Necrólisis epidérmica tóxica en una adolescente diagnosticada de trastorno bipolar II y tratada con lamotrigina / Toxic epidermal necrolysis in an adolescent with Bipolar Disorder II and treated with Lamotrigine

Resumen La necrólisis epidérmica tóxica es una enfermedad cutánea severa, la mayoría de las veces desencadenada como reacción adversa a medicamentos, con alta morbilidad y mortalidad. La lamotrigina, junto a otros medicamentos estabilizadores del ánimo, constituye la causa medicamentosa más frecuente de esta complicación, consistente en necrosis y esfacelo de la epidermis y mucosas en más del 30 % de la superficie corporal, con la consecuente pérdida de líquidos y electrolitos, respuesta inflamatoria sistémica, susceptibilidad a infecciones y hasta sepsis, además de posibles secuelas ominosas. En la actualidad, el diagnóstico de trastorno bipolar se hace con mayor frecuencia, incluyendo al grupo etario de niños y adolescentes, pero tal proceso diagnóstico se caracteriza por dificultades y controversias en mayor cuantía que otros diagnósticos psiquiátricos. Ello obliga a una meticulosa elucubración diagnóstica y selección farmacológica, con pleno conocimiento de las moléculas del arsenal medicamentoso para, en caso de prescripción de lamotrigina, establecer una escrupulosa psicoeducación al paciente y sus familiares además de un seguimiento estricto y cercano. A propósito del caso de una adolescente diagnosticada de trastorno bipolar II, que recibió lamotrigina durante un episodio depresivo pero con un esquema posológico inadecuado, y desarrolló necrólisis epidérmica tóxica, revisamos y comentamos la literatura correspondiente. Concluimos en que es preciso extremar las precauciones al decidir el uso de lamotrigina para minimizar el riesgo de este severo efecto adverso.

Toxic epidermal necrolysis is a severe skin disease, most often triggered as an adverse drug reaction, with high morbidity and mortality. Lamotrigine, together with other mood stabilizer drugs, constitutes the most frequent drug that causes this complication, which consists of necrosis and detachment of the epidermis and mucosa in more than 30% of the body surface, with the consequent loss of water and electrolytes, systemic inflammatory response, susceptibility to infections and even sepsis, in addition to other possible ominous sequelae. Currently, the diagnosis of bipolar disorder is made more frequently, including the age group of children and adolescents, but such a diagnostic process is characterized by difficulties and controversies to a greater extent than other psychiatric diagnoses. This requires meticulous diagnostic process and pharmacological selection, with full knowledge of the molecules in the drug arsenal so, in case of lamotrigine prescription, it should be established scrupulous psychoeducation to the patient and their family members, as well as strict and close follow-up. A propos of the case of an adolescent girl diagnosed with bipolar II disorder, who received lamotrigine during a depressive episode but with an inappropriate posology, and developed toxic epidermal necrolysis, we reviewed and commented on the corresponding literature. We conclude that extreme caution is necessary when deciding the use of lamotrigine to minimize the risk of this severe adverse effect.

Renal histological alterations induced by acute exposure of titanium dioxide nanoparticles / Alteraciones histológicas renales inducidas por la exposición aguda de nanopartículas de dióxido de titanio

SUMMARY: Titanium dioxide nanoparticles (TiO2 NPs) are widely used in many commercial products, nanomedicine, agriculture, personal care products, different industries and pharmaceutical preparations with potential risk in human health and the environment. The current work was conducted to investigate the renal damage that might be induced by the acute toxicity TiO2 NPs. A total of 40 healthy male adult Wistar albino rats (Rattus norvegicus) were exposed to TiO2 NPs (126, 252, 378 mg/kg bw) for 24 and 48 h. Fresh portions of the kidneys from each rat were processed for histological and histochemical alterations. In comparison with respective control rats, exposure to TiO2 NPs has marked the following glomerular, tubular and interstitial alterations including the followings: glomerular congestion, Bowman's capsule swelling and dilatation, inflamed glomeruli, renal tubules cloudy swelling, karyorrhexis, karyolysis, infiltration of inflammatory cells, congestion, necrosis, hydropic degeneration, dilatation and congestion of blood vessels, hyaline droplets and hyaline casts precipitation, interstitial edema and fibrosis. From the findings of the current work one may conclude that TiO2 NPs are capable of inducing kidney damage with more insulation in the cortex and the proximal convoluted tubules than the medulla and the distal ones respectively. In addition, it might be concluded that renal damage induced by these nanomaterials is dose and duration of exposure dependent. Further hematological, biochemical, immunohistochemical, and ultra-structural studies are recommended.

