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Biomedical subjects

A Aperia

Publications and source records attributed to A Aperia.

At least 145 records · Page 8Linked to original sources

Paralytic ileus, a serious complication in acute diarrhoea disease among infants in developing countries.

Intestinal hypomotility is a common late complication in infants with acute diarrhoeal disease in pakistan. Among the infants admitted to our gastrointestinal unit with a history of acute diarrhoea, 35% developed abdominal distension and 12% developed the full clinical picture of paralytic ileus. The infants with ileus were treated with decompression and total parenteral nutrition; in this group the mortality rate was 25%. We compared 30 infants who developed ileus (group A) with an age-matched control group of infants (group B) who were admitted because of acute diarrhoea but did not develope ileus. The use of antimotility drugs was significantly more frequent in group A. Serum-K was not different in in group A (3.92 +/- 0.22 mmol/l) and group B (4.32 +/- 0.18 mmol/1). However, there were more patients who had serum-K below 3 mmol/l in group A (8/30) than in group B (5/30). We conclude that the use of antimotility drugs predisposes to the development of ileus in infants with acute diarrhoea. Hypokalemia may contribute to ileus in a few cases but is generally not a prerequisite.

Acute Disease↗

Renal function in different forms of renovascular hypertension in rats.

This study examines renal function in different rat models of renovascular hypertension. Hypertension was induced by constriction of the aorta proximal to the renal artery (PAC), by PAC and nephrectomy (PAC + Nx) or by renal artery stenosis (RAS). PAC + Nx is equivalent to the Goldblatt 1 kidney-I clip hypertension model. The PAC rats were studied 3 weeks after surgery. Hypertension was by then well established. GFR, measured as the clearance of inulin, was significantly lower in PAC rats than in control (C) rats. GFR was the same in PAC + Nx rats as in C rats, but significantly lower in PAC + Nx than in Nx rats. Kidney weight was significantly higher in PAC + Nx rats than in C rats. Filtration fraction (FF), measured as the ratio between GFR and the clearance of PAH, was significantly higher in PAC and PAC + Nx rats than in C and Nx rats. In RAS rats hypertension was not established until 6 weeks after surgery, and RAS is equivalent to Goldblatt 2 kidney-I clip hypertension. Renal artery constriction was moderate as judged from the weight ratio between the stenosed and contralateral kidneys. The GFR in the stenosed kidney was not significantly lower in the contralateral kidney. FF was significantly higher in RAS rats than in C rats in both the stenosed and the contralateral kidneys, but the increase was less pronounced than in PAC and PAC + Nx rats.

Animals↗

Regulation of Na+-K+-ATPase activity in kidney proximal tubules: involvement of GTP binding proteins.

This study evaluates the involvement of GTP-dependent regulatory proteins (G-proteins) in the regulation of Na+-K+-ATPase activity in proximal convoluted tubule (PCT) segments. Single PCT segments were dissected from rat kidney and permeabilized to allow nucleotides and medium free access to the interior of the cell. A GDP analogue that blocks GTP-dependent activation of the G-protein, GDP beta S (400 microM) significantly inhibited PCT Na+-K+-ATPase activity when Na in the medium (Nam) was greater than or equal to 70 mM. The inhibition was attenuated when Nam was 55 and 35 mM and was no longer significant when Nam was 25 mM. GDP beta S had no inhibitory effect on the activity of purified Na+-K+-ATPase. A nonhydrolyzable GTP analogue, GppNHp (50 microM) significantly increased Na+-K+-ATPase activity when Nam was 25 and 35 mM, but not when Nam was 55-140 mM. Dopamine (DA) and DA1 plus DA2 agonists significantly inhibit Na+-K+-ATPase activity. DA inhibition was competitively abolished by GppNHp. In PCT segments from rats pretreated with pertussis toxin, DA and DA1 plus DA2 agonist inhibition of Na+-K+-ATPase activity was abolished. In PCT segments from rats pretreated with cholera toxin, basal Na+-K+-ATPase activity was increased, but DA significantly inhibited Na+-K+-ATPase activity. Na+-K+-ATPase activity in PCT segments is regulated via a G-protein that stimulates Na+-K+-ATPase activity and a DA-activated pertussis toxin-sensitive G-protein that inhibits Na+-K+-ATPase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Na+-K+-ATPase is an effector protein for protein kinase C in renal proximal tubule cells.

