Morphological Aspects of Necrosis as a Guideline for Treatment of Necrotizing Pancreatitis (A Brief Report About 50 Patients)

In a retrospective study, 50 patients withobvious necrotizing pancreatitis (NP) were allocated infour groups according to the morphological aspects ofthe necrosis. Appearance of ascite (N1), extrapancreatic spread of necrosis towards neighboring organs(N2), a large amount of necrosis (N3), and infectednecrosis (N4), appears to be an easy and usefulguideline for the management of NP patients. Organfailures (72%) and mortality rate (36%) are higher whenthe process is infected. In the other groups, organicdysfunctions were frequent, but all the patients exceptone survived. The majority (80%) of patients were operated on. Only 20% of patients hadsuccessful nonsurgical treatment and they were in N3group. This percentage may increase through amorphological approach to treating necrosis, with theuse of endoscopic treatment for the disruption ofpancreatic duct, and better accuracy in the managementof patients with noninfected necrosis, whenever organfailures are present.     

Pseudocysts in Acute Nonalcoholic Pancreatitis (Incidence and Natural History)

Epidemiological studies on pancreaticpseudocysts are retrospective analyses on alcoholicpatients. The aims of this study were to investigate theincidence, natural history, and predictors of theappearance and disappearance of pancreatic fluidcollections and pseudocysts after nonalcoholic acutepancreatitis. We carried out a prospective cohort studyin a series of 926 patients with acute pancreatitis.Pancreatic fluid collections or pseudocysts were treatedonly after complications. We studied pancreatic fluidcollections from 83 patients (8.9%): 48 of whomdeveloped pseudocysts (5.1%). Both were less frequent after biliary pancreatitis (P < 0.0001). Inthe first 60 days of follow-up, patients with fluidcollections or pseudocysts showed more complicationsthan spontaneous disappearance; two of them died. After the 60th day, spontaneous disappearancewas more frequent, and at one year the cumulativeincidence of complications and spontaneous disappearancewas 36% and 56%, respectively. A total of 33 patients with fluid collection needed interventionaltreatment (surgery or percutaneous or endoscopicdrainage). Pseudocysts that were small (<5 cm) ordeveloped in the tail had a higher incidence ofspontaneous disappearance: 22/24 (91.7%) and 11/12 (91.7%),respectively. In conclusion, fluid collections andpseudocysts after nonalcoholic pancreatitis have a lowincidence of complications and mortality with a high rate of spontaneous disappearance. Wesuggest treating them only aftercomplications.     

Clinical Relevance of Acute Pancreatitis in Allogeneic Hemopoietic Stem Cell (Bone Marrow or Peripheral Blood) Transplants

This study investigated the clinical relevanceof acute pancreatitis in allogeneic hemopoietic stemcell (bone marrow or peripheral blood) transplants(BMT). We studied 26 patients undergoing BMT. Thepreparative regimen was busulfan and cyclophosphamide in 17patients and total body irradiation and cyclophosphamidein 9 patients. Graft-versus-host disease (GVHD)prophylaxis consisted of cyclosporin A and short-term methotrexate in all 26 patients. The pancreaswas studied using amylase and lipase serum levels,abdominal contrast-enhanced tomography, and/orultrasound. Clinical and laboratory signs of acutepancreatitis were found in two patients with acutehepatointestinal GVHD, and in one patient with acutehepatic GVHD and cytomegalovirus infection. This patientdied of multiorgan failure, with interstitial acutepancreatitis at autopsy; the other two patients recoveredwith general supportive care and GVHD therapy. Wesuggest that in the patients with complications afterBMT, particularly acute hepatic/hepatointestinal GVHD, and cytomegalovirus infection, the possibilityof acute pancreatitis should be considered.     

