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Biomedical subjects

R Albanese

Publications and source records attributed to R Albanese.

At least 19 recordsLinked to original sources

Metaphit amplifies long-term potentiation (LTP) in the mouse hippocampus.

The influence of metaphit, a phencyclidine derivative, on the amplitude of Long-Term Potentiation (LTP) in the mouse hippocampus was investigated. Mice (C57BL/6) of both sexes were injected with metaphit (80 mg/kg) and hippocampal slices were prepared at 3, 24, 48 hrs and 6 days following injection. The extracellular evoked potentials were recorded from the pyramidal cell layer following Schaffer collateral stimulation. The threshold value, defined as the minimum strength of the stimuli to evoke a 0.1 mV potential, was about 5 fold greater in metaphit slices than in control slices 3 hr following injection, and then declined to the control value within 6 days. The magnitude of LTP was also amplified by metaphit in a time-dependent fashion. The effect was visible three hours after injection, reached its maximum at 48 hr and then declined to a level slightly higher than control at 6 days following injection. These results demonstrate that metaphit, a compound known to induce audiogenic seizures, is able to modify synaptic plasticity in the hippocampus. Presented results are also in agreement with our previous data which demonstrated an interaction between the mechanisms of LTP and audiogenic seizure.

Animals

Ultrashort electromagnetic signals: biophysical questions, safety issues, and medical opportunities.

Ultrashort electromagnetic pulses are being increasingly produced by modern high power microwave and laser devices. These ultrashort pulses can produce electromagnetic transients in tissue that prompt safety questions concerning the possible exposure of living beings to ultrashort electromagnetic pulses. The existence of electromagnetic transients may permit meaningful advances in medical therapy and imaging. Electromagnetic transients, potential medical applications, and anticipated research avenues relevant to occupational health and safety issues are discussed.

Biophysical Phenomena

Transurethral microwave thermotherapy in the treatment of symptomatic benign prostatic hyperplasia.

One hundred and forty-four patients with symptomatic benign prostatic hyperplasia were treated by transurethral microwave thermotherapy between January and December 1991. Before entering the study, all patients had a Boyarsky symptom score > or = 8, peak flow rate < or = 15 ml/s and postvoiding residual urine < or = 200 ml. Transurethral thermotherapy with the Prostatron (Technomed) was carried out as a single session (60 min) without any analgesia or sedation. Acute urinary retention occurred in 19.4% of the patients after treatment requiring catheterization for 2-3 weeks; morbidity rate was 5.5%. Six months after treatment, Boyarsky symptom score decreased from 11.73 +/- 4.97 to 4.40 +/- 3.21 (mean values +/- SD); peak flow rate increased on average from 8.97 +/- 4.18 to 13.07 +/- 4.87 ml/s and postvoiding residual urine decreased from 135 +/- 17.9 to 63 +/- 34.7 ml. Slight further improvement was shown, in a few patients, at the 1-year follow-up visit.

Catheterization

[Surgical treatment of unrepairable vesicovaginal fistulas].

The authors discuss different types of urinary diversion as the therapy of unrepairable vesico-vaginal fistulas. They also describe the therapy performed in their experience and underline that, at the moment, rectal bladder is to be considered the best solution.

Colon

Mutagenicity to bacteria, cultured cells, and rodents of the human carcinogen chlornaphazine.

The human carcinogen and nitrogen mustard chlornaphazine (CN) has been confirmed to be mutagenic to Salmonella and, unexpectedly, the more so when evaluated in the presence of liver S9 mix. It also has been established as clastogenic to Chinese hamster lung cells exposed in vitro to dose levels greater than 2.5 micrograms/ml. Chlornaphazine subdued mice at doses of 5 g/kg, but only the occasional death occurred during the 4 days following oral administration of this dose in corn oil. Consequently, a median lethal dose level was not established. Nonetheless, dose levels of 500 mg/kg or greater gave a clear positive response in both the mouse and the rat bone marrow micronucleus assay. Although depression of erythropoeisis was observed in mice, a clastogenic response still was observed in the bone marrow 24 hr after dosing. The positive response in the rat was greater than that observed in the mouse. The present data provide a further instance of an established human carcinogen being readily detected by standard in vitro and in vivo mutagenicity assays.

Animals

Species-specific response to the rodent carcinogens 1,2-dimethylhydrazine and 1,2-dibromo-3-chloropropane in rodent bone-marrow micronucleus assays.

1,2-Dimethylhydrazine is confirmed as active in the mouse bone-marrow micronucleus assay when administered as an aqueous solution via oral gavage to three different strains of mice. It is also shown to be inactive in a corresponding rat assay under similar conditions of test. The observations were independently repeated in two laboratories. In contrast, 1,2-dibromo-3-chloropropane showed the reverse profile, being active in the rat bone-marrow assay but inactive in the mouse; the latter observations were also made in two laboratories. The carcinogen procarbazine was active in both species. These findings are discussed within the context of the present GeneTox revision of the standard test protocol of the rodent bone-marrow micronucleus assay.

