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Reimbursement programmes are used to manage care through financial incentives. However, their effects are mixed and the programmes can motivate behaviour that goes against professional values. Value-based reimbursement programmes may better align professional values with financial incentives. The aim of this study is to analyse if and how healthcare providers adapt their practices to a value-based reimbursement programme that combines bundled payment with performance-based payment. Forty-one semi-structured interviews were conducted with representatives from healthcare providers within spine surgery in Sweden. Data were analysed using thematic analysis with an abductive approach and a conceptual framework based on neo-institutional theory. Healthcare providers were positive to the idea of a value-based reimbursement programme. However, during its introduction it became evident that some aspects were easier to adapt to than others. The bundled payment provided a more comprehensive picture of the patients' needs but to an increased administrative burden. Due to the financial impact of the bundled payment, healthcare providers tried to decrease the amount of post-discharge care. The performance-based payment was appreciated. However, the lack of financial impact and transparency in how the payment was calculated caused providers to neglect it. Healthcare providers adapted their practices to, but also resisted aspects of the value-based reimbursement programme. Resistance was mainly caused by lack of understanding of how to interpret and act on new information. Providers had to face unfamiliar situations, which they did not know how to handle. Better IT-facilitation and clearer definition of related care is needed to strengthen the value-based reimbursement programme among healthcare providers. A value-based reimbursement programme seems to better align professional values with financial incentives.
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Assistência ao Convalescente , Alta do Paciente , Humanos , Motivação , Instalações de Saúde , Pessoal de SaúdeRESUMO
BACKGROUND: It is crucial to provide care based on individual needs. Swedish health care is obliged to give care on equal conditions for the entire population. The person with the greatest need should be given the most care, and the health care system should strive to be cost-efficient. Medical and technical advances have been significant during the last decades and the recent Covid-19 pandemic has caused a shift in health care, from in-person visits to virtual visits. The majority of pregnant women with a low risk assessment have an uncomplicated antenatal course without adverse events. These women probably receive excessive and unnecessary antenatal care. This study will investigate if an antenatal care program for healthy pregnant women with a low risk for adverse outcomes could be safely monitored with fewer in-person visits to a midwife, and with some of them replaced by virtual visits. METHODS: This is a non-inferiority trial where a stepped wedge cluster randomized controlled design will be used. Data collection includes register data and questionnaires that concern antenatal, obstetric and neonatal outcomes, patient- and caregiver-reported experiences, healthcare-economy, and implementation aspects. The modified antenatal care (MAC) study is performed in parts of the southeast of Sweden, which has approximately 8200 childbirths annually. At the start of the study, all antenatal care centers included in the study will use the same standard antenatal care (SAC) program. In the MAC program the in-person visits to a midwife will be reduced to four instead of eight, with two additional virtual meetings compared with the SAC program. DISCUSSION: This presented study protocol is informed by research knowledge. The protocol is expected to provide a good structure for future studies on changed antenatal care programs that introduce virtual visits for healthy pregnant women with a low risk for adverse outcomes, without risking quality, safety, and increased costs. TRIAL REGISTRATION: The study is registered the 21th of April 2021 in the ISRCTN registry with trial ID: ISRCTN14422582 , retrospectively registered.
