Evalutaion of the Gender Differences in 4,4'-Methylenedianiline Toxicity,Distribution, and Effects on Biliary Parameters

Exposure to 4,4'-diaminodiphenylmethane (DAPM) has been linked to jaundice, toxic hepatitis, cholangitis, and cholestasis. In rodents, DAPM initially injures biliary epithelial cells, and toxicity is greater in female than male rats. Our goal was to determine if gender differences in DAPM toxicity were due to differences in biliary excretion or covalent binding of DAPM metabolites in the liver. Bile duct-cannulated female and male Sprague-Dawley rats were gavaged with vehicle or with 25 or 50 mg [¹⁴C]DAPM/kg, and bile was collected for 6 h. Serum and bile indicators of hepatobiliary toxicity were assessed, and radioactivity was measured in bile, serum, urine, and liver. At the 25 mg/kg dose, serum parameters were elevated only in female rats, while increases in serum parameters were observed in both genders at the 50 mg/kg dose. In males rats, biliary constituents altered by DAPM [inorganic phosphate (P_i     

Steroids Alone or as Adjunctive Therapy with Doxycycline Fail To Improve Oviduct Damage in Mice Infected with Chlamydia muridarum

In women, Chlamydia trachomatis can ascend from the cervix to the fallopian tubes, where an overly aggressive host inflammatory response can cause scarring that leads to chronic pelvic pain, infertility, or ectopic pregnancy. Although screening and treatment programs for women have resulted in decreased rates of sequelae, morbidities associated with oviduct scarring continue to occur. Since corticosteroids have anti-inflammatory and antifibrotic effects, we tested the ability of dexamethasone to inhibit inflammation and prevent oviduct scarring in mice genitally infected with Chlamydia muridarum. The administration of 1 or 2.5 mg/kg of body weight of dexamethasone on days 7 to 21 of infection resulted in reduced accumulation of inflammatory cells in the oviducts compared to that in controls. However, a concomitant increase in bacterial burden was observed, and chronic oviduct disease was not reduced. Adjunctive administration of a prolonged (21-day) or short (3-day) course of dexamethasone in combination with the antibiotic doxycycline also failed to reduce chronic oviduct pathology compared to antibiotic treatment alone. Steroids administered alone or adjunctively with antibiotics failed to prevent oviduct damage in this murine model of C. trachomatis infection.     

Clinical experience of smoking cessation advice in hospital trauma units

Introduction  

Cigarette smoking is increasingly well recognized as an inhibiting factor in fracture healing, and risk factor for non-union. We assessed whether adequate smoking cessation advice and support was given to cigarette smokers undergoing fracture management, based upon the United States Public Health Service ‘Five As’ Smoking Cessation Guidelines—evidence-based guidelines outlining effective strategy to promote smoking cessation, by taking a smoking history, advising the patient to stop smoking, assessing motivation to stop and facilitating cessation via support groups and pharmacological interventions (Ask, Advise, Assess, Assist, Arrange).     

荧光杂交探针技术检测单核苷酸多态性

目的 建立一种基于荧光杂交探针技术快速检测单核苷酸多态性方法。方法 提取线粒体DNA，在LightCycler仪器上进行实时PCR和熔解曲线分析，测序验证。结果 熔解曲线分析获得的150个基因型分析结果与测序结果100％一致。结论 实时PCR和杂交探针技术能快速、有效的检测单核苷酸多态性。     

Secretion of extracellular matrix-degrading proteinases is increased in epithelial ovarian carcinoma

