Radiofrequency Catheter Ablation for AV Nodal Reentrant Tachycardia Associated with Persistent Left Superior Vena Cava

Slow A V nodal pathway ablation using RF is highly effective for patients with refractory A V nodal reentrant tachycardia (AVNRT). We report three catheter ablation cases using RF current in patients associated with persistent left superior vena cava (PLSVC). Three patients with drug refractory AVNHT of common variety were involved in this study. An electrode catheter introduced through the left subclavian vein inserted directly into the coronary sinus, a typical anatomical finding of PLSVC. The ablation procedure was initially performed at the posteroinferior region of Koch's triangle. A slow pathway potential could not be found from that area; nonsustained junctional tachycardia (NSJT) did not occur during the delivery of RF current; there was failure to eliminate slow AV nodal pathway conduction. The catheter then was moved into the bed of the proximal portion of the markedly enlarged coronary sinus. A slow AV nodal pathway potential was recorded through the ablation catheter, and the delivery of RF current caused NSJT in two patients. Complete elimination of slow AV nodal pathway conduction was accomplished in these two patients by this method. No adverse effects were provoked by this procedure. Catheter ablation of the slow A V nodal pathway guided by a slow pathway potential and the appearance of NSJT was feasible and safe in the area of the coronary sinus ostium in patients associated with PLSVC.     

Conformation and complexation with metal ions of cyclic hexapeptides: cyclo (l-Leu-l-Phe-l-Pro)2 and cyclo (l-Cys(Acm)-l-Phe-l-Pro]2

Cyclic hexapeptides, cyclo (l -Leu-l -Phe-l -Pro)₂ and cyclo[l -Cys(Acm)-l -Phe-l -Pro]₂, in which Acm represents an acetoamide-methyl group, were synthesized, and the conformation and complexation with metal ions were investigated. Cooperation of the carbonyl groups of the Cys(Acm) side chains with those of the cyclic skeleton in complexation was especially examined. Cyclo(l -Leu-l -Phe-l -Pro)₂, which possesses no functional groups on side chains, was taken as the reference compound. ¹³C- and two-dimensional n.m.r. measurements revealed that cyclo(l -Leu-l -Phe-l -Pro)₂ and cyclo[l -Cys(Acm)-l -Phe-l -Pro]₂ took a C₂-symmetric conformation contaIntng cisl -Phe-l -Pro bonds in chloroform and acetonitrile. Both cyclic hexapeptides were found to complex selectively with Ba²⁺ and Ca²⁺ in acetonitrile. On complexation the conformation of either cyclic hexapeptide changed into a similar one. However, the binding constant of cyclo[l -Cys(Acm)-l -Phe-l -Pro]₂ was higher than that of cyclo(l -Leu-l -Phe-l -Pro)₂. The n.m.r. measurements showed that the amide carbonyl groups of Cys(Acm) side chains as well as those of cyclic skeleton in cyclo[l -Cys(Acm)-l -Phe-l -Pro], cooperatively bound the cations.     

Binding of enkephalin/dextran conjugates to opioid receptors

[ala²]Enkephalin molecules were connected to dextran, and the affinities of the enkephalin/dextran conjugates for opioid receptors were studied. Two kinds of enkephalin derivatives, YaGFLGK-NH₂ and YaGFLGS′S′PS′S′PS′KP-OMe (S'represents a Sar residue) were prepared. They retained the high affinity of the enkephalin unit toward opioid receptors. On the other hand, receptor affinity of the enkephalin derivative dextran conjugates became lower than that of the enkephalin derivatives. Fluorescence from the Tyr residue of the conjugates in a buffer solution was less quenched by succinimide than that of the enkephalin derivatives. Therefore, in these conjugates, the binding of the enkephalin moieties to receptors should be hindered by a steric effect of the dextran matrix. However, the receptor affinity (as defined on the basis of an enkephalin unit) increased on increasing the amount of enkephalin units connected to the dextran matrix, especially in the case of the connection through a shorter spacer arm, suggesting simultaneous binding to a few receptors by the conjugate.     

