Osteopontin gene SNPs (rs9138, rs11730582) mediate susceptibility to external root resorption in orthodontic patients.

OBJECTIVE: External apical root resorption (EARR) is a frequent iatrogenic effect of orthodontic treatment. Substantial variability in responses to postorthodontic EARR has been observed among patients even when similar treatment protocols were used. This observation suggests that environmental and/or genetic variations between individuals may confer susceptibility or resistance to developing EARR. The objective of this study is to determine whether variants in the osteopontin gene, an essential mediator in the odontoclast fusion and attachment process, are positively/negatively associated with postorthodontic EARR. MATERIALS AND METHODS: Genetic screening of eighty-seven orthodontic patients was performed for two polymorphisms in the osteopontin gene cluster (rs9138 and rs11730582). Subjects were divided into groups, according to the presence or absence of EARR (>2 mm). Genotype distributions and allelic frequencies were calculated using the chi-square test. Logistic regression analysis was used to assess the extent to which clinical-related parameters interfered with the EARR. Odds ratios (OR) and 95% confidence intervals were also calculated. RESULTS: Data from this study show that subjects heterozygous and homozygous for the most frequent allele of the osteopontin gene at position 89261521 [OR: 0.035 (P = 0.035*) (allele A)] and 89253600 [OR: 0.20 (P = 0.025*) (allele T)], respectively, are protected against postorthodontic EARR. Nevertheless, a highly significant association was found in the comparative analysis of homozygous subjects [2/2 (CC)] for the osteopontin gene (rs9138), resulting in an increased risk of suffering postorthodontic EARR[OR: 4.10; P = 0.045*; CI: 95%]. Subjects who were homozygous [2/2 (CC)] for the osteopontin gene (rs11730582) were more likely, and to a greater extent, to be affected with EARR [OR: 11.68; P < 0.039*; CI: 95%] compared with other genotypes. CONCLUSION: Variations in the osteopontin gene (rs9138 and rs11730582) are determinants of a genetic predisposition to suffer EARR secondary to orthodontic treatment.

Head and neck cancer. An aetiopathogenetic study of non-endemic lymphoepithelioma.

An aetiopathogenetic analysis of non-endemic nasopharyngeal carcinoma (NPC) in European and Southern American patient groups was performed. Specifically, the study sought to determine the proportion of Epstein-Barr Virus (EBV)-positive tumour cells in NPC patients in two very different populations (Europe and South America) in areas not associated with a high incidence of NPC. Clinical data (age, sex and onset of clinical disease) were also analyzed. A total of 50 NPC samples, 24 from a European hospital (EH) and 26 from two South American hospitals (SAH), were included. Nuclear staining for Epstein-Barr virus-encoded small RNA (EBER) was performed by in situ hybridization (ISH). Latent membrane protein 1 (LMP1) expression was measured by immunohistochemical (IHC) analysis. A higher incidence of NPC was observed in patients > 40 years of age in EH; in SAH, by contrast, the incidence was higher in patients aged ≤ 40 years. Cervical lymph node metastasis was detected in 31 patients (of whom 84.6% were from SAH). A total of 72% of samples were EBERpositive; the incidence of EBER positivity was greater in type 3 NPCs. EBV was detected in a large proportion of epithelial cells in samples from both EH and SAH (75% vs. 69.2%, respectively). An association was found between EBER detection in lymphocytes and patient origin (p = 0.0001). LMP1 expression was detected in 64% of patients. ISH for the detection of EBER is the most sensitive technique for demonstrating EBV in tumour tissue. The incidence of EBV was not significantly greater in either of the study populations, but was significantly higher in patients with type 3 NPC. Definitive histological diagnosis of NPC was reached earlier in EH than in SAH, where metastases were more frequently diagnosed, suggesting that the disease had reached a more advanced stage by the time treatment was started.

The use of gene therapy vs. corticotomy surgery in accelerating orthodontic tooth movement.

OBJECTIVE: Alveolar corticotomy surgery is an adjunctive therapy for reducing orthodontic treatment duration. The activation pathways of bone resorption involved in the tooth movement (TM) process are directly linked to the receptor activator of the nuclear factor-kB ligand (RANKL). Whether similar molecular pathways through RANKL, are shared by the acceleratory TM process (corticotomy-induced or not), sustained acceleration would therefore be expected with transgenic overexpression of this factor. We hypothesize that maintaining transgenic overexpression of RANKL will accelerate TM under force over time rather than at the beginning of therapy only; this contrasts with the corticotomy procedure. MATERIAL AND METHODS: We transfected the pcDNA3.1(+)-mRANKL transgene in vitro into NIH3T3 cells, then evaluated by PCR, Western blot and ex vivo resorption assay. Quantification of RANKL immunofluorescence, fluorescence-based tartrate-resistant acid phosphatase+ (TRAP+) osteoclast counts and histological analyses of the bone resorption area were performed and clinically correlated after a 32-day in vivo experiment comparing corticotomy and gene therapy. RESULTS: In vitro experiments resulted in increased level of RANKL protein (46%, p<0.05) and greater mineral resorption (39%, p<0.05) compared to the controls. In vivo results showed increased RANKL immunoexpression for both corticotomy (twofold) and transfection groups (threefold) after 10 days. After 32 days, a similar result was obtained for the transfected group but not for the surgery group. These data correlate with the clinical effect of decelerating TM in the surgery group. CONCLUSIONS: Selective gene therapy with RANKL has been experimentally tested as an alternative method to corticotomy surgery, showing higher effectiveness than surgical methods used for acceleratory purposes in orthodontics.

