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Biomedical subjects

H M Smith

Publications and source records attributed to H M Smith.

At least 73 records · Page 4Linked to original sources
PubMed1987

Loss of HBsAg with interferon therapy in chronic hepatitis B virus infection.

46 male chronic hepatitis B virus (HBV) carriers with active viral replication were randomised, with stratification for histology and sexual preference, to receive six months' lymphoblastoid interferon or no therapy. After nine to eighteen months' follow-up, HBeAg was no longer detectable and anti-HBe was present in 6 of the 23 treated patients. HBsAg was not detectable in 5 of these patients and 3 had anti-HBs. All of the controls remained positive for HBeAg and HBsAg. Seroconversion from HBeAg to anti-HBe was preceded in all cases by a pronounced increase in serum aspartate aminotransferase levels of more than ten times the upper limit of normal at eight to twelve weeks; this response was exclusively associated with interferon therapy. These results suggest that loss of HBsAg and a hepatitis-like illness in the third month of therapy are direct effects of interferon treatment.

Adult↗
PubMed1987

Hepatitis B vaccine: immunogenicity and follow-up including two year booster doses in high-risk health care personnel in a London teaching hospital.

One hundred forty-four adult health care personnel (aged 18-62 years, median 33 years) considered at high risk of future HBV infection were vaccinated with a plasma-derived hepatitis B vaccine (20 micrograms HBVax at 0, 1, and 6 months) and followed-up for 2 years. Anti-HBs was present in only 6.9% prior to vaccination, and prescreening to detect this group would not have been cost-effective. At 9 months, 8.3% were nonresponders and a further 9% had anti-HBs levels less than 50 mIU/ml. Multivariate analysis showed that age was the single most important determinant of a poor response. In 47 of 52 individuals retested 2 years later, anti-HBs levels had fallen by 80% or more, and in four it had become undetectable. Response to a booster dose at this stage was excellent, with anti-HBs levels 3 months later much higher than at the end of the initial course. Additional booster doses of vaccine in two of the initial nonresponders at 14 and 22 months, respectively, also led to seroconversion. Although a significant proportion of health care workers in this study did not make a satisfactory response to the hepatitis B vaccine, later booster doses were very effective in subsequently increasing anti-HBs levels.

Adolescent↗
PubMed1986

Effects of ethanol ingestion on the metabolism of a hepatotoxic dose of paracetamol in mice.

After administration to mice of a hepatotoxic dose of paracetamol (400 mg/kg body wt, p.o.) peak plasma concentrations of the drug and its glucuronide were approximately 900 microM around one hour. Corresponding levels of the sulphate, mercapturate and cysteine conjugates were approximately 100, 35 and 20 microM, respectively. Urinary excretion accounted for 55% of the administered drug 31 h after dosing. Of this total, 64.7% was paracetamol glucuronide, 17.9% paracetamol cysteine, 10.4% paracetamol sulphate, 0.5% paracetamol mercapturate and 6.5% unchanged drug. One hour after acute ethanol administration (3 g/kg, p.o., concomitantly with paracetamol) plasma levels of the glucuronide, cysteine and mercapturate conjugates were decreased by approximately 50%. There were reductions in the urinary excretion of the glucuronide (-13%) and cysteine conjugates (-24%), but increases in the amounts of mercapturate (+52%), sulphate +11%) and unchanged drug (+81%). Chronic ethanol ingestion (15 g/kg per d for 28 d) caused a transient initial increase in plasma paracetamol cysteine (+32%) and mercapturate (+41%) concentrations, but the only substantial change in urinary excretion was a 29% increase in the amount of paracetamol glucuronide. After chronic ethanol consumption, acute ethanol administration had a transient inhibitory effect on paracetamol mono-oxygenation, but glucuronidation was unaffected (as judged by plasma concentrations). Only paracetamol mercapturate excretion was substantially affected (+64%).

Acetaminophen↗
PubMed1985

Effects of ethanol administration on rat liver plasma membrane-bound enzymes.

