RESUMO
BACKGROUND AND PURPOSE: We aimed to test the clinical utility of the leg:thigh intraepidermal nerve-fiber (IENF) density ratio as a parameter to discriminate between length-dependent small-fiber neuropathy (SFN) and small-fiber sensory ganglionopathy (SFSG) in subjects with signs and symptoms of small-fiber pathology. METHODS: We retrospectively evaluated thigh and leg IENF density in 314 subjects with small-fiber pathology (173 with distal symmetrical length-dependent SFN and 141 with non-length-dependent SFSG). A group of 288 healthy subjects was included as a control group. The leg:thigh IENF density ratio was calculated for all subjects. We used receiver operating characteristic curve analyses to assess the ability of this parameter to discriminate between length-dependent SFN and SFSG, and the decision curve analysis to estimate its net clinical benefit. RESULTS: In patients with neuropathy, the mean IENF density was 14.8 ± 6.8/mm at the thigh (14.0 ± 6.9/mm in length-dependent SFN and 15.9 ± 6.7/mm in patients with SFSG) and 7.5 ± 4.5/mm at the distal leg (5.4 ± 3.2/mm in patients with length-dependent SFN and 10.1 ± 4.6/mm in patients with SFSG). The leg:thigh IENF density ratio was significantly (P < 0.01) lower in patients with length-dependent SFN (0.44 ± 0.23) compared with patients with SFSG (0.68 ± 0.28). The area under the curve of the receiver operating characteristic analysis to discriminate between patients with length-dependent SFN and SFSG was 0.79. The decision curve analysis demonstrated the clinical utility of this parameter. CONCLUSIONS: The leg:thigh IENF ratio represents a valuable tool in the differential diagnosis between SFSG and length-dependent SFN.
Assuntos
Fibras Nervosas/patologia , Doenças do Sistema Nervoso Periférico/diagnóstico , Pele/patologia , Neuropatia de Pequenas Fibras/diagnóstico , Adulto , Idoso , Biópsia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso Periférico/patologia , Estudos Retrospectivos , Neuropatia de Pequenas Fibras/patologiaRESUMO
Balclutha brevis Lindberg 1954 (Homoptera, Cicadellidae) is an allochthonous species that is rapidly spreading in Sicily and in mainland Europe due to the wide spread of its host plant and therefore could also compete with populations of native species. Considering these ecological implications, based on the lacking ultrastructural data about the reproductive systems of the Auchenorrhyncha and since previous investigations on the male reproductive system of B. brevis have shown some interesting features, we carried out morphostructural investigations on the female reproductive system of this alien leafhopper. Moreover, given the high interest in literature on Wolbachia entomoparasite and based on our previous studies, we provided a contribution to further investigations in applied sciences. For this aim we performed a molecular analysis on males and females of B. brevis to detect the possible presence of strains of the bacterium known to alter host reproductive biology. The female reproductive system has a morphological organization comparable to the general anatomical features of most of the Auchenorrhyncha species; however, comparing our data with the literature, some considerations are discussed. As for the histological and ultrastructural investigations, our results show a secretory activity of the various examined structures. In the spermatheca of B. brevis, in particular, the secretory activity is more marked in the sac-shaped tract, where histochemical investigations showed a lipid component of the secretion; possible origin of this component is discussed. Moreover, mainly free spermatozoa are found in the sac-shaped tract of the spermatheca and in the common oviduct. As for the latter, an interesting findings is the lack of cuticular intima on the epithelial surface of the common oviduct; furthermore, the observed features and the literature in this regards led us to review the significance of the structure called as spermatheca. The molecular screening study (PCR) with three Wolbachia specific genes (16SrRNA, ftsZ,wsp) strongly supports Wolbachia infections in both males and females of the host species. This is the first study demonstrating the presence of Wolbachia in Balclutha genus, though no morphostructural alteration commonly related to the presence of the bacterium has been found in all the examined specimens.
