Brain protection at the blood-cerebrospinal fluid interface involves a glutathione-dependent metabolic barrier mechanism.

The choroid plexuses (CPs) form a protective interface between the blood and the ventricular cerebrospinal fluid (CSF). To probe into the pathways by which CPs provide brain protection, we sought to evaluate the efficiency of glutathione conjugation in this barrier as a mechanism to prevent the entry of blood-borne electrophilic, potentially toxic compounds into the CSF, and we investigated the fate of the resulting metabolites. Rat CPs, as well as human CPs from both fetal and adult brains, displayed high glutathione-S-transferase activities. Using an in vitro model of the blood-CSF barrier consisting of choroidal epithelial cells cultured in a two-chambered device, we showed that glutathione conjugation can efficiently prevent the entry of 1-chloro-2,4-dinitrobenzene (CDNB) into the CSF, a model for electrophilic compounds. The duration of this enzymatic protection was set by the concentration of CDNB to which the epithelium was exposed, and this barrier effect was impaired only on severe epithelial intracellular glutathione and cysteine depletion. The conjugate was excreted from the choroidal cells in a polarized manner, mostly at the blood-facing membrane, via a high-capacity transport process, which is not a rate-limiting step in this detoxification pathway, and which may involve transporters of the ATP-binding cassette c(Abcc) and/or solute carrier 21 (Slc21) families. Supplying the choroidal epithelium at the blood-facing membrane with a therapeutically relevant concentration of N-acetylcysteine sustained this neuroprotective effect. Thus, glutathione conjugation at the CP epithelium coupled with the basolateral efflux of the resulting metabolites form an efficient blood-CSF enzymatic barrier, which can be enhanced by pharmacologically increasing glutathione synthesis within the epithelial cells.     

125I粒子组织间种植对人胃癌裸鼠移植瘤的杀伤作用

目的 观察不同剂量^125I粒子对人胃癌裸鼠移植瘤的杀伤作用及组织损伤。方法 建立人胃癌BGC-823细胞裸鼠皮下移植瘤模型，随机分为对照组和实验组，将不同剂量（100、120、140Gy）地^125I粒子植于实验组。30、60d：比较移植瘤抑瘤率，病理组织学、局部皮肤反应、裸鼠体重及白细胞计数。结果30d，100、120、140Gy组抑瘤率分别为51．93％、79．18％、90．22％，病理组织学反应程度多为RCRG2（45．83％），各实验组组间除120Gy与140Gy（P〉O．05）组外，及分别与对照组比较，差异有统计学意义（P〈0．05）；局部皮肤反应各实验组与对照组比较，差异有统计学意义（P〈0．05），各实验组组间差异无统计学意义（P〉0．05）。60d，各组抑瘤率分别为97．97％、100％、96．69％，病理组织学反应程度以RCRG1居多（62．5％），与对照组比较，差异均有统计学意义（P〈0．05），各实验组组间差异无统计学意义（P〉0．05）；局部皮肤反应随剂量增高而加重，各实验组组间及其分别与对照组比较，差异有统计学意义（P〈0．05）。结论 不同剂量的^125I粒子在不同时间对人胃癌裸鼠皮下移植瘤有显著杀伤作用，但120Gy和140Gy组随剂量累积，损伤明显增加。提示100Gy可能是治疗人胃癌裸鼠皮下移植瘤的有效剂量。     

大学生生涯规划及其对护理教育的意义

对大学生生涯规划及国内外研究状况进行综述，指出生涯规划对护理教育的意义，提出在高等护理教育中加强大学生的生涯规划将是我国护理教育的主要发展方向之一。     

Design-based stereological estimation of hepatocyte number, by combining the smooth optical fractionator and immunocytochemistry with anti-carcinoembryonic antigen polyclonal antibodies.

BACKGROUND/AIMS: Hepatocytes (HEP) have been the major target for structural quantification in the liver, but an estimation of their total number (N), their percentage in relation to the global number of liver cells and the evaluation of the percentage of binucleated hepatocytes (BnHEPs) have never been performed with modern design-based stereological techniques. The establishment of sound technical guidelines and baseline quantitative data in non-pathological conditions are relevant to properly evaluate HEP hyperplasia and BnHEP responses. METHODS: In this study, we combined immunocytochemistry with sound design-based stereology for estimating the N of HEP and the N of non-hepatocytic cells (NHCs). For obtaining systematic uniform random sections (30 microm thick), a smooth fractionator sampling scheme was applied to the liver of five male Wistar rats (3 month old). Those sections were immunostained with polyclonal antibodies against carcinoembryonic antigen. Because biliary canaliculi were then marked, an unequivocal counting of mononucleated hepatocytes (MnHEP) and BnHEP was allowed. RESULTS: The N of HEP was estimated to be 1.93 x 10(9), with a coefficient of error (CE) of 0.02, corresponding to 129 x 10(6) HEP/g of liver. BnHEP represented 26% of total HEP number. The N of NHC was estimated as 1.31 x 10(9) (CE=0.02). CONCLUSION: The strategy here presented provides a reliable method for accessing the N of HEP (distinguishing MnHEP from BnHEP) in situations in which these parameters are relevant, namely for evaluating the magnitude of an hyperplastic liver response from its very early onset.     

