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Biomedical subjects

M Gill

Publications and source records attributed to M Gill.

At least 181 records · Page 10Linked to original sources

Nutritional and endocrinological manipulation of lean deposition in forage-fed steers.

The effect of supplementing grass silage with fishmeal on growth, muscle composition and the rate of muscle protein synthesis was investigated in young Friesian steers with and without oestradiol implants. The effect of the beta-adrenergic agonist cimaterol was simultaneously investigated in animals fed on silage alone. Treatments lasted for 9 or 10 weeks. Fishmeal supplementation significantly increased animal growth rates (P less than 0.001) and the weights of three dissected muscles (P less than 0.001) compared with the silage-fed controls. These effects were further enhanced in animals also implanted with oestradiol. Muscle weights expressed as a proportion of body-weight were increased by fishmeal, suggesting that protein deposition had been enhanced. No further increase in the proportional muscle weights was obtained with oestradiol. Muscle dry matter content tended to be increased in both implanted and non-implanted animals receiving fishmeal compared with controls, but the proportions of protein, fat and ash were relatively constant. The intramuscular lipid composition was slightly altered by fishmeal. Muscle protein fractional synthetic rates (FSR), measured by continuous infusion of [3H]tyrosine, were increased by fishmeal in all three muscles of both implanted and non-implanted animals. There were no differences, however, due to oestradiol, over non-implanted fishmeal animals. This suggests that oestradiol may increase muscle accretion by reducing protein degradation rate. Cimaterol significantly increased longissimus dorsi (P less than 0.05) and vastus lateralis (P less than 0.01) muscle weights but had no effect on semitendinosus muscle weight or live-weight gain. The proportion of protein was increased (P less than 0.001) and the fat content reduced (P less than 0.05) in all three muscles but intramuscular lipid composition was not markedly affected. Whilst methylhistidine: creatinine excretion was reduced by cimaterol, FSR were increased in the l. dorsi and v. lateralis muscles suggesting beta-agonists have effects on both protein synthesis and protein degradation.

Adrenergic beta-Agonists↗

Effect of H2-receptor antagonists, cimetidine and ranitidine on reproductive functions in male mice.

Na+,K(+)-ATPase and Ca(2+)-ATPase in testis were inhibited with an oral administration of cimetidine and ranitidine. Cimetidine at dose level of 100 and 30 mg while ranitidine at 70 and 10 mg per kg body wt inhibited the enzyme activities, 24 hr after single administration or daily administration for 15-days. Mg(2+)-ATPase activity was increased with cimetidine while ranitidine inhibited the enzyme. Michaelis-Menten kinetic characteristics revealed mixed type of inhibition for Na+,K(+)-ATPase with cimetidine, whereas it was noncompetitive for Ca(2+)-ATPase with cimetidine as well as ranitidine administration. Inhibition of Na+,K(+)-ATPase with ranitidine was also of noncompetitive type. Mg(2+)-ATPase behaved differently with administration of ranitidine at both the time points used i.e. noncompetitive type of inhibition after 24 hr and mixed type after 15-days. Histologically, signs of degeneration of testicular elements appeared after administration of cimetidine with a significant decrease in tubular diameter and germinal epithelial cell height. Ranitidine administration did not produce any change in the seminiferous tubules of testis. Scanning electron microscopy of spermatozoa from cimetidine-treated mice exhibited distinct departure from the normal morphology such as, (i) breaks at various places along distal portion of the tail, (ii) roughening, wrinkling and disorganization of plasma membrane of the head region, (iii) decapitation of the head and (iv) changes in shape of cytoplasmic droplet. Ranitidine administration showed normal morphology of the spermatozoa.

Administration, Oral↗

Interaction of H2-receptor antagonists, cimetidine and ranitidine with microsomal drug metabolizing and other systems in liver.

