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Biomedical subjects

R H Smith

Publications and source records attributed to R H Smith.

At least 109 records · Page 6Linked to original sources
PubMed1985

Mebendazole and insulin secretion from isolated rat islets.

In a preliminary communication we reported that mebendazole, a vermicide, decreased plasma glucose and free fatty acid concentrations and increased plasma C peptide concentrations in both type II diabetic patients. Therefore, we suggested that mebendazole was an insulin secretagogue. However, these were uncontrolled studies, and improved metabolic control in these patients due to spontaneous remission rather than drug-induced insulin secretion was a possibility. To investigate the direct effect of mebendazole on insulin secretion we used intact islets isolated from normal rat pancreata. Mebendazole in concentrations as low as 10 to 20 mumol/L caused a twofold to threefold increase in acute-phase insulin release from isolated perifused rat islets. This heightened insulin release occurred in the presence of glucose-stimulated insulin secretion.

Animals↗
PubMed1985

Lack of biochemical polymorphism in British fallow deer.

Seven-hundred and ninety-four samples of fallow deer (Dama dama L.) blood or tissue were collected from 37 sites in England and Wales. A selection of these samples was screened for electrophoretic variation at each of 30 loci (minimum of 88 samples per locus). No genetic variation was found. Possible explanations for the lack of polymorphism are discussed. It is suggested that European fallow deer experienced a genetic bottleneck during a period of captivity in Mesolithic or Neolithic times.

Animals↗
PubMed1985

Physiological changes in cultured sorghum cells in response to induced water stress : I. Free proline.

Ten varieties of Sorghum bicolor (L.) Moench were grown as callus cultures under conditions of water stress, which was induced by addition of polyethylene glycol (molecular weight 8000) in the medium. Growth and free proline were estimated in the control and water-stressed cultures. In all varieties, proline levels were low in the absence of water stress and the levels increased in response to water stress. However, the magnitude of these increases were not correlated with stress tolerance of the individual varieties in culture. Thus increase in proline seems to be an incidental consequence of stress in vitro and not an adaptive response to combat water stress in sorghum.

Journal Article↗
PubMed1984

Improvement of metabolic control in diabetic patients during mebendazole administration: preliminary studies.

After the observation of decreasing insulin resistance in a diabetic patient during treatment with mebendazole for nematosis, we investigated the effect of mebendazole on metabolic control in six Type 1 (insulin-dependent) and six Type 2 (non-insulin-dependent) diabetic patients, eight of whom were chronically resistant to conventional treatment. Before and after mebendazole treatment for 1 month, plasma glucose and serum C-peptide concentrations were determined both fasting and 4 h after a mixed breakfast. Improvements in fasting blood glucose concentrations occurred in Type 1 (12.83 +/- 1.11 versus 6.56 +/- 0.56 mmol/l; p less than 0.05) and Type 2 (10.22 +/- 0.56 versus 7.56 +/- 0.67 mmol/l; p less than 0.05) diabetic patients and were associated with increases in post-cibal C-peptide responses in Type 1 and Type 2 diabetic patients. Following discontinuation of mebendazole, metabolic control deteriorated in five out of the six Type 1 diabetic patients and in all the Type 2 diabetic patients. We conclude that mebendazole increases insulin secretion, and decreases plasma glucose concentration in Type 1 and Type 2 diabetic patients. However, these beneficial effects may be transient.

Adult↗
PubMed1984

Induction of delayed-type hypersensitivity to measles virus in mice.

Intracutaneous injection of inactivated measles virus (MV) into hind footpads of BALB/c mice infected 5 to 11 days previously with MV produces a strong delayed-type hypersensitivity (DTH) response. Pretreatment of mice with cyclophosphamide (CP) results in a significantly stronger response. In CP-pretreated mice, the optimal infecting dose of live MV and the restimulating amount of inactivated MV are approximately 10(7) plaque-forming units and 2 micrograms/mouse, respectively. The optimal time after infection for measuring DTH to MV is 7 days, while the optimal CP-pretreatment concentration is 200 mg/kg. The DTH response generated by MV is specific and not caused by fetal calf serum or Vero cell antigens. MV DTH is transferable to uninfected mice with lymph node cells. Transfer of DTH is sensitive to treatment with anti-Thy 1.2 serum plus complement, indicating the response is T cell dependent. With this sensitive assay for measuring cell-mediated immunity to MV, it will now be possible to analyze T cell cross-reactivity among paramyxoviruses and assess viral cell-mediated immunity in mice infected with neuroadapted MV.

