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Biomedical subjects

D Lichtenberg

Publications and source records attributed to D Lichtenberg.

At least 91 records · Page 5Linked to original sources

Effect of surface curvature on stability, thermodynamic behavior, and osmotic activity of dipalmitoylphosphatidylcholine single lamellar vesicles.

The size and surface curvature dependence of the properties and stability of single lamellar vesicles have been investigated by using a variety of physicochemical techniques. Dipalmitoylphosphatidylcholine single lamellar vesicles of sizes ranging between 200 and 900 A in diameter have been prepared by the French press method and characterized with respect to their size distribution, stability, and thermotropic behavior by negative stain electron microscopy, molecular sieve chromatography, nuclear magnetic resonance spectroscopy, and differential scanning calorimetry. Vesicles with a diameter smaller than 400 A are unstable below their transition temperature and fuse spontaneously to form larger single lamellar vesicles. Correlation analysis of experimentally obtained size distributions and calorimetric phase transitions profiles allowed estimation of the size dependence of the transition temperature. The phase transition temperature depends on the vesicle size in a sigmoidal fashion. Throughout the entire 200-700 A diamter range, the phase transition parameters are sensitive to size; however, the size dependence is especially pronounced around 400 A in diameter. The anomalous size dependence of the transition temperature for vesicles smaller than 400 A in diameter has been attributed to a decrease in the effective bilayer curvature due to packing rearrangements of the lipid molecules. Changes in the fractional degree of self-quenching of trapped 6-carboxyfluorescein induced by osmotic stress indicate that large single lamellar vesicles are not spherical under isoosmotic conditions. These vesicles are relatively flexible and can sustain almost a 2-fold increase in their internal aqueous volume without any leakage of the internal content.

Drug Stability↗

Relationship between the activity of pancreatic phospholipase A2 and the physical state of the phospholipid substrate.

When pancreatic phospholipase A2 is mixed with small unilamellar vesicles made from dipalmitoyl phosphatidylcholine at or above the phase transition temperature (tm), the time course of hydrolysis exhibits a distinct lag period. On the other hand, if the enzyme is preincubated with substrate for a short period of time below the transition temperature (during which time only limited hydrolysis occurs) and then assayed at high temperature, no lag period is observed. This phenomenon does not appear to be the result of product formation. Instead, the reported results lend substantial support to the hypothesis that a relatively slow substrate-enzyme organizational step is required as part of an activation process and this is most rapid when the substrate is in the gel state. However, the intrinsic activity (after the initial step of activation) is maximal when the substrate is in the liquid-crystalline state.

Animals↗

A large outbreak of infections caused by a strain of Staphylococcus aureus resistant of oxacillin and aminoglycosides.

An extensive outbreak of nosocomial infections caused by oxacillin- and aminoglycoside-resistant Staphylococcus aureus (OARSA) occurred over a 16 month period. A total of 349 isolates of OARSA were obtained from 174 patients. Colonization with OARSA was found in 92 patients. There was 120 infections in 82 patients; 50 were surgical wound infections, 13 were nonsurgical wound infections, six were pneumonias, 15 were urinary tract infections, 12 were intravenous site infections, and there were 19 episodes of bacteremia (seven transient, 12 persistent). In patients with persistent bacteremia, the mortality rate was 33 percent. In patients treated for persistent bacteremia with vancomycin, the survival rate was 80 percent. Infections were highly associated with the surgical intensive care unit, and 90 percent of the isolates of OARSA tested had the same phage-type. Elderly patients with significant underlying disease, a history of previous surgery or of prior antimicrobial therapy appeared to be at increased risk for OARSA infections. OARSA were resistant to multiple antibiotics besides oxacillin, but all isolates were sensitive to vancomycin and rifampin. Three surgical intensive care unit nurses were found to be nasal carriers of OARSA, and one nurse had dermatitis of both hands colonized with OARSA. Following the removal of these nurses from the surgical intensive care unit and the institution of strict infection control measures, the number of OARSA infections and colonizations decreased to less than one per month. OARSA produces serious nosocomial disease, and epidemiologic intervention was effective in controlling this outbreak.

Adult↗

Enteral administration of insulin in the rat.

1 The effect of the surfactant, Cetomacrogol 1000, on the absorption of insulin across the rectal mucosa has been studied. 2 Rectal administration of microenemata containing Cetomacrogal 1000 and insulin causes a rise in the plasma concentration of insulin and a consequent fall in the blood glucose concentration in diabetic and non-diabetic rats. 3 The hypoglycaemic response is dependent on both the concentration of surfactant and the dose of insulin administered. 4 The results suggest that the transport of insulin across the rectal mucosa is facilitated by Cetomacrogal 1000.

Animals↗

Attenuation of the lithium-induced diabetes-insipidus-like syndrome by amiloride in rats.

