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Biomedical subjects

B Gold

Publications and source records attributed to B Gold.

At least 19 recordsLinked to original sources
PubMed1992

The effect of ellagic acid on xenobiotic metabolism by cytochrome P-450IIE1 and nitrosodimethylamine mutagenicity.

Ellagic acid (EA) is an inhibitor of the in vitro mutagenicity of N-nitrosodimethylamine (NDMA) in Salmonella typhimurium strain TA100 using pyrazole-induced rat liver 9000 x g supernatant (S-9). In order to understand this activity, the effect of EA on the metabolic hydroxylation of 4-nitrophenol, a substrate, as is NDMA, for cytochrome P-450IIE1 was studied using pyrazole induced rat S-9 and microsomal protein. It is shown that EA has an inhibitory effect on 4-nitrophenol hydroxylase with both enzyme preparations. This effect on cytochrome P-450IIE1 may be responsible, at least in part, for the inhibition of NDMA mutagenicity by EA.

Animals↗
PubMed1991

[Evaluation of verapamil for hypertension by an isometric exercise test].

Since the resting blood pressure (BP) does not predict round-the-clock values, in order to evaluate the disease and its response to treatment BP should be measured during exertion. Verapamil, either 120 mg or 160 mg, twice daily, was given to 60 hypertensives at rest and during isometric effort, according to our previously reported protocol. There was a significant response (p less than 0.005) to the treatments. Sustained release verapamil, 240 mg once a day, reduced systolic and diastolic BP significantly in 38 of 45 hypertensives at rest and during isometric effort. A simple, inexpensive, cost-effective, hand-grip method is strongly recommended as an integral part of treatment evaluation. The combination of highly effective drugs together with a simple method of BP evaluation may result in improved long-term treatment.

Blood Pressure↗
PubMed1991

Control over the sequence specificity of DNA alkylation: syntheses and reactions with 32P-end-labelled DNA of N-alkyl-N-nitrosoureas linked to minor groove binding lexitropsins.

The syntheses of N-2-chloroethyl-N-nitrosoureas (Cl-ENU) that are covalently linked to a series of minor groove binding lexitropsins related to distamycin A are reported. The lexitropsins of 2-Cl-ENU show a sequence specificity for alkylating an adenine toward the ends of its DNA affinity binding domains. The reaction of DNA with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea does not yield these products. Therefore, the linking of the 2-Cl-ENU to the minor groove binder qualitatively and quantitatively alters the DNA observed.

Alkylation↗
PubMed1991

Influence of calcium channel blockers on polymorphonuclear and monocyte bactericidal and fungicidal activity.

The effect of calcium channel blocking agents on the killing activity of human peritoneal polymorphonuclears (PMN) and monocytes was studied. The organisms used were Escherichia coli, Staphylococcus aureus and Candida albicans. The pharmacological concentration of verapamil (5 microM), nifedipine (10 microM) and diltiazem (10 microM) caused a similar inhibition of killing activity in both PMN and monocytes. The calcium channel blockers significantly reduced the in vitro killing of E. coli, S. aureus and C. albicans by PMN to about 47%, 30% and 20% respectively, compared with 81 +/- 6%, 65 +/- 5% and 40 +/- 4% in the controls. The killing of these organisms by monocytes was 60 +/- 6%, 42 +/- 7% and 35 +/- 5% respectively, as compared with 30%, 20% and 17% in the presence of these drugs. The bactericidal activity of the phagocytic cells from patients under treatment with calcium channel blockers was not affected and was found to be within the normal range, indicating that calcium channel blockers do not cause an irreversible impairment in PMN and monocyte killing activity. However, their potential inhibition of phagocytic cell activity should be taken into consideration during treatment.

Adult↗
PubMed1990

N-(2-chloroethyl)-N-nitrosoureas covalently bound to nonionic and monocationic lexitropsin dipeptides. Synthesis, DNA affinity binding characteristics, and reactions with 32P-end-labeled DNA.

