Extra- and intracellular free iron and the carotid body responses

The hypothesis that chelation of free iron, by decreasing reactive oxygen species (ROS), might mimic hypoxia and stimulate the carotid body was tested. We used the iron chelators, desferrioxamine (DFO, 200-400 microM) initially, and later ciclopirox olamine (CPX, 2.5-5.0 microM), on rat carotid body in vitro and measured chemosensory activity and [Ca2+]i in isolated cultured glomus cell clusters during normoxia and hypoxia. Although acute treatment of DFO might not penetrate the cell, and extracellular DFO would not influence these activities whereas CPX significantly increased chemosensory activities as well as increased [Ca2+]i in normoxia. We concluded that chelation of extracellular free iron did not alter ROS formation and oxygen sensing. Chelation of intracellular free iron and, therefore, a decrease in intracellular ROS appears to influence oxygen sensing in the carotid body.     

Two unusual benign lesions of the neck masquerading as malignancy on fine-needle aspiration cytology

Two cases of unusual benign tumors of the neck are described, both of which were initially misdiagnosed on cytology as carcinomas. Fine-needle aspiration findings in each case demonstrated a pleomorphic population of cells including bizarre multi-nucleated giant cells, the latter raising the false impression of malignancy. However, on review the cytological appearances of the tumors, a pleomorphic lipoma and a carotid body tumor, were characteristic. the correct diagnosis in each case would have been made or suggested if the pathologist had been familiar with the cytologic features characteristic of the lesion and the differential diagnosis of the head and neck tumors. in addition, the point is made that adequate clinical information is essential for the pathologist if all relevant conditions are not to be missed in the differential diagnosis.     

An association of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and common carotid atherosclerosis

Plasma homocysteine (Hcy) concentration has been shown to be influenced by a mutation in the gene coding methylenetetrahydrofolate reductase (MTHFR). Although plasma Hcy is related to atherosclerotic disorders, conflicting results have been reported about the association between MTHFR gene polymorphism and sclerotic lesions of the common carotid arteries. The effect of age–gene interaction on carotid arterial remodeling was investigated in elderly subjects with several risk factors for atherosclerosis. We evaluated sclerotic lesions of the common carotid arteries by ultrasonography in 326 patients (mean age ± standard deviation, 73 ± 12 years) and studied relations among the known risk factors for atherosclerosis, including MTHFR gene polymorphism and its interactions with age and sex. Of the 326 subjects studied, 136 had MTHFR genotype CC, 136 genotype CT, and 54 genotype TT. The three groups did not differ with respect to background factors such as age, history of cigarette smoking, blood pressure, lipids or uric acid, or in the incidence of atherosclerotic diseases. Spearman's rank correlation revealed a significant relationship between gender, age, Brinkman index, systolic blood pressure, triglycerides, HDL-cholesterol (HDL-C), uric acid, and MTHFR gene polymorphism. Multiple regression analysis using intima-media complex thickness (IMT) as a criterion variable and risk factors, including MTHFR gene polymorphism as explanatory variables showed that MTHFR gene polymorphism (P = 0.039) was a significant independent explanatory variable for IMT, along with gender (male) (P < 0.001), age (P < 0.001), systolic blood pressure (SBP) (P = 0.047), total cholesterol (T-C) (P < 0.001), and HDL-C (P < 0.001). Furthermore, a general linear model analysis revealed that interaction between age and MTHFR gene polymorphism was significantly associated with IMT, independently of age, SBP, T-C, and HDL-C in male subjects. However, age–gene interaction was not observed in female subjects. The findings of the present study confirm an association between MTHFR gene polymorphism and common carotid atherosclerosis in the Japanese population and further support the role of risk factor–gene interaction in common carotid atherosclerosis. Received: May 14, 2001 / Accepted: June 8, 2001     

Chemoreceptor responses to substance P, physalaemin and eledoisin: Evidence for neurokinin-1 receptors in the cat carotid body

Substance P (SP) belongs to a group of peptides called tachykinins. Biological effects of SP are mediated by tachykinin receptors that have been classified as neurokinin-1 (NK-1), NK-2 and NK-3 subtypes. The aim of the present study is to elucidate the tachykinin receptor subtype(s) that mediate the excitatory effects of SP in the carotid body. For this purpose, we compared the carotid body responses elicited by SP with that of physalaemin and eledoisin. In other tissues, physalaemin exhibits equi or greater potency at NK-1 receptors and eledoisin exerts its effects more on NK-2 and NK-3 subtypes compared to SP. Experiments were performed on eight cats that were anaesthetized, paralyzed and artificially ventilated with room air. Close carotid body administration of SP and physalaemin produced dose-dependent augmentation of the chemoreceptor afferent activity. Chemoreceptor discharge, however, was unaffected by eledoisin. Compared to that by SP, the magnitude of excitation produced by physalaemin was the same at lower doses but significantly greater with the highest dose (100 nmol). The time course of the response induced by physalaemin, however, was the same as that by SP. The present results demonstrate that in the carotid body physalaemin is also either equi or relatively more potent than SP, whereas eledoisin has no effect on the chemoreceptor discharge. It is suggested that stimulation of the carotid body by SP is mediated by NK-1 but not NK-2 or NK-3 receptors.     

