Kobe Journal of Medical Sciences最新文献

Piezo1, a mechanosensitive ion channel that opens in response to mechanical stimuli, is widely expressed among mammalian cell types, and regulates a diverse range of physiological processes. Although evidence has suggested potential clinical benefit of Piezo1 activation for various conditions, the safety and efficacy of such activation in living animals have remained unclear. To investigate the therapeutic potential of Piezo1 activation, we here generated genetically modified mouse models in which Piezo1 is overexpressed either specifically in skeletal muscle or systemically in response to tamoxifen treatment in adult animals. Cast immobilization induced a reduction in both muscle mass and the abundance of Piezo1 mRNA in skeletal muscle of the affected limbs in control mice. Overexpression of Piezo1 in skeletal muscle prevented the immobilization-induced reduction both in soleus muscle mass and in the corresponding cross-sectional area of myofibers, suggesting the potential benefit of Piezo1 activation for prevention of immobilization-induced muscle atrophy. Furthermore, mice with systemic overexpression of Piezo1 showed no apparent abnormalities in growth or general activity. Red blood cells from these mice manifested slight resistance to hypoosmolarity-induced hemolysis, and the animals did not develop apparent hemolytic anemia. Our findings demonstrate promising efficacy and safety of Piezo1 activation in living animals and thereby highlight the therapeutic potential of targeting the Piezo1 signaling pathway.

Intermittent hypoxia (IH) can aggravate non-alcoholic fatty liver disease (NAFLD) by activating hypoxia-inducible Factor-α and increasing oxidative stress. Lipid peroxidation, which occurs as a consequence of reactive oxygen species (ROS) generation, is characterized by malondialdehyde (MDA) formation and decreased catalase (CAT) and superoxide dismutase (SOD) levels. Hence, inadequate management of NAFLD might induce cognitive impairment. However, although studies have shown that Ficus carica could prevent cognitive impairment due to NAFLD complications, the mechanism by which this is achieved remains unclear. The current study therefore aimed to clarify the effects of Ficus carica in suppressing cognitive impairments caused by hypoxia-induced NAFLD. Sprague-Dawley male rats were divided into five groups: negative control positive control (PC), and IH with Ficus carica treatment (6.25, 12.5, and 25 mL/kg/day) for 4 weeks before and 1 week during IH. Rats were exposed to IH exposure by placing them in a hypoxic chamber (90% N₂ and 10% O₂) for 7 days. Regardless of dosage, Ficus carica treatment reduced MDA levels when compared to PC, and low-dose increased liver SOD levels more than the other groups. In contrast, the medium Ficus carica dose was associated with increased CAT activity and decreased inflammatory marker levels compared to the other treatments. Meanwhile, the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic immune-inflammation index were all greatest in the medium-dose group. The PC group showed a significant decrease in the percentage of alteration. Our data implies that medium doses of Ficus carica can reduce cognitive impairment caused by hypoxia-induced NAFLD.

SARS-CoV-2 Omicron sub-variants are still emerging and become highly diversified, resulting in increased transmissibility and immune evasion ability. Neutralizing antibody is very important to fight against the variants. However, the ability of neutralizing antibody induced by early SARS-CoV-2 (D614G) primary infection has not been analyzed in detail against lately emerged Omicron variants, such as BA.5 and EG.5.1. In this study the sera from severe/critically infected patients of D614G were investigated the potency of neutralization activity against SARS-CoV-2 BA.5 and EG.5.1 by using live virus neutralization assay. The neutralizing activity was observed and analyzed in detail from day 1 until 7 post infection. The sera of both severe and critical patients showed cross neutralizing activity for BA.5, and even for EG.5.1. It is suggested that neutralizing antibodies targeting conserved epitopes are partly induced upon the primary infection as the result of robust immune response.

This study aimed to explore the association between commuting distance using public transportation and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody-positivity among medical staff at a cardiovascular medical institution in Japan. Information on the commuting distance using public transportation, grouped into none, short (<11.3 km; median), and long (≥11.3 km); demographics; and the coronavirus disease 2019 (COVID-19) exposure were cross-sectionally collected from 956 employees in June 2022. SARS-CoV-2 antibody-positivity was defined based on serological tests for the nucleocapsid protein antigen. Among all participants (mean age 36 years; 68.6% female), 118 (12.3%) had SARS-CoV-2 antibody-positivity. Participants with long commuting distances were more likely to have ≥3 household members. Compared with non-use of public transportation, neither short nor long commuting distances by public transportation were associated with antibody-positivity (adjusted odds ratio 1.18 [95% confidence interval 0.70-1.98] and 1.62 [0.97-2.71], respectively). In participants with ≤2 household members (n = 706 [73.8%]; mean age 37 years; 72.4% female), a long commuting distance was associated with SARS-CoV-2 positivity compared with non-use of public transportation (1.98 [1.02-3.84]). In conclusion, commuting distance using public transportation was not associated with SARS-CoV-2 antibody-positivity in general; however, it may be relevant among healthcare workers with fewer household members.

