Clinical Effect of Tiaoxin Formula in Treatment of Patients with Coronary Heart Disease and Anxiety/Depression and Its Impact on Serum 5-HT， β-TG and MPO Levels / 中国实验方剂学杂志

ObjectiveTo explore the clinical effect of Tiaoxin formula in the treatment of patients with coronary heart disease and anxiety/depression and its impact on serum levels of 5-hydroxytryptamine （5-HT）， β- thromboglobulin （β-TG） and myeloperoxidase （MPO）. MethodA total of 66 patients with coronary heart disease and anxiety/depression were randomly divided into the Tiaoxin formula group and Deanxit group， 33 cases in each group. Both groups were given fundamental western treatment for coronary heart disease. Additionally， the Deanxit group was treated with flupentixol and melitracen tablets and the Tiaoxin formula group was treated with Tiaoxin Formula. The treatment lasted 8 weeks. Before and after treatment， the changes of clinical efficacy， Patient Health Questionnaire （PHQ-9）， Generalized Anxiety Disorder （GAD-7） scale， Seattle Angina Questionnaire （SAQ）， heart rate variability， and serum 5-HT， β-TG and MPO levels， and incidence of adverse reactions in the two groups were observed. ResultThere was no significant difference in the baseline indexes of patients in the two groups， and thus the two groups were comparable. After treatment for 8 weeks， the total effective rate for traditional Chinese medicine （TCM） syndromes in the Tiaoxin Formula group was 87.88% （29/33） higher than 63.64% （21/33） in the Deanxit group （Z=-2.653， P<0.05）. Compared with those before treatment， the PHQ-9 and GAD-7 scores of the two groups were decreased at week 4 and 8 of treatment （P<0.05）， and there was no statistical difference between two groups. And the SAQ dimension scores of the two groups were increased at week 4 and 8 of treatment （P<0.05）. Compared with the Deanxit group， the Tiaoxin Formula group had elevation in two dimension scores： Physical limitation and angina stability （P<0.05）. Compared with the conditions before treatment， the serum 5-HT level in the two groups were increased， while the β-TG and MPO levels were lowered （P<0.05）， and there was no distinct difference between two groups. In addition， the standard deviation of normal-to-normal intervals （SDNN） and standard deviation of average normal-to-normal intervals （SDANN） of the heart rate variability in the Tiaoxin formula group were elevated after treatment （P<0.05）， which were more significant than those of the Deanxit group （P<0.05）. During the treatment period， the incidence of adverse drug reactions in the Tiaoxin formula group was lower than that in the Deanxit group （P<0.05）， and no adverse events were observed in the two groups. ConclusionTiaoxin formula was effective for the treatment of patients with coronary heart disease accompanied by anxiety and depression， which improved the clinical symptoms， increased serum 5-HT levels， and decreased serum β-TG and MPO levels， and had few adverse reactions and high safety for patients， showing a high clinical value.

The role of neutrophil extracellular trap in the diagnosis and treatment of complications after liver transplantation / 器官移植

Prevention and treatment of complications after liver transplantation play a significant role in maintaining liver graft function and improving clinical prognosis of the recipients. Neutrophil extracellular trap (NET) are fibrous net-like structures composed of DNA as the skeleton and histones and granular proteins released by activated neutrophils. Studies have shown that the activation of neutrophils and the release of NET in donor liver after liver transplantation are involved in the incidence of multiple liver transplantation-related complications including ischemia-reperfusion injury, acute rejection, acute liver failure and recurrence of hepatocellular carcinoma, etc. In this article, the effect of NET on the complications after liver transplantation was mainly assessed, and research progress on NET as a potential target for the prevention and treatment of complications after liver transplantation was reviewed, aiming to provide reference for the prevention and treatment of complications after liver transplantation, enhance clinical efficacy of liver transplantation and improve clinical prognosis of the recipients.

Improvement of indirect immunofluorescence technique to detect antineutrophil cytoplasmic antibodies and its impact on test positivity rate