Synthesis and interaction with metal ions of cyclic oligopeptides bearing carboxyl groups

Cyclic di- and tetrapeptides bearing carboxyl or carboxylate groups, cyclo[Glu(OBzl)-Glu(OMe)], cyclo [Glu-Glu(OMe)], cyclo(Glu-Glu), cyclo[Glu(OMe)-Pro)₂ and cyclo(Glu-Pro)₂ were synthesized and investigated on the intramolecular interaction of carboxyl side chains in the complexation with metal ions in relation with the conformation. The three kinds of cyclic dipeptides were found to take a flagpole boat conformation. Folded conformation of side chains was predominant for cyclo[Glu(OBzl)-Glu(OMe)] and cyclo[Glu-Glu(OMe)]. However, cyclo(Glu-Glu) took an unfolded conformation. Intramolecular interaction of carboxyl groups was observed neither in free state nor in complexation with metal ions. The intramolecular interaction of carboxyl groups was observed in the case of cyclo(Glu-Pro)₂ in the absence of metal ions added. Cyclo[Glu(OMe)-Pro], and cyclo(Glu-Pro)₂ formed a complex with Ca²⁺ and Ba²⁺ without participation of side chains.     

Preliminary Phase I Study of Human Leukocyte Interferon: Side Effects of the Interferon

Human leukocyte interferon was administered systematically to13 Japanese patients and its side effects were evaluated. Systemicadministration of interferon caused a temporary febrile responsein most of the patients. Intravenous injection caused a moresevere but shorter response than intramuscular injection. Thelong-term administration of interferon caused an increase inneutrophils for one or a few months in six patients. No otherside effects were found in any of the patients. Because theside effects may be due to the impurity of the interferon preparations,more highly purified interferon should be used from now on.     

Sirtuin 1 activator SRT1720 suppresses inflammation in an ovalbumin‐induced mouse model of asthma

Background and objective: In asthma, reduced histone deacetylase activity and enhanced histone acetyltransferase activity in the lungs have been reported. However, the precise function of Sirtuin 1 (Sirt1), a class III histone deacetylase, and the effect of the Sirt1 activator SRT1720 on allergic inflammation have not been fully elucidated. Methods: The effect of SRT1720, a synthetic activator of Sirt1, in an ovalbumin (OVA)‐induced asthma mouse model was investigated. The effect of SRT1720 and resveratrol on OVA stimulation in splenocytes from OVA‐sensitized and challenged mice was also examined. Results: In OVA‐sensitized and challenged mice (OVA mice) compared with saline‐sensitized and challenged mice (control mice), Sirt1 messenger RNA expression in the lungs was decreased (P = 0.02), while cellular infiltration, airway eosinophilia and bronchoalveolar lavage (BAL) fluid levels of interleukin (IL)‐4, IL‐5 and IL‐13 were increased (P < 0.01). In OVA mice, SRT1720 treatment decreased total and eosinophil cell counts and IL‐5 and IL‐13 levels in the BAL fluid compared with the vehicle treatment (P < 0.05). In OVA mice, SRT1720 treatment also decreased inflammatory cell lung infiltrates histologically (P = 0.002). Both SRT1720 and resveratrol suppressed OVA‐induced cell proliferation and IL‐6 (P < 0.05) and tumour necrosis factor‐α (TNF‐α) (P < 0.05) production in splenocytes (P < 0.01). Conclusions: The Sirt1 activator SRT1720 suppressed inflammatory cell infiltration and cytokine production in an OVA‐induced mouse model of asthma. SRT1720 and resveratrol suppressed OVA‐induced splenocyte proliferation and TNF‐α and IL‐6 production. Sirt1 activators might have beneficial effects in asthmatics by suppressing inflammation.