RESUMO
The main objective of the study is to analyse the scientific evolution of the research field of fibromyalgia and biomechanics. A search was carried out in Web of Science, from 1985 to 2021. With those results, a bibliometric map of keywords was created with VOSviewer. On top of that, scientific mapping and performance analysis were also conducted using SciMAT. A total of 233 articles from around the world were analysed, highlighting the production of the USA and Spain. The results show great diversity in topics with 54 different topics and 33 keywords. Although most of the topics found are not widely developed except the topics of physical activity and symptomatology. In conclusion, the study of fibromyalgia and biomechanics has generally grown over time.
Assuntos
Fibromialgia , Bibliometria , Fenômenos Biomecânicos , Humanos , EspanhaRESUMO
The main objectives of this study were (i) to evaluate the serum pharmacokinetic behaviour and milk penetration of marbofloxacin (MFX; 5 mg/kg), after intravenous (IV) and intramuscular (IM) administration in lactating goats and simulate a multidose regimen on steady-state conditions, (ii) to determine the minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) of coagulase negative staphylococci (CNS) isolated from caprine mastitis in Córdoba, Argentina and (iii) to make a PK/PD analysis by Monte Carlo simulation from steady-state pharmacokinetic parameters of MFX by IV and IM routes to evaluate the efficacy and risk of the emergence of resistance. The study was carried out with six healthy, female, adult Anglo Nubian lactating goats. Marbofloxacin was administered at 5 mg/kg bw by IV and IM route. Serum and milk concentrations of MFX were determined with HPLC/uv. From 106 regional strains of CNS isolated from caprine mastitis in herds from Córdoba, Argentina, MICs and MPCs were determined. MIC90 and MPC90 were 0.4 and 6.4 µg/ml, respectively. MIC and MPC-based PK/PD analysis by Monte Carlo simulation indicates that IV and IM administration of MFX in lactating goats may not be adequate to recommend it as an empirical therapy against CNS, because the most exigent endpoints were not reached. Moreover, this dose regimen could increase the probability of selecting mutants and resulting in emergence of resistance. Based on the results of Monte Carlo simulation, the optimal dose of MFX to achieve an adequate antimicrobial efficacy should be 10 mg/kg, but it is important take into account that fluoroquinolones are substrates of efflux pumps, and this fact may determine that assumption of linear pharmacokinetics at high doses of MFX may be incorrect.
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Antibacterianos/farmacocinética , Fluoroquinolonas/farmacocinética , Leite/química , Animais , Antibacterianos/administração & dosagem , Antibacterianos/análise , Cromatografia Líquida de Alta Pressão/veterinária , Feminino , Fluoroquinolonas/administração & dosagem , Fluoroquinolonas/análise , Fluoroquinolonas/uso terapêutico , Doenças das Cabras/tratamento farmacológico , Cabras/metabolismo , Injeções Intramusculares/veterinária , Injeções Intravenosas/veterinária , Lactação/metabolismo , Mastite/tratamento farmacológico , Mastite/veterinária , Testes de Sensibilidade Microbiana , Método de Monte CarloRESUMO
INTRODUCTION: Electroconvulsive therapy (ECT) is most frequently indicated for episodes of melancholic depression, but is also useful in the treatment of maniac syndrome and some schizophrenia subtypes. ECT is part of the treatment of movement disorders, neuroleptic malignant syndrome and even in the treatment of severe conversions. Although the therapeutic results are excellent when used appropriately, the mortality rate is estimated between 2 and 4 for 100,000 shocks. Despite this mortality rate, the benefit-risk ratio remains very positive and serious complications are extremely rare. ECT results in a biphasic cardiological effect: firstly a perstimulus parasympathetic hypertonia contemporary to the seizure's tonic phase, then a phase of contemporary sympathetic hypertonia during the epileptic clonic movement. We will focus on the perstimulus asystole as it is by far the most frequent. Very few cases and even less studies have been referenced in the literature; here, we present a clinical case followed by a discussion. CLINICAL CASE: The patient is in his fifties and has been treated for many years for a unipolar mood disorder with recurrent melancholic depressive episodes. With each new depressive episode, the clinical evolution is rapidly positive after a few sessions of ECT. Maintenance ECT was not retained due to the supra-annual periodicity of the melancholic depressive episodes and rapid recovery after electric treatment. Then, this patient developed another depressive decline in mood comparable to the previous one, despite adapted blood lithium levels associated with a new generation antidepressant