Cerebral activation during micturition in normal men.
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Specific cerebral lesions have shown the crucial role of the brain in the control of micturition. The precise identification of the anatomical cerebral structures involved in micturition can contribute to a better understanding of the control of micturition and the development of therapeutic models. Various neuropathological and animal studies have referred to the medulla oblongata, pons, limbic system, superior frontal lobe and premotor cortical regions as areas implicated in micturition control. The aim of this study was to investigate whether the activity of these areas during micturition can be confirmed by PET in normal men. The distribution of the regional cerebral blood flow after bolus injection of (15)O water was used as an indirect measure of cerebral activation. PET scans were performed during the following three conditions: (i) at rest with the bladder empty; (ii) during simulated micturition after instillation of isotonic saline into the urinary bladder; and (iii) the withholding of urine (saline). Normal micturition using this model was achieved in eight out of 12 right-handed normal subjects. The changes in bladder contraction, bladder pressure and intra-abdominal pressure were monitored on-line during the whole scanning session by a cystometry device. The images were analysed using statistical parametric mapping at a significance threshold of P < 0.05 with correction for multiple independent comparisons. Micturition versus rest was associated with bilateral activation of areas close to the postcentral gyrus, inferior frontal gyrus, globus pallidus, cortex cerebelli, vermis and midbrain. On the left side, activation of the middle frontal gyrus, superior frontal gyrus, superior precentral gyrus, thalamus and the caudal part of the anterior cingulate gyrus was seen, while on the right side we found activation in the supramarginal gyrus, mesencephalon and insula. When the threshold value was lowered to P < 0.001 (Z > 3.09) without correction for multiple comparisons, we found additional activation in the medial pontine tegmentum, mesencephalon, right thalamus, right middle frontal gyrus and left insula. When urine- withholding was compared with rest, the left insula showed a tendency to activate. We conclude from this study, in which urinary bladder contraction was verified cystometrically, that the onset and maintenance of micturition in normal men is associated with a vast network of cortical and subcortical regions, confirming observations from clinical and animal studies. (+info)
Pharmacological evaluation of the role of cyclooxygenase isoenzymes on the micturition reflex following experimental cystitis in rats.
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Prostanoids, generated from cyclooxygenase (COX) isoenzymes, play a role in the physiological function of the lower urinary tract and are important mediators of inflammatory hyperalgesia. The present work evaluates the effects of the COX-1/COX-2 inhibitor dexketoprofen as well as of a selective COX-2 inhibitor, NS-398, on urodynamic function following endotoxin (LPS) or cyclophosphamide (CYP)-induced inflammation of the urinary bladder. The application of arachidonic acid (330 microgram rat(-1)) onto the serosal surface of the urinary bladder in control rats elicited bladder contractions which could be blocked in a dose-dependent manner by dexketoprofen (0.1 - 3 mg kg(-1), i.v.) but not by NS-398 (0.2 - 6 mg kg(-1), i.v. ). Dexketoprofen (3 mg kg(-1), i.v.) decreased the micturition frequency and increased the pressure threshold for triggering the micturition either when administered within 15 min or 3 h following surgery in control animals. NS-398 (6 mg kg(-1), i.v.) decreased the micturition frequency and increased the pressure threshold when administered 3 h but not 15 min following surgery. Administration of LPS (2 mg kg(-1), i.v., 90 - 120 min) increased both the micturition frequency and the pressure threshold for triggering the micturition reflex. Changes in urodynamic parameters induced by LPS were prevented by doses of either dexketoprofen (1 mg kg(-1), i.v.) or NS-398 (2 mg kg(-1), i.v.) which were ineffective in control animals. Pretreatment with CYP (150 mg kg(-1), i.p., 48 h) increased the micturition frequency, pressure threshold, and the minimal intravesical pressure but decreased the mean amplitude of micturition contractions. In CYP-treated rats, dexketoprofen (1 mg kg(-1), i.v.) or NS-398 (2 mg kg(-1), i.v.) blocked the CYP-induced urodynamic changes with exception of the micturition contraction amplitude. These results indicate that COX-1 may be involved in modulating the threshold for activating the micturition reflex in the normal rats and also demonstrates that inhibition of COX-2 prevents or reverses the urodynamic changes associated with bladder inflammation induced either by surgery, LPS or CYP treatments. (+info)
Reduction in renal haemodynamics by exaggerated vesicovascular reflex in rats with acute urinary retention.
