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Biomedical subjects

S M Ibrahim

Publications and source records attributed to S M Ibrahim.

36 records · Page 2Linked to original sources

Synergistic effect of 4-hydroperoxycyclophosphamide and etoposide on a human promyelocytic leukemia cell line (HL-60) demonstrated by computer analysis.

Autologous stem cell transplantation using cryopreserved bone marrow offers the opportunity to rescue patients from hematopoietic toxicity caused by intensive chemotherapy. This approach is potentially useful for high-risk leukemias as well as for other cancers. The development of suitable methods for purging malignant cells from the bone marrow will offer a better chance of success for autologous stem cell transplantation. In this paper, we describe our efforts at purging myeloid cells. HL-60, a promyelocytic leukemia cell line, was used as a model. 4-Hydroperoxycyclophosphamide (4-HC) and VP-16-213 (VP-16) (either alone or in combination) were used to treat HL-60 cells and normal bone marrow. The cytotoxic effect of 4-HC (29.2 micrograms/ml; 100 microM) upon the HL-60 cell line was 99.8 +/- 0.12% (SE), and the colony-forming units-granulocyte, macrophage (CFU-cs) of normal bone marrow was inhibited by 82.5%. VP-16, at a concentration of 25 micrograms/ml (42.5 microM), can kill 99% of HL-60 cells and inhibit 72.7% of the CFU-cs. A drug mixture containing 4-HC (29.2 micrograms/ml) and VP-16 (10 micrograms/ml) (combination ratio, 1:0.342) reduces HL-60 cells to an undetectable number, and the CFU-cs were inhibited by 87.2%. The laboratory data were further analyzed for the synergistic effect of these two drugs by quantitative determination of the median effect plot and the multiple drug equation recently described by Chou and Talalay (Adv. Enz. Regul., 22: 27-55, 1984). Interactions of two drugs at different effect levels and at different combination ratios were then determined by computer simulation. At high effect levels, 4-HC and VP-16 in combination gave a synergistic cytocidal effect on HL-60 leukemic cells and gave an antagonistic inhibitory effect on normal bone marrow CFU-cs. This combination greatly increases the safety margin. Computer simulation of a dose effect relationship has also shown that the 4-HC:VP-16 combination ratio of 1:0.342 yields a better selective effect than a ratio of 1:0.856. This quantitative analysis suggests that the combination of these two drugs at the selected dose level offers a good method for purging nonlymphoblastic leukemia cells.

Antineoplastic Combined Chemotherapy Protocols↗

Schistosoma mansoni (Gezira) infection in Biomphalaria pfeifferi snails from Gezira and Jebel Marra.

The comparative susceptibility of Biomphalaria snails from Gezira and Jebel Marra to S. mansoni (Gezira) was investigated. Groups of laboratory-bred snails from the two localities were exposed to 0, 1, 2, 3 and 4 miracidia. The growth rate of the snails was followed over the experimental period by measuring the snails' shell size. Sub-groups of infected snails were examined for daughter sporocyst counts by crushing of the snails. Other groups of exposed snails were maintained until cercariae were shed. The exposed snails grew faster than the controls and growth was not dependent on the number of infecting miracidia. Jebel Marra snails grew faster than the Gezira snails and development of the daughter sporocysts within the snails was temperature dependent. Daughter sporocysts were first found on day 19 after exposure when the laboratory temperature ranged between 18 and 25 degrees C and on day 10 at a range of between 28 and 30 degrees C. Daughter sporocysts and cercarial counts overlapped in numbers per snail exposed to 1, 2, 3 and 4 miracidia for both Gezira and Jebel Marra snails. Nine out of 78 Jebel Marra snails were negative for daughter sporocysts, while all of the Gezira snails were positive. This might indicate greater susceptibility of the Jebel Marra snails to the parasite. Our experiments showed that snails from Jebel Marra are capable of supporting an S. mansoni infection from the Gezira until cercariae are shed. The epidemiological significance of the migrant labourers to the Gezira area in the transmission and spread of intestinal schistosomiasis in Jebel Marra is discussed.

Animals↗

Electrocardiographic changes after ethanol and methanol administration in albino rats.

As an acute effect, both ethanol and methanol prolong P-R, Q-T and ST intervals in rat electrocardiogram. The R wave amplitude showed a marked increase with methanol. Other ECG abnormalities like S-T segment changes, appearance of Iso-electric S-T segment, inverted 'T' wave, ventricular ectopic and wandering pace maker were more common in methanol treated animals.

Animals↗