Amphotericin B: an antifungal drug in nanoformulations for the treatment of paracoccidioidomycosis

La anfotericina B: una droga antifúngica en nanoformulaciones para el tratamiento de la paracoccidioidomicosisForma de citar: Pereira Garcia M, Meneses Almeida Santos MF, Saldanha Arruda C, Iocca DC. Amphotericin B: an antifungal drug in nanoformulations for the treatment of paracoccidioidomycosis. rev.univ.ind.santander.salud 2013; 45 (3): 45-53ABSTRACTThe use of magnetic nanoparticles (MNPs) in drug delivery vehicles must address issues such as drug-loading  capacity, desired  release profle,  aqueous dispersion  stability, biocompatibility with  cells  and tissue,  and  retention  of  magnetic  properties  after  interaction  with  macromolecules  or  modifcation via  chemical  reactions. Amphotericin  B  (AmB)  is  still  the  frst  choice  for  the  treatment  of  severe paracoccidioidomycosis, an important systemic fungal infection caused by Paracoccidoides brasiliensis. infortunately,  AmB  causes  acute  side  effects  (mainly  urinary  problems)  following  intravenous administration,  which  limits  its  clinical  use.  The  use  of  magnetic  nanoparticles  stabilized  with biocompatible substances, together with the possibility of their conjugation with drugs has become a new nanotechnological strategy in the treatment of diseases for drug delivery to specifc locations, such as the lungs in paracoccidoidiodomycosis. This review provides an overview of the disease, its etiologic agent and treatment with emphasis on the main strategies to improve the use of AmB in nanoformulations.Keywords:  Paracoccidioides brasiliensis;  amphotericin  B; magnetite  nanoparticles; magnetic  fuid; drug delivery complexRESUMENEl uso de nanopartículas magnéticas (MNPS) en los vehículos de suministro de fármacos debe abordar cuestiones como  la  capacidad  de  carga  de  las  drogas,  el  perfl  deseado  de  liberación,  estabilidad  de  la  dispersión  acuosa, biocompatibilidad  con  las  células,  tejidos  y  la  conservación  o  la modifcación  de  las  propiedades magnéticas después de la interacción con macromoléculas y/o reacciones químicas. La anfotericina B (AnB) continua siendo la primera opción para el tratamiento de la paracoccidioidomicosis grave, una importante infección sistémica causada por el hongo Paracoccidoides brasiliensis. Sin embargo, la AnB causa efectos secundarios agudos (principalmente problemas  urinarios)  tras  la  administración  intravenosa,  limitando  su  uso  clínico.  El  uso  de  nanopartículas magnéticas  estabilizadas  con  sustancias  biocompatibles  y  conjugadas  con  fármacos,  se  ha  convertido  en  una nueva estrategia nanotecnológica para el tratamiento de enfermedades en sitios específcos, como los pulmones en paracoccidoidiodomycosis. En esta revisión se hace una descripción general de la enfermedad, su agente etiológico y su tratamiento con énfasis en la principales estrategias para mejorar el uso de AnB en nanoformulaciones.Palabras clave:  Paracoccidioides brasiliensis,  anfotericina  B,  nanoparticulas  de magnetita;  fuido magnético; entrega controlada de medicamento

Amphotericin B: an antifungal drug in nanoformulations for the treatment of paracoccidioidomycosis

