Topical Fat Reduction

The fat on women's thighs is more difficult to mobilize due to increased α-2 adrenergic receptor activity induced by estrogen. Lipolysis can be initiated through adipocyte receptor stimulation (β adrenergic) or inhibition (adenosine or α-2 adrenergic) or by inhibition of phosphodiesterase. Since many women desire regional thigh fat loss, a series of clinical trials were initiated using one thigh as a double-blinded control. Trial #1: Five overweight women had injections of isoproterenol at intervals around the thigh three times a week for 4 weeks with diet and walking. Trial #2: Five overweight woman had ointment containing forskolin, yohimbine and aminophylline applied to the thigh five times a week for 4 weeks after hypertonic warm soaks with a diet and walking. Trial #3: Eighteen overweight women were divided into three groups of six and trial #2 was repeated with each agent alone vs. placebo using forskolin, yohimbine or aminophylline in separate ointments. Trial #4: Thirty overweight women had 10% aminophylline ointment applied to the thigh five times a week for 6 weeks with diet and walking. Chemistry panel, theophylline level and patch testing wereperformed. Trial#5: Twelve women had trial #4 repeated with 2% aminophylline cream without a diet or walking. Trial #6: Trial #5 was repeated with 0.5% aminophylline cream. All trials except yohimbine ointment gave significantly more girth loss from the treated thigh (p < 0.05 to p < 0.001). Chemistry panel showed no toxicity. Theophylline was undetectable and patch testing was negative. We conclude that topical fat reduction for women's thighs can be achieved without diet or exercise.     

Inhibition of elongation and H+ and K+ transport by the phosphodiesterase inhibitor aminophylline in plant tissue

Aminophylline, an inhibitor of cyclic nucleotide phosphodiesterase (EC 3.1.4.17), inhibits elongation and correlated H⁺ and K⁺ transport in embryos of Haplopappus gracilis and in pea internode segments. Moreover, the drug strongly inhibits the stimulation of these processes by fusicoccin and indole-3-acetic acid and reduces passive permeability of the membrane. The possible mechanisms of action of aminophylline are discussed.Abbreviations cAMP adenosine 3:5-cyclic monophosphate - FC fusicoccin - IAA indole-3-acetic acid - MES 2-N-morpholinoethanesulfonic acid - PDE cyclic nucleotide phosphodiesterase     

脑室注射氨茶碱或咪唑对大鼠电针镇痛的影响

我们曾经报道,给大鼠脑室注射 cAMP,外源性地提高脑内 cAMP 水平,引起大鼠的电针镇痛效应显著减弱,并有明显的剂量效应关系。已知裂解 cAMP 的磷酸二酯酶(PDE)抑制剂茶碱能提高脑内 cAMP 含量,而 PDE 激活剂咪唑则能降低脑内 cAMP 水平。因此本文用脑室注射 PDE 抑制剂氨茶碱或 PDE 激活剂咪唑的方法以图改变中枢内源性 cAMP 的水平时对电针镇痛的影响。结果表明氨茶碱能拮抗电针镇痛,而咪唑则对电针镇痛有加强作用。这与外源性注射 cAMP 的结果一致,说明脑内 cAMP 可能是对抗电针镇痛的一个重要因素。     

人外周血T淋巴细胞凋亡与胀亡研究及氨茶碱的诱导作用

目的:在前期研究的基础上进一步观察氨茶碱对人外周血T淋巴细胞凋亡与胀亡的诱导作用。方法:密度梯度离心法及尼龙棉柱法分离健康成年人外周血T淋巴细胞,分空白组及氨茶碱组,培养后观察细胞光镜及电镜形态学、FDA/PI荧光染色,并用流式细胞仪检测凋亡和胀亡细胞比例变化。结果:①人外周血T淋巴细胞经体外培养,可自然出现典型的细胞凋亡与胀亡形态学改变。②人外周血T淋巴细胞在氨茶碱诱导作用下,凋亡率有显著增高,但胀亡率相对无显著增高。结论:人外周血T淋巴细胞存在凋亡与胀亡现象,氨茶碱可诱导人外周血T淋巴细胞凋亡,但不能有效的诱导健康人外周血T淋巴细胞胀亡。     

氨茶碱及硝苯吡啶治疗高原肺水肿效果观察

目的:评价氨茶碱及硝苯吡啶对高原肺水肿的疗效.方法:采用右心漂浮导管方法,观察了静脉推注氨茶碱及舌下含服硝苯吡啶对患者血流动力学及动脉血气等方面的影响.结果:氨茶碱能降低患者的肺动脉压和肺血管阻力,提高患者的心输出量及动脉血氧饱和度,用药前后体循环压及心率未见明显变化.硝苯吡啶含服也能降低肺动脉压和肺血管阻力,虽能降低体循环压但幅度较小,但用药前后心输出量、心率及动脉血气饱和度未见明显变化.结论:氨茶碱及硝苯吡啶均有急性降低高原肺水肿患者肺动脉高压的作用,但二者相比,氨茶碱降低肺动脉压效果明显优于硝苯吡啶.     

