We report a rare case of rhabdomyosarcoma spontaneously arising in an anterior mediastinal teratoma in a 47-year-old male. The patient was found to have an anterior mediastinal mass on a chest X-ray, which was taken two months before his presentation to Asan Medical Center. A subsequent computed tomography scan revealed an 8.9×7.1×8.0 cm heterogeneous mass in the anterior mediastinum. He underwent an excision via median sternotomy. The histopathologic study identified a mature teratoma with embryonal rhabdomyosarcoma.
Mediastinal neoplasms; Rhabdomyosarcoma; Teratoma; Teratoma with malignant transformation
Elevated levels of serum carcinoembryonic antigen (CEA) following a curative resection of colorectal cancer (CRC) indicate recurrence; however, the levels of CEA may be elevated above the normal limit without recurrence. The aim of this study is to analyze the diagnostic accuracy of elevated serum CEA for predicting recurrence in postoperative stage II and stage III CRC patients.
A total of 336 stage II and stage III CRC patients who underwent a curative resection between January 2005 and October 2009 were enrolled. Sensitivities, specificities, positive predictive values (PPVs), negative predictive values (NPVs), likelihood ratios and post-test probabilities of recurrence associated with elevated CEA were analyzed and compared.
The median follow-up duration was 45 months (36 to 134 months). Twenty-seven of 189 stage II patients (14.3%) and 52 of 147 stage III patients (35.4%) developed recurrence during the follow-up period. Sensitivities, specificities, PPVs, and NPVs of elevated CEA were 37.0%, 91.4%, 41.7%, and 89.7%, respectively, in stage II patients and 46.2%, 90.5%, 72.7%, and 75.4% in stage III patients. Post-test probabilities of recurrence associated with elevated CEA were 41.8% in stage II patients and 71.9% in stage III patients.
The predictive performance of the probability of recurrence associated with elevated serum CEA after a curative resection in stage II CRC patients is lower than that in stage III CRC patients.
Carcinoembryonic antigen; Tumor marker; Colorectal neoplasms; Recurrence; Accuracy
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.
In this study we examined the in vivo and in vitro effects and mechanisms of action of curcumin on the development of acute graft-versus-host disease (GVHD) using a murine model.
Mixed lymphocyte reactions were used to determine the in vitro effects of curcumin. Treatment with curcumin attenuated alloreactive T cell proliferation and inhibited the production of interferon (IFN)-γ and interleukin (IL)-17. In a murine acute GVHD model, transplantation of curcumin-treated allogeneic splenocytes into irradiated recipient mice significantly reduced the clinical severity scores of acute GVHD manifested in the liver, skin, colon and lung as compared with animals receiving vehicle-treated splenocytes. c-Fos and c-Jun expression levels in the skin and intestine, which are major target organs, were analyzed using immunohistochemical staining. Expression of both proteins was reduced in epithelial tissues of skin and intestine from curcumin-treated GVHD animals. The IFN-γ-expressing CD4+ splenocytes and IFN-γ-expressing lymph node cells were dramatically decreased in curcumin-treated mice. In contrast, CD4+Foxp3+ splenocytes were increased in the curcumin-treated acute GVHD animals. Flow cytometric analysis revealed that animals transplanted with curcumin-treated allogeneic splenocytes showed increased populations of CD4+ regulatory T cells (Tregs) as well as CD8+ Treg cells, compared to animals administered vehicle-treated splenocytes. Curcumin-treated acute GVHD animals could have a change in B cell subpopulations.
In the present study, we investigated the efficacy and mechanism of action of curcumin treatment against acute GVHD. The acute GVHD mice administered with curcumin-treated splenocytes showed significantly reduced severity of acute GVHD. Curcumin exerted in vivo preventive effects on acute GVHD by reciprocal regulation of T helper 1 (Th1) and Treg (both CD4+ and CD8+ Treg) cell lineages as well as B cell homeostasis.
