ering and ApplicationsComputer Engineering and ApplicationsCo

椎-基动脉供血不足(vertebrobasifarinsufficiency,V BI)是指椎-基动脉由于各种原因引起的形态、机能的异常,产生相应灌流区供血不足,引起眩晕、头晕、复视、共济失调、偏瘫、视力及视野改变等临床症状,而眩晕、头晕为其主要症状。我们采用盐酸倍司汀联用参麦注射液治疗椎-基动     

Golimumab and immunogenicity? 2010 and beyond

Immunogenicity is a frequent adverse event observed with biological agents' therapy. Challenges of management in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis treated with golimumab, an anti-TNF-alpha blocker, include limited generation of antibodies like anti-nuclear, anti-golimumab, and anti-double stranded DNA antibodies. We conducted here a meta-analysis study in order to evaluate and compare the newly generated antibody levels after golimumab therapy. The examination of original clinical trials revealed that their levels were neither higher nor significant. Moreover, no evident associations between the induced-antibodies and lupus-like syndromes and/or infusion site reaction were reported. The reduced patients cohort and the absence of systematic newly generated antibodies follow-up might be implicated in the difficulty to evaluate their risk in delaying diseases therapy, and/or predicting for their worse prognosis. Hence, further studies are required to ascertain the real impact of the induced antibodies after golimumab's therapy.     

Biomolecular structure and dynamics—experiment and theory

Biological macromolecules are complex systems and in order to understand their inner workings we need information from many sources. In this review we present some of the underlying principles for current methods of choice for structural and dynamical studies of biological macromolecules. Interplay between these disciplines—X-ray diffraction, nuclear magnetic resonance spectroscopy and theoretical calculations—has been extremely fruitful and our knowledge in this area of bioscience is rapidly increasing due to this cross-fertilization. While structural aspects of proteins are increasingly well studied and understood we do however still need to put more emphasis on their dynamical properties.     

Toxicology and Genetic Susceptibility of Drugs and Pollutant

S21Possibleinvolvementofhereditaryfactors intheriskmodulationofarseniasisintwoethnic clansexposedtoindoorcombustionofhigharse niccoal LINGuo Fang1,DUHui2,CHENJi Gang3,LU Hong Chao2,GUOWei Chao1,ZHANGXin Jiang4,SHENJian Hua1(1.ShanghaiInstituteforBiologicalSciences,Institute ofPlantPhysiologyandEcology,ChineseAcademyof Sciences,Shanghai200032,China;2.Prefecture CenterforDiseasePreventionandControl,Guiyang562400,China;3.MunicipalCenterforDiseasePre ventionandControl,Shang…     

Immunotoxicity and Neurotoxicity of Pharmaceuticals and Environmental Toxic Substances

W31ICHS8Guideline:immunotoxicitystud iesforhumanpharmaceuticals JSAWADA(NationalInstituteofHealthSciences,Tokyo,Japan)Toxicitytotheimmunesystemencompassessup pressionorenhancementoftheimmuneresponse.Sup pressionoftheimmuneresponsecanleadtodecreased hostresistancetoinfectiousagentsortumorcells.En hancingtheimmuneresponsecanexaggerateautoim munediseasesorhypersensitivity.Therfore,evaluationofpotentialadverseeffectsofhumanpharmaceuticals ontheimmunesystemshouldbeincorporatedinto standardd…     

The ethics and practice of authorship and peer review

Ｏｎｃｅａｃｌｉｎｉｃａｌｔｒｉａｌｉｓｃｏｍｐｌｅｔｅｄ，ｉｔｍｕｓｔｂｅｐｕｂｌｉｓｈｅｄｉｎｏｒｄｅｒｆｏｒｏｔｈｅｒｓｔｏｋｎｏｗｏｆｉｔｓｒｅｓｕｌｔｓ．Ｐｒｉｍａｒｙｓｏｕｒｃｅ，ｐｅｒｒｅｖｉｅｗｅｄｍｅｄｉｃａｌｊｏｕｒｎａｌｓａｒ...     

