香草醛吸嗅对小鼠抑郁样行为的影响及其机制的探讨

目的：探讨香草醛吸嗅对抑郁症的调节作用及其可能的作用机制。方法：将60只雄性C57小鼠,采用孤养＋慢性不可预见性中等强度刺激（ CUMS）或嗅球毁损,制备抑郁症动物模型,造模成功后,将小鼠随机分为百忧解组、香草醛吸嗅组、模型组及嗅球毁损＋香草醛吸嗅组。观察小鼠治疗后各时间点的神经行为学变化、血浆5-HT浓度的变化及海马5-HT表达。结果：香草醛组治疗2周后悬尾实验、强迫游泳实验时间均明显缩短（P＜0．05）,4周后糖水消耗量明显增加（P＜0．05）;香草醛吸嗅明显提高小鼠5-HT血浆内含量及海马区表达（ P＜0．05）。结论：香草醛吸嗅可以改善抑郁症模型小鼠的神经行为学,提高小鼠5-HT血浆含量及其在海马区表达,其机制可能是经嗅觉通路影响体内5-HT环路,影响海马、杏仁核情绪中枢活动,从而达到抑郁症防治的作用。     

应激大鼠下丘脑5-羟色胺1A受体活性与促肾上腺皮质激素释放因子表达的关系

目的:观察连续单一应激(SPS)前阻断大鼠5-羟色胺1A(5-HT1A)受体下丘脑促肾上腺皮质激素释放因子(CRF)表达的改变,初步探讨5-HT1A受体活性与CRF表达的关系.方法:将健康雄性Wistar大鼠分为对照组、模型组和阻断组,模型组和阻断组给予SPS.阻断组在给予SPS应激前使用5-HT1A受体阻断剂WAY100635进行干预.采用免疫组织化学和逆转录聚合酶链式反应(RT-PCR)方法检测下丘脑CRF蛋白和mRNA的表达.结果:对照组、模型组和阻断组免疫阳性细胞吸光度分别为6.94±0.61、22.36±1.55和16.86±1.65,mRNA相对表达分别为0.72±0.07、2.08±0.06和1.16±0.11,模型组高于对照组,阻断组低于模型组.结论:5-HT1A受体活性与下丘脑CRF表达有关.     

运动预干预对睡眠剥夺大鼠学习记忆及海马nNOS表达的影响

目的:探讨跑台运动预干预对完全睡眠剥夺(TSD)大鼠空间学习记忆能力、海马单胺类神经递质水平和神经元型一氧化氮合酶(nNOS)表达的影响。方法:将40只大鼠随机分为对照组(CON)、运动组(EX)、完全睡眠剥夺组(TSD)及睡眠剥夺运动组(EX+TSD)。除CON组及TSD组大鼠,EX组和EX+TSD组大鼠进行跑台运动预干预4周,运动结束后建立大鼠72 h睡眠剥夺模型(小平台水环境法),然后运用八臂迷宫实验(ERM)评估大鼠空间学习记忆能力,用高效液相-电化学法检测大鼠海马单胺类神经递质多巴胺(DA)、去甲肾上腺素(NE)、5-羟色胺(5-HT)的表达水平,用免疫组化法检测海马一氧化氮合酶(nNOS)神经元的表达。结果:(1)与CON组比较,ERM实验中TSD组大鼠工作记忆错误次数(WME)、参考记忆错误次数(RME)均显著增多,正确反应的次数(CN)减少,完成八臂迷宫时间显著延长(P 0. 01);海马内DA及NE的水平均显著下降(P 0. 01),而5-HT的水平增加(P 0. 01),海马nNOS阳性细胞平均光密度显著增加(P 0. 01);(2)与TSD组比较,ERM实验中EX+TSD组大鼠WME及RME均显著减少,CN增多,完成八臂迷宫时间均显著缩短(P均0. 05); EX+TSD组海马DA的表达水平显著增加(P 0. 05),5-HT的表达水平下降(P 0. 05),NE的表达水平则无显著变化(P 0. 05),海马nNOS阳性细胞平均光密度显著下降(P 0. 05)。结论:规律的跑台运动预干预可以增强TSD大鼠的学习记忆能力,其机制可能与此运动下调大鼠海马内nNOS活性、减弱高浓度NO的神经毒性纠正TSD大鼠单胺类神经系统紊乱,对睡眠剥夺引起的海马神经元损害具有保护作用有关。     

