RESUMO
Serotonin acts through its receptors (5-HTRs) to shape brain networks during development and modulates essential functions in mature brain. The 5-HT1AR is mainly located at soma of hippocampal neurons early during brain development and its expression gradually shifts to dendrites during postnatal development. The 5-HT7R expressed early during hippocampus development, shows a progressive reduction in its expression postnatally. Considering these changes during development, we evaluated in cultured hippocampal neurons whether the 5-HT1AR and 5-HT7R change their expression, modulate dendritic growth, and activate signaling pathways such as ERK1/2, AKT/GSK3ß and LIMK/cofilin, which may sustain dendrite outgrowth by controlling cytoskeleton dynamics. We show that mRNA levels of both receptors increase between 2 and 7 DIV; however only protein levels of 5-HT7R increase significantly at 7 DIV. The 5-HT1AR is preferentially distributed in the soma, while 5-HT7R displays a somato-dendritic localization at 7 DIV. Through stimulation with 5-HT at 7 DIV during 24h and using specific antagonists, we determined that 5-HT1AR decreases the number of primary and secondary dendrites and restricts the growth of primary dendrites. The activation of 5-HT1AR and 5-HT7R promotes the growth of short secondary dendrites and triggers ERK1/2 and AKT phosphorylation through MEK and PI3K activation respectively; without changes in the phosphorylation of LIMK and cofilin. We conclude that 5-HT1AR restricts dendritogenesis and outgrowth of primary dendrites, but that both 5-HT1AR and 5-HT7R promote secondary dendrite outgrowth. These data support the role of 5-HT in neuronal outgrowth during development and provide insight into cellular basis of neurodevelopmental disorders.
Assuntos
Dendritos/efeitos dos fármacos , Dendritos/metabolismo , Receptor 5-HT1A de Serotonina/metabolismo , Receptores de Serotonina/metabolismo , Serotonina/farmacologia , Animais , Células Cultivadas , Hipocampo/metabolismo , Neurogênese/fisiologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
The risk for neuropsychiatric illnesses has a strong sex bias, and for major depressive disorder (MDD), females show a more than 2-fold greater risk compared to males. Such mood disorders are commonly associated with a dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis. Thus, sex differences in the incidence of MDD may be related with the levels of gonadal steroid hormone in adulthood or during early development as well as with the sex differences in HPA axis function. In rodents, organizational and activational effects of gonadal steroid hormones have been described for the regulation of HPA axis function and, if consistent with humans, this may underlie the increased risk of mood disorders in women. Other developmental factors, such as prenatal stress and prenatal overexposure to glucocorticoids can also impact behaviors and neuroendocrine responses to stress in adulthood and these effects are also reported to occur with sex differences. Similarly, in humans, the clinical benefits of antidepressants are associated with the normalization of the dysregulated HPA axis, and genetic polymorphisms have been found in some genes involved in controlling the stress response. This review examines some potential factors contributing to the sex difference in the risk of affective disorders with a focus on adrenal and gonadal hormones as potential modulators. Genetic and environmental factors that contribute to individual risk for affective disorders are also described. Ultimately, future treatment strategies for depression should consider all of these biological elements in their design.
Assuntos
Corticosteroides/metabolismo , Hormônios Gonadais/metabolismo , Transtornos do Humor/complicações , Transtornos do Humor/metabolismo , Caracteres Sexuais , Estresse Psicológico/complicações , Estresse Psicológico/metabolismo , Antidepressivos/uso terapêutico , Feminino , Humanos , Masculino , Transtornos do Humor/tratamento farmacológico , Estresse Psicológico/tratamento farmacológicoRESUMO
Asphyxia during delivery produces long-term deficits in brain development, including hippocampus. We investigated hippocampal plasticity after perinatal asphyxia, measuring postnatal apoptosis and neurogenesis. Asphyxia was performed by immersing rat fetuses with uterine horns removed from ready-to-deliver rats into a water bath for 20 min. Caesarean-delivered pups were used as controls. The animals were euthanized 1 week or 1 month after birth. Apoptotic nuclear morphology and DNA breaks were assessed by Hoechst and TUNEL assays. Neurogenesis was estimated by bromodeoxyuridine/MAP-2 immunocytochemistry, and the levels and expression of proteins related to apoptosis and cell proliferation were measured by Western blots and in situ hybridization, respectively. There was an increase of apoptosis in CA1, CA3, and dentate gyrus (DG) and cell proliferation and neurogenesis in CA1, DG, and hilus regions of hippocampus 1 week after asphyxia. The increase of apoptosis in CA3 and cell proliferation in the suprapyramidal band of DG was still observed 1 month following asphyxia. There was an increase of BAD, BCL-2, ERK2, and bFGF levels in whole hippocampus and bFGF expression in CA1 and CA2 and hilus at P7 and P30. There was a concomitant decrease of phosphorylated-BAD (Ser112) levels. The increase of BAD levels supports the idea of delayed cell death after perinatal asphyxia, whereas the increases of BCL-2, ERK2, and bFGF levels suggest the activation of neuroprotective and repair pathways. In conclusion, perinatal asphyxia induces short- and long-term regionally specific plastic changes, including delayed cell death and neurogenesis, involving pro- and antiapoptotic as well as mitogenic proteins, favoring hippocampal functional recovery.