Assuntos
Hemípteros/microbiologia , Wolbachia/isolamento & purificação , Animais , Proteínas de Bactérias/genética , DNA Bacteriano/análise , DNA Bacteriano/genética , DNA Ribossômico/genética , Europa (Continente) , Feminino , Genitália Feminina/anatomia & histologia , Genitália Feminina/ultraestrutura , Histocitoquímica , Masculino , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Dados de Sequência Molecular , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Wolbachia/classificação , Wolbachia/genéticaRESUMO
Photobiomodulation (PBM) can induce a set of different biological modulators either in vitro or in vivo. Experimental evidence has highlighted the role of light effects on the mechanisms related to inflammation, apoptosis and autophagy. The goal of this project was the evaluation of PBM on U937, an established cell line of histiocytic lymphoma origin. Several aspects of modulation of proinflammatory pathways were analyzed and autophagic and proapoptotic mechanisms related to low laser light exposure of cells were studied. As a source of low energy light emission, we used an NIR-LED device, characterized by an 880 nm-wavelength as light source. Flow cytometry analysis was performed on supernatants of controls and treated U937 cells to detect inflammatory cytokine levels. In order to evaluate NF-kB and caspase3 expressions, Western blot analysis was performed according to standard procedures. In this report, we show the effect of PBM on a monocyte/macrophage established tumor cell line (U-937). We demonstrate that LED exposure, in the presence or absence of lipopolysaccharide (LPS), activates cell degranulation, increased expression of Interleukin-8 (IL-8) and modulation of beta galactosidase activity. Evidence shows that the well-known pro-inflammatory nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and the apoptotic marker (caspase3/cleaved-caspase3 ratio) are up-regulated in response to a proinflammatory biochemical pathway.
Assuntos
Apoptose/efeitos da radiação , Degranulação Celular/efeitos da radiação , Terapia com Luz de Baixa Intensidade , Macrófagos/efeitos da radiação , Monócitos/efeitos da radiação , Western Blotting , Caspase 3/metabolismo , Citometria de Fluxo , Humanos , Inflamação/metabolismo , Interleucina-8/metabolismo , Macrófagos/metabolismo , Monócitos/metabolismo , NF-kappa B/metabolismo , Células U937RESUMO
BACKGROUND AND PURPOSE: Quantification of intraepidermal nerve fibers (IENFs) in skin biopsies is now the tool of choice to diagnose small fiber neuropathies. An adequate normative dataset, necessary to assess normality cutoffs, is available for brightfield microscopy but not for immunofluorescence. METHODS: Intraepidermal nerve fiber density data in distal leg skin samples processed with immunofluorescence were collected from 528 healthy individuals from four experienced laboratories worldwide. In all laboratories skin samples were collected, processed and analyzed according to standard procedures. Quantile regression analysis was employed to tailor the fit of the 5° percentile as the normal cutoff value and to test and measure the effect of age, gender, body mass index, race, biopsy site (lateral distal lower leg or medial posterior mid-calf) and participating laboratory as possible influential variables. RESULTS: Age, gender and biopsy site showed an independent linear correlation with IENF density. For each decade the 5° quantile IENF cutoff showed a 0.54 fibers/mm decrease, whilst females exhibited a 1.0 fiber/mm cutoff greater than males. Compared to the lateral distal lower leg, biopsies from the calf showed a 3.4 fibers/mm lower 5° percentile cutoff, documenting a variation linked by site. CONCLUSIONS: An age- and gender-adjusted normative dataset for IENF density at the lateral distal lower leg obtained with indirect immunofluorescence is presented for the first time by sharing data from four experienced laboratories worldwide. This dataset can be used as reference for laboratories processing skin biopsies with this technique.
