Epigallocatechin-3-gallate (EGCG) is a green tea polyphenol exerting potent anti-oxidant and anti-inflammatory effects by inhibiting signaling and gene expression. The objective of the study was to evaluate the effect of EGCG on interleukin (IL)-1 receptor antagonist knockout (IL-1RaKO) autoimmune arthritis models. IL-1RaKO arthritis models were injected intraperitoneally with EGCG three times per week after the first immunization. EGCG decreased the arthritis index and showed protective effects against joint destruction in the IL-1RaKO arthritis models. The expression of pro-inflammatory cytokines, oxidative stress proteins, and p-STAT3 (Y705) and p-STAT3 (S727), mTOR and HIF-1α were significantly lower in mice treated with EGCG. EGCG reduced osteoclast markers in vivo and in vitro along with anti-osteoclastic activity was observed in EGCG-treated IL-1RaKO mice. The proportion of Foxp3+ Treg cells increased in the spleens of mice treated with EGCG, whereas the proportion of Th17 cells reduced. In vitro, p-STAT3 (Y705) and p-STAT3 (S727), HIF1α and glycolytic pathway molecules were decreased by EGCG. EGCG suppressed the activation of mTOR and subsequently HIF-1α, which is considered as a metabolic check point of Th17/Treg differentiation supporting the therapeutic potential of EGCG in autoimmune arthritis.
Recognition of microbes is important to trigger the innate immune system. Mycolic acid (MA) is a component of the cell walls of mycobacteria such as Mycobacterium bovis Bacillus Calmette-Guerin. MA has immunogenic properties, which may modulate the innate and adaptive immune response. This study aimed to investigate whether a novel synthetic MA (sMA) inhibits allergic inflammatory responses in a mouse model of asthma.
BALB/c mice were injected intraperitoneally with sMA followed by sensitization and challenge with ovalbumin (OVA). Mice were examined for bronchial hyperresponsiveness (BHR), the influx of inflammatory cells into the lung tissues, histopathological changes in the lungs and CD4+CD25+Foxp3+ T cells in the spleen, and examined the response after the depleting regulatory T cells (Tregs) with an anti-CD25mAb.
Treatment of mice with sMA suppressed the asthmatic response, including BHR, bronchoalveolar inflammation, and pulmonary eosinophilic inflammation. Anti-CD25mAb treatment abrogated the suppressive effects of sMA in this mouse model of asthma and totally depleted CD4+CD25+Foxp3+ T cells in the spleen.
sMA attenuated allergic inflammation in a mouse model of asthma, which might be related with CD4+CD25+Foxp3+ T cell.
Mycolic acid; asthma; allergic inflammation; regulatory T cells; mice
Helicobacter pylori (H. pylori) is a major etiological factor in the development of gastric cancer. Large-scale epidemiological studies have confirmed the strong association between H. pylori infection and both cancer development and progression. Interleukin-8 (IL-8) is overexpressed in gastric mucosa exposed to H. pylori. The expression of IL-8 directly correlates with a poor prognosis in gastric cancer. IL-8 is multifunctional. In addition to its potent chemotactic activity, it can induce proliferation and migration of cancer cells. In this review, we focus on recent insights into the mechanisms of IL-8 signaling associated with gastric cancer. The relationship between IL-8 and H. pylori is discussed. We also summarize the current therapeutics against IL-8 in gastric cancer.
Helicobacter pylori; Interleukin-8; Signals; Gastric cancer; Therapeutics
There is little consensus on how to optimally reconstruct the posterior cruciate ligament (PCL) and the natural history of injured PCL is also unclear. The graft material (autograft vs. allograft), the type of tibial fixation (tibial inlay vs. transtibial tunnel), the femoral tunnel position within the femoral footprint (isometric, central, or eccentric), and the number of bundles in the reconstruction (1 bundle vs. 2 bundles) are among the many decisions that a surgeon must make in a PCL reconstruction. In addition, there is a paucity of information on rehabilitation after reconstruction of the PCL and posterolateral structures. This article focused on the conflicting issues regarding the PCL, and the scientific rationales behind some critical points are discussed.