Assuntos
Animais Recém-Nascidos/fisiologia , Apoptose/fisiologia , Asfixia/patologia , Diferenciação Celular/fisiologia , Hipocampo/fisiologia , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia , Animais , Animais Recém-Nascidos/anatomia & histologia , Asfixia/genética , Asfixia/metabolismo , Proliferação de Células , Feminino , Hipocampo/citologia , Neurônios/citologia , Gravidez , Ratos , Ratos WistarRESUMO
A form of polycystic ovary (PCO) resembling some aspects of the human PCO syndrome can be induced in rats by a single injection of estradiol valerate (EV). An increase in sympathetic outflow to the ovary precedes, by several weeks, the appearance of cysts, suggesting the involvement of a neurogenic component in the pathology of this ovarian dysfunction. The present study was carried out to test the hypotheses that this change in sympathetic tone is related to an augmented production of ovarian nerve growth factor (NGF), and that this abnormally elevated production of NGF contributes to the formation of ovarian cysts induced by EV. Injection of the steroid resulted in increased intraovarian synthesis of NGF and its low affinity receptor, p75 NGFR. The increase was maximal 30 days after EV, coinciding with the elevation in sympathetic tone to the ovary and preceding the appearance of follicular cysts. Intraovarian injections of the retrograde tracer fluorogold combined with in situ hybridization to detect tyrosine hydroxylase (TH) messenger RNA-containing neurons in the celiac ganglion revealed that these changes in NGF/p75 NGFR synthesis are accompanied by selective activation of noradrenergic neurons projecting to the ovary. The levels of RBT2 messenger RNA, which encodes a beta-tubulin presumably involved in slow axonal transport, were markedly elevated, indicating that EV-induced formation of ovarian cysts is preceded by functional activation ofceliac ganglion neurons, including those innervating the ovary. Intraovarian administration of a neutralizing antiserum to NGF in conjunction with an antisense oligodeoxynucleotide to p75 NGFR, via Alzet osmotic minipumps, restored estrous cyclicity and ovulatory capacity in a majority of EV-treated rats. These functional changes were accompanied by restoration of the number of antral follicles per ovary that had been depleted by EV and a significant reduction in the number of both precystic follicles and follicular cysts. The results indicate that the hyperactivation of ovarian sympathetic nerves seen in EV-induced PCO is related to an overproduction of NGF and its low affinity receptor in the gland. They also suggest that activation of this neurotrophic-neurogenic regulatory loop is a component of the pathological process by which EV induces cyst formation and anovulation in rodents. The possibility exists that a similar alteration in neurotrophic input to the ovary contributes to the etiology and/or maintenance of the PCO syndrome in humans.
