Radioiodination and bioevaluation of rolipram as a tracer for brain imaging: In silico study,molecular modeling and gamma scintigraphy

Brain imaging is considered one of the most fruitful applications of radioisotope scanning. Rolipram, a selective phospodiesterase‐4 inhibitor, has been labeled using [¹²⁵I] with chloramine‐T (Ch‐T) as an oxidizing agent. Factors, such as the amount of substrate, pH, the amount of oxidizing agent, temperature, and the reaction time, have been systematically studied to optimize the iodination process. In addition, bio‐distribution studies have indicated that the brain uptake of [¹²⁵I]iodorolipram is 7.6 ± 0.33 injected dose/g organ at 10 minutes post‐injection, which cleared from the brain with time until it reaches 1.30 ± 0.17% at 1 hour post‐injection. Therefore, iodorolipram could be considered as a potential, new selective radiotracer for brain imaging.     

Ridge preservation and augmentation using regenerative materials to enhance implant predictability and esthetics

Dentistry has entered an era in which patients no longer need to accept an edentulous or partially edentulous condition, or one in which their candidacy for tooth structure replacement (ie, implants with subsequent restoration) must be dismissed because of insufficient alveolar bone volume, height, or width. The supporting bone can be preserved at the time of tooth extraction, or augmented at the time of case presentation, using a variety of available regenerative materials. Among them are mineralized human allograft bone and collagen membranes that can be placed in combination with specific growth factor complexes and implant designs. This article reviews the challenges associated with adequately preserving or augmenting the alveolar bone after tooth extraction or loss and before implant placement. The research and benefits to support using allogenic bone graft and membrane materials for such procedures are detailed, and 3 clinical cases are presented to demonstrate the clinically successful incorporation of these materials with the host tissues.     

Quantitative and qualitative changes in anti-Neu5Gc antibody response following rabbit anti-thymocyte IgG induction in kidney allograft recipients

Antibodies of non-human mammals are glycosylated with carbohydrate antigens, such as galactose-α-1-3-galactose (α-Gal) and N-glycolylneuraminic acid (Neu5Gc). These non-human carbohydrate antigens are highly immunogenic in humans due to loss-of-function mutations of the key genes involved in their synthesis. Such immunogenic carbohydrates are expressed on therapeutic polyclonal rabbit anti-human T-cell IgGs (anti-thymocyte globulin; ATG), the most popular induction treatment in allograft recipients. To decipher the quantitative and qualitative response against these antigens in immunosuppressed patients, particularly against Neu5Gc, which may induce endothelial inflammation in both the graft and the host. We report a prospective study of the antibody response against α-Gal and Neu5Gc-containing glycans following rabbit ATG induction compared to controls. We show a drop in the overall levels of anti-Neu5Gc antibodies at 6 and 12 months post-graft compared to the pre-existing levels due to the major early immunosuppression. However, in contrast, in a cross-sectional study there was a highly significant increase in anti-Neu5Gc IgGs levels at 6 months post-graft in the ATG-treated compared to non-treated patients(P = 0.007), with a clear hierarchy favouring anti-Neu5Gc over anti-Gal response. A sialoglycan microarray analysis revealed that the increased anti-Neu5Gc IgG response was still highly diverse against multiple different Neu5Gc-containing glycans. Furthermore, some of the ATG-treated patients developed a shift in their anti-Neu5Gc IgG repertoire compared with the baseline, recognizing different patterns of Neu5Gc-glycans. In contrast to Gal, Neu5Gc epitopes remain antigenic in severely immunosuppressed patients, who also develop an anti-Neu5Gc repertoire shift. The clinical implications of these observations are discussed.     

