How to rescue high-dose methotrexate induced nephrotoxicity and literature review about hemodiafiltration?

Methotrexate (MTX) is a highly renal and liver toxicity drug used in hematological malignancy treatment in children and adults. High-dose methotrexate (HD-MTX) therapy may cause impairment of kidney and decrease the elimination of MTX, at the same time, the serum concentration of MTX increased. Today the treatment for preventing MTX toxicity after renal shutdown is Carboxypeptidase. We report a patient who experienced nephrotoxicity after the HD-MTX infusions during the treatment for non-Hodgkin lymphoma (NHL) and received hemodiafiltration (HDF) with large dose of leucovorin (LV) to treat MTX intoxication. LV is very potent in the prevention of neurotoxicity and administration of LV could protect the normal cells, but the dosage and duration of LV should be according to the MTX concentration. Although a large dose of LV was applied, the patient's condition did not improve. It was found that the HDF with large dose of LV to save the patient and steadily improved the patient's clinical condition.

Joint effects of mitochondrial DNA4977 deletion and serum folate deficiency on coronary artery disease in type 2 diabetes mellitus.

BACKGROUND & AIMS: The 4977-bp mitochondrial deletion (mtDNA4977 deletion), as a hallmark of mitochondrial oxidative damage, may play an important role in coronary artery disease (CAD), but its interaction with folate deficiency among diabetic patients is largely unknown. We aimed to explore the joint association of leukocyte mtDNA4977 deletion and serum folate status with obstructive CAD in Chinese adults with type 2 diabetes. METHODS: We cross-sectionally analyzed the angiographic data of 2017 diabetic patients without B-vitamin supplementation. Of the 2017 participants, 756 who received percutaneous coronary intervention (PCI) completed prospective follow-up of one year. In vitro, we explored the mediation effects of mitochondrial reactive oxygen species (mtROS) in folic acid (FA)-deficient human aortic smooth muscle cells (HASMCs) under hyperglycemic conditions. RESULTS: Cross-sectionally, the multivariate odds ratios (ORs) for obstructive CAD were 1.41 (95% CI: 1.29-1.55) for greater mtDNA4977 deletion, and 1.15 (95% CI: 1.05-1.25) for lower folate levels. Particularly, the combination of high mtDNA4977 deletion (top tertile) and folate deficiency (serum folate < 6 ng/mL) was associated with more than 2-fold increased odds of having obstructive CAD and higher degrees of coronary stenosis. Prospectively, the hazard ratio for all-cause death at 1-year after PCI was up to 2.37 (95% CI: 1.21-4.63) for folate-deficient participants in the top tertile of mtDNA4977 deletion. In HASMCs, the adverse effects of FA deficiency were aggravated by induction of mtROS, and attenuated by scavenging of mtROS. CONCLUSIONS: The risk of obstructive CAD may be greatly increased by the interaction between greater mtDNA4977 deletion and folate deficiency among diabetic patients.

Macrocycle-Directed Construction of Tetrahedral Anion-π Receptors for Nesting Anions with Complementary Geometry.

Manipulation of the emerging anion-π interactions in a highly cooperative manner through sophisticated host design represents a very challenging task. In this work, unprecedented tetrahedral anion-π receptors have been successfully constructed for complementary accommodation of tetrahedral and relevant anions. The synthesis was achieved by a macrocycle-directed approach by using large macrocycle precursors bearing four reactive sites, which enabled a kinetic-favored pathway and afforded the otherwise inaccessible tetrahedral cages in considerable yields. Crystal structure suggested that the tetrahedral cages have an enclosed three-dimensional cavity surrounded by four electron-deficient triazine faces in a tetrahedral array. The complementary accommodation of a series of tetrahedral and relevant anions including BF4 - , ClO4 - , H2 PO4 - , HSO4 - , SO4 2- and PF6 - was revealed by ESI-MS and DFT calculations. Crystal structures of ClO4 - and PF6 - complexes showed that the anion was nicely encapsulated within the tetrahedral cavity with up to quadruple cooperative anion-π interactions by an excellent shape and size match. The strong anion-π binding was further confirmed by negative ion photoelectron spectroscopy measurements.

Are carboxyl groups the most acidic sites in amino acids? Gas-phase acidities, photoelectron spectra, and computations on tyrosine, p-hydroxybenzoic acid, and their conjugate bases.

Deprotonation of tyrosine in the gas phase was found to occur preferentially at the phenolic site, and the conjugate base consists of a 70:30 mixture of phenoxide and carboxylate anions at equilibrium. This result was established by developing a chemical probe for differentiating these two isomers, and the presence of both ions was confirmed by photoelectron spectroscopy. Equilibrium acidity measurements on tyrosine indicated that deltaG(acid)(o) = 332.5 +/- 1.5 kcal mol(-1) and deltaH(acid)(o) = 340.7 +/- 1.5 kcal mol(-1). Photoelectron spectra yielded adiabatic electron detachment energies of 2.70 +/- 0.05 and 3.55 +/- 0.10 eV for the phenoxide and carboxylate anions, respectively. The H/D exchange behavior of deprotonated tyrosine was examined using three different alcohols (CF3CH2OD, C6H5CH2OD, and CH3CH2OD), and incorporation of up to three deuterium atoms was observed. Two pathways are proposed to account for these results, and all of the experimental findings are supplemented with B3LYP/aug-cc-pVDZ and G3B3 calculations. In addition, it was found that electrospray ionization of tyrosine from a 3:1 (v/v) CH3OH/H2O solution using a commercial source produces a deprotonated [M-H]- anion with the gas-phase equilibrium composition rather than the structure of the ion that exists in aqueous media. Electrospray ionization from acetonitrile, however, leads largely to the liquid-phase (carboxylate) structure. A control molecule, p-hydroxybenzoic acid, was found to behave in a similar manner. Thus, the electrospray conditions that are employed for the analysis of a compound can alter the isomeric composition of the resulting anion.

[Effect of shenkang injection on hypertrophy and expressions of p21 and p27 in glomerular mesangial cells of rats cultured in high glucose].

OBJECTIVE: To investigate the effect of Shenkang Injection (SI) on hypertrophy and expressions of p21 and p27 in glomerular mesangial cells of rats cultured in high glucose fluid. METHODS: Cultured rat glomerular mesangial cells were divided into 6 groups: the normal control group, mannitol-treated group, high glucose-treated group, high, middle and low dose SI treated groups. The synthesis of cell protein and DNA were determined with incorporation of 3H-TdR and 3H-Leu. The changes of p21 mRNA and expressions of p21 and p27 protein were determined by reverse transcriptase polymerase chain reaction and Western blot. RESULTS: High glucose caused incorporation of 3H-TdR reduced, incorporation of 3H-Leu increased. SI could decrease incorporation of 3H-Leu, increase incorporation of 3H-TdR. Compared with the high glucose-treated group, SI could inhibit the overexpression of p2l mRNA and protein,p27 protein induced by high glucose. CONCLUSION: SI could inhibit hypertrophy of glomerular mesangial cells cultured in high glucose partly through inhibiting overexpressions of p2l mRNA, p21 and p27 protein.