treatment. According to his history, a hospitalisation was programmed to carry out a new course of ECT. Considering the short duration of the first seizures, the intensity of the stimulus was progressively increased. At 180 joules, the patient presented an immediate per-stimulus asystole of 20seconds which ceased spontaneously. The specialized cardiologic consultation following the rhythmic episode was reassuring: the patient's cardiac condition remained stable. However, after discussion with the patient and his family, we decided to stop the ECT. Was this a reasonable decision? DISCUSSION: According to the literature, the patient's medical history, sex, psychiatric diagnosis, the shock parameters (level of energy applied, duration of the stimulus, number of shocks) and clinical results, are not predictive factors in the occurrence of an asystole. Concerning the ECT protocol, the vagus nerve seems less stimulated during bifrontal stimulations in opposition to unilateral stimulations. Perasystolic patients are younger and have less prior history of cardiovascular disease or ECG abnormalities. Although the patients receiving ECT are often taking several medications (antipsychotics, benzodiazepines, antidepressants, anticholinergic correctors, calcium channel blockers, loop diuretics, converting enzyme inhibitors), these drugs are not considered as facilitating asystoles. No increase in the frequency of asystole had been observed when taking an average dose psychotropic treatment allowing the continuation of an antidepressant treatment at the recommended dose. Differently, lithium is regularly stopped during the shock phase as it could - even a few days after being stopped - potentiate the effects of succinylcholine and increase the vagal tone. Succinylcholine seems to promote asystole, whilst caffeine, methohexital and trimethaphan do not. The hypersympathetic phase can be controlled by a betablocker (propranolol, esmolol, labetalol) that does not increase the prior risk of asystole. Anticholinergic premedication using atropine does not appear to be systematic and could even potentially induce tachy-dysarrhythmia. However, in the case of perstimulus asystole, most authors recommend continuing the shocks with doses of atropine around 0.4 to 1mg. PHYSIOPATHOLOGY: Vagal stimulation is preferentially central and directly linked to the electric excitation of the lateral dorsal motor nucleus of the vagus nerve. Younger patients with no cardiac history are more at risk. This could be explained by the fact that juvenile tissue conducts electricity more rapidly than senescent (the difference being probably due to the fibrosis and adipose tissue which reduce its conductive capacity). Finally, it is appropriate to question the direct therapeutic aspect of vagal stimulation which constitutes an experimental treatment of resistant depression. CONCLUSIONS: The occurrence of perstimulus asystole is not considered as a serious complication of ECT and therefore as a contra-indication to any future sessions. On the contrary, most authors are campaigning for the continuation of shocks with the possibility of adding prophylactic intravenous atropine. Cardiac arrest reminds us that ECT requires a special attention to its cardiovascular effect, which emphasizes the role of interdisciplinarity between anaesthesiologists and psychiatrists.
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Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/terapia , Eletroconvulsoterapia/efeitos adversos , Parada Cardíaca/etiologia , Envelhecimento , Anestesia , Antiarrítmicos/uso terapêutico , Atropina/uso terapêutico , Contraindicações , Condutividade Elétrica , Parada Cardíaca/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estimulação do Nervo VagoRESUMO
1. The objective of the study was to evaluate the comparative pharmacokinetic behaviour of enrofloxacin in adult ostriches after single and multiple intramuscular (IM) and subcutaneous (SC) administrations. In addition, tissue tolerance was evaluated. 2. Enrofloxacin was well absorbed, but showed a short permanence after both administration routes. After multiple dose administrations the maximum and minimum peak plasma concentrations were very similar for both routes, obtaining a steady state phase from the second dose that extended until the last evaluated administration. 3. There was no significant accumulation after multiple IM or SC doses; however, there were differences in a fluctuation index after multiple intramuscular administrations that could be related to muscle damage. 4. The different microbiological efficacy indicators (PK/PD indices) obtained, the pharmacokinetic behaviour and CK serum concentrations suggest that subcutaneous enrofloxacin administration of 15 mg/kg every 12 h produce and maintain an efficient concentration of antibiotic that is a safer and more effective therapeutic option than intramuscular administration.
