Biomedical subjects

A Ludwig

Publications and source records attributed to A Ludwig.

At least 37 records · Page 2Linked to original sources

PubMed2003

Safety-assessment of 3-methoxyquercetin as an antirhinoviral compound for nasal application: effect on ciliary beat frequency.

It has been shown that 5,7,3',4'-tetrahydroxy-3-O-methylflavone (3-MQ) exhibits antipicornaviral activity. In order to explore the potential of 3-MQ as an antirhinoviral compound for nasal application, the effect of 3-MQ on the ciliary beat frequency (CBF) of human nasal epithelial cells was studied in vitro in the absence or presence of solubility/absorption enhancers (hydroxypropyl-beta-cyclodextrin (HP-beta-CD) or polysorbate 80). Nasal epithelial cells were obtained by protease digestion of surgical specimens of human nasal polyps, and used at confluency. The effect of 3-MQ (2, 10, and 20 microg/ml), HP-beta-CD (1, 3, and 10% (w/v)), polysorbate 80 (0.1, 0.3, and 1% (w/v)), and of the combination of 3-MQ with 3% HP-beta-CD or 1% polysorbate 80, on the CBF was determined by computerized microscope photometry 15 min after incubation with the test compounds; recovery was determined 35 min after rinsing. HP-beta-CD at 1 and 3% did not affect CBF; a reversible decrease (by 37%) was observed at 10%. Polysorbate 80 caused a reversible cilio-inhibitory effect of 40, 53, and 49% at 0.1, 0.3, and 1%, respectively. At 2 and 10 microg/ml, 3-MQ showed a reversible cilio-stimulatory effect of 18 and 14%, respectively. Combined with 3% HP-beta-CD, the reversible cilio-stimulatory effect of 2 microg/ml 3-MQ was preserved, while 10 and 20 microg/ml 3-MQ did not affect the CBF. The combination of polysorbate 80 (1%) and 3-MQ decreased the CBF, which could be attributed to the presence of polysorbate 80. In conclusion, no ciliotoxic effect could be observed for 3-MQ (up to 20 microg/ml) in the absence or presence of HP-beta-CD (3%). The potential of this combination as an antirhinoviral formulation for nasal application will be further explored.

Administration, Intranasal↗

PubMed2003

Characterization and in vivo evaluation of ocular bioadhesive minitablets compressed at different forces.

The influence of the compression force on the physical properties, the in vitro release and the in vivo behavior of ocular minitablets is evaluated in the present study. The bioerodible minitablets (Ø 2 mm, 6 mg) were produced at different compression forces. The crushing strength, friability, water uptake, hydration and swelling of the minitablets both in vitro as well as in vivo after application in the cul-de-sac were evaluated. The friability remained below 1% only for the minitablets made at 0.500 and 0.750 kN. The crushing strength measured was 3.53+/-0.98, 12.34+/-1.69 and 18.64+/-2.37 N for minitablets made at 0.250, 0.500 and 0.750 kN, respectively. The full hydration time equalled 20 and 30 min for minitablets compressed at 0.250 kN and 0.500-0.750 kN, respectively. Increasing the compression force resulted in a decreased swelling capacity. The in vivo release was evaluated in healthy volunteers using a non-invasive method to measure the apparent sodium fluorescein concentration in the tearfilm-cornea compartment as a function of time. The longest residence time of the fluorescent tracer at the administration site was obtained by the minitablets compressed at 0.750 kN. The in vitro release was evaluated with three different dissolution methods: the reciprocating cylinder method, vials in an oscillatory shaking bath and a static method with vials. The best correlation with the in vivo behavior of the matrix minitablets was obtained with the shaking bath method.

Adhesives↗

PubMed2003

Rheological study on mucoadhesivity of some nasal powder formulations.

