RESUMO
OBJECTIVE: This study focused on the development of a new-to-world ingredient harnessing the natural potential of fresh Jasminum grandiflorum flowers to self-ferment by its phytobiome revealing flower content. Analytical investigations were conducted to highlight specific phytocompounds generated during the natural fermentation of flowers in comparison to a conventional extraction. The synergy with another extraction technology maximized the generation of biocompounds for an interesting efficacy. METHODS: Jasmine extract was elaborated by combining two patented technologies: the phytofermentology™, inspired by plant-microorganisms interaction and designed to develop ingredients obtained by natural fermentation of the vegetal using its own phytobiota; and the PSR™ technology allowing the extraction of bioactive phytocompounds such as small RNAs from plants. RESULTS: Analytical investigations of Jasmine extract highlighted uniqueness and richness of the phytocompound profiles, such as organics acids and phenolic compounds, markers of fermentation only obtained after phytofermentology in comparison to conventional extraction. Jasmine extract has the particularity to contain jasmintides, flower small peptides belonging to the family of cysteine-rich peptides (CRPs). Antioxidant and global anti-ageing properties were investigated in cell-free assays demonstrating interesting results: about 20% scavenging of free radicals from 0.5% of Jasmine extract and protection from DNA damage of 26% in comparison to a stressed control. CONCLUSION: Phytofermentology™ technology combined with PSR™ technology, meant to be respectful of the environment, allowed to development of biofunctionals very close to nature with a unique analytical signature as Jasmine extract, using the potential of fresh flowers phytobiota to self-ferment. The efficacy of the ingredient on global antioxidation and anti-ageing via hyaluronidase/tyrosinase inhibitions was highlighted by cell-free evaluation assays. Further and complementary studies should be conducted to confirm the bioefficacy of this ingredient with in vitro / ex vivo assays.
Cette étude a pour objectif de développer un nouvel ingrédient unique en exploitant le potentiel des fleurs fraîches de Jasminum grandiflorum à fermenter naturellement en utilisant leur phytobiome, révélant ainsi le contenu de ces fleurs. Des investigations analytiques ont été menées pour mettre en évidence des phytocomposés spécifiques générés lors de la fermentation naturelle des fleurs par rapport à une extraction conventionnelle. La synergie avec une autre technologie d'extraction maximise la génération de biocomposés pour une plus grande efficacité de l'extrait. L'extrait de jasmin a été élaboré en combinant deux technologies brevetées: la phytofermentologie™, inspirée de l'interaction plante/microorganismes et conçue pour développer des ingrédients obtenus par fermentation naturelle d'un végétal en utilisant son propre phytobiote; et la technologie PSR™ permettant l'extraction de phytocomposés bioactifs tels que les petits ARN des plantes. Les recherches analytiques de l'extrait de jasmin ont mis en évidence le caractère unique et la richesse des profils des différents phytocomposés composant l'extrait, tels que les acides organiques et les composés phénoliques, marqueurs de fermentation obtenus uniquement grâce à la phytofermentologie par rapport à l'extraction conventionnelle. L'extrait de jasmin a la particularité de contenir des jasmintides, petits peptides de fleurs appartenant à la famille des peptides riches en cystéine (CRP). Les propriétés antioxydantes et antiâge ont été étudiées par des tests acellulaires démontrant des résultats intéressants: environ 20 % d'élimination des radicaux libres à partir de 0,5 % d'extrait de jasmin et une protection contre les dommages à l'ADN de 26 % par rapport à un contrôle stressé. La technologie phytofermentologie™ combinée à la technologie PSR™, se voulant respectueuse de l'environnement, a permis de développer des ingrédients très proches de la nature avec une signature analytique unique comme l'extrait de Jasmin, utilisant le potentiel d'autofermentation du phytobiote des fleurs fraîches. L'efficacité de l'ingrédient sur l'antioxydation globale et l'antiâge via les inhibitions enzymatiques de la hyaluronidase et de la tyrosinase a été mise en évidence par des tests d'évaluation acellulaires. Des études supplémentaires et complémentaires devraient être menées pour confirmer la bioefficacité de cet ingrédient avec des tests in vitro/ex vivo.
