RESUMO
Mitochondria play a major role in the brain. Apart from energy production, mitochondria regulate key factors in the activation of cell signaling pathways such as survival, proliferation, and differentiation. While all these processes occur during the physiological development of the brain, it is surprising that the mitochondrial functions and functioning in the brain during the postnatal development remain poorly explored. In this work, we collected samples of brainstem and cortex of mice at postnatal ages 3 (P3), 21 (P21), and at adulthood (3 months old) and evaluated the mitochondrial oxygen consumption after complex I activation. To do so, we used our oxygraph-2â¯K system (OROBOROS) that measures the mitochondrial bioenergetics in saponin-permeabilized tissue punches of 2⯠mg weight. Furthermore, as sex dimorphism in the brain occurs since very early stages of development, we performed experiments in brain samples of male and female mice. Accordingly, the mitochondrial oxygen consumption rate (OCR) was evaluated under activation of complex I (NADH-linked respiration - mitochondrial state 3), and during the inhibition of the complex V (ATP synthase) with oligomycin (mitochondrial state 4). In following, the respiratory control ratio (RCR - state 3/state4) was calculated as an index of mitochondrial oxidative-phosphorylation coupling. Our results show that the activity of the mitochondrial complex I in the brain increases along with the postnatal development in a sex- and tissue-dependent manner, with males showing higher activity than females, and with brainstem tissue showing higher activity than cortex. Our data may contribute to a better understanding of the sex-dependent maturation of the cortex and the cardiorespiratory network located in the brainstem.
Assuntos
Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Mitocôndrias/metabolismo , NAD/metabolismo , Respiração , Caracteres Sexuais , Animais , Animais Recém-Nascidos , Tronco Encefálico/crescimento & desenvolvimento , Tronco Encefálico/metabolismo , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND AND OBJECTIVES: Perioperative red blood cell transfusions (PBT) may be associated with worse survival. In this study of adults undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), we investigated whether there was an association between PBT and survival. MATERIALS AND METHODS: A retrospective study of adults who had undergone CRS-HIPEC for appendiceal carcinomatosis was conducted. Univariate and multivariate analyses were used to identify factors associated with survival. RESULTS: Of the 270 patients analysed, 170 (63%) received PBT. A PBT was not significantly associated with recurrence-free survival (RFS) (HR = 1·03; 95% CI: 0·7-1·51; P = 0·879) or overall survival (OS) (HR = 0·65; 95% CI: 0·38-1·11; P = 0·116). Higher number of PBT units (≥5) was not associated with worse RFS (P = 0·077) or OS (P = 0·079). Independent predictors of poor survival included as follows: estimated blood loss and high tumour grade for RFS (both P < 0·001), and male gender (P = 0·029) and high tumour grade (P < 0·001) for OS. Higher preoperative haemoglobin was independently associated with better RFS (P = 0·011) and OS (P = 0·006). CONCLUSIONS: In this retrospective study of adults who had undergone CRS-HIPEC for appendiceal carcinomatosis, PBT was not significantly associated with survival.
Assuntos
Neoplasias do Apêndice/terapia , Transfusão de Sangue , Carcinoma/terapia , Procedimentos Cirúrgicos de Citorredução , Hipertermia Induzida , Adulto , Idoso , Análise de Variância , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Apêndice/cirurgia , Perda Sanguínea Cirúrgica , Carcinoma/cirurgia , Quimioterapia do Câncer por Perfusão Regional , Terapia Combinada , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória , Estudos RetrospectivosRESUMO
Electrical impedance spectroscopy, in conjunction with the metal-organic framework (MOF) UiO-66-NH2, is used to detect trace levels of the explosive simulant 2,6-dinitrotoluene. The combination of porosity and functionality of the MOF provides an effective dielectric structure, resulting in changes of impedance magnitude and phase angle. The promising data indicate that MOFs may be used in low-cost, robust explosive detection devices.
RESUMO
Many invertebrates and ectothermic vertebrates successfully cope with a fluctuating supply of ambient oxygen-and consequently, a highly variable tissue oxygenation-through increasing their antioxidant barriers. During chronic deprivation of oxygen, however, the hypometabolic defense mode of the fruit fly Drosophila, the hypoxia-induced behavioral hypothermia of the crayfish Pacifastacus leniusculus, and the production of ethanol during anoxia by the crucian carp Carassius carassius all indicate that these animals are also capable of utilizing a suite of genetic and physiological defenses to survive otherwise lethal reductions in tissue oxygenation. Normally, much of an organism's gene response to hypoxia is orchestrated via the hypoxia-inducible transcription factor HIF. Recent developments expand our view of HIF function even further by highlighting regulatory roles for HIF in the hypometabolism of insects, in the molting and the normoxic immune response of crustaceans, and in the control-via the downstream effector gene erythropoietin-of the hypoxic ventilatory response and pulmonary hypertension in mammals. These and related topics were collectively presented by the authors in a symposium of the 2008 ICA-CBP conference at Mara National Reserve, Kenya, Africa. This synthesis article communicates the essence of the symposium presentations to the wider community.
