Metabolic effect of telmisartan and losartan in hypertensive patients with metabolic syndrome

Background

Metabolic syndrome is a cluster of common cardiovascular risk factors that includes hypertension and insulin resistance. Hypertension and diabetes mellitus are frequent comorbidities and, like metabolic syndrome, increase the risk of cardiovascular events. Telmisartan, an antihypertensive agent with evidence of partial peroxisome proliferator-activated receptor activity-gamma (PPARγ) activity, may improve insulin sensitivity and lipid profile in patients with metabolic syndrome.

Methods

In a double-blind, parallel-group, randomized study, patients with World Health Organization criteria for metabolic syndrome received once-daily doses of telmisartan (80 mg, n = 20) or losartan (50 mg, n = 20) for 3 months. At baseline and end of treatment, fasting and postprandial plasma glucose, insulin sensitivity, glycosylated haemoglobin (HBA_1c) and 24-hour mean systolic and diastolic blood pressures were determined.

Results

Telmisartan, but not losartan, significantly (p < 0.05) reduced free plasma glucose, free plasma insulin, homeostasis model assessment of insulin resistance and HbA_ic. Following treatment, plasma glucose and insulin were reduced during the oral glucose tolerance test by telmisartan, but not by losartan. Telmisartan also significantly reduced 24-hour mean systolic blood pressure (p < 0.05) and diastolic blood pressure (p < 0.05) compared with losartan.

Conclusion

As well as providing superior 24-hour blood pressure control, telmisartan, unlike losartan, displayed insulin-sensitizing activity, which may be explained by its partial PPARγ activity.     

Thymol derivatives from Eupatorium glechonophyllum

The known 10-acetoxy-8,9-epoxythymolisobutyrate and the new 8,9-dihydroxy-10-acetoxythymolisobutyrate and 8,9,10-trihydroxythymol have been isolated from the thallus of Eupatorium glechonophyllum. The acetonide of the last compound was also obtained. The possibility that the new compounds are artefacts is discussed.     

Interactions between natural killer cells and antibody Fc result in enhanced antibody neutralization of human immunodeficiency virus type 1

Antibodies can prevent lentivirus infections in animals and may play a role in controlling viral burden in established infection. In preventing and particularly in controlling infection, antibodies likely function in the presence of large quantities of virus. In this study, we explored the mechanisms by which antibodies neutralize large inocula of human immunodeficiency virus type 1 (HIV-1) on different target cells. Immunoglobulin G (IgG) from HIV-infected patients was tested for neutralizing activity against primary R5 strains of HIV-1 at inocula ranging from 100 to 20,000 50% tissue culture infective doses. At all virus inocula, inhibition by antibody was enhanced when target cells for virus growth were monocyte-depleted, peripheral blood mononuclear cells (PBMCs) rather than CD4(+) lymphocytes. However, enhanced inhibition on PBMCs was greatest with larger amounts of virus. Depleting PBMCs of natural killer (NK) cells, which express Fc receptors for IgG (FcgammaRs), abrogated the enhanced antibody inhibition, whereas adding NK cells to CD4(+) lymphocytes restored inhibition. There was no enhanced inhibition on PBMCs when F(ab')(2) was used. Further experiments demonstrated that the release of beta-chemokines, most likely through FcgammaR triggering of NK cells, contributed modestly to the antiviral activity of antibody on PBMCs and that antibody-coated virus adsorbed to uninfected cells provided a target for NK cell-mediated inhibition of HIV-1. These results indicate that Fc-FcgammaR interactions enhance the ability of antibody to neutralize HIV-1. Since FcgammaR-bearing cells are always present in vivo, FcgammaR-mediated antibody function may play a role in the ability of antibody to control lentivirus infection.     

Anatomical and molecular characterization of Lactarius aff. omphaliformis, Russula alnijorullensis and Cortinarius tucumanensis ectomycorrhizae on Alnus acuminata

Ectomycorrhizae (ECM) of Lactarius aff. omphaliformis Romagn., Russula alnijorullensis (Sing.) Sing. and Cortinarius tucumanensis Mos. on Andean alder (Alnus acuminata Kunth) were characterized and identified. The identification of the fungal symbionts was achieved by morpho-anatomical observations of mycorrhizae and by comparison of ITS-RFLP patterns obtained from ECM and fruitbodies. L. aff omphaliformis ECM differed in some morphological details such as ramification and mantle type from ECM of the same species on A. glutinosa. L. aff omphaliformis ECM show an orange to ochre mantle containing latex cells, which stain with sulpho-vanillin, emanating hyphae without clamps. R. alnijorullensis ECM represent a typical Russula-type-ECM, light yellow to pinkish, the outer mantle being composed of triangular latex-filled cells staining with sulpho-vanillin, emanating hyphae without clamps. C. tucumanensis ECM exhibit a white (silvery) to yellowish brown mantle covered with soil particles, emanating hyphae with clamps.     

Functional characterization of KlHEM13, a hypoxic gene of Kluyveromyces lactis

The KlHEM13 gene of Kluyveromyces lactis encoding the coproporphyrinogen oxidase (EC 1.3.3.3), an oxygen-requiring enzyme that catalyzes the sixth step of heme biosynthesis, was cloned and functionally characterized. The coding and upstream regions of KlHEM13 were analyzed and the putative cis regulatory elements were discussed in relation to the mechanisms of regulation of this hypoxic gene in K. lactis.     