Novel Carboxamide Derivative (IS-741) Attenuates Lung Injury in Rats with Cerulein-Induced Pancreatitis Complicated by Endotoxemia

The therapeutic effects of an intravenouslyinjected carboxamide derivative (IS-741) on lung injurywere studied in rats with cerulein-induced pancreatitiscomplicated by endotoxemia. Pancreatitis was induced by four intramuscular injections of cerulein(50 g/kg at 1-hr intervals). Pancreatitis rats wereinjected intraperitoneally with 10 mg/kg oflipopolysaccharide (LPS) 6 hr following the firstcerulein injection as a challenge of endotoxemia. Ratswere divided into four groups: group I, pancreatitiswith LPS; group II, pancreatitis with LPS treated witha continuous intravenous injection of IS-741 at 0.03 mg/kg/hr); group III, pancreatitis withLPS treated with a continuous intravenous injection ofIS-741 at 0.3 mg/kg/hr); and group IV, pancreatitis withLPS treated with a continuous intravenous injection of IS-741 at 3 mg/kg/hr). IS-741 wasadministered 30 min before the endotoxemia challenge.Intense mononuclear cell infiltration and lunghemorrhage occurred in untreated pancreatitis rats withLPS (group I), but hemorrhage was not seen in group IVrats receiving a continuous injection of IS-741 shortlybefore the induction of endotoxemia. The IS-741- treatedrats (groups II, III, and IV) had lower serum concentrations of cytokine-induced neutrophilchemoattractant (CINC), as well as fewer pulmonaryinfiltrates immunoreactive for CINC or Mac-1(CD11b/CD18). The number of neutrophils infiltrating thelung in groups II, III, and IV was significantlylower than that of group I. Conversely, CINC productionby bronchoalveolar macrophages in vitro were stimulatedby LPS but were reduced by the presence of IS-741. The carboxamide derivative IS-741 effectivelyprevented pancreatitisassociated lung injury followingthe challenge of endotoxemia.     

Differential Induction of HSP60 and HSP72 by Different Stress Situations in Rats (Correlation with Cerulein-Induced Pancreatitis)

We previously reported that water-immersionstress specifically induced the synthesis of a 60-kDaheat-shock protein (HSP60, chaperonin homolog) inpancreatic cells and preinduction of HSP60 completely prevented development of cerulein-inducedpancreatitis in the rat in an HSP60 quantitativelydependent manner. In order to study the cytoprotectivefunction of a 72-kDa heat-shock protein (HSP72,stress-inducible hsp70), the effect of specific preinduction ofHSP72 by hyperthermia on cerulein-induced pancreatitiswas investigated and compared with the effect ofpreinduction of HSP60 in this study. Expression of HSP60 and HSP72 in the pancreas wasinvestigated by immunoblot before and after waterimmersion or hyperthermia. Following pretreatment withwater-immersion stress or hyperthermia, the rats wereinjected with cerulein (40 g/kg, intraperitoneally).The pancreas wet weight and serum amylase concentrationwere measured before and after cerulein injection.Hyperthermia (42.5°C, 20 min) specifically induced HSP72 in the pancreas. The synthesis of HSP60was specifically induced by water-immersion stress inthe pancreas. Cerulein-induced pancreatitis was clearlyprevented by specific preinduction of HSP60 by water-immersion stress. However, preinductionof HSP72 by hyperthermia had no preventive effect oncerulein-induced pancreatitis. Our findings suggest thatHSP60 and HSP72 have distinct functions in the pancreas, and their induction mechanisms arealso different in vivo. These results could be importantfor understanding the mechanism of adaptivecytoprotection in the pancreas mediated byheat-shock proteins.     

Trypsinogen activation peptides (TAP) concentrations in the peritoneal fluid of patients with acute pancreatitis and their relation to the presence of histologically confirmed pancreatic necrosis.

