CYP2C19基因多态性与缺血性脑卒中发病及预后的相关性

目的探讨细胞色素P450药物代谢酶(CYP)2C19基因多态性对老年缺血性脑卒中(ISS)发病及预后的影响。方法将2014年1月至2016年6月收治的老年ISS患者120例作为ISS组,另选取同期健康体检者120例作为对照组,ISS组给予氯吡格雷75 mg/d持续治疗12个月,采用聚合酶链式反应-限制性片段长度多态性法(PCR-RFLP)检测CYP2C19基因型,血栓弹力图法检测ISS组血小板聚集抑制率,分析CYP2C19基因型与ISS发生、氯吡格雷抵抗的相关性,并对预后影响因素进行非条件多因素Logistic回归分析。结果 ISS组CYP2C19 G681A位点AA型基因、G636A位点AA型、AG型基因频率显著高于对照组,差异有统计学意义(P0.05);氯吡格雷抵抗组CYP2C19基因G681A位点AG型、AA型频率显著高于敏感组,差异有统计学意义(P0.05);多因素Logistic回归分析显示糖尿病、氯吡格雷抵抗、携带CYP2C19基因G681A位点AA型是老年ISS患者不良预后的独立危险因素(P0.05)。结论 CYP2C19老年G681A位点AA型基因及G636A位点AA型、AG型基因是老年ISS发病的易感基因,而CYP2C19 G681A位点AG型、AA型基因与氯吡格雷抵抗密切相关。此外,G681A位点AA型基因是老年ISS患者不良预后的独立危险因素。     

SLCO1B1c.388A＞G多态性对于中国缺血性卒中患者阿托伐他汀降脂和抗动脉粥样硬化作用的影响

目的 探讨溶质载体有机阴离子转运体家族1B1(solute carrier organic anion transporterfamily member l B1,SLCO1 B1)基因c.388A＞G多态性对中国缺血性卒中患者阿托伐他汀降脂和抗动脉粥样硬化作用的影响.方法 前瞻性纳入基线低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)＞ 1.8 mmol/L的缺血性卒中患者,口服阿托伐他汀(20 mg/d)治疗12个月,分别在治疗前后检测血脂和双侧颈动脉内膜-中膜厚度(carotid intima-media thickness,CIMT).比较SLCO1 B1基因c.388A＞G基因型组之间CIMT的差异.结果 共纳入71例缺血性卒中患者,其中AA基因型5例,AG基因型31例,GG基因型35例;A等位基因频率为28.9％,G等位基因频率为71.1％.所有患者治疗后总胆固醇、三酰甘油和LDL-C均较治疗前显著降低,而高密度脂蛋白胆固醇显著升高(P均＜0.001),但CIMT无显著改变(P=0.475).GG基因型组LDL-C＜ 1.8 mmol/L或LDL-C下降≥50％的患者比例显著高于AG+AA基因型组(74.29％对44.44％;x2=6.540,P=0.011).结论 SLCO1B1基因c.388A＞G多态性会影响阿托伐他汀的降脂效果,GG基因型组的降脂效果优于AG+AA基因型组;SLCO1 B1基因c.388A＞G多态性对阿托伐他汀抗动脉粥样硬化疗效无影响,但可能与随访时间过短有关.     