Assuntos
Estradiol/análogos & derivados , Estrogênios Conjugados (USP)/toxicidade , Fatores de Crescimento Neural/biossíntese , Ovário/metabolismo , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/metabolismo , Receptores de Fator de Crescimento Neural/biossíntese , Animais , Anticorpos Bloqueadores/farmacologia , Reagentes de Ligações Cruzadas , Estradiol/toxicidade , Feminino , Imuno-Histoquímica , Hibridização In Situ , Fatores de Crescimento Neural/antagonistas & inibidores , Fatores de Crescimento Neural/imunologia , Norepinefrina/fisiologia , Oligodesoxirribonucleotídeos Antissenso/farmacologia , Ovário/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptores de Fator de Crescimento Neural/antagonistas & inibidores , Ribonucleases/metabolismo , Sistema Nervoso Simpático/fisiologia , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
Depolarization of the synaptosomal membrane by a rapid elevation of [K+]0 induces secretion of adenosine-5'-triphosphate (ATP) as well as the specific neurotransmitters. In addition to the classical [Ca2+]0-dependent mode, we have found that ATP secretion also occurred in the absence of extracellular calcium [( Ca2+]0 less than 1 microM). The extent of both modalities of secretion depended on membrane potential, and the [Ca2+]0-independent secretion proceeded at a rate that was substantially smaller than that of the [Ca2+]0-dependent mode at all membrane potentials examined. We propose that intracellular stores may provide the Ca2+ required for exocytosis in the [Ca2+]0-independent mode of ATP secretion. To test this hypothesis, we searched for the presence of Ca(2+)-release channels gated by intracellular messengers in our synaptosomal preparation. We fused membrane vesicles from lysed synaptosomes with acidic phospholipid bilayers formed at the tip of a patch pipette and found that these membranes contained a Ca(2+)-selective channel. The properties of this channel resemble those of the Ca(2+)-release channel reconstituted from sarcoplasmic reticulum membrane vesicles. These include size of the single open-channel conductance (75 pS Cs+ as the main current carrier), activation by adenine nucleotides (ATP), ryanodine and caffeine, and inhibition by ruthenium red.
Assuntos
Cálcio/metabolismo , Retículo Endoplasmático/metabolismo , Neurotransmissores/metabolismo , Animais , Cálcio/farmacologia , Canais de Cálcio/fisiologia , Potenciais da Membrana/fisiologiaRESUMO
The trisomy-16 (TS16) mouse is considered to be a model of human trisomy 21 (Down syndrome) because of genetic homology between mouse chromosome 16 and human chromosome 21. We examined cholinergic function of brain and spinal cord tissue and in cultured neurons from TS16 mouse compared with that of age matched controls. Mean acetylcholinesterase activity in both tissue types did not differ between trisomic and control conditions. Acetylcholine (ACh) synthesis, measured as choline O-acetyltratransferase (acetyl-CoA) activity, was reduced to 67% of control in TS16 brain but not in TS16 spinal cord. Steady-state accumulation of ACh precursor, [3H]choline, was measured in primary cell cultures. Steady-state choline uptake was reduced to 35% and to 61% in neurons of TS16 brain and spinal cord, respectively, when compared with controls. Kinetics experiments in TS16 brain cells showed a 50% reduction of the maximal velocity of choline uptake when compared to controls. Further, the ACh release induced by KCl depolarization in TS16 spinal cord neurons did not differ from control neurons but was reduced in TS16 brain neurons. This effect cannot be explained solely by a reduction in ACh synthesis. The results indicate that the TS16 condition in mice significantly modified the cholinergic function in brain, and to a lesser degree in spinal cord, suggesting that the higher gene dosage inherent to the trisomic condition affects cholinergic neurons in different regions of the central nervous system in a differential fashion.
Assuntos
Acetilcolina/fisiologia , Sistema Nervoso Central/fisiopatologia , Síndrome de Down/fisiopatologia , Neurônios/fisiologia , Trissomia , Acetilcolinesterase/metabolismo , Animais , Células Cultivadas , Sistema Nervoso Central/patologia , Colina/metabolismo , Modelos Animais de Doenças , Humanos , Masculino , CamundongosRESUMO
It has previously been shown that adrenalectomy (ADX) produces apoptosis in the granule cell of the dentate gyrus (DG), and that this effect is prevented by corticosterone replacement. Thus, we have investigated how this phenomenon takes place in rat hippocampus using in situ hybridization. The expression of the pro-apoptotic gene bax was measured in the pyramidal cell fields and in the DG. After 5 days of ADX, there was a significant increase in bax mRNA levels in the suprapyramidal layer of the DG, an effect prevented by corticosterone replacement. The mRNA of the anti-apoptotic bcl-2 gene was expressed in CA3 and DG. ADX increased bcl-2 mRNA levels, but only in the suprapyramidal layer of the DG, an effect that was prevented by corticosterone administration. It is concluded that the up-regulation of bax may explain the apoptosis observed in DG after ADX, while the bcl-2 induction may correspond to a compensatory mechanism protecting the cells from death.
