Abstract Dermatitis is defined as a set of inflammatory diseases that affect the skin, with varied causes. Among the different types of dermatitis, contact dermatitis is the most prevalent. Although the current therapy is often effective, it is associated with adverse effects and the possibility of drug tolerance. N-Methyl-(2S, 4R)-trans-4-hydroxy-L-proline is a L-proline amino acid derivative found in the leaves of Sideroxylon obtusifolium, a species traditionally used to treat inflammatory diseases. The aim of this study was to investigate the topical anti-inflammatory effect of N-methyl-(2S, 4R)-trans-4-hydroxy-L-proline (NMP) in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced irritant contact dermatitis in mice. Topically administered NMP, at doses of 0.03 − 0.50 mg/ear, reduced TPA-induced ear edema and neutrophil migration, as evidenced by low tissue myeloperoxidase activity and verified by histological examination. In addition, NMP (0.06 mg/ear) reduced tissue levels of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, INF-γ and MCP-1) and of the anti-inflammatory cytokine IL-10, and reduced gene expression of TNF-α, IL-6 and IL-1β increased by TPA. The data suggest that N-methyl-(2S, 4R)-trans-4-hydroxy-L-proline acts as a topical anti-inflammatory agent that decreases the expression of inflammatory cytokines, making it useful for the treatment of skin inflammation. Further investigations are necessary for its development as a therapeutic agent.

Various beneficial biological activities have been reported for passion fruit (Passiflora edulis), grown in tropical and subtropical regions. However, no study has yet demonstrated its action against the Zika virus (ZIKV) infection. The present study aimed to investigate the anti-ZIKV of the ethanolic passion fruit seed extract (PFSE), from which, liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis allowed to putatively annotate the occurrence of piceatannol, astringin, scirpusin A, scirpusin B, isookanin-7-O-glucoside and naringenin-7-O-glucoside, two quadranguloside derivatives, tyrosine, and phenylalanine. PFSE is well tolerated by cell lines (Vero E6 and HTR-8/SVneo) and tissue explants from the human placenta. With 1- and 24-h treatments, PFSE consistently reduced the viral load and NS1 protein expression of the two strains of ZIKV (MR766 and PE243) in placental explants and cell lines. Thus, PFSE has a promising potential for developing anti-ZIKV treatments, protecting the placenta against infection caused by ZIKV, along with relevant antioxidant potential, represented by ferric reducing antioxidant power (FRAP) of 390.5 Trolox eq per g dry extract and half maximal inhibitory concentration (IC50) for 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•) of 12.1 µg mL-1, and more than 90% protection from lipid peroxidation. Although further studies need to be conducted, PFSE treatment was safe and effective in trophoblast cells and placental explants, thus representing a promising class of all-accessible products based on the reuse of industrial by-products.

The phytochemical reinvestigation from the heartwood of the extracts of Cordia glazioviana led to the isolation of four still undescribed hydroquinones derivatives designated as cordiaquinol D (1), cordiaquinol E (2), (10R)-10,11-dihydrofuran-1,4-dihydroxy-globiferin (3) and 2-[(1’E,6’E)-3’,8’- dihydroxy-3’,7’-dimethylocta-1’,6’-dienyl]-benzene-1,4-diol (4), along with the naphthoquinone 6-[(2’R)-2’-hydroxy-3’,6’-dihydro-2H-pyran-5’-yl]-2-methoxy-7-methylnaphthalene-1,4-dione (5). Additionally, six previously known compounds were also isolated: rel-1,4-dihydroxy-8(,11(;9(,11(-diepoxy-2-methoxy-8a(-methyl-5,6,7,8,8a,9,10,10a-octahydro-10-antracenone (6), didehydroconicol (7), 1(,6(-dihydroxy-7-epi-eudesm-3-ene (8), 1(,6(-dihydroxy-7-epi-eudesm-4(15)-ene (9), 10,11-dihydroxybisabolol (10), and hamanasal-A (11). The structures of the new compounds were assigned by high-resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR) analyses. The relative stereochemistry of 3, 4, and 5 was improved by quantum mechanical calculations. Eight, out of the eleven isolated compounds (2-9), were tested through cellular viability and lipopolysaccharide (LPS)-induced inflammation assays against RAW 264.7 macrophage-like cells. Compounds 3-5 exhibited a stronger effect on LPS-induced NO production (half-maximal inhibitory concentration (IC50) 50.34, 105.83, and 66.73 µM, respectively).

Folhas de Byrsonima sericea são amplamente utilizadas na medicina popular no Brasil no tratamento de distúrbios gástricos. Este estudo investigou os constituintes químicos do extrato etanólico das folhas de B. sericea (BSLE) e sua atividade gastroprotetora com seus possíveis mecanismos de ação utilizando o modelo de lesão gástrica induzida por etanol em camundongos. A análise fitoquímica foi realizada para identificar os componentes ativos presentes no extrato e análise por HPLC foi realizada para a identificação de flavonóides. A administração de BSLE (v.o.) nas doses de 125, 250, 500 mg/kg, v.o. atenuou significativamente as lesões gástricas induzidas por etanol em 53,2, 84,9 e 87,6% respectivamente. BSLE (250 mg/kg) preveniu a depleção do muco gástrico, de grupamentos sulfidrílicos não-protéicos (GSH), das atividades da SOD e da CAT assim como o aumento de malonaldeído promovido pelo etanol. Além disso, o efeito gastroprotetor do BSLE foi significantemente reduzido pelos pré-tratamentos com capsazepina (i.p.), L-NAME (i.p.) ou glibenclamida (i.p.), respectivamente bloqueadores/inibidores de receptores TRPV1, NO sintase e canais de K+ATP. A investigação fitoquímica revelou a presença de flavonoides como rutina, isoquercitrina, 3-O-rutinosideo-canferol e quercetina que são conhecidas por suas propriedades antioxidantes e gastropotetoras. O estudo demonstrou que BSLE proporciona ação gastroprotetora através de vários mecanismos que podem ser úteis no tratamento de patologias associadas a disfunções gástricas.

