Matrix metalloproteinase 9 gene haplotypes affect left ventricular hypertrophy in hypertensive patients

Background: Matrix metalloproteinases (MMPs) are involved in cardiac remodeling and are encoded by genes showing genetic polymorphisms that have functional implications. We examined whether MMP-9 genetic polymorphisms are associated with hypertension and with left ventricular (LV) remodeling in hypertensive patients. Methods: We studied 173 hypertensive patients and 137 age, race and gender matched healthy controls. Heart echocardiography was performed in all patients and the following MMP-9 genetic polymorphisms were analyzed: C-(1562)T (rs3918242). -90 (CA)(14-24) (rs2234681) and Q279R (rs17576). Haplo.stats analysis was used to assess whether MMP-9 haplotypes are associated with hypertension. Linear regression analysis was performed to assess whether MMP-9 haplotypes affect LV mass index (LVMI) and other echocardiography parameters. Results: MMP-9 90 (CA)14-24 ""HH"" genotype (H allele defined by number of CA repeats >= 21) was associated with hypertension (P = 0.0085; OR = 2.321, 95% confidence interval = 1.250 to 4.309). While one MMP-9 haplotype (""C. H, Q"") protects against LVMI and end-diastolic diameter increases due to remodeling (P = 0.0490 and P = 0.0367), another MMP-9 haplotype apparently has detrimental effects over both parameters in hypertensive patients (""T, H. Q"", P = 0.0015 and P = 0.0057. respectively). Conclusion: Genetic polymorphisms in MMP-9 gene may modify the susceptibility of hypertensive patients to LV remodeling. Further studies are necessary to examine whether these polymorphisms affect clinical events in hypertensive patients. (C) 2010 Elsevier B.V. All rights reserved.

The Stability of the Blood Oxygenation Level-Dependent Functional MRI Response to Motor Tasks Is Altered in Patients With Chronic Ischemic Stroke

Background and Purpose-Functional MRI is a powerful tool to investigate recovery of brain function in patients with stroke. An inherent assumption in functional MRI data analysis is that the blood oxygenation level-dependent (BOLD) signal is stable over the course of the examination. In this study, we evaluated the validity of such assumption in patients with chronic stroke. Methods-Fifteen patients performed a simple motor task with repeated epochs using the paretic and the unaffected hand in separate runs. The corresponding BOLD signal time courses were extracted from the primary and supplementary motor areas of both hemispheres. Statistical maps were obtained by the conventional General Linear Model and by a parametric General Linear Model. Results-Stable BOLD amplitude was observed when the task was executed with the unaffected hand. Conversely, the BOLD signal amplitude in both primary and supplementary motor areas was progressively attenuated in every patient when the task was executed with the paretic hand. The conventional General Linear Model analysis failed to detect brain activation during movement of the paretic hand. However, the proposed parametric General Linear Model corrected the misdetection problem and showed robust activation in both primary and supplementary motor areas. Conclusions-The use of data analysis tools that are built on the premise of a stable BOLD signal may lead to misdetection of functional regions and underestimation of brain activity in patients with stroke. The present data urge the use of caution when relying on the BOLD response as a marker of brain reorganization in patients with stroke. (Stroke. 2010; 41:1921-1926.)

Relationship among eccentric hip and knee torques, symptom severity and functional capacity in females with patellofemoral pain syndrome

Objective: To determine the relationships between eccentric hip and knee torques, symptom severity and functional capacity in females with patellofemoral pain syndrome (PFPS). Design: Within-subject correlational study. Setting: University biomechanics laboratory. Participants: 10 females diagnosed with PFPS. Main outcome measures: Eccentric strength of the hip abductors and lateral rotators, and knee extensors were assessed using an isokinetic dynamometer. A 10-cm visual analog scale was used to determine usual knee pain in the last week. The Anterior Knee Pain Scale (AKPS) was used to determine the functional capacity of the patients. Results: The study found that the greater the eccentric knee extensor and hip lateral rotator torques, the higher the functional capacity of the patients (p = 0.02, r = 0.72; p = 0.02, r = 0.72). It was also shown that the greater hip lateral rotator torque, the less the usual pain reported in the last week (p = 0.004, r = -0.84). Despite the lack of statistical significance (p = 0.11), it was also found a modest negative relationship between the eccentric knee extensor torque and the usual pain reported in the last week (r = -0.56) that was considered clinically meaningful (d = 1.4). Conclusions: This study showed that eccentric knee extensor and hip lateral rotator torques were associated with functional capacity and pain level in females with PFPS. Further investigations should be carried out to verify the effects of an intervention program focused on the eccentric action of these muscles with respect to the symptoms in patients with PFPS. (C) 2011 Elsevier Ltd. All rights reserved.

