Urodynamic risk factors for renal dysfunction in men with obstructive and nonobstructive voiding dysfunction

BACKGROUND AND PURPOSE: Adrenomedullin is a recently discovered vasoactive peptide that is structurally related to calcitonin gene-related peptide (CGRP). Adrenomedullin is produced by vascular endothelium and smooth muscle and is present in the brain. The goals of this study were to determine (1) whether adrenomedullin produces dilatation of cerebral arterioles and whether this effect is mediated by activation of CGRP receptors and (2) whether vasodilatation to adrenomedullin was mediated by K+ channels. METHODS: Diameter of cerebral arterioles (mean +/- SE baseline, 46 +/- 1 microns) was measured using a closed cranial window in anesthetized rats. RESULTS: Application of rat adrenomedullin (10(-7) and 10(-6) mol/L) increased vessel diameter by 16 +/- 3% and 45 +/- 8% (n = 5), respectively. Vasodilator responses to repeated application of adrenomedullin were reproducible. Pretreatment of cerebral arterioles with the specific CGRP1 receptor antagonist CGRP-(8-37) (5 x 10(-7) mol/L) selectively inhibited the vasodilator responses to adrenomedullin without inhibiting responses to ADP (10(-5) to 10(-3) mol/L). Responses to adrenomedullin (10(-7) and 10(-6) mol/L) were 14 +/- 1% and 40 +/- 3% before and 2 +/- 2% and 6 +/- 1% after CGRP-(8-37), respectively (P < .01). Glibenclamide (10(-6) mol/L), an inhibitor of ATP-sensitive K+ channels, reduced the responses to adrenomedullin without attenuating responses to ADP. Responses to adrenomedullin were 19 +/- 4% and 35 +/- 6% before and 6 +/- 3% and 19 +/- 5% after glibenclamide, respectively (P < .05). Iberiotoxin (10(-7) mol/L), an inhibitor of calcium-dependent K+ channels, also significantly attenuated responses to adrenomedullin and did not inhibit vasodilatation to papaverine. Responses to adrenomedullin were 16 +/- 2% and 55 +/- 8% before and 12 +/- 4% and 26 +/- 3% after iberiotoxin, respectively (P < .01 for 10(-6) mol/L adrenomedullin). CONCLUSIONS: Adrenomedullin produces substantial dilatation of cerebral arterioles in vivo, and the response is mediated in large part by activation of CGRP1 receptors. Cerebral vasodilatation to adrenomedullin appears to be dependent on activation of K+ channels.     

Amebiasis--a differential diagnosis from inflammatory bowel disease

Entamoeba histolytica is a very uncommon etiology of travelers diarrhoea, but may be an important differential diagnosis to inflammatory bowel disease. A misdiagnosis of amoebic colitis as inflammatory bowel disease followed by inadvertent treatment with corticosteroids may be fatal. Current techniques for the diagnosis of amoebiasis include stool studies, endoscopic biopsy and serology. Demonstration of haematophagous trophozoites in feces or in tissue biopsy is the definitive method for diagnosis. Unfortunately both methods have many drawbacks. If the specimens are negative, serology can support the diagnosis especially in a non-endemic area where a positive test is highly predictive of current disease.     

Renal cellular transport, metabolism, and cytotoxicity of S-(6-purinyl)glutathione, a prodrug of 6-mercaptopurine, and analogues

Plasmids currently used for nonviral gene transfer have the disadvantage of carrying a bacterial origin of replication and an antibiotic resistance gene. There is, therefore, a risk of uncontrolled dissemination of the therapeutic gene and the antibiotic resistance gene. Minicircles are new DNA delivery vehicles which do not have such elements and are consequently safer as they exhibit a high level of biological containment. They are obtained in E. coli by att site-specific recombination mediated by the phage lambda integrase. The desired eukaryotic expression cassette, bounded by the lambda attP and attB sites was cloned on a recombinant plasmid. The expression cassette was excised in vivo after thermoinduction of the integrase gene leading to the formation of two supercoiled molecules the minicircle and the starting plasmid lacking the expression cassette. In various cell lines, purified minicircles exhibited a two- to 10-fold higher luciferase reporter gene activity than the unrecombined plasmid. This could be due to either the removal of unnecessary plasmid sequences, which could affect gene expression or the smaller size of mini-circle which may confer better extracellular and intracellular bioavailability and result in improved gene delivery properties.     

Complete reversal of ischemic wall motion abnormalities by combined use of gene therapy with transmyocardial laser revascularization

1. The effects of the various doses of NG-nitro-L-arginine methyl ester (L-NAME, 10 and 30 mg/kg) on some cardiovascular and biochemical parameters during the early posthemorrhagic period were studied in anesthetized rabbits subjected to hemorrhagic hypovolemia. 2. Hemorrhagic shock was produced by intermittent bleeding of 40% of the estimated blood volume for 15 min. Blood samples were taken before and after bleeding (0, 15 and 60 min). Simultaneously, the mean arterial pressure (MAP) and the heart rate (HR) were measured. Hemorrhaged rabbits were treated by L-NAME10 or L-NAME30 (10 or 30 mg/kg, i.v. bolus injection, respectively) or the corresponding volumes of saline (0.6 ml, i.v. bolus) immediately after the end of bleeding. 3. The observed cardiovascular parameters (MAP, HR) were significantly reduced after the end of bleeding in all rabbits. 4. The rise of the MAP was significantly more pronounced 30 min after the injection of L-NAME30 in comparison with the corresponding values in the saline (S) group. In contrast, L-NAME10 produced only a small, insignificant increase in the MAP in hemorrhaged rabbits. 5. The L-NAME30-induced rise of the MAP was accompanied by a severe bradycardia, hyperkalemia and an aggravated metabolic acidosis, more severe than the corresponding disturbance of the acid-base status in the S group. The changes in the acid-base parameters were observed both in arterial (pH, excess base) and in venous blood (pH) of hemorrhaged rabbits. 6. In conclusion, the i.v. bolus injection of L-NAME30 (immediately after the end of bleeding) produced a significant increase in the MAP during the first hour after the injury, but the presumable inhibition of the endothelial constitutive nitric oxide synthase during the early posthemorrhagic period resulted in severe cardiovascular and metabolic disturbances.     

Identification of a novel human RAD51 homolog, RAD51B

OBJECTIVE: To assess the relation between morbidity from acute diarrhea and the form of day care. STUDY DESIGN: The design was a retrospective cohort study. The setting was the city of Espoo, an urban-suburban municipality in southern Finland with a population of 170,000. The study population comprised 2568 randomly selected children aged 1 to 7 years. The main outcome measure was the occurrence of diarrhea. RESULTS: Children in day-care centers (DCCs) had an increased risk for acute diarrhea compared with children in home care. In the whole group of children in DCCs, the relative risk was 1.20 (95% confidence interval [CI], 1.08 to 1.34). The risk was greatest in 1- and 2-year-old children, for whom the estimated relative risks were 1.76 (95% CI, 1.28 to 2.43) and 1.56 (95% CI, 1.16 to 2.09), respectively. The proportion of diarrhea episodes attributable to DCC care in 1-year-old children was 49% (95% CI, 18% to 91%), in 2-year-old children 37% (95% CI, 11% to 73%), and in the whole group 17% (95% CI, 7% to 29%). The infection risk did not differ between children in home and family care. CONCLUSIONS: The results provide quantitative evidence that the care in DCCs is a major determinant of acute diarrhea in children, whereas family day care does not increase the infection risk.