Animals↗
PubMed1984

The efficiency of microbial protein synthesis in the rumen and the degradability of feed nitrogen between the mouth and abomasum in steers given different diets.

Protozoa-free steers with simple rumen and abomasal cannulas were given basal diets consisting of a concentrate mixture of flaked maize and tapioca with barley straw (BS) or alkali-treated barley straw (BSA). Other diets were supplemented with urea (BSU and BSAU respectively) or with fish meal replacing the tapioca (BSF and BSAF respectively). The diets were isoenergetic and calculated to provide sufficient metabolizable energy (ME) to support a growth rate of 0.5 kg/d. Rumen-degradable nitrogen (RDN):ME values (g/MJ) were estimated to be 0.50, 1.20 and 0.80 for the basal diet, urea- and fish-meal-supplemented diets respectively. RNA and alpha,epsilon-diaminopimelic acid (DAP) were used as microbial markers. 103Ruthenium and polyethylene glycol (PEG) were given as flow markers and flows (g/24 h) at the abomasum of organic matter (OM) and nitrogenous constituents were calculated. Samples of mixed bacteria separated from rumen digesta from animals receiving N-supplemented diets contained significantly more N than those from animals receiving basal diets (approximately 74 and 62 mg/g dry matter (DM) respectively) but there were no other significant differences in total-N contents between treatments. RNA-N:total-N values were similar for all diets (approximately 0.13). DAP-N:total-N values were significantly lower in bacteria from animals receiving alkali-treated (AT) rather than untreated (UT) straw (approximately 0.008 and 0.011 respectively). The proportion of OM intake digested in the rumen (ADOM) was significantly higher for animals receiving AT straw rather than UT straw (approximately 0.54 and 0.43 respectively). N supplementation had no effect on OM digestibility.(ABSTRACT TRUNCATED AT 250 WORDS)

Abomasum↗
PubMed1984

Protein utilization in the young steer: digestion and nitrogen retention of 15N-labelled rumen bacterial protein.

15N-labelled mixed rumen bacteria, obtained from a steer that had received [15N]urea in its diet, were disrupted ultrasonically and freed from nucleic acids and their degradation products. Samples were subjected to a simulated abomasal digestion with pepsin. The digests were infused with a non-absorbable marker (polyethylene glycol) into the duodenum of four steers equipped with simple duodenal and re-entrant ileal cannulas and adapted to a diet of barley straw, flaked maize and urea. The outflow from the ileum was collected for 6-7 h. The mean value for the digestibility of 15N bacterial proteins in the small intestine was estimated to be 0.74. [14C]urea was administered intravenously during the infusion of the 15N-labelled protein into the duodenum. Urine and faeces were collected for the next 48 h and the proportion of urea-N produced, that was excreted in the urine, estimated from urine 14C excretion. Total urea 15N production was estimated from this value and the amount of 15N excreted in the urine. The mean proportion of 15N absorbed that was deposited in body protein, 0.70, was calculated by difference. The over-all efficiency of utilization of 15N in the infused rumen bacterial protein was 0.52. An approximate estimate of the mean rate of protein synthesis calculated from the data was 24 g/kg body-weight (W)0.75 per d and compared with an estimated net deposition of protein of 1.67 g/kg (W)0.75 per d. The importance of these values in factorial schemes for estimating ruminant N requirements is discussed.

Animals↗
PubMed1983

The influence of changes in tension on protein synthesis and prostaglandin release in isolated rabbit muscles.

Intermittent stretching of isolated rabbit muscles increased the rate of protein synthesis by 70% and prostaglandin-F2 alpha release by 105%. Both effects of intermittent stretching were blocked by indomethacin and meclofenamate; the absence of Ca2+ together with added EGTA also inhibited both processes. The residual influence of intermittent stretching on protein synthesis was closely correlated with prostaglandin-F2 alpha release, which may be the link between mechanical activity and protein synthesis in skeletal muscle.

