Nephron segment and calcium as determinants of anoxic cell death in renal cultures

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)     

Social Determinants and COVID-19 in a Community Health Center Cohort

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.

     

Therapy of heart failure

The incidence and prevalence of heart failure is on the rise. It has become the single most expensive health care item in the United States and the number one discharge diagnosis in the elderly. The goals of therapy include both prevention and treatment of heart failure. In recent years research studies and randomized clinical trials have revolutionized the understanding of the pathophysiology and treatment of this disease. This article focuses on the medical management of chronic systolic heart failure based on the pathophysiology of the disease. Systolic heart failure is characterized by a decrease in left ventricular function and cardiac output, which results in activation of several neurohormonal compensatory systems. The long term effects of this neurohormonal activation leads to further deterioration of cardiac function. The use of hydralazine and nitrates to reduce the systemic vascular resistance was the first to show an improvement in mortality and morbidity. Then angiotensin converting enzyme inhibitors, by inhibiting the renin angiotensin system, demonstrated a greater improvement in mortality and morbidity. More recently the inhibition of the sympathetic stimulation with beta-blockers has been shown to have an additive effect on morbidity and mortality in combination with angiotensin-converting enzyme inhibitors. Digoxin and diuretics remain important for improving symptoms and decreasing hospitalizations but have not been shown to decrease mortality. The most recent advance in the treatment of cardiac failure is the demonstration that the aldosterone antagonists, spironolactone decreases morbidity and mortality.     

Cardiorenal Syndrome: Pathophysiology and Treatment

The coexistence of an acute coronary syndrome (ACS) and non-cardiac surgery (NCS) in an individual patient can be summarized in two challenging clinical scenarios for the treating physician: 1) Post-operative patients who develop ACS and 2) Patients with ACS who subsequently require NCS. Both settings are characterized by a struggle on the part of treating physicians attempting to optimize antithrombotic therapies for ACS while minimizing post-surgical bleeding risk. In this review we address specific clinical issues related to patients with coexistent NCS and ACS, discussing possible management strategies balancing ischemic and bleeding risk in these complex patient scenarios.     

Differential effects of antihypertensive agents on electrocardiographic voltage: results from the Appropriate Blood Pressure Control in Diabetes (ABCD) trial

Background

Serial decline in electrocardiographic voltage in patients with increased left ventricular mass has been associated with a lower risk of cardiovascular events.

Methods

We studied 468 patients with diabetes mellitus and hypertension in the Appropriate Blood Pressure Control in Diabetes (ABCD) trial. Patients were randomized in a stratified design to receive initial treatment with either enalapril or nisoldipine and to either intensive or moderate treatment goals. We measured an electrocardiographic index for increased left ventricular mass, the adjusted Cornell voltage, serially by treatment group. The association between changes in electrocardiographic voltage and cardiovascular events was defined with Cox proportional hazards analysis.

Results

In 5 years of follow-up, the decline in adjusted Cornell voltage was significantly greater for patients treated with enalapril than for patients treated with nisoldipine (repeated measures analysis of variance P = .002). In the Cox proportional hazards model, treatment assignment (enalapril vs nisoldipine) was the strongest predictor of cardiovascular events, but the presence of coronary disease at baseline, the duration of diabetes mellitus, and change in voltage were also independent predictors of cardiovascular events.

Conclusions

In the ABCD study, enalapril treatment was associated with a lower risk of myocardial infarction. The reduction in left ventricular mass as reflected by diminished electrocardiographic voltage may explain some, but not all, of the effect of enalapril in this study.     

Albuminuria as a predictor of heart failure hospitalizations in patients with type 2 diabetes

BACKGROUND: Heart failure (HF) occurs more frequently and is a significant cause of mortality in diabetic patients. The purpose of the current study is to ascertain risk factors that are predictive of HF hospitalizations in type 2 diabetic patients. METHODS: Longitudinal observational study of type 2 diabetic patients with baseline diastolic blood pressures > or =80 mm Hg and no history of New York Heart Association class III-IV HF or a serum creatinine > or =2.5 mg/dL nested within a randomized clinical trial. The outcome measure of this study was the first occurrence of HF hospitalization over a 5-year follow-up period. RESULTS: Patients with overt albuminuria at baseline had a higher and earlier occurrence of HF hospitalizations than those with micro- or normoalbuminuria (13.6% versus 3.3%, odds ratio [OR]=3.1, 95% confidence interval [CI]=2.15-4.60, P<.0001). In the multiple logistic regression analyses, the presence of overt albuminuria (OR 5.4, 95% CI=2.3-12.5, P<.001), history of myocardial infarction (OR 4.6, 95% CI=1.6-13.1, P=.004) and a history of New York Heart Association Class I or II HF (OR 8.0, 95% CI=2.2-28.6, P=.0014) at baseline were independently associated with HF hospitalizations. CONCLUSIONS: Overt albuminuria predicts the occurrence of HF hospitalizations in type 2 diabetic patients. Thus early aggressive treatment of diabetic nephropathy should be investigated as a means of preventing of HF.     

The effects of the nude (nu/nu) mutation on bleomycin-induced pulmonary fibrosis. A biochemical evaluation

Previous reports have suggested that the immune system is involved in the lung fibrogenic response to certain agents or treatments. In the present study, we have evaluated the impact of the athymic (nude) mutation on the development of pulmonary fibrosis in mice induced by a single intratracheal instillation of bleomycin (0.75 units/animal). Histologic examination revealed that cellular infiltration, fibroblast proliferation, and connective tissue accumulation were diminished in the nude mice when compared with euthymic (het) control mice. In contrast to control animals treated with saline, total lung hydroxyproline in the nude mouse was not significantly increased at 14 and 30 days after bleomycin treatment. Net collagen synthesis, as assessed by measuring the rate of incorporation of tritiated proline in an organ culture system, was increased above control values in both nude and euthymic mice at 14 days after bleomycin treatment, although these values returned to normal at 30 days. However, lung collagen synthetic rates, normalized to dry lung weights, were significantly higher at 14 days in euthymic bleomycin-treated control mice than in the nude bleomycin-treated animals. The data indicate that the nude athymic mutation protects, at least partially, against bleomycin-induced pulmonary fibrosis, thus suggesting a role for the cellular immune system in regulating the fibrogenic response to this drug.