Neuroprotective strategies in parkinson’s disease: protection against progressive nigral damage induced by free radicals

Brain undergoes neurodegeneration when excess free radicals overwhelm antioxidative defense systems during senescence, head trauma and/or neurotoxic insults. A site-specific accumulation of ferrous citrate-iron complexes in the substantia nigra dopaminergic neurons could lead to exaggerated dopamine turnover, dopamine auto-oxidation, free radical generation, and oxidant stress. Eventually, this iron-catalyzed dopamine auto-oxidation results in the accumulation of neuromelanin, a progressive loss of nigral neurons, and the development of Parkinson's disease when brain dopamine depletion is greater than 80%. Emerging evidence indicates that free radicals such as hydroxyl radicals ((.-)OH) and nitric oxide ((.-)NO) may play opposite role in cell and animal models of parkinsonism. (.-)OH is a cytotoxic oxidant whereas oNO is an atypical neuroprotective antioxidant. (.-)NO and S-nitrosoglutathione (GSNO) protect nigral neurons against oxidative stress caused by 1-methyl-4-phenylpyridinium (MPP(+)), dopamine, ferrous citrate, hemoglobin, sodium nitroprusside and peroxynitrite. MPP(+), the toxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), increases the nigral uptake of iron complexes and dopamine overflow leading to the generation of (.-)OH, protein oxidation, lipid peroxidation, and associated retrograde degeneration. In addition to GSNO, MPP(+)-induced oxidative neurotoxicity can be prevented by antioxidants including selegiline, 7-nitroindazole, 17beta-estradiol, melatonin, alpha-phenyl-tert-butylnitrone and U78517F. Similar to selegiline, 7-nitroindazole is a MAO-B inhibitor, which blocks the bio-activation of MPTP and oxidative stress. Freshly prepared but not light exposed, (.-)NO-exhausted GSNO is about 100 times more potent than the classic antioxidant glutathione. Via S-nitrosylation, GSNO also inhibits proteolysis and cytotoxicity caused by caspases and HIV-1 protease. Furthermore, in addition to protection against serum deprivation stress, the induction of neuronal NOS1 in human cells increases tolerance to MPP(+)-induced neuro-toxicity since newly synthesized (.-)NO prevents apoptosis possibly through up-regulation of bcl-2 and down regulation of p66(shc). In conclusion, reactive oxygen species are unavoidable by-products of iron-catalyzed dopamine auto-oxidation, which can initiate lipid peroxidation, protein oxidation, DNA damage, and nigral loss, all of which can be prevented by endogenous and exogenous (.-)NO. Natural and man-made antioxidants can be employed as part of preventative or neuroprotective treatments in Parkinson's disease and perhaps dementia complexes as well. For achieving neuroprotection and neuro-rescue in early clinical parkinsonian stages, a cocktail therapy of multiple neuroprotective agents may be more effective than the current treatment with extremely high doses of a single antioxidative agent.     

7,7'-Dimethoxyagastisflavone-induced apoptotic or autophagic cell death in different cancer cells

7,7'-Dimethoxyagastisflavone (DMGF), a biflavonoid isolated from the needles of Taxus × media cv. Hicksii, was evaluated for its antiproliferative and antineoplastic effects in three human cancer cell lines. Interestingly, DMGF caused cell death via different pathways in different cancer cells. DMGF induced apoptosis, activated caspase-3 activity and changed the mitochondrial membrane potential in HT-29 human colon cancer cells. However, the apoptotic pathway is not the major pathway involved in DMGF-induced cell death in A549 human lung cancer cells and HepG2 human hepatoma cells. Treatment with 3-MA, an inhibitor of autophagy, significantly decreased DMGF-induced cell death in HepG2 and A549 cells, but did not affect DMGF-induced cell death in HT-29 cells. Following DMGF treatment, the HepG2 cells increased expression of LC3B-II, a marker used to monitor autophagy in cells. Thus, DMGF induced apoptotic cell death in HT-29 cells, triggered both apoptotic and autophagic death in A549 cells and induced autophagic cell death in HepG2 cells.     

