The effect of abolition of the endogenous corticosteroid rhythm on the circadian variation in methotrexate toxicity in the rat.

Monitoring of indices of haematological, renal and hepatic toxicity in rats after a single i.v. bolus of methotrexate has shown that they vary with the time of day at which the drug is administered.

Immunoreactive C-peptide in spontaneous syndromes of obesity and diabetes in mice.

Immunoreactive C-peptide was evaluated in the plasma and pancreas of Aston ob/ob and C57BL/KsJ db/db mice in relation to disturbances in pancreatic B-cell function. At 18-24 weeks of age, ob/ob and db/db mice displayed hyperglycaemia (1.6 and 3.

Fusarium as a pathogen. A case report of Fusarium sepsis and review of the literature.

Fusarium species are known to the dermatologist as cutaneous contaminants. Rarely they occur as pathogens. We report a case of disseminated Fusarium moniliforme in a 44-year-old patient with acute lymphocytic leukemia.

Defective diurnal changes of food intake, plasma glucose and insulin in rats with a transplantable islet cell tumour.

Subcutaneous implantation of small fragments of a radiation-induced transplantable rat insulinoma into the subscapular region of 16- to 17-week-old male NEDH rats resulted, over a 22-day period, in the progressive development of marked hyperinsulinaemia and severe hypoglycaemia, despite a compensatory increase in food intake. Diurnal changes were examined at 3-hourly intervals for 24 h in control rats and tumour-bearing rats at 20-21 days after transplantation. The control animals exhibited distinct diurnal changes of food intake, glucose and insulin concentrations.

Effects of cytotoxic drugs and inhibitors of insulin secretion on a serially transplantable rat insulinoma and cultured rat insulinoma cells.

The effects of cytotoxic drugs and inhibitors of insulin secretion were examined in vivo in rats with a radiation-induced transplantable insulinoma, and in vitro using cultured rat insulinoma cells and the derived RINm5F insulin-secreting cell line. Administration of diazoxide to insulinoma-bearing rats resulted in a transient decrease of plasma insulin with a temporary rise of glucose concentrations. Mannoheptulose and somatostatin failed to affect the marked hyperinsulinaemia and hypoglycaemia.

Metabolic effects and secretory properties of a radiation-induced transplantable rat insulinoma.

The metabolic effects and secretory properties of a radiation-induced transplantable insulinoma were examined in 16-17 week old NEDH rats. Subcutaneous subscapular implantation of tumour fragments resulted in hyperphagia, increased body weight gain, marked hyperinsulinaemia and severe hypoglycaemia, with the resulting death of the recipient by 27 days. Ultimate tumour size was 2.

The biotransformation and urinary excretion of dexamethasone in equine male castrates.

The pro-drugs of dexamethasone, a potent glucocorticoid, are frequently used as anti-inflammatory steroids in equine veterinary practice. In the present study the biotransformation and urinary excretion of tritium labelled dexamethasone were investigated in cross-bred castrated male horses after therapeutic doses. Between 40-50% of the administered radioactivity was excreted in the urine within 24 h; a further 10% being excreted over the next 3 days.

Urinary metabolites of caffeine in pregnant women.

In a study of caffeine and its metabolites in pregnant and non-pregnant women, on average 56.8% of the administered caffeine dose was recovered in the urine in both groups. However, compared to the controls, the pregnant subjects produced smaller amounts of 1-methylxanthine and 1-methyluric acid, whereas the excretion of most of the other metabolites, particularly 3,7-dimethylxanthine and 3-methylxanthine tended to be greater.

Effects of transplantation and resection of a radiation-induced rat insulinoma on glucose homeostasis and the endocrine pancreas.

Twenty-one days after s.c. subscapular transplantation of a radiation-induced insulinoma, male NEDH rats exhibited hyperinsulinaemia and hypoglycaemia.

The psychopharmacological and electrophysiological effects of single doses of caffeine in healthy human subjects.

The effects of single doses of anhydrous caffeine (250 mg and 500 mg) and placebo on physiological, psychological measures and subjective feelings were studied in a double-blind, cross-over study in nine healthy subjects who had abstained from caffeine-containing beverages for 24 h before each occasion. Caffeine and caffeine metabolites in plasma and urine were assayed. Peak plasma concentrations were observed at 1 to 2 h with an approximate half-life of 5 h.

Potato steroidal alkaloids and neural tube defects: serum concentrations fail to demonstrate a causal relation.

