Sensory neuropeptides are not directly involved in bronchial hyperresponsiveness induced by interleukin-8 in guinea-pigs in vivo

Background Interleukin-8 (IL-8) hus been shown to be a chemotactic factor for netitrophils, T-lymphocytes and eosinophils. Repeated intranasal administration of IL-8 enhances bronchial responsiveness to inhaled histamine in guinea-pigs. Neuropeptides which arc released trotn C-fibre nerve-endings have been postulated to induce bronchial hyperresponsiveness through neurogenic inflammation. Objective This study was conducted to examine whether sensory neuropeptides are involved in the IL-8-induced bronchial hyperresponsiveness. Methods IL-8 at a dose of 5μg/kg was administered intranasally to guinea-pigs twice a week for 3 weeks. One day after the last administration, animals were anesthetized and artificially ventilaled through tracheal cannula, and lateral pressure at the tracheal cannula (Pao) was measured as an overall index of airway responses lo increasing concentrations of inhaled histamine (25, 50, 100, and 200 μg/mL). A NKI and NK2 dual antagonist FK224(10mg/kg), a selective NK1 antgonist FK888 (10mg/kg) or vehicle was intravenously administered 10min before measurement of bronchial responsiveness. Result The IL-8 treatment significantly enhanced bronchial responsiveness to histamine (ANOVA P < 0.01). FK224 or FK888 did not alter the IL-8-induced bronchial hyperresponsiveness. Conclusion We conclude that repeated intranasal administratioti of IL-8 causes bronchial hyperresponsiveness (BHR) and that neuropeptides such as neurokinin A and substance P do not directly contribute to the development of BHR induced by IL-8.     

Functional role and histological demonstration of nitric-oxide-mediated inhibitory nerves in dog sphincter of Oddi

Abstract Nitric oxide (NO) plays an important physiological role in regulating gastrointestinal motility. Involvement of endogenous NO was evaluated in the response to non-adrenergic, non-cholinergic (NANC) nerve stimulation of the dog sphincter muscle of Oddi. Transmural electrical stimulation (TES), nicotine (10^?5M) and K⁺ (10 mM) produced only a relaxation in the sphincter muscle strips contracted with substance P, which was not potentiated by atropine. The TES-induced relaxation was abolished by tetrodotoxin (3 times 10^?7 M) and oxyhaemoglobin (1.6 times 10^?5 M), but not affected by atropine (10^?7 M), propranolol (10^?7 M), phentolamine (10^?7 M), indomethacin (10^?6 M), chole-cystokinin (CCK, 10^?8 M) and vasoactive intestinal polypeptide (VIP, 10^?8 M). The relaxation was also abolished by treatment with N^G-nitro-L-arginine (L-NA, 10^?5 M), an NO synthase inhibitor. Nicotine produced a transient relaxation, which was abolished by tetrodotoxin, hexamethonium (10^?5 M) and L-NA, but not affected by atropine and N^G-nitro-D-arginine (D-NA, 10^?5 M). The addition of K⁺ elicited a transient relaxation, which was abolished by tetrodotoxin and L-NA. The inhibitory effects of L-NA were antagonized by L-arginine (10^?3 M). The presence of neurons containing nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase was histochemically demonstrated in the sphincter of Oddi. These findings may indicate that TES, nicotine and K⁺ liberate NO from NANC inhibitory nerve which is involved in the relaxation of the dog sphincter of Oddi. The muscular tone does not seem to be regulated by cholinergic nerves under the experimental conditions used.     

Role of sensory neuropeptides in post-allergic propranolol-induced bronchoconstriction in guinea pigs in vivo

Background Administration of propranolol can provoke bronchoconstriction in asthmatic patients. We hypothesized that such bronchoconstriction may result from the inflammatory mediators released by an allergic reaction. We recently developed a guinea pig model for propranolol-induced bronchoconstriction (PIB). Neuropeptides which are released from C-fibre nerve endings have been postulated to induce bronchial hyperresponsiveness through neurogenic inflammation. Objective The purpose of this study was to examine whether sensory neuropeptides are involved in the development of PIB after allergic reaction. Methods Propranolol at a concentration of 10mg/ml was inhaled 20min after antigen challenge in passively sensitized, anaesthetized and artificially ventilated guinea pigs. The animals were treated intravenously with a NK₁ and NK₂ dual antagonist, FK224, in a dose of 1 or 10 mg/kg or vehicle or a selective NK₁ antagonist, FK888, in a dose of 1 or 10mg/kg or vehicle 10min before or 15min after antigen challenge. Results Propranolol inhaled 20 min after antigen challenge caused bronchoconstriction. FK224 or FK888 administered 15 min after antigen challenge as well as 10 min before antigen challenge did not reduce the PIB. Conclusion We conclude that neuropeptides such as neurokinin A and substance P do not directly contribute to the development of PIB after allergic reaction.     

