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Biomedical subjects

R A Bennett

Publications and source records attributed to R A Bennett.

66 records · Page 4Linked to original sources
PubMed1981

Effect of partial hepatectomy on removal of O6-methylguanine from alkylated DNA by rat liver extracts.

1. The activity of an enzyme catalysing the loss of O6-methylguanine from methylated DNA was increasing during liver regeneration after partial hepatectomy. Activity was increased 3-fold by 24h and was maximal (6-fold increase) over the period 48-72h after operation. 2. This activity could also be induced by chronic treatment with dimethylnitrosamine, but the maximal response amounted to a 2-3-fold change (with the greater effect in male rats) after 4-6 weeks of exposure to daily doses of 2 mg of dimethylnitrosamine/kg. 3. Neither partial hepatectomy nor treatment with dimethylnitrosamine increased the activities of two other enzymes repairing alkylated DNA, DNA (7-methylguanine-)glycosylase and DNA (3-methyladenine-)glycosylase. 4. These results therefore indicate that there is a selective induction of the O6-methylguanine removal system during hepatocyte proliferation. Since this product is known to lead to mutations and its persistence in DNA throughout cell replication has been implicated in tumour initiation, this induction may play a role in resistance to carcinogenesis by alkylating agents.

Alkylation↗
PubMed1981

Alkylation of DNA in rat tissues following administration of streptozotocin.

Streptozotocin, an antibiotic widely used for induction of diabetes in experimental animals and for the treatment of pancreatic neoplasms, was shown to be a potent methylating agent reacting with DNA in vitro to form methylated purines. The reaction was similar in extent and relative proportions of methylation products to that produced by N-methyl-N-nitrosourea, the aglycone of streptozotocin. When streptozotocin was administered to rats by i.v. injection, DNA was methylated with the formation of 7-methylguanine, O6-methylguanine, 3-methyladenine, and 7-methyladenine in liver, kidney, intestine, and pancreas. In contrast to N-methyl-N-nitrosourea which produced approximately equal amounts of methylation in DNA of liver, brain, and kidney, streptozotocin caused virtually no methylation in brain DNA; but, both liver and kidney DNA were alkylated to a greater extent than with N-methyl-N-nitrosourea. This methylation of renal DNA may account for the ability of streptozotocin to induce renal tumors. Streptozotocin produced significant methylation of pancreatic DNA which, if concentrated in the beta-cells, may account for their destruction. Pretreatment with nicotinamide reduced the extent of methylation of pancreatic DNA but did not affect the methylation in the liver or kidney. Methylation of beta-cell DNA in the pancreas may lead to the initiation of tumors if the extent of alkylation is not so great that cell death occurs.

Animals↗
PubMed1981

Excretion of an aflatoxin-guanine adduct in the urine of aflatoxin B1-treated rats.

Administration of aflatoxin B1 (AFB1) to rats resulted in the urinary excretion of 2,3-dihydro-2-(N7-guanyl)-3-hydroxyaflatoxin B1. This is the major product formed by the interaction in vivo of AFB1 with rat liver nucleic acids. The adduct was isolated from urine by the combined use of preparative and analytical high-pressure liquid chromatography and was quantitated by measurement of absorbance at 365 nm. The method allowed reproducible quantitation of adduct in urine samples from rats treated with AFB1 by i.p. injection at levels as low as 0.125 mg/kg. Application of the method to urine samples from rats given injections of AFB1 (1 mg/kg) revealed the presence of a compound chromatographically identical to authentic 2,3-dihydro-2-(N7-guanyl)-3-hydroxyaflatoxin B1. Spectral and chemical analysis of microgram quantities of this compound provided strong evidence that this compound is identical to authentic adduct. Measurement of this adduct in the urine of rats given injections of different doses of AFB1 showed that excretion occurs in a dose-dependent manner. Comparison of the dose-response curve for adduct excretion with that previously observed for adduct formation in rat liver DNA in vivo revealed a high degree of qualitative similarity, with the levels of adduct excreted in urine representing 30 to 40% of the levels seen initially in liver DNA.

