Increased intestinal permeability in inflammatory bowel diseases assessed by iohexol test

AIM:To study intestinal permeability(IP) and its relationship to the disease activity in patients with inflammatory bowel diseases(IBD)-Crohn's disease(CD) and ulcerative colitis(UC).METHODS:Fifty-eight patients with active IBD(32 with CD and 26 with UC) and 25 healthy controls consented to participate in the study.The clinical activity of CD was estimated using the Crohn's Disease Activity Index(CDAI),and the endoscopic activity of UC using the Mayo scoring system.IP was assessed by the rise in levels of iohexol,which was administered orally(25 mL,350 mg/mL) 2 h after breakfast.Three and six hours later serum(SIC mg/L) and urine(UIC g/mol) iohexol concentrations were determined by a validated HPLC-UV technique.RESULTS:In the CD group,SIC values at 3 h(2.95 ± 2.11 mg/L) and at 6 h after ingestion(2.63 ± 2.18 mg/L) were significantly higher compared to those of healthy subjects(1.25 ± 1.40 mg/L and 1.11 ± 1.10 mg/L,respectively,P < 0.05).UIC(g/mol) values were also higher in patients,but the differences were significant only for UIC at 6 h.Significant positive correlation(P < 0.05) was found between the CDAI and IP,assessed by SIC at 3 h(r = 0.60) and 6 h(r = 0.74) after the ingestion.In comparison to controls,SIC and UIC of UC patients were higher in the two studied periods,but the differences were significant at 6 h only.Significantly higher values of SIC(P < 0.05) were found in patients with severe endoscopic activity of UC compared to those of patients with mild and moderate activity(3.68 ± 3.18 vs 0.92 ± 0.69 mg/L).CONCLUSION:Serum levels of iohexol at 3 h and 6 h after its ingestion reflect increased IP,which is related to the disease activity in patients with IBD.

Determination of iohexol by capillary blood microsampling and UHPLC-MS/MS

One of the most important tools used to evaluate kidney function in the context of chronic kidney disease or other renal function related pathologies is the exploration of glomerular filtration rate (GFR). Iohexol is up to this moment a good candidate molecule for the GFR assessment since it exhibits minimum protein binding rates and minimum extra-renal clearance, being neither secreted nor reabsorbed at the tubular level. This study proposes and evaluates a new LC-MS/MS method for the iohexol determination from capillary blood, prelevated using volumetric absorbative microsampling (VAMS) systems. As an alternative to VAMS, a brand new HemaPEN■ device for micro-prelevation was also tested. A new high throughput sample preparation protocol adapted for iohexol quantification from whole blood VAMS samples was developed. The medium term stability study of iohexol in dried whole blood VAMS samples that was conducted showed a good stability of this molecule for up to 12 days. By collecting only 10 mL of blood, iohexol can be analyzed from dried whole blood VAMS samples for concentration ranges between 1 and 250 mg/mL. Due to the analyte stability in VAMS for up to 12 days, this approach might be successfully applied for GFR assessment for clinical cases allowing minimum invasiveness and even delayed analysis.

Iohexol plasma and urinary concentrations in cirrhotic patients:A pilot study

BACKGROUND Renal failure is an independent prognostic factor for survival in patients with cirrhosis.Equations to calculate serum creatinine significantly overestimate the glomerular filtration rate(GFR).Plasma clearance of direct biomarkers has been used to improve the accuracy of evaluations of GFR in this population,but no study has simultaneously measured plasma and urinary clearance,which is the gold standard.AIM To study calculated plasma and urinary concentrations of iohexol,based on the kinetics of samples collected over 24 h from cirrhotic patients with three different grades of ascites.METHODS One dose of iohexol(5 mL)was injected intravenously and plasma concentrations were measured 11 times over 24 h in nine cirrhotic patients.The urinary concentration of iohexol was also measured,in urine collected at 4,8,12 and 24 h.RESULTS The plasma and urinary curves of iohexol were similar;however,incomplete urinary excretion was detected at 24 h.Within the estimated GFR limits of our population(>30 and<120 mL/min/1.73 m^(2)),the median measured GFR(m GFR)was 63.7 mL/min/1.73 m^(2)(range:41.3–111.3 mL/min/1.73 m^(2)),which was an accurate reflection of the actual GFR.Creatinine-based formulas for estimatingGFR showed significant bias and imprecision,while the Brochner–Mortensen(BM)equation accurately estimated the m GFR(r=0.93).CONCLUSION Plasma clearance of iohexol seems useful for determining GFR regardless of the ascites grade.We will secondly devise a pharmacokinetics model requiring fewer samples andvalidate the BM equation.

