Plasma protein binding of prednisolone in normal volunteers and arthritic patients

Summary The plasma binding of prednisolone was studied in twenty normal volunteers and twenty rheumatoid arthritis patients. An in vitro assessment of the binding following the addition of prednisolone, prednisone, and hydrocortisone to the plasmas obtained from the subjects showed significant differences in the percentage of prednisolone bound. However, the differences observed were regarded as clinically insignificant. The plasma protein binding was determined by an in vitro equilibrium dialysis of the individual plasma samples at 37° C. Prednisolone levels on both sides of the dialysis membrane were determined using radioactivity and HPLC analytical methodologies. The percentages of prednisolone bound calculated from the analytical results of either the radiochemical or HPLC method were not significantly different. The change in the percentage of prednisolone bound to plasma proteins was studied as a function of the total prednisolone plasma concentration in a normal volunteer and in a systemic lupus erythematosis patient. As a result of prednisolone binding to both transcortin and albumin, the binding of prednisolone changes as a function of prednisolone concentration. The binding data were fitted using nonlinear least squares regression, and the affinity constants for the binding of prednisolone to transcortin and albumin were estimated.     

Bilateral traumatic caroticocavernous fistulae: total resolution following unilateral occlusion

Balloon occlusion is the accepted treatment for direct post-traumatic caroticocavernous fistula. We present a case of bilateral traumatic fistulae associated with a pseudoaneurysm. Resolution of both fistulae occurred following treatment of one of them by balloon occlusion of the internal carotid artery. This case highlights the importance of considering a more conservative approach to bilateral fistulae or those associated with a pseudoaneurysm. We review other treatment options. Received: 1 October 1999/Accepted: 20 October 1999     

磺胺类药物的毛细管高效液相色谱与电色谱研究

目的 研究毛细管高效液相色谱(μ-HPLC)和毛细管电色谱(CEC)分离磺胺类药物,建立药物微分离分析方法。方法 用ODS柱为固定相,甲醇和2 mmol·L^-1磷酸缓冲液（pH 3.0～7.0）为流动相,电压为0～-15 kV,流速为10 μL·min^-1,紫外检测波长254 nm。结果μ-HPLC在甲醇-2 mmol·L^-1磷酸缓冲液（30∶70）,pH 3.0时5种磺胺类药物实现基线分离;CEC在电压为-5 kV,甲醇-2 mmol·L^-1磷酸缓冲液（30∶70）,pH 5.0时5种磺胺类药物实现基线分离。结论电渗流随甲醇含量、缓冲液浓度增加而下降,随pH值、电压的增加而增加;溶质的保留值（k）随甲醇含量、缓冲液浓度、电压的增加而下降,随电压增加下降明显的是TMP,随pH值变化较复杂。在相同条件下对5种磺胺类药物的分离,μ-HPLC需67 min,CEC只需25 min,后者更适合于磺胺类药物的快速分离分析。     

Identification of differentially expressed genes in aflatoxin B1- treated cultured primary rat hepatocytes and Fischer 344 rats