Animals↗
PubMed1983

Protein synthesis in isolated rabbit forelimb muscles. The possible role of metabolites of arachidonic acid in the response to intermittent stretching.

Protein synthesis was measured in isolated intact rabbit muscles by the incorporation of [3H]phenylalanine added at a high concentration (2.5 mM) to the incubation medium. Intermittent mechanical stretching substantially increased the rate of protein synthesis relative to that in control muscles incubated under a constant tension. Indomethacin and meclofenamic acid, inhibitors of the enzyme cyclo-oxygenase, which converts free arachidonic acid into the prostaglandins, prostacyclins and thromboxanes, decreased the rate of protein synthesis in intermittently stretched muscles, but had no effect on synthesis rates in the unstimulated controls. Arachidonic acid at concentrations of 0.2 and 1.0 microM gave a highly significant increase in the rate of protein synthesis in muscles incubated under a constant tension. The ability of arachidonic acid to increase protein-synthesis rates was abolished by the addition of indomethacin. Activation of protein synthesis by intermittent stretching persisted for 10-20 min after the stretch stimulation had ceased. Indomethacin, added either during the initial incubation with intermittent stretching or during the subsequent period when protein synthesis was measured after stimulation had ceased, decreased protein-synthesis rates. This decrease was similar whether indomethacin was present during the initial, final or entire incubation period. In experiments analogous with those in (4) above, when Ca2+ was withheld and EGTA added for the entire incubation, rates of protein synthesis were again decreased. The rates of protein synthesis observed when Ca2+ was present during either an initial stimulation phase or a final, unstimulated, measurement phase were similar, and were intermediate between control rates and those in muscles incubated without Ca2+ for the whole experiment. Two prostaglandins, F2 alpha (2.8 microM) and A1 (28 microM), increased rates of protein synthesis in unstimulated muscles, but prostaglandins E2 and D2 and the leukotrienes C4 and D4 failed to do so. It is concluded that the stretch-stimulated increase in protein synthesis may be caused by activation of membrane phospholipases, release of arachidonic acid and a consequent increase in prostaglandin synthesis.

Animals↗
PubMed1983

Factors affecting the capture of dietary nitrogen by micro-organisms in the forestomachs of the young steer. Experiments with [15N]urea.

For a period of at least 2 weeks before an experimental collection each of four young steers received total daily intakes consisting of approximately (g/kg) 600 straw and 400 concentrates with the nitrogen provided mainly as urea and in which the main energy source was starch (tapioca) for diet 1 and glucose for diet 2. Concentrates were given twice daily at about 09.00 and 17.00 hours, straw at 17.00 hours only. The value for the ratio, rumen-degradable N: metabolisable energy (g/MJ) in the daily intake was estimated to be approximately 1.2. On the day that an experimental collection was to be made the urea normally given in the feed at 09.00 hours was labelled with 15N. This urea and sometimes the appropriate energy source were added either as a single dose (SD) at 09.00 hours or in three equally-divided doses (DD) at 09.00, 11.00 and 13.00 hours. Treatments, given in a Latin-square design, were: (A), starch (SD) + urea (SD); (B), starch (SD) + urea (DD); (C), glucose (SD) + urea (DD); (D), glucose (DD) + urea (DD). Doses of polyethylene glycol (PEG) and 144Ce (as cerous chloride) were given as markers with the urea. After these doses were given, samples of abomasal and duodenal digesta were taken periodically for 72 h. It appeared that virtually all the PEG had left the rumen by this time and mean recovery of 144Ce relative to PEG was approximately 90%. From recoveries of non-ammonia-15N (microbial 15N) at the abomasum, estimated relative to PEG, values for mean fractional efficiencies of conversion of urea-N to microbial-N were calculated to be 0.59, 0.59, 0.40 and 0.41 for treatments A, B, C and D respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Abomasum↗
PubMed1983

Factors influencing the digestion of dietary carbohydrates between the mouth and abomasum of steers.

