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Biomedical subjects

A Berndt

Publications and source records attributed to A Berndt.

86 records · Page 5Linked to original sources

Appearance of the myofibroblastic phenotype in Dupuytren's disease is associated with a fibronectin, laminin, collagen type IV and tenascin extracellular matrix.

The proliferative nodules of Dupuytren's disease are electron microscopically characterized by the occurrence of myofibroblasts with a basal lamina-like material. As reported in the literature, immunohistochemical investigations showed a fibronectin matrix but failed to demonstrate laminin. This discrepancy between electron microscopic features and immunohistochemical findings prompted us to examine the composition of extracellular matrix (fibronectin, laminin, collagen type IV and tenascin) in relation to the myofibroblast phenotype in proliferative nodules from 13 native surgical specimens of nodular palmar fibromatosis (Dupuytren's disease). The immunohistochemical staining for fibronectin was positive within the whole palmar aponeurosis and was particularly intense in the proliferative areas, whereas laminin, collagen type IV and tenascin labelling was restricted to the alpha-smooth muscle actin-positive proliferative nodules. To exclude definitively an unspecific laminin labelling, SDS-PAGE and immunoblot were performed. The electrophoretic pattern of Dupuytren's disease tissue revealed laminin and was in congruence with human placental tissue used as positive control. The results substantiate an extracellular matrix formation by myofibroblasts with fibronectin, laminin, collagen type IV and tenascin as constituents. Therefore, laminin expression can no longer be considered to be a distinguishing feature between myofibroblasts and smooth muscle cells.

Cell Adhesion Molecules, Neuronal↗

A simple method for the determination of articaine and its metabolite articainic acid in dentistry: application to a comparison of articaine and lidocaine concentrations in alveolus blood.

This study was undertaken to develop a time- and cost-effective method for the detection of articaine and articainic acid in alveolus blood by high-performance liquid chromatography with a simple method of sample pretreatment. To overcome the problem of very rapid hydrolysis a method for controlling hydrolysis in vitro after blood sampling was developed. Blood samples were withdrawn from the alveolus of the upper molars 2-14 min after submucous injection of articaine (2.0 ml 4%) or identical injection of lidocaine (2.0 ml 2%). The higher blood levels found for articaine correspond to the higher concentration of the drug in the injection solution. A relationship between the serum concentration of articaine and lidocaine, respectively, and the time between injection and blood sampling could be established.

Alveolar Process↗

Laminin matrix formation and S-100 protein and/or desmin-positive cells in malignant fibrous histiocytoma (MFH).

16/30 human storiform-pleomorphic malignant fibrous histiocytomas (MFH) showed a focal pericellular immunostaining for laminin. 14/16 of these laminin-positive tumours additionally revealed an atypical cellular differentiation (desmin- and/or S-100 protein-positive cells). The significance of focal laminin positivity along with atypical, non-entity specific differentiated cells is discussed before the background of laminin as being an indicator and promoter of differentiation in MFH. The limited value of a laminin detection in MFH for solving differential diagnostic questions (MFH versus other poorly differentiated sarcomas with basement membrane formation) has been pointed out.

Cell Differentiation↗

Pharmacokinetics of trapidil (Rocornal) in patients with chronic liver disease.

The pharmacokinetics of trapidil (Rocornal, Deutsches Hydrierwerk Rodleben GmbH) were studied in 15 patients with chronic liver disease (12 patients with hepatic cirrhosis, 2 patients with alcoholic fatty liver, one patient with liver fibrosis). Trapidil was given orally (200 mg, Rocornal dragees 100 mg) as well as intravenously (100 mg) in random order. Serum samples were analyzed for trapidil by HPLC. The pharmacokinetic parameters were compared with the parameters of 12 healthy volunteers, investigated by Weiss [1991]. Total plasma clearance was decreased significantly in patients with hepatic cirrhosis (99.6 ml/min vs 273.1 ml/min in controls and 255.3 ml/min in patients with non cirrhotic liver disease). However, there was no difference in clearance between patients with compensated and patients with decompensated cirrhosis. Clearance and aspartate aminotransferase activity correlated inversely. In addition, in some of the patients suffering from portal hypertension delayed absorption was observed, but the difference did not reach statistical significance. The volumes of distribution were significantly lower in patients with non alcoholic cirrhosis (19.9 l vs 36.8 l in controls and 41.0 l in patients with alcoholic cirrhosis). It might be concluded from this study, that dosage adjustments are necessary in treatment of patients with cirrhosis. In patients suffering from portal hypertension an intravenous administration should be prefered.

Chromatography, High Pressure Liquid↗

[Retrusive joint function and stability range of the mandible].