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COVID-19 , Cuidado Pré-Natal , COVID-19/prevenção & controle , Feminino , Humanos , Recém-Nascido , Pandemias , Parto , Gravidez , Gestantes , Cuidado Pré-Natal/métodos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Both polyesters and polycarbonates have been proposed as alternatives to polyethers as host materials for future polymer electrolytes for solid-state lithium-ion batteries. While being comparatively similar functional groups, the electron density on the coordinating carbonyl oxygen is different, thereby rendering different coordinating strength towards lithium ions. In this study, the transport properties of poly(ε-caprolactone) and poly(trimethylene carbonate) as well as random copolymers of systematically varied composition of the two have been investigated, in order to better elucidate the role of the coordination strength. The cationic transference number, a property well-connected with the complexing ability of the polymer, was shown to depend almost linearly on the ester content of the copolymer, increasing from 0.49 for the pure poly(ε-caprolactone) to 0.83 for pure poly(trimethylene carbonate). Contradictory to the transference number measurements that suggest a stronger lithium-to-ester coordination, DFT calculations showed that the carbonyl oxygen in the carbonate coordinates more strongly to the lithium ion than that of the ester. FT-IR measurements showed the coordination number to be higher in the polyester system, resulting in a higher total coordination strength and thereby resolving the paradox. This likely originates in properties that are specific of polymeric solvent systems, e.g. steric properties and chain dynamics, which influence the coordination chemistry. These results highlight the complexity in polymeric systems and their ion transport properties in comparison to low-molecular-weight analogues, and how polymer structure and steric effects together affect the coordination strength and transport properties.
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An amendment to this paper has been published and can be accessed via the original article.
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BACKGROUND: Value-based reimbursement programs have become increasingly common. However, little is known about the effect of such programs on patient reported outcomes. Thus, the aim of this study was to analyze the effect of introducing a value-based reimbursement program on patient reported outcome measures and to explore whether a selection bias towards less complicated patients occurred. METHODS: This is a retrospective observational study with a before and after design based on the introduction of a value-based reimbursement program in Region Stockholm, Sweden. We analyzed patient level data from inpatient and outpatient care of patients undergoing lumbar spine surgery during 2006-2015. Patient reported outcome measures used was Global Assessment, EQ-5D-3L and Oswestry Disability Index. The case-mix of surgically treated patients was analyzed using medical and socioeconomic factors. RESULTS: The value-based reimbursement program did not have any effect on targeted or non-targeted patient reported outcome measures. Moreover, the share of surgically treated patients with risk factors such as having comorbidities and being born outside of Europe increased after the introduction. Hence, the value-based reimbursement program did not encourage discrimination against sicker patients. However, the income was higher among patients surgically treated after the introduction of the value-based reimbursement. This indicates that a value-based reimbursement program may contribute to increased inequalities in access to healthcare. CONCLUSIONS: The value-based reimbursement program did not have any effect on patient reported outcome measures. Our study contributes to the understanding of the effects of a value-based reimbursement program on patient reported outcome measures and to what extent cherry-picking arises.
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Manejo da Dor , Medidas de Resultados Relatados pelo Paciente , Mecanismo de Reembolso/economia , Seguro de Saúde Baseado em Valor , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Estudos Retrospectivos , Doenças da Coluna Vertebral/complicações , Suécia , Resultado do TratamentoRESUMO
Mutations in the kinase domain of ALK (anaplastic lymphoma kinase) have recently been shown to be important for the progression of the childhood tumour neuroblastoma. In the present study we investigate six of the putative reported constitutively active ALK mutations, in positions G1128A, I1171N, F1174L, R1192P, F1245C and R1275Q. Our analyses were performed in cell-culture-based systems with both mouse and human ALK mutant variants and subsequently in a Drosophila melanogaster model system. Our investigation addressed the transforming potential of the putative gain-of-function ALK mutations as well as their signalling potential and the ability of two ATP-competitive inhibitors, Crizotinib (PF-02341066) and NVP-TAE684, to abrogate the activity of ALK. The results of the present study indicate that all mutations tested are of an activating nature and thus are implicated in tumour initiation or progression of neuroblastoma. Importantly for neuroblastoma patients, all ALK mutations used in the present study can be blocked by the inhibitors, although some mutants exhibited higher levels of drug sensitivity than others.
