Lower cytokine secretion ex vivo by natural killer T cells in HIV-infected individuals is associated with higher CD161 expression

Objective: Natural killer T (NKT) cells are efficiently targeted by HIV and severely reduced in numbers in the circulation of infected individuals. The functional capacity of the remaining NKT cells in HIV-infected individuals is poorly characterized. This study measured NKT cell cytokine production directly ex vivo and compared these responses with both the disease status and NKT subset distribution of individual patients. Methods: NKT cell frequencies, subsets, and ex-vivo effector functions were measured in the peripheral blood mononuclear cells of HIV-infected patients and healthy controls by flow cytometry. We measured cytokines from NKT cells after stimulation with either a-galactosyl ceramide-loaded CD1d dimers (DimerX-alpha GalCer) or phorbol myristate acetate and ionomycin. Results: The frequencies of NKT cells secreting interferon-gamma and tumor necrosis factor-alpha were significantly lower in HIV-infected patients than healthy controls after DimerX-alpha GalCer treatment, but responses were similar after treatment with phorbol myristate acetate and ionomycin. The magnitude of the interferon-gamma response to DimerX-alpha GalCer correlated inversely with the number of years of infection. Both interferon-gamma and tumor necrosis factor-alpha production in response to DimerX-alpha GalCer correlated inversely with CD161 expression. Conclusion: The ex-vivo Th1 responses of circulating NKT cells to CD1d-glycolipid complexes are impaired in HIV-infected patients. NKT cell functions may be progressively lost over time in HIV infection, and CD161 is implicated in the regulation of NKT cell responsiveness. (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins

TGFB1 and IL8 gene polymorphisms and susceptibility to visceral leishmaniasis

Visceral leishmaniasis (VL) or Kala-azar is a serious protozoan infectious disease caused by an obligate intracellular parasite. Cytokines have a major role in determining progression and severity of clinical manifestations in VL. We investigated polymorphisms in the TGFB1 and IL8 genes, which are cytokines known to have a role in onset and severity of the disease. Polymorphisms at TGFB1 -509 C/T and +869 T/C, and IL8 -251 A/T were analyzed by a PCR-RFLP technique, in 198 patients with VL, 98 individuals with asymptomatic infection positive for a delayed-type hypersensitivity test (DTH+) and in 101 individuals with no evidence of infection (DTH-). The presence of the T allele in position -509 of the TGFB1 gene conferred a two-fold risk to develop infection both when including those with clinical symptoms (DTH+ and VL, grouped) or when considering DTH+ only, respectively p = 0.007, OR = 1.9 [1.19-3.02] and p = 0.012, OR = 2.01 [1.17-3.79], when compared with DTH- individuals. In addition, occurrence of hemorrhage was associated with TGFB1 -509 T allele. We suggest that the -509 T allele of the TGFB1 gene, a cytokine with a biologically relevant role in the natural history of the disease, may contribute to overall susceptibility to infection by Leishmania and to severity of the clinical disease. (C) 2011 Elsevier B.V. All rights reserved.

The love of a sage or the command of a superior: The natural law doctrines of Leibniz and Pufendorf

The study of natural law theories is presently one of the most fruitful areas of research in the studies of early modern intellectual history, and moral and political theory. Likewise the historical significance of the Enlightenment for the development of modernisation' in many different forms continues to be the subject of controversy. This collection therefore offers a timely opportunity to re-examine both the coherence of the concept of an early Enlightenment', and the specific contribution of natural law theories to its formation. The works of major thinkers such as Grotius, Hobbes, Locke, Malebranche, Pufendorf and Thomasius are reassessed, and the appeal and importance of the discourse of natural jurisprudence both to those working inside conventional educational and political structures and to those outside - such as in the Huguenot diaspora - is evaluated. This volume will therefore be of importance to all those readers concerned to study the character of the debates in the period 1650-1750 surrounding moral and political agency, sovereignty and obligation, and the legitimation of religious toleration in the divergent states and patriotic contexts of Europe.

