Studies on the antiinflammatory,immunoregulatory, and analgesic actions of melatonin

In order to develop melatonin (MT) as a potential new drug for the treatment of diseases with inflammation, pain, and abnormal immune responses, the effects and mechanisms of MT on inflammation, immunoregulation, and nociception were studied systematically. MT (40–160 mg/kg, ip) had significant analgesic effects in the hot-plate, writhing, and tail-flick models, with a marked dose- and time-dependence. The onset of its analgesia about 30–60 min after ip, was slower than that of pethidine, but the duration was longer (about 1.5–2 h). The analgesia was also induced by icv MT (0.25 mg/kg) injection. A lower dose of MT (10 mg/kg) could enhance the analgesic effect of pethidine, which was blocked by naloxone (10 mg/kg). MT (100 mg/kg, ip) decreased the content of beta-endorphin in the hypothalamus and pituitary. The analgesia of MT could be attenuated by pretreatment with reserpine (30 mg/kg, ip) or phentolamine (10 mg/kg, ip). CaCl₂ (230 mg/kg) could antagonize the analgesia of MT. EGTA and verapamil had opposite effects to CaCl₂. No tolerance and dependence to MT was found in mice. Further studies showed that MT could enhance the functions of T and B lymphocytes and macrophages in vitro and in adjuvant arthritis, and inhibit the disturbance of immune cells. MT could inhibit the swelling of hindpaw induced by carrageenin and complete Freund's adjuvant. These factors suggest that MT possesses marked antiinflammatory, immunoregulatory, and analgesic effects which may be related to the system of opiate, monoamine, and Ca²⁺ modulation. Drug Dev. Res. 39:167–173. © 1997 Wiley-Liss, Inc.     

DOSE-RELATED EFFECTS OF RADIAL EXTRACORPOREAL SHOCK WAVE THERAPY FOR KNEE OSTEOARTHRITIS: A RANDOMIZED CONTROLLED TRIAL

ObjectiveTo assess the dose-related effects of radial extracorporeal shock wave therapy on pain alleviation in knee osteoarthritis.MethodsWith the use of a 2 × 2 factorial randomized controlled design, 89 patients diagnosed with knee osteoarthritis were assigned to 1 of 4 treatment groups, which varied in terms of shock intensity (0.12 mJ/mm², lower density, or 0.24 mJ/mm², higher density) and shock number (2,000 impulses or 4,000 impulses), or to a placebo control. Each group received 4 sessions of radial extracorporeal shock wave therapy, one week apart. The primary outcome was pain intensity measured on a visual analogue scale, and the secondary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score. Assessments were performed at baseline, after each session, and at 4-week follow-up.ResultsTwo-way repeated-measures analysis of variance revealed a significant effect on the Pain score for intensity (p < 0.001), with no effect for number (p = 0.467) or the intensity–number interaction (p = 0.536). Similar results were obtained for the WOMAC scores, except for an association between number and WOMAC score (p = 0.036). At the 4-week follow-up, all treatment groups showed greater reductions in the Pain and WOMAC scores than the control group. In addition, scores decreased more at higher densities of shock intensity than at lower densities, while there was no significant difference between the 2,000- and 4,000-shock conditions.ConclusionModerate-intensity radial extracorporeal shock wave therapy was effective, and a higher density might be more efficacious in alleviating pain in knee osteoarthritis.LAY ABSTRACTExtracorporeal shock wave therapy may be a viable treatment for knee osteoarthritis with local pain and dysfunction; however, there are no standards on how to choose the treatment parameters to obtain the best outcome. This study compared 5 different levels of amount of treatment in 89 patients with knee osteoarthritis, and found that a medium intensity of therapy was effective. In addition, a higher intensity of extracorporeal shock wave therapy, rather than higher shock numbers, might result in a higher level of alleviation of symptoms in these patients.Key words: dose-response relationship, radial extracorporeal shock wave therapy, knee osteoarthritis

