A compendium of current developments on polysaccharide and protein-based microneedles

Microneedles (MNs), i.e. minimally invasive three-dimensional microstructures that penetrate the stratum corneum inducing relatively little or no pain, have been studied as appealing therapeutic vehicles for transdermal drug delivery. Over the last years, the fabrication of MNs using biopolymers, such as polysaccharides and proteins, has sparked the imagination of scientists due to their recognized biocompatibility, biodegradability, ease of fabrication and sustainable character. Owing to their wide range of functional groups, polysaccharides and proteins enable the design and preparation of materials with tunable properties and functionalities. Therefore, these biopolymer-based MNs take a revolutionary step offering great potential not only in drug administration, but also in sensing and response to physiological stimuli. In this review, a critical and comprehensive overview of the polysaccharides and proteins employed in the design and engineering of MNs will be given. The strategies adopted for their preparation, their advantages and disadvantages will be also detailed. In addition, the potential and challenges of using these matrices to deliver drugs, vaccines and other molecules will be discussed. Finally, this appraisal ends with a perspective on the possibilities and challenges in research and development of polysaccharide and protein MNs, envisioning the future advances and clinical translation of these platforms as the next generation of drug delivery systems.publishe

Tuberculosis among HIV-1-infected subjects in a tertiary out-patient service in São Paulo city, Brazil

Atualmente, a tuberculose (TB) é considerada a doença infecciosa mais importante entre os pacientes infectados pelo HIV-1 nos países em desenvolvimento, como o Brasil. Análise retrospectiva dos casos de tuberculose ocorridos a partir de janeiro 1995 até dezembro de 2010 foi realizada em nossa coorte de 599 pacientes HIV positivos. O desfecho primário foi a ocorrência de TB ativa, e 41 casos da doença foram diagnosticados durante este período de 16 anos. As contagens médias do nadir de células T CD4 e ao momento do diagnóstico de TB foram de 146 e 217 células/mm³, respectivamente. A carga viral média de HIV foi de 5,19 log10 cópias/mL, e 59% dos pacientes estavam em tratamento com ART. A incidência de TB foi de 1,47 casos por 100 pessoas-ano, para um tempo total de seguimento da coorte de 2775 pessoas-ano. A probabilidade de sobreviver até 10 anos após o diagnóstico foi de 75% para pacientes com TB, em oposição a 96% para pacientes com outras doenças oportunistas não-TB (p = 0,03). A tuberculose pode ser considerada problema de saúde pública entre as pessoas que vivem com HIV no Brasil, apesar da ampla utilização de anti-retrovirais para o tratamento da infecção pelo HIV / AIDS.TB is currently considered to be the most important infectious disease among HIV-1-infected subjects in developing countries, such as Brazil. A retrospective analysis of TB cases was performed, occurring from January 1995 to December 2010 in our cohort of 599 HIV positive patients. The primary outcome was the occurrence of active TB. Forty-one TB cases were diagnosed over this period of 16 years, among 599 HIV positive patients in an open cohort setting in the city of Sao Paulo, Brazil. All-time lowest mean CD4 T cell count at the time of TB diagnosis was 146 and 186 cells/mm³, respectively. The mean HIV viral load was 5.19 log10 copies/mL, and 59% of the patients were on HAART. TB incidence was 1.47 per 100 person-years, for a total follow-up time of 2775 person-years. The probability of surviving up to 10 years after diagnosis was 75% for TB patients as opposed to 96% for patients with other, non-TB opportunistic diseases (p = 0.03). TB can be considered a public health problem among people living with HIV in Brazil despite of the widespread use of antiretrovirals for the treatment of HIV infection/AIDS

Low bone mineral density among HIV-infected patients in Brazil

Decrease in bone mineral density (BMD) has been a complication among people living with HIV/AIDS. To investigate the prevalence of osteopenia/osteoporosis among HIV-infected people living in São Paulo city, we studied 108 HIV-infected patients (79 men and 29 women). We extracted data from patients’ medical records and BMD was measured by dual-energy X-ray absorptiometry (DXA). Median age of participants was 42 years (interquartile range [IQR] 36-48 years), and the median time since HIV diagnosis was 4.01 years (IQR 2-11 years). Patients had acquired HIV primarily by the sexual route (men who have sex with men 44%, heterosexual 49%). Median age, duration of HIV infection, duration of ART and CD4 nadir were similar for men and women. Plasma viral load was undetectable for 53 patients (49%). Median CD4 T cell count was 399 cells/µL (IQR 247 - 568). Twenty five patients (23%) had LBMD, and there was no statistically significant difference between men and women

