Angiotensin-Converting Enzyme and Endothelial Nitric Oxide Synthase Polymorphisms in Patients with Atrial Fibrillation

GENSINI, F., et al. ; Angiotensin-Converting Enzyme and Endothelial Nitric Oxide Synthase Polymorphisms in Patients with Atrial Fibrillation. Experimental studies have shown a significant increase in angiotensin-converting enzyme (ACE) expression in atrial tissue of AF patients. ACE regulates the synthesis of endothelial nitric oxide (NO), which modulates autonomic nervous activity involved in the development of AF. The aim of the study was to evaluate the prevalence of ACE insertion/deletion and endothelial NO synthase (eNOS) T-786C, G894T, and 4a/4b polymorphisms in 148 patients with persistent AF, compared with 210 control subjects. ACE insertion/deletion polymorphism genotype distribution and allele frequency were significantly different between patients and controls (   P < 0.0001   and   P < 0.0001   , respectively). ACE DD genotype was significantly associated with the risk of AF   (OR DD/ID + II = 3.24, P < 0.0001)   . Analysis of eNOS polymorphisms showed no significant difference in genotype distribution and allele frequency between patients and controls. The results suggest a possible role of ACE DD genotype as a predisposing factor to AF and a pathophysiological mechanism of ACE inhibition in reducing the incidence of AF in patients with left ventricular dysfunction. (PACE 2003; 26[Pt. II]:295–298)     

Flecainide Test in Brugada Syndrome: A Reproducible but Risky Tool

GASPARINI, M., et al .: Flecainide Test in Brugada Syndrome: A Reproducible but Risky Tool. The flecainide test is widely used in Brugada syndrome. However, its reproducibility and safety remain ill-defined. This study included 22 patients (18 men, mean age 34 years). Mutations in the SCN5A gene were found in eight patients. Two patients had aborted sudden cardiac death, 8 had syncope/presyncope, and 12 were asymptomatic. The ECG was diagnostic in 19 patients and suggestive in 3. At baseline, 21 of 22 patients underwent a flecainide test (2 mg/kg IV bolus over 10 minutes). In 21 of 21 patients the test was diagnostic or amplified the typical ECG pattern. At the end of drug infusion, sustained VT lasting 7–10 minutes developed in two patients. A second flecainide test was performed within 2 months in 20 patients. The test was not repeated in the two patients with prior development of VT. The flecainide test was diagnostic in 20 of 20 patients. Sustained VT occurred in one patient and recurrent VF in another. The reproducibility of the flecainide test was 100%. In 4 (18%) of 22 patients major VAs were documented after the end of flecainide infusion. VA occurred in 3 (43%) of 7 patients with, versus 1 (7%) 15 without SCN5A gene mutation (P < 0.05). No diagnostic ECG changes or arrhythmias developed in 25 control patients without structural heart disease who underwent the same study protocol. This study shows a high flecainide reproducibility, supporting its diagnostic value in Brugada syndrome. However, the occurrence of major VA, significantly higher in patients with documented SCN5A gene mutation, including in asymptomatic patients, mandates the performance under appropriate medical supervision. Whether a slower rate of drug infusion can lower the risk of VA induction, while maintaining the sensitivity of the test should be explored. (PACE 2003; 26[Pt. II]:338–341)     

CONSTANT ABSOLUTE ETHANOL INTAKE BY SARDINIAN ALCOHOL-PREFERRING RATS INDEPENDENT OF ETHANOL CONCENTRATIONS

The present study was designed to evaluate ethanol drinkingbehaviour in Sardinian alcohol-preferring (sP) and Sardinianalcohol-non-preferring (sNP) rats in the presence of differentethanol concentrations. Ethanol intake was tested under thetwo-bottle, free-choice regimen and continuous access schedule.Ethanol-naive sP and sNP rats were initially given ethanol solutionat the standard, constant concentration of 10% (v/v) for 8 consecutivedays (Phase 1). As expected, daily ethanol intake in sP ratsrose from 4 to {small tilde}l6g/kg; in contrast sNP rats consumed<10g/kg/day ethanol. Subsequently, an ascending series ofethanol concentrations, ranging from 3 to 60% (v/v), was presentedto sP and sNP rats over a 28-day period (Phase 2). At concentrationsvarying from 7 to 30%, sP rats consumed constant amounts ofabsolute ethanol per kg of body weight ({small tilde}6.0 g/kg/day).Daily ethanol intake in sNP rats remained constantly lower than1.0 g/kg, irrespective of the ethanol concentration. Data fromPhase 2 demonstrate the ability of sP rats to precisely adjustdaily ethanol intake and support the hypothesis that voluntaryethanol drinking in sP rats is sustained by specific pharmacologicaleffects of ethanol.     

