Effect of nerve growth factor on elderly degenerative knee osteoarthritis pain / 中国骨伤

OBJECTIVE@#To explore effect of nerve growth factor (NGF) antibody on knee osteoarthritis (KOA) pain model was evaluated by in vitro model.@*METHODS@#Thirty male SPF rats aged 28-week-old were divided into blank group (10 rats with anesthesia only). The other 20 rats were with monoiodoacetate (MIA) on the right knee joint to establish pain model of OA, and were randomly divided into control group (injected intraperitoneal injection of normal saline) and treatment group (injected anti-NGF) intraperitoneal after successful modeling, and 10 rats in each group. All rats were received retrograde injection of fluorogold (FG) into the right knee joint. Gait was assessed using catwalk gait analysis system before treatment, 1 and 2 weeks after treatment. Three weeks after treatment, right dorsal root ganglia (DRG) were excised on L4-L6 level, immunostained for calcitonin gene-related peptide (CGRP), and the number of DRGS was counted.@*RESULTS@#In terms of gait analysis using cat track system, duty cycle, swing speed and print area ratio in control and treatment group were significantly reduced compared with blank group (P<0.05). Compared with control group, duty cycle and swing speed of treatment group were significantly improved (P<0.05), and there was no significant difference in print area ratio between treatment group and blank group (P>0.05). The number of FG-labeled DRG neurons in control group was significantly higher than that in treatment group and blank group (P<0.05). The expression of CGRP in control group was up-regulated, and differences were statistically significant compared with treatment group (P<0.05).@*CONCLUSION@#Intraperitoneal injection of anti-NGF antibody inhibited gait injury and upregulation of CGRP in DRG neurons. The results suggest that anti-nerve growth factor therapy may be of value in treating knee pain. NGF may be an important target for the treatment of knee OA pain.

Identification of the metabolites from co-cultures of marine Streptomyces sp. IMB18-531 and Cladosporium sp. IMB19-099 / 药学学报

A new siderophore chelate (1) and 8 known compounds were identified from the liquid co-cultures of the marine-derived Streptomyces sp. IMB18-531 and Cladosporium sp. IMB19-099 by a combination of chromatography methods, including C18 reversed-phase medium pressure chromatography, gel column chromatography and HPLC. Their structures were determined by spectroscopic analysis and chemical methods as aluminioxamine E (1), desferrioxamine E (2), ferrioxamine E (3), terragine E (4), capsimicin (5), cyclo(L-prolinyl-L-tyrosine) (6), anthranilic acid (7), (Z)-14-methylpentadec-9-enoic acid (8), and (Z)-hexadec-8-enoic acid (9). Compound 2 showed inhibitory activities against the expression of liver fibrosis related genes COL1A1, MMP2, and TIMP2. Compounds 5, 8, and 9 displayed antibacterial activities against methicillin-resistant Staphylococcus aureus, S. epidermidis and Bacillus subtilis, with MICs of 16-64 μg·mL-1. Compound 5 showed cytotoxicities against human pancreatic cancer MIA Paca-2 and human colon cancer HT-29 cell lines with IC50 of 2.9 and 6.3 μmol·L-1, respectively.

Discovery of novel KRAS‒PDEδ inhibitors with potent activity in patient-derived human pancreatic tumor xenograft models

KRAS‒PDEδ interaction is revealed as a promising target for suppressing the function of mutant KRAS. The bottleneck in clinical development of PDEδ inhibitors is the poor antitumor activity of known chemotypes. Here, we identified novel spiro-cyclic PDEδ inhibitors with potent antitumor activity both in vitro and in vivo. In particular, compound 36l (K D = 127 ± 16 nmol/L) effectively bound to PDEδ and interfered with KRAS-PDEδ interaction. It influenced the distribution of KRAS in Mia PaCa-2 cells, downregulated the phosphorylation of t-ERK and t-AKT and promoted apoptosis of the cells. The novel inhibitor 36l exhibited significant in vivo antitumor potency in pancreatic cancer patient-derived xenograft (PDX) models. It represents a promising lead compound for investigating the druggability of KRAS‒PDEδ interaction.