Lung cancer in never-smokers ranks as the seventh most common cause of cancer death worldwide, and the incidence of lung cancer in non-smoking Korean women appears to be steadily increasing. To identify the effect of genetic polymorphisms on lung cancer risk in non-smoking Korean women, we conducted a genome-wide association study of Korean female non-smokers with lung cancer. We analyzed 440,794 genotype data of 285 cases and 1,455 controls, and nineteen SNPs were associated with lung cancer development (P < 0.001). For external validation, nineteen SNPs were replicated in another sample set composed of 293 cases and 495 controls, and only rs10187911 on 2p16.3 was significantly associated with lung cancer development (dominant model, OR of TG or GG, 1.58, P = 0.025). We confirmed this SNP again in another replication set composed of 546 cases and 744 controls (recessive model, OR of GG, 1.32, P = 0.027). OR and P value in combined set were 1.37 and < 0.001 in additive model, 1.51 and < 0.001 in dominant model, and 1.54 and < 0.001 in recessive model. The effect of this SNP was found to be consistent only in adenocarcinoma patients (1.36 and < 0.001 in additive model, 1.49 and < 0.001 in dominant model, and 1.54 and < 0.001 in recessive model). Furthermore, after imputation with HapMap data, we found regional significance near rs10187911, and five SNPs showed P value less than that of rs10187911 (rs12478012, rs4377361, rs13005521, rs12475464, and rs7564130). Therefore, we concluded that a region on chromosome 2 is significantly associated with lung cancer risk in Korean non-smoking women.
Lung Neoplasms; Genome-Wide Association Study; Non-Smoking Women
Mucormycosis is a rare fungal disease that holds a fatal opportunistic fungal infection in diabetes mellitus, hematological malignancy, and immunocompromised host. Isolated pulmonary mucormycosis is extremely rare. Optimal therapy is a combined medical-surgical approach and a management of the patient's underlying disease. Herein, we report a case-study of isolated pulmonary mucormycosis which was being presented as multiple lung nodules in a patient with no underlying risk factors. Considering that the patient had poor pulmonary functions, we treated him with only antifungal agent rather than a combined medical-surgical approach. After treatment with antifungal agent for six months, the nodules of pulmonary mucormycosis were improved with the prominent reductions of size on the computed tomography.
Mucormycosis; Lung; Immunocompetence; Posaconazole
Accumulating evidence suggests that HtrA1 (high-temperature requirement A1) is involved in modulating crucial cellular processes and implicated in life-threatening diseases, such as cancer and neuropathological disorders; however, the exact functions of this protease in vivo remain unknown. Here, we show that loss of HtrA1 function increases fibroblast growth factor 8 (FGF8) mRNA levels and triggers activation of FGF signaling, resulting in dorsalization in zebrafish embryos. Notably, HtrA1 directly cleaves FGF8 in the extracellular region, and this cleavage results in decreased activation of FGF signaling, which is essential for many physiological processes. Therefore, HtrA1 is indispensable for dorsoventral patterning in early zebrafish embryogenesis and serves as a key upstream regulator of FGF signaling through the control of FGF levels. Furthermore, this study offers insight into new strategies to control human diseases associated with HtrA1 and FGF signaling.
Hypocalcemia is the most common complication after total thyroidectomy. The purpose of this study was to determine whether measurement of intact parathyroid hormone (i-PTH) level in thyroidectomy patients could predict hypocalcemia.
Materials and Methods
We performed a prospective study of patients undergoing total thyroidectomy. Serum concentration of i-PTH, total calcium (Ca), ionized calcium (Ca2+), phosphate (P), magnesium (Mg), and albumin were measured preoperatively and at 0 hour, 6 hours, 12 hours, 24 hours, 48 hours, and 72 hours postoperatively.
108 patients were recruited to the study. A total of 50 patients (46%) experienced hypocalcemia. The serum i-PTH concentration was linearly related to the time of measurement, while concentrations of P, Mg, albumin, Ca, and Ca2+ were not. We compared odds ratios, and found that the concentration of i-PTH at 6 hours post operation was the most closely related to the occurrence of hypocalcemic symptom. On ROC analysis using i-PTH level at 6 hours, an i-PTH level of 10.6 mg/dL was found to maximize both sensitivity and specificity at the same time point.
We found that i-PTH was a predictor of hypocalcemia, and that the earliest predictor of hypocalcemic symptoms was an i-PTH concentration lower than 10.6 mg/dL obtained 6 hours after total thyroidectomy.
