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Biomedical subjects

J Gaya

Publications and source records attributed to J Gaya.

At least 55 records · Page 3Linked to original sources

Arginine-vasopressin in essential hypernatremia.

Dynamics of AVP secretion in a 14-year-old girl with essential hypernatremia, psychomotor retardation and optic nerve coloboma, are reported. Basal levels of AVP were similar to those of a control population, but disproportionately low in relation with natremies. Hypertonic saline and hydric restriction did not alter the AVP basal values, which were, instead, stimulated with orthostatism. AVP decreased during a water surcharge, but delayed elimination of water was observed. The existence of a moderate volume deficit, not corrigible with a chronic surcharge of water, together with the reversed diurnal pattern of water excretion and the AVP data, suggest--as a physiopathological basis of the syndrome--a severe anomaly of the osmoreceptors, with alteration of thirst and of the osmodependent AVP responses, so that the AVP secretion was regulated exclusively through volumetric mechanisms.

Adolescent↗

Urinary excretion of 6-keto-prostaglandin F1 alpha, thromboxane B2 and prostaglandin E2 in cirrhosis with ascites. Relationship to functional renal failure (hepatorenal syndrome).

The aim of the study was to investigate the urinary excretion of 6-keto-PGF1 alpha (a stable metabolite of PGI2), thromboxane B2 (TxB2; a stable metabolite of TxA2), and PGE2 in 18 normal subjects, 49 cirrhotics with ascites without renal failure (GFR = 90 +/- 4 ml/min, means +/- S.E.M.) and 20 cirrhotics with functional renal failure (FRF) (GFR = 36 +/- 3). The study was made after 5 days on a 50 mEq sodium diet and without diuretics. Plasma renin activity (PRA), plasma norepinephrine concentration (NE) and plasma antidiuretic hormone concentration (ADH) were also measured. Cirrhotics without FRF showed a significantly higher urinary excretion of 6-keto-PGF1 alpha, TxB2 and PGE, (15.9 +/- 1.7 ng/h, 3.0 +/- 0.3 ng/h, and 6.2 +/- 1.0 ng/h) than did normal subjects (9.2 +/- 0.9, 1.3 +/- 0.1 and 2.3 +/- 0.4). On the contrary, the urinary excretion of these prostaglandins was normal or reduced in patients with FRF (5.3 +/- 0.8, 1.3 +/- 0.2 and 1.9 +/- 0.4). PRA, NE and ADH were significantly increased in cirrhotics with FRF (15.2 +/- 3.9 ng/ml/h, 1026 +/- 149 pg/ml and 4.1 +/- 0.3 pg/ml) and in patients without FRF (8.0 +/- 1.4, 667 +/- 67 and 3.9 +/- 0.3) as compared to normal controls (1.3 +/- 0.2, 275 +/- 46 and 2.4 +/- 0.2). These results suggest that renal hemodynamics in cirrhosis depends upon a critical equilibrium between the activity of endogenous vasoconstrictor systems and the renal production of the vasodilator prostaglandins PGI2 and PGE2. In addition, they do not support FRF in cirrhosis being related to an increased renal production of the vasoconstrictor prostaglandin TxA2.

6-Ketoprostaglandin F1 alpha↗

Atrial natriuretic factor: reduced cardiac content in cirrhotic rats with ascites.

The present study was designed to investigate whether cirrhosis with ascites is associated with altered tissue content of atrial natriuretic factor. Atrial extracts from 14 cirrhotic rats with ascites and increased plasma renin activity (PRA) (14.4 +/- 4.6 ng X ml-1 X h-1) and aldosterone concentration (148.3 +/- 17.3 ng/dl) and from 10 control rats (PRA, 3 +/- 0.5 ng X ml-1 X h-1; aldosterone, 34.7 +/- 3.7 ng/dl) were intravenously injected into anesthetized normovolemic rats. Only one extract was assayed in each bioassay rat. Atrial extracts from control rats increased diuresis and natriuresis 513 +/- 91 and 3,029 +/- 752%, respectively (means +/- SE). In contrast, atrial extracts from cirrhotic rats increased urine volume 199 +/- 49% (P less than 0.001) and sodium excretion 546 +/- 132% (P less than 0.001). These results strongly suggest that atrial content of atrial natriuretic factor is reduced in cirrhotic rats as compared with control animals.

