Blood glucose changes surrounding initiation of tumor-necrosis factor inhibitors and conventional disease-modifying anti-rheumatic drugs in veterans with rheumatoid arthritis

AIM To determine the scope of acute hypoglycemic effects for certain anti-rheumatic medications in a large retrospective observational study. METHODS Patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry were selected who, during follow-up, initiated treatment with tumor necrosis factor inhibitors (TNFi's, including etanercept, adalimumab, infliximab, golimumab, or certolizumab), prednisone, or conventional disease-modifying anti-rheumatic drugs(DMARDs), and for whom proximate random blood glucose (RBG) measurements were available within a window 2-wk prior to, and 6 mo following, medication initiation. Similar data were obtained for patients with proximate values available for glycosylated hemoglobin A1C values within a window 2 mo preceding, and 12 mo following, medication initiation. RBG and A1C measurements were compared before and after initiation events using paired t-tests, and multivariate regression analysis was performed including established comorbidities and demographics.RESULTS Two thousands one hundred and eleven patients contributed at least one proximate measurement surrounding the initiation of any examined medication. A significant decrease in RBG was noted surrounding 653 individual hydroxychloroquine-initiation events(-3.68 mg/dL, P = 0.04), while an increase was noted for RBG surrounding 665 prednisone-initiation events(+5.85 mg/d L, P < 0.01). A statistically significant decrease in A1C was noted for sulfasalazine initiation, as measured by 49 individual initiation events(-0.70%, P < 0.01). Multivariate regression analyses, using methotrexate as the referent, suggest sulfasalazine (β =-0.58, P = 0.01) and hydroxychloroquine(β =-5.78, P = 0.01) use as predictors of lower post-medicationinitiation RBG and A1C values, respectively. Analysis by drug class suggested prednisone (or glucocorticoids) as predictive of higher medication-initiation event RBG among all start events as compared to DMARDs, while this analysis did not show any drug class-level effect for TNFi. A diagnosis of congestive heart failure(β = 4.69, P = 0.03) was predictive for higher post-initiation RBG values among all medication-initiation events.CONCLUSION No statistically significant hypoglycemic effects surrounding TNFi initiation were observed in this large cohort. Sulfasalazine and hydroxychloroquine may have epidemiologically significant acute hypoglycemic effects.

An investigation into the occupational protection status of clinical nursing staff exposed to anti-tumor drugs

Objective:To investigate the occupational protection status of clinical nursing staff vocationally exposed to anti-tumor drugs.Methods:A self-designed questionnaire was used to survey 180 clinical nursing staff vocationally exposed to anti-tumor drugs.Results:Recognition of the need for protection and dependent occupational protection behaviors were very poor in clinical nursing staff vocationally exposed to anti-tumor drugs.The management of the occupational protection of clinical nursing staff vocationally exposed to anti-tumor drugs was also seriously underdeveloped.Conclusion:There is deficiency in the understanding and related protection practices of clinical nursing staff vocationally exposed to anti-tumor drugs in our hospital.The protection measures currently employed in medical practice are inadequate in virtually every aspect considered.It is recommended that all clinical nursing staff should receive full occupational protection training in these matters.The training must raise nursing staff's awareness of the need for occupational protection and standardize their occupational protection behaviors to conform to "best practice" models.These "best practice" models should be quickly established and all staff made cognizant of them forthwith.In addition,where occupational protection systems are already in place,they should be improved to come into line with the new "best practice" models instigated.

Adverse Drug Reactions in Patients on Second Line Anti-Tubercular Drugs for Drug Resistant Tuberculosis in Rural Tertiary Care Hospital in North India

