RESUMO
Improving the food supply chain efficiency has been identified as an essential means to enhance food security, while reducing pressure on natural resources. Adequate food loss and waste (FLW) management has been proposed as an approach to meet these objectives. The main hypothesis of this study is to consider that the "strong fluctuations and short-term changes" on eating habits may have major consequences on potential FLW generation and management, as well as on GHG emissions, all taking into account the nutritional and the economic cost. Due to the exceptional lockdown measures imposed by the Spanish government, as a consequence of the emerging coronavirus disease, COVID-19, food production and consumption systems have undergone significant changes, which must be properly studied in order to propose strategies from the lessons learned. Taking Spain as a case study, the methodological approach included a deep analysis of the inputs and outputs of the Spanish food basket, the supply chain by means of a Material Flow Analysis, as well as an economic and comprehensive nutritional assessment, all under a life cycle thinking approach. The results reveal that during the first weeks of the COVID-19 lockdown, there was no significant adjustment in overall FLW generation, but a partial reallocation from extra-domestic consumption to households occurred (12% increase in household FLW). Moreover, the economic impact (+11%), GHG emissions (+10%), and the nutritional content (-8%) complete the multivariable impact profile that the COVID-19 outbreak had on FLW generation and management. Accordingly, this study once again highlights that measures aimed at reducing FLW, particularly in the household sector, are critical to make better use of food surpluses and FLW prevention and control, allowing us to confront future unforeseen scenarios.
Assuntos
Infecções por Coronavirus , Pandemias , Pneumonia Viral , Eliminação de Resíduos , Gerenciamento de Resíduos , Betacoronavirus , COVID-19 , Surtos de Doenças , Alimentos , Humanos , SARS-CoV-2 , EspanhaRESUMO
PURPOSE: The main purpose of this systematic review was to investigate the effect of compression treatment on the perioperative course of ankle fractures and describe its effect on edema, pain, ankle joint mobility, wound healing complication, length of stay (LOS) and time to surgery (TTS). The aim was to suggest a recommendation to clinicians considering implementing compression therapy in the standard care of the ankle fracture patient, based on the existing literature. METHODS: We conducted a systematic search of literature including studies concerning adult patients with unstable ankle fractures undergoing surgery, testing either intermittent pneumatic compression, compression bandage and/or compression stocking and reporting its effect on edema, pain, ankle joint mobility, wound healing complication, LOS and TTS. To conclude on data a narrative synthesis was performed. RESULTS: The review included eight studies (451 patients). Seven studies found a significant effect on edema, two studies described a significant reduction in pain, one a positive effect on ankle movement, two a positive effect on wound healing, one a reduction in LOS and finally two studies reported reduction in TTS. A systematic bias assessment showed that the included studies had methodological limitations influencing the confidence in the effect estimate. CONCLUSIONS: Compression therapy has a beneficial effect on edema reduction and probably a positive effect on pain and ankle joint mobility, but with the methodological limitations in the included studies it is not possible to make a solid conclusion on the effect on wound healing, LOS and TTS.
Assuntos
Fraturas do Tornozelo/cirurgia , Bandagens Compressivas , Edema/prevenção & controle , Dispositivos de Compressão Pneumática Intermitente , Complicações Pós-Operatórias/prevenção & controle , Humanos , Tempo de Internação , Medição da Dor , CicatrizaçãoRESUMO
Neurons producing melanin-concentrating hormone (MCH) are located in the tuberal lateral hypothalamus (LHA) and in the rostromedial part of the zona incerta (ZI). This distribution suggests that rostromedial ZI shares some common features with the LHA. However, its functions with regard to arousal or feeding, which are often associated with the LHA, have not been thoroughly investigated. This study analyses the responses in the tuberal LHA and adjacent rostromedial ZI after experiments related to arousal, exploration, food teasing and ingestive behavior. Specific aspects of the connections of the rostromedial ZI were also studied using retrograde and anterograde tract-tracing approaches. The rostromedial ZI is activated during exploratory and teasing experiments. It receives specific projections from the frontal eye field and the anterior pole of the superior colliculus that are involved in gaze fixation and saccadic eye movements. It also receives projections from the laterodorsal tegmental nucleus involved in attention/arousal. By contrast, the tuberal LHA is activated during wakefulness and exploratory behavior and reportedly receives projections from the medial prefrontal and insular cortex, and from several brainstem structures such as the periaqueductal gray. We conclude that the rostromedial ZI is involved in attentional processes while the adjacent tuberal LHA is involved in arousal.