The synthesis and characterization of a series of compounds that contain an N-alkyl-N-nitrosourea functionality linked to DNA minor groove binding bi- and tripeptides (lexitropsins or information-reading peptides) based on methylpyrrole-2-carboxamide subunits are described. The lexitropsins (lex) synthesized have either a 3-(dimethylamino)propyl or propyl substituent on the carboxyl terminus. The preferred DNA affinity binding sequences of these compounds were footprinted in 32P-end-labeled restriction fragments with methidiumpropyl-EDTA.Fe(II), and in common with other structural analogues, e.g., distamycin and netropsin, these nitrosoureas recognize A-T-rich runs. The affinity binding of the compound with the dimethylamino terminus, which is ionized at near-neutral pH, appeared stronger than that observed for the neutral dipeptide. The sequence specificity for DNA alkylation by (2-chloroethyl)nitrosourea-lex dipeptides (Cl-ENU-lex), with neutral and charged carboxyl termini, using 32P-end-labeled restriction fragments, was determined by the conversion of the adducted sites into single-strand breaks by sequential heating at neutral pH and exposure to base. The DNA cleavage sites were visualized by polyacrylamide gel electrophoresis and autoradiography. The alkylation of DNA by Cl-ENU-lex was compared to that by N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosourea (CCNU), which has no DNA affinity binding properties. While all the Cl-ENU compounds generate DNA breaks as a consequence of the formation of N7-alkyl-guanine, the Cl-ENU-lex compounds induced, in a time- and dose-dependent fashion, intense DNA cleavage bands at adenine, cytosine, and thymine residues associated with affinity binding sites. These non-G cleavages induced by Cl-ENU-lex were inhibited by the coaddition of distamycin at concentrations that did not affect G alkylation break sites. CCNU, even at much higher concentrations, does not generate any similar detectable lesions at non-G sites. Therefore, linking the Cl-ENU moiety to minor groove binders is a viable strategy to qualitatively and quantitatively control the delivery and release of the ultimate DNA alkylating agent in a sequence-dependent fashion.

Alkylation↗
PubMed1989

Reflex sympathetic dystrophy syndrome following minor trauma.

The reflex sympathetic dystrophy syndrome (RSDS) is an excessive or exaggerated response of an extremity to injury, manifested by burning pain, vasomotor disturbances, delayed functional recovery and trophic changes. The most common precipitating event is trauma. Early initiation of treatment improves therapeutic success. We describe three patients with RSDS, and discuss the prevalence, diagnosis and treatment of this condition. Physicians in primary care, traumatology and occupational medicine clinics should be aware of the clinical characteristics of this infrequent complication of limb trauma in order to avoid unnecessary diagnostic procedures and delay in treatment.

Adult↗
PubMed1988

Synthesis of an N-methyl-N-nitrosourea linked to a methidium chloride analogue and its reactions with 32P-end-labeled DNA.

The synthesis and characterization of an N-methyl-N-nitrosourea (MNU) analogue that is covalently linked to a methidium nucleus is described. At 37 degrees C in pH 8.0 buffer 9 hydrolyzes via pseudo-first-order kinetics, with a calculated t1/2 = 77 min. By use of polyacrylamide sequencing gels the formation of piperidine-labile N7-methylguanine adducts from the reaction of 9 and MNU with 5'-32P-end-labeled DNA restriction fragments is reported. DNA methylation by 9 in 10 mM Tris buffer is enhanced with increasing ionic strength (50-200 mM NaCl), which contrasts to the inhibition of MNU-induced cleavage with increasing salt. In addition, 9 methylates all G sites equally, while MNU shows a clear preference for d(G)n (n greater than or equal to 3) runs and an asymmetrical methylation pattern within these G-rich regions. The results are discussed in terms of the delivery of the MNU moiety to the DNA target by a non-sequence-specific intercalation process and the subsequent hydrolytic generation of a nondiffusible alkylating intermediate.

Base Sequence↗
PubMed1988

The effect of pyrazole, phenobarbital, ethanol and 3-methylcholanthrene pretreatment on the in vivo and in vitro genotoxicity of N-nitrosopyrrolidine.

The in vitro genotoxicity of N-nitrosopyrrolidine (NPy) has been studied in Salmonella typhimurium strain TA1535 in the presence of untreated and pyrazole-, phenobarbital (PB)-, 4-day ethanol (EtOH)-, 10-day EtOH- and 3-methylcholanthrene (3-MC)-pretreated male Sprague-Dawley rat liver S-9 fractions. Unless stated otherwise, the last pretreatment exposure was 24 h prior to sacrifice and isolation of hepatic enzymes. Pyrazole and EtOH (10-day exposure) both effectively induced the conversion of NPy into a mutagen at doses as low as 500 microM. PB and EtOH (4-day exposure) had a modest enhancing effect on the number of revertants scored, while 3-MC and uninduced S-9 fractions gave results not significantly different from background (no NPy). The same pretreatment protocols were used to determine the in vivo genotoxicity of NPy in rat liver using the technique of alkaline elution. The inducing agents had the exact opposite effect in vivo with control, 3-MC- and 4-day EtOH-treated animals showing the highest level of DNA damage. Pyrazole and 10-day EtOH pretreatments gave DNA elution rate constants comparable to animals not treated with NPy. However, in 10-day EtOH-pretreated animals which were administered NPy without a 24-h interval between EtOH and NPy exposure, DNA damage was observed at the same high levels as was seen in uninduced and 3-MC treated rats. The results are discussed in terms of a detoxification role for microsomal proteins and that the observed in vivo DNA damage may be induced by enzymes associated with the nuclear compartment.

Animals↗