Different transformation of mature teratoma in a patient with mixed germ cell tumor of the testis

A 44-year-old male was referred with a left supraclavicular lymphadenopathy. A biopsy of the lymph node showed metastatic embryonal carcinoma. Tumor markers were present at high levels: alpha-fetoprotein 253.9 ng/mL, beta-human chorionic gonadotrophin 62 ng/mL. Computed tomography (CT) showed retroperitoneal adenopathy. High orchiectomy was done. The patient was treated with three cycles of etoposide plus cisplatin, achieved normalization of the serum tumor markers and underwent retroperitoneal lymph node dissection. Pathological findings of multiple lymph nodes showed teratomatous glands without viable cells. At follow-ups performed every 3 months, tumor markers remained within normal limits and no evidence of recurrence was observed. Eight years after first admission a CT scan revealed a cystic tumor 1 cm in diameter in the para-aortic region. The cystic tumor continued to slowly grow, expanding by 1 cm in diameter per year without elevation of tumor markers. The para-aortic tumor had grown to 4 cm in diameter and a left supraclavicular lymphadennopathy recurred. A resection of the supraclavicular cystic tumor showed mucinous cystadenocarcinoma, but a cystic tumor in the para-aortic region revealed mature teratoma. Here we report a case of mature teratoma with metastases at supraclavicular and para-aortic lymph nodes which had different transformations in spite of both regions consisting of cystic tumors.     

Variant Preexcitation Syndrome: A True Nodoventricular Mahaim Fiber or an Accessory Atrioventricular Pathway with Decremental Properties?

WPW Variant. Introduction: The differentiation between a nodoventricular fiber and an accessory atrioventricular (AV) pathway with long conduction times and decremental properties could he very difficult even at detailed electrophysiologic study.
Methods and Results: A 20-year-old male with a history of a wide QRS tachycardia underwent electrophysiologic study. Baseline intervals were normal. There was evidence of dual AV pathways, and a sudden increase in AH interval was associated with the emergence of a delta wave. The atrio-delta interval showed a progressive prolongation. The preexcited QRS complex was typical of a posteroseptal pathway, and the earliest ventricular activation site was recorded at the posteroseptal region. Retrograde conduction was exclusively over the normal conduction system. During ventricular extrastimulation, a sudden increase in HA interval was associated with anterograde conduction over the accessory pathway. The intervals between the stimulus artifact and the onset of the delta wave during atrial pacing from two atrial sites (S-Delta) were compared with those between the retrograde atrial electrogram on the His channel and the onset of the delta wave during ventricular pacing (A2_HB-Delta). When pacing from the proximal coronary sinus, the shortest S-Delta interval did become shorter than the longest A2HK-Delta interval (155 vs 170 msec).
Conclusion: The finding that the S-Delta interval could become shorter than the A2_HB-Delta interval provides strong evidence that this accessory pathway was not connected to the AV node hut arose directly from the atrial tissue of the posteroseptal region.     

The Effect of Biliary Pressure on Antibiotic Excretion into Bile

Abstract: Biliary obstruction has been recognized to inhibit excretion of antibiotics into bile. In the present study, using cefpirome sulfate (CPR), we sought to determine the effect of biliary pressure on antibiotic transfer into bile in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). Thirty-six patients with a variety of biliopancreatic diseases (free of renal disease or hypoproteinemia) received a single intravenous dose of CPR (1 g) prior to ERCP. Under fluoroscopy a diagnostic catheter with a metal ball tip was advanced into the middle portion of the extrahepatic bile duct or, in cases of common bile duct obstruction, above the obstruction. Biliary pressure was measured via the same catheter using duodenal pressure as a reference. Subsequently, bile was aspirated, and blood was withdrawn simultaneously. The mean interval between CPR administration and the bile and blood samplings was 67±12 minutes. The bile CPR concentration and the bile/serum ratio of CPR concentrations showed a significant inverse correlation with biliary pressure, but the serum CPR concentration did not. The bile CPR concentration and the bile/serum ratio of CPR concentrations differed significantly between the group with normal biliary pressures, below 10 mmHg, and that with biliary pressures exceeding 10 mmHg. The serum CPR concentrations of the two groups were similar. These results suggest that biliary pressure plays an important role in determining antibiotic transfer into bile.     

