High-flow nasal cannula oxygen therapy was effective for dysphagia associated with respiratory muscle paralysis due to cervical spinal cord injury: A case report.

RATIONALE: Respiratory muscle paralysis due to low cervical spinal cord injury (CSCI) can lead to dysphagia. Noninvasive positive airway pressure (PAP) therapy can effectively treat this type of dysphagia. High-flow nasal cannula (HFNC) oxygen therapy can generate a low level of positive airway pressure resembling PAP therapy, it may improve the dysphagia. PATIENT CONCERNS: The patient was an 87-year-old man without preexisting dysphagia. He suffered a CSCI due to a dislocated C5/6 fracture, without brain injury, and underwent emergency surgery. Postoperatively (day 2), he complained of dysphagia, and the intervention was initiated. DIAGNOSIS: Based on clinical findings, dysphagia in this case, may have arisen due to impaired coordination between breathing and swallowing, which typically occurs in patients with CSCI who have reduced forced vital capacity. INTERVENTIONS: HFNC oxygen therapy was started immediately after the surgery, and swallowing rehabilitation was started on Day 2. Indirect therapy (without food) and direct therapy (with food) were applied in stages. HFNC oxygen therapy appeared to be effective because swallowing function temporarily decreased when the HFNC oxygen therapy was changed to nasal canula oxygen therapy. OUTCOMES: Swallowing function of the patient improved and he did not develop aspiration pneumonia. LESSONS: HFNC oxygen therapy improved swallowing function in a patient with dysphagia associated with respiratory-muscle paralysis following a CSCI. It may have prolonged the apnea tolerance time during swallowing and may have improved the timing of swallowing. HFNC oxygen therapy can facilitate both indirect and direct early swallowing therapy to restore both swallowing and respiratory function.

Muraminomicins, new lipo-nucleoside antibiotics from Streptosporangium sp. SANK 60501-structure elucidations of muraminomicins and supply of the core component for derivatization.

We screened for bacterial phospho-N-acetylmuramyl-pentapeptide-translocase (MraY: EC 2.7.8.13) inhibitors with the aim of discovering novel antibiotics and observed inhibitory activity in the culture broth of an actinomycete, SANK 60501. The active compounds, muraminomicins A, B, C, D, E1, E2, F, G, H, and I exhibited strong inhibitory activity against MraY with IC50 values of 0.0105, 0.0068, 0.0104, 0.0099, 0.0115, 0.0109, 0.0089, 0.0134, 0.0186, and 0.0094 µg ml-1, respectively. Although muraminomicin F exhibited favorable antibacterial activity against drug-resistant Gram-positive bacteria, this activity was reduced with the addition of serum. To efficiently supply the core component for chemical modification studies, production was carried out in a controlled trial by adding myristic acid to the medium, and a purification method suitable for large-scale production was successfully developed.

Novel Nrf2 activators from microbial transformation products inhibit blood-retinal barrier permeability in rabbits.

BACKGROUND AND PURPOSE: Nuclear factor erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that binds to antioxidant response elements located in the promoter region of genes encoding many antioxidant enzymes and phase II detoxifying enzymes. Activation of the Nrf2 pathway seems protective for many organs, and although a well-known Nrf2 activator, bardoxolone methyl, was evaluated clinically for treating chronic kidney disease, it was found to induce adverse events. Many bardoxolone methyl derivatives, mostly derived by chemical modifications, have already been studied. However, we adopted a biotransformation technique to obtain a novel Nrf2 activator. EXPERIMENTAL APPROACH: The potent novel Nrf2 activator, RS9, was obtained from microbial transformation products. Its Nrf2 activity was evaluated by determining NADPH:quinone oxidoreductase-1 induction activity in Hepa1c1c7 cells. We also investigated the effects of RS9 on oxygen-induced retinopathy in rats and glycated albumin-induced blood-retinal barrier permeability in rabbits because many ocular diseases are associated with oxidative stress and inflammation. KEY RESULTS: Bardoxolone methyl doubled the specific activity of Nrf2 in Hepa1c1c7 cells at a much higher concentration than RS9. Moreover, the induction of Nrf2-targeted genes was observed at a one-tenth lower concentration of RS9. Interestingly, the cytotoxicity of RS9 was substantially reduced compared with bardoxolone methyl. Oral and intravitreal administration of RS9 ameliorated the pathological scores and leakage in the models of retinopathy in rats and ocular inflammation in rabbits respectively. CONCLUSION AND IMPLICATIONS: Nrf2 activators are applicable for treating ocular diseases and novel Nrf2 activators have potential as a unique method for prevention and treatment of retinovascular disease.

Synechocystis DrgA protein functioning as nitroreductase and ferric reductase is capable of catalyzing the Fenton reaction.

In order to identify an enzyme capable of Fenton reaction in Synechocystis, we purified an enzyme catalyzing one-electron reduction of t-butyl hydroperoxide in the presence of FAD and Fe(III)-EDTA. The enzyme was a 26 kDa protein, and its N-terminal amino acid sequencing revealed it to be DrgA protein previously reported as quinone reductase [Matsuo M, Endo T and Asada K (1998) Plant Cell Physiol39, 751-755]. The DrgA protein exhibited potent quinone reductase activity and, furthermore, we newly found that it contained FMN and highly catalyzed nitroreductase, flavin reductase and ferric reductase activities. This is the first demonstration of nitroreductase activity of DrgA protein previously identified by a drgA mutant phenotype. DrgA protein strongly catalyzed the Fenton reaction in the presence of synthetic chelate compounds, but did so poorly in the presence of natural chelate compounds. Its ferric reductase activity was observed with both natural and synthetic chelate compounds with a better efficiency with the latter. In addition to small molecular-weight chemical chelators, an iron transporter protein, transferrin, and an iron storage protein, ferritin, turned out to be substrates of the DrgA protein, suggesting it might play a role in iron metabolism under physiological conditions and possibly catalyze the Fenton reaction under hyper-reductive conditions in this microorganism.