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Biomedical subjects

M J Hall

Publications and source records attributed to M J Hall.

At least 109 records · Page 6Linked to original sources

Tsetse and trypanosomiasis survey of Southern Darfur province, Sudan. II. Entomological aspects.

Atsetse survey of Southern Darfur province, Sudan showed that the distribution of the only species present, Glossina morsitans submorsitans, had not appreciably altered over 10 years. Fly populations are most dense south of the Wadi Umbelasha but light infestations are found in the woodlands north of this riverine system to a latitude of about 10 degrees 15' N. Data are given on host availability which is thought to be the major factor determining tsetse distribution. The relative importance of tsetse and of tabanids as transmitters of bovine trypanosomiasis in the province is discussed. The evidence indicates that tsetse are very much more important and that cattle are most at risk of contracting infections during their dry season southerly migrations to the tsetse belts especially during their "Rushash" migration at first rains. Possibilities of tsetse control are discussed but in the short term trypanosomiasis control is most likely best achieved by chemical prophylaxis/therapy of cattle at risk.

Animals↗

Synergistic antibacterial activity between L-norvalyl-L-1-aminoethylphosphonic acid and nocardicin A.

The phosphonopeptide L- norvalyl -L-1- aminoethylphosphonic acid [ Nva -Ala(P)] has been studied in combination with 12 beta-lactam antibiotics for activity against Pseudomonas aeruginosa. Nocardicin A was found to give the most potent synergistic combination with Nva -Ala(P). This interaction was widely observed in clinical isolates of P. aeruginosa in vitro and in a mouse septicemia model. Synergy was also observed in vitro and in vivo in several other species, including Proteus mirabilis, indole-positive Proteus spp., and Serratia marcescens. The interaction between Nva -Ala(P) and nocardicin A involved a strongly bacteriolytic mechanism. In addition, the individual components were complementary to one another in their action against organisms not showing synergy. These properties resulted in a broad spectrum of activity of the combination Nva -Ala(P) plus nocardicin A when used to treat experimental gram-negative bacterial infections.

Alanine↗

Effect of wheat bran on zinc absorption.

The effect of wheat bran on zinc absorption was studied in normal volunteers using a zinc tolerance test (ZTT) and whole-body monitor to measure the 7-day percentage retention of 65zinc (65Zn). Twenty-three subjects (age 21-26 years) were randomized into three groups. All were given 5 microCi of 65Zn orally in a 10 ml solution of zinc sulphate which contained 15 mg of elemental zinc. In addition, Group A were given 20 g wheat bran, Group B 20 g Rice Krispies (a low-fibre food) and Group C had zinc alone. The differences between the retention of 65Zn in the three groups were all statistically significant (A vs B P less than 0.005; B vs C and A vs C P less than 0.001). Similarly the differences in the areas under the ZTT curves in the three groups were all statistically significant (A vs B P less than 0.005; B vs C and A vs C P less than 0.001). We conclude that wheat bran leads to a significant reduction in zinc absorption which could eventually induce a state of zinc deficiency.

Adult↗

Tsetse and trypanosomiasis survey of Southern Darfur Province, Sudan. I. Bovine trypanosomiasis.

During a survey of Southern Darfur Province, Sudan blood samples from over 4,000 migratory cattle were analysed to determine levels of anaemia and trypanosome parasitaemia by buffy coat examination of microhaematocrit centrifuged samples. Levels of trypanosomal infections in the herds correlated well with their risk of exposure to tsetse being significantly lower at increasing distance from tsetse foci. Trypansoma vivax infections predominated in all herds, increasingly so with increasing distance from tsetse foci. Packed cell volume values could not be used to assist in trypanosome diagnosis at either individual or herd levels and the lack of correlation between anaemia and parasitaemia is suggested as evidence of a degree of trypanosomal tolerance in the Western Baggara cattle. Drug use and problems of drug resistance are discussed. Bovine trypanosomiasis is largely under control at present but requires continued surveillance (particularly of drug use) to prevent future problems as tsetse/cattle interactions increase.

Animals↗

The fractional inhibitory concentration (FIC) index as a measure of synergy.

The value of the FIC index as a predictor of synergy has been investigated using the antibacterial agents alafosfalin and cephalexin combined together with themselves in fully blind experiments. Under the conditions used, even weak interaction (FIC index 0.5-0.99) proved to be statistically highly significant. The use of such fully controlled blind studies would greatly enhance the credibility of many of the claims of synergy published in the literature. The representation of results as average isobolograms is only of value with combinations which show moderate to strong interaction.

Alanine↗

Phosphonopeptides as substrates for peptide transport systems and peptidases of Escherichia coli.

Peptide transport and peptidase susceptibility of the antibacterial agent alafosfalin and other phosphonopeptides have been characterized in Escherichia coli. Phosphonodipeptides were accumulated by a process which appeared to involve multiple permeases; saturation was not achieved even at concentrations of 128 microM. Competition studies showed that these compounds had only a low affinity for the system transporting phosphonooligopeptides and were rapidly taken up by and were inhibitory to E. coli mutants unable to transport the toxic peptide triornithine. Phosphonodipeptides containing D-residues were not appreciably transported. By contrast, phosphonooligopeptides were generally transported by a distinct saturable permease system for which they had a high affinity. This system was identical to that utilized by triornithine. Phosphonooligopeptides with simple monoalkyl substituents at the amino terminus were also transported except in the case of a t-butyl substituent. The oligopeptide permease was also able to transport certain derivatives which contained some residues having D rather than L stereochemistry. Intracellular metabolism of phosphonooligopeptides was initiated almost exclusively by hydrolysis from the N terminus by an L-specific peptidase. This initial hydrolytic activity was unaffected by the aminopeptidase inhibitor bestatin, unlike the final hydrolysis step which yields L-1-aminoethylphosphonic acid from the phosphonodipeptide intermediate.

