Science.gov

Sample records for acute severe hypoxia

  1. Muscle Activation During Exercise in Severe Acute Hypoxia: Role of Absolute and Relative Intensity

    PubMed Central

    Torres-Peralta, Rafael; Losa-Reyna, José; González-Izal, Miriam; Perez-Suarez, Ismael; Calle-Herrero, Jaime; Izquierdo, Mikel

    2014-01-01

    Abstract Torres-Peralta, Rafael, José Losa-Reyna, Miriam González-Izal, Ismael Perez-Suarez, Jaime Calle-Herrero, Mikel Izquierdo, and José A.L. Calbet. Muscle activation during exercise in severe acute hypoxia: Role of absolute and relative intensity. High Alt Med Biol 15:472–482, 2014.—The aim of this study was to determine the influence of severe acute hypoxia on muscle activation during whole body dynamic exercise. Eleven young men performed four incremental cycle ergometer tests to exhaustion breathing normoxic (FIo2=0.21, two tests) or hypoxic gas (FIo2=0.108, two tests). Surface electromyography (EMG) activities of rectus femoris (RF), vastus medialis (VL), vastus lateralis (VL), and biceps femoris (BF) were recorded. The two normoxic and the two hypoxic tests were averaged to reduce EMG variability. Peak Vo2 was 34% lower in hypoxia than in normoxia (p<0.05). The EMG root mean square (RMS) increased with exercise intensity in all muscles (p<0.05), with greater effect in hypoxia than in normoxia in the RF and VM (p<0.05), and a similar trend in VL (p=0.10). At the same relative intensity, the RMS was greater in normoxia than in hypoxia in RF, VL, and BF (p<0.05), with a similar trend in VM (p=0.08). Median frequency increased with exercise intensity (p<0.05), and was higher in hypoxia than in normoxia in VL (p<0.05). Muscle contraction burst duration increased with exercise intensity in VM and VL (p<0.05), without clear effects of FIo2. No significant FIo2 effects on frequency domain indices were observed when compared at the same relative intensity. In conclusion, muscle activation during whole body exercise increases almost linearly with exercise intensity, following a muscle-specific pattern, which is adjusted depending on the FIo2 and the relative intensity of exercise. Both VL and VM are increasingly involved in power output generation with the increase of intensity and the reduction in FIo2. PMID:25225839

  2. Muscle activation during exercise in severe acute hypoxia: role of absolute and relative intensity.

    PubMed

    Torres-Peralta, Rafael; Losa-Reyna, José; González-Izal, Miriam; Perez-Suarez, Ismael; Calle-Herrero, Jaime; Izquierdo, Mikel; Calbet, José A L

    2014-12-01

    The aim of this study was to determine the influence of severe acute hypoxia on muscle activation during whole body dynamic exercise. Eleven young men performed four incremental cycle ergometer tests to exhaustion breathing normoxic (FIO2=0.21, two tests) or hypoxic gas (FIO2=0.108, two tests). Surface electromyography (EMG) activities of rectus femoris (RF), vastus medialis (VL), vastus lateralis (VL), and biceps femoris (BF) were recorded. The two normoxic and the two hypoxic tests were averaged to reduce EMG variability. Peak VO2 was 34% lower in hypoxia than in normoxia (p<0.05). The EMG root mean square (RMS) increased with exercise intensity in all muscles (p<0.05), with greater effect in hypoxia than in normoxia in the RF and VM (p<0.05), and a similar trend in VL (p=0.10). At the same relative intensity, the RMS was greater in normoxia than in hypoxia in RF, VL, and BF (p<0.05), with a similar trend in VM (p=0.08). Median frequency increased with exercise intensity (p<0.05), and was higher in hypoxia than in normoxia in VL (p<0.05). Muscle contraction burst duration increased with exercise intensity in VM and VL (p<0.05), without clear effects of FIO2. No significant FIO2 effects on frequency domain indices were observed when compared at the same relative intensity. In conclusion, muscle activation during whole body exercise increases almost linearly with exercise intensity, following a muscle-specific pattern, which is adjusted depending on the FIO2 and the relative intensity of exercise. Both VL and VM are increasingly involved in power output generation with the increase of intensity and the reduction in FIO2. PMID:25225839

  3. Exposure to acute severe hypoxia leads to increased urea loss and disruptions in acid-base and ionoregulatory balance in dogfish sharks (Squalus acanthias).

    PubMed

    Zimmer, Alex M; Wood, Chris M

    2014-01-01

    The effects of acute moderate (20% air O2 saturation; 6-h exposure) and severe (5% air O2 saturation; 4-h exposure) hypoxia on N-waste, acid-base, and ion balance in dogfish sharks (Squalus acanthias suckleyi) were evaluated. We predicted that the synthesis and/or retention of urea, which are active processes, would be inhibited by hypoxia. Exposure to moderate hypoxia had negligible effects on N-waste fluxes or systemic physiology, except for a modest rise in plasma lactate. Exposure to severe hypoxia led to a significant increase in urea excretion (Jurea), while plasma, liver, and muscle urea concentrations were unchanged, suggesting a loss of urea retention. Ammonia excretion (Jamm) was elevated during normoxic recovery. Moreover, severe hypoxia led to disruptions in acid-base balance, indicated by a large increase in plasma [lactate] and substantial decreases in arterial pHa and plasma [Formula: see text], as well as loss of ionic homeostasis, indicated by increases in plasma [Mg(2+)], [Ca(2+)], and [Na(+)]. We suggest that severe hypoxia in dogfish sharks leads to a reduction in active gill homeostatic processes, such as urea retention, acid-base regulation and ionoregulation, and/or an osmoregulatory compromise due to increased functional gill surface area. Overall, the results provide a comprehensive picture of the physiological responses to a severe degree of hypoxia in an ancient fish species. PMID:25244375

  4. Severe acute intermittent hypoxia elicits phrenic long-term facilitation by a novel adenosine-dependent mechanism

    PubMed Central

    Nichols, Nicole L.; Dale, Erica A.

    2012-01-01

    Acute intermittent hypoxia [AIH; 3, 5-min episodes; 35–45 mmHg arterial Po2 (PaO2)] elicits serotonin-dependent phrenic long-term facilitation (pLTF), a form of phrenic motor facilitation (pMF) initiated by Gq protein-coupled metabotropic 5-HT2 receptors. An alternate pathway to pMF is induced by Gs protein-coupled metabotropic receptors, including adenosine A2A receptors. AIH-induced pLTF is dominated by the serotonin-dependent pathway and is actually restrained via inhibition from the adenosine-dependent pathway. Here, we hypothesized that severe AIH shifts pLTF from a serotonin-dependent to an adenosine-dependent form of pMF. pLTF induced by severe (25–30 mmHg PaO2) and moderate (45–55 mmHg PaO2) AIH were compared in anesthetized rats, with and without intrathecal (C4) spinal A2A (MSX-3, 130 ng/kg, 12 μl) or 5-HT receptor antagonist (methysergide, 300 μg/kg, 15 μl) injections. During severe, but not moderate AIH, progressive augmentation of the phrenic response during hypoxic episodes was observed. Severe AIH (78% ± 8% 90 min post-AIH, n = 6) elicited greater pLTF vs. moderate AIH (41% ± 12%, n = 8; P < 0.05). MSX-3 (28% ± 6%; n = 6; P < 0.05) attenuated pLTF following severe AIH, but enhanced pLTF following moderate AIH (86% ± 26%; n = 8; P < 0.05). Methysergide abolished pLTF after moderate AIH (12% ± 5%; n = 6; P = 0.035), but had no effect after severe AIH (66 ± 13%; n = 5; P > 0.05). Thus severe AIH shifts pLTF from a serotonin-dependent to an adenosine-dependent mechanism; the adenosinergic pathway inhibits the serotonergic pathway following moderate AIH. Here we demonstrate a novel adenosine-dependent pathway to pLTF following severe AIH. Shifts in the mechanisms of respiratory plasticity provide the ventilatory control system greater flexibility as challenges that differ in severity are confronted. PMID:22403346

  5. Sympathoadrenal responses to acute and chronic hypoxia in the rat.

    PubMed Central

    Johnson, T S; Young, J B; Landsberg, L

    1983-01-01

    The sympathoadrenal responses to acute and chronic hypoxic exposure at 10.5 and 7.5% oxygen were determined in the rat. Cardiac norepinephrine (NE) turnover was used to assess sympathetic nervous system (SNS) activity, and urinary excretion of epinephrine (E) was measured as an index of adrenal medullary activity. The responses of the adrenal medulla and SNS were distinct and dependent upon the degree and duration of hypoxic exposure. Chronic hypoxia at 10.5% oxygen increased cardiac NE turnover by 130% after 3, 7, and 14 d of hypoxic exposure. Urinary excretion of NE was similarly increased over this time interval, while urinary E excretion was marginally elevated. In contrast, acute exposure to moderate hypoxia at 10.5% oxygen was not associated with an increase in SNS activity; in fact, decreased SNS activity was suggested by diminished cardiac NE turnover and urinary NE excretion over the first 12 h of hypoxic exposure, and by a rebound increase in NE turnover after reexposure to normal oxygen tension. Adrenal medullary activity, on the other hand, increased substantially during acute exposure to moderate hypoxia (2-fold increase in urinary E excretion) and severe hypoxia (greater than 10-fold). In distinction to the lack of effect of acute hypoxic exposure (10.5% oxygen), the SNS was markedly stimulated during the first day of hypoxia exposure at 7.5% oxygen, an increase that was sustained throughout at least 7 d at 7.5% oxygen. These results demonstrate that chronic exposure to moderate and severe hypoxia increases the activity of the SNS and adrenal medulla, the effect being greater in severe hypoxic exposure. The response to acute hypoxic exposure is more complicated; during the first 12 h of exposure at 10.5% oxygen, the SNS is not stimulated and appears to be restrained, while adrenal medullary activity is enhanced. Acute exposure to a more severe degree of hypoxia (7.5% oxygen), however, is associated with stimulation of both the SNS and adrenal medulla

  6. Increased hemoglobin O2 affinity protects during acute hypoxia.

    PubMed

    Yalcin, Ozlem; Cabrales, Pedro

    2012-08-01

    Acclimatization to hypoxia requires time to complete the adaptation mechanisms that influence oxygen (O(2)) transport and O(2) utilization. Although decreasing hemoglobin (Hb) O(2) affinity would favor the release of O(2) to the tissues, increasing Hb O(2) affinity would augment arterial O(2) saturation during hypoxia. This study was designed to test the hypothesis that pharmacologically increasing the Hb O(2) affinity will augment O(2) transport during severe hypoxia (10 and 5% inspired O(2)) compared with normal Hb O(2) affinity. RBC Hb O(2) affinity was increased by infusion of 20 mg/kg of 5-hydroxymethyl-2-furfural (5HMF). Control animals received only the vehicle. The effects of increasing Hb O(2) affinity were studied in the hamster window chamber model, in terms of systemic and microvascular hemodynamics and partial pressures of O(2) (Po(2)). Pimonidazole binding to hypoxic areas of mice heart and brain was also studied. 5HMF decreased the Po(2) at which the Hb is 50% saturated with O(2) by 12.6 mmHg. During 10 and 5% O(2) hypoxia, 5HMF increased arterial blood O(2) saturation by 35 and 48% from the vehicle group, respectively. During 5% O(2) hypoxia, blood pressure and heart rate were 58 and 30% higher for 5HMF compared with the vehicle. In addition, 5HMF preserved microvascular blood flow, whereas blood flow decreased to 40% of baseline in the vehicle group. Consequently, perivascular Po(2) was three times higher in the 5HMF group compared with the control group at 5% O(2) hypoxia. 5HMF also reduced heart and brain hypoxic areas in mice. Therefore, increased Hb O(2) affinity resulted in hemodynamics and oxygenation benefits during severe hypoxia. This acute acclimatization process may have implications in survival during severe environmental hypoxia when logistic constraints prevent chronic acclimatization. PMID:22636677

  7. Increased hemoglobin O2 affinity protects during acute hypoxia

    PubMed Central

    Yalcin, Ozlem

    2012-01-01

    Acclimatization to hypoxia requires time to complete the adaptation mechanisms that influence oxygen (O2) transport and O2 utilization. Although decreasing hemoglobin (Hb) O2 affinity would favor the release of O2 to the tissues, increasing Hb O2 affinity would augment arterial O2 saturation during hypoxia. This study was designed to test the hypothesis that pharmacologically increasing the Hb O2 affinity will augment O2 transport during severe hypoxia (10 and 5% inspired O2) compared with normal Hb O2 affinity. RBC Hb O2 affinity was increased by infusion of 20 mg/kg of 5-hydroxymethyl-2-furfural (5HMF). Control animals received only the vehicle. The effects of increasing Hb O2 affinity were studied in the hamster window chamber model, in terms of systemic and microvascular hemodynamics and partial pressures of O2 (Po2). Pimonidazole binding to hypoxic areas of mice heart and brain was also studied. 5HMF decreased the Po2 at which the Hb is 50% saturated with O2 by 12.6 mmHg. During 10 and 5% O2 hypoxia, 5HMF increased arterial blood O2 saturation by 35 and 48% from the vehicle group, respectively. During 5% O2 hypoxia, blood pressure and heart rate were 58 and 30% higher for 5HMF compared with the vehicle. In addition, 5HMF preserved microvascular blood flow, whereas blood flow decreased to 40% of baseline in the vehicle group. Consequently, perivascular Po2 was three times higher in the 5HMF group compared with the control group at 5% O2 hypoxia. 5HMF also reduced heart and brain hypoxic areas in mice. Therefore, increased Hb O2 affinity resulted in hemodynamics and oxygenation benefits during severe hypoxia. This acute acclimatization process may have implications in survival during severe environmental hypoxia when logistic constraints prevent chronic acclimatization. PMID:22636677

  8. Approximate Simulation of Acute Hypobaric Hypoxia with Normobaric Hypoxia

    NASA Technical Reports Server (NTRS)

    Conkin, J.; Wessel, J. H., III

    2011-01-01

    INTRODUCTION. Some manufacturers of reduced oxygen (O2) breathing devices claim a comparable hypobaric hypoxia (HH) training experience by providing F(sub I) O2 < 0.209 at or near sea level pressure to match the ambient O2 partial pressure (iso-pO2) of the target altitude. METHODS. Literature from investigators and manufacturers indicate that these devices may not properly account for the 47 mmHg of water vapor partial pressure that reduces the inspired partial pressure of O2 (P(sub I) O2). Nor do they account for the complex reality of alveolar gas composition as defined by the Alveolar Gas Equation. In essence, by providing iso-pO2 conditions for normobaric hypoxia (NH) as for HH exposures the devices ignore P(sub A)O2 and P(sub A)CO2 as more direct agents to induce signs and symptoms of hypoxia during acute training exposures. RESULTS. There is not a sufficient integrated physiological understanding of the determinants of P(sub A)O2 and P(sub A)CO2 under acute NH and HH given the same hypoxic pO2 to claim a device that provides isohypoxia. Isohypoxia is defined as the same distribution of hypoxia signs and symptoms under any circumstances of equivalent hypoxic dose, and hypoxic pO2 is an incomplete hypoxic dose. Some devices that claim an equivalent HH experience under NH conditions significantly overestimate the HH condition, especially when simulating altitudes above 10,000 feet (3,048 m). CONCLUSIONS. At best, the claim should be that the devices provide an approximate HH experience since they only duplicate the ambient pO2 at sea level as at altitude (iso-pO2 machines). An approach to reduce the overestimation is to at least provide machines that create the same P(sub I)O2 (iso-P(sub I)O2 machines) conditions at sea level as at the target altitude, a simple software upgrade.

  9. Impact of Transient Acute Hypoxia on the Developing Mouse EEG

    PubMed Central

    Zanelli, S.; Goodkin, H.P.; Kowalski, S.; Kapur, J.

    2015-01-01

    Hypoxemic events are common in sick preterm and term infants and represent the most common cause of seizures in the newborn period. Neonatal seizures often lack clinical correlates and are only recognized by electroencephalogram (EEG). The mechanisms leading from a hypoxic/ischemic insult to acute seizures in neonates remain poorly understood. Further, the effects of hypoxia on EEG at various developmental stages have not been fully characterized in neonatal animals, in part due to technical challenges. We evaluated the impact of hypoxia on neonatal mouse EEG to define periods of increased susceptibility to seizures during postnatal development. Hippocampal and cortical electrodes were implanted stereotaxically in C57BL/6 mice from postnatal age 3 (P3) to P15. Following recovery, EEG recording were obtained during baseline, acute hypoxia (4% FiO2 for 4 min) and reoxygenation. In baseline recordings, maturation of EEG was characterized by the appearance of a more continuous background pattern that replaced alternating high and low amplitude activity. Clinical seizures during hypoxia were observed more frequently in younger animals (100% P3-4, 87.5% P5-6, 93% P7-8, 83% P9-10, 33% P11-12, 17% P15, r2=0.81) and also occurred at higher FiO2 in younger animals (11.2±1.1% P3-P6 vs. 8.9±0.8% P7-12, p<0.05). Background attenuation followed the initial hypoxemic seizure; progressive return to baseline during reoxygenation was observed in survivors. Electrographic seizures without clinical manifestations were observed during reoxygenation, again more commonly in younger animals (83% P3-4, 86% P5-6, 75% P7-8, 71% P9-10, 20% P11-12, r2=0.82). All P15 animals died with this duration and degree of hypoxia. Post-ictal abnormalities included burst attenuation and post-anoxic myoclonus and were more commonly seen in older animals. In summary, neonatal mice exposed to brief and severe hypoxia followed by rapid reoxygenation reliably develop seizures and the response to hypoxia

  10. Acute mountain sickness: medical problems associated with acute and subacute exposure to hypobaric hypoxia.

    PubMed

    Clarke, C

    2006-11-01

    This article summarises the medical problems of travel to altitudes above 3000 m. These are caused by chronic hypoxia. Acute mountain sickness (AMS), a self limiting common illness is almost part of normal acclimatisation--a transient condition lasting for several days. However, in <2% of people staying above 4000 m, serious illnesses related to hypoxia develop--high altitude pulmonary oedema and cerebral oedema. These are potentially fatal but can be largely avoided by gradual ascent. Short vacations, pressure from travel companies and peer groups often encourage ascent to 4000 m more rapidly than is prudent. Sensible guidelines for ascent are outlined, clinical features, management and treatment of these conditions. PMID:17099095

  11. Melatonin modulates the fetal cardiovascular defense response to acute hypoxia.

    PubMed

    Thakor, Avnesh S; Allison, Beth J; Niu, Youguo; Botting, Kimberley J; Serón-Ferré, Maria; Herrera, Emilio A; Giussani, Dino A

    2015-08-01

    Experimental studies in animal models supporting protective effects on the fetus of melatonin in adverse pregnancy have prompted clinical trials in human pregnancy complicated by fetal growth restriction. However, the effects of melatonin on the fetal defense to acute hypoxia, such as that which may occur during labor, remain unknown. This translational study tested the hypothesis, in vivo, that melatonin modulates the fetal cardiometabolic defense responses to acute hypoxia in chronically instrumented late gestation fetal sheep via alterations in fetal nitric oxide (NO) bioavailability. Under anesthesia, 6 fetal sheep at 0.85 gestation were instrumented with vascular catheters and a Transonic flow probe around a femoral artery. Five days later, fetuses were exposed to acute hypoxia with or without melatonin treatment. Fetal blood was taken to determine blood gas and metabolic status and plasma catecholamine concentrations. Hypoxia during melatonin treatment was repeated during in vivo NO blockade with the NO clamp. This technique permits blockade of de novo synthesis of NO while compensating for the tonic production of the gas, thereby maintaining basal cardiovascular function. Melatonin suppressed the redistribution of blood flow away from peripheral circulations and the glycemic and plasma catecholamine responses to acute hypoxia. These are important components of the fetal brain sparing response to acute hypoxia. The effects of melatonin involved NO-dependent mechanisms as the responses were reverted by fetal treatment with the NO clamp. Melatonin modulates the in vivo fetal cardiometabolic responses to acute hypoxia by increasing NO bioavailability. PMID:25908097

  12. Melatonin modulates the fetal cardiovascular defense response to acute hypoxia

    PubMed Central

    Thakor, Avnesh S; Allison, Beth J; Niu, Youguo; Botting, Kimberley J; Serón-Ferré, Maria; Herrera, Emilio A; Giussani, Dino A

    2015-01-01

    Experimental studies in animal models supporting protective effects on the fetus of melatonin in adverse pregnancy have prompted clinical trials in human pregnancy complicated by fetal growth restriction. However, the effects of melatonin on the fetal defense to acute hypoxia, such as that which may occur during labor, remain unknown. This translational study tested the hypothesis, in vivo, that melatonin modulates the fetal cardiometabolic defense responses to acute hypoxia in chronically instrumented late gestation fetal sheep via alterations in fetal nitric oxide (NO) bioavailability. Under anesthesia, 6 fetal sheep at 0.85 gestation were instrumented with vascular catheters and a Transonic flow probe around a femoral artery. Five days later, fetuses were exposed to acute hypoxia with or without melatonin treatment. Fetal blood was taken to determine blood gas and metabolic status and plasma catecholamine concentrations. Hypoxia during melatonin treatment was repeated during in vivo NO blockade with the NO clamp. This technique permits blockade of de novo synthesis of NO while compensating for the tonic production of the gas, thereby maintaining basal cardiovascular function. Melatonin suppressed the redistribution of blood flow away from peripheral circulations and the glycemic and plasma catecholamine responses to acute hypoxia. These are important components of the fetal brain sparing response to acute hypoxia. The effects of melatonin involved NO-dependent mechanisms as the responses were reverted by fetal treatment with the NO clamp. Melatonin modulates the in vivo fetal cardiometabolic responses to acute hypoxia by increasing NO bioavailability. PMID:25908097

  13. Arterial to end-tidal Pco2 difference during exercise in normoxia and severe acute hypoxia: importance of blood temperature correction

    PubMed Central

    Losa-Reyna, José; Torres-Peralta, Rafael; Henriquez, Juan José González; Calbet, José A L

    2015-01-01

    Negative arterial to end-tidal Pco2 differences ((a-ET)Pco2) have been reported in normoxia. To determine the influence of blood temperature on (a-ET)Pco2, 11 volunteers (21 ± 2 years) performed incremental exercise to exhaustion in normoxia (Nx, PIo2: 143 mmHg) and hypoxia (Hyp, PIo2: 73 mmHg), while arterial blood gases and temperature (ABT) were simultaneously measured together with end-tidal Pco2 (PETco2). After accounting for blood temperature, the (a-ET) Pco2 was reduced (in absolute values) from −4.2 ± 1.6 to −1.1 ± 1.5 mmHg in normoxia and from −1.7 ± 1.6 to 0.9 ± 0.9 mmHg in hypoxia (both P < 0.05). The temperature corrected (a-ET)Pco2 was linearly related with absolute and relative exercise intensity, VO2, VCO2, and respiratory rate (RR) in normoxia and hypoxia (R2: 0.52–0.59). Exercise CO2 production and PETco2 values were lower in hypoxia than normoxia, likely explaining the greater (less negative) (a-ET)Pco2 difference in hypoxia than normoxia (P < 0.05). At near-maximal exercise intensity the (a-ET)Pco2 lies close to 0 mmHg, that is, the mean Paco2 and the mean PETco2 are similar. The mean exercise (a-ET)Pco2 difference is closely related to the mean A-aDO2 difference (r = 0.90, P < 0.001), as would be expected if similar mechanisms perturb the gas exchange of O2 and CO2 during exercise. In summary, most of the negative (a-ET)Pco2 values observed in previous studies are due to lack of correction of Paco2 for blood temperature. The absolute magnitude of the (a-ET)Pco2 difference is lower during exercise in hypoxia than normoxia. PMID:26508736

  14. Severe nocturnal and postexercise hypoxia in children and adolescents with sickle cell disease.

    PubMed

    Halphen, Isabelle; Elie, Caroline; Brousse, Valentine; Le Bourgeois, Muriel; Allali, Slimane; Bonnet, Damien; de Montalembert, Mariane

    2014-01-01

    Hypoxia is a common feature in children with sickle cell disease (SCD) that is inconsistently associated with painful crises and acute chest syndrome. To assess the prevalence and risk factors of hypoxia, we recorded daytime, nocturnal, and postexercise pulse oximetry (SpO2) values in 39 SCD patients with a median age of 10.8 years. Median daytime SpO2 was 97% (range, 89%-100%), and 36% of patients had daytime hypoxia defined as SpO2<96%. Median nocturnal SpO2 was 94.7% (range, 87.7%-99.5%), 50% of patients had nocturnal hypoxia defined as SpO2≤93%, and 11(37%) patients spent more than 10% of their total sleep time with SpO2<90%. Median postexercise SpO2 was 94% (range, 72%-100%) and 44.7% of patients had postexercise hypoxia defined as an SpO2 decrease ≥3% after a 6-minute walk test. Among patients with normal daytime SpO2, 35% had nocturnal and 42% postexercise hypoxia. Compared to 9 patients without daytime, nocturnal, or postexercise hypoxia, 25 patients with hypoxia under at least one of these three conditions had greater anemia severity (P = 0.01), lower HbF levels (P = 0.04), and higher aspartate aminotransferase levels (P = 0.03). Males predominated among patients with postexercise hypoxia (P = 0.004). Hypoxia correlated neither with painful crises nor with acute chest syndrome. Of 32 evaluable patients, 6 (18.8%) had a tricuspid regurgitation velocity ≥2.6 m/s, and this feature was associated with anemia (P = 0.044). Median percentage of the predicted distance covered during a 6-minute walk test was 86% [46-120]; the distance was negatively associated with LDH (P = 0.044) and with a past history of acute chest syndrome (P = 0.009). In conclusion, severe episodes of nocturnal and postexercise hypoxia are common in children with SCD, even those with normal daytime SpO2. PMID:24878576

  15. Cardiovascular and cerebrovascular responses to acute hypoxia following exposure to intermittent hypoxia in healthy humans

    PubMed Central

    Foster, Glen E; Brugniaux, Julien V; Pialoux, Vincent; Duggan, Cailean T C; Hanly, Patrick J; Ahmed, Sofia B; Poulin, Marc J

    2009-01-01

    Intermittent hypoxia (IH) is thought to be responsible for many of the long-term cardiovascular consequences associated with obstructive sleep apnoea (OSA). Experimental human models of IH can aid in investigating the pathophysiology of these cardiovascular complications. The purpose of this study was to determine the effects of IH on the cardiovascular and cerebrovascular response to acute hypoxia and hypercapnia in an experimental human model that simulates the hypoxaemia experienced by OSA patients. We exposed 10 healthy, male subjects to IH for 4 consecutive days. The IH profile involved 2 min of hypoxia (nadir = 45.0 mmHg) alternating with 2 min of normoxia (peak = 88.0 mmHg) for 6 h. The cerebral blood flow response and the pressor responses to hypoxia and hypercapnia were assessed after 2 days of sham exposure, after each day of IH, and 4 days following the discontinuation of IH. Nitric oxide derivatives were measured at baseline and following the last exposure to IH. After 4 days of IH, mean arterial pressure increased by 4 mmHg (P < 0.01), nitric oxide derivatives were reduced by 55% (P < 0.05), the pressor response to acute hypoxia increased (P < 0.01), and the cerebral vascular resistance response to hypoxia increased (P < 0.01). IH alters blood pressure and cerebrovascular regulation, which is likely to contribute to the pathogenesis of cardiovascular and cerebrovascular disease in patients with OSA. PMID:19417094

  16. Two long-lasting central respiratory responses following acute hypoxia in glomectomized cats.

    PubMed

    Gallman, E A; Millhorn, D E

    1988-01-01

    1. Central respiratory response to acute (10 min) hypoxia, as measured by phrenic nerve activity, was determined in peripheral chemo-denervated cats. 2. Hypoxia was induced by ventilating cats for 10 min at reduced inspired oxygen levels (inspired O2 fraction, FI,O2 = 0.06-0.15). The degree of hypoxaemia was determined from an arterial blood sample and ranged from 'severe' (arterial O2 pressure, Pa,O2 less than 26 Torr) to 'mild' (Pa,O2 greater than 35 Torr). The respiratory response was monitored for 1 h following return to ventilation with 100% oxygen. 3. The results confirmed the finding of prolonged (greater than 60 min) inhibition of respiration upon return to hyperoxic conditions following severe hypoxia, as reported previously (Millhorn, Eldridge, Kiley & Waldrop, 1984). A new finding was a long-lasting (greater than 60 min) facilitation of respiration following exposure to less severe (Pa,O2 greater than 35 Torr) hypoxia. 4. Medullary extracellular fluid pH was measured in six cats. Changes in pH could not explain either the prolonged inhibition following severe hypoxia or the long-lasting facilitation observed following mild hypoxia. 5. Ablation studies were performed in order to determine the locations of the neuronal substrates for the inhibitory and facilitatory mechanisms. The results of this series of experiments indicate that the mesencephalon is necessary for activation of the inhibitory mechanism, while the facilitatory mechanism requires the presence of higher brain structures, notably the diencephalon. 6. Following removal of the diencephalon, the inhibitory response was seen following even mild hypoxic insults, i.e. those shown to produce facilitation in animals with intact brains. In the absence of the mesencephalon, neither prolonged inhibition nor prolonged facilitation could be produced following hypoxia. 7. It is proposed that there are two centrally mediated long-lasting responses to acute hypoxia. Facilitation is seen following mild

  17. Acute and chronic hypoxia: implications for cerebral function and exercise tolerance

    PubMed Central

    Goodall, Stuart; Twomey, Rosie; Amann, Markus

    2015-01-01

    Purpose To outline how hypoxia profoundly affects neuronal functionality and thus compromise exercise-performance. Methods Investigations using electroencephalography (EEG) and transcranial magnetic stimulation (TMS) detecting neuronal changes at rest and those studying fatiguing effects on whole-body exercise performance in acute (AH) and chronic hypoxia (CH) were evaluated. Results At rest during very early hypoxia (<1-h), slowing of cerebral neuronal activity is evident despite no change in corticospinal excitability. As time in hypoxia progresses (3-h), increased corticospinal excitability becomes evident; however, changes in neuronal activity are unknown. Prolonged exposure (3–5 d) causes a respiratory alkalosis which modulates Na+ channels, potentially explaining reduced neuronal excitability. Locomotor exercise in AH exacerbates the development of peripheral-fatigue; as the severity of hypoxia increases, mechanisms of peripheral-fatigue become less dominant and CNS hypoxia becomes the predominant factor. The greatest central-fatigue in AH occurs when SaO2 is ≤75%, a level that coincides with increasing impairments in neuronal activity. CH does not improve the level of peripheral-fatigue observed in AH; however, it attenuates the development of central-fatigue paralleling increases in cerebral O2 availability and corticospinal excitability. Conclusions The attenuated development of central-fatigue in CH might explain, the improvements in locomotor exercise-performance commonly observed after acclimatisation to high altitude. PMID:25593787

  18. Effect of acute exposure to moderate altitude on muscle power: hypobaric hypoxia vs. normobaric hypoxia.

    PubMed

    Feriche, Belén; García-Ramos, Amador; Calderón-Soto, Carmen; Drobnic, Franchek; Bonitch-Góngora, Juan G; Galilea, Pedro A; Riera, Joan; Padial, Paulino

    2014-01-01

    When ascending to a higher altitude, changes in air density and oxygen levels affect the way in which explosive actions are executed. This study was designed to compare the effects of acute exposure to real or simulated moderate hypoxia on the dynamics of the force-velocity relationship observed in bench press exercise. Twenty-eight combat sports athletes were assigned to two groups and assessed on two separate occasions: G1 (n = 17) in conditions of normoxia (N1) and hypobaric hypoxia (HH) and G2 (n = 11) in conditions of normoxia (N2) and normobaric hypoxia (NH). Individual and complete force-velocity relationships in bench press were determined on each assessment day. For each exercise repetition, we obtained the mean and peak velocity and power shown by the athletes. Maximum power (Pmax) was recorded as the highest P(mean) obtained across the complete force-velocity curve. Our findings indicate a significantly higher absolute load linked to P(max) (∼ 3%) and maximal strength (1 RM) (∼ 6%) in G1 attributable to the climb to altitude (P<0.05). We also observed a stimulating effect of natural hypoxia on P(mean) and P(peak) in the middle-high part of the curve (≥ 60 kg; P<0.01) and a 7.8% mean increase in barbell displacement velocity (P<0.001). No changes in any of the variables examined were observed in G2. According to these data, we can state that acute exposure to natural moderate altitude as opposed to simulated normobaric hypoxia leads to gains in 1 RM, movement velocity and power during the execution of a force-velocity curve in bench press. PMID:25474104

  19. Effect of Acute Exposure to Moderate Altitude on Muscle Power: Hypobaric Hypoxia vs. Normobaric Hypoxia

    PubMed Central

    Feriche, Belén; García-Ramos, Amador; Calderón-Soto, Carmen; Drobnic, Franchek; Bonitch- Góngora, Juan G.; Galilea, Pedro A.; Riera, Joan; Padial, Paulino

    2014-01-01

    When ascending to a higher altitude, changes in air density and oxygen levels affect the way in which explosive actions are executed. This study was designed to compare the effects of acute exposure to real or simulated moderate hypoxia on the dynamics of the force-velocity relationship observed in bench press exercise. Twenty-eight combat sports athletes were assigned to two groups and assessed on two separate occasions: G1 (n = 17) in conditions of normoxia (N1) and hypobaric hypoxia (HH) and G2 (n = 11) in conditions of normoxia (N2) and normobaric hypoxia (NH). Individual and complete force-velocity relationships in bench press were determined on each assessment day. For each exercise repetition, we obtained the mean and peak velocity and power shown by the athletes. Maximum power (Pmax) was recorded as the highest Pmean obtained across the complete force-velocity curve. Our findings indicate a significantly higher absolute load linked to Pmax (∼3%) and maximal strength (1RM) (∼6%) in G1 attributable to the climb to altitude (P<0.05). We also observed a stimulating effect of natural hypoxia on Pmean and Ppeak in the middle-high part of the curve (≥60 kg; P<0.01) and a 7.8% mean increase in barbell displacement velocity (P<0.001). No changes in any of the variables examined were observed in G2. According to these data, we can state that acute exposure to natural moderate altitude as opposed to simulated normobaric hypoxia leads to gains in 1RM, movement velocity and power during the execution of a force-velocity curve in bench press. PMID:25474104

  20. The effects of acute intermittent hypoxia on cardiovascular parameters in normotensive and chronic hypobaric hypoxia-induced hypertensive rabbits.

    PubMed

    Yaman, Muhittin O; Guner, Ibrahim; Uzun, Hafize; Sahin, Gulderen; Yelmen, Nermin

    2014-01-01

    The effects of both chronic hypoxia and acute intermittent hypoxia (AIH) on cardiovascular system are unclear. We designed this study to develop a rabbit model of hypertension by exposure to chronic hypobaric hypoxia (CHH) and to investigate the effects of AIH on hypertensive rabbits. Present study was performed in 13 albino rabbits that divided into CHH and control groups. To develop hypertension, the rabbits were placed in a hypobaric chamber (390 mmHg; 22 hours/day, 30 days). Afterwards, AIH protocol was applied (8% FIO2 (Fraction of Inspired Oxygen) 1 min + 5 min normoxia, 20 cycles, 2 hours) to rabbits anesthetized with urethane and alpha-chloralose. Mean arterial pressure (MAP), heart rate (HR) and hematocrit values have been determined. Also asymmetric dimethylarginine (ADMA), endothelial nitric oxide synthase (eNOS), endothelin-1 and norepinephrine values have been analyzed in blood. We developed a model of hypertension in rabbits via exposure to severe CHH and we believe that ADMA is an important parameter in the development and permanence of CHH-induced hypertension. The main finding of this sudy was the depressor effect of AIH on blood pressure and heart rate in CHH- induced hypertension model. Finally, we believe that AIH protocol may be applicable for prevention and treatment of hypertension if properly developed. PMID:24448370

  1. Chronic intermittent hypoxia alters ventilatory and metabolic responses to acute hypoxia in rats.

    PubMed

    Morgan, Barbara J; Adrian, Russell; Wang, Zun-Yi; Bates, Melissa L; Dopp, John M

    2016-05-15

    We determined the effects of chronic exposure to intermittent hypoxia (CIH) on chemoreflex control of ventilation in conscious animals. Adult male Sprague-Dawley rats were exposed to CIH [nadir oxygen saturation (SpO2), 75%; 15 events/h; 10 h/day] or normoxia (NORM) for 21 days. We assessed the following responses to acute, graded hypoxia before and after exposures: ventilation (V̇e, via barometric plethysmography), V̇o2 and V̇co2 (analysis of expired air), heart rate (HR), and SpO2 (pulse oximetry via neck collar). We quantified hypoxia-induced chemoreceptor sensitivity by calculating the stimulus-response relationship between SpO2 and the ventilatory equivalent for V̇co2 (linear regression). An additional aim was to determine whether CIH causes proliferation of carotid body glomus cells (using bromodeoxyuridine). CIH exposure increased the slope of the V̇e/V̇co2/SpO2 relationship and caused hyperventilation in normoxia. Bromodeoxyuridine staining was comparable in CIH and NORM. Thus our CIH paradigm augmented hypoxic chemosensitivity without causing glomus cell proliferation. PMID:26917692

  2. Management of severe acute pancreatitis.

    PubMed

    Doctor, Nilesh; Agarwal, Pravin; Gandhi, Vidhyachandra

    2012-02-01

    Severe acute pancreatitis (SAP) develops in about 25% of patients with acute pancreatitis. Severity of acute pancreatitis is linked to the presence of systemic organ dysfunctions and/or necrotizing pancreatitis. Risk factors independently determining the outcome of SAP are early multiorgan failure (MOF), infection of necrosis, and extended necrosis (>50%). Morbidity of SAP is biphasic, in the first week it is strongly related to systemic inflammatory response syndrome while, sepsis due to infected pancreatic necrosis leading to MOF syndrome occurs in the later course after the first week. Contrast-enhanced computed tomography provides the highest diagnostic accuracy for necrotizing pancreatitis when performed after the first week of disease. Patients who suffer early organ dysfunctions or are at risk for developing a severe disease require early intensive care treatment. Antibiotic prophylaxis has not been shown as an effective preventive treatment. Early enteral feeding is based on a high level of evidence, resulting in a reduction of local and systemic infection. Patients suffering infected necrosis causing clinical sepsis are candidates for intervention. Hospital mortality of SAP after interventional or surgical debridement has decreased to below 20% in high-volume centers. PMID:23372306

  3. Neutrophil gelatinase-associated lipocalin: its response to hypoxia and association with acute mountain sickness.

    PubMed

    Mellor, Adrian; Boos, Christopher; Stacey, Mike; Hooper, Tim; Smith, Chris; Begley, Joe; Yarker, Jo; Piper, Rick; O'Hara, John; King, Rod; Turner, Steve; Woods, David R

    2013-01-01

    Acute Mountain Sickness (AMS) is a common clinical challenge at high altitude (HA). A point-of-care biochemical marker for AMS could have widespread utility. Neutrophil gelatinase-associated lipocalin (NGAL) rises in response to renal injury, inflammation and oxidative stress. We investigated whether NGAL rises with HA and if this rise was related to AMS, hypoxia or exercise. NGAL was assayed in a cohort (n = 22) undertaking 6 hours exercise at near sea-level (SL); a cohort (n = 14) during 3 hours of normobaric hypoxia (FiO2 11.6%) and on two trekking expeditions (n = 52) to over 5000 m. NGAL did not change with exercise at SL or following normobaric hypoxia. During the trekking expeditions NGAL levels (ng/ml, mean ± sd, range) rose significantly (P < 0.001) from 68 ± 14 (60-102) at 1300 m to 183 ± 107 (65-519); 143 ± 66 (60-315) and 150 ± 71 (60-357) at 3400 m, 4270 m and 5150 m respectively. At 5150 m there was a significant difference in NGAL between those with severe AMS (n = 7), mild AMS (n = 16) or no AMS (n = 23): 201 ± 34 versus 171 ± 19 versus 124 ± 12 respectively (P = 0.009 for severe versus no AMS; P = 0.026 for mild versus no AMS). In summary, NGAL rises in response to prolonged hypobaric hypoxia and demonstrates a relationship to the presence and severity of AMS. PMID:24227892

  4. Modulation of the sympathetic response to acute hypoxia by the caudal ventrolateral medulla in rats

    PubMed Central

    Mandel, Daniel A; Schreihofer, Ann M

    2009-01-01

    Hypoxia elevates splanchnic sympathetic nerve activity (SNA) with differential effects during inspiration and expiration by unresolved central mechanisms. We examined the hypothesis that cardiovascular-related neurones in the caudal ventrolateral medulla (CVLM) contribute to the complex sympathetic response to hypoxia. In chloralose-anaesthetized, ventilated, vagotomized rats, acute hypoxia (10% O2, 60 s) evoked an increase in SNA (103 ± 12%) that was characterized by a decrease in activity during early inspiration followed by a prominent rise during expiration. Some recorded baro-activated CVLM neurones (n= 13) were activated by hypoxia, and most of these neurones displayed peak activity during inspiration that was enhanced during hypoxia. In contrast, other baro-activated CVLM neurones were inhibited during hypoxia (n= 6), and most of these neurones showed peak activity during expiration prior to the onset of hypoxia. Microinjection of the glutamate antagonist kynurenate into the CVLM eliminated the respiratory-related fluctuations in SNA during hypoxia and exaggerated the magnitude of the sympathetic response. In contrast, microinjection of a GABAA antagonist (bicuculline or gabazine) into the CVLM dramatically attenuated the sympathetic response to hypoxia. These data suggest the response to hypoxia in baro-activated CVLM neurones is related to their basal pattern of respiratory-related activity, and changes in the activity of these neurones is consistent with a contribution to the respiratory-related sympathetic responses to hypoxia. Furthermore, both glutamate and GABA in the CVLM contribute to the complex sympathetic response to acute hypoxia. PMID:19047207

  5. Acute physical exercise under hypoxia improves sleep, mood and reaction time.

    PubMed

    de Aquino-Lemos, Valdir; Santos, Ronaldo Vagner T; Antunes, Hanna Karen Moreira; Lira, Fabio S; Luz Bittar, Irene G; Caris, Aline V; Tufik, Sergio; de Mello, Marco Tulio

    2016-02-01

    This study aimed to assess the effect of two sessions of acute physical exercise at 50% VO2peak performed under hypoxia (equivalent to an altitude of 4500 m for 28 h) on sleep, mood and reaction time. Forty healthy men were randomized into 4 groups: Normoxia (NG) (n = 10); Hypoxia (HG) (n = 10); Exercise under Normoxia (ENG) (n = 10); and Exercise under Hypoxia (EHG) (n = 10). All mood and reaction time assessments were performed 40 min after awakening. Sleep was reassessed on the first day at 14 h after the initiation of hypoxia; mood and reaction time were measured 28 h later. Two sessions of acute physical exercise at 50% VO2peak were performed for 60 min on the first and second days after 3 and 27 h, respectively, after starting to hypoxia. Improved sleep efficiency, stage N3 and REM sleep and reduced wake after sleep onset were observed under hypoxia after acute physical exercise. Tension, anger, depressed mood, vigor and reaction time scores improved after exercise under hypoxia. We conclude that hypoxia impairs sleep, reaction time and mood. Acute physical exercise at 50% VO2peak under hypoxia improves sleep efficiency, reversing the aspects that had been adversely affected under hypoxia, possibly contributing to improved mood and reaction time. PMID:26522742

  6. Microenvironmental oxygen partial pressure in acute myeloid leukemia: Is there really a role for hypoxia?

    PubMed

    Rieger, Christina T; Fiegl, Michael

    2016-07-01

    Reduced oxygen partial pressure (pO2) has been recognized as being relevant in hematopoiesis and the pathophysiology of malignant diseases. Although hypoxic (meaning insufficient supply of oxygen) and anoxic areas are present and of pathophysiologic importance (by hypoxia-induced pathways such as HiF1α) in solid tumors, this may not be true for (malignant) hematologic cells. Hematopoiesis occurs in the stem cell niche, which is characterized, among other things, by extremely low pO2. However, in contrast to solid tumors, in this context, the low pO2 is physiological and this feature, among others, is shared by the malignant stem cell niche harboring leukemia-initiating cells. Upon differentiation, hematopoietic cells are constantly exposed to changes in pO2 as they travel throughout the human body and encounter arterial and venous blood and migrate into oxygen-carrier-free tissue with low pO2. Hematologic malignancies such as acute myeloid leukemia (AML) make little difference in this respect and, whereas low oxygen is the usual environment of AML cells, recent evidence suggests no role for real hypoxia. Although there is no evidence that AML pathophysiology is related to hypoxia, leukemic blasts still show several distinct biological features when exposed to reduced pO2: they down- or upregulate membrane receptors such as CXCR4 or FLT3, activate or inhibit intracellular signaling pathways such as PI3K, and specifically secrete cytokines (IL-8). In summary, reduced pO2 should not be mistaken for hypoxia (nor should it be so called), and it does not automatically induce hypoxia-response mechanisms; therefore, a strict distinction should be made between physiologically low pO2 (physoxia) and hypoxia. PMID:27118044

  7. Severe acute malnutrition and infection

    PubMed Central

    Jones, Kelsey D J; Berkley, James A

    2014-01-01

    Severe acute malnutrition (SAM) is associated with increased severity of common infectious diseases, and death amongst children with SAM is almost always as a result of infection. The diagnosis and management of infection are often different in malnourished versus well-nourished children. The objectives of this brief are to outline the evidence underpinning important practical questions relating to the management of infectious diseases in children with SAM and to highlight research gaps. Overall, the evidence base for many aspects covered in this brief is very poor. The brief addresses antimicrobials; antipyretics; tuberculosis; HIV; malaria; pneumonia; diarrhoea; sepsis; measles; urinary tract infection; nosocomial Infections; soil transmitted helminths; skin infections and pharmacology in the context of SAM. The brief is structured into sets of clinical questions, which we hope will maximise the relevance to contemporary practice. PMID:25475887

  8. Severe Acute Pancreatitis in Pregnancy

    PubMed Central

    Abdullah, Bahiyah; Kathiresan Pillai, Thanikasalam; Cheen, Lim Huay; Ryan, Ray Joshua

    2015-01-01

    This is a case of a pregnant lady at 8 weeks of gestation, who presented with acute abdomen. She was initially diagnosed with ruptured ectopic pregnancy and ruptured corpus luteal cyst as the differential diagnosis. However she then, was finally diagnosed as acute hemorrhagic pancreatitis with spontaneous complete miscarriage. This is followed by review of literature on this topic. Acute pancreatitis in pregnancy is not uncommon. The emphasis on high index of suspicion of acute pancreatitis in women who presented with acute abdomen in pregnancy is highlighted. Early diagnosis and good supportive care by multidisciplinary team are crucial to ensure good maternal and fetal outcomes. PMID:25628906

  9. [Electrical properties of limb muscular tissue in acute circulatory hypoxia].

    PubMed

    Kolchev, A I; Nasonkin, O S

    1994-01-01

    The study was undertaken to examine dispersion of the complex electric resistance and capacitive impedance of limb muscular tissue in the frequency range of 1 to 100 kHz in acute circulatory hypoxia caused by blood exfusion from the common carotid artery at 10-50% of the circulatory blood volume (CBV) at the same time local blood flow and oxygen tension in muscles were measured. Blood loss of 10-30% of CBV resulted in increased muscular tissue electric conductivity. Decompensated blood loss was characterized by a steady growth of complex electric resistance and capacitive impedance. There were the greatest changes in electric conductivity in the frequency range of 1-10 kHz. PMID:7824348

  10. Abundance of plasma antioxidant proteins confers tolerance to acute hypobaric hypoxia exposure.

    PubMed

    Padhy, Gayatri; Sethy, Niroj Kumar; Ganju, Lilly; Bhargava, Kalpana

    2013-09-01

    Systematic identification of molecular signatures for hypobaric hypoxia can aid in better understanding of human adaptation to high altitude. In an attempt to identify proteins promoting hypoxia tolerance during acute exposure to high altitude, we screened and identified hypoxia tolerant and susceptible rats based on hyperventilation time to a simulated altitude of 32,000 ft (9754 m). The hypoxia tolerance was further validated by estimating 8-isoprotane levels and protein carbonyls, which revealed that hypoxia tolerant rats possessed significant lower plasma levels as compared to susceptible rats. We used a comparative plasma proteome profiling approach using 2-dimensional gel electrophoresis (2-DGE) combined with MALDI TOF/TOF for both groups, along with an hypoxic control group. This resulted in the identification of 19 differentially expressed proteins. Seven proteins (TTR, GPx-3, PON1, Rab-3D, CLC11, CRP, and Hp) were upregulated in hypoxia tolerant rats, while apolipoprotein A-I (APOA1) was upregulated in hypoxia susceptible rats. We further confirmed the consistent higher expression levels of three antioxidant proteins (PON1, TTR, and GPx-3) in hypoxia-tolerant animals using ELISA and immunoblotting. Collectively, these proteomics-based results highlight the role of antioxidant enzymes in conferring hypoxia tolerance during acute hypobaric hypoxia. The expression of these antioxidant enzymes could be used as putative biomarkers for screening altitude adaptation as well as aiding in better management of altered oxygen pathophysiologies. PMID:24067188

  11. Acetazolamide during acute hypoxia improves tissue oxygenation in the human brain.

    PubMed

    Wang, Kang; Smith, Zachary M; Buxton, Richard B; Swenson, Erik R; Dubowitz, David J

    2015-12-15

    Low doses of the carbonic anhydrase inhibitor acetazolamide provides accelerated acclimatization to high-altitude hypoxia and prevention of cerebral and other symptoms of acute mountain sickness. We previously observed increases in cerebral O2 metabolism (CMRO2 ) during hypoxia. In this study, we investigate whether low-dose oral acetazolamide (250 mg) reduces this elevated CMRO2 and in turn might improve cerebral tissue oxygenation (PtiO2 ) during acute hypoxia. Six normal human subjects were exposed to 6 h of normobaric hypoxia with and without acetazolamide prophylaxis. We determined CMRO2 and cerebral PtiO2 from MRI measurements of cerebral blood flow (CBF) and cerebral venous O2 saturation. During normoxia, low-dose acetazolamide resulted in no significant change in CBF, CMRO2 , or PtiO2 . During hypoxia, we observed increases in CBF [48.5 (SD 12.4) (normoxia) to 65.5 (20.4) ml·100 ml(-1)·min(-1) (hypoxia), P < 0.05] and CMRO2 [1.54 (0.19) to 1.79 (0.25) μmol·ml(-1)·min(-1), P < 0.05] and a dramatic decline in PtiO2 [25.0 to 11.4 (2.7) mmHg, P < 0.05]. Acetazolamide prophylaxis mitigated these rises in CBF [53.7 (20.7) ml·100 ml(-1)·min(-1) (hypoxia + acetazolamide)] and CMRO2 [1.41 (0.09) μmol·ml(-1)·min(-1) (hypoxia + acetazolamide)] associated with acute hypoxia but also reduced O2 delivery [6.92 (1.45) (hypoxia) to 5.60 (1.14) mmol/min (hypoxia + acetazolamide), P < 0.05]. The net effect was improved cerebral tissue PtiO2 during acute hypoxia [11.4 (2.7) (hypoxia) to 16.5 (3.0) mmHg (hypoxia + acetazolamide), P < 0.05]. In addition to its renal effect, low-dose acetazolamide is effective at the capillary endothelium, and we hypothesize that local interruption in cerebral CO2 excretion accounts for the improvements in CMRO2 and ultimately in cerebral tissue oxygenation during hypoxia. This study suggests a potentially pivotal role of cerebral CO2 and pH in modulating CMRO2 and PtiO2 during acute hypoxia. PMID:26472861

  12. [Severe acute respiratory syndrome (SARS)].

    PubMed

    Gillissen, Adrian; Ruf, Bernhard R

    2003-06-15

    Severe acute respiratory syndrome (SARS) is a viral disease, observed primarily in Southern China in November 2002, with variable flu-like symptoms and pneumonia, in approx. 5% leading to death from respiratory distress syndrome (RDS). The disease was spread over more than 30 states all over the globe by SARS-virus-infected travelers. WHO and CDC received first information about a new syndrome by the end of February 2003, after the first cases outside the Republic of China had been observed. A case in Hanoi, Vietnam, led to the first precise information about the new disease entity to WHO, by Dr. Carlo Urbani, a co-worker of WHO/Doctors without Borders, who had been called by local colleagues to assist in the management of a patient with an unknown severe disease by the end of February 2003. Dr. Urbani died from SARS, as did many other health care workers. In the meantime, more than 7,000 cases have been observed worldwide, predominantly in China and Hong Kong, but also in Taiwan, Canada, Singapore, and the USA, and many other countries, and more than 600 of these patients died from RDS. Since the beginning of March 2003, when WHO and CDC started their activities, in close collaboration with a group of international experts, including the Bernhard-Nocht-Institute in Hamburg and the Department of Virology in Frankfurt/Main, a previously impossible success in the disclosure of the disease was achieved. Within only 8 weeks of research it was possible to describe the infectious agent, a genetically modified coronavirus, including the genetic sequence, to establish specific diagnostic PCR methods and to find possible mechanisms for promising therapeutic approaches. In addition, intensifying classical quarantine and hospital hygiene measures, it was possible to limit SARS in many countries to sporadic cases, and to reduce the disease in countries such as Canada and Vietnam. This review article summarizes important information about many issues of SARS (May 15th, 2003

  13. Neutrophil Gelatinase-Associated Lipocalin: Its Response to Hypoxia and Association with Acute Mountain Sickness

    PubMed Central

    Boos, Christopher; Stacey, Mike; Hooper, Tim; Smith, Chris; Yarker, Jo; Piper, Rick; O'Hara, John; King, Rod; Turner, Steve; Woods, David R.

    2013-01-01

    Acute Mountain Sickness (AMS) is a common clinical challenge at high altitude (HA). A point-of-care biochemical marker for AMS could have widespread utility. Neutrophil gelatinase-associated lipocalin (NGAL) rises in response to renal injury, inflammation and oxidative stress. We investigated whether NGAL rises with HA and if this rise was related to AMS, hypoxia or exercise. NGAL was assayed in a cohort (n = 22) undertaking 6 hours exercise at near sea-level (SL); a cohort (n = 14) during 3 hours of normobaric hypoxia (FiO2 11.6%) and on two trekking expeditions (n = 52) to over 5000 m. NGAL did not change with exercise at SL or following normobaric hypoxia. During the trekking expeditions NGAL levels (ng/ml, mean ± sd, range) rose significantly (P < 0.001) from 68 ± 14 (60–102) at 1300 m to 183 ± 107 (65–519); 143 ± 66 (60–315) and 150 ± 71 (60–357) at 3400 m, 4270 m and 5150 m respectively. At 5150 m there was a significant difference in NGAL between those with severe AMS (n = 7), mild AMS (n = 16) or no AMS (n = 23): 201 ± 34 versus 171 ± 19 versus 124 ± 12 respectively (P = 0.009 for severe versus no AMS; P = 0.026 for mild versus no AMS). In summary, NGAL rises in response to prolonged hypobaric hypoxia and demonstrates a relationship to the presence and severity of AMS. PMID:24227892

  14. Intermittent severe hypoxia induces plasticity within serotonergic and catecholaminergic neurons in the neonatal rat ventrolateral medulla.

    PubMed

    Givan, Scott A; Cummings, Kevin J

    2016-06-01

    5-HT neurons contribute to autoresuscitation and survival during intermittent severe hypoxia (IsH). In adults, catecholaminergic neurons in the ventrolateral medulla (VLM) contribute to the autonomic response to hypoxia. We hypothesized that 1) catecholaminergic neurons in the neonatal VLM are activated following IsH, 2) this activation is compromised following an acute loss of brain stem 5-HT, and 3) IsH induces cellular and/or transcriptomic plasticity within catecholaminergic and serotonergic neurons that are within or project to the VLM, respectively. To test these hypotheses, we treated rat pups with 6-fluorotryptophan, a tryptophan hydroxylase (TPH) inhibitor, and then exposed treated and vehicle controls to IsH or air. Along with immunohistochemistry to detect tyrosine hydroxylase (TH)- or Fos-positive neurons, we used RNA sequencing to resolve the effects of IsH and 5-HT deficiency on the expression of serotonergic and catecholaminergic system genes in the VLM. 5-HT deficiency compromised autoresuscitation and survival. IsH significantly increased the number of identifiable TH-positive VLM neurons, an effect enhanced by 5-HT deficiency (P = 0.003). Contrary to our hypothesis, 5-HT-deficient pups had significantly more Fos-positive neurons following IsH (P = 0.008) and more activated TH-positive neurons following IsH or air (P = 0.04). In both groups the expression of the 5-HT transporter and TPH2 was increased following IsH. In 5-HT-deficient pups, the expression of the inhibitory 5-HT1A receptor was decreased following IsH, while the expression of DOPA decarboxylase was increased. These data show that the serotonergic and catecholaminergic systems in the VLM of the neonatal rat are dynamically upregulated by IsH, potentially adapting cardiorespiratory responses to severe hypoxia. PMID:26968026

  15. Effect of acute nitrate supplementation on neurovascular coupling and cognitive performance in hypoxia.

    PubMed

    Lefferts, Wesley K; Hughes, William E; White, Corey N; Brutsaert, Tom D; Heffernan, Kevin S

    2016-02-01

    The matching of oxygen supply to neural demand (i.e., neurovascular coupling (NVC)) is an important determinant of cognitive performance. The impact of hypoxia on NVC remains poorly characterized. NVC is partially modulated by nitric oxide (NO), which may initially decrease in hypoxia. This study investigated the effect of acute NO-donor (nitrate) supplementation on NVC and cognitive function in hypoxia. Twenty healthy men participated in this randomized, double-blind, crossover design study. Following normoxic cognitive/NVC testing, participants consumed either nitrate (NIT) or a NIT-depleted placebo (PLA). Participants then underwent 120 min of hypoxia (11.6% ± 0.1% O2) and all cognitive/NVC testing was repeated. NVC was assessed as change in middle cerebral artery (MCA) blood flow during a cognitive task (incongruent Stroop) using transcranial Doppler. Additional computerized cognitive testing was conducted separately to assess memory, executive function, attention, sensorimotor, and social cognition domains. Salivary nitrite significantly increased following supplementation in hypoxia for NIT (+2.6 ± 1.0 arbitrary units (AU)) compared with PLA (+0.2 ± 0.3 AU; p < 0.05). Memory performance (-6 ± 13 correct) significantly decreased (p < 0.05) in hypoxia while all other cognitive domains were unchanged in hypoxia for both PLA and NIT conditions (p > 0.05). MCA flow increased during Stroop similarly in normoxia (PLA +5 ± 6 cm·s(-1), NIT +7 ± 7 cm·s(-1)) and hypoxia (PLA +5 ± 9 cm·s(-1), NIT +6 ± 7 cm·s(-1)) (p < 0.05) and this increase was not altered by PLA or NIT (p > 0.05). In conclusion, acute hypoxia resulted in significant reductions in memory concomitant with preservation of executive function, attention, and sensorimotor function. Hypoxia had no effect on NVC. Acute NIT supplementation had no effect on NVC or cognitive performance in hypoxia. PMID:26751937

  16. Effect of acute hypoxia on blood flow in vertebral and internal carotid arteries.

    PubMed

    Ogoh, Shigehiko; Sato, Kohei; Nakahara, Hidehiro; Okazaki, Kazunobu; Subudhi, Andrew W; Miyamoto, Tadayoshi

    2013-03-01

    Hypoxia changes the regional distribution of cerebral blood flow and stimulates the ventilatory chemoreflex, thereby reducing CO2 tension. We examined the effects of both hypoxia and isocapnic hypoxia on acute changes in internal carotid (ICA) and vertebral artery (VA) blood flow. Ten healthy male subjects underwent the following two randomly assigned respiratory interventions after a resting baseline period with room air: (i) hypoxia; and (ii) isocapnic hypoxia with a controlled gas mixture (12% O2; inspiratory mmHg). In the isocapnic hypoxia intervention, subjects were instructed to maintain the rate and depth of breathing to maintain the level of end-tidal partial pressure of CO2 ( ) during the resting baseline period. The ICA and VA blood flow (velocity × cross-sectional area) were measured using Doppler ultrasonography. The was decreased (-6.3 ± 0.9%, P < 0.001) during hypoxia by hyperventilation (minute ventilation +12.9 ± 2.2%, P < 0.001), while was unchanged during isocapnic hypoxia. The ICA blood flow was unchanged (P = 0.429), while VA blood flow increased (+10.3 ± 3.1%, P = 0.010) during hypoxia. In contrast, isocapnic hypoxia increased both ICA (+14.5 ± 1.4%, P < 0.001) and VA blood flows (+10.9 ± 2.4%, P < 0.001). Thus, hypoxic vasodilatation outweighed hypocapnic vasoconstriction in the VA, but not in the ICA. These findings suggest that acute hypoxia elicits an increase in posterior cerebral blood flow, possibly to maintain essential homeostatic functions of the brainstem. PMID:23143991

  17. Modification by Beta-Adrenergic Blockade of the Circulatory Responses to Acute Hypoxia in Man*

    PubMed Central

    Richardson, David W.; Kontos, Hermes A.; Raper, A. Jarrell; Patterson, John L.

    1967-01-01

    In 17 healthy men, beta-adrenergic blockade reduced significantly the tachycardia and the elevation of cardiac output associated with inhalation of 7.5% oxygen for 7 to 10 minutes. Hypoxia did not increase plasma concentrations of epinephrine or norepinephrine in six subjects. Furthermore, blockade of alpha and beta receptors in the forearm did not modify the vasodilation in the forearm induced by hypoxia, providing pharmacologic evidence that hypoxia of the degree and duration used was not associated with an increase in the concentrations of circulating catecholamines in man. Part of the increase in cardiac output and heart rate during acute hypoxia in man is produced by stimulation of beta-adrenergic receptors, probably by cardiac sympathetic nerves. The mechanism of the vasodilation in the forearm during hypoxia remains uncertain. PMID:4381183

  18. Effects of arundic acid, an astrocytic modulator, on the cerebral and respiratory functions in severe hypoxia.

    PubMed

    Fukushi, Isato; Takeda, Kotaro; Yokota, Shigefumi; Hasebe, Yohei; Sato, Yutaka; Pokorski, Mieczyslaw; Horiuchi, Jouji; Okada, Yasumasa

    2016-06-01

    Mild hypoxia increases ventilation, but severe hypoxia depresses it. The mechanism of hypoxic ventilatory depression, in particular, the functional role of the cerebrum, is not fully understood. Recent progress in glial physiology has provided evidence that astrocytes play active roles in information processing in various brain functions. We investigated the hypothesis that astrocytic activation is necessary to maintain the cerebral function and ventilation in hypoxia, by examining the responses of EEG and ventilation to severe hypoxia before and after administration of a modulator of astrocytic function, arundic acid, in unanesthetized mice. Ventilatory parameters were measured by whole body plethysmography. When hypoxic ventilatory depression occurred, gamma frequency band of EEG was suppressed. Arundic acid further suppressed ventilation, and the EEG power was suppressed in a dose-dependent manner. Arundic acid also suppressed hypoxia-induced c-Fos expression in the hypothalamus. We conclude that severe hypoxia suppresses the cerebral function which could reduce the stimulus to the brainstem resulting in ventilatory depression. Astrocytic activation in hypoxia may counteract both cerebral and ventilatory suppression. PMID:26592145

  19. Acute hypoxia during organogenesis affects cardiac autonomic balance in pregnant rats.

    PubMed

    Maslova, M V; Graf, A V; Maklakova, A S; Krushinskaya, Ya V; Sokolova, N A; Koshelev, V B

    2005-02-01

    Changes in ECG parameters were studied in pregnant rats exposed to acute hypobaric hypoxia during the period of organogenesis (gestation days 9 to 10). Rats with low, medium, and high tolerance to hypoxia exhibited pronounced autonomic nervous system imbalance, which become apparent as a loss of correlation between various parameters of ECG signals recorded at rest and during exposure to some stress factors existing under normal conditions. PMID:16027800

  20. Hypoxia is a modifier of SMN2 splicing and disease severity in a severe SMA mouse model

    PubMed Central

    Bebee, Thomas W.; Dominguez, Catherine E.; Samadzadeh-Tarighat, Somayeh; Akehurst, Kristi L.; Chandler, Dawn S.

    2012-01-01

    Spinal muscular atrophy (SMA) is a progressive neurodegenerative disease associated with low levels of the essential survival motor neuron (SMN) protein. Reduced levels of SMN is due to the loss of the SMN1 gene and inefficient splicing of the SMN2 gene caused by a C>T mutation in exon 7. Global analysis of the severe SMNΔ7 SMA mouse model revealed altered splicing and increased levels of the hypoxia-inducible transcript, Hif3alpha, at late stages of disease progression. Severe SMA patients also develop respiratory deficiency during disease progression. We sought to evaluate whether hypoxia was capable of altering SMN2 exon 7 splicing and whether increased oxygenation could modulate disease in a severe SMA mouse model. Hypoxia treatment in cell culture increased SMN2 exon 7 skipping and reduced SMN protein levels. Concordantly, the treatment of SMNΔ7 mice with hyperoxia treatment increased the inclusion of SMN2 exon 7 in skeletal muscles and resulted in improved motor function. Transfection splicing assays of SMN minigenes under hypoxia revealed that hypoxia-induced skipping is dependent on poor exon definition due to the SMN2 C>T mutation and suboptimal 5′ splice site. Hypoxia treatment in cell culture led to increased hnRNP A1 and Sam68 levels. Mutation of hnRNP A1-binding sites prevented hypoxia-induced skipping of SMN exon 7 and was found to bind both hnRNP A1 and Sam68. These results implicate hypoxic stress as a modulator of SMN2 exon 7 splicing in disease progression and a coordinated regulation by hnRNP A1 and Sam68 as modifiers of hypoxia-induced skipping of SMN exon 7. PMID:22763238

  1. Severe hypoxia during incremental exercise to exhaustion provokes negative post-exercise affects.

    PubMed

    Keramidas, Michail E; Stavrou, Nektarios A M; Kounalakis, Stylianos N; Eiken, Ola; Mekjavic, Igor B

    2016-03-15

    The post-exercise emotional response is mainly dependent on the intensity of the exercise performed; moderate exercise causes positive feelings, whereas maximal exercise may prompt negative affects. Acute hypoxia impairs peak O2 uptake (V̇O2peak), resulting in a shift to a lower absolute intensity at the point of exhaustion. Hence, the purpose of the study was to examine whether a severe hypoxic stimulus would influence the post-exercise affective state in healthy lowlanders performing an incremental exercise to exhaustion. Thirty-six male lowlanders performed, in a counter-balanced order and separated by a 48-h interval, two incremental exercise trials to exhaustion to determine their V̇O2peak, while they were breathing either room air (AIR; FiO2: 0.21), or a hypoxic gas mixture (HYPO; FiO2: 0.12). Before and immediately after each trial, subjects were requested to complete two questionnaires, based on how they felt at that particular moment: (i) the Profile of Mood States-Short Form, and (ii) the Activation Deactivation Adjective Check List. During the post-exercise phase, they also completed the Multidimensional Fatigue Inventory. V̇O2peak was significantly lower in the HYPO than the AIR trial (~15%; p<0.001). Still, after the HYPO trial, energy, calmness and motivation were markedly impaired, whereas tension, confusion, and perception of physical and general fatigue were exaggerated (p≤0.05). Accordingly, present findings suggest that an incremental exercise to exhaustion performed in severe hypoxia provokes negative post-exercise emotions, induces higher levels of perceived fatigue and decreases motivation; the affective responses coincide with the comparatively lower V̇O2peak than that achieved in normoxic conditions. PMID:26802281

  2. [Serum lactate level as a indicator of tissue hypoxia in severely ill patients].

    PubMed

    Bakker, J; Schieveld, S J; Brinkert, W

    2000-04-15

    Adequate oxygen supply to the tissues is of vital importance to survive critical illness and trauma. Shock can be defined as an imbalance between oxygen demand and oxygen supply. Clinical features of shock, like hypotension, tachycardia, cold clammy skin et cetera, are poorly correlated with presence of tissue hypoxia. A high lactate level is an early sign of tissue hypoxia. In severely ill patients tissue hypoxia is the most important cause of increased lactate levels. Increased blood lactate levels are related to increased mortality. Optimizing oxygen supply by fluid resuscitation is the intervention of first choice. PMID:10812440

  3. Tolerance of acute hypoxia while performing operator activity and after a prolonged period under altered gas environment conditions

    NASA Technical Reports Server (NTRS)

    Bloshchinskiy, P.; Golets, L.; Agadzhanyan, N. A.; Sergiyenko, A. V.

    1974-01-01

    Human and animal studies on physiological factors in resistance to acute hypoxia are elaborated. Results show that tolerance of acute hypoxia depends on gas composition and temperature in a sealed cabin, on the length of the stay and motive regime, and on the kind of operator and professional activity. After preliminary adaptation to hypoxia, resistance of the body increases not only to insufficiency of oxygen in inspired air, but also to the effects of other extremum factors of manned space flight.

  4. Acute hypoxia induces hypertriglyceridemia by decreasing plasma triglyceride clearance in mice

    PubMed Central

    Shin, Mi-Kyung; Yao, Qiaoling; Bevans-Fonti, Shannon; Poole, James; Drager, Luciano F.; Polotsky, Vsevolod Y.

    2012-01-01

    Obstructive sleep apnea (OSA) induces intermittent hypoxia (IH) during sleep and is associated with elevated triglycerides (TG). We previously demonstrated that mice exposed to chronic IH develop elevated TG. We now hypothesize that a single exposure to acute hypoxia also increases TG due to the stimulation of free fatty acid (FFA) mobilization from white adipose tissue (WAT), resulting in increased hepatic TG synthesis and secretion. Male C57BL6/J mice were exposed to FiO2 = 0.21, 0.17, 0.14, 0.10, or 0.07 for 6 h followed by assessment of plasma and liver TG, glucose, FFA, ketones, glycerol, and catecholamines. Hypoxia dose-dependently increased plasma TG, with levels peaking at FiO2 = 0.07. Hepatic TG levels also increased with hypoxia, peaking at FiO2 = 0.10. Plasma catecholamines also increased inversely with FiO2. Plasma ketones, glycerol, and FFA levels were more variable, with different degrees of hypoxia inducing WAT lipolysis and ketosis. FiO2 = 0.10 exposure stimulated WAT lipolysis but decreased the rate of hepatic TG secretion. This degree of hypoxia rapidly and reversibly delayed TG clearance while decreasing [3H]triolein-labeled Intralipid uptake in brown adipose tissue and WAT. Hypoxia decreased adipose tissue lipoprotein lipase (LPL) activity in brown adipose tissue and WAT. In addition, hypoxia decreased the transcription of LPL, peroxisome proliferator-activated receptor-γ, and fatty acid transporter CD36. We conclude that acute hypoxia increases plasma TG due to decreased tissue uptake, not increased hepatic TG secretion. PMID:22621867

  5. Acute effects of head-down tilt and hypoxia on modulators of fluid homeostasis

    NASA Technical Reports Server (NTRS)

    Whitson, P. A.; Cintron, N. M.; Pietrzyk, R. A.; Scotto, P.; Loeppky, J. A.

    1994-01-01

    In an effort to understand the interaction between acute postural fluid shifts and hypoxia on hormonal regulation of fluid homeostasis, the authors measured the responses to head-down tilt with and without acute exposure to normobaric hypoxia. Plasma atrial natriuretic peptide (ANP), cyclic guanosine monophosphate (cGMP), cyclic adenosine monophosphate (cAMP), plasma aldosterone (ALD), and plasma renin activity (PRA) were measured in six healthy male volunteers who were exposed to a head-down tilt protocol during normoxia and hypoxia. The tilt protocol consisted of a 17 degrees head-up phase (30 minutes), a 28 degrees head-down phase (1 hour), and a 17 degrees head-up recovery period (2 hours, with the last hour normoxic in both experiments). Altitude equivalent to 14,828 ft was simulated by having the subjects breathe an inspired gas mixture with 13.9% oxygen. The results indicate that the postural fluid redistribution associated with a 60-minute head-down tilt induces the release of ANP and cGMP during both hypoxia and normoxia. Hypoxia increased cGMP, cAMP, ALD, and PRA throughout the protocol and significantly potentiated the increase in cGMP during head-down tilt. Hypoxia had no overall effect on the release of ANP, but appeared to attenuate the increase with head-down tilt. This study describes the acute effects of hypoxia on the endocrine response during fluid redistribution and suggests that the magnitude, but not the direction, of these changes with posture is affected by hypoxia.

  6. Repeated acute hypoxia temporarily attenuates the ventilatory respiratory response to hypoxia in conscious newborn rats.

    PubMed

    Matsuoka, T; Yoda, T; Ushikubo, S; Matsuzawa, S; Sasano, T; Komiyama, A

    1999-07-01

    We asked whether repeated hypoxic exposures during the early neonatal periods could affect the ventilatory control, such as the lung volume-dependent ventilatory inhibition (HBR), pulmonary ventilation (VE), and CO2 production (VCO2). Within each litter of rats, one group of pups (experimental group H) was exposed to 6% O2 (30-min duration twice a day from postnatal d 1 to 4). The other group (control group C) was exposed to air. At 5 d after birth, the HBR was triggered by lung inflation via negative body surface pressure (10 cm H2O). Measurements of VE and VCO2 were done by plethysmography and the inflow-outflow CO2 difference, respectively. At 2 wk of age, VE and VCO2 measurements were repeated by the barometric technique and the inflow-outflow CO2 difference, respectively. Each conscious pup was breathing normoxia (21% O2) and then hypoxia (10% O2). Results were as follows: 1) during normoxia, HBR was stronger and both VE and VCO2 were higher in H pups than in C pups; 2) during hypoxia, the HBR of C was as in normoxia, whereas that of H was increased above the normoxic value; 3) during hypoxia, C maintained VE, whereas H decreased it; 4) in hypoxia, VCO2 was reduced significantly in both groups; 5) at 2 wk of age, VE and VCO2 did not differ between H and C during normoxia or in response to 10% hypoxia. We conclude that in rat pups, repeated hypoxic episodes can modify the HBR and, at least temporarily, reduce the VE response to hypoxia with a decrease in VCO2. The findings are in agreement with the view that repeated hypoxic exposures in the neonatal period could interfere with the development of respiratory control and could possibly be involved in the mechanisms of neonatal apnea or sudden infant death syndrome. PMID:10400145

  7. [Assessment and management of acute severe asthma].

    PubMed

    Kabe, J; Kudo, K

    1992-09-01

    In the management of acute severe asthma it is very important to start the treatment as soon as possible, by appropriate evaluation of the physical status and signs of airflow obstruction. We propose a guideline to be used by patients with asthma, emergency car crews, physicians and nurses to evaluate the severity and to choose the appropriate management of acute asthma, including intubation and mechanical ventilation, by the assessment of clinical features, as well as blood gas analysis and pulmonary function test. Several researchers have demonstrated that the additional administration of aminophylline to inhaled or subcutaneous beta 2-agonist bronchodilator during the first 4 hours of an attack provides no additional benefit compared to the administration of beta 2-agonist alone. In our retrospective study of 68 episodes of acute severe asthma in the last 5 years at our institute, however, the additional administration of aminophylline with beta 2-agonists was clearly shown to be effective with infrequent minor side effects. PMID:1360031

  8. Severe hypoxia induces complete antifolate resistance in carcinoma cells due to cell cycle arrest

    PubMed Central

    Raz, S; Sheban, D; Gonen, N; Stark, M; Berman, B; Assaraf, Y G

    2014-01-01

    Antifolates have a crucial role in the treatment of various cancers by inhibiting key enzymes in purine and thymidylate biosynthesis. However, the frequent emergence of inherent and acquired antifolate resistance in solid tumors calls for the development of novel therapeutic strategies to overcome this chemoresistance. The core of solid tumors is highly hypoxic due to poor blood circulation, and this hypoxia is considered to be a major contributor to drug resistance. However, the cytotoxic activity of antifolates under hypoxia is poorly characterized. Here we show that under severe hypoxia, gene expression of ubiquitously expressed key enzymes and transporters in folate metabolism and nucleoside homeostasis is downregulated. We further demonstrate that carcinoma cells become completely refractory, even at sub-millimolar concentrations, to all hydrophilic and lipophilic antifolates tested. Moreover, tumor cells retained sensitivity to the proteasome inhibitor bortezomib and the topoisomerase II inhibitor doxorubicin, which are independent of cell cycle. We provide evidence that this antifolate resistance, associated with repression of folate metabolism, is a result of the inability of antifolates to induce DNA damage under hypoxia, and is attributable to a hypoxia-induced cell cycle arrest, rather than a general anti-apoptotic mechanism. Our findings suggest that solid tumors harboring a hypoxic core of cell cycle-arrested cells may display antifolate resistance while retaining sensitivity to the chemotherapeutics bortezomib and doxorubicin. This study bears important implications for the molecular basis underlying antifolate resistance under hypoxia and its rational overcoming in solid tumors. PMID:24556682

  9. Afferent and efferent components of the cardiovascular reflex responses to acute hypoxia in term fetal sheep.

    PubMed Central

    Giussani, D A; Spencer, J A; Moore, P J; Bennet, L; Hanson, M A

    1993-01-01

    1. We studied the effects of acute isocapnic hypoxia on arterial and central venous pressures, carotid and femoral blood flows and heart rate in intact and carotid denervated fetal sheep between 118 and 125 days gestation, after pre-treatment with either saline, atropine or phentolamine. Electrocortical activity (ECoG) and the incidence of fetal breathing movements (FBM) were also compared between intact and carotid denervated fetuses. 2. There were no significant differences between intact and denervated fetuses in any variable measured during normoxia. Soon after the onset of hypoxia a marked bradycardia occurred in intact, but not in denervated fetuses. Femoral blood flow and femoral vascular resistance (perfusion pressure/femoral blood flow) increased in intact, but not in denervated fetuses. Carotid blood flow increased in both groups of fetuses during hypoxia, but carotid vascular resistance did not change. During hypoxia, the incidence of FBM and low-voltage ECoG was similarly reduced in both groups of fetuses. 3. Atropine produced a rise in fetal heart rate during the control period in intact but not in denervated fetuses. At the onset of hypoxia atropine prevented the initial bradycardia seen in intact fetuses. In denervated fetuses a further increase in heart rate occurred throughout the hypoxia. 4. All denervated fetuses treated with phentolamine died during the hypoxic challenge, but nine out of fourteen intact fetuses treated with phentolamine survived. 5. In intact fetuses which survived hypoxia after treatment with phentolamine, the increase in arterial blood pressure was smaller and the increase in femoral resistance did not occur. In these fetuses a rise in heart rate occurred in hypoxia. Carotid vascular resistance decreased during hypoxia after administration of phentolamine. 6. Our results indicate that the initial cardiovascular responses of the late gestation sheep fetus to hypoxia are reflex, and that the carotid chemoreceptors provide the

  10. Severe hypoxia induces chemo-resistance in clinical cervical tumors through MVP over-expression

    PubMed Central

    Lara, Pedro C; Lloret, Marta; Clavo, Bernardino; Apolinario, Rosa M; Henríquez-Hernández, Luis Alberto; Bordón, Elisa; Fontes, Fausto; Rey, Agustín

    2009-01-01

    Oxygen molecule modulates tumour response to radiotherapy. Higher radiation doses are required under hypoxic conditions to induce cell death. Hypoxia may inhibit the non-homologous end-joining DNA repair through down regulating Ku70/80 expression. Hypoxia induces drug resistance in clinical tumours, although the mechanism is not clearly elucidated. Vaults are ribonucleoprotein particles with a hollow barrel-like structure composed of three proteins: major vault protein (MVP), vault poly(ADP-ribose) polymerase, and telomerase associated protein-1 and small untranslated RNA. Over-expression of MVP has been associated with chemotherapy resistance. Also, it has been related to poor outcome in patients treated with radiotherapy alone. The aim of the present study was to assess the relation of Major Vault Protein expression and tumor hypoxia in clinical cervical tumors. MVP, p53 and angiogenesis, together with tumor oxygenation, were determined in forty-three consecutive patients suffering from localized cervix carcinoma. High MVP expression was related to severe hypoxia compared to low MVP expressing tumors (p = 0.022). Tumors over-expressing MVP also showed increased angiogenesis (p = 0.003). Besides it, in this study we show for the first time that severe tumor hypoxia is associated with high MVP expression in clinical cervical tumors. Up-regulation of MVP by hypoxia is of critical relevance as chemotherapy is currently a standard treatment for those patients. From our results it could be suggested that hypoxia not only induces increased genetic instability, oncogenic properties and metastatization, but through the correlation observed with MVP expression, another pathway of chemo and radiation resistance could be developed. PMID:19660100

  11. Severe hypoxia induces chemo-resistance in clinical cervical tumors through MVP over-expression.

    PubMed

    Lara, Pedro C; Lloret, Marta; Clavo, Bernardino; Apolinario, Rosa M; Henríquez-Hernández, Luis Alberto; Bordón, Elisa; Fontes, Fausto; Rey, Agustín

    2009-01-01

    Oxygen molecule modulates tumour response to radiotherapy. Higher radiation doses are required under hypoxic conditions to induce cell death. Hypoxia may inhibit the non-homologous end-joining DNA repair through down regulating Ku70/80 expression. Hypoxia induces drug resistance in clinical tumours, although the mechanism is not clearly elucidated. Vaults are ribonucleoprotein particles with a hollow barrel-like structure composed of three proteins: major vault protein (MVP), vault poly(ADP-ribose) polymerase, and telomerase associated protein-1 and small untranslated RNA. Over-expression of MVP has been associated with chemotherapy resistance. Also, it has been related to poor outcome in patients treated with radiotherapy alone. The aim of the present study was to assess the relation of Major Vault Protein expression and tumor hypoxia in clinical cervical tumors. MVP, p53 and angiogenesis, together with tumor oxygenation, were determined in forty-three consecutive patients suffering from localized cervix carcinoma. High MVP expression was related to severe hypoxia compared to low MVP expressing tumors (p = 0.022). Tumors over-expressing MVP also showed increased angiogenesis (p = 0.003). Besides it, in this study we show for the first time that severe tumor hypoxia is associated with high MVP expression in clinical cervical tumors. Up-regulation of MVP by hypoxia is of critical relevance as chemotherapy is currently a standard treatment for those patients. From our results it could be suggested that hypoxia not only induces increased genetic instability, oncogenic properties and metastatization, but through the correlation observed with MVP expression, another pathway of chemo and radiation resistance could be developed. PMID:19660100

  12. Alginate Microencapsulation of Human Islets Does Not Increase Susceptibility to Acute Hypoxia

    PubMed Central

    Hals, I. K.; Rokstad, A. M.; Strand, B. L.; Oberholzer, J.; Grill, V.