肾素-血管紧张素-醛固酮系统基因多态性与大动脉粥样硬化性卒中的相关性:中国南方汉族人群研究

目的 研究肾素-血管紧张素-醛固酮系统血管紧张素原(angiotensinogen,AGT)基因M235T、血管紧张素Ⅱ1型受体(angiot ensinⅡtype 1 receptor,AGTR1)基因A1166C、醛固酮合酶( aldosterone synthase,CYP11B2)基因- 344C/T多态性与中国南方汉族人群大动脉粥样硬化性卒中(large-artery atherosclerosis,LAA)的相关性.方法 采用聚合酶链反应和基因测序技术对中国南方汉族LAA患者和正常对照者AGT基因M235T、ATGR1基因A1166C和CYP11B2基因- 344C/T多态性进行基因分型,并通过二分类logistic回归分析确定这3种基因多态性与LAA的相关性.结果 共纳入LAA患者107例和142名健康对照者.LAA组AGT基因235TT基因型(66.36％对50.70％,x2=6.122,P=0.047)和T等位基因(79.44％对70.07％,x2=5.581,P=0.018)频率显著高于对照组,AGTR1基因1166CC基因型(0％对0％,x2=1.494,P=0.222)和C等位基因(7.48％对4.93％,x2=1.399,P=0.237)频率与对照组无显著性差异,CYP11B2基因- 344CC基因型(9.35％对4.23％,x2=3.603,P=0.165)和C等位基因(27.10％对26.06％,x2=0.069,P=0.793)频率与对照组亦无显著性差异.二分类logistic回归分析显示,这3种基因多态性与单纯性LAA患病均无显著相关性.合并高血压的LAA患者AGT基因235TT基因型(68.00％对41.90％,x2=12.446,P=0.002)和T等位基因(79.33％对64.76％,x2=8.993,P=0.003)频率均显著高于血压正常对照组,logistic回归分析显示,暴露于TT基因型的优势比(odds ratio,OR)为2.153[ 95％可信区间(confidence interval,CI)0.789 ～5.872],T等位基因的OR值为2.089(95％ CI1.285 ～3.396).结论 AGT基因M235T多态性与南方汉族人群单纯性LAA无关,但可能与合并高血压的LAA患病风险相关;CYP11B2基因- 344C/T多态性和AGTR1基因A1166C多态性与南方汉族人群LAA发病无关.     

XYLB基因rs17118多态性与中国汉族人群缺血性卒中关联研究

目的 验证木酮糖激酶(xylulokinase homolog,XYLB)基因rs17118多态性与中国汉族人群缺血性卒中发病风险的关联性.方法 采用病例对照研究设计,病例组为首发缺血性卒中患者,对照组为医院体检者,采用Taqman探针荧光定量聚合酶链反应技术检测rs17118 C/A多态性的基因型分布.结果 共纳入475例缺血性卒中患者和483例对照者.病例组高血压(67.9％对22.2％;x2 =292.982,P＜0.001)、糖尿病(24.2％对7.3％;x2 =25.864,P＜0.001)的患者比例以及三酰甘油[(1.649±1.126)mmol/L对(1.157土1.480)mmol/L);t=3.592,P＜0.001]和低密度脂蛋白胆固醇[(3.499±1.163) mmol/L对(3.105±0.627) mmol/L;t=-6.227,P＜0.001]水平显著高于对照组,但总胆固醇水平显著低于对照组[(5.144±1.296)mmol/L对(5.491±1.335)mmol/L;t=4.650,P＜0.001].病例组AA基因型(11.4％对7.5％;x2=6.136,P=0.016)以及A等位基因(32.3％对26.4％;x2 =8.093,P=0.005)频率均显著高于对照组.多变量logistic回归分析显示,在校正传统危险因素后,AA基因型携带者的缺血性卒中患病风险是CC基因型携带者的1.971倍(优势比1.971,95％可信区间1.040 ～3.736;P =0.038).结论 XYLB基因rs187118C/A多态性与中国汉族人群缺血性卒中的发病风险有关.     

血小板膜糖蛋白Ⅱb HPA-3基因多态性与中国汉族人缺血性卒中的相关性

目的 探讨天津市汉族人群血小板膜糖蛋白(glycoprotein,GP)Ⅱb HPA-3基因多态性的分布情况及其与缺血性卒中的关系.方法 缺血性卒中组150例,对照组135例,应用聚合酶链反应-限制性内切酶片段长度多态性方法进行基因分型,并抽样测序验证.比较各基因型和等位基因频率分布及其与缺血性卒中的关系.结果 病例组ab基因型、bb基因型和b等位基因频率均显著高于对照组(P =0.000),而aa基因型和a等位基因频率则显著低于对照组(P=0.000).病例组不同性别和年龄组之间GPⅡb基因型和b等位基因频率无显著性差异;虽然各病因学亚型之间基因型频率无显著性差异,但大动脉粥样硬化性卒中亚组b等位基因频率显著高于小血管闭塞性卒中亚组和心源性脑栓塞亚组(61.8％对46.7％对47.5％x2 =6.573,P=0.037).多变量logistic回归分析显示,高血压(优势比7.475,95％可信区间3.700 ～ 15.003;P=0.000)和b等位基因(优势比3.678,95％可信区间1.245～10.863,P=0.018)是缺血性卒中发生的独立危险因素.结论 血小板膜GPⅡb HPA-3基因多态性可能与缺血性卒中发生风险相关,携带b等位基因可能是缺血性卒中的独立危险因素,尤其是大动脉粥样硬化性卒中.     

