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Biomedical subjects

B G Schuster

Publications and source records attributed to B G Schuster.

27 records · Page 2Linked to original sources
PubMed1994

Antimalarial activity of WR 243251, a Dihydroacridinedione.

WR 243251 is a dihydroacridinedione that was evaluated for antimalarial blood schizonticidal activity in vitro and in vivo. The in vitro doses calculated to kill 50% of organisms were 11 nM for a chloroquine-susceptible, mefloquine-resistant standard strain and 25 nM for a chloroquine- and pyrimethamine-resistant standard strain. The total dose needed to cure 100% of mice infected with a drug-susceptible strain of Plasmodium berghei was 12 to 20 mg/kg of body weight for both oral and subcutaneous administration. The regimen needed to cure 100% of Aotus monkeys infected with Plasmodium falciparum was 8 mg/kg/day for 3 days (chloroquine-susceptible strain) and 16 mg/kg/day for 3 days (chloroquine-resistant strain). The 100% curative doses for Aotus monkeys did not increase for parasites previously exposed to subcurative doses. The absolute value of the curative doses of WR 243251 was comparable to or lower than the values for clinical antimalarial agents. The high absolute activity, comparability of activities against susceptible and resistant parasites, and inability to induce resistance by exposure to subcurative doses suggest that WR 243251 has strong potential as a blood schizonticidal agent.

Acridines↗
PubMed1994

Efficacy of azithromycin as a causal prophylactic agent against murine malaria.

The efficacy of the newly marketed azalide azithromycin was compared with that of the clinical agent doxycycline in a murine model of sporozoite-induced malaria. Drug was administered once; Plasmodium yoelii sporozoites were administered 2 h later; survival at day 60 was determined. For parenterally administered drug, 160 mg of azithromycin or doxycycline per kg of body weight was 100% effective; 40 mg of azithromycin per kg was 80% effective, but 40 mg of doxycycline per kg was 40% effective. Orally administered azithromycin was somewhat less effective than parenterally administered drug, consistent with the 37% clinical oral bioavailability of this agent. For orally administered azithromycin, 160 mg/kg was 100% effective and 40 mg/kg was 40% effective. The efficacy of azithromycin in comparison with that of doxycycline and the known prolonged levels of azithromycin in the livers of humans suggest that azithromycin has potential as a clinical causal prophylactic agent for malaria.

Animals↗
PubMed1994

Fatal neurotoxicity of arteether and artemether.

Artemisinin (qinghaosu) and several derivatives have been developed and are in use as antimalarial drugs but scant information is available regarding animal or human toxicity. Following a eight-day, multiple-dose, pharmacokinetic study of arteether (AE) (10 mg/kg/day [n = 6] and 20 mg/kg/day [n = 6]) in dogs, all high-dose animals displayed a progressive syndrome of clinical neurologic defects with progressive cardiorespiratory collapse and death in five of six animals. Neurologic findings included gait disturbances, loss of spinal and pain response reflexes, and prominent loss of brain stem and eye reflexes. Animals had prolongation of QT interval corrected for rate (QTc) on electrocardiograms (ECGs) with bizarre ST-T segment changes. Prominent neuropathic lesions were noted to be primarily limited to the pons and medulla. Similar lesions with dose-related severity were noted in eight other dogs studied in a second study with intramuscular (IM) administration of AE in sesame oil during a 28-day, dose-ranging study using 5, 10, 15, and 20 mg/kg/day. Injury, graded by a pathologist blinded to the dose group, showed a dose-related, region-specific injury in all animals that was most pronounced in the pons. Further studies in Sprague-Dawley rats using IM administration of AE and artemether (AM) at a dose of 12.5-50 mg/kg/day for 28 days confirmed the onset of a clinical neurologic syndrome with dose-related changes in body weight, activity, and seizure-like activity, stereotypic movement disorders, and ECG changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Reduced resources applied to antimalarial drug development.

This statement was made in 1984 (Ref. I): 'The Agency for International Development (AID) announced a major breakthrough in the development of a vaccine against the most deadly form of malaria in human beings. The vaccine should be ready for use around the world, especially in developing countries, within five years.' Since then, the spending on development of drugs against malaria has been on the decline. Brian Schuster and Wilbur Milhous wonder. did we declare victory too soon? Wouldn't the prudent approach have been to look at vaccines and drugs as complementary techniques rather than alternative approaches?

Journal Article↗
PubMed1993

Comparison of beta-artemether and beta-arteether against malaria parasites in vitro and in vivo.

The antimalarial activity of beta-artemether and beta-arteether was compared in three test systems: in vitro against chloroquine-resistant and chloroquine-sensitive Plasmodium falciparum parasites, in mice infected with P. berghei, and in Aotus monkeys infected with chloroquine-resistant P. falciparum. In vitro, the mean 50% inhibitory concentration (IC50) for beta-artemether was 1.74 nM (range 1.34-1.81 nM), and this value for beta-arteether was 1.61 nM (range 1.57-1.92 nM). They were approximately 2.5-fold more potent than artemisinin, which had a mean IC50 of 4.11 nM (range 3.36-4.60 nM). In the mouse model, the 50% curative doses (CD50) of beta-artemether and beta-arteether had a mean value of 55 mg/kg (32-78 mg/kg). The 50% effective curative doses (ED50) in the Aotus monkey were 7.1 mg/kg (95% confidence interval [CI] = 3.7-13.5) for beta-artemether and 11.8 mg/kg (95% CI = 6.5-21.3) for beta-arteether. Overall, the activities of the two drugs were comparable.

Animals↗
PubMed1979

A new method for in-place testing of tandem HEPA filter installations.

A new in-place high-efficiency particulate air (HEPA) filter testing procedure has been developed, based on the use of an intracavity laser particle spectrometer for ultrasensitive detection of challenge particulate concentrations downstream of tandem HEPA filter installations. The feasibility of these measurements had initially been demonstrated on a small-scale laboratory system where overall protection factors of 10(9) were routinely measured. The primary scaling problem for systems up to 20 000 CFM was in producing sufficient challenge aerosol. This was accomplished by the design and construction of a high-volume thermal dioctyl phthalate generator. The results of acceptance testing of 13 tandem HEPA filter systems, performed with both the spectrometer technique and conventional light-scattering photometry, are displayed and problem areas discussed.

Air↗
PubMed1978

Tandem HEPA filter tests.

Current methods for evaluating the performance and reliability of high-efficiency air cleaning systems use forward light-scattering photometers and DOP aerosol. This method is limited to measuring protection factors of 10(4) or 10(5) and has poor sensitivity to particles less than .3 micron. More accurate determination of system performance could be made by measuring two filter stages with a single test. Because of the large protection factors of a two-stage system, it is necessary to use high challenge aerosol concentrations and long downstream sampling times. Concentrations were measured using an intra-cavity laser light-scattering aerosol spectrometer which is capable of detection of single particles ranging in size from 0.07 to 3.00 micron diameter. The results of several tests with challenge aerosols of both NaCl and DOP yielded protection factors ranging from 1.4 x 10(7) to 3.0 x 10(9) for two HEPA filters in series.

Aerosols↗