食管结核误诊为食管癌临床分析

目的分析食管结核的临床特点、误诊原因及防范措施。方法回顾性分析误诊为食管癌的食管结核2例的临床资料。结果1例因吞咽困难2个月,进行性加重伴持续性胸骨后疼痛1月余就诊,院外多次行胃镜及病理检查均提示食管癌可能性大,入院后经胃镜、病理检查及实验室检查结果确诊食管结核,给予三联抗结核治疗,症状明显好转。1例因进行性吞咽困难伴乏力、消瘦5个月就诊,两次胃镜及活检均考虑食管癌,择期行手术治疗,术后病理检查提示食管结核,给予三联抗结核治疗,病情明显好转。结论食管结核临床少见,部分患者无结核中毒症状,且临床表现无特异性,极易误诊为食管癌,提示临床应加强对本病的认识,多次多部位行病理检查,必要时行诊断性抗结核治疗,可一定程度避免误诊的发生。     

Association of slow N-acetyltransferase 2 profile and anti-TB drug-induced hepatotoxicity in patients from Southern Brazil

Purpose  To determine the frequency of N-acetyltransferase 2 (NAT2) polymorphisms, the NAT2 acetylation profile and its relation to the incidence of gastrointestinal adverse drug reactions (ADRs), anti-tuberculosis (TB) drug-induced hepatotoxicity, and the clinical risk factors for hepatotoxicity in a population from Brazil. Methods  Two hundred and fifty-four Brazilian TB patients using isoniazid (INH), rifampicin (RMP), and pirazinamide (PZA) were tested in a prospective cohort study. NAT2 genotyping was performed by direct PCR sequencing. The association between gastrointestinal ADRs/hepatotoxicity and the NAT2 profile genotype was evaluated by univariate analysis and multiple logistic regression. Results  Of the 254 patients analyzed, 69 (27.2%) were slow acetylators and 185 (72.8%) were fast acetylators. Sixty-five (25.6%) patients were human immunodeficiency virus (HIV)-positive. Thirty-three (13%) and 14 (5.5%) patients developed gastrointestinal ADR and hepatotoxicity, respectively. Of the 14 hepatotoxicity patients, nine (64.3%) were slow acetylators and five (35.7%) were fast acetylators. Sex, age, presence of hepatitis C virus, alcohol abuse, and baseline aminotransferases were not found to be risk factors for hepatotoxicity. However, logistic regression analysis revealed that slow acetylator status and the presence of HIV (p < 0.05) were independent risk factors for hepatotoxicity. Conclusions  Our findings show that HIV-positive patients that have the slow acetylation profile are significantly associated with a higher risk of developing hepatotoxicity due to anti-TB drugs. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

鞘内注射异烟肼联合地塞米松治疗结核性脊膜脊髓炎的价值

目的:探讨鞘内注射异烟肼联合地塞米松治疗结核性脊膜脊髓炎的临床价值.方法:选择结核性脊膜脊髓炎患者80例,分为两组,各40例,对照组实施异烟肼1200mg/d、链霉素600mg/d、利福平1g/d肌内注射,地塞米松10mg/d静脉注射,观察组则将异烟肼与地塞米松改为鞘内注射,连续治疗8周为1疗程,对所有患者随访20周,比较治疗前后两组脑脊液常规与生化结果,统计两组脑脊液细胞、蛋白、氯化物及糖恢复正常时间及治疗期间发生的不良反应.结果:治疗后两组,脊液中糖、蛋白、氯化物水平及细胞总数均显著低于治疗前(P＜0.05),观察组脊液中糖、蛋白、氯化物水平及细胞总数均低于对照组(P＜0.05),观察组脑脊液细胞、蛋白、氯化物及糖恢复正常时间均显著快于对照组(P＜0.05),观察组发生腰疼、背痛,低颅压性头痛及肝功能损伤的比例显著低于对照组(P＜0.05).结论:鞘内给予异烟肼联合地塞米松能有效提高脑脊液内药物浓度,提高药物治疗效果,缩短化疗时间,减少全身用药的不良反应.     