细胞色素P450基因变异与氯吡格雷抵抗及血管事件相关性

目的探讨细胞色素P450(cytochrome P450,CYP)相关基因多态性与氯吡格雷抵抗及随访期血管事件的相关性。方法连续纳入2014年6月~2015年1月接受氯吡格雷治疗的375例脑梗死患者。治疗前及治疗后7~10d检测血小板聚集率,采用质谱法检测8个CYP基因位点的多态性,多因子降维法分析基因-基因之间的交互作用,所有患者随访6个月。根据入组患者是否存在氯吡格雷抵抗分为:氯吡格雷抵抗组153例和氯吡格雷敏感组222例。结果氯吡格雷抵抗组CYP3A5(rs776746)GG+AG及CYP2C19*2(rs4244285)AG+AA基因型频率分布明显高于氯吡格雷敏感组,CYP3A5GG和CYP2C19*2AA基因型组合使氯吡格雷抵抗风险增加了2.23倍(OR=2.23,95%CI:1.08~5.87,P=0.025),且为原发终点发生的危险因素,CYP3A5GG和CYP2C19*2AA交互基因型者血小板聚集抑制率明显低于未携带者[(32.58±10.23)%vs(53.84±17.25)%,P=0.000]。结论CYP450相关基因变异及其交互作用与氯吡格雷抵抗和随访期血管事件发生相关。     

连接蛋白37基因C1019T多态性与缺血性卒中及其转归的相关性

目的 探讨连接蛋白37(connexin37,Cx37)基因C1019T多态性与缺血性卒中及其转归的关系.方法 采用限制性片段长度多态性分析技术检测缺血性卒中组和对照组Cx37基因C1019T多态性的分布,采用改良Rankin量表(modified Rankin Scale,mRS)评价发病后3个月时神经功能转归.结果 纳入急性缺血性卒中患者232例,其中转归良好(mRS评分＜3分)210例,转归不良(mRS评分≥3分)22例;对照组235例.缺血性卒中组TT基因型(12.93％对6.39％;x2=10.087,P=0.006)和T等位基因(31.25％对21.49％;x2 =11.466,P=0.001)频率显著高于对照组.多变量logistic回归分析显示,TT基因型[优势比(odds ratio,OR)5.794,95％可信区间(confidence interval,CI)1.405～23.894;P=0.015]和T等位基因(OR 131.016,95％ CI 6.943～2472.477;P =0.001)可显著增高缺血性卒中的发病风险.单因素分析显示,TT基因型(OR 0.650,95％ CI 0.144～2.934;P=0.575)、CT基因型(OR 0.622,95％ CI 0.234～1.655;P=0.342)、CC基因型(OR 0.654,95％ CI0.268～1.595;P=0.350)与缺血性卒中转归均无显著相关性.结论 Cx37 1019TT基因型和T等位基因可增高缺血性卒中风险,T等位基因是缺血性卒中的遗传易感因素之一,但其基因多态性与缺血性卒中发病3个月时的转归无关.     

