Exogenous advanced glycosylation end products induce diabetes-like vascular dysfunction in normal rats: a factor in diabetic retinopathy

BACKGROUND. Diabetic retinopathy has been shown to be directly associated with the degree and duration of hyperglycemia, and advanced glycosylation end products (AGEs) have been implicated in this pathological process. The purpose of the experiments reported here was to study the effect of AGE deposition on retinal vascular damage which leads to diabetic retinopathy. METHODS. Intravenous injection of exogenous AGEs was used to treat wild-type non-diabetic Sprague-Dawley rats. One of the two retinal slides from each animal was treated using immunohistochemical staining to label retinal vascular AGE deposition, the other H&E staining for counting of capillary pericytes. The results were compared with the findings in untreated wild-type and diabetic controls and in rats treated with unmodified rat serum albumin (RSA). RESULTS. After 2 weeks of continuous treatment, AGEs were identified in the retinal vascular tissue of the AGE-RSA-injected group. The average number of retinal capillary pericytes per 10x100 microscope power field was 4.313+/-0.34 (mean +/- SD) in the AGE-RSA-injected group, compared with 5.798+/-0.481 in the control group ( P<0.01). CONCLUSION. These experiments demonstrate that AGEs, independent of other metabolic factors, can induce vascular change resembling that of diabetic retinopathy.     

川芎嗪对P2X3受体介导的大鼠伤害性兴奋传入的作用

通过动物痛行为反应(缩足反射)确定局部和鞘内应用川芎嗪(TMP)对ATP等P2X受体激动剂所致大鼠足底急性伤害性行为反应的影响。P2X3受体拮抗剂TNP-ATP(0．3μmol／L)明显抑制P2X受体激动剂ATP(1μmol／L)或α，β-meATP(0．6μmol／L)引起的大鼠足底急性伤害性反应。大鼠足底局部应用TMP(0．1-10mmol／L)剂量依赖性地对ATP(1μmol／L)或α，β-meATP(0．6μmol／L)引起的伤害性反应具有抑制作用。鞘内应用TMP(50mmol／L)对ATP(1μmol／L)或α，β-meATP(0．6μmol／L)引起的伤害性反应具有抑制作用。结果表明，TMP可通过阻断P2X3受体介导的伤害性兴奋传入抑制P2X受体激动剂引起的大鼠足底急性伤害性反应。     

Insulin reduces the BOLD response but is without effect on the VEP during presentation of a visual task in humans.

Functional magnetic resonance imaging (fMRI) based on blood oxygen level-dependent (BOLD) contrast has become an invaluable tool in the assessment of in vivo neuronal activation. Quantification of the BOLD response is determined by the hemodynamic and metabolic changes that occur in response to brain stimulation. However, these changes may vary by changes in insulin, a hormone known to be vasoactive in some tissues. To determine if insulin has an effect on fMRI, we measured the BOLD response to a visual stimulus in five normal volunteers in which insulin was first suppressed and then brought to a high physiological concentration. In addition, we also examined the effect of insulin on activation of the visual cortex as measured by the visual-evoked potential (VEP). We found that the BOLD response measured in the presence of insulin (serum insulin=236+/-29 pmol/L) was significantly lower (P<0.001) than that measured in its absence (serum insulin=8+/-2 pmol/L). Insulin was without effect on P100 amplitude or latency acquired in the presence or absence of insulin in 28 subjects using the same stimulus as that used for the fMRI experiments. Our observations suggest that insulin may have effects on cerebral blood flow and/or metabolism that affect the BOLD signal that are independent of its effects on neuronal activation identified by event related potentials (ERP). These findings highlight the complexity that must be considered when interpreting differences in fMRI responses between groups of subjects that differ in insulin concentration and/or insulin sensitivity.     

Long-term application of diethylstilbestrol upregulates expressions of μ- and m-calpains in pituitary intermediate lobe of female Wistar rats

