Loss of muscle proteins and the consequent weakness has important clinical consequences in diseases such as cancer, diabetes, chronic heart failure, and in aging. In fact, excessive proteolysis causes cachexia, accelerates disease progression, and worsens life expectancy. Muscle atrophy involves a common pattern of transcriptional changes in a small subset of genes named atrophy-related genes or atrogenes. Whether microRNAs play a role in the atrophy program and muscle loss is debated. To understand the involvement of miRNAs in atrophy we performed miRNA expression profiling of mouse muscles under wasting conditions such as fasting, denervation, diabetes, and cancer cachexia. We found that the miRNA signature is peculiar of each catabolic condition. We then focused on denervation and we revealed that changes in transcripts and microRNAs expression did not occur simultaneously but were shifted. Indeed, whereas transcriptional control of the atrophy-related genes peaks at 3 days, changes of miRNA expression maximized at 7 days after denervation. Among the different miRNAs, microRNA-206 and -21 were the most induced in denervated muscles. We characterized their pattern of expression and defined their role in muscle homeostasis. Indeed, in vivo gain and loss of function experiments revealed that miRNA-206 and miRNA-21 were sufficient and required for atrophy program. In silico and in vivo approaches identified transcription factor YY1 and the translational initiator factor eIF4E3 as downstream targets of these miRNAs. Thus miRNAs are important for fine-tuning the atrophy program and their modulation can be a novel potential therapeutic approach to counteract muscle loss and weakness in catabolic conditions.
The objective of this study is to reflect on care for people with terminal illnesses in primary health care. This study is relevant in the current context of demographic and epidemiological transition, in which there is an increase in the aging population and a rise in the prevalence of chronic degenerative diseases. By means of qualitative research with a critical hermeneutic focus, individual interviews were conducted with seven family members, three professionals from the Family Health Strategy and two professionals from the Home Care Program. The analysis established two empirical categories: end of life care from the perception of family members and that of health professionals. The results showed that, despite the humanization discourse, reflected in the prerogative of living the final moments of life with the family, a serious problem in the discontinuity of care is concealed. It was concluded that, despite the efforts, little is achieved in improving the quality of life for those who die from terminal diseases at home in the Unified Health System in municipalities distant from large centers.
Prolonged strenuous exercise is commonly reported to depress oral-respiratory immune status and increase the incidence of upper respiratory symptoms. This novel investigation aimed to determine the salivary antimicrobial responses and hydration status of ultraendurance runners (n = 23) during a 230-km multistage ultramarathon conducted in hot ambient conditions (32-40 °C). Body mass was measured and unstimulated saliva and venous blood samples were taken before and after each stage of the ultramarathon. Ad libitum fluid intake was permitted throughout each race day. Upper respiratory symptoms were monitored during and until 4 weeks after race completion. Samples were analyzed for salivary immunoglobulin A (IgA), lysozyme, ?-amylase, and cortisol, as well as for plasma and saliva osmolality. Mean exercise-induced body mass loss over the 5 stages ranged from 1.3% to 2.4%. Overall mean pre- and post-stage plasma osmolality measurements in the ultraendurance runners were 279 ± 14 mOsmol·kg(-1) and 293 ± 15 mOsmol·kg(-1), respectively. Decreases in saliva flow rate (overall change 22%) and post-stage increases in saliva osmolality (36%) were observed in the ultraendurance runners during the ultramarathon. Reduced salivary IgA (32%) (p < 0.001 vs. pre-stage salivary IgA), enhanced salivary ?-amylase (187%) (p < 0.001 vs. pre-stage salivary ?-amylase), and no change in salivary lysozyme secretion rates were observed in the ultraendurance runners throughout the ultramarathon. Only 1 ultraendurance runner reported upper respiratory symptoms during and 1 month after competition. Observed depressions in salivary IgA secretion rates were offset by favourable increases in salivary ?-amylase and unchanged lysozyme responses in the majority of runners during the competition. Ensuring euhydration throughout a multistage ultramarathon competition in the heat may play a role in protecting the upper respiratory tract.
In Northeast Brazil, large domestic containers used to store water are important breeding sites of Aedes aegypti, the main vector of dengue fever. The objective of this study was to estimate the survival of Betta splendens (Perciformes: Osphronemidae) fish in domestic containers in Fortaleza (Ceará State), as well as its effectiveness in the control of premature A. aegypti stages.
Since the registration of Aedes albopictus in the municipality of Fortaleza in 2005, it has shown rapid dispersion. A study aiming to identify its occurrence areas, breeding sites and associations with Aedes aegypti and other culicids was carried out during 2008.
This study was carried out to evaluate the residual effect of three larvicides under laboratory conditions for 100 days in Aedes aegypti. The larval mortality rate was measured without water renewal or with daily water renewal (80%). With temephos, there was 100% mortality in both groups until the 70th day. In the Bacillus thuringiensis israelensis (Bti)-WDG test, there was no difference during the first 20 days. With Bti-G, without water renewal, mortality was sustained above 90% for up to 35 days. The second experiment (with water renewal) reduced the mortality to below 90% after the first 20 days. When renewed water was provided, the residual effect was significantly lower for all larvicides.
