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Biomedical subjects

J D Baird

Publications and source records attributed to J D Baird.

At least 37 records · Page 2Linked to original sources
PubMed1993

Metabolic control in streptozotocin diabetic rats following transplantation of microencapsulated pancreatic islets.

Microencapsulated islet grafts implanted into the peritoneal cavity of a variety of animal models of diabetes have been shown to reverse hyperglycaemia over prolonged periods without immunosuppression. Here, effects of these grafts on intermediary metabolites, diurnal blood glucose and glycated haemoglobin were studied in streptozotocin-diabetic Wistar rats. Following transplantation (approximately 3000 islets) glucose and the ketone 3-hydroxybutyrate fell significantly (glucose: 19.1 +/- 0.6 (SD) to 9.2 +/- 4.3 mmol/l, p < 0.01; 3-hydroxybutyrate: 1.51 +/- 0.48 to 0.55 +/- 0.38 mmol/l, p < 0.02) and remained within/close to the normal range for at least four weeks. In control diabetic animals, values remained abnormally elevated. There was no difference in lactate, alanine or glycerol between the two groups. In transplanted animals there was a marked variation in blood glucose over a 24h period, values being low during daylight hours but with nocturnal peaks (up to 25 mmol/l) during the animals' normal feeding time. Glycated haemoglobin was also lower in transplanted animals but did not return to normal and the difference was not significant. In conclusion, microencapsulated islet grafts ameliorated the diabetic state. However, normal metabolic homeostasis was not achieved. The intraperitoneal site precludes direct graft vascular access and this may be a contributory factor. Additionally, daytime blood sugar values in murine models of diabetes may be a poor guide to graft function and glucose tolerance.

3-Hydroxybutyric Acid↗
PubMed1993

BB-DR/Edinburgh: a lymphopenic, non-diabetic subline of BB rats.

Diabetes-prone (DP) and diabetes-resistant (DR) sublines of the BB rat have been established in Edinburgh, U.K., separately from other existing colonies. In an examination of the lymphoid status of the two lines, BB-DP/Ed and BB-DR/Ed, it has been found that both lines have very low T-cell numbers, depressed B-lymphocyte numbers and a complete absence of peripheral CD8+ T cells, all features characteristic of the previously described genetic lymphopenia lesion. It was also noted that the peripheral T cells of both BB/Ed lines were larger than normal. The DP/Ed and DR/Ed lines were indistinguishable in all these respects, and furthermore, they were both shown to type as RT1u at the major histocompatibility complex (MHC). The genetic combination of lymphopenia and RT1u without expression of diabetes is not present in other extant BB lines and makes BB-DR/Ed a uniquely useful control strain for BB rat studies as well as a valuable genetic resource for the further genetic analysis of diabetes susceptibility in rats.

Animals↗
PubMed1992

Microencapsulated islet grafts in the BB/E rat: a possible role for cytokines in graft failure.

Alginate-polylysine microencapsulation has been proposed as a method of protecting transplanted pancreatic islets against immunological attack. Using this technique, prolonged graft survival has been reported in some diabetic animals. However, in the spontaneously diabetic insulin-dependent BB/E rat we found that intraperitoneal implantation of microencapsulated islets had only a short-lived effect on hyperglycaemia. Recovered microcapsules (both those implanted empty and containing islets) were surrounded by a foreign body type cellular overgrowth and, although many capsules remained intact, encapsulated islets were observed to be disintegrating. Loss of Beta cells was confirmed by immunohistology. Various polymer materials used in artificial membranes have been shown to activate macrophages involved in foreign body reactions and induce synthesis of interleukin-1 beta, a known Beta-cell toxin. Reduced secretion of insulin and progressive islet damage (indicated by a significant reduction in residual islet insulin and DNA content) were demonstrated when microencapsulated islets were incubated with interleukin-1 beta in vitro for 9 days. Similar effects were seen following exposure to a combination of gamma interferon and alpha tumour necrosis factor. Successful use of microencapsulation in islet transplantation depends upon the development of biocompatible membranes. The exclusion of smaller molecules, such as cytokines, which may be involved in foreign body mediated damage and microencapsulated islet graft rejection, could also be important.

Alginates↗
PubMed1992

Effects of hypoxia and azotaemia on the pharmacokinetics of amikacin in neonatal foals.

