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Biomedical subjects

M Slavik

Publications and source records attributed to M Slavik.

At least 55 records · Page 3Linked to original sources
PubMed1984

An individualized plastic intraoral device for the collection of human parotid saliva.

A new individualized, non-invasive device for the collection of parotid saliva is described which offers the following advantages: automatic placement in the proper position for saliva collection by patients without the help of a technician, lack of deadspace, lack of salivary leakage around the device, elimination of cross contamination between patients, and unlimited re-use. Because of its simplicity, it is an ideal device for routine collection of parotid saliva samples in therapeutic drug monitoring, biochemical monitoring of exposure to toxic materials, and detection of secretory component deficiencies of immune system disorders.

Adult↗
PubMed1983

Pharmacokinetic study of methyl glyoxal-bis-guanylhydrazone (methyl-GAG).

Using a paired ion exchange high pressure liquid chromatographic assay, pharmacokinetic evaluation of methyl glyoxal bis guanylhydrazone (methyl-GAG) was performed in nine male New Zealand albino rabbits following administration of a single intravenous bolus dose of 50 mg/kg B.W (550 mg/m2 BSA). Blood samples were collected before and at intervals of 5, 10, 15, 30 min and 1, 2, 3, 4, 6, 8, 12, 18, and 24 h after administration of the drug. The analysis of experimental data indicates a three compartment open model with first order elimination from the central compartment described by the equation Cpt = A.e-alpha t + B.e-beta t + C.e-gamma t, where A, B, C, are 107.985, 4.785, and 0.763 micrograms/ml, respectively. alpha, beta, gamma, are 5.466, 0.487, and 0.030 h-1, respectively, and T1/2 alpha, beta, gamma are 7.6, 85.3 min and 23.1 h, respectively. The mean volume of distribution in the central compartment Vc was 0.44 liters (1)/kg, volume of distribution Vdarea 30.326 1/kg, and the total body clearance 0.9097 1/kg/h. The existence of a long terminal plasma half life of methyl-GAG reported previously in human studies was also confirmed in experimental animals and may explain the cumulative toxicity of this drug.

Animals↗
PubMed1983

Spirogermanium: a new investigational drug of novel structure and lack of bone marrow toxicity.

Spirogermanium (NSC 192965) is a new metallic investigational anticancer drug of novel heterocyclic structure. Although its mode of action has not been fully elucidated, it appears that spirogermanium is not a phase or cell cycle specific drug and inhibits DNA, RNA and protein synthesis, the protein synthesis being the most susceptible to this agent. Spirogermanium has shown cytotoxic activity in vitro against several human tumor cell lines at concentrations (1 micrograms/ml) that were also found toxic to the cultured rat neurons. Although spirogermanium has no effect on normal bone marrow colony forming cells in mice, dogs, or man, it has revealed cytotoxic activity in vitro against human myeloid leukemia cell line K 562 at clinically achievable concentrations. These in vitro findings, indicating selective cytotoxic activity against leukemic cells suggest this drug as a candidate for clinical studies in acute and chronic leukemias. Spirogermanium has revealed activity in vivo against intraperitoneally implanted Walker 256 sarcoma, 13762 mammary adenocarcinoma, and 11095 prostatic carcinoma in rats, but no antitumor activity in vivo was found in the murine tumors used in the past by the NCI screen (L 1210 and P 388 leukemia, B 16 melanoma, Lewis lung carcinoma). Spirogermanium is remarkable for its lack of bone marrow toxicity confirmed in preclinical toxicology and clinical studies; moderate, predictable, and reversible CNS toxicity is dose-limiting. Activity in malignant lymphoma, ovarian cancer, breast cancer, large bowel cancer, and prostatic cancer was reported in the clinical studies. The drug is currently under clinical investigation against the wide spectrum of solid tumors and malignant lymphomas. The dose of 80-120 mg/m2, given by 60' infusion three times a week, is currently used and tolerated in Phase II clinical studies. The recently introduced five days continuous infusion schedule has been also under clinical investigation and the doses of 250-300 mg/m2/day are recommended for Phase II studies. Of interest are results reported in this paper of spirogermanium in vitro preferential activity against the resistant strains of Plasmodium falciparum at clinically achievable concentrations suggesting this drug as a possible new antimalarial agent of novel structure.

