Intrafamilial variability of XYLT2-related spondyloocular syndrome

Spondyloocular syndrome is characterized by generalized osteoporosis, multiple fractures and severe ocular findings. The causative XYLT2 mutations have recently been identified with the use of whole exome sequencing. We report on two siblings with spondyloocular syndrome who presented with varying clinical severity. A novel XYLT2 missense mutation was detected in a region evolutionary conserved across the species. This report along with the previous reports demonstrates that variable expressivity may be possible even within the same family. These two siblings with a novel mutation further expand the clinical and mutational spectrum of spondyloocular syndrome.     

Evidence-based recommendations for the management of ankylosing spondylitis: systematic literature search of the 3E Initiative in Rheumatology involving a broad panel of experts and practising rheumatologists

Objective. Recommendations and/or guidelines represent a popularway of integrating evidence-based medicine into clinical practice.The 3E Initiatives is a multi-national effort to develop recommendationsfor the management of rheumatic diseases, which involves a largenumber of experts combined with practising rheumatologists addressingspecific questions relevant to clinical practice. Methods. Ten countries participated in three rounds of discussionsand votes concerning the management of AS. A set of nine questionswas formulated in the domains of diagnosis, monitoring and treatment,after a Delphi procedure. A literature search in MedLine wasconducted. Predefined outcome parameters for the domains ofdiagnosis, monitoring and treatment were assessed. The evidenceto support each proposition was evaluated and scored. Afterdiscussion and votes, the final recommendations were presentedusing brief statements by each national group, following whichthe final international recommendations were formulated. Results. A total of 2699 papers were found and 467 were selectedfor analysis. Twelve key recommendations were developed: threein the domain of diagnosis addressing general diagnostic considerations,early AS diagnosis and general practitioners’ referralrecommendations; three concerning monitoring of AS disease activity,severity and prognosis; six concerning pharmacological treatment(except biologics): non-steroidal anti-inflammatory drugs/COX-IIinhibitors, bisphosphonates and treatment of enthesitis. Thecompiled agreement among experts ranged from 72% to 93%. Conclusion. Recommendations for the management of AS were developedusing an evidence-based approach followed by expert/physicianconsensus with high level of agreement. Involvement of a largerand more representative group of rheumatologists may improvetheir dissemination and implementation in daily clinical practice. KEY WORDS: Ankylosing spondylitis, Systemic literature search, Recommendations, Non-steroidal anti-inflammatory drugs, COX-II inhibitors, Monitoring, Diagnosis, Treatment     

Dense eosinophilic infiltration of the mucosa preceding ulcerative colitis and mimicking eosinophilic colitis: report of two cases.

There is increasing evidence about the involvement of eosinophils in the pathogenesis of inflammatory bowel disease. We report here two patients with ulcerative colitis who were initially diagnosed as eosinophilic colitis based on histopathological examination during their first attacks. They had symptomatic improvement with ketotifen and metronidazole during their first attacks. However, subsequent attacks which were histopathologically diagnosed as ulcerative colitis did not resolve with the above-mentioned treatment and necessitated a treatment with 5-ASA agents plus corticosteroids. Azathioprine also had to be added in the treatment of the second patient. Dense eosinophilic infiltration in these cases may suggest a role of eosinophils in the initiation of attacks in some ulcerative colitis patients.     

Lack of association of hepatic estrogen receptor-alpha expression with histopathological and biochemical findings in chronic hepatitis C

Estrogens exert a protective effect against hepatic steatosis and fibrosis. Loss of estrogen receptor-alpha (ER-α) in the liver is associated with hepatic steatosis and inflammation in animal models. We conducted a study in order to investigate the presence and extent of ER-α expression in HCV infection, and its relationship with histological and biochemical findings. Ninety biopsy-proven chronic hepatitis C (CHC) patients were enrolled in the study. Liver biopsy specimens were immunohistochemically stained for ER-α expression. Nuclear ER-α expression percentage was calculated. ER-α was positive in 69 of the patients (76%). ER-α positive and negative groups were not significantly different in terms of age, gender, necroinflammatory activity, fibrosis, steatosis, serum levels of AST, ALT, ALP, GGT, and bilirubin. ER-α expression percentage was not correlated with fibrosis, steatosis, necroinflammatory activity and biochemical findings. Although estrogens are known to be protective against fibrosis and steatosis in animal models, we did not find any significant correlation between ER-α expression and histopathological and biochemical findings in CHC patients. These findings should be verified in further large scale studies.     

Adipokines and Systemic Inflammation in Weight-Losing Lung Cancer Patients

Background  

Cancer cachexia is a devastating condition leading to loss of function and independence, decreased performance status, decreased quality of life, and poor prognosis. Adipokines play a role in a wide variety of physiological or pathological processes, including immunity and inflammation, in addition to having significant effects on metabolism and lipogenesis. The objective of the present study was to investigate the relationship of adipokines and systemic inflammation in weight-losing advanced-stage non-small-cell lung cancer (NSCLC) patients.     

