A Mechanism-Based Sphingosine-1-phosphate Lyase Inhibitor.

The synthesis of a series of vinylated analogues of sphingosine-1-phosphate together with their unambiguous configurational assignment by VCD methods is reported. Among them, compound RBM10-8 can irreversibly inhibit human sphingosine-1-phosphate lyase (hS1PL) while behaving also as an enzyme substrate. These findings, together with the postulated mechanism for S1PL activity, reinforce the role of RBM10-8 as a new mechanism-based hS1PL inhibitor.

DFT-Aided Vibrational Circular Dichroism Spectroscopy Study of (-)-S-cotinine.

The implementation of a strategy comprising the use of vibrational circular dichroism spectroscopy and DFT calculations allows determination of the solution-state conformational distribution in (-)-S-cotinine, giving further proof of the extra conformer-discriminating potential of this experimental technique, which may offer unique molecular fingerprints of subtly dissimilar molecular conformers of chiral samples. Natural bond orbital electronic structure calculations of the rotational barrier height between the two main conformers of the species indicate that hyperconjugative effects are the key force governing the conformational equilibrium. The negligible effect of the solvent's polarity over both structure and conformational energy profile supports this result.

Extracellular to Intracellular Water Ratio Determined by Bioimpedance is Associated with Mortality in Patients Admitted for Diabetic Foot Ulcers.

An increased extracellular water/intracellular water (ECW/ICW) ratio determined by bioimpedance has been related to mortality in patients undergoing hemodialysis. We aimed to evaluate the impact of body water distribution in patients with diabetes-related foot ulcers. Seventy-six patients were evaluated with bioimpedance, handgrip strength, and laboratory examinations. The ECW/ICW ratio is a prognostic factor for early mortality.

Fourier Transform Infrared Spectroscopy and Vibrational Circular Dichroism Assisted Elucidation of the Solution-State Supramolecular Speciation in Racemic and Enantiopure Ketoprofen.

The molecular structure and solution-state molecular interactions in the popular non-steroidal anti-inflammatory drug, ketoprofen, are extensively studied with the aim of gaining a better understanding of the chemical behavior of its solution state and its connection to its nucleation pathway and crystallization outcome. Using as reference solid-state X-ray structures of enantiomeric and racemic forms of ketoprofen, a set of self-assembly models underpinned by density functional theory calculations has been considered for the analysis of spectroscopic data, infrared (IR) and vibrational circular dichroism (VCD), obtained for solutions of the samples as a function of composition and solvent. From our results it can be concluded that, contrary to the general belief for generic carboxylic acids, there are no cyclic dimeric structures of ketoprofen present in solution, but rather linear arrays made up of two (in high polar or diluted media) or more units (in low polar or low dilution media). This observation is in line with the idea that the weak contacts (other than H-bonding) would hold the key to molecular self-assembly, in agreement with recent studies on other aromatic carboxylic acids.

Phosphate disorders and clinical management of hypophosphatemia and hyperphosphatemia. / Trastornos del fosfato y actitud clínica ante situaciones de hipofosfatemia e hiperfosfatemia.

Serum phosphorus levels range from 2.5 and 4.5mg/dL (0.81-1.45 mmol/L) in adults, with higher levels in childhood, adolescence, and pregnancy. Intracellular phosphate is involved in intermediary metabolism and other essential cell functions, while extracellular phosphate is essential for bone matrix mineralization. Plasma phosphorus levels are maintained within a narrow range by regulation of intestinal absorption, redistribution, and renal tubular absorption of the mineral. Hypophosphatemia and hyperphosphatemia are common clinical situations, although changes are most often mild and oligosymptomatic. However, acute and severe conditions that require specific treatment may occur. In this document, members of the Mineral and Bone Metabolism Working Group of the Spanish Society of Endocrinology and Nutrition review phosphate disorders and provide algorithms for adequate clinical management of hypophosphatemia and hyperphosphatemia.

