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1.
J Robot Surg ; 16(6): 1471-1481, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35254601

RESUMO

Robot-assisted donor nephrectomy (RDN) is increasingly used due to its advantages such as its precision and reduced learning curve when compared to laparoscopic techniques. Concerns remain among surgeons regarding possible longer warm ischemia time. This study aimed to compare patients undergoing robotic living donor nephrectomy to the more frequently used hand-assisted laparoscopic nephrectomy (HLDN) technique, focusing on warm ischemia time, total operative time, learning curve, hospital length of stay, donor renal function and post-operative complications. Retrospective study comparing RDN to HLDN in a collaborative transplant network. 176 patients were included, 72 in RDN and 104 in HLDN. Left-sided nephrectomy was favored in RDN (82% vs 52%, p < 0.01). Operative time was longer in RDN (287 vs 160 min; p < 0.01), while warm ischemia time was similar (221 vs 213 secs, p = 0.446). The hospital stay was shorter in RDN (3.9 vs 5.7 days, p < 0.01).Concerning renal function, a slightpersistent increase of 7% of the creatinine ratio was observed in the RDN compared to the HLDN group (1.56 vs 1.44 at 1-month checkup, p < 0.01). The results show that RDN appears safe and efficient in comparison to the gold-standard HLDN technique. Warm ischemia time was similar for both techniques, whereas RDN operative time was longer. Patients undergoing RDN had a shorter hospital stay, this being possibly mitigated by differences in center release criteria. Donor renal function needs to be assessed on a longer-term basis for both techniques.


Assuntos
Laparoscopia Assistida com a Mão , Transplante de Rim , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Transplante de Rim/métodos , Doadores Vivos , Procedimentos Cirúrgicos Robóticos/métodos , Estudos Retrospectivos , Creatinina , Nefrectomia/métodos , Laparoscopia/métodos , Rim/cirurgia , Rim/fisiologia
2.
Psychol Psychother ; 94 Suppl 2: 223-241, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32154644

RESUMO

OBJECTIVE: Increasing evidence suggests experiences of childhood trauma may be causally related to the development of hallucinations. Cognitive theories of psychosis suggest post-traumatic intrusions to be a primary mechanism in this relationship. These theories predict that the content of hallucinations will be related to traumatic experiences; however, few studies have investigated this. This study examined the relationship between childhood trauma, the content of hallucinations, and the content of post-traumatic intrusions in a sample with first-episode psychosis. METHODS: Sixty-six young people aged 15-25 experiencing a first episode of psychosis were recruited from an early intervention service. Participants completed assessments of traumatic experiences, hallucination content, and post-traumatic intrusion content using a systematic coding frame. The coding frame assessed for three types of relationships between traumatic experiences, the content of hallucinations, and the content of post-traumatic intrusions: direct relationships (hallucination content exactly matching the trauma/intrusion), thematic relationships (hallucinations with the same themes as the trauma/intrusion), and no relationship (hallucination and trauma/intrusion content unrelated). RESULTS: Of those people who reported trauma and hallucinations (n = 36), 22 of these (61%) experienced post-traumatic intrusions, and of these, 16 (73%) experienced hallucinations that were directly or thematically related to their post-traumatic intrusions. Twelve people experienced hallucination content directly related to their trauma, six of whom (50%) also had intrusions relating to the same traumatic event as their hallucinations. CONCLUSIONS: The finding that some people experience hallucinations and post-traumatic intrusions relating to the same traumatic event supports theories proposing a continuum of memory intrusion fragmentation. These results indicate that early intervention services for young people with psychosis should provide assessment and intervention for trauma and PTSD and should consider the impact of past traumatic events on the content of current hallucinatory experience. PRACTITIONER POINTS: Trauma and post-traumatic stress disorder should be assessed in those experiencing a first episode of psychosis. Interventions for trauma should be offered in early intervention for psychosis services. In a notable proportion of people, hallucination content is related to traumatic experiences. Clinical assessment and formulation of hallucinations requires consideration of how past traumatic events may be contributing to hallucinatory experience. It is important for clinicians to have an understanding of the phenomenological differences between hallucinations and post-traumatic intrusions when conducting clinical assessments with people with comorbid psychosis and PTSD.


