Effect of alpha,beta-arteether against primary amoebic meningoencephalitis in Swiss mice.

Artemisinin and its derivative alpha, beta-arteether have been evaluated for activity against experimental primary amoebic meningoencephalitis. In vivo experiments have shown that amphotericin B at dose of 2.5 mg/kg for 5 days produced 100% protection. Artemisinin and alpha, beta-arteether, even when tested at a high doses (60-120 mg/kg x 5 days and 90-180 mg/x 5 days) respectively, were not curative and showed only slight protection as indicated by extension of mean survival time.

Histochemical changes in host tissues from Plasmodium cynomolgi B infected rhesus monkey (Macaca mulatta).

Plasmodium cynomolgi B has been used to infect the rhesus monkey to study the histochemical changes (lipid infiltration, glycogen, protein, DNA and RNA) in liver, kidney and spleen during early (exoerythrocytic) and late (chronic) stages of malarial infection. Infected liver showed significant lipid infiltration during exoerythrocytic and erythrocytic (acute phase) stage of infection. Kidney showed lipid deposition during acute phase of infection while spleen sections were negative for lipid depositions. As a result of malarial infection there was significant depletion of glycogen in liver during exoerythrocytic stage of infection. Glycogen content increased in liver and kidney during erythrocytic stage of infection. The spleen which is the main target of immunopathology in malaria showed no change in glycogen content. During exoerythrocytic phase host tissue organs showed no change in protein and nucleic acids while erythrocytic phase showed slightly increased proteins in liver and kidney. Nucleic acids became decreased in liver and spleen during erythrocytic phase of infection. The parasite used in this study has a defined prepatent period, can be cyclically passaged with ease and non fatal in nature.

Comparative evaluation of blood schizontocidal activity of quinine and quinidine against drug resistant rodent malaria.

Blood schizontocidal activity of quinine and quinidine has been compared against sensitive as well as chloroquine/mefloquine/quinine resistant strains of Plasmodium berghei and a multiple resistant strain of P. yoelii nigeriensis in Swiss mice. Evaluation of results on ED50/ED90 basis has shown distinct superiority of quinidine over quinine against sensitive as well as drug resistant strain of rodent malaria.

Pattern of relapses in sporozoite induced Plasmodium cynomolgi B infection in rhesus monkeys.

The pattern of sequential relapses in 10 rhesus monkeys following inoculation of sporozoites of Plasmodium cynomolgi B has been studied after administering curative dose of chloroquine (5 mg/kg base X 7 days) to eliminate blood parasitaemia after each relapse. Observation for periods ranging from 109 to 245 days showed that the interval between first six relapses was 19.3 +/- 6.77 days (1st relapse), 20.9 +/- 8.43 days (2nd relapse), 22.8 +/- 8.55 days (3rd relapse), 27.8 +/- 10.0 days (4th relapse), 31.67 +/- 11.50 days (5th relapse) and 32.5 +/- 16.26 days (6th relapse). The results of this study indicate a gradual extension of the relapse interval in successive relapses.

Causal prophylactic activity of a new 8-aminoquinoline derivative against Plasmodium cynomolgi B in rhesus monkeys.

A new 8-aminoquinoline derivative, N1-(3-acetyl-4-5-dihydro-2 furanyl)-N4-(6-methoxy-8-quinolinyl)1,4-pentanediamine, synthesized at CDRI, Lucknow, showed causal prophylactic activity at 3.16 mg/kg x 3 doses (on day -1, 0 and +1) against sporozoite induced P. cynomolgi B infection in rhesus monkeys. Single dose of 10 mg/kg of this compound on day 0 also prevented establishment of patient infection. Activity of the compound was comparable to that of primaquine (with causal prophylactic activity at 1.78 mg/kg in three day test and at 10.0 mg/kg in single dose test).

Study on blood level of human placental lactogen in abnormal pregnancy.

The hormone human placental lactogen (HPL) was measured in 15 expectant mothers with pre-eclamptic toxaemia, 5 with postdated pregnancy and 2 mothers with intrauterine growth retardation (IUGR). These levels were compared with that of 43 expectant mothers without any complications. In preeclamptic toxaemia (PET), HPL showed higher or normal values but in severe cases of PET and in those with proteinuria, hormone level was depressed as compared to normal pregnancy. Also in younger mothers (22 years or less) with the complication, the hormone level was low, though no relation with parity was observed. In case of IUGR, the hormone level was within the normal range although one pregnancy ended in intra-uterine foetal death. Low level of the hormone was found in pregnancies ending in low birth weight babies and in postdated pregnancies with foetal postmaturity syndrome.

Effect of a new 8-aminoquinoline antimalarial compound on hepatic microsomal mixed function oxidase system of mice.

A new 8-aminoquinoline derivative (compound 80/53) synthesized at the Central Drug Research Institute, Lucknow (India), has been found to be an active anti-relapse (tissue schizontocidal) compound. Compound 80/53 at 8.75 mg/kg x 4 days and primaquine at 7.00 mg/kg (base) x 4 days given orally to Swiss mice led to inhibition of the different components of the hepatic microsomal mixed function oxidase system to varying degrees. Compound 80/53 inhibited cytochrome P-450, aminopyrine-N-demethylase, aniline and benzo (a) pyrene hydroxylase, cytochrome b5 and heme content of the normal mice by 12, 14, 0, 57, 20 and 6 per cent respectively, whereas the inhibition caused by primaquine in these components was 25, 21, 17, 48, 26 and 6 per cent respectively. Thus, there was less inhibition of hepatic microsomal MFO system of mice by compound 80/53 as compared to that by primaquine.