Insulin binding substances,autoimmunity and type i diabetes in kuwaiti patients and their kindred

Summary Insulin autoantibodies (IAAs) are associated with type I diabetes mellitus (DM) and have been suggested as predictive markers of the disease. Using an ELISA assay, we have studied the prevalence of binding to human insulin in sera from an Arab type I DM population and compared it with the prevalence in the family members (FMs) of the probands, in type II DM patients from the same population, and in Arab control subjects. Significant levels of binding occurred in 11/16 (69%) of type I DM patients and in 21/34 (62%) of their FMs, but in only 5/31 (16%) of type II DM patients and in 1/25 (4%) of control subjects. Within families, there was homogeneity with regard to the level of insulin binding and the mean family levels correlated with those of the proband (r=0.68, df=7, p=0.05). HLA-DR3 or -DR4 antigens occurred in 55/63 (87%) of type I DM patients and in 95/118 (81%) of their FMs. This was significantly higher (p<0.001) than in either type II DM patients (39/75, 52%) or in control subjects (34/93, 37%). ICAs were present in significantly more (25/43, 58%) of type I DM patients than their FMs (3/82, 3%) (p<0.001). They did not occur in either type II DM patients or in the control group. In conclusion, insulin binding occurred in sera from both type I diabetic patients and their kindred, and hence did not appear to be specifically associated with the development of clinical diabetes.     

Characteristics and management of cleft mitral valve

OBJECTIVES: We sought to highlight the clinical, morphologic, and pathogenetic features in patients with a cleft mitral valve (MV). BACKGROUND: Few studies have addressed the morphologic features of cleft MV and the outcome of these patients. The pathogenetic features, including the developmental relation to an atrioventricular (AV) septal defect, remain unclear. METHODS: We reviewed the patients with cleft MV that were diagnosed by echocardiography since 1980. Patients with an AV canal, ventriculo-arterial discordance, and hypoplastic ventricles were excluded. RESULTS: Twenty-two patients were identified at a median age of 0.5 years (range 0 to 10.6). In three patients, no chordal attachments of the cleft to the ventricular septum were seen. Ten patients had significant mitral regurgitation (MR), and three had subaortic obstruction by the cleft. Associated cardiac lesions and extracardiac features were present in 13 and 10 patients, respectively. During the median follow-up period of 1.5 years (range 0 to 11.8), two patients died of extracardiac causes, and one neonate died of severe subaortic obstruction. Surgical repair was performed in 10 patients at a median age of 5.2 years (range 1.3 to 10.6). Multivariate analysis showed no predictors for MV surgery. One patient was re-operated for mitral stenosis associated with aortic valve stenosis. Follow-up echocardiography demonstrated moderate MR in two unoperated patients and moderate MV stenosis in two operated patients. CONCLUSIONS: A cleft of the MV comprises a wide spectrum. Important morphologic differences exist with an AV septal defect, although the two lesions may be pathogenetically related. Surgical repair always seems possible. Long-term echocardiographic follow-up is warranted.     

Mid-term results of transcatheter closure of ventricular septal defect using Nit-Occlud Lê ventricular septal defect coil,single-center experience

Objectives

To assess safety, efficacy and follow-up results of transcatheter closure of ventricular septal defect (VSD) using Nit-Occlud_ Lê VSD Coil (pfm medical, KÖln, Germany).

Design,synthesis, antimicrobial,and DNA gyrase inhibitory properties of fluoroquinolone–dichloroacetic acid hybrids

A series of new fluoroquinolone conjugates 8a–g and 9a–f were synthesized via benzotriazole‐mediated synthetic approach with good yield and purity. Some of the synthesized analogs exhibited significant antibacterial properties against Escherichia coli and Staphylococcus aureus with potency higher than that of the parent drugs through in vitro standard bioassay procedure (conjugates 8c and 8d reveal antimicrobial properties with potency 1.9, 61.9, 20.7 and 2.4, 37.1, 8.3 folds relative to the parent antibiotic 6 against E. coli, S. aureus, and Enterococcus faecalis, respectively). The observed experimental data were supported by enzymatic DNA gyrase inhibitory property. Developed BMLR‐QSAR model validates the observed experimental data and recognizes the parameters responsible for the enhanced antibacterial properties.     

Effects of free and nanoparticulate curcumin on chemically induced liver carcinoma in an animal model

IntroductionCurcumin therapeutic applications are constrained by its prominent metabolic instability as well as inadequate absorption and bioavailability. The current study was designed to enhance the curcumin bioavailability by exploiting nanoparticles.Material and methodsEleven groups of mice were divided into: normal and nanoparticle control groups, a hepatocellular carcinoma (HCC) group induced by diethylnitrosamine (DEN), 2 groups treated with DEN plus a high dose/low dose of free curcumin, 2 groups treated with a high dose/low dose of free curcumin, 2 groups treated with DEN plus a high dose/low dose of nanoparticulate curcumin, and 2 groups treated with a high dose/low dose of nanoparticulate curcumin.ResultsDEN administration significantly increased liver enzymes, vascular endothelial growth factor, tumor necrosis factor-α, α-fetoprotein, malondialdehyde, and nucelar factor-κB. Also, it decreased serum albumin and tissue antioxidant activities and caused severe histological changes in hepatic tissue. Oral treatment of DEN-injected mice with either a high dose of free curcumin or the tested doses of nanoparticulate curcumin resulted in a significant improvement of all the tested parameters.ConclusionsAlthough the two tested doses of nanoparticulate curcumin were much lower than free curcumin, both doses were effective in preventing HCC development while the low dose of free curcumin was hardly effective. Hence, we conclude that nanoparticles enhance the bioavailability of curcumin.     

