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Biomedical subjects

G Ronquist

Publications and source records attributed to G Ronquist.

At least 127 records · Page 7Linked to original sources

Sickle cell anaemia in Sudan: clinical findings, haematological and serum variables.

Ninety homozygous patients with Hb S haemoglobinopathy from Sudan were reported with respect to clinical findings, haematological and serum parameters. For comparison, 27 Hb AS heterozygous subjects and 28 Hb AA controls were investigated also. The patients showed an extreme type of illness presenting with severe clinical signs such as dactylitis, liver enlargement and cardiac complications. There was marked haemolytic anaemia (mean haemoglobin 66 g/l). Some patients also presented with low serum (S)-iron levels, indicating iron deficiency. S-bilirubin, S-ASAT, S-ALAT, S-GT and S-urate were notably raised, most probably as a consequence of haemolysis with liver involvement. The patients had lower S-calcium levels when compared with the AS and AA subjects. This may suggest a possible role of HB S in the production of this feature.

Adolescent↗

Decreased erythrocyte cholesterol/phospholipid ratio in untreated patients with essential hypertension.

The erythrocyte cholesterol/phospholipid ratio was determined in eight patients with untreated essential hypertension and compared with that of eight age-matched control subjects. The ratio was significantly lower in patients (Wilcoxon's paired rank test; P less than 0.01), and a correlation existed between the ratio and serum cholesterol concentration in patients (r = 0.63) but not in controls (r = 0.02). A reduction in the cholesterol/phospholipid ratio may play a direct role in destabilizing the plasma membrane, which will in turn result in an increase in membrane permeability in essential hypertension.

Adult↗

Angina pectoris patients with normal coronary angiograms but abnormal thallium perfusion scan exhibit low myocardial and skeletal muscle energy charge.

Seven patients with angina pectoris and 201-thallium scintigraphy indicative of myocardial perfusion defects, but with normal coronary angiograms, were investigated. Metabolic events were studied in biopsies from myocardium and skeletal muscle (m. quadriceps femoris). Profound metabolic derangement was evidenced by a distinctly lowered energy charge in myocardium (0.88 +/- 0.04 in controls vs. 0.48 +/- 0.09 in patients; P less than 0.001) and skeletal muscle (0.92 +/- 0.01 in controls vs. 0.70 +/- 0.09 in patients; P less than 0.01). Accordingly, low values were recorded for ATP in both types of muscle, where ATP was lower than (myocardium) or the same as (skeletal muscle) ADP. The concentration of myocardial lactate was 115 +/- 74 mumol g-1 dry weight and that of skeletal muscle lactate was 11 +/- 3 mumol g-1 dry weight, compared to normal myocardial lactate of 18 +/- 10 mumol g-1 dry weight and normal skeletal muscle lactate of 11 +/- 3 mumol g-1 dry weight. Unprecedentedly low energy charge levels in both cardiac and skeletal muscle biopsies suggest that a systemic metabolic disease is highly probable. An inverse ATP/ADP ratio found in our patients is indicative of an aetiology different from ischaemia, which would not produce this relationship.

Adenosine Diphosphate↗

Inhibition of Zn(2+)-dependent ATPase in prostasome membrane by nonsaturated, long-chain fatty acids.

Arachidonic and oleic acids, opposite to stearic and palmitic acids, at concentrations near 10(-5) mol/l markedly inhibited Zn(2+)-dependent ATPase in human prostasome membranes. Arachidonic acid was somewhat more potent as inhibitor than oleic acid and the involvement of the metabolites of arachidonic acid cascade was less probable. Deoxycholate, an anionic biological detergent, produced a similar inhibitory effect although at a much higher concentration. The restraining role of nonsaturated, long-chain fatty acids on sperm motility in human semen is discussed in terms of their established inhibitory action on prostasome ATPase systems.

Adenosine Triphosphatases↗

Central nervous system damage during cardiac surgery assessed by 3 different biochemical markers in cerebrospinal fluid.