The indirect immunofluorescence (IIF) technique for antineutrophil cytoplasmic antibodies (ANCA) detection is subject to substantial differences across laboratories. This study aimed to assess the impact of improvements in the IIF-ANCA technique on the positivity rate of ANCA tests. A cross-sectional study was performed with serum samples from patients with ANCA-associated vasculitis (AAV), autoimmune hepatitis (AIH), and ulcerative colitis (UC). A paired analysis was performed for IIF-ANCA results using the traditional method and a modified protocol after a series of specific adjustments in the technique based on the protocol of IIF-ANCA test performed at a nation-wide private laboratory in Brazil. ANCA specificity was assessed by ELISA for anti-proteinase 3 (PR3) and anti-myeloperoxidase (MPO) antibodies. Sixty-one patients were evaluated. The positivity rate of IIF-ANCA tests at disease presentation performed at the University reference laboratory was 32.3% in AAV, AIH, and UC patients, whereas the positivity rates of IIF-ANCA and ELISA tests in other laboratories were 75.0 and 72.7%, respectively. After modifications in the IIF-ANCA technique, there was a significant increase in the positivity rate (14.8 vs 34.3%; P=0.0002) and in median titers [1/40 (1/30-1/160) vs 1/80 (1/40-1/80); P=0.0003] in AAV, AIH, and UC patients. UC had the highest increment in positive results from 5.3 to 36.8%. There was poor agreement between MPO- or PR3-ANCA and both IIF-ANCA techniques. In conclusion, modifications in the IIF-ANCA protocol led to a significant improvement in its positivity rate and titers.

Anti-Myeloperoxidase (MPO) associated Vasculitis in a young Filipino Male with Bronchiectasis: A case report

Background@#ANCA-associated vasculitis and its subtypes have been associated with pulmonary manifestations, with bronchiectasis being a unique clinical presentation.@*Case Summary@# We report the case of a 26-year-old Filipino male who presented with progressive dyspnea, neuropathic pain, and purpuric rash. Diagnostic evaluation revealed upper lobe bronchiectasis and lower lobe pneumonia, as well as hematuria and proteinuria. ANCA-associated vasculitis (AAV) and tuberculosis were considered. There was improvement of dyspnea, cough and rashes with antibiotics, glucocorticoids (GC), and anti-TB coverage. However, neuropathic pain progressed to the upper and lower extremities with development of weakness. Anti-myeloperoxidase (MPO) Anti-Neutrophil Cytoplasmic Antibody (ANCA) was positive, Electromyography-Nerve Conduction Velocity (EMG-NCV) revealed diffuse sensorimotor axonal polyradiculopathy of both upper and lower extremities. Cyclophosphamide was then given. The patient gradually regained his motor strength while sensory deficits persisted. He was referred to rehabilitation medicine for physical therapy and eventually discharged. This case highlights vasculitis as an associated extrapulmonary manifestation of bronchiectasis, and the possible role of bronchiectasis in the immune-mediated pathogenesis of ANCA- associated vasculitides.

Effect of non-nucleoside reverse transcriptase inhibitors and protease inhibitors on serum levels of myeloperoxidase and C-reactive protein in HIV-infected individuals

Abstract It remains unclear whether increased inflammatory and cardiovascular risk biomarkers differ depending on the class of antiretroviral that is used. This study evaluated the plasma levels of inflammatory and cardiovascular risk biomarkers, such as MPO, hs-CRP, glucose, lipid profile, ALT (GPT), AST (GOT), urea and creatinine, as well as the blood count, of all the 164 participants in the study, either infected or un-infected with HIV. Thirty of the 104 HIV-infected individuals did not receive any antiretroviral; twenty-four of them were treated with non-nucleoside reverse transcriptase inhibitor class; and fifty took protease inhibitors. The control group consisted of sixty non-HIV infected individuals. In the case of the HIV-infected volunteers, the CD4+ T lymphocyte counts and viral load were also analyzed. Regardless of the hematological and biochemical changes resulting from the antiretroviral therapy (ART), the MPO and hs-CRP values significantly increased for the HIV-infected individuals (treated or untreated), irrespective of the class of ART that was used. This is important because these biomarkers are designed to be predictors of the risk of cardiovascular disease. The results of this study provide supporting evidence for the hypothesis that HIV-infected individuals are at increased risk of developing cardiovascular disease related to chronic inflammations, despite virological control with ART, and regardless of the class of ART that is used.

