Oxidative Stress Responses to Nigella sativa Oil Concurrent with a Low‐Calorie Diet in Obese Women: A Randomized,Double‐Blind Controlled Clinical Trial

The aim of the present study was to determine the effects of Nigella sativa (NS) oil concurrent with a low‐calorie diet on lipid peroxidation and oxidative status in obese women. In this double‐blind placebo‐controlled randomized clinical trial, 50 volunteer obese (body mass index = 30–35 kg/m²) women aged 25–50 years old were recruited. Participants were randomly divided into intervention (n = 25) and placebo (n = 25) groups. They received a low‐calorie diet with 3 g/day NS oil or low‐calorie diet with 3 g/day placebo for 8 weeks. Forty‐nine women (intervention group = 25; placebo group = 24) completed the trial. NS oil concurrent with a low‐calorie diet decreased weight in the NS group compared to the placebo group (?4.80 ± 1.50 vs. ?1.40 ± 1.90 kg; p < 0.01). Comparison of red blood cell superoxidase dismutase (SOD) indicated significant changes in the NS group compared to the placebo group at the end of the study (88.98 ± 87.46 vs. ?3.30 ± 109.80 U/gHb; p < 0.01). But no significant changes in lipid peroxidation, glutathione peroxidase, and total antioxidant capacity concentrations were observed. NS oil concurrent with a low‐calorie diet decreased weight and increased SOD levels in obese women. However, more studies are suggested to confirm the positive effects of NS in obesity and its complications. Copyright © 2015 John Wiley & Sons, Ltd.     

Predictors of non-alcoholic fatty liver in a group of non-obese and non-diabetic Iranian adults

Non-alcoholic fatty liver disease (NAFLD) is not uncommon in non-obese people. We examined the independent predictors of NAFLD in a group of non-obese and non-diabetic men and women in Rasht, Iran. Sixty-one adults aged 38.4 ± 8.4 years (32 men and 29 women) with body mass index (BMI) <30 kg/m² and non-diabetic with clinical features of NAFLD who visited our center between 2007 and 2009 were compared to 147 non-obese, non-diabetic and normal liver subjects (40 men and 107 women) aged 40.8 ± 9.1. Data on blood lipids, anthropometry, fasting blood glucose, exercise, and educational levels were gathered using a questionnaire. Logistic regression analysis revealed that weight gain during adulthood [OR = 1.90 (95% CI = 1.03–1.84), P < 0.04] and high serum triglyceride levels [OR = 1.19 (95% CI = 1.09–1.28), P < 0.0001] were independent predictors of NAFLD in this group of non-obese subjects. BMI, educational levels, gender, and habitual physical activity were not independently related to NAFLD in this study. These data suggest that weight gain after 20 years of age rather than BMI and high levels of triglyceride may serve as screening tool for NAFLD in clinical practice in this population. In nutritional management of these apparently normal weight subjects with NAFLD modest weight loss is necessary.     

Global CNS Transduction of Adult Mice by Intravenously Delivered rAAVrh.8 and rAAVrh.10 and Nonhuman Primates by rAAVrh.10

Some recombinant adeno-associated viruses (rAAVs) can cross the neonatal blood–brain barrier (BBB) and efficiently transduce cells of the central nervous system (CNS). However, in the adult CNS, transduction levels by systemically delivered rAAVs are significantly reduced, limiting their potential for CNS gene therapy. Here, we characterized 12 different rAAVEGFPs in the adult mouse CNS following intravenous delivery. We show that the capability of crossing the adult BBB and achieving widespread CNS transduction is a common character of AAV serotypes tested. Of note, rAAVrh.8 is the leading vector for robust global transduction of glial and neuronal cell types in regions of clinical importance such as cortex, caudate-putamen, hippocampus, corpus callosum, and substantia nigra. It also displays reduced peripheral tissue tropism compared to other leading vectors. Additionally, we evaluated rAAVrh.10 with and without microRNA (miRNA)-regulated expressional detargeting from peripheral tissues for systemic gene delivery to the CNS in marmosets. Our results indicate that rAAVrh.8, along with rh.10 and 9, hold the best promise for developing novel therapeutic strategies to treat neurological diseases in the adult patient population. Additionally, systemically delivered rAAVrh.10 can transduce the CNS efficiently, and its transgene expression can be limited in the periphery by endogenous miRNAs in adult marmosets.     

