Stabilin receptors clear LPS and control systemic inflammation.

Lipopolysaccharides (LPSs) cause lethal endotoxemia if not rapidly cleared from blood circulation. Liver sinusoidal endothelial cells (LSEC) systemically clear LPS by unknown mechanisms. We discovered that LPS clearance through LSEC involves endocytosis and lysosomal inactivation via Stabilin-1 and 2 (Stab1 and Stab2) but does not involve TLR4. Cytokine production was inversely related to clearance/endocytosis of LPS by LSEC. When exposed to LPS, Stabilin double knockout mice (Stab DK) and Stab1 KO, but not Stab2 KO, showed significantly enhanced systemic inflammatory cytokine production and early death compared with WT mice. Stab1 KO is not significantly different from Stab DK in circulatory LPS clearance, LPS uptake and endocytosis by LSEC, and cytokine production. These data indicate that (1) Stab1 receptor primarily facilitates the proactive clearance of LPS and limits TLR4-mediated inflammation and (2) TLR4 and Stab1 are functionally opposing LPS receptors. These findings suggest that endotoxemia can be controlled by optimizing LPS clearance by Stab1.

A Panel of Protein Kinase Chemosensors Distinguishes Different Types of Fatty Liver Disease.

The worldwide incidence of fatty liver disease continues to rise, which may account for concurrent increases in the frequencies of more aggressive liver ailments. Given the existence of histologically identical fatty liver disease subtypes, there is a critical need for the identification of methods that can classify disease and potentially predict progression. Herein, we show that a panel of protein kinase chemosensors can distinguish fatty liver disease subtypes. These direct activity measurements highlight distinct differences between histologically identical fatty liver diseases arising from diets rich in fat versus alcohol and identify a previously unreported decrease in p38α activity associated with a high-fat diet. In addition, we have profiled kinase activities in both benign (diet-induced) and progressive (STAM) disease models. These experiments provide temporal insights into kinase activity during disease development and progression. Altogether, this work provides the basis for the future development of clinical diagnostics and potential treatment strategies.

Ligand Binding and Signaling of HARE/Stabilin-2.

The Stabilin receptors are a two-member family in the type H class of scavenger receptors. These dynamic receptors bind and internalize multiple ligands from the cell surface for the purpose of clearing extracellular material including some synthetic drugs and for sensing the external environment of the cell. Stabilin-1 was the first receptor to be cloned, though the biological activity of Hyaluronic Acid Receptor for Endocytosis (HARE)/Stabilin-2 was observed about 10 years prior to the cloning of Stabilin-1. Stabilin-1 has a more diverse expression profile among the tissues than HARE/Stabilin-2. This review will focus on HARE/Stabilin-2 and its interactions with hyaluronan, heparin, and phosphorothioate antisense oligonucleotides and what is known about how this receptor participates in signaling upon ligand binding.

Purification of Hepatocytes and Sinusoidal Endothelial Cells from Mouse Liver Perfusion.

This protocol demonstrates a method for obtaining high yield and viability for mouse hepatocytes and sinusoidal endothelial cells (SECs) suitable for culturing or for obtaining cell lysates. In this protocol, the portal vein is used as the site for catheterization, rather than the vena cava, as this limits contamination of other possible cell types in the final liver preparation. No special instrumentation is required throughout the procedure. A water bath is used as a source of heat to maintain the temperature of all the buffers and solutions. A standard peristaltic pump is used to drive the fluid, and a refrigerated table-top centrifuge is required for the centrifugation procedures. The only limitation of this technique is the placement of the catheter within the portal vein, which is challenging on some of the mice in the 18 - 25 g size range. An advantage of this technique is that only one vein is utilized for the perfusion and the access to the vein is quick, which minimizes ischemia and reperfusion of the liver that reduces hepatic cell viability. Another advantage to this protocol is that it is easy to distinguish live from dead hepatocytes by eyesight due to the difference in cellular density during the centrifugation steps. Cells from this protocol may be used in cell culture for any downstream application as well as processed for any biochemical assessment.

Oxidative injury in V79 Chinese hamster cells: protective role of the superoxide dismutase mimetic MnTM-4-PyP.