This study measured the volume and colour, as well as concentrations of trypsinogen activation peptides (TAP) in the peritoneal fluid of 22 patients with acute pancreatitis and related these findings to the presence of pancreatic necrosis. Nine patients had a severe attack with histologically confirmed pancreatic necrosis, seven a severe attack without confirmed necrosis, and six a mild attack, also without confirmed necrosis. A free fluid volume > 20 ml or free fluid colour > grade 5 on the Leeds chart, or both detected histologically confirmed pancreatic necrosis with a sensitivity of 100% and specificity of 31%. A total peritoneal fluid TAP concentration of > or = nmol detected histologically confirmed pancreatic necrosis with a sensitivity of 89% and specificity of 85%, figures comparable with contrast enhanced computed tomography. These findings suggest that the measurement of peritoneal fluid TAP concentrations can detect effectively histologically confirmed pancreatic necrosis and that such measurements may prove useful in the selection of patients for surgery.     

A Study on the Activation Peptide Released from Procarboxypeptidase B (CAPAP) and Anionic Trypsinogen in Patients with Acute Abdominal Disorders of Non-Pancreatic Origin

Background: The activation peptide released from procarboxypeptidase B, CAPAP, is a marker of the activation of pancreatic enzymes in acute pancreatitis while anionic trypsinogen (AT) levels in urine relate to leakage of unac- tivated proenzymes. Data on these markers in patients suffering from severe acute abdominal disorders of nonpancreatic origin are lacking. Purpose: To examine levels of CAPAP and AT in serum and urine from patients with severe acute abdominal disorders of non-pancreatic origin in order to better define the diagnostic specificity of these two markers in severe acute pancreatitis in relation to other acute intra-abdominal disorders.Subjects and Methods: The study included 54 patients with severe acute abdominal disorders of non-pancreatic origin with an APACHE II score > 3. Immunoreactive CAPAP (ir CAPAP) and immunoreactive AT (ir AT) were measured in serum and urine using specific immunoassays.Results: In urine, ir CAPAP levels were mildly increased (>2 nmol/l) in 13% of the patients with severe acute abdominal diseases of non-pancreatic origin, but on no occasion did the increase approach the cutoff levels described for severe acute pancreatitis (> 100 nmol/l). However, ir AT levels in serum and urine were increased (>50 ^g/l) in 54% of the cases.Conclusion: Contrary to what is found for ir AT, patients with acute abdominal pain of non-pancreatic origin rarely have markedly increased levels of ir CAPAP in serum and urine.     

Pathogenic Role of Endothelial Nitric Oxide Synthase (eNOS/NOS-III) in Cerulein-Induced Rat Acute Pancreatitis

Nitric oxide (NO) is a potent pancreatic vasodilator, yet the pathogenic role of NO in acute pancreatitis remains controversial. NO is generated from L-arginine by NO synthase (NOS), classified into three isozymes: neuronal (nNOS), inducible (iNOS), and endothelial NOS (eNOS). The purpose of the present study was to investigate the role of NO/NOS isozymes in the pathogenesis of cerulein-induced acute pancreatitis in rats. Acute pancreatitis was induced in male Wistar rats by two subcutaneous injections of cerulein (20 μg/kg). N ^G-Nitro-L-arginine methyl ester (L-NAME: a nonselective NOS inhibitor) or aminoguanidine (a relatively selective iNOS inhibitor) was given orally, while tetrahydrobiopterin (BH₄), a critical cofactor for NOS, was administered intraperitoneally 30 min before the first cerulein injection. Cerulein given repeatedly twice produced acute pancreatitis, with concomitant increases in the serum amylase level, pancreas weight, myeloperoxidase activity, lipid peroxidation and microvascular permeability. Prior administration of L-NAME, but not aminoguanidine, significantly prevented these changes, in a dose-dependent manner, and this effect was antagonized by the coadministration of L-arginine, a precursor of NO. The expression of dimetric eNOS in the pancreas was markedly suppressed by cerulein injections, together with a decrease in NO production, but the response was partially but significantly reversed by the prior administration of BH₄. The increases in the serum amylase level and pancreas weight, as well as the lipid peroxidation induced by cerulein, were significantly attenuated by the administration of BH₄. L-NAME had no effect on pancreatic secretion induced by cerulein. These results suggest that the uncoupled eNOS, probably caused by the decrease in endogenous BH₄ availability, plays a deleterious role in the pathogenesis of cerulein-induced acute pancreatitis.     

