How to structure an oncogenetics service for the public health system: Report of the implementation of the first service in Northeastern Brazil.

INTRODUCTION: Identifying carriers of genetic mutations that increase the risk of developing cancer allows to adopt timely risk-reducing strategies. However, due to the elevated cost of genetic testing, few oncogenetics services are available in the Brazilian public health care system, especially in economically disadvantaged areas. OBJECTIVE: To describe the implementation of an oncogenetics service for patients suspected of hereditary cancer syndromes (HBOC and HNPCC) at a philanthropic referral oncology hospital in Northeastern Brazil, funded by the Ministry of Health's National Oncology Care Support Program (PRONON). METHODS: The service was implemented with the PDCA method (Plan, Do, Check and Act). RESULTS: During the first year of operation (starting in August 2018), 675 individuals were examined, of whom 272 patients and 98 family members were submitted to genetic testing. This included the collection of 338 DNA samples of which 300 were sequenced. The analysis identified 48 (17.1%) mutations for HBOC and 19 (6.8%) for HNPCC. CONCLUSION: In one year, the oncogenetics service was able to benefit over 300 families by generating advanced molecular data which may be used for tailoring cancer prevention and management.

How does genetic testing influence anxiety, depression, and quality of life? A hereditary breast and ovarian cancer syndrome suspects trial.

BACKGROUND: Emotional distress associated with genetic testing for hereditary breast and ovarian cancer syndrome (HBOC) is reported to interfere with adherence to treatment and prophylactic measures and compromise quality of life. OBJECTIVES: To determine levels of anxiety, depression, and quality of life in patients tested for pathogenic BRCA1/2 mutations and identify risk factors for the development of adverse psycho-emotional effects. METHODS: Cross-sectional observational trial involving 178 breast or ovarian cancer patients from a referral cancer hospital in Northeastern Brazil. Information was collected with the Hospital Anxiety and Depression Scale (HADS) and the World Health Organization (WHO) Quality of Life (QoL) questionnaire (WHOQOL-BREF). RESULTS: Patients suspected of HBOC had higher levels of anxiety than depression. The presence of (probably) pathogenic BRCA1/2 mutations did not affect levels of anxiety and depression. High schooling, history of psychiatric disease, and use of psychotropic drugs were directly associated with high anxiety. High schooling was too inversely associated with QoL as such a breast tumor. Anxiety and depression were directly correlated and both reduced significantly QoL. CONCLUSION: Our results highlight the importance of psychological support and screening of risk factors for anxiety and depression and low QoL in HBOC patients at the time of testing.

Processo formativo de enfermeiros: visão de egressos sobre prática e inserção no mundo do trabalho / Proceso de formación del enfermero: visión de los egresados sobre la práctica y la inserción en el mundo laboral / Nurses' training process: graduates' point of view on practice and insertion in the world of work

RESUMO Objetivo: identificar as potencialidades do processo formativo de enfermeiros a partir da visão dos egressos sobre sua prática profissional e inserção no mundo do trabalho. Método: estudo descritivo, exploratório, com abordagem quanti-qualitativa. Participaram do estudo 198 (68,5%) egressos de um curso de Enfermagem do sul de Minas Gerais que responderam a um formulário eletrônico enviado por plataforma digital. Foram realizadas análise estatística descritiva e análise temática. Resultados: os egressos indicaram como potencialidades da sua formação a tradição institucional da universidade, a capacitação docente, a facilidade de relacionamento professor-aluno e a experiência com atividades extracurriculares. Referiram satisfação com a profissão, mas destacaram que a remuneração está a quém das responsabilidades assumidas no trabalho, com consequente desvalorização profissional. Indicaram temas que podem ser fortalecidos durante o percurso acadêmico para inserção profissional, como ampliar a carga horária prática, aperfeiçoar o entrosamento entre academia e preceptoria dos serviços de saúde, fortalecer o ensino de gestão/gerenciamento, autonomia, liderança e tomada de decisão, empoderamento profissional, entre outros. Demonstraram a importância de se prepararem para o trabalho na própria vivência laboral e por meio da educação permanente. Considerações Finais: pesquisas com egressos permitiram avaliar o processo de formação, sendo relevantes para o planejamento e readequação das políticas de educação. Manter políticas de acompanhamento e um canal de comunicação efetivo com os egressos para o seguimento de sua trajetória contribui para que o currículo seja continuamente revisto e reformulado na dinâmica do processo formativo, facilitando a transição entre a academia e o mundo do trabalho.