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Antineoplásicos/farmacologia , Mutação de Sentido Incorreto , Neuroblastoma/genética , Pirazóis/farmacologia , Piridinas/farmacologia , Pirimidinas/farmacologia , Receptores Proteína Tirosina Quinases/genética , Quinase do Linfoma Anaplásico , Animais , Animais Geneticamente Modificados , Proliferação de Células , Transformação Celular Neoplásica , Olho Composto de Artrópodes/anormalidades , Olho Composto de Artrópodes/efeitos dos fármacos , Crizotinibe , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Camundongos , Neuritos/efeitos dos fármacos , Neuroblastoma/tratamento farmacológico , Células PC12 , Fenótipo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptores Proteína Tirosina Quinases/metabolismo , Fator de Transcrição STAT3/metabolismoRESUMO
Research on solid polymer electrolytes (SPEs) is now moving beyond the realm of polyethers that have dominated the field for several decades. A promising alternative group of candidates for SPE host materials is carbonyl-containing polymers. In this work, SPE properties of three different types of carbonyl-coordinating polymers are compared: polycarbonates, polyesters, and polyketones. The investigated polymers were chosen to be as structurally similar as possible, with only the functional group being different, thereby giving direct insights into the role of the noncoordinating main-chain oxygens. As revealed by experimental measurements as well as molecular dynamics simulations, the polyketone possesses the lowest glass transition temperature, but the ion transport is limited by a high degree of crystallinity. The polycarbonate, on the other hand, displays a relatively low coordination strength but is instead limited by its low molecular flexibility. The polyester performs generally as an intermediate between the other two, which is reasonable when considering its structural relation to the alternatives. This work demonstrates that local changes in the coordinating environment of carbonyl-containing polymers can have a large effect on the overall ion conduction, thereby also showing that desired transport properties can be achieved by fine-tuning the polymer chemistry of carbonyl-containing systems.
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BACKGROUND: Stress-related ill health, e.g. burnout, is of great concern worldwide. Effective rehabilitation programs need to be developed and their therapeutic aspects understood. PURPOSE: To explore and describe how women with stress-related ill health who are on sick leave experience the rehabilitation process in a therapeutic garden and how these experiences connect to their everyday lives. METHODS: This longitudinal study used methods from grounded theory. Five women completed three semi-structured interviews at three weekly intervals during rehabilitation and one interview three months after. Data were analyzed using a constant comparative approach. FINDINGS: A secure environment facilitated engagement in activities that provided feelings of enjoyment. These experiences inspired participants to add enjoyable activities in their everyday lives, contributing to occupational balance, despite worries of not be able to continue performing enjoyable activities. Implications. Effective rehabilitation programs need to focus on enjoyable activities in a protective environment to support achievement of occupational balance.
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Esgotamento Profissional/reabilitação , Jardinagem , Adulto , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Licença MédicaRESUMO
PURPOSE: Using financial incentives has been criticised for putting too much focus on things that can be measured. Value-based reimbursement may better align professional values with financial incentives. However, professional values may differ between actor groups. In this article, the authors identify institutional logics within healthcare-providing organisations. Further, the authors analyse how the centrality and compatibility of the identified logics affect the institutionalisation of external demands. DESIGN/METHODOLOGY/APPROACH: 41 semi-structured interviews were conducted with representatives from healthcare providers within spine surgery in Sweden, where a value-based reimbursement programme was introduced. Data were analysed using thematic content analysis with an abductive approach, and a conceptual framework based on neo-institutional theory. FINDINGS: After the introduction of the value-based reimbursement programme, the centrality and compatibility of the institutional logics within healthcare-providing organisations changed. The logic of spine surgeons was dominating whereas physiotherapists struggled to motivate a higher cost for high quality physiotherapy. The institutional logic of nurses was aligned with spine surgeons, however as a peripheral logic facilitating spine surgery. To attain holistic and interdisciplinary healthcare, dominating institutional logics within healthcare-providing organisations need to allow peripheral institutional logics to attain a higher centrality for higher compatibility. Thus, allowing other occupations to take responsibility for quality and attain the feeling of professional pride. ORIGINALITY/VALUE: Interviewing spine surgeons, physiotherapists, nurses, managers and administrators allows us to deepen the understanding of micro-level behaviour as a reaction (or lack thereof) to macro-level decisions.