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Nerve growth factor (NGF), a critical mediator of nociception, is a novel analgesic therapeutic target. Bedinvetmab, a canine monoclonal antibody (mAb), binds NGF and inhibits its interaction with tropomyosin receptor kinase A (trkA) and p75 neurotrophin receptor (p75NTR) receptors. The objective of three integrated laboratory studies was to demonstrate the safety of bedinvetmab in adult laboratory Beagle dogs. Daily health, veterinary, clinical pathology, systemic exposure, and anti-drug antibody evaluations were performed. Study 1 additionally included electrocardiography, neurologic, and ophthalmic assessments, and radiographic monitoring of joints of the appendicular skeleton. Study 2 evaluated T-lymphocyte-dependent immune function. Study 3 evaluated the safety of short-term concurrent administration of carprofen, a nonsteroidal anti-inflammatory drug (NSAID), with bedinvetmab. Studies 1 and 3 included terminal pathology and histopathology evaluations. Study designs and procedures included directed complementary morphologic and functional evaluations of a literature- and in vitro-based list of potential safety issues related to the NGF signaling pathway and characteristics engineered into this mAb. Screening-level general procedures evaluated effects associated with mAbs that target and inhibit soluble agonist cytokines. There were no treatment-related adverse changes in clinical evaluations, clinical neurological and ophthalmic examinations, joints, immune morphology or function, and no effects of short-term concurrent NSAID usage. Treatment-emergent immunogenicity was not observed. Bedinvetmab (1 mg/kg SC monthly; 3× and 10× dose multiples) was well tolerated in normal laboratory Beagle dogs for 6 months and with 2 weeks' concurrent NSAID administration.
Assuntos
Laboratórios , Fator de Crescimento Neural , Animais , Anticorpos Monoclonais/efeitos adversos , Cães , Receptor de Fator de Crescimento Neural , Transdução de SinaisRESUMO
Skin-derived precursors (SKPs) have been described as multipotent dermal precursors. Here, we provide a review of the breadth and depth of scientific literature and studies regarding SKPs, accounting for a large number of scientific publications. Interestingly, these progenitors can be isolated from embryonic and adult skin, as well as from a population of dermal cells cultured in vitro in monolayer. Gathering information from different authors, this review explores different aspects of the SKP theme, such as the potential distinct origins of SKPs in rodents and in humans, and also their ability to differentiate in vitro and in vivo into multiple lineages of different progeny. This remarkable capacity makes SKPs an interesting endogenous source of precursors to explore in the framework of experimental and therapeutic applications in different domains. SKPs are not only involved in the skin's dermal maintenance and support as well as wound healing, but also in hair follicle morphogenesis. This review points out the interests of future researches on SKPs for innovative perspectives that may be helpful in many different types of scientific and medical domains.
Les cellules souches précurseurs dérivées de la peau (nommées SKPs) ont été décrites comme des progéniteurs dermiques multipotents. La présente revue permet d'avoir une vue d'ensemble des études et travaux portant sur le thème des SKPs, regroupant un nombre important de publications scientifiques. Il est intéressant de noter que ces cellules progénitrices peuvent être isolées de la peau embryonnaire et adulte, ainsi que d'une population de cellules dermiques cultivées in vitro en monocouche. Réunissant les travaux de plusieurs auteurs, cette revue explore différents thèmes autour des SKPs, tels que leur origine chez les rongeurs et chez l'homme ; mais aussi, leur capacité à se différencier in vitro et in vivo en un grand nombre de lignées cellulaires de descendances différentes. Cette capacité fondamentale des SKPs en fait une source de précurseurs endogènes intéressante à explorer dans le cadre d'applications expérimentales et thérapeutiques dans différents domaines. Les SKPs participent non seulement à l'homéostasie, au maintien du derme, mais aussi à la cicatrisation des plaies et à la morphogenèse du follicule pileux. Cette revue souligne l'intérêt des expérimentations en cours et à venir concernant les SKPs en vue de perspectives innovantes pouvant influencer la recherche dans de nombreux domaines scientifiques et médicaux.