Cimetidine has been demonstrated to impair microsomal oxidative drug metabolizing and other enzyme systems in mouse liver. The inhibition is rapid, occurring after a single administration and also found to be dose-dependent. It is more significant after daily administration for 15 days. Enzyme inhibition by ranitidine, another H2-receptor antagonist was comparatively less at all the concentrations of the drug tested. An increased activity of alkaline phosphatase, glutamate-pyruvate and glutamate-oxaloacetate transaminase was observed in liver with cimetidine administration, whereas that of lactate and succinate dehydrogenase was inhibited only after administration of 2000 mg cimetidine per kg body weight. Except alkaline phosphatase other enzymes were unaffected after ranitidine administration. Analysis of lipid classes in liver showed that phospholipid, triglycerides and free fatty acid contents were significantly decreased in drug administration while cholesterol level showed very little or no change. Microsomal and soluble protein contents were significantly increased which probably indicate that the inhibition in the enzyme activity by histamine H2-receptor antagonists may be a lipid mediated process and not resulted from the reduced availability of the enzyme protein.

Animals↗

On the two-compartment model for estimating the rate and extent of feed degradation in the rumen.

An analysis of the compartmental scheme used to determine the rate and extent of ruminal degradation of feeds is presented. Attention is given to the kinetic representation of the degradation of the potentially degradable fraction. Changing the kinetic order of the rate, and introducing indigestible substrate inhibition and microbial activity into its representation, are investigated. This leads to response functions such as the Gompertz and logistic for describing the cumulative disappearance of potentially degradable substrate during in-sacco and in-vitro incubation.

Animals↗

Nosocomial sepsis associated with interleukin-2.

STUDY OBJECTIVE: To determine the incidence, clinical magnitude, and risk factors for nosocomial bacteremia in patients given interleukin-2 with or without (+/-) lymphokine activated killer (LAK) cells for cancer immunotherapy. DESIGN: Cohort study. SETTING: Clinical study unit of tertiary medical center. PATIENTS: All patients entering the interleukin-2 +/- LAK cancer immunotherapy protocol during a 28-month period. Control groups were patients in a surgical intensive care unit, patients receiving total parenteral nutrition, and patients with solid tumors. MEASUREMENTS AND MAIN RESULTS: Twenty of 107 (19%) interleukin-2-treated patients developed sepsis; in 12 of these patients, sepsis was intravenous catheter-associated. The bacteremia rate among patients receiving total parenteral nutrition, in the surgical intensive care unit, or having solid tumors was 2.8%, 4.1%, and 1.9%, respectively. Staphylococcus aureus was the pathogen in 13 courses; Staphylococcus epidermidis, in 5; and Escherichia coli, in 2. Two patients died; three developed suppurative thrombophlebitis; one developed septic arthritis; one, septic arterial aneurysm; and one, peritonitis with probable meningitis. Colonization with S. aureus increased the risk of S. aureus bacteremia 6.3-fold (95% CI, 2.8 to 14.5; P less than 0.001); skin desquamation at the catheter site increased the relative risk 2.0-fold (95% CI, 1.3 to 3.1; P = 0.031). Both colonization with S. aureus and skin desquamation increased the relative risk of S. aureus bacteremia 14.5-fold (95% CI, 4.1 to 50.9; P less than 0.0001). CONCLUSIONS: Staphylococcal bacteremia is more frequent in patients receiving interleukin-2 therapy and is associated with substantial morbidity and toxic skin reactions.

Adult↗

Effect of histamine H2-receptor antagonist, ranitidine on renal brush border and basolateral membranes.

The antiulcerogenic drug ranitidine, given orally to mice, brought about reductions of kidney-bound hydrolytic enzymes at three different dose levels, viz. 10 mg, 100 mg, and 1000 mg/kg body weight, and for three different time points (single administration for 2 h and 24 h, and daily administration for 15 days). The activities of Na+, K(+)-ATPase, Ca2(+)-ATPase, and Mg2(+)-ATPase (marker enzymes of basolateral membranes) were reduced, and these reductions were significant at higher doses and after a 24-h single treatment or 15 days' daily treatment. Maltase, alkaline phosphatase, and leucine aminopeptidase (marker enzymes of brush border membrane [BBM]) activities were significantly inhibited after ranitidine treatment. Kinetic analysis of BBM-associated enzymes indicated that ranitidine decreased the maximum of apparent initial enzyme velocity (Vmax) of maltase, alkaline phosphatase, and leucine aminopeptidase. The substrate affinity constant (Km) was decreased in the case of alkaline phosphatase and maltase, while it was not altered in the case of leucine aminopeptidase. In vitro addition of ranitidine to renal BBM also produced significant inhibition of these enzymes, the inhibition constants (Ki) for maltase, alkaline phosphatase, and leucine aminopeptidase being 7.5, 15.5, and 3.5 mM, respectively. Membrane-bound lipid estimation showed a significant increase in phospholipids, triglycerides, and free fatty acids. Cholesterol, however, was decreased in both renal basolateral and brush border membranes.

