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Biomedical subjects

P Pietschmann

Publications and source records attributed to P Pietschmann.

At least 55 records · Page 3Linked to original sources

Interaction of triiodothyronine with 1alpha,25-dihydroxyvitamin D3 on interleukin-6-dependent osteoclast-like cell formation in mouse bone marrow cell cultures.

In mouse bone marrow cultures, the formation of osteoclast-like, that is, tartrate-resistant acid phosphatase-positive (TRAP+) and calcitonin (CT) receptor-positive multinucleated cells (MNCs), induced by 10(-10) to 10(-8) mol/L 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3], could be augmented by triiodothyronine (T3), which alone had no effect on osteoclast-like cell formation. The permissive effect of T3 increased the response to 1alpha,25(OH)2D3 by approximately one order of magnitude. Linear concentration dependence was observed between 10(-11) and 10(-8) mol/L T3. Importantly, inhibition of prostaglandin synthesis by indomethacin significantly impeded osteoclast-like cell formation by 1alpha,25(OH)2D3 and abrogated the effect of T3 thereon. Basal interleukin-6 (IL-6) production by cultured marrow cells was significantly stimulated by 1alpha,25(OH)2D3. However, even at an exceedingly high concentration of 20 ng/mL, IL-6 was ineffective in inducing osteoclast-like cell formation. Therefore, any hormonally induced rise in IL-6 release from bone marrow cells could not account for the observed changes in TRAP+ MNC numbers. Nevertheless, the stimulatory effect of 1alpha,25(OH)2D3 on osteoclastogenesis was partially dependent on IL-6 because it could be significantly blocked by a neutralizing monoclonal anti-IL-6 antibody, and to the same extent by a monoclonal anti-IL-6 receptor antibody. Unimpaired signaling through the IL-6/IL-6R system is also a prerequisite for the auxiliary effect of T3 on induction of osteoclast-like cells by 1alpha,25(OH)2D3. Our data provide evidence that 1alpha,25(OH)2D3 induces osteoclast-like cell formation, at least in part, in an IL-6-dependent mode of action, which is also subject to modulation by T3. The mechanism of interaction of the two hormones apparently involves joint stimulation of prostaglandin synthesis.

Acid Phosphatase↗

High turnover bone disease following lung transplantation.

Recipients of lung transplants are at very high risk for significant bone loss. Nevertheless, data on bone disease after lung transplantation are still limited. We, therefore, retrospectively evaluated the data of 33 patients surviving at least 1 year after lung transplantation (LTx) who were seen in our outpatient clinic for osteologic evaluation. Results of clinical evaluations, radiographs, and dual-energy X-ray absorptiometry (DXA) were related to each other, to clinical variables, and to serum levels of osteocalcin, parathyroid hormone (PTH), and 25-hydroxyvitamin D: 14 of 33 patients (42%) had vertebral fractures, 9 of whom were diagnosed within 2 years after transplantation. Bone mineral density values (DXA) were markedly decreased and predictive of compression fractures. 25-Hydroxyvitamin D levels were low in 13 patients (39%) and PTH was elevated in 7 (21%). Despite corticosteroids and low 25-hydroxyvitamin D, serum osteocalcin was elevated in 12 patients (36%). This was only partially explained by hyperparathyroidism, low sex hormones, and impaired renal function, and may partly be caused by cyclosporin A. We thus conclude that severe symptomatic bone disease is common in lung transplant recipients and due to a complex situation including high turnover bone loss and hypovitaminosis D. DXA can be used to estimate fracture risk for individual patients.

Absorptiometry, Photon↗

Immunophenotypic characteristics of monocytes in elderly subjects.

Since ageing is accompanied by various alterations of the immune system, the aim of the present study was to investigate the effect of age on the expression of surface markers in peripheral blood monocytes. We studied 28 healthy young subjects and 28 elderly subjects fulfilling the criteria of the SENIEUR protocol. Peripheral blood mononuclear cells were isolated and the expression of various surface markers was analysed by double colour flow cytometry. The mean fluorescence intensity of the intercellular adhesion molecule- (CD54), CD29, CD45RO and CD32 was increased significantly in CD14+ cells of elderly people when compared with the young subjects. No significant differences were found in the expression of CD11a, CD11b, CD15, CD26, CD27, CD33, CD45RA, CD45RB, CD49d, HLA-DR and CD65. In summary, we demonstrated significant increase in four monocyte surface markers in subjects of old age; this finding may be related to certain immune phenomena observed in ageing subjects such as auto-immunity.

