Previous work has shown D1/D2 requisite synergism can still occur in the striatum in the absence of action potentials. Some nonclassical communication such as gap junctions may be allowing the segregated dopamine (DA) receptors to interact to produce stereotyped motor activity. Connexin-32 (Cx32) and connexin-36 (Cx36) were targeted for study due to their abundance in neural tissues and presence in the striatum. Mice lacking either the Cx32 or Cx36 gene and their respective wildtype littermates were compared on a climbing behavior task used to gauge their dopaminergic activity after receiving either saline, D1 agonist, D2 agonist, or both D1 and D2 agonists. The results showed that D1/D2 requisite synergism was still intact in both strains of mice. The Cx32 WT mice displayed significantly greater scores than the KO mice in the D1/D2 treatment. The Cx36 mice did not display a significant genotype difference, but a trend was observed with the KO females having larger scores relative to WT females or to males of either genotype.

Pseudomonas aeruginosa é um patógeno multirresistente capaz de produzir um biofilme protetor contra antibacterianos (ATB). O presente estudo avaliou estratégias terapêuticas contra biofilmes de cepas multirresistentes de P. aeruginosa representativas de clones e/ou genótipos de resistência endêmicos no Brasil. Os biofilmes foram formados in vitro utilizando um modelo adaptado do MBEC Assay e as estratégias terapêuticas utilizaram bacteriófagos líticos, combinação de ATB e/ou uso de força iônica alta (meio FIA). A aplicação de bacteriófagos líticos (φSPM-1) e a combinação de Aztreonam (ATM) e Piperacilina/Tazobactam (PPT), não foram capazes de eliminar o biofilme. Biofilme formado em meio FIA possui CIM similar ao modelo planctônico, tanto para ATM (4 mg/mL) quanto para PPT (16 mg/mL). Ambos os ATB apresentaram CIM reduzida (inferior a 2 mg/mL) quando aplicados em conjunto com meio FIA. Dependendo da concentração de NaCl, a aplicação de meio FIA possui efeito bactericida sobre bactérias planctônicas e efeito bacteriostático sobre biofilmes já formados. / Multidrug-resistant Pseudomonas aeruginosa is a pathogen capable of producing a protective biofilm against antibiotics (ATB). The present study evaluated therapeutic strategies against biofilms of multidrug-resistant strains of P. aeruginosa representative of clones and/or exhibiting resistance genotypes endemic in Brazil. Biofilms were formed in vitro using an adapted model of MBEC Assay and the therapeutic strategies used lytic bacteriophages, combination of ATB and/or use of high ionic strength (HIS medium). The application of lytic bacteriophages (φSPM-1) and the combination of Aztreonam (ATM) and Piperacillin / Tazobactam (PPT) were unable to remove the biofilm. The application of HIS during biofilm formation restored the bacteriostatic effect of both ATM (4 mg/mL) and PPT (16 mg/ml). Both ATB showed reduced MIC values (less than 2 mg/mL) when applied in conjunction with HIS medium. It was shown that HIS has a bacteriostatic or bactericidal effect on planktonic growth, which depend on the NaCl concentration, and bacteriostatic activity against mature biofilm.