Neuroanatomical MRI study: reference values for the measurements of brainstem,cerebellar vermis,and peduncles

Objectives:To set age-specific normal reference values for brainstem, cerebellar vermis, and peduncles measurements and characterize values’ variations according to gender, age, and age by gender interaction.Methods:565 normal brain magnetic resonance examinations with normal anatomy and signal intensity of the supra- and infratentorial structures were categorized into six age groups (infant, child, adolescent, young adult, middle-age adult, and old aged adults). Patients with congenital malformations, gross pathology of the supra- or infratentorial brain, brain volume loss, developmental delay, metabolic disorders, and neuropsychological disorders (n = 2.839) were excluded. On midsagittal T₁ weighted and axial T₂ weighted images specific linear diameters and ratios of the brainstem, cerebellar vermis, and peduncles were attained. Two observers assessed a random sample of 100 subjects to evaluate the inter- and intraobserver reproducibility. Intraclass correlation coefficients, means ± standard deviation, one and two-way analysis of variance tests were used in the statistical analysis.Results:Good to excellent inter- and intraobserver measurements’ reproducibility were observed, except for the transverse diameter of the midbrain, the anteroposterior diameter of the medulla oblongata at the pontomedullary and cervicomedullary junctions, cerebellar vermis anteroposterior diameter, and thickness of the superior cerebellar peduncle. Age-specific mean values of the investigated measurements were established. A significant gender-related variation was recorded in the anteroposterior diameter of the basis pontis (p = 0.044), the anteroposterior diameter of the medulla oblongata at the cervicomedullary junction (p = 0.044), and cerebellar vermis height (p = 0.018). A significant age-related change was detected in all measurements except the tectal ratio. Age by gender interaction had a statistically significant effect on the tectal ratio, inferior, and middle cerebellar peduncles’ thickness (p = 0.001, 0.022, and 0.028, respectively).Conclusion:This study provides age-specific normal mean values for various linear dimensions and ratios of the posterior fossa structures with documentation of measurements’ variability according to gender, age, and their interaction.Advances in knowledge:It provides a valuable reference in the clinical practice for easier differentiation between physiological and pathological conditions of the posterior fossa structures especially various neurodegenerative diseases and congenital anomalies.     

Situating language in a minimal social context: how seeing a picture of the speaker’s face affects language comprehension

Natural use of language involves at least two individuals. Some studies have focused on the interaction between senders in communicative situations and how the knowledge about the speaker can bias language comprehension. However, the mere effect of a face as a social context on language processing remains unknown. In the present study, we used event-related potentials to investigate the semantic and morphosyntactic processing of speech in the presence of a photographic portrait of the speaker. In Experiment 1, we show that the N400, a component related to semantic comprehension, increased its amplitude when processed within this minimal social context compared to a scrambled face control condition. Hence, the semantic neural processing of speech is sensitive to the concomitant perception of a picture of the speaker’s face, even if irrelevant to the content of the sentences. Moreover, a late posterior negativity effect was found to the presentation of the speaker’s face compared to control stimuli. In contrast, in Experiment 2, we found that morphosyntactic processing, as reflected in left anterior negativity and P600 effects, is not notably affected by the presence of the speaker’s portrait. Overall, the present findings suggest that the mere presence of the speaker’s image seems to trigger a minimal communicative context, increasing processing resources for language comprehension at the semantic level.     

Using an UPLC/MS-based untargeted metabolomics approach for assessing the antioxidant capacity and anti-aging potential of selected herbs

Aging is an unavoidable fate that afflicts all life, during this process in mammals reactive oxygen species (ROS) are generated which stimulate tyrosinase, elastase and collagenase activities that actively participate in skin aging. Therefore, the maintenance of antioxidant homeostasis is an important anti-aging strategy for skin. Nature has excellent anti-aging remedies that act externally as well as internally to delay the visual signs of aging. In view of this fact, the present study investigates the in vitro anti-aging activity of five medicinal plants belonging to phenolic rich families namely Rosmarinus officinalis, Lavandula officinalis, Matricaria chamomilla, Camellia sinensis and Pelargonium graveolens. The selected plants are those most frequently used in the preparation of ethnomedicinal recipes for the prevention or treatment of aging. The inhibitory effects of the ethanolic and aqueous extracts of the five selected plants on the activity of tyrosinase, elastase, and collagenase enzymes were investigated. Furthermore, the chemical composition of the plants and the antioxidant capacity of their extracts were assessed. The results showed that R. officinalis had the highest total phenolics content which was correlated with its potent antioxidant and anti-aging activities. To pinpoint the active metabolites in the tested extracts, we evaluated the metabolite variations using ultra-performance liquid chromatography coupled with high resolution electrospray ionization-tandem mass spectrometry (UPLC-HR-ESI-MS/MS). Multivariate data analysis (MVDA) revealed that R. officinalis significantly accumulated metabolites from the aromatic diterpenoid, flavonoid and phenolic acid classes. These results indicate that rosemary can be used for further development of topical preparations with anti-aging properties.

Aging is an unavoidable fate that afflicts all life, during this process in mammals, reactive oxygen species (ROS) are generated which stimulate tyrosinase, elastase and collagenase activities that actively participate in skin aging.