Hydrocarboxyl Radical as a Product of α-Alanine Ultraviolet Photolysis.

UV photodissociation of α-alanine was studied by parahydrogen matrix isolation infrared spectroscopy. The temporal behavior of Fourier transform infrared spectra revealed that UV irradiation at 213 nm yielded the HOCO radical as a direct photoproduct from the S2 excited state. The concentration of HOCO quickly approached a steady state due to secondary photodissociation of HOCO to produce CO2 + H or CO + OH. On the other hand, no photoproducts were detected by S1 excitation at 266 nm. Irradiation of fully deuterated α-alanine at 213 nm yielded ∼2 times more cis-DOCO radicals than the lower energy isomer trans-DOCO, indicating that the conformation of the hydroxyl group is fairly well-preserved upon photodissociation of α-alanine. The present study suggests that HOCO may be a good tracer species in the search for amino acids in interstellar space.

Dual-Targeting Glycol Chitosan/Heparin-Decorated Polypyrrole Nanoparticle for Augmented Photothermal Thrombolytic Therapy.

Near-infrared (NIR)-light-modulated photothermal thrombolysis has been investigated to overcome the hemorrhage danger posed by clinical clot-busting substances. A long-standing issue in thrombosis fibrinolytics is the lack of lesion-specific therapy, which should not be ignored. Herein, a novel thrombolysis therapy using photothermal disintegration of a fibrin clot was explored through dual-targeting glycol chitosan/heparin-decorated polypyrrole nanoparticles (GCS-PPY-H NPs) to enhance thrombus delivery and thrombolytic therapeutic efficacy. GCS-PPY-H NPs can target acidic/P-selectin high-expression inflammatory endothelial cells/thrombus sites for initiating lesion-site-specific thrombolysis by hyperthermia using NIR irradiation. A significant fibrin clot-clearance rate was achieved with thrombolysis using dual-targeting/modality photothermal clot disintegration in vivo. The molecular level mechanisms of the developed nanoformulations and interface properties were determined using multiple surface specific analytical techniques, such as particle size distribution, zeta potential, electron microscopy, Fourier-transform infrared spectroscopy (FTIR), wavelength absorbance, photothermal, immunofluorescence, and histology. Owing to the augmented thrombus delivery of GCS-PPY-H NPs and swift treatment time, dual-targeting photothermal clot disintegration as a systematic treatment using GCS-PPY-H NPs can be effectively applied in thrombolysis. This novel approach possesses a promising future for thrombolytic treatment.

Complicated skin and soft tissue infection with Mycobacterium fortuitum following excision of a sebaceous cyst in Taiwan.

Mycobacterium fortuitum group (M. fortuitum), also known as rapidly growing Mycobacteria, can cause pyogenic infections in human beings, most commonly in immunocompromised patients. Herein, we present a 40-year-old immunocompetent male patient who underwent planned excision of a sebaceous cyst in the abdominal wall. He suffered from tender erythematous lesions with purulent discharge around the healing wound that developed 2 weeks after surgery. Gram stain, bacterial and fungal culture results of the wound were negative. A diagnosis of non-tuberculous mycobacteria was made from a wound culture from the area of operative debridement, which was subsequently confirmed to be M. fortuitum group using PCR-restriction fragment length polymorphism analysis of the hsp65 gene. The patient received 4 weeks of parenteral imipenem/cilastatin 500 mg every 6 hours and amikacin 500 mg every 12 hours, plus oral clarithromycin 500 mg twice daily, and the wound recovered completely. He was discharged and followed up regularly at our outpatient clinic, and continued taking oral ciprofloxacin and clarithromycin 500 mg twice daily for 6 months. This case highlights the importance of strict aseptic precautions even during minor procedures, and also the characteristics of M. fortuitum infections in immunocompetent patients, which usually develop as localized postsurgical wound infections. We also share our experience in successfully treating a M. fortuitum complicated skin and soft tissue infection.

Erythropoiesis suppression is associated with anthrax lethal toxin-mediated pathogenic progression.

Anthrax is a disease caused by the bacterium Bacillus anthracis, which results in high mortality in animals and humans. Although some of the mechanisms are already known such as asphyxia, extensive knowledge of molecular pathogenesis of this disease is deficient and remains to be further investigated. Lethal toxin (LT) is a major virulence factor of B. anthracis and a specific inhibitor/protease of mitogen-activated protein kinase kinases (MAPKKs). Anthrax LT causes lethality and induces certain anthrax-like symptoms, such as anemia and hypoxia, in experimental mice. Mitogen-activated protein kinases (MAPKs) are the downstream pathways of MAPKKs, and are important for erythropoiesis. This prompted us to hypothesize that anemia and hypoxia may in part be exacerbated by erythropoietic dysfunction. As revealed by colony-forming cell assays in this study, LT challenges significantly reduced mouse erythroid progenitor cells. In addition, in a proteolytic activity-dependent manner, LT suppressed cell survival and differentiation of cord blood CD34(+)-derived erythroblasts in vitro. Suppression of cell numbers and the percentage of erythroblasts in the bone marrow were detected in LT-challenged C57BL/6J mice. In contrast, erythropoiesis was provoked through treatments of erythropoietin, significantly ameliorating the anemia and reducing the mortality of LT-treated mice. These data suggested that suppressed erythropoiesis is part of the pathophysiology of LT-mediated intoxication. Because specific treatments to overcome LT-mediated pathogenesis are still lacking, these efforts may help the development of effective treatments against anthrax.