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Biomedical subjects

C Day

Publications and source records attributed to C Day.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effect of the antiobesity agent sibutramine in obese-diabetic ob/ob mice.

BACKGROUND: Sibutramine is a reuptake inhibitor of 5-hydroxytryptamine and noradrenaline, being developed as a treatment for obesity. OBJECTIVE: To investigate the effect of sibutramine on glucose homeostasis in obese-hyperglycaemic insulin-resistant ob/ob mice. DESIGN: Sibutramine 5 mg/kg once daily was administered orally to ob/ob mice for six weeks. RESULTS: Sibutramine treatment decreased body weight gain by 12% without a significant overall change in daily food intake. Sibutramine reduced the hyperinsulinaemia by 31%, and lowered plasma non-esterified fatty acids (NEFA) by 17%. Basal plasma glucose concentrations were not significantly altered by sibutramine, but glucose concentrations fell more rapidly after an i.p. glucose challenge, despite lower insulin concentrations. The rate of insulin-induced glucose disappearance was increased by 10% during sibutramine treatment. First administration of sibutramine, 5 mg/kg, did not acutely alter basal plasma glucose, insulin or NEFA concentrations in ob/ob mice, although NEFA concentrations were raised after 24 h. CONCLUSION: The results indicate that chronic administration of sibutramine can reduce weight gain, lower NEFA concentrations, decrease hyperinsulinaemia and ameliorate the insulin resistance of ob/ob mice.

Animals↗
PubMed1998

The development of a community child and family mental health service.

The Community Child and Family Service is a primary care and community-based child mental health service working in a socio-economically disadvantaged area of inner London. This paper outlines the strategic framework and value base from which the service has developed. The clinical projects set up by the service in general practice, community and education settings are described, as are the training and supervision programmes that have been undertaken. The framework for evaluating the clinical and economic outcomes of the projects is outlined. There has been a positive response from purchasers, providers and clients to the introduction of this Service. The relationship between community- and hospital-based child mental health services is discussed, as is the future direction of the Service.

Child↗
PubMed1998

A case of risperidone overdose in early schizophrenia: a review of potential complications.

Deliberate drug overdose is a frequent occurrence in patients with schizophrenia. Typical antipsychotic medications can be lethal at doses 5 times the recommended therapeutic range. Clozapine, an atypical antipsychotic, can be toxic at doses 4 times a moderate dose. Little is known about the lethal effects of the novel antipsychotic risperidone, despite the fact that it is now one of the most widely prescribed antipsychotics in North America. To date, only 1 death attributable to risperidone overdose has been reported. The case presented here documents adverse cardiac effects in a 28-year-old man who intentionally ingested 24 mg of risperidone--4 times the recommended dose. A potential drug interaction with fluvoxamine and the role of active metabolites are discussed.

Adult↗
PubMed1997

Effect of rhBMP-2 on the osteogenic potential of bone marrow stromal cells from an osteogenesis imperfecta mouse (oim).

To understand whether osteogenesis imperfecta (OI) could result from defective differentiation of osteoprogenitor cells, we investigated the osteogenic potential of bone marrow stromal cells from a mouse model of human OI (oim). Bone marrow was flushed from the femurs and tibias of oim and normal littermates using a syringe with Dulbecco's modified Eagle's medium, and cells were allowed to adhere to flasks. Adherent cells were trypsinized and passaged weekly at a 1:4 split. The established stromal cells were assessed for collagen synthesis, alkaline phosphatase, and osteocalcin production in the presence or absence of rhBMP-2. The stromal cells were also assessed for mineralization by Von-Kossa staining and for exogenous gene transfer using adeno-lacZ and a retroviral vector. The bone marrow stromal cells from oim mice synthesized alpha 1(I) homotrimers as expected, whereas the stromal cells from the normal littermates synthesized alpha 1(I)2 alpha 2(I) heterotrimers. The bone marrow stromal cells exhibited low levels of alkaline phosphatase activity under basal conditions: upon treatment with rhBMP-2, the level of the alkaline phosphatase activity increased approximately 40-fold. Cytochemical staining of the cells confirmed the expression of alkaline phosphatase by the oim stromal cells and its augmentation by rhBMP-2. Osteocalcin production in the stromal cells was also enhanced approximately threefold by rhBMP-2. oim stromal cells grown in the presence of beta-glycerophosphate and ascorbic acid demonstrated Von-Kossa-positive solid deposits after 3 weeks in culture. Ten days after infection with adeno-lacZ, approximately 70% of oim stromal cells expressed the transgene product, and after infection with a retrovirus, approximately 20% of the cells expressed the transgene. These data indicate that bone marrow stromal cells, have osteogenic potential, and also the potential to be transduced with exogenous genes. Under basal conditions, however, the stromal cells from oim mice exhibited significantly lower levels of alkaline phosphatase activity than their normal littermates.