Assuntos
Nível de Alerta , Atenção , Comportamento Animal , Região Hipotalâmica Lateral/metabolismo , Neurônios/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Zona Incerta/metabolismo , Animais , Ingestão de Alimentos , Comportamento Exploratório , Comportamento Alimentar , Região Hipotalâmica Lateral/citologia , Masculino , Vias Neurais/metabolismo , Ratos Sprague-Dawley , Movimentos Sacádicos , Zona Incerta/citologiaRESUMO
The neurons of the lateral hypothalamus that contain hypocretin/orexin (hcrt/orx) are thought to promote arousal through the excitatory action they exert on the multiple areas to which they project within the CNS. We show here that the hcrt/orx peptides can also exert a strong action on the amygdala, a structure known for its implication in emotional aspects of behavior. Indeed, the hcrt/orx peptides, applied in acute rat brain slices, excite a specific class of "low threshold burst" neurons in the central medial (CeM) nucleus which is considered as a major output of the amygdala. These excitatory effects are postsynaptic, mediated by Hcrt2/OX2 receptors and result from the closure of a potassium conductance. They occur on a class of neurons that are also excited by vasopressin acting through V1a receptors. These results suggest that the hcrt/orx system can act through the amygdala to augment arousal and evoke the autonomic and behavioral responses associated with fear, stress or emotion.
Assuntos
Tonsila do Cerebelo/metabolismo , Potenciais Pós-Sinápticos Excitadores/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Vias Neurais/metabolismo , Neurônios/metabolismo , Neuropeptídeos/metabolismo , Transmissão Sináptica/fisiologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Tonsila do Cerebelo/efeitos dos fármacos , Animais , Nível de Alerta/efeitos dos fármacos , Nível de Alerta/fisiologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Medo/efeitos dos fármacos , Medo/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/farmacologia , Vias Neurais/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neuropeptídeos/farmacologia , Receptores de Orexina , Orexinas , Técnicas de Cultura de Órgãos , Canais de Potássio/efeitos dos fármacos , Canais de Potássio/metabolismo , Ratos , Receptores Acoplados a Proteínas G/efeitos dos fármacos , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Neuropeptídeos/efeitos dos fármacos , Receptores de Neuropeptídeos/metabolismo , Receptores de Vasopressinas/agonistas , Receptores de Vasopressinas/metabolismo , Estresse Psicológico/metabolismo , Estresse Psicológico/fisiopatologia , Transmissão Sináptica/efeitos dos fármacos , Vasopressinas/metabolismo , Vasopressinas/farmacologiaRESUMO
OBJECTIVE: Tumour features were evaluated during intermittent androgen suppression (IAS), and their prognostic impact on the first off-treatment time was analysed. PATIENTS AND METHODS: Twenty patients with advanced prostate cancer underwent three consecutive prostate biopsies during the first cycle, namely at the beginning of androgen deprivation, 8 months after continuous therapy and at the time of prostate-specific antigen (PSA) progression above 20 ng/ml. Biopsy specimens were immunohistochemically processed and analysed for the apoptotic index (AI), Ki-67, p53 and Bcl-2 to investigate eventual changes over time. Correlations and regression analysis were performed to assess the prognostic significance of clinical and pathological parameters in predicting the first off-treatment time. RESULTS: In contrast to the AI, p53 and Bcl-2, Ki-67 was the only marker that significantly changed over time (P=0.008). The first off-treatment time correlated significantly with pretreatment PSA (r=-0.594; P<0.01), testosterone recovery time (r=0.590; P=0.013) and biopsy grade (r=-0.738; P<0.01); only the latter gaining an independent factor in the multivariate analysis (P=0.022). CONCLUSIONS: During IAS, Ki-67 was the only molecular marker that consistently changed over time. However, it did not correlate with off-treatment time that was predicted independently by the initial biopsy grade only. First off-treatment time was best predicted by clinical parameters and molecular markers from needle biopsies did not further contribute to a better patient selection.