[Late onset hypopituitarism due to hypoplasia of the adenohypophysis with invisible stalk and ectopic neurohypophysis in a 67-year-old patient]. / Inicio tardío de hipopituitarismo debido a hipoplasia adenohipofisaria y ausencia de tallo con neurohipófisis ectópica en un paciente de 67 años de edad.

Congenital hypopituitarism due to pituitary stalk and anterior pituitary hypoplasia accompanied by an ectopic posterior pituitary lobe is a rare disorder causing multiple hormone deficiencies. Clinical signs can be present at birth (hypoglycemia, prolonged jaundice and micropenis) and there can be severe growth restriction. Therefore, diagnosis is usually performed in childhood. We present the uncommon case of a 67-year-old man with hypopituitarism due to hypoplasia of the anterior pituitary and pituitary stalk together with an ectopic posterior pituitary who presented symptoms of hyponatremia due to adrenocorticotropic hormone deficiency.

Synthesis and Structural Characterization of a Ubiquitous Transformation Product (BTS 40348) of Fungicide Prochloraz.

Prochloraz is a widely used imidazole fungicide that has to be analyzed together with its metabolites or transformation products for food safety monitoring purposes in the European Union. Although the focus in food of plant origin has been set on metabolites BTS 44595 and BTS 44596, we consider relevant the study of BTS 40348 metabolite, too, because it has been detected in both raw and processed foods based on citrus fruits in the EU. Metabolite BTS 40348 should be monitored in surface water due to its ecotoxicological effects. In this work, the synthesis and structural characterization of BTS 40348 metabolite of fungicide prochloraz is presented, because the structure is closely related to the chemistry and biological activity of the substance. Characterization using 13C and 1H NMR, infrared (IR), and Raman spectroscopy is detailed, together with confirmation by electrospray mass spectrometry analysis.

[Consensus document about the nutritional evaluation and management of eating disorders: anorexia nervosa, bulimia nervosa, binge eating disorder, and others]. / Resumen ejecutivo "Consenso sobre la evaluación y el tratamiento nutricional de los trastornos de la conducta alimentaria: anorexia nerviosa, bulimia nerviosa, trastorno por atracón y otros".

Eating disorders (ED) are characterized by persistent changes in eating habits that negatively affect a person's health and psychosocial abilities. They are considered psychiatric disorders, highly variable in their presentation and severity, with a huge impact on nutrition, which conditions various therapeutic approaches within a key multidisciplinary context. A group of experts in nutrition, we decided to set up a task force adscribed to the "Sociedad Española de Nutrición Parenteral y Enteral" (SENPE), which has stated as one of its goals the development of a consensus document to generate a protocol based on the best scientific evidence and professional experience available in order to improve health care in this field.

[Consensus document about the nutritional evaluation and management of eating disorders: anorexia nervosa]. / Consenso sobre la evaluación y el tratamiento nutricional de los trastornos de la conducta alimentaria: anorexia nerviosa.

Anorexia nervosa is the most common psychiatric disease among young women and it is assumed to be of multifactorial origin. Diagnostic criteria have recently been modified; therefore amenorrhea has ceased to be a part of them. This disease shows a large variability in its presentation and severity which conditions different therapeutic approaches and the need to individualize the treatment, thus it is indispensable a multidisciplinary approach. The goals are to restore nutritional status (through an individualized diet plan based on a healthy consumption pattern), treat complications and comorbidities, nutritional education (based on healthy eating and nutritional patterns), correction of compensatory behaviors and relapse prevention. The treatment will vary according to the patient's clinical situation, and it may be performed in outpatient clinics (when there is clinical stability), in a day hospital or ambulatory clinic (intermediate mode between traditional outpatient treatment and hospitalization) or hospitalization (when there is outpatient management failure or presence of serious medical or psychiatric complications). Artificial nutrition using oral nutritional supplements, enteral nutrition and exceptionally parenteral nutrition may be necessary in certain clinical settings. In severely malnourished patients the refeeding syndrome should be avoided. Anorexia nervosa is associated with numerous medical complications which determines health status, life quality, and is closely related to mortality. There is little clinical evidence to assess the results of different treatments in anorexia nervosa, when most of the recommendations are being based on expert consensus.

