Microalbuminuria as an overrated indicator of target organ damage in hypertension: a hospital based cross sectional study

Background:Hypertension is one of the leading causes of global burden of disease. Uncontrolled hypertension is associated with long term risk of damage to vital organs like brain, heart, kidney, blood vessels and eye i.e. Target Organ Damage (TOD). Medical scientists all over the world have been in search for an indicator which can accurately predict TOD. It is accepted that Microalbuminuria (MA) represents a more generalised vascular problem, not only confined to renal microcirculation. MA is found in a significant proportion of non-diabetic population, particularly in association with hypertension and is a predictor of cardiovascular disease. The objective of the study was to evaluate MA in hypertension and its correlation with TOD.  Methods:A Hospital based cross sectional study carried out in the department medicine of central referral hospital, a well-equipped tertiary care hospital in East Sikkim, Gangtok. 200 patients were recruited fulfilling the inclusion criteria of pre hypertension, stage 1 & 2 hypertension as defined by JNC 7 report. Patients with secondary hypertension, DM, ESRD & hyperuricemia were excluded.  MA was estimated by Immunoturbidimetry.Results:MA is associated with all TOD but significant correlation was found only with retinopathy. Out of 200 study subjects, 90 (45%) subjects had retinopathy out of which 54 (60%) had MA and 36 (40%) did not have MA. (P <0.0001)Conclusion:MA has established its position in DM where it indicates early end organ damage and heralds cardiovascular risk. Its role as a reliable indicator of TOD in non-diabetic hypertensives needs further evaluation.

Urothelial Plaque Formation in Post-Golgi Compartments

Urothelial plaques are specialized membrane domains in urothelial superficial (umbrella) cells, composed of highly ordered uroplakin particles. We investigated membrane compartments involved in the formation of urothelial plaques in mouse umbrella cells. The Golgi apparatus did not contain uroplakins organized into plaques. In the post-Golgi region, three distinct membrane compartments containing uroplakins were characterized: i) Small rounded vesicles, located close to the Golgi apparatus, were labelled weakly with anti-uroplakin antibodies and they possessed no plaques; we termed them “uroplakin-positive transporting vesicles” (UPTVs). ii) Spherical-to-flattened vesicles, termed “immature fusiform vesicles” (iFVs), were uroplakin-positive in their central regions and contained small urothelial plaques. iii) Flattened “mature fusiform vesicles” (mFVs) contained large plaques, which were densely labelled with anti-uroplakin antibodies. Endoytotic marker horseradish peroxidase was not found in these post-Golgi compartments. We propose a detailed model of de novo urothelial plaque formation in post-Golgi compartments: UPTVs carrying individual 16-nm particles detach from the Golgi apparatus and subsequently fuse into iFV. Concentration of 16-nm particles into plaques and removal of uroplakin-negative membranes takes place in iFVs. With additional fusions and buddings, iFVs mature into mFVs, each carrying two urothelial plaques toward the apical surface of the umbrella cell

Genetic Incorporation of Human Metallothionein into the Adenovirus Protein IX for Non-Invasive SPECT Imaging

As the limits of existing treatments for cancer are recognized, clearly novel therapies must be considered for successful treatment; cancer therapy using adenovirus vectors is a promising strategy. However tracking the biodistribution of adenovirus vectors in vivo is limited to invasive procedures such as biopsies, which are error prone, non-quantitative, and do not give a full representation of the pharmacokinetics involved. Current non-invasive imaging strategies using reporter gene expression have been applied to analyze adenoviral vectors. The major drawback to approaches that tag viruses with reporter genes is that these systems require initial viral infection and subsequent cellular expression of a reporter gene to allow non-invasive imaging. As an alternative to conventional vector detection techniques, we developed a specific genetic labeling system whereby an adenoviral vector incorporates a fusion between capsid protein IX and human metallothionein. Our study herein clearly demonstrates our ability to rescue viable adenoviral particles that display functional metallothionein (MT) as a component of their capsid surface. We demonstrate the feasibility of 99mTc binding in vitro to the pIX-MT fusion on the capsid of adenovirus virions using a simple transchelation reaction. SPECT imaging of a mouse after administration of a 99mTc-radiolabeled virus showed clear localization of radioactivity to the liver. This result strongly supports imaging using pIX-MT, visualizing the normal biodistribution of Ad primarily to the liver upon injection into mice. The ability we have developed to view real-time biodistribution in their physiological milieu represents a significant tool to study adenovirus biology in vivo

