Effects of tryptophan depletion on central and peripheral chemoreflexes in man

Klein (Arch. Gen. Psychiatry 50, 306-317, 1993) suggests that panic attacks are the result of a defective 'suffocation alarm' threshold that presents with carbon dioxide (CO(2)) hypersensitivity, exaggerated ventilatory response and panic in panic disorder (PD) patients. Serotonergic deficiencies enhance this ventilatory response in PD patients, as per 'suffocation alarm' theory predictions, suggesting that serotonin (5-HT) normalizes the ventilatory response. Other research supports a serotonin system-mediated stimulation of ventilation. Knowledge of 5-HT's role on ventilatory output and its neurophysiological sources impacts on the 'suffocation alarm' theory validity and predictive value. We used tryptophan depletion (TRP-) in concert with a modified Read rebreathing test to determine the effect of deficient serotonergic modulation on the central and peripheral chemoreflex threshold and sensitivity of response to CO(2) in 11 healthy men. TRP- did not affect central or peripheral chemoreflex threshold or sensitivity of response to CO(2). However, basal ventilation was significantly elevated during TRP-. In contrast to 'suffocation alarm' theory predictions, decreased 5-HT neurotransmission does not significantly affect the respiratory chemoreflex response to CO(2), impacting on non-chemoreflex drives to breathe. Panic associated respiratory abnormalities may be related to defective 5-HT modulation of non-chemoreflex drives to breathe, unrelated to any respiratory chemoreflex abnormality.     

Cardiovascular and respiratory mechanisms in anaphylactic and anaphylactoid shock reactions

Summary Different mediators such as histamine, leukotrienes, prostaglandins and bradykinin are involved in different reaction mechanisms such as cytotropic anaphylaxis (CA), immune complex anaphylaxis (ICA), reactions due to direct histamine liberation or activation of the complement system or hyperosmolarity induced anaphylactoid reactions.In the monkey CA induces systemic vasodilatation, a transient pulmonary hypertension and increase of cardiac output followed by peripheral blood pooling and depression of cardiac output. ICA induces peripheral vasoconstriction, a severe increase in pulmonary vascular resistance and decreased cardiac output, the latter possibly being partially due to decreased cardiac contractility.In hypersensitivity reactions in man cutaneous vasodilatation as well as vasoconstriction may occur alternatively. Peripheral blood pooling and increased vascular permeability are the cause of severe relative and absolute hypovolemia, respectively. Pulmonary vasoconstriction seems to occur in connection with serious bronchospasm. Decreased venous return, myocardial ischemia and hypoxemia can contribute to a reduction of cardiac performance. The most frequent changes in the ECG are sinus tachycardia, sinus bradycardia, extrasystoles, conduction disturbances as A-V block and bundle branch block; lethal or sublethal shock is often associated with malign arrhythmias or cardiac arrest.Almost normal blood gas values are seen in anaphylactic shock without clinical signs of respiratory obstruction. The very few documented cases of anaphylactic shock with respiratory obstruction indicate that increased airway resistance and reduced lung compliance may be present as well as mild to moderate hypoxemia with normal or subnormal CO₂ values.     

消退素D2对椎间盘突出所致根性神经痛的作用

目的 观察消退素D2（RvD2）对非压迫性腰椎间盘突出症所致根性神经痛模型大鼠的影响。 方法 选取雄性Sprague-Dawley(SD)大鼠36只,按随机数字表法分为假手术组,模型组和RvD2组,每组大鼠12只。模型组和RvD2组均采用自体髓核组织填充法制作非压迫性腰椎间盘突出症模型,假手术组仅暴露相应手术部位,不作其它处理。造模成功后连续3d对假手术组和模型组均鞘内给予磷酸盐缓冲液（PBS）10μl,RvD2组则鞘内给予RvD2溶液10ng/10μl。于造模前1d和造模成功后连续7d观察3组大鼠术侧的50%缩足阈值（PWT）,并于造模成功后第7天获取大鼠术侧L4至L6节段脊髓背角,采用蛋白质印迹法测定磷酸化的蛋白激酶B(p-AKT),蛋白激酶B(t-AKT),磷酸化的糖原合成激酶3β(p-GSK-3β)和糖原合成激酶3β(GSK-3β)的蛋白表达量,并用酶联免疫吸附试验测定肿瘤坏死因子α（TNF-α）、白介素-6（IL-6）、转化生长因子-β1（TGF-β1）和白介素-10（IL-10）的蛋白表达含量。 结果 造模成功后第1～7天,模型组和RvD2组大鼠50%PWT与假手术组同时间点比较,差异均有统计学意义（P<0.05）;造模成功后第3～7天,RvD2组的50%PWT分别为（6.31±2.11）g、（7.37±1.58）g、（7.96±1.73）g、（8.46±1.55）g、(8.55±1.44)g,与模型组同时间点比较,差异均有统计学意义（P<0.05）。造模成功后第7天,模型组和RvD2组的p-AKT和p-GSK-3β蛋白阳性表达水平与假手术组比较,差异有统计学意义（P<0.05）;且RvD2组的p-AKT和p-GSK-3β蛋白阳性表达水平与模型组比较,差异亦有统计学意义(P<0.05)。造模成功后第7天,模型组和RvD2组大鼠脊髓背角促炎细胞因子TNF-α和IL-6以及抗炎因子TGF-β1和IL-10的蛋白表达水平与假手术组比较,差异均有统计学意义（P<0.05）; 且RvD2组促炎细胞因子TNF-α和IL-6以及抗炎因子TGF-β1和IL-10的蛋白表达水平与模型组比较,差异均有统计学意义（P<0.05）。 结论 RvD2可减轻非压迫性椎间盘突出大鼠的根性神经痛,其机制可能与抑制GSK-3β活性,下调促炎因子以及上调抗炎因子的蛋白表达水平相关。     

