Bioavailability of Oniria®, a Melatonin Prolonged-Release Formulation, Versus Immediate-Release Melatonin in Healthy Volunteers.

BACKGROUND: Melatonin is an endogenous substance which plays a key role in sleep induction by reducing sleep onset latency; it has been approved by the European Food Safety Authority as a food supplement for exogenous administration. Oniria® is a food supplement formulated as 1.98 mg of prolonged-release melatonin tablets; it displays a dual dissolution profile in vitro. OBJECTIVES: The main objective of the present study was to evaluate the relative oral bioavailability of Oniria®, in comparison with immediate-release tablets (IRT) with a similar melatonin content as a reference. We also attempted to characterize the circadian rhythm of endogenous melatonin. METHODS: We performed an open-label, cross-over, randomized, phase I clinical study with two sequences and three periods involving 14 healthy volunteers. We characterized the endogenous melatonin circadian profile (period 1) and pharmacokinetics (PK) of both Oniria® and the reference melatonin (periods 2 and 3). RESULTS: Two phases were clearly differentiated in the PK profile of Oniria®. An initial one, from dosing up to 2 h, and a delayed one from 2 to 11 h post-administration. During the initial phase, both melatonin formulations were equivalent, with a Cmax value close to 4000 pg/mL. However, in the delayed phase, Oniria® showed significantly higher melatonin concentrations than the IRT (three times higher at 4-6 h post-administration). Moreover, Oniria® exhibited concentrations above the endogenous melatonin peak of 80 pg/mL for up to 2.5 h versus the reference formulation, potentially suggesting an effect of Oniria®, not only in the induction of sleep, but also in the maintenance. CONCLUSION: Oniria® could be a highly promising food supplement, not only for sleep induction but also for the maintenance of sleep.

Comparación de aspectos de seguridad radiológica en odontopediatras con profesionales de distintas especialidades odontológicas de Lima ­ Perú

Objetivo: En los últimos años se viene realizando una labor de control y certificación de calidad en los temas relacionados a la radiación ionizante para obtener diversos objetivos; entre ellos, optimizar tratamientos, promover la salud ocupacional, etc. La presente investigación analiza el cumplimiento -por parte de profesionales en odontología- del uso de un protocolo de seguridad radiológica, creado a partir de leyes peruanas y recomendaciones internacionales. Metodología: Se elaboró una escala denominada "Protocolo de Seguridad Radiológica", integrada por 15 afirmaciones, cada uno con tres posibles respuestas y un puntaje, cuya suma representa el índice de cumplimiento de las normas de protección radiológica. Las afirmaciones y el protocolo en su conjunto pasaron por un análisis estadístico, con la finalidad de establecer la validez de confiabilidad de los mismos. La población de estudio abarcó profesionales de odontología de las especialidades de Endodoncia, Periodoncia, Odontopediatría; Rehabilitación Oral, Estética y Ortodoncia, de la Universidad Científica del Sur de Lima-Perú. De ella se seleccionó una muestra no probabilística de tipo intencional, integrada por 108 personas (34 hombres y 74 mujeres). Resultados: Se halló que los endodoncistas (puntaje promedio en la escala: 15.89, que representa el 52.97% del puntaje total de la misma) y odontopediatras (promedio 16.68, que representa el 55.6% del puntaje total) son los profesionales de las especialidades que menos se rigen en el "Protocolo de Seguridad Radiológica". Conclusiones: Se determinó que las prácticas o comportamientos de los diversos especialistas odontólogos, relacionados al cumplimiento del uso del "Protocolo de Seguridad Radiológica", no garantizan calidad en relación al mismo.

