成年人活动性肺结核患者血清腺苷脱氨酶和降钙素原联合检测的临床意义

目的：探讨成年人活动性肺结核患者血清腺苷脱氨酶（ ADA）和降钙素原（ PCT）检测的临床意义。方法选择81例活动性肺结核患者作为A组、非结核性肺部感染患者43例作为B组、肺癌患者27例作为C组。测定三组患者血清ADA和PCT,并对结核患者进行6个月的抗痨治疗。结果 ADA水平：A组与B、C组差异均有统计学意义（t＝12．983、10．630,均P＜0．01）,B组与C组差异无统计学意义（t＝0．144,P＝0．885）;PCT水平：A组与B组差异有统计学意义（t＝16．775,P＜0．01）,A组与C组差异无统计学意义（t＝1．571,P＝0．119）,B组与C组差异有统计学意义（t＝11．235,P＜0．01）。81例肺结核患者经治疗后缓解67例,无缓解14例;缓解组患者血清ADA和PCT水平均明显低于无缓解组患者（ t＝3．087、3．404,均P＜0.05）。结论血清ADA可以作为活动性肺结核的诊断指标,ADA和PCT联合测定可以判断活动性肺结核的预后。     

联合检测乳酸脱氢酶和腺苷脱氨酶对结核性胸腔积液的诊断价值

目的探讨联合检测乳酸脱氢酶(LDH)和腺苷脱氨酶(ADA)对结核性胸腔积液的诊断价值。方法 186例胸腔积液患者分为结核组75例和非结核组111例,分别进行血浆和胸腔积液LDH和ADA检测。结果结核组血浆和胸腔积液LDH及ADA水平均高于非结核组,差异均有统计学意义(P<0.05)。结论血清和胸腔积液LDH、ADA联合检测,对临床结核性胸膜炎的诊断具有较高价值。     

支气管肺泡灌洗液腺苷脱氨酶检测在痰菌阴性肺结核诊断中的应用

目的：探讨支气管肺泡灌洗液中腺苷脱氨酶浓度对痰涂片抗酸杆菌阴性肺结核的诊断价值。方法64例菌阴肺结核患者和肺结核组、正常对照组的 BALF 同时检测 ADA、罗氏培养法和 PCR 法检测结核分枝杆菌,并比较分析。结果痰菌阴性的肺结核组患者 BALF 中的 ADA 含量明显高于非结核组（t＇＝11．2587,t＇α＝1．9986,P ＜0．05）;而与痰菌阳性组相比无统计学意义。菌阴肺结核 BALF 中 ADA 的阳性率与 TB DNA PCR 法比较无统计学意义,而显著高于罗氏培养法。结论对菌阴肺结核支气管肺泡灌洗液中 ADA 浓度进行测定有较高的诊断和鉴别诊断价值,是一种简单有效低廉快速的临床应用方法。     

Safety evaluation of AMP deaminase from Aspergillus oryzae

Adenosine-5′-monophosphate (AMP) deaminase is an enzyme used to increase concentrations of 5’-inosine monophosphate in certain foods and beverages for flavoring purposes. One commercial source of this enzyme is Aspergillus oryzae, a filamentous fungus with a history of safe use in Asia as a fermentation organism used in the production of miso sauce and sake liquors. Noting the use of the enzyme in food intended for human consumption and potential presence at trace levels in finished goods, a series of safety studies including an in vitro Ames test and chromosome aberration assay with Chinese hamster lung fibroblasts were conducted along with a 90-day oral toxicity study in rats. AMP deaminase showed no evidence of genotoxicity in the in vitro tests. Following gavage administration of Sprague–Dawley rats at dosages of 19.8, 198.4, or 1984 mg total organic solids (TOS)/kg body weight (bw)/day for 90 days, no adverse effects on body weight gain, food consumption, hematology, clinical chemistry, urinalysis, ophthalmological and histopathological examinations were observed. The no-observed-adverse-effect level was considered to be 1984 mg TOS/kg bw/day, the highest dose tested. Results of the genotoxicity studies and subchronic rat study support the safe use of AMP deaminase produced from A. oryzae in food production.     

