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1.
Metabolism ; 105: 154173, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32035087

RESUMO

OBJECTIVE: Brown adipocytes play important roles in the regulation of energy homeostasis by uncoupling protein 1-mediated non-shivering thermogenesis. Recent studies suggest that brown adipocytes as novel therapeutic targets for combating obesity and associated diseases, such as type II diabetes. However, the molecular mechanisms underlying brown adipocyte differentiation and function are not fully understood. METHODS: We employed previous findings obtained through proteomic studies performed to assess proteins displaying altered levels during brown adipocyte differentiation. Here, we performed assays to determine the functional significance of their altered levels during brown adipogenesis and development. RESULTS: We identified isocitrate dehydrogenase 1 (IDH1) as upregulated during brown adipocyte differentiation, with subsequent investigations revealing that ectopic expression of IDH1 inhibited brown adipogenesis, whereas suppression of IDH1 levels promoted differentiation of brown adipocytes. Additionally, Idh1 overexpression resulted in increased levels of intracellular α-ketoglutarate (α-KG) and inhibited the expression of genes involved in brown adipogenesis. Exogenous treatment with α-KG reduced brown adipogenesis during the early phase of differentiation, and ChIP analysis revealed that IDH1-mediated α-KG reduced trimethylation of histone H3 lysine 4 in the promoters of genes associated with brown adipogenesis. Furthermore, administration of α-KG decreased adipogenic gene expression by modulating histone methylation in brown adipose tissues of mice. CONCLUSION: These results suggested that the IDH1-α-KG axis plays an important role in regulating brown adipocyte differentiation and might represent a therapeutic target for treating metabolic diseases.

2.
Clin Neurophysiol ; 131(1): 46-53, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31751839

RESUMO

OBJECTIVE: To investigate gait characteristics in patients with freezing of gait (FOG) after hypoxic-ischemic brain injury (HIBI) and to elucidate neural correlates for FOG using F-18 fluoro-2-deoxy-d-glucose positron emission tomography. METHODS: We enrolled 12 patients with FOG after HIBI and 17 patients without FOG after HIBI. We performed three-dimensional gait analyses and compared each parameter and gait variability. Brain metabolism was measured, and we compared regional brain metabolism using a voxel-by-voxel-based statistical mapping analysis. RESULTS: The FOG group revealed a significantly decreased joint range of motion (ROM), particularly in the sagittal plane for three-joint summated ROM (p < 0.0025). Spatiotemporal results demonstrated that stride length and step length were decreased in the with FOG group (p < 0.005). FOG severity was negatively correlated with brain metabolism in the left thalamus, and three-joint summated ROM in the sagittal plane was positively associated with brain metabolism in the left thalamus and midbrain (p < 0.05). CONCLUSIONS: Central organizational level amplitude disorder may play an important role in the pathophysiology, and disturbance in the cholinergic pathway might contribute to the development of FOG in patients with HIBI. SIGNIFICANCE: These findings contribute to understanding FOG in HIBI.

3.
Int J Mol Sci ; 20(24)2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31847135

RESUMO

Tumor necrosis factor-α (TNF-α)-driven inflammatory reaction plays a crucial role in the initiation of liver fibrosis. We herein attempted to design genetically engineered adipose-derived stem cells (ASCs) producing etanercept (a potent TNF-α inhibitor), and to determine the anti-fibrotic potential of the secretome released from the etanercept-synthesizing ASCs (etanercept-secretome). First, we generated the etanercept-synthesizing ASCs by transfecting the ASCs with mini-circle plasmids containing the gene insert encoding for etanercept. We subsequently collected the secretory material released from the etanercept-synthesizing ASCs and determined its anti-fibrotic effects both in vitro (in thioacetamide [TAA]-treated AML12 and LX2 cells) and in vivo (in TAA-treated mice) models of liver fibrosis. We observed that while etanercept-secretome increased the viability of the TAA-treated AML12 hepatocytes (p = 0.021), it significantly decreased the viability of the TAA-treated LX2 HSCs (p = 0.021). In the liver of mice with liver fibrosis, intravenous administration of the etanercept-secretome induced significant reduction in the expression of both fibrosis-related and inflammation-related markers compared to the control group (all Ps < 0.05). The etanercept-secretome group also showed significantly lower serum levels of liver enzymes as well as pro-inflammatory cytokines, such as TNF-α (p = 0.020) and IL-6 (p = 0.021). Histological examination of the liver showed the highest reduction in the degree of fibrosis in the entanercept-secretome group (p = 0.006). Our results suggest that the administration of etanercept-secretome improves liver fibrosis by inhibiting TNF-α-driven inflammation in the mice with liver fibrosis. Thus, blocking TNF-α-driven inflammation at the appropriate stage of liver fibrosis could be an efficient strategy to prevent fibrosis.

