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Biomedical subjects

A Rane

Publications and source records attributed to A Rane.

At least 181 records · Page 10Linked to original sources
PubMed1985

Isolation of nuclear fractions from human fetal tissues. Ultrastructure and presence of epoxide hydrolase and aryl hydrocarbon hydroxylase.

The aryl hydrocarbon hydroxylase (AHH) and epoxide hydrolase (EH) activities with styrene oxide and benzo[a]pyrene-4,5-oxide as substrates were investigated and compared in the nuclear and microsomal fractions isolated from the human fetal liver, adrenals, kidneys and lungs. The purity of the fractions was estimated by electron microscopy and found to be around 85% for the nuclear and 90% for the microsomal fractions. All tissues catalyzed the hydration of the two epoxides at significant rates. The EH followed Michaelis-Menten kinetics in all fractions. The highest activities were seen in the liver and the adrenals. The nuclear/microsomal ratios of the EH activity was tissue dependent, being highest in the kidneys and lungs. AHH was measurable in the microsomes of all investigated tissues. As to the nuclear fraction it was detectable only in the adrenals and the liver. The nuclear/microsomal ratio of AHH was four times higher in the adrenals than in the liver. It is concluded that not only the microsomal but also the nuclear fraction of several human fetal tissues have the potential of catalyzing formation and elimination of epoxides.

Adrenal Glands↗
PubMed1985

Positron emission tomography in experimental perinatology.

Positron emission tomography (PET) is a new tracer technique by which short-lived radionuclides, such as 11C are used for labeling drugs, amino acids and other compounds. The concentration in the various organs is determined non-invasively after I.V. injection. Positrons, emitted by 11C attract an electron, and the two masses are annihilated by emitting photons. These can be registered by external detectors. Measurement of the radioactivity per volume of tissue as a function of time is accomplished by computerized processing of the data. The PET technique may be used for studies of the kinetics of the injected compound in different organs of the body. However, PET registers only the total radioactivity meaning that the measured 11C-radioactivity represents the sum of the parent compound and the radiolabelled metabolites. Chemical and radiochemical analyses in various body fluids may then help to interpret the PET images.

Animals↗
PubMed1985

A prospective controlled trial of metoprolol-hydralazine treatment in hypertension during pregnancy.

In an open, controlled trial, treatment with a combination of metoprolol and hydralazine was compared with non-pharmacological management of mild and moderate hypertension in pregnancy. One hundred and sixty-one women participated in the study. The drug-treated group showed significantly better blood pressure control than the group not given antihypertensives. Induction of labor before term, because of maternal or fetal complications, was somewhat more frequent in the control group. Nine women in the treatment group and 5 in the control group developed albuminuria. Three infants in the drug-treated group died perinatally, and one in the control group. The outcome for the newborns was similar in both groups concerning birth weight, head circumference and Apgar score and in the frequencies of respiratory distress, bradycardia and hypoglycemia. The better blood pressure control achieved with these drugs makes it possible to treat the patient at home and reduce the risk of emergency delivery, but treatment does not seem to be mandatory for a good outcome of the pregnancy in cases of mild and moderate hypertension during pregnancy.

Adult↗
PubMed1985

Natural (-)- and unnatural (+)-enantiomers of morphine: comparative metabolism and effect of morphine and phenobarbital treatment.

The comparative metabolism of the natural (-)- and the unnatural (+)-morphine was studied in liver microsomes from phenobarbital-treated, morphine-treated and control rats. (-)-Morphine was glucuronidated only at position 3 with the formation of (-)-morphine-3-glucuronide [(-)-M3G] at an average rate of 2.19 nmol X mg protein-1 X min-1. In contrast, (+)-morphine was conjugated preferentially at position 6. The rate of formation of (+)-morphine-6-glucuronide [(+)-M6G] was 3.1 times higher than that of (+)-M3G (0.92 and 0.30 nmol X mg protein-1 X min-1, respectively). Natural morphine was N-demethylated at an average rate of 0.42 nmol X mg protein-1 X min-1, and this rate of N-demethylation was about twice as high as that of (+)-morphine (0.17 nmol X mg protein-1 X min-1). Phenobarbital treatment led to a 3- to 4-fold increase in the formation rate of (-)-M3G and (+)-M6G whereas the glucuronidation of (+)-morphine at position 3 was increased only marginally. No change in the N-demethylation of either enantiomer was observed. In contrast, pretreatment with (-)-morphine decreased the N-demethylation of both enantiomers by about 80% without any effect on the glucuronidation. The increased ratio of the rate of (+)-M6G/(+)-M3G formation after phenobarbital treatment indicates that different isozymes may be involved in the two reactions. This study demonstrates that there is an inherent substrate stereoselectivity and site selectivity for morphine in the rat hepatic uridine 5'-diphosphate-glucuronyltransferase although not as critical as for the opiate receptors mediating analgesia.