Introduction: The adverse drug events (ADEs) to second-line anti-TB drugs are one of the major reasons for the patients default on treatment. A general awareness of various adverse drug events (ADE) and their management is essential for the effective management of tuberculosis. Identification of adverse drug reaction profile of patients can be useful for the early detection, management and prevention of adverse drug events. Material and methods: It was a prospective observational study conducted after approved Institutional Ethics Committee. A total of 104 drug resistant tuberculosis patients registered from 1st November 2012 to 31st October 2013 started with second line anti-tubercular drugs under PMDT-RNCP after taking written informed consent. Adverse drug reaction during treatment recorded and assessed by Hart wig and WHO scale. Results: 87% patients experienced adverse drug reactions. Total 346 ADR were reported. Most common were gastritis (65%) and arthralgia (60.6%), others were nausea (35.6%), vomiting (32.7%), hyperuricemia (30.8%), giddiness (27%), anorexia (17.3), generalized weakness (15.4), insomnia (10.6%), psychosis (8.6%), hearing impairment (6.7%), hypersensitivity reaction (5.8%), peripheral neuropathy (4.8%), visual disturbance (3.8%), nephrotoxicity (2.9%), forgetfulness (2.9%), gynaecomastia (1.9%), hypothyroidism (1%), seizure (1%), and thrombocytopenia (1%). Conclusion: Majority of patients experienced wide range adverse drug reactions. Most of patients faced the problem within 2 - 3 months of initiation of treatment and managed by symptomatic. Early identification, prompt management and standardized reporting adverse drug reactions at all the level of healthcare are needed.

Strategies for overcoming anti-tumor necrosis factor drug antibodies in inflammatory bowel disease:Case series and review of literature

Anti-tumor necrosis factor(TNF) biologics are currentlyamongst the most widely used and efficacious therapies for inflammatory bowel disease(IBD). The development of therapeutic drug monitoring for infliximab and ada-limumab has allowed for measurement of drug levels and antidrug antibodies. This information can allow for manipulation of drug therapy and prediction of response. It has been shown that therapeutic anti-TNF drug levels are associated with maintenance of remission, and development of antidrug antibodies is predictive of loss of response. Studies suggest that a low level of drug antibodies, however, can at times be overcome by dose escalation of anti-TNF therapy or addition of an immunomodulator. We describe a retrospective case series of twelve IBD patients treated at the University of California-Irvine, who were on infliximab or adalimumab therapy and were found to have detectable but low-level antidrug antibodies. These patients underwent dose escalation of the drug or addition of an immunomodulator, with subsequent follow-up drug levels obtained. Eight of the twelve patients(75%) demonstrated resolution of antidrug antibodies, and were noted to have improvement in disease activity. Though data regarding overcoming low-level anti-TNF drug antibodies remains somewhat limited, cases described in the literature as well as our own experience suggest that this may be a viable strategy for preserving the use of an anti-TNF drug. Low-level anti-TNF drug antibodies may be overcome by dose escalation and/or addition of an immunomodulator, and can allow for clinical improvement in disease status. Therapeutic drug monitoring is an important tool to guide this strategy.

First Line Anti-Tuberculosis Drugs Resistance Patterns of <i>Mycobacterium tuberculosis</i>Isolates from Newly Diagnosed Cases of Tuberculosis

Introduction: Tuberculosis is a major cause of mortality and morbidity world-wide. Anti-tuberculosis drugs have been used for many decades but resistance to them is now widespread. Globally 5% of tuberculosis cases and in India 3% among new TB cases. This study was planned to know the pattern of first line anti-tuberculosis drug resistance in south Gujarat, Surat region in newly diagnosed patients of tuberculosis. Material and Methods: 350 samples were processed for homogenisation and concentration using 4% NAOH-2.9% trisodium citrate. Processed samples were inoculated in liquid medium that is MGIT (Mycobacterial growth indicator tube). Positive samples for M. tbwere processed further for first line anti-tuberculosis drugs sensitivity testing (DST). Reading was taken by using MicroMGIT system. Result: Out of 350 samples 59 (17%) were positive samples, of which 48 (13%) were M. tb and 11 (3%) were non tuberculous mycobacteria. Out of 48 samples 2% (1 isolate) was resistant to isoniazid and Rifampicin while 2% were monoresistant to isoniazide, 2% monoresistant to streptomycin. No rifampicin monoresistant was detected. Conclusion: Such study may help in control of tuberculosis at regional and national level which would in turn help in planning of measures to control Multi-drug resistance tuberculosis. Continuous surveillance should be applied to know the periodic changing patterns and trend in Drug resistant tuberculosis.

