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Efecto de recomendaciones de uso en la utilización de ceftriaxona y quinolonasÁvila Oesterle, Fernanda January 2015 (has links)
Residencia para optar al Título de Profesional
Especialista en Farmacia Clínica y Atención Farmacéutica / Fundamentación: Actualmente cerca de la mitad de las prescripciones de antibióticos son inadecuadas, lo que aumenta la presión selectiva y la resistencia bacteriana. Cefalosporinas y fluoroquinolonas son familias de antibióticos ampliamente relacionadas con este fenómeno: Se han asociado con un aumento de las bacterias productoras de β-lactamasas y son un factor de riesgo para infecciones por Clostridium difficile, por lo que las agencias reguladoras proponen intervenciones que busquen racionalizar su uso.
Objetivo:Evaluar el efecto de recomendaciones de uso en la proporción de prescripciones inadecuadas de ceftriaxona y fluoroquinolonas.
Metodología: Se desarrolló en un hospital universitario, un estudio de antes y después, prospectivo e intervencional, que consistió en el diseño y difusión de recomendaciones de uso para los tratamientos empíricos de enfermedades infecciosas adquiridas en la comunidad. Se comparó la calidad y la cantidad de uso de ceftriaxona y FQ antes y después de la intervención. Los outcomes medidos fueron la proporción de prescripciones inadecuadas y las dosis diarias definidas. Se analizaron los datos por medio de pruebas estadísticas como el Test de Chi cuadrado, corrección de Fisher y Test de Student.
Resultados: Se midió el impacto de las recomendaciones de uso en una muestra de 206 pacientes hospitalizados con diagnósticos de enfermedades infecciosas adquiridas en la comunidad.Con la implementación de las recomendaciones de uso se logró disminuir en un 35% las prescripciones inadecuadas de antibióticos, siendo el efecto más visible en lo referente a la indicación y duración de las terapias. Se observó una disminución del consumo de ceftriaxona y levofloxacino y un aumento significativo de la utilización de ampicilina/sulbactam.
Conclusiones:La implementación de recomendaciones de uso basadas en la evidencia científica disponible y en la susceptibilidad bacteriana local, permitió disminuir la proporción de prescripciones inadecuadas y reducir el consumo de ceftriaxona y fluoroquinolonas, en un hospital universitario de alta complejidad / Background: Nowadays near to the half of antibiotic prescriptions are inadequate, which leads to an increase of the selective pressure and antibiotic resistance. Cephalosporins and fluoroquinolones are two families of antibiotics closely related with this phenomenon: their use has been associated with an increase of β-lactamase-producing-bacteria and also represent a risk factor to Clostridium difficile infection, for this reason the regulatory agencies are constantly proposing interventions in order to rationalize the use.
Objective: To assess the impact of the therapeutic use recommendation of ceftriaxone and fluoroquinolones in the inadequate prescription ratio.
Methodology:This project was developed in a Universitary Hospital, based in a prospective and interventional studio, which included the design and diffusion of therapeutic use recommendations for the empiric treatment of infectious diseases acquired in the community. The quality of use and consumption of ceftriaxone and FQ, before and after the intervention, were compared.The outcomes were measure according to the proportion of inadequate prescriptions and the defined daily dose and the database were analyzed using statistical tests, such a, Chi Square Test, Fisher Correction and Student Test. Results:The impact of therapeutic use recommendations was measure in 206 hospitalized patients with the following diagnostic: infectious diseases acquired in the community. As a result of the implementation of these recommendations, the inadequate antibiotic prescription was decreased in a 35%, being the indication and duration of therapy the most observable effect. Regarding to the amount of drugs used a decrease of the ceftriaxone and levofloxacin consumption and increase in the ampicillin/sulbactam use was observed.
Conclusions: The implementation of therapeutic use recommendations based on the available scientific evidence and the local bacterial susceptibility allows todecrease the inadequate prescription ratio and reduces the consumption of antibiotics in a High Complexity Universitary Hospital
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Estudos de Novas Metodologias Sintéticas para Heterocíclicos Quinolônicos, Triazólicos e Síntese de Catalisadores QuiraisThatyana Rocha Alves 29 March 2004 (has links)
In order to obtain quinolone nucleosides a new methodology based on construction of the heterocyclic ring at the carbohydrate moiety was devised. The carbohydrates: 1-methoxy-2,3-O-isopropylidene-α-D-ribofuranose (108), 1-methoxy-2,3-O-isopropylidene-5-O-methanesulfonyl-β-D-ribofuranose (109a) and 1-methoxy-2,3-O-isopropylidene-5-O-p-toluenesulfonyl-β-D-ribofuranose (109b) were prepared. The last two, the mesyl and tosyl derivatives, were submitted to nucleopilic substitution reaction with aniline or its corresponding anion, leading to 1-methoxy-2,3-O-isopropylidene-5-anilino-β-D-ribofuranose (110) in very low yield. Attempts to improve this yield by changing reaction conditions such as the polarity of the solvent or nitrogen eletronic density were unsuccessful. It seems that the elimination process is the most favorable under these conditions in the ribofuranoside ring.Also, the aldehyde 126 was prepared in order to produce 110 throught reductive amination reaction. Although, this synthesis has failed. Reaction of the amine 110 with diethyl ethoxymethylene malonate didn`t lead to ethyl N-phenyl-2,3-O-isopropilydene-ribofuranoside-α-carbethoxy-β-(anilino)acrylate (111), probably due to steric effects around the nitrogen. In the search for obtaining new quinolonic 2’,3’-didehydro-ribonucleosides (type II), several intermediates were prepared by using a methodology optimized in our group, which involves coupling previous sylilated 3-carbetoxy-4(1H)quinolones (X= F, 116a and X = Me, 116b) by reaction with N,O-bis(trimethylsilyl)trifluoracetamide (BSTFA), with 1-O-acetyl-2’,3’,5’,-tri-O-benzoyl-β-D-ribofuranose (23),under trimethylsilyltrifluormethanesulfonate (TMSO-Tf) catalysis. 3-Carbethoxy-1-(2’,3’,5’,-tri-O-benzoyl-β-D-ribofuranosyl)-4(1H)quinolone 117a-b were obtained in 83 and 85% yields, respectively. The acrylates 115a-b used to prepare the corresponding quinolones 116a-b were synthesized in 85 and 75% yields by a procedure described in the literature. The benzoyl protecting groups of the ribonucleosides 117a-b were removed by using methanolic sodium carbonate solution leading to the unprotected 3-carbomethoxy-1-β-D-ribofuranosyl-4(1H)quinolones 118a-b in 75% and 69% yields. These ribonucleosides were submitted to bromination and acetylation. Ribonucleoside 118b formed a 3:1 mixture of 2`-O-acety-3`-bromo and 3`-O-acety-2`-bromo regioisomeric derivatives. However, the same reaction with 118a produced the 2’,3’,5’-tri-O-acetylated derivative. Attempts to perform β-elimination reaction of the bromo-acetate ribonucleoside 118b to obtain the desired didehydro-nucleosides, using as reagent nickel deposited on charcoal surface were unsuccessful.Continuing our search for new heterocyclic nucleosides was investigated the preparation of triazolic derivatives (type III). The synthetic route devised started by preparing the aminocarbohydrates 129, 147, 150, 156 and 156, by a standard procedure described in the literature. These amino derivatives were reacted with diazomalonaldehyde (132) and diazoacetylacetone (133) affording 4-formyl-1,2,3-triazole-1-yl (130a e 148a) and 4-acetyl-5-methyl-1,2,3-triazole-1-yl (130b, 148b and 152a). The triazolic nucleoside 130a was tested against Herpes simplex virus type 1 (HSV-1) showing a good inhibition of the virus (86%) at the concentration 50 M. Biological evaluation of this substance against HIV-1 virus is under study. All the nucleosides synthesized are also being tested against HSV-1 and HIV-1 virus.