RESUMEN Objetivo: identificar las potencialidades del proceso de formación de los enfermeros a partir de la visión de los egresados sobre su práctica profesional e inserción en el mundo laboral. Método: estudio descriptivo, exploratorio, con enfoque cuantitativo y cualitativo. Participaron del estudio 198 (68,5%) egresados de un curso de Enfermería en el Sur de Minas Gerais, quienes respondieron un formulario electrónico enviado por plataforma digital. Se realizó análisis estadístico descriptivo y análisis temático. Resultados: los egresados señalaron como potencialidades formativas la tradición institucional de la Universidad, la capacitación docente, la facilidad de relación profesor-alumno y la experiencia con las actividades extracurriculares. Mencionaron satisfacción con la profesión, pero destacaron que la remuneración está por debajo de las responsabilidades asumidas en el trabajo, con la consiguiente devaluación profesional. Indicaron temas que pueden fortalecerse durante la trayectoria académica para la inserción profesional, como extender la carga práctica, mejorar la relación entre la academia y la preceptoría de los servicios de salud, fortalecer la enseñanza de la gestión, la autonomía, el liderazgo y la toma de decisiones, el empoderamiento profesional, entre otros. Demuestran la importancia de prepararse para el trabajo en su propria experiencia laboral y mediante la educación permanente. Consideraciones finales: la investigación con egresados permite evaluar el proceso de formación, siendo relevante para la planificación y reajuste de las políticas educativas. Mantener políticas de seguimiento y un canal de comunicación eficaz con los egresados para seguir su trayectoria contribuye a que el currículo sea continuamente revisado y reformulado en la dinámica del proceso formativo, facilitando la transición entre la academia y el mundo laboral

ABSTRACT Objective: to identify the potentialities of the nurses' training process based on the graduates' point of view of their professional practice and insertion in the world of work. Method: a descriptive, exploratory study with a quantitative and qualitative approach. One-hundred ninety-eight (68.5%) graduates of a Nursing course in the south of Minas Gerais participated in the study and answered an electronic form sent by digital platform. Descriptive statistical analysis and thematic analysis were performed. Results: the graduates indicated the university's institutional tradition, teacher training, ease of teacher-student relationship and experience with extracurricular activities as potential training opportunities. They mentioned satisfaction with the profession but highlighted that the remuneration is below the responsibilities assumed at work, with consequent professional devaluation. They indicated themes that can be strengthened during the academic path for professional insertion, such as extending the practical workload, improving the relationship between the academy and the preceptorship of healthcare services, strengthening management/management teaching, autonomy, leadership, and decision making, empowerment professional, among others. They demonstrated the importance of preparing for work in their own work experience and through permanent education. Final Considerations: research with graduates allowed to evaluate the training process, being relevant for the planning and readjustment of education policies. Maintaining follow-up policies and an effective communication channel with graduates to follow their trajectory contributes to the curriculum being continuously reviewed and reformulated in the dynamics of the training process, facilitating the transition between academia and the world of work.

Side-Effects of Irinotecan (CPT-11), the Clinically Used Drug for Colon Cancer Therapy, Are Eliminated in Experimental Animals Treated with Latex Proteins from Calotropis procera (Apocynaceae).

Intestinal mucositis (IM) is the critical side effect of irinotecan (CPT-11), which is the front-line drug used for the treatment of colorectal cancer. This study aimed to evaluate the effectiveness of latex proteins (LP) from Calotropis procera to prevent IM and diarrhea in animals. Swiss mice were treated daily with saline or LP (1, 5, or 50 mg/kg, i.v.) 24 h prior to CTP-11 (75 mg/kg/4 days, i.p) and for additional 6 days. Animal survival, body weight variation, and diarrhea were registered. After animal sacrifice (day 7 post first injection of CPT-11), intestinal samples were collected to study morphology and inflammatory parameters. Animals given LP exhibited improved parameters (survival, body weight, and absence of diarrhea) as compared with the CPT-11 control. The severity of IM observed in animals given CPT-11 was reduced in animals treated with LP. Treatment with LP also prevented the reduction in the villus/crypt ratio promoted by CPT-11. The rise in MPO activity and pro-inflammatory cytokines, over-contractility of the smooth muscle, and diarrhea were all abrogated in LP-treated mice. Markedly reduced immunostaining intensity for COX-2, TNF-α, IL-1ß, iNOS, and NF-κB was observed in the intestinal tissue of animals treated with LP. The side-effects of CPT-11 were eliminated by LP treatment in experimental animals and improved clinical parameters characteristic of IM All known biochemical pathogenesis. Copyright © 2016 John Wiley & Sons, Ltd.

