Polymorphisms and haplotypes of TOLLIP and MUC5B are associated with susceptibility and survival in patients with fibrotic hypersensitivity pneumonitis.

INTRODUCTION AND OBJECTIVES: Hypersensitivity pneumonitis (HP) is an interstitial lung disease with diverse clinical features that can present a fibrotic phenotype similar to idiopathic pulmonary fibrosis (IPF) in genetically predisposed individuals. While several single nucleotide polymorphisms (SNPs) have been associated with IPF, the genetic factors contributing to fibrotic HP (fHP) remain poorly understood. This study investigated the association of MUC5B and TOLLIP variants with susceptibility, clinical presentation and survival in Portuguese patients with fHP. MATERIAL AND METHODS: A case-control study was undertaken with 97 fHP patients and 112 controls. Six SNPs residing in the MUC5B and TOLLIP genes and their haplotypes were analyzed. Associations with risk, survival, and clinical, radiographic, and pathological features of fHP were probed through comparisons among patients and controls. RESULTS: MUC5B rs35705950 and three neighboring TOLLIP variants (rs3750920, rs111521887, and rs5743894) were associated with increased susceptibility to fHP. Minor allele frequencies were greater among fHP patients than in controls (40.7% vs 12.1%, P<0.0001; 52.6% vs 40.2%, P = 0.011; 22.7% vs 13.4%, P = 0.013; and 23.2% vs 12.9%, P = 0.006, respectively). Haplotypes formed by these variants were also linked to fHP susceptibility. Moreover, carriers of a specific haplotype (G-T-G-C) had a significant decrease in survival (adjusted hazard ratio 6.92, 95% CI 1.73-27.64, P = 0.006). Additional associations were found between TOLLIP rs111521887 and rs5743894 variants and decreased lung function at baseline, and the MUC5B SNP and radiographic features, further highlighting the influence of genetic factors in fHP. CONCLUSION: These findings suggest that TOLLIP and MUC5B variants and haplotypes may serve as valuable tools for risk assessment and prognosis in fibrotic hypersensitivity pneumonitis, potentially contributing to its patient stratification, and offer insights into the genetic factors influencing the clinical course of the condition.

Heterogeneity of elemental composition and natural abundance of stables isotopes of C and N in soils and leaves of mangroves at their southernmost West Atlantic range.

Mangrove communities were selected in the state of Santa Catarina, Brazil, near their southernmost limit of distribution, to study mineral nutrient relation in soils and plants. Communities included three true mangrove species, Rhizophora mangle, Laguncularia racemosa and Avicennia germinans, and two associated species, the fern Acrostichum danaeifolium, and the grass Spartina densiflora. The sites included communities in the lower Río Tavares near Florianopolis city, Sonho beach near Palhoça city, and the Santo Antonio lagoon. These sites included a full range of mangroves under humid climate where winter temperatures, instead of salinity, may be the main factor regulating their productive capacity and species composition. Soil salinity was determined by the concentration of soluble Na, and soil C and N were linearly correlated indicating their association in organic matter. Tavares site showed higher specific conductivity, and concentrations of Na and Mg in the soil layer below 40 cm depth, indicating larger influence of marine water. Isotopic signature of C increased with soil depth suggesting that microorganisms decomposing organic matter are releasing 13C depleted CO2. Nitrogen isotopic signature decreased with soil depth, indicating enrichment in 15N possibly as a result of denitrification in the upper soil layers. Mineral elements in leaf tissues showed A. schaueriana with higher concentrations of N, P, Na, K, Cu, Zn, and Na/Ca ratio. Spartina densiflora was characterized by the lowest N and K concentrations, and the highest concentrations of Al and Fe. Rhizophora mangle and L. racemosa had the highest Ca concentrations. Carbon isotopic signatures identified S. densiflora as a C4 plant, and A. schaueriana as the mangrove species occupying comparatively more water stressed microsites than the rest. Leaf nitrogen isotopic signatures were positive, in correspondence with the soil values. The results support the hypothesis that sites sampled were comparatively fertile, because sediment transport through fresh water run-off is predominant in humid coasts, and therefore plants were not limited by nutrient supply, nor particularly stressed by soil salinity.

