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Repetitive prenatal glucocorticoids increase lung endothelial nitric oxide synthase expression in ovine fetuses delivered at term

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PEDIATRIC RESEARCH 2000年第1期48卷 75-83页

作者： Grover, TR Ackerman, KG Le Cras, TD Jobe, AH Abman, SH Univ Colorado Sch Med Pediat Heart Lung Ctr Denver CO 80262 USA Univ Colorado Sch Med Dept Pediat Denver CO 80262 USA Childrens Hosp Med Ctr Cincinnati OH 45229 USA

Antenatal administration of glucocorticoids has been shown to improve postnatal lung function after preterm birth in the ovine fetus. Mechanisms of steroid-induced lung maturation include increased surfactant production and altered parenchymal lung structure. Whether steroid treatment also affects lung vascular function is unclear. Because nitric oxide contributes to the fall in pulmonary vascular resistance at birth, we hypothesized that the improvement of postnatal lung function of preterm lambs after treatment with prenatal glucocorticoids may be in part caused by an increase in endothelial nitric oxide synthase (eNOS) activity. To determine whether glucocorticoid treatment increases lung eNOS expression, we measured eNOS protein content by Western blot analysis of distal lung homogenates and immunostaining of formalin-fixed lungs from ovine fetuses delivered at preterm and term gestation after prenatal administration of glucocorticoids. Treatment protocols were followed in which ewes were treated with intramuscular betamethasone (0.5 mg/kg) at single or multiple doses at weekly intervals, and fetuses were delivered at 125, 135, or 145 d gestation. All groups were compared with saline-treated controls. Western blot analysis of whole lung homogenates demonstrated a 4-fold increase in eNOS protein content in lambs treated with repetitive doses of glucocorticoids and delivery at term (145 d;p < 0.002). In addition, a small increase in lung eNOS protein content was seen in lambs treated with a single dose of betamethasone at 128 d gestation with delivery at 135 d gestation. In comparison with control animals, there were no differences in lung eNOS content from the remaining lambs treated with glucocorticoids when delivery occurred at preterm ages (125 and 135 d). Immunostaining showed eNOS predominantly in the vascular endothelium in all vessel sizes. Pattern of staining was not altered by treatment with antenatal glucocorticoids. We conclude that maternal treatment

关键词：动物新生倍他米松/投药和剂量倍他米松/药理学剖宫产术用药计划表孕龄糖皮质激素类/药理学免疫组织化学注射肌肉内肺/药物作用肺/胚胎学肺/酶学一氧化氮合酶/代谢一氧化氮合酶Ⅲ型参考值绵羊动物女(雌)性妊娠

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Topical therapy for psoriasis with the use of augmented betamethasone and calcipotriene on alternate weeks

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JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY 2000年第1期43卷 61-65页

作者： Singh, S Reddy, DCS Pandey, SS Banaras Hindu Univ Dept Dermatol Inst Med Sci Varanasi 221005 Uttar Pradesh India Banaras Hindu Univ Dept Prevent Med Inst Med Sci Varanasi 221005 Uttar Pradesh India

Background: Topical corticosteroids, commonly used for psoriasis, show diminished response on continuous use. Objective: We tested efficacy of topical corticosteroid and calcipotriene used on alternate weeks versus daily corticosteroid in patients with psoriasis. Methods: In a randomized, observer-blind design, the experimental group of 25 patients with stable plaque psoriasis received augmented betamethasone dipropionate 0.05% cream once daily in the first and third weeks and calcipotriene 0.005% ointment twice daily in the second and fourth weeks. The control group of 27 patients received augmented betamethasone once daily for 4 weeks. Results: The experimental regimen was more effective than the control regimen as evidenced by (1) more patients with at least a 90% reduction in Psoriasis Area and Severity Index (PASI) score (difference 49.5%, 95% confidence interval [CI], 26.1%-72.9%, P<.001), (2) lower PASI after 2 weeks (P less than or equal to.04), and (3) greater percentage reduction in PASI after 2 and 4 weeks (difference 23.1% [CI, 11.1%-35.1%] and 46.4% [28.9%-63.8%], respectively;P<.001). The study had power of 93.7%. No patient had skin irritation. Conclusion: Use of augmented betamethasone and calcipotriene on alternate weeks is more effective than daily corticosteroid and represents a novel strategy for treating psoriasis.

