羧甲基壳聚糖对肺泡液体清除率的作用研究

目的探讨羧甲基壳聚糖与肺泡液体清除率(Alveolar fluid clearance,AFC)之间的关系,阐明羧甲基壳聚糖是否参与了肺上皮液体转运。方法应用酶标仪测定小牛血清白蛋白浓度的方法测定小鼠在体AFC。结果羧甲基壳聚糖气管内给药对AFC无明显抑制作用。结论羧甲基壳聚糖可能不影响肺泡上皮钠主动转运机能,抑制肺水肿液的吸收。     

氯胺酮对小鼠肺泡上皮液体清除作用的研究

<正>肺泡液体清除率(alveolar fluid clearance,AFC)对肺脏生理和病理状态下的液体平衡,如肺水肿、急性肺损伤和成人呼吸窘迫症,均起重要的调控作用。肺泡上皮细胞顶侧膜的上皮钠通道(epithelial sodium channel,ENaC)是影响AFC的     

非心源性肺水肿的临床X线诊断分析

目的通过对在我院确诊的非心源性肺水肿患例的统计,确定在临床上用X线诊断分析的方法诊断该类疾病的有效性。方法通过总结2010年1月至2012年3月期间进入我院治疗的非心源性肺水肿患例的临床资料,根据各个患例自身疾病的不同特点,分析了临床X线的影像特征,最后用统计学方法统计了该类患例依次用传统病因病史诊断和临床X线诊断差异性。结果急性呼吸窘迫综合征类肺水肿临床X线影像表现为弥漫性肺泡实变影,病情发展后,临床X线影像为透亮度明显降低;神经性肺水肿临床X线影像表现为肺部雾状特征,统计学结果表明单纯通过病因病史诊断与临床X线诊断的误诊率具有差异性(P<0.05)。结论临床X线诊断结合病因病史诊断的诊断方法能够对非心源性肺水肿患例进行确诊。     

高分辨率CT在心源性肺水肿中诊断价值

<正>心源性肺水肿是一种临床常见的疾病,见于各种原因引起左心功能不全所致,根据水肿聚集的部位可分为间质性肺水肿和肺泡性肺水肿~([1]);另外,根据临床表现分为急性心源性肺水肿和慢性心源性肺水肿~([2]),急性心源性肺水肿是以肺泡性肺水肿表现为主,临床症状较重,发病较急,结合病史及相关检查较易诊断;而慢性心源性肺水肿则主要表现为间质性肺水肿,症状较轻,病程进展缓慢,在临床中与其他间质性肺疾病鉴别具有一定难度~([3])。为了提供更多心源性肺水肿的诊断依据,笔者对心源性肺水肿患者高分辨率CT进行了如下回顾性分析。     

心源性肺水肿的X线诊断价值

目的探讨心源性肺水肿X线表现特点,为临床提供诊断和治疗依据。方法回顾性分析53例心源性肺水肿的临床影像资料。结果胸腔积液45例,肺淤血9例,间质性肺水肿32例,肺泡性肺水肿12例,53例均有心影增大。结论心源性肺水肿肺部X线表现具有一定的特征性。     

非心源性肺水肿的X线影像表现

目的探讨非心源性肺水肿(NCPE)的胸部X线影像表现。方法回顾性分析35例NCPE患者胸片。其中,溺水后肺水肿21例(60%),神经源性肺水肿9例(26%),有害气体中毒性肺水肿2例(6%),有机磷农药中毒肺水肿2例(6%),百草枯中毒肺水肿1例(3%)。结果早期表现为两肺纹理增多、增粗、模糊或伴弥漫小点状模糊影9例(26%);中晚期表现为多发斑片状阴影8例(23%)或融合成大片状阴影10例(29%),云雾状模糊阴影5例(14%)及多发棉球状阴影3例(8.5%)。所有病例均无心影改变。结论各类NCPE的病理机制不尽相同,但最终均导致肺毛细血管渗透性改变,肺血容量过高,血浆渗透压过低等,液体渗入肺泡及肺泡间隙,形成弥漫性肺水肿。     

