Correlates of urinary symptom scores in men.
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OBJECTIVES: This study determined the prevalence of urinary symptoms and their relationship to characteristics of a cohort of men in Beaver Dam, Wis, from 1993 to 1995. METHODS: A standardized questionnaire concerning urinary symptoms (the American Urological Association Urinary Symptom Questionnaire) was administered. RESULTS: All outcomes were associated with age and history of enlarged prostate. Urinary frequency (57%) and nocturia (65%) were the most common individual symptoms. Diuretic usage, diabetes, history of cardiovascular disease, and smoking were related to specific symptoms. CONCLUSIONS: While urinary symptoms are associated with age and history of enlarged prostate, symptoms may also be attributable to other diseases and exposures. (+info)
Alveolar epithelial fluid transport can be simultaneously upregulated by both KGF and beta-agonist therapy.
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Although keratinocyte growth factor (KGF) protects against experimental acute lung injury, the mechanisms for the protective effect are incompletely understood. Therefore, the time-dependent effects of KGF on alveolar epithelial fluid transport were studied in rats 48-240 h after intratracheal administration of KGF (5 mg/kg). There was a marked proliferative response to KGF, measured both by in vivo bromodeoxyuridine staining and by staining with an antibody to a type II cell antigen. In controls, alveolar liquid clearance (ALC) was 23 +/- 3%/h. After KGF pretreatment, ALC was significantly increased to 30 +/- 2%/h at 48 h, to 39 +/- 2%/h at 72 h, and to 36 +/- 3%/h at 120 h compared with controls (P < 0.05). By 240 h, ALC had returned to near-control levels (26 +/- 2%/h). The increase in ALC was explained primarily by the proliferation of alveolar type II cells, since there was a good correlation between the number of alveolar type II cells and the increase in ALC (r = 0.92, P = 0.02). The fraction of ALC inhibited by amiloride was similar in control rats (33%) as in 72-h KGF-pretreated rats (38%), indicating that there was probably no major change in the apical pathways for Na uptake in the KGF-pretreated rats at this time point. However, more rapid ALC at 120 h, compared with 48 h after KGF treatment, may be explained by greater maturation of alpha-epithelial Na channel, since its expression was greater at 120 than at 48 h, whereas the number of type II cells was the same at these two time points. beta-Adrenergic stimulation with terbutaline 72 h after KGF pretreatment further increased ALC to 50 +/- 7%/h (P < 0.5). In summary, KGF induced a sustained increase over 120 h in the fluid transport capacity of the alveolar epithelium. This impressive upregulation in fluid transport was further enhanced with beta-adrenergic agonist therapy, thus providing evidence that two different treatments can simultaneously increase the fluid transport capacity of the alveolar epithelium. (+info)
Hypoxia reduces airway epithelial sodium transport in rats.
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Ascent to high altitude leads to pulmonary edema formation in some individuals. Recent laboratory evidence supports the hypothesis that hypoxia may impair the function of the alveolar epithelium and thus augment edema accumulation via reduced clearance of lung liquid. We investigated the effect of hypobaric hypoxia on epithelial sodium transport in adult Sprague-Dawley rats by measuring the nasal transepithelial potential difference (PD) as an index of airway sodium transport. Baseline PDs were similar to those previously reported in other species. Administration of amiloride resulted in a significant fall in nasal PD, as did ouabain administration for 24 h (-27.8 vs. -18.8 mV; P = 0.001; n = 5 rats). Exposure to hypobaric hypoxia (0.5 atm) for 24 h caused a significant fall in nasal PD (-23.7 vs. -18.8 mV; P = 0.002; n = 15 rats), which was not additive to the changes in nasal PD produced by amiloride or ouabain. We conclude that subacute exposure to moderate hypobaric hypoxia can inhibit sodium transport by the airway epithelium in rats. (+info)
Antiproliferative effects of NO and ANP in cultured human airway smooth muscle.
