Morphological and functional aspects of the epidermis of the sea lamprey Petromyzon marinus throughout development.

The development of the epidermis of sea lamprey Petromyzon marinus along the whole life cycle was studied using conventional staining techniques and lectin histochemistry. The epidermis undergoes variations in morphology and thickness throughout development. The simple cuboidal epithelium found in the epidermis of prolarvae becomes stratified cubic in the adult by increasing the number of cell layers. The cuticle thickness undergoes a steady increase during the larval period. There are changes in the glycoconjugate composition of the three main cell types of the P. marinus epidermis, mucous, granular and skein cells, which are more pronounced after metamorphosis. The Alcian blue-periodic acid Schiff (AB-PAS) histochemical method shows the presence of both acidic and neutral glycoconjugates in the mucous cells, indicating their secretory function. Moreover, lectin analysis reveals a mucous secretion containing glycoconjugates such as sulphated glycosaminoglycans (N-acetylglucosamine and N-acetylgalactosamine) and N-glycoproteins rich in mannose. Although granular cells are AB-PAS negative, they exhibit a similar glycoconjugate composition to the mucous cells. Moreover, granular cells show sialic acid positivity in larvae but this monosaccharide residue is not detected after metamorphosis. The skein cells, a unique cell of lampreys, are negative to AB-PAS staining but they mostly contain l-fucose and sialic acid residues, which also disappear after metamorphosis. The function of the granular and skein cells is still unknown but the role of their glycoconjugate composition is discussed. In addition, a different cellular origin is suggested for these two types of cells.

Serum pyroglutamyl aminopeptidase activity: a promising novel biomarker candidate for liver cirrhosis.

OBJECTIVE: As a reflect of tissue damage, serum aminopeptidases have been proposed as biomarkers of various diseases. In order to search new serologic markers for liver cirrhosis we conducted a preliminary study in which we analyzed a broad range of aminopeptidase activities in serum of controls and patients diagnosed with pancreatitis, hepatitis, and liver cirrhosis without distinction among the etiological type or the degree of severity of each condition. METHODS: Alanyl-, arginyl-, glutamyl-, cystinyl- pyroglutamyl-, and aspartyl-aminopeptidase activities were analyzed fluorometrically, using aminoacyl-ß-naphthylamides as substrates. In addition, various parameters, such as alanine transaminase, aspartate transaminase, alkaline phosphatase, total bilirubin, direct bilirubin, and gamma glutamyl transpeptidase were assayed as routine laboratory test for liver function. RESULTS: Compared with control group, alanyl- and arginyl-aminopeptidase activities increased nonspecifically in pancreatitis, hepatitis and liver cirrhosis, glutamyl- and cystinyl-aminopeptidases did not differ between groups and pyroglutamyl-aminopeptidase demonstrated that while pancreatitis and hepatitis did not differ between them and with controls, this activity decreased selectively in liver cirrhosis compared with all the rest of groups (p<0.001 vs. control and p<0.01 vs. pancreatitis and hepatitis). Aspartyl-aminopeptidase also decreased significantly (p<0.05) in liver cirrhosis compared with controls. Routine parameters for liver function test increased, as expected, in the three pathologies analyzed. CONCLUSIONS: Despite the heterogeneous composition of the three patient groups, the specific reduction of the levels of pyroglutamyl-aminopeptidase activity in serum of liver cirrhosis patients might be considered as a potential candidate to be included in a combination of markers for the diagnosis of this disease.

Role of reactive oxygen species generation and Nod factors during the early symbiotic interaction between bradyrhizobia and peanut, a legume infected by crack entry.

AIMS: We evaluated whether reactive oxygen species (ROS) production and the plant antioxidant system are involved in the symbiotic interaction between bradyrhizobia and legumes infected by crack entry, without intracellular infection threads (IT) formation, such as Arachis hypogaea L. (peanut). The role of bradyrhizobial Nod factors (NF) in modulating the plants' oxidative burst was also analysed. METHODS AND RESULTS: Histochemical and quantitative procedures were used to detect ROS levels in inoculated and in NF-treated peanut roots. Increase in root H2O2 production was determined at 10 min postinoculation with Bradyrhizobium sp. SEMIA 6144 or after NF addition. ROS production was modulated by NF. From 15 to 30 min postinoculation, the compatibility of Bradyrhizobium sp.-peanut interaction depends mostly on the H2O2 detoxification via catalase. CONCLUSIONS: We demonstrated for the first time that the early events of the symbiotic interaction in legumes invaded by crack entry trigger an increase in ROS production (represented exclusively by a higher H2O2 content) in which NADPH-oxidase seems not to be involved. NF modulate this response by enhancing the plant antioxidant machinery, contributing to the creation of adequate conditions for symbiosis development. SIGNIFICANCE AND IMPACT OF THE STUDY: Our data provide new insights into the mechanism involves in the symbiotic interaction that establish legumes infected by crack entry and suggest that ROS response shows differences compared with legumes invaded by IT formation.