Prevalence of anti- "Mia" in blood donors and patients, Zhongshan city / 中国输血杂志

【Objective】 To understand the frequency and significance of anti-" Mia" (anti-" Mia" mixtures of antibodies) in local population in Zhongshan, and the influence of different experimental conditions on the activity of human anti-" Mia" . 【Methods】 The microplate-based agglutination assay and polybrene method were used to screen anti-" Mia" in 3 587 blood samples from voluntary blood donors and patients using O type red blood cells with positive Mia antigen, then.rechecked by tube method and microcolumn gel card method. 【Results】 The frequency of anti-" Mia" was 1.06% (38/3 587), among which 60.5% (23/38) were IgM and 39.5% (15/38) were mixture of IgM and IgG; 0.61% (13/2 135) in local blood donors and 1.72% (25/1 452) in patients(P<0.01). 65.8% (25/38) of the population carrying anti-" Mia" had a history of immunity. 57.9% (22/38) were identified to be anti-" Mur" and 42.1% (16/38) anti-" Mia" using GP.Vw erythrocyte. The appropriate incubation time for anti-" Mia" test was 10 min. 【Conclusion】 The frequency of anti-" Mia" was relatively high among blood donors and patients in Zhongshan, and most of the anti-" Mia" carriers had a history of immunity. Most anti-Mia antibodies were active in saline, and some of them were mixture of IgM and IgG. It may be helpful to include Mia positive red blood cells in the irregular antibody screening cell panel to improve the safety of blood transfusion.

Effect of isocorydine on arrhythmia in rats induced by myocardial ischemia/reperfusion injury / 中国药理学通报

Aim To investigate the effect of isocorydine on arrhythmia in rats induced by myocardial ischemia/reperfusion injury. Methods SD rats were randomly divided into 6 groups: sham group, myocardial ische-mia/reperfusion group, verapamil group and isoc-orydine group of 2. 5 , 5 , 10 mg · kg-1 , each group having 16 rats. Left anterior descending ( LAD ) was tied up to establish the injury model of myocardial is-chemia. ECG was recorded for analysis. The ischemic and infarction area was measured and indexes of SOD, MDA, GSH-Px in the myocardial were determined. Re-sults Isocorydine could significantly reduce the inci-dence of arrhythmia induced by ischemic/reperfusion, including VT, VF;and reduce ischemic and infarction area. Further study demonstrated that isocorydine could increase myocardial SOD and GSH-Px, but de-crease myocardial MDA. Conclusion Isocorydine has a protective effect on the myocardial ischemia/reperfu-sion injury, which might be related to its anti-oxidative function.

Effects of natural eggshell membrane (NEM) on monosodium iodoacetate-induced arthritis in rats / 한국영양학회지

PURPOSE: The aim of this study is to investigate anti-arthritis activity using natural eggshell membrane (NEM). METHODS: NEM was administered at 52 mg/kg, 200 mg/kg, and 400 mg/kg to SD-Rat, where arthritis was induced by monosodium iodoacetate (MIA) at 3 mg. NO production in serum was measured using Griess reagent. Cytokines including IL-1beta, and IL-6 were measured by Luminex and PGE2, MMP-2, MMP-9, TIMP-1, LTB4, and hs-CRP were measured by ELISA. The cartilage of patella volume was examined and 3-D high-resolution reconstructions of the cartilage of patella were obtained using a Micro-CT system. RESULTS: Production of NO, IL-1beta, IL-6, PGE2, MMP-2, MMP-9, TIMP-1, LTB4, and hs-CRP in serum was decreased, respectively, in comparison with control. The cartilage of patella volume increased significantly. In addition, the NEM group showed a decrease in the cartilage of patella, synovial membrane, and transformation of fibrous tissue. CONCLUSION: The results for NEM showed significant anti-arthritis activity. These results may be developed as a raw material for new health food to ease the symptoms mentioned above.