Byrsonima sericea leaves are extensively used in folk medicine in Brazil against gastric disorders. This study investigated the chemical constituents of B. sericea leaf ethanolic extract (BSLE) and its potential gastroprotective activity, with its possible mechanism of the action using ethanol to induce gastric mucosal damage in mice. The phytochemical analysis was carried out to identify the active constituents present in the extract, and the HPLC analysis was performed for the identification of flavonoids. BSLE at oral doses of 125, 250 and 500 mg/kg markedly attenuated the ethanol-evoked gastric lesions by 53.2, 84.9 and 87.6 %, respectively. The BSLE (250 mg/kg) prevented the depletion of gastric mucus and gastric mucosal nonproteic-sulfhydryl groups, SOD and CAT, as well as the increase in the MDA content promoted by absolute ethanol. Moreover, the effect of BSLE against ethanol damage was found to be significantly reduced in mice pretreated with Capsazepine (i.p.), L-NAME (i.p.) or glibenclamide (i.p.), the respective blockers/inhibitors of TRPV1, NO synthase and K+ATP channel. The phytochemical investigation on BSLE revealed the presence of flavonoids rutin, isoquercitrin, kaempferol 3-O-rutinoside and quercetin, which are compounds well known for their antioxidant and gastroprotective properties. These results suggest that BSLE affords gastroprotection through multiple mechanisms, which may be helpful in the treatment of pathologies associated with gastric dysfunctions.

OBJETIVO: Descrever procedimento cirúrgico de anuloplastia concêntrica do anel mitral sem prótese, isolada ou associada à ressecção quadrangular com plicatura póstero-medial do anel mitral, e analisar os resultados imediatos e tardios obtidos. MÉTODO: Entre fevereiro de 1986 e fevereiro de 2001, realizamos 790 procedimentos abordando a valva mitral, 41 foram realizados em crianças e adolescentes menores de 20 anos (média de 9,7 anos). Vinte (48,7%) pacientes eram do sexo feminino e 21 (51,3%) do masculino. A doença reumática foi responsável pelas lesões em 92,6% dos casos e a degeneração mixomatosa em apenas 7,4%. No período pré-operatório, 22 (53,6%) pacientes estavam em classe funcional III e 19 (46,4%) em classe funcional IV, advindos de repetidos surtos de febre reumática, agravados pela desnutrição. A técnica cirúrgica utilizada foi a anuloplastia concêntrica, aplicada isoladamente ou em associação à ressecção quadrangular com plicatura póstero-medial. O curso do seguimento pós-operatório foi de 7 meses a 15 anos (3/2/1986 a 12/2/2001). RESULTADOS: A mortalidade hospitalar foi de 2,4%. Os pacientes receberam alta sem sopro sistólico de regurgitação mitral. Dois pacientes apresentaram, ao longo dos anos (4 e 11 anos), estenose mitral e necessitaram reoperação, um deles operado com dois anos de idade. Dois doentes foram reoperados para corrigir disfunção aórtica previamente abordada por plastia (12 e 18 meses após a primeira operação), morrendo e contribuindo para mortalidade tardia de 5%. CONCLUSÃO: Consideramos a técnica empregada um procedimento alternativo, válido, de aplicação preferencial em crianças e adolescentes, de fácil reprodução e de baixíssimo custo.

OBJECTIVE: To describe the mitral anuloplasty technique either in isolation or associated with posterior quadrantectomy and to analyze the immediate and late results in young patients. METHOD: Between February 1986 and February 2001, 790 mitral valve procedures were performed in our Institution including 41 annuloplaties in patients with ages ranging from 1 to 20 years (Mean age = 9.7 years). 51.7% were males. The main etiologies were rheumatic disease (92.6%) and myxomatous degeneration (7.4%). Twenty-two (53.6%) patients were preoperatively in functional class III (NYHA), and 19 (46.4%) in class IV (NYHA), some in course of rheumatic fever aggravated by malnutrition. The technique employed was concentric mitral annuloplasty either in isolation or associated with posterior quadrantectomy. The follow-up ranged from 7 months to 15 years. RESULTS: The hospital mortality rate was 2.4%. All patients were discharged without mitral regurgitation. Two patients coursed with mitral stenosis (after 4 and 11 years respectively) and valve replacement was needed. Two patients coursed with aortic insufficiency (after 12 and 18 months) and died after aortic valve replacement, contributing to a 5% late mortality rate. CONCLUSION: In conclusion, mitral annuloplasty without ring either in isolation or associated with posterior quadrantectomy is a safe, easily reproducible especially in young patients.