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- R-flurbiprofen attenuates experimental autoimmune encephalomyelitis in mice. [JOURNAL ARTICLE]
- EMBO Mol Med 2014 Sep 30.
R-flurbiprofen is the non-cyclooxygenase inhibiting R-enantiomer of the non-steroidal anti-inflammatory drug flurbiprofen, which was assessed as a remedy for Alzheimer's disease. Because of its anti-inflammatory, endocannabinoid-modulating and antioxidative properties, combined with low toxicity, the present study assessed R-flurbiprofen in experimental autoimmune encephalomyelitis (EAE) models of multiple sclerosis in mice. Oral R-flurbiprofen prevented and attenuated primary progressive EAE in C57BL6/J mice and relapsing-remitting EAE in SJL mice, even if the treatment was initiated on or after the first flare of the disease. R-flurbiprofen reduced immune cell infiltration and microglia activation and inflammation in the spinal cord, brain and optic nerve and attenuated myelin destruction and EAE-evoked hyperalgesia. R-flurbiprofen treatment increased CD4(+)CD25(+)FoxP3(+) regulatory T cells, CTLA4(+) inhibitory T cells and interleukin-10, whereas the EAE-evoked upregulation of pro-inflammatory genes in the spinal cord was strongly reduced. The effects were associated with an increase of plasma and cortical endocannabinoids but decreased spinal prostaglandins, the latter likely due to R to S inversion. The promising results suggest potential efficacy of R-flurbiprofen in human MS, and its low toxicity may justify a clinical trial.
- Pre-treatment for ultrafiltration: effect of pre-chlorination on membrane fouling. [Journal Article]
- Sci Rep 2014.:6513.
Microbial effects are believed to be a major contributor to membrane fouling in drinking water treatment. Sodium hypochlorite (NaClO) is commonly applied in membrane cleaning, but its potential use as a pretreatment for controlling operational fouling has received little attention. In this study, the effect of adding a continuous low dose of NaClO (1 mg/l as active Cl) in combination with alum, before ultrafiltration, was compared with only alum as pretreatment. The results showed that the addition of NaClO substantially reduced membrane fouling both in terms of the rate of TMP development and the properties of the membrane cake layer. Although the size of nano-scale primary coagulant flocs changed little by the addition of NaClO, the cake layer on the membrane had a greater porosity and a substantially reduced thickness. NaClO was found to inactivate bacteria in the influent flow, which reduced both microbial proliferation and the production of proteins and polysaccharides in the cake layer and contributed significantly to improving the overall ultrafiltration performance. NaClO dosing had no adverse impact on the formation of currently regulated disinfection by-product compounds (THMs and HAAs).
- Tetramethylpyrazine Protects against Hydrogen Peroxide-Provoked Endothelial Dysfunction in Isolated Rat Aortic Rings: Implications for Antioxidant Therapy of Vascular Diseases. [Journal Article]
- Evid Based Complement Alternat Med 2014.:627181.
Objectives.Oxidative stress can initiate endothelial dysfunction and atherosclerosis. This study evaluated whether tetramethylpyrazine (TMP), the predominant active ingredient in Rhizoma Ligustici Wallichii (chuanxiong), prevents endothelial dysfunction in a rat model of oxidative stress. Methods. Isolated rat aortic rings were pretreated with various drugs before the induction of endothelial dysfunction by hydrogen peroxide (H2O2). Changes in isometric tension were then measured in acetylcholine- (ACh-) relaxed rings. Endothelial nitric oxide synthase (eNOS) expression was evaluated in the rings by Western blotting, and superoxide anion (O2 (∙-)) content was assessed in primary rat aortic endothelial cells by dihydroethidium- (DHE-) mediated fluorescence microscopy.
Results.ACh-induced endothelium-dependent relaxation (EDR) was disrupted by H2O2 in endothelium-intact aortic rings. H2O2-impaired relaxation was ameliorated by acute pretreatment with low concentrations of TMP, as well as by pretreatment with catalase and the NADPH oxidase inhibitors, apocynin and diphenyleneiodonium (DPI). TMP, apocynin, and DPI also reduced O2 (∙-) accumulation in endothelial cells,but TMP failed to alter eNOS expression in aortic rings incubated with H2O2.
Conclusions.TMP safeguards against oxidative stress-induced endothelial dysfunction, suggesting that the agent might find therapeutic utility in the management of vascular diseases. However, TMP's role in inhibiting NADPH oxidase and its vascular-protective mechanism of action requires further investigation.
- Effects of basic fibroblast growth factor dose on traumatic tympanic membrane perforation. [Journal Article]
- Growth Factors 2014 Oct; 32(5):150-4.
