CHRONIC KIDNEY DISEASE AND ITS MANAGEMENT: A REVIEW

Chronic kidney disease (CKD) is a major public health problem worldwide and its prevalence is increasing day by day. CKD defines as kidney damage or a decreased glomerular filtration rate of less than 60 mL/min/1.73 m2 for 3 or more months irrespective of cause. It has deeper effects on morbidity, mortality, health care costs, as well as on patient quality of life and on important social implications. CKD patients have several other co-morbidities such as hypertension, diabetes mellitus, coronary artery disease and anemia , and due to these co morbidities, patients are on multiple medications, and are higher risk of developing drug-related problems. Hypertension is a major promoter of the decline in glomerular filtration rate (GFR) and a strong independent risk factor along with Diabetes mellitus for CKD. Treatment of high blood pressure is recommended for all individuals with, or at risk of, chronic kidney disease. Glycemic control can help to prevent the onset of early stages of chronic kidney disease in individuals with diabetes. Better management of CKD can slow the progression of CKD, prevent complications, and reduce cardiovascular-related outcomes and improve patient’s quality of life. Key words: chronic kidney disease, Glomerular filtration rate, Hypertension, Diabetes mellitus, Drug related problem, Angiotensin converting enzyme inhibitor, end stage renal disease, National Kidney Foundation, quality of life

Identification of Stk25 as a genetic modifier of Tau phosphorylation in Dab1-mutant mice.

Hyperphosphorylation of the microtubule binding protein Tau is a feature of a number of neurodegenerative diseases, including Alzheimer's disease. Tau is hyperphosphorylated in the hippocampus of dab1-null mice in a strain-dependent manner; however, it has not been clear if the Tau phosphorylation phenotype is a secondary effect of the morbidity of these mutants. The dab1 gene encodes a docking protein that is required for normal brain lamination and dendritogenesis as part of the Reelin signaling pathway. We show that dab1 gene inactivation after brain development leads to Tau hyperphosphorylation in anatomically normal mice. Genomic regions that regulate the phospho Tau phenotype in dab1 mutants have previously been identified. Using a microarray gene expression comparison between dab1-mutants from the high-phospho Tau expressing and low-phospho Tau expressing strains, we identified Stk25 as a differentially expressed modifier of dab1-mutant phenotypes. Stk25 knockdown reduces Tau phosphorylation in embryonic neurons. Furthermore, Stk25 regulates neuronal polarization and Golgi morphology in an antagonistic manner to Dab1. This work provides insights into the complex regulation of neuronal behavior during brain development and provides insights into the molecular cascades that regulate Tau phosphorylation

PREVALENCE AND IMPACT OF HEAVY MENSTRUAL BLEEDING: A REVIEW

Menorrhagia is the most common complaint among female reproductive ages. It has been defined as excessive menstrual blood loss more than 80ml and it affects the woman’s physical, social and emotional status. Symptoms of menorrhagia may include, soaking through one or more sanitary pads every hour for several consecutive hours and bleeding for longer than a week. Counselling is necessary for its management. In adolescence females undergo many physical and psychological changes. Patients presenting with menstrual irregularities must be screened properly as incidence of menorrhagia is high in reproductive age women. Frequency of menstrual disorders and their impact on women’s health status, quality of life and social integration suggest that proper evaluation and management should be given a higher priority. Key words: Heavy menstrual bleeding, excessive bleeding, menstrual cycle, menorrhagi

The Golgi extension and neuronal polarization phenotypes in <i>dab1</i> mutant neurons is dependent upon mouse strain background.

<p>The appearance of the Golgi apparatus was examined in 100 µm thick sections of the hippocampus at birth by immunostaining for GRASP65 and Ctip2 to identify pyramidal neurons. <b>A</b> In wild-type animals the Golgi apparatus extends several microns into the presumptive apical dendrite in the hippocampi, but in C57BL/6 <i>dab1−/−</i> mutants it is convoluted near the nucleus. The Golgi appears more elongated in the Balb/c <i>dab1−/−</i> mutant mice. Nucleus to Golgi distances were measured on isolated cells (insets). Arrowheads represent points used for measurements. <b>B</b> The nucleus to Golgi tip distances are greater for wild-type than <i>dab1−/−</i> mutants, and greater for BALB/c versus C57BL/6 <i>dab1−/−</i> mutants (*,** p<0.0001, Student's t test). <b>C</b> The number of multiple axon bearing neurons in <i>dab1−/−</i> mutant neurons is reduced on the BALB/c background as compared to the C57BL/6 background. In both cases, knocking down Stk25 leads to a further reduction in neurons with multiple axons and the development of neurons with no axons (* p<0.001 compared to the respective EV-control samples, ** p = 0.01 compared between EV-control samples, Student's t test) (Bar = 20 µm) Values for C57BL/6 samples have been published previously <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031152#pone.0031152-Matsuki2" target="_blank">[34]</a> and are shown here for comparison to BALB/c samples.</p

Stk25 expression is not correlated with augmented Tau phosphorylation in a Tauopathy model or in transfected HeLa cells.

<p><b>A</b> Lysates from brains of 9.5 month old wild-type or Tg4510 mutant animals were immunostained for Stk25 and β-actin (upper panel). The average Stk25 signal normalized to β-actin from 3 separate samples from each genotype showed no statistically significant difference (lower panel). <b>B</b> Overexpression of Stk25-GFP did not lead to increased phosphorylation of co-transfected Tau in HeLa cells. Antibodies used for Westerns indicated at left: AT8 (phospho Ser202/Thr205 Tau) 5E2 total Tau. Sizes of expected Stk25-GFP and endogenous Stk25 are indicated at right.</p

Stk25 mRNA and protein levels are strain-dependent.

<p><b>A</b> Stk25 mRNA expression was 1.8-fold higher in C57BL/6 versus BALB/c strain in <i>dab1</i> −/− and wild-type mice by real-time PCR. <b>B</b> Western blot analysis of Stk25 protein levels showed higher levels of expression in <i>dab1</i> −/− and wild-type mutant animals on the C57BL/6 than the BALB/c strain. <b>C</b> Representative anti-Stk25 (upper panel) and anti-actin (lower panel) Western blots of hippocampal lysates.</p

Characterization of genes that are differentially expressed between C57BL6 and BALB/c background Dab1 mutant mice and map to the Tau phosphorylation QTL on chromosome 1.

<p>The QTL at D1Mit365 segregates with Tau hyperphosphorylation in <i>dab1</i>−/− mutant mice. We identified 7 differentially expressed genes that map between markers that define the outer limits of the QTL (D1Mit215-D1Mit90). One of these, Stk25, was considered a good candidate since it encoded a serine/threonine kinase. Gene expression differences for <i>dab1−/−</i> mutant animals are shown for C57BL/6 versus BALB/c backgrounds (negative value indicates higher expression in BALB/c).</p

Stk25 knockdown reduces Tau phosphorylation in embryonic neurons.

<p><b>A</b> Phospho-Tau normalized to total Tau was significantly reduced in primary neurons infected with Stk25 shRNA viruses compared to neurons infected with either an empty vector (EV)-control or the control shRNA (con shRNA). <b>B</b> Tau phosphorylation at pSer202/pThr205 (AT8 antibody, 1^st panel) was lower in samples with reduced Stk25 expression (3^rd panel), whereas total Tau levels (2^nd panel) and β-actin levels (4^th panel) were unchanged. (* p<0.05, Student's t test, n = 3).</p