[A national network of molecular tests to detect Chlamydia trachomatis and Neisseria gonorrhoeae: a pilot implementation experience in Brazil]. / Rede nacional de testes moleculares para detecção de Chlamydia trachomatis e Neisseria gonorrhoeae: experiência de implantação-piloto no Brasil.

This study aimed to know the opinion of professionals participating in an experiment to implement a pilot for molecular tests to detect Chlamydia trachomatis and Neisseria gonorrhoeae at the Brazilian Unified National Health System (SUS). The detection rate of C. trachomatis and/or N. gonorrhoeae and the factors associated with infection were determined. The strategy included laboratories belonging to the HIV and viral hepatitis viral load network. Testing targeted people who are more vulnerable to sexually transmitted infections and collected urine samples and/or vaginal, endocervical, and/or male urethral swabs. Questionnaires were sent to state managers and laboratory professionals about the implementation of the pilot. Reviews were overall positive. Weaknesses included difficulties changing work processes, lack of human resources, poorly sensitized care professionals, and absence of primary urine tubes, the only input not provided. Strengths included the centralized acquisition of tests, sharing of equipment, and storage of samples at room temperature. Of the 16,177 people who were tested, 1,004 (6.21%) were positive for C. trachomatis; 1,036 (6.4%), for N. gonorrhoeae; and 239 (1.48%), for C. trachomatis/N. gonorrhoeae . Detection of any infection occurred more frequently in young people (≤ 24 vs. > 24 years) (adjOR = 2.65; 95%CI: 2.38-2.96), men (adjOR = 1.95; 95%CI: 1.72-2.21), brown/black individuals (adjOR = 1.06; 95%CI: 1.05-1.11), those in Southeastern Brazil (adjOR = 1.08; 95%CI: 1.02-1.13), and in urethral secretion samples (adjOR = 1.46; 95%CI: 1.41-1.52). Results show the importance of making testing available nationwide, which supported the implementation of a definitive network to detection C. trachomatis/N. gonorrhoeae in SUS.

O objetivo deste estudo foi conhecer a opinião dos profissionais participantes da implantação-piloto de testes moleculares para detecção de Chlamydia trachomatis e Neisseria gonorrhoeae no Sistema Único de Saúde (SUS). Determinou-se a taxa de detecção de C. trachomatis e/ou N. gonorrhoeae e os fatores associados à infecção. A estratégia contou com laboratórios pertencentes à rede de carga viral de HIV e hepatites virais. A testagem teve como público-alvo pessoas mais vulnerabilizadas às infecções sexualmente transmissíveis, com coleta de amostras de urina e/ou swabs vaginal, endocervical e/ou uretral masculino. Questionários foram enviados aos gestores estaduais e profissionais de laboratório sobre a implantação-piloto. De maneira geral, as avaliações foram positivas. Entre as fraquezas, citou-se dificuldades na mudança do processo de trabalho, carência de recursos humanos, pouca sensibilidade de profissionais da assistência e ausência de tubo primário de urina, único insumo não fornecido. Como fortaleza, destaca-se aquisição centralizada de testes, compartilhamento de equipamentos e armazenamento de amostras à temperatura ambiente. Das 16.177 pessoas testadas, 1.004 (6,21%) foram positivas para C. trachomatis, 1.036 (6,4%) para N. gonorrhoeae e 239 (1,48%) para C. trachomatis/N. gonorrhoeae. A detecção de infecção ocorreu mais em pessoas jovens (≤ 24 vs. > 24 anos) (aOR = 2,65; IC95%: 2,38-2,96), do sexo masculino (aOR = 1,95; IC95%: 1,72-2,21), pardas/pretas (aOR = 1,06; IC95%: 1,05-1,11), na Região Sudeste (aOR = 1,08; IC95%: 1,02-1,13) e em amostras de secreção uretral (aOR = 1,46; IC95%: 1,41-1,52). Os resultados deste estudo demonstraram a importância da disponibilização da testagem em âmbito nacional, os quais subsidiaram a implantação da rede definitiva para detecção de C. trachomatis/N. gonorrhoeae no SUS.

