Salivary theophylline estimation in the management of asthma in children.

Simultaneous sampling was performed to determine whether saliva could replace plasma in the monitoring of theophylline dosages. Forty-eight children with moderate to severe asthma received oral theophylline preparation (usually sustained release) on a daily basis. They provided simultaneous saliva and plasma samples at routine out-patient visits. Saliva and plasma theophylline concentrations showed a wide variation between individuals, and their ratios also differed. Saliva theophylline concentrations below 7 micrograms/ml reflect plasma concentrations below 10 micrograms/ml, i.e. sub-therapeutic, while saliva concentrations above 7 micrograms/ml are consistent with therapeutic dosage. Estimation of saliva theophylline concentration on routine visits avoids the discomfort of blood sampling. It reflects whether daily oral theophylline dosage in childhood asthma is below or within the therapeutic range. The need for changes in dosage and the degree of patient-compliance with therapy can be usefully indicated.     

RADIOIMMUNOASSAY OF SALIVARY CORTISOL AND ITSCLINICAL APPLICATIONS

The measuremeiit of salivary cortisol (F) wasaccomplished by using tritium labeled F. Comparison between saliva cortisol concentrations in matched samples collected with or without stimulation of citric acid indicated that salivary cortisol concentration is independent of salivary flow rate. In 104 normal subjects, average salivary cortisol value was 3.15 ng/ml with no significant sex difference. The ratio of saliva cortisol to plasma cortisol was 3.070. The oomparative circadian variations in saliva and plasma cortisol levels were examined and samples collected every 4 hours throughout a 24hour cycle. The result indicated that the levels of salivary cortisol parallelled tho:.e of plasma cortisol. After ACTH stimulation the cortisol response of 6 control subjects was greater in the saliva than in the plasma. 90 minutes after intramuscular ACTH injection the cor tisol level was 4.&fold the basal in saliva, compared with l.&fold in plasma. After eight hour ACTH tn- traavenous infusion the cortisol level increased by 8.6 fold in the saliva, compared with 3.4-fold in the plasma. Cortisol level suppression was also more pro- nounced in the saliva (9070) than in the plasma (8570) after 0.75 mg dexamethasons administration. In 13 control subjects the average salivary cortisol level of 6 measurements throughout a 24-hour cycle was l.36 ng/ml, whereas in 12 cases of Cushing's syndrome this reached 9.1 ng/ml and in 2 cases of Addison's disease it was only 0.14 and 0.52 ng/ml. In 105pregnant women total serum cortisol concentration was markedly increased, but salivary cortisol level was within the normal range of nonpregnant wDmen.     

茶碱微乳经皮吸收及药代动力学研究

目的：研究茶碱微乳在家兔不同皮肤部位给药后的经皮吸收及药代动力学。方法：采用HPLC测定血浆中茶碱的浓度,应用基于Guass-Newton-Zhu原理设计的NLFTZ计算机程序对实验数据进行解析。结果：茶碱微乳经背部肺腧穴给药后的血药浓度高于非穴位给药,有极显著性差异（P〈0．01）;茶碱经皮吸收符合两个独立的具不同时滞的零级吸收、一级消除的一室模型迭加形成的复合模型,血药浓度平稳,可以维持24h以上。结论：茶碱微乳经皮吸收均具有双通道、双过程复合的特征;穴位经皮给药的两种通道中存在特殊的加速通道,而药物经穴位周围皮肤的穿透表现为慢吸收过程。     