4.
Pain Physician ; 22(6): E563-E572, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31775409

RESUMO

BACKGROUND: We have applied a new method called "the pumping technique" to the capsule-preserving hydraulic distension for frozen shoulder. With this technique, the stretching effect can be directly applied to the joint capsule of the affected shoulder. OBJECTIVES: We attempted to evaluate the effect of capsule-preserving hydraulic distension using the pumping technique by comparing capsule-preserving hydraulic distension without it. STUDY DESIGN: A case-controlled, retrospective, comparative study. SETTING: Outpatient clinic of department of rehabilitation medicine in a single university hospital. METHODS: Patients (n = 47) with frozen shoulder who were treated with hydraulic distension were assigned into the pumping group (n = 24) and the nonpumping group (n = 23). Range of motion (ROM), Shoulder Pain and Disability Index (SPADI), and Visual Analog Scale (VAS) scores were assessed. RESULTS: Significant improvement of VAS, ROM, and SPADI scores was observed after the second injection in each group (P < 0.05). There were significant differences in total passive ROM, abduction, and flexion after the fifth injection between the 2 groups (P < 0.05). There was a significant difference in the disability domain of SPADI after the second injection between the 2 groups (P < 0.05). However, there was no significant interaction between time and group with respect to VAS scores. There were no serious complications after procedures. LIMITATIONS: This was a retrospective study. There might be some limitations in gathering comprehensive records of outcome measurements. In addition, because the objective of this study was to determine the effect of the new pumping technique, included patients range was very narrow. This study only included patients who were treated 5 times with capsule-preserving hydraulic distensions with or without the pumping technique. CONCLUSIONS: Although the effect on pain was excellent in both groups, the superiority of the new pumping technique was demonstrated by reduction of SPADI disability subscale score and improvement of ROM of the shoulder compared with the nonpumping technique. KEY WORDS: Shoulder pain, injections, stretch, exercise, ultrasonography, joint capsule, steroids, range of motion.

5.
World J Stem Cells ; 11(11): 990-1004, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31768225

RESUMO

BACKGROUND: Recently, the exclusive use of mesenchymal stem cell (MSC)-secreted molecules, called secretome, rather than cells, has been evaluated for overcoming the limitations of cell-based therapy, while maintaining its advantages. However, the use of naïve secretome may not fully satisfy the specificity of each disease. Therefore, it appears to be more advantageous to use the functionally reinforced secretome through a series of processes involving physico-chemical adjustments or genetic manipulation rather than to the use naïve secretome. AIM: To determine the therapeutic potential of the secretome released from miR-122-transfected adipose-derived stromal cells (ASCs). METHODS: We collected secretory materials released from ASCs that had been transfected with antifibrotic miR-122 (MCM) and compared their antifibrotic effects with those of the naïve secretome (CM). MCM and CM were intravenously administered to the mouse model of thioacetamide-induced liver fibrosis, and their therapeutic potentials were compared. RESULTS: MCM infusion provided higher therapeutic potential in terms of: (A) Reducing collagen content in the liver; (B) Inhibiting proinflammatory cytokines; and (C) Reducing abnormally elevated liver enzymes than the infusion of the naïve secretome. The proteomic analysis of MCM also indicated that the contents of antifibrotic proteins were significantly elevated compared to those in the naïve secretome. CONCLUSION: We could, thus, conclude that the secretome released from miR-122-transfected ASCs has higher antifibrotic and anti-inflammatory properties than the naïve secretome. Because miR-122 transfection into ASCs provides a specific way of potentiating the antifibrotic properties of ASC secretome, it could be considered as an enhanced method for reinforcing secretome effectiveness.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31752058

