Chromaffin cells: the peripheral brain.

Chromaffin cells probably are the most intensively studied of the neural crest derivates. They are closely related to the nervous system, share with neurons some fundamental mechanisms and thus were the ideal model to study the basic mechanisms of neurobiology for many years. The lessons we have learned from chromaffin cell biology as a peripheral model for the brain and brain diseases pertain more than ever to the cutting edge research in neurobiology. Here, we highlight how studying this cell model can help unravel the basic mechanisms of cell renewal and regeneration both in the central nervous system (CNS) and neuroendocrine tissue and also can help in designing new strategies for regenerative therapies of the CNS.

Neurotransmitters of the non-adrenergic non-cholinergic relaxation of proximal stomach.

The proximal third of the stomach (fundus plus oral corpus) relaxes during swallowing so that it can hold large amounts of food with limited increases in intraluminal pressure. This mechanism has been called "receptive relaxation" and is mediated by a vago-vagal reflex. When the food bolus reaches the stomach, gastric relaxation is maintained by another reflex starting from mechanoreceptors in the gastric wall. This second mechanism has been named "adaptive relaxation" or "gastric accommodation" and involves both intramural and vagal reflex pathways, whose inhibitory neurons are always intramural. There was initially a great deal of controversy about the identity of the neurotransmitter/s released by inhibitory neurons, but at present nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) are considered to be the most likely candidates. Several lines of evidence indicate that adenosine triphosphate (ATP) might be implicated too. It seems that these neurotransmitters are co-released from the inhibitory motor neurons and are responsible for the different features of the NANC relaxation induced by low- or high-frequency neuronal firing. NO (and perhaps ATP) would be responsible for the rapid beginning and the initial rapid development of the relaxation evoked by neuronal firing at low- or high-frequency and VIP for the long duration of the relaxation evoked by high-frequency neuronal activation. This review will deal mainly with the physiological characteristics and pharmacological features of the NANC relaxation of the proximal stomach and the evidences favoring or excluding a role as inhibitory neurotransmitters of ATP, NO and VIP in different species.

Treatment of lacrimal stenoses obstructions with interventional radiology: immediate and 5-year follow-up results.

PURPOSE: This study was undertaken to evaluate the effectiveness of the Song stent in patients with nasolacrimal duct obstruction. MATERIALS AND METHODS: Between 2003 and 2007, we treated 76 consecutive nasolacrimal obstructions in 73 patients (mean age 56 years; range 19-81) with implantation of polyurethane stents. Indications were epiphora in 46 patients, dacryocystitis in 18 and recurrent conjunctivitis in three. Average follow-up was 1 year (3 months to 5 years). RESULTS: Technical success was achieved in 73 procedures (96%). Complications included pain in three cases, eyelid inflammation in four cases and severe bleeding in one case. Postprocedural mucocele was observed in five patients. Mean time without symptoms was 31 weeks. There were 24 cases of stent obstruction: 15 were treated with high-pressure 5% N-acetyl-cysteine and saline flush, achieving resolution in two cases; in three cases, attempts to recanalise the obstruction with a guidewire failed. The occluded stents were rsemoved in 22 patients: seven remained asymptomatic, 15 had recurrence of epiphora, nine received a new stent after dacryocystography and six underwent dacryocystorhinostomy. CONCLUSIONS: Advantages of the procedure include the lack of anatomical alterations to the lacrimal ducts and a low short-term complication rate, whereas limitations include restricted duration of stent patency. The pathophysiological causes of stent obstruction should be clarified in order to relate them to stent morphology.

Self-reported skin sensitivity in a general adult population in France: data of the SU.VI.MAX cohort.

