前列腺素E_2对人T淋巴祖细胞增殖和T淋巴细胞转化的调节

用半固体的液体培养,观察前列腺素E_2对人外周血T淋巴祖细胞增殖和T淋巴细胞转化的调节。在体外,前列腺素E_2对二者均有明显的抑制作用。加入消炎痛阻滞前列腺素E_2的合成,可使淋巴祖细胞集落增加。     

吡罗昔康凝胶剂和吲哚美辛擦剂治疗骨关节炎的比较

目的：比较吡罗昔康凝胶剂和吲哚美辛擦剂对骨关节炎（ＯＡ）的疗效。方法：６０例ＯＡ病人随机分为２组，吡罗昔康组３０例（男性１４例，女性１６例；年龄５７±ｓ７ａ，病程４±４ｍｏ），每一疼痛区表面涂擦吡罗昔康凝胶１ｇ，ｑｉｄ×２ｗｋ。吲哚美辛组３０例（男性１０例，女性２０例；年龄５６±８ａ，病程２±３ｍｏ），每一疼痛区表面涂擦吲哚美辛擦剂１ｍＬ，ｑｉｄ×２ｗｋ。结果：总有效率吡罗昔康组为９０％，吲哚美辛组为７７％（Ｐ＜０．０５）。结论：吡罗昔康凝胶剂治疗ＯＡ疗效优于吲哚美辛擦剂。     

New Alkyl N,N-Dialkyl-Substituted Amino Acetates as Transdermal Penetration Enhancers

New alcohol derivatives of N,N-disubstituted amino acids with a low toxicity have been synthesized and evaluated for their transdermal penetration enhancing effects on the transport of indomethacin from petrolatum ointments across shed skin of black rat snake (Elaphe obsoleta). The derivatives show excellent penetration enhancement of indomethacin, as high as 3.8 times that of Azone, with decyl N,N-dimethylamino acetate as the lead compound in the series. The release of indomethacin from an ointment containing 1% indomethacin, 5% dodecyl N,N-dimethylamino acetate, and 94% petrolatum was 3.15 µg/min^1/2/cm². Saturation studies performed by incorporating varying concentrations of indomethacin, from 0.1 to 10%, into the ointments and determination of the fluxes of indomethacin demonstrated that the saturated concentration of indomethacin in petrolatum base was approximately 1%. Penetration fluxes of indomethacin (1%) through snake skin increased linearly as the concentration of dodecyl N,N-dimethylamino acetate increased from 2.5 to 15%. Experiments involving the pretreatment of the snake skins with dodecyl N,N-dimethylamino acetate indicated that pre-treatment of the skin increased the skin permeability significantly. Electron micrograph studies on the snake skin treated with dodecyl N,N-dimethylamino acetate show clearly that the enhancer interacted with both the lipid-rich layer (mesos phase) and the keratin-rich layers (both alpha and beta phases).     

钙及cAMP在消炎痛引起的急性胃粘膜损害中的作用

用消炎痛(30mg/kg)致急性胃粘膜损害观察胃粘膜钙及胃组织cAMP含量的变化以及异搏定对消炎痛引起的胃粘膜钙及胃组织cAMP含量变化的影响。结果表明:大鼠给予消炎痛后,随着时间延长,胃粘膜损害密度逐步增加.同时胃粘膜钙含量和胃组织cAMP含量逐步降低。预先给予异搏定(5mg/kg,10mg/kg)可使消失痛引起的急性胃粘膜损害明显减轻,同时,胃粘膜钙及胃组织cAMP含量不再下降,cAMP反而有所升高。     

EFFECT OF ETHAMSYLATE ON CARRAGEENAN-INDUCED RAT PAW OEDEMA: A COMPARISON WITH INDOMETHACIN

1. Ethamsylate (diethylammonium 2,5-dihydroxybenzene sulfonate, Dicynene), a systemic haemostatic agent with an unknown mechanism of action, was tested for anti-inflammatory activity using the carrageenan-induced rat paw oedema test. 2. Ethamsylate was shown to be an effective anti-inflammatory agent with a time course and amplitude of effect similar to that of indomethacin, although the potency was only about 4% of that for indomethacin. 3. When ethamsylate and indomethacin were co-administered they did not show additive effects, suggesting that they do not share a common mode of action. It is proposed that ethamsylate, like indomethacin, may inhibit prostaglandin synthesis. Ulceration produced by indomethacin, it is suggested that it may prove to be a useful addition to, or replacement for, indomethacin in the treatment of inflammatory disorders.     

Non-steroidal anti-inflammatory drugs in the reduction of human alveolar bone loss

Aspirin (ASA) and indomethacin are inhibitors of prostaglandin synthesis and reduce bone resorption in tissue culture stimulated by preparations obtained from human gingival tissue. In a retrospective study, we attempted to determine whether ASA or ASA plus indomethacin exert a bone resorption inhibiting effect on human alveolar bone. Dental radiographs of 75 patients with a history of arthritis and long-term ingestion (greater than 5 years) of ASA were compared with dental radiographs of 75 healthy male volunteers from the VA Dental Longitudinal Study (DLS). Proximal bone loss was measured using a Schei Ruler graded on a 10-point scale. The data indicated that the ASA population presented with significantly fewer sites of 10% or greater mesial and distal bone loss than the healthy control population (P less than 0.05). Mean percentage bone loss for the entire dentition was also lower in the ASA group, although the difference was not statistically significant. As there is no evidence to suggest that inhibition of alveolar bone loss is a natural concomitant of the arthritic process, we conclude that the inhibition of bone loss found in this study was due to the chronic ingestion of ASA or ASA and indomethacin.     