RESUMO

Despite the importance of brown adipocytes as a therapeutic target for the prevention and treatment of obesity, the molecular mechanism underlying brown adipocyte differentiation is not fully understood. In particular, the role of post-translational modifications in brown adipocyte differentiation has not been extensively studied. Histidine phosphorylation is increasingly recognized as one of the important protein post-translational modifications. In this study, we show that the histidine phosphorylation pattern changes during brown adipocyte differentiation. In addition, the expression level of protein histidine phosphatase 1 (PHPT1), a major mammalian phosphohistidine phosphatase, is reduced rapidly at the early phase of differentiation and recovers at the later phase. During white adipocyte differentiation in 3T3-L1, however, the expression level of PHPT1 did not significantly changed. The knockdown of PHPT1 promotes brown adipocyte differentiation, whereas the ectopic expression of PHPT1 suppresses brown adipocyte differentiation. These results collectively suggest that histidine phosphorylation is closely linked to brown adipocyte differentiation and it could be a therapeutic target for obesity and related metabolic diseases.

7.
Cell Death Dis ; 10(11): 835, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31685805

RESUMO

Ischaemic heart disease (IHD) is the leading cause of death worldwide. Although myocardial cell death plays a significant role in myocardial infarction (MI), its underlying mechanism remains to be elucidated. To understand the progression of MI and identify potential therapeutic targets, we performed tandem mass tag (TMT)-based quantitative proteomic analysis using an MI mouse model. Gene ontology (GO) analysis and gene set enrichment analysis (GSEA) revealed that the glutathione metabolic pathway and reactive oxygen species (ROS) pathway were significantly downregulated during MI. In particular, glutathione peroxidase 4 (GPX4), which protects cells from ferroptosis (an iron-dependent programme of regulated necrosis), was downregulated in the early and middle stages of MI. RNA-seq and qRT-PCR analyses suggested that GPX4 downregulation occurred at the transcriptional level. Depletion or inhibition of GPX4 using specific siRNA or the chemical inhibitor RSL3, respectively, resulted in the accumulation of lipid peroxide, leading to cell death by ferroptosis in H9c2 cardiomyoblasts. Although neonatal rat ventricular myocytes (NRVMs) were less sensitive to GPX4 inhibition than H9c2 cells, NRVMs rapidly underwent ferroptosis in response to GPX4 inhibition under cysteine deprivation. Our study suggests that downregulation of GPX4 during MI contributes to ferroptotic cell death in cardiomyocytes upon metabolic stress such as cysteine deprivation.

8.
Int J Mol Sci ; 20(22)2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31717375

RESUMO

Peroxisome proliferator activated receptor λ coactivator 1α (PGC-1α) is a potent regulator of mitochondrial biogenesis and energy metabolism. In this study, we investigated the therapeutic potential of the secretome released from the adipose-derived stem cells (ASCs) transfected with PGC-1α (PGC-secretome). We first generated PGC-1α-overexpressing ASCs by transfecting ASCs with the plasmids harboring the gene encoding PGC-1α. Secretory materials released from PGC-1α-overexpressing ASCs were collected and their therapeutic potential was determined using in vitro (thioacetamide (TAA)-treated AML12 cells) and in vivo (70% partial hepatectomized mice) models of liver injury. In the TAA-treated AML12 cells, the PGC-secretome significantly increased cell viability, promoted expression of proliferation-related markers, such as PCNA and p-STAT, and significantly reduced the levels of reactive oxygen species (ROS). In the mice, PGC-secretome injections significantly increased liver tissue expression of proliferation-related markers more than normal secretome injections did (p < 0.05). We demonstrated that the PGC-secretome does not only have higher antioxidant and anti-inflammatory properties, but also has the potential of significantly enhancing liver regeneration in both in vivo and in vitro models of liver injury. Thus, reinforcing the mitochondrial antioxidant potential by transfecting ASCs with PGC-1α could be one of the effective strategies to enhance the therapeutic potential of ASCs.

9.
J Clin Med ; 8(11)2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31694224

RESUMO

The Special Issue "Pathogenetic and Therapeutic Significance of Adipokines in Diabetes" focused on adipokines as shared diagnostic biomarkers and therapeutic targets for both obesity and type 2 diabetes. Experts discussed the pathological role of adipokines in their studies associated with diabetes. It provided new insights into the role of adipokines in diabetes. In this commentary and review, these studies will be summarized and the novel roles of adipokines will be discussed. This will also confirm the role of adipokines as biomarkers for diagnosis and prediction, and as therapeutic targets of diabetes and its related pathogenic phenomena.

