Randomised trial of two pharmacological methods of bowel preparation for day case colonoscopy.
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AIMS: To undertake a prospective, single blind, randomised trial comparing the efficacy and tolerance of two outpatient colonoscopy bowel preparation regimens. METHODS: Patients aged between 18 months and 16 years being admitted for day case colonoscopy were allocated randomly to receive either Picolax (an oral, sugar free powder containing sodium picosulphate 10 mg/sachet with magnesium citrate) and clear fluids or bisacodyl tablets with an unrestricted diet and a phosphate enema just before colonoscopy. Patient compliance, bowel frequency, and associated symptoms were recorded, and the adequacy of the bowel preparation was assessed in a blinded manner. RESULTS: 63 of 66 patients completed the trial. Mean age, mean weight, extent of colonoscopy, and distribution of underlying pathology were similar in both groups. Bowel preparation was good or excellent in all of the patients in the Picolax group (n = 32) compared with 22 patients in the bisacodyl/phosphate enema group (n = 31). The latter group experienced more abdominal discomfort during bowel preparation but three of the Picolax group vomited and the lack of solid food distressed some children. CONCLUSIONS: All bowel preparation methods have limitations and unpleasant side effects but the use of Picolax and clear fluids proved superior to bisacodyl tablets and a phosphate enema in children undergoing day case colonoscopy. (+info)
Mitochondrial potassium channel opener diazoxide preserves neuronal-vascular function after cerebral ischemia in newborn pigs.
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BACKGROUND AND PURPOSE: N-Methyl-D-aspartate (NMDA) elicits neuronally mediated cerebral arteriolar vasodilation that is reduced by ischemia/reperfusion (I/R). This sequence has been preserved by pretreatment with the ATP-sensitive potassium (K(ATP)) channel opener aprikalim, although the mechanism was unclear. In the heart, mitochondrial K(ATP) channels (mitoK(ATP)) are involved in the ischemic preconditioning-like effect of K(+) channel openers. We determined whether the selective mitoK(ATP) channel opener diazoxide preserves the vascular dilation to NMDA after I/R. METHODS: Pial arteriolar diameters were determined with the use of closed cranial window/intravital microscopy in anesthetized piglets. Vascular responses to NMDA were assessed before and 1 hour after 10 minutes of global cerebral ischemia induced by raising intracranial pressure. Subgroups received 1 of the following pretreatments before I/R: vehicle; 1 to 10 micromol/L diazoxide; and coapplication of 100 micromol/L 5-hydroxydecanoic acid (5-HD), a K(ATP) antagonist with diazoxide. RESULTS: NMDA-induced dose-dependent pial arteriolar dilation was not affected by diazoxide treatment only but was severely attenuated by I/R. In contrast, diazoxide dose-dependently preserved the NMDA vascular response after I/R; at 10 micromol/L, diazoxide arteriolar responses were unaltered by I/R. The effect of diazoxide was antagonized by coapplication of 5-HD with diazoxide. Percent preservation of 100 micromol/L NMDA-induced vasodilation after I/R was 53+/-19% (mean+/-SEM, n=8) in vehicle-treated controls versus 55+/-10%, 85+/-5%, and 99+/-15% in animals pretreated with 1, 5, and 10 micromol/L diazoxide (n=8, n=8, and n=12, respectively) and 60+/-15% in the group treated with 5-HD+diazoxide (n=5). CONCLUSIONS: The mitoK(ATP) channel opener diazoxide in vivo preserves neuronal function after I/R, shown by pial arteriolar responses to NMDA, in a dose-dependent manner. Thus, activation of mitoK(ATP) channels may play a role in mediating the protective effect of other K(+) channel openers. (+info)
Iron primes hepatic macrophages for NF-kappaB activation in alcoholic liver injury.
