Ubiquitin-mediated protein degradation and methylation-induced gene silencing cooperate in the inactivation of the INK4/ARF locus in Burkitt lymphoma cell lines.

Burkitt lymphoma is one of the most aggressive tumors affecting humans. Together with the characteristic chromosomal translocation that constitutively activates the c-Myc oncogene, alterations in cellular tumor suppressor pathways are additionally required in order to allow the cells to overcome anti-oncogenic barriers and proliferate in an uncontrolled manner. The INK4a/ARF locus on chromosome 9p21 is considered a safeguard locus since it encodes the two important tumor suppressor proteins, p14 (ARF) and p16 (INK4a) . By regulating the p53 and Rb pathways p14 (ARF) and p16 (INK4a) respectively act as pro-apoptotic and cell cycle inhibitor proteins. The importance of the INK4a/ARF locus has been well documented in several human tumors as well as in Burkitt lymphoma. Although the mechanisms responsible for the transcriptional regulation of the INK4a/ARF locus have been thoroughly characterized, less is known about its posttranscriptional control. In this study we found that p16 (INK4a) and p14 (Arf) are concurrently inactivated in a panel of BL cell lines. We demonstrate that along with the epigenetic silencing of the p16INK4a gene, the complete inactivation of the locus is achieved by the improper turnover of INK4/ARF proteins by the ubiquitin-proteasome system (UPS), as the proteasome inhibitor MG-132 blocks p14 (ARF) degradation and induces a dramatic stabilization of the p16 (INK4a ) protein. We establish that the simultaneous deregulation of both DNA methylation patterns and the ubiquitin-dependent proteolysis system is required to completely inactive the INK4/ARF locus, opening new prospects for the understanding and treatment of Burkitt lymphoma.

Chagas disease: current epidemiological trends after the interruption of vectorial and transfusional transmission in the Southern Cone countries

Chagas disease, named after Carlos Chagas who first described it in 1909, exists only on the American Continent. It is caused by a parasite, Trypanosoma cruzi, transmitted to humans by blood-sucking triatomine bugs and by blood transfusion. Chagas disease has two successive phases, acute and chronic. The acute phase lasts 6 to 8 weeks. After several years of starting the chronic phase, 20% to 35% of the infected individuals, depending on the geographical area will develop irreversible lesions of the autonomous nervous system in the heart, esophagus, colon and the peripheral nervous system. Data on the prevalence and distribution of Chagas disease improved in quality during the 1980's as a result of the demographically representative cross-sectional studies carried out in countries where accurate information was not available. A group of experts met in Brasília in 1979 and devised standard protocols to carry out countrywide prevalence studies on human T. cruzi infection and triatomine house infestation. Thanks to a coordinated multi-country program in the Southern Cone countries the transmission of Chagas disease by vectors and by blood transfusion has been interrupted in Uruguay in1997, in Chile in 1999, and in 8 of the 12 endemic states of Brazil in 2000 and so the incidence of new infections by T. cruzi in the whole continent has decreased by 70%. Similar control multi-country initiatives have been launched in the Andean countries and in Central America and rapid progress has been recorded to ensure the interruption of the transmission of Chagas disease by 2005 as requested by a Resolution of the World Health Assembly approved in 1998. The cost-benefit analysis of the investments of the vector control program in Brazil indicate that there are savings of US$17 in medical care and disabilities for each dollar spent on prevention, showing that the program is a health investment with good return. Since the inception in 1979 of the Steering Committee on Chagas Disease of the Special Program for Research and Training in Tropical Diseases of the World Health Organization (TDR), the objective was set to promote and finance research aimed at the development of new methods and tools to control this disease. The well known research institutions in Latin America were the key elements of a world wide network of laboratories that received - on a competitive basis - financial support for projects in line with the priorities established. It is presented the time line of the different milestones that were answering successively and logically the outstanding scientific questions identified by the Scientific Working Group in 1978 and that influenced the development and industrial production of practical solutions for diagnosis of the infection and disease control.

