RESUMO
Background: In the healthcare system, in the last 30 years, the prognostically negative value of the so-called Weekend Effect (WE) has been internationally recognized. The WE is regarded as the increased risk a patient might incur when hospitalized during non-working days, of enduring severe complications in comparison to the same hospitalization that occur on working days. The aim of this study was to retrospectively verify whether, once a mistake was made during weekends or on holidays, in comparison to a mistake occurred on workdays, it subsequently implied a higher risk of complications, death included, in a statistical and medico-legal way. Methods: Three different evaluators independently examined a total of 378 medico-legal cases over a more than 20-year period. Eventual medical actions and omissions were labelled as 'mistake' when the AJ claimed that at least one occurred; 'alleged mistake' included the cases where the EW's report disagreed with the AJ's one; finally, 'no mistake' when both the AJ and the EW agreed in their evaluations. During weekends there is a higher risk that a mistake occurs (OR=3.3, 95% CI=1.6;7.4; p-value<0.001) compared to weekdays. When death occurs, delayed diagnosis is the main cause (p=0.02), whereas a damaging action is more frequently claimed in general. Conclusions: We verified as actual the impact of the WE on patients' outcome from a medico-legal point of view. The implications for an improvement of the several settings of the Italian NHS are various, and many are the consequences in the healthcare management.
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Erros Médicos , Qualidade da Assistência à Saúde , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Plantão Médico/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Itália , Imperícia/estatística & dados numéricos , Imperícia/legislação & jurisprudência , Erros Médicos/estatística & dados numéricos , Erros Médicos/legislação & jurisprudência , Estudos Retrospectivos , Fatores de TempoRESUMO
Rainfall is generally accepted as one of the most important factors associated with an increased level of E. coli in bivalve molluscs. Performing microbiological risk assessment is relevant to official control authorities to determine the sanitary status of harvesting areas and, therefore, develop monitoring strategies and identify management practices that could be used to improve the quality and safety of the final product. The present study aimed to investigate the impact of rainfall on the content of E. coli in bivalve molluscs farmed in Sardinia (Italy). Enumeration of E. coli was performed according to the Most Probable Number (MPN) method (ISO 16649-3) on 1,920 bivalve samples collected from 7 regional counties between 2018 and 2020. Bivalve molluscs samples included 955 mussels (Mytilus galloprovincialis), 500 oysters (Crassostrea gigas), 325 clams (Ruditapes decussatus), 94 warty venus (Venus verrucosa), and 46 lagoon cockles (Cerastoderma glaucum). Rainfall data were obtained by the Department of Meteorology of the ARPA Sardegna. For each sampling site, GPS coordinates were used to identify gauge stations within catchment areas. Cumulative rain (mm) was recorded 1, 3, 5, 7, and 15 days before sampling, among which the 7-day cumulative rain was the strongest predictor of E. coli counts. Several thresholds of 7-day cumulative rain (from <10 mm up to >300 mm) before sampling were used to estimate the chances of a non-compliant sample (E. coli levels above the limit for sanitary class A; 230 MPN/100 g). The 7-day cumulative rain was positively associated with the chances of non-compliance. When the 7-day cumulative rain before sampling was >300 mm, 80.5 % of the samples were non-compliant, and the odds of a non-compliant sample were 23.6 times higher, as compared to samples harvested when the 7-day cumulative rainfall was <10 mm. Precipitation data could be a useful tool for interpreting anomalous results from official control authorities and reduce the costs that originate from closure of production areas.
Assuntos
Escherichia coli , Mytilus , Animais , Frutos do Mar/microbiologia , Moluscos , ItáliaRESUMO
OBJECTIVE: Herein we report clinical and virological data in a patient with COVID-19 infection and a prior history of kidney transplantation who had a good clinical recovery despite systemic infection. PATIENTS AND METHODS: Reverse transcriptase quantitative PCR analysis for the RdRp, N and E target genes detected viral RNA in different types of biological specimens. Whole viral genome sequences were obtained and analyzed from respiratory tract, feces and blood. RESULTS: Viral sequences showed high (~99.9%) homology with the Wuhan seafood market pneumonia virus. Phylogenetic analysis assigned of the SARS-CoV-2 strains to clade G. A rare variant in the orf1ab gene was present in both sequences, while a missense variant was detected only in viral RNA from stool. CONCLUSIONS: The evolution of the COVID-19 systemic infection in the patient presented here was favorable to the hypothesis that immunosuppressive therapy in organ transplant recipients might be involved in viral dissemination. A missense mutation was present in only one specimen from the same patient implying the occurrence of a mutational event in viral RNA, which is suggestive for the presence of an active virus, even though viral isolation is necessary to demonstrate infectivity.
