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Biomedical subjects

A Werner

Publications and source records attributed to A Werner.

At least 127 records · Page 7Linked to original sources

Exercise training in aging: hemodynamic, metabolic, and oxidative stress evaluations.

The effects of exercise training on hemodynamic and metabolic parameters as well as on responses to oxidative stress in aged individuals are controversial. The aim of the present study was to investigate changes in heart hate, mean arterial pressure, vasoreactivity, and plasma levels of insulin and glucose in male aged Wistar rats submitted to exercise training for 11 weeks (1 h/d; 5 d/wk) in a treadmill. The isolated heart was perfused by H2O2, and oxidative stress was evaluated using thiobarbituric acid reactive substances. Cardiovascular functions were recorded with a data acquisition system (CODAS, 1 kHz). Trained aged rats were bradycardic as compared with sedentary aged rats (298+/-7 versus 336+/-16 bpm) but presented similar mean arterial pressure and vasoreactivity and plasma levels of insulin and of glucose, which were quantified by radioimmunoassay and colorimetric enzymatic test. Plasma levels of insulin and of glucose ratio were increased in trained aged rats (6.9+/-0.7 versus 3.5+/-0.4 in sedentary aged rats), and the response to oxidative stress was decreased (0.4+/-0.1 versus 0.7+/-0.1 nmol/mg protein in sedentary aged rats). These results showed that exercise training produced a lower resting heart rate as well as changes in metabolic and oxidative responses. This suggests a higher myocardium protection of trained than sedentary aged rats.

Aging↗

Inhibition of HIV-1 in cell culture by synthetic humate analogues derived from hydroquinone: mechanism of inhibition.

Humic acids are natural constituents of soil and ground water and mainly consist of mixtures of polycyclic phenolic compounds. A similar complex of compounds with a mean size of about 1000 Da, designated HS-1500, was synthesized by oxidation of hydroquinone. HS-1500 inhibited HIV-1 infection of MT-2 cells with an IC50 of 50-300 ng/ml and showed a mean cell toxicity of about 600 micrograms/ml. Inhibition of HIV-induced syncytium formation was observed at 10-50 micrograms/ml. Treatment of free and cell-attached HIV with HS-1500 irreversibly reduced its infectivity, whereas the susceptibility of target cells for the virus was not impaired by treatment prior to infection. The HIV envelope protein gp120SU bound to sepharose-coupled HS-1500 and could be eluted by high salt and detergent. HS-1500 interfered with the CD4-induced proteolytic cleavage of the V3 loop of virion gp120SU. Furthermore, binding of V3 loop-specific antibodies was irreversibly inhibited, whereas binding of soluble CD4 to gp120SU on virus and infected cells was not affected. In conclusion, our data suggest, that the synthetic humic acid analogue inhibits the infectivity of HIV particles by interference with a V3 loop-mediated step of virus entry.

Antiviral Agents↗

Pulsed field gradient NMR and nuclear magnetic relaxation studies of water mobility in hydrated collagen II.

Transverse nuclear magnetic relaxation and self-diffusion of water were measured in hydrated collagen II. Self-diffusion measurements were conducted by pulsed field gradient NMR (PFG NMR) and weighting of the different species in the signal by variable T2 relaxation in the experiment. Two fractions of water protons were detected, one with a short T2 value but high diffusivity and one with a long T2 value and low, completely restricted diffusion. The distance of the diffusion barriers was determined to be 2.3 microns. Possible reasons for the restriction in the movement of the water molecules in comparison with structural models of collagen II are discussed.

Collagen↗

Influence of filler parameters on the mechanical coherence of dental restorative resin composites.

Next to the presence of (chemical) coupling between filler and resin, filler particle size is important for the mechanical coherence of dental resin composites which are used for posterior restorations. In the range of the current composites a smaller particle size is desirable. The better mechanical coherence for composites with smaller particles found in an in vitro erosive wear test is probably related to the size of food fibres, which are part of the erosive medium. It appears that there is a critical value of the filler particle size (1.3-1.5 microns), under which the food fibres are not able to penetrate in the interparticle space, so the erosive capability of the erosive medium will be reduced.

Adhesiveness↗

Influence of enzymes and plaque acids on in vitro wear of dental composites.

The purpose of this investigation was to test the effect of an enzymatic and an acidic medium on in vitro wear of dental resin composites and an amalgam. Wear was evaluated in two-body and three-body wear conditions. The third body was a food slurry either in water, an esterase solution or an acid solution at a composition and concentration as found in caries active plaque fluid. In the two-body tests the slurry was left out. Under three-body wear conditions neither the enzyme nor the acids showed any significant (P < 0.05) effect on wear. Enzyme inactivation from a large excess of food constituents in the slurry or the absence of an effect from surface diffusion rates of the acids resulted in the lack of an effect on wear. The two-body/acids wear rates were statistically (P < 0.05) lower than the two-body/water wear rates caused by increased lubrication from the acids between sliding surfaces. A significant (P < 0.05) increase in wear was found in the two-body/enzyme experiments, showing that the enzymatic activity can start directly at the outer surface of the composites.