Assuntos
Transtornos Psicóticos , Transtornos de Estresse Pós-Traumáticos , Adolescente , Alucinações , Humanos
3.
Transpl Int ; 32(5): 459-469, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30903673

RESUMO

The lack of suitable kidney donor organs has led to rising numbers of patients with end stage renal disease waiting for kidney transplantation. Despite decades of clinical experience and research, no evaluation process that can reliably predict the outcome of an organ has yet been established. This review is an overview of current methods and emerging techniques in the field of donor kidney evaluation prior to transplantation. Established techniques like histological evaluation, clinical scores, and machine perfusion systems offer relatively reliable predictions of delayed graft function but are unable to consistently predict graft survival. Emerging techniques including molecular biomarkers, new imaging technologies, and normothermic machine perfusion offer innovative approaches toward a more global evaluation of an organ with better outcome prediction and possibly even identification of targets for therapeutic interventions prior to transplantation. These techniques should be studied in randomized controlled trials to determine whether they can be safely used in routine clinical practice to ultimately reduce the discard rate and improve graft outcomes.


Assuntos
Falência Renal Crônica/cirurgia , Transplante de Rim , Obtenção de Tecidos e Órgãos/métodos , Animais , Biomarcadores/metabolismo , Biópsia , Função Retardada do Enxerto , Sobrevivência de Enxerto , Humanos , Rim , Metabolômica , Preservação de Órgãos/métodos , Perfusão , Proteômica , Suínos , Doadores de Tecidos , Resultado do Tratamento
4.
Br J Clin Psychol ; 58(2): 154-172, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30421797

RESUMO

OBJECTIVE: There is increasing evidence that childhood trauma may play a role in the aetiology of psychosis. Cognitive models implicate trauma-related symptoms, specifically post-traumatic intrusions and trauma-related beliefs as primary mechanisms, but these models have not been extensively tested. This study investigated relationships between childhood trauma, psychotic symptoms (hallucinations and delusions), post-traumatic intrusions, and trauma-related beliefs while accounting for comorbid symptoms. METHODS: Sixty-six people with first episode psychosis aged between 15 and 24 years were assessed for hallucinations, delusions, childhood trauma, post-traumatic intrusions, post-traumatic avoidance, and trauma-related beliefs. RESULTS: Fifty-three per cent of the sample had experienced childhood trauma, and 27% met diagnostic criteria for post-traumatic stress disorder. Both post-traumatic intrusions and trauma-related beliefs mediated the relationships between childhood trauma and hallucinations, and childhood trauma and delusions. Multiple regression analyses revealed that post-traumatic intrusions (but not childhood trauma, post-traumatic avoidance, or trauma-related beliefs) were independently associated with hallucination severity (ß = .53, p = .01). Post-traumatic intrusions and trauma-related beliefs (but not childhood trauma or post-traumatic avoidance) were independently associated with delusion severity (ß = .67, p < .01 and ß = .34, p < .01, respectively). CONCLUSIONS: These findings support cognitive models that implicate post-traumatic intrusions in hallucination aetiology, and post-traumatic intrusions and trauma-related beliefs in delusion aetiology. The results suggest that trauma and post-traumatic stress disorder, including trauma-related beliefs, should be addressed in the assessment and treatment of people with early psychosis. PRACTITIONER POINTS: Trauma and post-traumatic stress disorder, including trauma-related beliefs, should be addressed in the assessment and treatment of people with early psychosis. Routine assessment of childhood trauma and PTSD in clinical services dealing with young people with first episode psychosis is needed. These findings support cognitive models of trauma and hallucinations and delusions.


Assuntos
Delusões/psicologia , Alucinações/psicologia , Transtornos Psicóticos/psicologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Adolescente , Adulto , Comorbidade , Feminino , Humanos , Masculino , Adulto Jovem
5.
Early Interv Psychiatry ; 13(6): 1366-1372, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30585427

RESUMO

AIM: Increasing evidence suggests that childhood trauma and dissociation are associated with psychotic symptoms and disorders. Significant rates of dissociative disorders and clinical levels of dissociative symptoms are found in chronic schizophrenia. To date, no studies have examined the prevalence of these in a first episode psychosis (FEP) group. This study aimed to investigate the prevalence of dissociative disorders and symptoms in a FEP sample as well as the prevalence of severe dissociative symptoms in those with or without experiences of childhood trauma. METHODS: Sixty-six young people with FEP completed a research interview which included the structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) Axis I Disorders, Childhood Trauma Questionnaire and the Structured Clinical Interview for DSM-IV Dissociative Disorders-Revised. RESULTS: Dissociative symptoms at clinical levels were found in 36.4% of the sample. Furthermore, 13.6% of the sample met diagnostic criteria for a lifetime dissociative disorder. Significant differences in the frequency of clinical dissociative symptoms between those with or without childhood trauma were also found. CONCLUSIONS: Dissociative symptoms should be routinely assessed for in early intervention settings, especially in cases where childhood trauma is disclosed or suspected. Where present, dissociative symptoms should also be incorporated into subsequent case formulation and treatment planning.