HPLC法测定异福胶囊中异烟肼和利福平的含量

目的：建立异福胶囊中同时测定异烟肼和利福平的含量的方法。方法采用HPLC梯度洗脱法,色谱柱为十八烷基硅烷键合硅胶为填充柱（Agilent ZORBAX Eclipse XDB－C18,4．6mm ×250mm,5μm）,流动相分别为流动相A：甲醇－0．015mol? L －1磷酸二氢钠溶液（用磷酸调节pH值为6．5）（5∶95）,流动相B：甲醇－0．015mol? L－1磷酸二氢钠溶液（用磷酸调节pH值为6．5）（62∶38）;流速：1．3mL? min －1,检测波长：262nm。结果以峰面积（y）对进样浓度（x）线性回归,异烟肼回归方程：y＝29773x－7020．2,r＝0．9998,线性范围为11．48～183．6μg? mL －1;利福平回归方程：y＝35061x－67601,r＝0．9997,线性范围为13．78～275．6μg? mL －1,峰面积与浓度呈良好的线性关系。异烟肼和利福平加样回收率分别为：分别为100．1％和99．9％（n＝9）,RSD分别为O．23％和0．26％。结论本方法操作简便、准确、重现性好,可用于同时测定异福胶囊中异烟肼和利福平的含量。     

反相高效液相色谱法同时测定复方利福平胶囊中异烟肼、利福平的含量

应用反相高效液相色谱法,采用５μｍＨｙｐｅｂｓｉｌＯＤＳ色谱柱,以０．１ｍｏｌ／Ｌ磷酸二氢钠溶液：甲醇（４０：６０）为流动相,检测波长２６８ｎｍ,建立了同时测定复方利福平胶囊中异烟肼、利福平的含量测定法。采用外标对照法测定,方法平均回收率在９９．００％,以上,相对标准差小于１．０％,结果令人满意。     

异福片的药物动力学与相对生物利用度

目的　研究两种异福片的药物动力学 ,并评价两者的生物等效性。方法　采用RP -HPLC测定 2 4名志愿受试者单剂量po异福片供试品与参比品后利福平和异烟肼血药浓度的变化 ,用 3p97药动学程序拟合药动学参数。结果　两种制剂中利福平AUC0→t分别是 16 3 6 6± 11.33μg·h·ml-1与 172 5 9± 76 .31μg·h ml-1,Tmax分别为 1.92± 0 .19h与 1.96± 0 .4 5h ,Cmax分别是 2 6 .4 2± 11.97μg·ml-1与 2 6 .18± 11.5 7μg·ml-1。两种制剂中异烟肼AUC0→t分别是 4 4 .2 6± 18.84 μg·h·ml-1与 4 6 .18± 16 .6 0μg·h·ml-1,Tmax分别为 1.83± 0 .33h和 1.88± 0 .31h ,Cmax分别是 7.73± 3.2 2 μg·ml-1与 7.76± 3.0 0 μg·ml-1。经剂量校正 ,两种制剂中两组份的lnAUC0→∞ 、lnAUC0→t、Cmax经方差分析均无显著性差异 (P >0 .0 5 ) ;Tmax用双单侧t检验进行生物等效性评价 ,无显著性差异 (P >0 .0 5 )。结论　两种制剂为生物等效制剂 ,异福片供试品中利福平和异烟肼的相对生物利用度分别为95 .86 %± 11.86 %和 95 .5 4 %± 12 .5 3%。     

Amelioration of hepatotoxicity by biocleavable aminothiol chimeras of isoniazid: Design,synthesis, kinetics and pharmacological evaluation

AIM To overcome the hazardous effects on liver caused by long-term use of antitubercular agent isoniazid(INH) by developing a novel hepatoprotective prodrug strategy by conjugating INH with aminothiols as antioxidant promoities for probable synergistic effect.METHODS INH was conjugated with N-acetyl cysteine(NAC) and N-(2)-mercaptopropionyl glycine using the SchottenBaumann reaction and with L-methionine using Boc-anhydride through a biocleavable amide linkage. Synthesized prodrugs were characterized by spectral analysis, and in vitro and in vivo release studies were carried out using HPLC. Their hepatoprotective potential was evaluated in male Wistar rats by performing liver function tests, measuring markers of oxidative stress and carrying out histopathology studies.RESULTS Prodrugs were found to be stable in acidic(pH 1.2) and basic(pH 7.4) buffers and in rat stomach homogenates, whereas they were hydrolysed significantly(59.43%-94.93%) in intestinal homogenates over a period of 6 h. Upon oral administration of prodrug NI to rats, 52.4%-61.3% INH and 47.4%-56.8% of NAC were recovered in blood in 8-10 h. Urine and faeces samples pooled over a period of 24 h exhibited 1.3%-2.5% and 0.94%-0.9% of NAC, respectively, without any presence of intact NI or INH. Prodrugs were biologically evaluated for hepatoprotective activity. All the prodrugs were effective in abating oxidative stress and re-establishing the normal hepatic physiology. The effect of prodrug of INH with NAC in restoring the levels of the enzymes superoxide dismutase and glutathione peroxidase and abrogating liver damage was noteworthy especially. CONCLUSION The findings of this investigation demonstrated that the reported prodrugs can add safety and efficacy to future clinical protocols of tuberculosis treatment.     

