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1.
Proc Natl Acad Sci U S A ; 120(25): e2209810120, 2023 06 20.
Article En | MEDLINE | ID: mdl-37307472

Patients with type 1 diabetes (T1D) suffer from insufficient functional ß-cell mass, which results from infiltration of inflammatory cells and cytokine-mediated ß-cell death. Previous studies demonstrated the beneficial effects of agonists of growth hormone-releasing hormone receptor (GHRH-R), such as MR-409 on preconditioning of islets in a transplantation model. However, the therapeutic potential and protective mechanisms of GHRH-R agonists on models of T1D diabetes have not been explored. Using in vitro and in vivo models of T1D, we assessed the protective propertie of the GHRH agonist, MR409 on ß-cells. The treatment of insulinoma cell lines and rodent and human islets with MR-409 induces Akt signaling by induction of insulin receptor substrate 2 (IRS2), a master regulator of survival and growth in ß-cells, in a PKA-dependent manner. The increase in cAMP/PKA/CREB/IRS2 axis by MR409 was associated with decrease in ß-cell death and improved insulin secretory function in mouse and human islets exposed to proinflammatory cytokines. The assessment of the effects of GHRH agonist MR-409 in a model of T1D induced by low-dose streptozotocin showed that mice treated with MR-409 exhibited better glucose homeostasis, higher insulin levels, and preservation of ß-cell mass. Increased IRS2 expression in ß-cells in the group treated with MR-409 corroborated the in vitro data and provided evidence for the underlying mechanism responsible for beneficial effects of MR-409 in vivo. Collectively, our data show that MR-409 is a novel therapeutic agent for the prevention and treatment of ß-cells death in T1D.


Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 1 , Pancreatic Neoplasms , Humans , Animals , Mice , Streptozocin , Cytokines , Insulin
2.
J Chem Phys ; 158(22)2023 Jun 14.
Article En | MEDLINE | ID: mdl-37309896

The incorporation of quantum dots in display technology has fueled a renewed interest in InP-based quantum dots, but difficulty controlling the Zn chemistry during shelling has stymied thick, even ZnSe shell growth. The characteristic uneven, lobed morphology of Zn-based shells is difficult to assess qualitatively and measure through traditional methods. Here, we present a methodological study utilizing quantitative morphological analysis of InP/ZnSe quantum dots to analyze the impact of key shelling parameters on InP core passivation and shell epitaxy. We compare conventional hand-drawn measurements with an open-source semi-automated protocol to showcase the improved precision and speed of this method. Additionally, we find that quantitative morphological assessment can discern morphological trends in morphologies that qualitative methods cannot. In conjunction with ensemble fluorescence measurements, we find that changes to shelling parameters that promote even shell growth often do so at the cost of core homogeneity. These results indicate that the chemistry of passivating the core and promoting shell growth must be balanced carefully to maximize brightness while maintaining emission color-purity.

3.
Elife ; 112022 06 28.
Article En | MEDLINE | ID: mdl-35762582

Members of the bacterial T6SS amidase effector (Tae) superfamily of toxins are delivered between competing bacteria to degrade cell wall peptidoglycan. Although Taes share a common substrate, they exhibit distinct antimicrobial potency across different competitor species. To investigate the molecular basis governing these differences, we quantitatively defined the functional determinants of Tae1 from Pseudomonas aeruginosa PAO1 using a combination of nuclear magnetic resonance and a high-throughput in vivo genetic approach called deep mutational scanning (DMS). As expected, combined analyses confirmed the role of critical residues near the Tae1 catalytic center. Unexpectedly, DMS revealed substantial contributions to enzymatic activity from a much larger, ring-like functional hot spot extending around the entire circumference of the enzyme. Comparative DMS across distinct growth conditions highlighted how functional contribution of different surfaces is highly context-dependent, varying alongside composition of targeted cell walls. These observations suggest that Tae1 engages with the intact cell wall network through a more distributed three-dimensional interaction interface than previously appreciated, providing an explanation for observed differences in antimicrobial potency across divergent Gram-negative competitors. Further binding studies of several Tae1 variants with their cognate immunity protein demonstrate that requirements to maintain protection from Tae activity may be a significant constraint on the mutational landscape of tae1 toxicity in the wild. In total, our work reveals that Tae diversification has likely been shaped by multiple independent pressures to maintain interactions with binding partners that vary across bacterial species and conditions.