Alkaline Phosphatase↗

The effect of fishmeal supplementation of a straw-based diet on growth and calorimetric efficiency of growth in heifers.

Thirty-two 160 kg dairy heifers were used to measure the effects of increasing dietary protein content on growth and heat production. A basal diet containing (g/kg) 550 sodium hydroxide-treated straw, 220 barley, 220 sugarbeet pulp and 10 urea was offered with 0, 76 and 152 g fishmeal/kg dry matter of the basal diet (F0, F1 and F2 levels respectively). The three diets were each given at two levels of feeding (low, L; high, H): 57.6 g/d per kg metabolic body-weight (W0.75) for the LFO diet and 74.7 g/d per kg W0.75 for the HFO diet. Apparent digestibility of the diets increased in response to the addition of fishmeal. Mean dry matter digestibility values were 0.67, 0.67, 0.69, 0.66, 0.68 and 0.69 and those for acid-detergent fibre digestibility were 0.60, 0.63, 0.66, 0.58, 0.60 and 0.65 for diets LF0, LF1, LF2, HF0, HF1 and HF2 respectively. Nitrogen retention increased in response to both fishmeal and feeding level. Live-weight gains were 170, 296, 434 g/d for the LF0, LF1 and LF2 diets and 468, 651 and 710 g/d for the HF0, HF1 and HF2 diets respectively. There were significant effects of increasing the plane of feeding and the level of fishmeal in the diet on live-weight gain. Dietary effects on live-weight gains were accompanied by increases in mean energy retention of 23, 45, 82, 94, 160 and 152 kJ/d per kg W0.75 for diets LF0, LF1, LF2, HF0, HF1 and HF2 respectively, but no definite evidence was obtained that dietary supplementation with fishmeal modified the efficiency of utilization of metabolizable energy for growth.

Animal Feed↗

The effect of fishmeal on the digestion of grass silage by growing cattle.

The effect of two levels of fishmeal substitution (50 (FM1) and 150 (FM2) g/kg) of a grass silage control diet (C) on the rumen digestion of organic matter and nitrogen, and the small intestinal disappearance of amino acids was examined in young growing cattle each equipped with simple PVC cannulas in the dorsal sac of the reticulo-rumen, the proximal duodenum and the terminal ileum. The silage was a primary growth of perennial ryegrass (Lolium perenne) (+formic acid) with a total N content of 22 g/kg dry matter (DM) (diet C). Fishmeal substitution increased this to 26 (diet FM1) and 34 (diet FM2) g/kg DM. On diets C and FM1, approximately 0.71 of digestible organic matter intake was apparently digested in the rumen, but this was significantly (P less than 0.05) reduced on diet FM2 (0.60). Whilst duodenal flows of non-ammonia N and total amino acids were significantly (P less than 0.01) increased at the highest level of fishmeal inclusion only, the synthesis of microbial N was significantly (P less than 0.001) reduced by fishmeal inclusion, and feed N degradability declined progressively in response to increased fishmeal. Both levels of fishmeal addition caused a significant (P less than 0.05) reduction in the fractional outflow rate of water from the rumen, and on the highest level of fishmeal significant (P less than 0.05) increases in rumen ammonia concentration and rumen propionate molar proportions were observed. The net effect of the highest level of fishmeal substitution was to increase amino acid absorption from the small intestine by 0.47 compared with the control diet (P less than 0.05), but due to an elevated ileal flow of amino acid no such effect was detected at the lowest level of fishmeal substitution. Composition of the absorbed amino acid fraction was relatively unaffected by the treatments imposed, despite large changes in the composition of the duodenal protein. The apparent non-linearity of response to fishmeal substitution is discussed and the amino acid supply findings are compared with the protein retention findings obtained in an earlier study by Gill et al. (1987). By two methods of calculation it was estimated that the amino acid N fraction disappearing from the small intestine was utilized with an efficiency of between 0.51 and 0.53 and no apparent effects due to diet or level of amino acid supply were detected.

