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Biomedical subjects

C Day

Publications and source records attributed to C Day.

At least 19 recordsLinked to original sources
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↗
PubMed1989

Enterovirus-specific IgM in the diagnosis of meningitis.

Samples of serum from 557 patients with a clinical diagnosis of meningitis or encephalitis and referred to the Epsom Public Health Laboratory during a period of 3 years were tested for enterovirus-specific IgM in a mu capture enzyme-linked immunosorbent assay (ELISA). Enterovirus-specific IgM was detected in 45% samples from all age groups. In the 3-5-year age group, 67% specimens were positive. A notable male predominance (73%) was seen in the age group 0-15 years. As predicted, a seasonal increase in incidence was found in the summer and autumn months. Data from a questionnaire sent to the referring laboratories showed only a 5% enterovirus isolation rate from cerebrospinal fluids when isolation of a virus was attempted. The enterovirus IgM ELISA is a sensitive economical and rapid method for use in the diagnosis of viral meningitis.

Adolescent↗
PubMed1989

Effect of gender on the response to a high fat diet in aging Fischer 344 rats.

The purpose of this study was to describe the effects of high fat (HF) and low fat (LF) diets in male and female Fischer 344 (F344) rats ages 5, 23 and 27 mo. Rats were fed the diet for 3 mo, and then resting metabolic rate, body composition and adipose tissue cellularity were evaluated. Although body mass was greater in rats fed the HF diet, this difference was due to a rapid increase in mass within the first 2 wk. There was no difference in the rate of body mass gain after this period. Resting mass-independent metabolic rate did not significantly differ due to age, diet or gender. In general, percentage fat mass was greater in rats fed the HF diet and in female than in male rats in both diet groups. However, lean body mass (%) was not altered due to diet or age. Cell number of the retroperitoneal depot increased with age and diet between 5 and 23 mo of age in both male and female rats. There was no effect of age, diet or gender on retroperitoneal cell size or gonadal cell number and size. These data suggest that age, gender and diet do not significantly alter the ability of F344 rats to regulate body composition or fat cell proliferation.

Adipose Tissue↗
PubMed1989

Incidental and purposeful random donor blood transfusion. Sensitization and transplantation.

We conducted a prospective study to gauge the frequency and degree of sensitization by transfusion and/or pregnancy in 797 candidates for first renal transplants. Sensitization was proportional to the number of blood transfusions. Multiple transfusions or a history of pregnancy without transfusions had similar effects on sensitization. The combination of transfusion and prior pregnancy resulted in sensitization of 1/3 of the candidates. Patients who were not sensitized and were accepted for 1-haplotype living-related donor grafts or first-cadaver donor grafts were transfused to receive a total of 5 units of packed red blood cells. Parous patients had an undue rate of antibody formation and alternate means of selecting and managing parous women are described. Nonparous candidates had a low rate of sensitization (8%) that did not prove an impediment to obtaining a transplant. Only 2% of prospective LRD graft recipients developed antibody against their intended donor. Transplant patients were generally managed with azathioprine and prednisone. One-haplotype LRD graft survival of protocol patients was 93.7% one year posttransplant, and 82.1% at 5 years. One-year CD graft survival was 77%. There was no reduction in graft survival when the interval between transfusion and transplantation exceeded one year. Random donor transfusion is effective in improving renal graft survival. Some recent multiinstitutional reports indicate a reduction or absence of the transfusion effect with current immunosuppression. Discarding blood transfusion as a preparation for transplantation may be ill-advised pending a prospective study.

Blood Transfusion↗
PubMed1989

Effect of age and gender on thermoregulation.

Previous investigations have shown that during cold exposure 24-mo-old male Fischer 344 (F344) rats do not thermoregulate as well as do 12-mo-old animals. To determine if this deficiency also occurs in female rats, we measured oxygen consumption (thermogenesis) and colonic temperature of male and female rats 5, 23, and 27 mo of age at rest and during 6 h of exposure to 6 degrees C. In addition, nonshivering thermogenesis (NST) was evaluated from the capacity of brown adipose tissue (BAT) mitochondria isolated from cold-exposed rats to bind guanosine 5'-diphosphate (GDP). Neither age nor gender had a significant effect on resting or cold-exposed oxygen consumption expressed on a mass-independent basis (l/kg body mass0.67) or on a lean body mass independent basis (l/kg lean body mass0.67). The drop in colonic temperature in response to cold was greater in the male rats. However, females exhibited increased BAT mass and relatively constant GDP binding with advancing age, whereas males showed decreased mass and GDP binding. Although the data suggest greater NST capacity in the female rats, rates of cold-induced oxygen consumption were similar in older female vs. male rats. Taken together, our data indicate that gender has a significant impact on thermoregulation and that, under the cold exposure conditions of the study, this effect involves differential heat conservation rather than heat production.

