大蒜素治疗大鼠卡氏肺孢子虫肺炎的研究

目的　研究大蒜素对大鼠卡氏肺孢子虫肺炎(PCP)的治疗效果。　方法　地塞米松连续肌肉注射Wistar大鼠8周,建立大鼠PCP动物模型。用大蒜素治疗实验大鼠,同时设复方新诺明治疗对照组和PCP模型空白对照组。通过各组大鼠肺重、肺重/体重比值、肺印片中每100个油镜视野肺孢子虫包囊均数等指标考核疗效。　结果　大蒜素治疗组大鼠平均肺重为1.73±0.17、肺重/体重比值为0.84±0.12,显著低于PCP模型对照组的 2.31±0.35、1.25±0.35(P<0.01)。肺印片中包虫数较PCP模型对照组减少62.9% ,其与复方新诺明治疗对照组接近。　结论　大蒜素对实验大鼠卡氏肺孢子虫肺炎有明显的治疗作用,治疗效果接近复方新诺明。     

用PCR诊断不同虫荷量的大鼠卡氏肺孢子虫肺炎的价值

目的　评价在不同虫荷量条件下用 PCR诊断大鼠卡氏肺孢子虫肺炎 (PCP)的价值。　方法　将 PCP大鼠随机分为药物治疗组及未治疗组 ,测定其肺虫荷量 ,收集其支气管灌洗液 (BAL F)和血清标本 ,用 PCR和半套式 (Sn) PCR检测标本中的卡氏肺孢子虫基因 ,比较 PCR和环六亚甲基四胺银 (GMS)染色结果 ,及与病鼠肺虫荷量的关系。　结果　虫荷量高的未治疗组病鼠的 BAL F标本 PCR、Sn PCR及 GMS染色阳性率分别为 10 0 %、10 0 %和 92 .6 % ,差异无显著性 (P>0 .0 5 ) ;而虫荷量低的治疗组的 PCR(88.1% )、Sn PCR(94 .9% )阳性率均显著高于 GMS染色镜检阳性率 (30 .5 % ) (P<0 .0 5 )。肺虫荷量 >5 0 0个 /mg肺的 PCP大鼠 ,血清 PCR阳性率显著高于≤ 5 0 0者 (分别为 4 2 .9%和 1.7% )。　结论　PCR可用于虫株负荷量较低时的 PCP诊断 ,对判断 PCP病情及疗效考核亦有一定的帮助。     

感染卡氏肺孢子虫大鼠血清中可溶性细胞黏附分子-1（sICAM-1）变化的研究

目的 检测卡氏肺孢子虫肺炎(PCP)大鼠血清中可溶性细胞黏附分子-1（sICAM-1）水平, 以及经复方磺胺甲噁唑（TMP-SMZ）治疗后对sICAM-1含量的影响。 方法 纯系Wistar大鼠50只, 随机分为 PCP模型组（P组18只）、TMP?鄄SMZ治疗组（S组18只）及正常对照组（N组14只）。P组及S组于大鼠后腿肌肉注射地塞米松（1 mg/只，每周2次、间隔3 d），诱导建立PCP大鼠模型。N组同法注射生理盐水。镜检确认PCP诱导成功后，S组从第3周起灌胃TMP-SMZ[每天1次, 250 mg/（kg·d）］，5 d为1 疗程，间隔2周，共3个疗程。分别于第0、3、6、9及12周取血, 检测血清中sICAM-1水平，观察肺脏、肝脏病理及病原学变化。 结果 血清sICAM-1水平，P组第3周的(1.847±0.50)ng/ml显著低于第0周的（2.407±0.81) ng/ml(P<0.05)； S组第3周的(1.787±0.59) ng/ml显著低于第0周的（2.478±0.59) ng/ml(P<0.01), 以后逐渐上升。P组第9周的（3.233±0.83) ng/ml、 12周（3.984±0.87) ng/ml显著高于第0周的（2.407±0.81) ng/ml(分别为P<0.05, P<0.01)； S组第12周的（3.621±1.62) ng/ml显著高于第0周的（2.478±0.59) ng/ml(P<0.05)。P组与S组第9、12周[分别为(2.697±0.78) ng/ml及(3.621±1.62) ng/ml] 均显著高于N组(分别为P<0.05、P<0.01)。S组与P组间差异无统计学意义(P>0.05)。 结论 大鼠血清中sICAM-1含量较低，但在诱导PCP后其含量显著增高。     