Changes in the properties of rat liver plasma membranes were examined in studies designed to differentiate between direct and metabolic effects of acute and chronic ethanol ingestion. One hour after a single dose of ethanol (3 g/kg body weight) there were increases in Na+,K+-ATPase (32%) and 5'-nucleotidase (36%), and hepatic concentrations of ethanol and acetaldehyde were approximately 23 mM and 50 microM, respectively. Na+,K+-ATPase and 5'-nucleotidase activities in liver plasma membranes from control rats were not significantly changed by in vitro addition of 30 microM acetaldehyde or 50 mM ethanol. Increases in Na+,K+-ATPase (approximately 20%) and 5'-nucleotidase (approximately 30%) were also observed in liver plasma membranes isolated from rats 16 hr after feeding ethanol or sucrose supplements for 17 days. The intake of calories from dietary protein and lipid was decreased by about 25% in both the ethanol and sucrose-fed animals. Na+,K+-ATPase activities in liver plasma membranes isolated from control rats were inhibited (approximately 20%) by 100 mM ethanol in vitro, whereas no inhibition was observed using membrane preparations from rats fed ethanol or sucrose supplements. Our results show that changes in liver plasma membrane enzyme activities associated with a single dose of ethanol are not a direct effect correlated with blood, hepatic or plasma membrane concentrations of ethanol or acetaldehyde. Chronic ingestion of ethanol or sucrose supplements had similar effects on liver plasma membrane enzyme characteristics and parallel changes in nutrient intake may be a more feasible explanation of these results than any analogous direct effects of the two compounds.

5'-Nucleotidase↗
PubMed1985

Effects of ethanol ingestion on the hepatotoxicity and metabolism of paracetamol in mice.

The influence of ethanol on paracetamol-induced liver damage was studied in mice and related to changes in microsomal monooxygenases and plasma paracetamol metabolites in the same group of animals. Paracetamol (400 mg/kg body wt, p.o.) was administered alone or simultaneously with ethanol (3 g/kg, p.o.) to mice fed either a chow diet or pretreated for 4 weeks with a liquid diet containing ethanol (20% of energy). Acute ethanol administration protected against paracetamol hepatotoxicity, but this protection was complete only in mice not fed ethanol previously. Acute ethanol administration also appeared to reduce paracetamol monooxygenation in vivo, but ethanol (50 mM) added to microsomal incubations in vitro had no significant effect on paracetamol activation and covalent binding. The chronic ingestion of ethanol in the diet increased paracetamol-related liver damage, but there appeared to be no induction of paracetamol monooxygenation in these animals. We are unable to confirm current concepts that the potentiation of paracetamol hepatotoxicity by chronic ethanol ingestion and its reduction by acute ethanol administration result solely from contrasting effects of ethanol on cytochrome P-450, and alternative explanations are proposed.

Acetaminophen↗
PubMed1984

Use of a direct high performance liquid chromatography method for multiple testosterone hydroxylations in studies of microsomal monooxygenase activities.

A high performance liquid chromatography method is described for separation of the products of testosterone monooxygenation . The method involves direct injection onto a reverse phase octadecylsilane column of the supernatant from incubations containing as little as 25 micrograms microsomal protein. Isocratic elution with formate buffer/acetonitrile and detection at 254 nm permits the separation and simultaneous quantitation of multiple discrete testosterone-derived peaks on the chromatogram. The production of the eight major oxygenated testosterone metabolites in hamster liver microsomes was determined. This profile was altered uniquely after pretreatment with either phenobarbitone, beta-naphthoflavone, rifampicin or pregnenolone 16 alpha-carbonitrile. These changes reflected analogous dissimilar effects of the enzyme inducers on the metabolism of the exogenous cytochrome P-450 substrates aldrin, acetanilide, benzo[alpha]pyrene and ethylmorphine. Therefore, the testosterone assay provides a sensitive and effective method for separating and quantitating testosterone monooxygenation products and may offer a single alternative to the use of multiple exogenous substrates for categorizing and defining the metabolic activity of cytochromes P-450.

Acetanilides↗
PubMed1984

Effects of ethanol and enzyme-inducing agents on the monooxygenation of testosterone and xenobiotics in rat liver microsomes.