RESUMEN: Las nanopartículas de dióxido de titanio (TiO2 NP) se usan ampliamente en muchos productos comerciales, nanomedicina, agricultura, productos para el cuidado personal, diferentes industrias y preparaciones farmacéuticas con riesgo potencial para la salud humana y el medio ambiente. El trabajo actual se realizó para investigar el daño renal que podría ser inducido por la toxicidad aguda NP de TiO2. Un total de 40 ratas Wistar albinas adultas sanas (Rattus norvegicus) fueron expuestas a TiO2 NP (126, 252, 378 mg / kg de peso corporal) durante 24 y 48 h. Las muestras de los riñones de las ratas se procesaron para estudios histológicos e histoquímicos. En comparación con las ratas control, la exposición de las ratas a TiO2 NP presentaron las siguientes alteraciones glomerulares, tubulares e intersticiales: congestión glomerular, dilatación de la cápsula de Bowman, inflamación glomerular, túbulos renales aumentados, cariorrexis, cariólisis, infiltración de células inflamatorias, congestión, necrosis, degeneración hidrópica, dilatación y congestión de vasos sanguíneos, gotas y precipitaciones hialina, edema intersticial y fibrosis. A partir de los hallazgos del trabajo actual, se puede concluir que las NP de TiO 2 son capaces de inducir daño renal con más aislamiento en la corteza y en los túbulos contorneados proximales que en la médula y los túbulos contorneados distales, respectivamente. Además, se podría concluir que el daño renal inducido por estos nanomateriales depende de la dosis y la duración de la exposición. Se recomiendan estudios adicionales hematológicos, bioquímicos, inmunohistoquímicos y ultraestructurales.

Use of derived adipose stem cells to reduce complications of cutaneous scarring in smokers. An experimental model in rats

Abstract Purpose To evaluate the use of adipose-derived stem cells (ADSC) in reducing the necrosis area in an experimental model of cutaneous ischemic flap in rats submitted to subcutaneous nicotine injection to simulate a smoker patient. Methods In an experimental study, 30 rats were enrolled and divided into two experimental groups of 15 animals all submitted to a subcutaneous nicotine injection to create ischemic cutaneous flaps on their backs. Other 10 animals were used only to obtain adipose tissue derived stem cells (ADSC). The first group (n=15) received ADSC treatment at the end of surgery while the other group, the control (n=15), received no other interventions. After euthanasia, a decal was performed on the whole area of the flap, accurately defining the transition from necrosis to healthy region. Photos of all animals were collected and evaluated by scales standardized by Paint-Autocad- 2015 software to define the area of flap necrosis in each rat. Student T test was performed to compare the groups, considering a p< 0.05 significant. Data were analyzed using SPSS IBM® 18 version. Results Through the analysis of the images by the program Paint-Autocad-2015 and the area of decal obtained by the transparent sheet, we obtained a mean of 46% necrosis of the total area of the flap in the treatment group and 69.4% in the control group. In the descriptive analysis, a mean of 3.7 cm of necrosis CI 95% (3.2 - 4.2) was evident in the treatment group whereas a mean value of 5.56 CI 95% (5.2 - 5.9) was found in control group, with p value <0.001 for this comparison. Conclusion The application of adipose-derived stem cells reduces the percentage of necrosis in an experimental model of randomized cutaneous flap in rats submitted to subcutaneous nicotine injection.

Interferon-gamma-induced local leukocytoclastic vasculitis at the subcutaneous injection site

Abstract Cutaneous reactions associated with interferons (IFNs) treatment are either localized or generalized. The most common presentation of localized reactions at IFNs injection site is usually an erythematous patch or plaque. Local leukocytoclastic vasculitis presenting with cutaneous necrosis is extremely rare. We report a 19-year-old man with hepatitis B who had local leukocytoclastic vasculitis induced by interferon-gama injection at the injection site. After changing the injection sites and using the combined treatment of prednisone and colchicine, the previous lesion healed and no other cutaneous lesion occurred. We also made a mini review of such cases.