Stability improvement of the fatty acid binding protein Sm14 from S. mansoni by Cys replacement: Structural and functional characterization of a vaccine candidate

The Schistosoma mansoni fatty acid binding protein (FABP), SmA, is a vaccine candidate against, S. mansoni and F hepatica. Previously, we demonstrated the importance of a correct fold to achieve protection in immunized animals after cercariae challenge [[10]. C.R.R. Ramos, R.C.R. Figueredo, T.A. Pertinhez, M.M. Vilar, A.L.T.O. Nascimento, M. Tendler, I. Raw, A. Spisni, P.L. Ho, Gene structure and M20T polymorphism of the Schistosoma mansoni Sm14 fatty acid-binding protein: structural, functional and immunoprotection analysis. J. Biol. Chem. 278 (2003) 12745-12751]. Here we show that the reduction of vaccine efficacy over time is due to protein dimerization and subsequent aggregation. We produced the mutants Sm14-M20(C62S) and Sm14M20(C62V) that, as expected, did not dimerize in SDS-PAGE. Molecular dynamics calculations and unfolding experiments highlighted a higher structural stability of these mutants with respect to the wild-type. In addition, we found that the mutated proteins, after thermal denaturation, refolded to their active native molecular architecture as proved by the recovery of the fatty acid binding ability. Sm14-M20(C62V) turned out to be the more stable form over time, providing the basis to determine the first 3D solution structure of a Sm14 protein in its apo-form. Overall, Sm14-M20(C62V) possesses an improved structural stability over time, an essential feature to preserve its immunization capability and, in experimentally immunized animals, it exhibits a protection effect against S. mansoni cercariae infections comparable to the one obtained with the wild-type protein. These facts indicate this protein as a good lead molecule for large-scale production and for developing an effective Sm14 based anti-helminthes vaccine. (C) 2008 Elsevier B.V. All rights reserved.

Protease activity and the ultrastructure of broiler chicken PSE (pale, soft, exudative) meat

The biological cause of broiler PSE meat seems to be an excessive release of Ca(2+), promoted by a genetic mutation of ryanodine receptors located in the sarcoplasmic reticulum of skeletal muscle cells. Excessive Ca(2+), associated with protein denaturation in meat, enhances protease activity and influences the functional properties of PSE meat. Twenty-four-hour post-mortem Pectoralis major m. samples exhibited lower values for pH, water-holding capacity, and shear force than did control samples, in contrast to colour (L*) and cooking loss values. Protease activity, measured as myofibril fragmentation index, presented higher values in PSE meat than in control samples. Ultrastructural examination revealed shrinking and depolymerisation of myofilaments and Z-lines disorganisation within the sarcomere in PSE meat. Intense calpain activity was also observed, indicating that the process may initiate at the filaments, because of protein denaturation, and spread through Z-lines, resulting in the collapse of the sarcomere structure. (C) 2009 Elsevier Ltd. All rights reserved.

Bispectral index in dogs at three intravenous infusion rates of propofol

Objective To establish the correlation between the bispectral index (BIS) and different rates of infusion of propofol in dogs. Study design Prospective experimental trial. Animals Eight adult dogs weighing 6-20 kg. Methods Eight animals underwent three treatments at intervals of 20 days. Propofol was used for induction of anesthesia (10 mg kg(-1) IV), followed by a continuous rate infusion (CRI) at 0.2 mg kg(-1) minute(-1) (P2), 0.4 mg kg(-1) minute(-1) (P4) or 0.8 mg kg(-1) minute(-1) (P8) for 55 minutes. The BIS values were measured at 10, 20, 30, 40, and 50 minutes (T10, T20, T30, T40, and T50, respectively) after the CRI of propofol was started. Numeric data were submitted to analysis of variance followed by Tukey test (p < 0.05). Results The BIS differed significantly among groups at T40, when P8 was lower than P2 and P4. At T50, P8 was lower than P2. The electromyographic activity (EMG) in P2 and P4 was higher than P8 at T40 and T50. Conclusion An increase in propofol infusion rates decreases the BIS values and EMG.