Acclimatization↗
PubMed1989

Traditional plant medicines as treatments for diabetes.

More than 400 traditional plant treatments for diabetes mellitus have been recorded, but only a small number of these have received scientific and medical evaluation to assess their efficacy. Traditional treatments have mostly disappeared in occidental societies, but some are prescribed by practitioners of alternative medicine or taken by patients as supplements to conventional therapy. However, plant remedies are the mainstay of treatment in underdeveloped regions. A hypoglycemic action from some treatments has been confirmed in animal models and non-insulin-dependent diabetic patients, and various hypoglycemic compounds have been identified. A botanical substitute for insulin seems unlikely, but traditional treatments may provide valuable clues for the development of new oral hypoglycemic agents and simple dietary adjuncts.

Diabetes Mellitus, Type 2↗
PubMed1989

Glycaemic effects of traditional European plant treatments for diabetes. Studies in normal and streptozotocin diabetic mice.

Twelve plants used for the traditional treatment of diabetes mellitus in northern Europe were studied using normal and streptozotocin diabetic mice to evaluate effects on glucose homeostasis. The plants were administered in the diet (6.25% by weight) and/or as decoctions or infusions in place of drinking water, to coincide with the traditional method of preparation. Treatment for 28 days with preparations of burdock (Arctium lappa), cashew (Anacardium occidentale), dandelion (Taraxacum officinale), elder (Sambucus nigra), fenugreek (Trigonella foenum-graecum), guayusa (Ilex guayusa), hop (Humulus lupulus), nettle (Urtica dioica), cultivated mushroom (Agaricus bisporus), periwinkle (Catharanthus roseus), sage (Salvia officinale), and wild carrot (Daucus carrota) did not affect the parameters of glucose homeostasis examined in normal mice (basal plasma glucose and insulin, glucose tolerance, insulin-induced hypoglycaemia and glycated haemoglobin). After administration of streptozotocin (200 mg/kg) burdock and nettle aggravated the diabetic condition, while cashew, dandelion, elder, fenugreek, hop, periwinkle, sage and wild carrot did not significantly affect the parameters of glucose homeostasis studied (basal glucose and insulin, insulin-induced hypoglycaemia, glycated haemoglobin and pancreatic insulin concentration). Guayusa and mushroom retarded the development of hyperglycaemia in streptozotocin diabetes and reduced the hyperphagia, polydipsia, body weight loss, and glycated haemoglobin. Mushroom also countered the initial reduction in plasma insulin and the reduction in pancreatic insulin concentration, and improved the hypoglycaemic effect of exogenous insulin. These studies suggest the presence of potentially useful antidiabetic agents in guayusa and mushroom.

Animals↗
PubMed1986

Clinical and pharmacologic correlations in cyclosporine-induced gingival hyperplasia.

Cyclosporine-induced gingival hyperplasia was investigated in a clinical study of 100 patients over a period of 2 1/2 years. Seventy percent of the patients exhibited at least mild gingival hyperplasia. For doses within the therapeutic range, no direct correlation was found between the oral dose or the serum trough concentration of cyclosporine and the severity of gingival hyperplasia. The presence of dental plaque was found to be related to the presence of gingival hyperplasia, but only a weak correlation existed between the abundance of plaque and the severity of gingival hyperplasia. Children and especially adolescents had a greater risk of developing cyclosporine-induced gingival hyperplasia than adults had. In 21 patients followed for 1 to 18 months after cessation of cyclosporine therapy, induced gingival hyperplasia was found to be clinically reversible.

Adolescent↗
PubMed1986

Role of adrenal glands in the development of abnormal glucose and insulin homeostasis in genetically obese (ob/ob) mice.

This study evaluates the role of adrenal hormones in the development of hyperinsulinaemia and impaired glucose homeostasis in genetically obese hyperglycaemic C57BL/6J ob/ob mice. Lean (+/?) and obese mice were bilaterally adrenalectomised or sham operated at 5 weeks of age, and glucose tolerance was examined after 7 and 14 days. Adrenalectomy temporarily reduced food intake and body weight gain in lean mice, and improved glucose tolerance without a significant change in plasma insulin concentrations at both intervals studied. In obese mice adrenalectomy permanently reduced body weight gain and food intake to values comparable with lean mice. Glucose tolerance was improved in adrenalectomised obese mice at both intervals studied, resulting in plasma glucose concentrations similar to adrenalectomised lean mice. Plasma insulin concentrations during the tolerance tests were reduced in adrenalectomised obese mice, but remained higher than in lean mice. Adrenalectomy did not improve the poor insulin response to parenteral glucose in obese mice. The results indicate that adrenal hormones play an important role in the development of glucose intolerance and contribute to the hyperinsulinaemia in obese (ob/ob) mice, in part by promoting hyperphagia.

Adrenal Glands↗