T Cell Response in Patients with Implanted Biological and Mechanical Prosthetic Heart Valves

The study was aimed at assessing T cell subsets of peripheral blood from recipients of long-term functioning (more than 60 months) biological and mechanical heart valve prostheses. The absolute and relative number of CD4 and CD8 T cell subsets was analyzed: naïve (N, CD45RA+CD62L+), central memory (CM, CD45RA−CD62L+), effector memory (EM, CD45RA−CD62L−), and terminally differentiated CD45RA-positive effector memory (TEMRA, CD45RA+CD62L−) in 25 persons with biological and 7 with mechanical prosthesis compared with 48 apparently healthy volunteers. The relative and absolute number of central memory and naïve CD3+CD8+ in patients with biological prosthesis was decreased (). Meanwhile the number of CD45RA+CD62L−CD3+CD8+ and CD3+CD4+ was increased (). Patients with mechanical prosthesis had increased absolute and relative number of CD45RA+CD62L−CD3+CD8+ cells (). Also the relative number of CD3+CD4+ cells was reduced (). We assume that altered composition of T cell subsets points at development of xenograft rejection reaction against both mechanical and biological heart valve prostheses.

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Diode endovascular laser treatment in venous malformations of the upper aerodigestive tract

Diode endovascular laser treatment in venous malformations of the upper aerodigestive tract

via ScienceDirect Publication: Journal of Cranio-Maxillofacial Surgery

Publication date: Available online 15 February 2016
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): François Simon, Nicolas Le Clerc, Didier Salvan, Elisabeth Sauvaget, Benoît Faucon, Michel Borsik, Philippe Herman, Annouk Bisdorff
PurposeVenous malformations of the upper aerodigestive tract can cause pain, dysphagia, obstructive sleep apnea, and rarely bleeding. We studied 980-nm diode endovenous laser therapy.Material and MethodsThis is a 2007–2014 retrospective study in our vascular anomalies center. Data on patients' clinical history, polysomnography, magnetic resonance imaging, and treatment were collected. Patients were contacted for Epworth Sleepiness Scale and Eating Assessment Tool (EAT-10) scores to evaluate sleepiness and dysphagia before and after laser therapy.ResultsWe included 32 patients (mean age 41 years) presenting with obstructive sleep apnea (n = 18) and dysphagia (n = 13). With a mean follow-up of 39 months, average Epworth Sleepiness Scale score fell from 17.3 to 10.4 (p = 0.015), EAT-10 score from 8.2 to 3.5 (p=0.002) and apnea–hypopnea index from 47.5 to 24.7 (p = 0.01). Of the sleep apnea patients, 89% required continuous positive airway pressure before and 50% afterward (p = 0.016).ConclusionsDiode endovascular laser treatment seems to be a safe and effective treatment option in venous malformations of the upper airways.

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Oral diseases in pediatric HIV-infected populations

The global burden of oral diseases in pediatric HIV-infected populations: a workshop report:

Objectives

To achieve a comprehensive understanding about the global burden of oral diseases in HIV-infected children and to identify research needs.

Materials and methods

A literature search was conducted in PubMed (2009–2014) to address five questions: (i) prevalence of oral diseases in HIV-infected compared with uninfected children, (ii) impact of oral diseases on quality of life, (iii) effect of antiretroviral exposure in utero on craniofacial and dental development, (iv) important co-infections and antiretroviral complications, and (v) value of atraumatic restorative treatment.

Results

Studies showed a high prevalence of dental caries in HIV-infected children but the relationship between HIV infection and dental caries remains unclear. Also quality of life needs further investigation supported by better study designs and improvement of the instruments used. Up-to-date evidence suggested long-term harms associated with in utero antiretroviral exposure were minor but would require long-term follow-up through National Registries. The reviews also revealed the wide spectrum of metabolic disease due to antiretroviral therapy and co-infections such as tuberculosis. Finally, atraumatic restorative technique appears to be a simple and safe technique to treat dental caries but outcomes need further evaluation.

Conclusions

The impact of antiretroviral therapy in HIV-infected children has raised novel challenging questions in the field of oral health warranting future research.

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Human papilloma virus and other biologic markers in nasopharyngeal cancer

Clinical implications of human papilloma virus and other biologic markers in nasopharyngeal cancer: Human papilloma virus (HPV) is associated with both the occurrence and prognosis of oropharyngeal cancer. However, few studies have examined the relationship between HPV and nasopharyngeal cancer (NPC). This study investigated the clinical implications of HPV and other molecular markers, including p16, p53, and epidermal growth factor receptor (EGFR), for NPC patients.

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Infraorbital necrotising fasciitis

Infraorbital necrotising fasciitis: importance of rehabilitation in vulnerable patients: A 31-year-old woman presented to the accident and emergency department after a blunt force injury to the right side of her face from an alleged assault. She had mental health problems and a history of substance misuse. There was periorbital swelling, but all investigations were within normal limits. The next day her right eye swelled with pus and she had signs of acute sepsis (Fig. 1). She was diagnosed with necrotising fasciitis by the maxillofacial team, and immediately taken to the operating theatre for debridement.

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Natural position of the head

: review of two-dimensional and three-dimensional methods of recording

via British Journal of Oral and Maxillofacial Surgery

Publication date: Available online 16 February 2016
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): D. Cassi, C. De Biase, I. Tonni, M. Gandolfini, A. Di Blasio, M.G. Piancino
Both the correct position of the patient's head and a standard system for the acquisition of images are essential for objective evaluation of the facial profile and the skull, and for longitudinal superimposition. The natural position of the head was introduced into orthodontics in the late 1950s, and is used as a postural basis for craniocervical and craniofacial morphological analysis. It can also have a role in the planning of the surgical correction of craniomaxillofacial deformities. The relatively recent transition in orthodontics from 2-dimensional to 3-dimensional imaging, and from analogue to digital technology, has renewed attention in finding a versatile method for the establishment of an accurate and reliable head position during the acquisition of serial records. In this review we discuss definition, clinical applications, and procedures to establish the natural head position and their reproducibility. We also consider methods to reproduce and record the position in two and three planes.

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Reaction of glass ionomer cements

Evidence of a complex species controlling the setting reaction of glass ionomer cements

via Dental Materials

Publication date: Available online 15 February 2016
Source:Dental Materials
Author(s): Brett Dickey, Richard Price, Daniel Boyd
ObjectiveTo elucidate the mechanism(s) responsible for the profound impact germanium has on the setting reaction of zinc silicate glass ionomer cements (GICs).MethodsFive <45μm glass powder compositions (0.48-xSiO2, xGeO2, 0.36 ZnO, 0.16 CaO; where x=0.12, 0.24, 0.36, 0.48mol. fraction) were synthesized. Glass degradation was assessed under simulated setting conditions using acetic acid from 0.5 to 60min, monitoring the concentrations of ions released using ICP-OES. Subsequently, GICs were prepared by mixing fresh glass powders with polyacrylic acid (PAA, Mw=12,500g/mol, 50wt% aq. solution) at a 1:0.75 ratio. Cement structure and properties were evaluated using ATR-FTIR and rheology (for 60min), as well as 24h biaxial flexural strength.ResultsReduced Si:Ge ratios yielded faster degrading glasses, yet contrary to expectation, the corresponding ATR-FTIR spectra indicated slower crosslinking within the GIC matrix. Rheology testing found the initial viscosity cement pastes reduced with decreased Si:Ge, and Ge containing cements all set significantly slower than the Si based GIC. Interestingly, biaxial flexural strength remained consistent regardless of setting behavior.SignificanceThis counter-intuitive combination of behaviors is attributed to the presence of a chemical complex species specific to Ge-containing glasses that delays, but does not hinder, the formation of the GIC matrix. These findings embody chemical complex species as a mechanism to decouple glass reactivity from cement setting rate, a mechanism with the potential to enhance the utility of GICs in both dental and orthopaedic applications.