El objetivo de este estudio fue conocer la opinión de los profesionales participantes de la implantación piloto de pruebas moleculares para la detección de Chlamydia trachomatis y Neisseria gonorrhoeae en el Sistema Único de Salud brasileño (SUS). Se determinó la tasa de detección de C. trachomatis y/o N. gonorrhoeae y los factores asociados con la infección. En la estrategia participaron laboratorios pertenecientes a la red de carga viral de VIH y hepatitis virales. La prueba tuvo como público objetivo a personas más vulnerables a las infecciones de transmisión sexual, con recolección de muestras de orina y/o swabs vaginal, endocervicales y/o uretral masculino. Se enviaron cuestionarios a los gestores estatales y a los profesionales de laboratorio sobre la implementación piloto. En general, las evaluaciones fueron positivas. Entre las debilidades, se citó las dificultades en el cambio del proceso de trabajo, la falta de recursos humanos, los profesionales de la asistencia poco sensibilizados y la ausencia del contenedor de orina primaria, el único insumo no suministrado. Como fortalezas, se destaca la adquisición centralizada de pruebas, el intercambio de equipos y el almacenamiento de muestras a temperatura ambiente. De las 16.177 personas evaluadas, 1.004 (6,21%) fueron positivas para C. trachomatis, 1.036 (6,4%) para N. gonorrhoeae y 239 (1,48%) para C. trachomatis/N. gonorrhoeae. La detección de alguna infección ocurrió más en personas jóvenes (≤ 24 vs. > 24 años) (aOR = 2,65; IC95%: 2,38-2,96), del sexo masculino (aOR = 1,95; IC95%: 1,72-2,21), parda/negra (aOR = 1,06; IC95%: 1,05-1,11), localizadas en la región Sudeste (aOR = 1,08; IC95%: 1,02-1,13) y en muestras de secreción uretral (aOR = 1,46; IC95%: 1,41-1,52). Los resultados de este estudio demostraron la importancia de la disponibilidad de la prueba a nivel nacional, los cuales subsidiaron la implantación de la red definitiva para detección de C. trachomatis/N. gonorrhoeae en el SUS.

Rede nacional de testes moleculares para detecção de Chlamydia trachomatis e Neisseria gonorrhoeae: experiência de implantação-piloto no Brasil / A national network of molecular tests to detect Chlamydia trachomatis and Neisseria gonorrhoeae: a pilot implementation experience in Brazil / Red nacional de pruebas moleculares para la detección de Chlamydia trachomatis y Neisseria gonorrhoeae: experiencia de implantación piloto en Brasil

Resumo: O objetivo deste estudo foi conhecer a opinião dos profissionais participantes da implantação-piloto de testes moleculares para detecção de Chlamydia trachomatis e Neisseria gonorrhoeae no Sistema Único de Saúde (SUS). Determinou-se a taxa de detecção de C. trachomatis e/ou N. gonorrhoeae e os fatores associados à infecção. A estratégia contou com laboratórios pertencentes à rede de carga viral de HIV e hepatites virais. A testagem teve como público-alvo pessoas mais vulnerabilizadas às infecções sexualmente transmissíveis, com coleta de amostras de urina e/ou swabs vaginal, endocervical e/ou uretral masculino. Questionários foram enviados aos gestores estaduais e profissionais de laboratório sobre a implantação-piloto. De maneira geral, as avaliações foram positivas. Entre as fraquezas, citou-se dificuldades na mudança do processo de trabalho, carência de recursos humanos, pouca sensibilidade de profissionais da assistência e ausência de tubo primário de urina, único insumo não fornecido. Como fortaleza, destaca-se aquisição centralizada de testes, compartilhamento de equipamentos e armazenamento de amostras à temperatura ambiente. Das 16.177 pessoas testadas, 1.004 (6,21%) foram positivas para C. trachomatis, 1.036 (6,4%) para N. gonorrhoeae e 239 (1,48%) para C. trachomatis/N. gonorrhoeae. A detecção de infecção ocorreu mais em pessoas jovens (≤ 24 vs. > 24 anos) (aOR = 2,65; IC95%: 2,38-2,96), do sexo masculino (aOR = 1,95; IC95%: 1,72-2,21), pardas/pretas (aOR = 1,06; IC95%: 1,05-1,11), na Região Sudeste (aOR = 1,08; IC95%: 1,02-1,13) e em amostras de secreção uretral (aOR = 1,46; IC95%: 1,41-1,52). Os resultados deste estudo demonstraram a importância da disponibilização da testagem em âmbito nacional, os quais subsidiaram a implantação da rede definitiva para detecção de C. trachomatis/N. gonorrhoeae no SUS.

