José Antonio Vázquez

Morbidity and mortality in Cushing's disease: an epidemiological approach

OBJECTIVE Although Cushings disease is a well documented clinical entity, there is no epidemiological information about it. The present study tries to obtain this information.

Statins as Neuroprotectants: A Comparative In Vitro Study of Lipophilicity, Blood-Brain-Barrier Penetration, Lowering of Brain Cholesterol, and Decrease of Neuron Cell Death

There is growing evidence to support the hypothesis that statins may act as neuroprotectants in several neuropathological conditions, including Alzheimers disease. The mechanisms for neuroprotection are only partially understood, however, and pleiotropic phenomena could be involved. We have made a comparative study of 9 statins (lovastatin, mevastatin, pravastatin, simvastatin, cerivastatin, atorvastatin, fluvastatin, pitavastatin, and rosuvastatin), analyzing several parameters that could be related to neuroprotection, such as chemical structure, lipophilicity, potential blood-brain-barrier penetration (BBB), 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibition, cholesterol modulation in neurons, glia, and human hepatocyte cell lines, and protection against neurodegeneration caused by tau hyperphosphorylation induced by okadaic acid. Our results indicate that monacolin J derivatives (natural and semi-synthetic statins) are the best candidates for the prevention of neurodegenerative conditions due to their higher potential BBB penetration capacity, cholesterol lowering effect on neurons with a satisfactory safety profile, and in vitro protection against cell death caused by okadaic acid in culture. Among the nine statins studied, simvastatin presented the best characteristics for preventing neurodegenerative conditions.

Chondroitin sulfate, hyaluronic acid and chitin/chitosan production using marine waste sources: characteristics, applications and eco-friendly processes: a review.

In the last decade, an increasing number of glycosaminoglycans (GAGs), chitin and chitosan applications have been reported. Their commercial demands have been extended to different markets, such as cosmetics, medicine, biotechnology, food and textiles. Marine wastes from fisheries and aquaculture are susceptible sources for polymers but optimized processes for their recovery and production must be developed to satisfy such necessities. In the present work, we have reviewed different alternatives reported in the literature to produce and purify chondroitin sulfate (CS), hyaluronic acid (HA) and chitin/chitosan (CH/CHs) with the aim of proposing environmentally friendly processes by combination of various microbial, chemical, enzymatic and membranes strategies and technologies.

Mutations in GCK and HNF‐1α explain the majority of cases with clinical diagnosis of MODY in Spain

Objective  The aim of this study was to group patients with MODY (maturity‐onset diabetes of the young) according to the genetic alterations underlying the disease and to investigate their clinical characteristics.

Dose-response relationships: an overview, a generative model and its application to the verification of descriptive models

Abstract Taking as a starting point a set of simple quantitative hypotheses regarding the possible relationships between cell receptors and effector molecules, a statistical algorithm or generative model is developed that simulates different types of dose–response (DR) profiles and whose results are used in two ways, both subject to empirical verification. In the first of these, the suitability of several common descriptive models for the study of DR relationships is discussed, and changes are introduced that improve their suitability for this conceptual framework, generalise their application and lead to the systematisation of possible interactions between more than one effector, as well as between the effects of self-stimulating and self-depressor mechanisms. Secondly, the generative model suggests the existence of some unexpected profiles and their possible explanations. Both the profiles and the hypotheses appear to be supported by experimental evidence.

Estudio prospectivo a 10 años sobre la incidencia y factores de riesgo de diabetes mellitus tipo 2

Fundamento Conocer la incidencia de diabetes mellitus tipo 2 en nuestro medio y los posibles factores de riesgo implicados. Pacientes y metodo Estudio prospectivo a 10 anos realizado en Lejona (Vizcaya) en una poblacion de mas de 30 anos de edad (n = 584). Tras un estudio de prevalencia efectuado en 1985, se revaluo 10 anos mas tarde a la misma poblacion. Se recogieron datos sobre edad, sexo, indice de masa corporal, antecedentes familiares de diabetes, presion arterial sistolica y diastolica y glucemia en sangre capilar tras sobrecarga oral de glucosa que se valoro segun criterios de la Organizacion Mundial de la Salud. Resultados La incidencia anual acumulada de diabetes mellitus tipo 2 fue de 8 casos/1.000 personas. En modelos multivariados de regresion logistica, la tolerancia anormal a la glucosa resulto ser el predictor mas importante (OR = 4,17; intervalo confianza del 95%: 1,80-9,63). La edad y el sexo tambien resultaron predictores significativos (p < 0,05) y casi significativos los antecedentes familiares de diabetes mellitus tipo 2 (p = 0,057). No lo fue el indice de masa corporal, aunque su incremento fue mayor en los enfermos que progresaron a diabetes mellitus tipo 2 frente a los que no. Conclusiones La incidencia acumulada de diabetes mellitus tipo 2 en Lejona fue similar a la encontrada en otros paises europeos. La presencia de tolerancia anormal a la glucosa y cifras mas elevadas de glucemia favorecen la progresion a diabetes mellitus tipo 2. El incremento del indice de masa corporal parece desempenar un papel precipitante en la progresion a diabetes mellitus tipo 2.

