骨髓脂肪的分析技术及其与骨质疏松关系的研究进展

骨质疏松（osteoporosis，OP）是一种公共卫生健康疾病，不仅增加了国家医疗卫生系统的负担，并且降低了人们的生活质量。既往关于OP的研究主要集中于骨骼的矿化部分，认为骨髓脂肪为惰性的组成成分。但是，近年越来越多的研究发现骨髓脂肪通过内分泌和旁分泌作用能够影响骨量与骨质量。为了明确骨-骨髓脂肪的相互作用以及OP的发生机制，学者们通过许多手段对骨髓脂肪的成分进行量化并探索其功能，有助于进一步明确骨髓脂肪代谢在OP形成过程中的可能机制。质子磁共振波谱（MRS）以及MRI水脂分离成像弥补了质谱技术的缺点，可以无创的检测活体骨髓脂肪，MRS能够分析单个体素的脂肪分数以及不同脂肪酸成分相对含量，而MRI水脂分离成像能够分析脂肪的空间分布并得出其脂肪分数。目前骨髓脂肪与骨质疏松关系研究主要集中于体外实验，如何在活体内研究其作用机制仍需进一步探索。骨髓脂肪酸参与骨质疏松的发病机制可能成为治疗骨质疏松的潜在靶点，未来需要进一步明确健康骨骼各种重点脂肪酸的实际需要量，从而改善日常饮食，保护骨骼。本文就骨髓脂肪的分析技术及其与骨质疏松的关系研究进展进行综述。     

脂质代谢紊乱和骨质疏松

骨质疏松或骨量减少与脂质代谢紊乱常并存,它们之间的关系日益受到研究者的关注.现在研究提示,过氧化物酶体增殖物激活受体γ(PPAR7)等因子有可能在两者的发病机制中起到关键作用,并且脂质代谢紊乱导致的骨髓脂肪增多可能是导致骨髓微循环障碍和骨量减少的主要原因.能够同时纠正脂质代谢紊乱和防治骨质疏松的药物是目前药理学研究的热点之一.笔者就脂质代谢紊乱和骨质疏松的关系进行简要综述.     

脂肪因子chemerin与骨质疏松症的关系展望

骨质疏松症是世界常见病、多发病,医学界对骨质疏松症发病机理与防治的研究愈显重要。近年研究表明,各种原因导致的骨量减少常伴有骨髓中脂肪组织含量的增加。骨质疏松的发生可能与骨代谢中成脂和成骨的比例有关。骨髓中脂肪组织在骨形成和造血支持中发挥重要作用,脂肪组织具有内分泌调节功能,释放出一系列重要的分泌性因子,比如：leptin、adiponectin、chemerin、resistin、visfatin等,在调节骨髓间充质干细胞向脂肪细胞分化过程中起关键作用。chemerin是新发现的脂肪因子,它在免疫应答、脂质代谢、糖类代谢、炎症反应等生理病理过程中都起着重要的作用。它与leptin、adiponect等脂肪因子一样参与骨代谢的调节,对维持骨代谢的平衡起着重要的作用。chemerin及其受体CMKLR1信号传递通路的激活可以调节骨髓间充质干细胞的分化,促进破骨细胞的生成,从而影响影响骨的重建。现在chemerin/CMKLR1信号通路影响骨代谢的作用机制还不是很明确,深入研究chemerin及其受体与骨质疏松的关系,可以进一步了解骨质疏松症发生机制,为治疗及预防骨质疏松症及提供了新的方向。     

脂肪因子 chemerin 与骨质疏松症的关系展望

骨质疏松症是常见病、多发病,医学界对骨质疏松症发病机理与防治的研究愈显重要。近年研究表明,各种原因导致的骨量减少常伴有骨髓中脂肪组织含量的增加。骨质疏松的发生可能与骨代谢中成脂和成骨的比例有关。骨髓中脂肪组织在骨形成和造血支持中发挥重要作用,脂肪组织具有内分泌调节功能,释放出一系列重要的分泌性因子,比如：leptin、adiponectin、chemerin、resistin、visfatin等,在调节骨髓间充质干细胞向脂肪细胞分化过程中起关键作用。 Chemerin是新发现的脂肪因子,它在免疫应答、脂质代谢、糖类代谢、炎症反应等生理病理过程中都起着重要的作用。它与leptin、adiponect 等脂肪因子一样参与骨代谢的调节,对维持骨代谢的平衡起着重要的作用。 Chemerin及其受体CMKLR1信号传递通路的激活可以调节骨髓间充质干细胞的分化,促进破骨细胞的生成,从而影响骨的重建。现在chemerin／CMKLR1信号通路影响骨代谢的作用机制还不是很明确,深入研究chemerin及其受体与骨质疏松的关系,可以进一步了解骨质疏松症发生机制,为治疗及预防骨质疏松症提供了新的方向。     

