Cyclophosphamide-induced apoptosis of murine lymphosarcoma cells in vivo

The antitumor action of combination chemotherapy (cyclophosphamide + adriamycin + vincristin + prednisolone) for transplantable nitrosomethylurea-induced lymphosarcoma was studied in male CBA mice. Single injections of the mixture were followed by complete regression of tumors of up to 2 cm in diameter. The effect was shown to be caused by cyclophosphamide (CP) alone, by inducing apoptosis. The other components failed to potentiate the CD effect. Being useless, they are likely to cause harm by contributing to the overall toxic effect of therapy. The nature and duration of CP-induced remission appeared dose-dependent: on day 50 of the administration of 50, 100 and 150 mg/kg body, tumors were detected in 100, 55 and 0% of the animals, respectively. Such means of apoptosis induction as glycocorticoid treatment and ionizing radiation did not cause complete regression.     

Pharmacokinetic profile of recombinant human N-acetylgalactosamine 4-sulphatase enzyme replacement therapy in patients with mucopolysaccharidosis VI (Maroteaux-Lamy syndrome): a phase I/II study

AIM: Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome) is a lysosomal storage disease caused by a deficiency of the enzyme-N-acetylgalactosamine 4-sulphatase (ASB). Enzyme replacement therapy with recombinant human ASB (rhASB) has been studied in a randomized, double-blind, two-dose (0.2 and 1.0 mg/kg/week) phase I/II study (n = 7) followed by an open-label single dose (1.0 mg/kg/week) extension study. We report the pharmacokinetic profile of rhASB and the impact of antibody development. METHODS: Pharmacokinetic analysis was performed at weeks 1, 2, 12, 24, 83, 84 and 96. Infusions were administered over 4 hours using a ramp-up protocol. Plasma ASB and rhASB antibody concentrations and urine glycosaminoglycan (GAG) concentrations were determined. RESULTS: The area under the plasma concentration-time curve (AUC(0-t)) for the high-dose group increased from week 1 to week 2, but remained unchanged at weeks 12 and 24. A large difference in mean AUC(0-t) was observed between the low- and high-dose groups. Pharmacokinetic results at weeks 83, 84 and 96 were similar to those at week 24. Six patients developed antibodies to rhASB. One patient developed high antibody levels in combination with a high ASB concentration, while a second patient also developed high antibody levels with undetectable ASB concentrations. Antibodies from the second patient blocked detection of ASB. By week 72, antibody levels had decreased in all patients. The high-dose rhASB produced a more rapid and greater percentage reduction in urinary GAG concentrations than the lower dose (70% versus 55% at 24 weeks). Antibody levels did not appear to influence urinary GAG concentrations. CONCLUSION: Pharmacokinetic parameters appear to be independent of the duration of treatment and are not linear between the 0.2 and 1.0 mg/kg/week doses. Antibodies to rhASB develop in most patients, but their concentration decreases over time. Antibody formation may influence pharmacokinetic parameters during the early phases of treatment, although it appears to have limited impact on biochemical efficacy.     

Thirteen-year prospective study between fish consumption,long-chain N-3 fatty acids intakes and cognitive function

Objectives  

Because of their structural, anti-inflammatory and antithrombic properties, longchain n-3 fatty acids may be key factors in the aging process. We sought to elucidate the association between intake of long-chain n-3 fatty acids and/or fish and cognitive function evaluated 13 years after dietary assessment.     

Consumption of dairy products and cognitive functioning: Findings from the SU.VI.MAX 2 study

Objectives

Research concerning the link between dairy product intake and cognition is scant while experimental studies suggest links through various biological mechanisms. This study’s objective was to examine the cross-time associations of total and specific dairy product consumption with cognitive performance in aging adults. We also explored compliance with dairy intake recommendations in France.

Design

The study was based on the «Supplémentation en Vitamines et Minéraux Antioxydants» randomized trial (SU.VI.MAX, 1994-2002) and the SU.VI.MAX 2 observational follow-up study (2007-2009).

Setting

A general-population cohort in France.

Participants

N=3,076 participants included in both the SU.VI.MAX and SU.VI.MAX 2 studies.

Measurements

Dairy product consumption was estimated using repeated 24h records (1994-1996; mean=10 records, SD=3). Cognitive performance was assessed by neuropsychologists after an average of 13 years post-baseline via a battery of six validated tests. Mean age at the time of the cognitive function evaluation was 65.5 (SD=4.6) years. Principal component analysis revealed factors for verbal memory and working memory. Associations of energy-adjusted dairy product consumption and compliance with the respective dietary guidelines with subsequent cognitive impairment were examined using ANCOVA, providing mean differences (95% confidence intervals, CI) according to tertiles (T), adjusted for confounders including overall dietary patterns.