嗅球摘除后大鼠内嗅皮质区神经元变化的实验研究

目的:建立嗅球摘除大鼠模型,观察模型大鼠内嗅皮质区神经元在1 d、3 d、7 d、14 d四个时间点的变化。模型组+茉莉花萃取物,观察大鼠14 d时神经元的变化。与模型组和空白组形成对照,初步探讨茉莉花萃取物通过嗅觉通路对神经元再生作用的可能。方法:嗅球摘除模型建立不同组别,通过尼氏染色观察大鼠内嗅皮质神经元变化,免疫组化观察大鼠内嗅皮质中神经递质的变化。结果:尼氏染色:模型组大鼠内嗅皮质中神经元在受损后1 d、3 d、7 d含量逐步下降;14 d含量明显增加,但仍略低于空白组;吸嗅组(模型组+茉莉花萃取物)内嗅皮质区神经元略高于空白组。免疫组化:模型组大鼠内嗅皮质中5-HT和DA在受损后1 d、3 d、7 d表达逐步减弱,14 d时表达增强,但仍弱于空白组;吸嗅组表达高于14 d,但仍弱于空白组。结论:受损神经被激活后,内嗅皮质有显著的神经再生潜力。初步证明茉莉花萃取物能够通过嗅觉通路加速神经元再生,其机制可能与内嗅皮质中单胺类神经递质的改变相关。     

糖尿病大鼠中枢胰岛素、谷氨酸脱羧酶抗体变化与外周关系的研究

目的:检测链尿佐菌素(STZ)诱导Ⅰ型糖尿病(1-DM)大鼠嗅球、下丘脑弓状核、海马、杏仁核及胰腺的胰岛素(Ins)、谷氨酸脱羧酶抗体(GADA)含量变化,探讨中枢神经系统在1-DM发病机制中的作用及与外周关系。方法:用STZ复制1-DM大鼠模型,测定正常对照组与1-DM大鼠4、6、8、10周的嗅球、弓状核、海马、杏仁核及胰腺Ins、GADA的含量变化,并作比较与相关分析。结果:正常大鼠嗅球的Ins含量显著高于弓状核、海马、杏仁核(P<0.01);1-DM大鼠8周组与10周组嗅球Ins含量最低,GADA含量最高;与4周组、6周组比较均有显著差异(P<0.01)。大鼠嗅球的Ins、GADA含量变化与胰腺含量呈显著正相关(r=0.9932,P<0.01;r=0.9637,P<0.01)。1-DM8周组嗅球、胰腺的Ins及GADA含量与10周组无显著差异(P>0.05)。结论:1-DM大鼠嗅球、弓状核、海马、杏仁核的Ins减少与GADA的增加,以嗅球为最显著,其变化与胰腺含量变化呈显著相关,可能与中枢神经系统参与1-DM的发病有关。嗅球在胰腺产生GADA,胰岛释放Ins减少,胰岛功能衰竭等过程中,可能有中枢调控作用。     

糖尿病大鼠中枢胰岛素、谷氨酸脱羧酶抗体变化与外周关系的研究

目的: 检测链尿佐菌素（STZ）诱导Ⅰ型糖尿病（1-DM）大鼠嗅球、下丘脑弓状核、海马、杏仁核及胰腺的胰岛素（Ins）、谷氨酸脱羧酶抗体(GADA)含量变化，探讨中枢神经系统在1-DM发病机制中的作用及与外周关系。方法: 用STZ复制1-DM大鼠模型，测定正常对照组与1-DM大鼠4、6、8、10周的嗅球、弓状核、海马、杏仁核及胰腺Ins、GADA的含量变化，并作比较与相关分析。结果： 正常大鼠嗅球的Ins含量显著高于弓状核、海马、杏仁核（P＜0.01）; 1-DM大鼠8周组与10周组嗅球Ins含量最低, GADA含量最高；与4周组、6周组比较均有显著差异（P＜0.01）。大鼠嗅球的Ins、GADA含量变化与胰腺含量呈显著正相关（r=0.9932, P＜0.01; r=0.9637, P＜0.01）。1-DM 8周组嗅球、胰腺的Ins及GADA含量与10周组无显著差异（P＞0.05）。结论: 1-DM 大鼠嗅球、弓状核、海马、杏仁核的Ins减少与GADA的增加，以嗅球为最显著，其变化与胰腺含量变化呈显著相关，可能与中枢神经系统参与1-DM的发病有关。嗅球在胰腺产生GADA，胰岛释放Ins减少，胰岛功能衰竭等过程中，可能有中枢调控作用。     