Assuntos
Antagonistas de Androgênios/uso terapêutico , Biomarcadores Tumorais/análise , Carcinoma/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anilidas/administração & dosagem , Anilidas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Biópsia , Carcinoma/diagnóstico , Carcinoma/patologia , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Gosserrelina/administração & dosagem , Gosserrelina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nitrilas , Prognóstico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Testosterona/sangue , Compostos de Tosil , Suspensão de TratamentoRESUMO
Sensitivity to the attentional effects of SKF81297, a selective full agonist at dopamine D(1) receptors, was assessed in adult rats exposed to cocaine prenatally (via intravenous injections) and controls. The task assessed the ability of the subjects to monitor an unpredictable light cue of either 300 or 700 msec duration and to maintain performance when presented with olfactory distractors. SKF81297 decreased nose pokes before cue presentation and increased latencies and response biases (the tendency to respond to the same port used on the previous trial), suggesting an effect of SKF81297 on the dopamine (DA) systems responsible for response initiation and selection. The cocaine-exposed (COC) and control animals did not differ in sensitivity to the effects of SKF81297 on these measures. In contrast, the COC animals were significantly more sensitive than were controls to the impairing effect of SKF81297 on omission errors, a measure of sustained attention. This pattern of results provides evidence that prenatal cocaine exposure produces lasting changes in the DA system(s) subserving sustained attention but does not alter the DA system(s) underlying response selection and initiation. These findings also provide support for the role of D(1) receptor activation in attentional functioning.
Assuntos
Atenção/efeitos dos fármacos , Benzazepinas/farmacologia , Cocaína/administração & dosagem , Efeitos Tardios da Exposição Pré-Natal , Receptores de Dopamina D1/agonistas , Animais , Atenção/fisiologia , Comportamento Animal/efeitos dos fármacos , Sinais (Psicologia) , Aprendizagem por Discriminação/efeitos dos fármacos , Agonistas de Dopamina/farmacologia , Relação Dose-Resposta a Droga , Feminino , Injeções Intravenosas , Masculino , Estimulação Luminosa , Gravidez , Ratos , Ratos Long-Evans , Tempo de Reação/efeitos dos fármacos , Olfato/efeitos dos fármacosRESUMO
PURPOSE: To evaluate a strategy that avoids radiotherapy in children less than 6 years of age with newly diagnosed malignant brain tumors, by administering myeloablative consolidation chemotherapy with autologous bone marrow reconstitution (ABMR) after maximal surgical resection and conventional induction chemotherapy. PATIENTS AND METHODS: Between March 1991 and April 1995, 62 children (median age, 30 months) with newly diagnosed malignant brain tumors were enrolled onto this trial. Children received conventional induction chemotherapy with vincristine, cisplatin, cyclophosphamide, and etoposide, repeated every 3 weeks for five cycles. Children without disease progression on induction chemotherapy were offered consolidation with myeloablative chemotherapy that incorporated carboplatin, thiotepa, and etoposide followed by ABMR. Irradiation was used only for residual tumor at consolidation or for progressive/recurrent disease. RESULTS: Induction chemotherapy was well tolerated by most patients; however, progression was noted in 17 children (27%) and four (6%) died of treatment complications. Of 37 children who received consolidation chemotherapy with ABMR, 15 are free of disease progression (median post-ABMR without further treatment, >44 months). The remaining 22 all progressed within 15 months of ABMR; three of 37 (8%) died of treatment-related complications. The 3-year overall survival (OS) and event-free survival (EFS) rates from diagnosis for all children are 40% (95% confidence interval [CI], 28% to 52%) and 25% (95% CI, 13% to 37%), respectively. Radiotherapy was administered to 19 of 62 children: 17 for progressive disease (PD) and two for residual disease at the time of ABMR. CONCLUSION: A significant proportion of children with malignant brain tumors can avoid radiotherapy and prolonged maintenance chemotherapy yet still achieve durable remission with this brief intensive chemotherapy regimen.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Pré-Escolar , Cisplatino/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Progressão da Doença , Etoposídeo/administração & dosagem , Feminino , Humanos , Lactente , Masculino , Recidiva Local de Neoplasia , Neutropenia/induzido quimicamente , Indução de Remissão , Trombocitopenia/induzido quimicamente , Transplante Autólogo , Vincristina/administração & dosagemRESUMO