肺孢子虫肺炎大鼠支气管肺泡灌洗液酶含量变化及大蒜素治疗对其影响

目的 研究卡氏肺孢子虫肺炎(PCP)大鼠支气管肺泡灌洗液(BALF)酶含量变化以及大蒜素治疗对其影响。 方法 用地塞米松连续肌肉注射Wistar大鼠， 诱导建立PCP大鼠模型。诱导第3、6、9周分别于后腿肌肉深部注射大蒜素治疗（10 mg/kg， 1次/d， 连续5 d）。同时设甲氧苄氨嘧啶(TMP)?鄄磺胺甲基异噁唑(SMZ)治疗对照组(SMZ/TMP组)、 PCP模型对照组和空白对照组。 于最后1次治疗3 d后处死大鼠， 无菌收集BALF， 测定谷草转氨酶(AST)、 谷丙转氨酶(ALT)、 胆碱脂酶(CHE)、 碱性磷酸酶(ALP)、 乳酸脱氢酶(LDH)、 肌酸激酶(CK)及其同工酶(CKMB)、 a?鄄羟丁酸脱氢酶(HBDH)、 a?鄄L?鄄岩藻糖甘酶(AFU)、 5′-核苷酸酶(5′NT)及腺苷脱氨酶(ADA)含量。 结果 PCP模型组ALP含量［（573.41 ± 350.63） U/L］显著高于空白对照组［（210.56 ± 114.41） U/L］（q=4.682， P<0.01）、 大蒜素治疗组［（392.07 ± 217.57） U/L］（q=3.851， P<0.05）以及SMZ/TMP组［（325.21 ± 180.65） U/L］（q=4.380， P<0.01）。 CK、 CKMB及5′NT含量， PCP模型对照组［依次为948.94 ± 403.43、 489.47 ± 254.46及（6.76 ± 3.11） U/L］显著高于空白对照组［426.22 ± 319.00、 213.33 ± 144.54及（3.22 ± 1.20） U/L］（q=4.696， 3.784， 3.812， P<0.05）。AST、 ALT、 CHE、 LDH、 HBDH、 AFU及ADA含量， 4组之间差异均无统计学意义(F=1.852， 0.958， 2.470， 1.423， 1.178， 1.342， 0.611， P>0.05)。 结论 PCP大鼠BALF中ALP、 CK、 CKMB及5′NT含量显著升高, 大蒜素治疗可使ALP含量显著降低。     

结核分枝杆菌DNA疫苗对小鼠结核病免疫治疗作用的实验研究

目的探讨结核分枝杆菌DNA疫苗pcD85B、pcDMPT64以及小鼠白细胞介素12(IL-12)真核表达质粒psIL12对结核分枝杆菌感染的疗效与机制。方法将结核分枝杆菌H37Rv感染的C57BL/J6小鼠100只随机分成生理盐水对照组、pcDNA3.1对照组,psIL12治疗组,pcD85B、pcDMPT64、pcD85B+pcDMPT64、pcD85B+psIL12DNA疫苗治疗组。感染4周后分别给予生理盐水、空质粒、psIL-12及DNA疫苗,第1次治疗后2个月处死小鼠,检测器官荷菌量、脾淋巴细胞特异性γ干扰素(IFN-γ)、白细胞介素4(IL4)、肿瘤坏死因子-α(TNF-α)的分泌水平,并于第1次治疗后2个月、5个月观察小鼠肺、脾组织病理改变情况。结果pcD85B治疗组肺组织荷菌量(lg-1CFU/g)为6.99±0.40,比生理盐水对照组(8.15±0.37)、pCDNA3.1对照组(8.19±0.29)显著降低(P<0.01);脾组织荷菌量(lg-1CFU/g,x±s)为5.17±0.33,比生理盐水对照组(5.76±0.16)及空质粒对照组(5.88±0.21)显著降低(P<0.05)。psIL12治疗组的肺(7.41±0.50)、脾(5.31±0.21)荷菌量比对照组显著降低(P<0.05);pcD85B+psIL12治疗组肺、脾荷菌量与pcD85B组比较差别无统计学意义。pcD85B组脾淋巴细胞IFN-γ、TNFα水平比对照组显著升高(P<0.05),各组间IL4水平差异无统计学意义。生理盐水对照组、pCDNA3.1对照组肺组织     