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Regeneração , Pele , Animais , Humanos , Roedores , Células-Tronco/citologia , CicatrizaçãoRESUMO
BACKGROUND: Self-explanation without feedback has been shown to improve medical students' diagnostic reasoning. While feedback is generally seen as beneficial for learning, available evidence of the value of its combination with self-explanation is conflicting. This study investigated the effect on medical students' diagnostic performance of adding immediate or delayed content-feedback to self-explanation while solving cases. METHODS: Ninety-four 3rd-year students from a Canadian medical school were randomly assigned to three experimental conditions (immediate-feedback, delayed-feedback, control). In the learning phase, all students solved four clinical cases by giving i) the most likely diagnosis, ii) two main arguments supporting this diagnosis, and iii) two plausible alternative diagnoses, while using self-explanation. The immediate-feedback group was given the correct diagnosis after each case; delayed-feedback group received the correct diagnoses only after the four cases; control group received no feedback. One week later, all students solved four near-transfer (i.e., same final diagnosis as the learning cases but different scenarios) and four far-transfer cases (i.e., different final diagnosis from the learning cases and different scenarios) by answering the same three questions. Students' diagnostic accuracy (score for the response to the first question only) and diagnostic performance (combined score of responses to the three questions) scores were assessed in each phase. Four one-way ANOVAs were performed on each of the two scores for near and far-transfer cases. RESULTS: There was a significant effect of experimental condition on diagnostic accuracy on near-transfer cases (p < .05). The immediate-feedback and delayed-feedback groups performed equally well, both better than control (respectively, mean = 90.73, standard deviation =10.69; mean = 89.92, standard deviation = 13.85; mean = 82.03, standard deviation = 17.66). The experimental conditions did not significantly differ on far-transfer cases. CONCLUSIONS: Providing feedback to students in the form of the correct diagnosis after using self-explanation with clinical cases is potentially beneficial to improve their diagnostic accuracy but this effect is limited to similar cases. Further studies should explore how more elaborated feedback combined with self-explanation may impact students' diagnostic performance on different cases.
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Diagnóstico , Educação Médica/métodos , Feedback Formativo , Estudantes de Medicina , Competência Clínica , Feminino , Humanos , Masculino , Estudantes de Medicina/psicologia , Inquéritos e Questionários , Adulto JovemRESUMO
A minimum data set consisting of 15 data elements originating from laboratory submissions and results was formulated by a national committee of epidemiologists in Canada for the purposes of disease reporting, disease detection and analysis. The data set consists of both data that are filled out on the submission form as well as the results of the laboratory testing. The elements in the data set are unique identifier, premises identification, date submitted, geographic location, species, farm type, group type, total population of tested species on the farm, number sick, number dead, test(s) performed, disease agent, test result, disease classification by submitter and final laboratory diagnosis. The data set was designed to be concise while allowing for domestic and international disease reporting, effective analysis, including geographic, temporal and prevalence outputs, and syndromic surveillance to enable disease detection. The selected data elements do not identify the producer as specific geographic and nominal information is not included in the data set. The data elements selected, thus, allow for voluntary collaboration and data sharing by avoiding issues associated with privacy legislation.
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Doenças dos Animais/epidemiologia , Surtos de Doenças/veterinária , Laboratórios/estatística & dados numéricos , Vigilância de Evento Sentinela/veterinária , Animais , Canadá/epidemiologia , Controle de Doenças Transmissíveis/métodos , Surtos de Doenças/prevenção & controle , Gado , Vigilância da População , Prática de Saúde PúblicaRESUMO
The stem cell factor (SCF) and its protein-tyrosine kinase receptor KIT are together implicated in the regulation of diverse biological processes and particularly in melanogenesis. Indeed, this signalling pathway controls melanoblast migration from the neural crest during embryogenesis and allows the communication between keratinocytes and melanocytes in the adult. In melanocytes, the binding of SCF to its transmembrane receptor leads to the activation of signalling pathways implicating protein kinases which finally control the expression of pigmentation-related genes. We have developed a biological compound called IV09.007, which we previously described as a modulator of the SCF/KIT signalling pathway with a pro-pigmenting effect. In the present work, we have studied the expression and localization of both SCF and KIT mRNAs and proteins in the skin or skin-derived cell lines. Then, we explored with a microarray approach the ability of IV09.007 to modulate the expression of genes in human keratinocytes and melanocytes in culture. Thereby, we observed the regulation of genes implicated in DNA repair, mainly related to base/nucleotides excision pathways. A modulated transcriptional response was also observed for some genes implicated in the response against oxidative stress, in apoptosis inhibition and in lowering inflammatory immune response. These microarray results predicted a conferred protective effect of IV09.007 and we verified this hypothesis by performing comet assays on UVB-irradiated keratinocytes or melanocytes, to demonstrate the efficacy of IV09.007 on preventing DNA damage.
