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We aimed to determine the status of iron in mediating oxidant-induced damage to cultured bovine aortic endothelial cells. Chromium-51-labeled cells were exposed to reaction mixtures of xanthine oxidase/hypoxanthine and glucose oxidase/glucose; these produce superoxide and hydrogen peroxide, or hydrogen peroxide, respectively. Xanthine oxidase caused a dose dependent increase of 51Cr release. Damage was prevented by allopurinol, oxypurinol, and extracellular catalase, but not by superoxide dismutase. Prevention of xanthine oxidase-in-duced damage by catalase was blocked by an inhibitor of catalase, aminotriazole. Glucose oxidase also caused a dose-dependent increase of 51Ci release. Glucose oxidase-induced injury, which was catalase-inhibitable, was not prevented by extracellular superoxide dismutase. Both addition of and pretreatment with deferoxamine (a chelator of Fe3+) prevented glucose oxidase-induced injury. The presence of phenanthroline (a chelator of divalent Fe2+) prevented glucose oxidase-induced 51Cr release, whereas pretreatment with the agent did not. Apotransferrin (a membrane impermeable iron binding protein) failed to influence damage. Neither deferoxamine nor phenanthroline influenced cellular antioxidant defenses, or inhibited lysis by non-oxidant toxic agents. Treatment with allopurinol and oxypurinol, which inhibited cellular xanthine oxidase, failed to prevent glucose oxidase injury. We conclude that (1) among the oxygen species extracellularly generated by xanthine oxidase/hypoxanthine, hydrogen peroxide induces damage via a reaction on cellular iron; (2) deferoxamine and phenanthroline protect cells by chelating Fe3+ and Fe2+, respectively; and (3) reduction of cellular stored iron (Fe3+) to Fe2+ may be a prerequisite for mediation of oxidantinduced injury, but this occurs independently of extracellular superoxide or cellular xanthine oxidase-derived superoxide. © 1994 Wiley-Liss, Inc.1

Nitric oxide (NO) reacts with H2O2 to produce a rise in potent luminol-dependent chemiluminescence under neutral pH conditions. We applied this reaction to the continuous detection of NO released from the rat isolated perfused kidney with simultaneous pressure changes. Acetylcholine increased NO release dose-dependently with the pressure reduction. An NO synthesis inhibitor, NG-monomethyl-L-arginine, abolished the release. This inhibition was reversed by the addition of L-arginine.

1. Plasma levels of adenosine were measured in unrestrained, conscious spontaneously hypertensive rats (SHR) to examine the potential role of adenosine, a naturally occurring substance with profound cardiovascular actions, in cardiovascular regulation in these genetically hypertensive rats. 2. We employed a specific and sensitive assay for adenosine based on fluorescent determination of adenine compounds by high performance liquid chromatography. 3. Plasma adenosine concentrations were significantly higher in 13 week old SHR with hypertension than in Wistar-Kyoto rats (0.165 +/- 0.022 vs 0.096 +/- 0.008 mumol/L; P less than 0.05). 4. These observations indicate that plasma adenosine levels are increased in conscious SHR with established hypertension, and also suggest that adenosine may be at least partly involved in the pathophysiology of high blood pressure in SHR.

Histopathologic examination was done on 18 cases after percutaneous ethanol injection therapy (PEIT) for hepatocellular carcinoma. In eight cases, the lesion was treated by PEIT alone; in the other ten cases, PEIT was combined with transcatheter arterial embolization. The lesion was completely necrotic in 13 cases, 90% necrotic in four cases, and 70% necrotic in the rest. In addition, PEIT seemed to be effective against intercapsular, extracapsular, and vascular invasions. In the four cases of incomplete necrosis, the viable cancer tissue remained in small tumor nodules around the main tumor, in portions isolated by septa, or along the edge of the lesion. Therefore, ethanol should be injected not only into the center of the lesion, but also into sites close to its edge. Ethanol did not damage noncancerous liver parenchyma distant from injected sites. Local dissemination of the cancer cells was not found in any case. Therefore, PEIT seems to be a valuable therapy and may be an alternative to surgery in some cases.

Platelet-activating factor (PAF), added to the bathing solution, stimulated the cardiac muscarinic K+ channel (KACh) in the cell-attached patch (no agonist in the pipette). The PAF-induced KACh channel activation was blocked by WEB2086, a PAF-receptor inhibitor, indicating that the PAF-receptor mediated the response. PAF-induced activation was prevented by nordihydroguaieretic acid, a lipoxygenase inhibitor, and AA-861, a 5-lipoxygenase inhibitor, but was not affected by indomethacin, a cyclo-oxygenase inhibitor. The PAF-induced KACh, channel activity disappeared upon formation of inside-out patch. In this inside-out patch, intracellular GTP alone induced maximal channel reactivation, which was inhibited by GDP-βS. These results suggest that 5-lipoxygenase metabolites of PAF-released arachidonic acid cause a persistent stimulation of GK but not the KACh channel itself, resulting in a receptor-independent activation of the KACh channel by GTP.

