牛磺酸治疗支气管哮喘缓解期患者气道炎症的前瞻性研究

目的　观察牛磺酸对支气管哮喘缓解期患者气道炎症的治疗效果。方法　采用随机、对照、双盲、前瞻性研究方法 ,对 84例非急性发作期的轻、中度哮喘患者 ,从病情进入缓解期开始口服牛磺酸 (A组 )和安慰剂 (B组 ) ,疗程 1年 ,比较哮喘症状计分、治疗期间因哮喘复发或病情加重而住院的日数、每月使用沙丁胺醇的喷数、肺功能和气道反应性的变化以及血清中白细胞介素 5和白细胞介素 8的水平。结果　A组获得有效病例 32例 ,B组获得有效病例数 2 9例。A组患者治疗后的哮喘症状计分 (12 5± 4 8)分 /月、每月使用沙丁胺醇的喷数 (6 5± 2 9)次/月、治疗期间的住院日数 (1 2± 0 5 )d、FEV1(2 6± 0 5 )L与B组 (15 2± 5 1)分 /月 ;(9 8± 3 2 )次 /月 ;(3 3±0 9)d ;(2 2± 0 8)L差异显著 (P <0 0 5 ) ;两组患者的气道反应性无显著差异 ;血清中IL 5 [(16 3± 4 5 )ng/L]和IL 8[(15 8± 4 9) μg/L]的水平与B组 [(2 6 9± 12 7) μg/L ,(19 3± 5 2 ) μg/L]差异显著 (P <0 0 5 )。结论　牛磺酸能有效地改善支气管哮喘缓解期患者的临床症状和肺功能 ,抑制血清中炎症介质的释放 ,无明显的毒副作用 ,依从性良好 ,可能对哮喘缓解期气道炎症的治疗具有重要意义     

卡介菌多糖核酸联合特异性脱敏对支气管哮喘缓解期者气道反应性及血清IgE、IL-4的影响

目的观察卡介菌多糖核酸（BCG—PSN）联合特异性脱敏治疗（SIT）对支气管哮喘缓解期患者气道反应性的影响。方法 选择支气管哮喘缓解期患者70例，随机分为3组，分别给予BCG—PSN、SIT及BCG-PSN＋SIT（联合治疗组）治疗，并比较3组治疗后气道反应性、血清IgE及白细胞介素-4（IL-4）水平的变化。结果联合治疗组治疗2月后气道反应性改善值第1秒用力呼气量％改善值（△FEV1％）由（19．3±13．6）％增加至（23．6±18.2）％，至3月时明显增加至（32.7±18．8）％，此时血清总kE仅轻度升高[（317±363）kU／L]，IL-4水平显著降低[（7±9）ng／L]，与单用BCG—PSN和SIT组比较差异显著（P〈0.05或P〈0．01）。结论BCG—PSN与SIT联合治疗，可有效降低哮喘缓解期患者气道反应性，且减少体内炎性细胞因子释放。     

地塞米松对支气管哮喘豚鼠白介素4、白介素5及气道反应性的影响

目的 探讨地塞米松对支气管哮喘(简称哮喘)豚鼠模型白介素4(IL-4)、IL-5水平及气道高反应性(airway hyperreactivity,AHR)的影响,为激素治疗哮喘提供理论依据.方法 实验分为3组:正常对照组、哮喘模型组和地塞米松治疗组,每组各10只豚鼠.用卵白蛋白腹腔注射致敏和雾化吸入激发建立哮喘豚鼠模型,三通管做气管插管进行机械通气,测定气道内压力以反映气道反应性,酶联免疫吸附试验(ELISA)检测豚鼠血清中IL-4、IL-5含量.结果 哮喘模型组豚鼠血清IL-4、IL-5含量,分别为(38.2±3.4)ng/L和(344.4±21.8)ng/L,显著高于正常对照组,分别为(19.8±1.2)ng/L和(77.8±26.0)ng/L(P＜0.01);地塞米松组IL-4、IL-5含量,分别为(22.0±1.8) ng/L和(234.6±35.1)ng/L,均明显低于哮喘模型组(P＜0.01).哮喘豚鼠模型组气道反应性(0.013±0.014) g/L与正常对照组(0.168±0.186) g/L比较显著升高(P＜0.01);地塞米松组气道反应性(0.144±0.154) g/L与哮喘模型组比较显著降低(P＜0.01),与正常对照组比较差异无统计学意义(P＞0.05).结论 地塞米松能有效降低哮喘豚鼠AHR,其机制可能是抑制哮喘豚鼠体内IL-4、IL-5的生成.     

