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At least 307 records · Page 17Linked to original sources
PubMed1993

IgG, IgM and IgA umbilical blood concentrations in normal singleton vaginal deliveries with stinking amniotic fluid or intrapartal maternal febrility > or = 38 degrees C or duration of delivery > 12 hours.

Total of 321 preterm/term newborns delivered in normal singleton vaginal deliveries was studied. Babies were divided into two groups. The first one includes 62 newborns with single, isolated clinical sign: stinking amniotic fluid or intrapartal maternal febrility > or = 38 degrees C or duration of delivery > 12 hours. The second one (control group) contained 259 newborns with no such a sign. In both groups the umbilical cord blood IgG, IgM and IgA concentration (g/L) were quantified by a radial immunodiffusion method. The obtained values were classified into the groups according to 500-grams-birth-weight-ranges. The differences of the mean IgG, IgM and IgA concentrations between the each 500-grams-birth-weight-range subgroup separately in both control and experimental group so as between the same subgroup of the control and experimental group were tested by the means of the Student's t-test. Obtained results did not express the significant differences in the mean IgG, IgM and IgA umbilical cord blood concentrations between the experimental and control group of the newborns.

Birth Weight↗
PubMedDate not supplied

A defective herpes simplex virus vector system for gene delivery into the brain: comparison with alternative gene delivery systems and usefulness for gene therapy.

The delivery of exogenous genes into the brain is becoming an increasingly important strategy for answering questions about the molecular mechanisms of brain function. Answers to these questions may be applied to many of the disorders that affect the brain. For example, a detailed understanding of the mechanisms that modulate long-term changes in neurotransmitter release will almost certainly lead to new approaches to diseases such as the epilepsies, in which neurotransmitter release is altered. Knowledge of the molecular means by which neurotransmitters shape neuronal development and cause neurodegeneration, or how trophic factors regulate neuronal health, will lead to insights into how defects in these pathways cause specific diseases. To answer these questions, we have developed a defective herpes simplex virus (HSV) system for the delivery of exogenous genes into the brain. This system directs precise spatial and temporal expression of recombinant genes in the brain. We discuss its utility in comparison to other methods of gene transfer into the brain for answering basic questions about the molecular basis for neuronal physiology and for gene therapy.

Animals↗
PubMed1997

Guidelines for audiology service delivery in nursing homes. Ad Hoc Committee on Audiology Service Delivery in Home Care and Institutional Settings. American Speech-Language-Hearing Association.

The increasing number of older adults in society as well as changing consumer preference and health care delivery systems have led to more frequent activity of audiologists in the delivery of services in nursing homes. The nursing home setting presents a number of challenges for the audiologist. It is anticipated that this document will provide audiologists with a comprehensive hearing management protocol and facilitate audiologists to confront the numerous challenges of the nursing home setting and provide quality audiology services.

Audiology↗
PubMed1998

Delayed-interval delivery in a quadruplet pregnancy after intrauterine death of a partial molar pregnancy and preterm delivery. A case report.

BACKGROUND: Delayed-interval delivery is infrequent in twin gestation and more rare in triplet and quadruplet gestation. Coexistence of a triploid pregnancy with a normal fetus has not previously been reported to have resulted in survival of the normal fetus. CASE: A 26-year-old woman, gravida 2, para 0-0-1-0, was diagnosed with a quadruplet pregnancy. At 16 1/2 weeks' gestation she developed preeclampsia and severe hyperemesis. Ultrasound was consistent with partial molar pregnancy in quadruplet D. Quadruplet D died in utero, and the preeclampsia and hyperemesis resolved. At 19 5/7 weeks, spontaneous rupture of the membranes and preterm labor occurred, and quadruplet A, stillborn female weighing 260 g, was delivered. With the use of antibiotic therapy, tocolysis and bed rest, the remaining two fetuses were maintained in utero until 32 6/7 weeks' gestation, when quadruplet B, a 1,470-g female, and quadruplet C, a 1,700-g female, were delivered. CONCLUSION: This was the first reported case of surviving fetuses coexisting with a partial molar pregnancy. This case was also complicated by preterm delivery and successful delayed-interval birth in a quadruplet pregnancy.

Adult↗
PubMed2001

Novel site-specific chemical delivery system as a potential mydriatic agent: formation of phenylephrine in the iris-ciliary body from phenylephrone chemical delivery systems.

