A simple, rapid, and reliable UPLC-MS/MS method was developed and validated for the determination of tadalafil in human plasma. The plasma samples were deproteinized with acetonitrile. Chromatographic separation was performed on a Shiseido C18 (100 × 2.1 mm, 2.7 µm) column with isocratic elution using 2.0 mM ammonium acetate and acetonitrile (55:45, v/v) with 0.1% formic acid at a flow rate of 0.7 mL/min. The total run time was 1 min per sample. The quantitative analysis was performed using multiple reaction monitoring at transition of m/z 390.4 → 268.3 for tadalafil and m/z 475.3 → 283.3 for sildenafil as an internal standard. The method was fully validated over a concentration range of 5–1,000 ng/mL with a lower quantification limit of 5 ng/mL. Intra- and inter-day precision (relative standard deviation, %RSD) were within 8.4% and accuracy (relative error, %RE) was lower than -3.2%. The developed and validated method was successfully applied to a pharmacokinetic study of tadalafil (20 mg) in Korean healthy male subjects (n = 12).
Ammonium Compounds ; Humans* ; Male ; Methods* ; Pharmacokinetics ; Plasma* ; Sildenafil Citrate ; Tadalafil*

BACKGROUND: Paraplegia is a devastating complication following operations on the thoracoabdominal aorta. We investigated whether histidine-tryptophan-ketoglutarate (HTK) solution could reduce the extent of ischemia/reperfusion (IR) spinal cord injuries in a rat model using a direct delivery method. METHODS: Twenty-four Sprague-Dawley male rats were randomly divided into four groups. The sham group (n=6) underwent a sham operation, the IR group (n=6) underwent only an aortic occlusion, the saline infusion group (saline group, n=6) underwent an aortic occlusion and direct infusion of cold saline into the occluded aortic segment, and the HTK infusion group (HTK group, n=6) underwent an aortic occlusion and direct infusion of cold HTK solution into the occluded aortic segment. An IR spinal cord injury was induced by transabdominal clamping of the aorta distally to the left renal artery and proximally to the aortic bifurcation for 60 minutes. A neurological evaluation of locomotor function was performed using the modified Tarlov score after 48 hours of reperfusion. The spinal cord was harvested for histopathological and immunohistochemical examinations. RESULTS: The spinal cord IR model using direct drug delivery in rats was highly reproducible. The Tarlov score was 4.0 in the sham group, 1.17±0.75 in the IR group, 1.33±1.03 in the saline group, and 2.67±0.81 in the HTK group (p=0.04). The histopathological analysis of the HTK group showed reduced neuronal cell death. CONCLUSION: Direct infusion of cold HTK solution into the occluded aortic segment may reduce the extent of spinal cord injuries in an IR model in rats.
Animals ; Aorta ; Cell Death ; Constriction ; Humans ; Male ; Methods ; Models, Animal ; Neurons ; Neuroprotective Agents* ; Paraplegia ; Rats ; Rats, Sprague-Dawley ; Renal Artery ; Reperfusion ; Reperfusion Injury ; Spinal Cord Injuries* ; Spinal Cord*

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) pulmonary wedge resection has emerged as the standard treatment for primary spontaneous pneumothorax. Recently, single-port VATS has been introduced and is now widely performed. This study aimed to evaluate the outcomes of the Tower crane technique as novel technique using a 15-mm trocar and anchoring suture in primary spontaneous pneumothorax. METHODS: Patients who underwent single-port VATS wedge resection in Chungnam National University Hospital from April 2012 to March 2014 were enrolled. The medical records of the enrolled patients were reviewed retrospectively. RESULTS: A total of 1,251 patients were diagnosed with pneumothorax during this period, 270 of whom underwent VATS wedge resection. Fifty-two of those operations were single-port VATS wedge resections for primary spontaneous pneumothorax performed by a single surgeon. The median age of the patients was 19.3±11.5 years old, and 43 of the patients were male. The median duration of chest tube drainage following the operation was 2.3±1.3 days, and mean postoperative hospital stay was 3.2±1.3 days. Prolonged air leakage for more than three days following the operation was observed in one patient. The mean duration of follow-up was 18.7±6.1 months, with a recurrence rate of 3.8%. CONCLUSION: The tower crane technique with a 15-mm trocar may be a promising treatment modality for patients presenting with primary spontaneous pneumothorax.
Chest Tubes ; Chungcheongnam-do ; Drainage ; Follow-Up Studies ; Humans ; Length of Stay ; Male ; Medical Records ; Pneumothorax* ; Recurrence ; Retrospective Studies ; Surgical Instruments* ; Sutures ; Thoracic Surgery, Video-Assisted

