Vasopeptidase inhibition affords greater renoprotection than angiotensin-converting enzyme inhibition alone

The renoprotective efficacy of the vasopeptidase inhibitor omapatrilat (OMA) was compared with that of enalapril (ENA) in male Munich-Wistar rats subjected to 5/6 nephrectomy. ENA and OMA administered beginning on day 2 after surgery were equally effective in normalizing systolic BP (SBP) and preventing glomerulosclerosis (GS) for 12 wk. Micropuncture studies of rats performed using a similar treatment protocol demonstrated greater reduction of glomerular capillary hydraulic pressure with OMA than with ENA, at similar mean arterial pressures. To investigate whether these glomerular hemodynamic differences might be associated with differences in chronic renoprotective efficacy, additional rats were included in a protocol in which treatment was delayed until 4 wk after surgery (after the onset of hypertension and proteinuria) and continued for a longer period. Both treatments normalized SBP, but OMA resulted in more sustained reduction of proteinuria than did ENA. At week 20, OMA- and ENA-treated rats exhibited less GS than did untreated (control) rats at week 12, but only the difference in control versus OMA values was statistically significant [GS scores: control (12 wk), 36 +/- 4%; ENA (20 wk), 22 +/- 6%; OMA (20 wk), 14 +/- 2%]. The remaining ENA-treated rats were euthanized at 32 wk because of rapidly increasing proteinuria, whereas the remaining OMA-treated rats demonstrated a substantially slower increase in proteinuria until euthanasia at 50 wk. At this extremely late time point, OMA-treated rats exhibited GS scores similar to those of ENA-treated rats at 32 wk and control rats at 12 wk [GS scores: ENA (32 wk), 34 +/- 5%; OMA (50 wk), 38 +/- 8%]. It is concluded that, in this model, OMA affords greater long-term renoprotection than ENA when doses are adjusted to yield equivalent control of SBP.     

Cytokine production-adenosine deaminase activity relationship in pulmonary tuberculosis

The serum activity of the enzyme adenosine desaminase (ADA) was studied in patients with infiltrative tuberculosis in relation to IL-1 beta, TNF-alpha, IL-2 productions, the magnitude of a lymphocytic proliferative response to PPD and PGA. There was an association of high ADA levels with the severity of a tuberculous process, with the least IL-2 production together with drastically increased IL1 beta and significant disorders in the TNF-alpha system. Moderate ADA increases reflect the regularly enhanced activity of immunocompetent cells in response to an infectious agent. The findings indicate that a simple biochemical test may be used for rapid preliminary evaluation of the severity of disease and immune performance.     

Quercetin Attenuates Benzo(α)pyrene-induced CYP1A Expression

<正>We studied effects of nutrient quercetin on cytochromes’Р450 1А(CYP1A)activities(measured spectrofluorimetrically using 7-ethoxy-resorufin for CYP1A1 and 7-methoxy-resorufin for CYP1A2 as substrates),on mR NA levels(measured by RT-PCR),and on DNA-binding activities(evaluated by an electrophoretic mobility shift assay)of proteins regulating CYP1A expression in untreated and benzo(α)pyrene(Ba P)-treated rats.Wistar rats