Search PubMed⌕ Search

Biomedical subjects

S B Hall

Publications and source records attributed to S B Hall.

32 records · Page 2Linked to original sources
PubMed1992

Inhibition of pulmonary surfactant by oleic acid: mechanisms and characteristics.

The inhibitory effects of oleic acid (OA) on the surface activity of pulmonary surfactant were characterized by use of the oscillating bubble surfactometer, the Wilhelmy balance, and excised rat lungs. Oscillating bubble studies showed that OA prevented lavaged calf surfactant [0.5 mM phospholipid (PL)] from lowering surface tension below 15 mN/m at or above a molar ratio of OA/PL = 0.5. In contrast to inhibition of surfactant by plasma proteins, increasing the surfactant concentration did not eliminate inhibition by oleic acid, which occurred at OA/PL greater than 0.67 on the oscillating bubble even at surfactant concentrations of 1.5 and 12 mM PL. Studies of surfactant adsorption showed that preformed films of OA had little effect on the adsorption of pulmonary surfactant. Wilhelmy balance studies showed that OA did interfere with the ability of spread films of surfactant to reach low surface tensions during dynamic compression. Further balance experiments with binary films of OA and dipalmitoyl phosphatidylcholine showed that these compounds were miscible in surface films. Together these findings suggested that OA inhibited pulmonary surfactant activity by disrupting the rigid interfacial film responsible for the generation of very low surface tension during dynamic compression. Mechanical studies in excised rat lungs showed that instillation of OA gave altered deflation pressure-volume characteristics with decreased quasi-static compliance, indicating disruption of pulmonary surfactant function in situ. This alteration of mechanics occurred without major changes in the composition of lavaged PLs or in the tissue compliance of the lungs defined by mechanical measurements during inflation-deflation with saline.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Importance of hydrophobic apoproteins as constituents of clinical exogenous surfactants.

The biophysical properties and physiologic effects of a series of clinical exogenous pulmonary surfactants was compared to determine the importance of the hydrophobic apoproteins (SP-B and C) as constituents of these preparations. The three exogenous surfactants studied, calf lung surfactant extract (CLSE), Survanta (Surfactant-TA), and Exosurf, all contain dipalmitoyl phosphatidylcholine (DPPC) as their major constituent. CLSE and Survanta also contain 1 to 2% of SP-B,C but Exosurf has the additives hexadecanol and tyloxapol instead to enhance the activity of DPPC. In adsorption experiments, CLSE reached a final surface tension of 22 mN/m, and Survanta and Exosurf reached 28 and 38 mN/m, respectively. Addition of 1% by weight of an apoprotein isolate containing both SP-B and C to Exosurf slightly improved its adsorption. In oscillating bubble studies, CLSE and Survanta decreased surface tension to low values of less than 1 and 2 mN/m, respectively, but Exosurf achieved a minimum value of only 29 mN/m. Addition of SP-B,C to Exosurf improved this minimum to 1 mN/m and approached the behavior of mixtures of synthetic DPPC with SP-B,C. In both adsorption and pulsating bubble experiments, the minimum surface tensions found for Exosurf were almost identical to those generated by tyloxapol alone. In studies of physiologic activity, 20 mg of CLSE or Survanta restored the pressure-volume mechanics of lavaged, surfactant-deficient excised rat lungs to 95 and 50%, respectively, of normal prelavage levels. Instillation of Exosurf (37.5 mg) produced a minimal improvement of only 10% compared to 70% for mixtures containing 1% SP-B,C with either Exosurf or DPPC.(ABSTRACT TRUNCATED AT 250 WORDS)

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1990

Hydrophobic homopolymeric peptides enhance the biophysical activity of synthetic lung phospholipids.