Knee; Posterior cruciate ligament; Biomechanics; Outcome; Rehabilitation
The purpose of the present study was to compare the clinical results of 3 posterior cruciate ligament reconstruction techniques according to the time from injury to surgery and remnant PCL status and to evaluate the efficiency of each technique.
The records of 89 patients who underwent primary PCL reconstructions with a posterolateral corner sling were analyzed retrospectively. Thirty-four patients were treated by anterolateral bundle (ALB) reconstruction with preservation of the remnant PCL using a transtibial tunnel technique in the acute and subacute stages of injury (group 1). Forty patients were treated with remnant PCL tensioning and an ALB reconstruction using the modified inlay technique in the chronic stage (group 2), and fifteen patients were treated with double-bundle reconstruction using the modified inlay technique (group 3). The double-bundle reconstruction was performed if there was a very weak or no PCL remnant.
The mean side-to-side differences in posterior tibial translation on the stress radiographs were reduced from 10.1 ± 2.5 mm in group 1, 10.6 ± 2.4 mm in group 2, and 12.8 ± 3.2 mm in group 3 preoperatively to 2.3 ± 1.4 mm in group 1, 2.3 ± 1.5 mm in group 2, and 4.0 ± 2.5 mm in group 3 at the last follow-up (p < 0.001, p < 0.001, and p < 0.001, respectively). Statistical analyses revealed that group 1 and group 2 were similar in terms of side-to-side difference changes in posterior tibial translation on the stress radiographs; however, group 3 was inferior to group 1 and group 2 at the last follow-up (p = 0.022). The clinical results were not significantly different among the three groups.
Excellent posterior stability and good clinical results were achieved with ALB reconstruction preserving the injured remnant PCL in the acute and subacute stages and remnant PCL tensioning with ALB reconstruction in the chronic stage. The PCL injuries could be surgically corrected with different techniques depending on both the remnant PCL status and the interval between the knee trauma and operation.
Posterior cruciate ligament; Posterolateral corner reconstruction; Modified inlay; Transtibial tunnel; Double-bundle
This study was to evaluate the phenolic content and composition of Carthamus tinctorius L. seed extract (CSE) and to further assess its antioxidant and anti-adipogenic activities using various radical scavenging systems and 3T3-L1 cells. Our results show that the total phenolic and flavonoid contents of CSE were 126.0 ± 2.4 mg GAE/g and 62.2 ± 1.9 mg QE/g, respectively. The major phenolic compounds in CSE was (−)-epigallocatechin (109.62 mg/g), with a 4-hydroxy benzhydrazide derivative and gallocatechin present at 18.28 mg/g and 17.02 mg/g, respectively. CSE exhibited remarkable radical scavenging activities, FRAP (ferric reducing antioxidant power) and reducing power in a dose-dependent manner. Moreover, the oxygen radical absorbance capacity (ORAC) value of CSE (0.1 mg/mL) was 62.9 ± 4.7 μM TE (trolox equivalent)/g. During adipogenesis, CSE significantly inhibited fat accumulation in 3T3-L1 cells compared with control cells. Overall, these results indicate that CSE might be a valuable source of bioactive compounds that impart functional food and natural antioxidant properties.
antioxidant activity; phenolic compound; Carthamus tinctorius L. seed; 3T3-L1 adipocyte; hot-water extract
Red Liriope platyphylla (RLP) has been manufactured from Liriope platyphylla (L. platyphylla, LP) roots using steaming process and investigated as a curative agent for treatment of diabetes, obesity and neurodegenerative disorders. To examine the precautionary effects of aqueous extract RLP (AEtRLP) on the preclinical stages of Alzheimer's Disease (AD), alterations of the key factors influencing AD were investigated in Tg2576 mice after AEtRLP7 treatment for 4 months. Aβ-42 peptides level was significantly decreased in the brain of AEtRLP7-treated Tg2576 mice compared to vehicle-treated Tg2576 mice, although significant differences on improving behavioral defects were not observed in the same group. The concentration of nerve growth factor (NGF) in serum was also higher in AEtRLP7-treated Tg2576 mice than vehicle-treated Tg2576 mice. However, the phosphorylation of TrkA and Erk among the downstream effectors of the high affinity NGF receptor was significantly lower in AEtRLP7-treated Tg2576 mice. A similar pattern was observed in the expression level of downstream effectors within low affinity NGF receptor. Overall, these results suggest that AEtRLP7 can contribute to preventing the production and deposition of Aβ-42 peptides during the early progression stage of AD in the brain of Tg2576 mice through increased NGF secretion.
