Captivity affects mitochondrial aerobic respiration and carotenoid metabolism in the house finch (Haemorhous mexicanus).

In many species of animals, red carotenoid-based coloration is produced by metabolizing yellow dietary pigments, and this red ornamentation can be an honest signal of individual quality. However, the physiological basis for associations between organism function and the metabolism of red ornamental carotenoids from yellow dietary carotenoids remains uncertain. A recent hypothesis posits that carotenoid metabolism depends on mitochondrial performance, with diminished red coloration resulting from altered mitochondrial aerobic respiration. To test for an association between mitochondrial respiration and red carotenoids, we held wild-caught, molting male house finches in either small bird cages or large flight cages to create environmental challenges during the period when red ornamental coloration is produced. We predicted that small cages would present a less favorable environment than large flight cages and that captivity itself would decrease both mitochondrial performance and the abundance of red carotenoids compared with free-living birds. We found that captive-held birds circulated fewer red carotenoids, showed increased mitochondrial respiratory rates, and had lower complex II respiratory control ratios - a metric associated with mitochondrial efficiency - compared with free-living birds, though we did not detect a difference in the effects of small cages versus large cages. Among captive individuals, the birds that circulated the highest concentrations of red carotenoids had the highest mitochondrial respiratory control ratio for complex II substrate. These data support the hypothesis that the metabolism of red carotenoid pigments is linked to mitochondrial aerobic respiration in the house finch, but the mechanisms for this association remain to be established.

Duration and Consequences of Periodic Breathing in Infants Born Preterm Before and After Hospital Discharge.

OBJECTIVE: To investigate the amount of time spent in periodic breathing and its consequences in infants born preterm before and after hospital discharge. METHODS: Infants born preterm between 28-32 weeks of gestational age were studied during daytime sleep in the supine position at 32-36 weeks of postmenstrual age (PMA), 36-40 weeks of PMA, and 3 months and 6 months of corrected age. The percentage of total sleep time spent in periodic breathing (% total sleep time periodic breathing) was calculated and infants were grouped into below and above the median (8.5% total sleep time periodic breathing) at 32-36 weeks and compared with 36-40 weeks, 3 and 6 months. RESULTS: Percent total sleep time periodic breathing was not different between 32-36 weeks of PMA (8.5%; 1.5, 15.0) (median, IQR) and 36-40 weeks of PMA (6.6%; 0.9, 15.1) but decreased at 3 (0.4%; 0.0, 2.0) and 6 months of corrected age 0% (0.0, 1.1). Infants who spent above the median % total sleep time periodic breathing at 32-36 weeks of PMA spent more % total sleep time periodic breathing at 36-40 weeks of PMA (18.1%; 7.7, 23.9 vs 2.1%; 0.6, 6.4) and 6 months of corrected age 0.9% (0.0, 3.3) vs 0.0% (0.0, 0.0). CONCLUSIONS: Percentage sleep time spent in periodic breathing did not decrease as infants born preterm approached term corrected age, when they were to be discharged home. High amounts of periodic breathing at 32-36 weeks of PMA was associated with high amounts of periodic breathing at term corrected age (36-40 weeks of PMA), and persistence of periodic breathing at 6 months of corrected age.

Transgenic rodents as dynamic models for the study of respiratory rhythm generation and modulation: a scoping review and a bibliometric analysis.

The pre-Bötzinger complex, situated in the ventrolateral medulla, serves as the central generator for the inspiratory phase of the respiratory rhythm. Evidence strongly supports its pivotal role in generating, and, in conjunction with the post-inspiratory complex and the lateral parafacial nucleus, in shaping the respiratory rhythm. While there remains an ongoing debate concerning the mechanisms underlying these nuclei's ability to generate and modulate breathing, transgenic rodent models have significantly contributed to our understanding of these processes. However, there is a significant knowledge gap regarding the spectrum of transgenic rodent lines developed for studying respiratory rhythm, and the methodologies employed in these models. In this study, we conducted a scoping review to identify commonly used transgenic rodent lines and techniques for studying respiratory rhythm generation and modulation. Following PRISMA guidelines, we identified relevant papers in PubMed and EBSCO on 29 March 2023, and transgenic lines in Mouse Genome Informatics and the International Mouse Phenotyping Consortium. With strict inclusion and exclusion criteria, we identified 80 publications spanning 1997-2022 using 107 rodent lines. Our findings revealed 30 lines focusing on rhythm generation, 61 on modulation, and 16 on both. The primary in vivo method was whole-body plethysmography. The main in vitro method was hypoglossal/phrenic nerve recordings using the en bloc preparation. Additionally, we identified 119 transgenic lines with the potential for investigating the intricate mechanisms underlying respiratory rhythm. Through this review, we provide insights needed to design more effective experiments with transgenic animals to unravel the mechanisms governing respiratory rhythm. The identified transgenic rodent lines and methodological approaches compile current knowledge and guide future research towards filling knowledge gaps in respiratory rhythm generation and modulation.