Iohexol尿路造影

以往的研究似乎未能证实非离子型造影剂在尿路造影中的优点（译者按:所用药物为Metriza-mide 和Iopamide）。本文报导一组肾功能正常病人的Iohexol 尿路造影,并与泛影钠进行比较。Iohexol 也是一种非离子型造影剂,其渗压为880mOsm/KgH2O（图1,A）;而泛影酸的渗压高达2200mOsm/kgH2O（图1,B）。将连续60例用双盲法随机抽样分为二组,分别静脉注射Iohexol 和泛影钠300mg/kg,采用18号针头,注射时间为30秒。注射前及注射后1小时,

非离子型造影剂iohexol血浆清除率单点检测法测定肾小球滤过率

目的 用非离子型造影剂iohexol血浆清除率检测肾小球滤过率(GFR)。方法 选择93例各种肾脏病患者,男45例,女48例,年龄12-80岁,清晨空腹注射iohexol 5ml,4 h后留取血样,高效液相(HPLC)法检测血浆iohexol浓度,应用Jacobsson和Bubeck两种一室分布的数学模型,计算iohexol血浆清除率,以99mTc-GFR作为检测GFR的金标准,对两者进行比较。结果 Jacobsson法算得iohexol-GFR与99mTc-GFR相关系数为r=0.85,标准误为16.06 ml/min;Bubeck法算得iohexol-GFR与99mTc-GFR相关系数为r=0.82,标准误为17.75 ml/min。在早期肾功能不全的患者中,iohexol-GFR较Scr、Ccr能更敏感反映肾功能减退。结论 应用Jacobsson和Bubeck两种模型单点法计算iohexol血浆清除率是检测GFR的简便、准确的方法。

Assessment of the potential interactions between favipiravir and radiocontrast agents

BACKGROUND In cases of coronavirus disease 2019(COVID-19),favipiravir is commonly included to the therapy regimen.Drug interactions between favipiravir and other COVID-19 therapy drugs are frequently researched.However,no research on possible drug interactions between Favipiravir and radiocontrast agents,which have become almost crucial in diagnostic processes while not being part of the treatment,has been found.AIM To determine potential medication interactions between Favipiravir and radiocontrast agents.METHODS The study comprised patients who were taking Favipiravir for COVID-19 therapy and underwent a contrast-enhanced computed tomography(CT)or magnetic resonance imaging(MRI)test while taking the medicine.The computerized patient files of the cases included in the study,as well as the pharmacovigilance forms in the designated hospital,were evaluated for this purpose.RESULTS The study included the evaluation of data from 1046 patients.The study sample's mean age was 47.23±9.48 years.The mean age of cases with drug interactions was statistically significant greater than that of cases with no drug interactions(P=0.003).When evaluated with logistic regression analysis,a 1-year raises in age increases the risk of developing drug interactions by 1.63 times(P=0.023).There was no statistically significant difference in the occurrence of medication interactions between the sexes(P=0.090).Possible medication interactions were discovered in 42 cases(4%).CONCLUSION The findings of this study revealed that the most notable findings as a result of the combined use of contrast agents and favipiravir were increased creatinine and transaminase values,as well as an increase in the frequency of nausea and vomiting.The majority of drug interactions discovered were modest enough that they were not reflected in the clinic.Drug interactions become more common as people get older.

Contrast-induced ischemic colitis following coronary angiography:A case report

BACKGROUND Ischemic colitis(IC)is common,rising in incidence and associated with high mortality.Its presentation,disease behavior and severity vary widely,and there is significant heterogeneity in therapeutic strategies and prognosis.The common causes of IC include thromboembolism,hemodynamic insufficiency,iatrogenic factors and drug-induced.However,contrast-induced IC,especially isolated right colon ischemia is rarely reported.CASE SUMMARY A 52-year-old man was admitted to the hospital due to intermittent chest distress accompanied by palpitation.Coronary angiography was performed using 60 mL of the iodinated contrast agent iohexol(Omnipaque 300),and revealed moderate stenosis of the left anterior descending artery and right coronary artery.At 3 h post-procedure,he complained of epigastric pain without fever,diarrhea and vomiting.Vital signs remained normal.An iodixanol-enhanced abdominal computed tomography(CT)scan revealed thickening,edema of the ascending and right transverse colonic wall and inflammatory exudate,without thrombus in mesenteric arteries and veins.Following 4 days of treatment with antibiotic and supportive management,the patient had a quick and excellent recovery with disappearance of abdominal pain,normalization of leucocyte count and a significant decrease in C reactive protein.There was no recurrence of abdominal pain during the patient's two-year follow-up.CONCLUSION This case emphasizes that contrast-induced IC should be considered in the differential diagnosis of unexplained abdominal pain after a cardiovascular interventional procedure with the administration of contrast media.Timely imaging evaluation by CT and early diagnosis help to improve the prognosis of IC.

