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Biomedical subjects

H Viernstein

Publications and source records attributed to H Viernstein.

17 recordsLinked to original sources
PubMed2006

Lectin binding studies on C-28/I2 and T/C-28a2 chondrocytes provide a basis for new tissue engineering and drug delivery perspectives in cartilage research.

The present study was performed to evaluate the applicability of plant lectins as mediators of bioadhesion in cartilage research using human chondrocyte cell lines C-28/I2 and T/C-28a2. The bioadhesive properties of fluorescein-labelled lectins with different carbohydrate specificities were investigated by flow cytometry. Specificity of the lectin-cell interactions was ascertained by competitive inhibition using complementary carbohydrates. As compared to that of other lectins, the interaction between wheat germ agglutinin (WGA) and chondrocytic cells was characterised by remarkable cytoadhesion, adequate binding strength and a high degree of specificity for N-acetyl-glucosamine as contained in hyaluronan chains. We therefore suggest WGA to be a promising candidate for mediating bioadhesion to low-adhesive scaffolds in cartilage tissue engineering. Moreover, the WGA-association rate of C-28/I2 and T/C-28a2 cells was dependent on temperature indicating cellular uptake of membrane-bound WGA. Intracellular enrichment was confirmed by confocal microscopy. Equilibration of intracellular pH gradients with monensin resulted in the reversal of quenching effects indicating accumulation of WGA within acid compartments of chondrocytic cells. Thus, WGA might be internalised into chondrocytes together with hyaluronan via the CD44 receptor-mediated endocytosis pathway and accumulated within lysosomes. This physiological process could represent a feasible pathway to target WGA-functionalised drug delivery devices into chondrocytes.

Acetylglucosamine↗
PubMed2006

Deficiences in phenotype expression and function of dentritic cells from patients with early breast cancer.

PURPOSE: Monocytes derived from patients with early breast cancer (EBC) have shown functional deficiencies. These functional deficiencies are characterized by changes in phenotype and morphology. We have expanded these investigations to dendritic cells generated from monocytes from patients with early breast cancer. - PATIENTS AND METHODS: Peripheral blood from 36 patients with EBC and from 26 healthy age-matched women was drawn and prepared for ex vivo generation of dendritic cells (DC) by incubation with granulocyte/macrophage-colony stimulating factor (GM-CSF) and interleukin 4 (IL4). The phenotype of DC was examined by flow-cytometry. T cell - proliferation was induced with tetanus toxoid pulsed autologous dendritic cell. - RESULTS: Dendritic cells generated from monocytes from EBC-patients showed a significantly lower expression of the phenotype-associated antigens CD1a, CD83, CD80, CD86 and CD54 than the dendritic cells from healthy controls. T cell - proliferation in response to TT-pulsed autologous dendritic cells was significantly decreased when induced with dendritic cells from patients with early breast cancer, when compared to healthy controls. Morphologically, only dendritic cells from healthy women possessed prominent dendrites indicating maturity. - CONCLUSIONS: These findings indicate that dendritic cells generated from monocytes from patients with early breast cancer express an immature phenotype, exhibit immature morphology and show functional deficits when compared to the cells derived from healthy age-matched controls. Whether these findings offer a potential target for therapeutic interventions remains to be elucidated.

Adult↗
PubMed2004

Beauveria brongniartii subjected to spray-drying in a composite carrier matrix system.

The negative aspects of chemical pesticides are of growing concern to the public. Thus, there is a strong effort to exploit environmentally friendly possibilities for pest management. One strategy is the application of biocontrol agents such as the fungus Beauveria brongniartii. In this context, the central objective of the research presently described is to investigate spray drying as a preservation method for fungal conidia to obtain a practical formulation for spray application. An aqueous binary mixture composed of skim milk (SM) and polyvinylpyrrolidone (PVP K90) was examined as encapsulation matrix. The influence of different inlet/outlet temperature adjustments, the composition of the carrier system and the conidia concentration were examined with respect to their influence on spore viability. Results indicate that air outlet temperatures up to 53 +/- 2 degrees C resulted in a slight reduction of conidial viability (approximately 3%). Microencapsulated conidia have been subjected to storage tests with and without the addition of silica gel capsules at various temperatures. Results show that survival is inversely related to storage temperatures and residual moisture levels of the spray dried powders. The highest survival rates were observed at moisture contents of 3% and a temperature of 10 degrees C. Moreover, production characteristics like entrapment efficacy, shape and size were investigated. Furthermore, the composition of the carrier matrix was optimised to result in production yields of 25%. Results show that spray drying is a useful, economic encapsulation technology for aerial conidia of Beauveria brongniartii resulting in highly concentrated, spray dried powders of 92% viability.