Quantitative Analysis of Concealed Conduction into Accessory Atrioventricular Pathways in Wolff-Parkinson-White Syndrome

Concealed conduction is demonstrated to occur in an accessory AV pathway (AP). To test the hypothesis that anterograde and retrograde concealed conduction in the AP would have different characteristics, 35 consecutive patients with single APs were studied. The anterograde or retrograde ERP of the AP could be determined in 23 of those patients. Anterograde concealed conduction in the AP was assessed in the first 13 patients with retrograde AP conduction (8 APs with retrograde conduction only and 5 with both directions) (group A). Retrograde concealed conduction in the AP was evaluated in the remaining 10 patients with anterograde AP conduction (6 APs with anterograde conduction only and 4 with both directions) (group B). The concealed conduction in the AP was quantified by determining the ERP of the AP using a “probe” extrastimulus (S_p) introduced in the opposite chamber. The ERP was determined both during conventional extrastimulus (S₁S₂ method; ERP_c) and during that with an S_p (S₁S_pS₂ method; ERP_p). The S_p was delivered before or after the last S₁ with various S₁S_p intervals. The ERP_p was determined at each S₁S_p interval. Three distinct patterns in concealed conduction in the AP were noted. In the first pattern, the ERP_p was always shorter than the ERP_c, whereas the reverse relation was noted in the second pattern. The third pattern showed a combination of the two. In group A, only the first pattern was noted. In group B, the first, second, and third patterns were noted in 4, 2, and 4 patients, respectively. The first pattern was noted only in septal APs and the second and third were seen only in left free-wall APs. The second pattern was seen in patients with retrograde AP conduction, whereas the third one was mainly noted in patients without retrograde AP conduction. These observations indicate that anterograde and retrograde concealed conduction in the AP have different characteristics. Shortening of the ERP_p might be due to the “peeling back” phenomenon, and its lengthening might be caused by the presence of the inhomogeneous refractory periods of the AP. (PACE 1997; 20[Pt. I]:1342-1353)     

Endoscopy-Assisted Radiofrequency Ablation Around the Coronary Sinus Ostium in Dogs:

Endoscopy for Ablation Around the CS Ostium. Introduction : Radiofrequency ablation of the slow pathway can prolong atrioventricular (AV) nodal properties and RR intervals during atrial fibrillation (AF) in many patients with AV nodal reentrant tachycardia. However, it is not well elucidated whether these changes are related to the presence of dual AV nodal pathway physiology. The aim of this study was to evaluate changes of AV nodal properties and RR intervals during AF caused by ablation of two specific areas in dogs.
Methods and Results : Assisted by fiberoptic endoscopy, linear lesions were created between the coronary sinus ostium and tricuspid valve annulus (area 1) or posterior to the ostium (area 2) in 15 dogs. Three additional dogs served as controls. The measurements were made under autonomic blockade. Catheter ablation could be assisted in all dogs by means of endoscopy. Linear lesions were confirmed at autopsy. AV nodal parameters and RR intervals showed no overall changes. Individual data showed that ablation of area I resulted in modification of AV nodal properties in 54.5% (facilitation in 363% and inhibition in 18.2%), whereas ablation of area 2 induced changes in 50% (facilitation in 10% and inhibition in 40%). The RR intervals were shortened in 33.3% and 20% and prolonged in 44.5% and 40% after ablation of areas 1 and 2, respectively. The RR intervals during AF correlated well with the Wenckebach cycle length and the AV node functional refractory period before and after ablation (r = 0.78 to 0.94, P < 0.01 for each).
Conclusions : Ablation of the two specific areas around the coronary sinus ostium was equally effective in modifying AV nodal properties and the ventricular response during AF without dual AV nodal pathway physiology. The ventricular rate to AF after ablation correlated well with the residual AV nodal properties.