Passiflora and lime-blossoms: motility effects after inhalation of the essential oils and of some of the main constituents in animal experiment.
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Administration, Inhalation↗
Biomedical subjects
W Jäger
Publications and source records attributed to W Jäger.
Expression of the Bacillus subtilis sacB gene leads to sucrose sensitivity in the gram-positive bacterium Corynebacterium glutamicum but not in Streptomyces lividans.
The expression of the structural gene (sacB) encoding Bacillus subtilis levansucrase in two gram-positive soil bacteria, Corynebacterium glutamicum ATCC 13032 and Streptomyces lividans 1326, was investigated. sacB expression in the presence of sucrose is lethal to C. glutamicum but not to S. lividans. While S. lividans secretes levansucrase into the medium, we could show that the enzyme is retained by C. glutamicum cells. Our results imply that the sacB gene can be used as a positive selection system in coryneform bacteria.
Bacillus subtilis↗
[Effects of valerian root oil, borneol, isoborneol, bornyl acetate and isobornyl acetate on the motility of laboratory animals (mice) after inhalation].
The aromatherapeutical use of commercial valerian root oil (Chinese origin) and of pure fragrance compounds--borneol, isoborneol, bornyl acetate (main constituent of the proved valerian root oil) and isobornyl acetate--as potentially drugs with sedative effects after inhalation was investigated in an animal experiment (mice). In additional analyses the mice were treated i.p. by caffeine and distinct sedative effects were observed only by inhalation of the cited substances.
Animals↗
Influence of interferon alfa-2b with or without folinic acid on pharmacokinetics of fluorouracil.
Interferon alfa has been demonstrated to enhance the effect of fluorouracil (5-FU) on human colon cancer cell lines as well as in clinical studies. By several authors interest in focussed on the question whether the interaction between these two agents is reflected by changes of 5-FU kinetics. In the present study the pharmacokinetic behavior of 5-FU was investigated in combination with interferon alfa (IFN-alpha-2b) and further after adding the second well-established biomodulating agent folinic acid (FA). Ten patients with advanced gastrointestinal cancer received 5-FU as a weekly bolus injection of 750 mg/m2, IFN-alpha-2b 5 million units three times per week subcutaneously and FA as a short time infusion at 200 mg/m2. 5-FU plasma levels were determined by high performance liquid chromatography as a baseline measurement on day 1 before starting IFN-alpha-2b. Analysis was repeated at the second or third cycle of 5-FU administration 1 hour after the last IFN-alpha-2b injection, and finally after also adding FA immediately infused before 5-FU injection. Biomodulation of 5-FU by IFN-alpha-2b alone resulted in a significant alteration of 5-FU kinetic parameters as demonstrated by an increase of area under the curve by 80%, and of blood concentration (co) by 65%, and a decrease of total clearance at 50%. These data may partly explain the observed enhancement of antiproliferative and toxic effects of this combination. On the other hand, when FA was added to this schedule, no significant changes of 5-FU kinetics could be documented. Therefore the theoretical benefit of such a double modulation cannot be supported by our findings. Further preclinical and clinical investigations are required to define the role of a triple combination of 5-FU with IFN-alpha-2b and FA.
Aged↗
Pharmacokinetic aspects of interferon alfa-2b after intrahepatic or intraperitoneal administration.
The pharmacokinetics of interferon alfa-2b (IFN-alpha-2b) were determined following intraperitoneal (IP) infusion of escalating doses, ie, 5, 10, and 15 million units (MU) and intrahepatal-intraarterial (IA) (IA, bolus v 24 hours continuous infusion of 3 and 5 MU) administration in patients with metastatic cancer. Pharmacokinetic parameters show that bioavailability of IFN-alpha-2b after IP administration is 30 times higher for the peritoneal fluid (PF) than for peripheral blood (PB) explaining also the low incidence of side effects. The high affinity of IFN-alpha-2b to the peritoneal cavity is furthermore substantiated by the total compartment clearance, which is only about 1 1/minute for the PF in comparison to about 30 1/minute as determined for PB. IFN-alpha-2b is eliminated from the PF with a half life (t1/2) of elimination 10 to 32 hours and from the blood with t1/2 of 5 to 13 hours. After IA bolus, IFN is distributed from the blood with a t1/2 below, 2 hours, with dose-dependent serum peak concentrations (c = 47 IU for 3 MU and 145 IU for 5 MU). Twenty-four-hour infusion leads to a steady state within 4 to 6 hours and maximum concentration of 8.5 or 12.5 IU/mL, respectively. During infusion IFN alpha-2b is slowly eliminated with a t1/2 of 16 hours. The lower area under the curve levels after bolus injection may suggest a better tissue uptake of IFN-alpha-2b by the liver. Further studies on pharmacokinetics are warranted to establish exact dose recommendations for an optimal schedule using this route and mode of IFN-alpha-2b administration in mono- and combination therapies.
