[Phenotypic variability in P. vivax with short- and long-term incubation period]. / Fenotipicheskaia izmenchivost' P. vivax s korotkoi i dlitel'noi inkubatsiiei.

The combined transmission of P. vivax phenotypes was studied. The phenotypes were determined by the duration of a latent parasitic development stage by comparing the intervals from first manifestations of malaria with short- and long-term incubations to its relapse. The study used data on 2493 patients treated with chloroquine (900 mg base for adults) alone at follow-ups in the North-Eastern Delhi (India) in 1988-1992. The combined transmission of P. vivax phenotypes was shown to differ in malaria with short- and long-term incubation. The P. vivax phenotype with manifestations on an average a year following infection in patients with mainly short-term incubation malaria and that with manifestations on an average year and a half after infection in a group of patients with primary long-term incubation malaria were significantly more frequently. Long-term incubation malaria shows simultaneously a larger number of phenotypes than does short-term incubation one. Patients with long-term incubation malaria display a combination of 2 phenotypes (6%) significantly less frequently than that of 3 different phenotypes or more (17%). The similar combinations were observed in the equal number of patients with short-term incubation malaria (7%).

Studies on the Plasmodium vivax relapse pattern in Delhi, India.

A five-year epidemiologic study of patients attending a malaria clinic in Delhi was conducted to find the relapse rate of infections with Plasmodium vivax, its seasonal correlation between the primary infection and subsequent relapses, the duration of the incubation period, and the patterns of relapse. By our definition, the relapse rate ranged from 23% to 44% depending on the duration of follow-up. The relapse pattern observed in the study clearly suggests the existence of both tropical and temperate zone types of P. vivax in the population characterized by distinct incubation periods and the possible existence of P. vivax subpopulations characterized by primary long incubation periods. The implication of different incubating forms of P. vivax on the epidemiology and control of malaria is also discussed.

[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.

[An evaluation of the spectrum of Plasmodium vivax subpopulations by the results of an experimental study of late relapses in Delhi]. / Otsenka spektra subpopuliatsii Plasmodium vivax po rezul'tatam éksperimental'nogo izucheniia otdalennykh retsidivov v Deli.

The spectrum of Plasmodium vivax subpopulations could be evaluated by analyzing the results of experimental studies of late relapses in P. vivax malaria in north-western Delhi. The spectra of the subpopulations causing late recurrences were different for malaria with short-and longterm incubations. The conclusions previously made by mathematical stimulation as to that malaria with longterm incubation is mainly transmitted at the beginning of the season have been confirmed. Based on the results of the frequency analysis, 6 P. vivax subpopulations with the values of their development duration of 15, 240, 300, 390, 720, and 1020 days, respectively, were identified for formalization of an epidemic process.

[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 mathematical modelling of tropical malaria]. / Matematicheskoe modelirovanie tropicheskoi maliarii.

The new mathematical model of P. falciparum malaria has been created. One means the operational forecast of epidemic process when different control measures are realized. The original modelling methodology for epidemics is used. The proposed methodology is allowed to take into account the natural variety of model's parameters. The malaria model consists of the nonlinear integro-differential in partial derivatives combined equations including individual and population characteristics. The informatics technologies permits to see information about model and its grounds. The model's verification has been done on data of Garki-project.

Malaria paradigms in India and control strategies.

The paper gives a brief history of malaria control in India through the National Malaria Control Programme (NMCP), National Malaria Eradication Programme (NMEP), implementation of the Modified Plan of Operation (MPO), strengthening of malaria control by launching P. falciparum Containment Programme (PfCP) and the Urban Malaria Scheme (UMS). Making reference to various evaluations of the NMEP, the paper analyses the present malaria situation and brings out reasons demanding change in the strategy of malaria control in consonance with the global malaria control strategy of the World Health Organization (WHO). The epidemiological analysis has revealed that the present adverse malaria situation concentrates mostly under the following five epidemiological paradigms viz. (i) tribal malaria, (ii) rural malaria, (iii) urban malaria, (iv) industrial malaria, and (v) border malaria. Malaria control requires specific approaches and control strategies for each paradigm. We have suggested changes/augmentation in the organizational set-up beginning from NMEP Directorate to the most peripheral health units. The primary responsibility of malaria prevention and control including cost in developmental projects should be shared by the corporate sectors through intersectoral coordination. Residual problems during maintenance phase of the project would come under the general health services. International and bilateral cooperation increases resources availability. The available tools and their rational use for malaria control in different epidemiological paradigms has been discussed with emphasis on integrated control, selective use of chemical insecticides and adoption of cost-effective and sustainable malaria control methods. In this context, intersectoral collaboration, community participation, training, operational research and health education have been discussed as the vital components for effective malaria control.