Indomethacin-sensitive monocyte killing defect in a child with disseminated atypical mycobacterial disease

A child with disseminated disease due toMycobacterium avium had progressive disease in spite of 4.5 years of therapy with multiple antimicrobial agents selected on the basis ofin vitro sensitivity testing of her organism. A defect in monocyte bactericidal activity was detected which was correctedin vitro by exposure of the patient's monocytes to indomethacin and normal serum. Indomethacin therapy resulted in normalization of monocyte bactericidal activity and striking, albeit temporary, clinical improvement.     

Effects of Indomethacin on Resting Cerebral Hemodynamic and During Suctioning in Preterm Neonates

The effect of therapeutic doses of indomethacin versus a placebo on cerebral hemodynamics was studied in nine preterm infants using Doppler ultrasound. Three doses of indomethacin (0.2 mg/kg) induced a significant decrease in the mean frequency compared to the placebo. Heart rate, blood pressure, transcutaneous carbon dioxide tension, and transcutaneous oxygen tension remained stable throughout the study. The changes in mean frequency occurred rapidly and were sustained at significantly diminished levels for at least 1 hour. All infants were mechanically ventilated, and the increase of mean frequency secondary to suctioning was significantly attenuated after each dose of indomethacin as compared to the placebo. The results confirmed that infusion of indomethacin caused a reduction in cerebral blood flow, probably by vasoconstriction of cerebral vessels. Indomethacin also seemed to attenuate the cerebrovascular response to hypercapnia induced by endotracheal suctioning. Even so, and because of the alteration of resting cerebral hemodynamics, we do not support the recommendation that indomethacin should be used prophylactically to prevent patent ductus arterious or periventricular intraventricular hemorrhage.     

Early phase microvascular interactions in rat jejunum between nitric oxide and vasopressin following indomethacin administration

Abstract The involvement of endogenous vasopressin in the actions of indomethacin following the concurrent administration of the nitric oxide (NO) synthase inhibitor, N^G-nitro-l -arginine methyl ester (l -NAME), on acute intestinal microvascular permeability has been investigated in the rat. Administration of indomethacin (10mg/kg, s.c.) or L-NAME (10mg/kg, s.c.) alone did not affect jejunal and ileal vascular permeability after 1 h, as determined by the leakage of radiolabelled serum albumin. In contrast, when indomethacin (10mg/kg, s.c.) was injected concurrently with L-NAME (2-10mg/kg, s.c), significant dose-dependent plasma leakage occurred in the jejunum. Pretreatment with l -arginine (300 mg/kg s.c.) 15 min prior to l -NAME prevented these changes in microvascular permeability. Moreover, pretreatment with the vasopressin pressor-receptor antagonist, d(CH₂)₅Tyr(Me)AVP (0.01–0.2m?g/kg, s.c.) dose-dependently attenuated such damage. These findings suggest that following indomethacin administration, the early inhibition of NO synthase leads to acute microvascular injury involving vasopressin in the rat jejunum. This suggests a protective role of NO, formed by constitutive NO synthase, counteracting effectively the deleterious actions of endogenous vasopressin.     

Tiaprofenic acid inhibits mucosal prostaglandin E2 synthesis without delaying experimental gastric ulcer healing

Increasing evidence suggests that non-steroidal anti-inflammatory drugs (NSAID) differ in gastrotoxicity. This study aimed to compare the effects of a short-acting NSAID, tiaprofenic acid, with indomethacin on experimental gastric ulcer healing in a rat model. Similar anti-inflammatory and prostaglandin-inhibitory doses of indomethacin (1mg/kg) and tiaprofenic acid (2mg/kg) were administered to rats with acetic acid-induced ulcers. After 2 weeks treatment, rats were killed and ulcer size determined. In addition, histological sections of ulcers were assessed for ulcer contraction and mucosal regeneration. The degree of inhibition of prostagiandin E₂ (PGE₂) synthesis was 72% at 2h after tiaprofenic acid and 64% at 2h after indomethacin administration, respectively. Rats treated with indomethacin for 2 weeks had significantly larger ulcers, both macroscopically and microscopically, than controls. Rats treated with tiaprofenic acid for 2 weeks had ulcers of a similar size to those of controls. Indomethacin-treated ulcers showed a failure in mucosal regeneration. Tiaprofenic acid-treated ulcers had significantly more regeneration than indomethacin-treated ulcers. We conclude that tiaprofenic acid inhibits mucosal prostaglandin levels but does not inhibit experimental gastric ulcer healing. These findings suggest that inhibition of PGE₂ synthesis is not the only factor in generating gastrotoxicity and that a shift to low gastrotoxic NSAID may be clinically worthwhile.