[Consensus document about the nutritional evaluation and management of eating disorders: bulimia nervosa, binge eating disorder, and others]. / Consenso sobre la evaluación y el tratamiento nutricional de los trastornos de la conducta alimentaria: bulimia nerviosa, trastorno por atracón y otros.

Bulimia nervosa and binge eating disorder are unique nosological entities. Both show a large variability related to its presentation and severity which involves different therapeutic approaches and the need to individualize the treatment, thus it is indispensable a multidisciplinary approach. Patients with bulimia nervosa may suffer from malnutrition and deficiency states or even excess weight, while in binge eating disorders, it is common overweight or obesity, which determine other comorbidities. Many of the symptoms and complications are associated with compensatory behaviors. There are many therapeutic tools available for the treatment of these patients. The nutritional approach contemplates the individualized dietary advice which guarantees an adequate nutritional state and nutritional education. Its objective is to facilitate the voluntary adoption of eating behaviors that promote health and allow the long-term modification of eating habits and the cessation of purgatory and bingeing behaviors. Psychological support is a first-line treatment and it must address the frequent disorder of eating behavior and psychiatric comorbidities. Psychotropic drugs are effective and widely used although these drugs are not essential. The management is carried out mainly at an outpatient level, being the day hospital useful in selected patients. Hospitalization should be reserved to correct serious somatic or psychiatric complications or as a measure to contain non-treatable conflict situations. Most of the guidelines' recommendations are based on expert consensus, with little evidence which evaluates clinical results and cost-effectiveness.

Solvent Effects on the Monomer/Hydrogen-Bonded Dimer Equilibrium in Carboxylic Acids: (+)-(S)-Ketopinic Acid as a Case Study.

The hydrogen-bond-assisted self-association process of a chiral semirigid carboxylic acid, namely, (+)-(S)-ketopinic acid, has been studied. The multiconformational monomer/dimer equilibrium has been evaluated by means of a concentration-dependent FTIR study that enabled the experimental equilibrium constants of the dimer formation reaction (Kdim ) to be determined in two solvents of different polarity. In CDCl3 , dimeric forms predominate, even in diluted solutions (KdimCF =5.074), whereas in CD3 CN the self-association process is hindered and monomers are always the main species, irrespective of solute concentration (KdimAN =0.194). The reliability of the dimerization constants and the derived mono- and dimeric experimental fractions have been proven by means of accurate matching between the experimental vibrational circular dichroism spectra of the species and the theoretical spectra generated by considering the simultaneous weighted contributions of the concomitant monomers and dimers.

DFT study of the hydrolysis reaction in atranes and ocanes: the influence of transannular bonding.

Thermochemical kinetics of hydrolysis reactions of compounds with transannular intramolecular M…N bonds, i.e., atranes RM(OCH2CH2)3N and ocanes R2M(OCH2CH2)2NH (M = Si, Ge; R = F, Cl, Me), is studied at the B3LYP/aug-cc-pVDZ theoretical level. Several DFT methods are assessed for the reproduction of the experimental activation barrier for the Si-O bond cleavage of 1-methylsilatrane. Activation barriers for atranes and ocanes show the tendency for their growth with the decrease of the electronegativity of a substituent R on going from F to Me and their decrease from Si to Ge. Hydrolysis activation barriers of atranes and ocanes are compared with those of their acyclic analogs RM(OCH3)3 and R2M(OCH2)2NH in order to study the role of transannular M…N bonds in the stability of these molecules to hydrolysis. Substantially larger barriers for atranes support the opinion that stability of atranes may be explained by the formation of intramolecular bonds; however, the strengthening of transannular M…N bonds results in lower M-O cleavage barriers. It was proposed that the M-O cleavage barrier height is determined not by a weak M…N bonding itself, but rather by the contribution of a nitrogen lone pair to the antibonding orbitals of M-O bonds. The NBO analysis show that this interaction increases with the decrease of the electronegativity of a substituent R and decreases on going from atranes to ocanes. In ocanes, the presence of M…N bonds does not kinetically hinder the hydrolytic process; M-O cleavage activation barriers for acyclic analogs are higher. M-Hal cleavage barriers are substantially higher than those for M-O cleavage for R = F, but lower for R = Cl. Graphical Abstract The experimental barrier height of the Si-O bond cleavage in 1-methylsilatrane is well reproduced when three explicit water molecules are included in the B3LYP/aug-cc-pVDZ theoretical model.

