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Biomedical subjects

S S Davis

Publications and source records attributed to S S Davis.

At least 163 records · Page 9Linked to original sources
PubMed1990

Nasal absorption enhancers for biosynthetic human growth hormone in rats.

The effects of several prospective absorption enhancers were assessed on the nasal absorption of biosynthetic human growth hormone (hGH) in the rat. These enhancers function by alternative mechanisms that include enzyme inhibition, reduction in mucus viscosity, and enhancement of membrane fluidity. The levels of plasma hGH achieved were determined by an enzyme-linked immunosorbent assay. The increase in peak height was calculated relative to nasal administration of hGH alone without any enhancers and the relative bioavailability was calculated with reference to subcutaneous injection data. A lysophospholipid, lysophosphatidylcholine, gave the highest peak concentration, with an increase in peak height of 450% and a relative bioavailability of 25.8%. However, the greatest increase in AUC (291%) was achieved with the aminopeptidase inhibitor, amastatin, which gave a relative bioavailability of 28.9%. A mucolytic agent, N-acetyl-L-cysteine, and a transmembrane fatty acid transporter, palmitoyl-DL-carnitine, were also found to promote the nasal absorption of hGH in this model, with relative bioavailabilities of 12.2 and 22.1%, respectively. Bestatin, an enzyme inhibitor, was not an effective absorption enhancer for hGH in this model.

Absorption↗
PubMed1990

Transdermal delivery of theophylline to premature infants using a hydrogel disc system.

1. Preterm infants show incompletely developed skin with reduced barrier function. The possibility of transdermal delivery of theophylline from hydrogel discs swollen with choline theophyllinate has been investigated. 2. Drug loaded hydrogel discs 2 cm2 in area were applied to the abdomen and occluded. Serum theophylline concentrations were measured in twenty-one infants of less than 31 weeks gestation. 3. Therapeutic concentrations were achieved in 18 individuals, and maintained for up to 15 days after repeated application of discs. A correlation between maximum serum drug concentration and transepidermal water loss, gestation and birthweight was demonstrated.

Administration, Cutaneous↗
PubMed1990

Secondary hypogonadism in older men: its relation to impotence.

The relation of the reproductive endocrine system to impotence in older men was examined by measuring the concentrations of testosterone (T), bioavailable testosterone (BT), LH, and PRL and body mass index (BMI) in 57 young controls (YC), 50 healthy potent older controls attending a health fair (HF), and 267 impotent patients (SD). The SD and HF had markedly reduced mean T and BT values compared to YC. When adjusted for age and BMI there was no difference in BT between potent and impotent older men. The percent BT was much higher in YC than in the older groups. While the percent BT rose significantly with increased T in YC, it was inversely related to T in the older subjects, suggesting that increased sex hormone-binding globulin binding was a primary event leading to a low BT. Forty-eight percent of HF and 39% of SD were hypogonadal, as defined by a mean BT of 2.5 SD or more below the mean of YC (less than or equal to 2.3 nmol/L). Ninety percent of these had LH values in the normal range, suggesting hypothalamic-pituitary dysfunction. Thirty-four SD and six each of YC and older control volunteers (OC) underwent GnRH testing. Older subjects showed impaired responsiveness to GnRH compared to YC. A low basal LH level correlated very highly with hyporesponsiveness to GnRH. Thus, secondary hypogonadism and impotence are two common, independently distributed conditions of older men.

Aged↗
PubMed1990

Physiopathological and physicochemical considerations in targeting of colloids and drug carriers to the bone marrow.

The ability of the bone marrow to remove particulate matters from the circulation, opens up perhaps an opportunity for the delivery of therapeutic agents by means of colloidal drug carrier systems such as liposomes, emulsions, nanoparticles, etc. for the treatment of diseases and disorders of this multifunctional organ of the body. This article is designed to provide a critical review on fundamentals, problems, current progress, and future prospects of site-specific delivery of intravenously injected colloidal drug carriers to the bone marrow.

Animals↗
PubMed1989

Morphology of Golgi-impregnated neurons in hyperstriatum ventralis, pars caudalis in adult male and female canaries.

Golgi-impregnated neurons in the song control nucleus hyperstriatum ventralis, pars caudalis (HVc) in male and female canaries (Serinus canarius) have been divided into classes, primarily on the basis of interneuronal variability in spine density and dendritic branching pattern. At least four neuronal classes are found in HVc: aspinous neurons and three classes of spiny neurons. The "furry" dendrite (FD) cell class consists of neurons with long dendrites that are densely packed with spines. Their cell bodies are between 10 and 15 microns in diameter. Neurons of the thick dendrite (TD) cell class also have long dendrites but only about half as many spines along their dendritic branches. Their cell bodies are between 12 and 18 microns in diameter. Neurons of the short dendrite (SD) cell class are characterized by a low spin density, very thin dendrites, and a small dendritic field. Their cell bodies are between 9 and 13 microns in diameter. The TD class can be divided into two subclasses on the basis of the shape of the dendritic field. Principal component factor analysis and cluster analysis provide objective support for this classification scheme. Neurons of subclass TD2 are sexually dimorphic. Neurons from males have dendritic trees that are about 70% larger and have 40% more dendritic endings than do neurons from females. There may also be small sex differences in dendritic morphology in the SD class and in the remainder of the TD class. There are clearly no sex differences in the dendritic morphology of neurons from the FD class. The direct pathway which is believed responsible for dimorphic song production in canaries is from HVc to nucleus robustus archistriatalis (RA) and then to the motor neurons which control the avian vocal organ. It is surprising that the most striking dimorphism in the present data occurs in neurons which, on morphological grounds, are unlikely to project to RA.

