PHOSPHORYLATION OF TAU PROTEIN IN BRAIN REGIONS OF CHRONIC RENAL FAILURE - INDUCED RATS: AMELIORATIVE EFFECT OF ERYTHROPOIETIN

Objectives: Chronic kidney disease (CKD) is a major clinical health problem as it is a systemic disorder that causes widespread organ damageand it is related to significant morbidity and mortality. Numerous studies have shown that, cognitive dysfunction increase in prevalence, due toincrease in reactive oxygen species in CKD severity. Tau proteins are proteins that stabilize microtubules. Hyperphosphorylation of tau reduces itsability to bind to microtubule causes dystabilization and production of neurofibrillary tangles (NFT) and neurodegeneration in the brain. Aberranthyperphosphorylation of tau is critical to the progression of neurodegeneration. Erythropoietin (EPO), a glycoprotein has been in clinical use formillions of anemic patients, and some studies show it has a neuroprotective role. Till now studies on the level of tau protein phosphorylation in brainregions of CKD-induced experimental animals and impact of EPO therapy are scarce. The aim of this study is to determine the impact of CKD and EPOtherapy on tau protein phosphorylation in brain regions of experimental rats.Methods: This study was performed on 48 adult male Wistar rats. Two phases were conducted to find out the difference between simultaneous andposttreatment of EPO. Phase I: 24 adult male Wistar rats were divided into 4 groups (6 animals each): Group 1: Control, Group 2: 0.75% of adeninemixed diet for 4 weeks, Group 3: 0.75% of adenine mixed diet was given for 4 weeks and simultaneous administration of EPO (100 IU/kg btw, ip)thrice weekly. Group 4: EPO alone (100 IU/Kg btw, ip) thrice per week. All the animals were sacrificed uniformly at the end of 4 weeks. In Phase II,24 animals were maintained separately for 40 days experimental period and divided into 4 groups. Groups 1, 2, and 4 animals were treated as samementioned in Phase I. Group 3: For EPO posttreatment, adenine mixed diet was given for 4 weeks for chronic renal failure (CRF) induction. After the 4week, EPO (100 IU/Kg btw.) was administered daily once for 12 days. At the end of the 40 days, all the animals were sacrificed uniformly. In both thephases after the treatment period, the brain tissue was removed and samples were homogenized. Total tau protein and phosphorylated tau proteinexpressions were analyzed by western blotting method.Results: In results, both the total tau and phosphorylated tau protein levels were significantly increased all the brain regions of CRF-induced groupswhen compared to control. In both simultaneous and posttreatment of EPO, the levels were retrieved.Conclusion: This study proves that EPO supplementation has a promising role in neuroprotection by preventing abnormal phosphorylated tauprotein accumulation. This study also proves the clinical usefulness of EPO as a supplemental therapeutic agent in neurotoxicity.Keywords: Chronic renal failure, Cognitive dysfunction, Hyperphosphorylation of tau protein, Erythropoietin.t

Role of P-selectin in platelet sequestration in pulmonary capillaries during endotoxemia

Background: There is growing evidence that platelets accumulate in the lung and contribute to the pathogenesis of acute lung injury during endotoxemia. The aims of the present study were to localize platelet sequestration in the pulmonary microcirculation and to investigate the role of P-selectin as a molecular mechanism of platelet endothelial cell interaction. Methods: We used in vivo fluorescence microscopy to quantify the kinetics of fluorescently labeled erythrocytes and platelets in alveolar capillary networks in rabbit lungs. Results: Six hours after onset of endotoxin infusion we observed a massive rolling along and firm adherence of platelets to lung capillary endothelial cells whereas under control conditions no platelet sequestration was detected. P-selectin was expressed on the surface of separated platelets which were incubated with endotoxin and in lung tissue. Pretreatment of platelets with fucoidin, a P-selectin antagonist, significantly attenuated the endotoxin-induced platelet rolling and adherence. In contrast, intravenous infusion of fucoidin in endotoxin-treated rabbits did not inhibit platelet sequestration in pulmonary capillaries. Conclusion: We conclude that platelets accumulate in alveolar capillaries following endotoxemia. P-selectin expressed on the surface of platelets seems to play an important role in mediating this platelet-endothelial cell interaction. Copyright (c) 2006 S. Karger AG, Basel

"They're Really PD Today": An Exploration of Mental Health Nursing Students' Perceptions of Developing a Therapeutic Relationship With Patients With a Diagnosis of Antisocial Personality Disorder

The therapeutic relationship is of particular importance when working with patients with antisocial personality disorder, but despite this, there is a paucity of literature exploring student nurses’ perceptions of developing a therapeutic relationship with such patients. Hence, this qualitative study explored the perceptions of second-year mental health nursing students of developing a therapeutic relationship with this patient group. Student nurses from a University in the Northwest of England participated in two focus groups, to compare the perceptions of a group of student nurses who had experience in secure settings (forensic hospital) with those who had not. Four key themes emerged: diagnosis, safety, engagement, and finally environmental influences. Both groups commented on looking beyond the diagnosis and seeing the person. The student nurses cited other staff in their clinical placement areas as hugely influential in terms of the development of their perceptions of patients with antisocial personality disorder and how to relate to them

The differential contribution of maternal and paternal values to social competence of preschoolers

