绒猴口服200mg碘油有效供碘时间及药代动力学研究

为了探讨目前国内广泛使用的２００ｍｇ小剂量碘油口服后的药代动力学和代谢规律，我们选择了灵长目动物绒猴为实验对象，以药代动力学方法，对尿碘、粪碘、血碘、ＴＳＨ、Ｔ３、Ｔ４等观测指标，进行了严格的观察。结果证明：绒猴在口服该剂量碘油后，吸收迅速，生物利用率高，其主要排泄途径是尿液。其排泄方式为二房室模型（具有快相和慢相）；碘在体内的贮存时间为１８０～２７０天（６～９个月）。     

胺碘酮与其代谢物去乙基胺碘酮的比较研究

目的　研究健康受试者单剂和连续口服胺碘酮后原形药物和活性代谢物去乙基胺碘酮的药代动力学特点及相互关系。方法　 36例健康男性受试者分两组。单剂量组 2 0例 ,服药 80 0mg/次 ;多剂量组 1 6例 ,服药 60 0～ 80 0mg/d ,连续服药至停药标准。采用反相HPLC方法同时测定受试者胺碘酮和去乙基胺碘酮血药浓度 ,并计算药代动力学参数。主要药代动力学参数比较采用方差分析。结果　 (1 )单剂量组 :胺碘酮和去乙基胺碘酮的达峰时间 (Tmax)分别为 (5 2± 1 5)h和 (8 6± 3 2 )h ,峰浓度 (Cmax)分别为 (0 764± 0 383)mg/L和 (0 1 2 6± 0 0 71 )mg/L ,0至 48h取样的血药浓度 时间曲线下面积 (AUC0 4 8)分别为 (1 0 593± 4 977)mg·h·L- 1 和 (3 936± 1 2 88)mg·h·L- 1 ;(2 )多剂量组 :胺碘酮和去乙基胺碘酮间Tmax和末端消除速率常数 (Ke)差异无显著性 (P >0 0 5) ;其余药代动力学参数Cmax、Tmax、AUC0 4 8等两者之间差异有显著性 (P <0 0 1 )。口服两种负荷剂量后 ,代谢物的各药代动力学参数两组间差异无显著性。结论　无论是单剂或短期连续口服胺碘酮 ,其原形药物、去乙基胺碘酮均存在滞后作用 ,临床给药时应考虑原形药物及其代谢物累积药效的影响     

2种剂量碘油丸口服后1年内儿童尿碘排泄观察

目的：了解2种剂量碘油丸口服后儿童尿碘排泄值和排泄规律。方法：选取7－12岁学生，分3个组，分别给予0．2，0．3g和安慰剂量碘油丸口服，观察尿碘排泄情况，结果：服碘油丸后5h尿碘达高峰，尿碘中位数分别为250000和232500ug/L,7d内排泄最快，14天以后排泄缓慢，3个月后尿碘中位数在200ug/L，上下波动，11个月后与对照组相同，第1，3，7天服0．3克组的尿碘中位数均大于服0．2克组，差异有显著,意义，第14天以后直到观察结束，2个组的尿碘中位数差异无显著意义。结论：2种剂量碘油丸口服后尿碘排泄规律一致，均有一个急剧排泄的阶段，时间很短，尿碘值很高，0．3g组高于0．2g组，表明多服多排，当用碘油丸作为补碘措施时，以小剂量为宜。／     

HPLC法测定健康人血浆中甲巯咪唑浓度及药物动力学研究

12名男性健康志愿者一次口服 2 0mg甲巯咪唑片后 ,以HPLC法测定血浆甲巯咪唑浓度 ,用非房室模型参数估算法计算药物动力学参数。主要的药物动力学参数为峰时间 (Tmax) ( 1.5 2± 0 .96)h ,峰浓度 (Cmax) ( 3 91± 77) μg/L ,曲线下面积 (AUC) 0～ 2 4h( 3 3 84± 93 1) μg·L-1·h ,AUC0～∞( 3 845± 93 0 ) μg·L-1·h ,平均驻留时间 (MRT) ( 9.2 5± 1.3 5 )h ,消除半衰期 (T1/ 2 ) ( 8.68± 2 .85 )h。药物动力学特征表明该制剂口服后吸收较快 ,体内消除较慢 ,药物动力学参数个体间存在较大差异。     

分次口服碘油后碘的排泄率和供碘有效期的实验研究

目的：探讨绒猴分７次口服２００ｍｇ碘油后碘的排泄率及供碘有效期。方法；以药代动力学的方法研究碘的排泄过程。结果：分次口服碘油碘的半衰期和有效期较１次性口服等剂量碘油的半衰期和有效期延长。低碘绒猴的半衰期和有效期较正常绒猴有轻度缩短。     

