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S Hough

Publications and source records attributed to S Hough.

At least 19 recordsLinked to original sources
PubMed2001

Effect of statins on bone mineral density and bone histomorphometry in rodents.

Statins have been postulated to affect bone metabolism. We investigated the effects of different doses of simvastatin (1, 5, 10, and 20 mg. kg(-1). d(-1)), atorvastatin (2.5 mg. kg(-1). d(-1)), and pravastatin (10 mg. kg(-1). d(-1)) administered orally for 12 weeks to intact female Sprague-Dawley rats and the effect of 20 mg. kg(-1). d(-1) simvastatin in sham-operated and ovariectomized rats on femoral bone mineral density (BMD) and quantitative bone histomorphometry (QBH) and compared them with controls. BMD was decreased by 1 mg. kg(-1). d(-1) simvastatin (P=0.042), atorvastatin (P=0.0002), and pravastatin (P=0.002). The effect on QBH parameters differed with different doses of simvastatin (ANOVA, P=0.00012). QBH parameters of both bone formation and resorption were equivalently and markedly increased by 20 mg. kg(-1). d(-1) simvastatin in 2 separate groups of intact rats and were reflected by a relatively unchanged BMD. At lower doses, 1 mg. kg(-1). d(-1) simvastatin decreased bone formation while increasing bone resorption, as reflected by a marked decrease in BMD. Ovariectomized animals receiving 20 mg. kg(-1). d(-1) simvastatin showed no change in BMD relative to the untreated, ovariectomized controls; their increase in bone formation was smaller than in sham-operated rats receiving simvastatin, and there was no change in bone resorption. Dose-response curves of simvastatin for bone formation and resorption differed. These studies indicate that (1) statins decrease BMD in rodents, (2) high-dose simvastatin increases bone formation and resorption, (3) low-dose simvastatin decreases bone formation and increases bone resorption, (4) the effects of simvastatin on QBH differ at different dosages, (5) the effects of simvastatin seen in intact rats are not observed in ovariectomized rats, and (6) simvastatin is unable to prevent bone loss caused by ovariectomy.

Animals↗
PubMed2000

Osteoporosis Clinical Guideline. South African Medical Association--Osteoporosis Working Group.

OBJECTIVE: This Guideline aims to improve the efficacy of both diagnostic and therapeutic interventions for osteoporosis. All health care workers are targeted in the Guideline. A rather detailed summary, which is cross-referenced to the full guideline, is provided to cater for the busy general practitioner. The motivation for the development of this Guideline is based on the facts that: Osteoporosis is a common, costly disease which carries a significant morbidity and mortality, yet is still too often regarded as an inescapable part of normal ageing. Early detection and intervention will be more cost-effective than the treatment of advanced disease. Much confusion exists regarding diagnostic criteria, the assessment of fracture risk, and therapeutic intervention thresholds. A rational approach to drug selection is seldom considered. No consensus guideline on the diagnosis and management of osteoporosis has been published in this country. OUTCOMES: Prevention of fracture and a reduction in morbidity and mortality were the major considerations in the development of this Guideline. Although no formal economic analysis was undertaken, the cost-effectiveness of diagnostic and therapeutic interventions was considered in all recommendations. EVIDENCE: A combination of descriptive, boundary (minimum standards) and algorithmic guidelines was employed. The highest level of evidence (meta-analyses, randomised and controlled studies) was used as far as possible and isolated descriptive studies and expert opinions were largely ignored. A draft guideline was developed, debated at a consensus meeting and finalised on the basis of written comments following the distribution of a second draft. METHODOLOGY: See Annexure B. RECOMMENDATIONS: In the absence of a sound health economic justification for a screening policy, it is recommended that the prevention and treatment of osteoporosis is best managed using a case-finding approach. It is recommended that clinical risk factors--related to bone mineral density (BMD), bone strength or falls--provide indications for further assessment, in particular bone mass measurement. Axial, dual energy X-ray absorptiometry (DEXA) is the preferred technique to assess BMD, to diagnose osteoporosis and to assess rates of bone loss/gain. While the four diagnostic categories proposed by the World Health Organisation (WHO, 1994) provide a practical basis to identify those at risk of fracture, cognisance should be taken of its limitations. We recommend that the BMD of both spine and hip should be measured, that the NHANES III reference data for Caucasians be used for subjects of all races (until local reference ranges for different ethnic groups are established), and that the same absolute thresholds be employed to diagnose osteoporosis in men and women. Recommendations are also made regarding indications for bone mass measurement and selected routine laboratory tests. The differences between diagnostic criteria and intervention thresholds are emphasised. The need to treat should not depend on a BMD value alone, but should also be determined by the patient's age, general health and willingness to consider treatment; the presence of clinical risk factors; prevalent vertebral fractures; and the rate of bone loss/turnover; as well as the cost-effectiveness and side-effects of available treatment. Non-pharmacological measures to improve bone strength include a balanced diet, physical exercise, limiting alcohol consumption, the avoidance of smoking and bone toxic drugs and the prevention of falls. No ideal drug can be recommended for the prevention and treatment of osteoporosis in all patients. The choice of drug is largely determined by the nature of the disease (e.g. antiresorptive agents like calcium (+/- vitamin D) for mild osteopenia, hormone replacement therapy (HRT) or bisphosphonates for moderate bone loss and the addition of a bone formation-stimulating agent in patients with more severe osteoporosis) and the pati

