Ecologic aspects of American tegumentary leishmaniasis. 5. Stratification of the spatial and seasonal activities of Phlebotominae (Diptera, Psychodidae) in areas of agricultural culture of the Vale do Ribeira region, State of S?o Paulo, Brazil

This paper deals with the investigation on the composition and stratification of the Phebotominae activity developed in patch and clear areas of high agricultural activity. The employment of a CDC light trap proved to be a useful tool in determining the local faune. Thirteen species of sandflies and a total of 5,423 individuals were caught. The catch places situated in the ecotone were the ones in which the results reached their best, being outstanding for Psychodopygus intermedius, Lutzomyia migonei and L. fischeri. Thereby, data lead us to believe they have acrodendrophilous habit. On the other hand, when the global results were gathered according to male and female categories, the first one proved to be predominant. In the analysis of seasonal distribution for the three species cited, it was clear that the high-activity peaks were bi- and tri-modal for different seasons. P. intermedius was almost the exclusive sandfly caught at ground level in the Autumn season. This exclusiveness has practically extended itself to the catch places situated in open field.     

Potential toxicity of flavonoids and other dietary phenolics: significance for their chemopreventive and anticancer properties

Flavonoids, including isoflavones, are natural components in our diet and, with the burgeoning interest in alternative medicine, are increasingly being ingested by the general population. Plant phenolics, which form moieties on flavonoid rings, such as gallic acid, are also widely consumed. Several beneficial properties have been attributed to these dietary compounds, including antioxidant, anti-inflammatory, and anticarcinogenic effects. Flavonoid preparations are marketed as herbal medicines or dietary supplements for a variety of alleged nontoxic therapeutic effects. However, they have yet to pass controlled clinical trials for efficacy, and their potential for toxicity is an understudied field of research. This review summarizes the current knowledge regarding potential dietary flavonoid/phenolic-induced toxicity concerns, including their pro-oxidant activity, mitochondrial toxicity (potential apoptosis-inducing properties), and interactions with drug-metabolizing enzymes. Their chemopreventive activity in animal in vivo experiments may result from their ability to inhibit phase I and induce phase II carcinogen metabolizing enzymes that initiate carcinogenesis. They also inhibit the promotion stage of carcinogenesis by inhibiting oxygen radical-forming enzymes or enzymes that contribute to DNA synthesis or act as ATP mimics and inhibit protein kinases that contribute to proliferative signal transduction. Finally, they may prevent tumor development by inducing tumor cell apoptosis by inhibiting DNA topoisomerase II and p53 downregulation or by causing mitochondrial toxicity, which initiates mitochondrial apoptosis. While most flavonoids/phenolics are considered safe, flavonoid/phenolic therapy or chemopreventive use needs to be assessed as there have been reports of toxic flavonoid-drug interactions, liver failure, contact dermatitis, hemolytic anemia, and estrogenic-related concerns such as male reproductive health and breast cancer associated with dietary flavonoid/phenolic consumption or exposures.     

Biology of the first generation of a laboratory colony of Nyssomyia intermedia (Lutz & Neiva, 1912) and Nyssomyia neivai (Pinto, 1926) (Diptera: Psychodidae)

The phlebotomine sand flies Nyssomyia intermedia (Lutz & Neiva, 1912) and Nyssomyia neivai (Pinto, 1926) are very close and may be involved in the transmission of Leishmania spp. Ross, 1903 in Brazil. The biology of the first laboratory-reared generations of these species, descended from insects captured in Além Paraíba (N. intermedia) and Corinto (N. neivai) in the Brazilian state of Minas Gerais, is described here. The captured females were fed on hamsters and maintained individually in rearing pots. Laboratory temperature and relative humidity were maintained at 25-26 masculineC and 80% respectively. The productivity of the first generation of N. intermedia was greater than that of N. neivai, and its development time clearly shorter, particularly for the second and third larval instars.     