扎鲁司特片治疗113例支气管哮喘的临床应用

目的 评价白三烯受体拮抗剂扎鲁司特片治疗支气管哮喘的临床疗效及其安全性。方法 观察113例支气管哮喘患用药前、后哮喘自觉症状、肺功能指标、实验室指标及不良反应。结果 患治疗后第1、2、3、4周的平均晨间PEF值、平均夜间PEF值较前均有显性改变（P＜0.001）。患治疗后第2、4周FEV1值均较治疗前有显性改善（P＜0.0001）。治疗4周后，平均日间、夜间哮喘症状评分均减少明显，均 数的百分数增加明显。使用喘乐宁气雾剂喷数减少；5例患发生药物不良反应，发生率为4.42%；反应均较轻微。结论 白三受体拮抗剂扎鲁司特片能改善支气管哮喘患的肺功能、减轻哮喘症状，不良反应轻微，具有良好的临床疗效及安全性。     

扎鲁司特对运动性哮喘的作用

目的　研究白三烯受体拮抗剂 -扎鲁司特对运动性哮喘的治疗作用。方法　 2 8例运动性哮喘患者随机分为治疗组和对照组 ,在测定运动前和后基础 FEV1 和 FVC后分别给予扎鲁司特和安慰剂一周 ,观察其运动试验前和后的临床症状和肺功能变化。此外还测定了运动前后的尿白三烯值。结果　给药后治疗组运动试验转阴率 80 % (12 / 15 ) ,对照组运动试验转阴率 2 3% (3/ 13) ,二组转阴率相比 ,统计学有显著差异 P<0 .0 1)。尿白三烯 (u L TE4)运动前为 39.14± 34.5 5 pg/ μmol.Cr,运动后 2 h为 44 .5 5± 34.13pg/ μmol.Cr(P<0 .0 1)。结论　扎鲁司特对运动性哮喘患者具有明显的保护作用     

哮喘患儿血清Th1/Th2类细胞因子水平及其临床意义的研究

采用 IL ISA法测定了哮喘发作期和缓解期患儿的血清白介素 - 12 ( IL- 12 )和白介素 - 4 ( IL- 4 )。结果发现 ,发作期哮喘患儿 IL - 12水平 ( 3 5 .2± 11.18pg/ ml)显著低于缓解期 ( 4 2 .75± 13 .3 8pg/ ml)和健康儿 ( 4 5 .4 3±2 9.19pg/ ml) ,P分别 <0 .0 1、0 .0 5。发作期和缓解期哮喘患儿血清 IL - 4阳性率 (分别为 5 5 .5 6%和 3 6.3 6% )均显著高于健康儿 ( 9.1% ) ,P分别 <0 .0 1、0 .0 5。IL- 12和 IL- 4呈显著负相关 ( r=- 0 .3 4 ,P<0 .0 5 )。认为哮喘患儿存在明显的 Th1 / Th2 类细胞因子失衡 ,IL- 12和 IL- 4在哮喘发病中都起重要作用。吸入糖皮质激素等治疗可改变这种失衡状态。     

