An aqueous extract of Khaya senegalensis (Desv.) A. Juss. (Meliaceae) prevents seizures and reduces anxiety in kainate-treated rats: modulation of GABA neurotransmission, oxidative stress, and neuronal loss in the hippocampus.

Ethnopharmacological relevance: Temporal lobe epilepsy is the most common form of drug-resistant epilepsy. Therefore, medicinal plants provide an alternative source for the discovery of new antiepileptic drugs. Aim of the study: This study was aimed at investigating the antiepileptic- and anxiolytic-like effects of an aqueous extract of Khaya senegalensis (K. senegalensis) in kainate-treated rats. Methods: Seventy-two rats received a single dose of kainate (12 mg/kg) intraperitoneally. Those that exhibited two hours of status epilepticus were selected and monitored for the first spontaneous seizure. Then, animals that developed seizures were divided into 6 groups of 8 rats each and treated twice daily for 14 days as follows: negative control group received per os (p.o.) distilled water (10 ml/kg); two positive control groups received either sodium valproate (300 mg/kg, p.o.) or phenobarbital (20 mg/kg, p.o.); and three test groups received different doses of the extract (50, 100, and 200 mg/kg, p.o.). In addition, a group of 8 normal rats (normal control group) received distilled water (10 ml/kg, p.o.). During the treatment period, the animals were video-monitored 12 h/day for behavioral seizures. At the end of the treatment period, animals were subjected to elevated plus-maze and open field tests. Thereafter, rats were euthanized for the analysis of γ-aminobutyric acid (GABA) concentration, oxidative stress status, and neuronal loss in the hippocampus. Results: The aqueous extract of K. senegalensis significantly reduced spontaneous recurrent seizures (generalized tonic-clonic seizures) and anxiety-like behavior compared to the negative control group. These effects were more marked than those of sodium valproate or phenobarbital. Furthermore, the extract significantly increased GABA concentration, alleviated oxidative stress, and mitigated neuronal loss in the dentate gyrus of the hippocampus. Conclusion: These findings suggest that the aqueous extract of K. senegalensis possesses antiepileptic- and anxiolytic-like effects. These effects were greater than those of sodium valproate or phenobarbital, standard antiepileptic drugs. Furthermore, these effects are accompanied by neuromodulatory and antioxidant activities that may be related to their behavioral effects. These data justify further studies to identify the bioactive molecules present in the extract for possible future therapeutic development and to unravel their mechanisms of action.

Sensitivity of Plasmodium falciparum to amodiaquine and chloroquine in central Africa: a comparative study in vivo and in vitro.

A comparative study in vivo of amodiaquine efficacy (35 mg/kg over 3 d) and chloroquine (25 mg/kg over 3 d) was conducted in 1991 and 1992 in Cameroon and Congo in 123 patients with uncomplicated Plasmodium falciparum malaria. Amodiaquine was more effective than chloroquine, with parasite clearance by day 7 in 79.7% of the patients compared with 59.4%. Sixteen of 32 (50%) P. falciparum isolates tested in vitro were resistant to chloroquine and only 3 of 34 (9%) were resistant to amodiaquine. 5.3% of patients treated with amodiaquine complained of pruritus and 18.7% of nausea, compared with 15.7% and 5% respectively of those treated with chloroquine.

[Sensitivity in vivo and in vitro of Plasmodium falciparum to chloroquine and amodiaquine in Bangangte (west Cameroon)]. / Sensibilité in vivo et in vitro de Plasmodium falciparum a la chloroquine et à l'amodiaquine à Bangangte (ouest-Cameroun).

A cross-sectional malaria survey was conducted during the rainy season in Bangangté (West-Cameroon), a town of 90,000 inhabitants located in the high tablelands zone of Cameroon. An in vivo study revealed that 50% of P. falciparum malaria patients were resistant to chloroquine (25 mg/kg over 3 days) and 26.3% to amodiaquine (35 mg/kg over 3 days) at a RII/RIII level. In addition, plasmodial indices indicated that malaria was mesoendemic in this area of Cameroon.

Mefloquine resistant malaria in Cameroon and correlation with resistance to quinine.

Based on the results of in vitro sensitivity of Plasmodium falciparum to chloroquine, quinine and mefloquine, and evaluation of drug consumption conducted in 1987-1988 in four areas in the north and south-west of Cameroon, two opposite situations were encountered in this country. In northern Cameroon where mefloquine resistance is prevalent a close correlation was found between the responses of P. falciparum to mefloquine and to quinine, but not between mefloquine and chloroquine. In the south, where chloroquine resistance is highly prevalent, no correlation was found neither between mefloquine and chloroquine nor mefloquine and quinine, but the responses to quinine and chloroquine appear partly correlated. These results lead to formulate the hypothesis of a "southern" type of P. falciparum submitted to a high chloroquine drug pressure inducing a secondary cross resistance, whilst a "northern" type submitted to a relatively high and abortive quinine drug pressure inducing a primary quinine resistance and a secondary cross resistance with mefloquine.