Le Gengyun. / Thesis submitted in: December 2002. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 161-182). / Abstracts in English and Chinese. / Abstract --- p.i / Abbreviations --- p.v / Acknowledgements --- p.vii / Publications --- p.viii / Table of Contents --- p.ix / Chapter Chapter 1 --- INTRODUCTION --- p.1 / Chapter 1. --- Vasoconstrictors --- p.1 / Chapter 1.1 --- An overview of vascular smooth muscle contraction --- p.1 / Chapter 1.2 --- Strong and weak vasoconstrictors --- p.5 / Chapter 1.2.1 --- Mechanisms involved in TP receptor vasoconstriction --- p.6 / Chapter 1.2.1.1 --- Brief introduction to the TP receptor --- p.6 / Chapter 1.2.1.2 --- Second messenger systems --- p.6 / Chapter 1.2.1.3 --- G-protein-linked pathways --- p.7 / Chapter 1.2.1.3.1 --- G proteins --- p.7 / Chapter 1.2.1.3.2 --- G-protein-linked TP receptor signal transduction --- p.8 / Chapter 1.2.2 --- Mechanisms involved in α1-adrenoceptor vasoconstriction --- p.8 / Chapter 1.2.2.1 --- Brief introduction to the α1-adrenoceptor --- p.8 / Chapter 1.2.2.2 --- Second messenger systems --- p.9 / Chapter 1.2.2.3 --- G-protein-linked α-adrenoceptor signal transduction --- p.9 / Chapter 1.3 --- Prostanoid EP3 receptor agonists (weak vasoconstrictors) --- p.10 / Chapter 1.3.1 --- Prostanoids --- p.10 / Chapter 1.3.1.1 --- Biochemical characteristics of prostanoids --- p.10 / Chapter 1.3.1.1.1 --- Biosynthesis of prostanoids --- p.10 / Chapter 1.3.1.1.2 --- Metabolism of prostanoids --- p.11 / Chapter 1.3.1.2 --- Prostanoid receptors --- p.13 / Chapter 1.3.1.2.1 --- Structures --- p.13 / Chapter 1.3.1.2.2 --- Current Status of Classification --- p.14 / Chapter 1.3.1.2.3 --- Signal transduction --- p.16 / Chapter 1.3.1.2.4 --- Distribution --- p.18 / Chapter 1.3.1.2.5 --- Physiological functions --- p.18 / Chapter 2. --- Interactions between vasoconstrictors --- p.19 / Chapter 2.1 --- Cross-talk between G-protein-coupled receptors --- p.19 / Chapter 2.1.1 --- Cross-talk between different receptor families --- p.19 / Chapter 2.1.2 --- Cross-talk between subtypes of the same receptor family --- p.21 / Chapter 2.1.3 --- Cross-talk at the effector level --- p.23 / Chapter 2.2 --- Proposed pathways involved in synergistic interactions --- p.24 / Chapter 2.2.1 --- Rho and Rho-associated kinase --- p.24 / Chapter 2.2.1.1 --- Rho family and its identification --- p.24 / Chapter 2.2.1.2 --- Mechanism(s) of Rho contribution in vasoconstriction --- p.25 / Chapter 2.2.1.3 --- Interactions between Rho and other pathways --- p.26 / Chapter 2.2.2 --- Receptor tyrosine kinases --- p.29 / Chapter 2.2.2.1 --- RTK family --- p.29 / Chapter 2.2.2.2 --- Activation of RTKs --- p.29 / Chapter 2.2.2.3 --- Mechanism(s) of RTK contribution in vasoconstriction --- p.30 / Chapter 2.2.2.4 --- Interactions between RTKs and MAPKs --- p.31 / Chapter 2.2.3 --- Mitogen-activated protein kinase --- p.34 / Chapter 2.2.3.1 --- p38 MAPK --- p.35 / Chapter 2.2.3.2 --- JNK MAPK --- p.35 / Chapter 2.2.3.3 --- ERK MAPK --- p.36 / Chapter 2.2.3.4 --- Interactions between MAPK and GPCRs --- p.37 / Chapter Chapter 2 --- FORCE MEASUREMENT SYSTEM --- p.41 / Chapter 1. --- Introduction --- p.41 / Chapter 2. --- Materials --- p.41 / Chapter 2.1 --- Drugs --- p.41 / Chapter 2.2 --- Chemicals --- p.41 / Chapter 2.3 --- Solutions --- p.46 / Chapter 3. --- Methods --- p.46 / Chapter 3.1 --- Isolated smooth muscle preparations and organ bath set-up --- p.46 / Chapter 3.2 --- Data analysis --- p.47 / Chapter Chapter 3 --- VASOCONSTRICTORS AND THEIR INTERACTIONS --- p.48 / Chapter 1. --- Introduction --- p.48 / Chapter 2. --- Materials and Methods --- p.48 / Chapter 2.1 --- Materials --- p.48 / Chapter 2.2 --- Methods --- p.51 / Chapter 2.2.1 --- Isolated tissue preparations --- p.51 / Chapter 2.2.2 --- Experimental protocols --- p.51 / Chapter 2.2.3 --- Statistical analysis --- p.52 / Chapter 3. --- Results --- p.55 / Chapter 3.1 --- Typical vasoconstrictor profiles of agonists --- p.55 / Chapter 3.1.1 --- Sulprostone contraction --- p.55 / Chapter 3.1.2 --- U-46619 contraction --- p.55 / Chapter 3.1.3 --- Phenylephrine contraction --- p.56 / Chapter 3.2 --- Synergistic interactions between sulprostone and strong vasoconstrictors --- p.58 / Chapter 3.2.1 --- Enhancement of U-46619 response by sulprostone --- p.58 / Chapter 3.2.2 --- Enhancement of phenylephrine response by sulprostone --- p.58 / Chapter 3.2.3 --- Enhancement of sulprostone response by phenylephrine --- p.58 / Chapter Chapter 4 --- INVESTIGATION OF PATHWAYS INVOLVED IN EP3 AGONIST- INDUCED VASOCONSTRICTION --- p.64 / Chapter 1. --- Introduction --- p.64 / Chapter 2. --- Materials and methods --- p.65 / Chapter 2.1 --- Materials --- p.65 / Chapter 2.2 --- Methods --- p.65 / Chapter 2.2.1 --- Isolated tissue preparations --- p.65 / Chapter 2.2.2 --- Experimental protocols --- p.65 / Chapter 2.2.3 --- Statistical analysis --- p.69 / Chapter 3. --- Results --- p.70 / Chapter 3.1 --- Effects of tyrosine kinase inhibitors --- p.70 / Chapter 3.2 --- Effects of MAPK inhibitors --- p.82 / Chapter 3.2.1 --- Effects of MAPK inhibitors on U-46619 responses --- p.82 / Chapter 3.2.2 --- Effects of MAPK inhibitors on sulprostone responses --- p.91 / Chapter 3.2.3 --- Effects of MAPK inhibitors on phenylephrine responses --- p.100 / Chapter 3.3 --- Effects of Rho-kinase inhibitors --- p.104 / Chapter Chapter 5 --- TRANSFECTED CELL LINE SYSTEM --- p.111 / Chapter 1. --- Introduction --- p.111 / Chapter 2. --- Materials and methods --- p.114 / Chapter 2.1 --- Materials --- p.114 / Chapter 2.1.1 --- Plasmids and vectors --- p.114 / Chapter 2.1.2 --- Radioactive agents --- p.114 / Chapter 2.1.3 --- Chemicals --- p.114 / Chapter 2.1.4 --- Restriction digest enzymes --- p.115 / Chapter 2.1.5 --- "Culture media, buffers and solutions" --- p.115 / Chapter 2.1.5.1 --- Culture media / Chapter 2.1.5.2 --- Buffers and solutions --- p.115 / Chapter 2.2 --- Methods --- p.116 / Chapter 2.2.1 --- Transfected cell lines --- p.116 / Chapter 2.2.1.1 --- Subcloning of hEP3-1 receptor and hTP receptor cDNA --- p.116 / Chapter 2.2.1.1.1 --- Plasmid recovery / Chapter 2.2.1.1.2 --- Preparation of competent cells --- p.116 / Chapter 2.2.1.1.3 --- Transformation of competent cells --- p.117 / Chapter 2.2.1.1.4 --- Extraction of DNA by QIAGEN Plasmid Mini Kit --- p.117 / Chapter 2.2.1.1.5 --- Restriction enzymes digestion and dephosphorylation --- p.117 / Chapter 2.2.1.1.6 --- DNA recovery and ligation / Chapter 2.2.1.1.7 --- Positive recombinant DNA selection --- p.119 / Chapter 2.2.1.2 --- Cell culture --- p.119 / Chapter 2.2.1.3 --- Transient transfection of CHO cells --- p.121 / Chapter 2.2.1.4 --- Mesurement of adenylate cyclase activity --- p.121 / Chapter 2.2.1.4.1 --- Preparation of columns --- p.121 / Chapter 2.2.1.4.2 --- [3H]-cAMP assays --- p.122 / Chapter 2.2.1.5 --- Measurement of phospholipase C activity --- p.122 / Chapter 2.2.1.5.1 --- Preparation of columns --- p.123 / Chapter 2.2.1.5.2 --- [3H]-inositol phosphate assay --- p.123 / Chapter 2.2.2 --- Data analysis --- p.124 / Chapter 3. --- Results --- p.125 / Chapter 3.1 --- Subcloning of hEP3-1and hTPα receptor cDNA into expression vectors --- p.125 / Chapter 3.2 --- Measurement of cAMP and IP production in transfected CHO cells --- p.133 / Chapter 3.2.1 --- Effect of varying receptor cDNA concentration on agonist-stimulated [3H]-cAMP and [3H]-IP production in transiently transfected CHO cells --- p.133 / Chapter 3.2.2 --- Effect of agonists on intracellular [3H]-IP or [3H]-cAMP productionin CHO cells transfected with hTPα or hEP3-1 --- p.133 / Chapter 3.3 --- Summary --- p.134 / Chapter Chapter 6 --- GENERAL DISCUSSION AND CONCLUSIONS --- p.137 / Chapter 1. --- Vasoconstrictors and their interactions --- p.137 / Chapter 1.1 --- Vasoconstrictors --- p.137 / Chapter 1.2 --- Synergism --- p.138 / Chapter 2. --- Investigation of possible pathways --- p.140 / Chapter 2.1 --- Rho-associated kinase --- p.140 / Chapter 2.2 --- Receptor tyrosine kinase --- p.147 / Chapter 2.3 --- Mitogen-activated protein kinase (MAPK) --- p.151 / Chapter 3. --- Effect of vehicles --- p.155 / Chapter 4. --- Biochemical studies in transfected CHO cells --- p.157 / Chapter 5. --- Conclusions --- p.158 / Appendix I --- p.159 / Buffers and Solutions used in transfected system --- p.159 / Chapter 1. --- Buffers --- p.159 / Chapter 2. --- Solutions --- p.159 / REFERENCES --- p.161

The first harmful effect of caffeine on genetic material was discovered in 1948. The next thirty-three years have given way to public concern and even anxiety over chromosome damage caused by caffeine. More recently, the late 1960’s, concern has arisen over the synergistic characteristic of caffeine.Furosemide, also known as Lasix, is a diuretic and is the drug of choice in treating patients with renal disease. Very little research has been done on the harmful effects furosemide may have on genetic material.This study will investigate the mutagenic potential of caffeine and the mutagenic potential of furosemide. It will also investigate the synergistic effect of caffeine when given with furosemide. Both studies will to done with increasing noses of caffeine and with increasing doses of furosemide.Fifty-six 72-hour chromosome cultures will be set up using fourteen different blood specimens. Four cultures will be made peg- specimen. Specimens numbering one to four will be testing the mutagenic potential of caffeine. Specimens numbering five to eight will be testing the mutagenic potential of furosemide. And, Specimens nine to fourteen will be testing the synergistic effect of caffeine with furosemide.Damage will be assessed by the number of chromosome aberrations, either in the form of gaps or breaks, and the degree of pulverization.Ball State UniversityMuncie, IN 47306

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniversitet, 2004. / Härtill 4 uppsatser.

Thesis (M.S.)--University of Alabama at Birmingham, 2009. / Title from first page of PDF file (viewed on June 11, 2009). Includes bibliographical references (p. 44-54).

