Chromosomal investigations in children with pyknolepsy on dipropylacetate monotherapy

Summary We analyzed chromosome preparations obtained from leukocytes of ten children with pyknolepsy and treated with dipropylacetate (DPA) as monotherapy. Structural or numerical aberrations were not found more frequently in our patients than in five normal children (control group).     

Chromosomal damage in chronic alcohol users

Summary First in vitro mitoses were analysed from the peripheral leukocytes of 22 chronic alcohol users and of 18 controls. The frequency of exchange aberrations of the chromatid and chromosome type were significantly higher in the alcohol as compared with the control group. The results indicate an indirect or direct mutagenic activity of alcohol in vivo.

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Zusammenfassung Erste in vitro-Mitosen peripherer Leukocyten von 22 Alkoholikern und 18 Kontrollen wurden untersucht. Die Häufigkeiten von Austauschaberrationen vom Chromatiden und Chromosomentyp sind bei den Alkoholikern signifikant höher als bei den Kontrollen. Die Ergebnisse weisen auf eine indirekte oder direkte mutagene Wirkung von Alkohol in vivo hin.

     

Chromosomal damage in chronic alcohol users.

First in vitro mitoses were analysed from the peripheral leukocytes of 22 chronic alcohol users and of 18 controls. The frequency of exchange aberrations of the chromatid and chromosome type were significantly higher in the alcohol as compared with the control group. The results indicate an indirect or direct mutagenic activity of alcohol in vivo.     

Chromosomal damage induced by caprolactam in human lymphocytes

Caprolactam was tested in the in vitro human lymphocyte cytogenetic assay both in the presence and absence of S9 mix at dose levels up to 5500 micrograms/ml using lymphocytes obtained from a male donor and in the presence of S9 mix using lymphocytes obtained from a female donor. Statistically significant increases in chromosomal damage were observed at 5500 micrograms/ml dose level in cells from both donors. This positive response was enhanced by the inclusion of chromosomal gaps in the calculations. It was concluded that caprolactam induces chromosomal damage in human lymphocytes in vitro albeit at comparatively high dose levels.     

Chromosomal damage as prognosis marker in cervical carcinogenesis

Cancer of the uterine cervix is the third most common cancer in women worldwide and the most common cancer among Mexican and Latin American women. Risk factors that have been associated with the development of cervical intraepithelial neoplasia suggest that Human Papillomavirus (HPV) types 16, 18, 31, and 33 entail a high risk of developing a malignancy of this type. The accumulation of genetic alterations allows the growth of neoplastic cells; chromosomal instability is an event that occurs in the precancerous stages. The candidate cancer risk biomarkers include cytogenetic endpoints, such as chromosomal aberrations, sister chromatid exchange, micronuclei, and the outcomes of comet assay and DNA breakage detection-fluorescence in situ hybridization. The patterns identified in these cytogenetic studies indicate that chromosomal instability is a transient and chromosomally unstable intermediate in the development of cervical lesions. In this context, the mechanisms that may underlie the progressive increase in genetic instability in these patients seem to be related directly to HPV infection. The studies discussed in this paper show that chromosomal instability may serve as a biomarker by predicting the progression of cervical intraepithelial neoplasia. Nevertheless, these results should be validated in larger, prospective studies.     

Effects of add-on melatonin on sleep in epileptic children on carbamazepine monotherapy: A randomized placebo controlled trial

Sleep and Biological Rhythms - This double-blind, randomized, placebo controlled study in epileptic children, aged 3–12 years, evaluated the effect of add-on melatonin on the sleep behavior...     

Rapid thin-layer chromatographic method for the simultaneous determination of carbamazepine,diphenylhydantoin, mephenytoin,phenobarbital and primidone in serum

A thin-layer chromatographic method for the simultaneous determination of five anticonvulsant drugs is presented. The serum is extracted with toluene and the dried extract is dissolved in chloroform and applied on to a thin-layer chromatographic plate. After development, the plate is scanned at 215 nm without staining. The drug peaks are well defined. Most of the interfering substances that occur naturally in serum are soluble in and eliminated by the liquid front.     

