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Biomedical subjects

W Binder

Publications and source records attributed to W Binder.

At least 19 recordsLinked to original sources
PubMed2001

Peripheral opioid analgesia.

Major recent findings in peripheral opioid analgesia include the relative lack of tolerance under inflammatory conditions, tetrapeptides as novel peripherally restricted compounds, the potent anti-inflammatory activity of mu and kappa agonists and the identification of selectins as important molecules governing the homing of opioid cells to injured tissue. Clinical studies have now moved into the field of chronic arthritic pain, a problem of major relevance and prevalence.

Analgesics, Opioid↗
PubMed2001

Analgesic and antiinflammatory effects of two novel kappa-opioid peptides.

BACKGROUND: This study investigates two new kappa-agonist tetrapeptides, FE 200665 and FE 200666, with high peripheral selectivity as a result of poor central nervous system penetration. METHODS: Four days after administration of Freund adjuvant into the hind paw of male Wistar rats, antinociceptive effects of intraplantar and subcutaneous injection of FE 200665 and FE 200666 were measured by paw pressure algesiometry and compared with the kappa-agonist U-69,593. Peripheral and kappa-receptor selectivity was assessed by the antagonists naloxone methiodide (NLXM) and nor-binaltorphimine, respectively. Antiinflammatory effects were evaluated by paw volume plethysmometry and histologic score. RESULTS: Similar to intraplantar U-69,593, intraplantar FE 200665 (3-100 microg) and FE 200666 (1-30 microg) resulted in significant and dose-related increases of paw pressure thresholds. Higher doses of FE 200665 (0.2-20 mg) and FE 200666 (0.06-6 mg) were required by subcutaneous route to produce similar antinociceptive responses, supporting a peripheral site of action. nor-Binaltorphimine dose-dependently antagonized this effect, implying kappa-opioid selectivity. Analgesic effects of subcutaneous FE 200665 and FE 200666 were abolished by intraplantar nor-binaltorphimine, and both subcutaneous and intraplantar effects were dose-dependently antagonized by subcutaneous NLXM, further demonstrating a peripheral site of action. One to 6 days after Freund adjuvant inoculation, single and repeated intraplantar injections of FE 200665, FE 200666, and U-69,593 significantly reduced paw volume and histologic scores. Both changes were reversed by intraplantar nor-binaltorphimine and subcutaneous NLXM. CONCLUSION: FE 200665 is a peripherally selective kappa-agonist with potent analgesic and antiinflammatory properties that may lead to improved analgesic-antiinflammatory therapy compared with centrally acting opioids or standard nonsteroidal antiinflammatory drugs.

Analgesics, Opioid↗
PubMed2000

Effect of gender on anti-inflammatory and analgesic actions of two kappa-opioids.

The higher incidence of inflammatory and painful disorders in women and recent reports that have emphasized the importance of gender in nociceptive sensitivity and responsiveness to analgesics prompted us to investigate gender as a factor in the variability in response to opioids. We studied the anti-inflammatory and antinociceptive effects of two kappa-opioid agonists in adjuvant-induced arthritis, one that acts both peripherally and centrally (PNU50488H; 20 mg/kg/day), the other which is peripherally selective (asimadoline; 5 mg/kg/day). Both drugs had equally powerful anti-inflammatory effects in both male and female rats (reducing measures by 60-80%). In contrast, there were gender-based heterogeneities in their analgesic actions, contingent on the method of stimulation (mechanical or thermal); males were insensitive to the analgesic effects of asimadoline with thermal but not mechanical nociceptive stimuli. We also sought evidence for gender influences on the joint content of Substance P (SP), a peptide suggested to have a role in producing inflammation and found that levels were higher in the untreated arthritic females, although there were no gender differences in disease sensitivity or nociception in arthritic animals receiving no drugs. Paradoxically, both drugs elevated SP concentrations in the joints, perhaps as a consequence of an action of kappa-opioids to suppress SP release from peripheral nerves, but the gender differences remained. Further experiments are required to determine exact mechanisms responsible for the gender distinction in analgesic response to kappa-opioids that may involve differential activation of primary afferents.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1999

Involvement of substance P in the anti-inflammatory effects of the peripherally selective kappa-opioid asimadoline and the NK1 antagonist GR205171.