Myorelaxation, respiratory depression and electrocardiographic changes caused by the administration of extract of açai (Euterpe oleracea Mart.) stone in rats.

The biological and pharmacological properties of natural polyphenols of the extract of Euterpe oleracea stone (EEOS) are associated with the central nervous system (CNS). To investigate the sedative and myorelaxant activity of EEOS in vivo, this study aimed to present the myorelaxant and sedative effects of EEOS in Wistar rats using spontaneous locomotor activity and motor electrophysiology. A total of 108 animals were used in the following experiments: a) behavioral tests (n = 27); b) electromyographic recordings of skeletal muscle (n = 27); c) respiratory muscle activity recordings (n = 27); d) cardiac muscle activity recordings (n = 27). The behavioral characteristics were measured according to the latency time of onset, the transient loss of posture reflex and maximum muscle relaxation. Electrodes were implanted in the gastrocnemius muscle and in the tenth intercostal space for electromyographic (EMG) signal capture to record muscle contraction, and in the D2 lead for electrocardiogram acquisition. After using the 300 mg/kg dose of EEOS intraperitoneally, a myorelaxant activity exhibited a lower frequency of contractility with an amplitude pattern of low and short duration at gastrocnemius muscle and intercostal muscle, which clearly describes a myorelaxant activity and changes in cardiac activity. The present report is so far the first study to demonstrate the myorelaxant activity of this extract, indicating an alternative route for açai stone valorization and its application in pharmaceutical fields.

Orexin-A inhibits fictive air breathing responses to respiratory stimuli in the bullfrog tadpole (Lithobates catesbeianus).

In pre-metamorphic tadpoles, the neural network generating lung ventilation is present but actively inhibited; the mechanisms leading to the onset of air breathing are not well understood. Orexin (ORX) is a hypothalamic neuropeptide that regulates several homeostatic functions, including breathing. While ORX has limited effects on breathing at rest, it potentiates reflexive responses to respiratory stimuli mainly via ORX receptor 1 (OX1R). Here, we tested the hypothesis that OX1Rs facilitate the expression of the motor command associated with air breathing in pre-metamorphic bullfrog tadpoles (Lithobates catesbeianus). To do so, we used an isolated diencephalic brainstem preparation to determine the contributions of OX1Rs to respiratory motor output during baseline breathing, hypercapnia and hypoxia. A selective OX1R antagonist (SB-334867; 5-25 µmol l-1) or agonist (ORX-A; 200 nmol l-1 to 1 µmol l-1) was added to the superfusion media. Experiments were performed under basal conditions (media equilibrated with 98.2% O2 and 1.8% CO2), hypercapnia (5% CO2) or hypoxia (5-7% O2). Under resting conditions gill, but not lung, motor output was enhanced by the OX1R antagonist and ORX-A. Hypercapnia alone did not stimulate respiratory motor output, but its combination with SB-334867 increased lung burst frequency and amplitude, lung burst episodes, and the number of bursts per episode. Hypoxia alone increased lung burst frequency and its combination with SB-334867 enhanced this effect. Inactivation of OX1Rs during hypoxia also increased gill burst amplitude, but not frequency. In contrast with our initial hypothesis, we conclude that ORX neurons provide inhibitory modulation of the CO2 and O2 chemoreflexes in pre-metamorphic tadpoles.

