Memory impairment induced by brain iron overload is accompanied by reduced H3K9 acetylation and ameliorated by sodium butyrate.

Iron accumulation in the brain has been associated to the pathogenesis of neurodegenerative disorders. We have previously demonstrated that iron overload in the neonatal period results in severe and persistent memory deficits in adult rats. Alterations in histone acetylation have been associated with memory deficits in models of neurological disorders. Here we examine histone acetylation in the brain and the effects of the histone deacetylase inhibitor (HDACi) sodium butyrate (NaB) on memory in the neonatal iron overload model in rats. Rats received vehicle or 30.0-mg/kg Fe⁺² orally at postnatal days 12-14. When animals reached adulthood, they were given training in either novel object recognition or inhibitory avoidance. Histone acetylation in the dorsal hippocampus and the effects of NaB were examined in separate sets of rats. Iron overload led to a reduction in H3 lysine 9 acetylation in the hippocampus, without affecting the acetylation of other H3 and H4 lysine residues. A single systemic injection of NaB (1.2 g/kg) immediately after training ameliorated iron-induced memory impairments. The results suggest that a reduction in H3K9 acetylation might play a role in iron-induced memory impairment and support the view that HDACis can rescue memory dysfunction in models of brain disorders.

[Comparison of the antihypertensive efficacy of and tolerance to 2 imidazoline receptor agonists: moxonidine and rilmenidine in monotherapy]. / Comparaison de l'efficacité antihypertensive et de la tolérance de deux agonistes des récepteurs aux imidazolines, la moxonidine et la rilmenidine administrées en monothérapie.

Two hundreds mild to moderate hypertensive patients (mean age 54 +/- 10, 115 males, 85 females) were randomised in a multicentre, double blind, two parallel groups trial in order to compare the efficacy of moxonidine (0.2 mg od) and rilmenidine (1 mg od), two selective I1 receptor agonists. The dosage had to be shifted after a four-week treatment period (moxonidine 0.4 mg od or rilmenidine 2 mg bid) if DBP > 90 mmHg. More than half of the patients had to be shifted to a double dose. The blood pressure was normalised (DBP < or = 90 mmHg) for 47% of the moxonidine patient's and 50% of the rilmenidine patients. The DBP decrease reached 7.3 mmHg in the moxonidine group and 8.0 mmHg in the rilmenidine group (P = 0.28). The SBP decrease was the same in the two groups (7.6 mmHg). Both drugs were well tolerated. The great affinity of moxonidine and rilmenidine for the I1 receptors and the weak affinity for the alpha 2 receptors were probably responsible of the small number of adverse events which are generally linked to the centrally acting antihypertensive drugs (asthenia, somnolence, oedema). Because moxonidine and rilmenidine are often to be prescribed at double dose and are often associated with other antihypertensives, moxonidine whose dosage could be shifted without having to increase the number of daily intakes could enhance the patient's comfort and make the compliance easier.

Treating elder neglect: collaboration between a geriatrics assessment team and adult protective services.

Neglect is the most common type of elder maltreatment in the United States. Currently, the only formal intervention available is provided by each state's adult protective service agency (APS). Elder neglect involves a complicated relationship among an indvidual's medical problems, social situation, and ability to function in the environment. Geriatric assessment teams are facile at dealing with such complex cases while APS caseworkers are expert in their ability to identify and confirm neglect. Forming a geriatric team that includes APS caseworkers is a logical and innovative approach to the growing problem of elder neglect.

Altered antioxidant status and increased lipid peroxidation in children with cystic fibrosis.