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1. We examined the possibility that a vesicovascular reflex is exaggerated by acute urinary retention, and that the increase in renal vascular resistance caused by this reflex may lead to renal dysfunction. We evaluated the vesicovascular responses to normal micturition (NM, transcystometric condition) and acute urinary retention (isovolumetric condition mimicking complete bladder-outlet obstruction (CBOO) and partial urethral ligation mimicking partial bladder-outlet obstruction (PBOO)) in anaesthetized female Wistar rats. 2. Acute urinary retention due to CBOO or PBOO provoked a prolonged or increased intravesical pressure, an enhancement in both bladder pelvic afferent and bladder pelvic efferent nervous activity, and an elevation in mean arterial blood pressure. 3. Single-unit analysis showed that these vesicovascular reflexes were triggered by activation of low-threshold and high-threshold bladder mechanoreceptors, but not by renal uretropelvic mechanoreceptors. 4. Bladder contraction in CBOO and PBOO conditions and graded increases in bladder volume significantly reduced renal blood flow and cortical microvascular blood flow. The acute urinary retention-induced renal vasoconstriction was mediated by the renal nerve. Renal denervation, but not bilateral ureteral resection, abolished the renal vasoconstriction associated with the vesicovascular reflexes. 5. These findings indicate that exaggerated activation of bladder afferents exerts a positive feedback effect to increase sympathetic outflow to the kidney further, thereby contributing to significant renal vasoconstriction via a renal nerve-dependent mechanism. (+info)
Comparison of enalapril and valsartan in cyclosporine A-induced hypertension and nephrotoxicity in spontaneously hypertensive rats on high-sodium diet.
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1. We compared the effects of the angiotensin converting enzyme (ACE) inhibitor enalapril and the angiotensin AT(1) receptor antagonist valsartan in cyclosporine A (CsA)-induced hypertension and nephrotoxicity in spontaneously hypertensive rats (SHR). 2. SHR (8 - 9 weeks old) on high-sodium diet were given CsA (5 mg kg(-1)d (-1) s.c. ) for 6 weeks. The rats were treated concomitantly either with enalapril (30 mg kg(-1)d (-1) p.o.) or valsartan (3 or 30 mg kg(-1) d (-1) p.o.). To evaluate the role of bradykinin in the action of enalapril, some rats received a bradykinin B(2) receptor antagonist icatibant (HOE 140, 500 microg kg(-1) d (-1) s.c.) during the last 2 weeks of enalapril treatment. 3. Blood pressure was recorded every second week by tail cuff method. Renal function was measured by serum creatinine, creatinine clearance and urinary excretion of proteins at the end of the experiment. The activity of the renal kallikrein-kinin system was estimated by urinary kallikrein excretion. 4. CsA caused hypertension, impaired renal function and induced morphological nephrotoxicity with glomerular damage and interstitial fibrosis. Enalapril and the lower dose of valsartan attenuated the CsA-induced hypertension to the same extent, while the higher dose of valsartan totally abolished it. Icatibant did not reduce the antihypertensive effect of enalapril. Urinary kallikrein excretion was similar in all groups. 5. Enalapril and valsartan equally prevented the CsA-induced deterioration of kidney function and morphology. 6. The renin-angiotensin but not the kallikrein-kinin system plays a crucial role in CsA-toxicity during high intake of sodium in SHR. (+info)
Use of radionuclide imaging in the early diagnosis and treatment of renal allograft rejection.
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Data are presented on the clinical application of radionuclide imaging to evaluate changes in cadaver transplant function in the immediate postoperative period. The method uses orthoiodohippuric acid (hippuran) administered IV, with scintillation imaging, and curve analysis by a digital computer. An initial study is always obtained 24 hours after transplantation. Serial studies are then obtained, as needed, to interpret the clinical course. Selected cases are presented which illustrate the use of this protocol in various clinical settings. In the oliguric patient serial studies have been of particular value. They have identified ATN so that over-enthusiastic treatment for rejection could be avoided. They have also identified acute rejection complicating ATN so that high dose steroid therapy could be administered appropriately. In the non-oliguric patient they have frequently contributed to the early diagnosis of acute rejection, and they have been useful in monitoring the effect and duration of treatment for severe rejection crisis. It is concluded that radionuclide imaging studies, when carefully applied and interpreted, are a valuable adjunct to the management of patients in this complex clinical setting. (+info)
Human atrial natriuretic peptide infusion for a neonate with congestive heart failure after total correction of total anomalous pulmonary venous connection.