As an extension of our study on carbohydrate derivatives we undertook a search for new chiral Lewis acids based on stannylated carbohydrates. With this purpose we planned the preparation of the chiral Lewis acids 157a, 158a e 163a. Three reactions between tosylated carbohydrates 109b, 121 and 145 and Ph3SnLi were attempted. However, only carbohydrate 109b led to 1-methoxy-2,3-O-isopropylidene-5C-triphenylstannyl-α-D-ribofuranose (157a). In contrast, the reaction of Ph3SnLi with 121 produced 4,5-anhydro-1,2-O-isopropylidene-α-D-xylofuranose, rather than the stannylated substitution product. The carbohydrate 145 failed to produced any desired product. Thus it appears, superficially at least, that Ph3SnLi is acting as a nucleophille with 109b and as a base towards 121, eliminating p-MeC6H4SO3H. The lack of reactivity of 145 results from the steric hindrance by 3-sulfonate group difficulting the approach of the bulky tin-lithium reagent in an SN2-type reaction. Reactions of 157a with iodine, at both 1:1 and 1:2 mole ratios of 157a:I2, proceeded at ambient
temperature to give the iodophenylstannylated products, 157b and 157c, in good yields. The chiral Lewis acids 157a-c were used in Diels-Alder reactions between methyl acrylate (122) and cyclopentadiene (123). The aduct 124 which was formed in the presence of 157c had its optical rotations measured. Chiral Lewis acid 157c was able to induce chirality leading to S configuration adduct as the major enantiomer (91% of enantiomeric excess). During the study on Diels-Alder reaction we had the opportunity to get a chiral catalyst, the fluoro-bis-oxazolidine 164 synthesized by Prof. Denis Sinou of Université Claude Bernard-Lyon I. We prepared in situ a copper complex of this compound and it was used in the Diels-Alder reaction between methyl acrylate (122) and cyclopentadiene (123). The result indicated that this catalyst was able to induce chirality in the cycloaduct favoring the S enantiomer (87% of enantiomeric excess).
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Detecção e caracterização de determinantes de resistência aos antibióticos ß-lactâmicos e quinolonas em bactérias Gram-negativas isoladas de amostras clínicasVIANA, André Luiz Machado 14 February 2012 (has links)
O presente trabalho teve como principal objetivo a detecção e caracterização dos genes plasmideais de resistência às quinolonas qnr, aac(6’)-Ib-cr e qepA, , e ainda, os genes blaTEM, blaSHV e blaCTX-M, codificadores de -lactamases de espectro estendido (ESBL) em coleções de enterobactérias isoladas a partir de amostras clínicas obtidas em dois hospitais do estado de Minas Gerais. No período de junho a outubro de 2010, foram isoladas 873 enterobactérias das quais 106 (12%) foram triadas para este estudo por apresentarem diminuição de sensibilidade ao ácido nalidíxico. A identificação bacteriana foi realizada através de testes bioquímicos convencionais e pelo sistema automatizado MicroScan - autoSCAN®-4. O perfil de sensibilidade aos antimicrobianos foi determinado pelo método de disco difusão e a concentração inibitória mínima foi determinada por microdiluição em caldo, como descrito e recomendado pelo “Clinical Laboratory Standards Institute - CLSI”, para os isolados produtores do gene qnr e seus respectivos transconjugantes. A detecção dos genes associados aos mecanismos de resistência estudados e a análise das mutações presentes nos genes cromossômicos gyrA e parC foram realizadas por PCR e sequenciamento. A extração de plasmídeos das bactérias e seus transconjugantes, contendo os determinantes qnr, foi realizada segundo a técnica de Kieser. Os resultados obtidos pela eletroforese em campo pulsado foram interpretados segundo os critérios estabelecidos por Tenover et al., 1995. A coleção bacteriana foi composta por: Escherichia coli (n=61; 57,6%), Enterobacter cloacae (n=23; 21,7%), Klebsiella pneumoniae (n=16; 15,1%), Proteus mirabilis (n=3; 2,8%), Serratia marcescens (n=2; 1,9%) e Proteus vulgaris (n=1; 0,9%). A maioria das enterobactérias (82%) foi isolada de infecções do trato urinário seguido de hemoculturas, swab de secreções, aspirado traqueal e ponta de cateter. De acordo com os critérios do CLSI, 94% (n=100) das enterobactérias foram resistentes ao ácido nalidíxico, 71% (n=75) foram resistentes à ciprofloxacina e 76% (n=81) apresentaram diminuição de sensibilidade a ceftazidima e/ou cefotaxima. A pesquisa de qnr resultou na detecção dos genes qnrB e qnrS em treze isolados, incluindo E. cloacae (n=6), K. pneumoniae (n=5) e E. coli (n=2). O gene qnrB1 foi o mais prevalente, seguido de qnrS1, qnrB2 e qnrB19. Nas amostras qnr positivas, foram detectados 4 isolados positivos para o gene aac(6’)-Ib-cr, 6 isolados para blaSHV, 11 isolados para blaCTX-M e 11 isolados para o gene blaTEM. O determinante qepA não foi detectado. Este trabalho indica a disseminação de mecanismos de resistência às quinolonas mediados por plasmídeos (PMQR) em amostras clínicas no Brasil. A coexistência de genes ESBL e PMQR demonstra a complexidade dos plasmídeos carreando determinantes de resistência entre os membros da família Enterobacteriaceae. / The main objective of this work was to characterize the qnr, aac(6')-Ib-cr and qepA plasmid genes, and also the blaTEM, blaSHV and blaCTX-M genes, encoding for extended spectrum β-lactamases - ESBL in a collection of Enterobacteriacecae isolated from clinical samples obtained in two hospitals in the state of Minas Gerais, Brazil. A total of 873 Enterobacteriaceae were isolated in the period of June to October 2010 of which 106 (12%) were screened for this study showing decreased susceptibility to nalidixic acid. The bacterial identification was performed by conventional biochemical tests and by the automated system MicroScan autoSCAN®-4. The antimicrobial susceptibility profile was determined by diffusion disk and the minimum inhibitory concentration was determined by broth microdilution for the isolates carrying the qnr genes e their respective transconjugantsaccording with the recommendations of the "Clinical Laboratory Standards Institute - CLSI". PCR and sequencing were performed to detect plasmid-mediated quinolone resistant (PMQR) genes as well as the analysis of mutations in chromosomal encoded genes, gyrA and parC by. The extraction of plasmids and their transconjugants containing qnr determinants was performed