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Biomedical subjects

P Silva

Publications and source records attributed to P Silva.

At least 73 records · Page 4Linked to original sources
PubMed1993

Transport defects of rabbit medullary thick ascending limb cells in obstructive nephropathy.

To characterize the sodium transport defect responsible for salt wasting in obstructive nephropathy, the major sodium transporters in the medullary thick ascending limb (mTAL), the apical Na-K-2Cl cotransporter and the basolateral Na-K-ATPase, were studied in fresh suspensions of mTAL cells and outer medulla plasma membranes prepared from obstructed and untreated kidneys. Oxygen consumption (QO2) studies in intact cells revealed marked reductions in the inhibitory effects of both furosemide and ouabain on QO2 in cells from obstructed, as compared with control animals, indicating a reduction in activities of both the Na-K-2Cl cotransporter and the Na-K-ATPase. Saturable [3H]bumetanide binding was reduced in membranes isolated from obstructed kidneys, but the Kd for [3H]bumetanide was unchanged, indicating a decrease in the number of functional luminal Na-K-2Cl cotransporters in obstructed mTAL. Ouabain sensitive Na-K-ATPase activity in plasma membranes was also reduced, and immunoblots using specific monoclonal antibodies directed against the alpha and beta subunits of rabbit Na-K-ATPase showed decreased amounts of both subunits in outer medullas of obstructed kidney. A significant decrease in [3H]bumetanide binding was detected after 4 h of ureteral obstruction, whereas Na-K-ATPase activity at this time was still not different from control. We conclude that ureteral obstruction reduces the amounts of both luminal Na-K-2Cl cotransporter and basolateral Na-K-ATPase in mTAL of obstructed kidney and that these reductions contribute to the salt wasting observed after release of obstruction.

Animals↗
PubMed1993

[Dilated cardiomyopathy in a patient with Becker's muscular dystrophy. A clinical case report].

The authors report a case of dilated cardiomyopathy caused by a muscular dystrophy, namely Becker's disease. The peculiarity of this case is the fact that the patient has lived enough time to have clinical manifestations of myocardiopathy because, in general, in this myopathy, the affected males have a short life and the early myocardial involvement is rare. A particular attention is paid to the need of consulting the cardiac patients not forgetting an eventual causal systemic disease and to the crucial importance of the genetic counselling in that kind of diseases.

Adult↗
PubMed1992

The effect of mercury on chloride secretion in the shark (Squalus acanthias) rectal gland.

1. Mercuric chloride inhibited chloride secretion in a dose dependent way in isolated perfused rectal glands. The effect was readily apparent at a concentration of 10(-6) M and profound and irreversible at 10(-4) M. 2. The dithiol dithiothreitol (DTT) 10(-2) M completely prevented the effect of 10(-6) M mercuric chloride, reduced that at 10(-5) M and 10(-4) M, and made the inhibition at the latter concentration reversible. 3. Two organic mercurials, mersalyl and meralluride, that are effective diuretics in the mammalian kidney, and p-chloromercuribenzoyl sulfonic acid (PCMBS), that has no diuretic activity, had no effect on chloride secretion by the rectal gland. 4. The effect of mersalyl was not modified by lowering the pH of the solution perfusing the glands. 5. These results indicate that inorganic mercury and organic mercurials do not share the same mechanism of action. 6. The absence of an effect of organic mercurials on chloride transport in the rectal gland suggests that its effect on another chloride transporting epithelia, the thick ascending limb of the loop of Henle, is not mediated by inhibition of the chloride cotransporter or Na+, K(+)-ATPase, common to both epithelia.

4-Chloromercuribenzenesulfonate↗
PubMed1992

C-type natriuretic peptides stimulate chloride secretion in the rectal gland of Squalus acanthias.

