The anticancer drug tamoxifen is active against Trypanosoma cruzi in vitro but ineffective in the treatment of the acute phase of Chagas disease in mice

The activity of the antineoplastic drug tamoxifen was evaluated against Trypanosoma cruzi. In vitro activity was determined against epimastigote, trypomastigote and amastigote forms of CL14, Y and Y benznidazole resistant T. cruzi strains. Regardless of the strain used, the drug was active against all life-cycle stages of the parasite with a half maximal effective concentration ranging from 0.7-17.9 µM. Two experimental models of acute Chagas disease were used to evaluate the in vivo efficacy of treatment with tamoxifen. No differences in parasitemia and mortality were observed between control mock-treated and tamoxifen-treated mice.FAPESPFIOCRUZCNP

Fractal dimension of large aggregates under different flocculation conditions

The two-dimensional fractal dimension (Df) of large aggregates of kaolin (> 540 μm) during the shear flocculation process for kaolin solution was investigated using non-intrusive in situ image-based acquisition system. Separate experiments were also carried out for three different sized sub-ranges of large aggregates (0.540–1.125 mm; 1.125–1.750 mm; 1.750–2.375 mm). Digital images were taken at a frequency of 10 Hz for 10 s for each different pairs of gradients of velocity (Gf) of 20 and 60 s− 1 and flocculation times of 2; 3; 4; 5; 10; 20; 30; 60; 120 and 180 min. For the same conditions, particle size distribution (PSD) was also determined. Under the investigated conditions, the lowest Gf produced the greatest Df (1.69) at a flocculation time of 30 min for the whole range of aggregates. Also, the evolution of the longest length of aggregate (l) and Df with time, showed that the dynamic steady-state was reached at different times for each shear rate and l ranges. However, Df varied for each size sub-range (ca. 1.1 to 1.8). Finally, the behavior of the aggregate structure may be understood by the predominance of different aggregation mechanisms such as cluster-cluster for Gf of 60 s− 1 and particle-cluster for Gf of 20 s− 1

Prevalence of Oral Pain and Barriers to use of Emergency Oral Care Facilities Among Adult Tanzanians.

Oral pain has been the major cause of the attendances in the dental clinics in Tanzania. Some patients postpone seeing the dentist for as long as two to five days. This study determines the prevalence of oral pain and barriers to use of emergency oral care in Tanzania. Questionnaire data were collected from 1,759 adult respondents aged 18 years and above. The study area covered six urban and eight rural study clusters, which had been selected using the WHO Pathfinder methodology. Chi-square tests and logistic regression analyses were performed to identify associations.\ud Forty two percent of the respondents had utilized the oral health care facilities sometimes in their lifetime. About 59% of the respondents revealed that they had suffered from oral pain and/or discomfort within the twelve months that preceded the study, but only 26.5% of these had sought treatment from oral health care facilities. The reasons for not seeking emergency care were: lack of money to pay for treatment (27.9%); self medication (17.6%); respondents thinking that pain would disappear with time (15.7%); and lack of money to pay for transport to the dental clinic (15.0%). Older adults were more likely to report that they had experienced oral pain during the last 12 months than the younger adults (OR = 1.57, CI 1.07-1.57, P < 0.001). Respondents from rural areas were more likely report dental clinics far from home (OR = 5.31, CI = 2.09-13.54, P < 0.001); self medication at home (OR = 3.65, CI = 2.25-5.94, P < 0.001); and being treated by traditional healer (OR = 5.31, CI = 2.25-12.49, P < 0.001) as reasons for not seeking emergency care from the oral health care facilities than their counterparts from urban areas. Oral pain and discomfort were prevalent among adult Tanzanians. Only a quarter of those who experienced oral pain or discomfort sought emergency oral care from oral health care facilities. Self medication was used as an alternative to using oral care facilities mainly by rural residents. Establishing oral care facilities in rural areas is recommended

Developments on drug discovery and on new therapeutics: highly diluted tinctures act as biological response modifiers