Three cerebral biochemical markers, adenylate kinase (AK), neuron-specific enolase (NSE) and protein S-100, were determined in the cerebrospinal fluid (CSF) of male patients 24 h after coronary artery bypass grafting to investigate the extent of possible center nervous system (CNS) damage and relation to the type of oxygenator and the use of an arterial line filter. The patients were randomized into three groups for extracorporeal circulation (ECC); bubble oxygenator without an arterial line filter (Group I, n = 30), bubble oxygenator with a filter (Group II, n = 29) and a flat-sheet membrane oxygenator without a filter (Group III, n = 33). Pathologically high CSF levels of AK and NSE were found 24 h after ECC in respectively 93% and 95% of the patients. All protein S-100 concentrations were within the normal range. Isolated high CSF concentrations of AK, NSE and protein S-100 were observed in group I. Levels of AK and NSE were the lowest in group III, although there was no statistical difference between the groups. In conclusion, our study suggested that CNS damage caused by ECC involved neurons rather than glial cells. AK and NSE in the CSF seemed to be markers of ischaemic neuronal damage. Postoperative levels of biochemical markers in the CSF tended to be the lowest in the flat-sheet membrane oxygenator group.

Adenylyl Cyclases↗

Regional differences in energy charge of the pregnant human uterus regardless of functional status in comparison with the non-pregnant uterus.

The energy status of the cell is mainly dependent on adenine nucleotides and can be expressed as energy charge (EC). EC is known to be kept at narrow limits near 0.90 under normal conditions in most cells. We recently reported remarkably low EC values in the human uterus under apparent steady-state conditions. The present paper is an extension of previous work. It shows that EC varies in different regions of the uterus in that the isthmic part in pregnant women displays a higher EC than the fundus of the uterus. There were no intergroup differences between non-pregnant and term pregnant women, nor between those who were in active normal labour, dysfunctional labour or those who were not in labour at all. On the other hand, EC in uterine muscle of post-menopausal women showed a significantly lower EC value. Human uterus seems to manage its metabolic requirements under different functional conditions in spite of low ATP and EC values. This suggests that ATP occurs in sufficient amounts to pertinent enzyme reactions, especially ATPases, which means Km values adapted for this unusually low ATP concentration.

Adenosine Triphosphatases↗

Dopamine and high-dose insulin infusion (glucose-insulin-potassium) after a cardiac operation: effects on myocardial metabolism.

Myocardial insulin resistance, in association with surgical stress, restricts the availability of carbohydrates and increases the load of free fatty acids (FFAs) on the heart. On theoretical grounds adrenergic drugs may be expected to aggravate this situation, whereas the opposite is expected from insulin. The influence of dopamine and a combination of dopamine (7 micrograms/kg body weight/min) and high-dose insulin (7 IU/kg) on myocardial energy metabolism was studied in 19 patients 4 to 6 hours after a coronary operation. Infusion of dopamine (7 micrograms/kg body weight/min) induced metabolic changes that may be unfavorable to the strained myocardium. There was an increase of the myocardial FFA load and a rise in myocardial oxygen expenditure by 60% to 70%. There changes were, however, not matched by an increase in myocardial substrate uptake. "Oxygen wastage" of FFA metabolism at high circulating catecholamine levels is suggested. There were also signs suggesting an amplified systemic trauma response: systemic oxygen consumption increased by 15%, and an increase in the arterial levels of FFAs, glucose, and ketones was observed. Divergent metabolic effects of dopamine and insulin were demonstrated. The most prominent metabolic effects of adding high-dose insulin to dopamine were a marked reduction of arterial FFA levels and a shift toward myocardial carbohydrate utilization at the expense of FFAs. Myocardial uptake of FFAs ceased. Myocardial insulin resistance may thus to a significant extent be overcome by supraphysiological doses of insulin, even during infusion of adrenergic drugs.

Adult↗

Muscle ATP and lactate and the release of myoglobin and carbanhydrase III in acute lower-limb ischaemia.