OBJECTIVE: This study aimed to examine the frequency of self-assessed facial skin sensitivity and its different patterns, and the relationship with gender and sun sensitivity in a general adult population. METHODS: A standardized 11-item questionnaire investigating reactions experienced during the past year was developed. The questions explored different patterns of skin sensitivity: pattern I (blushing related to vascular reactivity), pattern II (skin reactions to certain environmental conditions), pattern III (skin reactions after substance contact), and for women pattern IV ('breakout of spots' related to menstrual cycle). Additional items were addressed for women and men, including sun sensitivity. The questionnaire was administered to a large middle-aged population involved in the 'Supplément en Vitamines et Minéraux Antioxydants' (SU.VI.MAX) cohort. RESULTS: Sensitive facial skin was reported by 61% of the women (n = 5074) and 32% of the men (n = 3448), and the frequency decreased with age. The frequency of patterns I, II and III was greater for women (78, 72 and 58%, respectively) than for men (56, 48 and 28%) of comparable classes of age. The frequency of pattern IV was reported by 49% of premenopausal women, and skin reactions after shaving by 41% of the men. Sun sensitivity was found to be a major component of skin sensitivity. Factor analysis showed that individuals with fair phototype frequently evoked reactions associated with pattern I, and skin redness and burning sensations were related to certain environmental conditions (pattern II). CONCLUSION: Skin sensitivity is a common concern that declines with age and is relevant for men as well as for women.

[Phototype, vitamin D status and bone mineral density among women at risk of osteoporosis]. / Phototype, statut en vitamine D et densité minérale osseuse chez des femmes à risque d'ostéoporose.

PURPOSE: The aim of this study was to test the influence of phototype and vitamin D status feature on the bone mineral density (BMD) of the femoral neck in a group of middle-aged women considered at risk of osteoporosis (low levels of vitamin D [25(OH)D3<78 nmol/L] and hyperparathyroidism [parathormone level>36 pg/mL]). METHODS: This two-step study was conducted on 122 French women enrolled in the SUVIMAX (supplémentation en vitamines et minéraux antioxydants: antioxidant vitamin and mineral supplementation) cohort. The impact of various variables on BMD, including age, body mass index (BMI), vitamin D status, alcohol intake, sun exposure intensity and phototype was investigated using regression models. RESULTS: No statistical link was found between BMD and the variables documenting vitamin D status and parathormone levels, nor phototype. Nevertheless, fair phototypes tended to be associated with lower BMD values. However, BMD decreased with age and increased with BMI and physical activity level. CONCLUSIONS: Whatever their phototype, adult women concerned about precarious vitamin D status should undergo a vitamin D supplementation in combination with an adequate calcium intake all year long and a proper sun protection. Moreover, a physical activity maintenance should provide an additional benefit for prevention of osteoporosis.

Factors influencing blood concentration of retinol, alpha-tocopherol, vitamin C, and beta-carotene in the French participants of the SU.VI.MAX trial.

OBJECTIVES: The data was collected during the inclusion step of the SUpplémentation en VItamines et Minéraux AntioXydants (SU.VI.MAX) study. This article deals with the study's first stage before any supplementation. The collected data shows factors influencing blood vitamin concentrations and may reflect the vitamin status of volunteers. MATERIAL AND METHODS: A total of 12,741 volunteers were enrolled in the SU.VI.MAX study 7,713 women 35-60 years of age and 5,028 men 50-60 years of age. The serum concentrations of retinol, alpha-tocopherol, and beta-carotene were measured by HPLC, and vitamin C concentration was measured by spectrofluorimetry using a Technicon continuous flow analysis apparatus. The volunteers recorded their 24 h diet by means of a specific terminal that was connected to the main central computer of the SU.VI.MAX study. Volunteers recorded the food they consumed daily and estimated its quantity by comparing pictures of dishes. RESULTS: Retinol concentration was significantly higher in older volunteers, and was higher in male than in female volunteers. Smoking had no effect on serum retinol, but the latter was higher in the autumn than in the winter. Serum retinol concentrations were higher in the Southwest region and lower in the Ile-de-France and East-Centre regions. Serum alpha-tocopherol was slightly higher in older volunteers and also higher in male volunteers. Serum alpha-tocopherol was significantly lower in smokers, and former smokers showed intermediate levels. Like retinol, serum alpha-tocopherol was higher in the autumn, and higher in the Southwest as compared to the East-Centre Serum beta-carotene was slightly higher in younger volunteers, and concentrations were higher in female than in male volunteers. Tobacco smoking decreased serum beta-carotene, which was higher in the autumn, and higher in the East, West, and North regions. Serum vitamin C was higher in female volunteers, and was not age related. Serum vitamin C was lower in smokers, was season-dependant, but contrary to fat-soluble vitamins, concentrations were higher in the winter and spring. Serum vitamin C was higher in the Southeast and East-Centre, but lower in the North region. CONCLUSION: These results suggest that serum retinol concentrations depend on gender, age, seasons, and location of residence. Similarly, serum alpha-tocopherol concentrations were slightly influenced by age, but more by tobacco smoking, seasons, dietary intake, and location of residence. Serum concentrations of beta-carotene depend on gender, age, smoking status, dietary intake, and location of residence. Serum vitamin C concentrations depend on gender, age, smoking status, seasons, dietary intake, and location of residence. Contrary to beta-carotene, retinol concentrations were higher in male than in female volunteers. Such a reversed relation suggests a higher beta-carotene-retinol conversion in male volunteers.