Selecting antibodies to detect HER2 overexpression by immunohistochemistry in invasive mammary carcinomas.

There is an increasing clinical demand for HER2 analysis in breast cancer, especially since the release of trastuzumab. The authors assessed the ability of immunohistochemistry to detect HER2 overexpression in invasive mammary carcinomas (IMC) using five antibodies. Paraffin-embedded samples of 86 IMCs (T2N0) were used to compare the immunohistochemical overexpression of HER2 using two polyclonal antibodies (HercepTest [DAKO] and A0485 [DAKO]) and three monoclonal antibodies (CB11 from two different laboratories, Biogenex and Novocastra, and 4D5 [Genentech]). All immunostainings were scored according to the FDA-approved HercepTest recommendations. The HercepTest-positive cases were compared with gene amplification by FISH (Oncor Inform, Ventana). The HercepTest was positive in 31 of the 86 cases (36.1%). The DAKO antibody A0485 was positive in 25 of the 66 (37.8%). Monoclonal antibody 4D5 was positive in only 15 of the 86 cases (17.4%). There was almost total agreement in results between the two CB11 antibodies: 25 of the 86 positive cases (29.1%). All cases positive for CB11 or 4D5 were HercepTest positive. Most of the HercepTest 2+ cases were negative when using either monoclonal antibody. FISH was positive in 19 of the 20 HercepTest 3+ cases and negative in 5 HercepTest 2+ cases. Three CB11-2+ cases showed no amplification by FISH. In three FISH-positive cases the immunohistochemistry showed no overexpression by all antibodies used. These findings suggest that immunohistochemistry may be used reliably as a primary methodology for evaluating HER2; however, the use of polyclonal antibodies may not be adequate to assess HER2 overexpression. CB11, regardless of the manufacturer (Biogenex or Novocastra), showed better concordance with FISH (kappa=0.83) than did the polyclonal antibodies.     

Muscle protein metabolism during hemodialysis.

Despite improvement in many aspects of the care of maintenance hemodialysis (HD) patients, protein-calorie malnutrition, which is characterized by an insidious loss of somatic protein, is common and is a major risk factor for increased morbidity and mortality. We present here an overview of the current knowledge on protein metabolism in uremic patients with the expectation of providing insights into the mechanisms involved in HD-associated catabolism and outlining the rationale underlying intradialytic nutrition. We concentrate on the discussion of muscle protein metabolism because muscle is the predominant site of protein storage, and its integrity is mandatory for the maintenance of a good quality of life.     

Course of depressive symptoms and medication adherence after acute coronary syndromes: an electronic medication monitoring study.

OBJECTIVES: We tested whether improvements in depressive symptoms precede improved adherence to aspirin in patients with acute coronary syndromes (ACS). BACKGROUND: Depression is associated with medication nonadherence in patients with ACS, but it is unclear whether changes in depression impact on adherence. METHODS: Electronic medication monitoring was used to measure adherence to aspirin during a 3-month period in a consecutive cohort of 172 patients (25 to 85 years) recruited within 1 week of hospitalization for ACS. Depressive symptom severity was assessed using the Beck Depression Inventory (BDI) during hospitalization and at 1 and 3 months after hospitalization. Adherence was defined as the percentage of days aspirin was taken as prescribed. RESULTS: Depression severity in hospital was associated with nonadherence in a gradient fashion: 15% of non-depressed patients (BDI score 0 to 4), 29% of mildly depressed patients (BDI score 10 to 16), and 37% of patients with moderately-to-severely depressive symptoms (BDI score >16) took aspirin less than 80% of the time (p = 0.03). A cross-lagged path analytic model revealed that improvements in depressive symptoms in the first month after the ACS were associated with improvements in adherence rates in the subsequent 2 months (standardized direct effect -0.32, p = 0.016). CONCLUSIONS: Diagnosis and treatment of depressive symptoms may improve medication adherence in patients after ACS.