Biomedical subjects
D Platt
Publications and source records attributed to D Platt.
[The phagocytosis activity of India ink in the isolated rat liver perfused with piracetam].
The activity of the reticulohistiocytic system of the isolated perfused liver was measured under the influence of piracetam (Nootrop). Also the parameters of liver function under the influence of piracetam were determined. If the energetical properties were not optimal it was shown that the phagocytic activity increased under the influence of piracetam. Also the parameters of liver cell function increased. Under optimal energetic properties there was no changing of the phagocytic activity but the liver cell parameters decreased.
The effect of age on clinical pharmacokinetics of piracetam.
In this study the pharmacokinetics of 2-oxopyrrolidine-1-acetamide (piracetam, Nootrop), were studied in 10 geriatric patients with multiple diseases aged between 69 and 87 years. After intravenous administration of 6 g piracetam, the concentration of the drug in plasma was measured after 5, 10, 15 and 30 min as well as after 1, 2, 4, 6, 8, 10, 12 and 24 h. An analysis of laboratory diagnostic findings was carried out in parallel. The kinetic parameters were correlated with the laboratory diagnostic data and discussed together with the currently available results in the literature. The finding which seems to be of particular significance is that multimorbidity is a more important factor influencing the pharmacokinetics than age.
Determination of 3,7-dimethyl-1-(5-oxohexyl)-xanthine (pentoxifylline) and its 3,7-dimethyl-1-(5-hydroxyhexyl)-xanthine metabolite in the plasma of patients with multiple diseases using high-performance liquid chromatography.
Pharmacokinetic studies of pentoxifylline in elderly patients with multiple diseases are described. Because of the low plasma levels of pentoxifylline and its hydroxy metabolite a new high-performance liquid chromatographic method was established. Under our chromatographic conditions, piracetam, a nootropic drug, can be easily separated from simultaneously applied pentoxifylline and its metabolite. Piracetam shows no appreciable ultraviolet absorption above 230 nm and cannot be detected at 268 nm.
The influence of age and multimorbidity on the pharmacokinetics and metabolism of spironolactone.
The pharmacokinetics of the metabolites of spironolactone (canrenone and fluorigenic metabolites) were investigated in 10 geriatric female patients with multimorbidity after a multiple daily oral administration of 100 mg spironolactone under steady state conditions. The concentration determinations were carried out simultaneously with a specific HPLC method and a less specific fluorimetric method. On comparison of the pharmacokinetic parameters with the respective values of a control group of younger healthy female subjects, the serum concentrations in the elderly patients were found to be twice as high. In addition, a statistically significant positive correlation with age was found in the patients for the kinetic parameters investigated. A positive correlation existed between erythrocyte count and the pharmacokinetic parameters of canrenone, especially with the area under the concentration/time curve. No such association was detectable, however, for the total fraction of fluorigenic metabolites (including canrenone). The results of our investigation indicate that, in addition to the known high binding of canrenone to plasma proteins, there is also possibly a (restrictive) binding to erythrocytes.
Use of lipids to potentiate the antibacterial activity of aminoglycosides.
Linolenyl alcohol has been shown to inhibit the in vitro growth of several species of gram-positive bacteria. Since the double bonds in linolenyl alcohol could undergo autooxidation, the antimicrobial activities of saturated primary alcohols of similar molecular sizes against Streptococcus mutans BHT were evaluated. Tridecan-1-ol was identified as the most active compound, eliciting a bacteriostatic effect at concentrations at which growth occurred in the presence of other saturated alcohols or linolenyl alcohol. Evidence is also presented that the combined use of tridecan-1-ol and gentamicin sulfate produces a synergistic effect that is bactericidal to S. mutans BHT. A similar bactericidal response was observed when tridecan-1-ol was combined with other aminoglycosides or tested alone against other strains of S. mutans.
[Significance of experimental gerontology for modern geriatrics].
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[Drug incompatibility in the aged].
