Evaluation of the cytokine mannose-binding lectin as a mediator of periportal fibrosis progression in patients with schistosomiasis

INTRODUCTION : We hypothesized higher mannose-binding lectin level and classic factors (i.e., age, sex, alcohol consumption, exposure, and specific treatment) are associated with the severity of periportal fibrosis in schistosomiasis. METHODS : This cross-sectional study involved 79 patients infected with Schistosoma mansoni with severe or mild/moderate periportal fibrosis. Serum concentrations of mannose-binding lectin were obtained by enzyme-linked immunosorbent assay (ELISA). RESULTS: Higher serum level of mannose-binding lectin was significantly associated with advanced periportal fibrosis. CONCLUSIONS: Mannose-binding lectin may contribute to liver pathology in schistosomiasis and may represent a risk factor for advanced periportal fibrosis in the Brazilian population studied.

The feature of papers and citation analysis of eleven journals in tropical medicine indexed by Science Citation Index Expanded

To determine the features of papers, authors, and citation of eleven journals in tropical medicine indexed by Science Citation Index Expanded, the database of the Institute for Scientific Information, we analyzed original articles, editorials, reviews, corrections, letters, biographies, and news published in these journals. The results show that these journals covered 107 countries or regions on six continents. The average number of reference was 23.05, with 87.89% of the references from periodicals. The Price Index was 31.43% and the self-citing rate was 7.02%. The references in the first 20 journals ranked by the amount of citation accounted for 36.71% of the total citations. Brazil, United States, India, and England are more advanced in tropical medicine research. The conclusion is that these journals covered most research done in these countries or regions. Most researches were done by cooperation of the researchers, but many of the publications used outdated articles and should include newer information.

Macrophage elastase (MMP-12): a pro-inflammatory mediator?

As many metalloproteinases (MMPs), macrophage elastase (MMP-12) is able to degrade extracellular matrix components such as elastin and is involved in tissue remodeling processes. Studies using animal models of acute and chronic pulmonary inflammatory diseases, such as pulmonary fibrosis and chronic obstrutive pulmonary disease (COPD), have given evidences that MMP-12 is an important mediator of the pathogenesis of these diseases. However, as very few data regarding the direct involvement of MMP-12 in inflammatory process in the airways were available, we have instilled a recombinant form of human MMP-12 (rhMMP-12) in mouse airways. Hence, we have demonstrated that this instillation induced a severe inflammatory cell recruitment characterized by an early accumulation of neutrophils correlated with an increase in proinflammatory cytokines and in gelatinases and then by a relatively stable recruitment of macrophages in the lungs over a period of ten days. Another recent study suggests that resident alveolar macrophages and recruited neutrophils are not involved in the delayed macrophage recruitment. However, epithelial cells could be one of the main targets of rhMMP-12 in our model. We have also reported that a corticoid, dexamethasone, phosphodiesterase 4 inhibitor, rolipram and a non-selective MMP inhibitor, marimastat could reverse some of these inflammatory events. These data indicate that our rhMMP-12 model could mimic some of the inflammatory features observed in COPD patients and could be used for the pharmacological evaluation of new anti-inflammatory treatment. In this review, data demonstrating the involvement of MMP-12 in the pathogenesis of pulmonary fibrosis and COPD as well as our data showing a pro-inflammatory role for MMP-12 in mouse airways will be summarized.

Role of protease-activated receptor-2 in inflammation, and its possible implications as a putative mediator of periodontitis

Proteinase-activated receptor-2 (PAR2) belongs to a novel subfamily of G-protein-coupled receptors with seven-transmembrane domains. This receptor is widely distributed throughout the body and seems to be importantly involved in inflammatory processes. PAR2 can be activated by serine proteases such as trypsin, mast cell tryptase, and bacterial proteases, such as gingipain produced by Porphyromonas gingivalis. This review describes the current stage of knowledge of the possible mechanisms that link PAR2 activation with periodontal disease, and proposes future therapeutic strategies to modulate the host response in the treatment of periodontitis.