Cystic fibrosis often combines an infectious pathology with a syndrome of malabsorption, both potentially capable of favoring the deleterious effects of reactive oxygen species. This study was a simultaneous evaluation of the main antioxidant systems dependent on micronutrients and of lipid peroxidation products in 27 children with cystic fibrosis and 17 healthy children. Plasma of cystic fibrosis patients showed very low concentrations of beta-carotene (0.30 +/- 0.2 vs 1.63 +/- 0.5 mumol/g cholesterol, P < 0.0001) and a lower activity of selenium-dependent glutathione peroxidase (263.6 +/- 42 vs 296.9 +/- 57 U/L, P = 0.028). In parallel, the higher plasma concentrations of organic hydroperoxides (171.5 +/- 54.4 vs 122.6 +/- 23.3 mumol/L, P = 0.001) and of thiobarbituric acid reactants (2.9 +/- 0.6 vs 2.4 +/- 0.3 mumol/L, P = 0.004) reflected oxidative stress in this pathology. In addition, in these patients the major substrates of lipoperoxidation were significantly lower, whether they be linoleic acid (2.26 +/- 0.8 vs 3.60 +/- 0.9 mmol/L, P < 0.0001) or arachidonic acid (0.55 +/- 0.2 vs 0.74 +/- 0.2 mmol/L, P = 0.006). These results suggested that nutritional deficiencies resulting from malabsorption could considerably amplify disorders related to toxicity of reactive oxygen species. These nutritional deficits could also be aggravated by the destruction of antioxidant compounds by the inflammatory process.

Effect of double-blind cross-over selenium supplementation on lipid peroxidation markers in cystic fibrosis patients.

Lipid peroxidation was assessed in 27 cystic fibrosis children during a double-blind selenium supplementation study (2.8 micrograms of sodium selenite per kg per day) with a placebo control and inversion of treatment periods. Simultaneously, 17 healthy children living in the same area were also investigated as control subjects. Before any treatment whatsoever and despite a selenium status close to those of control subjects, cystic fibrosis patients showed significant increase in plasma lipid peroxidation markers. Thiobarbituric acid reactants (TBARs) were normalized after the first treatment period of 5 months in both cystic fibrosis groups receiving either selenium supplementation or placebo. In this latter group, TBARs were reduced despite a significant decrease in plasma selenium concentrations as compared with the control group. Organic hydroperoxide concentrations were also simultaneously normalized in both cystic fibrosis groups at the end of the second treatment period. These results showed that improvement of lipid peroxidation markers was not related to the selenium supplementation. Nevertheless, oxidative stress sustained by cystic fibrosis children must be taken into account so that it does not aggravate the prognosis of the disease.

[Ureteral stenosis caused by pelvic actinomycosis]. / Sténose urétérale par actinomycose pelvienne.

The authors report a case of pelvic actinomycosis causing ureteral obstruction in a 30-year-old woman. An intra-uterine device being in place for 6 years is considered as the main cause. The treatment, which included a laparotomy for abscess drainage, an indwelling double pigtail ureteral stent and a 9 month antibiotherapy led to recovery after an initial relapse.

Effect of double-blind crossover selenium supplementation on biological indices of selenium status in cystic fibrosis patients.

Twenty-seven cystic fibrosis patients received selenium supplementation (2.8 micrograms of sodium selenite per kilogram of body weight per day) or a placebo. This 5-month trial was conducted as a double-blind, placebo-controlled study. After an interval of 2 months, treatments of the two groups were interchanged (crossed over) for another 5-month period. A group of healthy subjects, living in the same area, was investigated simultaneously. No selenium deficiency was found either in plasma or in erythrocytes before the supplementation. This result was inconsistent with a previous study performed in 1988 in our laboratory. This change in selenium status can be explained by progress in the nutritional nursing care of children and by the addition of selenium to the diet. During the study, selenium concentrations in plasma decreased when patients received placebo treatment and increased during selenium intake. In one of the two groups a similar variation was found for glutathione peroxidase activities in plasma and erythrocytes, whereas erythrocyte selenium was normal and did not change in any group. Nowadays, in the Grenoble area, the selenium status of cystic fibrosis patients is close to normal. Nevertheless, this study indicates a fragile equilibrium, given that selenium concentrations cn be lowered by placebo or mildly increased by supplementation.

Malondialdehyde kit evaluated for determining plasma and lipoprotein fractions that react with thiobarbituric acid.

The determination of thiobarbituric acid reactants (TBARs) is a widely used method for investigating overall lipid peroxidation. An assay kit that could be used with plasma and lipid fractions would facilitate standardization of the method. The results reported here indicate that the malondialdehyde (MDA) kit manufactured by Sobioda (Grenoble, France) complies with criteria of good analytical practices. The detection limit was 0.11 mumol of MDA per liter of plasma. The within-run (CV = 1.8-3.3%) and between-run (CV = 3.3-4.4%) precisions were acceptable. The analytical recovery of MDA after supplementing human plasma samples with tetraethoxypropane standards varied from 88% to 100%. The mean (SD) lipoperoxide concentration determined in 32 healthy adults, ages 20-40 years, was 2.51 (0.25) mumol/L. No significant sex-related difference was noted: 2.57 (0.28) in men vs 2.44 (0.20) mumol/L in women. Applying the method to lipid fractions showed that lipoprotein fractions contain relatively little MDA: 0.07 (0.03) mumol/L of plasma for very-low-density lipoproteins and 0.19 (0.10) mumol/L for low-density lipoproteins.