We have previously shown that kappa-opioids have antiarthritic properties. In this study, using two differently acting drugs (the peripherally selective kappa-agonist, asimadoline, and the NK1-antagonist, GR205171), we have examined possible roles of the neuropeptide substance P (SP) in the pathogenesis and maintenance of experimental arthritis in rats. The anti-inflammatory actions and the time dependence of these drugs were compared, and concentrations of SP determined in joint tissue. In untreated animals, SP levels in ankle joint tissue increased late in the disease (by day 21) but substantially lagged behind development of clinical disease. Prolonged (days 1-21 or days 12-18) but not early, short-term (days 1-3) treatment with the NK1-antagonist GR205171 (1 mg/kg/day i.p.) significantly attenuated joint damage; SP levels showed multiphasic dose dependence over the 21-day treatment. The data suggest that GR205171 antagonizes the action of SP by presynaptic as well as postsynaptic mechanisms. Treatment with asimadoline (5 mg/kg/day i.p. ) produced marked (and sustained) attenuation of the disease with all three time regimes. The effect of asimadoline on SP levels was time dependent: reduction of SP content after 3 days but an increase after 12 or 21 days treatment, paradoxically with clinical improvement in each case. Drug-induced changes in SP content could follow from changed release or synthesis from either neural or immune cells. The results suggest that both drugs have potential therapeutic value at different stages of inflammatory joint disease.

Acetamides↗
PubMed1998

Stimulation of phospholipase C-beta2 by the Rho GTPases Cdc42Hs and Rac1.

Neutrophils contain a soluble guanine-nucleotidebinding protein, made up of two components with molecular masses of 23 and 26 kDa, that mediates stimulation of phospholipase C-beta2 (PLCbeta2). We have identified the two components of the stimulatory heterodimer by amino acid sequencing as a Rho GTPase and the Rho guanine nucleotide dissociation inhibitor LyGDI. Using recombinant Rho GTPases and LyGDI, we demonstrate that PLCbeta2 is stimulated by guanosine 5'-O-(3-thiotriphosphate) (GTP[S])-activated Cdc42HsxLyGDI, but not by RhoAxLyGDI. Stimulation of PLCbeta2, which was also observed for GTP[S]-activated recombinant Rac1, was independent of LyGDI, but required C-terminal processing of Cdc42Hs/Rac1. Cdc42Hs/Rac1 also stimulated PLCbeta2 in a system made up of purified recombinant proteins, suggesting that this function is mediated by direct protein-protein interaction. The Cdc42Hs mutants F37A and Y40C failed to stimulate PLCbeta2, indicating that the Cdc42Hs effector site is involved in this interaction. The results identify PLCbeta2 as a novel effector of the Rho GTPases Cdc42Hs and Rac1, and as the first mammalian effector directly regulated by both heterotrimeric and low-molecular-mass GTP-binding proteins.

Amino Acid Sequence↗
PubMed1998

Effect of the peripherally selective kappa-opioid agonist, asimadoline, on adjuvant arthritis.

1. Opioids, though widely used as analgesics, have not been seriously considered as therapy for rheumatoid arthritis. The present study evaluated the dose-effect and time-dependence relationships of a new peripherally selective kappa agonist, asimadoline, in rats with adjuvant arthritis. 2. The arthritis was assessed by a pooled severity index combining the comprehensive criteria of oedema, radiography and histological changes, in the hind limbs. Asimadoline was extremely effective in attenuating joint damage (by up to 80%) when administered parenterally (0.5 to 10 mg kg(-1) day(-1), i.p.) throughout the disease or during its early phase; treatment was less successful if confined to the latter stages. Ten fold higher doses were effective orally. 3. Equimolar doses of a peripherally-selective antagonist, naloxone methiodide, and the kappa-selective antagonist, MR2266, fully reversed the peripheral anti-arthritic effects of asimadoline (5 mg kg(-1) day(-1)), indicating that asimadoline acts through peripheral kappa-opioid receptors. However, an equivalent dose of MR2266 did not fully reverse the anti-arthritic effects of the highest dose of asimadoline (40 mg kg(-1) day(-1)), suggesting a loss of kappa-selectivity at this dose. 4. Asimadoline also exhibited analgesic effects (mechanical nociceptive thresholds) in arthritic but not non-arthritic rats, indicating that inflammation is necessary for asimadoline-induced analgesia. 5. These data confirm our previous findings that kappa-opioids possess anti-arthritic properties and that these effects are mediated via peripheral kappa-receptors. The present results are new in showing that the peripherally acting kappa-opioid agonist, asimadoline, is a potent anti-arthritic agent. Such novel drugs, essentially lacking central side effects, herald new treatments for rheumatoid arthritis.

