Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0231807 (exertional dyspnea)
 3,402 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The rate of neonatal proximal convoluted tubule (PCT) HCO3 absorption is lower than that of adult animals. The present in vitro microperfusion study examined whether prenatal dexamethasone (60 micrograms/kg daily to the doe for 3 days before delivery) would accelerate the maturation of neonatal juxtamedullary PCT acidification. Control neonates studied within 48 h of birth had a urine pH of 7.06 +/- 0.15 and a urine HCO3 concentration of 34.3 +/- 7.0 meq/l. Animals receiving dexamethasone had a urine pH of 6.47 +/- 0.11 and a urine HCO3 concentration of 10.1 +/- 4.0 meq/l, both of which were significantly lower than control (P less than 0.01). In juxtamedullary PCTs perfused in vitro, volume absorption was 0.27 +/- 0.03 nl.mm-1.min-1 in controls and 0.39 +/- 0.02 nl.mm-1.min-1 in dexamethasone-treated animals (P less than 0.05). HCO3 absorption was stimulated in the dexamethasone group (52.6 +/- 4.6 vs. 34.1 +/- 6.3 pmol.mm-1.min-1, P less than 0.05); however, glucose transport was not significantly affected (24.8 +/- 1.3 in dexamethasone vs. 21.5 +/- 3.5 pmol.mm-1.min-1 in controls). Intracellular pH was measured using 2',7'-bis(carboxyethyl)-5(6)-carboxyflourescin to examine whether prenatal dexamethasone stimulated the apical Na(+)-H+ antiporter and the basolateral Na(HCO3)3 symporter. Apical Na(+)-H+ antiporter proton flux was 108.5 +/- 14.2 pmol.mm-1.min-1 in the control group and 250.7 +/- 31.3 pmol.mm-1.min-1 in the dexamethasone group (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prenatal glucocorticoids stimulate neonatal juxtamedullary proximal convoluted tubule acidification. 195 7

We have recently demonstrated that intramuscular administration of triiodothyronine (T3) or thyroxine (T4) to the rabbit doe results in its transfer across the placenta. In this study we investigated the effect of maternally administered T3 upon the functional and morphologic fetal lung maturation. T3 (175 micrograms/kg) or the vehicle was injected intramuscularly into the New Zealand White rabbit does on days 25 and 26 of gestation. On day 27 of pregnancy, the does were killed and the fetuses were delivered. Maternal and fetal plasma T3, glucose and insulin and fetal plasma corticosteroid concentrations were determined. The functional pulmonary maturity was assessed by performing the pressure-volume hysteresis while morphologic maturity was established by histologic techniques. Enhanced functional as well as morphologic fetal lung maturation was observed in female as well as male fetuses in T3-treated animals. However, there was a significant increase in the fetal mortality after T3 treatment, and the duration of survival in the extrauterine environment on premature delivery was not prolonged.
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PMID:Transplacental stimulation of fetal lung maturation: effect of triiodothyronine in the female and male rabbit fetus. 365 23

Although rabbit has been used as a convenient animal model in understanding the role of thyroid hormones during the perinatal development, ontogenetic changes in plasma-free thyroxine or triiodothyronine concentration has not been studied in this species. We delineated the ontogeny of immunoreactive plasma-free thyroxine and triiodothyronine concentration during the perinatal period. It is generally believed that thyroid hormones do not cross the placenta from the mother to the fetus in sufficient concentrations to exert biological effects in the fetus. We administered 250 micrograms/kg of thyroxine (T4) or 125 micrograms/kg of triiodothyronine (T3) intramuscularly to the rabbit doe on the 25th and 26th day of gestation. Maternal and fetal plasma-free T4, T3 and glucose concentration and fetal liver glycogen content were quantitated on the 27th day of gestation. Maternal and fetal plasma-free T4 and T3 concentration was significantly higher than the control in T4-treated animals. Maternal and fetal plasma T3 concentration was higher and free T4 concentration lower than the control in T3-treated animals. T3 or T4 treatment resulted in fetal hyperglycemia and depletion of fetal hepatic glycogen content. We conclude that T4 or T3 cross the rabbit placenta and exert thyromimetic effects in the fetus. A convenient animal model to investigate in utero effects of T4 or T3 in mammalian fetal development is proposed.
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PMID:Ontogeny of plasma-free thyroxine and triiodothyronine concentrations during the perinatal period and maternofetal transfer of thyroid hormones in the rabbit. 395 45

1. The concentration of blood glucose, free fatty acids and serum glycerol of the doe, new-born and young rabbits have been measured in order to evaluate the effects of age, starvation and environmental temperature on the circulating concentrations of these metabolites.2. The blood glucose, free fatty acid and glycerol concentrations were lower in the new-born than in the mother rabbit.3. Starvation for 24 hr of new-born and young rabbits in a thermal neutral environment did not alter the serum free fatty acid or glycerol concentrations. The blood glucose of unfed rabbits fell during the first 24 hr of life.4. Cold exposure (15 or 25 degrees C) for 1 hr caused a rise in the concentration of blood glucose, serum free fatty acids and glycerol.5. When the metabolic response of new-born and young rabbits to cold exposure was measured, it was found that there was a direct correlation between the serum glycerol concentration and the metabolic response. The greatest rise in the serum free fatty acids occurred in the blood of rabbits with the poorest metabolic response to cold.6. It is suggested that in the steady state during cold exposure the serum glycerol concentration may indicate the rate of triglyceride hydrolysis in brown adipose tissue.
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PMID:The effects of age and environmental temperature on the blood concentrations of glucose, free fatty acids and glycerol in new-born rabbits. 576 89