The objective of this study was to test the three novel ester derivatives of phenylephrone (isovaleryl, phenylacetyl, and pivalyl esters) as potential site-specific chemical delivery systems. The mydriatic effect and ocular distribution/metabolism of these compounds were studied by topical application to the eyes of normal rabbits. It was assumed that a reduction-hydrolysis sequence could produce the active phenylephrine in the iris-ciliary body tissues. All the derivatives showed a more pronounced mydriatic effect than that of phenylephrine, whereas phenylephrone was completely devoid of any mydriatic activity. Phenylacetyl ester was the most potent drug, with short duration of action, and showed maximum activity in the presence of 0.01% benzalkonium chloride without causing any visible irritation to the rabbit eye. Administration of the novel compounds to the eyes of the rabbits showed no traces of phenylephrine in the systemic circulation, contrary to topical administration of phenylephrine. Phenylephrone was detected in different compartments of the eye, whereas phenylephrine was present only in the iris-ciliary body tissues following administration of phenylacetyl ester. The conversion of phenylephrone esters to the active drug, phenylephrine, and thus their subsequent activity was dependent on the physicochemical characteristics of the drugs. The results suggest the potential use of phenylacetyl ester as a potent short-term mydriatic agent without systemic side effects.

Animals↗
PubMed1978

The single-unit delivery system--a safe alternative to home deliveries.

The need has arisen for the development of a health care/delivery system that can allow for a natural and personalized childbirth experience, within the safe confines of a modern obstetric unit. The single-unit delivery system (SUDS) is designed to achieve this objective by: strict prenatal screening of patients into low- and high-risk categories, utilization of a single room for the entire labor process, and close personalized supervision of women in "normal" labor by trained midwives/monitrixes. Physicians supervise the entire unit and are directly responsible for the management of all high-risk and complicated labors. The SUDS concept has been tried in clinical practice and has been proved to be an effective method of providing safe and satisfying obstetric care without compromising modern obstetric standards.

Delivery, Obstetric↗
PubMed2005

Cholesterol-bile salt vesicles as potential delivery vehicles for drug and vaccine delivery.

The aim of this study was to further investigate the interactions between cholesterol (CH) and mixed bile salts (BS) (sodium cholate and sodium deoxycholate) and their suitability for drug and vaccine delivery. Insulin was used as a model protein to assess the ability of CH:BS vesicles to entrap a therapeutically relevant macromolecule. The association of protein (FITC-insulin) with the CH:BS structure was confirmed with fluorescence microscopy, and the overall morphology of the vesicles was examined with atomic force microscopy (AFM). Results demonstrate that the nature of the vesicles formed between CH and BS is dependent not only on the concentration of BS but also on the increasing CH concentration leading to CH crystal formation.

Bile Acids and Salts↗
PubMed2006

A novel in situ forming drug delivery system for controlled parenteral drug delivery.

The objective of this study was to investigate the in vitro drug (diltiazem hydrochloride and buserelin acetate) release from different in situ forming biodegradable drug delivery systems, namely polymer solutions (in situ implants) and in situ microparticle (ISM) systems. The drug release from ISM systems [poly(d,l-lactide) (PLA) or poly(d,l-lactide-co-glycolide) (PLGA)-solution dispersed into an external oil phase] was investigated as a function of the type of solvent and polymer, polymer concentration and internal polymer phase:external oil phase ratio and was compared to the drug release from in situ implant systems and microparticles prepared by conventional methods (solvent evaporation or film grinding). Upon contact with the release medium, the internal polymer phase of the ISM system solidified and formed microparticles. The initial drug release from ISM systems decreased with increasing polymer concentration and decreasing polymer phase:external oil phase ratio. The type of biocompatible solvent also affected the drug release. It decreased in the rank order DMSO>NMP>2-pyrrolidone. In contrast to the release of the low molecular weight diltiazem hydrochloride, the peptide release (buserelin acetate) was strongly dependent on the polymer degradation/erosion. One advantage of the ISM system when compared to in situ implant systems was the significantly reduced burst effect because of the presence of an external oil phase. ISM systems resulted in drug release profiles comparable to the drug release of microparticles prepared by the solvent evaporation method. Therefore, the ISM systems are an attractive alternative to existing complicated microencapsulation methods.

Buserelin↗
PubMed2004

Oral delivery of macromolecules using intestinal patches: applications for insulin delivery.