Abstract Objective: To compare the healing outcomes of higher and lower doses of basic fibroblast growth factor (bFGF) on human traumatic tympanic membrane perforation (TMP).Prospective clinical study.All patients with traumatic TMP were treated by direct application of bFGF, and were sequentially allocated into one of two groups: lower-dose group (2-3 drops of bFGF solution daily, approximately 0.1-0.15 mL) and higher-dose group (5-6 drops of bFGF solution daily, approximately 0.25-0.3 mL). The results of closure rate, closure time, and rate of otorrhea between the higher- and lower-dose groups were compared at 3 months.In total, 126 patients were included in this study. The higher-dose group showed significantly improved purulent otorrhea rate compared with the lower-dose group (p < 0.01) for perforations of the same size, although the closure rate of the middle-sized perforations did not differ significantly between higher- and lower-dose groups (p > 0.05). However, the lower-dose group had a significantly shorter closure time of 5 d compared with the higher-dose group (p < 0.05). In addition, although the lower-dose group showed shorter healing times (about 3 d) compared to the higher-dose group for large-sized perforations, the dosage of bFGF did not significantly affect the large-sized perforation closure rate (p > 0.05) or closure time (p > 0.05). Nine large-sized perforations with secondary purulent otorrhea achieved complete closure, with closure times of 7-25 (14.2 ± 5.8) d.This study suggested that continued daily application of a lower dose of bFGF not only shortens the closure time of human traumatic TMP but also avoids secondary purulent otorrhea.
- Post-Dilution Hemodiafiltration With a Heparin-Grafted Polyacrylonitril Membrane. [JOURNAL ARTICLE]
- Ther Apher Dial 2014 Sep 26.
The aim of this multicenter, prospective study was to explore the possibility of carrying out routine sessions of post-dilution hemodiafiltration with a polyacrylonitril membrane grafted with heparin (HeprAN) and reduced anticoagulation. Forty-four patients from eight centers were included in the study and treated by means of post-dilution on-line hemodiafiltration with automatic control of TMP, according to three different modalities tested consecutively: phase 1, polyethersulfone filter primed with heparinized saline and anticoagulated with continuous infusion of unfractionated heparin 1000/h; phase 2, HeprAN membrane filter primed with saline without heparin. Anticoagulation: a 1000-unit bolus of unfractionated heparin at the start of session followed by a second one at the end of the second dialysis hour; phase 3, same filter and priming procedure as in phase 2; anticoagulation with nadroparin calcium at the beginning of treatment. Partial or massive clotting of the dialyzer occurred in less than 1% of sessions in phase 1; 10% and 7% in phase 2; and 1% and 2% in phase 3. Clotting limited to the drip chambers was observed in 13%, 34% and 12%, respectively. The study of coagulation parameters showed a better profile when low-molecular weight heparin (LMWH) was used in association with HeprAN membrane, while the generation of TAT complexes did not differ from that observed with the standard anticoagulation modality used in phase 1. Our results suggest that the HeprAN membrane can be used safely in routine post-dilution hemodiafiltration with reduced doses of LMWH.
- Antisolvent precipitation of water-soluble hemicelluloses from TMP process water. [JOURNAL ARTICLE]
- Carbohydr Polym 2014 Nov 26.:411-419.
During the thermomechanical pulping (TMP) of spruce, hemicelluloses (mainly galactoglucomannans, GGMs) are released into the process water at relatively low concentrations that are currently impossible to efficiently recover. This paper examines the recovery of hemicelluloses precipitated from TMP process water via solubility reduction by adding antisolvents such as methanol, ethanol, and acetone. The phase separation was monitored by turbidity measurements. Gravimetric analysis, FTIR, GC-MS, UV spectroscopy, and ICP-OES were used to determine the yield, purity, and composition of the precipitates. Gel permeation chromatography and pulsed field-gradient self-diffusion NMR were used to measure the molecular mass distribution of the precipitates. Acetone was found to be the most efficient antisolvent, giving the highest yield at the lowest addition. The contents of lipophilic extractives and lignin impurities were below 0.5% and 1.6%, respectively, and the metal content was approximately 2% in the precipitates obtained with acetone.
- Long-term clinical outcome and phenotypic variability in hyperphosphatemic familial tumoral calcinosis and hyperphosphatemic hyperostosis syndrome caused by a novel GALNT3 mutation; case report and review of the literature. [JOURNAL ARTICLE]
- BMC Genet 2014 Sep 24; 15(1):98.
