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Biomedical subjects

H Franck

Publications and source records attributed to H Franck.

At least 37 records · Page 2Linked to original sources
PubMed1994

Functional evidence for a glibenclamide-sensitive K+ channel in rat ileal smooth muscle.

The motor activity of gastrointestinal smooth muscle is closely related to the membrane potential. Controlling the membrane potential via modulation of K+ channels is essential for the action of neurotransmitters on smooth muscle. In the present study the effect of the K+ channel activator, lemakalim, on longitudinal smooth muscle of the rat ileum was investigated. Segments of rat ileum were stimulated by the muscarinic receptor agonist, carbachol (10(-6) M). Lemakalim (10(-10) to 3 x 10(-5) M) induced a dose-dependent inhibition of the carbachol-induced contraction. This inhibitory effect of lemakalim was not modified by neural blockade with tetrodotoxin (10(-6) M, n = 9). Glibenclamide (10(-7) to 10(-5) M), a specific blocker of ATP-dependent K+ channels antagonized dose dependently the relaxant effect of lemakalim (IC50: 3.4 x 10(-6) M, n = 11, P < 0.001). In contrast, apamin (10(-7) M, n = 9, n.s.) and charybdotoxin (10(-7) M, n = 9, n.s.), specific blockers of Ca2+-dependent K+ channels and the non-specific K+ channel blocker, tetraethylammonium (10(-4) to 10(-1) M), had no influence on the inhibitory effect of lemakalim. Contractions induced by the Ca2+ channel activator, Bay-K-8644, were completely inhibited by lemakalim (10(-5) M, n = 12). This inhibitory effect was also selectively antagonized by glibenclamide (10(-5) M). Potential non-adrenergic non-cholinergic (NANC) inhibitory mediators like ATP, nitric oxide (NO) or neurotensin showed no sensitivity to glibenclamide. These functional data indicate that the relaxant effect of lemakalim is due to a specific activation of glibenclamide-sensitive K+ channels, which in turn can modulate the activity of dihydropyridine-sensitive (voltage-dependent) Ca2+ channels. A physiological or pathophysiological role of the glibenclamide-sensitive K+ channels in intestinal smooth muscle is discussed; however, they seem not to be involved in the effect of the NANC inhibitory mediators tested.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1994

Osteocalcin in patients with rheumatoid arthritis. A one-year followup study.

OBJECTIVE: To analyze clinical, radiological, and drug (disease modifying antirheumatic drug, DMARD) dependent factors influencing bone turnover in patients with rheumatoid arthritis (RA). METHODS: We investigated in a one-year double blind randomized study comparing intramuscular (im) gold with im methotrexate (MTX), whether the variation of inflammatory activity or functional capacity, the ascending anatomic stage, or DMARD treatments have an influence on bone formation (osteocalcin) in patients with RA. RESULTS: Patients (n = 48) enrolled at the beginning of our study had significantly increased osteocalcin levels (3.45 +/- 0.93-->4.42 +/- 1.39 ng/ml p < 0.02) after one year if inflammatory activity decreased (> or = 1 SD: erythrocyte sedimentation rate (ESR) 26.4 mm/h, C-reactive protein (CRP) 3.8 mg/dl). We found a significant negative correlation of the one-year CRP- (r = -0.44, p < 0.001) or ESR differences (r = -0.45, p < 0.001) with the corresponding osteocalcin differences. This was also evident if these patients were pooled with 15 patients excluded from the double blind study as already receiving DMARD treatment (n = 63; p < 0.01). Patients with impaired functional capacity also had significantly reduced osteocalcin levels (p < 0.01). In both cases, alkaline phosphatase showed no significant differences. CONCLUSIONS: Our data suggest that osteocalcin, a useful followup variable of bone turnover, is changed significantly (p < 0.02) in patients with RA regarding inflammatory activity and functional capacity. In contrast to alkaline phosphatase, a fall in inflammatory activity stimulated and impairment of functional capacity significantly decreased osteocalcin levels in patients with RA.