Oxidative cell injury could be induced by different reactive oxygen species (ROS) operating in multiple pathways. The present work is focused on three different models of oxidative stress: the xanthine/xanthine oxidase system (XXO), an extracellular superoxide anion generator; tert-butylhydroperoxide (TBHP), an analogue of lipid hydroperoxides; and doxorubicin (Dox), an anticancer drug. Superoxide and peroxyl radicals, among other ROS, could be effectively scavenged by MnTM-4-PyP, a polyfunctional catalytic antioxidant. In this report, we have addressed the role of MnTM-4-PyP on the protection against the cytotoxicity induced by the three aforementioned oxidants. The effect of MnTM-4-PyP (0.1-100 microM) was evaluated in V79 fibroblasts using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide reduction and the crystal violet assays, as well as the mitotic index. Also, the generation of intracellular ROS was studied by the fluorescent probe dihydroethidium. MnTM-4-PyP has shown significant protective effects against the cytotoxicity of XXO and TBHP, increasing the cell viability in approximately 40% and reducing the intracellular level of ROS. However, no considerable protection occurred against Dox. The three oxidants caused a mitotic index reduction that was not altered by MnTM-4-PyP. In summary, MnTM-4-PyP appears to be a promising agent for the protection against oxidative injury. However, it has shown differential responses, reinforcing the need to study different experimental models for the adequate evaluation of its potentialities as a catalytic antioxidant.

Paraneoplastic necrotizing myopathy in a woman with breast cancer: a case report.

INTRODUCTION: Paraneoplastic necrotizing myopathy is a rare disorder, described as a proximal, symmetrical, and rapidly progressing myopathy that is manifested as a paraneoplastic syndrome. Diagnosis is established via histological examination of the muscle biopsy. CASE PRESENTATION: We present the case of a 53-year-old woman, born in Guinea-Bissau, with a history of locally advanced breast cancer, diagnosed ten months previously. The patient had experienced a progressively proximal muscle weakness of the lower extremities, which led to a total inability to walk. Upon neurological examination, the patient showed muscle weakness and atrophy in both proximal lower extremities without myalgia. Muscle strength was graded according to the Medical Research Council Scale as 2 out of 5 in the bilateral iliopsoas muscle, and 4 out of 5 in the bilateral quadriceps femoris. The deep-tendon reflexes were hypoactive. The laboratory examination showed increased values of serum creatinine kinase and myoglobin. An electromyogram showed an incomplete interference pattern during voluntary contraction in the iliopsoas and quadriceps femoris. The motor nerve conduction was 44.1 m/s and 44.3 m/s in the right and left tibial nerves, respectively, and 46.5 m/s and 46.1 m/s in the right and left peroneal nerves, respectively. The sensory motor nerve conductions and the compound motor action potential amplitudes were normal. These findings, despite not being specific, suggested a myopathy. Consequently, a muscle biopsy was performed. A biopsy specimen showed myopathic changes that were characteristic of a necrotizing myopathy. CONCLUSION: Treatment for this syndrome consists of controlling the tumor, and providing corticoid therapy. This led to the partial remission of the neurological manifestations.

Occurrence of yeasts, enterococci and other enteric bacteria in subgingival biofilm of HIV-positive patients with chronic gingivitis and necrotizing periodontitis / Ocorrência de leveduras, enterococos e outras bactérias entéricas no biofilme subgengival de pacientes HIV-positivos com gengivite crônica e periodontite necrosante

The purpose of this study was to determine the prevalence of enteric bacteria and yeasts in biofilm of 80 HIV-positive patients with plaque-associated gingivitis or necrotizing periodontitis. Patients were subjected to extra, intra oral and radiographic examinations. The oral hygiene, bleeding on probing, gingival conditions, and attachment loss were evaluated. Clinical specimens were collected from gingival crevices or periodontal pockets, transferred to VMGA III, diluted and transferred to Sabouraud Dextrose agar with 100 µg/ml of chloramphenicol, peptone water, EVA broth, EMB agar, SS agar, Bile esculin agar and Brilliant green agar. Isolation of yeasts was carried out at room temperature, for 3-7 days; and for the isolation of enteric microorganisms plates were incubated at 37ºC, for 24-48 h. The yeasts identification was performed according to the carbon and nitrogen assimilation, fermentation of carbohydrates and germ tube formation. Bacteria were identified according to their colonial and cellular morphologies and biochemical tests. Yeasts were identified as Candida albicans and its occurrence was more common in patients with CD4+ below 200/mm³ and was affected by the extension of periodontal involvement (P = 0.0345). Enteric bacteria recovered from clinical specimens were identified as Enterobacter sakazakii, Enterobacter cloacae, Serratia liquefaciens, Klebsiella oxytoca and Enterococcus sp. Enterobacteriaceae and enterococci were detected in 32.5 percent of clinical samples from patients with necrotizing periodontitis. In conclusion, non-oral pathogenic bacteria and C. albicans were more prevalent in periodontal sites of HIV-positive patients with necrotizing periodontitis and chronic gingivitis.