Various powder mixtures were used to administer insulin via the nasal route: a co-spray dried mixture of Amioca starch and Carbopol 974 P (1/3), drum dried waxy maize starch and Carbopol 974 P (9/1), maltodextrin DE38/Carbopol 974 P (9/1) and pure drum dried waxy maize starch. Oscillatory rheology is performed to study and compare the viscosity, elasticity and mucoadhesivity of these powder formulations. There was no rheological synergism detectable with the co-spray dried mixture of Amioca starch and Carbopol 974 P (1/3), drum dried waxy maize starch and Carbopol 974 P (9/1) and maltodextrin DE38/Carbopol 974 P (9/1). Interaction due to entanglements was seen with drum dried waxy maize starch (100%). The differences in nasal bioavailability between the different carriers could be explained by differences in G' (storage modulus, elasticity) and G" (loss modulus, viscosity) values. The formulation giving the highest bioavailability, provided also the highest G' and G" values.

Adhesives↗

PubMed2003

Nonconcordant evolutionary history of maternal and paternal lineages in Adriatic sturgeon.

Although analyses of intraspecific variability are an important prerequisite for species identification assays, only a few studies have focused on population genetics and historical biogeography of sturgeon species. Here we present the first study on genetic variability of the last remaining Adriatic sturgeon, Acipenser naccarii, derived from mitochondrial and nuclear DNA. Our mitochondrial DNA analyses arranged individuals into three distinguished mitochondrial DNA haplogroups (Po1, Po2 and Buna). Two haplogroups (Po1 and Buna) were correlated to geographical distribution, whereas the third (Po2) was not. It was, however, very closely related to one lineage of its Ponto-Caspian sister species, A. gueldenstaedtii. The distribution of nuclear markers (microsatellites and amplified fragment length polymorphism) was strongly correlated to geographical distribution. An assignment test based on nuclear data placed no specimen of A. naccarii to A. gueldenstaedtii and vice versa. Therefore, the presence of gueldenstaedtii-like haplotypes within the Po population is either the result of a postglacial introgression or an ancestral polymorphism and does not indicate a hybrid population. The most valuable tool for forensic species identification purposes is one diagnostic deletion separating all A. naccarii from A. gueldenstaedtii. As both A. naccarii populations are genetically differentiated, stocking of sturgeon from the Po River in Italy into waters of the Buna River would jeopardize the genetic differences between both populations and should thus be avoided.

Animals↗

PubMed2002

Biocompatible stabilizers in the preparation of PLGA nanoparticles: a factorial design study.

Poly(lactic-co-glycolic-acid) nanoparticles are often produced using the w/o/w emulsification solvent evaporation method. In most cases poly(vinyl alcohol) (PVA) is used as stabilizer of the emulsion. The goal of this study was to compare a series of polymers to PVA in a 2(2) full factorial design study. The influence of the concentration of PVA and the polymers tested on particle size and zeta potential value was evaluated before and after freeze-drying of the prepared particles. Nanoparticles were obtained with most polymers when they were used in combination with PVA. Leaving PVA out of the formulation, however, increased the size of the particles over 1 microm. Two exceptions are poloxamer and carbopol, which can be considered as valuable alternatives to PVA. Zeta potential values were usually slightly negative, the most extreme zeta potential values were measured when poloxamer and carbopol were employed. The use of gelatin type A made it possible to achieve positive values. The original 2(2) full factorial design study was further expanded to a central composite design for poloxamer and carbopol, in order to fit the measured data to a quadratic model and to calculate response surfaces.

Acrylic Resins↗

PubMed2002

[Anaphylactic shock following intravenous hydrocortisone succinate administration].

Glucocorticoids are frequently used in clinical anaesthesiology and intensive care because of their antiallergic, antiinflammatory and antioedematous properties and anaphylactic reactions are rare. We report on a 62-year-old asthmatic patient with evidence of aspirin sensitivity. We administered 100 mg of hydrocortisone-21-hemisuccinate (Pharmacia & Upjohn, Erlangen, Germany) dissolved in 100 ml 0.9% sodium chloride solution for perioperative corticoid substitution. The patient immediately developed severe bronchospasm and anaphylactic shock requiring intubation and mechanical ventilation. He received adrenaline, isoflurane, ketamine and inhalational fenoterol. He then developed atrioventricular block type III for which we transcutaneously paced the patient. Subsequently he was tested via skin prick tests, intracutaneous tests and i.v.-challenges resulting in the patient having positive reactions to hydrocortisone-21-hemisuccinate. Thus when allergic-like reactions result from glucocorticoid therapy one should consider corticoid allergy as a differential diagnosis.

