正常人口服磷酸川芎嗪的药代动力学研究

本文建立了用高效液相色谱法测定人体内川芎嗪血药浓度的方法,以C18化学键合硅胶(10μgm)为固定相,以甲醇—水(58:42)为流动相,280 nm俭测,安眠酮为内标,进行定量测定,得出俭测限为3.5 ng(S/N=4),最低检测血清浓度为17.4 ng/ml,川芎嗪血药浓度在0.029～5.82μg/ml范围内,线性关系良好,方法回收率为99.84%。方法重现性好,专一性强,内源性物质、代谢产物及同时服用的药物均不干扰。用本法测定了健康人口服川芎嗪的药代动力学参数。     

Role of TNF block genetic variants in HIV-associated sensory neuropathy in black Southern Africans

HIV-associated sensory neuropathy (HIV-SN) is a common neurological complication of HIV infection. The TNF block is a region within the central MHC that contains many immunoregulatory genes. Polymorphisms and haplotypes of the TNF block have been associated with increased risk of HIV-SN in Asians and whites. Here we investigated genetic associations with HIV-SN in 342 black Southern Africans (190 cases and 152 neuropathy-free controls) using single nucleotide polymorphisms (SNPs) spanning the TNF block and a set of haplotypes defined by 31 SNPs in Asian and white populations (denoted FVa). We included population-appropriate tagSNPs derived from an African population (Yoruban, YRI, HapMap) and derived extended haplotypes comprising 61 SNPs (denoted FVa_ext b). We found no association between HIV-SN and carriage of two SNPs (TNF-1031/rs1799964*C and BAT1 (intron10)/rs9281523*C) associated with HIV-SN in whites and Asians. Additionally, a haplotype containing TNF-1031/rs1799964*C associated with increased risk of HIV-SN in Asians, but was not present in this African population. However, alleles of seven SNPs associated with reduced risk of HIV-SN (corrected for age, height and multiple comparisons). These were rs11796*A, rs3130059*G, rs2071594*C, NFKBIL1-62/rs2071592*A, rs2071591*A, LTA+252/rs909253*G, rs1041981*C. One haplotype (FV18_ext1), not containing these alleles, was associated with increased risk of HIV-SN after correction for age, height and multiple comparisons. Our results confirm the involvement of genes in the TNF block in altering risk for HIV-SN, but genotypes critical in this African population differed from those affecting HIV-SN in whites and Asians. These differences support the need for genetic association studies in diverse populations.     

抗痫灵在大鼠肝脏中代谢的研究

用离体大鼠肝脏灌流法,研究了抗痫灵在肝脏灌流过程中的代谢规律。用高效液相色谱法由灌流液中分离、制备得到了两种代谢物,经紫外吸收光谱与质谱鉴定,确定代谢物的结构为3,4-次甲基二氧桂皮酰羟基哌啶及阿魏酰哌啶,后者经化学合成得到了进一步的确证。本文还研究了肝循环过程中抗痫灵的代谢动力学,揭示了大部份抗痫灵以原形结合贮存于肝脏中。     

Understanding Malignancies of the Thyroid Gland: Institutional Experience

To study the epidemiological, pathological characters and determine survival in patients diagnosed of having thyroid gland malignancies. Retrospective chart review of patients having thyroid gland malignancies, which were managed by the two senior authors at our tertiary care institute from January 2000 to December 2006, were performed and evaluated in terms of various clinical, operative and histological parameters. Patients in which follow up of at least 10 years are available were included in the study. Survival was enquired telephonically in those patients who got cured and did not consent to come for follow up. Slides were reviewed. Statistical analysis was done using SPSS statistical software. Kaplan–Meier method was used for calculating survival. A total of 182 patients were included in the study. Papillary carcinoma was the commonest malignant lesion with a frequency of 87.91% followed by follicular carcinoma (7.69%), medullary carcinoma (3.29%) and anaplastic carcinoma (1.09%). Female predominance was seen (F:M–5.06:1). The 5 year and 10 year survival rates were 89% and 73% respectively. The most common postoperative squeal was transient hypocalcaemia, seen in (27/182) 15% patients which was followed by permanent hypocalcaemia 16/182 (8.79%), transient recurrent laryngeal nerve paresis 12/182 (6.59%) and permanent recurrent laryngeal nerve palsy 8/182 (4.39%). Thyroid malignancies affect all age groups and have good long term prognosis. Management yields promising results and hence early and adequate treatment is emphasized.     