Serum-myoglobin and carbanhydrase III (S-CAIII), a specific muscle enzyme, were measured on admission, during surgery and in the postoperative period in 23 patients with acute lower-limb ischaemia and in 21 patients with chronic limb ischaemia in order to evaluate these molecules as possible markers of the degree of clinical ischaemia. The muscle contents of ATP and lactate were determined in muscle biopsies from patients with acute ischaemia on admission. Unlike S-myoglobin and S-CAIII they discriminated between cases which required subsequent amputation from those which did not. Clinical signs of ischaemia were, however, of no value in this respect and there were no correlations between clinical signs or the duration of ischaemia and S-myoglobin or S-CAIII or the contents of ATP or lactate in muscle tissue. The levels of S-myoglobin and S-CAIII correlated well (r = 0.95, p less than 0.0001). In patients who subsequently required an amputation S-myoglobin increased ten-fold (i.e., from 24-48 h postoperatively in acute arterial ischaemia and from 3 h postoperatively in patients with chronic limb ischaemia). In patients with a successful revascularisation S-myoglobin returned to normal levels. It is concluded that in this investigation S-myoglobin had no prognostic value on admission and that S-myoglobin analyses in the postoperative course may be useful for making clinical decisions concerning impending recirculation failures.

Acute Disease↗

Phospholipase A activity in seminal plasma of men attending an infertility clinic.

Seminal plasma from 40 men attending an infertility clinic was analyzed for phospholipase A activity and compared with serum from 20 healthy blood donors. The imprecision of the method was acceptable and the overall coefficient of variation was 8.1%. A huge discrepancy existed between seminal plasma and blood serum with regard to phospholipase A activity, the former fluid displaying on average a 180-fold higher activity than the latter. Preincubation of seminal plasma for 1 h at 37 degrees C resulted in an even higher phospholipase A activity while the corresponding activity in serum remained unchanged by such a treatment. This suggested the existence of a zymogen form of phospholipase A in seminal plasma. A significant correlation existed between sperm concentration and phospholipase A activity in seminal plasma (r = 0.46; p less than 0.01) and preincubated seminal plasma samples from normozoospermic men displayed a significantly higher mean value than those of azoospermic men. Phospholipase A activity also correlated significantly to zinc concentration in seminal plasma (r = 0.67; p less than 0.001). 4-Bromophenacyl bromide was inhibitory to a certain extent, the inhibition being most evident in the samples with high phospholipase A activity. Dibucaine and quinacrine, known phospholipase inhibitors in other systems, had no inhibitory effects. Only 58% of the seminal plasma samples contained measurable amounts of triglycerides. No significant correlation existed between triglyceride concentration and phospholipase A activity, r = 0.11.

Acetophenones↗

Uridine, xanthine and urate concentrations in prostatic fluid and seminal plasma of patients with prostatitis.

The etiology of prostatitis is not fully understood and several causative factors have been considered in the past. In this study we analyzed the expressed prostatic secretion (EPS) and seminal plasma with regard to uridine, xanthine, urate, creatinine and zinc from patients with prostatitis (the diagnosis was based on symptoms for at least 1 year), together with creatinine, urate and zinc in the serum. In 8 of the patients, a direct comparison of these constituents was performed between EPS and seminal plasma. EPS contained low concentrations of uridine and xanthine and high concentrations of creatinine and zinc as opposed to seminal plasma that displayed a reverse pattern. The mean urate concentration in seminal plasma, exceeding that of EPS by 78%, was rather close to the mean value found in serum but no significant correlation was seen between urate in serum and urate in seminal plasma or EPS. Urate in EPS correlated significantly to xanthine in EPS and such a relationship was also observed between urate and creatinine in EPS. In seminal plasma, urate and xanthine were likewise correlated with each other. On division of the patients into a high-score symptom group and a low-score group, no intergroup differences were found in EPS and seminal plasma constituents. Hence, we found high concentrations especially of uridine and xanthine in seminal plasma, compared with other body fluids, and evidence of a backflow of urine mixing with the prostatic fluid of these patients was seen. We suggest that crystal formation of these metabolites may occur under certain conditions and could constitute a first step in the development of prostatitis-vesiculitis-epididymitis in some cases.

Adult↗

Reduction in band 3 protein of red cells in sickle cell anaemia.