The simultaneous production of multiple testosterone oxidation products in hepatic microsomal incubations was monitored after injection of a post-trichloroacetic acid supernatant directly onto a reverse-phase high-performance liquid chromatography column. Twelve testosterone-derived metabolite peaks were detected on the chromatogram and the relative proportions of these products were changed distinctively after pretreatment of rats with phenobarbitone, beta-naphthoflavone and pregnenolone 16 alpha-carbonitrile. Chronic ingestion of ethanol (35% of total energy in a nutritionally adequate liquid diet) modified oxidative testosterone metabolism differently from the other enzyme inducers and reduced plasma testosterone levels relative to values in animals pair-fed the control liquid diet. Modifications to the metabolism of xenobiotic substrates after ethanol treatment confirmed that ethanol had changed the types and amounts of cytochrome P-450 in microsomal preparations. Differences in testosterone metabolite profiles between control and ethanol-treated male and female rats suggested that these results were not a consequence of ethanol-induced decreases in circulating levels of testosterone influencing the constitutive cytochrome P-450 isoenzymes. These experiments confirm that analysis of testosterone metabolites by high-performance liquid chromatography is a useful approach for detecting and discriminating between the metabolic capacity of cytochrome P-450 in microsomal preparations. In addition, increases in the rates of some testosterone hydroxylations after ethanol ingestion, in conjunction with known effects of alcohol on testosterone homeostasis, may contribute to the hypogonadism seen in male chronic alcoholics.

Androstenedione↗
PubMed1983

Ovarian, oviductal, and adrenal vascular connections in female lizards (genus Anolis).

The urogenital blood vessels of Anolis equestris and A. carolinensis were studied using dissection, injection of silicone rubber, and histology. A new blood-vascular connection between small veins in the pampiniform plexus at the base of the ovary and an ostial extension of the secondary oviductal vein is described. Chemical messengers could thus be carried in the blood from the ovarian venous drainage to the oviduct. Furthermore, close apposition of the secondary oviductal vein and artery provides an anatomical basis for countercurrent exchange of these messengers. A circular venous arcade, involving the supracardinal vein and branches of the oviductal veins, also is described; this arcade could serve to deliver adrenal hormones to each oviduct.

Adrenal Cortex Hormones↗
PubMed1982

Effect of isoniazid administration on selected rat and mouse hepatic microsomal mixed-function oxidases and in vitro [14C]acetylhydrazine-derived covalent binding.

The effect of isoniazid on selected microsomal mixed-function oxidase activities and on the microsomal metabolism of its own metabolite, acetylhydrazine, to a highly reactive compound which covalently binds to intracellular macromolecules was characterized in male C57BL6 mice and male Sprague-Dawley rats. In comparison with controls, isoniazid pretreatment of rats significantly increased the sp. act. of acetanilide 4-hydroxylase and the in vitro [14C]acetylhydrazine-derived covalent binding to hepatic microsomes but significantly decreased the sp. act. of benzo[a]pyrene hydroxylase and testosterone 16 alpha-hydroxylase. Isoniazid treatment of mice had no effect on any of these parameters except for a significant reduction in sp. act. of testosterone 7 alpha-hydroxylase. Thus the pathway of isoniazid metabolism leading to the formation of reactive metabolites of acetylhydrazine is enhanced by isoniazid pretreatment in rats but not in mice. The presence of similar routes of isoniazid metabolism in man may account for the 8.7-24% incidence of subclinical hepatocellular damage observed in patients receiving isoniazid alone in the chemoprophylaxis of tuberculosis.

Animals↗
PubMed1982

Parasitisms among wild swine in southeastern United States.

Examination of 187 wild swine from 20 locations in 11 southeastern states revealed at least 25 species of endoparasites and 7 species of ectoparasites. Three parasites of public health importance (Sarcoptes scabiei, Spirometra sp, and Toxoplasma gondii) were disclosed by this study. The absence of Trichinella spiralis indicates that wild swine in the Southeast are not a reservoir for Tr spiralis.

Animals↗
PubMed1981

Prevalence and distribution of Sarcocystis sp among wild swine of southeastern United States.

Digestive techniques revealed Sarcocystis sp infection in 62 of 192 (32%) wild swine collected in Alabama, Arkansas, Georgia, Louisiana, Mississippi, North Carolina, South Carolina, Tennessee, Virginia, and West Virginia. Sarcosporidia were not detected in wild swine of Florida and were rarely found in the lower coastal plains of Georgia, Mississippi, and South Carolina. Swine from mountainous terrain in North Carolina, Tennessee, and West Virginia and bottomland floodplain regions of Alabama, Arkansas, and Louisiana were most frequently infected. Infections by sarcocystis sp may have been spread via swine relocated from mountainous regions to some other locales. Upon ingestion of infected pork from wild swine of Tennessee and West Virginia, dogs, but not cats, shed sporocysts morphometrically identical to Sarcocystis suicanis.

Animal Population Groups↗