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INTRODUCTION AND AIM: Hepatocellular carcinoma (HCC) is the third most frequent cancer of digestive tract tumors in Peru, with a high mortality rate of 17.7 per 100,000 inhabitants. A significant number of HCC cases in Peru do not follow the classic clinical epidemiology of the disease described in other parts of the world. Those patients present with a distinct transcriptome profile and a singular tumor process, suggesting a particular type of hepatocarcinogenesis in a portion of the Peruvian population. Our aim was to understand the clinical and biologic involvement of the epigenetic profile (methylation) and gene expression (transcriptome) of HCC in Peruvian patients. METHODS: HCC and liver transcriptome and DNA methylation profiles were evaluated in 74 Peruvian patients. RESULTS: When grouped by age, there was greater DNA methylation in younger patients with HCC but no differences with respect to the transcriptomic profile. A high prevalence of the hepatitis B virus (HBV) (>90%) was also observed in the younger patients with HCC. Enrichment analyses in both molecular profiles pinpointed PRC2 as an important molecular effector of that liver tumor process in Peruvian patients. CONCLUSION: HCC in Peruvian patients has a unique molecular profile, associated with the presence of HBV, as well as overall DNA hypermethylation related to undifferentiated liver cells or cellular reprogramming.
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Methylene blue (MB) is the oldest synthetic antimalarial. It is not used anymore as antimalarial but should be reconsidered. For this purpose we have measured its impact on both chloroquine sensitive and resistant Plasmodium strains. We showed that around 5 nM of MB were able to inhibit 50% of the parasite growth in vitro and that late rings and early trophozoites were the most sensitive stages; while early rings, late trophozoites and schizonts were less sensitive. Drug interaction study following fractional inhibitory concentrations (FIC) method showed antagonism with amodiaquine, atovaquone, doxycycline, pyrimethamine; additivity with artemether, chloroquine, mefloquine, primaquine and synergy with quinine. These results confirmed the interest of MB that could be integrated in a new low cost antimalarial combination therapy.
Assuntos
Antimaláricos/farmacologia , Malária Falciparum/tratamento farmacológico , Azul de Metileno/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Animais , Antimaláricos/uso terapêutico , Relação Dose-Resposta a Droga , Interações Medicamentosas , Resistência a Medicamentos , Quimioterapia Combinada , Humanos , Concentração Inibidora 50 , Azul de Metileno/uso terapêutico , Testes de Sensibilidade Parasitária , Resultado do TratamentoRESUMO
In French Guiana, Quassia amara L. (Simaroubaceae) leaf tea is a well-known widely used traditional antimalarial remedy. Impact of the vegetal sampling condition on in vivo and in vitro antimalarial activity was assessed. Traditional infusions were prepared with juvenile or mature leaves, both either fresh or dried. Results showed that growing stage and freshness of vegetal material exert a striking effect on antimalarial activity, both in vitro and in vivo. By far, leaf tea made from fresh juvenile (FJ) Quassia amara leaves was the most active. In vitro, active component (simalikalactone D) concentration correlates biological activities, although unexplained subtle variations were observed. In vivo, tea made with dried juvenile (DJ) leaves displays a peculiar behavior, meaning that some components may help simalikalactone D delivery or may be active in vivo only, therefore enhancing the expected curative effect of the traditional preparation.
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Antimaláricos/farmacologia , Bebidas , Dessecação , Malária/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Plasmodium yoelii , Quassia/crescimento & desenvolvimento , Animais , Antimaláricos/química , Antimaláricos/normas , Antimaláricos/uso terapêutico , Cromatografia Líquida de Alta Pressão , Guiana Francesa , Malária/parasitologia , Camundongos , Testes de Sensibilidade Parasitária , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/crescimento & desenvolvimento , Controle de Qualidade , Quassia/química , Quassinas/análiseRESUMO
French Guiana (North-East Amazonia) records high malaria incidence rates. The traditional antimalarial remedy most widespread there is a simple tea made out from Quassia amara L. leaves (Simaroubaceae). This herbal tea displays an excellent antimalarial activity both in vitro and in vivo. A known quassinoid, simalikalactone D (SkD), was identified as the active compound, with an IC(50) value of 10nM against FcB1 Plasmodium falciparum chloroquine resistant strain in vitro. Lastly, it inhibits 50% of Plasmodium yoelii yoelii rodent malaria parasite at 3.7 mg/kg/day in vivo by oral route. These findings confirm the traditional use of this herbal tea.
