BACKGROUND: Earlier studies have reported conflicting results regarding long-term behavioral consequences after anesthesia during the fetal period. Previous studies also suggest several factors that may explain such conflicting data. Thus, we examined the influence of age and sex on long-term behavioral consequences after multiple sevoflurane exposures during the fetal period. METHODS: C57BL/6J pregnant mice received oxygen with or without sevoflurane for 2 hours at gestational day (GD) 14-16. Offspring mice were subjected to behavioral assays for general activity (open field test), learning, and memory (fear chamber test) at postnatal day 30–35. RESULTS: Multiple sevoflurane exposures at GD 14–16 caused significant changes during the fear chamber test in young female offspring mice. Such changes did not occur in young male offspring mice. However, general activity was not affected in both male and female mice. CONCLUSIONS: Multiple sevoflurane exposures in the second trimester of pregnancy affects learning and memory only in young female mice. Further studies focusing on diverse cognitive functions in an age-, sex-dependent manner may provide valuable insights regarding anesthesia-induced neurotoxicity.
Anesthesia ; Animals ; Cognition ; Female* ; Fetus ; Humans ; Learning ; Male ; Memory* ; Mice* ; Oxygen ; Pregnancy Trimester, Second ; Pregnancy*

Vancomycin is a widely used glycopeptide antibiotic that requires therapeutic drug monitoring (TDM) owing to its narrow therapeutic window. It is primarily eliminated by renal excretion; thus, estimating the renal function of a patient is vital in the TDM of vancomycin. In patients with Duchenne muscular dystrophy (DMD), it is difficult to estimate the glomerular filtration rate using the serum creatinine level owing to the pathophysiological nature of the disease. Here, we report a case of a patient in whom TDM of vancomycin was performed, and explore the appropriate methods for evaluating renal function in patients with DMD based on serum levels of creatinine and cystatin C.
Creatinine ; Cystatin C ; Drug Monitoring* ; Glomerular Filtration Rate ; Humans ; Muscular Dystrophy, Duchenne* ; Renal Elimination ; Vancomycin*

PURPOSE: To describe a patient who presented with central serous chorioretinopathy after 2 months of tadalafil administration without any other underlying disease or medication. CASE SUMMARY: A 49-year-old male patient was transferred from a local clinic with metamorphopsia and decreased visual acuity in the right eye. His visual acuity was 6/20 in the right eye and 18/20 in the left eye. The fundus examination showed a large serous detachment between the superior and inferior blood vessel arcades in the right retina. In his medical history, he used tadalafil three times a week for 2 months. His medication was then stopped, and a follow-up examination was scheduled. After 2 months, a fundus examination showed resolution of the subretinal fluid, and his corrected visual acuity recovered to 20/20. CONCLUSIONS: Tadalafil (Cialis®) is a phosphodiesterase (PDE)-5 inhibitor and predominantly prescribed for the treatment of erectile dysfunction. PDE–5 inhibitors may be potent vasodilators in the retina and choroid, and may induce choroidal vessel engorgement leading to leakage across the retinal pigment epithelium and accumulation of subretinal fluid in selected patients. When making a diagnosis as central serous chorioretinopathy, the physician should confirm the causative drugs that are easy to miss, by performing a thorough review of the patient's medical history and promptly terminating the causative drugs.
Blood Vessels ; Central Serous Chorioretinopathy ; Choroid ; Diagnosis ; Erectile Dysfunction ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Retina ; Retinal Pigment Epithelium ; Subretinal Fluid ; Tadalafil ; Vasodilator Agents ; Vision Disorders ; Visual Acuity

PURPOSE: We report a case of spontaneous recovery of an iris cyst with only tuberculosis medication and conservative eye drops when uveitis and angle closure occurred because of a cyst in a patient with peritoneal tuberculosis. CASE SUMMARY: A 49-year-old female who was diagnosed with iritis and treated with steroid eye drops visited our clinic because of decreased visual acuity 1 month prior. There were anterior chamber inflammation cells and an iris cyst completely obstructing the anterior chamber at 12 o'clock. At the time, the patient had been diagnosed with peritoneal tuberculosis in the Department of Internal Medicine and Gynecology and had been treated with surgery and medication. The patient had no past history of glaucoma, but when the iris cyst developed, the intraocular pressure increased to 29 mmHg and anterior inflammatory cells were seen in the range of +1 to +2. The primary lesion of tuberculosis improved and the iris cyst disappeared with treatments involving medication for tuberculosis, steroid eye drops, and glaucoma eye drops, without invasive treatments such as alcohol curettage, laser treatment, or cyst resection. CONCLUSIONS: If an iris cyst is a new lesion of the eye, it is necessary to identify the pattern and cause of the iris cyst first, and if a secondary benign iris cyst is suspected, the primary treatment of the causative disease is necessary rather than prompt invasive treatment.
Anterior Chamber ; Curettage ; Female ; Glaucoma ; Gynecology ; Humans ; Inflammation ; Internal Medicine ; Intraocular Pressure ; Iris ; Iritis ; Middle Aged ; Ophthalmic Solutions ; Peritonitis, Tuberculous ; Tuberculosis ; Uveitis ; Visual Acuity

