Tratamiento de las úlceras neuropáticas con descargas

Las úlceras neuropáticas es una de las complicaciones que con más frecuencia presenta el paciente diabético. El principal objetivo en el tratamiento de las úlceras neuropáticas es potenciar los mecanismos fisiológicos de cicatrización, para ello es necesario actuar sobre los factores que retrasan este proceso. Uno de los principales factores que actúan como desencadenante y agravante en la aparición de una úlcera neuropática es el aumento de la presión plantar, condicionada por una alteración en el apoyo ya sea por causa estructural o biomecánica, al mismo tiempo esta hiperpresión continuada actúa retrasando los mecanismos de cicatrización. El método que ha demostrado mayor efectividad es el tratamiento de las úlceras neuropáticas plantares es el tratamiento con descargas. Vamos a exponer en este trabajo las diferentes técnicas de descarga que se pueden utilizar para tratar una ulcera neuropática a nivel ambulatorio.

Reduction of Concrete Deterioration by Ettringite Using Crystal Growth Inhibition Techniques, TR-431, 2001

Many researchers have concluded that secondary or delayed ettringite is responsible for serious premature deterioration of concrete highways. In some poorly performing Iowa concretes, ettringite is the most common secondary mineral but its role in premature deterioration is uncertain since some researchers still maintain that secondary ettringite does not itself cause deterioration. The current research project was designed to determine experimentally if it is possible to reduce secondary ettringite formation in concrete by treating the concrete with commercial crystallization inhibitor chemicals. The hypothesis is such that if the amount of ettringite is reduced, there will also be a concomitant reduction of concrete expansion and cracking. If both ettringite formation and deterioration are simultaneously reduced, then the case for ettringite induced expansion/cracking is strengthened. The experiment used four commercial inhibitors - two phosphonates, a polyacrylic acid, and a phosphate ester. Concrete blocks were subjected to continuous immersion, wet/dry and freeze/thaw cycling in sodium sulfate solutions and in sulfate solutions containing an inhibitor. The two phosphonate inhibitors, Dequest 2060 and Dequest 2010, manufactured by Monsanto Co., were effective in reducing ettringite nucleation and growth in concrete. Two other inhibitors, Good-rite K752 and Wayhib S were somewhat effective, but less so than the two phosphonates. Rapid experiments with solution growth inhibition of ettringite without the presence of concrete phases were used to explore the mechanisms of inhibition of this mineral. Reduction of new ettringite formation in concrete blocks also reduced expansion and cracking of the blocks. This relationship clearly links concrete expansion with this mineral - a conclusion that some research workers have disputed despite theoretical arguments for such a relationship and despite numerous observations of ettringite mineralization in prematurely deteriorated concrete highways. Secondary ettringite nucleation and growth must cause concrete expansion because the only known effect of the inhibitor chemicals is to reduce crystal nucleation and growth, and the inhibitors cannot in any other way be responsible for the reduction in expansion. The mechanism of operation of the inhibitors on ettringite reduction is not entirely clear but the solution growth experiments show that they prevent crystallization of a soluble ettringite precursor gel. The present study shows that ettringite growth alone is not responsible for expansion cracking because the experiments showed that most expansion occurs under wet/dry cycling, less under freeze/thaw cycling, and least under continuous soaking conditions. It was concluded from the different amounts of damage that water absorption by newly-formed, minute ettringite crystals is responsible for part of the observed expansion under wet/dry conditions, and that reduction of freeze resistance by ettringite filling of air-entrainment voids is also important in freeze/thaw environments.

