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Biomedical subjects

B Persson

Publications and source records attributed to B Persson.

At least 271 records · Page 15Linked to original sources

Renal functional effects of prostaglandin synthesis inhibition in patients with insulin-dependent diabetes mellitus of long duration without nephropathy.

The short-term effects of prostaglandin synthesis inhibition (PGSI; single dose 500 mg of naproxen) on renal function were studied in six women (age: 21.9 +/- 2.4 yrs) with insulin dependent diabetes mellitus (IDDM) of 14.3 +/- 2.8 yrs' duration, and in nine age- and sex-matched controls. The diabetics had no overt signs of nephropathy (Albustix neg, normal serum creatinine, and blood pressure). The clearance of inulin (CIn) and PAH; the filtration fraction (FF); and the excretion of Na, albumin and PGE2 were studied under water diuresis on two separate mornings, first without and then with PGSI. With PGSI all individuals has lower PGE2 excretion. The CIn and FF were significantly (p less than 0.05) higher in the diabetics than in the controls both without (129.4 +/- 23.9 ml/min/1.73 m 2 and 23.4 +/- 2.8% vs. 107.6 +/- 10.3 and 19.7 +/- 1.6) and with (133.7 +/- 29.4 and 22.6 +/- 2.1, vs. 106.8 +/- 10.3 and 20.1 +/- 1.5) PGSI. The diuresis and Na excretion were significantly lower with PGSI, than without, in both groups. The albumin excretion was significantly higher in the diabetics under both conditions (29.9 +/- 16.6 and 34.2 +/- 19.9 micrograms/min/100 ml GFR, vs. 14.5 +/- 10.6 and 12.9 +/- 8.3 in controls). We conclude that the hyperfiltration in this stage of IDDM does not appear to be PG dependent, and that PGSI does not give any immediate effects on the albumin excretion.

Adult↗

Reflexogenic neuronal and humoral responses to selective stimulation of low-pressure cardiopulmonary receptors in man.

This study was conducted to determine the relative importance of efferent muscle sympathetic nerve activity (MSA), vasopressin (ADH) and atrial natriuretic peptide (ANP) in the short-term neurohumoral response to moderate changes in low-pressure cardiopulmonary receptor activity. The low-pressure receptors were stimulated and unloaded, respectively, by autotransfusion of blood (450 ml) and the application of lower body negative pressure (LBNP, -20 mmHg), and in 11 healthy men we measured MSA in the left peroneal nerve, indirect blood pressure, ECG, central venous pressure (CVP) and venous plasma concentrations of ANP and ADH (radioimmunoassay). Total MSA rose by 30% during LBNP and decreased during a rapid autotransfusion of blood, and the changes in MSA were significantly related to changes in CVP. The plasma concentrations of ADH and ANP were not significantly affected by either procedure. It is suggested that during moderate short-term changes in venous return, MSA responded more rapidly and/or at a lower threshold than the ADH and ANP systems.

Adult↗

Acute C-peptide, insulin and branched chain amino acid response to feeding in formula and breast fed infants.

The response of C-peptide in serum and urine and of glucose and branched chain amino acids in blood to formula and breast feeding was assessed in six breast-fed and six formula-fed infants 3-6 months of age. We analysed serum C-peptide, branched chain amino acids (BCAA) in blood, and blood glucose in the fasting state at 90' and 180' after a regular meal. The excretion of urinary C-peptide and creatinine was also determined. The formula-fed infants received a formula in current use, containing 15-16 g protein/l and with a casein/whey ratio of 40/60. In the fasting state, no significant inter-group difference was found in the level of serum C-peptide or the valine/glycine ratio. Postprandially, the formula-fed infants had significantly higher serum C-peptide values and valine/glycine ratio than the breast-fed infants, p less than 0.05. No significant inter-group difference was found for blood glucose. The urinary C-peptide/creatinine ratio was significantly lower in the breast-fed group, p = 0.02, and significantly correlated both to the valine/glycine ratio at 90', rs = 0.75, p = 0.02 and to the serum C-peptide value at 90', rs = 0.66, p = 0.03. These results confirm that in formula-fed infants the insulin response to a meal is enhanced compared to that in breast-fed infants. The finding of similar blood glucose values in the two groups may also indicate an insulin resistance in the formula-fed infants following a meal.