Anaphylaxis↗

PubMed2002

[Evaluation of B-scan ultrasound, 3-D ultrasound, roentgen diagnosis and sinus endoscopy in follow-up assessment of the maxillary sinus after sinus floor elevation].

PROBLEM: The aim of this study was to determine which technique--B-scan sonography, 3D sonography, X-ray, or endoscopy--is the most effective for diagnosis in changes of the maxillary sinus after sinus lift and simultaneous augmentation. MATERIAL AND METHODS: In 33 patients the maxillary sinus was examined before sinus lift, 1 week and 6 months postoperatively with a 7.5-MHz linear scanner and 3D sonography. At the same time, the sonographic results were compared with the X-ray as well as the endoscopic results. Endoscopy of the maxillary sinus was only applied during the sinus lift operation and the abutment operation after 6 months. RESULTS: A total of 56 operations of sinus lift and simultaneous augmentation with autogenous bone were carried out. Preoperatively, there where no pathological findings detectable in the maxillary sinus. One week postoperatively, the X-rays as well as the sonographic images revealed thickening of the mucosa in 40 maxillary sinuses. After the healing period of 6 months, polyposa was still detected in three cases sonographically, in the radiographic follow-up as well as endoscopically. The sonographic 3D imaging of the maxillary sinus improved the spatial visualization of postoperative changes in the maxillary sinus and the reliability of the diagnosis. CONCLUSION: Due to the lack of radiation, the cost effectiveness, and its reproducibility, sonography is suitable as a primary screening technique in recall. In cases of normal sonographic findings but clinical symptoms, CT, MRT, and endoscopy should be performed to exclude pathological processes of the posterior maxillary sinus.

Alveolar Ridge Augmentation↗

PubMed2002

Long-term follow-up after first acute episode of sigmoid diverticulitis: is surgery mandatory?: a prospective study of 118 patients.

PURPOSE: This study was designed to evaluate the long-term natural history of sigmoid diverticulitis in patients treated nonoperatively after a first acute episode and to assess the role of elective colectomy. METHODS: Between 1986 and 1991, 144 patients were admitted for acute diverticulitis diagnosed by abdominal computed tomography and had a successful nonoperative treatment. Remote complications (persisting or recurring diverticulitis) were also diagnosed by computed tomography. Patients had a poor outcome if they had one of these complications. Diverticulitis was graded mild or severe on computed tomography according to Ambrosetti's criteria. We determined statistically whether young age (< or =50 years old) and severe diverticulitis were risk factors for a poor outcome. RESULTS: One hundred eighteen patients with a contributive computed tomographic scan at admission were followed up. Median age was 63 (range, 23-93) years, with a median follow-up of 9.5 (range, 0.2-13.8) years. Eighty patients had no complications, and 38 had remote complications. The incidence of remote complications was the highest (54 percent at 5 years) for young patients with severe diverticulitis on computed tomography and the lowest (19 percent at 5 years) for older patients with mild disease. Young age and severe diverticulitis taken separately were both statistically significant factors of poor outcome (P = 0.007 and P = 0.003, respectively), although age was no longer significant after stratification for disease severity on computed tomography (P = 0.07). Twenty-four patients died. The cause of death was unrelated to diverticulitis in 21 cases and unknown in the remaining 3. CONCLUSIONS: We propose that after a first acute episode of diverticulitis treated nonoperatively, elective colectomy should be offered to young patients (< or =50 years old) with severe diverticulitis on computed tomography.

