Conformation of Alkali Metal Ion−Benzo-12-Crown‑4 Complexes Investigated by UV Photodissociation and UV−UV Hole-Burning Spectroscopy

We measure UV photodissociation (UVPD) spectra of benzo-12-crown-4 (B12C4) complexes with alkali metal ions, M+·B12C4 (M = Li, Na, K, Rb, and Cs), in the 36300−37600 cm−1 region. Thanks to the cooling of ions to ∼10 K, all the M+·B12C4 complexes show sharp vibronic bands in this region. For UV−UV hole-burning (HB) spectroscopy, we first check if our experimental system works well by observing UV−UV HB spectra of the K+ complex with benzo-18-crown-6 (B18C6), K+·B18C6. In the UV−UV HB spectra of the K+·B18C6 complex, gain signals are also observed; these are due to vibrationally hot K+·B18C6 complex produced by the UV excitation of cold K+·B18C6 complex. Then we apply UV−UV HB spectroscopy to the M+·B12C4 complexes, and only one conformer is found for each complex except for the Li+ complex, which has two conformers. The vibronic structure around the origin band of the UVPD spectra is quite similar for all the complexes, indicating close resemblance of the complex structure. The most stable structures calculated for the M+·B12C4 (M = Li, Na, K, Rb, and Cs) complexes also have a similar conformation among them, which coincides with the UVPD results. In these conformers the metal ions are too big to be included in the B12C4 cavity, even for the Li+ ion. In solution, it was reported that 12-crown-4 (12C4) shows the preference of Na+ ion among alkali metal ions. From the similarity of the structure for the M+·B12C4 complexes, it is suggested that the solvation of free metal ions, not of the M+·12C4 complexes, may lead to the selectivity of Na+ ion for 12C4 in solution.This work was partly supported by JSPS KAKENHI Grant Number 16H04098

Impaired Healing of a Cutaneous Wound in an Inducible Nitric Oxide Synthase-Knockout Mouse

Background. We investigated the effects of loss of inducible nitric oxide synthase (iNOS) on the healing process of cutaneous excisional injury by using iNOS-null (KO) mice. Population of granulation tissue-related cell types, that is, myofibroblasts and macrophages, growth factor expression, and reepithelialization were evaluated. Methods. KO and wild type (WT) mice of C57BL/6 background were used. Under general anesthesia two round full-thickness excision wounds of 5.0 mm in diameter were produced in dorsal skin. After specific intervals of healing, macroscopic observation, histology, immunohistochemistry, and real-time reverse transcription-polymerase chain reaction (RT-PCR) were employed to evaluate the healing process. Results. The loss of iNOS retards granulation tissue formation and reepithelialization in excision wound model in mice. Detailed analyses showed that myofibroblast appearance, macrophage infiltration, and mRNA expression of transforming growth factor b and of collagen 1α2 were all suppressed by lacking iNOS. Conclusions. iNOS is required in the process of cutaneous wound healing. Lacking iNOS retards macrophage invasion and its expression of fibrogenic components that might further impair fibrogenic behaviors of fibroblasts

CORRELATION BETWEEN THROWING MOTION AND MAXIMUM ELBOW VARUS TORQUE IN FEMALE PROFESSIONAL BASEBALL PITCHERS

The purpose of this study was to identify the correlation between throwing motion and maximum elbow varus torque (MEV) in female professional baseball pitchers. Twelve pitchers without pre-existing pain were recruited. Ball velocity and pitching motion were measured. Ball velocity and, kinematic and kinetic data from each joint during the pitch were extracted to evaluate the correlation with MEV. There was no correlation between the fastest ball velocity and MEV. Sixteen kinematic and kinetic parameters were found to have significant correlations with MEV. Particularly, as trunk rotation angle to the non-throwing direction before lead foot contact (FC) increased, the MEV decreased. Rotating the trunk in the non-throwing direction before FC and immediately in the throwing direction after FC could be a key component of the throwing motion