Cytotoxicity and genotoxicity of calcium silicate-based cements on an osteoblast lineage

Abstract Several calcium silicate-based biomaterials have been developed in recent years, in addition to Mineral Trioxide Aggregate (MTA). The aim of this study was to evaluate the cytotoxicity, genotoxicity and apoptosis/necrosis in human osteoblast cells (SAOS-2) of pure calcium silicate-based cements (CSC) and modified formulations: modified calcium silicate-based cements (CSCM) and three resin-based calcium silicate cements (CSCR1) (CSCR 2) (CSCR3). The following tests were performed after 24 hours of cement extract exposure: methyl-thiazolyl tetrazolium (MTT), apoptosis/necrosis assay and comet assay. The negative control (CT-) was performed with untreated cells, and the positive control (CT+) used hydrogen peroxide. The data for MTT and apoptosis were submitted to analysis of variance and Bonferroni's posttest (p < 0.05), and the data for the comet assay analysis, to the Kruskal-Wallis and Dunn tests (p < 0.05). The MTT test showed no significant difference among the materials in 2 mg/mL and 10 mg/mL concentrations. CSCR3 showed lower cell viability at 10 mg/mL. Only CSC showed lower cell viability at 50 mg/mL. CSCR1, CSCR2 and CSCR3 showed a higher percentage of initial apoptosis than the control in the apoptosis test, after 24 hours exposure. The same cements showed no genotoxicity in the concentration of 2 mg/mL, with the comet assay. CSC and CSCR2 were also not genotoxic at 10 mg/mL. All experimental materials showed viability with MTT. CSC and CSCR2 presented a better response to apoptosis and genotoxicity evaluation in the 10 mg/mL concentration, and demonstrated a considerable potential for use as reparative materials.

Breast necrosis induced by the use of coumadin: case report and review of literature / Necrose mamária induzida pelo uso de cumarínico: relato de caso e revisão da literatura

The coumadin-induced skin necrosis is rare and occurs more frequently in the breasts, thighs and buttocks. We describe the first case of coumadin necrosis of the breast in Brazil in a 62-year-old patient.

A necrose cutânea induzida por cumarínicos é um evento raro e ocorre com maior frequência nas mamas, coxas e nádegas. Descrevemos o primeiro caso de necrose cumarínica das mamas no Brasil em paciente de 62 anos.

International cooperation Brazil-Cuba-Haiti: the role of community radios in strengthening social mobilization in the public health context in Haiti / Cooperação internacional Brasil-Cuba-Haiti: o papel das rádios comunitárias no fortalecimento da mobilização social no âmbito da saúde pública no Haiti

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.

Propofol or sevoflurane anaesthesia does not affect hepatic integrity as assessed by the M30 & M65 cell death markers & liver enzymes.

Background & objectives: General anaesthetics may induce apoptosis. The pro-apoptotic/necrotic markers M30 (caspase-cleaved cytokeratin-18) and M65 (intact cytokeratin-18) have been used to identify early apoptosis in liver disease. The aim of this study was to detect the effect of propofol and sevoflurane anaesthesia on these markers and blood transaminase levels in female patients undergoing elective surgery. Methods: Sixty-seven women undergoing mastectomy or thyroidectomy under general anaesthesia were randomly allocated to the propofol or sevoflurane groups. Venous blood samples for measuring the apoptotic and necrotic markers M30 and M65 as well as for measuring the alanine aminotransferase (ALT) and the aspartate aminotransferase (AST) liver enzymes were collected before induction of anaesthesia, immediately after completion of surgery, and 24 and 48 h postoperatively. Results. The M30 values preoperatively and 0, 24 and 48 h postoperatively were 280±229, 300±244, 267±198 and 254±189 U/l in the propofol group and 237±95, 242±109, 231±94 and 234±127 U/l in the sevoflurane group, respectively. The M30 values did not differ within or between the groups. The M65 levels at the same time intervals were 470±262, 478±271, 456±339 and 485±273 in the propofol group and 427±226, 481±227, 389±158 and 404±144 U/l in the sevoflurane group, respectively. No significant changes were found in the M65 either within or between the propofol and the sevoflurane groups. The ALT and AST levels did not change at these time intervals. Interpretation & conclusions: Under the present study design propofol or sevoflurane anaesthesia did not induce apoptosis or affected the liver function as assessed by the M30, M65 markers and liver enzymes in patients undergoing mastectomy or thyroidectomy under general anaesthesia.