Red Liriope platyphylla; NGF; NGF signaling pathway; Aβ-42
It has been reported that working and learning efficiency might be increased through artificially controlling the color temperature and brightness of light. However, the neurological bases of these outcomes are not well established. Our study was designed to observe whether electroencephalogram (EEG) alpha frequency, as a candidate biological marker, demonstrates significant changes in response to alterations of specific light parameters.
Thirty-two healthy subjects performed cognitive tasks under four different polychromatic light conditions: a combination of two different levels of color temperature (2766K vs. 5918K) and brightness (300 lux vs. 600 lux). Spectrum analyses were performed on alpha frequency.
Subjects reported that they felt more pleasant in bright conditions and more relaxed in warm color temperature conditions. Our findings indicate that alpha power increases in warm, low-light and cool, high-light conditions, and there is a significant interaction between color temperature and brightness.
EEGs might serve as a useful biological marker for further research related to the effects of polychromatic light on cognitive function.
Polychromatic light; Color temperature; Brightness; Electroencephalogram; Alpha frequency
Bamboo shavings (Bambusae Caulis in Taeniam, BCT) are widely used as a traditional Chinese medicine to control hypertension and cardiovascular disease, and to alleviate fever, vomiting, and diarrhea. It has been demonstrated that BCT reduces ovalbumin-induced airway inflammation by regulating pro-inflammatory cytokines, and decreases tumor growth in tumor-bearing mice. However, the effects of BCT on the metastatic potential of malignant cancer cells and the detailed mechanism of its anti-metastatic activity have not been examined previously. In this study, we investigated whether an aqueous extract of BCT (AE-BCT) reduces the metastatic potential of HT1080 cells, and elucidated the underlying anti-metastatic mechanism. In addition, we examined whether AE-BCT administration inhibits pulmonary metastasis of intravenously injected B16F10 cells in C57BL/6J mice. AE-BCT (50–250 µg/ml) dose-dependently suppressed colony-forming activity under anchorage-dependent and -independent growth conditions. Pretreatment with AE-BCT efficiently inhibited cell migration, invasion, and adhesion. AE-BCT also dramatically suppressed PMA-induced MMP-9 activity and expression by blocking NF-κB activation and ERK phosphorylation. Production of intracellular ROS, a key regulator of NF-κB-induced MMP-9 activity, was almost completely blocked by pretreatment with AE-BCT. Furthermore, daily oral administration of AE-BCT at doses of 50 and 100 mg/kg efficiently inhibited lung metastasis of B16F10 cells injected into the tail veins of C57BL/6J mice with no systemic toxicity. These results demonstrate that AE-BCT significantly reduced the metastatic activity of highly malignant cancer cells by suppressing MMP-9 activity via inhibition of ROS-mediated NF-κB activation. These results indicate that AE-BCT may be a safe natural product for treatment of metastatic cancer.
