Oxidative stress parameters in plasma of Huntington's disease patients, asymptomatic Huntington's disease gene carriers and healthy subjects : a cross-sectional study.

BACKGROUND: Animal data and postmortem studies suggest a role of oxidative stress in the Huntington's disease (HD), but in vivo human studies have been scarce. AIM: To assess the presence of oxidative stress in HD patients and its occurrence relative to clinical symptoms. METHODS: Oxidative stress markers were determined in plasma of HD patients (n = 19), asymptomatic HD gene carriers (with > 38 CAG repeats) (n = 11) and their respective sex and agematched healthy controls (n = 47 and n = 22) in a cross-sectional study. RESULTS: With adjustment for age and sex, HD patients had higher plasma lipid peroxidation (LP) levels (ratio 1.20, 95% CI 1.09 to 1.32, p < 0.001) and lower reduced glutathione (GSH) levels (ratio 0.72, CI 0.55 to 0.94, p = 0.011) than their age and sex-matched controls. Although considerably younger, HD gene carriers did not differ from HD patients regarding LP and GSH levels, and had higher plasma LP (ratio 1.16, CI 1.02 to 1.32, p = 0.016) and lower GSH than their matched controls (ratio 0.73, CI 0.5 to 1.05). They had higher LP (ratio 1.18, CI 1.02 to 1.34, p = 0.019) and lower GSH (ratio 0.75, CI 0.51 to 1.11) than the healthy subjects matched to HD patients. CONCLUSIONS: Oxidative stress is more pronounced in HD patients and asymptomatic HD gene carriers than in healthy subjects. Differences in plasma LP and GSH are in line with the brain findings in animal models of HD. Data suggest that oxidative stress occurs before the onset of the HD symptoms.

Protein carbonylation and glycation in human lenses.

It has been observed protein carbonylation and glycation in the lens epithelial cell fractions of lenses in people with mature cataract. We used lenses of diabetic patients, weak and strong cigarette smokers and people who had senile cataract. The protein glycation is the highest in a diabetic senile cataract patients and the lowest in non-diabetic senile cataract patients. The protein carbonylation is extremely high in mitochondrial epithelial cells of the strong cigarette smokers. These results show that the glycation and carbonylation of the human lens proteins are the part of the cataract development in people. Specific factors, such as high glucose in diabetes and the tobacco smoke (in cigarette smokers), can change the lens structure, thus stimulating cataract development.

Alloxan induced cataract in a rat.

We have measured lipid peroxidation and the activity of antioxidant enzymes in lenses of alloxan injected rats. After 12 weeks alloxan treated rats developed lens cataract. Diabetes rats had both lower lens weight and lower level of proteins in soluble fraction of lens homogenate. Alloxan treatment is associated with a significant increase of thiobarbituric acid reactive substances and the activity of antioxidant enzymes superoxide dismutase and catalase. However, diabetes decreased the activity of glutathione peroxidase in rat lenses. These results show that alloxan, which changes antioxidant status in rat lenses, may cause complications associated with diabetes.

Behavioral treatments for adult dental avoidance. A stepped-care approach.

The growing research literature dealing with the psychologic treatment of dental fear and avoidance suggests several interventions as effective, but provides little guidance in choosing among them. Under these circumstances, experienced psychologic practitioners may choose among these interventions on the basis of their own clinical impressions as to which treatment might be best suited to each patient they see. An alternative approach is the stepped-care approach in which the least expensive/most practical intervention is implemented, with more costly or complex procedures implemented only if the less expensive intervention proves unsuccessful. Each of the behavioral treatments for dental fear that has received researchers' attention is briefly described, and they are ordered in terms of their costs in professional time. Finally, an account of the special precautions needed to implement a stepped-care strategy for the reduction of dental fear is outlined.

Effect of dexamethasone on glycogen deposition in pregnant rats and their fetuses.

Glycogen deposition was determined in pregnant rats and their fetuses twenty four hrs after maternal treatment with dexamethasone in the final days of pregnancy. Dexamethasone increases glycogen accumulation in the fetal liver, heart, adrenal glands and thymus. Simultaneously, it increases the glycogen concentration in maternal liver. In this study, dexamethasone did not change the glycogen level in the fetal kidneys, brain, placenta, lung and maternal adrenal glands. These results show that dexamethasone accelerated glycogen deposition in some fetal tissues. It is possible that dexamethasone activated enzymes of glycogen synthesis or potentiated the action of fetal corticosterone on induction of glycogen accumulation in fetal rat tissues.

Inhibiting effects of hypervitaminosis A on development of fetal rat adrenal glands.