[A method for stratifying malariogenic territories in order to construct a system of mathematical models of the prevalence of malaria. 1]. / Metodika stratifikatsii maliariogennykh territorii s tsel'iu postroeniia sistemy matematicheskikh modelei rasprostraneniia maliarii. Soobshchenie 1.

The paper describes procedures for stratifying malariogenic areas that are homogeneous in the development pattern for epidemic stratum rises, which will be used to design a set of mathematical malaria spread models. The first stage of the procedures is to stratify P. falciparum and P. vivax malaria on phase planes. The morbidity rate of P. falciparum and P. vivax malaria was analyzed in the north-western areas of India in 1975-1990. Eighty-two observations provided 4 types of phase curves for tropic malaria, which form a polygon, a loop polygon, U-shaped ones and those without any specific signs and 4 groups of phase curves for P. vivax malaria and the U-shaped phase curve with a loop for P. vivax malaria. It is shown that there is a steady-state pattern of phase curve changes in 71%. It is suggested that the pattern of a phase curve can be a diagnostic characterization of the given area.

Importation of malaria into the USSR from Afghanistan, 1981-89.

Between 1981 and 1989, a total of 7683 cases of Plasmodium vivax [corrected] malaria were imported into the USSR from Afghanistan, mainly by demobilized military personnel. For 23.8% of these cases the clinical manifestations appeared within a month of returning to the USSR, for 22.5% after 1-3 months, for 20% after 4-6 months, for 2% after > 1 year, and for 0.6% after > 2 years. For 13 patients the clinical manifestations of malaria appeared 3 years after returning from Afghanistan (up to 38 months). Nearly 69% of the patients did not take malaria prophylaxis at all while they were in Afghanistan, and 19% took chloroquine irregularly. Only 12.5% of the patients received a full course of prophylactic treatment with primaquine before leaving Afghanistan. A total of 56% of the cases were detected during the period most favourable for malaria transmission in the USSR (May-September) and of these, half were imported into formerly malarious areas of the country. Activation of a surveillance system greatly reduced the consequences of the massive importation of malaria, to which the local vectors were susceptible.

[A new approach to overcoming the drug resistance of the causative agents of malaria]. / Novyi podkhod k preodoleniiu lekarstvennoi ustoichivosti vozbuditelei maliarii.

Progressively expanding area of multiresistant falciparum malaria and the profile of its resistance to drugs successively implemented into practice necessitate the elaboration of approaches to the "revival" of the drugs used. As with neoplastic cells, a correlation between plasmodium multiresistance with increased "outflow" of specific drugs from the cell is suggested, which is blocked by inhibition of Ca2+ transport. Reversion of resistance to chloroquine by a combination with Ca2+ channel blockers verapamil, tricyclic antidepressants (desipramine, protritreline, etc.), tricyclic antihistamine drugs (cyproheptadine), and reversion of resistance to sulfadoxine in combination with the antihistamine drug ketodiphene have been shown in vivo and in vitro. The function of Ca2+ channels is directly related to Ca2(+)-, Mg2(+)-dependent ATPase. Ph-metric techniques elaborated in the USSR make it possible to evaluate its activity, determine the inhibitors, differentiate them according to the effect. The authors have established reversion of P. berghei resistance to chloroquine, with the tricyclic antidepressants azaphen, aminazin, triftazin correlating with the degree of Ca2+, Mg2(+)-ATPase inhibition and to praziquantel, whose effect might be associated with the increased permeability of the cellular membrane to Ca2+. The inhibitors of Ca2+ transport have various parasitocidal activities which might be accounted for by the deficiency of this cation necessary for plasmodium development. The task is to elaborate safe optimum antimalarial drug/modulator of Ca2+ transport combinations. Multiresistance (genetically predetermined multifactorial cellular changes) may be associated with enhanced synthesis of transmembrane glycoprotein with varying molecular mass depending on the direction of resistance.