Atherosclerosis is a chronic and progressive inflammatory disease. Novel anti-inflammatory therapies may have promise as treatment strategies for cardiovascular risk reduction. Rosemary (Rosemarinus officinalis L.) has been used in folk medicine to treat headaches, epilepsy, poor circulation, and many other ailments. It was found that rosemary could act as a stimulant and mild analgesic and could reduce inflammation. However, the mechanisms underlying the anti-inflammatory and antiatherosclerotic effects of rosemary need more study. This study investigated effects of the rosemary components, carnosic acid (CA), and carnosol (CAR), on cell migration. Monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) were determined by Western blot and gelatin zymography, respectively, in RAW 264.7 macrophages and vascular smooth muscle cells (VSMCs). VSMC migration was assessed by a Matrigel migration assay. Active compounds of rosemary extracts were also analyzed using a reversed-phase high-performance liquid chromatography. MMP-9 and MCP-1 activities were markedly diminished with methanol extract (RM), n-hexane fraction (RH), and CA in RAW 264.7 cells. RM, RH, CA, and CAR suppressed tumor necrosis factor-alpha–induced VSMC migration by inhibiting MMP-9 expression. Chromatograms of RM- and RH-containing CA and CAR revealed higher CA contents of RM (9.4%, 93.85 μg/mg dry wt.) and, especially, RH (18.4%, 184.00 μg/mg dry wt.), which were appreciably elevated compared with the similar CAR content in RM and RH (3.7%, 37.30 μg/mg dry wt.; and 2.5%, 25.05 μg/mg dry wt., respectively). Rosemary, especially its CA component, has potential antiatherosclerosis effects related to cell migration.
Rosemarinus officinalis L.; rosemary; matrix metalloproteinase-9 (MMP-9); monocyte chemoattractant protein-1 (MCP-1); migration; RAW 264.7 macrophages; vascular smooth muscle cell
Previous studies suggest that the concentration of 25-hydroxyvitamin D [25(OH)D] in cord blood may show an inverse association with respiratory tract infections (RTI) during childhood. The aim of the present study was to examine the influence of 25(OH)D concentrations in cord blood on infant RTI in a Korean birth cohort.
The levels of 25(OH)D in cord blood obtained from 525 Korean newborns in the prospective COhort for Childhood Origin of Asthma and allergic diseases were examined. The primary outcome variable of interest was the prevalence of RTI at 6-month follow-up, as diagnosed by pediatricians and pediatric allergy and pulmonology specialists. RTI included acute nasopharyngitis, rhinosinusitis, otitis media, croup, tracheobronchitis, bronchiolitis, and pneumonia.
The median concentration of 25(OH)D in cord blood was 32.0 nmol/L (interquartile range, 21.4 to 53.2). One hundred and eighty neonates (34.3%) showed 25(OH)D concentrations less than 25.0 nmol/L, 292 (55.6%) showed 25(OH)D concentrations of 25.0-74.9 nmol/L, and 53 (10.1%) showed concentrations of ≥75.0 nmol/L. Adjusting for the season of birth, multivitamin intake during pregnancy, and exposure to passive smoking during pregnancy, 25(OH)D concentrations showed an inverse association with the risk of acquiring acute nasopharyngitis by 6 months of age (P for trend=0.0004).
The results show that 89.9% of healthy newborns in Korea are born with vitamin D insufficiency or deficiency (55.6% and 34.3%, respectively). Cord blood vitamin D insufficiency or deficiency in healthy neonates is associated with an increased risk of acute nasopharyngitis by 6 months of age. More time spent outdoors and more intensified vitamin D supplementation for pregnant women may be needed to prevent the onset of acute nasopharyngitis in infants.
Cohort studies; Infant; Respiratory tract infections; Umbilical cord blood; Vitamin D
The major cause of death in prostate cancer (PCa) cases is due to distant metastatic lesions, with the bone being the most prevalent site for secondary colonization. Utilization of small molecule inhibitors to treat bone metastatic PCa have had limited success either as monotherapies or in combination with other chemotherapeutics due to intolerable toxicities. In the current study, we developed a clinically relevant in vivo intraosseous tumor model overexpressing the platelet-derived growth factor D (PDGF D) to test the efficacy of a newly characterized VEGFR/PDGFR inhibitor, cediranib (also called AZD2171).