Implementation of subcutaneous insulin protocol for non-critically ill hospitalized patients in andalusian tertiary care hospitals.

INTRODUCTION: In 2009, the Andalusian Society of Endocrinology and Nutrition designed a protocol for subcutaneous insulin treatment in hospitalized non-critically ill patients (HIP). OBJECTIVE: To analyze implementation of HIP at tertiary care hospitals from the Andalusian Public Health System. METHOD: A descriptive, multicenter study conducted in 8 tertiary care hospitals on a random sample of non-critically ill patients with diabetes/hyperglycemia (n=306) hospitalized for ≥48 hours in 5 non-surgical (SM) and 2 surgical (SQ) departments. Type 1 and other specific types of diabetes, pregnancy and nutritional support were exclusion criteria. RESULTS: 288 patients were included for analysis (62.5% males; 70.3±10.3 years; 71.5% SM, 28.5% SQ). A scheduled subcutaneous insulin regimen based on basal-bolus-correction protocol was started in 55.9% (95%CI: 50.5-61.2%) of patients, 63.1% SM vs. 37.8% SQ (P<.05). Alternatives to insulin regimen based on basal-bolus-correction included sliding scale insulin (43.7%), diet (31.3%), oral antidiabetic drugs (17.2%), premixed insulin (1.6%), and others (6.2%). For patients previously on oral antidiabetic drugs, in-hospital insulin dose was 0.32±0.1 IU/kg/day. In patients previously on insulin, in-hospital insulin dose was increased by 17% [-13-53], and in those on insulin plus oral antidiabetic drugs, in-hospital insulin dose was increased by 26.4% [-6-100]. Supplemental insulin doses used for<40 IU/day and 40-80 IU/day were 72.2% and 56.7% respectively. HbA1c was measured in 23.6% of patients (95CI%: 18.8-28.8); 27.7% SM vs. 13.3% SQ (P<.05). CONCLUSIONS: Strategies are needed to improve implementation of the inpatient subcutaneous insulin protocol, particularly in surgical departments. Sliding scale insulin is still the most common alternative to insulin regimen based on basal-bolus-correction scheduled insulin. Metabolic control assessment during hospitalization should be encouraged.

Quantum chemical study of silanediols as metal binding groups for metalloprotease inhibitors.

DFT (B3LYP and M06L) as well as ab initio (MP2) methods with Dunning cc-pVnZ (n=2,3) basis sets are employed for the study of the binding ability of the new class of protease inhibitors, i.e., silanediols, in comparison to the well-known and well-studied class of inhibitors with hydroxamic functionality (HAM). Active sites of metalloproteases are modeled by [R3M-OH2]²âº complexes, where R stands for ammonia or imidazole molecules and M is a divalent cation, namely zinc, iron or nickel (in their different spin states). The inhibiting activity is estimated by calculating Gibbs free energies of the water displacement by metal binding groups (MBGs) according to: [R3M-OH2]²âº + MBG → [R3M-MBG]²âº + H2O. The binding energy of silanediol is only a few kcal mol(-1) inferior to that of HAM for zinc and iron complexes and is even slightly higher for the triplet state of the (NH3)3Ni²âº complex. For both MBGs studied in the ammonia model the binding ability is nearly the same, i.e., Fe²âº(t) > Ni²âº(t) > Fe²âº(q) > Ni²âº(s) > Zn²âº. However, for the imidazole model the order is slightly different, i.e., Ni²âº(t) > Fe²âº(t) > Fe²âº(q) > Ni²âº(s) ≥ Zn²âº. Equilibrium structures of the R3Zn ²âº complexes with both HAM and silanediol are characterized by the monodentate binding, but the bidentate character of binding increases on going to iron and nickel complexes. Two types of intermediates of the water displacement reactions for [(NH3)3M-OH2]²âº complexes were found which differ by the direction of the attack of the MBG. Hexacoordinated complexes exhibit bidentate bonding of MBGs and are lower in energy for M=Ni and Fe. For Zn penta- and hexacoordinated complexes have nearly the same energy. Intermediate complexes with imidazole ligands have only octahedral structures with bidentate bonding of both HAM and dimethylsilanediol molecules.