Assuntos
Epiderme/inervação , Perna (Membro)/inervação , Fibras Nervosas , Adulto , Feminino , Imunofluorescência , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso Periférico/diagnóstico , Valores de ReferênciaRESUMO
Balclutha brevis Lindberg 1954 is an allochthonous leafhopper infesting an invasive grass, Pennisetum setaceum, in Sicily and in mainland Europe; therefore, this species could compete with populations of native species, thus contributing to the loss of biodiversity. Considering the ecological implications of B. brevis, investigations on all its biological aspects represent, therefore, a premise for further studies in applied sciences. Based on the lacking ultrastructural data about the reproductive systems of the Auchenorrhyncha, we carried out morphostructural investigations on the male reproductive system of B. brevis. Further, a first report of DNA barcoding analysis (amplification and sequencing of Cytochrome Oxidase I gene) has also been performed to characterize B. brevis compared to other congeneric species. From a morphological point of view, the male reproductive system of B. brevis has an organization comparable to the general anatomical features of most of the Auchenorrhyncha species; however, comparing our data with those concerning the different groups of Cicadomorpha, some considerations are discussed. As for the histological and ultrastructural investigations, our results show a secretory activity of the various examined structures, mainly in the lateral ejaculatory ducts and in the accessory glands. The latter, in particular, show morphostructural differences comparing the distal tract to the proximal one; moreover, the histochemical techniques showed the possible presence of a lipid component in the peculiar cytoplasmic granules found in the gland cells. The significance of these findings in the accessory glands is discussed. Finally, the ultrastructural features found in the seminal vesicles are different from those of the lateral ejaculatory ducts and are indicative of the different roles played by these structures in the organization of the spermatozoa bundles.
Assuntos
Código de Barras de DNA Taxonômico/métodos , Hemípteros/anatomia & histologia , Hemípteros/classificação , Animais , Ductos Ejaculatórios/anatomia & histologia , Ductos Ejaculatórios/ultraestrutura , Complexo IV da Cadeia de Transporte de Elétrons/genética , Hemípteros/genética , Masculino , Microscopia Eletrônica de Transmissão/métodos , Glândulas Seminais/anatomia & histologia , Glândulas Seminais/ultraestrutura , Espermatozoides/ultraestrutura , Sistema Urogenital/anatomia & histologia , Sistema Urogenital/ultraestruturaRESUMO
BACKGROUND: Assessment of rehabilitation outcome is based on measuring the change in Functional Independence Measure (FIMTM) score between the start and end of rehabilitation. However, the raw FIMTM score gain is subject to a ceiling effect. Proposed solutions to this problem have incongruities that limit their use. AIM: The aim of this study was to determine the factors that influence functional outcome in stroke rehabilitation, exploring the possibility of developing an outcome index free of the ceiling effect and of the incongruities revealed by the proposed solutions. DESIGN: Retrospective study of the electronic clinical records of patients admitted to a rehabilitation unit over a period of 5 years. SETTING: Rehabilitation unit. POPULATION: A total of 224 patients admitted for first post-stroke rehabilitation of either ischaemic or hemorrhagic etiology. METHODS: Rehabilitation outcome was evaluated based on changes in both raw and "normalized" FIMTM motor and cognitive scores observed between hospital admission and discharge. Normalized differences are in the range 0-1 and may be considered an estimate of the actually attained fraction of the maximum expected recovery, while the modified algebraic formula (+1 to both numerator and denominator) is intended to correct the incongruities observed in available solutions. Seventeen prognostic factors were selected as possible effect modifiers of the outcome. A multivariable model-building strategy, based on fractional polynomials, was adopted to select the significant factors, and the stability of the results. RESULTS: The procedure adopted to normalize both FIMTM outcomes resolves the ceiling effect and corrects the incongruities noted with available solutions. The level of disability at admission is confirmed as the strongest prognostic factor associated with both cognitive and motor outcomes. The onset-admission interval negatively influence motor recovery, bat not cognitive one. CONCLUSION: There is strong evidence to support the proposal that it is advantageous to measure functional recovery by means of the normalized change in FIMTM score. Following a rehabilitation programme, functional recovery should be evaluated separately for motor and cognitive domains. Rehabilitation program should begin as soon as possible. CLINICAL REHABILITATION IMPACT: Improved assessment of rehabilitation outcome leads to increased achievement of a favourable treatment outcome.
