The effect of periodontitis on recipient outcomes after kidney transplantation

Background Recent several reports have demonstrated that periodontitis is prevalent and adversely affects the survival in patients with chronic kidney disease (CKD) or end-stage kidney disease. However, its impact on transplant outcomes remains uncertain. Methods This retrospective cohort study included 136 and 167 patients, respectively, who underwent living donor kidney transplantation (KT) at Seoul National University Hospital from July 2012 to August 2016 and Korea University Hospital from April 2008 to October 2018. We divided patients into three groups according to stages of periodontitis based on a new classification system. Results Patients with severe periodontitis were older, had a higher prevalence of diabetes, a higher body mass index and C-reactive protein level, a lower cardiac output, and were more likely to be smokers, indicating its association with chronic systemic inflammation. After KT, stage IV periodontitis was independently associated with a lower incidence of acute T cell-mediated rejection, suggesting the possible effect of periodontitis on immune function. However, 1-year and 3-year estimated glomerular filtration rates were not different. Among the KT recipients followed up more than 3 years, new-onset cardiovascular disease occurred in nine patients, and coronary artery disease occurred more frequently in patients with stage IV periodontitis. However, diabetes was the independent predictor of new-onset coronary artery disease in multivariate logistic regression analysis. Conclusion Our findings showed that periodontitis might be an important player in determining posttransplant outcomes in recipients. Further interventional trials to test whether treating periodontitis could modify transplant outcome are needed

Failure of a Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy of H. pylori Eradication in H. pylori-Infected Patients with Functional Dyspepsia

BACKGROUND/AIMS: The role of Helicobacter pylori eradication in patients with functional dyspepsia (FD) is still uncertain. We originally planned a randomized clinical study to observe dyspeptic symptoms after H. pylori eradication therapy. However, we failed to complete the study; therefore, we analyzed the factors that affected the failure of the study. METHODS: Interviews and questionnaire surveys were conducted to analyze the factors that induced early termination from the study. RESULTS: Many patients were screened by gastroenterologists at 11 tertiary referral hospitals between July 2009 and August 2010; however, only 4 patients met the enrollment criteria. Most patients who visited our clinics had been experiencing FD symptoms for less than 6 months or were already taking medication. They also demanded to continue taking medications and using other drugs. Only 3 of the 4 patients signed informed consent. CONCLUSIONS: The application of the current Rome III criteria to FD is difficult to evaluate in Korean patients with dyspeptic symptoms because of the early medical evaluation. Most Korean patients who were diagnosed with FD by the Rome III criteria did not overcome their fear of being unable to use rescue medications during the study period.ope

Structure and Dynamics of Theophylline in D2O Investigated by 2D IR

Theophylline is one of the xanthine derivatives. The molecular structure of theophylline is like purine (i.e., adenine and guanine), so it acts like a competitive and nonspecific ribonucleoside inhibitor. Because of this character, theophylline has been widely used as tablet pills to help asthma patients. The crystal structure of theophylline monohydride and the intermolecular interaction between theophylline and DNA/RNA sequences has been reported to improve its pharmaceutical usage. We investigated the structure and dynamics of theophylline using Fourier transform infrared (FT IR) and two-dimensional infrared (2D IR) spectroscopy to understand molecular couplings and vibrational dynamics of two carbonyl groups, which have not been studied so far. We obtained time-resolved 2D IR spectra of theophylline in D2O solution from T = 0 to T = 10 ps, with four different polarization sets. We observed cross peaks between the two C=O modes of theophylline in the 2D IR spectra, where the magnitude and sign of the cross peaks depend on the polarization of the involved IR pulses. The two modes were determined to be almost orthogonal to each other due to strong coupling. Time-dependent 2D IR spectra revealed energy transfer between the two modes and H-bond exchange between the C=O and water occurring predominantly in one of the C=O groups

Direct Evidence of Channel-Water Dynamics Related with the Structure Changes in a Transmembrane Ion Channel

Knowledge of both structural and dynamical characteristics are essential to understand the function of membrane proteins. Two-dimensional infrared (2D IR) spectroscopy can detect small changes in secondary structure as well as measure fast structure dynamics on the picosecond timescale. Here, we report a 2D IR spectroscopic investigation to probe the backbone configurations of the transmembrane domain of M2 proton channel in a solid-supported membrane environment. Our results show that a helix kink at higher pH (7.5) occludes the passage of water molecules into the channel, making the channel inactive. A conformational change upon lowering the pH (5.5), shows ultrafast hydrogen-bond dynamics between the amide carbonyls of the transmembrane protein and the water molecules, confirming the presence of water inside the channel in the active state. This result suggests that the rate of proton diffusion is closely related to the water dynamics induced by the structural change in the protein

Interpretation of Hofmeister series: Formation of an amide tautomer by divalent cations

Ion-specific effects on peptides and proteins are crucial to the biomolecular structure. Compared with the significant role of anions, the subtle effects of cations on proteins have not been clearly understood. Importantly, divalent cations like Ca2+ and Mg2+ are known to be crucial to biological functions. Herein, we report that the direct binding of the divalent cations to the amide oxygen in aqueous solution triggers an amide???iminolate tautomer equilibrium. For N-methyl acetamaide (NMA) dissolved in aqueous 5M CaCl2 solution, the formation of an amide tautomer is strongly supported by two-dimensional infrared (2D IR) spectroscopy of the amide vibration and molecular dynamics (MD) simulations of molecular phenomenon. The interconversion timescale (~17 ps) between the tautomers confirms that Ca2+ forms direct contact with the amide O intermittently. These results confirm the arrest of an unusual amide tautomer by the divalent cations and provide an explanation for the shift in the aggregation pathway of neurotoxic peptides in the presence of divalent cations

2D IR Study of the Aggregation Pathway of hIAPP oligomers

Type 2 diabetes (T2D) is a disease in which human islet amyloid polypeptide (hIAPP) amyloid deposits attack ??-cells, causing insulin production problems and the loss of blood sugar control. Although the formation process of hIAPP deposits has been studied for several decades, the early stage of the aggregation mechanism is not fully understood due to the transient nature of intermediate oligomers. In this regard, we slowed down the aggregation process by lowering the sample temperature and observed the aggregation process in detail. The aggregation process was clearly observed by 2D IR to be reversible at the early stage aggregation