Assuntos
COVID-19/virologia , Fezes/virologia , Transplante de Rim , Nasofaringe/virologia , RNA Viral/genética , Proteínas Virais/genética , Fezes/química , Feminino , Rejeição de Enxerto/prevenção & controle , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imunossupressores/uso terapêutico , Pessoa de Meia-Idade , Mutação de Sentido Incorreto/genética , Nasofaringe/química , Filogenia , Poliproteínas/genética , RNA Viral/sangue , SARS-CoV-2/genética , Análise de Sequência de RNARESUMO
The Evaluation of Therapeutic Community Treatments and Outcomes (VOECT) study was conducted in 131 Italian Therapeutic Communities (TCs) in 2008/2009. All of the patients entering residential treatment for drug or alcohol dependence were invited to participate. Data regarding patient socio-demographic characteristics, drug and alcohol consumption, health and psychopathological status, prior treatments and outcomes, and their motivation score were collected upon enrolment onto the study. The aim of this work was to identify the factors associated with allocation to short- versus long-term programmes in drug or alcohol dependent patients entering TCs in Italy. Of the 2470 patients included in the analysis, 30.8% were allocated to short-term treatment and 69.2% to long-term treatment. Several factors were significantly associated with the allocation to short- and long-term treatments: unstable living conditions; entering the TC when not detoxified; a high Symptom Checklist-90 somatization score; prior cessation episodes; previous in-patient detoxification treatments; psychosocial treatments; entering the TC by oneself; and a low motivation score.
Assuntos
Alcoolismo/reabilitação , Tratamento Domiciliar , Transtornos Relacionados ao Uso de Substâncias/reabilitação , Comunidade Terapêutica , Adulto , Alcoolismo/psicologia , Estudos de Coortes , Feminino , Humanos , Itália , Assistência de Longa Duração , Masculino , Pessoa de Meia-Idade , Psicoterapia Breve , Fatores de Tempo , Resultado do TratamentoRESUMO
The aim of the current work was to analyze, in the Sarda breed goat, genetic polymorphism within the casein genes and to assess their influence on milk traits. Genetic variants at the CSN1S1, CSN2, CSN1S2 and CSN3 gene loci were investigated using PCR-based methods, cloning and sequencing. Strong alleles prevailed at the CSN1S1 gene locus and defective alleles also were revealed. Null alleles were evidenced at each calcium-sensitive gene locus. At the CSN3 gene locus, we observed a prevalence of the CSN3 A and B alleles; the occurrence of rare alleles such as CSN3 B'', C, C', D, E and M; and the CSN3 S allele (GenBank KF644565) described here for the first time in Capra hircus. Statistical analysis showed that all genes, except CSN3, significantly influenced milk traits. The CSN1S1 BB and AB genotypes were associated with the highest percentages of protein (4.41 and 4.40 respectively) and fat (5.26 and 5.34 respectively) (P < 0.001). A relevant finding was that CSN2 and CSN1S2 genotypes affected milk protein content and yield. The polymorphism of the CSN2 gene affected milk protein percentage with the highest values recorded in the CSN2 AA goats (4.35, at P < 0.001). The CSN1S2 AC goats provided the highest fat (51.02 g/day) and protein (41.42 g/day) (P < 0.01) production. This information can be incorporated into selection schemes for the Sarda breed goat.