As an investigational fibrinolytic agent for acute myocardial infarction, intravenous recombinant tissue-type plasminogen activator (rt-PA) has been administered primarily in tertiary care and university centers. To determine the value of early initiation of such therapy, two satellite community hospital emergency rooms were established for use of rt-PA and the experience was compared among 142 consecutive patients who were transferred to a regional center for acute cardiac catheterization after intravenous rt-PA therapy. In Group I (n = 19), patients received rt-PA after interhospital transport to the regional center, but before cardiac catheterization. In Group II (n = 70), rt-PA therapy was initiated by the helicopter physician and nurse team after their arrival at the local community hospital emergency room. Group III patients (n = 53) had rt-PA administered in the local community hospital by the emergency room physician. Group III patients had earlier initiation of therapy (2.1 +/- 0.8 hours in Group III versus 3.8 +/- 1.2 hours in combined Groups I and II, p less than 0.001) and an increased rate of infarct vessel recanalization on the 90 minute coronary angiogram (81 in Group III versus 67% in combined Groups I and II, p = 0.057). The patients in Group III had a higher acute left ventricular ejection fraction (54 +/- 8% versus 50 +/- 9.5% in combined Groups I and II, p less than 0.01) and a trend toward an increased 7 day ejection fraction (55.5 +/- 9% versus 51.7 +/- 9.5%, respectively, p = 0.08).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Hospitais Comunitários , Infarto do Miocárdio/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Cateterismo Cardíaco , Feminino , Seguimentos , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Proteínas Recombinantes , Volume Sistólico , Fatores de Tempo , Ativador de Plasminogênio Tecidual/administração & dosagemRESUMO
Hypocretin/orexin (Hcrt/Orx) and melanin concentrating hormone (MCH) are peptides contained in overlapping cell groups of the lateral hypothalamus and commonly involved in regulating sleep-wake states and energy balance, though likely in different ways. To see if these neurons are similarly or differentially modulated by neurotransmitters of the major brainstem arousal systems, the effects of noradrenaline (NA) and carbachol, a cholinergic agonist, were examined on identified Hcrt/Orx and MCH neurons in rat hypothalamic slices. Whereas both agonists depolarized and excited Hcrt/Orx neurons, they both hyperpolarized MCH neurons by direct postsynaptic actions. According to the activity profiles of the noradrenergic locus coeruleus and cholinergic pontomesencephalic neurons across the sleep-waking cycle, the Hcrt/Orx neurons would be excited by NA and acetylcholine (ACh) and thus active during arousal, whereas the MCH neurons would be inhibited by NA and ACh and thus inactive during arousal while disinhibited and possibly active during slow wave sleep. According to the present pharmacological results, Hcrt/Orx neurons may thus stimulate arousal in tandem with other arousal systems, whereas MCH neurons may function in opposition with other arousal systems and thus potentially dampen arousal to promote sleep.
Assuntos
Acetilcolina/fisiologia , Região Hipotalâmica Lateral/metabolismo , Hormônios Hipotalâmicos/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Melaninas/metabolismo , Neurônios/metabolismo , Neuropeptídeos/metabolismo , Norepinefrina/fisiologia , Hormônios Hipofisários/metabolismo , Acetilcolina/farmacologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Nível de Alerta/efeitos dos fármacos , Nível de Alerta/fisiologia , Agonistas Colinérgicos/farmacologia , Região Hipotalâmica Lateral/citologia , Região Hipotalâmica Lateral/efeitos dos fármacos , Locus Cerúleo/fisiologia , Modelos Neurológicos , Inibição Neural/efeitos dos fármacos , Inibição Neural/fisiologia , Vias Neurais/citologia , Vias Neurais/efeitos dos fármacos , Vias Neurais/metabolismo , Neurônios/efeitos dos fármacos , Norepinefrina/farmacologia , Orexinas , Técnicas de Cultura de Órgãos , Técnicas de Patch-Clamp , Núcleo Tegmental Pedunculopontino/fisiologia , Ratos , Ratos Sprague-Dawley , Sono/fisiologia , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/fisiologiaRESUMO