Animals↗

Sulindac reduces the urinary excretion of prostaglandins and impairs renal function in cirrhosis with ascites.

In 5 patients with cirrhosis and ascites the glomerular filtration rate (GFR), free water clearance (CH2O) and urinary excretion of prostaglandin E2(PGE2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were measured before and after a 3-day treatment with sulindac (400 mg/day). The administration of sulindac induced a marked fall of urinary excretion of PGE2 (from 24.2 +/- 5.5 to 3.8 +/- 1.1 ng/h; p less than 0.05), 6-keto-PGF1 alpha (from 19.9 +/- 2.9 to 5.6 +/- 1.1 ng/h; p less than 0.02) GFR (from 111 +/- 15 to 67 +/- 10 ml/min; p less than 0.01) and CH2O (from 7 +/- 1.5 to 3.7 +/- 1.3 ml/min; p less than 0.02) in all patients studied. The plasma concentration of the active metabolite sulindac sulfide in cirrhotics was 400% of that found in 6 healthy volunteers (9.6 +/- 1.7 vs. 2.4 +/- 0.6 ng/ml). Our results indicate that sulindac, at a dose of 400 mg/day, inhibits the renal synthesis of prostaglandins and impairs renal function in cirrhotics with ascites. These effects are probably related to the marked alteration of sulindac kinetics that occurs in these patients.

6-Ketoprostaglandin F1 alpha↗

Neurohormonal responses to antihypertensive treatment with captopril or hydrochlorothiazide.

In order to assess the neurohormonal responses to oral administration of two drugs with different antihypertensive mechanisms, and their implications for long-term efficacy, we studied the changes in plasma renin activity, aldosterone, catecholamines and blood pressure after two cross-over periods of treatment with captopril and hydrochlorothiazide for three months in 14 patients with moderate essential hypertension. Similar levels of plasma renin activity were achieved with both but plasma levels of noradrenaline and aldosterone rose with hydrochlorothiazide (P less than 0.005 and P less than 0.05). Dopamine levels decreased with captopril. Six patients on hydrochlorothiazide had potassium levels under 3.5 mmol/l. Captopril and hydrochlorothiazide were effective in controlling blood pressure in 78% and 50% of the patients respectively, but in cases where noradrenaline was significantly increased after treatment, the effect on diastolic blood pressure was less (P less than 0.05). These data suggest that captopril is highly effective for blood pressure control and that the neurohormonal responses to the drug probably provide additional benefits for long-term therapy in hypertension.

Adult↗

[Technics for the study of the renal excretion of free water in normal rats and those with experimental liver cirrhosis].

Different techniques to measure free water excretion in rats, administered an oral water overload and with measurement of its ability to excrete it into the urine have been studied. When 30 or 50 ml/kg b.wt. were administered and the urine excreted in 3 h was collected, a decrease on the urinary osmolality (UOSM) was observed with respect to the baseline UOSM, which was similar in both overloads, although the percentage of the overload excreted was significantly greater with 50 ml/kg. However, the UOSM obtained was hypertonic as compared to plasma osmolality (POSM) indicating that this determination was not useful to study free water excretion. In a further study it was investigated if there was any period of time in which all the animals excreted hypotonic urine. However, results indicated that the period for excreting a maximally diluted urine was very variable in time. The best technique to study free water excretion in these animals was the collection of each spontaneously voided urine independently, to measure the minimal UOSM. When a 50 ml/kg water load was administered and the minimal UOSM was determined it was observed to be lower than POSM in all the animals indicating that this technique was useful to study this derangement in these animals.

Animals↗

[Determination of arginine-vasopressin in small volumes of rat plasma].