川芎挥发油解热作用及其对家兔下丘脑单胺类神经递质含量的影响[ HT5”SS

目的:探讨川芎挥发油(CH)解热作用及其机理.方法:采用家兔内毒素发热模型,腹腔注射高、中、低三个剂量CH,观察家兔直肠温度变化,然后以荧光分光光度法测定家兔下丘脑单胺类神经递质含量.结论:各剂量组均有明显的解热作用(P&lt;0.01)且在发挥解热作用的同时高剂量组家兔下丘脑组织中5-羟色胺(5-HT)、多巴胺(DA)含量增高(P&lt;0.05),去甲肾上腺素(NE)含量变化不明显,5-羟吲哚乙酸(5-HIAA)含量减少(P&lt;0.05).结论:CH具有解热作用,其机理之一,可能是CH引起下丘脑组织中5-HT含量的改变从而导致了NE与5-HT的比值改变,以及DA含量的改变,最终使体温调定点趋于正常.讨论:体温调节的单胺学说认为5-HT和NE在量上的动态平衡可保持体温的相对恒定.并且5-HT和NE的变化与体温变化之间存在种属差异.本实验结果表明,川芎挥发油在发挥解热作用的同时,能使家兔下丘脑5-HT含量升高,这与文献报道的大鼠结果不一致,作者认为可能是种属差异引起的.同时NE含量变化不明显,5-HT与NE的比例关系发生明显变化,这可能是其解热作用机理之一.5-HIAA含量的降低,可能是由于川芎挥发油抑制了单胺氧化酶使5-HT代谢率降低所致. 　　……     

被动吸烟对胎鼠海马神经元一氧化氮合酶表达的影响

目的观察孕鼠被动吸烟对胎鼠海马神经元一氧化氮合酶表达的影响,以期为探讨被动吸烟对子代危害的机制提供更多实验依据。方法将雌性大鼠随机分为对照组和实验组两组。实验组采用人工熏烟的方法建立被动吸烟模型,对照组不作处理。妊娠21日人工结束分娩,取胎鼠脑组织,进行一氧化氮合酶（NOS）免疫组化染色。高倍镜下对海马区观察并摄片,用图像分析软件Image-Pro Plus对两组切片进行光密度分析,观察其差别。结果 NOS在胎鼠海马区有表达,分布于海马神经元胞质内。计算机图像分析结果表明,与对照组比较,实验组海马NOS表达下降,统计结果有显著差异性（P〈0.05）。结论孕鼠被动吸烟使胎鼠海马NOS的表达下降,其可能为孕期被动吸烟导致子代学习记忆记忆功能下降的机制之一。     

足底电击应激对小鼠脑组织神经递质水平变化的影响

目的:分析足底电击应激对小鼠前额叶皮层、海马、杏仁核神经递质的影响。方法:选择健康雌性成年C57BL/6J小鼠,随机分为对照组和足底电击应激组。应激组给予不可逃避足底电击,隔日1次,持续14d。足底电击应激结束次日进行糖水偏爱实验评估小鼠抑郁样行为;提取小鼠前额叶皮层、海马、杏仁核,试剂盒检测谷氨酸和γ-氨基丁酸(GABA)含量,高效液相色谱方法检测去甲肾上腺素(NE)和5-羟色胺(5-HT)含量。结果:与对照组相比,足底电击应激小鼠糖水偏爱指数明显降低;足底电击应激小鼠杏仁核谷氨酸水平显著升高、前额叶皮层及海马GABA水平显著下降;前额叶皮层、海马谷氨酸及杏仁核GABA表达水平无显著差异;足底电击应激小鼠前额叶皮层5-HT、杏仁核NE水平显著升高;前额叶皮层、海马NE,以及海马、杏仁核5-HT表达水平无显著差异。结论:足底电击应激引起小鼠抑郁样行为,上调杏仁核谷氨酸、NE以及前额叶皮层5-HT的表达,下调前额叶皮层、海马GABA的表达。     