BACKGROUND/AIMS: Helicobacter pylori is a distinctive pathogen that lives in the gastric mucosa and is a well known risk factor of gastric adenocarcinoma. Iron deficiency aggravates the development of H. pylori-induced premalignant and malignant lesions in a cagA-dependent manner, enhancing H. pylori virulence. The aim of this study was to identify the relationship between iron deficiency and H. pylori eradication rates. MATERIALS AND METHODS: Participants who received 7 days of first-line triple therapy with serum iron level measured in parallel were retrospectively investigated between 2005 and 2014. H. pylori eradication was confirmed by the rapid urease test or 13C-urea breath test at least 4 weeks after completion of triple therapy. Iron deficiency was defined as either a serum iron level less than 50 µg/dL or a serum ferritin level less than 12 ng/mL. RESULTS: A total of 194 patients received 7 days of first-line triple therapy along with parallel serum iron level measurements over the 10-year period. The mean average age was 53.3 years (range, 21~86 years), and 135 patients (69.6%) were male. The overall H. pylori eradication rate was 83.5%. Proportions of eradication success with ferritin level less than 12 ng/mL and iron less than 50 µg/dL were 90.5% and 88.6%, respectively. However, there was no statistical difference in eradication rates according to iron deficiency. CONCLUSIONS: Iron deficiency might not be related with H. pylori eradication rates in this study. Further large-scale studies are needed to confirm this result.
Adenocarcinoma ; Breath Tests ; Disease Eradication ; Ferritins ; Gastric Mucosa ; Helicobacter pylori* ; Helicobacter* ; Humans ; Iron* ; Male ; Retrospective Studies ; Risk Factors ; Urease ; Virulence

BACKGROUND: Psoriasis is associated with increased risk of cardiovascular morbidities, especially in severe cases. Severity of the disease has been known to be associated with higher prevalence of these risk factors. However, in the absence of robust measurements, studies to date relied mostly on treatment spectrum as a proxy for the severity. OBJECTIVE: To evaluate the relationship between psoriasis area and severity index (PASI) and cardiovascular risk factors in Korean patients. METHODS: Presence of diabetes mellitus (DM), hypertension, smoking history was surveyed through questionnaires and serum lipid profile analysis were done after fasting overnight. The severity of psoriasis was assessed using PASI scores: mild, <10; moderate to severe, ≥10. Cardiovascular risk factors such as smoking, hypertension, diabetes and dyslipidemia were compared between the mild group and moderate to severe group. The prevalence of diabetes and hypertension was compared among these two groups of psoriasis patients and the general population based control; age and gender were matched among three groups accordingly prior to analysis. RESULTS: A total of 256 patients with plaque type psoriasis were included. Between mild group and moderate to severe group, significant differences of cardiovascular risk factors including lipid profile were not discovered except in triglyceride level. Comparing to general population, prevalence of diabetes was found significantly higher in psoriasis patients while that of hypertension was similar. CONCLUSION: Our results suggest that among cardiovascular risks, presence of DM and triglyceride level seem to be associated with the presence of psoriasis in Korean psoriasis patients, while other factors may not contribute meaningfully.
Diabetes Mellitus ; Dyslipidemias ; Fasting ; Humans ; Hypertension ; Prevalence ; Proxy ; Psoriasis* ; Risk Factors* ; Smoke ; Smoking ; Triglycerides