Oral drug delivery, though attractive compared to injections, cannot be utilized for the administration of peptides and proteins due to poor epithelial permeability and proteolytic degradation within the gastrointestinal tract. A novel method is described that utilizes mucoadhesive intestinal patches to deliver therapeutic doses of insulin into systemic circulation. Intestinal patches localize insulin near the mucosa and protect it from proteolytic degradation. In vitro experiments confirmed the secure adhesion of patches to the intestine and the release of insulin from the patches. In vivo experiments performed via jejunal administration showed that intestinal insulin patches with doses in the range of 1-10 U/kg induced dose-dependent hypoglycemia in normal rats with a maximum drop in blood glucose levels of 75% observed at a dose of 10 U/kg. These studies demonstrate that reduction in blood glucose levels comparable to that induced by subcutaneous injections can be achieved via enteral insulin absorption with doses only 2-10-fold higher than subcutaneous doses.

Administration, Oral↗
PubMed2004

Epithelial-directed drug delivery: influence of formulation and delivery devices.

Technology to deliver drugs reliable throughout the entire respiratory tract has greatly improved in part because of asthma- and infectious disease-related applications. Recent improvements with spiral CT technology applied to detect early lung cancer in high risk populations have also enhanced the prospect of finding locally confined primary lung cancers. In this setting, the need to safely and economically manage the local regional phase of early lung cancer is assuming great strategic importance. At the same time the growing knowledge regarding the molecular and biochemical events driving the progression of lung cancer is allowing the development of targeted drug that may be useful in arresting lung cancer progression. The questions considered in this forum is whether improvements in these areas are sufficiently mature to allow application of local regional drug delivery with targeted drug agents to improve the management of early lung cancer.

Antineoplastic Agents↗
PubMed2002

In vivo evaluation of novel hyaluronan/chitosan microparticulate delivery systems for the nasal delivery of gentamicin in rabbits.

Biodegradable microparticles containing gentamicin were prepared using chitosan hydroglutamate (CH), hyaluronic acid (HA) and a combination of both polymers by a solvent evaporation method. These formulations were administered nasally via an insufflator. Gentamicin was also administered nasally into rabbits as a solution and powder (a physical mixture of gentamicin and lactose), intravenously (IV) and intramuscularly (IM). The resultant serum levels of gentamicin were determined by Fluorescence Polarisation Immunoassay (FPIA). The bioavailability of gentamicin was poor when administered as a nasal solution (1.1%) and dry powder (2.1%) when compared with IV. However, the microparticulate systems composed of CH and HA/CH considerably enhanced the bioavailability of gentamicin (31.4 and 42.9%, respectively,) with HA microparticles inducing a less significant enhancement (23.3%). Previous in vitro dissolution and frog palate studies indicated that these microparticulate formulations were all mucoadhesive and demonstrated prolonged drug release. Such findings were translated into an increase in the bioavailability of gentamicin when compared with a simple nasal solution in vivo. When HA and CH were combined in the HA/CH formulation, the polymers appeared to improve the absorption of incorporated gentamicin synergistically in comparison to the individual polymers, suggesting a promising nasal delivery system.

Adjuvants, Pharmaceutic↗
PubMed2003

Periodontal delivery of ipriflavone: new chitosan/PLGA film delivery system for a lipophilic drug.

The aim of the present work was to design a film dosage form for sustained delivery of ipriflavone into the periodontal pocket. For this purpose, monolayer composite systems made of ipriflavone loaded poly(D,L-lactide-co-glycolide) (PLGA) micromatrices in a chitosan film form, were obtained by emulsification/casting/evaporation technique. Multilayer films, made of three layers of polymers (chitosan/PLGA/chitosan), were also prepared and compared to monolayer films for their "in vitro" characteristics. Morphology and physico-chemical properties of the different systems were evaluated. The influence of pH, ionic strength and enzymatic activity on film degradation, was also investigated. Significant differences in swelling, degradation and drug release were highlighted, depending on film structure and composition. In vitro experiments demonstrated that the composite micromatricial films represent a suitable dosage form to prolong ipriflavone release for 20 days.

Chitin↗
PubMedDate not supplied

A nanoparticle-based model delivery system to guide the rational design of gene delivery to the liver. 2. In vitro and in vivo uptake results.