An intratibial-injection model was established utilizing DU145 cells without or with increased platelet-derived growth factor D (PDGF D) expression. Tumor-bearing mice were treated by daily gavage administration of cediranib and/or weekly i.p. injection of docetaxel for 7 weeks. Tibiae were monitored by in vivo/ex vivo x-rays and histomorphometry analysis was performed to estimate tumor volume and tumor-associated trabecular bone growth.
Cediranib reduced intraosseous growth of prostate tumors as well as tumor-associated bone responses. When compared to the standard chemotherapeutic agent docetaxel, cediranib exhibited a stronger inhibition of tumor-associated bone response. The efficacy of cediranib was further enhanced when the drug was co-administered with docetaxel. Importantly, the therapeutic benefits of cediranib and docetaxel are more prominent in intraosseous prostate tumors overexpressing PDGF D.
These novel findings support the utilization of cediranib, either alone or in combination with docetaxel, to treat bone metastatic prostate cancer exhibiting PDGF D expression.
PDGF D; Prostate Cancer; AZD2171; Metastasis; Markers
The increased use of bypass surgery in the treatment of ischemic cerebrovascular diseases requires a better understanding of the superficial temporal artery (STA) anatomy. This study is to describe the gross anatomy of STA in adult Korean population with respect to cranial surgery and to provide basic anatomic data for bypass surgery.
The study evaluated retrospectively 35 patients who visited the neurosurgery department at a single institution. For each patient, both the left and right STA (70 vessels) were evaluated by a 3-dimensional computed tomographic angiogramfor diameter and anatomic relationships to external landmarks.
Of 70 STAs, 69 had a bifurcation. Among these, 57 (82.6%) were above the superior margin of the zygomatic arch. The STA bifurcation was 53.2 ± 5.9 mm posterior to the keyhole, 9.5 ± 5.3 mm anterior to the posterior margin of condylar process of the mandible, and 21.7 ± 15.8 mm superior to the superior margin of the zygomatic arch. The inner diameter of the STA was 1.8 ± 0.5 mm at the superior margin of the zygomatic arch, and 1.4 ± 0.4 mm and 1.4 ± 0.5 mm for frontal and parietal branches, respectively. The 75.7% of frontal and 66.7% of parietal branches were suitable for microvascular anastomosis.
This present study demonstrated the STA in Korean adults, which may benefit the clinician in dealing with the surgical procedures related to this STA.
Carotid artery; External; Temporal arteries
Intraosseous arteriovenous malformation (AVM) in the craniofacial region is rare. When it occurs, it is predominantly located in the mandible and maxilla. We encountered a 43-year-old woman with Klippel-Trenaunay syndrome affecting the right lower extremity who presented with a left orbital chemosis and proptosis mimicking the cavernous sinus dural arteriovenous fistula. Computed tomography angiography revealed an intraosseous AVM of the sphenoid bone. The patient's symptoms were completely relieved after embolization with Onyx. We report an extremely rare case of intraosseous AVM involving the sphenoid bone, associated with Klippel-Trenaunay syndrome.
Arteriovenous malformations; Hemangioma; Primary intraosseous vascular malformation; Klippel-Trenaunay-Weber syndrome
Intra-cranial aneurysm can be incidental findings in patients with pituitary adenomas, and are usually located outside the pituitary region. However, the coexistence of intrasellar (not intracranial) aneurysms with pituitary adenomas is extremely rare. We report a patient with an incidental superior hypophygeal aneurysm embedded within a non-functional pituitary adenoma which was treated by transsphenoidal surgery after endovascular coil embolization.
Pituitary adenoma; Aneurysm; Therapeutic embolization; Surgical procedure
Alcohol dependence is characterized by persistent alcohol-seeking despite negative consequences. Previous studies suggest that maladaptive persistent behaviors reflect alcohol-induced brain changes that cause alterations in the cortico-striatal-limbic circuit.
Twenty one alcohol dependent patients and 24 age-matched healthy controls performed a decision-making task during functional MRI. We defined the medial orbitofrontal cortex (mOFC) as a region-of-interest and performed seed-based functional connectivity analysis.