A radioimmunoassay to determine arginine-vasopressin concentration in rat plasma is described. This method was a modification from a previously described technique from which the incubation volume was reduced. It allows us to use only 300 microliter of plasma, 1/4 of the original volume, without any impairment to the sensitivity. The intra- and inter-assay coefficients of variation are 11% and 13% respectively. The accuracy ranges between 90 and 99%. To investigate the influence of sampling blood conditions on arginine-vasopressin levels, five groups of Sprague-Dawley rats are analyzed: Group I, decapitation; Group II, ether anaesthesia and cardiac puncture; Group III, ether anaesthesia and decapitation; Group IV, ketamine anaesthesia and cardiac puncture; Group V, ketamine anaesthesia and decapitation. Arginine-vasopressin levels in Group V (2.2 +/- 0.8 pg/ml) are significantly lower than those from the other four groups and similar to those obtained by other authors using a chronic catheter.

Animals↗

Renal hemodynamic abnormalities in patients with short term insulin-dependent diabetes mellitus: role of renal prostaglandins.

To determine if renal functional alterations in diabetes mellitus could be related to disturbances of vasoactive systems, renal plasma flow (RPF), glomerular filtration rate (GFR), PRA (basal and stimulated), plasma catecholamine levels, and urinary excretion of prostaglandin E2 (PGE2), 6-keto-PGF1 alpha, and kallikrein were determined in 21 patients with insulin-dependent diabetes mellitus (IDDM) of short duration and 15 normal subjects. In 7 additional patients with IDDM and in 4 normal subjects, the effect of lysine acetylsalicylate (LAS; 450 mg, iv) on GFR and RPF was studied. Patients with IDDM had higher RPF and GFR than normal subjects. Plasma norepinephrine and basal and stimulated PRA were significantly lower in IDDM than in the control group [161 +/- 82 (+/- SD) vs. 243 +/- 114 pg/ml, 0.19 +/- 0.20 vs. 1.15 +/- 0.33 ng/ml X h, and 0.93 +/- 0.82 vs. 2.8 +/- 1.73 ng/ml X h, respectively). No significant differences were found in the urinary excretion of PGE2, 6-keto-PGF1 alpha, and kallikrein in the two groups. LAS administration significantly reduced RPF (from 641 +/- 72 to 535 +/- 38 ml/min X 1.73 m2) and GFR (from 168 +/- 25 to 150 +/- 18 ml/min X 1.73 m2) in patients with IDDM, but not in normal subjects. In IDDM patients, there was a close direct correlation between the percent decrease in RPF and GFR induced by LAS and the baseline values of these parameters. The results suggest that in IDDM, there may be an imbalance between the degree of activation of the renin-angiotensin and sympathetic nervous systems and the renal production of PGs. The observation that LAS administration reduced RPF and GFR in these patients suggests that renal PGs are involved in the renal hyperperfusion of IDDM.

Adult↗

[Effect of the method of blood extraction on plasma levels of renin in the Wistar rat].

To investigate the influence of blood extraction conditions on the renin-angiotensin system in rats, plasma renin activity (PRA) and plasma renin concentration (PRC) were measured in blood samples obtained by different methods. PRA and PRC in samples obtained by chronic catheterization, cardiac puncture without anesthesia, and decapitation immediately following light ether anesthesia were not significantly different from those obtained by simple decapitation (control group). In contrast, PRA and PRC in samples obtained by cardiac puncture and cavernous sinus puncture after light ether anesthesia were significantly (p less than 0.01) higher than those obtained in the control group. There was a significant direct correlationship between PRA and PRC in all samples studied (r = 0.87, p less than 0.001). The present results suggest that light ether anesthesia increases renin levels, except when blood samples are taken by decapitation, and that chronic catheterization and cardiac puncture are the choice blood extraction methods to evaluate the renin-angiotensin system in rats.

Anesthesia, General↗

Evidence that renal prostaglandins are involved in renal water metabolism in cirrhosis.