The two fish species Betta splendens (Regan) and Poecilia reticulata (Peters) are known predators of Aedes aegypti (L., 1762) larvae. Both species have been used for biological control in northeastern Brazil. However, the feasibility of these fish for the control of Ae. aegypti larvae in domestic containers may be limited by their survival in chlorinated water, as supplied by the public water system. We exposed fish to three different concentrations of chlorine: 1, 1.5, and 2.0 mg/liter. All B. splendens survived at 1.0 mg/liter chlorine concentration; 72.5 and 39.3% of B. splendens survived chlorine concentrations of 1.5 and 2.0 mg/liter, respectively. In contrast, only 4.4% of P. reticulata survived at a chlorine concentration of 1.0 mg/liter. We conclude that B. splendens may be an appropriate species for biological control of Ae. aegypti in domestic water tanks.
Dengue is a serious disease transmitted by the mosquito Aedes aegypti during blood meal feeding. It is estimated that the dengue virus is transmitted to millions of individuals each year in tropical and subtropical areas. Dengue control strategies have been based on controlling the vector, Ae. aegypti, using insecticide, but the emergence of resistance poses new challenges. The aim of this study was the identification of specific protease inhibitors of the digestive enzymes from Ae. aegypti larvae, which may serve as a prospective alternative biocontrol method. High affinity protein inhibitors were selected by all of the digestive serine proteases of the 4th instar larval midgut, and the specificity of these inhibitors was characterized. These inhibitors were obtained from a phage library displaying variants of HiTI, a trypsin inhibitor from Haematobia irritans, that are mutated in the reactive loop (P1-P4). Based on the selected amino acid sequence pattern, seven HiTI inhibitor variants were cloned, expressed and purified. The results indicate that the HiTI variants named T6 (RGGAV) and T128 (WNEGL) were selected by larval trypsin-like (IC(50) of 1.1 nM) and chymotrypsin-like enzymes (IC(50) of 11.6 nM), respectively. The variants T23 (LLGGL) and T149 (GGVWR) inhibited both larval chymotrypsin-like (IC(50) of 4.2 nM and 29.0 nM, respectively) and elastase-like enzymes (IC(50) of 1.2 nM for both). Specific inhibitors were successfully obtained for the digestive enzymes of Ae. aegypti larvae by phage display. Our data also strongly suggest the presence of elastase-like enzymes in Ae. aegypti larvae. The HiTI variants T6 and T23 are good candidates for the development as a larvicide to control the vector.
This research deals with the potential and limitations of the strengthening of subjects in health management, based on the experience in Fortaleza in the period from 2005 to 2008. The subject is approached from a historical-cultural standpoint, which considers the dialectical interaction between the individual and the collective in deepening human consciousness on the self and the world. Focus groups were conducted with managers linked to Primary Healthcare and secondary data were utilized. An attempt was made to understand the meaning of the narratives constructed using a hermeneutic dialectic approach. Empirical categories were identified and analyzed as well as co-intentionality of change, political and conceptual drives, human management, reduction of hierarchy, fragmentation of work processes and concentration of decision-making power. Reflections arose on three main strategic policies: co-management, humanization, and continuous health education. It was concluded that, despite the persistence of obstacles, in order to improve the quality of healthcare services it is essential to establish a democratic management system through organizational arrangements and participatory methods that enhance integration and commitment of the Unified Health System players (SUS).
The biomedical view sees deafness as a physiological loss of audition and the deaf as individuals with an organic abnormality to be corrected; healthcare interventions support this perception. This study sought to understand deafness from the standpoint of the deaf, in order to identify elements for public policies addressed to them in the context of the ethical dimension of care. The research adopted the qualitative approach (focus groups) and 9 members of a deaf community in Fortaleza (Ceará-Brazil), all fluent in Brazilian Sign Language-LIBRAS, took part. The results show deafness is perceived as a way of being based on day-to-day experiences of visual interaction with nature and society, giving the deaf a different identity in terms of culture (being deaf) and linguistics (LIBRAS). Some public policies for oral training and technological interventions, like cochlear implants, are seen as a setback by the deaf, as it negates their status in the world and involves a loss of identity for the deaf. It is necessary to consider the deaf from a socio-historic, symbolic and cultural standpoint where different discourses co-exist, over and above the physiological dimension.
Rhipicephalus (Boophilus) microplus is an ectoparasite responsible for an important decrease in meat, milk and leather production, caused both by cattle blood loss and by the transmission of anaplasmosis and babesiosis. R. microplus is a rich source of serine protease inhibitors, including the trypsin inhibitors BmTI-A and BmTI-6, the subtilisin inhibitor BmSI, and the recently described thrombin inhibitor, boophilin. Boophilin is a double Kunitz-type thrombin inhibitor, with the unusual ability to form a ternary complex with a second (non-thrombin) serine proteinase molecule. The large-scale expression and purification of boophilin and of its isolated N-terminal (D1) domain in Pichia pastoris, its expression profile, and the effect of RNAi-mediated gene silencing in tick egg production are reported. Full-length boophilin and D1 were expressed at 21 and 37.5mg/L of culture, respectively. Purified boophilin inhibited trypsin (K(i) 0.65 nM), neutrophil elastase (K(i) 21 nM) and bovine thrombin (K(i) 57 pM), while D1 inhibited trypsin and neutrophil elastase (K(i) of 2.0 and 129 nM, respectively), but not thrombin. Boophilin gene silencing using RNAi resulted in 20% reduction in egg weight production, suggesting that the expression of boophilin in this life stage would be important but not vital, probably due to functional overlap with other serine proteinase inhibitors in the midgut of R. microplus. Considering our data, Boophilin could be combining with other antigen in a vaccine production for tick control.
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