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Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / Candida tropicalis à uma levedura diplÃide causadora de infecÃÃes superficiais e/ou sistÃmicas, as quais podem ser adquiridas de maneira endÃgena ou exÃgena e podem acometer diversos ÃrgÃos. No Brasil, dentre as espÃcies de Candida spp., a C.tropicalis à a segunda espÃcie mais comumente isolada e no Cearà à pouco estudada. Nos dias atuais, temos vivenciado um aumento significativo das infecÃÃes fÃngicas invasivas. PorÃm as drogas antifÃngicas disponÃveis no mercado sÃo restritas a um pequeno nÃmero quando comparadas as antibacterianas. Logo, este fato unido ao aumento da frequÃncia de resistÃncia cruzada faz necessÃria a busca por novas estratÃgias terapÃuticas. A amiodarona (AMD) à usada classicamente para tratar pacientes com arritmia. Trabalhos recentes tÃm demonstrado uma ampla atividade antifÃngica desta droga quando associado ao fluconazol (FLC). No presente estudo induzimos resistÃncia em sete cepas de Candida tropicalis e avaliamos um eventual sinergismo entre FLC e AMD. A avaliaÃÃo da interaÃÃo das drogas foi determinada atravÃs do cÃlculo da Fractionary Inhibitory Concentration (FICI) e por meio da tÃcnica de citometria de fluxo, onde tambÃm avaliamos o provÃvel mecanismo de aÃÃo desse sinergismo. Os isolados utilizados no estudo pertencem ao LaboratÃrio de BioprospecÃÃo Experimental em Leveduras (LABEL) da UFC. Para o cumprimento da metodologia, as cepas foram recuperadas do estoque e identificadas por biologia molecular. A induÃÃo foi realizada adaptando-se o protocolo de Pinto e Silva (2009). Os testes de sensibilidade foram realizados utilizando-se o teste de microdiluiÃÃo em caldo padronizado pelo CLSI, segundo o documento M27-A3. Para avaliar o sinergismo utilizou-se a tÃcnica do checkboard. Por fim, para verificar o possÃvel mecanismo de aÃÃo do sinergismo, determinamos a integridade de membrana, potencial transmembrana mitocondrial, formaÃÃo de espÃcies reativas de oxigÃnio (ROS), teste do cometa, anÃlise da oxidaÃÃo de bases purinas e caspases. As cepas de C.tropicalis apÃs ~100 dias atingiram um CIM > 64Âg/mL. Os testes de sensibilidade apresentaram CIM > 64Âg/mL tanto para o FLC como para AMD. Das cepas testadas, seis apresentaram sinergismo. O tratamento FLC+AMD alterou a integridade da membrana plasmÃtica e mitocondrial, aumentou os nÃveis de ROS intracelularmente, causou danos ao DNA e, consequentemente, conduziu morte celular por apoptose. / Candida tropicalis is a diploid yeast causing superficial infections and / or systemic, which can be acquired endogenously or exogenously and can affect several organs. In Brazil, among the species of Candida spp. The C.tropicalis is the second most common species isolated in Cearà and is rarely studied. Nowadays, we have experienced a significant increase in invasive fungal infections. But antifungal drugs on the market are restricted to a small number when compared to the antibacterial. Therefore, this fact coupled with the increased frequency of cross-resistance is necessary to search for new therapeutic strategies. Amiodarone (AMD) is traditionally used to treat patients with arrhythmia. Recent studies have shown a broad antifungal activity of this drug when combined with fluconazole (FLC). In the present study we induced resistance in seven strains of Candida tropicalis and evaluate a possible synergism between FLC and AMD. The evaluation of the interaction of the drugs was determined by calculating the Fractionary Inhibitory Concentration (FICI) and by flow cytometry, where we also evaluated the likely mechanism of action of this synergism. The isolates used in this study belong to the Laboratory of Experimental Bioprospecting in yeast (LABEL) the UFC. For the fulfillment of the methodology, the strains were recovered from stock and identified by molecular biology. The induction was carried out adapting the protocol of Pinto and Silva (2009). Sensitivity tests were performed using the broth microdilution test standardized by the CLSI, the document M27-A3. To evaluate the synergism used the technique of checkboard. Finally, to determine the possible mechanism of action of synergism, we determine the membrane integrity, mitochondrial transmembrane potential, formation of reactive oxygen species (ROS), comet assay, analysis of the oxidation of purine bases and caspases. Strains C.tropicalis after ~ 100 days reached an MIC> 64μg/mL. The sensitivity tests were MIC> 64μg/mL both the FLC as AMD. Of the strains tested, six showed synergism. The treatment changed the FLC + AMD plasma membrane integrity and mitochondrial increased levels of intracellular ROS, cause DNA damage and therefore led cell death by apoptosis.