大鼠配对前吗啡成瘾和戒断对子代社会交往与下丘脑催产素表达的影响

为探讨大鼠配对前经历吗啡成瘾和戒断事件对成年子代鼠社会交往以及下丘脑室旁核催产素表达的影响,本研究按经典方法建立大鼠吗啡成瘾模型,戒断21d后雌雄配对分组。第1组:吗啡成瘾雄鼠和吗啡成瘾雌鼠;第2组:吗啡成瘾雄鼠和生理盐水雌鼠;第3组:生理盐水雄鼠和吗啡成瘾雌鼠;第4组(对照组):生理盐水雄鼠和生理盐水雌鼠。所生子代鼠8周时采用社会交往实验装置测试各组子代鼠的社会交往能力,免疫组化方法检测室旁核催产素的表达。结果显示,社会交往能力实验:交往的第一个10min内,第1、2、3组子代雄、雌鼠与无生命物体交往时间比第4组子代鼠均减少;第1、2、3组子代雄鼠与陌生鼠1交往时间比第4组子代雄鼠减少,子代雌鼠相比差异无显著性;在第二个10min内,第1、2、3组子代雄、雌鼠与陌生鼠2交往时间比第4组子代鼠均减少;同样第1、2、3组子代雄、雌鼠与陌生鼠1(已熟悉)交往时间比第4组子代鼠均减少。免疫组织化学结果:第1、2、3组子代雄、雌鼠室旁核催产素能神经元数目比第4组子代鼠均明显减少。以上结果提示,配对前亲代经历吗啡成瘾和戒断事件导致成年子代鼠社会交往能力下降,并且影响子代下丘脑室旁核催产素的表达。     

Opportunities and challenges in the prevention and control of cancer and other chronic diseases: children's diet and nutrition and weight and physical activity

OBJECTIVE: The purpose of this article is to review the role of behavioral research in disease prevention and control, with a particular emphasis on lifestyle- and behavior-related cancer and chronic disease risk factors--specifically, relationships among diet and nutrition and weight and physical activity with adult cancer, and tracking developmental origins of these health-promoting and health-compromising behaviors from childhood into adulthood. METHOD: After reviewing the background of the field of cancer prevention and control and establishing plausibility for the role of child health behavior in adult cancer risk, studies selected from the pediatric published literature are reviewed. Articles were retrieved, selected, and summarized to illustrate that results from separate but related fields of study are combinable to yield insights into the prevention and control of cancer and other chronic diseases in adulthood through the conduct of nonintervention and intervention research with children in clinical, public health, and other contexts. RESULTS: As illustrated by the evidence presented in this review, there are numerous reasons (biological, psychological, and social), opportunities (school and community, health care, and family settings), and approaches (nonintervention and intervention) to understand and impact behavior change in children's diet and nutrition and weight and physical activity. CONCLUSIONS: Further development and evaluation of behavioral science intervention protocols conducted with children are necessary to understand the efficacy of these approaches and their public health impact on proximal and distal cancer, cancer-related, and chronic disease outcomes before diffusion. It is clear that more attention should be paid to early life and early developmental phases in cancer prevention.     

Pain and Effusion and Quadriceps Activation and Strength

Context:

Quadriceps dysfunction is a common consequence of knee joint injury and disease, yet its causes remain elusive.

Objective:

To determine the effects of pain on quadriceps strength and activation and to learn if simultaneous pain and knee joint effusion affect the magnitude of quadriceps dysfunction.

Design:

Crossover study.

Setting:

University research laboratory.

Patients or Other Participants:

Fourteen (8 men, 6 women; age = 23.6 ± 4.8 years, height = 170.3 ± 9.16 cm, mass = 72.9 ± 11.84 kg) healthy volunteers.

Intervention(s):

All participants were tested under 4 randomized conditions: normal knee, effused knee, painful knee, and effused and painful knee.

Main Outcome Measure(s):

Quadriceps strength (Nm/kg) and activation (central activation ratio) were assessed after each condition was induced.

Results:

Quadriceps strength and activation were highest under the normal knee condition and differed from the 3 experimental knee conditions (P < .05). No differences were noted among the 3 experimental knee conditions for either variable (P > .05).