1,2-Dimethylhydrazine

Chemically induced aneuploidy in female germ cells.

Female mice were dosed with the spindle poisons colcemid (5 mg/kg) or colchicine (2 mg/kg) or with a dihydropyridazinone (ICI 109,081; 5 mg/kg; which inhibits oocyte maturation) or with saline, the vehicle control. The dosed females (whose ovulation was synchronized using exogenous gonadotrophins) were mated with undosed males, 12 or 3 h prior to ovulation, coresponding to MI or MII stages in preovulatory oocytes. First-cleavage embryos derived from these matings were then analysed for numerical chromosome aberrations. There were no numerical aberrations in the embryos derived from control matings. Polyploid embryos were isolated from females dosed with colchicine. When females were dosed 3 h prior to ovulation (PO) 26% of the first-cleavage embryos were polyploid; in those dosed 12 h PO it was 100%. Colcemid and ICI 109,081 induced both polyploid and aneuploid embryos; with colcemid these aberrations were only observed in the embryos derived from oocytes of females dosed 3 h PO. At this sample time 4% of the embryos were polyploid and 24% were aneuploid. In contrast, the majority of aberrations induced by ICI 109,081 were observed in females dosed 12 h PO where 10% of the embryos were polyploid and 3% were aneuploid.

Aneuploidy

Induction and transmission of chemically induced chromosome aberrations in female germ cells.

Female mice were dosed with a number of chemical clastogens. The dosed females were then mated 28.5, 6.5, and 0.5 days after dosing, corresponding to various developmental stages of oogenesis (ie, early pre-antral to late antral stages). One-cell embryos derived from these mating were then isolated and analysed for structural and/or numerical chromosome aberrations. Chromosome damage, either structural or numerical, was induced only in oocytes at the late antral stages of oogenesis (i.e. when females were dosed 0.5 days prior to mating). There were few chromosome aberrations in embryos obtained from females dosed 6.5 or 28.5 days prior to mating. The results show that the analysis of one-cell embryos derived from the germ cells of dosed females is a potentially useful test system for the identification of chemically induced structural and numerical chromosome aberrations. However, the technically demanding methods involved in the preparation of these one-cell embryos prevent their use for routine screening purposes.

Abnormalities, Drug-Induced

The cytonucleus test in the rat: a combined metaphase and micronucleus assay.

The suitability of the rat as a species choice for the micronucleus assay and the possibility of combining both metaphase and micronucleus analysis using one set of animals were investigated. Cyclophosphamide, trenimon, vinblastine sulphate and dimethyl benzanthracene were used to optimise the study design and experimental procedures. The sample times ranged from 12 to 72 h after a single dose of the compound. A maximal response in both micronucleus and chromosome aberration induction was observed 24 h after dosing. This sample time is recommended as the single sample time for the screening of all classes of compound. Using the optimal conditions, a number of different mutagens/carcinogens were then analysed for the induction of both micronuclei and chromosome aberrations in the same animal. The compounds selected were mitomycin C, methotrexate, 5-fluorouracil, hexamethyl phosphoramide, benzo[a]pyrene, benzidine and diaminoterphenyl. The results show that the rat is a responsive test species and that it is possible to combine both metaphase and micronucleus analysis in the same animal.

Animals

The assessment of micronucleated polychromatic erythrocytes in rat bone marrow. Technical and statistical considerations.

Traditionally, the mouse is the species of choice for the rodent bone marrow micronucleus assay (MN). However, the rat is used for most other toxicological studies. The suitability of the rat as a test species for the MN was therefore investigated. In this paper, the methodological aspects of the assay have been considered. The distribution and incidence of micronucleated polychromatic erythrocytes (MPEs) on bone marrow slides prepared by two techniques, the conventional smear and the paint-brush technique, were assessed in control and cyclophosphamide-dosed male and females rats. MPEs were shown to be homogeneously distributed when assessed over a large number of PEs on slides prepared by both techniques, but when viewed over a few hundred PEs (less than 500 PEs), the incidence of MPEs on the same slides was seen to vary considerably (0-10 MPEs/500 PEs). Variability was within acceptable limits when at least 1000 PEs/animal were analysed. The spontaneous incidence of MPEs in the AP rat is low (0-2 MPEs/1000 PEs). Cyclophosphamide increased the incidence markedly and there was a wide inter-animal variability in the response (10-40 MPEs/1000 PEs). The paint-brush technique is considered technically simpler and recommended over the smear technique. This study shows that MPEs can be accurately scored in the bone-marrow of the rate provided due consideration is given to staining and sample size of PEs analysed per animal.

Animals

Mammalian male germ cell cytogenetics.