白三烯B4在慢性阻塞性肺疾病中的变化与氨茶碱对其的影响

目的:探讨白三烯B4(1eukotriene B4,LTB4)在慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)气道局部与血循环中的变化与氨茶碱对其影响.方法:32只雄性Wistar大鼠按随机数字表法分成A组(正常对照组)、B组(COPD组)、C组(氨茶碱低剂量组)、D组(氨茶碱高剂量组),每组8只.测定各组大鼠肺功能,观察肺组织病理改变,对支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)行细胞计数与分类,并检测BALF、血浆及肺组织匀浆液中白细胞介素-8(IL-8)、LTB4的水平.结果:COPD大鼠BALF中LTB4水平较正常对照组明显增高,并与中性粒细胞百分比(r=0.794,P=0.007)、IL-8水平呈显著正相关(r=0.863;P=0.012),与呼气峰流速(peak expiratoryflow,PEF)呈显著负相关(r=-0.718,P=0.028),并与小气道病变中的炎症细胞浸润评分显著正相关(r=0.836,P=0.036).氨茶碱的干预可降低COPD大鼠BALF中LTB4水平及中性粒细胞%,改善小气道黏液细胞渗出,杯状细胞化生,炎症细胞浸润,纤维结缔组织增生,平滑肌增生等各项病理评分及病理总分,其中,对杯状细胞化生,炎症细胞浸润的作用在高剂量组更明显.氨茶碱对PEF无明显改善.结论:LTB4在COPD疾病中表达水平增高,参与气道炎症过程.氨茶碱的治疗可降低COPD大鼠BALF中LTB4水平以及中性粒细胞%,改善小气道病变.     

Total antioxidant capacity and levels of epidermal growth factor and nitric oxide in blood and saliva of insulin-dependent diabetic patients

BACKGROUND: The aim of this study was to examine how type 1 diabetic patients have altered levels of lipid peroxidation, antioxidant defense, NO and EGF in their plasma and saliva. We tested the differences in lipid peroxidation level, antioxidant power, and concentrations of epidermal growth factor (EGF) and nitric oxide (NO) in saliva and blood of type 1 diabetic subjects in comparison to healthy control subjects. METHODS: Nineteen subjects with type 1 diabetes mellitus and 19 healthy age- and sex-matched control subjects were included in the study. Blood and saliva samples were obtained and analyzed for thiobarbituric reactive substances (TBARS) as a marker of lipid peroxidation, ferric reducing ability (total antioxidant power), EGF and NO levels. RESULTS: TBARS levels did not show a significant difference between the two groups. Analysis of antioxidant power revealed that saliva and plasma of diabetic patients had more antioxidant power (p <0.01) than the healthy control population (107 +/- 10.35 vs. 11.14 +/- 4.66 and 192 +/- 12.3 vs. 142 +/- 15.2 mmol/L, respectively). Concentration of EGF was increased (p <0.01) in saliva whereas it was reduced (p <0.01) in plasma of diabetic patients in comparison to those of healthy subjects (2423 +/- 322 vs. 1513 +/- 341 and 125 +/- 14 vs. 346 +/- 60 pg/mL, respectively). NO level increased in both saliva and plasma of diabetic patients in comparison to those of healthy subjects (46.61 +/- 7 vs. 72.89 +/- 13 and 62.11 +/- 4.6 vs. 76.25 +/- 5 micromol/L, respectively). Blood HbA1c (%) of patients was significantly higher than that of controls (8.3 +/- 0.32 vs. 5.4 +/- 0.24, p <0.01). CONCLUSIONS: Existence of increased total antioxidant power in the presence of normal lipid peroxidation in plasma and saliva of type 1 diabetic patients indicates the existence of oxidative stress. Increased salivary EGF and NO levels in association with elevated TAOP is interesting and should be further studied.     

Increasing saliva (free) oestriol to progesterone ratio in late pregnancy: a role for oestriol in initiating spontaneous labour in man?

Oestriol and progesterone concentrations were measured in samples of saliva obtained daily from six normal women during the final four weeks before the spontaneous onset of labour. Progesterone concentrations were found to plateau whereas oestriol concentrations continued to rise so that the mean ratio of saliva oestriol to progesterone increased from 0.80 to 1.43 between 29 days and one day before labour. Saliva oestriol concentrations were 15 times higher than saliva oestradiol concentrations. As saliva steroid concentrations reflect the unbound unconjugated (free) plasma steroid concentrations these data suggest that a changing ratio of oestriol to progesterone may play a part in initiating spontaneous labour in man.     

Serum theophylline concentrations during multiple dosing with two sustained release methylxanthine preparations in normal subjects.

In normal subjects, receiving multiple dosing regimens with Slophyllin and Phyllocontin in does calculated to give either 4 mg/kg or 6mg/kg theophylline free acid twice daily, serum theophylline concentrations were frequently less than 8 mg/l. Accumulation of the serum theophylline trough concentration occurred during the first 3 days of multiple dosing, and was followed by subsequent stabilization or even decline in serum theophylline trough concentrations. Side effects were noted with both Slophyllin and Phyllocontin, but only on the higher dosage regimens; they occurred within 24--48 hr of starting the drug, and tended to diminish if dosing was continued. The accumulation effect of serum theophylline concentrations may explain the timing of adverse effects, and should be avoided by starting methylxanthine therapy at a low dose. This may be increased after a few days. Further dosage adjustment may be necessary in some patients and should be facilitated by measurement of serum theophylline trough concentrations.     