Activators of protein kinase C (PKC) inhibit sodium transport in proximal tubules (PT) (M. Baum and S. R. Hays. Am. J. Physiol. 254 (Renal Fluid Electrolyte Physiol. 23): F9-F14, 1988. In this study we have evaluated the effect of PKC activators on the enzyme responsible for active sodium transport, Na+-K+-ATPase. Both endogenous (diacylglycerol, DAG) and exogenous (phorbol esters, PE) activators were used. Enzyme activity was determined in permeabilized single PT segments. In vehicle-incubated PT, Na+-K+-ATPase activity (pmol Pi.mm tubule-1.-1 h) was 1,403 +/- 128. The synthetic DAG, L-alpha-l-oleoyl-2-acetoyl-sn-3-glycerol (10(-4) M) significantly inhibited Na+-K+-ATPase activity to 673 +/- 51, P less than 0.05. The PE-phorbol 12,13-dibutyrate (PDBu), induced a time- and dose-dependent inhibition of Na+-K+-ATPase activity. Inhibition was significant at 15 and maximal at 20 min. Na+-K+-ATPase activity in PT incubated with PDBu was 796 +/- 171 (10(-8) M), 570 +/- 198 (10(-7) M), and 484 +/- 130 (10(-6) M). A PE that does not activate PKC, 4-alpha-phorbol didecanoate, did not inhibit Na+-K+-ATPase activity. PDBu 10(-7) M had no effect on purified Na+-K+-ATPase. Sphingosine (SP), a PKC inhibitor, abolished the inhibitory effect of PDBu (10(-7) M) on Na+-K+-ATPase activity. Dopamine (DA) is a physiological inhibitor of Na+-K+-ATPase activity in PT [A. Bertorello, T. Hökfelt, M. Goldstein, and A. Aperia Am. J. Physiol. 254(Renal Fluid Electrolyte Physiol. 23): F795-F801, 1988].(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Reduction of protein intake decreases glomerular filtration rate in young type 1 (insulin-dependent) diabetic patients mainly in hyperfiltering patients.

The influence of different protein intake on renal function was studied in 16 Type 1 (insulin-dependent) diabetic patients, aged 15-23 years, with onset of diabetes before puberty and with a duration of diabetes between 5 and 20 years. The glomerular filtration rate, renal plasma flow, albumin excretion rate, and blood pressure were examined in a cross-over randomised order after 10 days on isocaloric diets with either 10% (i.e. 0.9 +/- 0.06 g.kg-1.day-1) or 20% (1.9 +/- 0.1 g.kg-1.day-1) of the calories as protein, the latter being equal to the recommended diet. Dietary compliance was evaluated using fractional phosphate excretion and overnight urea excretion. Glomerular filtration rate was lower after the low-protein diet compared to the usual protein diet (p less than 0.001). Patients with glomerular filtration rate above +2 SD of the normal mean on the usual protein diet (n = 6) exhibited the steepest fall in glomerular filtration rate with a mean decrease of 20 ml/min compared to 7 ml/min in those with initially normal glomerular filtration (p = 0.01). Filtration fraction tended to decrease on low protein diet, more so in initially hyperfiltering patients (p = 0.09). Renal plasma flow remained unchanged. In patients with elevated glomerular filtration rate on usual protein diet, albumin excretion rate and systolic, but not diastolic blood pressure, were decreased on low protein diet (p = 0.03 and p = 0.01, respectively) but not in initially normal-filtering patients. Mean blood glucose and serum fructosamine were unchanged on both diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effect of low-dose dopamine infusion on urinary prostaglandin E2 excretion in sick, preterm infants.

In pharmacological doses dopamine (DA) will interact with several endocrine systems and both inhibit (prolactin, thyrotropin) and enhance (renin, angiotensin) hormonal release. In this study we have examined whether DA given to preterm neonates will influence prostaglandin (PG) production. The question is of importance since vasodilator PGs play a role in postnatal adaptation. We determined the effect of low dose DA infusion on the 24 h urinary PGE2 excretion rate (an index of renal PGE2 synthesis) in preterm infants. Six preterm neonates, with a 24-h requirement of 2 micrograms/kg per min DA treatment for oedema, moderate oliguria, poor peripheral perfusion and/or mild systemic hypotension were studied on days 2 (Day 1), 3 (Day 2, the day of DA infusion), and 4 (Day 3, DA discontinued) of life. Six preterm infants (control group) that did not require DA infusion were also studied to monitor possible spontaneous changes in the renal PGE2 production on days 2, 3 and 4 of life. In the control group urine output (Uv) and PGE2 excretion rate remained unchanged during the study. In the study group DA administration resulted in nearly two-fold increases in both the Uv (194%) and PGE2 excretion (182%). Urinary PGE2 excretion was, however, closely related to urine flow in both the control infants (Day 1-3) and the study group infants (Day 1-2). Since increased diuresis stimulates renal PGE2 production, our data suggest that the increased PGE2 excretion on Day 2 in the study group was not due to a direct effect of DA on PGE2 synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Dinoprostone↗

Kidney function in adults born with unilateral renal agenesis or nephrectomized in childhood.