Assuntos
Avaliação da Deficiência , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral/fisiopatologia , Atividades Cotidianas , Idoso , Feminino , Humanos , Masculino , Recuperação de Função Fisiológica , Centros de Reabilitação , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The Research Institute for Fragrance Materials, Inc. (RIFM) has been engaged in the generation and evaluation of safety data for fragrance materials since its inception over 45 years ago. Over time, RIFM's approach to gathering data, estimating exposure and assessing safety has evolved as the tools for risk assessment evolved. This publication is designed to update the RIFM safety assessment process, which follows a series of decision trees, reflecting advances in approaches in risk assessment and new and classical toxicological methodologies employed by RIFM over the past ten years. These changes include incorporating 1) new scientific information including a framework for choosing structural analogs, 2) consideration of the Threshold of Toxicological Concern (TTC), 3) the Quantitative Risk Assessment (QRA) for dermal sensitization, 4) the respiratory route of exposure, 5) aggregate exposure assessment methodology, 6) the latest methodology and approaches to risk assessments, 7) the latest alternatives to animal testing methodology and 8) environmental risk assessment. The assessment begins with a thorough analysis of existing data followed by in silico analysis, identification of 'read across' analogs, generation of additional data through in vitro testing as well as consideration of the TTC approach. If necessary, risk management may be considered.
Assuntos
Academias e Institutos/legislação & jurisprudência , Qualidade de Produtos para o Consumidor/legislação & jurisprudência , Qualidade de Produtos para o Consumidor/normas , Exposição Ambiental/efeitos adversos , Perfumes/toxicidade , Animais , Dano ao DNA/efeitos dos fármacos , Árvores de Decisões , Relação Dose-Resposta a Droga , Determinação de Ponto Final/normas , Guias como Assunto , Humanos , Modelos Animais , Nível de Efeito Adverso não Observado , Perfumes/química , Perfumes/normas , Medição de Risco , Sociedades Científicas/legislação & jurisprudência , Sociedades Científicas/normasRESUMO
The aim of this work is to assess the level of the human alkaline phosphatase enzyme (ALP) during palatal expansion with Quad-Helix (QH) appliance. A total of twenty-two orthodontic patients characterized by contraction of the upper jaw, that needed application of a QH in order to treat their condition, were included in this study. Gingival crevicular fluid (GCF) was collected at four different times: before cementation (T0), after two weeks (T1), after four weeks (T2) and after one year (T3) from application of QH. In each patient maxillary first molars, right (UM-right) and left (UM-left), which were connected with bands to QH, were used for testing; first lower molars were used as Controls (LM-right, LM-left). Data show that ALP level in tension sites was proportional to the average increase of the inter-molar distance; on the contrary, the enzymatic level in compression sites was characterized by an inverse trend. The only exception to this phenomenon was recorded after one year (T3), when the increase of ALP level in both sites of tension and compression was ascribed to a mild inflammation due to bacterial plaque accumulation. The level of ALP in control sites was constant for the whole period of observation. The described ALP fluctuations in accordance with the inter-molar distance increment, shows that the main action of QH on bone remodelling was exerted during the fourth week (T2); for this reason, the monitoring of this enzyme could be used as a marker of effective function of the QH appliance.
Assuntos
Fosfatase Alcalina/análise , Líquido do Sulco Gengival/enzimologia , Aparelhos Ortodônticos , Adolescente , Adulto , Criança , Feminino , Humanos , MasculinoRESUMO
The spermatodesms of Tylopsis liliifolia form in the most proximal follicular cysts and are composed of a large number of sperm held together by a cap located in the anterior region of the acrosome. The cap is formed by short thin fibrils, loosely arranged at random, probably derived from secretory activity of cells of the cyst wall. Compared to other Tettigoniidae, a peculiar feature is acrosomal wings that twist gradually around the anterior region of the nucleus; at the end of the twisting process, the region of the sperm acrosome, observed in cross section, shows a typical spiral form. Spermatodesms do not undergo any substantial changes in the spermiduct. The epithelial cells of the wall have secretory activity and many show marked spermiophagic activity, which is conducted by epithelial cell protrusions that envelop the gametes, taking them into the cytoplasm. When removed from seminal vesicles and observed in vivo, spermatodesms show accentuated corkscrew movement, and when observed by SEM, slight torsion. Thus organized, spermatodesms are transferred to the spermatophore during mating, where they are transformed before reaching the seminal receptacle.
