Differential effects of antigens from L. braziliensis isolates from disseminated and cutaneous leishmaniasis on in vitro cytokine production

BACKGROUND: Disseminated leishmaniasis is an emerging infectious disease, mostly due to L. braziliensis, which has clinical and histopathological features distinct from cutaneous leishmaniasis. METHODS: In the current study we evaluated the in vitro production of the cytokines IFN-γ, TNF-α, IL-5 and IL-10 by peripheral blood mononuclear cells (PBMC) from 15 disseminated leishmaniasis and 24 cutaneous leishmaniasis patients upon stimulation with L. braziliensis antigens genotyped as disseminated leishmaniasis or cutaneous leishmaniasis isolates. RESULTS: Regardless of the source of L. braziliensis antigens, PBMC from cutaneous leishmaniasis patients produced significantly higher IFN-γ than PBMC from disseminated leishmaniasis patients. Levels of TNF-α by PBMC from cutaneous leishmaniasis patients were significantly higher than disseminated leishmaniasis patients only when stimulated by genotyped cutaneous leishmaniasis antigens. The levels of IL-5 and IL-10 production by PBMC were very low and similar in PBMCs from both disseminated leishmaniasis and cutaneous leishmaniasis patients. The immune response of each patient evaluated by the two L. braziliensis antigens was assessed in a paired analysis in which we showed that L. braziliensis genotyped as disseminated leishmaniasis isolate was more potent than L. braziliensis genotyped as cutaneous leishmaniasis isolate in triggering IFN-γ and TNF-α production in both diseases and IL-5 only in cutaneous leishmaniasis patients. CONCLUSION: This study provides evidence that antigens prepared from genotypically distinct strains of L. braziliensis induce different degrees of immune response. It also indicates that both parasite and host play a role in the outcome of L. braziliensis infection

Muscle strength and mortality while on a liver transplant waiting list

OBJETIVO: Avaliar a força de músculos respiratórios e de mão em pacientes na lista de espera para o transplante de fígado e associá-los a mortalidade. MATERIAIS E MÉTODOS: Foram estudados retrospectivamente 132 pacientes submetidos à avaliação fisioterapêutica de rotina e que esperavam o transplante de fígado. A força dos músculos ventilatórios foi avaliada por meio das pressões inspiratória e expiratória máximas e a força do membro superior por meio de dinamometria. Os pacientes foram divididos em dois grupos: grupo A, com 51 pacientes (14 mulheres, 50,1±12,3 anos) que morreram enquanto estavam na lista de espera e grupo B, com 81 pacientes (31 mulheres, 45,0±3,8 anos) que sobreviveram até o transplante de fígado. Foi utilizado o teste de t de Student com nível de significância de 5%. RESULTADOS: Os valores médios da pressão inspiratória máxima (PImax) dos grupos A e B foram 65,7±28,0 e 77,5±33,8mmHg (p=0,04), respectivamente, e as pressões expiratórias máximas foram 72,9±32,9 e 84,4±33,1mmHg (p=0,07), respectivamente. Os valores médios da força da mão esquerda dos grupos A e B foram 18,5±8,1 e 21,5±10,5kgf (p=0,08), respectivamente, e da força da mão direita foram 20,2±9,7 e 23,5±12,5kgf (p=0,10), respectivamente. CONCLUSÕES: A PImax é menor nos pacientes que morreram enquanto aguardavam o transplante. No mesmo grupo, foi observado que a pressão expiratória máxima e a força da mão direita e esquerda foram menores, apesar de não apresentarem diferenças estatisticamente significante.OBJECTIVE: To evaluate respiratory muscle strength and hand strength in patients on a liver transplant waiting list and to associate these with mortality. METHODS: one hundred and thirty-two patients who underwent routine physical therapy evaluation while waiting for liver transplantation were studied retrospectively. Respiratory muscle strength was assessed by measuring the maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP), and upper-limb strength was evaluated by dynamometry. The patients were divided into two groups: group A, consisting of 51 patients (14 females, 50.1±12.3 years) who died while on the waiting list; and group B, consisting of 81 patients (31 females, 45.0±3.8 years) who survived until the time of liver transplant. Student’s t test was used with a 5% significance level. RESULTS: The mean MIP values for groups A and B were 65.7±28.0 and 77.5±33.8mmHg (p=0.04), respectively, and the mean MEP values were 72.9±32.9 and 84.4±33.1mmHg (p=0.07), respectively. The mean values for left-hand strength in groups A and B were 18.5±8.1 and 21.5±10.5kgf (p=0.08), and the mean values for right-hand strength were 20.2±9.7 and 23.5±12.5kgf (p=0.10), respectively. CONCLUSIONS: MIP was lower in the patients who died while waiting for liver transplantation. In the same group, it was observed that the MEP values and right and left-hand strength were numerically lower, although they did not reach statistically significant differences