Caries dental y microbiota. Revisión / Dental caries and microbiot. Review

Cuando ocurre un desequilibrio en el balance de minerales en contacto con la superficie del esmalte dental y el balance es negativo hacia una pérdida de minerales se produce una degradación de la superficie y subsuperficie, este desequilibrio afecta al diente en su forma, función, sensibilidad y estética, esta alteración va a cambiar el status del microbioma. Investigaciones recientes sobre ADN y ARN relacionados a la lesión de caries han demostrado un ecosistema extraordinariamente diverso donde el conteo del Streptococo Mutans es sólo una muy pequeña fracción de la comunidad bacteriana hallada. Por lo tanto la dirección de prevención y/ó terapias específicas de caries dental no sólo deben estar enfocadas en el Streptococo Mutans porque se sabe que no están presentes en la primera colonización o inicio de la caries dental y se deben buscar estrategias dirigidas a la modulación de las interacciones entre microorganismos para poder tener una adecuada estrategia de prevención tomando como pilar principal a los microorganismos que inician la enfermedad. (AU)

When an imbalance occurs in the balance of minerals in contact with the surface of the dental enamel and the balance is negative towards a loss of minerals, a degradation of the surface and subsurface occurs, this imbalance affects the tooth in its shape, function, sensitivity and aesthetics, this alteration will change the status of the microbiome. Recent research on DNA and RNA related to caries lesion has demonstrated an extraordinarily diverse ecosystem where the Streptococcus Mutans count is only a very small fraction of the bacterial community found. Therefore, the prevention direction and / or specific therapies of dental caries should not only be focused on the Streptococcus Mutansbecause it is known that they are not present in the first colonization or onset of dental caries and strategies aimed at modulation should be sought of the interactions between microorganisms to be able to have an adequate prevention strategy taking as main pillar the microorganisms that initiate the disease. (AU)

The TP53 Arg72Pro polymorphism and lung cancer risk in a population of Northern Spain.

SUMMARY: Polymorphisms in tumor suppressor genes might contribute to the individual susceptibility to develop different types of cancer. Alterations in genes involved in cell cycle regulation and apoptosis, as tumor suppressor gene TP53, can lead to malignant transformations increasing the risk of developing cancer. We have investigated effects of polymorphism Arg72Pro on lung cancer risk, focusing on smoking and histology. Our study is a hospital-based case-control study designed with 589 lung cancer patients mainly with squamous cell carcinoma (215), adenocarcinoma (156) and small cell carcinoma (90), and 582 control subjects, matched in ethnicity, age and gender. Genotypes were determined by PCR-RFLP and the results were analysed using multivariate unconditional logistic regression, adjusted for age, gender and smoking status. The analysis showed a statistically significant increase of lung cancer risk in Pro carriers (Arg/Pro and Pro/Pro) (adjusted OR=1.32; 95% CI=1.03-1.69), especially for ever smokers (adjusted OR=1.34; 95% CI=1.04-1.73), heavy smokers (adjusted OR=1.48; 95% CI=1.01-2.16) and smokers of exclusively black tobacco (adjusted OR=1.45; 95% CI=1.04-2.00). Moreover, Pro carriers present an increased risk of developing small cell lung cancer (adjusted OR=1.70; 95% CI=1.07-2.69) and cancer in stage IV for NSCLC (adjusted OR=1.56; 95% CI=1.07-2.27). Our results suggest that polymorphism Arg72Pro in tumor suppressor gene TP53 increases the risk of lung cancer. The effect is especially strong for small cell lung cancer (SCLC) and heavy smokers.

Polymorphisms in XPC, XPD, XRCC1, and XRCC3 DNA repair genes and lung cancer risk in a population of northern Spain.