Multi-drug resistant falciparum malaria in Cameroon in 1987-1988. I. Stable figures of prevalence of chloroquine- and quinine-resistant isolates in the original foci.

The status of drug-resistant Plasmodium falciparum in Cameroon was determined in 1987-1988 in 221 children who were selected for chloroquine and quinine in vitro microtests. Resistance to quinine was found in 17% of 72 isolates from the southern part of the country, and in 7% of 87 isolates from the northern part of the country. The effective concentrations of 50% and 90% (EC50 and EC90) differed little from those observed in 1986. In southern Cameroon, 38 (51%) of 74 individuals harbored chloroquine-resistant isolates. The EC50 ranged from 8 to 553 nmol and the mean +/- SD EC50 was 154 +/- 148 nmol. In contrast, in the northern area, all but one of the 120 subjects studied had EC50 values below the cutoff limit of 80 nmol (mean = 20 nmol). In vivo 7-day assays performed with chloroquine at a dose of 25 mg/kg in 389 individuals from the southwestern part of the country clearly confirmed RII-RIII levels of resistance in 18-52% of the cases, depending on the location studied. In the northern area, in vivo 7-day assays at a chloroquine dose of 10 mg/kg showed 36 of 39 subjects studied to have drug-sensitive parasites. Based on these results, it appears that after a rapid emergence of resistance that occurred in southern Cameroon, the prevalence of chloroquine- and quinine-resistant parasites remained fairly stable from 1986 to 1988. The stable difference between the northern and southern areas is believed to be related to both the lower rate of transmission and lower chloroquine drug pressure in the north.

Multi-drug resistant falciparum malaria in Cameroon in 1987-1988. II. Mefloquine resistance confirmed in vivo and in vitro and its correlation with quinine resistance.

To further document the phenomenon of Plasmodium falciparum resistance to mefloquine formerly described in Cameroon, complementary in vivo and in vitro studies were conducted. Two hundred six P. falciparum isolates were studied in vitro using an isotopic microassay with mefloquine solutions prepared daily. Using the cutoff limit of 30 nmol, 26 (20%) of 133 isolates from the northern part of the country were defined as being resistant to mefloquine. In contrast, only one of 73 isolates collected in the southern part of the country was resistant. In vivo 7-day assays were performed in the northern area in 57 asymptomatic P. falciparum carriers (age range 1-10 years) who were given a single 25 mg/kg dose of mefloquine (Lariam). Among 46 cases in which followup was possible, P. falciparum asexual parasites were cleared within five days in 38 cases, by days 6 and 7 in two cases, and remained detectable up to day 7 in six cases. Thus, these latter patients have a RII-RIII level of resistance by in vivo criteria. No resistance was found in 40 additional patients studied similarly in the southern region. These observations were made before any mefloquine drug pressure was exerted in the country, but results of cross-resistance and drug consumption studies support the hypothesis that in the northern region, where a close correlation (r = 0.67) was found between the response to quinine and mefloquine, the more frequent use of quinine may have induced a primary quinine resistance and a secondary mefloquine resistance (without chloroquine resistance).(ABSTRACT TRUNCATED AT 250 WORDS)

Mefloquine resistant malaria in cameroon and correlation with resistance quinine

Based on the results of in vitro sensitivity of Plasmodium falciparum to chloroquine, quinine and mefloquine, and evaluation of drug consumption conducted in 1987-1988 in four areas in the noth and south-west of Cameron, two opposite situations were encountered in this country. In northern Cameron where mefloquine resistance is prevalent a close correlation was found between the responses of P. falciparum to mefloquine and to quinine, but not between mefloquine and chloroquine. In the south, where chloroquine resistance is highly prevalent, no correlation was found neither between mefloquine and chloroquine nor mefloquine and quinine, but the responses to quinine and chloroquine appear partly correlated. These lead to formulate the hypothesis of a "southern" type of P. falciparum submitted to a high chloroquine drug pressure inducing a secondary cross resistance, whilst a "northern"type submitted to a relatively high and abortive quinine drug pressure inducing a primary quinine resistance and a secondary cross resistance with mefloquine

Patterns of in vitro resistance to chloroquine, quinine, and mefloquine of Plasmodium falciparum in Cameroon, 1985-1986.

The drug sensitivity of 246 Plasmodium falciparum isolates was studied in vitro in five areas of Cameroon at the end of 1985. Results demonstrate that parasites resistant either to chloroquine, quinine, or mefloquine, or to two of these drugs, were prevalent in four of the areas investigated, but the drug response pattern varies widely from one area to another. The recent explosive emergence of chloroquine resistance in the south of the country, where both prevalences and levels are very high (up to 86%), contrasts with only moderate levels of resistance in the north. This may be related to differences in transmission by mosquitoes between Sahel and forest areas. Quinine resistance was observed in 24% of the isolates studied in vitro and was frequently associated with chloroquine resistance. The presence of isolates responding poorly to mefloquine, observed mainly in northern Cameroon, suggests that resistance may occur in areas where the drug has never been used.