Assuntos
Caseínas/genética , Genótipo , Cabras/genética , Alelos , Animais , Cruzamento , Feminino , Frequência do Gene , Haplótipos , Masculino , Leite/química , Dados de Sequência Molecular , Família Multigênica , Polimorfismo GenéticoRESUMO
The diagnostic role of audio-impedancemetry in superior semicircular canal dehiscence (SSCD) disease is well known. In particular, since the first reports, the presence of evoked acoustic reflexes has represented a determining instrumental exhibit in differential diagnosis with other middle ear pathologies that are responsible for a mild-low frequencies air-bone gap (ABG). Even though high resolution computed tomography (HRCT) completed by parasagittal reformatted images still represents the diagnostic gold standard, several instrumental tests can support a suspect of labyrinthine capsule dehiscence when "suggestive" symptoms occur. Objective and subjective audiometry often represents the starting point of the diagnostic course aimed at investigating the cause responsible for the so-called "intra-labyrinthine conductive hearing loss". The purpose of this study is to evaluate the role of tympanometry, in particular of the inter-aural asymmetry ratio in peak compliance as a function of different mild-low frequencies ABG on the affected side, in the diagnostic work-up in patients with unilateral SSCD. The working hypothesis is that an increase in admittance of the "inner-middle ear" conduction system due to a "third mobile window" could be detected by tympanometry. A retrospective review of the clinical records of 45 patients with unilateral dehiscence selected from a pool of 140 subjects diagnosed with SSCD at our institution from 2003 to 2011 was performed. Values of ABG amplitude on the dehiscent side and tympanometric measurements of both ears were collected for each patient in the study group (n = 45). An asymmetry between tympanometric peak compliance of the involved side and that of the contralateral side was investigated by calculating the inter-aural difference and the asymmetry ratio of compliance at the eardrum. A statistically significant correlation (p = 0.015 by Fisher's test) between an asymmetry ratio ≥ 14% in favour of the pathologic ear and an ABG > 20 dB nHL on the same side was found. When "evocative" symptoms of SSCD associated with important ABG occur, the inter-aural difference in tympanometric peak compliance at the eardrum in favour of the "suspected" side could suggest an intra-labyrinthine origin for the asymmetry. Tympanometry would thus prove to be a useful instrument in clinical-instrumental diagnosis of SSCD in detection of cases associated with alterations of inner ear impedance.
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Testes de Impedância Acústica , Otopatias/diagnóstico , Canais Semicirculares , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Síndrome , Adulto JovemRESUMO
An imbalanced immune system has long been known to influence a variety of mood disorders including anxiety, obsessive-compulsive disorders and depression. In this study, we sought to model the impact of an immunocompromised state on these emotional behaviors using RAG-1â»/â» mice, which lack T and B cells. We also investigated the relative contribution of CD4⺠or CD8⺠T cells to these manifestations using RAG-1â»/â»/OT-II and RAG-1â»/â»/OT-I transgenic mice, respectively. Our results show that RAG-1â»/â» mice present a significant increase in digging and marble-burying activities compared with wild-type mice. Surprisingly, these anxiety-like behaviors were significantly reverted in RAG-1â»/â»/OT-II but not RAG-1â»/â»/OT-I transgenic mice. Immunodepletion experiments with anti-CD4 or anti-CD8 in C57/BL6 mice or repopulation studies in RAG-1â»/â» mice did not reproduce these findings. Microarray analysis of the brain of RAG-1â»/â» and RAG-1â»/â»/OT-II mice revealed a significantly different gene fingerprint, with the latter being more similar to wild-type mice than the former. Further analysis revealed nine main signaling pathways as being significantly modulated in RAG-1â»/â» compared with wild-type mice. Taken together, these results suggest that life-long rather than transient immunodeficient conditions influence the emotional behaviors in mice. Most interestingly, these effects seem to correlate with a specific absence of CD4⺠rather than CD8⺠T cells. Validation of these findings in man might provide new clues on the mechanism by which early life immune modulation might impact mood response in adults and provide a further link between immune and emotional well-being.
