Either desipramine or TMB-8 suppresses cyanide-induced norepinephrine efflux from in vivo cardiac sympathetic nerves of cats

To investigate the effect of hypoxia on endogenous norepinephrine (NE) release from cardiac sympathetic nerve ending, we administered sodium cyanide (NaCN) for 30 min into the myocardial interstitial space through a dialysis probe and measured dialysate NE levels. During the NaCN perfusion, a marked and concentration-dependent increase in dialysate NE was observed. This cyanide-induced NE response was suppressed by pretreatment with despiramine (a membraneous NE transport inhibitor). Furthermore, the cyanide-induced NE response was suppressed by pretreatment with TMB-8 (intracellular Ca(2+) antagonist) but unaffected by omega-conotoxin GVIA (NE releasing inhibitor). Our data suggest that two (desipramine or TMB-8 suppressive) mechanisms contributed to the amount of NE efflux induced by cyanide in in vivo cardiac sympathetic nerve.     

The importance of free hydroxyl radicals to hypoxia preconditioning

Hypoxia preconditioning states that a sublethal hypoxia period will afford neuroprotection against a second harmful event. In our experiments, we carried out a procedure for the development of hypoxia preconditioning in adult male Wistar rats using hypoxic exposure (9% O(2); 91% N(2)) for 1 h. The protection against pentylenetetrazol (PTZ)-induced seizures was studied. For this, rats were tested by a single injection of PTZ (55 mg/kg i.p.) on days 1-21 after hypoxia exposure. The hypoxia exposure significantly prevented the development of acute PTZ convulsion at different times after hypoxia. The present study was designed to determine the effect of N-t-butyl-alpha-phenylnitrone (PBN), an electron-trapping agent and free radical scavenger, on hypoxia preconditioning against PTZ seizures 7 days after hypoxia exposure. PBN abolished the protective action of hypoxia exposure. The generation of free hydroxyl radicals in the brains of animals exposed to hypoxia was determined in a second experiment. For this purpose, the rats were i. p. pretreated with 30 mg/kg PBN and NaCl, respectively, 20 min before the start of hypoxia exposure. Forty-five minutes later the rats were i.p. injected with 300 mg/kg sodium salicylate and once again exposed to hypoxia for 15 min. Immediately after that the animals were decapitated and the free hydroxyl radicals and the salicylate content were estimated in the whole brain without cerebellum. Hypoxia preconditioned animals pretreated with NaCl showed a significantly higher extent of free hydroxyl radicals in the brain compared with PBN-injected preconditioned animals and with naive and sham exposed controls. The results pointed out that the generation of free reactive oxygen species under hypoxic conditions in the brain is involved in the development of the hypoxic preconditioning phenomenon.     

缺氧诱导因子HIF-1α、3α在血管瘤不同时期的表达和意义

目的 探讨缺氧在血管瘤不同时期的表达和作用.方法 采用免疫组化SP法测定24例增生期血管瘤和18例消退期血管瘤中缺氧染色阳性率,HIF-1α、HIF-3α、VEGF、Ki-67和细胞凋亡表达情况.结果 24例增生期血管瘤中缺氧染色阳性率为80%(19/24),HIF-1α阳性指数为(23.40±4.73)、HIF-3α为(7.90±2.15)、VEGF为(16.90±3.34)、Ki-67为(57.60±11.33)、细胞凋亡指数为(4.50±1.51);而消退期血管瘤中缺氧染色阳性率为90%(16/18),HIF-1α为(9.50±2.67)、HIF-3α为(19.80±2.43)、VEGF为(2.70±0.32)、Ki-67为(11.20±2.65)、细胞凋亡指数为(11.40±2.67).不同时期血管瘤表达的HIF-1α、HIF-3α、VEGF、Ki-67、细胞凋亡指数均有显著性差别(P＜0.05).结论 缺氧是血管瘤不同时期的普遍现象,但对增殖期血管瘤的作用是通过HIF-1α促进内皮细胞繁殖,而对消退期血管瘤是通过HIF-3α促进其凋亡.     