Amidohydrolases , Peptidoglycan , Amidohydrolases/genetics , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/metabolism , Cell Wall/metabolism , Peptidoglycan/metabolism , Pseudomonas aeruginosa/metabolism
4.
Rev Argent Microbiol ; 53(2): 154-161, 2021.
Article En | MEDLINE | ID: mdl-33176955

St. Louis encephalitis (SLEV) and West Nile (WNV) arboviruses, which circulate in Argentina, are maintained in enzootic transmission cycles involving Culex mosquitoes (vectors) and birds belonging to orders Passeriformes and Columbiformes (amplifier hosts). The objective of this work was to determine the circulation of both viruses among wild birds in a semiarid ecosystem in the Province of La Rioja through a serologic survey. During spring 2013 and fall 2014, a total of 326 wild birds belonging to 41 species were captured in areas close to the cities of La Rioja and Chilecito, in the Province of La Rioja. While exposure to SLEV and WNV was analyzed in birds' serum through neutralizing antibody detection, viral circulation was estimated through apparent seroprevalence of neutralizing antibodies. The exposure of the avian community to viruses was 3.02% for SLEV and 1.89% for WNV, while 1.19% corresponded to coinfections. Our study confirms for the first time the circulation of SLEV and WNV in wild birds in the Province of La Rioja. Moreover, it is the first study to register neutralizing antibodies for flavivirus in the species Leptotila verreauxi (White-tipped Dove) (WNV) and Melanerpes cactorum (White-fronted Woodpecker) (SLEV). These results suggest that in semiarid ecosystems from northwestern Argentina the requirements and conditions for amplification and enzootic maintenance of SLEV and WNV would be present.


Encephalitis, St. Louis , West Nile virus , Animals , Antibodies, Viral , Argentina/epidemiology , Ecosystem , Encephalitis Virus, St. Louis , Encephalitis, St. Louis/epidemiology , Encephalitis, St. Louis/veterinary , Seroepidemiologic Studies
6.
Cell ; 183(6): 1562-1571.e12, 2020 12 10.
Article En | MEDLINE | ID: mdl-33306955

Ticks transmit a diverse array of microbes to vertebrate hosts, including human pathogens, which has led to a human-centric focus in this vector system. Far less is known about pathogens of ticks themselves. Here, we discover that a toxin in blacklegged ticks (Ixodes scapularis) horizontally acquired from bacteria-called domesticated amidase effector 2 (dae2)-has evolved to kill mammalian skin microbes with remarkable efficiency. Secreted into the saliva and gut of ticks, Dae2 limits skin-associated staphylococci in ticks while feeding. In contrast, Dae2 has no intrinsic ability to kill Borrelia burgdorferi, the tick-borne Lyme disease bacterial pathogen. These findings suggest ticks resist their own pathogens while tolerating symbionts. Thus, just as tick symbionts can be pathogenic to humans, mammalian commensals can be harmful to ticks. Our study underscores how virulence is context-dependent and bolsters the idea that "pathogen" is a status and not an identity.


