Desmopressin tablet treatment in nocturnal enuresis.
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Administration, Oral↗
Biomedical subjects
A Stenberg
Publications and source records attributed to A Stenberg.
Renal tubular apoptosis after partial ureteral obstruction.
Partial ureteral obstruction in the weanling rat leads to hydronephrosis of the ipsilateral kidney and renal cell deletion through the process of programmed cell death known as apoptosis. The apoptotic response following partial ureteral obstruction in weanling Sprague-Dawley rats was studied using the traditional markers of apoptosis, including deoxyribonucleic acid (DNA) laddering pattern on agarose gel electrophoresis, in situ gap labeling of fragmented DNA for quantitative apoptotic body determination, polyadenylated messenger ribonucleic acid (mRNA) expression of sulfated glycoprotein-2, and polyadenylated mRNA expression of epidermal growth factor and transforming growth factor-beta. Partial ureteral obstruction resulted in a progressive increase in the intensity of DNA fragmentation associated with apoptosis during the initial 3 weeks. Quantitative apoptotic body counting revealed a 3-fold increase by week 3 of partial obstruction. This increase represented a level of apoptosis, which is 65% of that observed in complete ureteral obstruction. By week 2 of partial obstruction there was a 13-fold increase in the expression of sulfated glycoprotein-2 mRNA, as well as changes in the growth factor environment characterized by a decline in the constitutive expression of epidermal growth factor mRNA and an increase in the expression of transforming growth factor-beta mRNA. These altered levels represent changes in expression comparable to those observed during the apoptotic response following complete ureteral obstruction, although the time course is delayed by 2 to 3 weeks.
Animals↗
Desmopressin tablets in the treatment of severe nocturnal enuresis in adolescents.
BACKGROUND: In recent years the treatment of primary nocturnal enuresis (PNE) with desmopressin (DDAVP) has been promising. The route of administration until now had been intranasal, but because the tablets were introduced for the treatment of diabetes insipidus they have also become available for the treatment of PNE. OBJECTIVES: To find the optimal dosage of desmopressin tablets and to compare desmopressin's efficacy with placebo in a group of adolescents with severe monosymptomatic enuresis. The long-term safety of desmopressin was also studied in the same group of patients. METHODS: The effect of oral desmopressin (1-deamino-8-D-arginine-vasopressin) (DDAVP tablets, Minirin) was investigated in 25 adolescents (ages 11 to 21 years) with severe monosymptomatic nocturnal enuresis. The first part of the dose-ranging study comprised a single-blind dose titration period, followed by a double-blind, crossover efficacy period comparing desmopressin with placebo. The final part was an open long-term study consisting of two 12-week treatment periods. The efficacy of the drug was measured in reductions of the number of wet nights per week. RESULTS: During the first dose-titration period, the majority of the patients were given desmopressin 400 micrograms, and the number of wet nights decreased from a mean of 4.9 to 2.8. During the double-blind period, a significant reduction of wet nights was observed (1.8 vs 4.1 for placebo). During the two long-term periods, 48% and 53% of the patients could be classified as responders (0 to 1 wet night per week) and 22% and 23.5% as intermediate responders (2 to 3 wet nights per week). No weight gain was observed due to water retention. After cessation of the drug, 44% of the patients had a significant decrease in the number of wet nights. CONCLUSIONS: Oral desmopressin has a clinically significant effect on patients with PNE, and therapy is safe when administered as long-term treatment.
Adolescent↗
Treatment with oral desmopressin in adolescents with primary nocturnal enuresis. Efficacy and long-term effect.
Twenty-four adolescents, mean age 13.5 years, with primary nocturnal enuresis (PNE), were studied to evaluate the efficacy of long-term oral desmopressin use. Reduction in mean number of wet nights per week was the criterion for response. Results showed that during 12-week treatment Period I, 48% were full responders (< or = 1 wet night/wk); 22% were intermediate responders (2 to 3 wet nights/wk); and 30% were nonresponders (> 3 wet nights/wk). During 12-week treatment Period II, 53% were full responders, 23.5% were intermediate responders, and 23.5% were nonresponders. Despite a high relapse rate (50% after Period I, 56% after Period II), 17 patients (71%) were completely dry 2 years posttreatment, suggesting a possible curative effect of oral desmopressin. It was concluded that oral desmopressin is comparable to the intranasal formulation, with a good, long-term therapeutic effect in adolescents with PNE.
Administration, Oral↗
Renal interstitial pressure and tubuloglomerular feedback control in rats during infusion of atrial natriuretic peptide (ANP).
