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Biomedical subjects

F Ismail

Publications and source records attributed to F Ismail.

45 records · Page 3Linked to original sources

Deranged bone mineral metabolism in chronic alcoholism.

Chronic alcoholic subjects may suffer from osteopenia with either osteomalacia or osteoporosis as the main histologic finding. The reasons may be multifactorial, including nutrition, direct effects of alcohol on bone, and deranged liver function. Seventeen asymptomatic subjects with chronic alcoholism were studied. Serum PTH (carboxyl and midmolecule fragments), 25 hydroxyvitamin D [25(OH)D], 1-25 dihydroxyvitamin D [1-25(OH)2D], and ionized calcium were measured in each subject. In addition to these tests, we employed a sensitive technique of dual photon absorptiometry to measure vertebral bone density and a radioimmunoassay of serum bone gla protein (BGP) to estimate osteoblast function. Our results show that subjects suffering from chronic alcoholism had significantly lower serum 25(OH)D and higher ionized calcium, BGP, PTH (midmolecule) and 1,25(OH)2D while four patients had bone density values below the fracture threshold (0.96 g/cm2). These findings demonstrate that asymptomatic patients with chronic alcoholism have deranged bone mineral metabolism including abnormal BGP and some subjects may even have abnormal dual photon absorptiometry measurements. These particular subjects may be at risk in the future for developing osteopenia and consequent vertebral compression fractures.

Adult↗

1,25-Dihydroxyvitamin D3 modulates glucocorticoid-induced alteration in serum bone Gla protein and bone histomorphometry.

Glucocorticoid excess is associated with alterations in the vitamin D endocrine system. The aim of this study was to assess change in serum bone Gla protein (BGP) after low and high dose cortisone acetate treatment and to assess whether these alterations are altered or attenuated by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] administration. Five groups of rats were studied and compared to a control group [cortisone acetate in doses of 0.2, 3.3, and 5.0 mg/100 g BW; 1,25-(OH)2D3 in a dose of 100 ng/100 g BW; and a combination of 1,25-(OH)2D3 (100 ng/100 g BW) plus cortisone acetate (3.3 mg/100 g BW)]. Each animal received daily sc injections for 27 days. BGP decreased significantly by day 7 in the two groups receiving high doses of cortisone acetate compared to control group values (65.20 +/- 4.38 vs. 150.18 +/- 6.13 ng/ml in the intermediate dose group and 91.57 +/- 5.30 vs. 150.18 +/- 6.13 ng/ml in the high dose group; P less than 0.01); this effect persisted until day 28. Histomorphometry revealed decreased formation and resorption in the two high dose cortisone acetate groups, whereas low dose cortisone acetate produced no histological change. The combination therapy lessens any change in BGP until day 28 when BGP was lower than the control value (P less than 0.01); histomorphometry showed that combination therapy prevents the effect of cortisone acetate by increasing bone formation and resorption. The data demonstrate that high doses of cortisone acetate suppress bone formation and that this is reflected in the low serum BGP values. Thus, BGP may be a marker of glucocorticoid-induced bone disease. 1,25-(OH)2D3 protects against glucocorticoid-induced bone disease and the normal BGP level reflects this.

Animals↗

Serum bone gla protein (BGP) and other markers of bone mineral metabolism in postmenopausal osteoporosis.

Bone gla protein, the vitamin K-dependent protein synthesized by osteoblasts and measured in blood by radioimmunoassay, has been used as an index of the rate of bone turnover. The relationship of bone gla protein with other markers of bone mineral metabolism was determined in 31 untreated postmenopausal women with the osteoporotic syndrome. In addition to serum osteocalcin (BGP) we measured parathyroid hormone (PTH) (carboxyl and mid-molecule fragments), 25(OH)D, alkaline phosphatase, estradiol (E2), estrone (E1), dietary calcium intake, 24 hour urinary calcium excretion, and bone mineral density by CT scan of the lumbar vertebrae. Significant osteopenia was present on CT in untreated postmenopausal osteoporotic women (bone density in 18 out of 31 was below the critical value of 60 mg/cm3). Serum BGP correlated positively with CT scan (r + 0.647, P less than 0.001). CT and age were negatively correlated (r - 0.661, P less than 0.001) while CT and E2 showed a positive correlation (r + 0.554, P less than 0.01). Unexpectedly, BGP and age revealed a significant negative correlation (r - 0.421, P less than 0.05). These findings suggest a state of low bone turnover in this group with untreated postmenopausal osteoporosis.

Adult↗

Hypothalamic-pituitary sarcoidosis. A case report.

A 42-year-old woman suffered from sarcoidosis and hypothalamic-pituitary involvement. When she presented initially, an abnormal chest radiograph and abnormal features on histological examination of the lymph nodes, which showed caseating granulomas, suggested a diagnosis of tuberculosis. Failure to respond to antituberculosis therapy and the progressive development of symptoms of both posterior and anterior pituitary deficiency prompted a review of the initial diagnosis. Subsequent dynamic tests of hypothalamic and pituitary function indicated lesions at both the hypothalamic and pituitary levels. Further tests, including the Kveim reaction, favoured a diagnosis of sarcoidosis. This case illustrates the uncommon association of caseating granulomas with sarcoidosis and documents hypopituitarism due to combined hypothalamic and pituitary disease caused by sarcoid infiltration.