In CO the mandible possesses a retrusive function, although this is hardly visible to the naked eye. Yet this function is equal in importance with the protrusive function for the mechanical stability of the mandible in CO while muscular forces are acting. It is theoretically concluded and empirically demonstrated herein that any force, whose line of action is within a certain area of stability, acts to secure the mandible in CO. The limits and range of this area as well as its clinical implications are discussed.

Biomechanical Phenomena↗

Loss of monocyte membrane receptors in patients with SLE.

Following an 80-min cold treatment of monocytes and their subsequent heating at 37 degrees C a part of the Fc and C3 receptors is shed from the cells into the serum-free medium. However, while the reduced expression of cell membrane Fc receptors is regenerated at 37 degrees C in 4-8 hr, that of the C3 receptors is not. Initially, the Fc receptor expression of monocytes for patients with SLE is greater than that of controls and after shedding it increases to the level of controls at 37 degrees C in 4-8 hr. The expression and the regeneration of C3 receptors are equivalent to those of controls. The phagocytic ability of patient monocytes is lower than that of controls and the difference also remains after heat treatment.

Female↗

Dose dependent tiracizine disposition in healthy volunteers: serum and urine kinetics and dose related ECG-changes.

The pharmacokinetics of tiracizine, a new class I antiarrhythmic agent, and 3 of its metabolites were assessed in serum and urine of 8 healthy extensive metabolisers after single oral administration of 50, 100, and 200 mg tiracizine hydrochloride. Additionally, tiracizine induced ECG-changes were compared between the different doses. With increasing doses enhancement of AUC and Cmax of tiracizine and its metabolites revealed a slight deviation from linearity indicated by exceeding the upper limits of the 95% nonparametric confidence interval set by 0.8-1.2 for the ratio (dose corrected parameters after the 100 and 200 mg dose, respectively)/(parameters after 50 mg). The increase of the dose corrected parameters after the 200 mg dose was about 1.3-fold compared with the 50 mg parameters for the parent compound as well as its metabolites. The significant decrease of the renal clearance of all 4 substances with increasing doses indicates that saturable tubular secretion mainly accounts for non-linearity. Due to the occurrence of non-linear (tubular secretion) as well as linear (glomerular filtration, hepatic metabolism) elimination in parallel, however, it is concluded that saturable tubular secretion is of minor importance at higher doses and should not be overestimated. However, there was some evidence for saturable hepatic tiracizine metabolism in 4 of the 8 participants. Therefore, a fall of apparent intrinsic clearance has also to be taken into consideration, especially at higher doses. PQ- and QRS-intervals were prolonged in a dose dependent manner and culminated at 1 h after drug intake. QTc-time, however, remained unchanged. A log-linear relationship between serum concentrations of the parent compound and PQ- as well as QRS-time is suspected for serum levels about 80 ng/ml, but has to be confirmed by individual pharmacokinetic-pharmacodynamic modelling. PQ- and QRS-intervals might be suitable for tiracizine therapeutic monitoring.

Adult↗

Studies of the influence of ochratoxin A on immune and defense reactions in the mouse model.

In the mouse model, the mycotoxin ochratoxin A has a non-selective suppressive effect on various immune and defence reactions. Apart from weight depression, lymphopenia, neutrophilia and eosinophilia, antibody-producing cells, antibody titres in blood serum and phagocytosis of Escherichia coli by blood phagocytes become suppressed. Moreover, immunized animals show a lower survival rate after experimental infection with Pasteurella multocida as well as an increase in oxygen radicals in blood cells.

Animals↗

Fetal fibronectin: a new screening-marker for bladder cancer?

Early detection of transitional cell carcinoma (TCC) of the urinary bladder is essential for effective treatment. While several serum markers have been evaluated, none have been widely accepted for practical clinical use. Thus, urinary markers have been introduced and investigated to detect the evidence of bladder cancer. But sensitivity and specificity range around 80% respectively. In a prospective study we evaluated fetal fibronectin in the urine of patients with TCC of the urinary bladder. The positivity of oncofetal fibronectin was measured in morning urine samples by membrane immunoassay. This FFN membrane immunoassay is a qualitative test, a solid-phase immunogold assay. A positive sample will result in a single spot after binding of the oncofetal fibronectin-immunogold complex to the membrane containing a monoclonal antibody specific to oncofetal fibronectin (FDC-6, which specifically recognizes III-CS region). The morning urine samples were collected from patients with TCC before they underwent transurethral resection (n=40, 34 non-invasive and 6 invasive carcinomas) and healthy controls (n=20). Oncofetal fibronectin was investigated in the surgical samples by immunohistochemistry (antibody FDC-6, APAAP technique). We found a positive result for oncofetal fibronectin in 38/40 patients with transitional cell carcinoma of the urinary bladder. Two patients with a small pTaG1-TCC showed negative results. In the urine of healthy controls no positive results were detected. Thus, there is a sensitivity of 95% and a specificity of 100%. The TCC was demonstrated as a source of oncfn. To our knowledge this is the first study showing that patients with an evident TCC have a demonstrable amount of oncofetal fibronectin in the urine. We conclude that a positive result is common in TCC-patients. The sensitivity and specificity of this test seems to be extraordinarily high. Because of the small number of cases further studies are required.

