Induction of neutralizing antibodies in mice immunized with an amino-terminal polypeptide of Streptococcus mutans P1 protein produced by a recombinant Bacillus subtilis strain

The oral pathogen Streptococcus mutans expresses a surface protein, P1, which interacts with the salivary pellicle on the tooth surface or with fluid-phase saliva, resulting in bacterial adhesion or aggregation, respectively. P1 is a target of protective immunity. Its N-terminal region has been associated with adhesion and aggregation functions and contains epitopes recognized by efficacious antibodies. In this study, we used Bacillus subtilis, a gram-positive expression host, to produce a recombinant N-terminal polypeptide of P1 (P1(39-512)) derived from the S. mutans strain UA159. Purified P1(39-512) reacted with an anti-full-length P1 antiserum as well as one raised against intact S. mutans cells, indicating preserved antigenicity. Immunization of mice with soluble and heat-denatured P1(39-512) induced antibodies that reacted specifically with native P1 on the surface of S. mutans cells. The anti-P1(39-512) antiserum was as effective at blocking saliva-mediated aggregation of S. mutans cells and better at blocking bacterial adhesion to saliva-coated plastic surfaces compared with the anti-full-length P1 antiserum. In addition, adsorption of the anti-P1 antiserum with P1(39-512) eliminated its ability to block the adhesion of S. mutans cells to abiotic surfaces. The present results indicate that P1(39-512), expressed and purified from a recombinant B. subtilis strain, maintains important immunological features of the native protein and represents an additional tool for the development of anticaries vaccines.

Autolytic Mycobacterium leprae Hsp65 fragments may act as biological markers for autoimmune diseases

Investigating the proteolytic activity of the recombinant Mycobacterium leprae Heat Shock Protein of 65 kDa (rHsp65), chaperonin 2 (cpn2), we observed that it displays high instability. The fragmentation process starts at the C-terminus followed by progressive degradation of the N-terminus, which leads to a stable fragment comprising the middle region of the molecule. Urea was able to prevent autolysis, probably due to its denaturing action, while EDTA increased degradation levels indicating the need for metal ions. Peptides originated from autolysis were purified and analyzed by mass spectrometry, generating a continuous map. Since the bacteria and mammalian Hsp60 are known to be targets of the immune response and have been implicated in autoimmune diseases and chronic inflammation, the in vivo effect of rHsp65 peptides was evaluated in the spontaneous Systemic Lupus Erythematosus (SLE) model developed by the (NZB/NZW)F(1) mouse hybrids, and their individual anti-rHsp65 IgG2a/IgG1 antibody titer ratio was determined. The results showed orientation toward a T(H)1 responsiveness, and the treatment with the rHsp65 peptides diminished the environmental variance of the survival time of treated animals. These results outline the fact that environmental factors may also act through the modified stability expression of Heat Shock Proteins intervening during autoimmune processes. (C) 2011 Elsevier Ltd. All rights reserved.

Association between particulate matter from biomass burning and respiratory diseases in the southern region of the Brazilian Amazon

Objective. To investigate the short-term effects of exposure to particulate matter from biomass burning in the Amazon on the daily demand for outpatient care due to respiratory diseases in children and the elderly. Methods. Epidemiologic study with ecologic time series design. Daily consultation records were obtained from the 14 primary health care clinics in the municipality of Alta Floresta, state of Mato Grosso, in the southern region of the Brazilian Amazon, between January 2004 and December 2005. Information on the daily levels of fine particulate matter was made available by the Brazilian National Institute for Spatial Research. To control for confounding factors ( situations in which a non-causal association between exposure and disease is observed due to a third variable), variables related to time trends, seasonality, temperature, relative humidity, rainfall, and calendar effects ( such as occurrence of holidays and weekends) were included in the model. Poisson regression with generalized additive models was used. Results. A 10 mu g/m(3) increase in the level of exposure to particulate matter was associated with increases of 2.9% and 2.6% in outpatient consultations due to respiratory diseases in children on the 6th and 7th days following exposure. Significant associations were not observed for elderly individuals. Conclusions. The results suggest that the levels of particulate matter from biomass burning in the Amazon are associated with adverse effects on the respiratory health of children.