Animals↗
PubMed1989

Microparticles as potentially orally active immunological adjuvants.

A model microparticulate carrier system, capable of partially protecting an entrapped antigen against enzymatic degradation, has been successfully used to induce an enhanced secretory immune response to an incorporated model soluble antigen following oral administration to experimental rats. Ovalbumin was incorporated into polyacrylamide microparticles (2.55 microns diameter) and administered orally on four consecutive days to rats primed 14 days earlier by intraperitoneal injection. The memory secretory IgA antibody response (day 65) to the microparticle incorporated antigen group was significantly raised relative to a soluble antigen control group response (p less than 0.01), following administration of a booster dose of soluble antigen to both groups (day 61).

Acrylic Resins↗
PubMed1989

Poly(butyl-2-cyanoacrylate) particles as adjuvants for oral immunization.

The potential oral adjuvanticity of a colloidal carrier system for an adsorbed antigen was investigated and the effect of particle size of the carrier was partially determined. Ovalbumin was adsorbed onto poly(butyl-2-cyanoacrylate) particles of two different sizes and administered orally to rats previously primed by intraperitoneal injection. After 14 and 50 days, the secretory immune responses were significantly increased for animals gastrically intubated with ovalbumin adsorbed to 100 nm particles, relative to a control group response to soluble antigen.

Adjuvants, Immunologic↗
PubMed1989

Correlation of phenylpropanolamine bioavailability with gastrointestinal transit by scintigraphic monitoring of 111In-labeled hydroxypropylmethylcellulose matrices.

Two controlled-release hydroxypropylmethylcellulose (HPMC) matrix formulations, a single-unit and a multiple-unit system, have been evaluated in human volunteers. Both formulations contained the sympathomimetic drug phenylpropanolamine hydrochloride and each was radiolabeled with 111Inbound Amberlite IR 120 ion-exchange resin. The formulations were administered to each of six healthy male volunteers and gastrointestinal (GI) transit was monitored using a gamma camera. Serum samples were taken at set time intervals and assayed for phenylpropanolamine content, thus allowing blood drug levels to be correlated with the position of the dosage form in the GI tract. The multiple-unit system emptied from the stomach gradually over a period of about 180 min, when administered after a light breakfast, whereas the single-unit dosage forms had extremely variable gastric emptying times (range, 60 to greater than 570 min). However, both formulations provided prolonged phenylpropanolamine blood levels. The differences in the blood profiles obtained with the two formulations were attributed to variations in their in vitro release rates and not to any differences in their GI transit times.

Adult↗
PubMed1989

Review article: mechanisms of drug release from tablets and capsules. I: Disintegration.

Variable drug release from solid oral dosage forms has been an important cause of bioavailability problems in the past, and is a factor now carefully controlled in pharmaceutical products. In two reviews, we describe briefly the composition and manufacture of tablets and capsules, and the two main processes by which they release drugs; disintegration and dissolution. We will explain what is presently understood of the actual mechanisms of drug release and the physico-chemical factors that affect the release process. The strategies adopted by pharmaceutical scientists in designing modern oral solid dose forms to release drugs at reproducible and therapeutically optimal rates will be discussed. Finally, the role of gamma scintigraphy in assessing dosage form performance in vivo will be described.

Biological Availability↗
PubMed1989

Review article: mechanisms of drug release from tablets and capsules. 2. Dissolution.

Optimal drug dissolution is crucial to the success of oral drug therapy. Slow dissolution has frequently been correlated with poor or erratic performance of oral dosage forms in vivo, and drugs of low aqueous solubility provide a major challenge to the designer of modern oral dosage forms. In this second of two reviews, we briefly describe the physical process of dissolution, the principal factors controlling drug dissolution from tablets and capsules, and the strategies that are utilized by pharmaceutical scientists to enhance drug dissolution of orally administered drugs.

Animals↗
PubMed1989

The effect of Miglycol 812 oil on the oral absorption of propranolol in the rat.

