Kinetics and enzyme involvement in the metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in microsomes of rat lung and nasal mucosa.

The rat lung and nasal cavity are two target organs for carcinogenesis by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In order to characterize further the enzymes involved in the bioactivation of NNK, detailed kinetic and inhibitory studies were conducted with rat lung and nasal mucosa microsomes, and the results were compared with previous studies. The enzymes in rat lung microsomes catalyzed the alpha-hydroxylation, pyridine N-oxidation and carbonyl reduction of NNK. The apparent Km for the formation of the NNK-derived keto aldehyde, NNK-N-oxide, the NNK-derived keto alcohol and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol were 28.8, 10.4, 7.0 and 178.1 microM respectively. In rat nasal microsomes, alpha-hydroxylation was the predominant pathway and the rate was approximately 200 times higher than that in lung microsomes. The apparent Kms for keto aldehyde and keto alcohol formation in rat nasal microsomes were 9.6 and 10.1 microM respectively. The cytochrome P450 inhibitors metyrapone and carbon monoxide markedly inhibited the metabolism of NNK in both rat lung and nasal microsomes. In rat lung microsomes, alpha-naphthoflavone and monospecific antibodies against P450s 1A2, 2A1 and 2B1 inhibited the formation of keto aldehyde by 39, 46, 64 and 23% respectively. In rat nasal microsomes, alpha-naphthoflavone and antibodies against P450s 1A2, 2A1 and 3A inhibited the metabolism of NNK by 80, 35, 20 and 14% respectively. The results indicate that cytochromes P450 play a major role in the metabolic activation of NNK in rat lung and nasal microsomes, and that there are tissue-related differences in NNK metabolism.     

Effects of thiamine deficiency on hepatic cytochromes P450 and drug-metabolizing enzyme activities

To elucidate the mechanisms by which thiamine deficiency affects hepatic microsomal monooxygenase activities, the effect of thiamine deficiency on two constitutive cytochrome P450 isozymes, P450IIE1 and P450IIC11, was investigated, using weanling male Sprague-Dawley rats. The clinical signs of thiamine deficiency were apparent after feeding a thiamine-deficient diet for 3 weeks. Thiamine deficiency caused an increase in P450IIE1, which was determined by N-nitrosodimethylamine demethylase assay and immunoquantitation of P450IIE1. This increase in the P450IIE1 level was mainly attributed to thiamine deficiency per se but not to dietary restriction. Ketone bodies were not elevated in thiamine-deficient rats, whereas ketone bodies were elevated and may have served as inducing factors in calorically restricted pair-fed animals. Injections of pyruvate or pyrithiamine in addition to thiamine deficiency did not potentiate the induction effect. On the other hand, thiamine deficiency did not affect the level of P450IIC11 during the 3 weeks of feeding the thiamine-deficient diet. In addition, thiamine deficiency increased cytosolic glutathione S-transferase activity but not steroid isomerase activity. The present study demonstrates the specificity of thiamine deficiency per se in the induction of P450IIE1 which does not involve an increase in the ketone body level.     

Thermafil热熔牙胶、Vitapex临床常用根管充填材料微渗漏比较研究

目的 :对比根充糊剂 牙胶尖、Vitapex 牙胶尖、Thermafil热熔牙胶三种根管充填材料对离体人牙根管的密封性能。方法 :将 5 0个新鲜拔除的人单根管牙 ,在釉牙骨质界处切除牙冠。将所有牙根随机分为 5组 ,每组 10个。 3个实验组分别用上述三种材料充填根管 ;剩余 2组 ,一组根管预备后不进行充填 ,另一组不进行根管预备 ,也不进行根管充填。用印度墨水染色法对比三种根管充填材料对离体人牙根管的密封性能 ,体视显微镜下测量染色线长度并进行统计学分析。结果 :根充糊剂 牙胶尖组、Vitapex 牙胶尖组和Thermafil热熔牙胶组的平均染色线长度分别为 3 .3 6± 0 .42mm、2 .0 9± 0 .19mm、1.0 5± 0 .3 7mm。Vitapex糊剂 牙胶尖或Thermafil热熔牙胶进行根管充填 ,产生的根管封闭性明显优于用根充糊剂 牙胶尖组根管充填 (P <0 .0 5 ) ;而Vitapex糊剂 牙胶尖和Thermafil热熔牙胶比较时 ,统计学无显著性差异 (P >0 .0 5 )。结论 :Thermafil热熔牙胶的密封性能最强 ,Vitapex糊剂 牙胶尖次之 ,根充糊剂 牙胶尖最弱。     

电刺激黑质对脑干伤害性单位放电的影响

本实验采用单细胞外记录神经元单位放电的方法，在Ｗｉｓｔａｒ大鼠上观察到网状巨细胞核。一区伤害性神经元５７个，其中伤害兴奋性神经元（ＮＥＮ）４２个，伤害抑制性神经元（ＮＩＮ）１５个。电刺激黑质对ＮＥＮ（２９）和ＮＩＮ（８的放电呈抑制作用，其反应百分率分别由刺激黑质第１分钟时的１．０±２．１％和－２０．４±６．２％，降到第５分钟时的－８３．６±１２．３％和－６５．４±１０．７％（Ｐ＜０．０１）。刺激黑质对少数ＮＥＮ（１３）和ＮＩＮ（７）的放电有兴奋作用，其值分别由第］分钟时的２０．５±７．３％和１．０±３．４％，升高到第５分钟时的７４．５±１０．７％和２１，５±８．６％（Ｐ＜０．０５）。氟哌啶醇注入ＰＡＧ腹外侧部可阻断刺激黑质的效应，这提示从黑质到网状巨细胞核α－区存在着一条痛调制通路，而且这种通路的递质是多巴胺能的。     