脂蛋白相关磷脂酶 A2基因 R92 H多态性与中国山东地区汉族人群缺血性卒中及其亚型的相关性

目的：探讨脂蛋白相关磷脂酶A2（lipoprotein-associatedphospholipaseA2,Lp-PLA2）基因多态性位点R92H与中国山东地区汉族人群缺血性卒中及其亚型的相关性。方法纳入中国山东地区386例首次发病的缺血性卒中患者和386名健康对照组,根据TOAST 标准将患者进一步分为大动脉粥样硬化性卒中（ large artery atherosclerotic, LAA）和小动脉闭塞性卒中（ smal artery occlusion, SAO）。采用酶联免疫吸附法测定血清Lp-PLA2水平,聚合酶链反应及基因直接测序法测定R92H基因多态性。结果缺血性卒中组、LAA组和SAO组血清Lp-PLA2水平均高于对照组,差异有统计学意义（P均<0.01）。缺血性卒中组GA（P=0.006）、AA（P=0.020）、AA+GA基因型（P=0.009）以及A等位基因（P=0.001）分布频率均显著高于对照组,LAA组GA+AA基因型（P=0.007）及A等位基因（P<0.001）分布频率与对照组相比亦存在统计学差异,而SAO 组则不然。多变量logistic回归分析显示,GA+AA基因型[优势比（odds ratio, OR）1.43,95％可信区间（confidence interval, CI）1.02~2.00;P=0.029]、GA基因型（OR 1.42,95％CI 1.01~2.00;P=0.037）及A等位基因（OR 1.44,95％CI 1.11~2.18;P=0.028）是缺血性卒中发病的独立危险因素。 GA+AA 基因型（ OR 1.73,95％CI 1.18~2.55;P<0.001）和GA基因型（OR 1.67,95％CI 1.13~2.48;P<0.001）是LAA的独立危险因素,而与S AO 无显著独立相关性。结论缺血性卒中患者血清Lp-PLA2水平升高, LAA组升高最明显;R92H基因多态性可能与中国山东地区汉族人群缺血性卒中的易感性有关。     

ATP结合盒转运体A1基因R219K多态性与中国人缺血性卒中风险:汇总分析

目的 探讨ATP结合盒转运体A1(ATP-binding cassette transporter A1,ABCA1)基因R219K多态性与中国人缺血性卒中的相关性.方法 采用全面的文献检索收集2013年5月以前发表的中国人ABCA1基因R219K多态性与缺血性卒中相关性的病例对照研究.采用Stata 11.0软件包进行汇总分析.采用优势比(odds ratio,OR)及其95％可信区间(confidence interval,CI)评价基因多态性与缺血性卒中的关联强度.结果 共10项研究符合条件纳入分析,包括病例组1 619例,对照组1 907例,入选文献无明显偏倚.汇总分析显示,RK+KK基因型携带者缺血性卒中风险较RR基因型携带者显著性降低8％(OR0.92,95％ CI 0.88～0.96;P =0.000);KK基因型携带者的缺血性卒中风险较RR基因型携带者显著性降低36％(OR 0.64,95％ CI 0.44～0.94;P=0.02);RK基因型携带者的缺血性卒中风险较RR基因型携带者显著性降低19％(OR0.81,95％ CI 0.69～0.95;P=0.009);K等位基因携带者的缺血性卒中风险较R等位基因携带者显著性降低17％(OR 0.83,95％ CI 0.69～0.99;P=0.036).结论 ABCA1基因R219K多态性与中国人缺血性卒中易感性相关,K等位基因可能是中国人缺血性卒中的遗传保护性因素.     