Acids↗

Renal Na/Pi-cotransporters.

Two non-homologous proximal tubular apical Na/Pi-cotransport systems (type I and type II) have been identified thus far by expression cloning. Subsequent studies provided evidence that the type II Na/Pi-cotransporter represents a target for the physiological and pathophysiological regulation of proximal reabsorption of phosphate. The exact role of the type I Na/Pi-cotransporter in proximal Pi-reabsorption and eventually also in the renal handling of other substrates, such as organic anions, is currently less clear and needs further investigation. Evidence was obtained that acute changes of brush border membrane Na/Pi-cotransport involves endo- and exocytic movement of type II Na/Pi-cotransporters. In particular, we elucidated if and how phosphorylation reactions are involved and defined the intracellular structures of the endo/exocytic apparatus involved. At the level of the gene it will be necessary to elucidate its organization in order to understand the mechanisms involved in chronic regulations of Na/Pi-cotransport related to the type II Na/Pi-cotransporter. Furthermore, for structural investigations of these integral membrane proteins, they have to be isolated in sufficient quantities. Thus far the type II cotransporter (NaPi-2) has been expressed in Sf9 insect cells [20], which may eventually allow a purification of this protein.

Animals↗

[Schwannoma of the obturatorius nerve as differential diagnosis in cystic adnexa tumors].

We report on a case of benign retroperitoneal schwannoma involving the obturator nerve. Discussing the difficulties of diagnosis and treatment the following became clear: 1.) Clinical examination, ultrasound and computed tomography are not helpful to differentiate a retroperitoneal schwannoma from a cystic ovarian tumour; this problem can perhaps be overcome by MR imaging. 2.) The diagnosis should be borne in mind in cases of retroperitoneal tumours of unclear origin. Appropriate surgery is necessary to avoid nerve damage and paralysis.

Aged↗

Epstein-Barr virus (EBV)-associated smooth-muscle tumor arising in a post-transplant patient treated successfully for two PT-EBV-associated large-cell lymphomas. Case report.

The association of Epstein-Barr virus (EBV) with smooth-muscle tumors was recently reported in the setting of acquired immunodeficiency syndrome (AIDS) and post-transplantation. We report a case of an EBV-associated smooth-muscle tumor arising in a post-transplant (PT) patient who previously was treated successfully for two EBV-associated PT large-cell lymphomas. A 4-year-old girl required cardiac transplantation for dilated cardiomyopathy when she was aged 23 months. Her PT regimen included cyclosporine, azothiaprine, and diltiazem. At 16 months PT, she presented with anemia, guaiac-positive stools, and an abdominal mass diagnosed as diffuse large-cell lymphoma of B-cell phenotype. Immunosuppressive therapy was reduced, and interferon and i.v. immunoglobulin were initiated. She rapidly developed signs of rejection, and a cardiac biopsy was performed, revealing grade IIIB rejection. Subsequently, immunosuppressive therapy increased. At 23 months PT, a biopsy was done of a large pelvic mass that was diagnosed as immunoblastic large-cell lymphoma. After treatment with chemotherapy and retinoic acid, the size of the mass markedly decreased. Follow-up computed tomography scan revealed multiple liver nodules. A needle biopsy of the liver showed a smooth-muscle tumor of indeterminate grade. Both the lymphomas and the smooth-muscle tumor contained EBV within > 95% of tumor cells by Epstein-Barr (EBER1) in situ hybridization, were of strain type A by Epstein-Barr nuclear antigen-2 (EBNA-2) polymerase chain reaction (PCR) and contained an identical 30 base-pair deletion (amino acids 346-355) of the latent membrane protein (LMP)-1 oncogene by PCR analysis. Notably, the initial large-cell lymphoma and the subsequent immunoblastic lymphoma each contained a unique p53 mutation, suggesting that they were distinct. These data suggest that the same virus contributed to the pathogenesis of both the malignant lymphomas and the smooth-muscle tumor.

Abdominal Neoplasms↗

Inhibition of experimental liver metastasis by combined treatment with tamoxifen and interferon.

The demonstration of estrogen receptors (ERs) in the liver has established it as a hormonally responsive organ. Estrogens have been imputed to have a role in the development of benign and malignant liver tumors. The detection of ERs in samples of normal liver tissue and in hepatocellular carcinomas suggested a treatment strategy with anti-hormonal drugs, i.e. tamoxifen, as used clinically for the treatment of breast cancer. The objective of this study was to test the effect of tamoxifen and tamoxifen in combination with other agents [5-fluorouracil (5-FU) and interferon (IFN)] against experimental liver metastases of human colorectal tumor cells xenografted into nude mice. A human colorectal tumor cell line, LoVo, was injected into the spleens of nude mice. This produces liver metastases in virtually 100% of the mice in 6-8 weeks. One week before tumor cell implantation, all mice were ovariectomized. Treatment was started 3 days after the intrasplenic injections. This consisted of 5 mg tamoxifen pellets (60-day release) implanted s.c., 5-FU given i.p. once a week for 4 weeks on a 46 mg/kg basis and IFN given s.c., daily for 4 weeks, 3 x 10(5) units/injection. The effect of tamoxifen alone on liver metastases was not significantly different from untreated controls. Tamoxifen in combination with IFN and 5-FU, however, resulted in 50-67% inhibition of liver metastases, as compared with the controls. The effectiveness of the treatment was in the order: tamoxifen + IFN > tamoxifen + 5-FU + IFN > tamoxifen + 5-FU. Thus, IFN may be useful as a potentiating agent in combination with tamoxifen for the treatment of estrogen-dependent tumors.

