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Biomedical subjects

B Persson

Publications and source records attributed to B Persson.

At least 343 records · Page 19Linked to original sources
PubMed1988

Interrelation between glucose, insulin, C-peptide and 3-hydroxybutyrate in plasma and amniotic fluid in last trimester diabetic women without residual betacell function.

The relationship between maternal plasma and amniotic fluid (AF) concentrations of glucose, insulin, C-peptide and 3-hydroxybutyrate (3-HB) was analysed between 45 to 140 minutes after a standardized breakfast in 8 type I diabetic women without residual betacell function and in 13 nondiabetic control women during the last trimester of gestation. AF levels of both glucose and C-peptide were slightly and AF insulin levels significantly (P less than 0.05) elevated above normal in the diabetic women. 3-HB levels in plasma and in AF were significantly (P less than 0.05) elevated in the diabetic group between 45 to 65 minutes after breakfast. AF insulin and glucose was significantly correlated in the diabetic group (r = 0.96, P less than 0.05). During the 2 hour study period AF levels of glucose, insulin and C-peptide remained essentially unchanged in both groups of women. Changes in maternal plasma 3-HB concentrations seemed to be more rapidly reflected in AF.

3-Hydroxybutyric Acid↗
PubMed1988

Urinary C-peptide in the neonate correlates both to maternal glucose tolerance and to fetal size at birth.

In 18 women with gestational diabetes the variables of an oral glucose tolerance test (fasting and 2-hour blood glucose values and area under the blood glucose curve) performed in the last trimester of pregnancy correlated significantly with the urinary C-peptide excretion during the first 12 hours of the life (r = 0.47, 0.71, and 0.60, respectively). In a combined group with 28 type II pregnant diabetic women there was also a significant correlation between the urinary C-peptide excretion of the infants and their skinfold. Assay of the urinary C-peptide excretion of the neonate, reflecting its insulin production, seems to be a sensitive parameter to study the influence of the maternal carbohydrate metabolism in the offspring.

Birth Weight↗
PubMed1988

Effects of a new serotonin antagonist, ketanserin, in experimental and clinical hypertension.

Ketanserin is an agent whose main pharmacologic action is antagonism of serotonin (5-hydroxytryptamine, 5HT) receptors of the 5HT2 subtype. It also has weak alpha 1-adrenergic blocking properties, which may contribute to the acute blood pressure lowering effects seen in animal models of hypertension. During chronic treatment of hypertension in animals, the 5HT2 antagonistic properties, or a combination of 5HT2 and alpha 1-antagonistic effects, seems to be responsible for ketanserin's hypotensive action. Studies of patients with hypertension have demonstrated the therapeutic effects of ketanserin in monotherapy and combination therapy. In humans, the drug has a terminal half-life of 12-25 hours, and a twice daily dosage will lower blood pressure over the day. Ketanserin is a vasodilator that acts on both resistance and capacitance vessels. Chronic treatment with the drug causes minimal reflex changes in cardiovascular function, as well as sustained blood pressure reduction comparable with the effects of beta-adrenergic blockers or diuretics. In elderly patients, the therapeutic effects of ketanserin appear to be greater, and side effects are less frequent compared with beta-blockers and diuretics. In addition to its antihypertensive action, ketanserin also produces other effects that may be important in reducing cardiovascular morbidity and mortality in patients with hypertension. Some studies have shown a reduction in total and low-density lipoprotein (LDL) cholesterol, and a rise in high-density lipoprotein (HDL) cholesterol. Ketanserin also reduces ex vivo platelet aggregation and inhibits the serotonin-induced platelet release reaction. Worldwide experience with ketanserin in the treatment of hypertension indicates that it is a safe and effective agent for long-term therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

High- and low-dose fentanyl anaesthesia: hormonal and metabolic responses during cholecystectomy.