关键词：投药局部消炎药/投药和剂量倍他米松/投药和剂量倍他米松/类似物和衍生物骨化三醇/投药和剂量骨化三醇/类似物和衍生物皮肤科用药/投药和剂量糖皮质激素类银屑病/药物疗法单盲法治疗结果成年人女(雌)性人类男(雄)性中年人

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Altered immune function in human newborns after prenatal administration of betamethasone: Enhanced natural killer cell activity and decreased T cell proliferation in cord blood

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PEDIATRIC RESEARCH 1999年第3期45卷 306-312页

作者： Kavelaars, A van der Pompe, G Bakker, JM van Hasselt, PM Cats, B Visser, GHA Heijnen, CJ Univ Utrecht Het Wilhelmina Kinderziekenhuis Dept Immunol NL-3508 AB Utrecht Netherlands Univ Utrecht Het Wilhelmina Kinderziekenhuis Dept Neonatol NL-3508 AB Utrecht Netherlands Univ Utrecht Het Wilhelmina Kinderziekenhuis Dept Obstet & Gynecol NL-3508 AB Utrecht Netherlands

During the course of human pregnancy, glucocorticoid (GC) treatment is given when preterm delivery is expected. This treatment is successful in stimulating the development of the fetal lung. However, in animal studies, a number of side effects of perinatal GC treatment have been described. The aim of the present study was to evaluate in humans the effects of antenatal GC treatment on development of the immune system. In addition, we examined the development of immune reactivity in infants born preterm and at term who did not receive GC treatment antenatally. We tested mitogen-induced T cell proliferation, natural killer cell activity, and lipopolysaccharide-induced IL-6 production in cord blood samples. We found that there is a significant effect of gestational age on the capacity of T cells to proliferate and of natural killer cells to kill K562 tumor cells. The capacity to produce IL-6 does not change between gestational age 26 and 41 wk. Moreover, our results show that antenatal treatment with GC does have immunomodulatory effects: T cell proliferation is decreased in infants born very preterm (gestational age 26-31 wk) as well as in infants born between 32 and 36 wk of gestation. In contrast, the activity of natural killer cells is only increased in CC-treated infants born between 26 and 31 wk. We did not observe a significant effect of antenatal GC treatment on the capacity to produce IL-6.

关键词：倍他米松/投药和剂量细胞分裂胚胎和胎儿发育/药物作用胚胎和胎儿发育/免疫学胎血/免疫学糖皮质激素类/投药和剂量免疫系统/药物作用免疫系统/胚胎学注射肌肉内杀伤细胞天然/免疫学淋巴细胞活化/药物作用产前暴露迟发效应 T淋巴细胞/免疫学女(雌)性人类婴儿新生妊娠

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Histologic chorioamnionitis, antenatal steroids, and perinatal outcomes

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OBSTETRICS AND GYNECOLOGY 2000年第3期96卷 333-336页

作者： Elimian, A Verma, U Beneck, D Cipriano, R Visintainer, P Tejani, N New York Med Coll Dept Obstet & Gynecol Valhalla NY 10595 USA New York Med Coll Dept Pathol Valhalla NY 10595 USA New York Med Coll Grad Sch Hlth Sci Valhalla NY 10595 USA

Objective: To determine the perinatal effects of histologic chorioamnionitis on preterm neonates and the effectiveness of antenatal steroids in the presence of histologic chorioamnionitis. Methods: We studied neonates at our institution who weighed 1750 g or less at birth from January 1990 through December 1997. The population was stratified primarily by presence of histologic chorioamnionitis and secondarily by exposure to antenatal steroids. Subgroups were compared by various perinatal outcomes and confounding variables. Student t test, chi(2), Fisher exact test, and logistic regression were used for analysis. Results: Among 1260 neonates entered, the placentas of 527 had evidence of histologic chorioamnionitis and 733 did not. Those with histologic chorioamnionitis had a lower mean gestational age, lower birth weight, and higher rate of major neonatal morbidities than those without it. After adjusting for confounding variables, histologic chorioamnionitis independently associated with lower gestational age, lower birth weight, and neonatal death. Among neonates exposed to antenatal steroids who had histologic chorioamnionitis, there was a significantly lower incidence of low Apgar scores (18% compared with 33.5%, P <.001), respiratory distress syndrome (RDS) (39.6% compared with 55.9%, P <.001), intraventricular hemorrhage and periventricular leukomalacia (21.9% compared with 36.9%, P <.001), major brain lesions (7.7% compared with 18.4%, P < .001), patent ductus arteriosus (14.8% compared with 23.7%, P = .018), and neonatal death (8.3% compared with 16.2%, P = .02), with no increase in rate of proven neonatal sepsis (18.3% compared with 14%, P = .24). Conclusion: Histologic chorioamnionitis increases major perinatal morbidity through its association with preterm birth and is independently associated with neonatal death. In the presence of histologic chorioamnionitis, antenatal steroids significantly decreased the incidence of RDS, intraventricular hemorrhage and