加味补中益气汤对肺孢子虫肺炎大鼠的免疫调节作用研究

目的探讨加味补中益气汤对大鼠肺孢子虫肺炎(PCP)的免疫调节机制及抑制虫体生长的作用。方法建立大鼠PCP动物模型并分成4组,分别用中药预防、中药治疗、TMP-SMZ治疗,PCP模型对照组不治疗。健康对照组不感染、不治疗。8周末处死大鼠,制肺印片,观察每视野虫体包囊数,并采用酶联免疫吸附法检测大鼠血清中肿瘤坏死因子(TNF-α)和白介素-2(IL-2)水平。结果中药预防组和治疗组及TMP-SMZ治疗组,PCP大鼠肺组织虫体包囊数分别为18.45±6.77、20.68±6.48和23.24±10.33,模型对照组为65.36±15.45,差异有统计学意义(P<0.05);血清中TNF-α和IL-2含量分别为22.39±7.01和24.2±6.07、18.02±3.36和15.67±5.39、16.76±3.98和17.11±6.46、8.92±2.59和8.84±3.17,差异有统计学意义(P<0.05)。结论加味补中益气汤对PCP大鼠具有较好的免疫调节作用,从而抑制肺孢子虫生长。     

阿托伐他汀钙对肾血管性高血压大鼠模型左室重构的影响

目的观察阿托伐他汀钙对肾血管性高血压大鼠左室重构的保护作用。方法应用经典的两肾一夹方法,制备肾血管性高血压大鼠模型。实验动物随机分对照组(假手术)、高血压组及治疗组,每组各7只。治疗组给予阿托伐他汀钙(立普妥2 mg/kg)治疗6周。采用鼠尾测压法测定大鼠血压的变化;放射免疫分析法测定大鼠血浆血管紧张素(Ang)Ⅱ含量和肾素活性;称量法计算各组大鼠心脏重量及左室重量与体重比值。结果高血压大鼠血浆AngⅡ含量和肾素活性分别为(106.4±7.8)ng/L和(20.6±2.4)ng/L,比对照组〔(72.3±5.4)ng/L和(12.5±3.7)ng/L〕明显增高(P<0.01);心脏重量为(1.46±0.09)g,左室重量与体重比值为(3.54±0.19)×10-3,比对照组〔(0.98±0.07)g和(2.28±0.06)×10-3〕显著增大(P<0.01)。给予小剂量阿托伐他汀钙治疗6周后,AngⅡ含量〔(68.3±6.9)ng/L〕和肾素活性〔(8.7±2.3)ng/L〕明显下降(P<0.01),心脏重量减至(1.05±0.04)g,左室重量与体重比值降至(2.36±0.07)×10-3,与对照组比较差异无统计学意义(P>0.05)。结论阿托伐他汀钙能明显降低高血压大鼠心脏重量及左室重量与体重比值,对高血压大鼠病理性左室重构具有保护作用。     

