巴曲抗栓酶对不稳定型心绞痛病人血小板聚集和心肌缺血的影响

目的：观察巴曲抗栓酶对不稳定型心绞痛病人血小板聚集和心肌缺血的影响。方法：不稳定型心绞痛病人２５例，男性１４例，女性１１例，年龄５９±ｓ１０ａ。正常对照组１６例，男性９例，女性７例，年龄４３±１５ａ。治疗组用巴曲抗栓酶首剂１０ＢＵ，ｄ３及ｄ５各用５ＢＵ。用药前后分别作常规心电图及血小板聚集测定。结果：治疗组用药前血小板聚集率高于正常对照组（Ｐ＜０．０１），用药后，治疗组较用药前有显著降低（Ｐ＜０．０１）。心电图ＮＳＴ和∑ＳＴ也于治疗后明显降低（Ｐ＜０．０５）。结论：巴曲抗栓酶对不稳定型心绞痛病人血小板聚集率的降低、心肌缺血的改善有显著作用。     

前列地尔对非胰岛素依赖型糖尿病病人胰岛素及血小板聚集率的影响

目的：探讨前列地尔对非胰岛素依赖型糖尿病（ＮＩＤＤＭ）病人胰岛素及血小板聚集率的影响。方法：应用前列地尔２００μｇ加入０．９％氯化钠注射液５００ｍＬ中静脉滴注，ｑｄ×１０ｄ，治疗５０例ＮＩＤ ＤＭ病人（男性２３例，女性２７例，年龄５８±ｓ１０ａ）。治疗前后测定空腹胰岛素、餐后２ｈ胰岛素及血小板聚集率。结果：前列地尔刺激胰岛素分泌增加和降低血小板聚集率。治疗后的餐后２ｈ胰岛素显著增加（Ｐ＜０．０１），血小板聚集率显著下降（Ｐ＜０．０１，Ｐ＜０．０５）。结论：前列地尔增加ＮＩＤＤＭ病人的胰岛素分泌，降低血小板聚集率     

地奥心血康治疗偏头痛

目的：观察地奥心血康治疗偏头痛是否有效。方法：偏头痛７２例，男性２９例，女性４３例，年龄３７±ｓ７ａ，剂量２００－３００ｍｇ，ｐｏ，ｔｉｄ，治疗时间１－３ｍｏ，结果：治疗前头痛单位指数０．３９±０．２５，治疗后为０．１２±０．１３（Ｐ＜０．０１）。发作频数明显减少。２９例血小板聚集率由治疗前７１％±８％降至治疗后６３％±７％（Ｐ＜０．０１）。该药不良反应轻微。结论：地奥心血康可用以防治偏头痛。     

呋喃丙吡啶对再灌注心肌顿抑兔血小板聚集和血压的影响

目的：探讨心肌顿抑发生后血流动力学和血小板聚集率的变化，以及钙通道拮抗剂呋喃丙吡啶对心肌顿抑兔的保护作用。方法：经冠状动脉结扎法建立兔心肌顿抑模型。用药组缺血前用呋喃丙吡啶静脉给药。结果：对照组再灌注后１５ｍｉｎ血浆最大血小板聚集率达高峰（６１．７６％±９．２２％），用药组同一时间点血浆最大血小板聚集率较对照组低（４０．２３％±５．３９％，Ｐ＜０．０１）。对照组血压较缺血前明显下降（Ｐ＜０．０５），用药组：Ⅰ组（１ｍｇ·ｋｇ－１）血压变化与对照组无统计学差异，Ⅱ组（３ｍｇ·ｋｇ－１）缺血后舒张压下降明显与对照组相比差异显著，随着再灌注时间延长舒张压逐步回升。结论：心肌顿抑发生后伴有血流动力学变化及血小板聚集率增高，缺血前静脉应用呋喃丙吡啶治疗对心肌损伤具有保护作用。     

用流式细胞仪检测血小板P—选择素和血小板—中性粒细胞复合物

用流式细胞仪方法测定血小板的 ＣＤ６２Ｐ和 ＰＮＣ．选 ２５名健康不吸烟自愿者（男 １１名,女 １４名,年龄 ２２－６８岁,平均４２岁）．在用血小板激活物ＡＤＰ前后来评估流式细胞仪检测血小板的方法．ＣＤ６２Ｐ和ＰＮＣ在ＡＤＰ刺激后明显增高［分别为（８．０±２．７）％到（１８．８±６．４）％,Ｐ＜０．０１,（９．４±３．４）％到（１４．５±７．２）％Ｐ＜０．０１）］．论证,流式细胞仪测定血小板的方法是可行的,该方法简便,快速,敏感性高．     