10.
Regen Med ; 14(11): 1001-1012, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31726959

RESUMO

Aim: We investigated the therapeutic effects and optimal dose of human umbilical cord blood (UCB)-derived mesenchymal stem cell (MSC) injection in a chronic full-thickness rotator cuff tendon tear. Methods: Rabbits (n = 30) were allocated into three groups (normal saline, G1-Sal; 1 × 106 cells UCB-MSC, G2-Low; 2 × 106 cells UCB-MSC, G3-High). Injections were done into the chronic full-thickness rotator cuff tendon tear 6 weeks after a full-thickness tendon tear of the subscapularis was created. Gross & histologic evaluation and motion analysis was done at pre and 4 weeks post-injection. Results: There were no significant differences in tear size and motion analysis parameters 4 weeks after injection between G2-Low and G3-High. Conclusion: The benefits of UCB-MSCs are not dose-dependent in a rabbit model.

11.
World J Gastroenterol ; 25(39): 5936-5952, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31660031

RESUMO

BACKGROUND: The use of methyl-tertiary butyl ether (MTBE) to dissolve gallstones has been limited due to concerns over its toxicity and the widespread recognition of the safety of laparoscopic cholecystectomy. The adverse effects of MTBE are largely attributed to its low boiling point, resulting in a tendency to evaporate. Therefore, if there is a material with a higher boiling point and similar or higher dissolubility than MTBE, it is expected to be an attractive alternative to MTBE. AIM: To determine whether tert-amyl ethyl ether (TAEE), an MTBE analogue with a relatively higher boiling point (102 °C), could be used as an alternative to MTBE in terms of gallstone dissolubility and toxicity. METHODS: The in vitro dissolubility of MTBE and TAEE was determined by measuring the dry weights of human gallstones at predetermined time intervals after placing them in glass containers with either of the two solvents. The in vivo dissolubility was determined by comparing the weights of solvent-treated gallstones and control (dimethyl sulfoxide)-treated gallstones, after the direct infusion of each solvent into the gallbladder in both hamster models with cholesterol and pigmented gallstones. RESULTS: The in vitro results demonstrated a 24 h TAEE-dissolubility of 76.7%, 56.5% and 38.75% for cholesterol, mixed, and pigmented gallstones, respectively, which represented a 1.2-, 1.4-, and 1.3-fold increase in dissolubility compared to that of MTBE. In the in vitro experiment, the 24 h-dissolubility of TAEE was 71.7% and 63.0% for cholesterol and pigmented gallstones, respectively, which represented a 1.4- and 1.9-fold increase in dissolubility compared to that of MTBE. In addition, the results of the cell viability assay and western blot analysis indicated that TAEE had a lower toxicity towards gallbladder epithelial cells than MTBE. CONCLUSION: We demonstrated that TAEE has higher gallstone dissolubility properties and safety than those of MTBE. As such, TAEE could present an attractive alternative to MTBE if our findings regarding its efficacy and safety can be consistently reproduced in further subclinical and clinical studies.

12.
Int J Mol Sci ; 20(19)2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31590292

RESUMO

: Mitochondria play a key role in maintaining energy homeostasis in metabolic tissues, including adipose tissues. The two main types of adipose tissues are the white adipose tissue (WAT) and the brown adipose tissue (BAT). WAT primarily stores excess energy, whereas BAT is predominantly responsible for energy expenditure by non-shivering thermogenesis through the mitochondria. WAT in response to appropriate stimuli such as cold exposure and ß-adrenergic agonist undergoes browning wherein it acts as BAT, which is characterized by the presence of a higher number of mitochondria. Mitochondrial dysfunction in adipocytes has been reported to have strong correlation with metabolic diseases, including obesity and type 2 diabetes. Dysfunction of mitochondria results in detrimental effects on adipocyte differentiation, lipid metabolism, insulin sensitivity, oxidative capacity, and thermogenesis, which consequently lead to metabolic diseases. Recent studies have shown that mitochondrial function can be improved by using thiazolidinedione, mitochondria-targeted antioxidants, and dietary natural compounds; by performing exercise; and by controlling caloric restriction, thereby maintaining the metabolic homeostasis by inducing adaptive thermogenesis of BAT and browning of WAT. In this review, we focus on and summarize the molecular regulation involved in the improvement of mitochondrial function in adipose tissues so that strategies can be developed to treat metabolic diseases.