Plasma antidiuretic hormone (ADH) and urinary prostaglandin E2 excretion (UPGE2V) were measured in basal conditions, after water restriction, and after water-loading in 10 normal subjects (free water clearance after the water load, CH2O, 9.6 +/- 0.8 ml/min) and in 27 patients with cirrhosis and ascites (13 with a positive CH2O: 3.6 +/- 0.5; 14 with a negative CH2O: -0.37 +/- 0.007). Plasma ADH and UPGE2V were significantly increased in patients with a positive CH2O as compared with normal subjects. Patients with a negative CH2O showed a significantly higher plasma ADH and a lower UPGE2V and GFR than did normal subjects and patients with the positive CH2O. In 18 additional subjects (6 normal and 12 with cirrhosis, ascites, and a positive CH2O) submitted to a sustained water overload, the i.v. administration of 450 mg of lysine acetylsalicylate (LAS) induced a marked reduction of UPGE2V, but it had no effect on plasma ADH. LAS did not alter GFR and CH2O in normal subjects; however, it reduced CH2O in all the 12 patients (from 5.1 +/- 0.4 to 0.6 +/- 0.3) and the GFR in only 6 of these patients. These results suggest (a) that renal PGE2 plays an important role in the maintenance of water excretion in cirrhosis with ascites, and (b) that impaired ability to dilute the urine in cirrhosis may be a consequence of the simultaneous occurrence of impaired renal hemodynamics, nonostomic hypersecretion of ADH, and reduced renal production of PGE2.

Arginine Vasopressin↗

Studies on the mechanisms of somatostatin release after insulin induced hypoglycaemia in man.

Insulin-induced hypoglycaemia, which stimulates gastric acid secretion, is associated with an increase in circulating somatostatin levels in man. In order to assess the mechanisms involved in this rise, six normal volunteers connected to a Biostator for continuous glucose monitoring were studied, on three separate occasions. On each occasion after basal blood sampling, 0.15 i.u./kg body weight of insulin was administered i.v. and further samples were obtained intermittently over 150 min. On one occasion, dextrose was infused by the Biostator to prevent hypoglycaemia, while on the other two, a constant infusion of either normal saline or the specific H2 antagonist cimetidine was administered. Insulin plus dextrose caused no significant changes in circulating somatostatin levels, whereas insulin plus saline was associated with a marked, sustained and significant rise in all subjects; insulin plus cimetidine also produced a rise but it was delayed; the area under the curve was significantly (P less than 0.05) greater with insulin plus saline than with insulin plus cimetidine. These results show that in man insulin itself does not stimulate somatostatin secretion directly, but indirectly via hypoglycaemia. Further, the inhibition of gastric acid secretion with cimetidine reduces somatostatin release during insulin-induced hypoglycaemia. This suggests that gastric acid may mediate somatostatin secretion associated with insulin-induced hypoglycaemia.

Adult↗

Effect of demeclocycline on renal function and urinary prostaglandin E2 and kallikrein in hyponatremic cirrhotics.

8 cirrhotics with hyponatremia were given demeclocycline (DMC) 900 mg/day to investigate its effect on renal function, plasma renin activity, aldosterone and urinary excretion of prostaglandin E2 and kallikrein. In 7 patients DMC induced an increase of free water clearance (from -0.36 +/- 0.06 to 0.13 +/- 0.06 ml/min) and serum sodium concentration (from 125.4 +/- 0.09 to 131.1 +/- 1.0 mEq/l, mmol/l). In 5 of these patients DMC also induced a marked reduction of glomerular filtration rate (from 72.2 +/- 6.2 to 31,2 +/- 4.7 ml/min) and renal plasma flow (from 468 +/- 98 to 195 +/- 55 ml/min) which could not be explained on the basis of hypovolemia. In each case this renal impairment was not associated with changes in urinary concentration of beta 2-microglobulin, urinary casts excretion, fresh urine sediment or urine protein content and disappeared after discontinuation of the drug. DMC induced a marked increase in the urinary excretion of prostaglandin E2 (from 0.82 +/- 0.27 to 6.16 +/- 1.91 ng/min) in 6 out of the 7 patients who responded to DMC and a marked reduction in urinary kallikrein (from 16.1 +/- 4.4 to 4.2 +/- 1.6 pkat/min) in the 5 patients who developed renal insufficiency. The serum DMC concentration was greater than 5 micrograms/ml in all patients who responded to DMC, greater than 8 micrograms/ml in all cases who developed renal insufficiency and of 3 micrograms/ml in the case not responding to DMC. (ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

Use of the urologic resectoscope in rectal pathology.