Twelve patients suffering from sickle cell anaemia (Hb less than 75 g/l) with SS-haemoglobin were studied with special regard to Band 3-protein content in their erythrocyte membranes on SDS-PAGE. They were compared in this respect with 7 asymptomatic individuals with AS-haemoglobin and 10 healthy controls with the ordinary adult haemoglobin. A heterogeneity in Band 3-protein content was evident among the 12 patients. Six of them belonged to a low content group while the other 6 belonged to a high content group comparable with the asymptomatic subjects and the controls. No simple relationship seemed to exist between Band 3-protein reduction and the clinical presentation.

Adolescent↗

Effects of adenosine infusion on the pig heart during normothermic ischemia and reperfusion.

Possible enhancement of myocardial protection during ischemia and reperfusion by administration of adenosine was evaluated in a pig heart model. Adenosine (100 micrograms/kg/min) was infused into the aortic root during ischemia in group AI (n = 5) and into the right atrium during reperfusion in group AR (n = 6). Group C (n = 6) served as controls. During cardiopulmonary bypass the hearts were subjected to 30 min of normothermic ischemia and 15 min of reperfusion before weaning. In group AI the stroke work index 30 and 90 min after ischemia and the mean arterial pressure 30 min after ischemia were significantly higher than in group C. These parameters did not differ significantly between groups AR and C. All groups showed decrease in myocardial adenosine triphosphate (ATP) and adenylate charge potential (ACP) during ischemia and partial (ATP) or complete (ACP) restoration after ischemia. Adenosine infusion into the aortic root during ischemia (adenosine cardioplegia) thus resulted in improved postischemic heart function, although biochemical correlates in ATP and ACP were not apparent.

Adenosine↗

Myocardial uptake of amino acids and other substrates in relation to myocardial oxygen consumption four hours after cardiac operations.

Myocardial metabolism seems to be markedly abnormal during the first hours of reperfusion after aortic crossclamping. Thus we previously demonstrated no uptake of carbohydrate or lipid substrates 1 hour after coronary operations. Amino acids were the only exogenous substrates taken up by the heart. The aim of the present study was to examine if this metabolic abnormality persisted a few hours later. This was done by measuring coronary sinus blood flow and arterial-coronary sinus differences of oxygen, glucose, free fatty acids, glycerol, lactate, beta-OH-butyrate, and amino acids in a similar group of 19 patients 4 to 5 hours after coronary operations. The results demonstrate a change toward normalization of myocardial free fatty acid use, although the threshold for free fatty acid uptake seemed elevated in comparison with that in the normal postabsorptive state. No correlation was found between free fatty acid uptake and myocardial oxygen consumption. Despite elevated arterial levels of glucose, lactate, pyruvate, and beta-OH-butyrate, no uptake was observed. Myocardial amino acid exchange demonstrated a pattern suggestive of postischemic metabolic adaptation. Several amino acids were extracted, glutamate and branched chain amino acids being the quantitatively most important. The uptake of glutamate and branched chain amino acids correlated with myocardial oxygen consumption, which suggests a direct link to myocardial energy metabolism. Myocardial glutamate uptake seemed to be limited by substrate availability.

3-Hydroxybutyric Acid↗

Analysis of free inositol trisphosphate in heart tissue by FPLC and isotachophoresis.

Recent, increasing interest in inositol tris(1,4,5)phosphate (IP3) turnover and metabolism has led to a need for a fast and quantitative determination of this compound in various tissues. These requirements are fulfilled by separation in different steps (FPLC and Sephadex G-10) culminating in further separation and quantification by isotachophoresis. Isotachophoresis means a migration of ion species of the same sign in an electrical field with all ions moving with the same velocity. The migration takes place when an electrical field is applied to a system of electrolytes of specific design. Detection was carried out by monitoring conductivity changes. The method is highly sensitive and allows measurements of IP3 in the pmolar range. Linearity was demonstrated over a wide range, 50-4500 pmol. The total imprecision was low with a coefficient of variation of 3%. When determining in biological tissue the recovery was estimated to be close to 100%. The mean content of IP3 in 15 rat heart specimens was 44.3 pmol/mg dry weight corresponding to tissue samples in the order of 4 mg wet weight. By noradrenaline stimulation myocardial content of IP3 increased by 50%.

