Relação entre Resposta Imune Inata do Receptor Toll-Like-4 (TLR-4) e o Processo Fisiopatológico da Cardiomiopatia da Obesidade

BackgroundObesity is a chronic low-grade inflammation condition related to cardiac disorders. However, the mechanism responsible for obesity-related cardiac inflammation is unclear. The toll-like receptor 4 (TLR-4) belongs to a receptor of the transmembrane family responsible for the immune response whose activation stimulates the production of proinflammatory cytokines.ObjectiveTo test whether the activation of the TLR-4 receptor participates in the obesity cardiomyopathy process, due to cytokine production through NF-ĸB activation.MethodsMale Wistar rats were randomized into two groups: the control group (C, n= 8 animals) that received standard diet/water and the obese group (OB, n= 8 animals) that were fed a high sugar-fat diet and water plus 25% of sucrose for 30 weeks. Nutritional analysis: body weight, adiposity index, food, water, and caloric intake. Obesity-related disorders analysis: plasma glucose, uric acid and triglycerides, HOMA-IR, systolic blood pressure, TNF-α in adipose tissue. Cardiac analysis included: TLR-4 and NF-ĸB protein expression, TNF-α and IL-6 levels. Comparison by unpaired Student’s t-test or Mann- Whitney test with a p-value < 0.05 as statistically significant.ResultsThe OB group showed obesity, high glucose, triglycerides, uric acid, HOMA, systolic blood pressure, and TNF-α in adipose tissue. OB group presented cardiac remodeling and diastolic dysfunction. TLR-4 and NF-ĸB expression and cytokine levels were higher in OB.ConclusionOur findings conclude that, in an obesogenic condition, the inflammation derived from cardiac TLR-4 activation can be a mechanism able to lead to remodeling and cardiac dysfunction.     

Epidemiology, characteristics, and outcome of infective endocarditis in Italy: the Italian Study on Endocarditis

Background

The characteristics of patients with infective endocarditis (IE) vary significantly by region of the world. The aim of this study was to evaluate the contemporary epidemiology, characteristics, and outcome of IE in a large, nationwide cohort of Italian patients.

Methods

We conducted a prospective, observational study at 24 medical centers in Italy, including all the consecutive patients with a definite or possible diagnosis of IE (modified Duke criteria) admitted from January 2004 through December 2009. A number of clinical variables were collected through an electronic case report form and analyzed to comprehensively delineate the features of IE. We report the data on patients with definite IE.

Results

A total of 1,082 patients with definite IE were included. Of these, 753 (69.6?%) patients had infection on a native valve, 277 (25.6?%) on a prosthetic valve, and 52 (4.8?%) on an implantable electronic device. Overall, community-acquired (69.2?%) was more common than nosocomial (6.2?%) or non-nosocomial (24.6?%) health care-associated IE. Staphylococcus aureus was the most common pathogen (22.0?%). In-hospital mortality was 15.1?%. From the multivariate analysis, congestive heart failure (CHF), stroke, prosthetic valve infection, S. aureus, and health care-associated acquisition were independently associated with increased in-hospital mortality, while surgery was associated with decreased mortality.

Conclusions

The current mortality of IE remains high, and is mainly due to its complications, such as CHF and stroke.     

Autologous transplantation of chemotherapy-purged PBSC collections from high-risk leukemia patients: a pilot study