盐酸西替利嗪抗组胺作用的研究

目的：研究盐酸西替利嗪的抗组胺作用。方法：采用离体豚鼠回肠试验、皮肤通透性试验及组胺性休克试验进行观察。结果：盐酸西替利嗪浓度为１０－８～５×１０－７ｍｏｌ·Ｌ－１时，能明显拮抗组胺所致的离体豚鼠回肠收缩反应，使量效曲线平行右移；盐酸西替利嗪给小鼠（０．０５～０．５ｍｇ·ｋｇ－１）、豚鼠（０．０６２５～０．２５ｍｇ·ｋｇ－１）口服给药时，能使组胺所致的皮肤蓝斑面积明显缩小（Ｐ＜０．０１），其作用程度与剂量有关；盐酸西替利嗪０．０６２５～０．５ｍｇ·ｋｇ－１给豚鼠口服时，可显著降低豚鼠组胺性休克的死亡率（Ｐ＜０．０５），延长休克潜伏期（Ｐ＜０．０１），使休克反应程度明显降低（Ｐ＜０．０１）。结论：盐酸西替利嗪具有抗组胺作用。     

依那普利治疗慢性肾小球肾炎

目的：探索依那普利对慢性肾小球肾炎的疗效。方法：４４例慢性肾炎伴肾功能不全、持续性蛋白尿＞２．５ｇ／２４ｈ病人分成２组。治疗组２６例（男性１７例，女性９例；年龄３９±ｓ９ａ）采用依那普利１０～２０ｍｇ／ｄ，维持用药６ｍｏ。对照组１８例（男性１２例，女性６例；年龄３７±８ａ）给予降压药如硝苯地平等．２组病人均给予低蛋白（以优质蛋白为主）、低盐的限制性饮食．结果：依那普利组尿蛋白下降６５％±８％（Ｐ＜０．０１），优于对照组（Ｐ＜０．０１）；血肌酐和肾小球滤过率（ＧＦＲ）无明显变化（Ｐ＞０．０５）．，对照组尿蛋白亦减少（Ｐ＜０．０５），同时伴有血肌酐明显上升（Ｐ＜０．０１）和ＧＦＲ明显下降（Ｐ＜０．０１）。结论：依那普利有保护肾功能作用。     

地奥心血康治疗偏头痛

目的：观察地奥心血康治疗偏头痛是否有效。方法：偏头痛７２例，男性２９例，女性４３例，年龄３７±ｓ７ａ，剂量２００－３００ｍｇ，ｐｏ，ｔｉｄ，治疗时间１－３ｍｏ。结果：治疗前头痛单位指数０．３９±０．２５，治疗后为０．１２±０．１３（Ｐ〈０．０１）。发作频数明显减少。２９例血小板聚集率由治疗前７１％±８％降至治疗后６３％±７％（Ｐ〈０．０１）。该药不良反应轻微。结论：地奥心血康可用以防治偏头痛。     

降纤酶与川芎嗪治疗急性缺血性脑血管疾病的比较

目的：比较降纤酶与川芎嗪治疗急性缺血性脑血管疾病（ＡＩＣＤ）的疗效。方法：降纤酶组３２例（男性１７例，女性１５例；年龄５９±ｓ９ａ）用降纤酶１０ＩＵ加入０．９％氯化钠注射液２５０ｍＬｉｖ，ｄｒｉｐ，ｑｄ×３ｄ，ｄ４剂量减半，ｉｖ，ｄｒｉｐ，ｑｄ×３ｄ，均于１～１．５ｈ滴完。川芎嗪组３１例（男性１７例，女性１４例；年龄５７±８ａ）用川芎嗪２００ｍｇ加入０．９％氯化钠注射液２５０ｍＬ静滴×１２ｄ。结果：降纤酶组与川芎嗪组总有效率分别为９７％与８１％（Ｐ＜０．０１）；血小板聚集率、血液粘度２组均有显著下降，凝血因子Ｉ与血脂仅降纤酶组有显著下降（Ｐ＜０．０５或Ｐ＜０．０１），２组均无严重不良反应。结论：降纤酶治疗ＡＩＣＤ明显优于川芎嗪     

