Fonsecaea pedrosoi infection induces differential modulation of costimulatory molecules and cytokines in monocytes from patients with severe and mild forms of chromoblastomycosis

The host defense mechanism in chromoblastomycosis has not been thoroughly investigated. It has been suggested that cell- mediated immunity in patients with long- standing chromoblastomycosis is somehow impaired. As a result, these individuals became unable to develop an efficient immune reaction. Many studies have shown that monocyte- derived macrophages exhibit critical activities in immunity to microorganisms. Moreover, the ability of cells from the monocytic lineage to process and present antigens, to produce cytokines, and to provide costimulatory signals confirms their pivotal role in the initiation of specific immune responses. In the present study, it was observed that monocytes from patients with a severe form of disease had a higher production of IL- 10 and a lower expression of HLA- DR and costimulatory molecules when stimulated with specific antigen or LPS. Immune modulation with recombinant IL- 12 or anti- IL- 10 can restore the antigen- specific Th1- type immune response in chromoblastomycosis patients by up- regulating HLA- DR and costimulatory molecules in monocytes. Therefore, our data show that monocytes from patients with different clinical forms of chromoblastomycosis present distinct phenotypic and functional profiles. This observation suggests possible mechanisms that control the T cell response and influence their role in the development of pathology.

GEVREY SOLVABILITY AND GEVREY REGULARITY IN DIFFERENTIAL COMPLEXES ASSOCIATED TO LOCALLY INTEGRABLE STRUCTURES

In this work we study some properties of the differential complex associated to a locally integrable (involutive) structure acting on forms with Gevrey coefficients. Among other results we prove that, for such complexes, Gevrey solvability follows from smooth solvability under the sole assumption of a regularity condition. As a consequence we obtain the proof of the Gevrey solvability for a first order linear PDE with real-analytic coefficients satisfying the Nirenberg-Treves condition (P).

INDEX OF AN IMPLICIT DIFFERENTIAL EQUATION

In this paper we introduce the concept of the index of an implicit differential equation F(x,y,p) = 0, where F is a smooth function, p = dy/dx, F(p) = 0 and F(pp) = 0 at an isolated singular point. We also apply the results to study the geometry of surfaces in R(5).

Protein variation in blood-dwelling schistosome worms generated by differential splicing of micro-exon gene transcripts

Schistosoma mansoni is a well-adapted blood-dwelling parasitic helminth, persisting for decades in its human host despite being continually exposed to potential immune attack. Here, we describe in detail micro-exon genes (MEG) in S. mansoni, some present in multiple copies, which represent a novel molecular system for creating protein variation through the alternate splicing of short (<= 36 bp) symmetric exons organized in tandem. Analysis of three closely related copies of one MEG family allowed us to trace several evolutionary events and propose a mechanism for micro-exon generation and diversification. Microarray experiments show that the majority of MEGs are up-regulated in life cycle stages associated with establishment in the mammalian host after skin penetration. Sequencing of RT-PCR products allowed the description of several alternate splice forms of micro-exon genes, highlighting the potential use of these transcripts to generate a complex pool of protein variants. We obtained direct evidence for the existence of such pools by proteomic analysis of secretions from migrating schistosomula and mature eggs. Whole-mount in situ hybridization and immunolocalization showed that MEG transcripts and proteins were restricted to glands or epithelia exposed to the external environment. The ability of schistosomes to produce a complex pool of variant proteins aligns them with the other major groups of blood parasites, but using a completely different mechanism. We believe that our data open a new chapter in the study of immune evasion by schistosomes, and their ability to generate variant proteins could represent a significant obstacle to vaccine development.

Drug Excipient Interaction Study with Polymorphic Forms of Tibolone

Powder mixtures (1:1) of tibolone polymorphic forms I (monoclinic) and II (triclinic) and excipients have been prepared and compacted. The samples were stored at 50 degrees C and 90% RH for one month and subsequently were evaluated using differential scanning calorimetry (DSC) and high-performance liquid chromatography (HPLC). The results indicate that during the compaction, the applied pressure reduced the chemical stability of tibolone in both polymorph forms. The triclinic form was more chemically unstable, both pure and in contact with excipients, than the monoclinic form. Lactose monohydrate was shown to reduce chemical degradation for both forms. Ascorbyl palmitate was shown to affect the tibolone stability differently depending on the polymorphic form used.

