Structural Basis for the Inhibition of Gas Hydrates by α-Helical Antifreeze Proteins.

Kinetic hydrate inhibitors (KHIs) are used commercially to inhibit gas hydrate formation and growth in pipelines. However, improvement of these polymers has been constrained by the lack of verified molecular models. Since antifreeze proteins (AFPs) act as KHIs, we have used their solved x-ray crystallographic structures in molecular modeling to explore gas hydrate inhibition. The internal clathrate water network of the fish AFP Maxi, which extends to the protein's outer surface, is remarkably similar to the {100} planes of structure type II (sII) gas hydrate. The crystal structure of this water web has facilitated the construction of in silico models for Maxi and type I AFP binding to sII hydrates. Here, we have substantiated our models with experimental evidence of Maxi binding to the tetrahydrofuran sII model hydrate. Both in silico and experimental evidence support the absorbance-inhibition mechanism proposed for KHI binding to gas hydrates. Based on the Maxi crystal structure we suggest that the inhibitor adsorbs to the gas hydrate lattice through the same anchored clathrate water mechanism used to bind ice. These results will facilitate the rational design of a next generation of effective green KHIs for the petroleum industry to ensure safe and efficient hydrocarbon flow.

Targeting gaseous molecules to protect against cerebral ischaemic injury: mechanisms and prospects.

1. Ischaemic brain injury is a leading cause of death and disability in many countries. However, the pathological mechanisms underlying ischaemic brain injury, including oxidative stress, calcium overload, excitotoxicity and neuronal apoptosis, are perplexing and this makes it difficult to find effective novel drugs for the treatment of the condition. 2. Recently, gaseous molecules such as nitric oxide (NO), carbon monoxide (CO), hydrogen sulphide (H(2)S) and hydrogen (H(2)) have attracted considerable interest because of their physiological and pathophysiological roles in various body systems. Emerging evidence indicates that gaseous molecules are involved in the pathological processes of ischaemic brain damage. 3. In the present review, we summarize evidence regarding the involvement of gaseous molecules in ischaemic brain injury and discuss the therapeutic potential of targeting gaseous molecules. 4. Collectively, the available data suggest that the application of these biological gas molecules and their pharmacological regulators may be a potential therapeutic approach for the treatment of ischaemic brain injury.

Válvula de Boussignac y CPAP frente a diferentes situaciones de temperatura y humedad ambiental / Boussignac CPAP Valve against different situations of temperature and environmental humididty

Introducción. La válvula de Boussigna permite entregar un nivel de presión positiva continua en vía aérea (CPAP) a los enfermos, con la única necesidad de una fuente de gas de alto flujo. Estudiamos si las variaciones en la humedad y temperatura podrían afectar al dispositivo de CPAP. Material y Método. Estudio experimental, realizado en condiciones de laboratorio. Medimos la CPAP conseguida mediante una válvula de Boussignac de Vygon® ante distintas condiciones de humedad y temperatura ambiental. Se utilizaron, además de la citada válvula, una fuente de O2 medicinal con un caudalímetro, un serpentín de cobre para calentar/enfriar el gas, un humidificador Respiflo de Kendall®, y una cubeta de aislamiento térmico. Las mediciones de CPAP se hicieron con un manómetro digital, y las de temperatura y humedad con un termo-higrómetro (previamente calibrados). Tras realizar varias mediciones para un mismo flujo, ante distintas condiciones de humedad y temperatura, se compararon los resultados obtenidos mediante la prueba de la "t" de Student (comparaciones dos a dos) y ANOVA. Se demandó un intervalo de confianza mínimo de 95%. Resultados. Para los diferentes flujos analizados (15, 20 y 25 litros/minuto) se comprueba cómo ante distintas condiciones de temperatura (en rangos de 4-6 ºC, 24-26 ºC y 40-42 ºC) y humedad (2%, 15-20%, 35-40% y 80-85%) se obtienen diferencias estadísticamente significativas en los niveles de CPAP entregados. Conclusión. La temperatura y la humedad a la que se utilicen el oxígeno y el dispositivo de CPAP de Boussignac influyen en los niveles de presión obtenidos, pudiendo llegar a diferencias de presión cercanas al 20% en algunas circunstancias, para un mismo flujo (AU)