In Part 1 of our work (1), four nanoparticles were synthesized specifically for the purpose of identifying design constraints to guide next generation gene delivery to the liver. The four nanoparticles are Gal-50 and Gal-140 (galactosylated 50 and 140 nm nanoparticles) and MeO-50 and MeO-140 (methoxy-terminated 50 and 140 nm nanoparticles). All four particles have the same surface charge, and Gal-50 and Gal-140 have the same surface galactose density (ca. 25-30 pmol/cm2). Here, the hepatocyte uptake in vitro and hepatic distribution in vivo of these four nanoparticles is investigated. With freshly isolated hepatocytes, Gal-50 nanoparticles are taken up to a greater extent than are MeO-50, and both 50 nm beads are taken up to a much greater extent than either of the 140 nm nanoparticles. In mice, about 90% of the in vivo dose of Gal-140 nanoparticles is found within the liver 20 min after tail-vein injection. TEM and immunohistochemistry images confirm that Gal-140 nanoparticles are primarily internalized by Kupffer cells, though isolated examples of a few Gal-140 in hepatocytes are also observed. Gal-50 nanoparticles are overwhelmingly found in vesicles throughout the cytoplasm of hepatocytes, with only isolated examples of Kupffer cell uptake 20 min after tail vein injections in mice. Despite similar surface charge and ligand density, 50 nm nanoparticles are primarily found in hepatocytes while 140 nm nanoparticles are primarily observed in Kupffer cells. These results clearly show that slightly anionic, galactose-PEGylated nanoparticles with 25-30 pmol/cm2 galactose should be about 50 nm in diameter to preferentially target hepatocytes while they should be about 140 nm in diameter to selectively target Kupffer cells.

Animals↗
PubMedDate not supplied

Use of designed peptide linkers and recombinant hemoglobin mutants for drug delivery: in vitro release of an angiotensin II analog and kinetic modeling of delivery.

We have designed and tested specific peptide linkers for the glutathione-mediated reductive release of the angiotensin II analog N-acetyl-CGDKVYIHPF attached to recombinant human hemoglobin mutants by a disulfide bond. Inclusion of negatively charged residues decreased the rate of release by as much as 5-fold for the N-terminal linker DCD when compared to that of the control linker CG. Two different surface cysteine mutants in the second domain of the alpha,alpha-chain of recombinant human hemoglobin, D75C and K16C, were examined for their effect on the release of peptide by reduced glutathione. The reaction of the D75C-peptide conjugate with glutathione for release of the peptide is slow, with a second-order rate constant of 2.1 M-1 S-1, allowing the possibility of long term delivery. The rate of peptide release from the K16C vs the D75C mutant was decreased 15-fold. Thus, different peptide release rates can be obtained by changing both peptide linker residues and the surface location of peptide attachment. Kinetic modeling of this release using either measured or literature values for different parameters suggests boundary conditions for application to the in vivo release of peptidomimetics, small molecules, or other drugs bound to the hemoglobin surface.

Angiotensin II↗
PubMed2001

Systemic delivery of cetrorelix to rats by a new aerosol delivery system.

PURPOSE: To study the pulmonary absorption and tolerability of various formulations of the decapeptide cetrorelix acetate in rats by a new aerosol delivery system (ASTA-ADS) for intratracheal application. METHODS: Using the ASTA-ADS, cetrorelix liquid formulations (aqueous solutions for ultrasonic nebulization) were firstly selected and subsequently delivered as nebulized aerosol to orotracheally cannulated rats. The pharmacologic effect (decrease of testosterone serum level) of four cetrorelix formulations was determined in rats by enzyme linked immunosorbant assay, and pharmacokinetic data were determined after measurement of cetrorelix serum level by radioimmunoassay. Histological examination of the lung was performed at the end of the experiments, and in a supplementary experiment the respiratory parameters (resistance and compliance) of rats were monitored by a validated pulmonary monitoring system during the aerosol application of the same formulations. RESULTS: After an exposure time of 5 min, the applied formulations reduced the testosterone concentration in serum to subnormal levels (< or =1 ng/ml) over a period of 24 h. Comparing the plasma concentration after intratracheal aerosolization with data of intravenous administration, the mean calculated bioavailabilities for the four formulations using the corrected dose (delivered--exhaled amount) were between 48.4 +/- 27.0% and 77.4 +/- 44.0%. The histologic examination of the lungs revealed different tolerability of the various tested formulations ranging from locally intolerable to well tolerated. The measurement of the lung function parameters did not reveal any compound or formulation related changes. CONCLUSIONS: Our studies show that cetrorelix can be effectively administered as aerosol and that intratracheal aerosolization via the ASTA-ADS provides results that are well comparable to other application routes, as demonstrated by statistical comparison of the newly obtained data with previous results from intratracheal instillation of cetrorelix solutions in rats.

Administration, Inhalation↗
PubMed1993

Hydrogel-based iontotherapeutic delivery devices for transdermal delivery of peptide/protein drugs.