Diseño de un protocolo para el cambio de prolongador en Diálisis Peritoneal

El cambio de prolongador del equipo de Diálisis Peritoneal es una intervención competencia de la enfermería que debe ser cumplimentada siguiendo un protocolo que minimice el riesgo de contaminación y por tanto de la aparición de peritonitis. No existen recomendaciones claras y unánimes sobre cómo desinfectar las conexiones, ya que esto va a depender fundamentalmente de si el conector del catéter es de titanio o no y de cómo debe cebarse el nuevo prolongador. Objetivo: Conocer como se realiza el cambio de prolongador en las diferentes unidades nefrológicas del Estado con el fin de consensuar el procedimiento más adecuado. Material y método: Estudio descriptivo transversal realizado en febrero de 2008 a partir de un cuestionario estructurado y autocumplimentado de diseño propio del que garantizó su validez y fiabilidad. En la encuesta se recogió la experiencia de la persona encuestada en el campo de la DP, el sistema utilizado, y el cumplimiento de los ítems que se consideraron fundamentales para una buena praxis en el procedimiento del cambio de prolongador, basados en la literatura consultada y el las recomendaciones de los proveedores de los productos para DP. Resultados: Se obtuvieron 53 encuestas de enfermeras que manifestaron tener experiencia en DP entre 3 meses y 32 años. El grado de cumplimiento de las acciones necesarias para cambiar el prolongador (lavado de manos, preparación campo estéril, lavado del conector) fue entre un 95 y un 100%, mientras que los ítems desinfección de la conexión y drenaje de líquido peritoneal tras el cambio obtuvieron grados de cumplimentación entre un 28 y un 83%. Conclusiones: Nuestro estudio presenta limitaciones, ya que se trataba de hacer una prospección inicial sobre el tema, se debe profundizar en él y consensuar un protocolo válido de cambio de prolongador para cualquiera de los sistemas que ofrece la industria y definir muy claramente el proceso de desinfección del conector y la conveniencia o no de realizar un recambio peritoneal completo tras el cambio.

Enhanced polyhydroxyalkanoates accumulation by Halomonas spp. in artificial biofilms of alginate beads.

Microbial mats are complex but stable, multi-layered and multi-functional biofilms, which are the most frequent bacterial formations in nature. The functional strategies and physiological versatility of the bacterial populations growing in microbial mats allow bacteria to resist changing conditions within their environment. One of these strategies is the accumulation of carbon- and energy-rich polymers that permit the recovery of metabolic activities when favorable conditions are restored. In the present study, we systematically screened microbial mats for bacteria able to accumulate large amounts of the ester carbon polymers polyhydroxyalkanoates (PHA). Several of these strains were isolated from Ebro Delta microbial mats and their ability to accumulate PHA up to 40-60 % of their dry weight was confirmed. According to two identification approaches (16S rRNA and ropD genes), these strains were identified as Halomonas alkaliphila (MAT-7, -13, -16), H. neptunia (MAT-17), and H. venusta (MAT-28). To determine the mode of growth yielding maximum PHA accumulation, these three different species were cultured in an artificial biofilm in which the cells were immobilized on alginate beads. PHA accumulation by cells that had detached from the biofilm was compared with that of their planktonic counterparts. Experiments in different culture media showed that PHA accumulation, measured as the relative fluorescence intensity after 48 h of incubation at 30 °C, was higher in immobilized than in planktonic cells, with the exception of cells growing in 5 % NaCl, in which PHA accumulation was drastically lower in both. Therefore, for obtaining high PHA concentrations, the use of immobilized cells may be a good alternative to the PHA accumulation by bacteria growing in the classical, planktonic mode. From the ecological point of view, increased PHA accumulation in detached cells from biofilms would be a natural strategy to improve bacterial dispersion capacity and, consequently, to increase survival in stressed environments.

Oferta formativa en terapias alternativas y complementarias para la asistencia al parto

Las terapias complementarias y alternativas (TCA) son las intervenciones y prácticas que no forman parte del sistema sanitario convencional. En la obstetricia, su uso es cada día más frecuente. Para asesorar a las gestantes es necesario tener unos conocimientos adecuados al respecto. El objetivo de este estudio es conocer la oferta formativa de las matronas en TCA para la atención al parto mediante una revisión bibliográfica y la consulta de fuentes documentales. El actual programa de formación no las contempla y su aprendizaje depende de motivaciones personales. Existe poca información al respecto. Para recomendarlas y utilizarlas con eficacia y seguridad, es necesario dedicar más recursos a la investigación e incorporarlas en los planes convencionales de estudio.

