Search PubMed⌕ Search

Biomedical subjects

S Kuroki

Publications and source records attributed to S Kuroki.

At least 163 records · Page 9Linked to original sources
PubMed1989

Deoxycholate 7 alpha-hydroxylase in the hamster: substrate specificity and effect of phenobarbital.

In a recent publication, we reported that deoxycholic acid is 7 alpha-hydroxylated to yield glycocholate or taurocholate in vivo in the hamster (1987. Kuroki et al. Hepatology. 7: 229-234). In order to explore the possibility that amidation of free deoxycholic acid precedes the 7 alpha-hydroxylation, we assayed 7 alpha-hydroxylase activities of free and conjugated deoxycholates in vitro. 7 alpha-Hydroxylase activities of glycodeoxycholate and taurodeoxycholate were 720 +/- 132 and 640 +/- 160 pmol/mg.min-1, respectively. Activity of 7 alpha-hydroxylation of free deoxycholate was very low (60 +/- 20 pmol/mg.min-1). After treatment with phenobarbital in a dose of 100 mg/kg per day for 6 days, 7 alpha-hydroxylase activities of conjugated deoxycholates were decreased significantly (40%, P less than 0.01, n = 8), whereas that of free deoxycholate was not significantly changed. In the rat, 7 alpha-hydroxylase activities of conjugated deoxycholates were induced significantly (45% increase, P less than 0.05, n = 5) by phenobarbital treatment in sharp contrast to the hamster. There were significant correlations between the 7 alpha-hydroxylase activity of taurodeoxycholate and that of glycodeoxycholate both in the hamster and in the rat (hamsters: n = 16, r = 0.98, P less than 0.01; rats: n = 10, r = 0.82, P less than 0.01). These studies suggested that deoxycholic acid is 7 alpha-hydroxylated after amidation with glycine or taurine in vivo and that the same enzyme may well catalyze the 7 alpha-hydroxylation of glycodeoxycholate and taurodeoxycholate in the hamster.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

[Transferability of cefodizime to cerebrospinal fluid of rabbits with meningitis caused by Staphylococcus aureus].

The transferability of cefodizime (THR-221, CDZM) to cerebrospinal fluid (CSF) was studied employing rabbits with experimental meningitis caused by Staphylococcus aureus. The mean blood concentration was 195 +/- 18.3 micrograms/ml using phosphate buffer solution (PBS) standard and 474 +/- 22.0 micrograms/ml using rabbit serum standard, respectively, at 15 minutes after intravenous administration of the drug at a dose level of 100 mg/kg. The mean concentration in CSF vs. PBS standard was maximum at 60 minutes after administration, and the mean maximum concentration was 8.74 +/- 2.16 micrograms/ml. Pharmacokinetic parameters calculated from those values were as follows, respectively, for PBS standard and rabbit serum standard; Cmax (CSF/serum): 4.48% and 1.84%. AUC (CSF/serum): 6.15% and 2.02% between 15 and 60 minutes, 10.6% and 3.00% between 15 and 120 minutes and 13.4% and 3.48% between 15 and 180 minutes. T 1/2 for CDZM in CSF: 141 minutes in both cases. T 1/2 (CSF/serum): 3.27 and 2.11. Concentrations in CSF determined using an high performance liquid chromatography method in another rabbits were similar to those determined using the bioassay vs. rabbit serum standard. The bioassayed concentration of this drug (AUC (CSF/serum] vs. PBS standard ranked 9th among 23 other beta-lactam antibiotics tested. That is, the drug distributed favorably as compared to other antibiotics, and it may be worthwhile of running clinical trials on this drug in meningitis when antimicrobial potential against main pathogens of meningitis are considered.

Animals↗
PubMed1989

[Clinical experience with cefodizime on pediatric infections].

Cefodizime (THR-221, CDZM), a newly developed injectable cephem antibiotic, was injected intravenously to 13 cases of pediatric infections. Patients received the drug at a dose level of approximately 20 mg/kg x 3 times daily. The results obtained are summarized as follows. 1. Clinical efficacy was excellent in 4 patients, good in 6 and poor in 0 for 10 cases (2 phlegmon, 1 periproctal abscess, 5 pneumonia and 2 bronchitis) except 3 Mycoplasma pneumonia. 2. Three strains of pathogens were followed for their changes (Streptococcus pyogenes in 1 phlegmon, Klebsiella pneumoniae in periproctal abscess and Haemophilus influenzae in 1 bronchitis) and they were found to have been eliminated. 3. No adverse reactions occurred. Abnormal changes in laboratory test data found were 2 cases of eosinophilia, 1 cash each of increased GOT and GPT, and thrombocytosis, but none of them was severe.

