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We evaluated the importance of neutrophils in the development of chronic lesions caused by L. Viannia spp. using the hamster as experimental model of American Cutaneous Leishmaniasis (ACL). Neutrophils infiltrated the lesion within the first six hours post-infection. Inhibition of this early infiltration using a polyclonal antibody or cyclophosphamide was associated with transient parasite control but the protective effect vanished when lesions became clinically apparent. At lesion onset (approximately 10 days p.i.), there was an increased proportion of both uninfected and infected macrophages, and subsequently a second wave of neutrophils infiltrated the lesion (after 19 days p.i.) This second neutrophil infiltration was associated with lesion necrosis and ulceration (R2 = 0.75) and maximum parasite burden. Intradermal delivery of N-formylmethionyl-leucyl-phenylalanine (fMLP), aimed to increase neutrophil infiltration, resulted in larger lesions with marked necrosis and higher parasite burden than in mock treated groups (p<0.001 each). In contrast, reduced neutrophil infiltration via cyclophosphamide-mediated depletion led to more benign lesions and lower parasite loads compared to controls (p<0.001 each). Neutrophils of the second wave expressed significantly lower GM-CSF, reactive oxygen species and nitric oxide than those of the first wave, suggesting that they had less efficient anti-leishmania activity. However, there was increased inflammatory cytokines and expression of neutrophil proteases (myeloperoxidase, cathepsin G and elastase) in lesions during the second wave of neutrophil infiltration compared with the levels reached during the first wave (6h p.i.). This suggests that augmented neutrophil proteases and inflammatory cytokines during the secondary wave of neutrophils could contribute to skin inflammation, ulceration and necrosis in ACL. The overall results indicate that neutrophils were unable to clear the infection in this model, and that the second wave of neutrophils played an important role in the severity of ACL.

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In the early 2000s, receptor-interacting serine/threonine protein kinase 1 (RIPK1), a molecule already recognized as an important regulator of cell survival, inflammation and disease, was attributed an additional function: the regulation of a novel cell death pathway that came to be known as necroptosis. Subsequently, the related kinase RIPK3 and its substrate mixed-lineage kinase domain-like protein (MLKL) were also implicated in the necroptotic pathway, and links between this pathway and apoptosis were established. In this Timeline article, we outline the discoveries that have helped to identify the roles of RIPK1, RIPK3, MLKL and other regulators of necroptosis, and how they interact to determine cell fate.

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Necrolytic migratory erythema is a rare paraneoplastic dermatosis that may be the first clinical manifestation of the glucagonoma syndrome, a disorder characterized by mucocutaneous rash, glucose intolerance, hypoaminoacidemia, hyperglucagonaemia and pancreatic glucagonoma. The clinical case of a 45-year-old woman is presented. She had been experiencing weight loss, polydipsia, polyphagia, postprandial emesis, excessive hair loss and abdominal pain for two months. Erythematous, scaly and migratory plaques with 20 days of evolution were found on her trunk, perineum, elbows, hands, feet, inframammary and antecubital folds. The skin biopsy revealed noticeable vacuolar changes in high epidermal cells, extensive necrosis and thin orthokeratotic cornified layer. These findings pointed to a diagnosis of necrolytic migratory erythema. A suggestion was made to investigate a pancreatic glucagonoma. Laboratory tests showed moderate anemia, hyperglycemia and marked hyperglucagonaemia. Abdominal ultrasound revealed a mass in the tail of the pancreas measuring 6 x 5 x 5 cm which was resected. The histopathological findings were compatible with a diagnosis of glucagonoma, as confirmed by immunohistochemistry. Skin symptoms disappeared 10 days after the tumor resection. We can conclude that the histological changes defined may be clues that can lead the search for a distant skin disease and allow for its diagnosis. The histological pattern of vacuolation and epidermal necrosis should arouse suspicion of pancreatic glucagonoma.