Adult↗

PubMed2002

Development of a rheometric technique to measure the mucoadhesive capacity of a dry powder formulation.

In the present study, the use of an in vitro technique applying oscillatory shear rheology to determine the interaction between a dry polymer powder and mucin is investigated. The polymers examined are Carbopol 974P, Noveon AA1 and a polymer mixture containing Carbopol 974P and Drum Dried Waxy Maize Starch. The degree of interaction is assessed by analysing the variation of the elastic and viscous modulus as a function of oscillation stress. Both moduli are used to calculate a mucoadhesive index at a selected single stress/frequency combination. The contribution of physical entanglements and secondary bond formation to the interaction can be derived from the mathematical analysis of the relation between the moduli and the oscillation frequency. When considering the stress sweep data, the interaction between mucin and the various polymers investigated seems very similar. This similarity is also observed when calculating the mucoadhesive indexes. On the contrary, the mathematical analysis of the frequency sweep data clearly indicates that the secondary bond formation between the polymer powder particles and mucin can be obtained only in the case of Carbopol 974 P.

Acrylic Resins↗

PubMed2002

In vitro assessment of the interaction mechanisms between mucin and a cationic cellulosic derivative by rheological methods using an experimental design.

An oscillatory rheological method is used for the determination of the mucoadhesive properties of a cationic cellulosic derivative (JR-30M) proposed for ocular dosage forms and dry eye viscous solutions. An experimental design was set up to study the influence of the concentrations of the polymer and mucin on mucoadhesion. From the rheological data it can be deduced that the interactions between mucin and JR-30M are mainly based on physical entanglements and less on ionic interactions.

Adhesives↗

PubMed2001

Evaluation of a mucoadhesive tablet for ocular use.

The present study investigates the use of a polymer mixture containing Carbopol 974P and drum dried waxy maize starch to obtain prolonged drug release to the anterior eye segment. Two dosage forms with this composition are compared: a hydrated polymer dispersion and a minitablet. A model fluorescent tracer is used to study the ocular release and diffusion from the two dosage forms in humans. To evaluate the prolongation in the cornea/tearfilm compartment, the Apparent Fluorescein TurnOver (%/min) is calculated. The parameters Cmax, tmax, and C9h are used to characterize the pharmacokinetics of Na-fluorescein in the anterior chamber. Furthermore, the swelling behavior of the minitablet is evaluated macroscopically, while the degree of interaction with mucin is characterized by rheological measurements. Calculation of an acceptability score and a slug irritation potential is performed to evaluate user acceptability. In contrast to the hydrated dispersion, the minitablet significantly decreases the Apparent Fluorescein TurnOver (%/min) (P<0.05) and increases the apparent fluorescence in the anterior chamber 9 h after application of the preparation. Rheological data demonstrate the presence of elastic interactions between the polymer and mucin. The dry core of the minitablet becomes fully hydrated after approximately 2 h and is subsequently transformed into a highly concentrated gel. The acceptability of the minitablet is comparable to that of the polymer dispersion. Prolonging the release of Na-fluorescein to the anterior eye segment is only feasible with the dry preparation.

Acrylates↗

PubMed2001

Structural and functional characterization of human NAD kinase.

NADP is essential for biosynthetic pathways, energy, and signal transduction. Its synthesis is catalyzed by NAD kinase. Very little is known about the structure, function, and regulation of this enzyme from multicellular organisms. We identified a human NAD kinase cDNA and the corresponding gene using available database information. A cDNA was amplified from a human fibroblast cDNA library and functionally overexpressed in Escherichia coli. The obtained cDNA, slightly different from that deposited in the database, encodes a protein of 49 kDa. The gene is expressed in most human tissues, but not in skeletal muscle. Human NAD kinase differs considerably from that of prokaryotes by subunit molecular mass (49 kDa vs 30-35 kDa). The catalytically active homotetramer is highly selective for its substrates, NAD and ATP. It did not phosphorylate the nicotinic acid derivative of NAD (NAAD) suggesting that the potent calcium-mobilizing pyridine nucleotide NAADP is synthesized by an alternative route.