Thyroidectomy; hypocalcemia; parathyroid hormone; surgery
C57BL/6 mice are known to be resistant to the development of collagen-induced arthritis (CIA). However, they show a severe arthritic phenotype when the Ifng gene is deleted. Although it has been proposed that IFN-γ suppresses inflammation in CIA via suppressing Th17 which is involved in the pathogenesis of CIA, the exact molecular mechanism of the Th17 regulation by IFN-γ is poorly understood. This study was conducted to 1) clarify that arthritogenic condition of IFN-γ knockout (KO) mice is dependent on the disinhibition of Th17 and 2) demonstrate that IFN-γ-induced indoleamine2,3dioxgenase (IDO) is engaged in the regulation of Th17. The results showed that the IFN-γ KO mice displayed increased levels of IL-17 producing T cells and the exacerbation of arthritis. Also, production of IL-17 by the splenocytes of the IFN-γ KO mice was increased when cultured with type II collagen. When Il17 was deleted from the IFN-γ KO mice, only mild arthritis developed without any progression of the arthritis score. The proportion of CD44highCD62Llow memory-like T cells were elevated in the spleen, draining lymph node and mesenteric lymph node of IFN-γ KO CIA mice. Meanwhile, CD44lowCD62Lhigh naïve T cells were increased in IFN-γ and IL-17 double KO CIA mice. When Th17 polarized CD4+ T cells of IFN-γ KO mice were co-cultured with their own antigen presenting cells (APCs), a greater increase in IL-17 production was observed than in co-culture of the cells from wild type mice. In contrast, when APCs from IFN-γ KO mice were pretreated with IFN-γ, there was a significant reduction in IL-17 in the co-culture system. Of note, pretreatment of 1-methyl-DL- tryptophan, a specific inhibitor of IDO, abolished the inhibitory effects of IFN-γ. Given that IFN-γ is a potent inducer of IDO in APCs, these results suggest that IDO is involved in the regulation of IL-17 by IFN-γ.
Aim of the study
Excessive inflammation can lead to tissue damage and dysfunction of vital organs. Hence, regulating inflammatory response is a viable therapeutic approach. In Asian countries, various inflammatory diseases have often effectively been treated with herbal remedies including the root extract of Aralia continentalis Kitagawa (Araliaceae). Here, we investigated the effect of kaurenoic acid (ent-kaur-16-en-19-oic acid: KA), a diterpenoid that is extracted from Aralia continentalis Kitagawa root, on inflammation.
Western blot and RT-PCR analyses show that KA induced the nuclear localization of Nrf2 as low as 1 nM in concentration and that KA treatment induced the expression of Nrf2 dependent genes such as GCLC and HO-1. On the other hand, KA did not affect the degradation of cytoplasmic IκB-α, the nuclear localization of RelA (p65), and NF-κB transcriptional activity in RAW 264.7 cells treated with endotoxin. Consistent with these data, KA treatment failed to suppress gene expression of representative pro-inflammatory mediators including COX-2, nitric oxide, IL-1β, TNF-α, and IL-12, indicating that KA did not have an important impact on NF-κB activation.
Together, these results show that KA was an effective activator of Nrf2, and suggest that the beneficial effects of A. continentalis Kitagawa root extract are, at least in part, mediated by activating Nrf2.
Inflammation; Kaurenoic acid; Herbal treatment; anti-inflammation; Nrf2
Objectives. Strong aversions to acupuncture have been an obstacle to understanding its intrinsic action of acupuncture. Thus, it is necessary to evaluate the nature and extent of fear of acupuncture treatment. Our study aims to develop and validate an instrument that evaluates a patient's fear of acupuncture treatment. Methods. We have developed an acupuncture fear scale, a 16-item instrument which assesses the acupuncture fear score and uses it to survey 275 participants in South Korea, thus testing the reliability and validity of the instrument. Results. Internal consistency was high (Cronbach's alpha = 0.935). Test-retest reliability (Spearman's rank correlation coefficient) among 33 participants out of 275 ranged from 0.565 to 0.797 (P < 0.001). Principal component analysis revealed two factors accounting for 68% of the variance, which are painful sensation and possible adverse events, respectively. The acupuncture fear scale was positively correlated with the total of fear of pain questionnaire-III (r = 0.423, P < 0.001). Conclusions. The acupuncture fear scale can be a valid and reliable instrument that can measure fear of acupuncture treatment. These results strongly suggest that it would be a clinically useful tool to assess fear of acupuncture in the acupuncture clinic setting and an important instrument to understand the complex social-behavioral component of acupuncture modality.
To investigate the clinical effect of extracorporeal shock wave therapy (ESWT) in patients with secondary lymphedema after breast cancer treatment.