Adolescent↗
PubMed1989

[A clinical study on cefteram pivoxil granule in the field of pediatrics].

The clinical effectiveness of cefteram pivoxil (CFTM-PI) granule, a new oral cephalosporin, was studied in pediatric patients. The results are summarized as follows. 1. CFTM-PI was given orally to 17 children in daily doses of 9.5 to 31.8 mg/kg in 3 to 4 divided portions for 2 to 10 days. Clinical evaluations were made on 14 patients. Clinical effects of CFTM-PI were excellent in 4, good in 5 of 9 patients with tonsillitis or pharyngitis, excellent in all cases of 2 patients with pneumonia, 1 patient with scarlet fever and 1 patient with pyelonephritis, and fair in 1 patient with purulent cervical lymphadenitis. Overall clinical effects were excellent in 8, good in 5, and fair in 1 with an efficacy rate of 92.9%. 2. No side effects were observed in any of the 17 patients. Hematological tests showed a slight elevation of blood platelet counts in 1 patient. 3. The taste and odor of CFTM-PI granule were well accepted by the children. 4. CFTM-PI is a useful oral antibiotic for the treatment of bacterial infections in pediatrics.

Bacterial Infections↗
PubMed1988

Dissolution of cholesterol gallstones by bile acids in the prairie dog.

The effect of chenodeoxycholic acid, ursodeoxycholic acid and hyodeoxycholic acid on gallstone dissolution was studied in the prairie dog. Cholesterol gallstones were found in all animals after feeding a semipurified diet plus 1.2% cholesterol for six wk. Gallstone regression was examined by feeding a chow diet containing the bile acids (chenodeoxycholic acid, ursodeoxycholic acid or hyodeoxycholic acid) alone (30 mg/kg/day) or in combination (chenodeoxycholic acid plus ursodeoxycholic acid) for an additional six wk. Chenodeoxycholic acid was effective in dissolving established cholesterol gallstones (two out of 16 animals still had stones) and cholesterol crystals (six out of 16 animals had crystals); the hydrophilic bile acids, ursodeoxycholic acid and hyodeoxycholic acid, were ineffective in the six-wk regression study. The lithogenic indices averaged 1.09 at the end of the induction period; all biles became unsaturated with respect to cholesterol after the six-wk regression period (group 1, 0.82; group 2, 0.66; group 3, 0.81; group 4, 0.84; group 5, 0.66). Cholesterol levels in liver, plasma and bile were elevated after the six-wk induction phase (4.59 mg/g, 610 mg/dl and 0.36 mg/ml, respectively) but returned to near normal levels after the six-wk regression period. Biliary bile acids contained increased levels of the dietary bile acid administered to each group. This experiment shows that relatively hydrophobic bile acids may be more effective than hydrophilic bile acids for gallstone dissolution during the period studied.

Animals↗
PubMed1988

Effect of 7-methylated bile acids and bile alcohols on cholesterol metabolism in hamsters.

The effect of 7-methyl substituted bile acid and bile alcohol analogues on cholesterol metabolism was studied in the hamster. Animals were fed chow plus 0.1% cholesterol supplemented with 0.1% of one of the following steroids: chenodeoxycholic acid, 7-methyl-chenodeoxycholic acid, 7 beta-methyl-24-nor-5 beta-cholestane-3 alpha, 7 alpha, 25-triol, cholic acid, 7-methyl-cholic acid, or 7 beta-methyl-24-nor-5 beta-cholestane-3 alpha, 7 alpha, 12 alpha,25-tetrol. Cholesterol absorption was determined from fecal analysis after feeding of radiolabeled cholesterol and beta-sitosterol. Of the six compounds studied, chenodeoxycholic acid and 7-methyl-chenodeoxycholic acid decreased intestinal cholesterol absorption (17% and 31% decrease, respectively). Only 7-methyl-chenodeoxycholic acid decreased serum cholesterol concentration (29% decrease), but there were no analogous changes of liver and biliary cholesterol concentration and cholesterol saturation of bile. Total fecal neutral sterol excretion was increased in the groups fed chenodeoxycholic acid and 7-methyl-chenodeoxycholic acid. In addition, the production of coprostanol was increased in both groups. These data suggest that 7-methyl-chenodeoxycholic acid resembles chenodeoxycholic acid in its effect on cholesterol metabolism and may be a potential candidate for further studies of its gallstone-dissolving properties.