Atrial natriuretic peptide (ANP), injected at physiological concentrations, is known to induce both natriuresis and diuresis. It has been suggested by some investigators that these changes result from an increasing glomerular filtration rate (GFR), but others have been unable to demonstrate an increased GFR. The tubuloglomerular feedback (TGF) mechanism is an important regulator of GFR, and the sensitivity of TGF is decreased during ANP administration. Furthermore, resetting of TGF is, in most instances, related to changes in renal interstitial hydrostatic and oncotic pressures. It is also known that ANP may increase capillary permeability which may change renal interstitial pressure. The present study was performed to examine renal interstitial pressures and the TGF mechanism during ANP infusion. In accordance with previous studies, TGF sensitivity was found to be decreased. The tubular flow rate which elicited half the maximal drop in stop-flow pressure (Psf) was increased from 18.5 to 25.7 nl min-1. In contrast, ANP infusion resulted in a decreased interstitial hydrostatic pressure and an increased interstitial oncotic pressure. From previous experiments, such changes in interstitial pressures would be expected to increase TGF sensitivity. The changes in interstitial pressure cannot, therefore, directly explain the resetting of the feedback mechanism. In conclusion, the present paper shows a decreased renal net interstitial pressure after intravenous administration of ANP.
Animals↗
Long-term partial ureteral obstruction and its effects on kidney function.
Previously it has been shown that partial ureteral obstruction present in young rats for 12 weeks results in small morphological changes in the kidney as well as slightly decreased kidney function. In the present study the aim was to examine whether rats obstructed for one year had more advanced changes in morphology and kidney function. The first group of animals examined after three weeks of obstruction showed only modest changes in kidney function with a reduced potassium concentration in the urine but no reduction in the glomerular filtration rate. After one year there was a reduction in urine flow as well as in the excretion of both potassium and sodium. Urine osmolality was also reduced. Glomerular filtration rate measured in this group of animals was reduced in the obstructed kidney by about 60% compared to the contralateral one. There were only small changes in the morphology with no loss in parenchymal weight or compensatory hypertrophy, but there was a significant deformation of the papilla and an increase in inflammatory cells in the parenchyma. In conclusion hydronephrosis during a shorter period is not harmful to kidney function but if sustained for an extended time period kidney function will deteriorate.
Animals↗
[Health care in the election. Environmental Party wants a stake in primary health care. Interview by Carina Roxström].
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Delivery of Health Care↗
Pseudoporphyria and sunbeds.
Five cases of pseudoporphyria with recurrent blistering and skin fragility especially of the hands are described. Porphyrin studies were normal. The histopathological investigations in three of these cases showed subepidermal bullae consistent with porphyria cutanea tarda. All patients had considerable sunbed exposure before symptoms appeared. One patient was taking naproxen, a weak photosensitizer.
Adult↗
[104 persons with undiscovered hypertension were found after blood pressure screening by means of a questionnaire].
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Adult↗
Effect of thromboxane inhibition on tubuloglomerular feedback in hydronephrotic kidneys.
The tubuloglomerular feedback (TGF) system is less sensitive after extracellular volume expansion (VE). In rats with partial ureteral obstruction, however, we have previously found increased TGF sensitivity during such expansion. Thromboxane A2 (TXA2) has been reported to be increased in the hydronephrotic kidney, and the present study was undertaken to investigate whether TXA2 might be responsible for these findings. The TGF characteristics were studied, by means of the stop-flow technique, in control and hydronephrotic rats before and after intravenous injection of either a thromboxane synthetase inhibitor or a thromboxane receptor antagonist during hydropenia. After VE, TGF was studied again. Proximal tubular stop-flow pressure (Psf) was measured during perfusion of the loop of Henle with a modified Ringer's solution, the maximal response (delta Psf) to an increased tubular flow rate was determined and the tubular perfusion rate which elicited a half-maximal decrease in Psf, designated the turning point, was recorded. In hydropenic control or hydronephrotic animals, TXA2 did not permanently change the TGF characteristics. During VE of the TXA2-blocked hydronephrotic animals, blocked both with synthetase inhibitor or receptor-antagonist, TGF was reset to a lower sensitivity like VE controls, as indicated by a high turning point and a low delta Psf. It was therefore concluded that thromboxane A2 inhibition does not influence the TGF system in hydropenia, but that the production of thromboxane A2 is responsible for the resetting of the TGF system during VE in hydronephrotic animals.
Animals↗
Back-leak of pelvic urine to the bloodstream.