Anatomic-radiographic aspects and gastrointestinal transit time in Boa constrictor amarali Stull, 1932 (Squamata, Boidae) / [Aspectos anátomo-radiográficos e tempo de trânsito gastrointestinal em jiboia-cinzenta Boa constrictor amarali Stull, 1932 (Squamata, Boidae)]

The goal of this study was to describe the gastrointestinal transit technique in the Boa constrictor amarali. For that purpose, we obtained simple radiographic images of seven serpents, subsequently administering a 25mL/kg dose of barium sulfate and establishing a radiographic sequence at the following times: 5 minutes; 1, 2, 3, 6, 9, 24, 48, 72 and 96 hours, extending to 120 and 126 hours for one animal. The mean esophageal transit was 26.71±19.48 hours; the mean gastric filling time was 28.57±27.22 minutes and the emptying time was 60±12 hours; the mean filling time of the contrast medium in the small intestine was 3±2.16 hours and the emptying time was 97±15.65 hours. We also obtained the mean filling time of the large intestine, which was 40±11.31 hours. We found that the mean passage time of the contrast medium through the cranial gastrointestinal tract - until the complete elimination of barium sulfate from the small intestine -was 97±15.65 hours. In addition to determining the gastrointestinal transit time, the technique used allowed for the morphological identification of the alimentary canal.(AU)

O objetivo deste trabalho foi descrever a técnica de trânsito gastrointestinal em Boa constrictor amarali. Para tanto, foram obtidas radiografias simples de sete serpentes, e, subsequentemente a essas, foi administrado sulfato de bário na dose de 25mL/kg. A partir disso, foi estabelecida a sequência radiográfica nos seguintes tempos: cinco minutos; uma, duas, três, seis, nove, 24, 48, 72 e 96 horas, e em um animal estendeu-se para 120 e 126 horas. O trânsito esofágico médio foi de 26,71±19,48 horas, o tempo médio de preenchimento gástrico foi de 28,57±27,22 minutos, e o esvaziamento de 60±12 horas; a média de tempo de enchimento do meio de contraste no intestino delgado foi de 3±2,16 horas e, por fim, o esvaziamento foi de 97±15,65 horas, e ainda obteve-se o tempo médio de enchimento do intestino grosso igual a 40±11,31 horas. Desse modo, verificou-se que a média do tempo de passagem do contraste pelo trato gastrointestinal cranial - até a completa eliminação do sulfato de bário do intestino delgado - foi de 97±15,65 horas. Além da determinação do tempo de trânsito gastrointestinal, a técnica empregada permitiu a identificação morfológica do canal alimentar.(AU)

Heterogeneity of elemental composition and natural abundance of stables isotopes of C and N in soils and leaves of mangroves at their southernmost West Atlantic range / Heterogeneidade da composição elementar e abundância natural de isótopos estáveis de C e N no solo e folhas dos manguezais no extremo sul da sua distribuição na costa Atlântica ocidental