Effects of sinoaortic Denervation on Hemodynamic parameters during natural sleep in rats

Study Objectives: To analyze the role of arterial baroreflex on hemodynamic changes during synchronized and desynchronized sleep phases of natural sleep in rats. Design: Experimental study. Setting: Laboratory. Participants: Seventeen male Wistar rats. Interventions: No intervention (control, n = 8) or sinoaortic denervation (SAD, n = 9). Measurements and Results: Sleep phases were monitored by electrocorticogram, and blood pressure was measured directly by a catheter in the carotid artery. Cardiac output, as well as total and regional vascular resistances, were determined by measuring the subdiaphragmatic aorta and iliac artery flows with Doppler flow probes, respectively. In contrast to the control group, the SAD group had a strong reduction in blood pressure (-19.9% +/- 2.6% vs -0.7% +/- 2.1%) during desynchronized sleep, and cardiac output showed an exacerbated reduction (-10.4% +/- 3.5% vs 1.1% +/- 1.7%). In SAD rats, total vascular resistance decreased during desynchronized sleep (-10.1% +/- 3.5% vs -1.0% +/- 1.7%), and the increase in regional vascular resistance observed in the control group was abolished (27.5% +/- 8.3% vs -0.8% +/- 9.4%). Conclusions: SAD caused profound changes in blood pressure, cardiac output, and total vascular resistance, with a significant increase in muscle vascular resistance during synchronized sleep. Our results suggest that baroreflex plays an important role in maintaining the normal balance of cardiac output and total vascular resistance during sleep.

Intracranial vascular lesions associated with small epidural hematomas

OBJECTIVE: We studied the angiographic findings in patients with small epidural hematomas and cranial fractures crossing over the trajectory of the middle meningeal artery and its branches. Additionally, the Occurrence of traumatic vascular lesions and their clinical relevance and treatment are discussed. METHODS: A consecutive analysis was performed for 24 patients who harbored small epidural hematomas in middle meningeal artery topography associated with cranial fractures. Computed tomographic scans and plain x-ray studies were used to diagnose linear cranial fractures. Patients with large epidural hematomas or associated traumatic lesions were excluded from the study. Selective ipsilateral external carotid angiograms were obtained, and an endovascular procedure was performed if any vascular injury was evidenced. RESULTS: In all patients with cranial fractures crossing over the middle meningeal artery and its branches, some kind of vascular lesion was seen. Two types of findings were noted: active extravasation of the contrast medium (71%) and pseudoaneurysms (29%). Early filling of diploic vessels was found in 8.3% of fractures concomitantly with active extravasation. Embolization was performed in all patients. No additional enlargement of the epidural hematoma was observed, and the postoperative period was uneventful. CONCLUSION: This study shows that pseudoaneurysms and active extravasation of contrast are common findings in this subset of patients. Although the natural history of these lesions is still poorly understood, additional investigation with ipsilateral external carotid angiography may be recommended, considering the potentially catastrophic consequences of late rupture.

Prenatal diagnosis and natural history of fetuses presenting with pleural effusion

Objective To describe the natural history of fetuses presenting with pleural effusion. Methods Between January 2005 and December 2009 all fetuses diagnosed with pleural effusion were followed up. Fetuses were divided into three groups: I, isolated pleural effusion; II, associated structural anomalies but normal karyotype; and III, chromosomal anomalies. Univariate and multivariate analyses were performed to determine the association between prenatal ultrasound findings and perinatal death. Results Fifty-six fetuses were included in the study. Associated structural or chromosomal anomalies occurred in 75.0% (42/56) of cases. Bilateral pleural effusion and fetal hydrops were associated with each other (p < 0.01) and with perinatal death (p < 0.05). Multivariate analysis indicated that only the presence of associated abnormalities was a statistical determinant of perinatal death (OR, 3.56; 95% CI, 1.48-5.64; p < 0.01). Conclusion Fetal pleural effusion is often associated with other abnormalities, and this association has poor perinatal outcome. Copyright (C) 2011 John Wiley & Sons, Ltd.

