Lability of N-alkylated peptides towards TFA cleavage

Trifluoroacetic acid (TFA) is a common reagent in both solid-phase and solution peptide synthesis. It is used for the deprotection and/or cleavage of the synthesized peptide from the resin. The use of TFA under these standardized conditions is thought to be sufficiently mild, thereby preventing degradation of the desired product. However, peptides of the general structure R¹-(N-alkyl X₁)-X₂-R² are hydrolyzed by standard TFA solid-phase peptide synthesis (SPPS) cleavage/deprotection conditions providing fragments R¹-(N-alkyl X₁)-OH and H-X₂-R². The fragmentation is observed during a TFA cleavage both from the resin and in solution. The hydrolysis is proposed to proceed via an oxazolone-like intermediate in which equilibration of the chiral center of the N-alkylated residue occurs. This mechanism is supported by H/D exchange as observed by MS and NMR in conjunction with HPLC. © Munksgaard 1996.     

Effect of Distance on the Power Density from Two Light Guides

Purpose: This study determined the effect of distance on the power density from standard and Turbo light guides (Demetron/Kerr, Danbury, Connecticut). Materials and Methods: Power density was measured from 0 to 10 mm away from the tip of standard 8‐mm curved light guides and 13/8‐mm Turbo curved light guides. To determine the effect of distance on power density, a polynomial regression line was fitted. The Kolmogorov‐Smirnov (K‐S) statistic and the Wilcoxon rank sum (WR) tests were used to determine if there was a difference in the rate at which the power density decreased for the standard and Turbo light guides as the distance from the tip increased. Photographs of the light dispersion from each tip were also taken. Results: At 0 mm, the mean (± SD) power density from the two standard light guides was 743 ± 6.1 mW/cm² and from the four Turbo light guides was 1128 ± 22.1 mW/cm². As the distance from the tip of the light‐guide tip increased, the power density decreased, but the rate of decrease was greater from the Turbo light guides than from the standard light guides. At 6 mm the power density from the standard light guides fell to 372 mW/cm² (50% of the original value) and the power density from the Turbo light guides fell to 263 mW/cm² (23% of the original value). Both the K‐S statistic and the WR sum test indicated that the distribution of light intensities was significantly different from the two light guides (WR p‐value = .0246, K‐S p‐value < .0001). The two estimated polynomials intersected at 3.66 mm, and the 95% prediction intervals intersected at about 2.8 and 4.8 mm. Therefore, beyond 5 mm away from the tip of the light guide, the standard light guides gave higher power density readings than the Turbo light guides. Photographs showed that the light dispersed at a wider angle from the Turbo light guides than from the standard light guide. CLINICAL SIGNIFICANCE The design of the light guide of a light curing unit affects light dispersion, power density, and ultimately the dentist's ability to properly cure composite. For these reasons, manufacturers should report the power density at the tip of the light guide and 6 mm from the tip of the light guide, since significant differences exist between light guide designs.     

FIBRIN CUFF LYSIS IN CHRONIC VENOUS ULCERS TREATED WITH A HYDROCOLLOID DRESSING

Background. Pericapillary fibrin cuffs (PFC) are a recognized part of the pathology of venous stasis ulcers. A hydrocolloid dressing capable of lysing wound surface fibrin was tested in venous ulcers for its capacity to lyse pericapillary fibrin below the wound surface. Methods. Tissue biopsies from the rims of 19 venous ulcers were evaluated for thickness of shallow and deep dermal PFCS before and after treatment with DuoDERM covered by Unna's boot and a compression bandage (DD+UB; n=9) versus the same treatment without the hydrocolloid dressing (UB; n=10). Frozen sections of all biopsies were stained with an immunofluorescent antibody to fibrin for rating of PFC thickness. Separate sections were stained with hematoxylin and eosin to assess capillary frequency, histopathology, and inflammation. All ratings and pathology assessments were performed blinded to treatment conditions. Results. Both deep and shallow PFCS were reduced in 89% of ulcers treated with DD+UB versus 40% of ulcers treated with UB (α < 0.04). No other significant differences in inflammation, histopathology, or capillary frequency were observed. Conclusions. Treatment with DD+UB reduced PFCS in twice the number of ulcers than UB alone in 1 week. This is the first scientific documentation that a topical wound dressing could reduce the pathophysiology associated with venous ulcers, beyond the known beneficial effect of graduated compression. Not all hydrocolloid dressings are fibrinolytic, so this effect may not generalize to other dressings.     