Low level of Nesfatin-1 is associated with gestational diabetes mellitus

Introduction: Gestational diabetes mellitus (GDM) occurs in ～10–25% of pregnancies. Nesfatin-1, plays a role in carbohydrate metabolism by inhibiting glucagon secretion, besides has a glucose-dependent insulinotropic effect. Explanation of the GDM pathogenesis is important due to preventing gestational complications. We aimed to investigate relationship between GDM and Nesfatin-1.

Material and methods: Seventy-nine pregnant subjects were randomly allocated to either GDM group (GDG, n?=?38) or control group (CG, n?=?41). For GDM diagnosis, 50 and 100?g oral glucose tolerance test (OGTT) were used. Nesfatin-1, insulin and other parameters were measured for all subjects. The homeostasis model assessment-insulin resistance (HOMA-IR) was calculated.

Results: Nesfatin-1 was found lower and insulin was found higher in GDG than CG. Negative correlation has been founded between Nesfatin-1 with weight, BMI, fasting glucose, serum glucose level at first hour of the 50?g OGTT and HOMA-IR.

Conclusion: In this study, patients with GDM had lower Nesfatin-1 levels than without GDM. Therefore, when the Nesfatin-1 effects on the GDM pathogenesis is clear, it may be contributed to diagnosis and treatment of the GDM.     

Development of Orally Applicable,Combinatorial Drug–Loaded Nanoparticles for the Treatment of Fibrosarcoma

Nanoparticulate systems have been receiving a significant attention especially for the treatment of cancer but one of the main hurdles is to produce these developed and high-tech nanosystems in large quantities. Anticancer drug formulations are generally designed for parenteral administrations but oral administration is still the most convenient route. In this study, orally applicable nano-sized chitosan nanoparticles (NPs) were successfully prepared using Nano Spray Dryer. It is possible to produce these NPs in large quantities by simply increasing the processing time using the machine without changing any parameter. A chemotherapeutic agent (imatinib mesylate; IMA) and nonsteroidal anti-inflammatory drug (dexketoprofen trometamol) were loaded together in these NPs. NPs were also functionalized with polyethylene glycol and folic acid to obtain long circulating NPs and tumor targeting. The antitumoral activities of formulations showed that these developed NPs can enhance the effectiveness. Animal experiments were performed on fibrosarcoma-bearing mice model, and the treatment with 0.8 mg/μL/kg IMA-loaded chitosan NPs was found to be successful to slow down the growth of tumors. The tumor tissues were removed from the animals and enzymatic activities were evaluated. The inhibitory effect of tyrosine kinase was found to be enhanced from 36.4% to 68.4% when IMA was used in combination with dexketoprofen trometamol. Furthermore, all dried NPs were found to be stable for more than a year at 25°C. Presented results show that these developed combinatorial drug–loaded NPs can be used for the treatment of fibrosarcoma, and these data can provide an insight, new strategies for productions or alternatives in cancer treatment.     

Intravenous dexmedetomidine for treatment of intraoperative penile erection

Background  

Intraoperative penile erections following the initiation of either regional or general anaesthesia is rare; however, when it occurs in patients undergoing urologic procedures it may delay, or even cancel the planned surgery. The aetiology is unclear. Various treatments proposed for producing detumescence are not always effective. Use of intracavernous alpha-adrenergic agonists is an efficient and rapid but short-lasting treatment. Furthermore, repeated intracavernous injections of vasoactive drugs may be harmful. Dexmedetomidine is a potent, selective α₂-adrenoreceptor agonist. In our study, we evaluated the effect of dexmedetomidine on intraoperative penile erection.     

FcγRIIIa-V/F 158 polymorphism in Turkish children with asthma bronchiale and allergic rhinitis

Fc receptors (FcR) play an important role in immune regulation. This might be linked to the variability in immune response, therefore relating to the pathogenesis of atopic diseases. The aim of the present study was to evaluate the Fc γ RIIIa gene polymorphism in Turkish children with asthma and allergic rhinitis. The study included 364 atopic children (184 bronchial asthma, 180 allergic rhinitis) and 234 healthy subjects as the control group, aged between 5 to 16 years. Patients were recruited from outpatient clinics of allergy and general pediatric care. Plasma IgE concentrations were measured by immunoassays and skin prick test was done in children with atopic diseases. The Fc γ RIIIa gene polymorphism was determined using the polymerase chain reaction method. Distribution of V158V genotype was significantly different among patient groups compared to controls (for asthmatic children OR: 5.33, 95% CI: 2.80–10.23, p < 0.001; for allergic rhinitis OR: 3.25, 95% CI: 1.75–6.07, p = 0.001). Distribution of 158 V allele was significantly different among asthmatic children (OR: 2.20, 95% CI: 1.65–2.92, p < 0.001) and allergic rhinitis patients (OR: 1.77, 95% CI: 1.32–2.35, p < 0.001) compared to healthy controls. Our study shows that the V158V genotype in Fc γ RIIIa gene polymorphism may be a genetic risk factor for the development of atopic diseases.