Teratogenic effects of dosage levels and time of administration of carbamazepine, sodium valproate, and diphenylhydantoin on craniofacial development in the CD-1 mouse fetus

The objective of this investigation was to study the teratogenic effects of dosage levels and time of administration of three anticonvulsant drugs (carbamazepine [CMZ], sodium valproate [NaV], and diphenylhydantoin [DPH]) on craniofacial development in the CD-1 mouse fetus. Pregnant females were intubated on each of days 8-10, 11-13, 14-16, and 8-16 of gestation with the following dose levels for each drug: 375, 563, 938 mg/kg CMZ; 225, 338, 563 mg/kg NaV; 50, 75, 125 mg/kg DPH. Appropriate control groups were maintained for each drug. On gestation day 17, pregnant females were killed and implantation sites were recorded as live, dead, or resorbed. All live fetuses were examined for craniofacial defects. Results of examination of 1,398 fetuses indicated that CMZ, NaV, and DPH were teratogenic and embryotoxic at all dose levels. This study indicated that the observed decrease in mean fetal weight was drug-, dose-, and time-dependent. There was a drug-, dose-, and time-dependent increase observed in the number of dead fetuses, whereas the number of resorbed fetuses was observed to be only time-dependent. The observed frequencies of hydrocephalies, secondary palatal clefts, and submucous palatal clefts were significant for all three factors (drug, dose, and time) whereas the observed frequencies of hematomas and exencephalies were significant only for drug and time. Cleft lips were observed only in the highest dose level of DPH. Uterine horn distribution of defects indicated that fetuses located at the proximal end of the horns were less subject to major defects than those fetuses located at the distal end of the uterine horns. Fetuses with craniofacial hematomas were found in the proximal one-third of the uterine horn, resorbed fetuses, and fetuses with submucous palatal clefts in the middle one-third of the uterine horns and dead fetuses and fetuses with exencephalies, cleft lips, and secondary palatal clefts were localized in the distal one-third of the uterine horns. In comparing the effect of drug, dosage, and time on the development of craniofacial malformations in the CD-1 mouse fetus, CMZ was the least teratogenic and embryotoxic of the three anticonvulsant drugs employed in this study.     

Chromosomal damage induced by maleic hydrazide in mammalian cells in vitro and in vivo

The induction of sister-chromatid exchanges (SCE) and chromosomal aberrations (Ch.Ab.) by the herbicide maleic hydrazide (MH) has been investigated in Chinese hamster ovary (CHO) cells grown in vitro and in bone marrow cells of mice treated in vivo. MH induces SCE and Ch.Ab. in CHO cells without metabolic activation; however, no induction of SCE was found in the in vivo experiments.     

A teratogenicity study on hydroxyurea and diphenylhydantoin in cats

Hydroxyurea, an antitumor drug and known teratogen in rat, miniature swine and dog, and diphenylhydantoin, a teratogen in mouse and rat, were assessed for teratogenic effects in cat. Pregnancies were induced, by synchronizing gonadotropin-stimulated estrus and ovulation with natural copulations. Hydroxyurea at 50 or 100 mg/kg, and sodium diphenylhydantoin at 1 or 2 mg/kg dosages, were administered orally in single daily doses from gestation days 10-22. Appropriate controls given empty capsules, were included for each drug. Cats were necropsied on gestation day 43. Fetuses were examined for external, visceral and skeletal malformations. Hydroxyurea at 50 mg/kg dose produced a low teratogenic activity and at 100 mg/kg a high incidence of non-pregnancy and resorptions with, consequently, fewer live fetuses. Diphenylhydantoin gave no clear evidence of teratogenicity at any test dose but was embryolethal at the maternally toxic dose of 2 mg/kg. So far, studies conducted suggest that the cat is a useful species for screening drugs and chemicals for their teratogenic potential.     

