A series of 1,2,4-oxadiazoles and 1,2,4-thiadiazoles containing a 2,6-di-tert-butylphenol substituent were prepared and evaluated as dual inhibitors of 5-lipoxygenase and cyclooxygenase in rat basophilic leukemia (RBL-1) cells. Several of these compounds show oral efficacy in the rat carrageenan footpad edema (CFE) and mycobacterium footpad edema (MFE) antiinflammatory models, without concomitant gastric ulceration. Structure-activity relationships are discussed. The best compounds (ID40 values in MFE of 3-8 mg/kg po) contain guanidine-derived substituents on the heterocyclic ring. 相似文献
This article has analyzed the pathogenesis of sodium and water retention in several circumstances. The initiator of retention has been proposed to be either a fall in cardiac output (e.g., low-output cardiac failure and vasoconstrictor hypovolemic nephrotic syndrome) or peripheral arterial vasodilatation (e.g., high-output cardiac failure, cirrhosis, arteriovenous fistula, and pregnancy). In the only state discussed, in which the kidney is diseased and not merely responding to extrarenal reflexes--i.e., nephrotic syndrome--intrarenal mechanisms may predominate and lead to expansion of the arterial vascular tree and suppression of the renin-angiotensin-aldosterone system (i.e., hypervolemic nephrotic syndrome). Otherwise, when kidneys are healthy, either a fall in cardiac output or peripheral arterial vasodilatation may diminish arterial vascular filling and thereby initiate a series of hemodynamic and hormonal events that result in renal sodium and water retention (Fig. 7). Finally, the approach presented in this article should be considered to be a vantage point from which to evaluate states of sodium and water retention, but not to be an exclusive position. 相似文献
Summary The pathogenesis of the diabetic glomerular lesion is unknown. However, cumulative indirect evidence favors hemodynamic factors associated with the abnormal endocrine environment as the cause of diabetic angiopathy. Experimental evidence suggests that the increased hydrostatic pressures in capillary beds, a hallmark of the early stages of insulin-dependent diabetes, are associated with macromolecular leakage leading to the typical thickening of glomerular capillary basement membrane and increased glomerular mesangial matrix even prior to the occurrence of systemic hypertension. Patients with renal or carotid artery stenosis seem to be protected against diabetic nephropathy and retinopathy on the stenosed side. The first signal of diabetic nephropathy even before deterioration of the renal function is microalbuminuria detected by sensitive methods such as radioimmunoassay. Not only in hypertensive, but even in normotensive diabetic patients with microalbuminuria antihypertensive therapy has been shown to reduce albumin excretion rate and to slow the progression of diabetic nephropathy. Once overt diabetic nephropathy has been established, hypertension is a constant accompaniment of the disease. Thus, hypertension may be a cause as well as a result of diabetic nephropathy. Tight control of blood sugar in close association with antihypertensive treatment reducing blood pressure to a lower normal limit, possibly with agents that specifically decrease glomerular capillary hydraulic pressure are the corner stone in protection against progression of the diabetic angiopathy.Abbreviations ECF
extracellular fluid
- ESRD
end-stage renal disease 相似文献
To characterize changes in serum cytokine levels in human immunodeficiency virus type 1 (HIV-1)-infected persons with Mycobacterium avium complex (MAC) bacteremia, the levels of IL-1alpha (interleukin-1alpha), IL-6, IL-10, tumor necrosis factor alpha (TNF-alpha), soluble type II TNF receptor (sTNF-RII), and transforming growth factor beta (TGF-beta) in serum were measured in two cohorts of HIV-1-infected persons with MAC bacteremia. The first cohort was part of a MAC prophylaxis study. Patients with bacteremia were matched with controls without bacteremia. Elevated IL-6, IL-10, TNF-alpha, sTNF-RII, and TGF-beta levels were noted at baseline for all subjects, a result consistent with advanced HIV-1 disease. IL-1alpha was not detected. No differences in cytokine levels in serum were noted at baseline and at the time of bacteremia between patients with MAC and controls. In the second cohort, subjects had serum samples collected at the time of MAC bacteremia and thereafter while on macrolide therapy. Serum samples at time of bacteremia were collected from HIV-1-infected persons at a time when neither highly active antiretroviral therapy (HAART) nor MAC prophylaxis was used routinely. MAC treatment resulted in decreased levels of IL-6 and TNF-alpha in serum, which were evident for IL-6 by 4 to 6 weeks and for TNF-alpha by 8 to 16 weeks. Thus, antibiotic treatment for MAC results in decreased levels of IL-6 and TNF-alpha in serum in HIV-1-infected persons who are not on HAART. 相似文献
Proximal tubules of the S1, S2 and S3 segments, medullary thick ascending limbs of Henle's loop (MAL) and cortical collecting tubules (CCT) were individually microdissected from rabbit kidneys and cultured for seven days in hormonally defined media. Anoxia was induced by incubation of cultures in normal medium for 45 min at 25 degrees C in an atmosphere of nitrogen (N2), and cell death was measured by nigrosine dye uptake. Immediately after anoxia, cell death was highest in S3 and MAL segments greater than S2 greater than S1 = CCT. The combined effects of anoxia and substrate (glucose, vitamins, amino acid) omission determined after incubation of cultures in phosphate buffered saline containing Ca2+ and Mg2+ (PBS) for 45 min in N2 also showed differential killing dependent on segment of origin: MAL greater than S3 greater than S2 CCT greater than S1. The effects of in vitro "reflow" were tested by returning cells to their normal oxygenated culture media at 37 degrees C. After the 45 min of anoxia and four to six hr of reflow in normal calcium-containing media, all cells from each segment were dead. Reflow in media lacking calcium for two hr immediately after anoxia then followed by return to normal calcium-containing media was associated with the survival of a significant percentage of cells for 48 hr: S1 (35.3 +/- 2.0%), S2 (30.0 +/- 2.0%), S3 (46.2 +/- 3.0%), MAL (38.7 +/- 3.0%), CCT (28.2 +/- 2.0%).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
Associations between social determinants of health (SDOH), demographic factors including preferred language, and SARS-CoV-2 detection are not clear. We conducted a retrospective cohort study among those seeking testing for SARS-CoV-2 at a multi-site, urban community health center. Logistic regression and exact matching methods were used to identify independent predictors of SARS-CoV-2 detection among demographic, SDOH, and neighborhood-level variables. Of 1,361 included individuals, SARS-CoV-2 was detected among 266 (19.5%). Logistic regression demonstrated that SARS-CoV-2 detection was less likely in White participants relative to Hispanic participants (adjusted odds ratio [aOR] 0.18, 95% confidence interval [CI] 0.05–0.46). and more likely in patients who prefer Spanish relative to those that prefer English (aOR 2.04, 95% CI 1.43–2.96). No observed SDOH predicted SARS-CoV-2 detection in adjusted models. A robustness analysis using a matched subset of the study sample produced findings similar to those in the main analysis. Preferring to receive care in Spanish is an independent predictor of SARS-CoV-2 detection in a community health center cohort.