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Biomedical subjects

A Schweizer

Publications and source records attributed to A Schweizer.

At least 91 records · Page 5Linked to original sources
PubMed1988

Comparison between a low molecular weight and standard heparin for anticoagulation during extracorporeal CO2 removal in the dog.

Anticoagulant properties towards an artificial surface of a chemically depolymerized low molecular weight heparin (LMWH) have been compared to those of a standard heparin (SH). The experimental model consisted in a seven hours extracorporeal veno-venous bypass for CO2 removal (EC-CO2R) using a membrane lung. Four animals received 150 anti-FXa U/kg followed by 40 anti-FXa U/kg/h of LMWH or 300 IU/kg followed by 100 IU/kg/h of SH. Mean Factor Xa inhibition was 49% in LMWH group and 28.5% in SH group. Mean Factor IIa inhibition was 31% and 49% respectively. After three hours of bypass fibrin deposition occurred in the reservoir in three out of four dogs receiving LMWH while none was observed under SH. No statistically significant difference between the two groups was found for any of the coagulation parameters tested (fibrinogen, factor V, antithrombin III, plasminogen, alpha 2-antiplasmin, platelet counts). At the end of bypass 5000 U protamine abolished both anti-FXa and anti-FIIa activities in the SH group but failed to neutralize more than half of the anti-FXa activity in the LMWH group. These results suggest that high anti-FIIa activities are required to prevent fibrin formation induced by artificial surfaces and that equivalent amounts of anti-FXa activities are ineffective for this purpose. In addition the use of LMWH may raise problems when emergency neutralization procedures are required.

Animals↗
PubMed1988

Interleukin-1 enhances pain reflexes. Mediation through increased prostaglandin E2 levels.

Interleukin-1 (IL-1) has been shown to induce inflammatory reactions in part through increased prostaglandin production. Prostaglandins of the E- and I-type sensitize nociceptors in peripheral tissues. We have therefore investigated the effect of IL-1 perfusion in the isolated rabbit ear, a model which allows the assessment of peripheral pain. Natural IL-1 from human monocytes, IL-1 from glioblastoma cells as well as recombinant IL-1 alpha or beta, increased the pain reflex induced by acetylcholine in a concentration dependent manner. The PGE2 levels were measured in the perfusate and were found to be enhanced more than 10-fold after the infusion of IL-1 alpha or IL-1 beta. This effect was paralleled by the enhanced pain reflexes and persisted for at least one hour after cessation of the IL-1 perfusion. Both the increased pain reflexes as well as the enhanced PGE2 levels were abolished by addition of the cyclooxygenase inhibitor diclofenac-Na (Voltaren) to the perfusion fluid. These results show that besides the numerous known physiological functions of IL-1, it may also play a role in peripheral pain sensations.

Animals↗
PubMed1988

Physiological profile during venovenous perfusion in dogs using a polypropylene membrane lung with secondary flows.

Venovenous perfusion has been conducted in 12 healthy dogs to examine carbon dioxide (CO2) transfer and haemocompatibility over 9 h during total extracorporeal CO2 removal using a microporous polypropylene membrane lung with secondary flows in the blood channel. The anaesthetized animals were maintained normocapnic by including CO2 in the inspired gases. The CO2 removal was achieved using 0.631 m2 of active membrane, at a pulsatile Reynolds number of 50, and a CO2 extraction from blood of 17.8 ml (STP) dl-1. Gas exchange remained constant during the perfusions. Several aspects of our results suggest that the haemocompatibility of a system of the kind used here is at least as favourable as that of a steady flow device using a continuous silicone rubber membrane of equivalent gas transfer capability.

Animals↗
PubMed1988

Identification, by a monoclonal antibody, of a 53-kD protein associated with a tubulo-vesicular compartment at the cis-side of the Golgi apparatus.

Purified Golgi membranes of the human intestinal adenocarcinoma cell line Caco-2 were used as an antigen to produce a monoclonal antibody, G1/93, which specifically labels a tubulovesicular compartment near the cis side of the Golgi apparatus, including the first cis-cisterna itself, as visualized by single and double immunoelectron microscopy with antibodies against galactosyltransferase. The antigen recognized by G1/93 was identified as a protein with a subunit size of 53 kD. Pulse-chase experiments revealed that the 53-kD protein dimerizes immediately after synthesis followed by formation of oligomers of approximately 310 kD, probably homohexamers. The protein has a transmembrane topology with only a short cytoplasmic segment as assessed by protease protection experiments. Glycosidase digestion studies indicated that the protein is probably not glycosylated. The unique subcellular distribution of the G1/93 antigen in close vicinity to the cis-Golgi is in line with the notion that this protein may delineate the biosynthetic transport pathway from the endoplasmic reticulum to the Golgi apparatus. Moreover, G1/93 is a useful marker to identify the cis side of the Golgi apparatus in a variety of human cells.

Antibodies, Monoclonal↗
PubMed1988

Sequence and transcriptional start site of the Pseudomonas aeruginosa outer membrane porin protein F gene.