Role of SARS-CoV-2 neurotropism and neuroinvasion in COVID-19 patients disease severity.

The disease caused by the new SARS-CoV-2 coronavirus (COVID-19) spread rapidly from China to the entire world. Approximately one third of SARS-CoV-2-infected patients have neurological disorders, especially those classified as severe cases and that require mechanical ventilation. On the other hand, almost nine out of 10 patients admitted to an Intensive Care Unit could not breathe spontaneously, thus requiring invasive and non-invasive ventilatory support. So far, whether early neurological disorders such as hyposmia or anosmia, dysgeusia or ageusia, headache and vertigo are significant in the progression to the severe form of the disease or whether they are related to entry to the central nervous system via peripheral nerves has not been determined. Considering the great similarity between SARS-CoV and SARS-CoV-2, and that the severity of the condition that leads to death cannot be explained solely by lung involvement, it is important to determine whether SARS-CoV-2 potential invasion to the central nervous system is partially responsible for the severe respiratory component observed in patients with COVID-19.

La enfermedad (COVID-19) producida por el nuevo coronavirus SARS-CoV-2 se extendió rápidamente desde China a todo el mundo. Aproximadamente una tercera parte de los pacientes infectados de SARS-CoV-2 presenta alteraciones neurológicas, con mayor frecuencia los clasificados como graves que requirieron ventilación mecánica. Por otro lado, casi nueve de cada 10 pacientes admitidos en una unidad de cuidados intensivos no podían respirar espontáneamente, por lo que ameritaron apoyo ventilatorio invasivo y no invasivo. Hasta el momento no se ha determinado si las alteraciones neurológicas tempranas como la hiposmia o anosmia, disgeusia o ageusia, cefalea y vértigo son significativas en la progresión a la forma grave de la enfermedad y se relacionan con la entrada al sistema nervioso central a través de los nervios periféricos. Considerando la gran similitud entre SARS-CoV y SARS-CoV-2 y que la severidad del cuadro que conduce a la muerte no puede ser explicado únicamente por la afección pulmonar, es importante determinar si la invasión potencial del SARS-CoV-2 al sistema nervioso central es parcialmente responsable del componente respiratorio severo que presentan los pacientes con COVID-19.

Role of SARS-CoV-2 neurotropism and neuroinvasion in COVID-19 patients disease severity / Papel del neurotropismo y neuroinvasión de SARS-CoV-2 en la gravedad de los pacientes con COVID-19

Abstract The disease caused by the new SARS-CoV-2 coronavirus (COVID-19) spread rapidly from China to the entire world. Approximately one third of SARS-CoV-2-infected patients have neurological disorders, especially those classified as severe cases and that require mechanical ventilation. On the other hand, almost nine out of 10 patients admitted to an Intensive Care Unit could not breathe spontaneously, thus requiring invasive and non-invasive ventilatory support. So far, whether early neurological disorders such as hyposmia or anosmia, dysgeusia or ageusia, headache and vertigo are significant in the progression to the severe form of the disease or whether they are related to entry to the central nervous system via peripheral nerves has not been determined. Considering the great similarity between SARS-CoV and SARS-CoV-2, and that the severity of the condition that leads to death cannot be explained solely by lung involvement, it is important to determine whether SARS-CoV-2 potential invasion to the central nervous system is partially responsible for the severe respiratory component observed in patients with COVID-19.

Resumen La enfermedad (COVID-19) producida por el nuevo coronavirus SARS-CoV-2 se extendió rápidamente desde China a todo el mundo. Aproximadamente una tercera parte de los pacientes infectados de SARS-CoV-2 presenta alteraciones neurológicas, con mayor frecuencia los clasificados como graves que requirieron ventilación mecánica. Por otro lado, casi nueve de cada 10 pacientes admitidos en una unidad de cuidados intensivos no podían respirar espontáneamente, por lo que ameritaron apoyo ventilatorio invasivo y no invasivo. Hasta el momento no se ha determinado si las alteraciones neurológicas tempranas como la hiposmia o anosmia, disgeusia o ageusia, cefalea y vértigo son significativas en la progresión a la forma grave de la enfermedad y se relacionan con la entrada al sistema nervioso central a través de los nervios periféricos. Considerando la gran similitud entre SARS-CoV y SARS-CoV-2 y que la severidad del cuadro que conduce a la muerte no puede ser explicado únicamente por la afección pulmonar, es importante determinar si la invasión potencial del SARS-CoV-2 al sistema nervioso central es parcialmente responsable del componente respiratorio severo que presentan los pacientes con COVID-19.