DIFFERENT AFFINITY OF CORTICAL GHB BINDING SITES IN SARDINIAN ALCOHOL-PREFERRING (sP) AND-NON PREFERRING (sNP) RATS

Specific gamma-hydroxybutyric acid (GHB) binding sites in corticalmembranes of selectively bred alcohol-preferring sP and alcohol-nonpreferring sNP rats were compared using [2,3³H]GHB ligand. ThesP rat line showed an increased affinity (-40% lower K_d) ofboth the high- and low-affinity sites in comparison with thesNP line. No significant difference in GHB receptor density(B_max) was detected between the two rat lines. The results raisethe possibility that differences in GHB binding sites may playa role in the genetic predisposition to ethanol preference inour rat line.     

Synthetic homo-oligomethionine chemoattractants

Using solution methods, we have synthesized several series of L-methionine homooligopeptides from the dipeptide to the hexapeptide with either a free α-carboxyl function or different C-blocking groups (methoxy, benzyloxy, benzy-lamino) and with N-blocking groups of either the amide type (formyl, pivaloyl) or the urethane type (tert.-butyloxycarbonyl). Compounds were compared to determine the combined effect of main-chain length and presence and nature of N- and C-blocking groups on conformation-activity relationship. Each peptide was tested for its ability to induce rabbit peritoneal polymorphonuclear leukocytes in the presence of cytochalasin B to secrete granule enzymes. In parallel, a conformational analysis was carried out in the solid state and in solution, using infrared absorption and circular dichroism. The biological and conformational data are discussed in relation to a recently proposed model of the chemotactic peptide receptor of rabbit neutrophils.     

Allyl ester as temporary protecting group for the β-carboxy function of aspartic acid

The use of the allyl ester as a temporary protecting function in aspartyl peptides is described. The β-allyl ester was introduced into Boc-Asp-Phe-NH₂ 4a, Boc-Asp-Gly-NH₂ 4b and Boc-Asp-Ser-NH₂ 4c by means of the caesium salt method. It was removed from these molecules 5 using noble metal catalysts under weakly basic, acidic or even neutral conditions likewise in high yield. The formation of an aminosuccinyl derivative during the deblocking reactions was not observed. Treatment of the dipeptide Boc-Asp(OAll)-AS-NH₂ with an excess of triethylamine at room temperature induced the ring closure to the cyclic imide.     

Long-Term Restenosis After Multiple Stent Implantation: A Quantitative Angiographic Study

Elective high pressure stent implantation in focal coronary lesions has a high procedural success and low incidence of restenosis in comparison with balloon angioplasty. For the treatment of diffusely diseased coronary arteries, however, a high incidence of subacute thrombosis and late restenosis has been reported. The aim of this study was the prospective evaluation of procedural and long-term outcome after implantation of multiple stents. In a consecutive series of 48 patients, 48 lesions were treated with the implantation of 120 stents (2.5 ± 1.0 stents/lesion). Stent implantation was performed electively in 15%, for dissection in 56%, and for suboptimal balloon angioplasty result in 29% of patients. The lesion length before stenting, including balloon angioplasty induced dissections, was 28.5 ± 9.8 mm (range 20–62), the mean length of the stented segment was 40 ± 16 mm. The procedure was successful in 45 patients (95%). Procedural related complications included two urgent bypass operations (4%) and one transmural myocardial infarction (2%). Two subacute stent thrombosis events (4%) occurred, both in-hospital, 1 and 3 days after implantation. Follow-up was obtained in 43 eligible patients at 6.4 ± 1.3 months, revealing an overall restenosis rate of 30% (13 patients). Quantitative angiography (CAAS II, edge detection algorithm) showed a minimal lumen diameter of 0.93 ± 0.28 mm (diameter stenosis 62%± 13%) before treatment, 2.81 ± 0.26 mm (diameter stenosis –4 ± 13%) after stenting, and 1.79 ± 0.58 mm (diameter stenosis 30%± 20%) at follow-up. Predictors of restenosis were not identified. Thus, multiple stent implantation has high procedural success and the late restenosis of long lesions after multiple stents compares favorably with balloon angioplasty.     

Invasive cervical cancer in young women

Summary. Between 1970 and 1979, 103 women below 35 years of age with invasive cervical cancer were treated at the First Obstetrics and Gynaecology Clinic of the University of Milan. Nine patients were pregnant or less than 3 months postpartum. Estimated 10–year disease–free survival, determined by the life–table method, was 100% in stage IA (37 patients), 79% in stage IB (45 patients), 67% in stage 11 (15 patients), 0% in stages III (5 patients) and IV (1 patient). Prognosis was also strongly associated with lymph–node involvement, 10–year actuarial survival decreasing from 93% in lymph–node–negative to 44% in lymph–node– positive patients ( P 相似文献   

Synthesis,purification and conformational studies on enkephalin derivatives containing Λ-amino-n-butyric acid

The solid-phase synthesis of several analogs of enkephalin containing Λ-amino-butyric acid is reported. Synthetic strategies, purification methods, chemical and physicochemical characterization are discussed. The n.m.r. data suggest for some of the analogs structural features similar to the opioids.