Use of Cost Effective Semi-Automated (Mannual/Micro) MGIT System over BACTEC 960 to Perform First Line Anti-Tuberculosis Drugs Sensitivity Testing

Introduction: Multi-drug resistant tuberculosis (MDR-TB) that is the tuberculosis that is resistant to at least 2 of the first line anti-tuberculosis drugs is fatal infectious disease. Cases of MDR-TB are now increasing with 30,000 cases of MDR-TB reported in 2013 by national TB programme. Rapid diagnosis of MDR-TB is extremely important for rapid treatment of patient and to prevent spread of MDR-TB to other. BACTEC 960 system helps in rapid diagnosis but purchase of expensive instrument for the same is the limitation. However, the same purpose can be solved by use of semi-automated MGIT system. Aims and Objectives: Aim of this study is to do drug sensitivity testing of the first line anti-tuberculosis drugs with the use of semi-automated MGIT systems. 350 newly registered and suspected cases of tuberculosis in tertiary care hospital were included. Samples were processed for digestion and decontamination and inoculated in MGIT tubes and also on LJ medium. Reading was taken using semi-automated MGIT system. Positive tubes were confirmed by rapid test for M. tuberculosis and then drug sensitivity was performed. Result: Out of 350 samples, 62% were sputum;33% were pleural fluid and rest 5% were lymph node, Ascetic fluid, CSF, pus. Average day of positivity by MGIT was 13 - 20 days as compared to 25 - 37 days by solid medium, which was statistically significant with p value Conclusion: Manual MGIT System is a simple, efficient, safe to use diagnostic system. It does not require any expensive/special instrumentation other than the UV lamp for detection of fluorescence. The rapidity by which mycobacteria are detected is the most important advantage of the Manual MGIT. In areas with limited resources where purchase of expensive instruments such as the MGIT960 is out of scope, the use of manual MGIT for rapid susceptibility testing for MDR-TB could be a possibility.

Autoimmune hepatitis and anti-tumor necrosis factor alpha therapy:A single center report of 8 cases

This article describes cases of anti-tumor necrosis factor(TNF)-α-induced autoimmune hepatitis and evaluates the outcome of these patients in relation to their immunosuppressive strategy. A retrospective analysis of medical records was performed in our center, in order to detect cases of autoimmune hepatitis(AIH) associated with anti-TNF biologic agents. We describe and analyze eight cases of AIH following anti-TNF therapy, 7 with infliximab and 1 with adalimumab. A distinction should be made between induction of autoimmunity and clinically evident autoimmune disease. Liver biopsy is useful in detecting the role of the TNF-α antagonist in the development of AIH. The lack of relapse after discontinuing immunosuppressive therapy favors, as in this case series, an immune-mediated drug reaction as most patients with AIH have a relapse after treatment is suspended. Although AIH related to anti-TNF therapy is rare, a baseline immunological panel along with liver function tests should be performed in all patients with autoimmune disease before starting biologics.

EFFECT OF ASCORBIC ACID ON DNA SYNTHESIS,INTRACELLULAR ACCUMULATION OF ADM AND ADM RESISTANCE OF TUMOR CELL LINES

Objective: To determine the effect of ascorbic acid (AA) on DNA synthesis, intracellular accumulation of ADM and ADM resistance of tumor cell lines. Methods: K562, K562/ADM and KB cell lines were used to study the effect of ascorbic acid on DNA synthesis, intracellular accumulation of ADM and ADM resistance by fluid scintillometry, MTT method, spectrofluorophotometry and immunocytochemistry. Results: Results showed that AA was capable of inhibiting DNA synthesis of K562 and K562/ADM in a dosedependence fashion, but not KB cell line, and significantly reducing ADM sensitivity in K562 and KB cell lines, as well as potentiating obviously ADM resistance in K562/ADM cell line. Conclusion: These effects of AA may be closely correlated with significant elevation of intracellular accumulation of ADM in KB cell line, and significant reduction of that in K562 and K562/ADM cell lines but possibly not correlated with the expression of Pglycoprotein.

Overview of Research and Development for Anticancer Drugs

Anticancer drugs research and development have been the largest market area in the pharmaceutical industry in terms of the number of project, clinical trials and spending. In the last 10 - 30 years, targeting therapy for cancers has been developed and achieved enormous clinical effectiveness by transforming some previously deadly malignancies into chronically manageable conditions, but cure problem still remains. This mini review outlined the current status of anticancer drugs development and hinted the opinions of how to further increase the accuracy and efficacy of discovery for cancer treatment.