Procedures of Mitochondria Purification and Gene Expression to Study Alternative Respiratory and Uncoupling Pathways in Fruits.

We describe detailed procedures to get intact and well-coupled mitochondria from a variety of fruit species such as papaya (Carica papaya), guava (Psidium guajava), tomato (Solanum lycopersicum), and strawberry (Fragaria x ananassa) as well as the protocols to assess the capacities of AOX and UCP pathways in intact fruit mitochondria. The procedures presented here were tested for the species mentioned above; their use with other types of fruits must be tested for yield of intact and active mitochondria. This is possible from individual adjustments. Strict care during extraction, including the use of osmotic protectants (i.e., mannitol/sucrose) and antioxidants (i.e., cysteine, ascorbate) at defined concentrations, are critical factors to ensure mitochondrial integrity and to obtain higher yields. The mitochondria purified using the discontinuous Percoll gradients described here can be used for the analysis of the capacity of alternative respiration and uncoupling pathways in fruits. In addition, protocols for quantitative and semiquantitative PCR applicable for the analysis of AOX and UCP gene expression in fruits are shown. Microarray and RNA-seq data from public databases are also valuable for the analysis of AOX and UCP genes. In both cases having the sequences of genes or cDNAs to be used in primer design or probe identification is necessary.

Liver mitochondrial membrane fluidity at early development of diabetes and its correlation with the respiration.

The biological membranes are important in cell function but, during development of diseases such as diabetes, they are impaired. Consequently, membrane-associated biological processes are impaired as well. The mitochondria are important organelles where oxidative phosphorylation takes place, a process closely related with the membranes. In general, it is accepted that the development process of diabetes decreases membrane fluidity. However, in some cases, it has been found to increase membrane fluidity of mitochondria but to decrease the Respiratory Control (RC) index. In this study we found an increase of membrane fluidity and an increase of the RC at an early phase of the development of a type 2 diabetes model. We measured the lipoperoxidation, analyzed the fatty acids composition by gas chromatography, and assessed membrane fluidity using three fluorescent monitors located at different depths inside the bilayer, dipyrenilpropane (DPyP), diphenylhexatriene (DPH), and trimethylammonium diphenylhexatriene (TMA-DPH). Our findings indicate that in the initial stage of diabetes development, when lipoperoxidation still is not significant, the membrane fluidity of liver mitochondria increases because of the increment in the unsaturated to saturated fatty acids ratio (U/S), thus producing an increase of the RC. The membrane fluidity is not the same at all depths in the bilayer. Contrary to the results obtained in mitochondria, the diabetes induced a decrease in the U/S fatty acids ratio of liver total lipids, indicating that the mitochondria might have an independent mechanism for regulating its fatty acids composition.

Changes in cardiovascular responses to chemoreflex activation of rats recovered from protein restriction are not related to AT1 receptors.