Adenosinergic Modulation of Ventilation in Obese Zucker Rats

Objectives: The goal of our study was to determine whether altered adenosinergic mechanisms contribute to the depressed ventilatory response observed in obese Zucker rats. Research Methods and Procedures: Eight lean and eight obese Zucker rats were studied at 7 to 8 weeks of age. Ventilation (V˙_E) during room air, during 5‐minute hypercapnic (7% CO₂, balance O₂), and during 30‐minute sustained hypoxic (10% O₂) exposures were sequentially measured by the barometric method on three separate occasions after the randomized blinded administration of equal volumes of either saline (control), 8‐(p‐sulfophenyl)‐theophylline (8‐PST, 7 mg/kg, peripheral adenosine antagonist), or aminophylline (AMPH, 15 mg/kg, peripheral and central adenosine antagonist). Results: During room air and hypercapnic exposures, AMPH (but not 8‐PST) significantly (p < 0.05) increased V˙_E in both lean and obese rats. During acute (2 minute) hypoxic exposure, 8‐PST (but not AMPH) significantly depressed V˙_E in lean rats. In contrast, AMPH (but not 8‐PST) selectively increased V˙_E in obese rats. During sustained (10 to 30 minutes) hypoxic exposure, neither AMPH nor 8‐PST administration altered V˙_E in lean rats. In contrast, AMPH (but not 8‐PST) selectively increased V˙_E during the late response in obese rats. Discussion: Our findings indicate that obese rats possess altered adenosinergic modulation of ventilatory responses to acute and sustained hypoxia in two opposite ways. We conclude that the reduced hypoxic ventilatory response observed in obese Zucker rats is attributed to depressed adenosinergic peripheral excitatory mechanisms and to enhanced adenosinergic central depression mechanisms, both of which contribute to the blunted ventilatory response in obesity.     

Chrono-Optimization of the Time of Evening Administration with Unequally Divided Twice-Daily Theophylline

The effect of different times of evening administration (2000 hr versus 2200 hr) of sustained-release aminophylline (Euphyllin®CR) on pharmacokinetics and lung function was investigated in 30 patients presenting with moderately severe asthma. The study protocol followed a randomized three-period change-over design including a placebo period. As the dosing of the investigated SR-formulation is circadian rhythm adapted, the major part of the daily dose, namely 2/3, is affected by the change in time of administration. With regard to the nocturnal peak expiratory flow (PEF), no statistically significant difference between the times of evening administration was detected. However, the concomitant requirement for corticosteroids and inhaled beta-2-mimerics complicates the assessment of the relative clinical efficacy of the major dosing of theophylline during the 24 hr even though this drug is usually not given as a monotherapy in severe patients with reversible airway obstruction.     

串脉冲致兔隔肌疲劳的动物模型

本实验采用串脉冲刺激兔隔神经法复制了家兔膈肌疲劳模型。测定隔肌张力（Ｔｄｉ）、跨膈压（Ｐｄｉ）及其频率特性（Ｔｄｉ－Ｆ、Ｐｄｉ－Ｆ）、呼吸流速（Ｖ）、肺阻力（ＲＬ）、膈肌肌电图（ＥＭＧｄｉ等作为评价膈肌收缩力量的指标。结果发现：经串脉冲刺激后,Ｐｄｉ－Ｆ曲线在３０、５０和１００Ｈｚ时显著降低,Ｐｄｉ、Ｔｄｉ、Ｖ和跨肺压均显著下降。氨茶碱可增加隔肌收缩力,延缓膈肌疲劳过程。结果提示,用串脉冲刺激兔膈神经法建立的模型是一种灵敏、可靠和稳定的膈肌疲劳动物模型。     

氨茶碱,环磷酸泉苷葡甲胺（MCA）对兔膈肌功能的影响

目的：观察氨茶碱、环磷酸腺苷葡甲胺对兔跨膈压及膈肌电活动的影响,以中肌疲劳的治疗效果提供实难依据。方法：刺激双侧膈神经４０ｍｉｎ复制膈肌疲劳（ＤｉＦ）动物模型,动物随机分三组（ｎ＝６）：氨茶碱组（１０ｍｇ／ｋｇ）、ＭＣＡ组（１０ｍｇ／ｋｇ）,合用组（氨茶碱１０ｍｇ／ｋｇ＋葡甲胺ｃＡＭＰ（１０ｍｇ／ｋｇ）。于ＤｉＦ前、ＤｉＦ及给药后３０、６０ｍｉｎ记录中压（Ｐｄｉ）;记录膈肌肌电图（ＥＭＧｄｉ）并输     

P物质对大鼠胃窦肌条收缩活动的影响及其机制探讨

本文利用器官浴槽孵育离体大鼠胃窦肌条,观察Ｐ物质（ｓｕｂｓｔａｎｃｅＰ,ＳＰ）对肌条收缩的效应及多种拮抗剂或抑制剂对ＳＰ效应的影响。结果：（１）ＳＰ明显增强肌条收缩幅度,在剂量为８×１０－１１－８×１０－７ｍｏｌ范围内里剂量－效应关系。ＳＰ４×１０－８ｍｏｌ,使肌条收缩幅度增强１６０．９±２３．０％．与生理盐水组比较Ｐ＜０．００１。（２）神经节阻断剂六烃季胺、５－ＨＴ２受体阻断剂赛庚啶、Ｈ１受体阻断剂苯海拉明、磷酸二酯酶抑制剂氨茶碱使ＳＰ肌条收缩幅度增强效应明显减弱（Ｐ＜０．０５）。（３）阿托品、心得安、酚妥拉明、氟哌啶醇和纳洛酮预孵育后,ＳＰ增强收缩幅度的效应与单独ＳＰ组相比差异无显著性。结果提示ＳＰ可能是肠神经系统中的非胆碱能兴奋性递质,可能通过激活５－ＨＴ神经元、促使组织胺释放等途径而增强肌条的收缩幅度。