[Ca++ ion transport blockers as reversants of the drug resistance of malarial parasites. 2. The effect of praziquantel on the resistance to chloroquine and compound R-70-Zh of Plasmodium berghei]. / Blokatory transporta ionov Ca++ kak reversanty lekarstvennoi ustoichivosti maliariinykh parazitov. Soobshchenie 2. Vliianie prazikvantelia na ustoichivost' k khlorokhinu i soedineniiu R-70-Zh u Plasmodium berghei.

The reversing action of anthelminthic praziquantel (P) on the effect of chloroquine (C) and compound R-70-Zh (styrylquinazoline) was revealed on a Plasmodium berghei model (white inbred mice), using a LNK65 isolate with naturally reduced sensitivity to chloroquine and its polyresistant line LNK65CHLFR with acquired resistance to chloroquine/fansidar (selected in our laboratory). P (125 mg/kg) in combination with C showed a potentiating effect not only on the LNK65 isolate, but also on the LNK65CHLFR line, while investigated separately on this line, both drugs were not effective in tested doses. Moreover, the similar effect of C on the LNK65CHLFR line was achieved in the dose that was 4 times higher than that of P/C combination. P in a standard dose on the LNK65 isolate showed a more marked activation of compound R-70-Zh that on C. The potentiating effect was manifested in combination with R-70-Zh in the dose half as high as that of C; this phenomenon was also reflected by the efficiency index (5.0 against the 4.0) accepted in our laboratory and may be associated with the higher sensitivity of the LNK65 isolate to R-70-Zh. P showed some antimalarial action which manifested itself only by morphological changes on P. berghei parasites similar to those observed under the action of some dihydropholate reductase inhibitors, such as pyrimethamine.

[Ca++ ion transport blockers as reversants of the drug resistance of malarial parasites. 1. The effect of verapamil on the resistance to chloroquine in vivo of Plasmodium berghei and in vitro of Plasmodium falciparum]. / Blokatory transporta ionov Ca++, kak reversanty lekarstvennoi ustoichivosti maliariinykh parazitov. Soobshchenie 1. Vliianie verapamila na ustoichivost' k khlorokhinu in vivo u Plasmodium berghei i in vitro u Plasmodium falciparum.

The reversing action of verapamil on the effect of chloroquine was found in in vivo experiments by using a model P. berghei resistant to chloroquine, an LNK65 isolate having a naturally lower resistance to the agent, and its polyresistant strain with the acquired resistance to chloroquine and fansidar, as well as by employing the chlorine-resistant P. falciparum isolates from the south of the Socialist Republic of Vietnam. The magnitude of this effect was related to the dose of verapamil, the frequency of administration of a combination of the agents in vivo, while that was associated to the concentration of verapamil and the level of isolate resistance to chloroquine in vitro which was the most pronounced. Taking into account the dose-dependent effect of verapamil, it can be suggested that increasing its concentration in combination with chloroquine can provide a more marked reversing action with lower chloroquine concentrations. The parameters accepted by the authors in evaluating the combined effect enable the effect of the verapamil/chloroquine concentration to be regarded as potentiation.

[The search for new antiparasitic agents. 10. The synthesis, toxicological and antimalarial properties of nitrogen-containing heterocycles with a 4-(4-alkylpiperazinyl-1) phenylamine substituent (the preparation quinoprazine)]. / Izyskanie novykh protivoparazitarnykh sredstv. 10. Sintez, toksikologicheskkie i protivomaliariinye svoistva nekotorykh azotsoderzhashchikh geterotsiklov s 4-(4-alkilpiperazinil-1)fenilaminnym zamestitelem (preparat khinoprazin).

Synthesis is described and acute toxicity and antimalaria action is studied in new derivatives of quinoline and benzo(g)quinoline containing a 4-(4-alkylpiperazinyl-1)phenylamine substitute. Only the derivatives of benzo(g)quinoline were found to have a high antimalaria effect and to have advantages over the standard agent chloroquine on their tolerance and protective action. One of the compounds, 4-[4-(4-ethylpiperazinyl-1)phenylamino] benzo(g)quinoline, named QUINOPRAZINE, showed some action against Plasmodium berghei chloroquine--resistant infection (isolate LN-K65). This agent was elected for further tests.

