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Biomedical subjects

S Oie

Publications and source records attributed to S Oie.

At least 19 recordsLinked to original sources
PubMed1992

Microbial contamination of brushes used for preoperative shaving.

Microbial contamination of brushes used for preoperative shaving was investigated. Of the 24 brushed examined, 18 were contaminated with 10(6)-10(9) colony forming units (cfu) per brush. Non-fermentative Gram-negative bacilli such as Pseudomonas aeruginosa and Xanthomonas maltophilia, and yeast-like fungi such as Candida parapsilosis were the primary contaminants. The mean bacterial count on the skin after the use of contaminated brushes (having a mean bacterial count 2.2 x 10(8) cfu) in 14 subjects was 4.6 x 10(5) cfu 25 cm-2, which was about 100 times (p less than 0.001) the control level. Contaminated brushes could not be disinfected with 80% ethyl alcohol, 0.1% sodium hypochlorite or 0.5% chlorhexidine. These findings suggest that the use of brushes should be avoided for preoperative shaving with a razor, and that sterile gauze and shaving foam should be used instead of a brush and soap.

Candida↗
PubMed1992

Microbial contamination of enteral feeding solution and its prevention.

In an investigation of microbial contamination of enteral feeding solutions, all 22 residual solutions obtained immediately after administration were contaminated at concentrations of 10(3) to 10(6) viable counts/ml. Major contaminants were glucose-nonfermenting gram-negative bacilli such as Pseudomonas aeruginosa and Acinetobacter calcoaceticus var anitratus. Contamination seemed to have been caused by frequent reuse of bag-type containers and the infusion tubes connected to the bags, neither of which can be washed or dried. Decontamination methods were evaluated by using polypropylene containers that can be washed and disinfected for administration. Few Serratia marcescens on the inside wall of the container were removed by rinsing with tap water, alone or in combination with detergent scrub. Tap water and detergent plus air-drying at 56 degrees C for 1 hour reduced Serratia marcescens only somewhat. Tap water and detergent plus immersion in 0.01% sodium hypochlorite for 1 hour or in water at 70 degrees C for 3 minutes eliminated all 10(11) cells of Serratia marcescens.

Colony Count, Microbial↗
PubMed1992

Pharmacokinetics of moclobemide in male, virgin female, pregnant and nursing rats.

The disposition of moclobemide, a reversible inhibitor of monoamine oxidase isoenzyme A was studied in male, virgin female, pregnant and nursing rats. The average clearance in control rats (male and female) was 36 mL min-1 kg-1, the initial volume of distribution 1.4 L kg-1, the volume of distribution at steady state 2.3 L kg-1 and the terminal half-life 59 min. The blood-to-plasma concentration ratio of moclobemide was 0.84 giving rise to an average blood clearance of 30 mL min-1 kg-1. The clearance values in rats were higher than in man but as a fraction of hepatic blood flow were similar (36 vs 45%). The volume of distribution at steady state was approximately twice as high as in man while the half-life was similar. Pregnant and nursing rats showed no statistically significant differences in their disposition parameters for moclobemide compared with virgin female rats. Nursing rats had statistically significantly lower concentrations of the moclobemide N-oxide metabolite than did pregnant and control rats. Generally lower concentrations of the lactam metabolite were also found in this group although the differences did not reach statistical significance. Moclobemide as well as the N-oxide and lactam metabolites were found in the amniotic fluid suggesting that moclobemide is capable of crossing the placental barrier.

Animals↗
PubMed1992

Elimination of non-reactive and weakly reactive human alpha 1-acid glycoprotein after induction of the acute phase response in rats.

The disposition of concanavalin A (Con A)-non-reactive and Con A-reactive human alpha 1-acid glycoprotein (AAG) was studied in normal male rats and in acute phase response-activated male rats. Activation of the acute phase response was made using a subcutaneous administration of ethynyloestradiol in sesame oil. This technique increased the endogenous AAG concentration 7-fold. In control rats the two forms of human AAG showed identical kinetics with an average clearance of 5.4 mL h-1 kg-1, terminal half-life of 13.5 h and a volume of distribution (steady state) of 91 mL kg-1. In the acute phase response-activated animals, both the clearance and volume of distribution were larger: the average clearance of the Con A-non-reactive AAG was 10.2 mL h-1 kg-1, the volume of distribution (steady state) 152 mL kg-1 and the terminal half-life 11.7 h. The Con A-reactive AAG had a clearance of 14.7 mL h-1 kg-1, a volume of distribution (steady state) of 262 mL kg-1 and a half-life of 15.8 h. The results indicate that not only does activation of the acute phase response alter the kinetics of AAG but that the change is different for the different types of AAG.