Healthy controls were more flexible in adapting an alternative behavioral strategy, which correlated with stronger mOFC-dorsal striatum functional connectivity. In contrast, alcohol dependent patients persisted to the first established behavioral strategy. The mOFC-dorsal striatum functional connectivity was impaired in the alcohol-dependent patients, but increased in correlation with the duration of abstinence.
Our findings support that the disruption of the mOFC-striatal circuitry contribute to the maldaptive persistent behaviors in alcohol dependent patients.
Alcohol; Medial orbitofrontal cortex; Dorsal striatum; Decision-making; fMRI
Metastatic ovarian cancer is not an uncommon finding. Such tumors almost always originate from female genital tract, colon, stomach, or breast. Lung cancer is not a common origin of ovarian metastases. Of all metastatic ovarian tumors, approximately 0.3% arise from lung cancer. Ovarian torsion is not an uncommon finding, but ovarian torsion with cancer is rare. Here, we report a 44-year-old woman who was previously diagnosed with advanced stage lung cancer and who emergently visited our hospital for abdominal pain. An imaging work-up revealed, ovarian torsion and exploratory laparotomy was performed. Pathological examination led to the diagnosis ovarian metastasis from lung cancer. This is the first case of ovarian metastasis from lung cancer, ovarian torsion.
Lung cancer; Metastatic ovarian cancer; Ovarian torsion
Ssanghwa-tang (SHT) is a widely used medication for the treatment of fatigue, pain, inflammation, hypothermia, erectile dysfunction, cancer, and osteoporosis in Asia, however, role of SHT on the melanin synthesis has not been checked previously. Thus, the present study was designed to determine the effect of SHT on α-melanocyte stimulating hormone (α-MSH)-induced melanogensis and its mechanisms of action in murine B16F10 melanoma cells.
Cellular melanin content and tyrosinase activity in murine B16F10 melanoma cells were determined after α-MSH stimulation with or without pre-treatment of SHT at the concentration of 250 and 500 μg/ml. Expression level of tyrosinase, tyrosinase-related protein 1 (TRP-1), TRP-2, microphthalmia-associated transcription factor (MITF), and activation of c-AMP-dependent protein kinase (PKA), c-AMP-related element binding protein (CREB), and mitogen-activated protein kinases (MAPKs) were examined by Western blot analysis.
SHT significantly inhibited α-MSH-induced melanin synthesis and tyrosinase activity, and also decreased α-MSH-induced expression of MITF, tyrosinase, and TRP-1. In addition, SHT remarkably suppressed tyrosinase, CRE, and MITF luciferase reporter activity in a resting state as well as in α-MSH-stimulating condition. Phosphorylation of p38 MAPK by α-MSH stimulation was efficiently blocked by SHT pre-treatment. Moreover, SHT as an herbal cocktail showed synergistic anti-melanogenic effect compared with that of each single constituent herb.
SHT efficiently inhibited c-AMP-induced melanin synthesis in B16F10 cells via suppression of PKA and p38 MAPK signaling pathways and subsequently decreased the level of CREB phosphorylation, MITF, and melanogenic enzymes. These results indicate that SHT may be useful as herbal medicine for treating hyperpigmentation and cosmetics as a skin-whitening agent.
Ssanghwa-tang; Melanogenesis; p38 MAPK; PKA; MITF; Tyrosinase; B16F10 cells
Two variants of the inosine triphosphatase (ITPA: rs1127354, rs7270101) gene cause ITPA deficiency and protect against the hemolytic toxicity of ribavirin. We investigated the clinical significance of ITPA variants in Korean patients treated with pegylated interferon (PEG-IFN) plus ribavirin. Of the 133 patients, 108 were CC and 25 were non-CC at rs1127354 (groups A and B, respectively). On the other hand, at rs7270101 all 133 were AA. The mean values of Hemoglobin (Hgb) after 4, 8, and 12 weeks of treatment in groups A and B were 12.2 and 14.0, 11.8 and 13.2, and 11.5 and 12.9, respectively (P=0.001, 0.036, 0.036). Sustained virologic response (SVR) was achieved in 67.8% (40/59) of genotype 1 patients and in 75% (27/36) of non-genotype 1 patients. Regarding ITPA variants, SVR was achieved by 66% and 80% of genotype 1 (P=0.282), and by 78% and 71% (P=0.726) of non-genotype 1. SVR was not significantly different in groups A and B. In conclusion, non-CC at rs1127354 without involvement of rs7270101 is strongly associated with protection from ribavirin-induced anemia, however, ITPA genotype is not associated with SVR.
