Nitric oxide metabolites, eosinophils, and eosinophilic cationic protein in patients with asthma: sputum versus blood.

The monitoring of airway inflammation has assessed in bronchial asthma directly by sputum examination, and indirectly by measurements in peripheral blood. To investigate the diagnostic value of these two methods, we compared nitric oxide (NO) metabolites, eosinophils, and eosinophil cationic protein (ECP) in sputum and blood in patients with asthma and control subjects. Sputum and serum were obtained from fifteen patients with asthma, and then were examined before anti-asthma treatment, including steroid preparations. ECP was measured by fluoroimmunoassay. NO metabolites were assayed by using modified Griess reaction. Asthmatic patients, compared with control subjects, had significantly higher level of NO metabolites, higher proportion of eosinophils, and higher levels of ECP in sputum. Asthmatic patients, compared with control subjects, however, had significantly higher number of eosinophils, and were at higher levels of ECP in blood. FEV1, FEV1/FVC was negatively correlated with sputum eosinophils. The area under receiver operating characteristic (ROC) curve showed that eosinophils in sputum are significantly accurate markers than NO metabolites in sputum and blood. These findings suggest that the proportion of eosinophils in sputum have more accurate diagnostic marker of asthmatic airway inflammation than NO metabolites in sputum in differentiating asthmatic patients from control subjects.

Diminished expression of aquaporin water channels in ureteral-obstructed kidney in rats.

OBJECTIVE: We investigated whether regulation of aquaporin (AQP) water channels is altered in the ureteral-obstructed kidney. MATERIAL AND METHODS: Male Sprague-Dawley rats were unilaterally obstructed of their left proximal ureters for 48 h. The protein expression of AQP1-3 channels was determined in the kidney by Western blot analysis. The expression of AQP2 was also determined by immunohistochemistry. In order to specifically determine primary impairment of the pathway leading to an altered regulation of AQP channels stimulated by the arginine vasopressin (AVP)/cyclic adenosine monophosphate (cAMP) pathway, the catalytic activity and protein expression of different parts of the adenylyl cyclase complex were separately determined. RESULTS: In the previously obstructed kidney, urinary osmolality and free water reabsorption were greatly decreased. The expression of AQP2 proteins was decreased in the cortex, outer medulla and inner medulla. Immunohistochemistry also showed a marked decrease in AQP2 expression. The expression of AQP1 and AQP3 was decreased in the outer medulla and inner medulla. cAMP generation in response to AVP, sodium fluoride or forskolin was greatly decreased. The expression of Gsalpha and adenylyl cyclase VI proteins was decreased. The contralateral kidney showed minimal or no changes in these parameters. CONCLUSIONS: The reduced abundance of AQP water channels may at least partly account for the urinary concentration defect in the ureteral-obstructed kidney. The primary point of impairment of AQP channels regulated by the AVP/cAMP pathway may lie at the level of the catalytic unit of adenylyl cyclase.

Airway obstruction after acute ozone exposure in BALB/c mice using barometric plethysmography.

BACKGROUND: Airway responsiveness after acute inhalation of ozone is related to the concentration and duration of ozone exposure. Using barometric whole-body plethysmography and increase in enhanced pause (Penh) as an index of airway obstruction, we measured the response of BALB/c mice to acute ozone inhalation to study the time course change of pulmonary function after ozone exposure. METHODS: Penh was measured before and after exposure to filtered air or 0.12, 0.5, 1, or 2 ppm ozone for 3 hr (n = 6/group). In addition, Penh was measured 24, 48 and 72 hr after ozone exposure. Bronchoalveolar lavage (BAL) and histopathologic examinations were performed. RESULTS: The increase in Penh after ozone exposure was significantly higher in the 0.12, 0.5, 1 and 2 ppm groups compared with the control group (all p < 0.01). Increases in Penh 24 hr after ozone exposure were significantly lower than those immediately after acute ozone exposure; however, increases in Penh 72 hr after ozone exposure were significantly higher than those in the control group (each p < 0.01). The proportion of neutrophils in BAL fluid was significantly higher in the group exposed to 2 ppm ozone than in the groups exposed to filtered air or 0.12 ppm ozone (both p < 0.01). CONCLUSION: These results indicate that airway obstruction is induced following ozone exposure in a concentration-dependent manner and persists for at least 72 hr.

