Biomedical subjects

K Brismar

Publications and source records attributed to K Brismar.

97 records · Page 6Linked to original sources

PubMedDate not supplied

Effects of bromocriptine on CSF proteins and amines in patients with empty sella syndrome, acromegaly and prolactin producing pituitary adenomas.

The effect of the dopamine agonist bromocriptine (5-40 mg/day) on cerebrospinal fluid proteins and amines was studied in 7 hyperprolactinemic patients, 4 with empty sella syndrome and 3 patients with pituitary adenoma. Small as well as high doses of bromocriptine depressed the endogenously formed dopamine, noradrenalin and adrenalin. Five patients initially exhibited changes consistent with slight to marked blood-cerebrospinal-fluid (CSF) barrier disturbances and 5 abnormal CSF-protein fractions. One CSF-protein fraction (isolelectric points (pI) approximately 5.3 pH-units) became more prominent during bromocriptine treatment. Analyses of his fraction indicated that it represented a transferrin component. It is stated that bromocriptine treatment besides affecting amine and trace metal metabolism also affects protein metabolism.

Acromegaly↗

PubMedDate not supplied

Growth hormone secretion in empty sella syndrome.

GH secretion was studied in 47 patients with empty sella syndrome (ESS), using the GH response to the L-dopa test and determinations of the somatomedin levels. A high frequency of low responders (56%) was found, which is in accordance with previous reports on ESS. However, a true GH deficiency as judged by low levels of somatomedin A, was suspected in only 2 out of 41 patients with otherwise normal pituitary function and in 5 out of 6 patients with other pituitary insufficiences. The impaired GH responsiveness in the remaining patients seemed to be attributed to their overweight and/or postmenopausal age (estrogen deficiency) and not to a true GH deficiency, which was excluded by normal levels of somatomedin.

Adolescent↗

PubMedDate not supplied

Short-term hypocaloric nutrition but not bed rest decrease insulin sensitivity and IGF-I bioavailability in healthy subjects: the importance of glucagon.

Hyperinsulinemic, normoglycemic clamps were performed before and after 24 h of either hypocaloric nutrition or bed rest in healthy subjects. Decreased insulin sensitivity and insulin-like growth factor-I (IGF-I) bioavalibility, as measured by the serum IGF-I/insulin-like growth factor binding protein-1 (IGFBP-1) ratio, was found after fasting, whereas no metabolic changes were found after bed rest. Glucagon seems to be a key regulator of IGFBP-1 after brief hypocaloric nutrition. Hypocaloric nutrition and immobilization may add to the catabolic response to surgery and other trauma. Presently, six healthy subjects were studied before and after a 24-h period of hypocaloric nutrition (200 kcal/24 h, fast) or immobilization (bed rest) using the hyperinsulinemic (0.8 mU.kg-1.min-1), normoglycemic (4.5 mmol/L) clamp, indirect calorimetry, and circulating levels of substrates and hormones. After fast, body weight decreased (P < 0.05), and nitrogen balance was negative (-10 +/- 1 g urea nitrogen/24 h). Basal levels of free fatty acids, glucagon, and IGFBP-1 increased (P < 0.05), whereas c-peptide levels and the IGF-I/IGFBP-1 ratio decreased (P < 0.05). However, no change was found in basal levels of IGF-1 or substrate oxidation. Furthermore, changes (%) in basal levels of glucagon after fast correlated to IGFBP-1 (r = 1.0, P < 0.05), whereas the suppressibility of IGFBP-1 by insulin was maintained at normal levels. During clamps, glucose infusion rates (GIR) decreased after fast (-43 +/- 13%, mean +/- SEM, P < 0.001). Although not significantly, clamp levels of fat oxidation tended to increase and glucose oxidation tended to decrease. Levels of IGFBP-1 during clamps were higher as compared with the control clamp (P < 0.05). No adverse metabolic changes were seen after bed rest, and no change in GIR during clamps were seen as compared with the control measurement (0 +/- 14%). After brief hypocaloric nutrition, insulin sensitivity is reduced, whereas IGF-I bioavalibility is reduced by an increase in levels of IGFBP-1. Glucagon seems to contribute to the increase in IGFBP-1 during these conditions.

Adult↗

PubMedDate not supplied

Decreased cortical bone thickness in spontaneously non-insulin-dependent diabetic GK rats.

We studied the occurrence of osteopenia, as reflected by decreased cortical bone thickness, in a nonobese animal model of hereditary non-insulin-dependent diabetes with long duration, i.e., 8-month-old Goto-Kakizaki (GK) rats. In addition, motor nerve-conduction velocity was measured in the GK rats. Age- and weight-matched Wistar rats served as controls. The GK rats displayed marked glucose intolerance, as compared to control rats, in an intraperitoneal glucose tolerance test. Decreased cortical bone thickness by approximately 15%, was evident in X-ray analysis of metatarsal bones (p < 0.001) and humerus (p < 0.05) of the GK rats. Motor nerve-conduction velocity, measured in the sciatic nerve, was also decreased (by 10%) in the GK as compared with the age-matched control rats (p < 0.05). In conclusion, reduction of cortical bone thickness is present in 8-month-old GK rats, which simultaneously demonstrate signs of peripheral neuropathy. Thus, the GK rat appears to be a model of NIDDM suitable for studies of diabetic bone disease in the absence of obesity.

Animals↗

PubMedDate not supplied

Dose-dependent hyperbaric oxygen stimulation of human fibroblast proliferation.

