Gene/Protein Disease Symptom Drug Enzyme Compound
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 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of two pharmacologically distinct histamine H2 receptor antagonists were studied in combination with ibuprofen (I) and diphenhydramine (D) in a porcine model of septic ARDS. Cimetidine (C) is reported as having direct oxygen radical scavenging abilities and is an inhibitor of cytochrome P-450, whereas ranitidine (R) acts solely by H2 receptor blockade. Four groups were studied: Group Ps (n = 8) received a continuous infusion of live Pseudomonas aeruginosa 5 x 10(8) CFU/ml at 0.3 ml/20kg/min, Group C (n = 6) received a control saline infusion, and the treatment groups received I (12.5 mg/kg) and D (10 mg/kg) in combination with either C (150 mg, CID, n = 6) or R (25 mg, RID, n = 5) given at 20 and 120 minutes after the onset of Ps. Pulmonary (PAP) and systemic (SAP) arterial pressures, cardiac index (CI), PaO2, thermal cardiogreen extravascular lung water (EVLW) and scintigraphically determined pulmonary albumin flux (slope index, SI) were measured. Ps infusion produced significant (p less than 0.05) cardiovascular collapse, hypoxemia and increased EVLW and SI. Both CID and RID temporarily reversed pulmonary arterial hypertension and maintained PaO2, EVLW, SAP and CI at control levels throughout the study, and significantly improved SI at 180 min. These results suggest that cimetidine and ranitidine act in this combination therapy primarily as H2 receptor antagonists.
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PMID:Ranitidine compared to cimetidine in multiagent pharmacological treatment of porcine Pseudomonas ARDS. 231 Dec 2

The ease with which fluid passes across the synovial lining (i.e., the lining's hydraulic conductance) is enhanced when intraarticular fluid pressure (IAP) is raised acutely to pathological levels in rabbit knees. A structural basis for this pathophysiological change was sought by morphometry of synovial sections from rabbit knees fixed in situ at less than or equal to 5 cm H2O and 25 cm H2O IAP. Light and electron microscopy showed that the main structural changes induced in areolar synovium by raising IAP to 25 cm H2O were (1) a reduction in synovial thickness to 56% control value; (2) an increase in the area of interstitium exposed at the synovial surface (3) an increased proximity of the synovial capillaries to the joint lumen, the mean distance of capillaries from the surface falling from 8.9 +/- 0.5 microns (n = 391) to 3.3 +/- 0.3 microns (n = 92: p less than 0.001). The capillary profiles showed slight compression under 25 cm H2O IAP, but no collapse. The ratio of interstitial area to thickness is the geometric factor governing hydraulic conductance. The maximum change in interstitial area/thickness was 6.8 times for the blood-joint barrier. A change of this magnitude accounts partly (but not fully) for the experimentally observed conductance changes; and it highlights the importance of capillary depth as a factor governing exchange in joints.
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PMID:Pressure induced deformation of the interstitial route across synovium and its relation to hydraulic conductance. 233 56

The epimerization of moxalactam (LMOX) in frozen urine and plasma samples was studied during long-term storage. The R/S ratio at equilibrium [(R/S)eq] at -10 degrees C was similar in urine and in rat and human plasma ultrafiltrate but differed from that in water. The (R/S)eq values in human plasma and its ultrafiltrate differed slightly, while they were the same in rat plasma and in its ultrafiltrate. The difference for the human plasma and ultrafiltrate may result from differences in plasma protein binding between R- and S-epimers in the liquid region of the frozen plasma. The change of R/S ratio in frozen human plasma continued below the collapse temperature of LMOX aqueous solution, where the liquid region appeared still to exist as determined by NMR measurement. Consequently, the biological LMOX samples should be preserved at or below -70 degrees C to prevent changes in the R/S ratio.
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PMID:Epimerization kinetics of moxalactam in frozen urine and plasma samples. 236 9