Protein fraction of Calotropis procera latex protects against 5-fluorouracil-induced oral mucositis associated with downregulation of pivotal pro-inflammatory mediators.

Oral mucositis is an important dose-limiting and costly side effect of cancer chemotherapy. Soluble proteins obtained of the latex of Calotropis procera have been extensively characterized as anti-inflammatory in different experimentally induced inflammatory conditions, including arthritis and sepsis. In this study, the phytomodulatory laticifer proteins (LP) were challenged to regress the inflammatory events associated with 5-fluorouracil-induced oral mucositis. We also evaluated the expression of pro-inflammatory cytokines and inducible enzymes, such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Oral mucositis was induced in hamsters by two injections of 5-fluorouracil (5-FU; 60 and 40 mg/kg, i.p., on experimental days 1 and 2, respectively). LP (5 mg/kg, i.p.) was injected 24 h before and 24 h after mechanical trauma of the cheek pouches. A normal control group received only saline. On day 10, the animals were sacrificed, and the cheek pouches were excised for macroscopic and histopathological analysis, myeloperoxidase activity measurement, and immunohistochemical assessment of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), iNOS, and COX-2. LP significantly inhibited macroscopic histopathological scores and myeloperoxidase activity compared with the 5-FU control group. 5-Fluorouracil also induced marked immunostaining of TNF-α, IL-1ß, iNOS, and COX-2 on inflamed conjunctive and epithelial tissue compared with the normal control group. Such damage was significantly inhibited (p < 0.05) by LP treatment compared with the 5-FU group. These findings demonstrate an anti-inflammatory effect of LP on 5-FU-induced oral mucositis. The protective mechanism appears to involve inhibition of the expression of iNOS, COX-2, TNF-α, and IL-1ß.

In vitro and in vivo antitumor effects of (4-methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone.

PURPOSE: (4-Methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone (PHT) is a phenstatin analog compound. PHT is a known tubulin inhibitor that has potent cytotoxic activity. In the present study, PHT was synthesized and its antitumor activity was determined using in vitro and in vivo experimental models. METHODS: The in vitro cytotoxic activity of the PHT was determined by the MTT assay. The antimitotic and hemolytic effects were determined based on the inhibition of sea urchin embryo development and lysis of mouse erythrocytes, respectively. In vivo antitumor activity was assessed in mice inoculated with sarcoma 180 cells. RESULTS: In vitro, PHT displayed cytotoxicity in tumor cell lines, showing IC(50) values in the nanomolar range. In addition, it inhibited sea urchin embryo development during all phases examined, first and third cleavage and blastula stage. However, PHT did not induce hemolysis using mouse erythrocytes, suggesting that the cytotoxicity of PHT does not involve membrane damage. The in vivo study demonstrated tumor inhibition rates of 30.9 and 48.2% for PHT at doses of 20 and 40 mg/kg, respectively. In addition, PHT was also able to increase the response elicited by 5-fluorouracil (5-FU) from 33.3 to 55.7%. The histopathological analysis of liver, kidney, and spleen showed that they were just moderately affected by PHT treatment. Neither enzymatic activity of transaminases nor urea levels were significantly affected. Hematological analysis showed leukopenia after 5-FU treatment, but this effect was prevented when 5-FU was combined with PHT. CONCLUSIONS: In conclusion, PHT exhibited in vitro and in vivo antitumor effects without substantial toxicity.

Agglutinin isolated from the red marine alga Hypnea cervicornis J. Agardh reduces inflammatory hypernociception: involvement of nitric oxide.