超声彩色脉搏波技术在定量评价2型糖尿病患者颈动脉弹性变化中的应用

目的 探讨超声彩色脉搏波(UFPWV)技术在定量评价2型糖尿病患者颈动脉血管管壁弹性变化中的应用价值。方法 回顾性研究。纳入2018年7月-2019年3月蚌埠医学院第一附属医院收治的97例2型糖尿病患者为观察组,其中男47例、女50例,年龄20~74(46.6±9.3)岁;根据颈动脉内中膜厚度(IMT)将观察组分为颈动脉粥样斑块组(A组)、颈动脉内中膜增厚组(B组)和颈动脉内中膜正常组(C组),依据下肢动脉有无斑块将C组分为下肢动脉斑块组(C1组)、下肢动脉无斑块组(C2组)。选取2017年12月-2018年12月在蚌埠医学院第一附属医院体检中心血糖及颈动脉IMT正常的健康体检者64人为对照组,其中男25人、女39人,年龄20~74(44.3±12.0)岁。运用UFPWV采集脉搏波速度 (PWV),计算颈动脉收缩早期PWV(PWV-BS)及收缩晚期PWV(PWV-ES),分析各项参数组间的差异。结果 观察组中,A组颈动脉PWV-BS、PWV-ES分别为(9.51±1.25)m/s、(10.79±1.64)m/s,B组分别为(8.47±0.91)m/s、(9.81±1.05)m/s,C组分别为(7.97±0.77)m/s、(9.07±0.74)m/s,对照组颈动脉PWV-BS、PWV-ES分别为(6.10±1.00)m/s、(7.40±1.20)m/s,A组、B组、C组及对照组间颈动脉PWV-BS、PWV-ES测量值依次降低,差异均有统计学意义(P值均<0.05)。C组中,C1组颈动脉PWV-BS、PWV-ES分别为(7.83±0.85)m/s、(8.82±0.59)m/s,C2组分别为(8.14±0.64)m/s、(9.34±0.79)m/s, C1组PWV-ES显著高于C2组,差异有统计学意义(t=3.402,P＜0.01),而两组间PWV-BS的差异无统计学意义(P>0.05)。结论 UFPWV技术可定量评价2型糖尿病患者颈动脉弹性变化,并可通过PWV-ES的改变评估颈动脉形态学正常的患者动脉粥样硬化的进展程度,对临床诊疗具有一定意义。     

The effects of blood osmolality changes on cat carotid body chemoreceptors in vivo

The possibility that carotid chemoreceptors respond to changes in plasma osmolality was investigated in the cat, perfusing the carotid artery with blood made hyper- or hypo-osmotic and recording chemoreceptor activity from carotid nerve fibers. Blood made hyperosmotic with sucrose or NaCl reduced the chemoreceptor discharge, while hypoosmotic blood increased chemoreceptor activity. The minimal osmolality variation necessary to obtain a detectable frequency change was 3–8% of the control. Frequency changes of 30% of the control were obtained with a 20% variation in osmolality. The frequency variations produced by the osmotic changes lasted as long as the infusion was maintained (up to 15 min). In some instances a rebound was observed when iso-osmotic saline was perfused again. A transient change in frequency and a clear rebound were obtained when blood made hyperosmotic with glycerol was perfused. These effects probably reflect a rapid change in intracellular osmolality due to the free passage of glycerol across cellular membranes.The modifications in chemoreceptor activity consecutive to osmolality variations are the opposite of those observed in isolated and superfused carotid bodies. As it is known that osmolality values affect the smooth muscle of the blood vessels, we conclude that our results are mainly produced by changes in carotid body blood flow due to a direct effect of hyper- and hypo-osmotic solutions on vascular muscle tone. Chemoreceptor excitation during a decrease in blood osmolality may contribute reflexly to the increased vascular resistance observed during acute osmolality reductions in man.     