Two enantiomeric analogues of farnesyl pyrophosphate (1) were tested as inhibitors and anomalous substrates of trichodiene synthase, which catalyzes the cyclization of trans,trans-farnesyl pyrophosphate (1) to the sesquiterpene hydrocarbon trichodiene (2). The reaction has been shown to involve preliminary isomerization of 1 to the tertiary allylic isomer nerolidyl pyrophosphate (3) which is cyclized without detectable release of the intermediate from the active site of the cyclase. Both (7S)-trans-6,7-dihydrofarnesyl pyrophosphate (7a) and (7R)-trans-6,7-dihydrofarnesyl pyrophosphate (7b), prepared from (3R)- and (3S)- citronellol (9a and 9b), respectively, proved to be modest competitive inhibitors of trichodiene synthase. The values of Ki(7a), 395 nM, and Ki(7b), 220 nM, were 10-15 times the observed Km for 1 and half the Ki of inorganic pyrophosphate alone. Incubation of either 7a or 7b with trichodiene synthase resulted in formation of a mixture of products which by radio/gas-liquid chromatographic and GC/selected ion mass spectrometric analysis was shown to be composed of 80-85% isomeric trienes 19-21 and 15-20% allylic alcohols 12 and 18. Examination of the water-soluble products resulting from incubation of 7a also revealed the generation of 24% of the isomeric cis-6,7-dihydrofarnesyl pyrophosphate (26). The combined rate of formation of anomalous alcoholic and olefinic products was 10% the Vmax determined for the conversion of 1 to 2. The results can be explained by initial enzyme-catalyzed isomerization of dihydrofarnesyl pyrophosphate (7) to the corresponding tertiary allylic isomer dihydronerolidyl pyrophosphate (8). Since the latter intermediate is unable to cyclize due to the absence of the 6,7-double bond, ionization of 8 and quenching of the resulting ion pair by deprotonation, capture of water, or collapse to the isomeric primary pyrophosphate esters will generate the observed spectrum of anomalous products.
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PMID:Studies of the cryptic allylic pyrophosphate isomerase activity of trichodiene synthase using the anomalous substrate 6,7-dihydrofarnesyl pyrophosphate. 238 80

We studied the first 24-hour lung and systemic physiologic response to a moderate smoke inhalation injury. In addition, we monitored oxidant-induced lipid peroxidation (LP), using malondialdehyde and conjugated dienes. Sixteen adult sheep with lung and soft tissue lymph fistulas were given 20 breaths of smoke while under anesthesia. Eight sheep were given a tidal volume of 5 ml/kg smoke, confining the inflammatory injury to airways only. Eight sheep were given 10 ml/kg smoke after which focal alveolar collapse and a carboxyhemoglobin level of 28% +/- 5% were noted in addition to airways injury. No significant lung or systemic physiologic changes were noted in the 5 ml/kg smoke exposure. However, plasma levels of malondialdehyde increased significantly, indicating that LP had occurred. With the 10 ml/kg smoke exposure, a 50% early decrease in oxygen consumption was noted. At 12 hours, oxygen consumption was then significantly increased by 30% over baseline. Fluid requirements to maintain filling pressures were also significantly increased, comparable to that seen after a 20% total body surface burn. A change in soft tissue permeability was noted with a twofold increase in systemic lymph, which could in part explain the fluid requirements. Lung lymph flow increased by only twofold, and lung water was not increased, whereas arterial partial oxygen pressure decreased from a baseline of 95 +/- 4 mm Hg to 60 +/- 5 mm Hg. Systemic LP was evident when both plasma malondialdehyde and conjugated dienes increased significantly. Liver tissue malondialdehyde at postmortem examination was double the normal level. However, lung parenchymal malondialdehyde was not increased.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Moderate smoke inhalation produces decreased oxygen delivery, increased oxygen demands, and systemic but not lung parenchymal lipid peroxidation. 239 98

The highly hydrated capsule of E. coli strains is composed of a large number of polysaccharide fibers of which the thinnest measure about 2 nm in width. The fibers may span the entire distance from the outer membrane to the outer rim of the capsule and show a propensity to associate with each other to form thicker filaments. Presence of thick filaments may also indicate a partial collapse of the capsular organization due to removal of water. The in vivo capsule represents a relatively open structure with the negatively charged polysaccharide fibers permitting the binding of large quantities of water and ions, and providing intracellular space for diffusing molecules to access the envelope membranes even in conditions of high cell density. Negative charge and steric hindrance of the polysaccharide strands protect the cells against attack by a large variety of harmful macromolecules and against infection by most bacteriophages. Two types of procedure have been most successful in maintaining the size and overall structure of the capsule: (a) the interaction of cationic molecules with the in vivo capsule, and (b) the use of antibody to stabilize capsules for subsequent dehydration and plastic embedding. A further type of potentially useful procedure, cryofixation and cryosubstitution, has shown interesting results in a number of cases. These techniques are expected to play a significant role in structural studies in the near future. The sites of export of capsular antigen have been described in earlier conventional electron microscopic studies. Data obtained from the recent technique of "on-section" labeling support the model that both the capsular antigen and the O antigen are assembled at junctions of the inner and outer membrane. It is anticipated that one will be able to discern in greater ultrastructural detail the membranes at which the antigen is translocated. Novel membrane fixation and isolation techniques will have to be established and employed in a combination of sensitive microscopic techniques and immuno- and enzyme localization methods. These developments will make it possible to explore questions pertaining to the maintenance and structural organization of microbial capsules and the functional interaction of polysaccharides with natural surfaces, man-made substances and drugs.
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PMID:Visualization of the bacterial polysaccharide capsule. 240 87

