Enzyme Responsive Delivery of Anti-Retroviral Peptide via Smart Hydrogel.

In response to an urgent need for advanced formulations for the delivery of anti-retrovirals, a stimuli-sensitive hydrogel formulation that intravaginally delivers HIV-1 entry inhibitor upon being exposed to a specific protease was developed. The hydrogel formulation consists of PEG-azide and PEG-DBCO covalently linked to the entry inhibitor peptide, enfuvirtide, via substrate linker that is designed to undergo proteolysis by prostate specific antigen (PSA) present in seminal fluid and release innate enfuvirtide. Of the tested PSA substrate linkers (HSSKLQYY, GISSFYSSK, AYLMYY, and AYLMGRR), HSSKLQ was found to be an optimal candidate for PEG-based hydrogel with kcat/KM of 2.2 M-1 s-1. The PEG-based hydrogel displayed a pseudoplastic, thixotropic behavior with overall viscosity varying between 1516 and 2.2 Pa.s, within the biologically relevant shear rates of 0.01-100 s-1. It also exhibited viscoelastic properties appropriate for uniform spreading and being retained in vagina. PEG-based hydrogels were loaded with N3-HSSKLQ-enfuvirtide (HF42) that is customarily synthesized enfuvirtide prodrug with its N-terminus connected to HSSKLQ linker. The stimuli-sensitive PEG-based hydrogel formulations upon being exposed to PSA released 36.5 ± 4.8% of enfuvirtide over 24 h in human ejaculate mimic of vaginal simulant fluid and seminal simulant fluid mixed in 1:3 ratio, which is significantly greater than its IC50. The PEG-based hydrogel was non-cytotoxic to both vaginal epithelial cells (VK2/E6E7) and murine macrophages (RAW 264.7) and did not significantly induce the production of nitric oxide, an inflammatory mediator. The PEG-based hydrogel is found to have suitable physicochemical properties for an intravaginal formulation of the PSA substrate-linked anti-retrovirals and is safe towards vaginal epithelium. It is capable of delivering enfuvirtide with effective concentrations to prevent women from HIV-1 infection.

COVID-19 en pediatría: aspectos clínicos, epidemiológicos, inmunopatogenia, diágnóstico y tratamiento / COVID-19 in Pediatrics: clinical and epidemiological aspects, immunopathogenesis, diagnostic and treatment

Introducción: La Organización Mundial de la Salud declaró desde el 11 de marzo de 2020 la infección por el coronavirus denominado SARS-CoV-2, como una pandemia, existente desde finales de 2019 en la provincia china de Wuhan. La enfermedad producida por este coronavirus se denomina COVID-19, entidad que ha mostrado una baja morbilidad y mortalidad en pediatría. Objetivo: Examinar factores epidemiológicos, sintomatología, diagnóstico y tratamiento de la enfermedad en la edad pediátrica. Métodos: Se revisó la literatura utilizando la base de datos PubMed para identificar artículos publicados hasta el 30 de abril 2020, informes, series de casos y datos de laboratorio. Resultados: La edad de presentación con mayor frecuencia ocurrió en los pacientes mayores de 5 años con 2,5 por ciento de casos graves, acompañados de fiebre, tos, congestión nasal, disnea, vómitos y diarreas como síntomas más frecuentes. Los datos de laboratorio indican una media de conteo leucocitario entre 6,1 y 6,8 × 105, linfopenia con rango entre 2,5 y 40 por ciento, y aumento de las enzimas alaniltranferasa y creatininfosfoquinasa, además del marcador antiinflamatorio proteína C reactiva, este último con concentraciones entre el 17 y 62,5 por ciento. La transmisión vertical no ha sido verificada. El tratamiento utilizado con mayor frecuencia es Lopinavir/ ritonavir e interferón. La radiografía de tórax fue normal entre el 20 y el 66 %. No se registran fallecidos en las seis series revisadas. Consideraciones finales: La infección por SARS-CoV-2 en pediatría evoluciona con un pronóstico favorable, pero se necesitan más investigaciones para un mejor conocimiento de la entidad(AU)

Introduction: The World Health Organization declared as a pandemic the infection by the coronavirus called SARS-CoV-2 on March 11th, 2020 that emerged in the last days of 2019 in the Chinese province of Wuhan. The disease produced by this coronavirus it is called COVID-19 and it is an entity that has shown low morbidity and mortality in pediatric patients. Objective: To examine epidemiological factors, symptomatology, diagnostic and treatment of the disease in pediatric ages. Methods: It was reviewed literature using PubMed database to identify articles published until April 30th, 2020, and also reports, series of cases and laboratory data. Results: The most frequent onset age was in patients older that 5 years, having 2,5% of seriously ill patients with fever, cough, nasal congestion, dyspnoea, vomiting and diarrhea as the most frequent symptoms. Laboratory data indicated a mean of leukocyte count between 6,1 and 6,8 x 105, lymphopenia with a range between 2,5 and 40 percent, and an increase of alaniltranferase and creatininfosfoquinase enzymes, in addition to the C reactive protein anti-inflammatory marker with concentrations between 17 and 62,5 percent. Vertical transmission has not been verified. The most frequently used treatment is Lopinavir/ ritonavir and interferon. Chest X-ray was normal in the 20 to 66 percent of the cases. No deaths were recorded in the six series of cases reviewed. Final considerations: The infection by SARS-CoV-2 in pediatric ages evolves with a favorable prognosis but more researches on the topic are needed for a best knowledge of this entity(AU)