卡托普利晚期预处理对缺氧复氧心肌细胞游离钙的影响

目的观察卡托普利晚期预处理对缺氧复氧心肌细胞游离钙的影响,评价其延迟心肌的保护作用。方法建立培养乳鼠心肌细胞缺氧复氧损伤模型。设正常对照组、缺氧复氧组、缺氧预适应组、卡托普利预处理组、蛋白激酶C阻断剂+卡托普利组、一氧化氮合酶阻断剂+卡托普利组和核因子κB阻断剂+卡托普利组。利用分光光度计测定丙二醛和超氧化物岐化酶含量;全自动生物化学分析仪测定乳酸脱氢酶含量。Flou3AM负载染色和流式细胞分析技术测定细胞内钙离子浓度。结果卡托普利预处理和缺氧预处理均可减轻缺氧再灌注时心肌细胞内钙离子浓度增加(594±5nmolL、507±32nmolL比789±9nmolL,P<0.01),抑制乳酸脱氢酶和丙二醛的增加和超氧化物岐化酶含量的降低;但与对照组(414±37nmolL)比较钙内流仍有轻度增加(P<0.05);预先分别加入蛋白激酶C阻断剂、一氧化氮合酶阻断剂、核因子κB阻断剂与卡托普利共同孵育细胞,行缺氧复氧损伤所测得细胞内钙离子浓度分别为676±32nmolL、700±37nmolL和689±11nmolL,与卡托普利预处理组比较有所增加(P<0.05);但与缺氧复氧组比较仍有降低(P<0.05)。结论以上提示,卡托普利预处理可抑制缺氧复氧时的钙超载及其脂质过氧化损伤。其机制可能是通过轻度增加钙内流、启动心肌延迟保护作用;其过程可能涉及蛋白激酶C、一氧化氮合酶和核因子κB信号转导通路中的多个环节。     

Similar Time-Course of Interleukin-1 Beta Production and Extracellular-Signal-Regulated Kinase (ERK) Activation in Permanent Focal Brain Ischemic Injury

The present study investigated the activation of extracellular-signal-regulated kinase (ERK) and the potential role of interleukin-1 beta (IL-1) in the brain's response to focal brain ischemia in the permanent middle cerebral artery occlusion (pMCAO) model. Phosphorylated ERK p44 and p42 were increased time-dependently and significantly 18- and 28-fold, respectively, at 24-h post-pMCAO. Similarly, IL-1 protein levels were significantly increased with the peak at 24 h in the lesioned core of the ischemic hemisphere compared to the contralateral side. Previous studies using various stimuli have shown ERK-dependent IL-1 induction. The results from our study suggest that this relation may also exist in vivo in ischemic brain tissue. Based on the progressive nature of IL-1 induction, we hypothetized that inhibition of interleukin-converting enzyme (ICE) could provide an extended time-window for neuroprotection. Therefore, we applied N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD·fmk), an ICE blocker 3 or 6 h after pMCAO. Reductions of infarct volume, however, were not observed. Taken together with previous results, where we showed protective activity of zVAD·fmk when given immediately after pMCAO, we conclude that the time window for zVAD·fmk is less than 3 h.     

