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Biomedical subjects

B Gold

Publications and source records attributed to B Gold.

At least 91 records · Page 5Linked to original sources
PubMed1987

Isotonic (dynamic) and isometric (static) effort in the assessment and evaluation of diastolic hypertension: correlation and clinical use.

We compared the effect of two exercise stress tests on blood pressure in normal and borderline populations. The aim of the trial was to determine if isometric exercise testing by handgrip can replace the isotonic exercise test in population screening for the detection of mild and latent hypertension. The study involved 150 subjects; 62 were normotensive and 88 were borderline hypertensive. No significant statistical difference was found in diastolic pressure between the tests. In normotensive subjects, the diastolic response after isotonic effort was 79.3 +/- 9.6 mm Hg and 89.0 +/- 9.7 mm Hg after the isometric test (p less than 0.05). However, both results did not pass 100 mm Hg. In borderline hypertensive patients the diastolic response to the isotonic test was 105.6 +/- 8.8 mm Hg and after the isometric test 107.7 +/- 10.6 mm Hg (NS). The results show that the handgrip isometric test can replace the complicated isotonic test for the screening detection and evaluation of hypertensives in the population.

Adult↗
PubMed1987

Mechanism of inhibition of N-methyl-N-nitrosourea-induced mutagenicity and DNA binding by ellagic acid.

Ellagic acid (EA) is a dilactone derivative of shikimic acid, which is found in a variety of soft fruits and vegetables. EA inhibits mutagenesis and carcinogenesis induced by benzo[a]pyrene and its bay-region dihydrodiol epoxide derivative by preventing their covalent binding to DNA. EA at concentrations of 100, 250, 500 and 1000 nmol/plate inhibited the mutagenicity of N-methyl-N-nitrosourea (MNU) (400 nmol/plate) in Salmonella typhimurium TA100 by 3, 13, 45 and 60%, respectively. A study of inhibition of 3H-MNU-mediated DNA methylation by EA showed that it inhibited only the formation of O6-methylguanine, while attack at the N7 and N3 positions of guanine and adenine, respectively, was not altered. This inhibition was observed only in double-stranded DNA. Ultraviolet and equilibrium dialysis studies show that EA has a definite affinity for DNA, but that an intercalating process is not involved.

Animals↗
PubMed1986

Inhibition of N-methyl-N-nitrosourea-induced mutagenicity and DNA methylation by ellagic acid.

Ellagic acid, a naturally occurring plant phenol, inhibits the activity of the direct-acting mutagen N-methyl-N-nitrosourea (MeNU) in Salmonella typhimurium TA100. Ellagic acid at 0.10, 0.25, 0.50, and 1.00 mM inhibited the mutagenicity of MeNU (0.40 mM) by 3%, 13%, 45%, and 60%, respectively. Ellagic acid (3 mM) also inhibited the mutagenic activity of N,N-dimethylnitrosamine (25-200 mM) in the presence of pyrazole-induced rat liver fraction S-9. The effect of ellagic acid on DNA methylation was studied by incubating 0, 0.72, 1.32, 2.64, and 6.60 mM ellagic acid with DNA (0.9 mM nucleotide) and [3H]MeNU (0.66 mM). HPLC analysis of DNA hydrolysates showed that ellagic acid caused a dose-dependent 36-84% decrease in O6-methylguanine but only a 20% decrease in the 7-methylguanine adduct. Under conditions where methylation at the O6 position of guanine in double-stranded DNA was inhibited 65% by ellagic acid, no significant inhibition of either O6- or 7-methylguanine formation was detected in single-stranded DNA. Affinity-binding studies revealed that [3H]ellagic acid binds equally to double-stranded or single-stranded DNA but that poly(dA X dT) binds 1.5 times as much ellagic acid as does poly(dG X dC). The binding of ellagic acid to DNA is dependent on the concentration of both ellagic acid and DNA. The specific inhibition of O6-methylguanine formation only in double-stranded DNA and the relatively low inhibition of 7-methylguanine formation rule out the possibility that ellagic acid prevents DNA alkylation by scavenging the electrophilic intermediate generated in the hydrolysis of MeNU. The results suggest that ellagic acid inhibition of MeNU-induced mutagenicity is due to specific inhibition of methylation at the O6 position of guanine through an ellagic acid-duplex DNA affinity-binding mechanism.

Benzopyrans↗
PubMed1986

The effect of subchronic feeding of 1,1-dichloro-2,2-bis(4'-chlorophenyl)ethene (DDE) on its metabolism in mice.