BACKGROUND: Polymorphisms in DNA repair genes have been associated to repair DNA lesions, and might contribute to the individual susceptibility to develop different types of cancer. Nucleotide excision repair (NER), base excision repair (BER), and double-strand break repair (DSBR) are the main DNA repair pathways. We investigated the relationship between polymorphisms in two NER genes, XPC (poly (AT) insertion/deletion: PAT-/+) and XPD (Asp312Asn and Lys751Gln), the BER gene XRCC1 (Arg399Gln), and the DSBR gene XRCC3 (Thr241Met) and the risk of developing lung cancer. METHODS: A hospital-based case-control study was designed with 516 lung cancer patients and 533 control subjects, matched on ethnicity, age, and gender. Genotypes were determined by PCR-RFLP and the results were analysed using multivariate unconditional logistic regression, adjusting for age, gender and pack-years. RESULTS: Borderline association was found for XPC and XPD NER genes polymorphisms, while no association was observed for polymorphisms in BER and DSBR genes. XPC PAT+/+ genotype was associated with no statistically significant increased risk among ever smokers (OR = 1.40; 95%CI = 0.94-2.08), squamous cell carcinoma (OR = 1.44; 95%CI = 0.85-2.44), and adenocarcinoma (OR = 1.72; 95%CI = 0.97-3.04). XPD variant genotypes (312Asn/Asn and 751Gln/Gln) presented a not statistically significant risk of developing lung cancer (OR = 1.52; 95%CI = 0.91-2.51; OR = 1.38; 95%CI = 0.85-2.25, respectively), especially among ever smokers (OR = 1.58; 95%CI = 0.96-2.60), heavy smokers (OR = 2.07; 95%CI = 0.74-5.75), and adenocarcinoma (OR = 1.88; 95%CI = 0.97-3.63). On the other hand, individuals homozygous for the XRCC1 399Gln allele presented no risk of developing lung cancer (OR = 0.87; 95%CI = 0.57-1.31) except for individuals carriers of 399Gln/Gln genotype and without family history of cancer (OR = 0.57; 95%CI = 0.33-0.98) and no association was found between XRCC3 Thr241Met polymorphism and lung cancer risk (OR = 0.92; 95%CI = 0.56-1.50), except for the 241Met/Met genotype and squamous cell carcinoma risk (OR = 0.47; 95%CI = 0.23-1.00). CONCLUSION: In conclusion, we analysed the association between XPC, XPD, XRCC1, and XRCC3 polymorphisms and the individual susceptibility to develop lung cancer in the Spanish population, specifically with a highly tobacco exposed population. We attempt to contribute to the discovery of which biomarkers of DNA repair capacity are useful for screening this high-risk population for primary preventing and early detection of lung cancer.

Poly (AT) polymorphism in intron 11 of the XPC DNA repair gene enhances the risk of lung cancer.

Reduced DNA repair capacity due to inherited polymorphisms may increase the susceptibility to smoking-related cancers. In this report, we investigate the relationship between xeroderma pigmentosum complementary group C poly (AT) insertion/deletion polymorphism (XPC-PAT) of the XPC gene and lung cancer risk in a hospital-based case-control study of 359 newly diagnosed lung cancer patients and 375 control subjects matched on age, sex, and catchment area. The XPC genotype was determined by PCR-RFLP, and the results were analyzed using logistic regression, adjusting for relevant covariates. We found that the frequency of the PAT+/+ genotype was higher in the cases (20.6%) than in the controls (14.1%; P = 0.057) and that the PAT+/+ subjects were at significantly increased risk for lung cancer [adjusted odds ratio (OR), 1.60; 95% confidence interval (95% CI), 1.01-2.55]. Stratified analysis revealed that the risk was higher in former smokers (OR, 2.15; 95% CI, 1.07-4.31) and older people (OR, 2.76; 95% CI, 1.02-7.51), although this probably occurs due to 63.4% of cases older than 73 years being ex-smokers. When stratified by histologic type, the variant genotype was associated with statistically significant increased risk for squamous cell carcinoma (OR, 1.93; 95% CI, 1.06-3.51). In conclusion, our findings support the hypothesis that PAT and intron 11 C/A XPC polymorphisms are linked in the Spanish population and may contribute to the risk of developing lung cancer probably due to a higher frequency of deletion of exon 12 and reduced DNA repair capacity of the XPC protein.