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Biomedical subjects

A Martens

Publications and source records attributed to A Martens.

At least 37 records · Page 2Linked to original sources
PubMed1999

Effects of nabumetone compared with naproxen on platelet aggregation in patients with rheumatoid arthritis.

OBJECTIVE: To test the hypothesis that nabumetone (a partially selective cyclooxygenase-(COX)-2 inhibitor) has less effect on platelet aggregation than naproxen (a non-selective COX-inhibitor) in patients with rheumatoid arthritis (RA). METHODS: A crossover study in 10 RA patients was performed, using either nabumetone or naproxen for two weeks, and, after a washout period of two weeks, the other drug during another two weeks. Platelet aggregation studies were performed and bleeding time was assessed before and after each treatment period. RESULTS: Maximum platelet aggregation induced by epinephrine and by collagen was significantly more reduced after the use of naproxen than of nabumetone; secondary aggregation induced by ADP and epinephrine disappeared more often by naproxen than by nabumetone. Bleeding times were not influenced. CONCLUSION: COX dependent platelet aggregation in RA patients seems to be more inhibited by naproxen than by nabumetone. This may be relevant for patients requiring non-steroidal anti-inflammatory drug treatment but who have an increased risk of bleeding as well.

Adolescent↗
PubMed1998

Constitutive internalization and association with adaptor protein-2 of the interleukin-6 signal transducer gp130.

The transmembrane protein gp130 is the common signalling receptor subunit for the interleukin-6 (IL-6)-type cytokines. It has recently been shown that the cytoplasmic domain of gp130 contains a dileucine internalization motif and that endocytosis of gp130 occurs signal-independent. Here, we have studied whether gp130 itself undergoes constitutive internalization or whether its endocytosis is stimulated by formation of the IL-6/IL-6R/gp130 complex. Using two different assays, we found that gp130 is internalized independent from IL-6/IL-6R stimulation. In addition, we show that gp130 is constitutively associated with the cell surface adaptor complex AP-2. Our findings strongly suggest endocytosis of gp130 to be constitutive.

Adaptor Protein Complex alpha Subunits↗
PubMed1998

Soluble IL-6 receptor potentiates the antagonistic activity of soluble gp130 on IL-6 responses.

Soluble receptors for several cytokines have been detected in body fluids and are believed to modulate the cytokine response by binding the ligand and thereby reducing its bioavailability. In the case of IL-6, the situation is more complex. The receptor consists of two components, including a ligand-binding alpha-subunit (IL-6R, gp80, or CD126), which in its soluble (s) form (sIL-6R) acts agonistically by making the ligand accessible to the second subunit, the signal transducer gp130 (CD130). Soluble forms of both receptor subunits are present in human blood. Gel filtration of iodinated IL-6 that had been incubated with human serum revealed that IL-6 is partially trapped in IL-6/sIL-6R/sgp130 ternary complexes. sgp130 from human plasma was enriched by immunoaffinity chromatography and identified as a 100-kDa protein. Functionally equivalent rsgp130 was produced in baculovirus-infected insect cells to study its antagonistic potential on four different cell types. It was found that in situations in which cells lacking membrane-bound IL-6R were stimulated with IL-6/sIL-6R complexes, sgp130 was a much more potent antagonist than it was on IL-6R-positive cells stimulated with IL-6 alone. In the latter case, the neutralizing activity of sgp130 could be markedly enhanced by addition of sIL-6R. As a consequence of these findings, sIL-6R of human plasma must be regarded as an antagonistic molecule that enhances the inhibitory activity of sgp130. Furthermore, in combination with sIL-6R, sgp130 is a promising candidate for the development of IL-6 antagonists.

Adjuvants, Immunologic↗
PubMed1998

Conservative and surgical treatment of tibial fractures in cattle.

Ninety-five cattle with tibial fractures, all but one with a unilateral fracture, were examined between 1990 and 1994. The feasibility of repairing the fracture was assessed radiographically, also taking into account the bodyweight and value of the animal. Twenty-two cattle were slaughtered. Conservative treatment with stall confinement and/or a splint or cast was applied in 18 cases, with satisfactory results in eight of them (44 per cent). They were fattened to normal bodyweight, but they all had a severe deformity of the affected leg. In 55 animals, the fractures were fixed externally with Steinmann pins and methylmethacrylate bridges under image-intensified fluoroscopy. Ten of them could not bear weight on the affected leg and were slaughtered before the pins were removed. In the remaining 45 animals the pins were removed after a mean (sd) period of 71 (14) days. Four animals re-fractured the affected leg shortly after the pins were removed and six others were slaughtered prematurely because of inadequate weight bearing. The results were successful in 35 cases (64 per cent). Slight deviations of the affected leg and/or the contralateral leg were often observed. The overall survival rate of the cattle with tibial fractures was 45 per cent.