Adult↗

Modulating influence of D,L-propranolol on triiodothyronine-induced skeletal muscle protein degradation.

There is evidence suggesting that thyrotoxicosis increases beta-adrenoreceptor density on some target tissues. We have studied the in vivo effect of D,L-propranolol (a nonselective beta-adrenoreceptor blocking agent) on T3-induced enhancement of in situ proteolysis in fast twitch muscle fibers of the rat. Chronic treatment with T3 as opposed to saline resulted in a 76% enhancement of the rate of in situ muscle proteolysis [0.79 +/- 0.04 (n = 8) compared with 0.45 +/- 0.01 (n = 8) nmol tyrosine/mg muscle . 2 h]. Treatment of rats with both T3 and 2 mg propranolol resulted in a 62% reduction in the T3-induced increment in situ muscle proteolysis [0.58 +/- 0.02 (n = 8) vs. 0.79 +/- 0.04]. This significant inhibition by propranolol of T3-induced enhanced proteolytic rates in vitro suggests that this may comprise one component of the observed beneficial clinical effects of beta-blockade in thyrotoxic myopathy.

Animals↗

Fingerprinting Acinetobacter strains from clinical sources by numerical analysis of electrophoretic protein patterns.

A total of 57 strains of Acinetobacter calcoaceticus was fingerprinted by SDS-PAGE of cellular protein. All strains were also examined by conventional, API and N/F-Tek methods, and antibiotic sensitivity patterns were determined. In general, using the API 20E and N/F-Tek methods, it was possible to assign isolates of A. calcoaceticus to the two accepted "biotypes" or "varieties", A.c. anitratus and A.c. lwoffi, but these methods did not offer useful subdivision of the biotypes. Gel electrophoresis permitted subdivision of the strains into clusters in a manner which suggests that the technique may be valuable in typing strains isolated during outbreaks of infection in hospital.

Acinetobacter↗

A high-molecular-weight cysteine endopeptidase from rat skeletal muscle.

A cytosolic enzyme of high molecular weight (about 500 000), which attacks native or denatured proteins (inter alia, casein, globin and hexokinase) was purified about 1000-fold from mixed rat skeletal muscles, including muscles freed of mast cells by prior treatment of the animals with the degranulator, compound 48/80. Peptides of varying size were generated from radioactively labelled globin, but no free amino acids were formed; free tyrosine was also not released from azocasein. The pH optimum was 7.5 and the presence of an essential cysteine group was suggested because dithiothreitol (1 mM) stimulated the activity and N-ethylmaleimide (5 mM) and p-chloromercuriphenylsulphonic acid (1 mM) were inhibitors. The activity was markedly inhibited by Zn2+ but not by leupeptin, chymostatin or pepstatin. The enzyme was stabilized by ATP, at concentrations as low as 0.1 mM, against inactivation at 42 degrees C. The endopeptidase was clearly separated on gel chromatography from another large protease, also sensitive to Zn2+, but with marked aminopeptidase activity and the properties of hydrolase H. The activity levels of the protease, assayed after chromatography on Sepharose 6B of high-speed supernatant fractions, did not vary significantly in skeletal muscle samples which were derived from denervated, starved, diabetic or hyperthyroid animals, in all of which the abnormal physiological states expressed themselves as enhanced rates of tyrosine released by incubated soleus and extensor digitorum longus muscles. Nevertheless, the enzyme described here may be part of an ATP-dependent, multi-component proteolytic system similar to that already known to be present in reticulocytes.

Adenosine Triphosphate↗

Soluble and particulate forms of muscle alkaline proteinase show differential sensitivity to endogenous inhibitor(s).

Membrane-free washed myofibrils derived from rat skeletal muscle homogenates contained a chymostatin-sensitive protease(s) which acted on associated myofibrillar proteins, at an optimum pH of 8.5, much less rapidly at low ionic strength (insoluble myofilaments) than at high salt concentrations (solubilized proteins). When the myofibrillar fraction was added to the particle-free cytosol prepared from the muscle extracts, proteins of the cytosol were also degraded, but the activity in this case was much more pronounced at low ionic strength. This was because inhibitor(s) of the proteinase present in the cytosol fraction were only effective at high ionic strength when all the myofibrillar (and associated) proteins were in solution. The protease was separated from the bulk of the myofibrillar proteins by gel chromatography at high ionic strength. On dialysis against a low-salt buffer, part of the enzyme was precipitated. The putative cytosolic inhibitor(s) were again only effective on the soluble enzyme at high ionic strength.

Animals↗

Effects of pravastatin and cholestyramine on circulating levels of parathyroid hormone and vitamin D metabolites.

The subjects were 40 hypercholesterolemic patients (mean age, 58 years) receiving a low-fat diet and randomly assigned to treatment with placebo for eight weeks or 40 or 80 mg of pravastatin, 24 gm of cholestyramine, or 40 mg of pravastatin plus 24 gm of cholestyramine daily for 24 weeks. After eight weeks of active treatment, levels of total and low-density lipoprotein cholesterol were significantly reduced and the decline was maintained for the remaining 16 weeks. Parathyroid hormone levels and levels of the vitamin D metabolites 1,25(OH)2D3 and 25(OH)D3 did not change during treatment. The results indicate that 24 weeks of treatment with pravastatin and cholestyramine does not affect calcium metabolism.

Calcifediol↗