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Biomedical subjects

M J Ostro

Publications and source records attributed to M J Ostro.

16 recordsLinked to original sources
PubMed1989

Use of liposomes as injectable-drug delivery systems.

The formation of liposomes and their application as delivery systems for injectable drugs are described. Liposomes are microscopic vesicles composed of one or more lipid membranes surrounding discrete aqueous compartments. These vesicles can encapsulate water-soluble drugs in their aqueous spaces and lipid-soluble drugs within the membrane itself. Liposomes release their contents by interacting with cells in one of four ways: adsorption, endocytosis, lipid exchange, or fusion. Liposome-entrapped drugs are distributed within the body much differently than free drugs; when administered intravenously to healthy animals and humans, most of the injected vesicles accumulate in the liver, spleen, lungs, bone marrow, and lymph nodes. Liposomes also accumulate preferentially at the sites of inflammation and infection and in some solid tumors; however, the reason for this accumulation is not clear. Four major factors influence liposomes' in vivo behavior and biodistribution: (1) liposomes tend to leak if cholesterol is not included in the vesicle membrane, (2) small liposomes are cleared more slowly than large liposomes, (3) the half-life of a liposome increases as the lipid dose increases, and (4) charged liposomal systems are cleared more rapidly than uncharged systems. The most advanced application of liposome-based therapy is in the treatment of systemic fungal infections, especially with amphotericin B. Liposomes are also under investigation for treatment of neoplastic disorders. Liposomes' uses in cancer therapy include encapsulation of known antineoplastic agents such as doxorubicin and methotrexate, delivery of immune modulators such as N-acetylmuramyl-L-alanine-D-isoglutamine, and encapsulation of new chemical entities that are synthesized with lipophilic segments tailored for insertion into lipid bilayers. Liposomal formulations of injectable antimicrobial agents and antineoplastic agents already are undergoing clinical testing, and most probably will receive approval for marketing in the early 1990s. Liposomal encapsulation of drugs represents a new drug delivery system that appears to offer important therapeutic advantages over existing methods of drug delivery.

Drug Carriers↗
PubMed1988

The captured volume of multilamellar vesicles.

Characterization of classical 'hand-shaken' multilamellar lipid vesicles (MLVs) confirmed that these systems exclude solute during formation thus confounding previous captured volume measurements which typically have utilized solute as a merker of the occluded aqueous space. We used solvent rather than solute to determine the captured volume of these systems and obtained values at least twice those previously reported. We present here a captured volume and lamellarity profile of 'hand-shaken' MLVs and suggest that these parameters are dependent on the lipid concentration present during hydration.

Electron Spin Resonance Spectroscopy↗
PubMed1987

Pharmacodynamics and pharmacokinetics of parenteral histamine (H2)-receptor antagonists.

Parenteral histamine (H2)-receptor antagonists are frequently used to prevent upper gastrointestinal bleeding caused by stress-induced gastric mucosal damage in critically ill patients. It is generally agreed that the goal of therapy in this syndrome is the consistent elevation of gastric pH levels above a certain value, often set at 4, in order to prevent the underlying mucosal damage from progressing to bleeding. The three H2-receptor antagonists currently available in a parenteral form and suitable for this mode of prophylaxis are cimetidine, ranitidine, and famotidine. The pharmacodynamic and pharmacokinetic properties of these agents, as they relate to their use in prevention of stress ulceration bleeding, are discussed here. These agents are more noted for their pharmacodynamic and pharmacokinetic similarities in acid suppression, elimination, and metabolism than for their differences. Ranitidine and famotidine are more potent than cimetidine, and famotidine has a slightly longer half-life than do cimetidine and ranitidine, but current dosing recommendations take these differences into account so that the agents have equivalent efficacy. Cimetidine and ranitidine have been widely used in this application. Less experience has been obtained, to date, with famotidine. Recent studies with primed, continuous infusions of cimetidine indicate that dosing schedule may be the key to obtaining better efficacy in prophylaxis of stress-related mucosal damage. Similar studies with ranitidine have not yielded results as promising as those with cimetidine, however, and few data are available on famotidine.

Gastric Acid↗
PubMed1987

Liposomes.

Explore the source record for details and available documents.

Amphotericin B↗
PubMed1985

Novel multilayered lipid vesicles: comparison of physical characteristics of multilamellar liposomes and stable plurilamellar vesicles.