Abstract Mangrove communities were selected in the state of Santa Catarina, Brazil, near their southernmost limit of distribution, to study mineral nutrient relation in soils and plants. Communities included three true mangrove species, Rhizophora mangle, Laguncularia racemosa and Avicennia germinans, and two associated species, the fern Acrostichum danaeifolium, and the grass Spartina densiflora. The sites included communities in the lower Río Tavares near Florianopolis city, Sonho beach near Palhoça city, and the Santo Antonio lagoon. These sites included a full range of mangroves under humid climate where winter temperatures, instead of salinity, may be the main factor regulating their productive capacity and species composition. Soil salinity was determined by the concentration of soluble Na, and soil C and N were linearly correlated indicating their association in organic matter. Tavares site showed higher specific conductivity, and concentrations of Na and Mg in the soil layer below 40 cm depth, indicating larger influence of marine water. Isotopic signature of C increased with soil depth suggesting that microorganisms decomposing organic matter are releasing 13C depleted CO2. Nitrogen isotopic signature decreased with soil depth, indicating enrichment in 15N possibly as a result of denitrification in the upper soil layers. Mineral elements in leaf tissues showed A. schaueriana with higher concentrations of N, P, Na, K, Cu, Zn, and Na/Ca ratio. Spartina densiflora was characterized by the lowest N and K concentrations, and the highest concentrations of Al and Fe. Rhizophora mangle and L. racemosa had the highest Ca concentrations. Carbon isotopic signatures identified S. densiflora as a C4 plant, and A. schaueriana as the mangrove species occupying comparatively more water stressed microsites than the rest. Leaf nitrogen isotopic signatures were positive, in correspondence with the soil values. The results support the hypothesis that sites sampled were comparatively fertile, because sediment transport through fresh water run-off is predominant in humid coasts, and therefore plants were not limited by nutrient supply, nor particularly stressed by soil salinity.

Resumo Foram selecionadas florestas de mangue próximas ao limite sul de distribuição dos manguezais, no estado de Santa Catarina, Brasil, para o estudo do conteúdo de nutrientes no solo e em tecido vegetal. As comunidades estudadas eram compostas por três espécies típicas de mangue: Rhizophora mangle, Laguncularia racemosa e Avicennia germinans, e duas espécies associadas: a samambaia-do-brejo, Acrostichum danaeifolium, e a herbácea Spartina densiflora. Os locais de estudo incluiram comunidades no curso inferior do Rio Tavares na cidade de Florianópolis; Praia do Sonho, próxima à cidade de Palhoça e a Lagoa de Santo Antonio. Esses locais incluiram manguezais submetidos a clima úmido, onde as temperaturas do inverno, mais do que a salinidade, são o principal fator regulador da capacidade produtiva do sistema e da composição de espécies. A salinidade do solo foi determinada pela concentração de Na solúvel. Os conteúdos de Carbono e Nitrogênio no solo apresentaram correlação linear, indicando sua associação na matéria orgânica. A área do Rio Tavares apresentou maior influência marinha evidenciada pelas altas condutividade específica e concentrações de Na e Mg nas camadas do solo abaixo de 40 cm de profundidade. A assinatura isotópica do C aumentou com a profundidade no solo, o que sugere que microorganismos decompositores da matéria orgânica estão liberando CO2 pobre em 13C. A assinatura isotópica do Nitrogênio diminui com a profundidade do solo, indicando enriquecimento em 15N, possivelmente como resultado de processo de denitrificação nos níveis superiores do solo. Os tecidos foliares de A. schaueriana apresentaram as maiores concentrações de N, P, Na, K, Cu, Zn, e da razão Na/Ca. Spartina densiflora apresentou as menores concentrações de N e K e as maiores concentrações de Al e Fe. Rhizophora mangle e L. racemosa apresentaram as maiores concentrações de Ca. Os resultados da assinatura isotópica de Carbono identificam S. densiflora como uma planta C4 e A. schaueriana como a espécie de mangue que ocupa os locais com maior estresse hidrico. As assinaturas isotópicas do Nitrogênio foram positivas, estando de acordo com os valores observados para o solo. Os resultados sustentam a hipótese de que os locais estudados são fertéis, pois o escoamento superficial de água doce é predominante em costas úmidas e, portanto, as plantas não estão sujeitas à limitação por aporte de nutrientes e não estão submetidas a estresse salino.

Phototactic behavior in Daphnia magna Straus as an indicator of toxicants in the aquatic environment.

