Traditionally, non-specific chemical conjugations, such as acylation of amines on lysine or alkylation of thiols on cysteines, are widely used; however, they have several shortcomings. First, the lack of site-specificity results in heterogeneous products and irreproducible processes. Second, potential modifications near the complementarity-determining region may reduce binding affinity and specificity. Conversely, site-specific methods produce well-defined and more homogenous antibody conjugates, ensuring developability and clinical applications. Moreover, several recent side-by-side comparisons of site-specific and stochastic methods have demonstrated that site-specific approaches are more likely to achieve their desired properties and functions, such as increased plasma stability, less variability in dose-dependent studies (particularly at low concentrations), enhanced binding efficiency, as well as increased tumor uptake. Herein, we review several standard and practical site-specific bioconjugation methods for native antibodies, i.e., those without recombinant engineering. First, chemo-enzymatic techniques, namely transglutaminase (TGase)-mediated transamidation of a conserved glutamine residue and glycan remodeling of a conserved asparagine N-glycan (GlyCLICK), both in the Fc region. Second, chemical approaches such as selective reduction of disulfides (ThioBridge) and N-terminal amine modifications. Furthermore, we list site-specific antibody–drug conjugates in clinical trials along with the future perspectives of these site-specific methods.

Aims Patients with type 2 diabetes mellitus (T2DM) are prone to cardiovascular disease (CVD) due to inflammation process and oxidative stress. ADMA (Asymmetric dimethylarginine) and ICAM-1 (inter-cellular adhesion molecule-1) play an important role in CVD pathogenesis. Ginger as an anti-oxidant and anti-inflammation can effect on these biomarkers. The aim of present study was to characterize the effect of ginger supplementation on ADMA and ICAM-1 serum levels in patients with T2DM. Methods The present study is a randomized double-blind clinical trial which is conducted among 45 diabetic patients (nginger=23, nplacebo=22). The participants were randomly divided into two intervention and placebo groups which were received 2 g ginger powder and 2 g wheat flour for 10 weeks, respectively. ADMA and ICAM-1 concentration were measured by ELISA method. Results Ginger supplementation decreased ADMA serum levels significantly (P=0.002) and sICAM-1 serum levels marginally (P=0.097) in supplementation group after intervention. No significant difference was observed between placebo and supplementation groups. Conclusions Present study was conducted among patients with type 2 diabetes mellitus to investigate the effect of ginger supplementation on ADMA and sICAM-1 levels. There was a significant decrement in ADMA serum concentration and slight reduction in sICAM-1 levels in intervention group. The amount of reduction in both biomarkers was not statistically significant in between-groups comparison.

No abstract

Background:The current trend of heart transplantation in recent years has taken a quantum leap forward. We decided to look back at our experience in this center.Objectives:Here, we focus on the diagnostic pitfalls and challenges in these biopsies.Patients and Methods:Forty two patients based on the standard protocol of heart transplantation group, yielded 63 biopsy samples over a period of 33 months (April 2010 - December 2012). The mean age was 30.4 years (ranging from 16 to 58 years) with 51 males (81%) and 12 females (19%). All the patients were examined periodically and biopsy samples were taken from the right ventricular wall.Results:Rarely fewer than three pieces of myocardial samples were procured. Scar, adipose tissues and blood clots may be seen instead. Quilty effect (nodular endocardial lesions composed of inflammatory cell infiltrates) was seen in 8 cases (12.7%). Other findings not directly related to rejection including early ischemic injury, Quilty effect and post-transplant lymphoproliferative disorders (PTLD) were not encountered.Conclusions:Specimen inadequacy was not a major problem in our center. It poses a great limitation, because suboptimal specimens sometimes mislead the pathologist. Other findings especially Quilty effect were within the range defined for this finding.

No abstract