Bacteria/metabolism , Immunologic Factors/metabolism , Ixodes/physiology , Skin/microbiology , Symbiosis , Animals , Anti-Bacterial Agents/pharmacology , Biocatalysis , Cell Wall/metabolism , Feeding Behavior , Female , Gastrointestinal Tract/metabolism , Host-Pathogen Interactions , Mice , Models, Molecular , Peptidoglycan/metabolism , Phylogeny , Saliva/metabolism , Salivary Glands/metabolism , Staphylococcus epidermidis/physiology , Structural Homology, Protein , Substrate Specificity , Up-Regulation
7.
J Vis Exp ; (145)2019 03 07.
Article En | MEDLINE | ID: mdl-30907885

The Solute Carrier 4 (SLC4) family of proteins is called the bicarbonate transporters and includes the archetypal protein Anion Exchanger 1 (AE1, also known as Band 3), the most abundant membrane protein in the red blood cells. The SLC4 family is homologous with borate transporters, which have been characterized in plants and fungi. It remains a significant technical challenge to express and purify membrane transport proteins to homogeneity in quantities suitable for structural or functional studies. Here we describe detailed procedures for the overexpression of borate transporters in Saccharomyces cerevisiae, isolation of yeast membranes, solubilization of protein by detergent, and purification of borate transporter homologs from S. cerevisiae, Arabidopsis thaliana, and Oryza sativa. We also detail a glutaraldehyde cross-linking experiment to assay multimerization of homomeric transporters. Our generalized procedures can be applied to all three proteins and have been optimized for efficacy. Many of the strategies developed here can be utilized for the study of other challenging membrane proteins.


Borates/metabolism , Eukaryotic Cells/metabolism , Membrane Transport Proteins/isolation & purification , Membrane Transport Proteins/metabolism , Arabidopsis/metabolism , Chromatography, Gel , Cross-Linking Reagents/metabolism , Ion Transport , Oryza/metabolism , Saccharomyces cerevisiae/metabolism , Solubility
8.
Eur Spine J ; 27(10): 2577-2583, 2018 10.
Article En | MEDLINE | ID: mdl-29995170

PURPOSE: Differentiating osteoporotic vertebral fractures (OVF) from metastatic vertebral fractures (MVF) is difficult. A magnetic resonance imaging (MRI)-based score (META score) aiming to differentiate OVF and MVF was recently published; however, an independent agreement assessment is required before the score is used. We performed such independent agreement evaluation, including raters with different levels of training. METHODS: Sixty-four patients with confirmed OVF or MVF were evaluated by six raters (three spine surgeons and three orthopaedic residents) using the META score. We used the intra-class correlation coefficient (ICC) to evaluate inter- and intra-observer agreement and the kappa statistic (κ) to determine the agreement for individual score criteria. We calculated the area under the receiver-operating characteristic curve (AUC) to establish the score accuracy. RESULTS: The inter-observer agreement was poor [ICC = 0.22 (0.12-0.33)]; spine surgeons [ICC = 0.75 (0.66-0.83)] had better agreement than that of residents [ICC = 0.06 (- 0.07 to 0.23)]. The intra-observer agreement was poor [ICC = 0.15 (- 0.04 to 0.30)]; both spine surgeons [ICC = 0.21 (0.05-0.41)] and residents exhibited poor agreement [ICC = - 0.06 (- 0.40 to 0.20)]. The agreement for each specific criterion varied from κ = 0.24 to κ = 0.38. The AUC was 0.57 (0.64 for spine surgeons and 0.51 for residents, p < 0.01). CONCLUSION: The inter-observer agreement using the META score was adequate for spine surgeons but not for residents; the intra-observer agreement was poor. These results do not support the standard use of the META score to differentiate OVF and MVF. These slides can be retrieved under Electronic Supplementary Material.


Diagnosis, Computer-Assisted/methods , Magnetic Resonance Imaging , Osteoporotic Fractures/diagnostic imaging , Spinal Fractures/diagnostic imaging , Diagnosis, Differential , Humans , Osteoporotic Fractures/surgery , ROC Curve , Spinal Fractures/surgery
9.
Eur J Med Chem ; 146: 621-635, 2018 Feb 25.
Article En | MEDLINE | ID: mdl-29407986