In this study, the phototactic behavior of Daphnia magna was investigated as a possible bioindicator for the following 11 chemicals commonly found in the aquatic environment: benzo(b)fluoranthene, mercury (II) chloride, dimethoate, lindane, linuron, MCPA, TBTO, carbon tetrachloride, thiram, 2,4,6-trichlorophenol and arsenic trioxide. Phototactic response was monitored as the movement of 7 to 8 day-old D. magna individuals. The analysis was carried out using glass test tubes divided radially into two zones, with increasing distance from a light source. For each of the compounds, different concentrations and exposure times were analyzed, and the behavior of the D. magna in each of the treatments compared to the controls in which the chemicals were not added. Using the experimental model described here, all of the 11 chemicals could be detected following exposure times of between 15 min and 48 h. The lowest concentrations detected using this technique were between 2 and 43 times lower than the LC(50) and EC(50) values reported for D. magna. The results of this study show that the analysis of phototactism is a useful method for detecting the presence of a wide range of potentially toxic chemicals found in the aquatic environment.

Avaliação da atividade antimicrobiana do extrato etanólico bruto da casca da sucupira branca (Pterodon emarginatus Vogel) - Fabaceae / Evaluation of antimicrobial activity of crude ethanol extract from the bark of "sucupira branca" (Pterodon emarginatus Vogel) - Fabaceae

Pterodon emarginatus Vogel (Fabaceae) é uma árvore do Cerrado conhecida popularmente como "sucupira branca, faveiro, fava de sucupira e sucupira lisa" e utilizada na medicina popular em preparações anti-reumáticas, antiinflamatórias, analgésicas e antiinfecciosas. Esse trabalho teve por objetivo fazer a triagem fitoquímica do pó e avaliar a atividade antimicrobiana do extrato etanólico bruto das cascas da P. emarginatus contra bactérias Gram-positivas, Gram-negativas e o fungo Candida albicans. O extrato etanólico bruto foi obtido a partir das cascas dessecadas e pulverizadas. A concentração inibitória mínima (CIM) do extrato bruto foi determinada utilizando-se o inoculador de Steers. Os testes fitoquímicos detectaram a presença de flavonóides, heterosídeos saponínicos, resinas e traços de esteróides e triterpenóides. As CIM do extrato etanólico foram de 0,18 mg mL-1 para as bactérias Gram-positivas Rhodococcus equi ATCC 25923, Micrococcus luteus ATCC 9341, Micrococcus roseus IPTSP/UFG e para as bactérias Gram-negativas Serratia marcescens ATCC 14756 e Pseudomonas aeruginosa ATCC 9027; de 0,37 mg mL-1 para a Enterobacter cloacae FT 505 LEMC/EPM/UFG e de 0,74 mg mL-1 para as demais bactérias testadas e para o fungo C. albicans. O presente estudo abre perspectivas para o uso da cascas da P. emarginatus como antimicrobiano.

Pterodon emarginatus Vogel (Fabaceae) is a Cerrado tree popularly known as "sucupira branca", "faveiro", "fava de sucupira" and "sucupira lisa" and has been used in folk medicine as antirheumatic, anti-inflammatory, analgesic and anti-infective. The aim of this work was to perform the phytochemical screening of the powder and to evaluate the antimicrobial activity of crude ethanol extract from P. emarginatus barks against Gram-positive bacteria, Gram-negative bacteria and the fungus Candida albicans. The crude ethanol extract was obtained from desiccated and pulverized barks. Its minimum inhibitory concentration (MIC) was determined by using Steers inoculator. The phytochemical tests detected the presence of flavonoids, saponin heterosides, resins and traces of steroids and triterpenoids. Ethanol extract MICs were 0.18 mg mL-1 for the Gram-positive bacteria Rhodococcus equi ATCC 25923, Micrococcus luteus ATCC 9341 and Micrococcus roseus IPTSP/UFG, and for the Gram-negative bacteria Serratia marcescens ATCC 14756 and Pseudomonas aeruginosa ATCC 9027; 0.37 mg mL-1 for Enterobacter cloacae FT 505 LEMC/EPM/UFG; and 0.74 mg mL-1 for the remaining tested bacteria and for the fungus C. albicans. This study opens perspectives for the use of P. emarginatus barks as an antimicrobial drug.