Unilateral autosomal dominant polycystic kidney disease with contralateral renal agenesis: a case report.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease. There are some reports in the literature concerning unilateral ADPKD. However, in adults, only a few cases of unilateral ADPKD with agenesis of contralateral kidney have been reported. We present a case of unilateral ADPKD with agenesis of contralateral kidney in a 66-yr-old man. Radiographic images showed the enlarged right kidney with multiple variable-sized cysts and the absence of the left kidney. The diagnosis of ADPKD was confirmed by the family screening. The patient received maintenance hemodialysis for endstage renal disease. We report a case of unilateral ADPKD associated with contralateral renal agenesis in a 66-yr-old male patient with a literature review.

Increased expression of aquaporin water channels in hypothyroid rat kidney.

The present study was aimed to determine the molecular mechanisms underlying the water retention associated with hypothyroidism. Male Sprague-Dawley rats (200-220g) were experimentally induced of hypothyroidism by treatment with methimazole in drinking water (0.04%) for 8 weeks. In the experimental group, serum concentrations of thyroxine and triiodothyronine were significantly decreased. The expression of aquaporin 2 (AQP2) was significantly increased in the cortex, outer medulla, and inner medulla of the kidney. The expression of AQP1 as well as that of AQP3 was significantly increased in the cortex, though not in the medulla. The adenylyl cyclase activity provoked by arginine vasopressin (AVP), sodium fluoride, or forskolin was blunted in the hypothyroid kidney, while plasma levels of AVP were not significantly changed. The increased expression of AQP1-3 channels may in part account for the water retention in hypothyroidism.

Attenuated renal excretion in response to thiazide diuretics in Gitelman's syndrome: a case report.

Gitelman's syndrome is a variant of Bartter's syndrome characterized by hypocalciuria and hypomagnesemia. The administration of thiazide diuretics may induce a subnormal increase of urinary Na+ and Cl- excretion in patients with Gitelman's syndrome, consistent with the hypothesis that less Na+ and Cl- than normal is reabsorbed by the thiazide-inhibitable transporter in Gitelman's syndrome. Specific mutations of NaCl cotransporter, coupled with mutant NaCl cotransporter expression studies clearly demonstrated that many of the characteristics of individuals with Gitelman's syndrome are explained by lack of function of NaCl cotransporter. We recently diagnosed a patient with Gitelman's syndrome by performing the thiazide and furosemide tests, and it is suggested that the clearance studies by diuretic administration may be of diagnostic help in Gitelman's syndrome.

Diminished renal expression of aquaporin water channels in rats with experimental bilateral ureteral obstruction.

Whether postobstructive diuresis could be related to altered regulation of aquaporin (AQP) water channels in the kidney was investigated. Male Sprague-Dawley rats underwent bilateral obstruction of the proximal ureters for 48 h. The renal expression of AQP1 to AQP4 proteins was then determined by Western blot and immunohistochemical analyses. For elucidation of the primary impairment in the upstream pathway leading to the expression of cAMP-mediated AQP channels, the expression of G(salpha) and that of adenylyl cyclase were also determined. For some rats, the obstruction was released for collection of urine samples. After the ureteral obstruction, the urinary flow rate was increased and free water reabsorption was decreased. In the obstructed kidneys, the expression of AQP1 to AQP3 was decreased in the cortex, outer medulla, and inner medulla, whereas that of AQP4 was decreased in the inner medulla. Immunoreactivities for AQP1 to AQP4 were also decreased in the obstructed kidneys. The protein expression of G(salpha) was decreased in the cortex, outer medulla, and inner medulla, whereas that of adenylyl cyclase VI was decreased in the outer and inner medullae. cAMP generation stimulated by arginine vasopressin was decreased in the cortex, outer medulla, and inner medulla. cAMP generation in response to forskolin was decreased in the outer and inner medullae, whereas that in response to sodium fluoride was decreased in the cortex, outer medulla, and inner medulla. These results suggest that a reduced abundance of AQP water channels in the kidney accounts in part for postobstructive diuresis. The primary impairment of AQP channels that are regulated via the arginine vasopressin/cAMP pathway may lie at the level of G proteins and adenylyl cyclase itself.