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NF-kappaB activation induced by lipopolysaccharide (LPS) in cultured hepatic macrophages (HM) may be abrogated by pretreatment of cells with a lipophilic iron chelator, 1,2-dimethyl-3-hydroxypyrid-4-one (L1, deferiprone), suggesting a role for iron in this molecular event [M. Lin, M., R. A. Rippe, O. Niemela, G. Brittenham, and H. Tsukamoto, Am. J. Physiol. 272 (Gastrointest. Liver Physiol. 35): G1355-G1364, 1997]. To ascertain the relevance in vivo of this hypothesis, HM from an experimental model of alcoholic liver injury were examined for the relationship between nuclear factor (NF)-kappaB activation and iron storage. HM showed a significant increase in nonheme iron concentration (+70%), accompanied by enhanced generation of electron paramagnetic resonance-detected radicals (+200%), NF-kappaB activation (+100%), and tumor necrosis factor-alpha (+150%) and macrophage inflammatory protein-1 (+280%) mRNA induction. Treatment of the cells ex vivo with L1 normalized all these parameters. HM content of ferritin protein, ferritin L chain mRNA, and hemeoxygenase-1 mRNA and splenic content of nonheme iron were increased, suggesting enhanced heme turnover as a cause of the increased iron storage and NF-kappaB activation. To test this possibility, increased iron content in HM was reproduced in vitro by phagocytosis of heat-treated red blood cells. Treatment caused a 40% increase in nonheme iron concentration and accentuated LPS-induced NF-kappaB activation twofold. Both effects could be abolished by pretreatment of cells with zinc protoporphyrin, a hemeoxygenase inhibitor. To extend this observation, animals were splenectomized before 9-wk alcohol feeding. Splenectomy resulted in further increments in HM nonheme iron storage (+60%) and NF-kappaB activation (+90%) and mononuclear cell infiltration (+450%), particularly around the iron-loaded HM in alcohol-fed animals. These results support the pivotal role of heme-derived iron in priming HM for NF-kappaB activation and expression of proinflammatory genes in alcoholic liver injury. (+info)
The relationship between metal-metal distance of two metal ions chelated complex and RNA cleavage activity.
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We prepared a series of ligands possessing two binding sites for metal coordination: in each ligand molecule, two binding sites with the same functionality (2,2'-dipicolylamino group) were placed at the of various methyl arenes. Thus, the distances between the metal binding sites were different from ligand to ligand. We examined the rate of the hydrolysis of RNA dimer catalyzed by La3+ ion binuclear complexes of the ligands. The catalytic activity of the binuclear complexes increased as the distance between the metal binding sites was decreased. (+info)
Single blind, randomised trial of efficacy and acceptability of oral picolax versus self administered phosphate enema in bowel preparation for flexible sigmoidoscopy screening.
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OBJECTIVE: To compare the acceptability and efficacy of two methods of self administered bowel preparation for flexible sigmoidoscopy screening: a single phosphate enema and a single sachet of Picolax. DESIGN: Single blind, randomised trial. SETTING: Endoscopy units of two general hospitals. PARTICIPANTS: 1442 men and women aged 55-64 years who had agreed to be screened by flexible sigmoidoscopy. MAIN OUTCOME MESURESs: Attendance rates, compliance with allocated preparations, adverse effects, quality of bowel preparation, procedure time, and yield of neoplasia. RESULTS: Compliance with the enema was higher than with the Picolax (608 (84%) v 566 (79%); difference 6%, 95% confidence interval 2% to 10%). Almost half of those who refused Picolax used an enema at home. Wind, incontinence, and sleep disturbance were more frequent in the Picolax group than the enema group; bottom soreness was more frequent in the enema group. Around 30% (187) found the diet restriction required by Picolax difficult; 78% (471) found the enema easy to administer. The quality of preparation was better with the enema; the proportion of procedures complete to the descending colon was greater and the mean duration of the procedure was shorter. There was no significant difference in polyp detection rates. CONCLUSION: A single phosphate enema self administered around one hour before leaving home is a more acceptable and effective method of preparing the distal bowel for flexible sigmoidoscopy than Picolax. (+info)
Gordonia nitida sp. nov., a bacterium that degrades 3-ethylpyridine and 3-methylpyridine.