Purpose: Under general anesthesia, lidocaine shortens the onset time of vecuronium but it does not affect that of rocuronium. We suspected that the dose of rocuronium used in previous reports, 0.6 mg/kg, was too high to detect any difference due to lidocaine's effect. We investigated the effects of 1.5 mg/kg lidocaine on the onset time, 50% depression time, 100% depression time, and duration of action of 0.4 mg/kg rocuronium.

Methods: Sixty adult patients who underwent elective operation under general anesthesia without tracheal intubation were randomly divided into two groups: including a lidocaine group (LG) and a placebo group (PG). Anesthesia was induced and maintained using propofol and remifentanil. After the loss of consciousness, a supraglottic device was inserted. After the neuromuscular monitor was calibrated, measurements were initiated with train-of-four stimulation at 20-second intervals, and 1.5 mg/kg lidocaine and the same volume of physiological saline were administered to the LG and the PG respectively. Ten seconds after the next train-of-four stimulation, 0.4 mg/kg rocuronium was administered.

Results: The mean (standard deviation) onset time (seconds) between the LG and PG were 368.0 (170.5) and 314.8 (161.1), respectively, with no significant difference ( p = 0.24). There were no significant differences between the groups in terms of the 50% depression time ( p = 0.71), 100% depression time ( p = 0.53), or duration of action ( p = 0.45).

Conclusion: The pre-administration of 1.5 mg/kg lidocaine did not affect the onset time, 50% depression time, 100% depression time, or duration of action of 0.4 mg/kg rocuronium.

Aim: Our previous studies identified ultraviolet B (UVB) irradiation as a possible approach for preventing atherosclerosis. The aim of this study was to clarify the effect of 312 nm UVB, a wavelength similar to that of clinically available narrow-band UVB for the treatment of psoriasis, on atherosclerosis and the underlying mechanisms.

Methods and results: Using a recently developed UVB-light-emitting diode device, we irradiated 6-week-old male atherosclerosis-prone apolipoprotein E-deficient mice with 312 nm UVB at 5 or 10 kJ/m² and examined its effect on the development of atherosclerosis and immunoinflammatory responses by performing histological analysis, flow cytometry, biochemical assays, and liquid chromatography/mass spectrometry-based lipidomics. UVB irradiation at 10 kJ/m² but not at 5 kJ/m² significantly attenuated the development of aortic root atherosclerotic plaques, while UVB irradiation at both doses induced a less inflammatory plaque phenotype. This atheroprotective effect was associated with a reduced effector T cell number, a shift toward anti-atherogenic helper T cell responses, and increased proportion of regulatory T cells in lymphoid tissues and increased levels of proresolving lipid mediators in the skin.

Conclusions: We demonstrated that 312 nm UVB irradiation limits atherosclerosis by favorably modulating the T cell balance and lipid mediator profile. Our findings indicate that 312 nm UVB phototherapy could be an attractive immunomodulatory approach for preventing and treating atherosclerosis.

A woman in her 70s who was taking warfarin 3.75 mg/day had a prothrombin time-international normalized ratio (PT-INR) within the therapeutic range. Her medication for pulmonary hypertension was changed from bosentan to macitentan. After 40 days, she developed respiratory distress, anorexia, and vomiting caused by common cold. When she visited the pharmaceutical outpatient clinic without reservation, the pharmacist suspected that bosentan discontinuation, which cancelled cytochrome P450 (CYP) 2C9 and CYP3A4 enzyme induction, and decreased vitamin K intake due to appetite loss had enhanced warfarin effect, causing PT-INR prolongation. The pharmacist requested the physician to examine the patient's PT-INR. Results showed that her PT-INR was >7. Hence, she was urgently hospitalized. Warfarin and macitentan were discontinued, and the patient's PT-INR decreased to 1.77 after the intravenous administration of vitamin K. Her appetite improved, and warfarin 2 mg/day was resumed. Additionally, when she had been administered macitentan, her hemoglobin levels decreased from 10.8 to 6.6 mg/dL. Therefore, the pharmacist and the physician during hospitalization planned to resume treatment with bosentan, but not with macitentan. The pharmacist proposed to increase the warfarin dose to 3.75 mg since the bosentan and warfarin interaction could lower PT-INR. Thereafter, the patient's PT-INR was controlled within the therapeutic range, and her hemoglobin level was 8-9 mg/dL. The patient was discharged on day 17 of admission. Thus, pharmacist intervention plays a significant role in warfarin control with consideration of drug-drug interaction in patients receiving pulmonary hypertension treatment.