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Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Fluoroquinolonas/administração & dosagem , Fluoroquinolonas/farmacocinética , Struthioniformes/metabolismo , Animais , Antibacterianos/sangue , Ciprofloxacina/administração & dosagem , Ciprofloxacina/sangue , Estudos Cross-Over , Enrofloxacina , Feminino , Fluoroquinolonas/sangue , Injeções Intramusculares , Injeções Subcutâneas , MasculinoRESUMO
INTRODUCTION: Cardiac myxoma is an important but uncommon cause of stroke in younger patients. Few published case series analyse the frequency and clinical presentation of neurological complications in patients with myxoma. OBJECTIVE: To list all neurological complications from cardiac myxoma recorded in our hospital in the past 28 years. PATIENTS AND METHODS: We retrospectively reviewed the neurological manifestations of cardiac myxoma in patients treated in our hospital between December 1983 and March 2012. RESULTS: Of the 36 patients with cardiac myxoma, 8 (22%) presented neurological manifestations. Half were women and mean age of patients was 52.4 ± 11.6 years. Sudden-onset hemiparesis was the most frequent neurological symptom (63%). Established ischaemic stroke was the most common clinical manifestation (75%), followed by transient ischemic attack. The most commonly affected territory corresponded to the middle cerebral artery. Myxoma was diagnosed by echocardiography in all cases. Mean myxoma size was 4.1cm and most of the tumours (63%) had a polypoid surface. All tumours were successfully removed by surgery. There were no in-hospital deaths. CONCLUSIONS: Cardiac myxomas frequently present with neurological symptoms, especially ischaemic events (established stroke or transient ischaemic attack), in younger patients with no cardiovascular risk factors. The anterior circulation is more frequently affected, especially the middle cerebral artery. Echocardiography can facilitate prompt diagnosis and early treatment of the lesion.
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Neoplasias Cardíacas/complicações , Mixoma/complicações , Doenças do Sistema Nervoso/etiologia , Adulto , Isquemia Encefálica/etiologia , Eletrocardiografia , Feminino , Seguimentos , Neoplasias Cardíacas/patologia , Humanos , Infarto da Artéria Cerebral Média/etiologia , Masculino , Pessoa de Meia-Idade , Mixoma/patologia , Doenças do Sistema Nervoso/patologia , Neuroimagem , Paresia/etiologia , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologia , Resultado do TratamentoRESUMO
From a human safety perspective, the administration of ivermectin to food producing animal species entails potential risks related to the presence of drug residues in edible tissues, milk, and other derived products. The European Medicines Agency has established the maximum residue limits for ivermectin in the European Union, with values of 100 µg·kg(-1) in fat and liver and 30 µg·kg(-1) in kidney for all mammalian food producing species, in order to ensure that the amount of ivermectin that can be found in animal foodstuff is below dangerous levels for the consumers. According to these values, withdrawal periods after subcutaneous injection were recently established in the European Union (2009), in 49 days for products containing ivermectin as a single active substance or in combination with closantel, and in 66 days when combined with clorsulon. The marker residue for ivermectin was found to be H(2)B(1a), which is the major component of the parent compound. The tissue distribution of residues and the overall ratios of marker to total residues were generally similar in most species, and the highest concentrations of ivermectin residues were found in fat and liver with high levels also detected in injection site muscles. Ivermectin is not licensed for use in animals from which milk is produced for human consumption, however its extra-label use should be considered regarding human safety, due to its long persistence in milk and milk-derived products.