Spoiled potatoes and, in particular, steroidal alkaloids have been proposed as an aetiological factor in the pathogenesis of neural tube defect (NTD). The present study involves the measurement of potato (solanum) steroidal alkaloid concentrations in serum by radioimmunoassay. Serum solanidine and total potato alkaloid concentrations were measured in two groups of women: one group pregnant with a fetus, subsequently shown to be affected by a NTD, the other with a healthy fetus.

The measurement of insulin-like growth factor I: clinical applications and significance.

Of the somatomedins so far measured, the selective quantitation of insulin-like growth factor I (IGF-I) appears to have the greatest potential in clinical diagnosis. There have been two approaches to the development of immunoassay systems. One type uses antibodies raised against synthetic fragments of IGF-I which exhibit cross-reactivity with the whole hormone.

The effects of sorbitol on the gastrointestinal microflora in rats.

The influence of dietary sorbitol on the quantity and quality of faecal microflora was studied in Wistar albino rats. The animals were gradually adapted to 20% dietary sorbitol or sucrose and faecal samples were analyzed for the numbers of major bacteria. No major changes in the numbers of total aerobic or anaerobic bacteria, aerobic streptococci and yeasts were observed after sorbitol feeding but sucrose appeared to decrease the total aerobes and anaerobes in the faeces.

Immunoreactive gastric inhibitory polypeptide and K cell hyperplasia in obese hyperglycaemic (ob/ob) mice fed high fat and high carbohydrate cafeteria diets.

The effect of diet composition on plasma and intestinal concentrations of immunoreactive gastric inhibitory polypeptide (GIP) and intestinal K cell density was examined in obese hyperglycaemic (ob/ob) mice. The mice were reared from 3 to 11 weeks of age on either stock diet, a high fat (HF) cafeteria diet or a high carbohydrate (HC) cafeteria diet. The HF cafeteria diet increased the concentration of GIP in plasma (75%) and in the intestine (118%) and increased the density (54%) of GIP-secreting K cells in the upper jejunum compared with the stock diet.

Insulin and C-peptide levels after oral and intravenous glucose. Contribution of enteroinsular axis to insulin secretion.

Peripheral venous plasma insulin and C-peptide concentrations were measured in 10 healthy volunteers, given either 100 g glucose orally or sufficient intravenous (i.v.) glucose to produce similar glucose concentrations when measured in arterialized blood.

The quantitative determination of 2'-deoxycytidine-5'-triphosphate in cell extracts by radioimmunoassay.

A radioimmunoassay (RIA) capable of quantitating dCTP in femtomolar amounts in cell extracts has been developed, and applied to human fibroblast cell lines and L5178Y mouse lymphoma lines. Cross reactivity of the antibody with CTP, though low (2.7%) has necessitated pre-RIA removal of CTP by either boronate affinity gel chromatography or sodium periodate oxidation.

Determination of the urinary metabolites of caffeine and theophylline by high-performance liquid chromatography. A comparative study of a direct injection and an ion-pair extraction procedure.

Chromatographic separation of methylxanthine metabolites was achieved using a Hypersil octadecylsilane column with a simple concave gradient elution programme of 0-12.75% acetonitrile in 1% tetrahydrofuran, pH 4.8, and the eluted components were detected by monitoring their absorption at 280 nm.

Specific binding of the C-peptide of proinsulin to cultured B-cells from a transplantable rat islet cell tumor.

Specific binding of the C-peptide of proinsulin was evaluated using a transplantable NEDH rat islet cell tumour predominantly composed of insulin-secreting B-cells. Cultured tumour B-cells exhibited greater than 90% viability assessed by trypan blue exclusion, and retained the ability to form tumours with accompanying hypoglycaemia and hyperinsulinaemia after reimplantation. During binding experiments with synthetic rat C-peptide I and iodinated tyrosylated rat C-peptide I, tumour B-cells exhibited 54 +/- 6% specific binding.

Differential insulin responses to oral and intravenous glucose in the transplantable rat insulinoma--a role for GIP.

We have previously demonstrated an impaired insulin response to intraperitoneal glucose and arginine by the transplantable NEDH rat insulinoma. The nature of this tumour B-cell defect has been further studied by investigating the response of insulinoma-bearing rats to intravenous and intragastric glucose. Intravenous glucose failed to stimulate plasma immunoreactive insulin (IRI) above high basal levels (14.