using the technique of Kieser. The results obtained by pulsed field gel electrophoresis were interpreted according with Tenover et al., 1995. The collection was composed as follow: Escherichia coli (n = 61, 57.6%), Enterobacter cloacae (n = 23, 21.7%), Klebsiella pneumoniae (n = 16, 15.1%), Proteus mirabilis (n= 3, 2.8%), Serratia marcescens (n = 2, 1.9%) and Proteus vulgaris (n = 1, 0.9%). Most of the enterobacteria (82%) was isolated from urinare followed by blood, swab of secretions, tracheal aspirate and catheter tip. A total of 100 (94%) isolates were resistant to nalidixic acid, 75 (71%) were resistant to ciprofloxacin and 81 (76%) showed reduced susceptibility to ceftazidime and/or cefotaxime. The qnr plasmidic determinant research resulted in the detection of qnrB and qnrS genes in 13 isolates, including E. cloacae (n=6), K. pneumoniae (n=5) andE. coli (n=2). QnrB1 was the most prevalent gene, followed by qnrS1, qnrB2 and qnrB19. In four qnr positive isolates also carried the aac(6')-Ib-cr gene, to blaSHV-like (n=6), blaCTX-M (n=11) and blaTEM gene (n=11). The qepA gene was not detected. This work indicates the dissemination of PMQR in clinical specimens in Brazil. The coexistence of ESBL and PMQR genes demonstrate the complexity of plasmids carrying resistant genesamong members of the family Enterobacteriaceae.
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Síntese e fitotoxicidade de 3-arilquinolin-4(1H)-onas / Synthesis and phytotoxic activity evaluation of 3-arilquinolin-4(1H)-onesMiranda, Izabel Luzia 23 February 2015 (has links)
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Previous issue date: 2015-02-23 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / As quinolonas constituem uma classe de compostos que apresentam diversas atividades biológicas como medicinais, farmacêuticas e agroquímicas. Apresentam ainda, atividade sobre o fotossistema II, inibindo a cadeia transportadora de elétrons, o que confere a esta classe de compostos uma potencial atividade herbicida. Sua principal fonte natural é constituída por plantas da família Rutaceae. O presente trabalho objetivou a síntese de novas 3-arilquinolin-4(1H)-onas, partindo-se de uma etapa de ciclocondensação entre a 2- aminoacetofenona e o formato de metila que forneceu a quionolin-4(1H)-ona com 84% de rendimento. A segunda etapa consistiu numa reação de iodação, para adição de um bom grupo abandonador à molécula, e se processou com 92% de rendimento. Em seguida o grupo NH da quinolona foi protegido por meio de uma reação de metilação (88%). Por fim a 3-iodo-1- metilquinolin-4(1H)-ona foi submetida a uma reação de acoplamento de Suzuki-Miyaura fornecendo doze análogos: 1-metil-3-fenilquinolin-4(1H)-ona (64%), 3-(2-metoxifenil)-1- metilquinolin-4(1H)-ona (78%), 3-(4-fluoro-2-metoxifenil)-1-metilquinolin-4(1H)-ona (68%), 3-(5-fluoro-2-metoxifenil)-1-metilquinolin-4(1H)-ona (77%), 3-(5-bromo-2-metoxifenil)-1- metilquinolin-4(1H)-ona (65%), 3-(5-cloro-2-metoxifenil)-1-metilquinolin-4(1H)-ona (70%), 3-(3-clorofenil)-1-metilquinolin-4(1H)-ona (73%), 3-(4-clorofenil)-1-metilquinolin-4(1H)-ona (75%), 3-(4-bromofenil)-1-metilquinolin-4(1H)-ona (65%), 3-(3-metoxifenil)-1- metilquinolin-4(1H)-ona (71%), 3-(3-bromofenil)-1-metilquinolin-4(1H)-ona (61%) e 3-(4- metoxifenil)-1-metilquinolin-4(1H)-ona (72%). A avaliação de atividade fitotóxica foi realizada por meio de ensaio em placa de Petri empregando-se sementes de sorgo (Sorghum bicolor) e de pepino (Cucumis sativus) como indicadores de fitotoxicidade e por meio de ensaio in vitro de inibição do transporte de elétrons em cloroplastos de espinafre (Spinacea oleracea L.). De forma geral, os compostos apresentaram maior fitotoxicidade para a espécie dicotiledônea (pepino). O composto 25 foi o mais seletivo. No ensaio de inibição da reação de Hill, o composto 21 foi o que apresentou maior efeito sobre a redução do ferricianeto de potássio na presença de cloroplastos isolados de folhas de espinafre nas concentrações de 50 e 100 μM. / The quinolones are a class of compounds which exhibit various biological activities such as medical, pharmaceutical and agrochemical. Still present activity on the photosystem II, inhibiting electron transport chain, which gives this class of compounds a potential herbicide activity. Its main natural source consists of plants of Rutaceae family. And mostly commercially available quinolones are of synthetic origin. This study aimed to the synthesis of new 3-arilquinolin-4-(1H)-ones, starting from a cyclocondensation step between the 2- methyl aminoacetofenone and the methyl formate that provided the quionolin-4-(1H)-one with 84% yield. The second stage consisted of an iodination reaction in addition to a good leaving group molecule, and processed in 92% yield. Next, the NH group of the quinolone is protected by means of a methylation reaction (88%). Finally, the 3-iodo-1-methyl-quinolin-4 (1H)-one was subjected to a coupling reaction of Suzuki-Miyaura providing twelve analogues: 1-methyl-3-phenylquinolin-4 (1H) -one (64%) 3- (2-methoxyphenyl) -1-methyl- quinolin-4 (1H) -one (78%), 3- (4-fluoro-2-methoxyphenyl) -1-methyl-quinolin-4 (1H) -one (68 %) 3- (5-fluoro-2-methoxyphenyl) -1-methyl-quinolin-4 (1H) -one (77%) 3- (5-bromo-2- methoxyphenyl) -1-methyl-quinolin-4 (1H) -one (65%) 3- (5-chloro-2-methoxyphenyl) -1- methyl-quinolin-4 (1H) -one (70%) 3- (3-chlorophenyl) -1-methyl-quinolin-4 (1H) -one (73%) 3- (4-chlorophenyl) -1-methyl-quinolin-4 (1H) -one (75%) 3- (4-bromophenyl) -1- methyl-quinolin-4 (1H) -one (65%) 3- (3-methoxyphenyl) -1-methyl-quinolin-4 (1H) -one (71%) 3- (3-bromophenyl) -1-methyl-quinolin-4 (1H) -one (61%) and 3 - (4-methoxyphenyl) -1-methyl-quinolin-4 (1H) -one (72%). Assessment of phytotoxicity was carried out by means of the Petri dish assay employing seeds of sorghum (Sorghum bicolor) and cucumber (Cucumis sativus) as indicators and phytotoxicity by testing inhibition of electron transport in spinach chloroplasts (Spinacea oleracea L.) in vitro. In general, the compounds showed higher phytotoxicity for dicot species (cucumber). Compound 25 was the most selective. With respect to inhibition assay Hill reaction compound 21 showed the highest effect on the reduction of potassium ferricyanide in the presence of chloroplasts isolated from spinach leaves at concentrations of 50 and 100 μM, respectively.