13.
Anesth Analg ; 129(3): 864-873, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31425231

RESUMO

BACKGROUND: As national opioid consumption in South Korea has soared, well-validated screening tools for opioid use disorder (OUD) have become indispensable. The aims of our study were to evaluate OUD using the Korean version of the CAGE-Adapted to Include Drugs (CAGE-AID) and the CAGE-Opioid (an alternative version of the CAGE-AID), and to investigate clinical predictors that might be useful to screen for OUD in conjunction with the CAGE-AID/Opioid questionnaires. METHODS: A single-center, prospective, observational study was performed. After linguistic validation of the Korean version of the CAGE-AID/Opioid questionnaires, we assessed OUD in patients with chronic opioid treatment. Multivariable logistic models of the CAGE-AID/Opioid questionnaires combined with relevant clinical predictors were established. Then, the receiver operating characteristic curve analysis of the multivariable CAGE-AID/Opioid models was conducted to assess diagnostic accuracy to screen for OUD. Next, we calculated predicted probability with >85% sensitivity and >50% specificity in each CAGE-AID and CAGE-Opioid model. Using the optimal value of the predicted probability, a cutoff score of the CAGE-AID/Opioid questionnaires combined with the relevant clinical factors was suggested to screen for OUD. RESULTS: Among 201 participants, 51 patients showed ≥1 OUDs. In the multivariable regression model, male sex, comorbid neuropsychiatric disorder, and current heavy drinking significantly remained as clinical variables to predict OUD combined with the scores of the Korean CAGE-AID/Opioid questionnaire. The area under the curve was 0.77 (95% confidence interval, 0.71-0.83) for the CAGE-AID model and 0.78 (95% confidence interval, 0.71-0.83) for the CAGE-Opioid model. The optimal predicted probability values to screen for OUD in the CAGE-AID/Opioid models were >0.135 (sensitivity, 0.86; specificity, 0.52) and >0.142 (sensitivity, 0.86; specificity, 0.53), respectively. When we used these predictive probabilities, the cutoff score of the CAGE-AID/Opioid questionnaires ranged from 0 to 3, which was dependent on the presence of the relevant clinical variables in each model. CONCLUSIONS: In this study, one fourth of the total participants with chronic opioid treatment showed OUD in the Korean population. The multivariable models of the CAGE-AID/Opioid with sex, comorbid neuropsychiatric disorder, and current heavy drinking are valid parameters to screen for OUD, with the cutoff scores of the CAGE-AID/Opioid questionnaires ranging from 0 to 3 depending on the presence of the clinical variables.

14.
PLoS Biol ; 17(7): e3000367, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31323018

RESUMO

Human papillomaviruses (HPVs) are causative agents of various diseases associated with cellular hyperproliferation, including cervical cancer, one of the most prevalent tumors in women. E7 is one of the two HPV-encoded oncoproteins and directs recruitment and subsequent degradation of tumor-suppressive proteins such as retinoblastoma protein (pRb) via its LxCxE motif. E7 also triggers tumorigenesis in a pRb-independent pathway through its C-terminal domain, which has yet been largely undetermined, with a lack of structural information in a complex form with a host protein. Herein, we present the crystal structure of the E7 C-terminal domain of HPV18 belonging to the high-risk HPV genotypes bound to the catalytic domain of human nonreceptor-type protein tyrosine phosphatase 14 (PTPN14). They interact directly and potently with each other, with a dissociation constant of 18.2 nM. Ensuing structural analysis revealed the molecular basis of the PTPN14-binding specificity of E7 over other protein tyrosine phosphatases and also led to the identification of PTPN21 as a direct interacting partner of E7. Disruption of HPV18 E7 binding to PTPN14 by structure-based mutagenesis impaired E7's ability to promote keratinocyte proliferation and migration. Likewise, E7 binding-defective PTPN14 was resistant for degradation via proteasome, and it was much more effective than wild-type PTPN14 in attenuating the activity of downstream effectors of Hippo signaling and negatively regulating cell proliferation, migration, and invasion when examined in HPV18-positive HeLa cells. These results therefore demonstrated the significance and therapeutic potential of the intermolecular interaction between HPV E7 and host PTPN14 in HPV-mediated cell transformation and tumorigenesis.