O objetivo desse estudo foi avaliar a ocorrência de bactérias entéricas e leveduras no biofilme subgengival de pacientes HIV-positivos com gengivite crônica ou periodontite necrosante. Os pacientes foram submetidos a exame clínico e radiográfico e de higiene bucal, sangramento à sondagem, condições gengivais e a perda de inserção. Os espécimes clínicos de sulcos gengivais ou bolsas periodontais foram inoculados em ágar Sabouraud dextrose com 100 mg/ml de cloranfenicol, água peptonada, caldo EVA, ágar EMB, ágar SS, ágar Bile esculina e ágar verde brilhante. O cultivo de leveduras foi realizado à temperatura ambiente, de 3-7 dias; das enterobactérias a 37ºC de 24-48 h. A identificação das leveduras foi realizada pela assimilação de carbono e nitrogênio, fermentação de açucares e formação de tubo germinativo. As bactérias de acordo com a morfologia celular e colonial e testes bioquímicos. Foram identificadas Candida albicans e sua prevalência foi maior em pacientes com contagens de CD4+ < 200/mm³, e sua ocorrência foi afetada pela extensão da destruição periodontal (P = 0,0345). Enterobacteriaceae e enterococos foram detectados em 32,5 por cento dos pacientes com periodontite necrosante. As enterobactérias foram Enterobacter sakazakii, E. cloacae, Serratia liquefaciens, Klebsiella oxytoca e Enterococcus sp. Concluiu-se que bactérias patogênicas exógenas à cavidade bucal e C. albicans podem ser detectadas no biofilme subgengival de pacientes HIV-positivos com periodontite necrosante e gengivite.

Occurrence of yeasts, enterococci and other enteric bacteria in subgingival biofilm of HIV-positive patients with chronic gingivitis and necrotizing periodontitis.

The purpose of this study was to determine the prevalence of enteric bacteria and yeasts in biofilm of 80 HIV-positive patients with plaque-associated gingivitis or necrotizing periodontitis. Patients were subjected to extra, intra oral and radiographic examinations. The oral hygiene, bleeding on probing, gingival conditions, and attachment loss were evaluated. Clinical specimens were collected from gingival crevices or periodontal pockets, transferred to VMGA III, diluted and transferred to Sabouraud Dextrose agar with 100 µg/ml of chloramphenicol, peptone water, EVA broth, EMB agar, SS agar, Bile esculin agar and Brilliant green agar. Isolation of yeasts was carried out at room temperature, for 3-7 days; and for the isolation of enteric microorganisms plates were incubated at 37°C, for 24-48 h. The yeasts identification was performed according to the carbon and nitrogen assimilation, fermentation of carbohydrates and germ tube formation. Bacteria were identified according to their colonial and cellular morphologies and biochemical tests. Yeasts were identified as Candida albicans and its occurrence was more common in patients with CD4+ below 200/mm(3) and was affected by the extension of periodontal involvement (P = 0.0345). Enteric bacteria recovered from clinical specimens were identified as Enterobacter sakazakii, Enterobacter cloacae, Serratia liquefaciens, Klebsiella oxytoca and Enterococcus sp. Enterobacteriaceae and enterococci were detected in 32.5% of clinical samples from patients with necrotizing periodontitis. In conclusion, non-oral pathogenic bacteria and C. albicans were more prevalent in periodontal sites of HIV-positive patients with necrotizing periodontitis and chronic gingivitis.