Amino Acids, Branched-Chain↗

Urinary C-peptide excretion in obese and anorectic children.

To assess the total insulin secretion in children in different nutritional states we have analysed the 24 h urinary C-peptide excretion in 32 obese children (16 boys and 16 girls) 8-15 years of age as well as in 7 girls with anorexia nervosa 11-16 years of age. Obese children had a median urinary C-peptide excretion rate of 0.27 nmol/kg/24 h, which was not different from that of a group of normal-weight children. In the group of anorectic girls, on the other hand, the median value 0.47 nmol/kg/24 h was significantly (p less than 0.05) higher than for normal-weight girls of the same age (median = 0.26 nmol/kg/24 h). These results indicate that in obese children insulin secretion, measured as the 24 h urinary C-peptide excretion per kg body weight, is the same as in normal-weight children. Total insulin secretion is consequently increased. In anorexia nervosa, on the other hand, the higher C-peptide excretion per kg body weight compared with normal-weight children, indicates that insulin secretion is increased in relation to body weight.

Adolescent↗

Clinical pharmacokinetics of ketanserin.

Ketanserin is a serotonin S2-receptor antagonist introduced for the treatment of arterial hypertension and vasospastic disorders. Plasma concentrations of ketanserin (and some metabolites) can be measured with high performance liquid chromatography using ultraviolet or fluorescence detection, or by radioimmunoassay. The methods are sensitive, accurate and specific. Following oral administration ketanserin is almost completely (more than 98%) and rapidly absorbed and peak concentrations in plasma are reached within 0.5 to 2 hours. It is subject to considerable extraction and metabolism in the liver (first-pass effect) and the absolute bioavailability is around 50%. The compound is extensively distributed to tissues and the volume of distribution is in the order of 3 to 6 L/kg. In plasma ketanserin binds avidly to plasma proteins, mainly albumin, and the free fraction is around 5%. Ketanserin is extensively metabolised and less than 2% is excreted as the parent compound. The major metabolic pathway is by ketone reduction leading to formation of ketanserin-ol which is mainly excreted in the urine. Ketanserin-ol, which by itself does not contribute to the overall pharmacological effect, is partly reoxidised into ketanserin, and it is likely that the terminal half-life of the parent compound is related to the slow ketanserin regeneration from the metabolite. Following intravenous administration plasma ketanserin concentrations decay triexponentially with sequential half-lives of 0.13, 2 and 14.3 h. The terminal half-life is similar after oral administration. Following long term oral dosing (20 or 40 mg twice daily) the pharmacokinetics remain linear and steady-state concentrations, which can be predicted from single-dose kinetics, are reached within 4 days. During long term treatment with the common dosage of 40 mg twice daily, steady-state concentrations fluctuate between 40 micrograms/L (trough) and 100 to 140 micrograms/L (peak). The pharmacokinetic properties of ketanserin are predictable in a wide group of patients and there is no influence from the duration of treatment, age and sex of the patient or concomitant treatment with beta-blockers or diuretics. There is no direct relationship between plasma concentrations of ketanserin and the antihypertensive effect in a group of patients. Side effects, including prolongation of the Q-T interval, are dose-dependent and, at least in the individual patient, related to peak plasma concentrations. In separate studies the pharmacokinetics of ketanserin were investigated in special patient groups, namely the elderly and patients with hepatic and renal insufficiency.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

Follow-up of women with previous GDM. Insulin, C-peptide, and proinsulin responses to oral glucose load.

Gestational diabetes mellitus (GDM) is a strong predictor of glucose intolerance later in life. Former GDM (n = 145) and control (n = 41) subjects were studied 3-4 yr after the index pregnancy. They were subjected to a 75-g oral glucose tolerance test (OGTT) with measurements of insulin, C-peptide, and proinsulin in the basal state and every 30 min for 180 min. In the former GDM group, 5 subjects (3.4%) had developed non-insulin-dependent diabetes mellitus (NIDDM), and 32 (22%) had developed impaired glucose tolerance (IGT; by World Health Organization criteria). In the control group, 2 (4%) had IGT. In the GDM group, IGT or NIDDM was significantly associated with obesity (body mass index [BMI] greater than or equal to 25 kg/m2) and earlier diagnosis of GDM during pregnancy (P less than 0.001). Nonobese (BMI less than 25 kg/m2) GDM subjects with normal glucose tolerance at follow-up had significantly higher mean glucose (P less than 0.01), insulin (P less than 0.05), and proinsulin (P less than 0.001) values during the OGTT than control subjects, whereas there was no significant difference in C-peptide values. A comparison between control subjects with normal OGTT and BMI less than 25 kg/m2 (n = 39) and GDM subjects (n = 39) selected to have a comparable area under the glucose curve, BMI, and age demonstrated no group differences in glucose, C-peptide, or insulin levels, whereas the proinsulin levels were significantly higher (P less than 0.001) during the glucose load. The molar ratio between proinsulin and insulin was also significantly higher among the former GDM subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A fragment of triosephosphate isomerase competes with the vasoactive intestinal polypeptide (VIP) for binding to the VIP receptor.