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Pessoal Administrativo , Instalações de Saúde , Pessoal de Saúde , Humanos , Lógica , MotivaçãoRESUMO
BACKGROUND: In Drosophila muscle cell fusion takes place both during the formation of the somatic mesoderm and the visceral mesoderm, giving rise to the skeletal muscles and the gut musculature respectively. The core process of myoblast fusion is believed to be similar for both organs. The actin cytoskeleton regulator Verprolin acts by binding to WASP, which in turn binds to the Arp2/3 complex and thus activates actin polymerization. While Verprolin has been shown to be important for somatic muscle cell fusion, the function of this protein in visceral muscle fusion has not been determined. RESULTS: Verprolin is specifically expressed in the fusion competent myoblasts of the visceral mesoderm, suggesting a role in visceral mesoderm fusion. We here describe a novel Verprolin mutant allele which displays subtle visceral mesoderm fusion defects in the form of mislocalization of the immunoglobulin superfamily molecule Duf/Kirre, which is required on the myoblast cell surface to facilitate attachment between cells that are about to fuse, indicating a function for Verprolin in visceral mesoderm fusion. We further show that Verprolin mutant cells are capable of both migrating and fusing and that the WASP-binding domain of Verprolin is required for rescue of the Verprolin mutant phenotype. CONCLUSIONS: Verprolin is expressed in the visceral mesoderm and plays a role in visceral muscle fusion as shown by mislocalization of Duf/Kirre in the Verprolin mutant, however it is not absolutely required for myoblast fusion in either the visceral or the somatic mesoderm.
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Fusão Celular , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/citologia , Drosophila melanogaster/embriologia , Animais , Proteínas de Drosophila/genética , Drosophila melanogaster/metabolismo , Mesoderma , Músculo Liso/embriologia , Mioblastos/metabolismo , Família de Proteínas da Síndrome de Wiskott-Aldrich/metabolismoAssuntos
Custos de Cuidados de Saúde , Neoplasias Cutâneas/economia , Neoplasias Cutâneas/terapia , Absenteísmo , Assistência Ambulatorial/economia , Eficiência , Custos Hospitalares , Humanos , Atenção Primária à Saúde/economia , Aposentadoria/economia , Licença Médica/economia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/mortalidade , Suécia/epidemiologia , Fatores de TempoRESUMO
Increasing the ionic conductivity has for decades been an overriding goal in the development of solid polymer electrolytes. According to fundamental theories on ion transport mechanisms in polymers, the ionic conductivity is strongly correlated to free volume and segmental mobility of the polymer for the conventional transport processes. Therefore, incorporating plasticizing side chains onto the main chain of the polymer host often appears as a clear-cut strategy to improve the ionic conductivity of the system through lowering of the glass transition temperature (T g). This intended correlation between T g and ionic conductivity is, however, not consistently observed in practice. The aim of this study is therefore to elucidate this interplay between segmental mobility and polymer structure in polymer electrolyte systems comprising plasticizing side chains. To this end, we utilize the synthetic versatility of the ion-conductive poly(trimethylene carbonate) (PTMC) platform. Two types of host polymers with side chains added to a PTMC backbone are employed, and the resulting electrolytes are investigated together with the side chain-free analogue both by experiment and with molecular dynamics (MD) simulations. The results show that while added side chains do indeed lead to a lower T g, the total ionic conductivity is highest in the host matrix without side chains. It was seen in the MD simulations that while side chains promote ionic mobility associated with the polymer chain, the more efficient interchain hopping transport mechanism occurs with a higher probability in the system without side chains. This is connected to a significantly higher solvation site diversity for the Li+ ions in the side-chain-free system, providing better conduction paths. These results strongly indicate that the side chains in fact restrict the mobility of the Li+ ions in the polymer hosts.