Animals↗
PubMed1988

[Clinical studies of rokitamycin dry syrup in the field of pediatrics].

We studied the absorption and excretion as well as the clinical effect of rokitamycin (RKM, TMS-19-Q) dry syrup. The results we found are summarized as follows: 1. When 3 pediatric patients were medicated orally with a single dose of 10 mg/kg of the drug, its peak concentrations of 0.75 and 0.51 microgram/ml appeared in the blood in 30 minutes after administration in 2 patients, and of 0.21 microgram/ml in 1 hour in the other patient. At 4 hours after administration, its concentration in the blood was 0.07-0.08 microgram/ml in all of the patient, and at 6 hours, it was undetectable. T1/2 values were 1.05-2.08 hours. First 6-hour urinary recovery rates of the drug in the first 2 patients were 1.52 and 1.11%, respectively. 2. Twenty-four patients with 25 diseases were medicated with 7.14-12.5 mg/kg of the drug 3-4 times daily for 4-10 days. The patients consisted of 12 with tonsillitis, 7 with bronchitis, 3 with colitis, one each with Haemophilus influenzae pneumonia, mycoplasmal pneumonia, and pertussis. Clinical responses to the treatment were excellent in 7, good in 13, and poor in 5, with an efficacy rate of 80.0%. Bacteriologically, of 17 isolates whose changes were followed, 8 were eradicated, 1 decreased, and 8 remained unchanged, with an eradication rate of 47.1%. 3. No adverse reactions to the drug were observed in any of these patients, while abnormal laboratory test values observed were slight eosinophilia and also slight elevations of S-GOT and S-GPT in one of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1988

[Clinical evaluation of ceftizoxime in neonates and premature infants].

Ceftizoxime (CZX) was evaluated for absorption and excretion as well as for therapeutic effectiveness in neonates and premature infants. The following results were obtained. 1. Serum CZX concentrations were determined in 8 neonates or premature infants who were not more than 6 days old. Serum concentrations of the drug were examined in 6 neonates and/or premature infants after intravenous administration of about 20 mg/kg body weight. Average concentration at 1/2, 2, 4 and 6 hours after administration were 52.3, 36.4, 26.7 and 16.7 micrograms/ml, respectively. Serum concentrations in the other 2 infants who were given 29.7 and 25.1 mg/kg, were as high as 71 and 94 micrograms/ml at 1/2 hour and 22.1 and 39 micrograms/ml at 6 hours, respectively. Serum half-lives in 5 of the 6 mature neonates ranged from 2.36 to 3.34 hours, with averaged 2.75 hours, but was exceptionally long, 7.92 hours, in the other one. Half-lives in the 2 premature infants were 4.14 and 4.90 hours. 2. The therapeutic effectiveness on bacterial infection was evaluated for 10 newborn infants. Intravenous doses of 16.9 to 24.6 mg/kg were given in b.i.d. or t.i.d. regimen to 4 cases with pneumonia and 2 with septicemia, urinary tract infection and fetal infection each. To 1 infant with septicemia complicated with cephalohematoma, higher doses ranged from 21.8 to 49.8 mg/kg were given t.i.d. or q.i.d. Therapeutic efficacies were assessed as "Excellent" in 3, "Good" in 6, and "Poor" in 1, with an efficacy rate of 90.0%. Eradication of bacteria was complete in 2 infants each with Escherichia coli-induced septicemia or urinary tract infection. 3. For prophylactic use, the drug was given to 8 newborn infants in intravenous doses of 17.5 to 29.1 mg/kg b.i.d. or t.i.d. and no infection occurred in 7 cases. 4. No adverse reactions were obtained. Slight and transient increases in platelet count, GOT and GPT in 1 case and eosinophilia in another were observed. 5. These results suggested that CZX in an intravenous dose of 20 mg/kg b.i.d. or t.i.d. regimen in newborn infants up to 7 days of age would be effective and safe for the treatment of neonatal bacterial infections.

Absorption↗
PubMed1988

[Morphometrical study on prognosis of stage I pulmonary adenocarcinoma].