Análise da atividade antimicrobiana das folhas de Davilla elliptica St.-Hil. (Dilleniaceae) / Investigation of antimicrobial activity of Davilla elliptica St.-Hil. leaves (Dilleniaceae)

Davilla elliptica St.-Hil. (Dilleniaceae) é um arbusto,usado popularmente como adstringente, tônico, sedativo, diurético, no tratamento de hemorróidas, hérnia e em aplicações tópicas como anti-séptico na limpeza de ferimentos. O presente estudo teve por objetivo avaliara atividade antimicrobiana dos extratos etanólicos brutos das folhas de D. elliptica coletadas em Alexânia e Goiânia, Goiás, Brasil. Os extratos etanólicos brutos foram obtidos, por maceração a frio, a partir das folhas dessecadas e pulverizadas. A atividade antimicrobiana foi avaliada utilizando 25 cepas de microrganismos (Gram-negativos, Gram-positivos e levedura) através da determinação da Concentração Inibitória Mínima (CIM) utilizando-se o inoculador de Steers. Os extratos obtidos de plantas coletados nas duas localidades inibiram o crescimento de todas as cepas avaliadas. O extrato da amostra coletada em Alexânia apresentou atividade antimicrobiana com CIM variando de 0,371 mg/mL a 0,743 mg/mL. O extrato da amostra coletada em Goiânia apresentou CIM variando de < 0,023 mg/mL a 11,9 mg/mL. Os extratos etanólicos brutos das folhas de D. elliptica foram mais ativos contra as bactérias Gram-positivas do que para as bactérias Gram-negativas.

Davilla elliptica St.-Hil.(Dilleniaceae) is a shrub, whose leaves are traditionally used in Brazilian popular medicine as an astringent, tonic, sedative and diuretic and to treat hemorrhoids and hernia and it is applied a topical antiseptic to clean wounds. The aim in this study was to assess the antimicrobial activity of crude ethanol extracts of D. elliptica leaves collected in the towns of Alexânia and Goiânia, state of Goiás, Brazil. The crude extracts were obtained by cold maceration, of the dried and pulverized leaves in ethanol. Antimicrobial activities against 25 strains of microorganisms (Gram-negative bacteria, Gram-positive bacteria and a yeast) were tested determining by the Minimal Inhibitory Concentration (MIC) in agar plates inoculated with using a Steers replicator. Extracts of from inhibited the growth of all strains evaluated. The extract of the sample collected in Alexânia showed antimicrobial activity with MICs ranging from 0.371 mg/mL to 0.743 mg/mL, while that collected in Goiânia showed MICs ranging from <0.023 mg/mL to 11.9 mg/mL. The D. elliptica crude leaf ethanol extracts evaluated were more active against Gram-positive than Gram-negative bacteria.

Avaliação da atividade antimicrobiana das partes aéreas (folhas e caules) e raízes de Richardia brasiliensis Gomez (Rubiaceae) / Assessment of antimicrobial activity of aerial parts (leaves and stems) and roots of Richardia brasiliensis Gomez (Rubiaceae)

Richardia brasiliensis é uma planta utilizada popularmente como expectorante, emética, diaforética, vermífuga e para o tratamento de hemorróidas. O presente estudo objetivou realizar a prospecção fitoquímica e avaliar a ação antimicrobiana do extrato bruto das partes aéreas e raízes de R. brasiliensis. O extrato etanólico bruto foi obtido a partir do material botânico dessecado e pulverizado. O pó das partes aéreas e raízes foram submetidos à triagem fitoquímica. A atividade antimicrobiana foi realizada contra bactérias Gram-positivas esporuladas e não esporuladas, Gram negativas e a levedura Candida albicans através da determinação da concentração inibitória mínima por diluição em ágar empregando-se o inoculador de Steers. A triagem fitoquímica evidenciou a presença de esteróides, triterpenóides, cumarinas, resinas, alcaloides e flavonóides. A CIM do extrato das partes aéreas variou de 0,37 a 0,74 mg/mL e das raízes de 0,74 a 11,9 mg/mL. Concluiu-se que tanto o extrato etanólico bruto das partes aéreas quanto das raízes apresentaram atividade antimicrobiana.