Knee osteoarthritis (KOA) is the most common degenerative joint lesion; it has a high prevalence and a negative impact on the quality of life of affected individuals (1). It has been reported in a case–control study carried out in North Staffordshire that 9.6% of men and 18% of women have symptomatic KOA at the age of 60 years and over (2). In addition, approximately 25% of the population older than 55 years reports at least one episode of knee pain each year in the United Kingdom.(3). The management of early- medium stage KOA is crucial; the main aims during this stage of conservative therapy for KOA are to relieve pain and enhance joint mobility (4, 5). Treatments for KOA include oral medication, exercise therapy, intra-articular drug injection, and physiotherapy. Among these treatments, radial extracorporeal shock wave therapy (rESWT) has recently attracted increasing attention (6). rESWT is widely used for pain relief and the treatment of musculoskeletal disorders, and has proven beneficial at specific stages of KOA (7).An extracorporeal shock wave is a transient sequence of acoustic pulses with a high peak pressure of 100 MPa, followed by a negative pressure of approximately 5–10 MPa, with an energy density between 0.003 and 0.89 mJ/mm² (8). Radial shock wave devices generate the maximum energy at the probe tip and then distribute it radially into the tissue, providing effective treatment (9). rESWT may be a more acceptable treatment for some patients because of its non-invasiveness, low complication rate, lack of required hospitalization and low cost compared with other approaches. However, rESWT has not met established efficacy standards, and the optimal dose is unknown. A meta-analysis indicated that the effects of rESWT are superior to those of a placebo and physical therapy for pain relief in KOA (10). Nevertheless, an RCT that applied a relatively small dose of radial extracorporeal shock waves did not demonstrate any statistically significant difference from a placebo treatment in terms of pain control in patients with severe KOA (11). Another systematic review identified that the positive energy flux density (EFD) should be as high as possible; however, the dose was based on the subjective feeling of the individual patient (12).It is important to quantify the amount of rESWT needed to reduce symptoms of KOA and establish the efficacy of rESWT. Thus, the primary aim of this prospective randomized placebo-controlled study was to test whether there was a dose-response relationship between the treatment doses and reduction in pain and dysfunction. The secondary aim was to examine whether the mean change in pain and function scores was greater for the active rESWT conditions than for the placebo control 4 weeks after the final treatment.     

IgE and IgG Anti-Thyroid Autoantibodies in Chinese Patients With Chronic Spontaneous Urticaria and a Literature Review

Immunoglobulin (Ig) E and IgG anti-thyroid autoantibodies (AAbs) play important roles in the immunopathogenesis of chronic spontaneous urticaria (CSU). To date, association of IgE and IgG AAbs with Chinese CSU patients has not been fully investigated. We aimed to explore prevalence rates of IgE and IgG AAbs in Chinese CSU patients and their association with clinical and laboratory parameters. Serum IgE and IgG AAbs against thyroid peroxidase (TPO) and thyroglobulin (TG), total IgE (tIgE) and specific IgEs were measured using enzyme-linked immunosorbent assay, chemiluminescence microparticle immunoassay and immunoblotting. Meta-analyses and literature review were conducted. The meta-analyses indicated that CSU cases were 4.98, 6.90 and 6.68 times more likely to have positive anti-TPO IgE, anti-TPO IgG and anti-TG IgG (all P < 0.001) compared with controls, respectively, and revealed a positive correlation between the prevalence rates of anti-TPO IgE and anti-TPO IgG (r = 0.53, P = 0.025). A total of 1,100 Chinese Han adult CSU patients and 1,100 ethnicity-, age- and sex-matched healthy controls were recruited from 15 centers. Prevalence rates of anti-TPO IgE, anti-TPO IgG, anti-TG IgE or anti-TG IgG in the patients were all significantly higher than those in the controls. Significant correlations were observed between prevalence rates of anti-TPO IgE and anti-TPO IgG (r = 0.297, P < 0.001) as well as between those of anti-TG IgE and anti-TG IgG in the patients (r = 0.137, P < 0.001). Patients with anti-TPO IgE or anti-TPO IgG had significantly lower tIgE levels (P < 0.001). Positive anti-TPO IgE, positive anti-TPO IgG and tIgE < 40 IU/mL were independent predictors of antihistamine-refractory cases. In conclusion, the prevalence rates of IgE and IgG AAbs in Chinese CSU patients are significantly elevated and reciprocally correlated. This study verifies the results of previous case-control studies of CSU patients from other populations and ethnicities.     

Guidelines for the diagnosis and treatment of acute pancreatitis in China (2021)

Acute pancreatitis (AP) is a common acute abdominal condition of the digestive system. In recent years, treatment concepts, methods, and strategies for the diag...     

河南省三株人源隐孢子虫分离株鉴定

目的隐孢子虫病是一种人兽共患寄生虫病,在艾滋病病人和儿童中的感染率可分别高达48％和17．5％,可导致严重的水样腹泻甚至危及生命,免疫功能正常者也能感染出现急性自限性腹泻。本文通过不同软件对三株人源隐孢子虫分离株进行种类鉴定。方法参照Xiao L H 1999年发表的资料合成隐孢子虫18S rDNA特异性引物(上游引物:5’-AACCTGGTTGATCCTGCCAGTAGTC -3’,下游引物:5’-TGAGCCTTCTGCAGGTTCACCTACG-3’,由大连宝生物工程技术公司合成。),FCR 扩增,产物测序、序列分别用Paup4．0、rhylip3．6、DNAstar4．0等软件分析并与12株隐孢子虫相应序列进行同源性分析,绘制了系统发育进化树,分析鉴定。1、2号株采自非免疫抑制病人,3号株采自免疫抑制病人。结果①三株隐孢子虫均能扩增出1700bp左右的目的片段。②构建系统发生树;用DNAstar4．0软件进行分析:1与2号株的同源性为99．8％,1和2号株与 AF108864 C．parvum-cattle的同源性分别为99．5％和99．3％,与AF112569 C．hominis进化关系较远。3号株与AF112574 C． meleagridis(火鸡源 C．meleagridis)的同源性为99．8％,3号株与C．suis(AF108861)的同源性为98．9％,而与AF108864 C．parvum -cattle、AF112569 C．hominis、AF108865 C．parvum(Homo sapiens)、AY642591 C．muris、AB210854 C．canis、AF108862 C． felis等均不处于同一进化枝,亲缘关系较远。利用PAUP4．0、Phylip3.6的方法与DNAstar4．0 软件分析的结果基本一致。结论 1和2号分离株均为C．parvum牛基因型,3号分离株是C．meleagridis(火鸡隐孢子虫)。本文结果为深入研究人隐孢子虫病的分子流行病学打下基础。     