关键词：消炎药/投药和剂量消炎药/副作用倍他米松/投药和剂量倍他米松/副作用绒毛膜羊膜炎/药物疗法绒毛膜羊膜炎/病理学用药计划表胚外膜/病理学死胎/病理学婴儿早产疾病/病理学婴儿早产疾病/预防和控制注射肌肉内胎盘/病理学妊娠结局治疗结果女(雌)性人类婴儿新生妊娠

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COMPARATIVE DOUBLE-BLIND TRIAL OF INTRA-ARTICULAR INJECTIONS OF 2 LONG-ACTING FORMS OF BETAMETHASONE

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SCANDINAVIAN JOURNAL OF RHEUMATOLOGY 1975年第3期4卷 118-120页

作者： HUSBY, G KASS, E SPONGSVEEN, KL OSLO SANITETSFORENINGS RHEUMATISM HOSP AKERSBAKKEN 27OSLO 1NORWAY

Two injectable betamethasone preparations, betamethasone dipropionate/betamethasone phosphate and betamethasone acetate/betamethasone phosphate were compared in a controlled trial on 22 "matched patient pairs" with rheumatic diseases. The two preparations were injected intra-articularly in knee joints affected by active synovitis. The time until onset of action and the duration of clinically adequate anti-inflammatory effect were recorded. All injections produced clinically significant effects. The interval before recurrence of symptoms varied from 2 days to more than 3 months. The dipropionate form showed statistically significantly longer duration of action. No difference was noted in the time until onset of action. Local side effects were not observed. The double-blind method of clinical evaluation proved useful in comparing duration of action between long-acting corticosteroids.

关键词：关节炎反应性/药物疗法关节炎类风湿/药物疗法倍他米松/投药和剂量倍他米松/类似物和衍生物倍他米松/治疗应用临床试验(主题) 迟效制剂药物评价注射关节内脊柱炎强直性/药物疗法成年人女(雌)性人类男(雄)性中年人

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Antenatal glucocorticoids alter postnatal preterm lamb renal and cardiovascular responses to intravascular volume expansion

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PEDIATRIC RESEARCH 2000年第5期47卷 622-627页

作者： Smith, LM Ervin, MG Wada, N Ikegami, M Polk, DH Jobe, AH Univ Calif Los Angeles Harbor UCLA Med Ctr Sch Med Martin Res CtrDept PediatPerinatal Res Labs Torrance CA 90502 USA Univ Calif Los Angeles Harbor UCLA Med Ctr Sch Med Dept Obstet & Gynecol Torrance CA 90502 USA

We assessed renal and cardiovascular function in preterm newborn lambs after antenatal glucocorticoid exposure. Pregnant ewes were randomly assigned to receive betamethasone or saline via either direct fetal or maternal injection at 122 d gestation. Lambs were delivered 15 h later, and cardiovascular and renal function was assessed. Two hours after delivery, baseline urine flow, urinary sodium excretion, and urinary osmolar clearance were similar in all groups. Volume expansion (saline, 2.58 of body weight, for 10 min) increased values for urine flow (0.23 +/- 0.04 to 0.58 +/- 0.09 ***(-1).kg(-1)), urinary sodium excretion (29.7 +/- 5.8 to 76.2 +/- 12.3 mu ***(-1).kg(-1)), and osmolar clearance (12.2. +/- 1.2 to 24.3 +/- 1.6 mL/100 mL GFR) in the fetal group. Increases in urine values were also observed in the maternal group, but control values did not change significantly. Mean arterial pressure was increased in both betamethasone-treated groups relative to controls. Short-term antenatal betamethasone exposure I) augments preterm newborn kidney adaptive responses to acute volume expansion, and 2) increases postnatal blood pressure in preterm newborn lambs.