Assuntos
Anti-Inflamatórios/farmacologia , Corticosterona/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Genes bcl-2/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Adrenalectomia , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Corticosterona/genética , Giro Denteado/efeitos dos fármacos , Giro Denteado/metabolismo , Hipocampo/metabolismo , Masculino , Proteínas Proto-Oncogênicas/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/efeitos dos fármacos , Células Piramidais/efeitos dos fármacos , Células Piramidais/metabolismo , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Proteína X Associada a bcl-2 , Proteína bcl-XRESUMO
Since the early 1980s, the Ministries of Health of most Developing Countries have been plagued by significant and persistent resource shortages. One response of many Third World countries to this health financing crisis has been to turn to user fees. This article presents a case study of the evolution of public health care system fees in El Salvador in the decade of the 1980s. Since 1980 falling levels of real funding of the Ministry of Health of El Salvador have resulted in falling supplies of drugs, materials and equipment throughout the public health system, and have contributed to declining utilization levels of public health facilities. Local public health providers and their community health boards (patronatos) have responded to this crisis by creatively institutionalizing decentralized, revolving accounts based on 'voluntary' user fees for ambulatory care, collected and retained at individual facilities. This article describes the legal foundations, organization, functioning, incentive structures, financial performance, and the institutional development of El Salvador's local user fee systems.
Assuntos
Serviços de Saúde Comunitária/economia , Honorários Médicos , Saúde Pública/economia , El Salvador , Órgãos Governamentais/economia , Gastos em Saúde , Humanos , GuerraRESUMO
This study analyzes the causes and effects of the persistent underfinancing of recurrent costs in the Ministry of Health (MOH) of El Salvador over the past decade. Causative factors identified and discussed include (1) a functionally unintegrated MOH structure--consisting of (a) the autonomous hospitals and (b) the remainder of the Ministry; (2) the functional isolation of the Ministry's planning department from its budgetary department; (3) the use of historical-budget based decision-making--in lieu of more explicitly goal oriented resource allocation and planning criteria; (4) donor agencies' funding of infrastructure construction projects, coupled with their unwillingness to financially support the recurrent costs such projects ultimately give rise to; and finally, (5) the civil war and its associated economic dislocation, altered central government funding priorities and general state of disarray. The effects of persistent underfinancing of recurrent costs in El Salvador are the growing proportion of the MOH budget being consumed by outlays for personnel at the expense of virtually all other budgetary categories; the shortages of drugs and general medical supplies in public health facilities; and reduced levels of utilization of those facilities from what would otherwise be expected; all of which together imply a reduced level of both productivity and effectiveness of the public health care system. Policy implications and recommendations are briefly noted.
Assuntos
Atenção à Saúde/economia , Órgãos Governamentais/organização & administração , Saúde Pública/economia , Orçamentos , El Salvador , Apoio ao Planejamento em Saúde , Recursos em Saúde/provisão & distribuição , Cooperação Internacional , Regionalização da Saúde/organização & administração , GuerraRESUMO
Ignorance about the costs, case loads and case mixes of different hospitals within the public health system constitutes an important obstacle to reforming health care spending in many developing countries. National (tertiary) hospitals generally receive significantly larger budgets, per patient, than lower-level (district) hospitals. One reason for these differential allocations is the widely held belief that national hospitals treat persons with more difficult illnesses and persons who are more severely ill than do other, non-national, hospitals. This belief is but a presumption and one that warrants investigation. This paper analyzes expenditures among public hospitals in El Salvador over a 12-year period to address this question. While controlling for patient morbidity, outputs and other characteristics, district hospitals are found to be substantially underfunded relative to national hospitals. Four policy options to redress this situation are examined.