The preparation of a new kind of multilayered liposome, called a stable plurilamellar vesicle (SPLV), is described. Although SPLVs and classical multilamellar vesicles (MLVs) are made of the same materials and appear overtly similar in the electron microscope, the two types of vesicles differ as determined by stability, entrapment efficiency, electron spin resonance (ESR), NMR, X-ray diffraction, and biological effects. It is demonstrated that, contrary to what has been assumed, classical MLVs exclude solutes during their formation and, thus, are under a state of osmotic compression. By contrast, the SPLV process produces liposomes that are not compressed. The effects of osmotic compression are discussed. It is suggested that the state of osmotic stress is an important variable that distinguishes various types of liposomes and that has significant physical and biological consequences.

Anti-Bacterial Agents↗
PubMed1985

Control of gastric pH with cimetidine: boluses versus primed infusions.

Previous studies suggest that antacids are more effective than intravenous cimetidine in maintaining the gastric pH above 4.0 in acutely ill patients. We hypothesized that this was because blood levels of cimetidine are not sustained at therapeutic levels with the bolus doses. The purpose of this study was to compare gastric pH and serum cimetidine levels when cimetidine was administered as bolus versus infusion. We studied 23 acutely ill patients who received intravenous cimetidine given as boluses and primed infusions. The gastric pH could be maintained above 4.0 with infusions of up to 50 mg/h (1200 mg/day) in 20 patients, compared with only 5 patients with bolus administrations of up to 300 mg every 6 h (1200 mg/day). The differences in ability to maintain the gastric pH above 4.0 were entirely due to the reduced ability of bolus infusion to maintain an adequate serum level. Neither technique could maintain the pH above 4.0 in 3 patients, all of whom had received cimetidine recently. A gastric pH greater than 4.0 correlated directly with a therapeutic serum cimetidine level. We conclude that infusions of cimetidine are better able to sustain therapeutic blood levels and, therefore, are superior to bolus cimetidine in maintaining gastric pH above 4.0. Some patients, however, may not respond to cimetidine even if therapeutic levels are achieved and may require supplemental antacids.

Adult↗
PubMed1985

Vitamin E and selenium status of patients receiving short-term total parenteral nutrition.

In a prospective protocol, plasma tocopherols, selenium (Se), Se-dependent glutathione peroxidase, platelet aggregation and erythrocyte hemolysis were measured in 23 control subjects, and 15 patients receiving total parenteral nutrition (TPN), before and after 2 wk of TPN unsupplemented with vitamin E and Se. The results indicate that short-term TPN did not alter status of these nutrients. However, TPN patients had significantly lower plasma levels of Se (p less than 0.01) and alpha-tocopherol (p less than 0.01) relative to control subjects. Low plasma levels, with no attendant decrease in function, suggest a marginal depletion. In view of this, and considering the low amount of vitamin E and Se supplied by the TPN solutions, supplementation with these nutrients is recommended.

Adolescent↗
PubMedDate not supplied

Total parenteral nutrition and complete bowel rest in the management of Crohn's disease.

The role of parenteral nutrition with complete bowel rest in the management of active Crohn's disease was evaluated retrospectively in 100 patients who were otherwise refractory to conventional medical management. Ninety patients received complete nutrient replacement and 10 received protein-sparing therapy. In 77 patients, a clinical remission was achieved. Analysis of subgroups revealed that the remission rate was equivalent in patients with subacute bowel obstruction (76%), inflammatory mass (82%), and otherwise uncomplicated severe active disease (89%). However, those patients with fistulae responded less well (63%). The location of the intestinal involvement with the disease did not influence the remission rate (73% in those with small bowel disease only and 78% in those with combined small and large bowel disease). All six patients with only large bowel involvement achieved a remission. In 81% of those patients with a remission, no corticosteroids were given, or the dose prior to TPN was maintained. The serum albumin improved significantly (p less than 0.001) from 3.2 +/- 0.1 to 3.6 +/- 0.1 g/dl with total parenteral nutrition, but there was no significant effect on the hematocrit (p greater than 0.5). The percentage of patients still in remission after 3 months and 1 yr of follow-up was 75 to 79 and 58 to 61%, respectively, in the three nonfistulous groups, and 46 and 36%, respectively, in those with fistulous disease. Thus total parenteral nutrition with complete bowel rest appears to be an effective therapeutic modality in the primary management of complicated Crohn's disease.

Abdomen↗
PubMedDate not supplied

Selenium and vitamin E stability in parenteral solutions.

Stability of alpha-tocopherol acetate and selenium in amino acid/dextrose solutions with SoluZyme or MVI-1000 vitamin injections was evaluated following exposure to fluorescent lighting and room temperature, and after flowing through an infusion apparatus. The stability of selenium in parenteral solutions for a 10-wk period was also determined. In each condition no significant loss of alpha-tocopherol acetate or selenium was observed. It was concluded that alpha-tocopherol acetate and selenium as selenious acid are stable in parenteral solutions and no significant loss occurs during delivery to patients.

Drug Stability↗