La anfotericina B: una droga antifúngica en nanoformulaciones para el tratamiento de la paracoccidioidomicosisForma de citar: Pereira Garcia M, Meneses Almeida Santos MF, Saldanha Arruda C, Iocca DC. Amphotericin B: an antifungal drug in nanoformulations for the treatment of paracoccidioidomycosis. rev.univ.ind.santander.salud 2013; 45 (3): 45-53ABSTRACTThe use of magnetic nanoparticles (MNPs) in drug delivery vehicles must address issues such as drug-loading  capacity, desired  release profle,  aqueous dispersion  stability, biocompatibility with  cells  and tissue,  and  retention  of  magnetic  properties  after  interaction  with  macromolecules  or  modifcation via  chemical  reactions. Amphotericin  B  (AmB)  is  still  the  frst  choice  for  the  treatment  of  severe paracoccidioidomycosis, an important systemic fungal infection caused by Paracoccidoides brasiliensis. infortunately,  AmB  causes  acute  side  effects  (mainly  urinary  problems)  following  intravenous administration,  which  limits  its  clinical  use.  The  use  of  magnetic  nanoparticles  stabilized  with biocompatible substances, together with the possibility of their conjugation with drugs has become a new nanotechnological strategy in the treatment of diseases for drug delivery to specifc locations, such as the lungs in paracoccidoidiodomycosis. This review provides an overview of the disease, its etiologic agent and treatment with emphasis on the main strategies to improve the use of AmB in nanoformulations.Keywords:  Paracoccidioides brasiliensis;  amphotericin  B; magnetite  nanoparticles; magnetic  fuid; drug delivery complexRESUMENEl uso de nanopartículas magnéticas (MNPS) en los vehículos de suministro de fármacos debe abordar cuestiones como  la  capacidad  de  carga  de  las  drogas,  el  perfl  deseado  de  liberación,  estabilidad  de  la  dispersión  acuosa, biocompatibilidad  con  las  células,  tejidos  y  la  conservación  o  la modifcación  de  las  propiedades magnéticas después de la interacción con macromoléculas y/o reacciones químicas. La anfotericina B (AnB) continua siendo la primera opción para el tratamiento de la paracoccidioidomicosis grave, una importante infección sistémica causada por el hongo Paracoccidoides brasiliensis. Sin embargo, la AnB causa efectos secundarios agudos (principalmente problemas  urinarios)  tras  la  administración  intravenosa,  limitando  su  uso  clínico.  El  uso  de  nanopartículas magnéticas  estabilizadas  con  sustancias  biocompatibles  y  conjugadas  con  fármacos,  se  ha  convertido  en  una nueva estrategia nanotecnológica para el tratamiento de enfermedades en sitios específcos, como los pulmones en paracoccidoidiodomycosis. En esta revisión se hace una descripción general de la enfermedad, su agente etiológico y su tratamiento con énfasis en la principales estrategias para mejorar el uso de AnB en nanoformulaciones.Palabras clave:  Paracoccidioides brasiliensis,  anfotericina  B,  nanoparticulas  de magnetita;  fuido magnético; entrega controlada de medicamento

Antifungal activity of amphotericin B conjugated to nanosized magnetite in the treatment of paracoccidioidomycosis

This study reports on in vitro and in vivo tests that sought to assess the antifungal activity of a newly developed magnetic carrier system comprising amphotericin B loaded onto the surface of pre-coated (with a double-layer of lauric acid) magnetite nanoparticles. The in vitro tests compared two drugs; i.e., this newly developed form and free amphotericin B. We found that this nanocomplex exhibited antifungal activity without cytotoxicity to human urinary cells and with low cytotoxicity to peritoneal macrophages. We also evaluated the efficacy of the nanocomplex in experimental paracoccidioidomycosis. BALB/c mice were intratracheally infected with Paracoccidioides brasiliensis and treated with the compound for 30 or 60 days beginning the day after infection. The newly developed amphotericin B coupled with magnetic nanoparticles was effective against experimental paracoccidioidomycosis, and it did not induce clinical, biochemical or histopathological alterations. The nanocomplex also did not induce genotoxic effects in bone marrow cells. Therefore, it is reasonable to believe that amphotericin B coupled to magnetic nanoparticles and stabilized with bilayer lauric acid is a promising nanotool for the treatment of the experimental paracoccidioidomycosis because it exhibited antifungal activity that was similar to that of free amphotericin B, did not induce adverse effects in therapeutic doses and allowed for a reduction in the number of applications