Hypnea cervicornis agglutinin (HCA), a lectin isolated from the red marine alga has been previously shown to have an antinociceptive effect. In the present study in rats, mechanisms of action of HCA were addressed regarding mechanical hypernociception induced by carrageenan, ovalbumin (as antigen), and also by prostaglandin E(2) in rats. The lectin administered intravenously inhibited carrageenan- and antigen-induced hypernociception at 1, 3, 5 and 7h. This inhibitory effect was completely prevented when lectin was combined with mucin, demonstrating the role of carbohydrate-binding sites. The inhibition of inflammatory hypernociception by HCA was associated with the prevention of neutrophil recruitment to the plantar tissue of rats but was not associated with the inhibition of the release of pro-hypernociceptive cytokines (TNF-alpha, IL-1 beta and CINC-1). HCA also blocked mechanical hypernociception induced by PGE(2), which was prevented by the administration of nitric oxide synthase inhibitors. These results were corroborated by the increased circulating levels of NO metabolites following HCA treatment. These findings suggest that the anti-hypernociceptive effects of HCA are not associated with the inhibition of pro-inflammatory cytokine production. However, these effects seem to involve the inhibition of neutrophil migration and also the increase in NO production.

Involvement of NO in the inhibitory effect of Calotropis procera latex protein fractions on leukocyte rolling, adhesion and infiltration in rat peritonitis model.

AIM OF THE STUDY: The latex of Calotropis procera has been used in the traditional medicinal system for the treatment of leprosy, ulcers, tumors, piles and diseases of liver, spleen, abdomen and toothache. It comprises of a non-dialyzable protein fraction (LP) that exhibits anti-inflammatory properties and a dialyzable fraction (DF) exhibiting pro-inflammatory properties. The present study was carried out to evaluate the effect of LP sub-fractions on neutrophil functions and nociception in rodent models and to elucidate the mediatory role of nitric oxide (NO). MATERIAL AND METHODS: The LP was subjected to ion exchange chromatography and the effect of its three sub-fractions (LP(PI), LP(PII) and LP(PIII)) thus obtained was evaluated on leukocyte functions in the rat peritonitis model and on nociception in the mouse model. RESULTS: LP sub-fractions exhibit distinct protein profile and produce a significant decrease in the carrageenan and DF induced neutrophil influx and exhibit anti-nociceptive property. The LP and its sub-fractions produced a marked reduction in the number of rolling and adherent leukocytes in the mesenteric microvasculature as revealed by intravital microscopy. The anti-inflammatory effect of LP(PI), the most potent anti-inflammatory fraction of LP, was accompanied by an increase in the serum levels of NO. Further, our study shows that NO is also involved in the inhibitory effect of LP(PI) on neutrophil influx. CONCLUSIONS: Our study shows that LP fraction of Calotropis procera comprises of three distinct sets of proteins exhibiting anti-inflammatory and anti-nociceptive properties of which LP(PI) was most potent in inhibiting neutrophil functions and its effects are mediated through NO production.

Antinociceptive activity and toxicology of the lectin from Canavalia boliviana seeds in mice.

The aim of the present study was to evaluate the potential antinociceptive and toxicity of Canavalia boliviana lectin (CboL) using different methods in mice. The role of carbohydrate-binding sites was also investigated. CboL given to mice daily for 14 days at doses of 5 mg/kg did not cause any observable toxicity. CboL (1, 5, and 10 mg/kg) administered to mice intravenously inhibited abdominal constrictions induced by acetic acid and the two phases of the formalin test. In the hot plate and tail immersion tests, the same treatment of CboL induced significant increase in the latency period. In the hot plate test, the effect of CboL (5 mg/kg) was reversed by naloxone (1 mg/kg), indicating the involvement of the opioid system. In the open-field and rota-rod tests, the CboL treatment did not alter animals' motor function. These results show that CboL presents antinociceptive effects of both central and peripheral origin, involving the participation of the opioid system via lectin domain.

Pharmacological analysis of the neutrophil migration induced by D. rostrata lectin: involvement of cytokines and nitric oxide.