In a prospective clinical trial, ESWT was performed consecutively 4 times over two weeks in 7 patients who were diagnosed with stage 3 secondary lymphedema after breast cancer treatment. Each patient was treated with four sessions of ESWT (0.056-0.068 mJ/mm2, 2,000 impulses). The parameters were the circumference of the arm, thickness of the skin and volume of the arm. We measured these parameters with baseline values before ESWT and repeated the evaluation after each ESWT treatment. Subjective data on skin thickness, edema and sensory impairment were obtained using a visual analogue scale (VAS).
The mean volume of the affected arm after four consecutive ESWT was significantly reduced from 2,332 to 2,144 mL (p<0.05). The circumference and thickness of the skin fold of the affected arm were significantly decreased after the fourth ESWT (p<0.05). The three VAS scores were significantly improved after the fourth ESWT. Almost all patients were satisfied with this treatment and felt softer texture in their affected arm after treatment.
ESWT is an effective modality in the treatment of stage 3 lymphedema after breast cancer treatment. ESWT reduced the circumference and the thickness of arms with lymphedema and satisfied almost all patients with lymphedema. Therefore, this treatment provides clinically favorable outcome to patients with breast cancer-related lymphedema.
Lymphedema; Breast neoplasms; High-energy shock waves; Physiotherapy
The orbitofrontal cortex (OFC) has consistently been implicated in the pathology of both drug and behavioral addictions. However, no study to date has examined OFC thickness in internet addiction. In the current study, we investigated the existence of differences in cortical thickness of the OFC in adolescents with internet addiction. On the basis of recently proposed theoretical models of addiction, we predicted a reduction of thickness in the OFC of internet addicted individuals.
Participants were 15 male adolescents diagnosed as having internet addiction and 15 male healthy comparison subjects. Brain magnetic resonance images were acquired on a 3T MRI and group differences in cortical thickness were analyzed using FreeSurfer. Our results confirmed that male adolescents with internet addiction have significantly decreased cortical thickness in the right lateral OFC (p<0.05).
This finding supports the view that the OFC alterations in adolescents with internet addiction reflect a shared neurobiological marker of addiction-related disorders in general.
Internet addiction; Magnetic resonance imaging; Cortical thickness; Orbitofrontal cortex
Cerebrospinal fluid (CSF) plays an important role in providing brain tissue with a stable internal environment as well as in absorbing mechanical and thermal stresses. From its initial composition, derived from the amniotic fluid trapped by the closure of neuropores, CSF is modified by developing and differentiating ependymal cells lining the ventricular surface or forming the choroid plexus. Its osmolarity and ionic composition brings about a change through the action of many channels expressed on the ependymal cells. Some newly discovered transient receptor potential (TRP) channels are known to be expressed in the choroid plexus ependyma. To detect additional TRP channel expression, immunohistochemical screening was performed at the choroid plexus of 13-, 15-, 17-, and 19-day embryos, using antibodies against TRPV1, TRPV3, and TRPA1, and the expression was compared with those in the adult TRP channels. The level of TRP channel expression was higher in the choroid plexus which suggests more active functioning of TRP channels in the developing choroid plexus than the ventricular lining ependyma in the 15- and 17-day embryos. All the expression of TRP channels decreased at the 19th day of gestation. TRPA1 was expressed at a higher level than TRPV1 and TRPV3 in almost all stages in both the choroid plexus and ventricular lining epithelium. The highest level of TRPV1 and TRPV3 expression was observed in association with the glycogen deposits in the cytoplasm of the choroid plexus ependymal cells of the 15- and 17-day embryos.
Ependyma; Choroid plexus; Transient receptor potential channels; Embryonic development
Internet addiction has become increasingly recognized as a mental disorder, though its neurobiological basis is unknown. This study used functional neuroimaging to investigate whole-brain functional connectivity in adolescents diagnosed with internet addiction. Based on neurobiological changes seen in other addiction related disorders, it was predicted that connectivity disruptions in adolescents with internet addiction would be most prominent in cortico-striatal circuitry.
Participants were 12 adolescents diagnosed with internet addiction and 11 healthy comparison subjects. Resting-state functional magnetic resonance images were acquired, and group differences in brain functional connectivity were analyzed using the network-based statistic. We also analyzed network topology, testing for between-group differences in key graph-based network measures.
