乳腺癌和瘦素相关性研究进展

肥胖是乳腺癌的一个危险因素，瘦素作为肥胖基因的产物，与肥胖密切相关。在乳腺癌患者中，血清中瘦素水平显著升高；乳腺癌患者的脂肪组织和乳腺上皮细胞中也发现有LpmRNA和瘦素受体表达。研究还证实：瘦素可以通过旁分泌和内分泌作用于乳腺上皮细胞，促使乳腺癌细胞的生长。结果表明，瘦素作为肥胖因子可能在肥胖致乳腺癌的过程中起重要作用。提供了一个为什么肥胖症与乳腺癌相关的解释。     

乳腺癌和瘦素相关性研究进展

肥胖是乳腺癌的一个危险因素,瘦素作为肥胖基因的产物,与肥胖密切相关。在乳腺癌患者中,血清中瘦素水平显著升高;乳腺癌患者的脂肪组织和乳腺上皮细胞中也发现有Lpm RNA和瘦素受体表达。研究还证实:瘦素可以通过旁分泌和内分泌作用于乳腺上皮细胞,促使乳腺癌细胞的生长。结果表明,瘦素作为肥胖因子可能在肥胖致乳腺癌的过程中起重要作用。提供了一个为什么肥胖症与乳腺癌相关的解释。     

瘦素在乳腺癌发病中的作用

瘦素是一种由肥胖基因(ob基因)编码表达的小分子蛋白,在调控机体的摄食行为和脂肪代谢方面具有重要作用.近来大量研究发现瘦素在体外可促进乳腺细胞转化、癌细胞增生并促进血管生成.这表明瘦素在乳腺癌的发生发展中可能起重要作用,但具体机制尚未阐明.本文主要从体外实验、动物试验和乳腺癌病理组织研究3方面对瘦素在乳腺癌发病中的作用的近年相关研究进展进行综述.     

瘦素在乳腺癌发病中的作用

瘦素是一种由肥胖基因(ob基因)编码表达的小分子蛋白,在调控机体的摄食行为和脂肪代谢方面具有重要作用.近来大量研究发现瘦素在体外可促进乳腺细胞转化、癌细胞增生并促进血管生成.这表明瘦素在乳腺癌的发生发展中可能起重要作用,但具体机制尚未阐明.本文主要从体外实验、动物试验和乳腺癌病理组织研究3方面对瘦素在乳腺癌发病中的作用的近年相关研究进展进行综述.     

瘦素在乳腺癌发病中的作用

瘦素是一种由肥胖基因(ob基因)编码表达的小分子蛋白,在调控机体的摄食行为和脂肪代谢方面具有重要作用.近来大量研究发现瘦素在体外可促进乳腺细胞转化、癌细胞增生并促进血管生成.这表明瘦素在乳腺癌的发生发展中可能起重要作用,但具体机制尚未阐明.本文主要从体外实验、动物试验和乳腺癌病理组织研究3方面对瘦素在乳腺癌发病中的作用的近年相关研究进展进行综述.     

瘦素与肾脏

瘦素是肥胖(ob)基因编码的一种蛋白激素，1994年ob基因及其表达产物瘦素的发现和1995年瘦素受体(ob—R)的发现，极大地推动了人们对肥胖及其相关疾病的认识。肾脏作为瘦素的清除器官及肾脏组织瘦素受体的发现，提示瘦素作为一种新发现的物质，在肾脏功能和肾脏病的发生和发展中可能发挥着重要的作用。     

磷酸三酯酶相关基因与肥胖关系的研究进展

肥胖已经成为严重危害人类健康的社会问题。目前已筛选到部分与肥胖相关的基因，其中磷酸三酯酶相关基因（phosphotriesteraserelatedgene，PTER）被认为与肥胖具有一定的相关性。PTER基因在脂肪组织中高表达，在脂肪的蓄积过程r11起到重要的作用，并且与肥胖的程度及其衡量指标有一定的相关性，PTER单核苷酸多态性（rsl0508503）与肥胖及各肥胖指征亦有明显的相关性。另外，PTER可导致体内瘦素浓度的变化，进一步促进肥胖的发生。本文在介绍PTER的发现及组织表达特性的基础上，综述了该基因与肥胖和瘦素的关系，并对其今后的研究方向做一展望。     