Graphical abstract

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Systemic T Cells and Monocyte Characteristics in Patients with Denture Stomatitis

Systemic T Cells and Monocyte Characteristics in Patients with Denture Stomatitis:

Abstract

Purpose

Chronic inflammatory disorders of the oral cavity, such as periodontitis, were recently linked to systemic immune activation. Since fungal oral infections have not yet been studied in this respect, the aim of our study is to determine whether the local inflammation caused by oral fungal infection of the palatal tissue (denture stomatitis—DS) is associated with the systemic inflammatory response. This question is becoming essential as the population ages.

Materials and Methods

Peripheral blood of DS patients (n = 20) and control patients (n = 24) was assessed with flow cytometry to determine lymphocyte and monocyte profiles. Intracellular cytometric analysis was carried out to establish cytokine production by T cells. DS was diagnosed based on clinical symptoms of DS such as swelling and redness of oral mucosa, confirmed by microbiological swabs for fungal colonization with Candida species. The control group was recruited from denture users without clinical and microbiological signs of oral infections.

Results

Percentages of peripheral lymphocytes, T cells, monocytes, and their subpopulations were similar in both studied groups. The exception was median percentages of CD25+ T cell subsets, which were significantly lower in DS patients than in control subjects. This reduction was observed in both CD4 T cell subset (16.7% and 28.1%; p = 0.0006) and CD8 T cell subset (4.6% and 7.0%; p = 0.007)

Conclusions

While DS and associated local fungal infection do not overtly affect activation of monocytes or lymphocytes, the number of CD 25+ T cells is significantly lower in the DS patients, possibly indicating limited potential for the infection clearance in denture-using aging patients.

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Age-Related Changes in Binaural Interaction at Brainstem Level.

Age-Related Changes in Binaural Interaction at Brainstem Level.: Objectives: Age-related hearing loss hampers the ability to understand speech in adverse listening conditions. This is attributed to a complex interaction of changes in the peripheral and central auditory system. One aspect that may deteriorate across the lifespan is binaural interaction. The present study investigates binaural interaction at the level of the auditory brainstem. It is hypothesized that brainstem binaural interaction deteriorates with advancing age.

Design: Forty-two subjects of various age participated in the study. Auditory brainstem responses (ABRs) were recorded using clicks and 500 Hz tone-bursts. ABRs were elicited by monaural right, monaural left, and binaural stimulation. Binaural interaction was investigated in two ways. First, grand averages of the binaural interaction component were computed for each age group. Second, wave V characteristics of the binaural ABR were compared with those of the summed left and right ABRs.

Results: Binaural interaction in the click ABR was demonstrated by shorter latencies and smaller amplitudes in the binaural compared with the summed monaural responses. For 500 Hz tone-burst ABR, no latency differences were found. However, amplitudes were significantly smaller in the binaural than summed monaural condition. An age-effect was found for 500 Hz tone-burst, but not for click ABR.

Conclusions: Brainstem binaural interaction seems to decline with age. Interestingly, these changes seem to be stimulus-dependent.

Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Impact of Hearing Aid Technology on Outcomes in Daily Life I: The Patients' Perspective.

Impact of Hearing Aid Technology on Outcomes in Daily Life I: The Patients' Perspective.: Objectives: One of the challenges facing hearing care providers when recommending hearing aids is the choice of device technology level. Major manufacturers market families of hearing aids that are described as spanning the range from basic technology to premium technology. Premium technology hearing aids include acoustical processing capabilities (features) that are not found in basic technology instruments. These premium features are intended to yield improved hearing in daily life compared with basic-feature devices. However, independent research that establishes the incremental effectiveness of premium-feature devices compared with basic-feature devices is lacking. This research was designed to explore reported differences in hearing abilities for adults using premium- and basic-feature hearing aids in their daily lives.

Design: This was a single-blinded, repeated, crossover trial in which the participants were blinded. All procedures were carefully controlled to limit researcher bias. Forty-five participants used carefully fitted bilateral hearing aids for 1 month and then provided data to describe the hearing improvements or deficiencies noted in daily life. Typical participants were 70 years old with mild to moderate adult-onset hearing loss bilaterally. Each participant used four pairs of hearing aids: premium- and basic-feature devices from brands marketed by each of two major manufacturers. Participants were blinded about the devices they used and about the research questions.

Results: All of the outcomes were designed to capture the participant's point of view about the benefits of the hearing aids. Three types of data were collected: change in hearing-related quality of life, extent of agreement with six positively worded statements about everyday hearing with the hearing aids, and reported preferences between the premium- and basic-feature devices from each brand as well as across all four research hearing aids combined. None of these measures yielded a statistically significant difference in outcomes between premium- and basic-feature devices. Participants did not report better outcomes with premium processing with any measure.

Conclusions: It could reasonably be asserted that the patient's perspective is the gold standard for hearing aid effectiveness. While the acoustical processing provided by premium features can potentially improve scores on tests conducted in contrived conditions in a laboratory, or on specific items in a questionnaire, this does not ensure that the processing will be of noteworthy benefit when the hearing aid is used in the real world challenges faced by the patient. If evidence suggests the patient cannot detect that premium features yield improvements over basic features in daily life, what is the responsibility of the provider in recommending hearing aid technology level? In the present research, there was no evidence to suggest that premium-feature devices yielded better outcomes than basic-feature devices from the patient's point of view. All of the research hearing aids were substantially, but equally, helpful. Further research is needed on this topic with other hearing aids and other manufacturers. In the meantime, providers should insist on scientifically credible independent evidence to support effectiveness claims for any hearing help devices.

Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Auditory Impairments in HIV-Infected Children.

Auditory Impairments in HIV-Infected Children.: Objectives: In a cross-sectional study of human immunodeficiency virus (HIV)-infected adults, the authors showed lower distortion product otoacoustic emissions (DPOAEs) in HIV+ individuals compared with controls as well as findings consistent with a central auditory processing deficit in HIV+ adults on antiretroviral therapy. The authors hypothesized that HIV+ children would also have a higher prevalence of abnormal central and peripheral hearing test results compared with HIV- controls.

Design: Pure-tone thresholds, DPOAEs, and tympanometry were performed on 244 subjects (131 HIV+ and 113 HIV- subjects). Thirty-five of the HIV+, and 3 of the HIV- subjects had a history of tuberculosis treatment. Gap detection results were available for 18 HIV- and 44 HIV+ children. Auditory brainstem response results were available for 72 HIV- and 72 HIV+ children. Data from ears with abnormal tympanograms were excluded.

Results: HIV+ subjects were significantly more likely to have abnormal tympanograms, histories of ear drainage, tuberculosis, or dizziness. All audiometric results were compared between groups using a two-way ANOVA with HIV status and ear drainage history as grouping variables. Mean audiometric thresholds, gap detection thresholds, and auditory brainstem response latencies did not differ between groups, although the HIV+ group had a higher proportion of individuals with a hearing loss >25 dB HL in the better ear. The HIV+ group had reduced DPOAE levels (p

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Nasal function and dysfunction in exercise

Review Article

Nasal function and dysfunction in exercise

A Walker^a1 c1, P Surda^a1, M Rossiter^a2 and S Little^a1

^a1 Department of ENT Surgery, St George's Hospital, London, UK

^a2 All Sports Medicine, Candover Clinic, Basingstoke and North Hampshire Hospital, Basingstoke, UK

Abstract

Background: There have been recent advances in our appreciation of the functional complementarity of the upper and lower airways. The unified airway begins at the nose: rather than acting merely as a conduit for air to the lungs, the nose and nasal cavity perform an important role in filtering, humidification and immune surveillance.