We have evaluated the long-term prognosis in an unselected group of adult patients either uni-nephrectomized in childhood because of hydronephrosis or born with unilateral renal agenesis. Thirty-six patients aged 7-47 years were followed for 7-40 years. In 23 control subjects aged 20-47 years the glomerular filtration rate (GFR) and the p-aminohippuric acid clearance (CPAH) did not change significantly with age. In patients with a single kidney the size of that kidney was larger and GFR and CPAH were higher than single kidney values in control subjects. However, in patients with a single kidney since childhood the GFR and the CPAH declined slowly but significantly during the follow-up period. Significant microalbuminuria occurred in 47% of the patients with a single kidney and was more frequent with a longer follow-up period. No patient had renal insufficiency or a marked increase in arterial blood pressure. We conclude that in patients with a single kidney since childhood the long-term prognosis is good, but the late decrease in GFR and increase in albumin excretion may indicate a moderate risk for premature renal damage.

Adaptation, Physiological↗

Mitotic response to high protein intake in different renal cell types in weanling rats.

We examined the effect of high protein intake on the mitotic response (3H-thymidine incorporation) in the glomerulus, proximal tubule (PT), thick ascending limb of Henle (TAL), distal tubule (DT) and collecting duct (CD) in kidneys from 16- to 24-day-old rats that received an isocaloric diet containing 21% (NP) and 50% (HP) protein from 16 days of age. Nephron filtration rate was also determined. After two days of HP diet, thymidine incorporation (TI) was significantly increased in PT and TAL. After two days on HP diet TI was most pronounced in TAL. After eight days on HP diet TI remained elevated in PT, but not in TAL. HP did not increase TI in DT or CD. The glomerular TI was the same in HP as in NP rats after two and four days on the diet, but was significantly elevated after eight days on HP diet. The nephron filtration rate was increased after two days and remained significantly elevated after eight days on HP diet. The proximal tubule fractional reabsorption was the same in 24-day-old NP and HP rats. We conclude that the results are compatible with the hypothesis that the Na load is a major factor triggering tubular growth after HP intake. Glomerular growth is secondary to increase in nephron filtration rate.

Animals↗

Postnatal development of renal function in very low birthweight infants.

The postnatal development of renal function was compared in infants with a gestational age of 25-30 weeks, mean 27.8 weeks (GA 28), and in infants with a gestational age of 31-34 weeks, mean 32.5 weeks (GA 32). The infants were comparable with regard to postnatal course, fluid, caloric and salt intake. Observations were made during the 1st, 2nd and 4th-7th (mean 5th) postnatal weeks. From the 1st to the 5th postnatal week the creatinine clearance (CCr ml/min/1.73 m2), increased from 11 to 20 in GA 28 and from 15 to 30 in GA 32. At 2 weeks of age CCr was significantly lower in GA 28 than in GA 32. During the first week of life diuresis was lower in GA 28 than in GA 32 but thereafter was the same in both groups. We interpret this as a sign of dehydration in GA 28. Serum arginine vasopressin (S-AVP) concentrations were high in both groups at all ages. Mean urine osmolality was low (less than 300) regardless of postnatal age and S-AVP. Urinary sodium excretion was high at 1 week of age in both groups and decreased with increasing postnatal age. Na excretion was slightly higher in GA 28 than in GA 32 at 1 but not at 2 and 5 weeks. UK/UNa was below 1 in both groups during the first week of life and increased with postnatal age. Urinary aldosterone excretion was high in both GA 28 and GA 32 at all ages. Serum sodium levels were lower in GA 28 than in GA 32 at all ages.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗

Hypocalcemia and hyperphosphatemia in severely dehydrated children with and without convulsions.