AMP579与腺苷对大鼠心室肌细胞Na~+/Ca~(2+)交换电流作用的比较(英文)

目的阐明AMP579与腺苷不同药理作用与临床效果的机制。方法采用全细胞膜片钳记录Na+/Ca2 +交换电流。结果AMP579对Na+/Ca2 +交换的外向和内向电流均呈浓度依赖性增强。灌流腺苷A1受体阻断剂PD116948 30μmol·L-1,A2受体阻断剂DMPX10μmol·L-1,蛋白激酶A特异阻断剂KT5720 0 .2μmol·L-1或蛋白激酶C特异阻断剂GF109203X0 .4μmol·L-1对AMP579 Na+/Ca2 +交换电流的激动作用均无影响,提示AMP579对Na+/Ca2 +交换电流具有直接的激动作用。结论AMP579对Na+/Ca2 +交换电流可能具有直接的激动作用。     

结核性胸膜炎腺苷脱氨酶活性低表达与喹诺酮类的相关性

目的:探讨结核性胸膜炎腺苷脱氨酶活性低表达与喹诺酮类的相关性。方法:对我科2006年1月-2009年3月确诊为结核性胸膜炎的83例病人进行回顾性研究,以胸水ADA<45u/l为观察组33例,胸水ADA>45u/l为对照组50例,起病前1周至抽胸水前使用过喹诺酮类药物为暴露因素,比较两组暴露的差异。结果:观察组有喹诺酮类应用史者20例,无喹诺酮类应用史者13例,对照组有喹诺酮类应用史者5例,无喹诺酮类应用史者45例,两组暴露比较χ2=22.77,P<0.001,OR=13.85。结论:结核性胸膜炎腺苷脱氨酶活性低表达与近期应用喹诺酮类有关,且相关性强,对诊断未明胸腔积液患者,在诊断明确前,因尽量避免应用喹诺酮类药物。     

Modifications of deoxycytidine kinase and deaminase activities by docosahexaenoic acid in normal and transformed rat fibroblasts

Deoxycytidine kinase (dCK) and deoxycytidine deaminase (dCDA) are two key enzymes in the activation and inactivation, respectively, of deoxycytidine (dCyd) and several chemotherapeutically important nucleoside analogues. To investigate whether supplementation of docosahexaenoic acid, an n-3 fatty acid found mainly in fish oil, can modulate the activity of both enzymes, normal (Rat-2) and transformed (NW-16) rat fibroblasts were cultured in medium supplemented with or without DHA. DHA supplementation increased the phosphorylation efficiency (V(max)/K(m)) of dCK but decreased the deamination efficacy of dCDA in the transformed cells as compared with those in the normal fibroblasts. Enzyme activity of dCK was decreased by DHA in Rat-2 cells and increased in NW-16 cells. In contrast, dCDA activity was elevated in the normal fibroblasts in response to DHA. As a result, the activity ratio of dCK/dCDA (a potential indicator of chemosensitivity) was decreased in the normal fibroblasts but increased in the transformed cells by DHA. We have observed previously that the toxicity of nucleoside drugs (particularly arabinosylcytosine) was increased in tumor cells and decreased in normal cells in response to DHA and proposed a mechanism of changes in drug activation/inactivation. The present data support this hypothesis and suggest that DHA has the potential to selectively target chemotherapeutic drugs toward tumor cells while at the same time reducing host toxicity.     