Diastolic Function Is Impaired in Patients With Prehypertension: Data From the EPIPorto Study

Introduction and objectives: Hypertension causes subclinical changes in left ventricular structure and function, namely diastolic dysfunction. Diastolic dysfunction is a predictor of heart failure, being involved in the association between hypertension and heart failure with preserved ejection fraction. We aimed to determine whether patients with prehypertension have early changes in diastolic function in a large community-based cohort of asymptomatic adults. Methods: A cross-sectional evaluation was performed of a community-based cohort consisting of 925 adults, aged 45 years or older, without known cardiovascular disease. All participants underwent detailed clinical and echocardiographic examination. The participants were categorized according to the European guidelines for the classification of office blood pressure (BP) levels as optimal, prehypertensive (normal and high-normal categories), and hypertensive. Diastolic function was evaluated by echocardiography using e’ velocities and E/e’ ratio. Diastolic dysfunction was defined using the 2016 ASE/EACVI Joint Recommendations and a 2017 clinically-oriented algorithm. Results: In this cohort (61.5 ± 10.5 years; 37% men), prehypertension was present in 30.4% and hypertension in 51.0%. Using optimal BP as the reference, there was a progressive decrease of e’ velocity in prehypertensive and hypertensive individuals (12.2 ± 3.5 vs 11.3 ± 3.1 vs 9.6 ± 2.9 cm/s, respectively; P for trend < .001). After multivariable adjustment, both BP categories were independent predictors of a lower e’ velocity (β = -0.56, P = .035 for prehypertension and β = –1.08, P < .001 for hypertension). Conclusions: In this large community-based cohort, adults with prehypertension already showed impaired cardiac relaxation before the onset of hypertension

Balance of IL-10 and Interferon-γ plasma levels in human visceral leishmaniasis: Implications in the pathogenesis

BACKGROUND: Leishmaniasis remains a serious public health problem in several parts of the developing world. Effective prophylactic measurements are hampered by imprecise comprehension of different aspects of the disease, including its immunoregulation. A better comprehension of immunoregulation in human VL may be useful both for designing and evaluating immunoprophylaxis. METHODS: To explore immunoregulatory mechanisms, 20 visceral leishmaniasis (VL) patients were evaluated during active disease and at different periods up to one year after treatment determining their plasma cytokine levels, clinical parameters (palpable spleen and liver) and antibody levels. RESULTS: Elevated plasma levels of IFN-γ and of IL-12 p40 were observed during active disease, significantly decreasing after treatment whereas in vitro Leishmania antigen-stimulated IFN-γ production by PBMC exhibited an inverse pattern being low during disease and increasing steadily thereafter. Absence of IFN-γ activity is a hallmark of VL. The main candidate for blunting IFN-γ activity is IL-10, a cytokine highly elevated in plasma with sharp decrease after treatment. Activity of IL-10 is inferred by high levels of anti-Leishmania specific IgG1 and IgG3. TGF-β had elevated total, but not of active, levels lessening the likelihood of being the IFN-γ counterpart. Spleen or liver size presented a steady decrease but return to normal values at only 120 days after treatment. Anti-Leishmania IgG (total and subclasses) levels and DTH or Leishmania-stimulated lymphocyte proliferation conversion to positive also present a slow decrease after treatment. IL-6 plasma levels were elevated in only a few patients. CONCLUSION: Taken together our results suggest that IFN-γ and IL-10 are the molecules most likely involved in determining fate of disease. After treatment, there is a long delay before the immune profile returns to normal what precludes using plasma cytokine levels as criteria of cure as simpler clinical evaluations, as a palpable spleen or liver, can be used

Comportamento de Biomphalaria glabrata variantes albina e melânica frente à infecção pelo Schistosoma mansoni