重症急性心源性肺水肿序贯通气治疗护理中应注意的几个问题

机械通气是抢救各种原因所导致的急性呼吸衰竭(ARF)的有效手段,从病理生理角度认识呼吸衰竭(呼衰)的病因为通气障碍、非心源性肺水肿及心源性肺水肿。典型的代表疾病为慢性阻塞性肺部疾病(COPD)、急性呼吸窘迫综合征(ARDS)和急性心源性肺水肿(ACPE)。近年来国内外研究的重点是C     

高原肺水肿的治疗研究进展

<正>高原肺水肿(high altitude pulmonary edema,HAPE)是一种非心源性肺水肿,是由于快速进入高原(指海拔在3000m以上)或从高原进入更高海拔地区机体对高原低压低氧环境不适应,而引起肺动脉压突然升高,肺循环血量增加,肺毛细血管内皮和肺泡上皮细胞受损、通透性增加,体液潴留及转移,导致液体自肺毛细血管漏至肺间质或     

纤溶酶对小鼠肺泡上皮液体清除作用的研究

目的探讨纤溶酶对在体小鼠肺泡液体清除率(AFC)的作用。方法应用考马斯亮蓝法测定小牛血清白蛋白浓度的方法测定小鼠在体AFC。结果特异性上皮细胞钠通道阻断剂阿米洛利组能明显降低AFC,气管内注入60μg/mL纤溶酶后,AFC明显增加(38.2±2.1)%,与对照组相比P<0.05,n=6)。纤溶酶+阿米洛利组对AFC的影响与对照组相比差异无统计学意义(P>0.05,n=5),与单独使用纤溶酶比较差异有统计学意义(P<0.05)。结论纤溶酶能明显增加肺泡上皮液体的清除,可能通过增强阿米洛利敏感性钠通道活性而影响AFC。     

慢性阻塞性肺疾病患者肺泡液体清除作用机制研究

目的本研究旨在探讨慢性阻塞性肺疾病(COPD)患者离体肺段肺泡液体清除率(AFC)的改变及其与环磷酸鸟苷(cGMP)依赖性蛋白激酶2(PKG2)的关系。方法应用临床外科手术肺切除患者的肺段标本,将药物通过插管注入远端肺组织。应用考马斯亮兰法测定肺泡液体内小牛血清白蛋白浓度的方法测定人离体肺段AFC。应用相关酶联免疫试剂盒检测PKG2。结果 COPD患者肺组织AFC增加,PKG2明显高于对照组。结论 COPD患者气道黏液分泌增多肺脏液体清除作用增强,其机制可能与上皮钠通道功能增强有关。     

Effects of asphalt fume condensate exposure on acute pulmonary responses

OBJECTIVE: The present study was carried out to characterize the effects of in vitro exposure to paving asphalt fume condensate (AFC) on alveolar macrophage (AM) functions and to monitor acute pulmonary responses to in vivo AFC exposure in rats. METHODS: For in vitro studies, rat primary AM cultures were incubated with various concentrations of AFC for 24 h at 37 degrees C. AM-conditioned medium was collected and assayed for lactate dehydrogenase (LDH) as a marker of cytotoxicity. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) production were assayed in AM-conditioned medium to monitor AM function. The effect of AFC on chemiluminescence (CL) generated by resting AM or AM in response to zymosan or PMA stimulation was also determined as a marker of AM activity. For in vivo studies, rats received either (1) a single intratracheal (IT) instillation of saline, or 0.1 mg or 0.5 mg AFC and were killed 1 or 3 days later; or (2) IT instillation of saline, or 0.1, 0.5, or 2 mg AFC for three consecutive days and were killed the following day. Differential counts of cells harvested by bronchoalveolar lavage were measured to monitor inflammation. Acellular LDH and protein content in the first lavage fluid were measured to monitor damage. CL generation, TNF-alpha and IL-1 production by AM were assayed to monitor AM function. RESULTS: In vitro AFC exposure at <200 microg/ml did not induce cytotoxicity, oxidant generation, or IL-1 production by AM, but it did cause a small but significant increase in TNF-alpha release from AM. In vitro exposure of AM to AFC resulted in a significant decline of CL in response to zymosan or PMA stimulation. The in vivo studies showed that AFC exposure did not induce significant neutrophil infiltration or alter LDH or protein content in acellular lavage samples. Macrophages obtained from AFC-exposed rats did not show significant differences in oxidant production or cytokine secretion at rest or in response to LPS in comparison with control macrophages. CONCLUSIONS: These results suggest that: (1) in vitro AFC exposure did not adversely affect cell viability or induce the release of high levels of inflammatory cytokines or oxidants; and (2) exposure of rats to AFC did not cause acute pulmonary inflammation or injury, and did not significantly alter AM functions.     