Homologous shark C-type natriuretic peptide (sCNP) was infused as a bolus and as a constant infusion in the isolated perfused rectal gland of the same species, Squalus acanthias. sCNP was a potent stimulator of chloride secretion similar in its dose-response curve to vasoactive intestinal peptide. sCNP was equipotent with killifish CNP but more potent than human CNP (hCNP). Truncated and substituted, forms of hCNP were also capable of stimulation of chloride secretion in the order hCNP greater than hCNP (6-22) = [Gly9]hCNP greater than hCNP-(7-21). sCNP was more potent than human atrial natriuretic peptide (hANP), which was more potent than porcine brain natriuretic peptide. hANP-(31-67) was without effect. These studies suggest that sCNP may be the physiological regulator of rectal gland function. The receptor in the rectal gland is unknown but based on the order of potencies, position 4 in the NH2-terminal end and the ring itself are important for ligand effects.

Amino Acid Sequence↗
PubMed1992

cAMP activates the sodium pump in cultured cells of the elasmobranch rectal gland.

The inorganic ion content of rectal gland cells cultured from Squalus acanthias was studied by electron probe analysis in order to determine the effect of stimulation by cAMP. Cell sodium was reduced by 30% (P less than 0.01) at 8 min after exposure to dibutyryl cAMP and theophylline and remained low at 25 and 33 min. Chloride content also fell significantly with stimulation. Although cAMP may activate several transport sites, the results are consistent with a direct effect of stimulation to increase the activity of the sodium pump in shark rectal gland.

Animals↗
PubMed1991

Toxicity of adenine nucleotides in the isolated perfused kidney: selective destruction of the S2 segment of the proximal tubule.

In an attempt to ameliorate the morphological abnormalities and decreased renal function produced by hypoxia in the isolated perfused rat kidney, adenosine triphosphate (ATP) was added to the perfusate medium. No improvement was noted in the histological changes or renal function. Paradoxically, however, in oxygenated control kidneys, ATP (2.5-10 mM), caused a severe injury remarkably limited to the S2 segments of proximal tubule. This injury was more destructive than that observed with complete ischemia for the same period of time or with inhibitors of glycolysis, intermediary metabolism, or respiratory chain function. Tubular damage produced by ATP was paradoxically prevented by hypoxia and mitochondrial inhibition. The mechanism of this selective toxic injury to the proximal tubule remains unclear and may depend upon intact transport metabolism of the cell.

Adenosine Diphosphate↗
PubMed1991

Protective action of glycine in cisplatin nephrotoxicity.

Because glycine is cytoprotective for kidney cells in vitro, we investigated its possible action in vivo to protect rats against cisplatin nephrotoxicity, a well-established experimental model of renal tubular injury. Glycine was infused at a dose of 1 mmol per 100 g body weight per hour for 75 minutes, starting 15 minutes before cisplatin, 5 mg per kg, was injected intravenously. Plasma concentration of glycine rose to 3.5 mmol per liter at the time cisplatin was injected. These rats were compared with cisplatin-treated animals treated with L-alanine or with isotonic saline. After five days plasma creatinine of saline-treated rats given cisplatin had risen threefold to 2.6 +/- 1.5 mg per 100 ml (mean +/- SD), as creatinine clearance fell to 25% of baseline (0.14 +/- 0.05 ml/min/100 g). Morphological evaluation disclosed extensive damage involving all S3 segments in the outer medulla as well as the medullary rays of the cortex. In contrast, in rats treated with glycine, plasma creatinine rose only to 1.2 +/- 0.2 mg/100 ml and creatinine clearance was maintained at 75% of baseline (0.35 +/- 0.05 ml/min/100 g). Glycine also attenuated the weight loss, polyuria, increased fractional excretion of sodium and potassium, decreased urinary osmolality, and renal glycosuria observed in control, saline-treated rats after cisplatin, while substantially decreasing the percentage of S3 tubules with evident morphological injury. Renal platinum content was unaffected by glycine. The administration of L-alanine or the delayed infusion of glycine, starting one hour after cisplatin was given, did not prevent cisplatin toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Early renal medullary hypoxic injury from radiocontrast and indomethacin.