Adult↗
PubMed1993

Serum osteocalcin and vitamin D metabolites in patients with ankylosing spondylitis.

OBJECTIVES: Osteocalcin is the major non-collagenous protein of bone and is regarded as a specific index of bone formation. The aim of this study was to examine the rate of bone formation measured by osteocalcin in 38 patients with ankylosing spondylitis (AS) and its dependence on various parameters of calcium and phosphate metabolism. METHODS: Serum osteocalcin, alkaline phosphatase, parathyroid hormone, and 1,25-dihydroxyvitamin D were measured in 38 patients with ankylosing spondylitis and in 52 controls. RESULTS: Mean serum osteocalcin was significantly reduced in patients with AS (men 1.7 (1.1) ng/ml; women 1.2 (1.1) ng/ml) compared with the corresponding control groups (men 3.2 (1.3) ng/ml; women 4.1 (1.7) ng/ml). In contrast, alkaline phosphatase was only slightly but significantly higher (135 (44) U/l) in patients with AS than in the corresponding controls (114 (35) U/l). Serum parathyroid hormone (AS 3.1 (0.7) v 2.7 (0.6) mE/ml) and 1,25-dihydroxyvitamin D (AS 64.0 (34.5) v 52.4 (6.7) pg/ml) were slightly but not significantly higher in patients with AS. Consequently, as both hormones are known to stimulate osteocalcin synthesis, they are not responsible for low osteocalcin levels in patients with AS. No significant correlation between alkaline phosphatase and osteocalcin was found. Low serum levels of osteocalcin in patients with AS reflect lower osteoblastic activity in AS. CONCLUSIONS: Bone turnover in patients with AS is characterised by low bone formation in the presence of normal levels of calcium regulating hormones.

Adult↗
PubMed1992

Osteocalcin in patients with rheumatoid arthritis--effect of anatomical stages, inflammatory activity and therapy.

The aim of this study was to investigate whether the degree of inflammatory activity, the anatomical stage and various treatments have an influence on bone turnover in patients with rheumatoid arthritis (RA). Osteocalcin (OC) and other parameters of bone turnover were measured in 131 patients with RA. The mean values of alkaline phosphatase (AP), but not of OC were significantly (P < 0.01) higher in our patients compared to controls. In contrast to AP, OC values increased and correlated significantly (r = +0.33, P < 0.01) with ascending anatomical stage in women not on glucocorticoid treatment. As regards therapy, we found significantly lower OC levels in women receiving steroids compared to controls (P < 0.03) and those being treated with non-steroidal anti-inflammatory drugs (NSAIDs) (P < 0.03), methotrexate (MTX) (P < 0.05), or gold (P < 0.01). Females treated with gold had higher OC levels than patients receiving no antirheumatic drugs (P < 0.03). Furthermore, there was a significantly negative correlation between OC and inflammatory activity [C-reactive protein (CRP)] (r = -0.25, P < 0.003). In conclusion, OC levels were significantly higher (P < 0.032) in patients with advanced (anatomical) stages of RA. In contrast to AP, changes in bone turnover, such as suppression of bone formation by steroids and high inflammatory activity in patients with RA, were easily detected.

Aged↗
PubMed1991

The effect of physical activity on bone turnover in young adults.