Suppression of L-arginine-induced acute necrotizing pancreatitis in rats by metformin associated with the inhibition of myeloperoxidase and activation of interleukin-10 / Supresión de la pancreatitis necrotizante aguda inducida por L-arginina en ratas por metformina asociada con la inhibición de mieloperoxidasa y activación de interleucina-10

SUMMARY: Acute pancreatitis is a frequent life-threatening inflammatory disease of the pancreas characterized by severe abdominal pain that lasts for days to weeks. We sought to determine whether the antidiabetic and anti-inflammatory drug, metformin can substantially protect against acute pancreatitis in an animal model of L-arginine-induced acute pancreatitis, and whether this is associated with the augmentation of the anti-inflammatory cytokine interleukin-10 (IL-10) and inhibition of the enzyme that promotes tissue damage, myeloperoxidase (MPO). Rats were either injected with two doses of the amino acid L-arginine (2.5 gm/kg; i.p., at one-hour intervals) before being sacrificed after 48 hours (model group) or were pretreated with metformin (50 mg/kg) daily for two weeks prior to L- arginine injections and continued receiving metformin until the end of the experiment (protective group). Using microscopic examination of the pancreas and blood chemistry, we observed that L-arginine induced acute pancreatic injury. This is demonstrated by an enlarged pancreas with patchy areas of haemorrhage, vacuolated cytoplasm and pyknotic nuclei in the acini, disorganized lobular architecture with infiltration of inflammatory cells within the interlobular connective tissue (CT) septa, and the presence of congested blood vessels that were substantially ameliorated by metformin. Metformin also significantly (p<0.05) inhibited L-arginine-induced MPO, lactate dehydrogenase (LDH), and the inflammatory biomarker tumor necrosis factor alpha (TNF-α). Whereas, metformin significantly (p<0.05) increased IL-10 levels that were inhibited by pancreatitis induction. We further demonstrated a significant (p<0.001) correlation between the scoring of the degree of pancreatic lobules damage tissue damage and the blood levels of TNF-α, IL-10, LDH, and MPO. Thus, metformin effectively protects against L-arginine-induced acute pancreatitis, which is associated with the inhibition of MPO and augmentation of IL-10.

RESUMEN: La pancreatitis aguda es una enfermedad inflamatoria del páncreas que amenaza la vida y se caracteriza por un dolor abdominal intenso que dura de días a semanas. Buscamos determinar si la metformina, fármaco antidiabético y antiinflamatorio, puede proteger contra la pancreatitis aguda en un modelo animal de pancreatitis aguda inducida por L-arginina. Además se estudió la asociación con el aumento de la citocina antiinflamatoria interleucina-10. (IL-10) e inhibición de la enzima que promueve el daño tisular, mieloperoxidasa (MPO). Las ratas se inyectaron con dos dosis del aminoácido L-arginina (2,5 g / kg; ip, a intervalos de una hora) antes de ser sacrificadas des- pués de 48 horas (grupo modelo) o se pre trataron con metformina (50 mg / kg) durante dos semanas antes del tratamiento de L- arginina y continuaron recibiendo metformina hasta el final del experimento (grupo protector). Mediante el examen microscópico del páncreas y la química sanguínea, se observó que la L- arginina inducía una lesión pancreática aguda. Se observó un aumento significativo de tamaño del páncreas con áreas hemorrágicas, citoplasma vacuolado y núcleos picnóticos en los acinos, arquitectura desorganizada con infiltración de células inflamatorias dentro de los tabiques del tejido conjuntivo interlobulillar (TC) y la presencia de vasos sanguíneos congestionados mejorados por metformina. Se observó que la metformina inhibió significativamente (p <0,05) la MPO inducida por L- arginina, la lactato deshidrogenasa (LDH) y el factor de necrosis tumoral alfa (TNF-α). Además, demostramos una correlación significativa (p <0,001) entre la puntuación del grado de daño tisular de los lóbulos pancreáticos y los niveles sanguíneos de TNF-α, IL-10, LDH y MPO. Por tanto, la metformina protege eficazmente contra la pancreatitis aguda inducida por L-arginina, que se asocia con la inhibición de MPO y el aumento de IL-10.

W3D improves LPS-induced acute lung injury in mice by regulating TLR4/MD2-NF-κB p65 signaling pathway / 中国药理学通报

Aim To investigate the protective effect of new structure compound 4-(5'-dimethylamino)-naphthalenesulfonyl-2 (3H)-benzoxazolone (W3D) on lipopolysaccharide (LPS) induced acute lung injury (ALI) and the underlying mechanism. Methods ICR mice were randomly divided into control group, LPS model group, chlorzoxazone (12.5 mg · kg

Study on ulcerative colitis activity and its chemical constituents in effective part of Gardeniae Fructus / 中国药理学通报