瘦素及瘦素受体在乳腺癌中的表达及临床意义

目的 探讨瘦素及其受体mRNA及蛋白的表达在乳腺癌发生、发展中的意义。方法 采用巢式逆转录-聚合酶链反应〈RT-PCR）和免疫组织化学方法检测39例乳腺癌及其周围正常乳腺组织瘦素及其受体的mRNA及蛋白表达，分析乳腺癌组织瘦素与瘦素受体表达的相关性及其与临床病理之间的关系。结果 瘦素mRNA及蛋白在正常乳腺及乳腺癌组织阳性表达率均为100．00％；瘦素受体mRNA和蛋白在乳腺癌组织阳性表达率为74．40％。正常乳腺组织mRNA阳性表达率7．69％；瘦素及其受体在乳腺癌组织的表达量高于正常组织。差异具有统计学意义（P〈0．01）；瘦素受体的表达与瘦素表达明显相关（P〈0．01）。瘦素及瘦素受体高表达与乳腺癌的转移及浸润明显相关（P〈0．01）。结论 瘦素在乳腺癌的发生发展中可能起着促进作用，瘦素及其受体表达情况可以作为乳腺癌诊断或预后的指标。     

瘦素与胃肠运动

瘦素是由肥胖基因编码、脂肪细胞分泌的一种蛋白质类激素,在调节摄食、体重、能量消耗和神经内分泌方面发挥着重要的作用.研究证实,瘦素可以改变胃肠神经肌肉的反应性,从而调节胃排空及肠动力.表明瘦素是与胃肠的生理功能及胃肠疾病密切相关的一种新的胃肠激素.本文就瘦素与胃肠运动的关系进行简要综述.     

慢性肾脏疾病肾功能异常者血清瘦素水平的变化

瘦素（LEP）是肥胖基因（Ob gene）编码的相对分子质量为16700的多肽类激素。瘦素具有重要生理作用,其水平变化与肾脏关系密切。本文探讨慢性肾衰竭与LEP的关系及发生机制,报道如下。     

Vasopressor hormone response following mesenteric traction during major abdominal surgery

Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI₂) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI₂), TXB₂ (stabile metabolite of thromboxane A₂) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI₂ release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF_1α (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB² (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI₂ release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A₂, presumably contributing to hemodynamic stability within 30 min after MT.     

A Teaspoon Pump for Pumping Blood with High Hydraulic Efficiency and Low Hemolysis Potential

Abstract: Virtually all blood pumps contain some kind of rubbing, sliding, closely moving machinery surfaces that are exposed to the blood being pumped. These valves, internal bearings, magnetic bearing position sensors, and shaft seals cause most of the problems with blood pumps. The original teaspoon pump design prevented the rubbing, sliding machinery surfaces from contacting the blood. However, the hydraulic efficiency was low because the blood was able to "slip around" the rotating impeller so that the blood itself never rotated fast enough to develop adequate pressure. An improved teaspoon blood pump has been designed and tested and has shown acceptable hydraulic performance and low hemolysis potential. The new pump uses a nonrotating "swinging" hose as the pump impeller. The fluid enters the pump through the center of the swinging hose; therefore, there can be no fluid slip between the revolving blood and the revolving impeller. The new pump uses an impeller that is comparable to a flexible garden hose. If the free end of the hose were swung around in a circle like half of a jump rope, the fluid inside the hose would rotate and develop pressure even though the hose impeller itself did not "rotate"; therefore, no rotating shaft seal or internal bearings are required.     

Microspheres Based Detoxification System: A New Method in Convective Blood Purification

Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.     

