ABSTRACT
UNLABELLED: Temporomandibular disorders (TMD) are a significant public health problem, affecting approximately 5-12% of the population. OBJECTIVES: This retrospective cross-sectional study investigated the relationship between 8 AM serum cortisol levels (8ASC) and disc displacement disorders (DDD) of TMD. One hundred and forty patients with DDD were recruited. Among them, 60 patients comprised the case group of disc displacement without reduction with limited opening (DDWORWLO, age 37·7 ± 17·22), and 80 were 'other DDD' for the control group (age 36·4 ± 13·08). The independent variables included domains of demography, history, malocclusion, comorbid symptoms, comorbid TMD and 8ASC. Data were analysed with the chi-square test, logistic regression and receiver operating characteristic (ROC) curve. Results of multiple logistic regression showed that 8ASC was the only factor significantly related to DDWORWLO (P = 0·006). Receiver operating characteristic analysis of DDWORWLO and 8ASC indicated an area under the curve of 0·669, standard error of 0·049 and P value of 0·001. The adequate cut-off point of 8ASC was 12·45 (µg dL(-1) ), with sensitivity of 0·636, and specificity of 0·729. 8 AM serum cortisol level can be used as a clinical clue to differentiate DDWORWLO from other DDD.
Subject(s)
Hydrocortisone/blood , Temporomandibular Joint Disc/physiopathology , Temporomandibular Joint Disorders/diagnosis , Adult , Biomarkers/blood , Cross-Sectional Studies , Female , Humans , Male , ROC Curve , Retrospective Studies , Temporomandibular Joint Disorders/blood , Temporomandibular Joint Disorders/physiopathologyABSTRACT
BACKGROUND AND PURPOSE: Earlier studies suggested an association between idiopathic restless legs syndrome (RLS) and cardiovascular diseases. However, the risk of cardiovascular events in patients with secondary RLS due to end-stage renal disease (ESRD) is unclear. Our aim was to examine whether ESRD patients with RLS had an increased risk of cardio/cerebrovascular events and mortality. METHODS: In all, 1093 ESRD patients were recruited between 2009 and 2010. The diagnosis and severity of RLS were assessed in a face-to-face interview. The occurrence of cardio/cerebrovascular events and death were confirmed by medical record review. The association between RLS and the outcomes of interest was examined using an adjusted multivariate Cox regression model. RESULTS: After a mean follow-up period of 3.7 ± 0.8 years, ESRD patients with RLS had a significantly higher risk of developing cardiovascular events and strokes [adjusted hazard ratio (aHR) 2.82, 95% confidence interval (CI) 2.02-4.11, and aHR 2.41, 95% CI 1.55-3.75, respectively] compared with patients without RLS. Increasing RLS severity was associated with an increasing likelihood of cardiovascular events [mild RLS severity, aHR 1.71 (95% CI 1.02-2.87); moderate, 2.79 (1.64-4.66); severe, 2.85 (1.99-4.46)] and strokes [mild, 1.89 (0.87-4.16); moderate, 2.42 (1.50-3.90); severe, 2.64 (1.49-4.91)] in a dose-dependent manner. RLS also increased the risk of total mortality in patients with ESRD [aHR 1.53 (95% CI 1.07-2.18), P = 0.02]; this association attenuated slightly after stratification by individual RLS severity category [mild RLS severity, aHR 1.44 (95% CI 0.78-2.67); moderate, 1.49 (0.98-2.55); severe, 2.03 (0.93-4.45)]. CONCLUSIONS: ESRD patients with RLS demonstrated an increased likelihood of cardio/cerebrovascular events and mortality.
Subject(s)
Cardiovascular Diseases/epidemiology , Kidney Failure, Chronic/epidemiology , Restless Legs Syndrome/epidemiology , Aged , Cardiovascular Diseases/mortality , Cerebrovascular Disorders/epidemiology , Cerebrovascular Disorders/mortality , Comorbidity , Female , Humans , Kidney Failure, Chronic/complications , Male , Middle Aged , Restless Legs Syndrome/etiology , Severity of Illness IndexABSTRACT
Macrophage migration inhibitory factor (MIF), a pleiotropic cytokine, plays an important role in the pathogenesis of atrial fibrillation; however, the upstream regulation of MIF in atrial myocytes remains unclear. In the present study, we investigated whether and how MIF is regulated in response to the renin-angiotensin system and oxidative stress in atrium myocytes (HL-1 cells). MIF protein and mRNA levels in HL-1 cells were assayed using immunofluorescence, real-time PCR, and Western blot. The result indicated that MIF was expressed in the cytoplasm of HL-1 cells. Hydrogen peroxide (H2O2), but not angiotensin II, stimulated MIF expression in HL-1 cells. H2O2-induced MIF protein and gene levels increased in a dose-dependent manner and were completely abolished in the presence of catalase. H2O2-induced MIF production was completely inhibited by tyrosine kinase inhibitors genistein and PP1, as well as by protein kinase C (PKC) inhibitor GF109203X, suggesting that redox-sensitive MIF production is mediated through tyrosine kinase and PKC-dependent mechanisms in HL-1 cells. These results suggest that MIF is upregulated by HL-1 cells in response to redox stress, probably by the activation of Src and PKC.
