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...     

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.     

煅烧骨的安全性

背景：经高温处理的煅烧骨具有类似自然骨的连续微孔结构,良好的生物相容性和降解性。 目的：观察牛煅烧骨的生物相容性、细胞相容性及毒性。 方法：①细胞相容性实验：将牛煅烧骨与第3 代已诱导的Wistar大鼠骨髓间充质干细胞复合培养。②溶血实验：将煅烧骨浸提液、生理盐水与双蒸水加入兔血中。③凝血实验：将煅烧骨加入兔血浆中。④急性毒性实验：在昆明种小鼠尾静脉分别注射煅烧骨浸提液、生理盐水。⑤微核实验：在小鼠腹腔分别注射煅烧骨浸提液、生理盐水与环磷酰胺。⑥局部刺激性实验：将煅烧骨浸提液、生理盐水分别注射于兔两侧脊柱皮下。⑦热源检测实验：在兔耳静脉注射煅烧骨浸提液。⑧皮下植入实验：将煅烧骨材料植入Wistar大鼠背部皮下。 结果与结论：煅烧骨材料无细胞毒性,具有良好的细胞及血液相容性;对皮肤、肌肉无刺激作用;对心、肝、肾重要器官无毒性作用;皮下植入后对周围组织无刺激作用,能够部分降解吸收并被机体组织替代;无致热作用,对凝血功能无影响,对小鼠骨髓细胞无抑制及毒性作用。     

Oligoasthenospermia associated with multiple mitochondrial DNA rearrangements

A patient who wished to be treated for infertility by intracytoplasmic sperm injection (ICSI) was referred to our group for assessment. Upon clinical examination, a ptosis (partial closure of the eyelid) was noted, and histology revealed ragged red fibres in the skeletal muscle. Southern blot analysis of spermatozoa and skeletal muscle revealed the presence of multiple mitochondrial DNA deletions. This kind of rearrangement may be of nuclear origin since three nuclear loci have been ascribed to multiple mitochondrial DNA deletions in humans. Since mitochondrial DNA is maternally transmitted, the use of ICSI was feasible. However, an alteration of nuclear gene product affecting the integrity of mitochondrial DNA, and thus sperm mobility, might be transmitted to the offspring with the risk of developing a mitochondrial DNA disease.      

Superiority of newly developed vaginal suppositories over vaginal use of commercial bromocriptine tablets: a randomized controlled clinical trial

The objective of this study is to verify the safety and efficacy of new vaginal bioadhesive suppositories as compared with vaginal use of commercial bromocriptine tablets in hyperprolactinemic patients. This study is a randomized, double-blind, active comparator clinical trial in which a subset of patients had some pharmacokinetic measurements. The setting was an outpatient private infertility clinic in a developing country, and the subjects were 171 patients with hyperprolactinemia. A pilot phase comprised 32 patients who were divided into 2 groups. Group A comprised 16 patients who used vaginal suppositories containing 2.5 mg bromocriptine mesthylate with pluronics and bioadhesive agents once daily for 1 month, while group B included 16 patients who used commercial 2.5-mg bromocriptine mesthylate tablets inserted vaginally once daily for 1 month. The clinical phase comprised 139 patients who were again divided into 2 groups in the same way (group A, 68 patients; group B, 71 patients). Serum prolactin (SP) was measured before and after therapy in all cases. The main outcome measure was the decline of SP level after 1 month of therapy. In both groups, there was a significant decline of the SP. However, it was more significant in group A. Patient convenience was more evident, and local side effects were less in group A than group B in the clinical phase. The introduction of bioadhesive technology for bromocriptine mesylate/pluronic F-126 administration is valuable in achieving prominent serum prolactin reduction in hyperprolactinemic patients in a relatively short duration of therapy. The formulated vaginal suppositories expressed better convenience with minimal local side effects when compared with vaginally administered commercial bromocriptine tablets.     

Proteolytic degradation of von Willebrand factor after DDAVP administration in normal individuals

The infusion of 1-deamino-8-D-arginine vasopressin (DDAVP) in normal individuals is followed by an increase in factor VIII/von Willebrand factor (vWF) in plasma, by an increase in intensity of all sizes of multimers, and by the appearance of larger multimers of vWF than those seen in the resting state. Since the larger multimers are rapidly cleared and proteolysis is known to cause disaggregation of large multimers, we evaluated the degree of vWF proteolysis after DDAVP administration. DDAVP was infused into eight normal adult volunteers, and the relative proportions of the intact 225 kilodalton (kDa) subunit and the 189, 176, and 140 kDa vWF fragments were compared before and at different times after DDAVP infusion. The relative proportion of the 176 kDa fragment was increased, whereas that of the other species was decreased, thereby indicating that proteolytic fragmentation had occurred. However, plasmin did not appear to be responsible because the vWF fragments characteristically produced by this enzyme could not be detected. Concomitant analysis of vWF multimeric structure showed that these changes were accompanied by an increase in the relative proportion of the satellite bands, which suggests that they were proteolytically generated. Proteolysis may explain, at least in part, rapid clearance of larger vWF multimers released by DDAVP.