Metformin (dimethyl-biguanide) induced DNA damage in mammalian cells

Metformin (dimethyl-biguanide) is an insulin-sensitizing agent that lowers fasting plasma-insulin concentration, wherefore it's wide use for patients with a variety of insulin-resistant and prediabetic states, including impaired glucose tolerance. During pregnancy it is a further resource for reducing first-trimester pregnancy loss in women with the polycystic ovary syndrome. We tested metformin genotoxicity in cells of Chinese hamster ovary, CHO-K1 (chromosome aberrations; comet assays) and in mice (micronucleus assays). Concentrations of 114.4 µg/mL and 572 µg/mL were used in in vitro tests, and 95.4 mg/kg, 190.8 mg/kg and 333.9 mg/kg in assaying. Although the in vitro tests revealed no chromosome aberrations in metaphase cells, DNA damage was detected by comet assaying after 24 h of incubation at both concentrations. The frequency of DNA damage was higher at concentrations of 114.4 µg/mL. Furthermore, although mortality was not observed in in vitro tests, the highest dose of metformin suppressed bone marrow cells. However, no statistically significant differences were noted in micronuclei frequencies between treatments. In vitro results indicate that chronic metformin exposure may be potentially genotoxic. Thus, pregnant woman undergoing treatment with metformin should be properly evaluated beforehand, as regards vulnerability to DNA damage

Práticas de controle interno em cooperativas de crédito: análise sob a ótica de presidentes, conselheiros de administração e auditores internos

The study aimed to identify the perception of the Presidents, Board of Directors and internal auditors about the internal control practices in credit unions, based on the COSO ICIF 2013 framework. For this, a survey was used to capture the contexts institutional aspects of respondents. The data were analyzed together and by the means of the groups, using the Kruskal Wallis non-parametric test. The results indicate the existence of internal control practices in the institutions, however, there is no conceptual uniformity of internal control. In addition, the practices related to the components: Control environment and control activities, are more evident, however, the practices related to the other components need reinforcement to guarantee the constant functioning of the internal control system. In the general panorama, it is concluded that, despite the conceptual divergence, the cooperatives have internal control structures, being corroborated by the expressive agreement on the implementation of internal control practices.O estudo teve por objetivo identificar a percepção dos Presidentes, Conselheiros de Administração e Auditores internos acerca das práticas de controle interno em cooperativas de crédito, baseando-se no framework do COSO ICIF 2013. Para tanto, utilizou-se um survey para capturar os contextos institucionais dos respondentes. Os dados foram analisados em conjunto e pelas médias dos grupos, por meio do teste não paramétrico de Kruskal Wallis. Os resultados indicam a existência de práticas de controle interno nas instituições, todavia, não há uniformização conceitual de controle interno. Além disso, as práticas relacionadas aos componentes: Ambiente de controle e atividades de controle, são mais evidentes, todavia, as práticas relacionadas aos demais componentes necessitam de reforço para garantirem o funcionamento constante do sistema de controle interno. No panorama geral, conclui-se que, apesar da divergência conceitual, as cooperativas possuem estruturas de controles internos, sendo corroboradas pela expressiva concordância acerca da implementação de práticas de controle interno

Qualidade da atenção ao aborto no Sistema Único de Saúde do Nordeste brasileiro: o que dizem as mulheres? / Quality of abortion care in the Unified Health System of Northeastern Brazil: what do women say?