Adolescents with internet addiction showed reduced functional connectivity spanning a distributed network. The majority of impaired connections involved cortico-subcortical circuits (∼24% with prefrontal and ∼27% with parietal cortex). Bilateral putamen was the most extensively involved subcortical brain region. No between-group difference was observed in network topological measures, including the clustering coefficient, characteristic path length, or the small-worldness ratio.
Internet addiction is associated with a widespread and significant decrease of functional connectivity in cortico-striatal circuits, in the absence of global changes in brain functional network topology.
Fibroblast-like synoviocytes (FLSs) are a major cell population of the pannus that invades adjacent cartilage and bone in rheumatoid arthritis (RA). The study was undertaken to determine the effect of interleukin-17 (IL-17) on the survival and/or proliferation of FLSs from RA patients and to investigate whether signal tranducer and activator of transcription 3 (STAT3) is implicated in this process.
Bcl-2 and Bax expression in FLSs was determined using the real-time PCR and western blot analysis. The expression of Bcl-2 and phosphoSTAT3 in synovial tissues was investigated by confocal microscope. Apoptosis of FLSs was detected by Annexin V/propidium iodide staining and/or phase contrast microscopy. The proliferation of FLSs was determined by CCK-8 ELISA assay.
The pro-apoptotic Bax is decreased and anti-apoptotic Bcl-2 is increased in FLSs from RA patients compared with those from patients with osteoarthritis (OA). IL-17 upregulated the expression of Bcl-2 in FLSs from RA patients, but not in FLSs from OA patients. STAT3 was found to mediate IL-17-induced Bcl-2 upregulation in FLSs from RA patients. Additionally, IL-17 promoted the survival and proliferation of FLSs from RA patients. Most importantly, treatment with STAT3 inhibitor reversed the protective effect of IL-17 on FLSs apoptosis induced by sodium nitroprusside (SNP).
Our data demonstrate that STAT3 is critical in IL-17-induced survival of FLS from RA patients. Therefore, therapeutic strategies that target the IL-17/STAT3 pathway might be strong candidates for RA treatment modalities.
Bone destruction and inflammation are closely linked. Cytokines play an important role in inflammatory bone destruction by upregulating the receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL). The direct role of cytokines that act in a non-RANKL-dependent manner has yet to be elucidated. The aim of this study was to investigate the direct osteoclastogenic properties of inflammatory cytokines at different time-points of osteoclastogenesis. Mouse bone marrow macrophages were stimulated with the macrophage colony-stimulating factor (M-CSF) and various concentrations of RANKL. Inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-17 and IL-23, were added to the culture system of osteoclastogenesis. Two time-points of cytokine treatment were set. The ‘early’ effect of each cytokine was investigated at the time of first RANKL treatment, whereas the ‘late’ effect was investigated 48 h after the first RANKL challenge. Osteoclast differentiation and function were assessed using an osteoclast marker [tartrate-resistant acid phosphatase (TRAP)] and by visualization of pit formation. A permissive level of RANKL was required for cytokine-associated osteoclastogenesis in all experiments. In the M-CSF/RANKL monocellular culture system, IL-1β enhanced and IL-6 decreased osteoclast formation in a dose-dependent manner, regardless of temporal differences. Other cytokines showed various responses according to the phase of osteoclast maturation and the concentration of each cytokine and RANKL. Furthermore, luciferase assays showed that both IL-1β and RANKL activated the NF-κB signaling pathway. Collectively, our data revealed that targeting IL-1β may be a promising strategy to inhibit inflammation-associated bone destruction and osteoporosis.
inflammation; osteoclast; receptor activator nuclear factor-κB ligand; interleukin-1β; interleukin-6; nuclear factor-κB
We aimed to quantify periarticular osteoporosis and investigate its significance in 45 patients with rheumatoid arthritis (RA) and 106 controls. Dual-energy X-ray absorptiometry (DXA) was used to determine the ratio of shaft to periarticular bone mineral density (BMD) as an index of periarticular demineralization. Periarticular osteoporosis was measured by conventional radiography. The BMDs of shaft and periarticular regions in eight designated areas on proximal phalanges were quantified. Clinical variables were examined to identify risk factors for periarticular osteoporosis. The assessment of periarticular osteoporosis on X-ray images reached a moderate degree of interobserver agreement among four physicians (ĸ = 0.47). For BMD quantification, we designed three types of mathematical formulae: the ratio of shaft to periarticular BMD, the mean of the ratios, and the ratio of the sums. These ratios were significantly higher in the patients with early RA (disease duration ≤ 3 yr) than in controls (P < 0.01). The findings were not as distinctive in patients with established RA. Body mass index, cumulative dose of corticosteroid, and C-terminal telopeptide were correlated with BMD ratios. Conclusively, DXA-assisted localized quantification and BMD ratio calculations are feasible for assessing periarticular demineralization. Periarticular osteoporosis is a relatively distinctive feature of early RA.