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Cholinergic and GABAergic neurons in the medial septum/vertical limb of the diagonal band of Broca (MS/vDB) projecting to the hippocampus, constitute the septohippocampal projection, which is important for hippocampal-dependent learning and memory. There is also evidence for an extrinsic as well as an intrinsic glutamatergic network within the MS/vDB. GABAergic and cholinergic septohippocampal neurons express the serotonergic 5-HT(1A) receptor and most likely also glutamatergic NMDA receptors. The aim of the present study was to examine whether septal 5-HT(1A) receptors are important for hippocampal-dependent long-term memory and whether these receptors interact with glutamatergic NMDA receptor transmission in a manner important for hippocampal-dependent spatial memory. Intraseptal infusion of the 5-HT(1A) receptor agonist (R)-8-OH-DPAT (1 or 4 microg/rat) did not affect spatial learning in the water maze task but impaired emotional memory in the passive avoidance task at the higher dose tested (4 microg/rat). While intraseptal administration of (R)-8-OH-DPAT (4 microg) combined with a subthreshold dose of the NMDA receptor antagonist D-AP5 (1 microg) only marginally affected spatial acquisition, it produced a profound impairment in spatial memory. In conclusion, septal 5-HT(1A) receptors appears to play a more prominent role in emotional than in spatial memory. Importantly, septal 5-HT(1A) and NMDA receptors appear to interact in a manner, which is particularly critical for the expression or retrieval of hippocampal-dependent long-term spatial memory. It is proposed that NMDA receptor hypofunction in the septal area may unmask a negative effect of 5-HT(1A) receptor activation on memory, which may be clinically relevant.
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Hipocampo/fisiologia , Aprendizagem/fisiologia , Receptor 5-HT1A de Serotonina/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Septo do Cérebro/fisiologia , Percepção Espacial/fisiologia , 2-Amino-5-fosfonovalerato/farmacologia , 8-Hidroxi-2-(di-n-propilamino)tetralina/administração & dosagem , 8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem da Esquiva/fisiologia , Relação Dose-Resposta a Droga , Emoções/efeitos dos fármacos , Emoções/fisiologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Aprendizagem/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Memória/efeitos dos fármacos , Memória/fisiologia , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Septo do Cérebro/efeitos dos fármacos , Agonistas do Receptor 5-HT1 de Serotonina , Agonistas do Receptor de Serotonina/administração & dosagem , Agonistas do Receptor de Serotonina/farmacologia , Percepção Espacial/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/fisiologia , Fatores de TempoRESUMO
Caffeine is believed to exert its stimulant effects by blocking A(2A) and A(1) adenosine receptors (A(2A)R and A(1)R). Although a genetic knockout of A(2A)R eliminates effects of caffeine, the phenotype of the knockout animal does not resemble that of caffeine treatment. In this study we explored the possibility that a mere reduction of the number of A(1)Rs and A(2A)Rs, achieved by deleting one of the two copies of the A(1)R and A(2A)R genes, would mimic some aspects of long-term caffeine ingestion. The A(1)R and A(2A)R double heterozygous (A(1)R-A(2A)R dHz) mice indeed had approximately one-half the number of A(1)R and A(2A)R, and there were little compensatory changes in A(2B) or A(3) adenosine receptor (A(2B)R or A(3)R) expression. The ability of a stable adenosine analog to activate receptors was shifted to the right by caffeine and in A(1)R-A(2A)R dHz tissue. Caffeine (0.3 g/l in drinking water for 7-10 days) and A(1)R-A(2A)R dHz genotype increased locomotor activity (LA) and decreased heart rate without significantly influencing body temperature. The acute stimulatory effect of a single injection of caffeine was reduced in A(1)R-A(2A)R dHz mice and in mice treated long term with oral caffeine. Thus at least some aspects of long-term caffeine use can be mimicked by genetic manipulation of the A(1)R and A(2A)R.