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Antiparasitários/análise , Resíduos de Drogas/análise , Contaminação de Alimentos/análise , Ivermectina/análise , Animais , Humanos , Carne/análise , Leite/químicaAssuntos
Antibacterianos/farmacocinética , Anti-Inflamatórios não Esteroides/farmacocinética , Búfalos/metabolismo , Fluoroquinolonas/farmacocinética , Animais , Animais Recém-Nascidos , Antibacterianos/sangue , Antibacterianos/farmacologia , Anti-Inflamatórios não Esteroides/sangue , Anti-Inflamatórios não Esteroides/farmacologia , Área Sob a Curva , Interações Medicamentosas , Fluoroquinolonas/sangue , Fluoroquinolonas/farmacologia , Injeções Intramusculares/veterinária , CinéticaRESUMO
BACKGROUND: CODIS-STRs in Native Mexican groups have rarely been analysed for human identification and anthropological purposes. AIM: To analyse the genetic relationships and population structure among three Native Mexican groups from Mesoamerica. SUBJECTS AND METHODS: 531 unrelated Native individuals from Mexico were PCR-typed for 15 and 9 autosomal STRs (Identifiler™ and Profiler™ kits, respectively), including five population samples: Purépechas (Mountain, Valley and Lake), Triquis and Yucatec Mayas. Previously published STR data were included in the analyses. RESULTS: Allele frequencies and statistical parameters of forensic importance were estimated by population. The majority of Native groups were not differentiated pairwise, excepting Triquis and Purépechas, which was attributable to their relative geographic and cultural isolation. Although Mayas, Triquis and Purépechas-Mountain presented the highest number of private alleles, suggesting recurrent gene flow, the elevated differentiation of Triquis indicates a different origin of this gene flow. Interestingly, Huastecos and Mayas were not differentiated, which is in agreement with the archaeological hypothesis that Huastecos represent an ancestral Maya group. Interpopulation variability was greater in Natives than in Mestizos, both significant. CONCLUSION: Although results suggest that European admixture has increased the similarity between Native Mexican groups, the differentiation and inconsistent clustering by language or geography stresses the importance of serial founder effect and/or genetic drift in showing their present genetic relationships.
Assuntos
Etnicidade/genética , Indígenas Norte-Americanos/genética , Repetições de Microssatélites , Demografia , Genética Forense , Amplificação de Genes , Fluxo Gênico , Frequência do Gene , Deriva Genética , Marcadores Genéticos , Variação Genética , Genótipo , Geografia , Haplótipos , Humanos , México , Técnicas de Diagnóstico Molecular , Reação em Cadeia da Polimerase , População Branca/genéticaRESUMO
Dysregulation of gene expression is one of the mechanisms involved in the pathophysiology of Huntington's disease (HD). Here, we examined whether mutant huntingtin regulates the levels of PH domain leucine-rich repeat protein phosphatase 1 (PHLPP1), a phosphatase that specifically dephosphorylates Akt at Ser473. Our results show decreased PHLPP1 protein levels in knock-in models (Hdh(Q111/Q111) mouse striatum and STHdh(Q111/Q111) cells), in the striatum of N-terminal exon-1 mutant huntingtin transgenic mouse models (R6/1; R6/1 : BDNF + or - , R6/2 and Tet/HD94) and in the putamen of HD patients. Quantitative PCR analysis revealed a reduction in PHLPP1 mRNA levels in the striatum of R6/1 compared with wild-type mice. Coincident with reduced PHLPP1 protein levels, we observed increased phosphorylated Akt (Ser473) levels specifically in the striatum. The analysis of the conditional mouse model Tet/HD94 disclosed that after mutant huntingtin shutdown PHLPP1 levels returned to wild-type levels whereas phospho-Akt levels were partially reduced. In conclusion, our results show that mutant huntingtin downregulates PHLPP1 expression. In the striatum, these reduced levels of PHLPP1 can contribute to maintain high levels of activated Akt that may delay cell death and allow the recovery of neuronal viability after mutant huntingtin silencing.
Assuntos
Corpo Estriado/enzimologia , Doença de Huntington/enzimologia , Proteínas Nucleares/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosfoproteínas Fosfatases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Adulto , Idoso , Animais , Morte Celular/fisiologia , Linhagem Celular Transformada , Núcleo Celular/metabolismo , Corpo Estriado/patologia , Citosol/metabolismo , Modelos Animais de Doenças , Éxons/genética , Feminino , Técnicas de Introdução de Genes , Humanos , Doença de Huntington/genética , Doença de Huntington/patologia , Masculino , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Neurotoxinas/metabolismo , Proteínas Nucleares/química , Proteínas Nucleares/genética , Fosfoproteínas Fosfatases/química , Fosfoproteínas Fosfatases/genética , Fosforilação/fisiologia , Estrutura Terciária de ProteínaRESUMO
Tauopathies with parkinsonism represent a spectrum of disease entities unified by the pathologic accumulation of hyperphosphorylated tau protein fragments within the central nervous system. These pathologic characteristics suggest shared pathogenetic pathways and possible molecular targets for disease-modifying therapeutic interventions. Natural history studies, for instance, in progressive supranuclear palsy, frontotemporal dementia with parkinsonism linked to chromosome 17, corticobasal degeneration, and Niemann-Pick disease type C as well as in amyotrophic lateral sclerosis/Parkinson-dementia complex permit clinical characterization of the disease phenotypes and are crucial to the development and validation of biological markers for differential diagnostics and disease monitoring, for example, by use of neuroimaging or proteomic approaches. The wide pathologic and clinical spectrum of the tauopathies with parkinsonism is reviewed in this article, and perspectives on future advances in the understanding of the pathogenesis are given, together with potential therapeutic strategies.