Acetamides↗
PubMed1996

Effect of mu-opioids morphine and buprenorphine on the development of adjuvant arthritis in rats.

OBJECTIVE AND DESIGN: On the basis that endogenous opioids play a role in the physiological response to inflammation, this study tests the anti-arthritic effects of a mu-opioid agonist, morphine and the partial mu-agonist, buprenorphine. MATERIAL: Male Lewis rats were used. TREATMENT: Rats were inoculated subcutaneously with 0.05 ml of Freund's complete adjuvant (5 mg/ml) into the right hind paw to produce adjuvant arthritis. Morphine (either 10 to 60 mg/kg/day s.c. bolus or 60 mg/kg/day s.c. infusion) and buprenorphine (0.65 +/- 0.06 mg/kg/day, orally), respectively, were administered for 3 days during the primary inflammatory phase of adjuvant arthritis. METHODS: The progression of adjuvant arthritis was monitored every three days by body weight change and hind limb oedema (ipsilateral and contralateral). On day 21 the animals were sacrificed and histology and radiography of the contralateral limb were performed. In rats receiving Freund's adjuvant and no drug treatment, the incidence of arthritis was 89%. Effect was expressed as the pooled severity index (PSI) derived from the arithmetic average of the volume, histology and radiography scores in the contralateral hind limb. RESULTS: Buprenorphine had no effect on experimental arthritis (PSI control vs treated: 242 +/- 28 vs 253 +/- 28%). In contrast, morphine by subcutaneous injection twice daily (10 to 60 mg/kg/day) but not by subcutaneous infusion (60 mg/kg/day) was found to attenuate the progression of adjuvant arthritis in a dose-dependent manner. This indicates that the anti-arthritic effects of morphine are opioid receptor mediated (ED50, 58 +/- 9 mg/kg) and suggests that the local concentration reached effective levels only after subcutaneous injection. It is also possible that the high doses of morphine were anti-inflammatory through effects at the kappa receptor. However, these high doses of morphine produced death in one third of the rats, the calculated lethal dose (LD50, 63 +/- 2 mg/kg) being close to the effective dose. CONCLUSION: Anti-arthritic effects of morphine are opioid receptor mediated but morphine use for this indication is restricted by its adverse effects.

Analgesics, Opioid↗
PubMed1994

Botulinum toxin A for hyperkinetic facial lines: results of a double-blind, placebo-controlled study.

Previous work on patients with muscular dystonia has shown that small intramuscular doses of botulinum toxin A eliminated hyperkinetic facial lines for approximately 6 months. The purpose of this study was to determine the efficacy of botulinum toxin A injections in eliminating facial wrinkles in aesthetic surgery patients who do not have muscular dystonia. Eleven healthy subjects were studied in a double-blind fashion. On both sides of the face, 0.2 cc of either normal saline or botulinum toxin A was injected into the forehead or into the periorbital wrinkles (crow's feet). Documentation of results was made by photographs taken of the patients during repose and during facial animation before and after injection. Assessment of facial wrinkles was done from a grading system in which the patient and the facial plastic surgeon were asked to judge the severity of the wrinkles on a scale from 0 to 3, with 0 reflecting no facial wrinkles and 3 reflecting severe facial wrinkling. Nine of 11 subjects injected with botulinum toxin A noted a significant improvement in the severity of their facial wrinkles in comparison with the side of the face injected with saline, with a rating improvement of 2 points. Two of 11 subjects noted a moderate improvement, with a rating improvement of 1 point. No patient injected with saline reported an improvement in the severity of the facial wrinkles on the control side. There were no serious complications. Botulinum toxin A is an efficacious method of nonsurgically eliminating facial wrinkles and may play a role in the cosmetic enhancement of the aging face.