Abstract: This study aimed to know the opinion of professionals participating in an experiment to implement a pilot for molecular tests to detect Chlamydia trachomatis and Neisseria gonorrhoeae at the Brazilian Unified National Health System (SUS). The detection rate of C. trachomatis and/or N. gonorrhoeae and the factors associated with infection were determined. The strategy included laboratories belonging to the HIV and viral hepatitis viral load network. Testing targeted people who are more vulnerable to sexually transmitted infections and collected urine samples and/or vaginal, endocervical, and/or male urethral swabs. Questionnaires were sent to state managers and laboratory professionals about the implementation of the pilot. Reviews were overall positive. Weaknesses included difficulties changing work processes, lack of human resources, poorly sensitized care professionals, and absence of primary urine tubes, the only input not provided. Strengths included the centralized acquisition of tests, sharing of equipment, and storage of samples at room temperature. Of the 16,177 people who were tested, 1,004 (6.21%) were positive for C. trachomatis; 1,036 (6.4%), for N. gonorrhoeae; and 239 (1.48%), for C. trachomatis/N. gonorrhoeae . Detection of any infection occurred more frequently in young people (≤ 24 vs. > 24 years) (adjOR = 2.65; 95%CI: 2.38-2.96), men (adjOR = 1.95; 95%CI: 1.72-2.21), brown/black individuals (adjOR = 1.06; 95%CI: 1.05-1.11), those in Southeastern Brazil (adjOR = 1.08; 95%CI: 1.02-1.13), and in urethral secretion samples (adjOR = 1.46; 95%CI: 1.41-1.52). Results show the importance of making testing available nationwide, which supported the implementation of a definitive network to detection C. trachomatis/N. gonorrhoeae in SUS.

Resumen: El objetivo de este estudio fue conocer la opinión de los profesionales participantes de la implantación piloto de pruebas moleculares para la detección de Chlamydia trachomatis y Neisseria gonorrhoeae en el Sistema Único de Salud brasileño (SUS). Se determinó la tasa de detección de C. trachomatis y/o N. gonorrhoeae y los factores asociados con la infección. En la estrategia participaron laboratorios pertenecientes a la red de carga viral de VIH y hepatitis virales. La prueba tuvo como público objetivo a personas más vulnerables a las infecciones de transmisión sexual, con recolección de muestras de orina y/o swabs vaginal, endocervicales y/o uretral masculino. Se enviaron cuestionarios a los gestores estatales y a los profesionales de laboratorio sobre la implementación piloto. En general, las evaluaciones fueron positivas. Entre las debilidades, se citó las dificultades en el cambio del proceso de trabajo, la falta de recursos humanos, los profesionales de la asistencia poco sensibilizados y la ausencia del contenedor de orina primaria, el único insumo no suministrado. Como fortalezas, se destaca la adquisición centralizada de pruebas, el intercambio de equipos y el almacenamiento de muestras a temperatura ambiente. De las 16.177 personas evaluadas, 1.004 (6,21%) fueron positivas para C. trachomatis, 1.036 (6,4%) para N. gonorrhoeae y 239 (1,48%) para C. trachomatis/N. gonorrhoeae. La detección de alguna infección ocurrió más en personas jóvenes (≤ 24 vs. > 24 años) (aOR = 2,65; IC95%: 2,38-2,96), del sexo masculino (aOR = 1,95; IC95%: 1,72-2,21), parda/negra (aOR = 1,06; IC95%: 1,05-1,11), localizadas en la región Sudeste (aOR = 1,08; IC95%: 1,02-1,13) y en muestras de secreción uretral (aOR = 1,46; IC95%: 1,41-1,52). Los resultados de este estudio demostraron la importancia de la disponibilidad de la prueba a nivel nacional, los cuales subsidiaron la implantación de la red definitiva para detección de C. trachomatis/N. gonorrhoeae en el SUS.