NEW FINDINGS: What is the central question of this study? In this study, we sought to investigate whether cardiovascular responses to peripheral chemoreflex activation of rats recovered from protein restriction are related to activation of AT1 receptors. What is the main finding and its importance? This study highlights the fact that angiotensinergic mechanisms activated by AT1 receptors do not support increased responses to peripheral chemoreflex activation by KCN in rats recovered from protein restriction. Also, we found that protein restriction led to increased resting ventilation in adult rats, even after recovery. The effects of a low-protein diet followed by recovery on cardiorespiratory responses to peripheral chemoreflex activation were tested before and after systemic angiotensin II type 1 (AT1 ) receptor antagonism. Male Fischer rats were divided into control and recovered (R-PR) groups after weaning. The R-PR rats were fed a low-protein (8%) diet for 35 days and recovered with a normal protein (20%) diet for 70 days. Control rats received a normal protein diet for 105 days (CG105 ). After cannulation surgery, mean arterial pressure, heart rate, respiratory frequency, tidal volume and minute ventilation were acquired using a digital recording system in freely moving rats. The role of angintensin II was evaluated by systemic antagonism of AT1 receptors with losartan (20 mg kg-1 i.v.). The peripheral chemoreflex was elicited by increasing doses of KCN (20-160 µg kg min-1 , i.v.). At baseline, R-PR rats presented increased heart rate and minute ventilation (372 ± 34 beats min-1 and 1.274 ± 377 ml kg-1  min-1 ) compared with CG105 animals (332 ± 22 beats min-1 and 856 ± 112 ml kg-1  min-1 ). Mean arterial pressure was not different between the groups. Pressor and bradycardic responses evoked by KCN (60 µg kg-1 ) were increased in R-PR (+45 ± 13 mmHg and -77 ± 47 beats min-1 ) compared with CG105 rats (+25 ± 17 mmHg and -27 ± 28 beats min-1 ), but no difference was found in the tachypnoeic response. These differences were preserved after losartan. The data suggest that angiotensin II acting on AT1 receptors may not be associated with the increased heart rate, increased minute ventilation and acute cardiovascular responses to peripheral chemoreflex activation in rats that underwent postweaning protein restriction followed by recovery.

HIF1α and physiological responses to hypoxia are correlated in mice but not in rats.

We previously reported that rats and mice that have been raised for more than 30 generations in La Paz, Bolivia (3600 m), display divergent physiological responses to high altitude, including improved respiratory and metabolic control in mice. In the present study, we asked whether these traits would also be present in response to hypoxia at sea level. To answer this question, we exposed rats (Sprague Dawley) and mice (FVB) to normoxia (21% O2) or hypoxia (15 and 12% O2) for 6 h and measured ventilation and metabolic rate (whole-body plethysmography), and expression of the transcription factor HIF-1α (ELISA and mass spectrometry) and other proteins whose expression are regulated by hypoxia (glucose transporter 1, pyruvate dehydrogenase kinase 1 and angiopoietin 2; mass spectrometry) in the brainstem. In response to hypoxia, compared with rats, mice had higher minute ventilation, lower metabolic rate and higher expression of HIF-1α in the brainstem. In mice, the expression level of HIF-1α was positively correlated with ventilation and negatively correlated with metabolic rate. In rats, the concentration of brainstem cytosolic protein decreased by 38% at 12% O2, while expression of the glucose transporter 1 increased. We conclude that mice and rats raised at sea level have divergent physiological and molecular responses to hypoxia, supporting the hypothesis that mice have innate traits that favor adaptation to altitude.

Ventilatory Responses to Hypercarbia in Infants of Mothers Who Smoke and Misuse Substances.

The ventilatory response of infants of mothers who smoke and misuse substances and controls to carbon dioxide was assessed at 6-12 weeks and the perinatal period. Infants of mothers who smoke and misuse substances had a dampened response at the peak age of sudden infant death syndrome, greater than in the perinatal period.

Adaptation to Life in the High Andes: Nocturnal Oxyhemoglobin Saturation in Early Development.

STUDY OBJECTIVES: Physiological adaptation to high altitude hypoxia may be impaired in Andeans with significant European ancestry. The respiratory 'burden' of sleep may challenge adaptation, leading to relative nocturnal hypoxia. Developmental aspects of sleep-related breathing in high-altitude native children have not previously been reported. We aimed to determine the influence of development on diurnal-nocturnal oxyhemoglobin differences in children living at high altitude. METHODS: This was a cross-sectional, observational study. Seventy-five healthy Bolivian children aged 6 mo to 17 y, native to low altitude (500 m), moderate high altitude (2,500 m), and high altitude (3,700 m) were recruited. Daytime resting pulse oximetry was compared to overnight recordings using Masimo radical oximeters. Genetic ancestry was determined from DNA samples. RESULTS: Children had mixed European/Amerindian ancestry, with no significant differences between altitudes. Sixty-two participants had ≥ 5 h of nocturnal, artifact-free data. As predicted, diurnal mean oxyhemoglobin saturation decreased across altitudes (infants and children, both P < 0.001), with lowest diurnal values at high altitude in infants. At high altitude, there was a greater drop in nocturnal mean oxyhemoglobin saturation (infants, P < 0.001; children, P = 0.039) and an increase in variability (all P ≤ 0.001) compared to low altitude. Importantly, diurnal to nocturnal altitude differences diminished (P = 0.036), from infancy to childhood, with no further change during adolescence. CONCLUSIONS: Physiological adaptation to high-altitude living in native Andeans is unlikely to compensate for the significant differences we observed between diurnal and nocturnal oxyhemoglobin saturation, most marked in infancy. This vulnerability to sleep-related hypoxia in early childhood has potential lifespan implications. Future studies should characterize the sleep- related respiratory physiology underpinning our observations.