Assuntos
Dano ao DNA , Perfilação da Expressão Gênica , Queratinócitos/efeitos da radiação , Proteínas Proto-Oncogênicas c-kit/metabolismo , Transdução de Sinais , Fator de Células-Tronco/metabolismo , Raios Ultravioleta , Adulto , Linhagem Celular , Feminino , Humanos , Queratinócitos/metabolismo , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo RealRESUMO
There is growing interest in developing tools and methods for the surveillance of chronic rheumatic diseases, using existing resources such as administrative health databases. To illustrate how this might work, we used population-based administrative data to estimate and compare the prevalence of systemic autoimmune rheumatic diseases (SARDs) across three Canadian provinces, assessing for regional differences and the effects of demographic factors. Cases of SARDs (systemic lupus erythematosus, scleroderma, primary Sjogren's, polymyositis/dermatomyositis) were ascertained from provincial physician billing and hospitalization data. We combined information from three case definitions, using hierarchical Bayesian latent class regression models that account for the imperfect nature of each case definition. Using methods that account for the imperfect nature of both billing and hospitalization databases, we estimated the over-all prevalence of SARDs to be approximately 2-3 cases per 1,000 residents. Stratified prevalence estimates suggested similar demographic trends across provinces (i.e. greater prevalence in females-versus-males, and in persons of older age). The prevalence in older females approached or exceeded 1 in 100, which may reflect the high burden of primary Sjogren's syndrome in this group. Adjusting for demographics, there was a greater prevalence in urban-versus-rural settings. In our work, prevalence estimates had good face validity and provided useful information about potential regional and demographic variations. Our results suggest that surveillance of some rheumatic diseases using administrative data may indeed be feasible. Our work highlights the usefulness of using multiple data sources, adjusting for the error in each.
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Doenças Autoimunes/epidemiologia , Doenças Reumáticas/epidemiologia , Adulto , Idoso , Canadá/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
BACKGROUND: A facial contour that is oval is more pleasing in Asian women. Patients with a square face often seek facial contouring procedures to improve their appearance. Treatment often involves various combinations of Botulinum NeuroToxin A (BoNTA) injections into the masseters and/or mandibular angle resection. Many physicians claim that muscle paralysis with injections alone will decrease pulling on the underlying bone and also treat underlying bony flaring when present. Muscular changes after BoNTA injections have been well documented. However, the effect of BoNTA injections on the underlying mandibular bone morphology has not been studied to the best of the authors' knowledge. The goal of this study was to determine whether there are mandibular changes after masseter injection with botulinum toxin. METHODS: In this retrospective study of ten female patients seeking treatment for a square face, three-dimensional CT scans were taken before and 3 months after standardized BoNTA injections in bilateral masseters. Mandibular cortex thickness, mandibular bone thickness, and mandibular volume were measured. RESULTS: Soft-tissue changes were observed but no bony changes were observed 3 months after injections. CONCLUSIONS: In this study of adult patients, there were no statistically significant mandibular changes 3 months after BoNTA injection. The current theory of mandibular flaring resolution after partial muscle paralysis is not supported by our findings. Therefore, a patient presenting both masseteric hypertrophy and bony flaring will most likely require a combined muscular and bony procedure.
Assuntos
Toxinas Botulínicas Tipo A/farmacologia , Mandíbula/efeitos dos fármacos , Mandíbula/diagnóstico por imagem , Fármacos Neuromusculares/farmacologia , Adulto , Povo Asiático , Técnicas Cosméticas , Face , Feminino , Humanos , Hipertrofia , Injeções Intramusculares , Músculo Masseter/efeitos dos fármacos , Músculo Masseter/patologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
Median cleft lip is a rare congenital anomaly. The wide diastema with mesial tipping observed in these patients has been largely overlooked. A midline submucosal alveolar cleft prevents adequate treatment. The purpose of this article is to describe an alveolar bone grafting (ABG) technique used in the combined surgical-orthodontic approach to diastema treatment in patients presenting with incomplete median cleft lip. Patients treated for incomplete median cleft lip and diastema were identified in the clinic registry from 1981 to 2007. Six patients were identified; 4 underwent ABG before permanent maxillary incisor eruption, the other 2 were seen later when they were 11 years old. All 6 ABGs were successful. The incisors erupted through the graft or were successfully moved into it with lasting results. Follow-up ranged from 8 to 21 years. The existence of a midline submucosal alveolar cleft and subsequent diastema should be recognized and addressed in all patients who present with incomplete median cleft lip repair. This includes taking maxillary occlusal view X-rays before the age of 5 years to detect the cleft, and proceed to ABG if necessary, generally before permanent maxillary incisor eruption.