Adult↗

Salmon calcitonin and calcium in the treatment of male osteoporosis: the effect on bone mineral density.

OBJECTIVE: To assess the effectiveness of salmon calcitonin in the therapy of male osteoporosis. METHODS: Nine male patients aged 20-73 years with vertebral osteoporosis were included in this study. Patients were prescribed 100 units of salmon calcitonin injected subcutaneously three times per week over a period of three months, followed by three months without salmon calcitonin treatment. Thereafter the patients received another salmon calcitonin cycle for three months as described above. All men received calcium supplementation of 1000 mg/day throughout the study period of 12 months. Bone mineral density of the lumbar spine and at the hip was measured at the beginning and the end of the treatment period using DXA (n = 7) or QCT (n = 2). RESULTS: Baseline evaluation revealed a bone mineral density of the lumbar spine of 0.78 +/- 0.09 g/cm2 and 0.62 +/- 0.09 g/cm2 at the hip. Treatment with salmon calcitonin resulted in a significant increase of vertebral bone mineral density to 0.80 +/- 0.09 g/cm2 (p < 0.015). Femoral bone mineral density also significantly increased after salmon calcitonin therapy to 0.64 +/- 0.11 g/cm2 (p < 0.05). CONCLUSION: These results show that calcium and salmon calcitonin increase bone mineral density in male patients with osteoporosis. Calcium and calcitonin may be useful in the treatment of male osteoporosis; however, further studies are necessary before definite recommendations can be made.

Adult↗

Comparative study on the effect of calcium channel blockers on basal and parathyroid hormone-induced bone resorption in vitro.

A number of clinical and experimental studies suggest that the effects of calcium channel blockers are not limited to the cardiovascular system but might also involve skeletal calcium metabolism due to the presence of L-type calcium channels in osteoblastic cells. We therefore investigated the influence of calcium channel blockers of the dihydropyridine type (nifedipine, amlodipine) as well as of the phenylalkylamine type (verapamil, gallopamil) on basal and parathyroid hormone-induced bone resorption utilizing organ-cultured neonatal mouse calvaria. Only at 10(-4) M, amlodipine, verapamil and gallopamil reduced basal and parathyroid hormone-induced resorption In contrast, nifedipine, between 10(-5)-10(-4) M, exhibited a dose-dependent inhibitory effect on parathyroid hormone-related bone resorption by up to 50%. When calvariae were cultured for 48 hr in the presence of inhibitory concentrations of the calcium channel blockers and then stimulated with parathyroid hormone, only parietal bones pretreated with nifedipine remained completely responsive to the bone resorbing action of the hormone.

Amlodipine↗

17Beta-estradiol antagonizes effects of 1alpha,25-dihydroxyvitamin D3 on interleukin-6 production and osteoclast-like cell formation in mouse bone marrow primary cultures.

In mouse bone marrow primary cultures, the formation of osteoclast-like, i.e. tartrate-resistant acid phosphatase (TRAP)- and calcitonin receptor-positive multinucleated cells (MNC), when induced by 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3), can be suppressed by 17beta-estradiol (17beta-E2), whereas 17alpha-E2 is without any effect. 17beta-E2, above 10(-11) M, significantly reduced 1alpha,25(OH)2D3-mediated TRAP+ MNC formation in cultured bone marrow cells from both female and male mice. The estrogen at 10(-8) M suppressed the peak response to the vitamin D sterol by 50%. 17beta-E2 significantly suppressed basal and 1alpha,25(OH)2D3-stimulated cellular production of interleukin (IL)-6. IL-6 alone, although bone marrow cells in hormone-free culture produced appreciable amounts of the cytokine, did not induce any TRAP+ MNC. Therefore, the changes in IL-6 production induced by the hormones could not be the sole determinant for the extent of TRAP+ MNC formation. However, the stimulatory effect of 1alpha,25(OH)2D3 on osteoclastogenesis nevertheless can be significantly reduced by a neutralizing monoclonal anti-IL-6 antibody. In the presence of 10(-8) M 17beta-E2, the anti-IL-6 monoclonal antibody does not achieve any further suppression of 1alpha,25(OH)2D3-related osteoclast-like cell formation. Our data suggest that induction of osteoclastogenesis by 1alpha,25(OH)2D3 is partially dependent on IL-6 signaling and can be modulated by 17beta-E2 through interference with IL-6 receptor activation, in addition to inhibition of IL-6 production by marrow stromal cells.

Acid Phosphatase↗

[Clinical aspects and diagnosis of uric acid arthritis].