The biochemical events associated with tumor invasion involve localized degradation of the basement membrane by tumor-associated proteinases. In this study, we have characterized the proteinase secretion profiles of 5 ovarian epithelial carcinoma cell lines (DOV 13, OVCA 420, OVCA 429, OVCA 432, OVCA 433) as well as normal ovarian epithelial cells. Immunocapture assays demonstrated that all 5 carcinoma cell lines produce both secreted and surface-associated plasminogen activator. Urinary-type plasminogen activator (u-PA) production was one order of magnitude greater than production of tissue-type plasminogen activator (t-PA). Furthermore, t-PA secretion by normal ovarian epithelial cells was not detectable, whereas u-PA production was 17-to 38-fold lower than in ovarian carcinoma cells. Western-blotting analysis demonstrated that u-PA was secreted as the single chain form (scu-PA) when cells were cultured in serum-free medium. Incubation of plasminogen with ovarian carcinoma cell-conditioned medium resulted in direct activation of the Zymogen to plasmin. Furthermore, following incubation of cells with plasminogen, plasmin was eluted from the cell surface, indicating that ovarian carcinoma cells contain binding sites for plasminogen/plasmin which are accessible to surface-associated plasminogen activators. In addition to plasminogen activators, metalloproteinases were also produced by DOV 13, OVCA 429 and OVCA 433 cells. DOV 13 cells produce a 68-kDa metalloproteinase similar to matrix metalloproteinase 2 (MMP-2) whereas a 92-kDa enzyme similar to MMP-9 is secreted by OVCA 429 and 433. Together, ovarian carcinoma-associated plasminogen activators and metalloproteinases catalyze the hydrolysis of the major basement membrane protein components, type-IV collagen, type-IV gelatin, laminin and fibronectin. The enhanced proteolytic capability of ovarian carcinoma cells relative to normal ovarian epithelium suggests a biochemical mechanism by which invasion and spread of ovarian epithelial carcinoma may be mediated.     

Severe megacystis and bilateral hydronephrosis in a female fetus

The differential diagnosis for antenatal bladder dilation and hydronephrosis is extensive, ranging from posterior urethral valves to neurogenic bladder. We present a case of a female fetus diagnosed antenatally with severe megacystis and bilateral hydroureteronephrosis. The patient was found to have megacystis-microcolon-intestinal hypoperistalsis syndrome, a rare, congenital, and generally fatal disorder in which there is functional obstruction of the bladder and intestine.     

Conjunctival T-cell subpopulations in Sjögren's and non-Sjögren's patients with dry eye

PURPOSE: To examine the conjunctiva of patients with Sj?gren's syndrome keratoconjunctivitis sicca (SS-KCS) and non-Sj?gren's keratoconjunctivitis sicca (NS-KCS) for evidence of immune-based inflammation. METHODS: Conjunctival biopsy specimens were obtained from 15 patients with SS-KCS and 15 with NS-KCS. Immunohistochemistry was performed on frozen sections to characterize and quantify T-cell subtypes (CD3, CD4, and CD8) and markers of immune activation (major histocompatibility complex [MHC] class II: HLA-DR, HLA-DQ) and inflammation (intercellular adhesion molecule [ICAM]-1). The numbers of cells positive for each marker were counted by two masked observers and averaged. RESULTS: Conjunctival biopsy specimens from patients with SS-KCS or NS-KCS revealed lymphocytic infiltration and increased immunoreactivity for the markers of inflammation and immune activation. The extent of cellular immunoreactivity did not differ significantly between SS-KCS and NS-KCS tissue samples. CONCLUSIONS: The authors' findings indicate that patients with SS-KCS or NS-KCS have conjunctival inflammation manifested by inflammatory cell infiltrates and upregulation of expression in markers of immune activation. Clinical symptoms of KCS may be more dependent on T-cell activation and resultant inflammation than previously believed. In addition to tear substitutes, anti-inflammatory therapeutics should be investigated for the treatment of KCS.     

Neuropeptide Y-Y2 receptors mediate anxiety in the amygdala

The behavioral effects of direct injection of the neuropeptide Y (NPY) Y2 receptor agonist C2-NPY into the basolateral nucleus of the amygdala (BLA) was assessed in rats utilizing the social interaction test (SI). C2-NPY decreased SI time in a dose-dependent manner with a significant change observed at a dose of 80 pmol/100 nl. The anxiogenic effects produced by intra-amygdalar C2-NPY injections were reversed with intraperitoneal administration of alprazolam (1 mg/kg), a known anxiolytic. These findings support the hypothesis that Y2 receptors are involved in the regulation of the anxiety response.