The methods used for the detection of chemically induced chromosome damage in male germ cells are discussed. These tests have been divided into direct and indirect cytogenetic methods. The direct methods assess chromosome damage in the dosed animal but analysis is restricted to the dividing spermatogonia and spermatocytes. Using indirect methods, chromosome damage is assessed in the F1 progeny of the dosed male and analysis covers all germ cell stages. Both methods can provide evidence of germ cell exposure but the data obtained from the indirect tests are considered more relevant since a positive result clearly constitutes unequivocal evidence of transmitted damage. The analysis of one-cell embryos from matings involving dosed parents is considered to be the most useful indirect test system since both structural and numerical aberrations in male and female F1 offspring can be assessed. Although relevant to the assessment of mutagenic hazard, the technically demanding methods used in the germ cell techniques prevent their use for preliminary screening programmes.

Animals

Sodium fluoride and chromosome damage (in vitro human lymphocyte and in vivo micronucleus assays).

The clastogenic potential of sodium fluoride was determined both in vitro (using cultured human lymphocytes) and in vivo (using the rat bone-marrow micronucleus test). The incidence of chromosome aberrations in human lymphocyte cultures exposed to 20 or 40 micrograms/ml sodium fluoride (3 and 9% respectively) was significantly increased compared with control cultures (0.5%). However, the incidence of micronucleated polychromatic erythrocytes in male AP rats dosed 1000 mg/kg NaF (the maximum tolerated dose over 24 h) or 500 mg/kg NaF was similar to that in the animals dosed distilled water (vehicle control). Thus, sodium fluoride is clastogenic in vitro but not in vivo.

Cells, Cultured

The mutagenic activity of razoxane (ICRF 159): an anticancer agent.

The mutagenic activity of razoxane (ICRF 159) was studied using the Salmonella/microsome assay and rodent bone-marrow micronucleus and metaphase assays. Razoxane (up to 5000 micrograms/plate) did not cause an increase in the mutation frequency in the Salmonella/microsome assay. In the mouse micronucleus assay razoxane (200 and 400 mg kg-1 i.p.) was cytotoxic to the bone marrow cells (which limited the analysis) but an increase in micronucleated polychromatic erythrocytes was observed in razoxane dosed animals (5-fold compared to control value). In the Chinese hamster metaphase assay razoxane (up to 500 mg kg-1 orally) induced abnormal chromosome condensation and an increase in structural chromosome aberrations (7 fold compared to control value) as well as an increase in the number of polypoid cells (8-fold compared to control value). The mutagenic effect of razoxane was restricted to eukaryotic organisms and was associated with specific chromosomal changes.

Animals

The use of fertilised mouse eggs in detecting potential clastogens.

Male mice were treated with methyl methanesulphonate (MMS) and then serially mated to females in oestrus, over the whole of the spermatogenic cycle. Chromosome preparations were made from fertilised eggs obtained from the matings and cultured overnight in the presence of a mititic inhibitor. No chromosomally abnormal eggs were found in matings using untreated animals but matings involving MMS-treated males produced a variety of abnormalities. The most sensitive stage in the spermatogenic cycle was 8 days after treatment, corresponding to the testicular sperm stage of spermatogenesis. At this sampling time 97% of the eggs analysed were chromosomally abnormal and the aberrations detected were predominantly 'shattered' male chromosomes. The aberration frequency in the post-meiotic stages decreased steadily up to day 20. No further structural chromosome aberrations were detected, until day 48, when chromosome fragments were detected in 2 eggs (4%) indicating that pre-meiotic damage can be induced and transmitted. The low background frequency obtained with the procedures used in this study enhances the sensitivity of the system for experimentally assessing the effects of clastogenic agents on male and female germ cells.

Animals

Mouse alcohol dehydrogenase isozymes: products of closely localized duplicate genes exhibiting divergent kinetic properties.

Electrophoretic variants for the stomach isozyme (ADH-C2) and liver isozyme (ADH-A2) of alcohol dehydrogenase in strains of Mus musculus have been used in genetic analyses to demonstrate close linkage between the structural genes (Ahd-3 and Adh-1, respectively) encoding these enzymes. No recombinants were observed between these loci among 126 backcross animals, which places them less than 0.8 centimorgans apart. Previous studies have positioned Adh-3, and a temporal locus (ADh-3t), on chromosome 3 (Holmes, "79; Holmes et al., "80). Kinetic analyses on partially purified preparations of these isozymes have demonstrated widely divergent catalytic properties and inhibitor specificities. The liver isozyme exhibited Michaelis constants that were nearly 3 orders of magnitude lower than the stomach isozyme for various alcohol and aldehyde substrates. Moreover, aminopropyl pyrazole strongly inhibited ADH-A2 (Ki=1.2M), whereas ADH-C2 was insensitive to inhibition under the conditions used. It is proposed that Adh-1 and Adh-3 are products of a recent gene duplication event during mammalian evolution and that considerable divergence in the active sites of these enzymes and the "temporal" genes controlling loci expression in differentiated tissues has subsequently occurred.

Alcohol Dehydrogenase