Assuntos
Adaptação Fisiológica/fisiologia , Fator 1 Induzível por Hipóxia/metabolismo , Hipóxia/fisiopatologia , Estresse Oxidativo/fisiologia , Oxigênio/metabolismo , Animais , Metabolismo Energético/fisiologia , Imunidade Inata/fisiologia , Ventilação Pulmonar/fisiologia , Especificidade da Espécie , TemperaturaRESUMO
Numerous factors involved in general homeostasis are able to modulate respiratory motor output. These include placental-derived steroids, which are necessary for maternal physiological adjustments during gestation, including respiratory stimulation. Despite the fact that these hormones exert potent effects on neural development in the fetus, the hypothesis of a developmental control of the neural respiratory network by placental-derived steroids has been approached experimentally only recently. The objective of this review is to summarize the role and mode of action of placental steroids on respiratory control in adult mammals and highlight the potential pathways by which such steroids are supplied to the developing fetus. Additionally, we present recent results showing that the beta estradiol and progesterone receptors are expressed in the carotid body of newborn male rats, thus supporting the hypothesis of receptor-mediated effect of estradiol and progesterone on carotid bodies.
Assuntos
Hormônios Esteroides Gonadais/metabolismo , Hormônios Placentários/metabolismo , Fenômenos Fisiológicos Respiratórios , Sistema Respiratório/crescimento & desenvolvimento , Animais , Corpo Carotídeo/metabolismo , Feminino , Feto , Humanos , Masculino , Gravidez , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismoRESUMO
The aim of this study is to apply a parsimonious hydrologic model to the Itxina karstic aquifer that can predict changes in discharge resulting from variable inputs (recharge). The Itxina Aquifer was divided into four cells corresponding to different recharge areas. Each cell was treated as a tank to characterize the conditions within the cell. In the model, when the reservoir boundaries coincide with the position of the siphons, the signal simulated is sensitive to input pulses of the recharge. This supports the hypothesis that the siphons are the controlling mechanism in the flow system of the aquifer. The good agreement between predicted and measured discharges demonstrates the ability of the model to simulate the flow in the Itxina Aquifer. These results demonstrated that the hydraulic conductivity increases downstream within the aquifer. The hydraulic conductivities obtained by calibration varied between 4.2 x 10(-3) m/s upstream of the aquifer, 6.0 x 10(-2) m/s in the central region, and 9.5 x 10(-1) m/s in the lower region of the aquifer. These values seem reasonable because the underground features in the principal caves show that the density of caves increases downstream in the Itxina Aquifer. The simple representation of the system produced results comparable to traditional ground water models with fewer data requirements and calibration parameters.
Assuntos
Abastecimento de Água , Fenômenos Geológicos , Geologia , Modelos Teóricos , Permeabilidade , Espanha , Poluição Química da ÁguaRESUMO
The effect of chronic hypoxia on gender differences in physiology and neurochemistry of chemosensory pathways was studied in prepubertal and adult rats living at sea level (SL; Lyon, France) or at high altitude (HA; La Paz, Bolivia, 3,600 m). HA adult rats had higher hematocrit (Ht%), Hb concentration, resting ventilatory rate (Ve(100)), and higher tyrosine hydroxylase (TH) activity in carotid bodies (CB) than SL animals. At HA and SL, adult females had lower Ht% (46.0 +/- 0.8 vs. 50.4 +/- 0.6% at HA, P < 0.05 and 43.8 +/- 0.9 vs. 47.1 +/- 0.8% at SL, P < 0.05) and Hb (16.1 +/- 0.3 vs. 17.7 +/- 0.2 g/dl at HA, P < 0.05 and 14.5 +/- 0.3 vs. 15.6 +/- 0.1 g/dl at SL, P < 0.05) than males. Females had higher Ve(100) [170 +/- 19 vs. 109 +/- 7 ml. min(-1). 100 g(-1) at HA, P < 0.05 and 50 +/- 3 vs. 40 +/- 2 ml. min(-1). 100 g(-1) at SL, not significant (NS)] and lower CB-TH activity (1.40 +/- 0.2 vs. 3.87 +/- 0.6 pmol/20 min at HA, P < 0.05 and 0.52 +/- 0.1 vs. 0.68 +/- 0.1 pmol/20 min at SL; NS) than males at HA only. The onset of hypoxic ventilatory response during development was delayed at HA. Prepubertal HA females had higher Ve(100) than males (2 wk old, +47%) and higher CB-TH activity (3 wk old, +51%). Medullary noradrenergic groups were sex dimorphic during development at SL. Rats raised at HA had a drop of TH activity between the second and the third postnatal week in all medullary groups. In conclusion, our data support the hypothesis that the CB is the major site for sexual differentiation of the ventilatory control. Ventilatory differences appeared before puberty, and the animals bred at HA had profound alterations in the developmental process of the chemoreflex and its neural pathways. Some of these alterations are under dependence of the sex of the animal, and there is an important interaction between gender and the hypoxic environmental condition during the developmental period.