    2013-01-01

    Islet transplantation in diabetes is hampered by the need of life-long immunosuppression. Encapsulation provides partial immunoprotection but could possibly limit oxygen supply, a factor that may enhance hypoxia-induced beta cell death in the early posttransplantation period. Here we tested susceptibility of alginate microencapsulated human islets to experimental hypoxia (0.1–0.3% O2 for 8 h, followed by reoxygenation) on viability and functional parameters. Hypoxia reduced viability as measured by MTT by 33.8 ± 3.5% in encapsulated and 42.9 ± 5.2% in nonencapsulated islets (P < 0.2). Nonencapsulated islets released 37.7% (median) more HMGB1 compared to encapsulated islets after hypoxic culture conditions (P < 0.001). Glucose-induced insulin release was marginally affected by hypoxia. Basal oxygen consumption was equally reduced in encapsulated and nonencapsulated islets, by 22.0 ± 6.1% versus 24.8 ± 5.7%. Among 27 tested cytokines/chemokines, hypoxia increased the secretion of IL-6 and IL-8/CXCL8 in both groups of islets, whereas an increase of MCP-1/CCL2 was seen only with nonencapsulated islets. Conclusion. Alginate microencapsulation of human islets does not increase susceptibility to acute hypoxia. This is a positive finding in relation to potential use of encapsulation for islet transplantation. PMID:24364039

  13. Pazopanib-Induced Severe Acute Pancreatitis.

    PubMed

    Kawakubo, Kazumichi; Hata, Hiroo; Kawakami, Hiroshi; Kuwatani, Masaki; Kawahata, Shuhei; Kubo, Kimitoshi; Imafuku, Keisuke; Kitamura, Shinya; Sakamoto, Naoya

    2015-01-01

    Pazopanib is an oral angiogenesis inhibitor targeting vascular endothelial growth factor receptors, platelet-derived growth factor receptors, and c-Kit approved for the treatment of renal cell carcinoma and soft tissue sarcoma. Nonselective kinase inhibitors, such as sunitinib and sorafenib, are known to be associated with acute pancreatitis. There are few case reports of severe acute pancreatitis induced by pazopanib treatment. We present a case of severe acute pancreatitis caused by pazopanib treatment for cutaneous angiosarcoma. The patient was an 82-year-old female diagnosed with cutaneous angiosarcoma. She had been refractory to docetaxel treatment and began pazopanib therapy. Three months after pazopanib treatment, CT imaging of the abdomen showed the swelling of the pancreas and surrounding soft tissue inflammation without abdominal pain. After she continued pazopanib treatment for 2 months, she presented with nausea and appetite loss. Abdominal CT showed the worsening of the surrounding soft tissue inflammation of the pancreas. Serum amylase and lipase levels were 296 and 177 IU/l, respectively. She was diagnosed with acute pancreatitis induced by pazopanib treatment and was managed conservatively with discontinuation of pazopanib, but the symptoms did not improve. Subsequently, an abdominal CT scan demonstrated the appearance of a pancreatic pseudocyst. She underwent endoscopic ultrasound-guided pseudocyst drainage using a flared-end fully covered self-expandable metallic stent. Then, the symptoms resolved without recurrence. Due to the remarkable progress of molecular targeted therapy, the oncologist should know that acute pancreatitis was recognized as a potential adverse event of pazopanib treatment and could proceed to severe acute pancreatitis. PMID:26464570

  14. Maximum Running Speed of Captive Bar-Headed Geese Is Unaffected by Severe Hypoxia

    PubMed Central

    Hawkes, Lucy A.; Butler, Patrick J.; Frappell, Peter B.; Meir, Jessica U.; Milsom, William K.; Scott, Graham R.; Bishop, Charles M.

    2014-01-01

    While bar-headed geese are renowned for migration at high altitude over the Himalayas, previous work on captive birds suggested that these geese are unable to maintain rates of oxygen consumption while running in severely hypoxic conditions. To investigate this paradox, we re-examined the running performance and heart rates of bar-headed geese and barnacle geese (a low altitude species) during exercise in hypoxia. Bar-headed geese (n = 7) were able to run at maximum speeds (determined in normoxia) for 15 minutes in severe hypoxia (7% O2; simulating the hypoxia at 8500 m) with mean heart rates of 466±8 beats min−1. Barnacle geese (n = 10), on the other hand, were unable to complete similar trials in severe hypoxia and their mean heart rate (316 beats.min−1) was significantly lower than bar-headed geese. In bar-headed geese, partial pressures of oxygen and carbon dioxide in both arterial and mixed venous blood were significantly lower during hypoxia than normoxia, both at rest and while running. However, measurements of blood lactate in bar-headed geese suggested that anaerobic metabolism was not a major energy source during running in hypoxia. We combined these data with values taken from the literature to estimate (i) oxygen supply, using the Fick equation and (ii) oxygen demand using aerodynamic theory for bar-headed geese flying aerobically, and under their own power, at altitude. This analysis predicts that the maximum altitude at which geese can transport enough oxygen to fly without environmental assistance ranges from 6,800 m to 8,900 m altitude, depending on the parameters used in the model but that such flights should be rare. PMID:24710001

  15. Acute hypoxic gas breathing severely impairs cognition and task learning in humans.

    PubMed

    Turner, Clare E; Barker-Collo, Suzanne L; Connell, Charlotte J W; Gant, Nicholas

    2015-04-01

    Impairments in neural function are common when oxygen supply to the brain is reduced. This study examined neurocognitive processes that are vulnerable to oxygen deprivation. We induced moderate-to-severe hypoxia in healthy adults, thereby inducing impairments caused by low brain oxygen availability. 22 healthy adults participated in this matched-pairs study with a single-blind, randomised design. Baseline neurocognitive function was examined during a familiarisation trial and participants were assigned to hypoxia (10% O2) or sham (21% O2) groups. Neurocognitive performance was assessed via computerised test battery after 50 min of breathing a gas mixture that reduced arterial oxygen saturation by 20% (p<0.01). Hypoxia severely reduced performance across all neurocognitive domain scores; with significant drops in neurocognitive index (-20%), composite memory (-30%), verbal memory (-34%), visual memory (-23%), processing speed (-36%), executive function (-20%), psychomotor speed (-24%), reaction time (-10%), complex attention (-19%) and cognitive flexibility (-18%; all p<0.05). Practice effects were blocked by hypoxia but occurred in sham for information processing speed (+30%), executive function (+14%), psychomotor speed (+18%), reaction time (+5%), cognitive flexibility (+14%), and overall cognitive functioning (+9%; all p<0.05). Neuropsychological performance decrements caused by acute experimental hypoxia are comparable to cognitive domains impaired with high altitude exposure and mild traumatic brain injury. PMID:25660759

  16. Effect of acute systemic hypoxia on human cutaneous microcirculation and endothelial, sympathetic and myogenic activity.

    PubMed

    Paparde, Artūrs; Plakane, Līga; Circenis, Kristaps; Aivars, Juris Imants

    2015-11-01

    The regulation of cutaneous vascular tone impacts vascular vasomotion and blood volume distribution as a challenge to hypoxia, but the regulatory mechanisms yet remain poorly understood. A skin has a very compliant circulation, an increase in skin blood flow results in large peripheral displacement of blood volume, which could be controlled by local and systemic regulatory factors. The aim of this study was to determine the acute systemic hypoxia influence on blood flow in skin, local regulatory mechanism fluctuations and changes of systemic hemodynamic parameters. Healthy subjects (n=11; 24.9±3.7years old) participated in this study and procedures were performed in siting position. After 20min of acclimatization 15min of basal resting period in normoxia (pO2=21%) was recorded, followed by 20min in acute systemic hypoxia (pO2=12%), and after 15min of recovery period in normoxia (pO2=21%). HRV was used to evaluate autonomic nervous system activity to heart from systemic hemodynamic parameters which continuously evaluated cardiac output, total peripheral resistance and mean arterial blood pressure. Regional blood flow was evaluated by venous occlusion plethysmography and skin blood flow by laser-Doppler flowmetry. To evaluate local factor influences to cutaneous circulation wavelet analysis was used; fluctuations in the frequency intervals of 0.0095-0.021, 0.021-0.052, and 0.052-0.145Hz correspondingly represent endothelial, sympathetic, and myogenic activities. Our results from HRV data suggest that acute systemic hypoxia causes statistically significant increase of sympathetic (LF/HF; N1=0.46±0.25 vs. H=0.67±0.36; P=0.027) and decrease of parasympathetic (RMSSD; 80.0±43.1 vs. H=69.9±40.4, ms; P=0.009) outflow to heart. Acute hypoxia causes statistically significant increase of heart rate (RR interval; N1=960.3±174.5 vs. H=864.7±134.6, ms; P=0.001) and cardiac output (CO; N1=5.4 (5.2; 7.9) vs. H=6.7±1.4, l/min; P=0.020). Regional blood flow and vascular

  17. Ionoregulatory Aspects of the Osmorespiratory Compromise during Acute Environmental Hypoxia in 12 Tropical and Temperate Teleosts.

    PubMed

    Robertson, Lisa M; Val, Adalberto Luis; Almeida-Val, Vera F; Wood, Chris M

    2015-01-01

    In the traditional osmorespiratory compromise, as seen in the hypoxia-intolerant freshwater rainbow trout (Oncorhynchus mykiss), the branchial modifications that occur to improve O2 uptake during hypoxia result in unfavorable increases in the fluxes of ions and water. However, at least one hypoxia-tolerant freshwater species, the Amazonian oscar (Astronotus ocellatus), shows exactly the opposite: decreased branchial flux rates of ions, water, and nitrogenous wastes during acute hypoxia. In order to find out whether the two strategies were widespread, we used a standard 2-h normoxia, 2-h hypoxia (20%-30% saturation), 2-h normoxic recovery protocol to survey 10 other phylogenetically diverse tropical and temperate species. Unidirectional influx and efflux rates of Na(+) and net flux rates of K(+), ammonia, and urea-N were measured. The flux reduction strategy was seen only in one additional species, the Amazonian tambaqui (Colossoma macropomum), which is similarly hypoxia tolerant and lives in the same ion-poor waters as the oscar. However, five other species exhibited evidence of the increased flux rates typical of the traditional osmorespiratory compromise in the trout: the rosaceu tetra (Hyphessobrycon bentosi rosaceus), the moenkhausia tetra (Moenkhausia diktyota), the bluegill sunfish (Lepomis macrochirus), the zebra fish (Danio rerio), and the goldfish (Carassius auratus). Four other species exhibited no marked flux changes during hypoxia: the cardinal tetra (Paracheirodon axelrodi), the hemigrammus tetra (Hemigrammus rhodostomus), the pumpkinseed sunfish (Lepomis gibbosus), and the Atlantic killifish (Fundulus heteroclitus). Overall, a diversity of strategies exist; we speculate that these may be linked to differences in habitat and/or lifestyle. PMID:26052633

  18. Severe hypoxia and multiple infarctions resembling Creutzfeldt-Jakob disease.

    PubMed

    Mittelbronn, Michel; Capper, David; Bader, Benedikt; Schittenhelm, Jens; Haybaeck, Johannes; Weber, Petra; Meyermann, Richard; Kretzschmar, Hans A; Wietholter, Horst

    2008-01-01

    Although neuropathological examination is still required for the definite diagnosis of Creutzfeldt-Jakob disease (CJD), specialised clinical assessment predicts probable CJD. Here we present a 73-year-old female patient presenting with rapid cognitive decline, visual, acoustic and cerebellar disturbances, ataxia and EEG changes compatible with early CJD stages. MRI revealed hyperintensities within the thalami, hypothalami, corpora mammillaria, the tectum and the cortex. Initial neuropathological examination showed severe cortical and subcortical spongiosis. However, both immunohistochemistry and Western blotting showed no pathological prion protein. Finally, small infarctions affecting the tectum, tegmentum, corpora mammillaria and global hypoxic-ischaemic changes could be identified as the probable reason for the changes interpreted as CJD-related pathology. Hypoxic-ischaemic CNS alterations mainly affecting the supply area of the basilar artery should be ruled out in case of probable CJD. In addition, severe spongiosis can be misleading in the histological examination, suggesting the diagnosis of a prion-induced spongiform encephalopathy. PMID:18587709

  19. Chapter 14: Acute severe asthma (status asthmaticus).

    PubMed

    Shah, Rachna; Saltoun, Carol A

    2012-01-01

    Acute severe asthma, formerly known as status asthmaticus, is defined as severe asthma unresponsive to repeated courses of beta-agonist therapy such as inhaled albuterol, levalbuterol, or subcutaneous epinephrine. It is a medical emergency that requires immediate recognition and treatment. Oral or parenteral corticosteroids should be administered to all patients with acute severe asthma as early as possible because clinical benefits may not occur for a minimum of 6-12 hours. Approximately 50% of episodes are attributable to upper respiratory infections, and other causes include medical nonadherence, nonsteroidal anti-inflammatory exposure in aspirin-allergic patients, allergen exposure (especially pets) in severely atopic individuals, irritant inhalation (smoke, paint, etc.), exercise, and insufficient use of inhaled or oral corticosteroids. The patient history should be focused on acute severe asthma including current use of oral or inhaled corticosteroids, number of hospitalizations, emergency room visits, intensive-care unit admissions and intubations, the frequency of albuterol use, the presence of nighttime symptoms, exercise intolerance, current medications or illicit drug use, exposure to allergens, and other significant medical conditions. Severe airflow obstruction may be predicted by accessory muscle use, pulsus paradoxus, refusal to recline below 30°, a pulse >120 beats/min, and decreased breath sounds. Physicians' subjective assessments of airway obstruction are often inaccurate. More objective measures of airway obstruction via peak flow (or forced expiratory volume in 1 second) and pulse oximetry before oxygen administration usually are helpful. Pulse oximetry values >90% are less commonly associated with problems although CO(2) retention and a low Pao(2) may be missed. PMID:22794687

  20. Protective effects of thoracic epidural anesthesia on hypoxia-induced acute lung injury in rabbits

    PubMed Central

    WANG, LIJUN; CANG, JING; XUE, ZHANGGANG

    2016-01-01

    The mechanism underlying the effect of thoracic epidural anesthesia (TEA) on hypoxia-induced acute lung injury (ALI) is currently unknown. In the present study, a rabbit acute lung injury model was established to investigate the effects of TEA on inflammatory factors, pulmonary surfactant and ultrastructure. A total of 56 rabbits were randomly assigned to four groups (n=14 per group): Control group (Group C), hypoxia group (Group H), sevoflurane group (Group S) and combined sevoflurane-epidural anesthesia group (Group ES). The ALI model was considered to have been successfully induced when the ratio of arterial oxygen partial pressure to fractional inspired oxygen was <300. The correct placement of a catheter for TEA was confirmed using epidurography. ALI was maintained for 3 h. Arterial blood samples were collected from all groups during spontaneous breathing (T0) and at 3 h after ALI induction (T5) in order to evaluate the serum levels of interleukin (IL)-6, IL-8 and IL-10. Bronchoalveolar lavage fluid was harvested to determine the total phospholipid, saturated phosphatidylcholine and total protein levels. Furthermore, the dry/wet weight ratio and the mRNA expression levels of IL-6, IL-8 and IL-10 in the lung tissue were determined using ELISA. In addition, light and transmission electron microscopy and histological techniques were used to examine the morphology of alveolar type II cells in the rat lung tissue. The results indicate that changes of serum IL-6, IL-8 and IL-10 levels following ALI were consistent with the changes in the mRNA expression levels of IL-6, IL-8 and IL-10 in the lung tissue. TEA attenuated these changes and thus reduced the severity of the ALI. In addition, TEA improved the alveolar structure, reduced the number of polymorphonuclear cells and mitigated the damage of lamellar bodies. In summary, the results of the present study indicate that TEA reduces lung tissue damage by inhibiting systemic and local inflammation, decreasing the

  1. Survival in acute and severe low o environment: use of a genetic model system.

    PubMed

    Azad, Priti; Haddad, Gabriel G

    2009-10-01

    Hypoxia whether present during physiologic states (e.g., embryogenesis) or during pathologic states (e.g., obstructive sleep apnea and sickle cell anemia), challenges the vertebrate or invertebrate organism. Clearly, hypoxia can lead to sublethal cell injury or death and consequently organ or systemic injury and failure, depending on severity. We discovered that the adult Drosophila melanogaster is tolerant to a low O(2) environment, withstanding approximately 3-4 hours of total O(2) deprivation or anoxia without showing any evidence of cell injury. This opened major avenues for us since the Drosophila has been used so effectively in so many relevant research areas. We investigated the changes in gene expression in D. melanogaster after severe (1% O(2)) intermittent or constant hypoxia treatment for 2.5 hours. Our microarray analysis has identified multiple gene families that are up- or downregulated in response to acute constant (CH) and intermittent hypoxia (IH). We observed that even for short-term the gene expression response to IH and CH varied not only in the number of genes but also type of gene families. Furthermore, by utilizing powerful Drosophila genetic tools we studied the role of single genes (up- or downregulated in arrays) in survival under either paradigm in adult flies. We observed significant increased adult survival (as compared to controls) of P-element lines for Hsp70 and Hsp23 genes during CH and Mdr49 and l (2)08717 genes during IH. This suggests that the increased transcript levels as observed in array data after either paradigm play an important role under severe hypoxia. Indeed, we found for example that over-expressing Hsp70 in vivo in specific fly organs (such as heart) significantly increased adult survival during CH as compared to controls. These data provide further clues about the mechanisms by which intermittent and constant hypoxia lead to cell injury and morbidity or adaptation and survival. PMID:19845605

  2. Adipogenesis, lipogenesis and lipolysis is stimulated by mild but not severe hypoxia in 3T3-L1 cells.

    PubMed

    Weiszenstein, Martin; Musutova, Martina; Plihalova, Andrea; Westlake, Katerina; Elkalaf, Moustafa; Koc, Michal; Prochazka, Antonin; Pala, Jan; Gulati, Sumeet; Trnka, Jan; Polak, Jan

    2016-09-16

    In-vitro investigation of the effects of hypoxia is limited by physical laws of gas diffusion and cellular O2 consumption, making prolonged exposures to stable O2 concentrations impossible. Using a gas-permeable cultureware, chronic effects of mild and severe hypoxia on triglyceride accumulation, lipid droplet size distribution, spontaneous lipolysis and gene expression of adipocyte-specific markers were assessed. 3T3-L1 cells were differentiated under 20%, 4% or 1% O2 using a gas-permeable cultureware. Triglyceride accumulation, expression of genes characteristic for advanced adipocyte differentiation and involvement of key lipogenesis enzymes were assessed after exposures. Lipogenesis increased by 375% under mild hypoxia, but dropped by 43% in severe hypoxia. Mild, but not severe, hypoxia increased formation of large lipid droplets 6.4 fold and strongly induced gene expression of adipocyte-specific markers. Spontaneous lipolysis increased by 488% in mild, but only by 135% in severe hypoxia. Inhibition of ATP-dependent citrate lyase suppressed hypoxia-induced lipogenesis by 81% and 85%. Activation of HIF inhibited lipogenesis by 59%. Mild, but not severe, hypoxia stimulates lipolysis and promotes adipocyte differentiation, probably through excess of acetyl-CoA originating from tricarboxylic acid cycle independently of HIF activation. PMID:27498031

  3. Severe acute pancreatitis: Clinical course and management

    PubMed Central

    Beger, Hans G; Rau, Bettina M

    2007-01-01

    Severe acute pancreatitis (SAP) develops in about 25% of patients with acute pancreatitis (AP). Severity of AP is linked to the presence of systemic organ dysfunctions and/or necrotizing pancreatitis pathomorphologically. Risk factors determining independently the outcome of SAP are early multi-organ failure, infection of necrosis and extended necrosis (> 50%). Up to one third of patients with necrotizing pancreatitis develop in the late course infection of necroses. Morbidity of SAP is biphasic, in the first week strongly related to early and persistence of organ or multi-organ dysfunction. Clinical sepsis caused by infected necrosis leading to multi-organ failure syndrome (MOFS) occurs in the later course after the first week. To predict sepsis, MOFS or deaths in the first 48-72 h, the highest predictive accuracy has been objectified for procalcitonin and IL-8; the Sepsis-Related Organ Failure Assessment (SOFA)-score predicts the outcome in the first 48 h, and provides a daily assessment of treatment response with a high positive predictive value. Contrast-enhanced CT provides the highest diagnostic accuracy for necrotizing pancreatitis when performed after the first week of disease. Patients who suffer early organ dysfunctions or at risk of developing a severe disease require early intensive care treatment. Early vigorous intravenous fluid replacement is of foremost importance. The goal is to decrease the hematocrit or restore normal cardiocirculatory functions. Antibiotic prophylaxis has not been shown as an effective preventive treatment. Early enteral feeding is based on a high level of evidence, resulting in a reduction of local and systemic infection. Patients suffering infected necrosis causing clinical sepsis, pancreatic abscess or surgical acute abdomen are candidates for early intervention. Hospital mortality of SAP after interventional or surgical debridement has decreased in high volume centers to below 20%. PMID:17876868

  4. Sleep state dependence of ventilatory long-term facilitation following acute intermittent hypoxia in Lewis rats

    PubMed Central

    Nakamura, A.; Olson, E. B.; Terada, J.; Wenninger, J. M.; Bisgard, G. E.

    2010-01-01

    Ventilatory long-term facilitation (vLTF) is a form of respiratory plasticity induced by acute intermittent hypoxia (AIH). Although vLTF has been reported in unanesthetized animals, little is known concerning the effects of vigilance state on vLTF expression. We hypothesized that AIH-induced vLTF is preferentially expressed in sleeping vs. awake male Lewis rats. Vigilance state was assessed in unanesthetized rats with chronically implanted EEG and nuchal EMG electrodes, while tidal volume, frequency, minute ventilation (V̇e), and CO2 production were measured via plethysmography, before, during, and after AIH (five 5-min episodes of 10.5% O2 separated by 5-min normoxic intervals), acute sustained hypoxia (25 min of 10.5% O2), or a sham protocol without hypoxia. Vigilance state was classified as quiet wakefulness (QW), light and deep non-rapid eye movement (NREM) sleep (l-NREM and d-NREM sleep, respectively), or rapid eye movement sleep. Ventilatory variables were normalized to pretreatment baseline values in the same vigilance state. During d-NREM sleep, vLTF was observed as a progressive increase in V̇e post-AIH (27 ± 5% average, 30–60 min post-AIH). In association, V̇e/V̇co2 (36 ± 2%), tidal volume (14 ± 2%), and frequency (7 ± 2%) were increased 30–60 min post-AIH during d-NREM sleep. vLTF was significant but less robust during l-NREM sleep, was minimal during QW, and was not observed following acute sustained hypoxia or sham protocols in any vigilance state. Thus, vLTF is state-dependent and pattern-sensitive in unanesthetized Lewis rats, with the greatest effects during d-NREM sleep. Although the physiological significance of vLTF is not clear, its greatest significance to ventilatory control is most likely during sleep. PMID:20360430

  5. Acute Effects of Normobaric Hypoxia on Hand-Temperature Responses During and After Local Cold Stress

    PubMed Central

    Kölegård, Roger; Mekjavic, Igor B.; Eiken, Ola

    2014-01-01

    Abstract Keramidas, Michail E, Roger Kölegård, Igor B. Mekjavic, and Ola Eiken. Acute effects of normobaric hypoxia on hand-temperature responses during and after local cold stress. High Alt Med Biol. 15:183–191, 2014.—The purpose was to investigate acute effects of normobaric hypoxia on hand-temperature responses during and after a cold-water hand immersion test. Fifteen males performed two right-hand immersion tests in 8°C water, during which they were inspiring either room air (Fio2: 0.21; AIR), or a hypoxic gas mixture (Fio2: 0.14; HYPO). The tests were conducted in a counterbalanced order and separated by a 1-hour interval. Throughout the 30-min cold-water immersion (CWI) and the 15-min spontaneous rewarming (RW) phases, finger-skin temperatures were measured continuously with thermocouple probes; infrared thermography was also employed during the RW phase to map all segments of the hand. During the CWI phase, the average skin temperature (Tavg) of the fingers did not differ between the conditions (AIR: 10.2±0.5°C, HYPO: 10.0±0.5°C; p=0.67). However, Tavg was lower in the HYPO than the AIR RW phase (AIR: 24.5±3.4°C; HYPO: 22.0±3.8°C; p=0.002); a response that was alike in all regions of the immersed hand. Accordingly, present findings suggest that acute exposure to normobaric hypoxia does not aggravate the cold-induced drop in hand temperature of normothermic males. Still, hypoxia markedly impairs the rewarming responses of the hand. PMID:24666109

  6. [Concept of SIRS and severe acute pancreatitis].

    PubMed

    Hirota, Masahiko; Sugita, Hiroki; Maeda, Keisuke; Ichibara, Atsushi; Ogawa, Michio

    2004-11-01

    Acute pancreatitis is a potentially fatal disease, the severity of which ranges from a mild edematous form to a severe necrotizing form. Most patients develop systemic inflammatory response syndrome (SIRS), which is induced by proinflammatory cytokines. The cytokine production can be induced by activation of Toll-like receptor. The breakdown products of the pancreatic and peripancreatic tissues by proteases might be the agonists. Cytokines are supposed to be produced as a biological defense system. However, cytokines may often evoke organ failure and/or immunosuppressive state, if they would be produced excessively. To express this complicated pathologic condition, Ogawa proposed a concept of LISIS(local inflammation-induced systemic immunosuppression syndrome). We have to pay attention to such aspects in the management of this disease. PMID:15552899

  7. CO2-O2 interactions in extension of tolerance to acute hypoxia

    NASA Technical Reports Server (NTRS)

    Lambertsen, C. J.

    1995-01-01

    Objectives and results of experimental projects a re summarized. The scope of information desired included (1) physiological and performance consequences of exposures to simulated microgravity, in rest and graded physical activity, (2) separate influences of graded degrees of atmospheric hypercapnia and hypoxia, and (3) composite effects of hypoxia and hypercapnia. The research objectives were selected for close relevance to existing quantitative information concerning interactions of hypercapnia and hypoxia on respiratory and brain circulatory control. They include: (1) to determine influences of normoxic immersion on interrelations of pulmonary ventilation, arterial PCO2 and PO2, and brain blood flow, in rest and physical work; (2) to determine influence of normoxic immersion on respiratory reactivity to atmospheric hypercapnia at rest; (3) to determine influence of atmospheric hypoxia on respiratory reactivity to hypercapnia at rest and in work; and (4) to provide physiological baselines of data concerning adaptations in acute exposures to aid in investigation of rates of adaptation or deteriorations in physiological or performance capability during subsequent multi-day exposures. A list of publications related to the present grant period is included along with an appendix describing the Performance Measurement System (human perceptual, cognitive and psychomotor functions).

  8. Hypoxia regulates proliferation of acute myeloid leukemia and sensitivity against chemotherapy.

    PubMed

    Drolle, Heidrun; Wagner, Michaela; Vasold, Jochen; Kütt, Alexander; Deniffel, Christian; Sotlar, Karl; Sironi, Silvia; Herold, Tobias; Rieger, Christina; Fiegl, Michael

    2015-07-01

    Reduced oxygen partial pressure (pO2, hypoxia) is an important component of the bone marrow microenvironment and the hematopoietic stem cell niche. It is unclear whether this applies to the leukemic stem cell as well and if differences in pO2 between the normal hematopoetic and the leukemic stem cell niche exits. Here, we demonstrate that while there is no detectable difference in the hypoxic level of bone marrow infiltrated by acute myeloid leukemia (AML) and healthy bone marrow, physiological hypoxia of 1% O2 itself leads to cell cycle arrest of AML blasts (both cell lines and primary AML samples) in the G0/G1 phase with upregulation of p27 and consecutive decrease of cells in the S phase. Hence, susceptibility of AML blasts toward cytarabine as S phase dependent drug is significantly decreased as shown by decreased cytotoxicity in vitro. In addition, cells exposed to hypoxia activate PI3K/Akt and increase expression of anti-apoptotic XIAP. Inhibition of PI3K can restore cytarabine sensitivity of AML blasts at hypoxic conditions. In conclusion, hypoxia mediated effects encountered in the bone marrow might contribute to chemoresistance of AML blasts. PMID:25982178

  9. Severe acute respiratory syndrome in a naval diver.

    PubMed

    Chim, Harvey; Soo, Kian Hing; Low, Edwin; Chan, Gregory

    2006-06-01

    Severe acute respiratory syndrome (SARS) is a highly infectious, rapidly progressive, emerging disease. Early diagnosis and preventive measures are key for treatment and minimization of secondary spread. In the context of the armed forces, aggressive containment measures are essential to prevent an outbreak. In this study, we present the first reported case, to our knowledge, of SARS in a naval diver. The special physical requirements for divers and the potential complications associated with deep sea diving necessitate extensive investigation before certification of fitness for diving after SARS. In the early recovery period, potential problems during diving are caused by inadequate lung ventilation in relation to exercise level and increased breathing resistance attributable to weak respiratory muscles, with corresponding risk of hypoxia and hypercapnia, as well as decreased ability to respond to nonrespiratory problems during diving. Problems in the late recovery period include increased risk of diving complications (such as pulmonary barotrauma) resulting from fibrosis and scarring within the lung parenchyma, which are known complications of SARS. From our experience, we suggest that computed tomographic scans of the thorax, lung function tests, and careful follow-up monitoring should play a vital role in the assessment of patients during the convalescent period, before certification of fitness to dive. PMID:16808126

  10. [ASSOCIATED RESPIRATORY AND HEMODYNAMICS RESPONSE TO ACUTE NORMOBARIC PROGRESSIVE HYPOXIA IN ANESTHETIZED RATS].

    PubMed

    Donina, Zh A; Baranova, E V; Aleksandrova, N P

    2015-10-01

    The interdependent reactions of the cardiorespiratory system during experimental simulation of progressive acute hypoxia were studied in anesthetized Wistar rats. The results indicate that the extremely low oxygen content in the inhaled gas mixture to less than 6% lead to terminal sedation and apnea. After the cessation of hypoxic exposure were observed spontaneous autoresuscitation. Effects of progressive hypoxia, is an example of a multi-component interdependent reactions of the cardiorespiratory system, which are based on the respiratory and vasomotor center function disturbance and the predominance of parasympathetic influences on the heart. The obtained data can be used as a model of hypoxic apnea to examine the influence of physiologically active substances on the cardiorespiratory system at disease pathology. PMID:26827496

  11. Exploratory proteomic analysis of hypobaric hypoxia and acute mountain sickness in humans

    PubMed Central

    Subudhi, Andrew W.; Hill, Ryan C.; Wilson, Megan J.; Dimmen, Andrew C.; Hansen, Kirk C.; Roach, Robert C.

    2013-01-01

    Our objective in this exploratory study was to identify novel biomarkers of importance for acute mountain sickness (AMS) using discovery-based proteomic methods. Peripheral blood samples were collected and AMS symptoms were assessed in 20 healthy volunteers prior to [−15 h (baseline) and 0 h; 1,609 m; barometric pressure = 625 mmHg] and after a 9-h exposure to hypobaric hypoxia (9 h; 4,875 m; barometric pressure = 425 mmHg). AMS status was assessed using the Lake Louise Questionnaire. Plasma samples were pooled according to AMS status at each time point. Protein composition of the samples was determined by a GeLC-MS/MS approach using two analytical platforms (LTQ-XL linear ion trap mass spectrometer and a LTQ-FT ultra hybrid mass spectrometer) for technical replication. Spectral counting was used to make semiquantitative comparisons of protein abundance between AMS-susceptible (AMS) and AMS-resistant (AMS·R) subjects with exposure to hypobaric hypoxia. After 9 h of hypoxia, the abundance of proteins with antioxidant properties (i.e., peroxiredoxin 6, glutathione peroxidase, and sulfhydryl oxidase 1) rose in AMS but not AMS·R. Our exploratory analyses suggest that exposure to hypobaric hypoxia enhances enzymatic antioxidant systems in AMS vs. AMS·R, which, we propose, may be an overcompensation for hypoxia-induced oxidant production. On the basis of our findings we 1) speculate that quenching oxidant activity may have adverse downstream effects that are of pathophysiological importance for AMS such as interrupting oxidant-sensitive cell signaling and gene transcription and 2) question the existing assumption that increased oxidant production in AMS is pathological. PMID:24265281

  12. Dynamic regulation of metabolic efficiency explains tolerance to acute hypoxia in humans.

    PubMed

    Schiffer, Tomas A; Ekblom, Björn; Lundberg, Jon O; Weitzberg, Eddie; Larsen, Filip J

    2014-10-01

    The maximum power principle dictates that open biological systems tend to self-organize to a level of efficiency that allows maximal power production. Applying this principle to cellular energetics and whole-body physiology would suggest that for every metabolic challenge, an optimal efficiency exists that maximizes power production. On exposure to hypoxia, it would be favorable if metabolic efficiency would rapidly adjust so as to better preserve work performance. We tested this idea in humans by measuring metabolic efficiency and exercise tolerance under normoxic (Fio2=20.9%) and hypoxic (Fio2=16%) conditions, where Fio2 is fraction of inhaled oxygen. The results were compared with respirometric analyses of skeletal muscle mitochondria from the same individuals. We found that among healthy trained subjects (n=14) with a wide range of metabolic efficiency (ME), those with a high ME during normoxic exercise were able to better maintain exercise capacity (Wmax) in hypoxia. On hypoxic exposure, these subjects acutely decreased their efficiency from 19.2 to 17.4%, thereby likely shifting it closer to a degree of efficiency where maximal power production is achieved. In addition, mitochondria from these subjects had a lower intrinsic respiration compared to subjects that showed a large drop in Wmax in hypoxia An acute shift in efficiency was also demonstrated in isolated mitochondria exposed to physiological levels of hypoxia as P/O ratio increased from 0.9 to 1.3 with hypoxic exposure. These findings suggest the existence of a physiological adaptive response by which metabolic efficiency is dynamically optimized to maximize power production. PMID:24970395

  13. Slow channel inhibitor effects on brain function: tolerance to severe hypoxia in the rat.

    PubMed Central

    Cartheuser, C. F.

    1988-01-01

    1. The protective effects of ten slow channel inhibitor drugs against severe progressive hypoxia were investigated in rats breathing spontaneously during light anaesthesia. Respiration, heart rate, electrocorticogram (ECoG) and/or electroencephalogram (EEG) were recorded. 2. Tolerance times were monitored from hypoxia onset until cessation of respiration, ECoG, EEG synchronization, and 'background-EEG'. Drugs were administered i.v. 5 min before the onset of hypoxia. 3. Verapamil, gallopamil, and nimodipine resulted in a significant increase of tolerance times; fendiline and bepridil showed a small increase (not significant); bencyclan and prenylamine were ineffective; cinnarizine and diltiazem slightly reduced tolerance times as did flunarizine at low doses. 4. At protective doses, verapamil, gallopamil, and nimodipine significantly raised the respiration rate but had little or no cardiac depressor effects. Bencyclan showed ventilatory drive but cardiocirculatory depression. A clear-cut ventilatory drive did not occur with the other ineffective slow channel inhibitors. 5. It is suggested that the protective actions observed were not due to slow channel inhibition per se, nor to spasmolytic potency or increased cerebral blood flow. Ventilatory drive associated with other cardiopulmonary actions which secondarily raise the brain oxygen supply are likely to be responsible for this effect. PMID:3264735

  14. Effect of acute progestational hypoxia on the content of biogenic amines in the brain of albino rat pups: Peptide correction.

    PubMed

    Maslova, M V; Graf, A V; Sokolova, N A; Goncharenko, E N; Shestakova, S V; Kudryashova, N Yu; Andreeva, L A

    2003-08-01

    We studied the effect of exposure to acute hypobaric hypoxia in the progestational period on the content of biogenic amines in the brainstem and cerebral cortex in rat pups of different age. The possibility of correcting hypoxia-induced changes with regulatory peptides was evaluated. We found that early antenatal hypoxia disturbs maturation of catecholaminergic systems in the brain. It should be emphasized that the differences from the control varied depending on the age of rat pups. Single intranasal administration of Semax heptapeptides and beta-casomorphine-7 to pregnant females prevented changes in the content of biogenic amines in CNS of the offspring during postnatal ontogeny. PMID:14631488

  15. Comparison of Acute Alterations in Left Ventricular Relaxation and Diastolic Chamber Stiffness Induced by Hypoxia and Ischemia

    PubMed Central

    Serizawa, Takashi; Vogel, W. Mark; Apstein, Carl S.; Grossman, William

    1981-01-01

    further decline in left ventricular systolic pressure, and no increase was noted in postpacing LVEDP. Changes in lactate extraction ratio were much smaller in magnitude than with hypoxia and constant coronary perfusion. In two experiments (one at normal coronary flow and one at 15 ml/min), left ventricular systolic pressure did not change markedly from control when tachycardia was superimposed, and postpacing LVEDP showed a marked rise (to > 25 mm Hg), which gradually recovered over 1−2 min at the control heart rate. From these results, we conclude that left ventricular chamber stiffness increases when myocardial O2 demand exceeds supply. This change is usually masked in ischemic (reduced coronary flow) preparations, perhaps because of reduced turgor of the coronary vascular bed, marked reductions in systolic work (and therefore myocardial O2 requirements), and local accumulation of hydrogen ion and metabolites following acute severe reduction of coronary flow. The increased chamber stiffness during hypoxia is accompanied by marked slowing of relaxation, with increased diastolic pressure relative to volume persisting throughout diastole. PMID:7251868

  16. Exhaled nitric oxide decreases upon acute exposure to high-altitude hypoxia.

    PubMed

    Brown, Daniel E; Beall, Cynthia M; Strohl, Kingman P; Mills, Phoebe S

    2006-01-01

    Nitric oxide (NO) is a vasodilator that plays a role in blood flow and oxygen delivery. Acute hypoxia down regulates NO synthesis, a response that may exacerbate hypoxic stress by decreasing blood flow. This study was designed to test the hypotheses that pulmonary NO decreases upon acute exposure to high-altitude hypoxia and that relatively low levels of NO at altitude are associated with greater stress as reflected in more symptoms of acute mountain sickness (AMS). A sample of 47 healthy, adult, nonsmoking, sea-level residents provided measurements at sea level, at 2,800 m, and at 0-, 2-, and 3-h exposure times at 4,200 m altitude on Mauna Kea, Hawaii. Measurements were made of exhaled NO, oxygen saturation of hemoglobin, heart rate, and reported symptoms of AMS. The partial pressure of NO concentration in exhaled breath decreased significantly from a sea level mean of 4.2 nmHg to 3.8 nmHg at 2,800 m and 3.4 nmHg at 4,200 m. NO concentration in exhaled breath did not change significantly over a 3-h exposure at 4,200 m and recovered to pre-exposure baseline upon return to sea level. There was no significant association between the level of NO exhaled and the number of self-reported symptoms of AMS during this brief exposure. PMID:16493632

  17. Acute Mountain Sickness, Hypoxia, Hypobaria and Exercise Duration each Affect Heart Rate.

    PubMed

    DiPasquale, D M; Strangman, G E; Harris, N S; Muza, S R

    2015-07-01

    In this study, we quantified the changes in post-exercise resting heart rate (HRrst) associated with acute mountain sickness (AMS), and compared the effects of hypobaric hypoxia (HH) and normobaric hypoxia (NH) on HRrst. We also examined the modulating roles of exercise duration and exposure time on HRrst. Each subject participated in 2 of 6 conditions: normobaric normoxia (NN), NH, or HH (4 400 m altitude equivalent) combined with either 10 or 60 min of moderate cycling at the beginning of an 8-h exposure. AMS was associated with a 2 bpm higher HRrst than when not sick, after taking into account the ambient environment, exercise duration, and SpO2. In addition, HRrst was elevated in both NH and HH compared to NN with HRrst being 50% higher in HH than in NH. Participating in long duration exercise led to elevated resting HRs (0.8-1.4 bpm higher) compared with short exercise, while short exercise caused a progressive increase in HRrst over the exposure period in both NH and HH (0.77-1.2 bpm/h of exposure). This data suggests that AMS, NH, HH, exercise duration, time of exposure, and SpO2 have independent effects on HRrst. It further suggests that hypobaria exerts its own effect on HRrst in hypoxia. Thus NH and HH may not be interchangeable environments. PMID:25837245

  18. Pterostilbene as treatment for severe acute pancreatitis.

    PubMed

    Lin, Y J; Ding, Y; Wu, J; Ning, B T

    2016-01-01

    Acute pancreatitis (AP) has a fast onset and progression, which lead to an unfavorable prognosis. Therefore, the development of novel drugs for its treatment is critical. As a homologous derivative of resveratrol, pterostilbene exerts a variety of effects including anti-inflammatory, antioxidant, and antitumor effects. This study investigated the potential of pterostilbene for treatment of severe AP (SAP) and related mechanisms. Effects of pterostilbene were evaluated in a Wistar rat model of AP. Serum levels of amylase (AMY), creatinine (Cr), and alanine aminotransferase (ALT) were quantified. Furthermore, serum levels of tumor necrosis factor (TNF)-a and interleukin (IL)-1b were quantified using enzyme-linked immunosorbent assay. Nuclear factor (NF)-kB expression in pancreatic tissues was quantified by real-time PCR and western blotting. The production of reactive oxygen species (ROS) was determined using a spectrometer, while superoxide dismutase (SOD) activity was assayed. In the AP rat model, the expression of inflammatory markers TNF-a and IL-1b, expression of NF-kB, and serum indices (AMY, Cr, and ALT) increased compared to the corresponding levels in the control group (P < 0.05). Pterostilbene reduced serum levels of TNF-a and IL-1b; decreased NF-kB gene expression, serum indices, and ROS generation; and increased SOD activity in a dose-dependent manner. In conclusion, pterostilbene can alleviate SAP-induced tissue damage by decreasing the inflammatory response and by promoting antioxidation leading to the protection of pancreatic tissues. PMID:27525946

  19. Comparative studies of hemolymph physiology response and HIF-1 expression in different strains of Litopenaeus vannamei under acute hypoxia.

    PubMed

    Wei, Lin; Li, Yuhu; Qiu, Liguo; Zhou, Hailong; Han, Qian; Diao, Xiaoping

    2016-06-01

    Litopenaeus vannamei has a high commercial value and is the primary cultured shellfish species globally. In this study, we have compared the hemolymph physiological responses between two L. vannamei strains under acute hypoxia. The results showed that hemocyanin concentration (HC) of strain A6410 was significantly higher than strain Zhengda; Total hemocyte counts (THC) decreased significantly in both strains under hypoxic stress (p < 0.05). We also investigated the temporal and spatial variations of hypoxia inducible factors 1 (HIF-1) by qRT-PCR. The results showed that hypoxia for 12 h increased the expression levels of HIF-1α in tissues of muscle and gill from the two strains (p < 0.05). In the hepatopancreas, the expression levels of HIF-1 increased significantly in strain Zhengda and decreased significantly in strain A6410 (p < 0.05). No significant changes of HIF-1 expression were detected in the same tissues between the two strains under hypoxia for 6 h (p > 0.05), but in the gills and hepatopancreas under hypoxia for 12 h (p < 0.05). Additionally, the expression level of HIF-1 was higher in the strain Zhengda than A6410 in the same tissue under hypoxia for 12 h. It was indicated that the hypoxic tolerance of Litopenaeus vannamei was closely correlated with the expression level of HIF-1, and the higher expression level of HIF-1 to hypoxia, the lower tolerance to hypoxia in the early stage of hypoxia. These results can help to better understand the molecular mechanisms of hypoxic tolerance and speed up the selective breeding process of hypoxia tolerance in L. vannamei. PMID:27016815

  20. Acute hypoxia increases the cerebral metabolic rate - a magnetic resonance imaging study.

    PubMed

    Vestergaard, Mark B; Lindberg, Ulrich; Aachmann-Andersen, Niels Jacob; Lisbjerg, Kristian; Christensen, Søren Just; Law, Ian; Rasmussen, Peter; Olsen, Niels V; Larsson, Henrik Bw

    2016-06-01

    The aim of the present study was to examine changes in cerebral metabolism by magnetic resonance imaging of healthy subjects during inhalation of 10% O2 hypoxic air. Hypoxic exposure elevates cerebral perfusion, but its effect on energy metabolism has been less investigated. Magnetic resonance imaging techniques were used to measure global cerebral blood flow and the venous oxygen saturation in the sagittal sinus. Global cerebral metabolic rate of oxygen was quantified from cerebral blood flow and arteriovenous oxygen saturation difference. Concentrations of lactate, glutamate, N-acetylaspartate, creatine and phosphocreatine were measured in the visual cortex by magnetic resonance spectroscopy. Twenty-three young healthy males were scanned for 60 min during normoxia, followed by 40 min of breathing hypoxic air. Inhalation of hypoxic air resulted in an increase in cerebral blood flow of 15.5% (p = 0.058), and an increase in cerebral metabolic rate of oxygen of 8.5% (p = 0.035). Cerebral lactate concentration increased by 180.3% ([Formula: see text]), glutamate increased by 4.7% ([Formula: see text]) and creatine and phosphocreatine decreased by 15.2% (p[Formula: see text]). The N-acetylaspartate concentration was unchanged (p = 0.36). In conclusion, acute hypoxia in healthy subjects increased perfusion and metabolic rate, which could represent an increase in neuronal activity. We conclude that marked changes in brain homeostasis occur in the healthy human brain during exposure to acute hypoxia. PMID:26661163

  1. Acute hypoxia increases the cerebral metabolic rate – a magnetic resonance imaging study

    PubMed Central

    Lindberg, Ulrich; Aachmann-Andersen, Niels Jacob; Lisbjerg, Kristian; Christensen, Søren Just; Law, Ian; Rasmussen, Peter; Olsen, Niels V; Larsson, Henrik BW

    2015-01-01

    The aim of the present study was to examine changes in cerebral metabolism by magnetic resonance imaging of healthy subjects during inhalation of 10% O2 hypoxic air. Hypoxic exposure elevates cerebral perfusion, but its effect on energy metabolism has been less investigated. Magnetic resonance imaging techniques were used to measure global cerebral blood flow and the venous oxygen saturation in the sagittal sinus. Global cerebral metabolic rate of oxygen was quantified from cerebral blood flow and arteriovenous oxygen saturation difference. Concentrations of lactate, glutamate, N-acetylaspartate, creatine and phosphocreatine were measured in the visual cortex by magnetic resonance spectroscopy. Twenty-three young healthy males were scanned for 60 min during normoxia, followed by 40 min of breathing hypoxic air. Inhalation of hypoxic air resulted in an increase in cerebral blood flow of 15.5% (p = 0.058), and an increase in cerebral metabolic rate of oxygen of 8.5% (p = 0.035). Cerebral lactate concentration increased by 180.3% (p<10-6), glutamate increased by 4.7% (p<10-4) and creatine and phosphocreatine decreased by 15.2% (p<10-3). The N-acetylaspartate concentration was unchanged (p = 0.36). In conclusion, acute hypoxia in healthy subjects increased perfusion and metabolic rate, which could represent an increase in neuronal activity. We conclude that marked changes in brain homeostasis occur in the healthy human brain during exposure to acute hypoxia. PMID:26661163

  2. Effect of carotid denervation on plasma vasopressin levels during acute hypoxia in the late-gestation sheep fetus.

    PubMed Central

    Giussani, D A; McGarrigle, H H; Spencer, J A; Moore, P J; Bennet, L; Hanson, M A

    1994-01-01

    1. We measured plasma concentrations of arginine vasopressin (AVP), arterial, venous and amniotic pressures, and carotid and femoral blood flows in fifteen chronically instrumented fetal sheep at 119-125 days of gestation. In eight of the fetuses the carotid sinus nerves were cut (denervated fetuses); the other seven remained intact and served as controls (intact fetuses). 2. In the intact fetuses during hypoxia there was an increase in plasma [AVP] and in perfusion (arterial-venous) pressure, a transient bradycardia, and an increase in carotid and a decrease in femoral blood flow. Whilst femoral vascular resistance (perfusion pressure/femoral blood flow) increased, there were no changes in carotid vascular resistance during hypoxia. 3. In the denervated fetuses no significant bradycardia, fall in femoral blood flow or increase in femoral vascular resistance was present soon after the onset of hypoxia but plasma AVP increased to similar concentrations to those observed in intact fetuses during hypoxia. 4. We conclude that carotid denervation does not affect plasma [AVP] during hypoxia in fetal sheep. This suggests that (1) AVP release during hypoxia is not mediated by a carotid chemoreflex and (2) AVP does not play an important role in these initial fetal cardiovascular responses. Furthermore, we previously reported that intact fetuses survive acute hypoxia better than denervated fetuses following phentolamine treatment, and we believe this to be due to the action of a non-alpha-adrenergic vasoconstrictor released in part via a carotid chemoreflex. The present results suggest that this vasoconstrictor is not AVP. PMID:8071890

  3. Cerebrovascular and ventilatory responses to acute isocapnic hypoxia in healthy aging and lung disease: effect of vitamin C.

    PubMed

    Hartmann, Sara E; Waltz, Xavier; Kissel, Christine K; Szabo, Lian; Walker, Brandie L; Leigh, Richard; Anderson, Todd J; Poulin, Marc J

    2015-08-15

    Acute hypoxia increases cerebral blood flow (CBF) and ventilation (V̇e). It is unknown if these responses are impacted with normal aging, or in patients with enhanced oxidative stress, such as (COPD). The purpose of the study was to 1) investigate the effects of aging and COPD on the cerebrovascular and ventilatory responses to acute hypoxia, and 2) to assess the effect of vitamin C on these responses during hypoxia. In 12 Younger, 14 Older, and 12 COPD, we measured peak cerebral blood flow velocity (V̄p; index of CBF), and V̇e during two 5-min periods of acute isocapnic hypoxia, under conditions of 1) saline-sham; and 2) intravenous vitamin C. Antioxidants [vitamin C, superoxide dismutase (SOD), glutathione peroxidase, and catalase], oxidative stress [malondialdehyde (MDA) and advanced protein oxidation product], and nitric oxide metabolism end products (NOx) were measured in plasma. Following the administration of vitamin C, vitamin C, SOD, catalase, and MDA increased, while NOx decreased. V̄p and V̇e sensitivity to hypoxia was reduced in Older by ∼60% (P < 0.02). COPD patients exhibited similar V̄p and V̇e responses to Older (P > 0.05). Vitamin C did not have an effect on the hypoxic V̇e response but selectively decreased the V̄p sensitivity in Younger only. These findings suggest a reduced integrative reflex (i.e., cerebrovascular and ventilatory) during acute hypoxemia in healthy older adults. Vitamin C does not appear to have a large influence on the cerebrovascular or ventilatory responses during acute hypoxia. PMID:26089546

  4. Severe hypoxia affects exercise performance independently of afferent feedback and peripheral fatigue.

    PubMed

    Millet, Guillaume Y; Muthalib, Makii; Jubeau, Marc; Laursen, Paul B; Nosaka, Kazunori

    2012-04-01

    To test the hypothesis that hypoxia centrally affects performance independently of afferent feedback and peripheral fatigue, we conducted two experiments under complete vascular occlusion of the exercising muscle under different systemic O(2) environmental conditions. In experiment 1, 12 subjects performed repeated submaximal isometric contractions of the elbow flexor to exhaustion (RCTE) with inspired O(2) fraction fixed at 9% (severe hypoxia, SevHyp), 14% (moderate hypoxia, ModHyp), 21% (normoxia, Norm), or 30% (hyperoxia, Hyper). The number of contractions (performance), muscle (biceps brachii), and prefrontal near-infrared spectroscopy (NIRS) parameters and high-frequency paired-pulse (PS100) evoked responses to electrical muscle stimulation were monitored. In experiment 2, 10 subjects performed another RCTE in SevHyp and Norm conditions in which the number of contractions, biceps brachii electromyography responses to electrical nerve stimulation (M wave), and transcranial magnetic stimulation responses (motor-evoked potentials, MEP, and cortical silent period, CSP) were recorded. Performance during RCTE was significantly reduced by 10-15% in SevHyp (arterial O(2) saturation, SpO(2) = ∼75%) compared with ModHyp (SpO(2) = ∼90%) or Norm/Hyper (SpO(2) > 97%). Performance reduction in SevHyp occurred despite similar 1) metabolic (muscle NIRS parameters) and functional (changes in PS100 and M wave) muscle states and 2) MEP and CSP responses, suggesting comparable corticospinal excitability and spinal and cortical inhibition between SevHyp and Norm. It is concluded that, in SevHyp, performance and central drive can be altered independently of afferent feedback and peripheral fatigue. It is concluded that submaximal performance in SevHyp is partly reduced by a mechanism related directly to brain oxygenation. PMID:22323647

  5. The effect of acute and chronic hypoxia on thoracic gas volume in anaesthetized rats.

    PubMed Central

    Barer, G R; Herget, J; Sloan, P J; Suggett, A J

    1978-01-01

    1. Thoracic gas volume at end expiration (functional residual capacity, FRC) was measured in chronically and acutely hypoxic anaesthetized rats by a plethysmograph method. 2. FRC, measured during air breathing, was 34-62% larger in rats which had been kept in an environmental chamber in 8, 10 or 12% O2 for 3 weeks than in littermate controls. FRC returned to normal after the rats had returned to air for 9 days. There was no constant difference in the pattern of breathing between control and chronically hypoxic rats. 3. Pressure-volume curves measured post mortem showed no difference in the volume of the lung at 25 cm H2O pressure or in the compliance of the lung between chronically hypoxic and control rats. Thus there was no gross mechanical change in the lung to account for the increase in FRC. 4. Acute hypoxia caused by breathing 12% O2 increased FRC in control but not in chronically hypoxic rats. The increase in FRC in control rats was abolished by combined blockade of the vagus nerves and carotid bodies (with procaine) but not by vagal blockade alone. 5. The combined vagal and carotid body blockade reduced FRC significantly in rats which had been in 10% O2 for 3 days but not in those which had been in 10% O2 for 21 days. 6. Lung area measured from radiographs was not reduced by a muscle relaxant in chronically hypoxic rats. Electromyograms from anterior intercostal muscles and the diaphragm showed no electrical activity in expiration in chronically hypoxic rats which might indicate an active muscular basis for their increased FRC. However when FRC was raised by acute hypoxia in control animals there was also no increase in electrical activity in expiration which could have explained their increase in lung volume. 7. We concluded that the increase in FRC during acute hypoxia in control rats was probably due to a reflex from the carotid body. The increase in FRC in chronically hypoxic rats, which was present while they breathed air, may have had an active

  6. Effects of copper, hypoxia and acute temperature shifts on mitochondrial oxidation in rainbow trout (Oncorhynchus mykiss) acclimated to warm temperature.

    PubMed

    Sappal, Ravinder; Fast, Mark; Stevens, Don; Kibenge, Fred; Siah, Ahmed; Kamunde, Collins

    2015-12-01

    Temperature fluctuations, hypoxia and metals pollution frequently occur simultaneously or sequentially in aquatic systems and their interactions may confound interpretation of their biological impacts. With a focus on energy homeostasis, the present study examined how warm acclimation influences the responses and interactions of acute temperature shift, hypoxia and copper (Cu) exposure in fish. Rainbow trout (Oncorhynchus mykiss) were acclimated to cold (11°C; control) and warm (20°C) temperature for 3 weeks followed by exposure to environmentally realistic levels of Cu and hypoxia for 24h. Subsequently, mitochondrial electron transport system (ETS) respiratory activity supported by complexes I-IV (CI-IV), plasma metabolites and condition indices were measured. Warm acclimation reduced fish condition, induced aerobic metabolism and altered the responses of fish to acute temperature shift, hypoxia and Cu. Whereas warm acclimation decelerated the ETS and increased the sensitivity of maximal oxidation rates of the proximal (CI and II) complexes to acute temperature shift, it reduced the thermal sensitivity of state 4 (proton leak). Effects of Cu with and without hypoxia were variable depending on the acclimation status and functional index. Notably, Cu stimulated respiratory activity in the proximal ETS segments, while hypoxia was mostly inhibitory and minimized the stimulatory effect of Cu. The effects of Cu and hypoxia were modified by temperature and showed reciprocal antagonistic interaction on the ETS and plasma metabolites, with modest additive actions limited to CII and IV state 4. Overall, our results indicate that warm acclimation came at a cost of reduced ETS efficiency and increased sensitivity to added stressors. PMID:26513222

  7. Xenon Combined with Therapeutic Hypothermia Is Not Neuroprotective after Severe Hypoxia-Ischemia in Neonatal Rats

    PubMed Central

    Sabir, Hemmen; Osredkar, Damjan; Maes, Elke; Wood, Thomas; Thoresen, Marianne

    2016-01-01

    Background Therapeutic hypothermia (TH) is standard treatment following perinatal asphyxia in newborn infants. Experimentally, TH is neuroprotective after moderate hypoxia-ischemia (HI) in seven-day-old (P7) rats. However, TH is not neuroprotective after severe HI. After a moderate HI insult in newborn brain injury models, the anesthetic gas xenon (Xe) doubles TH neuroprotection. The aim of this study was to examine whether combining Xe and TH is neuroprotective as applied in a P7 rat model of severe HI. Design/Methods 120 P7 rat pups underwent a severe HI insult; unilateral carotid artery ligation followed by hypoxia (8% O2 for 150min at experimental normothermia (NT-37: Trectal 37°C). Surviving pups were randomised to immediate NT-37 for 5h (n = 36), immediate TH-32: Trectal 32°C for 5h (n = 25) or immediate TH-32 plus 50% inhaled Xe for 5h (n = 24). Pups were sacrificed after one week of survival. Relative area loss of the ligated hemisphere was measured, and neurons in the subventricular zone of this injured hemisphere were counted, to quantify brain damage. Results Following the HI insult, median (interquartile range, IQR) hemispheric brain area loss was similar in all groups: 63.5% (55.5–75.0) for NT-37 group, 65.0% (57.0–65.0) for TH-32 group, and 66.5% (59.0–72.0) for TH-32+Xe50% group (not significant). Correspondingly, there was no difference in neuronal cell count (NeuN marker) in the subventricular zone across the three treatment groups. Conclusions Immediate therapeutic hypothermia with or without additional 50% inhaled Xe, does not provide neuroprotection one week after severe HI brain injury in the P7 neonatal rat. This model aims to mimic the clinical situation in severely asphyxiated neonates and treatment these newborns remains an ongoing challenge. PMID:27253085

  8. The Effects of Severe Hypoxia on Glycolytic Flux and Enzyme Activity in a Model of Solid Tumors.

    PubMed

    Smith, Hannah; Board, Mary; Pellagatti, Andrea; Turley, Helen; Boultwood, Jacqueline; Callaghan, Richard

    2016-08-01

    Solid tumors contend with, and adapt to, a hostile micro-environment that includes limited availability of nutrient fuels and oxygen. The presence of hypoxia (O2 <5%) stabilizes the transcription factor Hif1 and results in numerous cellular adaptations including increased flux of glucose through glycolysis. Increasingly, more sophisticated analysis of tumor oxygenation has revealed large gradients of oxygen tension and significant regions under severe hypoxia (O2 ∼0.1%). The present investigation has demonstrated a significant increase in the glycolytic flux rate when tumor spheroids were exposed to 0.1% O2 . The severe hypoxia was associated with uniform pimonidazole adduct formation and elevated levels of Hif1α and c-Myc. This resulted in elevated expression of GLUT and MCT transporters, in addition to increased activity of PFK1 in comparison to that observed in normoxia. However, the protein expression and enzymatic capacity of HK2, G6PDH, PK, and LDH were all reduced by severe hypoxia. Clearly, the effects of exposure to severe hypoxia lead to a significantly abridged Hif1 response, yet one still able to elevate glycolytic flux and prevent loss of intermediates to anabolism. J. Cell. Biochem. 117: 1890-1901, 2016. © 2016 Wiley Periodicals, Inc. PMID:26755257

  9. Severe Blunt Muscle Trauma in Rats: Only Marginal Hypoxia in the Injured Area

    PubMed Central

    Funk, Kristina; Scheerer, Nina; Verhaegh, Rabea; Pütter, Carolin; Fandrey, Joachim; de Groot, Herbert

    2014-01-01

    Background After severe muscle trauma, hypoxia due to microvascular perfusion failure is generally believed to further increase local injury and to impair healing. However, detailed analysis of hypoxia at the cellular level is missing. Therefore, in the present work, spectroscopic measurements of microvascular blood flow and O2 supply were combined with immunological detection of hypoxic cells to estimate O2 conditions within the injured muscle area. Materials and Methods Severe blunt muscle trauma was induced in the right Musculus gastrocnemius of male Wistar rats by a standardized “weight-drop” device. Microvascular blood flow, relative hemoglobin amount, and hemoglobin O2 saturation were determined by laser Doppler and white-light spectroscopy. Hypoxic cells were detected by histologic evaluation of covalent binding of pimonidazole and expression of HIF-1α. Results Directly after trauma and until the end of experiment (480 minutes), microvascular blood flow and relative hemoglobin amount were clearly increased. In contrast to blood flow and relative hemoglobin amount, there was no immediate but a delayed increase of microvascular hemoglobin O2 saturation. Pimonidazole immunostaining revealed a hypoxic fraction (percentage area of pimonidazole-labelled muscle cells within the injured area) between 8 to 3%. There was almost no HIF-1α expression detectable in the muscle cells under each condition studied. Conclusions In the early phase (up to 8 hours) after severe blunt muscle trauma, the overall microvascular perfusion of the injured area and thus its O2 supply is clearly increased. This increased O2 supply is obviously sufficient to ensure normoxic (or even hyperoxic) conditions in the vast majority of the cells. PMID:25360779

  10. Effects of hypoxia on muscle protein synthesis and anabolic signaling at rest and in response to acute resistance exercise.

    PubMed

    Etheridge, Timothy; Atherton, Philip J; Wilkinson, Daniel; Selby, Anna; Rankin, Debbie; Webborn, Nick; Smith, Kenneth; Watt, Peter W

    2011-10-01

    Chronic reductions in tissue O(2) tension (hypoxia) are associated with muscle atrophy and blunted hypertrophic responses to resistance exercise (RE) training. However, the effect of hypoxia on muscle protein synthesis (MPS) at rest and after RE is unknown. In a crossover study, seven healthy men (21.4 ± 0.7 yr) performed unilateral leg RE (6 × 8 repetitions at 70% 1-repetition maximum) under normoxic (20.9% inspired O(2)) and normobaric hypoxic (12% inspired O(2) for 3.5 h) postabsorptive conditions. Immediately after RE the rested leg was biopsied, and a primed continuous infusion of [1,2-(13)C(2)]leucine was maintained for 2.5 h before final biopsies from both legs to measure tracer incorporation and signaling responses (i.e., ribosomal S6 kinase 1). After 3.5 h of hypoxia, MPS was not different from normoxia in the rested leg (normoxia 0.033 ± 0.016 vs. hypoxia 0.043 ± 0.016%/h). MPS increased significantly from baseline 2.5 h after RE in normoxia (0.033 ± 0.016 vs. 0.104 ± 0.038%/h) but not hypoxia (0.043 ± 0.016 vs. 0.060 ± 0.063%/h). A significant linear relationship existed between MPS 2.5 h after RE in hypoxia and mean arterial blood O(2) saturation during hypoxia (r(2) = 0.49, P = 0.04). Phosphorylation of p70S6K(Thr389) remained unchanged in hypoxia at rest but increased after RE in both normoxia and hypoxia (2.6 ± 1.2-fold and 3.4 ± 1.1-fold, respectively). Concentrations of the hypoxia-responsive mTOR inhibitor regulated in development and DNA damage-1 were unaltered by hypoxia or RE. We conclude that normobaric hypoxia does not reduce MPS over 3.5 h at rest but blunts the increased MPS response to acute RE to a degree dependent on extant SpO(2). PMID:21750270

  11. [The role of adenosine Al receptors and mitochondrial K+ATP channels in the mechanism of increasing the resistance to acute hypoxia in the combined effects of hypoxia and hypercapnia].

    PubMed

    Tregub, P P; Kulikov, V P; Stepanova, L A; Zabrodina, A S; Nagibaeva, M E

    2014-01-01

    We studied the role of the role of mitoK+ATp channels and Al-adenosine receptor in the mechanism of increasing the resistance to acute hypoxia after hypoxic, hypercapnic and hypercapnic-hypoxic preconditioning. It is shown that mitochondrial ATP-sensitive potassium channels and Al-adenosine receptors, an important mechanism of preconditioning have a high value to increase the resistance to acute hypoxia/ischemia in the combined effect of hypoxia and hypercapnia. However, with regard to the adenosine receptor, this mechanism is realized without the participation hypercapnic component, which apparently starts neuroprotection without activation of the adenosine Al receptors. PMID:25980226

  12. Antibiotics as part of the management of severe acute malnutrition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Severe acute malnutrition contributes to 1 million deaths among children annually. Adding routine antibiotic agents to nutritional therapy may increase recovery rates and decrease mortality among children with severe acute malnutrition treated in the community. In this randomized, double-blind, plac...

  13. THE PANC 3 SCORE PREDICTING SEVERITY OF ACUTE PANCREATITIS

    PubMed Central

    BEDUSCHI, Murilo Gamba; MELLO, André Luiz Parizi; VON-MÜHLEN, Bruno; FRANZON, Orli

    2016-01-01

    Background : About 20% of cases of acute pancreatitis progress to a severe form, leading to high mortality rates. Several studies suggested methods to identify patients that will progress more severely. However, most studies present problems when used on daily practice. Objective : To assess the efficacy of the PANC 3 score to predict acute pancreatitis severity and its relation to clinical outcome. Methods : Acute pancreatitis patients were assessed as to sex, age, body mass index (BMI), etiology of pancreatitis, intensive care need, length of stay, length of stay in intensive care unit and mortality. The PANC 3 score was determined within the first 24 hours after diagnosis and compared to acute pancreatitis grade of the Revised Atlanta classification. Results : Out of 64 patients diagnosed with acute pancreatitis, 58 met the inclusion criteria. The PANC 3 score was positive in five cases (8.6%), pancreatitis progressed to a severe form in 10 cases (17.2%) and five patients (8.6%) died. Patients with a positive score and severe pancreatitis required intensive care more often, and stayed for a longer period in intensive care units. The PANC 3 score showed sensitivity of 50%, specificity of 100%, accuracy of 91.4%, positive predictive value of 100% and negative predictive value of 90.6% in prediction of severe acute pancreatitis. Conclusion : The PANC 3 score is useful to assess acute pancreatitis because it is easy and quick to use, has high specificity, high accuracy and high predictive value in prediction of severe acute pancreatitis. PMID:27120730

  14. Nitric oxide associated with iNOS expression inhibits acetylcholinesterase activity and induces memory impairment during acute hypobaric hypoxia.

    PubMed

    Udayabanu, M; Kumaran, D; Nair, R Unnikrishnan; Srinivas, P; Bhagat, Neeta; Aneja, R; Katyal, Anju

    2008-09-16

    The mechanisms responsible for cholinergic dysfunction associated learning and memory impairment during hypoxia are not well-understood. However it is known that inflammatory mediators like inducible nitric oxide synthase (iNOS) hamper the functions of cholinergic neurons. In this present experiment we made an effort to study the iNOS expression mediated retrograde and anterograde memory impairment in Balb/c mice following acute hypobaric hypoxia (at an altitude of 23,000ft for 6h) using elevated plus maze and passive avoidance step-through tasks. Our results demonstrated that hypoxia transiently impairs the retrograde memory without affecting the anterograde memory functions, accompanied with a substantial rise in iNOS expression and nitric oxide levels in cerebral cortex on days 2 and 3 post hypoxia. Treatment with aminoguanidine (iNOS inhibitor ), resulted in down-regulation of the iNOS expression, attenuation of the surge of nitric oxide (NO) in cerebral cortex and reversal of retrograde memory impairment due to hypoxia. Moreover the reduced AChE activity and elevated lipid peroxidation in cerebral cortex were evident during post hypoxia re-oxygenation period, which was not observed in the hippocampus. Additionally, NO donor spermine NONOate could inhibit the AChE activity in brain homogenates in a concentration-dependent manner, which further substantiate that nitric oxide produced during post hypoxia re-oxygenation, primarily contributes to the observed inhibition of cortical AChE activity. Based on these experiments we hypothesize that the NO burst as a result of iNOS upregulation during hypoxia interrupts the memory consolidation by altering the cholinergic functions. PMID:18639532

  15. Potential role of the glycolytic oscillator in acute hypoxia in tumors.

    PubMed

    Fru, Leonard Che; Adamson, Erin B; Campos, David D; Fain, Sean B; Jacques, Steven L; van der Kogel, Albert J; Nickel, Kwang P; Song, Chihwa; Kimple, Randall J; Kissick, Michael W

    2015-12-21

    Tumor acute hypoxia has a dynamic component that is also, at least partially, coherent. Using blood oxygen level dependent magnetic resonance imaging, we observed coherent oscillations in hemoglobin saturation dynamics in cell line xenograft models of head and neck squamous cell carcinoma. We posit a well-established biochemical nonlinear oscillatory mechanism called the glycolytic oscillator as a potential cause of the coherent oscillations in tumors. These data suggest that metabolic changes within individual tumor cells may affect the local tumor microenvironment including oxygen availability and therefore radiosensitivity. These individual cells can synchronize the oscillations in patches of similar intermediate glucose levels. These alterations have potentially important implications for radiation therapy and are a potential target for optimizing the cancer response to radiation. PMID:26576743

  16. Cardiopulmonary responses to acute hypoxia, head-down tilt and fluid loading in anesthetized dogs

    NASA Technical Reports Server (NTRS)

    Loeppky, J. A.; Scotto, P.; Riedel, C.; Avasthi, P.; Koshukosky, V.; Chick, T. W.

    1991-01-01

    Cardiopulmonary responses to acute hypoxia (HY), fluid loading by saline infusion (FL), and head-down tilt (HD) of mechanically ventilated anesthetized dogs were investigated by measuring thermodynamics and pulmonary gas exchange. It was found that HD decreased the total respiratory compliance both during HY and normoxia (NO) and that the reduction in compliance by FL was twice as large as by HD. Superimposing HD on HY doubled the increase in vascular resistance due to HY alone. In the systemic circulation, HD lowered the resistance to below NO levels. There was a significant positive correlation between the changes in blood volume and in pulmonary artery pressure for experimental transitions, suggesting that a shift in blood volume from systemic to pulmonary circulations and changes in the total blood volume may contribute substantially to these apparent changes in resistance.

  17. Potential role of the glycolytic oscillator in acute hypoxia in tumors

    NASA Astrophysics Data System (ADS)

    Che Fru, Leonard; Adamson, Erin B.; Campos, David D.; Fain, Sean B.; Jacques, Steven L.; van der Kogel, Albert J.; Nickel, Kwang P.; Song, Chihwa; Kimple, Randall J.; Kissick, Michael W.

    2015-12-01

    Tumor acute hypoxia has a dynamic component that is also, at least partially, coherent. Using blood oxygen level dependent magnetic resonance imaging, we observed coherent oscillations in hemoglobin saturation dynamics in cell line xenograft models of head and neck squamous cell carcinoma. We posit a well-established biochemical nonlinear oscillatory mechanism called the glycolytic oscillator as a potential cause of the coherent oscillations in tumors. These data suggest that metabolic changes within individual tumor cells may affect the local tumor microenvironment including oxygen availability and therefore radiosensitivity. These individual cells can synchronize the oscillations in patches of similar intermediate glucose levels. These alterations have potentially important implications for radiation therapy and are a potential target for optimizing the cancer response to radiation.

  18. [Effect of tricarboxylic acid cycle intermediates on nitric oxide system during acute hypoxia].

    PubMed

    Kurhaliuk, N M

    2002-01-01

    Effects Crebs Cycle of exogenous intermediates sodium succinate (50 mg/kg) and sodium alpha-ketoglutarate (200 mg/kg) on processes of mitochondrial ADP-stimulated respiration (using as substrates of oxidation 0.35 mM succinate, 1 mM alpha-ketoglutarate), production of nitric oxide under NO2-, NO3-, as well as carbamide, putrescyne content and processes of lipid peroxidation in the rats liver under acute hypoxia (7% O2 in N2, 30 min) have been studied. It was shown, that the exogenous sodium alpha-ketoglutarate increases nitric oxide content, aminotransferase activation, inhibition of succinatedehydrogenase simultaneously more than exogenous sodium succinate. It correlates with decreasing of processes lipid peroxidation in liver. PMID:14964867

  19. Effect of Acute Hypoxia on Post-Exercise Parasympathetic Reactivation in Healthy Men

    PubMed Central

    Al Haddad, Hani; Mendez-Villanueva, Alberto; Bourdon, Pitre C.; Buchheit, Martin

    2012-01-01

    In this study we assessed the effect of acute hypoxia on post-exercise parasympathetic reactivation inferred from heart rate (HR) recovery (HRR) and HR variability (HRV) indices. Ten healthy males participated in this study. Following 10 min of seated rest, participants performed 5 min of submaximal running at the speed associated with the first ventilatory threshold (Sub) followed by a 20-s all-out supramaximal sprint (Supra). Both Sub and Supra runs were immediately followed by 15 min of seated passive recovery. The resting and exercise sequence were performed in both normoxia (N) and normobaric hypoxia (H; FiO2 = 15.4%). HRR indices (e.g., heart beats recovered in the first minute after exercise cessation, HRR60s) and vagal-related HRV indices [i.e., natural logarithm of the square root of the mean of the sum of the squared differences between adjacent normal R–R intervals (Ln rMSSD)] were calculated for both conditions. Difference in the changes between N and H for all HR-derived indices were also calculated for both Sub and Supra. HRR60s was greater in N compared with H following Sub only (60 ± 14 vs. 52 ± 19 beats min−1, P = 0.016). Ln rMSSD was greater in N compared with H (post Sub: 3.60 ± 0.45 vs. 3.28 ± 0.44 ms in N and H, respectively, and post Supra: 2.66 ± 0.54 vs. 2.65 ± 0.63 ms, main condition effect P = 0.02). When comparing the difference in the changes, hypoxia decreased HRR60s (−14.3% ± 17.2 vs. 5.2% ± 19.3; following Sub and Supra, respectively; P = 0.03) and Ln rMSSD (−8.6% ± 7.0 vs. 2.0% ± 13.3, following Sub and Supra, respectively; P = 0.08, Cohen’s effect size = 0.62) more following Sub than Supra. While hypoxia may delay parasympathetic reactivation following submaximal exercise, its effect is not apparent following supramaximal exercise. This may suggest that the effect of blood O2 partial pressure on parasympathetic reactivation is limited

  20. Nicotinamide and pentoxifylline increase human leucocyte filterability: a possible mechanism for reduction of acute hypoxia.

    PubMed Central

    Honess, D. J.; Kitamoto, Y.; Rampling, M. R.; Bleehen, N. M.

    1996-01-01

    Transient plugging of microcapillaries by leucocytes is a possible reason for the occurrence of acute hypoxia in tumours. We compared the abilities of nicotinamide at 1000 micrograms ml-1 and 150 micrograms ml-1 and pentoxifylline at 300 micrograms ml-1 to increase the filterability of normal and artificially activated human leucocytes through 8 microns pores, as a model for the capillary bed. Using a St George's filtrometer, filterability of treated leucocyte suspensions was compared with control for three to six sequential 60 microliters samples, normalising control values to unity. Pentoxifylline at 300 micrograms ml-1 halved the ratio of treated to control value to 0.47 +/- 0.13 (2 s.e.), P = 0.001 (i.e. an increase in filterability), and nicotinamide at 1000 micrograms ml-1 reduced it to 0.69 +/- 0.22, P = 0.04, but the clinically achievable 150 micrograms ml-1 was ineffective (0.82 +/- 0.25, P = 0.24). Filterability of artificially activated leucocytes was reduced (3.9 +/- 1.20) but was restored to control values of unity by 1000 micrograms ml-1 nicotinamide and 300 micrograms ml-1 pentoxifylline and partially restored by 150 micrograms ml-1 nicotinamide (1.2 mM), which was isoeffective with 100 micrograms ml-1 pentoxifylline (0.37 mM). Pentoxifylline is therefore more effective on a molar basis and was shown to affect both polymorphonuclear leucocytes and lymphocytes, while nicotinamide only affects lymphocytes. The data are consistent with the hypothesis that both agents modify acute hypoxia by increasing leucocyte filterability. PMID:8763888

  1. A Year in Hypoxia: Epibenthic Community Responses to Severe Oxygen Deficit at a Subsea Observatory in a Coastal Inlet

    PubMed Central

    Matabos, Marjolaine; Tunnicliffe, Verena; Juniper, S. Kim; Dean, Courtney

    2012-01-01

    Changes in ocean ventilation driven by climate change result in loss of oxygen in the open ocean that, in turn, affects coastal areas in upwelling zones such as the northeast Pacific. Saanich Inlet, on the west coast of Canada, is a natural seasonally hypoxic fjord where certain continental shelf species occur in extreme hypoxia. One study site on the VENUS cabled subsea network is located in the hypoxic zone at 104 m depth. Photographs of the same 5 m2 area were taken with a remotely-controlled still camera every 2/3 days between October 6th 2009 and October 18th 2010 and examined for community composition, species behaviour and microbial mat features. Instruments located on a near-by platform provided high-resolution measurements of environmental variables. We applied multivariate ordination methods and a principal coordinate analysis of neighbour matrices to determine temporal structures in our dataset. Responses to seasonal hypoxia (0.1–1.27 ml/l) and its high variability on short time-scale (hours) varied among species, and their life stages. During extreme hypoxia, microbial mats developed then disappeared as a hippolytid shrimp, Spirontocaris sica, appeared in high densities (200 m−2) despite oxygen below 0.2 ml/l. The slender sole Lyopsetta exilis was abundant in severe hypoxia and diminished as oxygen increased in the summer. This planktivore may be responding to changes in the depth of the diurnal migration of zooplankton. While the squat lobster Munida quadrispina was common at all times, juveniles disappeared in fluctuating conditions. Despite low oxygen conditions, animal densities were high indicating that the risk from hypoxia is balanced by factors such as food availability and escape from less tolerant predators. As hypoxia increases on the continental shelf, we expect benthic communities to become dominated by low diversity, hypoxia-tolerant species of low commercial significance. PMID:23029145

  2. [An oneiroid experience during severe acute polyradiculoneuritis].

    PubMed

    Wegener, K; Tassan, P; Josse, M O; Bolgert, F

    1995-02-01

    This study is to present a psychopathological analysis of complex hallucinatory symptoms--without consciousness breaking up in confusional state--occurring in patients with acute Guillain-Barré's syndrome diagnosis requiring neurological intensive care. Finally the patients experience an unitary and closed situation "close to dream without being dream". This experience is corresponding to the semeiology of the "oneiroid experience" (Mayer-Gross, 1924). The "oneiroid experience" appears to be of syndromic nature independent of any etiological and/or nosological classification. But its conceptualization does probably need widening: the oneiroid world appears to be a creation of a primitive function which inserts us in the world before any science or verification. PMID:7741405

  3. Different cyclical intermittent hypoxia severities have different effects on hippocampal microvasculature.

    PubMed

    Lim, Diane C; Brady, Daniel C; Soans, Rajath; Kim, Emily Y; Valverde, Laise; Keenan, Brendan T; Guo, Xiaofeng; Kim, Woo Young; Park, Min Jeong; Galante, Raymond; Shackleford, James A; Pack, Allan I

    2016-07-01

    Recent studies have shown an association between obstructive sleep apnea (OSA) and cognitive impairment. This study was done to investigate whether varied levels of cyclical intermittent hypoxia (CIH) differentially affect the microvasculature in the hippocampus, operating as a mechanistic link between OSA and cognitive impairment. We exposed C57BL/6 mice to sham [continuous air, arterial O2 saturation (SaO2 ) 97%], severe CIH to inspired O2 fraction (FiO2 ) = 0.10 (CIH10; SaO2 nadir of 61%), or very severe CIH to FiO2 = 0.05 (CIH5; SaO2 nadir of 37%) for 12 h/day for 2 wk. We quantified capillary length using neurostereology techniques in the dorsal hippocampus and utilized quantitative PCR methods to measure changes in sets of genes related to angiogenesis and to metabolism. Next, we employed immunohistochemistry semiquantification algorithms to quantitate GLUT1 protein on endothelial cells within hippocampal capillaries. Capillary length differed among CIH severity groups (P = 0.013) and demonstrated a linear relationship with CIH severity (P = 0.002). There was a strong association between CIH severity and changes in mRNA for VEGFA (P < 0.0001). Less strong, but nominally significant associations with CIH severity were also observed for ANGPT2 (PANOVA = 0.065, PTREND = 0.040), VEGFR2 (PANOVA = 0.032, PTREND = 0.429), and TIE-2 (PANOVA = 0.006, PTREND = 0.010). We found that the CIH5 group had increased GLUT1 protein relative to sham (P = 0.006) and CIH10 (P = 0.001). There was variation in GLUT1 protein along the microvasculature in different hippocampal subregions. An effect of CIH5 on GLUT1 mRNA was seen (PANOVA = 0.042, PTREND = 0.012). Thus CIH affects the microvasculature in the hippocampus, but consequences depend on CIH severity. PMID:27125850

  4. Effect of Acute Dietary Nitrate Consumption on Oxygen Consumption During Submaximal Exercise in Hypobaric Hypoxia.

    PubMed

    Carriker, Colin R; Mermier, Christine M; Van Dusseldorp, Trisha A; Johnson, Kelly E; Beltz, Nicholas M; Vaughan, Roger A; McCormick, James J; Cole, Nathan H; Witt, Christopher C; Gibson, Ann L

    2016-08-01

    Reduced partial pressure of oxygen impairs exercise performance at altitude. Acute nitrate supplementation, at sea level, may reduce oxygen cost during submaximal exercise in hypobaric hypoxia. Therefore, we investigated the metabolic response during exercise at altitude following acute nitrate consumption. Ten well-trained (61.0 ± 7.4 ml/kg/min) males (age 28 ± 7 yr) completed 3 experimental trials (T1, T2, T3). T1 included baseline demographics, a maximal aerobic capacity test (VO2max) and five submaximal intensity cycling determination bouts at an elevation of 1600 m. A 4-day dietary washout, minimizing consumption of nitrate-rich foods, preceded T2 and T3. In a randomized, double-blind, placebo-controlled, crossover fashion, subjects consumed either a nitrate-depleted beetroot juice (PL) or ~12.8 mmol nitrate rich (NR) beverage 2.5 hr before T2 and T3. Exercise at 3500 m (T2 and T3) via hypobaric hypoxia consisted of a 5-min warm-up (25% of normobaric VO2max) and four 5-min cycling bouts (40, 50, 60, 70% of normobaric VO2max) each separated by a 4-min rest period. Cycling RPM and watts for each submaximal bout during T2 and T3 were determined during T1. Preexercise plasma nitrite was elevated following NR consumption compared with PL (1.4 ± 1.2 and 0.7 ± 0.3 uM respectively; p < .05). There was no difference in oxygen consumption (-0.5 ± 1.8, 0.1 ± 1.7, 0.7 ± 2.1, and 1.0 ± 3.0 ml/kg/min) at any intensity (40, 50, 60, 70% of VO2max, respectively) between NR and PL. Further, respiratory exchange ratio, oxygen saturation, heart rate and rating of perceived exertion were not different at any submaximal intensity between NR and PL either. Blood lactate, however, was reduced following NR consumption compared with PL at 40 and 60% of VO2max (p < .0.05). Our findings suggest that acute nitrate supplementation before exercise at 3500 m does not reduce oxygen cost but may reduce blood lactate accumulation at lower intensity workloads. PMID:26630309

  5. Determinants of frequency long-term facilitation following acute intermittent hypoxia in vagotomized rats.

    PubMed

    Baker-Herman, Tracy L; Mitchell, Gordon S

    2008-06-30

    Acute intermittent (AIH), but not acute sustained hypoxia (ASH) elicits a form of respiratory plasticity known as long-term facilitation (LTF). In anesthetized rats, LTF is expressed as increased respiratory-related nerve burst amplitude, with variable effects on burst frequency. We analyzed a large data set from multiple investigators using the same experimental protocol to determine factors influencing frequency LTF. Our meta-analysis revealed that AIH elicits both phrenic amplitude and frequency LTF in anesthetized and vagotomized rats, but frequency LTF is small in comparison with amplitude LTF (12% versus 60%, respectively). ASH elicits a small, but significant frequency and amplitude LTF (8% and 10%, respectively) that is not significantly different than controls. Similar to all published reports, analysis of this large data set confirms that phrenic amplitude LTF following AIH is significantly greater than ASH. Multiple regression analysis revealed a strong correlation between baseline burst frequency and frequency LTF. Variations in baseline burst frequency may contribute to variation in frequency LTF and may underlie the apparent effects of some drug treatments. PMID:18450525

  6. LIPOPOLYSACCHARIDE ATTENUATES PHRENIC LONG-TERM FACILITATION FOLLOWING ACUTE INTERMITTENT HYPOXIA

    PubMed Central

    Vinit, Stéphane; Windelborn, James A.; Mitchell, Gordon S.

    2011-01-01

    Lipopolysaccharide (LPS) induces inflammatory responses, including microglial activation in the central nervous system. Since LPS impairs certain forms of hippocampal and spinal neuroplasticity, we hypothesized that LPS would impair phrenic long-term facilitation (pLTF) following acute intermittent hypoxia (AIH) in outbred Sprague-Dawley (SD) and inbred Lewis (L) rats.. Approximately three hours following a single LPS injection (i.p.), the phrenic response during hypoxic episodes is reduced in both rat strains versus vehicle treated, control rats (SD: 84±7% vs. 128±14% baseline for control, p<0.05; L: 62±10% vs. 90±9% baseline for control, p<0.05). At 60 min post-AIH, pLTF is also diminished by LPS in both strains: (SD: 22±5% vs. 73.5±14% baseline for control, p<0.05; L: 18±15% vs. 56±8% baseline for control, p<0.05). LPS alone does not affect phrenic burst frequency in either rat strain, suggesting that acute LPS injection has minimal effect on brainstem respiratory rhythm generation. Thus, systemic LPS injections and (presumptive) inflammation impair pLTF, a form of spinal neuroplasticity in respiratory motor control. These results suggest that ongoing infection or inflammation must be carefully considered in studies of respiratory plasticity, or during attempts to harness spinal plasticity as a therapeutic tool in the treatment of respiratory insufficiency, such as spinal cord injury. PMID:21334467

  7. Determinants of frequency long-term facilitation following acute intermittent hypoxia in vagotomized rats

    PubMed Central

    Baker-Herman, Tracy L.; Mitchell, Gordon S.