In the present study, we investigated the involvement of resident cell and inflammatory mediators in the neutrophil migration induced by chemotactic activity of a glucose/mannose-specific lectin isolated from Dioclea rostrata seeds (DrosL). Rats were injected i.p. with DrosL (125-1000 microg/cavity), and at 2-96 h thereafter the leukocyte counts in peritoneal fluid were determined. DrosL-induced a dose-dependent neutrophil migration accumulation, which reached maximal response at 24 h after injection and declines thereafter. The carbohydrate ligand nearly abolished the neutrophil influx. Pre-treatment of peritoneal cavities with thioglycolate which increases peritoneal macrophage numbers, enhanced neutrophil migration induced by DrosL by 303%. However, the reduction of peritoneal mast cell numbers by treatment of the cavities with compound 48/80 did not modify DrosL-induced neutrophil migration. The injection into peritoneal cavities of supernatants from macrophage cultures stimulated with DrosL (125, 250 and 500 microg/ml) induced neutrophil migration. In addition, DrosL treatment induced cytokines (TNF-alpha, IL-1beta and CINC-1) and NO release into the peritoneal cavity of rats. Finally, neutrophil chemotaxis assay in vitro showed that the lectin (15 and 31 microg/ml) induced neutrophil chemotaxis by even 180%. In conclusion, neutrophil migration induced by D. rostrata lectin occurs by way of the release of NO and cytokines such as IL-1beta, TNF-alpha and CINC-1.

Vascular permeability, neutrophil migration and edematogenic effects induced by the latex of Cryptostegia grandiflora.

Inflammatory responses have been described as occurring after exposure to some latex materials. In this study pro-inflammatory activity in the latex of Cryptostegia grandiflora was investigated. The soluble proteins of the latex (CgLP) were isolated from the whole latex and evaluated by in vivo assays. CgLP induced strong inflammatory activity mediated by neutrophil migration, enlarging vascular permeability and increasing myeloperoxidase activity locally in rats. CgLP-induced inflammation was observed in peritonitis, paw edema and air push models. In addition, CgLP caused hyperemia in a healing model. The peritonitis effect was lost when CgLP was previously boiled suggesting the involvement of pro-inflammatory proteins. Thioglycollate increased the neutrophil migration induced by CgLP, but not by fMLP. Mast cell depletion provoked by 40/80 compound did not modify the course of inflammation triggered by CgLP, being similar to fMLP, which suggested that neutrophil migration was induced by direct mechanism mediated by macrophages. Neutrophil migration stimulated by CgLP was strongly inhibited by Dexamethasone and to a lesser extent by Thalidomide, indicating the involvement of cytokines in mediating neutrophil infiltration. Celecoxib and Indomethacin were inhibitory suggesting the involvement of prostaglandins. Cimetidine was effective only in the initial phase of edema. PCA 4248 was ineffective. It is concluded that the latex of C. grandiflora is a potent inflammatory fluid, and also that laticifer proteins may be implicated in this process.

Antinociceptive and anti-inflammatory effects of a mucin-binding agglutinin isolated from the red marine alga Hypnea cervicornis.

The agglutinin from the red marine alga Hypnea cervicornis (HCA) was tested in models of nociception and inflammation. The role of carbohydrate-binding sites and the systemic toxicity were assessed. HCA (10(-1), 1, and 10 mg/kg) administered i.v. to mice inhibited writhes induced by acetic acid and, at 10 mg/kg, inhibited the second phase of the formalin test, but did not alter the response latency in the hot-plate test. HCA (1 mg/kg) administered i.v. to rats reduced carrageenan-induced paw edema at 1, 2, and 3 h after challenge, but not edema induced by dextran. The neutrophil migration induced by both N-formyl-methionyl-leucyl-phenylalanine (fMLP) and carrageenan was inhibited by HCA at 10(-1), 1, and 10 mg/kg. The combination of HCA (1 mg/kg) and its ligand mucin reversed the lectin inhibitory effect on carrageenan-induced neutrophil migration and acetic acid-induced writhes. The i.v. treatment of rats with HCA (1 mg/kg) for 7 days did not affect body mass; liver, kidney or heart wet weight; blood leukocyte counts; urea, creatinine or serum transaminase activity; or macroscopy of the organs examined. In short, H. cervicornis agglutinin showed important antinociceptive and anti-inflammatory activity via interaction with the lectin carbohydrate-binding site.