Antibacterial activity of selected Cameroonian dietary spices ethno-medically used against strains of Mycobacterium tuberculosis

Ethnopharmacological relevance

Tuberculosis (TB) is considered as a re-emerging disease and one of the most important public health problems worldwide. The use or (in most cases) misuse of existint anti-tuberculosis drugs over the years has led to an increasing prevalence of resistant strains, establishing an urgent need to search for new effective agents. Spices are largely used ethno-medically across Africa.

Aim of the study

The present study aimed to evaluate the in vitro antimycobacterial activities of a total of 20 methanol crude extracts prepared from 20 Cameroonian dietary spices for their ability to inhibit the growth of or kill Mycobacterium tuberculosis strains H₃₇Rv (ATCC 27294) and H₃₇Ra (ATCC 25177).

Materials and methods

The antituberculosis screening was performed using the Microplate Alamar Blue Assay (MABA) method to determine the minimum inhibitory concentration (MIC) and the minimum mycobactericidal concentration (MBC).

Results

Fifteen (15) plant extracts out of 20 showed varied levels of antimycobacterial activity against the strains M. tuberculosis H₃₇Rv and H₃₇Ra, with MICs in the range of 2.048–0.016 mg/ml. The extract of Echinops giganteus exhibited the most significant activity with a MIC value of 32 μg/ml and 16 μg/ml, respectively against H₃₇Ra and H₃₇Rv. To the best of our knowledge, the antimycobacterial activity of the tested spices has not been reported before and therefore our results can be evaluated as the first report about the antimycobacterial properties.

Conclusions

The results of this study suggest that Echinops giganteus and Piper guineense could be important sources of bactericidal compounds against M. tuberculosis and could probably be promising candidates that can be further investigated.     

肺结核丸治疗难治性肺结核随机对照临床研究

[目的]探讨肺结核丸治疗难治性肺结核的临床效果。[方法]将我院收治的60例难治性肺结核患者,随机分为对照组和治疗组,对照组采用异烟肼联合利福平治疗,治疗组肺结核丸治疗。分析两组治疗效果及不良反应发生情况。[结果]治疗组总有效率与对照组相比,差异无统计学意义(P>0.05)。治疗组显效率显著高于对照组,差异有统计学意义(P<0.05)。治疗组病灶吸收率显著高于对照组,差异有统计学意义(P<0.05)。[结论]采用肺结核丸治疗难治性肺结核,疗效优于利福平联合异烟肼治疗,病灶恢复良好,使用方便,值得临床推广应用。     

应用基因芯片方法检测结核分枝杆菌利福平和异烟肼的耐药性

目的 应用基因芯片方法检测结核分枝杆菌(Mycobacterium tuberculosis,Mtb)对利福平和异烟肼的耐受性,评价其临床应用价值。方法 应用聚合酶链反应（polymerase chain reaction,PCR）扩增-基因芯片杂交的方法检测经常规药敏实验证实的30株Mtb利福平和异烟肼敏感株和50株耐利福平和异烟肼分离株的rpoB基因及katG和inhA基因突变,同时以PCR-直接测序法为对照。结果 应用PCR-基因芯片与基因测序方法检测30株Mtb利福平敏感株rpoB基因和异烟肼敏感株katG基因和inhA基因均为野生型。50株Mtb利福平耐药株中,PCR-基因芯片与基因测序分析3株rpoB基因均为野生型,41株均为突变型;6株PCR-基因芯片与基因测序结果不一致。50株Mtb异烟肼耐药株中,PCR-基因芯片与基因测序分析16株katG基因和30株inhA基因均为野生型,31株katG基因均为315位密码子突变,7株inhA基因均为15位突变型,其中2株为katG和inhA双重突变;3株katG和13株inhA PCR-基因芯片与基因测序结果不一致。结论 应用PCR-基因芯片方法可快速、有效地检出大多数Mtb耐多药分离株,指导临床用药。