Presynaptic effects of anandamide and WIN55,212-2 on glutamatergic nerve endings isolated from rat hippocampus.

We examined the effects of the endocannabinoide-anandamide (AEA), the synthetic cannabinoid, WIN55,212-2, and the active phorbol ester, 4-beta-phorbol 12-myristate 13-acetate (4-beta-PMA), on the release of [(3)H]d-Aspartate ([(3)H]d-ASP) from rat hippocampal synaptosomes. Release was evoked with three different stimuli: (1) KCl-induced membrane depolarization, which activates voltage-dependent Ca(2+) channels and causes limited neurotransmitter exocytosis, presumably from ready-releasable vesicles docked in the active zone; (2) exposure to the Ca(2+) ionophore-A23187, which causes more extensive transmitter release, presumably from intracellular reserve vesicles; and (3) K(+) channel blockade by 4-aminopyridine (4-AP), which generates repetitive depolarization that stimulates release from both ready-releasable and reserve vesicles. AEA produced concentration-dependent inhibition of [(3)H]d-ASP release stimulated with 15 mM KCl (E(max)=47.4+/-2.8; EC(50)=0.8 microM) but potentiated the release induced by 4-AP (1mM) (+22.0+/-1.3% at 1 microM) and by A23187 (1 microM) (+98.0+/-5.9% at 1 microM). AEA's enhancement of the [(3)H]d-ASP release induced by the Ca(2+) ionophore was mimicked by 4-beta-PMA, which is known to activate protein kinase C (PKC), and the increases produced by both compounds were completely reversed by synaptosome treatment with staurosporine (1 microM), a potent PKC blocker. In contrast, WIN55,212-2 inhibited the release of [(3)H]d-ASP evoked by KCl (E(max)=47.1+/-2.8; EC(50)=0.9 microM) and that produced by 4-AP (-26.0+/-1.5% at 1 microM) and had no significant effect of the release induced by Ca(2+) ionophore treatment. AEA thus appears to exert a dual effect on hippocampal glutamatergic nerve terminals. It inhibits release from ready-releasable vesicles and potentiates the release observed during high-frequency stimulation, which also involves the reserve vesicles. The latter effect is mediated by PKC. These findings reveal novel effects of AEA on glutamatergic nerve terminals and demonstrate that the effects of endogenous and synthetic cannabinoids are not always identical.

Workplace air-conditioning and health services attendance among French middle-aged women: a prospective cohort study.

OBJECTIVES: To assess the relationship between type of ventilation in the workplace, health services attendance, and sickness absence among middle-aged women. METHODS: In a national sample of 920 professionally active women aged 49-65 yr from the SU.VI.MAX cohort, recruited from the general population in France, health services attendance and sickness absence were assessed prospectively during 1999. RESULTS: Being exposed to heating, ventilation, and air-conditioning (HVAC) systems in the workplace proved to be a risk factor for attendance at global and several specialist medical services. The adjusted odds ratio for otorhinolaryngologist attendance was 2.33 (95% CI = 1.35-4.04) in the HVAC group compared with the natural ventilation group, and 1.70 (1.13-2.58) for sickness absence. Dermatologist and global medical services attendance rates may also be higher in this group (P = 0.06 in both cases). CONCLUSIONS: Exposure to HVAC systems was a strong and significant risk factor for otorhinolaryngologist attendance and sickness absence. HVAC systems are prevalent in recent office buildings and have been shown to be associated with several adverse health effects in terms of morbidity and mortality. From a public-health perspective, our results outline the need for a quantitative assessment of the health impact of ventilation systems, taking into account the possible loss of production that exists in addition to the direct costs of medical services use.