Bone Density; Arthrits; Rheumatoid; Periarticular Osteopenia
Although renal calcium crystal deposits (nephrocalcinosis) may occur in acute phosphate poisoning as well as type 1 renal tubular acidosis (RTA), hyperphosphatemic hypocalcemia is common in the former while normocalcemic hypokalemia is typical in the latter. Here, as a unique coexistence of these two seperated clinical entities, we report a 30-yr-old woman presenting with carpal spasm related to hypocalcemia (ionized calcium of 1.90 mM/L) due to acute phosphate poisoning after oral sodium phosphate bowel preparation, which resolved rapidly after calcium gluconate intravenously. Subsequently, type 1 RTA due to Sjögren's syndrome was unveiled by sustained hypokalemia (3.3 to 3.4 mEq/L), persistent alkaline urine pH (> 6.0) despite metabolic acidosis, and medullary nephrocalcinosis. Through this case report, the differential points of nephrocalcinosis and electrolyte imbalances between them are discussed, and focused more on diagnostic tests and managements of type 1 RTA.
Hypocalcemia; Nephrocalcinosis; Sodium Phosphate; Distal RTA; Sjögren's Syndrome
The antiobesity effects of a P. aviculare ethanol extract (PAE) in high-fat diet- (HFD-) induced obese mice were investigated. The mice were fed an HFD or an HFD supplemented with PAE (400 mg/kg/day) for 6.5 weeks. The increased body weights, adipose tissue weight, and adipocyte area as well as serum total triglyceride, leptin, and malondialdehyde concentrations were decreased in PAE-treated HFD-induced obese mice relative to the same measurements in untreated obese mice. Furthermore, PAE significantly suppressed the elevated mRNA expression levels of sterol regulatory element-binding protein-1c, peroxisome proliferator-activated receptor γ, fatty acid synthase, and adipocyte protein 2 in the white adipose tissue of obese mice. In addition, PAE treatment of 3T3-L1 cells inhibited adipocyte differentiation and fat accumulation in a dose-dependent manner. These results suggest that PAE exerts antiobesity effects in HFD-induced obese mice through the suppression of lipogenesis in adipose tissue and increased antioxidant activity.
Metabolic syndrome is associated with visceral obesity, insulin resistance and an increased risk of cardiovascular diseases. Visceral fat tissue primarily consists of adipocytes that secrete cytokines leading to a state of systemic inflammation in obese conditions. One of the IGF-independent functions of IGFBP-3 is its role as an anti-inflammatory molecule. Our study in obese adolescents show a decrease in total IGFBP-3 levels and increase in proteolyzed IGFBP-3 in circulation when compared to their normal counterparts and establishes a positive correlation between IGFBP-3 proteolysis and adiposity parameters as well as insulin resistance. In human adipocytes, we show that IGFBP-3 inhibits TNF-α-induced NF-κB activity in an IGF-independent manner, thereby restoring the deregulated insulin signaling and negating TNF-α-induced inhibition of glucose uptake. IGFBP-3 further inhibits TNF-α, CRP and high glucose-induced NF-κB activity in human aortic endothelial cells (HAECs) and subsequently suppresses monocyte adhesion to HAEC through the IGFBP-3 receptor. In conclusion, these findings suggest that reduced levels of IGFBP-3 in circulation and reduced expression of IGFBP-3 in macrophages in obesity may result in suppression of its anti-inflammatory functions and therefore IGFBP-3 may present itself as a therapeutic for obesity-induced insulin resistance and for events occurring in the early stages of atherosclerosis.