    2008-01-01

    Acute intermittent (AIH), but not acute sustained hypoxia (ASH) elicits a form of respiratory plasticity known as long-term facilitation (LTF). In anesthetized rats, LTF is expressed as increased respiratory-related nerve burst amplitude, with variable effects on burst frequency. We analyzed a large data set from multiple investigators using the same experimental protocol to determine factors influencing frequency LTF. Our meta-analysis revealed that AIH elicits both phrenic amplitude and frequency LTF in anesthetized and vagotomized rats, but frequency LTF is small in comparison with amplitude LTF (12% versus 60%, respectively). ASH elicits a small, but significant frequency and amplitude LTF (8% and 10%, respectively) that is not significantly different than controls. Similar to all published reports, analysis of this large data set confirms that phrenic amplitude LTF following AIH is significantly greater than ASH. Multiple regression analysis revealed a strong correlation between baseline burst frequency and frequency LTF. Variations in baseline burst frequency may contribute to variation in frequency LTF and may underlie the apparent effects of some drug treatments. PMID:18450525

  8. Influence of acute normobaric hypoxia on physiological variables and lactate turn point determination in trained men.

    PubMed

    Ofner, Michael; Wonisch, Manfred; Frei, Mario; Tschakert, Gerhard; Domej, Wolfgang; Kröpfl, Julia M; Hofmann, Peter

    2014-12-01

    The goal of this study is to evaluate the response of physiological variables to acute normobaric hypoxia compared to normoxia and its influence on the lactate turn point determination according to the three-phase model of energy supply (Phase I: metabolically balanced at muscular level; Phase II: metabolically balanced at systemic level; Phase III: not metabolically balanced) during maximal incremental exercise. Ten physically active (VO2max 3.9 [0.49] l·min(-1)), healthy men (mean age [SD]: 25.3 [4.6] yrs.), participated in the study. All participants performed two maximal cycle ergometric exercise tests under normoxic as well as hypoxic conditions (FiO2 = 14%). Blood lactate concentration, heart rate, gas exchange data, and power output at maximum and the first and the second lactate turn point (LTP1, LTP2), the heart rate turn point (HRTP) and the first and the second ventilatory turn point (VETP1, VETP2) were determined. Since in normobaric hypoxia absolute power output (P) was reduced at all reference points (max: 314 / 274 W; LTP2: 218 / 184 W; LTP1: 110 / 96 W), as well as VO2max (max: 3.90 / 3.23 l·min(-1); LTP2: 2.90 / 2.43 l·min(-1); LTP1: 1.66 / 1.52 l·min(-1)), percentages of Pmax at LTP1, LTP2, HRTP and VETP1, VETP2 were almost identical for hypoxic as well as normoxic conditions. Heart rate was significantly reduced at Pmax in hypoxia (max: 190 / 185 bpm), but no significant differences were found at submaximal control points. Blood lactate concentration was not different at maximum, and all reference points in both conditions. Respiratory exchange ratio (RER) (max: 1.28 / 1.08; LTP2: 1.13 / 0.98) and ventilatory equivalents for O2 (max: 43.4 / 34.0; LTP2: 32.1 / 25.4) and CO2 (max: 34.1 / 31.6; LTP2: 29.1 / 26.1) were significantly higher at some reference points in hypoxia. Significant correlations were found between LTP1 and VETP1 (r = 0.778; p < 0.01), LTP2 and HRTP (r = 0.828; p < 0.01) and VETP2 (r = 0.948; p < 0.01) for power output for

  9. Increased eicosanoid levels in the Sugen/chronic hypoxia model of severe pulmonary hypertension.

    PubMed

    Al-Husseini, Aysar; Wijesinghe, Dayanjan S; Farkas, Laszlo; Kraskauskas, Donatas; Drake, Jennifer I; Van Tassel, Ben; Abbate, Antonio; Chalfant, Charles E; Voelkel, Norbert F

    2015-01-01

    Inflammation and altered immunity are recognized components of severe pulmonary arterial hypertension in human patients and in animal models of PAH. While eicosanoid metabolites of cyclooxygenase and lipoxygenase pathways have been identified in the lungs from pulmonary hypertensive animals their role in the pathogenesis of severe angioobliterative PAH has not been examined. Here we investigated whether a cyclooxygenase-2 (COX-2) inhibitor or diethylcarbamazine (DEC), that is known for its 5-lipoxygenase inhibiting and antioxidant actions, modify the development of PAH in the Sugen 5416/hypoxia (SuHx) rat model. The COX-2 inhibitor SC-58125 had little effect on the right ventricular pressure and did not prevent the development of pulmonary angioobliteration. In contrast, DEC blunted the muscularization of pulmonary arterioles and reduced the number of fully obliterated lung vessels. DEC treatment of SuHx rats, after the lung vascular disease had been established, reduced the degree of PAH, the number of obliterated arterioles and the degree of perivascular inflammation. We conclude that the non-specific anti-inflammatory drug DEC affects developing PAH and is partially effective once angioobliterative PAH has been established. PMID:25785937

  10. Increased Eicosanoid Levels in the Sugen/Chronic Hypoxia Model of Severe Pulmonary Hypertension

    PubMed Central

    Al-Husseini, Aysar; Wijesinghe, Dayanjan S.; Farkas, Laszlo; Kraskauskas, Donatas; Drake, Jennifer I.; Van Tassel, Ben; Abbate, Antonio; Chalfant, Charles E.; Voelkel, Norbert F.

    2015-01-01

    Inflammation and altered immunity are recognized components of severe pulmonary arterial hypertension in human patients and in animal models of PAH. While eicosanoid metabolites of cyclooxygenase and lipoxygenase pathways have been identified in the lungs from pulmonary hypertensive animals their role in the pathogenesis of severe angioobliterative PAH has not been examined. Here we investigated whether a cyclooxygenase-2 (COX-2) inhibitor or diethylcarbamazine (DEC), that is known for its 5-lipoxygenase inhibiting and antioxidant actions, modify the development of PAH in the Sugen 5416/hypoxia (SuHx) rat model. The COX-2 inhibitor SC-58125 had little effect on the right ventricular pressure and did not prevent the development of pulmonary angioobliteration. In contrast, DEC blunted the muscularization of pulmonary arterioles and reduced the number of fully obliterated lung vessels. DEC treatment of SuHx rats, after the lung vascular disease had been established, reduced the degree of PAH, the number of obliterated arterioles and the degree of perivascular inflammation. We conclude that the non-specific anti-inflammatory drug DEC affects developing PAH and is partially effective once angioobliterative PAH has been established. PMID:25785937

  11. Survival from acute renal failure after severe burns.

    PubMed

    Sawada, Y; Momma, S; Takamizawa, A; Nishida, S

    1984-12-01

    We describe a patient with 50 per cent, third degree flame burns who had a history of paint thinner inhalation for over 10 years. Moreover, chlorpromazine had been administered for the treatment of insomnia caused by chronic thinner intoxication. He developed oliguric acute renal failure soon after the burn injury, although adequate resuscitation therapy was given, and survived following frequent haemodialysis. Although survival from acute renal failure after severe burns is rare, once the diagnosis of acute renal failure has been made, haemodialysis should be instituted as early as possible. Furthermore, in a severely burnt patient with episodes of chronic and acute intoxication from organic chemicals or drugs which may have caused renal damage, acute renal failure may occur, so that careful observation is advised. PMID:6525538

  12. [PREVENTION AND CORRECTION OF PULMONARY COMPLICATIONS FOR SEVERE ACUTE PANCREATITIS].

    PubMed

    Fedorkiv, M B

    2015-06-01

    Increased of proinflammatory cytokines levels, including interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) on severe acute pancreatitis causes vasodilatation, increased permeability of the wall, accumulation of fluid in lung tissue and pleural sinuses. Transudate from acute parapancreatyc clusters of hot liquid and abdomen falls into the chest cavity through microscopic defects in the diaphragm due to the formation of pathological pleural-peritoneal connections or the relevant pressure gradient between the abdominal and pleural cavities. Remediation and removal of acute parapancreatyc clusters combined with the use of a multicomponent drug infusion therapy Cytoflavin provide a reduction in the frequency of pulmonary complications of acute pancreatitis from 48.3 to 31.0%. Use of the drug Cytoflavin reduces the severity of endogenous intoxication and mortality from acute lung injury from 12.9 to 6.1%. PMID:26521460

  13. High Resolution ECG for Evaluation of QT Interval Variability during Exposure to Acute Hypoxia

    NASA Technical Reports Server (NTRS)

    Zupet, P.; Finderle, Z.; Schlegel, Todd T.; Starc, V.

    2010-01-01

    Ventricular repolarization instability as quantified by the index of QT interval variability (QTVI) is one of the best predictors for risk of malignant ventricular arrhythmias and sudden cardiac death. Because it is difficult to appropriately monitor early signs of organ dysfunction at high altitude, we investigated whether high resolution advanced ECG (HR-ECG) analysis might be helpful as a non-invasive and easy-to-use tool for evaluating the risk of cardiac arrhythmias during exposure to acute hypoxia. 19 non-acclimatized healthy trained alpinists (age 37, 8 plus or minus 4,7 years) participated in the study. Five-minute high-resolution 12-lead electrocardiograms (ECGs) were recorded (Cardiosoft) in each subject at rest in the supine position breathing room air and then after breathing 12.5% oxygen for 30 min. For beat-to-beat RR and QT variability, the program of Starc was utilized to derive standard time domain measures such as root mean square of the successive interval difference (rMSSD) of RRV and QTV, the corrected QT interval (QTc) and the QTVI in lead II. Changes were evaluated with paired-samples t-test with p-values less than 0.05 considered statistically significant. As expected, the RR interval and its variability both decreased with increasing altitude, with p = 0.000 and p = 0.005, respectively. Significant increases were found in both the rMSSDQT and the QTVI in lead II, with p = 0.002 and p = 0.003, respectively. There was no change in QTc interval length (p = non significant). QT variability parameters may be useful for evaluating changes in ventricular repolarization caused by hypoxia. These changes might be driven by increases in sympathetic nervous system activity at ventricular level.

  14. Sildenafil improves cardiac output and exercise performance during acute hypoxia, but not normoxia.

    PubMed

    Hsu, Andrew R; Barnholt, Kimberly E; Grundmann, Nicolas K; Lin, Joseph H; McCallum, Stewart W; Friedlander, Anne L

    2006-06-01

    Sildenafil causes pulmonary vasodilation, thus potentially reducing impairments of hypoxia-induced pulmonary hypertension on exercise performance at altitude. The purpose of this study was to determine the effects of sildenafil during normoxic and hypoxic exercise. We hypothesized that 1) sildenafil would have no significant effects on normoxic exercise, and 2) sildenafil would improve cardiac output, arterial oxygen saturation (SaO2), and performance during hypoxic exercise. Ten trained men performed one practice and three experimental trials at sea level (SL) and simulated high altitude (HA) of 3,874 m. Each cycling test consisted of a set-work-rate portion (55% work capacity: 1 h SL, 30 min HA) followed immediately by a time trial (10 km SL, 6 km HA). Double-blinded capsules (placebo, 50, or 100 mg) were taken 1 h before exercise in a randomly counterbalanced order. For HA, subjects also began breathing hypoxic gas (12.8% oxygen) 1 h before exercise. At SL, sildenafil had no effects on any cardiovascular or performance measures. At HA, sildenafil increased stroke volume (measured by impedance cardiography), cardiac output, and SaO2 during set-work-rate exercise. Sildenafil lowered 6-km time-trial time by 15% (P<0.05). SaO2 was also higher during the time trial (P<0.05) in response to sildenafil, despite higher work rates. Post hoc analyses revealed two subject groups, sildenafil responders and nonresponders, who improved time-trial performance by 39% (P<0.05) and 1.0%, respectively. No dose-response effects were observed. During cycling exercise in acute hypoxia, sildenafil can greatly improve cardiovascular function, SaO2, and performance for certain individuals. PMID:16455814

  15. Repetitive acute intermittent hypoxia increases growth/neurotrophic factor expression in non-respiratory motor neurons.

    PubMed

    Satriotomo, I; Nichols, N L; Dale, E A; Emery, A T; Dahlberg, J M; Mitchell, G S

    2016-05-13

    Repetitive acute intermittent hypoxia (rAIH) increases growth/trophic factor expression in respiratory motor neurons, thereby eliciting spinal respiratory motor plasticity and/or neuroprotection. Here we demonstrate that rAIH effects are not unique to respiratory motor neurons, but are also expressed in non-respiratory, spinal alpha motor neurons and upper motor neurons of the motor cortex. In specific, we used immunohistochemistry and immunofluorescence to assess growth/trophic factor protein expression in spinal sections from rats exposed to AIH three times per week for 10weeks (3×wAIH). 3×wAIH increased brain-derived neurotrophic factor (BDNF), its high-affinity receptor, tropomyosin receptor kinase B (TrkB), and phosphorylated TrkB (pTrkB) immunoreactivity in putative alpha motor neurons of spinal cervical 7 (C7) and lumbar 3 (L3) segments, as well as in upper motor neurons of the primary motor cortex (M1). 3×wAIH also increased immunoreactivity of vascular endothelial growth factor A (VEGFA), the high-affinity VEGFA receptor (VEGFR-2) and an important VEGF gene regulator, hypoxia-inducible factor-1α (HIF-1α). Thus, rAIH effects on growth/trophic factors are characteristic of non-respiratory as well as respiratory motor neurons. rAIH may be a useful tool in the treatment of disorders causing paralysis, such as spinal injury and motor neuron disease, as a pretreatment to enhance motor neuron survival during disease, or as preconditioning for cell-transplant therapies. PMID:26944605

  16. Acute, severe bilirubin encephalopathy in a newborn.

    PubMed

    Mollen, Thomas J; Scarfone, Richard; Harris, Mary Catherine

    2004-09-01

    In recent years, changes in health care practices including the early discharge of newborns have transformed the management of neonatal jaundice into an outpatient problem. At the same time, there has been a resurgence in the incidence of kernicterus. We report the case of a term male infant who presented to our emergency department at 4 days of age with severe jaundice and who subsequently died with autopsy findings of kernicterus. We review the infant's presentation and hospital course, diagnostic and therapeutic interventions, and autopsy findings. In the current era of increased frequency of breast-feeding, shortened hospital stays, and inconsistent follow-up after hospital discharge, emergency department physicians should be alerted to the rare but increasing occurrence of severe hyperbilirubinemia and kernicterus. PMID:15599261

  17. Severe acute pancreatitis: nutritional management in the ICU.

    PubMed

    Kaushik, Neeraj; O'Keefe, Stephen J D

    2004-02-01

    Patients with acute pancreatitis have elevated nutritional needs due to increased energy expenditure and catabolism. It is a clinical challenge to provide adequate nutrition to these patients while maintaining gut function, preventing pancreatic stimulation, and minimizing the risk of septic and metabolic complications associated with nutritional support. We present the case of a patient who had severe acute pancreatitis and was initially given total parenteral nutrition. After a period of initial improvement, he developed hyperglycemia, bacteremia, and sepsis. Parenteral nutrition was discontinued and infection was treated with antibiotics. Subsequent nutritional support consisted of enteral feeding with an elemental diet infused via a nasojejunal feeding tube. His condition improved gradually and he made a full recovery. This case illustrates the difficulties encountered while managing a case of severe acute pancreatitis and provides an evidence based approach to the nutritional management of severe acute pancreatitis in the intensive care unit setting. PMID:16215093

  18. Severe Hypotension, Hypoxia, and Subcutaneous Erythema Induced by Indigo Carmine Administration during Open Prostatectomy

    PubMed Central

    Voelzke, Bryan B.

    2016-01-01

    Indigo carmine (also known as 5,5′-indigodisulfonic acid sodium salt or indigotine) is a blue dye that is administered intravenously to examine the urinary tract and usually is biologically safe and inert. Indigo carmine rarely may cause adverse reactions. We treated a 66-year-old man who had general anesthesia and radical retropubic prostatectomy for prostate cancer. He had a previous history of allergy to bee sting with nausea, vomiting, and dizziness. Within 1 minute after injection of indigo carmine for evaluation of the ureters, the patient developed hypotension to 40 mmHg, severe hypoxia (the value of SpO2 (peripheral capillary oxygen saturation) was 75% on 40% inspired oxygen concentration), poor air movement and bilateral diffuse wheezing on auscultation, and marked subcutaneous erythema at the upper extremities. After treatment with 100% oxygen, epinephrine (total, 1.5 mg), hydrocortisone (100 mg), diphenhydramine (50 mg), albuterol nebulizer (0.083%), and continuous infusion of epinephrine (0.15 μg/kg/min), the vital signs became stable, and he recovered completely. In summary, indigo carmine rarely may cause life-threatening anaphylactic or anaphylactoid reaction that may necessitate rapid treatment to stabilize cardiovascular, hemodynamic, and pulmonary function. PMID:27610263

  19. Severe Hypotension, Hypoxia, and Subcutaneous Erythema Induced by Indigo Carmine Administration during Open Prostatectomy.

    PubMed

    Nandate, Koichiro; Voelzke, Bryan B

    2016-01-01

    Indigo carmine (also known as 5,5'-indigodisulfonic acid sodium salt or indigotine) is a blue dye that is administered intravenously to examine the urinary tract and usually is biologically safe and inert. Indigo carmine rarely may cause adverse reactions. We treated a 66-year-old man who had general anesthesia and radical retropubic prostatectomy for prostate cancer. He had a previous history of allergy to bee sting with nausea, vomiting, and dizziness. Within 1 minute after injection of indigo carmine for evaluation of the ureters, the patient developed hypotension to 40 mmHg, severe hypoxia (the value of SpO2 (peripheral capillary oxygen saturation) was 75% on 40% inspired oxygen concentration), poor air movement and bilateral diffuse wheezing on auscultation, and marked subcutaneous erythema at the upper extremities. After treatment with 100% oxygen, epinephrine (total, 1.5 mg), hydrocortisone (100 mg), diphenhydramine (50 mg), albuterol nebulizer (0.083%), and continuous infusion of epinephrine (0.15 μg/kg/min), the vital signs became stable, and he recovered completely. In summary, indigo carmine rarely may cause life-threatening anaphylactic or anaphylactoid reaction that may necessitate rapid treatment to stabilize cardiovascular, hemodynamic, and pulmonary function. PMID:27610263

  20. Role of Recurrent Hypoxia-Ischemia in Preterm White Matter Injury Severity

    PubMed Central

    Hagen, Matthew W.; Riddle, Art; McClendon, Evelyn; Gong, Xi; Shaver, Daniel; Srivastava, Taasin; Dean, Justin M.; Bai, Ji-Zhong; Fowke, Tania M.; Gunn, Alistair J.; Jones, Daniel F.; Sherman, Larry S.; Grafe, Marjorie R.; Hohimer, A. Roger; Back, Stephen A.

    2014-01-01

    Objective Although the spectrum of white matter injury (WMI) in preterm infants is shifting from cystic necrotic lesions to milder forms, the factors that contribute to this changing spectrum are unclear. We hypothesized that recurrent hypoxia-ischemia (rHI) will exacerbate the spectrum of WMI defined by markers of inflammation and molecules related to the extracellular matrix (hyaluronan (HA) and the PH20 hyaluronidase) that regulate maturation of the oligodendrocyte (OL) lineage after WMI. Methods We employed a preterm fetal sheep model of in utero moderate hypoxemia and global severe but not complete cerebral ischemia that reproduces the spectrum of human WMI. The response to rHI was compared against corresponding early or later single episodes of HI. An ordinal rating scale of WMI was compared against an unbiased quantitative image analysis protocol that provided continuous histo-pathological outcome measures for astrogliosis and microglial activation. Late oligodendrocyte progenitors (preOLs) were quantified by stereology. Analysis of hyaluronan and the hyaluronidase PH20 defined the progressive response of the extracellular matrix to WMI. Results rHI resulted in a more severe spectrum of WMI with a greater burden of necrosis, but an expanded population of preOLs that displayed reduced susceptibility to cell death. WMI from single episodes of HI or rHI was accompanied by elevated HA levels and increased labeling for PH20. Expression of PH20 in fetal ovine WMI was confirmed by RT-PCR and RNA-sequencing. Conclusions rHI is associated with an increased risk for more severe WMI with necrosis, but reduced risk for preOL degeneration compared to single episodes of HI. Expansion of the preOL pool may be linked to elevated hyaluronan and PH20. PMID:25390897

  1. Ethyl 3,4-dihydroxybenzoate (EDHB): a prolyl hydroxylase inhibitor attenuates acute hypobaric hypoxia mediated vascular leakage in brain.

    PubMed

    Singh, Deependra Pratap; Nimker, Charu; Paliwal, Piyush; Bansal, Anju

    2016-07-01

    Sudden exposure to altitude hypoxia is responsible for acute mountain sickness (AMS) in un-acclimatized persons. If not treated in time, AMS can worsen and leads to high altitude cerebral edema, which can be fatal. Present study explores the efficacy of ethyl 3,4-dihydroxybenzoate (EDHB), a prolyl hydroxylase enzyme inhibitor, in modulating adaptive responses to hypobaric hypoxia (HH) in rat brain. Male Sprague-Dawley rats treated with EDHB (75 mg/kg for 3 days), were subjected to acute HH exposure at 9144 m (30,000 ft) for 5 h. Animals were assessed for transvascular leakage and edema formation in brain and role of key inflammatory markers along with hypoxia responsive genes. HH stress increased transvascular permeability and edema formation in conjunction with upregulation of nuclear factor-κB (NF-κB) and its regulated proteins. There was surge in pro-inflammatory cytokines tumor necrosis factor-α, interleukin-6, interferon-γ, monocyte chemoattractant protein-1 and decrement in anti-inflammatory cytokine interleukin-10. Further, upregulation of vascular endothelial growth factor (VEGF), a vascular permeability marker and down-regulation of antioxidant and anti-inflammatory proteins hemoxygenase (HO-1) and metallothionein (MT-1) was also observed under hypoxia. EDHB supplementation effectively scaled down HH induced cerebral edema with concomitant downregulation of brain NF-κB expression. There was significant curtailment of pro-inflammatory cytokines and cell adhesion molecules. There was significant downregulation of permeability factor VEGF by EDHB with concomitant increment in hypoxia inducible factor (HIF1α) and anti-inflammatory proteins HO-1 and MT-1 compared to HH control thus accentuating the potential of EDHB as effective hypoxic preconditioning agent in ameliorating HH mediated injury in brain. PMID:26649730

  2. Liver transplantation for acute liver failure accompanied by severe acute pancreatitis.

    PubMed

    Kirino, Izumi; Fujimoto, Yasuhiro; Hata, Koichiro; Uemoto, Shinji

    2016-01-01

    The role of liver transplantation (LT) in acute liver failure (ALF) complicated by severe acute pancreatitis is still unclear. We here report a case of deceased-donor LT for idiopathic ALF accompanied by severe acute pancreatitis. A 58-year-old man with no history of liver disease presented with idiopathic ALF and acute pancreatitis. After careful consideration, he received a liver from a deceased donor. Following surgery, the patient's liver function rapidly reverted to normal level and the acute pancreatitis simultaneously subsided. The patient later developed a pancreatic pseudocyst, which was treated successfully with combination interventional radiology. LT can be considered for ALF associated with severe acute pancreatitis if there is no clinical evidence of an absolute contraindication for organ transplantation, such as systemic or local infection. Moreover, we recommend a close follow-up by ultrasonography to allow early detection and treatment of pancreatic pseudocysts following surgery. PMID:27600056

  3. Emergency presentation and management of acute severe asthma in children

    PubMed Central

    Øymar, Knut; Halvorsen, Thomas

    2009-01-01

    Acute severe asthma is one of the most common medical emergency situations in childhood, and physicians caring for acutely ill children are regularly faced with this condition. In this article we present a summary of the pathophysiology as well as guidelines for the treatment of acute severe asthma in children. The cornerstones of the management of acute asthma in children are rapid administration of oxygen, inhalations with bronchodilators and systemic corticosteroids. Inhaled bronchodilators may include selective b2-agonists, adrenaline and anticholinergics. Additional treatment in selected cases may involve intravenous administration of theophylline, b2-agonists and magnesium sulphate. Both non-invasive and invasive ventilation may be options when medical treatment fails to prevent respiratory failure. It is important that relevant treatment algorithms exist, applicable to all levels of the treatment chain and reflecting local considerations and circumstances. PMID:19732437

  4. Single-subject statistical mapping of acute brain hypoxia in the rat following middle cerebral artery occlusion: a microPET study.

    PubMed

    Takasawa, Masashi; Beech, John S; Fryer, Tim D; Jones, P Simon; Ahmed, Tahir; Smith, Rob; Aigbirhio, Franklin I; Baron, Jean-Claude

    2011-06-01

    No study so far has attempted to map the 3D topography of brain hypoxia in the individual rat in vivo following middle cerebral artery occlusion (MCAo). In a previous microPET study, we reported that (18)F-fluoromisonidazole ((18)F-MISO) trapping in the brain after MCAo was specific for the hypoxic viable tissue. Here, we used (18)F-MISO microPET to map the 3D topography of brain hypoxia in the acute stage of permanent distal MCAo in individual spontaneously hypertensive rats. Normal rats were also studied. (18)F-MISO was intravenously injected approximately 1 h after clip placement and PET data were acquired for 2 hours. Animals were sacrificed and the brains harvested 48 h later for infarct mapping using standard histopathology. As expected, continuous (18)F-MISO trapping was found over the affected relative to unaffected and control MCA cortex. Using single-subject voxel-based statistical mapping, tracer accumulation 90-120 min after injection was consistently significantly higher in the anterior MCA cortex (proximal relative to clip site) and gradually decreased towards posterior areas, a pattern consistent with the classic penumbra concept. The data also suggested that (i) a portion of the significant (18)F-MISO trapping area may sit outside the contours of the final infarct despite the permanent MCAo, suggesting that (18)F-MISO may be a marker not only of severe (penumbral) but also of milder (oligemic) hypoxia, and (ii) small portions of the final infarct may not exhibit early tracer trapping, suggesting that by the time the tracer was administered this tissue had already progressed to irreversible damage. This study shows the feasibility of single-subject mapping of brain hypoxia following MCAo in the rat, which has potential applications in pathophysiological investigations. PMID:21335004

  5. Severe hypoxia exerts parallel and cell-specific regulation of gene expression and alternative splicing in human mesenchymal stem cells

    PubMed Central

    2014-01-01

    Background The endosteum of the bone marrow provides a specialized hypoxic niche that may serve to preserve the integrity, pluripotency, longevity and stemness of resident mesenchymal stem cells (MSCs). To explore the molecular genetic consequences of such a niche we subjected human (h) MSCs to a pO2 of 4 mmHg and analyzed global gene expression and alternative splicing (AS) by genome-exon microarray and RT-qPCR, and phenotype by western blot and immunostaining. Results Out of 446 genes differentially regulated by >2.5-fold, down-regulated genes outnumbered up-regulated genes by 243:203. Exon analyses revealed 60 hypoxia-regulated AS events with splice indices (SI) >1.0 from 53 genes and a correlation between high SI and degree of transcript regulation. Parallel analyses of a publicly available AS study on human umbilical vein endothelial cells (HUVECs) showed that there was a strong cell-specific component with only 11 genes commonly regulated in hMSCs and HUVECs and 17 common differentially spliced genes. Only 3 genes were differentially responsive to hypoxia at the gene (>2.0) and AS levels in both cell types. Functional assignments revealed unique profiles of gene expression with complex regulation of differentiation, extracellular matrix, intermediate filament and metabolic marker genes. Antioxidant genes, striated muscle genes and insulin/IGF-1 signaling intermediates were down-regulated. There was a coordinate induction of 9 out of 12 acidic keratins that along with other epithelial and cell adhesion markers implies a partial mesenchymal to epithelial transition. Conclusions We conclude that severe hypoxia confers a quiescent phenotype in hMSCs that is reflected by both the transcriptome profile and gene-specific changes of splicosome actions. The results reveal that severe hypoxia imposes markedly different patterns of gene regulation of MSCs compared with more moderate hypoxia. This is the first study to report hypoxia-regulation of AS in stem

  6. CO2-O2 Interactions in Extension of Tolerance to Acute Hypoxia

    NASA Technical Reports Server (NTRS)

    Lambertsen, C. J.; Gelfand, R.

    1996-01-01

    Advantageous and/or detrimental influences associated with purposeful deviations from atmospheric levels of O2 and CO2 are studied. Specific goals have been directed to simulating situations of emergency or accidental exposure to hypoxic (10% O2) environments. They included establishing dynamic effects of hypoxia with and without CO2 (rate of acute adaptation), and stable-state (equilibrium) effects on blood and brain oxygenation. They also included effects on the physiological parameters of respiration and blood gas composition which underlie brain oxygenation. For 10% O2, a complete experiment consisted of three identical rest-exercise phases of 32 minutes duration. Following a five minute air control period, each inspired gas was administered over the next 27 minutes. The test gases were room air control, 10% +/- 0.1% O2 with 4% +/- 0.1% CO2, and 10% +/- 0.1% O2. A minimum of 45 minutes separated each phase. Relative to inspiration of 10% O2, brain oxygenation is enhanced by addition of 4% CO2. This is accomplished by increasing the rate at which O2 in arterial blood is supplied to the brain circulation (well above even the normoxic level), and on relative improvement in the arterial pressure of O2.

  7. NADPH oxidase activity is necessary for acute intermittent hypoxia-induced phrenic long-term facilitation

    PubMed Central

    MacFarlane, P M; Satriotomo, I; Windelborn, J A; Mitchell, G S

    2009-01-01

    Phrenic long-term facilitation (pLTF) following acute intermittent hypoxia (AIH) is a form of spinal, serotonin-dependent synaptic plasticity that requires reactive oxygen species (ROS) formation. We tested the hypothesis that spinal NADPH oxidase activity is a necessary source of ROS for pLTF. Sixty minutes post-AIH (three 5-min episodes of 11% O2, 5 min intervals), integrated phrenic and hypoglossal (XII) nerve burst amplitudes were increased from baseline, indicative of phrenic and XII LTF. Intrathecal injections (∼C4) of apocynin or diphenyleneiodonium chloride (DPI), two structurally and functionally distinct inhibitors of the NADPH oxidase complex, attenuated phrenic, but not XII, LTF. Immunoblots from soluble (cytosolic) and particulate (membrane) fractions of ventral C4 spinal segments revealed predominantly membrane localization of the NADPH oxidase catalytic subunit, gp91phox, whereas membrane and cytosolic expression were both observed for the regulatory subunits, p47phox and RAC1. Immunohistochemical analysis of fixed tissues revealed these same subunits in presumptive phrenic motoneurons of the C4 ventral horn, but not in neighbouring astrocytes or microglia. Collectively, these data demonstrate that NADPH oxidase subunits localized within presumptive phrenic motoneurons are a major source of ROS necessary for AIH-induced pLTF. Thus, NADPH oxidase activity is a key regulator of spinal synaptic plasticity, and may be a useful pharmaceutical target in developing therapeutic strategies for respiratory insufficiency in patients with, for example, cervical spinal injury. PMID:19237427

  8. Effects of acute intermittent hypoxia on energy balance and hypothalamic feeding pathways.

    PubMed

    Moreau, J M; Ciriello, J

    2013-12-01

    This study was done to investigate the effects of acute intermittent hypoxia (IH) on metabolic factors associated with energy balance and body weight, and on hypothalamic satiety-inducing pathways. Adult male Sprague-Dawley rats were exposed to either 8h IH or normoxic control conditions. Food intake, locomotion and body weights were examined after IH. Additionally, plasma levels of leptin, adiponectin corticosterone, insulin and blood glucose were measured following exposure to IH. Furthermore, adipose tissue was removed and analyzed for leptin and adiponectin content. Finally, the hypothalamic arcuate nucleus (ARC) was assessed for alterations in protein signaling associated with satiety. IH reduced body weight, food intake and active cycle locomotion without altering adipose tissue mass. Leptin protein content was reduced while adiponectin content was elevated in adipose tissue after IH. Plasma concentration of leptin was significantly increased while adiponectin decreased after IH. No changes were found in plasma corticosterone, insulin and blood glucose. In ARC, phosphorylation of signal transducer and activator of transcription-3 and pro-opiomelanocortin (POMC) expression were elevated. In addition, POMC-expressing neurons were activated as determined by immediate early gene FRA-1/2 expression. Finally, ERK1/2 and its phosphorylation were reduced in response to IH. These data suggest that IH induces significant alterations to body energy balance through changes in the secretion of leptin which exert effects on satiety-inducing pathways within the hypothalamus. PMID:24042039

  9. Modulated expression and enzymatic activities of Darkbarbel catfish, Pelteobagrus vachelli for oxidative stress induced by acute hypoxia and reoxygenation.

    PubMed

    Zhang, Guosong; Mao, Jianqiang; Liang, Fenfei; Chen, Jiawei; Zhao, Cheng; Yin, Shaowu; Wang, Li; Tang, Zhonglin; Chen, Shuqiao

    2016-05-01

    Large changes in oxygen availability in aquatic environments, ranging from anoxia through to hyperoxia, can lead to corresponding wide variation in the production of reactive oxygen species (ROS) by fish with aquatic respiration. In order to evaluate the effects of hypoxia and reoxygenation on oxidative stress in fish, the mRNA and protein expression of SODs (Cu/Zn-SOD and Mn-SOD) as well as indices (CP, LPO and MDA) and enzymatic activities (SOD, CAT, GPx, GR and GST) were analyzed in liver and brain tissues of Pelteobagrus vachelli. Predominant expression of PvSOD2 was detected in heart, brain, and liver. In contrast, PvSOD1 was highly expressed in liver. Based on the expression patterns of above parameters, we inferred that brain tissue of P. vachelli under 0.7 mg/L degree of acute hypoxia condition could experience hypometabolic states or no suffering stress, but brain tissue has effective mechanisms to minimize or prevent oxidative stress during the transition from hypoxia to reoxygenation. Our results also demonstrated an increased expression of SODs and enzymatic activities for oxidative stress in liver under hypoxic conditions, which supports the hypothesis that anticipatory preparation takes place in order to deal with the encountered oxidative stress during the recovery from hypoxia as proposed by M. Hermes-Lima. Therefore, this study will provide a clue to better understand the action mode of antioxidant genes and enzymes under oxidative stress in fish. PMID:26945243

  10. Acute renal failure and severe thrombocytopenia associated with metamizole.

    PubMed

    Redondo-Pachon, Maria Dolores; Enriquez, Ricardo; Sirvent, Ana Esther; Millan, Isabel; Romero, Alberto; Amorós, Francisco

    2014-01-01

    Metamizole or dipyrone is a pyrazolone derivative that belongs to the non-steroidal anti-inflammatory drugs. Its main side-effect is hematological toxicity. Thrombocytopenia due to metamizole is rare and is usually associated with the involvement of the two other blood series. Drug-induced thrombocytopenia is more frequently related to immune mechanisms, and the diagnosis is still largely made by exclusion of other causes and by correlation of timing of thrombocytopenia with the administration of drug. Metamizole may cause acute renal failure due to hemodynamic renal failure/acute tubular necrosis and/or acute tubulointerstitial nephritis. We report a case of acute renal failure and severe thrombocytopenia after metamizole. As far as we know, this combination of adverse effects from this drug has not been reported previously. PMID:24434395

  11. Upregulation of Steroidogenic Acute Regulatory Protein by Hypoxia Stimulates Aldosterone Synthesis in Pulmonary Artery Endothelial Cells to Promote Pulmonary Vascular Fibrosis

    PubMed Central

    Maron, Bradley A.; Oldham, William M.; Chan, Stephen Y.; Vargas, Sara O.; Arons, Elena; Zhang, Ying-Yi; Loscalzo, Joseph; Leopold, Jane A.

    2014-01-01

    Background The molecular mechanism(s) regulating hypoxia-induced vascular fibrosis are unresolved. Hyperaldosteronism correlates positively with vascular remodeling in pulmonary arterial hypertension (PAH), suggesting that aldosterone may contribute to the pulmonary vasculopathy of hypoxia. The hypoxia-sensitive transcription factors c-Fos/c-Jun regulate steroidogenic acute regulatory protein (StAR), which facilitates the rate-limiting step of aldosterone steroidogenesis. We hypothesized that c-Fos/c-Jun upregulation by hypoxia activates StAR-dependent aldosterone synthesis in human pulmonary artery endothelial cells (HPAECs) to promote vascular fibrosis in PAH. Methods and Results Patients with PAH, rats with Sugen/hypoxia-PAH, and mice exposed to chronic hypoxia expressed increased StAR in remodeled pulmonary arterioles, providing a basis for investigating hypoxia-StAR signaling in HPAECs. Hypoxia (2.0% FiO2) increased aldosterone levels selectively in HPAECs, which was confirmed by liquid chromatography-mass spectrometry. Increased aldosterone by hypoxia resulted from enhanced c-Fos/c-Jun binding to the proximal activator protein (AP-1) site of the StAR promoter in HPAECs, which increased StAR expression and activity. In HPAECs transfected with StAR-siRNA or treated with the AP-1 inhibitor, SR-11302, hypoxia failed to increase aldosterone, confirming that aldosterone biosynthesis required StAR activation by c-Fos/c-Jun. The functional consequences of aldosterone were confirmed by pharmacological inhibition of the mineralocorticoid receptor with spironolactone or eplerenone, which attenuated hypoxia-induced upregulation of the fibrogenic protein connective tissue growth factor and collagen III in vitro, and decreased pulmonary vascular fibrosis to improve pulmonary hypertension in Conclusions Our findings identify autonomous aldosterone synthesis in HPAECs due to hypoxia-mediated upregulation of StAR as a novel molecular mechanism that promotes pulmonary vascular

  12. Psychosocial Care and its Association with Severe Acute Malnutrition.

    PubMed

    Singh, Anurag; Agarwal, Sheesham

    2016-05-01

    This cross-sectional study compared 120 children having severe acute malnutrition with 120 healthy children for exposure to 40 behaviors, by measuring psychosocial care based on Home Observation for Measurement of the Environment (HOME) inventory. The mean (SD) psychosocial care score of cases and controls significantly differed [18.2 (2.2) vs 23.5 (2.1); P<0.001]. A score of less than 14 was significantly associated with severe acute malnutrition (OR 23.2; 95% CI 8.2, 50). PMID:27254059

  13. Effect of sinusoidal modulated currents and acute hypoxia on corticosterone content and activity of certain dehydrogenases in tissues of different rat organs during hypokinesia

    NASA Technical Reports Server (NTRS)

    Melik-Aslanova, L. L.; Frenkel, I. D.

    1980-01-01

    The state of hypokinesia in rats was reproduced by keeping them for 30 days in special box cages that restricted their mobility in all directions. Results show the resistance to acute hypoxic hypoxia is increased. This is linked to the considerable rise in the reduced level of corticosterone in different organs and the succinate dehydrogenase activity in the liver and brain. The letter indicated the primary oxidation of succinate, which has great importance in the adaptation of the oxidative metabolism to acute oxygen insufficiency. The use of sinusoidal modulated currents in the period of hypokinesia promotes normalization of the indices for resistance of the rats to acute hypoxia.

  14. Cross Acclimation between Heat and Hypoxia: Heat Acclimation Improves Cellular Tolerance and Exercise Performance in Acute Normobaric Hypoxia

    PubMed Central

    Lee, Ben J.; Miller, Amanda; James, Rob S.; Thake, Charles D.

    2016-01-01

    Background: The potential for cross acclimation between environmental stressors is not well understood. Thus, the aim of this investigation was to determine the effect of fixed-workload heat or hypoxic acclimation on cellular, physiological, and performance responses during post acclimation hypoxic exercise in humans. Method: Twenty-one males (age 22 ± 5 years; stature 1.76 ± 0.07 m; mass 71.8 ± 7.9 kg; V˙O2 peak 51 ± 7 mL.kg−1.min−1) completed a cycling hypoxic stress test (HST) and self-paced 16.1 km time trial (TT) before (HST1, TT1), and after (HST2, TT2) a series of 10 daily 60 min training sessions (50% N V˙O2 peak) in control (CON, n = 7; 18°C, 35% RH), hypoxic (HYP, n = 7; fraction of inspired oxygen = 0.14, 18°C, 35% RH), or hot (HOT, n = 7; 40°C, 25% RH) conditions. Results: TT performance in hypoxia was improved following both acclimation treatments, HYP (−3:16 ± 3:10 min:s; p = 0.0006) and HOT (−2:02 ± 1:02 min:s; p = 0.005), but unchanged after CON (+0:31 ± 1:42 min:s). Resting monocyte heat shock protein 72 (mHSP72) increased prior to HST2 in HOT (62 ± 46%) and HYP (58 ± 52%), but was unchanged after CON (9 ± 46%), leading to an attenuated mHSP72 response to hypoxic exercise in HOT and HYP HST2 compared to HST1 (p < 0.01). Changes in extracellular hypoxia-inducible factor 1-α followed a similar pattern to those of mHSP72. Physiological strain index (PSI) was attenuated in HOT (HST1 = 4.12 ± 0.58, HST2 = 3.60 ± 0.42; p = 0.007) as a result of a reduced HR (HST1 = 140 ± 14 b.min−1; HST2 131 ± 9 b.min−1 p = 0.0006) and Trectal (HST1 = 37.55 ± 0.18°C; HST2 37.45 ± 0.14°C; p = 0.018) during exercise. Whereas PSI did not change in HYP (HST1 = 4.82 ± 0.64, HST2 4.83 ± 0.63). Conclusion: Heat acclimation improved cellular and systemic physiological tolerance to steady state exercise in moderate hypoxia. Additionally we show, for the first time, that heat acclimation improved cycling time trial performance to a magnitude

  15. Serotonin in the dorsal periaqueductal gray inhibits panic-like defensive behaviors in rats exposed to acute hypoxia.

    PubMed

    Spiacci, A; Sergio, T de Oliveira; da Silva, G S F; Glass, M L; Schenberg, L C; Garcia-Cairasco, N; Zangrossi, H

    2015-10-29

    It has been proposed that spontaneous panic attacks are the outcome of the misfiring of an evolved suffocation alarm system. Evidence gathered in the last years is suggestive that the dorsal periaqueductal gray (dPAG) in the midbrain harbors a hypoxia-sensitive suffocation alarm system. We here investigated whether facilitation of 5-HT-mediated neurotransmission within the dPAG changes panic-like defensive reactions expressed by male Wistar rats submitted to a hypoxia challenge (7% O2), as observed in other animal models of panic. Intra-dPAG injection of 5-HT (20 nmol), (±)-8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide (8-OH-DPAT) (8 nmol), a 5-HT1A receptor agonist, or (±)-2,5-dimethoxy-4-iodo amphetamine hydrochloride (DOI) (16 nmol), a preferential 5-HT2A agonist, reduced the number of upward jumps directed to the border of the experimental chamber during hypoxia, interpreted as escape attempts, without affecting the rats' locomotion. These effects were similar to those caused by chronic, but not acute, intraperitoneal administration of the antidepressant fluoxetine (5-15 mg/kg), or acute systemic administration of the benzodiazepine receptor agonist alprazolam (1-4 mg/kg), both drugs clinically used in the treatment of panic disorder. Our findings strengthen the view that the dPAG is a key encephalic area involved in the defensive behaviors triggered by activation of the suffocation alarm system. They also support the use of hypoxia-evoked escape as a model of respiratory-type panic attacks. PMID:26319117

  16. S1P prophylaxis mitigates acute hypobaric hypoxia-induced molecular, biochemical, and metabolic disturbances: A preclinical report.

    PubMed

    Chawla, Sonam; Rahar, Babita; Saxena, Shweta

    2016-05-01

    Sphingosine-1-phosphate (S1P) is emerging to have hypoxic preconditioning potential in various preclinical studies. The study aims to evaluate the preclinical preconditioning efficacy of exogenously administered S1P against acute hypobaric hypoxia (HH)-induced pathological disturbances. Male Sprague Dawley rats (200 ± 20 g) were preconditioned with 1, 10, and 100 μg/kg body weight (b.w.) S1P (i.v.) for three consecutive days. On the third day, S1P preconditioned animals, along with hypoxia control animals, were exposed to HH equivalent to 7,620 m (280 mm Hg) for 6 h. Postexposure status of cardiac energy production, circulatory vasoactive mediators, pulmonary and cerebral oxidative damage, and inflammation were assessed. HH exposure led to cardiac energy deficit indicated by low ATP levels and pronounced AMPK activation levels, raised circulatory levels of brain natriuretic peptide and endothelin-1 with respect to total nitrate (NOx), redox imbalance, inflammation, and alterations in NOx levels in the pulmonary and cerebral tissues. These pathological precursors have been routinely reported to be coincident with high-altitude diseases. Preconditioning with S1P, especially 1 µg/kg b.w. dose, was seen to reverse the manifestation of these pathological disturbances. The protective efficacy could be attributed, at least in part, to enhanced activity of cardioprotective protein kinase C and activation of small GTPase Rac1, which led to further induction of hypoxia-adaptive molecular mediators: hypoxia-inducible factor (HIF)-1α and Hsp70. This is a first such report, to the best of our knowledge, elucidating the mechanism of exogenous S1P-mediated HIF-1α/Hsp70 induction. Conclusively, systemic preconditioning with 1 μg/kg b.w. S1P in rats protects against acute HH-induced pathological disturbances. © 2016 IUBMB Life 68(5):365-375, 2016. PMID:26959531

  17. Effects of hypoxia-induced neonatal seizures on acute hippocampal injury and later-life seizure susceptibility and anxiety-related behavior in mice.

    PubMed

    Rodriguez-Alvarez, Natalia; Jimenez-Mateos, Eva M; Dunleavy, Mark; Waddington, John L; Boylan, Geraldine B; Henshall, David C

    2015-11-01

    Seizures are common during the neonatal period, often due to hypoxic-ischemic encephalopathy and may contribute to acute brain injury and the subsequent development of cognitive deficits and childhood epilepsy. Here we explored short- and long-term consequences of neonatal hypoxia-induced seizures in 7 day old C57BL/6J mice. Seizure activity, molecular markers of hypoxia and histological injury were investigated acutely after hypoxia and response to chemoconvulsants and animal behaviour was explored at adulthood. Hypoxia was induced by exposing pups to 5% oxygen for 15 min (global hypoxia). Electrographically defined seizures with behavioral correlates occurred in 95% of these animals and seizures persisted for many minutes after restitution of normoxia. There was minimal morbidity or mortality. Pre- or post-hypoxia injection of phenobarbital (50mg/kg) had limited efficacy at suppressing seizures. The hippocampus from neonatal hypoxia-seizure mice displayed increased expression of vascular endothelial growth factor and the immediate early gene c-fos, minimal histological evidence of cell injury and activation of caspase-3 in scattered neurons. Behavioral analysis of mice five weeks after hypoxia-induced seizures detected novel anxiety-related and other behaviors, while performance in a spatial memory test was similar to controls. Seizure threshold tests with kainic acid at six weeks revealed that mice previously subject to neonatal hypoxia-induced seizures developed earlier, more frequent and longer-duration seizures. This study defines a set of electro-clinical, molecular, pharmacological and behavioral consequences of hypoxia-induced seizures that indicate short- and long-term deleterious outcomes and may be a useful model to investigate the pathophysiology and treatment of neonatal seizures in humans. PMID:26341542

  18. Outbreak of severe acute respiratory syndrome--worldwide, 2003.

    PubMed

    2003-03-21

    Since late February 2003, CDC has been supporting the World Health Organization (WHO) in the investigation of a multicountry outbreak of atypical pneumonia of unknown etiology. The illness is being referred to as severe acute respiratory syndrome (SARS). This report describes the scope of the outbreak, preliminary case definition, and interim infection control guidance for the United States. PMID:12665115

  19. Severe Acute Respiratory Syndrome (SARS) Prevention in Taiwan

    ERIC Educational Resources Information Center

    Liu, Hsueh-Erh

    2004-01-01

    Severe Acute Respiratory Syndrome (SARS) is a newly identified respiratory disease that threatened Taiwan between April 14 and July 5, 2003. Chang Gung University experienced various SARS-related episodes, such as the postponement of classes for 7 days, the reporting of probable SARS cases, and the isolation of students under Level A and B…

  20. Is ketamine a lifesaving agent in childhood acute severe asthma?

    PubMed Central

    Hendaus, Mohamed A; Jomha, Fatima A; Alhammadi, Ahmed H

    2016-01-01

    Children with acute severe asthma exacerbation are at risk of developing respiratory failure. Moreover, conventional aggressive management might be futile in acute severe asthma requiring intubation and invasive ventilation. The aim of this review is to detail evidence on the use of ketamine in childhood asthma exacerbations. A search of the MEDLINE, EMBASE, and Cochrane databases was performed, using different combinations of the following terms: ketamine, asthma, use, exacerbation, and childhood. In addition, we searched the references of the identified articles for additional articles. We then reviewed titles and included studies that were relevant to the topic of interest. Finally, the search was limited to studies published in English and Spanish from 1918 to June 2015. Due to the scarcity in the literature, we included all published articles. The literature reports conflicting results of ketamine use for acute severe asthma in children. Taking into consideration the relatively good safety profile of the drug, ketamine might be a reasonable option in the management of acute severe asthma in children who fail to respond to standard therapy. Furthermore, pediatricians and pediatric emergency clinicians administering ketamine should be knowledgeable about the unique actions of this drug and its potential side effects. PMID:26955277

  1. Long-term facilitation of expiratory and sympathetic activities following acute intermittent hypoxia in rats

    PubMed Central

    Lemes, Eduardo V.; Aiko, Simone; Orbem, Caroline B.; Formentin, Cleiton; Bassi, Mirian; Colombari, Eduardo; Zoccal, Daniel B.

    2015-01-01

    Aim Acute intermittent hypoxia (AIH) promotes persistent increases in ventilation and sympathetic activity, referred as long-term facilitation (LTF). Augmented inspiratory activity is suggested as a major component of respiratory LTF. In the present study, we hypothesized that AIH also elicits a sustained increase in expiratory motor activity. We also investigated whether the expiratory LTF contributes to the development of sympathetic LTF after AIH. Methods Rats were exposed to AIH (10 × 6–7 % O2 for 45 s, every 5 min) and the cardiorespiratory parameters were evaluated during 60 min using in vivo and in situ approaches. Results In unanesthetized conditions (n=9), AIH elicited a modest but sustained increase in baseline mean arterial pressure (MAP, 104±2 vs 111±3 mmHg, P<0.05) associated with enhanced sympathetic and respiratory-related variabilities. In the in situ preparations (n=9), AIH evoked LTF in phrenic (33±12%), thoracic sympathetic (75±25%) and abdominal nerve activities (69±14%). The sympathetic overactivity after AIH was phase-locked with the emergence of bursts in abdominal activity during the late-expiratory phase. In anesthetized vagus-intact animals, AIH increased baseline MAP (113±3 vs 122±2 mmHg, P<0.05) and abdominal muscle activity (535±94%), which were eliminated after pharmacological inhibition of the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG). Conclusion These findings indicate that increased expiratory activity is also an important component of AIH-elicited respiratory LTF. Moreover, the development of sympathetic LTF after AIH is linked to the emergence of active expiratory pattern and depends on the integrity of the neurones of the RTN/pFRG. PMID:26910756

  2. Protein tyrosine kinase regulates α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking induced by acute hypoxia in cultured brainstem neurons.

    PubMed

    Wang, H; Yu, L C; Li, Y C

    2016-01-01

    This study was performed to investigate the modulation effect of protein tyrosine kinase on postsynaptic a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking induced by acute hypoxia in cultured brainstem neurons. The cultured neurons were exposed to 1% O2 and the expression of AMPA receptor subunit GluR2 on the cell surface was significantly increased, while total GluR2 was not markedly changed. Furthermore, the hypoxia-induced increase in GluR2 expression on the cell surface was partially blocked by the protein tyrosine kinase membrane-permeable inhibitor genistein. In contrast, both the protein tyrosine kinase agonist nerve growth factor and protein tyrosine phosphatase inhibitor vanadate promoted the hypoxia-induced increase of GluR2 expression on cell surface. Moreover, GluR2 could be phosphorylated by tyrosine under normoxia and hypoxia conditions in vitro on brainstem neurons, and tyrosine phosphorylation of GluR2 was significantly stronger under hypoxia conditions. Our results indicate that acute hypoxia induces the AMPA receptor subunit GluR2 to rapidly migrate to the cell membrane to modify the strength of the synapse. This study indicates that tyrosine phosphorylation of the receptor is an important pathway regulating the rapid migration of GluR2 in the postsynaptic domain induced by hypoxia. PMID:27525851

  3. Hypoxia. 4. Hypoxia and ion channel function

    PubMed Central

    Polak, Jan

    2011-01-01

    The ability to sense and respond to oxygen deprivation is required for survival; thus, understanding the mechanisms by which changes in oxygen are linked to cell viability and function is of great importance. Ion channels play a critical role in regulating cell function in a wide variety of biological processes, including neuronal transmission, control of ventilation, cardiac contractility, and control of vasomotor tone. Since the 1988 discovery of oxygen-sensitive potassium channels in chemoreceptors, the effect of hypoxia on an assortment of ion channels has been studied in an array of cell types. In this review, we describe the effects of both acute and sustained hypoxia (continuous and intermittent) on mammalian ion channels in several tissues, the mode of action, and their contribution to diverse cellular processes. PMID:21178108

  4. Meteorological parameters and severity of acute pulmonary embolism episodes.

    PubMed

    Staśkiewicz, Grzegorz; Czekajska-Chehab, Elżbieta; Przegaliński, Jerzy; Maciejewski, Marcin; Pachowicz, Marcin; Drop, Andrzej

    2011-01-01

    Frequency of acute pulmonary embolism episodes has been previously shown to correlate significantly with meteorological factors in the period preceding their occurrence. The purpose of the study was to analyze the relation of meteorological factors and the severity of acute pulmonary embolism, expressed by the CT-based pulmonary obstruction score. A retrospective analysis of medical data of 182 consecutive patients with acute pulmonary embolism diagnosed with CT pulmonary angiography was performed. Severity of pulmonary obstruction was assessed by analysis of CT pulmonary angiography examinations, and defined with pulmonary obstruction score by Qanadli et al. The study group was divided into low (L group, 95 patients) and high PE severity (H group, 87 patients), with a cutoff value of 50% of maximum pulmonary obstruction score. Meteorological data collected for the relevant time period were: air temperature, humidity, atmospheric pressure, visibility, wind speed and precipitation. No significant differences in seasonal distribution of pulmonary embolism episodes were observed. Episodes of more severe pulmonary embolism were preceded by periods of lower atmospheric pressure (1,016.35 hPA for group H, vs. 1,016.35 hPa for group L, p = 0.022). No significant relations between other meteorological factors and severity of PE were observed. The reported finding shows the need of further research on the nature of meteorological factors influence on the course of pulmonary embolism, which should be analyzed not ony regarding the frequency, but also severity of PE episodes. PMID:21736277

  5. Effect of graft preservation and acute rejection on hypoxia-inducible factor-1 in rat cardiac allografts.

    PubMed

    Keränen, M A I; Nykänen, A I; Krebs, R; Tuuminen, R; Sandelin, H; Koskinen, P K; Lemström, K B

    2006-12-01

    Hypoxia plays an integral part in cardiac transplantation as prolonged graft preservation is an individual risk factor for the development of cardiac allograft vasculopathy (CAV). In this study we characterized the role of hypoxia-inducible factor-1 (HIF-1) during prolonged graft preservation, ischemia-reperfusion (I/R), acute rejection, and chronic rejection. Heart transplantations were performed from Dark Agouti (DA) to Wister-Furth (allo) or DA to DA (syn) rats, without immunosuppression (acute rejection model, harvested at day 5) or with cyclosporine (chronic rejection model, harvested at day 60). To study the effect of preservation on HIF-1 regulation, normal DA hearts were subjected to different cold ischemia times with or without 45 minutes of additional warm ischemia. The role of I/R was studied by harvesting syngrafts at different time points after reperfusion. Real-time reverse-transcriptase polymerase chain reaction quantified total HIF-1 mRNA, while enzyme-linked immunosorbent assay and immunohistochemistry quantified and localized HIF-1 protein. Our results show that HIF-1 nuclear immunoreactivity is increased during graft preservation and I/R leads to loss of nuclear HIF-1 immunoreactivity. Acute rejection induced HIF-1 in mRNA level. Our findings thus indicated that HIF-1 is activated during transplantation and suggested that manipulation of the HIF-1 pathway might reveal new therapeutic options to manage CAV. PMID:17175275

  6. Oxidative stress response to acute hypobaric hypoxia and its association with indirect measurement of increased intracranial pressure: a field study.

    PubMed

    Strapazzon, Giacomo; Malacrida, Sandro; Vezzoli, Alessandra; Dal Cappello, Tomas; Falla, Marika; Lochner, Piergiorgio; Moretti, Sarah; Procter, Emily; Brugger, Hermann; Mrakic-Sposta, Simona

    2016-01-01

    High altitude is the most intriguing natural laboratory to study human physiological response to hypoxic conditions. In this study, we investigated changes in reactive oxygen species (ROS) and oxidative stress biomarkers during exposure to hypobaric hypoxia in 16 lowlanders. Moreover, we looked at the potential relationship between ROS related cellular damage and optic nerve sheath diameter (ONSD) as an indirect measurement of intracranial pressure. Baseline measurement of clinical signs and symptoms, biological samples and ultrasonography were assessed at 262 m and after passive ascent to 3830 m (9, 24 and 72 h). After 24 h the imbalance between ROS production (+141%) and scavenging (-41%) reflected an increase in oxidative stress related damage of 50-85%. ONSD concurrently increased, but regression analysis did not infer a causal relationship between oxidative stress biomarkers and changes in ONSD. These results provide new insight regarding ROS homeostasis and potential pathophysiological mechanisms of acute exposure to hypobaric hypoxia, plus other disease states associated with oxidative-stress damage as a result of tissue hypoxia. PMID:27579527

  7. Oxidative stress response to acute hypobaric hypoxia and its association with indirect measurement of increased intracranial pressure: a field study

    PubMed Central

    Strapazzon, Giacomo; Malacrida, Sandro; Vezzoli, Alessandra; Dal Cappello, Tomas; Falla, Marika; Lochner, Piergiorgio; Moretti, Sarah; Procter, Emily; Brugger, Hermann; Mrakic-Sposta, Simona

    2016-01-01

    High altitude is the most intriguing natural laboratory to study human physiological response to hypoxic conditions. In this study, we investigated changes in reactive oxygen species (ROS) and oxidative stress biomarkers during exposure to hypobaric hypoxia in 16 lowlanders. Moreover, we looked at the potential relationship between ROS related cellular damage and optic nerve sheath diameter (ONSD) as an indirect measurement of intracranial pressure. Baseline measurement of clinical signs and symptoms, biological samples and ultrasonography were assessed at 262 m and after passive ascent to 3830 m (9, 24 and 72 h). After 24 h the imbalance between ROS production (+141%) and scavenging (−41%) reflected an increase in oxidative stress related damage of 50–85%. ONSD concurrently increased, but regression analysis did not infer a causal relationship between oxidative stress biomarkers and changes in ONSD. These results provide new insight regarding ROS homeostasis and potential pathophysiological mechanisms of acute exposure to hypobaric hypoxia, plus other disease states associated with oxidative-stress damage as a result of tissue hypoxia. PMID:27579527

  8. NW Black Sea ecosystems recovery from former severe seasonal hypoxia and effect on macrofauna

    NASA Astrophysics Data System (ADS)

    Gomoiu, Marian-Traian; Begun, Tatiana; Teaca, Adrian

    2013-04-01

    The benthos researches carried out in the last decade on the NW Black Sea shelf established the transitional process of the bottom communities, from the severe disturbed state resulted from seasonal hypoxia of high eutrophication from 1970-2000 period towards a new state. The authors, with their expertise achieved in the framework of several national and EU FP6&7 projects (SESAME, HYPOX, PERSEUS), analyzing more than 600 quantitative samples, consider the benthic associations influenced mainly by the Danube River discharge being characterized as follows: • decrease in the specific diversity (e.g. Mollusca - from 170 species in the 1960s - 1970s to 70 species in the present in NW Black Sea); • loss or diminishing of some habitat areas (typical habitat with Zostera, Phyllophora, Cystoseira, Barnea, Donacilla etc.); • increase in the numeric abundance and biomass of some specific benthic populations (Melinna, Alitta, Dipolydora etc.); • loss or reduction of some specific populations (Abra prismatica, Spisula subtruncata, Chamelia gallina etc.); • replacement of some strong and quite large benthic populations by metapopulation of small extension; • diminution of the biofilter strength by reduction of the filter - feeder populations; • qualitative and quantitative worsening of benthic biological resources, especially molluscs - forms playing an important ecological part and with great economic importance (mussel Mytilus galloprovincialis, soft-shell clam Mya arenaria, veined rapa whelk Rapana venosa); • thriving of opportunistic forms (especially worms populations causing sediment bioturbation - Melinna palmata, Heteromastus filiformis) and, temporarily, some exotic species recently pervading Black Sea (Mya, Anadara, Rapana etc.); • great quantitative fluctuations of all benthic populations; • occurrence of some weak sing of ecosystem recovery. However, recovery of the benthic ecosystem appears to be less certain although an improvement on

  9. Daily acute intermittent hypoxia elicits functional recovery of diaphragm and inspiratory intercostal muscle activity after acute cervical spinal injury

    PubMed Central

    Navarrete-Opazo, A.; Vinit, S; Dougherty, B.J.; Mitchell, G.S.

    2015-01-01

    A major cause of mortality after spinal cord injury is respiratory failure. In normal rats, acute intermittent hypoxia (AIH) induces respiratory motor plasticity, expressed as diaphragm (Dia) and second external intercostal (T2 EIC) long-term facilitation (LTF). Dia (not T2 EIC) LTF is enhanced by systemic adenosine 2A (A2a) receptor inhibition in normal rats. We investigated the respective contributions of Dia and T2 EIC to daily AIH-induced functional recovery of breathing capacity with/without A2a receptor antagonist (KW6002, i.p.) following C2 hemisection (C2HS). Rats received daily AIH (dAIH: 10, 5-min episodes, 10.5% O2; 5-min normoxic intervals; 7 successive days beginning 7 days post-C2HS) or daily normoxia (dNx) with/without KW6002, followed by weekly (reminder) presentations for 8 weeks. Ventilation and EMGs from bilateral diaphragm and T2 EIC muscles were measured with room air breathing (21% O2) and maximum chemoreceptor stimulation (MCS: 7% CO2, 10.5% O2). dAIH increased tidal volume (Vt) in C2HS rats breathing room air (dAIH + vehicle: 0.47 ± 0.02, dNx + vehicle: 0.40 ± 0.01ml/100 g; p<0.05) and MCS (dAIH + vehicle: 0.83 ± 0.01, dNx + vehicle: 0.73 ± 0.01ml/100g; p<0.001); KW6002 had no significant effect. dAIH enhanced contralateral (uninjured) diaphragm EMG activity, an effect attenuated by KW6002, during room air breathing and MCS (p<0.05). Although dAIH enhanced contralateral T2 EIC EMG activity during room air breathing, KW6002 had no effect. dAIH had no statistically significant effects on diaphragm or T2 EIC EMG activity ipsilateral to injury. Thus, two weeks post-C2HS: 1) dAIH enhances breathing capacity by effects on contralateral diaphragm and T2 EIC activity; and 2) dAIH-induced recovery is A2a dependent in diaphragm, but not T2 EIC. Daily AIH may be a useful in promoting functional recovery of breathing capacity after cervical spinal injury, but A2a receptor antagonists (eg. caffeine) may undermine its effectiveness shortly after

  10. Alcohol abuse-related severe acute pancreatitis with rhabdomyolysis complications

    PubMed Central

    SU, MAO-SHENG; JIANG, YING; YAN, XIAO-YUAN HU; ZHAO, QING-HUA; LIU, ZHI-WEI; ZHANG, WEN-ZHI; HE, LEI

    2013-01-01

    Non-traumatic rhabdomyolysis is a rare complication of acute pancreatitis. One of the major risk factors of both acute pancreatitis and rhabdomyolysis is alcohol abuse. However, only a few studies have reported the prognosis and association of severe acute pancreatitis (SAP) and rhabdomyolysis in alcohol abuse patients. In the present study, we report two cases presenting with SAP complicated by rhabdomyolysis following high-dose alcohol intake. The disease onset, clinical manifestations, laboratory data, diagnosis and treatment procedure of each patient were recorded, and the association with rhabdomyolysis was analyzed. Alcohol consumption was the most predominant cause of SAP and rhabdomyolysis in these patients. SAP-related rhabdomyolysis was primarily induced by the toxicity associated with pancreatic necrosis. The laboratory tests revealed that the concentration of serum creatine kinase (CK) and myoglobin increased and acute renal failure symptoms were present, which provided an exact diagnosis for SAP-induced rhabdomyolysis. Rhabdomyolysis and subsequent hypermyoglobinuria severely impaired kidney function and aggravated hypocalcemia. The therapy of early stage SAP complicated by rhabdomyolysis involved liquid resuscitation support. When first stage treatment fails, blood purification should be performed immediately. Both patients developed multiple organ failure (MOF) and succumbed to the disease. Considering the two cases presented, we conclude that alcohol-related SAP complicated by rhabdomyolysis may have a poor clinical prognosis. PMID:23251265

  11. A severe case of acute exogenous lipoid pneumonia treated with systemic corticosteroid.

    PubMed

    Yasui, Hideki; Yokomura, Koshi; Suda, Takafumi

    2016-01-01

    Acute exogenous lipoid pneumonia is a rare disorder in adults. A treatment of choice for lipoid pneumonia has not been established, and systemic corticosteroid use remains controversial. We report the case of a 32-year-old man with schizophrenia who presented with kerosene-induced acute exogenous lipoid pneumonia that was treated with a systemic corticosteroid. In this case, supportive therapy did not improve the patient's condition, so systemic corticosteroid therapy was commenced four days after he ingested the kerosene. After corticosteroid commencement, the patient's symptoms and hypoxia improved within a few days. Although some radiological characteristics of this disorder have been reported previously, the process of radiological improvement of exogenous lipoid pneumonia is not well known. In this case, computed tomography findings changed dramatically after corticosteroid therapy was initiated. Extensive bilateral consolidations that were observed on admission improved. Although pneumatoceles developed two weeks after corticosteroid commencement, they were nearly gone after two months of the treatment. While corticosteroid therapy is not suitable for all cases, it should be considered for severe or refractory cases. PMID:27222789

  12. A severe case of acute exogenous lipoid pneumonia treated with systemic corticosteroid

    PubMed Central

    Yasui, Hideki; Yokomura, Koshi; Suda, Takafumi

    2016-01-01

    Acute exogenous lipoid pneumonia is a rare disorder in adults. A treatment of choice for lipoid pneumonia has not been established, and systemic corticosteroid use remains controversial. We report the case of a 32-year-old man with schizophrenia who presented with kerosene-induced acute exogenous lipoid pneumonia that was treated with a systemic corticosteroid. In this case, supportive therapy did not improve the patient's condition, so systemic corticosteroid therapy was commenced four days after he ingested the kerosene. After corticosteroid commencement, the patient's symptoms and hypoxia improved within a few days. Although some radiological characteristics of this disorder have been reported previously, the process of radiological improvement of exogenous lipoid pneumonia is not well known. In this case, computed tomography findings changed dramatically after corticosteroid therapy was initiated. Extensive bilateral consolidations that were observed on admission improved. Although pneumatoceles developed two weeks after corticosteroid commencement, they were nearly gone after two months of the treatment. While corticosteroid therapy is not suitable for all cases, it should be considered for severe or refractory cases. PMID:27222789

  13. Acute hypoxia modifies cAMP levels induced by inhibitors of phosphodiesterase-4 in rat carotid bodies, carotid arteries and superior cervical ganglia

    PubMed Central

    Nunes, Ana R; Batuca, Joana R; Monteiro, Emília C

    2010-01-01

    Background and purpose: Phosphodiesterase (PDE) inhibitors are useful to treat hypoxia-related diseases and are used in experiments studying the effects of oxygen on 3′-5′-cyclic adenosine monophosphate (cAMP) production. We studied the effects of acute hypoxia on cAMP accumulation induced by PDE inhibitors in oxygen-specific chemosensors, the carotid bodies (CBs) and in non-chemosensitive CB-related structures: carotid arteries (CAs) and superior cervical ganglia (SCG). Experimental approach: Concentration–response curves for the effects of a non-specific PDE inhibitor [isobutylmethylxanthine (IBMX) ], PDE4 selective inhibitors (rolipram, Ro 20-1724) and a PDE2 selective inhibitor (erythro-9-(2-hydroxy-3-nonyl)adenine) on cAMP levels were obtained in normoxic (20% O2/5% CO2) or hypoxic (5% O2/5% CO2) conditions. Key results: Responses to the PDE inhibitors were compatible with the presence of PDE4 in rat CBs, CAs and SCG but in the absence of PDE2 in CAs and CBs. Acute hypoxia enhanced the effects of IBMX and PDE4 inhibitors on cAMP accumulation in CAs and CBs. In SCG, acute hypoxia reduced cAMP accumulation induced by all the four PDE inhibitors tested. Differences between the effects of Ro 20-1724 and rolipram on cAMP were found in CAs and CBs during hypoxia. Conclusions and implications: The effects of PDE4 inhibitors could be potentiated or inhibited by acute hypoxia depending on the PDE isoforms of the tissue. The similarities between the characterization of PDE4 inhibitors at the CBs and CAs, under normoxia and hypoxia, did not support a specific role for cAMP in the oxygen-sensing machinery at the CB and suggested that no direct CB-mediated, hyperventilatory, adverse effects would be expected with administration of PDE4 inhibitors. PMID:20082613

  14. Size restricted silymarin suspension evokes integrated adaptive response against acute hypoxia exposure in rat lung.

    PubMed

    Paul, Subhojit; Arya, Aditya; Gangwar, Anamika; Bhargava, Kalpana; Ahmad, Yasmin

    2016-07-01

    Despite its extraordinary antioxidant capacity, the clinical usage of silymarin has remained restricted to amelioration of hepatic pathology. Perhaps its low bioavailability and uneven bio-distribution, owing to its poor aqueous solubility, are two main causes that have dampened the clinical applicability and scope of this preparation. We took these two challenges and suggested an unexplored application of silymarin. Apart from liver, two of the most susceptible vital organs at the highest risk of oxidative stress are brain and lung, especially during reduced oxygen saturation (hypoxia) at anatomical level. Hypoxia causes excess generation of radicals primarily in the lungs as it is the first organ at the interphase of atmosphere and organism making it the most prone and vulnerable to oxidative stress and the first responder against hypobaric hypoxia. As our first objective, we improved the silymarin formulation by restricting its size to the lower threshold and then successfully tested the prophylactic and therapeutic action in rat lung challenged with simulated hypobaric hypoxia. After dose optimization, we observed that 50mg/kg BW silymarin as size restricted and homogenous aqueous suspension successfully minimized the reactive oxygen species and augmented the antioxidant defense by significant upregulation of catalase and superoxide dismutase and reduced glutathione. Moreover, the well-established hypoxia markers and proteins related to hypoxia adaptability, hif1a and VEGF were differentially regulated conferring significant reduction in the inflammation caused by hypobaric hypoxia. We therefore report,the unexplored potential benefits of silymarin for preventing high altitude associated pathophysiology further paving its road to clinical trials. PMID:27105952

  15. A microfluidic system for studying the behavior of zebrafish larvae under acute hypoxia.

    PubMed

    Erickstad, Michael; Hale, Laura A; Chalasani, Sreekanth H; Groisman, Alex

    2015-02-01

    Oxygen is essential for metabolism of animals and is a vital component of their natural habitats. Hypoxic conditions in tissue, when oxygen levels are lower than normal, change a variety of cellular processes, while environmental hypoxia can have physiological and behavioral effects on the whole animal. Larval zebrafish respond to oxygen deprivation with a characteristic set of physiological changes and motor behaviors, making them a convenient vertebrate model to study hypoxia responses. However, to date, hypoxia studies in zebrafish are limited by the existing experimental setups, which only impose hypoxia on a scale of minutes to hours. Here, we present a microfluidic system, which makes it possible to expose spatially confined unanesthetized zebrafish larvae to a broad range of hypoxic and normoxic conditions and to switch between different oxygen concentrations in the medium around the larvae on a 2 second timescale. We used the system to observe different behavioral responses of zebrafish larvae to three levels of rapidly imposed hypoxia. Larvae increased their rate of body movements in response to the strongest hypoxia and increased their rate of pectoral fin beats in response to all levels of hypoxia. Importantly, the behavior of the larvae changed within 15 seconds of the changes in the oxygen content of the medium. The proposed experimental system can be used to study the behavior of zebrafish larvae or other aquatic organisms exposed to other water-dissolved gasses or to different temporal patterns of oxygen concentration. This system can also potentially be used for testing the effects of genetic modifications and small molecule drugs and for probing neural mechanisms underlying various behaviors. PMID:25490410

  16. Early severe acute pancreatitis: characteristics of a new subgroup.

    PubMed

    Isenmann, R; Rau, B; Beger, H G

    2001-04-01

    This study focuses on patients with severe acute pancreatitis complicated by organ failure within the initial phase of the disease. Data of 158 patients with severe acute pancreatitis (SAP) admitted to hospital within 72 hours after onset of symptoms were prospectively documented and analyzed for the occurrence of early severe acute pancreatitis (ESAP). ESAP was defined as presence of organ failure (OF) at admission. Forty-seven (30%) patients had ESAP, compared with 111 patients without OF (SAP group). In a multivariate analysis, the main factor predisposing to ESAP was the presence of extended pancreatic necrosis (odds ratio, 3.8), whereas biliary pancreatitis was associated with a slightly lower risk compared with alcoholic pancreatitis (odds ratio, 0.34). Compared with SAP, patients with ESAP more frequently developed intractable organ failure, which posed the indication for surgical treatment. Surgical necrosectomy due to progressive OF had to be performed in 89% of the ESAP patients and in 60% of the SAP patients. The incidence of infected pancreatic necrosis did not differ between both groups (23 vs. 21%). Mortality was significantly higher in ESAP (42 vs. 14%; p = 0.0003). ESAP is characterized by the presence of extended pancreatic necrosis and a complicated clinical course. Intractable organ failure is a frequent finding. Given the poor prognosis of ESAP, these patients should be treated in specialized intensive care units. PMID:11291929

  17. [Individual typological features of EEG response in the sportsman to acute hypoxia].

    PubMed

    Balioz, N V; Krivoshchekov, S G

    2012-01-01

    The paper investigated variability of individual EEG parametres: frequency of the maximum peak, width of a range and depth of reaction desynchronization (reduction alpha-rhythm of EEG at opening of eyes) in slowly increasing hypoxia from 20.9% to 10%-s' O2 of the sportsman with various types of physical activity and features of temperament. There were investigated 24 first-class athletes (11 swimmers, 13 skiers) aged 18-26 years. It is shown that dynamics of EEG rhythms during hypoxia, unlike normoxia, characterised by instability of spectral structure and phase during time of hypoxia test. It is established, that individual typological features (typology of nervous system) influence EEG response during hypoxic test. The negative relations between a psychological construct "endurance" for questionnaire (FCB-Ti) and feature alpha-rhythm EEG during hypoxia test are shown. The type of physical training and re-structuring pattern of breath (phenotypic adaptation) modulates sensitivity of brain structures to hypoxia which is reflected in dynamics alpha-rhythm of EEG in hypoxic conditions. PMID:23101237

  18. [Effects of acute hypobaric hypoxia and exhaustive exercise on AMP-activated protein kinase phosphorylation in rat skeletal muscle].

