KM-34, a Novel Antioxidant Compound, Protects against 6-Hydroxydopamine-Induced Mitochondrial Damage and Neurotoxicity.

The etiology of Parkinson's disease is not completely understood and is believed to be multifactorial. Neuronal disorders associated to oxidative stress and mitochondrial dysfunction are widely considered major consequences. The aim of this study was to investigate the effect of the synthetic arylidenmalonate derivative 5-(3,4-dihydroxybenzylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione (KM-34), in oxidative stress and mitochondrial dysfunction induced by 6-hydroxydopamine (6-OHDA). Pretreatment (2 h) with KM-34 (1 and 10 µM) markedly attenuated 6-OHDA-induced PC12 cell death in a concentration-dependent manner. KM-34 also inhibited H2O2 generation, mitochondrial swelling, and membrane potential dissipation after 6-OHDA-induced mitochondrial damage. In vivo, KM-34 treatment (1 and 2 mg/Kg) reduced percentage of asymmetry (cylinder test) and increased the vertical exploration (open field) with respect to untreated injured animals; KM-34 also reduced glial fibrillary acidic protein overexpression and increased tyrosine hydroxylase-positive cell number, both in substantia nigra pars compacta. These results demonstrate that KM-34 present biological effects associated to mitoprotection and neuroprotection in vitro, moreover, glial response and neuroprotection in SNpc in vivo. We suggest that KM-34 could be a putative neuroprotective agent for inhibiting the progressive neurodegenerative disease associated to oxidative stress and mitochondrial dysfunction.

Evidence for the involvement of descending pain-inhibitory mechanisms in the antinociceptive effect of hecogenin acetate.

Hecogenin is a sapogenin present in the leaves of species from the Agave genus, with a wide spectrum of reported pharmacological activities. The present study was undertaken to evaluate whether hecogenin acetate (1) has antinociceptive properties and to determine its mechanism of action. The nociceptive threshold was evaluated using the tail flick test in mice. Mice motor performance was evaluated in a Rotarod test. By using Fos expression as a marker of neural activation, the involvement of the periaqueductal gray in 1-induced antinociception was evaluated. Intraperitoneal administration of 1 (5-40 mg/kg) produced a dose-dependent increase in the tail flick latency time compared to vehicle-treated group (p < 0.01). Mice treated with 1 (40 mg/kg) did not show motor performance alterations. The antinociception of 1 (40 mg/kg) was prevented by naloxone (nonselective opioid receptor antagonist; 5 mg/kg), CTOP (µ-opioid receptor antagonist; 1 mg/kg), nor-BNI (κ-opioid receptor antagonist; 0.5 mg/kg), naltrindole (δ-opioid receptor antagonist; 3 mg/kg), or glibenclamide (ATP-sensitive K(+) channel blocker; 2 mg/kg). Systemic administration of 1 (5-40 mg/kg) increased the number of Fos positive cells in the periaqueductal gray. The present study has demonstrated for the first time that 1 produces consistent antinociception mediated by opioid receptors and endogenous analgesic mechanisms.

Anti-inflammatory effects of carvacrol: evidence for a key role of interleukin-10.

Carvacrol, a phenolic monoterpene, has been reported to possess anti-inflammatory properties. However, the mechanisms involved in its pharmacological properties are currently not well understood. In the present study, the contribution of cytokine modulation to the anti-inflammatory effects of carvacrol was investigated in a classical inflammation model: the complete Freund's adjuvant (CFA)-induced paw inflammation in mice. The paw edema was measured using a plesthismometer. Paw tissue was removed 2h after the inflammatory stimulus to determine the levels of prostaglandin E(2) (PGE(2)) by enzyme immunoassay, the levels of interleukin-1 ß (IL-1ß), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) by ELISA or the mRNA expression of cyclooxygenase-2 (COX-2), IL-1ß, TNF-α, and IL-10 by real-time PCR. Administration of carvacrol produced anti-inflammatory effects against CFA-induced inflammation in mice. Treatment of mice with carvacrol at 50 and 100mg/kg attenuated the paw edema and reduced the IL-1ß and PGE(2), but not TNF-α, local levels. Similarly, carvacrol (100mg/kg) reduced the COX-2 and IL-1ß mRNA expression. The levels of IL-10, an anti-inflammatory cytokine, and the IL-10 mRNA expression in the inflamed paw were enhanced by carvacrol. In addition, the treatment with carvacrol did not reduce the CFA-induced paw edema in IL-10 knockout mice. The present results suggest that carvacrol causes anti-inflammatory effects by reducing the production of inflammatory mediators, such as IL-1ß and prostanoids, possibly through the induction of IL-10 release.

Assessment of antimicrobial activity and healing potential of mucous secretion of Achatina fulica / Evaluación de la actividad antimicrobiana y la cicatrización potencial de la secreción mucosa de Achatina fulica

Achatina fulica's secretion has been recently related to antibacterial, antifungal, and cicatricial properties, and it is influenced by the kind of food offered. Therefore, this study investigated the healing potential of dressing films based on mucous secretion of Achatina fulica. Thus, surgical wounds performed in black wistar rats were dressed with films based on collagen, and on mucous secretion of A. fulica fed with Lactuca sativa; undresses worked as wounds control. After 3, 7, 14 and 21 days the animals were euthanized, and the wounds were microscopically evaluated. On the 3rd and 7th days dressing films based on mucus provided acceleration of the formation maturation of granulation tissue, better epithelization rates, and more rapid replacement of type III for type I collagen fibers. On the 14th and 21st days, these dressings induced more intense deposition and better architectural disposition of type I collagen fibers, and hastened the regeneration of cutaneous phaneros. Dressings obtained from A. fulica fed with Lactuca sativa provided the most expressive results. This study suggests that films produced with mucous secretion of A. fulica can be successfully employed as wound dressing, particularly if snails are fed with Lactuca sativa.