Toxicogenomics and Proteomics

W1:ToxicogenomicsandProteomics W11Differentialgeneexpressionprofilesofacuteandchronicinjuryandrecoveryinratliv ersteatosis fibrosis/cirrhosismodel HeekyoungCHUNG(KST)W12SNPsinCYP450s:apreliminaryphar macogenomicstudyinaChinesepopulation WENSi Yuan1,CHENKun2,XULi1,LIJian2,WANGRui2,WANGSheng Qi1(1.BeijingInstituteofRadiationMedicine,2.Beijing301GeneralHospital,Beijing100039,China)Pharmacogenomicswasestablishedonthefactthat certaingeneticpolymorphismsmaycausesignificantly di…     

Medical Toxicology and Public Health—Update on Research and Activities at the Centers for Disease Control and Prevention and the Agency for Toxic Substances and Disease Registry

Evidence suggests that in-utero exposure to environmental chemicals, such as persistent organic pollutants (POPs), heavy metals, and radionuclides, that might bioaccumulate in the mother may increase a newborn's risk of adverse developmental, neurological, and immunologic effects. Chemical contamination of bodies of water and strong ocean currents worldwide can drive these chemicals from lower latitudes to Arctic waters where they accumulate in common traditional subsistence foods. In response to concerns of the people from Alaska of the effects of bio-accumulated chemicals on their children, the Maternal Organics Monitoring Study(MOMS) was developed. The objective of the study was to assess the risks and benefits associated with the population's subsistence diet. Data analysis of biological samples at the CDC's NCEH laboratory and maternal questionnaires is ongoing. Results will be provided to Alaska Native communities to help support public health actions and inform future interventions and research.     

Acid–base equilibria and solubility of loratadine and desloratadine in water and micellar media

Acid–base equilibria in homogeneous and heterogeneous systems of two antihistaminics, loratadine and desloratadine were studied spectrophotometrically in Britton–Robinson’s buffer at 25 °C. Acidity constant of loratadine was found to be pK_a 5.25 and those of desloratadine pK_a1 4.41 and pK_a2 9.97. The values of intrinsic solubilities of loratadine and desloratadine were 8.65 × 10⁻⁶ M and 3.82 × 10⁻⁴ M, respectively. Based on the pK_a values and intrinsic solubilities, solubility curves of these two drugs as a function of pH were calculated. The effects of anionic, cationic and non-ionic surfactants applied in the concentration exceeding critical micelle concentration (cmc) on acid–base properties of loratadine and desloratadine, as well as on intrinsic solubility of loratadine were also examined. The results revealed a shift of pK_a values in micellar media comparing to the values obtained in water. These shifts (ΔpK_a) ranged from −2.24 to +1.24.     

Opioid and neuroHIV Comorbidity – Current and Future Perspectives

Journal of Neuroimmune Pharmacology - With the current national opioid crisis, it is critical to examine the mechanisms underlying pathophysiologic interactions between human immunodeficiency virus...     

Epidemiology and prevalence of extended-spectrum β-lactamase- and carbapenemase-producing Enterobacteriaceae in humans,animals and the environment in West and Central Africa

Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) and carbapenemase-producing Enterobacteriaceae (CPE) are widespread. Here we used the ‘One Health’ approach to determine knowledge gaps on ESBL-E and CPE in West and Central Africa. We searched all articles on ESBL-E and CPE in these African regions published in PubMed, African Journals Online and Google Scholar from 2000 onwards. Among the 1201 articles retrieved, we selected 165 studies (West Africa, 118; Central Africa, 47) with data from 22 of the 26 West and Central Africa countries. Regarding the settings, 136 articles focused only on humans (carriage and/or infection), 6 articles on humans and animals, 13 on animals, 1 on humans and the environment, 8 on the environment and 1 on humans, animals and environments. ESBL-E prevalence ranged from 11–72% in humans and 7–79% in aquatic environments (wastewater). In animals, ESBL-E prevalence hugely varied: 0% in cattle, 11–36% in chickens, 20% in rats, 21–71% in pigs and 32–75% in dogs. The bla_CTX-M-15 gene was the predominant ESBL-encoding gene and was associated with plasmids of incompatibility groups F, H, K, Y, N, I1 and R. CPE were studied only in humans. Class B metallo-β-lactamases (NDM) and class D oxacillinases (OXA-48 and OXA-181) were the most common carbapenemases. Our results show major knowledge gaps, particularly on ESBL and CPE in animals and the environment, that might limit antimicrobial resistance management in these regions. The results also emphasise the urgent need to improve active surveillance programmes in each country and to support antimicrobial stewardship.     