[Allergy to Thyrophagus putrescentiae and Lepidoglyphus destructor in a population of young asthmatic adults]. / L'allergie à Thyrophagus putrescentiae et à Lepidoglyphus destructordans une population d'adultes jeunes asthmatiques.

In the present work a study has been made of the prevalence of allergy to two storage mites, Tyrophagus putrescentiae and Lepidoglyphus destructor in a population of 105 young adults in the east of France. Combination of skin tests and specific IgE measurements shows that 43.10% of the subjects were sensitive to Tyrophagus and 44.95% to Lepidoglyphus. Interpretation of skin tests remains uncertain, particularly concerning the source of the allergen used and it is most often also necessary to measure the specific serum IgE. As in many studies, most sensitization was found amongst farmers. In contrast, no difference was seen between rural and city dwellers, subjects who were in contact with small animals and those in contact with food for livestock if they were not farmers, not between declared asthmatics who lived in a humid place and those who lived in an environment that was drier. Certainly these mites appeared in the present study to be much more ubiquitous than supposed previously and the fact that they seemed to be carriers of allergens and antigens that were different from those of Dermatophagoides raises the question as to whether the need for hyposensitization treatment for them has been under-estimated.

[Allergy to Tyrophagus putrescentiae and Lepidoglyphus destructor in a population of young adult asthmatics]. / L'allergie à Tyrophagus putrescentiae et à lEpidoglyphus destructor dans une population d'adultes jeunes asthmatiques.

The goal of this work was the study of the prevalence of allergy to two mites, Tyrophagus putrescentiae and Lepidoglyphus destructor in a population of 105 young asthmatic men from East of France. The association of skin tests and specific IgE shows that 43.10% are allergic to Tyrophagus and 44.95% to Lepidoglyphus destructor. The significance of skin tests is doubtful and depends on the laboratories which provide the allergens. Therefore, specific IgE has to be performed. As in other studies it has been observed that farmers are very often sensitized. But, nose difference has been noticed between people living in town or in country, between those having contacts with pets or not, feeding the cattle or not (except for the farmers). In the same way, no difference has been noticed between the asthmatics living in a wet country and/or wet house and those living in a dry area.

[The complementary reasonable explorations to consider about young hypertensive patient. (With regard to 389 selection bed-rests in view of national service) (author's transl)]. / Les explorations complémentaires raisonnables à envisager chez le jeune hypertendu. A propos de 389 dossiers de sélection pour le service national.

About a retrospective study turning on 600 bed-rests during 3 years, the writers study 433 confirmed high blood pressures including 389 without therapeutic among which 67 p. 100 labil or limit H.B.P. and 33 p. 100 permanent H.B.P. By light of current ideas and withdrawn informations from complementary explorations done, they try to define a reasonable attitude concerning twenty years old young hypertensive male patients in view of selection. This attitude can be extended to the general field of young H.B.P. people. They establish that a good number of systemically researched elements are without great interest; functional signs, which are more the neurotonia witness than the H.B.P. consequence, heart or renal repercussion, negligible in this age, the too shematic distinction between permanent, labil or limit H.B.P. On the other hand, some parameters deserve to be searched : family antecedents (greater than 60 p. 100), obesity (approximately 20 p. 100), ocular repercussion (approximately 15 p. 100), perturbation of lipidemia, above all hypertriglyceridemia, hyperuricemia and urinary sediment abnomalies. As for I.V.U., in spite of an exact study of vascular times, and second reading by the same observer, it never allowed to display any renovascular H.B.P. Other pathologic uronephrologic established images are all almost associated to urinary sediment anomalies or to proteinuria. More, a few frequent incidents among young people and the price of the exam bring to purpose. I.V.U. only when H.B.P. context is hard or going with urinary signs. Other more specific exams (V.M.A., catecholamines) will be asked according to the context.