    PubMed

    Yang, Tao; Huang, Qing-Yuan; Shan, Fa-Bo; Guan, Li-Bin; Cai, Ming-Chun

    2012-04-25

    The present study was aimed to explore the changes of phosphorylated AMP-activated protein kinase (pAMPK) level in skeletal muscle after exposure to acute hypobaric hypoxia and exhaustive exercise. Thirty-two male Sprague-Dawley (SD) rats were randomly divided into sea level and high altitude groups. The rats in high altitude group were submitted to simulated 5 000 m of high altitude in a hypobaric chamber for 24 h, and sea level group was maintained at normal conditions. All the rats were subjected to exhaustive swimming exercise. The exhaustion time was recorded. Before and after the exercise, blood lactate and glycogen content in skeletal muscle were determined; AMPK and pAMPK levels in skeletal muscle were detected by Western blot. The results showed that the exhaustion time was significantly decreased after exposure to high altitude. At the moment of exhaustion, high altitude group had lower blood lactate concentration and higher surplus glycogen content in gastrocnemius compared with sea level group. Exhaustive exercise significantly increased the pAMPK/AMPK ratio in rat skeletal muscles from both sea level and high altitude groups. However, high altitude group showed lower pAMPK/AMPK ratio after exhaustion compared to sea level group. These results suggest that, after exposure to acute hypobaric hypoxia, the decrement in exercise capacity may not be due to running out of glycogen, accumulation of lactate or disturbance in energy status in skeletal muscle. PMID:22513470

  19. Update: Outbreak of severe acute respiratory syndrome--worldwide, 2003.

    PubMed

    2003-03-28

    CDC continues to support the World Health Organization (WHO) in the investigation of a multicountry outbreak of unexplained atypical pneumonia referred to as severe acute respiratory syndrome (SARS). This report includes summaries of the epidemiologic investigations and public health responses in several affected locations where CDC is collaborating with international and national health authorities. This report also describes an unusual cluster of cases associated with a hotel in Hong Kong and identifies the potential etiologic agent of SARS. Epidemiologic and laboratory investigations of SAPS are ongoing. PMID:12680518

  20. Severe acute pancreatitis: Pathogenetic aspects and prognostic factors

    PubMed Central

    Mofleh, Ibrahim A Al

    2008-01-01

    Approximately 20% of patients with acute pancreatitis develop a severe disease associated with complications and high risk of mortality. The purpose of this study is to review pathogenesis and prognostic factors of severe acute pancreatitis (SAP). An extensive medline search was undertaken with focusing on pathogenesis, complications and prognostic evaluation of SAP. Cytokines and other inflammatory markers play a major role in the pathogenesis and course of SAP and can be used as prognostic markers in its early phase. Other markers such as simple prognostic scores have been found to be as effective as multifactorial scoring systems (MFSS) at 48 h with the advantage of simplicity, efficacy, low cost, accuracy and early prediction of SAP. Recently, several laboratory markers including hematocrit, blood urea nitrogen (BUN), creatinine, matrix metalloproteinase-9 (MMP-9) and serum amyloid A (SAA) have been used as early predictors of severity within the first 24 h. The last few years have witnessed a tremendous progress in understanding the pathogenesis and predicting the outcome of SAP. In this review we classified the prognostic markers into predictors of severity, pancreatic necrosis (PN), infected PN (IPN) and mortality. PMID:18205255

  1. Ascites fluid in severe acute pancreatitis: from pathophysiology to therapy.

    PubMed

    Dugernier, T; Laterre, P F; Reynaert, M S

    2000-01-01

    Several pathophysiological mechanisms are involved in the development of the inflammatory necrotizing process that takes place in the retroperitoneal area during the early phase of acute pancreatitis. They include premature intraglandular activation of pancreatic proenzymes (zymogens) and in particular trypsin, early microcirculatory impairment with subsequent ischaemia/reperfusion and overstimulation of immune effector cells. Although intra-acinar or interstitial activation of trypsinogen is most probably the trigger of acute pancreatitis, in recent years much emphasis has been put on the role of leukocytes. Based on numerous experimental and human data several pro-inflammatory mediators including cytokines, arachidonic acid derivatives, activated oxygen species and proteases are released locally by overactivated neutrophils and monocytes/macrophages among other cells. They are now believed to play a central role in the development of pancreatic necrosis and, once they gain access to the systemic circulation, in the emergence of early multisystem organ failure. However the sequential and relative contribution of each of these 3 pathophysiological mechanisms remain controversial and the precise identification of the mediators incriminated in local and remote tissue injury is still awaited. Severe acute pancreatitis still carries a mortality of 20% to 30%. With advances in intensive care management 80% of the deaths occur somewhat late in the attack due to infected pancreatic necrosis. Nevertheless early remote organ failures still remain a lifethreatening condition for most of these patients. A peritoneal exudate rich in activated lipolytic and proteolytic enzymes, vasoactive substances and several other pro-inflammatory mediators collect in over 60% of the patients with severe acute pancreatitis. On the basis of favourable animal experiments early percutaneous or surgical peritoneal lavage with or without the addition of antiproteases has been carried out in human

  2. Severe acute malnutrition during emergencies: burden management, and gaps.

    PubMed

    Bahwere, Paluku

    2014-06-01

    Natural and man-made disasters, including floods, droughts, earthquakes, and armed conflicts, create nutrition crises. Unfortunately, the frequency and severity of such disasters have been increasing since the beginning of the 20th century, and their contribution to the burden of acute malnutrition is increasing every year. However, their contribution to the burden of acute malnutrition is underrecognized due to the ways in which global statistics are built and causes of death are reported. Fortunately, the success of the current protocol for treatment of severe acute malnutrition (SAM) and the integrated approach to treatment has created a momentum allowing expanded coverage of treatment of SAM, especially in humanitarian emergency contexts. For this progress to be maintained and accelerated, changes in nutrition information systems at the national and global levels are needed, and the persisting barriers to the expansion and integration of treatment of SAM into routine health systems need to be removed. Emergency funding approaches and objectives have to include sustaining and amplifying the achievements of the short-term palliative interventions. Nutrition programs implemented in emergency contexts have the capacity to contribute to answering priority research questions, and this capacity should be more optimally utilized. PMID:25069293

  3. Acute, Severe Cryptosporidiosis in an Immunocompetent Pediatric Patient

    PubMed Central

    Tallant, Caitlin; Huddleston, Patrick; Alshanberi, Asim

    2016-01-01

    Severe diarrheal illness in children can be attributed to a number of different microbiological agents. Without appropriate microbiological testing of stool samples, patients who present with multiple days of severe diarrhea might have a delay in proper diagnosis and treatment. Here, we report a case of an immunocompetent pediatric patient presenting with acute cryptosporidiosis. Humans and bovine species are known hosts of cryptosporidium and several studies have evaluated the zoonotic transmission of cryptosporidium from cattle to humans. Adding diagnostic tests for cryptosporidium like Ziehl-Neelsen staining of stool or fecal rapid antigen detection techniques should be considered in the workup of patients presenting with undifferentiated, severe diarrheal illness, especially in those who have close contact with livestock. PMID:27478580

  4. Hypoxia-induced alveolar epithelial-mesenchymal transition requires mitochondrial ROS and hypoxia-inducible factor 1

    PubMed Central

    Zhou, Guofei; Dada, Laura A.; Wu, Minghua; Kelly, Aileen; Trejo, Humberto; Zhou, Qiyuan; Varga, John

    2009-01-01

    Patients with acute lung injury develop hypoxia, which may lead to lung dysfunction and aberrant tissue repair. Recent studies have suggested that epithelial-mesenchymal transition (EMT) contributes to pulmonary fibrosis. We sought to determine whether hypoxia induces EMT in alveolar epithelial cells (AEC). We found that hypoxia induced the expression of α-smooth muscle actin (α-SMA) and vimentin and decreased the expression of E-cadherin in transformed and primary human, rat, and mouse AEC, suggesting that hypoxia induces EMT in AEC. Both severe hypoxia and moderate hypoxia induced EMT. The reactive oxygen species (ROS) scavenger Euk-134 prevented hypoxia-induced EMT. Moreover, hypoxia-induced expression of α-SMA and vimentin was prevented in mitochondria-deficient ρ0 cells, which are incapable of ROS production during hypoxia. CoCl2 and dimethyloxaloylglycine, two compounds that stabilize hypoxia-inducible factor (HIF)-α under normoxia, failed to induce α-SMA expression in AEC. Furthermore, overexpression of constitutively active HIF-1α did not induce α-SMA. However, loss of HIF-1α or HIF-2α abolished induction of α-SMA mRNA during hypoxia. Hypoxia increased the levels of transforming growth factor (TGF)-β1, and preincubation of AEC with SB431542, an inhibitor of the TGF-β1 type I receptor kinase, prevented the hypoxia-induced EMT, suggesting that the process was TGF-β1 dependent. Furthermore, both ROS and HIF-α were necessary for hypoxia-induced TGF-β1 upregulation. Accordingly, we have provided evidence that hypoxia induces EMT of AEC through mitochondrial ROS, HIF, and endogenous TGF-β1 signaling. PMID:19801454

  5. Acute fatty liver of pregnancy associated with severe acute pancreatitis: A case report

    PubMed Central

    de Oliveira, Cássio Vieira; Moreira, Alecsandro; Baima, Julio P; Franzoni, Leticia de C; Lima, Talles B; Yamashiro, Fabio da S; Coelho, Kunie Yabuki Rabelo; Sassaki, Ligia Y; Caramori, Carlos Antonio; Romeiro, Fernando G; Silva, Giovanni F

    2014-01-01

    Acute fatty liver of pregnancy is a rare disease that affects women in the third trimester of pregnancy. Although infrequent, the disease can cause maternal mortality. The diagnosis is not always clear until the pregnancy is terminated, and significant complications, such as acute pancreatitis, can occur. Pancreatic involvement typically only occurs in severe cases after the development of hepatic and renal impairment. To date, little knowledge is available regarding how the disease causes pancreatitis. Treatment involves supportive measures and pregnancy interruption. In this report, we describe a case of a previously healthy 26-year-old woman at a gestational age of 27 wk and 6 d who was admitted with severe abdominal pain and vomiting. This case illustrates the clinical and laboratory overlap between acute fatty liver of pregnancy and pancreatitis, highlighting the difficulties in differentiating each disease. Furthermore, the hypothesis for this overlapping is presented, and the therapeutic options are discussed. PMID:25068005

  6. Rapid regulation of blood parameters under acute hypoxia in the Amazonian fish Prochilodus nigricans.

    PubMed

    Val, Adalberto Luis; Gomes, Katia Regina Maruyama; de Almeida-Val, Vera Maria Fonseca

    2015-06-01

    Prochilodus nigricans, locally known as curimatã, is an Amazonian commercial fish that endures adverse environmental conditions, in particular low dissolved oxygen, during its migration. Poorer environmental conditions are expected in the near future. Prochilodus nigricans overcomes current seasonal and diurnal changes in dissolved oxygen by adjusting erythrocytic levels of ATP and GTP, modulators of Hb-O2 affinity. Will this fish species be endangered under more extreme environmental conditions as hypoxia and acidification tend to occur in a shorter period of time? As P. nigricans does not exhibit any apparent morphological alterations to exploit the air-water interface, it must rely on fast adjustments of blood properties. To investigate this aspect, basic hematology indices, pHe, pHi, plasma lactate, erythrocytic levels of ATP and GTP and functional properties of the hemolysate of P. nigricans were analyzed over a period of 6h in hypoxia and subsequent recovery in normoxia. The levels of erythrocytic GTP were four times higher than ATP and were reduced to ¼ of the original level after 3h under hypoxia. Erythrocytic levels of ATP were unaffected over the experimental period. All other analyzed blood parameters exhibited a time-course change in animals under hypoxia and returned to normoxic levels. Considering the hemolysate functional properties and the ability to regulate the above mentioned blood characteristics, P. nigricans is able to endure short-term changes in dissolved oxygen. PMID:25737030

  7. Effect of acute hypoxia on respiratory muscle fatigue in healthy humans

    PubMed Central

    2010-01-01

    Background Greater diaphragm fatigue has been reported after hypoxic versus normoxic exercise, but whether this is due to increased ventilation and therefore work of breathing or reduced blood oxygenation per se remains unclear. Hence, we assessed the effect of different blood oxygenation level on isolated hyperpnoea-induced inspiratory and expiratory muscle fatigue. Methods Twelve healthy males performed three 15-min isocapnic hyperpnoea tests (85% of maximum voluntary ventilation with controlled breathing pattern) in normoxic, hypoxic (SpO2 = 80%) and hyperoxic (FiO2 = 0.60) conditions, in a random order. Before, immediately after and 30 min after hyperpnoea, transdiaphragmatic pressure (Pdi,tw ) was measured during cervical magnetic stimulation to assess diaphragm contractility, and gastric pressure (Pga,tw ) was measured during thoracic magnetic stimulation to assess abdominal muscle contractility. Two-way analysis of variance (time x condition) was used to compare hyperpnoea-induced respiratory muscle fatigue between conditions. Results Hypoxia enhanced hyperpnoea-induced Pdi,tw and Pga,tw reductions both immediately after hyperpnoea (Pdi,tw : normoxia -22 ± 7% vs hypoxia -34 ± 8% vs hyperoxia -21 ± 8%; Pga,tw : normoxia -17 ± 7% vs hypoxia -26 ± 10% vs hyperoxia -16 ± 11%; all P < 0.05) and after 30 min of recovery (Pdi,tw : normoxia -10 ± 7% vs hypoxia -16 ± 8% vs hyperoxia -8 ± 7%; Pga,tw : normoxia -13 ± 6% vs hypoxia -21 ± 9% vs hyperoxia -12 ± 12%; all P < 0.05). No significant difference in Pdi,tw or Pga,tw reductions was observed between normoxic and hyperoxic conditions. Also, heart rate and blood lactate concentration during hyperpnoea were higher in hypoxia compared to normoxia and hyperoxia. Conclusions These results demonstrate that hypoxia exacerbates both diaphragm and abdominal muscle fatigability. These results emphasize the potential role of respiratory muscle fatigue in exercise performance limitation under conditions coupling

  8. Severe acute measles pneumonitis: virus isolation in bronchoalveolar lavage fluid.

    PubMed

    Suter, Cosima; Buergi, Urs; Eigenmann, Katja; Franzen, Daniel

    2015-01-01

    In the past few years, several endemic outbreaks of measles have been recognised, not only in children but also in adults, with severe and, occasionally, even fatal complications, possibly due to delayed diagnosis of the disease in adult medicine and decreasing vaccination rates. Furthermore, the treatment consists of supportive measures only. We present a case of severe measles pneumonitis in a 42-year-old man, a travel returnee, proven by direct virus isolation with PCR from bronchoalveolar lavage fluid. CT findings and pulmonary function testing revealed features of obstructive bronchiolitis; the patient was successfully treated with corticosteroids. He fully recovered, and lung function measurement returned to normal values. We conclude that acute measles can present as obstructive bronchiolitis and may be successfully treated with corticosteroids. PMID:26508116

  9. Survival and function of mesenchymal stem cells (MSCs) depend on glucose to overcome exposure to long-term, severe and continuous hypoxia

    PubMed Central

    Deschepper, M; Oudina, K; David, B; Myrtil, V; Collet, C; Bensidhoum, M; Logeart-Avramoglou, D; Petite, H

    2011-01-01

    Abstract Use of mesenchymal stem cells (MSCs) has emerged as a potential new treatment for various diseases but has generated marginally successful results. A consistent finding of most studies is massive death of transplanted cells. The present study examined the respective roles of glucose and continuous severe hypoxia on MSC viability and function with respect to bone tissue engineering. We hereby demonstrate for the first time that MSCs survive exposure to long-term (12 days), severe (pO2 < 1.5 mmHg) hypoxia, provided glucose is available. To this end, an in vitro model that mimics the hypoxic environment and cell-driven metabolic changes encountered by grafted sheep cells was established. In this model, the hallmarks of hypoxia (low pO2, hypoxia inducible factor-1α expression and anaerobic metabolism) were present. When conditions switched from hypoxic (low pO2) to ischemic (low pO2 and glucose depletion), MSCs exhibited shrinking, decreased cell viability and ATP content due to complete exhaustion of glucose at day 6; these results provided evidence that ischemia led to the observed massive cell death. Moreover, MSCs exposed to severe, continuous hypoxia, but without any glucose shortage, remained viable and maintained both their in vitro proliferative ability after simulation with blood reperfusion at day 12 and their in vivo osteogenic ability. These findings challenge the traditional view according to which severe hypoxia per se is responsible for the massive MSC death observed upon transplantation of these cells and provide evidence that MSCs are able to withstand exposure to severe, continuous hypoxia provided that a glucose supply is available. PMID:20716129

  10. Acute Beetroot Juice Supplementation Does Not Improve Cycling Performance in Normoxia or Moderate Hypoxia.

    PubMed

    MacLeod, Kristin E; Nugent, Sean F; Barr, Susan I; Koehle, Michael S; Sporer, Benjamin C; MacInnis, Martin J

    2015-08-01

    Beetroot juice (BR) has been shown to lower the oxygen cost of exercise in normoxia and may have similar effects in hypoxia. We investigated the effect of BR on steady-state exercise economy and 10-km time trial (TT) performance in normoxia and moderate hypoxia (simulated altitude: ~2500 m). Eleven trained male cyclists (VO 2peak ≥ 60 ml · kg(-1) · min(-1)) completed four exercise trials. Two hours before exercise, subjects consumed 70 mL BR (~6 mmol nitrate) or placebo (nitrate-depleted BR) in a randomized, double-blind manner. Subjects then completed a 15-min self-selected cycling warm-up, a 15-min steady-state exercise bout at 50% maximum power output, and a 10-km time trial (TT) in either normoxia or hypoxia. Environmental conditions were randomized and single-blind. BR supplementation increased plasma nitrate concentration and fraction of exhaled nitric oxide relative to PL (p < .05 for both comparisons). Economy at 50% power output was similar in hypoxic and normoxic conditions (p > .05), but mean power output was greater in the normoxic TT relative to the hypoxic TT (p < .05). BR did not affect economy, steady-state SpO2, mean power output, or 10-km TT completion time relative to placebo in either normoxia or hypoxia (p > .05 in all comparisons). In conclusion, BR did not lower the oxygen cost of steady-state exercise or improve exercise performance in normoxia or hypoxia in a small sample of well-trained male cyclists. PMID:25811674

  11. Secondary hypoxia exacerbates acute disruptions of energy metabolism in rats resulting from fluid percussion injury.

    PubMed

    Bauman, Richard A; Widholm, John; Long, Joseph B

    2005-05-01

    The purpose of these experiments was to determine whether secondary hypoxia exacerbates the metabolic consequences of fluid percussion injury (FPI). In Experiment I, rats were trained to press a lever for their entire daily ration of food at any time during a 12-h light/dark cycle and run in an activity wheel. After food intake and body weight stabilized, rats were surgically prepared, assigned to one of four groups [FPI+Hypoxia (IH), FPI+Normoxia (IN), Sham Injury+Hypoxia (SH), Sham Injury+Normoxia (SN)] and, after recovery from surgery, anesthetized with halothane delivered by a 21% O2 source. Immediately after injury or sham injury, the O2 source was switched to 13% for rats in Groups IH and SH for 30 min. Post-traumatic hypoxemia exacerbated the ensuing FPI-induced reductions of food intake and body weight, but did not change FPI-induced reduction in wheel running. In Experiment II, rats were assigned to one of three groups (SH, IN, or IH) and subjected to sham injury and 13% O2 or FPI and either 13 or 21% O2. Immediately after 30 min of hypoxia or normoxia, rats were confined to metabolism cages that were used to quantify rates of oxygen consumption (VO2), carbon dioxide production (VCO2), and heat production (H). Post-traumatic hypoxia exacerbated the FPI-induced increases in VO2, VCO2, and H. The results of Experiments I and II provide convergent confirmation that secondary hypoxemia exacerbates the FPI-induced hypermetabolic state in rats and therefore might significantly exacerbate the brain injury-induced disruptions of energy metabolism in humans. PMID:15836897

  12. Severe physical exertion, oxidative stress, and acute lung injury.

    PubMed

    Shah, Nikunj R; Iqbal, M Bilal; Barlow, Andrew; Bayliss, John

    2011-11-01

    We report the case of a 27-year-old male athlete presenting with severe dyspnoea 24 hours after completing an "Ironman Triathlon." Subsequent chest radiology excluded pulmonary embolus but confirmed an acute lung injury (ALI). Echocardiography corroborated a normal brain natriuretic peptide level by demonstrating good biventricular systolic function with no regional wall motion abnormalities. He recovered well, without requiring ventilatory support, on supplemental oxygen therapy and empirical antibiotics. To date, ALI following severe physical exertion has never been described. Exercise is a form of physiological stress resulting in oxidative stress through generation of reactive oxygen/nitrogen species. In its extreme form, there is potential for an excessive oxidative stress response--one that overwhelms the body's protective antioxidant mechanisms. As our case demonstrated, oxidative stress secondary to severe physical exertion was the most likely factor in the pathogenesis of ALI. Further studies are necessary to explore the pathological consequences of exercise-induced oxidative stress. Although unproven as of yet, further research may be needed to demonstrate if antioxidant therapy can prevent or ameliorate potential life-threatening complications in the acute setting. PMID:22064719

  13. Transmission Dynamics and Control of Severe Acute Respiratory Syndrome

    NASA Astrophysics Data System (ADS)

    Lipsitch, Marc; Cohen, Ted; Cooper, Ben; Robins, James M.; Ma, Stefan; James, Lyn; Gopalakrishna, Gowri; Chew, Suok Kai; Tan, Chorh Chuan; Samore, Matthew H.; Fisman, David; Murray, Megan

    2003-06-01

    Severe acute respiratory syndrome (SARS) is a recently described illness of humans that has spread widely over the past 6 months. With the use of detailed epidemiologic data from Singapore and epidemic curves from other settings, we estimated the reproductive number for SARS in the absence of interventions and in the presence of control efforts. We estimate that a single infectious case of SARS will infect about three secondary cases in a population that has not yet instituted control measures. Public-health efforts to reduce transmission are expected to have a substantial impact on reducing the size of the epidemic.

  14. Exercise training normalizes renal blood flow responses to acute hypoxia in experimental heart failure: role of the α1-adrenergic receptor.

    PubMed

    Pügge, Carolin; Mediratta, Jai; Marcus, Noah J; Schultz, Harold D; Schiller, Alicia M; Zucker, Irving H

    2016-02-01

    Recent data suggest that exercise training (ExT) is beneficial in chronic heart failure (CHF) because it improves autonomic and peripheral vascular function. In this study, we hypothesized that ExT in the CHF state ameliorates the renal vasoconstrictor responses to hypoxia and that this beneficial effect is mediated by changes in α1-adrenergic receptor activation. CHF was induced in rabbits. Renal blood flow (RBF) and renal vascular conductance (RVC) responses to 6 min of 5% isocapnic hypoxia were assessed in the conscious state in sedentary (SED) and ExT rabbits with CHF with and without α1-adrenergic blockade. α1-adrenergic receptor expression in the kidney cortex was also evaluated. A significant decline in baseline RBF and RVC and an exaggerated renal vasoconstriction during acute hypoxia occurred in CHF-SED rabbits compared with the prepaced state (P < 0.05). ExT diminished the decline in baseline RBF and RVC and restored changes during hypoxia to those of the prepaced state. α1-adrenergic blockade partially prevented the decline in RBF and RVC in CHF-SED rabbits and eliminated the differences in hypoxia responses between SED and ExT animals. Unilateral renal denervation (DnX) blocked the hypoxia-induced renal vasoconstriction in CHF-SED rabbits. α1-adrenergic protein in the renal cortex of animals with CHF was increased in SED animals and normalized after ExT. These data provide evidence that the acute decline in RBF during hypoxia is caused entirely by the renal nerves but is only partially mediated by α1-adrenergic receptors. Nonetheless, α1-adrenergic receptors play an important role in the beneficial effects of ExT in the kidney. PMID:26607245

  15. Ca2+ responses of pulmonary arterial myocytes to acute hypoxia require release from ryanodine and inositol trisphosphate receptors in sarcoplasmic reticulum

    PubMed Central

    Wang, Jian; Shimoda, Larissa A.

    2012-01-01

    In pulmonary arterial smooth muscle cells (PASMC), acute hypoxia increases intracellular Ca2+ concentration ([Ca2+]i) by inducing Ca2+ release from the sarcoplasmic reticulum (SR) and Ca2+ influx through store- and voltage-operated Ca2+ channels in sarcolemma. To evaluate the mechanisms of hypoxic Ca2+ release, we measured [Ca2+]i with fluorescent microscopy in primary cultures of rat distal PASMC. In cells perfused with Ca2+-free Krebs Ringer bicarbonate solution (KRBS), brief exposures to caffeine (30 mM) and norepinephrine (300 μM), which activate SR ryanodine and inositol trisphosphate receptors (RyR, IP3R), respectively, or 4% O2 caused rapid transient increases in [Ca2+]i, indicating intracellular Ca2+ release. Preexposure of these cells to caffeine, norepinephrine, or the SR Ca2+-ATPase inhibitor cyclopiazonic acid (CPA; 10 μM) blocked subsequent Ca2+ release to caffeine, norepinephrine, and hypoxia. The RyR antagonist ryanodine (10 μM) blocked Ca2+ release to caffeine and hypoxia but not norepinephrine. The IP3R antagonist xestospongin C (XeC, 0.1 μM) blocked Ca2+ release to norepinephrine and hypoxia but not caffeine. In PASMC perfused with normal KRBS, acute hypoxia caused a sustained increase in [Ca2+]i that was abolished by ryanodine or XeC. These results suggest that in rat distal PASMC 1) the initial increase in [Ca2+]i induced by hypoxia, as well as the subsequent Ca2+ influx that sustained this increase, required release of Ca2+ from both RyR and IP3R, and 2) the SR Ca2+ stores accessed by RyR, IP3R, and hypoxia functioned as a common store, which was replenished by a CPA-inhibitable Ca2+-ATPase. PMID:22582116

  16. Temporal dynamics of lactate concentration in the human brain during acute inspiratory hypoxia

    PubMed Central

    Harris, Ashley D; Roberton, Victoria H; Huckle, Danielle L; Saxena, Neeraj; Evans, C John; Murphy, Kevin; Hall, Judith E; Bailey, Damian M; Mitsis, Georgios; Edden, Richard A E; Wise, Richard G

    2012-01-01

    Purpose To demonstrate the feasibility of measuring the temporal dynamics of cerebral lactate concentration and examine these dynamics in human subjects using MRS during hypoxia. Methods A respiratory protocol consisting of 10 min baseline normoxia, 20 min inspiratory hypoxia and ending with 10 min normoxic recovery was used, throughout which lactate-edited MRS was performed. This was repeated four times in three subjects. A separate session was performed to measure blood lactate. Impulse response functions using end-tidal oxygen and blood lactate as system inputs and cerebral lactate as the system output were examined to describe the dynamics of the cerebral lactate response to a hypoxic challenge. Results The average lactate increase was 20%±15% during the last half of the hypoxic challenge. Significant changes in cerebral lactate concentration were observed after 400s. The average relative increase in blood lactate was 188%±95%. The temporal dynamics of cerebral lactate concentration was reproducibly demonstrated with 200s time bins of MRS data (coefficient of variation 0.063±0.035 between time bins in normoxia). The across subject coefficient of variation was 0.333. Conclusions The methods for measuring the dynamics of the cerebral lactate response developed here would be useful to further investigate the brain’s response to hypoxia. PMID:23197421

  17. Flupirtine effectively prevents development of acute neonatal seizures in an animal model of global hypoxia.

    PubMed

    Sampath, Dayalan; Shmueli, Doron; White, Andrew M; Raol, Yogendra H

    2015-10-21

    Current first-line drugs for the treatment of neonatal seizures have limited efficacy and are associated with side effects. Uncontrolled seizures may exacerbate brain injury and contribute to later-life neurological disability. Therefore, it is critical to develop a treatment for neonatal seizures that is effective and safe. In early-life, when the γ-aminobutyric acid (GABA) inhibitory system is not fully developed, potassium channels play an important role in controlling excitability. An earlier study demonstrated that flupirtine, a KCNQ potassium channel opener, is more efficacious than diazepam and phenobarbital for the treatment of chemoconvulsant-induced neonatal seizures. In newborns, seizures are most commonly associated with hypoxic-ischemic encephalopathy (HIE). Thus, in the present study, we examined the efficacy of flupirtine to treat neonatal seizures in an animal model of global hypoxia. Our results showed that flupirtine dose dependently blocks the occurrence of behavioral seizures in pups during hypoxia. Additionally, flupirtine inhibits the development of hypoxia-induced clinical seizures and associated epileptiform discharges, as well as purely electrographic (subclinical) seizures. These results suggest that flupirtine is an effective anti-seizure drug, and that further studies should be conducted to determine the time window within which it's administration can effectively treat neonatal seizures. PMID:26365409

  18. Acute hypoxia activates store-operated Ca2+ entry and increases intracellular Ca2+ concentration in rat distal pulmonary venous smooth muscle cells

    PubMed Central

    Peng, Gongyong; Lu, Wenju; Zhong, Nanshan

    2013-01-01

    Rationale Exposure to acute hypoxia causes vasoconstriction in both pulmonary arteries (PA) and pulmonary veins (PV). The mechanisms on the arterial side have been studied extensively. However, bare attention has been paid to the venous side. Objectives To investigate if acute hypoxia caused the increase of intracellular Ca2+ concentration ([Ca2+]i), and Ca2+ influx through store-operated calcium channels (SOCC) in pulmonary venous smooth muscle cells (PVSMCs). Methods Fluorescent microscopy and fura-2 were used to measure effects of 4% O2 on [Ca2+]i and store-operated Ca2+ entry (SOCE) in isolated rat distal PVSMCs. Measurements and main results In PVSMCs perfused with Ca2+-free Krebs Ringer bicarbonate solution (KRBS) containing cyclopiazonic acid to deplete Ca2+ stores in the sarcoplasmic reticulum (SR) and nifedipine to prevent Ca2+ entry through L-type voltage-depended Ca2+ channels (VDCC), hypoxia markedly enhanced both the increase in [Ca2+]i caused by restoration of extracellular [Ca2+] and the rate at which extracellular Mn2+ quenched fura-2 fluorescence. Moreover, the increased [Ca2+]i in PVSMCs perfused with normal salt solution was completely blocked by SOCC antagonists SKF-96365 and NiCl2 at concentrations that SOCE >85% was inhibited but [Ca2+]i responses to 60 mM KCl were not altered. On the contrary, L-type VDCC antagonist nifedipine inhibited increase in [Ca2+]i to hypoxia by only 50% at concentrations that completely blocked responses to KCl. The increased [Ca2+]i caused by hypoxia was completely abolished by perfusion with Ca2+-free KRBS. Conclusions These results suggest that acute hypoxia enhances SOCE via activating SOCCs, leading to increased [Ca2+]i in distal PVSMCs. PMID:24255773

  19. Acute severe asthma: new approaches to assessment and treatment.

    PubMed

    Papiris, Spyros A; Manali, Effrosyni D; Kolilekas, Likurgos; Triantafillidou, Christina; Tsangaris, Iraklis

    2009-01-01

    The precise definition of a severe asthmatic exacerbation is an issue that presents difficulties. The term 'status asthmaticus' relates severity to outcome and has been used to define a severe asthmatic exacerbation that does not respond to and/or perilously delays the repetitive or continuous administration of short-acting inhaled beta(2)-adrenergic receptor agonists (SABA) in the emergency setting. However, a number of limitations exist concerning the quantification of unresponsiveness. Therefore, the term 'acute severe asthma' is widely used, relating severity mostly to a combination of the presenting signs and symptoms and the severity of the cardiorespiratory abnormalities observed, although it is well known that presentation does not foretell outcome. In an acute severe asthma episode, close observation plus aggressive administration of bronchodilators (SABAs plus ipratropium bromide via a nebulizer driven by oxygen) and oral or intravenous corticosteroids are necessary to arrest the progression to severe hypercapnic respiratory failure leading to a decrease in consciousness that requires intensive care unit (ICU) admission and, eventually, ventilatory support. Adjunctive therapies (intravenous magnesium sulfate and/or others) should be considered in order to avoid intubation. Management after admission to the hospital ward because of an incomplete response is similar. The decision to intubate is essentially based on clinical judgement. Although cardiac or respiratory arrest represents an absolute indication for intubation, the usual picture is that of a conscious patient struggling to breathe. Factors associated with the increased likelihood of intubation include exhaustion and fatigue despite maximal therapy, deteriorating mental status, refractory hypoxaemia, increasing hypercapnia, haemodynamic instability and impending coma or apnoea. To intubate, sedation is indicated in order to improve comfort, safety and patient-ventilator synchrony, while at the

  20. Mechanisms of Severe Acute Respiratory Syndrome Coronavirus-Induced Acute Lung Injury

    PubMed Central

    Gralinski, Lisa E.; Bankhead, Armand; Jeng, Sophia; Menachery, Vineet D.; Proll, Sean; Belisle, Sarah E.; Matzke, Melissa; Webb-Robertson, Bobbie-Jo M.; Luna, Maria L.; Shukla, Anil K.; Ferris, Martin T.; Bolles, Meagan; Chang, Jean; Aicher, Lauri; Waters, Katrina M.; Smith, Richard D.; Metz, Thomas O.; Law, G. Lynn; Katze, Michael G.; McWeeney, Shannon; Baric, Ralph S.

    2013-01-01

    ABSTRACT Systems biology offers considerable promise in uncovering novel pathways by which viruses and other microbial pathogens interact with host signaling and expression networks to mediate disease severity. In this study, we have developed an unbiased modeling approach to identify new pathways and network connections mediating acute lung injury, using severe acute respiratory syndrome coronavirus (SARS-CoV) as a model pathogen. We utilized a time course of matched virologic, pathological, and transcriptomic data within a novel methodological framework that can detect pathway enrichment among key highly connected network genes. This unbiased approach produced a high-priority list of 4 genes in one pathway out of over 3,500 genes that were differentially expressed following SARS-CoV infection. With these data, we predicted that the urokinase and other wound repair pathways would regulate lethal versus sublethal disease following SARS-CoV infection in mice. We validated the importance of the urokinase pathway for SARS-CoV disease severity using genetically defined knockout mice, proteomic correlates of pathway activation, and pathological disease severity. The results of these studies demonstrate that a fine balance exists between host coagulation and fibrinolysin pathways regulating pathological disease outcomes, including diffuse alveolar damage and acute lung injury, following infection with highly pathogenic respiratory viruses, such as SARS-CoV. PMID:23919993

  1. Accounts of severe acute obstetric complications in Rural Bangladesh

    PubMed Central

    2011-01-01

    Background As maternal deaths have decreased worldwide, increasing attention has been placed on the study of severe obstetric complications, such as hemorrhage, eclampsia, and obstructed labor, to identify where improvements can be made in maternal health. Though access to medical care is considered to be life-saving during obstetric emergencies, data on the factors associated with health care decision-making during obstetric emergencies are lacking. We aim to describe the health care decision-making process during severe acute obstetric complications among women and their families in rural Bangladesh. Methods Using the pregnancy surveillance infrastructure from a large community trial in northwest rural Bangladesh, we nested a qualitative study to document barriers to timely receipt of medical care for severe obstetric complications. We conducted 40 semi-structured, in-depth interviews with women reporting severe acute obstetric complications and purposively selected for conditions representing the top five most common obstetric complications. The interviews were transcribed and coded to highlight common themes and to develop an overall conceptual model. Results Women attributed their life-threatening experiences to societal and socioeconomic factors that led to delays in seeking timely medical care by decision makers, usually husbands or other male relatives. Despite the dominance of male relatives and husbands in the decision-making process, women who underwent induced abortions made their own decisions about their health care and relied on female relatives for advice. The study shows that non-certified providers such as village doctors and untrained birth attendants were the first-line providers for women in all categories of severe complications. Coordination of transportation and finances was often arranged through mobile phones, and referrals were likely to be provided by village doctors. Conclusions Strategies to increase timely and appropriate care seeking

  2. Severe Hypertriglyceridemia During Therapy For Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Bhojwani, Deepa; Darbandi, Rashid; Pei, Deqing; Ramsey, Laura B.; Chemaitilly, Wassim; Sandlund, John T.; Cheng, Cheng; Pui, Ching-Hon; Relling, Mary V.; Jeha, Sima; Metzger, Monika L.

    2014-01-01

    Background Asparaginase and steroids can cause hypertriglyceridemia in children with acute lymphoblastic leukemia (ALL). There are no guidelines for screening or management of patients with severe hypertriglyceridemia (>1000 mg/dL) during ALL therapy. Patients and Methods Fasting lipid profiles were obtained prospectively at 4 time-points for 257 children consecutively enrolled on a frontline ALL study. Risk factors were evaluated by the exact chi-square test. Details of adverse events and management of hypertriglyceridemia were extracted retrospectively. Results Eighteen of 257 (7%) patients developed severe hypertriglyceridemia. Older age and treatment with higher doses of asparaginase and steroids on the standard/high-risk arm were significant risk factors. Severe hypertriglyceridemia was not associated with pancreatitis after adjustment for age and treatment arm or with osteonecrosis after adjustment for age. However, patients with severe hypertriglyceridemia had a 2.5 to 3 times higher risk of thrombosis compared to patients without, albeit the difference was not statistical significant. Of the 30 episodes of severe hypertriglyceridemia in 18 patients, 7 were managed conservatively while the others with pharmacotherapy. Seventeen of 18 patients continued to receive asparaginase and steroids. Triglyceride levels normalized after completion of ALL therapy in all 12 patients with available measurements. Conclusion Asparaginase- and steroid-induced transient hypertriglyceridemia can be adequately managed with dietary modifications and close monitoring without altering chemotherapy. Patients with severe hypertriglyceridemia were not at increased risk of adverse events, with a possible exception of thrombosis. The benefit of pharmacotherapy in decreasing symptoms and potential complications requires further investigation. PMID:25087182

  3. Contemporary management of infected necrosis complicating severe acute pancreatitis

    PubMed Central

    Jamdar, Saurabh; Siriwardena, Ajith K

    2006-01-01

    Pancreatic necrosis complicating severe acute pancreatitis is a challenging scenario in contemporary critical care practice; it requires multidisciplinary care in a setting where there is a relatively limited evidence base to support decision making. This commentary provides a concise overview of current management of patients with infected necrosis, focusing on detection, the role of pharmacologic intervention, and the timing and nature of surgical interventions. Fine-needle aspiration of necrosis remains the mainstay for establishment of infection. Pharmacological intervention includes antibiotic therapy as an adjunct to surgical debridement/drainage and, more recently, drotrecogin alfa. Specific concerns remain regarding the suitability of drotrecogin alfa in this setting. Early surgical intervention is unhelpful; surgery is indicated when there is strong evidence for infection of necrotic tissue, with the current trend being toward 'less drastic' surgical interventions. PMID:16356213

  4. Acute Lipotoxicity Regulates Severity of Biliary Acute Pancreatitis without Affecting Its Initiation

    PubMed Central

    Durgampudi, Chandra; Noel, Pawan; Patel, Krutika; Cline, Rachel; Trivedi, Ram N.; DeLany, James P.; Yadav, Dhiraj; Papachristou, Georgios I.; Lee, Kenneth; Acharya, Chathur; Jaligama, Deepthi; Navina, Sarah; Murad, Faris; Singh, Vijay P.

    2015-01-01

    Obese patients have worse outcomes during acute pancreatitis (AP). Previous animal models of AP have found worse outcomes in obese rodents who may have a baseline proinflammatory state. Our aim was to study the role of acute lipolytic generation of fatty acids on local severity and systemic complications of AP. Human postpancreatitis necrotic collections were analyzed for unsaturated fatty acids (UFAs) and saturated fatty acids. A model of biliary AP was designed to replicate the human variables by intraductal injection of the triglyceride glyceryl trilinoleate alone or with the chemically distinct lipase inhibitors orlistat or cetilistat. Parameters of AP etiology and outcomes of local and systemic severity were measured. Patients with postpancreatitis necrotic collections were obese, and 13 of 15 had biliary AP. Postpancreatitis necrotic collections were enriched in UFAs. Intraductal glyceryl trilinoleate with or without the lipase inhibitors resulted in oil red O–positive areas, resembling intrapancreatic fat. Both lipase inhibitors reduced the glyceryl trilinoleate–induced increase in serum lipase, UFAs, pancreatic necrosis, serum inflammatory markers, systemic injury, and mortality but not serum alanine aminotransferase, bilirubin, or amylase. We conclude that UFAs are enriched in human necrotic collections and acute UFA generation via lipolysis worsens pancreatic necrosis, systemic inflammation, and injury associated with severe AP. Inhibition of lipolysis reduces UFA generation and improves these outcomes of AP without interfering with its induction. PMID:24854864

  5. Cerebral Hypoxia

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Cerebral Hypoxia Information Page Synonym(s): Hypoxia, Anoxia Table of Contents ( ... Trials Organizations Publicaciones en Español What is Cerebral Hypoxia? Cerebral hypoxia refers to a condition in which ...

  6. Dopamine treatment during acute hypoxia is neuroprotective in the developing sheep brain.

    PubMed

    Brew, N; Azhan, A; den Heijer, I; Boomgardt, M; Davies, G I; Nitsos, I; Miller, S L; Walker, A M; Walker, D W; Wong, F Y

    2016-03-01

    Dopamine is often used to treat hypotension in preterm infants; these infants are at risk of developing brain injury due to impaired autoregulation and cerebral hypoperfusion. However the effects of dopamine on the immature brain under conditions of cerebral hypoxia are not known. We hypothesized that pretreatment with dopamine would protect the immature brain from injury caused by cerebral hypoxia. Preterm fetal sheep were used to determine the effects of intravenous dopamine on hypoxia-induced brain injury. In 16 pregnant sheep at 90days of gestation (0.6 of term, term=147days) catheters were implanted aseptically into the fetal carotid artery and jugular vein; an inflatable occluder was placed loosely around the umbilical cord for later induction of fetal hypoxemia. At 5days after surgery, dopamine (10μg/kg/min, n=7 fetuses) or saline (n=9 fetuses) was infused for 74h. Two hours after commencing the dopamine/saline infusion, we induced umbilical cord occlusion (UCO) for up to 25min to produce fetal asphyxia. Fetuses were allowed to recover, and brains were collected 72h later for assessment of neuropathology. Un-operated twin fetuses were used as age-matched non-UCO controls (n=8). In UCO+saline fetuses, microglial and apoptotic cell density in the subcortical and periventricular white matter, caudate nucleus and hippocampus was greater than that in age-matched controls; oxidative stress was elevated in the subcortical and periventricular white matter and caudate nucleus compared to that in age-matched controls. In UCO+dopamine fetuses microglial density and oxidative stress in the cerebral white matter and caudate nucleus were not different to that of age-matched controls. Apoptotic cell death was decreased in the cerebral white matter of UCO+dopamine brains, relative to UCO+saline brains. We conclude that pretreatment with dopamine does not exacerbate hypoxia-induced injury in the immature brain and may be neuroprotective because it led to decreased apoptosis

  7. Cerebral perturbations during exercise in hypoxia.

    PubMed

    Verges, Samuel; Rupp, Thomas; Jubeau, Marc; Wuyam, Bernard; Esteve, François; Levy, Patrick; Perrey, Stéphane; Millet, Guillaume Y

    2012-04-15

    Reduction of aerobic exercise performance observed under hypoxic conditions is mainly attributed to altered muscle metabolism due to impaired O(2) delivery. It has been recently proposed that hypoxia-induced cerebral perturbations may also contribute to exercise performance limitation. A significant reduction in cerebral oxygenation during whole body exercise has been reported in hypoxia compared with normoxia, while changes in cerebral perfusion may depend on the brain region, the level of arterial oxygenation and hyperventilation induced alterations in arterial CO(2). With the use of transcranial magnetic stimulation, inconsistent changes in cortical excitability have been reported in hypoxia, whereas a greater impairment in maximal voluntary activation following a fatiguing exercise has been suggested when arterial O(2) content is reduced. Electromyographic recordings during exercise showed an accelerated rise in central motor drive in hypoxia, probably to compensate for greater muscle contractile fatigue. This accelerated development of muscle fatigue in moderate hypoxia may be responsible for increased inhibitory afferent signals to the central nervous system leading to impaired central drive. In severe hypoxia (arterial O(2) saturation <70-75%), cerebral hypoxia per se may become an important contributor to impaired performance and reduced motor drive during prolonged exercise. This review examines the effects of acute and chronic reduction in arterial O(2) (and CO(2)) on cerebral blood flow and cerebral oxygenation, neuronal function, and central drive to the muscles. Direct and indirect influences of arterial deoxygenation on central command are separated. Methodological concerns as well as future research avenues are also considered. PMID:22319046

  8. Effects of acute hypoxia on the oxygen uptake kinetics of older adults during cycling exercise.

    PubMed

    Zerbini, Livio; Brighenti, Alfredo; Pellegrini, Barbara; Bortolan, Lorenzo; Antonetti, Tommaso; Schena, Federico

    2012-08-01

    Pulmonary oxygen uptake, heart rate (HR), and deoxyhemoglobin (HHb) kinetics were studied in a group of older adults exercising in hypoxic conditions. Fourteen healthy older adults (aged 66 ± 6 years) performed 4 exercise sessions that consisted of (i) an incremental test to exhaustion on a cycloergometer while breathing normoxic room air (fractional inspired oxygen (FiO(2)) = 20.9% O(2)); (ii) an incremental test to exhaustion on a cycloergometer while breathing hypoxic room air (FiO(2) = 15% O(2)); (iii) 3 repeated square wave cycling exercises at moderate intensity while breathing normoxic room air; and (iv) 3 repeated square wave cycling exercises at moderate intensity while breathing hypoxic room air. During all exercise sessions, pulmonary gas exchange was measured breath-by-breath; HHb was determined on the vastus lateralis muscle by near-infrared spectroscopy; and HR was collected beat-by-beat. The pulomary oxygen uptake kinetics became slower in hypoxia (31 ± 9 s) than in normoxia (27 ± 7 s) because of an increased mismatching between O(2) delivery to O(2) utilization at the level of the muscle. The HR and HHb kinetics did not change between hypoxia and normoxia. PMID:22680339

  9. Rosiglitazone attenuates the severity of hyperlipidemic severe acute pancreatitis in rats

    PubMed Central

    NIYAZ, BATUR; ZHAO, KAI-LIANG; LIU, LI-MIN; CHEN, CHEN; DENG, WEN-HONG; ZUO, TENG; SHI, QIAO; WANG, WEI-XING

    2013-01-01

    Peroxisome proliferator-activated receptor-γ (PPAR-γ) ligand regulates adipocyte differentiation and insulin sensitivity, and exerts antihyperlipidemic and anti-inflammatory effects. However, the mechanisms by which PPAR-γ ligands affect hyperlipidemia with severe acute pancreatitis (SAP) have not been fully elucidated. The present study investigated the effects of rosiglitazone, a PPAR-γ ligand, on hyperlipidemia with SAP in a rat model. The hyperlipidemia was induced with a high-fat diet and SAP was induced by the administration of sodium taurocholate (TCA). The hyperlipidemia was shown to aggravate the severity of the sodium taurocholate-induced SAP. However, rosiglitazone demonstrated significant antihyperlipidemic and anti-inflammatory effects in the rats with high-lipid diet-induced hyperlipidemia and SAP. PMID:24137303

  10. Relaxin prevents the development of severe acute pancreatitis

    PubMed Central

    Cosen-Binker, Laura Iris; Binker, Marcelo Gustavo; Cosen, Rodica; Negri, Gustavo; Tiscornia, Osvaldo

    2006-01-01

    AIM: To investigate the severity of acute pancreatitis (AP) is associated to the intensity of leukocyte activation, inflammatory up-regulation and microcirculatory disruption associated to ischemia-reperfusion injury. Microvascular integrity and inhibition of pro-inflammatory mediators are key-factors in the evolution of AP. Relaxin is an insulin-like hormone that has been attributed vasorelaxant properties via the nitric oxide pathway while behaving as a glucocorticoid receptor agonist. METHODS: AP was induced by the bilio-pancreatic duct-outlet-exclusion closed-duodenal-loops model. Treatment with relaxin was done at different time-points. Nitric oxide synthase inhibition by L-NAME and glucocorticoid receptor (GR) blockage by mifepristone was considered. AP severity was assessed by biochemical and histopathological analyses. RESULTS: Treatment with relaxin reduced serum amylase, lipase, C-reactive protein, IL-6, IL-10, hsp72, LDH and 8-isoprostane as well as pancreatic and lung myeloperoxidase. Acinar and fat necrosis, hemorrhage and neutrophil infiltrate were also decreased. ATP depletion and ADP/ATP ratio were reduced while caspases 2-3-8 and 9 activities were increased. L-NAME and mifepristone decreased the efficiency of relaxin. CONCLUSION: Relaxin resulted beneficial in the treatment of AP combining the properties of a GR agonist while preserving the microcirculation and favoring apoptosis over necrosis. PMID:16570348

  11. Treatment of severe acute pancreatitis and its complications.

    PubMed

    Zerem, Enver

    2014-10-14

    Severe acute pancreatitis (SAP), which is the most serious type of this disorder, is associated with high morbidity and mortality. SAP runs a biphasic course. During the first 1-2 wk, a pro-inflammatory response results in systemic inflammatory response syndrome (SIRS). If the SIRS is severe, it can lead to early multisystem organ failure (MOF). After the first 1-2 wk, a transition from a pro-inflammatory response to an anti-inflammatory response occurs; during this transition, the patient is at risk for intestinal flora translocation and the development of secondary infection of the necrotic tissue, which can result in sepsis and late MOF. Many recommendations have been made regarding SAP management and its complications. However, despite the reduction in overall mortality in the last decade, SAP is still associated with high mortality. In the majority of cases, sterile necrosis should be managed conservatively, whereas in infected necrotizing pancreatitis, the infected non-vital solid tissue should be removed to control the sepsis. Intervention should be delayed for as long as possible to allow better demarcation and liquefaction of the necrosis. Currently, the step-up approach (delay, drain, and debride) may be considered as the reference standard intervention for this disorder. PMID:25320523

  12. Supra- and Sub-Baseline Phosphocreatine Recovery in Developing Brain after Transient Hypoxia-Ischaemia: Relation to Baseline Energetics, Insult Severity and Outcome

    ERIC Educational Resources Information Center

    Iwata, Osuke; Iwata, Sachiko; Bainbridge, Alan; De Vita, Enrico; Matsuishi, Toyojiro; Cady, Ernest B.; Robertson, Nicola J.

    2008-01-01

    Following hypoxia-ischaemia (HI), an early biomarker of insult severity is desirable to target neuroprotective therapies to patients most likely to benefit; currently there are no biomarkers within the "latent phase" period before the establishment of secondary energy failure. Brief transient phosphocreatine (PCr) recovery overshoot (measured…

  13. Metronomic vinorelbine: Anti-angiogenic activity in vitro in normoxic and severe hypoxic conditions, and severe hypoxia-induced resistance to its anti-proliferative effect with reversal by Akt inhibition.

    PubMed

    Mavroeidis, L; Sheldon, H; Briasoulis, E; Marselos, M; Pappas, P; Harris, A L

    2015-08-01

    Metronomic chemotherapy is the protracted, dense administration of low sub-toxic doses of chemotherapy, to inhibit tumor angiogenesis. Vinorelbine is an orally bioavailable vinca alkaloid shown to be useable for metronomic administration. In clinical trials, metronomic vinorelbine has been demonstrated to generate sustainable antitumor efficacy at low nanomolar (nM) concentrations with negligible toxicity. We sought to determine whether the clinically relevant metronomic concentration of vinorelbine is anti-angiogenic in vitro and whether hypoxia, often induced by anti-angiogenic therapy, modifies its effectiveness. We found that the metronomic concentration of 10 nM vinorelbine inhibited human umbilical vein endothelial cell (HUVEC) proliferation, migration, tube formation and sprouting. Severe hypoxia, did not affect the inhibitory effect of metronomic vinorelbine on migration, tube formation and sprouting. However, severe hypoxia reduced its anti-proliferative effect by decreasing its ability to induce G2/M block as it shifted the cell population to the G1 phase and decreased the fraction of the cells in the DNA synthesis S phase. Furthermore, the pro-apoptotic effects of 10 nM vinorelbine were also decreased. Metronomic vinorelbine decreased the Bcl-2/Bax ratio in normoxia whereas the ratio was reduced in severe hypoxia but unaltered by vinorelbine treatment. Akt signals to an anti-apoptotic pathway and we demonstrated that the Akt inhibitor V reversed the protective effect of severe hypoxia. Thus, we provide evidence for the anti-angiogenic basis of metronomic vinorelbine and we show that severe hypoxia mediates resistance to its anti-proliferative effect on endothelial cells. Akt warrants further investigation as a potential target to circumvent this hypoxic resistance. PMID:26095084

  14. Effects of exercise in normoxia and acute hypoxia on respiratory muscle metabolites.

    PubMed

    Fregosi, R F; Dempsey, J A

    1986-04-01

    We determined changes in rat plantaris, diaphragm, and intercostal muscle metabolites following exercise of various intensities and durations, in normoxia and hypoxia (FIO2 = 0.12). Marked alveolar hyperventilation occurred during all exercise conditions, suggesting that respiratory muscle motor activity was high. [ATP] was maintained at rest levels in all muscles during all normoxic and hypoxic exercise bouts, but at the expense of creatine phosphate (CP) in plantaris muscle and diaphragm muscle following brief exercise at maximum O2 uptake (VO2max) in normoxia. In normoxic exercise plantaris [glycogen] fell as exercise exceeded 60% VO2max, and was reduced to less than 50% control during exhaustive endurance exercise (68% VO2max for 54 min and 84% for 38 min). Respiratory muscle [glycogen] was unchanged at VO2max as well as during either type of endurance exercise. Glucose 6-phosphate (G6P) rose consistently during heavy exercise in diaphragm but not in plantaris. With all types of exercise greater than 84% VO2max, lactate concentration ([LA]) in all three muscles rose to the same extent as arterial [LA], except at VO2max, where respiratory muscle [LA] rose to less than half that in arterial blood or plantaris. Exhaustive exercise in hypoxia caused marked hyperventilation and reduced arterial O2 content; glycogen fell in plantaris (20% of control) and in diaphragm (58%) and intercostals (44%). We conclude that respiratory muscle glycogen stores are spared during exhaustive exercise in the face of substantial glycogen utilization in plantaris, even under conditions of extreme hyperventilation and reduced O2 transport. This sparing effect is due primarily to G6P inhibition of glycogen phosphorylase in diaphragm muscle. The presence of elevated [LA] in the absence of glycogen utilization suggests that increased lactate uptake, rather than lactate production, occurred in the respiratory muscles during exhaustive exercise. PMID:3700306

  15. Severe Acute Axonal Neuropathy following Treatment with Arsenic Trioxide for Acute Promyelocytic Leukemia: a Case Report

    PubMed Central

    Kühn, Marcus; Sammartin, Kety; Nabergoj, Mitja; Vianello, Fabrizio

    2016-01-01

    Peripheral neuropathy is a common complication of arsenic toxicity. Symptoms are usually mild and reversible following discontinuation of treatment. A more severe chronic sensorimotor polyneuropathy characterized by distal axonal-loss neuropathy can be seen in chronic arsenic exposure. The clinical course of arsenic neurotoxicity in patients with coexistence of thiamine deficiency is only anecdotally known but this association may potentially lead to severe consequences. We describe a case of acute irreversible axonal neuropathy in a patient with hidden thiamine deficiency who was treated with a short course of arsenic trioxide for acute promyelocytic leukemia. Thiamine replacement therapy and arsenic trioxide discontinuation were not followed by neurological recovery and severe polyneuropathy persisted at 12-month follow-up. Thiamine plasma levels should be measured in patients who are candidate to arsenic trioxide therapy. Prophylactic administration of vitamin B1 may be advisable. The appearance of polyneuropathy signs early during the administration of arsenic trioxide should prompt electrodiagnostic testing to rule out a pattern of axonal neuropathy which would need immediate discontinuation of arsenic trioxide. PMID:27158436

  16. Chronic hypoxia alters mitochondrial composition in human macrophages.

    PubMed

    Fuhrmann, Dominik Christian; Wittig, Ilka; Heide, Heinrich; Dehne, Nathalie; Brüne, Bernhard

    2013-12-01

    Hypoxia inducible factors (HIFs) are important mediators of the cellular adaptive response during acute hypoxia. The role of HIF-1 and HIF-2 during prolonged periods of hypoxia, i.e. chronic hypoxia is less defined. Therefore, we used human THP-1 macrophages with a knockdown of either HIF-1α, HIF-2α, or both HIFα-subunits, incubated them for several days under hypoxia (1% O2), and analyzed responses to hypoxia using 2D-DIGE coupled to MS/MS-analysis. Chronic hypoxia was defined as a time point when the early but transient accumulation of HIFα-subunits and mRNA expression of classical HIF target genes returned towards basal levels, with a new steady state that was constant from 72h onwards. From roughly 800 spots, that were regulated comparing normoxia to chronic hypoxia, about 100 proteins were unambiguously assigned during MS/MS-analysis. Interestingly, a number of glycolytic proteins were up-regulated, while a number of inner mitochondrial membrane proteins were down-regulated independently of HIF-1α or HIF-2α. Chronic hypoxic conditions depleted the mitochondrial mass by autophagy, which occurred independently of HIF proteins. Macrophages tolerate periods of chronic hypoxia very well and adaptive responses occur, at least in part, independently of HIF-1α and/or HIF-2α and comprise mitophagy as a pathway of particular importance. PMID:24140568

  17. Epidemiology of severe acute respiratory syndrome (SARS): adults and children.

    PubMed

    Zhong, Nan-Shan; Wong, Gary W K

    2004-12-01

    Severe acute respiratory syndrome (SARS) is a newly described respiratory infection with pandemic potential. The causative agent is a new strain of coronavirus most likely originating from wild animals. This disease first emerged in November 2002 in Guangdong Province, China. Early in the outbreak the infection had been transmitted primarily via household contacts and healthcare settings. In late February 2003 the infection was transmitted to Hong Kong when an infected doctor from the mainland visited there. During his stay in Hong Kong at least 17 guests and visitors were infected at the hotel at which he stayed. By modern day air travel, the infection was rapidly spread to other countries including Vietnam, Singapore and Canada by these infected guests. With the implementation of effective control strategies including early isolation of suspected cases, strict infection control measures in the hospital setting, meticulous contact tracing and quarantine, the outbreak was finally brought under control by July 2003. In addition, there were another two events of SARS in China between the end of December 2003 and January 2004 and from March to May 2004; both were readily controlled without significant patient spread. PMID:15531250

  18. Intravenous glutamine for severe acute pancreatitis: A meta-analysis

    PubMed Central

    Zhong, Xin; Liang, Cui-Ping; Gong, Shu

    2013-01-01

    AIM: To evaluate the efficacy of intravenous glutamine on the patients with severe acute pancreatitis (SAP). METHODS: The Cochrane Library, PubMed, EMBASE, and EBM review databases were searched up to June 2012. Randomized controlled trials (RCTs) that compared non-glutamine nutrition with intravenous glutamine supplemented nutrition in patients with SAP were included. A method recommended by the Cochrane Collaboration was used to perform a meta-analysis of those RCTs. RESULTS: Four RCTs involving a total of 190 participants were included. Analysis of these RCTs revealed the presence of statistical homogeneity among them. Results showed that glutamine dipeptide has a positive effect in reducing the mortality rate (OR = 0.26, 95%CI: 0.09-0.73, P = 0.01), length of hospital stay (weighted mean difference = -4.85, 95%CI: 6.67--3.03, P < 0.001), and the rate of complications (OR = 0.41, 95%CI: 0.22-0.78, P = 0.006). No serious adverse effects were found. CONCLUSION: Current best evidence demonstrates that glutamine is effective for SAP. Further high quality trials are required and parameters of nutritional condition and hospital cost should be considered in future RCTs with sufficient size and rigorous design. PMID:24701410

  19. Early Nasogastric Feeding in Predicted Severe Acute Pancreatitis

    PubMed Central

    Eckerwall, Gunilla E.; Axelsson, Jakob B.; Andersson, Roland G.

    2006-01-01

    Objective: To compare the efficacy and safety of early, nasogastric enteral nutrition (EN) with total parenteral nutrition (TPN) in patients with predicted severe acute pancreatitis (SAP). Summary Background Data: In SAP, the magnitude of the inflammatory response as well as increased intestinal permeability correlates with outcome. Enteral feeding has been suggested superior to parenteral feeding due to a proposed beneficial effect on the gut barrier. Methods: Fifty patients who met the inclusion criteria were randomized to TPN or EN groups. The nutritional regimen was started within 24 hours from admission and EN was provided through a nasogastric tube. The observation period was 10 days. Intestinal permeability was measured by excretion of polyethylene glycol (PEG) and concentrations of antiendotoxin core antibodies (Endocab). Interleukins (IL)-6 IL-8, and C-reactive protein (CRP) were used as markers of the systemic inflammatory response. Morbidity and feasibility of the nutritional route were evaluated by the frequency of complications, gastrointestinal symptoms, and abdominal pain. Results: PEG, Endocab, CRP, IL-6, APACHE II score, severity according to the Atlanta classification (22 patients), and gastrointestinal symptoms or abdominal pain did not significantly differ between the groups. The incidence of hyperglycemia was significantly higher in TPN patients (21 of 26 vs. 7 of 23; P < 0.001). Total complications (25 vs. 52; P = 0.04) and pulmonary complications (10 vs. 21; P = 0.04) were significantly more frequent in EN patients, although complications were diagnosed dominantly within the first 3 days. Conclusion: In predicted SAP, nasogastric early EN was feasible and resulted in better control of blood glucose levels, although the overall early complication rate was higher in the EN group. No beneficial effects on intestinal permeability or the inflammatory response were seen by EN treatment. PMID:17122621

  20. The severe acute respiratory syndrome epidemic in mainland China dissected

    PubMed Central

    Cao, Wu-Chun; de Vlas, Sake J.; Richardus, Jan Hendrik

    2011-01-01

    This paper provides a review of a recently published series of studies that give a detailed and comprehensive documentation of the severe acute respiratory syndrome (SARS) epidemic in mainland China, which severely struck the country in the spring of 2003. The epidemic spanned a large geographical extent but clustered in two areas: first in Guangdong Province, and about 3 months later in Beijing with its surrounding areas. Reanalysis of all available epidemiological data resulted in a total of 5327 probable cases of SARS, of whom 343 died. The resulting case fatality ratio (CFR) of 6.4% was less than half of that in other SARS-affected countries or areas, and this difference could only partly be explained by younger age of patients and higher number of community acquired infections. Analysis of the impact of interventions demonstrated that strong political commitment and a centrally coordinated response was the most important factor to control SARS in mainland China, whereas the most stringent control measures were all initiated when the epidemic was already dying down. The long-term economic consequence of the epidemic was limited, much consumption was merely postponed, but for Beijing irrecoverable losses to the tourist sector were considerable. An important finding from a cohort study was that many former SARS patients currently suffer from avascular osteonecrosis, as a consequence of the treatment with corticosteroids during their infection. The SARS epidemic provided valuable information and lessons relevant in controlling outbreaks of newly emerging infectious diseases, and has led to fundamental reforms of the Chinese health system. In particular, a comprehensive nationwide internet-based disease reporting system was established. PMID:24470901

  1. Regulation of cardiac output in hypoxia.

    PubMed

    Siebenmann, Christoph; Lundby, Carsten

    2015-12-01

    This brief review addresses the regulation of cardiac output (Q) at rest and during submaximal exercise in acute and chronic hypoxia. To preserve systemic O2 delivery in acute hypoxia Q is increased by an acceleration of heart rate, whereas stroke volume (SV) remains unchanged. Tachycardia is governed by activation of carotid and aortic chemoreceptors and a concomitant reduction in arterial baroreflex activation, all balancing sympathovagal activity toward sympathetic dominance. As hypoxia extends over several days a combination of different adaptive processes restores arterial O2 content to or beyond sea level values and hence Q normalizes. The latter however occurs as a consequence of a decrease in SV whereas tachycardia persists. The diminished SV reflects a lower left ventricular end-diastolic volume which is primarily related to hypoxia-generated reduction in plasma volume. Hypoxic pulmonary vasoconstriction may contribute by increasing right ventricular afterload and thus decreasing its ejection fraction. In summary, the Q response to hypoxia is the result of a complex interplay between several physiological mechanisms. Future studies are encouraged to establish the individual contributions of the different components from an integrative perspective. PMID:26589118

  2. Respiratory autoresuscitation following severe acute hypoxemia in anesthetized adult rats.

    PubMed

    Krause, A; Nowak, Z; Srbu, R; Bell, H J

    2016-10-01

    In the present study we investigated the pattern and efficacy of respiratory autoresuscitation in spontaneously breathing adult male rats across three separate anesthetic backgrounds. Each animal was administered one of three injectable anesthetics to achieve a surgical plane of anesthesia: ketamine-xylazine (KET, n=10), pentobarbital (PEN, n=10), or urethane (URE, n=10). Animals were tracheostomized and equipped with a femoral artery catheter to record airflow and arterial pressures. In response to a bout of breathing anoxic air, none of the 10 URE animals were able to mount a successful autoresuscitation response. In contrast, all KET and PEN animals survived all four consecutive anoxic exposures, restoring eupneic breathing in all cases. Moreover, only 4/10 URE animals expressed gasping breaths following the onset of respiratory arrest, and these were temporally delayed (p<0.001) and much smaller in volume (P≤0.012) compared to KET and PEN animals. URE animals showed no clear aberrations in their cardiovascular responses to anoxia, with the exception of lower arterial pulse pressures compared to either KET or PEN animals at specific points following RA. Ketamine-xylazine and pentobarbital anesthesia can be reliably and effectively used to create models for the study of autoresuscitation in adult rats. In contrast, urethane causes catastrophic failure of respiratory autoresuscitation, by delaying or outright preventing the elaboration of gasping breaths following anoxia-induced respiratory arrest. The neuronal and synaptic alterations accompanying urethane anesthesia may therefore provide a means of understanding potential pathological alterations in rhythm generation that can predispose the respiratory control system to failed autoresuscitation following an episode of acute severe hypoxemia. PMID:27378495

  3. Effects of acute hypoxia on cardiopulmonary responses to head-down tilt

    NASA Technical Reports Server (NTRS)

    Loeppky, J. A.; Luft, U. C.; Scotto, P.; Chick, T. W.

    1990-01-01

    Six male subjects were exposed on two separate occasions to simulated microgravity with 28 deg head-down tilt (HD) for 1 h with baseline followed by recovery at + 17 deg head-up. Pulmonary ventilation, gas exchange, spirometry, and central and cerebral blood flow characteristics were compared while breathing ambient air and reduced F(I)O2 equivalent to 14,828 ft. With hypoxia (HY), the increased tidal volume served to attenuate the drop in arterial saturation by reducing deadspace ventilation. Arterial and mixed venous PO2, values, estimated from peripheral venous samples and cardiac output (CO), were both maintained during HD in HY. Mixed venous PO2 was elevated by an increase in CO associated with a reduction in systemic resistance. Changes in spirometric indices during HD were not accentuated by HY, making the presence of interstitial edema unlikely. Cerebral flow and resistance showed minor reductions with HD. Tissue oxygenation and cardiopulmonary function were not notably effected by HD during HY, but a combination of these two stressors may predispose subjects to subsequent orthostatic intolerance during initial recovery.

  4. Reserved higher vagal tone under acute hypoxia in Tibetan adolescents with long-term migration to sea level.

    PubMed

    Zhuang, Jianguo; Zhu, Haifeng; Zhou, Zhaonian

    2002-02-01

    Tibetans are known as one of the largest and oldest high-altitude natives in the world and are among the best high-altitude-adapted ethnic groups. They exhibit greater vagal tone and less sympathetic stimulation than acclimatized lowlanders at high altitudes. Whether young native Tibetans who had spent long-term residence (more than 3 years) at sea level still reserved their unique autonomic characteristics was the main aim of this study. Heart rate variability (HRV) of 10 native young Tibetan male students and 12 Han counterparts were measured at resting supine position at sea level and 1 h after ascent to 3,700 m in a hypobaric chamber (PO(2) = 13.4 kPa). At sea level, Tibetans showed lower heart rate (HR) and greater HRV. At 3,700 m, the increase of HR was greater in the Hans than in the Tibetans, and the HRV was significantly diminished in the Han group but not in the Tibetan group. The results suggested that Tibetans had a greater parasympathetic dominance over the heart at rest, and acute moderate (3,700 m) hypoxia did not influence their HRV significantly, but it did on the Han subjects. We concluded that the long-term residence of the Tibetans at sea level did not change their unique characteristics of the autonomic systems. PMID:12047802

  5. Efficacy of Acute Intermittent Hypoxia on Physical Function and Health Status in Humans with Spinal Cord Injury: A Brief Review

    PubMed Central

    Astorino, Todd A.; Harness, Eric T.; White, Ailish C.

    2015-01-01

    Spinal cord injury (SCI) results in a loss of motor and sensory function and is consequent with reductions in locomotion, leading to a relatively sedentary lifestyle which predisposes individuals to premature morbidity and mortality. Many exercise modalities have been employed to improve physical function and health status in SCI, yet they are typically expensive, require many trained clinicians to implement, and are thus relegated to specialized rehabilitation centers. These characteristics of traditional exercise-based rehabilitation in SCI make their application relatively impractical considering the time-intensive nature of these regimens and patients' poor access to exercise. A promising approach to improve physical function in persons with SCI is exposure to acute intermittent hypoxia (IH) in the form of a small amount of sessions of brief, repeated exposures to low oxygen gas mixtures interspersed with normoxic breathing. This review summarizes the clinical application of IH in humans with SCI, describes recommended dosing and potential side effects of IH, and reviews existing data concerning the efficacy of relatively brief exposures of IH to modify health and physical function. Potential mechanisms explaining the effects of IH are also discussed. Collectively, IH appears to be a safe, time-efficient, and robust approach to enhance physical function in chronic, incomplete SCI. PMID:26167303

  6. Levels of interleukin-6, superoxide dismutase and malondialdehyde in the lung tissue of a rat model of hypoxia-induced acute pulmonary edema

    PubMed Central

    GAO, HENGBO; TIAN, YINGPING; WANG, WEI; YAO, DONGQI; ZHENG, TUOKANG; MENG, QINGBING

    2016-01-01

    The present study aimed to investigate the levels of malondialdehyde (MDA), superoxide dismutase (SOD) and interleukin (IL)-6 in the lung tissue of a rat model of acute pulmonary edema induced by acute hypoxia, and its pathophysiological significance. A total of 48 adult Wistar rats were randomly divided into group A, a normal group; group B, a model of acute pulmonary edema induced by hypoxia for 24 h; group C, a model of acute pulmonary edema induced by hypoxia for 48 h; and group D, a model of acute pulmonary edema induced by hypoxia for 72 h. The rats in groups B-D were intraperitoneally injected with 6% ammonium chloride to establish the model of acute pulmonary edema, and were subsequently sacrificed following successful modeling for 24, 48 and 72 h. The plasma of rats was isolated and the lungs of the rats were removed. Subsequently, a 10% lung homogenate was prepared and the contents and the activities of MDA, SOD and IL-6 in the lung tissue and IL-6 in the plasma were detected by enzyme-linked immunosorbent assay. MDA and IL-6 expression levels increased and SOD activity decreased in the lung tissue in group B as compared with group A; however the difference did not reach significance (P>0.05). MDA, IL-6 and SOD levels in the lung tissue of rats were significantly altered following the increased duration of pulmonary edema in groups C and D, as compared group A (P<0.05). The plasma IL-6 levels of the rats in groups B-D significantly increased, as compared with those in group A (P<0.05). In conclusion, the results of the present study demonstrated that the incidence of acute pulmonary edema may be associated with oxidative stress. Furthermore, decreased antioxidant capacity and increased free radical levels may be associated with pulmonary edema, as in the present study the levels of IL-6, SOD and MDA in the lung tissue were observed to be associated with the pathological changes of the disease. PMID:26998026

  7. Hydrogen Peroxide Accumulation in the Choroid During Intermittent Hypoxia Increases Risk of Severe Oxygen-Induced Retinopathy in Neonatal Rats

    PubMed Central

    Beharry, Kay D.; Cai, Charles L.; Sharma, Poonam; Bronshtein, Vadim; Valencia, Gloria B.; Lazzaro, Douglas R.; Aranda, Jacob V.

    2013-01-01

    Purpose. Extremely low gestational age neonates (ELGANs) requiring oxygen therapy often experience frequent episodes of intermittent hypoxia (IH) and are at high risk for severe retinopathy of prematurity (ROP). Using an established model for oxygen-induced retinopathy (OIR), we examined the hypothesis that there is a critical number of daily brief IH episodes which will result in irreversible retinal oxidative damage. Methods. Newborn rats were exposed to increasing daily clustered IH episodes (12% O2 with 50% O2) from postnatal day (P) 0 to P7 or P0 to P14, or placed in room air (RA) until P21 following 7- or 14-day IH. RA littermates at P7, P14, and P21 served as controls. A group exposed to constant 50% O2 (CH) served as a second control. Blood gases, eye opening at P14, retinal, and choroidal oxidative stress and lipid peroxidation (8-isoPGF2α), oxidants (H2O2) and antioxidants (catalase and SOD), retinal pathology (adenosine diphosphatase (ADPase)-stained retinal flatmounts), and mitochondria-related genes were assessed. Results. pO2 levels were higher with increasing IH episodes and remained elevated during the reoxygenation period. High SO2 levels were associated with most severe OIR. Levels of all measured biomarkers peaked with six IH episodes and decreased with 8 to 12 episodes. H2O2 accumulated in the choroid during the reoxygenation period with irreversible retinal damage. Conclusions. Our data suggest that six is the maximum number of IH episodes that the retina can sustain. Accumulation of H2O2 in the choroid may result in high levels being delivered to the entire retina, ultimately resulting in irreversible retinal oxidative damage. PMID:24168990

  8. Physiological noise in murine solid tumours using T2*-weighted gradient-echo imaging: a marker of tumour acute hypoxia?

    NASA Astrophysics Data System (ADS)

    Baudelet, Christine; Ansiaux, Réginald; Jordan, Bénédicte F.; Havaux, Xavier; Macq, Benoit; Gallez, Bernard

    2004-08-01

    with no contrast enhancement as the result of vessel functional impairment. Furthermore, transient fluctuations appeared to occur preferentially in neoangiogenic hyperpermeable vessels. The present study suggests that spontaneous T2*-weighted GRE fluctuations are very likely to be related to the spontaneous fluctuations in blood flow and oxygenation associated with the pathophysiology of acute hypoxia in tumours. The disadvantage of the T2*-weighted GRE MRI technique is the complexity of signal interpretation with regard to pO2 changes. Compared to established techniques such as intravital microscopy or histological assessments, the major advantage of the MRI technique lies in its capacity to provide simultaneously both temporal and detailed spatial information on spontaneous fluctuations throughout the tumour.

  9. Impaired Bile Acid Homeostasis in Children with Severe Acute Malnutrition

    PubMed Central

    Zhang, Ling; Voskuijl, Wieger; Mouzaki, Marialena; Groen, Albert K.; Alexander, Jennifer; Bourdon, Celine; Wang, Alice; Versloot, Christian J.; Di Giovanni, Valeria; Wanders, Ronald J. A.; Bandsma, Robert

    2016-01-01

    Objective Severe acute malnutrition (SAM) is a major cause of mortality in children under 5 years and is associated with hepatic steatosis. Bile acids are synthesized in the liver and participate in dietary fat digestion, regulation of energy expenditure, and immune responses. The aim of this work was to investigate whether SAM is associated with clinically relevant changes in bile acid homeostasis. Design An initial discovery cohort with 5 healthy controls and 22 SAM-patients was used to identify altered bile acid homeostasis. A follow up cohort of 40 SAM-patients were then studied on admission and 3 days after clinical stabilization to assess recovery in bile acid metabolism. Recruited children were 6–60 months old and admitted for SAM in Malawi. Clinical characteristics, feces and blood were collected on admission and prior to discharge. Bile acids, 7α-hydroxy-4-cholesten-3-one (C4) and FGF-19 were quantified. Results On admission, total serum bile acids were higher in children with SAM than in healthy controls and glycine-conjugates accounted for most of this accumulation with median and interquartile range (IQR) of 24.6 μmol/L [8.6–47.7] compared to 1.9 μmol/L [1.7–3.3] (p = 0.01) in controls. Total serum bile acid concentrations did not decrease prior to discharge. On admission, fecal conjugated bile acids were lower and secondary bile acids higher at admission compared to pre- discharge, suggesting increased bacterial conversion. FGF19 (Fibroblast growth factor 19), a marker of intestinal bile acid signaling, was higher on admission and was associated with decreased C4 concentrations as a marker of bile acid synthesis. Upon recovery, fecal calprotectin, a marker of intestinal inflammation, was lower. Conclusion SAM is associated with increased serum bile acid levels despite reduced synthesis rates. In SAM, there tends to be increased deconjugation of bile acids and conversion from primary to secondary bile acids, which may contribute to the

  10. Severe acute respiratory syndrome: clinical and laboratory manifestations.

    PubMed

    Lam, Christopher W K; Chan, Michael H M; Wong, Chun K

    2004-05-01

    Severe acute respiratory syndrome (SARS) is a recently emerged infectious disease with significant morbidity and mortality. An epidemic in 2003 affected 8,098 patients in 29 countries with 774 deaths. The aetiological agent is a new coronavirus spread by droplet transmission. Clinical and general laboratory manifestations included fever, chills, rigor, myalgia, malaise, diarrhoea, cough, dyspnoea, pneumonia, lymphopenia, neutrophilia, thrombocytopenia, and elevated serum lactate dehydrogenase (LD), alanine aminotransferase (ALT) and creatine kinase (CK) activities. Treatment has been empirical; initial potent antibiotic cover, followed by simultaneous ribavirin and corticosteroids, with or without pulse high-dose methylprednisolone, have been used. The postulated disease progression comprises (1) active viral infection, (2) hyperactive immune response, and (3) recovery or pulmonary destruction and death. We investigated serum LD isoenzymes and blood lymphocyte subsets of SARS patients, and found LD1 activity as the best biochemical prognostic indicator for death, while CD3+, CD4+, CD8+ and natural killer cell counts were promising predictors for intensive care unit (ICU) admission. Plasma cytokine and chemokine profiles showed markedly elevated Th1 cytokine interferon (IFN)-gamma, inflammatory cytokines interleukin (IL)-1beta, IL-6 and IL-12, neutrophil chemokine IL-8, monocyte chemoattractant protein-1 (MCP-1), and Th1 chemokine IFN-gamma-inducible protein-10 (IP-10) for at least two weeks after disease onset, but there was no significant elevation of inflammatory cytokine tumor necrosis factor (TNF)-alpha and anti-inflammatory cytokine IL-10. Corticosteroid reduced IL-8, MCP-1 and IP-10 concentrations from 5-8 days after treatment. Measurement of biochemical markers of bone metabolism demonstrated significant but transient increase in bone resorption from Day 28-44 after onset of fever, when pulse steroid was most frequently given. With tapering down of steroid

  11. Early Treatment of Severe Acute Respiratory Distress Syndrome.

    PubMed

    Przybysz, Thomas M; Heffner, Alan C

    2016-02-01

    Acute respiratory distress syndrome (ARDS) is defined by acute diffuse inflammatory lung injury invoked by a variety of systemic or pulmonary insults. Despite medical progress in management, mortality remains 27% to 45%. Patients with ARDS should be managed with low tidal volume ventilation. Permissive hypercapnea is well tolerated. Conservative fluid strategy can reduce ventilator and hospital days in patients without shock. Prone positioning and neuromuscular blockers reduce mortality in some patients. Early management of ARDS is relevant to emergency medicine. Identifying ARDS patients who should be transferred to an extracorporeal membrane oxygenation center is an important task for emergency providers. PMID:26614238

  12. Management of acute moderate and severe childhood malnutrition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Acute childhood malnutrition affects about a tenth of the world's children under 5 years of age, particularly those living in circumstances of extreme poverty in the developing world. Malnutrition is typically the result of an inadequate diet and is one of the most common diagnoses in children in he...

  13. Hypoxia in Microscopic Tumors

    PubMed Central

    Li, Xiao-Feng; O’Donoghue, Joseph A

    2008-01-01

    Tumor hypoxia has been commonly observed in a broad spectrum of primary solid malignancies. Hypoxia is associated with tumor progression, increased aggressiveness, enhanced metastatic potential and poor prognosis. Hypoxic tumor cells are resistant to radiotherapy and some forms of chemotherapy. Using an animal model, we recently showed that microscopic tumors less than 1 mm diameter were severely hypoxic. In this review, models and techniques for the study of hypoxia in microscopic tumors are discussed. PMID:18384940

  14. Activity of Heme Synthesis Enzymes in the Bone Marrow and Liver of August and Wistar Rats During the Neonatal Period and After Acute Postnatal Hypoxia.

    PubMed

    Kolesnikov, S I; Popova, A S; Krupitskaya, L I; Sinitskii, A I; Kolesnikova, L I

    2015-12-01

    Activity of heme synthesis enzymes in newborn August and Wistar rats was studied after acute hypoxic hypoxia. Daily production of erythrocytes and activities of aminolevulinate synthase, aminolevulinate dehydratase, and heme synthetase were measured in the bone marrow (15-30 min after birth and on days 1 and 3 of life) and liver (day 3 after birth). Hypoxia was followed by a decrease in activity of heme synthesis enzymes in the liver (especially in August rats) and reduction of the daily erythrocyte production (especially in Wistar rats). Our results suggest that the response of heme synthesis enzymes to hypoxic exposure in newborn rats is genetically determined. The observed changes are more pronounced in Wistar rats. PMID:26639471

  15. Hypoxia. 3. Hypoxia and neurotransmitter synthesis

    PubMed Central

    2011-01-01

    Central and peripheral neurons as well as neuroendocrine cells express a variety of neurotransmitters/modulators that play critical roles in regulation of physiological systems. The synthesis of several neurotransmitters/modulators is regulated by O2-requiring rate-limiting enzymes. Consequently, hypoxia resulting from perturbations in O2 homeostasis can affect neuronal functions by altering neurotransmitter synthesis. Two broad categories of hypoxia are frequently encountered: continuous hypoxia (CH) and intermittent hypoxia (IH). CH is often seen during high altitude sojourns, whereas IH is experienced in sleep-disordered breathing with recurrent apneas (i.e., brief, repetitive cessations of breathing). This article presents what is currently known on the effects of both forms of hypoxia on neurotransmitter levels and neurotransmitter synthesizing enzymes in the central and peripheral nervous systems. PMID:21270298

  16. Role of Na+-H+ and Na+-Ca2+ exchange in hypoxia-related acute astrocyte death.

    PubMed

    Bondarenko, Alexander; Svichar, Nataliya; Chesler, Mitchell

    2005-01-01

    Cultured astrocytes do not succumb to hypoxia/zero glucose for up to 24 h, yet astrocyte death following injury can occur within 1 h. It was previously demonstrated that astrocyte loss can occur quickly when the gaseous and interstitial ionic changes of transient brain ischemia are simulated: After a 20-40-min exposure to hypoxic, acidic, ion-shifted Ringer (HAIR), most cells died within 30 min after return to normal saline (i.e., "reperfusion"). Astrocyte death required external Ca2+ and was blocked by KB-R7943, an inhibitor of reversed Na+-Ca2+ exchange, suggesting that injury was triggered by a rise in [Ca2+]i. In the present study, we confirmed the elevation of [Ca2+]i during reperfusion and studied the role of Na+-Ca2+ and Na+-H+ exchange in this process. Upon reperfusion, elevation of [Ca2+]i was detectable by Fura-2 and was blocked by KB-R7943. The low-affinity Ca2+ indicator Fura-FF indicated a mean [Ca2+]i rise to 4.8+/-0.4 microM. Loading astrocytes with Fura-2 provided significant protection from injury, presumably due to the high affinity of the dye for Ca2+. Injury was prevented by the Na+-H+ exchange inhibitors ethyl isopropyl amiloride or HOE-694, and the rise of [Ca2+]i at the onset of reperfusion was blocked by HOE-694. Acidic reperfusion media was also protective. These data are consistent with Na+ loading via Na+-H+ exchange, fostering reversal of Na+-Ca2+ exchange and cytotoxic elevation of [Ca2+]i. The results indicate that mechanisms involved in pH regulation may play a role in the fate of astrocytes following acute CNS injuries. PMID:15390092

  17. Severe Acute Asthma Exacerbation in Children: A Stepwise Approach for Escalating Therapy in a Pediatric Intensive Care Unit

    PubMed Central

    Nievas, I. Federico Fernandez; Anand, Kanwaljeet J. S.

    2013-01-01

    OBJECTIVES An increasing prevalence of pediatric asthma has led to increasing burdens of critical illness in children with severe acute asthma exacerbations, often leading to respiratory distress, progressive hypoxia, and respiratory failure. We review the definitions, epidemiology, pathophysiology, and clinical manifestations of severe acute asthma, with a view to developing an evidence-based, stepwise approach for escalating therapy in these patients. METHODS Subject headings related to asthma, status asthmaticus, critical asthma, and drug therapy were used in a MEDLINE search (1980–2012), supplemented by a manual search of personal files, references cited in the reviewed articles, and treatment algorithms developed within Le Bonheur Children's Hospital. RESULTS Patients with asthma require continuous monitoring of their cardiorespiratory status via noninvasive or invasive devices, with serial clinical examinations, objective scoring of asthma severity (using an objective pediatric asthma score), and appropriate diagnostic tests. All patients are treated with β-agonists, ipratropium, and steroids (intravenous preferable over oral preparations). Patients with worsening clinical status should be progressively treated with continuous β-agonists, intravenous magnesium, helium-oxygen mixtures, intravenous terbutaline and/or aminophylline, coupled with high-flow oxygen and non-invasive ventilation to limit the work of breathing, hypoxemia, and possibly hypercarbia. Sedation with low-dose ketamine (with or without benzodiazepines) infusions may allow better toleration of non-invasive ventilation and may also prepare the patient for tracheal intubation and mechanical ventilation, if indicated by a worsening clinical status. CONCLUSIONS Severe asthma can be a devastating illness in children, but most patients can be managed by using serial objective assessments and the stepwise clinical approach outlined herein. Following multidisciplinary education and training, this

  18. Riboflavin supplementation improves energy metabolism in mice exposed to acute hypoxia.

    PubMed

    Wang, Y P; Wei, J Y; Yang, J J; Gao, W N; Wu, J Q; Guo, C J

    2014-01-01

    This study investigated the effects of riboflavin on energy metabolism in hypoxic mice. Kunming mice were fed diets containing riboflavin at doses of 6, 12, 24 and 48 mg/kg, respectively for 2 weeks before exposure to a simulated altitude of 6000 m for 8 h. Changes of riboflavin status and energy metabolism were assessed biochemically. Simultaneously, a (1)H nuclear magnetic resonance (NMR) based metabolomic technique was used to track the changes of plasma metabolic profiling. It was found that the content of hepatic riboflavin was decreased and erythrocyte glutathione activation coefficient was elevated significantly under hypoxic condition. Meanwhile, increased plasma pyruvate, lactate, beta-hydroxybutyrate and urea, as well as decreased plasma carnitine were observed. Riboflavin supplementation improved riboflavin status remarkably in hypoxic mice and decreased plasma levels of pyruvate, free fatty acids and beta-hydroxybutyrate significantly. Plasma carnitine was increased in response to riboflavin supplementation. Results obtained from (1)H NMR analysis were basically in line with the data from biochemical assays and remarkable changes in plasma taurine, choline and some other metabolites were also indicated. It was concluded that riboflavin requirement was increased under acute hypoxic condition and riboflavin supplementation was effective in improving energy metabolism in hypoxic mice. PMID:24564599

  19. Levetiracetam-induced severe acute granulomatous interstitial nephritis.

    PubMed

    Chau, Katrina; Yong, Jim; Ismail, Kasim; Griffith, Neil; Liu, Michael; Makris, Angela

    2012-06-01

    Granulomatous interstitial nephritis (GIN) is an uncommon cause of renal failure, which may be caused by drugs. Levetiracetam is an increasingly used anti-epileptic medication that is not known to cause renal toxicity in adults. To our knowledge, levetiracetam has not previously been reported as a cause of GIN. We report the case of a 69-year-old woman who developed haemodialysis-requiring acute renal failure after commencement of treatment with levetiracetam, which was shown to be GIN by renal biopsy. She made a complete recovery with cessation of levetiracetam and treatment with steroids. PMID:26069773

  20. The effect of 10 days of heat acclimation on exercise performance in acute hypobaric hypoxia (4350 m).

    PubMed

    White, Ailish C; Salgado, Roy M; Astorino, Todd A; Loeppky, Jack A; Schneider, Suzanne M; McCormick, James J; McLain, Trisha A; Kravitz, Len; Mermier, Christine M

    2016-01-01

    To examine the effect ("cross-tolerance") of heat acclimation (HA) on exercise performance upon exposure to acute hypobaric hypoxia (4350 m). Eight male cyclists residing at 1600 m performed tests of maximal aerobic capacity (VO2max) at 1600 m and 4350 m, a 16 km time-trial at 4350 m, and a heat tolerance test at 1600 m before and after 10 d HA at 40°C, 20% RH. Resting blood samples were obtained pre-and post- HA to estimate changes in plasma volume (ΔPV). Successful HA was indicated by significantly lower exercise heart rate and rectal temperature on day 10 vs. day 1 of HA and during the heat tolerance tests. Heat acclimation caused a 1.9% ΔPV, however VO2max was not significantly different at 1600 m or 4350 m. Time-trial cycling performance improved 28 sec after HA (p = 0.07), suggesting a possible benefit for exercise performance at acute altitude and that cross-tolerance between these variables may exist in humans. These findings do not clearly support the use of HA to improve exercise capacity and performance upon acute hypobaric hypoxia, however they do indicate that HA is not detrimental to either exercise capacity or performance. PMID:27227084

  1. The effect of 10 days of heat acclimation on exercise performance in acute hypobaric hypoxia (4350 m)

    PubMed Central

    White, Ailish C.; Salgado, Roy M.; Astorino, Todd A.; Loeppky, Jack A.; Schneider, Suzanne M.; McCormick, James J.; McLain, Trisha A.; Kravitz, Len; Mermier, Christine M.

    2016-01-01

    ABSTRACT To examine the effect (“cross-tolerance”) of heat acclimation (HA) on exercise performance upon exposure to acute hypobaric hypoxia (4350 m). Eight male cyclists residing at 1600 m performed tests of maximal aerobic capacity (VO2max) at 1600 m and 4350 m, a 16 km time-trial at 4350 m, and a heat tolerance test at 1600 m before and after 10 d HA at 40°C, 20% RH. Resting blood samples were obtained pre-and post- HA to estimate changes in plasma volume (ΔPV). Successful HA was indicated by significantly lower exercise heart rate and rectal temperature on day 10 vs. day 1 of HA and during the heat tolerance tests. Heat acclimation caused a 1.9% ΔPV, however VO2max was not significantly different at 1600 m or 4350 m. Time-trial cycling performance improved 28 sec after HA (p = 0.07), suggesting a possible benefit for exercise performance at acute altitude and that cross-tolerance between these variables may exist in humans. These findings do not clearly support the use of HA to improve exercise capacity and performance upon acute hypobaric hypoxia, however they do indicate that HA is not detrimental to either exercise capacity or performance. PMID:27227084

  2. Postnatal loss of brainstem serotonin neurones compromises the ability of neonatal rats to survive episodic severe hypoxia.

    PubMed

    Cummings, Kevin J; Hewitt, Julie C; Li, Aihua; Daubenspeck, John A; Nattie, Eugene E

    2011-11-01

    understanding the aetiology of the sudden infant death syndrome (SIDS), in which there is medullary 5-HT deficiency and in some cases evidence of severe hypoxia and failed autoresuscitation. PMID:21911619

  3. Preclinical evidence of mitochondrial nicotinamide adenine dinucleotide as an effective alarm parameter under hypoxia

    NASA Astrophysics Data System (ADS)

    Shi, Hua; Sun, Nannan; Mayevsky, Avraham; Zhang, Zhihong; Luo, Qingming

    2014-01-01

    Early detection of tissue hypoxia in the intensive care unit is essential for effective treatment. Reduced nicotinamide adenine dinucleotide (NADH) has been suggested to be the most sensitive indicator of tissue oxygenation at the mitochondrial level. However, no experimental evidence comparing the kinetics of changes in NADH and other physiological parameters has been provided. The aim of this study is to obtain the missing data in a systematic and reliable manner. We constructed four acute hypoxia models, including hypoxic hypoxia, hypemic hypoxia, circulatory hypoxia, and histogenous hypoxia, and measured NADH fluorescence, tissue reflectance, cerebral blood flow, respiration, and electrocardiography simultaneously from the induction of hypoxia until death. We found that NADH was not always the first onset parameter responding to hypoxia. The order of responses was mainly affected by the cause of hypoxia. However, NADH reached its alarm level earlier than the other monitored parameters, ranging from several seconds to >10 min. As such, we suggest that the NADH can be used as a hypoxia indicator, although the exact level that should be used must be further investigated. When the NADH alarm is detected, the body still has a chance to recover if appropriate and timely treatment is provided.