Tetanic convulsions are not uncommon among severely dehydrated children in the developing countries. This raises the question whether these children have disturbances in the homeostasis of divalent ions. Serum values are reported of calcium, magnesium, phosphorus, sodium and potassium, as well as blood pH in children below 3 years of age with acute watery diarrhoea and with an estimated weight loss of about 10%. The study was performed on dehydrated children with (DC) or without (D) convulsions. Values were obtained on admission and following rehydration therapy (RT). On admission serum calcium was low in both D and DC children. Serum phosphorus was likewise elevated in both D and DC children. Serum magnesium was slightly elevated in the DC but not in the D group. No patient had hypernatremia. During RT, serum calcium increased significantly and serum phosphorus decreased significantly in D and DC children. Serum calcium showed a significant inverse correlation with serum phosphorus and a significant direct correlation with blood pH. Treatment of DC children with i.v. calcium and i.m. magnesium had no immediate effect on the convulsions. Our conclusion is that severely dehydrated children will develop hypocalcemia. The cause may be a redistribution of calcium into the cells, parallelled by a redistribution of phosphorus from the intra- to the extracellular space.

Child, Preschool↗

Studies on terminal differentiation of rat renal proximal tubular cells in culture: ouabain-sensitive K and Na transport.

We have studied the ontogeny of Na-K ATPase-mediated Na and K transport in rat renal proximal tubular cells using electron probe analysis. The cells were cultured from kidneys of 10-day-old, young (Y), and 40-day-old, adult (A) rats. Before an experiment cells were Na-loaded and K-depleted by incubation in K-free medium. The maximum rate of ouabain-sensitive Na and K transport was measured after reactivating the Na-K pump by transferring the cells from K-free medium to medium containing 5 mM K. In cells cultured for 2 days, ouabain-sensitive Na and K net initial transport rates were significantly higher in A than in Y cells. Between 2 and 4 days in culture there was a significant decrease in ouabain-sensitive Na and K transport rates in both Y and A cells. From 2 to 4 days of culture there was, in Y but not in A cells, a significant decrease in K/Na ratio. The decrease in K/Na ratio was due to a significant increase in Na content. After incubation in K-free medium, net intracellular solute accumulation was observed in A and Y cells cultured for 4 days but not in A and Y cells cultured for 2 days. In conclusion, maximal Na- and K-pump-mediated transport increases during terminal differentiation. This increase can be measured in cells cultured for 2 days. With longer time in culture, Na-K pump activity decreases and the difference between A and Y cells is not measurable.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Contribution of dopamine 2 receptors to dopamine-induced increase in glomerular filtration rate.

The effects of the interaction of dopamine (DA) and the DA2 receptors on glomerular filtration rate (GFR) has been studied by means of micropuncture technique in adult greater than or equal to 60-day-old and young 24-day-old rats. Most of the studies were performed in rats with intact adrenergic nervous systems to allow for evaluation of the presynaptic DA2 receptors. In adult and young rats, DA and LY-171555 (LY), a selective DA2 receptor agonist, induced prompt and significant increases in the single nephron (SN) GFR. Further studies were performed only in adult rats. The LY-induced increase in SNGFR was completely abolished during DA2 receptor blockade with S-sulpiride (S-SP), while the DA-induced increase in SNGFR was attenuated but still significant during S-SP treatment. Both DA and LY significantly increased the glomerular ultra-filtration pressure (PUFAA). In rats with ganglionic blockade, the LY-induced increase of SNGFR was attenuated but still significant, whereas the DA-induced increase was less affected. The results imply that DA significantly increases GFR by interacting with the DA2 as well as with the DA1 receptors. Interaction between DA and the DA2 receptors increases PUFAA. The results do not rule out the existence of both pre- and postsynaptic renal DA2 receptors.

Animals↗

Proximal tubule Na+-K+-ATPase activity is inhibited during high-salt diet: evidence for DA-mediated effect.

Locally produced dopamine (DA) causes a reversible and dose-dependent inhibition in Na+-K+-ATPase activity in rat proximal tubule (PT) segments [A. Aperia, A. Bertorello, and I. Seri. Am. J. Physiol. 252 (Renal Fluid Electrolyte Physiol. 21): F32-F45, 1987.]. To examine whether this effect might be of physiological importance, rats were given normal-salt (NS) or high-salt (HS) diet for 10 days. HS diet significantly increased Na excretion but did not alter glomerular filtration rate (GFR). Benserazide (Bz), an inhibitor of the enzyme L-aromatic amino acid decarboxylase (AADC) that converts L-dopa to DA, significantly attenuated the natriuresis in HS rats but had no effect on GFR. By use of immunofluorescence (IF) studies AADC was localized to the PT. Specific AADC IF was not observed in the medulla. In AADC-positive PT segments, Na+-K+-ATPase activity was significantly lower in HS rats than in NS rats (P less than 0.001). In AADC-negative medullary thick ascending limb, Na+-K+-ATPase activity was the same in NS and HS rats. If HS rats were given Bz just before study, PT Na+-K+-ATPase activity increased significantly and was not different from Na+-K+-ATPase activity in PT segments from NS rats. Bz had no significant effect on PT Na+-K+-ATPase activity in NS rats. In PT segments from Bz-treated rats, DA inhibited Na+-K+-ATPase activity already at a dose of 10(-8) M, whereas in segments from NS rats, significant inhibition of Na+-K+-ATPase activity was not observed until DA was increased to 10(-7) M.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Differentiation of Na+-K+ pump in rat proximal tubule is modulated by Na+-H+ exchanger.