Chromosomal damage induced in human lymphocytes by low doses of D-T neutrons

Unstable chromosome aberrations induced by in vitro irradiation with zero plus seven low doses of 14.8 MeV D-T neutrons in the range 3.55-244 mGy have been analysed in human peripheral blood lymphocytes. In order to obtain the required large numbers of scored cells for such low doses, fourteen laboratories participated in the experiment. The dose responses for dicentrics, excess acentrics and total aberrations, fitted well to the Y = alpha D model. The alpha coefficient of yield for dicentrics, 1.60 +/- 0.07 X 10(-2) Gy-1, compares well with the values obtained in previous studies with D-T neutrons at somewhat higher doses. Results from a previous collaborative study using 250 kVp X-rays over a comparable dose range indicated the possible existence of a threshold below 50 mGy. In the present study there is no clear evidence for neutrons for such a threshold. However, the data were insufficient to permit the rejection of a possible threshold below approximately 10 mGy.     

Chromosomal damage in peripheral blood lymphocytes of patients treated for testicular cancer

Summary We describe the presence of a large number of chromosome aberrations in lymphocytes of 50 patients with testicular cancer. These chromosomal aberrations were not only found in patients treated with chemotherapy but also in untreated patients or in patients after surgery alone. Our results suggest a role for genetic instability in the pathogenesis of testicular cancer. This instability might be a risk factor for the development of secondary malignancies.     

Chromosomal damage and apoptosis analysis in exfoliated oral epithelial cells from mouthwash and alcohol users

Chromosomal damage and apoptosis were analyzed in users of mouthwash and/or alcoholic beverages, using the micronucleus test on exfoliated oral mucosa cells. Samples from four groups of 20 individuals each were analyzed: three exposed groups (EG1, EG2 and EG3) and a control group (CG). EG1 comprised mouthwash users; EG2 comprised drinkers, and EG3 users of both mouthwashes and alcoholic beverages. Cell material was collected by gently scraping the insides of the cheeks. Then the cells were fixed in a methanol/acetic acid (3:1) solution and stained and counterstained, respectively, with Schiff reactive and fast green. Endpoints were computed on 2,000 cells in a blind test. Statistical analysis showed that chromosomal damage and apoptosis were significantly higher in individuals of groups EG1 and EG3 than in controls (p < 0.005 and p < 0.001, respectively). No significant difference in chromosomal damage and apoptosis was observed between the exposed groups. In EG2, only the occurrence of apoptosis was significantly higher than in the controls. These results suggest that mouthwashes alone or in association with alcoholic drinks induce genotoxic effects, manifested as chromosomal damage and apoptosis. They also suggest that alcoholic drinks are effective for stimulating the process of apoptosis. However, these data need to be confirmed in larger samples.     

Comparison between bretylium and diphenylhydantoin interaction with mucosal sodium-channels

The antifibrillatory drug bretylium and the antiepileptic drug diphenylhydantoin cause an increase in the potential different and in the short-circuit current (SCC) across frog skin when added to the outer surface. The effect of both drugs depends upon the presence of sodium ions in the outer medium and is blocked by the specific sodium channel blocker, amiloride. Quantitative analysis shows that amiloride binds to open as well as closed mucosal sodium channel with the same affinity. The effects of diphenylhydantoin and bretylium differ with respect to their dependence on external pH. The diphenylhydantoin or the bretylium stimulatory effects are additive to the effects of oxytocin. In most cases the diphenylhydantoin and bretylium effects are also additive. It is concluded that the external side of the mucosal Na+ channels contains sites which interact specifically with either bretylium or diphenylhydantoin and thus remove the sodium induced closure of the channels.     

Comparison of the teratogenic properties manifested in BALB c mice, by diphenylhydantoin and deuterated diphenylhydantoin

The aim of this study was to investigate the role of an arene oxide pathway in the teratogenicity displayed by DPH, a highly effective antiepileptic agent. This approach was carried out by comparing the teratogene potential of DPH and of p2-H-DPH administrated at days 8, 9 and 12 of gestation. The present findings support the hypothesis that substitution of protium by deuterium at the para position of one of the phenyl rings, which favours an arene oxide pathway, causes an increase in some to the teratogenic effects of DPH.