Assuntos
Alocação de Recursos para a Atenção à Saúde , Hospitais Públicos/economia , Risco Ajustado , Orçamentos , El Salvador , Hospitais de Distrito/economia , Humanos , Análise de RegressãoRESUMO
Vitamin A deficiency (VAD) is a serious and widespread public health problem in the Philippines. Initiated in 1993, the Philippines National Vitamin A Supplementation Program (NVASP) is one of the oldest, most mature and comprehensive of its kind. This paper presents a cost-effectiveness and efficiency analysis of the NVASP and of a hypothetical program of vitamin A fortification of wheat flour that was conducted to inform policymakers as to how to modify the program. Employing a proxy effectiveness indicator of VAD--the intake of < 70% of the recommended daily allowance of vitamin A--in a series of simulations using individual child consumption data, the analysis finds that fortification is more efficient in reducing inadequate vitamin A intake (IVAI) compared to the NVASP. Due to the nature of food consumption patterns, however, fortification alone, is not enough. At what is regarded as the maximum politically acceptable fortification level, there will still be 2.2 million (29%) Filipino children aged 12-59 months who will have IVAI. An investigation of the cost and efficiency of geographically targeted supplementation programs reveals that maintaining a universal supplementation program in urban areas and, in rural areas, introducing a targeted program to only the poorest municipalities (where the prevalence of VAD is the highest) will provide a more acceptable public health policy response than fortification alone. Such a policy will reduce incremental direct Government expenditures on vitamin A programs by nearly 20% and will reduce the number of children with IVAI to 900,000 (12%) Filipino children. The paper describes the fortification and supplementation programs, and how their costs were estimated. Lessons for program designers and policymakers in other countries in which vitamin A deficiency constitutes a public health problem are also discussed.
Assuntos
Custos de Cuidados de Saúde , Planejamento em Saúde , Programas Nacionais de Saúde/economia , Deficiência de Vitamina A/prevenção & controle , Pré-Escolar , Análise Custo-Benefício , Suplementos Nutricionais/economia , Farinha , Alimentos Fortificados/economia , Gastos em Saúde , Humanos , Lactente , Marketing de Serviços de Saúde/economia , Modelos Econométricos , Programas Nacionais de Saúde/organização & administração , Filipinas/epidemiologia , Deficiência de Vitamina A/epidemiologiaRESUMO
Until the mid-1960s, the market-based, dependent-development-conditioned structure of Latin American health systems reflected the skewed distribution of wealth in the region: most (including government) health resources were found in curative care medicine and were concentrated in the capital cities, where they primarily served the needs of the elite. But for many countries of the area, the 1964 PAHO-led efforts to introduce health planning, intended as a first step in rationalizing the health sector, marked a fundamental turning point in the structural development of their delivery systems. Since then, this commitment has been reaffirmed in the Latin American Ministers of Health's 1973 adoption of the primary care approach as the cornerstone of their national health plans, and their ongoing endorsement and pursuit of "Health For All by 2000." Guatemala, however, was and remains an exception. Guatemalan technocrats have proven unable to plan effectively. But, far more fundamentally, the Guatemalan oligarchy has proven unwilling to appropriate the resources necessary to effect change. The reforms that have been made have been the products of bilateral and multilateral agencies, which have conceptualized, promoted, designed, built, and underwritten them. Those changes have not altered the fundamental structure of the system, but instead have been tacked onto it, and exemplify what may be termed "additive reform." Evidence suggests that without the continued sponsorship, support, and guidance of the bilateral and multilateral agencies, even these "reforms" will prove evanescent.
PIP: Until the mid 1960s, Latin American health system reflected the skewed distribution of wealth in the region: most health resources were found in curative care medicine and were concentrated in the capital cities, where they primarily served the needs of the elite. For many countries, however, the 1964 Pan American Health Organization's (PAHO) efforts to introduce health planning, intended as a 1st step in rationalizing the health sector, marked a fundamental turning point in the structural development of their delivery systems. Guatemala, however, was and remains an exception. Its technocrats have proven unable to plan effectively; no single entity is responsible for health sector planning, and the 5-year plans have come to consist of disjointed mini-plans, each reflecting the aims, desires and goals of a particular vested interest group or institution. The Guatemalan oligarchy has proven unwilling to appropriate the resources necessary to effect change. The reforms that have been made have been the products of bilateral and multilateral agencies such as the InterAmerican Development Bank, USAID, UNICEF, Kreditanstaldt and PAHO, which have conceptualized, promoted, designed, built and underwritten them. Those changes have not altered the fundamental structure of the system, but instead have been tacked onto it, and exemplify what may be termed additive reform. The government of Guatemala's own commitment to these outside agency funded projects is reflected in the recurrent shortfall of current or operating funds, and in the rapid depreciation of facilities. Evidence suggests that without the continued sponsorship, support, and guidance of the bilateral and multilateral agencies, even these additive reforms will not last.