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Transtornos Parkinsonianos/complicações , Tauopatias/complicações , Animais , Biomarcadores , Demência/complicações , Demência/genética , Demência/fisiopatologia , Desenho de Fármacos , Geografia , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Modelos Biológicos , Mutação , Doença de Niemann-Pick Tipo C/complicações , Doença de Niemann-Pick Tipo C/diagnóstico , Doença de Niemann-Pick Tipo C/fisiopatologia , Doença de Parkinson Pós-Encefalítica/complicações , Doença de Parkinson Pós-Encefalítica/fisiopatologia , Transtornos Parkinsonianos/patologia , Transtornos Parkinsonianos/fisiopatologia , Transtornos Parkinsonianos/terapia , Doença de Pick/complicações , Doença de Pick/patologia , Proteínas Serina-Treonina Quinases/genética , Paralisia Supranuclear Progressiva/complicações , Paralisia Supranuclear Progressiva/diagnóstico , Paralisia Supranuclear Progressiva/fisiopatologia , Tauopatias/patologia , Tauopatias/fisiopatologia , Tauopatias/terapia , Proteínas tau/genéticaRESUMO
Glycogen synthase kinase-3beta (GSK-3beta) has been proposed as the main kinase able to phosphorylate tau aberrantly in Alzheimer's disease and in related tauopathies. We have previously generated a double transgenic mouse line overexpressing the enzyme GSK-3beta and tau protein carrying a triple frontotemporal dementia and parkinsonism linked to chromosome 17 mutation whose expression patterns overlap in CA1 (pyramidal neurons) and dentate gyrus (granular neurons). Here, we have used this transgenic model to analyze how axonal and somatodendritic neuronal compartments are affected in the hippocampus. Our data demonstrate that neuronal subpopulations respond differentially to increased GSK-3 activity. Thus, dentate gyrus granular neurons undergo apoptotic death with subsequent degeneration of the mossy fibers, while CA1 pyramidal neurons accumulate hyperphosphorylated tau both in the axonal and in the somatodendritic compartments. These studies also allow us to propose a model of spreading of pathology through the hippocampus as a consequence of GSK-3 and tau dysregulation.
Assuntos
Diferenciação Celular/genética , Quinase 3 da Glicogênio Sintase/genética , Hipocampo/citologia , Neurônios/classificação , Neurônios/fisiologia , Proteínas tau/genética , Fatores Etários , Animais , Anticorpos Monoclonais/metabolismo , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/genética , Caspase 3/metabolismo , Cromossomos Humanos Par 17/genética , Modelos Animais de Doenças , Proteína Glial Fibrilar Ácida/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Humanos , Indóis , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microscopia Eletrônica de Transmissão , Mutação/genética , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/patologia , Neurônios/ultraestrutura , Proteínas tau/metabolismoRESUMO
C(2)H(4) is associated with plant defense, but its role during the hypersensitive response (HR) remains largely uncharacterized. C(2)H(4) production in tobacco (Nicotiana tabacum) following inoculation with HR-eliciting Pseudomonas syringae pathovars measured by laser photoacoustic detection was biphasic. A first transient rise (C(2)H(4)-I) occurred 1 to 4 h following inoculation with HR-eliciting, disease-forming, and nonpathogenic strains and also with flagellin (flg22). A second (avirulence-dependent) rise, at approximately 6 h (C(2)H(4)-II), was only seen with HR-eliciting strains. Tobacco leaves treated with the C(2)H(4) biosynthesis inhibitor, aminoethoxyvinylglycine, suggested that C(2)H(4) influenced the kinetics of a HR. Challenging salicylate hydroxylase-expressing tobacco lines and tissues exhibiting systemic acquired resistance suggested that C(2)H(4) production was influenced by salicylic acid (SA). Disrupted expression of a C(2)H(4) biosynthesis gene in salicylate hydroxylase tobacco plants implicated transcriptional control as a mechanism through which SA regulates C(2)H(4) production. Treating leaves to increase oxidative stress or injecting with SA initiated monophasic C(2)H(4) generation, but the nitric oxide (NO) donor sodium nitroprusside initiated biphasic rises. To test whether NO influenced biphasic C(2)H(4) production during the HR, the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester was coinoculated with the avirulent strain of P. syringae pv phaseolicola into tobacco leaves. The first transient C(2)H(4) rise appeared to be unaffected by N(G)-nitro-L-arginine methyl ester, but the second rise was reduced. These data suggest that NO and SA are required to generate the biphasic pattern of C(2)H(4) production during the HR and may influence the kinetics of HR formation.