活血解毒方对缺氧/复氧所致心肌细胞凋亡的影响＊

目的 研究活血解毒方对缺氧/复氧（H/R）所致的心肌细胞凋亡的影响。方法 体外培养H9C2心肌细胞并分成正常对照组（Control组）、缺氧复氧组（H/R组）、H/R + 活血解毒中药组、LY294002组和活血解毒中药 + LY294002组，其中正常对照组给予DMEM培养基培养，缺氧复氧组给予缺氧4 h、复氧6 h处理，缺氧复氧 + 活血解毒中药组、LY294002组和活血解毒中药 + LY294002组分别给予活血解毒中药、LY294002、活血解毒中药配合LY294002预处理24 h，然后均给予缺氧4 h、复氧6 h处理。采用CCK8检测各组心肌细胞的存活率，流式细胞术检测各组细胞凋亡水平，电镜观察各组心肌细胞中线粒体、自噬体的变化，Western Blot检测各组细胞凋亡蛋白半胱氨酸天冬氨酸蛋白酶3（Caspase3）、半胱氨酸天冬氨酸蛋白水解酶3（Cleaved caspase3）、β-连环蛋白（β-Catenin）、p-p65、B淋巴细胞瘤-2（B-cell lymphoma-2，Bcl-2）蛋白的表达。结果 活血解毒方预处理显著增加H/R诱导的H9C2心肌细胞凋亡，降低凋亡相关蛋白Cleaved caspase3、β-Catenin、p-p65表达，增加Bcl-2表达。结论 活血解毒方可通过抑制细胞凋亡，降低缺氧/复氧所致的心肌细胞损伤，其作用机制可能与PI3K信号通路相关。     

Antitumor effect of the angiogenesis inhibitor bevacizumab is dependent on susceptibility of tumors to hypoxia-induced apoptosis

Angiogenesis inhibition has been shown to enhance the therapeutic efficacy of cytotoxic chemotherapy in colorectal cancer. The basis of the contribution of this modality has not been defined fully. To determine the potential role of hypoxia-induced apoptosis, we studied a series of colon cancer cell lines with varying susceptibility to hypoxia. We exposed HT29 and HCT116 colon adenocarcinoma cell lines to sublethal periods of hypoxia three times weekly for 40 exposures, and derived cell lines both more resistant (from HT29) and more sensitive (from HCT116) to hypoxia-induced apoptosis. Both hypoxia-derived cell lines demonstrated more rapid growth than the parental lines when implanted subcutaneously in immunodeficient mice. Treatment of tumor-bearing mice with bevacizumab resulted in depletion of tumor microvasculature, upregulation of Hypoxia-inducible factor-1 alpha (HIF-1alpha), and increased pimonidazole staining, consistent with an anti-angiogenic effect and induction of hypoxia in tumors derived from all cell lines. The proportion of apoptotic cells was increased in all the treated tumors, and was most pronounced in the bevacizumab-treated HCT116-derived cells. The bevacizumab-treated tumors showed growth delay in HT29 and its derivative, and the parental HCT116. In the hypoxia-sensitive HCT116-derived tumors, marked tumor shrinkage and prolonged growth control occurred. Therefore, bevacizumab treatment is an effective inducer of a hypoxic environment, but the resulting cell kill and tumor shrinkage is determined by the susceptibility of the tumor to apoptosis. The induction of apoptosis by hypoxia may contribute to the benefits of such treatment in the clinical setting.     

A long-standing incomprehensible matter of obstetrics: meconium-stained amniotic fluid,a new approach to reason

Objective

We sought to determine whether meconium-stained amniotic fluid is based on chronic hypoxia or not? In case of chronic hypoxia, higher red blood cell (Rbc) count and/or total hemoglobin levels (Hgb) and/or higher fetal hemoglobin (HbF) and/or lower adult hemoglobin (HbA) levels were expected when compared with controls.

Design

Case–control study.

Setting

Obstetric unit of a tertiary ministry of health hospital.

Sample

Fifty singleton pregnancies with meconium-stained amniotic fluid and 50 singleton pregnancies with clear amniotic fluid at all stages of labor.