Pullulan microneedle patches for the efficient transdermal administration of insulin envisioning diabetes treatment

The present study reports the fabrication of dissolvable microneedle (MN) patches using pullulan (PL), a water-soluble polysaccharide with excellent film-forming ability, for the transdermal administration of insulin, envisioning the non-invasive treatment of diabetes. PL MNs patches were successfully prepared by micromoulding and revealed good thermal stability (Tdmax = 294 °C) and mechanical properties (>0.15 N needle-1), penetrating skin up to 381 μm depth, as revealed by in vitro skin tests. After application into human abdominal skin in vitro, the MNs dissolved within 2 h releasing up to 87% of insulin. When stored at 4, 20 and 40 °C for 4 weeks, insulin was able to retain its secondary structure, as shown by circular dichroism spectropolarimetry. The prepared PL MNs were non-cytotoxic towards human keratinocytes, being suitable for skin application. These findings suggest that PL MNs have potential to deliver insulin transdermally, thus avoiding its subcutaneous administration.publishe

Rhodium catalyzed hydroformylation of kaurane derivatives: A route to new diterpenes with potential bioactivity

Kaurenic and grandiflorenic acids are naturally occurring diterpenes whose biological activity has been described. Both acids contain an exocyclic methylenic double bond that allows further functionalization on their structure. In an attempt to expand the number of derivatives of these two natural products, we have undertaken a study on the hydroformylation of the methyl esters of the two acids and the trimethylsilyl ether of kaurenol. These substrates have been hydroformylated by using unmodified Rh catalysts, as well as Rh/PPh3 and Rh/tris-(o-t-butylphenyl)phosphite catalytic systems at 100 °C and 20 bar of CO/H2 (1:1). For the three substrates, the two Rh catalysts modified with P-donor ligands, produced high conversions and chemo- and regioselectivities in the diastereoisomeric pair of linear aldehydes. In all cases, the stereoselectivity observed is strongly dependent of the system used, being the most diastereoselective the least hindered unmodified Rh/CO catalyst. A correlation between the higher diastereoselectivity and the faster [beta]-elimination of the metal-alkyl intermediate observed in the unmodified system is discussed.http://www.sciencedirect.com/science/article/B6TF5-4RVMXFD-3/1/d27e671ad9e0b7fc325dfd0bdf413c7

Modulation of the pharmacological effects of enzymatically-active PLA2 by BTL-2, an isolectin isolated from the Bryothamnion triquetrum red alga

<p>Abstract</p> <p>Background</p> <p>An interaction between lectins from marine algae and PLA₂from rattlesnake was suggested some years ago. We, herein, studied the effects elicited by a small isolectin (BTL-2), isolated from <it>Bryothamnion triquetrum</it>, on the pharmacological and biological activities of a PLA₂isolated from rattlesnake venom (<it>Crotalus durissus cascavella</it>), to better understand the enzymatic and pharmacological mechanisms of the PLA₂and its complex.</p> <p>Results</p> <p>This PLA₂consisted of 122 amino acids (approximate molecular mass of 14 kDa), its pI was estimated to be 8.3, and its amino acid sequence shared a high degree of similarity with that of other neurotoxic and enzymatically-active PLA₂s. BTL-2 had a molecular mass estimated in approximately 9 kDa and was characterized as a basic protein. In addition, BTL-2 did not exhibit any enzymatic activity.</p> <p>The PLA₂and BTL-2 formed a stable heterodimer with a molecular mass of approximately 24–26 kDa, estimated by molecular exclusion HPLC. In the presence of BTL-2, we observed a significant increase in PLA₂activity, 23% higher than that of PLA₂alone. BTL-2 demonstrated an inhibition of 98% in the growth of the Gram-positive bacterial strain, <it>Clavibacter michiganensis michiganensis </it>(Cmm), but only 9.8% inhibition of the Gram-negative bacterial strain, <it>Xanthomonas axonopodis </it>pv <it>passiflorae </it>(Xap). PLA₂decreased bacterial growth by 27.3% and 98.5% for Xap and Cmm, respectively, while incubating these two proteins with PLA₂-BTL-2 inhibited their growths by 36.2% for Xap and 98.5% for Cmm.</p> <p>PLA₂significantly induced platelet aggregation in washed platelets, whereas BTL-2 did not induce significant platelet aggregation in any assay. However, BTL-2 significantly inhibited platelet aggregation induced by PLA₂. In addition, PLA₂exhibited strong oedematogenic activity, which was decreased in the presence of BTL-2. BTL-2 alone did not induce oedema and did not decrease or abolish the oedema induced by the 48/80 compound.</p> <p>Conclusion</p> <p>The unexpected results observed for the PLA₂-BTL-2 complex strongly suggest that the pharmacological activity of this PLA₂is not solely dependent on the presence of enzymatic activity, and that other pharmacological regions may also be involved. In addition, we describe for the first time an interaction between two different molecules, which form a stable complex with significant changes in their original biological action. This opens new possibilities for understanding the function and action of crude venom, an extremely complex mixture of different molecules.</p