Evaluation of rhBMP-2 and Natural Latex as Potential Osteogenic Proteins in Critical Size Defects by Histomorphometric Methods

This in vivo study evaluated the osteogenic potential of two proteins, recombinant human bone morphogenetic protein-2 (rhBMP-2) and a protein extracted from natural latex (Hevea brasiliensis, P-1), and compared their effects on bone defects when combined with a carrier or a collagen gelatin. Eighty-four (84) Wistar rats were divided into two groups, with and without the use of collagen gelatin, and each of these were divided into six treatment groups of seven animals each. The treatment groups were: (1) 5 mu g of pure rhBMP-2; (2) 5 mu g of rhBMP-2/monoolein gel; (3) pure monoolein gel; (4) 5 mu g of pure P-1; (5) 5 mu g of P-1/monoolein gel; (6) critical bone defect control. The animals were anesthetized and a 6 mm diameter critical bone defect was made in the left posterior region of the parietal bone. Animals were submitted to intracardiac perfusion after 4 weeks and the calvaria tissue was removed for histomorphometric analysis. In this experimental study, it was concluded that rhBMP-2 allowed greater new bone formation than P-1 protein and this process was more effective when the bone defect was covered with collagen gelatin (P < 0.05). Anat Rec, 293:794-801, 2010. (C) 2010 Wiley-Liss, Inc.

Increased Vascular Permeability, Angiogenesis and Wound Healing Induced by the Serum of Natural Latex of the Rubber Tree Hevea brasiliensis

Increases in vascular permeability and angiogenesis are crucial events to wound repair, tumoral growth and revascularization of tissues submitted to ischemia. An increased vascular permeability allows a variety of cytokines and growth factors to reach the damaged tissue. Nevertheless, the angiogenesis supply tissues with a wide variety of nutrients and is also important to metabolites clearance. It has been suggested that the natural latex from Hevea brasiliensis showed wound healing properties and angiogenic activity. Thus, the purpose of this work was to characterize its angiogenic activity and its effects on vascular permeability and wound healing. The serum fraction of the latex was separated from the rubber with reduction of the pH. The activity of the dialyzed serum fraction on the vascular permeability injected in subcutaneous tissue was assayed according Mile`s method. The angiogenic activity was determined using a chick embryo chorioallantoic membrane assay and its effects on the wound-healing process was determined by the rabbit ear dermal ulcer model. The serum fraction showed evident angiogenic effect and it was effective in enhancing vascular permeability. In dermal ulcers, this material significantly accelerated wound healing. Moreover, the serum fraction boiled and treated with proteases lost these activities. These results are in accordance with the enhancement of wound healing observed in clinical trials carried out with a biomembrane prepared with the same natural latex. Copyright (C) 2009 John Wiley & Sons, Ltd.

Natural Host Relationships and Genetic Diversity of Rodent-Associated Hantaviruses in Southeastern Brazil

Objective: Hantaviruses are rodent-borne RNA viruses that have caused hantavirus cardiopulmonary syndrome in several Brazilian regions. In the present study, geographical distribution, seroprevalence, natural host range, and phylogenetic relations of rodent-associated hantaviruses collected from seven counties of Southeastern Brazil were evaluated. Methods: ELISA, RT-PCR and phylogenetic analysis were used in this study. Results: Antibodies to hantavirus were detected in Bolomys lasiurus, Akodon sp. and Oligoryzomys sp., performing an overall seroprevalence of 5.17%. All seropositive rodents were associated with grasslands or woods surrounded by sugar cane fields. Phylogenetic analysis of partial S- and M-segment sequences showed that viral sequences isolated from B. lasiurus specimens clustered with Araraquara virus. However, a sequence from Akodon sp. shared 100% similarity with Argentinian/Chilean viruses based on the partial S- segment amino acid sequence. Conclusion: These results indicate that there are associations between rodent reservoirs and hantaviruses in some regions of Southeastern Brazil, and suggest the existence of additional hantavirus genetic diversity and host ecology in these areas. Copyright (C) 2008 S. Karger AG, Basel