骨髓基质细胞成脂肪分化的研究进展

实验与临床研究证明，骨髓基质细胞成脂肪分化与骨质疏松存在着不可忽视的关系。在去卵巢或类固醇诱发的骨质疏松的动物模型均发现，骨量的丢失伴有骨髓腔内的脂肪细胞的数目大大增加。各种原因导致的骨质疏松患者中，骨髓腔内的脂肪细胞与松质骨的骨量成反比。对成纤维细胞克隆形成单位（CFU-Fs）的分析表明，9月龄大鼠骨髓中的基质干细胞数量明显少于6月龄大鼠，提示了骨髓基质细胞数量的减少和髓内脂肪细胞的增多存在某种关系。     

影响MSCs向成骨与成脂肪分化因素的研究进展

骨髓间充质干细胞是多能干细胞,通过诱导可分化成为骨、软骨、脂肪、肌腱等,其中影响其向成骨与成脂肪分化的因素很多。机体老化会使整体内环境发生巨大改变,也使骨髓内微环境与复杂的细胞内、外信号调控发生改变。控制相关的影响因素有助于诱导成骨分化而抑制成脂肪分化,进而提高骨质疏松、骨缺损和骨量丢失等相关疾病的治疗。     

骨髓基质干细胞成骨-成脂分化及补肾中药对其影响的研究进展

骨髓基质干细胞在不同条件的诱导下，可以分化为成骨细胞、软骨细胞、成纤维细胞、脂肪细胞、神经细胞等多种细胞系，在骨髓微环境中骨和脂肪形成之间的关系是复杂的，成骨细胞与脂肪细胞均来源于骨髓基质干细胞 (MSCs)，并且在其向成骨细胞和脂肪细胞分化之间存在相互逆转的关系和很大程度的可塑性。骨质疏松患者骨量减少与骨髓腔中脂肪组织增加有关，这可能与骨髓中MSCs分化失衡，过多向脂肪细胞分化有关。中医从“肾主骨”、“髓生骨”理论出发，认为肾精不足所致的骨髓空虚是骨质疏松症发病的关键，补肾中药通过影响骨髓基质干细胞成骨-成脂分化，从而防止骨质疏松症的发生。     

肌肉组织和脂肪组织对绝经后女性骨密度及骨强度的影响及作用机制

目的 探讨肌肉组织和脂肪组织对绝经后女性骨密度及骨强度的影响及作用机制。方法 检索近10年来研究绝经后女性肌肉和（或）脂肪对骨密度和（或）骨强度的影响的专业文献以及研究肌肉、脂肪和骨骼相互影响的具体机制的实验报告, 综合分析肌肉组织和脂肪组织对绝经后女性骨密度及骨强度的影响及作用机制。结果 多数研究表明肌肉组织含量及肌力可能是骨密度和骨强度的重要决定因素,骨髓脂肪会对骨骼产生不利影响,而髓外脂肪对骨密度及骨强度的影响则尚未达成一致认识;无论是肌肉组织还是脂肪组织,均可通过力学作用和化学调节两方面影响骨代谢,从而影响骨密度和骨强度,但其具体机制尚未完全阐明。结论 ①肌肉组织是骨密度及骨强度的重要影响因素,其在力学因素和化学调节等多方面对骨骼 起到正向保护作用,但具体机制尚需进一步研究。②骨髓脂肪增多与骨质疏松症负性相关已被认可,而髓外脂肪组织对骨密度及骨强度影响较为复杂,有待进一步研究探讨。③对于绝经后女性而言,通过合理锻炼和饮食等方式维持肌肉含量和肌力以及一定范围的体脂,对防治骨质疏松有重耍的积极意义。     

骨关节炎和骨质疏松：骨髓间充质干细胞与成骨细胞

骨关节炎和骨质疏松是最常见的两种骨代谢异常疾病。骨髓间充质干细胞和成骨细胞广泛存在于骨髓及松质骨中,对骨代谢有重要作用。本文对近年关于骨髓间充质干细胞和成骨细胞与这两种疾病关系的研究结果进行一综述,分析这两类细胞在不同骨代谢异常中的特点,以此增加对骨关节炎和骨质疏松发病机制的认识,希望能为临床更有针对性诊疗和预防骨代谢异常疾病提供一定帮助。     