Mitochondrial ion transport pathways: Role in metabolic diseases

Mitochondria are the central coordinators of energy metabolism and alterations in their function and number have long been associated with metabolic disorders such as obesity, diabetes and hyperlipidemias. Since oxidative phosphorylation requires an electrochemical gradient across the inner mitochondrial membrane, ion channels in this membrane certainly must play an important role in the regulation of energy metabolism. However, in many experimental settings, the relationship between the activity of mitochondrial ion transport and metabolic disorders is still poorly understood. This review briefly summarizes some aspects of mitochondrial H(+) transport (promoted by uncoupling proteins, UCPs). Ca(2+) and K(+) uniporters which may be determinant in metabolic disorders. (C) 2009 Elsevier B.V. All rights reserved.

Global stabilizing feedback law for a problem of biological control of mosquito-borne diseases

The control of the spread of dengue fever by introduction of the intracellular parasitic bacterium Wolbachia in populations of the vector Aedes aegypti, is presently one of the most promising tools for eliminating dengue, in the absence of an efficient vaccine. The success of this operation requires locally careful planning to determine the adequate number of mosquitoes carrying the Wolbachia parasite that need to be introduced into the natural population. The latter are expected to eventually replace the Wolbachia-free population and guarantee permanent protection against the transmission of dengue to human. In this paper, we propose and analyze a model describing the fundamental aspects of the competition between mosquitoes carrying Wolbachia and mosquitoes free of the parasite. We then introduce a simple feedback control law to synthesize an introduction protocol, and prove that the population is guaranteed to converge to a stable equilibrium where the totality of mosquitoes carry Wolbachia. The techniques are based on the theory of monotone control systems, as developed after Angeli and Sontag. Due to bistability, the considered input-output system has multivalued static characteristics, but the existing results are unable to prove almost-global stabilization, and ad hoc analysis has to be conducted.

Associação entre as narrativas em saúde bucal e condições socioeconômico-culturais: a dentição como reflexo da desigualdade social

This anthropological study investigates the lived-experience of oral diseases in the context of poverty in Northeast Brazil. During six months in 2004???, ethnographic interviews, narratives and participant-observation with 31 residents of the low-income community, Dendê, located in Fortaleza, Ceará were conducted and analyzed utilizing a hermeneutic-dialetic method. It is revealed that precarious life conditions make prioritizing caretaking a difficult task. Despite suffering tooth pain, seeking a dentist's care is perceived as "a luxury" not a citzens' right. Difficulties in accessing services and poor quality restorations, favor tooth extractions as the most effective intervention. The deterioration of one's oral health is lamented by community members who seek help from popular clinics, politicians and traditional healers. The experience of dental disease differs according to social class, leaves oral scars of inequity, harms self-esteem and inhibits social inclusion. In this context, "treating" the Teeth of Inequity demands that we deepen our comprehension of the social determinants of health, reduce injustice in the access to quality care, remove demoralizing stigmas and empower the community to confront structural forces which affect its life

Acesso aos serviços odontológicos e incidência de cárie em adolescentes e fatores de risco em município do Nordeste Brasileiro, 2006

The aims of this study were to analyze the access of dental services by child population, to determine the prevalence of dental caries, gingivitis and malocclusion in resident children from the municipal district of Sobral Ceará and to evaluate the incidence of the dental decay in adolescents associated with the factors related to socioeconomic condition, access to health services and self-perception. This study had as main factor the multidisciplinary represented by the participation of health professional (doctors, dentists, nurses) in the development of the survey's initial reference; student from Human Sciences area to apply the structured questionnaire in domiciliary visits; statistics professionals in the orientation of the analysis to be held and family health team (community health agents, dentists and dental clinic assistants) in the scheduling of domiciliary visits and the accomplishment of oral exam. The sample was determined from the domicile record that included children born between 1990 and 1994 to develop the research Children health conditions in the municipal district of Sobral Ceará . The first sample comprised 3425 parents of children from 5 to 9 years old, living in the urban area at the municipal district of Sobral Ceará, aiming at identifying the most important factors associated to the access to dental service. From this sample, 1021 children were selected in a systematic way, for the accomplishment to the epidemiological study of decay, gingivitis and malocclusion. In the study's third phase, in order to arrange the group to be followed, 688 adolescents were examined and interviewed, by means of the active search from the 1021 individuals that had been previously examined. It was observed that 50.9% of the children had access to dental service at least once in a lifetime. Of this total, 65.3% accomplished it during the last year, and 85.4% of these did in public services, what allows to identify the importance of this sector in the access to dental services. It was observed that the factors that most affected the access to dental 129 services were related to socioeconomic condition, such as the access to health plan, the possession of toothbrush, garbage collecting, mother s schooling, sewerage treatment and malnutrition. In relation to oral diseases, an increase in the DMF-T index according the age was observed, from 0.10 in five years old to 1.66 in the nine years old, while with the dmf-t index, the inverse happened, since the index decreased from 3.59 in five years old to 2.69 in nine years old. In relation to gingivitis, an average 32.7% of the children presented gum bleeding. In what concerns malocclusion, it was observed that 60.3% of the children didn't present any problem, 30.17% had light malocclusion and 9.5% severe malocclusion. The average incidence of dental caries was 1.86 teeth per youngster. Among the studied variables, tooth pain in the last six months, mother's income and school snack, adjusted by the perception about the need of treatment, the mother's schooling and the dentist's appointment at least once in a lifetime, were the variables that presented positive relationship with the high incidence of dental caries on this population by logistic regression. Variables of socioeconomic nature, related to the access to health services and behavior and biological variables presented a relationship with the high caries incidence. The study point out to the need of developing health actions in a humanized way, by an oral health team effectively bound to the population's interest, with the great objective to provide, with the public health services managers, adequate conditions to improve oral health