血小板膜糖蛋白Ⅱb HPA-3多态性与天津地区汉族人群缺血性卒中风险和转归的相关性

目的 探讨血小板膜糖蛋白(glycoprotein,GP)ⅡbHPA-3基因多态性与天津地区汉族人群缺血性卒中发病风险和转归的相关性.方法 连续纳入急性缺血性卒中患者和性别、年龄相匹配的健康体检者.采用聚合酶链反应-限制性片段长度多态性方法检测GPⅡbHPA-3基因多态性.转归不良定义为6个月时改良Rankin量表评分＞2分.结果 共纳入224例急性缺血性卒中患者和98例性别、年龄相匹配的健康体检者.急性缺血性卒中组bb基因型(45.09％对15.06％;x2=40.618,P＜0.001)和b等位基因(63.84％对33.67％;x2 =50.064,P＜0.001)频率显著高于对照组;多变量logistic回归分析显示,bb基因型是缺血性卒中的独立危险因素(优势比5.838,95％可信区间2.653～ 12.843;P＜0.001).在各TOAST亚型中,大动脉粥样硬化型组bb基因型(x2=10.912,P=0.028)和b等位基因(x2 =11.801,P=0.019)频率显著高于其他各组.转归不良组大动脉粥样硬化性卒中的患者构成比(64.52％对29.63％;x2=29.456,P＜0.001)以及bb基因型(66.13％对37.04％;x2=17.422,P＜0.001)和b等位基因(75.00％对59.57％;x2=9.252,P=0.002)频率显著高于转归良好组;多变量logistic回归分析显示,bb基因型是缺血性卒中患者转归不良的独立危险因素(优势比3.842,95％可信区间1.782～8.283;P =0.001).结论 bb基因型可能是天津地区汉族人群缺血性卒中发病和转归不良的独立危险因素.     

Annexin A1: A new immunohistological marker of cholangiocarcinoma

AIM: To evaluate a new immunohistological marker, annexin A1 (ANXA1), in cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC). METHODS: Expression of ANXA1 protein was investigated in liver tissues from patients with CCA and HCC by immunohistochemistry. Its expression on differences stages of tumor development was investigated in hamster CCA tissues induced by Opisthorchis viverrini and N -nitrosodimethylamine. Moreover, mRNA expression of ANXA1 was assessed in CCA cell lines by quantitative real-time polymerase chain reaction and silencing of ANXA1 gene expression using small interfering RNA. RESULTS: In human CCA tissue arrays, immunohistochemical analysis revealed that the positive expression of ANXA1 was 94.1% (64/68 cases) consisting of a high expression (66.2%, 45/68 cases) and a low expression (33.8%, 23/68 cases). However, expression of ANXA1 protein was negative in all histologic patterns for HCC (46/46 cases) and healthy individuals (6/6 cases). In hamster with opisthorchiasis-associated CCA, the expression of ANXA1 was observed in the cytoplasm of inflammatory cells, bile duct epithelia and tumor cells. Grading scores of ANXA1 expression were significantly increased with tumor progression. In addition, mRNA expression of ANXA1 significantly increased in all of the various CCA cell lines tested compared to an immortalized human cholangiocyte cell line (MMNK1). Suppressing the ANXA1 gene significantly reduced the matrix metalloproteinase (MMP) 2 and MMP9, and transforming growth factor-β genes, but increased nuclear factor-kB gene expression. CONCLUSION: ANXA1 is highly expressed in CCA, but low in HCC, suggesting it may serve as a new immunohistochemical marker of CCA. ANXA1 may play a role in opisthorchiasis-associated cholangiocarcinogenesis.     

A new flea from Iran

Fleas are obligatory ectoparsites of humans and animals. These tiny insects are hematophagous and they can transmit a wide varity of disease agents to humans and domesticated animals. Indeed, this pest causes a considerable economic damages and health dangers particularly in tropical and subtropical. During an investigation on ectoparasites of five Mus muscuuls in Semnan province, Iran, 15 fleas (8 males and 7 females) were collected. The extracted fleas mounted using clearing, dehydrating, mounting process and preserved with Canada balsam. After precise study, all of examined specimens were recognized as Leptopsylla aethiopicus aethiopicus using available systematic keys. This is the first report of this genus and species in Iran. And this country is new locality for Leptopsylla aethiopicus aethiopicus.     