Premio Dr. Antonio Pérez Prado - XIV Congreso Argentino de Medicina Transfusional. Isoinmunización por anti-K1: manejo clínico e inmunohematológico de 30 casos / Dr. Antonio Pérez prado Award - XIV Argentine Congress of Transfusion Medicine. Anti K1 isoimmunization: clinical and immunohematological management of 30 cases

Introducción: La principal causa de anemia fetal es la inmunización por anticuerpos (Acs.) anti-D. La inmunización por anti-K1 es poco frecuente aunque puede producir un cuadro de anemia fetal muy grave. Su incidencia relativa ha aumentado en los últimos años por el aumento de las transfusiones sanguíneas y por disminución de la inmunización anti-D. Presentamos el seguimiento obstétrico e inmunohematológico de 30 casos de gestantes sensibilizadas por anti-Kl. Objetivo: mostrar nuestra experiencia en el manejo clínico e inmunohematológico de gestantes con anti-Kl. Materiales y métodos: Estudio de 30 gestantes con anti-Kl, controladas entre 2005-2012, sobre un N = 48.550 embarazadas. Se estudiaron: compromiso fetal. necesidad de terapéutica intragestacional y posparto, semanas de gestación en el momento del diagnóstico, estado perinatal y complicaciones de las terapéuticas. Además, ABO-Rh, fenotipo materno Rh/Kell, detección e identificación de Acs, título, score, fenotipo Rh/K paterno, seguimiento con ultrasonido para detectar signos de anemia, y desde 2008 control del Pico Sistólico Máximo en arteria cerebral media (PSM-ACM). Resultados: Del total de madres estudiadas, 30 (0,06%) tenían anti-Kl (solo o con anti-D+C, anti-D o anti-Klpa).Títulos de anti-Kl: entre 8 y 8192. De esas solamente 9 (30%) con antecedentes transfusionales. Todos los fetos nacieron vivos. En la mayoría, la inmunización fue leve, sin repercusión en el feto, salvo cuando asociado con Anti-D (quien requirió 5 transfusiones intraútero -TIU- y gammaglobulina intravenosa -lgIV ­entre semana 14 y 32). Todos los recién nacidos (RN) tuvieron peso y apgar adecuados. Hubieron 2 nacimientos prematuros (36 y 34 sem), 1 por diabetes + hipertensión y el otro con Enfermedad Hemolítica Perinatal (EHP) por anti-D+C. Los PSM-ACM fueron adecuados para cada edad gestacional, y nunca superaron el 1,49 múltiplo de la mediana. excepto en 1 paciente con Anti-D...

Introduction: The main cause of fetal anemia is caused by anti-D antibodies (Abs). Anti-K1 immunization is infrequent but can lead to asevere episode of fetal anemia. Its relative incidence has increased in the last few years due to increasing blood transfusions and diminishing anti-D immunization. We hereby present 30 cases of pregnant women with anti-K1. Objective: To show our experience in handling pregnant women with anti-K1.Materials and methods: Retrospective study of 30 pregnant women with anti-K1, under surveillance in the period 2005-2012, N= 48,550 women. Study outcome measures: fetal condition, peripartum (intravenous glob­ulin [IVlg], intrauterine transfusion [IUT]) therapy. Other measures: gestational age at the moment of diagnostic, perinatal status (abortion, fetal death, regular delivery, C­section or need for induction) and therapy complications. Immunohematology tests: ABO-Rh, maternal Rh/Kell phenotype, Ab screening and identification, titer, score,paternal Rh/K phenotype. In all cases of a mother with anti-K1 and a K+ father, confirmed or suspected, a detailed ultrasound follow-up was carried out to detect signs of ane­mia and, from 2008 onwards, a control of middle cerebral artery peak systolic velocity (MCA-PSV). Immunization was rated as low when no antepartum treatment was necessary, and as severe when such treatment was needed. Results: Out of all the studied women, 30 (0,06%) presented anti-K1 (alone or accompanied by anti-D+C, anti-D or anti-K1 pa). Anti-K1 titers: 8 to 8192. Only 9 (30%) patients informed previous transfusional events. AII fetuses were born alive. ln most pregnancies immunization was low, without any effects on the fetus, except for a case related to Anti-D (requiring 5 IUT and Ivlg between weeks 14 and 32). AII newborns (NB) had adequate weight and apgar readings...