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Under stress conditions, cells in living tissue die by apoptosis or necrosis depending on the activation of the key molecules within a dying cell that either transduce cell survival or death signals that actively destroy the sentenced cell. Multiple extracellular (pH, heat, oxidants, and detergents) or intracellular (DNA damage and Ca(2+) overload) stress conditions trigger various types of the nuclear, endoplasmic reticulum (ER), cytoplasmatic, and mitochondrion-centered signaling events that allow cells to preserve the DNA integrity, protein folding, energetic, ionic and redox homeostasis, thus escaping from injury. Along the transition from reversible to irreversible injury, death signaling is highly heterogeneous and damaged cells may engage autophagy, apoptotic, or necrotic cell death programs. Studies on multiple double- and triple- knockout mice identified caspase-8, flip, and fadd genes as key regulators of embryonic lethality and inflammation. Caspase-8 has a critical role in pro- and antinecrotic signaling pathways leading to the activation of receptor interacting protein kinase 1 (RIPK1), RIPK3, and the mixed kinase domain-like (MLKL) for a convergent execution pathway of necroptosis or regulated necrosis. Here we outline the recent discoveries into how the necrotic cell death execution pathway is engaged in many physiological and pathological outcome based on genetic analysis of knockout mice.

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O objetivo do presente trabalho foi relatar um caso clínico de necrose tecidual causada por alúmen de potássio. Paciente do sexo feminino realizou procedimento de enxerto de tecido conjuntivo para tratamento de defeito de rebordo classe I. Aos sete dias do período pós-operatório, observou-se extensa necrose da área receptora e do tecido enxertado. A paciente relatou que utilizou bochechos diários de alúmen de potássio para controle de edema e sangramento. O alúmen de potássio interferiu negativamente no processo de reparo tecidual.

The aim of this present study is to describe a case report of tissue necrosis caused by potassium alumina. Subepithelial connective tissue graft was used in the treatment of class I alveolar ridge defect. After seven days an extensive necrosis of the tissue graft and the receptor area was observed. The patient related that used potassium alumina solution as mouthrinse daily to control edema and bleeding. Potassium alumina had a negative influence in the tissue repair process.

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Programmed necrosis or necroptosis is an alternative form of cell death that is executed through a caspase-independent pathway. Necroptosis has been implicated in many pathological conditions. Genetic or pharmacological inhibition of necroptotic signaling has been shown to confer neuroprotection after traumatic and ischemic brain injury. Therefore, the necroptotic pathway represents a potential target for neurological diseases that are managed by neurosurgeons. In this review, we summarize recent advances in the understanding of necroptotic signaling pathways and explore the role of necroptotic cell death in craniocerebral trauma, brain tumors, and cerebrovascular diseases.

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Programmed necrosis or necroptosis is an alternative form of cell death that is executed through a caspase-independent pathway. Necroptosis has been implicated in many pathological conditions. Genetic or pharmacological inhibition of necroptotic signaling has been shown to confer neuroprotection after traumatic and ischemic brain injury. Therefore, the necroptotic pathway represents a potential target for neurological diseases that are managed by neurosurgeons. In this review, we summarize recent advances in the understanding of necroptotic signaling pathways and explore the role of necroptotic cell death in craniocerebral trauma, brain tumors, and cerebrovascular diseases.

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The present article investigates the role of Haitian community radios in strengthening social mobilization, with the aim of supporting the actions undertaken in the field of public health in Haiti, based on the development of the Workshop for community radios, as part of the Tripartite Cooperation Brazil-Cuba-Haiti. The qualitative methodology is justified because of the study content, an analysis of documents and direct observation, through a case study presented at the Workshop held in the department of Hinches, in Haiti. This meeting was held in the context of the Working Group on Tripartite Communication, under the responsibility of the Health Channel/Fiocruz, in partnership with the Department for Health Promotion and Environmental Prevention of the Ministry of Health and Population of Haiti (DPSPE/MSPP/Haiti), with a proposal to better structure a network of multipliers in health promotion.

O presente artigo investiga o papel das rádios comunitárias haitianas no fortalecimento da mobilização social com a finalidade de subsidiar as ações empreendidas no campo da saúde pública no Haiti a partir da construção e do desenvolvimento da Oficina para rádios comunitárias, no âmbito da Cooperação Tripartite Brasil-Cuba-Haiti. A metodologia de cunho qualitativo justifica-se pelo teor do estudo, de análise de documentos e da observação direta, mediante estudo de caso a partir da Oficina, realizada no departamento de Hinches, no Haiti. O encontro foi realizado no âmbito do Grupo de Trabalho de Comunicação da Tripartite, sob a responsabilidade do Canal Saúde/Fiocruz, em parceria com o Departamento de Promoção da Saúde e Prevenção do Meio Ambiente do Ministério da Saúde e População do Haiti (DPSPE/MSPP/Haiti), com a proposta de estruturar uma rede de multiplicadores de promoção da saúde.