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Comportamento Animal/fisiologia , Linfócitos T CD4-Positivos/fisiologia , Linfócitos T CD8-Positivos/fisiologia , Emoções/fisiologia , Proteínas de Homeodomínio/fisiologia , Animais , Corticosterona/sangue , Citocinas/sangue , Citometria de Fluxo , Hospedeiro Imunocomprometido/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout/fisiologia , Reação em Cadeia da Polimerase em Tempo RealRESUMO
The putative 5-HT6 receptor agonist ST1936 has been shown to increase extracellular dopamine (DA) in the n.accumbens (NAc) shell and in the medial prefrontal cortex (PFCX). These observations suggest that 5-HT6 receptors modulate DA transmission in mesolimbic and mesocortical terminal DA areas. To investigate the behavioral counterpart of this interaction we studied in rats 1) the ability of ST1936 to maintain i.v. self-administration in fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement; 2) the effect of 5-HT6 receptor blockade on cocaine stimulated overflow of DA in dialysates from the PFCX and from the NAc shell and on cocaine i.v. self-administration. ST1936 was i.v. self-administered at unitary doses of 0.5-1 mg/kg on an FR1 and PR schedule of reinforcement, with breaking point of about 4. Pretreatment with the 5-HT6 antagonist SB271046 reduced by about 80% responding for ST1936. SB271046 also reduced cocaine-induced increase of dialysate DA in the NAc shell but not in the PFCX and impaired i.v. cocaine self-administration. These observations indicate that ST1936 behaves as a weak reinforcer and suggest that 5-HT6 receptors play a role in cocaine reinforcement via their facilitatory interaction with DA projections to the NAc shell. This novel 5-HT/DA interaction might provide the basis for a new pharmacotherapeutic strategy of cocaine addiction.
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Comportamento Aditivo/metabolismo , Cocaína/administração & dosagem , Dopamina/metabolismo , Receptores de Serotonina/metabolismo , Esquema de Reforço , Animais , Dopamina/fisiologia , Etilaminas/farmacologia , Indóis/farmacologia , Masculino , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Serotonina/fisiologia , AutoadministraçãoRESUMO
BACKGROUND: Portal vein arterialization (PVA) has shown efficacy to treat acute liver failure (ALF) in preclinical studies. The next step is to perform large animal studies that propose a clinically acceptable method of PVA. In this study, we assessed the efficacy of PVA using an extracorporeal device to treat 2 ALF models in swine. MATERIALS AND METHODS: The 2 ALF swine models were carbon tetrachloride toxic ALF and subtotal hepatectomy using 8 animals per group. PVA was performed with an extracorporeal device that may be suitable for future clinical studies. Arterial blood was drawn from the iliac artery and delivered into the portal vein for a 6-hour treatment. We analyzed biochemical, blood gas, and histological parameters as well as 1-week survival rates. RESULTS: In both models, ALF was successfully achieved. Control group animals deteriorated biochemically, dropping their prothrombin times and increasing the liver enzymes. In contrast, treated animals improved with a survival rate of 75% at 7 days compared with 0% for the former group. CONCLUSIONS: PVA using an extracorporeal device was feasible and effective to treat both toxic and resective ALF in swine.
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Oxigenação por Membrana Extracorpórea/métodos , Falência Hepática Aguda/terapia , Veia Porta , Animais , Modelos Animais de Doenças , Hepatectomia , Artéria Hepática , Circulação Hepática/fisiologia , Sistema Porta , Suínos , Resultado do TratamentoRESUMO
INTRODUCTION: Since the ischemia and reperfusion injury is one of the main causes of delayed graft function after transplantation, research efforts have focused on studying the molecules involved in this inflammatory process. The chemokine interleukin-8 (IL-8) seems to be the main one responsible through a chemoattractive action toward neutropils. Therefore, one of the strategies adopted to prevent this process is blocking the binding between IL-8 and its receptors. The aim of our study was to test the effect of meraxin, a new derivative from repertaxin, to protect the renal graft from ischemia and reperfusion injury. MATERIALS AND METHODS: Eighty male syngenic rats were divided into four groups. The control group underwent only kidney transplantation, while the other groups were treated with meraxin at various dosages 2 hours before graft reperfusion. Blood and histological samples were taken at sacrifice 24 hours after transplantation. RESULTS: Creatinine was significantly lower in the group treated with the high dosage of meraxin. Histological observation of the grafted tissue showed instead only a mild and not significant neutrophilic infiltration, equal in each group. CONCLUSIONS: Graft function was improved by the administration of meraxin at high dosage, but this effect did not seem to be connected to a reduction in inflammatory infiltration in the parechymal tissue. Maybe the cause is in the mechanisms of clotting activation, due to alteration of adhesion molecules and endothelial cells.