Subject(s)
Animals , Mice , Hydrogen Peroxide/pharmacology , Intramolecular Oxidoreductases/drug effects , Macrophage Migration-Inhibitory Factors/drug effects , Myocytes, Cardiac/metabolism , Oxidants/pharmacology , Protein Kinase C/metabolism , src-Family Kinases/metabolism , Angiotensin II/metabolism , Blotting, Western , Cell Line , Immunohistochemistry , Intramolecular Oxidoreductases/genetics , Microscopy, Confocal , Macrophage Migration-Inhibitory Factors/genetics , Oxidative Stress/physiology , Protein Kinase Inhibitors/pharmacology , Real-Time Polymerase Chain Reaction , Renin-Angiotensin System/physiologyABSTRACT
S-nitrosoglutathione (GSNO) has been reported to protect against ischemic brain injury, however, the underlying mechanisms remain to be elucidated. In the present study, we aimed to investigate the effects of GSNO pre-treatment on the S-nitrosylation of Fas and subsequent events in the Fas pathway, and reveal the correlation between Fas S-nitrosylation and nNOS activation in the rat hippocampal CA1 region after global cerebral ischemia. The results showed that GSNO pre-treatment not only facilitated the survival of hippocampal CA1 pyramidal neurons, but also abolished the activation of pro-apoptotic Caspase-8, Bid, Caspase-9 and Caspase-3. The S-nitrosylation of Fas increased sustainedly after global ischemia, and GSNO blocked such an increase. Global cerebral ischemia/reperfusion promoted the binding between neuronal nitric oxide synthase (nNOS) and postsynaptic density protein 95 that has been reported to activate nNOS, and GSNO inhibited the post-ischemic nNOS activation and NO release. A selective nNOS inhibitor 7-nitroindazole diminished the ischemia/reperfusion-induced Fas S-nitrosylation, suggesting a critical role of endogenous NO from nNOS activation in Fas S-nitrosylation. In addition, pre-administration of GSNO decreased the translocation of Fas to membrane, the formation of CD95(hi) on the membrane, the internalization of Fas aggregates to plasma, as well as the assembly of DISC/hiDISC. These results indicate that GSNO-induced nNOS inactivation associates with the down-regulation of Fas S-nitrosylation and consequent Fas signal cascade, which is responsible for the GSNO-mediated neuronal survival after brain ischemia. The understanding of GSNO neuroprotection provides a novel strategy to find potential therapeutic targets for ischemic stroke.
Subject(s)
Brain Ischemia/drug therapy , CA1 Region, Hippocampal/drug effects , Down-Regulation/drug effects , Fas Ligand Protein/metabolism , Neuroprotective Agents/pharmacology , S-Nitrosoglutathione/pharmacology , Signal Transduction/drug effects , Animals , Brain Ischemia/metabolism , CA1 Region, Hippocampal/cytology , CA1 Region, Hippocampal/metabolism , Caspase 3/metabolism , Caspase 8/metabolism , Caspase 9/metabolism , Disease Models, Animal , Indazoles/pharmacology , Male , Neurons/drug effects , Neurons/metabolism , Nitric Oxide Synthase Type I/antagonists & inhibitors , Nitric Oxide Synthase Type I/metabolism , Protein Processing, Post-Translational , Rats , Rats, Sprague-Dawley , Reperfusion Injury/drug therapy , Reperfusion Injury/metabolism , fas Receptor/metabolismABSTRACT
BACKGROUND AND PURPOSE: Restless legs syndrome (RLS) is an underestimated movement disorder in patients with end-stage renal disease (ESRD). Several clinical and laboratory factors were inconsistently reported to associate with RLS. We aim to perform a large-scale multicenter study to investigate the possible associated risk factors of RLS in patients with ESRD in Taiwan, a country with the highest incidence of uremia in the world. METHODS: From October 2009 to October 2011, we constitutively recruited 1130 patients with ESRD from 17 hemodialysis centers. Demographic, laboratory