The effects of hypoxia and azotaemia on the pharmacokinetics of amikacin were evaluated in 20 full-term neonatal critically ill foals which required 24-h supportive care, antibiotics and dextrose-supplemented polyionic fluids given intravenously, nasal insufflation with oxygen and nutritional supplementation. There was no association between sepsis score or survival and pharmacokinetic parameters. Concurrent hypoxia and azotaemia were associated with significantly decreased clearance and increased peak and trough serum concentrations of amikacin; however, peaks or troughs did not exceed toxic values. Derangements in serum peak, trough and clearance values, which were present on admission, persisted over the 6-day duration of this study. Daily monitoring of serum amikacin concentration revealed a tendency to underdose (particularly in foals receiving aggressive fluid therapy), which necessitated increasing the dose/kg body weight (9-12 mg/kg) and increasing the dose interval (10-12 h) in 40% (8/20) of the cases, so that blood concentrations of amikacin could be maintained within the target range of 3-15 micrograms/ml. Amikacin-induced nephrotoxicity was not indicated by conventional laboratory testing, nor was it strongly suspected after examination of post mortem lesions.

Amikacin↗
PubMed1992

Mycoplasma felis pleuritis in two show-jumper horses.

Mycoplasma felis was identified as the cause of acute pleuritis in 2 show-jumping horses. The pleural exudate was proteinaceous, contained large numbers of neutrophils, and had a markedly increased lactate concentration. M. felis was isolated in pure culture from pleural fluid. Rising serum antibody titers to M. felis as well as a precipitous decline in titers to equine influenza virus were demonstrated in both horses. Pleural effusion in both horses and a pneumothorax detected in one of the horses resolved following a single drainage of pleural fluid and intravenous fluid, antibiotic, and analgesic therapy.

Animals↗
PubMed1991

The effect of diabetes on the in vivo acetylation capacity of the spontaneously diabetic, insulin-dependent BB/Edinburgh Wistar rat.

In contrast to previous studies using chemically-induced diabetic rats, the in vivo acetylation of sulphamethazine is increased in spontaneously diabetic, insulin-dependent BB/Edinburgh (BB/E) Wistar rats compared to non-diabetic control animals from the same colony. In both diabetic and non-diabetic rats, male animals had a significantly higher acetylation capacity than female animals. The percentage recovery of the administered dose was significantly higher in urine samples from female rats.

Acetylation↗
PubMed1991

The effects of renzapride, a novel prokinetic agent, in diabetic gastroparesis.

Gastric emptying was measured in 9 diabetic patients with autonomic neuropathy (Group 1) and 8 normal controls (Group 2) on 4 occasions after swallowing placebo, 0.5, 1.0 or 2.0 mg of the newly developed prokinetic drug renzapride given double-blind and in random order. The liquid component of the test meal was labelled with In113m and the solid with Tc99m. Liquid emptying was uni-exponential. Solid emptying comprised an initial lag phase, followed by a linear component. Following placebo, the mean lag phase of solid emptying was 40 +/- 7 (S.E.M.) min in Group 1 and 16 +/- 2 min in Group 2 (P less than 0.01). In Group 1 subjects renzapride reduced the mean lag phase by 20-26 min at all doses (P less than 0.01). No effect was seen in Group 2. The linear rate of solid emptying was similar in both groups (0.9 +/- 0.1 and 1.0 +/- 0.2%/min) and was not altered by renzapride. Mean liquid t1/2 was similar in Groups 1 and 2 after placebo (30 +/- 6 and 29 +/- 4 min, respectively) and was decreased with increasing doses of renzapride in both groups. No adverse effects were encountered in any subjects. Renzapride may be useful in the treatment of diabetic gastroparesis.

Adult↗
PubMed1991

Pulmonary structure and function in adult dairy cows with an expanded lung field.

Pulmonary function tests were performed on seven adult dairy cows with an expanded lung field (ExLF) and the results were compared to the values from seven cows with normal lung fields. The cows with ExLF had an increased functional residual capacity (FRC) and end-tidal N2 concentration of the final breath of the multiple-breath N2 washout (FETN2,fb), and an abnormal distribution of ventilation. The measurements of ventilation and gas exchange and pulmonary mechanics did not differ between the two groups. Postmortem examination of the lungs of five of the cows in each group indicated the cows with ExLF had a bronchiolitis with varying degrees of goblet cell hyperplasia, epithelial cell hyperplasia and metaplasia, smooth muscle hypertrophy, inflammatory cell infiltrate, vascular thickening, peribronchiolar fibrosis, and a mild overinflation of the lung. A histopathological score, based on the preceding indices and bronchus-associated lymphoid tissue, was correlated with FRC, FETN2,fb, the lung clearance index and pulmonary resistance. There were no correlations between the histopathological score and any of the measures of ventilation and gas exchange.