Aflatoxin B1↗
PubMedDate not supplied

In vitro elution of gentamicin, amikacin, and ceftiofur from polymethylmethacrylate and hydroxyapatite cement.

OBJECTIVE: To compare the elution characteristics of ceftiofur and liquid and powdered gentamicin and amikacin from polymethylmethacrylate (PMMA) and from hydroxyapatite cement (HAC). METHODS: PMMA and HAC beads in triplicate were impregnated with various amounts and formulations of antibiotics. Beads were immersed in 5 mL of phosphate buffered saline that was replaced at 1, 3, 6, and 12 hours, and 1, 2, 3, 5, 7, 10, 14, 18, 22, 26, and 30 days. The eluent was stored at -70 degrees C until assayed within 2 weeks by microbiological assay (gentamicin and amikacin) or capillary electrophoresis (ceftiofur). RESULTS: Rate of elution for all beads was greatest within the first 24 hours. Cumulative release of total antibiotic dose from beads over 30 days was significantly greater from HAC than PMMA. Antibiotic elution was directly related to the amount of antibiotic incorporated into the cement. Powdered and liquid forms of gentamicin had similar elution rates from PMMA. Elution of amikacin from PMMA beads was greater when the powdered form was used compared with liquid amikacin. Eluent concentrations of ceftiofur were similar to those of the aminoglycosides during the first 3 to 7 days but then decreased precipitously by comparison. CONCLUSIONS: Elution of antibiotics from HAC was greater than from PMMA. Gentamicin- and amikacin-impregnated PMMA and HAC released bactericidal concentrations of antibiotic for at least 30 days. Ceftiofur-impregnated PMMA or HAC is unlikely to provide long-term bactericidal concentrations. CLINICAL RELEVANCE: Gentamicin and amikacin elute effectively from PMMA and HAC.

Amikacin↗
PubMedDate not supplied

Comparison of the strength and holding power of 4 pin designs for use with half pin (type I) external skeletal fixation.

The strength and holding power of four pin designs for use with half pin (type I) external skeletal fixation were evaluated. Pins that were tested were fully threaded, nonthreaded, two cortices partially threaded, and one cortex partially threaded. The study involved three parts: (1) resistance of the pins to axial extraction immediately after insertion; (2) resistance of the pins to axial extraction 8 weeks after being inserted into the tibiae of live dogs; and (3) resistance of the pins to bending load. Pins with threads engaging two cortices were more resistant to axial extraction than nonthreaded pins in both the acute (p less than 0.0001) and chronic (p less than 0.0001) studies. Nonthreaded pins were more resistant to bending than fully threaded and two cortices partially threaded pins (p less than 0.0005). One cortex partially threaded pins possessed similar bending strength to nonthreaded pins (p = 0.21) and had 5.3 times more resistance to axial extraction in the acute study (p less than 0.0001) and 6.9 times more in the chronic study (p less than 0.0001). Though one cortex partially threaded pins were not as resistant to axial extraction as pins with threads engaging two cortices (p less than 0.0001), they were more resistant to bending loads (p less than 0.0005). Loss of holding power and pin failure are two of the most serious problems associated with fracture stabilization using external skeletal fixation. The results of this study suggest that one cortex partially threaded pins are better at maintaining holding power and resisting bending and breaking than nonthreaded pins.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Vulvovaginectomy and perineal urethrostomy for neoplasms of the vulva and vagina.

Vulvovaginectomy and perineal urethrostomy were performed in three dogs with extensive neoplasms of the vulva and vagina. One benign tumor (fibroleiomyoma) and two malignant tumors (transitional cell carcinoma and anaplastic spindle cell sarcoma) were diagnosed. Survival times were 9 weeks to 10 months. Urinary continence was preserved in all three dogs. The procedure may be curative for benign tumors or malignant tumors that have not yet metastasized; it is a palliative procedure for advanced malignancies.

Animals↗