Adult↗
PubMed1993

[Can administration of trasylol in reduced Hammersmith dosage with simultaneous transfusion of autologous blood meet the requirements of open heart surgery?].

PROBLEM: The general positive effect of the proteinase inhibitor trasylol on blood loss and transfusion demand in cardiac surgery has been demonstrated in several placebo-controlled studies. Given the possibility of cardiac and renal side effects associated with a high dose of trasylol (Hammersmith dosage: 6 x 10(6) kallikrein inactivator units KIU), the question of a dose reduction was raised. METHODS: Being designed as a randomized double-blind comparative group study, the investigation included 120 patients with elective primary cardiac surgery from November 1990 to April 1992. One characteristic aspect of this study was the combined administration of trasylol and autologous blood transfusions. To compare the efficacy and safety of different doses of trasylol, two groups, each with 60 patients, were created: the former with the full Hammersmith dose (high dose group = HD group), the latter with half of the Hammersmith dose (los dose group = LD group). A placebo group had to be excluded for ethical reasons. RESULTS: The trasylol plasma levels showed a good dose correlation for the complete interval. The intra-operative bleeding tendency, as judged by the surgeons in charge, did not show any statistical significant difference between the HD group and the LD group. As to the post-operative blood loss via thoracic drainage, the early collection periods did not show any difference between both study groups. Starting at 6 hours post-operatively, the drainage losses showed a tendency towards lower volumes in the HD group. This difference was statistically significant for the time period "6-12 hours post-operatively". The analysis of the post-operative complications did not show any difference. SUMMARY: In this study with a high percentage of autologous blood transfusions, a lower dose of trasylol seemed to be nearly as effective as a full Hammersmith dose. However, such a reduced dose did not demonstrate any advantage regarding the complication rate in comparison with the conventional high dose.

Aprotinin↗
PubMed1992

Results and implications of high-resolution surface dosimetry of ruthenium-106 eye applicators.

The dosimetry of 106Ru/106Rh beta-emitting eye applicators is still inadequate. Manufacturer's specifications of absolute dose rates are loaded with a +/- 30% error, and the relative distribution of activity on the surface is measured on a few points only, using a 3-mm plastic scintillation probe. While reducing the absolute error of dose rate measurements to +/- 15% by a method published earlier, we now present a phantom using small thermoluminescent dosimetry crystals for refined assessment of its distribution over the surface. Evaluation of two applicators revealed a 50% increase in activity in the midperiphery in one and a steep falloff of activity 1 mm within the margin of both specimens. The method and findings are demonstrated in detail and compared to those reported by other authors.

Brachytherapy↗
PubMed1990

[Brachytherapy using Ru-106 applicators in ophthalmology].

Two Ru-106 applicators of the type CCB as manufactured by the "Zentralinstitut für Isotopen- und Strahlenforschung" (Berlin, GDR) were investigated. The homogeneity of the relative dose distribution at the surface of the applicators was determined. For the evaluation of the data extremely small TLD crystals (2 x 1 x 1 mm) had to be manufactured as well as an almost tissue equivalent acrylic eye phantom. In order to assure reproducibility of the applicator positioning, the plaque suture eyelets had to be placed on locating pins. 120 points of measurements located within the active plaque area of 20 mm diameter were evaluated. The results show that the area to be used in tumor treatment is about 20 to 25% less than expected. One plaque shows a considerable inhomogeneity with respect to dose distribution (up to 40%). A modified eye phantom was used for the determination of the central axis depth dose distribution.

Brachytherapy↗
PubMed1990

[Interstitial radiotherapy of breast cancer. Preliminary report of a prospective study of 165 cases subjected to breast-conserving treatment].

