Evidence of immune system melatonin production by two pineal melatonin deficient mice, C57BL/6 and Swiss strains

Abstract:  We evaluated two pineal melatonin deficient mice described in the literature, i.e., C57BL/6 and Swiss mice, as animal models for studying the immunomodulatory action of melatonin. Plasma melatonin levels in C57BL/6 and Swiss strains were detectable, but lower than levels in control C3H/HENHSD mice. Since these strains are suppose to be pineal melatonin deficient an extrapineal melatonin synthesis may contribute to plasma levels. Regarding cells and tissues from the immune system, all of them were found to synthesize melatonin although at low levels. N-acetyltransferase (AANAT) mRNA was also amplified in order to analyze the alternative splicing between exons 3–4 described for pineal C57BL/6 mice which generates an inclusion of a pseudoexon of 102 bp. For the pineal gland, both the wild type and the mutant isoforms were present in all mice strains although in different proportions. We observed a predominant wild type AANAT mature RNA in thymus, spleen and bone marrow cells. Peripheral blood mononuclear cells (PBMC) culture shown an evident AANAT amplification in all strains studied. Although the bands detected were less intense in melatonin deficient mice, the amplification almost reached the control cell intensity after stimulation with phytohemaglutinin (PHA). In summary, melatonin detection and AANAT mRNA expression in inbred and outbred mice clearly indicate that different cells and tissues from the immune system are able to synthesize melatonin. Thus, the pineal defect seems not to be generalized to all tissues, suggesting that other cells may compensate the low pineal melatonin production contributing to the measurable plasma melatonin level.     

Isothermal phase transformations of a dental porcelain.

OBJECTIVES: The purpose of this investigation was to determine if the change in the leucite weight fraction during an isothermal heat treatment could be estimated by observing the deformation of PFM strips in a high-heating-rate, computer-controlled bending beam viscometer (BBV). METHODS: Specimens of a commercial body porcelain were fired according to the manufacturer's instructions-50 disk specimens for quantitative X-ray diffraction (XRD) and 100 bimaterial strip specimens for BBV. The XRD specimens were annealed at temperatures between 650 and 1000 degrees C, and leucite weight fraction was measured using an alumina internal standard. The BBV specimens were annealed in the BBV using time-temperature schedules designed to elucidate the leucite crystallization behavior between 700 and 1000 degrees C. Timoshenko's equation for a bimaterial thermostat was used to estimate the change in the thermal expansion of the porcelain near room temperature. Changes in leucite weight fraction were determined from these thermal expansion changes. RESULTS: The means and SDs were compared to values obtained by quantitative XRD. Good agreement was obtained between values of leucite weight fraction derived from beam deformation and those determined by quantitative XRD (p> or =0.45). The anneal sequence showed that the increase in leucite weight fraction at 800 or 900 degrees C is reversible by an anneal at 1000 degrees C. SIGNIFICANCE: The BBV technique yields comparable results to quantitative XRD and provides the opportunity to efficiently monitor porcelain leucite changes nondestructively over multiple heat treatments. This technique could prove useful for testing firing schedules designed to stabilize the leucite content in dental porcelain.     

Concurrent cutaneous localization of Langerhans cell sarcoma and chronic lymphocytic leukemia/small lymphocytic lymphoma in a patient with a history of chronic lymphocytic leukemia/small lymphocytic lymphoma

The phenomenon of histiocytic/dendritic cell sarcomas arising through transformation of a pre-existed lymphoproliferative disease is called transdifferentiation. Langerhans cell sarcoma transdifferentiating from chronic lymphocytic leukemia/small lymphocytic lymphoma is extremely rare and all the reported cases were localized in lymph nodes. We present a case of concurrent cutaneous localization of Langerhans cell sarcoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, in which the chronic lymphocytic leukemia/small lymphocytic lymphoma preceded the development of the Langerhans cell sarcoma. A cutaneous lesion from a 63-year-old patient with a history of chronic lymphocytic leukemia/small lymphocytic lymphoma was biopsied. The histologic examination revealed a mixture of two cell populations infiltrating diffusely the dermis. The first was composed of small lymphoid cells with somewhat monotonous appearance and mild nuclear atypia positive for PAX5, CD79a, CD20, CD23, CD5, and LEF1. The second was composed of large cells with abundant cytoplasm and pleomorphic nuclei. These cells were positive for CD1a, CD207, and S100 protein and exhibited a high mitotic rate and a high MIB-1 immunostaining index. Therefore, two different entities, chronic lymphocytic leukemia/small lymphocytic lymphoma and Langerhans cell sarcoma, were detected in the same skin fragment. The patient died 3 years after initial diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma.     