Animals↗
PubMed1998

Radiologic investigations and pathologic results of experimental chronic pancreatitis in cats.

RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate a variety of methods to induce chronic pancreatitis and its radiologic expression by experimentally inducing this condition in cats. MATERIALS AND METHODS: Chronic inflammatory and fibrosing pancreatitis was produced in cats by intraductal injection of 1.5 mL of 94% ethanol in one group or by a combination of intraductal and intraparenchymal injection of ethanol together with partial obstruction of the main pancreatic duct to 70% of its original lumen by fixation of a small catheter in the papilla. For comparison, other cats underwent total obstruction of the main pancreatic duct. All groups, as well as untreated control cats (n = 3), underwent repeat laparotomy to obtain biopsy specimens. RESULTS: Cats with total obstruction showed progressing fibrosis with dilatation of ductules occasionally infiltrated with granulocytes. From 26 weeks on, acini and islets of Lnagerhans became atrophic. Radiographs showed progressive but diffuse dilatation of ducts, ductules, and side branches. Cats from the other two groups had interlobular inflammation and fibrosis with flattened and irregular ductular epithelium. Later, ductular proliferation occurred, interstitial inflammation subsided, and fibrosis increased. Radiographs showed very irregular ducts and ductules with stenosis and dilatation. From 26 weeks on, no substantial differences were observed between the cats who received only intraductal injection of ethanol and the cats who underwent the combination of procedures. CONCLUSION: The histopathologic and radiographic alterations that evolved from damage to the ductal epithelium in the cat resembled the features of chronic pancreatitis in humans and differed from those caused by total obstruction of the main pancreatic duct in cats.

Animals↗
PubMed1997

Soluble interleukin 2 receptor and soluble CD8 levels in previously treated human immunodeficiency virus-negative hemophiliacs multiply transfused with a monoclonal antibody-purified factor VIII concentrate.

BACKGROUND: Serum levels of the soluble interleukin 2 receptor (sIL-2R) and soluble CD8 (sCD8) may be used as markers of T-cell activation. The course of serum levels of sIL-2R and sCD8 in hemophiliacs who were treated first with an intermediate-purity factor VIII concentrate and then with a monoclonal antibody (MoAb)-purified factor VIII concentrate are reported. STUDY DESIGN AND METHODS: Serum samples taken before the administration of the MoAb-purified concentrate and after 2 and 5 years of its administration to 20 human immunodeficiency virus-negative patients with hemophilia A were analyzed. Eighteen healthy age-matched men were used as controls. RESULTS: The sIL-2R and sCD8 levels were higher in patients treated with intermediate-purity concentrates than in controls (p = 0.006 and p = 0.0005, respectively). The sIL-2R levels showed a decrease after 5 years of treatment with the MoAb-purified concentrate (p = 0.018 for the difference between 2 and 5 years), to levels that were not significantly different from those in controls. Although sCD8 levels tended to decrease at 5 years (p = 0.09, for the difference between 2 and 5 years), they remained higher than those in controls (p = 0.0005 and p = 0.0016 at 2 and 5 years, respectively). The ratio of sCD8 and sIL-2R tended to increase between 2 and 5 years (p = 0.07). The sIL-2R and sCD8 levels were not related to the numbers of T-lymphocytes and HLA-DR-positive T-lymphocytes in peripheral blood. Nor was a relation demonstrated between sIL-2R levels and CD4-positive cell numbers or between sCD8 levels and CD8-positive cell numbers. Although a relation with chronic hepatitis C cannot be excluded, it seems more likely that changes in sIL-2R levels are due to the use of the MoAb-purified concentrate. CONCLUSION: Elevated levels of sIL-2R and sCD8 were found in multiply transfused human immunodeficiency virus-negative hemophiliacs. After treatment was changed to the use of a MoAb-purified concentrate. sIL-2R levels decreased. These findings suggest a change in immune stimulation that is remarkable, because signs of activation in the effector phase seem to have continued despite normalization in the proliferative phase.

Adult↗
PubMed1996

Surgical treatment of urethral dilatation in seven male cattle.