Tissue perfusion in relation to cardiac output during continuous positive-pressure ventilation and administration of propranolol or verapamil

Background : Our objective was to determine whether administration of propranolol or verapamil modifies the hemodynamic adaptation to continuous positive-pressure ventilation (CPPV), in particular the regional distribution of cardiac output (CO).
Methods : General hemodynamics and regional blood flows assessed by microsphere technique (15 (μm) were recorded in 16 anesthetized pigs during spontaneous breathing (SB) and CPPV with 8 cm H₂O end-expiratory pressure (CPPV8) before and after intravenous administration of propranolol (0.3 mg · kg⁻¹ followed by 0.15 mg · kg⁻¹ · h⁻¹, n=8) or verapamil (0.1 mg · kg⁻¹ followed by 0.3 mg · kg⁻¹ · h⁻¹, n=8).
Results : CPPV8 depressed CO by 25% without shifts in its relative distribution with the exception of a noteworthy increase in adrenal perfusion. Propranolol increased arterial blood pressure, and due to a fall in heart rate, CO dropped by 25%. The kidneys and, to a lesser extent, the splanchic region and central nervous system received increased fractions of the remaining CO at the expense of skeletal muscle flow. Similar patterns were seen during SB and CPPV8 such that the combination of propranolol and CPPV8 depressed CO by 50%. The circulatory effects of verapamil were less evident but myocardial perfusion tended to increase.
Conclusions : The combination of propranolol or verapamil with CPPV does not result in any specific hemodynamic interaction in anesthetized pigs, except that the combined effect of propranolol and CPPV may severely reduce CO.     

Bariatric Surgery in Some "Central and East-European (former Eastern bloc)"Countries - Current Status and Prediction for the Next Millennium

Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.     

Volatile anaesthetics reduce adhesion of blood platelets under low-flow conditions in the coronary system of isolated guinea pig hearts

Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.     

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits

Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg^?1 i. v. and 32 μg · kg^?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg^?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg^?1. The mean ED₅₀s, calculated from dose-response curves, were 5.4 mg · kg^?1, 3.9 μg · kg^?1 and 0.4 mg · kg^?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg^?1 and 8 μg · kg^?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.     

Influence of dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery

Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg^?1 · min^?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min^?1 · m^?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO₂I) and oxygen consumption index (VO₂I) were also significantly increased in the dopexamine group (DO₂I: from 416±91 to 717±110 ml/m² · m²; VO₂I: from 98±25 to 157±22 ml/m² · m²), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.     

A comparison of the inhibitory effects of four volatile anaesthetics on the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits

Background: Halothane inhibits in vitro and in vivo activity of cytochrome P-450 (CYP) 2E1. There are several fluorinated volatile anaesthetics besides halothane, and most of them are defluorinated by CYP2E1. It is unclear whether other fluorinated anaesthetics inhibit the in vivo activity of CYP2E1.
Methods: We compared the inhibitory effects of therapeutic concentrations of four inhalational anaesthetics, halothane, enflurane, isoflurane, and sevoflurane, on chlorzoxazone metabolism in rabbits receiving artificial ventilation.
Results: All four inhalational anaesthetics decreased arterial blood pressure and increased plasma chlorzoxazone concentration. However, no significant differences in the plasma chlorzoxazone concentration were found between the four anaesthetics. The estimated chlorzoxazone clearance increased after beginning inhalation with all four agents, but no significant difference in clearance was noted between agents.
Conclusions: At therapeutic concentrations, the in vivo inhibitory effect on chlorzoxazone metabolism was similar for all four inhalational anaesthetics examined, even though their chemical characteristics and extent of hepatic metabolism differ considerably.     

Systemic analgesia adapted to the children's condition

A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be used in patients with pre-existing illnesses. NSAIDs are the most effective treatment for acute pain of moderate intensity in children; however, these drugs should be avoided in patients at increased risk for serious side effects, e.g. patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs can be given with minimal risks to the younger child with mild to moderate asthma, and, in these patients, the use of steroids can be encouraged; in addition to their antiemetic and analgesic action, a beneficial effect on asthma symptoms can be expected. In the non-intubated child with cerebral trauma, exaggerated sedation caused by opioids and increased bleeding tendency caused by NSAIDs must be avoided. In neonates and small infants, the oral administration of sucrose or glucose is helpful to minimize pain reaction during short uncomfortable interventions.