This study examines the effect of in vivo modulation of Na+-H+ exchange activity on the development of Na+-K+-ATPase in rat kidney proximal convoluted tubule (PCT) segments. To stimulate Na+-H+ exchanger (major entry pathway for Na in PCT), weanling rats were fed NH4Cl for 4 days to induce metabolic acidosis (MA). In vehicle (Vh)-fed rats PCT Na+-K+-ATPase activity (pmol Pi.mm tubule-1.h-1 +/- SE) increased from 481 +/- 78 at 16 days to 1,122 +/- 119 at 20 days. In 20-day-old chronic MA rats, PCT Na+-K+-ATPase activity was 1,717 +/- 109, i.e., significantly higher (P less than 0.01) relative to controls. Chronic MA had no effect on PCT Mg ATPase activity and on Na+-K+-ATPase in the medullary thick ascending limb (MTAL). To inhibit the Na+-H+ exchanger, weanling rats received amiloride (30 micrograms.100 g body wt-1.day-1) via osmotic minipump for 4 days. In Vh-treated rats PCT Na+-K+-ATPase increased from 481 +/- 78 at 16 days to 1,428 +/- 81 at 20 days. In rats given chronic amiloride, PCT Na+-K+-ATPase was significantly lower (858 +/- 75) at 20 days relative to controls but PCT Mg ATPase and MTAL Na+-K+-ATPase activity was the same as in controls. Chronic MA and amiloride had no significant effect on PCT Na+-K+-ATPase activity in adult rats. Acute MA and acute amiloride injection had no significant effect on PCT Na+-K+-ATPase in weanling rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗

Locally formed dopamine inhibits Na+-K+-ATPase activity in rat renal cortical tubule cells.

Dopamine, generated locally from L-dopa, inhibits Na+-K+-ATPase in permeabilized rat proximal tubules under maximum transport rate conditions for sodium. To determine whether locally formed dopamine inhibits Na+-K+-ATPase activity in intact cortical tubule cells we studied the effect of L-dopa on ouabain-sensitive oxygen consumption rate (QO2) and 86Rb uptake in renal cortical tubule cell suspensions. L-Dopa (10(-4) M) did not affect ouabain-insensitive QO2 or mitochondrial respiration. However, L-dopa inhibited ouabain-sensitive QO2 in a concentration-dependent manner, with half-maximal inhibition (K0.5) of 5 x 10(-7) M and a maximal inhibition of 14.1 +/- 1.5% at 10(-4) M (P less than 0.05). L-Dopa also blunted the nystatin-stimulated QO2 in a concentration-dependent manner, with a K0.5 of 5 x 10(-8) M and a maximal inhibition of 21.8 +/- 1.2% at 10(-5) M (P less than 0.05), indicating that L-dopa directly inhibits Na+-K+-ATPase activity and not sodium entry. Ouabain-sensitive 86Rb uptake was also inhibited by L-dopa (16.0 +/- 2.4%, P less than 0.05). Carbidopa (10(-4) M), an inhibitor of the conversion of L-dopa to dopamine, eliminated the effect of L-dopa on ouabain-sensitive QO2 and 86Rb uptake, indicating that dopamine rather than L-dopa was the active agent. The finding that the L-dopa concentration-response curve was shifted to the left by one order of magnitude in the presence of nystatin suggests that the inhibitory effect is enhanced when the intracellular sodium concentration is increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Use of experimental models to study the development of renal function.

By use of animal experiments it has been demonstrated that renal cells are immature at birth. Membrane transport is quantitatively and qualitatively different. The control of fluid and electrolyte balance is therefore different in infancy. The increased filtered load at birth as well as hormones will induce tubule maturation. The use of animal experiments will in the future give an insight into how external factors influence growth and maturation.

Animals↗