The timing of referral to a nephrologist may influence the outcome of chronic kidney disease patients, but its impact has not been evaluated thoroughly. The results of a recent study showing an association between early referral and patient survival are still being debated. A total of 1028 patients newly diagnosed as end-stage renal disease (ESRD) from July 2008 to October 2011 were enrolled. Early referral (ER) was defined as patients meeting with a nephrologist more than a year before dialysis and dialysis education were provided, and all others were considered late referral (LR). The relationship of referral pattern with mortality in ESRD patients was explored using a Cox proportional hazards regression models. Time from referral to dialysis was significantly longer in 599 ER patients than in 429 LR patients (62.3±58.9 versus 2.9±3.4 months, P<0.001). Emergency HD using a temporary vascular catheter was required in 485 (47.2%) out of all patients and in 262 (43.7%) of ER compared with 223 (52.0%) of LR (P = 0.009). After 2 years of follow-up, the survival rate in ER was better than that in LR (hazard ratio [HR] 2.38, 95% confidence interval [CI] 1.27–4.45, P = 0.007). In patients with diabetes nephropathy, patient survival was also significantly higher in ER than in LR (HR 4.74, 95% CI 1.73–13.00, P = 0.002). With increasing age, HR also increased. Timely referral to a nephrologist in the predialytic stage is associated with reduced mortality.
Air pollution’s mortality effects may differ by subpopulation; however, few studies have investigated this issue in Asia. We investigated susceptibility to air pollutants on total, cardiovascular, and respiratory mortality in Seoul, Korea for the period 2000 – 2007. We applied time-stratified case-crossover analysis, which allows direct modeling of interaction terms, to estimate susceptibility based on sex, age, education, marital status, and occupation. An interquartile range increase in pollution was associated with odds ratios of 0.94 (95% confidence interval, 0.25 – 1.62), 2.27 (1.03–3.53), 1.94 (0.80 – 3.09), and 2.21 (1.00 – 3.43) for total mortality and 1.95 (0.64 – 3.27), 4.82 (2.18 – 7.54), 3.64 (1.46 – 5.87), and 4.32 (1.77 – 6.92) for cardiovascular mortality for PM10, nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide (CO), respectively. Ozone effect estimates were positive, but not statistically significant. Results indicate that some populations are more susceptible than others. For total or cardiovascular mortality, associations were higher for males, those 65 – 74 years, and those with no education or manual occupation for some pollutants. For example, the odds ratio for SO2 and cardiovascular mortality was 1.19 (1.03 – 1.37) times higher for those with manual occupations than professional occupations. Our findings provide evidence that some populations are more susceptible to the effects of air pollution than others, which has implications for public policy and risk assessment for susceptible subpopulations.
air pollution; effect modifiers; mortality; time-stratified case–crossover analysis; susceptible subpopulations
Background and Purpose
Although plasmapheresis is becoming standard practice as a rescue therapy for neuromyelitis optica (NMO), evidence for the therapeutic efficacy of plasmapheresis is limited, and the effect of plasmapheresis on anti-aquaporin-4 (AQP4) levels in patients with NMO has not been reported. Here, our objective was to evaluate the clinical efficacy of therapeutic plasmapheresis and its effect on anti-AQP4 antibody levels in patients with NMO spectrum disorder (NMOSD).
We retrospectively reviewed the medical records of 15 patients with NMOSD who had 18 acute attacks and received plasmapheresis because they did not respond to high-dose intravenous methylprednisolone (IVMP) therapy. Anti-AQP4 antibodies were measured before and after plasmapheresis. The primary outcomes were functional improvements immediately and 6 months after plasmapheresis, and the secondary outcome was the change in anti-AQP4 antibody serum levels following plasmapheresis.
Plasmapheresis following IVMP therapy led to significant improvement in 50% of the 18 attacks in 15 patients immediately after the procedure was completed, and in 78% (14 attacks) after 6 months. Plasmapheresis was generally well tolerated in all patients. Anti-AQP4 antibody serum levels declined significantly following plasmapheresis, to a mean of 15% of the preplasmapheresis levels. Lower scores on the visual outcome scale recorded before an attack were associated with significant immediate improvement upon the completion of plasmapheresis (p=0.03).
Plasmapheresis following IVMP therapy effectively removed anti-AQP4 antibodies and was accompanied by a substantial improvement in the neurological disability of patients with NMOSD. Lower levels of pre-existing neurological damage may be associated with an improved acute response to plasmapheresis.
plasmapheresis; neuromyelitis optica; anti-aquaporin-4 antibody