Porin F is one of the major proteins of the outer membrane of Pseudomonas aeruginosa. It forms water-filled pores of variable size. Porin F is a candidate for a vaccine against P. aeruginosa because it antigenically cross-reacts in all serotype strains of the International Antigenic Typing Scheme. We have isolated the gene for porin F from a lambda EMBL3 bacteriophage library by using oligodeoxynucleotide hybridization probes and have determined its nucleotide sequence. Different peptide sequences obtained from isolated porin F confirmed the deduced protein sequence. The mature protein consists of 326 amino acid residues and has a molecular weight of 35,250. The precursor contains an N-terminal signal peptide of 24 amino acid residues. S1 protection and primer extension experiments, together with Northern (RNA) blots, indicate that the mRNA coding for porin F is monocistronic with short untranslated regions of about 58 bases at the 5' end and about 47 bases at the 3' end. The sequences in the -10 and -35 regions upstream of the transcriptional start site are closely related to the Escherichia coli promoter consensus sequences, which explains why the porin F gene is expressed in E. coli under the control of its own promoter. The amino acid sequence of porin F is not homologous to the different E. coli porins OmpF, OmpC, LamB, and PhoE. On the other hand, a highly homologous region of 30 amino acids between the OmpA proteins of different enteric bacteria and porin F of P. aeruginosa was detected. The core region of the homology to E. coli OmpA had 11 of 12 amino acid residues in common.

Amino Acid Sequence↗
PubMed1988

A new metabolite of diclofenac sodium in human plasma.

1. Among the phenolic metabolites of diclofenac in human plasma, an unknown compound (metabolite VI) was detected by h.p.l.c. and g.c. methods. This was also found in baboon plasma. 2. Metabolite VI was identified as 3'-hydroxy-4'-methoxy diclofenac by mass and n.m.r. spectroscopic analysis. Comparison with synthetic reference compound confirmed its structure. 3. In plasma, metabolite VI persists much longer than do unchanged diclofenac and the other phenolic metabolites. In urine, metabolite VI and its conjugates are excreted in trace amounts only. 4. A synthetic sample of metabolite VI was shown to be virtually inactive in animal models of inflammation and pain.

Adult↗
PubMed1987

A sulphonamido-indanone derivative CGP 28237 (ZK 34228), a novel non-steroidal anti-inflammatory agent without gastro-intestinal ulcerogenicity in rats.

CGP 28237 (5-methylsulphonylamino-6-phenoxy-1-indanone) belongs to a series of structurally novel indanones. The compound is a weak acid (pK = 6.98), but it does not contain a carboxylic group. CGP 28237 exhibits potent anti-inflammatory activity in developing and established adjuvant arthritis in rats (ED40 approximately 0.5 mg/kg p.o.) and good activity in carrageenin oedema (ED40 approximately 3 mg/kg p.o.). It inhibits yeast-induced fever in rats with ED50 values of 1, 2 and 10 mg/kg p.o. at 1, 3 and 5 hours after drug administration. The antinociceptive activity in mice (phenyl-p-benzoquinone writhing) and rats (acetic-acid writhing) is weak. CGP 28237 has been shown to be non-ulcerogenic in rats under acute and chronic test conditions: it does not cause mucosal lesions in the stomach at 2 X 400 mg/kg p.o., it does not enhance gastro-intestinal blood loss during 10 days' oral treatment with 400 mg/kg p.o., and it did not induce gastro-intestinal lesions in a 4-week toxicity study up to 1000 mg/kg p.o. Although CGP 28237 is not a cyclooxygenase inhibitor in bovine seminal vesicle microsomes, it inhibits prostaglandin synthesis in zymosan-stimulated murine macrophages (IC50 approximately 3 X 10(-6) mol/l) and protects rabbits against arachidonic acid-induced lung embolism with 10 mg/kg p.o. CGP 28237 may represent a novel anti-inflammatory drug with excellent gastro-intestinal tolerability.

Animals↗
PubMed1986

Pharmacology of diclofenac sodium.

Diclofenac sodium is the active ingredient in Voltaren, a nonsteroidal anti-inflammatory drug designed by selection of appropriate physicochemical and steric properties. Its pharmacologic activity, specifically its effects in acute and subchronic inflammation, and its analgesic activity have been assessed in animal models. The tolerability of the compound as judged by several parameters (i.e., ratio between the acute lethal dose or the dose inducing gastrointestinal blood loss and the desired pharmacologic activity) is favorable in comparison with other nonsteroidal anti-inflammatory drugs. Diclofenac sodium acts by potent cyclo-oxygenase inhibition, reduction of arachidonic acid release, and enhancement of arachidonic acid uptake. It thereby results in a dual inhibitory effect on both the cyclo-oxygenase and lipoxygenase pathways.

Analgesics↗
PubMed1985

Differentiation of peripheral and central effects of analgesic drugs.