Absence of functional TLR4 impairs response of macrophages after Candida albicans infection

Candida albicans is recognized by phagocytic cells through a set of recognition receptors patterns. Recently, we showed the importance of TLR2 in the regulation of neutrophil survival after C. albicans infection. In the present work, we analyzed the involvement of TLR4 in the recognition of C. albicans by neutrophils and macrophages. Our results show that the absence of functional TLR4 resulted in lower chemotaxis of neutrophils to the site of infection, lower levels of TNF-alpha, CXCL1 and nitric oxide, and dissemination and persistence of the pathogen in lymph nodes and spleen. In vitro, the phagocytic activity, nitric oxide production and myeloperoxidase activity, CXCL1, IL-1 beta production by neutrophils from TLR4-defective mice were not changed. In contrast, macrophages from TLR4-defective mice demonstrated lower phagocytosis and lower levels of CXCL1, IL-1 beta and TNF-alpha. Together, these data demonstrate that TLR4 signals are important for the recognition of C. albicans by macrophages and their absence allows persistence of the infection.

The broad effects of the functional IL-10 promoter-592 polymorphism: modulation of IL-10, TIMP-3, and OPG expression and their association with periodontal disease outcome

Periodontal diseases are infectious diseases, in which periodontopathogens trigger chronic inflammatory and immune responses that lead to tissue destruction. It occurs through the generation of metalloproteinases and the activation of bone resorption mechanisms. Anti-inflammatory cytokines such as IL-10 seem to attenuate periodontal tissue destruction through the induction of tissue inhibitors of metalloproteinases (TIMPs) and the inhibitor of osteoclastogenesis osteoprotegerin (OPG). A high individual variation in levels of IL-10 mRNA is verified in periodontitis patients, which is possibly determined by genetic polymorphisms. In this study, the IL-10 promoter -592C/A single nucleotide polymorphism ( SNP), which is associated with a decrease in IL-10 production, was analyzed by RFLP in 116 chronic periodontitis (CP) patients and 173 control (C) subjects, and the IL-10, TIMPs, and OPG mRNA expression levels in diseased gingival tissues were determined by real-time-PCR. The IL-10-592 SNP CA (P=0.0012/OR=2.4/CI:1.4-4.1), AA (P=0.0458/OR=2.3/CI:1.1-4.9), and CA+AA (P=0.0006/OR=2.4/CI: 1.4-3.4) genotypes and the allele A (P=0.0036/OR=1.7/CI:1.2-2.4) were found to be significantly more prevalent in the CP group when compared with control subjects. Both CA and AA genotypes were associated with lower levels of IL-10, TIMP-3, and OPG mRNA expression in diseased periodontal tissues and were also associated with disease severity as mean pocket depth. Taken together, the results presented here demonstrate that IL10-592 SNP is functional in CP, being associated with lower levels of IL-10 mRNA expression, which is supposed to consequently decrease the expression of the downstream genes TIMP-3 and OPG, and influence periodontal disease outcome. J. Leukoc. Biol. 84: 1565-1573; 2008.

Prevalence of dental wear among 12-year-old Brazilian adolescents using a modification of the tooth wear index

Objective. This study investigated the prevalence of dental wear in 12-year-old adolescents using a modification of the tooth wear index (TWI). The modifications were proposed in order to fit with the World Health Organization standard, thus allowing application of the index in broad epidemiological surveys. Study design: An epidemiological cross-sectional survey was performed by trained, calibrated examiners, using a modified version of the TWI. Methods: Urban elementary schools were chosen because they provide a fair representation of the city`s population in terms of socio-economic status. The sample included 295 adolescents, selected randomly and systematically. Dental wear was assessed by calibrated examiners (kappa > 0.85), using a modified version of the TWI. This modified version includes a code for teeth restored due to wear, and another code for teeth that cannot be assessed. In addition, it does not differentiate the depth of dentine involvement. Proportions and confidence intervals were used to describe the prevalence of dental wear. Mann-Whitney test was used to detect differences in the degree of dental wear between mates and females. The level of statistical significance was set at 5%. Results: In total, 24,780 dental surfaces were evaluated. Among these surfaces, 73.10% did not present dental wear, 24.10% had incipient lesions, 2.46% had moderate lesions and 0.34% had been restored. No severe lesions were detected. Tooth wear was mainly seen on the occlusal/incisal surfaces (26.55%), involving enamel or enamel-dentine, but not the secondary dentine or pulp. The prevalence of dental wear was 26.90%. Considering the different teeth, wear was present in 53.22% of incisors, 50.51% of canines, 10.17% of premolars and 10.85% of molars. The prevalence of the different degrees of dental wear was similar in mates and females (P > 0.05). Conclusion: The modified TWI seems to bean effective toot for use in broad epidemiological surveys, due to easier calibration and high reproducibility rates. (C) 2008 The Royal Institute of Public Health. Published by Elsevier Ltd. All rights reserved.

