Like other substrates, plasma glucose is in a dynamic state of constant turnover (i.e., rates of glucose appearance [Ra glucose] into and disappearance [Rd glucose] from the plasma) while staying within a narrow range of normal concentrations, a physiological priority. Persistent imbalance of glucose turnover leads to elevations (i.e., hyperglycemia, Ra>Rd) or falls (i.e., hypoglycemia, Ra

Transglutaminase 2 (TG2) is a ubiquitously expressed enzyme that catalyzes crosslinking, polyamination or deamidation of glutamine residues in proteins. It has been reported that TG2 is involved in the pathogenesis of various inflammatory diseases including celiac disease, pulmonary fibrosis, cystic fibrosis, multiple sclerosis and sepsis. Recently, using a mouse model of bleomycin-induced lung fibrosis, we showed that TG2 is required to trigger inflammation via the induction of T helper type 17 (Th17) cell differentiation in response to tissue damage. However, the role of TG2 in inflammatory bowel disease (IBD), which is thought to be a Th17 cell-associated disease, has remained elusive. In this study, we investigated the role of TG2 in dextran sulfate sodium (DSS)-induced colitis, the most widely used mouse model for IBD. Age- and sex-matched wild-type and TG2(−/−) mice were fed 2% DSS for 7 days or 3.5% DSS for 5 days in drinking water. An in situ TG activity assay revealed that DSS treatment activates TG2 in various colon cell types, including columnar absorptive cells and goblet cells. DSS-treated TG2(−/−) mice showed lower interleukin (IL)-6, but higher IL-17A and RORγt (retinoic acid receptor-related orphan receptor-γt) expression levels in the colon tissues than that in the wild-type mice. Moreover, TG2(−/−) mice showed higher mortality than the wild-type mice because of DSS treatment. Nevertheless, we found no significant differences in changes of body weight, colon length, morphology, immune cell infiltration and in vivo intestinal permeability between DSS-treated wild-type and TG2(−/−) mice. These results indicate that TG2-mediated Th17 cell differentiation is not required for the pathogenesis of DSS-induced acute colitis.
Animals ; Body Weight ; Celiac Disease ; Cell Differentiation ; Child ; Child, Orphaned ; Colitis* ; Colon ; Cystic Fibrosis ; Dextran Sulfate* ; Dextrans* ; Drinking Water ; Fibrosis ; Glutamine ; Goblet Cells ; Humans ; Inflammation ; Inflammatory Bowel Diseases ; Interleukin-17 ; Interleukins ; Lung ; Mice* ; Mortality ; Multiple Sclerosis ; Permeability ; Pulmonary Fibrosis ; Sepsis ; Th17 Cells

Donepezil is a centrally acting, reversible acetylcholinesterase inhibitor that is widely used for treating Alzheimer's disease. This study aimed to compare the pharmacokinetics of Bastia(R), a test tablet formulation of donepezil hydrochloride 10 mg, with those of Aricept(R), the reference tablet formulation of donepezil hydrochloride 10 mg, in healthy Korean male volunteers. A randomized, single-dose, two-way crossover study was conducted in 32 subjects. Subjects received a single dose of either test or reference compound and the alternate drug after a 4-week washout period. Serial blood samples for pharmacokinetic analysis were collected prior to dosing and periodically for 288 h after dosing for measurement of the plasma concentrations of donepezil. A non-compartmental method was used to estimate the pharmacokinetic parameters. The maximum concentration (C(max)) and the area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC(288h)) for the two formulations were compared to evaluate bioequivalence. The C(max) of the test and reference drugs were 27.58+/-7.46 and 26.35+/-6.51 microg/L (mean+/-SD), respectively, while AUC(288h) was 1080.14+/-229.77 and 1043.07+/-242.28 microg.h/L (mean+/-SD), respectively. The geometric mean ratios (90% confidence interval) of the C(max) and AUC(288h) of the two tablets were 1.043 (0.990-1.099) and 1.039 (1.013-1.065). In conclusion, the newly formulated tablet of donepezil hydrochloride 10 mg is bioequivalent to the currently marketed 10 mg tablet.
Acetylcholinesterase ; Alzheimer Disease ; Cross-Over Studies ; Humans ; Male ; Pharmacokinetics ; Plasma ; Tablets ; Therapeutic Equivalency* ; Volunteers*