Severe ischemic bowel necrosis caused by terlipressin during treatment of hepatorenal syndrome

Terlipressin is a vasopressin analogue that is widely used in the treatment of hepatorenal syndrome or variceal bleeding. Because it acts mainly on splanchnic vessels, terlipressin has a lower incidence of severe ischemic complications than does vasopressin. However, it can still lead to serious complications such as myocardial infarction, skin necrosis, or bowel ischemia. Herein we report a case of severe ischemic bowel necrosis in a 46-year-old cirrhotic patient treated with terlipressin. Although the patient received bowel resection, death occurred due to ongoing hypotension and metabolic acidosis. Attention should be paid to patients complaining of abdominal pain during treatment with terlipressin.

Interleukin-10 Down-Regulates Cathepsin B Expression in Fetal Rat Alveolar Type II Cells Exposed to Hyperoxia

PURPOSE: Hyperoxia has the chief biological effect of cell death. We have previously reported that cathepsin B (CB) is related to fetal alveolar type II cell (FATIIC) death and pretreatment of recombinant IL-10 (rIL-10) attenuates type II cell death during 65%-hyperoixa. In this study, we investigated what kinds of changes of CB expression are induced in FATIICs at different concentrations of hyperoxia (65%- and 85%-hyperoxia) and whether pretreatment with rIL-10 reduces the expression of CB in FATIICs during hyperoxia. MATERIALS AND METHODS: Isolated embryonic day 19 fetal rat alveolar type II cells were cultured and exposed to 65%- and 85%-hyperoxia for 12 h and 24 h. Cells in room air were used as controls. Cytotoxicity was assessed by lactate dehydrogenase (LDH) released into the supernatant. Expression of CB was analyzed by fluorescence-based assay upon cell lysis and western blotting, and LDH-release was re-analyzed after preincubation of cathepsin B-inhibitor (CBI). IL-10 production was analyzed by ELISA, and LDH-release was re-assessed after preincubation with rIL-10 and CB expression was re-analyzed by western blotting and real-time PCR. RESULTS: LDH-release and CB expression in FATIICs were enhanced significantly in an oxygen-concentration-dependent manner during hyperoxia, whereas caspase-3 was not activated. Preincubation of FATIICs with CBI significantly reduced LDH-release during hyperoxia. IL-10-release decreased in an oxygen-concentration-dependent fashion, and preincubation of the cells with rIL-10 significantly reduced cellular necrosis and expression of CB in FATIICs which were exposed to 65%- and 85%-hyperoxia. CONCLUSION: Our study suggests that CB is enhanced in an oxygen-concentration-dependent manner, and IL-10 has an inhibitory effect on CB expression in FATIICs during hyperoxia.

Effects of aspirin on mesenteric lymph nodes of rabbits as basis for its use on lymph nodes metastases / Efeitos da aspirina em linfonodos mesentéricos de coelhos como base para o uso em metástases linfonodais

PURPOSE: To evaluate the effects of aspirin 10% and 20% on mesenteric lymph nodes of rabbits as basis for its use on lymph nodes metastases. METHODS: A total of 20 lymph nodes from 20 rabbits (randomized in four groups) were evaluated. Aspirin solutions 10% (groups A and C) and 20% (groups B and D) were injected into mesenteric lymph nodes of healthy rabbits and had its gross and histological effects evaluated at 24 hours (groups A and B) and at seven days (groups C and D). RESULTS: In the groups A and B evaluated at 24 hours it was observed extensive necrosis and hemorrhage, a significant increase in apoptosis throughout the lymph node with medullary sinuses enlargement and an increase in germinal centers. In the groups C and D evaluated at seven days of solution injection there was also an increase in apoptosis with higher elevation of histiocytes and a significant decrease of necrosis and an increase of giant cells was noticed causing a foreign body chronic inflammation. In all comparisons, there were no differences between the concentrations used (10 and 20%). CONCLUSIONS: The injection of aspirin on lymph nodes caused necrosis and an increase of apoptosis after 24 hours and after seven days of treatment there was regeneration of the lymph nodes, with intense decrease of necrosis and a great elevation of apoptosis. These experimental results support future clinical studies on application of aspirin in the treatment of lymphatic metastases, since the increase of apoptosis is one of the pillars of cancer therapy.

