A Role for the Potassium Channel Seizure in Regulating Intrinsic Neuronal Stress Response in Drosophila melanogaster

From the Washington University Senior Honors Thesis Abstracts (WUSHTA), Spring 2018. Published by the Office of Undergraduate Research. Joy Zalis Kiefer, Director of Undergraduate Research and Associate Dean in the College of Arts & Sciences; Lindsey Paunovich, Editor; Helen Human, Programs Manager and Assistant Dean in the College of Arts and Sciences Mentor: Yehuda Ben-Shahar and Alexis Hil

A REVIEW ON TREATMENT AND PREVENTION OF DIABETES MELLITUS

Diabetes mellitus is an endocrinological and metabolic disorder with an increasing global prevalence and incidence. High blood glucose levels are symptomatic of diabetes mellitus as a consequence of inadequate pancreatic insulin secretion or poor insulin-directed mobilization of glucose by target cells. Diabetes mellitus is aggravated by and associated with metabolic complications that can subsequently lead to premature death. The diagnosis of diabetes in an asymptomatic subject should never be made on the basis of a single abnormal blood glucose value. For the asymptomatic person, at least one additional plasma/blood glucose test result with a value in the diabetic range is essential, either fasting, from a random (casual) sample, or from the oral glucose tolerance test (OGTT). If such samples fail to confirm the diagnosis of diabetes mellitus, it will usually be advisable to maintain surveillance with periodic re–testing until the diagnostic situation becomes clear. In these circumstances, the clinician should take into consideration such additional factors as ethnicity, family history, age, adiposity, and concomitant disorders, before deciding on a diagnostic or therapeutic course of action. An alternative to blood glucose estimation or the OGTT has long been sought to simplify the diagnosis of diabetes. Diabetes is a metabolic disorder that can be prevented through lifestyle modification, diet control, and control of overweight and obesity. Education of the populace is still key to the control of this emerging epidemic. Novel drugs are being developed, yet no cure is available in sight for the disease, despite new insight into the pathophysiology of the disease

SYNTHESIS AND CHARACTERIZATION OF AZO CONJUGATES OF FENOPROFEN FOR TREATMENT OF INFLAMMATORY BOWEL DISEASE THROUGH COLON TARGETING

Objective: The objective of this research was to synthesize azo conjugates of fenoprofen (FP) for treatment of inflammatory bowel disease through colon targeting. Methods: Six prodrugs of FP were synthesized by diazotisation with ethyl esters of amino acids, namely, glycine, tyrosine L-phenylalanine, L-tryptophan, L-valine, L-alanine, amino acid. Methyl ester hydrochloride prepared by thionyl chloride, methanol and amino acids, followed by diazotization and then Coupling of diazotized amino acid methyl ester with fenoprofen. Six azo prodrug of fenoprofen was synthesized by using amino acid. Further, the synthesized prodrugs were characterized by TLC, IR, NMR spectroscopic analysis and subjected to in vitro drug release, TNBS induced ulcerative colitis and ulcerogenic index. Results: All synthesized prodrugs showed excellent pharmacological response and targeting to colon. The FTIR and NMR study confirmed the structure of all azo linkage prodrugs. In vitro drug release studies revealed that FP was not release in gastric fluid. 12-15% drug were released in intestinal fluid and 65-85% drug was released in the colon because of azo reductases enzyme, secreted by colonic microflora. The azo prodrugs proved their potential in reducing the inflammation proved by the histopathology of the resected colon from every group of animals. Conclusion: The results obtained in this research work clearly indicated a promising potential for treatment of inflammatory bowel disease through colon targeting for the effective treatment of IBD

Can routinely collected primary care data determine the prevalence of chronic kidney disease and predict clinical events in patients with stages 3 of the disease?

Introduction Chronic Kidney Disease (CKD) is common and associated with cardiovascular morbidity and mortality. Few studies have assessed the real prevalence of CKD and the predictors of morbidity and mortality in this cohort. Methods Using THIN data, the prevalence of CKD 1-5 was ascertained .This was compared to the prevalence on the practice register using QOF Read codes in 2009. Cox proportional hazard models using routinely collected primary care were used identify predictors of i) all-cause mortality and ii) the composite of cardiovascular disease and all-cause mortality. Results The prevalence of CKD 1-5 was 5.01%. Patients with CKD not on the practice register were associated with worse management than those on the practice register. Increasing age and co-morbidity were associated with worse outcomes. Continuous variables such as hypertension, BMI, haemoglobin and cholesterol were associated with an inverse J shaped relationship with log relative hazard ratio. Antihypertensives and lipid lowering drug usage, and non white ethnicity was associated with improved outcomes. Blood thinning agents and diuretics were associated with worse outcomes. Conclusions CKD is common in UK. Many practices mis-label CKD which impacts upon management. Some predictors of mortality and morbidity is different to previous reports and this requires further investigation

Relationship between cerebral oxygenation, cardiac output, and blood pressure during transitional period in extremely low gestational age neonates

ObjectiveTo describe the relationship between cerebral oxygenation, cardiac output, arterial blood pressure (BP), and cerebral blood flow velocity in extremely low gestational age neonates (ELGANs) during transition.MethodsThis study comprises secondary analyses from a prospective observational study conducted at a tertiary Neonatal Intensive Care Unit. Recruited ELGANs underwent cerebral saturation (CrSO2) monitoring and serial echocardiography during 72 h from birth. Correlative analyses of CrSO2 and cerebral fractional tissue oxygen extraction (CFTOE) with left (LVO) and right ventricular output (RVO), superior vena cava (SVC) flow, middle cerebral artery blood flow mean velocity (MCA.MV), systolic (SBP), diastolic (DBP), and mean (MBP) BP were conducted.ResultsFifty ELGANs with median (range) gestational age of 25.9 (23.1–27.9) weeks were recruited. Echocardiography was performed sequentially at a median (range) age 5.0 (3.8–6.6), 17.3 (15.4–19.4), 31.0 (27.0–34.1), and 53.7 (49.3–58.3) hours. RVO, LVO, CrSO2, and SBP increased over time but no changes in MBP, DBP, CFTOE, MCA.MV or SVC flow were noted. A weak correlation was identified between CrSO2 and SBP (r2 = 0.11, p = 0.047) and MBP (r2 = 0.12, p = 0.04) at 17.3 (15.4–19.4) hours. No correlation of either CrSO2 or CFTOE with any measures of blood flow was identified.ConclusionThere is a weak correlation between measures of cardiac output, BP, and MCA.MV with both CrSO2 and CFTOE in ELGANs during transition. Whether this finding suggests intact cerebral autoregulation requires prospective evaluation in a cohort of sick ELGANs

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

The Role of the Potassium Ion Channel Seizure (sei) in Regulating Behavior in Drosphila melanogaster

From the Washington University Undergraduate Research Digest: WUURD, Volume 11, 2015-2016. Published by the Office of Undergraduate Research, Joy Zalis Kiefer Director of Undergraduate Research and Assistant Dean in the College of Arts & Sciences; Lindsey Paunovich, Editor; Kristin Sobotka, Editor; Jennifer Kohl. Mentor: Yehuda Ben-Shaha