Photodynamic Therapy in Macular Diseases of Asian Populations: When East Meets West

Purpose

We reviewed the indications, safety, and efficacy of photodynamic therapy with verteporfin in various macular diseases and vasculopathies, which are common in Asian populations, and compared the outcomes of photodynamic therapy in Asian patients with the outcomes in Caucasian patients.

Methods

Relevant clinical and laboratory original articles, case reports, and review articles that have been published in the literature between January 1999 and October 2004 were searched in Medline. The potential differences in the response to photodynamic therapy between Asian and Caucasian patients were evaluated. Articles in foreign languages with English abstracts were included.

Results

Macular diseases commonly seen in Asian populations, including choroidal neovascularization (CNV) of age-related macular degeneration, secondary to pathologic myopia or from an idiopathic cause, and choroidal vasculopathies such as central serous chorioretinopathy and polypoidal choroidal vasculopathy were included in the review. The results were tabulated and the differences with Caucasian populations were compared and highlighted.

Conclusion

Photodynamic therapy has been found to be an effective and noninvasive treatment for various subfoveal CNV and choroidal vasculopathies of the macula. Diverse behavior in different ethnic groups is observed. Jpn J Ophthalmol 2006;50:161–169 © Japanese Ophthalmological Society 2006     

生脉注射液在气管插管后血压降低中的运用

生脉注射液具有益气养阴、复脉固脱之功效,广泛用于严重感染、血容量不足引起的血压降低.在气管插管后血压降低时,应用生脉注射液也取得了较好的临床疗效.本文对气管插管后血压降低应用生脉注射液的用法用量、注意事项等进行了归纳.     

普济宣肺消毒饮治疗急性支气管炎化痰作用临床观察

目的 观察普济宣肺消毒饮对急性支气管炎化痰作用.方法 用随机、对照、前瞻性研究方法,将87例急性支气管炎（表寒里热证）患者随机分为治疗组44例和对照组43例,治疗组服用普济宣肺消毒饮,对照组用急支糖浆治疗,观察对咯痰的影响,疗程为7d.结果 治疗组对咯痰、发热、头痛、恶风等症状有明显治疗作用,治疗后咯痰疗效和评分低于对照组,化痰疗效优于对照组（P＜0.05）.结论 普济宣肺消毒饮有一定的化痰作用.     

Prevalence and risk factors for postinfectious cough in discharged patients with coronavirus disease 2019 (COVID-19)

BackgroundCough is one of the most common symptoms of coronavirus disease 2019 (COVID-19). However, the prevalence of persistent cough in recovered patients with COVID-19 during a longer follow-up remained unknown. This study aims to investigate the prevalence, and risk factors for postinfectious cough in COVID-19 patients after discharge.MethodsWe conducted a follow-up study for 129 discharged patients with laboratory-confirmed COVID-19 in two large hospitals located in Hubei Province, China from January 2020 to December 2020. Baseline demographics, comorbidities and smoking history were extracted from the medical record. Current symptoms and severity were recorded by a uniform questionnaire. Spirometry, diffuse function and chest computed tomography (CT) were performed on part of patients who were able to return to the outpatient department at follow-up.ResultsThe median (interquartile range) follow-up time was 8.1 (7.9–8.5) months after discharge. The mean (standard deviation) age was 51.5 (14.9) years and 57 (44.2%) were male. A total of 27 (20.9%) patients had postinfectious cough (>3 weeks), 6 patients (4.7%) had persistent cough by the end of follow-up, including 3 patients with previous chronic respiratory diseases or current smoking. Other symptoms included dyspnea (6, 4.7%), sputum (4, 3.1%), fatigue (4, 3.1%), and anorexia (4, 3.1%) by the end of follow-up. Thirty-six of 41 (87.8%) patients showed impaired lung function or diffuse function, and 39 of 50 (78.0%) patients showed abnormal CT imaging. Patients with postinfectious cough demonstrated more severe and more frequent cough during hospitalization (P<0.001), and more chronic respiratory diseases (P=0.01). In multivariate logistic regression analysis, digestive symptoms during hospitalization [odds ratio (OR) 2.95, 95% confidence interval (CI): 1.10–7.92] and current smoking (OR 6.95, 95% CI: 1.46–33.14) were significantly associated with postinfectious cough of COVID-19.ConclusionsA small part of patients developed postinfectious cough after recovery from COVID-19, few patients developed chronic cough in spite of a higher proportion of impaired lung function and abnormal lung CT image. Current smoking and digestive symptoms during hospitalization were risk factors for postinfectious cough in COVID-19.     

