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

SKELETAL MUSCLE: ONE OF THE SILENT TARGETS OF DIABETIC COMPLICATIONS

ABSTRACTObjective: Muscle weakness in diabetes has been considered a rare manifestation associated with severe diabetic neuropathy. However, similarfindings are lacking in individuals with early diabetes. Handgrip strength is a reliable measurement of the disability index. The present study wasdesigned to determine the effect of early Type 2 diabetes on handgrip strength in adults by handgrip dynamometer.Methods: 30 subjects with diabetes (1-5 years duration) were taken as case, and thirty age and sex-matched subjects without diabetes were takenas controls. Subjects with hypertension, heart diseases, and neuromuscular disorders were excluded. Skeletal muscle function was determined usinghand grip dynamometer. Maximum voluntary contraction (MVC) was measured thrice and best of that it was taken. For endurance time (ET) 50% ofMVC was taken. Anthropometric measurements were taken, and random blood sugar testing was done.Results: Compared to controls, cases had decreased mid forearm circumference (23.97±1.7 cm vs. 23.8±2.7 cm, p<0.005). MVC and ET were alsosignificantly reduced in cases when compared with control subjects (MVC, 32.46±6.865 kg vs. 22.48±4.420 kg, p<0.025) and ET (44.57±17.294 secondsvs. 16.63±9.810 seconds, p<0.022).Conclusion: Our study suggests that there is a decline in skeletal muscle strength in type 2 diabetes even before the disease manifests severely.This provides evidence that impaired grip strength is associated with adverse metabolic profile, in addition, to the loss of physical function, and thepotential for grip strength to be used in the clinical setting needs to be explored.Keywords: Skeletal muscle function, Handgrip, Diabetes, Endurance time, Maximum voluntary contraction

EVALUATION OF PREHYPERTENSION, HYPERTENSION AND ITS ASSOCIATED FACTORS AMONG I YEAR MEDICAL STUDENTS

  Background and Objectives: Pre-hypertension is associated with increased progression to hypertension and cardiovascular risk. The objective of this study is to evaluate the prevalence of pre-hypertension and hypertension, as well as the associated factors among Ist year medical students who are from a similar socioeconomic status, dietary habits and lifestyle.Materials and Methods: This was a cross-sectional study conducted among 137 Ist year medical students using digital blood pressure (BP) monitor on three different occasions and the average was taken and also a questionnaire was obtained to assess the associated factors and other demographic details. Data were analyzed with the use of SPSS software and results were demonstrated using descriptive tables where Chi-square test and one-way analysis was used.Result: The prevalence of elevated BP (pre-hypertension and hypertension) as per JNC 7 criteria, among the medical students was 46.7%. There was a significant association of pre-hypertension with the individual risk factor like the family history of diabetes mellitus, diet and stress.Conclusion: The study shows a significant proportion of individuals with elevated BP at a younger age, associated with risk factors such as family history of diabetes, diet and stress. Elevated BP increases the risk for the development of hypertension during adolescence. Hypertension being a disease of iceberg goes unnoticed leading to chronic disease, therefore identification at the earliest can curb the disease.Keywords: Pre-hypertension, Adolescents, Prevalence, Hypertension

MIGRAINE: A POSSIBLE CAUSE FOR COGNITIVE DECLINE

Objectives:Migraine is the second most common type of headache and seventh most disabling disease worldwide. In general, obesity is often related to headache disorders in several clinical and epidemiologic studies. Obese migraine patients may have an increased attack frequency due to increase in inflammatory response. Cognitive decline is the major pitfall of migraine disorder and there exists a conflicting result between cognition and migraine and the effect of Body Mass Index (BMI) on migraine. So this study is done to find out the relationship between cognition and migraine and its association with BMI.Methods:The study protocol was approved by the ethical committee of SRM Medical College Hospital & Research Centre. The study group consisted of 30 migraine patients and 30 healthy controls aged between 18-40 years of age. Informed consent was obtained from all the participants. Diagnosis of migraine was made using the criteria of 2nd edition of International Headache Classification (IHC). Patients affected by Diabetes mellitus, Hypertension, allergy, inflammation, infection or immune disorders were excluded. Height and weight of the subjects were taken to calculate the BMI. Cognitive tests such as stroop interference trial & trial making tests (A&B) were done to evaluate working memory, mental flexibility and attention.Results:Compared to controls, cases took more time for performing stroop colour card test (106.40 ± 15.87 seconds vs. 132.17±7.027seconds, p<0.001) and trial making pattern B (54.77± 8.169 seconds vs. 56.23 ± 23.457seconds, p=0.004). Among the migraine subjects, obese individuals had an increased frequency of migraine attack per month (Correlation coefficient r=0.797)Conclusion:Cognitive decline in migraine is one of the underestimated problems in migraine. Identifying such problems early can prevent major consequences in day to day activities of migraine patients. Since there is an increased frequency of migraine with increase in BMI, obese migraine subjects can be recommended to do regular exercises.Â

Analysis of BAC-end sequences (BESs) and development of BES-SSR markers for genetic mapping and hybrid purity assessment in pigeonpea (Cajanus spp.)

<p>Abstract</p> <p>Background</p> <p>Pigeonpea [<it>Cajanus cajan </it>(L.) Millsp.] is an important legume crop of rainfed agriculture. Despite of concerted research efforts directed to pigeonpea improvement, stagnated productivity of pigeonpea during last several decades may be accounted to prevalence of various biotic and abiotic constraints and the situation is exacerbated by availability of inadequate genomic resources to undertake any molecular breeding programme for accelerated crop improvement. With the objective of enhancing genomic resources for pigeonpea, this study reports for the first time, large scale development of SSR markers from BAC-end sequences and their subsequent use for genetic mapping and hybridity testing in pigeonpea.</p> <p>Results</p> <p>A set of 88,860 BAC (bacterial artificial chromosome)-end sequences (BESs) were generated after constructing two BAC libraries by using <it>Hin</it>dIII (34,560 clones) and <it>Bam</it>HI (34,560 clones) restriction enzymes. Clustering based on sequence identity of BESs yielded a set of >52K non-redundant sequences, comprising 35 Mbp or >4% of the pigeonpea genome. These sequences were analyzed to develop annotation lists and subdivide the BESs into genome fractions (e.g., genes, retroelements, transpons and non-annotated sequences). Parallel analysis of BESs for microsatellites or simple sequence repeats (SSRs) identified 18,149 SSRs, from which a set of 6,212 SSRs were selected for further analysis. A total of 3,072 novel SSR primer pairs were synthesized and tested for length polymorphism on a set of 22 parental genotypes of 13 mapping populations segregating for traits of interest. In total, we identified 842 polymorphic SSR markers that will have utility in pigeonpea improvement. Based on these markers, the <it>first </it>SSR-based genetic map comprising of 239 loci was developed for this previously uncharacterized genome. Utility of developed SSR markers was also demonstrated by identifying a set of 42 markers each for two hybrids (ICPH 2671 and ICPH 2438) for genetic purity assessment in commercial hybrid breeding programme.</p> <p>Conclusion</p> <p>In summary, while BAC libraries and BESs should be useful for genomics studies, BES-SSR markers, and the genetic map should be very useful for linking the genetic map with a future physical map as well as for molecular breeding in pigeonpea.</p