We have compared two groups of patients given low- or high-dose fentanyl anaesthesia. Arterial blood samples were collected for measurement of glucose, free fatty acids (FFA), glycerol, beta-hydroxy-butyrate, insulin, c-peptide, glucagon, human growth hormone (HGH), cortisol and adrenaline concentrations. After induction of anaesthesia, blood concentrations of most of these substances decreased. After the start of surgery the concentrations of cortisol, glucose, HGH, FFA and beta-hydroxy-butyrate increased significantly in the group anaesthetized with the lower dose of fentanyl. In the group that received high-dose fentanyl anaesthesia the plasma concentrations of almost all the hormones and substances measured remained relatively low. The differences between the two groups during surgery were significant for adrenaline (P less than 0.001) and cortisol (P less than 0.001). High-dose fentanyl appears to block the trauma-induced stress response seen in patients anaesthetized with low dose fentanyl.

Adult↗
PubMed1988

On the presence of a nicotinamide nucleotide transhydrogenase in mitochondria from potato tuber.

Mitochondria isolated from potato (Solanum tuberosum L.) tuber were investigated for the presence of a nicotinamide nucleotide transhydrogenase activity. Submitochondrial particles derived from these mitochondria by sonication catalyzed a reduction of NAD(+) or 3-acetylpyridine-NAD(+) by NADPH, which showed a maximum of about 50 to 150 nanomoles/minute.milligram protein at pH 5 to 6. The K(m) values for 3-acetylpyridine-NAD(+) and NADPH were about 24 and 55 micromolar, respectively. Intact mitochondria showed a negligible activity in the absence of detergents. However, in the presence of detergents the specific activity approached about 30% of that seen with submitochondrial particles. The potato mitochondria transhydrogenase activity was sensitive to trypsin and phenylarsine oxide, both agents that are known to inhibit the mammalian transhydrogenase. Antibodies raised against rat liver transhydrogenase crossreacted with two peptides in potato tuber mitochondrial membranes with a molecular mass of 100 to 115 kilodaltons. The observed transhydrogenase activities may be due to an unspecific activity of dehydrogenases and/or to a genuine transhydrogenase. The activity contributions by NADH dehydrogenases and transhydrogenase to the total transhydrogenase activity were investigated by determining their relative sensitivities to trypsin. It is concluded that, at high or neutral pH, the observed transhydrogenase activity in potato tuber submitochondrial particles is due to the presence of a genuine and specific high molecular weight transhydrogenase. At low pH an unspecific reaction of an NADH dehydrogenase with NADPH contributes to the total trans-hydrogenase activity.

Journal Article↗
PubMed1988

The epidemiology of lost residual beta-cell function in short term diabetic children.

Using the country-wide Swedish childhood diabetes register 526 children, who had had diabetes for 6-30 months were traced for measurements of 24-hour urinary C-peptide. Lost beta-cell function was defined as a 24-hour urinary C-peptide excretion per kg body weight less than 10% of the mean for healthy children (less than 0.025 nmol/kg). The estimated cumulative incidence of lost beta-cell function was 0.64 at 30 months. The incidence of lost beta-cell function did not differ by sex. Neither was there any significant variation in season at onset for cases with lost beta-cell function. A significant age dependency was shown for the cumulative incidence of lost beta-cell function with the highest incidence in the young age groups, i.e. a reversed age dependency compared to that of clinical onset. In contrast to the clinical onset of diabetes no significant geographical variation was found for lost beta-cell function when comparing standardized morbidity ratios. The urinary C-peptide excretion was significantly correlated to age at onset but not to degree or duration of ketonuria at onset. It is concluded that there are striking differences when comparing the epidemiology of lost beta-cell function to that of clinical onset in terms of age, sex, seasonal and geographical variations. The timing of clinical onset may thus partly be determined by factors different from those determining the rate of fall in beta-cell function.

Adolescent↗
PubMed1988

Chronic lymphatic leukaemia and engine exhausts, fresh wood, and DDT: a case-referent study.

