Alterações vasculares na coróide de ratos diabéticos tratados e não tratados

OBJETIVO: Conhecer os efeitos do diabetes e o impacto de seu tratamento medicamentoso em curto e longo prazo sobre os vasos da coróide e membrana de Bruch. MÉTODOS: Foram estudados 30 ratos Wistar, divididos em 3 grupos experimentais: grupo controle (GC), grupo diabético (GD) e grupo diabético tratado (GT), estudados 1 mês (momento M1) e 12 meses (momento M2) após o início do experimento. O diabetes foi induzido por aloxana endovenosa, na dose de 42 mg/kg. O GT foi tratado com hipoglicemiante oral (acarbose) e insulina subcutânea. Após o sacrifício, os olhos foram preparados para exame ao microscópio eletrônico de transmissão, interessando a ultra-estrutura da membrana de Bruch e os vasos da coróide. RESULTADOS: O exame ultra-estrutural da coróide dos ratos diabéticos mostrou depósitos na membrana de Bruch, acúmulo de vesículas, glicogênio e corpos densos no citoplasma das células endoteliais. O grupo mais afetado foi de ratos diabéticos de 12 meses (GDM2). Os animais com menor intensidade de alterações foram os ratos tratados por 12 meses (GTM2). CONCLUSÃO: Os ratos diabéticos desenvolveram alterações degenerativas na membrana de Bruch e vasos da coróide. Estas alterações foram mais evidentes nos animais submetidos à doença crônica, mas também ocorreram agudamente. O tratamento a curto prazo não foi capaz de evitar os processos degenerativos. A longo prazo, o tratamento inibiu a progressão destes processos.

Linfonodo pulmonar na paracoccidioidomicose aguda infantil (relato de um caso).

The primary complex like Ghon was observed in a child's clinical roentgenographic study. C.S., white, male, 6 years old, was born in Curitiba (PR), Brazil and living in Guaratingueta (SP), Brazil, developed common cold, bimodal diary fever, chills, shake and sweats. Dyspnea, cough with general lymphadenopathy. Foot and right shoulder arthralgias. Six months ago visited a cave, equitation practice, dog and cat contacts and no transfusion, frontal sweats, fever (38.4 degrees C). T.A. was 8/6, tachycardia in generalized lymphadenopathy. Cardiopulmonary system was normal, mesogastric tumoral mass, hepatosplenomegaly and no ascites. Bone marrow with eosinophilia; nodule demonstrated presence of P. brasiliensis, hypoalbuminemia; hyperglobulinemia; anemia; leukocytosis with eosinophilia. Immunodiffusion with exoantigen 43 kd of P. brasiliensis was 1/32. Primary complex like Ghon was observed in interstitial pneumonia followed by mediastinal and mesogastric mass (35 to 40 days). Clavicular osteolytic lesions (45 to 60 days) appeared during paracoccidioidomycosis therapy. Recovery was observed 2 months after treatment of acute infantile paracoccidioidomycosis.

IgG, IgM and IgA antibody response for the diagnosis and follow-up of paracoccidioidomycosis: Comparison of counterimmunoelectrophoresis and complement fixation

IgG, IgM and IgA antibodies to GP43 (glycoprotein fraction of Paracoccidioides brasiliensis) were measured by ELISA in 63 samples from 23 patients with paracoccidioidomycosis before and twice after chemotherapy was started. Antibodies against P. brasiliensis were detected by indirect immunofluorescence (IF) (IgG, IgM and IgA isotypes), counterimmunoelectrophoresis (CIE) and complement fixation. Two control groups composed of 19 healthy individuals and 12 patients with other diseases (six with histoplasmosis, three with tuberculosis and three with other mycoses). The highest efficiency percentages were found with IgG and IgA- ELISA (100%), IgG-IF (96.2%), CIE (94.4%) and the lowest with CF (75.9%). Highest positive and negative predictive values (100%) were observed for IgG and IgA ELISA. IgG and IgM-ELISA antibodies are more often found in patients with acute than chronic disease (P = 0.01). Four to six months after treatment follow-up showed decreased levels of IgG and IgM-ELISA for acute cases and decreased titres of CIE for chronic cases in relation to pretreatment levels. This study suggests that IgG-ELISA anti-GP43 represents a good marker to monitor clinical response to therapy.