Mechanisms of change in interpersonal therapy (IPT)

Although interpersonal therapy (IPT) has demonstrated efficacy for mood and other disorders, little is known about how IPT works. We present interpersonal change mechanisms that we hypothesize account for symptom change in IPT. Integrating relational theory and insights based on research findings regarding stress, social support, and illness, IPT highlights contextual factors thought to precipitate and maintain psychiatric disorders. It frames therapy around a central interpersonal problem in the patient's life, a current crisis or relational predicament that is disrupting social support and increasing interpersonal stress. By mobilizing and working collaboratively with the patient to resolve this problem, IPT seeks to activate several interpersonal change mechanisms. These include: 1) enhancing social support, 2) decreasing interpersonal stress, 3) facilitating emotional processing, and 4) improving interpersonal skills. We hope that articulating these mechanisms will help therapists to formulate cases and better maintain focus within an IPT framework. Here we propose interpersonal mechanisms that might explain how IPT's interpersonal focus leads to symptom change. Future work needs to specify and test candidate mediators in clinical trials. We anticipate that pursuing this more systematic strategy will lead to important refinements and improvements in IPT and enhance its application in a range of clinical populations.     

Association between Plasma Leptin Level and Systemic Inflammatory Markers in Patients with Aggressive Periodontitis

Background:

Increasing evidence supports an association between periodontitis and systemic diseases. Leptin is involved both in the energy metabolism and inflammatory processes and is suggested to be a link between periodontal infection and systemic health. The present study aimed to evaluate the peripheral leptin concentration in patients with aggressive periodontitis (AgP) and to explore the relationship between leptin and systemic inflammation.

Methods:

Ninety patients with AgP visiting the Clinic of the Periodontology Department, Peking University School and Hospital of Stomatology between July 2001 and May 2006, and 44 healthy controls (staff and student volunteers in the same institute) were recruited. Plasma levels of leptin and inflammatory cytokines including interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) were measured by enzyme-linked immunosorbent assay. Correlation and multiple linear regression analysis were performed to analyze the association between plasma leptin level and other variables.

Results:

Plasma leptin level of AgP group was significantly higher than that of the control group (19.7 ± 4.4 ng/ml vs. 7.5 ± 1.3 ng/ml, P < 0.01). After controlling for age, gender, and body mass index, positive correlation was observed between plasma leptin concentration and log-transformed levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α and CRP), and the partial correlation coefficients ranged from 0.199 to 0.376 (P < 0.05). Log-transformed IL-1β and IL-6 levels entered the final regression model (standardized β were 0.422 and 0.461 respectively, P < 0.01).

Conclusions:

Elevated plasma leptin concentration may be associated with increased systemic levels of inflammatory markers in AgP patients.     

Mechanisms of exercise-induced asthma

In a previous review in this journal McFadden eloquently presented the findings which led him and his colleagues to propose that respiratory heat loss and the subsequent cooling of the airways are the initial reaction sequence leading to airway obstruction in hyperventilation and exercise-induced asthma [62]. He further concluded that: “Exercise per se is not essential and serves only as means to increase ventilation”. Our interpretation of currently available data has led us to conclude that while respiratory heat loss may play an important permissive role in initiating the bronchoconstriction which follows exercise, the weight of evidence indicates that exercise per se serves as the trigger mechanism and is not just a tool to increase ventilation. Moreover, we believe that the role of exercise in releasing chemical mediators has been established, although pathways by which the airway smooth muscle is affected are still uncertain.     

泼尼松联合甲氨喋啶治疗对系统性红斑狼疮患者炎症因子及免疫球蛋白表达水平的影响

[目的]探讨泼尼松联合甲氨喋啶治疗系统性红斑狼疮(SLE)患者对外周血清中的炎症因子白细胞介素-17(IL-17)和白细胞介素-23(IL-23)及免疫球蛋白表达水平的影响.[方法]在本院治疗的74例SLE患者,随机分为两组,各37例.对照组采用醋酸泼尼松治疗,观察组在对照组基础上联合甲氨喋啶治疗,3个月治疗后对患者治...     

热休克转录因子1在心肌及其他组织中的抗炎作用

人类的热休克转录因子1（HSF1）在多个器官组织中均有表达，参与调节热休克反应、诱导热休克蛋白的表达。它具有多种生物学功能，不仅能抗凋亡、保护缺血心肌细胞、抑制心肌纤维化、参与生长发育过程；而且还能对抗炎症反应，在心肌细胞炎症反应、肺部损伤和感染、内毒素血症、全身炎症反应综合征及其他炎症相关性疾病中发挥着举足轻重的作用。本文结合热休克反应和热休克蛋白，就HSF1在不同组织和病理过程中的抗炎作用、与各种炎性介质的关系及其相互作用的机制作一综述。