1,1-Dichloro-2,2-bis(4'-chlorophenyl)ethene (DDE), a major lipophilic metabolite of 1,1,1-trichloro-2,2-bis(4'-chlorophenyl)ethane (DDT), is a hepatic carcinogen in both the mouse and hamster upon chronic exposure. DDT is tumorigenic only in the former species. The metabolism in the mouse of [14C-UL-phenyl]DDE with and without 5-month DDE pretreatment, is reported. The urine, feces and liver were analyzed and in all cases most of the radioactivity observed was identified as unchanged DDE. The only metabolite identified was the phenolic derivative 1,1-dichloro-2-(4'-chlorophenyl)-2-(3"-hydroxy-4"-chlorophenyl)ethene, which was found in significant amounts only in the feces. No other potential metabolites derived from the oxidation of DDE were observed. The effect that pretreatment with DDE had on its own metabolism was to decrease the urinary excretion of DDE and to increase the hepatic levels. It appears from these results that any oxidative metabolism of DDE constitutes a very insignificant pathway in the mouse. It is also concluded that there is no significant change in the metabolism of DDE after prolonged exposure to the pesticide, and there is no indication for the metabolism of DDE to a reactive electrophilic species.

Animals↗
PubMed1985

Ceftazidime in the treatment of meningitis in infants and children over one month of age.

Ceftazidime, a new beta-lactamase-resistant cephalosporin, was compared with a combination of ampicillin and chloramphenicol for the treatment of meningitis in 100 infants and children aged one month to 15 years. In this open, randomized trial conducted in the Dominican Republic, 61 patients received 50 mg/kg of ceftazidime intravenously every eight hours; 39 received ampicillin plus chloramphenicol in conventional dosages. Seventy-eight of the patients had discernible isolates in samples from cerebrospinal fluid, six had a positive diagnostic Directogen result, and the remainder either had miscellaneous pathogens evident in samples of cerebrospinal fluid, bacteriologic growth in cultures of blood samples only, or no bacteriologic growth in cultures of either cerebrospinal fluid or blood. Among patients with discernible etiologic agents in samples of cerebrospinal fluid, 11 of 57 (19 percent) ceftazidime-treated patients died, and five of 27 (19 percent) patients treated with the combination died. Mortality by pathogen was as follows for patients who received ceftazidime or ampicillin plus chloramphenicol, respectively: Hemophilus influenzae, two of 27 (7 percent) and one of 15 (6 percent); Streptococcus pneumoniae, six of 12 (50 percent) and two of five (40 percent); Neisseria meningitidis, none of 11 (0 percent) and one of six (17 percent); and Salmonella, neither of two (0 percent) and one of one (100 percent). Overall mortality in the ceftazidime group was 20 percent versus 21 percent in the combination group. No significant toxicities were noted in the patients treated with ceftazidime.

Adolescent↗
PubMed1985

Axonal transport of neurofilament proteins in IDPN neurotoxicity.

The neurofibrillary changes produced by IDPN are the consequence of the ability of the agent to impair the slow axonal transport of neurofilaments. The susceptibility of various neurons to this effect depends upon their neurofilament content; neurofilament-rich large caliber axons are severely affected. In motor neurons the half-velocities of neurofilament proteins are reduced 2-10 fold, while tubulin and other slow component constituents are only mildly altered. Optic nerve fibers are intermediate in vulnerability, and small neurofilament-poor fibers have little change in slow transport. The agent acts directly on the axon, and the transport defect is expressed all along the course of susceptible axons. Similar alterations in neurofilament transport have recently been found with 3,4-dimethyl-2,5-hexanedione, indicating that similar pathogenetic mechanisms can occur with toxic agents other than IDPN.

Animals↗
PubMed1985

In vitro and in vivo formation of 7-(2'-carboxyethyl)guanine from the liver carcinogen 1-nitroso-5,6-dihydrouracil and its reactions with water and methanol.

Base-catalyzed hydrolysis of the potent liver carcinogen 1-nitroso-5,6-dihydrouracil [(NDHU) CAS: 16813-36-8] afforded 3-hydroxypropionic acid and acrylic acid in 72 and 6% yield, respectively. The base-catalyzed methanolysis of NDHU gave quantitative yields of 3-methoxypropionic acid and methyl carbamate. These results indicate that base-catalyzed NDHU decomposition produces a 2-carboxyethyl carbonium-ion-type intermediate. When 3H-labeled NDHU was reacted at pH 8 with DNA and RNA, 7-(2'-carboxyethyl)guanine (CEG) was detected in the hydrolysate and was identified by its cochromatography with authentic CEG in five (for DNA) or three (for RNA) systems and by a reverse isotope-dilution procedure. Radioactively labeled CEG (identified as before) and five other labeled chromatographic fractions were present in liver DNA and RNA hydrolysates after [3H]NDHU was gavaged into MRC Wistar rats. These fractions persisted in the liver DNA for various times up to 33 days after the gavage. The CEG fraction was 94% of the radioactivity in DNA reacted in vitro, but it reached only 21% of the radioactivity in the liver DNA. The results are related to a study on single-strand breaks produced by NDHU in rat liver DNA.