The effects of homopolymeric amino acids (molecular weight 2300 to 14,000) on the surface activity of dipalmitoyl phosphatidylcholine (DPPC) and DPPC/egg-phosphatidylglycerol (PG) were characterized by adsorption and dynamic surface tension lowering measurements at 37 degrees C. Homopolyamino acids studied included poly-L-leucine (poly-Leu) and poly-L-valine (poly-Val), since Leu and Val are known to be prominent in the structure of hydrophobic lung surfactant apoprotein SP-B and SP-C. In addition, several other homopolyamino acids with varying hydrophobicity index were also investigated, including poly-L-phenylalanine (poly-Phe), poly-L-serine (poly-Ser), poly-L-lysine (poly-Lys) and poly-L-glutamic acid (poly-Glu). Results showed that hydrophobic poly-Leu and poly-Phe at 1 and 10 weight percent greatly increased the adsorption facility of DPPC and DPPC/PG mixtures, with maximum surface pressures (up to 49 mN/m) near the equilibrium limit for phospholipid systems. In oscillating bubble studies, 1% mixture of poly-Leu or poly-Phe with DPPC or 8:2 DPPC/PG lowered surface tension into the range (near 1 mN/m) associated with active lung surfactant. In contrast, mixtures of DPPC and DPPC/PG with the more hydrophilic peptides poly-Ser, poly-Lys and poly-Glu showed little or no enhancement of surface activity over the phospholipids alone. Mixtures of poly-Val and phospholipids did not combine well with the simple co-sonication procedure used, and also exhibited little improvement in surface activity.(ABSTRACT TRUNCATED AT 250 WORDS)

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1990

Enhancement of biophysical activity of lung surfactant extracts and phospholipid-apoprotein mixtures by surfactant protein A.

The effects of surfactant protein (SP)-A on the dynamic surface tension lowering and resistance to inhibition of dispersions of calf lung surfactant extract (CLSE) and mixtures of synthetic phospholipids combined with SP-B,C hydrophobic apoproteins were studied at 37 degrees C and rapid cycling rate (20 cycles/min). Addition of SP-A to CLSE, which already contains SP-B and -C, gave a slight improvement in the time course of surface tension lowering on an oscillating bubble apparatus in the absence of inhibitory protein molecules such as albumin or hemoglobin. However, when these proteins were present at concentrations of 10-50 mg/ml, SP-A substantially improved the resistance of CLSE to their inhibitory effects. The beneficial effect of SP-A required the presence of Ca2+ ions, and disappeared when EDTA was substituted for this divalent cation in the subphase. The effect was also retained when SP-A was heated to 50 degrees C prior to addition to CLSE, but was abolished by heating SP-A to 99 degrees C. Additional studies showed that similar improvements in resistance to inhibition were found when SP-A was added to synthetic mixtures of dipalmitoyl phosphatidylcholine (DPPC):egg phosphatidylglycerol (PG) (80:20 by weight) reconstituted with 1% SP-B or SP-B and -C, but not to phospholipid mixtures containing only SP-C. The requirements for SP-B and calcium for the beneficial effects of SP-A on surface activity suggest that the formation of ordered, larger phospholipid-apoprotein aggregates may be involved in the process. The finding that SP-A enhances the ability of CLSE and other surfactant mixtures containing SP-B to resist inhibition is an advantage that will need to be weighed against other factors such as increased antigenicity and heat sensitivity in therapeutic applications in surfactant replacement therapy.

Amino Acid Sequence↗
PubMed1990

Altered function of pulmonary surfactant in fatty acid lung injury.

To determine whether acute fatty acid lung injury impairs pulmonary surfactant function, we studied anesthetized ventilated rabbits given oleic acid (55 mg/kg iv, n = 11) or an equivalent volume of saline (n = 8). Measurements of pulmonary mechanics indicated a decrease in dynamic compliance within 5 min of injury and a decrease in lung volume that was disproportionately large at low pressures, consistent with diminished surfactant activity in vivo. Bronchoalveolar lavage fluid obtained 1 h after injury had significantly increased erythrocytes and total leukocytes, largely polymorphonuclear cells. The phospholipid content and composition of the cell-free fraction had only minor changes from those of controls, but the protein content was increased 35-fold. Measurements of lavage surface activity in vitro showed an increase in average minimum surface tension from 1.3 +/- 0.4 (SE) dyn/cm in controls to 20.2 +/- 3.9 dyn/cm in injured animals. The alterations in static pressure-volume curves and decrease in lavage surface activity suggest a severe alteration of surfactant function in this form of lung injury that occurs despite the presence of normal amounts of surfactant phospholipids.

Animals↗
PubMed1990

Parenteral nutrition. Pharmaceutical problems of compatibility and stability.

A typical All-in-One (AIO) parenteral nutrition mixture in a 3-litre polymeric infusion bag will consist of lipid emulsion, amino acids, glucose, electrolytes, trace elements and vitamins. This varied mixture of chemical entities provides the potential for a number of chemical and physicochemical interactions that can compromise the clinical safety and efficacy of the product. The destabilisation of the lipid emulsion in the presence of electrolytes is a major problem. Although a predictive equation for the maximum concentrations of mono-, di- and trivalent ions causing instability has been proposed, it is too simplistic to be of significant value. The reasons for this are discussed as well as the stability implications of other additives to the parenteral nutrition mixture.

