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Biomedical subjects

H Mattie

Publications and source records attributed to H Mattie.

At least 127 records · Page 7Linked to original sources
PubMed1978

Cefazolin and cephradine: relationship between serum concentrations and tissue contents in mice.

The relationship between serum concentrations and tissue levels of various doses of cefazolin and cephradine was determined in experimentally infected mice. An infection was induced by injection of 5 X 10(6) Escherichia coli into the right hind leg, antibiotics were administered 1 h later. At 15-minute intervals mice were killed by exsanguination after a blood sample was taken, and the infected thigh was taken out and homogenized. The total amount of antibiotic per gram thigh muscle tissue was calculated on the basis of the concentration in the supernatant of the homogenate. From the parallel course between blood concentrations and total tissue contents it may be concluded that the thigh was easily accessible for both cephalosporins. The ratio between the total tissue content and the free serum concentrations was the same for both antibiotics despite the difference in protein binding between cefazolin and cephradine in mouse serum. This implies that the discrepancy between the relative antibacterial activity of the cephalosporins in vitro and in vivo found in earlier experiments cannot be explained by differences in accessibility of the tissue.

Animals↗
PubMed1978

The effects of a depressant and a stimulant drug on the contingent negative variation.

Three groups, each comprising eight subjects, were twice tested with an interval of one week: one group receiving 10 and 20 mg chlordiazepoxide, another group receiving 150 and 300 mg caffeine and a control group receiving placebo and 'no-drug' treatment. During each session the CNV was determined five times: one pre-drug and four post-drug measurements, each divided in a condition with and one without 'white noise'. Based on Eysenck's theory it was predicted that the CNV would increase after administering chlordiazepoxide and would decrease after administering caffeine. Furthermore it was expected that 'white noise' would attenuate the CNV of introverts and would enhance the CNV of extraverts. The first hypothesis was significantly verified comparing the chlordiazepoxide group with the caffeine group. However, making comparisons within groups, only the decrease between the measurement before taking caffeine and the first one after administering was significant. The second hypothesis could be supported for introverts only.

Acoustic Stimulation↗
PubMed1978

Probenecid and the antibacterial activity of cephradine in vivo.

The influence of probenecid on the concentrations in blood and antibacterial efficacy of cephradine was studied in experimentally infected mice. An infection was induced by injection of 5 X 10(6) Escherichia coli into the thighs of irradiated, granulocytopenic mice. Probenecid was given 1 hr later, just before the administration of cephradine. The control animals received only the vehicle. Concentrations of cephradine in blood were determined for 2 hr; the antibacterial activity was estimated from bacterial counts made in the homogenized individual thighs. The blood concentrations of cephradine were 1.77 times higher in the probenecid-treated animals than in the controls. The potency ratio for doses was 2.41, the potency ratio for the areas under the drug concentration in blood vs. time curves was 1.34, and that for the peak blood concentrations was 1.43.

Animals↗
PubMed1976

The influence of the thyroid function on the metabolic rate of prothrombin, factor VII, and factor X in the rat.

The influence of the thyroid function on the metabolic rate of prothrombin, factor VII, and X was studied in the rat. Disappearance rates of the three coagulation factors were measured after synthesis had been blocked with appropriate doses of warfarin, and reappearance rates were assessed upon induction of synthesis by high doses of vitamin K1 injected into rats displaying coumarin induced hypocoagulability. No statistically significant difference in the disappearance and production rates of any of the factors could be found between normal euthyroid rats and thyroxin-treated hypothyroid rats proven to be euthyroid. The differences between the two euthyroid groups and the hypothyroid group were highly significant, however: hypothyroidism results in an approximately 50% decrease of the metabolic rates of the three coagulation factors under study. The reappearance of the three factors, under euthyroid as well as hypothyroid conditions, showed a biphasic pattern: in the first two hours after vitamin K1 administration to warfarin treated rats, a rapid reappearance was observed, to the same extent for all three factors, in hypo- as well as euthyroid rats. This finding suggests that in vitamin K1 deficiency an intracellular accumulation of precursor proteins (PIVKAs) occurs, which after rapid conversion into biologically active coagulation factors by vitamin K1 are shed into circulation. The subsequent phase of reappearance is much slower and reflects the synthesis rate of coagulation enzymes. It is characteristic for each factor and clearly slower in hypothyroid rats than in euthyroid rats. From this an influence of thyroid function on the synthesis rate of the protein moiety of coagulation factors can be inferred. An apparent difference between disappearance and reappearance rate of the coagulation factors in the plasma, particularly pronounced for factors VII and X in euthyroid rats, could theoretically be explained as the consequence of the model used for derivation of these rates.