Acute-Phase Reaction↗
PubMed1992

Microbial contamination of ambient air by ultrasonic humidifier and preventive measures.

The microbially contaminated ultrasonic humidifier (UH) causes humidifier fever. The number of airborne viable bacteria was determined when the UH was operating, and other methods to humidify the air of hospital wards were also examined. A UH contaminated with 10(5) bacteria ml(-1), a level common in hospitals, increased the bacterial count in the air from 860 m(-3) to 88,000 m(-3) at a distance of 3 m from the humidifier. Thus UH in hospitals may contaminate the air and be a potential hazard to patients. Contamination was slight when a washable and disinfectable ultrasonic nebulizer was used with disinfection at 24 h intervals. In tracheostomy patients requiring a high degree of air humidification, ultrasonic nebulizers which are readily washed and disinfected are recommended.

Aerosols↗
PubMed1991

The effect of alpha 1-acid glycoprotein on the pharmacological activity of alpha 1-adrenergic antagonists in rabbit aortic strips.

The pharmacological activity of three alpha 1-adrenergic antagonists, prazosin, tiodazosin and WB4101 has been studied in the presence and absence of 20 microM alpha 1-acid glycoprotein (AAG) in rabbit aortic strips, and measured as the ability to increase the EC50 value of the alpha 1-adrenergic agonist phenylephrine. For all three drugs, the presence of AAG diminished the pharmacological activity when compared with equivalent unbound concentrations in the absence of AAG. In the presence of AAG the EC50 value of phenylephrine at 5.69 nM unbound prazosin was on average 47% lower than in the absence of AAG (P less than 0.002), at 122 nM unbound tiodazosin, 39% lower (P less than 0.01), and at 25.6 nM unbound WB4101, 68% lower (P less than 0.002). Albumin showed no ability to modify the alpha 1-adrenergic blocking activity of prazosin (P greater than 0.7). The EC50 value for phenylephrine in the absence of antagonists was not affected by AAG. The effect of AAG on the antagonistic activity of prazosin was concentration-dependent with a maximum suppression of prazosin activity of 79% and with a half-maximum concentration of 1.1 microM AAG. AAG significantly decreased prazosin's ability to reduce alpha 1-adrenergic stimulation of calcium influx (P less than 0.05), while it had no effect on prazosin's ability to decrease alpha 1-adrenergic-stimulated formation of inositol phosphate. These results suggest that the effect of AAG on adrenoceptors appears to act selectively via alpha 1 a-receptors. Consistent with these observation was the observation that WB4101, a selective alpha 1a-antagonist was more affected by AAG than was prazosin or tiodazosin.

Adrenergic alpha-Antagonists↗
PubMed1991

[Combination chemotherapy with orally administered UFT and leucovorin (LV)].

We evaluated the efficacy of the combination therapy of UFT with Leucovorin (LV) against mouse colon adenocarcinomas and human colon adenocarcinoma. In vitro studies, it was shown that LV potentiated the cytotoxicity of FUra against 7 out of 9 cell lines used in this experiment. In vivo studies, the antitumor activity of UFT against mice bearing colon 38 adenocarcinoma was increased following administration of LV either before, after or at the time of treatment with UFT. Further studies were performed on the combination effect of UFT and LV against mouse colon 26 adenocarcinoma and human colon adenocarcinoma KM20C. Consequently, the combined treatment of UFT with LV was more effective than UFT alone against two cell lines. Our studies suggest that combination chemotherapy of UFT with LV is a promising approach for the treatment of a human colon cancer in clinical practice.

Adenocarcinoma↗
PubMed1990

Mechanism of action of a new macromolecular antitumor antibiotic, C-1027.

C-1027 is a new antitumor protein antibiotic containing a non-protein chromophore. The active moiety and the mechanism of action of this antibiotic were studied. C-1027 and its chromophore inhibited the growth of KB carcinoma and L1210 leukemia cells, even at extremely low concentrations. C-1027 inhibited DNA synthesis of L1210 cells and cleaved cellular DNA in a drug concentration-dependent manner. C-1027 and chromophore caused directly DNA single strand breaks in the purified DNA without any supplement of reducing agents. These results suggest that C-1027 chromophore may inhibit cell growth by causing DNA breakage with subsequent inhibition of DNA synthesis.

Aminoglycosides↗
PubMed1990

[Analysis of the mechanism of increased antitumor activity of UFT after combined treatment with CDDP].