Coleções biológicas do Jardim Botânico do Rio de Janeiro à luz das metas da GSPC/CDB: onde estamos em 2020?

The biologic collections housed at the Jardim Botânico do Rio de Janeiro (JBRJ) go beyond herbarium exsiccatae and the arboretum, comprising also a wood-collection, carpological collection, greenhouse collection, seed and DNA baks, fungal culture and ethnobotany collections. Together the different collections add up to 665 thousand specimens, contributing substantially towards the neotropical flora knowledge. From the end of the 20th century and the beginning of the 21st, the paradigm regarding conservation and rational use of the world’s biodiversity changed, and the biological collections and their data moved from a marginal position to occupy a central role in the discussion that quantifies, qualifies, maps and studies the potential of use of biodiversity. Within this new scene, botanical gardensand their collections are totally inserted in accomplishing the tasks regarding the biodiversity targets proposed by the CBD/GSPC. In this article we map the targets that involve directly the collections of the JBRJ and analyse the contributions and limitations of our holdings in supporting the country to reach the targets of the GSPC 2020.O conjunto de coleções biológicas sob a guarda do Jardim Botânico do Rio de Janeiro (JBRJ) vai além das exsicatas do herbário e plantas vivas do arboreto, e inclui também coleções em estufas, xiloteca, carpoteca, bancos de sementes e de DNA, cultura de fungos e coleção etnobotânica. Juntas estas diferentes coleções contabilizam cerca de 665 mil espécimes, que contribuem para ampliar o conhecimento da flora neotropical. A partir do final do século XX e início do século XXI, com a mudança de paradigma envolvendo a conservação e o uso racional da biodiversidade do planeta, as coleções biológicas e seus dados associados saíram de uma posição marginal para ocupar uma posição central na discussão que quantifica, qualifica, mapeia e estuda o potencial de uso da biodiversidade. Neste novo cenário, os jardins botânicos e suas coleções estão completamente inseridos nas tarefas relacionadas a atingir as metas da biodiversidade delineadas pela CDB/GSPC. Neste artigo descrevemos quais metas envolvem diretamente as coleções do JBRJ e analisamos tanto a participação como as limitações dos nossos acervos para apoiar o país no cumprimento das metas da GSPC 2020

Beach sand and the potential for infectious disease transmission: observations and recommendations

Recent studies suggest that sand can serve as a vehicle for exposure of humans to pathogens at beach sites, resulting in increased health risks. Sampling for microorganisms in sand should therefore be considered for inclusion in regulatory programmes aimed at protecting recreational beach users from infectious disease. Here, we review the literature on pathogen levels in beach sand, and their potential for affecting human health. In an effort to provide specific recommendations for sand sampling programmes, we outline published guidelines for beach monitoring programmes, which are currently focused exclusively on measuring microbial levels in water. We also provide background on spatial distribution and temporal characteristics of microbes in sand, as these factors influence sampling programmes. First steps toward establishing a sand sampling programme include identifying appropriate beach sites and use of initial sanitary assessments to refine site selection. A tiered approach is recommended for monitoring. This approach would include the analysis of samples from many sites for faecal indicator organisms and other conventional analytes, while testing for specific pathogens and unconventional indicators is reserved for high-risk sites. Given the diversity of microbes found in sand, studies are urgently needed to identify the most significant aetiological agent of disease and to relate microbial measurements in sand to human health risk

PERFIL BIOQUÍMICO E NÍVEIS PLASMÁTICOS DE NEUTOTROFINAS DE USUÁRIOS DE CRACK EM TERAPIA DE UMA CIDADE DO EXTREMO SUL CATARINENSE, BRAZIL