橙皮苷及其衍生物抗癌作用机制的研究进展

该文通过检索中国知网、万方、PubMed等电子数据库,回顾过去10年发表的关于橙皮苷预防及治疗癌症的相关文献,总结了橙皮苷抗癌机制的研究进展。橙皮苷的药理作用十分广泛,具有抗炎、抗氧化、抗菌、抗病毒、抗癌、调节免疫力、抗辐射、神经保护、心血管保护等作用。其抗癌机制主要包括抑制癌细胞增殖、促进癌细胞凋亡、减少血管生成、抑制癌细胞侵袭和迁移、调节免疫与自噬、抗炎抗氧化。这种多方面的抗癌机制使橙皮苷对多种癌症显示出化学预防和治疗效果,使其成为一种广谱抗癌药。该文还总结了橙皮苷与顺铂、阿霉素、环磷酰胺、紫杉醇4种抗癌药合用的效果,发现橙皮苷能增强这些抗癌药对癌细胞的增殖抑制作用,还能降低耐药性和不良反应。由于橙皮苷水溶性较差,生物利用度不高,临床使用受到一定限制,因此还总结了目前通过结构修饰或与其他化学物质、纳米载药制剂组合获得的衍生物来提高其生物利用度的方法。发现橙皮苷的衍生物既保留了橙皮苷的抗癌疗效,又有效克服了橙皮苷水溶性差、生物利用率低等缺陷,很好地预测了橙皮苷及其衍生物具备的良好应用前景。     

颈动脉粥样硬化性狭窄治疗研究进展

目前,我国脑缺血性卒中的致死率和致残率位居 所有疾病首位[1] 。研究[2] 发现,在缺血性脑卒中和短暂 性 脑 缺 血 发 作（transient ischemic attack,TIA）的 患 者中有 20％的患者存在颈动脉狭窄。颈动脉狭窄最 常见的病因是颈动脉粥样硬化[3] ,且颈动脉粥样硬化 性狭窄的发病率随着年龄增大而增加,且男性高于女 性[4] 。在以大动脉粥样硬化为病因的缺血性脑血管病 中,颈内动脉粥样硬化性狭窄所占比例最大[5] ,大动脉 粥样硬化导致的TIA患者在早期复发缺血性卒中的风 险会增加 1倍[6] ,且TIA或轻型缺血性卒中伴有动脉粥 样硬化的患者,在未来 5年内发生大血管事件的风险 远高于不伴有动脉粥样硬化患者[7] 。     

Antipsychotics Effects on Network-Level Reconfiguration of Cortical Morphometry in First-Episode Schizophrenia

Cortical thickness reductions are evident in schizophrenia (SZ). Associations between antipsychotic medications (APMs) and cortical morphometry have been explored in SZ patients. This raises the question of whether the reconfiguration of morphological architecture by APM plays potential compensatory roles for abnormalities in the cerebral cortex. Structural magnetic resonance imaging was obtained from 127 medication-naive first-episode SZ patients and 133 matched healthy controls. Patients received 12 weeks of APM and were categorized as responders (n = 75) or nonresponders (NRs, n = 52) at follow-up. Using surface-based morphometry and structural covariance (SC) analysis, this study investigated the short-term effects of antipsychotics on cortical thickness and cortico-cortical covariance. Global efficiency was computed to characterize network integration of the large-scale structural connectome. The relationship between covariance and cortical thinning was examined by SC analysis among the top-n regions with thickness reduction. Widespread cortical thickness reductions were observed in pre-APM patients. Post-APM patients showed more reductions in cortical thickness, even in the frontotemporal regions without baseline reductions. Covariance analysis revealed strong cortico-cortical covariance and higher network integration in responders than in NRs. For the NRs, some of the prefrontal and temporal nodes were not covariant between the top-n regions with cortical thickness reduction. Antipsychotic effects are not restricted to a single brain region but rather exhibit a network-level covariance pattern. Neuroimaging connectomics highlights the positive effects of antipsychotics on the reconfiguration of brain architecture, suggesting that abnormalities in regional morphology may be compensated by increasing interregional covariance when symptoms are controlled by antipsychotics.