Edema agudo pulmonar associado à obstrução das vias aéreas. Relato de caso

BAKGROUND AND OBJECTIVES: Negative pressure pulmonary edema has been defined as non-cardiogenic edema, with transudation of fluid to the interstitial space of the lungs due to an increase in negative intrathoracic pressure secondary to obstruction of the upper airways. This is the case of a healthy patient who underwent general anesthesia and developed acute pulmonary edema after extubation. CASE REPORT: A 23-year old female patient, physical status ASA II, underwent gynecologic videolaparoscopy under general anesthesia. The procedure lasted 3 hours without intercurrence. After extubation the patient developed laryngeal spasm and reduction in oxygen saturation. The patient improved after placement of an oral cannula and administration of oxygen under positive pressure with a face mask. Once the patient was stable she was transferred to the recovery room where, shortly after her arrival, she developed acute pulmonary edema with elimination of bloody serous secretion. Treatment consisted of elevation of the head, administration of oxygen via a face mask, furosemide and fluid restriction. Chest X-ray was compatible with acute pulmonary edema and normal cardiac area. Electrocardiogram (ECG), echocardiogram and cardiac enzymes were normal. The condition of the patient improved and she was discharged from the hospital the following day, asymptomatic. CONCLUSIONS: Acute pulmonary edema associated with obstruction of the upper airways can aggravate surgical procedures with low morbidity, affecting mainly young patients. Early treatment should be instituted because it has a fast evolution and, in most cases, resolves without lasting damages. © Sociedade Brasileira de Anestesiologia, 2008.

Intestinal anti-inflammatory activity of coumarin and 4-hydroxycoumarin in the trinitrobenzenesulphonic acid model of rat colitis

Coumarins represent an important class of phenolic compounds with multiple biological activities, including inhibition of lipidic peroxidation and neutrophil-dependent anion superoxide generation, anti-inflammatory and immunosuppressor actions. All of these proprieties are essential for that a drug may be used in the treatment of inflammatory bowel disease. The present study examined intestinal anti-inflammatory activity of coumarin and its derivative, the 4-hydroxycoumarin on experimental ulcerative colitis in rats. This was performed in two different experimental settings, i.e. when the colonic mucosa is intact or when the mucosa is in process of recovery after an initial insult. The results obtained revealed that the coumarin and 4-hydroxycoumarin, at doses of 5 and 25 mg/kg, significantly attenuated the colonic damage induced by trinitrobenzenesulphonic acid (TNBS) in both situations, as evidenced macroscopically, microscopically and biochemically. This effect was related to an improvement in the colonic oxidative status, since coumarin and 4-hydroxycoumarin prevented the glutathione depletion that occurred as a consequence of the colonic inflammation. © 2008 Pharmaceutical Society of Japan.

Edema agudo de pulmão de pressão negativa como complicação grave de síndrome de apneia obstrutiva do sono em crianças. Relatos de casos

Introduction: Obstructive sleep apnea syndrome is related to cardiopulmonary complications in children. It is important to know its patophysiology and possible complications to help reduce risks in this group. Aims: To report three cases of severe cardiorespiratory complications of obstructive sleep apnea managed in the intensive care unit (ICU). Case report: Two children with no previous diagnosis of obstructive sleep apnea syndrome suffered acute congestive heart failure and acute lung oedema with need of ICU and improved after adenotonsillectomy. In a third case, the patient had acute lung oedema as a complication after adenotonsillectomy. Conclusions: Paediatricians and otolaryngologists must be aware of the clinical manifestations of severe sleep apnea. Early referring to treatment and special attention at pre and post surgical periods are essentials to avoid serious complications.

