Effects of ibuprofen on airway vascular response to cotton smoke injury

We studied the effects of ibuprofen on bronchial blood flow and myocardial function after inhalation injury. Sheep (n = 12) were chronically instrumented with cardiovascular and pulmonary catheters. After 5 days of recovery period, baseline data were collected and the sheep were divided into two groups. Group S (n = 6) were insufflated with 48 breaths of cotton smoke; while group I (n = 6) were pretreated with ibuprofen (12mg/kg bolus followed by 3 mg/kg/h continuous infusion for 24 h) and challenged with the same dose of smoke. All the animals were studied for 24h. Bronchial blood flow increased significantly in both groups throughout the experimental period; while stroke volume as well as right and left ventricular stroke work indices of both groups were significantly decreased (group I worse than group S) in the second half of the experimental period. These data suggest that vasodilatory prostaglandins do not play a major role in the bronchial vascular response to smoke inhalation injury and myocardial depression seen post injury is worse in animals treated with ibuprofen.     

Protein thermostability above 100 degreesC: a key role for ionic interactions

The discovery of hyperthermophilic microorganisms and the analysis of hyperthermostable enzymes has established the fact that multisubunit enzymes can survive for prolonged periods at temperatures above 100 degreesC. We have carried out homology-based modeling and direct structure comparison on the hexameric glutamate dehydrogenases from the hyperthermophiles Pyrococcus furiosus and Thermococcus litoralis whose optimal growth temperatures are 100 degreesC and 88 degreesC, respectively, to determine key stabilizing features. These enzymes, which are 87% homologous, differ 16-fold in thermal stability at 104 degreesC. We observed that an intersubunit ion-pair network was substantially reduced in the less stable enzyme from T. litoralis, and two residues were then altered to restore these interactions. The single mutations both had adverse effects on the thermostability of the protein. However, with both mutations in place, we observed a fourfold improvement of stability at 104 degreesC over the wild-type enzyme. The catalytic properties of the enzymes were unaffected by the mutations. These results suggest that extensive ion-pair networks may provide a general strategy for manipulating enzyme thermostability of multisubunit enzymes. However, this study emphasizes the importance of the exact local environment of a residue in determining its effects on stability.     

Familial transmission of a serious disease--producing group A streptococcus clone: case reports and review

Invasive group A streptococcus (GAS) infections are emerging diseases; however, person-to-person transmission of invasive GAS producing life-threatening infection has been observed rarely. We report a small intrafamilial cluster of life-threatening GAS infections. A previously healthy 47-year-old father developed necrotizing fasciitis of the neck. Two days later, his 16-year-old daughter developed streptococcal angina, pneumonia, and pleural empyema. Both patients had signs of streptococcal toxic shock syndrome. Pulsed field gel electrophoresis revealed that the M6 strains of GAS isolated from the father and daughter had identical patterns. Cases of person-to-person transmission of invasive GAS infection reported in the literature are also reviewed.     

Dynamics of cyanide binding to ferrous Scapharca inaequivalvis homodimeric hemoglobin

Flash photolysis experiments have been carried out for the first time on a hemoglobin ferrous cyanide adduct with an 8 ns laser pulse. A 95% nonexponential rebinding process occurs within 2 micros after full photolysis in ferrous cyanide dimeric Scapharca inaequivalvis hemoglobin (HbI), indicating that once photolyzed the cyanide anion is not able to escape from the protein matrix and rebinds to the heme iron. The resonance Raman spectrum of the 10 ns photoproduct is identical to that of the fully relaxed deoxy derivative, indicating that in the ferrous cyanide HbI adduct protein relaxation occurs within 10 ns after photolysis. This behavior is at variance with that of the carbonmonoxy HbI derivative in which very little geminate rebinding is observed and the photoproduct relaxes with a lifetime of 1 micros. The fast relaxation of the cyanide HbI photoproduct can be accounted for by the small perturbation of the heme structure induced by cyanide binding to ferrous HbI. This is consistent with a deoxy-like conformation of the HbI ferrous cyanide adduct and implies that the pathway for relaxation involves only minor local rearrangements of the heme moiety. Photolysis experiments carried out on ferrous cyanide horse myoglobin, which can be saturated only partially, show a qualitatively similar behavior in ligand rebinding, indicating that the geminate process of the cyanide anion is a general phenomenon in hemoproteins.     

Anomalous behavior of unplasticized PVC compounds in capillary flow

Capillary rheometry was performed over a temperature range of 170°–200°C and a shear-rate range of 3–3000 sec^?1 on an unplasticized poly(vinyl chloride) compound. The data were corrected for the effect of pressure on viscosity, for pressure loss in the barrel and at the capillary entrance, and for the non-Newtonian velocity profile. The pressure coefficient of viscosity was found to be in the same order of magnitude as those previously found with linear polyethylene and butadieneacrylonitrile copolymers. The pressure–shear-rate superposition of the flow curves is valid at least approximately, although the temperature–shear-rate superposition is inapplicable. The shape of flow curves at 180°, 190°, and 200°C are concave downward when they are expressed as log-shear-stress-log-shear-rate. Similar plots at 170° and 175°C, however, are very different; shear stress is independent of shear rate at low shear rates, increases somewhat and becomes independent of shear rate again at high shear rates. There is no detectable temperature dependence of flow behavior at 170° and 175°C. Irregularly shaped extrudates were obtained at higher shear rates. At constant shear rate the irregularity increased with the length of the capillary. The effect of thermal-mechanical history on the particulate and crystalline structure is discussed with possible influence on the reproducibility of the rheological data.     