This work has examined the effect of Miglyol 812 oil and its composite fatty acids on the oral absorption of propranolol with reference to its intravenous (i.v.) pharmacokinetics. Propranolol hydrochloride, spiked with 4-(3) H labelled compound, was administered i.v. or orally to male Wistar rats and blood concentrations of parent material determined by liquid scintillation counting after extraction into toluene. An i.v. dose-linearity study indicated dose-independent pharmacokinetics for propranolol at 1-2 mg kg-1, with a mean Cls, Vss, MRTi.v. and t0.5 beta of 0.076 L min-1 kg-1, 4.74 L kg-1, 57.81 min and 47.10 min, respectively. At 5 mg kg-1, there was evidence of non-linearity with MRTi.v. increased by about 250%, Vss by 170% and t0.5 beta by 230% compared with the lower doses. After oral administration of propranolol (10 mg kg-1) in aqueous solution, with or without Tween 80 (6%), the mean absorption time (MAT) and terminal half-life were approximately 55 min and 86 min, respectively. The MAT for propranolol administered in a 50% octanoic and lauric acid (1:1 by weight) oil-in-water emulsion, stabilized with 6% Tween 80 (129-90 min), was significantly longer compared with that for a 50% Miglyol 812 oil-in-water emulsion containing the same surfactant (16.55 min). The terminal half-life of propranolol administered in the fatty acid formulation (128.96 min), unlike that for the Miglyol emulsion (54-37 min), was significantly longer compared with that observed after i.v. administration (t0.5 beta = 47 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1989

Purification of pluronic F-68 for perfluorochemical emulsification.

A novel technique for purification of Pluronic F-68 has been developed involving passage through a silica-Amberlite resin column. Impurities present in commercial grade Pluronic could be readily removed, as confirmed by analysis of absorption and fluorescence emission bands. Intravenous injection of a 4% (w/v) unpurified Pluronic solution in male rats increased mean liver weight by 14% (P less than 0.05) after 24 h and increased spleen weight in female rats by 29% (P less than 0.01) after 7 days. No corresponding tissue weight changes occurred following injection of purified Pluronic solution. Haematocrit and red cell counts were also unchanged throughout. We propose that the use of purified Pluronic for perfluorochemical emulsification may reduce previously reported side-effects.

Animals↗
PubMed1989

Biweekly intracavernous administration of papaverine for erectile dysfunction.

To determine the efficacy of the intracavernous administration of papaverine hydrochloride every 2 weeks to treat male impotence, we recruited 50 patients from a sexual dysfunction clinic. Of these, 8 did not complete the course of papaverine therapy. A total of 8 had complications, including priapism in 3 and ecchymoses or urethral bleeding in 5. In 30 patients who had substantial vasculogenic disease, there was a notable improvement in the penile blood pressure after papaverine treatment, although only 9 reported successful sexual intercourse. The penile blood pressure in the remaining 12 patients without substantial vascular disease increased modestly after therapy, and 5 persons reported satisfactory sexual activity. We conclude that administering papaverine intracavernosally every 2 weeks improves sexual potency in a subset of sexually impotent patients. Those with severe vasculogenic disease and a penile-brachial pressure index of less than 0.65 are not good candidates for this regimen.

Adult↗
PubMed1989

Polyhydroxybutyrate as a drug carrier.

Polyhydroxybutyrate (PHB) can be used as an alternative polymer to polylactide-glycolides for drug carrier production. It is a linear homopolymer biosynthesized by various strains of bacteria by condensation of D(-)-B-hydroxybutyric acid and used as an energy and carbon source. PHB can be obtained by extraction from bacteria or by chemical synthesis. To be suitable as drug carrier the polymer has to be biocompatible, biodegradable in certain applications, and nontoxic. PHB seems to be biocompatible and biodegrades readily to carbon dioxide in bacteria; however, in humans, the reports are few and contradictory. The polymer is nontoxic and its monomer seems to be tolerated well in relatively high concentrations. Possible applications include implants and i.m.-administered particulates for controlled release and i.v.-injected colloidal carriers for drug targeting.

Animals↗
PubMed1989

Gastrointestinal transit of Sinemet CR in healthy volunteers.

The gastrointestinal transit and systemic absorption of Sinemet CR (50/200) and standard Sinemet (25/100) have been studied in fasting and "fed" healthy human subjects. Both formulations were labeled with a gamma-emitting radionuclide, and their gastric emptying, colon arrival, and in vivo dissolution profiles were monitored using gamma scintigraphy. The standard dosage forms were found to disperse soon after administration and to empty rapidly from both the fasting and the "fed" stomach. The erosion of the controlled-release (CR) system was independent of food. Dosing after a light breakfast altered the gastric emptying profile of the CR formulation and led to significant differences in the plasma levels of levodopa.

Antiparkinson Agents↗
PubMed1988

Polymeric microspheres as drug carriers.

The use of polymeric microsphere systems (including polypeptides) as vehicles for delivering drugs by a variety of routes is considered with particular reference to parenteral administration. Microsphere formulation is discussed with emphasis on the role of surface properties and how these can determine the fate of administered particles. Studies on the use of adsorbed block copolymers that can alter processes of protein uptake onto particle surfaces (opsonization) as well as the interaction of particles with macrophages (cell-particle adhesion) are described. Data are presented which show that by the selection of the appropriate coating material it is possible to direct particles within the body to sites such as the lung, liver, bone marrow, or to retain materials within the systemic circulation.

Adsorption↗