A la secreción mucoproteica del Achatina fulica se le han asignado propiedades antibacterianas, antifúngicas y cicatriciales que pueden estar influidas por el tipo de alimento que se ofrece a este especimen. Este estudio investigó el potencial curativo de películas basadas en la secreción mucosa de Achatina fulica alimentaba con diferentes tipos de plantas. Fueron tratadas heridas provocadas en el dorso de ratas Wistar con películas de colágeno y películas realizadas a partir de la secreción mucosa de A. fulica, alimentados con plantas de lechuga (L. sativa), utilizando como parámetro de comparación la curación del grupo de control. Después de 3, 7, 14 y 21 días los animales fueron sacrificados y las heridas fueron evaluadas microscópicamente. En los días 3 y 7, las heridas tratadas con moco mostraron mejores tasas de formación y maduración del tejido de granulación, epitelización, y más rápido recambio de colágeno tipos III y I. A los días 14 y 21, hubo una intensa deposición del colágeno tipo I y aceleración en la regeneración de la piel. Los resultados obtenidos a partir de A. fulica alimentados con plantas de lechuga (L. sativa) mostraron mejores resultados. Este estudio sugiere que las películas producidas con secreción mucosa de A. fulica pueden ser utilizadas con éxito como apósito, especialmente si los caracoles se alimentan con plantas de lechuga L. sativa.

Incidence of Entamoeba gingivalis and Trichomonas tenax in samples of dental biofilm and saliva from patients with periodontal disease / Incidência de Entamoeba gingivalis e Trichomonas tenax em amostras de biofilme e saliva de pacientes com doença periodontal

OBJECTIVE: This study analyzed the incidence of Entamoeba gingivalis and Trichomonas tenax in samples of dental biofilm and saliva from patients with gingivitis / periodontitis and in healthy subjects. METHODS: Biofilm and saliva samples were taken from 20 patients with gingivitis, 22 with periodontitis and 9 healthy individuals. They were spread on sterile Petri dishes, diluted with saline and examined with a light microscope. Salivary pH was determined by universal pH indicators trips. The chi-square test was used to determine significance (p<0.05). RESULTS: Almost one-third (31.37 percent) (50 percent from gingivitis and 50 percent from periodontitis) of the biofilm samples and 35.29 percent (39 percent from gingivitis and 61 percent from periodontitis) of the saliva samples were positive for Entamoeba gingivalis. Trichomonas tenax was found in 22.53 percent of the biofilm samples (16.66 percent from gingivitis, 41.67 percent from periodontitis and 41.67 percent from healthy patients) and 9.81 percent of the saliva samples (20 percent from gingivitis, 40 percent from periodontitis and 40 percent from healthy patients).The presence of these microorganisms was related to the type of periodontal disease (p=0.001), but not with age (p=0.178) or risk factors (p=0.194). CONCLUSION: These findings suggest that Entamoeba gingivalis more common in the early stages of periodontitis, while Trichomonas tenax is considered a protozoan of the gingival sulcus. However, further studies are needed to determine the relationship between these species and periodontitis.

OBJETIVO: Analisar a incidência de Entamoeba gingivalis e Trichomonas tenax em amostras de biofilme dental e saliva de pacientes com gengivite/periodontite e de indivíduos saudáveis. MÉTODOS: Amostras de saliva e biofilme foram obtidas de 20 pacientes com gengivite, 22 com periodontite e 9 indivíduos saudáveis. O material foi depositado em placas de Petri e diluído em soro fisiológico para posterior observação. O pH das amostras de saliva foi determinado com fitas indicadoras de pH. Os dados foram tratados por teste qui-quadrado (p<0,05). RESULTADOS: Foi observada positividade para Entamoeba gingivalis em 31,37 por cento das amostras de biofilme (50,00 por cento com gengivite e 50,00 por cento com periodontite) e 35,29 por cento de saliva (39,00 por cento gengivite e 61,00 por cento periodontite). Foi observado o Trichomonas tenax em 22,53 por cento das amostras de biofilme (16,66 por cento gengivite, 41,67 por cento periodontite, e 41,67 por cento saudáveis) e 9,81 por cento de saliva (20,00 por cento gengivite, 40,00 por cento periodontite, e 40,00 por cento saudáveis). A presença de parasitas esteve relacionada ao tipo de doença periodontal (p=0,001), mas não a idade (p=0,178) e a fatores de risco (p=0,194). CONCLUSÃO: Estes achados sugerem que a Entamoeba gingivalis aparece mais em estágios iniciais da periodontite, enquanto que o Trichomonas tenax é considerado um protozoário do sulco gengival. Contudo, outros estudos são necessários para determinar a relação entre essas espécies e a periodontite.