Lipids and DNA oxidation in Staphylococcus aureus as a consequence of oxidative stress generated by ciprofloxacin

Ciprofloxacin induced an increment of reactive oxygen species in sensitive strains of Staphylococcus aureus leading to oxidative stress detected by chemiluminescence while resistant strains did not suffer such stress. Oxidation of lipids was performed by employing thiobarbituric acid reaction to detect the formation of the amplified intermediate between reactive species oxygen and cytoplasmic macromolecules, namely malondialdehyde (MDA). The sensitive strain presented higher peroxidation of lipids than the resistant strain. The oxidative consequence for DNA was investigated by means of bacteria incubation with ciprofloxacin and posterior extraction of DNA, which was studied by high performance liquid chromatography (HPLC). Sensitive S. aureus ATCC 29213 showed an increase of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) respect controls without antibiotic; there was evident increase of the ratio between 8-oxodG and deoxyguanosine (dG) as a consequence of oxidation of dG to 8-oxodG considered the major DNA marker of oxidative stress. The resistant strain showed low oxidation of DNA and the analysis of 8-oxodG/dG ratio indicated lesser formation of 8-oxodG than S. aureus ATCC 29213.     

Human CD4+ T cell response to human herpesvirus 6

Following primary infection, human herpesvirus 6 (HHV-6) establishes a persistent infection for life. HHV-6 reactivation has been associated with transplant rejection, delayed engraftment, encephalitis, muscular dystrophy, and drug-induced hypersensitivity syndrome. The poor understanding of the targets and outcome of the cellular immune response to HHV-6 makes it difficult to outline the role of HHV-6 in human disease. To fill in this gap, we characterized CD4 T cell responses to HHV-6 using peripheral blood mononuclear cell (PBMC) and T cell lines generated from healthy donors. CD4(+) T cells responding to HHV-6 in peripheral blood were observed at frequencies below 0.1% of total T cells but could be expanded easily in vitro. Analysis of cytokines in supernatants of PBMC and T cell cultures challenged with HHV-6 preparations indicated that gamma interferon (IFN-γ) and interleukin-10 (IL-10) were appropriate markers of the HHV-6 cellular response. Eleven CD4(+) T cell epitopes, all but one derived from abundant virion components, were identified. The response was highly cross-reactive between HHV-6A and HHV-6B variants. Seven of the CD4(+) T cell epitopes do not share significant homologies with other known human pathogens, including the closely related human viruses human herpesvirus 7 (HHV-7) and human cytomegalovirus (HCMV). Major histocompatibility complex (MHC) tetramers generated with these epitopes were able to detect HHV-6-specific T cell populations. These findings provide a window into the immune response to HHV-6 and provide a basis for tracking HHV-6 cellular immune responses.     

Molecular mapping of a new source of Fusarium wilt resistance in tetraploid cotton (Gossypium hirsutum L.)

Fusarium wilt (FW) disease is an economically important disease of cotton worldwide and a major cause of crop losses in Australia and many other cotton-producing countries. Symptoms include wilting, vascular browning and death. Australian races of the causal agent Fusarium oxysporum f. sp. vasinfectum (Fov) are genetically distinct from those in other countries and are thought to have evolved from indigenous races. New sources of resistance for breeding are rare, as cotton cultivars with significant FW resistance against Fov isolates from other cotton-producing regions are usually susceptible to Australian Fov races. MCU-5, an Upland Indian cotton cultivar, has been identified as having improved resistance to Australian Fov and is being used to breed new commercial cultivars with higher resistance to FW. To investigate the genetic basis of the FW resistance in MCU-5, QTL analysis was performed on 244 F3 and 244 F4 families derived from an intraspecific cross between MCU-5 and Siokra 1-4, a cultivar highly sensitive to Australian Fov races. Resistance, as measured by leaf symptoms, vascular browning and survival, showed low to moderate heritability between generations. MCU-5 resistance to FW was found to be complex with three quantitative trait loci (QTL) identified in the F3, and eight in the F4, that explained between 9 and 41% of the phenotypic variation. The QTL were located on four linkage groups including chromosomes A6 (Chr 6), D4 (Chr 22) and D6 (Chr 25), with two QTL located in similar regions to previously identified FW resistance from the Sea Island cultivar Pima 3-79. The QTL identified in this study represent the first targets for marker-assisted selection of FW resistance in Australia.     

Sources and sinks of diversification and conservation priorities for the Mexican tropical dry forest

Elucidating the geographical history of diversification is critical for inferring where future diversification may occur and thus could be a valuable aid in determining conservation priorities. However, it has been difficult to recognize areas with a higher likelihood of promoting diversification. We reconstructed centres of origin of lineages and identified areas in the Mexican tropical dry forest that have been important centres of diversification (sources) and areas where species are maintained but where diversification is less likely to occur (diversity sinks). We used a molecular phylogeny of the genus Bursera, a dominant member of the forest, along with information on current species distributions. Results indicate that vast areas of the forest have historically functioned as diversity sinks, generating few or no extant Bursera lineages. Only a few areas have functioned as major engines of diversification. Long-term preservation of biodiversity may be promoted by incorporation of such knowledge in decision-making.