Animals↗

PubMed2001

Ribozyme cleavage of telomerase mRNA sensitizes breast epithelial cells to inhibitors of topoisomerase.

Telomerase activity is necessary and sufficient for immortality in many cells and hence represents a prime target for antitumor strategies. Here, we show that a hammerhead ribozyme cleaves human telomerase (hTERT) mRNA in vitro. Stable transfection in clones of the human breast tumor line MCF-7 and the immortal breast cell line HBL-100 results in expression of the ribozyme, diminishes the abundance of hTERT mRNA, and inhibits telomerase activity. This led to shortened telomeres, inhibition of net growth, and induction of apoptosis. In HBL-100 mass cultures infected with a ribozyme-expressing adenovirus diminution of hTERT mRNA, attenuation of telomerase activity, inhibition of net growth, and induction of apoptosis was found as well. Attenuation of telomerase activity increased the sensitivity of HBL-100 and MCF-7 clones specifically to inhibitors of topoisomerase. Likewise, expression of exogenous telomerase in originally telomerase-negative human fibroblasts decreased their sensitivity to topoisomerase poisons but not to a number of other cytotoxic drugs. The data validate a ribozyme approach for telomerase inhibition therapy in cancer and suggest that it might be combined advantageously with topoisomerase-directed chemotherapy.

Adenocarcinoma↗

PubMed2001

Suppression of the ribosomal L2 gene reveals a novel mechanism for stress adaptation in soybean.

Pseudomonas syringae pv. glycinea bacteria or zoospores of the fungus Phytophthora sojae were used to trigger a hypersensitive reaction (HR) in cell cultures of soybean (Glycine max [L.] Merr. cv. Williams 82). During a screen for genes that show an altered expression as a response to dying neighbour cells we have identified a gene fragment that is specifically but transiently down-regulated in an HR. The corresponding cDNA codes for the ribosomal protein L2 (rpL2) of 80S ribosomes, which is essential for the peptidyl-transferase activity. Two gene copies of rpL2 exist in soybean and both genes are transcribed. The temporary down-regulation of the rpL2 genes is followed by a transient block in the synthesis of new proteins as visualised by pulse-labelling experiments using 35S-amino acids. The same basic phenomenon was also found after treatment of soybean cells with other stress-causing compounds such as elicitors or heavy metals. It is suggested that the transient block in protein synthesis allows a more rapid depletion of, for example, signal molecules with a short half-life time and thus leads to a faster adaptation of the cellular protein inventory to the new environmental conditions.

Adaptation, Physiological↗

PubMed2001

WY-14,643 and other agonists of the peroxisome proliferator-activated receptor reveal a new mode of action for salicylic acid in soybean disease resistance.

Inoculation of soybean (Glycine max [L.] Merr.) cell-suspension cultures with avirulent bacteria results in a salicylic acid (SA)-controlled programmed cell death (pcd). To unravel the nature of the SA-dependent step in pcd, a screening procedure for complementing compounds was performed. Diverse chemicals that are well known as activating ligands for orphan receptors in animals, particularly receptors of the PPAR (peroxisome proliferator-activated receptor) subfamily, were found to be active. These include the compounds WY-14643, flufenamic acid, LY-171883, tolbutamide, indomethacin and clofibrate. A new marker gene (DD-CA9) from soybean that is induced in the hypersensitive reaction by SA and by PPAR ligands was isolated by differential display, and showed homology to antifungal lectins. In plants, SA is also involved in a signal transduction pathway leading to systemic acquired resistance (SAR). The PPAR ligands which act on the pcd pathway for plant resistance induce a beta-1,3-glucanase gene in soybean at high concentrations but do not induce marker genes of the SAR pathway such as the PR-1 gene in tobacco or Arabidopsis. Thus SA seems to act on two independent plant defence pathways that can now be separately activated by synthetic compounds. We propose a model for the control of pcd by SA in soybean, in which SA induces the transcription of (novel) genes required for the final completion of the cell death program.

