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Plasmodium berghei infection impaired the hepatic heme synthesizing machinery of mice. Key enzymes, viz. S-aminolevulinic acid synthase, S-aminolevulinic acid dehydrase and ferrochelatase were found to be decreased. In contrast, tryptophane pyrrolase noticeably increased during parasitic infection. Oral feeding of chloroquine [16 mg (kg body weight) −1 × 4 days] cleared the parasitaemia from infected mice within 72 h and returned the altered levels of enzymes almost to normal a week after cessation of treatment, the exception being tryptophane pyrrolase, which remained unaffected. Chloroquine treatment did not cause any significant alteration in the above-mentioned enzymes of normal mice.

The effects of the newly developed antimalarial compound, CDRI 80/53 [ N ′-3-acetyl-4-5-dihydro-2-furanyl)- N 4 -(6-methoxy-8-quinolinyl)1,4-pentane-diamine], and primaquine (PQ) on the antioxidant system of mice were determined at equi-effective antimalarial doses systems responsible for protection against oxygen, i.e. hepatic superoxide dismutase and catalase. While PQ significantly inhibited these enzyme activities CDRI 80/53 did not. However, both compound 80/53 and PQ increased the level of superoxide anion and lipid peroxidation. It is concluded that compound 80/53 has less effect on antioxidant defence enzymes than PQ.

Hexokinase, phosphofructokinase and pyruvate kinase, the regulatory enzymes of the glycolytic sequence, showed progressive increases in their activities with the rise of parasitaemia in Plasmodium knowlesi-infected rhesus monkey serum and red blood cells. Chloroquine therapy cleared the parasitaemia in 72 h and brought the elevated levels of these enzymes back to almost normal in about 30 days.

Dear Sir, With the advent of the Internet, communication and teaching are gradually shifting from the print to the electronic media. The website of the Indian Journal of Radiology and Imaging (IJRI) receives 4000 hits daily.[1] In a study conducted among radiologists in the US, 97% of respondents indicated that they used the Web for education.[2] The setting up and maintenance of websites involves both initial and recurring monetary liabilities. Webgroups are an innovative tool for maintaining an online presence; they have the same basic functionality that full-fledged websites have but do not entail any significant financial burden. We have started a webgroup of the Indian Radiology and Imaging Association (IRIA) - Delhi state branch at the uniform resource locator (URL) http://groups.google.com/group/iriadelhi?lnk=gschg [Figure 1]. Two of the authors (AD and LU) have been chosen as moderators for administering the webgroup. The moderator's job is to approve members who sign up directly at the group's webpage, thus eliminating spam and misuse. All posted messages are screened before being displayed online. The moderators also post details of the monthly or annual meetings of the Delhi chapter of the IRIA and other CME programmes. These posts are emailed automatically to all members apart from being universally accessible at the group webpage. Figure 1 Screen capture of the webpage of the Delhi chapter of the IRIA Google groups is a free webgroup hosting service provided by Google Inc. Disseminating information through a webgroup is fast, entails lower costs than traditional postage, saves stationary, and is eco-friendly. The finances thus saved can be channelized into more productive avenues. Some disadvantages of using a group instead of a regular website include the inability to offer advanced functions such as payment gateways or an online voting system for state body elections. Future directions include posting of interesting cases, online registration for conferences and CMEs, and uploading scientific sessions of CME programs.

Earlier we reported that prophylactic treatment with recombinant human interferon gamma (rHuIFN-gamma) for a prolonged duration completely suppressed experimental infection with Plasmodium cynomolgi B sporozoites in rhesus monkeys. We now show that reducing the rHuIFN-gamma treatment to three administrations given close to the time (on days -1, 0, and +1) of infection was sufficient for complete protection. Animals initially protected by rHuIFN-gamma treatment are susceptible to reinfection. Studies are in progress to understand the precise mechanism of protection afforded by HuIFN-gamma against sporozoite-induced malaria infection.

RESUME L'on a mis a l'essai des boutures de tige de Leucaena leucocephala, Robinia pseudoacacia, Celtis australis, Grewia optiva et Populus deltoides pour voir leur capacite de s'enraciner dans des lits a l'interieur d'une chambre a brumisation avec temperature et humidite reglees. L. leucocephala et P. deltoides s'enracinaient facilement. L'on a reussi a enraciner R. pseudoacacia, C. anstralis et G. optiva, d'habitude difficiles a enraciner, en utilisant des traitements d'auxines differentes. La brisure de la barriere anatomique par une division verticale, avec l'application de regulateurs de croissance (IAA, IBA et NAA) a provoque la formation de racines adventices.