Female↗
Glutaraldehyde affects biocompatibility of bioprosthetic heart valves.
A marked release of glutaraldehyde from commercially available pericardial bioprosthetic heart valve (BHV) material in washing solutions was found by high performance liquid chromatography (up to 1.8 ppm of glutaraldehyde per gram of dry tissue). In vitro endothelial cell proliferation rate was impaired dose-dependently in the presence of increasing glutaraldehyde concentrations of the cultivation medium (r = 0.9; p less than 0.05). Cultivation of endothelial cells was impossible on the surface of commercially available BHV material, but successful and uninhibited when toxic glutaraldehyde ligands of the BHV material were antagonized by treatment with L-glutamic acid.
Animals↗
[The effect of the vasoconstrictor glycylpressin on the bioavailability of mitomycin C].
During an intra-arterial chemotherapy of patients with liver metastases the plasma concentration-time curves of Mitomycin C (1) after occlusion of the common hepatic artery by the vasoconstricting agent Glycylpressin (2) were investigated. Vasoconstriction by 2 leads to significantly (p less than 0.01) lower blood levels of 1 in contrast to bolus injection of 1 without 2 under identical dosage regimens. This reduction of systemic availability of about 50% leads to a corresponding higher availability for the tumor region.
Aged↗
[Pharmacokinetics of carboplatin after intraperitoneal administration].
The concentration-profile of the antineoplastic agent carboplatinum in serum and intraperitoneal-fluid (IPF) of six female patients was studied. Pharmacokinetical analysis showed a rapid distribution-phase between both compartments within the first 4h after administration (t1/2 serum = 4.4 h, t1/2 IPF = 3.3 h). Elimination half-life of carboplatinum of 20.3 h from the blood-vessel-system was significantly higher than from the intraperitoneal-compartment (t1/2 = 10.6 h). The relative bioavailability (calculated as AUC-values) was at least 6 times higher for the IPF than for serum within the first 48 h. 98% of measured amount were eliminated from both compartments within this time. The desired high IPF-levels support this route of administration.
Carboplatin↗
Investigations of animal blood samples after fragrance drug inhalation by gas chromatography/mass spectrometry with chemical ionization and selected ion monitoring.
The fragrance compounds linalool (1) and linalyl acetate (2) could be detected, identified and quantified (1: 7-9 ng ml-1; and 2: 1-2 ng ml-1 and 4-5 ng ml-1 as free linalool) in blood samples after inhalation in animal experiments (mice) by gas chromatography/mass spectrometry (GC/MS) with chemical ionization (CI) (ammonia); selected ion monitoring (SIM) mode (1: m/z 81, 137 and 154; 2: 47, 57 and 137) and GC/flame ionization detection (FID). The inhalation of these monoterpenes in concentrations of 5 mg l-1 air leads to a significant reduction of the motility of the test animals down to 30-40% with respect to the control group.
Acyclic Monoterpenes↗
[Disseminated intraperitoneal trophoblast tissue after laparoscopic treatment of extrauterine pregnancy].
We report on the atypical course of a 31-year old primigravida, who underwent conservative treatment for a tubal pregnancy. After confirmation of the diagnosis by means of laparoscopy, a linear salpingotomy and removal of the products of gestation were performed through the laparoscope. Routine measurements of the serum HCG levels postoperatively showed, after a short period of decreasing HCG levels, a new rapid increase of HCG values. At relaparoscopy, evidence for an intraperitoneal dissemination of trophoblastic tissue was found and confirmed by histology. After treatment with 20 mg methotrexate q.i.d. per os for 5 days, HCG levels returned to normal within a short time. Apart from a minor degree of an aphthosal stomatitis, the patient did not experience any major side effects from the treatment.
Adult↗
Plasma luteinizing hormone bioactivity and immunoactivity in ovariectomized rats treated with a long-acting agonist of luteinizing hormone releasing hormone.
The dose response of a luteinizing hormone releasing hormone (LHRH) agonist in rats with high endogenous gonadotrophin levels was determined. Female rats were ovariectomized and injected with 0.3 microgram (group B), 3.2 micrograms (group C), 32 micrograms (group D) and 320 micrograms (group E) of a slow-releasing microcapsule preparation of the LHRH agonist D-Trp 6-LHRH. Control ovariectomized rats (group A) remained untreated. Plasma luteinizing hormone (LH) concentrations were measured by radioimmunoassay (RIA) before the LHRH agonist injection as well as 5, 15 and 30 days thereafter. Furthermore, LH bioactivity was determined by an in vitro rat LH bioassay in order to evaluate changes in bioactivity after administration of LHRH agonist. In control rats, plasma LH concentrations increased to 4.8 +/- 1.3 ng/ml on day 5, reaching peak levels of 9.9 +/- 1 ng/ml on day 30. In contrast to the control group, those rats which received 320 micrograms of LHRH agonist did not show any increase. Rats which received intermediate doses (groups C and D) tended to maintain levels of LH halfway between group A and group E during the first 15 days of treatment. Thereafter LH concentrations were similar to the untreated control group. The course of the LH concentrations during treatment measured by bioassay (BA) showed a similar pattern to the LH concentrations measured by RIA. The BA/RIA ratio was similar in all groups.