OBJETIVO: Avaliar os efeitos do ácido acetilsalicílico a 10% e 20% em linfonodos mesentéricos de coelhos para posterior embasamento e uso em metástases linfonodais. MÉTODOS: Um total de 20 linfonodos de 20 coelhos (divididos aleatoriamente em quatro grupos) foi avaliado. As soluções de aspirina a 10% (grupos A e C) e 20% (grupos B e D) foram injetadas em linfonodos mesentéricos de coelhos sadios e seus efeitos macroscópicos e histológicos foram avaliados em 24 horas (grupos A e B) e em sete dias (grupos C e D). RESULTADOS: Nos grupos avaliados em 24 horas (A e B) foi verificada intensa necrose e hemorragia, aumento importante de apoptose em todo o linfonodo, com alargamento dos seios medulares e aumento dos centros germinativos. Nos grupos avaliados em sete dias (C e D) também houve aumento da apoptose, com maior elevação de histiócitos e diminuição importante da necrose; a hemorragia foi ausente e aumento de células gigantes foi visualizado, conferindo processo inflamatório crônico do tipo corpo estranho. Não houve diferença entre as concentrações utilizadas (10 e 20%) em nenhuma das comparações. CONCLUSÕES: A injeção de aspirina em linfonodos causou necrose e um aumento de apoptose após 24 horas e após sete dias de tratamento, houve regeneração dos gânglios linfáticos, com diminuição intensa de necrose e grande aumento de apoptose. Uma vez que o aumento de apoptose é um dos pilares dos tratamentos antineoplásicos, estes resultados experimentais embasam eventual aplicação clínica da aspirina no tratamento de metástases linfonodais.

Coma blisters after poisoning caused by central nervous system depressants: case report including histopathological findings / Bolhas do coma pós-intoxicação por depressores do sistema nervoso central: relato de caso incluindo achados histopatológicos

Blister formation and eccrine sweat gland necrosis is a cutaneous manifestation associated with states of impaired consciousness, most frequently reported after overdoses of central nervous system depressants, particularly phenobarbital. The case of a 45-year-old woman who developed "coma blisters" at six distinct anatomic sites after confirmed (laboratory) phenobarbital poisoning, associated with other central nervous system depressants (clonazepam, promethazine, oxcarbazepine and quetiapine), is presented. A biopsy from the left thumb blister taken on day 4 revealed focal necrosis of the epidermis and necrosis of sweat gland epithelial cells; direct immunofluorescence was strongly positive for IgG in superficial blood vessel walls but negative for IgM, IgA, C3 and C1q. The patient was discharged on day 21 with no sequelae.

Formação de bolhas e necrose de glândula sudoríparas écrinas é uma manifestação cutânea associada com estados de diminuição da consciência, mais frequentemente relatada após superdosagens de depressores do sistema nervoso central, particularmente fenobabital. Relatamos o caso de uma paciente de 45 anos que desenvolveu "bolhas do coma" após tentativa de suicídio por fenobarbital (confirmada laboratorialmente), associada a outros depressores do sistema nervoso central (clonazepam, prometazina, oxcarbazepina e quetiapina). Biópsia da bolha do 1o quirodáctilo esquerdo no 4o dia de internação revelou necrose focal da epiderme e necrose de células epiteliais de glândula sudorípara; a imunofluorescência direta foi fortemente positiva para IgG na parede superficial dos vasos sanguíneos, mas negativa para IgM, IgA, C3 e C1q. A paciente teve alta no 21o dia, sem seqüelas.