Aim To study the therapeutic effect of 35% and 70% ethanol elution sites of Gardeniae Fructus extract on 2,4,6-trinitrobenzene sulfonic acid (TNBS)/ethanol induced ulcerative colitis (UC) in rats, and to identify the chemical composition of the active elution site using mass spectrometry. Methods The UC model induced by TNBS was used in rats, and the different eluted parts were administered by gavage at a dose of 2. lg/kg for 7 days. Body weight measurement , disease activity index (DAI) score, and pathological score of colon tissues were compared. Myeloperoxidase (MPO) , superoxide dismutase (SOD), malondialdehyde ( MDA ) , nitric oxide ( NO ) , tumor necrosis factor-a (TNF-a) , interleukin in mouse colon tissue -6 (IL-6), interleukin-1 (3 (IL-ip) levels were compared among groups. Liquid-mass spectrometry was used to identify the chemical components of the parts with better efficacy. Results Compared with model group, the weight loss in 35% elution site group was significantly improved, the DAI and histopathology scores were markedly reduced, and the contents of MPO, NO, MDA, TNF-a, IL-6 and IL-1(3 in tissues were apparently reduced. SOD content increased significantly (P <0. 01). A total of 19 chemical components were identified by LC-MS, 11 of which were iri- doids. Conclusions The 35% elution site of Gardeni- a has obvious therapeutic effect on UC rats, and the iridoid component may be the material basis for its function.

Assessment of Cardiovascular Disease Risk in Prediabetes

This study was aimed at investigating the nutrient and bioactive components of Annona muricataand Fagara zanthxoyloidefrom south-southern Nigeria. The roots and leaves of these plants were collected from communities within this region and an analysis of the phytochemical, mineral and vitamin components of these plant parts were carried out using standard methods. The results of the investigation revealed the a high presence of alkaloids (27.34 ± 0.15 and 12.98 ± 0.98), flavonoids (19.66 ± 0.04 and 3.71 ± 0.46) and phenols (15.10 ± 0.11 and 0.07 ± 0.42) in the leaves and roots of Annona muricatawhile alkaloids (35.55 ± 0.95 and 50.90 ± 0.83), tannins (28.70 ± 0.19 and 55.37 ± 0.47) and terpenoids (18.23 ± 0.08 and 41.21 ± 0.16) were observed in leaves and roots of Fagara zanthoxyloide. Mineral analysis revealed the presence of iron (20.23 ± 0.01 and 5.21 ± 0.02), calcium (3.67 ± 0.06 and 1.59 ± 0.01), copper (2.17 ± 0.011 and 0.16 ± 0.01) and magnesium (3.04 ± 0.01 and 2.18 ± 0.005) in leaves and roots of Annona muricataand iron, copper (2.53 ± 0.011and 7.38 ± 0.017) and zinc (5.16 ± 0.02 and 5.32 ± 0.011) in leaves and roots of Fagara zanthoxyloide.The leaves and roots of both plants also showed the presence of folate (26.82±0.48 and 23.47±0.03 for A. muricata and 15.82±0.18 and 20.63±0.91 for F. zanthoxyloide) and ascorbate (31.97±0.03and 26.89±0.19 for A. muricataand13.86±0.13 and 30.21±0.01for F. zanthoxyloide) in appreciable quantities while vitamins D, E and K were also observed in minute concentrations in both plant samples. These results may thus suggest that these plants from this region as a result of their rich nutrients and bioactive compositions may play a large role in alleviating the salient nutritional, physiological and medical challenges observed among people within this region.

Trimetazidine reduces formation of neutrophil extracellular traps via inhibiting autophagy / 中国药理学通报

Aim To study the effects of trimetazidine (TMZ)on theformationof neutrophil extracellular traps (NETs) induced by oxidized low-density lipoprotein (ox-LDL) in vitro and its relationship associated with cell autophagy. Methods The bone marrow neutrophils of mice were extracted by density gradient centrifugation,and NETs induction model was established using ox-LDL. Furthermore, TMZ, autophagy inhibitor LY294002 and autophagy inducer Rapamycin were added to disturb the induction of NETs induced by ox-LDL. The production of NETs marker MPO-DNA and the content of cfDNA/nets in the supernatantwere observed. Meanwhile, Western blot was employed to determine the protein expression of myeloperoxidase (MPO),beclin-l and LC3b in neutrophils. Results Treatment of ox-LDL to adhered neutrophils could lead to the formation of extracellular MPO-DNA and cfDNA/nets generation in a time-and concentration-dependent manner. The protein expression of LC3b,beclin-1 and MPO in neutrophils was up-regulated after treatedwith ox-LDL. TMZ pretreatment significantly inhibited NETs release and reduced the protein expression of LC3b,beclin-1 and MPO in neutrophils,which could be simulated by PI3K/AKT pathway blocker LY294002, while AKT/mTOR inhibitor rapamycin preconditioning did the opposite. Conclusions Ox-LDL-induces the formation of NETs in a time-and concentration-dependent manner. TMZ could down-regulate the level of autophagy and neutrophils, inhibit the induction of ox-LDL on NETs and reduce the release of NETs.