Animals↗
PubMed1991

Chronic copper poisoning in two Holstein cows.

Chronic copper poisoning with an acute hemolytic crisis is described in 2 mature Holstein dairy cows from separate herds. Toxic concentrations of copper were present in the serum and in liver and kidney tissues of each cow. There was no history of environmental or dietary exposure to excessive quantities of copper. No further clinical cases of chronic copper toxicosis were observed in the herds. As well as massive hemolysis, in both cows there was involvement of other organ systems including the liver and kidneys which contributed to the clinical course of the disease.

Animals↗
PubMed1990

HbA1 in assessment of metabolic control in diabetic BB/E rats.

Estimations of HbA1 levels have been used to assess long-term glycaemic control in spontaneously diabetic BB/E rats. The degree of metabolic control achieved by once daily insulin injections and continuous insulin infusion by osmotic minipump was compared. Citrate gel electrophoresis of lysed erythrocytes, previously washed and incubated in 0.9% NaCl, gave accurate HbA1 values without interference from either abnormal Hb variants or labile glycosylation products. Over a 12 week period there was no significant difference in the mean random weekly plasma glucose concentrations between diabetic rats maintained on insulin injections or continuous infusion therapy. The HbA1 values in the injection-treated animals remained unchanged throughout the study period (mean +/- SEM = 5.1 +/- 0.1%). Diabetic rats treated by osmotic minipump showed a steady decline in values over the same period (4.1 +/- 0.1%; p less than 0.001 vs injected rats) but levels remained higher than those recorded in non-diabetic control rats (2.9 +/- 0.01%; p less than 0.001 vs pump-treated rats). These differences in HbA1 were reflected in the plasma glucose values obtained during a 30 h glucose profile performed after six weeks of insulin therapy. Diabetic rats on injection therapy showed considerable diurnal variation in plasma glucose concentration (5.5-11.2 mmol/l; mean 8.9 +/- 0.5) but continuous insulin infusion eliminated the fluctuations giving a significantly lower mean glucose level over the 30 h period (7.3 +/- 0.1 mmol/l; p less than 0.005). HbA1 levels show a poor correlation with random plasma glucose estimations (r = 0.43) but provide a simple and accurate assessment of long-term glycaemic control without the need for multiple 24 h glucose profiles.

Animals↗
PubMed1990

Insulin-mimicking anti-idiotypic antibodies in development of spontaneous autoimmune diabetes in BB/E rats.

BB/E rats spontaneously develop a form of autoimmune diabetes resembling insulin-dependent diabetes mellitus (IDDM) in humans. IDDM results from central destruction of the insulin-producing beta-cells of the pancreatic islets. Herein, we report that the outbreak of IDDM in BB/E rats is preceded by the spontaneous development of an anti-idiotypic antibody to a particular antibody to insulin made by the rats. This anti-idiotype, designated anti-DM-id, behaves as an antibody to the insulin-hormone receptor. Thus, a spontaneous anti-idiotypic antibody network whose products can affect the peripheral utilization of insulin seems to accompany the central destruction of beta-cells in developing IDDM.

Animals↗
PubMed1990

Effect of cyclosporin on pancreatic events and development of diabetes in BB/Edinburgh rats.

The effect of cyclosporin administered from 30 to 100 days of age on pancreatic events and the development of insulin-dependent diabetes has been studied by serial pancreatic biopsy of individual diabetes-prone BB/Edinburgh rats. Cyclosporin completely prevented the development of diabetes up to 150 days of age and reduced the incidence to 50% of controls at 452 days of age. Islet cell surface antibodies paralleled the development of diabetes. Insulin autoantibodies were unrelated to diabetes and not affected by cyclosporin. Immunohistochemical analysis of pancreatic biopsies from untreated control diabetes-prone rats with monoclonal antibodies specific for rat MHC molecules and T- and B-lymphocyte and macrophage subsets showed that the first abnormality seen in rats that subsequently developed diabetes was hyperexpression of MHC class I molecules on vascular endothelium and islet cells. This was followed by accumulation of ED1+ macrophages at perivascular and periductal sites adjacent to noninfiltrated islets. Increased expression of MHC class II molecules on vascular endothelial cells was also noted. Most cells infiltrating the islets initially were also ED1+ macrophages, followed by increasing numbers of other activated effector cells including helper and cytotoxic-suppressor T lymphocytes and natural killer cells. Obliteration of insulin-containing cells was associated with regression of the infiltrate. Treatment with cyclosporin had no effect on pancreatic hyperexpression of MHC class I molecules but markedly inhibited accumulation of ED1+ cells at extraislet sites, the subsequent recruitment of immune effector cells, and islet infiltration. This resulted in a delay of the onset of diabetes in some rats and prevention of diabetes in others.