Previously we have reported the efficacy of the combination therapy of UFT with CDDP against several human cancer xenografts implanted in nude mice. Among all cell lines tested, KM20C (Human colon adenocarcinoma) has shown the most pronounced synergistic antitumor effect after administration of CDDP prior to UFT. The effect of CDDP administered after UFT and that of either drug alone were weaker. To clarify the mechanism of this synergistic effect, the change of the poolsize of reduced folate in KM20C, induced by CDDP treatment, was measured. The pretreatment with CDDP increased the poolsize of CH2-H4 folate and H4 folate and increased the binding of FdUMP to the dTMP synthase of an intact cells. Based on the above data, it was concluded that the enhancement of cell sensitivity to UFT was caused by the CDDP-induced increase of the reduced folate pool, in consequence leading a better binding of FdUMP generated from UFT to dTMP synthase, a target enzyme for the antitumor activity of fluorinated pyrimidines.

Adenocarcinoma↗
PubMed1990

[Experimental study of the effect of combined treatment of UFT with CDDP on human solid tumor-xenografts in nude mice].

The effect of combined treatment of UFT with CDDP, especially the optimal time-dependent administration sequence, was studied in nude mice bearing nine human cancer xenografts derived from stomach, colon, lung, breast and uterocervical cancers following treatment with clinically equivalent doses and routes of administration. This combination treatment produced a higher response rate than a single treatment in 7 out of 9 cancers (78%). However, the combination timing of UFT and CDDP was assumed to be an important factor to produce a good therapeutic effect, since the combination effect was different by changing the treatment procedure, e.g., UFT followed by CDDP or CDDP followed by UFT. There was a low correlation between combination effect and the treatment procedure, origin of tissues, histology and doubling time of cancer cells or efficacy of a single agent. The strongest antitumor effect was observed by the treatment with UFT administered both prior to CDDP and after CDDP. Such treatment procedure seemed to be reasonable for cancers of unknown origin or character.

Animals↗
PubMed1990

Pharmacologic activity of prazosin is decreased by alpha-1-acid glycoprotein in vivo.

The pharmacologic response to drugs is generally assumed to be related to the unbound concentration of the active species. This study, however, reports that the alpha-1 adrenergic blocking activity of prazosin is lower in the presence than in the absence of the plasma protein alpha-1-acid glycoprotein (AAG), at the same unbound concentrations. This phenomenon suggests that plasma proteins can modify the activity of drugs by mechanisms other than those reflected by changes in the unbound fraction values. The pharmacodynamic activity (percentage of decrease in systolic blood pressure) of prazosin was studied in control rats and in rats that were administered 40 mg/kg of human AAG. The effect vs. log unbound concentration relationships were right-shifted in the presence of AAG both after intravenous bolus doses (160 micrograms/kg) and during intravenous infusion (0.6-2.4 micrograms/min/kg), i.e., AAG decreased the activity of unbound prazosin. The Emax and EC50 (mean +/- S.E.) values for unbound prazosin in control animals in the intravenous bolus study were 33.4 +/- 2.6% of the control blood pressure (zero time) and 6.2 +/- 1.4 ng/ml, respectively; and in AAG-treated animals 37.8 +/- 6.0% of the control blood pressure and 18.9 +/- 6.1 ng/ml, respectively. The EC50 value was statistically significantly increased in the presence of AAG (t = 4.97, P less than .001) whereas no difference was seen in the Emax value (t = 1.65, P greater than .1). The possible underlying mechanism(s) of the effect of AAG is discussed.

Animals↗
PubMed1988

Effect of altered albumin concentrations on elimination of unbound prazosin in vivo in the rat and in the isolated perfused rat liver.

Albumin is known to affect the intrinsic clearance of many compounds in the isolated perfused rat liver, but little is known of its effect in vivo. The influence of decreased albumin concentrations on clearance of unbound prazosin and intrinsic clearance of prazosin was therefore studied in vivo in rats that had undergone plasmapheresis. An approximate 30% reduction in the plasma albumin concentration was achieved in animals not given plasma expanders and an approximate 50% reduction was achieved in animals given Ficol 70 as a plasma expander. No differences were seen in the intrinsic clearances or in the clearances of unbound prazosin between control animals and plasmapheretic animals. The reason for this lack of effect is apparent from parallel studies in isolated perfused rat livers. An increase in the clearance of unbound prazosin of 27% was seen when the albumin concentration was increased from 0 to 30 microM, and of 49% when the concentration of albumin was increased to 90 microM, with no further increase at higher albumin concentration. These results, therefore, suggest that changes in the albumin plasma concentrations normally encountered clinically may have little effect on the intrinsic elimination of drugs.

Albumins↗
PubMed1988

Does alpha 1-acid glycoprotein reduce the unbound metabolic clearance of disopyramide in patients with renal impairment?