Aflatoxin B1 (AFB1), a mutagen and hepatocarcinogen in rats and humans, is a contaminant of the human food supply, particularly in parts of Africa and Asia. AFB1-induced changes in gene expression may play a part in the development of the toxic, immunosuppressive and carcinogenic properties of this fungal metabolite. An understanding of the-role of AFB1 in modulating gene regulation should provide insight regarding mechanisms of AFB1-induced carcinogenesis. We used three PCR- based subtractive techniques to identify AFB1-responsive genes in cultured primary rat hepatocyte RNA: differential display PCR (DD-PCR), representational difference analysis (RDA) and suppression subtractive hybridization (SSH). Each of the three techniques identified AFB1- responsive genes, although no individual cDNA was isolated by more than one technique. Nine cDNAs isolated using DD-PCR, RDA or SSH were found to represent eight genes that are differentially expressed as a result of AFB1 exposure. Genes whose mRNA levels were increased in cultured primary rat hepatocytes after AFB1 treatment were corticosteroid binding globulin (CBG), cytochrome P450 4F1 (CYP4F1), alpha-2 microglobulin, C4b-binding protein (C4BP), serum amyloid A-2 and glutathione S-transferase Yb2 (GST). Transferrin and a small CYP3A-like cDNA had reduced mRNA levels after AFB1 exposure. Full-length CYP3A mRNA levels were increased. When liver RNA from AFB1-treated male F344 rats was evaluated for transferrin, CBG, GST, CYP3A and CYP4F1 expression, a decrease in transferrin mRNA and an increase in CBG, GST, CYP3A and CYP4F1 mRNA levels was also seen. Analysis of the potential function of these genes in maintaining cellular homeostasis suggests that their differential expression could contribute to the toxicity associated with AFB1 exposure.      

Delivery Complications Associated With Prenatal Care Access for Medicaid-Insured Mothers in Rural and Urban Hospitals

CONTEXT: Pregnancy complications affect many women. It is likely that some complications can be avoided through routine primary and prenatal care of reasonable quality. PURPOSE: The authors examined access to health care during pregnancy for mothers insured by Medicaid. The access indicator is potentially avoidable maternity complications (PAMCs). Potentially avoidable maternity complications are often preventable through routine prenatal care, such as infection screening and treatment. The authors examined the risks of potentially avoidable maternity complications among rural and urban hospital deliveries for groups of mothers defined by race or ethnicity. METHODS: Data are from the year 2000 Nationwide Inpatient Sample (NIS). The stratified sample represents all discharges from 20.5% of community hospitals in the United States. The Nationwide Inpatient Sample identifies hospital locations, but not patients' areas of residence. Analyses, which accounted for the sample design, included calculation of potentially avoidable maternity complication rates by race or ethnicity, chi2, t tests, and multivariate logistic regression. FINDINGS: Within groups defined by race or ethnicity, unadjusted rates for potentially avoidable maternity complications did not differ significantly by hospital location. Holding other factors constant, potentially avoidable maternity complications were less common in rural hospitals than in urban hospitals (odds ratio, 0.78; CI, 0.62 to 0.99). In rural hospitals, African Americans had notably higher risk for potentially avoidable maternity complications than did non-Hispanic whites (odds ratio, 1.72; CI, 1.26 to 2.36). In urban hospitals, risk of potentially avoidable maternity complications was not significantly higher for African Americans. Hispanics and Asians had notably lower risks of potentially avoidable maternity complications in urban hospitals than did non-Hispanic whites. CONCLUSIONS: Providers and policymakers should work to reduce the risks of potentially avoidable maternity complications for African American women in rural areas who are insured by Medicaid.     

Type 1 diabetes: pathogenesis and prevention

Type 1 diabetes results from the autoimmune destruction of insulin-producing β cells in the pancreas. Genetic and, as yet undefined, environmental factors act together to precipitate the disease. The excess mortality associated with the complications of type 1 diabetes and the increasing incidence of childhood type 1 diabetes emphasize the importance of therapeutic strategies to prevent this chronic disorder. Why is it considered that type 1 diabetes might be preventable? Different strands of diabetes research are coming together to suggest therapeutic targets. Islet cell autoantibody assays make it possible to accurately identify people at risk of future disease. In most cases, a long prodrome provides a window of opportunity to reverse the autoimmune process. Although no current “cure” exists, recent genetic data and preliminary trial results suggest T cells as a target for preventive strategies. Another potentially attainable target is induction of tolerance to the β-cell proteins such as insulin that are inappropriately recognized. Other strategies involve β-cell replacement, but currently there are insufficient donor cells available. This may be overcome as the processes controlling the differentiation of pancreatic and nonpancreatic progenitors as well as replication of existing islet β cells are unravelled.