Assuntos
Ortópteros/fisiologia , Glândulas Seminais/metabolismo , Espermatogênese , Animais , Núcleo Celular/fisiologia , Citoplasma/metabolismo , Citoplasma/fisiologia , Células Epiteliais/metabolismo , Células Epiteliais/fisiologia , Masculino , Microscopia Eletrônica de Varredura , Ortópteros/anatomia & histologia , Ortópteros/metabolismo , Glândulas Seminais/fisiologia , Glândulas Seminais/ultraestrutura , Especificidade da Espécie , Motilidade dos Espermatozoides , Espermatozoides/citologia , Espermatozoides/fisiologiaRESUMO
A toxicologic and dermatologic review of phenethyl acetate when used as a fragrance ingredient is presented. Phenethyl acetate is a member of the fragrance structural group aryl alkyl alcohol simple acid esters (AAASAE). The AAASAE fragrance ingredients are prepared by reacting an aryl alkyl alcohol with a simple carboxylic acid (a chain of 1-4 carbons) to generate formate, acetate, propionate, butyrate, isobutyrate and carbonate esters. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for phenethyl acetate were evaluated, then summarized, and includes: physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, elicitation, toxicokinetics, repeated dose, genotoxicity, and carcinogenicity data. A safety assessment of the entire AAASAE will be published simultaneously with this document. Please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all AAASAE in fragrances.
Assuntos
Acetatos/toxicidade , Perfumes , Álcool Feniletílico/análogos & derivados , Acetatos/farmacocinética , Animais , Cobaias , Humanos , Camundongos , Álcool Feniletílico/farmacocinética , Álcool Feniletílico/toxicidade , Ratos , Pele/efeitos dos fármacos , Testes de ToxicidadeRESUMO
A toxicologic and dermatologic review of benzyl acetate when used as a fragrance ingredient is presented. Benzyl acetate is a member of the fragrance structural group aryl alkyl alcohol simple acid esters (AAASAE). The AAASAE fragrance ingredients are prepared by reacting an aryl alkyl alcohol with a simple carboxylic acid (a chain of 1-4 carbons) to generate formate, acetate, propionate, butyrate, isobutyrate and carbonate esters. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for benzyl acetate were evaluated, then summarized, and includes: physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, elicitation, phototoxicity, toxicokinetics, repeated dose, reproductive toxicity, genotoxicity, or carcinogenicity data. A safety assessment of the entire AAASAE will be published simultaneously with this document. Refer Belsito et al. (2012) for an overall assessment of the safe use of this material and all AAASAE in fragrances.
Assuntos
Compostos de Benzil/toxicidade , Perfumes , Animais , Compostos de Benzil/farmacocinética , Feminino , Humanos , Masculino , Camundongos , Coelhos , Ratos , Ratos Sprague-Dawley , Pele/efeitos dos fármacos , Suínos , Porco Miniatura , Testes de ToxicidadeRESUMO
A toxicologic and dermatologic review of phenethyl propionate when used as a fragrance ingredient is presented. Phenethyl propionate is a member of the fragrance structural group aryl alkyl alcohol simple acid esters (AAASAE). The AAASAE fragrance ingredients are prepared by reacting an aryl alkyl alcohol with a simple carboxylic acid (a chain of 1-4 carbons) to generate formate, acetate, propionate, butyrate, isobutyrate and carbonate esters. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for phenethyl propionate were evaluated, then summarized, and includes: physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, and elicitation data. A safety assessment of the entire AAASAE will be published simultaneously with this document. Please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all AAASAE in fragrances.