Methods: The physiological and pathological responses of the nasal cavity to exercise and regular training are examined in this narrative review, with specific reference to the relation of nasal health to quality of life, lower airway health and upper respiratory tract infections. Relevant literature is examined and placed in clinical context.

Results: There is considerable published evidence to support nasal dysfunction associated with exercise, and a link to lower airway dysfunction. Evidence also supports the role of upper and lower airway dysfunction in the development of upper respiratory tract infection symptoms.

Conclusion: Nasal dysfunction in exercise may be a source of considerable morbidity to the regular exerciser, and further research into exercise-induced rhinitis is recommended.

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Contents Vol. 25, 2015

J Mol Microbiol Biotechnol 2015;25:I-IV

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Active middle-ear implant fixation in an unusual place

Clinical Record

Active middle-ear implant fixation in an unusual place: clinical and audiological outcomes

J F Polanski^a1a2 c1, A D Soares^a1, Z M Dos Santos^a1 and O L Mendonça Cruz^a1

^a1 Department of Otolaryngology and Head and Neck Surgery, Federal University of São Paulo ('UNIFESP'), Curitiba, Brazil

^a2 Department of Otorhinolaryngology, Federal University of Parana, Curitiba, Brazil

Abstract

Objective: The Vibrant Soundbridge is an active middle-ear implant for hearing rehabilitation that is usually placed in the long process of the incus or round window. This study reports on the unusual implant attachment to the short process of the incus in a patient with ear malformation, and describes their audiological and clinical outcomes.

Methods: Case report and literature review.

Results: Audiological evaluation with the Vibrant Soundbridge implant showed a pure tone average of 31 dB. The speech test, at 65 dB HL, revealed correct recognition of 92 per cent of disyllabic words. The Glasgow Hearing Aid Benefit Profile showed high levels of satisfaction, hearing aid use and benefit.

Conclusion: Fixation of the Vibrant Soundbridge implant on the short process of the incus is a feasible option, with good clinical and audiological outcomes. Coupling the floating mass transducer to the short process of the incus is a good surgical option, especially when the long process and the oval or round window are inaccessible.

Key words

• Hearing Loss; 
• Incus; 
• Hearing Aids; 
• Middle Ear Implant

Correspondence

^c1 Address for correspondence: Dr José Fernando Polanski, Rua Des. Westphalen, 289–31, CEP: 80010-110, Curitiba, Brazil Fax: +55 41 3045 9400 E-mail: jfpolanski@gmail.com

Footnotes

  Dr J F Polanski takes responsibility for the integrity of the content of the paper

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Chemotherapy Modulates Intestinal Immune Gene Expression Including Surfactant Protein-D and Deleted in Malignant Brain Tumors 1 in Piglets

Background: Information about chemotherapy-induced intestinal gene expression may provide insight into the mechanisms underlying gut toxicity and help identify biomarkers and targets for intervention. Methods: We analyzed jejunal tissue from piglets subjected to two different, clinically relevant chemotherapy regimens: (1) busulfan plus cyclophosphamide (BUCY) and (2) doxorubicin (DOX). Results: Gene expression analysis identified 1,328 differentially expressed genes in the BUCY piglets and 594 in the DOX piglets, compared to controls. Similar changes in expression were found for 137 genes across the BUCY and DOX piglets. Selected genes of potential biological significance with a similar change in expression across the treatments were controlled by real-time polymerase chain reaction. Key innate defense molecules, including surfactant protein-D and deleted in malignant brain tumors 1, were among the upregulated genes for both treatments. Conclusion: In the developing intestine, chemotherapy increases the expression of genes related to innate immune functions involved in surveillance, protection, and homeostasis of mucosal surfaces.
Chemotherapy 2015–16;61:204–216

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A case of pharyngeal diphtheria in Germany, June 2015

Abstract

Background

In June 2015, a 45-year-old man suffering from acute necrotic tonsillitis and throat phlegmon was hospitalized in Nuremberg, Germany. After emergency surgery the patient was initially treated with antibiotics.

Results

A throat swab grew a toxigenic Corynebacterium diphtheriae biovar mitis strain. The patient's vaccination status was not documented and the patient was tested serologically for anti-diphtheria antibodies showing no protective immunity. Extensive control investigations were performed by the local health department showing no likely source of his infection.

Conclusion

No secondary cases were found and the patient completely recovered.

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A Combination of Targeted Therapy with Chemotherapy Backbone Induces Response in a Treatment-Resistant Triple-Negative MCL1-Amplified Metastatic Breast Cancer Patient

After failure of anthracycline- and platinum-based therapy, no effective therapies exist for management of metastatic triple-negative breast cancer (TNBC). We report a case of metastatic TNBC harboring MCL1 amplification, as identified by comprehensive genomic profiling in the course of clinical care. MCL1 is an antiapoptotic gene in the BCL2 family, and MCL1 amplification is common in TNBC (at least 20%). A personalized dose-reduced regimen centered on a combination of sorafenib and vorinostat was implemented, based on preclinical evidence demonstrating treatment synergy in the setting of MCL1 amplification. Although hospice care was being considered before treatment initiation, the personalized regimen yielded 6 additional months of life for this patient. Further rigorous studies are needed to confirm that this regimen or derivatives thereof can benefit the MCL1-amplified subset of TNBC patients.
Case Rep Oncol 2016;9:112-118

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Parathyroid carcinoma presenting as mandibular ulceration

Parathyroid carcinoma presenting as mandibular ulceration

via European Annals of Otorhinolaryngology, Head and Neck Diseases

Publication date: Available online 16 February 2016

 
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): Y. Oukessou, M. Ait El Kerdoudi, H. El Attar, M. Mahtar

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Osteoblastoma of the maxillary sinus in a child presenting with exophthalmos

Publication date: Available online 16 February 2016
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): O. Vella, F. Cuny, L. Robard, C. Bazille
IntroductionBenign osteoblastoma is a rare fibrous bone tumour observed in children. Very few cases involving the paranasal sinuses have been reported.SummaryA 10-year-old child presented with a 1-month history of right exophthalmos. Clinical and radiological assessment demonstrated a heterogeneous tumour with bone components occupying all of the maxillary sinus. Initial histology was in favour of fibrous dysplasia. Surgery was performed via a combined approach. After review of the histology slides, the final diagnosis was that of osteoblastoma. In view of the procedure performed and after consultation, no complementary treatment was proposed. A recurrence was observed 8months later. Right maxillectomy associated with total ethmoidectomy via a combined approach was performed to ensure complete resection of the tumour. A favourable course without recurrence was observed with a follow-up of 5 years.DiscussionOsteoblastoma of the maxillary sinus is rare. CT assessment must be as precise as possible to avoid confusion with another tumour. The diagnosis can only be confirmed by histological examination. This case report is completed by a review of the literature with description of the main differential diagnoses.

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A Review of the Literature on Extrarenal Retroperitoneal Angiomyolipoma

Background. Extrarenal retroperitoneal angiomyolipomas are rare. Aim. To review the literature. Results. Angiomyolipomas, previously classified as hamartomas, are now classified as benign tumours. Thirty cases of primary retroperitoneal angiomyolipomas have been reported. Diagnosis of the disease upon is based radiological and pathological findings of triphasic features of (a) fat and (b) blood vessels and myoid tissue. Immunohistochemistry tends to be positive for HMB45, MART1, HHF35, calponin, NKI-C3, and CD117. The lesion is common in women. Treatment options have included the following: (a) radical surgical excision of the lesion with renal sparing surgery or radical nephrectomy in cases where malignant tumours could not be excluded and (b) selective embolization of the lesion alone or prior to surgical excision. One case of retroperitoneal angiomyolipoma was reported in a patient 15 years after undergoing radical nephrectomy for angiomyolipoma of kidney and two cases of distant metastases of angiomyolipoma have been reported following radical resection of the tumour. Conclusions. With the report of two cases of metastases ensuing surgical resection of the primary lesions there is need for academic pathologists to debate and review angiomyolipomas to decide whether to reclassify angiomyolipomas as slow-growing malignant tumours or whether the reported cases of metastases were de novo tumours or metastatic lesions.