Evaluation of a new plate hybridization assay for the laboratory diagnosis of imported malaria in Italy

A new molecular diagnostic method "Malaria-IBRIDOGEN" (Amplimedical S.p.A.--Bioline Division, Turin, Italy) based on a plate-hybridization assay for the simultaneous detection and identification of human malaria parasites was evaluated in this study. A target DNA sequence of the plasmodial 18S ribosomal RNA gene was amplified by polymerase chain reaction (PCR) and hybridized in microtiter wells with five biotinylated probes each specific for Plasmodium falciparum, P. vivax, P. malariae, P. ovale and the beta-globine human gene, respectively. Compared to the nested-PCR actually used in our laboratory for the molecular diagnosis of malaria, "Malaria-IBRIDOGEN" revealed an overall sensitivity of 100% (51/51) for the four human Plasmodium species testing 100 whole blood samples from people with malaria-like symptoms and fever. Specificity was 92% (45/49) considering four discordant samples as "false positive" by "Malaria-IBRIDOGEN". The assay showed a threshold of parasite density (detection limit) of 0.07 P. falciparum parasites/microliter, 0.15-1.5 P. vivax parasites/microliter, 0.3 P. malariae parasites/microliter and 0.4 P. ovale parasites/microliter of whole blood, respectively. This assay could be successfully applied to the laboratory diagnosis of malaria as a useful aid to microscopy.     

Description of Pintomyia limafalcaoae and Pintomyia antioquiensis,two new species of phlebotomine sand fly (Diptera,Psychodidae) from the Colombian Andes

Two new species of phlebotomine sand fly from Colombian Andes are described, belonging to the subgenus Pifanomyia of the genus Pintomyia. P. (P.) limafalcaoae sp. nov. for which both sexes are described, is assigned to the series pia while P. (P.) antioquiensis sp. nov., known only from the male, is included in the series verrucarum. The subgenus Pifanomyia is characterized and identification keys presented for the two new species.     

Identification of Plasmodium falciparum,P. vivax,P. ovale and P. malariae and detection of mixed infection in patients with imported malaria in Italy

The species-specific nested-PCR previously described by Snounou and others for detecting the four parasite species that cause human malaria is evaluated in the current study testing 230 blood samples. The results are compared with those obtained by microscopy and, for 101 samples out of 230, with those previously obtained by a genus-specific PCR based method (pg-PCR) followed by species-specific Southern-blot hybridization. All blood specimens were obtained from patients (127 foreigners and 103 Italians) with a suspect clinical diagnosis of imported malaria in Italy: 76 were positive by microscopy and 83 were positive by nested-PCR. The last method also revealed 10 double infections (8 foreigners and 2 Italians) which were not identified by microscopy or by pg-PCR with species-specific Southern-blot hybridization. Fifty-four out of 83 positive samples tested by nested-PCR were submitted to genomic sequence analysis, which confirmed the presence of DNA region portion encoding the 18S rRNA corresponding to the Plasmodium species identified by nested-PCR. These results demonstrate that the nested-PCR assay surpasses microscopy and pg-PCR with species-specific Southern-blot hybridization, both in sensitivity and in diagnostic accuracy. Moreover, it is quicker because it requires no further blotting or hybridization of PCR amplification products. This method also offers a clear advantage in the detection of mixed infections, which is important not only for successful medical treatment but also for the study of malaria epidemiology. Finally, our study also highlights the value of genomic sequence analysis for validating PCR results.     

Redescription of Nyssomyia intermedia (Lutz & Neiva, 1912) and Nyssomyia neivai (Pinto, 1926) (Diptera: Psychodidae)

The phlebotomine sand flies Nyssomyia intermedia and Nyssomyia neivai are the probable vectors of American tegumentary leishmaniasis in the Southern and Southeastern regions of Brazil. These species form a complex, being difficult to separate between either females or males of the two members based on recognized morphological characteristics. Both N. intermedia and N. neivai are redescribed here in the search for characters that facilitate their correct identification. It was possible to differentiate females by means of spermathecal characteristics. Males could be separated with confidence by the tips of the genital filaments, which have the form of a deep spoon, the angle of the concavity being well accentuated in N. intermedia and much shallower in N. neivai.     

<Emphasis Type="Italic">TRAF1/C5</Emphasis>polymorphism is not associated with increased mortality in rheumatoid arthritis: two large longitudinal studies

Introduction  

Recently an association between a genetic variation in TRAF1/C5 and mortality from sepsis or cancer was found in rheumatoid arthritis (RA). The most prevalent cause of death, cardiovascular disease, may have been missed in that study, since patients were enrolled at an advanced disease stage. Therefore, we used an inception cohort of RA patients to investigate the association between TRAF1/C5 and cardiovascular mortality, and replicate the findings on all-cause mortality. As TRAF1/C5 associated mortality may not be restricted to RA, we also studied a large cohort of non-RA patients.