Innovative Pre-Clinical Data Using Peptides to Intervene in the Evolution of Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive, relentless, and deadly disease. Little is known about its pathogenetic mechanisms; therefore, developing efficient pharmacological therapies is challenging. This work aimed to apply a therapeutic alternative using immunomodulatory peptides in a chronic pulmonary fibrosis murine model. BALB/c mice were intratracheally instilled with bleomycin (BLM) and followed for 30 days. The mice were treated with the immune modulatory peptides ToAP3 and ToAP4 every three days, starting on the 5th day post-BLM instillation. ELISA, qPCR, morphology, and respiratory function analyses were performed. The treatment with both peptides delayed the inflammatory process observed in the non-treated group, which showed a fibrotic process with alterations in the production of collagen I, III, and IV that were associated with significant alterations in their ventilatory mechanics. The ToAP3 and ToAP4 treatments, by lung gene modulation patterns, indicated that distinct mechanisms determine the action of peptides. Both peptides controlled the experimental IPF, maintaining the tissue characteristics and standard function properties and regulating fibrotic-associated cytokine production. Data obtained in this work show that the immune response regulation by ToAP3 and ToAP4 can control the alterations that cause the fibrotic process after BLM instillation, making both peptides potential therapeutic alternatives and/or adjuvants for IPF.

An Overview on Immunogenic Cell Death in Cancer Biology and Therapy.

Immunogenic cell death (ICD) is a modality of regulated cell death that is sufficient to promote an adaptive immune response against antigens of the dying cell in an immunocompetent host. An important characteristic of ICD is the release and exposure of damage-associated molecular patterns, which are potent endogenous immune adjuvants. As the induction of ICD can be achieved with conventional cytotoxic agents, it represents a potential approach for the immunotherapy of cancer. Here, different aspects of ICD in cancer biology and treatment are reviewed.

Fish Oil Nanoemulsion Supplementation Attenuates Bleomycin-Induced Pulmonary Fibrosis BALB/c Mice.

Diets rich in omega-3 or -6 fatty acids will produce different profiles for cell membranes phospholipid constitutions. Omegas 3 and 6 are part of the diet and can modulate the inflammatory profile. We evaluated the effects of the oral absorption of fish oil, when associated with a lipid nanoemulsion in an experimental pulmonary inflammatory model. Pulmonary fibrosis is a disease associated with excessive extracellular matrix deposition. We determined to investigate the morphophysiological mechanisms in mice that were pretreated after induction with bleomycin (BLM). The pretreatment was for 21 days with saline solution, sunflower oil (SO), fish oil (FO), and fish oil nanoemulsion (NEW3). The animals received a daily dose of 50 mg/Kg of docosahexaenoic acid DHA and 10 mg/Kg eicosapentaenoic (EPA) (100 mg/Kg), represented by a daily dose of 40 µL of NEW3. The blank group was treated with the same amount daily (40 µL) during the 21 days of pretreatment. The animals were treated with SO and FO, 100 mg/Kg (containing 58 mg/Kg of polyunsaturated fats/higher% linoleic acid) and 100 mg/Kg (50 mg/Kg of DHA and 10 mg/Kg EPA), respectively. A single dose of 5 mg/mL (50 µL) bleomycin sulfate, by the intratracheal surgical method in BALB/cAnNTac (BALB/c). NEW3 significantly reduced fibrotic progression, which can be evidenced by the protection from loss of body mass, increase in respiratory incursions per minute, decreased spacing of alveolar septa, decreased severity of fibrosis, and changes in the respiratory system. NEW3 attenuated the inflammatory changes developed in the experimental model of pulmonary fibrosis, while group SO showed a significant increase in inflammatory changes. This concluded that the presented results demonstrated that is possible to positively modulate the immune and inflamamtory response to an external agressor, by changing the nutitional intake of specific fatty acids, such as omega-3 placed in fish oil. Moreover, these benefits can be improved by the nanoencapsulation of fish oil in lipid nanoemulsions.