Acute schistosomiasis outbreak in the metropolitan area of Belo Horizonte, Minas Gerais: alert about the risk of unnoticed transmission increased by growing rural tourism

The present article describes the occurrence of 17 cases of acute schistosomiasis in the metropolitan area of Belo Horizonte, state of Minas Gerais, Brazil. All individuals affected took a bath in a swimming pool of a holiday resort that was provided with water from a nearby brook. The apparently clean water and the absence of snails in the pool gave the wrong impression that there was no risk for infection. During a malacological survey at the site snails of the species Biomphalaria glabrata were found and tested positive for Schistosoma mansoni. All the patients live in the middle-class area of Barreiro, metropolitan area of Belo Horizonte and have medium grade school education. The difficulties in establishing the right diagnosis is expressed by the search for medical attention in 17 different medical facilities, the wide range of laboratory test and the inadequate treatment administration. A lack of knowledge about the disease was found in all groups studied. The booming rural tourism in endemic areas is identified as a probable risk factor for infection, especially for individuals of the non-immune middle and upper class parts of the society in urban centers. Special attention is given to a multidisciplinary approach to the complex issue of disease control and prevention.

Seasonal transmission of Leishmania (Leishmania) mexicana in the state of Campeche, Yucatan Peninsula, Mexico

In the Yucatan Peninsula, Mexico, localized cutaneous leishmaniasis (LCL) caused by Leishmania (Leishmania) mexicana is a typical wild zoonosis restricted to the forest, and humans are only accidentally involved. The transmission of L. (L.) mexicana has been related to the patient's occupation: "chicleros"(gum collectors) and agricultural workers. The objective of this study was to document L. (L.) mexicana seasonally of transmission in endemic areas of LCL in the state of Campeche, Yucatan Peninsula, Mexico. The timing of incidence of LCL in humans during 1993-1994, as well as the rate and time of infection in rodents and sand flies between February 1993 and March 1995 were analyzed. Rodents and sand flies were found infected between November and March, when men carried out their field activities and are exposed. Based on results analyzed, it is concluded that L. (L.) mexicana in the endemic area of LCL in the state of Campeche, Yucatan Peninsula, Mexico, presents a seasonal transmission restricted to the months of November to March. The knowledge of the timing of the transmission cycle in an endemic area of leishmaniasis is very important because intervention measures on the high-risk focus and population might be restricted.

Trends in drug consumption and risk of transmission of HIV and hepatitis C virus among injecting drug users in Switzerland, 1993-2006

As a part of the HIV behavioural surveillance system in Switzerland, repeated cross-sectional surveys were conducted in 1993, 1994, 1996, 2000 and 2006 among attenders of all low threshold facilities (LTFs) with needle exchange programmes and/or supervised drug consumption rooms for injection or inhalation in Switzerland. Data were collected in each LTF over five consecutive days, using a questionnaire that was partly completed by an interviewer and partly self administered. The questionnaire was structured around three topics: socio-demographic characteristics, drug consumption, health and risk/preventive behaviour. Analysis was restricted to attenders who had injected drugs during their lifetime (IDUs). Between 1993 and 2006, the median age of IDUs rose by 10 years. IDUs are severely marginalised and their social situation has improved little. The borrowing of used injection equipment (syringe or needle already used by other person) in the last six months decreased (16.5% in 1993, 8.9% in 2006) but stayed stable at around 10% over the past three surveys. Other risk behaviour, such as sharing spoons, cotton or water, was reported more frequently, although also showed a decreasing trend. The reported prevalence of HIV remained fairly stable at around 10% between 1993 and 2006; reported levels of hepatitis C virus (HCV) prevalence were high (56.4% in 2006). In conclusion, the overall decrease in the practice of injection has reduced the potential for transmission of infections. However as HCV prevalence is high this is of particular concern, as the current behaviour of IDUs indicates a potential for further spreading of the infection. Another noteworthy trend is the significant decrease in condom use in the case of paid sex.