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Impactos do tratamento antimicrobiano no cérebro fetal devido a peritonite autógena fecal em ratas / Impacto do tratamento antimicrobiano no cérebro fetal devido a peritonite autógena fecal em ratas Wistar: estudo histomorfométricoGADELHA, Neylane Nyeria Coelho Batista 24 February 2016 (has links)
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Previous issue date: 2016-02-24 / Objetivo: Investigar a densidade neuronal do cérebro de ratos recém-nascidos cujas
mães foram submetidas a peritonite autógena fecal e comparar com aqueles cuja mãe
recebeu tratamento antimicrobiano agressivo. Métodos: Duas ratas prenhas se
submeteram a peritonite com suspensão a 10% de fezes, na dose de 4 ml por
quilograma, tendo uma recebido tratamento antimicrobiano venoso constituído por
injeção de moxifloxacino na dose de 15 mg/kg e dexametasona na dose de 2,5 mg/kg
(contidos em colírio de cloridrato de moxifloxacino a 0,5% e fosfato de dexametasona
a 0,1%, além de dois mililitros de extrato alcoólico/aquoso da entrecasca de Schinus
terebinthifolius raddi que foi injetada na cavidade abdominal. Ambos agentes
antimicrobianos foram feitos 24 h após a indução da peritonite. Uma rata prenha não
foi submetida a peritonite, nem intervenções, sendo caracterizada como grupo
controle. Resultados: Os cérebros dos ratos recém-nascidos cujas mães receberam 4
ml/kg da suspensão de fezes a 10% evidenciaram menor tamanho e consistência mais
amolecida do que aqueles das mães que tinham recebido tratamento antimicrobiano
e os normais do grupo controle. A densidade neuronal do cérebro dos conceptos de
mães não tratadas foi significantemente diminuída quando comparada com os grupos
tratada e controle p < 0,01. Conclusão: Peritonite não tratada em ratas prenhas pode
produzir dano cerebral nos conceptos. Tratamento efetivo precoce pode prevenir a
diminuição da densidade neuronal do cérebro. A translação para humanos é que a
infecção intra-abdominal em mulheres grávidas pode estar associada a dano cerebral
nos conceptos. Isto pode ser prevenido usando abordagem terapêutica precoce e
adequada. / Purpose: To investigate the neuronal density of newborn rat brain whose mothers were
subjected to autogenously fecal peritonitis and compare with those whose mothers
received aggressive antimicrobial treatment. Methods: Two pregnant rats underwent
peritonitis with a 10% suspension of feces at a dose of 4 ml per kilogram. One of them
received intravenous antimicrobial treatment consisting of a combination of
moxifloxacin at a doses of 15 mg/kg and dexamethasone at a doses of 2.5 mg/kg as
an eye drop solution (moxifloxacin cloridrat 0,5% and dexamethasone phosphate
0.1%), in addition of two milliliters of alcohol/aqueous extract of the inner bark of
Schinus terebinthifolius raddi which was injected into the abdominal cavity. Both
antimicrobial agents were injected 24 h after the induction of peritonitis. One pregnant
rat didn’t receive peritonitis or treatment. It was reported as control group. Results: The
brains of newborn rats whose mothers were given 4 ml / kg of 10% fecal suspension
evidenced smaller and softer consistency than those from mothers that had received
antimicrobial therapy and normal control group. The neuronal density in the brains of
untreated fetuses mothers was significantly reduced when compared with the control
and treated groups p <0.01. Conclusion: Peritonitis untreated in pregnant rats can
produce brain damage. Early effective treatment can prevent the decrease of neuronal
densities in the brain. The translation to human is the intra-abdominal infection in
pregnant women may be associated with brain damage in her concepts. This can be
prevented by using early and appropriate therapeutic approach.
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Validación de un método analítico para la detección de flumequina y ácido oxolínico en tejidos comestibles de pollos BroilerPérez Bello, Bárbara Alejandra January 2008 (has links)
Memoria para optar al Título Profesional de Médico Veterinario / Las quinolonas y fluoroquinolonas corresponden a un grupo de drogas antibacterianas que han sido ampliamente utilizadas en medicina veterinaria. Particularmente, durante la última década, el uso de estos fármacos ha sido explosivo en producción animal, con el consecuente riesgo de generar residuos de estos fármacos en productos destinados a consumo humano. Con el objetivo de entregar a los consumidores un producto inocuo libre de residuos peligrosos para la salud, se han establecido límites máximos residuales (LMR) por parte de varios países como Japón y Chile y organizaciones internacionales, como la Food and Drug Administration (FDA) y la Unión Europea. El control necesario para que los productos de origen pecuario cumplan con los LMR se realiza dentro de Programas de Control de Residuos. Dichos programas deben contar con metodologías analíticas validadas.