光动力学疗法与局部化疗联合治疗进展期食管贲门癌

作应用光动力学疗法（ＰＤＴ）对进展期食管贲门癌５５例进行治疗，并对其中１５例联合应用内镜下局部注射抗癌药物。对每一患均先静脉滴注血卟啉衍生物（ＨＰＤ）５ｍｇ／ｋｇ，于用药后２４，４８和７２ｈ分别用波长６３０ｎｍ的铜蒸汽激光照射肿瘤部位。联合治疗组除ＰＤＴ治疗外，于每次光照前肿瘤局部注射５－Ｆｕ２５０～５００ｍｇ。结果：联合治疗组的近期显效率高于单纯ＰＤＴ组（Ｐ〈０．０５）。病例随访６～１６月，     

2型糖尿病患者外周血白细胞iNOSmRNA表达的变化及意义

目的研究2型糖尿病DM患者外周血白细胞中iNOSmRNA表达的变化及其与糖尿病肾病DN发生、发展的关系。方法101例2型DM患者,根据尿微量白蛋白排泄率和血肌酐水平分为单纯DM组和不同的DN组,用原位杂交法检测外周血白细胞iNOSmRNA表达的阳性细胞的百分率,并与21例健康体检者进行比较。结果早期DN组白细胞iNOSmRNA表达的百分率明显高于对照组、DM组及晚期DN组(P<0.001)。结论外周血白细胞iNOSmRNA表达的变化参与了DN的发生、发展。     

阻塞性黄疸:PTC下胆管钳夹活检的技术方法学研究

目的探索切实可行的胆管病理学检查新途径.资料与方法连续92例阻塞性黄疸患者接受经皮肝穿刺胆管造影(PTC)和经皮肝穿胆管引流(PTCD)治疗.PTCD过程中,影像监测下经皮经肝胆管穿刺,向胆管内引入活检钳对梗阻段钳夹活检,行组织病理学检查.统计学分析用χ2检验或Fisher确切概率计算法,以α=0.05作为检验水准.结果 92例钳夹活检患者90例成功获得组织块,技术成功率97.83%(90/92).钳夹活检敏感性为88.04%,63例胆管癌性恶性肿瘤钳夹活检敏感性较25例非胆管癌性恶性肿瘤高(93.65%比72.00%,P＜0.05).结论PTC下胆管钳夹活检操作简单,创伤小,敏感性高,是一种值得推广的胆管病理学诊断新途径.     

免水分离超声乳化白内障摘除术临床观察

目的 :探讨免水分离术在超声乳化白内障摘除术中临床应用的有效性。方法 :随机选择白内障患者 2 0 0只眼 ,分两组。一组 (对照组 ) 95例 10 0只眼进行常规水分离术 ,二组 (观察组 ) 94例 10 0只眼 ,行免水分离术 ,所有患者均由同一医师进行超声乳化白内障摘除术联合人工晶体植入。临床观察超声乳化能量和时间 ,术后第一天、第三天、一周时视力 ,术中、术后并发症。结果 :( 1)平均超声能量Ⅰ、Ⅱ、Ⅲ、Ⅳ级核 ,一组分别是 :( 10 5 6± 4 16) %、 ( 17 88± 2 2 6) %、 ( 2 9 2 2± 3 5 4) %、 ( 3 7 88± 2 67) % ;二组分别是 ( 11 3 0± 1 89) %、 ( 18 76± 1 61) %、 ( 2 7 99± 3 5 8) %、 ( 3 9 2 2± 3 3 3 ) % ;两组平均超声能量差异无显著意义 (t =-0 5 12、 -1 496、 1 70 6、 -1 3 60 ,P =0 615、 0 14 2、 0 0 91、 0 182 ) ;平均超声时间一组分别为 ( 7 5 6±3 2 1)s、 ( 2 6 68± 5 15 )s、 ( 71 72± 17 2 2 )s、 ( 13 7 71± 3 8 60 )s ,二组分别为 ( 9 10± 1 2 0 )s、 ( 2 4 71± 4 0 9)s、 ( 76 17± 18 74)s、 ( 12 2 0 9± 3 5 14 )s ,两组平均超声时间差异无显著意义 (t =-1 42、 -1 415、 -1 3 69、 1 3 3 3 ,P =0 173、0 164、 0 174、 0 190 )。 ( 2 )术后一     

主动吸入药物烟对大鼠一氧化氮的影响

目的　探讨主动吸入药物烟对大鼠NO的影响。方法　制备大鼠主动吸烟模型 ,采用硝酸还原酶法测定各组大鼠血清、肺、心肌及脑组织的NO含量。结果　非药物烟组大鼠血清、肺、心肌及脑组织中NO含量明显低于非给烟对照组 ,药物烟高、中剂量组NO含量明显高于非药物烟组 ,接近非给烟对照组。结论　吸烟对大鼠血液、肺、心肌及脑组织有不同程度的损伤作用 ,使NO含量降低 ;药物烟具有一定的保护和防止NO含量降低的作用。     

单孔钻颅引流术治疗慢性硬膜下血肿80例临床分析

慢性硬膜下血肿（chronic subdural hematoma，CSDH）为受伤3W后出现硬膜下的血肿，是中老年患者轻微颅脑损伤后最为常见的颅内病变。约占颅内血肿的10％，起病隐匿，且临床表现无特征。虽然CSDH的治疗方法多种多样，但单孔钻颅闭式引流方法简单，操作容易，已成为神经外科医师普遍采用的方法。我们近3年来采用单孔钻颅闭式引流术治疗慢性硬膜下血肿80例，效果满意，现报告如下。