Alkaline Phosphatase↗
PubMed1997

Antihyperglycaemic effect of saccharin in diabetic ob/ob mice.

1. The effect of chronic saccharin (benzosulphimide) consumption on glucose homeostasis was examined in normal lean +/+ mice and genetically obese hyperglycaemic insulin-resistant ob/ob mice. 2. Consumption of a 5% (w/v) sodium saccharin solution for 7 weeks prevented the development of hyperglycaemia, improved glucose tolerance (area under curve decreased by 51%), reduced the extent of hyperinsulinaemia (by 21%), and reduced excessive weight gain (by 18%) in ob/ob mice. 3. Consumption of 5% (w/v) sodium saccharin temporarily decreased hyperphagia at the beginning of treatment, decreased hepatic glycogen content (by 47%), increased abdominal muscle glycogen content (by 82%), but did not significantly alter the hypoglycaemic response to exogenous insulin in ob/ob mice. 4. Consumption of a 1% (w/v) sodium saccharin solution did not prevent the development of hyperglycaemia in ob/ob mice. 5. Normal lean +/+ mice consuming 5% (w/v) sodium saccharin solution showed a marginal decrease (by 8%) in glycaemia, and glucose tolerance was improved (area under curve decreased by 30%) without a significant change in the insulin response to glucose or the hypoglycaemic effect of exogenous insulin. 6. These results suggest that chronic consumption of saccharin can defer the development of hyperglycaemia and improve glucose homeostasis in insulin-resistant ob/ob mice through a mechanism that is independent of insulin.

Animals↗
PubMed1997

Hb T-Cambodia, a beta chain variant with the mutations of Hb E and Hb D-Punjab, confirmed by DNA analysis.

Hemoglobin variants with two amino acid substitutions affecting one globin chain are relatively rare. Hb T-Cambodia, a doubly substituted beta-globin variant, was characterized previously by amino acid sequencing as having sequence alterations in beta 26 (beta 8)Glu-->Lys and beta 121(GH4) Glu-->Gln (1). It is a variant that migrates cathodic to Hb A2 on alkaline electrophoresis and with Hb A on acid citrate agar electrophoresis. We report here the mutations of Hb T-Cambodia at the nucleotide level using DNA sequencing, in beta-globin gene codon 121 (GAA-->CAA) and in codon 26 (GAG-->AAG). These are the mutations of Hb D-Punjab and Hb E, respectively.

Adult↗
PubMed1995

Synthesis of stereoisomers of antithrombotic nipecotamides.

The stereoisomers of alpha,alpha'-bis[3-(N,N-diethylcarbamoyl)-piperidino]-p-xylene (1) were synthesized. Rac ethyl nipecotate was resolved by diastereomeric (-)-D- and (+)-L-tartrate salt formation. The enantiomeric esters were hydrolyzed to the corresponding nipecotic acids, which were then converted into t-BOC derivatives. Treatment of the latter with diethylamine/isobutyl chloroformate and removal of the t-BOC protecting group afforded (R)- and (S)-N,N-diethylnipecotamides. Condensation of the latter with alpha,alpha'-dibromo-p-xylene gave (R,R)- and (S,S)-1. The meso-diastereomer was obtained by stereospecific synthesis in addition to our earlier procedure involving fractional crystallization of the diastereomeric mixture obtained by synthesis. The latter was resolved earlier into 1A, 1B, and 1C using chiral high-performance liquid chromatography (HPLC). Based on the stereospecific synthesis now achieved, 1A and 1B are assigned the configurations, (R,R) and (S,S) respectively, and 1C is assigned the meso configuration. The (R,S) structure of the latter is also confirmed by X-ray crystallography.

Chromatography, High Pressure Liquid↗
PubMed1995

Plasma sialic acid in animal models of diabetes mellitus: evidence for modulation of sialic acid concentrations by insulin deficiency.

An elevated circulating sialic acid concentration is a risk factor for cardiovascular disease. Serum sialic acid levels are elevated in NIDDM but not in uncomplicated IDDM. To study why sialic acid is increased in some types of diabetes, we assayed plasma sialic acid in various animal models of diabetes: obese (ob/ob) mice, before and after streptozotocin treatment, neonatal streptozotocin-treated (nSTZ) rats, and diabetic BB rats during and after insulin treatment. In obese mice, which exhibit moderate hyperglycemia and marked hyperinsulinemia, plasma sialic acid was decreased by 45% (fed) and 42% (fasted), compared to lean controls. Fasting reduced plasma glucose and insulin but increased sialic acid in the obese and lean mice. There was a negative correlation (r = -0.84, P < 0.001) between log plasma insulin and sialic acid in the lean and obese mice. The plasma sialic acid:globulin ratio was reduced by 35% in obese mice vs. lean controls, indicating that there may be altered sialylation of glycoproteins in obese mice. Streptozotocin treatment of obese and lean mice reduced plasma insulin but increased sialic acid. In nSTZ rats, hyperglycemia was associated with mild hypoinsulinemia, but not significantly different from control animals, and sialic acid was not altered. In diabetic BB rats, plasma glucose rose from a mean of 4.9 to 23.5 mM 48 hr after insulin withdrawal but sialic acid did not change. We conclude that an elevated plasma sialic acid level is associated with marked insulin deficiency, rather than hyperglycemia per se. The magnitude and speed of this change in sialic acid varies between species.