Physical activity has been suggested as one of the determinants of bone turnover and to prevent the involutional age related bone loss. However, the degree to which physical exercise is necessary to induce changes in bone turnover and calciotropic hormones have been widely discussed (Williams et al., 1984; Cook et al., 1987; Smith et al., 1985). The aim of this study was to examine the rate of bone formation measured by osteocalcin in 56 healthy volunteers before and after 4 and 8 weeks of physical exercise (PE) and its dependence on various parameters of calcium and phosphate metabolism. The studied group consisting of 44 men and 12 women, mean age 24.8 and 24.3 years, respectively, performed a standardized physical training of 8 weeks. Mean serum osteocalcin levels were significantly (p less than 0.01) reduced after 4 weeks (men: 2.26 +/- 1.8 ng/ml; women: 0.94 +/- 1.6 ng/ml) compared to the values before PE (men: 4.01 +/- 2.18 ng/ml; women: 1.69 +/- 1.7 ng/ml) and returned to normal values after 8 weeks. Similarly, magnesium levels (0.82 mmol/l) decreased significantly (p less than 0.01) after 4 weeks of PE (0.79 mmol/l), returning to normal values after 8 weeks. Concomitantly, there was only a slight, but significant fall of serum calcium from 2.48 +/- 0.07 to 2.45 +/- 0.07 returning to initial values again. Furthermore, serum phosphate increased slightly in men from 1.01 mmol/l to 1.13 and 1.15 mmol/l after 4 and 8 weeks, respectively. In contrast, alkaline phosphatase and serum creatinine remained in the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin in chronic renal failure.

Serum 1,25-dihydroxyvitamin D (1,25(OH)2D) is normal in some patients with chronic renal failure. We studied the question, whether factors known to regulate the serum 1,25(OH)2D concentration such as parathyroid hormone, calcium, phosphate and especially the serum 25 hydroxy vitamin D (25 OH D) concentration are related to circulating levels of serum 1,25(OH)2D in such patients. We found no correlation between these serum parameters and 1,25(OH)2D. Our data indicate that other factors are of more importance for the regulation of serum 1,25(OH)2D in this situation.

Calcifediol↗
PubMed1986

[Alcohol-induced osteopenia].

There is clear evidence of a propensity to fractures and the development of osteomalacia, osteoporosis, and mixed forms in chronic alcoholics. Osteomalacia is associated with impaired vitamin D status, probably due to enzyme induction in liver and kidney and development of a secondary intestinal hyperparathyroidism. The development of osteoporosis is multifactorial, but seems to arise mainly through reduction in bone formation and reduced dietary protein and calcium intake. Low testosterone levels may also contribute to osteoporosis.

Alcoholism↗
PubMed1985

Selective effects of gold (III) on parathyroid hormone-, prostaglandin E2- and guanine nucleotide-sensitive adenylate cyclase.

Gold(III) (Au(III)) up to 0.25 microM increased parathyroid hormone- and prostaglandin E2-sensitive chick osteoblast adenylate cyclase activity without affecting 5'-guanylylimidodiphosphate-stimulated enzyme activity. Au(III) at 5-50 microM inhibited hormone- and nucleotide-mediated activation of adenylate cyclase. Basal adenylate cyclase activity was not influenced by Au(III) in the given concentrations. Treatment of membranes with 5'-guanylylimidodiphosphate prior to incubation with Au(III) prevented the inhibitory effect of Au(III) on adenylate cyclase. Our data suggest that Au(III) alters the response of adenylate cyclase to agonists most likely through interaction with specific sulfhydryl groups associated with the enzyme system.

Adenylyl Cyclases↗
PubMed1982

Parathyroid hormone is normal in renal stone patients with idiopathic hypercalciuria and high fasting urinary calcium.

In a group of patients with idiopathic hypercalciuria and an increased fasting urinary calcium excretion we re-examined the question: does secondary hyperparathy-roididsm exist? Eight out of 51 patients with calcium renal stones had a high calcium excretion in both fasting and in 24 h urines. The carboxyl-terminal immunoreactive PTH (iPTH) values in these patients were 16 +/- 5 ngeq/ml (M +/- SD), no higher than the iPTH values in the other groups, e.g. normocalciuric patients had an iPTH of 23 +/- 8 ngeq/ml. The existence of secondary hyperparathyroidism in a subgroup of stone patients with increased fasting urinary calcium excretion is questionable.

Adolescent↗