纳米金材料在肿瘤诊治领域中的应用研究进展

在肿瘤的预防与控制方面,实施“三早”策略——即早期发现、早期诊断、早期治疗——被认为是实现一级预防效果的最有效途径。尽管如此,当前肿瘤早期诊断的技术和能力仍然遭遇着重大挑战。另一方面,传统的抗肿瘤药物由于其高毒性和缺乏针对特定组织的特异性,导致在实际治疗中的应用受到了显著限制。纳米金材料因其独特的优势而脱颖而出,包括表面易于改性、出色的生物相容性、小尺寸带来的特殊效应、光学性质以及量子效应等,使其在肿瘤细胞的诊断和治疗方面显示出巨大的应用潜力。近年来,纳米金在肿瘤的临床诊断和治疗领域受到了广泛的关注和研究,并已取得了令人鼓舞的进展。该文旨在对纳米金材料在肿瘤诊治领域中的最新研究进展进行全面的综述,以期为肿瘤患者提供更加有效和个性化的诊疗方案,推动其在临床实践中的广泛应用。

基于高通量表面等离子体共振技术筛选与TPBG具有高亲和力的单克隆抗体研究

目的探讨从制备的单克隆抗体中快速筛选出与滋养层糖蛋白(TPBG)具有高亲和力的单克隆抗体的方法。方法采用高通量表面等离子体共振技术(SPR),将不同种属的TPBG通过氨基偶联的方式固定在GLC传感器芯片上,梯度稀释的抗体作为流通相,筛选能高度亲和TPBG的单克隆抗体,并测定相互作用的动力学常数。抗体1结合人和食蟹猴TPBG,亲和力分别为65.0、31.6 nmol/L;抗体6结合人、小鼠、食蟹猴TPBG,亲和力分别为77.6、92.1、87.7 nmol/L。结果该研究成功筛选出2种能与TPBG特异性结合的单克隆抗体。动力学图谱显示,这2种抗体与TPBG蛋白的特异性结合稳定。结论采用SPR可筛选出与TPBG蛋白具有高亲和力的单克隆抗体,为开发出一些新型的抗肿瘤药物提供一种方法。

抗肿瘤药审方规则的设置优化及实施效果评价

目的探讨抗肿瘤药审方规则设置及优化流程,提高处方合理率,降低不合理处方退费率。方法统计抗肿瘤药规则设置优化前(2021年12月~2022年3月)规则维护后(2022年4月~2022年7月)的门诊处方。比较规则设置优化前后处方合理率及退费率评价实施效果。结果设置了抗肿瘤药规则,建立了规则优化模式,形成了超说明书用药规则库。门诊处方合理率由96.53%提高到99.19%(P<0.001),处方退费率由1.11%降至0.23%(P<0.001),差异有统计学意义。结论我院维护的抗肿瘤药审方规则库提高了处方合理率,保障临床用药的同时提高了患者用药安全性及合理性。

晚期胃癌内科治疗十年研究回顾与现状

目前胃癌是我国发病率和死亡率分别居于第5位和第3位的恶性肿瘤,给居民生命健康和我国卫生经济带来巨大负担。由于胃癌的早期筛查仍未全面普及,我国近一半的胃癌患者发现时已是晚期,预后不良。近年来,随着抗肿瘤新药临床研究的不断推进,新型药物的研发和上市给晚期胃癌患者带来了新的治疗机会。本文汇总近10年晚期胃癌领域新药临床研究,从靶向治疗、免疫治疗、抗血管生成治疗和新型化疗药物等不同角度,分析和阐述晚期胃癌内科治疗中的临床研究进展,并对未来研究进行展望,以在此基础上期待开展更加高质量的临床研究,更进一步改善晚期胃癌患者的生存和预后。