The benefit of any medical intervention, particularly drug therapy, must be weighed against its cost. These costs are not only dollar expenditures but effects on lifestyle and overall health. Diuretic therapy for hypertension has been in use long enough to allow long-term clinical evaluation. It is clear from the numerous prospective drug intervention trials involving hypertensive patients that diuretic therapy is not free of "costs." Aside from the fact that 15 to 20% of diuretic-treated patients reportedly drop out of trials because of side effects, including exertional dyspnea, fatigability, lethargy and impotence, numerous metabolic derangements have been reported with these drugs, i.e., potassium, uric acid, lipid, sodium, glucose and magnesium alterations. Perhaps most important are the changes in lipid fractions, which may be responsible for the failure of antihypertensive therapy to decrease the risk of coronary heart disease. Thus, although diuretics are somewhat less expensive than other antihypertensive drugs in terms of dollars, their overall costs are high. The major alternatives, such as the alpha-blocker prazosin or the central nervous system agent clonidine, are preferable, do not impair a patient's lifestyle and are recommended to be used along with changes in diet and an exercise program for control of mild to moderate hypertension.
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PMID:Diuretic therapy for mild hypertension: the "real" cost of treatment. 642 Nov 37

In the present investigation, myo-inositol was elevated in fetal serum by dietary manipulation. The myo-inositol-containing diet doubled the already high fetal serum myo-inositol between fetal days 26 and 28 but had no detectable effects on the lung. However, myo-inositol decreased betamethasone-induced (0.2 mg/kg, days 26.3 and 27.3, to the doe) inhibition in lung growth and potentiated the hormone-induced increase in alveolar space saturated phosphatidylcholine. This effect could not be explained by alteration of glucocorticoid-stimulated enzyme activity (phosphatidate cytidylyltransferase, phosphatidic acid phosphohydrolase, choline phosphate cytidylyltransferase) in the lung. Lung explants from 26-day-old fetuses were grown in a serum-free medium for 4 days. myo-Inositol (1.5 mM) had only a small effect on the phospholipid incorporation. Dexamethasone and thyroxine increased the incorporation of the precursors into surfactant phosphatidylglycerol and saturated phosphatidylcholine. myo-Inositol, in the presence of the hormones, switched the acidic surfactant phospholipid from phosphatidylglycerol to phosphatidylinositol and further increased the incorporation of surfactant-associated saturated phosphatidylcholine. myo-Inositol-excess preferentially increased the incorporation of NADPH (derived from glucose) and acetate into the fatty acid moiety of surfactant phosphatidylcholine. It is proposed that the high extracellular myo-inositol in immature fetuses provides an environment that promotes both the hormone-stimulated differentiation and the growth.
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PMID:Effect of extracellular myo-inositol on surfactant phospholipid synthesis in the fetal rabbit lung. 654 57

In the present study we investigated the maturation of the surfactant phospholipids and the role of fetal sex on the effect of betamethasone in male and female rabbit fetuses. Betamethasone was administered to the doe (0.2 mg/kg intramuscularly) 42 and 18 h prior to killing. The fetuses were studied at 27 and 28 days from conception. Results from the alveolar lavage show that male fetuses tended to have a lower disaturated phosphatidylcholine/sphingomyelin ratio and lower levels of phosphatidylinositol. Phosphatidylglycerol was detected in trace amounts. This was apparently due to the high extracellular levels of myo-inositol inhibiting the synthesis of surfactant phosphatidylglycerol while increasing the synthesis of surfactant phosphatidylinositol. Betamethasone increased the recovery of disaturated phosphatidylcholine and phosphatidylinositol from the lung lavage in both sexes. As studied in lung slices in vitro, the betamethasone treatment decreased the incorporation of glucose into phospholipids, including into the fatty acid moiety of disaturated phosphatidylcholine, although it had no significant effect on the incorporation of glucose into the glycerol moiety of disaturated phosphatidylcholine. However, the addition of palmitate increased the incorporation of glucose into the glycerol moiety of disaturated phosphatidylcholine. The betamethasone treatment did not increase the incorporation of [1-14C]pyruvate into disaturated phosphatidylcholine. Following betamethasone administration, the availability of fatty acids may become rate-limiting for the synthesis of surfactant phospholipids. Betamethasone increased the activities of phosphatidic acid phosphohydrolase and phosphatidate cytidyltransferase in a fraction of microsomal membranes. The present evidence suggests that the glucocorticoid-induced lung maturation and the maturation of the normal lung are associated with an increase in the activity of the enzymes which are involved in metabolizing phosphatidic acid to neutral and acidic surfactant secretion of the male fetus was not explained by possible sex-related differences in the biosynthesis of the phospholipids.
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PMID:The effect of betamethasone and fetal sex on the synthesis and maturation of lung surfactant phospholipids in rabbits. 682 16