青藤碱单用或加用氯喹和雷公藤多苷治疗类风湿关节炎的比较

目的：观察联合用药治疗类风湿关节炎以提高青藤碱疗效,减少不良反应。方法：联合用药组３５ 例,其中男性１０ 例,女性２５ 例;年龄３９ ａ ±ｓ ８ａ ; 病程５ ａ ±４ ａ 。青藤碱组２８ 例,其中男性８ 例,女性２０ 例;年龄３８ ａ ±９ ａ ;病程５ ａ ±３ ａ 。２ 组均服青藤碱片８０ ｍ ｇ , ｐｏ ,ｔｉｄ ×６ ｍｏ 。联合用药组另加用氯喹０ ．２５ ｇ , ｐｏ ,ｑｎ ×２ ｍ ｏ 后减为０ ．１２５ ｇ , 共服６ ｍｏ ; 雷公藤多苷（ 甙） 片２０ ｍｇ , ｐｏ , ｂｉｄ ×６ｍｏ 。结果：联合用药组和青藤碱组临床缓显率（ 缓解率加显效率） 分别为７４ ％ 和２５ ％ （ Ｐ＜ ０ ．０１） 。不良反应发生率分别为１１ ％ 和３２ ％ （ Ｐ＜ ０ ．０１） 。结论：联合治疗方案治疗类风湿关节炎,比单用青藤碱疗效高,不良反应少。     

Interaction of adriamycin with rat and mouse mast cells: histamine release and cellular uptake

In the present study, we evaluated in mouse and rat mast cells if adriamycin uptake is related to histamine release. In addition, the uptake of the antineoplastic drug and histamine release were studied in other normal and neoplastic cell lines. The effect of sodium cromoglycate was also examined. Adriamycin induced histamine release from mixed or purified mast cells of the mouse and rat. This exocytotic response was quantitatively related to intracellular concentrations of adriamycin. Significant differences in adriamycin uptake were observed between mast cells and other normal and neoplastic cells. When peritoneal mast cells were treated with sodium cromoglycate, histamine release and adriamycin uptake were significantly reduced. In contrast, incubation of other cells with cromoglycate only slightly reduced the cellular concentration of the antineoplastic drug.     

Rat mast cells synthesize a nitric oxide like-factor which modulates the release of histamine.

Rat serosal mast cells were evaluated for their capacity to generate a nitric oxide-like factor by two bioassays: inhibition of platelet aggregation and stimulation of mast cell guanylate cyclase. Incubation of mast cells with human washed platelets, both treated with indomethacin, inhibited thrombin-induced platelet aggregation which was potentiated by superoxide dismutase and reversed by oxyhaemoglobin. When mast cells alone were stirred at 1000 rpm, a time dependent increase in the levels of their cGMP but not cAMP was observed. Preincubation of mast cells with NG-monomethyl-L-arginine significantly enhanced E. coli lipopolysaccharide-evoked histamine release. Our results show that mast cell histamine release can be modulated by an intrinsically generated nitric oxide-like factor.     

Synthetic polycations, polyethylenimines and polyallylamines release histamine from rat mast cells

The effects of synthetic polycations, which induce liposomal membrane fusion without inducing permeability changes, on histamine release from rat mast cells were investigated. Polyethylenimines and polyallylamines with various molecular weights released histamine from mast cells. Acetylated derivatives and triethylentetramine did not release histamine or serotonin from the cells. The histamine release induced by 10 micrograms/ml polyethylenimine with a molecular weight of 600 was inhibited by 1 mM dibutyryl cyclic AMP, but not by 1 MM 8-bromo cyclic GMP; 100 microM D-600, a calcium antagonist; or 30 microM W-7, a calmodulin inhibitor. In the presence of polyethylenimines with molecular weights of 600, 1,200 and 1,800, no detectable release of cytosolic lactate dehydrogenase was observed, indicating that histamine release induced by these polycations was not due to their cytotoxicity. The potencies of these polymers in inducing histamine release depended on their charges, but not on their degrees of polymerization. On the other hand, the actions of polyethylenimine with a molecular weight of 10,000 and polyallylamines with molecular weights of 3,000-4,000 and 10,000 in releasing lactate dehydrogenase were somewhat cytotoxic. These polycations did not induce serotonin release from rat platelets, suggesting that platelets have no coupling system of signal transduction by these polycations. Thus polycations seemed to interact with the mast cell membrane to induce histamine release, and the potencies of these polycations on mast cells seemed to differ from those of their effects on liposomes, which were examined previously.     