Animals↗
PubMed2003

Optimization of a formulation containing viable lactic acid bacteria.

In the present study, gastric juice resistant tablet formulations of lactic acid bacteria (LAB) were developed, using hydroxypropylmethylcellulose acetate succinate (HPMCAS) as well as alginates, apple pectin and Metolose as matrix forming components. To optimize the formulation-using survival rate in acid medium, and disintegration time in intestinal fluid as test parameters-tablets were modified with respect to LAB content, amount of applied excipients per tablet, and compaction forces. A decrease of viable cells of not more than one log unit after 2h of incubation in acid medium was desired, as well as a disintegration time of 1h in phosphate buffer pH 6.8. It was found that the amount of HPMCAS in the tablet correlates with gastric juice resistance. As HPMCAS also leads to a decrease of disintegration time in intestinal fluid, slight amounts of this excipient were preferred. The best protective qualities against artificial gastric juice were observed when tablets were prepared from compaction mixtures of LAB, HPMCAS and sodium alginate.

Colony Count, Microbial↗
PubMed2003

Action of pyrethrum-based formulations against grain weevils.

Pyrethrum extract, containing six insecticidal esters, has a long history of successful application in the control of stored products. Its low environmental hazard makes it an ideal pesticide for outdoor pre-harvest treatment. However the disadvantage of its low light stability then becomes apparent. This drawback can be overcome by the complexation of pyrethrum extract with gamma-cyclodextrin. Primary object of the conducted studies was to investigate the effect of complexation upon the insecticidal action against the grain weevil, an important storage pest in temperate climates. To slow down the quick metabolism of pyrethrum by the insects' microsomal system synergistic substances are added. Additional to the already well-known piperonyl butoxide two natural synergists, sesamol and tocopherol acetate, were combined with pyrethrum extract to investigate their synergistic activity. A complex of pyrethrum with gamma-cyclodextrin, with piperonyl butoxide as synergist, has a slightly enhanced action compared to a commercial product, which contained pyrethrum in its free form. Sesamol and tocopherol acetate also display a synergistic action, but to a much smaller degree, even if applied in larger amounts. The optimal concentration of pyrethrum was found to be 0.3% combined with 3% piperonyl butoxide.

Animals↗
PubMed2002

Clustering of Saccharomyces boulardii strains within the species S. cerevisiae using molecular typing techniques.

AIMS: This study was undertaken to characterize and differentiate therapeutically relevant Saccharomyces yeasts. Among the isolates were so-called Saccharomyces boulardii strains, which are considered as probiotic agents, but whose taxonomic assignment is controversial. Moreover, the discriminative power of the applied molecular typing techniques should be evaluated. METHODS AND RESULTS: Genotyping was performed using species-specific polymerase chain reaction (PCR), randomly amplified polymorphic DNA-PCR, restriction fragment length polymorphism analysis of rDNA spacer regions and pulsed-field gel electrophoresis. Species-specific PCR assigned all of the product isolates to the species S. cerevisiae. By combining the other techniques, all isolates could be discriminated. Moreover, it could be demonstrated that probiotic S. boulardii strains form a separate cluster located within the species. CONCLUSIONS: With the exception of species-specific PCR, all of the applied methodologies were suitable for subspecies typing and indicated a close relationship between the probiotic strains. SIGNIFICANCE AND IMPACT OF THE STUDY: The methods applied in this study are considered powerful tools for quality control of therapeutically relevant yeasts. It is of crucial importance, especially regarding S. boulardii yeasts, to verify the identity of the correct strain, since the beneficial properties are considered to be strain-specific.

DNA, Fungal↗
PubMed2001

Utilization of prebiotic carbohydrates by yeasts of therapeutic relevance.

AIMS: To investigate 17 strains of therapeutically relevant strains of Saccharomyces cerevisiae (including 10 strains of so-called S. boulardii) isolated from various pharmaceutical products, feed supplements and brewer's yeast for their capability of utilizing selected carbohydrates of prebiotic importance. METHODS AND RESULTS: Automated turbidimetric measurements and conventional test combinations were used to examine the basic sugar assimilation profiles of the test strains. It was shown that none of the so-called S. boulardii strains utilized galactose and palatinose. Among the prebiotic substrates, the yeasts indicated a pronounced preference for metabolizing the fructo-oligosaccharides. CONCLUSION: Yeast strains of therapeutic relevance can be successfully combined with certain prebiotics in symbiotic formulations. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this study may serve as a basis for the development of new pharmaceutical preparations for medical therapy and a better understanding of intestinal micro-ecology.