BACKGROUND: Frontal sinus fractures, particularly anterior sinus fractures, are relatively common facial fractures. Many agree on the general principles of frontal fracture management; however, the optimal methods of reduction are still controversial. In this article, we suggest a simple reduction method using a subbrow incision as a treatment for isolated anterior sinus fractures. METHODS: Between March 2011 and March 2014, 13 patients with isolated frontal sinus fractures were treated by open reduction and internal fixation through a subbrow incision. The subbrow incision line was designed to be precisely at the lower margin of the brow in order to obtain an inconspicuous scar. A periosteal incision was made at 3 mm above the superior orbital rim. The fracture site of the frontal bone was reduced, and bone fixation was performed using an absorbable plate and screws. RESULTS: Contour deformities were completely restored in all patients, and all patients were satisfied with the results. Scars were barely visible in the long-term follow-up. No complications related to the procedure, such as infection, uncontrolled sinus bleeding, hematoma, paresthesia, mucocele, or posterior wall and brain injury were observed. CONCLUSIONS: The subbrow approach allowed for an accurate reduction and internal fixation of the fractures in the anterior table of the frontal sinus by providing a direct visualization of the fracture. Considering the surgical success of the reduction and the rigid fixation, patient satisfaction, and aesthetic problems, this transcutaneous approach through a subbrow incision is concluded to be superior to the other reduction techniques used in the case of an anterior table frontal sinus fracture.
Brain Injuries ; Cicatrix ; Congenital Abnormalities ; Follow-Up Studies ; Fracture Fixation, Internal ; Frontal Bone ; Frontal Sinus* ; Hematoma ; Hemorrhage ; Humans ; Mucocele ; Orbit ; Paresthesia ; Patient Satisfaction ; Surgical Procedures, Minimally Invasive

Metformin, an oral hypoglycemic agent belonging to biguanide class, is widely used to treat type 2 diabetes mellitus, and several drug transporters such as organic cation transporters (OCTs), multidrug and toxin extrusion transporter (MATE), and plasma membrane monoamine transporter (PMAT) are thought to affect its disposition. We evaluated the role of PMAT genetic variations on the pharmacokinetic characteristics of metformin in a Korean population. In this retrospective study, 91 healthy subjects from four different metformin pharmacokinetic studies were analyzed; in each study, the subjects were administered two oral doses of metformin at intervals of 12 hours and dose-normalized pharmacokinetic parameters were compared between the subjects' genotypes. Subjects who had more than one allele of c.883-144A>G single nucleotide polymorphism (SNP) in PMAT gene (rs3889348) showed increased renal clearance of metformin compared to wild-type subjects (814.79 ± 391.73 vs. 619.90 ± 195.43 mL/min, p=0.003), whereas no differences in metformin exposure were observed between the PMAT variant subjects and wild-type subjects. Similarly, subjects with variant rs316019 SNP in OCT2 showed decreased renal clearance of metformin compared to wild-type subjects (586.01 ± 160.54 vs. 699.13 ± 291.40 mL/min, p=0.048). Other SNPs in PMAT and MATE1/2-K genes did not significantly affect metformin pharmacokinetics. In conclusion, the genetic variation of c.883-144A>G SNP in PMAT significantly affects the renal clearance of metformin in healthy Korean male subjects.
Alleles ; Cell Membrane ; Diabetes Mellitus, Type 2 ; Genetic Variation ; Genotype ; Healthy Volunteers ; Humans ; Male ; Metformin ; Pharmacokinetics ; Plasma ; Polymorphism, Single Nucleotide ; Retrospective Studies