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Salicylate-Induced Hearing Loss Trigger Structural Synaptic Modifications in the Ventral Cochlear Nucleus of Rats via Medial Olivocochlear (MOC) Feedback Circuit

Abstract

Lesion-induced cochlear damage can result in synaptic outgrowth in the ventral cochlear nucleus (VCN). Tinnitus may be associated with the synaptic outgrowth and hyperactivity in the VCN. However, it remains unclear how hearing loss triggers structural synaptic modifications in the VCN of rats subjected to salicylate-induced tinnitus. To address this issue, we evaluated tinnitus-like behavior in rats after salicylate treatment and compared the amplitude of the distortion product evoked otoacoustic emission (DPOAE) and auditory brainstem response (ABR) between control and treated rats. Moreover, we observed the changes in the synaptic ultrastructure and in the expression levels of growth-associated protein (GAP-43), brain-derived neurotrophic factor (BDNF), the microglial marker Iba-1 and glial fibrillary acidic protein (GFAP) in the VCN. After salicylate treatment (300 mg/kg/day for 4 and 8 days), analysis of the gap prepulse inhibition of the acoustic startle showed that the rats were experiencing tinnitus. The changes in the DPOAE and ABR amplitude indicated an improvement in cochlear sensitivity and a reduction in auditory input following salicylate treatment. The treated rats displayed more synaptic vesicles and longer postsynaptic density in the VCN than the control rats. We observed that the GAP-43 expression, predominantly from medial olivocochlear (MOC) neurons, was significantly up-regulated, and that BDNF- and Iba-1-immunoreactive cells were persistently decreased after salicylate administration. Furthermore, GFAP-immunoreactive astrocytes, which is associated with synaptic regrowth, was significantly increased in the treated groups. Our study revealed that reduced auditory nerve activity triggers synaptic outgrowth and hyperactivity in the VCN via a MOC neural feedback circuit. Structural synaptic modifications may be a reflexive process that compensates for the reduced auditory input after salicylate administration. However, massive increases in excitatory synapses in the VCN may represent a detrimental process that causes central hyperactivity, leading to tinnitus.

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Kinetics and Molecular Docking Study of an Anti-diabetic Drug Glimepiride as Acetylcholinesterase Inhibitor: Implication for Alzheimer’s Disease-Diabetes Dual Therapy

Abstract

At the present time, treatment of two most common degenerative disorders of elderly population i.e., Type 2 Diabetes Mellitus (T2DM) and Alzheimer's disease (AD) is a major concern worldwide. As there are several evidences that proved strong linkages between these two disorders, the idea of using dual therapeutic agent for both the diseases might be considered as a good initiative. Earlier reports have revealed that oral anti-diabetic drugs such as peroxisome proliferator activated receptor γ (PPARγ) agonists (thiazolidinediones) when used in T2DM patients suffering from AD showed improved memory and cognition. However, the underlying mechanism still needs to be deciphered. Therefore, the present study was carried out to find whether glimepiride, an oral antidiabetic drug which is a PPARγ agonist could inhibit the activity of acetylcholine esterase (AChE) enzyme. Actually, AChE inhibitors seize the breakdown of acetylcholine which forms the main therapeutic strategy for AD. Here, glimepiride showed dose dependent inhibitory activity against AChE enzyme with IC50 value of 235 μM. Kinetic analysis showed competitive inhibition, which was verified by in silico docking studies. Glimepiride was found to interact with AChE enzyme at the same locus as that of substrate acetylcholine iodide (AChI). Interestingly, amino acid residues, Q71, Y72, V73, D74, W86, N87, Y124, S125, W286, F295, F297, Y337, F338 and Y341 of AChE were found to be common for 'glimepiride–AChE interaction' as well as 'AChI–AChE interaction'. Thus the present computational and kinetics study concludes that glimepiride and other thiazolidinediones derivatives could form the basis of future dual therapy against diabetes associated neurological disorders.

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Production and Characterization of Polyhydroxyalkanoates and Native Microorganisms Synthesized from Fatty Waste

Polyhydroxyalkanoates (PHAs) are biodegradable and biocompatible plastics. They are synthesized by a wide variety of microorganisms (i.e., fungi and bacteria) and some organisms such as plants, which share characteristics with petrochemical-based plastics. The most recent studies focus on finding inexpensive substrates and extraction strategies that allow reducing product costs, thus moving into a widespread market, the market for petroleum-based plastics. In this study, the production of polyhydroxybutyrate (PHB) was evaluated using the native strains, Bacillus megaterium, Bacillus sp., and Lactococcus lactis, and glycerol reagent grade (GRG), residual glycerol (RGSB) byproduct of biodiesel from palm oil, Jatropha oil, castor oil, waste frying oils, and whey as substrates. Different bacteria-substrate systems were evaluated thrice on a laboratory scale under different conditions of temperature, pH, and substrate concentration, employing 50 mL of broth in 250 mL. The bacterial growth was tested in all systems; however, the B. megaterium GRG system generated the highest accumulation of PHA. The previous approach was allowed to propose a statistical design optimization with RGSB (i.e., RGSB, 15 g/L, pH 7.0, and 25°C). This system reached 2.80 g/L of PHB yield and was the optimal condition tested; however, the optimal biomass 5.42 g/L occurs at pH 9.0 and 25°C, with a substrate concentration of 22 g/L.

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Osteoblastoma of the maxillary sinus in a child presenting with exophthalmos

Publication date: Available online 16 February 2016
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): O. Vella, F. Cuny, L. Robard, C. Bazille
IntroductionBenign osteoblastoma is a rare fibrous bone tumour observed in children. Very few cases involving the paranasal sinuses have been reported.SummaryA 10-year-old child presented with a 1-month history of right exophthalmos. Clinical and radiological assessment demonstrated a heterogeneous tumour with bone components occupying all of the maxillary sinus. Initial histology was in favour of fibrous dysplasia. Surgery was performed via a combined approach. After review of the histology slides, the final diagnosis was that of osteoblastoma. In view of the procedure performed and after consultation, no complementary treatment was proposed. A recurrence was observed 8months later. Right maxillectomy associated with total ethmoidectomy via a combined approach was performed to ensure complete resection of the tumour. A favourable course without recurrence was observed with a follow-up of 5 years.DiscussionOsteoblastoma of the maxillary sinus is rare. CT assessment must be as precise as possible to avoid confusion with another tumour. The diagnosis can only be confirmed by histological examination. This case report is completed by a review of the literature with description of the main differential diagnoses.

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Fourier-Transform Infrared Absorption Spectroscopy in Binary Hydrocarbon-Alcohol Single Droplet Evaporation

Broadband absorption spectroscopy, by way of FTIR, was used to investigate the vapor cloud of a single millimeter sized liquid droplet suspended by a syringe as it evaporates at standard conditions. Single beam data were collected every 8 seconds resulting in a time-resolved record. Species concentrations were tracked using their resonant absorption peaks and correlated with a multidimensional numerical model. The numerical model combined a Gaussian beam transmission through a temporally changing spherical vapor cloud with radial concentration gradients, informed by the law and interpreted using the Abel transform. There was fair agreement with temporal evaporation trends for single component runs. Multicomponent experiments of ethanol and isooctane showed synergistic blending effects and preferential evaporation of ethanol. Droplets were also suspended by a thermocouple to track the droplet temperature over time as they were subject to evaporative cooling. This work is the foundation of a basic technique for collecting useful data to inform a complex transport problem.