Amino Acid Sequence↗

PubMed2001

Binding inhibition of type 1 fimbriae to human granulocytes: a flow cytometric inhibition assay using trivalent cluster mannosides.

The binding of type 1 fimbriae from Escherichia coli to vital human neutrophilic granulocytes was inhibited by synthetic trivalent cluster mannosides. Binding of type 1 fimbriae was measured in a flow cytometric assay. Based on the molarity of mannosyl residues, the clusters exceed the inhibitory potency of methyl alpha-D-mannoside by a factor of more than 1,000 and the inhibitory potency of p-nitrophenyl alpha-D-mannoside by a factor of more than 10. The inhibition studies indicate that the trivalent cluster mannosides are very potent inhibitors of the binding of type 1 fimbriae to human neutrophilic granulocytes. Based on their defined structure, cluster mannosides are well suited for characterizing the molecular interactions of mannose-sensitive fimbriae with their cell membrane receptors.

Bacterial Adhesion↗

PubMed2001

Differential and age-dependent expression of hyperpolarization-activated, cyclic nucleotide-gated cation channel isoforms 1-4 suggests evolving roles in the developing rat hippocampus.

Hyperpolarization-activated cation currents (I(h)) are found in several brain regions including thalamus and hippocampus. Important functions of these currents in promoting synchronized network activity and in determining neuronal membrane properties have been progressively recognized, but the molecular underpinnings of these currents are only emerging. I(h) currents are generated by hyperpolarization-activated, cyclic nucleotide-gated cation channels (HCNs). These channel proteins are encoded by at least four HCN genes, that govern the kinetic and functional properties of the resulting channels. Because of the potential impact of I(h)-mediated coordinated neuronal activity on the maturation of the functional hippocampal network, this study focused on determining the expression of the four members of the HCN gene family throughout postnatal hippocampal development at both the regional and single cell level.The results of these experiments demonstrated that HCNs 1, 2 and 4 are differentially expressed in interneuronal and principal cell populations of the rat hippocampal formation. Expression profiles of each HCN isoform evolve during postnatal development, and patterns observed during early postnatal ages differ significantly from those in mature hippocampus. The onset of HCN expression in interneurons of the hippocampus proper precedes that in the dentate gyrus, suggesting that HCN-mediated pacing activity may be generated in hippocampal interneurons prior to those in the hilus. Taken together, these findings indicate an age-dependent spatiotemporal evolution of specific HCN expression in distinct hippocampal cell populations, and suggest that these channels serve differing and evolving functions in the maturation of coordinated hippocampal activity.

Aging↗

PubMed2001

Ribozyme-mediated telomerase inhibition induces immediate cell loss but not telomere shortening in ovarian cancer cells.

Telomerase is a promising target for human cancer gene therapy. Its inhibition allows telomere shortening to occur in cancer cells, which in turn is thought to trigger delayed senescence and/or apoptosis. We tested whether telomerase inhibition might have additional, immediate effects on tumor cell growth. Ovarian cancer cell lines with widely differing telomere lengths were efficiently transduced with an adenovirus expressing a ribozyme directed against the T motif of the catalytic subunit of human telomerase, hTERT. Three days after transduction, telomerase activity was significantly reduced and massive cell loss was induced in mass cultures from all four ovarian cancer cell lines tested, whereas transduction of telomerase-negative human fibroblasts did not attenuate their growth. The kinetics of induction of cell death in cancer cells was not significantly dependent on telomere length, and telomeres did not shorten measurably before the onset of apoptosis. The data suggest the existence of a "fast-track" mechanism by which diminution of telomerase can interfere with cancer cell growth and induce cell death, presumably by apoptosis. This phenomenon might be a consequence of the telomere capping function provided by telomerase in tumor cells. Uncapping of telomeres by ribozyme-mediated inhibition of telomerase bears therapeutic potential for ovarian cancer.

Adenoviridae↗