Animals↗
Determination of pyrimidine deoxynucleoside triphosphates in leukaemia cell extracts containing 1-beta-D-arabinofuranosylcytosine triphosphate.
Deoxynucleoside 5'-triphosphates (dNTPs) can be determined in cell extracts by high performance liquid chromatography after prior selective degradation of ribonucleoside 5'-triphosphates with sodium periodate and methylamine. When the method is used for the evaluation of deoxynucleoside triphosphates in 1-beta-D-arabinofuranosylcytosine triphosphate (ara-CTP)-containing cell extracts, an additional peak coeluting with thymidine triphosphate (dTTP) is observed. This peak is due to the formation of a carboxylic acid derivative of ara-CTP by periodate oxidation, and it can lead to considerable overestimation of dTTP. Formation of this peak can be avoided by using alkaline reaction conditions (pH 7.5) and by changing the sequence of addition of the reagents used in the periodation procedure. By employing this modified protocol, cellular dNTP and ara-CTP levels can be monitored in extracts of leukaemic blasts during cytosine arabinoside treatment in two separate HPLC runs.
Adenosine Triphosphate↗
[Modified breast cancer after care].
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Aftercare↗
[Pharmacokinetic aspects of the combination of interferon-alpha-2b and folic acid with fluorouracil].
The plasma levels of fluorouracil (5-fluorouracil, 5FU; CAS 51-21-8) after intravenous administration have been monitored without, under influence of interferon-alpha-2b (IFN) and under influence of IFN combined with folic acid (FA). IFN causes a highly significant change of the pharmacokinetic parameters of 5FU (p less than 0.001) compared to 5FU administration without IFN. The bioavailability of 5FU (compared as the AUC0-60 values) is elevated to 80%. In contrary, the combination of IFN with FA leads to a non-significant change of the 5FU pharmacokinetics, although the bioavailability is increased to 18%. The higher plasma levels of 5FU under the influence of IFN might be causes by a changed renal clearance, which is indicated by the reduction of the total plasma clearance at about 53%. The combination IFN/FA did not show a similar effect. Yet, in both cases an improvement of the tumor response and of the clinical picture could be observed.
Aged↗
[Ototoxicity of cisplatin chemotherapy in patients with ovarian cancer].
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Antineoplastic Combined Chemotherapy Protocols↗
[Prognostic importance of tumor cell detection in exudates and peritoneal lavage fluid by monolayer cultures].
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Ascitic Fluid↗
[Comparative bioavailability of fluorouracil and its prodrug, ftorafur, following intra-arterial, intravenous and preoral administration].
The blood-plasma levels in 28 patients, suffering from colorectal cancer with liver metastases, which were treated by a cyclic chemotherapy with fluorouracil (1) after p.o. and intraarterial (i.a.) administration of 1 or its prodrug ftorafur (2), respectively, were compared with those obtained after i.v. administration and the pharmacokinetics were calculated. In the case of 1 as well as of 2 the i.a. administration has been found to be optimal for distribution into the tumor tissue of liver metastases due to lowered blood-plasma concentrations. The absolute bioavailability, was 78% for p.o. and 57% for the i.a. administration of 1 respectively, and 98% for p.o. and 61% for the i.a. administration of 1 (given as 2), Accordingly, p.o. administration of both substances leads to therapeutical sufficiently high plasma levels with a steady state of css = 2.9 micrograms/ml/tss = 14 min for 1 and css = 3.5 micrograms/ml/tss = 20 min for 2.
Administration, Oral↗
[Pharmacokinetics and local availability of mitomycin. The influence of vasoconstriction and chemoembolization].
The influence of the vasopressin-pro-drug glycylpressine (GP) and of a chemoembolisation with Spherex starch-particles (SP) on the availability of mitomycin (CAS 50-07-7, mitomycin C, MMC) was investigated in 30 patients with liver metastases, MMC administration was performed after blocking of the common hepatic artery by different concentrations of SP and after different time-intervals of GP. The comparison of plasma-levels after bolus injection without GP and after administration of MMC after 2, 5 and 15 min of vasoconstriction and after chemoembolisation with 450 mg or 900 mg SP, respectively, showed a remarkable reduction in the systemic circulation of MMC in the blood vessel system at about 40% (GP) and 45% (SP). A statistically significant influence on the pharmacokinetics of MMC with regard to CO, Vd, T 1/2zp, AUC and Cl(tot) was found, but not in t1/2el, t1/2biol and Vl. Both methods cause a distinctly accelerated diffusion of MMC into the tissue of the tumor region by change of the hemodynamics, leading to lowered side-effects. Thus the clinical picture was improved by MMC.
Biological Availability↗