Diabetic wounds are characterized by a prolonged wound healing process with insufficient formation of granulation tissue. Systemic hyperbaric oxygen therapy has been observed to improve the healing of these wounds. However, the mechanism(s) responsible for these findings are not yet fully elucidated. In the present study we have studied the in vitro effects of hyperbaric oxygen on proliferation of human fibroblasts from normal skin and from chronic foot ulcers in non-insulin-dependent diabetics. A 1-hour exposure to hyperbaric oxygen at oxygen pressures between 106 and 300 kPa (795 to 2250 mm Hg) increased the proliferation in both diabetic and normal fibroblasts. The stimulatory effect was dose-dependent, with a peak increase in cell proliferation at 250 kPa and 200 kPa for normal and diabetic cells, respectively. The effects were not due to hydrostatic pressure per se. These results suggest that hyperbaric oxygen could stimulate fibroblast activity in the diabetic wound, a finding that could explain the enhanced formation of granulation tissue seen clinically in wounds treated with hyperbaric oxygen. We also speculate that mechanisms other than just increased oxygen availability may be responsible for our findings.

Journal Article↗

PubMedDate not supplied

Inhibited proliferation of fibroblasts derived from chronic diabetic wounds and normal dermal fibroblasts treated with high glucose is associated with increased formation of l-lactate.

Diabetes is accompanied by delayed wound healing and insufficient granulation tissue formation, possibly because of a defect in fibroblast function. We have previously shown that fibroblasts derived from chronic diabetic foot ulcers have lower proliferation compared with those from uninjured skin. The aim of this study was to investigate possible mechanisms explaining the impaired fibroblast proliferation observed in fibroblasts from non-insulin-dependent diabetes mellitus chronic wounds and normal fibroblasts cultured in high glucose. Fibroblasts from two groups of patients were studied: nondiabetic patients with chronic venous stasis ulcers and non-insulin-dependent diabetes mellitus patients with chronic diabetic wounds. Biopsies from both uninjured skin and wounds were taken from the same patients to serve as sources of fibroblasts. A fluorometric method was used to determine DNA content, and a spectrophotometric lactate oxidase method was used for lactate level analysis. We found a dose-dependent inhibition of normal fibroblast proliferation when adding conditioned media from non-insulin-dependent diabetes mellitus wound fibroblasts. The conditioned medium, from these cells showed elevated l-lactate levels, 6.3 +/- 0.7 mmol/L, compared with media derived from nondiabetic, 2.1 +/- 0.3 mmol/L (p < 0.01), and diabetic uninjured skin fibroblasts, 3.5 +/- 0.6 mmol/L, and from chronic nondiabetic wound fibroblasts 2.9 +/- 0.3 mmol/L. Addition of 6 mmol/L l-lactate to uninjured normal fibroblasts resulted in decreased DNA content (58 +/- 7%, p < 0.01). Previously we have shown that high glucose concentrations inhibit fibroblast proliferation and induce growth factor resistance. When increasing the amount of d-glucose in the media, l-lactate levels increased in all cell types. When the uninjured normal cells were treated with beta-hydroxybutyrate, the total DNA content decreased by 42 +/- 5% (p < 0.05), with no significant increase in the l-lactate levels. These observations indicate that l-lactate production may be of importance for fibroblast proliferation in vitro and may play a role in fibroblast proliferation in vivo.

3-Hydroxybutyric Acid↗

PubMedDate not supplied

Impaired proliferation and increased L-lactate production of dermal fibroblasts in the GK-rat, a spontaneous model of non-insulin dependent diabetes mellitus.

Intact fibroblast function is required for normal wound healing. Although healing is generally accepted to be disturbed in non-insulin dependent diabetes mellitus, the signals modulating this disturbance are not fully understood. Therefore, we studied dermal fibroblasts from the GK rat, a non-insulin dependent diabetes mellitus model, and the Wistar rat (control) regarding growth characteristics, and L-lactate production at 5.5 mM and 25.5 mM glucose in the absence or presence of protein kinase C-inhibition, or alpha-tocopherol acetate. In addition, growth and L-lactate responses to hyaluronic acid were assessed under normal glucose conditions. At 5.5 mM glucose, the fibroblasts from the GK rat showed a lower proliferation rate during the first 24 hours, measured as DNA content, as compared to Wistar rats, i.e. at 8 hours GK was 57% of control, p < 0.01, at 24 hours GK was 60% of control, p < 0.01. The GK rat fibroblasts accumulated higher L-lactate levels in the media at 24-96 hours. Addition of glucose at a concentration of 25.5 mM decreased the total DNA content in GK rat fibroblast cultures to 74% (p < 0.05) and in control to 87% (p < 0.05), and increased L-lactate levels, measured at 48 hours. A protein kinase C-inhibitor, bisindolylmaleimide IX, increased DNA content and decreased L-lactate in both cell types during culture in high glucose, but only affected GK rat fibroblasts during normal glucose. Hyaluronic acid, increased DNA content in both types of fibroblasts, GK: 139% (p < 0.05), control: 127% (p < 0.05) and reduced L-lactate production. The above observations indicate that GK rat fibroblast proliferation is suppressed when the cells are cultured in high glucose containing media. In addition, protein kinase C and hyaluronic acid might play a role as modulators of fibroblast proliferation during the diabetic state.

Adjuvants, Immunologic↗