  4. Cardiac responses to hypoxia and reoxygenation in Drosophila.

    PubMed

    Zarndt, Rachel; Piloto, Sarah; Powell, Frank L; Haddad, Gabriel G; Bodmer, Rolf; Ocorr, Karen

    2015-12-01

    An adequate supply of oxygen is important for the survival of all tissues, but it is especially critical for tissues with high-energy demands, such as the heart. Insufficient tissue oxygenation occurs under a variety of conditions, including high altitude, embryonic and fetal development, inflammation, and thrombotic diseases, often affecting multiple organ systems. Responses and adaptations of the heart to hypoxia are of particular relevance in human cardiovascular and pulmonary diseases, in which the effects of hypoxic exposure can range in severity from transient to long-lasting. This study uses the genetic model system Drosophila to investigate cardiac responses to acute (30 min), sustained (18 h), and chronic (3 wk) hypoxia with reoxygenation. Whereas hearts from wild-type flies recovered quickly after acute hypoxia, exposure to sustained or chronic hypoxia significantly compromised heart function upon reoxygenation. Hearts from flies with mutations in sima, the Drosophila homolog of the hypoxia-inducible factor alpha subunit (HIF-α), exhibited exaggerated reductions in cardiac output in response to hypoxia. Heart function in hypoxia-selected flies, selected over many generations for survival in a low-oxygen environment, revealed reduced cardiac output in terms of decreased heart rate and fractional shortening compared with their normoxia controls. Hypoxia-selected flies also had smaller hearts, myofibrillar disorganization, and increased extracellular collagen deposition, consistent with the observed reductions in contractility. This study indicates that longer-duration hypoxic insults exert deleterious effects on heart function that are mediated, in part, by sima and advances Drosophila models for the genetic analysis of cardiac-specific responses to hypoxia and reoxygenation. PMID:26377557

  5. Influence of age upon the cerebral metabolic changes induced by acute hypoxia on the synaptosomes from dog brain.

    PubMed

    Benzi, G; Arrigoni, E; Agnoli, A; Raimondo, S; Fulle, D; Pastoris, O; Curti, D; Villa, R F

    1982-01-01

    The synaptosomal fraction obtained from the motor area of the cerebral cortex of normocapnic, normoxic or hypoxic "young adult," "mature" and "senescent" beagle dogs is incubated and analyzed for : ATP, ADP, AMP, creatine phosphate, pyruvate and lactate. The data are compared with those obtained from the whole controlateral cortical motor area, by the surface freezing technique. After hypoxic hypoxia /15 min; PaO2 = 17-19 mm Hg), the metabolite contents and ratios are differently affected by ageing when the evaluations are performed in the incubated synaptosomal preparation or in the controlateral whole cerebral tissue. In fact, ageing does not affect so much the cerebral changes that occur in the overall energetic state during the hypoxic assault in vivo, but rather those that the synaptosomes remember the tend to reverse during the subsequent incubation in vitro. The protective action of several drugs on the synaptosomal phosphorylation state is tested. Phenobarbital shows a quite broad, age-independent spectrum of action. (-)Eburnamonine and dihydroergocristine exhibits a more limited, age-dependent effectiveness, but are devoid of anesthetic action. Papaverine proves unable to affect the tested biochemical parameters. PMID:6807702

  6. Physiological responses of the ghost shrimp Neotrypaea uncinata (Milne Edwards 1837) (Decapoda: Thalassinidea) to oxygen availability and recovery after severe environmental hypoxia.

    PubMed

    Leiva, Félix P; Urbina, Mauricio A; Cumillaf, Juan Pablo; Gebauer, Paulina; Paschke, Kurt

    2015-11-01

    Hypoxia is a common and widespread phenomenon in aquatic ecosystems, imposing a significant challenge for the animals that inhabit such waters. In different habitats, however, the characteristics of these hypoxic events may differ, therefore imposing different challenges. We investigated the tolerance of adult ghost shrimp Neotrypaea uncinata (an intertidal mudflat dweller) to different partial pressures of oxygen (pO2), severe hypoxia (2 kPa) and recovery from hypoxia after different exposure times, mimicking the natural tidal cycle (6 h and 12 h). We calculated critical oxygen tension and categorize the adult ghost shrimps as oxyregulators (R value=75.27%). All physiological measurements (metabolic rate, oxyhemocyanin, hemolymph protein and lactate concentrations) were affected by exposure to low partial pressures of oxygen, but most of them recovered (with exception of metabolic rate) control values (21 kPa) after 6h under normoxic conditions. Low metabolic rate, high release of hemolymphatic proteins and anaerobic metabolism are suggested as response mechanisms to overcome hypoxic events during low tide. PMID:26212148

  7. Acute hypoxia differentially affects the NMDA receptor NR1, NR2A and NR2B subunit mRNA levels in the developing chick optic tectum: stage-dependent plasticity in the 2B-2A ratio.

    PubMed

    Vacotto, Marina; Rapacioli, Melina; Flores, Vladimir; de Plazas, Sara Fiszer

    2010-10-01

    It is known that the NMDA-R NR1 subunit is needed for the receptor activity and that under hypoxia the evolution toward apoptosis or neuronal survival depends on the balance NR2A/NR2B subunits. This paper analyzes the effect of acute hypoxia on the above mentioned subunits mRNAs during development. The mean percentage of NR1+ neurons displayed the higher plasticity during development while the NR2A+ neurons the higher stability. Acute hypoxia increased the mean percentage of NR1+ and NR2B+ neurons at ED12 but only that of NR1+ neurons at ED18. Acute hypoxia increased the levels of expression of NR1 and NR2B mRNAs at ED12 without changes in the NR2A mRNA. During early stages there is a higher sensitivity to change the subunits mRNA levels under a hypoxic treatment. At ED12 acute hypoxia increased the probability of co-expression of the NR1-NR2A and NR1-NR2B subunits combinations, the level of NR1 and NR2B and the ratio NR2B/NR2A. These conditions facilitate the evolution towards apoptosis. PMID:20596770

  8. Home-based therapy for severe acute malnutrition with ready-to-use food

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Severe acute malnutrition is a devastating condition afflicting children under 5 years in many developing countries, but concentrated in sub-Saharan Africa. This paper examines the development of home-based lipid-nutrient therapeutic foods for the treatment of acute malnutrition in sub-Saharan Afric...

  9. Systemic oxidative-nitrosative-inflammatory stress during acute exercise in hypoxia; implications for microvascular oxygenation and aerobic capacity.

    PubMed

    Woodside, John D S; Gutowski, Mariusz; Fall, Lewis; James, Philip E; McEneny, Jane; Young, Ian S; Ogoh, Shigehiko; Bailey, Damian M

    2014-12-01

    Exercise performance in hypoxia may be limited by a critical reduction in cerebral and skeletal tissue oxygenation, although the underlying mechanisms remain unclear. We examined whether increased systemic free radical accumulation during hypoxia would be associated with elevated microvascular deoxygenation and reduced maximal aerobic capacity (V̇O2 max ). Eleven healthy men were randomly assigned single-blind to an incremental semi-recumbent cycling test to determine V̇O2 max in both normoxia (21% O2) and hypoxia (12% O2) separated by a week. Continuous-wave near-infrared spectroscopy was employed to monitor concentration changes in oxy- and deoxyhaemoglobin in the left vastus lateralis muscle and frontal cerebral cortex. Antecubital venous blood samples were obtained at rest and at V̇O2 max to determine oxidative (ascorbate radical by electron paramagnetic resonance spectroscopy), nitrosative (nitric oxide metabolites by ozone-based chemiluminescence and 3-nitrotyrosine by enzyme-linked immunosorbent assay) and inflammatory stress biomarkers (soluble intercellular/vascular cell adhesion 1 molecules by enzyme-linked immunosorbent assay). Hypoxia was associated with increased cerebral and muscle tissue deoxygenation and lower V̇O2 max (P < 0.05 versus normoxia). Despite an exercise-induced increase in oxidative-nitrosative-inflammatory stress, hypoxia per se did not have an additive effect (P > 0.05 versus normoxia). Consequently, we failed to observe correlations between any metabolic, haemodynamic and cardiorespiratory parameters (P > 0.05). Collectively, these findings suggest that altered free radical metabolism cannot explain the elevated microvascular deoxygenation and corresponding lower V̇O2 max in hypoxia. Further research is required to determine whether free radicals when present in excess do indeed contribute to the premature termination of exercise in hypoxia. PMID:25344270

  10. Acute intermittent hypoxia induced phrenic long-term facilitation despite increased SOD1 expression in a rat model of ALS.

    PubMed

    Nichols, Nicole L; Satriotomo, Irawan; Harrigan, Daniel J; Mitchell, Gordon S

    2015-11-01

    Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease characterized by motor neuron death. Since most ALS patients succumb to ventilatory failure from loss of respiratory motor neurons, any effective ALS treatment must preserve and/or restore breathing capacity. In rats over-expressing mutated super-oxide dismutase-1 (SOD1(G93A)), the capacity to increase phrenic motor output is decreased at disease end-stage, suggesting imminent ventilatory failure. Acute intermittent hypoxia (AIH) induces phrenic long-term facilitation (pLTF), a form of spinal respiratory motor plasticity with potential to restore phrenic motor output in clinical disorders that compromise breathing. Since pLTF requires NADPH oxidase activity and reactive oxygen species (ROS) formation, it is blocked by NADPH oxidase inhibition and SOD mimetics in normal rats. Thus, we hypothesized that SOD1(G93A) (mutant; MT) rats do not express AIH-induced pLTF due to over-expression of active mutant superoxide dismutase-1. AIH-induced pLTF and hypoglossal (XII) LTF were assessed in young, pre-symptomatic and end-stage anesthetized MT rats and age-matched wild-type littermates. Contrary to predictions, pLTF and XII LTF were observed in MT rats at all ages; at end-stage, pLTF was actually enhanced. SOD1 levels were elevated in young and pre-symptomatic MT rats, yet superoxide accumulation in putative phrenic motor neurons (assessed with dihydroethidium) was unchanged; however, superoxide accumulation significantly decreased at end-stage. Thus, compensatory mechanisms appear to maintain ROS homoeostasis until late in disease progression, preserving AIH-induced respiratory plasticity. Following intrathecal injections of an NADPH oxidase inhibitor (apocynin; 600 μM; 12 μL), pLTF was abolished in pre-symptomatic, but not end-stage MT rats, demonstrating that pLTF is NADPH oxidase dependent in pre-symptomatic, but NADPH oxidase independent in end-stage MT rats. Mechanisms

  11. [Artificial nutrition in severe acute pancreatitis: an evolving concept].

    PubMed

    Mangiante, Gerardo; Zugni, Chiara; Chimetto, Andrea; Rossi, Michele; Campagnaro, Tommaso; Biasiutti, Carlo

    2007-01-01

    We reviewed our series of consecutive cases of severe pancreatitis observed from 2002 to 2004, in order to verify how our actual therapeutic strategy improved prognosis. Seventeen patients with diagnosis of severe pancreatitis (SP) were admitted. On presumption of SP we inserted a naso-jejunal self-propelling feeding tube (SPT) in all but one patients, and an early enteral nutrition ( EEN ) was started. Severity of pancreatitis has been scored by APACHE II (> 8), IMRIE (> or = 3), and Balthazar Computed Tomography findings (> 30% necrosis). We always used a polymeric diet added with glutamine and fibres at initial rate of 20-30 ml/h until achievement of a full regimen of EEN, based on Harris-Benedict formula but no more than 30 kcal/kg/day. Only one patient has been submitted to surgical removal of infected necrosis. A patient died (5.8%) by dis-metabolic and septic state. From our experience we can state EEN is safe and useful to determine a favourable outcome on this dismal pathology, preserving the patient from infection, without significative alterations of nutritional index. PMID:17361934

  12. Severe Acute Pulmonary Toxicity Associated with Brentuximab in a Patient with Refractory Hodgkin's Lymphoma

    PubMed Central

    Sabet, Yasmin; Ramirez, Saul; Rosell Cespedes, Elizabeth; Rensoli Velasquez, Marimer; Porres-Muñoz, Mateo; Gaur, Sumit; Figueroa-Casas, Juan B.; Porres-Aguilar, Mateo

    2016-01-01

    Acute pulmonary toxicity associated with brentuximab appears to be a rare but serious adverse effect that can be potentially fatal. We report the case of a twenty-nine-year-old female with Hodgkin's lymphoma who was treated with brentuximab and later presented with severe acute pulmonary toxicity; she improved after the discontinuation of brentuximab and administration of antibiotics and glucocorticoid therapy. Currently there is very little data in the literature in regard to the clinical manifestations and characteristics of patients taking brentuximab and the potential development of acute severe pulmonary toxicity, as well as the appropriate therapeutic approach, making this particular case of successful treatment and resolution unique. PMID:27190667

  13. Celiac disease unmasked by acute severe iron deficiency anemia

    PubMed Central

    Meseeha, Marcelle G.; Attia, Maximos N.; Kolade, Victor O.

    2016-01-01

    The prevalence of celiac disease (CD) appears to be increasing in the United States. However, the proportion of new CD cases with atypical presentations is also rising. We present the case of a 49-year-old woman who was diagnosed with CD in the setting of new, severe iron-deficiency anemia, 13 years into treatment of diarrhea-predominant irritable bowel syndrome associated with chronic mildly elevated liver function tests. While CD and iron deficiency anemia are common, this is a rare presentation of CD. PMID:27406450

  14. Celiac disease unmasked by acute severe iron deficiency anemia.

    PubMed

    Meseeha, Marcelle G; Attia, Maximos N; Kolade, Victor O

    2016-01-01

    The prevalence of celiac disease (CD) appears to be increasing in the United States. However, the proportion of new CD cases with atypical presentations is also rising. We present the case of a 49-year-old woman who was diagnosed with CD in the setting of new, severe iron-deficiency anemia, 13 years into treatment of diarrhea-predominant irritable bowel syndrome associated with chronic mildly elevated liver function tests. While CD and iron deficiency anemia are common, this is a rare presentation of CD. PMID:27406450

  15. Acute Hypoxia Decreases E. coli LPS-Induced Cytokine Production and NF-κB Activation in Alveolar Macrophages*

    PubMed Central

    Matuschak, George M.; Nayak, Ravi; Doyle, Timothy M.; Lechner, Andrew J.

    2010-01-01

    Reductions in alveolar oxygenation during lung hypoxia/reoxygenation (H/R) injury are common after gram-negative endotoxemia. However, the effects of H/R on endotoxin-stimulated cytokine production by alveolar macrophages are unclear and may depend upon thresholds for hypoxic oxyradical generation in situ. Here TNF-α and IL-β production were determined in rat alveolar macrophages stimulated with E. coli lipopolysaccharide (LPS, serotype O55:B5) while exposed to either normoxia for up to 24 h, to brief normocarbic hypoxia (1.5 h at an atmospheric PO2 = 10 ± 2 mm Hg), or to combined H/R. LPS-induced TNF-α and IL-β were reduced at the peak of hypoxia and by reoxygenation in LPS + H/R cells (P < 0.01) compared with normoxic controls despite no changes in reduced glutathione (GSH) or in PGE2 production. Both TNF-α mRNA and NF-κB activation were reduced by hypoxia that suppressed superoxide anion generation. Thus, dynamic reductions in the ambient PO2 of alveolar macrophages that do not deplete GSH suppress LPS-induced TNF-α expression, IL-β production, and NF-κB activation even as oxyradical production is decreased. PMID:20470909

  16. Severe acute respiratory syndrome (SARS): lessons learnt in Hong Kong.

    PubMed

    Hui, David S

    2013-08-01

    Many healthcare workers were infected while looking after the SARS patients on the medical wards in 2003. The high infectivity of the SARS coronavirus with peak viral load on day 10 of illness when patients were ill, overcrowding of the old medical wards with low air changes/hr (ACH), and aerosol-generating procedures while resuscitating the patients were the major factors. Procedures reported to present an increased risk of SARS transmission include tracheal intubation, non-invasive ventilation, tracheotomy and manual ventilation before intubation whereas oxygen therapy and bed distance <1 m were also implicated. Studies based on laser visualization technique with smoke particles as smokers in the human patient simulator has shown that oxygen therapy via Hudson mask and nasal cannula could disperse exhaled air of patients to 0.4 and 1 m respectively whereas jet nebulizer could disperse exhaled air >0.8 m from the patient. Bigger isolation rooms with 16 ACH are more effective than smaller isolation rooms with 12 ACH in removing exhaled air and preventing room contamination but at the expense of more noise and electricity consumption. Non-invasive ventilation via face masks and single circuit can disperse exhaled air from 0.4 to 1 m. Both higher inspiratory pressures and use of whisper swivel device (to facilitate carbon dioxide removal) could increase the exhaled air leakage and isolation room contamination during on-invasive ventilation. Addition of a viral-bacterial filter during manual ventilation by bagging may reduce the exhaled air leakage forward and yet increase the sideway leakage. N95 mask was more effective than surgical mask in preventing expelled air leakage during patient's coughing but there was still significant sideway leakage to 15 cm. Clinicians should be aware of air leakage from the various face masks and adopt strict infection control measures during resuscitation of patients with severe respiratory infections. Carefully designed clinical

  17. Biopsy-proven drug-induced tubulointerstitial nephritis in a patient with acute kidney injury and alcoholic severe acute pancreatitis.

    PubMed

    Yoshioka, Wakako; Mori, Takayasu; Nagahama, Kiyotaka; Tamura, Teiichi

    2013-01-01

    We report a 49-year-old man with alcoholic severe acute pancreatitis (SAP) complicated by drug-induced acute tubulointerstitial nephritis (DI-AIN). Oliguria persisted and became anuric again on day 17 despite improvement of pancreatitis. He presented rash, fever and eosinophilia from day 20. Renal biopsy was performed for dialysis-dependent acute kidney injury (AKI), DI-AIN was revealed, and prompt use of corticosteroids fully restored his renal function. This diagnosis might be missed because it is difficult to perform renal biopsy in such a clinical situation. If the patient's general condition allows, renal biopsy should be performed and reversible AKI must be distinguished from many cases of irreversible AKI complicated by SAP. This is the first report of biopsy-proven DI-AIN associated with SAP, suggesting the importance of biopsy for distinguishing DI-AIN in persisting AKI of SAP. PMID:23645698

  18. [Acute severe coxsackie virus B myocarditis of pseudonecrotic form. Apropos of 2 cases].

    PubMed

    Beard, T; Boudjemaa, B; Carrié, D; Chakra, G; Ferrières, J; Delay, M; Bernadet, P

    1993-05-01

    This study reports two cases of acute severe Coxsackie virus B4 myocarditis in which the immediate clinical signs suggested the acute phase of myocardial infarction, apparently antero-lateral in the first case in a context of cardiogenic shock and infero-lateral in the second case, in the context of acute pulmonary edema. Both cases were characterized by the severity of the initial signs. Numerous other cases of acute Coxsackie virus B myocarditis, simulating myocardial infarction, have been reported in the literature and these contexts deserve to be recognized earlier as they call for specific treatment. The immediate outcome was favorable in both cases but required massive cardiological intensive care in the first patient. Long term follow-up was excellent. PMID:8396381

  19. Rapidly Progressing Severe Cutaneous Adverse Reaction With Acute Kidney Injury After Drug Exposure: An Uncommon Presentation.

    PubMed

    Rodgers, Bradley K; Kumar, Avinash B

    2016-01-01

    Toxic epidermal necrolysis syndrome (TEN) is a rare severe cutaneous adverse drug reaction that involves skin and mucous membranes. We describe a case of TEN presenting with stage III acute kidney injury, rhabdomyolysis, and acute respiratory failure likely triggered by allopurinol for recently diagnosed gout. Prompt diagnosis, multidisciplinary management, including aggressive resuscitation, cardiorespiratory support, intravenous immunoglobulin therapy, and daily wound care resulted in a positive outcome despite a predicted mortality greater than 60%. Although allopurinol is a known triggering agent, TEN presenting with rhabdomyolysis and acute kidney injury is rare. PMID:24832386

  20. A method for measuring brain partial pressure of oxygen in unanesthetized unrestrained subjects: the effect of acute and chronic hypoxia on brain tissue PO2

    PubMed Central

    Ortiz-Prado, E.; Natah, Siraj; Srinivasan, Sathyanarayanan; Dunn, Jeff F.

    2011-01-01

    The level of tissue oxygenation provides information related to the balance between oxygen delivery, oxygen utilization, tissue reactivity and morphology during physiological conditions. Tissue partial pressure of oxygen (PtO2) is influenced by the use of anesthesia or restraint. These factors may impact the absolute level of PtO2. In this study we present a novel fibre optic method to measure brain PtO2. This method can be used in unanesthetized, unrestrained animals, provides absolute values for PO2, has a stable calibration, does not consume oxygen and is MRI compatible. Brain PtO2 was studied during acute hypoxia, as well as before and after 28 days of high altitude acclimatization. A sensor was chronically implanted in the frontal cortex of 8 Wistar rats. It is comprised of a fiber optic probe with a tip containing material that fluoresces with an oxygen dependent lifetime. Brain PtO2 declines by 80% and 76% pre- and post-acclimatization respectively, when the fraction of inspired oxygen declines from 0.21 to 0.08. In addition, a linear relationship between brain PtO2 and inspired O2 levels was demonstrated r2=0.98 and r2=0.99 (pre- and post-acclimatization). Hypoxia acclimatization resulted in an increase in the overall brain PtO2 by approximately 35%. This paper demonstrates the use of a novel chronically implanted fibre optic based sensor for measuring absolute PtO2. It shows a very strong linear relationship in awake animals between inspired O2 and tissue O2, and shows that there is a proportional increase in PtO2 over a range of inspired values after exposure to chronic hypoxia. PMID:20817029

  1. Human placental renin-angiotensin system in normotensive and pre-eclamptic pregnancies at high altitude and after acute hypoxia-reoxygenation insult.

    PubMed

    Kurlak, Lesia O; Mistry, Hiten D; Cindrova-Davies, Tereza; Burton, Graham J; Broughton Pipkin, Fiona

    2016-03-01

    A functioning placental renin-angiotensin system (RAS) appears necessary for uncomplicated pregnancy and is present during placentation, which occurs under low oxygen tensions. Placental RAS is increased in pre-eclampsia (PE), characterised by placental dysfunction and elevated oxidative stress. We investigated the effect of high altitude hypoxia on the RAS and hypoxia-inducible factors (HIFs) by measuring mRNA and protein expression in term placentae from normotensive (NT) and PE women who delivered at sea level or above 3100 m, using an explant model of hypoxia-reoxygenation to assess the impact of acute oxidative stress on the RAS and HIFs. Protein levels of prorenin (P = 0.049), prorenin receptor (PRR; P = 0.0004), and angiotensin type 1 receptor (AT1R, P = 0.006) and type 2 receptor (AT2R, P = 0.002) were all significantly higher in placentae from NT women at altitude, despite mRNA expression being unaffected. However, mRNA expression of all RAS components was significantly lower in PE at altitude than at sea level, yet PRR, angiotensinogen (AGT) and AT1R proteins were all increased. The increase in transcript and protein expression of all the HIFs and NADPH oxidase 4 seen in PE compared to NT at sea level was blunted at high altitude. Experimentally induced oxidative stress stimulated AGT mRNA (P = 0.04) and protein (P = 0.025). AT1R (r = 0.77, P < 0.001) and AT2R (r = 0.81, P < 0.001) mRNA both significantly correlated with HIF-1β, whilst AT2R also correlated with HIF-1α (r = 0.512, P < 0.013). Our observations suggest that the placental RAS is responsive to changes in tissue oxygenation: this could be important in the interplay between reactive oxygen species as cell-signalling molecules for angiogenesis and hence placental development and function. PMID:26574162

  2. Recurrent Acute Decompensated Heart Failure Owing to Severe Iron Deficiency Anemia Caused by Inappropriate Habitual Bloodletting

    PubMed Central

    Lim, Woo-Hyun; Kim, Hack-Lyoung; Kim, Ki-Hwan; Na, Sang Hoon; Lee, Hyun-Jung; Kang, Eun Gyu; Seo, Jae-Bin; Chung, Woo-Young; Zo, Joo-Hee; Hong, Jung Ae; Kim, Kwangyoun; Kim, Myung-A

    2015-01-01

    A 68-year-old woman visited the emergency department twice with symptoms of acute heart failure including shortness of breath, general weakness, and abdominal distension. Laboratory findings showed extremely low level of serum hemoglobin at 1.4 g/dL. Echocardiographic examination demonstrated dilated left ventricular cavity with systolic dysfunction and moderate amount of pericardial effusion. In this patient, acute heart failure due to severe iron deficiency anemia was caused by inappropriate habitual bloodletting. PMID:26755934

  3. Severe Acute Respiratory Syndrome and the Delivery of Continuing Medical Education: Case Study from Toronto

    ERIC Educational Resources Information Center

    Davis, Dave; Ryan, David; Sibbald, Gary; Rachlis, Anita; Davies, Sharon; Manchul, Lee; Parikh, Sagar

    2004-01-01

    Introduction: Severe acute respiratory syndrome (SARS) struck Toronto in the spring of 2003, causing many deaths, serious morbidity, forced quarantine of thousands of individuals, and the closure of all provincial hospitals for several weeks. Given the direction by public health authorities to cancel or postpone all continuing medical education…

  4. Tissue hypoxia during ischemic stroke: adaptive clues from hypoxia-tolerant animal models.

    PubMed

    Nathaniel, Thomas I; Williams-Hernandez, Ashley; Hunter, Anan L; Liddy, Caroline; Peffley, Dennis M; Umesiri, Francis E; Imeh-Nathaniel, Adebobola

    2015-05-01

    The treatment and prevention of hypoxic/ischemic brain injury in stroke patients remain a severe and global medical issue. Numerous clinical studies have resulted in a failure to develop chemical neuroprotection for acute, ischemic stroke. Over 150 estimated clinical trials of ischemic stroke treatments have been done, and more than 200 drugs and combinations of drugs for ischemic and hemorrhagic strokes have been developed. Billions of dollars have been invested for new scientific breakthroughs with only limited success. The revascularization of occluded cerebral arteries such as anti-clot treatments of thrombolysis has proven effective, but it can only be used in a 3-4.5h time frame after the onset of a stroke, and not for every patient. This review is about novel insights on how to resist tissue hypoxia from unconventional animal models. Ability to resist tissue hypoxia is an extraordinary ability that is not common in many laboratory animals such as rat and mouse models. For example, we can learn from a naked mole-rat, Chrysemys picta, how to actively regulate brain metabolic activity to defend the brain against fluctuating oxygen tension and acute bouts of oxidative stress following the onset of a stroke. Additionally, a euthermic arctic ground squirrel can teach us how the brain of a stroke patient can remain well oxygenated during tissue hypoxia with no evidence of cellular stress. In this review, we discuss how these animals provide us with a system to gain insight into the possible mechanisms of tissue hypoxia/ischemia. This issue is of clinical significance to stroke patients. We describe specific physiological and molecular adaptations employed by different animals' models of hypoxia tolerance in aquatic and terrestrial environments. We highlight how these adaptations might provide potential clues on strategies to adapt for the clinical management of tissue hypoxia during conditions such as stroke where oxygen demand fails to match the supply. PMID

  5. The Glomerulus and Serum Sickness in Experimental Hypoxia

    PubMed Central

    Spear, G. S.; Kihara, I.

    1972-01-01

    The effect of prolonged continuous hypoxia with polycythaemia on the rabbit glomerulus was studied by light microscopy and their effect on experimental serum sickness in rabbits was studied by light and immunofluorescent microscopy. Engorgement and enlargement were the principal effects on the glomerulus of hypoxia and polycythaemia, but prominence of the mesangium and focal segmental sclerosis and hypercellularity sometimes occurred. The results of the studies on serum sickness suggested that prolonged hypoxia with polycythaemia did not diminish antibody formation, reactivity of antibody with antigen, or rapid antigen clearance; in fact antigen was cleared more rapidly in hypoxic animals. Chronic hypoxia and polycythaemia did not prevent acute serum sickness including acute glomerulonephritis. The incidence and severity of acute glomerulonephritis, however, may have been diminished whereas the incidence and severity of other visceral involvement by acute serum sickness was not. Although the experimental groups were not large, the possible implications of the data are important. Focal segmental glomerular sclerosis and hypercellularity, and mesangial prominence, to our knowledge have not previously been reported in association with chronic experimental hypoxia and polycythaemia. These lesions resembled some glomerular lesions of cyanotic congenital heart disease. Decrease in glomerulonephritis under conditions in which hydrostatic pressure in the glomerulus is presumably elevated and the glomerulus is subject to injury in some respects would be contrary to expectation. Finally, selective decrease in the glomerulonephritic but not the other lesions of acute serum sickness by altering non-immunological general experimental conditions would be highly unusual. More extensive studies are indicated. ImagesFigs. 1-5Figs. 6-12 PMID:5055712

  6. A study of the clinical profile of acute pancreatitis and its correlation with severity indices

    PubMed Central

    Vengadakrishnan, K.; Koushik, A. K.

    2015-01-01

    Background Acute pancreatitis is a common disease with wide clinical variation and its incidence is increasing. Acute pancreatitis may vary in severity, from mild self-limiting pancreatic inflammation to pancreatic necrosis with life-threatening sequelae. Severity of acute pancreatitis is linked to the presence of systemic organ dysfunctions and/or necrotizing pancreatitis. Aim and objectives The present study was aimed to assess the clinical profile of acute pancreatitis and to assess the efficacy of various severity indices in predicting the outcome of patients. Methodology This was a prospective study done in Sri Ramachandra Medical College and Hospital from April 2012–September 2014. All patients with a diagnosis of acute pancreatitis were included in this study. Along with routine lab parameters, serum amylase, lipase, lipid profile, calcium, CRP, LDH, CT abdomen, CXR and 2D Echo was done for all patients. Results A total of 110 patients were analysed. 50 patients required Intensive care, among them 9 patients (18%) died. 20 patients (18.2%) had MODS, 15 patients (13.6%) had pleural effusion, 9 patients (8.2%) had pseudocyst, 2 patients(1.8%) had hypotension, 2 patients(1.8%) had ARDS and 2 patients(1.8%) had DKA. In relation to various severity indices, high score of CRP, LDH and CT severity index was associated with increased morbidity and mortality. 15 patients (13.6%) underwent open necrosectomy surgery, 3 patients (2.7%) underwent laparoscopic necrosectomy and 7 patients (6.4%) were tried step up approach but could not avoid surgery. Step up approach and surgery did not have a significant reduction in the mortality. Conclusion Initial assessment of severity by CRP, LDH and lipase could be reliable indicators of outcome in acute pancreatitis PMID:26715920

  7. Soluble CD163 is increased in patients with acute pancreatitis independent of disease severity.

    PubMed

    Karrasch, Thomas; Brünnler, Tanja; Hamer, Okka W; Schmid, Karin; Voelk, Markus; Herfarth, Hans; Buechler, Christa

    2015-10-01

    Macrophages are crucially involved in the pathophysiology of acute pancreatitis. Soluble CD163 (sCD163) is specifically released from macrophages and systemic levels are increased in inflammatory diseases. Here, sCD163 was measured in serum of 50 patients with acute pancreatitis to find out possible associations with disease activity. Admission levels of systemic sCD163 were nearly three-fold higher in patients with acute pancreatitis compared to controls. In patients sCD163 did not correlate with C-reactive protein and leukocyte count as established markers of inflammation. Levels were not associated with disease severity assessed by the Schroeder score, Balthazar score, Acute Physiology, Age, and Chronic Health Evaluation (Apache) II score and peripancreatic necrosis score. Soluble CD163 was not related to complications of acute pancreatitis. These data show that serum sCD163 is increased in acute pancreatitis indicating activation of macrophages but is not associated with disease severity and outcome. PMID:26209500

  8. Acute intermittent hypoxia-induced expression of brain-derived neurotrophic factor is disrupted in the brainstem of methyl-CpG-binding protein 2 null mice.

    PubMed

    Vermehren-Schmaedick, A; Jenkins, V K; Knopp, S J; Balkowiec, A; Bissonnette, J M

    2012-03-29

    Rett syndrome is a neurodevelopmental disorder caused by loss-of-function mutations in the gene encoding the transcription factor methyl-CpG-binding protein 2 (MeCP2). One of its targets is the gene encoding brain-derived neurotrophic factor (bdnf). In vitro studies using cultured neurons have produced conflicting results with respect to the role of MeCP2 in BDNF expression. Acute intermittent hypoxia (AIH) induces plasticity in the respiratory system characterized by long-term facilitation of phrenic nerve amplitude. This paradigm induces an increase in BDNF protein. We hypothesized that AIH leads to augmentation of BDNF transcription in respiratory-related areas of the brainstem and that MeCP2 is necessary for this process. Wild-type and mecp2 null (mecp2(-/y)) mice were subjected to three 5-min episodes of exposure to 8% O(2)/4% CO(2)/88% N(2), delivered at 5-min intervals. Normoxia control wild-type and mecp2 null mice were exposed to room air for the total length of time, that is, 30 min. Following a recovery in room air, the pons and medulla were rapidly removed. Expression of BDNF protein and transcripts were determined by ELISA and quantitative PCR, respectively. AIH induced a significant increase in BDNF protein in the pons and medulla, and in mRNA transcript levels in the pons of wild-type animals. In contrast, there were no significant changes in either BDNF protein or transcripts in the pons or medulla of mice lacking MeCP2. The results indicate that MeCP2 is required for regulation of BDNF expression by acute intermittent hypoxia in vivo. PMID:22297041

  9. Acute intermittent hypoxia-induced expression of Brain-Derived Neurotrophic Factor is disrupted in the brainstem of mecp2 null mice

    PubMed Central

    Vermehren-Schmaedick, Anke; Jenkins, Victoria K.; Knopp, Sharon J.; Balkowiec, Agnieszka; Bissonnette, John M.

    2012-01-01

    Rett syndrome is a neurodevelopmental disorder caused by loss of function mutations in the gene encoding the transcription factor methyl-CpG-binding protein 2 (MeCP2). One of its targets is the gene encoding brain-derived neurotrophic factor (bdnf). In vitro studies using cultured neurons have produced conflicting results with respect to the role of MeCP2 in BDNF expression. Acute intermittent hypoxia (AIH) induces plasticity in the respiratory system characterized by long-term facilitation of phrenic nerve amplitude. This paradigm induces an increase in BDNF protein. We hypothesized that AIH leads to augmentation of BDNF transcription in respiratory-related areas of the brainstem and that MeCP2 is necessary for this process. Wild-type and mecp2 null (mecp2−/y) mice were subjected to three 5-min episodes of exposure to 8% O2/4% CO2/88% N2, delivered at 5-min intervals. Normoxia control wild-type and mecp2 null mice were exposed to room air for the total length of time, i.e. 30 min. Following a recovery in room air, the pons and medulla were rapidly removed. Expression of BDNF protein and transcripts were determined by ELISA and quantitative PCR, respectively. AIH induced a significant increase in BDNF protein in the pons and medulla, and in mRNA transcript levels in the pons of wild-type animals. In contrast, there were no significant changes in either BDNF protein or transcripts in the pons or medulla of mice lacking Mecp2. The results indicate that Mecp2 is required for regulation of BDNF expression by acute intermittent hypoxia in vivo. PMID:22297041

  10. Ventilating patients with acute severe asthma: what do we really know?

    PubMed

    Burns, Suzanne M

    2006-01-01

    The goal of mechanical ventilation for patients with acute severe asthma is to ensure adequate oxygenation, ventilation, and gas exchange while simultaneously preventing hyperinflation, auto-positive end expiratory pressure, and subsequent barotrauma. Though existing evidence on the topic is relatively scarce, the application of current knowledge may guide our practice and prevent iatrogenic complications. To that end, this article describes selected ventilatory management strategies for the patient with acute severe asthma, such as the limitation of tidal volume size and respiratory rate, selection of specific inspiratory and expiratory ratios, the use of positive end expiratory pressure, and the application of helium-oxygen mixtures. PMID:16767021

  11. Superoxide scavengers augment contractile but not energetic responses to hypoxia in rat diaphragm.

    PubMed

    Wright, V P; Klawitter, P F; Iscru, D F; Merola, A J; Clanton, T L

    2005-05-01

    Acute exposure to severe hypoxia depresses contractile function and induces adaptations in skeletal muscle that are only partially understood. Previous studies have demonstrated that antioxidants (AOXs) given during hypoxia partially protect contractile function, but this has not been a universal finding. This study confirms that specific AOXs, known to act primarily as superoxide scavengers, protect contractile function in severe hypoxia. Furthermore, the hypothesis is tested that the mechanism of protection involves preservation of high-energy phosphates (ATP, creatine phosphate) and reductions of P(i). Rat diaphragm muscle strips were treated with AOXs and subjected to 30 min of hypoxia. Contractile function was examined by using twitch and tetanic stimulations and the degree of elevation in passive force occurring during hypoxia (contracture). High-energy phosphates were measured at the end of 30-min hypoxia exposure. Treatment with the superoxide scavengers 4,5-dihydroxy-1,3-benzenedisulfonic acid (Tiron, 10 mM) or Mn(III)tetrakis(1-methyl-4-pyridyl) porphyrin pentachloride (50 microM) suppressed contracture during hypoxia and protected maximum tetanic force. N-acetylcysteine (10 or 18 mM) had no influence on tetanic force production. Contracture during hypoxia without AOXs was also shown to be dependent on the extracellular Ca(2+) concentration. Although hypoxia resulted in only small reductions in ATP concentration, creatine phosphate concentration was decreased to approximately 10% of control. There were no consistent influences of the AOX treatments on high-energy phosphates during hypoxia. The results demonstrate that superoxide scavengers can protect contractile function and reduce contracture in hypoxia through a mechanism that does not involve preservation of high-energy phosphates. PMID:15640388

  12. [Refractory hypoxia].

    PubMed

    Cuchard, P; Guillemin, P

    2011-04-27

    We report a case of refractory hypoxia in an 85 years old smoker patient, who is known for cardiac and pulmonary comorbidities. The whole clinical picture at the time of his admission to hospital was pointing to a cardiac failure or a pneumonia that were causing the respiratory insufficiency. Despite an optimal treatment which stabilised these conditions, the patient remained severely hypoxic, but with relatively few symptoms. The non response to the oxygen and the worsening of the oxygen saturation when changing from the lying to the sitting (or supine) position finally evoke the syndrome of platypnea-orthodeoxia caused by a cardiac right to left shunt; that diagnosis was confirmed by a cardiac ultrasound with contrast which revealed an important inter-auricular shunt. The patient didn't wish to undertake the curative treatment (shunt closure). PMID:21526473

  13. A Study of Oxidative Stress Biomarkers and Effect of Oral Antioxidant Supplementation in Severe Acute Malnutrition

    PubMed Central

    Ghone, Rahul A.; Suryakar, Adinath N.; Kulhalli, P. M.; Bhagat, Sonali S.; Padalkar, Ramchandra K.; Karnik, Aarti C.; Hundekar, Prakash S.; Sangle, D. A.

    2013-01-01

    Background: Malnutrition represents one of the most severe health problems in India. Free radicals play an important role in immunological response, which induces the oxidative surplus in severe acute malnutrition. Severe dietary deficiency of nutrients leads to increased oxidative stress in cellular compartments. Aim: The goal of this study was to inspect impact of oxidative stress in the form of serum malondialdehyde as product of lipid peroxidation, vitamin E, zinc and erythrocyte superoxide dismutase in patients with severe acute malnutrition. Material and Methods: Sixty severe acute malnutrition patients were studied before and after supplementation of antioxidants for one month, and their status were compared with those of 60 age and sex matched healthy controls. The level of serum MDA was analyzed by the Kei Satoh method, serum vitamin E concentration was measured by Baker and Frank Method, serum zinc was measured by using Atomic Absorption Spectrophotometer (AAS) and erythrocyte superoxide dismutase was measured by Kajari Das Method. Results: Significantly increased levels of serum malondialdehyde (p<0.001) were found in the patients as compared to those in controls, and significant depletions were found in the levels of serum vitamin E, zinc and erythrocyte superoxide dismutase in patients with severe acute malnutrition as compared to those in controls. After supplementation of antioxidants for one month, the levels of malondialdehyde were found to be decreased significantly (p<0.001) and zinc and erythrocyte superoxide dismutase capacity levels were increased significantly (p<0.05). Also, there was a non–significant (p>0.05) increase in vitamin E levels as compared to those before supplementation results. Conclusion: Harsh deficiency of various nutrients in severe acute malnutrition leads to generation of heavy oxidative stress. These effects may be minimized with supplementation of antioxidants. PMID:24298460

  14. Valproic Acid-Induced Severe Acute Pancreatitis with Pseudocyst Formation: Report of a Case.

    PubMed

    Ray, Sukanta; Khamrui, Sujan; Kataria, Mohnish; Biswas, Jayanta; Saha, Suman

    2015-08-01

    Valproic acid is the most widely used anti-epilep-tic drug in children, and it is probably the most frequent cause of drug-induced acute pancreatitis. Outcomes for patients with valproic acid-associated pancreatitis vary from full recovery after discontinuation of the drug to severe acute pancreatitis and death. Here, we present a case of valproic acid-induced severe acute pancreatitis with pseudocyst formation in a 10-year-old girl with cerebral palsy and generalized tonic-clonic seizure. There was no resolution of the pseudocyst after discontinuation of valproic acid. The patient became symptomatic with a progressive increase in the size of the pseudocyst. She was successfully treated with cystogastrostomy and was well at 12-month follow-up. PMID:26366333

  15. Valproic Acid-Induced Severe Acute Pancreatitis with Pseudocyst Formation: Report of a Case

    PubMed Central

    Khamrui, Sujan; Kataria, Mohnish; Biswas, Jayanta; Saha, Suman

    2015-01-01

    Valproic acid is the most widely used anti-epilep­tic drug in children, and it is probably the most frequent cause of drug-induced acute pancreatitis. Outcomes for patients with valproic acid-associated pancreatitis vary from full recovery after discontinuation of the drug to severe acute pancreatitis and death. Here, we present a case of valproic acid-induced severe acute pancreatitis with pseudocyst formation in a 10-year-old girl with cerebral palsy and generalized tonic-clonic seizure. There was no resolution of the pseudocyst after discontinuation of valproic acid. The patient became symptomatic with a progressive increase in the size of the pseudocyst. She was successfully treated with cystogastrostomy and was well at 12-month follow-up. PMID:26366333

  16. Measurement of the acute metabolic response to hypoxia in rat tumours in vivo using magnetic resonance spectroscopy and hyperpolarised pyruvate

    PubMed Central

    Bluff, Joanne E.; Reynolds, Steven; Metcalf, Stephen; Alizadeh, Tooba; Kazan, Samira M.; Bucur, Adriana; Wholey, Emily G.; Bibby, Becky A.S.; Williams, Leigh; Paley, Martyn N.; Tozer, Gillian M.

    2015-01-01

    Purpose To estimate the rate constant for pyruvate to lactate conversion in tumours in response to a hypoxic challenge, using hyperpolarised 13C1-pyruvate and magnetic resonance spectroscopy. Methods and materials Hypoxic inspired gas was used to manipulate rat P22 fibrosarcoma oxygen tension (pO2), confirmed by luminescence decay of oxygen-sensitive probes. Hyperpolarised 13C1-pyruvate was injected into the femoral vein of anaesthetised rats and slice-localised 13C magnetic resonance (MR) spectra acquired. Spectral integral versus time curves for pyruvate and lactate were fitted to a precursor-product model to estimate the rate constant for tumour conversion of pyruvate to lactate (kpl). Mean arterial blood pressure (MABP) and oxygen tension (ArtpO2) were monitored. Pyruvate and lactate concentrations were measured in freeze-clamped tumours. Results MABP, ArtpO2 and tumour pO2 decreased significantly during hypoxia. kpl increased significantly (p < 0.01) from 0.029 ± 0.002 s−1 to 0.049 ± 0.006 s−1 (mean ± SEM) when animals breathing air were switched to hypoxic conditions, whereas pyruvate and lactate concentrations were minimally affected by hypoxia. Both ArtpO2 and MABP influenced the estimate of kpl, with a strong negative correlation between kpl and the product of ArtpO2 and MABP under hypoxia. Conclusion The rate constant for pyruvate to lactate conversion, kpl, responds significantly to a rapid reduction in tumour oxygenation. PMID:25824978

  17. A randomised, double blind, multicentre trial of octreotide in moderate to severe acute pancreatitis

    PubMed Central

    Uhl, W; Buchler, M; Malfertheiner, P; Beger, H; Adler, G; Gaus, W; the, G

    1999-01-01

    BACKGROUND—The pharmacological inhibition of exocrine pancreatic secretion with the somatostatin analogue octreotide has been advocated as a specific treatment of acute pancreatitis.
AIM—To investigate the efficacy of octreotide in acute pancreatitis in a randomised, placebo controlled trial.
METHODS—302 patients from 32 hospitals, fulfilling the criteria for moderate to severe acute pancreatitis within 96 hours of the onset of symptoms, were randomly assigned to one of three treatment groups: group P (n=103) received placebo, while groups O1 (n=98) and O2 (n=101) received 100 and 200 µg of octreotide, respectively, by subcutaneous injection three times daily for seven days. The primary outcome variable was a score composed of mortality and 15 typical complications of acute pancreatitis.
RESULTS—The three groups were well matched with respect to pretreatment characteristics. An intent to treat analysis of all 302 patients revealed no significant differences among treatment groups with respect to mortality (P: 16%; O1: 15%; O2: 12%), the rate of newly developed complications, the duration of pain, surgical interventions, or the length of the hospital stay. A valid for efficacy analysis (251 patients) also revealed no significant differences.
CONCLUSIONS—This trial shows no benefit of octreotide in the treatment of acute pancreatitis.


Keywords: acute pancreatitis; somatostatin; octreotide; randomised controlled multicentre trial PMID:10369711

  18. Exploring the Roles and Nature of Science: A Case Study of Severe Acute Respiratory Syndrome

    ERIC Educational Resources Information Center

    Lee, Yeung Chung

    2008-01-01

    The roles of science in society and the nature of science are the focus of many science curricula. Current views about these two aspects of science have largely been informed by the history of scientific development. This article uses the outbreak of severe acute respiratory syndrome--a recent health scare--as a case study to explore the roles of…

  19. Severe Acute Respiratory Syndrome Epidemic and Change of People's Health Behavior in China

    ERIC Educational Resources Information Center

    Tan, Xiaodong; Li, Shiyue; Wang, Chunhong; Chen, Xiaoqing; Wu, Xiaomin

    2004-01-01

    Severe Acute Respiratory Syndrome (SARS) has become a new worldwide epidemic whose origin was until recently unknown. It is the unpredictable nature of this epidemic that makes people want answers to some important questions about what they can do to protect themselves. This study presents an inquiry into peoples knowledge and self-reported…

  20. Gut DNA viromes of Malawian twins discordant for severe acute malnutrition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The bacterial component of the human gut microbiota undergoes a definable program of postnatal development. Evidence is accumulating that this program is disrupted in children with severe acute malnutrition (SAM) and that their persistent gut microbiota immaturity, which is not durably repaired with...

  1. Fear of Severe Acute Respiratory Syndrome (SARS) among Health Care Workers

    ERIC Educational Resources Information Center

    Ho, Samuel M. Y.; Kwong-Lo, Rosalie S. Y.; Mak, Christine W. Y.; Wong, Joe S.

    2005-01-01

    In this study, the authors examined fear related to severe acute respiratory syndrome (SARS) among 2 samples of hospital staff in Hong Kong. Sample 1 included health care workers (n = 82) and was assessed during the peak of the SARS epidemic. Sample 2 included hospital staff who recovered from SARS (n = 97). The results show that participants in…

  2. Management of severe acute malnutrition in low-income and middle-income countries

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Kwashiorkor and marasmus, collectively termed severe acute malnutrition (SAM), account for at least 10% of all deaths among children under 5 years of age worldwide, virtually all of them in low-income and middle-income countries. A number of risk factors, including seasonal food insecurity, environm...

  3. The utility of acoustic radiation force impulse imaging in diagnosing acute appendicitis and staging its severity

    PubMed Central

    Göya, Cemil; Hamidi, Cihad; Okur, Mehmet Hanifi; İçer, Mustafa; Oğuz, Abdullah; Hattapoğlu, Salih; Çetinçakmak, Mehmet Güli; Teke, Memik

    2014-01-01

    PURPOSE The aim of this study was to investigate the feasibility of using acoustic radiation force impulse (ARFI) imaging to diagnose acute appendicitis. METHODS Abdominal ultrasonography (US) and ARFI imaging were performed in 53 patients that presented with right lower quadrant pain, and the results were compared with those obtained in 52 healthy subjects. Qualitative evaluation of the patients was conducted by Virtual Touch™ tissue imaging (VTI), while quantitative evaluation was performed by Virtual Touch™ tissue quantification (VTQ) measuring the shear wave velocity (SWV). The severity of appendix inflammation was observed and rated using ARFI imaging in patients diagnosed with acute appendicitis. Alvarado scores were determined for all patients presenting with right lower quadrant pain. All patients diagnosed with appendicitis received appendectomies. The sensitivity and specificity of ARFI imaging relative to US was determined upon confirming the diagnosis of acute appendicitis via histopathological analysis. RESULTS The Alvarado score had a sensitivity and specificity of 70.8% and 20%, respectively, in detecting acute appendicitis. Abdominal US had 83.3% sensitivity and 80% specificity, while ARFI imaging had 100% sensitivity and 98% specificity, in diagnosing acute appendicitis. The median SWV value was 1.11 m/s (range, 0.6–1.56 m/s) for healthy appendix and 3.07 m/s (range, 1.37–4.78 m/s) for acute appendicitis. CONCLUSION ARFI imaging may be useful in guiding the clinical management of acute appendicitis, by helping its diagnosis and determining the severity of appendix inflammation. PMID:25323836

  4. In Vivo Imaging of Retinal Hypoxia in a Model of Oxygen-Induced Retinopathy

    PubMed Central

    Uddin, Md. Imam; Evans, Stephanie M.; Craft, Jason R.; Capozzi, Megan E.; McCollum, Gary W.; Yang, Rong; Marnett, Lawrence J.; Uddin, Md. Jashim; Jayagopal, Ashwath; Penn, John S.

    2016-01-01

    Ischemia-induced hypoxia elicits retinal neovascularization and is a major component of several blinding retinopathies such as retinopathy of prematurity (ROP), diabetic retinopathy (DR) and retinal vein occlusion (RVO). Currently, noninvasive imaging techniques capable of detecting and monitoring retinal hypoxia in living systems do not exist. Such techniques would greatly clarify the role of hypoxia in experimental and human retinal neovascular pathogenesis. In this study, we developed and characterized HYPOX-4, a fluorescence-imaging probe capable of detecting retinal-hypoxia in living animals. HYPOX-4 dependent in vivo and ex vivo imaging of hypoxia was tested in a mouse model of oxygen-induced retinopathy (OIR). Predicted patterns of retinal hypoxia were imaged by HYPOX-4 dependent fluorescence activity in this animal model. In retinal cells and mouse retinal tissue, pimonidazole-adduct immunostaining confirmed the hypoxia selectivity of HYPOX-4. HYPOX-4 had no effect on retinal cell proliferation as indicated by BrdU assay and exhibited no acute toxicity in retinal tissue as indicated by TUNEL assay and electroretinography (ERG) analysis. Therefore, HYPOX-4 could potentially serve as the basis for in vivo fluorescence-based hypoxia-imaging techniques, providing a tool for investigators to understand the pathogenesis of ischemic retinopathies and for physicians to address unmet clinical needs. PMID:27491345

  5. In Vivo Imaging of Retinal Hypoxia in a Model of Oxygen-Induced Retinopathy.

    PubMed

    Uddin, Md Imam; Evans, Stephanie M; Craft, Jason R; Capozzi, Megan E; McCollum, Gary W; Yang, Rong; Marnett, Lawrence J; Uddin, Md Jashim; Jayagopal, Ashwath; Penn, John S

    2016-01-01

    Ischemia-induced hypoxia elicits retinal neovascularization and is a major component of several blinding retinopathies such as retinopathy of prematurity (ROP), diabetic retinopathy (DR) and retinal vein occlusion (RVO). Currently, noninvasive imaging techniques capable of detecting and monitoring retinal hypoxia in living systems do not exist. Such techniques would greatly clarify the role of hypoxia in experimental and human retinal neovascular pathogenesis. In this study, we developed and characterized HYPOX-4, a fluorescence-imaging probe capable of detecting retinal-hypoxia in living animals. HYPOX-4 dependent in vivo and ex vivo imaging of hypoxia was tested in a mouse model of oxygen-induced retinopathy (OIR). Predicted patterns of retinal hypoxia were imaged by HYPOX-4 dependent fluorescence activity in this animal model. In retinal cells and mouse retinal tissue, pimonidazole-adduct immunostaining confirmed the hypoxia selectivity of HYPOX-4. HYPOX-4 had no effect on retinal cell proliferation as indicated by BrdU assay and exhibited no acute toxicity in retinal tissue as indicated by TUNEL assay and electroretinography (ERG) analysis. Therefore, HYPOX-4 could potentially serve as the basis for in vivo fluorescence-based hypoxia-imaging techniques, providing a tool for investigators to understand the pathogenesis of ischemic retinopathies and for physicians to address unmet clinical needs. PMID:27491345

  6. Acute liver injury with severe coagulopathy in marasmus caused by a somatic delusional disorder.

    PubMed

    Stein, Lance L; Jesudian, Arun B

    2011-01-01

    Marasmus is a severe form of protein-calorie malnutrition characterized by the depletion of fat stores, muscle wasting, and the lack of edema. In developed countries, marasmus is often the result of anorexia nervosa. Abnormal transaminases with liver synthetic dysfunction have rarely been reported with anorexia nervosa. To our knowledge, we report the first detailed case of acute liver injury with severe coagulopathy (INR > 1.5) in a patient with marasmus due to self-induced calorie restriction caused by a somatic delusional disorder. This case highlights the severity of liver injury that may occur with significant weight loss from self-induced calorie restriction and the rapid normalization of this injury with treatment. It is important for clinicians to be aware of patterns of acute liver injury in patients with severe protein-calorie malnutrition, regardless of the underlying cause. PMID:25954537

  7. A case of severe thrombocytopaenia associated with acute HIV-1 infection.

    PubMed

    Aoki, Ami; Moro, Hiroshi; Watanabe, Takayuki; Asakawa, Katsuaki; Miura, Satoru; Moriyama, Masato; Tanabe, Yoshinari; Kagamu, Hiroshi; Narita, Ichiei

    2015-03-01

    A 23-year-old man was admitted to our hospital with severe thrombocytopaenia. He had unprotected sexual contact 6 weeks earlier. He was diagnosed with acute HIV infection by means of HIV RNA viral load testing and HIV-associated thrombocytopaenia. Although his thrombocytopaenia improved immediately with short-term dexamethasone therapy, this effect was not sustained after cessation of therapy. Antiretroviral therapy including raltegravir was initiated, and the patient recovered from severe thrombocytopaenia within several days. The findings from this case suggest that acute HIV infection should be suspected with unexplained thrombocytopaenia, and that antiretroviral therapy is the treatment of choice for severe HIV-associated thrombocytopaenia, even when in the early period following acquisition of the virus. PMID:24737880

  8. Association of Interleukin-8 and Neutrophils with Nasal Symptom Severity During Acute Respiratory Infection

    PubMed Central

    Henriquez, Kelsey M.; Hayney, Mary S.; Xie, Yaoguo; Zhang, Zhengjun; Barrett, Bruce

    2015-01-01

    Using a large data set (n = 811), the relationship between acute respiratory infection illness severity and inflammatory biomarkers was investigated to determine whether certain symptoms are correlated more closely than others with the inflammatory biomarkers, interleukin-8 (IL-8) and nasal neutrophils. Participants with community acquired acute respiratory infection underwent nasal lavage for IL-8 and neutrophil testing, in addition to multiplex polymerase chain reaction (PCR) methods for the detection and identification of respiratory viruses. Information about symptoms was obtained throughout the duration of the illness episode using the well-validated Wisconsin Upper Respiratory Symptom Survey (WURSS-21). Global symptom severity was calculated by the area under the curve (AUC) plotting duration versus WURSS total. Of the specimens tested, 56% were positively identified for one or more of nine different respiratory viruses. During acute respiratory infection illness, both IL-8 and neutrophils positively correlate with AUC (rs = 0.082, P = 0.022; rs = 0.080, P = 0.030). IL-8 and neutrophils correlate with nasal symptom severity: runny nose (r = 0.13, P = <0.00001; r = 0.18, P = <0.003), plugged nose (r = 0.045, P = 0.003; r = 0.14, P = 0.058), and sneezing (r = −0.02, P = <0.0001; r = −0.0055, P = 0.31). Neutrophils correlate with some quality of life measures such as sleeping well (r = 0.15, P = 0.026). Thus, the study demonstrates that IL-8 and neutrophils are correlated with severity of nasal symptoms during acute respiratory infection. Further research is necessary to determine if the concentration of these or other biomarkers can predict the overall duration and severity of acute respiratory infection illness. PMID:25132248

  9. The economic impact of the insured patients with severe chronic and acute illnesses: a qualitative approach

    PubMed Central

    Aji, Budi; Yamamoto, Shelby Suzanne; Sauerborn, Rainer

    2014-01-01

    Background Little research has focused on the economic hardship among the insured with severe illnesses and high treatment costs, in particular, the consequence of poorer insurance coverage for high-cost illnesses. Therefore, we presented the case for identifying the experiences of insured patients with severe chronic and acute illnesses. This study identified a qualitative understanding of the economic impact of severe chronic and acute illnesses and household strategies to deal with high treatment costs. Design Interviews were conducted with 19 insured households of three different health insurance programs with a family member that had been hospitalized for severe chronic or acute illnesses in either Banyumas or Margono Sukarjo hospitals in Banyumas, Central Java, Indonesia. A thematic analysis was applied to guide the interpretation of the data. Results Insured households with a family member that had been hospitalized for severe chronic and acute illnesses were greatly affected by the high treatment costs. Four major issues emerged from this qualitative study: insured patients are still burdened with high out-of-pocket payments, households adopt various strategies to cope with the high cost of treatments, households experience financial hardships, and positive and negative perceptions of the insured regarding their health insurance coverage for acute and chronic illnesses. Conclusions Askes and Jamsostek patients faced financial burdens from high cost sharing for hospital amenities, non-covered drugs, and treatments and other indirect costs. Meanwhile, Jamkesmas beneficiaries faced no financial burden for related medical services but were rather burdened with indirect costs for the carers. Households relied on internal resources to cover hospital bills as the first strategy, which included the mobilization of savings, sale of assets, and borrowing of money. External support was tapped secondarily and included financial support from extended family members

  10. Renal developmental defects resulting from in utero hypoxia are associated with suppression of ureteric β-catenin signaling.

    PubMed

    Wilkinson, Lorine J; Neal, Cailda S; Singh, Reetu R; Sparrow, Duncan B; Kurniawan, Nyoman D; Ju, Adler; Grieve, Stuart M; Dunwoodie, Sally L; Moritz, Karen M; Little, Melissa H

    2015-05-01

    Gestational stressors, including glucocorticoids and protein restriction, can affect kidney development and hence final nephron number. Since hypoxia is a common insult during pregnancy, we studied the influence of oxygen tension on kidney development in models designed to represent a pathological hypoxic insult. In vivo mouse models of moderate, transient, midgestational (12% O₂, 48 h, 12.5 dpc) or severe, acute, early-gestational (5.5-7.5% O₂, 8 h, 9.5-10.5 dpc) hypoxia were developed. The embryo itself is known to mature under hypoxic conditions with embryonic tissue levels of oxygen estimated to be 5%-8% (physiological hypoxia) when the mother is exposed to ambient normoxia. Both in vivo models generated phenotypes seen in patients with congenital anomalies of the kidney and urinary tract (CAKUT). Severe, acute, early hypoxia resulted in duplex kidney, while moderate, transient, midgestational hypoxia permanently reduced ureteric branching and nephron formation. Both models displayed hypoxia-induced reductions in β-catenin signaling within the ureteric tree and suppression of the downstream target gene, Ccnd1. Thus, we show a link between gestational hypoxia and CAKUT, the phenotype of which varies with timing, duration, and severity of the hypoxic insult. PMID:25587709

  11. [New advance of research on therapy of severe acute radiation sickness with mesenchymal stem cells].

    PubMed

    Guo, Ling-Ling; Li, Ming; Xing, Shuang; Luo, Qing-Liang

    2011-06-01

    Mesenchymal stem cells (MSC) are a kind of non-hematopoietic adult stem cells with self-renewal and multilineage differentiation potential, which have special biological characteristics, such as secreting various cytokines, promoting hematopoiesis, accelerating stem cells homing and reconstructing hematopoietic microenvironment. MSC are collected and amplified easily, and can be transfected by exogenous gene. Many reports indicated that MSC were applied in therapy for variety of tissues and organs injury, meanwhile the treatment for acute radiation sickness has made significant progress. In this review, the biological characteristics and new research advance on MSC in treatment of severe acute radiation sickness are summarized and discussed. PMID:21729581

  12. Increased gene expression for VEGF and the VEGF receptors KDR/Flk and Flt in lungs exposed to acute or to chronic hypoxia. Modulation of gene expression by nitric oxide.

    PubMed Central

    Tuder, R M; Flook, B E; Voelkel, N F

    1995-01-01

    Endothelial cells constitute an essential integrator of factors that effect blood vessel remodeling induced by chronic hypoxia. We hypothesized that vascular endothelial growth factor (VEGF) may participate in the lung response to acute and to chronic hypoxia. We found that ex vivo perfusion of isolated lungs under hypoxic conditions (when compared with normoxia) caused an increase in lung tissue mRNA of VEGF and of the VEGF receptors KDR/Flk and Flt. Chronic hypobaric hypoxia also increased lung tissue mRNA levels of VEGF, KDR/Flk, and Flt and the amount of VEGF protein. In situ hybridization studies demonstrated increased VEGF and KDR/flk hybridization signals in lungs from chronically hypoxic rats. Since endotoxin treatment of rats decreased lung VEGF mRNA, we postulated that nitric oxide (NO) or an NO-related metabolite might be involved in lung VEGF gene expression. Indeed, sodium nitroprusside, a NO donor, decreased and L-NAME (N-nitro-L-arginine methyl ester), an inhibitor of NO-synthesis, increased both VEGF and VEGF receptor transcripts. We conclude that VEGF in the isolated perfused lung acts as an early gene in response to hypoxia and that lung VEGF and VEGF receptor mRNA levels are influenced by hypoxia and NO-dependent mechanisms. Images PMID:7706486

  13. The volatile anesthetic isoflurane differentially suppresses the induction of erythropoietin synthesis elicited by acute anemia and systemic hypoxemia in mice in an hypoxia-inducible factor-2-dependent manner.

    PubMed

    Kai, Shinichi; Tanaka, Tomoharu; Matsuyama, Tomonori; Suzuki, Kengo; Hirota, Kiichi

    2014-06-01

    Erythropoietin (EPO) is a glycoprotein hormone essential for the regulation of erythroid homeostasis. Although EPO production is prominent in the kidney and liver, its production in the central nervous system has also been detected. Tissue hypoxia due to systemic or local hypoxemia and acute anemia due to blood loss occurs frequently during various clinical settings, leading to a high possibility of elevated plasma EPO levels. However, it is largely unknown whether volatile anesthetic agents affect EPO production elicited by acute hypoxia in vivo. Male C57BL/6N CrSlc mice were exposed to a hypoxic insult as a result of bleeding-related anemia or hypoxemia while they were under anesthetized using various concentrations of isoflurane. EPO protein concentrations were assessed by enzyme-linked immunosorbent assay and mRNA levels were measured by quantitative real-time reverse transcriptase-polymerase chain reaction. Plasma EPO concentration was induced as early as 3h following acute anemic and hypoxemic hypoxia and suppressed by clinically relevant doses of isoflurane in a dose-dependent manner. Anemic hypoxia induced EPO mRNA and protein synthesis in the kidney. In the kidney, isoflurane inhibited EPO induction caused by anemia but not that caused by hypoxemia. On the other hand, in the brain hypoxemia-induced EPO production was suppressed by isoflurane. Finally, qRT-PCR studies demonstrate that isoflurane differentially inhibit HIF-1α and HIF-2α mRNA expression in brain and kidney, indicating the involvement of HIF-2 in the hypoxia-induced EPO expression and inhibition of the induction by isoflurane. PMID:24680923

  14. CT Evaluation of Acute Pancreatitis and its Prognostic Correlation with CT Severity Index

    PubMed Central

    Gupta, Rajesh; Vyas, Mahendra Mohan; Sharma, Rakesh

    2016-01-01

    Introduction Pancreatitis is one of most complex and clinically challenging of all abdominal disorders. USG and abdominal CT are the most commonly used diagnostic imaging modalities for the evaluation of pancreas. Computed Tomography (CT) is highly accurate and sensitive than USG in both diagnosing as well as demonstrating the extent. Early assessment of the cause and severity of acute pancreatitis is of utmost importance for prompt treatment and close monitoring of patient with severe disease. CT is the imaging method of choice for assessing the extent of acute pancreatitis and for evaluating complications. Aim To assess prognostic correlation and clinical outcome of acute pancreatitis on the basis of CT severity index. Materials and Methods A prospective study of 50 cases was carried out in the Department of Radio Diagnosis, with complaint suggestive of acute pancreatitis on the basis of clinical/laboratory/ultrasonography findings were evaluated in Siemens somatom 40 slice CT. The severity of pancreatitis was scored using CT severity index, modified severity index and revised Atlanta classification and classified into mild, moderate, severe categories. Clinical follow-up of the patients was done in terms of the following parameters: Length of hospital stay, Need for surgery or percutaneous intervention, Evidence of infection in any organ system, Occurrence of organ failure- respiratory, cardiovascular, renal, hepatic and haematological system, death. The clinical outcome was compared with the currently accepted Balthazar’s CTSI and Modified Mortele’s CTSI and revised Atlanta classification in all the cases. Results Gall stone disease was most common aetiological factor seen in 40% cases, it was more common in females than males. Alcohol was second most common aetiological factor seen in 38% cases and was noted only in males. Pleural effusion was the most common extra-pancreatic complication seen in 46% cases. Balthazar grade C was the most common (40

  15. Acute SGLT inhibition normalizes O2 tension in the renal cortex but causes hypoxia in the renal medulla in anaesthetized control and diabetic rats.

    PubMed

    O'Neill, Julie; Fasching, Angelica; Pihl, Liselotte; Patinha, Daniela; Franzén, Stephanie; Palm, Fredrik

    2015-08-01

    Early stage diabetic nephropathy is characterized by glomerular hyperfiltration and reduced renal tissue Po2. Recent observations have indicated that increased tubular Na(+)-glucose linked transport (SGLT) plays a role in the development of diabetes-induced hyperfiltration. The aim of the present study was to determine how inhibition of SLGT impacts upon Po2 in the diabetic rat kidney. Diabetes was induced by streptozotocin in Sprague-Dawley rats 2 wk before experimentation. Renal hemodynamics, excretory function, and renal O2 homeostasis were measured in anesthetized control and diabetic rats during baseline and after acute SGLT inhibition using phlorizin (200 mg/kg ip). Baseline arterial pressure was similar in both groups and unaffected by SGLT inhibition. Diabetic animals displayed reduced baseline Po2 in both the cortex and medulla. SGLT inhibition improved cortical Po2 in the diabetic kidney, whereas it reduced medullary Po2 in both groups. SGLT inhibition reduced Na(+) transport efficiency [tubular Na(+) transport (TNa)/renal O2 consumption (Qo2)] in the control kidney, whereas the already reduced TNa/Qo2 in the diabetic kidney was unaffected by SGLT inhibition. In conclusion, these data demonstrate that when SGLT is inhibited, renal cortex Po2 in the diabetic rat kidney is normalized, which implies that increased proximal tubule transport contributes to the development of hypoxia in the diabetic kidney. The reduction in medullary Po2 in both control and diabetic kidneys during the inhibition of proximal Na(+) reabsorption suggests the redistribution of active Na(+) transport to less efficient nephron segments, such as the medullary thick ascending limb, which results in medullary hypoxia. PMID:26041448

  16. Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment: a Delphi consensus.

    PubMed

    Schmiegelow, Kjeld; Attarbaschi, Andishe; Barzilai, Shlomit; Escherich, Gabriele; Frandsen, Thomas Leth; Halsey, Christina; Hough, Rachael; Jeha, Sima; Kato, Motohiro; Liang, Der-Cherng; Mikkelsen, Torben Stamm; Möricke, Anja; Niinimäki, Riitta; Piette, Caroline; Putti, Maria Caterina; Raetz, Elizabeth; Silverman, Lewis B; Skinner, Roderick; Tuckuviene, Ruta; van der Sluis, Inge; Zapotocka, Ester

    2016-06-01

    Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi method, 15 international childhood acute lymphoblastic leukaemia study groups assessed acute lymphoblastic leukaemia protocols to address toxic effects that were to be considered by the Ponte di Legno working group. 14 acute toxic effects (hypersensitivity to asparaginase, hyperlipidaemia, osteonecrosis, asparaginase-associated pancreatitis, arterial hypertension, posterior reversible encephalopathy syndrome, seizures, depressed level of consciousness, methotrexate-related stroke-like syndrome, peripheral neuropathy, high-dose methotrexate-related nephrotoxicity, sinusoidal obstructive syndrome, thromboembolism, and Pneumocystis jirovecii pneumonia) that are serious but too rare to be addressed comprehensively within any single group, or are deemed to need consensus definitions for reliable incidence comparisons, were selected for assessment. Our results showed that none of the protocols addressed all 14 toxic effects, that no two protocols shared identical definitions of all toxic effects, and that no toxic effect definition was shared by all protocols. Using the Delphi method over three face-to-face plenary meetings, consensus definitions were obtained for all 14 toxic effects. In the overall assessment of outcome of acute lymphoblastic leukaemia treatment, these expert opinion-based definitions will allow reliable comparisons of frequencies and severities of acute toxic effects across treatment protocols, and facilitate international research on cause, guidelines for treatment adaptation, preventive strategies, and development of consensus algorithms for reporting on acute lymphoblastic leukaemia treatment. PMID:27299279

  17. Geographic Access to High Capability Severe Acute Respiratory Failure Centers in the United States

    PubMed Central

    Wallace, David J.; Angus, Derek C.; Seymour, Christopher W.; Yealy, Donald M.; Carr, Brendan G.; Kurland, Kristen; Boujoukos, Arthur; Kahn, Jeremy M.

    2014-01-01

    Objective Optimal care of adults with severe acute respiratory failure requires specific resources and expertise. We sought to measure geographic access to these centers in the United States. Design Cross-sectional analysis of geographic access to high capability severe acute respiratory failure centers in the United States. We defined high capability centers using two criteria: (1) provision of adult extracorporeal membrane oxygenation (ECMO), based on either 2008–2013 Extracorporeal Life Support Organization reporting or provision of ECMO to 2010 Medicare beneficiaries; or (2) high annual hospital mechanical ventilation volume, based 2010 Medicare claims. Setting Nonfederal acute care hospitals in the United States. Measurements and Main Results We defined geographic access as the percentage of the state, region and national population with either direct or hospital-transferred access within one or two hours by air or ground transport. Of 4,822 acute care hospitals, 148 hospitals met our ECMO criteria and 447 hospitals met our mechanical ventilation criteria. Geographic access varied substantially across states and regions in the United States, depending on center criteria. Without interhospital transfer, an estimated 58.5% of the national adult population had geographic access to hospitals performing ECMO and 79.0% had geographic access to hospitals performing a high annual volume of mechanical ventilation. With interhospital transfer and under ideal circumstances, an estimated 96.4% of the national adult population had geographic access to hospitals performing ECMO and 98.6% had geographic access to hospitals performing a high annual volume of mechanical ventilation. However, this degree of geographic access required substantial interhospital transfer of patients, including up to two hours by air. Conclusions Geographic access to high capability severe acute respiratory failure centers varies widely across states and regions in the United States. Adequate

  18. Chronic hypoxia enhances adenosine release in rat PC12 cells by altering adenosine metabolism and membrane transport.

    PubMed

    Kobayashi, S; Zimmermann, H; Millhorn, D E

    2000-02-01

    Acute exposure to hypoxia causes a release of adenosine (ADO) that is inversely related to the O2 levels in oxygen-sensitive pheochromocytoma (PC12) cells. In the current study, chronic exposure (48 h) of PC12 cells to moderate hypoxia (5% O2) significantly enhanced the release of ADO during severe, acute hypoxia (1% O2). Investigation into the intra- and extracellular mechanisms underpinning the secretion of ADO in PC12 cells chronically exposed to hypoxia revealed changes in gene expression and activities of several key enzymes associated with ADO production and metabolism, as well as the down-regulation of a nucleoside transporter. Decreases in the enzymatic activities of ADO kinase and ADO deaminase accompanied by an increase in those of cytoplasmic and ecto-5'-nucleotidases bring about an increased capacity to produce intra- and extracellular ADO. This increased potential to generate ADO and decreased capacity to metabolize ADO indicate that PC12 cells shift toward an ADO producer phenotype during hypoxia. The reduced function of the rat equilibrative nucleoside transporter rENT1 also plays a role in controlling extracellular ADO levels. The hypoxia-induced alterations in the ADO metabolic enzymes and the rENT1 transporter seem to increase the extracellular concentration of ADO. The biological significance of this regulation is unclear but is likely to be associated with modulating cellular activity during hypoxia. PMID:10646513

  19. Cross-host evolution of severe acute respiratory syndrome coronavirus in palm civet and human

    PubMed Central

    Song, Huai-Dong; Tu, Chang-Chun; Zhang, Guo-Wei; Wang, Sheng-Yue; Zheng, Kui; Lei, Lian-Cheng; Chen, Qiu-Xia; Gao, Yu-Wei; Zhou, Hui-Qiong; Xiang, Hua; Zheng, Hua-Jun; Chern, Shur-Wern Wang; Cheng, Feng; Pan, Chun-Ming; Xuan, Hua; Chen, Sai-Juan; Luo, Hui-Ming; Zhou, Duan-Hua; Liu, Yu-Fei; He, Jian-Feng; Qin, Peng-Zhe; Li, Ling-Hui; Ren, Yu-Qi; Liang, Wen-Jia; Yu, Ye-Dong; Anderson, Larry; Wang, Ming; Xu, Rui-Heng; Wu, Xin-Wei; Zheng, Huan-Ying; Chen, Jin-Ding; Liang, Guodong; Gao, Yang; Liao, Ming; Fang, Ling; Jiang, Li-Yun; Li, Hui; Chen, Fang; Di, Biao; He, Li-Juan; Lin, Jin-Yan; Tong, Suxiang; Kong, Xiangang; Du, Lin; Hao, Pei; Tang, Hua; Bernini, Andrea; Yu, Xiao-Jing; Spiga, Ottavia; Guo, Zong-Ming; Pan, Hai-Yan; He, Wei-Zhong; Manuguerra, Jean-Claude; Fontanet, Arnaud; Danchin, Antoine; Niccolai, Neri; Li, Yi-Xue; Wu, Chung-I; Zhao, Guo-Ping

    2005-01-01

    The genomic sequences of severe acute respiratory syndrome coronaviruses from human and palm civet of the 2003/2004 outbreak in the city of Guangzhou, China, were nearly identical. Phylogenetic analysis suggested an independent viral invasion from animal to human in this new episode. Combining all existing data but excluding singletons, we identified 202 single-nucleotide variations. Among them, 17 are polymorphic in palm civets only. The ratio of nonsynonymous/synonymous nucleotide substitution in palm civets collected 1 yr apart from different geographic locations is very high, suggesting a rapid evolving process of viral proteins in civet as well, much like their adaptation in the human host in the early 2002–2003 epidemic. Major genetic variations in some critical genes, particularly the Spike gene, seemed essential for the transition from animal-to-human transmission to human-to-human transmission, which eventually caused the first severe acute respiratory syndrome outbreak of 2002/2003. PMID:15695582

  20. What factors determine the severity of hepatitis A-related acute liver failure?

    PubMed Central

    Ajmera, V.; Xia, G.; Vaughan, G.; Forbi, J. C.; Ganova-Raeva, L. M.; Khudyakov, Y.; Opio, C. K.; Taylor, R.; Restrepo, R.; Munoz, S.; Fontana, R. J.; Lee, W. M.

    2016-01-01

    SUMMARY The reason(s) that hepatitis A virus (HAV) infection may progress infrequently to acute liver failure are poorly understood. We examined host and viral factors in 29 consecutive adult patients with HAV-associated acute liver failure enrolled at 10 sites participating in the US ALF Study Group. Eighteen of twenty-four acute liver failure sera were PCR positive while six had no detectable virus. HAV genotype was determined using phylogenetic analysis and the full-length genome sequences of the HAV from a cute liver failure sera were compared to those from self-limited acute HAV cases selected from the CDC database. We found that rates of nucleotide substitution did not vary significantly between the liver failure and non-liver failure cases and there was no significant variation in amino acid sequences between the two groups. Four of 18 HAV isolates were subgenotype IB, acquired from the same study site over a 3.5-year period. Sub-genotype IB was found more frequently among acute liver failure cases compared to the non-liver failure cases (chi-square test, P < 0.01). At another centre, a mother and her son presented with HAV and liver failure within 1 month of each other. Predictors of spontaneous survival included detectable serum HAV RNA, while age, gender, HAV genotype and nucleotide substitutions were not associated with outcome. The more frequent appearance of rapid viral clearance and its association with poor outcomes in acute liver failure as well as the finding of familial cases imply a possible host genetic predisposition that contributes to a fulminant course. Recurrent cases of the rare subgenotype IB over several years at a single centre imply a community reservoir of infection and possible increased pathogenicity of certain infrequent viral genotypes. PMID:21143345

  1. Acute Radiation Syndrome Severity Score System in Mouse Total-Body Irradiation Model.

    PubMed

    Ossetrova, Natalia I; Ney, Patrick H; Condliffe, Donald P; Krasnopolsky, Katya; Hieber, Kevin P

    2016-08-01

    Radiation accidents or terrorist attacks can result in serious consequences for the civilian population and for military personnel responding to such emergencies. The early medical management situation requires quantitative indications for early initiation of cytokine therapy in individuals exposed to life-threatening radiation doses and effective triage tools for first responders in mass-casualty radiological incidents. Previously established animal (Mus musculus, Macaca mulatta) total-body irradiation (γ-exposure) models have evaluated a panel of radiation-responsive proteins that, together with peripheral blood cell counts, create a multiparametic dose-predictive algorithm with a threshold for detection of ~1 Gy from 1 to 7 d after exposure as well as demonstrate the acute radiation syndrome severity score systems created similar to the Medical Treatment Protocols for Radiation Accident Victims developed by Fliedner and colleagues. The authors present a further demonstration of the acute radiation sickness severity score system in a mouse (CD2F1, males) TBI model (1-14 Gy, Co γ-rays at 0.6 Gy min) based on multiple biodosimetric endpoints. This includes the acute radiation sickness severity Observational Grading System, survival rate, weight changes, temperature, peripheral blood cell counts and radiation-responsive protein expression profile: Flt-3 ligand, interleukin 6, granulocyte-colony stimulating factor, thrombopoietin, erythropoietin, and serum amyloid A. Results show that use of the multiple-parameter severity score system facilitates identification of animals requiring enhanced monitoring after irradiation and that proteomics are a complementary approach to conventional biodosimetry for early assessment of radiation exposure, enhancing accuracy and discrimination index for acute radiation sickness response categories and early prediction of outcome. PMID:27356057

  2. A case of severe acute pancreatitis treated with CTR-001 direct hemoperfusion for cytokine apheresis.

    PubMed

    Saotome, Takao; Endo, Yoshihiro; Sasaki, Teiji; Tabata, Takahisa; Hamamoto, Tetsu; Fujino, Kazunori; Andoh, Akira; Eguchi, Yutaka; Tani, Tohru; Fujiyama, Yoshihide

    2005-08-01

    Severe acute pancreatitis is a clinical entity that can develop into multiple organ failure (MOF), and still has a poor prognosis. It is generally agreed that excessive humoral mediators such as pro-inflammatory cytokines play important roles in the pathogenesis of organ failure in patients with severe acute pancreatitis (SAP). Furthermore, it has been reported that continuous hemodiafiltration (CHDF) can remove the excess humoral mediators during the hypercytokinemic state of systemic inflammatory response syndrome (SIRS). We experienced a case of severe acute pancreatitis induced by alcohol abuse, on whom we performed cytokine apheresis. The patient was a 46 year-old male. He received 14 cytokine apheresis procedures, for about 4 hours in each session, using a CTR-001 direct hemoperfusion (DHP) cartridge. His serum levels of pro-inflammatory cytokines such as interleukin-6 (IL-6; 1649.1+/-667.1-1257.1+/-489.4 pg/mL, P=0.013) decreased significantly after the CTR-001 procedures. However tumor necrosis factor-alpha (TNF-alpha) (26.2+/-1.7-24.3+/-1.9 pg/mL, P=0.087), IL-1beta (6.1+/-2.9-3.49+/-1.1 pg/mL, P=0.477), IL-8 (192.5+/-33.4-229.5+/-51.8 pg/mL, P=0.754) and IL-10 (14.4+/-2.7-14.0+/-1.9 pg/mL, P=0.726) did not decrease statistically. Therefore, we conclude that in this case, cytokine apheresis using a CTR-001 cartridge was effective for reducing the pro-inflammatory cytokines during severe acute pancreatitis. PMID:16076384

  3. Platelet-rich plasma (PRP) treatment of sports-related severe acute hamstring injuries

    PubMed Central

    Guillodo, Yannick; Madouas, Gwénaelle; Simon, Thomas; Le Dauphin, Hermine; Saraux, Alain

    2015-01-01

    Summary Purpose hamstring injury is the most common musculoskeletal disorder and one of the main causes of missed sporting events. Shortening the time to return to play (TTRTP) is a priority for athletes and sports medicine practitioners. Hypothesis platelet-rich plasma (PRP) injection at the site of severe acute hamstring injury increases the healing rate and shortens the TTRTP. Study design Cohort study. Methods all patients with ultrasonography and MRI evidence of severe acute hamstring injury between January 2012 and March 2014 were offered PRP treatment. Those who accepted received a single intramuscular PRP injection within 8 days post-injury; the other patients served as controls. The same standardized rehabilitation program was used in both groups. A physical examination and ultrasonography were performed 10 and 30 days post-injury, then a phone interview 120 days post-injury, to determine the TTRTP at the pre-injury level. Results of 34 patients, 15 received PRP and 19 did not. Mean TTRTP at the pre-injury level was 50.9±10.7 days in the PRP group and 52.8±15.7 days in the control group. The difference was not statistically significant. Conclusion a single intramuscular PRP injection did not shorten the TTRTP in sports people with severe acute hamstring injuries. PMID:26958537

  4. Sex-specific effects of N-acetylcysteine in neonatal rats treated with hypothermia after severe hypoxia-ischemia.

    PubMed

    Nie, Xingju; Lowe, Danielle W; Rollins, Laura Grace; Bentzley, Jessica; Fraser, Jamie L; Martin, Renee; Singh, Inderjit; Jenkins, Dorothea

    2016-07-01

    Approximately half of moderate to severely hypoxic-ischemic (HI) newborns do not respond to hypothermia, the only proven neuroprotective treatment. N-acetylcysteine (NAC), an antioxidant and glutathione precursor, shows promise for neuroprotection in combination with hypothermia, mitigating post-HI neuroinflammation due to oxidative stress. As mechanisms of HI injury and cell death differ in males and females, sex differences must be considered in translational research of neuroprotection. We assessed the potential toxicity and efficacy of NAC in combination with hypothermia, in male and female neonatal rats after severe HI injury. NAC 50mg/kg/d administered 1h after initiation of hypothermia significantly decreased iNOS expression and caspase 3 activation in the injured hemisphere versus hypothermia alone. However, only females treated with hypothermia +NAC 50mg/kg showed improvement in short-term infarct volumes compared with saline treated animals. Hypothermia alone had no effect in this severe model. When NAC was continued for 6 weeks, significant improvement in long-term neuromotor outcomes over hypothermia treatment alone was observed, controlling for sex. Antioxidants may provide insufficient neuroprotection after HI for neonatal males in the short term, while long-term therapy may benefit both sexes. PMID:26851769

  5. [Current approaches to the treatment of severe hypoxic respiratory insufficiency (acute lung injury; acute respiratory distress syndrome)].