The effect of potential risk factors for chronic lymphatic leukaemia was evaluated in a case-referent study encompassing 111 cases and 431 randomised referents, all alive. Information on exposure was obtained by questionnaires posted to the subjects. Crude rate ratios were increased for occupational exposure to solvents. DDT, engine exhausts, fresh wood (lumberjacks, paper pulp workers, and sawmill workers, for example) and also in farming. Further analysis of the material by means of the Miettinen confounder score technique reduced the number of rate ratios significantly exceeding unity to encompass only occupational exposure to engine exhaust, fresh wood, DDT, and contact with horses.

Adult↗
PubMed1988

Smoking exerts a ketogenic influence in diabetic pregnancy.

Acute cardiovascular and metabolic responses to the smoking of two cigarettes were studied in 12 normal and 7 diabetic women in the last trimester of pregnancy. When the responses to smoking were compared between the healthy and diabetic women no statistically significant difference was found except for 3-hydroxybutyric acid where diabetic women but not the normal patients reacted with a pronounced increase. It is concluded that smoking exerts a ketogenic influence in diabetic pregnancy.

Diabetic Ketoacidosis↗
PubMed1988

The effects of biosynthetic insulin-like growth factor-1 supplementation on somatic growth, maturation, and erythropoiesis on the neonatal rat.

Somatomedins are anabolic hormones that may stimulate growth during the perinatal period. To test this hypothesis, neonatal rats were injected with a biosynthetic somatomedin, insulin-like growth factor 1 (IGF-1) twice daily for the first 2 wk of life. Two biosynthetic IGF-1 preparations of different potency were tested as well as a preparation of human growth hormone in five litters of rats. When compared to saline-injected rats, IGF-1 injected rats had increased body weight and tail length as well as specific increases in weights of liver, brain, heart, and testes. In addition, significant increases in bone marrow erythropoietic cell precursors were apparent after IGF-1 injection. IGF-1-treated neonatal rats also exhibited precocious eye opening as a sign of epithelial cell differentiation. Five additional litters of rats received similar injections but were exposed to postnatal nutritional deprivation via artificially increasing litter size. Although IGF-1 caused stimulation of bone marrow erythropoiesis and precocious eye opening, no effects of IGF-1 on somatic or organ growth could be documented. This represents the first demonstration in vivo of the anabolic effects of IGF-1 in rapidly growing neonatal rats but suggests that nutritional sufficiency may also be necessary for the full expression of somatomedin effects.

Animals↗
PubMed1988

Antihypertensive effects of ketanserin and ritanserin in the spontaneously hypertensive rat.

Acute as well as chronic treatment with ketanserin but not with ritanserin reduced the blood pressure in the spontaneously hypertensive rat, indicating that 5-HT2-receptor blockade alone does not have antihypertensive properties. Whereas the blood pressure reduction to acute administration of ketanserin was directly related to its ability to shift the dose-response curve of phenylephrine (alpha 1-adrenergic blockade), the same relationship was not apparent following chronic treatment with ketanserin. This suggests that the 5-HT2- and alpha 1-blockade may complement each other in reducing the blood pressure, a conclusion supported by the observation that in the conscious rat, 5-HT2-receptor blockade by ritanserin enhanced the hypotensive response to prazosin. However, ritanserin did not influence the ability of prazosin to antagonize pressor responses to phenylephrine in the pithed rat.

Animals↗
PubMed1988

Experience with ketanserin and ritanserin in hypertensive patients.

In patients with essential hypertension, ketanserin (40 mg once or twice daily) reduces the blood pressure in mono- and combination therapy. Despite evidence of peripheral vasodilation, the heart rate is reduced. This would suggest that ketanserin has an additional sympathoinhibitory effect. However, the influence of ketanserin on plasma catecholamine levels at rest and during exercise or stress was small, and to date there is little evidence for a central sympathoinhibitory effect of ketanserin in humans. The antihypertensive effects of ritanserin, a selective 5-HT2-receptor antagonist, were investigated in a double-blind, placebo-controlled crossover study (4 weeks). Treatment with ritanserin, 10 mg twice daily, was ineffective in hypertensive patients, which indirectly suggests that the 5-HT2-blocking properties of ketanserin cannot alone be responsible for its antihypertensive effects.