Assuntos
Interleucina-8/antagonistas & inibidores , Transplante de Rim/fisiologia , Circulação Renal/efeitos dos fármacos , Traumatismo por Reperfusão/prevenção & controle , Animais , Masculino , Ratos , Ratos Endogâmicos Lew , Transplante IsogênicoRESUMO
We reviewed the literature reports and our personal experience on partial portal vein arterialization (PPVA) to prevent and treat acute liver failure (ALF) following major hepatobiliary surgery or another etiology. Experimental studies in rats have assessed the efficacy of PPVA in treatment of ALF induced by extended resections in normal or fatty livers or in toxic carbon-tetrachloride damage. The treated groups showed greater survival and faster recovery of liver function. Among 11 clinical cases reported in the literature, PPVA was performed in four cases to prevent and in seven cases to treat ALF. Eight patients survived, showing rapid recovery of liver function and resolution of the clinical condition. This relatively simple procedure has shown itself able to promote liver regeneration. The PPVA procedure has shown itself to be safe and simple as well as to offer a promising approach to the failing liver.
Assuntos
Artéria Hepática , Circulação Hepática , Regeneração Hepática/fisiologia , Transplante de Fígado/métodos , Veia Porta/cirurgia , Humanos , Falência Hepática/prevenção & controle , Falência Hepática/terapia , Complicações Pós-Operatórias/prevenção & controleRESUMO
BACKGROUND: Resident psychiatrists in the Netherlands, unlike their counterparts in other countries, are obliged to undergo 50 hours of personal psychotherapy. In 1994 Trijsburg et al. published the results of a questionnaire that had been completed by psychiatrists, psychologists and other persons training to become psychotherapists. AIM: To fnd out how resident psychiatrists in Amsterdam in 2003 characterised and rated the therapy module in their course. METHOD: Resident psychiatrists in Amsterdam were asked to complete a shortened version of the 1994 questionnaire. The Utrecht Burn-out Scale was added. RESULTS: Personal therapy was greatly appreciated, but the psychotherapists were more convinced of the positive effects than were the residents. Hardly anyone referred to any negative aspects. The residents did not consider personal therapy to be an essential element in their course. Two-thirds of the residents in Amsterdam were female, a large increase compared to the male-female ratio in 1994. The workload of the residents was in accordance with that of other workers in the health care sector. CONCLUSION: Since resident psychiatrists in Amsterdam have a positive attitude to compulsory personal therapy, there seems to be no compelling reasonfor abolishing this module--even though the beneficial effects of this therapy have never been demonstrated.
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Internato e Residência , Psiquiatria/educação , Terapia Psicanalítica/métodos , Estudantes de Medicina/psicologia , Adulto , Avaliação Educacional/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Inquéritos e QuestionáriosRESUMO
The selectively bred Roman high- and low-avoidance rats differ in emotionality and responsiveness to the motor effects of acute and repeated psychostimulant administration. These lines also show drastic differences in the neurochemical responses of their mesolimbic dopamine systems to addictive drugs. The nucleus accumbens is critically involved in the locomotor activation produced by psychostimulants and in the augmentation of this effect observed upon repeated drug administration (i.e. behavioral sensitization), although there is not a general consensus as to whether the nucleus accumbens-core or the nucleus accumbens-shell is preferentially involved in such alterations. This study was designed to evaluate the effects of acute amphetamine (0.20 mg/kg, s.c.) on dopamine output in the nucleus accumbens-shell and nucleus accumbens-core of the Roman lines under basal conditions (i.e. naïve rats) and after the repeated administration of amphetamine (1 mg/kg, s.c. x 10 days) or saline. We show that (1) in naïve rats, amphetamine caused a larger increment in dopamine output in the nucleus accumbens-shell vs the nucleus accumbens-core only in the Roman high-avoidance line; (2) repeated amphetamine elicits behavioral sensitization in Roman high-avoidance, but not Roman low-avoidance, rats; (3) in sensitized Roman high-avoidance rats, amphetamine provokes a larger increment in dopamine output in the nucleus accumbens-core, and an attenuated dopaminergic response in the nucleus accumbens-shell, as compared with Roman high-avoidance rats repeatedly treated with saline; and (4) such neurochemical changes are not observed in the mesoaccumbens dopaminergic system of the sensitization-resistant Roman low-avoidance line. We propose that (1) Roman high-avoidance and Roman low-avoidance rats differ in the vulnerability to develop psychostimulant sensitization, (2) the nucleus accumbens-core and nucleus accumbens-shell subserve distinct functional roles in this phenomenon, and (3) comparative studies in the Roman lines may provide insight into the influence of neural substrates and genetic background on the individual vulnerability to addiction.