Assuntos
Perfumes , Propionatos/toxicidade , Animais , Humanos , Propionatos/farmacocinética , Coelhos , Ratos , Ratos Sprague-Dawley , Pele/efeitos dos fármacos , Testes de ToxicidadeRESUMO
A toxicologic and dermatologic review of benzyl alcohol when used as a fragrance ingredient is presented. Benzyl alcohol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a primary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C-(R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C-(R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for benzyl alcohol were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, elicitation, phototoxicity, photoallergy, toxicokinetics, repeated dose, reproductive toxicity, genotoxicity, and carcinogenicity data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances.
Assuntos
Álcool Benzílico/toxicidade , Perfumes , Animais , Álcool Benzílico/farmacocinética , Gatos , Cães , Humanos , Camundongos , Coelhos , Ratos , Pele/efeitos dos fármacosRESUMO
Ultrastructural investigations on the amphigonic reproductive mechanisms in Aphidoidea (Homoptera, Sternorryncha) species, of which little is known in the literature, can provide useful information on their reproductive biology. Morphological and ultrastructural investigations were carried out on the reproductive tract and on spermatozoa from sexually mature males of five species belonging to three subfamilies of Aphidoidea. The organization of the reproductive tract and of spermatozoa appears simple and similar in the examined species. Each testis consists of three follicles containing many cysts arranged in a progressive order of maturation from the distal to the proximal tract; spermiogenesis only occurs in sexually mature males, ending with the organization of sperm bundles. Gametes are neatly arranged in each bundle and kept together by a cap showing a particular organization. The distal tract of each spermiduct is enlarged and full of gametes; close to the testis the two spermiducts merge together, except in Drepanosiphum platanoidis where the spermiducts run independently. The various tracts of each examined gland showed no peculiar differences either in the same species or among the species. Some interesting hypotheses are proposed in this work about the probable roles of the investigated structures in the reproductive mechanisms of these insects.
Assuntos
Genitália Masculina/anatomia & histologia , Insetos/anatomia & histologia , Espermátides/ultraestrutura , Acrossomo/ultraestrutura , Animais , Axonema/ultraestrutura , Membrana Celular/ultraestrutura , Células Epiteliais/citologia , Insetos/classificação , Masculino , Microscopia Eletrônica , Microtúbulos/ultraestrutura , Especificidade da Espécie , EspermatogêneseRESUMO
Neurological deficits are a frequent complication of adult cardiac surgery. Dandy-Walker malformation (DWM) is a rare posterior fossa malformation defined by hypoplasia and upward rotation of the cerebellar vermis, cystic dilation of the fourth ventricle and, on occasion, hydrocephalus. We report an incidental diagnosis of DWM in an adult following coronary artery surgery complicated by delayed awakening.
Assuntos
Período de Recuperação da Anestesia , Anestesia/efeitos adversos , Procedimentos Cirúrgicos Cardíacos , Vasos Coronários/cirurgia , Síndrome de Dandy-Walker/complicações , Complicações Pós-Operatórias/etiologia , Idoso , Cuidados Críticos , Escala de Coma de Glasgow , Humanos , Masculino , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVES: Quantification of the complex, autonomic networks in the skin is difficult. Although sporadic attempts focusing mainly on sudomotor plexus have been reported, an easy and reliable method of quantification has not yet been made available. We developed a method to quantify pilomotor nerve fibers (PNFs), which, compared to sudomotor nerves, have a less complex pattern. We used this procedure on a population of normal and diabetic subjects, and propose it as a new tool to study cutaneous autonomic nerves. METHODS: Skin biopsies were performed from thigh and distal leg in 20 diabetic patients and 20 age- and sex-matched controls. Samples were processed applying indirect immunofluorescence and using pan-neuronal and selective markers for cholinergic and noradrenergic fibers. Pilomotor nerve fiber density was blindly calculated on single 2-µm optical sections selected from confocal z-stacks. Interobserver and intraobserver reliability was evaluated. Results were compared with values obtained by 2 other methods that explored PNFs more extensively. Pilomotor nerve fibers density was compared to epidermal nerve fiber (ENF) density, to pilocarpine-activated sweat gland density, and to the severity of neuropathy as assessed by the modified total neuropathy score. RESULTS: A significant loss of PNFs was found in diabetic subjects' thigh and leg. PNFs density did not correlate with ENF density, disease duration, or total neuropathy score. Noradrenergic PNFs correlated instead with sweating impairment. CONCLUSIONS: A reliable assessment of PNF density is possible. When studying cutaneous innervation, PNF quantification should be done to gain information on autonomic nerves in addition to somatic nerves.