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / Este trabalho teve como objetivo determinar o efeito sinergÃstico entre a aplicaÃÃo de sal comum à Ãgua e a taxa de aeraÃÃo suplementar, na remediaÃÃo dos efeitos tÃxicos da amÃnia, em juvenis de tilÃpia do Nilo na fase de recria, em ambiente de cultivo indoor e outdoor. O trabalho foi realizado no LaboratÃrio de CiÃncias e Tecnologia AquÃcola - LCTA. Foram realizados dois experimentos um indoor e outro outdoor. No experimento indoor foram utilizados juvenis de tilÃpia do Nilo, Oreochromis niloticus, estocados em 30 tanques de polietileno com volume total de 100 L, na densidade de 3 juvenis tanque-1. Sendo constituÃdos cinco diferentes grupos experimentais: à + F (sem sal e aeraÃÃo fraca); Ã+ I (sem sal e aeraÃÃo intensa); S+F (com sal e aeraÃÃo fraca); S+M (com sal e aeraÃÃo moderada) e S+I (com sal e aeraÃÃo intensa) e um grupo controle Ã+M (sem sal e aeraÃÃo moderada), cada um com cinco tanques e em delineamento inteiramente casualizado. No cultivo outdoor foram utilizados juvenis de tilÃpia do Nilo, Oreochromis niloticus, estocados em 20 tanques de polietileno com volume total de 250 L, na densidade de 6 juvenis tanque-1. Sendo constituÃdos quatro diferentes grupos experimentais (sem sal + sem ar; sem sal + com ar; com sal + sem ar e com sal + com ar), cada um com 5 tanques e em delineamento inteiramente casualizado. Cada experimento teve a duraÃÃo de 8 semanas, os dados indicam que houve diferenÃa no desempenho zootÃcnico de juvenis de tilÃpia do Nilo quando foram submetidos à aeraÃÃo suplementar diurna e aplicaÃÃo de sal. Foi comprovada a aÃÃo do sal no alÃvio do estresse (devido a elevadas concentraÃÃes de nitrogÃnio amoniacal total e nitrito na Ãgua) e consequentemente no conforto da tilÃpia do Nilo. Dessa forma os peixes se alimentaram e aproveitaram melhor o alimento. Houve sinergismo entre a aplicaÃÃo de sal comum e a aeraÃÃo suplementar diurna na remediaÃÃo da toxicidade crÃnica de nitrogÃnio amoniacal total e nitrito em juvenis de tilÃpia do Nilo. / The present work aimed to determine the synergistic effect between the application of common salt to the water and aeration rate further in the remediation of the toxic effects of ammonia on juvenile Nile tilapia at growing in an environment of indoor and outdoor cultivation. This work was performed at the Laboratory of Aquaculture Science and Technology-LCTA. In this work, two experiments were conducted, the indoor and outdoor. In indoor cultivation was used fingerlings Nile tilapia, Oreochromos niloticus stocked in 30 polyethylene tanks with a total volume of 100L, the density of juvenile 3-1 tanks. Being made five different experimental groups ((à + F, Ã+ I, S+F, S+M e S+I)) and a control group (à + M), each with five replicates. In a completely randomized design. In outdoor cultivation was used juvenile Nile tilapia, Oreochromos niloticus stocked in 20 polyethylene tanks with a total volume of 250L, the density of juvenile tanks 6-1. Since four different experimental groups consisting of (without salt + no air, without salt + with air, with salt + no air, with salt + with air), each with five replicates. Each experiment lasted for 8 weeks. No difference in growth performance of juvenile Nile tilapia when treatments are subjected to supplementary daytime aeration and application of salt. Was demonstrated the action of the salt in relieving stress (due to high concentrations of NAT and nitrite in the water) and consequently in the comfort of Nile tilapia. Thus the fish fed and enjoyed the best food. There is synergism between the application of common salt and supplemental aeration daytime in the remediation of chronic toxicity of NAT and nitrite in juvenile Nile tilapia.

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