Assuntos
Adultos Sobreviventes de Eventos Adversos na Infância/psicologia , Transtornos Dissociativos/epidemiologia , Transtornos Psicóticos/epidemiologia , Adolescente , Adulto , Austrália/epidemiologia , Estudos de Casos e Controles , Comorbidade , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Prevalência , Inquéritos e Questionários , Adulto Jovem
6.
Transpl Int ; 31(8): 917-929, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29603452

RESUMO

The microbiological safety of islet preparations is paramount. Preservation medium contamination is frequent, and its impact on islet yield and function remains unclear. Microbiological samples collected during islet isolations from 2006 to 2016 were analyzed and correlated to isolation and allo- and autotransplantation outcomes. Microbial contamination of preservation medium was found in 64.4% of processed donor pancreases (291/452). We identified 464 microorganisms including Staphylococcus (253/464, 54.5%), Streptococcus (31/464, 6.7%), and Candida species (25/464, 5.4%). Microbial contamination was associated with longer warm and cold ischemia times and lower numbers of postpurification islet equivalents, purity, transplant rate, and stimulation index (all P < 0.05). Six percent of the preparations accepted for transplantation showed microbial contamination after isolation (12/200); 9 of 12 were Candida species. Six patients were transplanted with a sample with late microbial growth discovered after the infusion. Insulin independence rate was not affected. This risk of transplanting a contaminated islets preparation was reduced by half following the implementation of an additional sampling after 24 h of islet culture. Pancreas preservation fluid microbial contamination is associated with lower transplant rate and poorer in vitro function, but not with changes in graft survival. Culture medium testing 1 day after isolation reduces the risk of incidental transplantation with contaminated islets.


Assuntos
Contaminação de Medicamentos/estatística & dados numéricos , Transplante das Ilhotas Pancreáticas/estatística & dados numéricos , Soluções para Preservação de Órgãos , Adolescente , Adulto , Idoso , Criança , Estudos de Coortes , Feminino , Humanos , Ilhotas Pancreáticas/microbiologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
7.
Compr Psychiatry ; 84: 68-74, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29694935

RESUMO

BACKGROUND: Childhood trauma has been linked to the presence of delusions and hallucinations in psychosis, although the mechanisms underlying this relationship require elucidation. Dissociation, characterized by disruptions to the integrative functioning of several core mental domains, has emerged as a potential mechanism. There is a paucity of research using a clinician-rated measure of dissociation to test the indirect effect of dissociation on the relationship between childhood trauma and psychotic symptoms. This study aimed to investigate whether dissociation mediated both the relationships between childhood trauma and hallucinations, and childhood trauma and delusions utilizing a clinician-administered measure of dissociation, namely the Structured Clinical Interview for DSM-IV Dissociative Disorders - Revised (SCID-D-R). METHOD: Sixty-six first-episode psychosis (FEP) participants completed a research interview and questionnaires. Information about experiences of childhood trauma, psychosis, dissociation, general psychopathology and demographics were collected. RESULTS: When using the SCID-D-R, childhood trauma positively correlated with dissociation. Further, dissociation mediated the relationship between childhood trauma and delusions. Contrary to previous findings, we found no relationship between dissociation and hallucinations and no mediating effect of dissociation on the association between childhood trauma and hallucinations. The results of the SCID-D-R differed significantly from those of the Dissociative Experiences Scale-II (DES-II) which were consistent with previous research. CONCLUSIONS: Our findings are the first to use a clinician-rated measure to test the mediating effect of dissociation on the relationship between childhood trauma and positive symptoms (i.e., hallucinations and delusions). Given the discrepancies in results between the SCID-D-R and DES-II, how dissociation is measured in future research is an important consideration. The results add to a body of work that increasingly recognizes the importance of dissociative symptoms on the relationship between childhood trauma and psychosis. The results suggest that dissociative symptoms should be part of routine assessment in those with a history of trauma and present to FEP services.