Inhibition by anandamide and synthetic cannabimimetics of the release of [3H]D-aspartate and [3H]GABA from synaptosomes isolated from the rat hippocampus.

Cannabinoids (CB) can act as retrograde synaptic mediators of depolarization-induced suppression of inhibition or excitation in hippocampus. This mechanism may underlie the impairment of some cognitive processes produced by these compounds, including short-term memory formation in the hippocampus. In this study, we investigated several compounds known to interact with CB receptors, evaluating their effects on K(+)-evoked release of [3H]D-aspartate ([3H]D-ASP) and [3H]GABA from superfused synaptosomes isolated from the rat hippocampus. [3H]D-ASP and [3H]GABA release were inhibited to different degrees by the synthetic cannabinoids WIN 55,212-2; CP 55,940, and arachidonyl-2'-chloroethylamide/N-(2-chloroethyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (ACEA), as well as by the endocannabinoids, anandamide (AEA), and 2-arachidonoylglycerol (2-AG). Both types of release were also inhibited by capsaicin. The inhibition produced by each of the cannabinoid compounds and capsaicin was unaffected by capsazepine or by the CB1-receptor antagonists AM-251 and SR141716A. The mechanism underlying AEA- and synthetic CB-induced inhibition of the release of [3H]GABA and [3H]D-ASP from rat hippocampal synaptosomes might not involve activation of presynaptic CB1 receptors.

Indicators of abdominal adiposity in middle-aged participants of the SU.VI.MAX study: relationships with educational level, smoking status and physical inactivity.

OBJECTIVES: Abdominal fat accumulation is a risk factor for type 2 diabetes and cardiovascular disease. Identifying the demographic and lifestyle correlates of abdominal adiposity is an important step to target at-risk populations in prevention programs. There are few data of this kind in France. METHODS: Anthropometric indicators of overall (body mass index, BMI) and abdominal (waist hip ratio, WHR; waist circumference, WC) adiposity, educational level, smoking status, and physical activity were assessed in 6,705 middle-aged men and women participating in the SU.VI.MAX study. RESULTS: The likelihood of being obese was increased more than twice in physically inactive subjects of both genders after adjustment for age, smoking status and educational level (OR=2.22, CI95%: 1.74-2.83 in men; OR=2.38, CI95%: 1.84-3.09 in women). Having a high WHR (>=0.95 in men, >=0.80 in women) was more likely in subjects >=50 y, in current smokers, and less likely in men with higher education. The likelihood of having a high WHR was also increased in physically inactive subjects of both genders after adjustment for age, BMI, smoking status and educational level (OR=1.33, CI95%: 1.10-1.60 in men; OR=1.46, CI95%: 1.22-1.74 in women). Having a high WC (>=102 cm in men, >=88 cm in women) was positively associated with age and also with physical inactivity (OR=1.63, CI95%: 1.20-2.22 in women). CONCLUSIONS: These cross-sectional data suggest significant positive associations of physical inactivity with both the WHR and WC, independently of overall adiposity as assessed by the BMI.

Consequences of iron depletion on health in menstruating women.