Diabetes mellitus tipo 2 en el paciente anciano institucionalizado / Type 2 diabetes mellitus in elderly institutionalized patients

Una mujer de 93 años de edad ingresa en una planta de hospitalización convencional por una infección respiratoria aguda. La paciente tiene diabetes mellitus tipo 2 de unos 15 años de evolución y no presenta otras comorbilidades asociadas, salvo progresiva dependencia por senescencia y un ingreso hospitalario previo por neumonía hace 6 meses; actualmente vive en una residencia asistida. En un análisis reciente tenía una HbA1c de 7,8%, con una creatinina sérica de 1,3mg/dl (MDRD: 45ml/min). Su tratamiento habitual consistía en glibenclamida 5mg al día y metformina 850mg cada 12h. ¿Qué pauta debemos seguir una vez hospitalizada? ¿Precisa de alguna modificación de su tratamiento al alta? (AU)

A 93-year-old woman is admitted to a conventional hospital ward for an acute respiratory infection. The patient has type 2 diabetes mellitus of approximately 15 years evolution and has no other associated comorbidities, except for progressive dependence due to senescence and a previous hospitalization for pneumonia 6 months ago. She is currently in an assisted-living residence. A recent laboratory test revealed an HbA1c level of 7.8%, with a serum creatinine level of 1.3mg/dl (MDRD, 45ml/min). Her standard treatment consists of 5mg of glibenclamide a day and 850mg of metformin every 12hours. What regimen should we follow once she is hospitalized? Does she require any change in her treatment at discharge? (AU)

Type 2 diabetes mellitus in elderly institutionalized patients. / Diabetes mellitus tipo 2 en el paciente anciano institucionalizado.

A 93-year-old woman is admitted to a conventional hospital ward for an acute respiratory infection. The patient has type 2 diabetes mellitus of approximately 15 years evolution and has no other associated comorbidities, except for progressive dependence due to senescence and a previous hospitalization for pneumonia 6 months ago. She is currently in an assisted-living residence. A recent laboratory test revealed an HbA1c level of 7.8%, with a serum creatinine level of 1.3mg/dl (MDRD, 45ml/min). Her standard treatment consists of 5mg of glibenclamide a day and 850mg of metformin every 12hours. What regimen should we follow once she is hospitalized? Does she require any change in her treatment at discharge?

Aproximación al manejo diagnóstico y terapéutico del síndrome de Charles Bonnet en un servicio de urgencias: una serie de 10 casos / Diagnostic and therapeutic management of Charles Bonnet syndrome in an emergency department: a description of 10 cases

Se expone el manejo diagnóstico y terapéutico del síndrome de Charles Bonnet (SCB)en urgencias. Estudio de una serie de casos de todos los casos atendidos por alucinaciones visuales que cumplían los criterios diagnósticos de SCB (introspección preservada, baja agudeza visual y ausencia de otros diagnósticos alternativos), en un servicio de urgencias de un hospital terciario y universitario durante 2 años (2010-2011). Posteriormente se realizó un seguimiento telefónico a los 6 meses para conocer la evolución clínica. De los 140 pacientes atendidos por alucinaciones visuales, 14 tuvieron como juicio clínico al alta de probable SCB, de los cuales sólo 10 cumplían los criterios diagnósticos de SBC. La edad media fue de 80,4 (DE 4,90) años, y 6 (60%) fueron mujeres. La sintomatología alucinatoria de presentación fue generalmente compleja (7 pacientes con visión de personas), y en la mayoría de los casos tenía una persistencia de escasos días (9pacientes con una duración de 1 a 4 días). En 8 (80%) de los casos la agudeza visual fue menor de 0,05 y en 3 (30%) tenían amaurosis en uno o ambos ojos. La exploración neurológica, los estudios analíticos, la radiografía simple no mostraron alteraciones de interés, y en aquellos 8 (80%) pacientes en los que se disponía de TC craneal, los hallazgos observados fueron inespecíficos. Se recomendaron medidas no farmacológicas en todos los casos y quetiapina 25 mg/día en 4 casos. El SCB se resolvió en menos de 3 meses en 6 (60%) de los pacientes. El SCB es una entidad que hay que tener en cuenta en los pacientes ancianos con pobre agudeza visual que consultan en urgencias por alucinaciones visuales. Su conocimiento puede resultar de interés a los urgenciólogos de cara a poder tranquilizar al paciente y evitar pruebas complementarias o tratamientos innecesarios con potenciales efectos adversos (AU)