Assuntos
Anfetamina/farmacologia , Aprendizagem da Esquiva/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/farmacologia , Dopamina/metabolismo , Núcleo Accumbens/metabolismo , Anfetamina/administração & dosagem , Animais , Comportamento Animal/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/administração & dosagem , Masculino , Microdiálise , Núcleo Accumbens/anatomia & histologia , Ratos , Ratos EndogâmicosRESUMO
There is strong evidence that altered immunological function entails an increased risk of lymphoma, although the current knowledge of aetiological factors for lymphomas is limited. The CTLA4 gene encodes a receptor that provides a negative signal to the T-cell once an immune response is initiated and completed. We analysed the 2q33 chromosomal region harbouring CD28, CTLA4 and ICOS genes, which are closely linked and have related functions in immune regulation, for association in 100 non-Hodgkin's lymphoma (NHL) patients and in 128 healthy controls; both groups originated from Sardinia. There was a strong association of the CTLA4 49A and the 3'-untranslated region (AT)(82) alleles with NHL [odds ratio (OR) = 2, 95% confidence interval (CI) = 1.2-3.2, and OR = 1.6, 95% CI = 1.1-2.4 respectively]. CTLA4-318C:49A:(AT)(82) was the most represented haplotype in the studied population and was associated with NHL (P = 0.0029, OR = 1.76, 95% CI = 1.2-2.5). Strong linkage disequilibrium was detected between CD28, CTLA4 and ICOS and a 'common' haplotype was found very frequently among NHLs. However, no independent association between CD28, ICOS, D2S72 markers and NHL was observed. Our findings enable CTLA4 from adjacent functionally related genes as the true causative risk gene for NHL susceptibility at least in Sardinian patients.
Assuntos
Antígenos de Diferenciação de Linfócitos T/genética , Antígenos de Diferenciação/genética , Antígenos CD28/genética , Cromossomos Humanos Par 2/genética , Linfoma não Hodgkin/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD , Antígeno CTLA-4 , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Proteína Coestimuladora de Linfócitos T Induzíveis , Desequilíbrio de Ligação , Linfoma não Hodgkin/imunologia , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoAssuntos
Diabetes Mellitus Tipo 1/genética , Nefropatias Diabéticas/genética , Resistência à Insulina/genética , Proteínas Tirosina Fosfatases/genética , Regiões 3' não Traduzidas , Adulto , Diabetes Mellitus Tipo 1/complicações , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína Tirosina Fosfatase não Receptora Tipo 1RESUMO
The selective breeding of Roman high- (RHA/Verh) and low-avoidance (RLA/Verh) rats for rapid versus poor acquisition of active avoidant behaviour has produced two behavioural phenotypes with different performances in a variety of animal models of anxiety, in which RLA/Verh rats are consistently more fearful than RHA/Verh rats. In addition, these two lines display different functional properties of brain neurotransmitters like serotonin (5-HT), known to be involved in the expression of anxiety- and depression-related behaviours. Therefore, we used brain microdialysis and [3H]-citalopram binding autoradiography to characterize further the neurochemical properties of 5-HTergic transmission in the two lines. No significant line-related differences were detected in the basal 5-HT output in the frontoparietal cortex (FPCx). In contrast, the increase in the cortical 5-HT output elicited by the systemic administration or the local application, via reverse dialysis, of chlorimipramine and fluoxetine was more robust in RHA/Verh than in RLA/Verh rats. Moreover, the binding signal of [3H]-citalopram to 5-HT re-uptake sites was more intense in the FPCx of RHA/Verh rats than in their RLA/Verh counterparts. These findings suggest that the functional tone of the 5-HTergic projection to the FPCx is stronger in the RHA/Verh line relative to the RLA/Verh line. It is proposed that RLA/Verh rats may be used as a model with heuristic value for studying the role of 5-HTergic transmission in anxiety and in the anxiolytic effects of monoamine re-uptake inhibitors.