Synthesis of triheptanoin and formulation as a solid diet for rodents

Triheptanoin-enriched diets have been successfully used in the experimental treatment of various metabolic disorders. Maximal therapeutic effect is achieved in the context of a ketogenic diet where triheptanoin oil provides 3040% of the daily caloric intake. However, pre-clinical studies using triheptanoin-rich diets are hindered by the difficulty of administering to laboratory animals as a solid foodstuff. In the present study, we successfully synthesized triheptanoin to the highest standards of purity from glycerol and heptanoic acid, using sulfonated charcoal as a catalyst. Triheptanoin oil was then formulated as a solid, stable and palatable preparation using a ketogenic base and a combination of four commercially available formulation agents: hydrophilic fumed silica, hydrophobic fumed silica, microcrystalline cellulose, and talc. Diet compliance and safety was tested on C57Bl/6 mice over a 15-week period, comparing overall status and body weight change. Practical applications: This work provides a complete description of (i) an efficient and cost-effective synthesis of triheptanoin and (ii) its formulation as a solid, stable, and palatable ketogenic diet (triheptanoin-rich; 39% of the caloric intake) for rodents. Triheptanoin-rich diets will be helpful on pre-clinical experiments testing the therapeutic efficacy of triheptanoin in different rodent models of human diseases. In addition, using the same solidification procedure, other oils could be incorporated into rodent ketogenic diet to study their dosage and long-term effects on mammal health and development. This approach could be extremely valuable as ketogenic diet is widely used clinically for epilepsy treatment.

An angiotensin II- and NF-kappaB-dependent mechanism increases connexin 43 in murine arteries targeted by renin-dependent hypertension.

AIMS: Connexins (Cxs) play a role in the contractility of the aorta wall. We investigated how connexins of the endothelial cells (ECs; Cx37, Cx40) and smooth muscle cells (SMCs; Cx43, Cx45) of the aorta change during renin-dependent and -independent hypertension. METHODS AND RESULTS: We subjected both wild-type (WT) mice and mice lacking Cx40 (Cx40(-/-)), to either a two-kidney, one-clip procedure or to N-nitro-l-arginine-methyl-ester treatment, which induce renin-dependent and -independent hypertension, respectively. All hypertensive mice featured a thickened aortic wall, increased levels of Cx37 and Cx45 in SMC, and of Cx40 in EC (except in Cx40(-/-) mice). Cx43 was up-regulated, with no effect on its S368 phosphorylation, only in the SMCs of renin-dependent models of hypertension. Blockade of the renin-angiotensin system of Cx40(-/-) mice normalized blood pressure and prevented both aortic thickening and Cx alterations. Ex vivo exposure of WT aortas, carotids, and mesenteric arteries to physiologically relevant levels of angiotensin II (AngII) increased the levels of Cx43, but not of other Cx. In the aortic SMC line of A7r5 cells, AngII activated kinase-dependent pathways and induced binding of the nuclear factor-kappa B (NF-kappaB) to the Cx43 gene promoter, increasing Cx43 expression. CONCLUSION: In both large and small arteries, hypertension differently regulates Cx expression in SMC and EC layers. Cx43 is selectively increased in renin-dependent hypertension via an AngII activation of the extracellular signal-regulated kinase and NF-kappaB pathways.

Oferta formativa en terapias alternativas y complementarias para la asistencia al parto

Las terapias complementarias y alternativas (TCA) son las intervenciones y prácticas que no forman parte del sistema sanitario convencional. En la obstetricia, su uso es cada día más frecuente. Para asesorar a las gestantes es necesario tener unos conocimientos adecuados al respecto. El objetivo de este estudio es conocer la oferta formativa de las matronas en TCA para la atención al parto mediante una revisión bibliográfica y la consulta de fuentes documentales. El actual programa de formación no las contempla y su aprendizaje depende de motivaciones personales. Existe poca información al respecto. Para recomendarlas y utilizarlas con eficacia y seguridad, es necesario dedicar más recursos a la investigación e incorporarlas en los planes convencionales de estudio.