K_(ATP)通道开放剂对模拟缺血-再灌注时培养乳鼠窦房结细胞的保护作用及机制探讨

为探讨三磷酸腺苷敏感性钾通道 (简称KATP通道 )开放剂对模拟缺血 再灌注时培养的乳鼠窦房结细胞的保护作用及其可能机制。分离乳鼠窦房结细胞 ,纯化培养 2天后进行实验。随机分为对照组、模拟缺血 再灌注组 (I/R组 )、KATP通道开放剂Pinacidil干预组 (P +I/R组 )及KATP通道阻断剂干预组 (5 HD +P +I/R组与 5 HD +I/R组 )。以流式细胞术检测各组窦房结细胞存活率 ;用激光共聚焦显微镜测定各组窦房结细胞内钙。结果 :①I/R组窦房结细胞存活率 (51 .79%± 6 .2 8% )较对照组 (95 .0 8%± 1 0 .48% )明显降低 (P <0 .0 0 1 ) ;P +I/R组 (63 .77%± 5 .35 % )则较I/R组显著增加 (P <0 .0 1 ) ;而 5 HD +P +I/R组 (52 .88%± 6 .2 5 % )及 5 HD +I/R组 (53 .1 6 %± 5 .35 % )均较P +I/R组明显降低 (P <0 .0 1 )。②以对照组窦房结细胞平均荧光强度值为 1 0 0 % ,其余各组窦房结细胞相对荧光值为 :I/R组 374%± 52 % ,显著高于对照组 (P <0 .0 1 ) ;P +I/R组 1 62 %± 2 0 % ,较I/R组显著降低 (P <0 .0 1 ) ;5 HD +P +I/R及 5 HD +I/R两组分别为 385 %± 56 %与 379%± 44 % ,均较P +I/R组显著增高 (P <0 .0 1 )。结论 :①模拟缺血 再灌注可显著降低窦房结细胞存活率 ,并致窦房结细胞内钙超载 ;②KATP通道     

Proteomics Disclose the Potential of Gingival Crevicular Fluid (GCF) as a Source of Biomarkers for Severe Periodontitis

Periodontal disease is a widespread disorder comprising gingivitis, a mild early gum inflammation, and periodontitis, a more severe multifactorial inflammatory disease that, if left untreated, can lead to the gradual destruction of the tooth-supporting apparatus. To date, effective etiopathogenetic models fully explaining the clinical features of periodontal disease are not available. Obviously, a better understanding of periodontal disease could facilitate its diagnosis and improve its treatment. The purpose of this study was to employ a proteomic approach to analyze the gingival crevicular fluid (GCF) of patients with severe periodontitis, in search of potential biomarkers. GCF samples, collected from both periodontally healthy sites (H-GCF) and the periodontal pocket (D-GCF), were subjected to a comparison analysis using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). A total of 26 significantly different proteins, 14 up-regulated and 12 down-regulated in D-GCF vs. H-GCF, were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The main expressed proteins were inflammatory molecules, immune responders, and host enzymes. Most of these proteins were functionally connected using the STRING analysis database. Once validated in a large scale-study, these proteins could represent a cluster of promising biomarkers capable of making a valuable contribution for a better assessment of periodontitis.     

老年长期下呼吸道感染患者肺泡灌洗液中溶菌酶检测的意义

本文用溶菌板分析法测定了老年人长期下呼吸道感染者肺泡灌洗液(BALF)中溶菌酶(Lym)的水平,发现长期下呼吸道感染的老年人BALF中的Lym明显低于非下呼吸道感染的老年人(P<0.05);同时显示老年非下呼吸道感染者明显低于中青年对照组(P<0.025),中青年下呼吸道感染者明显高于非下呼吸道感染的同龄人(P<0.01)。说明老年人细胞免疫功能显著降低,长期肺部感染时更加重了细胞免疫功能的损害。这可能是老年人易感染、不易治愈和反复发作的原因之一。测定长期下呼吸道感染的老年患者BALF中的Lym有助于判断患者的免疫状况,对疾病的治疗及预后有一定的指导意义。     

Evaluation of Cerebrospinal Fluid for the Presence of Anticardiolipin Antibodies (aCL) in NP-SLE Patients