A 28-residue N-terminal fragment of triosephosphate isomerase, TIM(1-28), has been purified from porcine upper intestine. It competes with VIP for binding to the VIP receptor on rat liver plasma membranes with an IC50 value of 2.8 mM, about 1000 times higher than that for VIP binding to the membranes. Except for a single positional identity and the number of amino acid residues, the amino acid sequences of TIM(1-28) and VIP are unrelated as regards primary structure. However, the ability to bind to the same receptor site may indicate common three-dimensional structural properties.

Amino Acid Sequence↗

Indications that branched chain amino acids, in addition to glucagon, affect the glomerular filtration rate after a high protein diet in insulin-dependent diabetes.

Hormonal changes and whole blood free amino acid levels and their relation to renal function were measured in 12 insulin-dependent diabetic patients after two 10-day periods with a diet consisting of 10% and 20% respectively of the energy as protein. The patients were 15-21 years old and mean duration of diabetes was 12 (5-20) years. Glomerular filtration rate, renal plasma flow, and albumin excretion rate were measured together with plasma concentrations of glucagon, growth hormone, insulin-like growth factor 1 (IGF-1), somatostatin, serum insulin and free amino acids in blood. Glomerular filtration rate was 123 +/- 3 ml/min/1.73 m2 on high protein diet and 113 +/- 3 ml/min/1.73 m2 on low protein diet (p = 0.02). Renal plasma flow was unchanged. Glucagon, IGF-1, branch chained amino acids (BCAA), tyrosine, phenylalanine, lysine, and methionine were increased after the high protein diet. Growth hormone, somatostatin, insulin, and other amino acids remained unchanged. The increase in glomerular filtration rate was significantly correlated to the increase in glucagon, isoleucine, and valine (glucagon r = 0.71, p = 0.01, isoleucine r = 0.59, p = 0.04, valine r = 0.62, p = 0.03). In a multiple regression model the increase in glomerular filtration correlated most strongly to the increase in isoleucine, followed by valine and glucagon. Together these variables explained 88% of the total variance of the change in glomerular filtration rate (r2 = 0.88, p = 0.001). Albumin excretion rate was correlated to IGF-1 (r = 0.86, p less than 0.001) on the high protein diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Real-time biospecific interaction analysis using surface plasmon resonance and a sensor chip technology.

We report here the development and application of a biosensor-based technology that employs surface plasmon resonance for label-free studies of molecular interactions in real time. The sensor chip interface, comprising a thin layer of gold deposited on a glass support, is derivatized with a flexible hydrophilic polymer to facilitate the attachment of specific ligands to the surface and to increase the dynamic range for surface concentration measurements. The sensor can be used to measure surface concentrations down to 10 pg/mm2. Typical coefficients of variation are from two to five percent. We anticipate that the ability to monitor multi-molecular complexes as they form will greatly contribute to the understanding of biorecognition and the structural basis of molecular function.

Antibodies, Monoclonal↗

A simplified model for management of women with gestational diabetes at the primary care level.

