Toxicological evaluation of lactose and chitosan delivered by inhalation

These days, inhalation constitutes a promising administration route for many drugs. However, this route exhibits unique limitations, and formulations aimed at pulmonary delivery should include as few as possible additives in order to maintain lung functionality. The purpose of this work was to investigate the safety of lactose and chitosan to the pulmonary tissue when delivered by inhalation. The study was carried out with 18 Wistar rats divided in three groups receiving distilled water, lactose or chitosan. A solution of each excipient was administered by inhalation at a dose of 20 mg. The lungs were excised and processed to determine several biochemical parameters used as toxicity biomarkers. Protein and carbonyl group content, lipid peroxidation, reduced and oxidized glutathione ( GSSG), myeloperoxidase ( MPO), cooper/zinc and manganese superoxide dismutase, catalase, glutathione S-transferase and glutathione peroxidase were determined. Results of myeloperoxidase activity and glutathione disulfide lung concentrations showed a relevant decrease for chitosan group compared to control: 4.67 +/- 2.27 versus 15.10 +/- 7.27 ( P = 0.011) for MPO and 0.89 +/- 0.68 versus 2.02 +/- 0.22 ( P = 0.014) for GSSG. The other parameters did not vary significantly among groups. Lactose and chitosan administered by inhalation failed to show toxic effects to the pulmonary tissue. A protective effect against oxidative stress might even be attributed to chitosan, since some biomarkers had values significantly lower than those observed in the control group when this product was inhaled. Nevertheless, caution must be taken regarding chemical composition and technological processes applied to incorporate these products during drug formulation, in particular for dry powder inhalators

Pit and fissure sealants in dental public health – application criteria and general policy in Finland

<p>Abstract</p> <p>Background</p> <p>Pit and fissure sealants (sealants) are widely used as a non-operative preventive method in public dental health in Finland. Most children under 19 years of age attend the community-organized dental health services free of charge. The aims of this study were to find out to what extent sealants were applied, what the attitudes of dental professionals towards sealant application were, and whether any existing sealant policies could be detected among the health centres or among the respondents in general. The study evaluated changes that had taken place in the policies used during a ten year period (1991–2001).</p> <p>Methods</p> <p>A questionnaire was mailed to each chief dental officer (CDO) of the 265 public dental health centres in Finland, and to a group of general dentists (GDP) applying sealants in these health centres, giving a total of 434 questionnaires with 22 questions. The response rate was 80% (N = 342).</p> <p>Results</p> <p>A majority of the respondents reported to application of sealants on a systematic basis for children with increased caries risk. The criteria for applying sealants and the actual strategies seemed to vary locally between the dentists within the health centres and between the health centres nationwide. The majority of respondents believed sealants had short- and long-term effects. The overall use of sealants decreased towards the end of the ten year period. The health centres (N = 28) choosing criteria to seal over detected or suspected enamel caries lesion had a DMFT value of 1.0 (SD ± 0.49) at age 12 (year 2000) compared to a value of 1.2 (SD ± 0.47) for those health centres (N = 177) applying sealants by alternative criteria (t-test, p < 0.05).</p> <p>Conclusion</p> <p>There seems to be a need for defined guidelines for sealant application criteria and policy both locally and nationwide. Occlusal caries management may be improved by shifting the sealant policy from the traditional approach of prevention to interception, i.e. applying the sealants over detected or suspected enamel caries lesions instead of sealing sound teeth.</p

IL-4-secreting CD4+ T cells are crucial to the development of CD8+ T-cell responses against malaria liver stages.

CD4+ T cells are crucial to the development of CD8+ T cell responses against hepatocytes infected with malaria parasites. In the absence of CD4+ T cells, CD8+ T cells initiate a seemingly normal differentiation and proliferation during the first few days after immunization. However, this response fails to develop further and is reduced by more than 90%, compared to that observed in the presence of CD4+ T cells. We report here that interleukin-4 (IL-4) secreted by CD4+ T cells is essential to the full development of this CD8+ T cell response. This is the first demonstration that IL-4 is a mediator of CD4/CD8 cross-talk leading to the development of immunity against an infectious pathogen

Climate change research and policy in Portugal

This article offers a review of research and policy on climate change in Portugal and is organized into three main themes: scientific knowledge and assessment of climate change; policy analysis and evaluation; and public engagement. Modern scientific research on meteorology and climatology started in Portugal in the 1950s and a strong community of researchers in climate science, vulnerabilities, impacts, and adaptation has since developed, particularly in the last decade. Nevertheless, there are still many gaps in research, especially regarding the economic costs of climate change in Portugal and costs and benefits of adaptation. Governmental policies with a strong emphasis on mitigation were introduced at the end of the 1990s. As greenhouse gas emissions continued to rise beyond its Kyoto target for 2012, the country had to resort to the Kyoto Flexibility Mechanisms in order to comply. Climate change adaptation policies were introduced in 2010 but are far from being fully implemented. Regarding public engagement with climate change, high levels of concern contrast with limited understanding and rather weak behavioral dispositions to address climate change. Citizens display a heavy reliance on the media as sources of information, which are dominated by a techno-managerial discourse mainly focused on the global level. The final part of the article identifies research gaps and outlines a research agenda. Connections between policy and research are also discussed