关键词：醛固酮/血液血管紧张素Ⅱ/血液倍他米松/投药和剂量血量/生理学心血管系统/胚胎学乙醇胺类/血液胎血/化学肾小球滤过率/药物作用糖皮质激素类/投药和剂量血流动力学/药物作用输注静脉内注射肌肉内肾/药物作用肾/胚胎学肾/生理学分娩过早/药物疗法产前暴露迟发效应肾循环/药物作用肾素/血液绵羊氯化钠/投药和剂量尿动力学/药物作用水电解质平衡/药物作用动物女(雌)性妊娠

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Adrenal suppression induced by betamethasone in women at risk for premature delivery

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OBSTETRICS AND GYNECOLOGY 2000年第2期96卷 287-290页

作者： Helal, KJ Gordon, MC Lightner, CR Barth, WH Wilford Hall USAF Med Ctr Dept Obstet & Gynecol Lackland AFB TX 78236 USA Ehrling Bergquist Hosp Bellevue WA USA

Objective: To determine whether betamethasone administered to women at risk of preterm delivery causes adrenal suppression. Methods: Ten women at risk of preterm delivery had three weekly low-dose (1 mu g) ACTH stimulation tests with the first one between 24 and 25 weeks' gestation. Immediately after the first and second ACTH stimulation tests, we gave each woman a 12-mg betamethasone dose intramuscularly and repeated it 24 hours later. The third ACTH stimulation test was 1 week after the second course of betamethasone. Serum cortisol levels were measured before (baseline) and 30 minutes after ACTH administration. Results: All subjects had normal baseline and stimulated cortisol levels for the first ACTH stimulation test. Mean baseline serum cortisol levels decreased with each ACTH stimulation test, from 25.4 +/- 4.8 mu g/dL (before betamethasone) to 4.3 +/- 4.0 mu g/dL (1 week after the second course of betamethasone) (P < .001). The mean stimulated cortisol levels also decreased from 33.0 +/- 4.3 mu g/dL (before betamethasone) to 11.8 +/- 6.4 mu g/dL (1 week after the second course of betamethasone) (P < .001). Compared with initial ACTH stimulation tests, laboratory evidence of adrenal suppression occurred in four patients 1 week after the first course of betamethasone and in seven patients after the second course. No signs or symptoms of Addisonian crisis occurred antepartum or intrapartum. Conclusion: Antenatal administration of betamethasone produced measurable adrenal suppression in women at risk of preterm delivery. The number of women with adrenal suppression increased each week that antenatal betamethasone was repeated.

关键词：肾上腺皮质/药物作用肾上腺皮质功能试验消炎药/投药和剂量消炎药/药理学倍他米松/投药和剂量倍他米松/药理学队列研究氢化可的松/血液注射肌肉内分娩过早/代谢前瞻性研究成年人女(雌)性人类妊娠

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臭氧联合复方倍他米松和透明质酸钠治疗膝关节骨性关节炎的临床疗效

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医学临床研究 2012年第8期29卷 1584-1585页

作者：毛鑫城郑铭陟王沪湘(编辑) 湖南省株洲市一医院麻醉科湖南株洲412000

【目的】观察臭氧联合得宝松和透明质酸钠（HA）治疗膝关节骨性关节炎（KOA）的近期临床疗效。【方法】将180例KOA患者随机分为两组，每组90例。臭氧组采用臭氧联合得宝松和HA关节内注射，对照组采用单纯HA关节内注射，比较两组疗效、... 详细信息

【目的】观察臭氧联合得宝松和透明质酸钠（HA）治疗膝关节骨性关节炎（KOA）的近期临床疗效。【方法】将180例KOA患者随机分为两组，每组90例。臭氧组采用臭氧联合得宝松和HA关节内注射，对照组采用单纯HA关节内注射，比较两组疗效、疼痛和关节活动度及Lysholm膝关节评分变化。【结果】臭氧组总有效率为87．78％（79／90），高于对照组（71．11％），且两组相比较差异有显著性（P〈O．05），两组疼痛减轻，膝关节活动度和Lysholm评分较治疗前均提高，但臭氧组在疼痛扣Lysholm评分方面改善更显著（P〈O．05）。【结论】臭氧联合得宝松和HA是治疗KOA较好的方法。

关键词：骨关节炎,膝/治疗臭氧倍他米松/投药和剂量透明质酸/投药和剂量

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Effect of anti-inflammatory agents on corneal wound-healing process after surface excimer laser keratectomy

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JOURNAL OF CATARACT AND REFRACTIVE SURGERY 2000年第3期26卷 426-431页