Gout is an acute or chronic crystal induced arthritis which develops secondary to hyperuricemia. In this review the clinical features and the diagnosis (physical examination, laboratory investigations, radiology) of gout are discussed.

Arthritis, Gouty↗

The effect of age on the transendothelial migration of human T lymphocytes.

Since the migration of immunologically active cells into perivascular tissue is an important step in acute and chronic inflammation, the authors studied the possible influence of age on the transendothelial migration of T cells in an in vitro model. After incubation on collagen gels coated with human endothelial cells, three populations of T cells of elderly and young subjects were harvested: non-adherent (NAD), bound (BND) and migrated (MIG) cells. The percentages of the BND and MIG fractions were similar in the young and elderly groups. Phenotypic analysis showed that in the starting population of the elderly subjects T-cell subpopulations that have an increased capacity of transendothelial migration (e.g., CD4+ memory cells, CD8+/CD57+ cells) were enriched: nevertheless ageing was not associated with an increase in the transendothelial migration of T cells.

Adult↗

Enhanced serum levels of thiobarbituric-acid-reactive substances in diabetes mellitus.

PURPOSE: To investigate whether serum levels of lipid peroxides measured as thiobarbituric-acid-reactive substances (TBARS) differ in type I and type II diabetic patients, whether serum levels correlate with late sequelae of diabetes, and whether serum levels of free vitamin E correlate with levels of lipid peroxidation by-products. PATIENTS AND METHODS: The relationship among lipids, glycosylated hemoglobin A1c (HbA1c), lipid peroxides measured as TBARS, and free vitamin E was determined in 158 patients. Fifteen of the 77 patients with type I diabetes and 39 of the 81 patients with type II diabetes had clinically apparent peripheral vascular disease or coronary artery disease, or both. RESULTS: Compared with control subjects, serum levels of TBARS were found to be significantly elevated (P < 0.001) in diabetic patients, and type II diabetic patients had significantly higher levels (P < 0.001) than type I patients. Both type I and type II diabetic patients with good metabolic control (HbA1c < 6.5%) had significantly lower (P < 0.005) TBARS levels than patients with poor metabolic control, but all groups had higher levels than the control group. Type II patients with angiopathy had significantly higher levels of TBARS than patients without angiopathy. Free vitamin E levels in control subjects and diabetic patients did not differ statistically. CONCLUSION: Serum levels of TBARS were significantly increased in all patients suffering from diabetes mellitus, whereby TBARS levels did not depend on the total amount of circulating lipids. It can be suggested that the enhanced lipidperoxidation is contributed to an increased formation of free radicals in diabetes mellitus.

Adult↗

Differential expression of various T cell surface markers in young and elderly subjects.

The purpose of this study was to investigate the expression of lymphocyte markers in the peripheral blood of aged individuals and of young healthy blood donors. Results showed significant changes in the distribution of various T cell subpopulations. The CD3, CD4 and CD8 surface expression was not different in the elderly patients when compared to the young subjects. The number of CD4+ T cells expressing CD45 RO isoform (memory cells) was increased in aged people; CD45 RA+ CD4+ cells (naive cells) were decreased. The expression of the CD45 RB on the CD4+ cells was significantly lower in the elderly when compared to the young subjects. In contrast, the surface expression of CD45 RO and CD45 RB in the CD8+ cells was not statistically different in the young and aged subjects. The proportion of CD8+ cells coexpressing CD57 was significantly increased in the elderly subjects. These results indicate age-dependent alterations of various surface markers of T cells. These observations may be of importance in the investigation of immunoregulatory mechanisms in geriatric patients with infection, autoimmune disease or cancer.

Adult↗

A program to reduce onset distress in unselected type I diabetic patients: effects on psychological variables and metabolic control.

This paper reports the results of a prospective controlled trial of a program addressing reduction of onset distress and better future adaptation in adults who were enrolled at the time of diagnosis of type I diabetes mellitus. Patients were assigned randomly to either standard intensive treatment and patient education with the distress reduction program (N = 10) or to standard intensive treatment and patient education without this program (N = 13). Prospective follow-up of patients with multiple validated measures of treatment outcome showed less anxious coping behavior, less depression and less denial at the 9-month follow-up and less denial at the 15-month follow-up in the group with the distress reduction program, but no differences in metabolic control between the two groups at any time. We conclude that our program has a positive impact on the crisis at diabetes onset; the lower denial in the treatment group may lead to improved regimen adherence in the long term.

