Oxidative stress in benign prostate hyperplasia

To assess the status of oxidative stress in benign prostate hyperplasia, a very common disease in older men which constitutes a public health problem in Jijel, prostate tissues were obtained by transvesical adenomectomy from 10 men with benign prostate hyperplasia. We measured the cytosolic levels of malondialdehyde (MDA) and glutathione (GSH) and cytosolic enzyme activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione S‐transferase. The development of benign prostate hyperplasia is accompanied by impaired oxidative status by increasing levels of MDA, depletion of GSH concentrations and a decrease in the activity of all the antioxidant enzymes studied. These results have allowed us to understand a part of the aetiology of benign prostate hyperplasia related to oxidative stress.     

The role of personality, coping style and social support in health-related quality of life in HIV infection

Objective: To determine the role of health status, personality and coping style, on self-report health-related quality of life (QoL). Methods: Participants were HIV seropositive individuals at all disease stages from three samples (a) gay/bisexual men from the UK, (b) injecting drug users from the UK, (c) injecting drug users from Italy. All participants completed questionnaires evaluating QoL, personality, coping style and social support. Explicit models of the relationships between the measured variables based on a review of the literature were tested using structural equation modelling. Results: Health status was modestly associated with the physical but not the psychological aspects of QoL ( = 0.44). Neuroticism was strongly associated with psychological QoL ( = –0.73) but only weakly with physical QoL ( = –0.21). The samples did not differ in either the pattern or the magnitude of these relationships. Mediating factors such as coping style, social support and other personality variables had only a weak influence on the role of Neuroticism. Conclusions: Neuroticism had a strong influence on health-related QoL that was independent of health status. Neuroticism was more strongly associated with the psychological aspects of QoL than health status. Coping styles and the other psychological variables assessed had only a weak mediating influence on this relationship.     

Vitamin D metabolism impairment in the rat’s offspring following maternal exposure to <Superscript>137</Superscript>cesium

Previous works clearly showed that chronic contamination by ¹³⁷cesium alters vitamin D metabolism. Since children are known to be a high-risk group for vitamin D metabolism disorders, effects of ¹³⁷Cs on vitamin D biosynthetic pathway were investigated in newborn rats. The experiments were performed in 21-day-old male offspring of dams exposed to ¹³⁷Cs in their drinking water at a dose of 6,500 Bq/l (150 Bq/rat/day) during the lactation period. Significant modifications of blood calcium (−7%, P < 0.05), phosphate (+80%, P < 0.01) and osteocalcin (−25%, P < 0.05) levels were observed in contaminated offspring, associated with an increase of blood vitamin D₃ (+25%, P < 0.01). Besides, decreased expression levels of cyp2r1 and cyp27b1 (−26 and −39%, respectively, P < 0.01) were measured in liver and kidney suggesting a physiological adaptation in response to the rise in vitamin D level. Expressions of vdr, ecac1, cabp-d28k, ecac2 and cabp-9k involved in renal and intestinal calcium transport were unaffected. Altogether, these data show that early exposure to post-accidental doses of ¹³⁷Cs induces the alteration of vitamin D metabolism, associated with a dysregulation of mineral homeostasis.     

Oxysterol stimulation of epidermal differentiation is mediated by liver X receptor-beta in murine epidermis

Liver X receptor-alpha and -beta are members of the nuclear hormone receptor superfamily that heterodimerize with retinoid X receptor and are activated by oxysterols. In recent studies we found that treatment of cultured human keratinocytes with oxysterolstimulated differentiation, as demonstrated by increased expression of involucrin and transglutaminase, and inhibited proliferation. The aims of this study were to determine: (i) whether oxysterols applied topically to the skin of mice induce differentiation in normal epidermis; (ii) whether this effect is mediated via liver X receptor-alpha and/or liver X receptor-beta; and (iii) whether oxysterols normalize epidermal morphology in an animal model of epidermal hyperplasia. Topical treatment of normal hairless mice with 22(R)-hydroxycholesterol or 24(S),25-epoxycholesterol resulted in a decrease in epidermal thickness and a decrease in keratinocyte proliferation assayed by proliferating cell nuclear antigen staining. Moreover, oxysterol treatment increased the levels of involucrin, loricrin, and profilaggrin protein and mRNA in the epidermis, indicating that oxysterols stimulate epidermal differentiation. Additionally, topical oxysterol pretreatment improved permeability barrier homeostasis. Whereas liver X receptor-alpha-/- mice revealed no alterations in epidermal differentiation, the epidermis was thinner in liver X receptor-beta-/- mice than in wild-type mice, with a reduced number of proliferating cell nuclear antigen positive cells and a modest reduction in the expression of differentiation markers. Topical oxysterol treatment induced differentiation in liver X receptor-alpha-/- mice whereas in liver X receptor-beta-/- mice there was no increase in the expression of differentiation markers. Whereas both liver X receptor-alpha and liver X receptor-beta are expressed in cultured human keratinocytes and in fetal rat skin, only liver X receptor-beta was observed on northern blotting in adult mouse epidermis. Finally, treatment of hyperproliferative epidermis with oxysterols restored epidermal homeostasis. These studies demonstrate that epidermal differentiation is regulated by liver X receptor-beta and that oxysterols, acting via liver X receptor-beta, can induce differentiation and inhibit proliferation in vivo. The ability of oxysterols to reverse epidermal hyperplasia suggests that these agents could be beneficial for the treatment of skin disorders associated with hyperproliferation and/or altered differentiation.     

