Chymase-like angiotensin II-generating activity in end-stage human autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by exuberant inflammation and fibrosis, a process believed to contribute to progressive loss of normal renal function. Despite early-onset hypertension and intrarenal renin/angiotensin II (AngII) activation, angiotensin-converting enzyme (ACE) inhibition does not consistently confer renal protection in ADPKD. The hypothesis was that mast cells within the inflammatory interstitium release chymase, an enzyme capable of efficient conversion of AngI to AngII, providing an ACE-independent route of AngII generation. End-stage ADPKD renal tissue extracts and cyst fluids were assayed for time-dependent, chymostatin-inhibitable conversion of (125)I-AngI to (125)I-AngII under conditions of ACE and aminopeptidase inhibition by means of HPLC. Thirteen of 14 ADPKD kidney extracts exhibited chymase-like AngII-generating capacity; calculated initial reaction rates averaged 3.9 +/- 2.9 fmol AngII/min/ micro g protein with a mean maximal conversion of 55% +/- 30% of added substrate. AngII-generating activity was both protein and substrate dependent. All five cyst fluid samples were negative. Chymase-like activity was detectable in only three of six non-ADPKD kidney extracts. Immunoreactive chymase protein was present in/around mast cells within the fibrotic renal interstitium in all samples. Findings demonstrate for the first time the presence of mast cells, mast cell-associated immunoreactive chymase protein, and chymase-like AngII generating capacity in ADPKD cystic kidneys. Results support the potential for ACE-independent AngII generation and for mast cell-initiated inflammatory processes in ADPKD, each with therapeutic implications for ADPKD renal progression.     

3,4-二氯苯丙烯酰另丁胺对大鼠脑缺血-再灌注损伤的影响

目的：研究新的桂皮酰胺类衍生物,３－４二氯苯丙烯酰另丁胺（ＡＥＤ８８０１）对大鼠脑缺血／再灌注损伤的影响。方法：采用Ｐｕｌｓｉｎｅｌｌｉ四血管阻断大鼠脑缺血／再灌注模型,观察了ＡＥＤ８８０１对脑组织中水含量、氨基到含量、６－ｋｅｔｏ－ＰＧＦ１α和ＴＸＢ２含量,以及二者之比值的影响。结果：一ＡＥＤ８８０１能够降低脑缺血／再灌注大鼠所引起的脑水含量增加。二采用氨基酸自动分析仪进行检测,发现脑缺血／再灌     

Ethanol Administration Diminishes the Endotoxin-induced Increase in Glucose Metabolism

The metabolism of ethanol (ETOH) is known to increase the cytosolic NADH/NAD ratio and consequently impairs hepatic glucose output in the fasted state. In contrast, one of the characteristic alterations in glucose metabolism produced by the administration of endotoxin is an increase in the de novo synthesis of glucose. Therefore, the present study tests the hypothesis that the acute administration of ETOH will prevent the endotoxin-induced increase in glucose production. In vivo glucose kinetics were determined by the infusion of [6-3H, U-14C]glucose in catheterized conscious rats. The intravenous infusion of tracer glucose, and ETOH (100 mg/100 g b.w./hr) or saline were started at the same time and both continued throughout the experiment. Two hours later the ETOH infusion rate was decreased to maintain the blood ETOH levels between 100 and 160 mg/dl. At 140 min, endotoxin (100 micrograms/100 g b.w.) was injected. ETOH alone did not alter basal values of plasma glucose (5 mM), glucose rate of appearance (Ra; 35 mumols/min/kg) or metabolic clearance (MCR; 7 ml/min/kg). Endotoxin alone increased plasma glucose (80%) and lactate (140%) concentrations, glucose Ra (60%) and recycling (40%) in saline-infused rats, whereas in ETOH-infused animals, plasma glucose and lactate levels were only elevated 40% and glucose Ra and recycling were unchanged. The results show that acute ETOH administration diminishes the increased glucose production and utilization seen in endotoxemia. The attenuation of the endotoxin effect by ethanol is due to inhibition of hepatic glucose production and peripheral glucose utilization.     

Myometrial invasion by endometrial carcinoma: sonographic assessment

The depth of myometrial invasion by endometrial carcinoma was evaluated using real-time sonography (US) in 20 patients with histologically proved adenocarcinoma of the endometrium. In 14 of 20 (70%) cases, US-based estimation of the depth of myometrial invasion was within 10% of the actual measurement in the gross specimen. The US-based estimation of tumor invasion was low in seven patients, high in four patients, and agreed with pathologic findings (+/- 5%) in nine patients. In four patients with polypoid intraluminal extension of tumor, a deeply invasive tumor was suspected on US but was not found on pathologic examination. In 12 superficially invasive tumors, the continuity of the demarcating subendometrial halo was intact in nine and incomplete in three. In six patients with deeply invasive tumors, this zone was partially disrupted in four, totally disrupted in one, and intact in one. Errors of estimation of the depth of myometrial invasion on US most frequently occurred when a tumor had a significant intraluminal polypoid extension. Demonstration of a subendometrial halo usually indicated superficial invasion, whereas the absence of a halo was frequently associated with deep invasion.     

International Headache Society classification: interobserver reliability in the diagnosis of primary headaches

We assessed interobserver reliability of the International Headache Society (IBIS) classification for diagnosis of primary headaches. The study was performed on 103 patients consecutively seen at two Headache Centres. Each patient was given a structured interview recorded on videotape. Four experienced clinicians then reviewed the interviews separately and made a diagnosis of headache according to IHS criteria at the one- and two-digit levels. At both the one- and the two-digit level the agreement was substantial (Kappa = 0.74 and 0.65, respectively). The analysis of reliability for each of nine items necessary for diagnosis showed an agreement ranging from substantial (Kappa = 0.69) to almost perfect (Kappa = 0.89). Our results indicate that the IHS classification has a good reliability for the diagnosis of primary headaches at the one- and two-digit levels.