To describe the diagnosis and therapeutic management of Charles Bonnet syndrome in the emergency department based on a retrospective descriptive study of all patients with visual hallucinations who were diagnosed with Charles Bonnet syndrome in the emergency department of Hospital Universitario Ramón y Cajal in 2010 and 2011. The patients met all the diagnostic criteria for this syndrome: preserved insight, diminished vision, and absence of an alternative diagnosis. Follow-up interviews were carried out by telephone an average of 6 months after diagnosis. Of a total of 140patients with visual hallucinations, 14 were discharged with a diagnosis of Charles Bonnet syndrome but only 10 met allthe diagnostic criteria. The mean (SD) age was 80.4 (4.90) years, and 60% were women. Complex visual hallucinations(of persons in 70%) had developed within 1 to 4 days of consultation in 90%. Visual acuity was less than 0.05 (hand movements or lights) for 80%, and 3 had full loss of vision in one or both eyes. Neurologic examination, laboratory tests, and a simple radiograph yielded no findings of interest. Computed tomography images of the head (70%) yieldedonly nonspecific findings. Hygienic measures and quetiapine (25 mg/d) were recommended for 4 patients. The syndrome resolved in less than 3 months in 60% of the patients. Charles Bonnet syndrome is relatively common among elderly patients with visual hallucinations and poor visual acuity, but the short-term prognosis is good. An understanding this syndrome is of great importance in emergency medicine, in the interest of avoiding unnecessary tests or treatments that may be harmful (AU)

Effect of crude glycerin on feed manufacturing, growth performance, plasma metabolites, and nutrient digestibility of growing-finishing pigs.

Three experiments were conducted to determine the effects of dietary addition of crude glycerin on pellet production efficiency and to evaluate its effect on growth performance and digestibility in growing-finishing pigs. Three dietary treatments were created by addition of 0, 2.5, or 5% crude glycerin to barley-soybean meal-based diet, and 4 batches of each dietary treatment (2 each for grower and finisher diets) were prepared. In the manufacturing process, crude glycerin supplementation linearly increased the feeder speed and production rate (P < 0.05), resulting in a 20 to 29% improvement in the feed production rate compared with the control. Production efficiency (kg/kWh) increased linearly (P < 0.05) as the level of crude glycerin in feed increased. A growth experiment was performed with 240 barrows (30 ± 1 kg initial BW) using a 2-phase feeding program over a 12-wk period with 4 pens per treatment and 20 pigs per pen. On the last day of the growth experiment, blood samples were collected to determine circulating glucose, fructosamine, and IGF-1 concentrations. Overall growth performance was not affected (P > 0.05) by dietary treatment, and there was no effect (P > 0.05) of dietary treatment on any plasma metabolite measured. A digestibility experiment involving 9 male pigs housed in metabolic cages was used to determine the coefficients of apparent fecal digestibility and N and mineral balances. Pigs were assigned to 1 of the 3 diets in each feeding period using a 3 × 3 Latin square arrangement of treatments (43 ± 3 and 74 ± 3 kg initial BW in the growing and finishing periods, respectively). In both feeding periods, fecal digestibility of OM and ether extract were affected by dietary treatment, increasing linearly (P < 0.05) with increasing crude glycerin levels. However, neither CP digestibility nor N retention was affected by the glycerin content in either the growing or finishing period. Digestibilities and balance of Ca and P showed opposite tendencies with the variations in crude glycerin content, which either decreased or increased depending on the feeding period. In conclusion, adding crude glycerin to the diet before pelleting improved feed mill production efficiency. The addition of crude glycerin up to 5% in the diet of growing-finishing pigs had no effect on growth performance, blood metabolites, nutrient digestibility, and N balance, but more studies are needed to determine how crude glycerin affects mineral metabolism and balance.

