PubMed Health⌕ Search

Biomedical subjects

J Kallio

Publications and source records attributed to J Kallio.

33 records · Page 2Linked to original sources
PubMed1998

Antenatal dexamethasone treatment decreases plasma catecholamine levels in preterm infants.

Antenatal corticosteroid therapy (ACT) has many beneficial effects on preterm infants. The cellular mechanisms of action of ACT include beta-adrenergic receptor-mediated cAMP generation. This study investigated the effects of ACT on sympathoadrenal mechanisms during immediate postnatal adaptation of preterm infants. Plasma epinephrine, norepinephrine, 3,4-dihydroxyphenylglycol, and cAMP were measured within 12 h after birth in 103 preterm infants (gestational age 24-36 wk), who were divided into two groups (non-ACT and ACT group) according to whether the mother had received dexamethasone treatment. Infants in the ACT group had significantly lower concentrations of plasma catecholamines than infants in the non-ACT group; plasma epinephrine was 38% lower, and plasma norepinephrine was 20-40% lower in the ACT group, depending on gestational age (r = -0.37 in the non-ACT group and r = -0.28 in the ACT group, p < 0.05). Plasma cAMP concentrations were similar in the two groups. Antihypertensive treatment of the mother was associated with low plasma cAMP (p < 0.001), whereas tocolytic treatment was associated with high plasma cAMP (p = 0.001) of the infant. The results indicate that ACT attenuates the birth-related increase in plasma catecholamines. Still, plasma cAMP levels remain high, which suggests enhanced beta-adrenoceptor signaling after ACT.

Antihypertensive Agents↗
PubMed1997

Subtype specific recognition of human alpha2C2 adrenergic receptor using monoclonal antibodies against the third intracellular loop.

Monoclonal antibodies (Mabs) against human alpha2C2-adrenergic receptor (alpha2C2-AR) were raised in mice and characterized. Bacterially expressed fusion protein consisting a sequence from the putative third intracellular loop (amino acids 213-343) of human alpha2C2 and glutathione-S-transferase (GST) was used as antigen. Results from mass spectrometry of purified thrombin cleaved alpha2C2 polypeptide suggested that the epitope region would lie near the aminoterminal end of the 3rd intracellular loop of human alpha2C2-AR. Elevation of Mabs was detected with Western blotting from mouse blood samples. Three alpha2C2 specific cell clones were expanded to in vitro production in hollow fiber systems. The specificity of the Mabs was further determined by immunoprecipitation and immunocytochemistry. Scatchard analysis of thrombin digested, purified, Europium-labelled antigen (amino acids 213-343 of alpha2C2) revealed binding affinity constants of 0.4 x 10(9), 0.7 x 10(9) and 1.6 x 10(9) M(-1) and Kds of 2.6, 1.4 and 0.6 nM for the three Mabs 2B1, 3G3 and 7G1, respectively.

Amino Acid Sequence↗
PubMed1997

Subtype-specific intracellular trafficking of alpha2-adrenergic receptors.

The three alpha2-adrenergic receptor subtypes (alpha2a, alpha2b, and alpha2c) are highly homologous G protein-coupled receptors. These receptors all couple to pertussis toxin-sensitive G proteins and have relatively similar pharmacological properties. To further explore functional differences between these receptors, we used immunocytochemical techniques to compare the ability of the three alpha2-receptor subtypes to undergo agonist-mediated internalization. The alpha2a-receptor does not internalize after agonist treatment. In contrast, we observed that the alpha2b-receptor is able to undergo agonist-induced internalization and seems to follow the same endosomal pathway used by the beta2-adrenergic receptor. Attempts to examine internalization of the alpha2c-receptor were complicated by the fact that the majority of the alpha2c receptor resides in the endoplasmic reticulum and cis/media Golgi and there is relatively little cell surface localization. Nevertheless, we were able to detect some internalization of the alpha2c-receptor after prolonged agonist treatment. However, we observed no significant movement of alpha2c-receptor from the intracellular pool to the plasma membrane during a 4-hr treatment of cells with cycloheximide, suggesting that these cells are unable to process alpha2c-receptors in the same way they process the alpha2a or alpha2b subtypes.

Amino Acid Sequence↗
PubMed1992

Specific hybridization probes for mouse alpha 2(IX) and alpha 1(X) collagen mRNAs.

We have used polymerase chain reaction (PCR) technology and available cross-species sequence information to construct cDNA probes for mouse alpha 2(IX) and alpha 1(X) collagen transcripts. Sequencing confirmed the identification of the clones. Northern analysis proved sufficient divergence of the cloned sequences from other collagen transcripts: specific detection of the mouse 2.9 kb alpha 2(IX) and 3.3 kb alpha 1(X) collagen mRNAs was seen under normal hybridization and washing conditions.

Amino Acid Sequence↗
PubMed1991

Debrisoquine oxidation in Parkinson's disease.