[The computer processing of experimental research data on malaria. 1. The primary processing of the dynamic indices of malarial infection]. / Komp'iuternaia obrabotka dannykh éksperimental'nykh issledovanii po maliarii. Soobshchenie 1. Pervichnaia obrabotka pokazatelei dinamiki maliariinoi infektsii.

Universal computer software for primary statistical and graphic analysis of data on malaria dynamics in patients and in the experiment has been suggested. The analysis of the results of investigations on rodent malaria model in based on graded parasitemia assessment according to Moshkovskii [correction of Mashkovsky].

[An experimental study of the effect of different biologically active substances on the susceptibility of mosquitoes to the causative agent of malaria. 1. Insect development regulators]. / Eksperimental'noe izuchenie vliianiia razlichnykh biologicheski aktivnykh veshchestv na vospriimchivost' komarov k vozbuditeliu maliarii. Soobshchenie 1. Reguliatory razvitiia nasekomykh.

It has been shown on the model pair Ae. aegypti-P. gallinaceum that dimilin, an inhibitor of insect chitin synthesis has practically no effect on female sensitivity to malaria agent. An analogue of the juvenile hormone juvemon at a concentration of 0.001-0.002 mg/l, causing death of 35% of insects, produces a 7-17% decrease in sporozoite index value. In concentration of 0.004-0.05 mg/l, there is a tendency towards an increase in the vector capacity of the survived female individuals. No differences in the intensity of infection have been revealed between test and control female individuals. No noticeable inhibition of the physiological conditions of test female individuals determined by the following parameters: activity of their aggression towards the donor and their death before and alter the infective feeding have been observed. Thus, none of the substances tested is an inhibitor of the development of malaria plasmodia and their vectors.

[The modelling of the multiple drug resistance of the malarial parasites. 1. The combined resistance of Plasmodium berghei to chloroquine and fansidar]. / Modelirovanie mnozhestvennoi lekarstvennoi ustoichivosti maliariinykh parazitov. Soobshchenie 1. Sochetannaia ustoichivost' Plasmodium berghei k khlorokhinu i fansidaru.

Using a recurrent technique, P. berghei isolate resistant to chloroquine-fansidar combination is formed in golden hamsters. The isolate resistant to chloroquine-fansidar combination was 4 times less sensitive to chloroquine, 2 times less sensitive to fansidar and its combinations, 2 times less sensitive to sulfadoxine, 31 times less sensitive to pyrimethamine, as compared to the baseline isolate LNK65 P. berghei characterized by naturally reduced sensitivity to chloroquine.

[The efficacy of and tolerance for fansimef in the treatment of tropical malaria in the south of the Socialist Republic of Vietnam]. / Effektivnost' i perenosimost' fansimefa pri lechenii tropicheskoi maliarii na iuge SRV.

The efficacy of and tolerance to fancimef in 49 patients was compared to the efficacy of and tolerance to quinine in combination with fansidar in 33 patients with moderate P. falciparum malaria. A good tolerance to and a high efficacy of fancimef have been shown, which was manifested in rapid fever arrest, disappearance of parasitemia, absence of the disease relapses, which were observed in 2 patients on quinine combined with fansidar. The advantage of fansimef is one-time administration of the total course dose.

[The absence of an action of the pyrethroids deltamethrin and cypermethrin on mosquito susceptibility to the causative agent of malaria]. / Otsutstvie vozdeistviia piretroidov del'tametrina i tsipermetrina na vospriimchivost' komarov k vozbuditeliu maliarii.

Mosquitos Ae. aegypti and An. stephensi contact with sublethal doses of deltametrin and cypermetrin pyretroids at larval stage and in grown state, when diet includes sugar with pyretroids, had no influence on the sensitivity of survived females to malaria agents P. gallinaceum and P. berghei. Mosquitos under experiment showed no obvious inhibition of the physiological condition in comparison with the control ones.