The pharmacokinetics of disopyramide was studied in 15 patients with renal dysfunction (4 with pyelonephritis, 7 with glomerular nephritis and 4 with interstitial nephritis). The elimination rate constant of unbound disopyramide was 0.094 h-1 and CLu/f (unbound clearance divided by bioavailability) was 245 ml/min. Both the unbound renal clearance (CLR) and CLu/f were highly correlated with the creatinine clearance (CLCR). The apparent unbound metabolic clearance in the patients was approximately two-fold lower than that previously reported in normal subjects. The estimated unbound metabolic clearance in the renal dysfunction patients showed a significant negative correlation with the alpha 1-acid glycoprotein (AAG) concentration and only a weak, non-significant correlation with CLCR. As AAG in the renal dysfunction subjects was increased in comparison with normal values, it is possible that AAG is a factor in the decrease in the apparent unbound metabolic clearance.

Adult↗
PubMed1988

Dose-dependent metabolism and hepatic distribution of phenprocoumon in rats.

The dose-dependency of phenprocoumon disposition was determined in rats by iv administration of 0.1 and 1.0 mg/kg doses to separate groups of animals. The intrinsic clearance (unbound clearance) was 33% lower in the animals given 1.0 mg/kg dose than in the animals given 0.1 mg/kg dose. The apparent unbound volume of distribution was 55% lower and the elimination rate constant 54% higher in the high dose group than in the lower dose group. Binding of phenprocoumon to liver showed saturability with a two- to threefold higher apparent unbound fraction of phenprocoumon in liver in animals given the high dose in comparison to animals given the low dose.

4-Hydroxycoumarins↗
PubMed1988

Sex-related differences in disposition and response to phenprocoumon in rats.

The pharmacokinetics and the pharmacological response to phenprocoumon have been studied in female and male inbred Lewis-Wistar rats. A significantly lower clearance was found in female than in male rats (7.9 +/- 1.4 vs 24.5 +/- 2.5 mL h-1 kg-1, respectively; t = 15.09, P less than 0.001) as well as a lower apparent volume of distribution (288 +/- 46 vs 617 +/- 105 mL kg-1; t = 7.58, P less than 0.001) and a longer half-life (25.5 +/- 3.4 vs 17.5 +/- 1.8 h; t = 5.16, P less than 0.001). The binding of phenprocoumon was higher in female than in male rats (fu: 0.0096 +/ 0.0008 vs 0.0124 +/- 0.0007, respectively; t = 6.66, P less than 0.001). The total (C) as well as the unbound concentration (Cu) needed to elicit a 50% decrease in the prothrombin complex synthesis rate was substantially higher in female rats: C50 was 377 +/- 98 ng mL-1 in female and 155 +/- 29 ng mL-1 in male rats (t = 5.32, P less than 0.001), whereas Cu50 was 3.6 +/- 0.7 ng mL-1 in female and 1.9 +/- 0.3 ng mL-1 in male rats (t = 5.50, P less than 0.001). However, because of the lower clearance and volume of distribution and the longer half-life in female rats, the female rats experienced a higher cumulative effect than male rats to 0.34 mg kg-1 i.v. doses.

4-Hydroxycoumarins↗
PubMed1987

Factors responsible for interindividual differences in the dose requirement of phenprocoumon.

The total and unbound plasma concentrations of phenprocoumon and the prothrombin complex activity were determined in 51 patients on phenprocoumon. A 7-fold difference in the dosing rate (10-70 micrograms/kg/day) was required to maintain the prothrombin complex activity at 11-30% of normal. The variation in dosing requirement was mainly due to interindividual differences in the intrinsic clearance of phenprocoumon and only to a minor degree to differences in sensitivity to it. On average patients with myocardial infarction required only 2/3 of the daily dose of phenprocoumon of post cardiac surgery patients and patients with thrombosis and emboli. That difference appeared to be due to higher clearance in surgical patients and to greater resistance to phenprocoumon in patients with thrombosis and emboli. The total clearance in patients varied approximately 5-fold. It was better predicted by the interindividual intrinsic clearance (r = 0.84) than by the unbound fraction (r = 0.15).

4-Hydroxycoumarins↗
PubMed1987

Bioavailability of disopyramide in normal volunteers using unbound concentration.

The pharmacokinetics of disopyramide were determined in 10 healthy volunteers after a 300 mg oral dose and again after a 2 mg/kg i.v. dose. The unbound clearance was 599 ml/min and the unbound renal clearance 310 ml/min. The terminal elimination rate constant of unbound drug was 0.180 h-1 after the i.v. dose and 0.203 h-1 after the oral dose. The absorption rate constant was 0.53(-1) and the maximum peak concentration occurred after 3.2 h. The bioavailability was 0.809 using the area under the unbound plasma concentration time curve. Although a saturable plasma protein binding was found in all subjects the bioavailability using the total concentration, in contrast to theoretical expectations, showed the same value (0.813) as the unbound concentrations.

Adult↗