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Biomedical subjects

G Peter

Publications and source records attributed to G Peter.

At least 127 records · Page 7Linked to original sources
PubMed1978

[Sperm allergy of the anaphylactic type].

A case of an anaphylactic type of allergy is reported with pruritus, mucosal edema, asthma and shock symptoms which developed in a 26 year old female against her husbands sperma fluid. Symptoms and test results are compared with those of six other published cases. Results of skin tests obtained with a fraction of sperma plasma separated by chromatography are indicating that the antigen is of protein nature with a molecular weight of about 14.100. A molecular weight between 12.400 and 24.00 has also been reported in the literature.

Adult↗
PubMed1977

Mass spectrometric characterization of activated N-(2-chloroethyl)amino oxazaphosphorine derivative.

The hydroperoxy and several alkylthio derivatives of the antitumor agents cyclophosphamide (2-bis(2-chloroethyl)amino tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide), ifosfamide (3-(2-chloroethyl)-2-(2-chloroethylamino)tetrahydro-2H-1,3,1-oxazaphosphorine 2-oxide) and trofosfamide (3-(2-chloroethyl)-2-(bis(2-chloroethyl)amino)tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide) were characterized by electron impact and field desorption mass spectrometry. The compounds, which are stabilized derivatives of the activated hydroxylated intermediates of cyclophosphamide (ifosfamide, trofosfamide), could be identified as 4-hydroperoxy and 4-alkylthio oxazaphosphorines. The existence of diastereomers of these products was demonstrated by thin-layer chromatography and f.d. mass spectra. Derivatization with benzylmercaptan was found to be an appropriate method for the quantitative isolation and mass spectral identification of the activated metabolic intermediates of cyclophosphamide from biological material. Using this reaction, 4-hydroxycyclophosphamide and its acyclic tautomer, aldophosphamide, which are too unstable for direct identification, were detected in urine and serum of patients treated with 3H-cyclophosphamide.

Chemical Phenomena↗
PubMed1977

Characterization and quantitative estimation of activated cyclophosphamide in blood and urine.

An assay for the characterization and quantitative determination of activated cyclophosphamide has been described. The method is based on high reactivity of the kryptaldehyde group in 4-hydroxycyclophosphamide with mercapto compounds to yield 4-(S-R)mercaptocyclophosphamide derivatives. The activated cyclophosphamide can be converted quantitatively to 4-(S-benzyl)mercaptocyclophosphamide with benzyl mercaptan, and the mercapto derivative can be separated by thin-layer chromatography on silica gel with ethyl acetate:methyl ethyl ketone as solvent. Using this assay, significant levels of activated cyclophosphamide in the blood of mice and rats, as well as of humans, were found to be present after cyclophosphamide application. The characterization of 4-(S-benzyl)mercaptocyclophosphamide formed was confirmed by comparing the thin-layer chromatographic and mass spectrometric data on this derivative obtained from an authentic sample of 4-hydroxycyclophosphamide.

Animals↗
PubMed1976

[In vitro assay for cyclophosphamide-sensitivity of human tumours: the effect of 4-hydro-peroxy-cyclophosphamide on the incorporation of 3H-uridine into the nucleic acids of human tumour cells (author's transl)].

The utility of 4-hydro-peroxy-cyclophosphamide for testing the selectivity of human tumours cells against cyclophosphamide in vitro was studied. 4-hydro-peroxy-cyclophosphamide in aqueous solution spontaneously decomposes to 4-hydroxy-cyclophosphamide, the primary product of metabolic activation of cyclophosphamide thus representing a new form of "activated" cyclophosphamide. From 31 human tumours including 21 mammarian-, 4 ovarial-, 2 uterine-carcinomas, 2 seminomas, 1 hypernephroma and 1 rectum-carcinoma cell suspensions were made and the effect on the 3H-Uridine- and the 3H-Thymidine-incorporation into the nucleic acids after short time incubation with the effect of 4-hydro-peroxy-cyclophosphamide and 4-hydroxy-cyclophosphamide. 7 malignomas showed high sensitivity both against 4-hydro-peroxy-cyclophosphamide and against 4-hydroxy-cyclophosphamide. No additional inhibitory effect of the peroxyde function besides of that of the alkylating moiety of the molecule was found. Accordingly 4-hydro-peroxy-cyclophosphamide because of its better availibility and stability may be used as "activated" cyclophosphamide in screening tests for cyclophosphamide-sensivity of human tumours in vitro.