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T Cell Response in Patients with Implanted Biological and Mechanical Prosthetic Heart Valves

The study was aimed at assessing T cell subsets of peripheral blood from recipients of long-term functioning (more than 60 months) biological and mechanical heart valve prostheses. The absolute and relative number of CD4 and CD8 T cell subsets was analyzed: naïve (N, CD45RA+CD62L+), central memory (CM, CD45RA−CD62L+), effector memory (EM, CD45RA−CD62L−), and terminally differentiated CD45RA-positive effector memory (TEMRA, CD45RA+CD62L−) in 25 persons with biological and 7 with mechanical prosthesis compared with 48 apparently healthy volunteers. The relative and absolute number of central memory and naïve CD3+CD8+ in patients with biological prosthesis was decreased (). Meanwhile the number of CD45RA+CD62L−CD3+CD8+ and CD3+CD4+ was increased (). Patients with mechanical prosthesis had increased absolute and relative number of CD45RA+CD62L−CD3+CD8+ cells (). Also the relative number of CD3+CD4+ cells was reduced (). We assume that altered composition of T cell subsets points at development of xenograft rejection reaction against both mechanical and biological heart valve prostheses.

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Proof-of Concept that an Acute Trophic Factors Intervention After Spinal Cord Injury Provides an Adequate Niche for Neuroprotection, Recruitment of Nestin-Expressing Progenitors and Regeneration

Abstract

Trophic factor treatment has been shown to improve the recovery of brain and spinal cord injury (SCI). In this study, we examined the effects of TSC1 (a combination of insulin-like growth factor 1 and transferrin) 4 and 8 h after SCI at the thoracic segment level (T12) in nestin-GFP transgenic mice. TSC1 treatment for 4 and 8 h increased the number of nestin-expressing cells around the lesion site and prevented Wallerian degeneration. Treatment with TSC1 for 4 h significantly increased heat shock protein (HSP)-32 and HSP-70 expression 1 and 2 mm from lesion site (both, caudal and rostral). Conversely, the number of HSP-32 positive cells decreased after an 8-h TSC1 treatment, although it was still higher than in both, non-treated SCI and intact spinal cord animals. Furthermore, TSC1 increased NG2 expressing cell numbers and preserved most axons intact, facilitating remyelination and repair. These results support our hypothesis that TSC1 is an effective treatment for cell and tissue neuroprotection after SCI. An early intervention is crucial to prevent secondary damage of the injured SC and, in particular, to prevent Wallerian degeneration.

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Benington schoolboy flies to the USA for specialist cancer treatment – Hertfordshire Mercury

Benington schoolboy flies to the USA for specialist cancer treatment Hertfordshire Mercury Brave schoolboy Benjamin Carter has flown out to the United States for a specialist cancer treatment not available in the UK. The 11-year-old, of Walkern Road, Benington, suffers from rhabdomyosarcoma (RMS), which affects the muscle tissue in his larynx.

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Pharmaceutics, Vol. 8, Pages 4: Microarray Analysis of Differentially-Expressed Genes Encoding CYP450 and Phase II Drug Metabolizing Enzymes in Psoriasis and Melanoma

Cytochrome P450 drug metabolizing enzymes are implicated in personalized medicine for two main reasons. First, inter-individual variability in CYP3A4 expression is a confounding factor during cancer treatment. Second, inhibition or induction of CYP3A4 can trigger adverse drug–drug interactions. However, inflammation can downregulate CYP3A4 and other drug metabolizing enzymes and lead to altered metabolism of drugs and essential vitamins and lipids. Little is known about effects of inflammation on expression of CYP450 genes controlling drug metabolism in the skin. Therefore, we analyzed seven published microarray datasets, and identified differentially-expressed genes in two inflammatory skin diseases (melanoma and psoriasis). We observed opposite patterns of expression of genes regulating metabolism of specific vitamins and lipids in psoriasis and melanoma samples. Thus, genes controlling the turnover of vitamin D (CYP27B1, CYP24A1), vitamin A (ALDH1A3, AKR1B10), and cholesterol (CYP7B1), were up-regulated in psoriasis, whereas melanomas showed downregulation of genes regulating turnover of vitamin A (AKR1C3), and cholesterol (CYP39A1). Genes controlling abnormal keratinocyte differentiation and epidermal barrier function (CYP4F22, SULT2B1) were up-regulated in psoriasis. The up-regulated CYP24A1, CYP4F22, SULT2B1, and CYP7B1 genes are potential drug targets in psoriatic skin. Both disease samples showed diminished drug metabolizing capacity due to downregulation of the CYP1B1 and CYP3A5 genes. However, melanomas showed greater loss of drug metabolizing capacity due to downregulation of the CYP3A4 gene.

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Evaluation of Malignancy Grade of Breast Cancer Using Perflubutane-Enhanced Ultrasonography

Publication date: Available online 16 February 2016
Source:Ultrasound in Medicine & Biology
Author(s): Norio Masumoto, Takayuki Kadoya, Ai Amioka, Keiko Kajitani, Hideo Shigematsu, Akiko Emi, Kazuo Matsuura, Koji Arihiro, Morihito Okada
Whether the contrast effects of perflubutane on contrast-enhanced ultrasonography can predict the malignancy grade of breast cancer is unknown. We analyzed associations between perfusion parameters created from time–intensity curves based on enhancement intensity and temporal changes in contrast-enhanced ultrasonography and clinicopathologic factors in 100 consecutive patients with invasive breast cancer. Values of perfusion parameters were significantly greater in estrogen receptor-negative than -positive tumors (peak intensity, p = 0.0002; ascending slope, p = 0.006; area under the curve, p = 0.0006). Variations in the peak intensity of Ki-67 were significantly correlated in all tumors (r = 0.54, p < 0.0001) and in luminal (r = 0.43, p = 0.0002), human epidermal growth factor receptor type 2-positive (r = 0.47, p = 0.047) and triple-negative (r = 0.55, p = 0.043) tumors. Perfusion parameters on contrast-enhanced ultrasonography can provide excellent predictive value for high-grade malignancy and might help to determine appropriate therapeutic strategies.

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Influence of Type 2 Diabetes on Prevalence of Key Periodontal Pathogens, Salivary Matrix Metalloproteinases, and Bone Remodeling Markers in Sudanese Adults with and without Chronic Periodontitis

This study compared the influence of type 2 diabetes on the occurrence of six periodontal pathogens in plaque samples of patients with and without chronic periodontitis. Levels of salivary MMP-8, MMP-9, RANKL, and OPG were also investigated. The study enrolled 31 patients with type 2 diabetes and chronic periodontitis (DM + CP), 29 with chronic periodontitis (CP), and 20 with type 2 diabetes (DM). Questionnaire-guided interviews were conducted and plaque index, bleeding on probing, and pocket depth were recorded. Polymerase chain reaction (PCR) was utilized to determine the prevalence of the bacteria. The levels of salivary molecules were determined by enzyme immunosorbent assay (ELISA). The CP group had the highest prevalence of P. gingivalis (81.5%), followed by the DM + CP (59.3%) and DM (55.0%) groups (). Similar trends were observed for P. intermedia and T. denticola. The prevalence of T. forsythia was 100% in both periodontitis groups compared to 90% in the DM group. There were no significant differences between the groups regarding the concentrations of MMP-8, MMP-9, or OPG. RANKL concentrations were below the detection limit. Our data show that type 2 diabetes has no significant influence on the prevalence of the investigated periodontal pathogens, or the levels of salivary MMP-8, MMP-9, and OPG.