Methods

Umbilical cord blood samples were collected for determination of total blood parameters and hemoglobin electrophoresis.

Main outcome measures

Red blood cell count, total hemoglobin, fetal and adult hemoglobin contents (HbF and HbA).

Results

Red blood cell count, total hemoglobin, fetal hemoglobin (HbF) and adult hemoglobin (HbA) contents were not different between meconium stained and clear amniotic fluid groups.

Conclusion

These results suggest that meconium passage may not be associated with chronic fetal hypoxia as demonstrated by similar red blood cell count, total hemoglobin values and fetal hemoglobin (HbF) and adult hemoglobin (HbA) contents.

     

复方丹参滴丸对大鼠高原低氧组织病理损害的干预作用

目的探讨复方丹参滴丸(DSP)对高原低氧多器官组织病理改变的影响。方法将平原大鼠运入高原(海拔5000m),随机分为DSP干预组(7只)和对照组(7只),实验20天后全部处死,取出心、肝、脾、肺、肾、脑组织用光电镜观察。结果与对照组比较,DSP干预组大鼠的组织病理改变明显轻微。结论DSP能预防、改善细胞的低氧性水肿、变性、坏死等损伤,是高原自然环境条件下比较特异的低氧性器官组织损伤的保护剂。     

糖皮质激素对鼻息肉缺氧诱导因子-1α及血管内皮生长因子表达的影响

目的 探讨组织缺氧诱导因子-1α(HIF-1α）及血管内皮生长因子（VEGF）在鼻息肉组织中的表达及相关性, 探讨局部应用糖皮质激素类药物对鼻息肉的作用机制。方法 采用免疫组化SP法检测鼻息肉组织在应用丙酸氟替卡松鼻喷剂治疗前、后及下鼻甲HIF-1α及VEGF的表达变化。结果 鼻息肉组织中HIF-1α和VEGF的表达水平明显高于下鼻甲组织（P均＜0.01）;激素治疗后HIF-1α、VEGF表达下降(P＜0.05)。鼻息肉的发病与组织中HIF-1α、VEGF的表达呈明显正相关（r=0.627, P＜0.05）。结论 局部应用糖皮质激素可降低HIF 1α、VEGF的表达,有效治疗鼻息肉。     

Usefulness of measuring the gastric emptying time in a case of brittle diabetes

Gastric emptying time measurement by radionuclide study, although quite informative, is rarely remembered in clinical practice. We presented a patient with brittle diabetes who had multiple emergency admissions due to hypoglycemia under routinely prescribed insulin therapy. She had severe gastroparesis, which was determined by scintigraphic gastric emptying study (gastric half-emptying time = 260 min for a mixed meal). She had not presented to the emergency service for two years because of only a slight change the timing of her insulin administration time (after meal instead of before meal) in the light of gastric-emptying study.     

轻、中度缺氧应激时亮度对比度对脑认知功能的影响

目的 选出轻、中度缺氧条件下最佳亮度对比度值。方法 １４名受试者在地面及１５００ｍ、３０００ｍ、５０００ｍ在模拟高度（吸低氧混合气体）分别进行５种不同亮度对比度（８：１、１０：１、１２：１、１４：１、１６：１）的视觉Ｏｄｄｂａｌｌ测试,记录脑电图（ＥＥＧ）及反应时,ＥＥＧ经叠加平均处理提取出脑事件相关电位（ＥＲＰ）中的Ｐ３潜时。以Ｐ３潜时和ＲＴ为主要指标评定脑认知能力。采用两因素析因分析及统计学处理。结果 在地面及１５００ｍ,五个亮度对比度的视觉Ｏｄｄｂａｌｌ任务的Ｐ３潜时及ＲＴ无明显差别,在３０００ｍ、５０００ｍ,１４：１及１６：１两个对比度的Ｐ３潜时及ＲＴ明显短于其它对比度的Ｐ３潜时和ＲＴ,其中对比度为１４：１及１６：１两上对比度的Ｐ３潜时及ＲＴ最短。结论 在３０００ｍ及５０００ｍ高度中度缺氧条件下,对比度