Antimalarial efficacy, cytotoxicity, and genotoxicity of methanolic stem bark extract from Hintonia latiflora in a Plasmodium yoelii yoelii lethal murine malaria model.

Traditional medicines have been used to treat malaria for thousands of years and are the source of artemisinin and quinine derivatives. With the increasing levels of drug resistance, the high cost of artemisisnin-based combination therapies, and fake antimalarials drugs, traditional medicine have become an important and sustainable source of malaria treatment. For the benefit of those who use traditional medicine to treat malaria, there is an urgent need to study the efficacy and toxicity of herbal remedies. Hintonia latiflora stem bark infusions are use in Mexican traditional medicine to treat malaria, diabetes, and gastrointestinal diseases. Its efficacy in the treatment of complicated malaria and its ability to generate DNA damage to the host is not fully evaluated. In our search for antimalarial natural products, in the present study, we tested the efficacy of H. latiflora stem bark methanolic extract (HlMeOHe) in CD1 male mice infected with lethal Plasmodium yoelii yoelii and its in vivo cytotoxicity and genotoxicity. To assess the antimalarial activity, the extract was evaluated in a 4-day test scheme in oral doses of 1,200, 600, and 300 mg/kg prior acute toxicity test; oral chloroquine (15 mg/kg) was used as positive control. The ability of 1,200 mg/kg of HlMeOHe to induce cytotoxicity and DNA damage in the peripheral blood of mice was assessed using a fluorochrome-mediated viability test and the micronucleus (MN) assay; N-ethyl-N-nitrosourea (ENU) was used as a positive control. HlMeOHe median acute toxicity (LD50) was 2,783.71 mg/kg and LD10 was 1,293.76 mg/kg (taken as the highest work dose). Plasmodium yoelii yoelii-infected mice in the untreated control group died between 6 and 7 days post-infection (PI) with parasitemia over 70%. Even though mice treated with 600 and 300 mg/kg showed a chemosuppression percentage of total parasitemia of 99.23 and 23.66, respectively, animals in both groups died 6 to 7 days PI with parasitemia over 45%. A 4-day dosage of 1,200 mg/kg of the extract showed, in the P. yoelii yoelii-infected mice, a 100% chemosuppression of total parasitemia on 5 days PI and a 23 days survival time with a mean parasitemia of 23.6% at the date of death. Only mice treated with chloroquine survived until the end of the experiment. Cell viability was not affected. The average number of micronuclei in the treated mice increased significantly (P < 0.05) to 4.8 MN when compared with the untreated control group (0.9 MN). The results obtained in this study showed that the infection outcome of P. yoelii yoelii-infected mice is affected by HlMeOHe. Although a concentration of 1,200 mg/kg of HlMeOHe is suitable to use in the treatment of malaria fever, slowed down the parasite replication, retarded the patency time, and increased the infected P. yoelii yoelii mice survival time, its chemical composition should be studied in detail in order to reduce its genotoxic potential.

Biological assay of a novel quinoxalinone with antimalarial efficacy on Plasmodium yoelii yoelii.

Compound 1-methyl-7-nitro-4-(5-(piperidin-1-yl)pentyl)-3,4-dihydroquinoxalin-2(1H)-one (VAM2-6) was evaluated against a blood-induced infection with chloroquine-sensitive Plasmodium yoelii yoelii lethal strain in CD1 mice in a 4-day test scheme. LD50 of the compound was 56.51 mg/kg and LD10 was 20.58 mg/kg (taken as the highest dose). Animals were treated by oral gavage of 20, 10, and 5 mg/kg. Mice in the untreated control group showed a progressively increasing parasitemia leading to mouse death on 6 days post-infection; in this group, all mice showed parasites in the blood on the fifth day of sampling; the mean parasitemia on that day was 19.4%. A 4-day dosage of 20 mg/kg of VAM2-6 showed a 97% chemosuppression of total parasitemia on the fifth day, a 28 days survival time, and 20% of cured animals. A 4-day dosage of 10 and 5 mg/kg showed 85 and 37%, respectively, chemosuppression of total parasitemia on the fifth day; but all mice died from days 6 to 9 post-infection with increasing parasitemia. Mice treated with chloroquine at 5 mg/kg survived during the experiment. The results obtained in this study showed that the infection outcome of P. yoelii yoelii-infected mice is affected by VAM2-6 compound by slowing down the parasite replication, retarding the patency time, and increasing their survival time. Although compound VAM2-6 was active at higher doses than chloroquine, these results leaves a door open to the study of its structure in order to improve its antimalarial activity.