Adult↗
PubMed1998

Fast and slow bone losers. Relevance to the management of osteoporosis.

A low bone mineral density (BMD) is presently regarded as the most important risk factor for the development of osteoporosis. BMD is a function of peak bone mass attained during growth and subsequent age-related bone loss. BMD can be measured accurately and precisely, although the rate of bone loss is more difficult to assess. When axial BMD was measured, the rate of bone loss was shown to increase by 2- to 4-fold at the menopause. Although this rate varies markedly between individuals, it is symmetrically distributed, which argues against the existence of a subpopulation of fast bone losers. Levels of biochemical markers of bone turnover (e.g. osteocalcin, bone specific alkaline phosphatase, deoxypyridinoline) also increase markedly at the menopause, and individuals with a high turnover tend to lose bone more rapidly. Moreover, since increased bone resorption also results in qualitative changes regardless of BMD, a high bone turnover constitutes an independent risk factor. Currently, large intraindividual variations (10 to 40%) in levels of biochemical markers and assay errors still limit our ability to correctly classify individual patients as fast or slow bone losers. The routine use of these markers as a screening tool to predict the risk of osteoporosis in individuals is of limited value, although their selective use in therapeutic decision-making is more promising.

Absorptiometry, Photon↗
PubMed1996

Body fat distribution as a risk factor for osteoporosis.

OBJECTIVE: The aim of this study was to compare the body fat distribution of patients with osteoporosis (OP) with that of an appropriately matched non-OP control group. DESIGN: Case control study. SETTING: Department of Endocrinology and Metabolism, Tygerberg Hospital. Participants. A total of 56 patients with histologically proven idiopathic OP, of whom 39 were women (mean age 61 +/- 11 years) and 17 men (49 +/- 15 years), were compared with 125 age- and sex-matched non-OP (confirmed by dual energy X-ray absorptiometry) subjects, 98 women (60 +/- 11 years) and 27 men (51 +/- 16 years). OUTCOME MEASURES: Anthropometric data, including weight, height, skinfold measurements, mid-upper arm, waist and hip circumferences, as well as elbow breadth. RESULTS: The men and women with OP were significantly shorter (P = 0.04 and P = 0.03 respectively) and of lower body mass (P = 0.04 and P = 0.02 respectively) than the control subjects, although their mean body mass indices were comparable. The OP population had significantly lower skinfold, elbow breadth and arm circumference values, although the majority of subjects in both groups fell within the 15-85th percentiles. Despite their lower body mass, both the OP women (P = 0.009) and men (P = 0.002) had significantly higher waist/hip ratios than corresponding controls. CONCLUSION: Whatever the underlying pathogenesis, this new finding suggests that, should these results be confirmed by larger studies, OP can be added to the list of diseases associated with a waist fat distribution.

Aged↗
PubMed1993

Survival of bull spermatozoa seeded and frozen at different rates in egg yolk-tris and whole milk extenders.