Interaction of peripheral and central respiratory drives in cats I. Effects of sodium cyanide as a peripheral chemoreceptor stimulus at different levels of CSF pH

In cats anesthetized with chloralose-urethane, the central respiratory chemoreceptors were exposed to mock CSF of pH 7.02, 7.20, or 7.57. The right carotid body was simultaneously stimulated by intracarotid injections of 40, 80, or 160 μg sodium cyanide in 200 μl Ringer solution. The left carotid nerve and, in some animals, both vagosympathetic truncs were dissected. It could be demonstrated the the increase in ventilation produced by application of NaCN to the peripheral chemoreceptors is significantly larger at high than at low mock CSF pH (i.e. at low than at high central stimulus intensity). In vagotomized cats the responses of V_T and gelai to NaCN similarly depend upon CSF pH; they are somewhat larger, though, than in intact animals. These results are discussed as compared with results reported by different authors. Supported by the Deutsche Forschungsgemeinschaft (Be 477)     

Effects of carotid sinus nerve transection on changes in neuropeptide Y and indolamines induced by long-term hypoxia in rats

 Long-term hypoxia induces changes in neuropeptide-Y-like immunoreactivity (NPY-LI) and/or in the content of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) at the central level. To determine whether these alterations depend on the integrity of carotid body (CB) chemoreceptors, intact rats or those whose carotid sinus nerve was transected (CSNT) were exposed to hypoxia (10% O₂) or to normoxia for 14 days. Thereafter, NPY-LI, 5-HT and 5-HIAA levels in discrete brain regions were determined. The increase in NPY-LI in the ventrolateral medulla oblongata (VLM) of intact hypoxic rats was mostly abolished after CSNT and therefore is mainly mediated by CB chemoreceptors. In contrast, other hypoxia-induced changes were similar or even enhanced in CSNT as compared to intact rats and therefore do not depend on the integrity of CB chemoreceptors. This was the case for the increase of NPY-LI in the striatum and the caudal dorsomedian medulla oblongata (DMM), as well as for all the changes in 5-HT and 5-HIAA in the DMM, the VLM, the raphe nuclei, the striatum and the frontal cortex. We propose that long-term hypoxia alters brain NPY-LI and indolamine content through the stimulation of CB chemoreceptors or ancillary chemoreceptors, as well as through local biochemical or morphological mechanisms. Received: 5 May 1998 / Received after revision: 27 July 1998 / Accepted: 3 September 1998     

西安市2型糖尿病患者颈动脉狭窄发生情况及其影响因素分析

目的 调查2型糖尿病（T2DM）患者颈动脉狭窄（CAS）的发生率,并探讨影响其发生CAS的相关影响因素。方法 以2018年1月至2020年12月于西安市某医院内分泌门诊首次就诊的T2DM患者为研究对象进行资料收集、体格检查、血生化指标检测及颈动脉超声检查,对T2DM患者CAS检出情况进行描述性分析,并对CAS检出影响因素进行单、多因素分析。结果 2 679例T2DM患者中检出CAS 328例,检出率12.24%。多因素Logistic回归分析表明,年龄越大（OR=1.039）、糖尿病病程越长（OR=1.115）、血糖控制不达标（OR=1.387）、血脂异常（OR=1.970）和高血压（OR=3.725）是T2DM患者合并CAS的危险因素。结论 T2DM患者合并CAS情况突出,应重视对糖尿病病程较长和血糖控制不佳的T2DM患者进行颈动脉超声监测,针对T2DM患者合并CAS的危险因素,应尽早进行控制及预防,避免心脑血管不良事件的发生。     

脑梗塞患者颈动脉粥样硬化斑块的超声研究

目的探讨脑梗塞患者颈动脉粥样硬化病变程度和特征,评价彩色多普勒超声对该粥样斑块的诊断价值.方法应用HP5500超声仪,对35例脑梗塞患者和46例正常人进行颈动脉检查.结果脑梗塞组颈动脉粥样硬化斑块检出率、斑块记分均显著高于对照组[分别为85.7%和21.7%,P＜0.01;(6.745±3.214)mm和(3.408±3.613)mm,P＜0.001],且脑梗塞组软斑比例为55.8%,显著大于对照组33.3%(P＜0.01),脑梗塞组斑块表面不规则即Ⅱ、Ⅲ度的比例亦显著大于对照组(41.9%/11.1%,11.6%/0%,P＜0.05).结论脑梗塞的发生与颈动脉粥样硬化病变密切相关;软斑块是发生脑梗塞的主要危险;超声检查对颈动脉粥样硬化具有诊断价值,可为脑梗塞的预防与治疗提供参考资料.