Conclusions:

Both pain and effusion led to quadriceps dysfunction, but the interaction of the 2 stimuli did not increase the magnitude of the strength or activation deficits. Therefore, pain and effusion can be considered equally potent in eliciting quadriceps inhibition. Given that pain and effusion accompany numerous knee conditions, the prevalence of quadriceps dysfunction is likely high.Key Words: arthrogenic muscle inhibition, central activation failure, voluntary activation, muscles

Key Points

• Knee pain and effusion resulted in arthrogenic muscle inhibition and weakness of the quadriceps.
• The simultaneous presence of pain and effusion did not increase the magnitude of quadriceps dysfunction.
• To reduce arthrogenic muscle inhibition and improve muscle strength, clinicians should employ interventions that target removing both pain and effusion.

Quadriceps weakness is a common consequence of traumatic knee joint injury^1,2 and chronic degenerative knee joint conditions.^3,4 Arthrogenic muscle inhibition (AMI), a neurologic decline in muscle activation, results in quadriceps weakness and hinders rehabilitation by preventing gains in strength.⁵ The inability to reverse AMI and restore muscle function can lead to decreased physical abilities,⁶ biomechanical deficits,⁷ and possibly reinjury.⁵ Furthermore, researchers^8,9 have suggested that quadriceps weakness resulting from AMI may place patients at risk for developing osteoarthritis in the knee. In light of the substantial influence of quadriceps AMI on these clinically relevant outcomes, we need to improve our understanding of the factors that contribute to this neurologic decline in muscle activity so efforts to target and reverse it can be implemented and gains in strength can be achieved more easily.Joint injury and disease are accompanied by numerous sequelae (ie, pain, swelling, tissue damage, inflammation), so ascertaining which one ultimately leads to neurologic muscle dysfunction is difficult. Whereas a joint effusion can result in AMI,^10–12 the effects of pain are less understood despite many clinicians attributing AMI to pain. Using techniques that introduce knee pain without accompanying injury may provide insights into the role of pain in eliciting AMI.The degree of knee joint damage may play a role in the quantity of AMI that manifests. Hurley et al^13,14 demonstrated that quadriceps AMI, measured using an interpolated-twitch technique, was greater in patients with extensive traumatic knee injury (eg, fractured tibial plateau, ruptured medial collateral ligament, and medial meniscectomy) than patients with isolated joint trauma (ie, isolated anterior cruciate ligament [ACL] rupture). Similarly, patients with more knee joint symptoms (ie, greater number of symptoms and increased severity of symptoms) may present with greater magnitudes of quadriceps inhibition. Recently, investigators¹⁵ have suggested that patients with more pain display less quadriceps strength, supporting this tenet. Given that effusion and pain often present simultaneously with joint injuries and diseases, such as ACL injury and osteoarthritis, examining both the isolated and cumulative effects of these sequelae appears warranted to determine if they influence the magnitude of muscle inhibition.Experimental joint-effusion and pain models are safe and effective experimental methods that allow for the isolated examination of their effects on muscle function. The effusion model, whereby sterile saline is injected directly into the knee joint capsule,⁷ produces a clinically relevant magnitude of the joint effusion that may be present with traumatic injury. Effusion is thought to activate group II afferents responding to stretch or pressure,^16–18 which in turn may facilitate group Ib interneurons and result in quadriceps AMI.⁵ The pain model involves injecting hypertonic saline into the infrapatellar fat pad to produce anteromedial knee pain similar to that described in patients with patellofemoral pain syndrome.¹⁹ Pain is considered to initiate AMI through activation of group III and IV afferents that act as nocioceptors to signal damage or potential damage to joint structures.^16–18 The firing of these afferents then may lead to facilitation of group Ib interneurons, the flexion reflex, or the gamma loop, ultimately resulting in quadriceps inhibition.²⁰ Thus, these models allow us to create symptoms that are associated with knee injury and have the added benefit of providing a way to examine their effects in isolation.Therefore, the purpose of our study was to determine the effects of pain on quadriceps strength and activation and to learn if simultaneous pain and knee joint effusion would affect the magnitude of quadriceps dysfunction. We hypothesized that pain alone would result in quadriceps inhibition and that the magnitude of inhibition would be greater when effusion and pain were present simultaneously.     