data, presence and severity of RLS were collected. Odds ratios (ORs) were estimated by logistic regression models. RESULTS: We found the prevalence of RLS to be 25.3% in patients with ESRD. Having type 2 diabetes [ORâ =â 3.61 (2.27-5.77), Pâ <â 0.01], low serum transferrin saturation [ORâ =â 1.42 (1.01-2.03), Pâ <â 0.05] and duration of dialysis [ORâ =â 1.09 (1.03-1.14), Pâ <â 0.01] were associated with RLS. In contrast, high serum hemoglobin level was inversely associated with RLS [ORâ =â 0.61 (0.40-0.89), Pâ <â 0.05]. RLS has a significant impact on sleep quality in dialysis patients. Among patients with RLS, history of type 2 diabetes [ORâ =â 4.04 (1.65-10.79), Pâ <â 0.05], low serum hemoglobin level [ORâ =â 5.41 (2.43-13.12), Pâ <â 0.01] and duration of dialysis [ORâ =â 1.01 (1.01-1.02), Pâ <â 0.01] were associated with increased severity of RLS. CONCLUSIONS: Our findings demonstrated that RLS is common in Taiwanese dialysis patients. Clinicians should have a high suspicion for the presence of RLS symptoms in patients with ESRD, especially those with type 2 diabetes, anemia, low serum iron status and long duration of dialysis.
Subject(s)
Kidney Failure, Chronic/epidemiology , Restless Legs Syndrome/epidemiology , Female , Humans , Kidney Failure, Chronic/complications , Male , Middle Aged , Prevalence , Renal Dialysis/statistics & numerical data , Restless Legs Syndrome/complications , Risk Factors , Taiwan/epidemiologyABSTRACT
MBD is a rare disorder strongly associated with alcoholism. It is characterized pathologically by demyelination and necrosis of the corpus callosum. MBD presents with severe neurologic deficits and significant sequelae developing in most survivors. We report a patient with total clinical recovery. Serial MR imaging demonstrated typical lesions with restricted diffusion in the acute stage and total resolution without atrophy or cystic change.
Subject(s)
Alcoholism/pathology , Magnetic Resonance Imaging , Marchiafava-Bignami Disease/pathology , Recovery of Function , Cerebellum/pathology , Corpus Callosum/pathology , Humans , Internal Capsule/pathology , Male , Middle Aged , Remission, SpontaneousABSTRACT
BACKGROUND AND PURPOSE: The transcription factor nuclear factor-kappaB (NF-kappaB) has been linked to the cell growth, apoptosis and cell cycle progression. NF-kappaB blockade induces apoptosis of cancer cells. Therefore, NF-kappaB is suggested as a potential therapeutic target for cancer. Here, we have evaluated the anti-cancer potential of a novel NF-kappaB inhibitor, quinoclamine (2-amino-3-chloro-1,4-naphthoquinone). EXPERIMENTAL APPROACH: In a large-scale screening test, we found that quinoclamine was a novel NF-kappaB inhibitor. The global transcriptional profiling of quinoclamine in HepG2 cells was therefore analysed by transcriptomic tools in this study. KEY RESULTS: Quinoclamine suppressed endogenous NF-kappaB activity in HepG2 cells through the inhibition of IkappaB-alpha phosphorylation and p65 translocation. Quinoclamine also inhibited induced NF-kappaB activities in lung and breast cancer cell lines. Quinoclamine-regulated genes interacted with NF-kappaB or its downstream genes by network analysis. Quinoclamine affected the expression levels of genes involved in cell cycle or apoptosis, suggesting that quinoclamine exhibited anti-cancer potential. Furthermore, quinoclamine down-regulated the expressions of UDP glucuronosyltransferase genes involved in phase II drug metabolism, suggesting that quinoclamine might interfere with drug metabolism by slowing down the excretion of drugs. CONCLUSION AND IMPLICATIONS: This study provides a comprehensive evaluation of quinoclamine by transcriptomic analysis. Our findings suggest that quinoclamine is a novel NF-kappaB inhibitor with anti-cancer potential.
