Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of aminophylline on renal function in 10 premature infants with idiopathic apnea are evaluated. The percent increases in creatinine clearance (128 +/- 339%, mean +/- SD) and sodium clearance (196 +/- 304%, mean +/- SD) are variable while the percent increase in fractional sodium excretion (69 +/- 109%, mean +/- SD) is significant. This effect is postulated to be at the proximal tubule and may be modified by the effects of postnatal age and infusion of albumin. Gestational age, birth weight, heart disease, water and sodium intake and ventilatory support did not appear to influence the results. Hyponatremia is a potential consequence of theophylline therapy for apnea.
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PMID:The effects of theophylline on renal function in the premature newborn. 43 87

In order to examine the relation between cardiac state and the capacity to excrete a water load, 10 normal subjects and 61 patients with heart disease were studied during water diuresis. Under these conditions, urine flow approximates to the rate of delivery of filtrate, and therefore of sodium, from the proximal tubule of the kidney to the loop of Henle, while free water clearance is a function of distal sodium reabsorption. In 12 patients with complete heart block, ventricular pacing was associated with increased urine flow and free water clearance. Oral propranolol in 3 normal subjects and in 9 patients with intact atrial septa caused a reduction, and oral practolol in 4 normal subjects and 8 patients caused no change. In 6 patients with atrial septal defect, propranolol was without effect. Maximum urine flow correlated with left ventricular end-diastolic pressure but not mean left atrial pressure in 16 patients with chronic rheumatic heart disease. In 7 patients with ischaemic heart disease, maximum urine flow was higher than in those with chronic rheumatic heart disease and similar increase in left ventricular end-diastolic pressure. These results reflect a close relation between proximal tubular sodium reabsorption and cardiac state, and suggest that inappropriate sodium reabsorption at this site may contribute to fluid retention in heart disease.
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PMID:Assessment of proximal tubular sodium reabsorption during water diuresis in patients with heart disease. 439 57

Previous studies have demonstrated that the anesthetic amine, chlorpromazine hydrochloride (CPZ), prevents cell necrosis in experimentally induced ischemic liver and heart disease and decreases the extent of galactosamine-induced cell death in the liver. The present model was designed to determine whether CPZ exerts a similar beneficial effect in kidney in a nephrotoxic model of acute renal failure in rats induced by the administration of mercuric chloride (2 mg/kg of body weight). The functional and structural changes in the kidney were evaluated and quantitated in animals pretreated with CPZ (40 mg/kg of body weight) or saline and then subjected to nephrotoxic injury. Compared to controls, the glomerular filtration rate was significantly lower (p less than 0.001) in saline- and CPZ-pretreated rats receiving mercuric chloride. Twenty-four hours after mercuric chloride administration the glomerular filtration rate was 446 +/- 38 microl/minute/gm of kidney weight, the fractional sodium excretion was 0.4 +/- 0.2%, and the urinary osmolality was 1440 +/- 193 mOsmoles/kg of H2O in the CPZ-treated animals compared to 26 +/- 18 microl/minute/gm of kidney weight (p less than 0.001), 10.1 +/- 9.8% (p less than 0.025), and 353 +/- 28 mOsmoles/kg of H2O (p less than 0.005), respectively, in the animals receiving mercuric chloride alone. The percentage of proximal tubule cell necrosis was 26.5 +/- 8.9% in the CPZ-pretreated group compared to 88.1 +/- 3.6% in the untreated group (p less than 0.001). Metabolic cage studies were performed to follow the time course of this model for 48, 72, and 96 hours after mercury injection. The serum creatinine values and fractional sodium excretions were significantly less in animals receiving CPZ compared to the untreated group at all time intervals examined. The serum urea nitrogen concentration and glomerular filtration rate were similar for the two groups after 48 hours, but the serum urea nitrogen level was significantly lower and the glomerular filtration rate higher after 72 and 96 hours in the animals pretreated with CPZ. In agreement with these findings were observations that animals pretreated with CPZ had significantly fewer necrotic cells 48 and 72 hours after mercury administration, and tubular regeneration appeared to be markedly accelerated. These results suggest that pretreatment with CPZ markedly lessens the degree of structural and functional impairment seen in mercuric chloride-induced acute renal failure in rats and increases the rate of recovery.
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PMID:Partial protection by chlorpromazine in mercuric chloride-induced acute renal failure in rats. 623 24

The kidney is a major target organ for toxicity. Incidence of chronic kidney disease (CKD) is increasing at an alarming rate due to factors such as increasing population age and increased prevalence of heart disease and diabetes. There is a major effort ongoing to develop superior predictive models of renal injury and early renal biomarkers that can predict onset of CKD. In the EU FP7 funded project, Predict-IV, we investigated the human renal proximal tubule cells line, RPTEC/TERT1 for their applicability to long term nephrotoxic mechanistic studies. To this end, we used a tiered strategy to optimise dosing regimes for 9 nephrotoxins. Our final testing protocol utilised differentiated RPTEC/TERT1 cells cultured on filter inserts treated with compounds at both the apical and basolateral side, at concentrations not exceeding IC10, for 14 days in a 24 h repeat application. Transepithelial electrical resistance and supernatant lactate were measured over the duration of the experiments and genome wide transcriptomic profiles were assayed at day 1, 3 and 14. The effect of hypoxia was investigated for a subset of compounds. The transcriptomic data were analysed to investigate compound-specific effects, global responses and mechanistically informative signatures. In addition, several potential clinically useful renal injury biomarkers were identified.
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PMID:Application of RPTEC/TERT1 cells for investigation of repeat dose nephrotoxicity: A transcriptomic study. 2545 Jul 43