Caracterização mecânica e térmica da borracha natural formulada e vulcanizada dos clones: GT 1, IAN 873, PB 235 e RRIM 600

Neste trabalho estudou-se o desempenho mecânico e térmico de compostos de borracha natural (Hevea brasiliensis) de 4 diferentes clones (GT 1, IAN 873, PB 235 e RRIM 600) cultivados no Estado de São Paulo, assim como de uma mistura destes clones e de uma borracha comercial, GEB-1. Estas borrachas foram formuladas e vulcanizadas com tempos de 5, 7 e 9 minutos. A caracterização foi realizada por calorimetria exploratória diferencial, termogravimetria, ensaios de resistência à tração, análise dinâmico-mecânica, medidas de dureza Shore A, microscopia eletrônica de varredura e espectroscopia na região do infravermelho. Os resultados permitiram concluir que o tempo de vulcanização e o tipo de clone não influenciaram na temperatura de transição vítrea (Tg) dos compostos. Os valores de Tg obtidos por DMA foram de cerca de -62 °C, e os resultados ensaios de dureza apresentaram valores próximos de 60 para todos os compostos estudados. Os ensaios de resistência à tração mostraram que o melhor desempenho mecânico foi obtido pelo clone RRIM 600. De acordo com os resultados obtidos neste trabalho, todos os clones atingiram as propriedades reportadas na literatura, podendo ser utilizados, em princípio, nas indústrias de artefatos de borracha separadamente ou na forma de mistura.

Inpatient dermatological consultations in a university hospital

INTRODUCTION: Dermatology is primarily an outpatient specialty, but it also plays an important role in the care of inpatients. METHODS: We conducted a prospective study that recorded data from inpatient dermatology consultation request forms over a period of four months. The study evaluated 313 requests that led to 566 visits, 86 biopsies, 35 laboratory exams, 41 direct microscopic studies, 18 direct immunofluorescence analyses, 14 skin cultures and a few other exams. RESULTS: The most frequent requesting service was internal medicine (24%), followed by neurology (12%), cardiology (11%), infectious diseases and pediatrics (8% each) and psychiatry and general surgery (6% each). The most frequent diagnostic groups were infectious diseases (25%, divided into fungal infections (13%), bacterial infections (7%) and viral infections (5%)), eczemas (15%) and drug reactions (14%). To our knowledge, this is the first study to attempt to evaluate the impact of the consultations by asking multiple-choice questions that were analyzed by the authors. In 31% of the cases, the consultation was considered extremely relevant because it aided in managing the disease that led to admission or treated a potentially severe dermatological disease. In 58% of the cases, the consultation was considered important because it facilitated diagnosis and/or treatment of a dermatological disease that was unrelated to the reason for admission.

Interleukin-22 forms dimers that are recognized by two interleukin-22R1 receptor chains

Interleukin-22 (IL-22) is a class 2 cytokine whose primary structure is similar to that of interleukin 10 (IL-10) and interferon-gamma (IFN-gamma). IL-22 induction during acute phase immune response indicates its involvement in mechanisms of inflammation. Structurally different from IL-10 and a number of other members of IL-10 family, which form intertwined inseparable V-shaped dimers of two identical polypeptide chains, a single polypeptide chain of IL-22 folds on itself in a relatively globular structure. Here we present evidence, based on native gel electrophoresis, glutaraldehyde cross-linking, dynamic light scattering, and small angle x-ray scattering experiments, that human IL-22 forms dimers and tetramers in solution under protein concentrations assessable by these experiments. Unexpectedly, low-resolution molecular shape of IL-22 dimers is strikingly similar to that of IL-10 and other intertwined cytokine dimeric forms. Furthermore, we determine an ab initio molecular shape of the IL-22/IL-22R1 complex which reveals the V-shaped IL-22 dimer interacting with two cognate IL-22R1 molecules. Based on this collective evidence, we argue that dimerization might be a common mechanism of all class 2 cytokines for the molecular recognition with their respective membrane receptor. We also speculate that the IL-22 tetramer formation could represent a way to store the cytokine in nonactive form at high concentrations that could be readily converted into functionally active monomers and dimers upon interaction with the cognate cellular receptors.