Animals↗
PubMed1989

Timed interruption of insulin therapy in diabetic BB/E rat pregnancy: effect on maternal metabolism and fetal outcome.

Experimental and clinical studies have suggested that periods of poor metabolic control in early diabetic pregnancy have an adverse effect on the developing embryo, but the precise nature and mechanism of this damaging influence have not been defined. In this study the effect of withdrawing treatment with insulin for 2 days at various times during early gestation on maternal metabolism and fetal outcome has been investigated in the spontaneously diabetic BB/E rat. Non-diabetic BB/E rats and diabetic BB/E rats treated continuously with insulin throughout pregnancy served as controls. Continuously treated diabetic rats had a higher rate of fetal resorption and bigger placentae and their offspring had fewer ossification centres, lower extractable pancreatic insulin content, larger hearts, and smaller kidneys and lungs than the offspring of non-diabetic rats. Interruption of treatment with insulin further aggravated the adverse effect of diabetes on the outcome of pregnancy by resulting in a further increase in the rate of fetal resorption, a rise in the neonatal death rate, a reduction in fetal body weight, and retardation of skeletal development. These effects were more apparent when interruption of treatment with insulin occurred during the period of organogenesis, i.e. during gestational days 8 and 9, and 10 and 11. Two severe malformations were seen, both in litters originating from mothers whose treatment with insulin was interrupted during and immediately before fetal organogenesis. We conclude that a period of disturbed maternal metabolism during fetal organogenesis is capable of affecting the survival, growth, and organ development of the fetus and that the spontaneously diabetic insulin-dependent BB rat appears to be a good model for studies of the effect of diabetes and its treatment on the outcome of pregnancy.

Animals↗
PubMed1988

Folic acid therapy for alopecia in a Charolais calf.

A three-week old male Charolais calf which had a history of progressive hair loss and clinical signs, including crusts and brown patches similar to those in folic acid deficiency syndrome in man, was subjected to folic acid therapy. Daily oral administration of folic acid (1 mg/kg/day) resulted in the gradual disappearance of the crusts and patches within two weeks and a steady growth of hair and recovery to a normal state within two months. Folic acid, which is required for cellular turnover in a variety of tissues and organs including the hair follicle, may serve as an effective therapeutic agent in some types of alopecia triggered by a deficiency of either folic acid or the co-enzymes involved in the synthetic pathway of DNA.

Alopecia↗
PubMed1988

Interferon-gamma induces class II MHC antigens on RINm5F cells.

The ability of recombinant interferon-gamma (rIFN-gamma) to induce major histocompatibility complex (MHC) antigen expression in the rat insulinoma cell line RINm5F was investigated. The cells were stained with monoclonal antibodies specific for rat class I and class II MHC antigens. RINm5F cells endogenously expressed class I antigens; this was enhanced by rIFN-gamma. Class II antigens could not be detected on RINm5F cells, but both I-A and I-E were induced by rIFN-gamma.

Adenoma, Islet Cell↗
PubMed1988

Distinct macrophage subpopulations in pancreas of prediabetic BB/E rats. Possible role for macrophages in pathogenesis of IDDM.

Use of monoclonal antibodies directed against rat macrophages and serial pancreatic biopsy in the prediabetic period have enabled us to document the involvement of macrophages in the pancreatic events leading to onset of diabetes in the spontaneously diabetic BB/E rat. A few weeks before onset of disease, there is marked recruitment and accumulation of ED1+ macrophages at periductal and perivascular locations adjacent to noninfiltrated islets. These recruited cells, distinct from the resident ED2+ tissue macrophages, then infiltrate the islets. Infiltration of the pancreas by ED1+ macrophages is therefore a very early event in the prediabetic period and suggests a possible role for macrophages in the pathogenesis of insulin-dependent diabetes mellitus (IDDM) in this animal model.

Animals↗