Coherence in the Ferroelectric A3ClO (A = Li,Na) Family of Electrolytes

Coherence is a major caveat in quantum computing. While phonons and electrons are weakly coupled in a glass, topological insulators strongly depend on the electron-phonon coupling. Knowledge of the electron−phonon interaction at conducting surfaces is relevant from a fundamental point of view as well as for various applications, such as two-dimensional and quasi-1D superconductivity in nanotechnology. Similarly, the electron−phonon interaction plays a relevant role in other transport properties e.g., thermoelectricity, low-dimensional systems as layered Bi and Sb chalcogenides, and quasi-crystalline materials. Glass-electrolyte ferroelectric energy storage cells exhibit self-charge and self-cycling related to topological superconductivity and electron-phonon coupling; phonon coherence is therefore important. By recurring to ab initio molecular dynamics, it was demonstrated the tendency of the Li₃ClO, Li_2.92Ba_0.04ClO, Na₃ClO, and Na_2.92Ba_0.04ClO ferroelectric-electrolytes to keep phonon oscillation coherence for a short lapse of time in ps. Double-well energy potentials were obtained while the electrolyte systems were thermostatted in a heat bath at a constant temperature. The latter occurrences indicate ferroelectric type behavior but do not justify the coherent self-oscillations observed in all types of cells containing these families of electrolytes and, therefore, an emergent type phenomenon where the full cell works as a feedback system allowing oscillations coherence must be realized. A comparison with amorphous SiO₂ was performed and the specific heats for the various species were calculated.     

A simple radiographic diagnosis of occult blow-out fractures

Standard radiographs of the orbit may not provide conclusive diagnosis of a blow-out fracture. Conventional and computed tomography have been employed effectively to resolve questionable cases. These imaging modalities generally are unavailable after hours and on weekends. The exaggerated Waters views are plain film radiographs easily and routinely obtainable that can demonstrate an occult fracture of the orbital floor.     

A priority dispatch system for emergency medical services

A decision tree priority dispatch system for emergency medical services (EMS) was developed and implemented in Atlanta and Fulton County, Georgia. The dispatch system shortened the average response time from 14.2 minutes to 10.4 minutes for the 30% of patients deemed most urgent (P less than or equal to .05); resulted in a significant increase in the use of advanced life support units for this group (P less than or equal to .02); decreased the number of calls that required a backup ambulance service; and significantly increased conformity to national EMS response time standards for critically ill and injured patients (P less than or equal to .0009). Due to dispatch error, 0.3% of calls were dispatched as least severe but subsequently were found to be most urgent.     

Co-administration of cyclosporine A alleviates thioacetamide-induced liver injury

AIM: To investigate the effects of cyclosporine A (CsA) on thioacetamide (TAA)-induced liver injury. METHODS: CsA was co-administrated (7.5 μg/kg body weight per day, i.p.) into rat to investigate the role of CsA on TAA-(200 mg/kg body weight per 3 d for 30 d, i.p.) induced liver injury. RESULTS: The data show that TAA caused liver fibrosis in rat after 30 d of treatment. CsA alleviates the morphological changes of TAA-induced fibrosis in rat liver. The blood glutamyl oxaloacetic transaminase (GOT)/glutamyl pyruvic transaminase (GPT) in the TAA-injury group is elevated compared to that of the normal rat. Compared with the TAA-injury group, the blood GOT/GPT and TGFβ1(by RT-PCR analysis) are reduced in the CsA plus TAA-treated rat. The level of the transforming growth factor receptor I (TGFβ-R1) in the CsA plus TAA-treated group shows higher than that in the TAA only group, but shows a lower level of the fibroblast growth factor receptor 4 (FGFR4) in the CsA plus TAA-treated group, when using the Western blot analysis. After immunostaining of the frozen section, TGFβ-R1 and FGFR4 are more concentrated in rat liver after CsA plus TAA injury. CONCLUSION: This result suggests that CsA has an alleviated effect on TAA-induced liver injury by increasing the multidrug resistance P-glycoprotein and could be through the regulation of TGFβ-R1 and FGFR4.     

A Call to Action to Enhance Filovirus Disease Outbreak Preparedness and Response

The frequency and magnitude of recognized and declared filovirus-disease outbreaks have increased in recent years, while pathogenic filoviruses are potentially ubiquitous throughout sub-Saharan Africa. Meanwhile, the efficiency and effectiveness of filovirus-disease outbreak preparedness and response efforts are currently limited by inherent challenges and persistent shortcomings. This paper delineates some of these challenges and shortcomings and provides a proposal for enhancing future filovirus-disease outbreak preparedness and response. The proposal serves as a call for prompt action by the organizations that comprise filovirus-disease outbreak response teams, namely, Ministries of Health of outbreak-prone countries, the World Health Organization, Médecins Sans Frontières, the Centers for Disease Control and Prevention—Atlanta, and others.     