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Pulsatile tinnitus and a temporal bone mass

Publication date: Available online 16 February 2016
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): D.T. Ginat, M.B. Gluth

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Osteoblastoma of the maxillary sinus in a child presenting with exophthalmos

Publication date: Available online 16 February 2016
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): O. Vella, F. Cuny, L. Robard, C. Bazille
IntroductionBenign osteoblastoma is a rare fibrous bone tumour observed in children. Very few cases involving the paranasal sinuses have been reported.SummaryA 10-year-old child presented with a 1-month history of right exophthalmos. Clinical and radiological assessment demonstrated a heterogeneous tumour with bone components occupying all of the maxillary sinus. Initial histology was in favour of fibrous dysplasia. Surgery was performed via a combined approach. After review of the histology slides, the final diagnosis was that of osteoblastoma. In view of the procedure performed and after consultation, no complementary treatment was proposed. A recurrence was observed 8months later. Right maxillectomy associated with total ethmoidectomy via a combined approach was performed to ensure complete resection of the tumour. A favourable course without recurrence was observed with a follow-up of 5 years.DiscussionOsteoblastoma of the maxillary sinus is rare. CT assessment must be as precise as possible to avoid confusion with another tumour. The diagnosis can only be confirmed by histological examination. This case report is completed by a review of the literature with description of the main differential diagnoses.

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ESUS: Fire and forget? So einfach ist das nicht

Kryptogener Insult
Bis zu zwei Drittel der Patienten mit kryptogenem Schlaganfall entwickeln ein Vorhofflimmern – wenn man nur lange genug danach sucht. Sollte man die Suche also nicht besser lassen und gleich antikoagulieren?

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Parathyroid carcinoma presenting as mandibular ulceration

Publication date: Available online 16 February 2016
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): Y. Oukessou, M. Ait El Kerdoudi, H. El Attar, M. Mahtar

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A rare cause of exophthalmos in children

Publication date: Available online 16 February 2016
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): N. Kolsi, Z. B-Rhaiem, J. Koubaa

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Parathyroid carcinoma presenting as mandibular ulceration

Publication date: Available online 16 February 2016
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): Y. Oukessou, M. Ait El Kerdoudi, H. El Attar, M. Mahtar

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Pulsatile tinnitus and a temporal bone mass

Publication date: Available online 16 February 2016
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): D.T. Ginat, M.B. Gluth

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GSE71559 Sexual polyploidization in Medicago sativa L.: impact on the phenotype, gene transcription and genome methylation

Contributors : Daniele Rosellini ; Nicoletta Ferradini ; Stefano Allegrucci ; Stefano Capomaccio ; Elisa D Zago ; Paola Leonetti ; Bachir Balech ; Riccardo Aversano ; Domenico Carputo ; Lara Reale ; Fabio Veronesi
Series Type : Expression profiling by array
Organism : Medicago sativa ; Medicago truncatula

Polyploidization as the consequence of 2n gamete formation is a prominent mechanism in plant evolution. Studying its effects on the genome and its expression has both basic and applied interest. We crossed two diploid (2n=2x=16) M. sativa plants, a subsp. falcata seed parent and a coerulea x falcata pollen parent that produce a mixture of n and 2n eggs and pollen, respectively. Such cross produced full-sib diploid and tetraploid (2n=4x=32) progenies, the latter being the result of bilateral sexual polyploidization (BSP). These unique materials allowed us to investigate the effects of BSP, and separating the effect of intraspecific hybridization from those of polyploidization by comparing 2x with 4x full sib progeny plants. SSR marker segregation demonstrated tetrasomic inheritance for all chromosomes but one, demonstrating that these neotetraploids are true autotetraploids. BSP brought about increased biomass, earlier flowering, higher seed set and weight, larger leaves with larger cells. Microarray analyses with M. truncatula gene chips showed that several hundred genes, related to diverse metabolic functions, changed their expression level as a consequence of polyploidization. In addition, cytosine methylation increased in 2x but not in 4x hybrids. Our results indicate that sexual polyploidization induce significant transcriptional novelty, possibly mediated in part by DNA methylation, and phenotypic novelty that can be at the base of improved adaptation and reproductive success of tetraploid M. sativa with respect to its diploid progenitor. These polyploidy-induced changes may have promoted the adoption of tetraploid alfalfa in agriculture.

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Salicylate-Induced Hearing Loss Trigger Structural Synaptic Modifications in the Ventral Cochlear Nucleus of Rats via Medial Olivocochlear (MOC) Feedback Circuit

Abstract

Lesion-induced cochlear damage can result in synaptic outgrowth in the ventral cochlear nucleus (VCN). Tinnitus may be associated with the synaptic outgrowth and hyperactivity in the VCN. However, it remains unclear how hearing loss triggers structural synaptic modifications in the VCN of rats subjected to salicylate-induced tinnitus. To address this issue, we evaluated tinnitus-like behavior in rats after salicylate treatment and compared the amplitude of the distortion product evoked otoacoustic emission (DPOAE) and auditory brainstem response (ABR) between control and treated rats. Moreover, we observed the changes in the synaptic ultrastructure and in the expression levels of growth-associated protein (GAP-43), brain-derived neurotrophic factor (BDNF), the microglial marker Iba-1 and glial fibrillary acidic protein (GFAP) in the VCN. After salicylate treatment (300 mg/kg/day for 4 and 8 days), analysis of the gap prepulse inhibition of the acoustic startle showed that the rats were experiencing tinnitus. The changes in the DPOAE and ABR amplitude indicated an improvement in cochlear sensitivity and a reduction in auditory input following salicylate treatment. The treated rats displayed more synaptic vesicles and longer postsynaptic density in the VCN than the control rats. We observed that the GAP-43 expression, predominantly from medial olivocochlear (MOC) neurons, was significantly up-regulated, and that BDNF- and Iba-1-immunoreactive cells were persistently decreased after salicylate administration. Furthermore, GFAP-immunoreactive astrocytes, which is associated with synaptic regrowth, was significantly increased in the treated groups. Our study revealed that reduced auditory nerve activity triggers synaptic outgrowth and hyperactivity in the VCN via a MOC neural feedback circuit. Structural synaptic modifications may be a reflexive process that compensates for the reduced auditory input after salicylate administration. However, massive increases in excitatory synapses in the VCN may represent a detrimental process that causes central hyperactivity, leading to tinnitus.

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Proof-of Concept that an Acute Trophic Factors Intervention After Spinal Cord Injury Provides an Adequate Niche for Neuroprotection, Recruitment of Nestin-Expressing Progenitors and Regeneration

Abstract

Trophic factor treatment has been shown to improve the recovery of brain and spinal cord injury (SCI). In this study, we examined the effects of TSC1 (a combination of insulin-like growth factor 1 and transferrin) 4 and 8 h after SCI at the thoracic segment level (T12) in nestin-GFP transgenic mice. TSC1 treatment for 4 and 8 h increased the number of nestin-expressing cells around the lesion site and prevented Wallerian degeneration. Treatment with TSC1 for 4 h significantly increased heat shock protein (HSP)-32 and HSP-70 expression 1 and 2 mm from lesion site (both, caudal and rostral). Conversely, the number of HSP-32 positive cells decreased after an 8-h TSC1 treatment, although it was still higher than in both, non-treated SCI and intact spinal cord animals. Furthermore, TSC1 increased NG2 expressing cell numbers and preserved most axons intact, facilitating remyelination and repair. These results support our hypothesis that TSC1 is an effective treatment for cell and tissue neuroprotection after SCI. An early intervention is crucial to prevent secondary damage of the injured SC and, in particular, to prevent Wallerian degeneration.