Adult↗
PubMed1976

Effect of clindamycin on aminoglycoside activity in a murine model of invasive Escherichia coli infection.

Previous studies have demonstrated that the early in vitro bactericidal activity of gentamicin and amikacin is inhibited by clindamycin. To investigate the possible clinical implications of these findings, the effect of clindamycin in combination with gentamicin or amikacin was compared with that of the aminoglycoside alone in the treatment of normal and neutropenic mice with Escherichia coli peritonitis and bacteremia. Mice treated with saline or clindamycin alone experienced rapid multiplication of bacteria in the peritoneal cavity, bacteremia, and subsequent death. Gentamicin or amikacin given 2 h after E. coli inoculation significantly reduced the mortality and peritoneal bacterial counts in normal and neutropenic mice in comparison with untreated controls. Prior or simultaneous administration of clindamycin with either aminoglycoside did not inhibit survival or bacterial clearance from the peritoneum. The only clindamycin effect was slight enhancement of survival of neutropenic mice treated with multiple doses of amikacin and clindamycin in comparison to those treated with amikacin alone.

Aminoglycosides↗
PubMed1976

Effect of clindamycin on the in vitro activity of amikacin and gentamicin against gram-negative bacilli.

The in vitro effect of clindamycin on the inhibitory and bactericidal activity of amikacin (BB-K8) and gentamicin against Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa was examined by the checkerboard technique in microtiter plates. Clindamycin (15 mug/ml) produced statistically significant increases in the minimal bactericidal concentrations of amikacin and gentamicin against E. coli and Klebsiellae at 2 and 4 h of incubation. The minimal bactericidal concentration against P. aeruginosa was not affected. Higher concentrations of clindamycin (20 to 25 mug/ml) reduced the minimal inhibitory and bactericidal concentrations of amikacin and gentamicin for E. coli at 18 h of incubation. The synergistic bactericidal activity of amikacin and carbenicillin against E. coli, but not P. aeruginosa, was also inhibited slightly by clindamycin (15 mug/ml). The clinical implications of this inhibition of the early bactericidal in vitro activity of aminoglycosides by clindamycin remain to be determined. Although these in vitro results have not been studied in clinical infections, it is conceivable that slight interference in early bacterial killing could alter the outcome of infection in the immunosuppressed patient.

Amikacin↗
PubMed1976

The problem of oncostatic specificity of cyclophosphamide (NSC-26271): Studies on reactions that control the alkylating and cytotoxic activity.

The relatively high oncostatic specificity of cyclophosphamide (CP) in vivo is shown to be due to the cytotoxic specificity of 4-hydroxycyclophosphamide (4-hydroxy-CP), the first product of metabolic activation of CP in the liver. This specificity can be evaluated not only in vivo by measuring the therapeutic index, but also in vitro by determining its cytotoxicity against Yoshida ascites tumor cells. Evidence is given that 4-hydroxy-CP is not an alkylating agent itself, but attains this property only by release of an alkylating N,N-(2-chloroethyl)phosphorodiamic acid moiety and acrolein. The energetic source for this rate-limiting toxication results from the resonance stabilization of the released acrolein. Reactions at the cryptoaldehyde group of 4-hydroxy-CP, which reduce or prevent the resonance stabilization of the 3-carbon unit to be released, lead to a deactivation of the primary metabolite of CP thus reducing or even preventing toxication, and hence influencing both the alkylating and cytotoxic activities of the molecule. Accordingly, it could be demonstrated by the reaction of 4-hydroxy-CP with thiols yielding 4-(S-R)-mercapto CP derivatives that the toxication of 4-hydroxy-CP can be controlled under physiologic conditions of pH and temperature. In the case of free protein sulfhydryl groups, this reaction also leads to fixation onto a macromolecule of the CP metabolite. On the basis of these peculiar reactivities of the oxazaphosphorine ring of 4-hydroxy-CP and of the partial reaction kinetics involved during toxication or deactivation, the significance of these findings to the problem of CP specificity is discussed.