BACKGROUND: During formation of prolactin neoplasia, how cells and its structure in adenohypophysis affect prolactin cells should be further studied. Intermediate lobe can be regarded as a driving region to release prolactin (PRL) and may promote formation of prolactin neoplasia in pituitary anterior lobe. OBJECTIVE: To observe the effect of diethylstilbestrol (DES) on the expressions of μ and m-calpains in pituitary intermediate lobe of female Wistar rats. DESIGN: Observational contrast animal study. SETTING: Beijing Neurosurgical Institute. MATERIALS: A total of 21 female Wistar rats, 3 weeks old weighing 70–80 g were housed with free access to tap water and standard pellet food. They were kept in a CL-grade condition, at (24±1)℃ and a humidity of (55±5)%, and with a 12 hours day-night cycle. Caprine anti-μ- and m-calpains antibodies were provided by Santa Cruz Biotechnology, CA, USA; rabbit-anti-PRL antibodies by Dako, Denmark; rabbit-anti-ACTH antibody by Boster Company, Wuhan. METHODS: The experiment was carried out in Pathophysiological Department and Animal Laboratory, Beijing Neurosurgical Institute from August 2006 to January 2007. ① Rats were randomly divided into groups with 7 in each group, including vehicle control group, in which rats were injected intraperitoneally with sun-flower seed oil (1 mL/kg, twice a week) for 16 weeks; DES group, where animals were administered with DES (5 mg/kg, twice a week) for 16 weeks; DES + vehicle control group, in which DES was administered for 12 weeks at the same dose with those in DES group, and then was discontinued and replaced by sun-flower seed oil (1 mL/kg, twice a week) for the following 4 weeks. ② At 16 weeks later, pituitary tissue was dealt with HE staining and PRL immunohistochemical examination to observe evoke of tumor; meanwhile, immunohistochemical examination was used to observe expression of PRL of pituitary anterior lobe, expressions of μ- and m-calpains of pituitary intermediate lobe and distribution of adrenocorticotropin. MAIN OUTCOME MEASURES: ① Expression of PRL of pituitary anterior lobe, expressions of μ- and m-calpains of pituitary intermediate lobe and distribution of adrenocorticotropin. ② Morphological observation of pituitary tissue. RESULTS: All 21 rats were involved in the final analysis. ① Results of immunohistochemical examination: Morphological changes of neoplasia in DES group were strongly positive to PRL, and this suggested that formation of prolactin adenoma was observed in pituitary tissue. As compared with vehicle control group, expression of adrenoeorticotropic hormone (ACTH) was increased in both DES group and DES + vehicle control group. In addition, expressions of μ- and m-calpains in pituitary intermediate lobe were higher in DES group than that in vehicle control group. Otherwise, expressions of m-calpains in pituitary intermediate lobe was decreased in DES + vehicle control group, but expression of μ-calpains was still increased. ② Morphological observation of pituitary tissue: Gland tubes were orderly arranged in rats in vehicle control group. Anterior pituitary gland in rats of DES group demonstrated an apparent disappearance of gland tubes and a relatively large-scaled vasculature formation, namely the vascular lake lined by tightly arranged endothelial cells. Local integrated tumor cell arrangements were also detected. In addition, the border between the IL and the anterior lobe was locally blurred. The definite tumor-like changes in pituitary tissues were confirmed in 6 of 7 female Wistar rats in DES group, and one spontaneous occurrence of tumor formation was found in vehicle control group. In DES + vehicle control group, DES withdrawal led to the subtile emergence of gland tube cavity, although tumor-like cells still existed in 4 of 7 rats, suggesting occurrence of the tumor regression due to the withdrawal of DES. CONCLUSION: A long-term application of DES can enhance the expressions of ubiquitours neutral cysteine protease in pituitary intermediate lobe and this suggests that both of them play a key role in release of hormone and formation of prolactin neoplasia through directly promoting PRL expression and release of neighboring pituitary intermediate lobe.     

Maplets for correspondence-based object recognition.

We present a correspondence-based system for visual object recognition with invariance to position, orientation, scale and deformation. The system is intermediate between high- and low-dimensional representations of correspondences. The essence of the approach is based on higher-order links, called here maplets, which are specific to narrow ranges of mapping parameters (position, scale and orientation), which interact cooperatively with each other, and which are assumed to be formed by learning. While being based on dynamic links, the system overcomes previous problems with that formulation in terms of speed of convergence and range of allowed variation. We perform face recognition experiments, comparing ours to other published systems. We see our work as a step towards a reformulation of neural dynamics that includes rapid network self-organization as essential aspect of brain state organization.     

微波快速过氧化物酶染色法与灌注法用于微循环形态学研究之比较

以健康Ｗｉｓｔａｒ大白鼠为材料，对微波快速内源性过氧化物酶染色与灌注法显示微血管的方法进行了对比研究。结果，过氧化物酶组织化学法具有不用灌注，操作简单，所用时间短，对血管无扩张、破裂等人为改变的特点，保持了微血管真实的自然形态和管径大小，可以定量或半定量地判定组织器官活体时的血液循环状况。可以用于人及动物的大脑、脊髓、皮肤、耳及食管等组织内微血管形态学研究和定量分析。并对过氧化物酶显示微血管的原理和微波辐射促进染色的原理及特点进行了分析、讨论。     

Serum creatine kinase B subunit in patients with renal cell carcinoma.

We determined the serum levels of the creatine kinase B subunit (CK-B) by an enzyme immunoassay method in patients with renal cell carcinoma (RCC) and benign renal diseases. Eighteen of 76 patients with RCC (24%) had elevated serum CK-B levels. The positive rates were 29% in stage I, 13% in stage II, 15% in stage III, and 27% in stage IV. In all 9 patients whose serum CK-B levels were serially measured and had been elevated before operation, the CK-B levels were reduced to the normal range after nephrectomy. These findings indicate that serum CK-B is a useful biomarker for monitoring the clinical course for a limited number of RCC patients, but is not a marker for diagnosis and staging. Concentrations of CK-B in RCC tissues were significantly lower than those of normal kidney. A high rate of cell turnover in tumor tissues might entail the higher level of serum CK-B in patients with RCC.     

格林—巴利综合征患者血清和脑脊液中的抗硫脂抗体

探讨抗硫脂抗体与格林－巴利综合征（ＧＢＳ）的关系。方法采用固相酶联免疫吸附法对急性期ＧＢＳ患者血清和脑脊液（ＣＳＦ）中抗硫脂ＩｇＧ和ＩｇＭ抗体进行检测。结果ＧＢＳ患者血清和ＣＳＦ中抗硫脂ＩｇＧ及ＩｇＭ抗体的阳性率均明显高于正常对照组；血清中抗硫脂ＩｇＭ抗体滴度与标本收集时患者发病天数呈负相关（Ｐ＜０．０５），而血清中抗硫脂ＩｇＧ抗体滴度与临床分级（Ｐ＜０．０１）、ＣＳＦ中抗硫脂ＩｇＧ抗体滴度（Ｐ＜０．０１）呈正相关；血清中抗硫脂ＩｇＧ或ＩｇＭ阳性的ＧＢＳ患者，体检时有不同程度的感觉障碍患者为５６％，而血清中抗硫脂抗体阴性患者仅为１６％，两者之间差异有显著意义（Ｐ＜０．０５）。结论抗硫脂抗体可能在ＧＢＳ的病理过程中起重要作用