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Cafeína/administração & dosagem , Estimulantes do Sistema Nervoso Central/administração & dosagem , Receptor A1 de Adenosina/metabolismo , Receptores A2 de Adenosina/metabolismo , Antagonistas do Receptor A1 de Adenosina , Antagonistas do Receptor A2 de Adenosina , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Administração Oral , Animais , Temperatura Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Genótipo , Frequência Cardíaca/efeitos dos fármacos , Heterozigoto , Injeções Intraperitoneais , Lipólise/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Atividade Motora/efeitos dos fármacos , Fenótipo , Receptor A1 de Adenosina/deficiência , Receptor A1 de Adenosina/genética , Receptores A2 de Adenosina/deficiência , Receptores A2 de Adenosina/genética , Fatores de TempoRESUMO
Serotonergic (5-HT) neurotransmission plays a role in learning and memory processes, but the physiological role of various receptor subtypes is not well characterised. Among these, 5-HT(1B) receptors are located as autoreceptors on 5-HT axons and heteroreceptors on non-serotonergic terminals. This study examined the role of the 5-HT(1B) receptor in one-trial aversive contextual learning using the passive avoidance (PA) task in NMRI mice. Subcutaneous administration of the 5-HT(1B) receptor agonist anpirtoline (0.1-1.0mg/kg) before PA training impaired retention performance 24h later. Combined administration of anpirtoline with the selective 5-HT(1B) receptor antagonist NAS-181 (0.1-1.0mg/kg) fully blocked the impairments. Administration of NAS-181 alone dose-dependently improved PA retention performance. This facilitatory effect was blocked by subthreshold doses of both the muscarinic antagonist scopolamine (0.03 mg/kg) and the NMDA receptor antagonist MK-801 (0.03 mg/kg). NAS-181 also fully blocked the PA impairments induced by an amnesic dose of scopolamine (0.1mg/kg), when administered prior to, but not after, scopolamine. In addition, NAS-181 attenuated PA impairments induced by MK-801 (0.3mg/kg). These findings indicate that 5-HT(1B) receptors are activated at basal levels of 5-HT transmission. The facilitatory effect of NAS-181 involved alleviation of an inhibitory 5-HT tone mediated via 5-HT(1B) receptors on cholinergic and glutamatergic transmission. This disinhibition is expected to occur in neuronal circuits involved in contextual learning including the hippocampus and interconnected cortico-limbic regions. Blockade of brain 5-HT(1B) heteroreceptors may represent a novel therapeutic strategy for restoration of deficient cholinergic and glutamatergic neurotransmission contributing to memory disorders.
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Acetilcolina/metabolismo , Aprendizagem da Esquiva/fisiologia , Ácido Glutâmico/metabolismo , Receptor 5-HT1B de Serotonina/fisiologia , Transmissão Sináptica/fisiologia , Análise de Variância , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Benzopiranos/farmacologia , Antagonistas Colinérgicos/farmacologia , Maleato de Dizocilpina/farmacologia , Relação Dose-Resposta a Droga , Antagonistas de Aminoácidos Excitatórios/farmacologia , Masculino , Camundongos , Morfolinas/farmacologia , Piperidinas/farmacologia , Piridinas/farmacologia , Tempo de Reação/efeitos dos fármacos , Escopolamina/farmacologia , Antagonistas da Serotonina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Transmissão Sináptica/efeitos dos fármacosRESUMO
The principal 5-HT(1A) receptor agonist 8-Hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT) impairs several different types of learning. Besides 5-HT(1A) receptors, 8-OH-DPAT stimulates 5-HT(7) receptors, but it is not known whether 5-HT(7) receptors contribute to the impairments. The 5-HT(7) receptor antagonist (2R)-1-[(3-Hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl] pyrrolidine (SB-269970) was combined with 8-OH-DPAT to dissociate 5-HT(1A) from 5-HT(7) receptor-mediated effects, in the passive avoidance task for emotional learning. SB-269970 intensified impairments caused by 8-OH-DPAT. SB-269970 alone had no effect on memory performance, but moderately decreased retention under suboptimal learning conditions. These findings indicate that 5-HT(7) receptor stimulation by 8-OH-DPAT counteracts 5-HT(1A) receptor-mediated impairments in hippocampal-dependent contextual learning.