The aim of the present investigation was to measure the back-leak of pelvic urine to the blood circulation. In normopenic hydronephrotic, dehydrated hydronephrotic and dehydrated control kidneys the back-leak was estimated from a servocontrolled machine which regulated infused saline to keep a present pelvic pressure constant. The disappearance of fluid from the renal pelvis could be measured at different pressure levels, and a pressure-dependent outflow of fluid was found. From these measurements a back-leak conductance could be calculated which proved to be independent of pressure. In the lower pressure range (15-20 mmHg) there was a significantly lower conductance in the dehydrated controls compared with the dyhydrated hydronephrotic kidneys, while in the higher pressure range (25-30 mmHg) no difference was found. From electron microscopical studies the pyelorenal back-leak of fluid in both hydronephrotic and control animals seemed to be most pronounced in the fornix region, as documented by a heavy presence of horseradish peroxidase in the intracellular spaces there. Other experiments with radioactively labelled inulin, which was injected into the pelvic cavity, indicated that most of the back-leak occurred via the renal blood vessels and not through the lymphatic system. The importance of this back-leak was evident from the measurements of the total kidney glomerular filtration rate (GFR) at a slightly increased pelvic pressure, where some of the urine with radioactive tracer flows back to circulation. The back-leak of pelvic urine could also affect the concentration mechanism by removing diluted urine which had flowed over the renal papilla, and through water and urea diffusion increased papillary interstitial osmolarity.
Animals↗
Pressure and flow measurements in the partially obstructed ureter of the rat.
Hydronephrosis in man or experimental animals can be caused by an increased ureteral flow resistance. This condition can in the long run prove harmful to renal function. We compared two ways of measuring ureteral flow resistance in animals with and without a ureteral hindrance, the hindrance being induced by embedding the ureter in the psoas muscle. One needle connected via catheters to a pressure recording system and another connected to a pump system were introduced through the parenchyma into the renal pelvis. Experiments were carried out with two procedures: 1) infusion of 0.5 ml x min-1 of saline into the renal pelvis was performed while recording the pressure response; 2) a servocontrolled pump system was used which regulated the flow introduced into the renal pelvis to keep a preset pressure at a constant level. In the first group of experiments we did not establish a steady-state pressure despite 20-30 min of infusion. The result from the second series of experiments indicated that steady-state flow measurements could be achieved at the different pressure levels between zero and 30 mmHg. A good linear relationship between pressure and flow was found, even though a considerable hysteresis was observed. Furthermore, a reduced flow resistance down to a certain level at increased pressure was also recorded. As expected, the resistance to flow was significantly lower in the control than in the hydronephrotic animals. In order to investigate the diagnostic ability of the linear relationship between pressure and flow, prediction regions for one future animal were calculated. It seemed possible that determination of the whole pressure-flow relationship in the pressure range between zero and 30 mmHg will prove useful to determine the flow hindrance in hydronephrotic animals.
Animals↗
Tubuloglomerular feedback in animals with unilateral, partial ureteral occlusion.
Previous experiments have shown that the sensitivity of the tubuloglomerular feedback system (TGF) is reduced by volume expansion in normal rats. This reduction in sensitivity is probably mediated by changes in the renal interstitial pressure. The present study was designed to investigate the TGF control system during volume expansion in rats with chronic, partial ureteral occlusion--hydronephrosis. Hydronephrosis was induced on the left or right side according to the method described by Ulm and Miller, in weanling Sprague-Dawley rats three weeks old. Three to six weeks later the rats were prepared for whole kidney and micropuncture experiments. Sham-operated animals were used as controls. Net interstitial pressure (that is, interstitial hydrostatic pressure minus interstitial oncotic pressure) was higher in the hydronephrotic, volume expanded animals than in the volume expanded controls. From findings in earlier investigations this increase in interstitial pressure would have been expected to reduce TGF sensitivity but this sensitivity was increased in the hydronephrotic kidneys, as indicated by a reduction in the turning point, the tubular flow rate at which 50% of the maximal stop-flow pressure response was observed (14.4 nl/min, sham-operated control 33.4 nl/min). Strong activity of the TGF mechanism was also indicated by a large proximal-distal difference in the single-nephron glomerular filtration rate (11.9 nl/min versus 3.3 nl/min in sham-operated controls) in the hydronephrotic kidney during volume expansion. Thus, in hydronephrotic kidneys in the latter condition the TGF mechanism was highly sensitive and activated to reduce the glomerular filtration rate. This mechanism may protect the diseased kidney from high intrapelvic pressures which otherwise could damage the kidney during saline volume expansion.
Animals↗
Partial ureteric obstruction in weanling rats. I. Long-term effects on the renal morphology.
Partial obstruction of one ureter was created in weanling rats (3 weeks old) and its effects were studied after 3, 6, and 9 weeks. Within 3 weeks, a considerable hydronephrosis had appeared, which did not progress with time. No effect on parenchymal weight was observed, either on the obstructed side or on the contralateral, intact one. Histological examination revealed a marked deformation of the papilla in about 25% of the hydronephrotic kidneys and evidence of chronic pyelonephritis in 40%. However, the inflammatory changes were restricted to the attenuated circumhilar 'edges' of the parenchyma, thus involving only a minor portion of the kidney. The body weight of the animals obstructed for 9 weeks was 12% lower than that of normal, sham-operated controls. In summary, the effect on the renal parenchyma of partial ureteric obstruction, created in the weanling period, was relatively discrete and less pronounced than when obstruction is performed in the neonatal period.