Animals↗
PubMed1983

6-azauridine triacetate induced hyper beta-alaninemia and its decrease by administration of pyridoxine.

The effect of pyridoxine on 6-azauridine triacetate (6-AzUrd-TA) induced hyper beta-alaninemia was studied in New Zealand albino rabbits in three experiments. In each of the three experiments the animals were administered by gavage: Group 1 (Control), drinking water; Group 2, 6-AzUrd-TA; and Group 3, 6-AzUrD-TA with pyridoxine. While no beta-alanine was found in the control group or in pretreatment samples of the 6-AZUrd-TA and 6-AzUrd-TA + pyridoxine treated animals, high concentrations of this amino acid (191.0 +/- 91.6, 220.2 +/- 116.3, 103.2 +/- 64.4 nmol/ml) were found on the fourth and seventh days of 6-AzUrd-TA treatment with daily doses of 1.0 g/kg and 0.5 g/kg B.W. respectively. The drug induced hyper beta-alaninemia was significantly (p less than or equal to 0.05) reduced in all three experiments by simultaneous pyridoxine administration in daily doses of 50 mg/kg B. W. These results indicate, that daily repeated oral administration of 6-AzUrd-TA causes elevation of serum beta-alanine, which can be partially prevented by oral administration of pyridoxine. They also indirectly support the hypothesis, that 6-AzUrd-TA induced hyper beta-alaninemia is at least partially caused by the inhibition of beta-alanine degrading enzymes, that use pyridoxal phosphate as a coenzyme. Direct measurement of the enzyme activity is planned in our future studies.

Alanine↗
PubMed1983

Spirogermanium: a new drug with antimalarial activity against chloroquine-resistant Plasmodium falciparum.

Spirogermanium, a new investigational drug of novel structure currently under clinical studies in various neoplastic diseases, has revealed significant in vitro activity against chloroquine-resistant (FCB, FTA, FVO) and sensitive (FSL, FUI, FH) strains of Plasmodium falciparum. Inhibition of the growth and maturation of parasites after 36-h exposures to Spirogermanium started at concentrations ranging from 2.48 to 9.9 nM/ml. These concentrations appear to be within the range of Spirogermanium plasma levels reported in clinical studies with this drug. Since its clinical toxicities are unusually low in comparison with other anticancer drugs, our results on its in vitro activity against Plasmodium falciparum indicate Spirogermanium is an antimalarial drug of entirely novel structure, active in resistant strains.

Antimalarials↗
PubMed1982

Urine levels of N-[9-(beta-D-ribofuranosyl)purin-6-ylcarbamoyl]-L-threonine, N6-(delta 2-isopentenyl)adenosine, and 2'-O-methylguanosine as determined by radioimmunoassay for normal subjects and cancer patients.

Radioimmunoassays (RIA) are presented for the evaluation of the levels of the following three modified nucleosides in human urine: 2'-O-methylguanosine (Gm), N6-(delta 2-isopentenyl)adenosine (i6A), and N-[9-(beta-D-ribofuranosyl)purin-6-ylcarbamoyl]-L-threonine (t6A). Competitive inhibition of the RIA was provided by 2 to 10 microliters of untreated urine and the sensitivity of each RIA was in the pmol range. Partial fractionation of urine indicated that the majority of inhibitory activity was in the fraction coeluting with a nucleoside standard. The amounts of nucleosides in 24-hr urine samples from eight normal subjects were 2.2 +/- 0.9 mg (S.D.) for t6A; 0.17 +/- 0.09 mg for Gm; and 0.050 +/- 0.019 mg for i6A. The levels of t6A, i6A, and Gm were also determined by RIA of urine samples of patients with lymphomas or solid tumors. Levels of t6A were significantly elevated for patients with lung cancer (p less than 0.001), non-Hodgkin's lymphoma (p less than 0.05), and other solid tumors (p less than 0.02) but not for patients with Hodgkin's disease. The RIA data on the other two nucleosides, i6A and Gm, showed no similarly significant variations. Increased levels of t6A in the cancerous state were substantiated by isolating the t6A fraction from the urine of normal subjects of patients with lung cancer and quantitating the amount by use of UV adsorption. These preliminary results indicate that RIA for t6A might be clinically useful by providing a complementary approach to the assessment of the levels of modified nucleosides by gas-liquid or high-performance-liquid chromatography.