We have recently demonstrated that the combination of the alkylating agent nitrogen mustard (NM) and etoposide (VP-16) is capable of eliminating, ex vivo, leukemic cells contaminating PBSC collections and this is associated with a significant recovery of primitive and committed hematopoietic progenitor cells. Based on these data a pilot study on autologous transplantation of NM/VP-16 purged PBSC for high-risk leukemic patients was recently initiated. Twelve patients (seven females and five males) with a median age of 46 years (range 18-57) have been treated. Two patients had acute myeloblastic leukemia (AML) resistant to conventional induction treatment, four patients had secondary AML in I complete remission (CR), one patient was in II CR after failing a previous autologous BM transplantation, while two additional AML individuals were in I CR achieved after three or more cycles of induction treatment. Two patients with high-risk acute lymphoblastic leukemia (ALL) in I CR and one patient with mantle cell lymphoma and leukemic dissemination were also included. Eight patients showed karyotypic abnormalities associated with a poor clinical outcome. The mobilizing regimens included cytosine arabinoside and mitoxantrone with (n = 6) or without fludarabine (n = 3) followed by subcutaneous administration of G-CSF (5 microg/kg/day until the completion of PBSC collection) and G-CSF alone (n = 3) (15 microg/kg/day). A median of two aphereses (range 1-3) allowed the collection of 7.2 x 10(8) TNC/kg (range 3.4-11.5), 5 x 10(6) CD34+ cells/kg (range 2.1-15.3) and 9.2 x 10(4) CFU-GM/kg (0.3-236). PBSC were treated with a constant dose of 20 microg of VP-16/ml and a median individual-adjusted dose (survival < or = 5% of steady-state BM CFU-GM) of NM of 0.7 microg/ml (range 0.25-1.25). Eleven patients were reinfused after busulfan (16 mg/kg) and Cy (120 mg/kg) conditioning with a median residual dose of 0.3 x 10(4) CFU-GM/kg (0-11.5). The median time to neutrophil engraftment (>0.5 x 10(9)/l) for evaluable patients was 25 days (range 12-59); the median time to platelet transfusion independence (>20 and >50 x 10(9)/l) was 40 days (18-95) and 69 days (29-235), respectively. Hospital discharge occurred at a median of 25 days (18-58) after stem cell reinfusion. Four individuals are alive in CR (n = 3) or with residual nodal disease (n = 1 lymphoma patient) with a follow-up of 32, 26, 3 and 14 months, respectively. Seven patients died due to disease progression or relapse (n = 5) or extrahematological transplant toxicity (n = 2). Our data suggest that pharmacological purging of leukapheresis collections of leukemic patients at high-risk of relapse is feasible and ex vivo treated cells reconstitute autologous hematopoiesis.     

91例胃粘膜EB病毒感染的检测

ＥＢ病毒是一种肿瘤病毒，与人类鼻咽癌、淋巴瘤关系密切。近年来ＥＢ病毒相关性胃癌在国外已有报道。本文通过胃镜活检，对９１例胃粘膜行ＰＣＲ方法检测ＥＢ病毒感染。一、材料与方法：９１例患者均为我院１９９６年３月～６月门诊及住院胃镜检查者。男５８例，女３３例...     

In vitro effects of bisantrene on fresh clonogenic leukemia cells: a preliminary study on 15 cases

In vitro clonogenic assays may be useful for determining the sensitivity of leukemic cells to chemotherapeutic agents. We evaluated the antileukemic effect of Bisantrene (an anthracene derivative now undergoing phase II clinical trials in relapsed/resistant acute non lymphoid leukemias-ANLL) using the ANLL cell clonogenic assay. Fifteen cases were studied (9 newly diagnosed, 5 relapsed and 1 refractory ANLL). Normal CFU-GM sensitivity was tested in a subset of 10 normal controls. A wide range of concentrations (from 0.01 to 10 micrograms/ml) at 3 durations of exposure (30 min, 120 min, continuous) was employed. Bisantrene proved effective in 12 out of 15 ANLL cases, inhibiting blast colony growth (50% at 1 micrograms/ml; nearly 100% at 10 micrograms/ml) in a dose-dependent, time-independent way. Three cases were unresponsive both in vitro and in vivo. Normal CFU-GM were inhibited at lower doses (50% at 0.5 micrograms/ml; 100% at 5 micrograms/ml). We conclude that: 1) Bisantrene is active in vitro on leukemic clonogenic cells at doses corresponding to plasmatic levels achievable in patients, with a parallel activity in vivo in 3 relapsed cases. It should be tested in vitro before therapeutic use in order to avoid, if possible, improper use in resistant patients. 2) Normal CFU-GM are more sensitive than clonogenic leukemic cells. This must be taken into account, in view of possible prolonged neutropenias after therapy. 3) The time-independent effect of the drug should be evaluated in the design of new therapeutic schedules.     

Behçet’s disease: an immune-mediated vasculitis involving vessels of all sizes

Behçet’s disease is an immune-mediated vasculitis affecting both small and large vessels. Small-vessel vasculitis is the pathological basis of the multiorgan involvement that results in protean clinical features. However, relapsing aphthous ulcers in the mouth are considered the clinical hallmark and are often also observed over the genitalia. Both manifestations, in association with uveitis, form the typical clinical triad. In addition, skeletal muscles, joints, gastrointestinal, cardiopulmonary, and central nervous systems can be involved. Heterogeneity in incidence, clinical manifestations, course, and seventy are observed according to ethnic background. The natural course is chronic with relapses and remissions, gradually abating over the years, but the illness can also be life or sight threatening. Its origin and cause are still obscure: genetic, infectious, environmental, and immunological factors have been proposed. Owing to the lack of a specific test, diagnosis still relies on recognition of the typical clinical pattern. Treatment usually includes corticosteroids and immunosuppressive drugs. A better understanding of the pathogenesis will hopefully improve both diagnosis and therapy. In addition, the development of tests aimed at monitoring disease activity and response to therapy is certainly desirable.