Pyrrolizidine alkaloids: their occurrence in Spanish honey collected from purple viper's bugloss (Echium spp.).

The incidence and concentration of pyrrolizidine alkaloids (PAs) from Echium spp. plant have been defined in 103 Spanish honey samples. Each sample was examined to determine total pollen content, the percentage of Echium spp. pollen, and simultaneous measurements of PAs and their N-oxides concentrations by the HPLC-ESI/MS method to identify the potential origin of PAs in honey. PAs were found in 94.2% of the raw honey samples analysed, in the range of 1-237 µg kg(-1) (average concentration = 48 µg kg(-1)). The PA pattern was clearly dominated by echimidine, lycopsamine and their N-oxides, representing the 97.8% of total ∑PAs, and only echimidine and echimidine-N-oxide surpassed the 87% of total ∑PA content. Others PAs, seneciphylline and heliotrine-N-oxide, appear to be reported in a lower incidence and concentration (average of 3 and 1 µg kg(-1), respectively). The Pearson Chi-squared test (p ≤ 0.01) confirms the non-correspondence between pollen plants and PA content. This study was also realised to generate a dataset in order to evaluate the potential risk of Spanish honeys containing PA plants belonging to the genera Echium.

High NaCl concentrations induce the nod genes of Rhizobium tropici CIAT899 in the absence of flavonoid inducers.

The nodulation (nod) genes of Rhizobium tropici CIAT899 can be induced by very low concentrations (micromolar to nanomolar range) of several flavonoid molecules secreted by the roots of leguminous plants under a number of different conditions. Some of these conditions have been investigated and appear to have a great influence on the concentration and the number of different Nod factors, which can induce root nodule primordia and pseudonodules in several leguminous plant roots. In one such condition, we added up to 300 mM NaCl to the induction medium of R. tropici CIAT899 containing the nod gene inducer apigenin. At the higher concentrations of NaCl, larger amounts and more different Nod factors were produced than in the absence of extra NaCl. To our surprise, under control conditions (300 mM NaCl without apigenin), some Nod-factor-like spots were also observed on the thin-layer plates used to detect incorporation of radiolabeled glucosamine into newly synthesized Nod factors. This phenomenon was further investigated with thin-layer plates, fusions of nod genes to the lacZ gene, high-performance liquid chromatography, mass spectrometry, and the formation of pseudonodules on bean roots. Here, we report that, in the absence of flavonoid inducers, high concentrations of NaCl induced nod genes and the production of Nod factors.

Effect of aluminum sulfate on litter composition and ammonia emission in a single flock of broilers up to 42 days of age.

New alternatives are necessary if the environmental impact linked to intensive poultry production is to be reduced, and different litter handling methods should be explored. Among these, acidifying amendments added to poultry litters has been suggested as a management practice to help reduce the potential environmental effect involved in multiple flock cycles. There have been several studies on the use of aluminum sulfate (alum) and its benefits, but almost no data are available under farm conditions in Europe. An experiment with Ross 308 broilers from 1 to 42 days of age was conducted to evaluate the effect of alum on litter composition, the solubility of some mineral elements and NH3 emission during a single flock-rearing period in commercial houses located in southeast Spain. Broilers were placed on clean wood shavings in four commercial houses, containing 20 000 broilers each. Before filling, alum was applied at a rate of 0.25 kg/m2 to the wood shavings of two poultry houses, whereas the remaining two were used as control. Litter from each poultry house was sampled every 3 to 5 days. Ammonia emissions from the poultry houses were monitored from 37 to 42 days of age. In comparison with the control group, alum treatment significantly reduced the pH level of the litter (P < 0.001) with an average difference of 1.32 ± 0.24 units. Alum-treated litter showed, on average, a higher electrical conductivity than the control litter (5.52 v. 3.63 dS/m). The dry matter (DM) and total N and P contents did not show differences between the treatments (P > 0.05). Regarding the NH4 +-N content, alum-treated litter showed a higher value than the untreated litter, with an average difference of 0.16 ± 0.07% (on a DM basis). On average, alum-treated litter had lower water-soluble P, Zn and Cu contents than the untreated litter. Alum noticeably reduced the in-house ammonia concentration (P < 0.001), with an average of 4.8 ppm at 42 days of age (62.9% lower than the control), and ammonia emissions from 37 to 42 days of age were significantly reduced by the alum treatment (P < 0.001), representing a reduction of 73.3%. The lower pH values might have reduced ammonia volatilization from the litter, with a corresponding positive effect on the building environment and poultry health. For these reasons, litter amendment with alum could be recommended as a way of reducing the pollution potential of European broiler facilities during a single flock cycle.