Animals↗
PubMed1984

A mechanistic study of the metabolism of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane (DDD) to 2,2-bis(p-chlorophenyl)acetic acid (DDA).

The metabolism of [1-2H]-1,1-dichloro-2,2-bis(p-chlorophenyl)ethane (DDD-d) and [1-2H]-1-chloro-2,2-bis(p-chlorophenyl)ethene (DDMU-d) and their corresponding non-deuterated isomers DDD and DDMU was studied in female Swiss mice over a 96-hr period. The only detected urinary metabolite of DDD-d and DDD was 2,2-bis(p-chlorophenyl)acetic acid (DDA). Animals administered DDD excreted approximately 2.4-fold more DDA than those treated with DDD-d over the total collection period. The initial (0-36 hr) linear excretion rates of DDA for DDD and DDD-d were 17.1 and 5.5 micrograms/hr respectively. DDMU- and DDMU-d-treated mice excreted significant quantities of DDA, 2,2-bis(p-chlorophenyl)ethanol (DDOH) and 2,2-bis(p-chlorophenyl)ethanol (DDCHO). The only quantitative difference between DDMU and DDMU-d was that the non-deuterated isomer afforded approximately 1.8 times more DDA over the 96-hr collection. The initial (0-36 hr) linear excretion rates of DDMU and DDMU-d were 10.7 and 6.2 micrograms/hr respectively. The qualitative and quantitative results are consistent with DDD being metabolized to DDA via enzyme-mediated hydroxylation on the C-1 side chain carbon.

Animals↗
PubMed1984

Evidence for penetration of the nuclear envelope by N-nitrosomethylhydroxymethylamine.

The metabolic activation of N-nitrosamines to alkylating agents is mediated by the hydroxylation of the carbon adjacent to the N-nitroso moiety. The resulting N-nitroso-alpha-hydroxy-amines are unstable and decompose to an aldehyde or ketone and a syn-alkane diazotic acid, the latter species being responsible for the carbenium ion reactions associated with nitrosamine-induced alkylation of DNA. Since this chain of events is thought to be initiated in the cytoplasm, there must be a 'transportable' metabolite that can diffuse through the cytoplasm, penetrate the nuclear envelope and alkylate the DNA therein. The 'transportability' of N-nitrosomethylhydroxymethylamine, the putative proximate metabolite of N-nitrosodimethylamine, has been assessed by incubating N-nitroso- ([14C]-methyl)-methylacetoxymethylamine with intact rat liver nuclei in the presence and absence of esterase. The results obtained demonstrate the ability of the in-situ-generated N-nitroso-alpha-hydroxyamine to penetrate the nuclear envelope and confirm that these unstable metabolites are 'transportable' proximate carcinogens.

Animals↗
PubMed1983

alpha-chloroepoxides. 2. Mutagenicity of 1-chlorocyclohexene oxide and its thermal isomerization product, 2-chlorocyclohexanone.

The pseudo-first-order hydrolysis rate constants in pH 7.4 buffer-acetone solution are reported for 1-chlorocyclohexene oxide and 2-chlorocyclohexanone at 0, 25 and 37 degrees C. The rate constants, in conjunction with product studies, demonstrate that the hydrolysis of 1-chlorocyclohexane oxide quantitatively affords 2-hydroxycyclohexanone and that there is no significant isomerization of 1-chlorocyclohexene oxide to 2-chlorocyclohexanone during the hydrolysis. Both 1-chlorocyclohexene oxide and 2-chlorocyclohexanone were reacted with 2-aminopyridine, a model for adenine, to yield the same product, N-(2'-pyridyl)-2-aminocyclohexanone. The mutagenicity of 1-chlorocyclohexene oxide and 2-chlorocyclohexanone in the Ames liquid incubation assay using TA100 shows 2-chlorocyclohexanone to be slightly more active than 1-chlorocyclohexene oxide, in spite of the finding that 1-chlorocyclohexene oxide is clearly a more reactive electrophile than 2-chlorocyclohexanone. These results are interpreted to indicate the important role that hydrolysis (detoxification) plays in the in vitro evaluation of the proposed ultimate electrophilic metabolites of chloroolefins.

Chemical Phenomena↗