Electrocatalytic oxidation of beta-dicarbonyl compounds using ceric methanesulphonate as mediator

beta-dicarbonyl compounds were oxidized electrocatalytically, with fragmentation and loss of "ch2", using ceric methanesulphonate as a mediator. 2,4-pentanedione yields acetic acid (90%), methyl acetoacetate yields acetic acid (84%) plus methanol and dimethyl malonate yields methanol (64%). For 1,3-diphenyl-1,3-propanedione and 1,3-cyclohexanedione, benzoic acid (61% yield) and glutaric acid (75% yield) were obtained, respectively. Methyl cyanoacetate and malononitrile were inert.

A feature-based object-oriented expert system to model and support product design

In this paper a computer program to model and support product design is presented. The product is represented through a hierarchical structure that allows the user to navigate across the product’s components, and it aims at facilitating each step of the detail design process. A graphical interface was also developed, which shows visually to the user the contents of the product structure. Features are used as building blocks for the parts that compose the product, and object-oriented methodology was used as a means to implement the product structure. Finally, an expert system was also implemented, whose knowledge base rules help the user design a product that meets design and manufacturing requirements.

Amplification of 9q34 in childhood adrenocortical tumors: a specific feature unrelated to ethnic origin or living conditions

Adrenocortical tumors (ACT) in children under 15 years of age exhibit some clinical and biological features distinct from ACT in adults. Cell proliferation, hypertrophy and cell death in adrenal cortex during the last months of gestation and the immediate postnatal period seem to be critical for the origin of ACT in children. Studies with large numbers of patients with childhood ACT have indicated a median age at diagnosis of about 4 years. In our institution, the median age was 3 years and 5 months, while the median age for first signs and symptoms was 2 years and 5 months (N = 72). Using the comparative genomic hybridization technique, we have reported a high frequency of 9q34 amplification in adenomas and carcinomas. This finding has been confirmed more recently by investigators in England. The lower socioeconomic status, the distinctive ethnic groups and all the regional differences in Southern Brazil in relation to patients in England indicate that these differences are not important to determine 9q34 amplification. Candidate amplified genes mapped to this locus are currently being investigated and Southern blot results obtained so far have discarded amplification of the abl oncogene. Amplification of 9q34 has not been found to be related to tumor size, staging, or malignant histopathological features, nor does it seem to be responsible for the higher incidence of ACT observed in Southern Brazil, but could be related to an ACT from embryonic origin.

Operant serial feature-positive conditional discrimination with composite features and different topography responses

In a serial feature-positive conditional discrimination procedure the properties of a target stimulus A are defined by the presence or not of a feature stimulus X preceding it. In the present experiment, composite features preceded targets associated with two different topography operant responses (right and left bar pressing); matching and non-matching-to-sample arrangements were also used. Five water-deprived Wistar rats were trained in 6 different trials: X-R®Ar and X-L®Al, in which X and A were same modality visual stimuli and the reinforcement was contingent to pressing either the right (r) or left (l) bar that had the light on during the feature (matching-to-sample); Y-R®Bl and Y-L®Br, in which Y and B were same modality auditory stimuli and the reinforcement was contingent to pressing the bar that had the light off during the feature (non-matching-to-sample); A- and B- alone. After 100 training sessions, the animals were submitted to transfer tests with the targets used plus a new one (auditory click). Average percentages of stimuli with a response were measured. Acquisition occurred completely only for Y-L®Br+; however, complex associations were established along training. Transfer was not complete during the tests since concurrent effects of extinction and response generalization also occurred. Results suggest the use of both simple conditioning and configurational strategies, favoring the most recent theories of conditional discrimination learning. The implications of the use of complex arrangements for discussing these theories are considered.

High mobility group box 1 as a mediator of endotoxin administration after hemorrhagic shock-primed lung injury