Biosynthesis of the salinosporamide A polyketide synthase substrate chloroethylmalonyl-coenzyme A from S-adenosyl-l-methionine

Polyketides are among the major classes of bioactive natural products used to treat microbial infections, cancer, and other diseases. Here we describe a pathway to chloroethylmalonyl-CoA as a polyketide synthase building block in the biosynthesis of salinosporamide A, a marine microbial metabolite whose chlorine atom is crucial for potent proteasome inhibition and anticancer activity. S-adenosyl-l-methionine (SAM) is converted to 5′-chloro-5′-deoxyadenosine (5′-ClDA) in a reaction catalyzed by a SAM-dependent chlorinase as previously reported. By using a combination of gene deletions, biochemical analyses, and chemical complementation experiments with putative intermediates, we now provide evidence that 5′-ClDA is converted to chloroethylmalonyl-CoA in a 7-step route via the penultimate intermediate 4-chlorocrotonyl-CoA. Because halogenation often increases the bioactivity of drugs, the availability of a halogenated polyketide building block may be useful in molecular engineering approaches toward polyketide scaffolds.     

Oral manifestation in inflammatory bowel disease:A review

Inflammatory bowel diseases(IBDs),including Crohn’s disease(CD)and ulcerative colitis,not only affect the intestinal tract but also have an extraintestinal involvement within the oral cavity.These oral manifestations may assist in the diagnosis and the monitoring of disease activity,whilst ignoring them may lead to an inaccurate diagnosis and useless and expensive workups.Indurated tag-like lesions,cobblestoning,and mucogingivitis are the most common specific oral findings encountered in CD cases.Aphthous stomatitis and pyostomatitis vegetans are among non-specific oral manifestations of IBD.In differential diagnosis,side effects of drugs,infections,nutritional deficiencies,and other inflammatory conditions should also be considered.Treatment usually involves managing the underlying intestinal disease.In severe cases with local symptoms,topical and/or systemic steroids and immunosuppressive drugs might be used.     

Enteroscopy in small bowel Crohn’s disease: A review

Crohn’s disease (CD) is a chronic inflammatory condition of the gastrointestinal tract resulting in inflammation, stricturing and fistulae secondary to transmural inflammation. Diagnosis relies on clinical history, abnormal laboratory parameters, characteristic radiologic and endoscopic changes within the gastrointestinal tract and most importantly a supportive histology. The article is intended mainly for the general gastroenterologist and for other interested physicians. Management of small bowel CD has been suboptimal and limited due to the inaccessibility of the small bowel. Enteroscopy has had a significant renaissance recently, thereby extending the reach of the endoscopist, aiding diagnosis and enabling therapeutic interventions in the small bowel. Radiologic imaging is used as the first line modality to visualise the small bowel. If the clinical suspicion is high, wireless capsule endoscopy (WCE) is used to rule out superficial and early disease, despite the above investigations being normal. This is followed by push enteroscopy or device assisted enteroscopy (DAE) as is appropriate. This approach has been found to be the most cost effective and least invasive. DAE includes balloon-assisted enteroscopy, [double balloon enteroscopy (DBE), single balloon enteroscopy (SBE) and more recently spiral enteroscopy (SE)]. This review is not going to cover the various other indications of enteroscopy, radiological small bowel investigations nor WCE and limited only to enteroscopy in small bowel Crohn’s. These excluded topics already have comprehensive reviews. Evidence available from randomized controlled trials comparing the various modalities is limited and at best regarded as Grade C or D (based on expert opinion). The evidence suggests that all three DAE modalities have comparable insertion depths, diagnostic and therapeutic efficacies and complication rates, though most favour DBE due to higher rates of total enteroscopy. SE is quicker than DBE, but lower complete enteroscopy rates. SBE has quicker procedural times and is evolving but the least available DAE today. Larger prospective randomised controlled trial’s in the future could help us understand some unanswered areas including the role of BAE in small bowel screening and comparative studies between the main types of enteroscopy in small bowel CD.