Assuntos
Etilenos/metabolismo , Nicotiana/metabolismo , Óxido Nítrico/fisiologia , Salicilatos/metabolismo , Etilenos/antagonistas & inibidores , Glicina/análogos & derivados , Glicina/farmacologia , Oxigenases de Função Mista/metabolismo , Doadores de Óxido Nítrico/farmacologia , Nitroprussiato/farmacologia , Estresse Oxidativo , Pseudomonas syringae/fisiologia , Nicotiana/enzimologia , Nicotiana/microbiologiaRESUMO
Alzheimer's disease is characterized by the presence of two histopathological aberrant structures, the senile plaques and the neurofibrillary tangles. The main component of these tangles is the cytoskeletal protein tau in hyperphosphorylated form. Since a main tau kinase is glycogen synthase kinase 3 (GSK-3), the use of specific GSK-3 inhibitors, like lithium, could be a potential therapy in Alzheimer's disease. In this short article, we have done a review on tau phosphorylation in Alzheimer's disease and other tauopathies, and on the inhibition of kinases like GSK-3, involved in tau modification.
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Doença de Alzheimer/tratamento farmacológico , Compostos de Lítio/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Doença de Alzheimer/enzimologia , Doença de Alzheimer/patologia , Animais , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Humanos , Compostos de Lítio/farmacologia , Fármacos Neuroprotetores/farmacologiaRESUMO
This study compared pharmacokinetic profiles in cattle dosed subcutaneously with two different formulations of enrofloxacin (5% and 10%) at a dose of 5 mg/kg. Plasma concentrations of enrofloxacin and its active metabolite, ciprofloxacin, were determined by a HPLC/u.v. method. The pharmacokinetic parameters of enrofloxacin and its metabolite were similar in both injectable formulations. Enrofloxacin peak plasma concentration (5%: 0.73 +/- 0.32; 10%: 0.60 +/- 0.14 microg/mL) was reached at 1.21 +/- 0.52 and 1.38 +/- 0.52 h to 5 and 10%, respectively. The terminal half-live and area under curve were 2.34 +/- 0.46 and 2.59 +/- 0.46 h, and 3.09 +/- 0.81 and 2.93 +/- 0.58 microg x h/mL, to 5 and 10%, respectively. The AUC/MIC(90) and Cmax/MIC(90) ratios for both formulations exceed the proposed threshold values for optimized efficacy and minimized resistance development whilst treating infections or septicaemia caused by P. multocida and E. coli.
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Antibacterianos/farmacocinética , Bovinos/metabolismo , Ciprofloxacina/farmacocinética , Fluoroquinolonas/farmacocinética , Animais , Antibacterianos/sangue , Antibacterianos/toxicidade , Bovinos/sangue , Ciprofloxacina/sangue , Enrofloxacina , Fluoroquinolonas/sangue , Fluoroquinolonas/uso terapêutico , MasculinoRESUMO
Ubiquitylated inclusion bodies (IBs) found in Huntington's disease (HD) postulate an impaired ubiquitin-proteasome system. However, this hypothesis remains controversial. In vitro-generated polyglutamine aggregates failed to inhibit purified proteasomes, while filamentous huntingtin aggregates isolated from mice resulted in inhibition. However, similarly isolated IBs did not, thus suggesting that IB formation is protective by sequestering smaller inhibitory aggregates. Accordingly, proteasome-activity assays in IB-containing mouse brain homogenates did not show decreased activity. On the contrary, some of the endoproteolytic proteasome activities increased, probably due to altered subunit composition. However, activity was found decreased in postmortem human HD tissue. Finally, evidence supporting the hypothesis was found in HD cell models expressing fluorescent ubiquitin-proteasome system reporters but not in retina of SCA-7 mice with similar reporters. In summary, it seems that mutant huntingtin, probably in intermediate aggregate forms, has the potential to inhibit proteasome activity, but the global status of the system in HD brain tissue is not yet fully elucidated.