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A successful case of human atrial natriuretic peptide (HANP) infusion therapy for a neonate who developed congestive heart failure (CHF) after total repair of total anomalous pulmonary venous connection was performed on the first day of life. Following 14h of HANP infusion at incremental doses of 0.125-0.25 microg x kg(-1) x min(-1) urine output and hemodynamics dramatically improved. Urine output increased from 1.1 to 10.6 ml/h (p<0.0001) and good urinary output (13.0 ml/h) was maintained even after discontinuation of the infusion. During the infusion, the heart rate decreased from 166 to 152 beats/min (p<0.0001), and the systemic systolic blood pressure increased from 82 to 103 mmHg (p<0.0001). Central venous pressure was not significantly affected by HANP infusion. This is the first successful case of HANP infusion therapy as the first treatment of post-operative pulmonary hypertension in this age group. This therapy can be used safely and may be useful in neonates with CHF resulting from other causes, but more investigation is needed. (+info)
A double-blind, placebo-controlled study to assess tolerability, pharmacokinetics and preliminary pharmacodynamics of single escalating doses of Z13752A, a novel dual inhibitor of the metalloproteases ACE and NEP, in healthy volunteers.
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AIMS: The objective of this study was to evaluate the tolerability of a novel dual ACE-NEP inhibitor, Z13752A, after the oral administration of rising single doses in healthy volunteers. This study was also a preliminarily investigation of Z13752A pharmacodynamics (PD) and pharmacokinetics (PK). METHODS: In this randomized, placebo-controlled, sequential study, two alternating panels of eight healthy male volunteers each (six subjects receiving the active treatment + two subjects receiving placebo) were treated with increasing oral doses of Z13752A: 10, 50, 200, and 600 mg were given to panel I and 20, 100, 400 and 800 mg were given to panel II. The study was double-blind relative to placebo or active treatment, and was open with respect to the dose levels. The same volunteer received placebo only once. RESULTS: Single oral doses of Z13752A, as high as 800 mg, were well tolerated. Only six mild-to-moderate adverse events mainly headache, were reported and appeared to be of little clinical relevance. After administration of 200, 400, 600 and 800 mg of Z13752A, a nonsignificant fall in diastolic blood pressure was detected, in both the standing and supine position. After single oral doses of Z13752A, ACE inhibition appeared to be significant at all the doses tested, linearly correlated with the dose and was almost complete at doses > or = 100-200 mg. NEP inhibition was indicated by elevation of ANP and cGMP plasma concentrations in almost all subjects. In the 200-800 mg dose range, Z13752A produced a 50-100% increase of plasma cGMP levels and a 50-80% elevation in urinary cGMP concentrations. Detectable plasma levels of Z13752A were found in all the treated subjects. Z13752A was well and rapidly absorbed, with peak concentrations reached approximately 2.5 h after administration. The mean apparent elimination half-life from plasma was approximately 12 h. The pharmacokinetics of Z13752A after single oral doses were characterized by low intersubject variability and appeared to be dose-independent. CONCLUSIONS: Z13752A showed a good single dose tolerability profile at doses up to 800 mg. The pharmacokinetic data indicate that Z13752A administered orally is rapidly absorbed and available to the systemic circulation in humans. The relatively slow clearance indicates that a once-a-day dose regimen could be considered for Z13752A. (+info)
Cognitive behavioral and behavioral interventions help young children cope during a voiding cystourethrogram.
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OBJECTIVE: To reduce young children's distress and increase coping behavior among children undergoing a voiding cystourethrogram (VCU). METHODS: Three- to seven-year-old children were stratified based on prior VCU experience and randomly assigned to an intervention (n = 20) or a standard care (n = 20) condition. The intervention included provision of information, coping skills training, and parent coaching. We hypothesized that the intervention would reduce children's distress as assessed by child report, parent and technician ratings, and behavioral observations. RESULTS: Children in the intervention displayed fewer distress behaviors and greater coping behaviors and were rated as more cooperative than children receiving standard care. Children's fear and pain ratings did not differ significantly between groups. CONCLUSIONS: A cognitive-behavioral treatment package effectively reduced children's distress, increased coping, and increased cooperation during voiding cystourethrogram procedures. This type of an intervention should be integrated into routine pediatric radiological procedures. (+info)