Experimental poisoning by Baccharis megapotamica var. weirii in buffalo / Intoxicação experimental por Baccharis megapotamica var. weirii em búfalos

Five male 6-8 month-old Murrah buffalo calves were orally dosed with the fresh aerial parts of Baccharis megapotamica var. weirii at doses of 1, 3, 4, 5 and 10g/kg body weight (bw) (~1-10mg macrocyclic trichothecenes/kg/bw). The B. megapotamica used for the experiment was harvested on a farm where a recent spontaneous outbreak of poisoning caused by such plant had occurred. Clinical signs appeared 4-20 hours and 4 buffaloes died 18-49 hours after the ingestion of the plant. Clinical signs were apathy, anorexia, and watery diarrhea, fever, colic, drooling, muscle tremors, restlessness, laborious breathing and ruminal atony, and dehydration. The most consistent gross findings were restricted to the gastrointestinal (GI) tract consisted of varying degrees of edema and reddening of the mucosa of the forestomach. Histopathological findings consisted of varying degrees of necrosis of the epithelial lining of the forestomach and of lymphocytes within lymphoid organs and aggregates. Fibrin thrombi were consistently found in sub-mucosal vessels of the forestomach and in the lumen of hepatic sinusoids. It is suggested that dehydration, septicemia and disseminated intravascular coagulation participate in the pathogenesis of the intoxication and play a role as a cause of death. A subsample of B. megapotamica var. weirii was frozen-dried and ground and analyzed using UHPLC (Ultra High Performance Liquid Chromatography) with high resolution Time of Flight mass spectrometry and tandem mass spectrometry, it was shown that the plant material contained at least 51 different macrocyclic trichothecenes at a total level of 1.1-1.2mg/g. About 15-20% of the total trichothecenes contents was found to be monosaccharide conjugates, with two thirds of these being glucose conjugates and one third constituted by six aldopentose conjugates (probably xylose), which has never been reported in the literature.

As partes aéreas verdes de Baccharis megapotamica var. weirii foram administradas oralmente a cinco búfalos da raça Murrah de 6-8 meses de idade nas doses de 1, 3, 4, 5 e 10g/kg de peso corporal (pc) (~1-10mg de tricotecenos macrocíclicos/kg/pc). A planta usada no experimento foi colhida numa fazenda onde um surto recente de intoxicação espontânea por essa planta havia ocorrido. Nos búfalos deste experimento, os sinais clínicos apareceram 4-20 horas e 4 búfalos morreram 18-49 horas após a ingestão da planta. Os sinais clínicos consistiram de apatia, anorexia, diarreia aquosa, febre, cólica, salivação, tremores musculares, inquietação, respiração laboriosa, atonia ruminal e desidratação. Os achados macroscópicos mais consistentes estavam restritos ao trato gastrointestinal (GI) e consistiram de graus variados de edema e avermelhamento da mucosa dos pré-estômagos. Os achados histopatológicos consistiam de vários graus de necrose do epitélio de revestimento dos pré-estômagos e de linfócitos em agregados e órgãos linfoides. Trombos de fibrina foram consistentemente encontrados nos vasos da submucosa dos pré-estômagos e na luz dos sinusoides hepáticos. É sugerido que desidratação, septicemia e coagulação intravascular disseminada participem da patogênese da intoxicação e sejam fatores responsáveis pela morte dos animais afetados pela intoxicação. Uma subamostra de B. megapotamica var. weirii foi congelada a seco, moída e analisada usando UHPLC (Cromatografia Líquida de Ultra Alta Performance) com espectrometria de tempo-de-vôo de alta resolução e espectrometria de massa em tandem. Foi demonstrado que o material de planta analisado continha pelo menos 51 tricotecenos macrocíclicos diferentes num nível total de 1,1-1,2mg/g. Cerca de 15-20% do conteúdo total de tricotecenos eram conjugados de monossacarídeos, sendo dois terços desses, conjugados de glicose e um terço constituídos por seis conjugados de aldopentose (provavelmente xilose), o que nunca tinha sido antes relatado na literatura.