Assuntos
Processo Alveolar/anormalidades , Alveoloplastia/métodos , Transplante Ósseo/métodos , Fenda Labial/cirurgia , Diastema/cirurgia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Incisivo/fisiologia , Masculino , Maxila/anormalidades , Maxila/cirurgia , Contenções Ortodônticas , Estudos Retrospectivos , Retalhos Cirúrgicos , Coleta de Tecidos e Órgãos/métodos , Erupção Dentária/fisiologia , Técnicas de Movimentação Dentária/instrumentação , Resultado do TratamentoRESUMO
This article explores the principle of self-determination as it relates to victims of elder abuse and neglect. Using newspaper accounts and cases from the author's practice and consulting files, various factors influencing the professional's interpretation of this principle are explored. The notion that self-determination allows victims of abuse and neglect to refuse intervention is challenged. The author concludes that the principle of self-determination and the notion of competency are overly simplified in the social work and elder abuse literature and may be misused by allowing abused older victims to choose to remain in often life-threatening situations. Special focus is given to Adult Protection Service worker, but the author asserts that protecting older people, assisting in creative interventions and developing needed services is a shared professional responsibility.
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Tomada de Decisões , Abuso de Idosos/prevenção & controle , Avaliação Geriátrica , Serviços de Saúde para Idosos/normas , Autonomia Pessoal , Serviço Social/normas , Idoso , Idoso de 80 Anos ou mais , Competência Clínica , Humanos , Notificação de Abuso , Competência Mental , Responsabilidade Social , Estados UnidosRESUMO
Elder abuse reporting laws exist in every state to protect elderly people being abused physically or emotionally, suffering from neglect, or experiencing financial exploitation. Support groups for caregivers of elderly individuals may help prevent elder abuse by reducing caregiver stress and linking caregivers to community services. Using case illustrations, the authors raise the dilemmas that group facilitators face when deciding whether to report a group member suspected of abusing his or her elder care recipient. The ethical concerns of reporting or withholding a report are discussed, and recommendations to assist facilitators in this complex decision process are presented.
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Cuidadores/psicologia , Abuso de Idosos/legislação & jurisprudência , Notificação de Abuso/ética , Serviço Social/ética , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Apoio SocialRESUMO
We report 4 cases of hepatic injury in patients treated with a dextropropoxyphene-paracetamol combination in which the causal relationship with dextropropoxyphene can be suspected. These four cases show similarities with the 29 cases found in international publications. Hepatotoxicity occurs more frequently among old patients and women. Clinically, this condition can mimic a biliary tract disease with sometimes few or no symptoms. Biochemical criteria can show cholestatic, mixed or cytolytic hepatitis. Intrahepatic cholestasis may be found in liver biopsies sometimes suggesting cholangitis. Outcome is favourable on withdrawal of the drug. The mechanism of action of dextropropoxyphene is discussed.
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Analgésicos Opioides/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Dextropropoxifeno/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , HumanosRESUMO
It is well established that programmed cell death claims up to two-thirds of the oocytes produced during gametogenesis in the developing fetal ovaries. However, the mechanisms underlying prenatal germ cell loss in females remain poorly understood. Herein we report that caspase-11 null female mice are born with a reduced number of oocyte-containing primordial follicles. This phenotype is likely due to failed cytokine processing known to occur in caspase-11 mutants since neonatal female mice lacking both interleukin (IL)-1alpha and IL-1beta also exhibit a reduced endowment of primordial follicles. In addition, germ cell death in wild-type fetal ovaries cultured ex vivo is suppressed by either cytokine, likely via ligand activation of type 1 IL-1 receptors expressed in fetal germ cells. Normal oocyte endowment can be restored in caspase-11 null female mice by simultaneous inactivation of the gene encoding the cell death executioner enzyme, caspase-2. However, caspase-2 deficiency cannot overcome gametogenic failure resulting from meiotic recombination defects in ataxia telangiectasia-mutated (Atm) null female mice. Thus, genetically distinct mechanisms exist for developmental deletion of oocytes via programmed cell death, one of which probably functions as a meiotic quality-control checkpoint that cannot be overridden.