The induction of immunogenic cell death by photodynamic therapy in B16F10 cells in vitro is effected by the concentration of the photosensitizer.

Photodynamic therapy (PDT) can trigger immune responses against cancer cells. The induction of immunogenic cell death (ICD) is one of the possible mechanisms behind this event, but the protocol conditions necessary for a robust induction of ICD by PDT have not been defined. In this work, the immunogenicity of B16F10 melanoma cells treated with different PDT protocols was investigated. The exposure of damage-associated molecules (DAMPs), namely HMGB1, calreticulin and ATP, a hallmark of ICD, and the presence of apoptotic and necrotic cells were assessed after the application of PDT mediated by different concentrations of aluminum-phthalocyanine (AlPcNE) in vitro. Furthermore, the in vivo immunogenicity of PDT-treated B16F10 cells was investigated with an immunization-challenge model in C57BL/6 mice. The percentage of dead cells was directly proportional to the concentration of AlPcNE. The IC50, IC70 and IC90 concentrations of AlPcNE induced the exposure of DAMPs by B16F10 cells after PDT. In the in vivo model, however, only the B16F10 cells treated with PDT-AlPcNE at the IC50 or IC70 rendered C57BL/6 significantly more resistant to a subsequent challenge with viable B16F10 cells. Thus, the induction of ICD in B16F10 cells by PDT occurs only at a specific range of AlPcNE concentrations.

Photodynamic therapy inhibits cell growth and enhances the histone deacetylase-mediated viability impairment in Cryptococcus spp. in vitro.

Cryptococcosis is a disseminated infection caused mainly by C. neoformans and C. gattii. Limitations for the treatment involve the selection of isolates resistant to conventional antifungal drugs, prolonged treatment time and drugs side effects. This study evaluated the combined effect of histone deacetylase inhibitors (HDACi) and photodynamic therapy (PDT) on the growth of C. neoformans and C. gattii in vitro. Results showed that PDT inhibited yeasts proliferation and enhanced the HDACi-mediated cell viability impairment in Cryptococcus spp.

The polysaccharide-rich tea of Ximenia americana barks prevents indomethacin-induced gastrointestinal damage via neutrophil inhibition.

ETHNOPHARMACOLOGICAL RELEVANCE: Barks of Ximenia americana are used by the population to treat gastrointestinal inflammatory disorders. Indomethacin is a non-selective non-steroidal anti-inflammatory drug that induces marked gastrointestinal damage. AIMS OF THE STUDIES: To evaluate the gastroprotective activity of total polysaccharides contained in the extract (TPL-Xa) or tea (Tea-Xa) of Ximenia americana barks in the mice gastric damage induced by indomethacin. MATERIALS AND METHODS: TPL-Xa was obtained by a combination of NaOH extraction and ethanol precipitation. Tea-Xa was prepared in distilled water boiled during 5 min. Animals received p.o. 0.9% NaCl (saline - control group), TPL-Xa (1-90 mg/kg) or Tea-Xa 1 h before gastritis induction by indomethacin (20 mg/kg). Mice were sacrificed 7 h after gastritis induction and analyzed for the following parameters: stomach lesions measurement; histological evaluation; myeloperoxidase (MPO) activity; nitrate/nitrite and cytokine levels; leukocyte adhesion and rolling by intravital microscopy. RESULTS: TPL-Xa reduced macroscopic and microscopic damage, MPO activity (59%), leukocyte rolling (86%) and adhesion (84%), nitrite/nitrate ratio (100%) and IL-8 (69%), but increased IL-4 (50%). Tea-Xa (12.8 yield; 39.3% carbohydrate, including 25.8% uronic acid; 4% protein) reduced macroscopic damage (62%) and MPO activity (50%). CONCLUSION: TPL and Tea of Ximenia americana barks ameliorate the gastric injury induced by indomethacin in mice, an effect that was dependent on the reduction of neutrophil infiltration.