Assuntos
Atenção à Saúde/organização & administração , Política de Saúde/tendências , Guatemala , Planejamento em Saúde/história , História do Século XX , Cooperação Internacional , América Latina , Organização Pan-Americana da Saúde , Atenção Primária à Saúde , Classe Social , Fatores SocioeconômicosRESUMO
Normal hypothalamic-pituitary-adrenal (HPA) axis activity leading to the rhythmic and episodic release of adrenal glucocorticoids (GCs) is essential for body homeostasis and survival during stress. Acting through specific intracellular receptors in the brain and periphery, GCs regulate behaviour, as well as metabolic, cardiovascular, immune and neuroendocrine activities. By contrast to chronic elevated levels, circadian and acute stress-induced increases in GCs are necessary for hippocampal neuronal survival and memory acquisition and consolidation, as a result of the inhibition of apoptosis, the facilitation of glutamatergic neurotransmission and the formation of excitatory synapses, and the induction of immediate early genes and dendritic spine formation. In addition to metabolic actions leading to increased energy availability, GCs have profound effects on feeding behaviour, mainly via the modulation of orexigenic and anorixegenic neuropeptides. Evidence is also emerging that, in addition to the recognised immune suppressive actions of GCs by counteracting adrenergic pro-inflammatory actions, circadian elevations have priming effects in the immune system, potentiating acute defensive responses. In addition, negative-feedback by GCs involves multiple mechanisms leading to limited HPA axis activation and prevention of the deleterious effects of excessive GC production. Adequate GC secretion to meet body demands is tightly regulated by a complex neural circuitry controlling hypothalamic corticotrophin-releasing hormone (CRH) and vasopressin secretion, which are the main regulators of pituitary adrenocorticotrophic hormone (ACTH). Rapid feedback mechanisms, likely involving nongenomic actions of GCs, mediate the immediate inhibition of hypothalamic CRH and ACTH secretion, whereas intermediate and delayed mechanisms mediated by genomic actions involve the modulation of limbic circuitry and peripheral metabolic messengers. Consistent with their key adaptive roles, HPA axis components are evolutionarily conserved, being present in the earliest vertebrates. An understanding of these basic mechanisms may lead to novel approaches for the development of diagnostic and therapeutic tools for disorders related to stress and alterations of GC secretion.
Assuntos
Glucocorticoides/fisiologia , Sistema Hipotálamo-Hipofisário/fisiologia , Sistemas Neurossecretores/fisiologia , Sistema Hipófise-Suprarrenal/fisiologia , Estresse Fisiológico/fisiologia , Animais , Encéfalo/fisiologia , Ingestão de Alimentos/fisiologia , Retroalimentação Fisiológica/fisiologia , Mediadores da Inflamação/fisiologia , Modelos Biológicos , Plasticidade Neuronal/fisiologia , Receptores de Glucocorticoides/fisiologia , Receptores de Mineralocorticoides/fisiologiaRESUMO
Depressive disorder involves emotional, cognitive, autonomic and endocrine alterations and also evidences support the role of stress in the development of this disorder. Because the hypothalamic-pituitary-adrenal axis is involved in the stress response with a concomitant rise in plasma corticoids, the present study compares the antidepressant effects of sertraline (10mg/kg, i.p.) on behavioral changes elicited by (i) restraint stress (2.5h/day for 13days) and (ii) corticosterone injections (30mg/kg, s.c., for 13days). Stressed animals, but not corticosterone-treated animals displayed anxiety behavior and a reduction in the acquisition of a conditioned avoidance response to 25% of control levels (8.0±2.2 vs. 31.7±3.2), being this effect partly sensitive to sertraline. Stressed, but not corticosterone-treated, animals displayed an increased escape failure compared with the control group (24.6%±3.5 vs. 1.6±0.7), an effect partly prevented by sertraline treatment (7.3%±2.0). Both stressed rats and corticosterone-treated rats showed an increase in immobility in the forced swim test, an effect prevented by sertraline. These results suggest that the altered behaviors elicited by stress and corticosterone can be explained by neural modifications that are sensitive to the sertraline antidepressant.
