The N-methyl-D-aspartate antagonist, MK-801, fails to protect against neuronal damage caused by transient, severe forebrain ischemia in adult rats

The neuroprotective effects of dizocilipine maleate (MK-801), a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor/channel, were tested in the 4-vessel occlusion rat model of forebrain ischemia. Adult Wistar rats, treated intraperitoneally with MK-801 or saline using several different treatment paradigms were subjected to 5 (n = 208) or 15 (n = 62) min of severe, transient forebrain ischemia. In saline-treated animals, 15 min of ischemia (n = 13) produced extensive and consistent loss of pyramidal neurons in the CA1 zone of hippocampus. The degree and distribution of cell loss were not reduced by single dose preischemic administration of MK-801 at 1 (n = 7), 2.5 (n = 4), or 5 mg/kg (n = 8). In other animals subjected to 15 min of forebrain ischemia, multiple doses of MK-801 (5, 2.5, and 2.5 mg/kg) given immediately and at approximately 8 and 20 hr after cerebral reperfusion (n = 5) did not alter CA1 injury compared to saline-treated controls (n = 5). Five minutes of forebrain ischemia in saline-treated animals, (n = 82) resulted in significantly fewer (p less than 0.001) dead CA1 pyramidal cells and a greater variance compared to animals subjected to 15 min of ischemia. Power analysis of the preliminary saline-treated animals subjected to 5 min of ischemia (n = 22) indicated that 60 animals per group were necessary to detect a 15% difference between MK-801 and vehicle-treated groups. Multidose treatment with MK-801 (1 mg/kg) given 1 hr prior to 5 min of ischemia (n = 60) and again at approximately 8 and 16 hr after recirculation failed to attenuate hippocampal injury.(ABSTRACT TRUNCATED AT 250 WORDS)     

Therapy of human cervical carcinoma with monoclonal antibody-Pseudomonas exotoxin conjugates.

Pseudomonas exotoxin A (PE) linked to the F(ab')2 fragment of 1H10, a murine monoclonal antibody recognizing a carbohydrate epitope of a glycoconjugate expressed on the surface of human cervical carcinoma tumor cells, was evaluated for in vitro and in vivo activity. PE can kill cells by ADP-ribosylating elongation factor 2 thus inhibiting protein synthesis. Disulfide- as well as thioether-linked immunotoxins (1H10-PE) killed cervical carcinoma cells in vitro and were 20-160 times more inhibitory to target than to control cells. Cell killing was antibody mediated as demonstrated by the reduction of 1H10-PE growth inhibition to target CaSki cells by free 1H10 F(ab')2. In addition, a control antibody immunotoxin was nontoxic to CaSki cells. Thioether-linked 1H10-PE administered either i.v. or i.p. suppressed the growth of established solid s.c. cervical carcinoma tumors xenografted in nude mice for over 30 days. Treatment with antibody alone or a control immunotoxin had no significant effect on tumor growth. Administration of immunotoxin i.p. was associated with less toxicity than administration i.v., but i.v. injections were more effective at suppressing the growth of established solid tumors.     

Ischemic rat brain extracts induce human marrow stromal cell growth factor production

Intravenous administration of human bone marrow stromal cells (hMSCs) after middle cerebral artery occlusion (MCAo) in rats provides functional benefit. We tested the hypothesis that these functional benefits are derived in part from hMSC production of growth and trophic factors. Quantitative sandwich enzyme‐linked immunosorbent assay (ELISA) of hMSCs cultured with normal and MCAo brain extracts were performed. hMSCs cultured in supernatant derived from ischemic brain extracts increased production of brain‐derived neurotrophic factor (BDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). These neurotrophins and angiogenic growth factors increased in a post‐ischemia time‐dependent manner. The hMSC capacity to increase expression of growth and trophic factors may be the key to the benefit provided by transplanted hMSCs in the ischemic brain.     

Protein synthesis and degradation in skeletal muscle of chronically uremic rats

We used the perfused hemicorpus preparation to measure individual rates of protein synthesis and degradation. Using fed animals, perfused either with or without insulin, muscle protein synthesis and hemicorpus protein degradation rates were similar, but myofibrillar protein degradation was clearly increased in the uremic preparations. When the animals were fasted, differences in the rates of skeletal muscle protein turnover were apparent. Uremic rats lost more wt at both 24 and 48 hr of fasting when compared to either ad libitum fed or pair-fed controls who started fasting at body wts equivalent to our uremic rats. The accelerated wt loss was accompanied by lower rates of protein synthesis, higher degradation rates, and greater net protein catabolism in our uremic rats. Alterations in body lipid content were present in uremia and correlated with the rate of protein degradation in both control and uremic rats. These data demonstrated that even in the fed state, uremia is associated with subtle alterations in skeletal muscle protein turnover. When stressed, these alterations become more pronounced. Insufficient stores of body lipids, either due to inadequate nutrition or altered metabolism, may contribute to the alterations in muscle protein turnover seen in chronic renal insufficiency.     

