Cyclization of disulfide-containing peptides in solid-phase synthesis†

Disulfide-containing peptides may be obtained in good yields and purities when oxidations are carried out on peptide chains anchored to polymeric supports used for solid-phase synthesis. Such approaches take advantage of the pseudo-dilution phenomenon which favors intramolecular processes. A variety of procedures have been demonstrated using the related model peptides Ac-Cys-Pro-d Val-Cys-NH₂ and Ac-Pen-Pro-d Val-Cys-NH₂ (which both readily assume a type II β-turn conformation that becomes stabilized by a 14-membered disulfide-containing intramolecular ring), and oxytocin (conformationally mobile 20-membered disulfide ring). Both Boc and Fmoc were used for Nα-amino protection, the β-thiols of cysteine or penicillamine were blocked by S-acetamidomethyl (Acm), S-9-fluorenylmethyl (Fm), or S-trityl (Trt), and compatible anchoring linkages included HF-labile 4-methylbenzhydrylamide (MBHA), TFA-labile tris (alkoxy)benzylamide (PAL), and photolabile o-nitrobenzylamide (Nonb). Assemblies of linear sequences proceeded smoothly, and polymer-supported oxidations were carried out in a variety of ways either directly or after deblocking to the resin-bound dithiol. Chains were released from the support without substantial damage to the disulfide bridges, and overall yields were as high as 60-90%.     

Prison Based Occupational Therapy

Occupational therapy within a prison environment is a comparatively new area of practice. This paper draws on the experience of occupational therapists who have worked in “G” Division, Pentridge Prison, the only psychiatric facility of the Victorian penal system. It outlines the philosophical model used for their intervention and gives an example of its practical application. The authors hope that, through this paper, they will demystify some of the myths related to working in prisons, so as to encourage further participation of occupational therapists in this specialist field.     

Bullous pemphigoid occurring in psoriatic plaques in association with Hashimoto''s thyroiditis

We describe a patient with psoriasis who developed bullous pemphigoid in sites of psoriatic plaques, in whom there was a second organ-specific auto-immune disorder, Hashimoto's thyroiditis.     

Radiofrequency Modification of the Atrioventricular Node in Patients with Chronic Atrial Fibrillation:

RF Modification of AVN in AF. Introduction : We compared, in a prospective and randomized fashion with a cross-over design, the anterior and posterior approaches to radiofrequency (RF) modification of the AV node in patients with chronic atrial fibrillation.
Methods and Results : Thirty-three patients were randomized to receive first an anterior (group I) or posterior (group II) approach for RF modification of AV nodal conduction. Patients who did not fill the endpoint ventricular rate (< 90 beats/min) were crossed over to the alternative approach. After the anterior approach in group I patients, mean ventricular rate was significantly lower than in group II patients after the posterior approach (79.6 ± 18.8 beats/min vs 110.8 ± 16.2 beats/min, P < 0.001). In group I, 14 (82%) of 17 patients fulfilled the endpoint, 1 (6%) had complete AV block, and 2 (12%) were crossed over to the posterior approach fulfilling the endpoint. In group II, 4 (25%) of 16 patients fulfilled the endpoint. No transient or permanent high-degree AV block was observed. Among the 12 patients who were crossed over to the anterior approach, 8 fulfilled the endpoint, whereas 4 had permanent high-degree AV block. RF ablation carried out only in the anterior region was safer than a stepwise approach (6% vs 33% incidence of AV block), even though the difference did not reach statistical significance (P = 0.09).
Conclusion : Posterior AV nodal modification is less effective but safer than anterior AV nodal modification. However, to reduce the incidence of AV block, the anterior approach is preferable to a stepwise approach from the posterior to the anterior zone.     

Six-month Follow-up of Successful Stenting for Acute Dissection After Coronary Angioplasty: Comparison Between Slotted Tube (Palmaz-Schatz) and Flexible Coil (Gianturco-Roubin) Stent Designs

The aim of this study was to evaluate the influence that two different stent designs may have in late outcome following successful coronary stent implantation for acute dissection after balloon angioplasty. In the present study, 50 consecutive patients were matched to compare late outcome between the use of slotted tube (Palmaz-Schatz) and flexible coil (Gianturco-Roubin) stent designs (25 in each group). Group matching was performed according to vessel size, location of target lesion, and dissection type among patients undergoing successful coronary stenting to treat an acute dissection following balloon coronary angioplasty. Poststent minimal luminal diameter (2.46 ± 0.49 mm vs 2.35 ± 0.47 mm, not significant [NS]) and acute luminal gain (2.02 ± 0.61 mm vs 1.85 ± 0.56 mm, NS) were similar in slotted tube and flexible coil stent groups, respectively. However, at 6-month follow-up, late loss in luminal diameter was larger in lesions treated with a flexible coil stent (0.96 ± 0.75 mm vs 0.62 ± 0.55 mm, P = 0.05), and minimal luminal diameter was smaller in those lesions treated with a flexible coil stent (1.38 ± 0.87 mm vs 1.84 ± 0.63 mm, P < 0.05). Angiographic restenosis (> 50% diameter narrowing) occured in four lesions treated with a slotted tube stent (16%) compared to ten lesions treated with a flexible coil stent (40%, P < 0.05). The design of the coronary stent may have significant influence in the late lesion outcome. In patients with acute dissection following balloon coronary angioplasty, use of a slotted tube stent design (Palmaz-Schatz) may result in lower late loss and larger luminal diameter at 6-month follow-up than use of a flexible coil stent design (Gianturco-Roubin).