The present study seeks to describe the design and synthesis of six new Michael adducts of (1S,4S)-2,5-diazabicyclo[2.2.1]heptane-dithiocarbamate with nitrostyrenes and their in vitro antiproliferative activity against human cervical cancer cell lines [HeLa (HPV 18 positive), CaSki (HPV 16 positive) and ViBo (HPV negative) cervical cancer cell lines]. Virtual screening of the physicochemical properties of all compounds have also been presented. All the compounds exploited significant antiproliferative activity on the three cervical cancer cell lines. Compound 8a was found to be most potent, displaying in vitro antiproliferative activity against HeLa, CaSki and ViBo cervical cancer cell lines superior to Cisplatin and Paclitaxel with IC50 values 0.99 ±â€¯0.007, 2.36 ±â€¯0.016 and 0.73 ±â€¯0.002 µM respectively. In addition, compound 8a did not trigger the necrosis cell death to the test cancer cell lines. Further mechanistic study revealed that compound 8a could inhibit the cancer cell proliferation by inducing apoptosis through caspase-3 activation. Moreover, cell cycle analysis indicated that compound 8a could arrest the cell cycle at the G1 phase for HeLa and CaSki cancer cells. At the predetermined IC50 values on cancer cells, compound 8a did not induce any necrotic (cytotoxic) death to the normal human lymphocytes. In the present design, (1S,4S)-2,5-diazabicyclo[2.2.1]heptane system was found to be superior than the piperazine counterpart 11.


Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Aza Compounds/pharmacology , Nitro Compounds/pharmacology , Styrene/pharmacology , Thiocarbamates/pharmacology , Uterine Cervical Neoplasms/drug therapy , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Aza Compounds/chemistry , Cell Cycle/drug effects , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Female , HeLa Cells , Humans , Molecular Structure , Nitro Compounds/chemistry , Structure-Activity Relationship , Styrene/chemistry , Thiocarbamates/chemistry , Tumor Cells, Cultured , Uterine Cervical Neoplasms/pathology
10.
Biol Trace Elem Res ; 181(1): 38-43, 2018 Jan.
Article En | MEDLINE | ID: mdl-28500577

Pectins are a type of soluble fiber present in natural and processed foods. Evidence regarding the effect of esterification degree of pectins on iron absorption in humans is scarce. In the present study, the effect of pectins with different degrees of esterification on non-heme iron absorption in women was evaluated. A controlled experimental study was conducted with block design, involving 13 apparently healthy, adult women. Each subject received 5 mg Fe (FeSO4) without pectin (control) or accompanied by 5 g citrus pectin, two with a low degree of esterification (27 and 36%), and one with a high degree of esterification (67 to 73%), each on different days. Each day, the 5 mg Fe doses were marked with radioactive 59Fe or 55Fe. Radioactivity incorporated into erythrocytes was determined in blood samples 14 days after the marked Fe doses were consumed. On days 18 and 36 of study, 30 and 20 mL blood samples were obtained, respectively, and blood sample radioactivity incorporated into erythrocytes was determined. Body iron status was determined from blood taken on day 18. Whole body blood volume was estimated for calculate iron bioavailability; it was assumed that 80% of absorbed radioactivity was incorporated into the Hb. All women participants signed an informed consent of participation at baseline. Iron bioavailability (mean geometric ±1 SD) alone (control) was 18.2% (12.3-27.1%), iron + pectin27 was 17.2% (10.2-29.2%), iron + pectin36 was 15.3% (9.5-24.6%), and iron + pectin67 was 19.5% (10.0-38.0%). No statistically significant differences between iron bioavailability (repeated measures ANOVA, p = 0.22) were observed. Pectin esterification degree does not influence the bioavailability of non-heme iron in women.


