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The concentrations of cationic local anesthetics present in effluents from subsegmental bronchoscopic lavage were determined. Subsequently, the effect of these agents on lavaged human AM was evaluated in vitro. The results indicate that concentrations of LDC that may alter human AM function are present in effluents during routine subsegmental bronchopulmonary lavage. LDC and TRC in a dose-dependent fashion rapidly inhibited oxygen consumption and superoxide anion (O-2.) release by unstimulated human AM or AM stimulated by bacteria or the membrane-active chemical PMA. Concentrations of 2 mM TRC or 16 mM LDC reduced O2 consumption and O-2. release by unstimulated AM by more than 70% and blocked the usual spurt in O2 uptake and O-2. release observed for stimulated AM. This inhibition was not due to cytotoxicity, since washing n a balanced salt solution restored the metabolic function of treated AM. TRC or LDC also had effects on the morphology of washed human AM, causing rounding of the cell surface (scanning electron microscopy). In summary, the findings show that anesthetic agents routinely present in lavage effluents have the capacity to alter the function and structure of human AM. Although the effect must be considered in the design and interpretation of studies using AM obtained by bronchopulmonary lavage, the cationic anesthetics may also prove to be valuable agents for evaluating cell membrane-related events of human AM.
J Lab Clin Med 1979 May
PMID:Influence of cationic local anesthetics on the metabolism and ultrastructure of human alveolar macrophages. 21 25

Cytochrome P-450cam, the bacterial hemeprotein which catalyzes the 5-exo-hydroxylation of d-camphor, requires two electrons to activate molecular oxygen for this monooxygenase reaction. These two electrons are transferred to cytochrome P-450cam in two one-electron steps by the physiological reductant, putidaredoxin. The present study of the kinetics of reduction of cytochrome P-450cam by reduced putidaredoxin has shown that the reaction obeys first order kinetics with a rate constant of 33 s-1 at 25 degrees C with respect to: 1) the appearance of the carbon monoxide complex of Fe(II) cytochrome P-450cam; 2) the disappearance of the 645 nm absorbance band of high-spin Fe(III) cytochrome P-450cam; and 3) the disappearance of the g = 1.94 EPR signal of reduced putidaredoxin. This data was interpreted as indicative of the rapid formation of a bimolecular complex between reduced putidaredoxin Fe(III) cytochrome P-450cam. The existence of the complex was first shown indirectly by kinetic analysis and secondly directly by electron paramagnetic resonance spectroscopic analysis of samples which were freeze-quenched approximately 16 ms after mixing. The direct evidence for complex formation was the loss of the EPR signal of Fe(III) cytochrome P-450cam upon formation of the complex while the EPR signal of reduced putidaredoxin decays with the same kinetics as the appearance of Fe(II) cytochrome P-450. The mechanism of the loss of the EPR signal of cytochrome P-450 upon formation of the complex is not apparent at this time but may involve a conformational change of cytochrome P-450cam following complex formation.
Acta Biol Med Ger 1979
PMID:Cytochrome P-450cam and putidaredoxin interaction during electron transfer. 22 72

After reduction by dithiothreitol and removal of the reductant by molecular sieve chromatography, the four interchain disulfide bonds of the human IgGlk protein Fro reoxidize in the presence of oxygen and trace metal ions. The six molecular components of the reoxidation--L (light chain), H (heavy chain), HL, H2, H2L, H2L2--are quantitatively determined from polyacrylamide gels containing sodium dodecyl sulfate and the time-dependent sulfhydryl titer is measured with 5,5'-dithiobis-(2-nitrobenzoic acid). The rates of H2L2 covalent assembly depend on pH in an unexpected way: If the reduced protein is chromatographed at pH 3.2 and then adjusted to pH 7.5 (25 degrees, ionic strength equals 0.14), H2L2 formation proceeds rapidly, with half-times ranging between 20 and 40 min. In contrast, if chromatography is carried out at pH 5.5 before adjusting to the same final conditions, the half-times for H2L2 formation are considerably longer (120-180 min). The half-times in the former case approach the somewhat faster rates of H2L2 assembly observed in pulse-chase experiments with various types of mouse, IgG-producing cells [Baumal, et al. (1971) J. Exp. Med. 134, 1316-1334]. To facilitate comparison of experiments and models, we plot the concentrations of the six components against the corresponding number of sulfhydryl equivalents per mole of Fro. The respective plots for the pH 3.2 leads to 7.5 and 5.5 leads to 7.5 experiments are very similar despite the rate differences. Moreover, these plots differ significantly from the calculated plot for a hypothetical random reoxidation in which the intrinsic probability for formation of each correct HL and H2 disulfide bond is assumed equal and independent. It is concluded that the in vitro reoxidation of Fro (i) is other than random; (ii) involved a pathway of pathways with HL, H2, and H2L precursors; and (iii) involves at least some kinetic cooperativity in bond formation, since no model bases solely on independent bond formation adequately accounts for the results. The models were used also to examine the cellular assembly pathways of mouse IgG proteins.
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PMID:A kinetic study in vitro of the reoxidation of interchain disulfide bonds in a human immunoglobulin IgGLk. Correlation between sulfhydryl disappearance and intermediates in covalent assembly of H2L2. 23 27