哺乳妇女口服200mg碘油胶丸后乳汁碘及婴幼儿尿碘排泄研究

目的了解200 mg碘油胶丸对哺乳妇女乳汁碘及婴幼儿尿碘的有效保护期,并探索碘排泄规律。方法在阿克苏地区库车县牙哈镇四村选择了109名近半年内未服用过碘油丸的19～36岁哺乳期妇女及20天～18个月婴幼儿,用现场干预的方法,并于服药后的第1、3、7、14、30、50、75、100 d分别采集实验组及对照组的妇女乳汁及婴幼儿尿样,进行碘含量测定。结果本次研究哺乳妇女口服200 mg碘油胶丸后,乳汁碘及婴幼儿尿碘中位数在干预后第一天达到峰值,其值为1004.1μg/L、1383.9μg/L,1～7 d维持高值段,7～14 d碘值下降较快,14 d以后碘值缓慢下降,75～100 d碘值缓慢上升。干预组与对照组经非参数wilcoxon秩和检验显示,除了乳汁碘100 d外,干预组均大于对照组,差异有统计学意义(P<0.05)。结论库车牙哈镇哺乳期妇女通过口服200 mg碘油胶丸可对婴幼儿尿碘最长保护期为100 d。     

药物代谢动力学原理在心血管药物方面的应用

药物代谢动力学(简称药代动力学)是研究药物在体内吸收、分布、代谢和排泄的量变规律.合理地应用药代动力学原理以及所用药物的动力学特征,有助于拟订给药方案,使药物血清浓度维持在最佳"治疗范围"内.药物吸收、分布、代谢和排泄的速率通常与药物浓度成比例,遵照一级或线性动力学规律.例如,当口服某种药物时,最初胃肠道内的药物浓度较高,则其吸收速率亦较快.当药物开始被吸收后,胃肠道内浓度减低,药     

双环醇对大鼠口服他克莫司和阿托伐他汀后血浆药代动力学的影响

目的研究双环醇对大鼠口服他克莫司和阿托伐他汀后血浆药代动力学的影响,为双环醇与其他临床药物合理应用提供实验依据。方法 SD大鼠分为空白对照组和双环醇组,分别口服给予0.5%羧甲基纤维素(CMC)和双环醇200 mg·kg~(-1)·d~(-1),连续给药7 d。实验第8天两组动物分别口服给予他克莫司(2 mg/kg)和阿托伐他汀(10 mg/kg)。应用LC/MS/MS分析方法测定各组动物给药后不同时间点的血药浓度。采用WinNonLin软件进行非房室模型分析,计算血浆药代动力学参数。结果空白对照组和双环醇给药组大鼠(200 mg·kg~(-1)·d~(-1),7 d)口服他克莫司及阿托伐他汀后的血浆血药峰浓度(Cmax)及药时曲线下面积(AUC)差异无统计学意义(P0.05)。结论双环醇多次给药后对合用药物他克莫司和阿托伐他汀在大鼠体内血浆药代动力学无明显影响。     

高脂餐与空腹顿服胺碘酮的药代动力学对比研究

目的　比较空腹和高脂餐后顿服胺碘酮的药代动力学变化 ,探讨饮食对胺碘酮药代动力学的影响。方法　 8名健康男性志愿者 ,年龄 (2 1 6± 1 2 )岁 ,体重 (6 5 8± 5 6 )kg。志愿者分别在空腹12h和进食标准脂肪早餐 (含黄油 1 5 g/kg体重 )后顿服胺碘酮 80 0mg ,两次服药间隔 12周。高效液相色谱法测定胺碘酮及其代谢产物去乙基胺碘酮浓度 ,计算餐后与空腹服药后药代动力学参数及相对生物利用度。结果　结果显示高脂餐后胺碘酮的血浆浓度较空腹服药明显增高。餐后胺碘酮的峰浓度(Cmax)和血药浓度 时间曲线下面积 (AUC0 t)均较空腹服药显著升高 [Cmax(2 330± 12 14)ng/ml对 (90 3± 35 3)ng/ml;AUC0 t(2 72 6 6± 86 6 7)ng·h·ml-1对 (12 82 5± 5 985 )ng·h·ml-1](P <0 0 1) ;消除半衰期 (t1/ 2 )明显延长 [(2 9 6± 9 8)h对 (17 0± 5 3)h](P <0 0 1) ;达到峰值时间 (Tmax)基本不变 [(4 6±1 2 )h对 (4 6± 1 5 )h]。根据各受试者的AUC计算出高脂餐后服药的相对生物利用度为 2 39%±75 %。结论　高脂餐后服药增加胺碘酮的吸收 ,显著增加胺碘酮的血药浓度 ,同时减慢胺碘酮自体内的消除 ,提示进食高脂餐可能影响药物的疗效。     

口服碘化豆油在人和动物体内吸收、分布、排泄的研究

1983年11月至1984年11月对病区方城县券桥乡大刘庄16名18～30岁的健康人随机分两组,每组8人,男女各半。口服碘油组每人一次服1ml,肌肉注射组肌注1ml。投药前均测定PBI、尿碘,口服组测了粪碘,投药后观察尿碘排泄情况。口服后第7天PBI达最高值,第15天PBI稳定,服药后一年PBI为服药前的1.28倍,半衰期为3个月,推算储存时间为1.76年。口     

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.     

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.     

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.     

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.