Cancer chemotherapy often triggers peripheral neuropathy in patients, leading to neuropathic pain in the extremities. While previous research has explored various nerve stimulation to alleviate chemotherapy-induced peripheral neuropathy (CIPN), evidence on the effectiveness of noninvasive auricular vagus nerve stimulation (aVNS) remains uncertain. This study aimed to investigate the efficacy of non-invasive aVNS in relieving CIPN pain. To induce CIPN in experimental animals, oxaliplatin was intraperitoneally administered to rats (6 mg/kg). Mechanical and cold allodynia, the representative symptoms of neuropathic pain, were evaluated using the von Frey test and acetone test, respectively. The CIPN animals were randomly assigned to groups and treated with aVNS (5 V, square wave) at different frequencies (2, 20, or 100 Hz) for 20 minutes. Results revealed that 20 Hz aVNS exhibited the most pronounced analgesic effect, while 2 or 100 Hz aVNS exhibited weak effects. Immunohistochemistry analysis demonstrated increased c-Fos expression in the locus coeruleus (LC) in the brain of CIPN rats treated with aVNS compared to sham treatment. To elucidate the analgesic mechanisms involving the adrenergic descending pathway, α 1 -, α 2 -, or β-adrenergic receptor antagonists were administered to the spinal cord before 20 Hz aVNS. Only the β-adrenergic receptor antagonist, propranolol, blocked the analgesic effect of aVNS.These findings suggest that 20 Hz aVNS may effectively alleviate CIPN pain through β-adrenergic receptor activation.

There are several hurdles to overcome before implementing pharmacogenomics (PGx) in precision medicine. One of the hurdles is unawareness of PGx by clinicians due to insufficient pharmacogenomic information on drug labels. Therefore, it might be important to implement PGx that reflects pharmacogenomic information on drug labels, standard of prescription for clinicians. This study aimed to evaluate the level at which PGx was being used in clinical practice by comparing the Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group guidelines and drug labels of the US Food and Drug Administration (FDA) and the Korea Ministry of Food and Drug Safety (MFDS). Two PGx guidelines and drugs labels were scrutinized, and the concordance of the pharmacogenomic information between guidelines and drug labels was confirmed. The concordance of the label between FDA and MFDS was analyzed. In FDA labels, the number of concordant drug with guidelines was 24, while 13 drugs were concordant with MFDS labels. The number of drugs categorized as contraindication, change dose, and biomarker testing required was 7, 12 and 12 for the FDA and 8, 5 and 4 for the MFDS, respectively. The pharmacogenomic information of 9 drugs approved by both FDA and MFDS was identical. In conclusion, pharmacogenomic information on clinical implementation guidelines was limited on both FDA and MFDS labels because of various reasons including the characteristics of the guidelines and the drug labels. Therefore, more effort from pharmaceutical companies, academia and regulatory affairs needs to be made to implement pharmacogenomic information on drug labels.

There are several hurdles to overcome before implementing pharmacogenomics (PGx) in precision medicine. One of the hurdles is unawareness of PGx by clinicians due to insufficient pharmacogenomic information on drug labels. Therefore, it might be important to implement PGx that reflects pharmacogenomic information on drug labels, standard of prescription for clinicians. This study aimed to evaluate the level at which PGx was being used in clinical practice by comparing the Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group guidelines and drug labels of the US Food and Drug Administration (FDA) and the Korea Ministry of Food and Drug Safety (MFDS). Two PGx guidelines and drugs labels were scrutinized, and the concordance of the pharmacogenomic information between guidelines and drug labels was confirmed. The concordance of the label between FDA and MFDS was analyzed. In FDA labels, the number of concordant drug with guidelines was 24, while 13 drugs were concordant with MFDS labels. The number of drugs categorized as contraindication, change dose, and biomarker testing required was 7, 12 and 12 for the FDA and 8, 5 and 4 for the MFDS, respectively. The pharmacogenomic information of 9 drugs approved by both FDA and MFDS was identical. In conclusion, pharmacogenomic information on clinical implementation guidelines was limited on both FDA and MFDS labels because of various reasons including the characteristics of the guidelines and the drug labels. Therefore, more effort from pharmaceutical companies, academia and regulatory affairs needs to be made to implement pharmacogenomic information on drug labels.