瘦素对支气管哮喘大鼠气道炎症及Th1/Th2细胞因子表达作用的影响

目的 探讨瘦素对支气管哮喘(简称哮喘)大鼠气道炎症和Th1/Th2细胞因子表达的影响.方法 应用随机数字表法将40只雌性SD大鼠随机分为正常体重对照组(A组)、正常体重哮喘组(B组)、正常体重瘦素干预组(C组)、肥胖对照组(D组)和肥胖哮喘组(E组),建立大鼠肥胖和哮喘模型.测定气道反应性,计数BALF中白细胞总数、嗜酸粒细胞及中性粒细胞数目,ELISA法测定血清和BALF中白细胞介素(IL)-4、γ-干扰素(IFN-γ)及瘦素浓度,Western blot及逆转录PCR法测定肺组织瘦素蛋白及mRNA的表达.结果 C、E组大鼠以10、100、300 ug/kg浓度乙酰胆碱尾静脉注射后气道阻力[分别为(0.89±0.11)、(1.02±0.10)、(1.13±0.11)cm H2O·ml-1·s-1(1 cm H2O=0.098 kPa)和(0.95±0.10)、(1.12±0.10)、(1.14±0.10)cm H2O·ml-1·s-1],明显高于B组[分别为(0.64±0.13)、(0.74±0.07)、(0.77±0.09)cm H2O·ml-1·s-1],均P<0.05.C、E组BALF中白细胞总数[分别为(91±9)×104/ml和(108±21)×104/ml],中性粒细胞计数[分别为(12.4±4.0)×104/ml和(14.2±5.9)×104/ml]均高于B组[分别为(79±7)×104/ml和(2.4±1.1)×104/ml],均P<0.05.C、E组血清及BALF中IFN-γ浓度[分别为(42.3±3.5)、(45.1±4.8)、(19.2±1.8)和(20.3±1.5)ng/L]明显高于B组[分别为(16.5±1.4)和(9.3±1.0)ng/L],均P<0.05.C、E组肺组织瘦素蛋白及mRNA表达[分别为(0.40±0.07)、(0.44±0.05)ng/L和(0.34±0.06)、(0.38±0.04)ng/L]均明显高于B组[(0.31±0.03)ng/L和(0.21±0.04)ng/L],均P<0.05.结论 瘦素可促进哮喘气道炎症,并以中性粒细胞浸润和Th1型炎症反应增强为特点.     

卡介菌多糖核酸对支气管哮喘小鼠气道反应性及气道炎症的影响

目的 探讨卡介菌多糖核酸对哮喘小鼠气道反应性及气道炎症的影响.方法 选择Balb/c小鼠,以卵白蛋白致敏激发建立小鼠哮喘模型,设立卡介菌多糖核酸组、正常组、哮喘组.卡介菌多糖核酸按剂量具体分为1 μg,10 μg,100 μg亚组,均在第一次抗原致敏前7 d腹腔注射给药.末次激发后48 h采用美国Buxco公司小鼠整体体积扫描记法测定气道反应性,以乙酰甲胆碱各浓度激发时增强的呼吸间歇(Enhanced Pause,Penh)表示.以PC100[气道反应性升高为生理盐水(NS)值2倍时的Mch激发浓度]及Penh/NS%max综合评价气道反应性.收集支气管肺泡灌洗液,涂片后苏木素-伊红染色计数嗜酸粒细胞比例,肺组织病理检测.结果 1μg肛组PC100(13.2±6.9)g/L、10/μg组(11.8±5.58)g/L与哮喘组(5.97±1.73)g/L相比,P<0.01表示差异有统计学意义;1 μg、10 μg组Penh/NS%max分别为(623.22±252.39)%,(519.71±200.41)%,显著低于哮喘组(1 306.83±540.46)%,P<0.01.10 μg组BALF嗜酸粒细胞百分比为(42.75±7.44)%显著低于哮喘组(57.25±13.2)%,P<0.01,1 μg组、100 μg组BALF嗜酸粒细胞百分比与哮喘组相比,差异无统计学意义.结论 卡介菌多糖核酸可以显著抑制哮喘小鼠的气道高反应性及气道炎症.     

