OBJECTIVE — To systematically review the incidence of posttransplantation diabetes (PTD), risk factors for its development, prognostic implications, and optimal management. RESEARCH DESIGN AND METHODS — We searched databases (MEDLINE, EMBASE, the Cochrane Library, and others) from inception to September 2000, reviewed bibliographies in reports retrieved, contacted transplantation experts, and reviewed specialty journals. Two reviewers independently determined report inclusion (original studies, in all languages, of PTD in adults with no history of diabetes before transplantation), assessed study methods, and extracted data using a standardized form. Meta-regression was used to explain between-study differences in incidence. RESULTS — Nineteen studies with 3,611 patients were included. The 12-month cumulative incidence of PTD is lower (10% in most studies) than it was 3 decades ago. The type of immunosuppression explained 74% of the variability in incidence (P 0.0004). Risk factors were patient age, nonwhite ethnicity, glucocorticoid treatment for rejection, and immunosuppression with high-dose cyclosporine and tacrolimus. PTD was associated with decreased graft and patient survival in earlier studies; later studies showed improved outcomes. Randomized trials of treatment regimens have not been conducted. CONCLUSIONS — Physicians should consider modification of immunosuppressive regimens to decrease the risk of PTD in high-risk transplant recipients. Randomized trials are needed to evaluate the use of oral glucose-lowering agents in transplant recipients, paying particular attention to interactions with immunosuppressive drugs. Diabetes Care 25:583–592, 2002

A systematic review of the literature

An overview is presented of gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS), the two major hyphenated techniques employed in metabolic profiling that complement direct 'fingerprinting' methods such as atmospheric pressure ionization (API) quadrupole time-of-flight MS, API Fourier transform MS, and NMR. In GC/MS, the analytes are normally derivatized prior to analysis in order to reduce their polarity and facilitate chromatographic separation. The electron ionization mass spectra obtained are reproducible and suitable for library matching, mass spectral collections being readily available. In LC/MS, derivatization and library matching are at an early stage of development and mini-reviews are provided. Chemical derivatization can dramatically increase the sensitivity and specificity of LC/MS methods for less polar compounds and provides additional structural information. The potential of derivatization for metabolic profiling in LC/MS is demonstrated by the enhanced analysis of plant extracts, including the potential to measure volatile acids such as formic acid, difficult to achieve by GC/MS. The important role of mass spectral library creation and usage in these techniques is discussed and illustrated by examples.

http://www.univie.ac.at/mosys/Teaching_Downloads_PP_MetabolomicsDepartment/halket_et_al_jxb_2005.pdf

Chemical derivatization and mass spectral libraries in metabolic profiling by GC/MS and LC/MS/MS

Studies on the applications, energetics, and mechanisms of charge-remote fragmentations are reviewed, with emphasis given to those articles published after 1992. Independent of the charge status, charge-remote fragmentations are analogous to gas-phase thermolysis. Under collisional activation and with a fixed charge, ions containing long-chain or poly-ring structures undergo charge-remote fragmentations, generating productions that are structurally informative. Interpretation of the production spectra enables one to elucidate molecular structures. Although charge-remote fragmentations have been successfully used in the structural determination of fatty acids, phospholipids, glycolipids, triacylglycerols, steroids, peptides, ceramides, and other systems, the energetics and mechanisms of these reactions are still debated because none of the existing mechanisms can explain all the experimental data.

Applications and mechanisms of charge-remote fragmentation

Peptide and protein identification by matrix-assisted laser desorption ionization (MALDI) and MALDI-post-source decay time-of-flight mass spectrometry

A method has been developed for de novo peptide sequencing using matrix-assisted laser desorption ionization mass spectrometry. This method will facilitate biological studies that require rapid determination of peptide or protein sequences, e.g., determination of posttranslational modifications, identification of active compounds isolated from combinatorial peptide libraries, and the selective identification of proteins as part of proteome studies. The method involves fast, one-step addition of a sulfonic acid group to the N terminus of tryptic peptides followed by acquisition of postsource decay (PSD) fragment ion spectra. The derivatives are designed to promote efficient charge site-initiated fragmentation of the backbone amide bonds and to selectively enhance the detection of a single fragment ion series that contains the C terminus of the molecule (y-ions). The overall method has been applied to pmol quantities of peptides. The resulting PSD fragment ion spectra often exhibit uninterrupted sequences of 20 or more amino acid residues. However, fragmentation efficiency decreases considerably at amide bonds on the C-terminal side of Pro. The spectra are simple enough that de novo sequence tagging is routine. The technique has been successfully applied to peptide mixtures, to high-mass peptides (up to 3,600 Da) and to the unambiguous identification of proteins isolated from two-dimensional gel electrophoresis. The PSD spectra of these derivatized peptides often allow far more selective protein sequence database searches than those obtained from the spectra of native peptides.

https://www.pnas.org/content/pnas/96/13/7131.full.pdf

A method for high-sensitivity peptide sequencing using postsource decay matrix-assisted laser desorption ionization mass spectrometry.

A highly activated ester containing a fixed positive charge, S-pentafluorophenyl [tris(2,4,6-trimethoxyphenyl)phosphonium]acetate bromide (TMPP-AcSC6F5 bromide), has been synthesized as a reagent for N-terminal modification of peptides Stable in aqueous acetonitrile solution during extended storage, TMPP-AcSC6F5 bromide reacts with unprotected peptides through p-(dimethylamino)pyridine (DMAP)-promoted amidation in aqueous acetonitrile (15 min, ambient temperature) to form N-TMPP-Ac derivatives of peptides These peptide derivatives are readily amenable to analysis by fast atom bombardment (FAB) and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry Greater than 90% conversion has been observed in transforming low-nanomole quantities of analyte using molar ratios of 1:5:10 (peptide/reagent/DMAP) For reactions at the picomole level a slightly modified stoichiometry, with molar ratios of 1:10:500, is employed Owing to the high reaction efficiency and the tolerance to moderate excess re

and Douglas A. Gage

Papers

A Picomole-Scale Method for Charge Derivatization of Peptides for Sequence Analysis by Mass Spectrometry