Animals↗
Tubuloglomerular feedback and interstitial pressure in obstructive nephropathy.
The possible role of the tubuloglomerular feedback (TGF) mechanism in the altered glomerular hemodynamics and tubular reabsorption which occur with prolonged (24-hr) ureteral obstruction and the changes in renal interstitial hydrostatic and oncotic pressure which may modulate TGF sensitivity were examined. The proximal tubule stop-flow pressure (PSF) response to increased distal tubular flow rates (TGF activity) was determined in rats with sham operation, 24-hr unilateral ureteral obstruction (UUO), or 24-hr bilateral ureteral obstruction (BUO), both before and for 2 hr after relief of obstruction. Subcapsular hydrostatic pressure, lymph flow and oncotic pressure, clearance and excretory data were measured in the second series of animals. During and after release of UUO, TGF sensitivity was increased, as indicated by the marked decrease in the loop perfusion rate at which 50% of the maximum decrease in PSF occurred (the turning point of TGF activation). Interstitial oncotic pressure but not hydrostatic pressure was significantly increased in UUO kidneys. In BUO rats, the turning point for TGF activation was slightly higher than the controls and the change in PSF with maximum loop perfusion rates was reduced, indicating a blunting of the TGF response before and particularly during postobstructive diuresis after release of BUO. Interstitial hydrostatic and oncotic pressures were both slightly increased resulting in no changes in net interstitial Starling forces. We conclude that enhanced TGF sensitivity after release of prolonged UUO, associated with increased interstitial oncotic pressure, may play a role in preventing postobstructive diuresis, while the blunting of TGF sensitivity after BUO may contribute to this phenomenon.
Animals↗
Effect of surgical trauma on plasma insulin and somatostatin in response to glucose.
The role of somatostatin for the suppression of insulin release in the early post-traumatic phase was investigated by measurement of somatostatin-like immunoreactivity in plasma during an intravenous glucose tolerance test. In accordance with previous findings the increase of insulin in response to glucose was significantly (p less than 0.001) reduced 2 hours after laparotomy as compared to control subjects. Simultaneously plasma somatostatin was decreased significantly (p less than 0.05). The present data with hormone determinations in peripheral blood does not support the hypothesis that somatostatin, a potent inhibitor of insulin release, mediates the insulin suppression in the early trauma phase.
Adult↗
Reduction of androstenedione by skin in vitro and serum levels of gonadotrophins and androgens in men with hypospadias.
The reduction of 4-[1,2-3H]androstene-3,17-dione (androstenedione) in vitro by scrotal skin was measured in samples from nine men (16--34 years old) with hypospadias and from ten male control subjects. The reduction of androstenedione was also studied in axillary and upper arm skin of seven control subjects. Androstenedione was reduced to material with chromatographic characteristics of 5 alpha-androstane-3,17-dione and to 3 alpha- and 3 beta-hydroxy-5 alpha-androstan-17-one. No difference in 5 alpha-reductase activity (defined as the sum of these three metabolites formed) was found in scrotal skin from hypospadic and control men. The mean concentration of 5 alpha-dihydrotestosterone in serum from men with hypospadias was lower than that in serum from control subjects (P less than 0.01). The mean ratio of the serum concentrations of testosterone and 5 alpha-dihydrotestosterone was higher in hypospadic men than in control subjects (P less than 0.05). No differences between the two groups were found in the mean serum concentrations of LH, FSH, prolactin, dehydroepiandrosterone, androstenedione, testosterone or testosterone-binding globulin.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
The metabolism of 4-androstene-3,17-dione by isolated rat hepatocytes. Maintenance of the sex differences in culture.
Hepatocytes from adult rats were isolated and cultivated as primary monolayers for 3 days in a medium containing only 1% homologous serum. The metabolism of 4-androstene-3,17-dione was followed in hepatocytes from male, female and hypophysectomized animals. It was found that immediately after preparation, 5alpha-reductase and 16alpha-hydroxylase activities were present in the cells in amounts comparable to those found in microsomal preparations from liver homogenates. After 3 days in culture, these enzyme activities had decreased to about half the values measured on day 0. During this time the sexual differences in steroid metabolism in the cells were stable, i.e. there was no detectable induction of 16alpha-hydroxylase in cells from female animals, and the relative sex difference in 5alpha-reductase activity persisted.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