Hepatitis C, Chronic; Ribavirin; Anemia; ITPA; IL28B
The aim of this study was to investigate the genetic association of the FAT gene with schizophrenia in the Korean population, as well as analyzing the association of FAT gene with clinical variables.
Four variants within the FAT gene were investigated in 189 patients with schizophrenia and 119 healthy controls (rs2306987 A/C, rs2306990 T/C, rs2637777 G/T, and rs2304865 G/C).
Significant association at the rs273777 with schizophrenia was observed; however, rs2306987, rs2306990, and rs2304865 were not associated with schizophrenia. Haplotype analyses revealed that the haplotype A/T/T/G was associated with a significantly protective effect. Sliding window analysis (rs2637777 G/T and rs2304865 G/C) revealed the more common T/G haplotype, included in the A/T/T/G protective combination, showed a small protective effect, in particular the effect was due to the rs273777 T variant (minor allele).
The present finding suggests that FAT polymorphism may play a putative role in the susceptibility to schizophrenia in the Korean population. Further studies using a larger number of subjects should be performed to determine whether the FAT gene polymorphism may be truly involved in the development of schizophrenia.
Association; Cadherins; Polymorphism; Schizophrenia; Korean
The etiology and pathophysiology of takotsubo cardiomyopathy have not yet been fully clarified. We report a case of takotsubo cardiomyopathy associated with severe hypocalcemia secondary to hypoparathyroidism. A 69-year-old woman presented with acute pulmonary edema caused by severe left ventricular dysfunction with apical ballooning compatible with takotsubo cardiomyopathy. Laboratory tests revealed severe hypocalcemia secondary to idiopathic hypoparathyroidism. Coronary angiography showed normal coronary artery function. Her symptoms and signs of heart failure improved dramatically with the correction of hypocalcemia through calcium and calcitriol replacement.
Takotsubo cardiomyopathy; Hypocalcemia; Hypoparathyroidism
To investigate the effect of CoenzymeQ10 (CoQ10) on pain severity and cartilage degeneration in an experimental model of rat osteoarthritis (OA).
Materials and Methods
OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA) to the knee. Oral administration of CoQ10 was initiated on day 4 after MIA injection. Pain severity was assessed by measuring secondary tactile allodynia using the von Frey assessment test. The degree of cartilage degradation was determined by measuring cartilage thickness and the amount of proteoglycan. The mankin scoring system was also used. Expressions of matrix metalloproteinase-13 (MMP-13), interleukin-1β (IL-1β), IL-6, IL-15, inducible nitric oxide synthase (iNOS), nitrotyrosine and receptor for advanced glycation end products (RAGE) were analyzed using immunohistochemistry.
Treatment with CoQ10 demonstrated an antinociceptive effect in the OA animal model. The reduction in secondary tactile allodynia was shown by an increased pain withdrawal latency and pain withdrawal threshold. CoQ10 also attenuated cartilage degeneration in the osteoarthritic joints. MMP-13, IL-1β, IL-6, IL-15, iNOS, nitrotyrosine and RAGE expressions were upregulated in OA joints and significantly reduced with CoQ10 treatment.
CoQ10 exerts a therapeutic effect on OA via pain suppression and cartilage degeneration by inhibiting inflammatory mediators, which play a vital role in OA pathogenesis.