Accelerated-strategy renal replacement therapy for critically ill patients: A systematic review and meta-analysis

Background:The aim of this study was to investigate the clinical effect and safety of accelerated-strategy initiation of renal replacement therapy (RRT) in critically ill patients.Methods:PubMed, Embase, OVID, EBSCO, and the Cochrane Library databases were searched for relevant articles from inception to December 30, 2020. Only RCTs that compared the clinical efficacy and safety between accelerated-strategy RRT and standard-strategy RRT among critically ill adult patients with acute kidney injury (AKI) were included. The primary outcome was 28-day mortality.Results:A total of 5279 patients in 12 RCTs were included in this meta-analysis. The 28-day mortality rates of patients treated with accelerated and standard RRT were 37.3% (969/2596) and 37.9% (976/2573), respectively. No significant difference was observed between the groups (OR, 0.92; 95% CI, 0.70–1.12; I² = 60%). The recovery rates of renal function were 54.5% and 52.5% in the accelerated- and standard-RRT groups, respectively, with no significant difference (OR, 1.03; 95% CI, 0.89–1.19; I² = 56%). The rate of RRT dependency was similar in the accelerated- and standard-RRT strategies (6.7% vs 5.0%; OR, 1.11; 95% CI, 0.71–1.72; I² = 20%). The accelerated-RRT group displayed higher risks of hypotension, catheter-related infection, and hypophosphatemia than the standard-RRT group (hypotension: OR, 1.26; 95% CI, 1.10–1.45; I² = 36%; catheter-related infection: OR, 1.90; 95% CI, 1.17–3.09; I² = 0%; hypophosphatemia: OR, 2.11; 95% CI, 1.43–3.15; I² = 67%).Conclusions:Accelerated RRT does not reduce the risk of death and does not improve the recovery of kidney function among critically ill patients with AKI. In contrast, an increased risk of adverse events was observed in patients receiving accelerated RRT. However, these findings were based on low quality of evidence. Further large-scale RCTs is warranted.     

听神经瘤误诊分析

对经耳鼻咽喉科首诊，最终由神经外科手术全切或部分切除的经病理证实的７２例听神经瘤进行早期误诊分析，误诊时间平均５．５年，误诊病种为神经性耳聋、突发性耳聋、神经性耳鸣、颈椎病、鼻咽癌等。文中重点讨论了误诊原因。     

腔内微波和射频消融闭合大隐静脉主干的疗效及安全性对比分析

目的 探讨血管腔内微波消融（EMA）与射频消融（RFA）闭合大隐静脉主干的疗效和安全性差异。方法 收集2019年1—6月浙江省人民医院收治的316例大隐静脉功能不全患者的临床资料,并按照性别、年龄、病程、体重指数、身高、基础临床表现-病因-解剖-病理生理（CEAP）分级、大隐静脉主干直径的不同将患者筛选并分层配对为EMA组（n=157）和RFA组（n=159）。采用视觉模拟评分法（VAS）评价两组患者术后14 d的大隐静脉主干闭合段疼痛情况和皮肤瘀伤情况;术后第14天、6个月,所有患者均通过超声复查治疗段大隐静脉主干闭合情况。比较两组患者的术后并发症发生情况。结果 RFA组患者的术后VAS最高评分出现在术后第1天,EMA组患者的术后VAS最高评分出现在术后第3天。术后第1～10天,两组患者的VAS评分存在差异;与EMA组患者相比,RFA组患者的术后VAS评分更低。两组患者的皮肤瘀伤最高评分均出现在术后第4天;与EMA组患者相比,RFA组患者的皮肤瘀伤评分较低;术后第5～9天,两组患者的皮肤瘀伤评分差异较大。两组患者术后第14天、6个月的治疗段大隐静脉主干闭合率、术后并发症发生情况比较,...