OBJECTIVE: To examine the consequences of single iron depletion on health in menstruating women, a common but rarely investigated situation in industrialized countries. DESIGN: We studied data issued from the SU.VI.MAX. cohort via a transversal and a longitudinal (2-y follow-up) approach. SUBJECTS AND METHODS: Iron-depleted menstruating women (ferritin &<15 micro g/l, n=472) were compared with iron-sufficient (ferritin 30-80 micro g/l, n=393) menstruating women (aged 35-51 y) in terms of health variables and quality of life (DUKE score) using logistic regression and analysis of variance. RESULTS: The risk of any infection or of specific types of infections was not increased by iron deficiency. Regarding the DUKE health profile, no specific score was significantly different between the two groups: only the scores reflecting 'physical health' (P=0.09) and 'perceived health' (P=0.12) showed a trend toward a lower level, while the best score for 'mental health' (P=0.11) was found in the group of iron-depleted women. The only significant difference between iron-depleted and iron-sufficient women concerned memory disorders, which were significantly less common in iron-depleted women, Odds ratio=0.7 (0.6-0.9; P=0.03). CONCLUSION: There is no conclusive evidence that an absence of iron stores has negative consequences; however, we must consider that in the case of a worsening of the iron balance, it may lead to a rapid decrease in the level of functional compounds. SPONSORSHIP: The laboratory Robapharm, Pierre Fabre, France.

[The bank of biological material in the SU.VI.MAX study]. / La biothèque dans l'étude SU.VI.MAX.

The "SUpplémentation en VItamines et Minéraux AntioXydants" (SU.VI.MAX) study is a randomized double-blind, placebo-controlled, primary-prevention trial designed to test the efficacy of a daily supplementation with antioxidant vitamins and minerals at nutritional doses, in reducing several major health problems in industrialized countries, and especially the main causes of premature death (cancers and cardiovascular diseases). This 8-year cohort study started in 1994 in France; 13,535 eligible subjects (women aged 35 to 60, and men aged 45 to 60) were included in 1994 and will be followed up for 8 years. In this paper are described conditions and practical aspects for the realisation of the biological bank developped on the first sample (1994) and completed in 1996 and 1999. Biological material (buffy coat and plasma samples) are saved and stored at -196 degrees C, -80 degrees C and -20 degrees C for any further tests planned at later date (case-control studies and/or validation of new hypothesis).

Contribution of mineral waters to dietary calcium and magnesium intake in a French adult population.

OBJECTIVE: To assess the contribution of mineral water containing different amounts of calcium and magnesium to the total dietary intakes of these minerals DESIGN: Matched case control study using data issued from the Supplementation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) cohort. SUBJECTS: Subjects were water consumers-240 men and 424 women-divided into the following 4 groups (n=166 per group): regular drinkers of a calcium-rich and magnesium-rich mineral water (calcium, 486 mg/L; magnesium, 84 mg/ L), drinkers of a water classified as a moderately mineralized content (calcium, 202 mg/L; magnesium, 36 mg/L), drinkers of 2 low-mineralized waters (calcium, 9.9 to 67.6 mg/L and magnesium, 1.6 to 2 mg/L, respectively), and drinkers of tap waters. STATISTICAL ANALYSES: Quantitative data were compared using student's t test. Mean comparisons were performed in multivariate analysis by analysis of variance. RESULTS: Dietary calcium intake provided by the various food groups did not differ between the 4 consumer groups, except for calcium provided by mineral water. According to its calcium concentration, mineral water may contribute to one fourth of the total daily calcium intake. Subjects who regularly drink mineral-rich water have a calcium intake that is significantly higher (P< 10(-3)) than those drinking either low-mineral-content water or tap water. Dietary magnesium intake provided by the various food groups did not differ between the 4 consumer groups, except for magnesium provided by mineral water. Depending on the magnesium concentration of the mineral water, it contributed 6% to 17% of total daily magnesium intake. Drinkers of magnesium-rich mineral water and water with a moderate mineral content had magnesium intakes significantly (P< 10(-3)) higher than those of drinkers on low-mineralized or tap water. APPLICATIONS: Mineral-rich water may provide an important supplementary contribution to total calcium and magnesium intake. For dietetics professionals, it may provide-in place of the usual recommendations concerning the consumption of dairy products-a good way to improve calcium and magnesium intakes, particularly in subjects who don't like dairy products.

Relationships between changes in weight and changes in cardiovascular risk factors in middle-aged French subjects: effect of dieting.