Biological Transport↗

Doves in false garb.

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International Cooperation↗

Antibacterial activity and mechanism of action of phosphonopeptides based on aminomethylphosphonic acid.

Phosphonopeptides based on aminomethylphosphonic acid as the C-terminal residue linked to L-amino acids possessed antibacterial activity in vitro and in vivo. Analogs in this series were generally less potent than corresponding compounds based on L-1-aminoethylphosphonic acid such as alafosfalin (L-alanyl-L-1-aminoethylphosphonic acid). Significant differences in antibacterial spectra were observed. The mechanism of action involved active transport of the peptide mimetics into the bacterial cells, followed by intracellular release of high concentrations of aminomethylphosphonic acid which inhibited bacterial cell wall biosynthesis. Aminomethylphosphonic acid behaved as a mimetic of both D- and L-alanine and inhibited D-Ala-D-Ala synthetase (EC 6.3.2.4.), alanine racemase (EC 5.1.1.1.), and UDP-N-acetylmuramyl-L-alanine synthetase (EC 6.3.2.8.). The minimal inhibitory concentration of L-norvalyl-aminomethylphosphonic acid was essentially unaffected by the presence of D-alanine, whereas the activity of the corresponding L-norvalyl derivative of L-1-aminoethylphosphonic acid was markedly decreased. Substantial differences in the inhibitory and lytic activity of the L-norvalyl derivatives of aminomethylphosphonic and L-1-aminoethylphosphonic acids were also observed when these agents were combined with other inhibitors of bacterial cell wall biosynthesis.

Animals↗

Clinical experience of zinc supplementation during intravenous nutrition in Crohn's disease: value of serum and urine zinc measurements.

Serum zinc concentrations and urine zinc excretion have been studied in 10 patients with severe Crohn's disease before and during 59 patient-weeks of intravenous nutrition. Before serum zinc concentrations (9.9 +/- 1.0 mumol/l: mean +/- SEM) and urine zinc excretion (3-3 +/- 0.6 mumol/24h) were less than controls (p less than 0.01). No patients had clinical signs of zinc deficiency before intravenous nutrition and none developed signs during it. There was no overall change in serum zinc concentrations, despite improvements in body weight, skinfold thickness, and mid-arm circumference in all patients, and increased serum albumin and serum transferrin concentrations during all but two periods of intravenous nutrition. Nor was there any relationship between serum zinc concentrations and zinc uptake (up to 220 mumol/day), serum zinc concentrations remaining significantly lower than control levels. Urine zinc excretion during the first week of intravenous nutrition showed a 1.2 to 53-fold increase (mean 11-fold) over pre-intravenous nutrition levels, and a positive relationship was demonstrated between zinc intake and urine zinc excretion. It is suggested that zinc supplied by the intravenous route is inefficiently transported to the tissues, and that some is excreted in the form of small molecular weight chelates into urine. Recommendations are made for the supply of intravenous zinc, based on monitoring urine zinc excretion in individual patients.

Adolescent↗

Gemfibrozil--the effect of biliary cholesterol saturation of a new lipid-lowering agent and its comparison with clofibrate.

Clofibrate is known to increase cholesterol saturation of bile and the prevalence of gallstones. We studied 10 healthy volunteer subjects to determine the effect of gemfibrozil (a new lipid-lowering agent) on biliary cholesterol saturation and to compare it with that of clofibrate. Biliary cholesterol saturation indices were calculated on fasting duodenal bile samples collected before and after administration of each drug for 4 weeks using a 4-week "washout" period between each preparation. There was a statistically significant rise in the cholesterol saturation index from a control value, taken as the mean of 2 samples, of 1.226 (0.785--1.526), median (range), to 1.547 (0.807--1.781) after clofibrate, P less than 0.05, but the rise to 1.352 (0.840--2.686) after gemfibrozil was not significant. However, direct comparison of the cholesterol saturation indices on clofibrate and gemfibrozil revealed no statistically significant difference. Only prospective clinical trials will establish definitively the risk of cholelithiasis on gemfibrozil but these results suggest that this drug is unlikely to have an advantage over clofibrate in this respect.

Bile↗

Isolation of haemagglutinating adeno-like virus related to virus 127 from an Australian poultry flock with an egg drop syndrome.

An egg drop syndrome within Australian broiler poultry is described. The syndrome was characterised by delayed onset of laying, a lower peak in egg production and a drop in egg production shortly after reaching peak production. Antibody to virus 127 was detected in 102 of 106 fowl serums tested. Two haemagglutinating viruses were isolated from one affected flock and one was subjected to further study. It was adenovirus-like on electron-microscopic examination and haemagglutination was not inhibited by a specific antiserum to Newcastle disease virus. An antiserum was raised in White Leghorn fowl against the isolate and this antiserum was found to cross-react with virus 127, a prototype virus of Egg Drop Syndrome 76.

Adenoviridae↗

Antibacterial properties of alafosfalin combined with cephalexin.

The phosphonopeptide alafosfalin (L-alanyl-L-1-aminoethylphosphonic acid) exhibited synergy in vitro and in animal studies against a range of bacterial genera when combined with cephalexin. Alafosfalin also showed synergy with mecillinam and, to a much lesser extent, with ampicillin. Synergy with cephalexin was more pronounced when the bacteria were relatively insensitive to the beta-lactam component. The action of this combination involved both an inhibitory and a bacteriolytic mechanism which was abolished by concurrent treatment with the aminopeptidase inhibitor, bestatin. Regrowth of subpopulation resistant to either component was markedly reduced by the combination. The potential of alafosfalin combined with cephalexin for use in therapy is discussed.

Alanine↗