Administration of pregnant rats with excess amounts of vitamin A from the 8th to the 10th day of pregnancy induced destruction in fetal brain. On the last day of pregnancy, fetuses of treated mothers have smaller weight of adrenal glands as compared with intact fetuses. Maternal treatment with high amounts of vitamin A significantly reduced protein and nucleic acids levels and inhibited cell multiplication in fetal rat adrenal glands. Adrenal glands of fetuses from vitamin A treated mothers synthetized in vitro from 4-14C progesterone less amounts of radioactive 11-deoxycorticosterone, corticosterone, 18-hydroxy-11-deoxycorticosterone and aldosterone than adrenal glands of intact fetuses on the last day of intrauterine development. These results showed that maternal hypervitaminosis A depressed morphological and functional development of fetal rat adrenal glands on the last day of pregnancy.

Nucleic acids, glycogen deposition and adrenal gland steroidogenesis in rats with a pituitary mammotropic tumor (MtTF4).

Rats which have an excess of ACTH, growth hormone and prolactin from a pituitary mammotropic tumor (MtT) show a marked growth of adrenal glands, liver, spleen and kidneys. Protein, DNA, RNA and cell numbers were increased in liver, adrenal glands, spleen and decreased in thymus of tumor bearing rats as compared to intact rats. MtT tumor decreased glycogen deposition in liver, adrenal glands, thymus and pituitary of MtT tumor bearing rats. Adrenal glands of intact and MtT tumor bearing rats incubated in vitro with 4-14C progesterone synthetized radioactive 11-deoxycorticosterone, corticosterone, 18-hydroxy-11-deoxycorticosterone, 18-hydroxy-corticosterone, 11-dehydro-corticosterone and aldosterone. Intact adrenals synthetized in vitro per mg tissues 60% higher amount of corticosteroids than adrenal glands of MtT tumor bearing rats. These results show that pituitary hormones from MtT tumor have multicellular effects. They increased nucleic acid content, cell multiplication and depressed steroid hydroxylation in adrenal mitochondria and glycogen deposition in some tissues of MtTF4 rats.

The effects of dexamethasone on nucleic acid synthesis and cell numbers in rat fetuses.

Pregnant rats were treated with dexamethasone in drinking water (10 micrograms/ml) from the 15th to the 22nd day of pregnancy. Dexamethasone significantly depressed cell numbers in fetal rat adrenal glands, liver, lung, testes and pituitary from the 17th to the 22nd day of pregnancy. These data indicated that dexamethasone retarded cell multiplication in rat fetuses. Weight per cell and protein per cell were less in fetal adrenal glands, kidneys and pituitary after treatment with dexamethasone. Dexamethasone had no effect on RNA per cell in various fetal tissues. The nucleic acid synthesis in vitro from 3H-thymidine and 3H-uridine were reduced in all observed fetal tissues after dexamethasone treatment on the 22nd day of pregnancy. These results show that dexamethasone has a multisystemic effect on fetal rat development, depressing nucleic acid synthesis and depleting cell numbers and cell size in various fetal tissues.

Characteristics of clients seeking therapy for the reduction of dental avoidance: reactions to pain.

Avoidant dental patients responding to advertisements offering behavioral treatment for avoidance of dentistry were compared with patients particularly low in dental fear along a number of dimensions. Factors which discriminated between the two groups were: gender; the neuroticism scale of the Eysenck Personality Inventory; several self-reported reactions to past dental treatment; tolerance for dental (but not non-dental) pain; state anxiety during pain testing; and a measure of "efficacy". This last finding suggested that avoidant subjects saw themselves as less able to tolerate electrical tooth pulp stimulation and dental treatment than did their fearless counterparts, but no different in ability to tolerate pain irrelevant to dentistry (shock to the forearm).

Influence of dexamethasone on growth and development of rat fetuses: changes in nucleic acids and protein content.

Pregnant rats were treated with dexamethasone in drinking water (10 micrograms/ml) from the 15th to the 22nd day of pregnancy. Dexamethasone significantly reduced the weight of rat fetuses and concentration of DNA, RNA and proteins in fetal adrenal glands, liver, placenta, brain, kidneys, heart, lung, testes and pituitary from the 17th to the 22nd day of pregnancy. These data show that dexamethasone given to pregnant rat may lead to potentially deleterious effects on fetal rat development.

Treatment of an overactive gag reflex: two cases.

Two cases are presented in which avoidance of dental work was caused by an overactive gag reflex rather than fear. Subjects were able to demonstrate increased control of gagging in the laboratory, and to complete a series of dental visits immediately after treatment and again at 6 or 12 month follow-up. Assessment and treatment strategies which were developed with these subjects are described.

