Distinct Regulation of Host Responses by ERK and JNK MAP Kinases in Swine Macrophages Infected with Pandemic (H1N1) 2009 Influenza Virus

Swine influenza is an acute respiratory disease in pigs caused by swine influenza virus (SIV). Highly virulent SIV strains cause mortality of up to 10%. Importantly, pigs have long been considered “mixing vessels” that generate novel influenza viruses with pandemic potential, a constant threat to public health. Since its emergence in 2009 and subsequent pandemic spread, the pandemic (H1N1) 2009 (H1N1pdm) has been detected in pig farms, creating the risk of generating new reassortants and their possible infection of humans. Pathogenesis in SIV or H1N1pdm-infected pigs remains poorly characterized. Proinflammatory and antiviral cytokine responses are considered correlated with the intensity of clinical signs, and swine macrophages are found to be indispensible in effective clearance of SIV from pig lungs. In this study, we report a unique pattern of cytokine responses in swine macrophages infected with H1N1pdm. The roles of mitogen-activated protein (MAP) kinases in the regulation of the host responses were examined. We found that proinflammatory cytokines IL-6, IL-8, IL-10, and TNF-α were significantly induced and their induction was ERK1/2-dependent. IFN-β and IFN-inducible antiviral Mx and 2′5′-OAS were sharply induced, but the inductions were effectively abolished when ERK1/2 was inhibited. Induction of CCL5 (RANTES) was completely inhibited by inhibitors of ERK1/2 and JNK1/2, which appeared also to regulate FasL and TNF-α, critical for apoptosis in pig macrophages. We found that NFκB was activated in H1N1pdm-infected cells, but the activation was suppressed when ERK1/2 was inhibited, indicating there is cross-talk between MAP kinase and NFκB responses in pig macrophages. Our data suggest that MAP kinase may activate NFκB through the induction of RIG-1, which leads to the induction of IFN-β in swine macrophages. Understanding host responses and their underlying mechanisms may help identify venues for effective control of SIV and assist in prevention of future influenza pandemics

[Polysaccharide Amylopectin-like Storage Myopathy]

We report a late onset form of polysaccharide myopathy with progressive limb girdle muscles weakness, without cardiomyopathy. Muscle biopsy showed a vacuolar myopathy in type 1 fibres. The PAS positive diastase resistant deposits were made of filamentous material at electron microscopy similar to long chain glyogen. Muscle glycogen levels and glycogen metabolism enzymes were normal. Numerous abnormal mitochondrial with paracrystalline inclusions were observed around the storage material. Twelve patients with polysaccharide amylopectin-like storage myopathy have previously been reported. This disease must be distinguished from other diseases with polysaccharide accumulation such as branching enzyme deficiency and some cases of phosphofructokinase deficiency. In other disorders, no deficient enzymes in the glycogen pathway was found. Some of them show systemic storage (Lafora disease, adult polyglucosan body disease). Corpora amylacea, Bielchowsky bodies and basophilic degeneration of the myocardium represent localised depositions. A few inclusions can also be observed in hypothyroid myopathy. In polysaccharide myopathy allosteric inactivation of phosphofructokinase by a mitochondrial dysfunction is considered by analogy with cases of polysaccharide storage related to phosphofructokinase deficiency

Esofagites em pacientes com síndrome de imunodeficiência adquirida: estudo histológico e imunoistoquímico Esophagitis in patients with acquired human immunodeficiency syndrome: an histological and immunohistochemistry study

RACIONAL: A maioria dos pacientes com síndrome da imunodeficiência adquirida cursa com sintomas gastrointestinais ao longo da sua evolução. A alta prevalência e morbidade das esofagites nesses pacientes são amplamente reconhecidas. OBJETIVOS: Graduar, histologicamente, as esofagites; identificar os agentes associados, tais como Candida sp, citomegalovírus, herpes vírus e micobactérias; identificar, através da imunoistoquímica, os seguintes agentes: citomegalovírus, herpes vírus I e II, vírus Epstein-Barr, vírus do papiloma humano e vírus da imunodeficiência adquirida; verificar a contribuição da imunoistoquímica para o diagnóstico dos agentes infecciosos; verificar a associação entre os achados histológicos e endoscópicos; verificar a relevância do número de fragmentos na caracterização dos agentes etiológicos. MÉTODOS: Estudaram-se, retrospectivamente, biopsias esofagianas em 227 pacientes com síndrome da imunodeficiência adquirida. Utilizaram-se as colorações de hematoxilina e eosina, PAS ("periodic acid of Schiff"), prata de Grocott e Ziehl-Nielsen, assim como a imunoistoquímica para a detecção de infecções por agentes oportunistas. Aspectos endoscópicos também foram avaliados. RESULTADOS: A esofagite inespecífica acentuada, localizada no terço inferior, foi o tipo mais freqüente. A Candida sp foi o agente mais encontrado, seguida de citomegalovírus, herpes vírus e micobactérias. A presença de placa e ulceração sugeriu o diagnóstico de candidíase e esofagite por citomegalovírus, respectivamente. O herpes vírus I não foi encontrado isolado e sim associado ao herpes vírus II. Não houve imunorreatividade para o vírus Epstein-Barr e o vírus da imunodeficiência adquirida. O número de fragmentos nas amostras não influenciou na detecção do agente etiológico. CONCLUSÃO: Os achados endoscópicos de lesão em placa ou de úlcera estão associados com os diagnósticos de Candida sp e citomegalovírus, respectivamente. O emprego da técnica de imunoistoquímica auxilia no diagnóstico das esofagites virais e torna possível detectar o citomegalovírus em esôfagos normais à endoscopia e/ou ao exame histopatológico.<br>BACKGROUND: Almost all patients with acquired immunodeficiency virus syndrome will have gastrointestinal symptoms during the course of their illness. The high prevalence and complications of esophagitis are well documented. AIM: Graduate esophagitis; identify microorganisms like Candida sp, cytomegalovirus, herpesvirus and mycobacteria; identify by immunohistochemical staining viral agents cytomegalovirus, herpesvirus I, herpesvirus II, Epstein-Barr Virus, human papilloma virus and human immunodeficiency virus; verify how immunohistochemistry changes the profile of esophagitis; verify the association between the histological and endoscopical findings; verify the relevance of the number of fragments studied in the characterization of the histological agents. METHODS: We studied retrospectively esophageal biopsies in 227 patients with acquired immunodeficiency virus syndrome using hematoxylin and eosin, PAS (periodic acid of Schiff), Groccott and Ziehl-Nielsen stains and immunoperoxidase stains to detect opportunistic agents. Endoscopic aspects were studied. RESULTS: The non-specific esophagitis grade III, in the inferior third of the esophagus, was the most frequent type. Candida sp was the most frequent agent, followed by viruses cytomegalovirus, herpesvirus and mycobacteria. The presence of plaque and ulceration suggested the diagnosis of esophageal candidiasis and cytomegalovirus esophagitis. Immunohistochemical allowed the characterization of cytomegalovirus and of herpesvirus in those cases where other techniques could not achieve it, furthermore the cytomegalovirus was also found in histological normal cases, making the use of this technique advisable in routine diagnosis. The herpesvirus I was not found isolated but associated to herpesvirus II. We have not found immunoreactivity for the Epstein-Barr virus and the human immunodeficiency virus. The number of fragments does not seem to influence the detection of the etiologic agent. CONCLUSION: The endoscopic findings of plaques or ulcers are associated with candidiasis or cytomegalovirus esophagitis. Immunohistochemisty improved the diagnosis of viral infections. It is possible to detect cytomegalovirus infections in endoscopic and histologic normal cases