En este contexto, el objetivo de este trabajo fue validar un método analítico confirmatorio para la detección de residuos de ácido oxolínico y flumequina en músculo de pollos broiler, mediante el empleo de Cromatografía Líquida con Detector de Masa (LC-Ms/Ms) de acuerdo a las normativas de la Comunidad Europea y la de Estados Unidos de América, de manera que pueda ser utilizado en el Programa Nacional de Control de Residuos de Productos de Exportación.
Para validar el método fue necesario fortificar muestras de músculo de pollos broiler libres de antimicrobianos con distintas concentraciones de ácido oxolínico y flumequina y analizarlas utilizando Cromatografía Líquida acoplado a un Detector Masa-Masa (LC-Ms/Ms). La sensibilidad del método determinó un límite de detección o CC de 0,72 µg/kg para ácido oxolínico y 0,53 µg/kg para flumequina. Se obtuvo un límite de cuantificación o CC de 1,21 µg/kg para ácido oxolínico y 1,54 µg/kg para flumequina. El coeficiente de correlación para los analitos fue mayor a 0,9 (R>0,9).
De acuerdo a los resultados obtenidos, el método cumple con las condiciones de validación establecidas por la Decisión 2002/657/CE, en relación a los parámetros de linealidad, sensibilidad y repetitividad. En el caso de la recuperación, debido a que este parámetro arrojó valores no aceptados por la norma (Unión Europea, 2002), éste debe ser reevaluado previo al análisis de muestras para la detección de residuos de ácido oxolínico y flumequina en músculo de pollo en caso que éste sea utilizado en un Programa de Control de Residuos. / Quinolones and fluoroquinolones are a group of antibacterial drugs that has been widely used in veterinary medicine. During the last 10 years, these drugs have had an explosive use in food producing animals, wich may cause drug residues in products for human consumption. To assure the delivery of safe products to consumers, maximum residual limits (MRLs) have been established by countries such as Japan and Chile and different organizations, such as the Food and Drug Administration (FDA) and the European Union. Control Programs of Drug Residues are required in order that products from animal origin fulfill the MRLs. These programs must operate with adequately validated analytical methodologies.
In this context, the objective of this work was to validate a confirmatory analytical method for the detection of oxolinic acid and flumequine in muscle of chickens, by means of the use of Liquid Chromatography-Tandem Mass Spectrometry (LC-Ms/Ms) according to the European Community and the United States of America requirements, so that it can be used in the National Control Program of Residues of animal products that will be exported to other countries.
To validate the analitical method, free-drug muscle samples collected from broiler chickens analysis were needed. Samples were spiked with different concentrations of oxolinic acid and flumequine and analized using LC-Ms/Ms.
The sensitivity of the method expressed as detection limit (CC) was 0.72 µg/kg for oxolinic acid and 0.53 µg/kg for flumequine. The detection capability (CCβ) was 1.21 µg/kg for oxolinic acid and 1.54 µg/kg for flumequine. The coefficient of correlation for the analytes was higher than 0.9 (R>0.9).
According to these results, the method fulfills the conditions of validation established by Decision 2002/657/CE, in relation to parameters of linearity, sensitivity and repeatability. In the case of the recovery, this parameter threw unacceptable values compared with the established in european regulations (European Community, 2002), and must be again assessed previous to the analysis of samples for oxolinic acid and flumequine residues in a Control Programs of Residues.
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Estudio de los mecanismos de mutagénesis y potencia mutagénica de quinolonasGonzález Cabeza, José Guillermo 08 October 2004 (has links)
Dada la importancia clínica de las quinolonas en el control de enfermedades infecciosas y las posibles implicaciones que puede tener el hecho de que estas moléculas sean agentes mutagénicos en bacterias, el presente estudio se ha centrado en profundizar en los mecanismos de mutagénesis, utilizando la ciprofloxacina como molécula modelo, y en determinar el potencial mutagénico de quinolonas de actual uso clínico.En lo que se refiere a los mecanismos de mutagénesis, se ha demostrado que para la mutagénesis inducida por ciprofloxacina, se requiere que las bacterias posean un sistema de reparación de escisión de nucleótidos (NER) funcional, descartándose que el operón moa, el cual codifica genes de biosíntesis de cofactores de molibdeno tenga algún papel en dicha mutagénesis.Estos resultados corroboran estudios anteriores, los cuales sugerían la participación del sistema NER en dicha mutagénesis, e indican que probablemente otros genes deleccionados en las cepas de ensayo de S. enterica Typhimurium TA104 y TA2659 distintos del uvrB, no deben tener un papel importante en la mutagénesis mediada por las quinolonas.Por otra parte, se ha demostrado que la ciprofloxacina puede generar alguna especie reactiva de oxígeno, probablemente el anión superóxido (O2-) y/o oxígeno singlete produciendo daño oxidativo, el cual no debe de ser preferentemente la lesión 8-oxoG.El conjunto de estos resultados indica que las quinolonas deben de producir diferentes tipos de lesiones en el DNA de las células bacterianas. Así, la interacción de la molécula de quinolona con el complejo DNA - DNA girasa debe generar un tipo de distorsión análoga a un enlace intercatenario, dando lugar a una lesión premutagénica. Dicha lesión puede ser procesada por el sistema NER y convertirse en una lesión mutagénica sobre la cual actuaría una DNA polimerasa tendente al error, análoga a MucAB y que introduciría una mutación. Este mecanismo de mutagénesis debe ser común a este tipo de moléculas. Por otra parte, los resultados obtenidos en mutantes soxRS indican que esta familia de compuestos también introducen lesiones oxidativas, las cuales deben de ser más relevantes en aquellas moléculas descritas como fototóxicas, como clinafloxacina, lomefloxacina y otras.Finalmente, y utilizando ensayos de retromutación en E. coli y S. enterica Typhimurium, se ha demostrado que las quinolonas de cuarta generación clinafloxacina, trovafloxacina y gemifloxacina son las que presentan mayor actividad mutagénica, mientras que levofloxacina y moxifloxacina son las que producen un menor número de revertientes en ambos sistemas de ensayo. El potencial mutagénico de cada quinolona debe de estar relacionado con su estructura molecular, permeabilidad de la bacteria y acumulación de las quinolonas. Así, se relaciona la baja capacidad de mutagénesis de la moxifloxacina en ambos ensayos con la presencia de un grupo metoxi en posición C-8, mientras que la ciprofloxacina es detectada como una molécula de elevada capacidad mutagénica en E. coli WP2 / pKM101 y de baja actividad en S. enterica Serov. Typhimurium. Es de señalar que la mutagénesis estudiada se manifiesta a dosis de quinolonas inferiores a la CMI de cada molécula en las cepas de ensayo. En atención a estos resultados se discute las posibles implicaciones de la exposición de las poblaciones de patógenos a bajas dosis de quinolonas y se propone este tipo de estudio como clave para el desarrollo de nuevas moléculas de esta familia de antimicrobianos, los cuales deberían presentar una mejor actividad antibacteriana junto a una baja capacidad de introducir mutaciones. / Given the clinic importance of the quinolones in the control of infectious diseases and their possible involvement in the bacterial mutagenesis, this study has been focused to gain insight into the mutagenesis mechanisms using ciprofloxacin as a model and by determining the