Six factorially arranged experiments were designed to study effects of seeding, freezing, and thawing rates in whole milk and egg yolk-Tris extenders commonly used for commercial cryopreservation of bull sperm. In these extenders, semen normally is supercooled to -13 or -14 degrees C unless the sperm are seeded. When sperm were supercooled or seeded, either mechanically or with immobilized silver iodide, and frozen to -196 degrees C, the postthaw percentages of motile sperm were 59, 57, and 64%, respectively. Freezing rates of -15, -25, and -35 degrees C/min gave similar sperm survival rates and were superior to -5 degrees C/min. For milk, the critical freezing temperature extended to -75 degrees C before transfer to liquid nitrogen gave good results. For egg yolk-Tris extender, transfer to liquid nitrogen was less critical once -50 degrees C had been attained. Thawing of sperm in water baths at 25 and 45 degrees C gave similar results, and both temperatures were superior to 5 degrees C. The postthaw percentage of motile sperm in egg yolk-Tris was equal or superior to that of sperm frozen in milk. A freezing rate of -15 degrees C/min to -100 degrees C and thawing at 25 degrees C consistently gave good results.

Animals↗
PubMed1992

Protein kinase C modulates parathyroid hormone- but not prostaglandin E2-mediated stimulation of cyclic AMP production via the inhibitory guanine nucleotide binding protein in UMR-106 osteosarcoma cells.

In UMR-106 osteosarcoma cells we found that PTH activated both the cAMP/protein kinase A and the Ca(2+)-dependent phosphoinositide/protein kinase C (PKC) pathways, but prostaglandin E2 (PGE2) activated only the cAMP pathway. Activation of PKC by the phorbol ester PMA had no effect on cAMP production but enhanced PTH-stimulated cAMP production by 50% or more; the effect on PGE2-induced cAMP was negligible. Inhibition of the alpha-subunit of the inhibitory guanine nucleotide binding protein (Gi) by pertussis toxin pretreatment also enhanced PTH-mediated cAMP production but had no effect on PGE2-induced cAMP production. These results suggest that although PTH-mediated adenylate cyclase activity is regulated via both the stimulatory (Gs) and inhibitory (Gi) guanine nucleotide binding proteins, only Gs regulates PGE2-mediated adenylate cyclase activity in UMR-106 cells. Costimulation with pertussis toxin and PMA did not increase PTH-stimulated cAMP production above that obtained with PMA alone. This implies a similar target of action for pertussis toxin and PMA, that is, the alpha-subunit of Gi. The alpha-subunit of Gi was found to be a substrate for in vitro PKC phosphorylation of membrane fractions from UMR-106 cells, seen as a +/- 40 kD band on SDS-PAGE. Stimulation of in situ 32P-labeled cells with either PMA or PTH also enhanced incorporation of 32P into the 40 kD band. Using the peptide antisera AS/7 and EC/2, we showed that pertussis toxin-labeled subunits of both Gi1 alpha/Gi2 alpha and Gi3 alpha could be immunoprecipitated, respectively, but immunoprecipitation of membrane proteins after in situ phosphorylation and stimulation with PMA precipitated only Gi2 alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylate Cyclase Toxin↗
PubMed1992

Biochemical changes in bull spermatozoa during capacitation in vitro.

To evaluate the metabolic changes of bull spermatozoa (SPZ) during capacitation in vitro, SPZ were incubated for 0, 5 or 10 hours in the presence (co-culture) and absence (control) of monolayers of bovine oviduct epithelial cells, which promote capacitation-like changes in vitro. There was little change in the oxygen uptake of the SPZ after 5 hours, but after 10 hours there was a decrease, particularly in the co-cultured sample. After 5 hours there was little change in the cyclic adenosine monophosphate (cAMP) concentration of the co-culture or control SPZ, but by 10 hours the levels of cAMP decreased in both the co-cultured and control SPZ (P=0.06). The concentration of adenosine triphosphate (ATP) was somewhat decreased after 5 hours in both the co-cultured and control SPZ and the percentage of decline was much higher after 10 hours. Overall, there was no significant change in oxygen uptake or cAMP and ATP levels specifically associated with capacitation of bull SPZ.

Journal Article↗
PubMed1991

A procedure for cryopreservation of hamster oocytes yielding highly conserved oocytes suitable for sperm penetration tests.

Hamsters were superovulated and their oocytes frozen in Dulbecco's phosphate-buffered saline containing 10% fetal calf serum and 1.5 molar 1,2-propanediol. In several experiments, 94% of the hamster oocytes survived freezing and were equivalent to fresh oocytes in sperm penetration. In routine use of the procedure described, also 94% of 1,340 frozen-thawed oocytes were satisfactory for sperm penetration of several species. Frozen oocytes eliminate problems and costs of maintaining hamster colonies with variable responses on individual days.