Prevalence and Specificity of Unexpected Antibody Using Antibody Screening Test Including Dia and Mia Cells / 대한진단검사의학회지

BACKGROUND: The purpose of this study was to examine the prevalence and distribution of unexpected antibodies detected in the Korean population with race-specific RBC panel cells. In spite of a relatively high prevalence of Dia and Mia antigen phenotype in the Korean and Southeast Asian population, there has been little documented research on the prevalence and clinical significance of anti-Dia and anti-Mia in Korea. METHODS: We analyzed the results of 17, 664 antibody screening tests performed during the recent 30-month period from March 2001 to September 2003. Antibodies were screened and identified by using LISS/Coombs gel card with DiaMed-ID system (DiaMed AG, Cressier, Morat, Switzerland) including Dia and Mia panel cells. RESULTS: The prevalence of unexpected antibodies was 1.2% (214/17, 664); antibodies detected most frequently were anti-Rh (74 patients), followed by anti-Lewis (21 patients) and anti-Dia (15 patients). Out of 6, 345 patients, anti-Mia was detected in three patients (0.047%). Anti-Dia and anti-Mia had the specificity of IgG. Anti-Dia was thought as an immune-mediated antibody, whereas anti-Mia was considered as a mixed type with immune and natural antibodies. CONCLUSIONS: This study shows that anti-Dia and anti-Mia antibodies are detected frequently in the Korean population; hence, it seems that Dia and Mia panel cells should be incorporated into antibody screening panels in Korea for safe transfusion.

Naturally-occurring Anti-Mia(a) in a 16-year-old Korean Man: A Case Study and a Review of the Literature / 대한진단검사의학회지

We report a case of naturally-occurring anti-Miltenberger (anti-Mia(a)) antibody in a 16-year-old man who had never been transfused before. During an operation for a trauma he received 2 units of packed red blood cells. He was negative on an antibody screening test, but positive a week after the surgery when an extended screening test was conducted using blood cells positive for Miltenberger III (Mi.III) phenotype. The Mi.III phenotype is a low incidence antigen among Caucasians, however, it is reported to be relatively high in incidence among people in South-East Asia. Anti-Mia(a) antibodies are clinically significant antibodies that cause hemolytic transfusion reactions (HTRs) and hemolytic disease of the newborns (HDNs). In addition, anti-Mia(a) has a high rate of incidence among Thais, Taiwanese, and Hong Kong Chinese. There has been no particular report on Koreans regarding the incidence of this antibody, it would therefore require further research on the Mi.III phenotype and anti-Mia(a).

A case of Hemolytic Disease of the Newborn due to Anti-Mi a Antibody / 대한수혈학회지

We report a case of hemolytic disease of the newborn caused by anti-Mia (Miltenberger) antibody. Full term male infant was admitted due to hyperbilirubinemia on second day of life. Total serum bilirubin level was 8.6 mg/dL at 12 hours of age and 12.3 mg/dL at 24 hours of age. The blood group of patient and his mother were both RhD positive B type. Direct antiglobulin test was strongly positive in the patient, and testing of maternal serum and patient's serum against a red cell panel including cells known to carry the antigenic determinants of some Miltenberger phenotypes revealed the presence of anti-Mia . Testing of paternal red cells and patient's red cell against anti-Mia serum revealed positive reaction. This report documents the first case of hemolytic disease of the newborn due to anti-Mi a in Korea.