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A bacterial strain, LE31T, which is capable of degrading 3-ethylpyridine and 3-methylpyridine, was isolated from an industrial wastewater and was taxonomically studied by using a polyphasic approach. Strain LE31T was identified as a member of the genus Gordonia on the basis of chemotaxonomic characteristics and phylogenetic inference-based 16S rDNA sequence. The cell wall contained meso-diaminopimelic acid, arabinose and galactose (wall chemotype IV). The predominant menaquinone was MK-9(H2). The mycolic acids contained 47-55 carbon atoms. The major fatty acids were C16:0, C18:1 omega9c, 10-methyl-C18:0 (TBSA). The G+C content of DNA was 67 mol%. The 16S rDNA sequence of strain LE31T was most similar to that of the type strain of Gordonia rubropertincta. The differences in some phenotypic characteristics and the genetic distinctiveness distinguish strain LE31T from the Gordonia species described previously. Therefore it is proposed that strain LE31T should be placed in the genus Gordonia as a new species. The name Gordonia nitida is proposed for strain LE31T. The type strain of the new species is strain LE31T (= KCTC 0605BPT = KCCM 80004T). (+info)
The inhibitory potency and selectivity of arginine substrate site nitric-oxide synthase inhibitors is solely determined by their affinity toward the different isoenzymes.
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We have investigated various nitric oxide (NO) synthase inhibitors for their affinity and selectivity toward the three human isoenzymes in radioligand binding experiments. Therefore, we developed the new radioligand [(3)H]2-amino-4-picoline to measure binding of these compounds to the three human NO synthase (NOS) isoenzymes. Aminopicoline is a potent and nonselective inhibitor of all three isoforms. [(3)H]2-amino-4-picoline bound saturably and with high affinity to human NOSs. Affinity constants (K(D) values) of 59, 111, and 136 nM were obtained for the inducible, neuronal, and endothelial NOS isoforms (iNOS, nNOS, eNOS). Binding of [(3)H]2-amino-4-picoline was competitive with the substrate arginine. From all the inhibitors tested, AMT (2-amino-5, 6-dihydro-6-methyl-4H-1,3-thiazine hydrochloride) showed the highest affinity and no selectivity. L-NIL [L-N(6)-(1-Iminoethyl)lysine hydrochloride] and aminoguanidine were moderately iNOS-selective while L-NA (N(G)-nitro-L-arginine) and L-NAME (N(G)-nitro-L-arginine methyl ester hydrochloride) showed selectivity toward the constitutive isoforms. High iNOS versus eNOS selectivity was found for 1400W, whereas several isothiourea derivatives and 1400W displayed moderate n- versus eNOS selectivity. To relate the affinity of these compounds to their inhibitory potency, we measured the inhibitory potency under almost identical conditions using a new microtiter plate assay. The inhibitory potency of selective and nonselective NOS inhibitors was almost exactly mirrored by their affinity toward the different isoenzymes. Highly significant correlations were obtained between the potency of enzyme inhibition and the inhibition of [(3)H]2-amino-4-picoline binding for all three isoenzymes. These data show that the potency and selectivity of NOS inhibitors are solely determined by their affinity toward the different isoforms. Furthermore, these data identify the new radioligand [(3)H]2-amino-4-picoline as a very useful radiolabel for the investigation of the substrate binding site of all three isoforms. (+info)
Role of inwardly rectifying K(+) channels in K(+)-induced cerebral vasodilatation in vivo.
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We tested whether activation of inwardly rectifying K(+) (Kir) channels, Na(+)-K(+)-ATPase, or nitric oxide synthase (NOS) play a role in K(+)-induced dilatation of the rat basilar artery in vivo. When cerebrospinal fluid [K(+)] was elevated from 3 to 5, 10, 15, 20, and 30 mM, a reproducible concentration-dependent vasodilator response was elicited (change in diameter = 9 +/- 1, 27 +/- 4, 35 +/- 4, 43 +/- 12, and 47 +/- 16%, respectively). Responses to K(+) were inhibited by approximately 50% by the Kir channel inhibitor BaCl(2) (30 and 100 microM). In contrast, neither ouabain (1-100 microM, a Na(+)-K(+)-ATPase inhibitor) nor N(G)-nitro-L-arginine (30 microM, a NOS inhibitor) had any effect on K(+)-induced vasodilatation. These concentrations of K(+) also hyperpolarized smooth muscle in isolated segments of basilar artery, and these hyperpolarizations were virtually abolished by 30 microM BaCl(2). RT-PCR experiments confirmed the presence of mRNA for Kir2.1 in the basilar artery. Thus K(+)-induced dilatation of the basilar artery in vivo appears to partly involve hyperpolarization mediated by Kir channel activity and possibly another mechanism that does not involve hyperpolarization, activation of Na(+)-K(+)-ATPase, or NOS. (+info)