General disease costing principles

The term “disease costing” applies to those economic appraisal methodologies that ascertain the cost borne by a community because of a disease. This approach has been used to calculate the social and economic costs, in terms of loss of productivity, caused by a disease that only in the most serious cases results in the death of an individual. The production losses, also defined as indirect costs, are not the only social costs caused by diseases. In addition we point also to the negative variations that are reflected onto two fundamental quantities: consumption of resources and state of health. In addition to production losses and consumption of resources, the third group is unquestionably the most important in the healthcare sector, since it deals directly with variations in the state of health. This group is denoted by the term “human costs”. In the headache field, we are far behind other pathologies, where there is a greater knowledge of the economic aspects of both the pathology-related costs and the likely benefits resulting from different therapeutical approaches. Notwithstanding the disease costing problems that are also reflected in the cost-benefit techniques, it is important for the economic analysis to gain ground since there is a growing need to keep account of the available resources and the results attainable in the healthcare policies, from the central to the peripheral levels, where the valuation tools prove even more expedient.     

The paraventricular nucleus of the hypothalamus is a neuroanatomical substrate for the inhibition of palatable food intake by neuropeptide S

Neuropeptide S (NPS) is a recently discovered neurotransmitter that binds to its cognate G-protein coupled receptor, NPSR. Previous studies have shown that central administration of this peptide induces anxiolytic-like effects, promotes arousal and inhibits feeding in the same dose range. In the present study, we sought to investigate further the unique physiopharmacological profile of the NPS system by characterizing its effects on palatable food consumption in rats and comparing it with the effect of the classical anxiolytic benzodiazepine midazolam. The results demonstrated that midazolam (5.0 or 10.0 mg/kg) increases palatable food consumption, while intracerebroventricular (ICV) administration of NPS markedly reduces it. The anorectic effect of NPS (0.1–1.0 nmol per rat, ICV) was prevented by ICV pretreatment with the NPSR antagonist [ d -Cys(tBU)⁵]NPS (20.0–60.0 nmol per rat). Pretreatment with the nonselective corticotrophin-releasing factor receptor (CRF) antagonist alpha-helical CRF 9–41 (6.25 and 12.5 nmol per rat) completely reversed the hypophagic action of CRF (0.4 nmol per rat, ICV) but did not prevent the anorectic effect of ICV NPS (1.0 nmol per rat). Brain site-specific microinjection experiments revealed that NPS markedly inhibits palatable food intake if administered into the paraventricular nucleus of the hypothalamus (PVN). A similar but smaller and shorter lasting reduction of feeding was observed following intra-lateral hypothalamus administration, whereas no effect was observed following injection into the central amygdala. The present study demonstrates that NPS evokes a potent inhibition of palatable food consumption and that the PVN is an important site of action for its effect.     

Una propuesta práctica para seleccionar tratamientos quimioterápicos en pacientes oncológicos avanzados según su coste-efectividad

Background. Higher possibilities of chemotherapy for advanced patients, made the selections of best studies necessary. A practical approach based on efficacy and cost-effectiveness is shown. Methods. Variables of efficacy, quality of life and type of study provide its classification. Differential costs between schemes, per months of survival and per one more patient alive one more year are used for the cost-effectiveness. Results. Five schemes broadly used in ovary, breast, lung, colon and brain tumours are evaluated. All of them produce a moderate improvement in outcomes and an increase in costs: per months of increment in median of survival require between 1,500 and 25,500 euros extra. Conclusion. This approach is useful for making decision process.     

Lactobacillus plantarum ITM21B fermentation product and chickpea flour enhance the nutritional profile of salt reduced bakery products

The study aimed at improving the nutritional profile of yeast leavened salt reduced sliced bread and puccia type bread fortified with a wheat-based Lactobacillus plantarum ITM21B fermentation product (Bio21B). The protein content of bread made under laboratory conditions was increased by using: (i) chickpea flour (CF) (15% wt/wt flour) and Bio21B or (ii) the Bio21B containing a fungal protease to favour the gluten hydrolysis. Products showed increased protein and total amino acid content and improved protein digestibility. Moreover, the formula significantly affected the protein pattern of breads which, according to the results of the microfluidic two-dimensional electrophoresis (μ2DE) protein pattern, were discriminated as observed by the PCA plot. The use of CF was validated at industrial pilot plant producing salt reduced sliced bread and puccia type bread. The resulting products showed improved nutritional profile and a sensory quality comparable to the company’s products containing salt.