Assuntos
Transformação Celular Neoplásica , Proteínas de Ligação a DNA/metabolismo , Proteínas Oncogênicas Virais/metabolismo , Proteínas Tirosina Fosfatases não Receptoras/metabolismo , Neoplasias do Colo do Útero/metabolismo , Sequência de Aminoácidos , Linhagem Celular , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Feminino , Células HEK293 , Células HeLa , Humanos , Modelos Moleculares , Proteínas Oncogênicas Virais/química , Proteínas Oncogênicas Virais/genética , Ligação Proteica , Domínios Proteicos , Proteínas Tirosina Fosfatases não Receptoras/química , Proteínas Tirosina Fosfatases não Receptoras/genética , Proteína do Retinoblastoma/química , Proteína do Retinoblastoma/genética , Proteína do Retinoblastoma/metabolismo , Homologia de Sequência de Aminoácidos , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia
15.
Allergy Asthma Immunol Res ; 11(5): 723-735, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31332982

RESUMO

PURPOSE: To investigate the causative allergens and clinical characteristics of Korean adult patients with food allergy (FA). METHODS: This retrospective, cross-sectional single-institutional study enrolled Korean adult patients (n = 812) suspected of having FA. For diagnosis, causality assessment history taking, ImmunoCAP specific immunoglobulin E measurement and/or skin prick test were performed. RESULTS: Among 812 patients, 415 were diagnosed as having FA. The most common causative allergen was fruit, with a diagnosis of pollen food allergy syndrome (PFAS: 155, 37.3%), followed by crustaceans (111, 26.7%), wheat (63, 15.1%), fruits in patients without PFAS(43, 10.3%), buckwheat (31, 7.4%), peanut (31, 7.4%), walnut (25, 6.0%), red meat due to reaction to galactose-α-1,3-galactose (α-Gal) (8, 1.9%), and silkworm pupa (13, 3.1%). Allergy to egg, milk, fish, or shellfish was rare in Korean adults. One-third of patients with FA exhibited multiple FAs (238/415, 57.3%); the average number of causative allergens was 2.39. About 129 patients (31.0%) were diagnosed as having anaphylaxis; in these patients, wheat was the most frequent causative food. Twenty patients were further diagnosed with food-dependent exercise-induced anaphylaxis (FDEIA); all were due to wheat. In particular, crustaceans, wheat, PFAS, buckwheat, and red meat (α-Gal) were also frequent causes of anaphylaxis. CONCLUSIONS: Wheat, fruits with or without PFAS, and crustaceans are important and frequent causative allergens in Korean adult FA; these allergens differ from those found in childhood FA. It is notable that non-classic allergies, such as PFAS, FDEIA, and α-Gal allergy, are the important causes of anaphylaxis in Korean adult FA.

16.
J Transl Med ; 17(1): 195, 2019 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-31182117

RESUMO

BACKGROUND: Although methyl-tertiary butyl ether (MTBE) is the only clinical topical agent for gallstone dissolution, its use is limited by its side effects mostly arising from a relatively low boiling point (55 °C). In this study, we developed the gallstone-dissolving compound containing an aromatic moiety, named 2-methoxy-6-methylpyridine (MMP) with higher boiling point (156 °C), and compared its effectiveness and toxicities with MTBE. METHODS: The dissolubility of MTBE and MMP in vitro was determined by placing human gallstones in glass containers with either solvent and, then, measuring their dry weights. Their dissolubility in vivo was determined by comparing the weights of solvent-treated gallstones and control (dimethyl sulfoxide)-treated gallstones, after directly injecting each solvent into the gallbladder in hamster models with cholesterol and pigmented gallstones. RESULTS: In the in vitro dissolution test, MMP demonstrated statistically higher dissolubility than did MTBE for cholesterol and pigmented gallstones (88.2% vs. 65.7%, 50.8% vs. 29.0%, respectively; P < 0.05). In the in vivo experiments, MMP exhibited 59.0% and 54.3% dissolubility for cholesterol and pigmented gallstones, respectively, which were significantly higher than those of MTBE (50.0% and 32.0%, respectively; P < 0.05). The immunohistochemical stains of gallbladder specimens obtained from the MMP-treated hamsters demonstrated that MMP did not significantly increase the expression of cleaved caspase 9 or significantly decrease the expression of proliferation cell nuclear antigen. CONCLUSIONS: This study demonstrated that MMP has better potential than does MTBE in dissolving gallstones, especially pigmented gallstones, while resulting in lesser toxicities.