Effectiveness of holistic neuropsychological rehabilitation for Spanish population with acquired brain injury measured using Rasch analysis.

INTRODUCTION: The Rasch model is increasingly used in the field of rehabilitation because it improves the accuracy of measurements of patient status and their changes after therapy. OBJECTIVE: To determine the long-term effectiveness of a holistic neuropsychological rehabilitation program for Spanish outpatients with acquired brain injury (ABI) using Rasch analysis. METHODS: Eighteen patients (ten with long evolution - patients who started the program > 6 months after ABI- and eight with short evolution) and their relatives attended the program for 6 months. Patients' and relatives' answers to the European Brain Injury Questionnaire and the Frontal Systems Behavior Scale at 3 time points (pre-intervention. post-intervention and 12 month follow-up) were transformed into linear measures called logits. RESULTS: The linear measures revealed significant improvements with large effects at the follow-up assessment on cognitive and executive functioning, social and emotional self-regulation, apathy and mood. At follow-up, the short evolution group achieved greater improvements in mood and cognitive functioning than the long evolution patients. CONCLUSIONS: The program showed long-term effectiveness for most of the variables, and it was more effective for mood and cognitive functioning when patients were treated early. Relatives played a key role in the effectiveness of the rehabilitation program.

Effect of low-protein diets and single sex on production performance, plasma metabolites, digestibility, and nitrogen excretion in 1- to 48-day-old broilers.

Two experiments were conducted to investigate the effect of low-CP diets supplemented with crystalline amino acids, according to an ideal amino acid ratio, on the performance, plasma metabolites, nutrient digestibility, nitrogen balance, and water intake in male and female chickens from 1 to 48 d of age using a 4-phase feeding program: prestarter (1-7 d), starter (8-21 d), grower (22-35 d), and finisher (36-48 d). Three experimental diets were formulated for each phase: a control diet with a CP level of 24.5, 23.0, 21.5, and 20.5%, respectively, and medium- and low-CP diets containing 1.5 and 3% less than that of the control, respectively, but the same ME and digestible lysine levels. In experiment 1, in males, the reduction in dietary protein content by 3% increased the feed conversion ratio (P < 0.05) in the starter, grower, and finisher phases, and plasma albumin levels were reduced (P < 0.05) during the prestarter, starter, and finisher phases. In females, the same effect on plasma album levels was observed (P < 0.05) only in the starter phase. Sex affected plasma albumin levels during the prestarter, starter, and finisher phases, being higher in females. In experiment 2, the reduction in dietary protein content linearly decreased water consumption in both sexes (P < 0.05). The reduction of dietary protein by 1.5 or 3% reduced nitrogen excretion to the environment by 9.5 and 17% in males and by 11.8 and 14.6% in females, respectively. In summary, the low-CP 4-phase feeding reduced water intake and nitrogen excretion with an adverse effect on the feed conversion ratio in males but not in females. So, single-sex rearing could be used to reduce the environmental impact of chicken farms.

Effect of dietary crude protein levels in a commercial range, on the nitrogen balance, ammonia emission and pollutant characteristics of slurry in fattening pigs.