S100β upregulation: A possible mechanism of deltamethrin toxicity and motor coordination deficits

Deltamethrin (DLT) is a type II synthetic pyrethroid with insecticidal properties. It has been considered safe to humans. Excessive exposure of DLT is being variously reported, recently, to cause potential neurotoxicity in adults, as characterized by ataxia, loss of coordination, hyperexcitability, convulsions and paralysis. However, limited information is available on its impact at lower/safe to human doses during development. The present study was designed to assess the postnatal (P) exposure of DLT (as low as 0.7 mg/kg, i.p.) on S-100β expression in developing rat cerebellum and its impact on Purkinje cell morphogenesis and dendritogenesis, and subsequent spontaneous motor activity (SMA) deficits. Wistar rat pups born to healthy mothers were injected with DLT (Sigma) at a dosage of 0.7 mg/kg body wt., i.p. dissolved in DMSO (Sigma) during P0–7th (DLT-I) and P9–13th day (DLT-II). The control pups were injected with equivalent volumes of DMSO. The pups of both the groups were used to assess the spontaneous motor activity P21 onwards. The cryocut sections (30 μm) of the cerebella were used for anti-S-100β antibody labeling using streptavidin biotin HRP method. An upregulation of S-100β expression in Bergmann glial fibers was recorded at P12 and P15 day preparations in both DLT-I and DLT-II treated groups. However, such upregulation of S-100β was more prominent in DLT-II treated group animals with a large number of strongly S-100β immunopositive astrocytes flanking around the Purkinje neurons. In Golgi preparation the Purkinje neurons in DLT treated groups had reduced dendritic arbor with short primary dendrites and much reduced dendritic branches which appeared stumpy and hypertrophied. The granule cell proliferation and migration as well as Purkinje cell morphogenesis and dendritogenesis are affected following DLT exposure in the present investigation. This may also affect the mossy fiber-granule cell-parallel pathway formation which in turn may decrease the firing of Purkinje cells (GABAergic inhibitory projections) and thus an increase in the output of the neurons in the deep cerebellar nuclei neurons and disturbed motor coordination.     

Jejunal access loop cholangiogram and intervention using image guided access

Jejunal access loop is fashioned in patients who undergo Roux en Y hepaticojejunostomy and biliary intervention is anticipated on follow up. Post-operative study of the biliary tree through the access loop is usually done under fluoroscopic guidance. We present a series of 20 access loop cholangiograms performed in our institution between August 2004 and November 2008. We aimed to evaluate the safety and efficacy of the procedure and to highlight the role of CT guidance in procuring access. Access loop was accessed using CT (n = 13), ultrasound (n = 3) or fluoroscopic guidance (n = 4). Fluoroscopy was used for performing cholangiograms and interventions. Twelve studies had balloon plasty of the stricture at anastomotic site or high up in the hepatic ducts. Seven studies showed normal cholangiogram. Plasty was unsuccessful in one study. Technical success in accessing the jejunal access loop was 100%; in cannulation of anastomotic site and balloon plasty it was 95%. One case required two attempts. Procedure-related complications were not seen. All patients who underwent balloon plasty of the stricture were doing well for variable lengths of time. Access loop cholangiogram and interventions are safe and effective. CT guidance in locating/procuring the access loop is a good technique.     

MicroRNA-132, miR-146a,and miR-155 as potential biomarkers of methotrexate response in patients with rheumatoid arthritis

Clinical Rheumatology - Rheumatoid arthritis (RA) patients have high expression levels of hsa-miR-132-3p, hsa-miR-146a-5p, and hsa-miR-155-5p in peripheral blood. We studied if baseline blood...