High mobility group box 1 (HMGB1) was discovered as a novel late-acting cytokine that contributes to acute lung injury (ALI). However, the contribution of HMGB1 to two-hit-induced ALI has not been investigated. To examine the participation of HMGB1 in the pathogenesis of ALI caused by the two-hit hypothesis, endotoxin was injected intratracheally in a hemorrhagic shock-primed ALI mouse model. Concentrations of HMGB1 in the lung of the shock group were markedly increased at 16 h (1.63 ± 0.05, compared to the control group: 1.02 ± 0.03; P < 0.05), with the highest concentration being observed at 24 h. In the sham/lipopolysaccharide group, lung HMGB1 concentrations were found to be markedly increased at 24 h (1.98 ± 0.08, compared to the control group: 1.07 ± 0.03; P < 0.05). Administration of lipopolysaccharide to the hemorrhagic shock group resulted in a notable HMGB1 increase by 4 h, with a further increase by 16 h. Intratracheal lipopolysaccharide injection after hemorrhagic shock resulted in the highest lung leak at 16 h (2.68 ± 0.08, compared to the control group: 1.05 ± 0.04; P < 0.05). Compared to the hemorrhagic shock/lipopolysaccharide mice, blockade of HMGB1 at the same time as lipopolysaccharide injection prevented significantly pulmonary tumor necrosis factor-alpha, interleukin-1beta and myeloperoxidase. Lung leak was also markedly reduced at 16 h; blockade of HMGB1 24 h after lipopolysaccharide injection failed to alter lung leak or myeloperoxidase at 48 h. Our observations suggest that HMGB1 plays a key role as a late mediator when lipopolysaccharide is injected after hemorrhagic shock-primed ALI and the kinetics of its release differs from that of one-hit ALI. The therapeutic window to suppress HMGB1 activity should not be delayed to 24 h after the disease onset.

TNNI3K is a novel mediator of myofilament function and phosphorylates cardiac troponin I

The phosphorylation of cardiac troponin I (cTnI) plays an important role in the contractile dysfunction associated with heart failure. Human cardiac troponin I-interacting kinase (TNNI3K) is a novel cardiac-specific functional kinase that can bind to cTnI in a yeast two-hybrid screen. The purpose of this study was to investigate whether TNNI3K can phosphorylate cTnI at specific sites and to examine whether the phosphorylation of cTnI caused by TNNI3K can regulate cardiac myofilament contractile function. Co-immunoprecipitation was performed to confirm that TNNI3K could interact with cTnI. Kinase assays further indicated that TNNI3K did not phosphorylate cTnI at Ser23/24 and Ser44, but directly phosphorylated Ser43 and Thr143 in vitro. The results obtained for adult rat cardiomyocytes also indicated that enhanced phosphorylation of cTnI at Ser43 and Thr143 correlated with rTNNI3K (rat TNNI3K) overexpression, and phosphorylation was reduced when rTNNI3K was knocked down. To determine the contractile function modulated by TNNI3K-mediated phosphorylation of cTnI, cardiomyocyte contraction was studied in adult rat ventricular myocytes. The contraction of cardiomyocytes increased with rTNNI3K overexpression and decreased with rTNNI3K knockdown. We conclude that TNNI3K may be a novel mediator of cTnI phosphorylation and contribute to the regulation of cardiac myofilament contraction function.

ANTECEDENTS AND CONSEQUENCES OF HOUSEHOLD FINANCIAL MANAGEMENT IN BRAZILIAN LOWER-MIDDLE-CLASS

Through two complementary and exploratory studies – one qualitative and one quantitative – this research aims to understand the ways in which lower-middle-class families in Brazil manage their household finances. The study proposes an integrated framework that brings together various previously disconnected theoretical fragments. Based on a survey with a sample of 165 lower-middle-class female consumers of a retail company in São Paulo, we explored and tested, via a quantitative study, how antecedents such as personal characteristics affect the financial management process, as well as its consequences, either negatively as defaults or positively as savings. The model calibration and analysis were derived from a series of regression analyses. The results revealed the mediator role that financial management plays in the relationship between personal characteristics and defaults and savings. Compared to previous studies with consumers of more affluent countries, we identified peculiar findings among Brazilian lower-middle-class consumers: inadequate attention to control, weak or no focus on short- or long-range planning, widespread absence of budget surplus, and influence of critical events on episodes of default.

