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The incidence of secondary systemic fungal infections has sharply increased in bacterial septic patients. Antimycotics exhibit immunomodulatory properties, yet these effects are incompletely understood in secondary systemic fungal infections following bacterial sepsis. We investigated a model of systemic inflammation to determine whether antimycotics (liposomal amphotericin B (L-AMB), itraconazol (ITC), and anidulafungin (ANI)) modulate the gene and protein expression as well as the phagocytic activity of lipopolysaccharide (LPS)-stimulated human monocytes.
THP-1 monocytes were incubated with L-AMB, ITC or ANI and LPS. Gene expression levels of cytokines (TNF-<alpha>, IL-1<beta>, IL-6, and IL-10) were measured after 2h, 6h, and 24h. Cytokine protein levels were evaluated after 24h and phagocytic activity was determined following co-incubation with Escherichia coli.
All antimycotics differentially modulated the gene and protein expression of cytokines in sepsis-like conditions. In the presence of LPS, we identified L-AMB as immunosuppressive, whereas ITC demonstrated pro-inflammatory properties. Both compounds induced remarkably less phagocytosis.
Our study suggests that antimycotics routinely used in septic patients alter the immune response in sepsis-like conditions by modulating cytokine gene and protein expression levels and phagocytic activity. Future treatment strategies should consider the immune status of the host and apply antimycotics accordingly in bacterial septic patients with secondary fungal infections.
Our study suggests that antimycotics routinely used in septic patients alter the immune response in sepsis-like conditions by modulating cytokine gene and protein expression levels and phagocytic activity. Future treatment strategies should consider the immune status of the host and apply antimycotics accordingly in bacterial septic patients with secondary fungal infections.
Meso-dihydroguaiaretic acid (MDA) is known for its anti-inflammatory, anti-oxidant, anti-bacterial, and anti-tumor activity. However, the anti-breast cancer effect and the mechanism of MDA remain undefined.
In this study, we examined the anti-cancer activity and the mechanisms of action of MDA in breast cancer cell lines, 4T-1 and MCF-7 cells; and 4T-1 bearing mouse model.
MDA showed cytotoxic effects on 4T-1 and MCF-7 cells in a dose-dependent manner. ML324 mw Moreover, MDA increased the amount of Annexin V-positive apoptotic bodies, phosphorylated JNK and p38 in 4T-1 cells. MDA also down-regulated cell-cycle dependent proteins, CDK-4 and cyclin D1; and induced cleaved caspase-3 in MDA-treated 4T-1 cells. We further verified that MDA-induced apoptosis is mediated by p38 and caspase-3 activation in 4T-1 cells. Next, we studied the effect of MDA treatment on cell migration and found that MDA significantly reduced cell migration. Moreover, MDA reduced EGFR and intergrin β3 expression, and dephosphorylated Src in a dose-dependent manner in 4T-1 cells. Furthermore, we observed in vivo effect of MDA in 4T-1 cell inoculated mice. MDA (20mg/kg/day) significantly suppressed mammary tumor volume and activated caspase-3 in tumor tissues.
These results suggest novel targets of MDA in breast cancer in vitro and in vivo, making it a potential candidate as a chemotherapeutic drug.
These results suggest novel targets of MDA in breast cancer in vitro and in vivo, making it a potential candidate as a chemotherapeutic drug.In this paper, an entropy-based method is proposed to forecast the demographical changes of countries. We formulate the estimation of future demographical profiles as a constrained optimization problem, anchored on the empirically validated assumption that the entropy of age distribution is increasing in time. The procedure of the proposed method involves three stages, namely 1) Prediction of the age distribution of a country's population based on an "age-structured population model"; 2) Estimation the age distribution of each individual household size with an entropy-based formulation based on an "individual household size model"; and 3) Estimation the number of each household size based on a "total household size model". The last stage is achieved by projecting the age distribution of the country's population (obtained in stage 1) onto the age distributions of individual household sizes (obtained in stage 2). The effectiveness of the proposed method is demonstrated by feeding real world data, and it is general and versatile enough to be extended to other time dependent demographic variables.The effects of pregabalin on neuropathic pain relief and the serum visfatin level were assessed using an experimental model of neuropathy in a study conducted on 40 male mice with sciatic nerve constriction. The mice were randomly assigned to 4 groups, each with 10 mice. The mice were subjected to experimental chronic partial constriction of the sciatic nerve and compared to sham-operated, saline-treated control mice (group I). The experimental groups (II-IV) were subjected to partial constriction of the left sciatic nerve. A series of behavioral tests, electrophysiological studies and biochemical measures were performed after 3 weeks of daily oral treatment with pregabalin (20 and 40 mg/kg in groups III and IV, respectively). The study revealed the actions of pregabalin against the nociceptive effects of chronic sciatic nerve constriction in mice (p less then 0.01), including replenishment of the glutathione level (p less then 0.05) and reduction of the serum visfatin level. No significant effect on the tissue malondialdehyde level was found for any of the pregabalin doses. The percentage differences in the maximum tetanic force between the ipsilateral and contra lateral legs were significant in both pregabalin-treated groups (p less then 0.05). We concluded that pregabalin reduced the serum visfatin level and produced a dose-dependent antinociceptive antioxidant effect.