SUMMARY 1. We examined the effects of metoclopramide (MCP: 10 mg i.v.) on plasma atrial natriuretic peptide (ANP) and aldosterone concentrations (PAC) and the effect of ANP on MCP-induced PAC in four patients with primary glomerular diseases and seven patients with essential hypertension. 2. MCP injection caused no significant changes in plasma ANP. MCP produced a marked increase in PAC without a significant change in plasma renin activity. 3. The increase in PAC induced by MCP injection was markedly attenuated when preceded by the infusion of ANP (25 ng/kg per min). 4. These results suggest that the dopaminergic D2 mechanism is not involved in the regulation of ANP secretion and that ANP modulates the dopaminergic regulation of aldosterone secretion.

Overdrive Suppression of Kent Conduction. A patient with Wolff-Parkinson-White syndrome was described in whom antegrade conduction over the Kent hundle was suppressed after termination of orthodromic tachycardia. A phenomenon indicative of overdrive suppression of conduction occurred after intravenous disopyramide, and tended to be rate and lime dependent. (J Cardiovasc Electrophysiol, Vol. 1, No. 6, pp. 512–516 December 1990)

A noncapturing conditioning stimulus is known to exert inhibitory effect on a subsequent suprathreshold stimulus, while summation occurs rarely in man. The present study was conducted to revaluate whether conditioning stimulus at a relatively low intensity produced inhibition and summation in man. Thirteen patients with various arrhythmias, 47 +/- 19 years old, were studied. Basic ventricular driving stimuli (S1S1 = 600 msec), a conditioning stimulus (Sc), and extrastimulus (S2) were introduced from a catheter electrode. Sc at an intensity of twice the late diastolic threshold inhibited suprathreshold S2 from evoking a response in all 13 patients. The ScS2 interval producing inhibition was from 11 +/- 4 to 38 +/- 26 msec. When Sc preceded S2 by 5 msec, effective refractory period was shortened by 16 +/- 7 msec in 7 of 13 patients, a phenomenon of summation. The present study demonstrates that inhibition and summation are common phenomena with a single conditioning stimulus at relatively low intensities.

A 24-year-old female was seen our hospital because of frequent palpitation. Twelve-leads ECG showed the ventricular tachycardia with left bundle branch block and inferior axis (VT1) with stable hemodynamic, and catheter ablation was performed. VT1 was provoked easily by the infusion of the isoproterenol, and it incessantly appeared. VT1 showed the near-perfect pacemap at the right ventricular outflow tract (RVOT) septum at first, it naturally changed to another VT (VT2) which had larger R wave in the inferior leads, and transitional zone shifted from V2-3 to V3-4. Appearance of the VT2 indicated the existence of the two different exits of the VT. After the termination of the VT1 by the application at the RVOT septum, VT2 began to appear continuously. Pacemap above the pulmonary artery valve showed the same morphologies as VT2, and clear discrete prepotential was identified at this site. Application at this site terminated the VT2, and all of the VTs become impossible to be provoked. We report a case of VT which had separated two exits, and was treated by the applications at each of the two exits.

Wistar rats rendered cirrhotic with carbon tetrachloride excreted significant proteinuria and hematuria. Serum levels of IgA and IgG were significantly elevated in cirrhotic animals. They showed mild mesangial proliferation and immunofiuorescent studies revealed deposits of IgA and IgG predominantly in mesangial areas and along capillary walls. These findings were very similar to those seen in patients with hepatic cirrhosis or IgA nephropathy. The deposits of IgA were also found in hepatic tissue from cirrhotic animals. The intensity and distribution of glomerular IgA deposits were not diminished after treatment with acid buffer. These results suggest that glomerular IgA are IgA polymers and decreased hepatic clearance of hepatic IgA polymers may be responsible for the glomerular deposition of IgA. ACTA PATHOL. JPN. 35: 561–567, 1985.

INOUE, H., et al.: Summation and Inhibition by Ultrarapid Train Pulses in Dogs: Effects of Frequency and Duration of Trains, Lidocaine, and Beta Blockade To test whether summation and inhibition of excitation hy uitrarapid train pulses were modified by frequency and duration of trains, using lidocaine and beta blockade, the strength-interval relationship was determined with a single extrastimulus and train pulses (100 and 200 Hz) in 28 anesthetized, open-chest dogs. The effective refractory period (ERP) determined at 5 mA was shorter for trains than for single stimulus (summation). Summation determined at 15 mA increased progressively as the duiation of trains was increased to 50 msec after which it reached a plateau. ERP determined at 2 mA was longer with train pulses than with single stimulus (inhibition). Inhibition for 200 Hz trains increased linearly with train duration up to 200 msec, while for 100 Hz trains it became constant when the duration was 80 msec. Lidocaine fplasma concentration; 2.6 ± 1.0 μg/mL) did not affect inhibition and summation in 11 dogs. Propranolol (1 mg/kg, iv) increased summation at 15 mA (n = 7,30 ± 10 vs 46 ± 11 msec with 100 Hz trains, P < 0.01), but did not afect inhibition (37 ± 26 vs 29 ± 17 msec, NS). In conclusion, (1) effect of frequency of train pulses was more on inhibition than on summation; (2) lidocaine did not affect inhibition and summation; and (3) propranolol increased summation but not inhibition.

The authors report the case of a 45 year old woman in whom the diagnosis of nodular regenerative hyperplasia of the liver was made by needle biopsy of the liver, laparoscopy and hepatic venography. The patient did not have any underlying disorders and had not ingested any of the many drugs and chemicals which may produce the lesion. Clinical manifestations were hepatosplenomegaly, portal hypertension and iron deficiency anaemia, and her condition remains unchanged 5 years after diagnosis.