    PubMed

    Kluge, S; Müller, T; Pfeifer, M

    2011-02-01

    Lung-protective ventilation with a low tidal volume, plateau pressure < 30 cm H(2)O. oxygen saturation > 90% and permissive hypercapnia results in reduction of the mortality rate in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). The level of the positive end-expiratory pressure (PEEP) must be chosen in relation to oxygen requirement. High frequency oscillatory ventilation and neurally adjusted ventilatory assist are promising methods. However, further studies with firm end-points have to be awaited before a final judgment is possible. Veno-venous extracorporeal membrane oxygenation (ECMO) can ensure life-sustaining gas exchange in patients with severe vitally compromised pulmonary failure, to provide time for lung tissue to heal and reduce ventilatory stress. The latest guidelines for analgesia and sedation in intensive care medicine demand consistent monitoring of the level of sedation and the intensity of pain. The sedation should be interrupted daily, with phases of awakenings and, if possible, spontaneous breathing. Methods of supportive treatment: Positional treatment (prone position) and inhalation of vasodilators can improve ventilation/perfusion mismatch and thus oxygenation. However, administration of surfactant is currently not advised in adult respiratory failure. PMID:21271478

  6. [Severe pulmonary embolism and acute lower limb ischemia complicating peripartum cardiomyopathy successfully treated by streptokinase].

    PubMed

    Yaméogo, N V; Kaboré, E; Seghda, A; Kagambèga, L J; Kaboré, H P; Millogo, G R C; Kologo, K J; Kambiré, Y; Bama, A; Toguyeni, B J Y; Samadoulougou, A K; Zabsonré, P

    2016-02-01

    Peripartum cardiomyopathy is a cardiac disease at high thromboembolism potential. The authors report a case of peripartum cardiomyopathy admitted for congestive heart failure. Echocardiography found a dilated cardiomyopathy with severely impaired left ventricular systolic function and biventricular thrombi. During hospitalization his condition was complicated by severe bilateral pulmonary embolism and left lower limb arterial acute thrombosis. The treatment consisted of thrombolysis with streptokinase associated with dobutamine (in addition to the conventional treatment of heart failure and bromocriptine). The outcome was favorable, marked by pulmonary and lower limb arterial unblocking. PMID:25623958

  7. Public Health Lessons from Severe Acute Respiratory Syndrome a Decade Later

    PubMed Central

    Butler-Jones, David; Tsang, Thomas; Yu, Wang

    2013-01-01

    The outbreak of severe acute respiratory syndrome in 2002–2003 exacted considerable human and economic costs from countries involved. It also exposed major weaknesses in several of these countries in coping with an outbreak of a newly emerged infectious disease. In the 10 years since the outbreak, in addition to the increase in knowledge of the biology and epidemiology of this disease, a major lesson learned is the value of having a national public health institute that is prepared to control disease outbreaks and designed to coordinate a national response and assist localities in their responses. PMID:23739634

  8. Delivery of In Vivo Acute Intermittent Hypoxia in Neonatal Rodents to Prime Subventricular Zone-derived Neural Progenitor Cell Cultures.

    PubMed

    Ross, Heather H; Sandhu, Milap S; Sharififar, Sharareh; Fuller, David D

    2015-01-01

    Extended culture of neural stem/progenitor cells facilitates in vitro analyses to understand their biology while enabling expansion of cell populations to adequate numbers prior to transplantation. Identifying approaches to refine this process, to augment the production of all CNS cell types (i.e., neurons), and to possibly contribute to therapeutic cell therapy protocols is a high research priority. This report describes an easily applied in vivo "pre-conditioning" stimulus which can be delivered to awake, non-anesthetized animals. Thus, it is a non-invasive and non-stressful procedure. Specifically described are the procedures for exposing mouse or rat pups (aged postnatal day 1-8) to a brief (40-80 min) period of intermittent hypoxia (AIH). The procedures included in this video protocol include calibration of the whole-body plethysmography chamber in which pups are placed during AIH and the technical details of AIH exposure. The efficacy of this approach to elicit tissue-level changes in the awake animal is demonstrated through the enhancement of subsequent in vitro expansion and neuronal differentiation in cells harvested from the subventricular zone (SVZ). These results support the notion that tissue level changes across multiple systems could be observed following AIH, and support the continued optimization and establishment of AIH as a priming or conditioning modality for therapeutic cell populations. PMID:26556530

  9. Traditional Chinese medicine, Qing Ying Tang, ameliorates the severity of acute lung injury induced by severe acute pancreatitis in rats via the upregulation of aquaporin-1

    PubMed Central

    GAO, ZHENMING; XU, JUNFENG; SUN, DEGUANG; ZHANG, RIXIN; LIANG, RUI; WANG, LIMING; FAN, RONG

    2014-01-01

    Aquaporin-1 (AQP-1) is expressed in lung endothelial cells and regulates water transport; thus, AQP-1 plays an important role in a number of edema-associated lung diseases. Qing Yin Tang (QYT), a traditional Chinese medicine, has been shown to effectively reduce the mortality rate of acute lung injury (ALI) induced by severe acute pancreatitis (SAP). The current study aimed to investigate the detailed mechanisms underlying the effects of QYT on ALI induced by SAP, particularly the effects on the expression levels of AQP-1 in the lung tissue. ALI was established in Wister rats who were subsequently divided into four groups: SHAM, ALI, dexamethasone (DEX) and QYT groups (n=8 per group). In the QYT group, 20 ml/kg QYT was administered by gavage immediately following the induction of SAP. Blood and lung tissues were collected 8 h following the induction of pancreatitis. The lung wet/dry ratio, as well as the levels of blood gases, serum amylase and tumor necrosis factor-α (TNF-α), were measured at 4, 8 and 12 h following SAP-associated ALI induction surgery. The expression levels of AQP-1 in the lung tissue were detected by quantitative polymerase chain reaction, immunohistochemistry and western blot analysis. No statistically significant differences were observed with regard to the levels of serum amylase, wet/dry ratio, partial pressure of oxygen, serum TNF-α and pathological changes in the pulmonary tissue between the QYT and DEX groups; however, a statistically significant difference was observed when compared with the ALI group. The expression levels of AQP-1 significantly increased (P<0.05) and lung edema was alleviated in the QYT and DEX groups, when compared with ALI group. Therefore, the expression level of AQP-1 is associated with pulmonary edema. QYT protects the lungs from injury induced by SAP via the upregulation of AQP-1, which suppresses TNF-α expression. PMID:25371738

  10. Traditional Chinese medicine, Qing Ying Tang, ameliorates the severity of acute lung injury induced by severe acute pancreatitis in rats via the upregulation of aquaporin-1.

    PubMed

    Gao, Zhenming; Xu, Junfeng; Sun, Deguang; Zhang, Rixin; Liang, Rui; Wang, Liming; Fan, Rong

    2014-12-01

    Aquaporin-1 (AQP-1) is expressed in lung endothelial cells and regulates water transport; thus, AQP-1 plays an important role in a number of edema-associated lung diseases. Qing Yin Tang (QYT), a traditional Chinese medicine, has been shown to effectively reduce the mortality rate of acute lung injury (ALI) induced by severe acute pancreatitis (SAP). The current study aimed to investigate the detailed mechanisms underlying the effects of QYT on ALI induced by SAP, particularly the effects on the expression levels of AQP-1 in the lung tissue. ALI was established in Wister rats who were subsequently divided into four groups: SHAM, ALI, dexamethasone (DEX) and QYT groups (n=8 per group). In the QYT group, 20 ml/kg QYT was administered by gavage immediately following the induction of SAP. Blood and lung tissues were collected 8 h following the induction of pancreatitis. The lung wet/dry ratio, as well as the levels of blood gases, serum amylase and tumor necrosis factor-α (TNF-α), were measured at 4, 8 and 12 h following SAP-associated ALI induction surgery. The expression levels of AQP-1 in the lung tissue were detected by quantitative polymerase chain reaction, immunohistochemistry and western blot analysis. No statistically significant differences were observed with regard to the levels of serum amylase, wet/dry ratio, partial pressure of oxygen, serum TNF-α and pathological changes in the pulmonary tissue between the QYT and DEX groups; however, a statistically significant difference was observed when compared with the ALI group. The expression levels of AQP-1 significantly increased (P<0.05) and lung edema was alleviated in the QYT and DEX groups, when compared with ALI group. Therefore, the expression level of AQP-1 is associated with pulmonary edema. QYT protects the lungs from injury induced by SAP via the upregulation of AQP-1, which suppresses TNF-α expression. PMID:25371738

  11. Melatonin prevents acute kidney injury in severely burned rats via the activation of SIRT1

    PubMed Central

    Bai, Xiao-Zhi; He, Ting; Gao, Jian-Xin; Liu, Yang; Liu, Jia-Qi; Han, Shi-Chao; Li, Yan; Shi, Ji-Hong; Han, Jun-Tao; Tao, Ke; Xie, Song-Tao; Wang, Hong-Tao; Hu, Da-Hai

    2016-01-01

    Acute kidney injury (AKI) is a common complication after severe burns. Melatonin has been reported to protect against multiple organ injuries by increasing the expression of SIRT1, a silent information regulator that regulates stress responses, inflammation, cellular senescence and apoptosis. This study aimed to investigate the protective effects of melatonin on renal tissues of burned rats and the role of SIRT1 involving the effects. Rat severely burned model was established, with or without the administration of melatonin and SIRT1 inhibitor. The renal function and histological manifestations were determined to evaluate the severity of kidney injury. The levels of acetylated-p53 (Ac-p53), acetylated-p65 (Ac-p65), NF-κB, acetylated-forkhead box O1 (Ac-FoxO1), Bcl-2 and Bax were analyzed to study the underlying mechanisms. Our results suggested that severe burns could induce acute kidney injury, which could be partially reversed by melatonin. Melatonin attenuated oxidative stress, inflammation and apoptosis accompanied by the increased expression of SIRT1. The protective effects of melatonin were abrogated by the inhibition of SIRT1. In conclusion, we demonstrate that melatonin improves severe burn-induced AKI via the activation of SIRT1 signaling. PMID:27599451

  12. Melatonin prevents acute kidney injury in severely burned rats via the activation of SIRT1.

    PubMed

    Bai, Xiao-Zhi; He, Ting; Gao, Jian-Xin; Liu, Yang; Liu, Jia-Qi; Han, Shi-Chao; Li, Yan; Shi, Ji-Hong; Han, Jun-Tao; Tao, Ke; Xie, Song-Tao; Wang, Hong-Tao; Hu, Da-Hai

    2016-01-01

    Acute kidney injury (AKI) is a common complication after severe burns. Melatonin has been reported to protect against multiple organ injuries by increasing the expression of SIRT1, a silent information regulator that regulates stress responses, inflammation, cellular senescence and apoptosis. This study aimed to investigate the protective effects of melatonin on renal tissues of burned rats and the role of SIRT1 involving the effects. Rat severely burned model was established, with or without the administration of melatonin and SIRT1 inhibitor. The renal function and histological manifestations were determined to evaluate the severity of kidney injury. The levels of acetylated-p53 (Ac-p53), acetylated-p65 (Ac-p65), NF-κB, acetylated-forkhead box O1 (Ac-FoxO1), Bcl-2 and Bax were analyzed to study the underlying mechanisms. Our results suggested that severe burns could induce acute kidney injury, which could be partially reversed by melatonin. Melatonin attenuated oxidative stress, inflammation and apoptosis accompanied by the increased expression of SIRT1. The protective effects of melatonin were abrogated by the inhibition of SIRT1. In conclusion, we demonstrate that melatonin improves severe burn-induced AKI via the activation of SIRT1 signaling. PMID:27599451

  13. Gastroesophageal Reflux Disease Increases Infant Acute Respiratory Illness Severity, but not Childhood Asthma.

    PubMed

    Valet, Robert S; Carroll, Kecia N; Gebretsadik, Tebeb; Minton, Patricia A; Woodward, Kimberly B; Liu, Zhouwen; Hartert, Tina V

    2014-03-01

    It is unknown whether gastroesophageal reflux disease (GERD) during infancy affects infant bronchiolitis severity or childhood asthma inception. Four hundred thirty-two infants presenting with acute respiratory illness due to bronchiolitis or upper respiratory infection were studied. The primary exposure was the parental report of a previous GERD diagnosis. Outcomes included bronchiolitis severity at initial presentation and childhood asthma diagnosis at age 4. Infants with parentally reported GERD had a higher bronchiolitis severity score (range=0-12, clinically significant difference=0.5), indicating more severe disease, than infants without reported GERD (median 5.5 [interquartile range 3.5-9.0] among those with reported GERD versus 4.0 [1.0-7.0] among those without, P=0.005). This association persisted after adjusting for infant age, race, gender, and secondhand smoke exposure by a propensity score (adjusted odds ratio [OR] 1.99, 95% confidence interval [CI] 1.14-3.46, P=0.02). The parental report of GERD during infancy was not associated with the parental report of asthma diagnosis at age 4. GERD during infancy may contribute to acute respiratory illness severity, but is not associated with asthma diagnosis at age 4. Future prospective studies are needed to confirm these findings. PMID:24669353

  14. Suppression of hypoxia-inducible factor-1alpha and its downstream genes reduces acute hyperglycemia-enhanced hemorrhagic transformation in a rat model of cerebral ischemia.

    PubMed

    Chen, Chunhua; Ostrowski, Robert P; Zhou, Changman; Tang, Jiping; Zhang, John H

    2010-07-01

    We evaluated a role of hypoxia-inducible factor-1alpha (HIF-1alpha) and its downstream genes in acute hyperglycemia-induced hemorrhagic transformation in a rat model of focal cerebral ischemia. Male Sprague-Dawley rats weighing 280-300 g (n = 105) were divided into sham, 90 min middle cerebral artery occlusion (MCAO), MCAO plus HIF-1alpha inhibitors, 2-methoxyestradiol (2ME2) or 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1), groups. Rats received an injection of 50% dextrose (6 ml/kg intraperitoneally) at 15 min before MCAO. HIF-1alpha inhibitors were administered at the onset of reperfusion. The animals were examined for neurological deficits and sacrificed at 6, 12, 24, and 72 hr following MCAO. The cerebral tissues were collected for histology, zymography, and Western blot analysis. The expression of HIF-1alpha was increased in ischemic brain tissues after MCAO and reduced by HIF-1alpha inhibitors. In addition, 2ME2 reduced the expression of vascular endothelial growth factor (VEGF) and the elevation of active matrix metalloproteinase-2 and -9 (MMP-2/MMP-9) in the ipsilateral hemisphere. Both 2ME2 and YC-1 reduced infarct volume and ameliorated neurological deficits. However, only 2ME2 attenuated hemorrhagic transformation in the ischemic territory. In conclusion, the inhibition of HIF-1alpha and its downstream genes attenuates hemorrhagic conversion of cerebral infarction and ameliorates neurological deficits after focal cerebral ischemia. PMID:20155812

  15. Sleep in the Acute Phase of Severe Traumatic Brain Injury: A Snapshot of Polysomnography.

    PubMed

    Wiseman-Hakes, Catherine; Duclos, Catherine; Blais, Hélène; Dumont, Marie; Bernard, Francis; Desautels, Alex; Menon, David K; Gilbert, Danielle; Carrier, Julie; Gosselin, Nadia

    2016-09-01

    Background and Objectives The onset of pervasive sleep-wake disturbances associated with traumatic brain injury (TBI) is poorly understood. This study aimed to (a) determine the feasibility of using polysomnography in patients in the acute, hospitalized stage of severe TBI and (b) explore sleep quality and sleep architecture during this stage of recovery, compared to patients with other traumatic injuries. Methods A cross-sectional case-control design was used. We examined the sleep of 7 patients with severe TBI (17-47 years; 20.3 ± 15.0 days postinjury) and 6 patients with orthopedic and/or spinal cord injuries (OSCI; 19-58 years; 16.9 ± 4.9 days postinjury). One night of ambulatory polysomnography was performed at bedside. Results Compared to OSCI patients, TBI patients showed a significantly longer duration of nocturnal sleep and earlier nighttime sleep onset. Sleep efficiency was low and comparable in both groups. All sleep stages were observed in both groups with normal proportions according to age. Conclusion Patients in the acute stage of severe TBI exhibit increased sleep duration and earlier sleep onset, suggesting that the injured brain enhances sleep need and/or decreases the ability to maintain wakefulness. As poor sleep efficiency could compromise brain recovery, further studies should investigate whether strategies known to optimize sleep in healthy individuals are efficacious in acute TBI. While there are several inherent challenges, polysomnography is a useful means of examining sleep in the early stage of recovery in patients with severe TBI. PMID:26704256

  16. Early enteral feeding in severe acute pancreatitis: can it prevent secondary pancreatic (super) infection?

    PubMed

    Lehocky, P; Sarr, M G

    2000-01-01

    Sepsis continues to account for a second peak in mortality in patients with severe acute pancreatitis. The prevention of these septic complications and subsequent development of multiple organ dysfunction syndrome remains a major focus for investigators, yet despite considerable clinical and experimental work addressing its etiology, septic complications remain high. Several studies have been designed to demonstrate the mechanism of origin of these septic complications with an attempt to define strategies for their prevention to improve patient outcomes. There is clear evidence that the origin of this secondary bacterial infection arises from enteric bacterial translocation secondary to disruption of the gut mucosal barrier during acute pancreatitis. Strategies designed to prevent secondary pancreatic infection include aggressive fluid resuscitation to maximize organ perfusion, early systemic antibiotic treatment or selective gut decontamination, and recently attempts to block mediators of the systemic inflammatory response. This discussion will summarize our present understanding of the etiopathogenesis of secondary bacterial 'superinfection' of necrotizing pancreatitis and how the initiation of enteral feeding early in the course of acute pancreatitis may prove to be an effective means of preventing and/or reversing the breakdown of the gut mucosal defense barrier. PMID:11155001

  17. Severity of Spatial Neglect During Acute Inpatient Rehabilitation Predicts Community Mobility After Stroke

    PubMed Central

    Oh-Park, Mooyeon; Hung, Cynthia; Chen, Peii; Barrett, A.M.

    2014-01-01

    Objective To examine whether stroke survivors with more severe spatial neglect during their acute inpatient rehabilitation had poorer mobility after returning to their communities. Design A prospective observational study. Setting Acute inpatient rehabilitation and follow-up in the community. Participants Thirty-one consecutive stroke survivors with right-brain damage (women, n = 15 [48.4%]), with the mean (standard deviation) age of 60 ± 11.5 years, were included in the study if they demonstrated spatial neglect within 2 months after stroke. Methods Spatial neglect was assessed with the Behavioral Inattention Test (BIT) (range, 0-146 [a lower score indicates more severity]) and the Catherine Bergego Scale (range, 0-30 [a higher score indicates more severity]). A score of the Behavioral Inattention Test <129 or of the Catherine Bergego Scale >0 defined the presence of spatial neglect. Main Outcome Measurements The outcome measure is community mobility, defined by the extent and frequency of traveling within the home and in the community, and is assessed with the University of Alabama at Birmingham Study of Aging Life-Space Assessment (range, 0-120 [a lower score indicates less mobile]). This measure was assessed after participants returned home ≥6 months after stroke. The covariates were age, gender, functional independence at baseline; follow-up interval; and depressed mood, which may affect the relationship between spatial neglect and community mobility. Results A lower Behavioral Inattention Test score was a significant predictor of a lower Life-Space Assessment score after controlling for all the covariates (β = 0.009 [95% confidence interval, 0.008-0.017]); P = .020). The proportion of participants unable to travel independently beyond their homes was 0%, 27.3%, and 72.7% for those with mild, moderate, and severe acute neglect, respectively (Catherine Bergego Scale range, 1-10, 11-20, and 21-30, respectively). Conclusions Our result indicates that acute

  18. Controlled clinical trial of selective decontamination for the treatment of severe acute pancreatitis.

    PubMed Central

    Luiten, E J; Hop, W C; Lange, J F; Bruining, H A

    1995-01-01

    OBJECTIVE: A randomized, controlled, multicenter trial was undertaken in 102 patients with objective evidence of severe acute pancreatitis to evaluate whether selective decontamination reduces mortality. SUMMARY BACKGROUND DATA: Secondary pancreatic infection is the major cause of death in patients with acute necrotizing pancreatitis. Controlled clinical trials to study the effect of selective decontamination in such patients are not available. METHODS: Between April 22, 1990 and April 19, 1993, 102 patients with severe acute pancreatitis were admitted to 16 participating hospitals. Patients were entered into the study if severe acute pancreatitis was indicated, on admission, by multiple laboratory criteria (Imrie score > or = 3) and/or computed tomography criteria (Balthazar grade D or E). Patients were randomly assigned to receive standard treatment (control group) or standard treatment plus selective decontamination (norfloxacin, colistin, amphotericin; selective decontamination group). All patients received full supportive treatment, and surveillance cultures were taken in both groups. RESULTS: Fifty patients were assigned to the selective decontamination group and 52 were assigned to the control group. There were 18 deaths in the control group (35%), compared with 11 deaths (22%) in the selective decontamination group (adjusted for Imrie score and Balthazar grade: p = 0.048). This difference was mainly caused by a reduction of late mortality (> 2 weeks) due to significant reduction of gram-negative pancreatic infection (p = 0.003). The average number of laparotomies per patient was reduced in patients treated with selective decontamination (p < 0.05). Failure of selective decontamination to prevent secondary gram-negative pancreatic infection with subsequent death was seen in only three patients (6%) and transient gram-negative pancreatic infection was seen in one (2%). In both groups of patients, all gram-negative aerobic pancreatic infection was preceded by

  19. Progressive hypoxia decouples activity and aerobic performance of skate embryos

    PubMed Central

    Di Santo, Valentina; Tran, Anna H.; Svendsen, Jon C.

    2016-01-01

    Although fish population size is strongly affected by survival during embryonic stages, our understanding of physiological responses to environmental stressors is based primarily on studies of post-hatch fishes. Embryonic responses to acute exposure to changes in abiotic conditions, including increase in hypoxia, could be particularly important in species exhibiting long developmental time, as embryos are unable to select a different environment behaviourally. Given that oxygen is key to metabolic processes in fishes and aquatic hypoxia is becoming more severe and frequent worldwide, organisms are expected to reduce their aerobic performance. Here, we examined the metabolic and behavioural responses of embryos of a benthic elasmobranch fish, the little skate (Leucoraja erinacea), to acute progressive hypoxia, by measuring oxygen consumption and movement (tail-beat) rates inside the egg case. Oxygen consumption rates were not significantly affected by ambient oxygen levels until reaching 45% air saturation (critical oxygen saturation, Scrit). Below Scrit, oxygen consumption rates declined rapidly, revealing an oxygen conformity response. Surprisingly, we observed a decoupling of aerobic performance and activity, as tail-beat rates increased, rather than matching the declining metabolic rates, at air saturation levels of 55% and below. These results suggest a significantly divergent response at the physiological and behavioural levels. While skate embryos depressed their metabolic rates in response to progressive hypoxia, they increased water circulation inside the egg case, presumably to restore normoxic conditions, until activity ceased abruptly around 9.8% air saturation. PMID:27293746

  20. Central role of neutrophil in the pathogenesis of severe acute pancreatitis

    PubMed Central

    Yang, Zhi-wen; Meng, Xiao-xiao; Xu, Ping

    2015-01-01

    Severe acute pancreatitis (SAP) is an acute abdominal disease with the strong systemic inflammatory response, and rapidly progresses from a local pancreatic damage into multiple organ dysfunction. For many decades, the contributions of neutrophils to the pathology of SAP were traditionally thought to be the chemokine and cytokine cascades that accompany inflammation. In this review, we focus mainly on those recently recognized aspects of neutrophils in SAP processes. First, emerging evidence suggests that therapeutic interventions targeting neutrophils significantly lower tissue damage and protect against the occurrence of pancreatitis. Second, trypsin activation promotes the initial neutrophils recruitment into local pancreas, and subsequently neutrophils infiltration in turn triggers trypsin production. Finally, neutrophils have the unique ability to release neutrophil extracellular traps even in the absence of pathogens. PMID:26249268

  1. Nicardipine-induced acute pulmonary edema: a rare but severe complication of tocolysis.

    PubMed

    Serena, Claire; Begot, Emmanuelle; Cros, Jérôme; Hodler, Charles; Fedou, Anne Laure; Nathan-Denizot, Nathalie; Clavel, Marc

    2014-01-01

    We report four cases of acute pulmonary edema that occurred during treatment by intravenous tocolysis using nicardipine in pregnancy patients with no previous heart problems. Clinical severity justified hospitalization in intensive care unit (ICU) each time. Acute dyspnea has begun at an average of 63 hours after initiation of treatment. For all patients, the first diagnosis suspected was pulmonary embolism. The patients' condition improved rapidly with appropriate diuretic treatment and by modifying the tocolysis. The use of intravenous nicardipine is widely used for tocolysis in France even if its prescription does not have a marketing authorization. The pathophysiological mechanisms of this complication remain unclear. The main reported risk factors are spontaneous preterm labor, multiple pregnancy, concomitant obstetrical disease, association with beta-agonists, and fetal lung maturation corticotherapy. A better knowledge of this rare but serious adverse event should improve the management of patients. Nifedipine or atosiban, the efficiency of which tocolysis was also studied, could be an alternative. PMID:25215245

  2. Central role of neutrophil in the pathogenesis of severe acute pancreatitis.

    PubMed

    Yang, Zhi-Wen; Meng, Xiao-Xiao; Xu, Ping

    2015-11-01

    Severe acute pancreatitis (SAP) is an acute abdominal disease with the strong systemic inflammatory response, and rapidly progresses from a local pancreatic damage into multiple organ dysfunction. For many decades, the contributions of neutrophils to the pathology of SAP were traditionally thought to be the chemokine and cytokine cascades that accompany inflammation. In this review, we focus mainly on those recently recognized aspects of neutrophils in SAP processes. First, emerging evidence suggests that therapeutic interventions targeting neutrophils significantly lower tissue damage and protect against the occurrence of pancreatitis. Second, trypsin activation promotes the initial neutrophils recruitment into local pancreas, and subsequently neutrophils infiltration in turn triggers trypsin production. Finally, neutrophils have the unique ability to release neutrophil extracellular traps even in the absence of pathogens. PMID:26249268

  3. Nicardipine-Induced Acute Pulmonary Edema: A Rare but Severe Complication of Tocolysis

    PubMed Central

    Serena, Claire; Begot, Emmanuelle; Cros, Jérôme; Hodler, Charles; Fedou, Anne Laure; Nathan-Denizot, Nathalie; Clavel, Marc

    2014-01-01

    We report four cases of acute pulmonary edema that occurred during treatment by intravenous tocolysis using nicardipine in pregnancy patients with no previous heart problems. Clinical severity justified hospitalization in intensive care unit (ICU) each time. Acute dyspnea has begun at an average of 63 hours after initiation of treatment. For all patients, the first diagnosis suspected was pulmonary embolism. The patients' condition improved rapidly with appropriate diuretic treatment and by modifying the tocolysis. The use of intravenous nicardipine is widely used for tocolysis in France even if its prescription does not have a marketing authorization. The pathophysiological mechanisms of this complication remain unclear. The main reported risk factors are spontaneous preterm labor, multiple pregnancy, concomitant obstetrical disease, association with beta-agonists, and fetal lung maturation corticotherapy. A better knowledge of this rare but serious adverse event should improve the management of patients. Nifedipine or atosiban, the efficiency of which tocolysis was also studied, could be an alternative. PMID:25215245

  4. Spectral-domain optical coherence tomography features of mild and severe acute solar retinopathy.

    PubMed

    Hossein, Mohammad; Jabbarpoor Bonyadi, Mohammad Hossein; Bonyadi, Jabbarpour; Soheilian, Rasam; Soheilian, Masoud; Peyman, Gholam A

    2011-01-01

    Photochemical/thermal retinal damage that results from unprotected solar eclipse viewing has vague presentations and sometimes misleading diagnosis, especially in cases with unclear history. Spectral-domain optical coherence tomography (SD-OCT) is a non-invasive imaging technique useful in differential diagnosis that can reveal characteristic foveal alterations in solar retinopathy to an unprecedented quasi histologic level. The authors present high-resolution SD-OCT findings correlated with clinical findings in three eyes of two cases with acute solar retinopathy. SD-OCT can precisely define the site and extent of damage in acute solar retinopathy. In mild forms, damage may be limited to the outer retina with inner segment/outer segment disruption. In severe forms, full thickness macular damage may be seen. Advances in retinal imaging have improved our ability to provide precise correlation with clinical presentation and prognosis. PMID:21899248

  5. Radial EUS Examination Can be Helpful in Predicting the Severity of Acute Biliary Pancreatitis.

    PubMed

    Alper, Emrah; Arabul, Mahmut; Aslan, Fatih; Cekic, Cem; Celik, Mustafa; Ipek, Serkan; Unsal, Belkis

    2016-01-01

    We investigated the utility of noncontrast enhanced endosonography (EUS) in predicting the severity of acute pancreatitis (AP) during the first 72 to 96 h of admission.In total, 187 patients with acute biliary pancreatitis were included. The patients were classified into 2 groups as having severe and mild AP according to the Modified Glasgow scoring and computerized tomography severity index (SI). The 158 cases with mild and 29 cases with severe AP had a similar age and sex distribution.Although none of the cases with mild AP developed morbidity and death, of the cases with severe AP, 16 developed serious morbidities and 5 died. On EUS examination, we looked for parenchymal findings, peripancreatic inflammatory signs, free or loculated fluid collections, and abnormalities of the common bile duct and the pancreatic channel. Statistical analysis indicated a significant relationship between the severity of AP with diffuse parenchymal edema, periparenchymal plastering, and/or diffuse retroperitoneal free fluid accumulation, and peri-pancreatic edema. We also defined an EUSSI and found that the EUSSI had sensitivity of 89.7%, specificity of 84.2%, positive predictivity value (PPV) of 88.9%, negative predictivity value (NPV) of 91.2%, and an accuracy of 87.9% in the differentiation of mild and severe AP. We found that the EUSSI had an accuracy of 72.4%, sensitivity of 75.4%, specificity of 65.1%, PPV of 69.3%, and NPV of 73.1% for determining mortality.Our data suggest that EUS allowed us to accurately predict the severity and mortality in nearly 90% of cases with AP. PMID:26817865

  6. Acute Kidney Injury Is Common in Pediatric Severe Malaria and Is Associated With Increased Mortality.

    PubMed

    Conroy, Andrea L; Hawkes, Michael; Elphinstone, Robyn E; Morgan, Catherine; Hermann, Laura; Barker, Kevin R; Namasopo, Sophie; Opoka, Robert O; John, Chandy C; Liles, W Conrad; Kain, Kevin C

    2016-03-01

    Background.  Acute kidney injury (AKI) is a well recognized complication of severe malaria in adults, but the incidence and clinical importance of AKI in pediatric severe malaria (SM) is not well documented. Methods.  One hundred eighty children aged 1 to 10 years with SM were enrolled between 2011 and 2013 in Uganda. Kidney function was monitored daily for 4 days using serum creatinine (Cr). Acute kidney injury was defined using the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Blood urea nitrogen (BUN) and Cr were assessed using i-STAT, and cystatin C (CysC) was measured by enzyme-linked immunosorbent assay. Results.  Eighty-one (45.5%) children had KDIGO-defined AKI in the study: 42 (51.9%) stage 1, 18 (22.2%) stage 2, and 21 (25.9%) stage 3. Acute kidney injury evolved or developed in 50% of children after admission of hospital. There was an increased risk of AKI in children randomized to inhaled nitric oxide (iNO), with 47 (54.0%) of children in the iNO arm developing AKI compared with 34 (37.4%) in the placebo arm (relative risk, 1.36; 95% confidence interval [CI], 1.03-1.80). Duration of hospitalization increased across stages of AKI (P = .002). Acute kidney injury was associated with neurodisability at discharge in the children receiving placebo (25% in children with AKI vs 1.9% in children with no AKI, P = .002). Mortality increased across stages of AKI (P = .006) in the placebo arm, reaching 37.5% in stage 3 AKI. Acute kidney injury was not associated with neurodisability or mortality at discharge in children receiving iNO (P > .05 for both). Levels of kidney biomarkers were predictive of mortality with areas under the curves (AUCs) of 0.80 (95% CI, .65-.95; P = .006) and 0.72 (95% CI, .57-.87; P < .001), respectively. Admission levels of CysC and BUN were elevated in children who died by 6 months (P < .0001 and P = .009, respectively). Conclusions.  Acute kidney injury is an underrecognized complication in young children with SM

  7. Acute Kidney Injury Is Common in Pediatric Severe Malaria and Is Associated With Increased Mortality

    PubMed Central

    Conroy, Andrea L.; Hawkes, Michael; Elphinstone, Robyn E.; Morgan, Catherine; Hermann, Laura; Barker, Kevin R.; Namasopo, Sophie; Opoka, Robert O.; John, Chandy C.; Liles, W. Conrad; Kain, Kevin C.

    2016-01-01

    Background. Acute kidney injury (AKI) is a well recognized complication of severe malaria in adults, but the incidence and clinical importance of AKI in pediatric severe malaria (SM) is not well documented. Methods. One hundred eighty children aged 1 to 10 years with SM were enrolled between 2011 and 2013 in Uganda. Kidney function was monitored daily for 4 days using serum creatinine (Cr). Acute kidney injury was defined using the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Blood urea nitrogen (BUN) and Cr were assessed using i-STAT, and cystatin C (CysC) was measured by enzyme-linked immunosorbent assay. Results. Eighty-one (45.5%) children had KDIGO-defined AKI in the study: 42 (51.9%) stage 1, 18 (22.2%) stage 2, and 21 (25.9%) stage 3. Acute kidney injury evolved or developed in 50% of children after admission of hospital. There was an increased risk of AKI in children randomized to inhaled nitric oxide (iNO), with 47 (54.0%) of children in the iNO arm developing AKI compared with 34 (37.4%) in the placebo arm (relative risk, 1.36; 95% confidence interval [CI], 1.03–1.80). Duration of hospitalization increased across stages of AKI (P = .002). Acute kidney injury was associated with neurodisability at discharge in the children receiving placebo (25% in children with AKI vs 1.9% in children with no AKI, P = .002). Mortality increased across stages of AKI (P = .006) in the placebo arm, reaching 37.5% in stage 3 AKI. Acute kidney injury was not associated with neurodisability or mortality at discharge in children receiving iNO (P > .05 for both). Levels of kidney biomarkers were predictive of mortality with areas under the curves (AUCs) of 0.80 (95% CI, .65–.95; P = .006) and 0.72 (95% CI, .57–.87; P < .001), respectively. Admission levels of CysC and BUN were elevated in children who died by 6 months (P < .0001 and P = .009, respectively). Conclusions. Acute kidney injury is an underrecognized complication in young children with SM

  8. A murine model of obesity implicates the adipokine milieu in the pathogenesis of severe acute pancreatitis.

    PubMed

    Zyromski, Nicholas J; Mathur, Abhishek; Pitt, Henry A; Lu, Debao; Gripe, John T; Walker, Julia J; Yancey, Kyle; Wade, Terence E; Swartz-Basile, Deborah A

    2008-09-01

    Obesity is clearly an independent risk factor for increased severity of acute pancreatitis (AP), although the mechanisms underlying this association are unknown. Adipokines (including leptin and adiponectin) are pleiotropic molecules produced by adipocytes that are important regulators of the inflammatory response. We hypothesized that the altered adipokine milieu observed in obesity contributes to the increased severity of pancreatitis. Lean (C57BL/6J), obese leptin-deficient (LepOb), and obese hyperleptinemic (LepDb) mice were subjected to AP by six hourly intraperitoneal injections of cerulein (50 microg/kg). Severity of AP was assessed by histology and by measuring pancreatic concentration of the proinflammatory cytokines IL-1beta and IL-6, the chemokine MCP-1, and the marker of neutrophil activation MPO. Both congenitally obese strains of mice developed significantly more severe AP than wild-type lean animals. Severity of AP was not solely related to adipose tissue volume: LepOb mice were heaviest; however, LepDb mice developed the most severe AP both histologically and biochemically. Circulating adiponectin concentrations inversely mirrored the severity of pancreatitis. These data demonstrate that congenitally obese mice develop more severe AP than lean animals when challenged by cerulein hyperstimulation and suggest that alteration of the adipokine milieu exacerbates the severity of AP in obesity. PMID:18583460

  9. Cathelicidin-related antimicrobial peptide modulates the severity of acute pancreatitis in mice

    PubMed Central

    DENG, YUAN-YUAN; SHAMOON, MUHAMMAD; HE, YUE; BHATIA, MADHAV; SUN, JIA

    2016-01-01

    The present study aimed to investigate the immunomodulatory effects of mouse cathelicidin-related antimicrobial peptide (CRAMP) on experimental acute pancreatitis (AP). AP is a common clinical condition characterized by acute abdominal inflammation. Innate immune cells and mediators are intrinsically linked to the pathogenesis of AP. Cathelicidins are innate immunity-derived antimicrobial peptides that exert immunomodulatory effects on various host cells. However, how cathelicidins are involved and modulate the severity and inflammatory responses of AP remains unclear. In the present study, the mouse CRAMP gene-deficient cnlp−/− mice and their wild-type C57BL/6J littermates were induced with AP by multiple hourly injections of supramaximal doses of caerulein. Serum amylase levels, pancreatic myeloperoxidase activity and histological examination were performed in order to determine the disease severity and the levels of inflammatory cytokines. Disease severity and inflammatory markers were subsequently evaluated in the control mice, cnlp−/− C57BL/6J mice with AP, and wild-type C57BL/6J mice with AP. The results demonstrated that cnlp−/− mice exhibited a more severe phenotype and inflammatory response following AP induction compared with the wild-type mice, as evidenced by increased serum amylase levels, pancreatic myeloperoxidase release, and early inflammatory mediator tumor necrosis factor-α production. Histological examination confirmed that CRAMP deficiency worsened the pancreatic inflammatory condition. These results indicate that CRAMP may be considered a novel modulatory mediator in mouse experimental AP. PMID:27035328

  10. Cathelicidin-related antimicrobial peptide modulates the severity of acute pancreatitis in mice.

    PubMed

    Deng, Yuan-Yuan; Shamoon, Muhammad; He, Yue; Bhatia, Madhav; Sun, Jia

    2016-05-01

    The present study aimed to investigate the immunomodulatory effects of mouse cathelicidin-related antimicrobial peptide (CRAMP) on experimental acute pancreatitis (AP). AP is a common clinical condition characterized by acute abdominal inflammation. Innate immune cells and mediators are intrinsically linked to the pathogenesis of AP. Cathelicidins are innate immunity-derived antimicrobial peptides that exert immunomodulatory effects on various host cells. However, how cathelicidins are involved and modulate the severity and inflammatory responses of AP remains unclear. In the present study, the mouse CRAMP gene‑deficient cnlp‑/‑ mice and their wild‑type C57BL/6J littermates were induced with AP by multiple hourly injections of supramaximal doses of caerulein. Serum amylase levels, pancreatic myeloperoxidase activity and histological examination were performed in order to determine the disease severity and the levels of inflammatory cytokines. Disease severity and inflammatory markers were subsequently evaluated in the control mice, cnlp‑/‑ C57BL/6J mice with AP, and wild‑type C57BL/6J mice with AP. The results demonstrated that cnlp‑/‑ mice exhibited a more severe phenotype and inflammatory response following AP induction compared with the wild‑type mice, as evidenced by increased serum amylase levels, pancreatic myeloperoxidase release, and early inflammatory mediator tumor necrosis factor‑α production. Histological examination confirmed that CRAMP deficiency worsened the pancreatic inflammatory condition. These results indicate that CRAMP may be considered a novel modulatory mediator in mouse experimental AP. PMID:27035328

  11. Imaging hypoxia in gliomas

    PubMed Central

    Mendichovszky, I; Jackson, A

    2011-01-01

    Hypoxia plays a central role in tumour development, angiogenesis, growth and resistance to treatment. Owing to constant developments in medical imaging technology, significant advances have been made towards in vitro and in vivo imaging of hypoxia in a variety of tumours, including gliomas of the central nervous system. The aim of this article is to review the literature on imaging approaches currently available for measuring hypoxia in human gliomas and provide an insight into recent advances and future directions in this field. After a brief overview of hypoxia and its importance in gliomas, several methods of measuring hypoxia will be presented. These range from invasive monitoring by Eppendorf polarographic O2 microelectrodes, positron electron tomography (PET) tracers based on 2-nitroimidazole compounds [18F-labelled fluoro-misonidazole (18F-MISO) or 1-(2-[(18)F]fluoro-1-[hydroxymethyl]ethoxy)methyl-2-nitroimidazole (FRP-170)], 64Cu-ATSM Cu-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) or 99mTc- and 68Ga-labelled metronidazole (MN) agents to advanced MRI methods, such as blood oxygenation level dependent (BOLD) MRI, oxygen-enhanced MRI, diffusion-weighted MRI (DWI-MRI), dynamic contrast-enhanced MRI (DCE-MRI) and 1H-magnetic resonance spectroscopy. PMID:22433825

  12. Rat reaction to hypokinesia after prior adaptation to hypoxia

    NASA Technical Reports Server (NTRS)

    Barashova, Z. I.; Tarakanova, O. I.

    1980-01-01

    The effect of prior hypoxia adaptation on body tolerance to hypokinesia was investigated. Rats trained to a 50 day period of hypokinesia and hypoxia with a preliminary month of adaptation to hypoxia showed less weight loss, higher indices for red blood content, heightened reactivity of the overall organism and the central nervous system to acute hypoxia, and decreased modification of the skeletal muscles compared to rats subjected to hypokinesia alone.

  13. Acute Serum Hormone Levels: Characterization and Prognosis after Severe Traumatic Brain Injury

    PubMed Central

    McCullough, Emily H.; Niyonkuru, Christian; Ozawa, Haishin; Loucks, Tammy L.; Dobos, Julie A.; Brett, Christopher A.; Santarsieri, Martina; Dixon, C. Edward; Berga, Sarah L.; Fabio, Anthony

    2011-01-01

    Abstract Experimental traumatic brain injury (TBI) studies report the neuroprotective effects of female sex steroids on multiple mechanisms of injury, with the clinical assumption that women have hormonally mediated neuroprotection because of the endogenous presence of these hormones. Other literature indicates that testosterone may exacerbate injury. Further, stress hormone abnormalities that accompany critical illness may both amplify or blunt sex steroid levels. To better understand the role of sex steroid exposure in mediating TBI, we 1) characterized temporal profiles of serum gonadal and stress hormones in a population with severe TBI during the acute phases of their injury; and 2) used a biological systems approach to evaluate these hormones as biomarkers predicting global outcome. The study population was 117 adults (28 women; 89 men) with severe TBI. Serum samples (n=536) were collected for 7 days post-TBI for cortisol, progesterone, testosterone, estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Hormone data were linked with clinical data, including acute care mortality and Glasgow Outcome Scale (GOS) scores at 6 months. Hormone levels after TBI were compared to those in healthy controls (n=14). Group based trajectory analysis (TRAJ) was used to develop temporal hormone profiles that delineate distinct subpopulations in the cohort. Structural equations models were used to determine inter-relationships between hormones and outcomes within a multivariate model. Compared to controls, acute serum hormone levels were significantly altered after severe TBI. Changes in the post-TBI adrenal response and peripheral aromatization influenced hormone TRAJ profiles and contributed to the abnormalities, including increased estradiol in men and increased testosterone in women. In addition to older age and greater injury severity, increased estradiol and testosterone levels over time were associated with increased mortality and worse global

  14. Acute serum hormone levels: characterization and prognosis after severe traumatic brain injury.

    PubMed

    Wagner, Amy K; McCullough, Emily H; Niyonkuru, Christian; Ozawa, Haishin; Loucks, Tammy L; Dobos, Julie A; Brett, Christopher A; Santarsieri, Martina; Dixon, C Edward; Berga, Sarah L; Fabio, Anthony

    2011-06-01

    Experimental traumatic brain injury (TBI) studies report the neuroprotective effects of female sex steroids on multiple mechanisms of injury, with the clinical assumption that women have hormonally mediated neuroprotection because of the endogenous presence of these hormones. Other literature indicates that testosterone may exacerbate injury. Further, stress hormone abnormalities that accompany critical illness may both amplify or blunt sex steroid levels. To better understand the role of sex steroid exposure in mediating TBI, we 1) characterized temporal profiles of serum gonadal and stress hormones in a population with severe TBI during the acute phases of their injury; and 2) used a biological systems approach to evaluate these hormones as biomarkers predicting global outcome. The study population was 117 adults (28 women; 89 men) with severe TBI. Serum samples (n=536) were collected for 7 days post-TBI for cortisol, progesterone, testosterone, estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Hormone data were linked with clinical data, including acute care mortality and Glasgow Outcome Scale (GOS) scores at 6 months. Hormone levels after TBI were compared to those in healthy controls (n=14). Group based trajectory analysis (TRAJ) was used to develop temporal hormone profiles that delineate distinct subpopulations in the cohort. Structural equations models were used to determine inter-relationships between hormones and outcomes within a multivariate model. Compared to controls, acute serum hormone levels were significantly altered after severe TBI. Changes in the post-TBI adrenal response and peripheral aromatization influenced hormone TRAJ profiles and contributed to the abnormalities, including increased estradiol in men and increased testosterone in women. In addition to older age and greater injury severity, increased estradiol and testosterone levels over time were associated with increased mortality and worse global outcome for

  15. 17β-Estradiol mediates superior adaptation of right ventricular function to acute strenuous exercise in female rats with severe pulmonary hypertension.

    PubMed

    Lahm, Tim; Frump, Andrea L; Albrecht, Marjorie E; Fisher, Amanda J; Cook, Todd G; Jones, Thomas J; Yakubov, Bakhtiyor; Whitson, Jordan; Fuchs, Robyn K; Liu, Aiping; Chesler, Naomi C; Brown, M Beth

    2016-08-01

    17β-Estradiol (E2) exerts protective effects on right ventricular (RV) function in pulmonary arterial hypertension (PAH). Since acute exercise-induced increases in afterload may lead to RV dysfunction in PAH, we sought to determine whether E2 allows for superior RV adaptation after an acute exercise challenge. We studied echocardiographic, hemodynamic, structural, and biochemical markers of RV function in male and female rats with sugen/hypoxia (SuHx)-induced pulmonary hypertension, as well as in ovariectomized (OVX) SuHx females, with or without concomitant E2 repletion (75 μg·kg(-1)·day(-1)) immediately after 45 min of treadmill running at 75% of individually determined maximal aerobic capacity (75% aerobic capacity reserve). Compared with males, intact female rats exhibited higher stroke volume and cardiac indexes, a strong trend for better RV compliance, and less pronounced increases in indexed total pulmonary resistance. OVX abrogated favorable RV adaptations, whereas E2 repletion after OVX markedly improved RV function. E2's effects on pulmonary vascular remodeling were complex and less robust than its RV effects. Postexercise hemodynamics in females with endogenous or exogenous E2 were similar to hemodynamics in nonexercised controls, whereas OVX rats exhibited more severely altered postexercise hemodynamics. E2 mediated inhibitory effects on RV fibrosis and attenuated increases in RV collagen I/III ratio. Proapoptotic signaling, endothelial nitric oxide synthase phosphorylation, and autophagic flux markers were affected by E2 depletion and/or repletion. Markers of impaired autophagic flux correlated with endpoints of RV structure and function. Endogenous and exogenous E2 exerts protective effects on RV function measured immediately after an acute exercise challenge. Harnessing E2's mechanisms may lead to novel RV-directed therapies. PMID:27288487

  16. A scoring system for assessing the severity of acute diarrhea of adult patients

    PubMed Central

    Xiao, Hong-li; Ma, Su-xia; Qi, Hai-yu; Li, Xiaoli; Wang, Yan; Yin, Cheng-hong

    2016-01-01

    BACKGROUND: Diarrhea is frequently seen in developed and developing countries, and severe diarrhea is characterized by the high risk of death. Thus, it is very important to assess the severity of diarrhea early. We conducted a multi-center study to identify risk factors for the severity of diarrhea in adult patients and formulate an adult diarrhea state score (ADSS) for out-patient clinicians. METHODS: A total of 219 adult patients with acute diarrhea were divided into two groups: 132 patients with mild diarrhea and 87 with severe diarrhea. Logistic regression was used to determine risk factors for the severity of diarrhea. The risk factors were assessed and an ADSS was formulated. Receiver operating characteristic (ROC) analysis was made to evaluate the diagnostic accuracy of ADSS, and the Kappa test was used to confirm the diagnostic reliability. RESULTS: Five risk factors for evaluating the severity of diarrhea in adults included age (P<0.05), axillary temperature (P<0.01), mean arterial pressure (P<0.01), white blood cell count (WBC; P<0.01), and WBC in stool (P<0.01). The area under the ROC curve for ADSS was 0.958 when the cut off value was 4 (a sensitivity of 0.909; a specificity of 0.874), and the Kappa value was 0.781 (P<0.05). CONCLUSION: The risk factors associated with the pathogenic condition of diarrhea were identified, quantified and formulated into an ADSS, which has high diagnostic accuracy and reliability for the early identification of patients with severe acute diarrhea. PMID:27313808

  17. Evaluation of the properties and reliability of a clinical severity scale for acute asthma in children.

    PubMed

    Bishop, J; Carlin, J; Nolan, T

    1992-01-01

    The inter-observer agreement (reliability) and validity of a clinical asthma severity scale (ASS) derived from separate scores of wheeze, heart rate and accessory muscle use (each on a 4-point scale) were studied in 60 children aged between 6 months and 17 years (mean 5.4 years). Independent assessments of these clinical parameters were made by two paediatricians, and they also rated patients as having a mild, moderate, severe or very severe acute episode (clinical judgement rating, CJR). Oxygen saturation (SaO2) was measured concurrently by a Biox 3700 pulse oximeter and readings were categorized as mild (SaO2 greater than or equal to 94%), moderate (91-93%) and severe (less than 91%). Agreement between clinicians was assessed by the weighted kappa statistic (kappa W). Agreement for the ASS score compared to the severity grade obtained from SaO2 was slight (kappa W = 0.34) and compared to CJR the kappa W was 0.55. An ASS score of moderate or worse (greater than 3) had sensitivity of 97% and specificity of 50% for prediction of admission. The maximum frequency and duration of nebulizer therapy following admission were significantly greater for severe patients than for moderate patients. Length of hospital stay did not reflect the ASS score in the emergency department but total duration of functional disability increased with ASS score. The substitution of an adjusted heart rate score for the raw heart rate score used in ASS detracted from scale performance. The ASS is an imprecise but reasonable quantitative measure of the severity of an acute episode of asthma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1738014

  18. Diarrhoea Complicating Severe Acute Malnutrition in Kenyan Children: A Prospective Descriptive Study of Risk Factors and Outcome

    PubMed Central

    Talbert, Alison; Thuo, Nahashon; Karisa, Japhet; Chesaro, Charles; Ohuma, Eric; Ignas, James; Berkley, James A.; Toromo, Christopher; Atkinson, Sarah; Maitland, Kathryn

    2012-01-01

    Background Severe acute malnutrition (SAM) accounts for two million deaths worldwide annually. In those hospitalised with SAM, concomitant infections and diarrhoea are frequent complications resulting in adverse outcome. We examined the clinical and laboratory features on admission and outcome of children with SAM and diarrhoea at a Kenyan district hospital. Methods A 4-year prospective descriptive study involving 1,206 children aged 6 months to 12 years, hospitalized with SAM and managed in accordance with WHO guidelines. Data on clinical features, haematological, biochemical and microbiological findings for children with diarrhoea (≥3 watery stools/day) were systematically collected and analyzed to identify risk factors associated with poor outcome. Results At admission 592 children (49%) had diarrhoea of which 122 (21%) died compared to 72/614 (12%) deaths in those without diarrhoea at admission (Χ2 = 17.6 p<0.001). A further 187 (16%) children developed diarrhoea after 48 hours of admission and 33 died (18%). Any diarrhoea during admission resulted in a significantly higher mortality 161/852 (19%) than those uncomplicated by diarrhoea 33/351 (9%) (Χ2 = 16.6 p<0.001). Features associated with a fatal outcome in children presenting with diarrhoea included bacteraemia, hyponatraemia, low mid-upper arm circumference <10 cm, hypoxia, hypokalaemia and oedema. Bacteraemia had the highest risk of death (adjusted OR 6.1; 95% C.I 2.3, 16.3 p<0.001); and complicated 24 (20%) of fatalities. Positive HIV antibody status was more frequent in cases with diarrhoea at admission (23%) than those without (15%, Χ2 = 12.0 p = 0.001) but did not increase the risk of death in diarrhoea cases. Conclusion Children with SAM complicated by diarrhoea had a higher risk of death than those who did not have diarrhoea during their hospital stay. Further operational and clinical research is needed to reduce mortality in children with SAM in the given setting. PMID:22675542

  19. Relationship between Chinese medicine pattern types, clinical severity, and prognosis in patients with acute cerebral infarct.

    PubMed

    Jhong, Mao-chi; Tang, Nou-Ying; Liu, Chung-Hsiang; Huang, Wei-Hsih; Hsu, Yi-Ting; Liu, Yen-Liang; Li, Tsai-Chung; Hsieh, Ching-Liang

    2013-01-01

    We investigated the relationship between Chinese medicine pattern (CMP) types, their severity, and prognosis in patients (n = 187) with acute cerebral infarct (ACI). Six CMPs (wind, phlegm, fire-heat, blood stasis, qi deficiency, and yin deficiency and yang hyperactivity) were evaluated according to inspection, listening and smelling, inquiry, and palpitation. The severity and prognosis of each pattern type was determined according to the Glasgow Coma Scale (GCS), Modified Rankin Scale (MRS), National Institutes of Health Stroke Scale (NIHSS), Barthel Index (BI), and Functional Independence Measure (FIM), recorded at stroke onset and 12 weeks after stroke onset. The phlegm pattern (PP) patients displayed lower GCS, BI, and FIM scales scores, and higher MRS and NIHSS scales scores, than the nonphlegm pattern (N-PP) patients at, and 12 weeks after stroke onset, suggesting the clinical severity is greater and the prognosis is worse in PP patients with ACI than in non-PP patients with ACI. PMID:23906101

  20. Acute systemic hypotension after arteriovenous fistula construction in a patient with severe aortic stenosis.

    PubMed

    Mise, Naobumi; Uchida, Lisa; Tanaka, Mototsugu; Tanaka, Shinji; Nakajima, Hiroyoshi; Sugimoto, Tokuichiro

    2011-10-01

    We report the case of a 53-year-old hemodialysis patient with severe aortic stenosis, who developed acute systemic hypoperfusion after arteriovenous fistula (AVF) construction. He presented with hypotension and repeated syncope soon after distal radiocephalic AVF construction, and finally developed a respiratory arrest. His blood pressure and hemodynamics recovered promptly by sub-emergent aortic valve replacement surgery. In the present case, the heart with severe aortic stenosis could not increase cardiac output in response to the reduction in peripheral vascular resistance caused by the AVF. High-output heart failure, a relatively rare AVF-associated disorder, occurs with an excessive AVF flow, usually more than 3 L/min or 30% of cardiac output. However, heart failure may develop soon after construction of an AVF with a moderate blood flow if a patient's cardiac function is severely impaired. In addition, heart failure may improve with AVF preservation if the underlying heart disease is treatable. PMID:21725657

  1. Impact of Oxandrolone Treatment on Acute Outcomes After Severe Burn Injury

    PubMed Central

    Pham, Tam N.; Klein, Matthew B.; Gibran, Nicole S.; Arnoldo, Brett D.; Gamelli, Richard L.; Silver, Geoffrey M.; Jeschke, Marc G.; Finnerty, Celeste C.; Tompkins, Ronald G.; Herndon, David N.

    2013-01-01

    Pharmacologic modulation of hypermetabolism clearly benefits children with major burns, however, its role in adult burns remains to be defined. Oxandrolone appears to be a promising anabolic agent although few outcome data are as yet available. We examined whether early oxandrolone treatment in severely burned adults was associated with improved outcomes during acute hospitalization. We evaluated for potential associations between oxandrolone treatment and outcomes in a large cohort of severely burned adults in the context of a multicenter observational study. Patients were dichotomized with respect to oxandrolone treatment, defined as administration within 7 days after admission, with duration of at least 7 days. Acute hospitalization outcomes were compared with univariate and multivariate analyses. One hundred seventeen patients were included in this analysis. Mean patient age was 42.6 years (range, 18–86); 77% were male, with an average TBSA of 44.1%. Baseline and injury characteristics were similar among treatment and nontreatment cohorts. Oxandrolone treatment (N =59) did not impact length of stay but was associated with a lower mortality rate (P = .01) by univariate analysis. Oxandrolone treatment was independently associated with higher survival by adjusted analyses (P = .02). Examination of early oxandrolone treatment in this cohort of severely burned adults suggests that this therapy is safe and may be associated with improved survival. Further studies are necessary to define the exact mechanisms by which oxandrolone is beneficial during inpatient treatment. PMID:18849836

  2. Effect of nitric oxide inhalation on gas exchange in acute severe pneumonia.

    PubMed

    Gómez, Federico P; Amado, Veronica M; Roca, Josep; Torres, Antoni; Nicolas, Josep M; Rodriguez-Roisin, Robert; Barberà, Joan A

    2013-06-15

    Inhaled nitric oxide (NO) causes selective pulmonary vasodilatation and may improve gas exchange. The study was aimed to evaluate the acute effects of inhaled NO on pulmonary gas exchange in severe unilateral pneumonia, where hypoxemia results from increased intrapulmonary shunt. We studied 8 patients without preexisting lung disease (59±18 yr; 4M/4F) with early unilateral severe pneumonia and respiratory failure. Pulmonary and systemic hemodynamics and gas exchange, including ventilation-perfusion (V;A/Q;) distributions, were measured at baseline and while breathing 5 and 40 parts per million (ppm) of NO. Inhaled NO caused a dose-dependent fall in pulmonary vascular resistance (by 12% and 21%, with 5 and 40ppm, respectively; p<0.01, each) and improvement of PaO2 (by 25% and 23%; p<0.05, each), owing to the reduction of intrapulmonary shunt (by 23% and 27%; p<0.05, each), without changes in the amount of perfusion to low V;A/Q; ratio alveolar units. Patients with greater baseline intrapulmonary shunt exhibited greater improvement in arterial oxygenation (r(2)=0.55, p<0.05). We conclude that low doses of inhaled NO improve pulmonary gas exchange in acute severe pneumonia. PMID:23537586

  3. Applying Pharmacokinetics to Optimize Dosing of Anti-TNF Biologics in Acute Severe Ulcerative Colitis

    PubMed Central

    Rosen, Michael J.; Minar, Philip; Vinks, Alexander A.

    2015-01-01

    Background Acute severe ulcerative colitis (ASUC), the most aggressive presentation ulcerative colitis (UC), occurs in 15 percent of adults and children with UC. First line therapy with intravenous corticosteroids is ineffective in half of adults and one third of children. Therapeutic monoclonal antibodies against TNF (anti-TNF therapy) are emerging as a common treatment for ASUC due to their similar efficacy to calcineurin inhibitors and more favorable adverse effect profile. Aim To comprehensively review the evidence for anti-TNF therapy for ASUC in children and adults with regard to outcomes and pharmacokinetics. Methods PubMed and recent conference proceedings were searched using the terms “ulcerative colitis”, “acute severe ulcerative colitis”, “anti-TNF”, “pharmacokinetics”, and the generic names of specific anti-TNF agents. Results Outcomes after anti-TNF therapy for ASUC remain suboptimal with aboutone half of children and adults undergoing colectomy. While several randomized controlled trials have demonstrated the efficacy of anti-TNF therapy for ambulatory patients with moderate to severely active UC, patients in these studies were less ill than those with ASUC. Patients with ASUC may exhibit more rapid clearance of anti-TNF biologics due pharmacokinetic mechanisms influenced by disease severity. Conclusions Conventional weight-based dosing effective in patients with moderately to severely active UC, may not be equally effective in those with ASUC. Personalized anti-TNF dosing strategies that integratepatient factors and early measures of pharmacokinetics and response hold promise for ensuring sustained drug exposure and maximizing early mucosal healing in patients with ASUC. PMID:25809869

  4. Low risk of transmission of severe acute respiratory syndrome on airplanes: the Singapore experience.

    PubMed

    Wilder-Smith, Annelies; Paton, Nicholas I; Goh, Kee Tai

    2003-11-01

    The risk of transmission of severe acute respiratory syndrome (SARS) on airplanes is of major concern to the public and airline industry. We examined data from flights to Singapore with SARS patients on board in order to assess this risk. In-flight transmission occurred only in one of the three flights with symptomatic SARS patients on board. The incidence was estimated to be 1 out of 156 passengers. The risk of in-flight transmission of SARS appears to be far lower than that reported for influenza, but may be increased with superspreaders on board. PMID:14629772

  5. Tizanidine-induced acute severe cystitis in a female taking famotidine

    PubMed Central

    Poudel, Resham Raj; Kafle, Nisha Kusum

    2015-01-01

    Cystitis is a possible adverse drug reaction associated with the use of tizanidine. Such cases have been rarely reported in literature because of the difficulty in establishing the causality. However, from a pharmacovigilance point of view, it is better to report such cases of a possible association between a drug’s use and potential adverse drug reactions. We report a case of a 26-year-old Asian female on famotidine who presented with acute severe urinary burning after taking tizanidine. PMID:26251632

  6. Managing severe acute respiratory syndrome (SARS) intellectual property rights: the possible role of patent pooling.

    PubMed Central

    Simon, James H. M.; Claassen, Eric; Correa, Carmen E.; Osterhaus, Albert D. M. E.

    2005-01-01

    Patent applications that incorporate the genomic sequence of the severe acute respiratory syndrome (SARS) coronavirus, have been filed by a number of organizations. This is likely to result in a fragmentation of intellectual property (IP) rights which in turn may adversely affect the development of products, such as vaccines, to combat SARS. Placing these patent rights into a patent pool to be licensed on a non-exclusive basis may circumvent these difficulties and set a key precedent for the use of this form of mechanism in other areas of health care, leading to benefits to public health. PMID:16211163

  7. Longitudinal Analysis of Severe Acute Respiratory Syndrome (SARS) Coronavirus-Specific Antibody in SARS Patients

    PubMed Central

    Chang, Shan-Chwen; Wang, Jann-Tay; Huang, Li-Min; Chen, Yee-Chun; Fang, Chi-Tai; Sheng, Wang-Huei; Wang, Jiun-Ling; Yu, Chong-Jen; Yang, Pan-Chyr

    2005-01-01

    The serum antibodies to severe acute respiratory syndrome (SARS) coronavirus of 18 SARS patients were checked at 1 month and every 3 months after disease onset. All of them except one, who missed blood sampling at 1 month, tested positive for the immunoglobulin G (IgG) antibody at 1 month. Fifteen out of 17 tested positive for the IgM antibody at 1 month. The serum IgM antibody of most patients became undetectable within 6 months after the onset of SARS. The IgG antibody of all 17 patients, whose serum was checked 1 year after disease onset, remained positive. PMID:16339072

  8. Concepts in hypoxia reborn.

    PubMed

    Martin, Daniel S; Khosravi, Maryam; Grocott, Mike Pw; Mythen, Michael G

    2010-01-01

    The human fetus develops in a profoundly hypoxic environment. Thus, the foundations of our physiology are built in the most hypoxic conditions that we are ever likely to experience: the womb. This magnitude of exposure to hypoxia in utero is rarely experienced in adult life, with few exceptions, including severe pathophysiology in critical illness and environmental hypobaric hypoxia at high altitude. Indeed, the lowest recorded levels of arterial oxygen in adult humans are similar to those of a fetus and were recorded just below the highest attainable elevation on the Earth's surface: the summit of Mount Everest. We propose that the hypoxic intrauterine environment exerts a profound effect on human tolerance to hypoxia. Cellular mechanisms that facilitate fetal well-being may be amenable to manipulation in adults to promote survival advantage in severe hypoxemic stress. Many of these mechanisms act to modify the process of oxygen consumption rather than oxygen delivery in order to maintain adequate tissue oxygenation. The successful activation of such processes may provide a new chapter in the clinical management of hypoxemia. Thus, strategies employed to endure the relative hypoxia in utero may provide insights for the management of severe hypoxemia in adult life and ventures to high altitude may yield clues to the means by which to investigate those strategies. PMID:20727228

  9. Concepts in hypoxia reborn

    PubMed Central

    2010-01-01

    The human fetus develops in a profoundly hypoxic environment. Thus, the foundations of our physiology are built in the most hypoxic conditions that we are ever likely to experience: the womb. This magnitude of exposure to hypoxia in utero is rarely experienced in adult life, with few exceptions, including severe pathophysiology in critical illness and environmental hypobaric hypoxia at high altitude. Indeed, the lowest recorded levels of arterial oxygen in adult humans are similar to those of a fetus and were recorded just below the highest attainable elevation on the Earth's surface: the summit of Mount Everest. We propose that the hypoxic intrauterine environment exerts a profound effect on human tolerance to hypoxia. Cellular mechanisms that facilitate fetal well-being may be amenable to manipulation in adults to promote survival advantage in severe hypoxemic stress. Many of these mechanisms act to modify the process of oxygen consumption rather than oxygen delivery in order to maintain adequate tissue oxygenation. The successful activation of such processes may provide a new chapter in the clinical management of hypoxemia. Thus, strategies employed to endure the relative hypoxia in utero may provide insights for the management of severe hypoxemia in adult life and ventures to high altitude may yield clues to the means by which to investigate those strategies. PMID:20727228

  10. FDG uptake, a surrogate of tumour hypoxia?

    PubMed Central

    Van de Wiele, Christophe

    2008-01-01

    Introduction Tumour hyperglycolysis is driven by activation of hypoxia-inducible factor-1 (HIF-1) through tumour hypoxia. Accordingly, the degree of 2-fluro-2-deoxy-d-glucose (FDG) uptake by tumours might indirectly reflect the level of hypoxia, obviating the need for more specific radiopharmaceuticals for hypoxia imaging. Discussion In this paper, available data on the relationship between hypoxia and FDG uptake by tumour tissue in vitro and in vivo are reviewed. In pre-clinical in vitro studies, acute hypoxia was consistently shown to increase FDG uptake by normal and tumour cells within a couple of hours after onset with mobilisation or modification of glucose transporters optimising glucose uptake, followed by a delayed response with increased rates of transcription of GLUT mRNA. In pre-clinical imaging studies on chronic hypoxia that compared FDG uptake by tumours grown in rat or mice to uptake by FMISO, the pattern of normoxic and hypoxic regions within the human tumour xenografts, as imaged by FMISO, largely correlated with glucose metabolism although minor locoregional differences could not be excluded. In the clinical setting, data are limited and discordant. Conclusion Further evaluation of FDG uptake by various tumour types in relation to intrinsic and bioreductive markers of hypoxia and response to radiotherapy or hypoxia-dependent drugs is needed to fully assess its application as a marker of hypoxia in the clinical setting. PMID:18509637

  11. [CLINICAL AND LABORATORY FEATURES OF ACUTE PANCREATITIS BILIARY ETIOLOGY COURSE IN PATIENTS WITH DIABETES MELLITUS].

    PubMed

    Godlevskiy, A I; Savolyuk, S I; Tomashevskiy, Ya V

    2015-07-01

    The dynamics of cytopathic hypoxia markers in patients with acute pancreatitis (AP) biliary etiology (BE), depending on the presence of concomitant diabetes mellitus (DM), which is an independent factor of premorbid severity increase and increase in the degree of operational and anesthetic risk. Markers of cytopathic hypoxia use as methods for early diagnosis of acute liver failure (ALF) and monitoring the effectiveness of its correction promising. In terms of cytopathic hypoxia may be at the stage of laboratory diagnostics to distinguish between destructive and non-destructive forms APBE, and for markers of endothelial dysfunction--destructive forms on the area and depth of destruction of the pancreas. PMID:26591209

  12. Intestinal hypoperfusion contributes to gut barrier failure in severe acute pancreatitis.

    PubMed

    Rahman, Sakhawat H; Ammori, Basil J; Holmfield, John; Larvin, Michael; McMahon, Michael J

    2003-01-01

    Intestinal barrier failure and subsequent bacterial translocation have been implicated in the development of organ dysfunction and septic complications associated with severe acute pancreatitis. Splanchnic hypoperfusion and ischemia/reperfusion injury have been postulated as a cause of increased intestinal permeability. The urinary concentration of intestinal fatty acid binding protein (IFABP) has been shown to be a sensitive marker of intestinal ischemia, with increased levels being associated with ischemia/reperfusion. The aim of the current study was to assess the relationship between excretion of IFABP in urine, gut mucosal barrier failure (intestinal hyperpermeability and systemic exposure to endotoxemia), and clinical severity. Patients with a clinical and biochemical diagnosis of acute pancreatitis were studied within 72 hours of onset of pain. Polyethylene glycol probes of 3350 kDa and 400 kDa were administered enterally, and the ratio of the percentage of retrieval of each probe after renal excretion was used as a measure of intestinal macromolecular permeability. Collected urine was also used to determine the IFABP concentration (IFABP-c) and total IFABP (IFABP-t) excreted over the 24-hour period, using an enzyme-linked immunosorbent assay technique. The systemic inflammatory response was estimated from peak 0 to 72-hour plasma C-reactive protein levels, and systemic exposure to endotoxins was measured using serum IgM endotoxin cytoplasmic antibody (EndoCAb) levels. The severity of the attack was assessed on the basis of the Atlanta criteria. Sixty-one patients with acute pancreatitis (severe in 19) and 12 healthy control subjects were studied. Compared to mild attacks, severe attacks were associated with significantly higher urinary IFABP-c (median 1092 pg/ml vs. 84 pg/ml; P < 0.001) and IFABP-t (median 1.14 microg vs. 0.21 microg; P = 0.003). Furthermore, the control group had significantly lower IFABP-c (median 37 pg/ml; P = 0.029) and IFABP-t (median

  13. A prospective, randomized trial of BiPAP in severe acute congestive heart failure.

    PubMed

    Levitt, M A

    2001-11-01

    Noninvasive positive pressure ventilation has been found to be efficacious in the setting of acute respiratory failure, specifically in chronic obstructive pulmonary disease exacerbations. Its use in congestive heart failure (CHF) is less well established. Additionally, it has been reported that there is an increase in acute myocardial infarction (AMI) rate with the use of bilevel positive pressure ventilation (BiPAP) in CHF patients. This study examined whether BiPAP decreases the intubation rate or improves cardiopulmonary parameters in severe CHF patients compared to high flow O(2) by mask (MASK), and whether there is an increase in AMI rate with the use of BiPAP. A prospective, randomized clinical trial at a county hospital teaching Emergency Department was conducted by enrolling 38 patients who were in severe CHF. Patients were randomized to receive either BiPAP or MASK in addition to adjunct therapy. Age and gender were not different between the groups. Heart rate, systolic blood pressure, diastolic blood pressure, respiratory rate, and pulse oximetry all showed no significant difference in change over time between groups, but there was a significant change over time within groups. Arterial pH, pCO(2), and pO(2) also showed no significant difference in change over time between groups, but there was a significant change over time within groups. The intubation rate for BiPAP was 23.8% (5) vs. MASK at 41.2% (7). The AMI rate was 19% (4) in the BiPAP group and 29.4% (5) in the MASK group. No true differences were detected between groups for increased oxygenation or a reduction in intubation rate. An increase in AMI rate with BiPAP was not found in this study as previously reported. This study provides support for a larger clinical trial assessing the safety and efficacy of BiPAP in acute CHF. PMID:11728761

  14. Association between glucose-regulated protein and neutrophil apoptosis in severe acute pancreatitis

    PubMed Central

    Xu, Lan-Tao; Xu, He-Ling; Fu, Ming-Sheng

    2015-01-01

    Objective: This study aimed to investigate the role of glucose regulated protein 78 (GRP-78) in the apoptosis of neutrophils in rats with severe acute pancreatitis. Methods: A total of 54 SD male rats were randomly assigned into 2 groups: sham group (n=24) and pancreatitis group (n=30). Severe acute pancreatitis was induced by retrograde cholangiopancreatography injection of sodium taurocholate. Rats were sacrified at 3 h, 6 h and 12 h after injection. In control group, rats received laparotomy, but the pancreates remained intact. The serum amylase was detected at different time points, and flow cytometry was done to detect the apoptosis of neutrophils. Proteins were extracted from neutrophils and subjected to detection of GRP78 and Mcl-1 expression by Western blot assay. HE staining was performed for pathological scoring of the pancreas. Results: The serum amylase in pancreatitis group increased markedly when compared with control group (P<0.01). In SAP group, the serum amylase increased gradually over time (P<0.01). HE staining showed a lot of inflammatory cells and infiltration of red blood cells and the apoptosis rate of neutrophils reduced gradually (P<0.01). Western blot assay showed the protein expression of GRP-78 and Mcl-1 increased in neutrophils over time. Conclusion: In rats with SAP, the apoptosis rate of neutrophils reduced over time, which may be associated to the stress induced expression of GRP78 and subsequent activation of Mcl-1 resulting in suppression of neutrphil apoptosis over time. PMID:26464680

  15. Inhaled and intravenous treatment in acute severe and life-threatening asthma.

    PubMed

    Sellers, W F S

    2013-02-01

    Management of life-threatening acute severe asthma in children and adults may require anaesthetic and intensive care. The inhaled route for drug delivery is not appropriate when only small respiratory gas volumes are shifted; the i.v. route may be associated with greater side-effects. Magnesium sulphate i.v. has a place in acute asthma management because it is a mild bronchodilator, and has a stabilizing effect on the atria which may attenuate tachycardia occurring after inhaled and i.v. salbutamol. If intubation and ventilation are required, a reduction in bronchoconstriction by any means before and during these procedures should reduce morbidity. This narrative review aims to show strengths and weakness of the evidence, present controversies, and forward opinions of the author. The review contains a practical guide to the setting up, use and efficiency of nebulizers, metered dose inhalers, and spacers (chambers). It also presents a commonsense approach to the management of severe asthmatics in whom delay in bronchodilatation would cause clinical deterioration. When self-inhaled agents have had no effect, i.v. drugs may help avoid intubation and ventilation. The review includes suggestions for the use of inhaled anaesthetics, anaesthetic induction, and brief notes on subsequent ventilation of the lungs. PMID:23234642

  16. Recent developments in anti-severe acute respiratory syndrome coronavirus chemotherapy

    PubMed Central

    Barnard, Dale L; Kumaki, Yohichi

    2011-01-01

    Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in early 2003 to cause a very severe acute respiratory syndrome, which eventually resulted in a 10% case-fatality rate. Owing to excellent public health measures that isolated focus cases and their contacts, and the use of supportive therapies, the epidemic was suppressed to the point that further cases have not appeared since 2005. However, despite intensive research since then (over 3500 publications), it remains an untreatable disease. The potential for re-emergence of the SARS-CoV or a similar virus with unknown but potentially serious consequences remains high. This is due in part to the extreme genetic variability of RNA viruses such as the coronaviruses, the many animal reservoirs that seem to be able host the SARS-CoV in which reassortment or recombination events could occur and the ability coronaviruses have to transmit relatively rapidly from species to species in a short period of time. Thus, it seems prudent to continue to explore and develop antiviral chemotherapies to treat SARS-CoV infections. To this end, the various efficacious anti-SARS-CoV therapies recently published from 2007 to 2010 are reviewed in this article. In addition, compounds that have been tested in various animal models and were found to reduce virus lung titers and/or were protective against death in lethal models of disease, or otherwise have been shown to ameliorate the effects of viral infection, are also reported. PMID:21765859

  17. Acute phase reactants in Sudanese children with severe protein-energy malnutrition*

    PubMed Central

    Suliman, Omer S. M.; Salih, Mustafa A. M.; Karrar, Zein A.; Mohammed, Abdelrahim O.; Helsing, Chrestover

    2011-01-01

    The pre-dietary rehabilitation levels of acute phase proteins (APP) namely, alpha-1-antitrypsin (AAT), orosomucoid (ORO), haptoglobin (HAP), fibrinogen (FIB) and C-reactive protein (CRP) in the plasma of Sudanese children with severe protein energy malnutrition (PEM) were compared with those of normal controls, and with the levels after dietary rehabilitation. Eighty one children were included in the study; 49 with severe PEM (23 with marasmus, 17 with marasmic-kwashiorkor and 9 with kwashiorkor), 13 with tuberculosis (TB) and 19 healthy children as controls. The study showed a high incidence of infections, especially acute respiratory infection (ARI), diarrhoeal diseases and intestinal parasites in the malnourished children. The mean plasma level of albumin was significantly lower in the malnourished children compared to controls (P<0.001), with kwashiorkor children showing the lowest mean level. This hypoalbuminaemia was significantly associated with the presence of ARI and intestinal parasites. The mean plasma levels of the APP, except FIB, were significantly higher in malnourished children than in controls, with higher levels associated with ARI and the presence of fever. Malnourished children with TB had significantly higher mean levels of the APP (AAT, HAP, FIB, CRP) compared to those without TB. The mean levels of HAP and AAT were significantly lower in the presence of diarrhoea, suggesting their loss in the stool. The mean levels of the APP after two weeks dietary rehabilitation and antimicrobial treatment showed a significant drop in only two of the APP, namely CRP, ORO, while FIB showed a significant rise.

  18. Interventional Treatment of Abdominal Compartment Syndrome during Severe Acute Pancreatitis: Current Status and Historical Perspective

    PubMed Central

    Radenkovic, Dejan V.; Johnson, Colin D.; Milic, Natasa; Gregoric, Pavle; Ivancevic, Nenad; Bezmarevic, Mihailo; Bilanovic, Dragoljub; Cijan, Vladimir; Antic, Andrija; Bajec, Djordje

    2016-01-01

    Abdominal compartment syndrome (ACS) in patients with severe acute pancreatitis (SAP) is a marker of severe disease. It occurs as combination of inflammation of retroperitoneum, visceral edema, ascites, acute peripancreatic fluid collections, paralytic ileus, and aggressive fluid resuscitation. The frequency of ACS in SAP may be rising due to more aggressive fluid resuscitation, a trend towards conservative treatment, and attempts to use a minimally invasive approach. There remains uncertainty about the most appropriate surgical technique for the treatment of ACS in SAP. Some unresolved questions remain including medical treatment, indications, timing, and interventional techniques. This review will focus on interventional treatment of this serious condition. First line therapy is conservative treatment aiming to decrease IAP and to restore organ dysfunction. If nonoperative measures are not effective, early abdominal decompression is mandatory. Midline laparostomy seems to be method of choice. Since it carries significant morbidity we need randomized studies to establish firm advantages over other described techniques. After ACS resolves efforts should be made to achieve early primary fascia closure. Additional data are necessary to resolve uncertainties regarding ideal timing and indication for operative treatment. PMID:26839539

  19. Applying a low-flow CO2 removal device in severe acute hypercapnic respiratory failure.

    PubMed

    Sharma, Ajay S; Weerwind, Patrick W; Strauch, Uli; van Belle, Arne; Maessen, Jos G; Wouters, Emiel F M

    2016-03-01

    A novel and portable extracorporeal CO2-removal device was evaluated to provide additional gas transfer, auxiliary to standard therapy in severe acute hypercapnic respiratory failure. A dual-lumen catheter was inserted percutaneously in five subjects (mean age 55 ± 0.4 years) and, subsequently, connected to the CO2-removal device. The median duration on support was 45 hours (interquartile range 26-156), with a blood flow rate of approximately 500 mL/min. The mean PaCO2 decreased from 95.8 ± 21.9 mmHg to 63.9 ± 19.6 mmHg with the pH improving from 7.11 ± 0.1 to 7.26 ± 0.1 in the initial 4 hours of support. Three subjects were directly weaned from the CO2-removal device and mechanical ventilation, one subject was converted to ECMO and one subject died following withdrawal of support. No systemic bleeding or device complications were observed. Low-flow CO2 removal adjuvant to standard therapy was effective in steadily removing CO2, limiting the progression of acidosis in subjects with severe acute hypercapnic respiratory failure. PMID:26040584

  20. Interventional Treatment of Abdominal Compartment Syndrome during Severe Acute Pancreatitis: Current Status and Historical Perspective.

    PubMed

    Radenkovic, Dejan V; Johnson, Colin D; Milic, Natasa; Gregoric, Pavle; Ivancevic, Nenad; Bezmarevic, Mihailo; Bilanovic, Dragoljub; Cijan, Vladimir; Antic, Andrija; Bajec, Djordje

    2016-01-01

    Abdominal compartment syndrome (ACS) in patients with severe acute pancreatitis (SAP) is a marker of severe disease. It occurs as combination of inflammation of retroperitoneum, visceral edema, ascites, acute peripancreatic fluid collections, paralytic ileus, and aggressive fluid resuscitation. The frequency of ACS in SAP may be rising due to more aggressive fluid resuscitation, a trend towards conservative treatment, and attempts to use a minimally invasive approach. There remains uncertainty about the most appropriate surgical technique for the treatment of ACS in SAP. Some unresolved questions remain including medical treatment, indications, timing, and interventional techniques. This review will focus on interventional treatment of this serious condition. First line therapy is conservative treatment aiming to decrease IAP and to restore organ dysfunction. If nonoperative measures are not effective, early abdominal decompression is mandatory. Midline laparostomy seems to be method of choice. Since it carries significant morbidity we need randomized studies to establish firm advantages over other described techniques. After ACS resolves efforts should be made to achieve early primary fascia closure. Additional data are necessary to resolve uncertainties regarding ideal timing and indication for operative treatment. PMID:26839539

  1. Incidence and severity of reported acute sports injuries in 35 sports using insurance registry data.

    PubMed

    Åman, M; Forssblad, M; Henriksson-Larsén, K

    2016-04-01

    Acute injuries in sport are still a problem where limited knowledge of incidence and severity in different sports at national level exists. In Sweden, 80% of the sports federations have their mandatory injury insurance for all athletes in the same insurance company and injury data are systematically kept in a national database. The aim of the study was to identify high-risk sports with respect to incidence of acute and severe injuries in 35 sports reported to the database. The number and incidences of injuries as well as injuries leading to permanent medical impairment (PMI) were calculated during 2008-2011. Each year approximately 12,000 injuries and 1,162,660 licensed athletes were eligible for analysis. Eighty-five percent of the injuries were reported in football, ice hockey, floorball, and handball. The highest injury incidence as well as PMI was in motorcycle, handball, skating, and ice hockey. Females had higher risk of a PMI compared with males in automobile sport, handball, floorball, and football. High-risk sports with numerous injuries and high incidence of PMI injuries were motorcycle, handball, ice hockey, football, floorball, and automobile sports. Thus, these sports ought to be the target of preventive actions at national level. PMID:25850826

  2. Detection of airborne severe acute respiratory syndrome (SARS) coronavirus and environmental contamination in SARS outbreak units.

    PubMed

    Booth, Timothy F; Kournikakis, Bill; Bastien, Nathalie; Ho, Jim; Kobasa, Darwyn; Stadnyk, Laurie; Li, Yan; Spence, Mel; Paton, Shirley; Henry, Bonnie; Mederski, Barbara; White, Diane; Low, Donald E; McGeer, Allison; Simor, Andrew; Vearncombe, Mary; Downey, James; Jamieson, Frances B; Tang, Patrick; Plummer, Frank

    2005-05-01

    Severe acute respiratory syndrome (SARS) is characterized by a risk of nosocomial transmission; however, the risk of airborne transmission of SARS is unknown. During the Toronto outbreaks of SARS, we investigated environmental contamination in SARS units, by employing novel air sampling and conventional surface swabbing. Two polymerase chain reaction (PCR)-positive air samples were obtained from a room occupied by a patient with SARS, indicating the presence of the virus in the air of the room. In addition, several PCR-positive swab samples were recovered from frequently touched surfaces in rooms occupied by patients with SARS (a bed table and a television remote control) and in a nurses' station used by staff (a medication refrigerator door). These data provide the first experimental confirmation of viral aerosol generation by a patient with SARS, indicating the possibility of airborne droplet transmission, which emphasizes the need for adequate respiratory protection, as well as for strict surface hygiene practices. PMID:15809906

  3. Viruses as Sole Causative Agents of Severe Acute Respiratory Tract Infections in Children

    PubMed Central

    Moesker, Fleur M.; van Kampen, Jeroen J. A.; van Rossum, Annemarie M. C.; de Hoog, Matthijs; Koopmans, Marion P. G.; Osterhaus, Albert D. M. E.; Fraaij, Pieter L. A.