Assuntos
Antidepressivos de Segunda Geração/uso terapêutico , Corticosterona/farmacologia , Depressão/psicologia , Sertralina/uso terapêutico , Estresse Psicológico/psicologia , Glândulas Suprarrenais/efeitos dos fármacos , Animais , Ansiedade/psicologia , Aprendizagem da Esquiva/efeitos dos fármacos , Condicionamento Operante/efeitos dos fármacos , Corticosterona/sangue , Depressão/etiologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Restrição Física , Estresse Psicológico/complicações , Natação/psicologia , Aumento de Peso/efeitos dos fármacosAssuntos
Dietoterapia , Assistência Domiciliar , Fenilcetonúrias/terapia , Criança , Pré-Escolar , Culinária , Proteínas Alimentares , Dietética , Feminino , Educação em Saúde , Humanos , Lactente , Masculino , Relações Mãe-Filho , Planejamento de Assistência ao Paciente , Satisfação Pessoal , FenilalaninaRESUMO
A link between stressful life events and development or exacerbation of depression has been established via a large body of evidence. An alteration in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis in depression has also been associated with an increase in cortisol secretion. As arginine-vasopressin (AVP) plays an important role in the activation of HPA axis during stress, the present study investigated ACTH and cortisol secretory response induced by an AVP-related peptide desmopressin (ddAVP) in patients with major depression. Prior to antidepressant treatment, endocrinological parameters were evaluated and correlated with the clinical response to venlafaxine treatment, which offers a dual antidepressant action. Depressive patients with no other psychiatric pathology were evaluated with 17-item Hamilton Depression Scale (HAM-D) in order to follow-up the response to venlafaxine. After 1 wk of treatment, 60% of patients reduced their initial HAM-D score to at least 25%; this group was classified as early responders. The other group (40%) started to reduce significantly their HAM-D score after 3 wk of treatment and was classified as late responders. After 6 wk of treatment both groups have reduced HAM-D score to at least 25% of the baseline score. Prior to the pharmacological treatment, both early and late responders showed salivary cortisol rhythm and urinary free cortisol (UFC) in 24-h similar to healthy subjects. However, we did observe differences in basal ACTH secretion, showing that the late responder group had higher basal ACTH than both early responders and controls. The ddAVP challenge promoted a robust secretion of ACTH only in late responders, suggesting a different sensitivity of pituitary vasopressin receptor. The differences in clinical response to venlafaxine among depressive patients seem to be related to endocrinological parameters.
Assuntos
Hormônio Adrenocorticotrópico/metabolismo , Antidepressivos de Segunda Geração/uso terapêutico , Cicloexanóis/uso terapêutico , Transtorno Depressivo/tratamento farmacológico , Hidrocortisona/metabolismo , Adulto , Ritmo Circadiano/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Resultado do Tratamento , Cloridrato de VenlafaxinaRESUMO
This article presents a case study of a US Agency for International Development-sponsored privatization effort in Bolivia. This privatization effort differs from AID's more common approach in that rather than merely helping already existing organizations to expand, this project has created a new organization. More ambitious and encompassing, this approach is also preferable because it directly addresses one of the most serious bottlenecks to economic development, viz., organizational development. The article describes the evolution of PROSALUD, a private, non-profit network of 17 community-sponsored health centers. The article describes factors and characteristics which have either conditioned or have directly contributed to PROSALUD's success. First, PROSALUD's health care environment is analysed, starting with a broad brush profile of select characteristics and trends which exist throughout the health sector of Bolivia, then narrows the focus to the local health sector. The structure and operations of PROSALUD are then analysed, focusing on the organization's managerial practices and financing and the series of tradeoffs it has been forced to strike: in its pricing strategy, between striving for financial viability and maintaining access to care; between, on the one hand, responding to community needs and demands and improving coverage by opening more facilities, and, on the other hand, focusing managerial efforts and outreach on a more limited number of clinics and neighborhoods; between providing a socially desirable mix of services--in particular, continuing to provide a great deal of free preventive care--and focusing care on more lucrative curative services; between maintaining commitments to neighborhoods and communities and eliminating the less economically viable (especially rural) clinics.
PIP: This article presents a case study of a USAID sponsored privatization effort in Bolivia. This privatization effort differs from AID's more common approach in that rather than simply helping already existing organizations to expand, this project has created a new organization. More ambitious and encompassing, this approach is also preferable because it directly addresses 1 of the most serious bottlenecks to economic development, i.e. organizational development. The article described the evolution of PROSALUD, a private, nonprofit network of 17 community-sponsored health centers. Also discussed are factors and characteristics which have either conditioned or directly contributed to the success of the organization. 1st, PROSALUD's healthcare environment is analyzed, beginning with a broad brush profile of select characteristics and trends which exist throughout the health sector of Bolivia, then narrows the focus to the local health sector. The structure and operations of PROSALUD are then analyzes, focusing on the organizations managerial practices and financing and the series of tradeoffs it has been forced to strike. In its pricing strategy, there has been striving for financial viability and maintaining access to care; between on the 1 hand, responding to community needs and demands and improving coverage by opening more facilities, and, on the other hand, focusing managerial efforts and outreach on a more limited number of clinics and neighborhoods. There has also been an attempt to provide a socially desirable mix of services, in particular, continuing to provide a great deal of free preventive care and focusing care on more lucrative curative services, between maintaining commitments to neighborhood and communities, and eliminating the less economically viable (especially rural) clinics.