Animals↗

Low energy charge in human uterine muscle.

Six pregnant and 10 non-pregnant patients undergoing Caesarean section and laparatomy, respectively participated in this study which was aimed at determining the energy status of human uterine muscle and comparing it to that of striated muscle from the same individual. Biopsies were taken from the fundus uteri between the ligamenta rotunda and from the rectus abdominis muscle. A low energy charge of 0.55 in pregnant patients and 0.64 in non-pregnant patients was observed in uterine biopsies, compared to the expected value of 0.90 found in rectus biopsies. The main determinant of this finding was a 4-8 times lower level of ATP in uterine biopsies compared to that in rectus biopsies. The same pattern was apparent for total nucleotide content and creatine phosphate. The ADP and AMP contents were of the same order of magnitude in both tissues. The lactate content in uterine biopsies from pregnant patients was significantly higher than that found in biopsies from rectus muscle and from uterine tissue of non-pregnant patients, indicating an increased glycogenolysis in pregnant uterus. The low energy charge and low level of phospho-compounds observed in uterine muscle, regardless of the functional state, are new and unexpected findings.

Abdominal Muscles↗

Increased whole blood viscosity combined with decreased erythrocyte fluidity in untreated patients with essential hypertension.

Erythrocyte fluidity and other haemorheological variables were studied in 22 patients with essential hypertension and compared with age- and sex-matched healthy controls. Hypertensive patients displayed a significantly lower erythrocyte fluidity (P less than 0.001). Similarly, significantly elevated values for haematocrit, plasma and whole blood viscosity, as well as aggregation tendency were observed compared to controls. Although differing in these respects from controls, there were no obvious relationships between these rheological variables and either systolic or diastolic blood pressure. The significantly lower erythrocyte fluidity and other changes in haemorheological variables of red blood cells found in hypertensive patients may be explained by an enlarged metabolic pool of free calcium ions in these red blood cells. It is suggested that the molecular mechanisms underlying the evolution of essential hypertension are multifactorial rather than being based on a single molecular derangement. Primary events resulting in altered physicochemical properties of the red blood cells may work in concert in the development of essential hypertension, in addition to the increased availability of calcium ions and their potential role in smooth muscle contraction.

Adult↗

Effects of alkaline buffer administration on survival and myocardial energy metabolism in pigs subjected to ventricular fibrillation and closed chest CPR.

Nineteen anaesthetized piglets were investigated. After characterization and a stabilization period, ventricular fibrillation was induced by a transthoracic DC shock, after which a 10-min period of cardiopulmonary resuscitation (CPR) took place. CPR included manual chest compression and mechanical ventilation with pure oxygen. After 1 min of CPR an infusion of alkaline buffer was begun and was completed within 5 min. A total of 50 mmol of one of two different buffer solutions was given, either sodium bicarbonate (n = 6) or tris buffer mixture (n = 7). These two groups were compared with a third control group (n = 6) receiving the same volume of normal saline. After 8 min of CPR all animals were given 0.5 mg adrenaline i.v., and after 10 min DC shocks were used to return the heart to normal sinus rhythm. If this procedure was successful, the heart was rapidly (within 15 s) stopped again by another DC shock. Myocardial biopsies were then taken immediately in all animals. Successful CPR was more frequent in the animals given normal saline or tris buffer mixture and no effect was seen in the group given sodium bicarbonate. Survival was statistically correlated to low myocardial content of creatine phosphate and low base excess values in blood. Such parameters as myocardial content of ATP or ACP (adenylate charge potential) had no direct correlation to survival. Sodium bicarbonate induced significantly higher base excess and PCO2 values, while the tris buffer mixture seemed to have a greater alkalizing effect intracellularly. We consider it probable that the poor results regarding survival after experimental CPR combined with a rapid infusion of sodium bicarbonate were a result of the excessive alkalosis created in combination with the higher resulting PCO2. Indirect evidence was given that a slightly alkaline pH also intracellularly supported critical reactions including ATPases essential for cellular survival.

Animals↗