Chronic Diseases: Chronic Diseases and Development 2 Health, agricultural, and economic effects of adoption of healthy diet recommendations

Transition to diets that are high in saturated fat and sugar has caused a global public health concern as the pattern of food consumption is a mayor modifiable risk factor for chronic non-communicable diseases Although agri food systems are intimately associated with this transition, agriculture and health sectors are largely disconnected in their priorities policy, and analysis with neither side considering the complex inter relation between agri trade patterns of food consumption health, and development We show the importance of connection of these perspectives through estimation of the effect of adopting a healthy diet on population health, agricultural production trade the economy and livelihoods, with a computable general equilibrium approach on the basis of case studies from the UK and Brazil we suggest that benefits of a healthy diet policy will vary substantially between different populations, not only because of population dietary intake but also because of agricultural production trade and other economic factors

Coenzyme Q(10) and its effects in the treatment of neurodegenerative diseases

According to clinical and pre-clinical studies, oxidative stress and its consequences may be the cause or, at least, a contributing factor, to a large number of neurodegenerative diseases. These diseases include common and debilitating disorders, characterized by progressive and irreversible loss of neurons in specific regions of the brain. The most common neurodegenerative diseases are Parkinson's disease, Huntington's disease, Alzheimer's disease and amyotrophic lateral sclerosis. Coenzyme Q(10) (CoQ(10)) has been extensively studied since its discovery in 1957. It is a component of the electron transportation chain and participates in aerobic cellular respiration, generating energy in the form of adenosine triphosphate (ATP). The property of CoQ(10) to act as an antioxidant or a pro-oxidant, suggests that it also plays an important role in the modulation of redox cellular status under physiological and pathological conditions, also performing a role in the ageing process. In several animal models of neurodegenerative diseases, CoQ(10) has shown beneficial effects in reducing disease progression. However, further studies are needed to assess the outcome and effectiveness of CoQ(10) before exposing patients to unnecessary health risks at significant costs.

Prodrugs for the treatment of neglected diseases

Recently, World Health Organization ( WHO) and Medicins San Frontieres (MSF) proposed a classification of diseases as global, neglected and extremely neglected. Global diseases, such as cancer, cardiovascular and mental (CNS) diseases represent the targets of the majority of the R&D efforts of pharmaceutical companies. Neglected diseases affect millions of people in the world yet existing drug therapy is limited and often inappropriate. Furthermore, extremely neglected diseases affect people living under miserable conditions who barely have access to the bare necessities for survival. Most of these diseases are excluded from the goals of the R&D programs in the pharmaceutical industry and therefore fall outside the pharmaceutical market. About 14 million people, mainly in developing countries, die each year from infectious diseases. From 1975 to 1999, 1393 new drugs were approved yet only 1% were for the treatment of neglected diseases [ 3]. These numbers have not changed until now, so in those countries there is an urgent need for the design and synthesis of new drugs and in this area the prodrug approach is a very interesting field. It provides, among other effects, activity improvements and toxicity decreases for current and new drugs, improving market availability. It is worth noting that it is essential in drug design to save time and money, and prodrug approaches can be considered of high interest in this respect. The present review covers 20 years of research on the design of prodrugs for the treatment of neglected and extremely neglected diseases such as Chagas' disease ( American trypanosomiasis), sleeping sickness ( African trypanosomiasis), malaria, sickle cell disease, tuberculosis, leishmaniasis and schistosomiasis.

