Current Issue : October - December Volume : 2016 Issue Number : 4 Articles : 5 Articles
Background: 3,4-Methylenedioxymethamphetamine (MDMA or ââ?¬Å?ecstasyââ?¬Â) is a worldwide drug of abuse commonly\nused by adolescents. Most reports focus on MDMAââ?¬â?¢s neurotoxicity and use high doses in adult animals, meanwhile\nstudies in adolescents are scarce. We aimed to assess in rats the acute MDMA toxicity to the brain and peripheral\norgans using a binge dose scheme that tries to simulate human adolescent abuse.\nMethods: Adolescent rats (postnatal day 40) received three 5 mg/kg doses of MDMA (estimated equivalent to\ntwo/three pills in a 50 kg adolescent), intraperitoneally, every 2 h, while controls received saline. After 24 h animal\nsacrifice took place and collection of brain areas (cerebellum, hippocampus, frontal cortex and striatum) and\nperipheral organs (liver, heart and kidneys) occurred.\nResults: Significant hyperthermia was observed after the second and third MDMA doses, with mean increases of\n1 Ã?°C as it occurs in the human scenario. MDMA promoted ATP levels fall in the frontal cortex. No brain oxidative\nstress-related changes were observed after MDMA. MDMA-treated rat organs revealed significant histological\ntissue alterations including vascular congestion, but no signs of apoptosis or necrosis were found, which was\ncorroborated by the lack of changes in plasma biomarkers and tissue caspases. In peripheral organs, MDMA did not\naffect significantly protein carbonylation, glutathione, or ATP levels, but liver presented a higher vulnerability as\nMDMA promoted an increase in quinoprotein levels.\nConclusions: Adolescent rats exposed to a moderate MDMA dose, presented hyperthermia and acute tissue\ndamage to peripheral organs without signs of brain oxidative stress....
Background: Olvanil (NE 19550) is a non-pungent synthetic analogue of capsaicin, the natural pungent ingredient\nof capsicum which activates the transient receptor potential vanilloid type-1 (TRPV1) channel and was developed as\na potential analgesic compound. Olvanil has potent anti-hyperalgesic effects in several experimental models of\nchronic pain. Here we report the inhibitory effects of olvanil on nociceptive processing using cultured dorsal root\nganglion (DRG) neurons and compare the effects of capsaicin and olvanil on thermal nociceptive processing in\nvivo; potential contributions of the cannabinoid CB1 receptor to olvanilâ��s anti-hyperalgesic effects were also\ninvestigated.\nMethods: A hot plate analgesia meter was used to evaluate the anti-nociceptive effects of olvanil on capsaicin-induced\nthermal hyperalgesia and the role played by CB1 receptors in mediating these effects. Single cell calcium imaging studies\nof DRG neurons were employed to determine the desensitizing effects of olvanil on capsaicin-evoked calcium responses.\nStatistical analysis used Studentâ��s t test or one way ANOVA followed by Dunnettâ��s post-hoc test as appropriate.\nResults: Both olvanil (100 nM) and capsaicin (100 nM) produced significant increases in intracellular calcium\nconcentrations [Ca2+]i in cultured DRG neurons. Olvanil was able to desensitise TRPV1 responses to further capsaicin\nexposure more effectively than capsaicin. Intraplantar injection of capsaicin (0.1, 0.3 and 1 �¼g) produced a robust TRPV1-\ndependant thermal hyperalgesia in rats, whilst olvanil (0.1, 0.3 and 1 �¼g) produced no hyperalgesia, emphasizing its lack\nof pungency. The highest dose of olvanil significantly reduced the hyperalgesic effects of capsaicin in vivo. Intraplantar\ninjection of the selective cannabinoid CB1 receptor antagonist rimonabant (1 �¼g) altered neither capsaicin-induced\nthermal hyperalgesia nor the desensitizing properties of olvanil, indicating a lack of involvement of CB1 receptors.\nConclusions: Olvanil is effective in reducing capsaicin-induced thermal hyperalgesia, probably via directly desensitizing\nTRPV1 channels in a CB1 receptor-independent fashion. The results presented clearly support the potential for olvanil in\nthe development of new topical analgesic preparations for treating chronic pain conditions while avoiding the unwanted\nside effects of capsaicin treatments....