Amino Acids↗

Enumeration of anaerobic chytridiomycetes as thallus-forming units: novel method for quantification of fibrolytic fungal populations from the digestive tract ecosystem.

An endpoint dilution procedure, based on the technique of most probable numbers, was developed to enumerate anaerobic chytridiomycetes as thallus-forming units. The method does not distinguish between zoospores and thalli, but does permit enumeration of fungal populations with respect to their ability to digest plant cell walls. Fibrolytic populations in batch culture, ruminal contents, and feces were compared by relating viable counts to the dry matter content of enumerated samples (i.e., thallus-forming units per gram of dry matter). Batch cultures of Neocallimastix sp. strain R1 grown on wheat straw were used to assess the enumeration procedure and to demonstrate the potential of the technique for quantification of anaerobic fungi in vivo. Determination of total ruminal contents from steers enabled the quantification of the entire population of fiber-degrading anaerobic fungi in the reticulorumen. The enumeration procedure revealed substantial populations of fibrolytic anaerobic fungi in fresh and air-dried feces. Populations in fresh feces were equivalent to those in ruminal contents, but declined exponentially with time in dry feces. Minimum values were obtained from dry feces 90 days after drying, and anaerobic fungi were detectable for up to 210 days thereafter.

Journal Article↗

Effect of cimetidine on intestinal absorption & digestive functions in mice.

Oral administration of cimetidine, an antiulcerogenic drug, at a dose of 100 mg per kg body weight in mice, caused significant inhibition of glucose and amino acid uptake in small intestinal segments either after 2 and 24 h (single treatment) or 15 days (daily). Cimetidine also caused a significant decrease in intestinal brush border membrane associated enzymes, sucrase, lactase, maltase and alkaline phosphatase, but increases the activity of leucine aminopeptidase. Kinetic analysis indicated that cimetidine decreased the maximum of apparent initial enzyme velocity (Vmax) of disaccharidases, while substrate affinity constant (Km) was not altered, indicating the noncompetitive nature of inhibition. However, the inhibition of alkaline phosphatase was found to be of mixed type as both Km and Vmax were altered. In vitro addition of cimetidine also produced significant inhibition of enzymes, the inhibition constant (Ki) for sucrase, lactase, maltase and alkaline phosphatase being 22.8, 4.5, 11.5 and 4.8 mM, respectively. It was further observed that in vitro addition of cimetidine also decreased Vmax in case of maltase, sucrase and lactase, Km was unchanged, whereas in case of alkaline phosphatase there was a decrease in Vmax and increase in Km, as compared to the controls.

Absorption↗

Mathematical integration of protein metabolism in growing lambs.

A mathematical integration of whole-body protein synthesis and degradation based on protein metabolism in 10 individual tissues in growing lambs is described. The tissues represented are adipose, central nervous system (CNS), gastrointestinal tract (GIT), heart, kidney, liver, muscle, pancreatic and salivary glands (PSG), reticuloendothelial system (RES) and skin, together with a blood pool of amino acids. The fluxes represented in the equations are generally assumed to follow simple or modified mass-action kinetics. The fractional rates for protein synthesis in each tissue were calculated from published values for lambs, where these were available, or alternatively derived using assumptions based on data obtained with rats. The initial protein content of each tissue and the fractional degradation rate were assigned values calculated using data from a slaughter experiment. The model was used to examine whole-body protein synthesis at different rates of growth and to compare the relative contributions of each tissue. The GIT (25-26%) and skin (23-26%) had the highest contributions to total protein synthesis, followed by muscle (21-26%), liver (13-14%), RES (6-7%) and PSG (3-6%), while adipose, CNS, heart and kidney together contributed less than 5%. These values agree reasonably well with experimental values, and thus the model can be used to examine the effect of different growth rates on protein metabolism and its associated energy costs.