Assuntos
Aprendizagem da Esquiva/fisiologia , Sistema Nervoso Central/fisiologia , Serotonina/metabolismo , Transmissão Sináptica/fisiologia , Animais , Ansiedade/genética , Autorradiografia , Comportamento Animal/fisiologia , Ligação Competitiva/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/fisiologia , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/metabolismo , Citalopram/farmacocinética , Clomipramina/farmacologia , Depressão/genética , Fluoxetina/farmacologia , Masculino , Microdiálise , Ratos , Ratos Endogâmicos , Inibidores Seletivos de Recaptação de Serotonina/farmacocinética , Especificidade da Espécie , Transmissão Sináptica/genética , TrítioRESUMO
The mesocortical and mesolimbic dopaminergic (DAergic) pathways are activated by either aversive or rewarding stimuli. The functional tone of these DAergic neurons also increases during the execution of cognitive tasks. The present study was designed to examine the relationship between mesocortical and mesolimbic DAergic function and the expression of fear-related behaviours as compared with attention- and cognition-related mechanisms (e.g. coping strategies), in response to aversive conditions. To this aim, we used two psychogenetically selected rat lines, Roman high-avoidance (RHA/Verh) and Roman low-avoidance (RLA/Verh), which display drastically different emotion- and coping-related behaviours in response to stressors: RLA/Verh rats are 'reactive copers' and more fearful than RHA/Verh rats, which are 'proactive copers'. Brain dialysis experiments demonstrated that tail-pinch (TP) and the anxiogenic compounds pentylenetetrazol (PTZ) and ZK 93426 increased DA output in the medial prefrontal cortex (PFCX) of RHA/Verh but not RLA/Verh, rats. In contrast, in the shell compartment of the nucleus accumbens (NAC shell), TP caused a small increase in DA output only in RLA/Verh rats, whereas PTZ and ZK 93426 had no significant effect on either line. RHA/Verh rats displayed more robust and longer lasting coping activity and less frequent freezing and self-grooming episodes than did RLA/Verh rats after TP, PTZ or ZK 93426. This dissociation between fear-related behaviour and cortical DAergic activation argues against the view that the latter may be involved in the control of fear-like responses. We therefore propose that the activation of mesocortical DAergic projections by aversive stimuli underlies the cognitive mechanisms that are triggered in an attempt to gain control over the stressor.
Assuntos
Aprendizagem da Esquiva , Condicionamento Psicológico , Dopamina/metabolismo , Medo/fisiologia , Estresse Fisiológico , Animais , Comportamento Animal , Química Encefálica , Dopamina/análise , Comportamento Exploratório , Antagonistas GABAérgicos/efeitos adversos , Masculino , Microdiálise/métodos , Atividade Motora/fisiologia , Núcleo Accumbens/metabolismo , Córtex Pré-Frontal/metabolismo , Ratos , Ratos Endogâmicos , Tempo de Reação , Especificidade da Espécie , Estresse Fisiológico/induzido quimicamente , Fatores de TempoRESUMO
UNLABELLED: Background genetic factors may influence the variability in the rate of progression of kidney disease in type 1 diabetes. In diabetes, progressive mesangial matrix expansion and glomerular sclerosis are, to a large extent, mediated by TGF-beta1. Decorin, a proteoglycan which is a component of the extracellular matrix, regulates TGF-beta1 activity and expression. We have examined the relationship between the 179/183/185 polymorphism of the Decorin gene and the progression of diabetic nephropathy. METHODS: From a cohort of 175 European patients with diabetic nephropathy, we studied 79 patients who were selected because they had a follow-up of at least 2 years (average 6.5 years; range: 2.5-15 years), and regular measurements of serum creatinine on 5 or more occasions. Creatinine clearance (CrCl) calculated from serum creatinine concentration was used as a measure of derived glomerular filtration rate (dGFR). All patients were on antihypertensive therapy. RESULTS: The rate of dGFR decline in the whole cohort was [median (range)] 4.6 (-3.8 to 18) ml/min/year. No patient with 185 allele was found. Patients with 179/183 and 179/179 genotype (n = 14), who were considered together and named 179 carriers, had a slower rate of GFR decline [2.1 (0.06-11.7) ml/min/year] as compared to patients with Decorin 183/183 genotype (n = 65) [5.6 (-3.8 to 18) ml/min/year; p < 0.001]. In addition, when considering individual data, patients carrying the 179 allele had a 3.0 (95%CI: 1.8-4.2)-fold higher probability to be slow progressors (i.e. GFR decline below the median). This difference could not be accounted for by differences in duration of disease, type and duration of antihypertensive therapy, albumin excretion rate, blood glucose or blood pressure control. In a multivariate logistic analysis albumin excretion rate (p < 0.001), mean arterial pressure (p = 0.07) and Decorin gene polymorphism (p = 0.036), but not HbA1c, were independently correlated with the rate of dGFR fall. CONCLUSION: The 179 allele variant of the Decorin gene is related to a slower progression of DN in type 1 diabetic patients with albuminuria and receiving antihypertensive therapy.
