular and Endovascular Surgery
Author(s): F. Alomran, J.-M. Alsac
http://ift.tt/2gVcrOe
Editorial Board
Source:Addictive Behaviors, Volume 65
http://ift.tt/2gCMxOz
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