Direct measurements of the factors determining blood oxygen transport in 10 patients with chronic hypoxic respiratory failure led to the conclusion that wide differences in the position of their oxygen binding curves, due to spontaneous differences in red-cell 2, 3-diphosphoglycerate, had little effect on oxygen delivery to the tissues, as assessed by the mixed venous oxygen tension when they were breathing air. This result arises from the shape of the oxygen binding curve. A drug which could shift the curve to the right would help tissue oxygenation in cardiogenic and other forms of shock, when a low cardiac output can not be improved though arterial blood can be well oxygenated.
Br Med J 1975 Mar 15
PMID:Changes in haemoglobin binding curve and oxygen transport in chronic hypoxic lung disease. 23 67

Ten patients underwent 4 study hemodialyses, one with standard dialysis conditions, one with an isophosphate dialysate, one with simultaneous ammonium chloride loading, and other, after pretreatment, with sodium bicarbonate. Measurement of hemoglobin oxygen affinity (P-50), erythrocyte 2,3-DPG, blood-gasses, and serum chemistries revealed biochemically effective hemodialyses and slight changes in oxygen transport parameters. The P-50 (in vivo) values decreased slightly but significantly (p greater than 0.05) with dialysis. When corrected to pH 7.4, eliminating the Bohr effect, P-50 increased (p greater than 0.05). With unmodified dialysis elevated values of 2,3-DPG (in comparison to normal) decreased, a change that did not correlate with delta-p-50, delta-serum phosphate, or delta-serum creatinine. With standard and isophosphate dialyses Po-2 decreased significantly. The decrease correlated with delta-hydrogen ion concentration and did not occur with dialyses designed to maintain pH constant. Thus, hemodialysis influences many factors that affect oxygen transport in different and counterbalancing directions. These changes are not totally explained by alterations in 2,3-DPG, pH or serum phosphate. Maintenance of acidosis or hyperphosphatemia during dialysis is not recommended.
J Lab Clin Med 1975 Jun
PMID:Effect of hemodialysis on factors influencing oxygen transport. 23 54

Tissue hypoxia as a result of a wide variety of clinical situations had frequently been implicated as a cause of systemic acidosis due to the accumulation of lactic acid. Four patients suffering from smoke inhalation had lactic acidosis in association with carboxyhemoglobinemia. There was no evidence of decreased tissue perfusion, hypotension, arterial hypoxemia, or anemia. The following were tested in all patients: arterial pH (7.25 to 7.40), Pco-2 (19 to 27 mm Hg), Po (63 to 116 mm Hg), HCO-2- (11 to 19 meq/litre), carboxyhemoglobin (13% to 37%), and lactic acid (5.1 to 9.3 meq/litre). After therapy with oxygen and intravenous corticosteroids, there was prompt return of lactic acid levels, carboxyhemoglobin values, and arterial pH to normal. It is concluded that the cause of lactic acidosis in the presence of carboxyhemoglobinemia during smoke inhalation is tissue hypoxia. This tissue hypoxia is due to the reduction of the oxygen-carrying capacity of the blood and the concomitant shift of the oxyhemoglobin dissociation curve to the left, both known to result from carboxyhemoglobinemia.
Ann Intern Med 1975 Jun
PMID:Lactic acidosis from carboxyhemoglobinemia after smoke inhalation. 23 51

Cardiopulmonary variables were studied in rabbits breathing room air following 24-36 h of 100 percent 0-2 exposure. Initially, arterial pH and P-co-2 remained within normal limits while arterial P-0-2 decreased significantly. Cardiac output and oxygen consumption increased significantly. Static lung compliance was decreased, and histologic examination showed pulmonary hemorrhage, atelectasis, and adema. Myocardial function under these conditions was restored, and the myocardium was able to produce a compensatory increase in cardiac output. Therefore, changes in myocardial function, as related to oxygen toxicity, are reversable phenomena.
Aviat Space Environ Med 1975 Apr
PMID:Cardiopulmonary changes following 24-36 hours of hyperoxia. 23