Cytotoxic effects of SMAC-mimetic compound LCL161 in head and neck cancer cell lines

Objectives

Head and neck squamous cell carcinoma (HNSCC) is one of the most common tumor entities worldwide. Unfortunately, recent drug developments in other fields of oncology have yielded no efficacy in the treatment of oral squamous cell carcinoma. As a new starting point, we investigated the impact of Fas ligand (FasL) and the SMAC-mimetic compound LCL161 in mono- and combination treatment in HNSCC cell lines.

Methods

Five different cell lines of HNSCC were treated with FasL and LCL161 in mono- and combination treatment. Cytotoxicity was measured via a crystal violet assay. The cell lines were characterized for CD95 (FasL receptor) expression via flow cytometry. The degradation of cellular inhibitor of apoptosis protein 1 (cIAP1) was detected via Western blot.

Results

Incubation with FasL led to a significant decrease in three out of five cell lines. Combination treatment with LCL161 enhanced cytotoxicity significantly. Two cell lines were FasL resistant, but one of them could be resensitized with LCL161. In all cell lines, Western blot analysis showed degradation of cIAP1 after LCL161 application. However, one cell line showed only minor vulnerability to the FasL and LCL161 combination.

Conclusion

This is the first study investigating combination treatment of FasL and LCL161 in head and neck cancer cell lines. Pro-apoptotic effects of the combination were detected in the majority of the cell lines. Interestingly, one of two FasL-resistant cell lines was sensitive to the combination therapy with FasL and LCL161.

Clinical relevance

SMAC-mimetic compounds show promising results in the treatment of other tumor entities in vitro and might be useful drugs to improve HNSCC therapy.

     

Sudden Unilateral Vision Loss Arising from Calcified Amorphous Tumor of the Left Ventricle

Calcified amorphous tumor of the heart is a very rare non-neoplastic intracavitary mass. The clinical presentation is similar to that of other cardiac masses. The precise cause and best approach to treatment remain unclear. We describe a case of cardiac calcified amorphous tumor presenting with refractory unilateral vision loss that was successfully treated by surgical excision. To our knowledge, this is only the 2nd reported case of retinal arterial embolism due to cardiac calcified amorphous tumor in the English-language literature.Key words: Blindness/etiology, calcinosis/complications/radiography/surgery, diagnosis, differential, tumor, cardiac calcified amorphous, vision loss, suddenCalcified amorphous tumor (CAT) of the heart is a very rare non-neoplastic cardiac intracavitary mass. It was first described as a distinct pathologic entity by Reynolds and colleagues in 1997.¹ Since then, very few cases of cardiac CAT have been reported in the English-language medical literature^2–19 (12 TABLE I. Clinicopathologic Findings of Published Cases of Cardiac Calcified Amorphous Tumor Open in a separate window TABLE I, continued. Clinicopathologic Findings of Published Cases of Cardiac Calcified Amorphous Tumor Open in a separate window In the present report, we describe a case in which cardiac CAT presented with refractory unilateral vision loss, which was successfully treated by surgical excision.     

Dysbaric osteonecrosis in diving fisherman: a case report

Background:Dysbaric osteonecrosis (DON) is defined as avascular bone necrosis, usually involving specific parts of the long bones, which is seen in divers or compressed-air workers due to exposure to pressure. We describe a case of DON in an artisanal diving fisherman working underwater for many years.Methods:A 48-year-old male case was admitted to the occupational disease outpatient with left shoulder and arm pain for 1-2 years. Since the age of 20, he has been artisanal diving fishing with a hookah at a depth of 20-25 meters in the sea. In 2011, he received hyperbaric oxygen therapy for widespread pain in the whole body due to decompression sickness (DCS). In the case’s left shoulder joint x-ray and magnetic resonance imaging, degenerative changes in the acromioclavicular joint and signal changes consistent with osteonecrosis starting from the subcortical area of the humeral head and extending to the proximal shaft of the humerus were observed.Conclusions:DON is among the most common long-term pathologies in professional divers. In Turkey, as in our case, not applying safe decompression procedures and unsafe diving practices are common among diving fishers. In studies, the frequency of exposure to pressure, duration and depth of dive, insufficient decompression, formation of DCS and increasing age were associated with DON. Today, DON remains an occupational hazard with significant medical and social consequences. Diving fishers should be informed about the sequelae of DCS and trained on the safety measures to be taken.