An etiological and clinicopathological study of early syphilis in oropharynx]

OBJECTIVE: To investigate the characteristics of the early stage treponema pallidum infected tissue in ear, nose, oropharynx and larynx and to raise relevance ratio of syphilis in nose and oropharynx and enhance doctor's self-protection awareness. METHODS: The histopathologic characteristics were studied by using HE staining, Warthin-Starry (W-S) staining was adopted to examine the treponema pallidum(TP) in lesion issue and its exudates smear for 12 cases biopsy tissues of suspicious syphilis. The diagnosis was confirmed by venereal disease research laboratory (VDRL), rapid plasma reagin circle test(RPR), treponema pallidum hemagglutination test(TPHA) and fluorescent treponemal antibody-absorption test (FTA-ABS). Treat with curing syphilis methods which published by nation. RESULTS: In the 12 cases mucous membrane specimen, the squamous epithelium proliferated, neutrophilic granulocyte infiltrated, within inherent membrane generous plasmacyte and lymphocyte infiltrated. W-S staining: plenty of treponema pallidum were found inside mucous membrane epithelium and exudate smear. Serology examination: 11 cases VDRL(++++), 7 cases RPR (+), 11 cases TPHA(+), 1 case FTA-ABS(+). After systemic treatment, 11 cases are clinically recovered. All patients serology become negative. CONCLUSION: W-S staining method can directly demonstrate histopathologic characteristics in early syphilis, in intrinsic membrane numerous plasmacyte infiltration. Combining with specific syphilis serology examination could increase diagnosis rate of syphilis in nose and oropharynx.     

后SARS时期对公共卫生与健康的再思考

在人们印象中“公共卫生”是一个很模糊的领域，它比较形象的载体可能就是爱国卫生运动或预防接种。美国1932年提出的公共卫生的定义，对现在依然有指导意义：公共卫生就是预防疾病，延长寿命，通过有组织的社会共同努力来改变环境卫生，从而促进身体的健康，提高工作效率，控制社区传染病的流行，教育个人形成良好的卫生习惯，组织医护人员对疾病进行早期的诊断和预防性治疗。简而言之，“公共卫生”就是关注公众健康的科学。公共卫生学不能脱离临床医学，后是对某种疾病的个体的治疗，而前则着眼对某种疾病做群体防护。     

穿琥宁粉针雾化吸入治疗小儿呼吸道病毒感染疗效观察

小儿呼吸道感染是小儿科最常见的疾病，以咽炎、扁桃体炎、气管炎和肺炎多见。病原体以病毒感染为主。未经治疗有诱发心肌炎、脑炎的可能，应积极进行有效治疗。我们自2004年6月至12月应用注射用穿琥宁冻干粉剂雾化吸入治疗小儿呼吸道病毒感染58例，取得满意效果，现总结报告如下：     

西药对中医脉象的影响

笔者毕业后十余年中,临床上遇到心脑血管病人大部分正在应用西药治疗,中医讲究辨证论治,西药是否影响中医的辨证,临床上脉象是否随着西药运用而改变呢?中医脉象学是中医诊病、治病重要手段,望闻问切中“切诊”是主要组成部分。脉象变化是辨证论治重要依据,求证离不开脉象,组成脉象的主要因素及原因有:①脉位:脉动显现部位的浅深,脉位表浅为浮脉,深沉为沉弦;②至数:脉搏的频率,以一个呼吸周期为单位,一息脉来四~五至为平脉,一息六至为数脉,一息三至为迟脉;③脉长:脉动应指的轴向范围长短,越超三部脉象称为长脉,应指不及三部,但见关部或寸部者…     

In vivo PET imaging of cardiac presynaptic sympathoneuronal mechanisms in the rat.

The sympathetic nervous system of the heart plays a key role in the pathophysiology of various cardiac diseases. Small-animal models are valuable for obtaining further insight into mechanisms of cardiac disease and therapy. To determine the translational potential of cardiac neuronal imaging from rodents to humans, we characterized the rat sympathetic nervous system using 3 radiotracers that reflect different subcellular mechanisms: (11)C-meta-hydroxyephedrine (HED), a tracer of neuronal transport showing stable uptake and no washout in healthy humans; (11)C-phenylephrine (PHEN), a tracer of vesicular leakage and intraneuronal metabolic degradation with initial uptake and subsequent washout in humans; and (11)C-epinephrine (EPI), a tracer of vesicular storage with stable uptake and no washout in humans. METHODS: We used a small-animal PET system to study healthy male Wistar rats at baseline, after desipramine (DMI) pretreatment (DMI block), and with DMI injection 15 min after tracer delivery (DMI chase). The rats were kept under general isoflurane anesthesia while dynamic emission scans of the heart were recorded for 60 min after radiotracer injection. A myocardial retention index was determined by normalizing uptake at 40 min to the integral under the arterial input curve. Washout rates were determined by monoexponential fitting of myocardial time-activity curves. RESULTS: At baseline, HED showed high myocardial uptake and sustained retention, EPI showed moderate uptake and significant biphasic washout, and PHEN showed moderate uptake and monoexponential washout. The average (+/- SD) left ventricular retention index for HED, PHEN, and EPI was 7.38% +/- 0.82%/min, 3.43% +/- 0.45%/min, and 4.24% +/- 0.59%/min, respectively; the washout rate for HED, PHEN, and EPI was 0.13% +/- 0.23%/min, 1.13% +/- 0.35%/min, and 0.50% +/- 0.24%/min, respectively. The DMI chase resulted in increased washout only for HED. DMI block decreased myocardial uptake of all tracers by less than 90%. CONCLUSION: Kinetic profiles of HED in the rat myocardium were similar to those of HED in humans, suggesting comparable neuronal transport density. Unlike in humans, however, significant washout of EPI and faster washout of PHEN were encountered, consistent with high intraneuronal metabolic activity, high catecholamine turnover, and reduced vesicular storage. This evidence of increased neuronal activity in rodents has implications for translational studies of cardiac neuronal biology in humans.