17.
Spine J ; 19(9): 1478-1489, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31201860

RESUMO

BACKGROUND CONTEXT: Lumbosacral disc herniation (LDH) is one of the most frequent musculoskeletal diseases causative of sick leave in the workplace and morbidity in daily activities. Nonsurgical managements are considered as first line treatment before surgical treatment. PURPOSE: This clinical practice guideline (CPG) is intended to provide physicians who treat patients diagnosed with LDH with a guideline supported by scientific evidence to assist in decision-making for appropriate and reasonable treatments. STUDY DESIGN/SETTING: A systematic review. PATIENT SAMPLE: Studies of human subjects written in Korean or English that met the following criteria were selected: patients aged ≥18 years, clinical presentation of low back and radicular leg pain, diagnosis of LDH on radiological evaluation including computed tomography or magnetic resonance imaging. OUTCOMES MEASURES: Pain and functional evaluation scales such as visual analogue scale, numeric rating scale, and Oswestry disability index METHODS: The MEDLINE (PubMed), EMBASE, Cochrane Review, and KoreaMed databases were searched for articles regarding non-surgical treatments for LDH published up to July 2017. Of the studies fulfilling these criteria, those investigating clinical results after non-surgical treatment including physical and behavioral therapy, medication, and interventional treatment in terms of pain control and functional improvements were chosen for this study. RESULTS: Nonsurgical treatments were determined to be clinically effective with regards to pain reduction and functional improvement in patients with LDH. Nevertheless, the evidence level was generally not evaluated as high degree, which might be attributed to the paucity of well-designed randomized controlled trials. Exercise and traction were strongly recommended despite moderate level of evidence. Epidural injection was strongly recommended with high degree of evidence and transforaminal approach was more strongly recommended than caudal approach. CONCLUSIONS: This CPG provides new and updated evidence-based recommendations for treatment of the patients with LDH, which suggested that, despite an absence of high degrees of evidence level, non-surgical treatments were clinically effective.

18.
Medicine (Baltimore) ; 98(19): e15506, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31083191

RESUMO

Intra-articular hyaluronic acid (HA) is widely used to treat symptomatic osteoarthritis (OA) in the carpometacarpal joint (CMCJ) of the thumb. However, although apparently effective and relatively safe, intra-articular HA injections act relatively slowly. Therefore, a nonsteroidal anti-inflammatory drug could be added for more prompt pain relief. The aim of this study was to compare the efficacy and safety of ultrasound (US)-guided intra-articular injection of HA and ketorolac with that of HA alone in patients with OA of the CMCJ of the thumb.Seventy-four patients identified by chart review to have a diagnosis of OA of the CMCJ of the thumb received either a US-guided intra-articular injection of 0.5 mL of sodium hyaluronate and 0.5 mL of ketorolac (n = 38) or 0.5 mL of sodium hyaluronate and 0.5 mL of saline (n = 36). Disabilities of the arm, shoulder, and hand (DASH) and verbal numeric scale (VNS) pain scores were recorded before and 1, 3, and 6 months after injection. Univariable analyses (using the chi-squared test) and multiple logistic regression analysis were performed to evaluate the relationship between potential predictors of the outcome (treatment allocation, patient age and sex, duration of pain, and Eaton-Littler classification) and therapeutic effects.The DASH and VNS scores were improved at 1, 3, and 6 months postinjection in both groups. The onset of pain relief was significantly more rapid (at 1 month) after the injection containing HA and ketorolac than after the injection containing HA alone. In 55.3% of cases, pain and function were improved postinjection compared with baseline and remained so for up to 6 months. The success rate was not significantly different between the assessments at 1, 3, and 6 months, and the univariable analyses did not identify any statistically significant potential predictors of the outcome. Multiple logistic regression analysis did not identify any independent predictors of a successful outcome at midterm follow-up.The onset of analgesic action was more rapid after an injection containing HA and ketorolac than after 1 containing HA alone in patients with OA of the CMCJ of the thumb. There were no serious complications.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Articulações Carpometacarpais , Ácido Hialurônico/administração & dosagem , Cetorolaco/administração & dosagem , Osteoartrite/tratamento farmacológico , Viscossuplementos/administração & dosagem , Idoso , Feminino , Humanos , Injeções Intra-Articulares , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Polegar , Ultrassonografia de Intervenção
19.
Clin Neuropharmacol ; 42(3): 73-76, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31085946