Salt sensitivity (changes in blood pressure in response to alterations in salt intake) may be a risk factor for hypertension. In the present study, we examined the prevalence of salt sensitivity based on two different classifications in healthy black male and female adolescents (aged 13 to 16 years). A total of 135 black adolescents participated in a 50 mmol/24 h low sodium diet for 5 days and a 150 mmol/24 h NaCl supplement for 10 days. Dietary compliance was defined as sodium excretion less than or equal to 50 mmol/24 h for the low sodium diet and greater than or equal to 165 mmol/24h for the high NaCl supplement. Salt sensitivity was defined by two classifications: (1) as a decrease in mean blood pressure greater than or equal to 5 mm Hg from baseline to the low sodium diet, and (2) as an increase in mean blood pressure greater than or equal to 5 mm Hg from the low sodium diet to the high NaCl supplement. With classification 1, 14% of boys were identified as salt sensitive compared with 22% of girls. With classification 2, however, 31% of boys were identified as salt sensitive compared with 18% of girls. Analyses based on changes in systolic pressure demonstrated similar findings across sex, although overall classifications based on systolic pressure yielded a greater percentage of salt-sensitive subjects. These sex differences in classification patterns were not due to differences in other important variables, such as changes in sodium excretion, potassium excretion, or Quetelet index. These results suggest that the prevalence of salt sensitivity differs by sex depending on the type of protocol used for the classification of salt sensitivity in a black pediatric population.
Assuntos
População Negra , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/classificação , Cloreto de Sódio na Dieta/farmacologia , Adolescente , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Humanos , Hipertensão/induzido quimicamente , Masculino , Prevalência , Fatores SexuaisRESUMO
The polymorphisms of the estrogen receptor (ER) gene defined by the restriction enodonucleases PvuII and XbaI have recently been reported to be associated with bone mineral density (BMD) in postmenopausal women. To investigate the possible relation of the PvuII and XbaI restriction fragment-length polymorphisms of the ER gene with BMD in Danish postmenopausal women, two studies were undertaken: 1) a cross-sectional study of 499 postmenopausal women, where the ER genotypes and alleles were related to BMD of the hip, spine, and lower forearm; and 2) a longitudinal study of 101 postmenopausal women followed up for 18 years. In the latter study, late postmenopausal bone loss in the hip and spine was determined over a period of 6 years in women (mean age of 63 to 69 years), and long-term postmenopausal bone loss in the lower forearm was determined over a period of 18 years in women (mean age of 51 to 69 years). Genotyping was performed through the restriction cleavage of polymerase chain reaction-amplified genomic DNA with the two restriction enzymes, PvuII and XbaI. Restriction fragment-length polymorphisms were represented as P or p (PvuII) and X or x (XbaI), with the lower case letters signifying the presence of the restriction site. The frequencies of the ER genotypes were similar to previously published genotype frequencies in Caucasian and Asian populations. No significant effect of the ER genotypes or alleles on BMD was found at any site, nor was there a relation between ER genotypes and the rate of bone loss either in the hip and spine over 6 years, or in the lower forearm over 18 years. In conclusion, we could not demonstrate any major effect of the ER gene polymorphisms on BMD or rate of bone loss in healthy postmenopausal Danish women.
Assuntos
Densidade Óssea/genética , Densidade Óssea/fisiologia , Osteoporose Pós-Menopausa/genética , Osteoporose Pós-Menopausa/metabolismo , Polimorfismo de Fragmento de Restrição , Receptores de Estrogênio/genética , Idoso , Alelos , Sequência de Bases , Estudos Transversais , Primers do DNA/genética , Dinamarca , Terapia de Reposição de Estrogênios , Feminino , Genótipo , Humanos , Estudos Longitudinais , Pessoa de Meia-IdadeRESUMO
Innervation of diencephalic neurons producing melanin-concentrating hormone by choline acetyltransferase-containing axons was examined using double immunohistochemistry. In the rostromedial zona incerta and perifornical regions of the lateral hypothalamic area, many choline acetyltransferase-positive fibers were detected in the immediate vicinity of melanin-concentrating hormone perikarya and their proximal dendrites. Putative contact sites were less abundant in the far lateral hypothalamus, and only scattered close to the third ventricle. After injections of the retrograde tracer FluoroGold, most of these projections appeared to originate in the pedunculopontine and laterodorsal tegmental nuclei. Finally, to determine the putative effect of acetylcholine on the melanin-concentrating hormone neuron population, the cholinergic agonist carbachol was added to the medium of hypothalamic slices in culture. Using competitive reverse transcriptase-polymerase chain reaction, carbachol was found to induce a rapid increase in the melanin-concentrating hormone messenger RNA expression. This response was abolished by both atropine, a muscarinic antagonist, and hexamethonium, a nicotinic antagonist. Thus, the bulk of these results indicates that the diencephalic melanin-concentrating hormone neurons are targeted by activating ascending cholinergic projections.
