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Biomedical subjects

R Drew

Publications and source records attributed to R Drew.

At least 19 recordsLinked to original sources
PubMed1992

The effects of ibuprofen enantiomers on hepatocyte intermediary metabolism and mitochondrial respiration.

In vivo and in vitro (-)R-ibuprofen is inverted to the (+)S antipode via stereoselective formation of an R-ibuprofenyl-CoA intermediate. In this study the effects of (-)R- and (+)S-ibuprofen on metabolism and respiration were studied using isolated rat hepatocytes and mitochondria. R-Ibuprofen significantly increased the lactate to pyruvate ratio, perturbed mitochondrial ketogenesis as evidenced by alterations in the beta-hydroxybutyrate to acetoacetate ratio and uncoupled mitochondrial oxidative phosphorylation. In addition, substantial dose- and time-dependent sequestration of reduced CoA (CoASH) occurred in the presence of the R enantiomer. Similarly, S-ibuprofen altered both the cytosolic and mitochondrial redox states although the magnitude of the effect was substantially less than that observed with the R enantiomer. In contrast to R-ibuprofen, S-ibuprofen did not uncouple oxidative phosphorylation or sequester hepatocyte CoASH. It is proposed that the perturbations observed in hepatocyte intermediary metabolism and mitochondrial function are attributable to a combination of the direct effects of R-ibuprofen per se and the sequestration of CoASH as R-ibuprofenyl-CoA during the process of chiral inversion. On the basis of these results, R-ibuprofen should be considered more in terms of metabolism to a reactive acyl-CoA intermediate rather than as a pro-drug for the pharmacologically active S-enantiomer.

3-Hydroxybutyric Acid↗
PubMed1979

Choleretic and cholestatic effects of infused bile salts in the rat.

In rats, at low infusion rates taurocholate (TC), taurochenodeoxycholate (TCDC) and taurodeoxycholate (TCD) each produced an increase in bile flow of 20-50%. However, at high infusion rates (5-20 mumoles min-1kg-1) the cholestatic effects of the bile salts were revealed and the relative toxicity of the bile salts was seen to be TDC greater than TCDC greater than TC.

Animals↗
PubMed1979

Effect of chlorpromazine and erythromycin on bile salt-induced cholestasis in the rat.

The effects of subacute administration of chlorpromazine HCI (CPZ), erythromycine base and erythromycin estolate on the cholestatic response to intravenous taurolithocholate (TLC) and taurochenodeoxycholate (TCDC) in the rat were investigated. All three enhanced the recovery of bile flow after TCDC but not after TLC. Erythromycin base and estolate enhanced bile flow recovery after TCDC and potentiated the increase of plasma 5'-nucleotidase, as did CPZ. Neither erythromycin estolate nor CPZ precipitated a cholestatic response in rat maintained for 9-13 days on a diet supplemented with 0.05% lithocholic acid. It is concluded that the interaction of CPZ and erythromycins with bile salts is not based on the cholestatic properties of the drugs, and hence is not a practical way of distinguishing cholestatic from non-cholestatic drugs.

Alanine Transaminase↗
PubMed1977

Phagocyte dysfunction in common variable immune deficiency.

The history of a 13-year old boy is reported who suffered from frequent bacterial, enteroviral, and protozoal infections since late infancy. A decrease in the serum levels of IgG2, IgG3, IgA, a neutrophil dysfunction, and a partial cellular immune deficiency could be demonstrated. A deficiency of folic acid produced a pancytopenia which enhanced the patient's susceptibility to infections. The combined substitution of gammaglobulins and folic acid only was able to break this vicious cycle.

Adolescent↗
PubMed1977

The dominance of vertebral column fractures associated with neurologic deficits among survivors of light-plane accidents.

The vertebral injuries sustained by 13 survivors of four light-plane crashes were reviewed. Eight patients sustained major nonvertebral injuries. Eleven patients sustained 18 lower thoracic and/or upper lumbar fractures. Eighty-five per cent of the fractures involved T12, L1, L2, or L3. Seven patients sustained vertebral burst fractures; ten sustained vertebral flexion fractures. In nine patients these vertebral fractures had associated fracture-dislocations of the posterior pedicles. Eight of these nine patients (89%) developed neurologic deficits of the conus medullaris and/or cauda equina. The severity and time of onset of these neurologic deficits were similar for the occupants of each aircraft. Downward vertical deceleration and rotational violence were the dominant forces which inflicted the vertebral column fractures which resulted in neurologic deficits.

Accidents, Aviation↗
PubMed1977

Hexobarbital pharmacokinetics in rats after ligation of the common bile duct.

Rats, with and without bile duct ligation (BDL), were injected with hexobarbital (i.p. and i.v.) and blood concentrations measured as a function of time. Analysis of these curves using a single-compartment model showed that BDL altered hexobarbital pharmacokinetics in a manner dependent upon the duration of BDL and the route of administration of hexobarbital. Clearance from the blood and the rate constant for elimination (K) were reduced after 72-hour BDL but not after 12-hour BDL. The absorption of hexobarbital after intraperitoneal injection was slowed by 12- and 72- hour BDL. Seventy-two-hour BDL also increased the volume of distribution of hexobarbital but only when the drug was administered intraperitoneally. These data are consistent with previously reported data showing impairment of hepatic microsomal drug metabolism after 72-hour BDL, but not after 12-hour BDL. We also confirmed earlier speculations that BDL decreased the absorption of intraperitoneally-administered hexobarbital, although this does not appear to be a significant factor in prolonging hexobarbital sleeping time.

Animals↗
PubMed1977

The expediency of peritoneal lavage for blunt trauma in children.

Two hundred and thirty children, ten years of age or younger, suspected of having blunt abdominal injuries underwent diagnostic peritoneal lavage. Peritoneal lavage was 99.1 per cent accurate in determining the presence or absence of abdominal injuries. One patient had a false-positive peritoneal lavage. Sixty-nine of the 70 patients with blunt abdominal injuries, who underwent peritoneal lavage, had a positive peritoneal lavage; one patient had a false-negative peritoneal levage. Ninety-one per cent of the positive peritoneal lavages were grossly positive for hemoperitoneum. All 11 children with extraperitoneal abdominal injuries had positive peritoneal lavages from associated intraperitoneal injeries. The mortality for children with blunt abdominal injuries was 19.4 per cent. Intra-abdominal injuries were solely responsible for 29 per cent of the deaths and were a major contributing factor in an additional 21 per cent of the deaths. The routine use of diagnostic peritoneal lavage during the initial evaluation of blunt abdominal trauma was, in large part, responsible for the rapid, definitive treatment which -he children with abdominal injuries received. Sixty-five per cent of the children underwent exploratory laparotomy within one hour of admission to the hospital.

Abdominal Injuries↗