加替沙星对人体长效茶碱血清浓度影响的研究

目的:观察加替沙星对人体内茶碱血清浓度有无影响。方法:采用荧光偏振免疫法(FPIA),测定8例COPD患者在长效茶碱单用及与加替沙星合用后的茶碱血清浓度,并对两组数据进行统计学分析。结果:长效茶碱与加替沙星合用前后患者的茶碱血清浓度变化无统计学意义(P>0.05)。结论:加替沙星对人体茶碱血清浓度影响不大,与茶碱合用是安全的。     

唾液与血清肾功能检测指标的相关性

目的 通过检测唾液与血清中肾功能指标的相应数据，从中探讨其相关性，为临床提供一条肾功能检查的新逢径，方法 对54例患者于同日清晨采集唾液与血清并同步进行UN，CRE，HCO3^-，K^＋，GLU检测，然后进行唾液与血清检测指标的相关性分析，并进行统计学处理。结果 唾液与血清UN，CRE有显著相关性（r=0．957，P〈0．01；r=0．929，P〈0．01）．HCO3^-，K^＋，GLU无相关性（P〉0．05）．结论 唾液中UN,CRE的检测数据可以作为评价肾功能的指标应用于临床。     

血液与唾液中苯巴比妥浓度之间相关性的研究

目的:用HPLC法测定癫痫患者血液与唾液中苯巴比妥的浓度,对两者之间的相关性进行研究,考查是否可以在临床药物监测中用唾液代替血液作为检测样本。方法:测定癫痫患者血液与唾液中苯巴比妥的浓度,采用数理统计的方法对两者之间的相关性进行研究。结果:血液与唾液中苯巴比妥浓度之间具有良好的相关性.结论:在临床药物监测中,可以用唾液代替血液作为检测样本。     

Plasma and salivary concentrations of erythromycin after administration of three different formulations.

In a 6-volunteer cross-over study the pharmacokinetics of 3 erythromycin preparations were compared. A single oral dose of 500 mg of each preparation was administered at each occasion and the levels measured in timed samples of plasma and saliva. Markedly higher blood concentrations of the estolate and propionate were obtained compared to the stearate. Comparison of serum and plasma concentration of the drugs from each split sample showed no significant differences. Plasma concentrations always exceeded those in saliva but for any one preparation a similar ratio was obtained at different times. This may be useful to ascertain compliance and to measure concentration of the compounds where direct measurement in plasma is not practicable.     

乳酸卡德沙星对大鼠肝P450酶活性的影响

目的:研究乳酸卡德沙星对大鼠肝P450酶活性的影响。方法:采用鸡尾酒技术,测定单剂量和多剂量使用乳酸卡德沙星前后大鼠血浆中相应的探针药物咪达唑仑、右美沙芬、奥美拉唑、茶碱、氯唑沙腙和双氯芬酸的浓度及其药代动力学参数。结果:大鼠单剂量给予乳酸卡德沙星后,探针药物的浓度及其药代动力学参数均没有显著性变化。按每天两次,每次9 mg/kg剂量灌胃乳酸卡德沙星,连续12 d后,与用药前比较,咪达唑仑和双氯芬酸的血药浓度及其药代动力学参数未见显著性改变;但奥美拉唑的血药浓度及其AUC0-t有升高的趋势,茶碱的血药浓度及其AUC0-t有降低趋势;右美沙芬的血药浓度和AUC0-t显著升高,而氯唑沙腙的血药浓度和AUC0-t显著降低。结论:单剂量使用乳酸卡德沙星对探针药物的药代动力学行为没有显著性影响。多剂量给予乳酸卡德沙星对大鼠代谢氯唑沙腙的代谢酶有诱导作用,对代谢右美沙芬的代谢酶有抑制作用。     