New Insights on the Maternal Diet Induced-Hypertension: Potential Role of the Phenotypic Plasticity and Sympathetic-Respiratory Overactivity.

Systemic arterial hypertension (SAH) is an important risk factor for cardiovascular disease and affects worldwide population. Current environment including life style coupled with genetic programming have been attributed to the rising incidence of hypertension. Besides, environmental conditions during perinatal development such as maternal malnutrition can program changes in the integration among renal, neural, and endocrine system leading to hypertension. This phenomenon is termed phenotypic plasticity and refers to the adjustment of a phenotype in response to environmental stimuli without genetic change, following a novel or unusual input during development. Human and animal studies indicate that fetal exposure to an adverse maternal environment may alter the renal morphology and physiology that contribute to the development of hypertension. Recently, it has been shown that the maternal protein restriction alter the central control of SAH by a mechanism that include respiratory dysfunction and enhanced sympathetic-respiratory coupling at early life, which may contribute to adult hypertension. This review will address the new insights on the maternal diet induced-hypertension that include the potential role of the phenotypic plasticity, specifically the perinatal protein malnutrition, and sympathetic-respiratory overactivity.

Evolution and physiology of neural oxygen sensing.

Major evolutionary trends in animal physiology have been heavily influenced by atmospheric O2 levels. Amongst other important factors, the increase in atmospheric O2 which occurred in the Pre-Cambrian and the development of aerobic respiration beckoned the evolution of animal organ systems that were dedicated to the absorption and transportation of O2, e.g., the respiratory and cardiovascular systems of vertebrates. Global variations of O2 levels in post-Cambrian periods have also been correlated with evolutionary changes in animal physiology, especially cardiorespiratory function. Oxygen transportation systems are, in our view, ultimately controlled by the brain related mechanisms, which senses changes in O2 availability and regulates autonomic and respiratory responses that ensure the survival of the organism in the face of hypoxic challenges. In vertebrates, the major sensorial system for oxygen sensing and responding to hypoxia is the peripheral chemoreflex neuronal pathways, which includes the oxygen chemosensitive glomus cells and several brainstem regions involved in the autonomic regulation of the cardiovascular system and respiratory control. In this review we discuss the concept that regulating O2 homeostasis was one of the primordial roles of the nervous system. We also review the physiology of the peripheral chemoreflex, focusing on the integrative repercussions of chemoreflex activation and the evolutionary importance of this system, which is essential for the survival of complex organisms such as vertebrates. The contribution of hypoxia and peripheral chemoreflex for the development of diseases associated to the cardiovascular and respiratory systems is also discussed in an evolutionary context.

α-Tocopherol administration blocks adaptive changes in cell NADH/NAD+ redox state and mitochondrial function leading to inhibition of gastric mucosa cell proliferation in rats.