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8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Aprendizagem da Esquiva/efeitos dos fármacos , Receptores de Serotonina/fisiologia , Agonistas do Receptor 5-HT1 de Serotonina , Agonistas do Receptor de Serotonina/farmacologia , Animais , Hipocampo/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
We have examined behavioral consequences of genetic deletion of the adenosine A3 receptors in mice. The open field behavior of A3 adenosine receptor knock-out (A3R KO) mice was investigated both under basal conditions and after stimulation with psychostimulants. Adolescent (21 day-old) and adult A3R KO males showed an increase in overall motor activity compared to wild type (WT) males, but the type of activity differed. The motor activity, especially rearing, was also higher in A3R KO compared to WT adult females. A3 receptors have a low affinity for caffeine and it was therefore surprising to find a decreased response to stimulation with either caffeine or amphetamine in A3R KO as compared to WT mice in males as well as females. Telemetry recordings also showed a significantly smaller increase in activity upon darkness in A3R KO. There were no compensatory changes in the mRNA expression of any other adenosine receptor subtypes (A1, A2A and A2B) or any changes in dopamine D1 and D2 receptor binding in A3R KO brains. Challenge with the developmental toxicant methylmercury (1 microM in drinking water) during pregnancy and lactation did not cause any behavioral alterations in adolescent and adult WT female offspring. In contrast, the A3R KO female offspring displayed changes in locomotion indicating an interaction between perinatal methylmercury and adenosine A3 receptors. In conclusion, despite low expression of A3 receptors in wild type mouse brain we observed several behavioral consequences of genetic elimination of the adenosine A3 receptors. The possibility that this is due to a role of A3 receptors in development is discussed.
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Cafeína/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Comportamento Exploratório/fisiologia , Atividade Motora/efeitos dos fármacos , Receptor A3 de Adenosina/fisiologia , Anfetamina/farmacologia , Análise de Variância , Animais , Escuridão , Poluentes Ambientais/toxicidade , Comportamento Exploratório/efeitos dos fármacos , Feminino , Masculino , Compostos de Metilmercúrio/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Atividade Motora/genética , Neurotoxinas/toxicidade , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Receptor A3 de Adenosina/efeitos dos fármacos , Receptor A3 de Adenosina/genética , Receptores Dopaminérgicos/classificação , Receptores Dopaminérgicos/efeitos dos fármacos , Receptores Dopaminérgicos/metabolismo , Fatores Sexuais , Estatísticas não ParamétricasRESUMO
Melanophores from Xenopus laevis are pigmented cells, capable of quick colour changes through cyclic adenosine 3':5'-monophosphate (cAMP) coordinated transport of their intracellular pigment granules, melanosomes. In this study we use the melanophore cell line to evaluate the effects of Panax ginseng extract G115 on organelle transport. Absorbance readings of melanophore-coated microplates, Correlate-EIA direct cAMP enzyme immunoassay kit, and western blot were used to measure the melanosome movement and changes in intracellular signalling. We show that Panax ginseng induces a fast concentration-dependent anterograde transport of the melanosomes. No significant increase in the cAMP level was seen and pre-incubation of melanophores with the protein kinase C (PKC) inhibitor EGF-R Fragment 651-658 (M-EGF) only partly decreased the ginseng-induced dispersion. We also demonstrate that Panax ginseng, endothelin-3 (ET-3) and alpha-melanocyte stimulating hormone (MSH) stimulate an activation of mitogen activated protein kinase (MAPK). Pre-incubation with M-EGF decreased the MAPK activity induced by ET-3 and MSH, but again only marginally affected the response of Panax ginseng. Thus, in melanophores we suggest that Panax ginseng stimulates an anterograde transport of pigment organelles via a non-cAMP and mainly PKC-independent pathway.