[A possible physico-chemical mechanism of cell fusion in skeletal muscle myogenesis by means of intercellular pinocytosis]. / Vozmozhnyi fiziko-khimicheskii mekhanizm sliianiia kletok v miogeneze skeletnoi myshtsy postredstvom mezhkletochnogo pinotsitoza.

The fusion mechanism of cells in myogenesis of skeletal muscle is proposed on the basis of capacity of forming intercellular contacts with pentalamellar structure to invaginate up to the formation of free vesicles, i.e. the intercellular pinocytosis. This process leads to a "loss" of the membrane material with the following perforation and rupture of the membrane at the site of cell contact. The formation of invaginations is connected with the clusterization of proteins on the cytoplasmic surface of plasmalemma, accompanied by an alteration of Gibbs' surface energy with the appearance of chemically induced and bending moments. The transition from the invagination to the vesicle depending on osmotic gradient of pressure between the fusing cells was estimated quantitatively. This gradient is determined by the mechanism of polymerization of protein subunits during the assembly of contractile elements in one of fusing cells.

[Clinical characteristics and diagnosis of stenocardia in persons with normal coronary vessels]. / Klinicheskie osobennosti i diagnostika stenokardii u lits s normal'nymi koronarnymi sosudami.

To date, the clinical pattern and electrocardiographic diagnosis of only one variant of coronary heart disease (CHD) with unchanged coronarogram, Prinzmetal's angina, have been worked out, while the diagnosis of other variants remains undeveloped. Clinical symptoms and possibilities of CHD diagnosis in the presence of intact coronary arteries have been evaluated in 67 coronary patients, the coronarograms being normal in 46 of those. The diagnosis of CHD was verified by means of various instrumental methods, including electrocardiographic tests and myocardial metabolic studies in conditions of frequent atrial stimulations. The results were computerized, using a specifically designed programme. Sets of signs identifying coronary patients with intact coronary arteries at questioning and noninvasive investigation are presented.

[Use of a universal formalized questionnaire in the differential diagnosis of cardiac and noncardiac pain]. / Ispol'zovanie universal'noi formalizovannoi ankety v differentsial'noi diagnostike koronarogennykh i nekoronarogennykh bolei.

A standard questionnaire, capable of describing chest pain sensations, has been offered for patients with coronary disease and neurocirculatory dystonia, and its diagnostic value is assessed. The questionnaire comprises five sections, each corresponding to a certain type of pain. A diagnostic statement is made after each section. The questionnaire can be analysed by a physician on the basis of individual clinical experience, or computer-processed. It possesses high sensitivity and specificity in detecting typical and atypical angina and cardialgia of different types. The questionnaire can identify a category of patients with chest pains, who require instrumental diagnostic investigation to specify their origin.

[The theory of pinocytosis. Factors determining the dynamics of pinocytosis in capillary endothelium]. / K teorii pinotsitoza. Faktory, opredeliaiushchie dinamiku pinotsitoza v éndotelii kapilliarov.

Peculiarities of the mechanism and conditions of pinocytosis vesicules formation in capillary endothelium are considered in relation to: 1) the size of a protein cluster which is formed from plasma proteins on the endotheliocyte plasma membrane surface, and initiates a caveole formation; 2) the value of intracapillary hydrostatic pressure providing energetics of the caveole transition in the vesicula and its comming off. The bound parameters of vesicules formation are calculated in comparison with the well-known experimental data. It is suggested that in other types of endocytosis the initial phase of the process (caveoles formation) is also connected with absorption of the protein molecules on the plasma membrane and their clusterisation. A possible explanation is given to the fact of vesicles quantitative increase in endothelium in hypertension.

[Vesicular transport in heart muscle tissue]. / Vezikuliarnyi transport v tkani serdechnoi myshtsy.

Myocardial vesicular transport has been examined, using intravital perfusion fixation staining with glutaraldehyde and ruthenium red. De novo capillary endothelial and plasmatic membrane formation of microvesicles has been demonstrated, and vesicular transport has been followed through its various stages. Myocardial vesicular transport is purposeful movement from capillary lumen through the endothelium (endocytosis-exocytosis) to intercellular space and therefrom to cardiomyocytes by means of endocytosis. Approximate scale of vesicular transcapillary transport is estimated at 7 mg protein per minute per 100 g wet myocardial tissue, and presupposes a fairly high cardiomyocyte endocytosis level.