Bioactive Steroid from the Root Bark of Psorospermum corymbiferum

AIM:To isolate,characterize and investigate the antifungal activity of the root bark of Psorospermum corymbiferum(Clusiaceae).METHODS:The finely ground root bark of Psorospermum corymbiferum was cold-extracted by percolation with 98% ethanol(5.0 L) for two weeks.The ethanol extract was macerated with n-hexane,chloroform,ethylacetate and methanol successively to give the respective solvent extracts.Fractionation of the extract was done using column chromatography on silica gel with cyclohexene:ethylacetate(1...     

Involvement of endogenous opioid system in scorpion toxin-induced antinociception in mice

The present study analyzes the involvement of the endogenous opioid system in the antinociceptive effects produced in mammals after α- or β- scorpion toxin injections. The analgesic effects on mice of the α-anatoxin Amm VIII, a weak modulator of Na_v1.2 channel, and the depressant insect-selective β-toxin LqqIT2 were evaluated by intraperitoneal route. The two toxins increased hot plate and tail flick latencies in a dose-dependent manner. We also compared the effects of the toxins with those obtained after acetic acid administration or cold-water tail immersion, which both induce pain relief through the activation of diffuse noxious inhibitory controls (DNIC) and the release of endogenous opioids. The increased latencies obtained with the toxins, acetic acid, or cold-water tail immersion were partly reversed by the co-administration of the opioid receptor antagonist naloxone. Finally, AmmVIII, LqqIT2, or acetic acid, induced increased c-fos mRNA expression in spinal cord. This increase disappeared when the toxins were co-injected with acetic acid. In conclusion, we show for the first time that an α-anatoxin exhibits a potent analgesic activity and confirm that depressant β-toxins are able to reduce nociception. We hypothesize that pain relief induced by these scorpion toxins may implicate the activation of an endogenous opioid system and may be partly the result of a counter irritation phenomenon, which could be due to the activation of DNIC.     

Full characterization of three toxins from the Androctonus amoreuxi scorpion venom

In this study, we have characterized the immunological and pharmacological properties of the three major α-type toxins from the scorpion Androctonus amoreuxi, AamH1, AamH2 and AamH3, which were previously described as putative toxins from cDNAs [Chen, T. et al., 2003. Regul. Pept. 115, 115-121].The immunological tests (ELISA, RIA) have demonstrated that AamH1, AamH2 and AamH3 belong to the immunological groups 3 and 4 of α-type toxins. Analysis of the three toxin effects on currents through rat brain (rNav1.2), rat muscle (rNav1.4) and Drosophila (DmNav1) sodium channels expressed in Xenopus oocytes revealed that AamH1 and AamH2, but not AamH3, have anti-insect and anti-mammal activities and can be classified as α-like toxins. While AamH1 removes fast inactivation only in neuronal rNav1.2 channel and has no effect on muscular rNav1.4 channel, AamH2 affects both neuronal rNav1.2 and muscular rNav1.4 channels. AamH3 was lethal to mice by intracerebroventricular injection despite its lack of activity on the neuronal rNav1.2 channel. Finally, we have shown that the A. amoreuxi venom was better neutralized by the antiserum raised against the venom of Buthus occitanus tunetanus than by the antisera raised against scorpion venoms from the same genus Androctonus.     

Natural allelic variants of bovine ATP-binding cassette transporter ABCG2: increased activity of the Ser581 variant and development of tools for the discovery of new ABCG2 inhibitors

ATP-binding cassette transporter ABCG2 [breast cancer resistance protein (BCRP)] is a member of the ABC transporter superfamily that actively extrudes xenotoxins from cells and is a major determinant of the bioavailability of many compounds. ABCG2 expression is strongly induced during lactation in the mammary gland and is related to the active secretion of drugs into the milk. The presence of drug residues and environmental pollutants in milk is an outstanding problem for human milk consumption and milk industrial processes, involving important risks to public health and the dairy industry. In cows, a single nucleotide polymorphism (SNP) in this protein has been described previously (Tyr581) and is associated with higher fat and protein percentages and lower milk yield. However, whether this amino acid substitution affects ABCG2-mediated drug transport in cows, including milk secretion, required further exploration. We cloned the two variants of bovine ABCG2 and evaluated the effect of this SNP on mitoxantrone accumulation assays performed in ovine primary fibroblasts transiently expressing either of the variants. It is interesting to note that statistically significant differences in activity between both variants were observed, and the Ser581 variant was related with an increased efflux activity. In addition, we demonstrated that genistein is a very good inhibitor of bovine ABCG2 and identified new inhibitors of the transporter, such as the macrocyclic lactones, ivermectin, and selamectin. Moreover, the inhibitory effect of these compounds on human and murine ABCG2 homologs was confirmed using transduced Marbin-Dabin canine kidney II cells. These findings may have important implications regarding the presence of drug residues in milk and drug interactions affecting the pharmacological behavior of ABCG2 substrates.     

Health-related quality of life of Southern Chinese with chronic hepatitis B infection

Background  

Few studies have evaluated the health-related quality of life (HRQOL) of Southern Chinese with chronic hepatitis B (CHB) infection.     

Occlusive and reperfused myocardial infarcts: differentiation with Mn- DPDP--enhanced MR imaging

To assess whether the administration of manganese N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid (DPDP) permits differentiation between occlusive and reperfused infarcts, the authors subjected rats to either 6 hours of left coronary artery occlusion (n = 13) or 2 hours of occlusion followed by 4 hours of reperfusion (n = 10) before magnetic resonance (MR) imaging. Electrocardiographic-gated T1-weighted images were obtained before and for 1 hour after injection of 400 mumol/kg of Mn-DPDP. On T1-weighted images obtained before injection of Mn-DPDP. no significant differences in signal intensity were observed between normal and infarcted regions. Use of Mn-DPDP permitted delineation of the area of infarction. The pattern of enhancement in the injured zone was different for occlusive and reperfused myocardial infarcts. In rats with occlusive infarcts, In rats with occlusive infarcts, three well-defined zones were seen. Epicardium and endocardium were enhanced, while the midmyocardial zone was hypointense. The midmyocardial signal intensity gradually increased during the 60 minutes after injection. In rats with reperfused infarcts, the injured area was uniformly and intensely enhanced. Histologic examination confirmed the presence and location of myocardial infarct. Mn-DPDP may improve the detection and delineation of acute myocardial infarcts, demonstrate perfusion of the infarct, and permit discrimination between reperfused and occlusive infarcts.