Geriatric patients often have several diseases so that in the acute phase the doctor has to treat with many drugs simultaneously. Elderly persons are more vulnerable to drug effects, both therapeutic and adverse. Physiological and pathological changes with aging influence geriatric drug therapy. Pharmacokinetic differences are generally consistent with age differences in renal and liver function, body composition, tissue perfusions, protein and cellular binding. The present paper gives some examples (glycosides, anticoagulants) of drug therapy and adverse reactions.
[Age dependent changes in organs and the significance for drug therapy].
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[Phagocytosis activity of the isolated perfused rat liver].
The reticulohistiocytary system was tested with colloidal carbon. Isolated livers were perfused at 20 degrees C, 28 degrees C, 37 degrees C and 45 degrees C with a hemoglobin and protein free medium. It was shown that the perfusion at 28 degrees C revealed a significantly better phagocytosis as at temperatures of 37 degrees C and 45 degrees C. The control parameters of the liver function got, gpt lactate-pyruvate, beta-hydroxybutyrate and acetoacetate displayed the best results at 28 degrees C.
Age dependent phagocytosis of red cell membranes by the reticulohistiocytary system of the isolated perfused rat liver.
Isolated rat livers were perfused with a medium free of immune globulines, protein and hemoglobin to investigate age-dependent differences in the phagocytosis of erythrocyte membranes. Membranes of young erythrocytes were phagocytised in a significantly higher rate than those of old ones. The control parameters of the liver function were also significantly higher during the increased phagocytosis of the young cells than that of old cells and cells of the control group.
Naturally occurring cell-mediated cytotoxicity against simian virus 40-transformed 3T3 murine tumor cells.
The tumorigenicity and host protective mechanisms induced by simian virus 40 (SV40)-transformed 3T3 cells (SV403T3) were evaluated in syngeneic BALB/c mice. Tumors were regularly produced by sc inoculation of SV403T3 cells; the incidence, latent period, and survival were proportional to the size of the initial inoculum. With the use of an in vitro 18-hour 51Cr cytotoxicity assay, spleen cells from normal mice showed a dose-related killing activity against the SV403T3 cells. At an effector cell-to-target cell ratio of 200:1, the average lysis was 56 +/- 6%. This reaction appeared specific for the virally transformed targets; the mean lysis of parent 3T3 cells was 23 +/- 5%. Effectors were resistant to anti-theta serum and not removed by adherence to plastic or nylon wool. Tissue distribution studies indicated that these effectors were present in high concentrations in spleen, bone marrow, lymph nodes, and peritoneal cavity. Low levels of activity were associated with cells from the thymus. In the present studies specific T-cell cytotoxicity against the SV403T3 cells could not be demonstrated. Animals challenged with nonviable SV403T3 cells prior to tumor cell inoculation did not show increased in vivo resistance. In parallel, the in vitro cytotoxicity of animals inoculated with SV403T3 tumor cells showed no heightened cell killing compared to the cytotoxicity of normal controls.
[Elimination of desacetyl cefotaxime in geriatric patients with multiple diseases].
Plasma concentrations of cefotaxime and desacetyl cefotaxime were determined by HPLC in geriatric patients with multiple diseases. Comparison with a younger control group of healthy volunteers showed a prolongation of half-life of CTX and dCTX in the older patients. A significant correlation between pharmacokinetic parameters of dCTX and other clinical and chemical parameters was found. Half-life of dCTX was positively correlated with age of the geriatric patients (P less than 0.05). There was also a significant relationship between CHE in serum and plasma peak concentrations of dCTX. Time until reaching plasma peak concentrations correlated closely with total bilirubin (P less than 0.01), CHE (P less than 0.001), cholesterol (P less than 0.01), and urea (P less than 0.01). Accumulation of the pharmacologically active metabolite dCTX could not be excluded in one patient with kidney disease. In accordance with other investigators it is recommended to reduce the dose of cefotaxime in geriatric patients with kidney diseases.
Determination of 2-oxo-pyrrolidine-1-acetamide (piracetam) in human plasma using high-performance liquid chromatography.
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[Parenteral feeding of elderly patients].
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[Cefotaxime. Pharmacokinetics in geriatric patients with multimorbidity].
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