作者： Kaji, Y Amano, S Oshika, T Obata, H Ohashi, T Sakai, H Shirasawa, E Tsuru, T Yamashita, H Univ Tokyo Fac Med Dept Ophthalmol Bunkyo Ku Tokyo 1138655 Japan New York State Univ Dept Cell Biol New York NY USA Santen Pharmaceut Co Ltd Nara Res & Dev Ctr Nara Japan Jichi Med Sch Dept Ophthalmol Minami Kawachi Tochigi Japan Yamagata Univ Sch Med Dept Ophthalmol Yamagata 99023 Japan

Purpose: To investigate the effect of anti-inflammatory agents on conjunctival inflammation and corneal haze formation after excimer laser keratectomy. Setting: Department of Ophthalmology, University of Tokyo Faculty of Medicine, Tokyo, Japan. Methods: After excimer laser keratectomy was performed in 21 rabbits (42 eyes), saline, betamethasone 0.1%, or diclofenac 0.1% was topically applied 6 times a day for weeks and then 3 times a day for 8 weeks. The degree of conjunctival inflammation was determined 1, 2, 3, and 7 days after the keratectomy. The degree of corneal haze was quantitatively measured using a digital analyzer before and once a week after the keratectomy. The expression of type IV collagen in the corneas at baseline and 4 and 2 weeks after the keratectomy was examined immunohistochemically. Results: Compared with saline, betamethasone and diclofenac significantly decreased early-phase conjunctival inflammation. Betamethasone significantly inhibited corneal haze formation compared with saline at 3 to 5 and 8 to 12 weeks. Diclofenac did not inhibit corneal haze formation significantly. Although betamethasone tended to be more effective in inhibiting corneal haze formation and deposition of type IV collagen than diclofenac, there was no statistical difference between the 2 anti-inflammatory agents. Conclusion: Topically applied betamethasone effectively suppressed corneal haze formation after excimer laser keratectomy. Diclofenac was not statistically effective in inhibiting corneal haze formation. J Cataract Refract Surg 2000;26:426-431 (C) 2000 ASCRS and ESCRS.

关键词：消炎药/投药和剂量消炎药非甾类/投药和剂量倍他米松/投药和剂量胶原/代谢结膜炎/预防和控制角膜/药物作用角膜/代谢角膜/病理学角膜/外科学角膜混浊/病理学角膜混浊/预防和控制二氯酚酸/投药和剂量疾病模型动物激光准分子眼药水屈光性角膜切削术手术后并发症/预防和控制伤口愈合/药物作用动物男(雄)性兔

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CORTICOSTEROIDS AND THYROID-FUNCTION - DIFFERENT EFFECTS ON PLASMA-VOLUME, THYROID-HORMONES AND THYROID HORMONE-BINDING PROTEINS AFTER ORAL AND INTRAVENOUS ADMINISTRATION

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ACTA MEDICA SCANDINAVICA 1979年第5期205卷 379-383页

作者： GAMSTEDT, A JARNEROT, G KAGEDAL, B SODERHOLM, B REG HOSP OREBRO DEPT CLIN PHYSIOL OREBRO SWEDEN REG HOSP LINKOPING DEPT CLIN CHEM LINKOPING SWEDEN

The influence of glucocorticosteroids on plasma volume, thyroid hormones and thyroid hormone-binding proteins was studied in 17 patients. Plasma volume was not affected either by i.v. .beta.-methasone (6 mg daily) or by oral prednisolone (45-180 mg daily) given for 5 days. The serum T3 [triiodothyronine] concentration decreased while r[reverse]T3 increased independently of the route of administration of corticosteroids. Serum T4 [thyroxine] concentration decreased after i.v. but not after oral administration of corticosteroids. Oral steroids as compared to i.v. increased the 125I-T3 uptake test value. The serum TBG [thyroxine binding globulin] concentration decreased independently of the route of administration, while the serum TBPA [thyroxine binding prealbumin] concentration increased after oral corticosteroids but was unchanged after i.v. treatment. The serum TSH concentration was slightly reduced. About half of the patients were given both corticosteroids and nutrition i.v. and the other half were given all treatment orally. The part played by the route of administration of corticosteroids and calories, respectively, cannot be evaluated at present but these factors seem to be of importance.

关键词：投药口服倍他米松/投药和剂量倍他米松/药理学注射静脉内血浆容量/药物作用泼尼松龙/投药和剂量泼尼松龙/药理学血清球蛋白类/分析甲状腺功能试验甲状腺激素类/血液促甲状腺素/血液甲状腺素/血液甲状腺素结合蛋白质类/分析三碘甲状腺原氨酸/血液三碘甲状腺原氨酸逆转/血液成年人老年人女(雌)性人类男(雄)性中年人

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