Methemoglobin toxicities of primaquine and compound N1-(3-acetyl-4-5-dihydro-2-furanyl)-N4-(6-methoxy-8-quinolinyl) 1,4-pentanediamine, CDRI Code 80/53, have been compared in beagles. Primaquine administration at 3 mg/kg for 7 days produced significantly high (P less than 0.001) methemoglobinemia and the levels increased 10.55-fold. Compound 80/53 at 3.75 mg/kg x 7 days produced a marginal increase in methemoglobinemia (3.24-fold; P less than 0.02). The methemoglobin formed by primaquine administration was 3.65-fold (P less than 0.001) higher than that formed after administration of compound 80/53. There was no significant change in other hematological parameters and liver function tests.

An analogue of primaquine, N1-(3-acetyl-4-5-dihydro-2-furanyl)-N4-(6-methoxy-8-quinolinyl) 1,4-pentanediamine, CDRI Code 80/53), has been evaluated for anti-relapse activity against sporozoite induced Plasmodium cynomolgi B infection in rhesus monkeys. The compound has shown 100% curative anti-relapse activity at 1.25 mg/kg x 7 day dose schedule, thereby giving a primaquine index of 0.8. The compound is currently under Phase-I clinical trials.

Blood induced Plasmodium berghei infection in Swiss mice was exposed during successive passages to melfloquine alone or melfoquine in combination with dapsone or primaquine or erythromycin, and the level of resistance to melfoquine in four sub-lines was compared at ED90 level. Treatment with mefloquine alone resulted in a 201.14 fold increase in resistance after 21 passages. Use of drug combination (melfoquine + dapsone) delayed the acquisition of resistance as shown by a marginal increase of ED90 by 5.76 fold after 34 passages. Similarly, there was a 17.84 fold increase of resistance after 32 passages involving exposure to mefloquine-primaquine and a 112.28 fold increase after exposure to melfoquine-erythromycin combination for 31 passages. The study emphasizes that rational drug combinations should be developed to protect the melfoquine against the emergence of resistance in P. falciparum cases.

Prophylactic treatment with 0.1 mg of human gamma interferon per kg (body weight) per day completely suppressed experimental infection with Plasmodium cynomolgi B sporozoites in rhesus monkeys. Treatment with lower doses partially suppressed this infection. Prophylactic treatment with human gamma interferon, however, had no protective effect against trophozoite-induced infection, suggesting that the interferon effect was limited to the exoerythrocytic stage of parasitic development.

In 1991 and 1992 studies on Dalbergia sissoo Roxb. showed the availability of ample amount of viable seed from November to May. Viability of seeds collected from December to March was more than 90 per cent. There was a slight but significant decrease in germination from March to may. Again germination per cent was slightly and significantly decreased from May to July. Thereafter, seed availability and viability were got drastically reduced. Sufficient viable seed of Dalbergia sissoo Roxb. can be collected at any time from November to July.

Background Despite the wide spread use of lumefantrine, there is no study reporting the detailed preclinical pharmacokinetics of lumefantrine. For the development of newer anti-malarial combination(s) and selection of better partner drugs, it is long felt need to understand the detailed preclinical pharmacokinetics of lumefantrine in preclinical experimental animal species. The focus of present study is to report bioavailability, pharmacokinetics, dose linearity and permeability of lumefantrine in rats. Methods A single dose of 10, 20 or 40 mg/kg of lumefantrine was given orally to male rats (N = 5 per dose level) to evaluate dose proportionality. In another study, a single intravenous bolus dose of lumefantrine was given to rats (N = 4) at 0.5 mg/kg dose following administration through the lateral tail vein in order to obtain the absolute oral bioavailability and clearance parameters. Blood samples were drawn at predetermined intervals and the concentration of lumefantrine and its metabolite desbutyl-lumefantrine in plasma were determined by partially validated LC-MS/MS method. In-situ permeability study was carried in anaesthetized rats. The concentration of lumefantrine in permeability samples was determined using RP-HPLC. Results For nominal doses increasing in a 1:2:4 proportion, the Cmax and AUC0-∞ values increased in the proportions of 1:0.6:1.5 and 1:0.8:1.8, respectively. For lumefantrine nominal doses increasing in a 1:2:4 proportion, the Cmax and the AUC0-t values for desbutyl-lumefantrine increased in the proportions of 1:1.45:2.57 and 1:1.08:1.87, respectively. After intravenous administration the clearance (Cl) and volume of distribution (Vd) of lumefantrine in rats were 0.03 (± 0.02) L/h/kg and 2.40 (± 0.67) L/kg, respectively. Absolute oral bioavailability of lumefantrine across the tested doses ranged between 4.97% and 11.98%. Lumefantrine showed high permeability (4.37 × 10-5 cm/s) in permeability study. Conclusions The pharmacokinetic parameters of lumefantrine and its metabolite desbutyl-lumefantrine were successfully determined in rats for the first time. Lumefantrine displayed similar pharmacokinetics in the rat as in humans, with multiphasic disposition, low clearance, and a large volume of distribution resulting in a long terminal elimination half-life. The absolute oral bioavailability of lumefantrine was found to be dose dependent. Lumefantrine displayed high permeability in the in-situ permeability study.