Phenytoin-valproate interaction: importance of saliva monitoring in epilepsy

Sodium valproate is often used with phenytoin when epilepsy cannot be controlled by a single drug. Sodium valproate depresses phenytoin protein binding and so invalidates plasma phenytoin monitoring as a means of determining precise phenytoin dosage requirements. Plasma and saliva phenytoin and plasma valproate concentrations were measured in 42 patients with epilepsy receiving both drugs. Phenytoin protein binding was also measured by ultrafiltration in 19 of these patients and 19 patients taking phenytoin alone. Saliva phenytoin concentration bore the same close correlation to unbound (therapeutically active) phenytoin in patients receiving both drugs as it did in patients receiving phenytoin alone, whereas plasma total phenytoin did not. The same therapeutic range for saliva phenytoin (4-9 mumol/1; 1-2 microgram/ml) was therefore valid in both groups. The depression of phenytoin binding was directly related to the plasma concentration of valproate both in random samples taken from the 42 patients and in samples taken throughout the day in two of these patients. This was confirmed in vitro. Even when the concentration of valproate is known the degree of binding cannot be predicted. Saliva rather than plasma monitoring of phenytoin treatment is therefore valuable in the presence of valproate and with reduced phenytoin binding from any cause.     

生物体液中美多洛尔和α-羟基美多洛尔反相离子对HPLC测定

建立了同时测定人血浆、唾液和尿液中美多洛尔及其代谢物α-羟基美多洛尔的反相离子对高效液相色谱-紫外检测法。本法回收率≥92%,色谱分离效果好,而层析时间<10min,并有较高的特异性、重复性及精密度,日间及日内测定的变异系数≤6.3%。美多洛尔和α-羟基美多洛尔在上述体液中的最低检测限,除血浆中α-羟基美多洛尔为50ng/ml外,余均为10ng/ml。无论用外标法还是以普萘洛尔为内标物的内标法定量,在0.1-10μg/ml范围内,美多洛尔和α-羟基美多洛尔均有良好的线性关系     

使用含氟漱口液和APF溶液后菌斑和唾液氟离子水平的动态观察

目的 :测定正常人使用含氟漱口液和 APF溶液后 ,唾液及菌斑中氟离子浓度 ,并探讨其对龋病预防的意义。方法 :选择 40例自愿者 ,用离子选择性氟电极测定单独使用含氟漱口液 ( A组 )及联合使用含氟漱口液和 APF溶液后 ( B组 )不同时间点氟浓度 ,并与基线水平相比较。结果 :B组在用氟后 60 min内唾液和菌斑氟浓度都较基线水平有显著性提高( P<0 .0 5 ) ,A组只在 2～ 5 min时高于基线水平。 A组与 B组相比 ,各个时间点唾液和菌斑氟浓度差异无显著性。结论 :联合使用含氟漱口液和 APF溶液后可以使菌斑和唾液的氟浓度升高 60 min左右 ,多种剂型和途径联合用氟是较为有效的氟防龋方法。     

高血浓度茶碱致心律失常的临床观察

目的：观察高血浓度茶碱对心律失常的影响,探索安全合理使用茶碱方法。方法：收集１９４例住院治疗的病例,测定其血液茶碱浓度及作心电图检查,并按血浓度分为高浓度组（Ａ组）和治疗浓度组（Ｂ组）,同时选择５６例未使用氨茶碱作对照组（Ｃ组）。结果：Ａ组及Ｂ组引起窦性心动过速发生率分别为５７．７％、３９．８５％,房纤及房扑发生率分别是４４．４％、２．１５％,房性早搏发生率分别为４４．４％、４．３０％,室性早搏     

Treatment of breast proliferation disease with modified xiao yao san and er chen decoction

The authors report the 3 months' treatment of 51 cases of breast proliferation disease with modified Xiao Yao San and Er Chen decoction, an effective rate being 96.1%. In each patient before and after treatment, saliva estradiol (SE2), saliva progesterone (SP), saliva testosterone (ST) and plasma prolactin (PRL) concentrations were monitored and breast molybdenum-target X-ray films were taken. The results showed that after treatment, SE2 concentrations declined very significantly (P less than 0.001); SP concentrations declined significantly (P less than 0.05); PRL concentrations declined very significantly (P less than 0.005), but ST concentrations did not change significantly. Breast molybdenum-target X-ray films showed absorption of proliferation masses in 21 cases. These indicated that the medicine could regulate endocrine system, perhaps through suppressing secretion of PRL, decreasing prolactin antagonist action to follicular stimulating hormone so as to restore follicle function, and could regulate pituitary-follicle axis and make the axis normal.     