Histamine release from mast cells of various species induced by histamine releasing factor from human lymphocytes

The aim of our work was to investigate the effect of histamine releasing factor (HRF), produced in vitro by lymphocytes obtained from atopic and non-atopic asthmatics, on mast cells of various species (mouse - peritoneal mast cells, hamster and rat - peritoneal and pleural mast cells, guinea-pig - mesenteric and pulmonary mast cells). We found that human HRF is able to release histamine from the examined mast cell populations in a dose-dependent fashion. Mast cells from various species differed in their susceptibility to the action of HRF; rat pleural and guinea-pig mesenteric and pulmonary mast cells were the most susceptible, while mouse and hamster peritoneal mast cells - the least susceptible. The presence of 50% D2O in the medium significantly increased HRF-induced histamine release from rat mast cells, while the addition of phosphatidylserine did not change it. HRF-induced histamine release from guinea-pig mesenteric mast cells was not related to sensitization of these cells. We also compared histamine release from guinea-pig pulmonary and mesenteric mast cells induced by human HRF produced in vitro by lymphocytes obtained from atopic and non-atopic asthmatics. We have found that supernatant from atopic asthmatics lymphocyte cultures released significantly more histamine than supernatant from non-atopic asthmatics lymphocyte cultures. Our studies give evidence that human HRF acts across the species barrier and induces histamine release from mast cells of various species. The mechanism of HRF action on mast cells seems to be different from that of allergen.     

The ability of thapsigargin and thapsigargicin to activate cells involved in the inflammatory response.

The ability of thapsigargin and thapsigargicin to activate mast cells and leukocytes has been investigated. The thapsigargin-induced histamine release from rat peritoneal mast cells was found to be dependent on the concentration of thapsigargin, the purity of the mast cell preparations, and the number of mast cells in suspension. Thapsigargin induced histamine release from human basophil leukocytes. Thapsigargin induced beta-glucuronidase and lysozyme release from human neutrophil leukocytes. Thapsigargin caused a release of histamine from mesentery, lung, and heart mast cells of the rat, but only to a minor extent from the corresponding guinea-pig cells. Thapsigargicin induced histamine release from mesentery, lung, and heart mast cells of the rat at concentrations from 0.1 microM but provoked only a release from the corresponding guinea-pig cells in the concentration-range 0.16 to 1.6 microM. Thapsigargin increased the cytoplasmic free calcium level in intact human blood platelets at concentrations from 3.0 nM.     

The effect of platelet-activating factor on histamine release from rat peritoneal mast cells.

The effect of platelet-activating factor (PAF) on histamine release from peritoneal mast cells of adult and young male rats was investigated. PAF alone tended to release histamine from the mast cells of adult and young rats, although very slightly. On the other hand, PAF significantly inhibited the histamine release induced by the Ca2+ ionophore A23187 in mast cells obtained from rats of either age group, but not that by compound 48/80. Such inhibition was not seen with lyso-PAF. CV-3988, a PAF antagonist, antagonized the inhibitory effect of PAF on the A23187-induced histamine release in mast cells from adult and young rats. These results suggest that PAF does not have a strong histamine-liberating action on mast cells, and that PAF inhibits the calcium influx into mast cells through the activation of PAF receptors.     

A place for free radicals in platelet-derived histamine releasing factor (PDHRF) and evidence that histaminergic receptors modulate platelet aggregation.

The release of histamine from rat serosal mast cells induced by coincubation with resting and activated human platelets, or by exposure of mast cells to supernatants obtained from activated platelets, is significantly reduced by anti-free radical interventions, and is coupled with the generation of membrane lipid peroxidation products. These results suggest free radical participation in the activity of PDHRF. Human platelets possess specific binding sites for an H1-receptor antagonist, suggesting that H1-receptors could modulate the intracellular calcium levels in a pro-aggregatory fashion.     