In vivo genotoxicity and cytotoxicity assessment of a novel quinoxalinone with trichomonacide activity.

The compound VAM2-6 (1-methyl-7-nitro-4-(5-(piperidin-1-yl)pentyl)-3,4-dihydroquinoxalin-2(1H)-one) has previously been shown to have an in vitro efficacy of 100% at a concentration of 100 µg ml(-1) against Trichomonas vaginalis, a protozoon parasite that causes the sexually transmitted disease trichomoniasis. Because VAM2-6 is a quinoxaline derivative and given the lack of studies on the genotoxic activity of this compound, the present study was undertaken to evaluate its ability to induce DNA damage in the peripheral blood of mice using single-cell gel electrophoresis (SCGE or comet assay) and the micronucleus (MN) assay. Cell viability was assessed using a fluorochrome-mediated viability test. The compound was tested on CD1 mice at 60, 40 and 10 mg kg(-1) body weight administrated intraperitoneal (i.p.) in a single dose. Peripheral blood samples were collected 24 and 48 h after treatment. N-Ethyl-N-nitrosourea (ENU) was used as a positive control for the comet and micronucleus assays. The results showed that i.p. VAM2-6 induced single-strand DNA breaks and increased the average number of micronuclei in the treated mice in a dose-dependent manner at 60, 40 and 10 mg kg(-1). Cell viability decreased at 24 h but recovered at 48 h for all three evaluated doses. Therefore, the chemical structure of VAM2-6 should be modified to reduce its genotoxic potential.

Blackwater fever like in murine malaria.

Blackwater fever (BWF) is the term used to designate the occurrence of hemoglobin pigments in the urine of patients infected with malaria parasites. BWF is more often associated with Plasmodium falciparum infection in man. The pathogenesis of BWF has not been explained satisfactorily. In the present study, the clinical and pathological observations made upon CD1 mice infected with Plasmodium yoelii yoelii lethal strain with clinical signs of hemoglobinuria and acute renal failure were evaluated. From the 40 P. yoelii yoelii-infected mice, 14 presented hemoglobinuria. In the observations, it was emphasized that hemoglobinuria occurred in the animals 1-2 days before they die. At 6 days post-infection, infected hemoglobinuric mice (HM) exhibited clinical signs such as dark red urine, apnea, and evident oliguria and hematuria; urine microscopical examination showed very few red blood cells. The entire non hemoglobinuric infected mice had a high parasitemia preceding the time of death, while the HM parasitemia was just detectable. In HM, marked hepatosplenomegaly, anemia, and renal and hepatic dysfunction were observed with the blood chemistry analysis at 6 days post-infection. Severe renal lesions were demonstrated in histopathological and scanning electron microscopy samples. Occlusion and necrosis of convoluted tubules were the main lesions found. The conditions required for the experimental production of hemoglobinuria in CD1 mouse infected by P. yoelii yoelii is still unknown. The clinical picture of a BWF, like in our rodents, was produced exclusively by the interaction between the parasite and its host. Results showed that hemoglobinuria in CD1 mice infected with P. yoelii yoelii and BWF in man infected with P. falciparum are similar in their pathogenesis.

Etiopathogenesis of Burkitt's lymphoma: a lesson from a BL-like in CD1 mouse immune to Plasmodium yoelii yoelii.