Animals↗
PubMed1984

Quantitation of clonazepam and its 7-amino and 7-acetamido metabolites in plasma by high-performance liquid chromatography.

A high-performance liquid chromatographic method is reported for the determination of clonazepam and its metabolites 7-amino- and 7-acetamidoclonazepam. Extraction from buffered plasma is carried out at pH 9.5 with hexane-ethyl acetate (7:3) for clonazepam and with chloroform for the metabolites. Flunitrazepam, 7-aminodemethylflunitrazepam and 7-acetamidoflunitrazepam are used as the internal standards for clonazepam and its 7-amino and 7-acetamido metabolites, respectively. To prevent decomposition of 7-aminoclonazepam a high concentration of 7-aminomethylclonazepam is added to the plasma. Chromatography is carried out on a reversed-phase column with detection at 254 nm for clonazepam and 240 nm for the metabolites. Using the method it was possible to determine 5 ng/ml clonazepam, 7-aminoclonazepam and 7-acetamidoclonazepam in plasma with coefficients of variation of 9.5%, 5.9% and 8.9%, respectively. This method can be used to measure clonazepam in plasma from patients treated with other antiepileptics. It may also be utilized for in vitro studies on the metabolism of clonazepam in subcellular fractions from the liver.

Anticonvulsants↗
PubMed1984

Human fetal liver cultures: basal activities and inducibility of epoxide hydrolases and aryl hydrocarbon hydroxylase.

The environmental influence of various drugs on the epoxide hydrolase with styrene oxide (EHSO) or benzo(a)pyrene-4,5-oxide (EHBPox) as substrate and the aryl hydrocarbon hydroxylase (AHH) activity was studied in monolayer cultures of human fetal hepatocytes (HFH) obtained at legal abortions. Hepatocytes were isolated by trypsin treatment of liver fragments and primary HFH cultures were maintained in Eagle's minimum essential medium supplemented with 15% newborn calf serum. The HFH were plated on culture dishes and allowed to 'settle' for one day before adding various drugs (in 1 microliter dimethylsulfoxide/ml) or solvent only and assay 1-2 days later. The basal AHH activity [assayed with 3H-benzo(a)pyrene as substrate] varied between 2 and 8.4 pmoles/min/mg protein and the basal EHSO activity was 0.3-4.9 nmoles/min/mg protein (n = 6) after one or two days' culture. The corresponding activity of EHBPox was 0.23-1.48 nmoles/min/mg protein (n = 5). Exposure of cultures to 2 mM phenobarbital (Pb), 2.5-25.0 microM benzanthracene (BA), 0.1 mM trans-stilbene oxide (TSO), or 5 microM beta-naphtoflavone (beta NF) resulted in a 1.2-3.7-fold induction of EHSO. Induction of EHBPox was also observed with Pb, beta NF, BA and TSO as inducers. Pb gave a dose-dependent induction of both EH at 0.1, 1.0 and 2.0 mM. Our results demonstrate that EH and AHH activities in HFH cultures are inducible by classical in vivo inducers. Although difficult to prove, it is plausible that such induction takes place also in intrauterine life.

Aryl Hydrocarbon Hydroxylases↗
PubMed1984

Clonazepam serum protein binding during development.