Esthetic and functional restoration for an anterior open occlusal relationship with multiple diastemata: A multidisciplinary approach

An anterior open occlusal relationship and diastemata may negatively interfere with the harmony of the smile, often requiring a multidisciplinary intervention. This clinical report presents an integrated orthodontic, periodontal, and restorative solution for an anterior open occlusal relationship associated with multiple diastemata and discusses the most relevant aspects related to Its etiology and treatment planning.

SHED Differentiate into Functional Odontoblasts and Endothelium

Studies on mechanisms underlying the differentiation of dental pulp stem cells are critical for the understanding of the biology of odontogenesis and for dental tissue engineering. Here, we tested the hypothesis that stem cells from exfoliated deciduous teeth (SHED) differentiate into functional odontoblasts and endothelial cells. SHED were seeded in tooth slice/scaffolds and implanted subcutaneously into immunodeficient mice. SHED differentiated into functional odontoblasts that generated tubular dentin, as determined by tetracycline staining and confocal microscopy. These cells also differentiated into vascular endothelial cells, as determined by beta-galactosidase staining of LacZ-tagged SHED. In vitro, vascular endothelial growth factor (VEGF) induced SHED to express VEGFR2, CD31, and VE-Cadherin (markers of endothelium) and to organize into capillary-like sprouts. VEGF induced ERK and AKT phosphorylation (indicative of differentiation), while inhibiting phosphorylation of STAT3 (indicative of `stemness`). Collectively, this work demonstrates that SHED can differentiate into angiogenic endothelial cells and odontoblasts capable of generating tubular dentin.

A comparison of the dental health of Brazilian and Canadian independently living elderly

Objective: To compare the dental status of Brazilian and Canadian elderly populations with respect to socioeconomic and quality of life factors. Materials and methods: A total of 496 adults aged 60-75 years, having four or more teeth, and physically and cognitively suitable for a clinical oral examination were included. Subjects answered questions concerning their lifestyle and completed the Geriatric Oral Health Assessment Index (GOHAI) questionnaire. Results: In all populations, the majority were females, aged between 60 and 65 years and married. Although the Canadian New Immigrant population had lower mean income, they had more remaining teeth (23.04 +/- 6.1), more functional teeth (sound and restored teeth) (14.92 +/- 5.7), more sound teeth (15.40 +/- 7.6), but more carious teeth (2.97 +/- 3.0). The Brazilian population had higher numbers of restored teeth (12.26 +/- 6.8) and fewer remaining teeth (17.80 +/- 7.6). In all populations, females, married and younger (60-65 years old) adults were more likely to retain 20 or more teeth. The mean GOHAI scores were similar for Canadians (40.55 +/- 5.7) and Canadian New Immigrants (39.28 +/- 6.5), but were higher than that among Brazilians (31.97 +/- 8.9). Conclusions: The numbers of remaining teeth were related to greater education and higher income status for Brazilian and Canadian populations. However, Canadian New Immigrants with lower income and education retained more teeth than the other populations.