Esters/metabolism , Iron/metabolism , Pectins/metabolism , Adult , Biological Availability , Esters/blood , Female , Humans , Iron/administration & dosage , Iron/blood , Middle Aged , Pectins/administration & dosage , Pectins/blood , Software
11.
PLoS One ; 12(9): e0184026, 2017.
Article En | MEDLINE | ID: mdl-28873091

The iron deficiency anaemia that often accompanies infection with Helicobacter pylori may reflect increased uptake of iron into gastric epithelial cells. Here we show an infection-associated increase in total intracellular iron levels was associated with the redistribution of the transferrin receptor from the cell cytosol to the cell surface, and with increased levels of ferritin, an intracellular iron storage protein that corresponded with a significant increase in lysosomal stores of labile iron. In contrast, the pool of cytosolic labile iron was significantly decreased in infected cells. These changes in intracellular iron distribution were associated with the uptake and trafficking of H. pylori through the cells, and enhanced in strains capable of expressing the cagA virulence gene. We speculate that degradation of lysosomal ferritin may facilitate H. pylori pathogenesis, in addition to contributing to bacterial persistence in the human stomach.


Epithelial Cells/metabolism , Epithelial Cells/pathology , Helicobacter Infections/microbiology , Helicobacter Infections/pathology , Helicobacter pylori/physiology , Homeostasis , Iron/metabolism , Stomach/pathology , Antigens, Bacterial/metabolism , Bacterial Proteins/metabolism , Cell Compartmentation , Cell Line, Tumor , Epithelial Cells/microbiology , Ferritins/metabolism , Humans , Lysosomes/metabolism , Mutation/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, Transferrin/genetics , Receptors, Transferrin/metabolism , rab GTP-Binding Proteins/metabolism , rab7 GTP-Binding Proteins
12.
Data Brief ; 11: 567-571, 2017 Apr.
Article En | MEDLINE | ID: mdl-28349104

We provide initial rate data from enzymatic reaction experiments and tis processing to estimate the kinetic parameters from the substrate uncompetitive inhibition equation using the median method published by Eisenthal and Cornish-Bowden (Cornish-Bowden and Eisenthal, 1974; Eisenthal and Cornish-Bowden, 1974). The method was denominated the direct linear plot and consists in the calculation of the median from a dataset of kinetic parameters Vmax and Km from the Michaelis-Menten equation. In this opportunity we present the procedure to applicate the direct linear plot to the substrate uncompetitive inhibition equation; a three-parameter equation. The median method is characterized for its robustness and its insensibility to outlier. The calculations are presented in an Excel datasheet and a computational algorithm was developed in the free software Python. The kinetic parameters of the substrate uncompetitive inhibition equation Vmax , Km and Ks were calculated using three experimental points from the dataset formed by 13 experimental points. All the 286 combinations were calculated. The dataset of kinetic parameters resulting from this combinatorial was used to calculate the median which corresponds to the statistic estimator of the real kinetic parameters. A comparative statistical analyses between the median method and the least squares was published in Valencia et al. [3].

13.
J Theor Biol ; 418: 122-128, 2017 04 07.
Article En | MEDLINE | ID: mdl-28130095

In 1974, Eisenthal and Cornish-Bowden published the direct linear plot method, which used the median to estimate the Vmax and Km from a set of initial rates as a function of substrate concentrations. The robustness of this non-parametric method was clearly demonstrated by comparing it with the least-squares method. The authors commented that the method cannot readily be generalized to equations of more than two parameters. Unfortunately, this comment has been misread by other authors. Comments such as "this method cannot be extended directly to equations with more than two parameters" were found in some publications. In addition, recently, the most drastic comment was published: "this method cannot be applied for the analysis of substrate inhibition." Given all of these presumptions, we have been motivated to publish a demonstration of the contrary: the median method can be applied to more than two-parameter equations, using as an example, the substrate uncompetitive inhibition equation. A computer algorithm was written to evaluate the effect of simulated experimental error of the initial rates on the estimation of Vmax, Km and KS. The error was assigned to different points of the experimental design. Four different KS/Km ratios were analyzed with the values 10, 100, 1000 and 10,000. The results indicated that the least-squares method was slightly better than the median method in terms of accuracy and variance. However, the presence of outliers affected the estimation of kinetic constants using the least-squares method more severely than the median method. The estimation of KS using the median method to estimate 1/KS was much better than the direct estimation of KS, causing a negative effect of non-linearity of KS in the kinetic equation. Considering that the median method is free from the assumptions of the least-squares method and the arbitrary assumptions implicit in the linearization methods to estimate the kinetic constants Vmax, Km and KS from the substrate uncompetitive inhibition equation, the median method is highly superior to all published methods, including the non-linear regression by least squares. We concluded that the median method can be applied to the substrate uncompetitive inhibition equation and other equations with more than two parameters. In addition, as we can project, the median method is the most reliable and robust method for the estimation of kinetic parameters from enzyme kinetic models.