Active transmission of human chagas disease in Colima Mexico

Despite efforts to eradicate American trypanosomiasis (AT) and Chagas disease from the Americas, there are still areas of active transmission that can eventually become a source of reinfection in previously controlled regions. Mexico could be one of those areas, where there are no formal preventive control programs despite the presence of communities infested by Triatominae bugs infected with Trypanosoma cruzi. This study explored the prevalence of T. cruzi infection in 405 habitants of 17 communities in the state of Colima, on the Pacific Mexican coast, through a seroepidemiological probabilistic survey. The results revealed a point seroprevalence of 2.4% positive for anti-T. cruzi. In addition, 2 clinical cases of chronic and 2 of acute Chagas disease were detected in the explored communities. These findings confirm the risk of active transmission of AT in Western Mexico, especially in rural and suburban communities infested with intra-domestic triatominae, where control programs should be implemented.

Phlebotomine sand flies in Porteirinha, an area of American visceral leishmaniasis transmission in the State of Minas Gerais, Brazil

A study of the phlebotomine sand fly fauna was carried out in an endemic area of American visceral leishmaniasis (AVL) in the municipality of Porteirinha, in the Brazilian state of Minas Gerais. Captures were performed with CDC light traps in 7 districts, 5 days per month, during 2 consecutive years (January 2000 to December 2001). A total of 3240 sand flies were captured and identified. Sixteen species were found, among which 15 belonged to the genus Lutzomyia and one to the genus Brumptomyia. Lutzomyia longipalpis, a proven vector of AVL, was the predominant species (71.85%) throughout the time period. The interference of climatic factors (temperature, humidity, and rainfall) over the populational dynamics of the sand flies was determined. Statistical analysis of the data showed a significant correlation among the number of phlebotomine sand flies collected, rainfall, and humidity, whereas the effect of temperature was negligible, in that particular region. The amount of collected phlebotomine, the number of human cases, and the prevalence of canine AVL in the districts of Porteirinha are discussed.

Alimentation et transmission mère-enfant

Bien que de nombreux auteurs aient traité, dans la relation mère-enfant, l'importance de l'alimentation, (et donc du rapport à la nourriture) et l'interprétation des troubles qui peuvent en résulter, nous proposons dans cet article de constituer une vérification expérimentale d'une question spécifique: que se transmet-il entre mère et enfant dans le contexte alimentaire ? Au travers d'une recherche multidisciplinaire alliant socio-anthropologie et psychologie, nous avons constitué et étudié un recueil de données couplant représentations socioculturelles, histoires alimentaires personnelles ainsi qu'observations et analyses de la qualité des interactions alimentaires auprès d'une population de mères françaises et leur enfant (sain) âgé de 1 à 2 ans.

The role of the scientific research in the control of schistosomiasis in endemic areas

The way the researches established the lines of direction for considering fight against schistosomiasis on the double aspect of transmission and morbidity control is outstanding. Chemotherapy in the morbidity control is emphasized. The research priorities for schistosomiasis control are mentioned.

Rural tourism as risk factor for the transmission of schistosomiasis in Minas Gerais, Brazil

Recently, the booming rural tourism in endemic areas of the state of Minas Gerais was identified as a contributing factor in the dissemination of the infection with Schistosoma mansoni. This article presents data from six holiday resorts in a rural district approximately 100 km distant from Belo Horizonte, MG, Brazil, where a possibly new and until now unperceived way of transmission was observed. The infection takes place in swimming pools and little ponds, which are offered to tourists and the local population for fishing and leisure activities. The health authorities of the district reported cases of schistosomiasis among the local population after visiting these sites. As individuals of the non-immune middle class parts of the society of big urban centers also frequent these resorts, infection of these persons cannot be excluded. A malacological survey revealed the presence of molluscs of the species Biomphalaria glabrata and Biomphalaria straminea at the resorts. The snails (B. glabrata) of one resort tested positive for S. mansoni. In order to resolve this complex problem a multidisciplinary approach including health education, sanitation measures, assistance to the local health services, and evolvement of the local political authorities, the local community, the tourism association, and the owners of the leisure resorts is necessary. This evidence emphasizes the urgent need for a participative strategic plan to develop the local tourism in an organized and well-administered way. Only so this important source of income for the region can be ensured on the long term without disseminating the disease and putting the health of the visitors at risk.