Lung interstitial cells during alveolarization

Recent progress in neonatal medicine has enabled survival of many extremely low-birth-weight infants. Prenatal steroids, surfactants, and non-invasive ventilation have helped reduce the incidence of the classical form of bronchopulmonary dysplasia characterized by marked fibrosis and emphysema. However, a new form of bronchopulmonary dysplasia marked by arrest of alveolarization remains a complication in the postnatal course of extremely low-birth-weight infants. To better understand this challenging complication, detailed alveolarization mechanisms should be delineated. Proper alveolarization involves the temporal and spatial coordination of a number of cells, mediators, and genes. Cross-talk between the mesenchyme and the epithelium through soluble and diffusible factors are key processes of alveolarization. Lung interstitial cells derived from the mesenchyme play a crucial role in alveolarization. Peak alveolar formation coincides with intense lung interstitial cell proliferation. Myofibroblasts are essential for secondary septation, a critical process of alveolarization, and localize to the front lines of alveologenesis. The differentiation and migration of myofibroblasts are strictly controlled by various mediators and genes. Disruption of this finely controlled mechanism leads to abnormal alveolarization. Since arrest in alveolarization is a hallmark of a new form of bronchopulmonary dysplasia, knowledge regarding the role of lung interstitial cells during alveolarization and their control mechanism will enable us to find more specific therapeutic strategies for bronchopulmonary dysplasia. In this review, the role of lung interstitial cells during alveolarization and control mechanisms of their differentiation and migration will be discussed

Persistent Left Superior Vena Cava in Hematological Malignancy Requiring Central Venous Catheter Insertion for Intensive Chemotherapy

Persistent left superior vena cava is a congenital vascular anomaly, which is possibly arrhythmogenic and thrombogenic, rarely complicated with coronary sinus atresia. We treated a 42-year-old male with Hodgkin's lymphoma requiring central venous catheter placement for intensive chemotherapy. Persistent left superior vena cava was revealed after the insertion of the central venous catheter by the radiological finding of the catheter tip cannulated into the vena cava cavity. The relationship between coronary sinus atresia and persistent left superior vena cava induced by central venous catheterization remains unclear; however, the hematologist should pay attention to the malpositioning of the central venous catheter

Vitrectomy for Proliferative Diabetic Retinopathy in a Patient with Heparin-Induced Thrombocytopenia

Introduction: In this study, we report a case of proliferative diabetic retinopathy in a patient with heparin-induced thrombocytopenia (HIT) in whom vitrectomy was performed with good results. Case: A 57-year-old man presented with a chief complaint of decreased visual acuity (VA) in the left eye. Corrected VA of the left eye was 0.03, and ophthalmic examination showed fibrovascular membranes along the vascular arcade and a combined rhegmatogenous-traction retinal detachment with a macular hole. The patient began hemodialysis for diabetic nephropathy in March 2014; thrombocytopenia developed after dialysis was started, and HIT was diagnosed after further evaluation. Argatroban hydrate was being used during dialysis. Treatment was switched from warfarin to argatroban hydrate 6 days prior to vitrectomy being performed on the patient's left eye. Although there was bleeding with somewhat difficult hemostasis during the intraoperative treatment of the fibrovascular membranes, surgery was completed without complications and the postoperative course was good. Discussion: Vitrectomy was performed with good results in this patient with HIT. Treatment with argatroban hydrate during surgery enabled surgery without the danger of intraoperative clotting

Inhibition of the CoREST Repressor Complex Promotes Wound Re-Epithelialization through the Regulation of Keratinocyte Migration

Wound healing is a complex process involving phases of hemostasis, inflammation, proliferation, and remodeling. The regenerative process in the skin requires coordination between many regulators, including signaling molecules, transcription factors, and the epigenetic machinery. In this study, we show that chromatin regulators HDAC1 and LSD1, key components of the CoREST repressor complex, are upregulated in the regenerating epidermis during wound repair. We also show that corin, a synthetic dual inhibitor of the CoREST complex and HDAC1/LSD1 activities, significantly accelerates wound closure through enhanced re-epithelialization in a mouse tail wound model. Acetylated H3K9 (methylation of histone H3 at lysine 9) expression, a histone modification targeted by HDAC1, is increased in keratinocytes after topical treatment with 100 nM and 1 μM of corin. In vitro experiments demonstrate that corin promotes migration and inhibits the proliferation of human keratinocytes. Furthermore, expression levels of genes promoting keratinocyte migration, such as AREG, CD24, EPHB2, ITGAX, PTGS, SCT1, SERPINB2, SERPINE1, SLPI, SNAI2, and TWIST, increased in keratinocytes treated with corin. These data demonstrate that dual inhibition of class I histone deacetylases and LSD1 by corin may serve as a new approach for promoting wound re-epithelialization and provide a platform for further applications of corin for the treatment of chronic wounds