犬心脏、肺动脉CT造影技术研究

[目的]本研究旨在确定犬心脏、肺动脉CT血管造影最佳造影方案。[方法]造影时对于同一体型的犬固定注射持续时间和注射速率,采用不同质量浓度的碘海醇对心脏、肺动脉血管进行造影。心脏造影碘海醇浓度(以碘含量计):小型犬,100~200 mg·mL-1;中型犬,200~300 mg·mL-1;大型犬,250~350 mg·mL-1。肺动脉造影碘海醇质量浓度:小型犬,50~100 mg·mL-1;中型犬,50~100 mg·mL-1;大型犬,150~200 mg·mL-1。犬麻醉后头静脉注射造影剂,动态扫描,获取感兴趣区域时间-密度曲线,确定扫描延迟时间,心脏造影采用主动脉窦CT值>200 HU的时间作为扫描延迟时间,肺动脉造影采用肺动脉干CT值峰值时间作为扫描延迟时间,然后进行容积扫描,获得造影图像。采用定量和定性的方法对不同造影方案获得的图像进行评价,确定最佳造影方案。[结果]心脏造影条件:小型犬:200 mg·mL-1碘海醇10 mL,生理盐水5 mL,注射速率1 mL·s-1;中型犬:250 mg·mL-1碘海醇15 mL,生理盐水10 mL,注射速率1 mL·s-1;大型犬:350 mg·mL-1碘海醇30 mL,生理盐水20 mL,注射速率1 mL·s-1。肺动脉造影条件:小型犬:75 mg·mL-1碘海醇15 mL,生理盐水15 mL,注射速率5 mL·s-1;中型犬:100 mg·mL-1碘海醇20 mL,生理盐水20 mL,注射速率5 mL·s-1;大型犬:175 mg·mL-1碘海醇30 mL,生理盐水30 mL,注射速率5 mL·s-1。在这些条件下得到的血管增强后的CT值较高,且图像质量高,造影效果良好。[结论]本试验所使用的造影剂条件可获得满意且利于临床诊断的图像,可用于犬心脏、肺动脉疾病的CT造影检查。

碘海醇致全脑血管造影术后药物不良反应致死1例

通过病例报告提高对碘对比剂不良反应的认识及探讨诊治体会。回顾性分析1例因用碘海醇注射液行全脑血管造影术即数字减影血管造影(DSA)导致死亡案例的临床资料,并结合文献进行分析。患者经扩容、升压、抗炎抗过敏、胸外按压、呼吸机辅助呼吸等处理后,最终抢救无效死亡。在碘造影剂的使用过程中应熟悉其不良反应,无论在使用前、使用过程中还是使用后都应做好预防、观测、监护工作,及时应对不良反应的发生。

高效液相色谱法测定碘海醇原料药中的杂质含量

建立了碘海醇API中杂质G和杂质S(同分异构体杂质)的HPLC分析方法。方法:色谱柱为Agilent ZORBAX SB-Aq型C18柱(4.6×250mm,5μm),流动相为乙腈-0.1%磷酸溶液(4:96),柱温为25℃,检测波长为254nm,流速为1.0mL/min,进样量为10μL,进样时间为60min。结果:碘海醇杂质G在0.0692~2.799μg/mL的范围内呈线性,碘海醇杂质S在0.0188~3.852μg/mL的范围内呈线性,线性相关系数均大于0.995,检测下限均不高于0.05μg/mL。准确度实验表明,两种杂质的平均回收率分别为98.4%和116.4%。供试品溶液在室温放置49h内,两种杂质均十分稳定。不同柱温、流动相、流速及色谱柱条件下,测定结果未见明显差异。结论:本文所建立的高效液相色谱测试方法简单准确、重复性好、灵敏度高,可用于碘海醇原料药中的杂质G和异构体杂质S含量测定。