Deregulation of Rab and Rab Effector Genes in Bladder Cancer

Growing evidence indicates that Rab GTPases, key regulators of intracellular transport in eukaryotic cells, play an important role in cancer. We analysed the deregulation at the transcriptional level of the genes encoding Rab proteins and Rab-interacting proteins in bladder cancer pathogenesis, distinguishing between the two main progression pathways so far identified in bladder cancer: the Ta pathway characterized by a high frequency of FGFR3 mutation and the carcinoma in situ pathway where no or infrequent FGFR3 mutations have been identified. A systematic literature search identified 61 genes encoding Rab proteins and 223 genes encoding Rab-interacting proteins. Transcriptomic data were obtained for normal urothelium samples and for two independent bladder cancer data sets corresponding to 152 and 75 tumors. Gene deregulation was analysed with the SAM (significant analysis of microarray) test or the binomial test. Overall, 30 genes were down-regulated, and 13 were up-regulated in the tumor samples. Five of these deregulated genes (LEPRE1, MICAL2, RAB23, STXBP1, SYTL1) were specifically deregulated in FGFR3-non-mutated muscle-invasive tumors. No gene encoding a Rab or Rab-interacting protein was found to be specifically deregulated in FGFR3-mutated tumors. Cluster analysis showed that the RAB27 gene cluster (comprising the genes encoding RAB27 and its interacting partners) was deregulated and that this deregulation was associated with both pathways of bladder cancer pathogenesis. Finally, we found that the expression of KIF20A and ZWINT was associated with that of proliferation markers and that the expression of MLPH, MYO5B, RAB11A, RAB11FIP1, RAB20 and SYTL2 was associated with that of urothelial cell differentiation markers. This systematic analysis of Rab and Rab effector gene deregulation in bladder cancer, taking relevant tumor subgroups into account, provides insight into the possible roles of Rab proteins and their effectors in bladder cancer pathogenesis. This approach is applicable to other group of genes and types of cancer

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

<smarttagtype namespaceuri="urn:schemas-microsoft-com:office:smarttags" name="place"> Use of medicinal plants among tribes in Satpuda region of Dhule and Jalgaon districts of Maharashtra—An ethnobotanical survey </smarttagtype>

152-157 An ethnobotanical survey was carried out on the use of medicinal plants in Satpuda region of Dhule and Jalgaon districts of Maharashtra. The information was gathered from Pawara, Bhil and Pardhi tribes using an integrated approach of botanical collections, group discussions and interviews with questionnaire during 2004-2005. Among 50 informants interviewed, 8 were tribal practitioners. A total of 67 medicinal plant species distributed in 37 families are documented. In most of the cases, fresh part of the plant was used for the preparation of medicine. These tribal people still depend on the medicinal plants to cure their diseases and disorders in Satpuda forest region. The documented ethnomedicinal plants were mostly used to cure wound infections, skin infections, stomachache, fever, cough, diabetes, diuretics, diarrhoea, eye infections and general weakness. </smarttagtype

Comparative phytochemical analysis and antioxidant activity of triphala Mashi and triphala

No Abstract.Nigerian Journal of Natural Products and Medicine Vol. 10 () 2006: pp.73-7

Diuretic activity of coconut husk <i style="">Mashi</i>—an Ayurvedic formulation

471-473Coconut husk Mashi is an Ayurvedic formulation prepared by Anterdhum Padhati (APM) and Bahirdhum Padhati (BPM). Though, Ayurvedic practitioners use coconut husk Mashi for diuretic activity, no systematic studies are reported with regard to the verification of the traditional medicinal claims of Mashi. The present study was undertaken to investigate and rationalize the diuretic activity of APM and BPM in experimental rats. The diuretic properties of APM and BPM were evaluated by determination of urine volume, electrolyte concentration and diuretic potency in male albino rats. Different concentrations of Mashi (250 mg/kg, 500 mg/kg) were orally administered to hydrated rats and their urine output was immediately measured after 5hrs of treatment. Frusemide (10 mg/kg) was used as reference drug while normal saline (0.9%) solution was used as control. BPM exhibited dose dependent diuretic property and APM failed to show activity. The onset of diuretic action was extremely prompt (within 1hr) and lasted throughout the study period (up to 5 hrs). BPM at 500 mg/kg displayed highest activity with potency value of 0.92 and same dose of APM gave a value of 0.24. BPM caused mark increased in Na+, K+ and Cl- level. The results suggest that BPM possess significant diuretic activity