Amino Acids↗

Simulation of the energy costs associated with protein turnover and Na+,K+-transport in growing lambs.

A mathematical representation of the energy-requiring processes of protein turnover and Na+,K+-transport in the tissues of growing lambs is described. This model was then used to examine the relative contributions of these processes to ATP expenditure at two different growth rates (90-230 g/d). Protein turnover accounted for 19% of whole-body ATP expenditure at both growth rates examined, with the gastrointestinal tract (GIT), accounting for 25-27%, muscle for 21-26%, skin for 23-26% and liver for 13% of total protein turnover energy costs. The contribution of Na+,K+-transport increased from 18 to 23% of whole-body heat production as growth rate increased, with the GIT accounting for 39 and 50%, muscle for 17 and 10% and liver for 18 and 23% of total Na+,K+-transport costs at low and high nutrient inputs, respectively. Thus, protein turnover accounted for 19% of the increment in ATP expenditure due to the increased nutrient input at the higher rate of growth, while Na+,K+-transport accounted for 39%, and fat turnover and accretion accounted for 25%, leaving 17% of the ATP increment unaccounted for.

Adenosine Triphosphate↗

Ostertagia ostertagi infection in the calf: effects of a trickle challenge on appetite, digestibility, rate of passage of digesta and liveweight gain.

The effects of a trickle challenge with the equivalent of 10,000 infective Ostertagia ostertagi larvae per day on appetite, digestibility, rate of passage of digesta and liveweight gain were investigated in 12 calves assigned to infected, pair-fed control and ad libitum-fed control groups. Digestibility of cellulose, nitrogen, organic matter and dry matter was determined using insoluble acid detergent fibre as a marker on two occasions during the study: (i) Between days 31 and 38, when abomasal dysfunction was greatest; and (ii) between days 52 and 58, beginning approximately one week after anthelmintic treatment (day 46). Rate of passage of digesta was measured using chromium mordanted hay, fed to each calf after each digestibility study period. Voluntary feed intake of the infected group was significantly reduced from day 37 with the greatest depression (77 per cent) occurring just before anthelmintic treatment. The drop in appetite was responsible for nearly 73 per cent of the difference in liveweight gain between the infected and ad libitum fed control groups. The apparent digestibility coefficient of nitrogen was significantly depressed (22 per cent) in the infected group though was restored to control levels by anthelmintic treatment. The rate of passage of digesta was significantly reduced in both pair-fed control (50 per cent) and infected (74 per cent) groups. Anthelmintic treatment increased the latter though only to pair-fed control group levels. It is suggested that the marked hypergastrinaemia seen in the infected calves may have been in part responsible for the decreased rate of passage of digesta and in turn for the drop in appetite.

Animals↗

Ostertagia ostertagi infection in the calf: effects of a trickle challenge on the hormonal control of digestive and metabolic function.

Metabolic effects of a trickle challenge with the equivalent of 10,000 infective Ostertagia ostertagi larvae per day were investigated in 12 calves allocated to infected, pair-fed control or ad libitum-fed control groups. Changes in hormone levels reflecting abomasal, pituitary and pancreatic function were monitored using radioimmunoassay techniques previously validated for use in cattle. A range of metabolic profile parameters and blood metabolites was also measured. Feed intake of the infected calves began to decline as blood gastrin and pepsinogen levels reached a peak. The depression in appetite recorded in this group was responsible for significant increases in plasma urea and non-esterified fatty acid levels and associated with an increase in growth hormone/insulin ratio. No significant difference in glucagon levels was recorded between groups. A decline in blood albumin values was also shown in the infected group and associated with a drop in nitrogen digestibility. A significant depression in circulating calcium levels was related to either the hypoalbuminaemia or impaired mineral absorption in the intestine. A decrease in plasma cholesterol values in the infected group was associated with changes in digestive function.

Animals↗

Effect of antiulcerogenic drug, ranitidine, on intestinal absorption and digestive functions in mice.