We have resected five sessile polyps and treated rectal hemorrhage using the urologic resectoscope that operates in an aqueous solution. It is our belief that working in an aqueous environment can avoid some of the drawbacks of the standard technique in an air environment. We think that this is a useful technique in digestive endoscopy with precise indications and promising future development.

Colonoscopes↗

Beta adrenergic modulation of extrarenal potassium disposal in terminal uraemia.

In order to study the effect of epinephrine on potassium (K) metabolism, an epinephrine infusion (0.1 micrograms/kg/min for 30 min) was carried out in 12 essentially anuric and usually hyperkalaemic haemodialysis patients, 72 hr post-dialysis. Two groups emerged, group I (five patients) serum K decreased at least 0.75 mEq/L (from 6.6 +/- 0.2 to 5.4 +/- 0.1 mEq/L) and there were increases in heart rate, serum glucose and insulin values, group II (seven patients), serum K did not decrease and heart rate remained unchanged, but serum glucose and insulin increased slightly. Plasma renin, aldosterone and arterial pH did not change in either group. Propranolol blocked the epinephrine induced decrease in serum K in group I patients. Patients from group II had higher pre-infusion endogenous epinephrine concentrations than patients from group I. In haemodialysis patients beta adrenergic stimulation enhances extrarenal K disposal but about 50 per cent of patients fail to respond, perhaps because of receptor occupancy due to higher endogenous epinephrine concentrations.

Adrenergic beta-Agonists↗

[Specificity of the determination of urinary kallikrein activity using an amidolytic assay].

The specificity of a method for the determination of the urinary kallikrein activity based on the amidolytic hydrolysis of the synthetic substrate H-D-valyl-leucyl-arginine-p-nitroanilide has been studied. Results show a good specificity for kallikrein. The amidolytic activity was totally inhibited by aprotinin. The urinary amidolytic activity showed identical dependence on changes in the ionic strength and pH of the incubation medium as the highly purified kallikrein. The sensitivity of the assay was 0.6 nkat/l. The intra-assay coefficient of variation was 4% and the inter-assay coefficient of variation was 10%. The percentage of recovery was between 100 and 110% indicating that no activators or inhibitors of the kallikrein activity on this substrate were present in the urinary samples. Values obtained in presumably healthy subjects were 0.14 +/- 0.08 pkat/s in man (range: 0.05 - 0.27 pkat/s) and 0.49 +/- 0.11 pkat/s in rat (range: 0.35 - 0.58 pkat/s).

Adult↗

Randomized comparative study of efficacy of furosemide versus spironolactone in nonazotemic cirrhosis with ascites. Relationship between the diuretic response and the activity of the renin-aldosterone system.

Loop and distal diuretics are the basic drugs for the treatment of ascites. Although pharmacologic studies indicate that the natriuretic potency of loop diuretics is much greater than that of distal diuretics, there are no studies comparing the efficacy of these drugs in cirrhosis. Forty nonazotemic cirrhotic patients with ascites and avid sodium retention were randomly allocated into two groups. Group 1 contained 21 patients treated with furosemide; group 2 contained 19 patients treated with spironolactone. The initial doses were 80 and 150 mg/day, respectively. These doses were increased to 160 and 300 mg/day, respectively, if there was no response. Cases not responding to furosemide and spironolactone were later treated with spironolactone and furosemide, respectively. In group 1, 11 of the 21 patients responded to furosemide, while in group 2, 18 of the 19 patients responded to spironolactone (p less than 0.01). Of the 10 patients in group 1 not responding to furosemide, 9 responded later to spironolactone. The diuretic response to furosemide and spironolactone was related to the activity of the renin-aldosterone system. Patients with higher renin and aldosterone did not respond to furosemide and required 300 mg/day of spironolactone to achieve a diuretic response. These results indicate that (a) at the dosages used in the study, spironolactone is more effective than furosemide in nonazotemic cirrhosis with ascites, and (b) the activity of the renin-aldosterone system influences the diuretic response to furosemide and spironolactone in these patients.

Ascites↗