Assuntos
Fibras Colinérgicas/fisiologia , Diencéfalo/metabolismo , Hormônios Hipotalâmicos/biossíntese , Melaninas/biossíntese , Neurônios/metabolismo , Hormônios Hipofisários/biossíntese , Transmissão Sináptica/fisiologia , Vias Aferentes/fisiologia , Animais , Colina O-Acetiltransferase/metabolismo , Colinérgicos/farmacologia , Diencéfalo/citologia , Diencéfalo/efeitos dos fármacos , Diencéfalo/enzimologia , Hormônios Hipotalâmicos/genética , Imuno-Histoquímica , Masculino , Melaninas/genética , Neurônios/enzimologia , Hormônios Hipofisários/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Distribuição Tecidual/fisiologiaRESUMO
The orexins (orexin A and B, also known as hypocretin 1 and 2) are two recently identified neuropeptides (de Lecea et al., 1998; Sakurai et al., 1998) which are importantly implicated in the control of wakefulness (for reviews see Hungs and Mignot, 2001; van den Pol, 2000; Willie et al., 2001 ). Indeed, alteration in these peptides' precursor, their receptors or the hypothalamic neurones that produce them leads to the sleep disorder narcolepsy (Chemelli et al., 1999; Lin et al., 1999; Peyron et al., 2000; Thannickal et al., 2000). The mechanisms by which the orexins modulate wakefulness, however, are still unclear. Their presence in fibres coursing from the hypothalamus (Peyron et al., 1998) up to the preoptic area (POA) and basal forebrain (BF) suggests that they might influence the important sleep and waking neural systems situated there (Jones, 2000). The present study, performed in rat brain slices, demonstrates, however, that the orexins have no effect on the GABA sleep-promoting neurones of the POA, whereas they have a strong and direct excitatory effect on the cholinergic neurones of the contiguous BF. In addition, by comparing the effects of orexin A and B we demonstrate here that orexins' action depends upon orexin type 2 receptors (OX(2)), which are those lacking in narcoleptic dogs (Lin et al., 1999). These results suggest that the orexins excite cholinergic neurones that release acetylcholine in the cerebral cortex and thereby contribute to the cortical activation associated with wakefulness.
Assuntos
Acetilcolina/metabolismo , Núcleo Basal de Meynert/metabolismo , Biotina/análogos & derivados , Proteínas de Transporte/metabolismo , Fibras Colinérgicas/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular , Neurônios/metabolismo , Neuropeptídeos/metabolismo , Vigília/fisiologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Núcleo Basal de Meynert/citologia , Núcleo Basal de Meynert/efeitos dos fármacos , Proteínas de Transporte/farmacologia , Fibras Colinérgicas/efeitos dos fármacos , Fibras Colinérgicas/ultraestrutura , Relação Dose-Resposta a Droga , Inibição Neural/efeitos dos fármacos , Inibição Neural/fisiologia , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neuropeptídeos/farmacologia , Receptores de Orexina , Orexinas , Técnicas de Cultura de Órgãos , Área Pré-Óptica/citologia , Área Pré-Óptica/efeitos dos fármacos , Área Pré-Óptica/metabolismo , Ratos , Receptores Acoplados a Proteínas G , Receptores de Neuropeptídeos/efeitos dos fármacos , Receptores de Neuropeptídeos/metabolismo , Vigília/efeitos dos fármacos , Ácido gama-Aminobutírico/metabolismoRESUMO
The clinical significance of ventricular ectopic beats in the posthospital phase of myocardial infarction was studied in 272 patients aged 65 years or less who were followed up for 1 year after the infarction. Ventricular ectopic beats, identified in 6 hour electrocardiographic tape recordings, obtained before hospital discharge (study 1) and 5 months after discharge (study 2) increased in frequency and complexity in the 5 month interval. Ventricular ectopic beats at a rate of 20 or more per hour recorded before discharge were associated with complex ventricular ectopic patterns in the same 6 hour recording and with frequent (20 or more per hour), early cycle and bigeminal patterns in recordings mad 5 months later. Analysis with log-linear modeling indicated that the occurrence of complex ventricular ectopic beats at follow-up examination was associated with the concomitant use of antiarrhythmic agents,but not with use of digitalis, propranolol or tranquilizers. A ventricular ectopic beat frequency of 20 or more per hour at discharge was associated with increased (P less than 0.05) cardiac mortality in the initial 0 to 4 months after discharge but not in the subsequent 8 months; ectopic beats recorded in the 5 month follow-up study were not associated with increased cardiac mortality in the subsequent 5 to 12 months. The prognostic significance of ventricular ectopic beats is discussed in the light of these findings.