Colonic Perforation Following Intraoperative Temporary Pacemaker Implantation

OZA, P.M., et al .: Colonic Perforation Following Intraoperative Temporary Pacemaker Implantation. This report describes the case of a 73-year-old man who was referred for consultation for increasing abdominal free air 1 week after he underwent surgery for aortic valve replacement and coronary artery bypass grafting with intraoperative pacemaker implantation. Laparoscopic exploration revealed that the pacemaker wires had passed through the left transverse colon. Although no previous reports of colonic perforation due to pacemaker lead placement was found, this experience suggests that physicians should suspect this complication in patients with increasing free intraabdominal air and peritoneal signs who have recently undergone placement of a temporary cardiac pacing system. (PACE 2003; 26[Pt. I]:918–919)     

Antibodies to Plasmodium falciparum gamete surface antigens in Papua New Guinea sera

Sera from individuals living in malaria endemic areas of Papua New Guinea were tested for their effect on infectivity of Plasmodium falciparum gametocytes grown in culture to Anopheles freeborni mosquitoes. Consistent reduction of infectivity to less than 5% of control was observed with nine out of the 41 sera from the endemic area tested and also with three out of seven sera tested from individuals rarely exposed to malaria infection. Gamete surface antigens recognized by the sera were investigated by immunoprecipitation from 125I surface-labelled gametes extracted in SDS and Triton X-100. The main antigens recognized were of the same mol. wt (230, 48 and 45 kD) as those known to be targets of transmission-blocking monoclonal antibodies. A significant negative correlation was observed between the total ct/min immunoprecipitated from surface-labelled gametes by the sera and the average number of oocysts per gut observed in membrane feeding experiments with these sera. Spearmann's rank correlation coefficient indicated that suppression of infectivity correlated strongly with the presence of antibodies against the 230 kD protein; there was no significant correlation between suppression and antibodies to the 48/45 kD proteins. The antibody response to the different gamete surface antigens varied greatly in sera from the endemic areas suggesting that individuals respond differently to each gamete antigen.     

Efficacy of a nicotine nasal spray in smoking cessation: a placebo-controlled, double-blind trial

Laboratory trials have demonstrated the efficacy of nicotine replacement in smoking cessation bur absolute success races are low. For many, nicotine gum is hard to use and transdermal nicotine is slow-acting and passive. A new, faster-acting nicotine nasal spray (NNS) can provide easily self-administered relief from cigarette withdrawal. The NNS was tested for safely and efficacy in smoking cessation. Two hundred and fifty-five smokers were randomized to NNS or a piperine placebo. Drug use was limited to 8–32 doses/day for 6 months. Subjects were tested while smoking and at post-cessation daily (week 1) with follow-up at weeks 2, 3, 6 and at 3 months, 6 months and 1 year. Continuous abstinence analyses (CO ≤8 ppm.; no slips) showed that NNS significantly enhanced success rates over placebo overall (p < 0.001) and at all test intervals. Differences at key intervals between active and placebo were: 63% vs. 40% (day 5), 51% vs. 30% (week 3), 43% vs. 20% (6 weeks), 34% vs. 13% (3 months), 25% vs. 10% (6 months) and 18% vs. 8% (1 year). Side effects were common but tolerable. Cotinine measures showed that replacement of nicotine approximated 30% of smoking levels. Hazard functions revealed relapse risks peaked at day 1, day 5 and 3 weeks for strict abstinence. It is concluded NNS is safe, efficacious and a viable alternative treatment for smoking cessation.     

Bradycardia and Syncope in Children Not Controlled by Pacing: Beta-Adrenergic Hypersensitivity

Cardiac pacing is frequently employed in the therapy of children with syncope and documented bradycardia. This report describes two children, ages 7 and 9 years, who underwent placement of demand ventricular pacing systems for documented bradycardia and syncope. Cardiac catheterization and intracardiac electrophysiological studies failed to show evidence of structural abnormalities, sinus node or conduction system disease, inducible arrhythmias, or VA conduction in each patient. Both patients had persistent symptoms after pacemaker implantation. Autonomic function testing with continuous heart rate and blood pressure monitoring revealed exaggerated beta-adrenergic responses to simple standing and small doses of isoproterenol. Symptoms were completely eliminated with atenolol. In these two children, cardiac pacing alone was not adequate for relief of symptoms. Autonomic mechanisms of bradycardia and hypotension should be considered prior to implantation of permanent pacing systems in children.