COVID-19 en pediatría: aspectos clínicos, epidemiológicos, inmunopatogenia, diágnóstico y tratamiento / COVID-19 in Pediatrics: clinical and epidemiological aspects, immunopathogenesis, diagnostic and treatment

Introducción: La Organización Mundial de la Salud declaró desde el 11 de marzo de 2020 la infección por el coronavirus denominado SARS-CoV-2, como una pandemia, existente desde finales de 2019 en la provincia china de Wuhan. La enfermedad producida por este coronavirus se denomina COVID-19, entidad que ha mostrado una baja morbilidad y mortalidad en pediatría. Objetivo: Examinar factores epidemiológicos, sintomatología, diagnóstico y tratamiento de la enfermedad en la edad pediátrica. Métodos: Se revisó la literatura utilizando la base de datos PubMed para identificar artículos publicados hasta el 30 de abril 2020, informes, series de casos y datos de laboratorio. Resultados: La edad de presentación con mayor frecuencia ocurrió en los pacientes mayores de 5 años con 2,5 por ciento de casos graves, acompañados de fiebre, tos, congestión nasal, disnea, vómitos y diarreas como síntomas más frecuentes. Los datos de laboratorio indican una media de conteo leucocitario entre 6,1 y 6,8 × 105, linfopenia con rango entre 2,5 y 40 por ciento, y aumento de las enzimas alaniltranferasa y creatininfosfoquinasa, además del marcador antiinflamatorio proteína C reactiva, este último con concentraciones entre el 17 y 62,5 por ciento. La transmisión vertical no ha sido verificada. El tratamiento utilizado con mayor frecuencia es Lopinavir/ ritonavir e interferón. La radiografía de tórax fue normal entre el 20 y el 66 por ciento. No se registran fallecidos en las seis series revisadas. Consideraciones finales: La infección por SARS-CoV-2 en pediatría evoluciona con un pronóstico favorable, pero se necesitan más investigaciones para un mejor conocimiento de la entidad(AU)

Introduction: The World Health Organization declared as a pandemic the infection by the coronavirus called SARS-CoV-2 on March 11th, 2020 that emerged in the last days of 2019 in the Chinese province of Wuhan. The disease produced by this coronavirus it is called COVID-19 and it is an entity that has shown low morbidity and mortality in pediatric patients. Objective: To examine epidemiological factors, symptomatology, diagnostic and treatment of the disease in pediatric ages. Methods: It was reviewed literature using PubMed database to identify articles published until April 30th, 2020, and also reports, series of cases and laboratory data. Results: The most frequent onset age was in patients older that 5 years, having 2,5 percent of seriously ill patients with fever, cough, nasal congestion, dyspnoea, vomiting and diarrhea as the most frequent symptoms. Laboratory data indicated a mean of leukocyte count between 6,1 and 6,8 x 105, lymphopenia with a range between 2,5 and 40 percent, and an increase of alaniltranferase and creatininfosfoquinase enzymes, in addition to the C reactive protein anti-inflammatory marker with concentrations between 17 and 62,5 percent. Vertical transmission has not been verified. The most frequently used treatment is Lopinavir/ ritonavir and interferon. Chest X-ray was normal in the 20 to 66 percent of the cases. No deaths were recorded in the six series of cases reviewed. Final considerations: The infection by SARS-CoV-2 in pediatric ages evolves with a favorable prognosis but more researches on the topic are needed for a best knowledge of this entity(AU)

Highly Active Antiretroviral Therapy and Gamma Knife Radiosurgery for the Treatment of AIDS-Related Primary Central Nervous System Lymphoma.

