~3H-α-第二丁基对羟基苄醇在家兔体内的药物动力学研究

本文报道给家兔注入不同剂量的~3H-α-第二丁基对羟基苄醇,观察该药在其体内的药物动力学。结果表明,血中分布相快,消除相慢,消除半衰期T_1/1β为12h。经F值检验和理论计算值与实测值的契合程度比较,表明该药在兔体内的运转符合二室开放模型的动力学方程。     

Effects of a monoclonal antibody raised against nerve growth factor on skeletal pain and bone healing after fracture of the C57BL/6J mouse femur.

A closed femur fracture pain model was developed in the C57BL/6J mouse. One day after fracture, a monoclonal antibody raised against nerve growth factor (anti-NGF) was delivered intraperitoneally and resulted in a reduction in fracture pain-related behaviors of approximately 50%. Anti-NGF therapy did not interfere with bone healing as assessed by mechanical testing and histomorphometric analysis. INTRODUCTION: Current therapies to treat skeletal fracture pain are limited. This is because of the side effect profile of available analgesics and the scarcity of animal models that can be used to understand the mechanisms that drive this pain. Whereas previous studies have shown that mineralized bone, marrow, and periosteum are innervated by sensory and sympathetic fibers, it is not understood how skeletal pain is generated and maintained even in common conditions such as osteoarthritis, low back pain, or fracture. MATERIALS AND METHODS: In this study, we characterized the pain-related behaviors after a closed femur fracture in the C57BL/6J mouse. Additionally, we assessed the effect of a monoclonal antibody that binds to and sequesters nerve growth factor (anti-NGF) on pain-related behaviors and bone healing (mechanical properties and histomorphometric analysis) after fracture. RESULTS: Administration of anti-NGF therapy (10 mg/kg, days 1, 6, and 11 after fracture) resulted in a reduction of fracture pain-related behaviors of approximately 50%. Attenuation of fracture pain was evident as early as 24 h after the initial dosing and remained efficacious throughout the course of fracture pain. Anti-NGF therapy did not modify biomechanical properties of the femur or histomorphometric indices of bone healing. CONCLUSIONS: These findings suggest that therapies that target NGF or its cognate receptor(s) may be effective in attenuating nonmalignant fracture pain without interfering with bone healing.     

Risk factors for surgical site infection in children.

OBJECTIVES: To assess the appropriateness of using the indices developed by the Study on the Efficacy of Nosocomial Infection Control (SENIC) and the National Nosocomial Infections Surveillance (NNIS) project to determine risk factors for surgical site infection (SSI) in children and, if not appropriate, to explore the factors related to SSI in children so these factors could be used in a risk index for pediatric patients. DESIGN: Cohort study during more than 4 years. SETTING: La Paz University Hospital, a national reference center that serves Health Area 5 of Madrid, Spain, which has approximately 500,000 inhabitants. PATIENTS: Convenience sample consisting of the 3,646 children admitted for surgery who had a postsurgical stay of more than 2 days. RESULTS: A model with 8 predictive factors (degree of surgical contamination; duration of surgery; type of surgery; use of a peripheral venous catheter, central venous catheter, or urinary catheter; number of diagnoses; and SSI exposition time) was created. Its relation to the SSI rate was better than that of the SENIC or NNIS indices. Its sensitivity, specificity, and area under the receiver-operating characteristic curve were higher than that of the SENIC index. CONCLUSIONS: The model that we created seems to be more adequate for predicting SSI and evaluating pediatric patients' intrinsic risk than the SENIC and NNIS indices.     

Effects of cerulenin on the endogenous fatty acid synthetic activity in squamous cell carcinoma of the oral cavity.

PURPOSES: Inhibition of cerulenin on the endogenous fatty acid synthetic activities of oral squamous cell carcinoma (OSCC) and normal oral mucosa was assayed. METHODS: Squamous cell carcinoma and normal oral mucosa were collected fresh from surgical specimens. The collected tissues were minced in RPMI 1640 and divided into 3 groups: cerulenin treated, dimethylsulfoxide treated, and control. The tissues were incubated in [1(2)-(14)C]acetic acid, sodium salt for the last 2.5 hours of the treatment at 37 degrees C in 5% CO(2). After labeling, total lipids were extracted and counted for (14)C by scintillation counting. RESULTS: Endogenous fatty acid synthetic activities of oral squamous cell caranoma in the cerulenin-treated group decreased by 19% at 1 hour, 64% at 2 hours, and 87% at 4 hours; remained nearly unchanged in the dimethylsulfoxide-treated group; and increased slightly in the control group. The oral mucosa tissues were only mildly affected by cerulenin in fatty acid synthesis. CONCLUSIONS: Cerulenin significantly inhibits fatty acid synthetic activity in squamous cell carcinoma and only mildly affected the oral mucosa, indicating that the fatty acid synthetic pathway may be exploited as a target for developing anticancer drugs.     

Antioxidant and glutathione-related enzymatic activities in rat sciatic nerve

The present work tries to establish the antioxidant capacity of the peripheral nervous tissue of the rat, in terms of the enzymatic activities present in this tissue that either prevent the formation of activated species as the semiquinone radical (DT-diaphorase), protect against activated oxygen species (superoxide dismutase, glutathione peroxidase), conjugate natural toxic products or xenobiotics (glutathione S-transferases, especially the activity conjugating 4-hydroxy-nonenal), or complete the glutathione system metabolism (glutathione disulfide reductase, γ-glutamyl transpeptidase). All the activities studied are lower in this tissue than they are in liver, except for γ-glutamyl transpeptidase. The relevance of the results obtained and its possible relationship with different neuropathies is discussed. It is concluded that the peripheral nervous tissue is by far less protected than the liver against oxidative damage.     

Melatonin reduces nitric oxide synthase activity in rat hypothalamus

Abstract: In this report, rat hypothalamic nitric oxide synthase (NOS) activity is shown to be partially inhibited by physiological concentrations of the pineal hormone melatonin. In vitro studies demonstrate that 1 nM melatonin, which approximates the physiological concentration of the hormone at night, significantly inhibited NOS activity. In vivo studies show that administering melatonin or collecting the hypothalamus from animals at night, when endogenous melatonin levels are elevated, results in a significant decrease of NOS activity. Results also show that calmodulin may be involved in this process since its presence in the incubation medium prevents the inhibitory effect of melatonin on NOS activity.     

Immunology

A selection of interesting papers that were published in the two months before our press date in major journals most likely to report significant results in immunology.     

肠溶阿斯匹林剂量和血阿斯匹林及水杨酸盐浓度与药效关系探讨

本文探讨了ＡＳＡ剂量与药效的关系及血ＡＳＡ、ＳＡ药物浓度监测的临床意义，结果表明：（１）ＡＳＡ剂量与６－ｋｅｔｏ－ＰＧＦ_（１α）抑制率呈正相关（Ｐ＜０．０１），而与ＴＸＢ_２及ＰＡｇＲ抑制率无相关性（Ｐ＞０．１）；（２）本文采用ＨＰＬＣ内标法同时测定血ＡＳＡ和ＳＡ浓度，结果准确，方法简便；（３）当口服小剂量ＡＳＡ防治ＣＩ时，监测血ＡＳＡ和ＳＡ以调整ＡＳＡ用药剂量的临床价值并非十分重要。