OBJECTIVE: To investigate relationships between changes in weight and changes in cardiovascular risk factors in adults, taking intentionality of weight loss into account. DESIGN: Longitudinal study in middle-aged French subjects from the SU.VI.MAX cohort. SUBJECTS: A total of 1773 men (body mass index (BMI) 25.4+/-3.1 kg/m(2), mean+/-s.d) and 2316 women (BMI 23.3+/-3.8 kg/m(2)) aged 45 y and over at baseline. MEASUREMENTS: Weight, height, blood pressure, serum total cholesterol and fasting blood glucose were measured at baseline and after a 2 y follow-up. Self-reported dieting in order to lose weight, smoking status, leisure-time physical activity, health events and current treatments were assessed through questionnaires. RESULTS: In multivariate analyses, weight change was positively associated with changes in systolic and diastolic blood pressure (P=0.0002 in women, P=0.0001 in men) and with changes in serum total cholesterol (P=0.008 in women, P=0.02 in men), after adjustment for age, baseline level of each cardiovascular risk factor and current treatments. For example, in men, a weight loss of 5 kg was associated with a decrease of 2.5 mmHg in systolic blood pressure and of 1.5 mmHg in diastolic blood pressure. Taking into account self-reported dieting did not modify these associations. CONCLUSIONS: In both genders, systolic and diastolic blood pressure and serum cholesterol increased with weight gain and decreased with weight loss, independently of the intentionality to lose weight. At the population level, modest weight loss may have a substantial impact on cardiovascular risk, and preventing even modest weight gain in adults is an important goal in terms of public health.

Effect of two years' supplementation with natural antioxidants on vitamin and trace element status biomarkers: preliminary data of the SU.VI.MAX study.

The "SUpplementation en VItamines et Minéraux AntioXidants" (SU.VI.MAX) study is a randomized double-blind, placebo controlled, primary-prevention trial designed to test the efficacy of a daily supplementation with antioxidant vitamins (vitamin C, 120 mg; vitamin E, 30 mg; and beta-carotene, 6 mg) and minerals (selenium, 100 microg; and zinc, 20 mg) at nutritional doses (one to three times the daily recommended dietary allowances), in reducing the frequency of cancers and cardiovascular diseases. The study involves 12,735 eligible subjects (women aged 35-60 years, men aged 45-60 years) included in 1994 in France. They will be followed up for 8 years. The targeted population is the general population. The aim of this specific analysis is to assess the effect of 2 years of supplementation on biochemical indicators of vitamin and trace element on a subsample of 1000 subjects. The mean (+/- standard deviation) concentrations of plasma beta-carotene, alpha-tocopherol, vitamin C, selenium and zinc among participants who were randomly assigned to receive a daily supplementation with beta-carotene, vitamin E, vitamin C, selenium and zinc for 2 years were significantly higher than those who were assigned to receive placebo. Specifically, the mean concentrations among men in the intervention group were 0.86 +/- 0.70 micromol/L for beta-carotene, 35.3 +/- 9.3 micromol/L for alpha-tocopherol, 11.5 +/- 4.7 microg/ mL for vitamin C, 1.65 +/- 0.33 micromol/L for selenium, and 16.2 +/- 3.9 micromol/L for zinc. The mean concentrations among women in the intervention were 1.25 +/- 0.90 micromol/L for beta-carotene, 34.9 +/- 8.4 micromol/L for alpha-tocopherol, 12.6 +/- 4.0 microg/mL for vitamin C, 1.68 +/- 0.37 micromol/L for selenium, and 15.3 +/- 3.9 micromol/L for zinc. The values observed for beta-carotene and vitamin E in the supplementation group after 2 years of intervention are those that have been associated with the lowest risk of cancer in observational studies. They are definitely lower than concentrations reported in intervention studies showing an apparent negative effect of high levels of beta-carotene supplementation on the lung cancer incidence rate in high-risk subjects (initial level multiplied by 12-18). Data from the follow-up will ascertain if any plausible reduction in the incidence rate of cancers may be associated with such amounts of antioxidant agents.

Iron deficiency in Europe.

