Orientador: Eduardo Dias de Andrade / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-03T16:34:47Z (GMT). No. of bitstreams: 1 Abrahao_JoaoMigueldeBarros_D.pdf: 1096955 bytes, checksum: 5d94a7ca751633e0a5eaa63b6819accf (MD5) Previous issue date: 1994 / Resumo: Este trabalho teve por objetivo avaliar os efeitos de uma tríade medicamentosa sobre os valores de pressão arterial sanguínea (PA) e frequência cardíaca (FC) em pacientes com indicação da exodontia de terceiros molares mandibulares inclusos. Para tanto foram selecionados 17 pacientes, de ambos os sexos, na faixa etária de 17 a 23 anos e normotensos, que foram tratados com o diazepam e a dexametasona, nas doses de 5 mg e 4 mg, respectivamente, 1 hora antes do procedimento cirúrgico, associadas à um anestésico local de longa duração (bupivacaína a 0,5% com adrenalina 1:200.000). As avaliações de PA e FC foram realizadas em 5 tempos distintos, ou seja, na semana anterior e no dia da cirurgia, com o paciente em repouso 60 minutos após a administração do diazepam e da dexametasona, 10 minutos após a injeção do anestésico local e após o término da intervenção cirúrgica. Os resultados mostraram que os valores médios da pressão arterial sanguínea (sistólíca e diastólica), bem como da frequência cardíaca, situaram-se dentro da faixa de normalidade biológica, durante todo o período experimental / Abstract: The aim of this study is to evaluate the effects of three drugs over blood pressure and heart rate in subjects submitted to impacted third molar removal. For this purpose, 17 patients, both sex, aged between 17 and 23 years, normotensive, were selected and treated with diazepan and dexametasone by single dose of 5mg and 4mg, respectively, one hour before the surgical procedure, associated a long-lasting local anaesthetic (bupivacaine 0.5% with epinephrine 1:200,000). The blood pressure and heart rate was measured in 5 different times, a week before, on the surgery day, with patient in rest position, 60 minutes after diazepan and dexametasone administration, 10 minutes after local anaesthetic injection, and at the end of the surgery. The results showed that the mean blood pressure (systolic and diastolic), heart rate within physiological values during the experimental phase / Doutorado / Farmacologia / Doutor em Ciências

Orientador : Thales Rocha de Mattos Filho / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-07-14T01:49:19Z (GMT). No. of bitstreams: 1 KozlowskiJunior_VitoldoAntonio_M.pdf: 2863936 bytes, checksum: 049b9bdb12aa918a0cd3f2e417f9291a (MD5) Previous issue date: 1991 / Resumo: Ratos albinos machos foram utilizados para investigar os efeitos de antagonista específico de receptores H1 perifericos ,Terfenadina e receptoresH2' Ciroetidina sobre a enzima ?-glutamiltransferase( ?-GT) DO soro destes animais durante a regeneração hepática após hepatectomia parcial. 67 ratos divididos em três grupos foram sacrificados respectiva- mente 6 h, 24 h e 360 h após a tecnica cirurgica. Cada grupo contendo 4 sub-grupos receberam doses de Terfenadina (2 mg/Kg/dia), Cimetidina (20 ms/Kg/dia), Terfenadina (20mg/Kg/dia)+ Cimetidina (20mg/Kg/dia) e NaCl 0,9;% (Controle), intraperitonealmente durante o tempo do experimento. Os resultados obtidos sugerem que o antagonista de receptor H1 periférico- Terfenadina, induziu a atividade da ?-glutamiltransferase no soro de ratos, 360 h após hepatectomia parcial / Abstract: Adult male albino rats (Wistar strain) were used to investigate the effecte of selective antagonist of only peripheral histamine H1-receptors, Terfenadine and histamine H2-receptors antagonist, Cimetidine on the serum activity of the enzyme y-glutamiltransferase( ? -GT) during liver regeneration after partial hepatectomy. Sixty-seven animals were randomly divided into three groups and were 'sacrificed respectively, 6 h, 24 h and 360 h postoperatively. Each group was divided into four sub-groups that received ' doses of Terfenadine (2 mg/Kg,/day),Cimetidine (, 20 mg/Kg/day), Terfenadine (2mg /Kg /day) + Cimetidine (20 mg/Kg/ day) and NaCl 0,9 % (Control), intraperitoneally during the experimentation. The results obtained suggested that peri - pheral histamine Hl- receptor antagonist - Terfenadine, induced the 1(-glutamiltransferase serum activity in rats.360 h after partial hepatectomy / Mestrado / Farmacologia / Mestre em Ciências

