Analysis of DNA damage using the comet assay in infants fed cow's milk.

It has been hypothesized that non-human milk feeding may increase the risk for cancer or for a specific cancer or group of cancers as well as the risk for diseases such as type-1 diabetes mellitus and Crohn's disease. Regarding DNA damage leading to cancer development in the absence of human milk protection, a comparison between infants fed human milk and cow's milk has been performed. Each group consisted of 35 infants, whose ages ranged from 9 to 12 months. The level of DNA damage in the peripheral blood lymphocytes of infants has been studied by the comet assay. A significant increase has been found in the number of limited DNA-damaged (p < 0.001) and extensive DNA-damaged (p < 0.001) cells of infants fed cow's milk. To our knowledge, this is the first study using the comet assay on infants not breast-fed. Supporting our previous SCE study, these results suggest that there is some level of DNA damage in the lymphocytes of infants not breast-fed and this may lead to malignancy in childhood or later in life.

Antioxidant enzymes and lipid peroxidation in adolescents with inhalant abuse.

Glue and thinner sniffing is a serious medical problem since the volatile constituents of these substances can lead to severe damage to bone marrow, liver, kidney, brain, and heart. The exact mechanisms responsible for tissue and organ damage in children with inhalant abuse have not yet been determined. In this study, we aimed to determine the levels of antioxidant enzymes and malondialdehyde in children with inhalant abuse. Erythrocyte and plasma glutathione peroxidase (GSH-Px) activities, erythrocyte superoxide dismutase (SOD) activity, and erythrocyte and plasma malondialdehyde (MDA) levels were measured as biological markers of oxidative damage and lipid peroxidation in 37 glue and thinner (inhalant) abusers. The levels were compared with those of the 27 well-matched healthy adolescents. Erythrocyte SOD activity and erythrocyte and plasma MDA levels were significantly higher, whereas erythrocyte and plasma GSH-Px activities were significantly lower in children with inhalant abuse when compared to controls (p<0.01). These findings imply that chronic inhalation of volatile substances can alter the levels of antioxidant enzymes including SOD and GSH-Px, and can increase lipid peroxidation in adolescent abusers.

DNA damage in children treated with imipramine for primary nocturnal enuresis.

BACKGROUND: Despite the fact that primary nocturnal enuresis (PNE) is self-limited and pathologically benign, the emotional stress and inconvenience that it produces, warrants treatment. Imipramine is one of the widely used drugs in PNE treatment. Although some mutagenic effects were suggested in imipramine administration, this toxicity has never been investigated in enuretic patients. The aim of this study was to evaluate the association of exposure to imipramine with DNA damage. METHODS: Thirty-five children treated with imipramine for at least 4.5 months who were in otherwise good health were accepted into the investigation. Twenty healthy sisters or brothers of the patients who did not use any long-term drugs were studied simultaneously as the control group. Comet assay was used to evaluate DNA damage. RESULTS: Damaged (limited and extensive migrated) cells of the enuretic children who were taking imipramine were statically higher than that of the control group (P < 0.05) indicating a detectable DNA damaging effect of imipramine in human lymphocytes. CONCLUSIONS: Our finding suggests that the difference in comet scores between two groups was induced by the imipramine treatment. The other possibility to be considered is the psychological stress of the children who were concerned by the symptoms and their parent's anxiety. As our preliminary data were based on a limited number of children, further research is needed considering the importance of this possible toxic effects which may be associated with mutagenicity.

Selenium and zinc levels in volatile substance abusers.