移植治疗骨质疏松研究进展

随着人口老龄化,我国已居世界骨质疏松症患者数量的首位。目前针对原发性骨质疏松的治疗大部分是通过药物改善症状,尚没有研究出快速而确切的疗法。本文综述了近十年来对于骨质疏松发病机制和新的治疗方法探索的新进展。其中,从细胞水平对骨质疏松的发病机制研究表明,骨质疏松的发生与干细胞机能紊乱密切相关。干细胞以及骨髓基质机能紊乱以及功能不足,导致多种促进成骨的因子生成不足,引起成骨细胞生成障碍、破骨细胞和脂肪细胞生成活跃,进而导致骨量减少、骨组织显微结构的异常形成骨质疏松。对于骨质疏松细胞水平发病机制的研究,促使了包括骨髓移植、干细胞移植、成骨细胞移植在内的应对骨质疏松新策略的产生。研究者尝试补充功能结构完整的骨髓、骨髓基质、干细胞、成骨细胞等进入骨质疏松者体内,从而调节机能紊乱、补足功能和成骨诱导生长因子的不足,以此达到预防和治疗骨质疏松的目的。     

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 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.     

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.     

Is the recovery profile of mivacurium independent of the rate of decay of its plasma concentration in patients with normal plasma cholinesterase activity?

Background: The duration of action of muscle relaxants is poorly correlated to the rate of decay of their plasma concentration. The plasma concentration of mivacurium may rapidly decrease below its active concentration because of the extensive hydrolysis of mivacurium. By inflating a tourniquet on one upper limb for 3 min after the administration of atracurium, mivacurium or vecuronium, we studied the influence of the initial decline of their plasma concentration on their effect. Methods: In 50 patients anaesthetised with thiopental, isoflurane and fentanyl, the effect of bolus doses of 0.15 or 0.25 mg . kg^?1 mivacurium (MIV 15, MIV 25), 0.3 or 0.5 mg . kg^?1 atracurium (ATR 30, ATR 50) and 0.06 or 0.1 mg . kg^?1 vecuronium (VEC 06, VEC 10) were measured on both arms (evoked response of the adductor pollicis to train-of-four stimulation every 12 s), a tourniquet being applied on one arm just before and during 3 min after the muscle relaxant bolus. Results: Tourniquet inflation of 3 min almost abolished the neuromuscular effect of mivacurium. In the vecuronium groups and in the ATR 50 group, tourniquet inflation did not modify the maximum degree of depression of the twitch response. Also, the duration of action of vecuronium was unaffected by the tourniquet. In the ATR 30 group, times to return of the twitch response to 25% (duration 25%) and 75% (duration 75%) of control response were significantly shorter in the cuffed arm, 23 min vs 27 min, and 41 min vs 45 min, respectively. In the ATR 50 group, only duration 25% was significantly shorter in the cuffed arm (41 min vs 45 min). Conclusion: The results suggest that the rate of decline of the plasma concentration of mivacurium is so rapid, that a very low and almost clinically ineffective concentration is present as soon as 3 min after its administration. The results also indicate that the recovery from a mivacurium-induced neuromuscular blockade is not influenced by the rate of decay of its plasma concentration in patients with genotypically normal plasma cholinesterase.     

Membranes in Artificial Organs

Abstract: Membrane processes play a pivotal and enabling role in modern replacement therapy for acute and chronic organ failure and in the management of immunologic diseases. In fact, virtually all contemporary extracorporeal blood purification methods employ membrane devices, and the next generation of artificial organs and tissue engineering therapies are almost certain to be similarly grounded in membrane technology. In this short essay, we comment on the similarities and differences among synthetic membranes and their natural counterparts and also provide a critical overview of the demographics and technology of hemodialysis, hemofiltration, apheresis, oxygenation, and emerging membrane technologies and applications.     

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.     

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.     

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.     

Dilemma of Membrane Biocompatibility and Reuse

Abstract: Numerous articles have been published on the multiple use of dialyzers and on the effect of different reprocessing chemicals and techniques on the dialyzer biocompatibility and performance. The results often appear contradictory, especially those comparing standard biocompatibility parameters. Despite this confusion, a discerning review of the published works allows certain limited conclusions to be drawn. Reprocessing of used hemodialyzers changes the biocompatibility profile of a dialyzer as defined by the parameters complement activation. leukopenia, and cytokine release. The effect of reprocessing depends on the chemicals and reprocessing technique applied and also on the type of membrane polymer being subjected to the reprocessing procedure. Reports of pyrogenic reactions indicate that the flux of the membrane also influences how suitable it is for safe reuse. An increased risk of allergic and pyrogenic reactions appears to be associated with dialyzer reuse. Furthermore, there has been a lack of investigations into the immunologic effect of the layer of adsorbed and chemically altered proteins that remains on the inner surface of reprocessed dialyzers. We conclude that the clinical benefit of dialyzer reuse cannot be generally accepted from a biocompatibility point of view.