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Kinetics and Molecular Docking Study of an Anti-diabetic Drug Glimepiride as Acetylcholinesterase Inhibitor: Implication for Alzheimer’s Disease-Diabetes Dual Therapy

Abstract

At the present time, treatment of two most common degenerative disorders of elderly population i.e., Type 2 Diabetes Mellitus (T2DM) and Alzheimer's disease (AD) is a major concern worldwide. As there are several evidences that proved strong linkages between these two disorders, the idea of using dual therapeutic agent for both the diseases might be considered as a good initiative. Earlier reports have revealed that oral anti-diabetic drugs such as peroxisome proliferator activated receptor γ (PPARγ) agonists (thiazolidinediones) when used in T2DM patients suffering from AD showed improved memory and cognition. However, the underlying mechanism still needs to be deciphered. Therefore, the present study was carried out to find whether glimepiride, an oral antidiabetic drug which is a PPARγ agonist could inhibit the activity of acetylcholine esterase (AChE) enzyme. Actually, AChE inhibitors seize the breakdown of acetylcholine which forms the main therapeutic strategy for AD. Here, glimepiride showed dose dependent inhibitory activity against AChE enzyme with IC50 value of 235 μM. Kinetic analysis showed competitive inhibition, which was verified by in silico docking studies. Glimepiride was found to interact with AChE enzyme at the same locus as that of substrate acetylcholine iodide (AChI). Interestingly, amino acid residues, Q71, Y72, V73, D74, W86, N87, Y124, S125, W286, F295, F297, Y337, F338 and Y341 of AChE were found to be common for 'glimepiride–AChE interaction' as well as 'AChI–AChE interaction'. Thus the present computational and kinetics study concludes that glimepiride and other thiazolidinediones derivatives could form the basis of future dual therapy against diabetes associated neurological disorders.

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Salicylate-Induced Hearing Loss Trigger Structural Synaptic Modifications in the Ventral Cochlear Nucleus of Rats via Medial Olivocochlear (MOC) Feedback Circuit

Abstract

Lesion-induced cochlear damage can result in synaptic outgrowth in the ventral cochlear nucleus (VCN). Tinnitus may be associated with the synaptic outgrowth and hyperactivity in the VCN. However, it remains unclear how hearing loss triggers structural synaptic modifications in the VCN of rats subjected to salicylate-induced tinnitus. To address this issue, we evaluated tinnitus-like behavior in rats after salicylate treatment and compared the amplitude of the distortion product evoked otoacoustic emission (DPOAE) and auditory brainstem response (ABR) between control and treated rats. Moreover, we observed the changes in the synaptic ultrastructure and in the expression levels of growth-associated protein (GAP-43), brain-derived neurotrophic factor (BDNF), the microglial marker Iba-1 and glial fibrillary acidic protein (GFAP) in the VCN. After salicylate treatment (300 mg/kg/day for 4 and 8 days), analysis of the gap prepulse inhibition of the acoustic startle showed that the rats were experiencing tinnitus. The changes in the DPOAE and ABR amplitude indicated an improvement in cochlear sensitivity and a reduction in auditory input following salicylate treatment. The treated rats displayed more synaptic vesicles and longer postsynaptic density in the VCN than the control rats. We observed that the GAP-43 expression, predominantly from medial olivocochlear (MOC) neurons, was significantly up-regulated, and that BDNF- and Iba-1-immunoreactive cells were persistently decreased after salicylate administration. Furthermore, GFAP-immunoreactive astrocytes, which is associated with synaptic regrowth, was significantly increased in the treated groups. Our study revealed that reduced auditory nerve activity triggers synaptic outgrowth and hyperactivity in the VCN via a MOC neural feedback circuit. Structural synaptic modifications may be a reflexive process that compensates for the reduced auditory input after salicylate administration. However, massive increases in excitatory synapses in the VCN may represent a detrimental process that causes central hyperactivity, leading to tinnitus.

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Proof-of Concept that an Acute Trophic Factors Intervention After Spinal Cord Injury Provides an Adequate Niche for Neuroprotection, Recruitment of Nestin-Expressing Progenitors and Regeneration

Abstract

Trophic factor treatment has been shown to improve the recovery of brain and spinal cord injury (SCI). In this study, we examined the effects of TSC1 (a combination of insulin-like growth factor 1 and transferrin) 4 and 8 h after SCI at the thoracic segment level (T12) in nestin-GFP transgenic mice. TSC1 treatment for 4 and 8 h increased the number of nestin-expressing cells around the lesion site and prevented Wallerian degeneration. Treatment with TSC1 for 4 h significantly increased heat shock protein (HSP)-32 and HSP-70 expression 1 and 2 mm from lesion site (both, caudal and rostral). Conversely, the number of HSP-32 positive cells decreased after an 8-h TSC1 treatment, although it was still higher than in both, non-treated SCI and intact spinal cord animals. Furthermore, TSC1 increased NG2 expressing cell numbers and preserved most axons intact, facilitating remyelination and repair. These results support our hypothesis that TSC1 is an effective treatment for cell and tissue neuroprotection after SCI. An early intervention is crucial to prevent secondary damage of the injured SC and, in particular, to prevent Wallerian degeneration.

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Pharmaceutics, Vol. 8, Pages 4: Microarray Analysis of Differentially-Expressed Genes Encoding CYP450 and Phase II Drug Metabolizing Enzymes in Psoriasis and Melanoma

Cytochrome P450 drug metabolizing enzymes are implicated in personalized medicine for two main reasons. First, inter-individual variability in CYP3A4 expression is a confounding factor during cancer treatment. Second, inhibition or induction of CYP3A4 can trigger adverse drug–drug interactions. However, inflammation can downregulate CYP3A4 and other drug metabolizing enzymes and lead to altered metabolism of drugs and essential vitamins and lipids. Little is known about effects of inflammation on expression of CYP450 genes controlling drug metabolism in the skin. Therefore, we analyzed seven published microarray datasets, and identified differentially-expressed genes in two inflammatory skin diseases (melanoma and psoriasis). We observed opposite patterns of expression of genes regulating metabolism of specific vitamins and lipids in psoriasis and melanoma samples. Thus, genes controlling the turnover of vitamin D (CYP27B1, CYP24A1), vitamin A (ALDH1A3, AKR1B10), and cholesterol (CYP7B1), were up-regulated in psoriasis, whereas melanomas showed downregulation of genes regulating turnover of vitamin A (AKR1C3), and cholesterol (CYP39A1). Genes controlling abnormal keratinocyte differentiation and epidermal barrier function (CYP4F22, SULT2B1) were up-regulated in psoriasis. The up-regulated CYP24A1, CYP4F22, SULT2B1, and CYP7B1 genes are potential drug targets in psoriatic skin. Both disease samples showed diminished drug metabolizing capacity due to downregulation of the CYP1B1 and CYP3A5 genes. However, melanomas showed greater loss of drug metabolizing capacity due to downregulation of the CYP3A4 gene.