Many neurological or psychiatric manifestations of SLE (NP-SLE) are related to the presence of anticardiolipin antibodies (aCL) in the patient’s sera. The aim of this study was to evaluate the presence of aCL in cerebrospinal fluid (CSF) in SLE patients with NP features. Fifteen SLE patients were studied, all with NP features. CSF was evaluated for intrathecal IgG synthesis, oligoclonal IgG, and blood–brain barrier impairment. Sera and CSF were tested by ELISA for the presence of aCL-IgG and aCL-IgM with and without β₂ glycoprotein (β₂ GPI) cofactor. CSF and sera of 50 low back pain patients served as controls. Six patients were aCL(+) and nine aCL(–). In all patients the general CSF examination was normal. In all patients the value of indices of intrathecal IgG synthesis were normal but oligoclonal protein was present in the CSF of three patients. In none of the patients was the blood–brain barrier impaired. Neither aCL-IgG nor aCL-IgM was detected in the CSF of any NP-SLE patient. Mean levels of aCL in patients without cofactor β₂ GPI and with cofactor were as follows: for IgG class 0.005 and 0.057 OD (negative); for IgM class 0.004 and 0.024 OD (negative). We could not detect aCL in the CSF of patients with NP-SLE, even if sera were positive for aCL. Received: 6 July 1999 / Accepted: 18 January 2000     

Predictors of the utilization of long-term care (LTC) services among residents in community-based LTC facilities in Taiwan

Identifying the utilization behaviors of LTC residents is necessary in order to forecast the demand and the level of resource use for health services. The purpose of this study is to understand the utilization behaviors and their predictors among residents of community-based LTC facilities in Taiwan. A prospective design was used in this study. Subjects were from six community-based LTC facilities in Beitou district of Taipei, Taiwan. A one-month time sheet was developed comprising subjects’ socio-demographic characteristics, health status, and their use of LTC services. Among five types of LTC services examined in this study, assistance with activities of daily living (ADL) were the most commonly used (mean = 67.3 ± 46.0). ADL score was the strongest predictor of service utilization, accounting for 40% of the total variation in the utilization of personal assistance services (R² = 0.396). The second most commonly used service was skilled-nursing services (mean = 13.3 ± 10.3). The most common skilled-nursing activities were administration of medication (mean = 5.2 ± 3.9) and measuring vital sign measurement (mean = 3.4 ± 2.3). The results provide useful information on how to allocate resources among staff in community-based LTC facilities.     

Myocardial Ischaemia-reperfusion Injury is Attenuated by Intact Glucagon Like Peptide-1 (GLP-1) in the In Vitro Rat Heart and may Involve the p70s6K Pathway

Background and methods Glucagon Like Peptide-1 (GLP-1), one of the most potent incretin hormones, has potential beneficial actions on the ischaemic and failing heart. This study sought to further identify the mechanisms of action of GLP-1 on the ischaemic heart using an in vitro isolated perfused rat heart model of ischaemic-reperfusion injury (measuring infarct size to area of risk (%)) subjected to 35 min regional ischaemia and 2 h reperfusion. To examine the effect of intact GLP-1 we used an inhibitor of GLP-1 breakdown, Valine pyrrolidide (VP). The downstream target of phosphatidylinositol 3-kinase includes the mTOR/p70s6 kinase pathway which was pharmacologically inhibited by rapamycin. Results and conclusion GLP-1 alone did not decrease myocardial infarction (54.4 ± 3.1%). VP alone did not decrease myocardial infarction (52.5 ± 4%). GLP-1 in the presence of VP produced significant reduction in myocardial infarction compared to control hearts (28.4 ± 2.7% vs. 56.4 ± 3.9% vs. P < 0.05). Inhibiting p70s6 Kinase with rapamycin completely abolished GLP-1 induced protection (57.1 ± 4.9% vs. 28.4 ± 2.7% P < 0.05). There was no detectable increase in the phosphorylated p70s6k after either 5 or 10 min of treatment with GLP-1/VP or with VP alone in comparison to control blots. In conclusion we show for the first time that the protective effects of GLP-1 are mediated by intact GLP-1 and can be inhibited by blocking the p70s6 kinase.     