An experiment was conducted to investigate the effect of dietary levels of crude protein (CP), close to the range used commercially and to the European Commission recommended values, on the nitrogen (N) balance, ammonia (NH(3)) emission and pollutant characteristics of the slurry from growing and finishing pigs. Three feeding programmes with different CP levels were compared during the growing and the finishing periods of fattening. Diets were formulated to be isoenergetic and for the digestible lysine : metabolisable energy ratio to be similar in all the diets for each phase, but differed in CP concentration (160, 150 and 140 g CP/kg for the growing phase and 155, 145 and 135 g CP/kg for the finishing phase). Faeces and urine from barrows (eight replicates per diet) allocated in metabolism cages were collected separately for 5 days to calculate the N balance and for 2 days to measure NH(3) emission in a laboratory system for 240 h. Excreta were analysed for pH, volatile fatty acids (VFA), total N, electrical conductivity (EC), total solids (TS), volatile solids (VS), biochemical oxygen demand (BOD(5)), chemical oxygen demand (COD) and NH(4)-N reduction of dietary CP content led to a linear decrease of urinary (P < 0.05) and total (P < 0.05) N excretion, and N excretion/feed intake (P < 0.001). The emission of NH3 was similar in all diets (P > 0.05) during the 240 h of study. However, in the growing phase, the NH(3)-N level in slurry was lower (P < 0.05) for the low-CP diet. In addition, the CP level had no significant effect (P > 0.05) on total VFA, EC, TS, VS, COD or BOD(5) contents of excreta. These parameters were higher (P < 0.05) in slurry from the finishing phase than from the growing phase. However, NH(4)-N in the slurry decreased (P < 0.05) by 20.3% and 28.4% when the CP level was decreased by 9.30 or 21.40 g/kg, respectively. It is concluded that lowering dietary CP levels even by small amounts and using CP levels close to these used in commercial diets and close to the European Commission recommended values will decrease urinary and total N excretion in the slurry of growing-finishing pigs. The slurry from finishing pigs is more concentrated than that from growing pigs.

Inhibidores del cotransportador sodio-glucosa tipo 2(SGLT2): de la glucosuria renal familiar al tratamiento de la diabetes mellitus tipo 2 / Sodium-glucose cotransporter type 2 inhibitors (SGLT2): from familial renal glycosuria to the treatment of type 2 diabetes mellitus

Durante siglos, el riñón se ha considerado principalmente un órgano de eliminación y un regulador de la sal y del equilibrio iónico. A pesar de que una vez se pensó que era la causa estructural de la diabetes, y que en los últimos años ha sido ignorado como regulador de la homeostasis de la glucosa, actualmente es reconocido como un actor importante en el ámbito de la regulación del metabolismo glucídico. Durante el ayuno, el 55% de la glucosa proviene de la gluconeogénesis. Sólo 2 órganos tienen esta capacidad: el hígado y el riñón. Este último es responsable del 20% de la producción total deglucosa y del 40% de la producida por la gluconeogénesis. Hoy en día tenemos una mejor comprensión de la fisiología del transporte de glucosa renal a través de transportadores específicos, como el cotransportador sodio-glucosa tipo 2(SGLT2 por sus siglas en inglés: Sodium Glucose Cotransporter). Un compuesto natural, floricina, se aisló a principios de1800 y durante décadas desempeñó un papel importante enla diabetes y la investigación de la fisiología renal. Finalmente, en el nexo de estos descubrimientos antes mencionados, se reconoció el efecto de compuestos floricina-like en los transportadores de glucosa renal, lo que ha ofrecido un nuevo mecanismo para el tratamiento de la hiperglucemia. Esto ha llevado al desarrollo de varias modalidades terapéuticas potencialmente eficaces para el tratamiento de la diabetes (AU)

For centuries, the kidney has been considered primarily an organ of elimination and a regulator of salt and ion balance. Although once thought that the kidney was the structural cause of diabetes, which in recent years has been ignored as a regulator of glucose homeostasis, is now recognized as a major player in the field of metabolic regulation carbohydrate. During fasting, 55% of the glucose comes from gluconeogenesis. Only 2 organs have this capability: the liver and kidney. The latter is responsible for 20% of total glucose production and 40%of that produced by gluconeogenesis. Today we have a better understanding of the physiology of renal glucose transport via specific transporters, such as type 2 sodiumglucose cotransporter (SGLT2). A natural compound, phlorizin, was isolated in early 1800 and for decades played an important role in diabetes and renal physiology research. Finally, at the nexus of these findings mentioned above, recognized the effect of phlorizin-like compounds in the renal glucose transporter, which has offered a new mechanism to treat hyperglycemia. This has led to the development of several potentially effective treatment modalities for the treatment of diabetes (AU)

[Sodium-glucose cotransporter type 2 inhibitors (SGLT2): from familial renal glucosuria to the treatment of type 2 diabetes mellitus]. / Inhibidores del cotransportador sodio-glucosa tipo 2 (SGLT2): de la glucosuria renal familiar al tratamiento de la diabetes mellitus tipo 2.