The best of times, the worst of times The global challenge of antimicrobial resistance

The development of resistance to antimicrobial agents by many bacterial pathogens has compromised traditional therapeutic regimens, making treatment of infections more difficult and frequently more expensive. Three factors have contributed to the development and spread of resistance: mutations in common genes that extend their spectrum of resistance, transfer of resistance genes among diverse microorganisms and increases in selective pressures in and outside of the hospital environment that enhance the development of resistant organisms. Some new resistance mechanisms are difficult to detect in the laboratory. Thus, resistant microorganisms may go unnoticed until they are widely disseminated in a hospital. The challenge for pharmacists, microbiologists and physicians is not only to contain the spread of existing resistant organisms, but also to prevent the emergence of new resistant pathogens by encouraging the rational and prudent use of antimicrobial agents.     

腺苷脱氨酶、乳酸脱氢酶、癌胚抗原、肿瘤抗原19-9、肿瘤抗原125联合检测鉴别良恶性胸腔积液

目的探讨胸腔积液中腺苷脱氨酶（ADA）、乳酸脱氢酶（LDH）、癌胚抗原（cEA）、肿瘤抗原19—9（CA19—9）、肿瘤抗原125（CA125）联合检测在胸腔积液鉴别诊断中的意义。方法常规采集各80例结核性疾病组和恶性疾病组胸腔积液，测定胸腔积液ADA、LDH、CEA、CA125、CA19—9等五项指标，并进行对比分析。结果联合检测对结核性胸腔积液诊断的敏感度为92．5％、特异度为93．6％、准确度为92．7％；对恶性胸腔积液诊断的敏感度、特异性、准确度分别为92．3％、94．6％、93．5％。结论联合检测多项指标有效地避免了单一指标检测所致的误诊和漏诊，有助于胸腔积液的病因诊断。     

Inhibitory effect of digoxin on testosterone secretion through mechanisms involving decreases of cyclic AMP production and cytochrome P450scc activity in rat testicular interstitial cells

1. In vivo and in vitro experiments were performed to examine inhibitory effects of digoxin on testosterone secretion and to determine possible underlying mechanisms.
2. A single intravenous injection of digoxin (1 μg kg⁻¹) decreased the basal and human chorionic gonadotropin (hCG)-stimulated plasma testosterone concentrations in adult male rats.
3. Digoxin (10⁻⁷–10⁻⁴ M) decreased the basal and hCG-stimulated release of testosterone from rat testicular interstitial cells in vitro.
4. Digoxin (10⁻⁷–10⁻⁴ M) also diminished the basal and hCG-stimulated production of cyclic 3′ : 5′-adenosine monophosphate (AMP) and attenuated the stimulatory effects of forskolin and 8-Br-cyclic AMP on testosterone production by rat testicular interstitial cells.
5. Digoxin (10⁻⁴ M) inhibited cytochrome P450 side chain cleavage enzyme (cytochrome P450_scc) activity (conversion of 25-hydroxy cholesterol to pregnenolone) in the testicular interstitial cells but did not influence the activity of other steroidogenic enzymes.
6. These results suggest that digoxin inhibits the production of testosterone in rat testicular interstitial cells, at least in part, via attenuation of the activities of adenylyl cyclase and cytochrome P450_scc.

     