Adult↗

Combination of competitive exclusion and immunization with an attenuated live Salmonella vaccine strain in chickens.

To use the advantages of both the competitive exclusion (CE) technique and immunization with a live Salmonella vaccine, the combination of these methods was studied. Specific-pathogen-free chickens were pretreated by combined or single administration of a CE culture and a commercial live Salmonella typhimurium vaccine on days 1 and 2 of life and challenged with Salmonella typhimurium on day 3 to study the exclusion effect by both the CE preparation and the Salmonella vaccine. The exclusion effect by the CE culture combined with the immunologic effect by the live vaccine was studied after challenge of the birds on day 43 of age. The number of challenge organisms in ceca was used to evaluate the efficacy of the pretreatment. The protective exclusion effect of the CE culture was substantial in very young chicks and still detectable in 6-wk-old birds. The attenuated Salmonella typhimurium vaccine produced only an initially occurring exclusion effect. Because the exclusion effect of the CE culture was considerably stronger than the exclusion effect of the attenuated Salmonella typhimurium vaccine, the combination of both did not result in an additive protective effect. In order to exploit the exclusion potential between Salmonella strains and to attain an additive exclusion effect by a CE culture and a vaccine strain, live Salmonella vaccines are needed that are sufficiently attenuated without affecting genes essential for colonization exclusion of other Salmonella organisms. In 6-wk-old birds, the exclusion effect by the CE culture combined with the immunologic effect by the live Salmonella vaccine resulted in a degree of protection considerably beyond that generated by the exclusive use of the two methods. The administration of the live Salmonella vaccine strain prior to or simultaneously with the CE culture revealed the best protective effect because such combinations ensure an adequate persistence of the vaccine strain as prerequisite for the expression of an exclusion effect in very young chicks and the development of a strong immune response affording protection in older birds.

Animals↗

Re-distribution of tenascin-C in the parotid acinar cells. An early marker of radiation-induced damage of salivary glands?

PURPOSE: In order to investigate the early changes in the expression of tenascin-C, following irradiation and the associated functional impairment of salivary glands. MATERIALS AND METHODS: Fifteen rabbits were used for the study. Five provided control parotid gland tissue and a further 10 rabbits were scintigraphically examined prior to and 24 h after 15/30 Gy. Glands were studied histologically using HE-staining and tenascin-C antibodies. RESULTS: Reduction in the salivary ejection fraction (SEF) was observed in all irradiated glands. Simultaneously, a marked re-distribution of tenascin-C expression was noticed. Reactivity detected in the intercalated, secretory ducts and perineurinal regions prior to radiation was noticed intracellularly after 24 h. Furthermore, nerves showed tenascin-C expression in the Schwann cells, but no longer perineurinally. Myofibroblasts were also observed in the stroma. CONCLUSION: This study proves the ability to predict functional disorders of salivary function as early as 24 h after radiation and provides evidence of the participation of tenascin-C in the pathological process of radiation-induced damage in salivary glands.

Animals↗

Saturable in vitro metabolism of articaine by serum esterases. Does it contribute to the persistence of the local anesthetic effect?

BACKGROUND AND OBJECTIVES: The amide-type local anesthetic articaine is unique in that hydrolysis to articainic acid by serum esterases is its main metabolic pathway. The purpose of the present investigation was to study the concentration dependence of this pathway in vitro. METHODS: To unbuffered (pH 8.2) as well as phosphate-buffered (pH 7.4) heated serum samples were added various amounts of articaine in the range 10-300 micrograms/mL. Concentrations of articaine and articainic acid were measured by high-performance liquid chromatography after incubating the samples at 37 degrees C for intervals ranging from 5 minutes to 6 hours after addition of articaine. RESULTS: The in vitro metabolism of articaine was shown to undergo pH-dependent Michaelis-Menten kinetics, indicating saturation at higher substrate concentrations. The Michaelis constant K(m) was determined as 175 micrograms/mL and 22.1 micrograms/mL and the maximum reaction rate Vmax as 2.1 micrograms/mL/min and 0.17 microgram/mL/min at pH 8.2 and pH 7.2, respectively. These results support previous in vivo observations that suggest saturable articaine metabolism, indicated by higher articaine/articainic acid metabolic ratio with higher articaine concentrations in alveolar blood after dental extraction. CONCLUSION: Local saturation of the serum esterases may contribute to the advantageous relationship between persistence of the local anesthetic effect and low systemic toxicity caused by the last systemic elimination of articaine (ie, its wide toxic therapeutic ratio).

Anesthetics, Local↗