mutagenic potential of quinolones in the current clinic administration.In reference to the mutagenic mechanisms, it has been shown that bacteria must own a functional nucleotide excision repair system (NER) for taking part the ciprofloxacin-induced mutagenesis. Furthermore, it has been rule out that moa operon, which codifies genes participating in the biosynthesis of molybdenum cofactors, has a role in such mutagenesis process.These results support early studies which suggested the participation of NER in the above mentioned mutagenesis and indicate that likely other deleted genes apart from uvrB in the tester strains TA104 and TA2659 of Salmonella typhimurium may not have an important role in the quinolones mediated mutagenesisOn the other hand, it has been demonstrated that ciprofloxacin can generate some reactive oxygen species (likely superoxid anion (O2-) and/or singlet oxygen) that produce oxidative damage. This damage may be not preferably the 8-oxoG lesion.All these results together indicate that quinolones have to produce different kinds of DNA lesions in bacterial cells. Thus the interaction of quinolone molecule with the DNA-DNA gyrase complex has to generate a type of distortion analogue to an interchain bond, giving rise to a premutagenic lesion. This lesion can be processed by the NER system and became a mutagenic lesion that could be bypassed by an error-prone DNA polymerase (as MucAB) introducing a mutation. Such mutagenic mechanism has to be common to that kind of molecules. On the other hand, results obtained in soxRS mutants indicate that this family of compounds introduces also oxidative damage which has to be more relevant in phototoxic molecules as clinafloxacin, lomefloxacin, among others.Finally, using retromutation assays in E. coli and S. enterica thyphimurium, it has been demonstrated that fourth-generation quinolones as clinafloxacin, trovafloxacin y gemifloxacin show the highest mutagenic activity, while levofloxacin and moxifloxacin produce a lower number of revertants in both assay systems. The mutagenic potential of each quinolone has to be related to its molecular structure, bacterial permeability and quinolone accumulation. That way the low mutagenic action of moxifloxacin is related to the presence of the metoxy group in C-8 position, while ciprofloxacin is detected as a high mutagenic activity molecule in E. coli WP2/pKM101 and of low mutagenic activity molecule in S. enterica Serov. typhimurium. It is important to mention that the studied mutagenesis appears at quinolone doses lower to the MIC of each molecule in the assay strains. Having in mind this results the possible implications of the pathogen population exposition to low doses of quinolones is discussed, and it is proposed that these studies are key for the development of new quinolone molecules, which should present both, a higher antibacterial and a low capability of mutagenic activities.
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Síntese e avaliação de fitotoxicidade de (E)-3-estirilquinolin-4(1H)-onas substituídas / Synthesis and phytotoxicity evaluation of substituted (E)-3-estirilquinolin-4 (1H)-onesTapias Isaza, Leidy Johanna 14 March 2014 (has links)
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Previous issue date: 2014-03-14 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / As 4(1H)-quinolonas pertencem a uma classe de compostos de grande utilização e importância na medicina e na área farmacêutica. São substâncias que apresentaram potencial como inibidores da cadeia de transporte de elétrons no fotossistema II durante a fotossíntese. As quinolonas estão distribuídas na natureza como produto do metabolismo secundário de várias espécies de plantas e fungos, principalmente em espécies da família Ruteaceae. No entanto a grande maioria dos derivados quinolônicos existentes no mercado são de origem sintética. No presente trabalho uma série de (E)-3-estirilquinolin-4(1H)-onas foram sintetizadas e avaliadas em termos de suas atividades fitotóxicas. A rota sintética escolhida para o preparo das (E)-3-estirilquinolin-4(1H)-onas iniciou-se com a reação de condensação da 2-aminoacetofenona com formato de metila, obtendo-se a quinolin-4(1H)-ona (85%), cuja reação de iodação resultou na 3-iodoquinolin-4(1H)-ona (82%). A reação de acoplamento cruzado catalisada por paládio (Reação de Heck) foi empregada para a introdução do grupo estiril na quinolona iodada, assim foram obtidas sete diferentes (E)-3-estiril-4(1H)- quinolonas: (E)-3-estirilquinolin-4(1H)-ona (65%), (E)-3-(3-metoxirestiril)-quinolin-4(1H)- ona (41%), (E)-3-(4-metoxiestiril)-quinolin-4(1H)-ona (64%), (E)-3-(4-cloroestiril)-quinolin- 4(1H)-ona (53%), (E)-3-(4-metilestiril)-quinolin-4(1H)-ona (46%), (E)-3-(4-fluoroestiril)- quinolin-4(1H)-ona (72%), (E)-3-(3-fluoroestiril)-quinolin-4(1H)-ona (45%). Sendo quatro delas inéditas a (E)-3-(4-fluoroestiril)-quinolin-4(1H)-ona, (E)-3-(3-fluoroestiril)-quinolin- 4(1H)-ona, (E)-3-(4-metilestiril)-quinolin-4(1H)-ona e (E)-3-(3-metoxiestiril)-quinolin-4(1H)- ona. O potencial fitotóxico dos compostos foi avaliado sobre o desenvolvimento radicular de sorgo (Sorghum bicolor), pepino (Cucumis sativus) em teste de placa de Petri. A (E)-3-(4- cloroestiril)-quinolin-4(1H)-ona, causou inibição significativa sobre o crescimento do sistema radicular de plantas de S. bicolor (80%) na concentração de 500 uM. Com C. sativus sob as mesmas condições os compostos quinolin-4(1H)-ona e (E)-3-(4-metoxiestiril)-quinolin- 4(1H)-ona afetaram o desenvolvimento tanto de raiz (49 e 45%) como da parte aérea (48 e 58%). / The 4 (1H)- quinolone belong to a class of compounds of great use and importance in medicine and in the pharmaceutical field. Are substances that showed potential as inhibitors of the electron transport chain in photosystem II during photosynthesis. The quinolones are distributed in nature as a product of secondary metabolism of various species of plants and fungi, especially in species of the family Ruteaceae. However, the vast majority of existing Quinolone derivatives on the market has synthetic origin. In this study a series of (E)-3- estirilquinolin-4(1H)-ones were synthesized and evaluated in terms of their phytotoxic activity. The synthetic route chosen for the preparation of (E)-3- estirilquinolin-4 (1H)-ones began with the condensation reaction of 2-aminoacetophenone with methyl formate, obtaining a quinolin-4(1H)-one (85%), the iodination reaction which resulted in of 3-iodoquinolin- 4(1H)-one (82%). The reaction of palladium catalyzed cross coupling reaction (Heck) was used for the introduction of the styryl group in the 3-iodoquinolin-4(1H)-one, thereby were obtained seven different (E)-3-styryl-4(1H)-quinolones, (E)-3 styrylquinolin-4(1H)-one (65%) (E)-3-(3-metoxyrstyryl)-quinolin-4(1H)-one (41%), (E)-3-(4-metoxystyryl)-quinolin-4 (1H)-one (64%), (E)-3-(4-chlorostyryl)-quinolin-4(1H)-one (53%), (E)-3-(4-methylstyryl)- quinolin-4(1H)-one (46%), (E)-3-(4-fluorostyryl)-quinolin-4(1H)-one (72%), (E)-3-(3- fluorostyryl)-quinolin-4(1H)-one (45%). Four of which are novel (E)-3-(4-fluorostyryl)- quinolin-4(1H)-one, (E)-3-(3-fluorostyryl)-quinolin-4(1H)–one, (E)-3-(4-methylstyryl)- quinolin-4(1H)-one and (E)-3-(3- metoxystyryl)-quinolin-4(1H)-one. The phytotoxic potential of the compounds was evaluated on the root development of sorghum (Sorghum bicolor), cucumber (Cucumis sativus) in a Petri dish test. The (E)-3-(4-chlorostyryl)-quinolin-4(1H)- one, caused significant inhibition on the growth of the root system of plants of S. bicolor (80%) at the concentration of 500 uM. In C. sativus under the same conditions the compounds quinolin-4(1H)-one and (E)-3-(4-methoxystyryl)-quinolin-4(1H)-one affected the development of both root (49 and 45%) and shoot (48 and 58 %).