Postinfectious immunodeficiency and autoimmunity: pathogenic and clinical values and implications

Autoimmunity is still a mystery of clinical immunology and medicine as a whole. The etiology and pathogenesis of autoimmune disorders remain unclear and, thus, are assessed as a balance between hereditary predisposition, triggering factors and the appearance of autoantibodies and/or self-reactive T cells. Among the immunological armamentarium, molecular mimicry, based on self-reactive T- and B-cell activation by cross-reactive epitopes of infectious agents, is of special value. Hypotheses regarding the possible involvement of molecular mimicry in the development of postinfectious autoimmunity are currently very intriguing. They provide new approaches for identifying etiological agents that are associated with postinfectious autoimmunity, paired microbial- and tissue-linked epitopes targeted for autoimmune reaction determination, postinfectious autoimmunity pathogenesis recognition and specific prevention, and therapy for autoimmune disorder development.     

Beta-endorphin and drug-induced reward and reinforcement

Although drugs of abuse have different acute mechanisms of action, their brain pathways of reward exhibit common functional effects upon both acute and chronic administration. Long known for its analgesic effect, the opioid beta-endorphin is now shown to induce euphoria, and to have rewarding and reinforcing properties. In this review, we will summarize the present neurobiological and behavioral evidences that support involvement of beta-endorphin in drug-induced reward and reinforcement. Currently, evidence supports a prominent role for beta-endorphin in the reward pathways of cocaine and alcohol. The existing information indicating the importance of beta-endorphin neurotransmission in mediating the reward pathways of nicotine and THC, is thus far circumstantial. The studies described herein employed diverse techniques, such as biochemical measurements of beta-endorphin in various brain sites and plasma, and behavioral measurements, conducted following elimination (via administration of anti-beta-endorphin antibodies or using mutant mice) or augmentation (by intracerebral administration) of beta-endorphin. We suggest that the reward pathways for different addictive drugs converge to a common pathway in which beta-endorphin is a modulating element. beta-Endorphin is involved also with distress. However, reviewing the data collected so far implies a discrete role, beyond that of a stress response, for beta-endorphin in mediating the substance of abuse reward pathway. This may occur via interacting with the mesolimbic dopaminergic system and also by its interesting effects on learning and memory. The functional meaning of beta-endorphin in the process of drug-seeking behavior is discussed.     

PTEN与信号转导及肿瘤

ＴＥＮ[1] (ｐｈｏｓｐｈａｔａｓｅａｎｄｔｅｎｓｉｎｈｏｍｏｌｏｇｙｄｅｌｅｔｅｄｏｎｃｈｒｏｍｏｓｏｍｅｔｅｎ)又名ＭＭＡＣ1 [2 ] (ｍｕｔａｔｅｄｉｎｍｕｔｉｐｌｙａｄａｎｃｅｄｃａｎｃｅｒ 1 )和ＴＥＰ1 [3 ] (ＴＧＦ -βｒｅｇｕｌａｔｅｄａｎｄｅｐｉｔｈｅｌｉａｌｃｅｌｌ -ｒｉｃｈｅｄｐｈｏｓｐｈａｔａｓｅ 1 ) (以下均称为ＰＴＥＮ) ,是 1 997年由 3个研究小组先后发现的一个具有双特异磷酸酶活性的抑癌基因。ＰＴＥＮ基因异常广泛存在于人类多种恶性肿瘤 ,如恶性神经胶质瘤、前列腺癌、子宫内膜癌、黑色素瘤等…     