Chronic contamination with 137Cesium affects Vitamin D3 metabolism in rats

Twenty years after Chernobyl disaster, many people are still chronically exposed to low dose of (137)Cs, mainly through the food consumption. A large variety of diseases have been described in highly exposed people with (137)Cs, which include bone disorders. The aim of this work was to investigate the biological effects of a chronic exposure to (137)Cs on Vitamin D(3) metabolism, a hormone essential in bone homeostasis. Rats were exposed to (137)Cs in their drinking water for 3 months at a dose of 6500 Bq/l (approximately 150 Bq/rat/day), a similar concentration ingested by the population living in contaminated territories in the former USSR countries. Cytochromes P450 enzymes involved in Vitamin D(3) metabolism, related nuclear receptors and Vitamin D(3) target genes were assessed by real time PCR in liver, kidney and brain. Vitamin D, PTH, calcium and phosphate levels were measured in plasma. An increase in the expression level of cyp2r1 (40%, p<0.05) was observed in the liver of (137)Cs-exposed rats. However a significant decrease of Vitamin D (1,25(OH)D(3)) plasma level (53%, p=0.02) was observed. In brain, cyp2r1 mRNA level was decreased by 20% (p<0.05), while the expression level of cyp27b1 is increased (35%, p<0.05) after (137)Cs contamination. In conclusion, this study showed for the first time that chronic exposure with post-accidental doses of (137)Cs affects Vitamin D(3) active form level and induces molecular modifications of CYPs enzymes involved its metabolism in liver and brain, without leading to mineral homeostasis disorders.     

Effects of depleted uranium after short-term exposure on vitamin D metabolism in rat

Uranium is a natural radioactive heavy metal. Its toxicity has been demonstrated for different organs, including bone, kidney, liver and brain. Effects of an acute contamination by depleted uranium (DU) were investigated in vivo on vitamin D₃ biosynthetic pathway. Rats received an intragastric administration of DU (204 mg/kg) and various parameters were studied either on day 1 or day 3 after contamination. Cytochrome P450 (CYP27A1, CYP2R1, CYP27B1, CYP24A1) enzymes involved in vitamin D metabolism and two vitamin D₃-target genes (ECaC1, CaBP-D9K) were assessed by real time RT-PCR in liver and kidneys. CYP27A1 activity was measured in liver and vitamin D and parathyroid hormone (PTH) level were measured in plasma. In acute treated-rats, vitamin D level was increased by 62% and decreased by 68% in plasma, respectively at day 1 and at day 3, which paralleled with a concomitant decrease of PTH level (90%) at day 3. In liver, cyp2r1 mRNA level was increased at day 3. Cyp27a1 activity decreased at day 1 and increased markedly at day 3. In kidney, cyp27b1 mRNA was increased at days 1 and 3 (11- and 4-fold respectively). Moreover, ecac1 and cabp-d9k mRNA levels were increased at day 1 and decreased at day 3. This work shows for the first time that DU acute contamination modulates both activity and expression of CYP enzymes involved in vitamin D metabolism in liver and kidney, and consequently affects vitamin D target genes levels.     

Placental expression of the nuclear receptors for oxysterols LXRalpha and LXRbeta during mouse and human development

Ontogenesis and localization expression of genes encoding for the nuclear receptors for oxysterols (lxralpha and lxrbeta) were investigated in human and mouse placenta during gestation. Both mRNAs were detectable in the placentation throughout the gestation (from 7 days postcoitum and 6th week of gestation in mouse and human, respectively) by Northern blots or RT-PCR experiments. Lxralpha showed a higher accumulation in the mouse yolk sac. In situ hybridization pointed a specific expression of lxralpha in the human amniotic membranes.