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Doença de Huntington/enzimologia , Complexo de Endopeptidases do Proteassoma/fisiologia , Ubiquitina/fisiologia , Animais , Genes Reporter , Humanos , Proteína Huntingtina , Proteínas Luminescentes/análise , Camundongos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/fisiologia , Proteínas Nucleares/genética , Proteínas Nucleares/fisiologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Inibidores de ProteassomaRESUMO
Six donkeys each received 2 mg/kg marbofloxacin as a 10 per cent aqueous solution administered intravenously. Principal pharmacokinetic parameters were determined and two efficacy indices were computed by using pharmacokinetic parameters and selected mic90 values of marbofloxacin against pathogenic equine strains to predict the efficacy of the drug at this dose. The pharmacokinetics of marbofloxacin in donkeys was characterised by a large mean volume of distribution at a steady state (1.15 [0.09] l/kg) and a long mean (sd) elimination half-life of 9.24 (1.96) hours. It was also characterised by a relatively slow total body clearance of 0.10 (0.02) l/kg/hour, slower than in horses. Using mic90 values of marbofloxacin against pathogenic equine strains with a daily dose of 2 mg/kg, appropriate values of efficacy indicators were obtained only for Enterobacteriaceae. Daily intravenous doses of 0.33, 2.62 and 20 mg/kg were calculated for evaluation in clinical trials of infections due to Enterobacteriaceae, Staphylococcus aureus and Streptococci, respectively.
Assuntos
Antibacterianos/farmacocinética , Infecções Bacterianas/veterinária , Equidae/metabolismo , Fluoroquinolonas/farmacocinética , Cavalos/metabolismo , Quinolonas/farmacocinética , Animais , Área Sob a Curva , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/metabolismo , Equidae/sangue , Feminino , Meia-Vida , Doenças dos Cavalos/tratamento farmacológico , Doenças dos Cavalos/metabolismo , Cavalos/sangue , Injeções Intravenosas/veterinária , Masculino , Taxa de Depuração Metabólica , Especificidade da Espécie , Resultado do TratamentoRESUMO
Ketamine is a short-acting dissociative anaesthetic for chemical restraint and surgical anaesthesia in domestic and non-domestic animals. The present study was designed to determine the pharmacokinetics of a single dose of ketamine (10 mg/kg) after intramuscular (i.m.) administration to young ostriches premedicated with romifidine. Ketamine was rapidly absorbed after i.m. administration. Maximal ketamine concentration (C(max)) of 2.93 +/- 0.61 microg/ml was reached at 12.5 +/- 2.50 min and thereafter ketamine concentrations decreased rapidly. The elimination half-life (t(1/2 z)) obtained was 62.37 +/- 17.37 min and mean residence time (MRT) was 77.33 +/- 19.12 min. The area under the curve (AUC) was 114.19 +/- 15.76 microg x min/ml.
Assuntos
Anestésicos Dissociativos/farmacocinética , Ketamina/farmacocinética , Struthioniformes/fisiologia , Anestesia/métodos , Anestesia/veterinária , Anestésicos/farmacologia , Animais , Área Sob a Curva , Imidazóis/farmacologia , Injeções Intramusculares/veterinária , Taxa de Depuração Metabólica , Struthioniformes/sangue , Struthioniformes/metabolismoRESUMO
BACKGROUND AND AIMS: The relationship between ethylene production and both seed dormancy and germination was investigated using red rice (weedy rice) as a model species. METHODS: Both fully dormant and after-ripened (non-dormant) naked caryopses were incubated with or without inhibitors of ethylene synthesis [aminoethoxyvinylglycine (AVG)] and perception [silver thiosulfate (STS)], or in the presence of the natural ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC). The kinetics of ethylene emissions were measured with a sensitive laser-photoacoustic system. KEY RESULTS: Dormant red rice caryopses did not produce ethylene. In non-dormant caryopses, ethylene evolution never preceded the first visible stage of germination (pericarp splitting), and ethylene inhibitors completely blocked ethylene production, but not pericarp splitting. Accordingly, endogenous ACC appeared to be lacking before pericarp splitting. However, early seedling growth (radicle or coleoptile attaining the length of 1 mm) followed ethylene evolution and was delayed by the inhibitors. Wounding the dormant caryopses induced them to germinate and produce ethylene, but their germination was slow and pericarp splitting could be speeded up by ethylene. CONCLUSIONS: The findings suggest that, in red rice, endogenous ethylene stimulates the growth of the nascent seedling, but does not affect seed dormancy or germination inception. Correspondingly, this phytohormone does not play a role in the dormancy breakage induced by wounding, but accelerates germination after such breakage has occurred.