The surgical treatment of urethral dilatation in the perineal region of seven young Belgian blue bulls is described. Urethrostomy under local anaesthesia in the standing animal resulted in a successful outcome in three of them. The possible aetiological factors and consequences of this syndrome are discussed.

Animals↗
PubMed1995

Surgical aspects of intestinal atresia in 58 calves.

Fifty-eight calves with intestinal atresia at different sites were treated surgically. In only four of the animals the anal opening was reconstructed directly in the perineal region. In the remaining cases the final extent of the atresia was confirmed by a right flank laparotomy and in seven calves an anal opening was made in the perineal region and in seven calves the opening was made in the right flank. The remaining 40 calves were euthanased for different reasons. Seven of the 18 surgically corrected animals made a satisfactory recovery.

Animals↗
PubMed1994

New NO-donors with antithrombotic and vasodilating activities, V: Oligonitroso sydnone imines.

Nine 4,4'-bis- and four 4,4'-tris-N-nitroso syndrome imines were synthesized. The sydnone imine moiety is connected either by aromatic 1,3-phenylene or 1,3,5-benzene or aliphatic methylene or propylene bridges. Compared to the corresponding sydnone imines the collagen induced platelet aggregation inhibiting activity is increased by several orders of magnitude by the nitroso derivatives. The most potent compound bears a hexyl substituent in 3-position (1d: IC50 = 0.05 mumol/L). These data show that aromatic bridges (1d, 2d) are more favourable than aliphatic ones (4b). This indicates the mutual influence of the nitroso-imino moieties via the aromatic bridges. In the series of 3,3'-bis-nitrososydnone imines (13 compounds) mostly additive effects of the nitroso groups are seen. The activities range from IC50 = 0.2 mumol/L (5i; 1,3-xylene bridge) to IC50 = 8 mumol/L (5b; trimethylene bridge). The differences suggest different affinities to the platelet membrane.

Animals↗
PubMed1994

Diagnostic value of plasma levels of tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) in newborns with sepsis.

The aim of this study was to examine if TNF alpha and IL-6 plasma levels could be of value in diagnosing neonatal sepsis. Tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) plasma levels were determined in 15 newborn infants with confirmed sepsis (group I), 18 with suspected sepsis (group II) and 22 control infants (group III). In 33 newborns, initially suspected of having sepsis (groups I and II), a positive test result for plasma concentration of TNF alpha (> 70 pg/ml) had a sensitivity of 73% and a specificity of 94%. A positive test result for IL-6 (> 500 pg/ml) had a sensitivity of 80% and a specificity of 78%. When plasma levels of TNF alpha and IL-6 were combined for the diagnosis of neonatal sepsis, a positive test result for both tests had a sensitivity of 60% and a specificity of 100%. When both tests are positive the diagnosis of neonatal sepsis is almost certain (likelihood ratio = infinity). The combination of TNF alpha and IL-6 determinations appears to be a good predictor of neonatal sepsis.

Biomarkers↗
PubMed1993

Platelet aggregation inhibiting and anticoagulant effects of oligoamines, XIX: 4,4'-Phenylene-bis-sydnone imines.

Fourteen 4,4'-m-phenylene- and two 4,4'-p-phenylene-bis-sydnone imine hydrochlorides have been synthesized. All compounds exhibited good solubility in water. In the m-series the 3-(3-phenylpropyl)-derivative 5c and the 3-hexyl compound 5l showed antiplatelet activities at or below 10 mumol/L (IC50, Born-test with collagen). The corresponding p-compounds had the same (6l) or slightly lower (6c) activity. No effect on the fibrin formation (Quick-test) could be observed.

Anticoagulants↗
PubMed1993

Platelet aggregation inhibiting and anticoagulant effects of oligoamines, XX: 4,4',4''-(1,3,5)-benzene-tris-sydnone imines.

The synthesis of ten tris-sydnone imine derivatives, unknown up to now, is described. All compounds are alkyl or arylalkyl substituted in 3-position of the sydnone imine. The most powerful agent was the 3-propyl derivative 6c. It inhibits the aggregation of human platelets induced by collagen in a concentration of 1 mumol/L half maximally. Its N-ethoxycarbonyl derivative 7c, which was designed as a prodrug, showed only small antithrombotic effects in rats. The reason for this low degree of activity is discussed.

Animals↗
PubMed1993

Platelet aggregation inhibiting and anticoagulant effects of oligoamines, XXI: 4,4'-Alkylene-bis-sydnone imines.