BACKGROUND: The criterion standard for the treatment of newly diagnosed primary central nervous system lymphoma (PCNSL) remains high-dose chemotherapy in conjunction with palliative whole-brain radiotherapy; however, there may be a role for novel combined approaches in immunocompromised patients. CASE DESCRIPTION: A 66-year-old man presented with acute cephalalgia, disorientation, and lethargy. His condition was evaluated in the emergency department, and he was admitted with probable hydrocephalus. Magnetic resonance imaging (MRI) of the brain revealed multiple nonspecific brain lesions, predominantly involving the right temporal lobe, which on biopsy led to a diagnosis of PCNSL. Subsequent laboratory studies demonstrated active human immunodeficiency virus (HIV) infection, with a CD4 count of 21 cells/µL and an HIV viral load (VL) of >400,000 copies/mL. The patient was eventually given highly active antiretroviral therapy (HAART). He declined palliative whole-brain radiotherapy but was amenable to gamma knife radiosurgery (GKRS) for treatment of the right temporal brain lesions. Three months later, the patient's neurologic symptoms had improved; similarly, his CD4 count increased to 176 cells/mL, and his HIV viral load was <90 copies/mL. By the 12-month follow-up visit, the patient was asymptomatic, and at 36 months, MRI of the brain demonstrated total remission without new brain lesions. CONCLUSIONS: The criterion standard for treatment of newly diagnosed PCNSL remains high-dose chemotherapy in conjunction with palliative whole-brain radiotherapy; however, there may be a role for novel combined approaches using chemotherapy, HAART, and GKRS to have a positive impact on survival rates of PCNSL related to AIDS.

Snake bite in third trimester of pregnancy with systemic envenomation and delivery of a live baby in a low resource setting: A case report.

BACKGROUND: Snake bite in the third trimester of pregnancy with late presentation, systemic envenomation; disseminated intravascular coagulopathy and delivery of a live neonate is uncommon in a low resource setting. CASE: We present a 22 year old unbooked Gravida 3 Para 1+ 1 1alive lentiviral positive woman at 32 weeks gestation with snake bite, leg swelling, vaginal bleeding and labour pains. At presentation, there were anemia, tachycardia, hypotension; a gravid uterus with a single fetus in longitudinal lie, cephalic presentation, regular fetal heart rate and cervical dilatation of 3 cm. Preterm labour with antepartum hemorrhage due to venomous snake bite was diagnosed. Multidisciplinary management instituted led to the survival of both mother and baby. CONCLUSION: In resource constrained setting, disseminated intravascular coagulopathy arising from systemic envenomation due to snake bite in pregnancy could be challenging. Obstetric outcome depends on the degree of envenomation, gestational age at presentation, timing, duration and quality of treatment.

Antiretroviral manufacturers and the challenge of universal access to drugs through the Brazilian National STD/AIDS Program / As empresas produtoras de anti-retrovirais e o desafio do acesso universal aos medicamentos do Programa Nacional de DST e AIDS

This article describes the antiretroviral (ARV) manufacturing market in Brazil and contextualizes the challenges for the public policy of supplying ARVs through the National STD/AIDS Program. Increasing expenditure on these drugs is the main source of uncertainty for the policy's future. Brazil's domestic scenario is one of growing external dependence, both for the finished drugs and the active ingredients. Experience in the National Program has shown that it is the state's role to provide public goods, which presupposes ensuring mutual compatibility between company interests and social interests. This balance is currently at stake in Brazil, since structural changes in the market have raised challenges for the National Program's sustainability, requiring new public policy instruments in defense of the collective interest. The article drew on a literature review, using bibliographic indexing sources, systematic organization of primary data, government publications, relevant legislation, research reports, and articles recommended by experts from the field.

O artigo descreve as características do mercado produtor de anti-retrovirais no Brasil e situa os desafios para a política pública de provisão de medicamentos no Programa Nacional de DST e AIDS (PN-DST/AIDS). A elevação expressiva das despesas com esses medicamentos é a principal fonte de incerteza sobre a política. O cenário nacional é de crescente dependência externa, tanto no segmento de medicamentos quanto no de princípios ativos. A experiência do PN-DST/AIDS demonstrou que cabe ao Estado nacional a provisão de bens públicos, o que pressupõe a compatibilização entre interesses empresariais e sociais. Esse equilíbrio está sendo desafiado no Brasil visto que as mudanças estruturais no mercado trouxeram desafios à sustentabilidade do programa, exigindo novos instrumentos de política pública em defesa do interesse coletivo. Para a confecção do artigo empreendeu-se revisão da literatura usando-se fontes de indexação bibliográfica, sistematização de dados primários, publicações de órgãos públicos, legislações pertinentes, relatórios de pesquisa e artigos indicados por especialistas da área.

Mapping the body: tracing the personal and the political dimensions of HIV/AIDS in Khayelitsha, South Africa.

This article offers an analysis of the body-mapping dimension of the 'treatment literacy' initiatives of the Treatment Action Campaign (TAC), an HIV/AIDS-focused social movement in South Africa. It situates body mapping within the politics of HIV/AIDS activism in South Africa. The alliance between activists and biomedical practitioners is explored and the emphasis on the 'science of HIV' in TAC treatment literacy considered alongside the foregrounding of social realities, such as poverty and inequality. The article argues that the education activities of the TAC illustrate 'context-sensitive' science, rather than following a linear model of 'public understanding of science'. The personal accounts published alongside the first body maps are explored to illustrate an evident re-socialisation of biological organs and an emphasis on the relationality of bodies. The bounded bodies and the activist emphasis on body politics become ways to counteract fears of the virulence of the illness.