Drug and Alcohol Rehabilitation: Effect of Eplerenone, a Selective Aldosterone Blocker, on the Development of Diabetic Nephropathy in Type 2 Diabetic Rats.

Effect of eplerenone, a selective aldosterone blocker, on the development of diabetic nephropathy in type 2 diabetic rats.

Filed under: Drug and Alcohol Rehabilitation

Diabetes Metab J. 2012 Apr; 36(2): 128-35
Ahn JH, Hong HC, Cho MJ, Kim YJ, Choi HY, Eun CR, Yang SJ, Yoo HJ, Kim HY, Seo JA, Kim SG, Choi KM, Baik SH, Choi DS, Kim NH

Aldosterone antagonists are reported to have beneficial effects on diabetic nephropathy by effective blocking of the renin-angiotensin-aldosterone system. We investigated the renoprotective effect of the selective aldosterone receptor blocker eplerenone, the angiotensin converting enzyme inhibitor lisinopril, and combined eplerenone and lisinopril treatment in type 2 diabetic rats.ANIMALS WERE DIVIDED INTO SIX GROUPS AS FOLLOWS: Otsuka Long-Evans Tokushima Fatty (OLETF) rat control, OLETF rats treated with a low dose of eplerenone (50 mg/kg/day), OLETF rats treated with a high dose of eplerenone (200 mg/kg/day), OLETF rats treated with lisinopril (10 mg/kg/day), OLETF rats treated with a combination of both drugs (eplerenone 200 mg/kg/day and lisinopril 10 mg/kg/day), and obese non-diabetic Long-Evans Tokushima Otsuka rats for 26 weeks.Urinary albumin excretion was significantly lower in the lisinopril group, but not in the eplerenone group. Urinary albumin excretion was decreased in the combination group than in the lisinopril group. Glomerulosclerosis and renal expression of type I and type IV collagen, plasminogen activator inhibitor-1, transforming growth factor-?1, connective tissue growth factor, and fibronectin mRNA were markedly decreased in the lisinopril, eplerenone, and combination groups.Eplerenone and lisinopril combination showed additional benefits on type 2 diabetic nephropathy compared to monotherapy of each drug.
HubMed – drug


Role of H- and D- MATE-Type Transporters from Multidrug Resistant Clinical Isolates of Vibrio fluvialis in Conferring Fluoroquinolone Resistance.

Filed under: Drug and Alcohol Rehabilitation

PLoS One. 2012; 7(4): e35752
Mohanty P, Patel A, Kushwaha Bhardwaj A

The study seeks to understand the role of efflux pumps in multidrug resistance displayed by the clinical isolates of Vibrio fluvialis, a pathogen known to cause cholera-like diarrhoea.Two putative MATE family efflux pumps (H- and D-type) were PCR amplified from clinical isolates of V. fluvialis obtained from Kolkata, India, in 2006 and sequenced. Bioinformatic analysis of these proteins was done to predict protein structures. Subsequently, the genes were cloned and expressed in a drug hypersusceptible Escherichia coli strain KAM32 using the vector pBR322. The recombinant clones were tested for the functionality of the efflux pump proteins by MIC determination and drug transport assays using fluorimeter.The sequences of the genes were found to be around 99% identical to their counterparts in V. cholerae. Protein structure predicting servers TMHMM and I-TASSER depicted ten-twelve membrane helical structures for both type of pumps. Real time PCR showed that these genes were expressed in the native V. fluvialis isolates. In the drug transport assays, the V. fluvialis clinical isolates as well as recombinant E. coli harbouring the efflux pump genes showed the energy-dependent and sodium ion-dependent drug transport activity. KAM32 cells harbouring the recombinant plasmids showed elevated MIC to the fluoroquinolones, norfloxacin and ciprofloxacin but H-type pumps VCH and VFH from V. cholerae and V. fluvialis respectively, showed decreased MIC to aminoglycosides like gentamicin, kanamycin and streptomycin. Decrease in MIC was also observed for acriflavin, ethidium bromide, safranin and nalidixic acid.Increased resistance towards fluoroquinolones exhibited due to these efflux pumps from multidrug resistant clinical isolates of V. fluvialis implies that treatment procedure may become more elaborate for this simple but highly infectious disease. To the best of our knowledge, this is the first report of cloning and characterization of efflux pumps from multidrug resistant clinical isolates of V. fluvialis.
HubMed – drug


Evaluation of Leishmania donovani Protein Disulfide Isomerase as a Potential Immunogenic Protein/Vaccine Candidate against Visceral Leishmaniasis.

Filed under: Drug and Alcohol Rehabilitation

PLoS One. 2012; 7(4): e35670
Kushawaha PK, Gupta R, Tripathi CD, Sundar S, Dube A

In Leishmania species, Protein disulfide isomerase (PDI) – a redox chaperone, is reported to be involved in its virulence and survival. This protein has also been identified, through proteomics, as a Th1 stimulatory protein in the soluble lysate of a clinical isolate of Leishmania donovani (LdPDI). In the present study, the molecular characterization of LdPDI was carried out and the immunogenicity of recombinant LdPDI (rLdPDI) was assessed by lymphocyte proliferation assay (LTT), nitric oxide (NO) production, estimation of Th1 cytokines (IFN-? and IL-12) as well as IL-10 in PBMCs of cured/endemic/infected Leishmania patients and cured L. donovani infected hamsters. A significantly higher proliferative response against rLdPDI as well as elevated levels of IFN-? and IL-12 were observed. The level of IL-10 was found to be highly down regulated in response to rLdPDI. A significant increase in the level of NO production in stimulated hamster macrophages as well as IgG2 antibody and a low level of IgG1 in cured patient’s serum was observed. Higher level of IgG2 antibody indicated its Th1 stimulatory potential. The efficacy of pcDNA-LdPDI construct was further evaluated for its prophylactic potential. Vaccination with this construct conferred remarkably good prophylactic efficacy (?90%) and generated a robust cellular immune response with significant increases in the levels of iNOS transcript as well as TNF-?, IFN-? and IL-12 cytokines. This was further supported by the high level of IgG2 antibody in vaccinated animals. The in vitro as well as in vivo results thus indicate that LdPDI may be exploited as a potential vaccine candidate against visceral Leishmaniasis (VL).
HubMed – drug


Benchmark Recovery Center to be featured on hit show, The Doctors

Filed under: Drug and Alcohol Rehabilitation

Benchmark Recovery Center (BRC) is dedicated to carrying out Mark Houston's vision of providing long-term, intensive drug and alcohol recovery programs for men and women with a focus on a recovery-oriented system of care. And with a documented success …
Read more on Empowered News (press release)


Prescription Pill Addiction Behind the Orange Curtain; OC Drug Rehab

Filed under: Drug and Alcohol Rehabilitation

Orange County drug and alcohol treatment center 449 Recovery, based in San Clemente, CA, has been on the front lines of this battleground for decades, and has seen the tragic casualties that have been wrought by its aftermath.
Read more on PR Web (press release)


The Shoreline: Living Too Close to The Edge Results in Falling Off

Filed under: Drug and Alcohol Rehabilitation

Nowadays, we hear about many celebrities who are losing their lives because of drug and alcohol overdose. Even though they're legal, pharmaceutical drugs aren't any less dangerous than illicit drugs. Sometimes it takes high-profile cases to remind us …
Read more on my.hsj.org


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