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Antimaláricos/farmacologia , Fitoterapia , Plasmodium falciparum/efeitos dos fármacos , Quassia/química , Quassinas/química , Quassinas/farmacologia , Animais , Antimaláricos/química , Bebidas , Guiana Francesa , Medicina Tradicional , Estrutura Molecular , Roedores/parasitologiaRESUMO
Chabirenia cayennensis n. g., n. sp. (Nematoda: Rhabdiasidae) is described from the teiid lizard Ameiva ameiva. A total of 139 worms were recovered, all females, from the mucous glands of the buccal cavity. The worm has a free-living phase in a homogonic life-cycle. Infective larvae are enclosed in a sheath with chequered ornamentation and composed of two exuviae. The new genus is distinct from the five known genera of the family, Pneumonema Johnston, 1916, Acanthorhabdias Pereira, 1927, Entomelas Travassos, 1930, Rhabdias Stiles and Hassall, 1905 and Neoentomelas Hasagawa, 1989, in the following characters: helical habitus, longitudinal cuticular crests, very tiny buccal cavity without thick walls and three oesophageal onchia. Several characters of this new rhabdiasid suggest the Strongylida.
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Lagartos/parasitologia , Mucosa Bucal/parasitologia , Rhabditoidea/classificação , Animais , Feminino , Rhabditoidea/anatomia & histologia , Rhabditoidea/crescimento & desenvolvimento , Rhabditoidea/isolamento & purificação , América do SulRESUMO
In order to evaluate the antimalarial potential of traditional remedies used in French Guiana, 35 remedies were prepared in their traditional form and screened for blood schizonticidal activity in vitro on Plasmodium falciparum chloroquine re4sistant strain (W2). Some of these extracts were screened in vivo against Plasmodium yoelii rodent malaria. Ferriprotoporphyrin inhibition test was also performed. Four remedies, widely used among the population as preventives, were able to inhibit more than 50% of the parasite growth in vivo at around 100 mg/kg: Irlbachia alata (Gentiananceae), Picrolemma pseudocoffea (Simaroubaceae), Quassia amara (Simaroubaceae), Tinospora crispa (Menispermaceae) and Zanthoxylum rhoifolium (Rutaceae). Five remedies displayed an IC50 in vitro < 10 microg/ml: Picrolemma pseudocoffea, Pseudoxandra cuspidata (Annonaceae) and Quassia amara leaves and stem, together with a multi-ingredient recipe. Two remedies were more active than a Cinchona preparation on the ferriprotoporphyrin inhibition test: Picrolemma pseudocoffea and Quassia amara. We also showed that a traditional preventive remedy, made from Geissospermum argenteum bark macerated in rum, was able to impair the intrahepatic cycle of the parasite. For the first time, traditional remedies from French Guiana have been directly tested on malarial pharmacological assays and some have been shown to be active.
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Antimaláricos/isolamento & purificação , Antimaláricos/uso terapêutico , Avaliação Pré-Clínica de Medicamentos/métodos , Administração Oral , Animais , Antimaláricos/classificação , Modelos Animais de Doenças , Etanol , Feminino , Guiana Francesa/etnologia , Humanos , Malária Falciparum/tratamento farmacológico , Camundongos , Fitoterapia , Componentes Aéreos da Planta/química , Raízes de Plantas/química , Plantas Medicinais/química , ÁguaRESUMO
Carrageenan oedema, a classical experimental model commonly used to test activity of anti-inflammatory drugs, was used to evaluate the therapeutic activity of a low-potency mineral complex (MC). The MC was administered in... (AU)