A simplified model for management of women with gestational diabetes mellitus (GDM) that could be applied at the level of the primary antenatal care was evaluated. Two groups were compared: group I included 172 consecutive GDM subjects cared for at the hospital-based specialized antenatal clinic 1984-85. Group II included 149 consecutive GDM subjects cared for at the primary antenatal clinics 1985-86. Both groups were instructed in self-monitoring of blood glucose and were given dietary instructions. Insulin treatment was initiated if blood-glucose exceeded 9 mmol/l post-prandially three times a week. While women in group II mainly were cared for by midwives, following the routine antenatal program, women in group I were seen every two weeks by an obstetrician and non-stress tests were performed twice weekly from gestational week 35. There were no significant differences with respect to the number of women who required insulin treatment, rate of pregnancy complications or mode of delivery. There were two intrauterine deaths, one in each group, both were unrelated to GDM. There were no group differences regarding large-for-gestational-age infants, respiratory disturbances, neonatal hypoglycemia, hyperbilirubinemia or polycythemia. We conclude that an effective care of GDM-women can be achieved at the primary care level provided frequent self-monitoring of blood glucose is performed for early detection of insulin requiring diabetes.

Adult↗

The gene from the short arm of chromosome 3, at D3F15S2, frequently deleted in renal cell carcinoma, encodes acylpeptide hydrolase.

Loss or inactivation of a gene on the short arm of chromosome 3 may contribute to the genesis of renal cell carcinoma. A gene that corresponds to the most frequently lost RFLP site (D3F15S2) is expressed in a variety of human tissues, and at a particularly high level in the kidney. Its expression is markedly reduced in renal cell carcinoma. A database search showed that the gene product is closely related to or identical with acylpeptide hydrolase. The nucleotide identity between the rat acylpeptide hydrolase and the human gene at D3F15S2 is 88%, compatible with normal species differences. It is therefore likely that the human gene product is acylpeptide hydrolase. The renal cell carcinoma is then associated with a decrease of acylpeptide hydrolase activity. The gene may represent a tumor suppressor gene, whose loss contributes to the development of renal cell carcinoma. It might be speculated that it could act e.g. by affecting the activity of a small acetylated growth factor. Alternatively, its decreased expression may merely reflect the impairment of differentiation in RCC, compared to normal kidney. Loss of a linked but irrelevant gene by the 3p deletion is another possibility.

Aminopeptidases↗

Fast atom bombardment mass spectrometry and chemical analysis in determinations of acyl-blocked protein structures.

Peptide generation and fast atom bombardment mass spectrometry in combination with conventional chemical analysis was used to identify the blocking group and establish the N-terminal structure of six different proteins at the nanomole level. In this manner, the first terminal structures of three non-mammalian alcohol dehydrogenases were determined, demonstrating the presence of N-terminal acetylation in these piscine, amphibian, and avian enzymes. Similarly, two different yeast glucose-6-phosphate dehydrogenases and a minor variant of a human alcohol dehydrogenase were found to be acetylated. The exact end location of C-terminal structures was also established. Together, the analyses permit the definition of terminal regions and blocking groups, thus facilitating the delineation of remaining structures.

Acetylation↗

Relationship between haemoglobin A1C in early type 1 (insulin-dependent) diabetic pregnancy and the occurrence of spontaneous abortion and fetal malformation in Sweden.

This prospective nationwide study examined the relationship between diabetic control in early pregnancy as assessed by HbA1C and the incidence of spontaneous abortion and fetal malformation. HbA1C and plasma C-peptide were determined in 532 women with Type 1 (insulin-dependent) diabetes mellitus, corresponding to approximately 80% of all the diabetic pregnancies in the country during the study period 1982-1985, and 222 non-diabetic control women. Median gestational week for sampling was 9.0 in the Type 1 diabetic and 10.0 in the control group. The median value of HbA1C was 7.7% in the diabetic and 5.3% in the control group (p less than 0.001). The rates of spontaneous abortion, 7.7% vs 7.2%, and malformation, 4.3% (major 2.0%) and 2.4% (major 1.0%), were not significantly different between the diabetic and control group, respectively. These rates of malformation were not significantly different from the national figures of 4.55% (major 1.75%). Much elevated HbA1C, i.e., greater than 10.1% equal to 8 SD above the normal mean control value, was significantly associated with the occurrence of spontaneous abortion (p less than 0.001) and malformation (p less than 0.01). Discriminant analysis revealed that after correction had been made for the significant value of HbA1C to predict the occurrence of spontaneous abortion and malformation, no further predictive power was displayed by measurable plasma C-peptide, maternal age or duration of diabetes or presence of diabetic microangiopathy. We conclude that poor metabolic control in early pregnancy contributes to an increased risk of both spontaneous abortion and fetal malformation.

Abortion, Spontaneous↗