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Airway smooth muscle (ASM) hypertrophy and hyperplasia are important determinants of bronchial responsiveness in asthma, and agents that interfere with these processes may prevent airway remodeling. We tested the hypothesis that activators of soluble and particulate guanylyl cyclases would inhibit human ASM cell (HASMC) proliferation. We report that the nitric oxide (NO) donors S-nitroso-N-acetylpenicillamine (SNAP; 10(-6) to 10(-4) M) and sodium nitroprusside (10(-5) to 10(-3) M) and human atrial natriuretic peptide [ANP-(1-28); 10(-8) to 10(-6) M], which activate soluble and particulate guanylyl cyclases, respectively, inhibited serum- and thrombin-induced proliferation of cultured HASMCs. The antimitogenic effect of SNAP was reversed by hemoglobin (10(-5) M), an NO scavenger, suggesting that NO donation was involved. The antiproliferative effects of SNAP and ANP-(1-28) were potentiated by the cGMP-specific phosphodiesterase zaprinast and mimicked by 8-bromo-cGMP (10(-6) to 10(-3) M), suggesting that cGMP-dependent mechanisms were involved. However, first, ANP-(1-28) produced a smaller antiproliferative effect than SNAP in contrast to their abilities to elevate cGMP, and second, rat ANP-(104-126), which binds selectively to ANP clearance receptors without elevating cGMP, had a small antiproliferative effect, suggesting that cGMP-independent mechanisms were also involved. These results provide evidence for a novel antiproliferative effect of NO and ANP in HASMCs mediated through cGMP-dependent and cGMP-independent mechanisms. (+info)
Thiazide induces water absorption in the inner medullary collecting duct of normal and Brattleboro rats.
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The reduction of urinary volume after the use of thiazide in the treatment of diabetes insipidus (DI) is known as the "paradoxical effect." Since enhanced proximal solute and water reabsorption only partially account for the reduction in urinary volume, an additional diuretic effect on nephron terminal segments was postulated. Thus the aim of our work was to investigate the effect of hydrochlorothiazide (HCTZ) on water transport in the inner medullary collecting duct (IMCD) of normal and Brattleboro rats. Osmotic water permeability (P(f)) and diffusional water permeability (P(dw)) were studied at 37 degrees C and pH 7.4 by the in vitro microperfusion technique. In the absence of antidiuretic hormone (ADH), HCTZ (10(-6) M) added to the perfused fluid enhanced P(f) from 6.36 +/- 0. 56 to 19.08 +/- 1.70 micro(m)/s (P < 0.01) and P(dw) from 38.01 +/- 4.52 to 52.26 +/- 4.38 x10(-5) cm/s (P < 0.01) in normal rats and also stimulated P(f) in Brattleboro rats from 3.53 +/- 1.41 to 11.16 +/- 1.13 micro(m)/s (P < 0.01). Prostaglandin E(2) (PGE(2)) (10(-5) M) added to the bath fluid inhibited HCTZ-stimulated P(f) (in micro(m)/s) as follows: control, 16.93 +/- 2.64; HCTZ, 29.65 +/- 5.67; HCTZ+PGE(2), 10.46 +/- 1.84 (P < 0.01); recovery, 16.77 +/- 4.07. These data indicate that thiazides enhance water absorption in IMCD from normal rats (in the absence of ADH) and from Brattleboro rats and that the HCTZ-stimulated P(f) was partially blocked by PGE(2). Thus we may conclude that the effect of thiazide in the treatment of DI occurs not only in the Na(+)-Cl(-) cotransport in the distal tubule but also in the IMCD. (+info)
F+0 diuresis renography in infants and children.
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The purpose of this study was to evaluate the feasibility of modifying diuresis renography by the simultaneous administration of 99mTc-mercaptoacetyltriglycine (MAG3) and furosemide in the investigation of hydronephrosis and hydroureteronephrosis in infants and children. Two parameters were assessed: the diuretic response in normal kidneys and the ability of the F+0 study to differentiate between renal obstruction and nonobstruction and to identify the level of obstruction in cases of renal obstruction. METHODS: Seventy-two patients (48 males, 24 females; age 2 d to 7 y; median age 6 wk) with sonographic diagnoses of hydronephrosis or hydroureteronephrosis were reviewed prospectively over a 3-y period. All patients had prior sonographic studies and micturating cystourethrography. Bladder catheterization was not routinely performed and was undertaken only if the child had suspected vesicoureteric junction (VUJ) obstruction or grade II or more vesicoureteric reflux. A weight-adjusted dose of 99mTc-MAG3 (maximum 200 MBq, minimum 20 MBq) and 1 mg/kg of furosemide (maximum 40 mg) were administered intravenously at the same time. Posterior imaging of the kidneys and bladder was performed for 20 min and followed by gravity-assisted drainage or imaging after voiding. All patients were