Early administration of peroxisomicine A1 (T-514 extracted from K. parvifolia seeds) causes necrosis of implanted TC-1 cells without affecting target organs in a murine model / La administración temprana de peroxisomicina A1 (T-514 extraída de las semillas de K. parvifolia)causa necrosis de células TC-1 implantadas sin afectar órganos blanco en un modelo murino

Peroxisomicine A1 (PA1), one of the toxins isolated from seeds of plants of the Karwinskia genus, whose targets organs are the liver, kidney, and lungs. There is a selective toxicity in vitro to cancer-cell lines derived from the lungs, liver, and colon, compared to normal cell lines. PA1 caused apoptosis in several cancer-cell lines in culture. In toxic doses to rodents, it causes extensive apoptosis in the liver, kidney, and lungs. In our study we were interested in evaluating, for the first time, the morphological effects of administration of PA1 to implanted TC-1 cells and in the target organs in vivo. The TC-1 cells were cultured and injected into the hind limb of C57BL-6 mice. The animals were divided into 3 groups; those treated with four doses of 1 mg/kg each of PA1, the untreated control, and the vehicle-control groups. All mice were killed 10 days after cell implantation. Samples were obtained from TC-1 cells at the implantation site and from the liver, kidney, and lungs. The samples were processed for examination under light and electron microscopy. In the PA1-treated group, the TC-1 cells had necrosis, whereas in the control groups the tumor cells were undamaged. The target organs did not show any lesions. We demonstrated for the first time that there is a selective toxic effect of PA1 on the TC-1 cells in vivo.

Peroxisomicina A1 (PA1), una de las toxinas aisladas de las semillas de plantas del género Karwinskia, cuyos órganos blanco son hígado, riñón y pulmón. Hay una toxicidad selectiva in vitro contra líneas celulares cancerosas derivadas de pulmón, hígado y colon, comparadas con líneas celulares normales. PA1 causa apoptosis en varias líneas celulares malignas en cultivo. En dosis tóxicas a roedores, causa extensa apoptosis en hígado, riñón y pulmón. En nuestro estudio, estuvimos interesados en evaluar por primera vez los efectos morfológicos de la administración temprana de PA1 sobre células TC-1 implantadas y los órganos blanco in vivo. Las células TC-1 fueron cultivadas e implantadas en la extremidad posterior de ratones C57BL-6. Los animales fueron divididos en tres grupos: tratado con cuatro dosis de 1 mg/kg de peso de PA1, control sin tratamiento y control vehículo. Todos los animales fueron sacrificados 10 días posterior al implante de las células. Se colectaron muestras del sitio del implante de las células TC-1 y de hígado, riñón y pulmón. Las muestras fueron procesadas para su análisis a microscopía de luz y microscopia electrónica de transmisión. En el grupo tratado con PA1, las células TC-1 presentaron necrosis, mientras que en los grupos control las células tumorales se observaron sin daño. Los órganos blanco no mostraron lesión alguna. Demostramos por primera vez que existe un efecto tóxico selectivo de PA1 sobre las células TC-1 in vivo.

Necrosis cutánea por tratamiento anticoagulante oral: caso clínico / Cutaneous necrosis caused by acenocumarol: case report

Cutaneous necrosis is a rare but serious complication, among patients treated with warfarin or acenocumarol derivatives. We report a 71 years old female with a history of deep venous thrombosis, receiving acenocumarol for three months. The treatment was discontinued, but had to be restarted, due to a new episode of thrombosis. Three days after restarting acenocumarol, the patient consulted for ecchymosis and pain of the right foot. At physical examination, there was distal cyanosis and absence of distal pulses. The patient was subjected to an embolectomy with the suspicion of an acute arterial occlusion, but no emboli were found. Due to the possibility of a cutaneous necrosis caused by Acenocumarol, the medication is discontinued. The cutaneous lesions progressed and eight days after the failed embolectomy, a gangrene of the right foot was diagnosed. The patient did not accept amputation dying fourteen days after the first intervention.

A propósito un caso registrado, se resume la historia clínica y se revisa la literatura, dada la escasa frecuencia de esta complicación derivada del tratamiento por anticoagulantes orales. La necrosis cutánea es un evento adverso raro, pero serio, de la anticoagulación con derivados de acenocumarol o warfarina. Se comunicó por primera vez en 1943. La incidencia de la necrosis cutánea inducida por anticoagulantes orales es de 0,01 al 0,1 por ciento de los pacientes tratados. El número de casos publicados en el mundo es de aproximadamente 300, y menos de 100 en lengua inglesa en las últimas tres décadas. Este trabajo reporta el caso de una paciente que presenta necrosis cutánea en hombro izquierdo y pierna derecha.