Previous infection with Staphylococcus aureus strains attenuated experimental encephalomyelitis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Trichodina heterodentata (Ciliophora) infestation on Prochilodus lineatus larvae: a host-parasite relationship study

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Studies of natural killer cells in patients with paracoccidioidomycosis

The number and activity of natural killer (NK) cells were studied in 34 untreated patients with paracoccidioidomycosis, 20 with the chronic form of the disease and 14 with the acute form. NK cells were detected with monoclonal antibody Leu-11c and the cytotoxic activity was measured using a single cell assay against K562 target cells. Both groups of patients had an increased number of circulating NK cells, their cytotoxic activity being significantly lower than in the healthy controls. These findings may be of importance in the immunological disturbances associated with paracoccidioidomycosis since NK cells exert important immune effector functions and may play a role in resistance against Paracoccidioides brasiliensis.

Efeito prolilático da associaçao de MOG com vitamina D na encefalomielite autoimune experimental

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Sorveglianza dell’infezione da virus dell’epatite E (HEV) in Italia: from farm to table

L'epatite E è una malattia umana con caratteristiche di epatite acuta, causata da un ssRNA virus (HEV). Nel 1997, HEV è stato identificato per la prima volta nei suini (SwHEV). In seguito, diverse evidenze, tra cui la vicinanza genetica tra ceppi umani e suini, suggerirono la trasmissione zoonotica del virus. Nella presente tesi, l’identificazione di SwHEV è stata condotta mediante ricerca di porzioni di genoma virale attraverso RT-PCR. Dal 2011 al 2013, sono stati analizzati 343 campioni fecali (da 19 allevamenti) e 70 bili (da 2 macelli) prelevati da altrettanti suini, in diverse Regioni italiane. E’ stato inoltre condotto uno studio retrospettivo su 78 feci (da 3 allevamenti) raccolte nel 2000. Il virus è stato identificato nel 24,5% e 19,2% delle feci raccolte rispettivamente nel 2011-2013 e nel 2000. Nessuna bile è risultata positiva. Mediante sequenziamento del genoma intero di uno dei virus identificati, è stata condotta l’analisi filogenetica per valutarne il grado di correlazione con alti ceppi suini e umani. La presenza di HEV è stata valutata lungo la filiera di produzione suina, dal macello al punto vendita. Trentaquattro campioni di feci, fegato e muscolo sono stati raccolti in un macello da altrettanti suini sani (età:6-7 mesi). Quattordici feci e 2 fegati, sono risultati positivi per HEV. Sono state prelevate 129 salsicce sia allo stabilimento di trasformazione sia alla vendita, ma nessuna è risultata positiva. La presenza di HEV è stata valutata anche nelle salsicce di fegato, fresche e secche, acquistate presso una macelleria. Il genoma virale è stato rilevato nel 22,2% delle salsicce fresche e nel 4,3 % di quelle secche ma la vitalità del virus non è stata dimostrata. In conclusione, lo studio condotto ha confermato l’ampia circolazione di HEV nei suini e la possibile contaminazione dei prodotti carnei derivati, confermando la necessità di una continua sorveglianza.

Hereditary thrombotic thrombocytopenic purpura and the hereditary TTP registry

Hereditary thrombotic thrombocytopenic purpura, Upshaw-Schulman syndrome, ADAMTS13 Hereditary thrombotic thrombocytopenic purpura (TTP), also known as Upshaw-Schulman syndrome, is a rare recessively inherited disease. Underlying is a severe constitutional deficiency of the von Willebrand factor-cleaving protease, ADAMTS13, due to compound heterozygous or homozygous mutations in the ADAMTS13 gene. The clinical picture is variable and more and more patients with an adult-onset are diagnosed. In the majority of countries the only available treatment is plasma, which when administered regularly can efficiently prevent acute disease bouts. The decision to initiate regular prophylaxis is often not easy, as evidence based guidelines and long term outcome data are lacking. Through the hereditary TTP registry (www.ttpregistry.net, ClinicalTrials.gov identifier: NCT01257269), which was initiated in 2006 and is open to all patients diagnosed with Upshaw-Schulman syndrome and their family members, we aim to gain further information and insights into this rare disease, which eventually will help to improve clinical management of affected patients.