Mouse bioassay for palytoxin. Specific symptoms and dose-response against dose–death time relationships

Nowadays, a variety of protocols are applied to quantitate palytoxin. However, there is not desirable agreement among them, the confidence intervals of the basic toxicological parameters are too wide and the formal descriptions lack the necessary generality to establish comparisons. Currently, the mouse bioassay is the most accepted one to categorize marine toxins and it must constitute the reference for other methods. In the present work, the mouse bioassay for palytoxin is deeply analyzed and carefully described showing the initial symptoms of injected mice which are presented here in the first time. These symptoms clearly differ from the more common marine toxins described up to now. Regarding to the toxicological aspects two considerations are taking into account: (i) the empiric models based in the dose-death time relationships cause serious ambiguities and (ii) the traditional moving average method contains in its regular use any inaccuracy elements. Herein is demonstrated that the logistic equation and the accumulative function of Weibulls distribution (with the modifications proposed) generate satisfactory toxicological descriptions in all the respects.

Optimisation of antioxidant extraction from Solanum tuberosum potato peel waste by surface response methodology.

This study reports the optimised conditions (temperature, ethanol concentration and processing-time) for antioxidant extraction from potato peel (Agria variety) waste. At short extraction times (34 min), optimal yields of phenolic (TP) and flavonoid (Fv) compounds were reached at 89.9°C and ethanol concentrations of 71.2% and 38.6%, respectively. The main phenolic compounds identified in the extracts were chlorogenic (Cl) and ferulic (Fer) acids. A significant positive correlation was found between antioxidant activity and TP, Fv, Fer and Cl responses. Potato peel extracts were able to stabilize soybean oil under accelerated oxidation conditions, minimising peroxide, totox and p-anisidine indices. The production of hexanal and 2-hexenal in soybean oil samples was maximal for extracts obtained at intermediate temperatures and ethanol concentrations. Our results demonstrate potato peel waste is a good source of antioxidants able to effectively limit oil oxidation, while contributing to the revalorisation of these agrifood by-products.

Mendelian transmission, transgene dosage and growth phenotype in transgenic tilapia (Oreochromis hornorum) showing ectopic expression of homologous growth hormone

Abstract Gene transfer has offered a new tool for the development of improved fish strains for aquaculture. However, characterization is required before these strains can be introduced into national aquaculture programs. Transgenic tilapia ( O. hornorum urolepis ) were produced by the microinjection into early embryos of a transgene containing the tilapia growth hormone (tiGH) cDNA under the regulatory sequences derived from the human cytomegolovirus (CMV). A male containing 1 copy/cell of the transgene was selected to establish a transgenic tilapia line. The transgene was transmitted to F 1 –F 4 generations in a Mendelian fashion. Previous studies showed ectopic, low level expression of tiGH in brain, heart, gonad, liver and muscle cells of transgenic tilapia. Biochemical analyses indicated lower levels of cholesterol, free alanine and aspartic acid in the muscle of transgenic animals. Four month old transgenic homozygous (F 2 +/+ ) and heterozygous (F 2 −/+ ) tilapia and non-transgenic siblings ( N TRANSGENICS =14; N CONTROLS =11; N F2 −/+ =8; N F2 +/+ =6) were studied for 3 months grown communally in the same pond. Transgenic (F 2 −/+ +F 2 +/+ ), F 2 −/+ , and F 2 +/+ progeny were larger than non-transgenic siblings at P =0.009, P =0.005 and P =0.07 (Student t -test), respectively, suggesting a transgene-dosage effect. These results indicate stable germ line transformation in this fast-growing transgenic tilapia line.

Hyaluronic acid production by Streptococcus zooepidemicus in marine by-products media from mussel processing wastewaters and tuna peptone viscera

BackgroundHyaluronic acid is one of the biopolymers most commonly used by the pharmaceutical industry. Thus, there is an increasing number of recent works that deal with the production of microbial hyaluronic acid. Different properties and characteristics of the fermentation process have been extensively optimised; however, new carbon and protein sources obtained from by-products or cheap substrates have not yet been studied.ResultsMussel processing wastewater (MPW) was used as a sugar source and tuna peptone (TP) from viscera residue as a protein substrate for the production of hyaluronic acid (HA), biomass and lactic acid (LA) by Streptococcus zooepidemicus in batch fermentation. Commercial medium formulated with glucose and tryptone was used as the control. The parametric estimations obtained from logistic equations and maintenance energy model utilized for modelling experimental data were compared in commercial and low-cost media. Complete residual media achieved high production (3.67, 2.46 and 30.83 g l-1 of biomass, HA and LA respectively) and a high molecular weight of HA (approximately 2500 kDa). A simple economic analysis highlighted the potential viability of this marine media for reducing the production costs by more than 50%.ConclusionsThe experimental data and mathematical descriptions reported in this article demonstrate the potential of media formulated with MPW and TP to be used as substrates for HA production by S. zooepidemicus. Furthermore, the proposed equations accurately simulated the experimental profiles and generated a set of interesting parameters that can be used to compare the different bacterial cultures. To the best of our knowledge, this is the first work in which a culture media formed by marine by-products has been successfully used for microbial HA production.