Expression and significance of IGF-Ⅱand VEGF in hepatocellular carcinoma

目的 检测肝癌(HCC)患者组织中IGF-Ⅱ、血管内皮生长因子 (VEGF)的表达及临床意义.方法 采用免疫组织化学染色方法 检测HCC及癌旁组织中IGF-Ⅱ、VEGF蛋白表达水平.结果 HCC及癌旁组织IGF-Ⅱ蛋白阳性表达率分别为55%(22/40)、12.5%(5/40),VEGF蛋白阳性表达率分别为62.5%(25/40)、12.5%(5/40),HCC组织中IGF-Ⅱ、VEGF蛋白表达均显著高于癌旁组织(P<0.05),且IGF-Ⅱ、VEGF表达呈明显正相关(r=0.59,P<0.05).IGF-Ⅱ、VEGF表达与患者的年龄、性别、肿瘤大小无关,但与肿瘤的组织学分级、是否侵及包膜及有无癌栓密切相关.结论 与癌旁组织比较,HCC组织中IGF-Ⅱ、VEGF呈现高表达,提示IGF-Ⅱ、VEGF参与了HCC的发生发展过程,可能与HCC的生长和增殖有关.     

Huperzine-A and ginkgolides inhibit nitric oxide production from rat and human astrocytoma and block its neurotoxicity

While the complex reasons causing Alzheimer's disease (AD) remain unclear, pre-inflammatory cytokines, complement proteins, activated glia, and nitric oxide (NO) are proposed playing important roles in AD.Using cultured rat C6 and human BT325 astrocytoma cell lines as model of astrocytes, and human neuroblastoma SK-N-SH cell line as target cell in the potential neurotoxicity,the effects of lipopolysaccharide(LPS) and proinflammatory cytokines on NO production from cultured astrocytes, the effects of NO on the proliferation and apoptosis of     

“Anxiolytic” and “anxiogenic” benzodiazepines and β-carbolines: effects on aggressive and social behavior in rats and squirrel monkeys

Ethopharmacological studies on the behavior of socially housed rats and squirrel monkeys were conducted to explore the role of the benzodiazepine GABA_A-coupled ionophore receptor complex in aggressive and social interactions. Benzodiazepine receptor (BZR) antagonists, ZK 93426 (1–10 mg/kg) and flumazenil (3–10 mg/kg), the partial agonist, ZK 91296 (1–10 mg/kg) and the partial inverse agonists RO 15-4513 (0.3–10 mg/kg), were administered to (1) squirrel monkeys prior to 1 h focal observations within established social groups or to (2) resident male rats before confrontations with a naive male intruder in their home cage for 5 min. Aggression was modified in a similar manner in both species, although squirrel monkeys were more sensitive to BZR challenges. Specifically, resident male rats showed dose dependent reductions in attack bites directed at intruder males that were significant at the highest dose of ZK 93426 (10 mg/kg). In squirrel monkeys, ZK 93426 (3 and 10 mg/kg) reduced aggressive grasps, threats and displays, as well as reducing the duration of being the target of aggression from untreated group members (1–10 mg/kg). The BZR partial agonist, ZK 91296 and the antagonist, flumazenil produced few effects on social behavior, low and high intensity aggression and motor activity in both species. Flumazenil (10–30 mg/kg) and ZK 91296 (10 mg/kg), but not ZK 93426, produced significant increases in foraging and feeding behaviors in squirrel monkeys. The hyperphagic effects of ZK 91296 and flumazenil, that are typical of BZR agonists compounds, were not observed in rats. Similarly, the inverse agonist-like reductions in social interactions produced by ZK 93426 (3–10 mg/kg) were observed only in squirrel monkeys. The partial inverse agonist Ro 15-4513 reduced aggression in rats, but low doses (1 mg/kg) produced tremors or seizures in 80% of the monkeys tested. Decreases in aggressive and social behaviors are often interpreted to reflect anxiogenic drug properties, whereas increased feeding has been associated with anxiolytic actions. The concurrent emergence of these apparent opposites suggests independent actions on social and alimentary functions.     