Five-year follow-up after percutaneous balloon mitral valvuloplasty in children and adolescents

Balloon mitral valvuloplasty (BMV) is an effective intervention in patients with symptomatic mitral stenosis. However, the late results of BMV in children and adolescents have not been well studied. The aim of this study was to assess the late functional and morphologic results after BMV in children and adolescents. BMV was performed in 46 children and adolescents (mean age 15.5 +/- 3.2 years, range 7 to 19; 19 males) with rheumatic mitral stenosis. Serial clinical and echocardiographic evaluation was conducted to assess the long-term results of the procedure during a follow-up period of 66 +/- 6 months. The mitral valve score was 6 +/- 2/16. BMV was successful in 45 patients (98%). There was a significant increase of the mean mitral valve area index (MVAI) (0.65 +/- 0.14 vs 1.54 +/- 0.23 cm2/m2, p <0.001) and a significant reduction of the mean transmitral pressure gradient (16.1 +/- 2.9 vs 5.1 +/- 3.1 mm Hg, p <0.001) from pre- to post-BMV, respectively. There was no significant change of MVAI or the pressure gradient during the follow-up compared with immediately after BMV (1.51 +/- 0.31 cm2/m2 and 4.9 +/- 2.5 mm Hg, respectively). No deaths or mitral valve replacement occurred during the follow-up period. Restenosis (loss of >50% of the achieved increase in MVAI) occurred in 3 patients (6.5%). All other patients showed persistent improvement in their New York Heart Association class (< or = II). Thus, the event-free survival with good functional results was encountered in 42 patients (91%) at the end of the follow-up period. The left atrial diameter decreased from 4.6 +/- 0.9 before BMV to 3.7 +/- 0.6 cm at follow-up (p <0.05). It is concluded that BMV has excellent intermediate-term results in children and adolescents with a relatively low mitral valve score.     

Mechanism of antithrombin III inhibition of factor VIIa/tissue factor activity on cell surfaces. Comparison with tissue factor pathway inhibitor/factor Xa-induced inhibition of factor VIIa/tissue factor activity

Recent studies have shown that antithrombin III (AT III)/heparin is capable of inhibiting the catalytic activity of factor VIIa bound either to relipidated tissue factor (TF) in suspension or to TF expressed on cell surfaces. We report studies of the mechanism of which by AT III inhibits factor VIIa bound to cell surface TF and compare this inhibitory mechanism with that of tissue factor pathway inhibitor (TFPI)-induced inhibition of factor VIIa/TF. AT III alone and AT III/heparin to a greater extent reduced factor VIIa bound to cell surface TF. Our data show that the decrease in the amount of factor VIIa associated with cell surface TF in the presence of AT III was the result of (1) accelerated dissociation of factor VIIa from cell surface TF after the binding of AT III to factor VIIa/TF complexes and (2) the inability of the resultant free factor VIIa-AT III complexes to bind effectively to a new cell surface TF site. Binding of TFPI/factor Xa to cell surface factor VIIa/TF complexes markedly decreased the dissociation of factor VIIa from the resultant quaternary complex of factor VIIa/TF/TFPI/factor Xa. Addition of high concentrations of factor VIIa could reverse the AT III-induced inhibition of cell surface factor VIIa/TF activity but not TFPI/factor Xa-induced inhibition of factor VIIa/TF activity.     

Side-to-side nerve bridges reduce muscle atrophy after peripheral nerve injury in a rodent model

Background

Peripheral nerve injury can result in muscle atrophy and long-term disability. We hypothesize that creating a side-to-side bridge to link an injured nerve with a healthy nerve will reduce muscle atrophy and improve muscle function.

Methods

Sprague-Dawley rats were divided into four groups (n = 7 per group). Group 1: transection only—a 10-mm gap was created in the proximal tibial nerve; group 2: transected plus repaired—the transected tibial nerve was repaired; group 3: transected plus repaired plus nerve bridge—transected nerve repaired with a distal nerve bridge between the tibial and peroneal nerves via epineurial windows; and group 4: transected plus nerve bridge—transected tibial nerve left unrepaired and distal bridge added. Gait was assessed every 2 wk. At 90 d the following measures were determined: gastrocnemius mass, muscle and nerve nuclear density, and axonal infiltration into the nerve bridge.

Results

Groups 3 and 4 had greater improvements in walking track recovery than groups 1 and 2. Group 3's gastrocnemius muscles exhibited the least amount of atrophy. Groups 1, 2, and 4 exhibited greater histologic appearance of muscle breakdown compared with group 3 and control muscle. Finally, most bridges in groups 3 and 4 had neuronal sprouting via the epineurial windows.

Conclusions

Our study demonstrated reduced muscle atrophy with a side-to-side nerve bridge in the setting of peripheral nerve injury. These results support the application of novel side-to-side bridges in combination with traditional end-to-end neurorrhaphy to preserve muscle viability after peripheral nerve injuries.