Adaptation, Psychological↗

Comparison of serum fluoride levels after administration of monofluorophosphate-calcium carbonate or sodium fluoride: differences in peak serum concentrations.

Fluoride salts are widely used in Europe in the treatment of established osteoporosis with crush fractures for their ability to increase trabecular bone mass. However, in the United States fluorides are still regarded as an experimental drug. In a prospective, randomized study we compared the fluoride pharmacokinetics of enteric-coated sodium fluoride and disodium monofluorophosphate calcium carbonate (MFP-Ca) over the period of 76 h. Twenty subjects (12 females, 8 males), aged 35-80 years, free of gastrointestinal disorders, renal impairment, and liver disease and without prior fluoride intake entered the study. Ten subjects received NaF (11.3 mg fluoride) twice a day and the other ten MFP-Ca (13.2 mg fluoride) twice a day. During the study period of 76 h the patient's usual food intake was not changed. Serum fluoride levels were determined using an ion sensitive electrode. After intake of a single drug preparation of MFP-Ca or NaF, MFP-Ca showed a significantly shorter lag time of absorption and a significantly higher maximal serum fluoride concentration than NaF (P < 0.01). A comparison of fluoride cumulative characteristics of both drugs showed virtually identical serum fluoride levels before intake of the morning dose on all 4 study days, whereas serum fluoride concentrations measured 4 h afterwards were significantly higher for MFP-Ca than for NaF. These data provide evidence of high "peak" serum fluoride levels for MFP-Ca, whereas only small peak-to-trough fluctuations are seen for NaF.

Adult↗

Psychological moderator variables and metabolic control in recent onset type 1 diabetic patients--a two year longitudinal study.

The relationships between psychosocial adjustment and subsequent glycaemic control were prospectively examined in forty-three adult patients during the first 2 yr after onset of type 1 diabetes mellitus. Decreasing depression was the single psychosocial parameter that changed over time. No correlations were found between the decrease in HbA1c levels and psychological variables at 8- and 16-month follow-ups. Global and specific coping features such as high control attitude, low coping anxiety and low emotional attribution correlated significantly with the decrease in HbA1c levels at the 2-yr follow-up, whereas stressful life events, depression, state-trait anxiety did not correlate. In a regression analysis coping explained 22% variance of the 2 yr decrease in HbA1c levels. We conclude that coping is a better predictor for metabolic control than emotional adaptation and life events. Metabolic control might deteriorate with prolonged stage of the disease being a first sign for psychophysiological coping exhaustion.

Adaptation, Psychological↗

Apolipoprotein (a) levels and atherogenic lipid fractions in relation to the degree of urinary albumin excretion in type 2 diabetes mellitus.

The relationship between serum lipids, apolipoprotein levels including apolipoprotein (a) to albumin excretion rate (AER) in 52 (17 male, 35 female) type 2 diabetic patients was studied. Patients were classified in groups as follows: (1) patients with normal AER (< 30 mg/24 h); (2) patients with microalbuminuria (AER 30-300 mg/24 h), and (3) patients with macroalbuminuria (AER > 300 mg/24 h). Apolipoprotein B levels were significantly (p < 0.05) elevated in the patients with macroalbuminuria compared to the normoalbuminuric group. Further, we observed a significant correlation between total cholesterol, low-density lipoprotein cholesterol, as well as apolipoprotein B levels to the degree of AER. No correlation between apolipoprotein (a) levels and AER, which is in contrast to recently published data for type 1 diabetic patients, was found. Systolic blood pressure was significantly higher (p < 0.002) in the patients with micro- and macroalbuminuria compared to the group with normal albumin excretion, whereas no relationship between diastolic blood pressure and albuminuria was found. We conclude that elevated increased atherogenic lipid fractions in addition to systolic hypertension may contribute to an increased cardiovascular risk in type 2 diabetic patients with proteinuria.

Aged↗

Influence of sex and age on biochemical bone metabolism parameters.