Clonazepam protein binding was investigated in sera from five different umbilical cords, 45 children (aged 2 mo to 12 yr), and five adults (aged 27 to 40 yr). The unbound fraction (means +/- SE) of clonazepam was 17.3% +/- 0.7% in umbilical cord serum and 13.9% +/- 0.2% in adult serum (P less than 0.01). In children, the unbound fraction of clonazepam reached the adult values during the first year of life. The kinetics of clonazepam serum protein binding were studied in three umbilical cord serum and three adult serum specimens. The number of binding sites (n, reported as moles per gram protein) and the association constant (K, reported as M-1) were estimated from double reciprocal plots of 1/r against 1/D (r is the number of moles bound per gram plasma protein; D is the molar concentration of unbound drug). In umbilical cord sera, the mean values (+/- SE) of n and K were 8.4 +/- 0.6 X 10(-7) mol/gm and 8.3 +/- 0.9 X 10(4) M-1. In adult serum samples the corresponding values were 3.0 +/- 0.8 X 10(-7) mol/gm and 2.7 +/- 0.6 X 10(5) M-1, which indicated lower binding capacity but higher affinity for clonazepam of plasma proteins in adults than in children.

Adult↗
PubMed1984

Kinetics of morphine in cerebrospinal fluid after epidural administration.

Forty patients undergoing arthroscopy were given an epidural dose of 0.05 mg morphine-HCl in 0.1 ml saline/kg body weight to study the disposition of morphine in the cerebrospinal fluid (CSF). In each patient one to three CSF samples were collected (86 samples in total). A mean peak concentration of 13 890 nmol/l was achieved 75 min after morphine administration. The compiled data show an elimination half-life of 162 min (r = 0.98). Individual half-lives in seven patients with three samples ranged from 61-172 min. Large interindividual variations were found in CSF-concentrations of morphine, 9- and 8-fold at 3 and 8 h, respectively, after the dose. However, 16 h after administration no patient had a concentration less than 81 nmol/l. At 8 h after the dose, CSF concentrations of morphine were significantly higher (P less than 0.05) in a group of patients (n = 5) kept uptilted (80 degrees), as compared to those in the supine position (n = 5). Such a difference was not observed 3 h after the dose. The sampling procedure and age also seemed to influence CSF concentrations of morphine. There was no correlation between the dose given in mg and the CSF concentrations achieved. Strict standardization is thus mandatory when studying the disposition of opiates in CSF after epidural or intrathecal administration. Since our calculated half-lives of morphine in CSF were similar to those reported in plasma, the long-lasting effect is probably related to the high initial morphine concentrations in CSF.

Adult↗
PubMed1984

Nuclear epoxide hydrolase in the human fetal and adult liver.

The epoxide hydrolase activity with styrene oxide as substrate was investigated in the nuclear fraction of human fetal and adult liver specimens. All investigated liver fractions catalyzed the hydration of styrene oxide and the average epoxide hydrolase activities were 0.37 and 1.90 nmol/min/mg protein in fetal and adult specimens, respectively. The enzyme followed Michaelis-Menten kinetics in fetal nuclear fraction and biphasic kinetics in adult livers. The nuclear/microsomal enzyme activity ratios of epoxide hydrolase were 0.09 and 0.11 for fetal and adult livers, respectively.

Adult↗
PubMed1984

Subcellular distribution of styrene oxide in rat liver.

The subcellular distribution of (3H )-styrene-7,8-oxide was studied in the rat liver. The compound was added to liver homogenate to give a final concentration of 2 X 10(-5); 2 X 10(-4) and 2 X 10(-3) M. Subcellular fractions were obtained by differential centrifugation. Most of styrene oxide (59-88%) was associated with the cytosolic fraction. Less than 15 percent of the compound was retrieved in each of the nuclear, mitochondrial and microsomal fractions. A considerable percentage of radioactivity was found unextractable with the organic solvents, suggesting that styrene oxide reacted with the endogenous compounds. The intracellular distribution of this epoxide was also studied in the perfused rat liver. Comparable results with those previously described were obtained. The binding of styrene oxide to the cytosolic protein was investigated by equilibrium dialysis and ultrafiltration. Only a small percentage of the compound was bound to protein.