254例中国癫痫患者丙戊酸和2-丙基-4-戊烯酸浓度与不良反应的相关性

目的：分析丙戊酸(valproic acid,VPA)及其毒性代谢物2-丙基-4-戊烯酸(2-propyl-4-pentenoic acid,4-ene-VPA)的血药浓度与二者所致不良反应的相关性,为临床安全合理使用VPA提供依据。方法：收集中南大学湘雅医院门诊确诊为癫痫,且长期服用丙戊酸钠口服溶液单药或者合并用药的254例患者,采用气相层析-质谱联用法测定血中VPA和4-ene-VPA浓度,采用双变量相关分析对血中VPA和4-ene-VPA浓度与所致不良反应的关系进行分析。结果：血小板(PLT)数量与VPA给药剂量呈显著负相关(P<0.01和P<0.05),红细胞(RBC)数量与VPA浓度呈显著负相关(P<0.01);合并用药组中4-ene-VPA,VPA,谷丙转氨酶(ALT)和谷草转氨酶(AST)均显著高于单药组(P<0.05);在单药组中≤2岁患者组ALT和AST显著高于>2岁患者组(P<0.001);在合并用药组中,≤2岁患者组AST,WBC和PLT水平同样显著高于>2岁 患者组(P<0.05)。AST与4-ene-VPA和VPA浓度之间不相关(分别为r=0.031,r=0.035,P>0.05),ALT水平与4-ene-VPA和VPA浓度之间亦不相关(分别为r=–0.064,r=–0.089,P>0.05)。结论：VPA可能影响血常规指标,年龄、合并其他非肝药酶诱导抗癫痫药是VPA相关肝肾功能异常的危险因素,血中VPA及4-ene-VPA浓度监测不适合预警丙戊酸所致的肝毒性。     

小剂量茶碱对大鼠气道平滑肌细胞表达NF-κB与ICAM-1的影响

目的:观察小剂量茶碱对培养的大鼠气道平滑肌细胞表达核因子κB(NF-κB)与细胞间黏附分子1(ICAM-1)的影响,探讨小剂量茶碱在气道发挥抗炎作用的可能机制。方法:体外培养正常大鼠鼠婴的气道平滑肌细胞,将培养出的细胞随机分为3组:空白对照组、肿瘤坏死因子α(TNF-α)刺激组、茶碱干预组。采用免疫组织化学SP法检测经TNF-α刺激的大鼠的气道平滑肌细胞中加入不同浓度的茶碱共同培养4 h,以及加入同一浓度茶碱共同培养不同时间,NF-κB活性和ICAM-1表达的变化。结果:TNF-α刺激组与空白对照组的NF-κB活性和ICAM-1表达相比较,差异均有显著性(P<0.05)。经TNF-α刺激的大鼠的气道平滑肌细胞中加入5,10,15 mg/L的茶碱共同培养4 h,NF-κB活性和ICAM-1表达均有所下降。与TNF-α刺激组相比,5 mg/L组无统计学差异(P>0.05),余两组差异均有显著性(P<0.05)。且茶碱干预组内两两比较,差异均有显著性(P<0.05)。经TNF-α刺激的大鼠的气道平滑肌细胞中加入10 mg/L茶碱共同培养2,4,24 h。与TNF-α刺激组相比,茶碱处理组的差异均有显著性(P<0.05)。但茶碱处理组内不同处理时间两两比较,差异无显著性(P>0.05)。结论:茶碱可能通过抑制气道平滑肌细胞NF-κB活性和ICAM-1的表达,进而减少炎症细胞在气道的浸润。     

家兔中盐酸多西环素缓释凝胶牙龈给药与口服给药的比较

目的比较盐酸多西环素注入用缓释凝胶局部牙龈给药与口服给药的优劣。方法分别给家兔口服市售盐酸多西环素片和牙龈注射盐酸多西环素缓释凝胶作自身对照,用高效液相色谱法分别测定两种给药方式的唾药浓度和血药浓度。结果牙龈注射给药时唾药浓度远高于口服给药,而后者血药浓度亦高于前者。结论盐酸多西环素缓释凝胶治疗牙周炎的效果优于口服片剂。