Orientador : Minoru Sakate / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-07-14T03:28:58Z (GMT). No. of bitstreams: 1 Barros_PedroPaulo_M.pdf: 1462394 bytes, checksum: f5dad0288a00d6f051a2581f71a86ea4 (MD5) Previous issue date: 1976 / Resumo: Não informado. / Abstract: Not informed. / Mestrado

Orientador : Decio Teixeira / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-07-14T12:03:49Z (GMT). No. of bitstreams: 1 Boaventura_MiriamCampos_D.pdf: 2711739 bytes, checksum: b94ad0d6136eef7f879c8c54a09ab7f0 (MD5) Previous issue date: 1988 / Resumo: o presente trabalho foi realizado com a finalidade de se verificar "In Vitro~, os eventuais efeitos da Sialotoxina I (SI), sobre a incorporação de glicose e o consumo de oxigênio pelo diafragma de ,ratos. Foram utilizados 102 ratos machos (Rattus , norvergicus, albinus, Wistar),' com 2 a 3 meses de idade, pesando entre 150 e 200 gramas...Observação: O resumo, na integra, podera ser visualizado no texto completo da tese digital / Abstract: Not informed. / Doutorado / Farmacologia / Doutor em Ciências

Orientador: Armando Octavio Ramos / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-07-14T16:03:49Z (GMT). No. of bitstreams: 1 Massini_Nelson_M.pdf: 1402660 bytes, checksum: 94c0fafc773b9177245bd5028edc3d25 (MD5) Previous issue date: 1975 / Resumo: Não informado / Abstract: Not informed. / Mestrado / Mestre em Farmacologia

Orientadores : Samir Tufic Arbex, Gloria Emilia Petto de Souza / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-07-13T23:11:30Z (GMT). No. of bitstreams: 1 Bisson_MarceloPolacow_M.pdf: 2951044 bytes, checksum: 514a26fd9aad87cfbad7326397a4e525 (MD5) Previous issue date: 1991 / Resumo: o presente trabalho leve como finalidade. veriricar alguns aspectos relacionados à posslvel ação analgésica central do paracetamol, em roedores. Para isto foram empregados quatro modelos de estudo distintos: 1 - Teste de contorção induzida pelo ácido acético administrado intraperitonealmente. 2 - Teste de contorção induzida pela prostaciclina sintética administrada intraperitonealmente. 3 - Teste de estimulação térmica Tail-Flick. 4 - Teste de estimulação térmica placa-quente. Os resultados obtidos demonstraram que o paracetamol inibiu o número de contorções induzida pelo ácido acético e pela prostaciclina sintética, de maneira dose dependente, sendo que na maior dose testada de 315mg/kg á porcentagem de inibição foi de 89.4% e 82.1% respectivamente. Da mesma forma. esta droga, aumentou o tempo de latência nos testes Tail-Flick e placa-quente. de maneira dose dependente. sendo que na maior dose testada de 316 mg/kg a porcentagem do máximo efeito possível foi de 84% e 60%. respectivamente. e conseguidos no tempo de 90 minutos após a sua administração. A partir disso, pode-se concluir que o paracetamol, nas doses empregadas em roedores, demonstrou ser capaz de causar analgesia por um mecanismo central / Abstract: This work had the purpose of verifying several aspects related the possible analgesia by central action of Paracetamol in rodents. In order to achieve that purpose four distint sludy models were employed: 1 - Writhing test induced by i. p.. injection of acetic acid. 2 - Writhing test induced by i.p.injection of synthetic prostaciclin. 3 - Thermal stimulation test. Tail-Flick. 4 - Thermal stimulation test.- Hot-Plate. The results have showed that the paracetamol, has inhibit the abdominal constriction response induced by acetic acid and synthetic proslaciclin of dose-dependent manner, being the biggest testing dose of 315 mg/kg, the percentage of inhibition was 89.4% and 82.1% respectively. In the same way this , drug increased the latency time in the Tail-Flick and Hot-Plate tests, of dose-dependent manne, being the biggest testing dose of 315 mg/kg, the percentage of maximal possible effect was 84% and 5O%, respectively, and achieved in the time of 90 minutes after it administration. From t.hese results. we can conclud that the paracetamol in the used doses in rodents, was able te produce analgesia by a central action / Mestrado

Orientador : Luis Alberto Magna / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-07-13T23:00:06Z (GMT). No. of bitstreams: 1 Hofstatter_EduardoAlexandre_M.pdf: 2870890 bytes, checksum: dab27479fd048736f5e693a231bad23c (MD5) Previous issue date: 1991 / Mestrado / Genetica / Mestre em Ciências Biológicas