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Avaliação in vitro da inibição da atividade de proteínas RAS por derivados de quinolonas no modelo câncer pancreático humanoRedorat, Felipe Silva 31 March 2017 (has links)
Dissertação (mestrado)—Universidade de Brasília, Departamento de Biologia Celular, Programa de Pós-Graduação em Biologia Molecular, 2017. / Submitted by Albânia Cézar de Melo (albania@bce.unb.br) on 2017-06-21T15:23:09Z
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Previous issue date: 2017-07-31 / No Brasil o câncer de pâncreas representa 2% de todos os tipos de câncer, sendo responsável por 4% do total de mortes por essa doença. Seu tratamento raramente se restringe a remoção cirúrgica do tumor devido a elevada agressividade desta doença. Para a maioria dos casos a alternativa terapêutica é a cirurgia e/ou a quimioterapia associada ou não a radioterapia. O câncer de pâncreas é uma doença silenciosa com diagnóstico geralmente tardio, o que dificulta significativamente o tratamento devido a presença de metástases. Este fator também contribui decisivamente para um pobre prognóstico e uma sobrevida após o diagnóstico bastante reduzida, variando de seis a dezoito meses para um grande número de casos. As drogas de primeira escolha para serem utilizadas na quimioterapia desse tipo de câncer, Gencitabina e o 5-fluoracila (5-FU), atuam interferindo com a capacidade celular de sintetizar seu DNA, e assim inibindo a mitose e induzindo a morte celular por apoptose. Em razão dos mecanismos de ação destes fármacos causarem elevada toxicidade para todas as células, o tratamento do câncer de pâncreas está associado a diversos efeitos adversos severos como por exemplo a pancitopenia. Apesar dos avanços terapêuticos para o tratamento do câncer, o câncer de pâncreas persiste como o grande desafio, necessitando urgentemente de alternativas terapêuticas centrais e adjuvantes, que sejam eficientes na eliminação das células tumorais e tumorais com menos toxicidade para às células normais. Com base no acima exposto, nosso grupo passou a avaliar a proteína RAS mutada (KRAS), presente em mais de 40% dos casos de cânceres de pâncreas. Em seguida, nosso grupo sintetizou nove derivados de quinolonas com potencial predito computacionalmente de interferência indireta com a atividade das proteínas RAS. Desta forma, o objeto deste trabalho foi realizar a prova de conceito sobre as propriedades dos derivados das quinolonas atuarem reduzindo ou anulando a atividade anormal de KRAS, na expectativa que este potencial de inibição pudesse contribuir com a redução da taxa de proliferação celular, redução da migração celular e indução da apoptose nestas células tumorais. Embora os agentes aqui avaliados não tenham apresentado resultados promissores para o seu emprego direto, nossos resultados abrem um amplo horizonte para a síntese de outras séries de derivados das quinolonas que com elevado potencial de uso como drogas efetivas no tratamento do câncer de pâncreas. / In the Brazil, pancreatic cancer represents 2% of all cancer types. Accounting for 4% of all deaths from this disease. Its treatment is rarely restricted to the surgical removal of the tumor due to the high aggressiveness of this disease. For most cases the alternative therapy is surgery and/or chemotherapy associated or not with radiotherapy. Pancreatic cancer is a silent disease with a generally late diagnosis, which makes treatment difficult because of metastases presence. This factor also contributes decisively to a poor prognosis and a very short life after diagnosis, ranging from six to eighteen months for many the cases. The first choice drugs that are used in chemotherapy of this type of cancer, Gemcitabine and the 5-fluororacil (5-FU), act interfering with the cellular capacity to synthesize its DNA, thus inhibiting the mitosis and inducing the cell death by apoptosis. Because the mechanisms of action of these drugs cause high toxicity to all cells, the treatment of pancreatic cancer is associated with several severe adverse effects such as pancytopenia. Despite therapeutic advances in the treatment of cancer, pancreatic cancer persists as the major challenge, urgently requiring central therapeutic alternatives and adjuvants, which are efficient in eliminating tumor and tumor cells with less toxicity to normal cells. Based on the above, our group went on to evaluate the RAS protein (KRAS), changed in more than 40% of cases of pancreatic cancers. Next, our group synthesized nine quinolone derivatives with computational potential of indirectly interfering with the activity of RAS proteins. Thus, the objective of this work was to carry out the proof of concept on the properties of the quinolones derivatives to reduce or cancel the abnormal activity of KRAS, in the expectation that this potential inhibition could contribute to the reduction of the rate of cell proliferation, reduction of migration Cell and induction of apoptosis in these tumor cells. Although the agents evaluated here have not presented promising results for their direct use, our results open a wide horizon for the synthesis of other series of quinolone derivatives that with high potential of use as effective drugs in the treatment of pancreatic cancer.