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Apoptose/genética , Caspases/deficiência , Citocinas/deficiência , Meiose/genética , Oócitos/citologia , Oócitos/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas c-bcl-2 , Animais , Apoptose/efeitos dos fármacos , Proteínas Mutadas de Ataxia Telangiectasia , Caspase 1/metabolismo , Caspase 10 , Caspase 2 , Caspases/genética , Caspases/metabolismo , Caspases Iniciadoras , Proteínas de Ciclo Celular , Citocinas/genética , Citocinas/farmacologia , Proteínas de Ligação a DNA , Feminino , Deleção de Genes , Interleucina-1/metabolismo , Interleucina-1/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Oócitos/enzimologia , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Supressoras de Tumor , Proteína X Associada a bcl-2RESUMO
The ability of Actinomyces naeslundii to convert sucrose to extracellular homopolymers of fructose and to catabolize these types of polymers is suspected to be a virulence trait that contributes to the initiation and progression of dental caries and periodontal diseases. Previously, we reported on the isolation and characterization of the gene, ftf, encoding the fructosyltransferase (FTF) of A. naeslundii WVU45. Allelic exchange mutagenesis was used to inactivate ftf, revealing that FTF-deficient stains were completely devoid of the capacity to produce levan-type (beta2,6-linked) polysaccharides. A polyclonal antibody was raised to a histidine-tagged, purified A. naeslundii FTF, and the antibody was used to localize the enzyme in the supernatant fluid. A sensitive technique was developed to detect levan formation by proteins that had been separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the method was used to confirm that the levan-synthesizing activity of A. naeslundii existed predominantly in a cell-free form, that a small amount of the activity was cell associated, and that the ftf mutant was unable to produce levans. By using the nucleotide sequence of the levanase gene of a genospecies 2 A. naeslundii, formerly Actinomyces viscosus, a portion of a homologue of this gene (levJ) was amplified by PCR and inserted into a suicide vector, and the resulting construct was used to inactivate the levJ gene in the genospecies 1 strain WVU45. A variety of physiologic and biochemical studies were performed on the wild-type and LevJ-deficient strains to demonstrate that (i) this enzyme was the dominant levanase and sucrase of A. naeslundii; (ii) that LevJ was inducible by growth in sucrose; (iii) that the LevJ activity was found predominantly (>90%) in a cell-associated form; and (iv) that there was a second, fructose-inducible fructan hydrolase activity produced by these strains. The data provide the first detailed molecular analysis of fructan production and catabolism in this abundant and important oral bacterium.
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Actinomyces/enzimologia , Proteínas de Bactérias , Frutanos/metabolismo , Glicosídeo Hidrolases/metabolismo , Hexosiltransferases/metabolismo , Sacarase/metabolismo , Sacarose/metabolismo , Actinomyces/crescimento & desenvolvimento , Meios de Cultura , Eletroforese em Gel de Poliacrilamida , Regulação Bacteriana da Expressão Gênica , Glicosídeo Hidrolases/genética , Hexosiltransferases/genética , Humanos , Sacarase/genéticaRESUMO
BACKGROUND: The linearity of cisatracurium elimination and its concentration-effect relation were determined as part of a traditional rich data study with three dose levels in patients receiving balanced anesthesia. METHODS: Forty-eight adults with American Society of Anesthesiologists status I-II were randomized to receive an intravenous bolus dose of 0.075, 0.15, or 0.30 mg/kg cisatracurium. Anesthesia was induced and maintained with nitrous oxide-oxygen, propofol, and fentanyl. The mechanical response of the adductor pollicis muscle was recorded. Arterial blood samples were collected over 8 h. Cisatracurium, laudanosine, and the monoquaternary alcohol concentrations were measured by high-performance liquid chromatography. To assess the relative contribution of the input function, a parametric (assuming elimination from both the central and peripheral compartments) and a nonparametric pharmacokinetic-pharmacodynamic model were both applied to data. RESULTS: Dose proportionality of the body disposition of cisatracurium and its two major metabolites at doses up to 0.30 mg/kg was confirmed. With the parametric approach, the effect compartment concentration at 50% block (EC50) significantly increased with the dose (136 vs. 157 vs. 209 ng/ml), whereas the effect compartment equilibration rate constant decreased (0.0675 vs. 0.0568 vs. 0.0478 min(-1)). A similar dose-dependent effect of the pharmacokinetic-pharmacodynamic relation was observed with the nonparametric approach, but the trend was 50% less pronounced. CONCLUSION: A dose-related change in pharmacokinetic-pharmacodynamic parameters was identified with both modeling approaches. A pharmacokinetic origin was ruled out, although no definite explanation of the underlying mechanism could be provided. These findings suggest that doses relevant to the anesthetic practice be used for estimation of EC50.