Clinical pharmacokinetics of mycophenolic acid and its metabolites in solid organ transplant recipient

Mycophenolate mofetil (MMF), an ester prodrug of the immunosuppressant mycophenolic acid (MPA), is widely used for maintenance immunosuppressive therapy and prevention of renal allograft rejection in renal transplant recipients.MPA inhibits inosine monophosphate dehydrogenase (IMPDH), an enzyme involved in the “de novo” synthesis of purine nucleotides, thus suppressing both T-cell and B-cell proliferation. MPA shows a complex pharmacokinetics with considerable interand intra- patient by between- and within patient variabilities associated to MPA exposure. Several factors may contribute to it. The pharmacokinetic modeling according to the population pharmacokinetic approach with the non-linear mixed effects models has shown to be a powerful tool to describe the relationships between MMF doses and the MPA exposures and also to identify potential predictive patients’ demographic and clinical characteristics for dose tailoring during the post-transplant immunosuppresive treatment.

Role of JNK in neurodegenerative diseases

The c-Jun N-terminal kinases (JNK) are members of the MAPK family and can be activated by different stimuli such as cellular stress, heat shock and ultra-violet irradiation. JNKs have different physiological functions and they have been linked to apoptosis in different cell types. Therefore, the JNK signalling pathway is an important target to prevent cell death. In the present chapter, the role of JNKs in neurodegenerative diseases will be discussed, as well as the pharmacological compounds that inhibit this signalling pathway as therapeutic intervention to prevent neuronal death.

Valganciclovir in adult solid organ transplant recipients: pharmacokinetic and pharmacodynamic characteristics and clinical interpretation of plasma concentration measurements.

Valganciclovir and ganciclovir are widely used for the prevention of cytomegalovirus (CMV) infection in solid organ transplant recipients, with a major impact on patients' morbidity and mortality. Oral valganciclovir, the ester prodrug of ganciclovir, has been developed to enhance the oral bioavailability of ganciclovir. It crosses the gastrointestinal barrier through peptide transporters and is then hydrolysed into ganciclovir. This review aims to describe the current knowledge of the pharmacokinetic and pharmacodynamic characteristics of this agent, and to address the issue of therapeutic drug monitoring. Based on currently available literature, ganciclovir pharmacokinetics in adult solid organ transplant recipients receiving oral valganciclovir are characterized by bioavailability of 66 +/- 10% (mean +/- SD), a maximum plasma concentration of 3.1 +/- 0.8 mg/L after a dose of 450 mg and of 6.6 +/- 1.9 mg/L after a dose of 900 mg, a time to reach the maximum plasma concentration of 3.0 +/- 1.0 hours, area under the plasma concentration-time curve values of 29.1 +/- 5.3 mg.h/L and 51.9 +/- 18.3 mg.h/L (after 450 mg and 900 mg, respectively), apparent clearance of 12.4 +/- 3.8 L/h, an elimination half-life of 5.3 +/- 1.5 hours and an apparent terminal volume of distribution of 101 +/- 36 L. The apparent clearance is highly correlated with renal function, hence the dosage needs to be adjusted in proportion to the glomerular filtration rate. Unexplained interpatient variability is limited (18% in apparent clearance and 28% in the apparent central volume of distribution). There is no indication of erratic or limited absorption in given subgroups of patients; however, this may be of concern in patients with severe malabsorption. The in vitro pharmacodynamics of ganciclovir reveal a mean concentration producing 50% inhibition (IC(50)) among CMV clinical strains of 0.7 mg/L (range 0.2-1.9 mg/L). Systemic exposure of ganciclovir appears to be moderately correlated with clinical antiviral activity and haematotoxicity during CMV prophylaxis in high-risk transplant recipients. Low ganciclovir plasma concentrations have been associated with treatment failure and high concentrations with haematotoxicity and neurotoxicity, but no formal therapeutic or toxic ranges have been validated. The pharmacokinetic parameters of ganciclovir after valganciclovir administration (bioavailability, apparent clearance and volume of distribution) are fairly predictable in adult transplant patients, with little interpatient variability beyond the effect of renal function and bodyweight. Thus ganciclovir exposure can probably be controlled with sufficient accuracy by thorough valganciclovir dosage adjustment according to patient characteristics. In addition, the therapeutic margin of ganciclovir is loosely defined. The usefulness of systematic therapeutic drug monitoring in adult transplant patients therefore appears questionable; however, studies are still needed to extend knowledge to particular subgroups of patients or dosage regimens.