For centuries, the kidney has been considered primarily an organ of elimination and a regulator of salt and ion balance. Although once thought that the kidney was the structural cause of diabetes, which in recent years has been ignored as a regulator of glucose homeostasis, is now recognized as a major player in the field of metabolic regulation carbohydrate. During fasting, 55% of the glucose comes from gluconeogenesis. Only 2 organs have this capability: the liver and kidney. The latter is responsible for 20% of total glucose production and 40% of that produced by gluconeogenesis. Today we have a better understanding of the physiology of renal glucose transport via specific transporters, such as type 2 sodium-glucose cotransporter  (SGLT2). A natural compound, phlorizin, was isolated in early 1800 and for decades played an important role in diabetes and renal physiology research. Finally, at the nexus of these findings mentioned above, recognized the effect of phlorizin-like compounds in the renal glucose transporter, which has offered a new mechanism to treat hyperglycemia. This has led to the development of several potentially effective treatment modalities for the treatment of diabetes.

Cellular localization and distribution of dopamine D(4) receptors in the rat cerebral cortex and their relationship with the cortical dopaminergic and noradrenergic nerve terminal networks.

The role of the dopamine D(4) receptor in cognitive processes and its association with several neuropsychiatric disorders have been related to its preferential localization in the cerebral cortex. In the present work we have studied in detail the regional and cellular localization of the dopamine D(4) receptor immunoreactivity (IR) in the rat cerebral cortex and its relationship to the dopaminergic and noradrenergic nerve terminal networks, since both dopamine and noradrenaline have a high affinity for this receptor. High levels of D(4) IR were found in motor, somatosensory, visual, auditory, temporal association, cingulate, retrosplenial and granular insular cortices, whereas agranular insular, piriform, perirhinal and entorhinal cortices showed low levels. D(4) IR was present in both pyramidal and non-pyramidal like neurons, with the receptor being mainly concentrated to layers II/III. Layer I was observed to be exclusively enriched in D(4) IR branches of apical dendrites. Finally, mismatches were observed between D(4) IR and tyrosine hydroxylase and dopamine beta-hydroxylase IR nerve terminal plexuses, indicating that these receptors may be activated at least in part by dopamine and noradrenaline operating as volume transmission signals. The present findings support a major role of the dopamine D(4) receptor in mediating the transmission of cortical dopamine and noradrenaline nerve terminal plexuses.

Identification and characterization of a nodH ortholog from the alfalfa-nodulating Or191-like rhizobia.

Nodulation of Medicago sativa (alfalfa) is known to be restricted to Sinorhizobium meliloti and a few other rhizobia that include the poorly characterized isolates related to Rhizobium sp. strain Or191. Distinctive features of the symbiosis between alfalfa and S. meliloti are the marked specificity from the plant to the bacteria and the strict requirement for the presence of sulfated lipochitooligosaccharides (Nod factors [NFs]) at its reducing end. Here, we present evidence of the presence of a functional nodH-encoded NF sulfotransferase in the Or191-like rhizobia. The nodH gene, present in single copy, maps to a high molecular weight megaplasmid. As in S. meliloti, a nodF homolog was identified immediately upstream of nodH that was transcribed in the opposite direction (local synteny). This novel nodH ortholog was cloned and shown to restore both NF sulfation and the Nif+Fix+ phenotypes when introduced into an S. meliloti nodH mutant. Unexpectedly, however, nodH disruption in the Or191-like bacteria did not abolish their ability to nodulate alfalfa, resulting instead in a severely delayed nodulation. In agreement with evidence from other authors, the nodH sequence analysis strongly supports the idea that the Or191-like rhizobia most likely represent a genetic mosaic resulting from the horizontal transfer of symbiotic genes from a sinorhizobial megaplasmid to a not yet clearly identified ancestor.

Potential of carvacrol to modify in vitro rumen fermentation as compared with monensin.