O presente estudo teve como objetivou identificar o perfil bioquímico e a análise de neurotrofinas de usuários de crack e um grupo controle. Os integrantes da pesquisa foram selecionados durante 18 meses, estes, provieram dos Centros de Atenção Psicossocial para Álcool e Drogas (CAPS II ad) e a Comunidade Terapêutica (CT) da cidade de Criciúma, Santa Catarina. Após a caracterização dos indivíduos e assinatura do termo de conscentimento livre e esclarecido, foi realizada a retirada de sangue para as análises bioquímicas. Em seguida, o sangue foi centrifugado e armazenado. Parte das amostras foi enviada a um laboratório comercial para as análises de glicose, triglicerídeos, hemoglobina, colesterol total, creatinina, uréia, creatinofosfoquinase (CPK), transaminase glutâmica oxalácetica (TGO) e transaminase glutâmico-pirúvica (TGP).  Para a análise dos níveis de neurotrofina derivada do cérebro (BDNF), neurotrofina derivada da glia (NGF) e enolase neurônio específica (NSE) plasmáticas foram utilizados kits de métodos imunoenzimáticos disponíveis comercialmente. Os marcadores bioquímicos demonstraram aumento significativo nos níveis de glicose, triglicerídeos e TGP do grupo crack em relação ao grupo controle, no entanto, em ambos os casos a média dos resultados obtidos continuaram dentro dos valores de referência. Os achados apontam que os níveis BDNF do grupo crack diminuíram significativamente em comparação ao grupo controle. Por outro lado, os níveis de NGF no grupo crack apresentaram um aumento significativo em relação ao grupo controle. Destacando-se a importância da sobrevida neural, deve-se dar ênfase a este tema. Sugerem-se novos estudos para elucidar os reais mecanismos envolvidos nestes fatores

Valores como predictores de satisfacción con la vida en los jóvenes

Numa perspectiva funcionalista, os valores são uma expressão cognitiva das necessidades humanas, princípios que orientam o comportamento para metas mais pessoais, sociais ou gerais de vida, cujo impacto psicossocial merece mais investigação. Neste estudo, analisou-se em que medida o tipo de orientação dos valores prediz a satisfação com a vida de 562 jovens portugueses (n = 303, 53,9% mulheres), com idades entre 14 e 22 anos (M = 16,9, DP = 1,71), que frequentam o ensino médio: via profissionalizante (63,7%) e regular (36,3%). Os jovens completaram o Questionário de Valores Básicos e a Escala de Satisfação com a Vida. Os resultados da análise de regressão linear indicam que a orientação dos valores explica menos de um quarto da variabilidade da satisfação com a vida, o que suscita a necessidade de se analisar o seu poder explicativo em conjunto com outras variáveis, por exemplo, de personalidade e sociocognitivas.In a functionalist perspective, values are a cognitive expression of human needs as well as principles that guide behaviors to personal, social or general life goals, whose psychosocial impact deserves more investigation. This study aimed to analyze whether the type of values orientation predicts life satisfaction in 562 Portuguese youths (n = 303, 53.9% women) aged 14 to 22 years (M = 16.9; SD = 1.71), attending high school studies, being 63.7% technical and (36.3%) regular high school.Students completed the Basic Values Survey and the Satisfaction With Life Scale. The results of the linear regression analyzes indicate that the values orientation explains less than a quarter of life satisfaction variability, which indicated the need to further analyze its explanatory power together with other variables, such as, personality and socio-cognitive.Desde el punto de vista funcional, los valores son una expresión cognitiva de las necesidades humanas, principios que orientan el comportamiento hacia metas más personales, sociales o generales de vida, cuyo impacto psicosocial necesita más investigación. En este estudio se analizó en qué medida el tipo de orientación de los valores predice la satisfacción con la vida de 562 jóvenes portugueses (n = 303, 53.9% mujeres), con edades entre 14 y 22 años ( = 16.9, P = 1.71) que frecuentan Enseñanza Secundaria: profesional (63.7%) y normal (36.3%). Los jóvenes completaron el Cuestionario de Valores Básicos y la Escala de Satisfacción con la Vida. Los resultados del análisis de regresión lineal indican que la orientación de los valores explica menos de una cuarta parte de la variabilidad de satisfacción con la vida, lo que plantea la necesidad de analizar su poder explicativo, junto con otras variables, por ejemplo, de personalidad y socio-cognitivas.(undefined)info:eu-repo/semantics/publishedVersio