[Lung cancer and cutaneous metastasis]. / Cancro do pulmão e metastases cutâneas.

The authors did a review of patients with lung neoplasms and cutaneous metatization diagnosed in the period from 1999 to 2004 and followed in the Pneumologic Oncologic department of the Hospital Sousa Martins (H SM). We have analysed the following variables: sex, race, hystologic diagnosis, clinical stage, therapeutics, impact of the appearance of cutaneous metastization and survival time. Five of the 114 patients with lung neoplasms (4.3%), presented with cutaneous metastization, two males and three females with an average age of 69 years. In one of the patients the cutaneous lesions were synchronic, and in the others were metachronic. The most prevalent histologic type was the adenocarcinoma. The average survival time after the cutaneous metastization was 3.8 months. The results are compared with others present in the world literature.

A relação entre assimetria das arcadas dentárias e traumatismos faciais / Relationship between asymetry of the dental archs and facial trauma

Com o objetivo de estudar a relação entre a assimetria das arcadas dentárias e traumatismo faciais, foi investigada a história de trauma em 230 indivíduos portadores de maloclusões de classe I,II e III de Angle. Os resultados não revelaram uma associação estatisticamente significante entre estes dois fatores. Porém, dentre as maloclusões assimétricas de Angle, a que apresentou maior número de casos de trauma foi a classe III

Os tipos faciais e as maloclusões de Angle / Facial types and Angle's malocclusions

A face humana apresenta três tipos morfológicos: dolicocéfalo, braquicéfalo e mesocéfalo. O próposito desta pesquisa foi avaliar, numa amostra de 230 indivíduos a relação do tipo facial com as maloclusões de Angle. Embora não tenha sido estatisticamente significante, observou-se que na classe I predominou o tipo mesocéfalo e na classe III uma leve predominância do tipo dolicocéfalo

Prevalência de microrganismos periodontopatogênicos e superinfectantes em pacientes HIV-positivos assintomáticos e sintomáticos portadores de gengivites e periodontites / The prevalence of periodontalpathogenic and opportunistic microorganisms in asymptomatic and symptomatic HIV seropositive patients with gingivitis and periodontitis

Foram examinados 402 pacientes portadores do Vírus da Imunodeficiência Humana (HIV), dos quais selecionaram-se os primeiros 80 que se enquadravam nos critérios pré-estabelecidos para esta pesquisa. Os pacientes estudados apresentavam faixa etária entre 20 e 43 anos (idade média de 31,5), eram de ambos os sexos (59 homens e 21 mulheres) e traziam um relatório médico descritivo sobre a última contagem, em valores absolutos, de linfócitos T CD4 positivos (CD4+). Aqueles que apresentavam o valor do CD4+ >= 200 células/mm(3) de sangue (CD4 >= 200) foram considerados HIV-positivos assintomáticos e aqueles com CD4 < 200, HIV-positivos sintomáticos ou portadores da AIDS. Todas as normas de segurança relacionadas à proteçäo do profissional e dos pacientes foram rigorosamente obedecidas...

Tratamento periodontal integrado de um caso clínico de síndrome de Papillon-Lefèvre / The integrated periodontal treatment in Papillo-Lefèvre syndrome clinic case

Foi realizado tratamento periodontal integrado em uma adolescente de 12 anos de idade, portadora da Síndrome de Papillo-Lefèvre, a qual é caracterizada por hiperqueratose das palmas das mãos e planta dos pés, além de periodontite de estabelecimento precoce e rápida progressão que leva à perda prematura dos dentes decíduos e permanentes. Após os exames clínico, radiográfico, microbiológico e imunológico, que confirmaram o diagnóstico definitivo, foram realizadas as exodontias dos dentes condenados, seguidas do tratamento periodontal composto pela motivação quanto a uma técnica adequada de higiene bucal e raspagem, aplainamento, alisamento e polimento dos dentes remanescentes, com antibioticoterapia complementar. Diante dos resultados clínicos e microbiológicos bastantes satisfatórios, observados na fase de controle e manutenção periódicos, procedeu-se a reabilitação bucal que devolveu o equilíbrio oclusal necessário para o desenvolvimento e funcionamento adequado do aparelho estomatognático, bem como integrou a paciente física e psicologicamente no seu meio social