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To investigate the blood vessels' concentration in TRAM flap's rat model, in the presence of pentoxifylline. 32 male, Wistar-EPM rats were divided into two groups. Control group (C): 0.5 ml of saline, intraperitoneally, once a day, for seven days before flap elevation; PTX group (P): pentoxifylline (20mg/kg/day), intraperitoneally, for seven days before flap elevation. After that, they were submitted to a caudal unipedicle TRAM flap. On the fifth postoperative day, percentages of flap necrosis were determined via the "paper template" method and Tram flap's zone IV skin biopsies were taken for histological analysis. The mean percentage of flap necrosis in group C was 58.7 % and in group P, 31.1 (Wilcoxon test; p = 0.003). Mean capillary vessels number in zone IV's skin in C group was 33.4 and in P group was 71.9 (p=0.008). Pentoxifylline was effective reducing the necrosis in the caudal unipedicle TRAM flap in the rat as well as increasing the number of capillaries in an ischemic zone (zone IV).(AU)

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Purpose: Clinical features in a case of acute retinal necrosis are described as well as its diagnostic approach and response to early treatment. Methods: This is a descriptive and retrospective study case report of a 26 year old male patient who arrived to the emergency room with a three day history of sudden visual loss in the right eye (RE). At initial evaluation a visual acuity of hand movements in the RE, 20/15 in the left eye (LE) and a right relative afferent pupillary defect were found. Fundoscopy revealed profuse soft exudates and hemorrhages involving posterior pole, inferior hemiretina and superotemporal periphery. Infectious workup and fluoresceinic angiography were made and positive serologies for herpes virus types 1 and 2, without HIV, were found. A diagnosis of acute retinal necrosis was made and treatment with intravenous valgancyclovir for two weeks and intra-vitreous triamcinolone for severe vasculitis, was given. Then a 3 months treatment with oral antiviral agents was prescribed. Results: Patient’s evolution showed improvement with treatment and at two and a half months of follow up, visual acuity was 20/50 in the right eye, normal slit lamp examination, tonometry of 12 mm Hg and fundoscopy improved when compared to initial pictures. Conclusions: A high index of suspicion is needed for diagnosing ARN taking into account clinical findings. Prompt intravenous and intra-vitreous treatments are needed to achieve good clinical and functional outcomes and to avoid central nervous system complications.

Objetivo: Describir un caso de necrosis retiniana aguda, las características clínicas, el enfoque diagnóstico y la respuesta al tratamiento. Método: Se realiza un estudio descriptivo, retrospectivo tipo informe de caso en un paciente de sexo masculino, 26 años de edad, que consulta al Servicio de Urgencias con historia de pérdida visual del ojo derecho (OD) de 3 días de evolución. Al examen de ingreso se encontró una agudeza visual del OD de movimiento de manos y defecto pupilar aferente, y 20/15 en el ojo izquierdo (OI). En el estudio del fondo de ojo derecho se encontraron exudados blandos abundantes y hemorragias que comprometen todo el polo posterior, la hemirretina inferior y la periferia supero temporal. En los exámenes para clínicos se evidenciaron serologías positivas para herpes tipo 1 y 2 en ausencia de VIH y a la angiografía con fluoresceína cambios vasculares con zonas de no perfusión. Se llega al diagnóstico de necrosis retiniana aguda y se decide manejar con valganciclovir endovenoso durante dos semanas, triamcinolona intravítrea y fotocoagulación retiniana con laser para el manejo de la vasculitis severa y zonas isquémicas; luego se continuó con antivirales orales por 3 meses. Resultados: Después de 2 meses y medio de seguimiento, hay una agudeza visual de 20/50 del OD, un examen biomicroscópico normal, presión intraocular de 12 mm Hg y el fondo de ojo muestra mejoría del cuadro al compararlo con las fotos iniciales.Conclusiones: Al diagnóstico de NRA se llega con la sospecha clínica, de acuerdo con los signos del examen; se requiere un manejo endovenoso e intravítreo oportuno, para lograr buenos resultados tanto clínicos como funcionales y evitar complicaciones a nivel del sistema nervioso central.

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