[New focus of chloroquine-resistant malaria in a forestry zone in Cameroon]. / Nouveau foyer de paludisme chloroquino-résistant en zone forestière au Cameroun.

In vitro sensitivity of P. falciparum to chloroquine and quinine was studied in Hevecam rubber plantations of la Nyete in Cameroon, located at 45 km in the south east of Kribi in a forest area. More than half of the isolates studied (14/25) were resistant to chloroquine (EC50 greater than 80 nmole/l). The mean EC50 and EC99 were 113 nmole/l and 4,110 nmole/l respectively. The sensitivity to quinine was decreased, as compared to other area of the country. Kribi is the third area of chloroquine-resistance known in Cameroon.

[Epidemiologic and radiologic study of urinary bilharziosis in a focus at the Barombi Lakes (Mémé Department), Cameroon]. / Etude épidémiologique et radiologique de la bilharziose urinaire dans le foyer des lacs Barombi (Département de la Mémé) Cameroun.

A recent epidemiological and radiological study of urinary schistosomiasis in the Barombi lake foci (South West Cameroon) shows that the intensity of the disease is very high, 76% and 50% in Barombi Kotto and Barombi Mbo respectively, when compared to the level observed by DUKE and MOORE during a five year control period, from 1970 to 1975, respectively 6.9% and 2.4% in Barombi Kotto and Barombi Mbo. The endemicity is not influenced by age or sex. On the average, the parasitic load is highest in the 5-15 years age group. Bulinus camerunensis and B. rohlfsi are the known intermediary hosts of this parasite, with an infection rate of 17.2%. B. camerunensis is the most abundant species, but B. rohlfsi is the frequently infected. The bilharzia patient had very important and very frequent lesions of the urinary system. A normal X-ray shows calcifications localised on the ureter and more often on the bladder. The frequency of these calcifications increases with age. The intravenous pyelography (IVP) shows functional (delay in secretion observed in 47% of cases) and morphological lesions (87% of the patients). Morphologically, the bladder present irregularities of the contours and the mucosa. Irregular contours of the ureters with strictures, including dilation and stenosis, are observed. On the kidney, dilated calyces (hydronephrosis due to obstruction on lower side) are evident. There does not seem to be any relation between the number of eggs discharged by the patient and the importance or frequency of lesions observed in a normal X-ray or IVP.

High level of sensitivity to chloroquine of 72 Plasmodium falciparum isolates from southern Cameroon in January 1985.

The sensitivity to chloroquine, quinine and mefloquine of Plasmodium falciparum isolates from 3 areas of southwest Cameroon was evaluated using an in vitro microtest with estimation of parasite growth by 3H-hypoxanthine incorporation. Among 2,429 children examined, P. falciparum was found on thin smears in 124 of them, 76 isolates were submitted to in vitro tests and 72 were successful. In the locations studied, some of which are close to the area of Limbe where in vivo resistance has been reported, all 72 isolates were found fully sensitive to low concentrations of chloroquine (mean EC50 5.9 ng/ml or 18.5 nmol/l of medium). In 47 of these isolates simultaneously tested using WHO microtest predosed plates, the sensitivity was identical. Out of 39 tests performed with quinine, 35 were successful. While most strains responded to low concentrations, some showed a decreased sensitivity to the drug, the EC50 of 4 of them being in the range 230-300 nmol/l. Each of the 17 isolates tested with mefloquine was susceptible to very low concentrations of freshly prepared drug solution. While chloroquine-resistant strains may already exist in Cameroon, the present study suggests that they would be restricted to a limited area and are not widespread. Data also suggest that monitoring of the sensitivity of P. falciparum to quinine might soon be necessary.

Effects of a new antitumor compound, mopidamol, on thymidine and 2-deoxyglucose transport in leukaemic L 1210 cells.

The effects of 2,2',2",2"'-[(4-piperidinopyrimido[5,4-d]pyrimidine-2,6- diyl)dinitrilo]-tetraethanol (mopidamol, RA-233), a drug with antitumour properties, have been studied on membrane transports of L 1210 cells grown in culture. The results show that mopidamol is an inhibitor of thymidine and 2-deoxyglucose transport at concentrations less than or equal to 10(-4) mol/l. The inhibitory effect on cancer cells occurs as soon as 20 s after contact with the drug. Lineweaver and Burk's plots demonstrate a non-competitive type inhibitory effect on membrane transports. In addition, thymidine incorporation in DNA is decreased in the presence of mopidamol.

[Effect of methotrexate on oxygen consumption of L1210 cells and their isolated mitochondria]. / Effets du méthotrexate sur la consommation d'oxygène des cellules L1210 et de leurs mitochondries isolées.

Methotrexate, at doses inhibiting cell growth without any lethal effect, alters oxygen consumption in L 1210 cells as soon as 3 hrs. after culture. After a 24 hrs. treatment with methotrexate, there is a close relationship between cellular oxygen uptake and growth inhibition. These two effects are reversible. With mitochondria from treated cells, an inhibition of respiration is observed in the presence of glutamate-malate. No effect occurs with succinate. These results in vitro are compatible with concentrations used in patients.