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2012-12-18T19:16:28Z No. of bitstreams: 1 Aquino, Estela Ml et al. Quality of abortion care in.pdf: 200501 bytes, checksum: cba72e306c5b8bc48f7f820a37508ea0 (MD5)Made available in DSpace on 2012-12-18T19:16:28Z (GMT). No. of bitstreams: 1 Aquino, Estela Ml et al. Quality of abortion care in.pdf: 200501 bytes, checksum: cba72e306c5b8bc48f7f820a37508ea0 (MD5) Previous issue date: 2012Universidade Federal da Bahia. Instituto de Saúde Coletiva. Salvador, BA, BrasilUniversidade Federal da Bahia. Instituto de Saúde Coletiva. Salvador, BA, BrasilUniversidade Federal de Pernambuco. Recife, PE, BrasilUniversidade Federal do Maranhão. São Luis, MA, BrasilUniversidade Federal de Pernambuco. Recife, PE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal da Bahia. Instituto de Saúde Coletiva. Salvador, Bahia, BrasilUniversidade Federal de Pernambuco. Recife, PE, BrasilUniversidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, BrasilUniversidade do Estado da Bahia. Salvador, BA, BrasilUniversidade Federal do Maranhão. São Luis, MA, BrasilLondon School of Hygiene and Tropical Medicine. Faculty of Epidemiology and Population Health. London, USAO aborto é grave problema de saúde no Brasil e suas complicações podem ser evitadas por atenção adequada e oportuna. O artigo avalia a qualidade da atenção às mulheres admitidas por aborto em hospitais do Sistema Único de Saúde, em Salvador, Recife e São Luís, tendo como referência as normas do Ministério da Saúde e o grau de satisfação das usuárias. Trata-se de inquérito com 2.804 usuárias, internadas por complicações do aborto em 19 hospitais, de agosto a dezembro de 2010. Considerou-se 4 dimensões - acolhimento e orientação, insumos/ambiente físico, qualidade técnica e continuidade do cuidado - desdobradas em critérios e indicadores. A adequação às normas foi maior quanto aos critérios de acolhimento e orientação. O apoio social e o direito à informação alcançaram valores baixos nas três cidades. A qualidade técnica do cuidado foi mal avaliada. Em insumos e ambiente físico, a limpeza foi o critério menos adequado. A situação é mais crítica na continuidade do cuidado nas 3 cidades, pela falta de consulta agendada de revisão, de informações sobre cuidados após alta hospitalar, risco de gravidez e planejamento familiar. A atenção ao aborto nessas cidades encontra-se distante do que propõem as normas brasileiras e os organismos internacionais.Abortion is a serious health problem in Brazil and complications can be avoided by adequate and timely care. The article evaluates the quality of care given to women admitted for abortion in hospitals operated by the Unified Health System, in Salvador, Recife and São Luis, the benchmarks being Ministry of Health norms and user satisfaction. The article analyzes 2804 women admitted to hospital for abortion complications in 19 hospitals, between August and December 2010. Four dimensions were defined: reception and guidance; inputs and physical environment; technical quality and continuity of care. There was a closer fit to norms on reception and guidance. Social support and the right to information were not well rated in all three cities. The technical quality of care was rated poor. With respect to inputs and physical environment, cleanliness was the least adequate criterion. Continuity of care was the most critical situation in all three cities, due to the lack of scheduled follow-up appointments, information about care available after hospital discharge, the risk of further pregnancy and family planning. Abortion care falls short of that advocated under Brazilian norms and by international agencies

Cancer survivorship needs in Brazil: Patient and family perspective.

IntroductionCancer Survivorship is a growing public health challenge. Effective responses from health care and social services depend on appropriate identification of survivors and their families´ specific needs. There are few studies on survivorship in low and middle-income countries, therefore, more evidence-based studies are necessary to develop a comprehensive approach to cancer survivorship.ObjectivesIdentify the needs of cancer survivors and their relatives, specifically those of individuals with breast, cervical or prostate cancer, and with acute lymphocytic leukemia (ALL).MethodsA qualitative, exploratory study conducted in two referral institutions in Brazil, located in Rio de Janeiro (Southeast region) and Fortaleza (Northeast region). The study included 47 patients of public and private health services and 12 family members. We used script-based semi-structured interviews. The discursive material obtained was categorized and analyzed using the Thematic Analysis approach.ResultsThe analysis identified three central themes: 1) consequences of cancer treatment; 2) Changes in daily life associated with cancer survivorship; and 3) Unmet structural needs in cancer survivorship.ConclusionSocial and cancer control policies in Brazil should provide resources, specific care standards and clinical, psychological and social support. Cancer survivors should also receive rehabilitation and work reintegration guidelines. This matter requires broader access to qualified cancer information, development of an integrated patient-centered care and care model, and more research resources for the country's post-treatment cancer period