<p>Abstract</p> <p>Background</p> <p>In the search for new therapies novel drugs and medications are being discovered, developed and tested in laboratories. Highly diluted substances are intended to enhance immune system responses resulting in reduced frequency of various diseases, and often present no risk of serious side-effects due to its low toxicity. Over the past years our research group has been investigating the action of highly diluted substances and tinctures on cells from the immune system.</p> <p>Methods</p> <p>We have developed and tested several highly diluted tinctures and here we describe the biological activity of M1, M2, and M8 both <it>in vitro </it>in immune cells from mice and human, and <it>in vivo </it>in mice. Cytotoxicity, cytokines released and NF-κB activation were determined after <it>in vitro </it>treatment. Cell viability, oxidative response, lipid peroxidation, bone marrow and lymph node cells immunophenotyping were accessed after mice <it>in vivo </it>treatment.</p> <p>Results</p> <p>None of the highly diluted tinctures tested were cytotoxic to macrophages or K562. Lipopolysaccharide (LPS)-stimulated macrophages treated with all highly diluted tinctures decreased tumour necrosis factor alpha (TNF-α) release and M1, and M8 decreased IFN-<it>γ </it>production. M1 has decreased NF-κB activity on TNF-α stimulated reporter cell line. <it>In vivo </it>treatment lead to a decrease in reactive oxygen species (ROS), nitric oxide (NO) production was increased by M1, and M8, and lipid peroxidation was induced by M1, and M2. All compounds enhanced the innate immunity, but M1 also augmented acquired immunity and M2 diminished B lymphocytes, responsible to acquired immunity.</p> <p>Conclusions</p> <p>Based on the results presented here, these highly diluted tinctures were shown to modulate immune responses. Even though further investigation is needed there is an indication that these highly diluted tinctures could be used as therapeutic interventions in disorders where the immune system is compromised.</p

The Pioneer Anomaly

Radio-metric Doppler tracking data received from the Pioneer 10 and 11 spacecraft from heliocentric distances of 20-70 AU has consistently indicated the presence of a small, anomalous, blue-shifted frequency drift uniformly changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was interpreted as a constant sunward deceleration of each particular spacecraft at the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of the Newton's gravitational inverse-square law has become known as the Pioneer anomaly; the nature of this anomaly remains unexplained. In this review, we summarize the current knowledge of the physical properties of the anomaly and the conditions that led to its detection and characterization. We review various mechanisms proposed to explain the anomaly and discuss the current state of efforts to determine its nature. A comprehensive new investigation of the anomalous behavior of the two Pioneers has begun recently. The new efforts rely on the much-extended set of radio-metric Doppler data for both spacecraft in conjunction with the newly available complete record of their telemetry files and a large archive of original project documentation. As the new study is yet to report its findings, this review provides the necessary background for the new results to appear in the near future. In particular, we provide a significant amount of information on the design, operations and behavior of the two Pioneers during their entire missions, including descriptions of various data formats and techniques used for their navigation and radio-science data analysis. As most of this information was recovered relatively recently, it was not used in the previous studies of the Pioneer anomaly, but it is critical for the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living Reviews in Relativit

Primary healthcare and the construction of thematic health networks: what role can they play?