Carbohydrate Metabolism↗
PubMed2000

Predicting the free energies of complexation between cyclodextrins and guest molecules: linear versus nonlinear models.

PURPOSE: In the present paper, linear and nonlinear models for complexation of alpha- beta- and gamma-cyclodextrin with guest molecules are developed, with the aim of free energy prediction and interpretation of the association process. METHODS: Linear and nonlinear regression is used to correlate experimental free energies of complexation with calculated molecular descriptors. Molecular modeling supports the interpretation of the results. RESULTS: Highly predictive models are obtained, although the structural variability of the compounds used for their deduction is large, reaching from synthetic heterocycles to steroids and prostaglandins. CONCLUSIONS: The scaled regression coefficients give insight to the complexation mechanisms, which appear to be different for the three types of cyclodextrins.

Cyclodextrins↗
PubMed1999

Toxicity of a particulate formulation for the intraperitoneal application of mitoxantrone.

Mitoxantrone (MXN) has demonstrated therapeutic efficacy in the intraperitoneal treatment of malignancies. However, severe local toxicity is dose limiting. Therefore, a particulate formulation of MXN, the drug incorporated in albumin microspheres, was evaluated concerning tolerability. Survival rates as well as alterations in body weight, food intake, water intake, urine volume, urine specific gravity, urine protein content, and complete blood count were observed following single or multiple intraperitoneal injections of MXN solution, dispersions containing MXN-loaded microspheres or unloaded microspheres, and the injection vehicle to female and male Sprague-Dawley rats. Applied MXN dosage was equivalent to 30 mg/m2 body surface area. Unloaded microspheres were well tolerated without signs of toxicity. Application of MXN solution or MXN-loaded microspheres resulted in similar survival rates (56% 9 weeks after single injection) and in a comparable bone marrow toxicity (mainly leucopenia). Body weight, food and water intake as well as urine volume were decreased following application of MXN solution, whereas a progressive gain in weight and no remarkable alterations in nutrition and urine excretion were noted after administration of MXN-loaded and unloaded microspheres, or of the injection vehicle. In conclusion, intraperitoneal injection of MXN incorporated in albumin microspheres exhibits in part less toxicity than conventional treatment.

Animals↗
PubMed1999

Evaluation of mitoxantrone-loaded albumin microspheres following intraperitoneal administration to rats.

Mitoxantrone has demonstrated therapeutic efficacy in the regional treatment of intraperitoneal malignancies. However, severe local toxicity was dose limiting. Consequently, a new injectable sustained delivery formulation of mitoxantrone has been developed: the drug was incorporated (8.2 w/w%) in highly hydrophilic albumin microspheres. In vitro drug release profile was modified by matrix crosslinking extent. The extractable amount of residual crosslinking agent (glutaraldehyde) in the microspheres was lower than 6 ppm. Mitoxantrone concentration in peritoneal fluid and plasma was determined up to 72 h after intraperitoneal administration of 30, 60 and 120 mg mitoxantrone per m2 body surface area as solution and in the form of a dispersion containing mitoxantrone-loaded microspheres to rats. Data analysis revealed sustained release of mitoxantrone from microspheres into peritoneal fluid in all dosage groups. The initial high drug levels in peritoneal fluid and plasma observed after application of mitoxantrone in the solution form were prevented by administration of the drug incorporated in microspheres. However, tumoricidal drug levels in peritoneal fluid were maintained over a comparable time span. In addition, preliminary toxicity data suggest a superior local tolerability of mitoxantrone-loaded microspheres. The dose of intraperitoneally administered mitoxantrone might be increased from 30 to 60 mg per m2 body surface area using the slow release formulation. In conclusion, the described microsphere drug delivery system for mitoxantrone might overcome dose-limiting drug toxicity.

Albumins↗
PubMed1999

[Dosage forms of phytogenic drugs].