followed-up for 6-12 mo, and the final diagnoses were based on either surgery or conservative management with repeated sonography or follow-up 99mTc-MAG3 studies (or both). The results of the F+0 diuresis renography were then compared with the final diagnoses. RESULTS: A renal unit was defined as a kidney and its ureter. There were 151 renal units with 1 patient having bilateral duplex kidneys, 6 patients having unilateral duplex kidneys and 1 patient having a solitary kidney. Fifty-five normal renal units and 96 abnormal renal units on the basis of sonographic findings were assessed. The furosemide clearance half-time for the 55 normal renal units was 1.3-6.3 min (mean 3.8 min). Of the 96 abnormal renal units, 53 were classified as nonobstructed and 43 were classified as obstructed. Of the 53 renal units classified as nonobstructed, there were 48 true-negative studies and 5 false-negative studies; of the 43 renal units classified as obstructed, there were 40 true-positive studies and 3 false-positive studies. The sensitivity was 88.9%, specificity was 94.1% and accuracy was 91.7%. The level of obstruction, either pelviureteric junction or VUJ, was also correctly identified. CONCLUSION: F+0 diuresis renography shows excellent diuretic responses in normal kidneys and is a valid method for the investigation of hydronephrosis and hydroureteronephrosis in infants and children. (+info)
Studies were carried out to determine the intrarenal adenosine production during hypoxia, and the protective effects of a selective adenosine A(1) receptor antagonist 8-(noradamantan-3-yl)-1, 3-dipropylxanthine (KW-3902) on hypoxia-induced renal hemodynamic changes. We used an in vivo microdialysis method and measured the renal interstitial concentration of adenosine in response to hypoxic exposure in anesthetized mechanically ventilated rabbits. Normocapnic systemic hypoxia (PaO(2) = 32 +/- 6 mm Hg) caused a significant decrease in renal blood flow and increase in renal vascular resistance, indicating a renal vasoconstriction. The basal interstitial concentration of adenosine in the cortex was 293 +/- 70 nM, which was significantly higher than that in the medulla (170 +/- 23 nM). Five minutes after beginning hypoxia, the renal interstitial concentration of adenosine approximately tripled in the cortex and doubled in the medulla. During treatment with KW-3902, hypoxemia caused a similar increase in the adenosine concentration compared with that in the absence of KW-3902. The administration of KW-3902, however, significantly attenuated hypoxia-induced reduction in renal blood flow. These results suggest that adenosine was involved in hypoxia-induced renal vasoconstriction via its effects on adenosine A(1) receptors, and that KW-3902 had a partial protective effect against renal vasoconstriction during hypoxemia. (+info)
Uptake and glutathione conjugation of ethacrynic acid and efflux of the glutathione adduct by periportal and perivenous rat hepatocytes.
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We assessed the impact of zonal factors on the hepatic reduced glutathione (GSH) conjugation of ethacrynic acid (EA). Uptake of EA by enriched periportal (PP) and perivenous (PV) rat hepatocytes was characterized by both saturable (V(max)(uptake) = 3.4 +/- 1.7 and 3. 2 +/- 0.8 nmol/min/mg protein and K(m)(uptake) = 51 +/- 13 and 44 +/- 15 microM) and nonsaturable (12 +/- 5 and 12 +/- 3 microl/min/mg protein) components. Values for the overall GSH conjugation rates of EA (200 microM) were similar among the zonal hepatocytes and resembled those for the influx transport rates. In the absence of the hepatocyte membrane, GSH conjugation in PV and PP hepatocyte cytosol was similar, but a higher perivenous GSH conjugation activity toward EA (PV/PP of 2.4) that mirrored the higher PV/PP ratios of immunodetectable GSTs Ya (1.7) and Yb2 (2.5) was found in cell lysates obtained by the dual-digitonin-pulse perfusion technique. The GSH conjugation rates in the subcellular fragments were, however, much greater than those observed for intact hepatocytes. Efflux rates of the glutathione conjugate EA-SG from zonal hepatocytes were similar, as were levels of the immunodetectable multidrug-resistance protein 2/canalicular multispecific organic anion transporter (Mrp2/cMoat) in the 100,000g pellets. The composite results suggest that the GSTs responsible for EA metabolism are more abundant in the PV region, albeit that the gradient of enzymatic activities is shallow. Despite the existence of zonal metabolic activity, the overall GSH conjugation rate of EA is homogeneous among cells because the reaction is rate limited by uptake, which occurs evenly. Results on EA-SG efflux suggest the acinar homogeneity in Mrp2/cMoat function for canalicular transport. (+info)