Animals↗
PubMed1976

Dicloxacillin and cloxacillin: pharmacokinetics in healthy and hemodialysis subjects.

Differences in the elimination, distribution, and absorption of dicloxacillin and cloxacillin were studied in a group of healthy individuals with the use of a 2-compartment model. In patients on chronic intermittent hemodialysis, only dicloxacillin was investigated and the results were compared with data obtained in earlier studies on cloxacillin and flucloxacillin. In healthy volunteers the bioavailability after oral administration of 2 gm dicloxacillin or 2 gm cloxacillin amounted to 48.8% and 36.9% of the dose, respectively, when calculated from the area under the serum concentration-time curve, and to 74.1% and 48.5%, respectively, when calculated from the urinary excretion. Individual variation in bioavailability after oral administration was slightly lower for docloxacillin than for cloxacillin. The higher serum concentrations of dicloxacillin, as compared with cloxacillin, are also attributable to slower (renal) elimination (T 1/2: 42 and 33 min, respectively). Analysis of serum concentrations after intravenous administration of 1 and 2 gm dicloxacillin to healthy subjects revealed concentration-dependent kinetics with respect ot renal elimination. In hemodialysis patients the elimination rate of dicloxacillin (T 1/2: 129 min) corresponds with the extrarenal elimination rate in healthy subjects. The bioavailability after oral administration of 1 gm in patients is good (75.9% of the dose).

Administration, Oral↗
PubMed1976

Active metabolites of isoxazolylpencillins in humans.

Metabolites of the isoxazolylpenicillins that still possessed antibacterial activity were shown to be present in urine and serum. In healthy subjects, the amounts excreted in urine were low; 10 to 23% of the excreted penicillin activities represented the metabolites. The highest amount of metabolite in urine was found for oxacillin, and the lowest was found for flucloxacillin. No extreme differences in the amounts of metabolite excreted were observed when the compounds were administered orally or intravenously. In one healthy subject metabolite levels were estimated for cloxacillin in serum. Very low levels were found, i.e., about 9% of the activity. In subjects with highly impaired renal function, the metabolite may represent up to 50% of the total level of penicillin in serum. The antibacterial activities of the different metabolites were of the same order of magnitude as those of the respective parent compounds. Also, the activity against benzylpenicillin-resistant staphylococci was retained. It is not likely that the formation of the active metabolites should influence therapeutic results.

Administration, Oral↗
PubMed1975

Pharmacokinetics of flucloxacillin and cloxacillin in healthy subjects and patients on chronic intermittent haemodialysis.

1 A pharmacokinetic study on flucloxacillin and cloxacillin was performed to investigate the factors contributing to the higher serum concentrations reported for the former after oral administration. 2 The results obtained in a study performed in a group of volunteers with flucloxacillin administered orally and by continuous infusion, were compared with the results of a similar investigation with cloxacillin. Patients on chronic intermittent haemodialysis received flucloxacillin orally and as a single i.v. injection. The results of this part of the study were compared with those of an earlier study on cloxacillin in haemodialysis patients. Serum and urine concentrations of flucloxacillin and cloxacillin were determined by bio-assay, and a one-compartment model was used for the calculations. 3 Higher serum concentrations reached after oral administration of flucloxacillin as compared with cloxacillin were based not only on better oral absorption (53.7% and 32.9%, respectively) but also on slower (renal and extra-renal) elimination (T1/2 : 46 and 32 min, respectively). A significant difference between the apparent volumes of distribution of flucloxacillin and cloxacillin, which could contribute to higher serum concentrations, could not be demonstrated. Considerable individual variation occurs in the rate and amount of oral absorption, especially in patients. The elimination rate of flucloxacillin in haemodialysis patients (T1/2 : 2h 53 min) corresponds with the extra-renal elimination rate in healthy subjects. No influence of haemodialysis on the elimination rate constant of flucloxacillin was found; total plasma clearance was, however, slightly but significantly higher during dialysis.

