Calcium-and integrin-binding protein regulates focal adhesion kinase activity during platelet spreading on immobilized fibrinogen

Platelet spreading on the subendothelium in response to vascular injury is fundamental to the regulation of physiologic hemostasis. Previously, we have shown that, when bound to glycoprotein IIb (GPIIb), calcium- and integrin-binding protein (CIB) regulates platelet spreading on immobilized fibrinogen (Fg). In this study, we investigated the signaling events that occur downstream of CIB in the absence of signaling that occurs as a result of granular secretion. Using Chinese hamster ovary (CHO) cells as a model, we demonstrate that CIB induces cell migration. Immunofluorescence analysis of CIB localization indicates that endogenous CIB accumulates in areas of focal adhesions, and its overexpression up-regulates the formation of focal adhesion complexes compared with control cells. Immunoprecipitation analysis indicates that CIB associates with focal adhesion kinase (FAK), a key regulator in focal complex formation, and up-regulates its activity. Overexpression of dominant-negative FAK, FRNK, along with CIB in CHO cells completely inhibits CIB-induced cell migration. Further, confirmation of these data in the platelet system indicates that CIB and FAK associate throughout all stages of platelet spreading but only on Fg binding to GPIIb/IIIa. Taken together, our results suggest that CIB regulates platelet spreading through the regulation of FAK activation.     

Studies with trimipramine on isolated kitten atria.

The effect of different doses of trimipramine has been studied on the force of contraction of isolated kitten atria. Trimipramine produced dose dependent increase in the force of contraction of the atria. Pretreatment of kitten with reserpine or of the isolated atria with propranolol inhibited the positive inotropic effect of trimpramine. The positive inotropic action of trimipramine is probably due to the release and /or due to blocking the uptake of spontaneously released noradrenaline. Trimipramine was also found to potentiate the positive inotropic action of noradrenaline. This potentiation not only decreased in relation to the time of exposure of the isolated atria to trimipramine but also the action of noradrenaline was antagonised.     

Safety assessment of lutein and zeaxanthin (Lutemax™ 2020): Subchronic toxicity and mutagenicity studies

Lutein and zeaxanthin, naturally occurring carotenoids, have shown to reduce the risk of cataracts and age-related macular degeneration. Lutemax™ 2020 is a lutein and zeaxanthin (including meso-isomer) enriched product obtained from Marigold flowers (Tagetes erecta L). The objective of the present study was to investigate adverse effects, if any, of Lutemax 2020™ in acute and subchronic toxicity, and mutagenicity studies. In acute toxicity study in rats no lethality was noted at 2000 mg Lutemax 2020™/kg body weight (bw). In the subchronic study, Wistar rats (10/sex/group) were administered (gavage) lutein/zeaxanthin concentrate at dose levels of 0, 4, 40 and 400 mg/kg bw/day for 90-days. Compared with the control group, administration of lutein/zeaxanthin concentrate did not result in any toxicologically significant treatment-related changes in clinical observations, ophthalmic examinations, body weights, body weight gains, feed consumption, and organ weights. No toxicologically relevant findings were noted in urinalysis, hematology or clinical biochemistry parameters at the end of the treatment or recovery period. Terminal necropsy did not reveal any treatment-related gross or histopathology findings. The results of mutagenicity testing in Salmonella typhimurium did not reveal any genotoxicity. The no observed-adverse-effect level (NOAEL) for lutein/zeaxanthin concentrate was determined as 400 mg/kg bw/day, the highest dose tested.     

Larvicidal potential of silver nanoparticles synthesized using fungus Cochliobolus lunatus against Aedes aegypti (Linnaeus, 1762) and Anopheles stephensi Liston (Diptera; Culicidae)

Larvicides play a vital role in controlling mosquitoes in their breeding sites. The present study was carried out to establish the larvicidal activities of mycosynthesized silver nanoparticles (AgNPs) against vectors: Aedes aegypti and Anopheles stephensi responsible for diseases of public health importance. The AgNPs synthesized by filamentous fungus Cochliobolus lunatus, characterized by UV–Vis spectrophotometry, Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, and transmission electron microscopy. The characterization studies confirmed the spherical shape and size (3–21 nm) of silver nanoparticles. The efficacy of mycosynthesized AgNPs at all the tested concentrations (10, 5, 2.5, 1.25, 0.625, and 0.3125 ppm) against second, third, and fourth instar larvae of A. aegypti (LC₅₀ 1.29, 1.48, and 1.58; LC₉₀ 3.08, 3.33, and 3.41 ppm) and against A. stephensi (LC₅₀ 1.17, 1.30, and 1.41; LC₉₀ 2.99, 3.13, and 3.29 ppm) were observed, respectively. The mortality rates were positively correlated with the concentration of AgNPs. Significant (P < 0.05) changes in the larval mortality was also recorded between the period of exposure against fourth instar larvae of A. aegypti and A. stephensi. The possible larvicidal activity may be due to penetration of nanoparticles through membrane. Toxicity studies carried out against non-target fish species Poecilia reticulata, the most common organism in the habitats of A. aegypti and A. stephensi showed no toxicity at LC50 and LC90 doses of the AgNPs. This is the first report on mosquito larvicidal activity of mycosynthesized nanoparticles. Thus, the use of fungus C. lunatus to synthesize silver nanoparticles is a rapid, eco-friendly, and a single-step approach and the AgNps formed can be potential mosquito larvicidal agents.     

Prevalence of antibodies to hepatitis C virus in HBsAg negative hemodialysis patients.

The prevalence of hepatitis C virus (HCV) infection was estimated in a 14-month study using anti-C100-3 antibody assay in 31 HBsAg negative patients on maintenance hemodialysis (MHD) for > or = 3 months. One and three patients respectively had ALT elevation and anti-HCV positivity at entry. During MHD (mean period of follow up 9.9 mo), 11 (35.5%) patients had, on fortnightly estimation, ALT elevation which lasted for < or = 6 months in seven patients and for > 6 months in four. Fourteen (45.2%) patients had anti-HCV (including the three positive at entry). There was no significant difference in frequency of anti-HCV positivity in patients with normal and elevated ALT (57.1% and 42.9% respectively). The number of blood transfusions and duration of MHD were similar in anti-HCV positive and anti-HCV negative patients. We conclude that our MHD patients have a high frequency of hepatitis and anti-HCV positivity, and these may not be related to blood transfusions.