Assuntos
Diabetes Mellitus Tipo 1/genética , Nefropatias Diabéticas/genética , Polimorfismo Genético , Proteoglicanas/genética , Adulto , Alelos , Células Cultivadas , Creatinina/sangue , Decorina , Progressão da Doença , Proteínas da Matriz Extracelular , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Genótipo , Humanos , Masculino , Proteinúria/genética , Pele/citologiaRESUMO
The aim of this study was to evaluate the levels of stress, anxiety and depression in women caregivers of Alzheimer's disease patients. A convenience sample of 37 women caregivers living with the patients was studied using a descriptive-correlational design. A sociodemographic questionnaire with scales measuring the variables taken into consideration were utilized. Caregivers were 60 years old, devoted to the patients 17 hours of caring per day and had only 1 hour for their personal needs. The 54, 21 and 29% of the sample had high levels respectively at the stress, anxiety and depression scale. Stress, anxiety and depression were positively correlated with caring hours, sleep problems in caregivers and behavioural disturbances of the patients; and were negatively correlated with free time and time spent out of the home. Implications for nursing care resulting from this study consists in giving more support to caregivers in order to avoid their excessive involvement in caring and in guaranteeing educational interventions to help caregivers to manage the behavioural disturbances of the patients.
Assuntos
Doença de Alzheimer , Ansiedade/epidemiologia , Cuidadores/psicologia , Depressão/epidemiologia , Assistência Domiciliar/psicologia , Estresse Fisiológico/epidemiologia , Adulto , Idoso , Doença de Alzheimer/enfermagem , Ansiedade/etiologia , Depressão/etiologia , Família , Feminino , Humanos , Itália , Pessoa de Meia-Idade , Modelos Psicológicos , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Distúrbios do Início e da Manutenção do Sono/etiologia , Fatores Socioeconômicos , Estresse Fisiológico/etiologia , Inquéritos e QuestionáriosRESUMO
Although most imprinted genes show allelic differences in DNA methylation, it is not clear whether methylation regulates the expression of some or all imprinted genes in somatic cells. To examine the mechanisms of silencing of imprinted alleles, we generated novel uniparental mouse embryonic fibroblasts exclusively containing either the paternal or the maternal genome. These fibroblasts retain parent-of-origin allele-specific expression of 12 imprinted genes examined for more than 30 cell generations. We show that p57(Kip2) (cyclin-dependent kinase inhibitor protein 2) and Igf2 (insulin-like growth factor 2) are induced by inhibiting histone deacetylases; however, their activated state is reversed quickly by withdrawal of trichostatin A. In contrast, DNA demethylation results in the heritable expression of a subset of imprinted genes including H19 (H19 fetal liver mRNA), p57(Kip2), Peg3/Pw1 (paternally expressed gene 3), and Zac1 (zinc finger-binding protein regulating apoptosis and cell cycle arrest). Other imprinted genes such as Grb10 (growth factor receptor-bound protein 10), Peg1/Mest (paternally expressed gene 1/mesoderm-specific transcript), Sgce (epsilon-sarcoglycan), Snrpn (small nuclear ribonucleoprotein polypeptide N), and U2af1 (U2 small nuclear ribonucleoprotein auxiliary factor), remain inactive, despite their exposure to inhibitors of histone deacetylases and DNA methylation. These results demonstrate that changes in DNA methylation but not histone acetylation create a heritable epigenetic state at some imprinted loci in somatic cells.