The nonsteroidal antiphlogistic and antinociceptive agents acetylsalicylic acid, diclofenac-Na and paracetamol, and the centrally acting analgesic morphine, were tested in the isolated perfused rabbit ear. This model allows for the distinction between centrally and peripherally acting analgesic drugs. It was found that local acetylsalicylic acid, diclofenac-Na and paracetamol inhibited the pain reflexes (blood pressure change, "head-flick" response) induced by bradykinin, whereas local morphine proved to be inactive. In contrast, after systemic administration, only morphine, but not acetylsalicylic acid, diclofenac-Na and paracetamol, was active in a therapeutic dose range. Thus, the isolated rabbit ear model is useful for differentiating peripheral from central sites of action of an analgesic agent.

Acetaminophen↗
PubMed1984

Leukotrienes reduce nociceptive responses to bradykinin.

The biotransformation of arachidonic acid leads to two important groups of inflammatory mediators, the leukotrienes and the prostaglandins. Hyperalgesic effects have been demonstrated for prostaglandins in a variety of animal models but the effects of leukotrienes on inflammatory pain are less well documented. Using the isolated rabbit ear model of algesia we have shown that perfusion of the ear with the leukotrienes B4, C4 and D4 (10(-8)-10(-7) M) causes a reversible, dose- and time-dependent reduction of the reflex fall in systemic blood pressure and the "head flick" response induced by injection of bradykinin (400 ng), without affecting similar responses induced by the neurotransmitter acetylcholine. The antagonistic effect of leukotrienes on the algesic action of bradykinin could be reversed by the leukotriene antagonist FPL55712 (2 micrograms/ml). This result implies that the leukotrienes may have a desensitizing effect on the nociceptor during an inflammatory response in contrast to the pain threshold-lowering action of the E- and I-type prostaglandins.

Acetylcholine↗
PubMed1984

Determination of pirprofen in biological material by gas-liquid chromatography with nitrogen-specific and electron-capture detection.

Pirprofen, 2-[3-chloro-4-(3- pyrrolin -1-yl)phenyl]propionic acid, is an analgesic and anti-inflammatory agent. Most of the pirprofen is present in plasma in the unchanged form (80-90%), the remainder in the form of the pyrrole derivative. However, pyrrole is also formed during sample manipulation by oxidation of pirprofen. Thus, a method based on conversion of pirprofen to pyrrole by oxidation with 2,3- dicyano -5,6- dichlorobenzoquinone and subsequent measurement of the total pyrrole concentration was developed. The method is based on the introduction of an internal standard, extraction and esterification followed by oxidation. The methyl ester of the pyrrole is then determined by gas-liquid chromatography. A nitrogen-specific detector is generally used. However, for small sample sizes (0.1 ml of plasma), an electron-capture detector may be utilized. With this detector measurements of concentrations as low as 0.02 nmol/g (5 ng/g) are still possible. The kinetics of the degradation of pirprofen to its pyrrole derivative were investigated. Plasma levels of pirprofen after a single oral dose of 400 mg in a healthy volunteer were measured by a method described previously as well as by the new method.

Adult↗
PubMed1984

Sulfonyliminoimidazolidines, a new class of oral hypoglycemic agents. 4. Toxicity and general pharmacology of 1-[p-[2-(crotonylamino)-ethyl]-phenylsulfonyl]-3-cyclohexy l-2-imino- imidazolidine (CGP 11 112).

Results of a first segment of toxicity tests and general pharmacological investigations with 1-[p-[2-(crotonylamino)-ethyl]-phenylsulfonyl]-3-cyclohexyl- 2- iminoimidazolidine (CGP 11 112), a potent new oral hypoglycemic agent, are reported. The acute LD50 in rats was 600 mg/kg p.o. and 25 mg/kg i.v. In a range finding study doses of 60 mg/kg p.o. and 10 mg/kg i.p., administered daily for 10 days, were tolerated without symptoms in rats, and 30 mg/kg p.o. produced no unequivocal toxic effects in dogs. Slight and transient increases of blood pressure were observed in anaesthetized cats at doses of 0.3 mg/kg i.v. and above. 3 mg/kg i.v. (1/10 LD) caused a transient blood pressure decrease. Heart rate, tidal volume and blood pressure effects of epinephrine (adrenaline), norepinephrine (noradrenaline) and acetylcholine were not significantly influenced in a dose range from 0.01 to 1.0 mg/kg i.v. In isolated organ segments, CGP 11 112 produced only unspecific effects at high concentrations. No intrinsic activity, but antagonism against BaCl2-induced contractions were observed in isolated guinea-pig ileum (one third papaverine hydrochloride). Rate and force of contraction of isolated guinea-pig atria were not affected up to 2.4 mumol/l; higher concentrations were cardiodepressant. In rats, CGP 11 112 increased the excretion of urine, sodium and chloride, but not potassium, dose-dependently (range 10-100 mg/kg). Similar effects observed in dogs suggest that the compound may affect fluid and electrolyte balance at high doses. Moderate antiphlogistic activity (ED40 10-40 mg/kg) was observed in the carrageenin-induced rat paw oedema.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