Age-related changes in bone metabolism are of interest in the pathogenesis of postmenopausal and senile osteoporosis; however, data in the literature give conflicting results. Thus, the aim of our study was to measure serum levels of osteocalcin, a specific biochemical parameter of bone formation, as well as serum levels of midregional parathyroid hormone (PTH) and alkaline phosphatase in healthy males and females of various age groups. We studied 155 healthy subjects (91 females, 64 males, mean age: 43 years, age range: 20-81 years). Serum levels of osteocalcin, alkaline phosphatase and PTH increased with age and were significantly higher in the postmenopausal than in the premenopausal females (osteocalcin: 8.7 +/- 0.4 vs. 6.5 +/- 0.3 ng/ml, p < 0.0001; alkaline phosphatase: 126 +/- 7 vs. 89 +/- 5 U/l, p < 0.0003; PTH: 111 +/- 10 vs. 61 +/- 9 pmol/l, p < 0.0001). In contrast, serum levels of osteocalcin, alkaline phosphatase and PTH were similar in the male subjects above or below the age of 50 years (osteocalcin: 6.5 +/- 0.5 vs. 7.2 +/- 0.4 ng/ml, non significant; alkaline phosphatase: 104 +/- 8 vs. 105 +/- 5 U/l, non significant; PTH: 59.6 +/- 6 vs. 61 +/- 5 pmol/l, non significant. Serum calcitonin levels were significantly lower in postmenopausal women and men above 50 years of age. Our data suggest different age-related alterations in bone metabolism in males and females. The increased levels of osteocalcin, alkaline phosphatase and PTH in postmenopausal females give evidence of increased bone turnover in these subjects. In healthy men bone-specific markers remained unchanged, indicating no relationship between bone turnover and age.

Adult↗

Apolipoprotein (a) levels in patients with type 1 diabetes mellitus are unrelated to metabolic control or vascular disease.

Increased serum levels of lipoprotein (a) have been found to be an independent risk factor for coronary heart disease. The major protein constituents of lipoprotein (a) are apolipoprotein B 100 und apolipoprotein (a) (apo(a)). We determined the serum levels of apo(a) and several lipid (cholesterol, HDL- and LDL-cholesterol, triglycerides, apolipoproteins A, A1 and B) and glycaemic (HbA1c, fasting blood glucose) parameters in 40 patients with type 1 diabetes mellitus and in 103 age- and sex-matched control subjects. The median serum levels of apo(a) were significantly increased in the type 1 diabetic patients (142.7 vs. 80.0 U/L; P = 0.03), whilst HDL, LDL-cholesterol, and apolipoprotein A, A1 and B levels were lower (P < 0.01). No significant correlation was found between parameters of metabolic control and apo(a) levels. After subdivision of the diabetic patients according to different stages of diabetic nephropathy (DN), determined by urinary albumin excretion, significant relationships were found between DN and triglycerides (P = 0.04), LDL (P = 0.03) and apolipoprotein B (P = 0.008, Kruskal-Wallis test) levels. Apo(a) levels were significantly higher than normal values in patients without DN (P < 0.05), but unrelated to the degree of DN. Patients with diabetic macroangiopathy had significant higher levels of cholesterol (P = 0.0001), triglycerides (P = 0.026), LDL (P = 0.0003), and apoB (P = 0.002) than patients without. Apo(a) levels were unrelated to diabetic macroangiopathy. The significantly elevated levels of apo(a) even in patients without DN or macroangiopathy are noteworthy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Haemostatic abnormalities persist despite glycaemic improvement by insulin therapy in lean type 2 diabetic patients.

Diabetes mellitus is associated with disturbances of the hemostatic system, which might contribute to the development of diabetic vascular disease. We investigated the effect of metabolic improvement by insulin therapy on the haemostatic system in 61 patients with type 2 diabetes mellitus and secondary sulfonylurea failure compared with 45 healthy control subjects matched for age, sex and BMI. Median age was 65, median diabetes duration 10 years. Median HbA1c (10%) and fructosamine (4.0 mM) levels were elevated before induction of therapy and decreased significantly within 6 months of insulin treatment to 7.5% and 3.0 mM, respectively (p < 0.0001). Compared with control subjects, median plasma levels of fibrinogen (317 vs 286 mg/dl), coagulation factor VII activity (1.1 vs 0.89 U/l), von Willebrand factor (1.6 vs 1.3 U/l), D-dimer (105 vs 86 micrograms/l), protein C:Ag (1.24 vs 0.95 U/l), total protein S:Ag (1.15 vs 0.91 U/l), and antithrombin III activity (1.17 vs 1.08 U/l) were significantly elevated. Levels of free protein S were not different from control values. No significant decline of coagulation parameters could be recorded during insulin therapy. Patients with diabetic vasculopathy had higher levels of D-dimer than those without (133 vs 76 micrograms/l before, 109 vs 88 micrograms/l during therapy), whereas the other haemostatic parameters were not different. Our data indicate a significant activation of the coagulation system in diabetic patients with secondary failure to sulfonylurea drugs, with signs of a prethrombotic state and endothelial cell disturbance.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