We evaluated the acute changes in cortical and outer medullary oxygen tension and the alterations in renal function and morphology within the first 90 minutes after the administration of indomethacin and iothalamate to anesthetized Sprague-Dawley rats. Both agents were found to produce marked and protracted outer medullary hypoxia averaging 12 +/- 4 and 9 +/- 2 mm Hg, respectively (mean +/- SE). Given together to salt depleted uninephrectomized rats they produced an early hypoxic injury localized selectively in the outer medulla. This lesion progressed from 3 +/- 1% of medullary thick ascending limbs (mTALs) at 15 minutes to 22 +/- 7% at 24 hours. Condensed "dark" cells were observed at 15 minutes, probably representing a type of early injury. Residual red cell mass, quantified in the outer medullary vasculature of perfusion-fixed kidneys and presumably reflecting stasis, was substantially increased in iothalamate treated rats. Red cell mass in the interbundle zone correlated with mTAL necrosis. Taken together, these results show an early period of medullary hypoxia, accompanied by a selective injury to mTALs in the central interbundle zone with apparent stasis. These findings contrast sharply with the ischemia-reflow pattern of renal damage and emphasize the important role of medullary hypoxia in the genesis of acute renal failure in this model.

Animals↗
PubMed1991

Effect of glycine on medullary thick ascending limb injury in perfused kidneys.

The addition of 2 mM glycine to the recirculating perfusate of isolated perfused rat kidneys almost completely prevented the severe morphological injury to tubular cells lining the medullary thick ascending limb (mTAL) that normally develops in this preparation. Glycine was similarly effective in reducing mTAL injury associated with hypoxic perfusion, indomethacin and amphotericin. Fractional reabsorption of sodium was increased with glycine, without any change in perfusate flow to the whole kidney and without consistent improvement in GFR. L-alanine demonstrated a similar though less pronounced cytoprotective action, but glutamine, cysteine, glutamate, cysteine plus glutamate, 1-serine and 4-aminoisobutyric acid all had little or no effect in preventing severe mTAL injury. The protective effect of glycine was unimpaired by the arginine analogue NG-monomethyl-l-arginine (L-NMMA), suggesting that the endothelial-derived relaxing factor, NO, was not involved. The action of glycine was not reduced by the addition of a substrate (benzoate) or a product (hippurate) of the glycine N-acyltransferase reaction. Glycine did not depress the respiration of dispersed mTALs prepared from rat kidneys. The cytoprotective effect of glycine in the mTAL of perfused kidneys, shared with l-alanine, appears to be relatively specific for these amino acids and probably unrelated to a diminution in cell work.

Amino Acids↗
PubMed1991

A longitudinal study of New Zealand children's experience with alcohol.

A longitudinal study assessed the use of alcohol and related measures among New Zealand children aged 9, 11, 13 and 15 years. The proportion of children who were abstainers was at a similar level to the adult population by age 15 years. Those remaining abstainers were more likely to have infrequently drinking parents and to have been warned of the bad effects of alcohol by their parents. In terms of amount consumed and frequency of drinking, there was an increase with age and a marked increase between the ages of 13 and 15 years. Frequency of drinking was positively associated with the frequency of drinking by the mother and father. Girls drank less than boys until the age of 15 years, when they drank slightly more and a difference in terms of socio-economic status (SES) emerged at age 15 years with lower SES groups drinking more.

Alcohol Drinking↗
PubMed1991

Isolated MTAL cells produce an inhibitor of ouabain-sensitive oxygen consumption.

Dispersed medullary thick ascending limb (MTAL) cells of the rabbit kidney produce an inhibitor of transport-related oxygen consumption when incubated at 37 degrees C. Appearance of this inhibitor is enhanced by incubation with arachidonic acid. Its appearance can be prevented by either 10(-6) M nordihydroguaiaretic acid or 10(-4) M indomethacin, but not by 10(-6) M indomethacin. These results suggest that the transport inhibitor is an eicosanoid produced by a pathway other than that catalyzed by cyclooxygenase. It inhibits ouabain-sensitive respiration in intact cells treated with amphotericin, suggesting direct inhibition of the Na(+)-K(+)-ATPase.

Amphotericin B↗
PubMed1991

Renal artery imaging: a prospective comparison of intra-arterial digital subtraction angiography with conventional angiography.