The behaviour of the albino and melanic variants of Biomphalaria glabrata of Belo Horizonte (MG. Brazil) was studied comparatively, in terms of their respective susceptibilities to infection by Schistosoma mansoni of the same origin, through observation of the elimination of cercariae for a three-month period and the calculation of mortality and infection rates, in control and in infected snails. The number of amoebocytes, granulocytes and hyalinocytes in the circulating hemolymph during different periods of infection was analyzed. The evolution of the infection in the tissues was observed by means of histological cross-sections. The melanic variant showed greater susceptibility to infection and a higher mortality rate. The albino variant showed a higher number of circulating amoebocytes, both granulocytes and hyalinocytes. A higher number of degenerated sporocysts were seen in the histological cross-sections of the albino variant. The results suggest that the melanic variant of B. glabrata was more susceptible to infection by S. mansoni than was the albino variant.Foi estudado comparativamente o comportamento das variantes albina e melânica de Biomphalaria glabrata de Belo Horizonte (MG. Brasil), em relação à susceptibilidade à infecção pelo Schistosoma mansoni de mesma origem, através da observação da eliminação de cercárias por um período de três meses e a verificação das taxas de mortalidade e infecção nos moluscos controles e infectados. Analisou-se também, o número de amebócitos granulócitos e hialinócitos na hemolinfa circulante em diferentes períodos de infecção. A evolução da infecção nos tecidos foi observada através de cortes histológicos. A variante melânica apresentou maior susceptibilidade à infecção e maior taxa de mortalidade. A variante albina apresentou maior número de amebócitos circulantes, tanto granulócitos quanto hialinócitos. Nos cortes histológicos foi verificado maior número de esporocistos degenerados na variedade albina. Por estes resultados sugere-se que nas populações estudadas a variante melânica de B. glabrata, foi mais susceptível à infecção pelo S. mansoni.21722

Evidence That Lipopolisaccharide May Contribute to the Cytokine Storm and Cellular Activation in Patients with Visceral Leishmaniasis

Visceral leishmaniasis (VL) affects organs rich in lymphocytes, being characterized by intense Leishmania-induced T-cell depletion and reduction in other hematopoietic cells. In other infectious and non-infectious diseases in which the immune system is affected, such as HIV-AIDS and inflammatory bowel disease, damage to gut-associated lymphocyte tissues occurs, enabling luminal bacteria to enter into the circulation. Lipopolisaccharide (LPS) is a bacterial product that stimulates macrophages, leading to the production of pro-inflammatory cytokines and other soluble factors such as MIF, which in turn activate lymphocytes. Continuous and exaggerated stimulation causes exhaustion of the T-cell compartment, contributing to immunosuppression

Higher order derivatives and norms of certain matrix functions

Tese de doutoramento, Matemática (Álgebra Lógica e Fundamentos), Universidade de Lisboa, Faculdade de Ciências, 2014In this thesis we obtain formulas for higher order directional derivatives for the immanant map, which is a generalization of the determinant and the permanent maps. We also obtain formulas for the k-th derivative of the m-th Х-symmetric tensor power of an operator or a matrix, where Х is an irreducible character of the permutation group Sm. Moreover, we calculate the operator norm of these derivatives. We start by presenting some general concepts of multilinear algebra, representation theory and matrix analysis, in particular some results about characters of Sm and differential calculus applied to matrix functions, which will be useful throughout this work. We also present some well known results about the immanant map, as well as other results such as the generalized Laplace expansion for immanants. The starting point of this kind of problems is the famous Jacobi formula obtained in the 19th century by Carl Jacobi. This formula gives us the first order derivative of the determinant function. In recent work, R. Bhatia, T. Jain and P. Grover [9], [8] presented us formulas for higher order derivatives of the determinant and the permanent maps and also the expressions for the derivatives of the symmetric and antisymmetric tensor powers. These maps are all particular cases of the immanant and the Х symmetric tensor power, when Х is a linear character of Sm, namely the principal and alternating characters. The general case has much more complicated features and needs some new concepts and notations, which play a very important role throughout our work. We also study the norm of these higher order derivatives. This problem was first addressed by R. Bhatia and S. Friedland in [7] where they proved a formula for D ^m (A). This result has been extended in two different directions. In [9], R. Bhatia and T. Jain study the case for higher order derivatives and they obtain a formula for the norm of Dk ^m (A), whereas in [6], R. Bhatia and J. A. Dias da Silva demonstrate a formula for the norm of the first derivative for all symmetry classes. In our work we obtain a result that subsumes all the previous expression