Induction of histamine release from human skin mast cells by bradykinin analogs

Kinins are potent proinflammatory peptides that induce histamine release from rodent mast cells. We examined the ability of bradykinin, lysylbradykinin and a series of kinin analogs to cause histamine release from human basophils, human lung mast cells and human skin mast cells. At concentrations ranging from 0.1 microM to 1 mM, bradykinin failed to cause histamine release from any of the human histamine-containing cells studied. Lysylbradykinin was also without effect on basophils and lung mast cells, but was a weak secretagogue for human skin mast cells, inducing 5.5 +/- 3% (mean +/- SD) of total cellular histamine release at a concentration of 10(-5) M. Similarly, when sixteen recently developed bradykinin antagonists were examined, these compounds had no effect on basophils or lung mast cells but all sixteen induced dose-dependent histamine release from skin mast cells. The release process was temperature dependent and, at a concentration of 10(-5) M, the antagonists induced 8-27% histamine release. Although preincubation of cells with 10(-3) M bradykinin or des(Arg9) bradykinin significantly inhibited antagonist-induced histamine release, the requirement for such high concentrations of these peptides to cause inhibition suggested that histamine release is not mediated by either B1 or B2 kinin receptors. To understand further the mechanism of histamine release, we examined a series of bradykinin analogs with single amino acid substitutions in the bradykinin sequence. Replacement of proline7 in the bradykinin sequence with D-phenylalanine is the essential change used to convert kinin analogs into antagonists, and 10(-5) M [DPhe7]-bradykinin induced 8-10% histamine release. Other analogs, devoid of antagonist activity, however, such as [DPhe6]-bradykinin and [LPhe7]-bradykinin were able to induce equivalent levels of histamine release. The ability to induce histamine release appears to be related, at least in part, to aromaticity, since [DTrp6]-bradykinin and [DTrp7]-bradykinin induced greater amounts of histamine release than equivalent [DPhe]-analogs, causing approximately 20% histamine release at 10(-5) M. By contrast, [DAla7]-bradykinin was an ineffective stimulus. In summary, a single amino acid substitution can convert bradykinin into a secretagogue for human skin mast cells. The ability of kinin analogs to induce histamine release from skin mast cells, but not lung mast cells or basophils, emphasizes the heterogeneity of human histamine-containing cells.     

Desensitization of rat mast cells: studies of some effects of anti-allergic drugs

Peritoneal mast cells from rats immunized with dinitrophenylated ovalbumin (DNP-OA) or normal cells passively sensitized with mouse anti-DNP-OA were incubated in vitro with DNP-bovine serum albumin in the absence of Ca++. This procedure induced desensitization of the cells, such that histamine release was inhibited on subsequent challenge with OA, in the presence of Ca++. The phenomenon of desensitization is supposed to involve early stages in the histamine release process and, thus, two anti-allergic drugs, disodium cromoglycate and doxantrazole, which inhibit an early event(s), were added with the Ca++ -free antigen to investigate whether they had any effect on desensitization. The inhibition of final histamine release caused by each drug and that due to desensitization were approximately additive. It was concluded that the drugs did not influence desensitization of rat mast cells. Thus, their activity was consistent with an effect on an event in the histamine release process, occurring after the generation of the activated stage believed to be responsible for desensitization.     

Immunopharmacological actions of the new antiallergic drug butyl 3'-(1H-tetrazol-5-yl)oxanilate. 2nd communication: inhibitory effects on histamine release from rat mast cells and lung fragments

The effects of butyl 3'-(1H-tetrazol-5-yl)oxanilate (WP-833), a new antiallergic drug, on its ability to inhibit histamine release from both peritoneal mast cells and lung fragments of rats were investigated. WP-833 inhibited in a dose-dependent fashion immunoglobulin E (IgE)-mediated histamine release from mast cells. Such potent inhibition was observed in glucose-free as well as complete Tyrode's solution but neither in Ca2+-free nor D2O-supplemented Tyrode's solution. In addition, WP-833 significantly increased intracellular cyclic adenosine monophosphate (AMP) levels in purified mast cells. On the other hand, WP-833 inhibited compound 48/80-but not calcium ionophore A23187-induced histamine release from normal mast cells. Also both IgE- and IgG-mediated histamine release from lung fragments were inhibited by WP-833. WP-833 showed non-competitive inhibition of cyclic AMP-dependent phosphodiesterase derived from lung preparations.