Assuntos
Organelas/efeitos dos fármacos , Panax/química , Pigmentos Biológicos/metabolismo , Extratos Vegetais/farmacologia , Animais , Transporte Biológico/efeitos dos fármacos , Western Blotting , AMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , Endotelina-3/farmacologia , Técnicas Imunoenzimáticas/métodos , Melanóforos/efeitos dos fármacos , Melanóforos/metabolismo , Organelas/metabolismo , Extratos Vegetais/administração & dosagem , Proteína Quinase C/efeitos dos fármacos , Proteína Quinase C/metabolismo , Transdução de Sinais/efeitos dos fármacos , Xenopus laevis , alfa-MSH/farmacologiaRESUMO
BACKGROUND: HBV-DNA quantitation, the HBe antigen status and the appearance of mutations in the core promoter, precore and polymerase regions are important elements in the management of chronic HBV infection. METHODS: We performed a technical evaluation of 3 new kits, affigene HBV VL, affigene HBV mutant VL and affigene HBV DE/3TC assays (Sangtec Molecular Diagnostics) in comparison with the Amplicor HBV Monitor assay (Manual Test, Roche), direct sequencing and direct sequencing/Inno-LIPA HBV DR (Innogenetics), respectively. We evaluated the clinical application of these tests in the management of patients with chronic (HBeAg positive) hepatitis B. Serial sera of 11 chronic HBeAg positive patients were studied before, during and after lamivudine/interferon treatment. RESULTS: HBV-DNA quantitation detected with affigene HBV VL showed a high correlation with the Amplicor HBV Monitor test (r=0.85). affigene HBV mutant VL (positions G1764A, G1896A) and affigene HBV DE/3TC (positions rtL180M, rtM204V/I) were able to detect a low presence of mutants in a mixed population (wild type and mutant) compared to direct sequencing and Inno-LIPA HBV DR, which identified only the dominant population. CONCLUSIONS: These three sensitive assays, performed with the same DNA extraction, give clinicians useful information for the management of chronic hepatitis B and for timing treatment.
Assuntos
DNA Viral/sangue , DNA Polimerase Dirigida por DNA/genética , Antígenos do Núcleo do Vírus da Hepatite B/genética , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Reação em Cadeia da Polimerase/métodos , Kit de Reagentes para Diagnóstico , Adolescente , Adulto , Antivirais/uso terapêutico , Criança , Sistemas Computacionais , Análise Mutacional de DNA , DNA Viral/genética , Feminino , Genes Virais , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/sangue , Hepatite B Crônica/tratamento farmacológico , Humanos , Interferon-alfa/uso terapêutico , Lamivudina/uso terapêutico , Masculino , Mutação de Sentido Incorreto/genética , Mutação Puntual/genética , Regiões Promotoras Genéticas/genética , Inibidores da Transcriptase Reversa/uso terapêutico , Sensibilidade e Especificidade , Análise de Sequência de DNA , Carga ViralRESUMO
Neurogenesis in the dentate gyrus (DG) of the adult hippocampus is a process regulated by experience. To understand whether experience also modifies the connectivity of new neurons, we systematically investigated changes in their innervation following environmental enrichment (EE). We found that EE exposure between 2-6 weeks following neuron birth, rather than merely increasing the number of new neurons, profoundly affected their pattern of monosynaptic inputs. Both local innervation by interneurons and to even greater degree long-distance innervation by cortical neurons were markedly enhanced. Furthermore, following EE, new neurons received inputs from CA3 and CA1 inhibitory neurons that were rarely observed under control conditions. While EE-induced changes in inhibitory innervation were largely transient, cortical innervation remained increased after returning animals to control conditions. Our findings demonstrate an unprecedented experience-dependent reorganization of connections impinging onto adult-born neurons, which is likely to have important impact on their contribution to hippocampal information processing.