Resumen ejecutivo "Consenso sobre la evaluación y el tratamiento nutricional de los trastornos de la conducta alimentaria: anorexia nerviosa, bulimia nerviosa, trastorno por atracón y otros" / No disponible

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Consenso sobre la evaluación y el tratamiento nutricional de los trastornos de la conducta alimentaria: anorexia nerviosa / No disponible

La anorexia nerviosa es la enfermedad psiquiátrica más frecuente entre las mujeres jóvenes y se asume de origen multifactorial. Los criterios diagnósticos han sido recientemente modificados de forma que la amenorrea deja de formar parte de ellos. Esta enfermedad muestra una gran variabilidad en su presentación y gravedad, lo que condiciona diferentes abordajes terapéuticos y la necesidad de individualizar el tratamiento, haciéndose indispensable un enfoque multidisciplinar. Los objetivos persiguen restaurar el estado nutricional (a través de un plan dietético individualizado y basado en un patrón de consumo saludable), tratar las complicaciones y comorbilidades, la educación nutricional (basada en patrones alimentarios y nutricionales sanos), corrección de las conductas compensatorias y la prevención de recaídas. El tratamiento variará según la situación clínica del paciente, pudiendo realizarse en consultas externas (cuando existe estabilidad clínica), en hospital de día (modalidad intermedia entre el tratamiento ambulatorio tradicional y la hospitalización) o en hospitalización (fracaso del manejo ambulatorio o presencia de complicaciones médicas o psiquiátricas graves). La nutrición artificial a través del empleo de suplementos nutricionales orales, nutrición enteral y excepcionalmente nutrición parenteral puede ser necesaria en determinados escenarios clínicos. En pacientes severamente desnutridos se debe evitar el síndrome de realimentación. La anorexia nerviosa está asociada a numerosas complicaciones médicas que condicionan el estado de salud, la calidad de vida y que se relacionan estrechamente con la mortalidad. Existe poca evidencia clínica para evaluar los resultados de los distintos tratamientos en la anorexia nerviosa, estando basados la mayoría de las recomendaciones en consenso de expertos

Anorexia nervosa is the most common psychiatric disease among young women and it is assumed to be of multifactorial origin. Diagnostic criteria have recently been modified; therefore amenorrhea has ceased to be a part of them. This disease shows a large variability in its presentation and severity which conditions different therapeutic approaches and the need to individualize the treatment, thus it is indispensable a multidisciplinary approach. The goals are to restore nutritional status (through an individualized diet plan based on a healthy consumption pattern), treat complications and comorbidities, nutritional education (based on healthy eating and nutritional patterns), correction of compensatory behaviors and relapse prevention. The treatment will vary according to the patient's clinical situation, and it may be performed in outpatient clinics (when there is clinical stability), in a day hospital or ambulatory clinic (intermediate mode between traditional outpatient treatment and hospitalization) or hospitalization (when there is outpatient management failure or presence of serious medical or psychiatric complications). Artificial nutrition using oral nutritional supplements, enteral nutrition and exceptionally parenteral nutrition may be necessary in certain clinical settings. In severely malnourished patients the refeeding syndrome should be avoided. Anorexia nervosa is associated with numerous medical complications which determines health status, life quality, and is closely related to mortality. There is little clinical evidence to assess the results of different treatments in anorexia nervosa, when most of the recommendations are being based on expert consensus