Sistemas de liberação de fármaco intrabolsa periodontal

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Prevalência e susceptibilidade antimicrobiana de Staphylococcusspp. em quadros de saúde e doença periodontal

The aim of this study was determine the prevalence and antimicrobial susceptibility of Staphylococcus spp. from patients with periodontal disease and periodontally healthy, correlate them with factors to host, local environment and traits of the diseases. To this, thirty adults from 19 to 55 years old were selected. They had not periodontal treatment and no antibiotic or antimicrobial was administered during three previous months. From these individuals, sites periodontally healthy, with chronic gingivitis and/or periodontitis were analyzed. Eighteen subgingival dental biofilm samples were collected through sterile paper points being six from each tooth randomly selected, representing conditions mentioned. They were transported to Oral Microbiology laboratory, plated onto Mannitol Salt Agar (MSA) and incubated at 370C in air for 48 h. Staphylococcus spp. were identified by colonial morphology, Gram stain, catalase reaction, susceptibility to bacitracin and coagulase activity. After identification, strains were submitted to the antibiotic susceptibility test with 12 antimicrobials, based on Kirby-Bauer technique. To establish the relation between coagulase-negative Staphylococcus (CSN) presence and their infection levels and host factors, local environment and traits of diseases were used Chi-square, Mann-Whitney and Kruskal-Wallis tests to a confidence level of 95%. 86,7% subjects harbored CSN in 11,7% periodontal sites. These prevalence were 12,1% in healthy sites, 11,7% in chronic gingivitis, 13,5% in slight chronic periodontitis, 6,75% in moderate chronic periodontitis and in sites with advance chronic periodontitis was not isolated CSN, without difference among them (p = 0,672). There was no significant difference to presence and infection levels of CSN as related to host factors, local environm ent and traits of the diseases. Amongst the 74 samples of CSN isolated, the biggest resistance was observed to penicillin (55,4%), erythromycin (32,4%), tetracycline (12,16%) and clindamycin (9,4%). 5,3% of the isolates were resistant to oxacilin and methicillin. No resistance was observed to ciprofloxacin, rifampicin and vancomycin. It was concluded that staphylococci are found in low numbers in healthy or sick periodontal sites in a similar ratio. However, a trend was observed to a reduction in staphylococci occurrence toward more advanced stages of the disease. This low prevalence was not related to any variables analyzed. Susceptibility profile to antibiotics demonstrates a raised resistance to penicillin and a low one to methicillin. To erythromycin, tetracycline and clindamycin was observed a significant resistance

Avaliação clínica longitudinal do periodonto de dentes pilares e não pilares de próteses parciais removíveis

The literature has shown a relation between periodontics and the removable partial denture (RPD), with progressive destruction observed in the support structures. The aim of this study was to clinically assess periodontal condition in users of removal partial denture (RPD), and compare right abutments teeth, indirect abutments and controls before installation and after 1 year, in addition to comparing tooth-supported and tooth mucosa-supported abutments. A total of 50 patients, 32 women and 18 men, mean age of 45 years, took part in the study. The patients were examined by a single examiner at prosthesis installation and after 3, 6, 9 and 12 months. The following were verified at each examination: Probe Depth (PD), Plaque Index (PI), Gingival Index (GI), the amount of Keratinized Mucosa (KM), Gingival Recession (GR) and Dental Mobility (DM); in addition patients received oral hygiene orientation, accompanied by prophylaxis, periodontal scaling and root planing (PSRP), when necessary. Analysis of Variance (ANOVA) with Tukey-Kramer post test was used to assess the dependent variables (PD, PI, KM, GR) of the three groups over time while Friedman s test was used for GI. To assess the outcomes of prosthesis type in the right abutment group, a confidence interval-based analysis was performed. The results showed that the control group was the least compromised in all the variables studied. With respect to development of the groups over time, it was verified that the measures for GR, PD, GI and KM increased from initial examination to 1 year of use in all the groups, but only PI showed a significant increase. There was a non-discriminatory low prevalence of dental mobility. The tooth mucosa-supported prosthesis had significantly higher values for GR, GI and PI and significantly lower ones for KM when compared to tooth-supported. Over time, both types of prostheses showed no significant differences from initial to final examination for the variables GR, PD, KM and GI, with PI significant only for tooth-supported. The results showed that the teeth most involved in RPD design had greater potential of periodontal damage, probably because of greater dental biofilm accumulation. Abutments elements adjacent to the free extremities had less favorable periodontal condition than those adjacent to interpolated spaces, but the use of RPD did not worsen the initial condition