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Biomedical subjects

C Day

Publications and source records attributed to C Day.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Acute effect of benfluorex on glucose metabolism.

The antihyperlipidaemic agent benfluorex [1-(3-trifluoromethylphenyl)-2-(2-benzoyl-oxyethyl)-aminopropane] and its metabolite S422 [1-(3-trifluoromethylphenyl)-2-(2-hydroxyethyl)-aminopropane] were examined for an acute (after 1-2 hr) effect on glucose metabolism in normal rats. Enteral administration of benfluorex (25 mg/kg) did not affect basal plasma glucose and insulin concentrations. However, enteral and intravenous glucose tolerance were modestly improved without enhancing the insulin response to glucose. Hepatic gluconeogenesis from lactate was not acutely altered by benfluorex (25 mg/kg) in vivo or by S422 (1 mM) in vitro, but S422 (1 mM) slightly reduced (by 11%) hepatic glycogen mobilization in vitro after 2 hr. S422 (1 mM) increased (by 47%) glucose oxidation by diaphragm muscle in vitro. The effect was additive to that of insulin. Anaerobic glucose metabolism and glycogenesis of diaphragm muscle were not affected by S422. The results suggest that benfluorex can acutely improve glucose tolerance associated with increased glucose oxidation by muscle.

Animals↗
PubMed1992

Demonstration of the distribution of coxsackie virus RNA in neonatal mice by non-isotopic in situ hybridization.

A simple method for the demonstration of Coxsackie virus RNA by in situ hybridization is described. Oligonucleotides complimentary to conserved sequences of Coxsackie B genome were synthesised and labelled with digoxigenin using commercially available reagents. In addition to detecting all five Coxsackie B strains examined, six strains of Coxsackie A were also demonstrated by these probes. Using one of the oligonucleotides separately it was possible to distinguish Coxsackie A strains from the strains of Coxsackie B virus examined. This study demonstrates the presence of viral RNA in mice tissues showing morphological evidence of damage, confirming the suspected tropisms of these viruses. The method described is directly applicable to the study of the presence of these viruses in human tissue from diseases where a viral aetiology is suspected.

Animals↗
PubMed1992

Engineered disulfide bond greatly increases specific activity of recombinant murine interferon-beta.

Unlike other species of interferon-beta (IFN-beta) mouse (Mu) IFN-beta has no naturally occurring intramolecular disulfide bond. When expressed in Escherichia coli, MuIFN-beta appears to exhibit instability and low activity. To increase its activity, we engineered a pair of cysteines into recombinant MuIFN-beta to test whether this change would improve its antiviral activity. In the absence of detailed structural data, the optimal placement of cysteines was determined by sequence comparison with other species of IFN-beta. While MuIFN-beta has only a single cysteine (at position 17), other species of IFN-beta have three cysteines, at positions 17, 31, and 141 (numbering based on consensus sequence), a disulfide bond being formed between the latter two residues. Thus, we introduced cysteines into MuIFN-beta at positions 29 and 136, which correspond to positions 31 and 141 of the consensus sequence. When the variant form of MuIFN-beta was expressed in bacteria and purified, we found that the additional cysteines greatly increased the antiviral activity. Further improvement was obtained by replacement of the Cys-17 with a serine. In this manner a specific activity approximately 15-fold that of the wild-type recombinant molecule was achieved.

Animals↗
PubMed1992

The nucleotide sequences of wild-type coxsackievirus A9 strains imply that an RGD motif in VP1 is functionally significant.

We have shown previously that, compared to other enteroviruses, the coxsackievirus A9 (CAV-9) prototype strain, Griggs, contains a C-terminal extension to the capsid protein VP1 and that within this extension there is an RGD (arginine-glycine-aspartic acid) motif. To determine whether these features are found in other CAV-9 strains and therefore analyse whether they are likely to be functionally important, we have determined the nucleotide sequence of the appropriate region from five strains, isolated over a 25 year period. The results indicate that there is considerable diversity between the strains and there is little correlation between nucleotide sequence identity and date of isolation. All isolates exhibit the VP1 extension and although its amino acid sequence is otherwise variable, the RGD motif is common to all. This conservation of sequence, within a region which can otherwise vary, implies that the RGD sequence must be functionally significant. The VP1 extension shows similarity to sequences found in foot-and-mouth-disease virus strains and to part of the precursor of the cellular protein, human transforming growth factor beta, and the possible significance of these observations is discussed.

Amino Acid Sequence↗
PubMed1992

Effect of metformin on glucose metabolism in the splanchnic bed.

