Case report: Transient lactate elevation by intravenous insulin infusion therapy for diabetic ketoacidosis in a patient with mitochondrial DNA 3243 A > G mutation: A glycolysis rebooting syndrome?

Mitochondrial disease, most cases of which are caused by mitochondrial DNA (mtDNA) mutation, is present with multiple phenotypes including diabetes mellitus, sensorineural hearing loss, cardiomyopathy, muscle weakness, renal dysfunction, and encephalopathy, depending on the degree of heteroplasmy. While mitochondria play an important role in intracellular glucose and lactate metabolism in insulin-sensitive tissues such as muscles, appropriate strategies for glycemic control have not yet been established in a patient with mitochondrial disease, which is often complicated by myopathy. Here, we describe the history of a 40-year-old man with mtDNA 3243A > G who had sensorineural hearing loss, cardiomyopathy, muscle wasting, and diabetes mellitus with stage 3 chronic kidney disease. He developed mild diabetic ketoacidosis (DKA) in the process of treatment for poor glycemic control with severe latent hypoglycemia. According to the standard therapy for DKA, he was treated with continuous intravenous insulin infusion therapy, which unexpectedly resulted in an abrupt and transient elevation in blood lactate levels without exacerbation of heart failure and kidney function. Since blood lactate levels are determined by the balance between lactate production and consumption, an abrupt and transient lactate elevation following intravenous insulin injection therapy may reflect not only enhanced glycolysis in insulin-sensitive tissues with mitochondrial dysfunction but also decreased lactate consumption in the sarcopenic skeletal muscle and failing heart. Intravenous insulin infusion therapy in patients with mitochondrial disease may unmask derangements of intracellular glucose metabolism in response to insulin signaling

Structures and energetics of Bi_{2}O_{3} polymorphs in a defective fluorite family derived by systematic first-principles lattice dynamics calculations

A series of dynamically stable structures of the defective fluorite-Bi2O3 is found by first-principles lattice dynamics calculations. The crystal symmetry is lowered and local distortion is included systematically along imaginary modes of lattice vibrations. A clear band gap appears when local distortion is included in this way, which is consistent with experimental results. Many theoretical calculations in the past indicated metallic or semimetallic electronic structures. The appropriate inclusion of the symmetry breaking and local distortion are therefore essential in reproducing the electronic structures of Bi2O3. The three stable structures are found to have an energy of 0.07–0.08 eV/f.u. relative to α-Bi2O3. The arrays of oxide-ion vacancies in two of these structures are the same as those of β-Bi2O3 and ε-Bi2O3, which were experimentally identified as stable phases. A bixbyite-type vacancy-array structure is also found to be another stable phase in the present study, which is named η-Bi2O3. It is suggested that the three stable structures of Bi2O3 are ordered low-temperature polymorphs of the disordered δ-Bi2O3 in the defective fluorite-Bi2O3 family

Electronic structures of dynamically stable As2O3, Sb2O3, and Bi2O3 crystal polymorphs

The relationships between the atomic arrangements, electronic structures, and energetics of three sesquioxides, As2O3, Sb2O3, and Bi2O3, are systematically investigated by first-principles lattice-dynamics calculations. Dynamically stable structures of the defective fluorite family are searched for by including atomic displacements along imaginary modes of lattice vibrations that appear in high-symmetry structures. Experimentally reported crystal structures (arsenolite-As2O3, α-Sb2O3, β-Sb2O3, and β-Bi2O3) are found to be formed by symmetry breaking and local atomic distortion in this way. Moreover, some dynamically stable structures that have not yet been revealed by experiments are discovered. Their electronic structures and the magnitudes of their band gaps are obtained. In the dynamically stable low-symmetry structures, valence electrons localize and form an asymmetric charge distribution along the direction of an empty anion site of the defective fluorite structure. This is a common characteristic of a "lone pair" of cations. The formation of the lone pair is less significant in the order As2O3, Sb2O3, Bi2O3, which is the same trend as the lattice distortion. The formation of the lone pair plays an essential role in determining the structures, stability, and properties of these sesquioxides

Impact of the COVID-19 pandemic on COPD exacerbations in Japanese patients: a retrospective study

Abstract Various infection control measures implemented during the coronavirus disease (COVID-19) pandemic have reduced the number of respiratory infections, which are the most common cause of chronic obstructive pulmonary disease (COPD) exacerbations. Here, we investigated whether infectious disease prevention during the COVID-19 pandemic reduced COPD exacerbations and the characteristics of patients exhibiting exacerbations before and during the COVID-19 pandemic. We included outpatients and inpatients with moderate or severe COPD exacerbations who required systemic steroids between April 1, 2018 and March 31, 2022. Their medical records were retrospectively compared and analyzed in 2-year intervals (before and during the COVID-19 pandemic). During the 4-year observation period, 70,847 outpatients and 2,772 inpatients were enrolled; 55 COPD exacerbations were recorded. The number of COPD exacerbations decreased from 36 before to 19 during the COVID-19 pandemic. Regarding the characteristics of patients with exacerbations, the % forced expiratory volume in one second (52.3% vs. 38.6%, P = 0.0224) and body mass index (BMI) (22.5 vs. 19.3, P = 0.0127) were significantly lower during the COVID-19 pandemic than before the pandemic. The number of COPD exacerbations during the pandemic decreased. Additionally, the tendency for a reduction in COPD exacerbation was greatest in patients with preserved lung function or above-standard BMI patients

Circulating levels of human salusin-β, a potent hemodynamic and atherogenesis regulator.

Using bioinformatics analysis, we previously identified salusin-β, an endogenous bioactive peptide with diverse physiological activities. Salusin-β is abundantly expressed in the neuroendocrine system and in systemic endocrine cells/macrophages. Salusin-β acutely regulates hemodynamics and chronically induces atherosclerosis, but its unique physicochemical characteristics to tightly adhere to all types of plastic and glassware have prevented elucidation of its precise pathophysiological role. To quantitate plasma total salusin-β concentrations, we produced rabbit and chicken polyclonal antibodies against the C- and N-terminal end sequences, circumvented its sticky nature, and successfully established a sandwich enzyme-linked immunosorbent assay (ELISA). Salusin-β was abundantly present in the plasma of healthy volunteers, ranging from 1.9 to 6.6 nmol/L. Reverse phase-high performance liquid chromatography analysis showed that a single immunoreactive salusin-β peak coincided with synthetic authentic salusin-β. Plasma salusin-β concentrations were unaffected by postural changes and by potent vasopressin release stimuli, such as hypertonic saline infusion or smoking. However, salusin-β concentrations showed significant circadian variation; concentrations were high during the daytime and reached the lowest concentrations in the early morning. Plasma salusin-β levels in subjects with diabetes mellitus, coronary artery disease, and cerebrovascular disease showed distinctly higher levels than healthy controls. Patients with panhypopituitarism combined with complete central diabetes insipidus also showed significantly higher plasma salusin-β levels. Therefore, the ELISA system developed in this study will be useful for evaluating circulating total salusin-β levels and for confirming the presence of authentic salusin-β in human plasma. The obtained results suggest a limited contribution of the neuroendocrine system to peripheral total salusin-β concentrations and a role for plasma total salusin-β concentrations as an indicator of systemic vascular diseases