Separation and identification of flavonoid constituent in Humulus Seandens and their effects on alveolar fluid clearance in mice北大核心CSCD

Aims To extract, separate and identify the flavonoid constituents in Humulus Seandens and to explore the relationship of monomers and alveolar fluid clearance (AFC) in mice in vivo. Methods Humulus seandens were extracted with alcohol and then isolated by the technology of Column and the structures were identified by spectrometry. In vivo AFC was measured using bovine serum albumin protein assays affected by luteolin-7-O-β-D-glucoside (LGL) and cosmsiin (AGL). Results The main constituents of flavanones in Humulus seandens were LGL and AGL. Both of them could improve the AFC. Conclusion The AFCs of LGL and AGL, compared to the blank control group, increased which explains the effect of flavonoid constituents on removing edema and promoting water absorption.     

Dose-dependent effects of verapamil and nifedipine on in vivo platelet function in normal volunteers

The effects of 1 week of treatment with low and moderate doses of verapamil or nifedipine upon platelet function has been studied in 12 healthy volunteers. The ex vivo platelet aggregation threshold for ADP or adrenaline was not altered by verapamil or nifedipine. The plasma concentrations of beta-thromboglobulin and platelet factor 4 were significantly reduced by low but not by moderate doses of verapamil and nifedipine. Low doses of verapamil and nifedipine inhibit in vivo platelet activity in healthy volunteers.     

咪达唑仑对小鼠肺泡上皮液体清除作用的研究

目的探讨咪达唑仑与在体小鼠肺泡液体清除率(AFC)之间的关系,以及β2肾上腺素受体激动剂特布他林对其作用的影响。方法应用酶标仪测定小牛血清白蛋白浓度的方法测定小鼠在体AFC。结果气管内注入0.1mmol/L咪达唑仑后,能显著降低小鼠AFC。与1mmol/L阿米洛利(特异性钠通道阻断剂)合用后抑制效应未见进一步增强,表明咪达唑仑能够抑制与上皮钠通道有关的阿米洛利敏感性AFC。β2肾上腺素受体激动剂特布他林能明显增加小鼠AFC,与咪达唑仑合用后,特布他林几乎完全逆转咪达唑仑对AFC的抑制作用。结论临床上对合并肺脏损害的患者应用咪达唑仑时应考虑其可能对肺脏液体清除作用的影响,必要时可以考虑应用β2肾上腺素受体激动剂特布他林进行治疗。     

Antibronchoconstrictor activity of the intracellular calcium antagonist HA 1004 in guinea pigs