Trombocitopenia induzida por heparina e necrose cutânea por varfarina: relato de caso / Heparin-induced thrombocytopenia and warfarin-induced skin necrosis: case report

É relatado um caso de trombocitopenia induzida por heparina complicada, com necrose cutânea induzida por varfarina em paciente de 74 anos, sexo feminino, internada com diagnóstico de fratura do colo do fêmur, trombose venosa profunda e tromboembolismo pulmonar. A necrose cutânea induzida por varfarina é uma complicação rara da terapia anticoagulante, com alta morbidade e mortalidade, que pode estar associada à trombocitopenia induzida por heparina.

This paper describes a case of heparin-induced thrombocytopenia complicated by warfarin-induced skin necrosis in a 74-year old female patient hospitalized with diagnoses of a hip fracture, deep vein thrombosis and pulmonary thromboembolism. Warfarin-induced skin necrosis is a rare complication of anticoagulant therapy, with high morbidity and mortality that may be associated with heparin-induced thrombocytopenia.

Gentamicin-induced preconditioning of proximal tubular LLC-PK1 cells stimulates nitric oxide production but not the synthesis of heat shock protein

Nephrotoxicity is the main side effect of antibiotics such as gentamicin. Preconditioning has been reported to protect against injuries as ischemia/reperfusion. The objective of the present study was to determine the effect of preconditioning with gentamicin on LLC-PK1 cells. Preconditioning was induced in LLC-PK1 cells by 24-h exposure to 2.0 mM gentamicin (G/IU). After 4 or 15 days of preconditioning, cells were again exposed to gentamicin (2.0 mM) and compared to untreated control or G/IU cells. Necrosis and apoptosis were assessed by acridine orange and HOESCHT 33346. Nitric oxide (NO) and endothelin-1 were assessed by the Griess method and available kit. Heat shock proteins were analyzed by Western blotting. After 15 days of preconditioning, LLC-PK1 cells exhibited a significant decrease in necrosis (23.5 ± 4.3 to 6.5 ± 0.3%) and apoptosis (23.5 ± 4.3 to 6.5 ± 2.1%) and an increase in cell proliferation compared to G/IU. NO (0.177 ± 0.05 to 0.368 ± 0.073 ìg/mg protein) and endothelin-1 (1.88 ± 0.47 to 2.75 ± 0.53 pg/mL) production significantly increased after 15 days of preconditioning compared toG/IU. No difference in inducible HSP 70, constitutive HSC 70 or HSP 90 synthesis in tubular cells was observed afterpreconditioning with gentamicin. The present data suggest that preconditioning with gentamicin has protective effects on proximal tubular cells, that involved NO synthesis but not reduction of endothelin-1 or production of HSP 70, HSC 70, or HSP 90. We conclude that preconditioning could be a useful tool to prevent the nephrotoxicity induced by gentamicin.

Colonic Mucosal Necrosis Following Administration of Calcium Polystryrene Sulfonate (Kalimate) in a Uremic Patient

Colonic necrosis is known as a rare complication following the administration of Kayexalate (sodium polystryrene sulfonate) in sorbitol. We report a rare case of colonic mucosal necrosis following Kalimate (calcium polystryrene sulfonate), an analogue of Kayexalate without sorbitol in a 34-yr-old man. He had a history of hypertension and uremia. During the management of intracranial hemorrhage, hyperkalemia developed. Kalimate was administered orally and as an enema suspended in 20% dextrose water to treat hyperkalemia. Two days after administration of Kalimate enema, he had profuse hematochezia, and a sigmoidoscopy showed diffuse colonic mucosal necrosis in the rectum and sigmoid colon. Microscopic examination of random colonic biopsies by two consecutive sigmoidoscopies revealed angulated crystals with a characteristic crystalline mosaic pattern on the ulcerated mucosa, which were consistent with Kayexalate crystals. Hematochezia subsided with conservative treatment after a discontinuance of Kalimate administration.