Analysis of Variance↗
PubMed1990

Platelet activating factor activity in the phospholipids of bovine spermatozoa.

Platelet activating factor (PAF) has been detected in sperm from several mammalian species and can affect sperm motility and fertilization. Because bovine sperm contain a high percentage of ether-linked phospholipid precursors required for PAF synthesis, a study was undertaken to determine the PAF activity of bovine sperm phospholipids. Total lipids of washed, ejaculated bull sperm were extracted, and phospholipids were fractionated by thin-layer chromatography. Individual phospholipid fractions were assayed for PAF activity on the basis of [3H]serotonin release from equine platelets. PAF activity was detected in the PAF fraction (1.84 pmol/mumol total phospholipid) and in serine/inositol (PS/PI), choline (CP), and ethanolamine phosphoglyceride (EP) and cardiolipin (CA) fractions. Activity was highest in the CP fraction (8.05 pmol/mumol total phospholipid). Incomplete resolution of PAF and neutral lipids may have contributed to the activity in the PS/PI and CA fractions, respectively. Phospholipids from nonsperm sources did not stimulate serotonin release. Platelet activation by purified PAF and by sperm phospholipid fractions was inhibited by the receptor antagonist SRI 63-675. These results indicate that bovine sperm contain PAF and that other sperm phospholipids, especially CP and EP, which are high in glycerylether components, are capable of receptor-mediated platelet activation.

Animals↗
PubMed1988

Perceiver bias in the processing of human faces: neuropsychological mechanisms.

Previous research has suggested that in face-to-face contexts perceivers are biased to judge the side of the poser's face to their left as more similar to the full face than the side to their right. Traditional explanations of the perceiver bias have presumed that it is a visual field effect, with the side of the poser's face falling within the perceiver's left visual field dominating impressions of the full face. In this study, five experiments are reported. In the first experiment, the validity of the perceiver bias phenomenon was supported. The remaining experiments examined three alternative accounts of the neuropsychological processes that underlie the perceiver bias. No support was obtained for the visual field explanation, nor for an account of the bias as due to asymmetry in gaze patterns. Support was obtained for an account emphasizing a hemispatial bias in central processing. Despite equivalent intake of information from both sides of space, the brain may differentially weight information as a function of hemispatial origin. Practical and theoretical implications are discussed.

Adult↗
PubMed1988

Effects of hypervitaminosis A on the bone and mineral metabolism of the rat.

Vitamin A toxicity has been associated with alterations in mineral metabolism and may result in osteopenia, fractures, deformities, and growth arrest. The pathogenesis of the bone lesions that occur in vitamin A toxicity is, however, ill defined and was examined in the present study. The administration of pharmacological doses of vitamin A to growing male rats resulted in weakness and spontaneous fractures. Undecalcified bone histology of vitamin A toxic animals was characterized by increased bone resorption, osteoclastosis, a paucity of trabecular surfaces covered with osteoid, and lesions which appear to be pathognomonic of hypervitaminosis A. The serum calcium and magnesium levels of vitamin A-toxic animals were unremarkable, but serum phosphate levels were significantly higher than control values. Urinary hydroxyproline excretion reflected bone histology and was significantly increased in experimental rats. Circulating levels of the potent bone resorbers, PTH, 1,25-dihydroxyvitamin D, and 25-hydroxyvitamin D, were, however, comparable in vitamin A-toxic and control animals, suggesting a possible direct effect of vitamin A on bone. Subsequently, the effects of vitamin A (retinol) on in vitro collagen synthesis (incorporation of [3H]proline into collagen) and bone resorption (45Ca release from bone) were examined using a fetal rat calvarial culture. Retinol added to the culture medium for 20-24 h in concentrations ranging from 0.5-10 micrograms/ml selectively inhibited collagen synthesis in a dose-dependent fashion. Higher concentrations of retinol were toxic and resulted in a general inhibition of protein synthesis. Bone resorption was stimulated by 0.5 and 2.5 micrograms/ml retinol. We conclude that vitamin A toxicity in rats causes bone lesions, the genesis of which can be explained, at least in part, by a direct effect of the vitamin on skeletal tissue.

Alkaline Phosphatase↗