Herbal drug formulation is a challenge in pharmaceutical technology due to the complex physicochemical properties of these multicomponent materials. Potential instabilities of the pharmacologically active and coactive substances as well as incompatibilities and interactions of the extracted compounds and excipients have to be considered. Microbial contamination of the applied plant material might limit the shelf life of the products. Using state of the art methods in formulation stable preparations are obtained; additionally compliance of drugs might be enhanced due to simplified application or better sensorial quality. Nowadays, besides traditional pharmacopoeial aqueous, ethanolic, or (partially) dried extracts fluid, semisolid, or solid dosage forms of these extracts are in use, for example syrups, juices, drops, liniments, gels, ointments, creams, suppositories, tablets, coated tablets (dragees) as well as soft and hard gelatine capsules.

Dosage Forms↗
PubMed1993

Preparation and central action of propofol/hydroxypropyl-beta-cyclodextrin complexes in rabbits.

Inclusion complexes of propofol (CAS 2078-54-8) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) were examined in aqueous solution and in the solid state by phase solubility technique, IR-spectroscopy and differential scanning calorimetry. Solid complexes obtained by kneading method were dissolved in artificial plasma leading to a colloidal solution which was suitable for intravenous administration. In the in vivo studies propofol (15 mg/kg) was given intravenously to rabbits in equimolar doses as cyclodextrin complexes and as Diprivan. The central action of the drug was verified by recording the bioelectrical activity of the precentral cortex. The statistical evaluation of the results do not indicate differences in onset, duration and maximum of action between the two dosage forms.

Animals↗
PubMed1992

Similar central actions of intravenous methohexitone suspension and solution in the rabbit.

The central actions of solutions of methohexitone sodium and suspensions of methohexitone given intravenously in equimolar doses have been compared. The administrations induced identical anaesthesia. Because, in general, drugs acting upon the central nervous system are poorly soluble in water, this finding should be useful for routine pharmacological investigations as it avoids the use of organic solvents which may themselves affect the central nervous system.

Anesthetics↗
PubMed1990

Pharmacological actions of central nervous system depressants given intravenously as suspensions.

Three central nervous system (CNS) depressants, methohexital (sodium), midazolam (maleate), and flunitrazepam, were given intravenously to rabbits in equimolar doses as suspensions and solutions. The mean diameters of the particles in the suspensions were 770, 840, and 460 nm, respectively. The CNS actions were verified by recording the bioelectrical activity of the precentral cortex. The suspensions were tolerated well. There were no differences in onset, duration, and maximal intensity of action between suspension and solution of each drug. The results of this study should facilitate pharmacological studies of drugs acting on the CNS that are insoluble in water.

Animals↗
PubMed1990

[Biological availability of different oral cimetidine preparations in the dog].

Bioavailability of Different Oral Dosage Forms of Cimetidine in Dogs. The bioavailability of cimetidine (200 mg) after oral administration to awake dogs was increased significantly by using tablets containing alginate. In addition the timespan was prolonged during which therapeutic plasma concentrations were maintained. Release and absorption of cimetidine were retarded from tablets containing methacrylic acid-copolymers, but the bioavailability was decreased from this dosage form and therapeutic plasma concentrations were not reached.

Acrylates↗
PubMedDate not supplied

Characterization of microcapsules: recommended methods based on round-robin testing.

Alginate beads, as well as microcapsules based on alginate, cellulose sulphate and polymethylene-co-guanidine, were produced at diameters of 0.4, 1.0 and 1.5 mm. These standard materials were tested, by independent laboratories, in regards to water activity, bead or capsule size, mechanical resistance and transport behaviour. The water activity and mechanical resistance were observed to increase with bead and capsule size. Transport properties (ingress) were assessed using a variety of low molar mass and macromolecular probes. It was observed that the penetration of Vitamin B12 increased with bead diameter, as did dextran penetration. However, for the membrane-containing microcapsules, larger membrane thickness, observed for the larger capsules, retarded ingress. The authors, who are part of a European working group, recommend that permeability be assessed either using a large range of probes or a broad molar mass standard, with measurements at one or two molar masses insufficient to simulate the behaviour in application. Mechanical compression is seen as a good means to estimate elasticity and rupture of beads and capsules, with the sensitivity of the force transducer, which can vary from microN to tens of N, required to be tuned to the anticipated bead or capsule strength. Overall, with the exception of the mechanical properties, the precision in the inter-laboratory testing was good. Furthermore, the various methods of assessing transport properties agreed, in ranking, for the beads and capsules characterized, with gels having smaller radii being less permeable. For microcapsules, the permeation across the membrane dominates the ingress, and thicker membranes have lower permeability.

Alginates↗