In Europe, iron deficiency is considered to be one of the main nutritional deficiency disorders affecting large fractions of the population, particularly such physiological groups as children, menstruating women and pregnant women. Some factors such as type of contraception in women, blood donation or minor pathological blood loss (haemorrhoids, gynaecological bleeding...) considerably increase the difficulty of covering iron needs. Moreover, women, especially adolescents consuming low-energy diets, vegetarians and vegans are at high risk of iron deficiency. Although there is no evidence that an absence of iron stores has any adverse consequences, it does indicate that iron nutrition is borderline, since any further reduction in body iron is associated with a decrease in the level of functional compounds such as haemoglobin. The prevalence of iron-deficient anaemia has slightly decreased in infants and menstruating women. Some positive factors may have contributed to reducing the prevalence of iron-deficiency anaemia in some groups of population: the use of iron-fortified formulas and iron-fortified cereals; the use of oral contraceptives and increased enrichment of iron in several countries; and the use of iron supplements during pregnancy in some European countries. It is possible to prevent and control iron deficiency by counseling individuals and families about sound iron nutrition during infancy and beyond, and about iron supplementation during pregnancy, by screening persons on the basis of their risk for iron deficiency, and by treating and following up persons with presumptive iron deficiency. This may help to reduce manifestations of iron deficiency and thus improve public health. Evidence linking iron status with risk of cardiovascular disease or cancer is unconvincing and does not justify changes in food fortification or medical practice, particularly because the benefits of assuring adequate iron intake during growth and development are well established. But stronger evidence is needed before rejecting the hypothesis that greater iron stores increase the incidence of CVD or cancer. At present, currently available data do not support radical changes in dietary recommendations. They include all means for increasing the content of dietary factors enhancing iron absorption or reducing the content of factors inhibiting iron absorption. Increased knowledge and increased information about factors may be important tools in the prevention of iron deficiency in Europe.

HIV-1 Gp120 protein modulates corticotropin releasing factor synthesis and release via the stimulation of its mRNA from the rat hypothalamus in vitro: involvement of inducible nitric oxide synthase.

In the present study, we examined whether the human immunodeficiency virus type I (HIV-I) gp120 coat protein can modulate corticotropin releasing factor (CRF) secretion by using the incubation of rat hypothalamic explants as an in vitro model. Treatment of the hypothalamic fragments with recombinant gp120 resulted in a time- and concentration-dependent increase in CRF release. The maximal dose of 10 nM gp120 increased CRF release by 56.4% after 1 h, and 78.4% after 3 h, as compared with their respective controls. The intra-hypothalamic amount of CRF was also increased by 54.7% and 77.3% vs. controls after 1 and 3 h, respectively. Moreover, the action of gp120 was blocked by pretreatment with cycloheximide, suggesting that the viral protein modulates CRF secretion via an increase in its synthesis. We also investigated the effects of gp120 on CRF gene expression. RNase protection analyses of total RNA isolated from the explants indicated that 10 nM gp120 significantly increases CRF mRNA in a time-dependent manner. Furthermore, gp120 did not modify CRF mRNA stability, suggesting that the viral protein modulates CRF gene expression at the transcriptional level. Analysis of the mechanisms that mediate gp120-induced CRF synthesis was conducted. The incubation of the explants with recombinant interleukin-1 (IL-1) type I receptor antagonist (hrIL-1 ra) did not antagonize the actions of gp120 at 1 and 3 h, indicating that the effect of the latter is independent of IL-1 mediated mechanisms. The involvement of some second messenger pathways was also investigated. Specific inhibitors of cAMP-PKA, cyclo-oxygenase or heme oxygenase pathways failed to antagonize the gp120-induced increase in CRF production. By contrast, incubation with nonselective inhibitors of nitric oxide synthase (NOS), L-NAME and L-NNA, or aminoguanidine (AG), a selective inhibitor of inducible NOS (iNOS), blocked CRF release and, AG, its mRNA accumulation, stimulated by gp120, whereas selective inhibitors of endothelial and neuronal NOS had no effect. In addition, only L-NAME, L-NNA and AG were able to inhibit the gp120-stimulated production of nitrites. These results indicate that gp120 directly stimulates CRF gene expression and peptide synthesis from the rat hypothalamus in vitro via the activation of iNOS. Therefore, the actions of this viral protein on the HPA axis may, in part, reflect its ability to modulate CRF synthesis.