Ablation of Matrix Metalloproteinase-9 Prevents Cardiomyocytes Contractile Dysfunction in Diabetics

Elevated expression and activity of matrix metalloproteinase-9 (MMP9) and decreased contractility of cardiomyocytes are documented in diabetic hearts. However, it is unclear whether MMP is involved in the regulation of contractility of cardiomyocytes in diabetic hearts. In the present study, we tested the hypothesis that MMP9 regulates contractility of cardiomyocytes in diabetic hearts, and ablation of matrix metalloproteinase-9 (MMP9) prevents impaired contractility of cardiomyocytes in diabetic hearts. To determine the specific role of MMP9 in cardiomyocyte contractility, we used twelve - fourteen week male WT (normoglycemic sibling of Akita), Akita, and Ins2+/- /MMP9-/- (DKO) mice. DKO mice were generated by cross-breeding male Ins2+/- Akita (T1D) with female MMP9 knockout (MMP9-/-) mice. We isolated cardiomyocytes from the heart of the above three groups of mice and measured their contractility and calcium transients. Moreover, we determined mRNA and protein levels of sarco-endoplasmic reticulum calcium ATPase-2a (SERCA-2a), which is involved in calcium handling during contractility of cardiomyocytes, in WT, Akita, and DKO hearts using qPCR, Western blotting and immunoprecipitation, respectively. Our results revealed that in Akita hearts where increased expression and activity of MMP9 is reported, the rates of shortening and re-lengthening (± dL/dt) of cardiomyocytes were decreased, time to 90% peak height and baseline during contractility was increased, rate of calcium decay was increased, and calcium transient was decreased as compared to WT cardiomyocytes. However, these changes in Akita were blunted in DKO cardiomyocytes. The molecular analyses of SERCA-2a in the hearts showed that it was downregulated in Akita as compared to WT but was comparatively upregulated in DKO. These results suggest that abrogation of MMP9 gene prevents contractility of cardiomyocytes, possibly by increasing SERCA-2a and calcium transients. We conclude that MMP9 plays crucial role in the regulation of contractility of cardiomyocytes in diabetic hearts

Complex Formed by Interaction of Anthranilic Acid with Chromium(III) in Solution: A Kinetic Study

657-66

Not Available

Not AvailableThe study was conducted in crossbred Frieswal bulls (Holstein–Friesian X Sahiwal) during an outbreak of FMD and 24 FMD-affected animals were randomly divided into two groups–homeopathic treatment group and allopathic treatment group– consisting of 14 and 10 animals, respectively. Animals in the homeopathic treatment group were treated with Sulphur 200C @ 20 drops orally once, Kalium iodatum 200C @ 20 drops orally twice a day for 3 days. Calendula mother tincture was used for washing and topical application over the oral and foot lesions. Animals in the allopathic treatment group were treated with intramuscular injections of strepto-penicillin twice a day for 3 days, meloxicam once a day for 3 days along with washing of oral and foot lesions with potassium permanganate (1:1000) followed by topical application of 2% boroglycerine over the oral ulcers. The animals were closely inspected for 12 days for recording clinical signs. The mean rectal temperature in the animals of homeopathic treatment group was significantly (p<0.05) lower than those of the allopathic treatment group on days 2 and 3 post treatment. Appetite score improved significantly (p<0.05) in homeopathic treatment group as compared with allopathic treatment group on day 3 post treatment. Healing scores of oral mucosal lesion were significantly (p<0.05) higher in the homoeopathic treatment group than that in the allopathic treatment group on days 2, 3, and 5 post therapy. Healing of foot lesions was significantly (p<0.05) better in the homeopathic treatment group than that in the allopathic treatment group on day 3 and 5 post treatment.ICA

Monitoring the efficacy of antimalarial medicines in India via sentinel sites: Outcomes and risk factors for treatment failure

Background & objectives: To combat the problem of antimalarial drug resistance, monitoring the changes in drug efficacy over time through periodic surveillance is essential. Since 2009, systematic and continuous monitoring is being done through nationwide sentinel site system. Potential early warning signs like partner drug resistance markers were also monitored in the clinical samples from the study areas. Methods: A total of 1864 patients with acute uncomplicated malaria were enrolled in therapeutic efficacy studies of artesunate plus sulphadoxine-pyrimethamine (AS+SP) for Plasmodium falciparum; those infected with P. vivax were given chloroquine (CQ). Polymerase chain reaction (PCR) was used to distinguish post-treatment reinfection from treatment failures. Isolates of P. falciparum were also analysed for dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr) gene mutations. Results: Overall, 1687 (91.7%) patients completed the follow-up. In most of the falciparum patients the parasitaemia was cleared within 24 h of treatment, except 12 patients who remained parasite positive after 72 h. Presence of dhfr and dhps quintuple mutation was observed predominantly in treatment failure samples. A daily dose of artesunate of 95% cases in all the sentinel sites except in Northeastern region (NE). Chloroquine remained 100% efficacious in case of P. vivax infections. Interpretation & conclusion: Till 2012, India′s national antimalarial drug resistance monitoring system proved highly efficacious and safe towards first-line antimalarials used in the country, except in Northeastern region where a decline in efficacy of AS+SP has been observed. This led to change in first-line treatment for P. falciparum to artemether-lumefantrine in Northeastern region