Plasma and erythrocyte levels of selenium (Se) and zinc (Zn) have not been investigated in volatile (inhalant) substance abusers previously, although changes in the activities of antioxidant enzymes resulting from oxidative damage caused by various constituents of volatile substances have been shown in a few animal and human studies. Concentrations of these two elements in erythrocytes and plasma of 37 adolescents with inhalant abuse were measured by atomic absorption spectrophotometry and compared with those of 37 age-matched healthy controls. Erythrocyte and plasma levels of Se and plasma level of Zn were significantly lower in the study group when compared to the control group. Chronic inhalation of volatile substances can decrease the plasma levels of Se and Zn and, thus, may lead to a decrease in the activity of antioxidant enzyme systems in adolescent abusers. The role of Se and Zn supplementation in children with inhalant abuse remains to be determined considering the reduced antioxidant activity resulting from deficiency of these trace elements.

The use of the corpus cavernosum for the administration of phenobarbital: an experimental study in dogs.

Status epilepticus (SE) is classically defined as a generalized tonic-clonic seizure lasting longer than 30 min. Prolonged seizure activity can be resulted in irreversible cerebral injury. In addition, the existence evidence suggests that the longer the duration of the seizure activity is less likely to be controlled. The intravenous (IV) access is frequently difficult during SE, especially in infants and neonates. On the other hand, it has been demonstrated that high volumes of fluid can be injected into the corpora cavernosa. In this study, phenobarbital (PB) was administered to dogs using both IV and intracavernous (IC) routes with a dose of 20 mg/kg. The time period required to establish the IC route was less than 5 s. The levels of PB in the blood were measured and all results were compared. There was no statistically significant difference between the IV and IC administration with regard of the blood PB levels. Within 48 h of the experiment, none of animals demonstrated any evidence of infection or disability. Our findings suggest that the IC route may be an alternative route for the administration of PB when venous access is not immediately available or if it is not possible to achieve.

Preliminary study on DNA damage in non breast-fed infants.

BACKGROUND: There are many advantages of human milk for infants, including protection against cancer development and the advantages have been emphasized in several studies. In this study, infants fed by human milk has been compared with those fed by cow's milk concerning DNA damage. METHODS: The level of genetic damage in the peripheral blood lymphocytes of infants who were fed mainly by cow's milk and breast milk has been studied by sister chromatid exchange (SCE) analysis, which is a sensitive measurement of chromosomal damage. Each group consisted of 30 infants, whose ages ranged from 9 to 12 months. RESULTS: A significant increase (P < 0.0001) was found in the frequencies of SCE of infants not breast-fed (n = 30, mean SCE/cell +/- SD: 8.66 +/- 1.15) compared to those who were breast-fed (n = 30, mean SCE/cell +/- SD: 4.93 +/- 0.82). CONCLUSION: To our knowledge, there has been no published study investigating SCE ratio regarding DNA damage in infants not breast-fed. Molecular mechanism of DNA damage caused by the absence of human milk protection is a subject of future investigations.

Intracavernous application of diazepam: an alternative route of the seizure treatment--an experimental study in rabbits.

BACKGROUND: There is a general need to terminate seizures as soon as possible using anticonvulsant drugs via an intravenous (i.v.) route, but it is often difficult to achieve a secure i.v. line during the seizure, especially in children. However, it has been demonstrated that high volumes of fluid can be injected into the corpora cavernosa. The purpose of this study was to evaluate the absorption properties of diazepam (DZ) after intracavernous (i.c.) administration and whether therapeutically significant plasma concentrations can be obtained or not. METHODS: Diazepam was administered to rabbits using both the i.v. and i.c route with a dose of 1 mg/kg. Blood samples were collected from the saphenous vein for a time period of 30 min. The levels of DZ in the blood were analyzed by high performance liquid chromatography and their blood profiles were obtained and compared. RESULTS: The insertions of the needle using this method were successful in all cases. The average time of inserting the needle was less than 5 s. There was no statistically significant difference between the i.v. and i.c. administration with regard of the blood DZ levels. Within 48 h after the experiment, none of the animals demonstrated any evidence of infection or disability. CONCLUSION: Our results demonstrated that commercially available parenteral DZ can be absorbed rapidly by the i.c. route in rabbits. Further studies are needed on the feasibility of this method before it is evaluated in humans.