Assuntos
Anestesia , Atracúrio/farmacologia , Fármacos Neuromusculares não Despolarizantes/farmacologia , Adolescente , Adulto , Idoso , Algoritmos , Área Sob a Curva , Atracúrio/administração & dosagem , Atracúrio/farmacocinética , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Monitorização Intraoperatória , Fármacos Neuromusculares não Despolarizantes/administração & dosagem , Fármacos Neuromusculares não Despolarizantes/farmacocinéticaRESUMO
PURPOSE: To document the clinical characteristics of spinal procaine with or without the addition of fentanyl in light of the failure rate observed previously with procaine 10%. METHODS: In a randomized, prospective, double-blind study, 52 patients received spinal anesthesia with 100 mg procaine and either saline 0.9% (0.4 ml) (CONTROL group) or 20 microg fentanyl (0.4 ml) (FENTANYL group). Sensory anesthesia to needle prick was evaluated each minute for ten minutes, every three minutes for 33 minutes and every five minutes until regression to T10. Motor block was assessed with the Bromage scale. Patients were questioned by telephone for pain suggesting transient radicular irritation (TRI) 48 hr later. RESULTS: Mean time to reach highest sensory level, maximum number of segments blocked and mean time for regression of the sensory level to T10 showed no difference. Time to recuperate to full flexion of knees and feet (Bromage 4) showed no difference. Nine patients had nausea (five in CONTROL group and four in FENTANYL group) and nine had pruritus (three in CONTROL group and six in FENTANYL group). No patient reported pain suggesting TRI. CONCLUSION: Spinal procaine is appropriate for short-duration surgery. Fentanyl does not change the characteristics of the block or the incidence of side effects associated with spinal procaine.
Assuntos
Analgésicos Opioides , Raquianestesia , Anestésicos Locais , Fentanila , Procaína , Adolescente , Adulto , Idoso , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Raquianestesia/efeitos adversos , Anestésicos Locais/efeitos adversos , Dor nas Costas/induzido quimicamente , Pressão Sanguínea/efeitos dos fármacos , Método Duplo-Cego , Feminino , Fentanila/administração & dosagem , Fentanila/efeitos adversos , Humanos , Injeções Espinhais , Masculino , Pessoa de Meia-Idade , Medição da Dor , Procaína/efeitos adversos , Estudos Prospectivos , Fatores de TempoRESUMO
PURPOSE: To compare spinal procaine to spinal lidocaine with regard to their main clinical characteristics and incidence of transient radicular irritation (TRI). METHODS: In this randomized, double-blind, prospective study, patients (two groups, n=30 each) received either 100 mg of lidocaine 5% in 7.5% glucose (Group L) or 100 mg of procaine 10% diluted with 1 ml cerebrospinal fluid (Group P). After spinal anesthesia, segmental level of sensory block was assessed by pinprick. Blood pressure and the height of the block were noted each minute for the first ten minutes, then every three minutes for the next 35 min and finally every five minutes until regression of the block to L4. Motor blockade was evaluated using the Bromage scale. To evaluate the presence of TRI, each patient was questioned 48 hr after surgery. RESULTS: Time to highest sensory level and to maximum number of segments blocked showed no difference between groups. Mean time for sensory regression to T10 and for regression of the motor block were shorter in Group P. Eighty minutes following injection, sensory levels were lower in Group P. Five patients had inadequate surgical anesthesia in Group P and only one in Group L. No patient in Group P had TRI (95% CI 10-12%) while eight (27%) in Group L did (95% CI 12-46%). CONCLUSIONS: Procaine 10% was associated with a clinical failure rate of 14.2%. This characteristic must be balanced against an absence of TRI, which occurs more frequently with the use of lidocaine 5%.