INTRODUCTION: There is a jaw cancer that develops in children five to eight years old in holoendemic malaria regions of Africa, associated to malaria and Epstein Barr virus infections (EBV). This malignancy is known as endemic Burkitt's lymphoma, and histopatologically is characterized by a starry sky appearance. To date, no histopathologic expression of Burkitt's lymphoma has been reported in non-genetically manipulated experimental animals. The purpose of the study is to describe the case of a mouse immune to Plasmodium yoelii yoelii (Pyy) that developed a Burkitt's lymphoma-like neoplasm after repeated malaria infections. RESULTS: Immune mouse 10 (IM-10) developed neoplasms at eight months of age, after receiving three Pyy inoculations. At autopsy eight subcutaneous tumors were found of which the right iliac fosse tumor perforated the abdominal wall and invaded the colon. The histopathologic study showed that all neoplasms were malignant lymphomas of large non-cleaved cells also compatible with variants or previous states of development of a Burkitt's lymphoma-like. The thymus, however, showed a typical starry sky Burkitt's lymphoma-like neoplasm. CONCLUSIONS: Neoplasm development in CD1 mouse is associated to both, immunity against malaria and continuous antigenic stimulation with living parasites.It is the first observation of a histopathologically expressed Human Burkitt's lymphoma-like neoplasm in a non-genetically manipulated mouse.Chronic immune response associated to neoplasms development could probably be not an exclusive expression of malaria-host interaction but, it could be a pattern that can bee applied also to other agent-host interactions such as host-bacteria, fungus, virus and other parasites.

Cryptosporidiosis and other intestinal protozoan infections in children less than one year of age in Mexico City.

Parasitic diseases are very important in Mexico because of their economic impact and adverse effects on normal growth in children. Cryptosporidiosis has been associated with acute diarrhea in immune competent and incompetent human hosts, fecal contamination of drinking water sources, and handling of animals. Due to the lack of reports on cryptosporidiosis in Mexico, we conducted a parasitologic study in children with diarrhea and other clinical symptoms. The main objectives were 1) to determine the prevalence of cryptosporidiosis in children less than one year of age in Mexico City, and 2) to correlate Cryptosporidium infection with gastrointestinal symptoms. Two hundred fecal samples from children seen at the Gabriel Mancera Familiar Medicine Unit of the Instituto Mexicano del Seguro Social were studied. Children were divided into two groups. Group A was composed of sick children with 6-8 watery diarrheic episodes every 24 hours attended at the emergency service. Group B was composed of healthy babies getting routine check ups. Only children in group A were found to be infected with intestinal protozoa (50% with Giardia lamblia, 41% with Cryptosporidium spp., and 4% with Entamoeba histolytica). The results suggested a high incidence of Cyrptosporidium infections in children in Mexico City, which make these observations useful for future studies.

[Origin of malarial paroxysm]. / El origen del paroxismo malárico.

This study attempts the reconstruction of the most characteristic clinical picture of the acute phase of malaria, the malarial paroxysm, describing the elements that participate on the part of the parasite and the host, the way they become integrated, and how they function to produce the classical clinical manifestations of what we call malaria.

On the current existence of a coccidial line of development in the malaria parasites: a theory

Most opinion favors the origin of the malaria parasites from a coccidial ancestor. It is assumed that whatever the process through which the coccidia differentiated into a Plasmodium this phenomenon very probably occured millions of year ago, and during that differentiation process the original coccidia vanished. Therefore it has never repeated. At the light of some experiments the existence, at the present time, of a coccidial cycle of development in the malaria parasites, is proposed. The conection routes and mechanisms through which the malaria parasite changes to a coccidial life, and the routes in reverse are exposed. Transmission of the malaria-coccidial forms is suggested

Cisticercosis humana y porcina. Su conocimiento e investigación en México / Human and porcine cysticercosis. Its knowledge and research in Mexico

Contribuciones realizadas por expertos en torno a la cisticercosis durante el Encuentro Nacional sobre Cisticercosis, donde los participantes fueron divididos en seis grupos, de acuerdo con el campo de mayor dominio individual, en torno a la cisticercosis humana y porcina. La presente publicación contiene las conclusiones a las que llegó cada mesa de trabajo. El documento contiene los siguientes capítulos: I. Biología e inmunología II. Clasificación clínica III. Patología IV. Inmunodiagnóstico V. Tratamiento V. Epidemiología.