    2016-01-01

    Background Respiratory syncytial virus (RSV) and influenza A viruses are known to cause severe acute respiratory tract infections (SARIs) in children. For other viruses like human rhinoviruses (HRVs) this is less well established. Viral or bacterial co-infections are often considered essential for severe manifestations of these virus infections. Objective The study aims at identifying viruses that may cause SARI in children in the absence of viral and bacterial co-infections, at identifying disease characteristics associated with these single virus infections, and at identifying a possible correlation between viral loads and disease severities. Study Design Between April 2007 and March 2012, we identified children (<18 year) with or without a medical history, admitted to our paediatric intensive care unit (PICU) with SARI or to the medium care (MC) with an acute respiratory tract infection (ARTI) (controls). Data were extracted from the clinical and laboratory databases of our tertiary care paediatric hospital. Patient specimens were tested for fifteen respiratory viruses with real-time reverse transcriptase PCR assays and we selected patients with a single virus infection only. Typical bacterial co-infections were considered unlikely to have contributed to the PICU or MC admission based on C-reactive protein-levels or bacteriological test results if performed. Results We identified 44 patients admitted to PICU with SARI and 40 patients admitted to MC with ARTI. Twelve viruses were associated with SARI, ten of which were also associated with ARTI in the absence of typical bacterial and viral co-infections, with RSV and HRV being the most frequent causes. Viral loads were not different between PICU-SARI patients and MC-ARTI patients. Conclusion Both SARI and ARTI may be caused by single viral pathogens in previously healthy children as well as in children with a medical history. No relationship between viral load and disease severity was identified. PMID:26964038

  4. Adenosine receptors mediate the hypoxic ventilatory response but not the hypoxic metabolic response in the naked mole rat during acute hypoxia.

    PubMed

    Pamenter, Matthew E; Dzal, Yvonne A; Milsom, William K

    2015-02-01

    Naked mole rats are the most hypoxia-tolerant mammals identified; however, the mechanisms underlying this tolerance are poorly understood. Using whole-animal plethysmography and open-flow respirometry, we examined the hypoxic metabolic response (HMR), hypoxic ventilatory response (HVR) and hypoxic thermal response in awake, freely behaving naked mole rats exposed to 7% O₂ for 1 h. Metabolic rate and ventilation each reversibly decreased 70% in hypoxia (from 39.6 ± 2.9 to 12.1 ± 0.3 ml O₂ min(-1) kg(-1), and 1412 ± 244 to 417 ± 62 ml min(-1) kg(-1), respectively; p < 0.05), whereas body temperature was unchanged and animals remained awake and active. Subcutaneous injection of the general adenosine receptor antagonist aminophylline (AMP; 100 mg kg(-1), in saline), but not control saline injections, prevented the HVR but had no effect on the HMR. As a result, AMP-treated naked mole rats exhibited extreme hyperventilation in hypoxia. These animals were also less tolerant to hypoxia, and in some cases hypoxia was lethal following AMP injection. We conclude that in naked mole rats (i) hypoxia tolerance is partially dependent on profound hypoxic metabolic and ventilatory responses, which are equal in magnitude but occur independently of thermal changes in hypoxia, and (ii) adenosine receptors mediate the HVR but not the HMR. PMID:25520355

  5. Adenosine receptors mediate the hypoxic ventilatory response but not the hypoxic metabolic response in the naked mole rat during acute hypoxia

    PubMed Central

    Pamenter, Matthew E.; Dzal, Yvonne A.; Milsom, William K.

    2015-01-01

    Naked mole rats are the most hypoxia-tolerant mammals identified; however, the mechanisms underlying this tolerance are poorly understood. Using whole-animal plethysmography and open-flow respirometry, we examined the hypoxic metabolic response (HMR), hypoxic ventilatory response (HVR) and hypoxic thermal response in awake, freely behaving naked mole rats exposed to 7% O2 for 1 h. Metabolic rate and ventilation each reversibly decreased 70% in hypoxia (from 39.6 ± 2.9 to 12.1 ± 0.3 ml O2 min−1 kg−1, and 1412 ± 244 to 417 ± 62 ml min−1 kg−1, respectively; p < 0.05), whereas body temperature was unchanged and animals remained awake and active. Subcutaneous injection of the general adenosine receptor antagonist aminophylline (AMP; 100 mg kg−1, in saline), but not control saline injections, prevented the HVR but had no effect on the HMR. As a result, AMP-treated naked mole rats exhibited extreme hyperventilation in hypoxia. These animals were also less tolerant to hypoxia, and in some cases hypoxia was lethal following AMP injection. We conclude that in naked mole rats (i) hypoxia tolerance is partially dependent on profound hypoxic metabolic and ventilatory responses, which are equal in magnitude but occur independently of thermal changes in hypoxia, and (ii) adenosine receptors mediate the HVR but not the HMR. PMID:25520355

  6. Inhibition of SOCs Attenuates Acute Lung Injury Induced by Severe Acute Pancreatitis in Rats and PMVECs Injury Induced by Lipopolysaccharide.

    PubMed

    Wang, Guanyu; Zhang, Jingwen; Xu, Caiming; Han, Xiao; Gao, Yanyan; Chen, Hailong

    2016-06-01

    Acute lung injury (ALI) is a critical complication of the severe acute pancreatitis (SAP), characterized by increased pulmonary permeability with high mortality. Pulmonary microvascular endothelial cells (PMVECs) injury and apoptosis play a key role in ALI. Previous studies indicated that store-operated calcium entry (SOCE) could regulate a variety of cellular processes. The present study was to investigate the effects of SOCE inhibition on ALI induced by SAP in Sprague-Dawley rats, and PMVECs injury induced by lipopolysaccharide (LPS). Rat model of SAP-associated ALI were established by the retrograde infusion of sodium deoxycholate. Serum levels of amylase, TNF-α, and IL-6, histological changes, water content of the lung, oxygenation index, and ultrastructural changes of PMVECs were examined in ALI rats with or without store-operated Ca(2+) channels (SOCs) pharmacological inhibitor (2-aminoethoxydiphenyl borate, 2-APB) pretreatment. For in vitro studies, PMVECs were transiently transfected with or without small interfering RNA (siRNA) against calcium release-activated calcium channel protein1 (Orai1) and stromal interaction molecule1 (STIM1), the two main molecular constituents of SOCs, then exposed to LPS. The viability of PMVECs was determined. The expression of STIM1, Orai1, Bax, and caspase3, both in lung tissue and in PMVECs, were assessed by quantitative real-time PCR and western blot. Administration of sodium deoxycholate upregulated the expression of SOCs proteins in lung tissue. Similarly, the SOCs proteins were increased in PMVECs induced by LPS. 2-APB reduced the serum levels of amylase, TNF-α, and IL-6, and attenuated lung water content and histological findings. In addition, the decreased oxygenation index and ultrastructural damage in PMVECs associated with SAP were ameliorated after administration of 2-APB. Knockdown of STIM1 and Orai1 inhibited LPS-induced PMVECs death. Furthermore, blockade of SOCE significantly suppressed Orai1, STIM1, Bax

  7. Hypoxia and Dysregulated Angiogenesis in Kidney Disease

    PubMed Central

    Tanaka, Shinji; Tanaka, Tetsuhiro; Nangaku, Masaomi

    2015-01-01

    Background Accumulating evidence has demonstrated that renal hypoxia has a crucial role in the pathogenesis of acute kidney injury (AKI), chronic kidney disease (CKD), and AKI-to-CKD transition, ultimately culminating in end-stage kidney disease. Renal hypoxia in progressive CKD is intricately linked to persisting capillary loss, which is mainly due to dysregulated angiogenesis. Summary In CKD, hypoxia-inducible factor (HIF) accumulates in the ischemic tubulointerstitium but fails to sufficiently stimulate angiogenic responses, partly because of blunted activation of HIF, which is best exemplified in diabetic kidney disease. In addition, vascular endothelial growth factor (VEGF) expression is downregulated, possibly because injured tubules are not able to express sufficient VEGF and inflammatory circumstances inhibit VEGF expression. The upregulation of antiangiogenic factors and the incompetence of endothelial progenitor cells (EPCs) may also play some roles in the inadequacy of capillary restoration. Administration of VEGF or angiopoietin-1 maintains peritubular capillaries in several kidney diseases; however, administration of a single angiogenic factor may lead to the formation of abnormal vessels and induce inflammation, resulting in worsening of hypoxia and tubulointerstitial fibrosis. HIF stabilization, which aims to achieve the formation of mature and stable vessels by inducing coordinated angiogenesis, is a promising strategy. Given that the effect of systemic HIF activation is highly context-dependent, further studies are needed to elucidate the precise roles of HIF in various kidney diseases. The adoptive transfer of EPCs or mesenchymal stem cells (MSCs) is a fascinating alternative strategy to restore the peritubular capillaries. Key Message Suppressed HIF activation and VEGF expression may be responsible for the dysregulated angiogenesis in progressive CKD. Administration of a single angiogenic factor can cause abnormal vessel formation and

  8. Effectiveness of Acute Phase Hybrid Assistive Limb Rehabilitation in Stroke Patients Classified by Paralysis Severity

    PubMed Central

    FUKUDA, Hiroyuki; SAMURA, Kazuhiro; HAMADA, Omi; SAITA, Kazuya; OGATA, Toshiyasu; SHIOTA, Etsuji; SANKAI, Yoshiyuki; INOUE, Tooru

    The purpose of the present study was to investigate the effectiveness of acute phase hybrid assistive limb (HAL) rehabilitation training for patients after stroke by measuring the difference in the severity of paralysis. Fifty-three acute stroke patients were enrolled in this prospective cohort study. HAL training was administered about twice per week, and the mean number of sessions was 3.9 ± 2.7. The walking training was performed on a treadmill with individually adjustable body weight support and speed and there was a 10-m walk test (10MWT) before and after each session. Assessment at baseline and at endpoint consisted of the Glasgow Coma Scale (GCS), Revised Hasegawa’s Dementia Scale (HDS-R), Brunnstrom stage (Brs), Functional Independence Measure (FIM), Barthel index (BI), and 10MWT. We measured these assessments at the first walking training session and at the end of the final training session without the HAL. To evaluate the feasibility of training with the HAL, the outcome measures of BI, FIM, and speed and number of steps of 10MWT were compared before and after training using a paired Wilcoxon’s signed-rank test in different Brs. Except for Brs IV, the Brs III or higher subgroups displayed significant amelioration in BI, and the Brs III subgroup displayed significant amelioration in FIM. The Brs V and VI subgroups displayed significant amelioration in 10-m walking speed and steps. In acute phase rehabilitation after stroke, it is thought that the HAL is more effective for patients with less lower-limb paralysis, such as Brs III or higher. PMID:26041627

  9. Urine Microscopy Is Associated with Severity and Worsening of Acute Kidney Injury in Hospitalized Patients

    PubMed Central

    Coca, Steven G.; Hall, Isaac E.; Iyanam, Umo; Koraishy, Madiha; Parikh, Chirag R.

    2010-01-01

    Background and objectives: Serum creatinine concentration at the time of nephrology consultation is not necessarily indicative of the severity of acute kidney injury (AKI). Although urine microscopy is useful to differentiate AKI, its role in predicting adverse clinical outcomes has not been well described. Design, setting, participants, & measurements: The relationship between urine microscopy findings at the time of nephrology consultation for AKI and clinical outcomes was evaluated prospectively. A urinary sediment scoring system was created on the basis of the number of renal tubular epithelial cells and granular casts. The primary outcome was worsening of AKI (progressing to higher AKI Network stage, dialysis, or death) during hospitalization. Results: Of 249 patients consulted for AKI, 197 had acute tubular necrosis or prerenal AKI and were included in the analysis. At consultation, 80 (40%) had stage 1, 53 (27%) had stage 2, and 66 (33%) had stage 3 AKI. The urinary sediment combined scores were lowest in those with stage 1 and highest in stage 3 AKI. Seventy-nine patients (40%) experienced worsening of AKI from the time of consultation. The urinary scoring system was significantly associated with increased risk of worsening AKI (adjusted relative risk: 7.3; 95% confidence interval: 4.5 to 9.7 for worsening with score of ≥3 versus score of 0) and was more predictive than AKI Network stage at the time of consultation. Conclusions: The urinary sediment score may be a useful tool to predict worsening of AKI due to either acute tubular necrosis or prerenal AKI during hospitalization. PMID:20089493

  10. Genetic Polymorphisms in the Dopamine Receptor 2 Predict Acute Pain Severity after Motor Vehicle Collision

    PubMed Central

    Qadri, Yawar J.; Bortsov, Andrey V.; Orrey, Danielle C.; Swor, Robert A.; Peak, David A.; Jones, Jeffrey S.; Rathlev, Niels K.; Lee, David C.; Domeier, Robert M.; Hendry, Phyllis L.; Mclean, Samuel A.

    2014-01-01

    Objectives: Dopaminergic signaling is implicated in nociceptive pathways. These effects are mediated largely through dopamine receptors and modulated in part by dopamine transporters. This study tests the hypothesis that genetic variants in the genes encoding dopamine receptor 2 (DRD2) and the dopamine active transporter (SLC6A3) influence acute pain severity after motor vehicle collision (MVC). Methods: European Americans presenting to the emergency department (ED) after MVC were recruited. Overall pain intensity in ED was assessed using a 0-10 numeric rating scale. DNA was extracted from blood samples and genotyping of single nucleotide polymorphisms (SNPs) in the DRD2 and SLC6A3 gene was performed. Results: A total of 948 patients completed evaluation. After correction for multiple comparisons, SNP rs6276 at DRD2 showed significant association with pain scores, with individuals with the A/A genotype reporting lower mean pain scores (5.3, 95% CI 5.1 to 5.5) than those with A/G (5.9, 95% CI 5.6 to 6.1) or G/G (5.7, 95%CI 5.2 to 6.2) genotypes (p=0.0027). Secondary analyses revealed an interaction between sex and DRD2 SNPs rs4586205 and rs4648318 on pain scores: females with two minor alleles had increased pain intensity, whereas males with two minor alleles had less pain than individuals with a major allele (interaction p=0.0019). Discussion: Genetic variants in DRD2 are associated with acute pain after a traumatic stressful event. These results suggest that dopaminergic agents may be useful for the treatment of individuals with acute post-traumatic pain as part of a multimodal opioid-sparing analgesic regimen. PMID:25370144

  11. Viral Infection in Adults with Severe Acute Respiratory Infection in Colombia

    PubMed Central

    Remolina, Yuly Andrea; Ulloa, María Mercedes; Vargas, Hernán; Díaz, Liliana; Gómez, Sandra Liliana; Saavedra, Alfredo; Sánchez, Edgar; Cortés, Jorge Alberto

    2015-01-01

    Objectives To identify the viral aetiology in adult patients with severe acute respiratory infection (SARI) admitted to sentinel surveillance institutions in Bogotá in 2012. Design A cross-sectional study was conducted in which microarray molecular techniques for viral identification were used on nasopharyngeal samples of adult patients submitted to the surveillance system, and further descriptions of clinical features and relevant clinical outcomes, such as mortality, need for critical care, use of mechanical ventilation and hospital stay, were obtained. Setting Respiratory infections requiring hospital admission in surveillance centres in Bogotá, Colombia. Participants Ninety-one adult patients with acute respiratory infection (55% were female). Measurements Viral identification, intensive care unit admission, hospital stay, and mortality. Results Viral identification was achieved for 63 patients (69.2%). Comorbidity was frequently identified and mainly involved chronic pulmonary disease or pregnancy. Influenza, Bocavirus and Adenovirus were identified in 30.8%, 28.6% and 18.7% of the cases, respectively. Admission to the intensive care unit occurred in 42.9% of the cases, while mechanical ventilation was required for 36.3%. The average hospital stay was 9.9 days, and mortality was 15.4%. Antibiotics were empirically used in 90.1% of patients. Conclusions The prevalence of viral aetiology of SARI in this study was high, with adverse clinical outcomes, intensive care requirements and high mortality. PMID:26576054

  12. [Severe Japanese Spotted Fever Complicated by Acute Respiratory Failure in Kobe City].

    PubMed

    Takiguchi, Junji; Okimura, Kenjiro; Ishii, Mariko; Okamura, Kayoko; Sakamoto, Hirokazu; Inamoto, Shinya; Ando, Shuji

    2016-03-01

    We report herein on a case of severe Japanese spotted fever complicated by acute respiratory failure in Kobe City. A 70-year-old female presenting with general malaise and systematic erythema was admitted to our hospital in June, 2013. From her history and physical examination, she was found to be suffering from scleroderma and mild interstitial pneumonia. From admission, the patient was noted to have a fever of 39 degrees C accompanied by relative bradycardia. Physical examination revealed a black eschar on her right leg, making us suspect rickettsial infection since Kobe City is not an area predisposed to Japanese spotted fever. Three days after admission, her condition worsened and treatment with minocycline and levofloxacin was initiated in accordance with the treatment protocol for Japanese spotted fever. The following day, the patient developed acute respiratory distress syndrome (ARDS) and was put on a respirator. She gradually recovered with the antibiotic treatment and was discharged from the hospital 23 days after admission. The diagnosis of Japanese spotted fever was confirmed by conducting a polymerase chain reaction test on the eschar. Japanese spotted fever is noted to occur in any place other than Kobe City. Late diagnoses may result in aggravated cases of Japanese spotted fever, with the possibility of developing ARDS as a complication. PMID:27197438

  13. Skeletal muscle vasodilation during systemic hypoxia in humans.

    PubMed

    Dinenno, Frank A

    2016-01-15

    In humans, the net effect of acute systemic hypoxia in quiescent skeletal muscle is vasodilation despite significant reflex increases in muscle sympathetic vasoconstrictor nerve activity. This vasodilation increases tissue perfusion and oxygen delivery to maintain tissue oxygen consumption. Although several mechanisms may be involved, we recently tested the roles of two endothelial-derived substances during conditions of sympathoadrenal blockade to isolate local vascular control mechanisms: nitric oxide (NO) and prostaglandins (PGs). Our findings indicate that 1) NO normally plays a role in regulating vascular tone during hypoxia independent of the PG pathway; 2) PGs do not normally contribute to vascular tone during hypoxia, however, they do affect vascular tone when NO is inhibited; 3) NO and PGs are not independently obligatory to observe hypoxic vasodilation when assessed as a response from rest to steady-state hypoxia; and 4) combined NO and PG inhibition abolishes hypoxic vasodilation in human skeletal muscle. When the stimulus is exacerbated via combined submaximal rhythmic exercise and systemic hypoxia to cause further red blood cell (RBC) deoxygenation, skeletal muscle blood flow is augmented compared with normoxic exercise via local dilator mechanisms to maintain oxygen delivery to active tissue. Data obtained in a follow-up study indicate that combined NO and PG inhibition during hypoxic exercise blunts augmented vasodilation and hyperemia compared with control (normoxic) conditions by ∼50%; however, in contrast to hypoxia alone, the response is not abolished, suggesting that other local substances are involved. Factors associated with greater RBC deoxygenation such as ATP release, or nitrite reduction to NO, or both likely play a role in regulating this response. PMID:26023228

  14. Aging, Tolerance to High Altitude, and Cardiorespiratory Response to Hypoxia.

    PubMed

    Richalet, Jean-Paul; Lhuissier, François J

    2015-06-01

    Richalet, Jean-Paul, and François J. Lhuissier. Aging, tolerance to high altitude, and cardiorespiratory response to hypoxia. High Alt Med Biol. 16:117-124, 2015.--It is generally accepted that aging is rather protective, at least at moderate altitude. Some anecdotal reports even mention successful ascent of peaks over 8000 m and even Everest by elderly people. However, very few studies have explored the influence of aging on tolerance to high altitude and prevalence of acute high altitude related diseases, taking into account all confounding factors such as speed of ascent, altitude reached, sex, training status, and chemo-responsiveness. Changes in physiological responses to hypoxia with aging were assessed through a cross-sectional 20-year study including 4675 subjects (2789 men, 1886 women; 14-85 yrs old) and a longitudinal study including 30 subjects explored at a mean 10.4-year interval. In men, ventilatory response to hypoxia increased, while desaturation was less pronounced with aging. Cardiac response to hypoxia was blunted with aging in both genders. Similar results were found in the longitudinal study, with a decrease in cardiac and an increase in ventilatory response to hypoxia with aging. These adaptive responses were less pronounced or absent in post-menopausal untrained women. In conclusion, in normal healthy and active subjects, aging has no deleterious effect on cardiac and ventilatory responses to hypoxia, at least up to the eighth decade. Aging is not a contraindication for high altitude, as far as no pathological condition interferes and physical fitness is compatible with the intensity of the expected physical demand of one's individual. Physiological evaluation through hypoxic exercise testing before going to high altitude is helpful to detect risk factors of severe high altitude-related diseases. PMID:25946570

  15. Comorbidity as a contributor to frequent severe acute exacerbation in COPD patients

    PubMed Central

    Jeong, Suk Hyeon; Lee, Hyun; Carriere, KC; Shin, Sun Hye; Moon, Seong Mi; Jeong, Byeong-Ho; Koh, Won-Jung; Park, Hye Yun

    2016-01-01

    Background Comorbidities have a serious impact on the frequent severe acute exacerbations (AEs) in patients with COPD. Previous studies have used the Charlson comorbidity index to represent a conglomerate of comorbidities; however, the respective contribution of each coexisting disease to the frequent severe AEs remains unclear. Methods A retrospective, observational study was performed in 77 COPD patients who experienced severe AE between January 2012 and December 2014 and had at least 1-year follow-up period from the date of admission for severe AE. We explored the incidence of frequent severe AEs (≥2 severe AEs during 1-year period) in these patients and investigated COPD-related factors and comorbidities as potential risk factors of these exacerbations. Results Out of 77 patients, 61 patients (79.2%) had at least one comorbidity. During a 1-year follow-up period, 29 patients (37.7%) experienced frequent severe AEs, approximately two-thirds (n=19) of which occurred within the first 90 days after admission. Compared with patients not experiencing frequent severe AEs, these patients were more likely to have poor lung function and receive home oxygen therapy and long-term oral steroids. In multiple logistic regression analysis, coexisting asthma (adjusted odds ratio [OR] =4.02, 95% confidence interval [CI] =1.30–12.46, P=0.016), home oxygen therapy (adjusted OR =9.39, 95% CI =1.60–55.30, P=0.013), and C-reactive protein (adjusted OR =1.09, 95% CI =1.01–1.19, P=0.036) were associated with frequent severe AEs. In addition, poor lung function, as measured by forced expiratory volume in 1 second (adjusted OR =0.16, 95% CI =0.04–0.70, P=0.015), was inversely associated with early (ie, within 90 days of admission) frequent severe AEs. Conclusion Based on our study, among COPD-related comorbidities, coexisting asthma has a significant impact on the frequent severe AEs in COPD patients. PMID:27536097

  16. Taiwan's traffic control bundle and the elimination of nosocomial severe acute respiratory syndrome among healthcare workers.

    PubMed

    Yen, M-Y; Lin, Y-E; Lee, C-H; Ho, M-S; Huang, F-Y; Chang, S-C; Liu, Y-C

    2011-04-01

    The traffic control bundle consists of procedures designed to help prevent epidemic nosocomial infection. We retrospectively studied the serial infection control measures to determine factors most effective in preventing nosocomial infections of healthcare workers (HCWs) during the 2003 Taiwanese severe acute respiratory syndrome (SARS) epidemic. Fever screening stations, triage of fever patients, separating SARS patients from other patients, separation of entrances and passageways between patients and HCWs, and increasing hand-washing facilities all demonstrated a protective effect for HCWs (univariate analysis; P<0.05). By multiple logistic regression: (i) checkpoint alcohol dispensers for glove-on hand rubbing between zones of risk, and (ii) fever screening at the fever screen station outside the emergency department, were the significant methods effectively minimising nosocomial SARS infection of HCWs (P<0.05). The traffic control bundle should be implemented in future epidemics as a tool to achieve strict infection control measures. PMID:21316802

  17. A case of γ-butyrolactone associated with severe withdrawal delirium and acute renal failure.

    PubMed

    Bhattacharya, Indrani S; Watson, Fiona; Bruce, Malcolm

    2011-01-01

    γ-Butyrolactone (GBL) is a popular drug of abuse which is easily available over the internet. Following a UK classification change to a class C drug in January 2010, internet supply has become difficult. Some of the effects have resulted in sourcing GBL from industrial solvents. We report a case of a 24-year-old man who was admitted for detoxification from GBL. He reported having sourced the GBL by diluting the contents of nail varnish remover pads with water. During his admission he developed a severe withdrawal delirium and acute renal failure. He required admission to the intensive care unit. Physicians and psychiatrists should be aware of toxic sources of GBL leading to renal failure and consider GBL in those presenting with agitation, psychosis or coma. PMID:21454980

  18. Severe acute interstitial nephritis after combination immune-checkpoint inhibitor therapy for metastatic melanoma.

    PubMed

    Murakami, Naoka; Borges, Thiago J; Yamashita, Michifumi; Riella, Leonardo V

    2016-06-01

    Immune-checkpoint inhibitors are emerging as revolutionary drugs for certain malignancies. However, blocking the co-inhibitory signals may lead to immune-related adverse events, mainly in the spectrum of autoimmune diseases including colitis, endocrinopathies and nephritis. Here, we report a case of a 75-year-old man with metastatic malignant melanoma treated with a combination of nivolumab (anti-PD1-antibody) and ipilimumab (anti-CTLA-4 antibody) who developed systemic rash along with severe acute tubulointerstitial nephritis after two doses of combination therapy. Kidney biopsy and peripheral blood immune profile revealed highly proliferative and cytotoxic T cell features. Herein, we discuss the pathophysiology and management of immune checkpoint blockade-related adverse events. PMID:27274826

  19. Spatial dynamics of an epidemic of severe acute respiratory syndrome in an urban area.

    PubMed Central

    Wang, Jinfeng; McMichael, Anthony J.; Meng, Bin; Becker, Niels G.; Han, Weiguo; Glass, Kathryn; Wu, Jilei; Liu, Xuhua; Liu, Jiyuan; Li, Xiaowen; Zheng, Xiaoying

    2006-01-01

    OBJECTIVE: To map risk of exposure to severe acute respiratory syndrome (SARS) in an urban area and assess the ability of traditional interventions to control dispersion of the disease. METHODS: Data on the Beijing SARS epidemic were used to map spatial clusters of identified contacts and to estimate transmission of SARS using a model with a time-dependent transmission rate. RESULTS: The estimated transmission rate decreased dramatically from 20 to 30 April 2003. The total number of cases in the epidemic in Beijing was estimated to be 2521. Hierarchical clustering revealed that risk-exposures were widespread, but clustered in a pattern that is distinctly related to the Beijing urban ring roads. CONCLUSION: Traditional control measures can be very effective at reducing transmission of SARS. Spatial patterns of risk-exposures can inform disease surveillance, prediction and control by identifying spatial target areas on which interventions should be focused. PMID:17242832

  20. Prospects for emerging infections in East and southeast Asia 10 years after severe acute respiratory syndrome.

    PubMed

    Horby, Peter W; Pfeiffer, Dirk; Oshitani, Hitoshi

    2013-06-01

    It is 10 years since severe acute respiratory syndrome (SARS) emerged, and East and Southeast Asia retain a reputation as a hot spot of emerging infectious diseases. The region is certainly a hot spot of socioeconomic and environmental change, and although some changes (e.g., urbanization and agricultural intensification) may reduce the probability of emerging infectious diseases, the effect of any individual emergence event may be increased by the greater concentration and connectivity of livestock, persons, and products. The region is now better able to detect and respond to emerging infectious diseases than it was a decade ago, but the tools and methods to produce sufficiently refined assessments of the risks of disease emergence are still lacking. Given the continued scale and pace of change in East and Southeast Asia, it is vital that capabilities for predicting, identifying, and controlling biologic threats do not stagnate as the memory of SARS fades. PMID:23738977

  1. Prospects for Emerging Infections in East and Southeast Asia 10 Years after Severe Acute Respiratory Syndrome

    PubMed Central

    Pfeiffer, Dirk; Oshitani, Hitoshi

    2013-01-01

    It is 10 years since severe acute respiratory syndrome (SARS) emerged, and East and Southeast Asia retain a reputation as a hot spot of emerging infectious diseases. The region is certainly a hot spot of socioeconomic and environmental change, and although some changes (e.g., urbanization and agricultural intensification) may reduce the probability of emerging infectious diseases, the effect of any individual emergence event may be increased by the greater concentration and connectivity of livestock, persons, and products. The region is now better able to detect and respond to emerging infectious diseases than it was a decade ago, but the tools and methods to produce sufficiently refined assessments of the risks of disease emergence are still lacking. Given the continued scale and pace of change in East and Southeast Asia, it is vital that capabilities for predicting, identifying, and controlling biologic threats do not stagnate as the memory of SARS fades. PMID:23738977

  2. New coronavirus outbreak. Lessons learned from the severe acute respiratory syndrome epidemic.

    PubMed

    Álvarez, E; Donado-Campos, J; Morilla, F

    2015-10-01

    System dynamics approach offers great potential for addressing how intervention policies can affect the spread of emerging infectious diseases in complex and highly networked systems. Here, we develop a model that explains the severe acute respiratory syndrome coronavirus (SARS-CoV) epidemic that occurred in Hong Kong in 2003. The dynamic model developed with system dynamics methodology included 23 variables (five states, four flows, eight auxiliary variables, six parameters), five differential equations and 12 algebraic equations. The parameters were optimized following an iterative process of simulation to fit the real data from the epidemics. Univariate and multivariate sensitivity analyses were performed to determine the reliability of the model. In addition, we discuss how further testing using this model can inform community interventions to reduce the risk in current and future outbreaks, such as the recently Middle East respiratory syndrome coronavirus (MERS-CoV) epidemic. PMID:25591619

  3. Protective Effect of Tetrandrine on Sodium Taurocholate-Induced Severe Acute Pancreatitis

    PubMed Central

    Wu, Xian-lin; Li, Jie-xing; Li, Zhen-dong; Liu, Da-sheng; Lu, Su-hong; Liu, Kang-li; Duan, Hong-yan; Luo, Yu-hong

    2015-01-01

    Tet is a type of alkaloid extracted from Stephania tetrandra, and it has recently been demonstrated that Tet can protect against inflammation and free radical injury and inhibit the release of inflammatory mediators. The present study was designed to observe the protective effect of Tet on sodium taurocholate-induced severe acute pancreatitis (SAP). The rat model of SAP was induced by retrograde bile duct injection of sodium taurocholate and then treated with Verapamil and Tet. The results showed that Tet can reduce NF-κB activation in pancreas issue, inhibit the SAP cascade, and improve SAP through inducing pancreas acinar cell apoptosis and stabilizing intracellular calcium in the pancreas, thus mitigating the damage to the pancreas. Our study revealed that Tet may reduce systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndromes (MODS) to protect against damage, and these roles may be mediated through the NF-κB pathway to improve the proinflammatory/anti-inflammatory imbalance. PMID:26557854

  4. Protective Effect of Tetrandrine on Sodium Taurocholate-Induced Severe Acute Pancreatitis.

    PubMed

    Wu, Xian-Lin; Li, Jie-Xing; Li, Zhen-Dong; Liu, Da-Sheng; Lu, Su-Hong; Liu, Kang-Li; Duan, Hong-Yan; Luo, Yu-Hong

    2015-01-01

    Tet is a type of alkaloid extracted from Stephania tetrandra, and it has recently been demonstrated that Tet can protect against inflammation and free radical injury and inhibit the release of inflammatory mediators. The present study was designed to observe the protective effect of Tet on sodium taurocholate-induced severe acute pancreatitis (SAP). The rat model of SAP was induced by retrograde bile duct injection of sodium taurocholate and then treated with Verapamil and Tet. The results showed that Tet can reduce NF-κB activation in pancreas issue, inhibit the SAP cascade, and improve SAP through inducing pancreas acinar cell apoptosis and stabilizing intracellular calcium in the pancreas, thus mitigating the damage to the pancreas. Our study revealed that Tet may reduce systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndromes (MODS) to protect against damage, and these roles may be mediated through the NF-κB pathway to improve the proinflammatory/anti-inflammatory imbalance. PMID:26557854

  5. Severe acute interstitial nephritis after combination immune-checkpoint inhibitor therapy for metastatic melanoma

    PubMed Central

    Murakami, Naoka; Borges, Thiago J.; Yamashita, Michifumi; Riella, Leonardo V.

    2016-01-01

    Immune-checkpoint inhibitors are emerging as revolutionary drugs for certain malignancies. However, blocking the co-inhibitory signals may lead to immune-related adverse events, mainly in the spectrum of autoimmune diseases including colitis, endocrinopathies and nephritis. Here, we report a case of a 75-year-old man with metastatic malignant melanoma treated with a combination of nivolumab (anti-PD1-antibody) and ipilimumab (anti-CTLA-4 antibody) who developed systemic rash along with severe acute tubulointerstitial nephritis after two doses of combination therapy. Kidney biopsy and peripheral blood immune profile revealed highly proliferative and cytotoxic T cell features. Herein, we discuss the pathophysiology and management of immune checkpoint blockade-related adverse events. PMID:27274826

  6. Study progress on mechanism of severe acute pancreatitis complicated with hepatic injury*

    PubMed Central

    Zhang, Xi-ping; Wang, Lei; Zhang, Jie

    2007-01-01

    Study on the action mechanism of inflammatory mediators generated by the severe acute pancreatitis (SAP) in multiple organ injury is a hotspot in the surgical field. In clinical practice, the main complicated organ dysfunctions are shock, respiratory failure, renal failure, encephalopathy, with the rate of hepatic diseases being closely next to them. The hepatic injury caused by SAP cannot only aggravate the state of pancreatitis, but also develop into hepatic failure and cause patient death. Its complicated pathogenic mechanism is an obstacle in clinical treatment. Among many pathogenic factors, the changes of vasoactive substances, participation of inflammatory mediators as well as OFR (oxygen free radical), endotoxin, etc. may play important roles in its progression. PMID:17444596

  7. Admissions to acute adolescent psychiatric units: a prospective study of clinical severity and outcome

    PubMed Central

    2011-01-01

    Background Several countries have established or are planning acute psychiatric in-patient services that accept around-the-clock emergency admission of adolescents. Our aim was to investigate the characteristics and clinical outcomes of a cohort of patients at four Norwegian units. Methods We used a prospective pre-post observational design. Four units implemented a clinician-rated outcome measure, the Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA), which measures mental health problems and their severity. We collected also data about the diagnoses, suicidal problems, family situations, and the involvement of the Child Protection Service. Predictions of outcome (change in HoNOSCA total score) were analysed with a regression model. Results The sample comprised 192 adolescents admitted during one year (response rate 87%). Mean age was 15.7 years (range 10-18) and 70% were girls. Fifty-eight per cent had suicidal problems at intake and the mean intake HoNOSCA total score was 18.5 (SD 6.4). The largest groups of main diagnostic conditions were affective (28%) and externalizing (26%) disorders. Diagnoses and other patient characteristics at intake did not differ between units. Clinical psychiatric disorders and developmental disorders were associated with severity (on HoNOSCA) at intake but not with outcome. Of adolescents ≥ 16 years, 33% were compulsorily admitted. Median length of stay was 8.5 days and 75% of patients stayed less than a month. Compulsory admissions and length of stay varied between units. Mean change (improvement) in the HoNOSCA total score was 5.1 (SD 6.2), with considerable variation between units. Mean discharge score was close to the often-reported outpatient level, and self-injury and emotional symptoms were the most reduced symptoms during the stay. In a regression model, unit, high HoNOSCA total score at intake, or involvement of the Child Protection Service predicted improvement during admission. Conclusions Acute

  8. Intermittent hypoxia and neurorehabilitation.

    PubMed

    Gonzalez-Rothi, Elisa J; Lee, Kun-Ze; Dale, Erica A; Reier, Paul J; Mitchell, Gordon S; Fuller, David D

    2015-12-15

    In recent years, it has become clear that brief, repeated presentations of hypoxia [i.e., acute intermittent hypoxia (AIH)] can boost the efficacy of more traditional therapeutic strategies in certain cases of neurologic dysfunction. This hypothesis derives from a series of studies in animal models and human subjects performed over the past 35 yr. In 1980, Millhorn et al. (Millhorn DE, Eldridge FL, Waldrop TG. Respir Physiol 41: 87-103, 1980) showed that electrical stimulation of carotid chemoafferent neurons produced a persistent, serotonin-dependent increase in phrenic motor output that outlasts the stimulus for more than 90 min (i.e., a "respiratory memory"). AIH elicits similar phrenic "long-term facilitation" (LTF) by a mechanism that requires cervical spinal serotonin receptor activation and de novo protein synthesis. From 2003 to present, a series of studies demonstrated that AIH can induce neuroplasticity in the injured spinal cord, causing functional recovery of breathing capacity after cervical spinal injury. Subsequently, it was demonstrated that repeated AIH (rAIH) can induce recovery of limb function, and the functional benefits of rAIH are greatest when paired with task-specific training. Since uncontrolled and/or prolonged intermittent hypoxia can elicit pathophysiology, a challenge of intermittent hypoxia research is to ensure that therapeutic protocols are well below the threshold for pathogenesis. This is possible since many low dose rAIH protocols have induced functional benefits without evidence of pathology. We propose that carefully controlled rAIH is a safe and noninvasive modality that can be paired with other neurorehabilitative strategies including traditional activity-based physical therapy or cell-based therapies such as intraspinal transplantation of neural progenitors. PMID:25997947

  9. [Risk factors for severe acute lower respiratory tract infection in Bogota, 2001].

    PubMed

    Jaimes, María Belén; Cáceres, Diana C; de la Hoz, Fernando; Gutiérrez, Camilo; Herrera, Diana; Pinilla, Jairo; Porras, Alexandra; Rodríguez, Fabio; Velandia, Martha

    2003-09-01

    Severity of acute respiratory infection is higher in developing countries, especially among the socioeconomically underprivileged. Viral pneumonias are more common, especially among children. A prospective hospital-based case control study was undertaken in Bogota between November 2000 and August 2001, aimed to identify factors related to severe low acute respiratory infection (SLARI). Cases were limited to children aged between 2 months and 5 years who filled WHO criteria for SLARI. Controls were children at the same hospital with ARI in a similar age range, but without symptoms of chest drawing. A total of 638 children (277 cases and 361 controls) were included. The most important risk factors included the following: living in borrowed houses (odds ratio (OR) = 2.7; 95% Confidence Interval (CI): 1.06-7.07), sharing the bed (OR = 1.88, CI: 1.0-3.7), living with more than 9 people (OR = 1.82, CI: 1.0-3.51), and living with smokers (OR = 1.4, CI: 1.0-2.05). Of the 114 samples collected (from children at third day after beginning of symptoms), 98 had viruses, sincitial respiratory virus was the most frequently identified virus (41.8%), followed by influenza A virus (3.1%) and influenza B virus (1%). All positive isolates for influenza A and B were sent to the United States Center for Disease Control (CDC) in Atlanta, where they were classified as influenza A/PANAMA/2007/99-like and influenza B/SICHUAN/379/99-like, respectively. PMID:14582331

  10. Carbon monoxide and Ca2+-activated K+ channels in cerebral arteriolar responses to glutamate and hypoxia in newborn pigs

    PubMed Central

    Kanu, Alie; Leffler, Charles W.

    2008-01-01

    Large conductance calcium activated (KCa) channels regulate the physiological functions of many tissues, including cerebrovascular smooth muscle. L-glutamic acid (glutamate) is the principal excitatory neurotransmitter in the central nervous system and oxygen tension is a dominant local regulator of vascular tone. In vivo, glutamate and hypoxia dilate newborn pig cerebral arterioles and both dilations are blocked by inhibition of CO production. CO dilates cerebral arterioles by activating KCa channels. Therefore, the present study was designed to investigate effects of glutamate and hypoxia on cerebral CO production and the role of KCa channels in the cerebral arteriolar dilations to glutamate and hypoxia. In the presence of iberiotoxin or paxilline that block dilation to the KCa channel opener, NS1619, neither CO nor glutamate dilated pial arterioles. Conversely, neither paxilline nor iberiotoxin inhibited dilation to acute severe or moderate prolonged hypoxia. Both glutamate and hypoxia increased CSF CO concentration. Iberiotoxin that blocked dilation to glutamate did not attenuate the increase in CSF CO. The guanylyl cyclase inhibitor, 1H–(1,2,4) oxadiazolo (4,3-a) quinoxalin-1-one (ODQ), that blocked dilation to sodium nitroprusside did not inhibit dilation to hypoxia. These data suggest that dilation of newborn pig pial arterioles to glutamate is mediated by activation of KCa channels consistent with the intermediary signal being CO. Surprisingly, although heme oxygenase (HO) inhibition attenuates dilation to hypoxia, hypoxia increases CSF CO concentration, and KCa channel antagonists block dilation to CO, neither KCa channel blockers nor ODQ altered dilation to hypoxia suggesting the contribution of the HO/CO system to hypoxia-induced dilation is not by stimulating vascular smooth muscle KCa channels or guanylyl cyclase. PMID:17766483

  11. Severe but reversible acute kidney injury resulting from Amanita punctata poisoning

    PubMed Central

    Kang, Eunjung; Cheong, Ka-Young; Lee, Min-Jeong; Kim, Seirhan; Shin, Gyu-Tae; Kim, Heungsoo; Park, In-Whee

    2015-01-01

    Mushroom-related poisoning can cause acute kidney injury. Here we report a case of acute kidney injury after ingestion of Amanita punctata, which is considered an edible mushroom. Gastrointestinal symptoms occurred within 24 hours from the mushroom intake and were followed by an asymptomatic period, acute kidney injury, and elevation of liver and pancreatic enzymes. Kidney function recovered with supportive care. Nephrotoxic mushroom poisoning should be considered as a cause of acute kidney injury. PMID:26779427

  12. Expression, purification and characterization of recombinant severe acute respiratory syndrome coronavirus non-structural protein 1

    PubMed Central

    Brucz, Kimberly; Miknis, Zachary J.; Schultz, L. Wayne; Umland, Timothy C.

    2007-01-01

    The coronavirus (CoV) responsible for severe acute respiratory syndrome (SARS), SARS-CoV, encodes two large polyproteins (pp1a and pp1ab) that are processed by two viral proteases to yield mature non-structural proteins (nsps). Many of these nsps have essential roles in viral replication, but several have no assigned function and possess amino acid sequences that are unique to the CoV family. One such protein is SARS-CoV nsp1, which is processed from the N-terminus of both pp1a and pp1ab. The mature SARS-CoV protein is present in cells several hours post-infection and co-localizes to the viral replication complex, but its function in the viral life cycle remains unknown. Furthermore, nsp1 sequences are highly divergent across the CoV family, and it has been suggested that this is due to nsp1 possessing a function specific to viral interactions with its host cell or acting as a host specific virulence factor. In order to initiate structural and biophysical studies of SARS-CoV nsp1, a recombinant expression system and a purification protocol have been developed, yielding milligram quantities of highly purified SARS-CoV nsp1. The purified protein was characterized using circular dichroism, size exclusion chromatography, and multi-angle light scattering. PMID:17187987

  13. Severe Acute Respiratory Illness (SARI) Surveillance in Louisiana, 2013-2014.

    PubMed

    Hand, Julie P; Serrano, Jose; Johnson, Jenna I; Jespersen, Megan; Ratard, Raoult C

    2015-01-01

    The objectives of this article are to describe the severe acute respiratory illness (SARI) surveillance implemented in Louisiana during the 2013-2014 influenza season, present the epidemiology of reported SARI cases, and identify ways to improve this system by incorporating formal SARI surveillance into the influenza surveillance program. Of the 212 SARI cases, 181 (85%) had at least one underlying medical condition, 54 (25.7%) had two conditions, 43 (20.3%) had three conditions, and 25 (11.8%) reported four or more. The most common four underlying conditions were: obesity (43.4%), chronic cardiac conditions (39.6%), diabetes (29.7%), and chronic pulmonary conditions (26.9%). While obesity was the most reported underlying condition, it was three times more likely to be reported in less than 65 years old rather than those >65. Continuation of SARI data collection in future seasons will allow comparisons regarding severity, populations affected, and identify risk factors most commonly associated with severe illness. Reporting of SARI cases also increased influenza-associated adult mortality reporting to the Office of Public Health's Office of Infectious Diseases Epidemiology (ID Epi). Though all influenza-associated mortality is reportable in Louisiana, adult mortality was reported rarely prior to the 2013-2014 season. PMID:27159455

  14. Structural and Functional Analyses of the Severe Acute Respiratory Syndrome Coronavirus Endoribonuclease Nsp15

    SciTech Connect

    Bhardwaj, Kanchan; Palaninathan, Satheesh; Alcantara, Joanna Maria Ortiz; Yi, Lillian Li; Guarino, Linda; Sacchettini, James C.; Kao, C. Cheng

    2008-03-31

    The severe acute respiratory syndrome (SARS) coronavirus encodes several RNA-processing enzymes that are unusual for RNA viruses, including Nsp15 (nonstructural protein 15), a hexameric endoribonuclease that preferentially cleaves 3' of uridines. We solved the structure of a catalytically inactive mutant version of Nsp15, which was crystallized as a hexamer. The structure contains unreported flexibility in the active site of each subunit. Substitutions in the active site residues serine 293 and proline 343 allowed Nsp15 to cleave at cytidylate, whereas mutation of leucine 345 rendered Nsp15 able to cleave at purines as well as pyrimidines. Mutations that targeted the residues involved in subunit interactions generally resulted in the formation of catalytically inactive monomers. The RNA-binding residues were mapped by a method linking reversible cross-linking, RNA affinity purification, and peptide fingerprinting. Alanine substitution of several residues in the RNA-contacting portion of Nsp15 did not affect hexamer formation but decreased the affinity of RNA binding and reduced endonuclease activity. This suggests a model for Nsp15 hexamer interaction with RNA.

  15. Bone scintigraphy in acute renal failure with severe loin pain and patchy renal vasoconstriction.

    PubMed

    Han, J S; Kim, Y G; Kim, S; Lee, M C; Lee, J S; Kim, S H

    1991-01-01

    To evaluate the patterns of renal images and the diagnostic value as a screening test of the whole-body bone and renal scintigraphy with technetium-99m-methylene diphosphonate (99mTc-MDP) or -pyrophosphate (99mTc-PYP), we performed bone scintigraphy in 6 patients with acute renal failure (ARF) with severe loin pain and patchy renal vasoconstriction on postcontrast renal computed tomography (CT). All 6 patients were young and previously healthy but experienced severe loin pain after track events. Five took analgesics. Postcontrast renal CT showed patchy low-density areas or diffuse enhancement immediately after radiocontrast injection and then patchy wedge-shaped enhancement 24 or 48 h later, which subsequently disappeared 72 h later. On the whole-body bone scintigrams with 99mTc-MDP or 99mTc-PYP before obtaining renal CT, there was no increased uptake of isotope in the soft tissue, and multiple patchy increased accumulations of the isotope in the kidney were observed in 5 patients. In 2 patients, renal scintigraphies with technetium-99m-dimercaptosuccinate showed photon-deficient areas in the same areas of patchy isotope accumulation in the whole-body bone scintigraphies. Whole-body image and renal scintigraphy with bone-seeking agents may be useful as a screening test and in the search for the theoretical evidence of ARF with severe loin pain and patchy renal vasoconstriction. PMID:1835520

  16. Oxygen sensing by the carotid body: mechanisms and role in adaptation to hypoxia.

    PubMed

    López-Barneo, José; González-Rodríguez, Patricia; Gao, Lin; Fernández-Agüera, M Carmen; Pardal, Ricardo; Ortega-Sáenz, Patricia

    2016-04-15

    Oxygen (O2) is fundamental for cell and whole-body homeostasis. Our understanding of the adaptive processes that take place in response to a lack of O2(hypoxia) has progressed significantly in recent years. The carotid body (CB) is the main arterial chemoreceptor that mediates the acute cardiorespiratory reflexes (hyperventilation and sympathetic activation) triggered by hypoxia. The CB is composed of clusters of cells (glomeruli) in close contact with blood vessels and nerve fibers. Glomus cells, the O2-sensitive elements in the CB, are neuron-like cells that contain O2-sensitive K(+)channels, which are inhibited by hypoxia. This leads to cell depolarization, Ca(2+)entry, and the release of transmitters to activate sensory fibers terminating at the respiratory center. The mechanism whereby O2modulates K(+)channels has remained elusive, although several appealing hypotheses have been postulated. Recent data suggest that mitochondria complex I signaling to membrane K(+)channels plays a fundamental role in acute O2sensing. CB activation during exposure to low Po2is also necessary for acclimatization to chronic hypoxia. CB growth during sustained hypoxia depends on the activation of a resident population of stem cells, which are also activated by transmitters released from the O2-sensitive glomus cells. These advances should foster further studies on the role of CB dysfunction in the pathogenesis of highly prevalent human diseases. PMID:26764048

  17. Improving management of severe sepsis and uptake of sepsis resuscitation bundle in an acute setting

    PubMed Central

    Kafle, Sumitra; Nath, Navdeep

    2014-01-01

    Severe sepsis still remains a major cause of morbidity and mortality, claiming between 36,000 to 64,000 lives annually in the UK, with a mortality rate of 35%.[1,2] The project aims to measure the management of severely septic patients in acute medical unit (AMU) in a district general hospital against best practice guidelines, before and after a set of interventions aiming to optimise patient management and outcomes. All new admissions who met the criteria for sepsis in AMU over a two week period were evaluated. Those who met the criteria for severe sepsis were further analysed. The criteria evaluated were time to first administration of oxygen, intravenous fluids, antibiotics, the taking of blood cultures, other relevant bloods tests (including lactate) and urine output monitoring. A re-audit was completed after the introduction of a set of interventions which included a “sepsis box.” A total of 32 patients (19 Males, 13 Females) were identified in the pre-intervention group. Twenty-two of these patients met the criteria for severe sepsis. Only 15 out of 32 (47%) had their lactate measured. Ten out of 22 (45%) received fluids within an hour. Twelve out of 22 (55%) had their blood culture sample taken after administration of antibiotics and only 12 out of 22 (55%) had antibiotics administrated within an hour of medical assessment. Post-intervention the results however improved dramatically. A total of 30 patients were identified in the post-intervention group (12 Males, 18 Females). Antibiotics administration within an hour went up by 22%. Lactate was performed in 26/30 (87%) patients presented with sepsis compared to 47% in the pre-intervention group. Similarly, identification of severe sepsis, and administration of intravenous fluids also showed improvement ultimately improving patient safety. Following the initial success, the trial was repeated over three months period, which showed sustainable improvement. PMID:26734299

  18. Early increase in intestinal permeability in patients with severe acute pancreatitis: correlation with endotoxemia, organ failure, and mortality.

    PubMed

    Ammori, B J; Leeder, P C; King, R F; Barclay, G R; Martin, I G; Larvin, M; McMahon, M J

    1999-01-01

    Sepsis accounts for 80% of deaths from acute pancreatitis. This study aimed to investigate early changes in intestinal permeability in patients with acute pancreatitis, and to correlate these changes with subsequent disease severity and endotoxemia. The renal excretion of enterally administered polyethylene glycol (PEG) 3350 and PEG 400 was measured within 72 hours of onset of acute pancreatitis to determine intestinal permeability. Severity was assessed on the basis of APACHE II scores and C-reactive protein measurements. Serum endotoxin and antiendotoxin antibodies were measured on admission. Eight-five patients with acute pancreatitis (mild in 56, severe in 29) and 25 healthy control subjects were studied. Urinary excretion of PEG 3350 (median) was significantly greater in patients who had severe attacks (0.61%) compared to those with mild disease (0.09%) and health control subjects (0.12%) (P <0. 0001), as was the permeability index (PEG 3350/400 excretion) (P <0. 00001). The permeability index was significantly greater in patients who subsequently developed multiple organ system failure and/or died compared with other severe cases (0.16 vs. 0.04) (P = 0.0005). The excretion of PEG 3350 correlated strongly with endotoxemia (r = 0.8; P = 0.002). Early increased intestinal permeability may play an important role in the pathophysiology of severe acute pancreatitis. Therapies that aim to restore intestinal barrier function may improve outcome. PMID:10481118

  19. Therapeutic potential of intermittent hypoxia: a matter of dose

    PubMed Central

    Navarrete-Opazo, Angela

    2014-01-01

    Intermittent hypoxia (IH) has been the subject of considerable research in recent years, and triggers a bewildering array of both detrimental and beneficial effects in multiple physiological systems. Here, we review the extensive literature concerning IH and its impact on the respiratory, cardiovascular, immune, metabolic, bone, and nervous systems. One major goal is to define relevant IH characteristics leading to safe, protective, and/or therapeutic effects vs. pathogenesis. To understand the impact of IH, it is essential to define critical characteristics of the IH protocol under investigation, including potentially the severity of hypoxia within episodes, the duration of hypoxic episodes, the number of hypoxic episodes per day, the pattern of presentation across time (e.g., within vs. consecutive vs. alternating days), and the cumulative time of exposure. Not surprisingly, severe/chronic IH protocols tend to be pathogenic, whereas any beneficial effects are more likely to arise from modest/acute IH exposures. Features of the IH protocol most highly associated with beneficial vs. pathogenic outcomes include the level of hypoxemia within episodes and the number of episodes per day. Modest hypoxia (9–16% inspired O2) and low cycle numbers (3–15 episodes per day) most often lead to beneficial effects without pathology, whereas severe hypoxia (2–8% inspired O2) and more episodes per day (48–2,400 episodes/day) elicit progressively greater pathology. Accumulating evidence suggests that “low dose” IH (modest hypoxia, few episodes) may be a simple, safe, and effective treatment with considerable therapeutic potential for multiple clinical disorders. PMID:25231353

  20. Protein source and quality in therapeutic foods affect the immune response and outcome in severe acute malnutrition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Protein is a vital component of therapeutic foods designed to treat severe acute malnutrition (SAM) in children; however there are still unknowns about the quality and quantity of the proteins to use in these foods. This review examines two recent studies investigating several different qualities an...

  1. Immune Responses in Acute and Convalescent Patients with Mild, Moderate and Severe Disease during the 2009 Influenza Pandemic in Norway

    PubMed Central

    Mohn, Kristin G.-I.; Cox, Rebecca Jane; Tunheim, Gro; Berdal, Jan Erik; Hauge, Anna Germundsson; Jul-Larsen, Åsne; Peters, Bjoern; Oftung, Fredrik

    2015-01-01

    Increased understanding of immune responses influencing clinical severity during pandemic influenza infection is important for improved treatment and vaccine development. In this study we recruited 46 adult patients during the 2009 influenza pandemic and characterized humoral and cellular immune responses. Those included were either acute hospitalized or convalescent patients with different disease severities (mild, moderate or severe). In general, protective antibody responses increased with enhanced disease severity. In the acute patients, we found higher levels of TNF-α single-producing CD4+T-cells in the severely ill as compared to patients with moderate disease. Stimulation of peripheral blood mononuclear cells (PBMC) from a subset of acute patients with peptide T-cell epitopes showed significantly lower frequencies of influenza specific CD8+ compared with CD4+ IFN-γ T-cells in acute patients. Both T-cell subsets were predominantly directed against the envelope antigens (HA and NA). However, in the convalescent patients we found high levels of both CD4+ and CD8+ T-cells directed against conserved core antigens (NP, PA, PB, and M). The results indicate that the antigen targets recognized by the T-cell subsets may vary according to the phase of infection. The apparent low levels of cross-reactive CD8+ T-cells recognizing internal antigens in acute hospitalized patients suggest an important role for this T-cell subset in protective immunity against influenza. PMID:26606759

  2. Severity of Acute Respiratory Distress Syndrome in haematology patients: long-term impact and early predictive factors.

    PubMed

    Lagier, D; Platon, L; Chow-Chine, L; Sannini, A; Bisbal, M; Brun, J-P; Blache, J-L; Faucher, M; Mokart, D

    2016-09-01

    Severe forms of acute respiratory distress syndrome in patients with haematological diseases expose clinicians to specific medical and ethical considerations. We prospectively followed 143 patients with haematological malignancies, and whose lungs were mechanically ventilated for more than 24 h, over a 5-y period. We sought to identify prognostic factors of long-term outcome, and in particular to evaluate the impact of the severity of acute respiratory distress syndrome in these patients. A secondary objective was to identify the early (first 48 h from ICU admission) predictive factors for acute respiratory distress syndrome severity. An evolutive haematological disease (HR 1.71; 95% CI 1.13-2.58), moderate to severe acute respiratory distress syndrome (HR 1.81; 95% CI 1.13-2.69) and need for renal replacement therapy (HR 2.24; 95% CI 1.52-3.31) were associated with long-term mortality. Resolution of neutropaenia during ICU stay (HR 0.63; 95% CI 0.42-0.94) and early microbiological documentation (HR 0.62; 95% CI 0.42-0.91) were associated with survival. The extent of pulmonary infiltration observed on the first chest X-ray and the diagnosis of invasive fungal infection were the most relevant early predictive factors of the severity of acute respiratory distress syndrome. PMID:27418297

  3. Severe acute respiratory syndrome coronavirus envelope protein ion channel activity promotes virus fitness and pathogenesis.

    PubMed

    Nieto-Torres, Jose L; DeDiego, Marta L; Verdiá-Báguena, Carmina; Jimenez-Guardeño, Jose M; Regla-Nava, Jose A; Fernandez-Delgado, Raul; Castaño-Rodriguez, Carlos; Alcaraz, Antonio; Torres, Jaume; Aguilella, Vicente M; Enjuanes, Luis

    2014-05-01

    Deletion of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) envelope (E) gene attenuates the virus. E gene encodes a small multifunctional protein that possesses ion channel (IC) activity, an important function in virus-host interaction. To test the contribution of E protein IC activity in virus pathogenesis, two recombinant mouse-adapted SARS-CoVs, each containing one single amino acid mutation that suppressed ion conductivity, were engineered. After serial infections, mutant viruses, in general, incorporated compensatory mutations within E gene that rendered active ion channels. Furthermore, IC activity conferred better fitness in competition assays, suggesting that ion conductivity represents an advantage for the virus. Interestingly, mice infected with viruses displaying E protein IC activity, either with the wild-type E protein sequence or with the revertants that restored ion transport, rapidly lost weight and died. In contrast, mice infected with mutants lacking IC activity, which did not incorporate mutations within E gene during the experiment, recovered from disease and most survived. Knocking down E protein IC activity did not significantly affect virus growth in infected mice but decreased edema accumulation, the major determinant of acute respiratory distress syndrome (ARDS) leading to death. Reduced edema correlated with lung epithelia integrity and proper localization of Na+/K+ ATPase, which participates in edema resolution. Levels of inflammasome-activated IL-1β were reduced in the lung airways of the animals infected with viruses lacking E protein IC activity, indicating that E protein IC function is required for inflammasome activation. Reduction of IL-1β was accompanied by diminished amounts of TNF and IL-6 in the absence of E protein ion conductivity. All these key cytokines promote the progression of lung damage and ARDS pathology. In conclusion, E protein IC activity represents a new determinant for SARS-CoV virulence. PMID:24788150

  4. Differences in spontaneous breathing pattern and mechanics in patients with severe COPD recovering from acute exacerbation.

    PubMed

    Vitacca, M; Porta, R; Bianchi, L; Clini, E; Ambrosino, N

    1999-02-01

    The aims of this study were to assess spontaneous breathing patterns in patients with chronic obstructive pulmonary disease (COPD) recovering from acute exacerbation and to assess the relationship between different breathing patterns and clinical and functional parameters of respiratory impairment. Thirty-four COPD patients underwent assessment of lung function tests, arterial blood gases, haemodynamics, breathing pattern (respiratory frequency (fR), tidal volume (VT), inspiratory and expiratory time (tI and tE), duty cycle (tI/ttot), VT/tI) and mechanics (oesophageal pressure (Poes), work of breathing (WOB), pressure-time product and index, and dynamic intrinsic positive end-expiratory pressure (PEEPi,dyn)). According to the presence (group 1) or absence (group 2) of Poes swings during the expiratory phase (premature inspiration), 20 (59%) patients were included in group 1 and 14 (41%) in group 2. Premature inspirations were observed 4.5+/-6.4 times x min(-1) (range 1-31), i.e. 20+/-21% (3.7-100%) of total fR calculated from VT tracings. In group 1 the coefficient of variation in VT, tE, tI/ttot, PEEPi,dyn, Poes and WOB of the eight consecutive breaths immediately preceding the premature inspiration was greater than that of eight consecutive breaths in group 2. There were no significant differences in the assessed parameters between the two groups in the overall population, whereas patients with chronic hypoxaemia in group 1 showed a more severe impairment in clinical conditions, mechanics and lung function than hypoxaemic patients in group 2. In spontaneously breathing patients with chronic obstructive pulmonary disease recovering from an acute exacerbation, detectable activity of inspiratory muscles during expiration was found in more than half of the cases. This phenomenon was not associated with any significant differences in anthropometric, demographic, physiological or clinical characteristics. PMID:10065683

  5. Severe Acute Respiratory Syndrome Coronavirus Envelope Protein Ion Channel Activity Promotes Virus Fitness and Pathogenesis

    PubMed Central

    Nieto-Torres, Jose L.; DeDiego, Marta L.; Verdiá-Báguena, Carmina; Jimenez-Guardeño, Jose M.; Regla-Nava, Jose A.; Fernandez-Delgado, Raul; Castaño-Rodriguez, Carlos; Alcaraz, Antonio; Torres, Jaume; Aguilella, Vicente M.; Enjuanes, Luis

    2014-01-01

    Deletion of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) envelope (E) gene attenuates the virus. E gene encodes a small multifunctional protein that possesses ion channel (IC) activity, an important function in virus-host interaction. To test the contribution of E protein IC activity in virus pathogenesis, two recombinant mouse-adapted SARS-CoVs, each containing one single amino acid mutation that suppressed ion conductivity, were engineered. After serial infections, mutant viruses, in general, incorporated compensatory mutations within E gene that rendered active ion channels. Furthermore, IC activity conferred better fitness in competition assays, suggesting that ion conductivity represents an advantage for the virus. Interestingly, mice infected with viruses displaying E protein IC activity, either with the wild-type E protein sequence or with the revertants that restored ion transport, rapidly lost weight and died. In contrast, mice infected with mutants lacking IC activity, which did not incorporate mutations within E gene during the experiment, recovered from disease and most survived. Knocking down E protein IC activity did not significantly affect virus growth in infected mice but decreased edema accumulation, the major determinant of acute respiratory distress syndrome (ARDS) leading to death. Reduced edema correlated with lung epithelia integrity and proper localization of Na+/K+ ATPase, which participates in edema resolution. Levels of inflammasome-activated IL-1β were reduced in the lung airways of the animals infected with viruses lacking E protein IC activity, indicating that E protein IC function is required for inflammasome activation. Reduction of IL-1β was accompanied by diminished amounts of TNF and IL-6 in the absence of E protein ion conductivity. All these key cytokines promote the progression of lung damage and ARDS pathology. In conclusion, E protein IC activity represents a new determinant for SARS-CoV virulence. PMID:24788150

  6. Acute toxicity of zinc to several aquatic species native to the Rocky Mountains.

    PubMed

    Brinkman, Stephen F; Johnston, Walter D

    2012-02-01

    National water-quality criteria for the protection of aquatic life are based on toxicity tests, often using organisms that are easy to culture in the laboratory. Species native to the Rocky Mountains are poorly represented in data sets used to derive national water-quality criteria. To provide additional data on the toxicity of zinc, several laboratory acute-toxicity tests were conducted with a diverse assortment of fish, benthic invertebrates, and an amphibian native to the Rocky Mountains. Tests with fish were conducted using three subspecies of cutthroat trout (Colorado River cutthroat trout Oncorhynchus clarkii pleuriticus, greenback cutthroat trout O. clarkii stomias, and Rio Grande cutthroat trout O. clarkii virginalis), mountain whitefish (Prosopium williamsoni), mottled sculpin (Cottus bairdi), longnose dace (Rhinichthys cataractae), and flathead chub (Platygobio gracilis). Aquatic invertebrate tests were conducted with mayflies (Baetis tricaudatus, Drunella doddsi, Cinygmula sp. and Ephemerella sp.), a stonefly (Chloroperlidae), and a caddis fly (Lepidostoma sp.). The amphibian test was conducted with tadpoles of the boreal toad (Bufo boreas). Median lethal concentrations (LC(50)s) ranged more than three orders of magnitude from 166 μg/L for Rio Grande cutthroat trout to >67,000 μg/L for several benthic invertebrates. Of the organisms tested, vertebrates were the most sensitive, and benthic invertebrates were the most tolerant. PMID:21811884

  7. Increased Gut Redox and Depletion of Anaerobic and Methanogenic Prokaryotes in Severe Acute Malnutrition

    PubMed Central

    Million, Matthieu; Tidjani Alou, Maryam; Khelaifia, Saber; Bachar, Dipankar; Lagier, Jean-Christophe; Dione, Niokhor; Brah, Souleymane; Hugon, Perrine; Lombard, Vincent; Armougom, Fabrice; Fromonot, Julien; Robert, Catherine; Michelle, Caroline; Diallo, Aldiouma; Fabre, Alexandre; Guieu, Régis; Sokhna, Cheikh; Henrissat, Bernard; Parola, Philippe; Raoult, Didier

    2016-01-01

    Severe acute malnutrition (SAM) is associated with inadequate diet, low levels of plasma antioxidants and gut microbiota alterations. The link between gut redox and microbial alterations, however, remains unexplored. By sequencing the gut microbiomes of 79 children of varying nutritional status from three centers in Senegal and Niger, we found a dramatic depletion of obligate anaerobes in malnutrition. This was confirmed in an individual patient data meta-analysis including 107 cases and 77 controls from 5 different African and Asian countries. Specifically, several species of the Bacteroidaceae, Eubacteriaceae, Lachnospiraceae and Ruminococceae families were consistently depleted while Enterococcus faecalis, Escherichia coli and Staphylococcus aureus were consistently enriched. Further analyses on our samples revealed increased fecal redox potential, decreased total bacterial number and dramatic Methanobrevibacter smithii depletion. Indeed, M. smithii was detected in more than half of the controls but in none of the cases. No causality was demonstrated but, based on our results, we propose a unifying theory linking microbiota specificity, lacking anaerobes and archaea, to low antioxidant nutrients, and lower food conversion. PMID:27183876

  8. Severe acute respiratory syndrome--a new coronavirus from the Chinese dragon's lair.

    PubMed

    Knudsen, T B; Kledal, T N; Andersen, O; Eugen-Olsen, J; Kristiansen, T B

    2003-09-01

    The recent identification of a novel clinical entity, the severe acute respiratory syndrome (SARS), the rapid subsequent spread and case fatality rates of 14-15% have prompted a massive international collaborative investigation facilitated by a network of laboratories established by the World Health Organization (WHO). As SARS has the potential of becoming the first pandemic of the new millennium, a global warning by the WHO was issued on 12 March 2003. The disease, which is believed to have its origin in the Chinese Guangdong province, spread from Hong Kong via international airports to its current worldwide distribution. The concerted efforts of a globally united scientific community have led to the independent isolation and identification of a novel coronavirus from SARS patients by several groups. The extraordinarily rapid isolation of a causative agent of this newly emerged infectious disease constitutes an unprecedented scientific achievement. The main scope of the article is to provide the clinician with an overview of the natural history, epidemiology and clinical characteristics of SARS. On the basis of the recently published viral genome and structural features common to the members of the coronavirus family, a model for host cell-virus interaction and possible targets for antiviral drugs are presented. The epidemiological consequences of introducing a novel pathogen in a previously unexposed population and the origin and evolution of a new and more pathogenic strain of coronavirus are discussed. PMID:12950672

  9. Increased Gut Redox and Depletion of Anaerobic and Methanogenic Prokaryotes in Severe Acute Malnutrition.

    PubMed

    Million, Matthieu; Tidjani Alou, Maryam; Khelaifia, Saber; Bachar, Dipankar; Lagier, Jean-Christophe; Dione, Niokhor; Brah, Souleymane; Hugon, Perrine; Lombard, Vincent; Armougom, Fabrice; Fromonot, Julien; Robert, Catherine; Michelle, Caroline; Diallo, Aldiouma; Fabre, Alexandre; Guieu, Régis; Sokhna, Cheikh; Henrissat, Bernard; Parola, Philippe; Raoult, Didier

    2016-01-01

    Severe acute malnutrition (SAM) is associated with inadequate diet, low levels of plasma antioxidants and gut microbiota alterations. The link between gut redox and microbial alterations, however, remains unexplored. By sequencing the gut microbiomes of 79 children of varying nutritional status from three centers in Senegal and Niger, we found a dramatic depletion of obligate anaerobes in malnutrition. This was confirmed in an individual patient data meta-analysis including 107 cases and 77 controls from 5 different African and Asian countries. Specifically, several species of the Bacteroidaceae, Eubacteriaceae, Lachnospiraceae and Ruminococceae families were consistently depleted while Enterococcus faecalis, Escherichia coli and Staphylococcus aureus were consistently enriched. Further analyses on our samples revealed increased fecal redox potential, decreased total bacterial number and dramatic Methanobrevibacter smithii depletion. Indeed, M. smithii was detected in more than half of the controls but in none of the cases. No causality was demonstrated but, based on our results, we propose a unifying theory linking microbiota specificity, lacking anaerobes and archaea, to low antioxidant nutrients, and lower food conversion. PMID:27183876

  10. Patterns and severity of vincristine-induced peripheral neuropathy in children with acute lymphoblastic leukemia

    PubMed Central

    Smith, Ellen M. Lavoie; Li, Lang; Chiang, ChienWei; Thomas, Karin; Hutchinson, Raymond J.; Wells, Elizabeth M.; Ho, Richard H.; Skiles, Jodi; Chakraborty, Arindom; Bridges, Celia M.; Renbarger, Jamie

    2015-01-01

    Vincristine, a critical component of combination chemotherapy treatment for pediatric acute lymphoblastic leukemia (ALL), can lead to vincristine-induced peripheral neuropathy (VIPN). Longitudinal VIPN assessments were obtained over 12 months from newly diagnosed children with ALL (N = 128) aged 1–18 years who received vincristine at one of four academic children’s hospitals. VIPN assessments were obtained using the Total Neuropathy Score-Pediatric Vincristine (TNS©-PV), National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE©), Balis© grading scale, and Pediatric Neuropathic Pain Scale©–Five (PNPS©-5). Of children who provided a full TNS©-PV score, 85/109 (78%) developed VIPN (TNS©-PV ≥4). Mean TNS©-PV, grading scale, and pain scores were low. CTCAE©-derived grades 3 and 4 sensory and motor VIPN occurred in 1.6%/0%, and 1.9%/0% of subjects, respectively. VIPN did not resolve in months 8–12 despite decreasing dose density. VIPN was worse in older children. Partition cluster analysis revealed 2–3 patient clusters; one cluster (n = 14) experienced severe VIPN. In this population, VIPN occurs more commonly than previous research suggests, persists throughout the first year of treatment, and can be severe. PMID:25977177

  11. Correlation of NLRP3 with severity and prognosis of coronary atherosclerosis in acute coronary syndrome patients.

    PubMed

    Afrasyab, Altaf; Qu, Peng; Zhao, Yang; Peng, Kuang; Wang, Hongyan; Lou, Dayuan; Niu, Nan; Yuan, Dajun

    2016-08-01

    We decided to assess the prognostic value of NLRP3 inflammasome level in acute coronary syndrome (ACS) patients and whether it was related to coronary atherosclerotic severity. Study population included one-hundred and twenty-three (123) subjects. Peripheral blood monocyte NLRP3 protein level was correlated with clinical presentation, angiographic characteristics and its scoring systems as well as GRACE and TIMI risk scores. Follow-up for major adverse cardiac events (MACE) was carried out at 180 days. Peripheral blood monocyte NLRP3 was found to be elevated in ACS patients (P < 0.05) and showed positive correlation with GRACE score (r = 0.619), TIMI score (r = 0.580), SYNTAX score (r = 0.550), Clinical SYNTAX score (r = 0.564) and Gensini score (r = 0.516). NLRP3 was also increased with increasing number of vessels, the number of lesions present and the presence bifurcation lesions (P < 0.05). Multivariate Cox regression analysis showed NLRP3 to be an independent predictor of MACE (P = 0.043). Kaplan-Meier analysis and receiver operating characteristic curves for NLRP3 showed good predictive value for MACE. There is a positive correlation of NLRP3 level with severity of coronary atherosclerosis. NLRP3 level is a promising prognostic utility and is efficient in event prediction for MACE. PMID:26290166

  12. Serum Levels of Substance P and Mortality in Patients with a Severe Acute Ischemic Stroke.

    PubMed

    Lorente, Leonardo; Martín, María M; Almeida, Teresa; Pérez-Cejas, Antonia; Ramos, Luis; Argueso, Mónica; Riaño-Ruiz, Marta; Solé-Violán, Jordi; Hernández, Mariano

    2016-01-01

    Substance P (SP), a member of tachykinin family, is involved in the inflammation of the central nervous system and in the appearance of cerebral edema. Higher serum levels of SP have been found in 18 patients with cerebral ischemia compared with healthy controls. The aim of our multi-center study was to analyze the possible association between serum levels of SP and mortality in ischemic stroke patients. We included patients with malignant middle cerebral artery infarction (MMCAI) and a Glasgow Coma Scale (GCS) lower than 9. Non-surviving patients at 30 days (n = 31) had higher serum concentrations of SP levels at diagnosis of severe MMCAI than survivors (n = 30) (p < 0.001). We found in multiple regression an association between serum concentrations of SP higher than 362 pg/mL and mortality at 30 days (Odds Ratio = 5.33; 95% confidence interval = 1.541-18.470; p = 0.008) after controlling for age and GCS. Thus, the major novel finding of our study was the association between serum levels of SP and mortality in patients suffering from severe acute ischemic stroke. PMID:27338372

  13. A case of severe acute exacerbation of Yokkaichi asthma treated with a vibrating mesh nebulizer.

    PubMed

    Yano, Takeshi; Yonaha, Tetsu; Hidaka, Koutaro; Nagahama, Masumi; Koshida, Tomohiro; Matsuoka, Hiroshi; Taniguchi, Masahiko; Tsuneyoshi, Isao

    2016-01-01

    Yokkaichi asthma was one of the most common environmental pollution diseases in Japan in the 1960s and 1970s. The problem of air pollution in Yokkaichi was solved in the 1970s. However, mortality and life expectancy were still affected by the late effects of air pollution in patients with Yokkaichi asthma even in the 2000s. In this case report, we described the experience of successful treatment of a patient with severe asthmatic status due to Yokkaichi asthma. A 40s-year-old man, who was officially certified as a patient with Yokkaichi asthma from his infancy, was admitted to hospital due to acute exacerbation of asthma. Mechanical ventilation, intravenous administration of aminophylline and dexamethasone, enteral administration of montelukast, and a transdermal patch of tulobuterol were started. However, because of the lack of improvement in clinical status, inhalation of procaterol using vibrating mesh nebulizer systems was started. Inhalation of procaterol was used three times a day. After using the vibrating mesh nebulizer, respiratory system compliance and hypercapnia rapidly improved. Bilateral expiratory wheezing was diminished. Weaning from mechanical ventilation was initiated, and on the eighth day of mechanical ventilation, the patient was extubated. Although intractable respiratory failure with decreased respiratory system compliance resulting from the late effects of air pollution and a long-time asthmatic inflammatory condition was observed, the use of a vibrating mesh nebulizer for the inhaled administration of procaterol was useful to relieve severe bronchospasm due to Yokkaichi asthma. PMID:27547723

  14. A Case of Severe Acute Necrotizing Pancreatitis after Administration of Sitagliptin

    PubMed Central

    Sue, Mariko; Yoshihara, Aya; Kuboki, Koji; Hiroi, Naoki; Yoshino, Gen

    2013-01-01

    A 55-year-old Japanese man with a 3-year history of type 2 diabetes mellitus was admitted to our hospital for upper abdominal pain. Control of diabetes mellitus was good with voglibose and metformin, with sitagliptin added to this regimen 8 months prior. His pancreatic enzyme levels were elevated, and abdominal computed tomography (CT) showed diffuse pancreatic swelling with fluid accumulation and ascites of CT grade 3. The patient was diagnosed with severe acute pancreatitis. There were no obvious causes for pancreatitis except the recently administered sitagliptin. Since incretin-related drugs entered the market, the number of incretin-related drugs prescriptions rapidly increased and so did the incidence of pancreatitis. There are several reports suggesting the correlation between incretin-related drugs and pancreatitis, such as a report based on data obtained from the United States Food and Drug Administration (FDA) which revealed a significant correlation between the administration of exenatide or sitagliptin and pancreatitis. However, there also is a report that denied the evidence for such in a large cohort study. The relation between incretin based drugs and pancreatitis is still controversial. PMID:23467428

  15. Serum Levels of Substance P and Mortality in Patients with a Severe Acute Ischemic Stroke

    PubMed Central

    Lorente, Leonardo; Martín, María M.; Almeida, Teresa; Pérez-Cejas, Antonia; Ramos, Luis; Argueso, Mónica; Riaño-Ruiz, Marta; Solé-Violán, Jordi; Hernández, Mariano

    2016-01-01

    Substance P (SP), a member of tachykinin family, is involved in the inflammation of the central nervous system and in the appearance of cerebral edema. Higher serum levels of SP have been found in 18 patients with cerebral ischemia compared with healthy controls. The aim of our multi-center study was to analyze the possible association between serum levels of SP and mortality in ischemic stroke patients. We included patients with malignant middle cerebral artery infarction (MMCAI) and a Glasgow Coma Scale (GCS) lower than 9. Non-surviving patients at 30 days (n = 31) had higher serum concentrations of SP levels at diagnosis of severe MMCAI than survivors (n = 30) (p < 0.001). We found in multiple regression an association between serum concentrations of SP higher than 362 pg/mL and mortality at 30 days (Odds Ratio = 5.33; 95% confidence interval = 1.541–18.470; p = 0.008) after controlling for age and GCS. Thus, the major novel finding of our study was the association between serum levels of SP and mortality in patients suffering from severe acute ischemic stroke. PMID:27338372

  16. Does Viral Co-Infection Influence the Severity of Acute Respiratory Infection in Children?

    PubMed Central

    Pardo-Seco, Jacobo; Gómez-Carballa, Alberto; Martinón-Torres, Nazareth; Salas, Antonio; Martinón-Sánchez, José María; Justicia, Antonio; Rivero-Calle, Irene; Sumner, Edward; Fink, Colin

    2016-01-01

    Background Multiple viruses are often detected in children with respiratory infection but the significance of co-infection in pathogenesis, severity and outcome is unclear. Objectives To correlate the presence of viral co-infection with clinical phenotype in children admitted with acute respiratory infections (ARI). Methods We collected detailed clinical information on severity for children admitted with ARI as part of a Spanish prospective multicenter study (GENDRES network) between 2011–2013. A nested polymerase chain reaction (PCR) approach was used to detect respiratory viruses in respiratory secretions. Findings were compared to an independent cohort collected in the UK. Results 204 children were recruited in the main cohort and 97 in the replication cohort. The number of detected viruses did not correlate with any markers of severity. However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory support requirement (OR: 7.484; P-value < 0.001) and longer hospital length of stay (OR: 1.468; P-value < 0.001). In addition, pneumococcal vaccination was found to be a protective factor in terms of degree of respiratory distress (OR: 2.917; P-value = 0.035), PICU admission (OR: 0.301; P-value = 0.011), lower clinical score (-1.499; P-value = 0.021) respiratory support requirement (OR: 0.324; P-value = 0.016) and oxygen necessity (OR: 0.328; P-value = 0.001). All these findings were replicated in the UK cohort. Conclusion The presence of more than one virus in hospitalized children with ARI is very frequent but it does not seem to have a major clinical impact in terms of severity. However bacterial superinfection increases the severity of the disease course. On the contrary, pneumococcal vaccination plays a protective role. PMID:27096199

  17. Early Assessment of Pancreatic Infections and Overall Prognosis in Severe Acute Pancreatitis by Procalcitonin (PCT)

    PubMed Central

    Rau, Bettina M.; Kemppainen, Esko A.; Gumbs, Andrew A.; Büchler, Markus W.; Wegscheider, Karl; Bassi, Claudio; Puolakkainen, Pauli A.; Beger, Hans G.