Atenolol, a cardioselective beta-adrenergic blocking agent, was given as the sole hypotensive drug for 8-12 weeks to 20 patients with hypertension of varying degrees of severity. Initial systolic blood pressure ranged from 162-238 mm Hg (mean +/- SEM 196 +/- 5.5 mm Hg) and diastolic blood pressure ranged from 105-143 mm Hg (118 +/- 2.5 mm Hg). Three patients had accelerated hypertension, six had cardiomegaly with recent exertional dyspnea and three were diabetics. Atenolol, 100-300 mg once daily, controlled both the supine and standing blood pressure and markedly attenuated the initial hypertensive response to severe exercise. In 17 patients (85%), atenolol therapy reduced blood pressure more than 20/10 mm Hg; however, adequate blood pressure control was not achieved in severe hypertension. A significant hypotensive action developed within 2 weeks of treatment, and control of hypertension was maintained for 2 weeks after sudden interruption of therapy. No patient had postural or postexercise hypotension. The drug appeared to exert its maximum hypotensive effect at the 100-mg dosage. The magnitude of the hypotensive response was related to the initial systolic blood pressure (r = 0.77, p less than 0.01) and the degree of inhibition of exercise tachycardia (r = 0.66, p less than 0.01). The atenolol plasma level and its hypotensive action were not related. Except for impairment of glucose tolerance in diabetic patients, atenolol had minimal side effects.
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PMID:Clinical evaluation of atenolol in hypertensive patients. 724 4

Although the benefit of angiotensin converting enzyme (ACE) inhibitors in diabetic nephropathy is well documented in double-blind randomized, controlled clinical trials, it is uncertain whether the benefit extends to unselected patients with diabetes mellitus and arterial hypertension in general practice. In 2504 unselected patients with type 2 diabetes mellitus (mean age 63+/-10 years) blood pressure, cardiovascular, renal, and metabolic parameters were assessed at baseline and during a treatment period of 1 year with the ACE inhibitor cilazapril by primary care physicians. The average dose of cilazapril was 2.5 mg/day. Outcome measures were blood pressure, serum creatinine, proteinuria (dip stick), HbA1c levels, evaluation of edema, and exertional dyspnea. In the study cohort, systolic blood pressure decreased by 24+/-17 mm Hg and diastolic blood pressure by 12+/-11 mm Hg. An increase in serum creatinine (> 0.2 mg/dL) occurred more frequently in patients with than in those without renal involvement (19% v 7%; P < .05). Serum creatinine decreased more frequently in patients with renal involvement than in those without (26%+/-4% v 12%+/-3.8%; P < .05). Overall renal function in patients with diabetic nephropathy (n = 318) improved (2.1+/-1.6 mg/dL v 1.7+/-1.4 mg/dL; P < .05). The frequency of proteinuria was lower after 1 year than at baseline (62%+/-9% v 82%+/-8%; P < .05). Metabolic control of diabetes mellitus improved in parallel (median HbA1c 8.0% v 7.0%; P < .01). Scores for edema formation and exertional dyspnea improved as well (P < .01). In this outcome survey of unselected patients with type 2 diabetes mellitus and arterial hypertension, the ACE inhibitor cilazapril effectively lowered blood pressure, which was associated with an improvement in glucose metabolism, cardiac function, and renal function.
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PMID:Outcome survey in unselected hypertensive patients with type 2 diabetes mellitus: effects of ACE inhibition. 1146 52

Among nutrients, the role of water-soluble vitamins as genetic expression modulators has not been exhaustively stu-died. Relevant information is shown herein on the present state of the art in this field. For example, vitamin C deficiency leads to a decrease in mRNA levels of apolipoprotein A1 (Apo A1) in liver. Biotin participates in the regulation, both at mRNA and protein level, of the enzymes that participate in its own metabolic cycle and of enzymes that contribute to glucose metabolism. Thiamine regulates the expression of some genes that code for enzymes using thiamine diphosphate as cofactor. Thiamine deficiency diminishes the mRNA levels of transketolase and pyruvate dehydrogenase. It has been shown in riboflavin-deficient rats that FAD regulates some acetyl CoA dehydrogenases, producing a marked increase in mRNA levels. Nicotinamide positively regulates glyceraldehyde-3-phosphate dehydrogenase when NADH is added. Vitamin B6 modulates the expression of a variety of genes that respond to hormones. Vitamin B12 increases concentrations of the enzymatic protein methionine synthetase and doe not affect mRNA levels, which implies that this protein is regulated by its cofactor post-transcriptionally. Most mechanisms involved in these regulation examples are not known, which opens new research areas for the future.
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PMID:[Importance of water-soluble vitamins as regulatory factors of genetic expression]. 1199 11


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