Orientador : Gilberto de Nucci / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-07-17T08:03:54Z (GMT). No. of bitstreams: 1 Landucci_ElenCristinaTeizem_M.pdf: 1201641 bytes, checksum: 4dfd3d2cfec465ae96a708250111e553 (MD5) Previous issue date: 1992 / Resumo: A crotoxina, o componente mais tóxico isolado do veneno de Crotalus durissus terrificus, é um complexo proteico reversível composto por um peptídeo ácido, não tóxico e sem ativadade enzimática (crotapotina) e um componente básico, responsável pela toxicidade do complexo, a fosfolipase A2 (PLA2). Sabendo-se que várias proteínas isoladas a partir de venenos interferem na coagulação sanguínea e agregação plaquetária, o objetivo deste trabalho foi o estudo da atividade da crotoxina sobre a agregação plaquetária. A crotoxina foi isolada através de gel filtração do veneno bruto em uma coluna de Sephadex G-75, eluída com tampão bicarbonato de amônio (0.1 M; pH 8.0). A agregação das plaquetas humanas lavadas foi monitorada utilizando-se um agregômetro Payton e a liberação de TXA2 foi medida através de radioimunoensaio (RIA). O fracionamento de 100 mg de veneno, resultou em três principais picos, sendo o segundo pico correspondente à crotoxina. O grau de pureza da crotoxina foi confirmado, utilizando-se o método de cromatografia de alto desempenho (HPLC) através de uma coluna C 18 µ Bondapack. Crotoxina (15-50 µg/ml), produz uma agregacão de plaquetas lavadas de modo dose-dependente e irreversível, agregação esta inibida por uma pré-incubação da suspensão de plaquetas com SNP (500 µM) ou lIoprost (100 nM). A crotoxina também induz a liberação de TXB2 (207±8 ng/ml, n=6). Nossos resultados demonstram que a crotoxina induz a agregação de plaquetas humanas lavadas, independente da liberação de produtos de ciclo-oxigenase, assim como apresenta importante atividade coagulante. / Abstract: Crotoxin, the main toxic component isolated from the venom of the South American rattlesnake Crotalus durissus terrificus, is a reversible protein complex composed of a non-toxic non-enzymatic acid peptide (crotapotin) and a toxic basic phospholipase A2 (PLA2). Since several venom proteins interfere in blood coagulation and platelet aggregation, the objective of this study was to evaluate whether crotoxin induces human washed platelet aggregation. Crotoxin was isolated by gel filtration of the crude venom on a Sephadex G-75 column eluted with ammonium bicarbonate buffer (0.1 M, pH 8.0). Human washed platelet aggregation was monitored in a Payton aggregometer and thromboxane release by direct RIA. Fractionation of 100 mg of Crotalus durissus terrificus venom yielded three main peaks,of which the second contained crotoxin. The purity of crotoxin was confirmed by high pressure liquid chromatography analysis on a C 18 µ Bondapack column. Crotoxin (15-50 µg/ml) produced dose-dependent and irreversible human washed platelet aggregation, which was inhibited by pre-incubation of the platelets with SNP (500 µM) or iloprost (100 nM) .Crotoxin also induced TXB2 release (207 ± 8 ng/ml, n=6), it did not inhibit crotoxin-induced aggrega!ion. Our results clearly demonstrate that crotoxin induces human washed platelet aggregation. Although previous reports state that crotoxin does not induce platelet aggregation, we presume that the difference observed is due to the procedure we have used (ammonium bicarbonate buffer instead of formate buffer) to elute crotoxin. / Mestrado / Mestre em Farmacologia

Orientador: Nilce Correa Meirelles / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-07-20T00:10:31Z (GMT). No. of bitstreams: 1 Malheiros_SoniaValeriaPinheiro_M.pdf: 2861416 bytes, checksum: de7c425fc1049e8d786b3ab7fff79dfd (MD5) Previous issue date: 1995 / Resumo: As drogas fenotiazínicas são amplamente utilizadas como neurolépticos e antipsicóticos. A trifluoperazina (TFP), um derivado fenotiazínico, dependendo da concentração, pode induzir hemólise ou proteger eritrócitos da lise em condição isosmótica. Nesse trabalho verificamos a interferência do sistema microssomal hepático (SMH), que é o principal responsável pela biotransformação de drogas nos organismos vivos, no efeito hemolítico causado pela TFP. O efeito hemolítico da TFP é abolido em presença de microssomas de fígado de rato (SMH), o que se deve em parte à biotransformação dirigida pelas enzimas P-450 microssomais e em parte à partição da droga na membrana microssomal, diminuindo a concentração livre da droga. Foi detectado um sobrenadante pós-microssomal (SPM) que mantinha a mesma característica de proteção hemolítica apresentada pelo SMH. Para essa fração solúvel (SPM) de composição proteica 48% e ribonucleica 24 % foi feita uma caracterização bioquímica, constituída basicamente de: determinação do pH, condutividade, caracterização dos espectros de absorção óptica e de ressonância magnética nuclear de prótons (lH-RMN), além da análise cromatográfica por HPLC e determinação da massa molecular aparente por eletroforese. Para todas as nove frações de SPM obtidas na separação cromatográfica, cujos pesos moleculares aparentes variam de 12 a 160 kDa, foi observada proteção tanto contra hemólise induzi da pela TFP quanto contra a hemólise mecânica / Abstract: Phenothiazine drugs are mainly used as neuroleptics and antipsychotic agents. Trifluoperazine (TFP), a phenothiazine derivative, produces either hemolysis or protection of erythrocytes under isosmotic conditions in a dose-dependent manner. In these work we verify the interference of mouse liver microsomes (MLM), which are the main responsible for drug biotransformation in organisms, in the hemolytic effect caused by TFP. The hemolytic effect induced by TFP is abolished in the presence of MLM which is due, in part, to microsomal cytochrome P-450 driven biotransformation and a TFP partition into the microsomal membrane that decreases the free concentration of the drug. A post microsomal supematant (PMS) composed of proteins (48 %) and ribonucleic acid (24 %) has been found to exhibit the same protection against hemolysis as MLM. In this work, we showed the PMS biochemical characterization that consisted of: pH and conductivity determination, optical and nuclear magnetic resonance (NMR) spectroscopy, besides cromatographyc and electrophoretic analysis. The nine fractions obtained from PMS by cromatographic separation, which molecular weight was between 12 and 160 kDa, protected erythrocytes against mechanical and TFP induced hemolysis / Mestrado / Bioquimica / Mestre em Ciências Biológicas