The enhancement of primary healthcare has been a core strategy for the empowerment of the Brazilian Unified Health System (SUS). Recent guidelines issued by OPAS and the Ministry of Health highlight the role it has played as a thematic communication network center, a regulating agent for the access and use of services required for comprehensive healthcare. Sponsored by PPSUS/Fapesp, this study examines the possibilities of the primary healthcare network exercising such a strategic function. Life narratives involving 15 regular users were produced in two cities of ABC Paulista, which have adopted the Family Health Strategy for the organization of their primary healthcare networks. The study presents three main findings: the primary healthcare network serves as an outpost of SUS by producing user values even for high complexity service users; the primary network is perceived is a place for simple care needs; there is shared impotence between users and teams when it comes to the network functioning as the coordinator of care, indicating that it does not possess the technological, operational and organizational material conditions or symbolic conditions (values, meanings, and representations) to be in a central position in the coordination of thematic healthcare networks.O fortalecimento da atenção básica tem sido valorizado como estratégia central para a construção do SUS. Diretrizes recentes emanadas pela OPAS e pelo MS destacam seu papel como centro de comunicação de redes temáticas, como reguladora do acesso e utilização dos serviços necessários para a integralidade do cuidado. O presente estudo, financiado com recursos PPSUS/Fapesp, problematiza as possibilidades da rede básica exercer tal função estratégica. Foram produzidas narrativas de vida de 15 usuários altamente utilizadores de serviços de saúde em dois municípios do ABC paulista, que adotaram a Estratégia de Saúde da Família para organização de suas redes básicas. O estudo apresenta três achados principais: a rede básica funciona como posto avançado do SUS, produzindo valores de uso mesmo para os pacientes utilizadores de serviços de alta complexidade; a rede básica é vista como lugar de coisas simples; há uma impotência compartilhada entre usuários e equipes quando se trata da rede básica funcionar como coordenadora do cuidado, indicando como ela não reúne condições materiais (tecnológicas, operacionais, organizacionais) e simbólicas (valores, significados e representações) de deter a posição central da coordenação das redes temáticas de saúde.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de Medicina PreventivaInstituto Superior de Ciências do Trabalho e da Empresa Instituto Universitário de Lisboa Faculdade de Ciências Médicas Departamento de Saúde ColetivaUniversidade Estadual de Campinas Faculdade de Ciências Médicas Departamento de Saúde ColetivaUNIFESP, EPM, Depto. de Medicina PreventivaSciEL

Tri-n-butyltin Hydride-Mediated Radical Reactions of ortho- and meta-Iodobenzamides to Synthesize Benzomacrolactams. Surprising Formation of Biphenyl Compounds from meta-Regioisomers

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Reactions of methyl 4-O-allyl-2,3-di-O-benzyl-6-deoxy-6-(3-iodobenzoylamino)-alpha-D-galactopyranoside, its gluco epimer, methyl 2,3-di-O-benzyl-6-deoxy-6-(3-iodobenzoylamino)4-O-(1-pentenyl)-alpha-D-glucopyranoside and its ortho-regioisomer with tri-n-butyltin hydride were performed in different conditions. Depending on reaction conditions the three meta-iodo isomers gave a surprising amount of biphenyl compounds. The 2-iodo isomer led only to the undesired but expected hydrogenolysis product. No cyclized products were isolated in all the reactions. The structures of the new biphenyl products were elucidated by (1)H and (13)C NMR spectroscopy, DEPT, COSY, HMQC and HMBC experiments and ESI-MS/MS. Mechanisms for the formation of these new biphenyl derivatives and hypotheses to explain the different outcomes for radical reactions of 3- or 2-iodobenzamides were presented.20815041514Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Discovery of Markers of Exposure Specific to Bites of Lutzomyia longipalpis, the Vector of Leishmania infantum chagasi in Latin America

Leishmania parasites are transmitted by the bite of an infected vector sand fly that injects salivary molecules into the host skin during feeding. Certain salivary molecules can produce antibodies and can be used as an indicator of exposure to a vector sand fly and potentially the disease it transmits. Here we identified potential markers of specific exposure to the sand fly Lutzomyia longipalpis, the vector of visceral leishmaniasis in Latin America. Initially, we determined which of the salivary proteins produce antibodies in humans, dogs, and foxes from areas endemic for the disease. To identify potential specific markers of vector exposure, we produced nine different recombinant salivary proteins from Lu. longipalpis and tested for their recognition by individuals exposed to another human-biting sand fly, Lu. intermedia, that transmits cutaneous leishmaniasis and commonly occurs in the same endemic areas as Lu. longipalpis. Two of the nine salivary proteins were recognized only by humans exposed to Lu. longipalpis, suggesting they are immunogenic proteins and may be useful in epidemiological studies. The identification of specific salivary proteins as potential markers of exposure to vector sand flies will increase our understanding of vector–human interaction, bring new insights to vector control, and in some instances act as an indicator for risk of acquiring disease