电位滴定法测定碘海醇注射液中氨丁三醇含量

目的建立检测碘海醇注射液中氨丁三醇含量的电位滴定法。方法采用电位滴定法,以稀盐酸为溶剂,用氢氧化钠滴定液滴定,以两次突跃点消耗氢氧化钠滴定液的容积差值计算氨丁三醇含量。结果氨丁三醇在0.6~1.8 mg·mL^(-1)的浓度范围内与滴定液消耗体积呈良好线性关系(r=0.9998);平均回收率为102.8%,RSD为1.4%。结论本方法简单、灵敏、准确,可用于碘海醇注射液中氨丁三醇的含量检测。

非离子型X－CT造影剂碘海醇的合成

报道了非离子型Ｘ－ＣＴ造影剂碘海醇（ｉｏｈｅｘｏｌ）的化学合成。产物经元素分析、红外光谱、核磁共振谱、质谱和快原子轰击质谱等测定，与结构完全一致。

碘海醇注射液致呼吸心跳骤停死亡1例

碘海醇（iohex01）为新一代非离子型造影剂，其渗透压低，不足离子型造影剂的1／2；不形成离子，没有阳离子的生物学作用，因此认为其不良反应较轻。其不良反应主要表现胃肠道反应如恶心、呕吐等，过敏样反应如皮肤过敏反应皮疹、荨麻疹、红斑等；致死反应非常少见。本文报道1例碘海醇注射液引起呼吸心跳骤停死亡的病例。

碘海醇的合成工艺改进

改进了碘海醇合成工艺中的关键步骤。在用醋酐酰化时用吡啶代替硫酸 ;在选择性水解时用氨水代替氢氧化钠 ;在 5 -位氮烷基化时用溶媒乙二醇单甲醚代替 1,2 -丙二醇。改进后的工艺反应条件温和、副反应少、易于操作 ,适于工业化生产 ,总收率 60 .8%。

碘海醇所致造影剂肾病的危险因素分析

目的分析碘海醇所致造影剂肾病(CIN)的危险因素。方法收集在河北医科大学第一医院心内科行经皮冠状动脉造影的646例患者临床资料,根据造影剂肾病的诊断标准分为CIN组(n=116)和非CIN组(n=530),比较两组患者基础疾病、自身情况的差异,采用Logistic回归分析危险因素。结果 CIN组患者和非CIN组患者的2型糖尿病、慢性肾脏病、心力衰竭、低血压、心肌梗死、急诊PCI例数以及年龄、造影剂用量差异有统计学意义(P<0.05)。Logistic回归分析显示:2型糖尿病、慢性肾脏病、心力衰竭、低血压、心肌梗死、年龄≥70岁、造影剂用量≥200 ml、急诊PCI是发生造影剂肾病的危险因素。结论碘海醇所致造影剂肾病的发生受到基础疾病、自身情况、造影剂用量等因素的影响,对于存在CIN高危因素的患者应引起临床上的高度重视。

肾小球滤过率的测定方法及其临床应用

肾小球滤过率(GFR)是衡量肾功能的最佳指标,在临床工作中具有重要的参考价值,其数值是否准确对诊疗决策的优化影响重大。GFR可以通过估算公式或直接测量获得,估算肾小球滤过率(eGFR)在特定情况或特殊人群中易出现偏倚,采用直接测量的GFR(mGFR)评价肾功能更为准确。结合菊粉、肌酐、碘海醇、99m锝-二乙烯三胺五醋酸(99mTc-DTPA)、51铬-乙二胺四乙酸、125I-碘肽酸盐等常用肾小球滤过标志物的不同特性,可分别采用血、尿清除率或肾动态显像法测量mGFR,但所得结果的准确性不一。鉴于其它方法的耗时繁琐,临床应用多选择内生肌酐清除率(Ccr)对肾功能进行评估,但综合各项研究证实Ccr存在显著偏倚,易高估GFR。尿液碘海醇清除率、99mTc-DTPA清除率的准确性较高,更适宜推广于临床。GFR测量方法作为各类eGFR公式的验证手段,在临床工作中的应用和评价不容忽视,值得进一步研究。