In experimentally induced chronic gastritis, a compensatory mucosal cell proliferation occurs with enhanced glucose oxidative metabolism linked to lipoperoxidative events. Therefore, this study was aimed at assessing the participation of cell NAD/NADH redox state and mitochondrial functions during gastric mucosa proliferation and the effects of in vivo α-tocopherol (vitamin E) administration. Glucose oxidation and oxygen consumption were tested in gastric mucosa samples obtained from rats with gastritis and from those also treated with α-tocopherol. Gastric mucosal mitochondria were isolated and structural and functional parameters were determined. Succinate oxidation, ADP phosphorylation, mitochondrial enzyme activities, and membrane lipid composition were measured. In addition, parameters indicative of cellular NAD/NADH redox state, proliferation, apoptosis, and nitric oxide (NO) metabolism were also determined. After ethanol withdrawal, the damaged gastric mucosa increased glucose and oxygen consumption, events associated with a more reduced cytoplasmic NAD/NADH ratio. Enhanced mitochondrial oxidative phosphorylation and increased mitochondrial enzyme activities occurred early, accompanied by recovery of lost mitochondrial protein and lipid composition in the gastric mucosa, events associated with increased NO production. When mitochondrial function and structural events were normalized, apoptosis was initiated as assessed by the mitochondrial Bax/Bcl2 ratio. Treatment with α-tocopherol inhibited cell proliferation and blocked enhanced glucose utilization, mitochondrial substrate oxidation, and changes in redox state, delaying the onset of these adaptive metabolic changes, whereas it inhibited cell proliferation. In conclusion, α-tocopherol could abolish damage-induced "stress" signaling by desynchronizing mitochondrial adaptive responses, including mitochondria biogenesis, and consequently NAD/NADH redox, which seems to regulate gastric mucosal cell proliferation.

Modulation of mitochondrial functions by the indirect antioxidant sulforaphane: a seemingly contradictory dual role and an integrative hypothesis.

The chemotherapeutic isothiocyanate sulforaphane (SFN) was early linked to anticarcinogenic and antiproliferative activities. Soon after, this compound, derived from cruciferous vegetables, became an excellent and useful trial for anti-cancer research in experimental models including growth tumor, metastasis, and angiogenesis. Many subsequent reports showed modifications in mitochondrial signaling, functionality, and integrity induced by SFN. When cytoprotective effects were found in toxic and ischemic insult models, seemingly contradictory behaviors of SFN were discovered: SFN was inducing deleterious changes in cancer cell mitochondria that eventually would carry the cell to death via apoptosis and also was protecting noncancer cell mitochondria against oxidative challenge, which prevented cell death. In both cases, SFN exhibited effects on mitochondrial redox balance and phase II enzyme expression, mitochondrial membrane potential, expression of the family of B cell lymphoma 2 homologs, regulation of proapoptotic proteins released from mitochondria, activation/inactivation of caspases, mitochondrial respiratory complex activities, oxygen consumption and bioenergetics, mitochondrial permeability transition pore opening, and modulation of some kinase pathways. With the ultimate findings related to the induction of mitochondrial biogenesis by SFN, it could be considered that SFN has effects on mitochondrial dynamics that explain some divergent points. In this review, we list the reports involving effects on mitochondrial modulation by SFN in anti-cancer models as well as in cytoprotective models against oxidative damage. We also attempt to integrate the data into a mechanism explaining the various effects of SFN on mitochondrial function in only one concept, taking into account mitochondrial biogenesis and dynamics and making a comparison with the theory of reactive oxygen species threshold of cell death. Our interest is to achieve a complete view of cancer and protective therapies based on SFN that can be extended to other chemotherapeutic compounds with similar characteristics. The work needed to test this hypothesis is quite extensive.

Mitochondrial dysfunction in the hippocampus of rats caused by chronic oxidative stress.

The aim of this study was to analyze the effects of chronic oxidative stress on mitochondrial function and its relationship to progressive neurodegeneration in the hippocampus of rats chronically exposed to ozone. Animals were exposed to 0.25 ppm ozone for 7, 15, 30, or 60 days. Each group was tested for (1) protein oxidation and, manganese superoxide dismutase (Mn-SOD), glutathione peroxidase (GPx) and succinate dehydrogenase (SDH) activity using spectrophotometric techniques, (2) oxygen consumption, (3) cytochrome c, inducible nitric oxide synthase (iNOS), peroxisome proliferator-activated receptor γ Co-activator 1α (PGC-1α), B-cell lymphoma (Bcl-2), and Bax expression using Western blotting, (4) histology using hematoxylin and eosin staining, and (5) mitochondrial structure using electron microscopy. Our results showed increased levels of carbonyl protein and Mn-SOD activity after 30 days of ozone exposure and decreased GPx activity. The SDH activity decreased from 7 to 60 days of exposure. The oxygen consumption decreased at 60 days. Western blotting showed an increase in cytochrome c at 60 days of ozone exposure and an increase in iNOS up to 60 days of ozone exposure. The expression of PGC-1α was decreased after 15, 30, and 60 days compared to the earlier time Bcl-2 was increased at 60 days compared to earlier time points, and Bax was increased after 30 and 60 days of exposure compared to earlier time points. We observed cellular damage, and mitochondrial swelling with a loss of mitochondrial cristae after 60 days of exposure. These changes suggest that low doses of ozone caused mitochondrial abnormalities that may lead to cell damage.