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Dano cerebral e catarata congênita em conceptos de ratas wistar submetidas à peritonite fecal autógena e resposta terapêutica a antimicrobianosMELO, Maria Cecília Santos Cavalcanti 23 December 2015 (has links)
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Previous issue date: 2015-12-23 / CAPEs / Objetivo: Investigar as alterações dos encéfalos e olhos de conceptos recém-nascidos
de ratas que se submeteram a peritonite fecal autógena e avaliar as respostas com a
intervenção de dois esquemas terapêuticos com moxifloxacino-dexametasona e
meropenem realizados durante a prenhez. Métodos: Foram incluídas, de forma
aleatória, 30 ratas Wistar para acasalamento. Dessas, 15 ratas tiveram esfregaço vaginal
positivo para prenhez. O experimento foi realizado em duas fases:
1. Desenvolvimento do modelo experimental: As ratas foram distribuídas em : AGrupo
estudo com cinco ratas após peritonite fecal autógena com suspensão de fezes a
10 %, na dose de três ml/Kg no nono dia de prenhez, B- Grupo estudo com cinco ratas
após peritonite fecal autógena com suspensão de fezes a 10 %, na dose de quatro ml/Kg
no nono dia de prenhez e C- grupo de cinco ratas prenhes sem peritonite fecal autógena
(controle). Após o parto, foi realizada a eutanásia e o inventário das cavidades
abdominal e torácica das ratas dos grupos estudo A e B e os dados de seus conceptos.
2.Intervenção com esquemas terapêuticos: Grupo1: Duas ratas prenhes após peritonite
fecal autógena com suspensão de fezes a 10 %, na dose de quatro ml/Kg no nono dia de
prenhez que receberam moxifloxacino - dexametasona intraperitoneal em 48 e 72
horas e Grupo 2: Duas ratas prenhes após peritonite fecal autógena com suspensão de
fezes a 10 %, na dose de quatro ml/Kg no nono dia de prenhez que receberam
meropenem intravenoso em 48 e 72 horas. Após o parto, foi realizada a eutanásia e o
inventário das cavidades abdominal e torácica destas e a decapitação com inspeção do
crânio, da consistência dos cérebros e os olhos de todos os conceptos. O projeto foi
aprovado pelo Comitê de Ética da Faculdade de Ciências Médicas de Campina Grande-
Paraíba. P ≤ 0.05 foi usado para rejeição da hipótese de nulidade. Resultados: O
modelo de peritonite fecal autógena selecionado foi o que utilizou a dose de quatro
ml/Kg da suspensão de fezes a 10%. Das 15 ratas com esfregaço vaginal positivo dez
estavam prenhas, sendo três no grupo A, quatro no grupo B e três no grupo C. Os
cérebros dos conceptos das ratas que receberam quatro ml/kg da suspensão de fezes a
10% se mostraram, significantemente, menores e com consistência menos firme que
aqueles do grupo controle, assim como, comparados com os das intervenções
terapêuticas. Cataratas congênitas foram observadas em nove de 26 (34,6%) conceptos
das ratas que receberam quatro ml/Kg da suspensão de fezes a 10% e não receberam
intervenção terapêutica, sendo sete bilateral e dois unilateral. Nenhuma catarata
congênita foi observada nos 20 recém-nascidos das ratas que receberam a combinação
de moxifloxacino - dexametasona intraperitoneal. Catarata congênita foi observada em
três (13.6%) dos 22 recém-nascidos das ratas que receberam meropenem intravenoso.
Conclusões: Septicemia gestacional em ratas pode produzir alteração cerebral e catarata
congênita nos conceptos. Com a utilização dos esquemas terapêuicos, nas ratas prenhas
submetidas à peritonite fecal autógena com a dose de quatro ml/Kg da suspensão de
fezes a 10%, houve menor número de casos de conceptos com alterações encefálicas e
oculares. / Purpose: To investigate the abnormalities of brains and eyes of newborn fetuses of rats
that underwent autologous fecal peritonitis and evaluate the responses with the
intervention of two treatment regimens with moxifloxacin and meropenem -
dexamethasone performed during pregnancy. Methods: Randomly, 30 Wistar rats for
mating. Of these, 15 rats had a positive vaginal smear for pregnancy. The experiment
was conducted in two phases:
1. Development the experimental model: The rats were divided into: Group A- study
with five rats after fecal peritonitis autogenous with faeces of a 10% suspension at a
dose of three ml/kg on the ninth day of pregnancy, group B study with five rats after
fecal peritonitis autogenous with faeces of a 10% suspension at a dose four ml/kg on the
ninth day of pregnancy and C-group of five pregnant rats without autologous fecal
peritonitis (control). After delivery, euthanasia and inventory of abdominal and thoracic
cavities of study groups A and B and the data of their fetuses.
2.Intervention with therapeutic regimens : Group 1 : Two pregnant rats after fecal
peritonitis autogenous suspension of faeces to 10 % at a dose four ml / kg on the ninth
day of pregnancy who received moxifloxacin - intraperitoneal dexamethasone at 48 and
72 hours and Group 2 : Two pregnant rats, autogenous after peritonitis with stool
suspension at 10 % in doses four ml / kg on the ninth day of pregnancy who received
intravenous meropenem in 48 and 72 hours. After delivery, euthanasia and inventory of
abdominal and chest cavities of these and the beheading with skull inspection was
carried, the consistency of the brain and the eyes of all fetuses . The project was
approved by the Ethics Committee of the Faculty of Medical Sciences of Campina
Grande - Paraíba. P ≤ 0.05 was used to reject the null hypothesis. Results: The fecal
peritonitis autogenous model selected was that using 10% faeces suspension at a dose
four ml/kg. Of the 15 rats with positive vaginal smear ten were pregnant, three in group
A, four in group B and three in group C. The brains of fetuse of rats given four ml/kg of
10% faeces suspension is shown, significantly, smaller and less firm consistency than
those of the control group, as compared with the therapeutic interventions. Congenital
cataract was observed in nine of 26 (34.6%) fetuses of rats given four ml/kg of 10%
faeces suspension received no therapeutic intervention, seven bilateral and two
unilateral. No congenital cataract was observed in 20 newborns of rats given the
combination of intraperitoneal moxifloxacin - dexamethasone. Congenital cataract was
observed in three (13.6%) of 22 infants of rats given intravenous meropenem.
Conclusions: Gestational septicemia in rats can produce brain abnormalities and
congenital cataracts in fetuses. With the use of treatment regimens, in pregnant rats
submitted autologous fecal peritonitis with a dose of four ml/kg of 10% faeces
suspension, there were few cases of fetuses with brain and eye abnormalities.
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