The prognostic significance of morphometry in stage I pulmonary adenocarcinoma had been examined in Papanicolaou-stained bronchial brushings, using an image analyzer. The data of long-term survivors (LTS), alive for more than 5 years, and short-term survivors (STS), who had died within 5 years, were compared. LTS were found to have a smaller nuclear area, a shorter nuclear perimeter, and a smaller nucleolar area than those of the STS. The nuclear size is considered important in any histological subtypes. The variation index of the nuclear area, the nuclear circularity, and the number of nucleoli did not differ between the two groups. These results would seem to be useful in determining the prognosis and the indication type of adjuvant therapy to be used in surgical operations.

Adenocarcinoma↗
PubMed1988

[Clinical experience with sultamicillin fine granules in pediatric field].

Sultamicillin fine granules were used orally in 18 pediatric patients with infections in doses ranging 7.3-10.0 mg/kg t.i.d. or q.i.d. The following is a summary of the results: 1. Clinical efficacies in 16 cases with tonsillitis were excellent in 13 cases, good in 2 cases and fair in 1 case. Efficacy in 1 case of bronchitis and 1 case of pneumonia were good. The overall efficacy rate in the 18 cases was 94.4%. 2. Four out of 5 strains of Staphylococcus aureus were eradicated but 1 strain persisted. Three out of 7 strains of Haemophilus influenzae were rated as eradicated, 1 strain as decreased and 3 strains as persisted. Two strains of Streptococcus pyogenes and 3 strains of Haemophilus parainfluenzae were eradicated. The bacteriological efficacy rate for the 17 strains was 70.6%. Four strains out of the 17 were found to produce beta-lactamase and 3 strains were suspected, to produce the enzyme, but of these 7 strains, 5 strains were eradicated. 3. Diarrhea and loose stool were observed as side effects in each of 2 cases. It appeared that diarrhea was related to this drug. A slight elevation of GOT was observed in 1 case in laboratory tests. 4. This drug appears to be easy for children to take in terms of taste and smell.

Age Factors↗
PubMed1988

[Cerebral blood flow and oxygen metabolism in patients with Parkinson's disease].

The distribution of cerebral blood flow and metabolism is related to neuronal activity. Cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), and oxygen extraction fraction (OEF) in ten patients with Parkinson's disease and five age-matched normal control subjects were measured with positron emission tomography (PET) using 15O2, C15O2 steady state inhalational technique to investigate functional changes of the cortex and the basal ganglia in Parkinson's disease. All patients had no history of cerebrovascular disease and CT scan showed no abnormal findings except for moderate cerebral atrophy in only one patient. When the level of clinical disability was related on the scale of Hoehn and Yahr, one patient was stage I, four were stage II, four were stage III, and one was stage IV. Psychic symptoms which include hallucination, depression, and dementia were recognized in four patients. One of these four patients was mildly demented. Four patients were newly diagnosed and had never been treated with antiparkinsonian medication before. Before the patients had their PET study their antiparkinsonian medication was discontinued for more than three days. But in two patients PET study was performed without discontinuity of antiparkinsonian medication. The values for regional CBF and regional CMRO2 were lower in the patients than in the normal control subjects, especially in the frontal cortex there was a significant decrease of CBF and CMRO2. There was no discrepancy between CBF and CMRO2 both in the patients and the normal control. CBF and CMRO2 in the cortex and the basal ganglia were not correlated with the severity of tremor, bradykinesia, and rigidity.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

Bile salts of the West Indian manatee, Trichechus manatus latirostris: novel bile alcohol sulfates and absence of bile acids.

The bile salts present in gallbladder bile of the West Indian manatee, Trichechus manatus latirostris, an herbivorous marine mammal of the tropical and subtropical margins of the Atlantic Ocean, were found to consist of a mixture of bile alcohol sulfates. Bile acids, previously believed to be present in all mammals, were not detected. Using chromatography, mass spectrometry, and 1H- and 13C-nuclear magnetic resonance spectroscopy, the major bile alcohol was identified as 5 beta-cholestane-3 alpha,6 beta,7 alpha-25,26-pentol; that is, it had the nuclear structure of alpha-muricholic acid and the side chain structure of bufol. This compound has not been described previously and the trivial name "alpha-trichechol" is proposed. The second most abundant compound was 5 beta-cholestane-3 alpha,7 alpha,25,26-tetrol. Other bile alcohols were tentatively identified as 5 beta-cholestane-3 alpha,6 beta,7 beta,25,26-pentol (named beta-trichechol), 3 alpha,6 alpha,7 beta, 25-26-pentol (named omega-trichechol) and 5 beta-cholestane-3 alpha,6 beta,7 alpha,26-tetrol. The 1H and 13C NMR spectra of the four 6,7 epimers of 3,6,7 trihydroxy bile acids are described and discussed. All bile alcohols were present as ester sulfates, the sulfate group being tentatively assigned to the 26-hydroxy group. 12-Hydroxy compounds were not detected. The manatee is the first mammal found to lack bile acids, presumably because it lacks the enzymes required for oxidation of the 26-hydroxy group to a carboxylic acid. Trichechols, like other bile salts, are water-soluble end products of cholesterol metabolism; whether they also function as biological surfactants in promoting biliary cholesterol secretion or lipid digestion is unknown.