干扰素释放试验(γ-干扰素)、腺苷脱氨酶、结核分枝杆菌脱氧核苷酸在结核性胸膜炎诊断中的对比

目的 探讨干扰素释放试验(γ-干扰素)、腺苷脱氨酶(ADA)、结核分枝杆菌脱氧核苷酸(TB-DNA)在结核性胸膜炎诊断中的效果.方法 128例患者分为结核性胸腔积液(结核组)与非结核胸腔积液组(非结核组),并通过对2组患者的ADA、TB-DNA及IFN-γ三种因子进行检验,观察2组检查指标及其3组因子对结核性胸腔积液患者检测的灵敏度与特异性分析并评价其效能.结果 结核组与非结核组检测结果表明ADA及IFN-γ这两种种因子的检测含量及其检出阳性率差异有统计学意义(P<0.05),且2组间TB-DNA阳性检出率间差异有统计学意义(P<0.05).表明三种检测方法在对于结核性胸腔积液的诊断具有显著意义.单因子效能比较中,ADA的灵敏度要高于金标准,但特异性ADA检测相较于其他方法则相对较低,差异有统计学意义(P<0.05).TB-DNA灵敏度为41.28%其较之于涂片法的4.56%,差异有统计学意义(P<0.05).但相比与金标准培养法的灵敏度即在本试验中36.9%依然存在优势.IFN-γ指标测试结果为其灵敏度为76.49%、特异度为94.77%,暗示其检测指标具有很好的指导效能.在并联实验中,ADA或IFN-γ组合具有最高的灵敏度,与其他组比较,差异有统计学意义(P<0.05).而组合为TB-DNA或IFN-γ具有最高的特异性,与其他组比较,差异有统计学意义(P<0.05).其中约登指数最高的组合为TB-DNA或IFN-γ,串联结果特异度最高(99.98%).结论 三种检测方法分别单独使用局限性不能作为单独的诊断标准.使用其中2种大大增强对于该疾病的检出灵敏度与特异度.成为临床检测过程中阳性检出率低、活检过程复杂等相关问题的一大解决方案.     

Single-dose tolerance to the behavioral effects of dibutyryl cyclic AMP in mice

The behavioral effects of varying doses of intraperitoneally administered dibutyryl cyclic AMP, cyclic AMP, adenosine, 5-AMP, and butyric acid were studied in male ICR mice. Behavioral parameters 25 min following treatment included measurement of spontaneous locomotor activity (SLMA) and rotarod performance, the latter providing an indication of neuromuscular coordination. Dibutyryl cyclic AMP produced a dose-related inhibition of SLMA with the largest dose, 75 mg/kg, decreasing activity by 89%. Adenosine and 5-AMP produced maximal inhibition of approximately 50–80% of SLMA at doses ranging from 75–250 mg/kg, while cyclic AMP decreased SLMA by 58% at only the highest dose, 250 mg/kg. Butyric acid failed to produce alterations in SLMA at doses ranging from 25–250 mg/kg. No compound altered neuromuscular coordination. Single-dose tolerance to the inhibitory effect of dibutyryl cyclic AMP on SLMA developed within 3 h and lasted at least 7 days. Adenosine failed to produce tolerance while cyclic AMP and 5-AMP exhibited only a slightly reduced effect following a second injection at intervals of 4 and 24 h. These results suggest that exogenous administration of dibutyryl cyclic AMP and its metabolites exert centrally mediated behavioral effects with selective development of single-dose tolerance to the dibutyryl derivative.     

The effect of histamine on cyclic AMP levels in guinea-pig tracheal smooth muscle

Histamine (10(-5)--3 x 10(-4) M) increased the cylic AMP content of guinea-pig tracheal smooth muscle, the maximal effect being a 3-fold increase after 2-min incubation with 10(-4) histamine. Histamine-induced accumulation of cyclic AMP was not affected by propranolol or atropine, but was reduced by mepyramine. Aspirin and indomethacin abolished the cyclic AMP response to histamine and potentiated histamine-induced contractions of the smooth muscle. These results suggest that the elevation of cyclic AMP levels in response to histamine is mediated by prostaglandins, and represents an important negative feedback regulatory mechanism which modulates the contractile response of guinea-pig tracheal smooth muscle to histamine.     

5-Hydroxytryptamine 5-HT1D receptors mediating inhibition of cyclic AMP accumulation in Madin-Darby canine kidney (MDCK) cells