Assuntos
Centros Comunitários de Saúde/organização & administração , Atenção Primária à Saúde/organização & administração , Privatização , Bolívia , Organização do Financiamento/organização & administração , Saúde Global , Órgãos Governamentais , HumanosRESUMO
Most Latin American social security institutes are direct providers of medical care services to their beneficiaries. As many of the institutes have developed serious financial problems over the course of the last decade and a half, they have come under increasing attack for (a) exacerbating inequalities in access to and use of health care, (b) further heightening the geographic overconcentration of services, (c) focusing a disproportionate amount of resources on high technology, curative care to the near total exclusion of primary health care, and (d) being administratively top heavy and, more generally, inefficient. In the past few years, many Latin American countries have begun searching for methods to ameliorate these problems. This paper analyzes three recent efforts, all of which involve some degree of privatization: (1) El Salvador's partial privatization of specialty physician outpatient consultations, (2) Peru's minor surgery and its decentralized ambulatory care programme, and (3) Nicaragua's "administrative services only' approach wherein social security beneficiaries choose to join a certified public or private provider organization for one year, and, on behalf of the individual, social security pays the organization a fixed, annual, per capita fee to provide all health care for the enrollee. The paper also identifies political and technical considerations, as well as health care market characteristics that have shaped these efforts and that condition their likelihood of success, including: the size, composition, level of capacity utilization, degree of organization and geographic distribution of private sector resources; relative prices in the private vis-a-vis the public sector; and the size and nature of the private health insurance market. Other Latin American countries would do well to examine these factors and characteristics before embarking on efforts to reform their own social security health care delivery systems.
Assuntos
Atenção à Saúde/organização & administração , Privatização , Previdência Social/organização & administração , Assistência Ambulatorial/economia , Assistência Ambulatorial/organização & administração , Comportamento do Consumidor , Atenção à Saúde/economia , Atenção à Saúde/normas , El Salvador , Reforma dos Serviços de Saúde/organização & administração , Acessibilidade aos Serviços de Saúde , Modelos Organizacionais , Nicarágua , Peru , Qualidade da Assistência à SaúdeRESUMO
More than 250 million of the world's children suffer from vitamin A deficiency. Nepal is one of 60 countries in which this deficiency constitutes a significant public health problem. Each year in Nepal, vitamin A deficiency is responsible for the deaths of 9000 children and for 2500 children becoming permanently blind. The Nepal National Vitamin A Program (NVAP) was begun in 1993 in eight of the country's 75 districts. By the end of 1997, the programme covered 32 districts, and by 2003 its coverage will be nationwide. The Nepal NVAP is considered by many to be a highly successful, model programme. It consists primarily of distributing high-dose vitamin A capsules to all children 6 to 60 months of age during twice-yearly campaigns. The capsule distribution is carried out by a previously existing network of Female Community Health Volunteers (FCHVs) that has been reinvigorated by the highly visible and universally acclaimed success of the NVAP. An important strategy of the programme has been the empowerment of the FCHVs, which has been accomplished by organizing, training and motivating community workers and other representatives from education, agriculture and other sectors, as well as political representatives, to support the FCHVs. The annual cost of the NVAP is US$1.7 million. It costs $1.25 to deliver two vitamin A capsules to each participant. The cost per averted death is $327. The NVAP reduces the incidence and severity of diarrhoeal disease and measles, which in turn reduces the need for Ministry of Health services, thereby annually saving the Government of Nepal $1.5 million. Factoring in these cost savings, the net annual cost of the current NVAP is $167,000, and the net annual cost of the permanent, nationwide programme is estimated at $1.1 million. The NVAP is a highly cost-effective programme. The article concludes with a discussion of the sustainability and replicability of the programme.