Animals↗
PubMed1987

An animal model of pigment cholelithiasis.

Pigment stones of high calcium content were induced in male hamsters of the Harlan Sprague-Dawley strain fed a nutritionally adequate semipurified diet for a period of 14 weeks. The diet contained moderate amounts of cholesterol (0.30 percent) and ethinyl estradiol (15 micrograms/day per animal). At sacrifice, the incidence of pigment stones was 50 percent. When stones were present, they were in the form of numerous black amorphous rods about 0.1 to 0.4 mm in length. Infrared analysis of the dried stones indicated the following composition: calcium phosphate 26.7 percent, calcium bilirubinate 12.8 percent, cholesterol 15.1 percent, and protein 45.4 percent. Pigment stones were associated with an elevated biliary total calcium level (probably induced by the dietary cholesterol) and a paradoxic decrease in the biliary total bilirubin level. The lithogenic diet produced marked elevations in liver and plasma cholesterol levels and cholesterol saturation of bile, but no cholesterol crystals or stones were observed. The accumulation of elevated levels of cholesterol in the livers of the experimental animals produced mild to moderate hepatotoxicity. The precise mechanism of the dietary induction of pigment stones in this hamster model remains to be elucidated.

Animals↗
PubMed1987

Metabolism of the bile acid analogues 7 beta-methyl-cholic acid and 7 alpha-methyl-ursocholic acid.

The metabolism of two new bile acid analogues, 7 beta-methyl-cholate and 7 alpha-methyl-ursocholate, was compared with that of cholate in the hamster. After intraduodenal administration of 14C-labeled compounds into bile fistula hamsters, radioactivity was exclusively recovered in bile; the more hydrophobic bile acid was absorbed more rapidly. Hepatic extraction of intravenously infused compounds was efficient and administered analogues became major biliary bile acids. Amidation of cholate was essentially complete, whereas 39% of 7 beta-methyl-cholate and 65% of 7 alpha-methyl-ursocholate were secreted in unconjugated form. After intragastric administration of the compounds, radioactivity was quantitatively recovered in feces. Cholate was 7-dehydroxylated to deoxycholate, whereas 31% of 7 beta-methyl-cholate and 78% of 7 alpha-methyl-ursocholate were recovered unchanged. Fifty percent of 7 beta-methyl-cholate and 15% of 7 alpha-methyl-ursocholate were transformed into ketonic derivatives, without loss of the 7-hydroxyl group. It is concluded that the introduction of the 7-methyl group did not interfere with intestinal absorption, hepatic extraction, and biliary secretion but did affect enzymatic amidation and bacterial 7-dehydroxylation of the analogues.

Animals↗
PubMed1987

Congenital muscular dystrophy of non-Fukuyama type with characteristic CT images.

A 9-year-old Japanese boy with congenital muscular dystrophy (CMD) with normal intelligence was presented. He was extremely floppy and had joint contractures since birth. Motor milestones were delayed and he did not learn to walk alone. Intellectual development was normal and no convulsions were observed. On physical examination at 9 years old, he had diffuse muscle weakness and atrophy and flexion contractures of joints. Creatine kinase was normal and IQ was 95. Biopsied muscle showed myopathic changes consistent with muscular dystrophy. CT scans of the head revealed diffuse low density area in the white matter of the cerebrum. These findings suggest central nervous system involvement in CMD is not confined to Fukuyama-type CMD.

Biopsy↗
PubMed1987

Congenital myopathy with type II muscle fiber hypoplasia.

We examined a 14-month-old boy with severe muscular hypotonia and weakness. Loss of tendon reflexes were noted at age 2 months. Right-sided heart failure and dyspnea during sleep developed at age 4 months. Muscle biopsy revealed selective hypoplasia of type II fibers and normal type I fibers. Intercostal and diaphragmatic muscles showed similar changes at necropsy and probably accented the respiratory failure.

Humans↗