Antihypertensive Agents↗
PubMed1988

Are there reasons to believe that the antihypertensive effects of serotonin (S2) antagonists are age-related?

The potential age-dependent antihypertensive responses to serotonin antagonists are critically reviewed with regard to the following considerations: Are they beneficial to the patient? Are they related to age-dependent changes in pharmacokinetics or pharmacodynamics? Are they necessarily true? The paper is focused on ketanserin, which is the only major serotonin (S2) antagonist that has yet been used to any extent in patients. Based on the available data in the literature, we conclude that the age-related antihypertensive effect of ketanserin is a beneficial phenomenon since it does not seem to be paralleled by a corresponding increase in side effects. Furthermore, the mechanism seems to be due to changes in the pharmacodynamics of the drug on the platelet or vascular smooth muscle since there is only negligible alteration in pharmacokinetics occurring with advanced age. Although multiple independent trials or pooled data strongly indicate that the efficacy of ketanserin increases with age, not all investigators agree. In our opinion, the interindividual variation in drug response is more characteristic to the drug than the relationship to age. Therefore, the selection of patients for ketanserin therapy should be based on individual testing in addition to age grouping.

Aged↗
PubMed1988

Structural classes of glutathione transferase: distinctions between isoenzymes and enzymes.

The amino acid sequences of the five cytosolic rat glutathione transferases 1-1, 2-2, 3-3, 4-4, and 7-7 of three different classes have been compared. Alignments demonstrate 68%-78% positional identity between isoenzymes within the same class, and 29%-32% between the enzymes of different classes. Of the 209-221 residues in the structures, those strictly conserved are limited to 24, over half of which are charged residues and Leu, while few are Gly and Pro that in related proteins otherwise are often maintained because of space restrictions and conserved conformations. In spite of the limited sequence homologies, hydropathy profiles and predictions of secondary structures emphasize the relationship between the three enzyme classes. The predictions indicate alternating alpha-helices and beta-strands, a chain fold typical for alpha/beta protein structures. Glutathione transferases within a class are highly similar and may be regarded as true isoenzymes, while transferases of different classes appear to occupy an intermediate stage between isoenzymes and discrete enzymes.

Amino Acid Sequence↗
PubMed1987

ATP-driven transhydrogenase provides an example of delocalized chemiosmotic coupling in reconstituted vesicles and in submitochondrial particles.

The mechanism of coupling between mitochondrial ATPase (EC 3.6.1.3) and nicotinamide nucleotide transhydrogenase (EC 1.6.1.1) was studied in reconstituted liposomes containing both purified enzymes and compared with their behavior in submitochondrial particles. In order to investigate the mode of coupling between the transhydrogenase and the ATPase by the double-inhibitor and inhibitor-uncoupler methods, suitable inhibitors of transhydrogenase and ATPase were selected. Phenylarsine oxide and A3'-O-(3-(N-(4-azido-2-nitrophenyl)amino)propionyl)-NAD+ were used as transhydrogenase inhibitors, whereas of the various ATPase inhibitors tested aurovertin was found to be the most convenient. The inhibition of the ATP-driven transhydrogenase activity was proportional to the inhibition of both the ATPase and the transhydrogenase. Inhibitor-uncoupler titrations showed an increased sensitivity of the coupled reaction towards carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP)--an uncoupler that preferentially uncouples localized interactions, according to Herweijer et al. (Biochim. Biophys. Acta 849 (1986) 276-287)--when the primary pump was partially inhibited. However, when the secondary pump was partially inhibited the sensitivity towards FCCP remained unchanged. Similar results were obtained with submitochondrial particles. These results are in contrast to those obtained previously with the ATP-driven reverse electron flow. In addition, the amount of uncoupler required for uncoupling of the ATP-driven transhydrogenase was found to be similar to that required for the stimulation of the ATPase activity, both in reconstituted vesicles and in submitochondrial particles. Uncoupling of reversed electron flow to NAD+ required much less uncoupler. On the basis of these results, it is proposed that, in agreement with the chemiosmotic model, the interaction between ATPase and transhydrogenase in reconstituted vesicles as well as in submitochondrial particles occurs through the delta mu H+. In contrast, the energy transfer between ATPase and NADH-ubiquinone oxidoreductase appears to occur via a more direct interaction, according to the above-mentioned results by Herweijer et al.

