Jungia sellowii suppresses the carrageenan-induced inflammatory response in the mouse model of pleurisy

This study was conducted to explore the anti-inflammatory effect of Jungia sellowii (Asteraceae) using a murine model of pleurisy induced by carrageenan (Cg). This plant is used in southern Brazil to treat inflammatory diseases. J. sellowii leaves were extracted with ethanol/water to obtain the crude extract (CE), which was fractionated with different solvents, yielding n-hexane (Hex), dichloromethane (DCM), ethyl acetate (EtOAc) and n-butanol (BuOH) fractions, and aqueous fraction (Aq). The major compounds succinic acid (SA) and lactic acid (LA) were isolated from Aq fraction, and their structures were determined by ¹H and ¹³C NMR. Pleurisy was induced by Cg (Saleh et al. 1996). The leukocytes, exudation, myeloperoxidase (MPO) and adenosine–deaminase (ADA) activities, metabolites of nitric oxide (NO _x ) levels, protein levels and mRNA expression for interleukin 1 beta (IL-1β), tumour necrosis factor alpha (TNF-α), interleukin 17A (IL17A) and inducible of nitric oxide synthase (iNOs), and p65 protein phosphorylation (NF-κB) were analysed 4 h after pleurisy induction. Animals pre-treated with CE, BuOH, Aq, SA, or LA inhibited leukocytes, exudation, MPO and ADA activities, NO _x , IL-1β, TNF-α, and IL-17A levels, and the mRNA expression for IL-1β, TNF-α, IL-17A, iNOS, and p65 protein phosphorylation (NF-κB) (p < 0.05). Our study demonstrated that J. sellowii can protect against inflammation induced by Cg by decreasing the leukocytes and exudation. Its effects are related to the decrease of either proinflammatory cytokines and/or NO _x . The isolated compounds SA and LA may play an important role in this anti-inflammatory action by inhibiting all the studied parameters. The anti-inflammatory properties of these compounds are due to the downregulation of NF-κB.     

Antitumoural effect of Synadenium grantii Hook f. (Euphorbiaceae) latex

Ethnopharmacological relevance

Synadenium grantii Hook f. has traditionally been used to treat various neoplastic diseases in southern Brazil.

Aim of study

Evaluation of the antitumoural potential of Synadenium grantii latex against B16F10 melanoma cell line using in vitro and in vivo models, as well as a phytochemical study of the latex.

Materials and methods

The in vitro antitumoural activity was performed using MTT and trypan blue assays with different latex concentrations (1.7 µg–7.0 µg/well and 1.22 mg–4.88 mg/well). Flow cytometry was used to determine the progression of the cell cycle. The in vivo activity was performed by subcutaneously injecting melanoma cells in the dorsum of C57BL6 mice, followed by treating the mice with a popular form of use of the latex (garrafada) administered orally. After sacrificing the animals, histological analysis of the organs was performed by hematoxylin-eosin staining. The phytochemical study of the latex was performed by NMR and chromatographic procedures and the extracts and isolated substances were evaluated by IR, 1D and 2D NMR analysis.

Results

The Synadenium grantii latex exhibited decreased cell viability of the melanoma line in a concentration and time-dependent manner, and also cell cycle arrest in the S-G2/M phase. The latex caused a 40% reduction in the volume of tumours of the mice with melanomas. Histological examination of the organs of these animals showed no differences between groups. The phytochemical investigation resulted in the isolation and identification of triterpene euphol and the steroid citrostadienol, which were tested against the strain of melanoma. Euphol showed no antitumoural activity, while the steroid citrostadienol showed reduced cytotoxic activity.

Conclusion

The Synadenium grantii latex presented in vitro and in vivo cytotoxic effects with antitumoural activity against B16F10 melanoma cells.     