UNLABELLED: The results of a prospective study on breast conserving therapy in early stage breast cancer are presented. From January 1983 to June 1987 165 patients were treated by a standardized therapy-protocol. The criteria for entering the trial were stage T1 to T2 and N0 to N1. Surgical breast conservation was achieved by segmental resection in 148 cases and by tumorectomy in 17 cases. 160 patients underwent axillary lymph node dissection. Obligatory 45 to 50 Gy were delivered percutaneously to the operated breast and optional 50 Gy to the regional lymph nodes (axillary lymph node involvement greater than 3 nodes). In addition, the area of the primary breast lesion itself was boosted interstitially by an Iridium 192 implant (LDR-technique: 15 to 20 Gy, HDR-technique: 10 to 12 Gy). RESULTS: Progression of disease in 10% of the patients (16/165), local recurrence rate in the operated breast: 2% (3/165), axillary recurrence: 0.5% (1/165). 5% of the patients (8/165) died from metastatic disease, two patients died free of recurrence for reasons unrelated to cancer, two other patients died on unknown reasons. Because of the low number of local recurrences and the observation period of 32 months, no statistically contribution on high risk factors for local failure could be found.

Adult↗
PubMed1989

Assessment of echographic regression criteria in ruthenium-irradiated melanoma.

Steady flattening of the tumor, increasing reflectivity and decreasing vascularity are echographic signs of successful irradiation treatment. The specific example of an irradiated choroidal melanoma shows that the absence of echographic changes by no means excludes tumor destruction. Because of a dense vitreous body hemorrhage, the melanoma could only be evaluated echographically. Since the echogram lacked evidence of regression, the tumor was locally resected 5 months later. Histology, however, revealed an amorphous mass of dead tissue pervaded by intact vessels. Apparently a successfully irradiated melanoma may generate an echo typical of vital melanoma tissue. The authors therefore draw the conclusion that only a steady tumor growth, as substantiated by an echogram, may be considered an unambiguous sign of tumor vitality.

Choroid Neoplasms↗
PubMed1988

Radiotherapy of metastatic renal cell carcinoma.

Modern oncological treatment of metastatic renal cell carcinoma may have different goals: first of all, improvement of survival rates; secondly, elimination of symptoms like pain from osseous lesions or disorders of central nervous system functions. Chemotherapy or radiotherapy or the combination of both should improve life quality and be tolerable to the patient. Close interdisciplinary contacts of medical and radiological oncologists are therefore necessary. Radiotherapy should be carried out under conditions of high-voltage energy and modern treatment planning to concentrate and limit the irradiation volume as much as possible. Split-course technique and radiation as interval treatment between chemotherapy courses seem to be optimal. Our clinical results indicate that the reported radioresistance of renal cell carcinoma might result from radiobiological and methodological misinterpretations.

Bone Neoplasms↗
PubMed1987

Technique of ruthenium-106 application in the treatment of conjunctival melanoma.

In 1966 Lommatzsch has introduced the ruthenium-106 radiation therapy in the treatment of the choroidal melanoma. He reported on good results with a less rate of ocular side effects in compare to the different forms of conventional radiation therapy modalities. It seemed useful to utilize the advantages of ruthenium-106 therapy also for the treatment of the conjunctival melanoma. The technique of the ruthenium-106 irradiation of conjunctival melanoma is described and the first clinical results are reported.

Aged↗
PubMed1985

[A procedure for the determination of dose performance of radioactive eye applicators (106-Ru/106-Rh) and their significance for indications and treatment in malignant choroid melanomas].

Choroidal melanomas occasionally respond very differently to irradiation by ruthenium beta-ray applicators. In order to clarify the role of the radiation parameters on the one hand and the tumor properties on the other, more precise data on the actual surface does rate than those furnished by the supplier are indispensable. With the aid of a measuring method based on the principle of thermoluminescence, the deviation was halved a +/- 15%. The measuring instrument is described, and its impact pact on therapeutic safety and indication limits is discussed.

Choroid Neoplasms↗