Hydrogels were synthesized as the drug reservoir matrix for peptide-based pharmaceuticals, and the iontophoretic release and transdermal delivery of three model peptides, insulin, calcitonin, and vasopressin, from these hydrogel-based iontotherapeutic devices were investigated. The swelling behavior of polyacrylamide-type hydrogel as a function of its monomer and cross-linker concentration was studied, and a hydrogel with minimal swelling was synthesized. The release of peptides from the hydrogel matrix was found to follow a Q vs t1/2 relationship under passive diffusion conditions, which shifted to a Q vs t relationship under iontophoresis-facilitated transport. The release flux (dQ/dt) of peptides was observed to decline when the electric current was turned off and was resumed when the current was turned on, thus allowing for modulation of drug release by varying the application parameters of iontophoresis-facilitated transport. The permeability coefficients for these peptides across the hairless rat skin were evaluated using the hydrogel formulations prepared from polyacrylamide, p-HEMA, and carbopol. A rank order of vasopressin > calcitonin > insulin was obtained in accordance with the order of molecular size.

Acrylic Resins↗
PubMed2000

Kinetics of a model nucleoside (guanosine) release from biodegradable poly(DL-lactide-co-glycolide) microspheres: a delivery system for long-term intraocular delivery.

The objective of this study was to prepare poly(DL-lactide-co-glycolide) (PLGA) microspheres containing guanosine as a model drug for intraocular administration. Microspheres were prepared by solvent evaporation technique using o/w emulsion system. The influence of composition and molecular weight of PLGA, drug loading efficiency, microsphere size, and in vitro and in vivo release rates were determined. Differential scanning calorimetry (DSC) and FTIR studies were conducted to examine the guanosine-polymer interaction. In vitro release studies indicated that the permeant release from microspheres exhibits an initial burst followed by slow first-order kinetics. Ascending molecular weights of the polymers generated progressively slower release rates. Three different sizes of microspheres were prepared. The release continued for 7 days with a maximum of 70% of the content released within that time period. DSC and FTIR studies showed no polymer-guanosine interaction. A novel microdialysis technique was used to examine the initial release kinetics from microspheres in isolated vitreous humor. This technique was also employed to observe in vivo intravitreal release in albino rabbits. A good correlation exists between in vitro and in vivo release rates from both 75 and 140 kDa PLGA microspheres. Guanosine-loaded microspheres could be prepared for once-a-week intravitreal injection with minimum required concentration maintained throughout the dosing interval. Because the structural and solubility characteristics of guanosine are similar to those of acyclovir and ganciclovir (two acycloguanosine analogues effective against herpes simplex virus [HSV-1] and cytomegalovirus [CMV], respectively), similar biodegradable polymer-based microsphere technology can be employed for the long-term intraocular delivery of these two drugs.

Animals↗
PubMed1999

Transdermal testosterone delivery: comparison between scrotal and nonscrotal delivery systems.

The purpose of this investigation was to study the bioequivalence of two testosterone transdermal delivery systems (T-TDSs). Testoderm, designed to deliver testosterone through scrotal skin, and Androderm, designed for nonscrotal permeation. In vitro permeation and release kinetics as well as in vivo pharmacokinetics in the castrated Yucatan miniature swine (minipigs) model of both T-TDSs were studied side by side under the same experimental conditions. In vitro skin permeation kinetics studies demonstrated that testosterone permeates through minipig dorsal skin at zero-order kinetics from both T-TDSs. The nonscrotal T-TDS, however, has a permeation rate which is approximately 13 times higher than that for the scrotal T-TDS. The release of testosterone from the nonscrotal T-TDS showed a biphasic release profile between cumulative amount released and time, whereas a monophasic release profile between cumulative amount released and square root of time was observed for the scrotal T-TDS. Pharmacokinetic analysis of plasma testosterone profiles in minipigs indicated a significant difference (p < 0.001) in daily dose of testosterone delivered (1.20 versus 4.83 mg/day), maximum concentration (Cmax) (54.2 versus 218.0 ng/dl), and area under concentration-time curve (AUC0-28)[665 versus 3208 (ng/dl) x hr] between these T-TDSs. However, there is no difference in time to reach Cmax mean residence time, and daily-delivered-dose-normalized Cmax and AUC0-28. The difference in pharmacokinetic profiles resulted from the difference in daily doses delivered, which could be attributed remarkably to the difference in permeation rate (approximately 13-fold) between the nonscrotal and scrotal T-TDSs.

Administration, Cutaneous↗