    2007-01-01

    Background: Pancreatic infections and sepsis are major complications in severe acute pancreatitis (AP) with significant impact on management and outcome. We investigated the value of Procalcitonin (PCT) for identifying patients at risk to develop pancreatic infections in severe AP. Methods: A total of 104 patients with predicted severe AP were enrolled in five European academic surgical centers within 96 hours of symptom onset. PCT was measured prospectively by a semi-automated immunoassay in each center, C-reactive protein (CRP) was routinely assessed. Both parameters were monitored over a maximum of 21 consecutive days and in weekly intervals thereafter. Results: In contrast to CRP, PCT concentrations were significantly elevated in patients with pancreatic infections and associated multiorgan dysfunction syndrome (MODS) who all required surgery (n = 10) and in nonsurvivors (n = 8) early after onset of symptoms. PCT levels revealed only a moderate increase in patients with pancreatic infections in the absence of MODS (n = 7), all of whom were managed nonoperatively without mortality. A PCT value of ≥3.5 ng/mL on 2 consecutive days was superior to CRP ≥430 mg/L for the assessment of infected necrosis with MODS or nonsurvival as determined by ROC analysis with a sensitivity and specificity of 93% and 88% for PCT and 40% and 100% for CRP, respectively (P < 0.01). The single or combined prediction of the two major complications was already possible on the third and fourth day after onset of symptoms with a sensitivity and specificity of 79% and 93% for PCT ≥3.8 ng/mL compared with 36% and 97% for CRP ≥430 mg/L, respectively (P = 0.002). Conclusion: Monitoring of PCT allows early and reliable assessment of clinically relevant pancreatic infections and overall prognosis in AP. This single test parameter significantly contributes to an improved stratification of patients at risk to develop major complications. PMID:17457167

  18. Risk taking in hospitalized patients with acute and severe traumatic brain injury.

    PubMed

    Fecteau, Shirley; Levasseur-Moreau, Jean; García-Molina, Alberto; Kumru, Hatiche; Vergara, Raúl Pelayo; Bernabeu, Monste; Roig, Teresa; Pascual-Leone, Alvaro; Tormos, José Maria

    2013-01-01

    Rehabilitation can improve cognitive deficits observed in patients with traumatic brain injury (TBI). However, despite rehabilitation, the ability of making a choice often remains impaired. Risk taking is a daily activity involving numerous cognitive processes subserved by a complex neural network. In this work we investigated risk taking using the Balloon Analogue Risk Task (BART) in patients with acute TBI and healthy controls. We hypothesized that individuals with TBI will take less risk at the BART as compared to healthy individuals. We also predicted that within the TBI group factors such as the number of days since the injury, severity of the injury, and sites of the lesion will play a role in risk taking as assessed with the BART. Main findings revealed that participants with TBI displayed abnormally cautious risk taking at the BART as compared to healthy subjects. Moreover, healthy individuals showed increased risk taking throughout the task which is in line with previous work. However, individuals with TBI did not show this increased risk taking during the task. We also investigated the influence of three patients' characteristics on their performance at the BART: Number of days post injury, Severity of the head injury, and Status of the frontal lobe. Results indicate that performance at the BART was influenced by the number of days post injury and the status of the frontal lobe, but not by the severity of the head injury. Reported findings are encouraging for risk taking seems to naturally improve with time postinjury. They support the need of conducting longitudinal prospective studies to ultimately identify impaired and intact cognitive skills that should be trained postinjury. PMID:24386232

  19. Ventilation-perfusion mismatching in acute severe asthma: effects of salbutamol and 100% oxygen.

    PubMed Central

    Ballester, E; Reyes, A; Roca, J; Guitart, R; Wagner, P D; Rodriguez-Roisin, R

    1989-01-01

    Ventilation-perfusion (VA/Q) relationships and gas exchange were studied by the multiple inert gas technique in 19 patients admitted to hospital with acute severe asthma (FEV1 41% predicted) before and during the administration of intravenous salbutamol, inhaled salbutamol, or 100% oxygen. Eight patients received a continuous intravenous infusion of salbutamol (4 micrograms/min, total dose 360 micrograms) and were studied before treatment, after 60 and 90 minutes of treatment, and one hour after treatment had been discontinued. Six patients had measurements before and 15 minutes after inhaling 300 micrograms salbutamol from a metered dose inhaler on two occasions (total dose 600 micrograms) and one hour after the last dose. Measurements were also made in five patients before and while they breathed 100% oxygen for 20 minutes. At baseline (fractional inspired oxygen (FiO2) 21%) all patients showed a broad unimodal (n = 10) or bimodal (n = 9) distribution of blood flow with respect to VA/Q. A mean of 10.5% of the blood flow was associated with low VA/Q units without any appreciable shunt. One of the best descriptors of VA/Q inequality, the second moment of the perfusion distribution on a log scale (log SD Q), was moderately high with a mean of 1.18 (SEM 0.08) (normal less than 0.6). Measures of VA/Q inequality correlated poorly with spirometric findings. After salbutamol the increase in airflow rates was similar regardless of the route of administration. Intravenous salbutamol, however, caused a significant increase in heart rate, cardiac output, and oxygen consumption (VO2); in addition, both perfusion to low VA/Q areas and log SD Q increased significantly. Inhaled salbutamol caused only minor changes in heart rate, cardiac output, VO2, and VA/Q inequality. Arterial oxygen tension (PaO2) remained unchanged during salbutamol administration, irrespective of the route of administration. During 100% oxygen breathing there was a significant increase in log SD Q (from 1

  20. Acute neuro-endocrine profile and prediction of outcome after severe brain injury

    PubMed Central

    2013-01-01

    Object The aim of the study was to evaluate the early changes in pituitary hormone levels after severe traumatic brain injury (sTBI) and compare hormone levels to basic neuro-intensive care data, a systematic scoring of the CT-findings and to evaluate whether hormone changes are related to outcome. Methods Prospective study, including consecutive patients, 15–70 years, with sTBI, Glasgow Coma Scale (GCS) score ≤ 8, initial cerebral perfusion pressure > 10 mm Hg, and arrival to our level one trauma university hospital within 24 hours after head trauma (n = 48). Serum samples were collected in the morning (08–10 am) day 1 and day 4 after sTBI for analysis of cortisol, growth hormone (GH), prolactin, insulin-like growth factor 1 (IGF-1), thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), follicular stimulating hormone (FSH), luteinizing hormone (LH), testosterone and sex hormone-binding globulin (SHBG) (men). Serum for cortisol and GH was also obtained in the evening (17–19 pm) at day 1 and day 4. The first CT of the brain was classified according to Marshall. Independent staff evaluated outcome at 3 months using GOS-E. Results Profound changes were found for most pituitary-dependent hormones in the acute phase after sTBI, i.e. low levels of thyroid hormones, strong suppression of the pituitary-gonadal axis and increased levels of prolactin. The main findings of this study were: 1) A large proportion (54% day 1 and 70% day 4) of the patients showed morning s-cortisol levels below the proposed cut-off levels for critical illness related corticosteroid insufficiency (CIRCI), i.e. <276 nmol/L (=10 ug/dL), 2) Low s-cortisol was not associated with higher mortality or worse outcome at 3 months, 3) There was a significant association between early (day 1) and strong suppression of the pituitary-gonadal axis and improved survival and favorable functional outcome 3 months after sTBI, 4) Significantly lower levels of fT3

  1. Coronavirus Pathogenesis and the Emerging Pathogen Severe Acute Respiratory Syndrome Coronavirus

    PubMed Central

    Weiss, Susan R.; Navas-Martin, Sonia

    2005-01-01

    Coronaviruses are a family of enveloped, single-stranded, positive-strand RNA viruses classified within the Nidovirales order. This coronavirus family consists of pathogens of many animal species and of humans, including the recently isolated severe acute respiratory syndrome coronavirus (SARS-CoV). This review is divided into two main parts; the first concerns the animal coronaviruses and their pathogenesis, with an emphasis on the functions of individual viral genes, and the second discusses the newly described human emerging pathogen, SARS-CoV. The coronavirus part covers (i) a description of a group of coronaviruses and the diseases they cause, including the prototype coronavirus, murine hepatitis virus, which is one of the recognized animal models for multiple sclerosis, as well as viruses of veterinary importance that infect the pig, chicken, and cat and a summary of the human viruses; (ii) a short summary of the replication cycle of coronaviruses in cell culture; (iii) the development and application of reverse genetics systems; and (iv) the roles of individual coronavirus proteins in replication and pathogenesis. The SARS-CoV part covers the pathogenesis of SARS, the developing animal models for infection, and the progress in vaccine development and antiviral therapies. The data gathered on the animal coronaviruses continue to be helpful in understanding SARS-CoV. PMID:16339739

  2. Conformational States of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein Ectodomain

    PubMed Central

    Li, Fang; Berardi, Marcelo; Li, Wenhui; Farzan, Michael; Dormitzer, Philip R.; Harrison, Stephen C.

    2006-01-01

    The severe acute respiratory syndrome coronavirus enters cells through the activities of a spike protein (S) which has receptor-binding (S1) and membrane fusion (S2) regions. We have characterized four sequential states of a purified recombinant S ectodomain (S-e) comprising S1 and the ectodomain of S2. They are S-e monomers, uncleaved S-e trimers, cleaved S-e trimers, and dissociated S1 monomers and S2 trimer rosettes. Lowered pH induces an irreversible transition from flexible, L-shaped S-e monomers to clove-shaped trimers. Protease cleavage of the trimer occurs at the S1-S2 boundary; an ensuing S1 dissociation leads to a major rearrangement of the trimeric S2 and to formation of rosettes likely to represent clusters of elongated, postfusion trimers of S2 associated through their fusion peptides. The states and transitions of S suggest conformational changes that mediate viral entry into cells. PMID:16809285

  3. Corticosteroid therapy for severe acute pancreatitis: a meta-analysis of randomized, controlled trials

    PubMed Central

    Dong, Li-Hua; Liu, Zhong-Min; Wang, Shi-Ji; Zhao, Shu-Jie; Zhang, Dong; Chen, Ying; Wang, Yu-Shan

    2015-01-01

    Background: Recent reports about the benefits of corticosteroid therapy in patients with severe acute pancreatitis (SAP) have shown conflicting results. We aimed to explore the effects of corticosteroid therapy in SAP patients on patient outcomes by performing a meta-analysis. Methods: Databases (Medline, EMBASE, Web of Science, PubMed, Cochrane Library, Chinese Biomedicine Database, and China Academic Journal Full-Text Database) were queried for all relevant, randomized, controlled trials investigating corticosteroid therapy in patients with SAP. Results: Six randomized, controlled trials including 430 SAP patients were identified. Corticosteroid therapy for SAP was associated with reductions in the length of hospital stay, the need for surgical intervention, and the mortality rate (weighted mean difference [WMD]: -9.47, 95% confidence interval [CI]: -16.91 to -2.04, P = 0.01; odds ratio [OR]: 0.35, 95% CI: 0.18-0.67, P = 0.002; OR: 0.45, 95% CI: 0.22-0.94, P = 0.03). There were no significant differences in the complication rates or Physiology and Chronic Health Evaluation II (APACHE II) scores in patients with or without corticosteroid therapy. Conclusion: Corticosteroid therapy may improve outcomes in patients with SAP. PMID:26339332

  4. Advances in clinical diagnosis and treatment of severe acute respiratory syndrome

    PubMed Central

    Nie, Qing-He; Luo, Xin-Dong; Hui, Wu-Li

    2003-01-01

    It has been proved that severe acute respiratory syndrome (SARS) is caused by SARS-associated coronavirus, a novel coronavirus. SARS originated in Guangdong Province, the People's Republic of China at the end of 2002. At present, it has spread to more than 33 countries or regions all over the world and affected 8360 people and killed 764 by May 31, 2003. Identification of the SARS causative agent and development of a diagnostic test are important. Detecting disease in its early stage, understanding its pathways of transmission and implementing specific prevention measures for the disease are dependent upon swift progress. Due to the efforts of the WHO-led network of laboratories testing for SARS, tests for the novel coronavirus have been developed with unprecedented speed. The genome sequence reveals that this coronavirus is only moderately related to other known coronaviruses. WHO established the definitions of suspected and confirmed and probable cases. But the laboratory tests and definitions are limited. Until now, the primary measures included isolation, ribavirin and corticosteroid therapy, mechanical ventilation, etc. Other therapies such as convalescent plasma are being explored. It is necessary to find more effective therapy. There still are many problems to be solved in the course of conquering SARS. PMID:12800213

  5. Potential enhancement of osteoclastogenesis by severe acute respiratory syndrome coronavirus 3a/X1 protein.

    PubMed

    Obitsu, Saemi; Ahmed, Nursarat; Nishitsuji, Hironori; Hasegawa, Atsuhiko; Nakahama, Ken-ichi; Morita, Ikuo; Nishigaki, Kazuo; Hayashi, Takaya; Masuda, Takao; Kannagi, Mari

    2009-01-01

    Severe acute respiratory syndrome coronavirus (SARS-CoV) causes a lung disease with high mortality. In addition, osteonecrosis and bone abnormalities with reduced bone density have been observed in patients following recovery from SARS, which were partly but not entirely explained by the short-term use of steroids. Here, we demonstrate that human monocytes, potential precursors of osteoclasts, partly express angiotensin converting enzyme 2 (ACE2), a cellular receptor of SARS-CoV, and that expression of an accessory protein of SARS-CoV, 3a/X1, in murine macrophage cell line RAW264.7 cells, enhanced NF-kappaB activity and differentiation into osteoclast-like cells in the presence of receptor activator of NF-kappaB ligand (RANKL). Furthermore, human epithelial A549 cells expressed ACE2, and expression of 3a/X1 in these cells up-regulated TNF-alpha, which is known to accelerate osteoclastogenesis. 3a/X1 also enhanced RANKL expression in mouse stromal ST2 cells. These findings indicate that SARS-CoV 3a/X1 might promote osteoclastogenesis by direct and indirect mechanisms. PMID:19685004

  6. Severe hypercalcemia as a form of acute lymphoblastic leukemia presentation in children

    PubMed Central

    Martins, Andreia Luís; Moniz, Marta; Nunes, Pedro Sampaio; Abadesso, Clara; Loureiro, Helena Cristina; Duarte, Ximo; Almeida, Helena Isabel

    2015-01-01

    Hypercalcemia is a rare metabolic disorder in children and is potentially fatal. It has a wide differential diagnosis, including cancer. Here, we report the case of a previously healthy 3-year-old who was admitted to the emergency room with fatigue, hyporeactivity, fever and limping gait that had evolved over 5 days and that was progressively worsening. On examination the patient was unconscious (Glasgow coma score: 8). Laboratory tests indicated severe hypercalcemia (total calcium 21.39mg/dL, ionized calcium 2.93mmol/L) and microcytic anemia. Hyperhydration was initiated, and the child was transferred to the pediatric intensive care unit. Continuous venovenous hemodiafiltration with calcium-free solution was instituted, which brought progressive normalization of serum calcium and an improved state of consciousness. Zoledronate was administered, and metabolic and infectious causes and poisoning were excluded. The bone marrow smear revealed a diagnosis of acute lymphoblastic leukemia. Hypercalcemia associated with malignancy in children is rare and occurs as a form of cancer presentation or recurrence. Continuous venovenous hemodiafiltration should be considered in situations where there is imminent risk to life. PMID:26761480

  7. Severe hypercalcemia as a form of acute lymphoblastic leukemia presentation in children.

    PubMed

    Martins, Andreia Luís; Moniz, Marta; Nunes, Pedro Sampaio; Abadesso, Clara; Loureiro, Helena Cristina; Duarte, Ximo; Almeida, Helena Isabel

    2015-01-01

    Hypercalcemia is a rare metabolic disorder in children and is potentially fatal. It has a wide differential diagnosis, including cancer. Here, we report the case of a previously healthy 3-year-old who was admitted to the emergency room with fatigue, hyporeactivity, fever and limping gait that had evolved over 5 days and that was progressively worsening. On examination the patient was unconscious (Glasgow coma score: 8). Laboratory tests indicated severe hypercalcemia (total calcium 21.39mg/dL, ionized calcium 2.93mmol/L) and microcytic anemia. Hyperhydration was initiated, and the child was transferred to the pediatric intensive care unit. Continuous venovenous hemodiafiltration with calcium-free solution was instituted, which brought progressive normalization of serum calcium and an improved state of consciousness. Zoledronate was administered, and metabolic and infectious causes and poisoning were excluded. The bone marrow smear revealed a diagnosis of acute lymphoblastic leukemia. Hypercalcemia associated with malignancy in children is rare and occurs as a form of cancer presentation or recurrence. Continuous venovenous hemodiafiltration should be considered in situations where there is imminent risk to life. PMID:26761480

  8. Transmission of severe acute respiratory syndrome in dynamical small-world networks

    NASA Astrophysics Data System (ADS)

    Masuda, Naoki; Konno, Norio; Aihara, Kazuyuki

    2004-03-01

    The outbreak of severe acute respiratory syndrome (SARS) is still threatening the world because of a possible resurgence. In the current situation that effective medical treatments such as antiviral drugs are not discovered yet, dynamical features of the epidemics should be clarified for establishing strategies for tracing, quarantine, isolation, and regulating social behavior of the public at appropriate costs. Here we propose a network model for SARS epidemics and discuss why superspreaders emerged and why SARS spread especially in hospitals, which were key factors of the recent outbreak. We suggest that superspreaders are biologically contagious patients, and they may amplify the spreads by going to potentially contagious places such as hospitals. To avoid mass transmission in hospitals, it may be a good measure to treat suspected cases without hospitalizing them. Finally, we indicate that SARS probably propagates in small-world networks associated with human contacts and that the biological nature of individuals and social group properties are factors more important than the heterogeneous rates of social contacts among individuals. This is in marked contrast with epidemics of sexually transmitted diseases or computer viruses to which scale-free network models often apply.

  9. Pulmonary administration of a water-soluble curcumin complex reduces severity of acute lung injury.

    PubMed

    Suresh, Madathilparambil V; Wagner, Matthew C; Rosania, Gus R; Stringer, Kathleen A; Min, Kyoung Ah; Risler, Linda; Shen, Danny D; Georges, George E; Reddy, Aravind T; Parkkinen, Jaakko; Reddy, Raju C

    2012-09-01

    Local or systemic inflammation can result in acute lung injury (ALI), and is associated with capillary leakage, reduced lung compliance, and hypoxemia. Curcumin, a plant-derived polyphenolic compound, exhibits potent anti-inflammatory properties, but its poor solubility and limited oral bioavailability reduce its therapeutic potential. A novel curcumin formulation (CDC) was developed by complexing the compound with hydroxypropyl-γ-cyclodextrin (CD). This results in greatly enhanced water solubility and stability that facilitate direct pulmonary delivery. In vitro studies demonstrated that CDC increased curcumin's association with and transport across Calu-3 human airway epithelial cell monolayers, compared with uncomplexed curcumin solubilized using DMSO or ethanol. Importantly, Calu-3 cell monolayer integrity was preserved after CDC exposure, whereas it was disrupted by equivalent uncomplexed curcumin solutions. We then tested whether direct delivery of CDC to the lung would reduce severity of ALI in a murine model. Fluorescence microscopic examination revealed an association of curcumin with cells throughout the lung. The administration of CDC after LPS attenuated multiple markers of inflammation and injury, including pulmonary edema and neutrophils in bronchoalveolar lavage fluid and lung tissue. CDC also reduced oxidant stress in the lungs and activation of the proinflammatory transcription factor NF-κB. These results demonstrate the efficacy of CDC in a murine model of lung inflammation and injury, and support the feasibility of developing a lung-targeted, curcumin-based therapy for the treatment of patients with ALI. PMID:22312018

  10. [Severe acute respiratory syndrome: the first transmissible disease of the 21st century].

    PubMed

    Nicastri, Emanuele; Petrosillo, Nicola; Macrì, Giulia; Ippolito, Giuseppe

    2003-01-01

    The Severe Acute Respiratory Syndrome (SARS) is the first severe and easily transmissible disease to emerge in the 21st century. It is caused by the infection with a coronavirus, a single strand RNA capsulated virus, recently found in a small mammalian, the masked palm civet. It is likely to represent the source of human infection. The first cases of SARS have been reported in the Chinese province of Guangdong and, since then, probable cases have been reported world wide. The clinical picture is characterized by nonspecific symptoms such as fever, cough or dyspnea in patients affected by air-space opacities (unifocal involvement in the 54.6% of cases) or distress respiratory syndrome and linked to a recent exposure to a SARS case or to a travel/residence in an affected area. The empirical therapy is based on broad-spectrum antibiotics, steroids and ribavirin, but susceptibility testing have failed to demonstrate direct anti-viral activity of ribavirin against SARS-related coronavirus in vitro. The exposure to respiratory droplets and the contact with biologic fluids (respiratory and gastrointestinal secretions) represent the most efficient transmission modality of the SARS-related coronavirus. Hand hygiene is the most simple and cost effective measure of infection control to prevent contagion, and the use of airborne, contact and droplet precaution is strictly recommended to all health care workers taking care of such patients. The spread of SARS, to less developed country with limited resource for public health programs, represent the emerging alarming threat in the new global scenario. PMID:12868234

  11. Comparison of laparoscopy and open surgery in treating severe acute pancreatitis and its relative aftercare.

    PubMed

    Zhang, J; Jiang, M X; Zheng, Y; Shu, M; Sun, S B

    2016-01-01

    This study was designed to determine the effects and compare laparoscopic intervention and open surgery in treating severe acute pancreatitis (SAP) and its relative aftercare, to improve the overall treatment of SAP. Ninety patients with SAP were enrolled from the 2nd Affiliated Hospital of Harbin Medical University from 2008 to 2014 and divided into a laparoscopic intervention group (25 cases) and an open surgery group (65 cases). Patients were asked for clinical symptoms, general hospital information, laboratory inspection, imageological examination, local and systemic complications, treatment and outcome. SAP patients’ relevant clinical indicators were compared between the two groups before and after the operation. Results revealed that there was no statistical significance in lesion range and main scoring indexes for reflecting the severity of the disease. For both groups statistical significance was found in blood loss (285.3±79.8 mL vs 362±91.6 mL), intensive care unit (ICU) monitoring time (9.04±6.35 d vs 12.48±8.34 d) and service time of breathing machine (9.47±6.24 d vs 12.98±8.25 d), and the laparoscopic operation group was superior to the open surgery group (p < 0.05). Besides, the laparoscopic operation group was also superior to the open surgery group in demand for main analgesics one week after the operation, as well as for recovery rate and incidence of complications (p < 0.05). Thus, it can be concluded that patients undergoing laparoscopic intervention are less likely to develop pulmonary infection and more likely to be cured in comparison with patients who receive open surgery. In addition, laparoscopic intervention results in less damage, lighter pain and fewer complications compared with open surgery. PMID:27049091

  12. Gut Microbiota in Children Hospitalized with Oedematous and Non-Oedematous Severe Acute Malnutrition in Uganda

    PubMed Central

    Kristensen, Kia Hee Schultz; Wiese, Maria; Rytter, Maren Johanne Heilskov; Özçam, Mustafa; Hansen, Lars Hestbjerg; Namusoke, Hanifa; Friis, Henrik; Nielsen, Dennis Sandris

    2016-01-01

    Background Severe acute malnutrition (SAM) among children remains a major health problem in many developing countries. SAM manifests in both an oedematous and a non-oedematous form, with oedematous malnutrition in its most severe form also known as kwashiorkor. The pathogenesis of both types of malnutrition in children remains largely unknown, but gut microbiota (GM) dysbiosis has recently been linked to oedematous malnutrition. In the present study we aimed to assess whether GM composition differed between Ugandan children suffering from either oedematous or non-oedematous malnutrition. Methodology/Principal Findings As part of an observational study among children hospitalized with SAM aged 6–24 months in Uganda, fecal samples were collected at admission. Total genomic DNA was extracted from fecal samples, and PCR amplification was performed followed by Denaturing Gradient Gel Electrophoresis (DGGE) and tag-encoded 16S rRNA gene-targeted high throughput amplicon sequencing. Alpha and beta diversity measures were determined along with ANOVA mean relative abundance and G-test of independence followed by comparisons between groups. Of the 87 SAM children included, 62% suffered from oedematous malnutrition, 66% were boys and the mean age was 16.1 months. GM composition was found to differ between the two groups of children as determined by DGGE (p = 0.0317) and by high-throughput sequencing, with non-oedematous children having lower GM alpha diversity (p = 0.036). However, beta diversity analysis did not reveal larger differences between the GM of children with oedematous and non-oedematous SAM (ANOSIM analysis, weighted UniFrac, R = -0.0085, p = 0.584; unweighted UniFrac, R = 0.0719, p = 0.011). Conclusions/Significance Our results indicate that non-oedematous SAM children have lower GM diversity compared to oedematous SAM children, however no clear compositional differences were identified. PMID:26771456

  13. Hydrogen-rich saline ameliorates the severity of L-arginine-induced acute pancreatitis in rats

    SciTech Connect

    Chen, Han; Sun, Yan Ping; Li, Yang; Liu, Wen Wu; Xiang, Hong Gang; Fan, Lie Ying; Sun, Qiang; Xu, Xin Yun; Cai, Jian Mei; Ruan, Can Ping; Su, Ning; Yan, Rong Lin; Sun, Xue Jun; Wang, Qiang

    2010-03-05

    Molecular hydrogen, which reacts with the hydroxyl radical, has been considered as a novel antioxidant. Here, we evaluated the protective effects of hydrogen-rich saline on the L-arginine (L-Arg)-induced acute pancreatitis (AP). AP was induced in Sprague-Dawley rats by giving two intraperitoneal injections of L-Arg, each at concentrations of 250 mg/100 g body weight, with an interval of 1 h. Hydrogen-rich saline (>0.6 mM, 6 ml/kg) or saline (6 ml/kg) was administered, respectively, via tail vein 15 min after each L-Arg administration. Severity of AP was assessed by analysis of serum amylase activity, pancreatic water content and histology. Samples of pancreas were taken for measuring malondialdehyde and myeloperoxidase. Apoptosis in pancreatic acinar cell was determined with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique (TUNEL). Expression of proliferating cell nuclear antigen (PCNA) and nuclear factor kappa B (NF-{kappa}B) were detected with immunohistochemistry. Hydrogen-rich saline treatment significantly attenuated the severity of L-Arg-induced AP by ameliorating the increased serum amylase activity, inhibiting neutrophil infiltration, lipid oxidation and pancreatic tissue edema. Moreover, hydrogen-rich saline treatment could promote acinar cell proliferation, inhibit apoptosis and NF-{kappa}B activation. These results indicate that hydrogen treatment has a protective effect against AP, and the effect is possibly due to its ability to inhibit oxidative stress, apoptosis, NF-{kappa}B activation and to promote acinar cell proliferation.

  14. Tumor Necrosis Factor Alpha Promoter Polymorphism and Severity of Acute Kidney Injury

    PubMed Central

    Susantitaphong, Paweena; Perianayagam, Mary C.; Tighiouart, Hocine; Liangos, Orfeas; Bonventre, Joseph V.; Jaber, Bertrand L.

    2016-01-01

    Background Tumor necrosis factor-alpha is a proinflammatory cytokine that has been implicated in the pathobiology of acute kidney injury (AKI). Methods We explored the association of a functional polymorphism in the promoter region (rs1800629) of the TNFA gene with severity of AKI, as defined by level of glomerular filtration (serum cystatin C and creatinine) and tubular injury (urinary NAG, KIM-1, α-GST, and π-GST) markers, in 262 hospitalized adults. Results In unadjusted analyses, compared with the GG genotype, the TNFA GA and AA genotype groups tended to have higher enrollment (p = 0.08), peak (p = 0.004), and discharge (p = 0.004) serum creatinine levels, and the AA genotype tended to have a higher enrollment serum cystatin C level (p = 0.04). Compared with the GG genotype, the TNFA GA and AA genotype groups tended to have a higher urinary KIM-1 level (p = 0.03), and the AA genotype group tended to have a higher urinary π-GST level (p = 0.03). After adjustment for sex, race, age, baseline estimated glomerular filtration rate, sepsis, and dialysis requirement, compared with the GG genotype, the TNFA minor A-allele group had a higher peak serum creatinine of 1.03 mg/dl (0.43, 1.63; p = 0.001) and a higher urinary KIM-1 (relative ratio: 1.73; 95% CI: 1.16, 2.59; p = 0.008). The TNFA minor A-allele group also had a higher Multiple Organ Failure score of 0.26 (95% CI: 0.03, 0.49; p = 0.024) after adjustment for sex, race, age, and sepsis. Conclusions The TNFA rs1800629 gene polymorphism is associated with markers of kidney disease severity and distant organ dysfunction among patients with AKI. Larger studies are needed to confirm these relationships. PMID:23796916

  15. Mesenteric lymph duct drainage attenuates acute lung injury in rats with severe intraperitoneal infection.

    PubMed

    Zhang, Yanmin; Zhang, Shukun; Tsui, Naiqiang

    2015-01-01

    The purpose of this study is to investigate the hypothesis that the mesenteric lymphatic system plays an important role in acute lung injury in a rat model induced by severe intraperitoneal infection. Male Wistar rats weighing 250∼300 g were randomly divided into 3 groups and subjected to sham operation, intraperitoneal infection, or mesenteric lymphatic drainage. The activity of diamine oxidase (DAO) and myeloperoxidase (MPO) were measured by enzymatic assay. The endotoxin levels in plasma, lymph, and bronchoalveolar lavage fluid (BALF) were evaluated using the limulus amoebocyte lysate reagent. The cytokines, adhesion factors, chemokines, and inflammatory factors were detected by ELISA. TLR-4, NF-kB, and IRAK-4 were analyzed by Western blotting. Compared with sham-operated rats, rats with intraperitoneal infection had increased MPO and decreased DAO activity in intestinal tissues. Mesenteric lymph drainage reduced the alterations in MPO and DAO activity induced by intraperitoneal infection. The MPO activity in pulmonary tissue and the permeability of pulmonary blood vessels were also increased, which were partially reversed by mesenteric lymph drainage. The endotoxin levels in lymphatic fluid and alveolar perfusion fluid were elevated after intraperitoneal infection but decreased to control levels after lymph drainage. No alterations in the levels of plasma endotoxin were observed. The number of neutrophils was increased in BALF and lymph in the infected rats, and was also reduced after drainage. Lymph drainage also decreased the levels of inflammatory cytokines, chemokines, and adhesion factors in the plasma, lymph, and BALF, as well as the levels of TLR-4, NF-kB, and IRAK-4 in pulmonary and intestinal tissues. The mesenteric lymphatic system is the main pathway involved in early lung injury caused by severe intraperitoneal infection, in which activation of the TLR-4 signal pathway may play a role. PMID:25537798

  16. Over-the-scope clip placement is effective rescue therapy for severe acute upper gastrointestinal bleeding

    PubMed Central

    Skinner, Matthew; Gutierrez, Juan P.; Neumann, Helmut; Wilcox, C. Mel; Burski, Chad; Mönkemüller, Klaus

    2014-01-01

    Background and study aim: The novel over-the-scope clip (OTSC) allows for excellent apposition of tissue, potentially permitting hemostasis to be achieved in various types of gastrointestinal lesions. This study aimed to evaluate the usefulness and safety of OTSCs for endoscopic hemostasis in patients with upper gastrointestinal bleeding in whom traditional endoscopic methods had failed. Patients and methods: A retrospective case series of all patients who underwent placement of an OTSC for severe recurrent upper gastrointestinal bleeding over a 14-month period was studied. Outcome data for the procedure included achievement of primary hemostasis, episodes of recurrent bleeding, and complications. Results: Twelve consecutive patients (67 % men; mean age 59, range 29 – 86) with ongoing upper gastrointestinal bleeding despite previous endoscopic management were included. They had a mean ASA score of 3 (range 2 – 4), a mean hemoglobin of 7.2 g/dL (range 5.2 – 9.1), and shock was present in 75 % of patients. They had all received packed red blood cells (mean 5.1 units, range 2 – 12). The etiology of bleeding was: duodenal ulcer (n = 6), gastric ulcer (n = 2) Dieulafoy lesion (n = 2), anastomotic ulceration (n = 1), Mallory – Weiss tear (n = 1). Hemostasis was achieved in all patients. Rebleeding occurred in two patients 1 day and 7 days after OTSC placement. There were no complications associated with OTSC application. Conclusions: OTSC use represents an effective, easily performed, and safe endoscopic therapy for various causes of severe acute gastrointestinal bleeding when conventional endoscopic techniques have failed. This therapy should be added to the armamentarium of therapeutic endoscopists. PMID:26134611

  17. One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities.

    PubMed

    Subissi, Lorenzo; Posthuma, Clara C; Collet, Axelle; Zevenhoven-Dobbe, Jessika C; Gorbalenya, Alexander E; Decroly, Etienne; Snijder, Eric J; Canard, Bruno; Imbert, Isabelle

    2014-09-16

    In addition to members causing milder human infections, the Coronaviridae family includes potentially lethal zoonotic agents causing severe acute respiratory syndrome (SARS) and the recently emerged Middle East respiratory syndrome. The ∼30-kb positive-stranded RNA genome of coronaviruses encodes a replication/transcription machinery that is unusually complex and composed of 16 nonstructural proteins (nsps). SARS-CoV nsp12, the canonical RNA-dependent RNA polymerase (RdRp), exhibits poorly processive RNA synthesis in vitro, at odds with the efficient replication of a very large RNA genome in vivo. Here, we report that SARS-CoV nsp7 and nsp8 activate and confer processivity to the RNA-synthesizing activity of nsp12. Using biochemical assays and reverse genetics, the importance of conserved nsp7 and nsp8 residues was probed. Whereas several nsp7 mutations affected virus replication to a limited extent, the replacement of two nsp8 residues (P183 and R190) essential for interaction with nsp12 and a third (K58) critical for the interaction of the polymerase complex with RNA were all lethal to the virus. Without a loss of processivity, the nsp7/nsp8/nsp12 complex can associate with nsp14, a bifunctional enzyme bearing 3'-5' exoribonuclease and RNA cap N7-guanine methyltransferase activities involved in replication fidelity and 5'-RNA capping, respectively. The identification of this tripartite polymerase complex that in turn associates with the nsp14 proofreading enzyme sheds light on how coronaviruses assemble an RNA-synthesizing machinery to replicate the largest known RNA genomes. This protein complex is a fascinating example of the functional integration of RNA polymerase, capping, and proofreading activities. PMID:25197083

  18. One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities

    PubMed Central

    Subissi, Lorenzo; Posthuma, Clara C.; Collet, Axelle; Zevenhoven-Dobbe, Jessika C.; Gorbalenya, Alexander E.; Decroly, Etienne; Snijder, Eric J.; Canard, Bruno; Imbert, Isabelle

    2014-01-01

    In addition to members causing milder human infections, the Coronaviridae family includes potentially lethal zoonotic agents causing severe acute respiratory syndrome (SARS) and the recently emerged Middle East respiratory syndrome. The ∼30-kb positive-stranded RNA genome of coronaviruses encodes a replication/transcription machinery that is unusually complex and composed of 16 nonstructural proteins (nsps). SARS-CoV nsp12, the canonical RNA-dependent RNA polymerase (RdRp), exhibits poorly processive RNA synthesis in vitro, at odds with the efficient replication of a very large RNA genome in vivo. Here, we report that SARS-CoV nsp7 and nsp8 activate and confer processivity to the RNA-synthesizing activity of nsp12. Using biochemical assays and reverse genetics, the importance of conserved nsp7 and nsp8 residues was probed. Whereas several nsp7 mutations affected virus replication to a limited extent, the replacement of two nsp8 residues (P183 and R190) essential for interaction with nsp12 and a third (K58) critical for the interaction of the polymerase complex with RNA were all lethal to the virus. Without a loss of processivity, the nsp7/nsp8/nsp12 complex can associate with nsp14, a bifunctional enzyme bearing 3′-5′ exoribonuclease and RNA cap N7-guanine methyltransferase activities involved in replication fidelity and 5′-RNA capping, respectively. The identification of this tripartite polymerase complex that in turn associates with the nsp14 proofreading enzyme sheds light on how coronaviruses assemble an RNA-synthesizing machinery to replicate the largest known RNA genomes. This protein complex is a fascinating example of the functional integration of RNA polymerase, capping, and proofreading activities. PMID:25197083

  19. Abdominal Muscle Activity during Mechanical Ventilation Increases Lung Injury in Severe Acute Respiratory Distress Syndrome

    PubMed Central

    Zhang, Xianming; Wu, Weiliang; Zhu, Yongcheng; Jiang, Ying; Du, Juan; Chen, Rongchang

    2016-01-01

    Objective It has proved that muscle paralysis was more protective for injured lung in severe acute respiratory distress syndrome (ARDS), but the precise mechanism is not clear. The purpose of this study was to test the hypothesis that abdominal muscle activity during mechanically ventilation increases lung injury in severe ARDS. Methods Eighteen male Beagles were studied under mechanical ventilation with anesthesia. Severe ARDS was induced by repetitive oleic acid infusion. After lung injury, Beagles were randomly assigned into spontaneous breathing group (BIPAPSB) and abdominal muscle paralysis group (BIPAPAP). All groups were ventilated with BIPAP model for 8h, and the high pressure titrated to reached a tidal volume of 6ml/kg, the low pressure was set at 10 cmH2O, with I:E ratio 1:1, and respiratory rate adjusted to a PaCO2 of 35–60 mmHg. Six Beagles without ventilator support comprised the control group. Respiratory variables, end-expiratory volume (EELV) and gas exchange were assessed during mechanical ventilation. The levels of Interleukin (IL)-6, IL-8 in lung tissue and plasma were measured by qRT-PCR and ELISA respectively. Lung injury scores were determined at end of the experiment. Results For the comparable ventilator setting, as compared with BIPAPSB group, the BIPAPAP group presented higher EELV (427±47 vs. 366±38 ml) and oxygenation index (293±36 vs. 226±31 mmHg), lower levels of IL-6(216.6±48.0 vs. 297.5±71.2 pg/ml) and IL-8(246.8±78.2 vs. 357.5±69.3 pg/ml) in plasma, and lower express levels of IL-6 mRNA (15.0±3.8 vs. 21.2±3.7) and IL-8 mRNA (18.9±6.8 vs. 29.5±7.9) in lung tissues. In addition, less lung histopathology injury were revealed in the BIPAPAP group (22.5±2.0 vs. 25.2±2.1). Conclusion Abdominal muscle activity during mechanically ventilation is one of the injurious factors in severe ARDS, so abdominal muscle paralysis might be an effective strategy to minimize ventilator-induce lung injury. PMID:26745868

  20. Influence of Pneumococcal Conjugate Vaccine on Acute Otitis Media with Severe Middle Ear Inflammation: A Retrospective Multicenter Study

    PubMed Central

    Sugino, Hirotoshi; Tsumura, Shigeru; Kunimoto, Masaru; Noda, Masuhiro; Chikuie, Daisuke; Noda, Chieko; Yamashita, Mariko; Watanabe, Hiroshi; Ishii, Hidemasa; Tashiro, Toru; Iwata, Kazuhiro; Kono, Takashi; Tsumura, Kaoru; Sumiya, Takahiro; Takeno, Sachio; Hirakawa, Katsuhiro

    2015-01-01

    The Japanese guidelines for acute otitis media in children recommend classifying acute otitis media by age, manifestations and local findings, and also recommend myringotomy for moderate-grade cases with severe local findings, severe-grade cases, and treatment-resistant cases. The heptavalent pneumococcal conjugate vaccine was released in Japan in February 2010. In Hiroshima City, public funding allowing free inoculation with this vaccine was initiated from January 2011, and the number of vaccinated individuals has since increased dramatically. This study investigated changes in the number of myringotomies performed to treat acute otitis media during the 5-year period from January 2008 to December 2012 at two hospitals and five clinics in the Asa Area of Hiroshima City, Japan. A total of 3,165 myringotomies for acute otitis media were performed. The rate of procedures per child-year performed in <5-year-old children decreased by 29.1% in 2011 and by 25.2% in 2012 compared to the mean rate performed in the 3 years prior to the introduction of public funding. A total of 895 myringotomies were performed for 1-year-old infants. The rate of myringotomies per child-year performed for acute otitis media in 1-year-old infants decreased significantly in the 2 years after the introduction of public funding for heptavalent pneumococcal conjugate vaccine compared to all years before introduction (p<0.000001). Our results suggest a benefit of heptavalent pneumococcal conjugate vaccine for acute otitis media in reducing the financial burden of myringotomy. In addition, this vaccine may help prevent acute otitis media with severe middle ear inflammation in 1-year-old infants. PMID:26348230

  1. Role of Inhaled Nitric Oxide in the Management of Severe Acute Respiratory Distress Syndrome

    PubMed Central

    Hunt, Juliette Lucinda; Bronicki, Ronald A.; Anas, Nick

    2016-01-01

    To date, there have been several systematic reviews with meta-analysis that have shown no reduction in mortality with the use of inhaled nitric oxide (iNO) in patients with acute respiratory distress syndrome (ARDS). Importantly, these reports fail to make a distinction between the pediatric and adult patient. The number of adult patients in these reviews are far greater than the number of pediatric patients, which makes it difficult to interpret the data regarding the role of iNO on the pediatric population. Extrapolating data from the adult population to the pediatric population is complicated as we know that physiology and the body’s response to disease can be different between adult and pediatric patients. iNO has been demonstrated to improve outcomes in term and near-term infants with hypoxic respiratory failure associated with pulmonary hypertension. Recently, Bronicki et al. published a prospective randomized control trial investigating the impact of iNO on the pediatric patient population with acute respiratory failure. In this study, a benefit of decreased duration of mechanical ventilation and an increased rate of ECMO-free survival was demonstrated in patients who were randomized to receiving iNO, suggesting that there may be benefit to the use of iNO in pediatric ARDS (PARDS) that has not been demonstrated in adults. iNO has repeatedly been shown to transiently improve oxygenation in all age groups, and yet neonates and pediatric patients have shown improvement in other outcomes that have not been seen in adults. The mechanism that explains improvement with the use of iNO in these patient populations are not well understood but does not appear to be solely a result of sustained improvement in oxygenation. There are physiologic studies that suggest alternative mechanisms for explaining the positive effects of iNO, such as platelet aggregation inhibition and reduction in systemic inflammation. Hence, the role of iNO by various mechanisms and in various

  2. Severe starvation-induced hepatocyte autophagy as a cause of acute liver injury in anorexia nervosa: a case report.

    PubMed

    Restellini, S; Spahr, L; Rubbia Brandt, L

    2013-01-01

    Introduction. Mild elevation of transaminase may be observed in anorexia nervosa, but acute liver injury is uncommon. A complex programmed cell death in response to starvation, called autophagy, has been described in experimental and human studies. Case Presentation. A 24-year-old woman suffering from anorexia nervosa was hospitalized for severe malnutrition. At admission, there were biological signs of acute liver injury but no electrolytic imbalance. After having ruled out the most common causes of liver injury, the patient was carefully refed. As liver tests remained abnormal, liver biopsy was performed. At histology and electron microscopy, numerous signs suggestive of starvation-induced hepatocyte autophagy were found. Discussion. Severe starvation can be associated with acute liver injury that is slowly reversible with careful enteral nutrition. In this clinical situation, profound hepatic glycogen depletion in association with autophagy appears as the leading cause of liver injury. PMID:25379300

  3. Metabolite Modulation in Human Plasma in the Early Phase of Acclimatization to Hypobaric Hypoxia

    PubMed Central

    Liao, Wen-Ting; Liu, Bao; Chen, Jian; Cui, Jian-Hua; Gao, Yi-Xing; Liu, Fu-Yu; Xu, Gang; Sun, Bing-Da; Zhang, Er-Long; Yuan, Zhi-Bin; Zhang, Gang; Gao, Yu-Qi

    2016-01-01

    The exposure of healthy subjects to high altitude represents a model to explore the pathophysiology of diseases related to tissue hypoxia. We explored a plasma metabolomics approach to detect alterations induced by the exposure of subjects to high altitude. Plasma samples were collected from 60 subjects both on plain and at high altitude (5300 m). Metabolite profiling was performed by gas chromatography-mass spectrometry (GC-MS) and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS) in conjunction with univariate and multivariate statistical analyses. ELISA assays were further employed to measure the levels of several relevant enzymes together with perturbed metabolic pathways. The results showed that hypobaric hypoxia caused significant and comprehensive metabolic changes, as represented by significant changes of 44 metabolites and 4 relevant enzymes. Using MetaboAnalyst 3.0, it was found that several key metabolic pathways were acutely perturbed. In addition, 5 differentially expressed metabolites in pre-exposure samples from the acute mountain sickness-susceptible (AMS-S) group compared with those from the AMS-resistant (AMS-R) group are identified, which warrant further validation as potential predictive biomarkers for AMS-S individuals. These results provide new insights for further understanding the pathophysiological mechanism of early acclimatization to hypobaric hypoxia and other diseases correlated to tissue hypoxia. PMID:26940428

  4. Epidural anesthesia improves pancreatic perfusion and decreases the severity of acute pancreatitis

    PubMed Central

    Sadowski, Samira M; Andres, Axel; Morel, Philippe; Schiffer, Eduardo; Frossard, Jean-Louis; Platon, Alexandra; Poletti, Pierre-Alexandre; Bühler, Leo

    2015-01-01

    AIM: To study the safety of epidural anesthesia (EA), its effect on pancreatic perfusion and the outcome of patients with acute pancreatitis (AP). METHODS: From 2005 to August 2010, patients with predicted severe AP [Ranson score ≥ 2, C-reactive protein > 100 or necrosis on computed tomography (CT)] were prospectively randomized to either a group receiving EA or a control group treated by patient controlled intravenous analgesia. Pain management was evaluated in the two groups every eight hours using the visual analog pain scale (VAS). Parameters for clinical severity such as length of hospital stay, use of antibiotics, admission to the intensive care unit, radiological/clinical complications and the need for surgical necrosectomy including biochemical data were recorded. A CT scan using a perfusion protocol was performed on admission and at 72 h to evaluate pancreatic blood flow. A significant variation in blood flow was defined as a 20% difference in pancreatic perfusion between admission and 72 h and was measured in the head, body and tail of the pancreas. RESULTS: We enrolled 35 patients. Thirteen were randomized to the EA group and 22 to the control group. There were no differences in demographic characteristics between the two groups. The Balthazar radiological severity score on admission was higher in the EA group than in the control group (mean score 4.15 ± 2.54 vs 3.38 ± 1.75, respectively, P = 0.347) and the median Ranson scores were 3.4 and 2.7 respectively (P = NS). The median duration of EA was 5.7 d, and no complications of the epidural procedure were reported. An improvement in perfusion of the pancreas was observed in 13/30 (43%) of measurements in the EA group vs 2/27 (7%) in the control group (P = 0.0025). Necrosectomy was performed in 1/13 patients in the EA group vs 4/22 patients in the control group (P = 0.63). The VAS improved during the first ten days in the EA group compared to the control group (0.2 vs 2.33, P = 0.034 at 10 d). Length

  5. Characterization and Predictive Value of Near Infrared 2-Deoxyglucose Optical Imaging in Severe Acute Pancreatitis

    PubMed Central

    de Oliveira, Cristiane; Patel, Krutika; Mishra, Vivek; Trivedi, Ram N.; Noel, Pawan; Singh, Abhilasha; Yaron, Jordan R.; Singh, Vijay P.

    2016-01-01

    Background Studying the uptake of 2-deoxy glucose (2-DG) analogs such as 2-Deoxy-2-[18F] fluoroglucose (FDG) is a common approach to identify and monitor malignancies and more recently chronic inflammation. While pancreatitis is a common cause for false positive results in human studies on pancreatic cancer using FDG, the relevance of these findings to acute pancreatitis (AP) is unknown. FDG has a short half-life. Thus, with an aim to accurately characterize the metabolic demand of the pancreas during AP in real-time, we studied the uptake of the non-radioactive, near infrared fluorescence labelled 2-deoxyglucose analog, IRDye® 800CW 2-DG probe (NIR 2-DG; Li-Cor) during mild and severe biliary AP. Methods Wistar rats (300 g; 8–12/group) were administered NIR 2-DG (10 nM; I.V.). Mild and severe biliary AP were respectively induced by biliopancreatic duct ligation (DL) alone or along with infusing glyceryl trilinoleate (GTL; 50 μL/100 g) within 10 minutes of giving NIR 2-DG. Controls (CON) only received NIR 2-DG. Imaging was done every 5–10 minutes over 3 hrs. Average Radiant Efficiency [p/s/cm²/sr]/[μW/cm²] was measured over the pancreas using the IVIS 200 in-vivo imaging system (PerkinElmer) using the Living Image® software and verified in ex vivo pancreata. Blood amylase, lipase and pancreatic edema, necrosis were measured over the course of AP. Results NIR 2-DG uptake over the first hour was not influenced by AP induction. However, while the signal declined in controls and rats with mild AP, there was significantly higher retention of NIR 2-DG in the pancreas after 1 hour in those with GTL pancreatitis. The increase was > 3 fold over controls in the GTL group and was verified to be in the pancreas ex vivo. In vitro, pancreatic acini exposed to GTL had a similar increase in NIR 2-DG uptake which was followed by progressively worse acinar necrosis. Greater retention of NIR 2-DG in vivo was associated with worse pancreatic necrosis, reduced ATP

  6. Unexpectedly Severe Acute Radiotherapy Side Effects Are Associated With Single Nucleotide Polymorphisms of the Melanocortin-1 Receptor

    SciTech Connect

    Fogarty, Gerald B.; Muddle, Rory; Sprung, Carl N.

    2010-08-01

    Purpose: The melanocortin-1 receptor (MC1R) regulates melanin biogenesis. Deoxyribonucleic acid sequence variants in the form of single nucleotide polymorphisms (SNPs) of MC1R affect melanin expression and are linked to skin phenotype. We aimed to determine whether SNPs of MC1R were associated with unexpectedly severe ionizing radiation reactions. Methods and Materials: The MC1R genotype of a cohort of Australians with unexpectedly severe acute and/or late reactions (Common Terminology Criteria Version 3 (CTCv3) Grade 3 or 4) to radiotherapy (RT) for cancer (n = 30) was analyzed. The findings were compared with control data from our previous study of MC1R representative of the general Australian population (n = 1,787). Results: The difference in frequency of alleles encoding a 'red hair color' phenotype in the cohort of patients with unexpectedly severe acute radiation reactions (n = 12) was significantly increased compared with the control population (p = 0.003). Acute radiosensitivity was especially associated with the R160W variant allele (odds ratio, 3.64 [95% confidence interval, 1.3-10.27]). The corresponding comparison of MC1R controls with unexpectedly severe late radiation reactions (n = 18) was not significant. It was also found that R160W as a part of the genotype in the patients with unexpectedly severe acute RT side effects as compared with the control group was also significant (p = 0.043). Conclusions: In this small cohort of cancer patients, deoxyribonucleic acid sequence variants of the MC1R gene, especially the R160W variant, have been associated with unexpectedly severe acute reactions to RT. This result needs to be verified in a larger cohort of patients.

  7. DO ACUTE PHASE PROTEINS REFLECT SEVERITY OF INFLAMMATION IN RAT MODELS OF POLLUTANT-INDUCED LUNG INJURY?

    EPA Science Inventory

    Title: DO ACUTE PHASE PROTEINS REFLECT THE SEVERITY OF INFLAMMATION IN RAT MODELS OF POLLUTANT-INDUCED LUNG INJURY?

    M. C. Schladweiler, BS 1, P. S. Gilmour, PhD 2, D. L. Andrews, BS 1, D. L. Costa, ScD 1, A. D. Ledbetter, BS 1, K. E. Pinkerton, PhD 3 and U. P. Kodavanti, ...

  8. Dietary cysteine is used more efficiently by children with severe acute malnutrition with edema compared with those without edema

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Children with edematous severe acute malnutrition (SAM) produce less cysteine than do their nonedematous counterparts. They also have marked glutathione (GSH) depletion, hair loss, skin erosion, gut mucosal atrophy, and depletion of mucins. Because GSH, skin, hair, mucosal, and mucin proteins are ri...

  9. Evaluation of the routine use of amoxicillin as part of the home-based treatment of severe acute malnutrition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To determine whether the inclusion of amoxicillin correlates with better recovery rates in the home-based treatment of severe acute malnutrition with ready-to-use therapeutic food. This retrospective cohort study compared data from the treatment of two groups of children in Malawi aged 6-59 months w...

  10. Nutritional repletion of children with severe acute malnutrition does not affect VLDL apolipoprotein B-100 synthesis rate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    VLDL apo B-100 is essential for the secretion of liver fat. It is thought that synthesis of this lipoprotein is impaired in childhood severe acute malnutrition (SAM), especially in the edematous syndromes, and that this contributes to the common occurrence of hepatic steatosis in this condition. How...

  11. Review of the safety and efficacy of vitamin A supplementation in the treatment of children with severe acute malnutrition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    World Health Organization (WHO) guidelines recommend for children with severe acute malnutrition (SAM), high-dose vitamin A (VA) supplements be given on day 1 of admission, and on days 2 and 14 in the case of clinical signs of vitamin A deficiency (VAD). Daily low-dose VA follows, delivered in a pre...

  12. Dietary supplementation with aromatic amino acids increases protein synthesis in children wHh severe acute malnutrition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although 2 earlier studies reported that aromatic amino acid (AAA) supplementation of children with severe acute malnutrition (SAM) improved whole-body protein anabolism during the early postadmission (maintenance) phase of rehabilitation, it is not known whether this positive effect was maintained ...

  13. Diastolic dysfunction precedes hypoxia-induced mortality in dystrophic mice

    PubMed Central

    Townsend, DeWayne

    2015-01-01

    Duchenne muscular dystrophy (DMD) is a progressive striated muscle disease that is characterized by skeletal muscle weakness with progressive respiratory and cardiac failure. Together respiratory and cardiac disease account for the majority of mortality in the DMD patient population. However, little is known regarding the effects of respiratory dysfunction on the dystrophic heart. The studies described here examine the effects of acute hypoxia on cardiac function. These studies demonstrate, for the first time, that a mouse model of DMD displays significant mortality following acute exposure to hypoxia. This mortality is characterized by a steady decline in systolic function. Retrospective analysis reveals that significant decreases in diastolic dysfunction, especially in the right ventricle, precede the decline in systolic pressure. The initial hemodynamic response to acute hypoxia in the mouse is similar to that observed in larger species, with significant increases in right ventricular afterload and decreases in left ventricular preload being observed. Significant increases in heart rate and contractility suggest hypoxia-induced activation of the sympathetic nervous system. These studies provide evidence that while hypoxia presents significant hemodynamic challenges to the dystrophic right ventricle, global cardiac dysfunction precedes hypoxia-induced mortality in the dystrophic heart. These findings are clinically relevant as the respiratory insufficiency evident in patients with DMD results in significant bouts of hypoxia. The results of these studies indicate that hypoxia may contribute to the acceleration of the heart disease in DMD patients. Importantly, hypoxia can be avoided through the use of ventilatory support. PMID:26311833

  14. The prognostic value of pulmonary embolism severity index in acute pulmonary embolism: a meta-analysis

    PubMed Central

    2012-01-01

    Background Prognostic assessment is important for the management of patients with acute pulmonary embolism (APE). Pulmonary Embolism Severity Index (PESI) and simple PESI (sPESI) are new emerged prognostic assessment tools for APE. The aim of this meta-analysis is to assess the accuracy of the PESI and the sPESI to predict prognostic outcomes (all-cause and PE-related mortality, serious adverse events) in APE patients, and compare between these two PESIs. Methods MEDLINE and EMBASE database were searched up to June 2012 using the terms “Pulmonary Embolism Severity Index” and “pulmonary embolism”. Summary odds ratio (OR) with 95% confidence intervals (CIs) for prognostic outcomes in low risk PESI versus high risk PESI were calculated. Summary receiver operating characteristic curve (SROC) used to estimate overall predicting accuracies of prognostic outcomes. Results Twenty-one studies were included in this meta-analysis. The results showed low-risk PESI was significantly associated with lower all-cause mortality (OR 0.13; 95% CI 0.12 to 0.15), PE-related mortality (OR 0.09; 95% CI 0.05 to 0.17) and serious adverse events (OR 0.34; 95% CI 0.29 to 0.41), with no homogeneity across studies. In sPESI subgroup, the OR of all-cause mortality, PE-related mortality, and serious adverse events was 0.10 (95% CI 0.08 to 0.14), 0.09 (95% CI 0.03 to 0.26) and 0.40 (95% CI 0.31 to 0.51), respectively; while in PESI subgroup, the OR was 0.14 (95% CI 0.13 to 0.16), 0.09 (95% CI 0.04 to 0.21), and 0.30 (95% CI 0.23 to 0.38), respectively. For accuracy analysis, the pooled sensitivity, the pooled specificity, and the overall weighted AUC for PESI predicting all-cause mortality was 0.909 (95% CI: 0.900 to 0.916), 0.411 (95% CI: 0.407 to 0.415), and 0.7853±0.0058, respectively; for PE-related mortality, it was 0.953 (95% CI: 0.913 to 0.978), 0.374 (95% CI: 0.360 to 0.388), and 0.8218±0.0349, respectively; for serious adverse events, it was 0.821 (95% CI: 0.795 to 0.845), 0

  15. Gut DNA viromes of Malawian twins discordant for severe acute malnutrition.

    PubMed

    Reyes, Alejandro; Blanton, Laura V; Cao, Song; Zhao, Guoyan; Manary, Mark; Trehan, Indi; Smith, Michelle I; Wang, David; Virgin, Herbert W; Rohwer, Forest; Gordon, Jeffrey I

    2015-09-22

    The bacterial component of the human gut microbiota undergoes a definable program of postnatal development. Evidence is accumulating that this program is disrupted in children with severe acute malnutrition (SAM) and that their persistent gut microbiota immaturity, which is not durably repaired with current ready-to-use therapeutic food (RUTF) interventions, is causally related to disease pathogenesis. To further characterize gut microbial community development in healthy versus malnourished infants/children, we performed a time-series metagenomic study of DNA isolated from virus-like particles (VLPs) recovered from fecal samples collected during the first 30 mo of postnatal life from eight pairs of mono- and dizygotic Malawian twins concordant for healthy growth and 12 twin pairs discordant for SAM. Both members of discordant pairs were sampled just before, during, and after treatment with a peanut-based RUTF. Using Random Forests and a dataset of 17,676 viral contigs assembled from shotgun sequencing reads of VLP DNAs, we identified viruses that distinguish different stages in the assembly of the gut microbiota in the concordant healthy twin pairs. This developmental program is impaired in both members of SAM discordant pairs and not repaired with RUTF. Phage plus members of the Anelloviridae and Circoviridae families of eukaryotic viruses discriminate discordant from concordant healthy pairs. These results disclose that apparently healthy cotwins in discordant pairs have viromes associated with, although not necessarily mediators, of SAM; as such, they provide a human model for delineating normal versus perturbed postnatal acquisition and retention of the gut microbiota's viral component in populations at risk for malnutrition. PMID:26351661

  16. Infections in Children Admitted with Complicated Severe Acute Malnutrition in Niger

    PubMed Central

    Page, Anne-Laure; de Rekeneire, Nathalie; Sayadi, Sani; Aberrane, Said; Janssens, Ann-Carole; Rieux, Claire; Djibo, Ali; Manuguerra, Jean-Claude; Ducou-le-Pointe, Hubert; Grais, Rebecca F.; Schaefer, Myrto; Guerin, Philippe J.; Baron, Emmanuel

    2013-01-01

    Background Although malnutrition affects thousands of children throughout the Sahel each year and predisposes them to infections, there is little data on the etiology of infections in these populations. We present a clinical and biological characterization of infections in hospitalized children with complicated severe acute malnutrition (SAM) in Maradi, Niger. Methods Children with complicated SAM hospitalized in the intensive care unit of a therapeutic feeding center, with no antibiotics in the previous 7 days, were included. A clinical examination, blood, urine and stool cultures, and chest radiography were performed systematically on admission. Results Among the 311 children included in the study, gastroenteritis was the most frequent clinical diagnosis on admission, followed by respiratory tract infections and malaria. Blood or urine culture was positive in 17% and 16% of cases, respectively, and 36% had abnormal chest radiography. Enterobacteria were sensitive to most antibiotics, except amoxicillin and cotrimoxazole. Twenty-nine (9%) children died, most frequently from sepsis. Clinical signs were poor indicators of infection and initial diagnoses correlated poorly with biologically or radiography-confirmed diagnoses. Conclusions These data confirm the high level of infections and poor correlation with clinical signs in children with complicated SAM, and provide antibiotic resistance profiles from an area with limited microbiological data. These results contribute unique data to the ongoing debate on the use and choice of broad-spectrum antibiotics as first-line treatment in children with complicated SAM and reinforce the call for an update of international guidelines on management of complicated SAM based on more recent data. PMID:23874731

  17. Changes in whole-blood PUFA and their predictors during recovery from severe acute malnutrition.

    PubMed

    Babirekere-Iriso, Esther; Mortensen, Charlotte G; Mupere, Ezekiel; Rytter, Maren J H; Namusoke, Hanifa; Michaelsen, Kim F; Briend, André; Stark, Ken D; Friis, Henrik; Lauritzen, Lotte

    2016-05-01

    Children with severe acute malnutrition (SAM) with complications require in-patient management including therapeutic feeding. Little attention has been given to the effects of these feeds on the essential fatty acid status of children with SAM. The objective of this study was to describe changes in the PUFA composition in whole blood in children with SAM during treatment and to determine predictors of change. This prospective study took place in a paediatric nutrition rehabilitation unit in Kampala, Uganda, and assessed whole-blood fatty acid composition of children with SAM at admission, transition, discharge and follow-up (8 and 16 weeks). ANCOVA was used to identify predictors of change in whole-blood PUFA. The study included 120 children with SAM and twenty-nine healthy control children of similar age and sex. Among the SAM children, 38 % were female and 64 % had oedema. Whole-blood n-6 PUFA proportions increased from admission to follow-up, except for arachidonic acid, which decreased by 0·79 (95 % CI 0·46, 1·12) fatty acid percentage (FA%) from admission to transition and 0·10 (95 % CI 0·23, 0·44) FA% at discharge. n-3 Long-chain (LC) PUFA decreased by 0·21 (95 % CI 0·03, 0·40) FA% at discharge and 0·22 (95 % CI 0·01, 0·42) FA% at 8 weeks of follow-up. This decrease was greater in children from families with recent fish intake and those with nasogastric tube feeding. Current therapeutic feeds do not correct whole-blood levels of LCPUFA, particularly n-3 LCPUFA, in children with SAM. Increased attention is needed to the contents of n-3 LCPUFA in therapeutic feeds. PMID:26996197

  18. Gut DNA viromes of Malawian twins discordant for severe acute malnutrition

    PubMed Central

    Reyes, Alejandro; Blanton, Laura V.; Cao, Song; Zhao, Guoyan; Manary, Mark; Trehan, Indi; Smith, Michelle I.; Wang, David; Virgin, Herbert W.; Rohwer, Forest; Gordon, Jeffrey I.

    2015-01-01

    The bacterial component of the human gut microbiota undergoes a definable program of postnatal development. Evidence is accumulating that this program is disrupted in children with severe acute malnutrition (SAM) and that their persistent gut microbiota immaturity, which is not durably repaired with current ready-to-use therapeutic food (RUTF) interventions, is causally related to disease pathogenesis. To further characterize gut microbial community development in healthy versus malnourished infants/children, we performed a time-series metagenomic study of DNA isolated from virus-like particles (VLPs) recovered from fecal samples collected during the first 30 mo of postnatal life from eight pairs of mono- and dizygotic Malawian twins concordant for healthy growth and 12 twin pairs discordant for SAM. Both members of discordant pairs were sampled just before, during, and after treatment with a peanut-based RUTF. Using Random Forests and a dataset of 17,676 viral contigs assembled from shotgun sequencing reads of VLP DNAs, we identified viruses that distinguish different stages in the assembly of the gut microbiota in the concordant healthy twin pairs. This developmental program is impaired in both members of SAM discordant pairs and not repaired with RUTF. Phage plus members of the Anelloviridae and Circoviridae families of eukaryotic viruses discriminate discordant from concordant healthy pairs. These results disclose that apparently healthy cotwins in discordant pairs have viromes associated with, although not necessarily mediators, of SAM; as such, they provide a human model for delineating normal versus perturbed postnatal acquisition and retention of the gut microbiota’s viral component in populations at risk for malnutrition. PMID:26351661

  19. Effects of early enteral nutrition on immune function of severe acute pancreatitis patients

    PubMed Central

    Sun, Jia-Kui; Mu, Xin-Wei; Li, Wei-Qin; Tong, Zhi-Hui; Li, Jing; Zheng, Shu-Yun

    2013-01-01

    AIM: To investigate the effects of early enteral nutrition (EEN) on the immune function and clinical outcome of patients with severe acute pancreatitis (SAP). METHODS: Patients were randomly allocated to receive EEN or delayed enteral nutrition (DEN). Enteral nutrition was started within 48 h after admission in EEN group, whereas from the 8th day in DEN group. All the immunologic parameters and C-reactive protein (CRP) levels were collected on days 1, 3, 7 and 14 after admission. The clinical outcome variables were also recorded. RESULTS: Sixty SAP patients were enrolled to this study. The CD4+ T-lymphocyte percentage, CD4+/CD8+ ratio, and the CRP levels in EEN group became significantly lower than in DEN group from the 7th day after admission. In contrast, the immunoglobulin G (IgG) levels and human leukocyte antigen-DR expression in EEN group became significantly higher than in DEN group from the 7th day after admission. No difference of CD8+ T-lymphocyte percentage, IgM and IgA levels was found between the two groups. The incidences of multiple organ dysfunction syndrome, systemic inflammatory response syndrome, and pancreatic infection as well as the duration of intensive care unit stay were significantly lower in EEN group than in DEN group. However, there was no difference of hospital mortality between the two groups. CONCLUSION: EEN moderates the excessive immune response during the early stage of SAP without leading to subsequent immunosuppression. EEN can improve the clinical outcome, but not decrease the hospital mortality of SAP patients. PMID:23431120

  20. Mechanisms of Host Receptor Adaptation by Severe Acute Respiratory Syndrome Coronavirus

    SciTech Connect

    Wu, Kailang; Peng, Guiqing; Wilken, Matthew; Geraghty, Robert J.; Li, Fang

    2012-12-10

    The severe acute respiratory syndrome coronavirus (SARS-CoV) from palm civets has twice evolved the capacity to infect humans by gaining binding affinity for human receptor angiotensin-converting enzyme 2 (ACE2). Numerous mutations have been identified in the receptor-binding domain (RBD) of different SARS-CoV strains isolated from humans or civets. Why these mutations were naturally selected or how SARS-CoV evolved to adapt to different host receptors has been poorly understood, presenting evolutionary and epidemic conundrums. In this study, we investigated the impact of these mutations on receptor recognition, an important determinant of SARS-CoV infection and pathogenesis. Using a combination of biochemical, functional, and crystallographic approaches, we elucidated the molecular and structural mechanisms of each of these naturally selected RBD mutations. These mutations either strengthen favorable interactions or reduce unfavorable interactions with two virus-binding hot spots on ACE2, and by doing so, they enhance viral interactions with either human (hACE2) or civet (cACE2) ACE2. Therefore, these mutations were viral adaptations to either hACE2 or cACE2. To corroborate the above analysis, we designed and characterized two optimized RBDs. The human-optimized RBD contains all of the hACE2-adapted residues (Phe-442, Phe-472, Asn-479, Asp-480, and Thr-487) and possesses exceptionally high affinity for hACE2 but relative low affinity for cACE2. The civet-optimized RBD contains all of the cACE2-adapted residues (Tyr-442, Pro-472, Arg-479, Gly-480, and Thr-487) and possesses exceptionally high affinity for cACE2 and also substantial affinity for hACE2. These results not only illustrate the detailed mechanisms of host receptor adaptation by SARS-CoV but also provide a molecular and structural basis for tracking future SARS-CoV evolution in animals.

  1. Outcomes following sonothrombolysis in severe acute ischemic stroke:subgroup analysis of the CLOTBUST trial

    PubMed Central

    Barlinn, Kristian; Tsivgoulis, Georgios; Barreto, Andrew D; Alleman, John; Molina, Carlos A; Mikulik, Robert; Saqqur, Maher; Demchuk, Andrew M; Schellinger, Peter D; Howard, George; Alexandrov, Andrei V.

    2014-01-01

    Background Sonothrombolysis is safe and may increase the likelihood of early recanalization in acute ischemic stroke (AIS) patients Aims In preparation of a phase III clinical trial, we contrast the likelihood of achieving a sustained recanalization and functional independence in a post-hoc subgroup analysis of patients randomized to transcranial Doppler monitoring plus intravenous (IV) tPA (sonothrombolysis) compared to IV tPA alone in the CLOTBUST trial Methods We analyzed the data from all randomized AIS patients with pre-treatment NIHSS scores ≥10 points and proximal intracranial occlusions in the CLOTBUST trial. We compared sustained complete recanalization rate (TIBI flow grades 4-5) and functional independence (modified Rankin Scale [mRS] 0-1) at 90 days. Safety was evaluated by the rate of symptomatic intracranial hemorrhage (ICH) within 72 hours of stroke-onset Results Of 126 patients, a total of 85 AIS patients met our inclusion criteria: mean age 71±11years, 56% men, median NIHSS 17 (interquartile range 14-20). Of these patients, 41 (48%) and 44 (52%) were randomized to IV tPA alone and sonothrombolysis, respectively. More patients achieved sustained complete recanalization in the sonothrombolysis than in the IV tPA alone group (38.6% vs. 17.1%; p=0.032). Functional independence at 90 days was more frequently achieved in the sonothrombolysis than in the IV tPA alone group (37.2% vs. 15.8%; p=0.045). Symptomatic ICH rate was similar in both groups (4.9% vs. 4.6%; p=1.00) Conclusions Our results point to a signal of efficacy and provide information to guide the subsequent phase III randomized trial of sonothrombolysis in patients with severe ischemic strokes PMID:25079049

  2. Predicting Outcome in Acute Organophosphorus Poisoning with a Poison Severity Score or the Glasgow Coma Scale

    PubMed Central

    Davies, James O. J.; Eddleston, Michael; Buckley, Nick A.

    2008-01-01

    Background: Organophosphorus pesticide poisoning kills around 200,000 people each year, principally due to self poisoning in the Asia-Pacific region. Aim: We wished to assess whether patients at high risk of death could be identified accurately using clinical parameters soon after hospital admission. Design: We evaluated the usefulness of the International Program on Chemical Safety Poison Severity Score (IPCS PSS) and the Glasgow Coma Score (GCS) prospectively for predicting death in patients poisoned by organophosphorus pesticides. Methods: Data were collected as part of a multicentre cohort study in Sri Lanka. Study doctors saw all patients on admission, collecting data on pulse, blood pressure, pupil size, need for intubation, and GCS. Results: 1365 patients with a history of acute organophosphorus poisoning were included. Receiver operating characteristic (ROC) curves were calculated for the IPCS PSS and GCS on admission. The IPCS PSS and GCS had similar ROC area under the curves (AUC) and best cut points as determined by Youden's index (AUC/sensitivity/specificity 0.81/0.78/0.79 for IPCS PSS ≥ grade 2 and 0.84/0.79/0.79 for GCS ≤13). The predictive value varied with the pesticide ingested, being more accurate for dimethoate poisoning and less accurate for fenthion poisoning (GCS AUC 0.91 compared to 0.69). Conclusions: GCS and the IPCS PSS were similarly effective at predicting outcome. Patients presenting with a GCS ≤ 13 need intensive monitoring and treatment. However, the identity of the organophosphate must be taken into account since the half of all patients who died from fenthion poisoning only had mild symptoms at presentation. PMID:18319295

  3. Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats

    PubMed Central

    Lau, Susanna K. P.; Woo, Patrick C. Y.; Li, Kenneth S. M.; Huang, Yi; Tsoi, Hoi-Wah; Wong, Beatrice H. L.; Wong, Samson S. Y.; Leung, Suet-Yi; Chan, Kwok-Hung; Yuen, Kwok-Yung

    2005-01-01

    Although the finding of severe acute respiratory syndrome coronavirus (SARS-CoV) in caged palm civets from live animal markets in China has provided evidence for interspecies transmission in the genesis of the SARS epidemic, subsequent studies suggested that the civet may have served only as an amplification host for SARS-CoV. In a surveillance study for CoV in noncaged animals from the wild areas of the Hong Kong Special Administration Region, we identified a CoV closely related to SARS-CoV (bat-SARS-CoV) from 23 (39%) of 59 anal swabs of wild Chinese horseshoe bats (Rhinolophus sinicus) by using RT-PCR. Sequencing and analysis of three bat-SARS-CoV genomes from samples collected at different dates showed that bat-SARS-CoV is closely related to SARS-CoV from humans and civets. Phylogenetic analysis showed that bat-SARS-CoV formed a distinct cluster with SARS-CoV as group 2b CoV, distantly related to known group 2 CoV. Most differences between the bat-SARS-CoV and SARS-CoV genomes were observed in the spike genes, ORF 3 and ORF 8, which are the regions where most variations also were observed between human and civet SARS-CoV genomes. In addition, the presence of a 29-bp insertion in ORF 8 of bat-SARS-CoV genome, not in most human SARS-CoV genomes, suggests that it has a common ancestor with civet SARS-CoV. Antibody against recombinant bat-SARS-CoV nucleocapsid protein was detected in 84% of Chinese horseshoe bats by using an enzyme immunoassay. Neutralizing antibody to human SARS-CoV also was detected in bats with lower viral loads. Precautions should be exercised in the handling of these animals. PMID:16169905

  4. Novel Inhibitors of Severe Acute Respiratory Syndrome Coronavirus Entry That Act by Three Distinct Mechanisms

    PubMed Central

    Adedeji, Adeyemi O.; Severson, William; Jonsson, Colleen; Singh, Kamalendra; Weiss, Susan R.

    2013-01-01

    Severe acute respiratory syndrome (SARS) is an infectious and highly contagious disease that is caused by SARS coronavirus (SARS-CoV) and for which there are currently no approved treatments. We report the discovery and characterization of small-molecule inhibitors of SARS-CoV replication that block viral entry by three different mechanisms. The compounds were discovered by screening a chemical library of compounds for blocking of entry of HIV-1 pseudotyped with SARS-CoV surface glycoprotein S (SARS-S) but not that of HIV-1 pseudotyped with vesicular stomatitis virus surface glycoprotein G (VSV-G). Studies on their mechanisms of action revealed that the compounds act by three distinct mechanisms: (i) SSAA09E2 {N-[[4-(4-methylpiperazin-1-yl)phenyl]methyl]-1,2-oxazole-5-carboxamide} acts through a novel mechanism of action, by blocking early interactions of SARS-S with the receptor for SARS-CoV, angiotensin converting enzyme 2 (ACE2); (ii) SSAA09E1 {[(Z)-1-thiophen-2-ylethylideneamino]thiourea} acts later, by blocking cathepsin L, a host protease required for processing of SARS-S during viral entry; and (iii) SSAA09E3 [N-(9,10-dioxo-9,10-dihydroanthracen-2-yl)benzamide] also acts later and does not affect interactions of SARS-S with ACE2 or the enzymatic functions of cathepsin L but prevents fusion of the viral membrane with the host cellular membrane. Our work demonstrates that there are at least three independent strategies for blocking SARS-CoV entry, validates these mechanisms of inhibition, and introduces promising leads for the development of SARS therapeutics. PMID:23678171

  5. Screening and identification of severe acute respiratory syndrome-associated coronavirus-specific CTL epitopes.

    PubMed

    Zhou, Minghai; Xu, Dongping; Li, Xiaojuan; Li, Hongtao; Shan, Ming; Tang, Jiaren; Wang, Min; Wang, Fu-Sheng; Zhu, Xiaodong; Tao, Hua; He, Wei; Tien, Po; Gao, George F

    2006-08-15

    Severe acute respiratory syndrome (SARS) is a highly contagious and life-threatening disease that emerged in China in November 2002. A novel SARS-associated coronavirus was identified as its principal etiologic agent; however, the immunopathogenesis of SARS and the role of special CTLs in virus clearance are still largely uncharacterized. In this study, potential HLA-A*0201-restricted spike (S) and nucleocapsid protein-derived peptides were selected from an online database and screened for potential CTL epitopes by in vitro refolding and T2 cell-stabilization assays. The antigenicity of nine peptides which could refold with HLA-A*0201 molecules was assessed with an IFN-gamma ELISPOT assay to determine the capacity to stimulate CTLs from PBMCs of HLA-A2(+) SARS-recovered donors. A novel HLA-A*0201-restricted decameric epitope P15 (S411-420, KLPDDFMGCV) derived from the S protein was identified and found to localize within the angiotensin-converting enzyme 2 receptor-binding region of the S1 domain. P15 could significantly enhance the expression of HLA-A*0201 molecules on the T2 cell surface, stimulate IFN-gamma-producing CTLs from the PBMCs of former SARS patients, and induce specific CTLs from P15-immunized HLA-A2.1 transgenic mice in vivo. Furthermore, significant P15-specific CTLs were induced from HLA-A2.1-transgenic mice immunized by a DNA vaccine encoding the S protein; suggesting that P15 was a naturally processed epitope. Thus, P15 may be a novel SARS-associated coronavirus-specific CTL epitope and a potential target for characterization of virus control mechanisms and evaluation of candidate SARS vaccines. PMID:16887973

  6. Unilateral Partial Nephrectomy with Warm Ischemia Results in Acute Hypoxia Inducible Factor 1-Alpha (HIF-1α) and Toll-Like Receptor 4 (TLR4) Overexpression in a Porcine Model

    PubMed Central

    Zhang, Zhiyong; Haimovich, Beatrice; Kwon, Young Suk; Lu, Tyler; Fyfe-Kirschner, Billie; Olweny, Ephrem Odoy

    2016-01-01

    Purpose Ischemia/reperfusion (I/R) during partial nephrectomy (PN) contributes to acute kidney injury (AKI), which is inaccurately assessed using existent clinical markers of renal function. We evaluated I/R-related changes in expression in hypoxia inducible factor 1α (HIF-1α) and toll-like receptor 4 (TLR4), within kidney tissue and peripheral blood leukocytes (PBL) in a porcine model of PN. Materials and Methods Three adult pigs each underwent unilateral renal hilar cross clamping for 180 min followed by a 15 min reperfusion. The contralateral kidney served as control. Biopsies of clamped kidneys were obtained at baseline (time 0), every 60 min during the hypoxic phase, and post-reperfusion. Control kidneys were biopsied once at 180 min. Peripheral blood was sampled at time 0, every 30 min during the hypoxic phase, and post-reperfusion. HIF-1α and TLR4 expression in kidney tissue and PBL were analyzed by Western blotting. I/R-related histological changes were assessed. Results Expression of HIF-1α in clamped kidneys and PBL was below detection level at baseline, rising to detectable levels after 60 min of hypoxia, and continuing to rise throughout the hypoxic and reperfusion phases. Expression of TLR-4 in clamped kidneys followed a similar trend with initial detection after 30–60 min of hypoxia. Control kidneys exhibited no change in HIF-1α or TLR-4 expression. I/R-related histologic changes were minimal, primarily mild tubular dilatation. Conclusions In a porcine model of PN, HIF-1α and TLR4 exhibited robust, I/R-related increases in expression in kidney tissue and PBL. Further studies investigating these molecules as potential markers of AKI are warranted. PMID:27149666

  7. [Hepatotoxicity in the critically ill patient. The liver under an acute severe insult].

    PubMed

    García de Lorenzo y Mateos, A; Rodríguez Montes, J A

    2008-05-01

    The liver plays an essential role in the metabolism of most of the nutrients since it is a mainly metabolic organ carrying out a series of physiological and metabolic processes related with protein and energy metabolism. The intestinal tract is considered a key element in the development of Multiorgan Dysfunction (MOD) or failure by loosing its barrier function (impaired permeability) against toxins, bio-products and occasionally intraluminal bacteria secondary to hypoxia, one of the main pathophysiogenic mechanisms being the insufficient blood flow to splacnic organs. Liver dysfunction and/or impairment of liver function test are a common event in critically ill patients. They may be due to previous liver cirrhosis or to more immediate causes of liver failure such as sepsis, drugs, liver transplant or any of the multiple etiologies for hepatitis. PMID:18714407

  8. Treatment strategies for acute coronary syndrome with severe mitral regurgitation and their effects on short- and long-term prognosis.

    PubMed

    Lin, Ko-Long; Hsiao, Shih-Hung; Wu, Chieh-Jen; Kang, Pei-Leun; Chiou, Kuan-Rau

    2012-09-15

    Mitral regurgitation (MR) of even mild severity affects the prognosis of patients with acute coronary syndrome (ACS). The present study retrospectively analyzed 1,142 patients with ACS and MR of varying severity. Of the 95 patients with severe MR, 57 (60%) underwent primary percutaneous coronary intervention only and 38 (40%) underwent coronary artery bypass grafting (CABG) and mitral valve replacement (MVR). The severity of MR was significantly associated with the risk of heart failure but not with in-hospital or long-term mortality. In patients with severe MR, in-hospital mortality was no greater in those treated with CABG and MVR than in those treated with percutaneous coronary intervention alone. However, the incidence of long-term hard events (heart failure and all-cause mortality) was lower in those who had received the combined treatment. Multivariate analysis showed that, compared to percutaneous coronary intervention alone, CABG combined with MVR at the acute phase of ACS resulted in a significantly improved prognosis (odds ratio 0.172, 95% confidence interval 0.046 to 0.649, p = 0.009), even after adjusting for age, left ventricular filling pressure, and ejection fraction. In conclusion, the severity of MR in patients with ACS is associated with long-term heart failure events. Even at the acute phase of ACS, CABG combined with MVR results in an acceptable in-hospital mortality rate. The combined strategy also reduced the long-term hard events. PMID:22640972

  9. CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus

    PubMed Central

    Jeffers, Scott A.; Tusell, Sonia M.; Gillim-Ross, Laura; Hemmila, Erin M.; Achenbach, Jenna E.; Babcock, Gregory J.; Thomas, William D.; Thackray, Larissa B.; Young, Mark D.; Mason, Robert J.; Ambrosino, Donna M.; Wentworth, David E.; DeMartini, James C.; Holmes, Kathryn V.

    2004-01-01

    Angiotensin-converting enzyme 2 (ACE2) is a receptor for SARS-CoV, the novel coronavirus that causes severe acute respiratory syndrome [Li, W. Moore, M. J., Vasilieva, N., Sui, J., Wong, S. K., Berne, M. A., Somasundaran, M., Sullivan, J. L., Luzuriaga, K., Greenough, T. C., et al. (2003) Nature 426, 450–454]. We have identified a different human cellular glycoprotein that can serve as an alternative receptor for SARS-CoV. A human lung cDNA library in vesicular stomatitis virus G pseudotyped retrovirus was transduced into Chinese hamster ovary cells, and the cells were sorted for binding of soluble SARS-CoV spike (S) glycoproteins, S590 and S1180. Clones of transduced cells that bound SARS-CoV S glycoprotein were inoculated with SARS-CoV, and increases in subgenomic viral RNA from 1–16 h or more were detected by multiplex RT-PCR in four cloned cell lines. Sequencing of the human lung cDNA inserts showed that each of the cloned cell lines contained cDNA that encoded human CD209L, a C-type lectin (also called L-SIGN). When the cDNA encoding CD209L from clone 2.27 was cloned and transfected into Chinese hamster ovary cells, the cells expressed human CD209L glycoprotein and became susceptible to infection with SARS-CoV. Immunohistochemistry showed that CD209L is expressed in human lung in type II alveolar cells and endothelial cells, both potential targets for SARS-CoV. Several other enveloped viruses including Ebola and Sindbis also use CD209L as a portal of entry, and HIV and hepatitis C virus can bind to CD209L on cell membranes but do not use it to mediate virus entry. Our data suggest that the large S glycoprotein of SARS-CoV may use both ACE2 and CD209L in virus infection and pathogenesis. PMID:15496474

  10. Changes in enzyme activities in tissues of rats exposed to hypoxia (Short Communication)

    PubMed Central

    Cryer, Anthony; Bartley, Walter

    1973-01-01

    Rats were exposed to various degrees of hypoxia and enzyme activities in their tissues were determined. In general, oxidative metabolism was not increased in response to hypoxia, nor was anaerobic metabolism. Physiological and anatomical changes were concluded to be more important than changes in cellular enzyme activities in the overall adaptation to acute hypoxia. PMID:4357712

  11. Accessing Inpatient Rehabilitation after Acute Severe Stroke: Age, Mobility, Prestroke Function and Hospital Unit Are Associated with Discharge to Inpatient Rehabilitation

    ERIC Educational Resources Information Center

    Hakkennes, Sharon; Hill, Keith D.; Brock, Kim; Bernhardt, Julie; Churilov, Leonid

    2012-01-01

    The objective of this study was to identify the variables associated with discharge to inpatient rehabilitation following acute severe stroke and to determine whether hospital unit contributed to access. Five acute hospitals in Victoria, Australia participated in this study. Patients were eligible for inclusion if they had suffered an acute severe…

  12. Functional alterations in macrophages after hypoxia selection.

    PubMed

    Degrossoli, Adriana; Giorgio, Selma

    2007-01-01

    Regions of low oxygen tension are common features of inflamed and infected tissues and provide physiologic selective pressure for the expansion of cells with enhanced hypoxia tolerance. The aim of this study was to investigate whether macrophages resistant to death induced by hypoxia were accompanied by functional alterations. A mouse macrophage cell line (J774 cells) was used to obtain subpopulations of death-resistant macrophages induced by long-term exposure to severe hypoxia (<1% O(2)). The results indicated that exposing J774 macrophages to periods of severe hypoxia results in the selection of cells with phenotypes associated with the modulation of heat-shock protein 70 kDa (HSP70) expression, tumor necrosis factor-alpha (TNF-alpha), and nitric oxide (NO) production and reduced susceptibility to parasite Leishmania infection. Thus, we suggest that hypoxia-selected macrophages may influence the outcome of inflammation and infection. PMID:17202589

  13. Predictors of Severe Acute and Late Toxicities in Patients With Localized Head-and-Neck Cancer Treated With Radiation Therapy

    SciTech Connect

    Meyer, Francois; Fortin, Andre; Wang, Chang Shu; Liu, Geoffrey

    2012-03-15

    Purpose: Radiation therapy (RT) causes acute and late toxicities that affect various organs and functions. In a large cohort of patients treated with RT for localized head and neck cancer (HNC), we prospectively assessed the occurrence of RT-induced acute and late toxicities and identified characteristics that predicted these toxicities. Methods and Materials: We conducted a randomized trial among 540 patients treated with RT for localized HNC to assess whether vitamin E supplementation could improve disease outcomes. Adverse effects of RT were assessed using the Radiation Therapy Oncology Group Acute Radiation Morbidity Criteria during RT and one month after RT, and the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme at six and 12 months after RT. The most severe adverse effect among the organs/tissues was selected as an overall measure of either acute or late toxicity. Grade 3 and 4 toxicities were considered as severe. Stepwise multivariate logistic regression models were used to identify all independent predictors (p < 0.05) of acute or late toxicity and to estimate odds ratios (OR) for severe toxicity with their 95% confidence intervals (CI). Results: Grade 3 or 4 toxicity was observed in 23% and 4% of patients, respectively, for acute and late toxicity. Four independent predictors of severe acute toxicity were identified: sex (female vs. male: OR = 1.72, 95% confidence interval [CI]: 1.06-2.80), Karnofsky Performance Status (OR = 0.67 for a 10-point increment, 95% CI: 0.52-0.88), body mass index (above 25 vs. below: OR = 1.88, 95% CI: 1.22-2.90), TNM stage (Stage II vs. I: OR = 1.91, 95% CI: 1.25-2.92). Two independent predictors were found for severe late toxicity: female sex (OR = 3.96, 95% CI: 1.41-11.08) and weight loss during RT (OR = 1.26 for a 1 kg increment, 95% CI: 1.12-1.41). Conclusions: Knowledge of these predictors easily collected in a clinical setting could help

  14. The impact of physical therapy in patients with severe traumatic brain injury during acute and post-acute rehabilitation according to coma duration

    PubMed Central

    Lendraitienė, Eglė; Petruševičienė, Daiva; Savickas, Raimondas; Žemaitienė, Ieva; Mingaila, Sigitas

    2016-01-01

    [Purpose] The aim of study was to evaluate the impact of physical therapy on the recovery of motor and mental status in patients who sustained a severe traumatic brain injury, according to coma duration in acute and post-acute rehabilitation. [Subjects and Methods] The study population comprised patients with levels of c