Clinical pharmacokinetics of mycophenolic acid and its metabolites in solid organ transplant recipient

Mycophenolate mofetil (MMF), an ester prodrug of the immunosuppressant mycophenolic acid (MPA), is widely used for maintenance immunosuppressive therapy and prevention of renal allograft rejection in renal transplant recipients.MPA inhibits inosine monophosphate dehydrogenase (IMPDH), an enzyme involved in the “de novo” synthesis of purine nucleotides, thus suppressing both T-cell and B-cell proliferation. MPA shows a complex pharmacokinetics with considerable interand intra- patient by between- and within patient variabilities associated to MPA exposure. Several factors may contribute to it. The pharmacokinetic modeling according to the population pharmacokinetic approach with the non-linear mixed effects models has shown to be a powerful tool to describe the relationships between MMF doses and the MPA exposures and also to identify potential predictive patients’ demographic and clinical characteristics for dose tailoring during the post-transplant immunosuppresive treatment.

Synthesis of triheptanoin and formulation as a solid diet for rodents

Triheptanoin-enriched diets have been successfully used in the experimental treatment of various metabolic disorders. Maximal therapeutic effect is achieved in the context of a ketogenic diet where triheptanoin oil provides 3040% of the daily caloric intake. However, pre-clinical studies using triheptanoin-rich diets are hindered by the difficulty of administering to laboratory animals as a solid foodstuff. In the present study, we successfully synthesized triheptanoin to the highest standards of purity from glycerol and heptanoic acid, using sulfonated charcoal as a catalyst. Triheptanoin oil was then formulated as a solid, stable and palatable preparation using a ketogenic base and a combination of four commercially available formulation agents: hydrophilic fumed silica, hydrophobic fumed silica, microcrystalline cellulose, and talc. Diet compliance and safety was tested on C57Bl/6 mice over a 15-week period, comparing overall status and body weight change. Practical applications: This work provides a complete description of (i) an efficient and cost-effective synthesis of triheptanoin and (ii) its formulation as a solid, stable, and palatable ketogenic diet (triheptanoin-rich; 39% of the caloric intake) for rodents. Triheptanoin-rich diets will be helpful on pre-clinical experiments testing the therapeutic efficacy of triheptanoin in different rodent models of human diseases. In addition, using the same solidification procedure, other oils could be incorporated into rodent ketogenic diet to study their dosage and long-term effects on mammal health and development. This approach could be extremely valuable as ketogenic diet is widely used clinically for epilepsy treatment.

Role of JNK in neurodegenerative diseases

The c-Jun N-terminal kinases (JNK) are members of the MAPK family and can be activated by different stimuli such as cellular stress, heat shock and ultra-violet irradiation. JNKs have different physiological functions and they have been linked to apoptosis in different cell types. Therefore, the JNK signalling pathway is an important target to prevent cell death. In the present chapter, the role of JNKs in neurodegenerative diseases will be discussed, as well as the pharmacological compounds that inhibit this signalling pathway as therapeutic intervention to prevent neuronal death.

Clinical pharmacokinetics of mycophenolic acid and its metabolites in solid organ transplant recipient

Mycophenolate mofetil (MMF), an ester prodrug of the immunosuppressant mycophenolic acid (MPA), is widely used for maintenance immunosuppressive therapy and prevention of renal allograft rejection in renal transplant recipients.MPA inhibits inosine monophosphate dehydrogenase (IMPDH), an enzyme involved in the “de novo” synthesis of purine nucleotides, thus suppressing both T-cell and B-cell proliferation. MPA shows a complex pharmacokinetics with considerable interand intra- patient by between- and within patient variabilities associated to MPA exposure. Several factors may contribute to it. The pharmacokinetic modeling according to the population pharmacokinetic approach with the non-linear mixed effects models has shown to be a powerful tool to describe the relationships between MMF doses and the MPA exposures and also to identify potential predictive patients’ demographic and clinical characteristics for dose tailoring during the post-transplant immunosuppresive treatment.