Assuntos
Experiências Adversas da Infância/tendências , Delusões/psicologia , Transtornos Dissociativos/psicologia , Alucinações/psicologia , Transtornos Psicóticos/psicologia , Adolescente , Adulto , Criança , Estudos Transversais , Delusões/diagnóstico , Delusões/epidemiologia , Transtornos Dissociativos/diagnóstico , Transtornos Dissociativos/epidemiologia , Feminino , Alucinações/diagnóstico , Alucinações/epidemiologia , Humanos , Masculino , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/epidemiologia , Estudos Retrospectivos , Inquéritos e Questionários , Vitória/epidemiologia , Adulto Jovem
8.
Work ; 56(4): 581-589, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28339416

RESUMO

BACKGROUND: Cognitive Adaptation Training (CAT) uses compensatory strategies and environmental supports to support cognitive impairments and improve functioning. CAT may be useful for addressing vocational recovery in first-episode psychosis (FEP) because cognitive impairments are common and vocational recovery is a key goal of young people with FEP. OBJECTIVE: To describe clinical observations and practice experience when delivering CAT with FEP clients and explore potential benefits via objective outcome measures for improving vocational outcomes. METHODS: In this pilot study, five FEP participants received 9 months of CAT. Participant goals and functional needs and clinical observations were recorded. Formal measures of functioning, quality of life and motivation were independently administered pre- and post-intervention. RESULTS: Vocational recovery (education, employment) was found to be a primary functional goal of FEP participants. Accordingly, CAT had a strong focus on vocational functioning, including functional domains required for successful work or educational outcomes, such as organization and planning, transportation and activities of daily living. Factors of clinical importance when delivering CAT with the FEP participants included cognitive heterogeneity, family involvement, flexibility in compensatory and environmental supports used, and experience of stigma. Improvements from baseline to post-intervention were observed on most measures, with the largest improvements seen in global functioning (including vocation), planning and organization, and quality of life. CONCLUSIONS: CAT is an intervention that appears well suited to addressing vocational functioning in FEP, but larger controlled trials are needed.


Assuntos
Terapia Cognitivo-Comportamental , Disfunção Cognitiva/terapia , Emprego , Transtornos Psicóticos/reabilitação , Transtornos Psicóticos/terapia , Atividades Cotidianas , Austrália , Educação , Feminino , Humanos , Masculino , Qualidade de Vida , Adulto Jovem
9.
Early Interv Psychiatry ; 10(6): 476-484, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-25496290

RESUMO

AIM: Cognitive and functioning impairments are present early in the course of psychotic disorder and remain one of the greatest treatment challenges. Cognitive adaptation training (CAT) is a compensatory approach to psychosocial intervention that is underpinned by a model that incorporates the role of cognition in daily functioning. CAT has established effectiveness in chronic schizophrenia but has received limited investigation in first-episode psychosis (FEP). The aim of this study was to examine the feasibility and acceptability of CAT in young people with FEP. METHODS: This was a single-arm feasibility study of CAT conducted at the Early Psychosis Prevention and Intervention Centre, Melbourne, Australia. Five FEP participants received manually guided CAT from a fully trained CAT therapist. A range of feasibility and acceptability measures were recorded throughout the study, including participant and case manager satisfaction ratings. RESULTS: All participants completed the CAT intervention and session attendance rates were very high (95.3%). Participants and their case managers indicated strong satisfaction with CAT as indicated by positive mean ratings on all satisfaction items, although there was a greater range in the participant ratings. Importantly, CAT did not have a negative effect on existing case management, with case managers reporting that CAT enhanced their treatment. CONCLUSIONS: This study provides evidence that CAT is a highly feasible and acceptable intervention in FEP, which may be easily integrated within existing services. The effectiveness of CAT in improving functional outcomes in FEP is worthy of investigation in a larger trial.


Assuntos
Terapia Cognitivo-Comportamental/métodos , Transtornos Psicóticos/terapia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Satisfação do Paciente , Transtornos Psicóticos/psicologia , Adulto Jovem
10.
Schizophr Res ; 150(1): 136-43, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23938175