川芎嗪对大鼠支气管哮喘模型气道重塑的影响及机制

目的　观察川芎嗪对支气管哮喘 (简称哮喘 )大鼠模型气道重塑的抑制作用并探讨其作用机制。方法　 32只SD大鼠按随机数字表法分成正常对照组 (A组 )、哮喘模型组 (B组 )、小剂量川芎嗪组 (C组 ,4 0mg/kg)和大剂量川芎嗪组 (D组 ,80mg/kg) ,以卵白蛋白 (OVA)致敏并长期吸入激发制备大鼠慢性哮喘模型。采用免疫组化半定量法测定气道壁胶原和转化生长因子 β1(TGF β1)含量 ,同时测定气道内、外径及平滑肌层、网状基底膜的厚度。结果　D组气道平滑肌层、网状基底膜的厚度为 (11 3± 1 3) μm、(11 3± 1 7) μm ,B组分别为 (19 7± 1 8) μm、(19 8± 1 6 ) μm ,两组比较差异有统计学意义 (P均 <0 0 1) ,但D组与A组 [(10 6± 1 2 ) μm、(9 8± 1 6 ) μm]、C组 [(11 6± 0 9) μm、(12 3± 1 8) μm]比较差异无统计学意义 (P均 >0 0 5 ) ;D组气道内外径比值为 0 77± 0 0 6 ,B组为0 6 3± 0 0 5 ,D组与B组比较差异有统计学意义 (P <0 0 1) ;D组气道壁Ⅲ型胶原及TGF β1含量吸光度 (A)值分别为 2 1± 5、2 6± 5 ,B组分别为 5 5± 7、6 9± 14 ,两组比较差异有统计学意义 (P <0 0 1) ,D组与C组 (32± 8、38± 10 )比较差异有统计学意义 (P <0 0 5 ) ,C组与B组比较差异也有统计学意义 (P <0 0     

钙池操纵性钙通道抑制剂SKF96365对慢性哮喘小鼠气道重塑和气道高反应性的作用

目的:观察钙池操纵性钙通道抑制剂SKF96365对小鼠慢性哮喘模型气道重塑和气道高反应性的影响。方法:用鸡卵清白蛋白(OVA)致敏和激发小鼠,建立慢性哮喘模型,33只雌性BALB/c小鼠随机分为3组:对照组、哮喘组、SKF96365组,每组11只,其中SKF96365组于每次激发前30 min给予SKF96365(10mg/kg)干预。哮喘组和SKF96365组于第0、7、14 d腹腔注射(i.p)200μL致敏液(含OVA粉剂20μg、氢氧化铝凝胶2 mg);自第21天起,腹腔注射1%戊巴比妥钠(70mg戊巴比妥钠/kg小鼠体重)麻醉小鼠后,OVA(40μg)滴鼻(i.n),连续6周,每周3次,共18次。对照组则在相同时间给予相应剂量的生理盐水腹腔注射和滴鼻。最后一次激发后24 h,各组分别随机取5只小鼠用于检测组织病理学变化,另6只小鼠采用Buxco小动物肺功能仪检测气道高反应性。其中组织病理学检测计算杯状细胞(过碘酸希夫染色阳性,PAS+)、胶原细胞(Masson阳性)和平滑肌细胞(α-SMA阳性)阳染面积/支气管基底膜周长值来评估小鼠气道重塑;观察给予不同浓度乙酰甲胆碱雾化时的气道阻力(resistance index,RI)最大值,评估小鼠气道高反应性。结果:对照组未见PAS阳性染色区域,哮喘组和SKF96365组杯状细胞增生高于对照组(7.29±2.04,4.49±1.70 vs 0.00±0.00,均P0.01),且SKF96365组低于哮喘组(P0.05)。Masson染色显示哮喘组和SKF96365组上皮下胶原沉积高于对照组(9.23±1.41,7.30±1.33 vs 1.60±0.77,均P0.01),且SKF96365组低于哮喘组(P0.05)。α-SMA免疫组化显示哮喘组和SKF96365组平滑肌增生肥大高于对照组(4.54±1.05,3.15±0.57 vs 1.97±0.69,均P0.05),且SKF96365组低于哮喘组(P0.05)。当乙酰甲胆碱(Mch)≤6.25 mg/m L时,3组小鼠气道阻力无显著差异(P0.05),当25 mg/m LMch≥12.25 mg/m L时,哮喘组小鼠气道阻力明显大于对照组小鼠(P0.001),当Mch≥25 mg/m L时,哮喘组小鼠气道阻力大于SKF96365组(P0.05)。结论:采用SKF96365干预后,慢性哮喘小鼠气道重塑和气道高反应性指标均有改善,提示SKF96365可能对哮喘气道重塑和气道高反应性具有抑制作用。     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.