Anandamide produced by Ca2+-insensitive enzymes induces excitation in primary sensory neurons

The endogenous lipid agent N-arachidonoylethanolamine (anandamide), among other effects, has been shown to be involved in nociceptive processing both in the central and peripheral nervous systems. Anandamide is thought to be synthesised by several enzymatic pathways both in a Ca²⁺-sensitive and Ca²⁺-insensitive manner, and rat primary sensory neurons produce anandamide. Here, we show for the first time, that cultured rat primary sensory neurons express at least four of the five known Ca²⁺-insensitive enzymes implicated in the synthesis of anandamide, and that application of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-arachidonoyl, the common substrate of the anandamide-synthesising pathways, results in anandamide production which is not changed by the removal of extracellular Ca²⁺. We also show that anandamide, which has been synthesised in primary sensory neurons following the application of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-arachidonoyl induces a transient receptor potential vanilloid type 1 ion channel-mediated excitatory effect that is not inhibited by concomitant activation of the cannabinoid type 1 receptor. Finally, we show that sub-populations of transient receptor potential vanilloid type 1 ion channel-expressing primary sensory neurons also express some of the putative Ca²⁺-insensitive anandamide-synthesising enzymes. Together, these findings indicate that anandamide synthesised by primary sensory neuron via a Ca²⁺-insensitive manner has an excitatory rather than an inhibitory role in primary sensory neurons and that excitation is mediated predominantly through autocrine signalling. Regulation of the activity of the Ca²⁺-insensitive anandamide-synthesising enzymes in these neurons may be capable of regulating the activity of these cells, with potential relevance to controlling nociceptive processing.     

The HLA 8.1 ancestral haplotype is strongly linked to the C allele of -429T>C promoter polymorphism of receptor of the advanced glycation endproduct (RAGE) gene. Haplotype-independent association of the -429C allele with high hemoglobinA1C levels in diabetic patients

Previously we reported on strong linkage disequilibrium (LD) between the mono-S-C4B-RCCX module (mono-S) and the TNF2 allele (both known constituents of the 8.1 ancestral haplotype (8.1 AH)) in two Caucasian populations. The gene for the receptor of advanced glycation endproducts (RAGE) is encoded between the RCCX module and the HLA class II genes in the central MHC region. In order to assess the relationship between the promoter polymorphisms of the RAGE gene and the 8.1 AH, we performed a family study in eight informative families affected with type 1 diabetes mellitus; haplotypes of a RAGE promoter SNP (-429T>C) with the HLA-DQ2, -DR-3(17) and TNF2 alleles, as well as the mono-S genotype were determined. A similar analysis was performed in 82 unrelated patients with type 1 diabetes mellitus, and in unrelated healthy individuals of three different Caucasian populations (Hungarians, Ohioian females, Icelandics). In the diabetic patients clinical correlations were also investigated. Out of the 32 paternal and maternal chromosome 6 from the eight families, 15 different MHC haplotypes were found. Haplotypes containing at least three of the known constituents of the 8.1 AH (HLA-DQ2, -DR17, mono-S, TNF2) were always linked to the RAGE -429C allele. The RAGE -429C allele exhibited highly significant (p<0.0001) LD coefficients to known constituents of the 8.1 AH both in healthy persons and patients with type 1 diabetes. In the group of patients with diabetes we found significantly (p=0.013) higher maximal hemoglobinA1C concentration in the carriers of the RAGE -429C allele, this trait, however was not linked to the 8.1 AH. Our present findings indicate that the RAGE -429C allele can be considered as a candidate member of the 8.1 AH. The results also reveal a spectrum of recombinant MHC haplotypes in addition to the conserved ancestral haplotypes.     

Fluoroless radiofrequency and cryo-ablation of atrioventricular nodal reentry tachycardia in adults and children: a single-center experience

Background

Radiofrequency ablation (RFA) and cryo-ablation (CRA) have been traditionally performed with fluoroscopy which exposes patients and medical staff to the potential harmful effects of the X-ray. Therefore, we aimed to assess the feasibility, safety, and effectiveness of RFA and CRA of atrioventricular nodal reentry tachycardia (AVNRT) guided by the three-dimensional (3D) electro-anatomical mapping (EAM) system without the use of fluoroscopy.

Methods

We analyzed 168 consecutive patients with AVNRT, 62 of whom were under 19 years of age (128 in RFA (age 34.04 ± 21.0 years) and 40 in CRA (age 39.41 ± 22.8 years)). All procedures were performed completely without the use of the fluoroscopy and with the 3D EAM system.

Results

The acute success rates (ASR) of the two ablation methods were very high and similar (for RFA 126/128 (98.4%) and for CRA 40/40 (100%); p?=?0.43). Total procedural time (TPT) was similar in RFA and CRA groups (75.04 ± 42.31 min and 73.12 ± 30.54 min, respectively; p?=?0.79). Recurrence rates (1 (2.5%) and 8 (6.25%); p?=?0.35) were similar. There were no complications associated with procedures in either group. In pediatric group, ASR (61/62 (98.38%) and 105/106 (99.05%), respectively; p?=?0.69) and TPT (75.16 ± 42.2 min and 74.23 ± 38.3 min, respectively; p?=?0.88) were similar to the adult group. High ASR was observed with both ablation methods (for RFA 49/50, 98%, and for CRA 12/12, 100%; p?=?0.62] with very high arrhythmia-free survival rates (for RFA 98% and for CRA 100%; p =?0.62).

Conclusion

Based on these results, it can be suggested that fluoroless RFA or CRA guided by the 3D EAM system can be routinely performed in all patients with AVNRT without compromising safety, efficacy, or duration of the procedure.

     

Laparoscopic unroofing of retroperitoneal lymphoceles after bilateral retroperitoneal lymphadenectomy for testicular cancer

Telesurgery is a form of operative videoconferencing in which a remotely located surgeon observes a procedure through a camera and provides visual and auditory feedback to the operative site. With the use of more robotic devices in laparoscopic surgery, various forms of telesurgery have been tried. We describe the first two international telesurgical, telementored, robot-assisted laparoscopic cholecystectomies performed in the world, between the Johns Hopkins Institute, Baltimore, Maryland, USA, and the National University Hospital, Singapore.     

Fluoroless catheter ablation of various right and left sided supra-ventricular tachycardias in children and adolescents

Electrophysiology study (EPS) and catheter ablation (CA) in children and adolescents carries a potentially harmful effect of radiation exposure when performed with the use of fluoroscopy. Our aim was to evaluate the feasibility, safety and effectiveness of fluoroless EPS and CA of various supra-ventricular tachycardias (SVTs) with the use of the 3D mapping system and intracardiac echocardiography (ICE). Forty-three consecutive children and adolescents (age 13?±?3 years) underwent fluoroless EPS and CA for various supra-ventricular tachycardias. A three-dimensional (3D) mapping system NavX? was used for guidance of diagnostic and ablation catheters in the heart. ICE was used as a fundamental imaging tool for transseptal punctures. Acute procedural success rate was 100?%. There were no procedure related complications and short-term follow up (10?±?3 months) revealed 93?% arrhythmia free survival rate. Fluoroless CA of various SVTs in the paediatric population is feasible, safe and can be performed successfully with 3D mapping system and ICE.