RESUMO

AIMS: To examine whether baseline neurocognition and social cognition predict vocational outcomes over 6 months in patients with first-episode psychosis (FEP) enrolled in a randomised controlled trial of Individual Placement and Support (IPS) versus treatment as usual (TAU). METHODS: 135 FEP participants (IPS n=69; TAU n=66) completed a comprehensive neurocognitive and social cognitive battery. Principal axis factor analysis using PROMAX rotation was used to determine the underlying cognitive structure of the battery. Setwise (hierarchical) logistic and multivariate linear regressions were used to examine predictors of: (a) enrolment in education and employment; and (b) hours of employment over 6 months. Neurocognition and social cognition factors were entered into the models after accounting for premorbid IQ, baseline functioning and treatment group. RESULTS: Six cognitive factors were extracted: (i) social cognition; (ii) information processing speed; (iii) verbal learning and memory; (iv) attention and working memory; (v) visual organisation and memory; and (vi) verbal comprehension. Enrolment in education over 6 months was predicted by enrolment in education at baseline (p=.002) and poorer visual organisation and memory (p=.024). Employment over 6 months was predicted by employment at baseline (p=.041) and receiving IPS (p=.020). Better visual organisation and memory predicted total hours of paid work over 6 months (p<.001). CONCLUSIONS: Visual organisation and memory predicted the enrolment in education and duration of employment, after accounting for premorbid IQ, baseline functioning and treatment. Social cognition did not contribute to the prediction of vocational outcomes. Neurocognitive interventions may enhance employment duration in FEP.


Assuntos
Transtornos Cognitivos/etiologia , Emprego , Transtornos Psicóticos , Reabilitação Vocacional/métodos , Comportamento Social , Adolescente , Transtornos Cognitivos/reabilitação , Análise Fatorial , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Valor Preditivo dos Testes , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/complicações , Transtornos Psicóticos/psicologia , Transtornos Psicóticos/reabilitação , Adulto Jovem
11.
Crit Care ; 15(3): R153, 2011 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-21702944

RESUMO

INTRODUCTION: Acute kidney injury following surgery incurs significant mortality with no proven preventative therapy. We investigated whether the α2 adrenoceptor agonist dexmedetomidine (Dex) provides protection against ischemia-reperfusion induced kidney injury in vitro and in vivo. METHODS: In vitro, a stabilised cell line of human kidney proximal tubular cells (HK2) was exposed to culture medium deprived of oxygen and glucose. Dex decreased HK2 cell death in a dose-dependent manner, an effect attenuated by the α2 adrenoceptor antagonist atipamezole, and likely transduced by phosphatidylinositol 3-kinase (PI3K-Akt) signaling. In vivo C57BL/6J mice received Dex (25 µg/kg, intraperitoneal (i.p.)) 30 minutes before or after either bilateral renal pedicle clamping for 25 minutes or right renal pedicle clamping for 40 minutes and left nephrectomy. RESULTS: Pre- or post-treatment with Dex provided cytoprotection, improved tubular architecture and function following renal ischemia. Consistent with this cytoprotection, dexmedetomidine reduced plasma high-mobility group protein B1 (HMGB-1) elevation when given prior to or after kidney ischemia-reperfusion; pretreatment also decreased toll-like receptor 4 (TLR4) expression in tubular cells. Dex treatment provided long-term functional renoprotection, and even increased survival following nephrectomy. CONCLUSIONS: Our data suggest that Dex likely activates cell survival signal pAKT via α2 adrenoceptors to reduce cell death and HMGB1 release and subsequently inhibits TLR4 signaling to provide reno-protection.


Assuntos
Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/prevenção & controle , Dexmedetomidina/uso terapêutico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Injúria Renal Aguda/patologia , Animais , Linhagem Celular , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Substâncias Protetoras/uso terapêutico , Traumatismo por Reperfusão/patologia
12.
BMC Psychiatry ; 11: 80, 2011 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-21569382

RESUMO

BACKGROUND: Young people with first episode psychosis are at an increased risk for a range of poor health outcomes. In contrast to the growing body of evidence that suggests that exercise therapy may benefit the physical and mental health of people diagnosed with schizophrenia, there are no studies to date that have sought to extend the use of exercise therapy among patients with first episode psychosis. The aim of the study is to test the feasibility and acceptability of an exercise program that will be delivered via internet enabled mobile devices and social networking technologies among young people with first episode psychosis. METHODS/DESIGN: This study is a qualitative pilot study being conducted at Orygen Youth Health Research Centre in Melbourne, Australia. Participants are young people aged 15-24 who are receiving clinical care at a specialist first episode psychosis treatment centre. Participants will also comprise young people from the general population. The exercise intervention is a 9-week running program, designed to gradually build a person's level of fitness to be able to run 5 kilometres (3 miles) towards the end of the program. The program will be delivered via an internet enabled mobile device. Participants will be asked to post messages about their running experiences on the social networking website, and will also be asked to attend three face-to-face interviews. DISCUSSION: This paper describes the development of a qualitative study to pilot a running program coupled with the use of internet enabled mobile devices among young people with first episode psychosis. If the program is found to be feasible and acceptable to patients, it is hoped that further rigorous evaluations will ultimately lead to the introduction of exercise therapy as part of an evidence-based, multidisciplinary approach in routine clinical care.