Six protozoa-free steers with simple rumen and abomasal cannulas were given basal diets consisting of a concentrate mixture of flaked maize and tapioca with either barley straw (BS) or alkali-treated barley straw (BSA). Other diets used were supplemented with urea (BSU and BSAU respectively) or contained fish meal in place of tapioca BSF and BSAF respectively). The diets were given in a 6 X 6 Latin square design. Diets were isoenergetic and provided sufficient metabolizable energy (ME) to support a growth rate of approximately 0.5 kg/d. Basal diets, urea- and fish-meal-supplemented diets had estimated rumen-degradable nitrogen (RDN):ME values (g/MJ) of 0.5, 1.2 and 0.8 respectively. 103Ruthenium and polyethylene glycol were given as flow markers, and flows (g/24 h) at the abomasum of organic matter (OM) and carbohydrate components were calculated. True digestibility coefficients of OM between mouth and abomasum were significantly greater for diets containing alkali-treated straw (approximately 0.63) than for those containing untreated straw (approximately 0.55) but were not significantly affected by N supplementation. Digestibility coefficients of the neutral-sugar components of dietary polysaccharides between mouth and abomasum were 0.28, 0.34, 0.31, 0.23, 0.31 and 0.87 for mannose, galactose arabinose, xylose, cellulose-glucose and starch-glucose respectively for diet BS. Corresponding values were 0.37, 0.42, 0.56, 0.51, 0.40 and 0.88 for diet BSA. All but the mannose and starch-glucose values were significantly greater for the latter diet. N supplementation also led to increases in digestibility of all neutral sugars except mannose and starch-glucose. Fish meal produced a markedly greater effect than urea but only significantly so for cellulose-glucose. Thus, the highest digestibilities were seen for diet BSAF and were 0.68, 0.67, 0.74 and 0.64 for galactose, arabinose, xylose and cellulose-glucose respectively. Of all these sugars xylose consistently showed the greatest response in digestibility to sodium hydroxide treatment or N supplementation.

Abomasum↗
PubMed1983

Incorporation of nitrogen into rumen bacterial fractions of steers given protein- and urea-containing diets. Ammonia assimilation into intracellular bacterial amino acids.

Experiments were carried out in vivo to investigate the pathways of ammonia incorporation into rumen bacteria, bacterial fractions and free amino acids within the bacteria. Steers were alternately given two isoenergetic, isonitrogenous diets containing the nitrogen mainly as either urea or decorticated groundnut meal (DCGM). At the end of each period on a given diet, a solution of 15NH4Cl was infused into the rumen and samples of rumen contents were removed at 2, 10, 20 and 90 min and 5, 10 and 24 h afterwards. Concentrations of ammonia and its 15N enrichment were determined and samples of mixed rumen bacteria were prepared. Bacteria were disrupted ultrasonically and separated into bacterial protein, cell wall and protein-free cell supernatant fractions. Amino acids were separated after hydrolysis and their 15N contents determined. A rumen fluid circulation pump was developed so that representative samples could be taken at very short time intervals after the introduction of the 15N label. Rumen pH changes, rumen fluid dilution rates and patterns of rumen ammonia concentrations were consistent with normal rumen metabolism. Net bacterial synthesis (as calculated from the net outflow of bacteria from the rumen) was significantly (P less than 0.05) greater with the DCGM diet (12.4 g bacterial N/d) than with the urea diet (9.24 g bacterial N/d). With both diets the 15N label rapidly left the rumen ammonia pool and entered the rumen bacteria. Analysis of the bacterial fractions indicated that the label appeared rapidly in the protein-free cell supernatant fraction and more slowly in the bacterial protein and cell wall fractions. With the DCGM diet bacteria apparently utilized intracellular label less efficiently than with the urea diet. The proportion of N in the protein-free cell supernatant was higher with the DCGM diet, suggesting increased levels of intracellular amino acids and peptides, following extracellular protein degradation. Levels of enrichment of the amino acids alanine and glutamate in the protein-free cell supernatant fraction suggested that the enzymes alanine dehydrogenase (EC 1.4.1.1) and glutamate dehydrogenase (EC 1.4.1.2 and 1.4.1.4) may be the major enzymes for assimilating ammonia when concentrations of soluble carbohydrate and rumen ammonia are high in the rumen. The high levels of intracellular alanine are discussed with reference to published work on the excretion of alanine by rumen bacteria.

Amino Acids↗