Genetic variability in five populations of Partamona helleri (Hymenoptera, Apidae) from Minas Gerais State, Brazil

Partamona is a Neotropical genus of stingless bees that comprises 33 species distributed from Mexico to southern Brazil. These bees are well-adapted to anthropic environments and build their nests in several substrates. In this study, 66 colonies of Partamona helleri from five localities in the Brazilian state of Minas Gerais (São Miguel do Anta, Teixeiras, Porto Firme, Viçosa and Rio Vermelho) were analyzed using nine microsatellite loci in order to assess their genetic variability. Low levels of observed (Ho = 0.099-0.137) and expected (H e = 0.128-0.145) heterozygosity were encountered and revealed discrete genetic differentiation among the populations (F ST = 0.025). AMOVA further showed that most of the total genetic variation (94.24%) in P. helleri was explained by the variability within local populations

Superpulsed low-level laser therapy protects skeletal muscle of mdx mice against damage, inflammation and morphological changes delaying dystrophy progression.

Aim: To evaluate the effects of preventive treatment with low-level laser therapy (LLLT) on progression of dystrophy in mdx mice. Methods: Ten animals were randomly divided into 2 experimental groups treated with superpulsed LLLT (904 nm, 15 mW, 700 Hz, 1 J) or placebo-LLLT at one point overlying the tibialis anterior muscle (bilaterally) 5 times per week for 14 weeks (from 6th to 20th week of age). Morphological changes, creatine kinase (CK) activity and mRNA gene expression were assessed in animals at 20th week of age. Results: Animals treated with LLLT showed very few morphological changes in skeletal muscle, with less atrophy and fibrosis than animals treated with placebo-LLLT. CK was significantly lower (p = 0.0203) in animals treated with LLLT (864.70 U.l−1, SEM 226.10) than placebo (1708.00 U.l−1, SEM 184.60). mRNA gene expression of inflammatory markers was significantly decreased by treatment with LLLT (p<0.05): TNF-α (placebo-control = 0.51 µg/µl [SEM 0.12], - LLLT = 0.048 µg/µl [SEM 0.01]), IL-1β (placebo-control = 2.292 µg/µl [SEM 0.74], - LLLT = 0.12 µg/µl [SEM 0.03]), IL-6 (placebo-control = 3.946 µg/µl [SEM 0.98], - LLLT = 0.854 µg/µl [SEM 0.33]), IL-10 (placebo-control = 1.116 µg/µl [SEM 0.22], - LLLT = 0.352 µg/µl [SEM 0.15]), and COX-2 (placebo-control = 4.984 µg/µl [SEM 1.18], LLLT = 1.470 µg/µl [SEM 0.73]). Conclusion: Irradiation of superpulsed LLLT on successive days five times per week for 14 weeks decreased morphological changes, skeletal muscle damage and inflammation in mdx mice. This indicates that LLLT has potential to decrease progression of Duchenne muscular dystrophy

RNA secondary structure prediction from multi-aligned sequences

It has been well accepted that the RNA secondary structures of most functional non-coding RNAs (ncRNAs) are closely related to their functions and are conserved during evolution. Hence, prediction of conserved secondary structures from evolutionarily related sequences is one important task in RNA bioinformatics; the methods are useful not only to further functional analyses of ncRNAs but also to improve the accuracy of secondary structure predictions and to find novel functional RNAs from the genome. In this review, I focus on common secondary structure prediction from a given aligned RNA sequence, in which one secondary structure whose length is equal to that of the input alignment is predicted. I systematically review and classify existing tools and algorithms for the problem, by utilizing the information employed in the tools and by adopting a unified viewpoint based on maximum expected gain (MEG) estimators. I believe that this classification will allow a deeper understanding of each tool and provide users with useful information for selecting tools for common secondary structure predictions.Comment: A preprint of an invited review manuscript that will be published in a chapter of the book `Methods in Molecular Biology'. Note that this version of the manuscript may differ from the published versio

Complete motor recovery after acute paraparesis caused by spontaneous spinal epidural hematoma: case report

<p>Abstract</p> <p>Background</p> <p>Spontaneous spinal epidural hematoma is a relatively rare but potentially disabling disease. Prompt timely surgical management may promote recovery even in severe cases.</p> <p>Case presentation</p> <p>We report a 34-year-old man with a 2-hour history of sudden severe back pain, followed by weakness and numbness over the bilateral lower limbs, progressing to intense paraparesis and anesthesia. A spinal magnetic resonance imaging scan was performed and revealed an anterior epidural hematoma of the thoracic spine. He underwent an emergency decompression laminectomy of the thoracic spine and hematoma evacuation. Just after surgery, his lower extremity movements improved. After 1 week, there was no residual weakness and ambulation without assistance was resumed, with residual paresthesia on the plantar face of both feet. After 5 months, no residual symptoms persisted.</p> <p>Conclusions</p> <p>The diagnosis of spontaneous spinal epidural hematoma must be kept in mind in cases of sudden back pain with symptoms of spinal cord compression. Early recognition, accurate diagnosis and prompt surgical treatment may result in significant improvement even in severe cases.</p