HA 1004 is a calcium antagonist vasodilator that inhibits contraction in vascular smooth muscle and lowers arterial blood pressure. The effects of HA 1004 on guinea pig airway smooth muscle contraction were compared to the effects of the calcium antagonists, verapamil and nifedipine and the bronchodilator, albuterol. In vitro, HA 1004, verapamil, nifedipine and albuterol inhibited Ca2+-induced contractions of the depolarized guinea pig trachea. HA 1004 and albuterol also relaxed the basal tracheal tone, whereas verapamil and nifedipine were inactive. The bronchorelaxant activity of HA 1004 was not blocked by propranolol. In vivo, intravenous administration of HA 1004, verapamil, nifedipine and albuterol effectively blocked bronchoconstriction induced by intravenous histamine and methacholine. HA 1004 also reversed a histamine-induced bronchospasm, as did albuterol, verapamil and nifedipine. Intratracheal administration of HA 1004 and albuterol inhibited histamine-induced bronchoconstriction without effecting blood pressure, whereas intratracheal administration of verapamil and nifedipine caused a significant reduction of blood pressure at their pulmonary active doses. These results show that HA 1004 has the ability to relax airway smooth muscle, inhibit contractile responses in the guinea pig airways, and there is separation of its cardiovascular and pulmonary effects when HA 1004 is administered directly to the lungs. The results are discussed in terms of the regulatory enzymes and sources of calcium that are involved in airway smooth muscle contraction.     

Nifedipine toxicity is exacerbated by acetyl l-carnitine but alleviated by low-dose ketamine in zebrafish in vivo

Calcium channel blocker (CCB) poisoning is a common and sometimes life-threatening emergency. Our previous studies have shown that acetyl l -carnitine (ALCAR) prevents cardiotoxicity and developmental toxicity induced by verapamil, a CCB used to treat patients with hypertension. Here, we tested whether toxicities of nifedipine, a dihydropyridine CCB used to treat hypertension, can also be mitigated by co-treatment with ALCAR. In the zebrafish embryos at three different developmental stages, nifedipine induced developmental toxicity with pericardial sac edema in a dose-dependent manner, which were surprisingly exacerbated with ALCAR co-treatment. Even with low-dose nifedipine (5 μm ), when the pericardial sac looked normal, ALCAR co-treatment showed pericardial sac edema. We hypothesized that toxicity by nifedipine, a vasodilator, may be prevented by ketamine, a known vasoconstrictor. Nifedipine toxicity in the embryos was effectively prevented by co-treatment with low (subanesthetic) doses (25-100 μm added to the water) of ketamine, although a high dose of ketamine (2 mm added to the water) partially prevented the toxicity.As expected of a CCB, nifedipine either in the presence or absence of ketamine-reduced metabolic reactive oxygen species (ROS), a downstream product of calcium signaling, in the rapidly developing digestive system. However, nifedipine induced ROS in the trunk region that showed significantly stunted growth indicating that the tissues under stress potentially produced pathologic ROS. To the best of our knowledge, these studies for the first time show that nifedipine and the dietary supplement ALCAR together induce adverse effects while providing evidence on the therapeutic efficacy of subanesthetic doses of ketamine against nifedipine toxicity in vivo.     

Quercetin,an in vitro inhibitor of CYP3A,does not contribute to the interaction between nifedipine and grapefruit juice

Quercetin, a flavonoid present in various fruits, is a potent in vitro inhibitor of CYP3A. Its role in the reported interaction between grapefruit juice and nifedipine has been determined in vivo in humans. Eight healthy volunteers were given in random order 10 mg nifedipine orally, either alone or with 200 ml double strength grapefruit juice, or with 400 mg quercetin. The area under the plasma concentration-time curve (AUC) for nifedipine with grapefruit juice (mean 320 ng ml(-1) h) was increased significantly (P < 0.01) compared with the AUC when nifedipine was given alone (mean 218 ng ml(-1) h). The time to peak plasma concentration for nifedipine with grapefruit juice (1.5 h) was also increased (P < 0.05) compared with control (0.5 h) suggesting delayed absorption. Although quercetin delayed the time to peak nifedipine concentration (1.3 h) it did not alter the AUC of either the parent drug (mean 209 ng ml(-1) h) or its first-pass metabolite. The results suggest that quercetin does not contribute to the effects of grapefruit juice (which contains <10 mg of quercetin 200 ml(-1)) on the metabolism of nifedipine. Oral doses of quercetin, similar to those possible from the ingestion of other fruits such as strawberries, do not produce in vivo inhibition of CYP3A mediated metabolism of nifedipine.     