Influence of ACTH secreting tumor (MtTF4) on fetal rat adrenal gland steroidogenesis in vitro in prolonged pregnancy.

Pregnant female rats with ACTH secreting tumor (MtTF4) have prolonged pregnancy and cannot deliver. The fetuses of tumor bearing females have in prolonged pregnancy on days 24 and 25 of pregnancy greater body weight and smaller adrenal weight as compared to intact fetuses of the 22nd day of pregnancy. The fetal adrenal glands converted to vitro 4-14C progesterone to radioactive 11-deoxycorticosterone (DOC), corticosterone (B), 18-hydroxy-11-deoxycorticosterone (18-OH-DOC), 18-hydroxy-corticosterone (18-OH-B) and aldosterone. Fetal adrenal glands in prolonged pregnancy synthetized in vitro less amount of radioactive DOC, B and 18-OH-DOC. A negative relationship exists between the maternal corticosterone which passes the placenta to fetuses and corticosteroidogenesis of fetal adrenal glands. These results indicate the possibility that fetal rat adrenal glands with their corticosteroids participate in pregnancy and influence normal delivery.

Fetal rat adrenal gland steroidogenesis in vitro in prolonged pregnancy.

Progesterone, injected into pregnant rats on the last days of pregnancy, prolonged pregnancy and prevented parturition. The fetuses from mothers whose pregnancies were prolonged have greater body and adrenal weights on days 23 and 24 of gestation as compared with 1- and 2-day-old rats. The adrenal glands of fetuses and neonatal rats converted in vitro 4-(14)C-progesterone to 11-deoxycorticosterone (DOC), corticosterone (B), 18-hydroxy-11-deoxycorticosterone (18-OH-DOC), 18-hydroxy-corticosterone (18-OH-B) and aldosterone. The fetal adrenal glands on the 23rd and 24th day of pregnancy synthesized in vitro less DOC, corticosterone and 18-OH-DOC than the adrenal glands of intact neonatal rats. These results demonstrated that progesterone in prolonged pregnancy inhibited enzymes of steroid hydroxylation which converted progesterone to DOC, corticosterone and 18-OH-DOC in fetal rat adrenal glands.

Reactions to pain among subjects high and low in dental fear.

Differential pain tolerance might account for the diversity of reactions commonly seen in response to stressful medical and dental procedures. College students reporting themselves either highly fearful or nonfearful of dental work were compared in several aspects of their reactions to dental and nondental pain. The two groups did not differ in pain threshold or pain tolerance assessed during tooth pulp stimulation or during electrical stimulation of the forearm. High-dental fear subjects, however, retrospectively rated tooth shock (but not arm shock) more painful than low-fear subjects. High-fear subjects also showed significantly greater affective reactions assessed via the Anxiety Differential during both tolerance tests, with the group differences greater in magnitude during tooth shock than arm shock.

Reports of pain after dental treatment, electrical tooth pulp stimulation, and cutaneous shock.

A growing body of literature suggests that pain is a crucial factor in the development and maintenance of apprehension toward dental treatment. These findings are often at variance with dental practitioners' impressions that routine dental treatment is virtually painless. Data from this study suggest that routine dental treatment is seldom perceived by regular patients as painless but is seen as low in intensity of pain compared with mild laboratory stressors. These data are interpreted as supporting the hypothesis that dental treatment is relatively painless. However, this conclusion conflicts with data supporting the importance of pain in dental fear, and possible reasons for the discrepancy are presented.

Fetal rat adrenal growth and steroidogenesis in vitro after maternal dexamethasone treatment.

Two groups of female rats were treated with dexamethasone phosphate (DEX) for 24 h. One group received DEX in drinking water (10 micrograms/ml) on the 15th day of pregnancy (DEX15--16), and the second group on the 17th day of pregnancy (DEX 17--18). The mothers and fetuses were sacrificed on the 20th and 22nd days of pregnancy. DEX reduced adrenal weights and concentration of corticosterone in plasma of the treated females and their fetuses. Fetal body weight was also reduced. However, the lightest adrenal glands were found in fetuses of the DEX17--18 mothers. Furthermore, the 19-day-old fetuses belonging to the DEX17--18 mothers had smallest amounts of corticosterone in plasma, and in plasma, and their adrenal glands produced the lowest amounts of radioactive corticosterone, 11-doxycorticosterone and 18-hydroxy-11-deoxycorticosterone from 4-14C progesterone after 1 h or incubation in vitro. In the 21-day-old fetuses belonging to both the groups of treated mothers, the production of steroids by the adrenal glands was similar and to the same extent reduced in comparison to the control fetuses.