Drug Incompatibility↗
PubMed1985

Seronegative polyarthritis in giant cell arteritis.

Nineteen of 520 patients with biopsy-proven giant cell arteritis were found to have persistent seronegative, symmetric polyarthritis with a mean joint count of 20 (swollen plus tender). In 9 patients in the onset of polyarthritis occurred prior to the diagnosis of giant cell arteritis, 3 had simultaneous onset, and 7 developed polyarthritis within 3 years after the onset of giant cell arteritis. Ten of the 19 patients demonstrated radiographic features of joint space narrowing and/or erosions. In 1 patient in a synovial biopsy was performed, revealing marked multinucleated giant cell infiltration. A persistent seronegative polyarthritis, although uncommon in giant cell arteritis, may be its presenting symptom. Other symptoms of giant cell arteritis should be sought in patients who exhibit this feature, especially in those whose arthritis begins at age 50 or older.

Aged↗
PubMed1982

A method for hydrolyzing and determining the amino acid compositions of picomole quantities of proteins in less than 3 hours.

A method is described for quantitatively hydrolyzing proteins in 45 min and for analyzing the hydrolysates by high-performance liquid chromatography in an additional 52 min. The alpha-amino acids were detected by the fluorescence of their omicron-phthaldialdehyde derivatives. Ten picomoles of each of the commonly occurring alpha-amino acids could be reliably determined. The method described yielded OPA-ethanethiolamino acid derivatives that were stable for 1 1/2 h and the HPLC method produced a better separation than previously published methods.

Amino Acids↗
PubMedDate not supplied

Biophysical inhibition of synthetic phospholipid-lung surfactant apoprotein admixtures by plasma proteins.

Biophysical activity and inhibition characteristics were studied for a series of synthetic surfactants composed of purified bovine lung surfactant proteins (SP)-B or -C combined with dipalmitoyl phosphatidylcholine (DPPC) and egg-phosphatidylglycerol (PG) in a weight ratio of 80:20:1 DPPC/PG/protein. Surfactant protein preparations included two isolates of SP-B, confirmed by amino terminal sequence analysis, three isolates of SP-C which were free of SP-B by ELISA and Western blot analysis, and two isolates containing both SP-B and -C. In oscillating bubble studies, mixtures of phospholipids with isolates containing pure SP-B or both SP-B and -C lowered surface tension to less than 1 mN/m within 2 min of pulsation at both 1.25 mg/ml and 2.5 mg/ml. Phospholipids combined with isolates of pure SP-C also had substantial activity, lowering surface tension to between 1 mN/m and 3 mN/m depending on the SP-C preparation used. The surface activity of synthetic phospholipid-apoprotein admixtures was decreased significantly by the plasma proteins albumin and fibrinogen, but with varying characteristics depending on the apoprotein preparation involved. At 1.25 mg/ml phospholipid, admixtures containing either isolate of SP-B were inhibited by 10 mg/ml of plasma proteins, as were those with one of the SP-C preparations. However, admixtures containing the two other pure SP-C preparations were not inhibited until 20-50 mg/ml of albumin or fibrinogen were present. The highest resistance to inhibition was shown by admixtures containing one of the apoprotein isolates having both SP-B and -C.(ABSTRACT TRUNCATED AT 250 WORDS)

1,2-Dipalmitoylphosphatidylcholine↗
PubMedDate not supplied

PARSAFE: computer program for safety assessment and optimization of parenteral nutrition formulations based on chemical speciation analysis.

Instability arising from the formation of precipitates and lipid emulsion aggregates is common in parenteral nutrition formulations due to the concentration- and pH-dependent incompatibility of some of the vital ingredients. Previously, the boundaries between stability and instability could only be established through the use of laborious and expensive empirical methods. The predictive technique with the concept of chemical speciation (based on the analysis of many competitive thermodynamic equilibriums) has been adapted for use with parenteral fluids so that these detrimental events may now be avoided. A comprehensive computer program, PARSAFE ((C) 1991. Sponsors interested in this program should contact D.R.W.) has been developed for this purpose. PARSAFE encompasses chemical-speciation techniques and contains a large data base of commonly used intravenous fluid constituents together with the appropriate thermodynamic equilibrium constants describing their interactions so that stability prediction may be readily achieved in hospital pharmacy laboratories. We review the relevant physical chemistry required for the successful implementation of PARSAFE and outline the audit trails involved in the development of the predictive model.

Algorithms↗