Spatio-temporal analysis of trap catches of Tribolium confusum du Val in a semolina-mill, with a comparison of female and male distributions

By using food-bait traps, we evaluated the presence and the spatio-temporal distribution of insect pests in an industrial semolina-mill, with particular attention to Tribolium confusum du Val in which the spatio-temporal dynamics of females and males were also studied separately. A total of 1401 insect specimens was captured in the traps, belonging to 14 taxa, mainly Coleoptera. The most abundant species were T. confusum (with 1002 adults), followed by Typhaea stercorea (L.) (with 158 adults) and T. castaneum (Herbst) (with 110 adults). Of particular interest was the presence in the food-bait traps of T. confusum and T. castaneum adults in a mixed population with equal numbers of males and females. Furthermore, analysis of the spatio-temporal dynamics suggested that the distribution of the two sexes in T. confusum was almost the same during the entire sampling period. The findings of our study can usefully be applied to the management of Tribolium infestations, but further and more detailed studies are needed to better understand the ecology and behaviour of the species in association with searching for food and production of aggregation pheromones.     

Isolation of Ambient Particles of Known Critical Supersaturation: The Differential Activation Separator (DAS)

A field-deployable instrument has been developed that isolates from an ambient aerosol those particles that have critical supersaturations, S_c, within a narrow, user-specified, range. This Differential Activation Separator (DAS) consists of two continuous flow diffusion chambers housed within a single enclosure. Particles are introduced into the upstream chamber referred to as the CCN remover (CCNR) near the centerline between a warm, water-soaked, plate and a cool, continuously circulated, water bath. Those particles that activate at the resulting peak supersaturation, S_p, grow quickly and fall into the water bath. The remaining aerosol enters the second chamber referred to as the CCN separator (CCNS), which differs from the CCNR primarily in the use of a salt solution in the lower bath. The imposed temperature differential establishes an S_p slightly higher than that maintained in the upstream chamber, while the presence of a salt solution at the lower boundary results in a subsaturated region in roughly the lower half of the chamber. Those particles having (S_p)_CCNR < S _c < (S_p)_CCNS activate in this chamber and begin to fall due to gravitational settling. Before reaching the lower bath, the droplets evaporate in the subsaturated environment and continue to travel towards the chamber exit. The previously activated particles in the lower half of the chamber and the unactivated particles in the upper half are extracted in separate flows that are subsequently dried. Calibration of the DAS was achieved by measuring the size distribution of separated particles when a polydisperse ammonium sulfate aerosol was introduced.     

ATR-FTIR Study of the Decomposition of Acetic Anhydride on Fosfotungstic Wells–Dawson Heteropoly Acid Using Concentration-Modulation Excitation Spectroscopy

The decomposition of acetic anhydride in liquid phase on a fosfotungstic Wells–Dawson heteropoly acid (HPA) was investigated by in situ ATR-FTIR spectroscopy. Transient and concentration-modulation excitation spectroscopy (MES) experiments in combination with phase-sensitive detection (PSD) were used to monitor the solid–liquid interface. The MES method is based on the periodic variation of a parameter of the reaction media such as, the reactant concentration. That periodic alteration causes varying infrared signals of the surface adsorbed species that are subsequently demodulated with the PSD methodology. Thus, the separation of the static signals from the changing ones is achieved, and species with different response can be observed in the spectra. Using MES-PSD coupled with ATR-FTIR, acetic anhydride was observed to decompose to acetic acid, acetate and acyl [CH₃C(O)⁺] species, involving Brønsted acid sites of the HPA catalyst. The CH₃C(O)⁺ is a very unstable intermediate species and it is the key intermediate in the Friedel–Crafts acylation reactions. Moreover, the acetate groups are spectator species since remain strongly adsorbed on the catalyst surface and do not further react.     

Mechanism of cytotoxicity and cellular uptake of lipophilic inert dinuclear polypyridylruthenium(II) complexes

The accumulation, uptake mechanism, cytotoxicity, cellular localisation of—and mode of cell death induced by—dinuclear ruthenium(II) complexes ΔΔ/ΛΛ‐[{Ru(phen)₂}₂{μ‐bb_n}]⁴⁺ (Rubb_n), where phen is 1,10‐phenanthroline, bb_n is bis[4(4′‐methyl‐2,2′‐bipyridyl)]‐1,n‐alkane (n=2, 5, 7, 10, 12 or 16), and the corresponding mononuclear complexes containing the bb_n ligands, were studied in L1210 murine leukaemia cells. Cytotoxicity increased with linker chain length, and the ΔΔ‐Rubb₁₆ complex displayed the highest cytotoxicity of the series, with an IC₅₀ value of 5 μM , similar to that of carboplatin in the L1210 murine leukaemia cell line. Confocal microscopy and flow cytometry studies indicated that the complexes accumulate in the mitochondria of L1210 cells, with the magnitude of cellular uptake and accumulation increasing with linking chain length in the bb_n bridge of the metal complex. ΔΔ‐Rubb₁₆ entered the L1210 cells by passive diffusion (with a minor contribution from protein‐mediated active transport), inducing cell death via apoptosis. Additionally, metal‐complex uptake in leukaemia cells was approximately 16‐times that observed in healthy B cells highlighting that the bb_n series of complexes may have potential as selective anticancer drugs.