Background: Reducing the total anticholinergic burden (AB) in older adults is recommended owing to the several peripheral and central adverse effects. This study aimed to identify the AB status of patients admitted to geriatric centers for assessing the influence of the pharmacist-involved multidisciplinary geriatric team care on reducing the AB. Methods: We retrospectively reviewed the medical records of 328 older patients hospitalized in geriatric centers from July 1, 2018 to June 30, 2019, who received comprehensive geriatric assessment and pharmaceutical interventions from a multidisciplinary geriatric team. We measured the total AB scores for the medications at the time of admission and upon hospital discharge using the Korean Anticholinergic Burden Scale (KABS). The pre-admission factors associated with high AB (KABS score ≥3) at the time of admission were identified. Results: The proportion of patients with high AB significantly decreased from 41.8% (136/328) at the time of admission to 25.0% (82/328) on discharge (p<0.001). The pre-admission AB of patients transferred from skilled nursing facilities (odds ratio[OR]: 2.85, 95% CI: 1.26- 3.75), taking more than 10 medications (OR: 3.70, 95% CI: 1.55-8.82), suffering from delirium (OR: 2.80, 95% CI: 1.04-7.50), or depression (OR: 2.78, 95% CI: 1.04-7.41) were significantly high. Antipsychotics were the most frequent classes of drugs that contributed to the total KABS score at the time of admission, followed by antihistamines. Conclusions This study demonstrated that the multidisciplinary teams for geriatric care are effective at reducing AB in older adults. The factors associated with high AB should be considered when targeting pharmaceutical care in geriatric individuals.

Freeman-Sheldon syndrome (FSS) is a rare distal arthrogryposis syndrome. There are few reports on the respiratory insufficiency of FSS. Additionally, there is no detailed information on pulmonary functional evaluation. A 17-year-old male patient with FSS developed respiratory failure, leading him to be admitted to hospital several times for evaluation and treatment. Of those times he was admitted, two were due to pneumonia. His pulmonary functions were indicative of a restrictive lung disease potentially caused by severe scoliosis. After a non-invasive ventilatorwas applied correctly to the patient, pulmonary hypertension was normalized. His pulmonary function has been maintained for 13 years. Since receiving proper respiratory care, which includes assisted coughing methods, the patient has not developed pneumonia. It is important to properly evaluate the pulmonary function of patients who have FSS and scoliosis to eliminate the risk of long-term respiratory complications.

Background: The coronavirus disease 2019 (COVID-19) pandemic is an emerging threat worldwide. It remains unclear how comorbidities affect the risk of infection and severity of COVID-19. Methods: This is a nationwide retrospective case-control study of 219,961 individuals, aged 18 years or older, whose medical costs for COVID-19 testing were claimed until May 15, 2020. COVID-19 diagnosis and infection severity were identified from reimbursement data using diagnosis codes and on the basis of respiratory support use, respectively. Odds ratios (ORs) were estimated using multiple logistic regression, after adjusting for age, sex, region, healthcare utilization, and insurance status. Results: The COVID-19 group (7,341 of 219,961) was young and had a high proportion of female. Overall, 13.0% (954 of 7,341) of the cases were severe. The severe COVID-19 group had older patients and a proportion of male ratio than did the non-severe group. Diabetes (odds ratio range [ORR], 1.206–1.254), osteoporosis (ORR, 1.128–1.157), rheumatoid arthritis (ORR, 1.207–1.244), substance use (ORR, 1.321–1.381), and schizophrenia (ORR, 1.614–1.721) showed significant association with COVID-19. In terms of severity, diabetes (OR, 1.247; 95% confidential interval, 1.009–1.543), hypertension (ORR, 1.245–1.317), chronic lower respiratory disease (ORR, 1.216–1.233), chronic renal failure, and end-stage renal disease (ORR, 2.052–2.178) were associated with severe COVID-19. Conclusion We identified several comorbidities associated with COVID-19. Health care workers should be more careful while diagnosing and treating COVID-19 when patients have the abovementioned comorbidities.