The extracellular loops of muscarinic acetylcholine receptors are predicted to play a role in the binding and regulation of allosteric modulators. Furthermore, the sequence of the five subtypes of muscarinic receptors shows a large degree of diversity in this region. M3 receptor mutants, K523E, D518K and N132G, in which the substituted residues were those corresponding to the M1 subtype, were studied. As the amino acids in positions 518 and 523 are charged, the uncharged mutants, K523Q and D518N, were also created in order to observe any possible effect of charge. One question examined is whether these mutations changed the binding of orthosteric and allosteric ligands, generating a M1 receptor phenotype.Radioligand binding experiments revealed that one mutant, K523E, had a profound potentiating effect on the binding of prototypical modulators like gallamine, strychnine, brucine and N-chloromethylbrucine, but had minimal effects on the binding of a number of orthosteric ligands, including [3H]N-methylscopolamine ([3H]NMS) and acetylcholine (ACh). The increase in affinity was found at both the unoccupied and [3H]NMS-occupied receptors, with up to 70 fold increases in affinity being observed. Switches from negative to positive cooperativity for some strychnine-related compounds were found.At K523E, the affinities of the strychnine-related ligands were also increased up to 160 fold at the receptor-ACh complex, with up to 35 fold positive cooperativity being observed. Positive cooperativity of this magnitude is the highest that has been reported for M3 receptors.The dramatic changes in cooperativities and affinities of allosteric ligands at K523E did not result in generation of the M1 phenotype. The K523Q data suggest that the large changes in K523E result from the introduction of the negatively charged glutamate residue and not the loss of the positively charged lysine. The effect of K523E seems to be solely on the binding of allosteric ligands and the transmission of the effects of their binding to the orthosteric site.For the ligands acting at the gallamine site, all the effects of the allosteric modulators on ACh binding have been reproduced in functional studies, indicating that the allosteric modulation, seen in binding, is transmitted to the cellular response. A novel and unexpected finding is that WIN62,577 is an allosteric agonist at M3 muscarinic receptors and at K523E and N132G. The study also revealed that nanomolar concentrations of ACh may be present in assays of muscarinic receptor function and may give misleading interpretations of data. These artefacts were removed by preincubation with acetylcholinesterase, a control not previously used in functional studies of muscarinic receptors.The sensitivity of the binding of both orthosteric and allosteric ligands to the composition of the binding assay buffer has also been investigated in detail. In a phosphate buffer of low ionic strength (PB) the affinity constants of all the compounds studied, both orthosteric and allosteric, were increased, relative to a Hepes buffer of higher ionic strength, except for WIN 62,577, an allosteric ligand which binds to a different allosteric site from the prototypical modulators, and SVT-40776 a new M3 selective antagonist, indicating their different modes of binding. Cooperativities have also been switched from negative to positive by changing buffer.The two factors affecting the allosteric binding parameters of M3 receptors, PB and the mutation K523E, mutually potentiate each others effects. We have been able to obtain up to 10,000 fold changes in the affinity at the unoccupied receptor and 6400 fold increases in affinity at the ACh occupied receptor.The possible location of K523, relative to other residues on the external loops of muscarinic receptors shown to be important for the binding of allosteric ligands, has been explored using different models based on the X-ray structures of rhodopsin and the â2 adrenergic receptor.