Introduction. The Boussignac valve makes it possible to provide a continuous positive airway pressure (CPAP) level to the patients, this only requiring a high flow gas source. We have studied if the variations in gas humidity and temperature could affect the CPAP device. Material and method. Experimental study performed under laboratory conditions. We measured the CPAP obtained with a Boussignac valve (Vygon)®, under different humidity and environmental temperature conditions. In addition to the mentioned valve, a source of medicinal O2, a copper coil to modify the gas temperature, Respiflo humidifier (Kendall)® and a bucket of heat insulation were used. CPAP measurements were made with a digital pressure gauge, and temperature and humidity conditions were measured with a previously calibrated thermus-hygrometer. After several measurements were obtained for a same flow, with different humidity and temperature conditions, the results obtained were compared with the Student's t test (two-sided comparison) and ANOVA. A minimum interval of 95% confidence was required. Resuts: For the different flows analyzed (15, 20 and 25 liters/minute), it was verified that different conditions of temperature (in ranks of 4-6 ºC, 24-26 ºC and 40-42 ºC) and humidity (2%, 15-20%, 35-40% and 80-85%) obtained statistically significant differences in the CPAP levels. Conclusions. The temperature and humidity under which oxygen and Boussignac CPAP device are used influence the CPAP pressure levels, and it was possible to reach differences in pressure close to 20% under some circumstances for a same flow (AU)

Aerobic exercise before diving reduces venous gas bubble formation in humans.

We have previously shown in a rat model that a single bout of high-intensity aerobic exercise 20 h before a simulated dive reduces bubble formation and after the dive protects from lethal decompression sickness. The present study investigated the importance of these findings in man. Twelve healthy male divers were compressed in a hyperbaric chamber to 280 kPa at a rate of 100 kPa min(-1) breathing air and remaining at pressure for 80 min. The ascent rate was 9 m min(-1) with a 7 min stop at 130 kPa. Each diver underwent two randomly assigned simulated dives, with or without preceding exercise. A single interval exercise performed 24h before the dive consisted of treadmill running at 90% of maximum heart rate for 3 min, followed by exercise at 50% of maximum heart rate for 2 min; this was repeated eight times for a total exercise period of 40 min. Venous gas bubbles were monitored with an ultrasonic scanner every 20 min for 80 min after reaching surface pressure. The study demonstrated that a single bout of strenuous exercise 24h before a dive to 18 m of seawater significantly reduced the average number of bubbles in the pulmonary artery from 0.98 to 0.22 bubbles cm(-2)(P= 0.006) compared to dives without preceding exercise. The maximum bubble grade was decreased from 3 to 1.5 (P= 0.002) by pre-dive exercise, thereby increasing safety. This is the first report to indicate that pre-dive exercise may form the basis for a new way of preventing serious decompression sickness.

Hyperbaric oxygen may reduce gas bubbles in decompressed prawns by eliminating gas nuclei.

It is accepted that gas bubbles grow from preexisting gas nuclei in tissue. The possibility of eliminating gas nuclei may be of benefit in preventing decompression sickness. In the present study, we examined the hypothesis that hyperbaric oxygen may replace the resident gas in the nuclei with oxygen and, because of its metabolic role, eliminate the nuclei themselves. After pretreatment with oxygen, prawns were 98% saturated with nitrogen before explosive decompression at 30 m/min. Ten transparent prawns were exposed to four experimental profiles in a crossover design: 1) 10-min compression to 203 kPa with air; 2) 10-min compression with oxygen; 3) 10-min compression with oxygen to 203 kPa followed by 12 min air at 203 kPa; and 4) 10 min in normobaric oxygen followed by compression to 203 kPa with air. Bubbles were measured after explosive decompression. We found that pretreatment with hyperbaric oxygen (profile C) significantly reduces the number of bubbles and bubble volume. We suggest that hyperbaric oxygen eliminates bubble nuclei in the prawn.

Superoxide released from neutrophils causes a reduction in nitric oxide gas.

Exhaled nitric oxide (NO) is increased in some inflammatory airway disorders but not in others such as cystic fibrosis and acute respiratory distress syndrome. NO can combine with superoxide (O-2) to form peroxynitrite, which can decompose into nitrate. Activated polymorphonuclear neutrophils (PMNs) releasing O-2 could account for a reduction in exhaled NO in disorders such as cystic fibrosis. To test this hypothesis in vitro, we stimulated confluent cultures of LA-4 cells, a murine lung epithelial cell line, to produce NO. Subsequently, human PMNs stimulated to produce O-2 were added to the LA-4 cells. A gradual increase in NO in the headspace above the cultures was observed and was markedly reduced by the addition of PMNs. An increase in nitrate in the culture supernatant fluids was measured, but no increase in nitrite was detected. Superoxide dismutase attenuated the PMN effect, and xanthine/xanthine oxidase reproduced the effect. No changes in epithelial cell inducible NO synthase protein or mRNA were observed. These data demonstrate that O-2 released from PMNs can decrease NO by conversion to nitrate and suggest a potential mechanism for modulation of NO levels in vivo.