Improvement of the electrolytic properties of Y2O3-based materials using a crystallographic index

Y2O3 is a c-type rare earth oxide with a fluorite-related structure. This material has been used to refractory because of its high thermal stability and excellent resistance to hydration. In this study, the effective index was suggested in order to improve the electrolytic properties of Y2O3-based oxide. (CexY1-x)(2)O3+delta (x = 0.25 and 0.3) and [LaaSrbCe0.25Y(1-a-b)](2)O3+delta (a = 0.05, 0.1 and 0.15, b = 0, 0.006 and 0.0125) were prepared as the examples with intermediate and high index, respectively. The specimens with high index value such as (La0.15Ce0.25Y0.60)(2)O-3.25 and (La0.1Sr0.0125Ce0.25Y0.6375)(2)O-3.24 consisted of two phases such as c-type and fluorite, although (Ce0.25Y0.75)(2)O-3.25 with intermediate index value had a single phase of c-type rare earth oxide. Microanalysis indicates that a grain in the (La0.1Sr0.0125Ce0.25Y0.6375)(2)O-3.23(7) sintered body consists of c-type and fluorite phases. An interface between c-type and fluorite phases is coherent in a grain. This suggests that this effective index guides the crystal structure in the specimen to fluorite and the examined composition introduces the interface between c-type and fluorite in the microstructure. The electrochemical properties of specimens including Y2O3 were characterized on the basis of the suggested index. The electrical conductivity of Y2O3-based materials increased with an increase of the index. The apparent activation energy of Y2O3-based materials decreased with increasing index. The ionic transport number of oxygen of the specimens was improved by enhancement of the index, confirming validity of the index. The oxide ionic conductive region of (La0.1Sr0.0125Ce0.25Y0.(6375))(2)O-3.23(7) with high effective index extended up to P-O2 = 10(-18) atm at 800 degreesC, although the specimens with low or intermediate index showed p- or n-type semi-conduction in the same P-O2 region at 800 and 1000 degreesC. These results suggest that the interface between c-type and fluorite phases also contributes to improve the electrolytic properties in the grain. It is concluded that the improvement of electrolytic properties in Y2O3-based materials is attributable to the microstructure with interface between two phases in a grain and the fluorite structure guided by the suggested index. (C) 2001 Published by Elsevier Science B.V.

Functional polymorphisms in the promoter of the matrix metalloproteinase-9 (MMP-9) gene are not linked with significant plasma MMP-9 variations in healthy subjects

Background: Matrix metalloproteinase-9 (MMP-9) is involved in the degradation of the extracellular matrix during physiological and pathological processes. Two functional polymorphisms [C(-1562)T and microsatellite (CA)(13-25)] in the promoter region of the MMP-9 gene have been associated with several diseases. The aim of this study was to examine whether these MMP-9 polymorphisms and haplotypes are linked with plasma MMP-9 variations in healthy subjects. Methods: We studied 177 healthy male white volunteers (age range 20-55 years) who were non-smokers and not taking any medication. Genomic DNA was extracted from whole blood and genotypes for the C(-1562)T and the microsatellite (CA)(n) polymorphisms were determined. MMP-9 levels were measured in plasma samples by gelatin zymography. Results: The frequency of the alleles C and T for the C(-1562)T polymorphism were 90% and 10%, respectively. The frequency of the alleles with less than 21 CA repeats Q and with 21 repeats or higher (H) were 47% and 53%, respectively. We found no differences in plasma MMP-9 levels among the genotype groups or among different haplotypes (all p > 0.05). Conclusions: These findings suggest that functional polymorphisms in the promoter of the MMP-9 gene are not linked with significant plasma MMP-9 variations in healthy subjects.

Functional mapping of the periaqueductal gray matter involved in organizing tonic immobility behavior in guinea pigs

Tonic immobility behavior (TI) is an innate response characterized by profound motor inhibition that is exhibited by prey when physical contact with a predator is prolonged and the situation inescapable. The periaqueductal gray matter (PAG) is intimately associated with the somatic and autonomic components of defensive reactions. This study investigated whether the TI response was able to recruit specific functional columns of the PAG by examining c-fos immunolocalization in guinea pigs. In the TI group, the innate response was invoked in animals through inversion and physical contention for at least 15 min. In the control group, the animals were physically manipulated only. Our results demonstrate that the defensive behavior of TI is capable of promoting the expression of Fos protein in different areas of the PAG, with higher levels of staining in the ventrolateral (vI) and lateral (I) columns. In addition, our results demonstrate increased Fos immunoreactivity (FOS-IR) in the dorsal raphe nucleus, the Edinger-Westphal nucleus, the cuneiform nucleus and the superior colliculus. In contrast, there were no significant alterations in the number of FOS-IR cells in the inferior colliculus or the oculomotor nucleus. Analysis of the results suggests that neuronal activation after the TI response differs by functional column of the PAG. (C) 2010 Elsevier B.V. All rights reserved.