Subject(s)
Antineoplastic Agents/pharmacology , Gene Expression Profiling , NF-kappa B/antagonists & inhibitors , Naphthoquinones/pharmacology , Apoptosis/drug effects , Apoptosis/genetics , Cell Cycle/drug effects , Cell Cycle/genetics , Cell Line, Tumor , Cell Survival/drug effects , Dose-Response Relationship, Drug , Gene Expression Profiling/methods , Gene Expression Regulation/drug effects , Gene Regulatory Networks , Glucuronosyltransferase/genetics , Humans , I-kappa B Proteins/metabolism , NF-KappaB Inhibitor alpha , NF-kappa B/genetics , NF-kappa B/metabolism , Oligonucleotide Array Sequence Analysis , Phosphorylation , Protein Transport , Transcription Factor RelA/metabolism , TransfectionSubject(s)
Motor Skills Disorders/drug therapy , Myelinolysis, Central Pontine/drug therapy , Pyridines/therapeutic use , Speech Disorders/drug therapy , Alcoholism/complications , Alcoholism/drug therapy , Female , Humans , Middle Aged , Motor Skills Disorders/etiology , Myelinolysis, Central Pontine/complications , Pyridines/pharmacology , Speech/drug effects , Speech/physiology , Speech Disorders/etiology , ZolpidemABSTRACT
UNLABELLED: Our aim was to study the effect of resveratrol on the expressions of protein kinase C isotypes (PKC alpha, theta) in peripheral blood lymphocytes and on the expression of IkappaB kinase-beta (IKK beta) in lymphocytes in allografts in a rat liver transplantation model. METHODS: Orthotopic liver transplantations (OLT) were performed from Sprague Dawley rats to Wistar rats. The recipients were divided into two groups after OLT. In the RES group, resveratrol was given intraperitoneally once a day (100 mg kg(-1)) after OLT, whereas in the control group vehicle buffer was given. The expressions of PKC alpha, theta in peripheral blood lymphocytes, expression of IKK beta in lymphocytes in allograft, and survival periods were compared between the groups. RESULTS: The mean survival period after OLT in the RES group was significantly longer than that in control group (P < .05). On posttransplant day 7, the expression of PKC theta in peripheral blood lymphocytes in the RES group was significantly decreased compared with that in the control group (P < .05), whereas there was no obvious difference in the expressions of PKC alpha between the two groups (P > .05), and the positive rate of IKK beta protein in lymphocytes in allografts in RES group was significantly decreased compared with that in the control group (P < .05). CONCLUSION: Resveratrol showed an immunosuppressive effect on lymphocytes for allograft rejection in the rat. Down-regulation of the expression of PKC theta in peripheral blood lymphocytes may be part of the mechanism.
Subject(s)
Isoenzymes/genetics , Liver Transplantation/physiology , Protein Kinase C/genetics , Stilbenes/therapeutic use , T-Lymphocytes/enzymology , Animals , Gene Expression Regulation, Enzymologic/drug effects , Male , Models, Animal , Protein Kinase C-theta , Rats , Rats, Sprague-Dawley , Rats, Wistar , Resveratrol , Reverse Transcriptase Polymerase Chain Reaction , T-Lymphocytes/drug effects , Vasodilator Agents/therapeutic useABSTRACT
This report is about a rare case of a lumbar spinal dural arteriovenous fistula (DAVF) with distant brainstem symptoms of vertigo and ataxia. Brain magnetic resonance imaging (MRI) demonstrated a high signal abnormality in the lower pons, medulla, and cervico-medullary junction, presumably related to venous hypertension. Spinal MRI revealed markedly dilated veins along the dorsal aspect of the cord, while spinal angiography confirmed the presence of a lumbar spinal DAVF. Because lumbar DAVF may cause remote brainstem symptoms, spinal DAVF should be considered in the differential diagnosis of high signal MRI abnormalities localized in the brainstem. Properly extending the scanning range is essential in the diagnosis.
Subject(s)
Arteriovenous Fistula/diagnosis , Magnetic Resonance Imaging , Aged , Angiography , Arteriovenous Fistula/complications , Ataxia/etiology , Diagnosis, Differential , Dura Mater/blood supply , Fatal Outcome , Humans , Lumbosacral Region/blood supply , Male , Vertigo/etiologyABSTRACT
Interleukin (IL)-1 is markedly overexpressed in the brains of patients with Alzheimer's disease (AD). We aimed to evaluate the relationship between three polymorphisms of the IL1 gene (IL-1beta promoter -511T/C, IL-1beta exon 5 E1/E2 and IL-1-RA) and late onset AD in Taiwan Chinese. Forty-six late onset AD patients and 103 unrelated, age-matched, healthy controls living in the same area were included. PCR was used to resolve the two IL-1beta polymorphisms and the IL-1Ra intron 2 polymorphism. The -511T/T type of the IL-1beta promoter (unlike IL-1beta exon 5 and IL-1-RA) was more frequently found in AD than in healthy patients (-511C/C type versus T/T type, OR = 0.944, CI = 0.393, 2.269, P = 0.898; -511C/T type versus T/T type, OR = 0.375, CI = 0.156, 0.902, P = 0.028). The -511T/T genotype (unlike the other two polymorphisms) is a marker demonstrating that late onset AD in Chinese patients in Taiwan is genetically determined.