Administration, Oral↗
PubMed1975

Absorption of pivampicillin in postoperative patients.

The absorption of orally administered pivampicillin was studied in nine postoperative patients and compared with that of intravenously administered ampicillin. The absorption of pivampicillin was calculated on the basis of comparison of the areas under the serum concentration curves for both modes of administration. After an oral dose of 700 mg the absorption ranged from 40 to 95% (mean, 60%).

Absorption↗
PubMed1973

Quantitative study on the production and kinetics of mononuclear phagocytes during an acute inflammatory reaction.

The present communication concerns a quantitative study on the production and kinetics of mononuclear phagocytes during an acute inflammatory response as compared with the steady-state condition. During an acute inflammation induced by an intraperitoneal injection of NBCS, the peritoneal macrophages increase 2.5 times and there is a concomitant threefold increase of the monocytes in the peripheral blood. This increase of the peritoneal macrophages could be caused by a local proliferation of these cells or by the recruitment of monocytes from the circulation. The results of the in vitro and pulse-labeling studies demonstrate that the mitotic activity of the peritoneal macrophages is not increased during the inflammatory response, which indicates that the increase in the number of these cells is not due to local proliferation. Evidence is also presented that the small proportion (maximally 4%) of peritoneal macrophages that synthesize DNA are very recently arrived from the circulation. In agreement with this is the finding that a small number (less than 3%) of the peripheral blood monocytes are capable of synthesizing DNA. Since proof was obtained that the macrophages in the inflammatory peritoneal exudate originate from peripheral blood monocytes and the number of these cells in the circulation was also augmented, an increased formation of monocytes in the bone marrow was expected. Because increased monocyte production could be brought about by an increased number of promonocytes and/or an acceleration of the mitotic activity of the promonocytes, the various parameters of the cell cycle of these cells were determined. In normal mice the DNA-synthesis time of the promonocytes was 11.8 h, the cell cycle time 16.2 h, and the G(1) + G(2) + M phases 4.4 h. During the first 12 h of the inflammatory response a significantly shorter DNA-synthesis time (7.6 h) and cell cycle time (10.8 h) was found. At 24 h, these values approximated those found in normal mice. Next, both the total production and the rate of production of the monocytes were calculated and compared for both conditions. This computation showed that the total production of labeled monocytes during the first 48 h of an acute inflammation was 64% greater than in normal mice. The rate of production, calculated in two ways (i.e., from the data of the total production and also from the data of the cell cycle time together with the total number of promonocytes) complemented each other very well. During the first 12 h of the inflammatory response the production rate was increased 1.5 times and then leveled off, reaching almost the normal rate after 24 h. Furthermore, the excellent agreement between the results of the two methods of calculation for the normal steady state confirmed once more that the promonocyte is the direct precursor cell of the monocyte, giving rise to the two monocytes after each division. The kinetics of the monocytes in the peripheral blood was also altered during the inflammatory response. During the first 48 h, twice the normal number of labeled monocytes went from the bone marrow to the peripheral blood and twice the normal number also left the circulation. Furthermore, at least 70% of this increased number of labeled monocytes leaving the circulation migrated into the inflammatory exudate of the peritoneal cavity, leading to a roughly 11-fold increase of labeled peritoneal macrophages.

Animals↗