This study describes a systematic comparison of intra-arterial digital subtraction angiography (DSA) of the main renal arteries with conventional angiography (CA), the currently accepted "gold standard" for the diagnosis of renal artery stenosis. Twenty-five patients scheduled for abdominal aortography for various indications underwent first DSA then CA. The DSA and CA images were evaluated for number of renal arteries, presence and grade of renal artery stenosis, presence of post-stenotic dilation or fibromuscular changes, and diagnostic and pictorial adequacy of the images. DSA was found to be diagnostically adequate in 92% of cases, compared with 96% for CA. In evaluating significant main renal artery stenosis, which the authors assumed to be any stenosis greater than 50%, there were 10 such stenoses seen by CA. DSA also detected 10 cases, but there was 1 false positive and 1 false negative, yielding a sensitivity of 90% and a specificity of 98%. There was also close correlation of DSA and CA for the few cases of post-stenotic dilatation and fibromuscular dysplasia encountered. The authors conclude that DSA is an acceptable substitute for CA in the evaluation of patients for main renal artery stenosis.

Angiography↗
PubMed1990

Effect of myo-inositol on renal Na-K-ATPase in experimental diabetes.

The activity of Na-K-ATPase in the kidney is increased by experimental diabetes. Because the kidney is rich in myo-inositol and abnormal inositol metabolism has been implicated in early neural complications of diabetes, we studied the effect of myo-inositol supplementation on Na-K-ATPase activity in renal medullary and cortical homogenates of Sprague-Dawley rats made diabetic with streptozotocin. Myo-inositol (650 mg/kg) was administered by gavage daily for 1 and 2 weeks after induction of diabetes. Medullary Na-K-ATPase (mumol/mg protein/h) was increased at 1 week by approximately 60% in diabetic rats versus control (25.9 +/- 0.07 vs 16.3 +/- 0.7; P less than .01). This increase was completely prevented by myo-inositol supplementation, despite persistent hyperglycemia. At 2 weeks, similar results were seen; medullary Na-K-ATPase activity was increased by 50% in diabetic rats compared with control, and once again myo-inositol prevented this increase. Sorbinil, the aldose reductase inhibitor, was also administered by gavage (20 mg/kg) for 2 weeks and partially prevented the increase in medullary Na-K-ATPase activity (20.0 +/- 0.9; P less than .05). At both 7 and 14 days, Na-K-ATPase activity in the cortex of untreated diabetic rats was also significantly increased compared with nondiabetic control rats and the increase was prevented by myo-inositol or Sorbinil. Myo-inositol or Sorbinil did not reduce Na-K-ATPase activity of nondiabetic control rats, nor did they prevent the increase in medullary Na-K-ATPase in compensatory hypertrophy following uninephrectomy. Myo-inositol content of outer medulla was about five to six times that of cortex, but was unaltered by the diabetic state.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

The weight control practices of 15 year old New Zealanders.

More than 800 15 year old members of the Dunedin Multidisciplinary Health and Development study cohort completed a questionnaire designed to provide descriptive data concerning the weight control behaviours of this sample of New Zealand adolescents. The results showed that approximately 75% of the adolescents were within acceptable body mass index ranges. However 68% of the girls (but only 19% of the boys) wanted to weigh less than their present weight. Generally, girls were more concerned about their body weight than boys: 26% of girls weighed themselves fortnightly or more often, compared with 12% of boys; 45% of girls reported that they were trying to lose weight at present, compared with 9.5% of boys. The main methods of weight reduction included weight reduction diets (21% of girls, 4% of boys in the previous year); exercise such as jogging, walking, swimming and cycling (60% of girls, 34% of boys); and participation in dieting and fitness clubs (35% of girls, 16% of boys). In addition, 20% of girls reported using techniques such as slimming tablets (3%), cigarette smoking (5%) and self-induced vomiting (5%) to control weight. The results show that weight control is a major preoccupation of many girls and some boys. Results are discussed in relation to differential social influences on the sexes, and health consequences.

Adolescent↗