1. The acid-base state of arterial blood and cerebrospinal fluid, and the ventilatory response to CO2, were measured in twelve patients with liver disease. The CO2 response was also measured in eight goats before and after the experimental production of liver failure. Arterial PCO2 and pH, cerebral blood flow and the cerebral metabolic rate for oxygen were also measured in four of the goats while they breathed air and various CO2-enriched gas mixtures. 2. Liver failure was accompanied by a respiratory alkalosis in both the patients and in the goats. Decreased PCO2 and increased pH occurred in the cerebrospinal fluid and in the arterial blood of the patients. 3. The slope of the ventilatory response to CO2 was reduced when liver failure was severe, in patients and goats alike. In addition there was a reduction in the extrapolated PCO2 at zero ventilation, even when liver failure was mild. 4. Cerebral blood flow and metabolic rate were consistently reduced in the goats during liver failure. There was also less cerebral vasodilatation and a greater reduction in cerebral metabolism during experimental hypercapnia when these animals were in liver failure. 5. The decreases in the ventilatory and cerebral circulatory responsiveness to CO2 indicate that the brain is less well defended against hypercapnia in liver failure, and these changes are especially unfavourable as cerebral function deteriorates when the PCO2 is increased.
Clin Sci Mol Med 1975 Aug
PMID:Effect of liver failure on the response of ventilation and cerebral criculation to carbon dioxide in man and in the goat. 23 83

Oxygen dissociation curve and adenosine triphosphate (ATP) and 2,3-diphosphoglycerate (DPG) contents in red blood cells (RBC) were determined in canine blood stored in acid citrate dextrose (ACD) and citrate phosphate dextrose (CPD) solutions. The oxygen-unloading ability decreased, as shown by the left shift of oxygen dissociation curve during storage, and the shift correlated with decreasing DPG but not decreasing ATP concentrations. After 2 weeks of storage in ACD solution, oxygen dissociation curves were shifted significantly to the left. For blood stored in CPD solution, 4 weeks was required before the shift was significant. It was concluded that canine blood collected and stored in CPD solution is more efficient than that stored in ACD solution in delivering oxygen to the tissues.
J Am Vet Med Assoc 1975 Jul 01
PMID:Effect of storage on oxygen dissociation of canine blood. 23 23

In 50 healthy mothers scheduled for elective Caesarean section, anaesthesia was induced with propanidid (7 mg/kg body weight). Thereafter, ventilation was controlled with nitrous oxide, oxygen and muscle relaxants. A further dose of propanidid (1 mg/kg body weight) was administered 3 minutes after the initial injection of this drug, as a means of preventing maternal awareness during equilibration with the anaesthetic gas mixture. The acid-base status of the mothers before the induction of anaesthesia, and at delivery, revealed a mild degree of respiratory alkalosis with a compensatory metabolic acidosis. Umbilical cord blood gas results indicated the presence of significant fetal acidosis, both respiratory (mean pCO2 Uv 46,3 torr (SD 11,3) and Ua 54,3 torr (SD 12,0)), and metabolic (mean base excess Uv-9 mEq/l (SD 4,2) and Ua-11,8 mEq/l, (SD 5,0)) in origin. The average umbilical cord blood oxygen tensions were Uv 25,9 torr (SD 10), and Ua 15,4 torr (SD 8,5); mean maternal to fetal base-excess gradients were Ma-Uv 4,1 mEq/l (SD 2,8) and Ma-Ua 6,5 mEq/l (SD 3,5). Five mothers (10%) offered convincing evidence of factual recall during surgery, and 3 of these were aware of pain. Nausea and vomiting occurred in 5 patients and in 4 there were clinical signs of postoperative chest infection. The degree of fetal biochemical asphyxia, and the incidence of maternal awareness during surgery, were significantly greater than previously reported when thiopentone was used for the induction of anaesthesia for Caesarean section. The results obtained are discussed, and the conclusion is drawn that propanidid for anaesthesia appears to offer no advantage over thiopentone in obstetric practice.
S Afr Med J 1975 Aug 02
PMID:Propanidid for anaesthetic induction at Caesarean section. 23 56


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