Adenosine Triphosphatases↗
PubMed1987

Characteristics of alcohol/polyol dehydrogenases. The zinc-containing long-chain alcohol dehydrogenases.

Sixteen characterized alcohol dehydrogenases and one sorbitol dehydrogenase have been aligned. The proteins represent two formally different enzyme activities (EC 1.1.1.1 and EC 1.1.1.14), three different types of molecule (dimeric alcohol dehydrogenase, tetrameric alcohol dehydrogenase, tetrameric sorbitol dehydrogenase), metalloproteins with different zinc contents (1 or 2 atoms per subunit), and polypeptide chains from different kingdoms and orders (mammals, higher plants, fungus, yeasts). Present comparisons utilizing all 17 forms reveal extensive variations in alcohol dehydrogenase, but with evolutionary changes that are of the same order in different branches and at different times. They emphasize the general importance of particular residues, suggesting related overall functional constraints in the molecules. The comparisons also define a few coincidences between intron positions in the genes and gap positions in the gene products. Only 22 residues are strictly conserved; half of these are Gly, and most of the remaining ones are Pro or acidic residues. No basic residue, no straight-chain hydrophobic residues, no aromatic residues, and essentially no branched-chain or polar neutral residues are invariable. Tentative consensus sequences were calculated, defining 13 additional residues likely to be typical of but not invariant among the alcohol dehydrogenases. These show a predominance of Val, charged residues, and Gly. Combined, the comparisons, which are particularly relevant to the data base for protein engineering, illustrate the requirements for functionally important binding interactions, and the extent of space restrictions in proteins with related overall conformations and functions.

Alcohol Dehydrogenase↗
PubMed1987

Energy-linked nicotinamide-nucleotide transhydrogenase. Characterization of reconstituted ATP-driven transhydrogenase from beef heart mitochondria.

The interaction between pure transhydrogenase and ATPase (Complex V) from beef heart mitochondria was investigated with transhydrogenase-ATPase vesicles in which the two proteins were co-reconstituted by dialysis or dilution procedures. In addition to phosphatidylcholine and phosphatidylethanolamine, reconstitution required phosphatidylserine and lysophosphatidylcholine. Transhydrogenase-ATPase vesicles catalyzed a 20-30-fold stimulation of the reduction of NADP+ or thio-NADP+ by NADH and a 70-fold shift of the apparent equilibrium expressed as the nicotinamide nucleotide ratio [NADPH][NAD+]/[NADP+][NADH]. In both of these respects, the transhydrogenase-ATPase vesicles were severalfold more efficient than beef heart submitochondrial particles. By measuring the ATP-driven transhydrogenase and the oligomycin-sensitive ATPase activities simultaneously and under the same conditions at low ATP concentrations, i.e. below 15 microM, the ATP-driven transhydrogenase/oligomycin-sensitive ATPase activity ratio was found to be about 3. This value is consistent with the stoichiometries of three protons translocated per ATP hydrolyzed and one proton translocated per NADPH formed and with a mechanism where the two enzymes interact through a delocalized proton-motive force.

Adenosine Triphosphate↗