Adenosine↗
PubMed1980

Phase I clinical studies with WR-2721.

Toxicity studies of S-2-(3 aminopropylamino)-ethylphosphorothioic acid (WR-2721) access patients in remission following radiation therapy. The dose has been escalated from 25 to 250 mg/m2 without significant symptoms. Inconsistent variation in the systolic blood pressure in some patients has been observed over an 8-10-point range without producing any symptoms. The variation could be within the patient's normal range. However, tests are planned to rule out cardiac toxicity or peripheral vascular reaction. Combining WR-2721 with conventional radiotherapy is contemplated by intravenous injection of the drug 20-30 minutes before irradiation. This will start as weekly injections, and the number of weekly injections will be increased progressively. Animal studies suggest that the level already safely reached could give significant protection to the normal tissues without protecting tumor.

Amifostine↗
PubMed1980

An age-related coagulation disorder associated with experimental infection with infectious bursal disease virus.

Specific-pathogen-free White Leghorn chickens were inoculated with a field strain of infectious bursal disease virus. One group (A) was inoculated at 17 days after the chicks were hatched, and the other groups (C and E) were inoculated at posthatch day 42. Blood samples were obtained for determination of clotting times (whole blood recalcification, prothrombin, and activated partial thromboplastin times), virus-neutralizing antibody, and total hemolytic complement. There were significant increases in clotting times for groups C and E at 3 and 5 days after they were inoculated. There were no significant increases in clotting times at 3 days after inoculation in the group A chickens (inoculated at 17 days after hatching). There were no significant decreases in total complement activity in any of these chickens (groups A, C, and E). This study indicates that the mortality and clinical symptoms observed in chickens experimentally infected with infectious bursal disease virus may be associated with a clotting abnormality because it was noted only in chickens that developed severe clinical disease (inoculated at 42 days after hatching) and was not noted in chickens that remained clinically normal (inoculated at 17 days).

Age Factors↗
PubMed1979

[Comments on the problem of differential diagnosis of tumours of the nerve sheaths in angiography (author's transl)].

The article describes the special features governing the assessment of angiographic findings in tumours of the nerve sheaths. Considerations of differential diagnosis, especially between neurinoma and neurofibroma, are discussed. Likewise, the problems of differential diagnosis of such tumours against neoplasms of the tissue of the soft parts, are also discussed. Angiography permits only a limited determination of the degree of malignancy of the neurinoma and neurofibroma. It is always mandatory to correlate these findings with the histological findings. However, angiography does seem to be justified as an additional examination technique, since it supplies fundamental pointers for surgery.

Adolescent↗
PubMed1979

Changes in amino acid metabolism caused by 6-azauridine triacetate: relevance to cancer treatment.

6-Azauridine triacetate (6-AzUrd-TA) administration causes changes in amino acid metabolism both in experimental animals and in man. This effect is dose-related. Amino acid changes caused by 6-AzUrd-TA resemble those in inborn homocystinuria, beta-alaninemia, and hyperhistidinemia. Inhibition of certain enzymes using pyridoxal phosphate as a coenzyme appears to be the common denominator for these changes. There is supportive evidence suggesting that homocystinemia and thrombotic episodes, both caused by 6-AzUrd-TA, are related. These results also reveal that anticancer drugs other than amino acid analogs and amino acid-depleting enzymes may cause significant changes in amino acid metabolism. Their detection and correlation with the therapeutic or adverse effects can be used as an alternative method for studying the relevance of amino acid changes to the treatment of cancer.

Amino Acids↗