Subject(s)
Alzheimer Disease/genetics , Genetic Predisposition to Disease , Interleukin-1/genetics , Polymorphism, Genetic , Aged , Case-Control Studies , Confidence Intervals , DNA Mutational Analysis/methods , Female , Gene Frequency , Genotype , Humans , Male , Odds Ratio , RNA, Messenger/biosynthesis , Reverse Transcriptase Polymerase Chain Reaction/methods , Taiwan/ethnologyABSTRACT
OBJECTIVE: The literature on resveratrol in severe acute pancreatitis (SAP) is limited though it has been widely studied in infections and trauma. The aim of this study was to investigate the inhibitory effect of resveratrol on inflammatory responses in a rat model of SAP. METHODS: Male Sprague-Dawley (SD) rats were randomly divided into 3 groups: SAP group, resveratrol group and control group. 4.0% sodium taurocholate was injected into the pancreatic duct to induce SAP. In the resveratrol group, resveratrol (10 mg/kg) was injected through penal vein 5 min after SAP was induced. The peritoneal macrophages of the rats were collected 3, 6 and 12 h after stimulus and then incubated for 24 h. The expression of nuclear factor kappa B (NF-kappaB) and inducible nitric oxide synthase (iNOS) in peritoneal macrophages was measured. The levels of tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1) and nitric oxide (NO) in culture medium of peritoneal macrophages and serum of rats were evaluated. RESULTS: Histological examination of pancreas indicated that the damage in the SAP group was more severe than that in the resveratrol group. The expression of NF-kappaB and iNOS in peritoneal macrophages was significantly higher in the SAP group than in the resveratrol group. The concentrations of TNF-alpha, IL-1 and NO in culture medium and serum were significantly elevated in the SAP group when compared with the resveratrol group. CONCLUSIONS: The inhibiting effect on the inflammatory response and the decreased expression of TNF-alpha, IL-1 and NO in peritoneal macrophages suggest resveratrol as a novel anti-inflammatory agent for reducing the severity of SAP.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Macrophages, Peritoneal/drug effects , Pancreatitis/metabolism , Pancreatitis/pathology , Stilbenes/pharmacology , Acute Disease , Animals , Culture Media/chemistry , Disease Models, Animal , Interleukin-1/analysis , Interleukin-1/blood , Macrophages, Peritoneal/metabolism , Male , NF-kappa B/metabolism , Nitric Oxide/analysis , Nitric Oxide/blood , Nitric Oxide Synthase/metabolism , Random Allocation , Rats , Rats, Sprague-Dawley , Resveratrol , Systemic Inflammatory Response Syndrome/metabolism , Systemic Inflammatory Response Syndrome/pathology , Time Factors , Tumor Necrosis Factor-alpha/analysis , Tumor Necrosis Factor-alpha/metabolismABSTRACT
BACKGROUND: Prostacyclin mediates, at least partly, the splanchnic vascular hyporesponsiveness to glypressin in bleeding portal hypertensive rats. This study investigated the relative contribution of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in the splanchnic hyposensitivity to glypressin in rats with portal hypertension induced by partial portal vein ligation (PVL). METHODS: Fourteen days after the operation, the rats were divided into without- and with-bleeding groups. Three series of PVL rats were used to investigate (i). the haemodynamic effects of glypressin (0.07 mg x kg(-1) intravenously), (ii). COX-1/COX-2 mRNA expression over abdominal aorta and superior mesenteric artery and (iii). plasma levels of 6-keto-prostaglandin-F1alpha. In rats with a hypotensive haemorrhage, 4.5 mL of blood was withdrawn and 50% of the withdrawn blood was re-infused before blood and vessel sampling or the administration of glypressin. RESULTS: Splanchnic hyposensitivity to glypressin was demonstrated in the haemorrhage-transfused PVL rats with enhanced COX-1 expression of superior mesenteric artery and increased plasma levels of 6-keto-prostaglandin-F1alpha. There were no differences in the COX-2 expression of superior mesenteric artery and COX-1 and COX-2 expressions of abdominal aorta between without- and with-bleeding groups. CONCLUSION: In portal hypertensive rats with acute haemorrhage, COX-1 over-expression in the superior mesenteric artery plays a role in mediating the splanchnic hyposensitivity to glypressin.