Assuntos
Complexos Cardíacos Prematuros/etiologia , Infarto do Miocárdio/complicações , Idoso , Eletrocardiografia , Seguimentos , Ventrículos do Coração , Humanos , Métodos , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/mortalidade , Prognóstico , Estudos Prospectivos , Gravação em Fita , Fatores de TempoRESUMO
The presence of the neurokinin B receptor (NK3 receptor) in the rat lateral hypothalamus and the zona incerta was previously reported. The aim of the present study was to define its cellular localization in these areas. Investigations, coupling immunocytochemical and in situ hybridization techniques, focussed on two neuron populations: the melanin-concentrating hormone (MCH) neurons and a population of neurons recognized by an ovine prolactin antiserum (PRL-ir neurons). While PRL-ir neurons did not exhibit NK3 immunoreactivity, 57% +/- 6% of MCH neurons were strongly stained by the NK3 antiserum. These results suggest that neurokinin B is involved in the regulation of MCH neuron activity via the NK3 receptor; they provide new bases for further investigations on MCH role in the control of food and water intake.
Assuntos
Química Encefálica/fisiologia , Hormônios Hipotalâmicos/metabolismo , Melaninas/metabolismo , Neurônios/metabolismo , Hormônios Hipofisários/metabolismo , Receptores da Neurocinina-3/metabolismo , Animais , Encéfalo/citologia , Imuno-Histoquímica , Hibridização In Situ , Masculino , Prolactina/fisiologia , Ratos , Ratos Sprague-DawleyRESUMO
Following an i.p. injection of 2-deoxyglucose (2DG), a nonmetabolizable analogue of glucose known to induce intracellular glucopenia, a progressive decrease in the level of hypocretin (Hcrt)/orexin mRNA was observed in the rat lateral hypothalamus while the melanin-concentrating hormone (MCH) expression in neighbouring neurons remained unaffected. This result together with the previously reported stimulation of Hcrt expression by insulin confirms that Hcrt neurons, but not MCH neurons, are sensitive to glucose availability and suggests that they respond through different mechanisms and/or different pathways to intracellular glucopenia and hypoglycemic conditions.
Assuntos
Proteínas de Transporte , Desoxiglucose/farmacologia , Expressão Gênica/efeitos dos fármacos , Região Hipotalâmica Lateral/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular , Neuropeptídeos , Neurotransmissores/genética , Animais , Glicemia/análise , Região Hipotalâmica Lateral/citologia , Hormônios Hipotalâmicos/genética , Hormônios Hipotalâmicos/metabolismo , Imuno-Histoquímica , Hibridização In Situ , Masculino , Melaninas/genética , Melaninas/metabolismo , Neurônios/metabolismo , Neurônios/fisiologia , Neurotransmissores/metabolismo , Orexinas , Hormônios Hipofisários/genética , Hormônios Hipofisários/metabolismo , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
The possibility of an effect of ethnicity on the pharmacokinetics of mycophenolic acid, the immunosuppressive metabolite of the prodrug mycophenolate mofetil, was studied over 90 days following renal transplantation in African American (n = 13) and Caucasian patients (n = 20). Since renal dysfunction and time after transplant surgery are two factors known to alter mycophenolic acid pharmacokinetics, two-way analysis of variance of the data at each time point with ethnicity and renal function status as covariates was used to evaluate the possibility of an ethnicity effect on the pharmacokinetic parameters. No statistically significant difference based on ethnicity was detected for the primary pharmacokinetic parameters, abbreviated mycophenolic acid area under the concentration-time curve (MPA AUC), or the predose trough concentration on study days 4, 7, 14, 28, or 90. A statistically significant decrease in MPA AUC and increase in oral apparent clearance were observed in renally impaired patients regardless of ethnicity on days 4, and 4 and 7, respectively. The suggested mechanism for these differences is uremia-induced increased MPA free fraction, leading to a temporary increased clearance for this restrictively cleared drug.