Assuntos
Doenças do Sistema Nervoso Autônomo/patologia , Vias Autônomas/patologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Neuropatias Diabéticas/patologia , Pele/inervação , Adulto , Idoso , Contagem de Células , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 2/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pele/patologiaRESUMO
When considering expensive drug treatment for neonates and infants, how should we decide what we can and cannot afford? Accountably allocating health-care resources can be achieved using a framework that reflects the values a society considers so reflective of the collective will that they have been formally entrenched in law. The values and procedural mechanisms entrenched in the Canadian Charter of Rights and Freedoms are particularly helpful for those faced with these difficult spending decisions.
Assuntos
Custos de Medicamentos , Alocação de Recursos para a Atenção à Saúde/ética , Doenças do Recém-Nascido/tratamento farmacológico , Direitos do Paciente/ética , Seleção de Pacientes/ética , Valores Sociais , Canadá , Análise Custo-Benefício , Regulamentação Governamental , Alocação de Recursos para a Atenção à Saúde/legislação & jurisprudência , Política de Saúde , Humanos , Lactente , Recém-Nascido , Doenças do Recém-Nascido/economia , Direitos do Paciente/legislação & jurisprudência , Preconceito , Resultado do TratamentoRESUMO
The aim of the study was to test 1) whether chronic and stable coronary artery disease (CAD) could downregulate epicardial fat adrenomedullin synthesis and secretion, and decrease intracoronary plasma adrenomedullin levels, and 2) whether intracoronary plasma adrenomedullin levels could be related to epicardial adipose tissue adrenomedullin gene and protein expression in subjects with CAD. We examined 12 patients with CAD who required coronary artery bypass graft (CABG) and 10 patients with non-CAD who underwent cardiac surgery for valve replacement. Plasma levels of adrenomedullin were measured in peripheral vein circulation, in left coronary artery (LCA) and coronary sinus (CS) during coronary angiography. Epicardial adipose tissue biopsy for Reverse Transcription and Real-Time PCR (RT-PCR) adrenomedullin mRNA analysis and Western Blotting (WB) protein expression was performed during cardiac surgery in all subjects. Peripheral, LCA, and CS plasma adrenomedullin levels were significantly lower in CAD patients than in those with non-CAD (3.0+/-0.9 vs. 4.4+/-0.9 pg/ml p<0.01; 2.9+/-1 vs. 4.05+/-0.8 pg/ml, p<0.01, 3.1+/-0.9 vs. 3.98+/-0.9 pg/ml p=0.04, respectively). However, CS adrenomedullin levels were not statistically different than those in LCA suggesting that adrenomedullin was not secreted from epicardial fat into the coronary artery lumen. Epicardial fat adrenomedullin mRNA levels and protein expression were lower in patients with CAD than in those with non-CAD (p<0.01 for both). We conclude that 1) epicardial fat adrenomedullin gene and protein expression can be downregulated in CAD subjects, and 2) intracoronary adrenomedullin levels are lower in CAD. No evidence that epicardial adipose tissue really contributes intracoronary adrenomedullin can be provided at this time.