Animals↗
PubMed1994

Viral leakage risk differences in latex condoms.

Through use of a new bacteriophage assay capable of detecting a single viral plaque-forming unit (PFU), viral leakage through multiple replicates of several types of latex condoms has been evaluated. Stocks were used that had been preserved from a previous large study in which viral leakage had been assessed preliminarily in several brands. In the present research, much larger numbers of replicates--on the order of magnitude of 100 condoms per brand--were used. Leakage was demonstrated in single production lots of each of seven brands of condoms. With one notable exception, percent leakage ranged from 0.9 to 22.8%; 100% of the specimens of one profoundly flawed brand leaked. All test condoms were subjected to conditions intended to model these prevailing during coitus. Because the condoms used in this study were aged, current stocks of two widely sold brands were tested for comparison. Of these, 11.8% of one brand leaked, 25.7% of the other. The relevance of the results, which gave a high, albeit physiologically appropriate, challenge to the test brands, is discussed--so too is the significance to condom users of results deriving from a leakage assay of exquisitely high sensitivity.

Bacteriophage phi X 174↗
PubMed1994

Attitudes of dog owners to neutering pets: demographic data and effects of owner attitudes.

A survey of the attitudes of dog owners to desexing male and female dogs was conducted in the Brisbane area. Over 15,800 replies (35% response) were returned for analyses and included both demographic and attitude data. The most common reasons given by owners for not having the dog desexed were that it was unnecessary or they wanted to breed from it or could not afford it or did not agree with it or that the dog was too old or it might get fat. Nearly twice as many male owners agreed that desexing male dogs removed maleness and also more males agreed with the question "Do you equate dog sexuality with human sexuality?" Female owners were more aware than males that their female dogs did not need to have a season (oestrus) or a litter before being desexed. More male owners thought that desexing changed a male or female dog's personality. A disturbing fact was that 61.1% of male owners and 47.3% of female owners would now not have their dog desexed if it had not already been done. More male than female dog owners were ignorant about whether desexing changed personality, made dogs frustrated, or if female dogs should have a season or a litter before desexing. The study showed a gender bias in owner attitudes to all the attitude questions.

Animals↗
PubMed1993

Retrospective follow-up study of foundry and engine plant workers.

A retrospective follow-up study of 21,013 workers employed at a foundry and two engine manufacturing plants was conducted to determine if these workers had an unusual mortality experience. A total of 2,235 deaths occurred during the follow-up period of 1970-1987. Mortality from all causes was lower than expected. Men experienced a 6-13% excess of lung cancer deaths, depending on the choice of the comparison group. The data displayed evidence of a positive trend between lung cancer mortality and increasing duration of employment (p = 0.008). White men experienced a statistically significant excess of deaths from stomach cancer (standardized mortality ratio [SMR] = 158; 95% confidence interval [CI] = 101-234). Black men had increased mortality from pancreatic cancer, especially among engine plant workers (SMR = 303; CI = 121-624), and an excess of prostate cancer, concentrated among foundry workers (SMR = 234; CI = 112-430).

Adult↗
PubMed1993

Topical toremifene: a new approach for cutaneous melanoma?

The distribution of topically applied toremifene (0.5-1 mg/day for 5 days) in the ultraviolet B (UVB)-induced Monodelphis domestica opossum melanoma model was examined. The mean concentration of toremifene measured in the skin was 1200 nmol/g, or > 500 times that detected in any other tissues (blood, brain, liver, testicles, heart, uterus, eyes). In plasma, toremifene could be detected in only one animal of six (0.04 nmol/ml). Intraperitoneal administration of 0.5 mg toremifene daily for 5 days in three female animals resulted in a mean uterus concentration of 22.9 nmol/g, or 400-fold that achieved by topical administration of 0.5 mg/day in three other female Monodelphis (0.05 nmol/g). The cytostatic effect of toremifene was studied in three human melanoma cell lines and three experimental cell lines derived from UVB-induced melanocytic nevi in M. domestica. Toremifene had a cytostatic effect on all cell lines (50% growth-inhibitory concentrations, 5.8-9.6 microM). Topical toremifene administration yields high local concentration with minimal systemic distribution. In addition, toremifene has a cytostatic effect at achievable concentrations in a variety of melanomatous cell lines.

Administration, Topical↗