人体液中喷布洛尔及其代谢物的GC/MS分析

用气相色谱一质谱联用(GC-MSD)系统分析方法检出了人尿中喷布洛尔的6个羟化代谢物,用Scp-Pak柱提取的方法检出了人血浆中的原型药物。并从分子结构上对此药物的代谢途径进行了研究。尿中提取和血中提取的回收率分别为90.83.%和85.88%,Gc-MSD的检测限为5pg。本方法适用于运动员兴奋剂的系统检查。     

The Genotoxic Potential of Linear Alkylbenzene Mixtures in a Short-Term Test Battery

Alkylate 215 (A-215), Alkylate 225 (A-225), and Alkylate 230(A-230) are mixtures of C₁₀–C₁₄ linear alkylbenzenes usedas intermediates for the manufacture of detergents. These productswere evaluated for genotoxic activity in the Ames bacterialmutagenesis assay (strains TA98, 100, 1535, and 1537), the CHO/HGPRTmammalian cell forward gene mutation assay, and the in vivorat bone marrow chromosome assay. The Ames and CHO/HGPRT assayswere conducted both with and without the addition of Aroclor-inducedrat liver S9. The maximum concentrations evaluated were 10 mg/plate(A-215) and 3 mg/plate (A-225 and A-230) for the Ames test,and 1.5 mg/ml (A-215 and A-225) and 2.0 mg/ml (A-230) for theCHO/HGPRT assay. In each case, the highest concentrations producedevidence of either toxicity or insolubility. The highest dosein the bone mar row cytogenetics assay was 12,700 mg/kg, a levelwhich produced significant weight loss. The results of all testswere negative, indicating a lack of genotoxic activity as measuredby the battery of tests used.     

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.      

Presence of the AZF region in a female with an idic(Y)(q11)

In a child with some features of Turner's syndrome, gonosomal mosaicism with an isodicentric nonfluorescent (idic)Y chromosome was detected (mos 45,X/47,X,idic(Y)(q11),idic(Y)(11)/46,X,idic(Y)(q11)). Histopathological examination showed streak gonads with some evidence of ovarian stroma and no sign of gonadoblastoma. Polymerase chain reaction (PCR) analysis in blood lymphocytes and gonadal tissues using primers of seven loci along the Y chromosome, including the sex determined region (SRY), azoospermia factor region (AZF) and the deleted in azoospermia ( DAZ ) gene was positive for all loci tested, confirming the isodicentric character of the Y chromosome and indicating the presence of the AZF region. It is remarkable that the existence of spermatogenesis controlling genes does not play an important role in gonadal development and differentiation in a phenotypic female with some Turner stigmata. The data presented here are briefly discussed with previously-described patients.     

RENAL TRANSPLANTATION – AN EARLY EXPERIENCE

Renal transplant (RT) is now a therapy of choice for end stage renal disease (ESRD). The Nephrology Unit, Asvini started functioning in Dec 90 and to date 1298 sittings of hemodialysis have been given to 45 patients. Of these, 35 were in ESRD and 11 patients underwent renal transplantation at this hospital during the period Jan 91 – Dec 93. One patient expired after 18 months of transplantation due to infection. Early experience in screening patients for RT, use of immunosuppression, management of rejection episodes and protocol are presented with special emphasis on its relevance to the Armed Forces.KEY WORDS: Transplantation, Renal Failure, Immunosuppression, Rejection     

Toxicity of Calcium Sodium Metaphosphate Fiber: I. In Vitro and in Vivo Degradation and Clearance Studies

In an experiment to ascertain the degradability of calcium sodiummetaphosphate (CSM) fiber in vitro, ³²P-labeled CSM fiber wasincubated in media with or without rat lung epithelial cells(LEC) or rat alveolar macrophages (RAM). The amount of radioactivityappearing in the filtrate of the media in the presence of cellsminus the radioactivity in the media in the absence of cellswas considered to reflect cell-aided dissolution of the fiber.LEC and RAM cells increased the degree of dissolution two- andsevenfold, respectively, compared to their respective mediacontrols in a 7-day time period. In a separate experiment, maleFischer rats were given ³²P-labeled CSM fiber either by intraperitonealinjection or by intratracheal instillation and the amount ofradioactivity appearing in the urine and feces was measuredover a period of 60 days. Selected animals from this experimentwere also subjected to whole-body autoradiography 0, 1, 5, 15,30, and 60 days postexposure. After intraperitoneal injection,approximately 0.9% of the administered dose appeared in theurine. A similar percentage of the dose was eliminated in theurine when the fibers were administered by intratracheal instillation;however, the amount of radioactivity in the feces after intratrachealinstillation, i.e., 11.6% of the administered dose, was muchhigher than that after intraperitoneal dose, i.e., 0.24% ofthe administered dose. Whole-body autoradiographs showed a time-relatedincrease in radioactivity at a site other than the site of administration,and the location of this radioactivity appeared to be exclusivelyassociated with mineralized tissue. The clearance of nonradiolabeledCSM fiber (approximately 200,000 fibers) from rat lung afterintratracheal inhalation (IH) and intratracheal instillation(IT) was monitored. Approximately 93% of the initial fiber loadafter IH and approximately 84% of the initial fiber load afterIT was cleared from the lung in 6 months. Histological and biochemicalevaluation of the rat lungs did not reveal any indication offibrosis up to a period of 6 months. All the studies discussedindicate that CSM is de-gradable in biological systems and iscleared from the lung after IT and IH administration. Theseattributes of CSM fiber should reduce the potential for chronicadverse effects in the lung after inhalation.