Alteration of pulmonary cytochrome p-450 system: effects of asphalt fume condensate exposure

Exposure to asphalt fumes is a health concern due to the presence of polycyclic aromatic compounds (PACs) in asphalt. Bioactivation of many PACs requires metabolism by the cytochrome P-450 (P-450) system. The objective of this study was to evaluate the effects of exposure of rats to asphalt fume condensate (AFC), collected at the top of a paving asphalt storage tank, on the pulmonary microsomal P-450 system and to determine the genotoxic effects of such exposure. Male Sprague-Dawley rats were intratracheally instilled with saline or with 0.45, 2.22, or 8.88 mg/kg AFC for 3 consecutive days and sacrificed the following day. Lung microsomes were isolated by differential centrifugation of lung homogenates. Microsomal protein level, NADPH cytochrome c reductase activity, and the activities and protein levels of cytochrome P-450 isozymes CYP1A1 and CYP2B1 were monitored to assess the effects of AFC exposure on pulmonary P-450. The activities of CYP2B1 and CYP1A1 were determined by monitoring xenobiotic metabolism of 7-pentoxyresorufin and 7-ethoxyresorufin, respectively. CYP2B1 and CYP1A1 levels were determined by immunochemical analysis. Micronucleus (MN) formation in bone-marrow polychromatic erythrocytes (PCEs) was determined to assess the genotoxic effects of AFC exposure. The results showed that exposure of rats to AFC did not significantly affect total cytochrome P-450 content or cytochrome c reductase activity in the lung. CYP2B1 levels and enzyme activity were not significantly affected by AFC exposure. In contrast, CYP1A1 levels and activity were significantly increased in microsomes isolated from AFC-exposed lungs. Increased MN formation was observed only in high-dose AFC-exposed bone marrow PCEs. These results demonstrate that AFC exposure induced CYP1A1 activity and increased the enzyme levels of CYP1A1 in lung microsomes, suggesting that AFC exposure may alter metabolism of PACs by the cytochrome P-450 system in the lung. Alteration of cytochrome P-450 metabolism of PACs may contribute to the AFC-induced genotoxic effects demonstrated as MN formation.     

Suppression of the antibody response by phorbol esters in the mouse is due to an effect on the nylon wool adherent cell population

Phorbol esters, in particular 12-O-tetradecanoyl-phorbol-13-acetate (TPA), have been shown to have profound effects on most biological systems including tumor promotion. Presented here are studies on the acute toxic effects of TPA, and the effects of phorbol esters on the in vivo and in vitro, T cell-dependent, antigen-specific antibody response in the mouse. The LD50 of a single i.v. dose of TPA in the mouse was 309 micrograms/kg. Acute toxic effects included lethargy, hypothermia and enlarged, hemorrhagic spleens at the higher doses. TPA was shown to be a potent inhibitor of the in vivo primary antibody response as measured by the IgM antibody-forming cell (AFC) response to sheep red blood cells (sRBC). The ED50 of a cumulative i.v. dose was 145 micrograms/kg administered the day before and the day of immunization (72.5 micrograms/kg/day). A cumulative dose of 500 micrograms/kg (250 micrograms/kg/day) resulted in a 100% suppression of the response. This in vivo exposure to TPA did not alter B cell/T cell ratio in the spleen. Phorbol ester analogs inactive in other biological systems were also inactive in the in vivo AFC response. The in vitro AFC assay was used to determine what cell type was being affected by TPA. Separation of the adherent spleen cells into B and T cell populations was done using nylon wool columns and anti-theta plus complement treatment. Experiments with these cell populations indicated that TPA produced suppression of the response due to an effect on the nylon wool adherent cell population.