Adenocarcinoma↗

Na-Pi cotransport in flounder: same transport system in kidney and intestine.

The cloning of a renal Na-Pi contransport in system from winter flounder (P eudopleuronectes americanus) has recently been reported. We used this information to answer the questions 1) what is the distribution of the transport protein along the nephron? and 2) how are renal and intestinal transporters related? The distribution of the flounder NaPi-II protein was tested using two antisera raised against partial sequences (amino acids 1-14 and 388-441) of the transporter. Antibody-specific fluorescence was detected at the basolateral membrane of epithelial cells in the proximal tubular segment PII. Two clones corresponding to the renal Na-Pi cotransporter were isolated from a flounder intestinal cDNA library. Their functional properties were determined using Xenopus laevis oocytes. The apparent affinities for Pi [Michaelis constant (K(m)) = 0.063 mM] and Na (K(m) = 45.3 mM), as well as the pH dependency (increasing transport activity with increasing pH), showed the same characteristics in both intestinal and the renal systems. Sequence analysis revealed that the two intestinal clones were 100% homologous to the renal cDNA, Flounder NaPi-II-specific immunofluorescence was observed predominantly at the apical membrane on intestinal cross sections. We report the cloning and expression of the first intestinal Na-Pi cotransport system. This transporter belongs to the small group of proteins that exhibit the same function in the apical and the basolateral membranes of different cells.

Amino Acid Sequence↗

Early and long-term wear of conventional and resin-modified glass ionomers.

Various studies have shown that glass ionomers are susceptible to brittle fracture and acid conditions and that they undergo long-term changes in their mechanical properties. Little information is available on how brittleness, acid susceptibility, and long-term changes are reflected in the wear characteristics of glass ionomers. The purpose of this study was to evaluate long-term changes in conventional glass ionomers, metal-reinforced glass ionomers (including a cermet), and (light-curing) resinmodified glass ionomers by wear experiments simulating the wear process in occlusal contact-free areas. The wear tests were conducted periodically over a period of one year. In addition, wear was determined after one year at a pH of 5 or 6, for assessment of acid susceptibility, and at a condition as found in the occlusal contact areas. All materials showed high early-wear rates which decreased significantly during the one-year test period. This long-term process may be related to a slow progression of the acid-base reaction extending over several months. At each stage, the resinmodified glass ionomers wore significantly faster than the acid-base setting glass ionomers. Most of these materials were not affected at a pH of 6.0, while at a pH of 5.0 only the conventional and the metal-reinforced glass ionomers showed increased wear. Direct contacts with the antagonist led to a significant increase in wear in comparison with contact-free wear, probably as a result of sub-surface fatigue phenomena. In view of the unfavorable wear characteristics of the resin-modified glass ionomers and the high early wear of the conventional glass ionomers, including the metal-reinforced glass ionomers, it was concluded that none of these materials can yet be recommended for use in high-stress-bearing situations.

Aluminum Silicates↗

[Does interferon-alpha enhance the effect of tamoxifen-medroxyprogesterone acetate and hydroxyflutamide on in vitro tumor cells?].

In our laboratory the influence of tamoxifen, medroxyprogesterone acetate (MPA) and hydroxyflutamid with and without interferon alpha (IFN) was tested on the proliferative capacity of two breast and one ovarian cancer cell line and three ovarian cancer tissues in the colony assay described by Hamburger and Salmon. The following results were seen: 1. Testing the four drugs alone in 6 different cell cultures, in vitro growth inhibition of more than 30% was seen 3 respectively 4 times. Growth inhibition of more than 50% could be shown only in particular cases. The higher dose of an active substance led up to three times more in comparison to the set growth restraint than the smaller dose. A reaction depending on the concentration was seen. 2. The combination of IFN and tamoxifen could not really increase the antiproliferative capacity of each substance alone. Nevertheless we were able to show a significant augmentation of the cell-growth inhibiting effect of MPA or hydroxyflutamid when it was given together with IFN: the increased antitumor activity was evident if cells were tested which showed progesterone-(PR) or androgenereceptors (AR). The results indicate that positive interactions of IFN and MPA or IFN and hydroxyflutamid are possible. Although an augmentation of the activity of tamoxyfen by IFN was not found it should be stressed that the schedule of treatment seems to be clearly critical.

Androgen Antagonists↗