Multi-factorial risk stratification in Acute Coronary Syndrome

Background: ST elevated myocardial infarction (STEMI), non-ST elevated myocardial infarction (NSTEMI) and unstable anginas (UA) are continual spectrum of coronary artery disease (CAD).These are terminal events arising as a result of coronary artery atherosclerosis and superimposed thrombosis.Materials and methods: A prospective study in which a total of 91 patients of either sex aged 20 to 60 years were recruited, of which 30 were STEMI, 31 were NSTEMI/ unstable angina and 30 were age and sex matched healthy controls. Patients with following complaints of maximum 24 hours duration were registered in the emergency department and were included in the study (ACC/AHA Guidelines, 2002).Results: In the present study, 91 subjects were recruited from medical emergency department. All of the subjects were meeting the inclusion criteria. Of the total 91 subjects 30 were of STEMI (Group 1),15 were of NSTEMI (Group 2), 16 were of unstable angina (Group 3) and 30 were controls (Group4).Conclusion: In patients of ACS, MPO is raised as compared to controls. Also in complicated ACS,irrespective of other risk factors, MPO was significantly raised as compared to controls and can beused to predict immediate clinical complication. There is no significant association between MPO, hs Chowdhury P, Pandey V, Avasthi R, Kandukuri MK, Giri S, Sharma S. Multi-factorial risk stratification in Acute Coronary Syndrome. IAIM, 2016; 3(1): 36-45.Page 37 CRP and CK-MB when taken together to predict complications. TIMI risk score is a simple prognostication scheme that categorizes a patient's risk of death and ischemic events and provides a basis for therapy.

Association between MPO gene polymorphism and clinical characteristics in children with Kawasaki disease / 临床儿科杂志

Objective To investigate the association between MPO gene single nucleotide polymorphisms (SNP) loci (rs2333227,-643G/A) and clinical characteristics in Kawasaki disease (KD) in Han population in central China. Methods A case-control study was performed. Two hundred and thirty-seven children with KD and 249 normal children were recruited. The polymorphism distribution of SNP was detected using PCR-RFLP. The clinical data of children with KD were collected. Results The frequency of SNP loci (rs2333227) genotypes (GG, GA, AA) was signiifcantly different between children with KD and normal children (P=0.039), the allele frequency was also signiifcantly different between two groups (P=0.012), and the G allele was the risk factor. Compared with other genotypes, KD children with GG genotype had higher frequency in hand-foot edema (P=0.029). The SNP polymorphism was also associated with peritoneal effusion (P=0.028), however this SNP polymorphism was not associated with conjunctival hyperemia, oral mucosa lesions, and coronary artery lesion (P>0.05), also was not associated to imaging characteristics of hepatomegaly, splenomegaly, and lobular pneumonia (P>0.05). Conclusion The SNP loci (rs2333227) in MPO gene was associated with KD susceptibility, the G allele was a risk factor, and the SNP polymorphisms is associated with some clinical characteristic.

Comparison of chemiluminescent microparticle immunoassay and enzyme-linked immunosorbent assay for determination of anti-neutrophil cytoplasm antibodies / 中国免疫学杂志

Objective:To compare the performance of chemiluminescent microparticle immunoassay ( CMIA) and enzyme-linked immunosorbent assay ( ELISA) for the determination of Anti-PR3 and Anti-MPO.Methods:Concentration of Anti-PR3 and Anti-MPO in serum samples from 166 patients with autoimmune diseases and 50 healthy donors were determined by using CMIA (Method A) and ELISA(Method B),respectively.The results from both assays were analyzed and compared by statistical methods .Results:Method A showed better intra-assay reproducibility and inter-assay reproducibility than Method B for the determination of high ,medium and low levels of control serum .Both methods met the accuracy requirement .The correlation coefficient of Anti-PR3 and Anti-MPO were 0.987 8 and 0.989 6 for Method A and Method B ,respectively.And the Kappa coefficients were 0.897 and 0.882 for Method A and Method B,respectively.Conclusion:The performance of Method A is superior to Method B for the deter-mination of Anti-PR3 and Anti-MPO, which makes Method A to be a potentially better choice for clinical application .