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Hereditary angioedema in a Jordanian family with a novel missense mutation in the C1-inhibitor N-terminal domain

Publication date: March 2016
Source:Molecular Immunology, Volume 71
Author(s): Saied A Jaradat, Sonia Caccia, Rifaat Rawashdeh, Motasem Melhem, Ali Al-Hawamdeh, Thomas Carzaniga, Hazem Haddad
Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) is an autosomal dominant disease caused by mutations in the SERPING1 gene. A Jordanian family, including 14 individuals with C1-INH-HAE clinical symptoms, was studied. In the propositus and his parents, SERPING1 had four mutations leading to amino acid substitutions. Two are known polymorphic variants (c.167T>C; p.Val34Ala and c.1438G>A; p.Val458Met), the others are newly described. One (c.203C>T; p.Thr46Ile) is located in the N-terminal domain of the C1-inhibitor protein and segregates with angioedema symptoms in the family. The other (c.800C>T; p.Ala245Val) belongs to the serpin domain, and derives from the unaffected father. DNA from additional 24 family members were screened for c.203C>T mutation in the target gene. All individuals heterozygous for the c.203C>T mutation had antigenic and functional plasma levels of C1-inhibitor below 50% of normal, confirming the diagnosis of type I C1-INH-HAE. Angioedema symptoms were present in 14 of 16 subjects carrier for the c.203T allele. Among these subjects, those carrying the c.800T variation had more severe and frequent symptoms than subjects without this mutation. This family-based study provides the first evidence that multiple amino acid substitutions in SERPING1 could influence C1-INH-HAE phenotype.



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Complement gene variants determine the risk of immunoglobulin-associated MPGN and C3 glomerulopathy and predict long-term renal outcome

Publication date: March 2016
Source:Molecular Immunology, Volume 71
Author(s): Paraskevas Iatropoulos, Marina Noris, Caterina Mele, Rossella Piras, Elisabetta Valoti, Elena Bresin, Manuela Curreri, Elena Mondo, Anna Zito, Sara Gamba, Serena Bettoni, Luisa Murer, Veronique Fremeaux-Bacchi, Marina Vivarelli, Francesco Emma, Erica Daina, Giuseppe Remuzzi
BackgroundMembranoproliferative glomerulonephritis (MPGN) is an uncommon cause of chronic nephropathy recently reclassified into immunoglobulin-associated MPGN (Ig-MPGN) and C3 glomerulopathy (C3G). In this study we aimed: (1) to evaluate the complement genetic and biochemical profile in patients with Ig-MPGN/C3G; (2) to investigate whether genetic variants and different patterns of complement activation (i.e., fluid versus solid phase) correlate with disease manifestations and outcomes.MethodsIn 140 patients with idiopathic Ig-MPGN or C3G we performed complement biochemical and genetic screening and correlated genetic, biochemical and histology data with clinical features.ResultsMutations in genes encoding alternative pathway complement proteins were found in both Ig-MPGN and C3G, and mutations in the two components of the C3 convertase are the most prevalent. We also report a mutation in THBD encoding thrombomodulin in a C3G patient. The presence of mutations alone does not significantly increase the risk of Ig-MPGN or C3G, but it does so when combined with common susceptibility variants (CD46 c.-366A in Ig-MPGN; CFH V62 and THBD A473 in C3G). Finally, patients without complement gene mutations or C3NeFs – autoantibodies that stabilize the alternative pathway C3 convertase – have a higher risk of progressing to end-stage renal disease than patients with identified mutations and/or C3NeFs, suggesting the existence of different pathogenetic mechanisms that lead to renal disease.ConclusionsWe provide new insights into the pathogenesis of Ig-MPGN/C3G that underscore the complex nature of these diseases and suggest that the current C3G classification may miss many cases associated with abnormalities of the complement alternative pathway.



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Ηλεκτρισμός εγκεφάλου – Επιληψία

Ο εγκέφαλος διαθέτει, όσο οι νευρώνες του είναι ζωντανοί, ένα ηλεκτρικό φορτίο που κυκλοφορεί με τη «μορφή» βιοηλεκτρικού ρεύματος. Σε φυσιολογικές καταστάσεις ζωής, το ηλεκτρικό ρεύμα αυτό φροντίζει όχι μόνο για την ήρεμη λειτουργία του εγκεφάλου αλλά και τη διατήρηση της ύπαρξής του. Τοπικές ή γενικευμένες διαταραχές του βιοηλεκτρικού αυτού ρεύματος, προκαλούν άμεσα λειτουργικές διαταραχές […]

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Hereditary angioedema in a Jordanian family with a novel missense mutation in the C1-inhibitor N-terminal domain

Publication date: March 2016
Source:Molecular Immunology, Volume 71
Author(s): Saied A Jaradat, Sonia Caccia, Rifaat Rawashdeh, Motasem Melhem, Ali Al-Hawamdeh, Thomas Carzaniga, Hazem Haddad
Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) is an autosomal dominant disease caused by mutations in the SERPING1 gene. A Jordanian family, including 14 individuals with C1-INH-HAE clinical symptoms, was studied. In the propositus and his parents, SERPING1 had four mutations leading to amino acid substitutions. Two are known polymorphic variants (c.167T>C; p.Val34Ala and c.1438G>A; p.Val458Met), the others are newly described. One (c.203C>T; p.Thr46Ile) is located in the N-terminal domain of the C1-inhibitor protein and segregates with angioedema symptoms in the family. The other (c.800C>T; p.Ala245Val) belongs to the serpin domain, and derives from the unaffected father. DNA from additional 24 family members were screened for c.203C>T mutation in the target gene. All individuals heterozygous for the c.203C>T mutation had antigenic and functional plasma levels of C1-inhibitor below 50% of normal, confirming the diagnosis of type I C1-INH-HAE. Angioedema symptoms were present in 14 of 16 subjects carrier for the c.203T allele. Among these subjects, those carrying the c.800T variation had more severe and frequent symptoms than subjects without this mutation. This family-based study provides the first evidence that multiple amino acid substitutions in SERPING1 could influence C1-INH-HAE phenotype.



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Complement gene variants determine the risk of immunoglobulin-associated MPGN and C3 glomerulopathy and predict long-term renal outcome

Publication date: March 2016
Source:Molecular Immunology, Volume 71
Author(s): Paraskevas Iatropoulos, Marina Noris, Caterina Mele, Rossella Piras, Elisabetta Valoti, Elena Bresin, Manuela Curreri, Elena Mondo, Anna Zito, Sara Gamba, Serena Bettoni, Luisa Murer, Veronique Fremeaux-Bacchi, Marina Vivarelli, Francesco Emma, Erica Daina, Giuseppe Remuzzi
BackgroundMembranoproliferative glomerulonephritis (MPGN) is an uncommon cause of chronic nephropathy recently reclassified into immunoglobulin-associated MPGN (Ig-MPGN) and C3 glomerulopathy (C3G). In this study we aimed: (1) to evaluate the complement genetic and biochemical profile in patients with Ig-MPGN/C3G; (2) to investigate whether genetic variants and different patterns of complement activation (i.e., fluid versus solid phase) correlate with disease manifestations and outcomes.MethodsIn 140 patients with idiopathic Ig-MPGN or C3G we performed complement biochemical and genetic screening and correlated genetic, biochemical and histology data with clinical features.ResultsMutations in genes encoding alternative pathway complement proteins were found in both Ig-MPGN and C3G, and mutations in the two components of the C3 convertase are the most prevalent. We also report a mutation in THBD encoding thrombomodulin in a C3G patient. The presence of mutations alone does not significantly increase the risk of Ig-MPGN or C3G, but it does so when combined with common susceptibility variants (CD46 c.-366A in Ig-MPGN; CFH V62 and THBD A473 in C3G). Finally, patients without complement gene mutations or C3NeFs – autoantibodies that stabilize the alternative pathway C3 convertase – have a higher risk of progressing to end-stage renal disease than patients with identified mutations and/or C3NeFs, suggesting the existence of different pathogenetic mechanisms that lead to renal disease.ConclusionsWe provide new insights into the pathogenesis of Ig-MPGN/C3G that underscore the complex nature of these diseases and suggest that the current C3G classification may miss many cases associated with abnormalities of the complement alternative pathway.



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