The solute carrier transporters and the brain:Physiological and pharmacological implications

Solute carriers(SLCs)are the largest family of transmembrane transporters that determine the exchange of various substances,including nutrients,ions,metabolites,and drugs across biological membranes.To date,the presence of about 287 SLC genes have been identified in the brain,among which mutations or the resultant dysfunctions of 71 SLC genes have been reported to be correlated with human brain disorders.Although increasing interest in SLCs have focused on drug development,SLCs are currently still under-explored as drug targets,especially in the brain.We summarize the main substrates and functions of SLCs that are expressed in the brain,with an emphasis on selected SLCs that are important physiologically,pathologically,and pharmacologically in the blood-brain barrier,astrocytes,and neurons.Evidence suggests that a fraction of SLCs are regulated along with the occurrences of brain disorders,among which epilepsy,neurodegenerative diseases,and autism are representative.Given the review of SLCs involved in the onset and procession of brain disorders,we hope these SLCs will be screened as promising drug targets to improve drug delivery to the brain.     

Bioavailability and disposition of ‘H-solanine in rat and hamster

1. The toxicokinetics of [³H]-α-solanine after oral (p.o.) and intravenous (i.v.) administration in rat and hamster were studied, in order to decide which is the most appropriate model in risk assessment studies. The i.v. Dose was 54 βg/kg; the oral dose was 170 βg/kg.

2. After i.v. Administration, the toxicokinetics of total radioactivity in blood were comparable in rat and hamster. However, the clearance of total radioactivity from plasma was more effective in rat than in hamster. The half-lives of distribution and of the terminal phase of unchanged α-solanine were not different between rat and hamster, whereas the systemic and metabolic clearance were, respectively, about 1.6 and 2.7 times higher in rat than in hamster. The clearance of unchanged α-solanine is more effective than of total radioactivity.

3. After p.o. Administration in rat and hamster, the mean bioavailability of total radioactivity is about 29 and 57%, respectively. The bioavailability of unchanged α-solanine is only 1.6 and 3.2%, respectively, when compared with i.v. administration.

4. T_1/2el of α-solanine after p.o. Administration was in rats a factor of four and in hamsters a factor of two shorter than after i.v. Administration. A strong retention of radioactivity was seen in the hamsters after p.o. Administration; only 40% of the dose was excreted within 7 days versus 90% in rat.

5. Based on these and toxicological data from literature, it was decided that the hamster is a more appropriate model in (sub) chronic toxicity studies with α-solanine than the rat.     

Detection and quantitation of β-blockers in plasma and urine

β-blockers are a class of antihypertensive drugs that are used for the management of cardiac arrhythmias, cardioprotection after myocardial infarction (heart attack) and hypertension. They have revolutionized the medical management of angina pectoris and are recommended as first-line agents by national and international guidelines. Although β-blockers are still the cornerstone for the treatment of heart failure, some of the drugs in this category are prohibited in several sports requiring vehicle control and bodily movements as they reduce heart rate and tremors, and improve performance. As a result, urine analysis of β-blockers is mandatory in doping control and toxicological screening. The determination of plasma levels of β-blockers helps to ensure noncompliance in patients with persistent hypertonia to confirm the diagnosis of β-blocker poisoning and for therapeutic drug monitoring. This review provides a comprehensive account of various analytical methods developed for detection and quantitation of β-blockers in plasma and urine.