Tobacco and alcohol and the risk of head and neck cancer

Summary We carried out two case-control studies on the relative risk of head and neck cancer in association with tobacco and alcohol consumption. The first study carried out at the ENT Department of the University hospitals of Heidelberg and Giessen (FRG) comprised 200 male patients with squamous cell cancer of the head and neck and 800 control subjects matched for sex, age, and residential area (1:4 matching design). Of the tumour patients, 4.5% had never smoked, in contrast to 29.5% of the control group. The average tobacco and alcohol consumption of the patients was approximately twice as high as in the control subjects. The highest alcohol and tobacco consumption was observed in patients suffering from oropharyngeal cancer. Tobacco and alcohol increased the risk of head and neck cancer in a dose-dependent fashion and acted as independent risk factors. In heavy smokers (> 60 pack-years) a relative risk of 23.4 (alcohol adjusted) was calculated. Combined alcohol and tobacco consumption showed a synergistic effect. The risk ratio increased more in a multiplicative than in an additive manner. Oral and laryngeal cancer were associated with the highest tobacco-associated risk values. The highest ethanol-associated risk values were associated with oropharyngeal and laryngeal cancer. The second study was carried out at the ENT Department of the University of Heidelberg on 164 males with squamous cell carcinoma of the larynx and 656 control subjects matched for sex, age and residential area (1:4 matching design). Of the cases, 4.2% had never smoked, compared with 28.5% of the control subjects. The risk of laryngeal cancer by tobacco consumption was dose dependent, reaching a maximum value of 9.1 (adjusted for alcohol) for a consumption of more than 50 tobacco-years (TY). The relative risk of laryngeal cancer associated with alcohol intake was also dose dependent, reaching a value of 9.0 (adjusted for tobacco) for a mean daily consumption of more than 75 g alcohol. An analysis of subsite specific risks showed that heavy smokers (> 50 TY) carried a nearly ten times higher risk of supraglottic cancer than of glottic cancer. The risk of supraglottic cancer from alcohol consumption was also higher than that of glottic cancer.     

类赖氨酰氧化酶2与肿瘤转移和发生

类赖氨酰氧化酶2(lysyl oxidase-like 2,LOXL2)是赖氨酰氧化酶(lysyl oxidase,LOX)基因家族的成员之一,其表达产物能促进胶原沉积.LOXL2的过表达能促进纤维化,并与肿瘤侵袭、转移及不良预后有关.目前大部分学者认为LOXL2是一种转移促进基因,也有实验支持其是一种肿瘤抑制基因.研究发现LOXL2可以通过激活Snail/Ecadherin通路或Src/FAK通路促进转移.LOXL2有望作为肿瘤生物标志物,用于预后判断,成为一个新的治疗靶点.     

Muscle strength and serum testosterone,cortisol and SHBG concentrations in middle-aged and elderly men and women

Forty healthy males (M) and females (F) divided into two different age groups i.e. M50 years (range 44–57; n= 9), F50 years (range 43–54; n= 9), M70 years (range 64–73; n= 11) and F70 years (range 63–73; n= 11) volunteered as subjects for examination of muscle cross-sectional area (CSA) and maximal voluntary isometric force production characteristics of the leg extensor muscles and serum androgen and sex hormone binding globulin (SHBG) concentrations. The CSA in the male groups was greatly larger (P < 0.01) than in the female groups and both elderly groups demonstrated slightly (n.s.) smaller values in the CSA than the two middle-aged groups. Maximal force of 2854 ± 452 N in M50 was greater (P < 0.05) than that of 2627 ± 752 N recorded for F50 as well as the force of 2787 ± 843 in M70 was greater (P < 0.001) than that of 1849 ± 295 recorded for F70. The force between F50 and F70 differed significantly (P < 0.05) from each other. The maximal rate of force production in M50 was greater (P < 0.01) than in F50 as well as in M70 greater (P < 0.001) than in F70. Both middle-aged groups demonstrated greater (P < 0.05) values than the respective elderly groups of the same sex. The individual values in the CSA correlated with the values in maximal force both in the middle-aged subjects (r= 0.66; P < 0.01) and in the elderly subjects (r= 0.69; P < 0.01). The mean concentration of serum testosterone in M50 was slightly (n.s.) greater than in M70 and in F50 significantly (P < 0.05) greater than in F70. Serum SHBG levels were lower in the males (P < 0.01) than in the females and serum testosterone/SHBG ratio in M70 and in F70 were lower (P < 0.05) than in M50 and in F50, respectively. In the females significant positive correlations were observed between the individual values in serum testosterone concentration and the values both in the CSA (r= 0.46; P < 0.05) and in maximal force (r= 0.62; P < 0.01) as well as between serum testosterone/SHBG ratio and both the CSA (r= 0.55; P < 0.05) and maximal force (r= 0.68; P < 0.01). The present results imply that the decreasing basal level of blood testosterone over the years in aging people, especially in females, may lead to decreasing anabolic effects on muscles thus having an association with age-related declines in the maximal voluntary neuromuscular performance capacity in aging people.