Cardiac magnetic resonance imaging and management of dilated cardiomyopathy in a Duchenne muscular dystrophy manifesting carrier

Journal of Neurology -     

Early activation of an altered thyroid hormone profile in asymptomatic or mildly symptomatic idiopathic left ventricular dysfunction

BackgroundAlthough an altered thyroid metabolism has been documented in patients with overt heart failure, no evaluation has been made of a heart-thyroid interaction in mildly symptomatic patients with idiopathic left ventricular dysfunction (ILVD). We wanted to assess the thyroid state in patients with ILVD.Methods and ResultsEighty-six patients (age 60 ± 10 years) were enrolled into the study. Thyroxine (T4), triiodothyronine (T3), thyrotropin, brain and atrial natriuretic peptides (BNP, ANP), noradrenaline, aldosterone, renin activity, and interleukin-6 were measured. Patients were divided into three groups: Group N with LV ejection fraction (EF) ≥50% (n = 28), Group I with LVEF >35%–<50% (n = 34), Group II with LVEF ≤35% (n = 24). There was a significant correlation between T3 and LVEF (r = 0.25, P = .02) and a negative correlation between T3 and BNP (r = –0.37, P < .0001). At univariate analysis T3 was a predictor of LV dysfunction, whereas BNP was the most important predictor at multivariate analysis (P = .002). T3 was the only predictor of New York Heart Association class at multivariate analysis.ConclusionAn altered thyroid profile characterized by a reduction in peripheral production of biologically active T3 is related to LV dysfunction and early symptoms of heart failure in patients with ILVD.     

Aortic elasticity indices by magnetic resonance predict progression of ascending aorta dilation

Objectives

Aortic distensibility and pulse-wave velocity (PWV) are under investigation as parameters by which to evaluate the indication for ascending aorta (AA) replacement. The maximum rate of systolic distension (MRSD) was proposed as a new index of aortic elasticity. The aim of this study was to assess the role of aortic elasticity parameters to predict AA growth rates in patients with AA dilation (AAD).

Methods

Magnetic resonance imaging (MRI) was performed annually in 65 patients with AA dilation (median follow-up 17 months; 25–75th percentile; range 12–30 months). A significant increase in AA diameter was defined as a ≥2-mm increase.

Results

An increase in AA diameter was found in 42 (68 %) patients (AAD+ group) and absent in 20. Median increase was 0.16 (25–75th percentile; range 0.32–0.7) mm/month. The AAD+ group had a lower MRSD (4.6?±?2.2 vs 7.4?±?2.0, p?<?0.001) but the same PWV and distensibility. MRSD showed 93.7 % specificity and 75.6 % sensitivity for prediction of increase. Patients with MRSD?≤?6 had lower progression-free survival times (p?<?0.002). After a follow-up of 4.1 years, patients who underwent surgical therapy had lower MRSD and distensibility than others.

Conclusions

MRSD is an index of aorta elastic properties and is a valuable predictor for progression in AAD.

Key Points

? MRI-derived parameters of aortic wall elasticity predict progression of ascending aorta dilation. ? Maximal rate of systolic distension (MRSD) was the best predictor of progression. ? Patients with MRSD?≤?6 had lower progression-free survival (PFS) times. ? Patients who underwent surgical therapy had lower MRSD and distensibility. ? MRI-derived parameters identify patients with fast progression of Ascending Aorta Dilation.

     

Diterpenoids from Copaifera reticulata Ducke with larvicidal activity against Aedes aegypti (L.) (Diptera, Culicidae)

The objective of this study was to evaluate the larvicidal activity of diterpenoids obtained from the oil-resin of Copaifera reticulata against Aedes aegypti larvae, the principal vector of dengue and urban yellow fever. Four diterpenes were obtained from oil-resin extraction with organic solvents and subsequent chromatographic and spectroscopic procedures allowed to isolation and identification of these compounds as 3-beta-acetoxylabdan-8(17)-13-dien-15-oic acid (1), alepterolic acid (2), 3-beta-hidroxylabdan-8(17)-en-15-oic acid (3), and ent-agatic acid (4). Each compound was previously dissolved in dimethylsulphoxide, and distilled water was added to obtain the desired concentrations. Twenty larvae of third instars were placed into plastic beckers, containing the solution test (25 mL), in a five repetitions scheme, and their mortality, indicated by torpor and darkening of the cephalic capsule, was recorded after 48 h. Probit analyses were used to determine lethal concentrations (LC50 and LC90) and their respective 95% confidence intervals. This study showed that only diterpenoids 1 and 2 exhibited larvicidal properties with LC50 of 0.8 ppm and 87.3 ppm, respectively, revealing the former as the most toxic compound against third instars of Ae. aegypti. Therefore, this compound seems to be an interesting source for new metabolite to be exploited.