Animals↗
PubMed1984

Atenolol and metoprolol. A comparison of their excretion into human breast milk.

The transfer of atenolol and metoprolol to human breast milk was studied in 7 lactating women with hypertension. Concentrations of atenolol and metoprolol in maternal plasma and milk and in plasma of the nursed infants were determined. Blood samples were obtained from the women and from the infants during a dose interval. Milk was collected repeatedly from the left breast but only twice from the right breast. The ratio between the area under the milk concentration versus time curve ( AUCm ) and the area under the plasma concentration versus time curve ( AUCp ) in the mother varied between 2.0 and 3.1 for metoprolol and 1.1 and 3.1 for atenolol. The milk concentrations of metoprolol in the right breast were similar to those in the left breast, although the latter had been emptied more frequently. For atenolol the milk concentrations in the right breast were lower than in the left breast. The plasma concentrations of metoprolol and atenolol in the infants were negligible or below the limit of detection. Our results show that exposure of the infant to metoprolol can be minimized if nursing is not undertaken earlier than 3-4 hours after dose intake.

Atenolol↗
PubMed1984

Comparative determination of sulfonamide concentration in serum by chemical and microbiological assay.

Analysis of sulfamethoxazole in serum from patients treated with trimethoprim-sulfamethoxazole was performed with the agar diffusion assay which is supposed to measure only unconjugated sulfonamide and with the spectrophotometric method which enables one to measure both unconjugated and conjugated sulfonamide. The two methods gave serum concentrations in the same range when used in patients with intact kidney function. In patients with decreased renal function the chemical method yielded higher values, probably due to accumulation of conjugated sulfamethoxazole. The agar diffusion assay gives an accurate answer if the clinical question concerns the therapeutic effect only. The spectrophotometric analytical method has a broader potential since it may be employed irrespective of the clinical question that motivated the analysis.

Adolescent↗
PubMed1984

Amphetamine secretion in breast milk.

The excretion of amphetamine in human breast milk was studied in a nursing mother with narcolepsy, who was treated with 20 mg daily of a racemic preparation of amphetamine. The concentration of amphetamine was 3 and 7 times higher in breast milk than in maternal plasma on the 10th and 42nd days after delivery. Small amounts of amphetamine were found in urine samples from the infant.

Adult↗
PubMed1984

Polymorphic acetylation of 7-amino-clonazepam in human liver cytosol.

The N-acetylation of the reduced metabolite of clonazepam 7-amino-clonazepam was studied in cytosolic preparation from human fetal and adult livers. The metabolite formed 7-acetamido-clonazepam was measured with high performance liquid chromatography. A bimodal distribution of the N-acetyltransferase activities was observed in cytosols from human adult livers. These activities were 117 +/- 11 and 27 +/- 16 pmoles X mg-1 X min-1 for rapid and slow acetylators, respectively. The data observed in the fetal specimens did not allow any conclusion about bimodality because of a low number of samples.

Acetylation↗
PubMed1984

Histone complements of human tissues, carcinomas, and carcinoma-derived cell lines.

The pattern of subtypes of the nucleosomal histones and of histone H1 was investigated in human cells from adult and fetal lung and liver, from carcinoma tissues and from carcinoma-derived cell lines, with the object of comparing these patterns, and their relationship to cell growth rate, with those in cells of other species. The subtype pattern of the nucleosomal histones H2A and H3 shows a correlation with replication rate. In adult tissues, subtype H3-3 predominates over H3-2 and H3-1, and the subtype H2A-1 and H2A-2 are approximately equally abundant. In fetal tissues, lung carcinoma and cultured carcinoma-derived cell lines, the subtype H3-1 is predominant and H2A-1 is more abundant than H2A-2. The subtype pattern of H1 also differs between normal and carcinoma cells, among different tissues, and in different cell lines derived from the same type of carcinoma. In particular, the relative level of H1 degrees differs in several cell lines showing relatively high rates of replication, and in some cases represents more than 25% of the total H1, similar to the level in slowly replicating normal adult liver and lung tissues. The relative level of H1 degrees does not therefore appear to be correlated in a simple manner with cell growth rate in these human cells.

Animals↗