Assuntos
Etilenos/biossíntese , Germinação , Oryza/metabolismo , Reguladores de Crescimento de Plantas/biossíntese , Aminoácidos Cíclicos/farmacologia , Etilenos/antagonistas & inibidores , Glicina/análogos & derivados , Glicina/farmacologia , Oryza/embriologia , Oryza/crescimento & desenvolvimento , Reguladores de Crescimento de Plantas/antagonistas & inibidores , Sementes/efeitos dos fármacos , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , Tiossulfatos/farmacologiaRESUMO
During anaerobiosis in darkness the main route for ATP production in plants is through glycolysis in combination with fermentation. We compared the organ-specific anaerobic fermentation of flooding-tolerant rice (Oryza sativa) and sensitive wheat (Triticum aestivum) seedlings. A sensitive laser-based photoacoustic trace gas detection system was used to monitor emission of ethanol and acetaldehyde by roots and shoots of intact seedlings. Dark-incubated rice seedlings released 3 times more acetaldehyde and 14 times more ethanol than wheat seedlings during anaerobiosis. Ninety percent of acetaldehyde originated from shoots of both species. In comparison to wheat shoots, the high ethanol production of rice shoots correlated with larger amounts of soluble carbohydrates, and higher activities of fermentative enzymes. After 24 h of anaerobiosis in darkness rice shoots still contained 30% of aerated ATP level, which enabled seedlings to survive this period. In contrast, ATP content declined almost to zero in wheat shoots and roots, which were irreversibly damaged after a 24-h anaerobic period. When plants were anaerobically and dark incubated for 4 h and subsequently transferred back to aeration, shoots showed a transient peak of acetaldehyde release indicating prompt re-oxidation of ethanol. Post-anoxic acetaldehyde production was lower in rice seedlings than in wheat. This observation accounts for a more effective acetaldehyde detoxification system in rice. Compared to wheat the greater tolerance of rice seedlings to transient anaerobic periods is explained by a faster fermentation rate of their shoots allowing a sufficient ATP production and an efficient suppression of toxic acetaldehyde formation in the early re-aeration period.
Assuntos
Etanol/metabolismo , Oryza/metabolismo , Brotos de Planta/metabolismo , Plântula/metabolismo , Triticum/metabolismo , Acetaldeído/metabolismo , Anaerobiose , Metabolismo dos Carboidratos/efeitos da radiação , Escuridão , Fermentação/efeitos da radiação , Glicólise/efeitos da radiação , Oryza/efeitos da radiação , Raízes de Plantas/metabolismo , Raízes de Plantas/efeitos da radiação , Brotos de Planta/efeitos da radiação , Plântula/efeitos da radiação , Triticum/efeitos da radiaçãoRESUMO
Low oxygen stress in plants can occur during flooding and compromise the availability and utilization of carbohydrates in root and shoot tissues. Low-oxygen-tolerant rice and -sensitive wheat plants were analyzed under anaerobiosis in light to evaluate main factors of the primary metabolism that affect sensitivity against oxygen deprivation: activity of glycolysis and the rate of photosynthesis. Relatively stable ATP contents (93 and 58% of aerated control levels after 24 h anaerobiosis) in illuminated shoot tissues account for enhanced tolerance of rice and wheat seedlings to anaerobiosis upon light exposure in comparison to anoxia in darkness. Although the photosynthetic process was inhibited during low oxygen stress, which was partly due to CO(2) deficiency, more light-exposed than dark-incubated seedlings survived. Illuminated plants could tolerate a 70% lower anaerobic ethanol production in shoots in comparison to darkness, although still an 18-times higher ethanol production rate was determined in rice than in wheat leaves. In conclusion, light-exposed plants grown under anaerobiosis may recycle low amounts of generated oxygen between photosynthesis and dissimilation and generate additional energy not only from substrate phosphorylation during glycolysis but also from other sources like cyclic electron transport.