双氢青蒿素对卡氏肺孢子虫肺炎大鼠NO水平的影响

目的　研究双氢青蒿素对卡氏肺孢子虫肺炎大鼠血清和肺泡巨噬细胞上清液 NO水平的影响。　方法　以醋酸可的松皮下注射 Wistar大鼠建立卡氏肺孢子虫肺炎动物模型 ,用 6 0 mg/ kg双氢青蒿素治疗实验大鼠 ,杀鼠取肺 ,用胶原酶消化法分离肺泡巨噬细胞 ,用 L PS刺激培养 72 h,同时设有感染组和正常对照。用 NO试剂盒分别检测大鼠血清和肺泡巨噬细胞上清液 NO活性。　结果　感染组大鼠血清、肺泡巨噬细胞上清液原液以及经 L PS刺激后肺泡巨噬细胞上清液 NO浓度分别为 ( 16 7.3± 2 3.1)、( 141.6± 18.0 )和 ( 12 9.5± 2 8.4) μmol/ L,治疗组分别为 ( 111.8± 40 .6 )、( 136 .3± 35 .1)和 ( 12 9.9± 14.2 ) μmol/ L,正常对照组分别为 ( 87.2± 32 .1)、( 10 9.8± 18.0 )和 ( 136 .2± 30 .5 ) μmol/ L,可见感染组和治疗组大鼠 NO水平均高于相应的正常对照 ,治疗组 NO水平低于相应的感染组。　结论　卡氏肺孢子虫感染可能引起大鼠肺泡巨噬细胞分泌高水平 NO,经双氢青蒿素治疗后 ,PCP大鼠肺泡巨噬细胞分泌 NO水平降低。     

补骨脂与鸦胆子对感染卡氏肺孢子虫大鼠IL-2水平和NK细胞活性的影响

中药补骨脂（10.0 mg/kg）、鸦胆子（1.2 mg/kg）及两药合剂（补骨脂5.0 mg/kg，鸦胆子0.6 mg/kg）治疗PCP卡氏肺孢子虫肺炎（PCP）大鼠。通过检测脾NK细胞活性和血清IL-2水平，探讨两药对PCP大鼠的免疫调节作用。结果表明，与PCP模型对照组比较，补骨脂治疗组血清IL?鄄2诱生水平（526.1±5.5） pg/ml和脾NK细胞活性（27.1%±0.8%）均显著升高（P<0.01），两药合剂组其次［（314.7±6.7) pg/ml， (22.9%±0.9%）（P<0.05）］，鸦胆子组较低［（285.4±6.1） pg/ml， （20.7%±1.0%） （P<0.05）］。补骨脂和鸦胆子具有增强PCP大鼠免疫调节的作用。     

COPD大鼠肺组织IL-17、IL-21、RORγt的表达及辛伐他汀治疗对其的影响

目的 观察辛伐他汀对吸烟所致COPD大鼠肺组织中IL-17、IL-21及转录因子视黄酸相关孤儿受体γt (retinoid-related orphan nuclear receptor gamma t,RORγt)表达的影响,探讨辛伐他汀治疗COPD的价值及其作用机制.方法 SD雄性大鼠随机分为对照组(10只)、吸烟组(11只)及治疗组(10只);观察各组大鼠肺组织的病理改变,采用免疫组织化学方法对大鼠肺组织IL-17、IL-21及RORγt蛋白的分布进行检测;Real time RT-PCR方法对肺组织中IL-17、IL-21及RORγtmRNA的表达进行测定.结果 在支气管黏膜上皮和肺泡间隔内,IL-17、IL-21及RORγt阳性细胞在吸烟组[(90.00±14.02) cells/mm2、(61.18±9.16) cells/mm2、(77.27±7.95) cells/mm2]和治疗组[(72.80±10.79) cells/mm2、(49.40±3.34) cells/mm2、(65.40±5.23) cells/mm2]的表达量均高于对照组[(5.20±4.49) cells/mm2、(8.20±3.16) cells/mm2、(6.80±5.85) cells/mm2] (P＜0.01);且吸烟组的表达量高于治疗组(P＜0.05).肺组织中IL-17、IL-21及RORγt mRNA的表达吸烟组(7.49±2.93、12.22±4.98、4.04±0.21)和治疗组(2.39±0.62、3.78±0.35、1.76±0.25)均高于对照组(1.00±0.00、1.00±0.00、1.00±0.00)(P＜0.01),吸烟组的表达量高于治疗组(P＜0.05).肺泡间隔内的IL-17阳性细胞数与平均内衬间隔呈正相关(r=0.729,P＜0.01),与平均肺泡数呈负相关(r =-0.889,P＜0.01).结论 IL-17、IL-21和RORγt在大鼠COPD形成过程中起着一定的作用,辛伐他汀降低大鼠肺内炎症细胞及炎症因子IL-17、IL-21及RORγt的表达,这种作用是辛伐他汀抑制COPD大鼠肺组织炎症反应和肺病理改变的机制之一.     

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.     

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.     

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.     

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.