Un modelo anfibio para el estudio evolutivo del control respiratorio / Anphibian model study for evolutionary respiratory control

Los enormes progresos de la medicina perinatal han permitido la sobrevivencia de recién nacidos prematuros en estadios de desarrollo cada vez más precoces. Estos pequeños pacientes requieren de medios muy sofisticados y costosos para paliar su inmadurez respiratoria. Además de las complicaciones asociadas al desarrollo pulmonar, la inestabilidad respiratoria y las apneas asociadas a la inmadurez de los circuitos nerviosos productores del control respiratorio, contribuyendo éstos últimas, como factor principal de morbilidad, a las prolongadas hospitalizaciones que presenta esta tan vulnerable población. Éstos imperativos médicos combinados a la curiosidad fisiológica han contribuido al desenvolvimiento de novedosas investigaciones en neurobiología respiratoria. Si bien la mayoría de los trabajos realizados en éste campo utilizan a los múridos como modelos experimentales, las investigaciones recientes efectuadas a partir del tronco cerebral aislado de anfibios (Rana catesbeiana) han revelado las ventajas técnicas de este modelo animal, para mostrar los principales fenómenos que rigen el funcionamiento y el desarrollo del sistema de control respiratorio entre los vertebrados. El presente artículo se propone repasar los avances más recientes realizados en la investigación de la neurobiología evolutiva del control respiratorio, prestando una atención particular a la respiración episódica, así como al rol que desempeñan la modulación serotoninérgica y Gabaérgica de la actividad respiratoria en el curso del desarrollo.

Recent perinal advances have made possible that premature newborns survive increasingtly in earlier developmental stages. This babies requires sophisticated and costly critical intensive care to address the problems associated with inmadurity of the respiratory system. In addition respiratory instability and apnea reflecting inmaturity of the respiratory control system are major causes of morbidity and prolonged hospitalization in this highly vulnerable group of patients. These concerns have contributed to the development of research in respiratoy evolutionary neurobiology. While the majority of researchers working in this field use rodents as an animal model, recent research using in vitro brainstem preparations from bullfrog (Rana catesbeiana) have reveled the technical advantages of this model to study the basic principles underlying respiratory control and its ontogeny between vertebrates. The present article review the recent advances in the area of research with special interest on episodic breathing and the role of serotoninergic and GABAergic modulation of respiratory control during development.

EFEITOS DO PRÉ-CONDICIONAMENTO HEPÁTICO EM RATOS CIRRÓTICOS, SUBMETIDOS À ISQUEMIA E REPERFUSÃO HEPÁTICA RESULTADOS PRELIMINARES

We studied the influence of ischemic preconditioning in rat liver cirrhosis.The cirrhosis were induced in wistar rat with occlusion of biliary duct before 30 days operation and divided into group A, ischemic preconditioning and ischemic/reperfusion, and group B, only ischemic/reperfusion. In group A the preconditioning consisted of 5 min ischemic and 10 min reperfusion. The ischemic/reperfusion consisted of 20 min ischemic and 120 min reperfusion for both groups. The level of respiratory control reason (RCR) in the liver tissue 120 min after reperfusion was not difference significantly in the groups. Therefore it suggests that the preconditioning cam be viability and another object of studies must be rated in future this work.

Baseando-se nos efeitos estimuladores do metabolismo energético pelo pré-condicionamento isquêmico (PCI) no tecido hepático, estudou-se dois grupos de ratos cirróticos submetidos a isquemia de 20 min e reperfusão de 120 min, após o PCI ou não respectivamente, determinando assim o valor do seu uso no prolongamento da manobra de Pringle e na regeneração hepática na hepatectomia.