RESUMO

OBJECTIVES: Central poststroke pain (CPSP) is the neuropathic pain in areas of the body corresponding to stroke lesions. It is often refractory to treatment, reduces quality of life, and impedes rehabilitation. The pharmacological treatment of CPSP is challenging. Duloxetine, a serotonin-norepinephrine reuptake inhibitor, is known to be effective against neuropathic pain. The current study describes the efficacy of duloxetine in reducing pain severity in CPSP patients. SUBJECTS AND METHODS: For the purpose of this study, CPSP was defined as spontaneous pain within an area of the body corresponding to the brain lesion that emerged at or after stroke onset. Any previously prescribed medical therapy for the patients was not changed or stopped; duloxetine 30 mg was added to their ongoing treatment. Pain was assessed at baseline and thereafter at 1 and 3 weeks using Numeric Rating Scale (NRS) and Short-form MC Gill Pain Questionnaire scores. At the first follow-up, scores were reviewed and dose was doubled if no improvement or adverse effects were observed. RESULTS: From a total of 37 patients, 4 were withdrawn because of adverse effects including nausea, agitation, and somnolence. The mean elapsed time of observed symptoms since stroke onset was 3.1 ± 4.1 years. There was a significant difference between the mean values of Short-form MC Gill Pain Questionnaire and NRS scores at baseline and those at the follow-up assessment. Twenty-six (70.3%) of the patients showed at least 30% reduction of NRS compared with baseline at the third week. CONCLUSIONS: Our findings suggest that duloxetine can be effective for managing CPSP.


Assuntos
Analgésicos/uso terapêutico , Dor Crônica/tratamento farmacológico , Dor Crônica/etiologia , Cloridrato de Duloxetina/uso terapêutico , Acidente Vascular Cerebral/complicações , Idoso , Dor Crônica/diagnóstico por imagem , Feminino , Seguimentos , Lateralidade Funcional/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Retrospectivos , Resultado do Tratamento
20.
J Tissue Eng Regen Med ; 13(6): 1071-1078, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30964964

RESUMO

The purpose of this study is to evaluate the effect of extracorporeal shock wave therapy (ESWT) according to treatment timing in rabbits with 10% dextrose-induced carpal tunnel syndrome (CTS); 0.1-ml 10% dextrose solution was injected under ultrasound guidance twice weekly to the left forepaw subsynovial connective tissue (SSCT) within the carpal tunnel of 36 New Zealand white rabbits to induce CTS. The rabbits were randomly allocated into four groups: G1-S (sham ESWT), G2-E4 (ESWT at 4 weeks), G3-E8 (at 8 weeks), and G4-E16 (at 16 weeks). Radial ESWT (500 pulses, 0.08 mJ/mm2 , 2 Hz) was repeated thrice weekly. Median nerve distal motor latency (DML) was measured before injection and at 4, 8, 12, 16, and 20 weeks after the first injection. All rabbits were sacrificed 20 weeks after injection. The median nerve cross-sectional area (CSA) and SSCT thickness were measured with light microscopy. The mean median nerve DML at 4 weeks after the first dextrose injection did not differ from that at preinjection in all groups. The mean median nerve DML significantly increased before ESWT in all groups (p < .05); however, it did not increase in G2-E4 and G3-E8 for 12 weeks after ESWT and in G4-E16 for 4 weeks (p > .05). Mean CSA of the median nerve and mean SSCT thickness in G2-E4 were significantly lower than those in the other groups (p < .05). ESWT may prevent the progression of CTS for 12 weeks in rabbits with dextrose-induced CTS regardless of treatment timing, and early application results in superior outcomes.

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