Aplicación clínica de la terapia génica al movimiento dentario ortodóncico. Comparativa frente a la corticotomía alveolar / No disponible

El movimiento dentario ortodóncico se sustenta en bases biomoleculares y genéticas específicas en cada paciente. Sin embargo, existen determinados nexos comunes que rigen la velocidad del movimiento dentario a través de la estructura ósea alveolar. La disminución en el tiempo de tratamiento ortodóncico constituye aún hoy un reto pendiente por los profesionales de la materia, dependiendo éste directamente de la biología ósea. En la efervescente actualidad son muchos los autores que proponen la corticotomía alveolar como una técnica de apoyo a la ortodoncia en búsqueda de una aceleración inducida del movimiento dentario ortodóncico. Sin embargo, tal aceleración radica en última instancia en las bases biológicas del conocido como fenómeno de aceleración regional (RAP) desencadenado en el entorno óseo. Por otro lado, las vías moleculares de activación osteoclásticas y por tanto de reabsorción ósea, están íntimamente relacionadas con el (..) (AU)

Coenzyme Q10 distribution in blood is altered in patients with fibromyalgia.

OBJECTIVE: Coenzyme Q10 (CoQ(10)) is an essential electron carrier in the mitochondrial respiratory chain and a strong antioxidant. Signs and symptoms associated with muscular alteration and mitochondrial dysfunction, including oxidative stress, have been observed in patients with fibromyalgia (FM). The aim was to study CoQ(10) levels in plasma and mononuclear cells, and oxidative stress in FM patients. METHODS: We studied CoQ(10) level by HPLC in plasma and peripheral mononuclear cells obtained from patients with FM and healthy control subjects. Oxidative stress markers were analyzed in both plasma and mononuclear cells from FM patients. RESULTS: Higher level of oxidative stress markers in plasma was observed respect to control subjects. CoQ(10) level in plasma samples from FM patients was doubled compared to healthy controls and in blood mononuclear cells isolated from 37 FM patients was found to be about 40% lower. Higher levels of ROS production was observed in mononuclear cells from FM patients compared to control, and a significant decrease was induced by the presence of CoQ(10). CONCLUSION: The distribution of CoQ(10) in blood components was altered in FM patients. Also, our results confirm the oxidative stress background of this disease probably due to a defect on the distribution and metabolism of CoQ(10) in cells and tissues. The protection caused in mononuclear cells by CoQ(10) would indicate the benefit of its supplementation in FM patients.

Cytotoxic effects of amitriptyline in human fibroblasts.

Amitriptyline is a tricyclic antidepressant widely used in the treatment of chronic pain. The objective of the present study was to investigate the potential cytotoxic effects of amitriptyline in human fibroblasts primary culture. Human fibroblast cells were cultured from healthy subjects and incubated with 50 microM and 100 microM amitriptyline. Cell counting was performed to study dose-dependency of toxicity. Lipid peroxidation analysis and western blotting for antioxidants catalase and mitochondrial superoxide dismutase (MnSOD) were carried out in order to evaluate oxidative stress. To investigate mitochondria damage the following determinations were made: cytochrome c, citrate synthase, and mitochondrial membrane potential (DeltaPsi(m)). Amitriptyline reduced significantly the number of cultured cells, resulting in a decrease of 45.2%, 65.0% and 94.9% when treated with 20 microM, 50 microM and 100 microM amitriptyline, respectively. This drug enhanced the production of oxidized products during lipid peroxidation, inverting the reduced/oxidized ratio to 25% reduction and 75% oxidation after 24h of amitriptyline administration. A decreased in catalase protein levels has been also observed. Moreover, amitriptyline treatment induced a significant decrease of cytochrome c, DeltaPsi(m), and citrate synthase activity; revealing mitochondrial damage. These findings suggest that amitriptyline has a strong cytotoxic effect in human fibroblasts, decreasing growth rate and mitochondrial activity, and increasing oxidative stress.

[Dietary and personal hygiene habits of adolescents in a rural population]. / Hábitos dietéticos y de higiene personal en adolescentes de una población rural.

BACKGROUND: A healthy diet and adequate personal hygiene are essential factors for good health. Adolescents gradually achieve a degree of autonomy in these areas. The aim of the study is to find out the diet and hygiene habits of adolescents in Navalcarnero, a rural town in the Autonomous Region of Madrid (Spain). METHODS: A descriptive study of a cross section of the relevant population, by previously validated, self-completed and anonymous questionnaire, filled in by adolescents (3 degrees BUP/ESO/FP) in by 13- and 14-year old school children (EGB.) The diet survey assessed the weekly consumption frequency of different foodstuffs. RESULTS: The respondents normally had milk and cocoa for breakfast, with toast or a bun. Lunch was more abundant than the evening meal, and more fruit was consumed more often in the former. Most of the children drank milk every day, usually in its natural state, but in two out of three cases, the consumption of dairy products was not as recommended, vegetable consumption was low. Among the children of BUP/ESO/FP, the girls consumed greens, salad, fruit and sliced bread more often, this difference being particularly marked in the case of the bread, and the boys consumed considerably more meat and bread of the French-stick kind. With respect to personal hygiene, most of them have a shower and wash their hair every two or three days and brush their teeth and change their underwear on a daily basis; the girls proved to be much more assiduous in having a shower, brushing their teeth and changing their underwear. CONCLUSIONS: In some areas, behaviour as regards diet and hygiene shows differences depending on the sex of the individual, certain habits ought to be improved upon.