The upper airway (UAW) is intrinsically unstable and susceptible to collapse when the negative inspiratory intraluminal pressure exceeds the stabilizing forces which prevent obstruction. In the present study we evaluated mechanisms by which UAW patency is maintained in the presence of increased inspiratory flows when respiration is stimulated. In seven anesthetized dogs breathing spontaneously through a low tracheostomy, the UAW was isolated by a second tracheostomy directed rostrally. UAW pressure-flow relationship and stability against collapse were evaluated during steady flow in the inspiratory direction while the animals were breathing 100% O2 or a hypercapnic gas mixture. The pressure-flow curves of the isolated UAW demonstrated the characteristic pattern of collapsible tubes. Steady state hypercapnia resulted in lower UAW resistance during both inspiration and expiration. UAW resistance decreased linearly as PCO2 and ventilation increased over the course of CO2 rebreathing. In addition, during hypercapnia the critical negative intraluminal pressure required to induce UAW collapse and obstruction increased from -4.3 +/- 0.9 to -8.5 +/- 1.5 SE cm H2O (p less than 0.01), indicating increased stability of the UAW. Since hypercapnia is known to stimulate UAW muscles, our findings suggest that increased UAW muscle activity improves UAW patency both by decreasing their resistance to airflow, and by increasing UAW walls rigidity and stability against collapse.
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PMID:Effect of hypercapnia on upper airway resistance and collapsibility in anesthetized dogs. 249 2

Giant emphysematous bullae are believed to produce symptoms of pulmonary compression and collapse by containing gas under pressure that has been generated through valvular feeding airways. To examine this hypothesis, we have measured oxygen and carbon dioxide tensions (PO2, PCO2) in four patients and pressure within the bullae in three patients immediately before surgery. During spontaneous tidal respiration PO2 in the bulla was higher than arterial PO2 but did not rise as fast during the breathing of oxygen. The intra-bulla pressure during inspiration was negative (-5.5 to -19 cm H2O) and similar to pleural pressure in phase and degree. During intermittent positive pressure ventilation in two patients airway pressures were transmitted to the bulla with the development of a positive end expiratory pressure within the bulla. Histological examination of the walls of the bullae in the four patients and adjacent lung tissue in an additional patient failed to identify any valvular mechanism. The available information suggests that bullae develop after retraction and collapse of surrounding lung away from a region of weakness.
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PMID:Origin and behaviour of emphysematous bullae. 250

Compression isotherms of astaxanthin (AX; 3,3'-dihydroxy-4,4'-dioxo-beta-carotene) monolayers, recorded at the air/water interface show, on the one hand, the collapse pressure to depend on the subphase pH, indicating the ionisation of AX at high pH values, and on the other hand, the subphase Co2+ ions to have a condensing effect upon the monolayer and to entail the increase of its collapse pressure. The latter effects are assigned to surface complex formation. The interfacial tension at the benzene/water interface (the benzene phase containing AX, the water phase Co2+ ions) exhibit a maximum at a molar ratio AX: Co of about 3.6, pleading for the formation of relatively stable Co(AX)4 type interfacial complex. Geometric model and ligand field considerations show besides the dative type sigma-bond formation, the possibility of both dative and retrodative type pi-bond formation between Co2+ and the AX ligands. Under the working conditions used, the formation of a neutral non-electrolyte type complex of the composition [Co(LH)2L2] is postulated, where LH stands for the neutral AX molecule, L- for its anion.
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PMID:Surface complexes of xanthophyll films with transition metal ions. 251 60

Nephrocalcin is a urinary glycopeptide that may be a physiological inhibitor of nephrolithiasis. Monomeric nephrocalcin purified from ethylenediaminetetracetic acid-treated urine is 14,000 daltons. Compositional analyses indicate that nephrocalcin is 10 per cent carbohydrate by weight and that 25 per cent of the amino acid residues are acidic (glutamic acid, aspartic acid and gamma-carboxyglutamic acid). Nephrocalcin binds reversibly to calcium oxalate crystals with a dissociation constant of about 0.5 microM. The high collapse pressure of nephrocalcin, 41.5 dynes per cm., measured for a monolayer at the air-water interface, suggests a highly organized structure in which hydrophilic and hydrophobic regions occupy separate regions on the surface of the inhibitor. Nephrocalcin contains the unusual amino acid, gamma-carboxyglutamic acid. Nephrocalcin isolated from urine of stone formers and from kidney stones does not contain gamma-carboxyglutamic acid and it has altered surface properties compared to normal nephrocalcin. The presence of the gamma-carboxyglutamic acid modification and the ability to form stable films with high collapse pressures may be important factors enabling nephrocalcin to prevent stone formation in vivo. The blood of cold water fishes contains antifreeze glycopeptides and/or peptides to prevent it from freezing. The structure of one such antifreeze peptide and its interactions with the crystal lattice of hexagonal ice are discussed as a model for how nephrocalcin might interact with calcium oxalate crystals and arrest their growth in urine.
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PMID:Protein inhibitors of crystal growth. 264 34


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