Lutzomyia longipalpis in Clorinda, Formosa province, an area of potential visceral leishmaniasis transmission in Argentina

Phlebotomine captures were performed during 2004 in Clorinda, Argentina. Clorinda is located across the branches of the Paraguay river in front of Asunción city, Paraguay. Reports of canine and human visceral leishmaniasis in Asunción have been increasing since 1997, however neither leishmaniasis cases nor sand flies were ever recorded from Clorinda. Light traps were located in migration paths (bridges, port), and peridomestic environments of Clorinda and surrounding localities. Lutzomyia longipalpis was found in Clorinda and Puerto Pilcomayo, first report in a potential visceral leishmaniasis transmission area for Argentina. Active surveillance is required immediately in the localities involved and the surrounding area.

Experimental infection of Leishmania (L.) chagasi in a cell line derived from Lutzomyia longipalpis (Diptera:Psychodidae)

The present work describes the in vitro infection of a cell line Lulo, derived from Lutzomyia longipalpis embryonic tissue, by Leishmania chagasi promastigotes. This infection process is compared with a parallel one developed using the J774 cell line. The L. chagasi MH/CO/84/CI-044B strain was used for experimental infection in two cell lines. The cells were seeded on glass coverslips in 24-well plates to reach a final number of 2 x 10(5) cells/well. Parasites were added to the adhered Lulo and J774 cells in a 10:1 ratio and were incubated at 28 and 37ºC respectively. After 2, 4, 6, 8, and 10 days post-infection, the cells were extensively washed with PBS, fixed with methanol, and stained with Giemsa. The number of internalized parasites was determined by counting at least 400 cultured cells on each coverslip. The results showed continuous interaction between L. chagasi promastigotes with the cell lines. Some ultrastructural characteristics of the amastigote forms were observed using transmission electron microscopy. The highest percentage of infection in Lulo cells was registered on day 6 post-infection (29.6%) and on day 4 in the J774 cells (51%). This work shows similarities and differences in the L. chagasi experimental infection process in the two cell lines. However, Lulo cells emerge as a new model to study the life-cycle of this parasite.

The importance of Anopheles albitarsis E and An. darlingi in human malaria transmission in Boa Vista, state of Roraima, Brazil

In several districts of Boa Vista, state of Roraima, Brazil we found Anopheles (Nyssorhynchus) albitarsis E to be the primary vector of human malaria parasites, and during 2001-2002 it was significantly more abundant than An. darlingi (p < 0.001). Other species sampled were An. (Nys.) braziliensis, An. (Ano.) peryassui, An. (Nys.) nuneztovari, An. (Nys.) oswaldoi s.l., and An. (Nys.) triannulatus. As determined by the ELISA technique An. darlingi had a higher overall infection rate (2.1%) compared with An. albitarsis E (1.2%). However, a marginally higher proportion of An. albitarsis E was infected with Plasmodium vivax compared with An. darlingi, and the An. albitarsis E biting index was also much higher. These results suggest the importance of An. albitarsis E in malaria transmission in a savannah ecoregion of northern Amazonian Brazil, and reconfirm the importance of An. darlingi even if at lower abundance.

Entre l'exemple et l'expérience: de la transmission par la famille d'une tradition à celle d'un ethos religieux

(Résumé de l'ouvrage) Les textes rassemblés dans cet ouvrage proposent diverses approches du phénomène religieux contemporain. Ils en montrent le caractère "flottant", les frontières incertaines. Ils font découvrir de nouveaux lieux vers lesquels s'oriente aujourd'hui une certaine quête de sens et de sacré. Ils pistent les dérives des grandes religions traditionnelles occidentales et les tentatives qu'entreprennent celles-ci pour freiner l'abandon qu'elles enregistrent ou - pire- l'indifférence qu'elle suscitent. Récusant tout autant "la mort de Dieu" que " le retour du religieux", les auteurs soulignent tous la complexité croissante de ce qu'on appelle couramment le religieux.