Early Renal Injury Induced by Caffeine Consumption in Obese,Diabetic ZSF1 Rats

Our previous studies indicate that prolonged caffeine consumption exacerbates renal failure in nephropathy associated with the metabolic syndrome. Reduced activity of the antioxidant defense system and beneficial effects of antioxidant therapy have been reported in diabetic rats and humans. The purpose of this study was to examine the early renal effects of caffeine consumption and the effects of concomitant antioxidant therapy in young obese, diabetic ZSF1 rats. Eleven-week-old male ZSF1 rats were randomized to drink tap water, caffeine (0.1%), tempol (1 mmol/L), or a solution containing caffeine and tempol for nine weeks. Caffeine significantly reduced body weight and glycosuria (weeks 2–9), improved glucose tolerance (week 9), had no effect on elevated plasma triglycerides, plasma cholesterol (week 9) and blood pressure (week 9), and significantly increased plasma cholesterol level (weeks 5 and 9). Yet, as early as after two weeks, caffeine greatly augmented proteinuria and increased renal vascular resistance (RVR) and heart rate (HR: week 9). Tempol had no effects on metabolic status and development of proteinuria, did not alter caffeine-induced metabolic changes and early proteinuria, and attenuated caffeine-induced increase in HR and RVR. Immunohistochemical analysis revealed significant glomerular and interstitial inflammation, proliferation, and fibrosis in control animals. Caffeine augmented the influx of glomerular and interstitial macrophages (ED1+ cells) influx, glomerular and tubular proliferative response, and glomerular collagen IV content. Tempol abolished the exacerbation of renal inflammation, proliferation, and fibrosis induced by caffeine. In conclusion, in nephropathy associated with the metabolic syndrome, caffeine—most likely through the interaction with adenosine receptors and interference with anti-inflammatory and/or glomerular hemodynamic effects of adenosine—augments proteinuria and stimulates some of the key proliferative mechanisms involved in glomerular remodeling and sclerosis. Tempol does not prevent early renal injury (i.e., proteinuria) induced by caffeine, yet abolishes late renal inflammatory, proliferative, and fibrotic change induced by chronic caffeine consumption in obese ZSF1 rats.     

Gender Differences in the Heritability of Musculoskeletal and Body Composition Parameters in Mother-Daughter and Mother-Son Pairs

Bone mass and body composition traits are genetically programmed, but the timing and gender and site specificities of their heritability are unclear. Mother-child correlations of bone mineral density (BMD) and bone mineral content, lean mass, and fat mass were studied in 169 premenopausal mothers and their 239 children. Heritability estimates of lean mass, fat mass, BMD, and area were derived for each gender and pubertal stage. There were significant correlations for most densitometry-derived variables at the spine, hip, femoral neck (FN), and total body (r = 0.192–0.388) in mother-postmenarcheal daughter pairs, for bone areas at all sites in early puberty (r = 0.229–0.508) and for volumetric-derived density at FN and spine (r = 0.238–0.368) in mother-son pairs. Fat mass correlations were significant in both genders after puberty (r = 0.299–0.324) and lean mass in postmenarcheal girls only (r = 0.299). Heritability estimates varied between 21% and 37% for mother-daughter and 18% and 35% for mother-son pairs for density-derived variables and between 26% and 40% for body composition variables. Maternal inheritance of bone traits is expressed in early-pubertal boys for several skeletal site traits but consistently involves most site traits in girls and boys by late puberty. Body composition inheritance is more variable.     

Construct and discriminant validity and dimensionality of the Interview Schedule for Social Interaction (ISSI) in three psychiatric samples

This study was aimed at investigating the psychometric properties of the Interview Schedule for Social Interaction (ISSI), in terms of construct and discriminant validity and unidimensionality, in three psychiatric samples with varying prerequisites for social interaction: 1) an outpatient sample of working age with mixed diagnoses, 2) an outpatient sample with schizophrenia, and 3) an inpatient sample composed of mentally ill, male offenders. The target constructs were psychosocial functioning and satisfaction in different life domains. It was hypothesized that the ISSI would mainly be related to psychosocial functioning and life domains characterized by social interaction, such as friends and family. A second hypothesis was that the ISSI ratings would discriminate between the three samples. The first hypothesis was confirmed, but the pattern of relationships was somewhat different between the groups. Whereas family contacts were of great importance for social integration in Samples 1 and 2, friends seemed more important for the mentally ill offenders. The second hypothesis was partly confirmed: three ISSI sub-scales out of four discriminated between the samples. Moreover, the ISSI proved to be a unidimensional construct. The support for the four proposed sub-scales was not unanimous, however, and the sub-scales targeting attachment constituted less stable factors. This study demonstrated the construct and discriminant validity of the ISSI when applied to samples with various mental disorders. The fact that similar results were obtained in all three samples, despite varying prerequisites for social interaction, strongly supports the validity of the ISSI. Providing the sub-scales are used with caution, the ISSI seems to be a reliable tool for use with patients with severe mental disorders.     

“Tau Protein Targeting Via Radioiodinated Azure A For Brain Theranostics: Radiolabeling,Molecular Docking,in vitro And in vivo Biological Evaluation”

Azure-A is one of the phenothiazines (PTZs) derivatives which for decades have been used as antipsychotic drugs due to good lipophilic characteristics which enable them to pass through the blood brain barrier (BBB), besides the important property of enabeling investigation of the pathological forms of aggregated tau protein found in the neurons of the central nervous system. Radioiodination of Azure-A was carried out via an electrophilic substitution reaction using chloramine-T as oxidizing agent. The influence of various reaction parameters and conditions on radioiodination efficiency was investigated, and a high radiochemical yield of 92.07 ± 0.9 % was obtained. An in vitro cytotoxicity study of iodinated Azure-A on three cell lines (HCT-116, human colon carcinoma cell line; Hep-G2, liver carcinoma cell line and HFB-4, normal human melanocytes) was carried out, and the data revealed that ioiodinated Azure A has no to very low toxic effect. The in vivo biodistribution study of ¹³¹I-Azure A showed a high brain uptake of 6.15 ± 0.09 % injected dose/g tissue organ at 30 minutes post-injection, and its retention in brain remained high up to 2 hours, whereas the clearance from the body appeared to proceed via the renal system. The experimental data were confirmed by the molecular docking studies to predict the effect of radioiodination on the binding affinity of the parent molecule (Azure A) to tau paired helical filaments (PHFs). Both ligands showed better binding to S2 and S3 pockets of (PHFs). Consequently, radioiodinated Azure A seems to be a good candidate as an imaging agent for taupathies such as Alzheimer's disease, chronic traumatic encephalopathy, and corticobasal degeneration. Furthermore, it could be a very potent theranostics agent for brain tumors.     

Contagion of Temporal Discounting Value Preferences in Neurotypical and Autistic Adults

Journal of Autism and Developmental Disorders - Neuroeconomics paradigms have demonstrated that learning about another’s beliefs can make you more like them (i.e., contagion). Due to social...