Effects of Xianfu Wenyang Tongluo Drink on ANCA Associated Antigen in Thromboangiitis Obliterans Rat Models / 中国中医药信息杂志

Objective To observe the effects of Xianfu Wenyang Tongluo Drink (XFWYTLD) on ANCA associated antigen in rats with thromboangiitis obliterans;To discuss its mechanism. Methods Totally 72 SPF male Wistar rats were randomized into sham-operation group, model group, Mailuoning Granule group and XFWYTLD low, medium, and high dose groups. Method of femoral artery injecting sodium laurate was used to duplicate models. From the second day after modeling, the rats in sham-operation group and model group were fed with distilled water, while other groups received gavage with relevant medicine. 15 days later, the activity of MPO in serum was detected through the method of ultraviolet spectrophotometry;the protein expressions of PR3 and LAMP-2 in femoral artery and the surrounding tissues were detected through the method of immunohistochemisty. Results Compared with sham-operation group, the activity of MPO in serum and the protein expressions of PR3 and LAMP-2 in rats of model group were significantly higher;Compared with model group, the activity of MPO in serum and the protein expressions of PR3 and LAMP-2 in rats of all medication administration groups decreased, among which the XFWYTLD medium dose group showed the most obvious decrease. Conclusion XFWYTLD may lower levels of ANCA associated antigen, and further inhibit humoral immune function.

Effects of P38MAPK on erythropoietin postconditioning attenuating pneumocyte apoptosis after lung ischemia/reperfusion injury / 中国药学杂志

OBJECTIVE: To investigate the effects of P38MAPK on erythropoietin (EPO) postconditioning attenuating pneumocyte apoptosis after lung ischemia/reperfusion injury (LIRI) in rats. METHODS: Adult male Sprague-Dawley rats were randomly divided into 5 groups based upon the intervention (n=8); control group (C), LIRI group (I/R), LIRI+EPO group (EPO), EPO+solution countrl group (D), EPO+SB203580 group (SB). At the end of the experiment, blood specimens drawn from the arteria carotis were tested for the content of malondialdehyde (MDA), the activity of superoxide dismutase (SOD) and myeloperoxidase (MPO). The histological structure of the left lung was observed under light microscope, and scored by alveolar damage index of quantitative assessment (IQA). The pneumocyte apoptosis index (AI) was achieved by terminal deoxynucleotidyl transferase mediated dUTP nick end a-beling (TUNEL). RESULTS: Compared with C group, in I/R group IQA, AI and MDA level, MPO activity were significantly increased, SOD activity was reduced (P<0.05 or P<0.01), and morphological abnormality occurred in lung tissue. Compared with 1/R group, IQA, AI and MDA level, MPO activity were significantly decreased, SOD activity was improved (P<0.05 or P<0.01), and morphological abnormality in lung tissue was obviously reduced in EPO, D and SB groups. There were no significant difference in all of the indexes between D and EPO groups (P≤0.05). However, compared with EPO group, SOD activity was increased (P<0.05 or P<0.01), the other indexes were obviously reduced, and the abnormal changes of the morphology in I/R were also improved markedly in SB group. CONCLUSION: EPO may attenuate pneumocyte apoptosis in LIRI by reducing oxidant generation, neutrophils filtration, then inhibiting activation of P38MAPK.

Effects and mechanisms of vitexin against ulcerative colitis in mice / 中国药理学通报

Aim To evaluate the effect and mecha-nism of vitexin in a mouse model of DSS-induced ulcer-ative colitis (UC).Methods C57BL/6 mice were randomly placed into three groups: normal control group,DSS group and DSS +Vitexin group.Mice coli-tis was induced by adding 4% dextran sulphate sodium (DSS)into the drinking water for seven days.Vitexin was administered once a day along with DSS treatment. Mice were monitored daily with body weight change and diarrhea symptoms.After sacrifice,colon was re-moved and fixed in 1 0% (W/V)buffered formalin for hematoxylin-eosin (H&E)staining.Histological dam-age was assessed as a combined score of inflammatory cell infiltration and mucosal damage.The remaining colon pieces were collected to measure the activity of myeloperoxidase (MPO)by ELISA method and to de-termine the mRNA expression of TNF-α,IL-6 and COX-2.Results None of the mice receiving vehicle alone exhibited body weight loss and mucosal disrup-tion at any point during the study.Vitexin treatment significantly ameliorated DSS-induced body weight loss and histological score.The activity of MPO and the mRNA expression of TNF-α,IL-6 and COX-2 were markedly inhibited by vitexin treatment.Conclusion Vitexin ameliorates DSS-induced colitis through sup-pressing leukocyte infiltration and pro-inflammatory mediators production.