Two methylene-, seven ethylene-, eleven propylene- and two 4,4'-butylene-bis-sydnone imines have been synthesized and tested for their antiplatelet (Born-test, collagen) and anticoagulant (Quick-test) activity in vitro. The most active compounds were found in the ethylene and propylene series. The most favourable substituents in 3-position of the sydnone were hexyl to octyl or phenylethyl to phenylbutyl groups. Six compounds exhibit an IC50 < or = 10 mumol/L against platelet aggregation. Three compounds showed an IC75 < or = 200 mumol/L concerning the fibrin formation (Quick delta t > or = 7 s).

Anticoagulants↗
PubMed1993

Platelet aggregation inhibiting and anticoagulant effects of oligoamines, XXII: Bisoxazol-, bisimidazol-, bisthiazol- and oligo-1,2,4-thiadiazolimines.

One mesoionic 4,4'-propylene-bis-oxazol-5-imine (5), two 2,2'-m-phenylene-bis-imidazol-4-imines (9a,b), five 4,4'-benzene-bis-(and tris)-thiazol-2-amines (13a,b, 14a-c) and 14 3,3'-benzene-bis-(and tris)-1,2,4-thiadiazolimines (18a-o) were synthesized and assayed for their antiplatelet and anticoagulant activities. The most potent compound was the tris-thiadiazole derivative 18m which inhibited the aggregation of platelets induced by collagen at a concentration of 10 mumol/L by 50 percent (Born-test). No anticoagulant effects (Quick-test) were observed up to 400 mumol/L. In the thiazolamine series combined antiplatelet and anticoagulant activities were seen.

Anticoagulants↗
PubMed1993

Phase I/II study of low-dose intravenous OKT3 and subcutaneous interleukin-2 in metastatic cancer.

In a phase I/II study the safety, immunostimulatory and antitumor effects of a combined OKT3/interleukin 2 (IL-2) treatment was studied in 15 cancer patients who failed IL-2 treatment. OKT3 was given as a 2-h intravenous infusion. Doses of 50, 100, 200 and 400 micrograms OKT3 were studied. Within 24 h, subcutaneous IL-2 was started 5 days/week for 4 weeks, at a dose of 9-18 x 10(6) U daily. Maximum tolerated dose was 400 micrograms OKT3 with neurotoxicity as dose-limiting toxicity. Toxicity of subcutaneous IL-2 was acceptable. At the maximum tolerated dose, 9 patients with renal cell carcinoma with measurable disease were treated in a phase II setting. 8 patients were evaluable for response. 4 patients had stable disease and 4 had progressive disease. An increase of activated lymphocyte subpopulations could not be found, although OKT3 was detectable on lymphocytes in vivo. Only if laboratory studies shed light on methods of improving immunostimulating effects of OKT3 will further clinical studies be warranted.

Adult↗
PubMed1993

Tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 plasma levels in neonatal sepsis.

Tumor necrosis factor-alpha, IL-1 beta, and IL-6 are thought to be involved in the pathogenesis of sepsis with gram-negative bacteria. We studied these cytokines during neonatal sepsis with mainly gram-positive bacteria. Ten newborns with clinical sepsis and 22 healthy controls were enrolled in the study. TNF alpha plasma levels proved to be increased in the newborns with sepsis up to 560 +/- 234 pg/mL (ng/L) versus 36 +/- 4 pg/mL (ng/L) in the control group (p < 0.005), whereas IL-6 plasma levels in newborns with sepsis were 79.700 +/- 37.500 pg/mL (ng/L) versus 55 +/- 28 pg/mL (ng/L) in the control group (p < 0.01). The IL-1 beta plasma levels were only slightly elevated in the group newborns with sepsis [up to 18 +/- 5 pg/mL (ng/L) versus 7 +/- 1 pg/mL (ng/L) in the control group (p < 0.01)]. After the start of therapy with antibiotics, both TNF alpha and IL-6 plasma levels decreased concomitantly with the improvement of the clinical situation within 2 d. These data confirm the abundant presence of TNF alpha and IL-6 during neonatal sepsis, whereas IL-1 beta appeared to be present in small amounts only. Nevertheless, the IL-1 beta but not the TNF alpha plasma level appeared to correlate inversely with the decrease in diastolic tension as standardized according to birth weight (R = 0.66, p = 0.04). TNF alpha, IL-1 beta, and IL-6 were not correlated with any febrile response in the group with sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteremia↗