Variations in the activities of xenobiotic metabolizing liver enzymes may be involved in the pathophysiology of diseases, including Parkinson's disease. We therefore studied the activity of the debrisoquine metabolizing enzyme in 97 patients with newly diagnosed Parkinson's disease. The urine debrisoquine metabolic ratios (MR) of the patients were compared with a group of 176 healthy subjects. There were 4 poor metabolizers (4.1%) among the parkinsonians. This proportion did not differ from that found in the group of healthy subjects (51%). In contrast to earlier finding, the parkinsonian poor metabolizers (PM) had the onset of the disease later than the parkinsonian extensive metabolizers (EM). In the parkinsonian patients, it was observed that the excretion of debrisoquine and 4-OH-debrisoquine into urine correlated inversely with the actual age and age at disease onset. Our results indicate that in patients with Parkinson's disease, debrisoquine hydroxylation is comparable with healthy subjects.

Adult↗
PubMed1990

The relationship between debrisoquine oxidation phenotype and the pharmacokinetics of chlorpropamide.

The pharmacokinetics and urinary metabolite pattern of a single oral dose of chlorpropamide 250 mg have been studied in 6 extensive and 5 poor metabolizers of debrisoquine. Ammonium chloride was given orally to acidify the urine in order to make elimination of the parent drug dependent on metabolism alone. The concentration profile in serum and the pharmacokinetic parameters of the parent drug were similar in both groups. However, the ratio in urine of unchanged chlorpropamide to its hydroxylated metabolites was higher in poor than in extensive metabolizers.

Adult↗
PubMed1990

The effects of beta-adrenoceptor antagonists and levomepromazine on the metabolic ratio of debrisoquine.

The in vivo inhibitory effect of five beta-adrenoceptor antagonists and levomepromazine on debrisoquine metabolism was assessed in 37 subjects. The debrisoquine phenotyping test was performed before and after 7 days' treatment with oxprenolol (40 mg three times daily), propranolol (20 mg three times daily), timolol (10 mg twice daily), pindolol (5 mg twice daily), metoprolol (50 mg twice daily) or levomepromazine (10 mg daily), each of which was given to six-seven subjects. No clear change in the urinary metabolic ratio of debrisoquine/4-OH-debrisoquine (MR) was seen with any of the single beta-adrenoceptor antagonist treatments, but the MR value increased significantly when all beta-adrenoceptor blocker treatments were considered together. Debrisoquine metabolism was clearly impaired after levomepromazine 10 mg daily for 7 days; the mean MR increased from 1.24 +/- 1.6 to 4.70 +/- 5.23 (P = 0.018) and the excretion of 4-hydroxydebrisoquine decreased from 0.92 +/- 0.46 mg to 0.31 +/- 0.19 mg (P = 0.043). Thus, levomepromazine changes MRs towards those characteristic of phenotypically poor metabolizers, but beta-adrenoceptor antagonists at the doses examined have only a marginal effect.

Adrenergic beta-Antagonists↗
PubMed1990

Debrisoquine hydroxylation polymorphism in diabetic patients.

Debrisoquine hydroxylation was assessed in 54 type I and in 42 type II diabetic patients. The distribution of metabolic ratio debrisoquine/4-hydroxydebrisoquine (MR) in urine of the patients was compared with a MR-distribution of 176 healthy subjects, and the correlation of glucose balance parameters with the MR was investigated. One poor metabolizer of debrisoquine was found among type I diabetics but no poor metabolizers were found among type II diabetics. Despite the low frequency of the poor metabolizers, the prevalences of debrisoquine hydroxylation phenotypes did not differ from that in healthy volunteers in either diabetic group. No correlation was found between MR and fasting blood glucose or blood glycosylated hemoglobin A1c, whereas a negative correlation was evident between age and the excretion of 4-hydroxydebrisoquine in urine. In summary, debrisoquine hydroxylation is essentially unaltered in type I and type II diabetes mellitus, and no relationship exists between debrisoquine hydroxylation and glucose balance.

Adult↗
PubMed1990

The effect of urine pH on debrisoquine phenotyping: application of an HPLC-method.

The effect of urine pH on debrisoquine metabolic ratio (MR) was studied in 6 healthy volunteers. They were phenotyped on two separate occasions, firstly when urine was made alkaline with orally given sodium bicarbonate, and secondly when urine was acidified with oral ammonium chloride. The concentrations of debrisoquine and 4-hydroxydebrisoquine were analyzed by an HPLC (high performance liquid chromatographic) method, which was compared with a standard GC (gas chromatographic) method. The calculated MRs proved to be similar during alkalinization and during acidification, although there was a tendency to lower excretion of debrisoquine and its 4-hydroxymetabolite into acidic urine. The HPLC analysis correlated well with the GC analysis of debrisoquine and 4-hydroxy-debrisoquine concentrations in urine. The debrisoquine MRs obtained with HPLC and GC also correlated favorably (r = 0.90, p less than 0.001).