The aim of this study was to assess the effect of carvacrol supplement as a dietary additive to rumen fermentors, fed a barley seed:alfalfa hay (70:30) ration and to compare its effect with monensin supplementation. The material was incubated with goat ruminal fluid and four different treatments were included: no additive (C), 7.5 mg/l monensin (M), 250 mg/l carvacrol (C250) and 500 mg/l carvacrol (C500). The addition of carvacrol reduced in vitro dry matter (DM), crude protein (CP) and neutral-detergent fibre (NDF) digestion. The effects induced by C250 on DM digestion at 72 h of incubation were comparable with those of M, whereas a greater reduction was obtained when carvacrol was supplemented at 500 mg/l concentration (68.9, 68.5 and 53.0 v. 76.1% for M, C250 and C500 v. C, respectively). The reduced CP potential degradability by supplements (51.2, 53.9 and 51.5 v. 72.8% for M, C250 and C500 v. C, respectively) was mainly caused by a reduction of the slowly degradable fraction. Volatile fatty acid (VFA) profiles determined after 48 h of incubation showed C250 increased butyrate and decreased acetate proportions, whereas M mainly stimulated propionate proportions, suggesting that the mechanism of action of carvacrol and M differs. C500 significantly reduced total VFA production. Carvacrol could be of great interest for its usage as a potential modulator of ruminal fermentation. Future research, including in vivo studies, in order to understand the factors that contribute to its antimicrobial activity and the selection of the optimal dose is required.

Evaluación fermentativa del ensilado del subproducto de alcachofa (Cynara scolymus L. ) en tres niveles de un microsilo / Fermentative evaluation of the artichoke (Cynara scolymus L. ) by-product ensilage on three levels of microsilo

Se ha estudiado la evolución de indicadores fermentativos durante 50 días de ensilaje en el subproductoagroindustrial de alcachofa (Cynara scolymus, L). Las muestras se analizaron a intervalos regulares de tiempo(1, 2, 3, 4, 8, 12, 24 y 50 días), en tres fracciones del microsilo (inferior, medio y superior). El pH se estabilizóen los primeros 12 días de fermentación. El contenido de ácido láctico y acético fue diferente entre los días defermentación (p<0,001), pero las diferencias entre fracciones no fue significativa. El contenido de hidratos de carbono solubles fue diferente solo entre los diferentes días de ensilaje (p<0,001). Los resultados demuestran que no existen cambios estadísticamente signifi cativos entre las fracciones evaluadas demostrando un buen nivel fermentativo del ensilaje. Se puede concluir que el subproducto crudo de alcachofa es un material muy idóneo para ser conservado mediante ensilaje

The fermentative indicators evolution has been studied during 50 days of silage in the agro-industrial artichokeby-product (Cynara scolymus, L). The samples were analyzed at different sampling days (1, 2, 3, 4, 8,12, 24 and 50), in three fractions of the microsilo (botton, medium and top). The pH stabilized in the first 12 days. The lactic and acetic acids content was different between the sampling days (p<0.001), but the differences between fractions were not significatives. Water soluble carbohydrates content was different between the different ensiling days (p<0.001). No changes on pH have found and lactic or acetic acids and water solublecarbohydrates between the fractions evaluated. We can conclude that crude artichoke by-product will be suitableto be conserved by ensilage

Effect of thyme essential oils (Thymus hyemalis and Thymus zygis) and monensin on in vitro ruminal degradation and volatile fatty acid production.

The effect of the essential oils of thyme on the in vitro ruminal degradability of a barley seed/alfalfa hay substrate was studied. Two essential oils were used, one from Thymus hyemalis (TH), rich in carvacrol, and the other from Thymus zygis (TZ), rich in thymol. Four experimental treatments of in vitro degradability, using the Daisy II(200/220) incubator, were conducted including a negative control (CO), a positive control at 7.5 microg/mL of monensin (MO), and two treatments with essential oils (TH or TZ) at 1.35 microL/mL. The material was incubated at 39.5 degrees C for various lengths of time. At each time, the disappearance of dry matter, crude protein, and neutral detergent fiber was measured. Volatile fatty acids (VFAs) were determined after 48 h of incubation. CO and MO provided (p < 0.01) higher values of potential degradability (a + b) of DM than the TH and TZ treatments (72.6 and 70.8 vs 53.2 and 48.2%, respectively). Also, crude protein degradability was lowest in the essential oil treatments. The CO treatment showed the highest potential degradability of NDF. The values of VFA production obtained (p < 0.001) with CO and MO treatments were higher than those obtained with TH and TZ treatments (21.0 and 19.1 vs 11.2 and 10.1 mM). The essential oils decreased the molar proportion of propionate, increasing the acetate/propionate ratio. In conclusion, the effects of essential oils at assayed doses would not be nutritionally beneficial to the ruminal energetic metabolism.