5-Hydroxytryptamine 5-HT_1B/5-HT_1D receptors are members of the same receptor subfamily, but display a different pharmacology (Hartig et al. (1992) Trends Pharmacol Set 13:152–159). Whereas several cell lines have been reported to contain 5-HT_1B receptors, none has been described, however, that endogenously expresses well-characterized 5-HT_1D receptors. The present study deals with the identification of 5-HT_1D receptors inhibiting cyclic AMP accumulation in Madin-Darby canine kidney (MDCK) cells. 5-HT (1 nM– 10 M) induced a concentration-dependent inhibition of the cyclic AMP accumulation stimulated by prostaglandin E₁ (1 M) in MDCK cells. The maximal effect of 5-HT averaged 50% inhibition and was abolished after a pre-treatment of the cells with pertussis toxin. Other agonists mimicked the effects of 5-HT, with the following rank order of potency (pEC₅₀ ± SEM, n 3): 5-carboxamidotryptamine (8.36 ± 0.48) > PAPP (p-aminophenylethyl-m-trifluoromethylphenyl piperazine, 7.89 ± 0.23) > 5-HT (7.35 ± 0.05) > sumatriptan (6.65 ± 0.27). PAPP behaved as a partial agonist. 8-OH-DPAT (8-hydroxy-2(di-n-propylamino)tetralin) was less potent, its maximal effect being not reached at 0.1 mM. Methiothepin, GR127935, (–)propranolol, rauwolscine and ketanserin were all devoid of intrinsic activity (up to 10 M or 0.1 mM). Methiothepin (10 nM, 0.1 M and 1 M) antagonized 5-HT effect (pA₂ 8.57 ± 0.44, Schild slope 1.17 ± 0.21, n = 3). GR127935 (1 nM, 10 nM and 0.1 M) shifted the curve of 5-HT to the right, but the antagonism was not fully surmountable (apparent pK_B value, 9.80 ± 0.16, n = 9). From the shifts obtained with rauwolscine (1 M) and (–)propranolol (10 M), respective pK_B values were estimated 6.68 ± 0.30 and 5.4 (n = 3 each). PAPP, when tested as an antagonist at 1 M, also shifted the curve of 5-HT to the right, with a pK_B of 8.27 ± 0.16 (n = 3). Finally, ketanserin (10 M) also antagonized the effects of 5-HT, the pK_B being 6.54 ± 0.16 (n = 9). The rank orders of agonist and antagonist potencies strongly suggest 5-HT receptors mediating inhibition of cyclic AMP accumulation in MDCK cells to be 5-HT_1D receptors. This is the first report of a cell line expressing endogenous, well-characterized, 5-HT_1D receptors. With regard to the 5-HT_1D receptor subtype involved, the relatively high potency of ketanserin would suggest it to be a 5-HT_1D subtype or a mixture of 5-HT_1D/5-HT_1D\ subtypes. However, caution must be exercised here, owing to the poor knowledge of canine 5-HT_1D receptor subtypes.     

The Effect of Lithium on Unstimulated and Glucagon-stimulated Urinary Cyclic AMP Excretion in Rat and Man

Abstract The purpose of this study was to determine whether lithium also inhibits hormone-stimulated adenylate cyclase in vivo. The effect of long-term lithium treatment on unstimulated and glucagon-stimulated cyclic AMP excretion was studied in the rat and in man. The influence of lithium on plasma glucagon degradation was also investigated. It was found that in the rat lithium doubled unstimulated and glucagon-stimulated urinary cyclic AMP excretion. In lithium treated rats plasma glucagon concentrations thirty minutes after intraperitoneal injection were twice that of the control rats. In man, lithium affected neither cyclic AMP excretion nor glucagon degradation. These results offer no support for the hypothesis that in vivo lithium in general inhibits hormone-stimulated adenylate cyclase. However, in the intact organism lithium may have additional pharmacological actions, and complex regulatory mechanisms which may modify the cyclic AMP metabolism. Therefore it may be premature to conclude that lithium per se does not have an inhibitory action on glucagon-sensitive adenylate cyclase in vivo.     