The mood-stabilizer lithium prevents hippocampal apoptosis and improves spatial memory in experimental meningitis.

Pneumococcal meningitis is associated with high morbidity and mortality rates. Brain damage caused by this disease is characterized by apoptosis in the hippocampal dentate gyrus, a morphological correlate of learning deficits in experimental paradigms. The mood stabilizer lithium has previously been found to attenuate brain damage in ischemic and inflammatory diseases of the brain. An infant rat model of pneumococcal meningitis was used to investigate the neuroprotective and neuroregenerative potential of lithium. To assess an effect on the acute disease, LiCl was administered starting five days prior to intracisternal infection with live Streptococcus pneumoniae. Clinical parameters were recorded, cerebrospinal fluid (CSF) was sampled, and the animals were sacrificed 42 hours after infection to harvest the brain and serum. Cryosections of the brains were stained for Nissl substance to quantify brain injury. Hippocampal gene expression of Bcl-2, Bax, p53, and BDNF was analyzed. Lithium concentrations were measured in serum and CSF. The effect of chronic lithium treatment on spatial memory function and cell survival in the dentate gyrus was evaluated in a Morris water maze and by quantification of BrdU incorporation after LiCl treatment during 3 weeks following infection. In the hippocampus, LiCl significantly reduced apoptosis and gene expression of Bax and p53 while it increased expression of Bcl-2. IL-10, MCP-1, and TNF were significantly increased in animals treated with LiCl compared to NaCl. Chronic LiCl treatment improved spatial memory in infected animals. The mood stabilizer lithium may thus be a therapeutic alternative to attenuate neurofunctional deficits as a result of pneumococcal meningitis.

Current insights into thrombotic microangiopathies: Thrombotic thrombocytopenic purpura and pregnancy.

The complex relation between thrombotic thrombocytopenic purpura (TTP) and pregnancy is concisely reviewed. Pregnancy is a very strong trigger for acute disease manifestation in patients with hereditary TTP caused by double heterozygous or homozygous mutations of ADAMTS13 (ADisintegrin And Metalloprotease with ThromboSpondin type 1 domains, no. 13). In several affected women disease onset during their first pregnancy leads to the diagnosis of hereditary TTP. Without plasma treatment mother and especially fetus are at high risk of dying. The relapse risk during a next pregnancy is almost 100% but regular plasma transfusion starting in early pregnancy will prevent acute TTP flare-up and may result in successful pregnancy outcome. Pregnancy may also constitute a mild risk factor for the onset of acute acquired TTP caused by autoantibody-mediated severe ADAMTS13 deficiency. Women having survived acute acquired TTP may not be at very high risk of TTP relapse during an ensuing next pregnancy but seem to have an elevated risk of preeclampsia. Monitoring of ADAMTS13 activity and inhibitor titre during pregnancy may help to guide management and to avoid disease recurrence. Finally, TTP needs to be distinguished from the much more frequent hypertensive pregnancy complications, preeclampsia and especially HELLP (Hemolysis, Elevated Liver Enzymes, Low Platelet count) syndrome.

Proteins mediating the Neospora caninum-host cell interaction as targets for vaccination

Neospora caninum is an apicomplexan parasite that is capable of infecting, a wide range of tissues. The fact that Neospora represents an important abortion-causing parasite in cattle has transformed neosporosis research from an earlier, rather esoteric field, to a significant research topic, and considerable investments have been made in the last years to develop an efficacious vaccine or other means of intervention that would prevent infection and abortion due to N. caninum infection in cattle. Antigenic molecules associated with proteins involved in adhesion/invasion or other parasite-host-cell interaction processes can confer protection against Neospora caninum infection, and such proteins represent valuable targets for the development of a vaccine to limit economical losses due to neosporosis. Although not ideal, small laboratory animal models that mimic cerebral infection, acute disease and fetal loss upon infection during pregnancy have been used for the assessment of vaccine candidates, in parallel with studies on experimental infections in cattle. Herein, we review and critically assess these vaccination approaches and discuss potential options for improvements.