Assuntos
Imunossupressores/farmacocinética , Transplante de Rim , Ácido Micofenólico/farmacocinética , Adulto , Idoso , Área Sob a Curva , População Negra , Feminino , Humanos , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , População BrancaRESUMO
The present study was designed to test whether prenatal cocaine (COC) exposure alters sensitivity to the attentional effects of idazoxan (IDZ), an alpha-2 adrenergic antagonist that increases coeruleocortical NE activity. The task assessed subjects' ability to selectively attend to an unpredictable light cue and disregard olfactory distractors. IDZ increased commission errors specifically under conditions of distraction, an effect that was similar in the COC and control groups. In contrast, COC animals were significantly more sensitive than controls to the effects of IDZ on omission errors and nontrials. The pattern of effects suggests that the differential treatment response to IDZ on these latter measures resulted from an alteration in norepinephrine (NE)-modulated dopamine release in the COC animals, reflecting lasting changes in dopaminergic and/or noradrenergic systems as a result of the early cocaine exposure. Based on the behavioral measures that showed a differential response to IDZ in the COC animals, it seems likely that these changes may contribute to the alterations in sustained attention and arousal regulation that have been reported in both animals and humans exposed to cocaine in utero.
Assuntos
Antagonistas Adrenérgicos alfa/farmacologia , Atenção/efeitos dos fármacos , Cocaína/toxicidade , Idazoxano/farmacologia , Animais , Feminino , Injeções Intravenosas , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Desempenho Psicomotor/efeitos dos fármacos , Ratos , Ratos Long-EvansRESUMO
In rats, melanin-concentrating hormone (MCH) neurons are mainly located within the lateral hypothalamic area (LHA). This area is known to be involved in the control of feeding and to contain glucose-sensitive cells. As a role for MCH in the regulation of food intake has been reported, we investigated the effects of 2-deoxyglucose (2DG) on MCH expression in cultured LHA slices, to verify if MCH neurons are sensitive to local glucoprivation through a modulation of MCH synthesis. After a 2-10 h 2DG incubation, competitive reverse transcription-polymerase chain reaction (RT-PCR) did not show any variation of MCH mRNA; no change was also observed in MCH immunocytochemical labeling. A slight decrease of MCH mRNA (5-15%) after a 17 h 2DG treatment might be due to a general degradation of neurons induced by long-term glucoprivation. In conclusion, we suggest that MCH neurons are not the glucose-sensitive cells previously described in the LHA and that the signals inducing their previously reported response to glycemia variations do not arise from the LHA itself.
Assuntos
Desoxiglucose/farmacologia , Hormônios Hipotalâmicos/biossíntese , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Melaninas/biossíntese , Hormônios Hipofisários/biossíntese , Animais , Hormônios Hipotalâmicos/genética , Hipotálamo/química , Imuno-Histoquímica , Melaninas/genética , Melanóforos/metabolismo , Técnicas de Cultura de Órgãos , Hormônios Hipofisários/genética , RNA Mensageiro/análise , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
An increased fetal nuchal translucency detected by first trimester ultrasound has been associated with an elevated risk of aneuploidy. The etiology of the increased nuchal translucency in fetuses with normal chromosomes is uncertain, but it has been associated with poor pregnancy outcome. We report a fetus with increased nuchal translucency and a normal karyotype, in which parvovirus was detected by polymerase chain reaction in the amniotic fluid. Although an ultrasound detected an increased nuchal fold thickness in the second trimester, the pregnancy was otherwise uncomplicated. Parvovirus should be considered as a possible etiology of increased nuchal translucency. The risks to a fetus with first trimester parvovirus infections diagnosed under these conditions are uncertain and require larger studies.