An Extension of the Invariance Principle for a Class of Differential Equations with Finite Delay

An extension of the uniform invariance principle for ordinary differential equations with finite delay is developed. The uniform invariance principle allows the derivative of the auxiliary scalar function V to be positive in some bounded sets of the state space while the classical invariance principle assumes that. V <= 0. As a consequence, the uniform invariance principle can deal with a larger class of problems. The main difficulty to prove an invariance principle for functional differential equations is the fact that flows are defined on an infinite dimensional space and, in such spaces, bounded solutions may not be precompact. This difficulty is overcome by imposing the vector field taking bounded sets into bounded sets.

EXISTENCE RESULTS FOR NEUTRAL INTEGRO-DIFFERENTIAL EQUATIONS WITH UNBOUNDED DELAY

In this paper we discuss the existence of mild, strict and classical solutions for a class of abstract integro-differential equations in Banach spaces. Some applications to ordinary and partial integro-differential equations are considered.

Existence Results for Abstract Partial Neutral Integro-differential Equation with Unbounded Delay

In this paper we study the existence and regularity of mild solutions for a class of abstract partial neutral integro-differential equations with unbounded delay.

GLOBAL SOLUTIONS FOR ABSTRACT FUNCTIONAL DIFFERENTIAL EQUATIONS WITH NONLOCAL CONDITIONS

In this paper we study the existence of global solutions for a class of abstract functional differential equation with nonlocal conditions. An application is considered.

Weighted S-Asymptotically omega-Periodic Solutions of a Class of Fractional Differential Equations

We study the existence of weighted S-asymptotically omega-periodic mild solutions for a class of abstract fractional differential equations of the form u' = partial derivative (alpha vertical bar 1)Au + f(t, u), 1 < alpha < 2, where A is a linear sectorial operator of negative type.

EXISTENCE RESULTS FOR ABSTRACT NEUTRAL FUNCTIONAL DIFFERENTIAL EQUATIONS

In this paper we discuss the existence of solutions for a class of abstract partial neutral functional differential equations.

Differential regulation of PGC-1 alpha expression in rat liver and skeletal muscle in response to voluntary running

Background: The beneficial actions of exercise training on lipid, glucose and energy metabolism and insulin sensitivity appear to be in part mediated by PGC-1 alpha. Previous studies have shown that spontaneously exercised rats show at rest enhanced responsiveness to exogenous insulin, lower plasma insulin levels and increased skeletal muscle insulin sensitivity. This study was initiated to examine the functional interaction between exercise-induced modulation of skeletal muscle and liver PGC-1 alpha protein expression, whole body insulin sensitivity, and circulating FFA levels as a measure of whole body fatty acid (lipid) metabolism. Methods: Two groups of male Wistar rats (2 Mo of age, 188.82 +/- 2.77 g BW) were used in this study. One group consisted of control rats placed in standard laboratory cages. Exercising rats were housed individually in cages equipped with running wheels and allowed to run at their own pace for 5 weeks. At the end of exercise training, insulin sensitivity was evaluated by comparing steady-state plasma glucose (SSPG) concentrations at constant plasma insulin levels attained during the continuous infusion of glucose and insulin to each experimental group. Subsequently, soleus and plantaris muscle and liver samples were collected and quantified for PGC-1 alpha protein expression by Western blotting. Collected blood samples were analyzed for glucose, insulin and FFA concentrations. Results: Rats housed in the exercise wheel cages demonstrated almost linear increases in running activity with advancing time reaching to maximum value around 4 weeks. On an average, the rats ran a mean (Mean +/- SE) of 4.102 +/- 0.747 km/day and consumed significantly more food as compared to sedentary controls (P < 0.001) in order to meet their increased caloric requirement. Mean plasma insulin (P < 0.001) and FFA (P < 0.006) concentrations were lower in the exercise-trained rats as compared to sedentary controls. Mean steady state plasma insulin (SSPI) and glucose (SSPG) concentrations were not significantly different in sedentary control rats as compared to exercise-trained animals. Plantaris PGC-1 alpha protein expression increased significantly from a 1.11 +/- 0.12 in the sedentary rats to 1.74 +/- 0.09 in exercising rats (P < 0.001). However, exercise had no effect on PGC-1 alpha protein content in either soleus muscle or liver tissue. These results indicate that exercise training selectively up regulates the PGC-1 alpha protein expression in high-oxidative fast skeletal muscle type such as plantaris muscle. Conclusion: These data suggest that PGC-1 alpha most likely plays a restricted role in exercise-mediated improvements in insulin resistance (sensitivity) and lowering of circulating FFA levels.