碘海醇在冠脉介入治疗中对肾功能的影响及相关护理

目的探讨低渗造影剂碘海醇对冠脉介入治疗患者肾功能的影响,以及水化对肾功能的影响,并总结护理要点。方法将320例冠脉介入患者按肾功能情况分为肾功能正常组(A组)和肾功能轻度损害组(B组)。其中,A组190例分为水化组90例和对照组(非水化组)100例;B组130例分为水化组74例和对照组56例。水化组术前术后静脉补充0.9%氯化钠注射液,对照组不额外静脉补液。术前及术后第1天、第3天、第6天监测血肌酐(Scr)、尿素氮(BUN)、尿量并实施相关的护理措施。结果 A组患者术后第1天、第3天的BUN和Scr与造影前相比,差异无显著意义(P>0.05)。B组患者术后第1天、第3天对照组的BUN和Scr显著高于造影前水平(P<0.05);与水化组相比,对照组术后第1天、第3天的BUN和Scr也明显升高,差异有显著意义(P<0.05)。对照组中术后第6天的BUN和Scr较其术后第1天显著降低(P<0.05)。结论碘海醇对肾功能有损害的患者影响较大,采取合理的水化和精心的护理可以减轻对肾功能的损伤,减少造影剂肾病的发生。

多模态MR与CT小肠造影在小肠肿瘤性疾病诊断中的应用

目的比较多模态MR与CT小肠造影诊断小肠肿瘤性疾病的应用价值。方法以60例疑有小肠肿瘤性疾病患者作为研究对象,由两位有资质的影像科医师对CT和MR图像进行阅片,从肠壁形态、病变部位(十二指肠、近段回肠、远段回肠、近段空肠、远段空肠)及累及范围进行分析,并与手术及内镜活检病理结果对照。结果 60例患者经手术及内镜活检证实有33例患者存在35处小肠肿瘤性病灶(5例腺癌、6例淋巴瘤、18例间质瘤、3例神经内分泌肿瘤、2例海绵状血管瘤及1例脂肪瘤);CT对小肠肿瘤性疾病诊断的特异度、敏感度及准确度分别为100%(27/27)、90.9%(30/33)、95.0%(57/60),MR分别为100%(27/27)、97.0%(32/33)、98.3%(59/60),两者的诊断效能相近。结论多模态MR与CT小肠造影均是小肠肿瘤性疾病的有效诊断手段,值得在临床上推广应用。

脑血管造影(DSA)术后碘海醇脑病的临床及2年随访

目的探讨碘海醇脑病的各项临床特征及其可能相关原因及治疗预后。方法报道1例用碘海醇行脑血管造影(DSA)术,术后通过影像学检查临床诊断为碘海醇脑病并随访2年的病例,综合相关研究文献,分析其临床表现、辅助检查、治疗及预后等情况。结果碘海醇致碘海醇脑病患者呈急性或亚急性起病;有脑实质损害的症状和体征,常伴有不同程度的意识障碍;脑脊液(CSF)正常或轻度异常;脑电图示不同程度弥漫性或局灶性慢波;脑核磁共振(MRI)双侧大脑半球皮层及皮层下白质区、基底节区、脑室旁及半卵圆中心长或略长T1信号、长T2信号;皮质激素治疗效果较明显;随访2年无复发。结论碘海醇致碘海醇脑病呈单相病程,临床表现多变,脑部病灶分布散在而广泛,头颅MRI检查对于明确诊断较为重要,激素治疗疗效佳,随访无复发,预后好。

子宫腔碘水加压法输卵管再通术的临床研究

目的寻求一种简便快速、安全有效、经济实用,将造影诊断与输卵管再通治疗结合起来的新方法。方法应用双腔球囊胶管插入子宫腔,充盈球囊堵塞子宫颈内口,用助推器注入碘海醇充盈子宫腔及输卵管,电视动态观察实时点片,完成造影诊断。当发现输卵管阻塞时,用手助推加压,逐渐增高宫腔内压力,使阻塞输卵管被造影剂压力钝性开通。结果本组2698例,插管成功2685例。其中,原发不孕806例,继发不孕1868例,其他24例,输卵管阻塞3082支(右1561支、左1521支),占实有输卵管的59%,加压开通率为77.8%(2397/3082);通而不畅343支(右175支、左168支),加压开通率:93.9%(322/343),出现静脉逆流27例。除局部疼痛及少量阴道流血外,无严重并发症病及病死率。结论该法简便快速,安全有效,经济实用,将造影诊断与输卵管再通相结合,深受患者欢迎,值得推广应用。