Chronically Elevated Myeloperoxidase Antineutrophil Cytoplasmic Antibody Levels in an Asymptomatic 91-year-old Patient / General Medicine

Myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) associated glomerulonephritis is commonly diagnosed in elderly patients with acute kidney injury (AKI). Prompt diagnosis and rapid initiation of appropriate therapy are essential to avoid the development of ANCA-associated vasculitis, which can be a life- and organ-threatening disease. We report a rare case of a 91-year-old male with a high MPO-ANCA titer, who took allopurinol, and showed no symptoms for >20 months, following which sudden AKI and severe bronchial asthma necessitated hemodialysis and steroid administration. Chronically elevated ANCA titers should be examined for causes and followed up to limit the risk of subsequent disease development.

In vivo and in vitro anti-inflammatory activity of Cryptostegia grandiflora Roxb. ex R. Br. leaves

BACKGROUND: Despite Cryptostegia grandiflora Roxb. ex R. Br. (Apocynaceae) leaves are widely used in folk Caribbean Colombian medicine for their anti-inflammatory effects, there are no studies that support this traditional use. Therefore, this work aimed to evaluate the effect of the total extract and primary fractions obtained from Cryptostegia grandiflora leaves, using in vivo and in vitromodels of inflammation, and further get new insights on the mechanisms involved in this activity. RESULTS: Ethanolic extract of Cryptostegia grandiflora leaves, and its corresponding ether and dichloromethane fractions, significantly reduced inflammation and myeloperoxidase activity (MPO) in ear tissue of mice treated with 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Histological analysis revealed a reduction of edema and leukocyte infiltration. Complementarily, we demonstrated that extract and fractions reduced nitric oxide (NO•) and prostaglandin E2 (PGE2) production in LPS-stimulated RAW 264.7 macrophages, as well as scavenging activity on DPPH and ABTS radicals. CONCLUSIONS: Our results demonstrated for the first time the anti-inflammatory activity of Cryptostegia grandiflora leaves, supporting its traditional use. This activity was related to inhibition of MPO activity, and PGE2 and NO• production. These mechanisms and its antioxidant activity could contribute, at least in part, to the anti-inflammatory effect showed by this plant.

Battling malaria iceberg incorporating strategic reforms in achieving Millennium Development Goals & malaria elimination in India.

Malaria control in India has occupied high priority in health sector consuming major resources of the Central and State governments. Several new initiatives were launched from time to time supported by foreign aids but malaria situation has remained static and worsened in years of good rainfall. At times malaria relented temporarily but returned with vengeance at the local, regional and national level, becoming more resilient by acquiring resistance in the vectors and the parasites. National developments to improve the economy, without health impact assessment, have had adverse consequences by providing enormous breeding grounds for the vectors that have become refractory to interventions. As a result, malaria prospers and its control is in dilemma, as finding additional resources is becoming difficult with the ongoing financial crisis. Endemic countries must contribute to make up the needed resources, if malaria is to be contained. Malaria control requires long term planning, one that will reduce receptivity and vulnerability, and uninterrupted financial support for sustained interventions. While this seems to be a far cry, the environment is becoming more receptive for vectors, and epidemics visit the country diverting major resources in their containment, e.g. malaria, dengue and dengue haemorrhagic fevers, and Chikungunya virus infection. In the last six decades malaria has taken deep roots and diversified into various ecotypes, the control of these ecotypes requires local knowledge about the vectors and the parasites. In this review we outline the historical account of malaria and methods of control that have lifted the national economy in many countries. While battles against malaria should continue at the local level, there is a need for large scale environmental improvement. Global Fund for AIDS, Tuberculosis and Malaria has provided huge funds for malaria control worldwide touching US$ 2 billion in 2011. Unfortunately it is likely to decline to US$ 1.5 billion in the coming years against the annual requirement of US$ 5 billion. While appreciating the foreign assistance, we wish to highlight the fact that unless we have internal strength of resources and manpower, sustained battles against malaria may face serious problems in achieving the final goal of malaria elimination.