AMP579与腺苷对冠心病患者白介素-18表达及血小板聚集的影响

目的 研究AMP579(抗心律失常药)与腺苷对冠心病患者白介素-18(IL-18)表达和血小板聚集的影响.方法 在30例冠心病患者中,有15例为急性心梗、15例为不稳定型心绞痛;另将15例健康志愿者作为对照组.用双抗体夹心酶联免疫吸附法(ELISA)和透射比浊法,观察AMP579与腺苷对冠心病患者IL-18和血小板聚集的影响.结果 与对照组相比在低浓度时,AMP579和腺苷对IL-18表达有增强效应;高浓度时,有抑制效应.AMP579和腺苷对血小板聚集均具有显著抑制效应.结论 AMP579和腺苷浓度分别在10～100 μmol·L-1、30～300 μmol·L-1时对冠心病患者IL-18的表达有促进作用;而2药在高浓度(300、1 000 μmol·L-1)时对其有抑制作用.2药浓度在10 μmol·L-1时对血小板聚集均具有显著的抑制作用.     

Involvement of cyclic AMP in the direct inotropic action of amrinone

Summary Using the isolated guinea-pig papillary muscle and conventional methods for recording isometric force and transmembrane electrical activity we analysed the positive inotropic effect of the bipyridine derivative amrinone at a contraction frequency of 0.2 Hz. The drug produced a concentration-dependent (0.06–8.0 mmol/l), reversible increase in force of contraction associated with an abbreviation of relaxation time at low concentrations and an increase of this parameter at high concentrations. Part of the inotropic effect was manifested by the rested-state contraction. In muscles depolarized by 24 mmol/l [K]₀, amrinone increased the maximum rate of depolarization and overshoot of the slow responses. Carbachol reduced the inotropic effect of amrinone, and this antagonism was removed by the additional application of atropine. The inotropic effect of amrinone was not affected by propranolol or phentolamine and only slightly inhibited by cimetidine. Amrinone potentiated the positive inotropic effects of isoprenaline or histamine but interacted additively with dihydroouabain; the –log EC₅₀ of isoprenaline was increased by 0.803±0.077 and that of histamine by 1.14±0.054 logarithmic units in the presence of 0.2 mmol/l amrinone. Abbreviation of relaxation time, increase in force of the rested-state contraction, atropine-sensitive antagonism by carbachol, and the effects on the slow response are characteristic of the class of cardiotonic drugs thought to act by increasing the cellular concentration of cyclic AMP. Direct support for this hypothesis was provided by the demonstration that inotropically effective concentrations of amrinone produced an up to 3.5-fold increase in cyclic AMP content of guinea-pig papillary muscles. In addition, amrinone was found to inhibit phosphodiesterase in a crude enzyme preparation from guinea-pig ventricular strips. Lack of specific antagonism by propranolol or cimetidine and potentiation of the effects of isoprenaline or histamine are consistent with an inhibitory effect on cyclic nucleotide phosphodiesterase. At high concentrations, amrinone was shown to exert an additional theophylline-like effect on the contour of the isometric contraction that cannot be attributed to cyclic AMP accumulation.     

Effects of lithium in vitro on noradrenaline-induced cyclic AMP accumulation in rat cortical slices after reserpine-induced supersensitivity

Lithium in vitro at concentrations of 1-2 mM and above inhibited cyclic AMP accumulation due to noradrenaline in cerebral cortical slices prepared from both control rats and rats rendered supersensitive for the noradrenaline response by intraperitoneal injection of reserpine. There was no difference in the concentration-dependence of lithium inhibition between control and reserpine-treated rats.     

Ethanol-induced changes in gastric mucosal content of cyclic AMP and ATP in the rat.

The stomach of urethane-anaesthetised rats was perfused with 10% (v/v) ethanol. At 40 min, the secretion of acid was strongly inhibited and the contents of cyclic AMP and ATP were lowered in the superficial mucosa, but not in whole gastric mucosa. After discontinuation of the ethanol perfusion, the rate of gastric acid output as well as the cyclic AMP and ATP levels recovered. Most of the acid-secreting parietal cells were found in the superficial mucosa where the changes of cyclic AMP and ATP took place. The results suggest that lowering of the mucosal contents of cyclic AMP and ATP may be involved in the ethanol-induced inhibition of the gastric acid output.