Extracellular matrix (ECM) components are critical for all aspects of cell proliferation, adhesion,\nand morphological alteration. Recent progress has yielded multiple molecular drugs that specifically\ntarget gene products which are expressed at high levels in tumor cells. We investigated\nwhether the sensitivity of tumor cells to molecular target drugs could be altered when cells were\ncultured on surfaces with various coating conditions such as lysine, laminin, Matrigel, collagen\ntype I, and human fibronectin (HFN). This study evaluates the IC50 values of imatinib in oral\nsquamous cell carcinoma (OSCC) cell lines when cells are cultured on plates coated with ECM\ncomponents such as collagen type I and HFN. Four OSCC cell linesââ?¬â?SQUU-A, SQUU-B, SAS, and NAââ?¬â?\nare used. Cell proliferation was assessed using WST-8 reagent. Collagen type I and HFN significantly\nenhanced OSCC cell proliferation compared with control. Imatinib cytotoxicity was demonstrated\nfollowing culture of OSCCs in culture plates coated with collagen type I or HFN. However,\nthere were no significant changes in imatinib IC50 values between collagen type I and HFN. These\nresults indicate that some molecular target drugs exhibit cancer cell cytotoxicity without being influenced\nby cell environment factors such as the ECM. These results may aid in the search for molecular\ntarget drugs to apply in the clinical chemotherapy of OSCC....
Novel esters of �³-aminobutyric acid (GABA) with monocyclic terpenes were synthesized via\nSteglich esterification and characterized by 1H-NMR, IR and mass spectral studies. Their anticonvulsant,\nanalgesic and anti-inflammatory activities were evaluated by a PTZ-induced convulsion model,\nAITC-induced hyperalgesia and AITC-induced paw edema, respectively. All studied esters, as well\nas their parent terpenes, were found to produce antinociceptive effects in the AITC-induced model\nand attenuate acute pain more than the reference drug benzocaine after their topical application.\nGABA esters of L-menthol and thymol were also shown to exceed the reference drug ibuprofen\nin their ability to decrease the inflammatory state induced by intraplantar injection of the TRPA1\nactivator AITC. The present findings indicate that GABA esters of carvacrol and guaiacol are not a\nclassical prodrug and possess their own pharmacological activity. Prolonged antiseizure action of the\nester based on the amino acid and guaiacol (200 mg/kg) was revealed at 24 h after oral administration.\nFurthermore, orally co-administered gidazepam (1 mg/kg) and GABA esters of L-menthol, thymol\nand carvacrol produce synergistic seizure prevention effects....
Diabetes mellitus (DM) is a health problem affecting millions of individuals worldwide. Diabetic\nnephropathy (DN), as a significant complication of DM, has become the most common cause of endstage\nrenal failure. Oxidative stress constitutes the key and common events in the pathogenesis of\nDN and antioxidants may play a beneficial role in its prevention. This study was conducted to investigate\nthe effect of Zinc Chloride on streptozotocin-induced diabetic nephropathy in rats compared\nto Gliclazide, a reference antidiabetic agent. Results showed that Zinc Chloride was able to\ncontrol STZ-induced DN in rats as it normalized the elevated blood pressure, the increased insulin\nrelease, and the decreased blood glucose level. Zinc Chloride also improved kidney function as\ndetermined by the restoration of blood urea and creatinine level. Finally, Zinc Chloride was able to\nboost the antioxidant defenses of the kidney by increasing the reduced glutathione content and\ndecreasing lipid peroxides content in addition to significantly decreasing kidney nitric oxide content\ncompared to diabetic control rats. These results suggest that exposure to Zinc Chloride can\nprotect from diabetic nephropathy and can be used as an adjuvant approach to treatment and prevention\nof renal damage....
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