An extended-release (ER) fixed-dose combination (FDC) of tramadol 37.5 mg/acetaminophen 325 mg was developed due to the demand for varying dosages. This study aimed to evaluate the pharmacokinetics (PKs) for two tablets of the new developed tramadol 37.5 mg/acetaminophen 325 mg ER FDC (DW-0920, Wontran Semi ER®) as test formulation compared to one tablet of the tramadol 75 mg/acetaminophen 650 mg ER FDC (DW-0919, Wontran ER®) as reference formulation. A randomized, open-label, 2-way crossover study was conducted in 30 healthy subjects. Subjects were orally administered one of 2 formulations followed by an alternate formulation with a 7-day washout period. Blood samples were collected up to 36 hours post-dose. Plasma concentrations of tramadol and acetaminophen were determined using a validated high-performance liquid chromatography with tandem mass spectrometric method. The geometric mean ratios (GMRs) and their 90% confidence intervals (90% CIs) of test formulation to reference formulation were calculated for the maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve from zero to the last measurable time point (AUClast). The PK profiles of 2 formulations were comparable. The GMRs (90% CI) of Cmax and AUClast for tramadol were 1.086 (1.047–1.127) and 1.008 (0.975–1.042), respectively. The corresponding values for acetaminophen were 0.956 (0.897–1.019) and 0.986 (0.961–1.011), respectively. All the values were within the bioequivalence range of 0.80–1.25. Two tablets of DW-0920 were comparable to one tablet of DW-0919. The DW-0920 may be used for optimal pharmacotherapy for pain control with a lower dose.

Alpha-lipoic acid, a physiological form of thioctic acid, is a strong antioxidant that relieves diabetic neuropathic symptoms. R(+)-α-lipoic acid shows superior antioxidative effects to its racemate. We compared the pharmacokinetics (PKs) and tolerability of R(+)- and S(-)-α-lipoic acid after a single oral dose of R(+)-α-lipoic acid, Dexid®, and its racemate, thioctic acid in healthy male subjects. We used an open-label, randomized, single-dose, three-treatment, parallel study design to compare the PK exposure of the active form, R(+)-α-lipoic acid. Thirty subjects completed the study with no clinically relevant safety issues. The peak concentrations (C(max), mean±SD) of R(+)-α-lipoic acid after doses of R(+)-α-lipoic acid 200 mg, 300 mg and thioctic acid 600 mg were 4186.8±1956.7, 6985.6±3775.8 and 6498.4±3575.6 µg/L, respectively, and the areas under the plasma concentration-time curve from 0 to the last measurable concentration (AUC(last)) were 1893.6±759.4, 3575.2±1149.2 and 3790.0±1623.0 µg·h⁻¹·L⁻¹, respectively. The geometric mean ratio and 90% confidence intervals of R(+)-α-lipoic acid 200 mg to thioctic acid 600 mg for the C(max) and AUC(last) were 0.71 (0.43–1.15) and 0.51 (0.37–0.70), respectively. The corresponding R(+)-α-lipoic acid 300 mg to thioctic acid 600 mg values were 1.11 (0.68-1.80) and 0.97 (0.71-1.34), respectively. In conclusion, R(+)-α-lipoic acid 300 mg showed PK characteristics similar to those of thioctic acid 600 mg and both formulations were well tolerated.
Humans ; Male* ; Pharmacokinetics ; Plasma ; Thioctic Acid*

Mycobacterium avium complex (MAC) is an opportunistic bacterium that primarily infects acquired immune deficiency syndrome (AIDS) patients with low CD4+ T cell counts; however, peritonitis caused by MAC in AIDS patients is rare. Here, we report the first case of peritonitis caused by MAC in AIDS patients in Korea. A 41-year-old female with poor adherence to antiretroviral therapy was admitted to hospital with nonspecific symptoms; an abdominal computed tomography (CT) scan revealed substantial ascites, splenomegaly, and lymphadenopathy. Based on the CT scan and ascitic fluid cultures, MAC peritonitis was diagnosed. In addition to antiretroviral therapy, clarithromycin, rifabutin, and ethambutol were administered to treat the MAC infection, and the patient's symptoms improved.
Acquired Immunodeficiency Syndrome* ; Adult ; Ascites ; Ascitic Fluid ; Cell Count ; Clarithromycin ; Ethambutol ; Female ; HIV ; Humans ; Korea ; Lymphatic Diseases ; Mycobacterium avium Complex* ; Mycobacterium avium* ; Mycobacterium* ; Peritonitis ; Rifabutin ; Splenomegaly ; Tomography, X-Ray Computed