The spinal cord is the main pathway for information, connecting the brain and the peripheral nervous system. Any disorder that results in spinal cord dysfunction will have a dramatic impact on the patient's quality of life. This review focusses on myelopathy, specifically, on the acute and subacute clinical presentations and the inflammatory and vascular etiology of this widespread disorder.
Myelopathy following spinal cord injury is a generic term referring to a lesion that affects the spinal cord following traumatic injury, or autoimmune, infectious, neoplastic, vascular and hereditary degenerative diseases. Depending on the patient's medical history, the underlying clinical syndrome and the temporal course of the manifestation, the clinician must account for a wide range of possible differential diagnoses.
Spinal cord disorders pose a tremendous challenge for the clinician, as they show great variability in clinical presentation but can have potentially devastating sequelae. The acute and sometimes urgent nature of therapeutic management is highly dependent on the underlying disorder, often necessitating a combination of approaches including surgical or conservative therapies (including immunomodulatory therapy) and an interdisciplinary approach to achieve the best outcomes.
Spinal cord disorders pose a tremendous challenge for the clinician, as they show great variability in clinical presentation but can have potentially devastating sequelae. The acute and sometimes urgent nature of therapeutic management is highly dependent on the underlying disorder, often necessitating a combination of approaches including surgical or conservative therapies (including immunomodulatory therapy) and an interdisciplinary approach to achieve the best outcomes.
Medication overuse headache (MOH) is the third most prevalent headache type after migraine and tension-type headache. A large number of studies on the long-term prognosis have shown that MOH has a high relapse rate after treatment. Although MOH relapse-related risk factors have been reported, no related research has been performed in China. Therefore, the purpose of this study was to analyze and evaluate the risk factors for MOH relapse in China.
Eighty-six out-patients of Shandong Provincial Hospital who were initially diagnosed with MOH, and who had successful withdrawal treatment within 2 months, were chosen from March 2012 to July 2013. All subjects were followed up by the investigators of this study. Of the 86 subjects, 27 who had relapsed were compared with 59 who had not relapsed (i.e. the controls). Based on a standardized questionnaire, a database was created (with Microsoft Excel 2010). The data, which included 38 indexes, were analyzed by univariate analysis with chi-square test, Fisher's exact test, t-test, or paired rank test. The statistically correlated (P<0.05) variables were chosen as the independent variables, thereby enabling the calculation of the non-conditional multivariate stepwise logistic regression.
The independent risk factors for medication-overuse headache relapse were determined as headache frequency before drug withdrawal, duration of primary headache, and headache frequency after drug withdrawal.
Headache frequency before drug withdrawal, duration of primary headache, and headache frequency after drug withdrawal may be the independent risk factors for MOH relapse in China.
Headache frequency before drug withdrawal, duration of primary headache, and headache frequency after drug withdrawal may be the independent risk factors for MOH relapse in China.
Patients with active rheumatoid arthritis (RA) despite anti-tumor necrosis factor(anti-TNF)agent treatment can switch to either a subsequent anti-TNF agent or a biologic with an alternative mechanism of action, such as rituximab; however, there are limited data available to help physicians decide between these 2 strategies. The objective of this analysis was to examine the effectiveness and safety of rituximab versus a subsequent anti-TNF agent in anti-TNF-experienced patients with RA using clinical practice data from the Corrona registry.
Rituximab-naive patients from the Corrona registry with prior exposure to ≥1 anti-TNF agent who initiated rituximab or anti-TNF agents (2/28/2006-10/31/2012) were included. Two cohorts were analyzed the trimmed population (excluding patients who fell outside the propensity score distribution overlap) and the stratified-matched population (stratified by 1 vs. ≥2 anti-TNF agents, then matched based on propensity score). The primary effectiveness outcome was achievement oexperienced patients with RA, rituximab was associated with an increased likelihood of achieving LDA/remission, mACR response and physical function improvement, with a comparable safety profile, versus subsequent anti-TNF agent users.
ClinicalTrials.gov NCT01402661 . Registered 25 July 2011.
ClinicalTrials.gov NCT01402661 . Registered 25 July 2011.Patients with non-metastatic esophageal cancer routinely undergo endoscopic ultrasound (EUS) for loco-regional staging. Neoadjuvant therapy is recommended for ≥T3 tumors while upfront surgery can be considered for ≤T2 lesions. The aim of this study was to determine if the degree of dysphagia can predict the EUS T-stage of esophageal cancer. One hundred eleven consecutive patients with non-metastatic esophageal cancer were retrospectively reviewed from a database. Prior to EUS, patients' dysphagia grade was recorded. Correlation between dysphagia grade and EUS T-stage, especially in reference to predicting ≥T3 stage, was determined. The correlation of dysphagia grade with EUS T-stage (Kendall's tau coefficient) was 0.49 (P less then 0.001) for the lower and 0.59 (P = 0.008) for the middle esophagus. The sensitivity and specificity of dysphagia grade ≥2 (can only swallow semi-solids/liquids) for T3 cancer were 56% (95% confidence interval [CI] 43-67%) and 93% (95% CI 79-98%), respectively. The sensitivity, specificity, and positive predictive value of dysphagia grade ≥3 (can only swallow liquids or total dysphagia) for T3 lesions were 36% (95% CI 25-48%), 100% (95% CI 89-100%), and 100% (95% CI 83-100%), respectively.
Website: https://www.selleckchem.com/products/ml324.html
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