HIV infection and AIDS in a small municipality in Southeast Brazil

OBJECTIVE: Studies on the aspects of HIV infection in small Brazilian municipalities are invaluable to appropriately design control strategies, better allocate resources, and improve health care services. The objective of the study was to assess the clinical and epidemiological aspects of HIV infection in a small municipality. METHODS: A descriptive study was carried out in Miracema, a small municipality in the northwestern area of the state of Rio de Janeiro, Brazil, between July 1999 and December 2003. All HIV-infected adult patients followed up at the local HIV/AIDS Program were included. Clinical and epidemiologic characteristics were prospectively assessed through standardized questionnaires. RESULTS: A total of 65 adult patients who attended the local HIV/AIDS Program were analyzed. Most (34) were women (male to female ratio: 0.9). An absolute predominance of patients who were born in Miracema or neighboring municipalities (94%), lived in Miracema (90.7%), were single (70.8%), attributed the acquisition of HIV infection to unprotected heterosexual intercourse (72.3%) and had a past history of snorting cocaine (27.7) was found Central nervous system disorders (including five cases of cryptococcal meningitis) and acute pulmonary pneumocystosis-like respiratory failure were major causes of morbidity. Most patients (56.9%) were at presented in advanced stages of HIV infection. CONCLUSIONS: The predominance of patients on advanced stages of HIV infection suggest the existence of a large pool of undiagnosed cases in the community. A major feature of the cohort was an inverted male to female ratio. Further investigations over a broader geographic area are urgently needed for better understanding the clinical and epidemiological characteristics of HIV infection in small Brazilian municipalities and rural areas.

Association between social capital and self-perception of health in Brazilian adults

OBJECTIVE To investigate the association between social capital and social capital and self-perception of health based on examining the influence of health-related behaviors as possible mediators of this relationship.METHODS A cross-sectional study was used with 1,081 subjects, which is representative of the population of individuals aged 40 years or more in a medium-sized city in Southern Brazil. The subjects who perceived their health as fine, bad or very bad were considered to have a negative self-perception of their health. The social capital indicators were: number of friends, people from whom they could borrow money from when needed; the extent of trust in community members; whether or not members of the community helped each other; community safety; and extent of participation in community activities. The behaviors were: physical activity during leisure time, fruits and vegetable consumption, tobacco use and alcohol abuse. The odds ratios (OR) and confidence intervals (CI) 95% were calculated by binary logistic regression. The significance of mediation was verified using the Sobel test.RESULTS Following adjustment for demographic and clinical variables, subjects with fewer friends (OR = 1.39, 95%CI 1.08;1.80), those who perceived less frequently help from people in the neighborhood (OR = 1.30, 95%CI 1.01;1.68), who saw the violent neighborhood (OR = 1.33, 95%CI 1.01;1.74) and who had not participated in any community activity (OR = 1.39, 95%CI 1.07;1.80) had more negative self-perception of their health. Physical activity during leisure time was a significant mediator in the relationship between all social capital indicators (except for the borrowed money variable) and self-perceived health. Fruit and vegetable consumption was a significant mediator of the relationship between the extent of participation in community activities and self-perceived health. Tobacco use and alcohol abuse did not seem to have a mediating role in any relationship.CONCLUSIONS Lifestyle seems to only partially explain the relationship between social capital and self-perceived health. Among the investigated behaviors, physical activity during leisure time is what seems to have the most important role as a mediator of this relationship.

Religiousness and health-related quality of life of older adults

OBJECTIVE To examine whether religiousness mediates the relationship between sociodemographic factors, multimorbidity and health-related quality of life of older adults.METHODS This population-based cross-sectional study is part of the Survey on Health, Well-Being, and Aging (SABE). The sample was composed by 911 older adults from Sao Paulo, SP, Southeastern Brazil. Structural equation modeling was performed to assess the mediator effect of religiousness on the relationship between selected variables and health-related quality of life of older adults, with models for men and women. The independent variables were: age, education, family functioning and multimorbidity. The outcome variable was health-related quality of life of older adults, measured by SF-12 (physical and mental components). The mediator variables were organizational, non-organizational and intrinsic religiousness. Cronbach’s alpha values were: physical component = 0.85; mental component = 0.80; intrinsic religiousness = 0.89 and family APGAR (Adaptability, Partnership, Growth, Affection, and Resolve) = 0.91.RESULTS Higher levels of organizational and intrinsic religiousness were associated with better physical and mental components. Higher education, better family functioning and fewer diseases contributed directly to improved performance in physical and mental components, regardless of religiousness. For women, organizational religiousness mediated the relationship between age and physical (β = 2.401, p < 0.01) and mental (β = 1.663, p < 0.01) components. For men, intrinsic religiousness mediated the relationship between education and mental component (β = 7.158, p < 0.01).CONCLUSIONS Organizational and intrinsic religiousness had a beneficial effect on the relationship between age, education and health-related quality of life of these older adults.