Objectives: To analyse the association of anti-dsDNA Ab with patient-reported outcomes (PROs) in patients with SLE under maintenance treatment, as it has not been clearly understood whether PROs are able to be reflected by anti-dsDNA, which are associated with SLE activities (SLE Disease Activity Index 2000, SLEDAI-2K).

Methods: The SLE symptom checklist (SSC), LupusPRO, Medical Outcomes Study Short Form-36 (SF-36), and patient and physician visual analogue scale (Pt/Ph-VAS) at a time point were evaluated for correlation with anti-dsDNA using the Kyoto Lupus Cohort Registry (n = 310) from 2019 to 2020. Further, associations between changes in anti-dsDNA with those in Pt/Ph-VAS and SSC at two time points of short-term (3 months) or long-term (2 years) time points.

Results: Cross-sectionally, anti-dsDNA slightly correlated with Ph-VAS (ρ = 0.18, p = 0.003) and SLEDAI-2K (ρ = 0.14, p = 0.03), while anti-dsDNA was not correlated with SSC, SF-36, and LupusPRO, or Pt-VAS. In short-term and long-term, anti-dsDNA demonstrated no significant correlation with alterations in SSC, Pt-VAS, or Ph-VAS. Further, they did not show associations when SLE activities (SLEDAI-2K) were worsened.

Conclusion: PROs at a time point and changes were difficult to be captured by anti-dsDNA. It is desirable to explore objective laboratory measures to evaluate PROs.

The coronavirus disease 2019 (COVID-19) pandemic has affected people worldwide, and pediatric patients with underlying diseases are at high risk of developing severe COVID-19. However, there are limited reports on the clinical impact of COVID-19, especially in patients with underlying neuromuscular diseases (NMD) and inborn errors of metabolism (IEM). This study aimed to investigate the incidence and clinical presentation of COVID-19 in patients with NMD and IEM. This was a single-center, cross-sectional study of patients with NMD and IEM in Japan for 2 years, from April 1, 2020 to March 31, 2022. Among 255 participants with a median age of 14 (range: 0-50) years, 192 (75%) and 63 (25%) had NMD and IEM, respectively. Among 255 patients, 8 (5 NMD and 3 IEM) were positive for the anti-severe acute respiratory syndrome coronavirus 2 nucleocapsid antibody, and the incidence was considered 3%. All positive patients had mild or asymptomatic COVID-19. None of the patients exhibited moderate or severe symptoms. In conclusion, this study revealed that the incidence of COVID-19 was low, and mild or subclinical infection was common even in patients with NMD and IEM, who may be at a higher risk of severe COVID-19.

Purpose: Liver fibrosis is not thought to occur in patients with no adverse events after surgery for congenital biliary dilatation (CBD). However, this speculation is not supported by any reports. Real-time shear wave elastography (SWE) is a noninvasive, ultrasound-based technique to evaluate liver stiffness. We aimed to clarify the presence of liver fibrosis using SWE in patients who had undergone surgery for CBD.

Methods: We included patients who underwent radical surgery for CBD, who were followed up until March 2022, and have been performed with SWE at our institution from April 2021 to March 2022. Liver stiffness was evaluated using SWE, and liver fibrosis stages (F0-F4; METAVIR scoring) were determined based on the previously reported associations between liver stiffness and liver fibrosis. We assessed the general condition of each patient and performed routine blood investigations on the same day as SWE.

Results: Two out of 20 patients had long-term complications (intrahepatic stones without symptoms [n = 1], recurrent cholangitis [n = 1]). The median hepatic shear wave propagation velocity was 1.26 (range, 1.12-1.60) m/s in all cases. The estimated liver fibrosis stage was ≤F1 in patients without long-term complications. In patient with recurrent cholangitis, the hepatic shear wave propagation velocity was 1.60 m/s, and the estimated liver fibrosis stage was F3.

Conclusion: Liver fibrosis tended not to occur in patients with no complications after surgery for CBD. However, patients with long-term postoperative complications, such as cholangitis, should be examined using SWE so as not to overlook liver cirrhosis.