刺激响应型纳米载药系统用于抗多药耐药肿瘤的研究进展

目的 对新型刺激响应型纳米载药系统(nanodrug delivery systems, NDDS)在抗肿瘤多药耐药(multidrug resistance, MDR)中的应用进行综述。方法 通过查阅近年来国内外相关文献,对各种新型刺激响应型纳米载药系统在抗MDR型肿瘤方面的研究进展进行整理归纳。结果 目前已有多种内源性和外源性刺激响应型及多重响应型纳米载药系统构建成功并应用于抗MDR型肿瘤,取得了良好的疗效。结论 纳米载体具有生物相容性好,可修饰性强,载药量高等优点被广泛用于抗肿瘤药物递送领域。基于正常组织和肿瘤组织微环境的不同生理特性,合理设计开发新型刺激响应型纳米载药系统,可进一步提高药物递送的特异性和有效性,显著提升抗MDR型肿瘤的疗效。为后续的研究和开发提供有益参考。

去甲斑蝥素抗肿瘤作用机制与联合治疗潜力

目的 对去甲斑蝥素的药理作用机制及临床联用进行系统阐述,并对开发去甲斑蝥素新型给药系统进行展望,为去甲斑蝥素进一步深入研究和临床应用奠定基础。方法 查阅国内外相关文献,对去甲斑蝥素的药理作用机制和临床联合用药情况进行分析和归纳总结。结果 去甲斑蝥素既可以通过单药多靶点机制实现抗肿瘤作用,还具有升高白细胞和调节机体免疫平衡的功能;去甲斑蝥素在临床上可以与化疗药物、免疫药物、靶向药物或放射疗法等联用,实现协同抗癌作用;去甲斑蝥素有望开发出脂肪乳注射液、乳化体和脂质体-乳剂复合体等高靶向、缓控释、低毒性和不良反应少的新型改良系统。结论 去甲斑蝥素临床联用具有广阔的应用前景,有待进一步深入研究。

中药联合抗肿瘤血管生成药物治疗非小细胞肺癌的研究进展

非小细胞肺癌(NSCLC)是肺癌最为常见的一种病理类型,一半以上的患者确诊时即为进展期肺癌,患者生存期较短。抗肿瘤血管生成药物是目前治疗非小细胞肺癌的重要靶向药物,其临床疗效已获得临床认可,但仍存在耐药性及毒副作用不可耐受的局限性,而中药辨证论治及减毒增效的优点,可减轻药物的不良反应,并提高临床疗效,已成为中西医结合治疗非小细胞肺癌的重要方向。本文主要通过检索2010年1月—2023年6月中国知网、万方、维普及PubMed等数据库中的相关文献,总结近年来不同中药联合各类抗肿瘤血管生成药物治疗NSCLC的相关研究,试从不同角度探讨治疗NSCLC的新思路。

PD-1/PD-L1抑制剂在转移性结直肠癌中的应用研究进展

结直肠癌是目前全球常见恶性肿瘤之一,近年来其发病率和死亡率逐年上升。由于早期结直肠癌具有症状隐匿的特点,多数患者初诊时已发展为中晚期。对于IV期的转移性结直肠癌(mCRC),手术辅以放化疗治疗mCRC患者的5年生存率较低。随着近年来免疫学的发展,程序性死亡受体1(PD-1)/程序性死亡受体-配体1(PD-L1)抑制剂已在多种恶性肿瘤的治疗中取得突破性进展,能提高部分mCRC患者尤其是错配修复缺陷/微卫星高度不稳定型患者的疗效,并获得指南的推荐;但对于临床上占比达90%以上的错配修复完整/微卫星稳定型mCRC患者,应用PD-1/PD-L1抑制剂治疗效果差,但也有不同临床研究报道了部分该类型的mCRC能获得一定的受益。该文围绕PD-1/PD-L1抑制剂的抗肿瘤机制以及不同类型mCRC患者的PD-1/PD-L1抑制剂临床应用进展和研究现状作一综述,探究PD-1/PD-L1抑制剂联合治疗的可行性,以期为错配修复完整/微卫星稳定型患者获益和优化PD-1/PD-L1抑制剂在mCRC治疗中的用药方案提供参考。