Assuntos
Adolescente , Terapia por Exercício/psicologia , Internet , Transtornos Psicóticos/terapia , Rede Social , Terapia Assistida por Computador/métodos , Adulto Jovem , Protocolos Clínicos , Intervenção Médica Precoce/métodos , Terapia por Exercício/métodos , Feminino , Humanos , Masculino , Projetos Piloto , Transtornos Psicóticos/diagnóstico
13.
Anesthesiology ; 110(5): 1077-85, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19352168

RESUMO

BACKGROUND: Neuroapoptosis is induced by the administration of anesthetic agents to the young. As alpha2 adrenoceptor signaling plays a trophic role during development and is neuroprotective in several settings of neuronal injury, the authors investigated whether dexmedetomidine could provide functional protection against isoflurane-induced injury. METHODS: Isoflurane-induced injury was provoked in organotypic hippocampal slice cultures in vitro or in vivo in postnatal day 7 rats by a 6-h exposure to 0.75% isoflurane with or without dexmedetomidine. In vivo, the alpha2 adrenoceptor antagonist atipamezole was used to identify if dexmedetomidine neuroprotection involved alpha2 adrenoceptor activation. The gamma-amino-butyric-acid type A antagonist, gabazine, was also added to the organotypic hippocampal slice cultures in the presence of isoflurane. Apoptosis was assessed using cleaved caspase-3 immunohistochemistry. Cognitive function was assessed in vivo on postnatal day 40 using fear conditioning. RESULTS: In vivo dexmedetomidine dose-dependently prevented isoflurane-induced injury in the hippocampus, thalamus, and cortex; this neuroprotection was attenuated by treatment with atipamezole. Although anesthetic treatment did not affect the acquisition of short-term memory, isoflurane did induce long-term memory impairment. This neurocognitive deficit was prevented by administration of dexmedetomidine, which also inhibited isoflurane-induced caspase-3 expression in organotypic hippocampal slice cultures in vitro; however, gabazine did not modify this neuroapoptosis. CONCLUSION: Dexmedetomidine attenuates isoflurane-induced injury in the developing brain, providing neurocognitive protection. Isoflurane-induced injury in vitro appears to be independent of activation of the gamma-amino-butyric-acid type A receptor. If isoflurane-induced neuroapoptosis proves to be a clinical problem, administration of dexmedetomidine may be an important adjunct to prevent isoflurane-induced neurotoxicity.


Assuntos
Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/prevenção & controle , Dexmedetomidina/uso terapêutico , Isoflurano/efeitos adversos , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Transtornos Cognitivos/patologia , Dexmedetomidina/farmacologia , Isoflurano/antagonistas & inibidores , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Sprague-Dawley
14.
Neurosci Lett ; 440(3): 217-21, 2008 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-18571851

RESUMO

Xenon and other inhalational agents induce cell and organ protection through different and only partially elucidated molecular mechanisms. Anesthesia induced or pharmacologic preconditioning is a recognized mechanism of cell protection. In this study we explored the gene transcription of activity-dependent neuroprotective protein (ADNP) in neonatal rat brain as consequence to xenon exposure, comparing the noble gas to nitrogen. Seven-day-old Sprague Dawley rats were exposed for 120 min to 75% xenon and 25% oxygen or control condition consisting of 75% nitrogen and 25% oxygen (Air). ADNP was found to be differentially expressed by SSH, validated by Relative Real-Time PCR (RT-PCR) and confirmed by western blot and immunohistochemistry. The differential expression of ADNP in the rat neonatal brain may account for the preconditioning and neuroprotective effects exerted by gas xenon.


Assuntos
Anestésicos Inalatórios/farmacologia , Encéfalo/efeitos dos fármacos , Proteínas do Tecido Nervoso/metabolismo , Ativação Transcricional/efeitos dos fármacos , Xenônio/farmacologia , Animais , Animais Recém-Nascidos , Encéfalo/metabolismo , Proteínas do Tecido Nervoso/genética , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
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