BackgroundHyperphosphatemic Familial Tumoral Calcinosis (HFTC) and Hyperphosphatemic Hyperostosis Syndrome (HHS) are associated with autosomal recessive mutations in three different genes, FGF23, GALNT3 and KL, leading to reduced levels of fibroblast growth factor 23 (FGF23) and subsequent clinical effects.ResultsWe describe a consanguineous family with two affected siblings with HFTC and HHS caused by a novel homozygous G-to T substitution in exon 3 of GALNT3 (c.767 G¿>¿T; p.Gly256Val), demonstrating great phenotypic variation and long asymptomatic intervals. Calcific tumors appeared at 14 years of age in the male, and the female displayed episodic diaphysitis from age 9 years. Symptoms of eye involvement were present in both from childhood, and progressed into band keratopathy in the female. Abnormal dental roots and tooth loss, as well as myalgia were present in both from their mid-twenties, while the female also had calcifications in the placenta, the iliac vessels and thyroid cartilage. New calcific tumors appeared more than 20 years after the initial episodes, delaying diagnosis and treatment until the ages of 37 and 50 years, respectively. Both siblings had elevated serum phosphate levels, inappropriately elevated tubular maximum phosphate reabsorption per unit glomerular filtration rate (TmP/GFR), reduced levels of intact FGF23 and increased levels of c-terminal FGF23. Review of all 54 previously published cases of GALNT3, FGF23, and KL associated HFTC and HHS demonstrated that more subjects than previously recognized have a combined phenotype.ConclusionWe have described HFTC and HHS in a consanguineous Caucasian family with a novel GALNT3 mutation, demonstrating new phenotypic features and significant variability in the natural course of the disease. A review of the literature, show that more subjects than previously recognized have a combined phenotype of HFTC and HHS. HHS and HFTC are two distinct phenotypes in a spectrum of GALNT3 mutation related calcification disorders, where the additional factors determining the phenotypic expression, are yet to be clarified.
- Why not performing susceptibility test for trimethoprim-sulphamethoxazole? [JOURNAL ARTICLE]
- J Chemother 2014 Sep 23.:1973947814Y0000000215.
- Trimethoprim-sulfamethoxazole-induced aseptic meningitis-not just another sulfa allergy. [REVIEW]
- Ann Allergy Asthma Immunol 2014 Sep 17.
To review the literature on trimethoprim-sulfamethoxazole (TMP-SMX)-induced aseptic meningitis (TSIAM) and discuss the features, possible mechanisms, evaluation, and treatment options relevant for the allergist.A MEDLINE search was performed using the terms aseptic meningitis, trimethoprim-sulfamethoxazole, trimethoprim, and sulfamethoxazole.Cases were included that fit the case definition of headache, neck pain, or change in mental status with elevated cerebrospinal fluid white blood cell count or protein attributable to TMP-SMX or either medication alone.Forty-one patient cases were reviewed. There was a predominance of female patients and patients with autoimmune disease reported. Fever, headache, neck pain, and altered mental status were the most common findings reported in TSIAM reactions. Severe reactions ranged from hypotension to seizure and unconsciousness or coma. Typical cerebrospinal fluid findings included elevated white blood cell count with neutrophil predominance, elevated protein, and normal glucose. Symptoms quickly remitted with withdrawal of TMP-SMX, typically over 48 to 72 hours. Full recovery was typically experienced, although permanent paraplegia was reported in 1 case. The mechanism of reaction is unknown, although an IgE-mediated reaction is unlikely. Many patients experienced multiple TSIAM reactions before the diagnosis was made. Diagnosis can be confirmed with drug challenge or graded test dosing when necessary. Patients with TSIAM subsequently reacted to TMP and SMX alone and therefore should be advised to avoid these 2 classes of medication after diagnosis.TMP-SMX is the most common antibiotic to cause drug-induced aseptic meningitis. By being aware of this reaction, allergists are well poised to diagnose TSIAM and prevent future reoccurrences for the patient.
- Tetramethylpyrazine Suppresses Transient Oxygen-Glucose Deprivation-Induced Connexin32 Expression and Cell Apoptosis via the ERK1/2 and p38 MAPK Pathway in Cultured Hippocampal Neurons. [Journal Article]
- PLoS One 2014; 9(9):e105944.
Tetramethylpyrazine (TMP) has been widely used in China as a drug for the treatment of various diseases. Recent studies have suggested that TMP has a protective effect on ischemic neuronal damage. However, the exact mechanism is still unclear. This study aims to investigate the mechanism of TMP mediated ischemic hippocampal neurons injury induced by oxygen-glucose deprivation (OGD). The effect of TMP on hippocampal neurons viability was detected by MTT assay, LDH release assay and apoptosis rate was measured by flow cytometry. TMP significantly suppressed neuron apoptosis in a concentration-dependent manner. TMP could significantly reduce the elevated levels of connexin32 (Cx32) induced by OGD. Knockdown of Cx32 by siRNA attenuated OGD injury. Moreover, our study showed that viability was increased in siRNA-Cx32-treated-neurons, and neuron apoptosis was suppressed by activating Bcl-2 expression and inhibiting Bax expression. Over expression of Cx32 could decrease neurons viability and increase LDH release. Furthermore, OGD increased phosphorylation of ERK1/2 and p38, whose inhibitors relieved the neuron injury and Cx32 up-regulation. Taken together, TMP can reverse the OGD-induced Cx32 expression and cell apoptosis via the ERK1/2 and p38 MAPK pathways.