新型抗肿瘤药物致神经系统疾病综述及风险信息管理

随着越来越多的新型抗肿瘤药物获批上市,对这些药物的临床安全性监测和风险信息管理成为迫切需要。药源性神经系统疾病存在起病隐匿﹑进展迅速和治疗棘手等特点,最终可能导致治疗失败。因此,充分了解新型抗肿瘤药物所致神经系统疾病的风险,并进行监护和预警,及时处理和上报,可大幅降低药源性疾病的发生和危害程度。本文对新型抗肿瘤药物所致神经系统疾病展开综述,介绍了此类药物临床使用的警戒体系和风险信息管理手段,以期为指导临床合理用药、减少药源性疾病的发生提供借鉴。

姜黄素与抗肿瘤药物联合应用的研究进展

联合用药能显著弥补单药使用的不足并能加快开发治疗复杂性疾病的新治疗方案.姜黄素是一种1,3-二酮类化合物,具有多种药理活性,其中抗肿瘤作用得到广泛关注.姜黄素能够抑制肿瘤细胞增殖、诱导肿瘤细胞凋亡等,具有毒性低、耐受性好等特点.研究发现:姜黄素与临床抗肿瘤药物联合应用具有一定的协同作用,能有效地抑制癌细胞生长,降低药物的毒副作用,减少药物剂量,达到增效减毒的效果.本文在细胞和实验动物水平上总结了姜黄素与抗肿瘤药物联合应用所产生的影响及可能的作用机制.

靶向表皮生长因子受体的百秋李醇纳米颗粒抑制非小细胞肺癌裸鼠皮下移植瘤生长的作用及机制

目的探讨靶向表皮生长因子受体(EGFR)的百秋李醇(PA)纳米颗粒对非小细胞肺癌(NSCLC)肿瘤生长的抑制作用及其机制。方法①利用二硬脂酰基磷脂酰乙醇胺-聚乙二醇-EGFR靶向肽AA1(DSPE-PEG-AA1)脂质体负载PA,构建靶向EGFR的PA脂质体纳米颗粒(EGFR-PA-NP)。②将人NSCLC A549细胞(2×106个/只)接种于裸鼠腋下,建立肺癌异种皮下移植瘤裸鼠模型。10只模型裸鼠随机分为PA脂质体纳米颗粒(PA-NP)组和EGFR-PA-NP组(n=5),分别尾静脉注射给予20 mg·kg^(-1)相应药物,24 h后剥取肿瘤、癌旁、肝、肺、心、脑、肾、脾、胃、小肠等组织,液相色谱-质谱(LC-MS)法检测药物在体内的组织分布情况。③20只模型裸鼠随机分为模型组(100μL)、PA组(15 mg·kg^(-1))、PA-NP组(15 mg·kg^(-1))和EGFR-PA-NP组(15 mg·kg^(-1))(n=5),分别尾静脉注射给予相应干预,隔日1次,共28 d。28 d后观察药物对裸鼠皮下移植瘤生长的影响。通过原位末端转移酶标记(TUNEL)检测法检测皮下移植瘤中肿瘤细胞凋亡情况,免疫荧光染色法检测皮下移植瘤中血小板-内皮细胞黏附分子(CD31)表达情况,免疫组化染色法和Western blot法检测皮下移植瘤中蛋白激酶B(Akt)、磷酸化(p)-Akt、哺乳动物雷帕霉素靶蛋白(mTOR)和p-mTOR表达水平。结果①制备的EGFR-PA-NP粒径为(122±6.90)nm、Zeta电位为(-24.28±3.76)mV、包封率为85.24%、载药量为8.09%,符合纳米颗粒特征。②LC-MS法检测药物组织分布结果显示,EGFR-PA-NP组药物在裸鼠瘤体内的富集量是PA-NP组的3倍,显著高于PA-NP组(P<0.05)。③在裸鼠A549皮下移植瘤模型中,PA组、PA-NP组和EGFR-PA-NP组裸鼠瘤体体积明显小于模型组(P<0.05),而EGFR-PA-NP组瘤体体积明显小于PA-NP组(P<0.05)。与PA-NP组相比,EGFR-PA-NP组肿瘤中凋亡细胞数量显著增加(P<0.05),CD31蛋白表达水平显著降低(P<0.05),并且p-Akt、p-mTOR表达水平显著降低(P<0.05)。结论EGFR-PA-NP能够通过促进肿瘤细胞凋亡、抑制肿瘤血管新生发挥抗肺癌作用,其机制与抑制Akt/mTOR通路激活相关。