Alkylating Agents↗
PubMed1976

Deactivation of cyclophosphamide (NSC-26271) metabolites by sulfhydryl compounds.

The reaction of 4-hydroxycyclophosphamide (4-hydroxy-CP) with sulfhydryl (SH) compounds was studied, and although the cytotoxic activity was lost a significant stabilization of the alkylating capacity was observed at the same time. We were able to show that the reaction of 4-hydroxy-CP with thiols lead to an equilibrium between the reaction product and the starting substrates. On the basis of this equilibrium the increased stabilization of the alkylating capacity of the 4-hydroxy-CP derivatives by raising the SH concentration can be explained. The different degrees of stabilization depending on the structure of the thiol results from different equilibria. the effect on the toxification reaction resulting from this equilibrium, in connection with the tautomeric equilibrium between 4-hydroxy-CP and aldophosphamide, is discussed.

Acetylcysteine↗
PubMed1976

Studies on 4-hydroperoxycyclophosphamide (NSC-181815): a simple preparation method and its application for the synthesis of a new class of "activated" sulfur-containing cyclophosphamide (NSC-26271) derivatives.

4-Hydroperoxycyclophosphamide was obtained in approximately 20% yield by ozonization of cyclophosphamide in acetone/water at 0 degrees C. It was reduced to 4-hydroxycyclophosphamide, which was treated with several mercaptans to yield compounds of the type 4-(S-R)-mercapto-cyclophosphamide. In the solid state these compounds are stable at room temperature; in aqueous solution they are hydrolyzed to 4-hydroxycyclophosphamide or its tautomer, aldophosphamide. One of the 4-(S-R)-mercapto-cyclophosphamide compounds was tested biologically in vitro against Yoshida ascites tumor cells and showed the same cytotoxic activity as 4-hydroxycyclophosphamide.

Alkylating Agents↗
PubMed1976

Characterization of cyclophosphamide (NSC-26271) metabolites and related derivatives by field-desorption and electron-impact mass spectrometry.

Several important metabolites of cyclophosphamide (CP), such as 4-hydroxycyclophosphamide and phosphoramide mustard, some 4-alkyl(aryl)thio derivatives have been investigated by field-desorption and electron-impact mass spectrometry. The structural identification of synthetic compounds and of derivatives, isolated by thin-layer chromatography in vitro, was possible since complementary information can be obtained using the two ionization techniques. Whereas only the field-desorption mass spectra showed more abundant molecular ions, the electron-impact technique revealed a characteristic fragmentation pattern for most of the compounds studied. Examples are given which demonstrate the existence of stereoisomers of CP derivatives using thin-layer chromatography and field-desorption mass spectrometry. The results indicate that field-desorption mass spectrometry is also a particularly appropriate method for the characterization of unstable CP metabolites in vivo.

Chemical Phenomena↗
PubMed1976

Synthesis of 4-hydroperoxy derivatives of ifosfamide and trofosfamide by direct ozonation and preliminary antitumor evaluation in vivo.

A one-step synthesis of 4-hydroperoxyifosfamide and 4-hydroperoxytrofosfamide is described. The method involves direct ozonation of ifosfamide and trofosfamide and offers improved yields in comparison with Fenton oxidation and greater convenience in comparison with ozonation of the appropriate 3-butenyl phosphorodiamidate. Evaluation of the 4-hydroperoxy derivatives of cyclophosphamide, ifosfamide, and trofosfamide against leukemia L1210 in vivo suggests a superior effect for the ifosfamide derivatie.

Animals↗