Polimorfismo dos genes NQO1 e PON1 na etiologia das leucemias agudas infantis

As leucemias pediátricas são doenças hetereogêneas, consequentes da combinação de susceptibilidade genética individual e exposições a fatores ambientais. Polimorfismos em genes que codificam enzimas do metabolismo modificam correlações de riscos entre exposições e as leucemias. Baseados nas hipóteses que as leucemias na infância têm origem durante a vida intra-uterina, estudos demonstraram associações de exposições maternas durante a gestação à pesticidas e algumas substâncias medicamentosas. Especulamos se os polimorfismos NQO1C609T, PON1Q192R e PON1L55M poderiam influenciar na etiologia das leucemias infantis. O objetivo principal deste estudo foi determinar a freqüência dos polimorfismos nos genes NQO1 e PON1 em crianças com leucemias agudas e suas mães para avaliar as possíveis associações de riscos entre susceptibilidade genética e exposição ambiental. Foram testadas amostras brasileiras de crianças com diagnóstico de leucemia aguda (578); 393 amostras de crianças saudáveis não-sindrômicas (controles), bem como, amostras das respectivas mães. As genotipagens dos genes NQO1 e PON1 foram realizadas através da técnica de discriminação alélica por PCR em tempo real utilizando sondas TaqMan. O genótipo mutante do polimorfismo NQO1C609T confere um risco para o desenvolvimento de leucemias agudas [OR=2,5; IC95%, 1,05-5,88] às crianças com idade ≥24 meses. Na análise estratificada por subtipo leucêmico, nas leucemias mielóides o genótipo mutante confere um risco elevado [OR=5,44; IC95%, 1,08-27,63] nas crianças entre 13-24 meses de idade. A somatória dos genótipos heterozigoto e homozigoto-mutante do NQO1 apresentou uma tendência de risco 2,0 vezes maior da ocorrência nas leucemias com rearranjos do gene MLL [IC95%, 0,94-4,57]. A presença do alelo polimórfico do NQO1C609T nas mães apresenta risco para leucemias agudas pediátricas [OR=1,76; IC95%, 1,03-3,02]. O polimorfismo PON1L55M apresentou associação de risco para LLA, tanto com o genótipo mutante [OR=3,21; IC95%, 1,21-8,51], quanto com a somatória dos genótipos heterozigoto e homozigoto-mutante [OR= 1,94; IC95%, 1,02-3,68]. Este risco aumenta nas crianças com idade entre 13-24 meses [OR=3,22; IC95%, 1,15-8,99]. Foram realizadas análises de exposição materna a pesticidas, antibióticos e infusões de ervas. O polimorfismo do gene NQO1 não mostrou associação de risco, enquanto os polimorfismos do gene PON1 mostraram associações com as exposições e apresentaram magnitudes de risco independentes do tipo de exposição

Pediatric leukemias are heterogeneous diseases which result from the combination of individual genetic susceptibility factors and environmental exposures. Polymorphisms in genes that codify metabolic enzymes alter the risk associations between exposures and leukemias. Based on the prenatal origin of leukemias, studies have demonstrated association between maternal exposures during pregnancy to pesticides or some medicines and childhood leukemia. We speculated whether the polymorphisms NQO1C609T, PON1Q192R and PON1L55M could influence the etiology of the infant leukemias. The main objective of this study was to determine the frequency of these polymorphisms in children with acute leukemia and their mothers to evaluate the possible risk associations between genetic susceptibility and environmental exposures. Samples from children diagnosed with acute leukemia were tested (cases); samples from health children (controls) as well as samples from the respective mothers of both cases and controls were also tested. The genotyping of NQO1 and PON1 was performed using the allelic discrimination real time PCR assay using TaqMan probes. The NQO1C609T mutant genotype was associated with a higher risk of acute leukemia development [OR=2.5; CI95%, 1.05-5.88] in children ≥24 months-old. In the stratified analysis considering the leukemia subtypes, the group of myeloid leukemias presented an increased risk [OR=5.44; CI95%, 1.08-27.63] in children between 13-24 months-old. The sum of NQO1 heterozygous and mutant homozygous alleles showed a trend of 2-fold higher risk of leukemia occurrence in association with MLL gene rearrangements [CI95%, 0.94-4.57]. The polymorphism NQO1C609T within the mothers’ group was associated with childhood leukemias [OR=1.76; CI95%, 1.03-3.02]. The polymorphism PON1L55M presented a risk association with ALL, both considering the homozygous mutant genotype [OR=3.21; CI95%, 1.21-8.51], as well as considering the sum of the heterozygous and the mutant homozygous genotypes [OR= 1.94; CI95%, 1.02-3.68]. This risk increases in children aged between 13-24 months [OR=3.22; CI95%, 1.15-8.99]. The maternal exposures during pregnancy to pesticides, antibiotics and herbal infusions were analyzed in comparison to the genotypes. While no interaction risk associations were observed with the NQO1 polymorphism, the PON1 polymorphisms showed associations with the exposures and presented magnitudes independent of the type of exposure