Assuntos
Tecido Adiposo/metabolismo , Adrenomedulina/análise , Adrenomedulina/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/metabolismo , Pericárdio/metabolismo , Tecido Adiposo/patologia , Adrenomedulina/genética , Idoso , Doença da Artéria Coronariana/fisiopatologia , Circulação Coronária , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Pericárdio/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) are well-recognized complications of obesity. This study was designed to evaluate the role of the UCP1 -3826 A>G polymorphism, adiponectin levels, leptin/adiponectin ratio (L/A), and main biochemical parameters in 102 unrelated severely obese adults [61 females and 41 males, median body mass index (BMI) = 47.8 kg/m2] with NAFLD, with (MS+) or without MS (MS-) from Southern Italy. SUBJECT AND METHODS: The UCP1 polymorphism was tested by the TaqMan method, main biochemical parameters by routinary methods, adiponectin, and leptin serum levels by enzyme-linked immunosorbent assay. MS was diagnosed according to the American Heart Association criteria, liver steatosis was detected by ultrasound. RESULTS: MS was present in 53% male and 66% female obese patients. Only total cholesterol (p=0.04 males and p=0.002 females) and L/A ratio (p=0.03 males) differed between MS+ and MS- obese patients. At multivariate analysis, severe liver steatosis was significantly associated with: UCP1 (AG+GG) genotypes [odds ratio-confidence interval (OR-CI): 4.25; 1.12-16.13], MS (OR-CI: 8.47; 1.78-40.25), low adiponectin levels (OR-CI: 0.92; 0.87-0.98), high alanine aminotransferase levels (OR-CI: 1.03; 1.00-1.06), age (ORCI: 1.08; 1.00-1.15), and male gender (OR-CI: 10.78; 1.61- 71.96). CONCLUSION: In addition to traditional factors, total cholesterol and L/A ratio appear to contribute to MS characterization in severe obesity. Furthermore, the UCP1 (AG+GG) genotypes and low adiponectin levels could predispose to a more severe liver steatosis independently of MS presence. Based on our data, polymorphic UCP1 (AG+GG) obese patients with low adiponectin levels appear to be high-risk subjects for worsening of liver steatosis, a NAFLD, possibly requiring a second-step evaluation by liver biopsy.
Assuntos
Adiponectina/metabolismo , Canais Iônicos/genética , Leptina/metabolismo , Proteínas Mitocondriais/genética , Obesidade Mórbida/genética , Obesidade Mórbida/metabolismo , Adiponectina/sangue , Adolescente , Adulto , Idoso , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Glicemia/análise , Colesterol/sangue , Fígado Gorduroso/sangue , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Feminino , Humanos , Insulina/sangue , Canais Iônicos/metabolismo , Itália , Leptina/sangue , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Proteínas Mitocondriais/metabolismo , Obesidade Mórbida/sangue , Polimorfismo de Nucleotídeo Único , Estatísticas não Paramétricas , Triglicerídeos/sangue , Proteína Desacopladora 1 , Adulto Jovem , gama-Glutamiltransferase/sangueRESUMO
BACKGROUND: The calcium sensitizer levosimendan has anti-ischaemic effects mediated via the opening of sarcolemmal and mitochondrial ATP-sensitive potassium channels. These properties suggest potential application in clinical situations where cardioprotection would be beneficial, such as cardiac surgery. We thus decided to investigate whether pharmacological pre-treatment with levosimendan reduces intensive care unit (ICU) length of stay in patients undergoing elective myocardial revascularization under cardiopulmonary bypass. METHODS: One hundred and six patients undergoing elective coronary artery bypass grafting were randomly assigned in a double-blind manner to receive levosimendan or placebo. Levosimendan (24 microg kg(-1)) or placebo was administered as a slow i.v. bolus over a 10 min period before the initiation of bypass. RESULTS: Tracheal intubation time and the length of ICU stay were significantly reduced in the levosimendan group (P<0.01). The number of patients needing inotropic support for >12 h was significantly higher in the control group (18.0% vs 3.8%; P=0.021). Compared with control patients, levosimendan-treated patients had lower postoperative troponin I concentrations (P<0.0001) and a higher cardiac power index (P<0.0001). CONCLUSIONS: Pre-treatment with levosimendan in patients undergoing surgical myocardial revascularization resulted in less myocardial injury, a reduction in tracheal intubation time, less requirement for inotropic support, and a shorter length of ICU stay.