Effect of Hepatic Stimulator Substance (HSS) on Cadmium-Induced Acute Hepatotoxicity in the Rat Liver

The hepatoprotective effect of HSS against cadmium-induced liver injury was investigated. Rats were intoxicated with a dose of cadmium (3.5 mg/kg b.w.). The rats were treated with normal saline (group I) or HSS (100 mg protein/kg b.w.; group II) 2 hr later and killed at different time points. Hematoxylin-eosin (HE) sections were assessed for necrosis, apoptosis, peliosis, mitoses, and inflammatory infiltration. Serum enzyme activities were assayed. Apoptosis was quantified by the Tunel technique. Thymidine kinase activity and the rate of [3H]thymidine incorporation into DNA were also assayed. Necrosis, hepatocyte apoptosis, and peliosis were minimized in HSS-treated rats (group II). Nonparenchymal cell apoptosis and liver regeneration were not quantitively altered in the HSS-treated group, though the time profile was different. HSS protects hepatocytes against cadmium-induced necrosis, apoptosis, and peliosis. Apoptosis was the major type of cell death for nonparenchymal liver cells and strongly correlated with the extent of peliosis. Interactions between hepatocytes and nonparenchymal liver cells seem to be important for the genesis of hepatic trauma in acute cadmium hepatotoxicity.     

Inhibition of Endothelin (ET-1) Induced Pressor Responses by the Endothelin (ETA) Receptor Antagonist FR139317 in the Pithed Rat

The effects of the novel ETA receptor antagonist, FR 139317, on ET-1 induced blood pressure changes were studied in the pithed Sprague-Dawley rat. FR 139317 in a dose of 0.025 mg/kg b.w. had no effect while 0.05-1 mg/kg b.w. dose dependently inhibited the pressor response to an i.v. bolus injection of ET⁶-1 (800 pmoles/kg). While FR 139317 potently inhibited the magnitide and duration of the ET-I induced pressor response, the ETA antagonist did not significantly influence the shortlasting initial depressor response. We conclude that FR 139317 in the pithed rat potently inhibits ET-1 mediated pressor responses and that this agent may become a significant tool to elucidate the putative physiological and pathophysiological role of ETA receptor mediated responses.     

血管紧张素1-7抑制血管外膜成纤维细胞增殖

目的探讨血管紧张素1-7对血管外膜成纤维细胞增殖的影响.方法在培养大鼠血管外膜成纤维细胞中,用血管紧张素Ⅱ和血管紧张素1-7刺激,检测蛋白激酶C、丝裂素活化蛋白激酶及钙调神经磷酸酶活性,以氚标胸腺嘧啶和氚标亮氨酸掺入量反映血管外膜成纤维细胞增殖的指标.结果血管紧张素1-7既能明显抑制基础状态下血管外膜成纤维细胞蛋白激酶C、丝裂素活化蛋白激酶和钙调神经磷酸酶活性(P＜001或P＜0.05),又能抑制血管紧张素Ⅱ刺激下的血管外膜成纤维细胞蛋白激酶C、丝裂素活化蛋白激酶和钙调神经磷酸酶活性(P＜0.01或P＜0.05).血管紧张素1-7能明显抑制血管外膜成纤维细胞氚标胸腺嘧啶和氚标亮氨酸掺入(P＜0.01或P＜0.05);而血管紧张素Ⅱ则促进血管外膜成纤维细胞氚标胸腺嘧啶和氚标亮氨酸掺入(P＜0.01或P＜0.05).血管紧张素1-7还能抑制血管紧张素Ⅱ刺激下的血管外膜成纤维细胞氚标胸腺嘧啶和氚标亮氨酸掺入(P＜0.01或P＜0.05).结论血管紧张素1-7可能通过影响蛋白激酶C、丝裂素活化蛋白激酶和钙调神经磷酸酶信号通路,发挥抑制血管外膜成纤维细胞增殖的作用.