Richardia brasiliensis is a neotropical perennial her bused in Brazilian popular medicine as an expectorant, emetic, diaphoretic, vermifuge and to treat hemorrhoids. This paper reports the phytochemical screening and the antimicrobial activity of crude ethanol extracts of the aerial parts and roots of this plant. The crude ethanol extracts were prepared from dried, pulverized botanical material. The aerial parts and roots powder was screened for classes of phytochemicals. The antimicrobial activity was tested against spore-forming and non-sporing Gram-positive bacteria, Gramnegative bacteria and Candida albicans by the agardilution method, inoculating the series of plates at multiple points with a Steers replicator to determine the minimum inhibitory concentration (MIC) of each organism. The phytochemical screening showed the presence of steroids, triterpenes, coumarins, resins, alkaloids and flavonoids. The MIC of the extract of aerial parts varied from 0.37 to 0.74 mg/mL and that of the roots from 0.74 to 11.9 mg/mL. It was concluded that the crude ethanolic extracts of both the aerial parts and the roots showed antimicrobial activity.

Caracterização farmacognóstica de folhas de Davilla elliptica St.-Hil. (Dilleniaceae) / Pharmacognostic characterization of the leaves of Davilla elliptica St.-Hil. (Dilleniaceae)

Davilla elliptica St.-Hil. é empregada popularmente no tratamento de hemorróidas, diarréias e ferimentos. O propósito deste trabalho foi realizar o estudo farmacognóstico de folhas de D. elliptica de dois locais do Estado de Goiás. Cortes paradérmicos e transversais foram submetidos a técnicas usuais de microscopia óptica. As folhas de D. elliptica são hipoestomáticas, sendo os estômatos predominantemente paracíticos. Na epiderme observam-se tricomas unicelulares em ambas faces. O mesofilo é isobilateral e apresenta idioblastos cristalíferos. O sistema vascular na nervura principal é constituído por três feixes vasculares, formando uma estrutura circular. No pecíolo o sistema vascular apresenta uma estrutura circular formada, provavelmente, pela união de vários feixes vasculares. O material pulverizado foi submetido a testes de prospecção fitoquímica, de pureza e quantitativo. Foi constatada a presença de taninos, cumarinas, resinas, flavonóides, saponinas, esteróides e triterpenóides. Os teores de cinzas totais foram de 10,32 por cento e 12,26 por cento; os de cinzas insolúveis em ácido, 7,46 por cento e 9,68 por cento; e os de umidade, 9,92 por cento e 9,50 por cento. Os teores de flavonóides totais foram de 1,20 por cento e 1,48 por cento, e os de taninos 9,89 por cento e 13,96 por cento. Devido ao número reduzido de amostras, não é possível afirmar, através deste estudo, que o perfil farmacognóstico de D. elliptica seja influenciado por fatores abióticos.

Davilla elliptica St.-Hil. is popularly used in the treatment of hemorrhoid, diarrhea and wounds. The aim of this work was to characterize pharmacognosticaly two leaves samples of D. elliptica. Paradermal and transversal sections had been submitted the usual techniques of optical microscopy. The leaves of D. elliptica are hypostomatics, and the stomata predominantly paracytic. In both epidermis were observed unicellular non-glandular trichomes. The mesophyll is isolateral and shows idioblasts with crystals in raphide. The vascular system in the midrib is constituted by three vascular bundles, forming a circular structure. The petiole shows a circular structure probably formed by union of many vascular bundles localized in the central region. The powdered plant material was submitted to tests of phytochemical prospection, of purity and quantitative. There had been evidenced the presence of tannins, coumarins, resins, flavonoids, saponins and steroids. The content of total ashes was of 10,32 percent and 12,26 percent, insoluble in acid of 7,46 percent and 9,68 percent; the humidity of 9,92 percent and 9,50 percent. The flavonoids contents was of 1,20 percent and 1,48 percent; the tannins contents was of 9,89 percent and 13,96 percent. Because of the reduced number of samples, it was not possible to affirm through this study that the pharmacognostic profile de D. elliptica is influenced by abiotics factors.