BACKGROUND AND OBJECTIVES: We compared the efficacy and safety of valsartan and rosuvastatin combination therapy with each treatment alone in hypercholesterolemic hypertensive patients. SUBJECTS AND METHODS: Patients who met inclusion criteria were randomized to receive 1 of the following 2-month drug regimens: valsartan 160 mg plus rosuvastatin 20 mg, valsartan 160 mg plus placebo, or rosuvastatin 20 mg plus placebo. The primary efficacy variables were change in sitting diastolic blood pressure (sitDBP) and sitting systolic blood pressure (sitSBP), and percentage change in low-density lipoprotein-cholesterol (LDL-C) in the combination, valsartan, and rosuvastatin groups. Adverse events (AEs) during the study were analyzed. RESULTS: A total of 354 patients were screened and 123 of them were finally randomized. Changes of sitDBP by least squares mean (LSM) were -11.1, -7.2, and -3.6 mm Hg, respectively, and was greater in the combination, as compared to both valsartan (p=0.02) and rosuvastatin (p<0.001). Changes of sitSBP by LSM were -13.2, -10.8, and -4.9 mm Hg, and was greater in the combination, as compared to rosuvastatin (p=0.006) and not valsartan (p=0.42). Percentage changes of LDL-C by LSM were -52, -4, and -47% in each group, and was greater in the combination, as compared to valsartan (p<0.001), similar to rosuvastatin (p=0.16). Most AEs were mild and resolved by the end of the study. CONCLUSION: Combination treatment with valsartan and rosuvastatin exhibited an additive blood pressure-lowering effect with acceptable tolerability, as compared to valsartan monotherapy. Its lipid lowering effect was similar to rosuvatatin monotherapy.
Blood Pressure ; Drug Therapy, Combination ; Humans ; Least-Squares Analysis ; Rosuvastatin Calcium ; Valsartan

Previous studies in Holstein have shown 35% to 51.8% heritability in milk production traits, such as milk yield, fat, and protein, using pedigree data. Other studies in complex human traits could be captured by common single-nucleotide polymorphisms (SNPs), and their genetic variations, attributed to chromosomes, are in proportion to their length. Using genome-wide estimation and partitioning approaches, we analyzed three quantitative Holstein traits relevant to milk production in Korean Holstein data harvested from 462 individuals genotyped for 54,609 SNPs. For all three traits (milk yield, fat, and protein), we estimated a nominally significant (p = 0.1) proportion of variance explained by all SNPs on the Illumina BovineSNP50 Beadchip (h(2)(G)). These common SNPs explained approximately most of the narrow-sense heritability. Longer genomic regions tended to provide more phenotypic variation information, with a correlation of 0.46~0.53 between the estimate of variance explained by individual chromosomes and their physical length. These results suggested that polygenicity was ubiquitous for Holstein milk production traits. These results will expand our knowledge on recent animal breeding, such as genomic selection in Holstein.
Animals ; Breeding* ; Genetic Variation ; Humans ; Milk ; Pedigree ; Polymorphism, Single Nucleotide*

In this article, on page 230, Fig. 2A needs to be corrected.

No abstract available.
Carcinoma, Adenoid Cystic* ; Humans ; Knee* ; Male

BACKGROUND: Kruppel-like factor 4 (KLF4) is a transcription factor that regulates a diverse array of cellular processes, including development, differentiation, proliferation, and apoptosis. Although its function in keratinocytes has been widely studied, its exact role in psoriasis has not been elucidated. OBJECTIVE: We designed this study to investigate epidermal expression levels of KLF4 and the change in KLF4 expression after treatment in patients with psoriasis. METHODS: We compared the expression levels of KLF4 in the basal, suprabasal, and superficial epidermal layers, in psoriatic lesional, non-lesional, and normal skin, using an immunoreactivity intensity distribution index (IRIDI). In addition, we measured the change in KLF4 expression on the basis of the IRIDI and by reverse transcription polymerase chain reaction (RT-PCR) analysis after treatment. RESULTS: The combined IRIDI scores in psoriatic lesional skin were significantly higher than the scores in both non-lesional and normal skin. The psoriatic epidermis, particularly the suprabasal layer, showed a significantly increased IRIDI score compared to that of non-lesional and normal skin, which was significantly decreased after treatment. RT-PCR analysis exhibited a slight increase in KLF4 mRNA expression level after treatment; however, this increase was not significant. CONCLUSION: These data indicate that KLF4 could regulate epidermal proliferation and differentiation. Moreover, we believe that KLF4 may play an important role in the physiological reaction to counteract abnormal differentiation and proliferation of keratinocytes.
Apoptosis ; Epidermis ; Humans ; Keratinocytes ; Polymerase Chain Reaction ; Psoriasis* ; Reverse Transcription ; RNA, Messenger ; Skin ; Transcription Factors