Results

Total dairy product consumption was not associated with cognitive function. However, milk intake was negatively associated with verbal memory performance: mean difference T3 versus T1= -0.99 (-1.83, -0.15). Among women, consuming more than the recommended amount of dairy was negatively associated with working memory performance: excess versus adequate = -1.52 (-2.93, -0.11).

Conclusion

Our results indicate that dairy products consumption and especially compliance with dietary guidelines regarding dairy product intake are differentially associated with performance in specific cognitive domains after a comprehensive adjustment for lifestyle factors, health status markers and dietary patterns. Further longitudinal research is needed given the limited data available.

     

提高孕产期保健质量是降低贫困地区壮族妇女孕产妇死亡的有力措施

目的 :提高贫困地区壮族农村住院分娩率 ,加强产时保健 ,提高贫困地区壮族农村产科质量 ,降低产后出血死亡率。在广西 30个老少边山穷地区 ,以项目和“母亲安全工程”为载体 ,在经济条件困难 ,基础设施落后 ,围产保健服务管理滞后的情况下 ,积极贯彻落实《母婴保健法》,依法规范围产保健服务管理 ,多方筹措资金 ,加强产科软、硬件建设 ,以项目工作为龙头 ,以科研为先导 ,积极推广适宜技术。以健康促进为目的 ,大力开展健康教育和生殖保健活动 ,使围产保健工作取得了较好成绩。30个贫困地区壮族农村近半数以上乡卫生院产科建设已达自治区标准 ,基本能满足贫困地区农民住院分娩的需求 ,并带动广西妇幼卫生工作的发展     

Cyclooxygenase-2--specific inhibitors and cardiorenal function: a randomized, controlled trial of celecoxib and rofecoxib in older hypertensive osteoarthritis patients

BACKGROUND: Arthritis and hypertension are common comorbid conditions affecting elderly adults. Use of nonsteroidal anti-inflammatory drugs in patients treated with antihypertensive medication can lead to destabilization of blood pressure control and other cardiorenal events. The potential for similar interactions with cyclooxygenase-2-specific inhibitors has not been fully explored. The authors evaluated the cardiorenal safety of two new cyclooxygenase-2-specific inhibitors, celecoxib and rofecoxib.METHODS: This study was a 6-week, randomized, parallel-group, double-blind trial in patients with osteoarthritis who were > or =65 years of age and were taking antihypertensive agents. Patients received once-daily celecoxib 200 mg or rofecoxib 25 mg. The primary endpoints were the development of edema, changes in systolic blood pressure, and changes in diastolic blood pressure as measured at any time point in the study. Measurements occurred at baseline and after 1, 2, and 6 weeks of treatment. FINDINGS: Eight hundred ten patients received study medication (celecoxib, n = 411; rofecoxib, n = 399). Nearly twice as many rofecoxib- compared with celecoxib-treated patients experienced edema (9.5% vs. 4.9%, P = 0.014). Systolic blood pressure increased significantly in 17% of rofecoxib- compared with 11% of celecoxib-treated patients (P = 0.032) at any study time point. Diastolic blood pressure increased in 2.3% of rofecoxib- compared with 1.5% of celecoxib-treated patients (P = 0.44). At week 6, the change from baseline in mean systolic blood pressure was +2.6 mmHg for rofecoxib compared with -0.5 mmHg for celecoxib (P = 0.007). CONCLUSIONS: Patients taking antihypertensive therapy and receiving cyclooxygenase-2-specific inhibitors should be monitored for the development of cardiorenal events. Patients receiving celecoxib experienced less edema and less destabilization of blood pressure control compared with those receiving rofecoxib.     

Metabolism inhibition stimulates, metabolism activation inhibits cancerogenic activity of ortho-aminoazotoluene in mouse liver

Pentachlorophenol, an inhibitor of metabolic activation of aminoazo dyes was administered to suckling mice prior to o-aminoazotoluene (OAT). It was followed by formation of numerous preneoplastic nodules and tumors in the lungs and liver. At the same time, 2,3,7,8-tetrachlorodibenzo-p-dioxine treatment decreased their number in the liver while slightly increasing them in the lung. A possible mechanism of aminoazo dye carcinogenicity is suggested.