Oral administration of antiulcerogenic drug ranitidine significantly inhibits glucose and amino acid uptake in small intestinal segments. It also inhibits activities of brush border membrane disaccharidases and alkaline phosphatase but increases the activity of leucine aminopeptidase. Kinetic analysis reveals noncompetitive and mixed type of inhibition for disaccharidases and alkaline phosphatase, respectively. In vitro addition of the drug to membrane preparation shows similar type of results as seen in vivo with the inhibition constant (ki) for sucrase, lactase, maltase and alkaline phosphatase as 12.5, 5, 11.5 and 19.5 mM, respectively.

Animals↗

Chemotherapy for the primary treatment of osteosarcoma: population effectiveness over 20 years.

Examination of the survival rate of 5-year cohorts with primary osteosarcoma registered by the Thames Cancer Registry between 1963 and 1982 and followed up to the end of 1984 showed a borderline significant improvement in survival (test for trend p = 0.05) for patients aged under 25 years at registration, but not for patients 25-64 years. A Cox's proportional hazards model was used to identify effects of sex, period of treatment, whether the patient received chemotherapy, and experience of the hospital. For patients aged under 25 years, a significant (p = 0.02) trend of improved survival was seen among the most recent cohort, and the greater the treatment experience of the hospital, possibly the better the results (p = 0.11), although selective referral cannot be excluded as a reason for this finding. Chemotherapy was not independently associated with survival. Period of treatment, chemotherapy, and experience of hospital were not associated with improved survival for patients aged 25-64. Recent clinical trials for primary osteosarcoma have contributed to an apparent improved survival through selection of patients with good prognosis. Claims for the efficacy of new regimens should be assessed in clinical practice by population monitoring through the analysis of cancer registers.

Adolescent↗

Protein metabolism in the rumen of silage-fed steers: effect of fishmeal supplementation.

1. Ryegrass (Lolium perenne cv. Cropper) silage was given to four Friesian steers (initial live weight (LW) 172 kg) alone or with a fishmeal supplement (150 g fresh weight/kg silage dry matter (DM)) in a balanced two-period change-over design. The dietary components were the same as those used in a recent experiment by Gill et al. (1987). All diets were offered hourly at 24 g DM/kg LW. 2. Fishmeal supplementation increased dietary nitrogen intake (P less than 0.01) and significantly increased the flow of total N (P less than 0.01), non-ammonia N (NAN) (P less than 0.01) and amino acids (P less than 0.05) at the duodenum. The increased supply of NAN to the duodenum was due largely (67%) to increased flow of undergraded dietary protein. 3. Microbial protein production was estimated simultaneously with 15N, diaminopimelic acid (DAPA) and a novel technique using L-[4,5-3H]leucine. Estimates varied with the marker and source of microbial isolate but mean values indicated that microbial N flow was significantly increased by fishmeal supplementation (P less than 0.05). The use of L-[4,5-3H]leucine as a microbial marker is justified and its possible advantages over other markers are discussed. 4. The efficiency of microbial protein synthesis was significantly increased from 30.8 g N/kg organic matter apparently digested in the rumen (OMADR) to 54.3 g N/kg OMADR by fishmeal supplementation (P less than 0.01). However, this indicates that relatively high efficiencies can be achieved with unsupplemented high quality silage supplied continuously. Rumen degradable N (RDN) supply was significantly increased by fishmeal supplementation (P less than 0.05) but apparent efficiency of capture of RDN by rumen microbes was not significantly increased. 5. Attempts were made to investigate the source of N utilized by the microbes on the two diets by intrarumen infusions of (15NH4)2SO4 and L-[4,5-3H]leucine but these were confounded by rumen-mixing problems. Findings obtained suggest that a lower proportion of microbial N may have been derived from rumen ammonia when the silage was supplemented with fishmeal but no differences in the extent of direct incorporation of leucine into microbial protein were observed. This could indicate an increase in microbial peptide uptake on the fishmeal-supplemented diet. However, evidence was also obtained suggesting that the improvement in microbial protein synthetic efficiency with supplementary fishmeal was also due to the provision of a more continuous supply of nitrogenous substrates for microbial growth, as a result of hourly feeding.(ABSTRACT TRUNCATED AT 400 WORDS)

Animal Feed↗