The effect of amiloride on lithium-induced polydipsia and polyuria and on the lithium concentration in the plasma, brain, kidney, thyroid and red blood cells was investigated in rats, chronically treated with LiCl. Amiloride reduced the drinking and urine volume of rats in an acute (6 or 12 h) and a subacute (3 days) experiment. 6 h after the administration of amiloride, a reduction was observed in the lithium content of the renal medulla but not in the other organs studied. At 12 h, all the tissues showed a slight increase in lithium levels. After 3 days of combined treatment, a marked elevation in plasma and tissue lithium levels accompanied a reduction in water intake. In all the experiments, the attenuation of the lithium-induced diabetes-insipidus-like syndrome by amiloride was accompanied by a reduction of the ratio between the lithium concentration in the renal medulla and its levels in the blood and an elevation in the plasma potassium level. It is concluded that acute amiloride administration to lithium-treated patients suffering from polydipsia and polyuria might relieve these patients but prolonged amiloride supplementation would result in elevated lithium levels and might be hazardous.

Amiloride↗

Dependence of the conformation of the polar head groups of phosphatidylcholine on its packing in bilayers. Nuclear magnetic resonance studies on the effect of the binding of lanthanide ions.

Proton magnetic resonance spectra of vesicles of various sizes composed of egg phosphatidylcholine (PC) with varying concentrations of cholesterol differed in the apparent line width of the signal of the methylene protons of PC (delta v1/2). They also varied in the extent of lanthanide-induced shifts of the 31P and 1H NMR signals of the corresponding nuclei of the polar head groups located on the outer surface of the vesicles (delta delta). The differences in the lanthanide-induced shifts of the 31P signals are fully accounted for by the ratio between the externally added lanthanide and the number of PC head groups available for interaction with the lanthanide ions. This was not the case ofr the changes in the 1H NMR spectra. Here delta delta decreased with increasing delta v1/2, suggesting that the packing of the PC paraffinic chaings in the bilayer affects the conformation of the polar head groups; tightening of the packing probably results in a more extended conformation of the head groups. This conclusion is also supported by the larger effect lanthanides have on the 1H chemical shift of the choline head groups on the outer surface of small unilamellar vesicles as compared to groups on the inner, tighter packed layer.

Chemical Phenomena↗

Structural and kinetic studies on the solubilization of lecithin by sodium deoxycholate.

Mixed dispersions of egg phosphatidylcholine (PC) and the bile salt sodium deoxycholate (DOC) were prepared by various methods, and their turbidities and proton magnetic resonance spectra were studied as a function of time. The spectra of dispersions prepared by dissolving both components in a common organic solvent and replacing the organic solvent by water did not change with time, indicating that the mixed aggregates formed represent "a state of equilibrium". In the 1H NMR spectra of these mixed aggregates, only signals from small mixed micellar structures were narrow enough to be observed. The dependence of the NMR line widths on the molar ratio of DOC to PC (R) is interpreted in terms of a model for the PC--DOC mixed micelles, according to which PC is arranged as a curved bilayer, the curvature of which increases with increasing R. Upon mixing PC with aqueous solutions of DOC, we found that the mixed aggregates formed are slowly reorganized and ultimately reach the same state of equilibrium. This reorganization was found to be a pseudo-first-order process, the rate constant of which depends linearly upon the detergent concentration. This process involves saturation of the outer bilayers of the multilamellar PC by detergent, followed by transformation of these bilayers into mixed micelles. It is concluded that the solubilization occurs through consecutive "peeling off" of lecithin bilayers.

Deoxycholic Acid↗

The use of phospholipid liposomes for lithium administration. Polydipsic effect and tissue distribution of lithium.

Administration of lithium entrapped in phospholipid liposomes increased the lithium-induced polydipsia, but did not accelerate the onset of this effect. It also resulted in a larger accumulation of lithium in the liver, kidney and spleen, but not in the brain. The time course of polydipsia suggests that it depends on the intracellular lithium concentration. However, the rate of development of this effect depends on some additional factor.

Animals↗

The interpretation of proton magnetic resonance linewidths for lecithin dispersions. Effect of particle size and chain packing.

Two previously reported theoretical treatments of the effect of sonication on the PMR spectrum of phospholipid bilayer membranes have led to divergent conclusions regarding the effects of sonication on the structure of the bilayer membrane. In this report these two theoretical treatments will be critically reviewed, and it will be shown that only the theory of Seiter and Chan (Seiter, C.H.A. and Chan, S.I. (1973) J. Am. Chem. Soc. 95, 7541-7553) yields predictions which are in agreement with experiment. Analysis of available and newly acquired NMR results for sonicated bilayer vesicles of different sizes, both above and below the thermal phase transition, indicates that sonication does disrupt the regular molecular packing of the phospholipid molecules in these systems.

Binding Sites↗