1. Use of the antihyperglycaemic agent, metformin, is often associated with a small rise in circulating lactate. This study investigates the source of the lactate and examines the effect of metformin on glucose metabolism by the intestine and liver of rats. 2. Changes in plasma glucose and lactate were measured in the inferior vena cava (IVC), hepatic portal vein (HPV), hepatic vein (HV) and aorta (A) after intrajejunal administration of metformin (50 and 250 mg kg-1) without and with glucose (2 g kg-1). 3. Metformin 250 mg kg-1 reduced the hyperglycaemic response to a glucose challenge, associated with a greater reduction of glucose concentrations in the HPV (average decrease of 33% at 60 and 120 min) than at other sites. 4. Both doses of metformin increased lactate concentrations in the glucose-loaded state: the highest concentration (2.5 fold increase) was recorded in the HPV 60 min after administration of 250 mg kg-1 metformin, with a high lactate concentration persisting in the HV at 120 min. Metformin 250 mg kg-1 also increased lactate concentrations in the basal state, with highest concentrations (2 fold increase) in the HPV. 5. Two hours after intrajejunal administration of metformin, 50 mg kg-1, rings of tissue from the small intestine showed an average 22% decrease in glucose oxidation ([14C]-glucose conversion to 14CO2) and a 10% increase in lactate production. Since glucose metabolism in the gut is predominantly anaerobic, metformin caused an overall 9.5% increase of intestinal glucose utilization.6. Metformin, 10-6 and I0- mol 1', did not significantly alter glucose oxidation or lactate production by isolated hepatocytes, but a very high concentration of metformin (102 mol 1') increased lactate production by 60%.7. The results support the view that metformin increased intestinal glucose utilization and lactate production by the intestine. Under basal conditions there was net extraction of lactate by the liver but not after an enteral glucose load.

Animals↗
PubMed1990

Traditional plant treatments for diabetes. Studies in normal and streptozotocin diabetic mice.

The effects on glucose homeostasis of eleven plants used as traditional treatments for diabetes mellitus were evaluated in normal and streptozotocin diabetic mice. Dried leaves of agrimony (Agrimonia eupatoria), alfalfa (Medicago sativa), blackberry (Rubus fructicosus), celandine (Chelidonium majus), eucalyptus (Eucalyptus globulus), lady's mantle (Alchemilla vulgaris), and lily of the valley (Convallaria majalis); seeds of coriander (Coriandrum sativum); dried berries of juniper (Juniperus communis); bulbs of garlic (Allium sativum) and roots of liquorice (Glycyrhizza glabra) were studied. Each plant material was supplied in the diet (6.25% by weight) and some plants were additionally supplied as decoctions or infusions (1 g/400 ml) in place of drinking water to coincide with the traditional method of preparation. Food and fluid intake, body weight gain, plasma glucose and insulin concentrations in normal mice were not altered by 12 days of treatment with any of the plants. After administration of streptozotocin (200 mg/kg i.p.) on day 12 the development of hyperphagia, polydipsia, body weight loss, hyperglycaemia and hypoinsulinaemia were not affected by blackberry, celandine, lady's mantle or lily of the valley. Garlic and liquorice reduced the hyperphagia and polydipsia but did not significantly alter the hyperglycaemia or hypoinsulinaemia. Treatment with agrimony, alfalfa, coriander, eucalyptus and juniper reduced the level of hyperglycaemia during the development of streptozotocin diabetes. This was associated with reduced polydipsia (except coriander) and a reduced rate of body weight loss (except agrimony). Alfalfa initially countered the hypoinsulinaemic effect of streptozotocin, but the other treatments did not affect the fall in plasma insulin. The results suggest that certain traditional plant treatments for diabetes, namely agrimony, alfalfa, coriander, eucalyptus and juniper, can retard the development of streptozotocin diabetes in mice.

Animals↗
PubMed1990

Hypoglycaemic effect of Momordica charantia extracts.

The hypoglycaemic effect of orally administered extracts of fruits of cultivated Momordica charantia (karela) was examined in normal and streptozotocin diabetic mice. In normal mice, an aqueous extract (A) lowered the glycaemic response to both oral and intraperitoneal glucose, without altering the insulin response. This aqueous extract (A) and the residue after alkaline chloroform extraction (B) reduced the hyperglycaemia in diabetic mice at 1 hour. Material recovered by acid water wash of the chloroform extract remaining after an alkaline water wash (D) produced a more slowly generated hypoglycaemic effect. The results suggest that orally administered karela extracts lower glucose concentrations independently of intestinal glucose absorption and involve an extrapancreatic effect. Two types of hypoglycaemic substances with different time dependent effects are indicated.

Animals↗