Assuntos
Raquianestesia , Anestésicos Locais , Lidocaína , Procaína , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Estudos Prospectivos , Fatores de TempoRESUMO
Oral actinomycetes produce fructosyltransferase (FTF) enzymes which convert sucrose into polymers of D-fructose, known as levans, and these polymers are thought to contribute to the persistence and virulence of the organisms. A gene encoding FTF was isolated from Actinomyces naeslundii WVU45; the deduced amino acid sequence showed significant similarity to known levansucrases of gram-negative environmental isolates but was less similar to FTFs from gram-positive bacteria. A transcriptional start site was mapped by primer extension 70 bp 5' from the putative start codon. Promoter fusions to a chloramphenicol acetyltransferase gene were used to confirm that there was a functional promoter driving ftf expression and to show that sequences located 86 to 218 bp upstream of the transcription initiation site were required for optimal ftf expression. Quantitative slot blot analysis against total RNA from cells grown on different sugars or from different growth phases revealed that ftf was constitutively transcribed. Thus, the A. naeslundii FTF is more similar in primary sequence and the regulation of expression to levansucrases of gram-negative bacteria than gram-positive bacteria.
Assuntos
Actinomyces/enzimologia , Genes Bacterianos , Hexosiltransferases/genética , Actinomyces/genética , Sequência de Aminoácidos , Sítios de Ligação , Cloranfenicol O-Acetiltransferase/metabolismo , Mapeamento Cromossômico , Regulação Bacteriana da Expressão Gênica , Regulação Enzimológica da Expressão Gênica , Hexosiltransferases/metabolismo , Dados de Sequência Molecular , Regiões Promotoras Genéticas , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Homologia de Sequência de Aminoácidos , Transcrição GênicaRESUMO
Previous epidemiological studies of correlates of child and adolescent mental disorders in the general population have focused more on child/adolescent and socioeconomic/sociodemographic characteristics than on family characteristics. Moreover, there are no generally accepted methods to analyze and interpret correlates. The purpose of the Quebec Child Mental Health Survey in this regard was twofold: (1) to identify correlates of DSM-III-R internalizing and externalizing disorders according to informant (youth, parent, teacher), for three age groups (6-8, 9-11, and 12-14 years), including relevant family characteristics not considered in previous studies; and (2) to interpret the relative importance of risk indicators by ranking correlates according to strength and consistency of association across age groups. Logistic regression models suggest the inconsistency of correlates across informants. The ranking of correlates reveals that individual and family characteristics make a more important contribution than do socioeconomic characteristics, thereby supporting the relevance of proximal variables in the development of psychopathology.
Assuntos
Transtornos Mentais/epidemiologia , Adolescente , Comportamento do Adolescente/psicologia , Fatores Etários , Criança , Feminino , Humanos , Masculino , Transtornos Mentais/diagnóstico , Vigilância da População , Escalas de Graduação Psiquiátrica , Psicologia do Adolescente , Quebeque/epidemiologia , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: To review the Dominic-R and the Terry questionnaires, respectively, for white and African-American children, both DSM-III-R-based, and more recent DSM-IV-based computerized versions. METHOD: Five papers describing the development, content, validation studies, and establishment of the diagnostic cutpoints of these instruments are reviewed. The instruments are pictorial, fully structured, and designed to assess mental disorders in children 6 to 11 years of age. Symptom descriptions complement the visual stimulus, providing better information-processing than visual or auditory stimuli alone. Cognitive immaturity of young children bars frequency, duration, and age-of-onset measurements, restricting correspondence with DSM criteria. DSM-IV (computerized versions) and DSM-III-R (paper versions) disorders being assessed include specific (simple) phobias, separation anxiety, generalized anxiety (overanxious), depression/dysthymia, attention-deficit hyperactivity, oppositional defiant, and conduct disorder. RESULTS: Test-retest reliability of symptoms and symptom scores and criterion validity against clinical judgment support the visual-auditory combination of stimuli to assess child mental health. CONCLUSION: Intended for clinical, epidemiological, and screening purposes, these instruments are short and simple. Although it only approximates DSM-III-R and DSM-IV criteria, the pictorial format permits young children to be reliable informants about their mental health.