Administration, Oral↗
PubMed1989

Inhibition of monoamine oxidase by moclobemide: effects on monoamine metabolism and secretion of anterior pituitary hormones and cortisol in healthy volunteers.

1. Single oral doses (100, 200 and 300 mg) of moclobemide, a reversible inhibitor of monoamine oxidase (MAO) with predominant effects on the A-type of the enzyme, were administered to eight young, healthy male volunteers in a double-blind, random-order, placebo-controlled study. The investigation was thereafter continued in an open fashion by administering a single 10 mg dose of the MAO-B inhibitor deprenyl to the same subjects. 2. Deamination of catecholamines was powerfully and dose-dependently inhibited by moclobemide, as evidenced by up to 40% decreases in the urinary excretion of deaminated catecholamine metabolites, corresponding increases in the excretion of non-deaminated, methylated metabolites, and up to 79% average decreases in the plasma concentration of 3,4-dihydroxyphenylglycol (DHPG), a deaminated metabolite of noradrenaline (NA), and up to 75% average decreases in the plasma concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC), a deaminated metabolite of dopamine. The urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) was only slightly reduced. In contrast, deprenyl, in a dose which almost totally inhibited MAO-B activity in blood platelets, did not appreciably affect the plasma concentrations of DHPG or DOPAC. 3. Due to the rapid, reversible, dose-dependent and MAO-A specific effect of moclobemide on plasma concentrations of DHPG, it is suggested that DHPG in plasma may be a useful indicator of the magnitude and duration of MAO-A inhibition in man. 4. Sympatho-adrenal function at rest was not significantly altered by moclobemide, as judged by unchanged plasma catecholamine concentrations and stable blood pressure and heart rate recordings. 5. Monoamine oxidase type B activity in blood platelets was slightly (less than 30%) and transiently inhibited after moclobemide. 6. The secretion of prolactin was dose-dependently stimulated by moclobemide, whereas the plasma concentrations of growth hormone (hGH) and cortisol remained unchanged.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Debrisoquine oxidation in a Finnish population: the effect of oral contraceptives on the metabolic ratio.

1. The debrisoquine hydroxylation phenotype was assessed in 211 healthy subjects of Finnish Caucasian origin. 2. A bimodal distribution was observed in the urinary debrisoquine/4-hydroxydebrisoquin ratio. Eleven subjects (about 5%) were poor metabolizers of debrisoquine, when a ratio of 12.6 was used as the cut-off point. 3. The mean metabolic ratio of 35 extensive metabolizers taking oral contraceptives was slightly lower than that of extensive metabolizers not taking contraceptives. This indicates that oral contraceptives may change the phenotyping near the metabolic ratio of 12.6. 4. The metabolic ratios were determined in eight subjects using both 4 h and 6 h urine collection times. The metabolic ratios corresponded well with each other indicating the usefulness of the shorter 4 h collection time.

Adult↗
PubMed1986

Inhibitory effects of neuroleptics on debrisoquine oxidation in man.

Liver oxidative metabolism, assessed by debrisoquine hydroxylation test, was studied in 107 healthy volunteers and in 71 patients with or without neuroleptic drug treatment. The mean metabolic ratio (MR = debrisoquine/4-hydroxydebrisoquine excretion in the urine) was 2.8 +/- 0.1 (s.e. mean) in the control group, six persons being poor metabolizers of debrisoquine (MR greater than or equal to 12.6). The mean MR (12.1 +/- 1.5) was significantly higher in those 42 patients taking neuroleptics than in patients without neuroleptics (0.8 +/- 0.1). In the former group, seventeen patients had a MR exceeding 12.6. Oral contraceptives, antiepileptics, benzodiazepines and progestin derivates did not increase MR values, the highest individual ratio being 2.72 in those subjects not receiving neuroleptics. These results suggest a probable competitive inhibition of oxidative metabolism by neuroleptics. This is a phenomenon of potential clinical importance both in patients with an inherited poor metabolic capacity and in patients receiving other drugs like beta-adrenoceptor blocking agents and tricyclic antidepressants oxidized by the same enzyme system.

Adolescent↗
PubMedDate not supplied

Transurethral prostatectomy in patients with preoperative bacteriuria: double-blind study with oral fleroxacin and cefalexin.

We compared oral fleroxacin and cefalexin in the prevention of postoperative infectious complications after transurethral prostatectomy (TURP) in patients with preoperative bacteriuria. 95 patients underwent TURP due to benign prostatic hyperplasia with preoperative bacteriuria. The therapy consisted of 7 days of oral fleroxacin 400 mg once a day or cefalexin 500 mg three times daily. After 2 weeks, 62% of the urine samples were sterile in the fleroxacin groups but only 37% in the cefalexin group (p = 0.047). Patients in the cefalexin group had also statistically significantly more symptoms of urinary tract infections. After 6 weeks, the bacterial eradication rate was 53% in the fleroxacin group and 37% in the cefalexin group. There were no septicemias. TURP can be performed with reasonable safety with this oral antibiotic therapy.

Administration, Oral↗