Multivariate analyses were conducted to clarify the nature of the influences of parental values on social behaviours of kindergarteners in the context of sociodemographic variables and sex of participants. This study included 217 mothers and 172 fathers from the same families, who completed a socio-demographic questionnaire and a new Q-sort that assesses parental values on Individualism (IND)/Collectivism (COL) and Horizontal (HOR)/Vertical (VER) continuums.To test the hypothesis of an association between parental values and children’s behaviours, teachers also provided information about each child’s social competence, anger-aggression, and anxiety-withdrawal in kindergarten using the Social Competence and Behavior Scale. Parents shared a greater proportion of IND/COL than VER values and mothers were more likely to emphasise IND and COL values than fathers. Mothers within IND and COL groups had more socially competent kindergartners as reported by teachers. Considering the mixed results found in the literature regarding sex differences in parenting and behaviours of children, the present results suggested that examining more closely the system of parental values might offer valuable avenues for uture research on early childhood socialisation

Political activism across the life course

The study of political activism has neglected people’s personal and social relationships to time. Age, life course and generation have become increasing important experiences for understanding political participation and political outcomes (e.g. Brexit), and current policies of austerity across the world are affecting people of all ages. At a time when social science is struggling to understand the rapid and unexpected changes to the current political landscape, the essay argues that the study of political activism can be enriched by engaging with the temporal dimensions of people’s everyday social experiences because it enables the discovery of political activism in mundane activities as well as in banal spaces. The authors suggest that a values-based approach that focuses on people’s relationships of concern would be a suitable way to surface contemporary political sites and experiences of activism across the life course and for different generations

Isolation and Characterization of Bacteria from the Gut of Bombyx mori that Degrade Cellulose, Xylan, Pectin and Starch and Their Impact on Digestion

Bombyx mori L. (Lepidoptera: Bombycidae) have been domesticated and widely used for silk production. It feeds on mulberry leaves. Mulberry leaves are mainly composed of pectin, xylan, cellulose and starch. Some of the digestive enzymes that degrade these carbohydrates might be produced by gut bacteria. Eleven isolates were obtained from the digestive tract of B. mori, including the Gram positive Bacillus circulans and Gram negative Proteus vulgaris, Klebsiella pneumoniae, Escherichia coli, Citrobacter freundii, Serratia liquefaciens, Enterobacter sp., Pseudomonas fluorescens, P. aeruginosa, Aeromonas sp., and Erwinia sp.. Three of these isolates, P. vulgaris, K. pneumoniae, C. freundii, were cellulolytic and xylanolytic, P. fluorescens and Erwinia sp., were pectinolytic and K. pneumoniae degraded starch. Aeromonas sp. was able to utilize the CMcellulose and xylan. S. liquefaciens was able to utilize three polysaccharides including CMcellulose, xylan and pectin. B. circulans was able to utilize all four polysaccharides with different efficacy. The gut of B. mori has an alkaline pH and all of the isolated bacterial strains were found to grow and degrade polysaccharides at alkaline pH. The number of cellulolytic bacteria increases with each instar

Family Income Gradients in the Health and Health Care Access of US Children

This study sought to examine the shape and magnitude of family income gradients in US children’s health, access to care, and use of services. We analyzed cross-sectional data from the 2003 National Survey of Children’s Health, a telephone survey of 102,353 parents of children aged 0–17 years. Associations between family income [Below 100% Federal Poverty Level (FPL), 100–199% FPL, 200–299% FPL, 300–399% FPL, 400% FPL or Greater] and a set of 32 health and health care indicators were examined using linear polynomial testing and multivariate logistic regression. The percentage of children in better health increased with family income for 15 health outcomes. In multivariate logistic regression models that controlled for health insurance coverage and socio-demographic confounders, odds ratios >2 comparing the lowest to the highest income groups were noted for health conditions across both physical and developmental domains (diabetes, headaches, ear infections, learning disabilities, behavior/conduct problems, speech problems). Parent-reported global child health status, activity limitation, and oral health status showed steeper gradients than specific chronic and acute conditions. Ten measures of health care access and utilization were associated with family income in multivariate logistic regression models. Income gradients are pervasive across many health indicators at an early age. Social and health policy interventions are needed to address the multitude of factors that can affect children’s health and initiate disparities in development

A model of hypertension and proteinuria in cancer patients treated with the anti-angiogenic drug E7080

Hypertension and proteinuria are commonly observed side-effects for anti-angiogenic drugs targeting the VEGF pathway. In most cases, hypertension can be controlled by prescription of anti-hypertensive (AH) therapy, while proteinuria often requires dose reductions or dose delays. We aimed to construct a pharmacokinetic–pharmacodynamic (PK–PD) model for hypertension and proteinuria following treatment with the experimental VEGF-inhibitor E7080, which would allow optimization of treatment, by assessing the influence of anti-hypertensive medication and dose reduction or dose delays in treating and avoiding toxicity. Data was collected from a phase I study of E7080 (n = 67), an inhibitor of multiple tyrosine kinases, among which VEGF. Blood pressure and urinalysis data were recorded weekly. Modeling was performed in NONMEM, and direct and indirect response PK–PD models were evaluated. A previously developed PK model was used. An indirect response PK–PD model described the increase in BP best, while the probability of developing proteinuria toxicity in response to exposure to E7080, was best described by a Markov transition model. This model may guide clinical interventions and provide treatment recommendations for E7080, and may serve as a template model for other drugs in this class