Filaggrin (FLG) is a key protein that facilitates the terminal differentiation of the epidermis and the formation of the skin barrier. Recent studies showed that atopic dermatitis (AD) associates closely with loss-of-function mutations in the FLG gene. Asian and European populations differ in the frequencies of FLG mutations. Several FLG mutations, including 3321delA, E2422X, K4671X, S2554X, and R501X, occur frequently in Chinese and Japanese populations. The association between three FLG null mutations and AD in Korean children was investigated.
The FLG mutations in 1,430 children (aged 0-18 years) with AD and 862 control subjects were genotyped by using the TaqMan assay.
The FLG null mutation E2422X was not detected in any patients with AD or control subjects. The R501X null mutation was detected in only one child with AD (0.1%). Children with AD had the 3321delA deletion significantly more frequently (2.4%) than the control subjects (0.0%, P<0.001). Children with AD also had a significantly higher combined allele frequency of the three FLG null mutations (2.6%) than the controls (0.0%, P<0.001). The 3321delA null mutation did not associate significantly with AD severity (P=0.842). When the patients with AD were divided into allergic AD and non-allergic AD patient groups, these two groups did not differ in terms of the frequency of 3321delA.
The Korean children had a lower frequency of FLG mutations than European populations. FLG null mutations may be associated with the development of AD in Korean children.
Filaggrin; atopic dermatitis; mutation; skin barrier
Recurrence after hepatic resection is one of the most important factors impacting the prognosis and survival of patients with hepatocellular carcinoma (HCC). We identified prognostic factors affecting overall survival (OS) and disease-free survival (DFS) in patients with HCC after hepatic resection.
This study was of a retrospective cohort design, and 126 patients who underwent hepatic resection for HCC at Gachon University Gil Medical Center between January 2005 and December 2010 were enrolled. Various clinical, laboratory, and pathological data were evaluated to determine the prognostic factors affecting OS and DFS.
Two- and 4-year OS and 2- and 4-year DFS were 78.1% and 65% and 51.1% and 26.6%, respectively. In a multivariate analysis, preoperative α-fetoprotein (> 400 ng/mL), tumor size (≥ 5 cm), multiple tumors (two or more nodules), presence of portal vein invasion, modified Union for International Cancer Control (UICC) stage III/IV, and Barcelona Clinic Liver Cancer (BCLC) stage B/C were independent prognostic factors affecting a shorter OS. In the multivariate analysis, presence of microvascular invasion, modified UICC stage III/IV, and BCLC stage B/C were independent prognostic factors for a shorter DFS.
The presence of vascular invasion was an independent poor prognostic factor for OS and DFS in patients with HCC after hepatic resection. Thus, close postoperative surveillance for early detection of recurrence and additional treatments are urgently needed in patients with vascular invasion after hepatic resection.
Carcinoma, hepatocellular; Hepatic resection; Prognosis; Vascular invasion
To suggest a new useful diagnostic technique, principles of the selective excitation technique-magnetic resonance images (Proset-MRI), and to know the precise radiologic findings that can prove symptomatic foraminal and extraforaminal stenosis at L5-S1.
Nineteen patients with symptomatic L5-S1 stenosis were checked by Proset-MRI. Four patients were performed decompressive surgery and 15 patients were performed selective nerve root block (SNRB) at L5. The pain scale of patients was checked by Visual Analogue Scale (VAS) scores at the pre- and post-treatment state.
Proset-MRI findings of patients with symptomatic stenosis are root swelling (RS) and indentation. The comparisons with VAS scores had a meaningful statistical result at each RS (p<0.01) and indentation (p<0.01). However, the findings of RS combined with indentation lacked statistical significance (p=0.0249). In addition, according to a comparison with the treatment modalities, reducing of VAS scores had statistical meaningful significance in decompressive surgery cases (p<0.01), and also in SNRB cases (p<0.01) after a 3-month follow-up period.
The three dimensional Proset-MRI is very useful and sensitive technique to diagnose the symptomatic foraminal and extraforaminal stenosis at L5-S1.
Proset-MRI; Foraminal and extraforaminal stenosis; Nerve root swelling; Indentation