Models, Chemical , Kinetics
14.
Medwave ; 16 Suppl 1: e6383, 2016 Mar 15.
Article En, Es | MEDLINE | ID: mdl-27028069

Thoracolumbar burst fractures account for up to 17% of major spinal fractures. Both conservative and operative treatments are widely used in clinical practice to manage thoracolumbar burst fractures. Previous studies showed good functional results with both treatments, but surgical approach has been associated with higher cost and risks of causing unnecessary adverse effects. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified 14 systematic reviews including 25 randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded that operative treatment may decrease the risk of neurologic impairment, but in turn, could increase the risk of general complications. It is unclear whether there are differences in pain reduction, improvement in function and quality of life, need for subsequent surgery or radiographic progression of kyphosis in both groups.


Las fracturas toracolumbares tipo burst representan hasta el 17% de las fracturas de columna.Se ha planteado tanto el tratamiento conservador como el quirúrgico para este tipo de fracturas, observando buenos resultados funcionales con ambos, pero con un mayor costo y riesgo de producir efectos adversos con la cirugía. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos seis revisiones sistemáticas que en conjunto incluyen cuatro estudios aleatorizados. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que el tratamiento quirúrgico podría disminuir el riesgo de deterioro neurológico pero con un mayor riesgo de complicaciones generales. Concluimos que no está claro si existen diferencias en dolor, funcionalidad, calidad de vida, necesidad de reintervención o progresión radiográfica de la cifosis entre el tratamiento conservador y el quirúrgico.


Pain/etiology , Quality of Life , Spinal Fractures/therapy , Databases, Factual , Humans , Lumbar Vertebrae/injuries , Postoperative Complications/epidemiology , Randomized Controlled Trials as Topic , Spinal Fractures/surgery , Thoracic Vertebrae/injuries , Treatment Outcome
15.
Food Chem ; 196: 733-8, 2016 Apr 01.
Article En | MEDLINE | ID: mdl-26593548

Forty-five women (35-45 year) were randomly assigned to three iron (Fe) absorption sub-studies, which measured the effects of dietary animal proteins on the absorption of heme Fe. Study 1 was focused on heme, red blood cell concentrate (RBCC), hemoglobin (Hb), RBCC+beef meat; study 2 on heme, heme+fish, chicken, and beef; and study 3 on heme and heme+purified animal protein (casein, collagen, albumin). Study 1: the bioavailability of heme Fe from Hb was similar to heme only (∼13.0%). RBCC (25.0%) and RBCC+beef (21.3%) were found to be increased 2- and 1.6-fold, respectively, when compared with heme alone (p<0.05). Study 2: the bioavailability from heme alone (10.3%) was reduced (p<0.05) when it was blended with fish (7.1%) and chicken (4.9%), however it was unaffected by beef. Study 3: casein, collagen, and albumin did not affect the bioavailability of Fe. Proteins from animal source foods and their digestion products did not enhance heme Fe absorption.


Dietary Proteins/metabolism , Heme/metabolism , Iron/metabolism , Meat/analysis , Proteins/metabolism , Adult , Animals , Biological Availability , Cattle , Chickens , Dietary Proteins/analysis , Digestion , Female , Fishes , Heme/analysis , Humans , Middle Aged , Proteins/analysis
16.
Medwave ; 15 Suppl 3: e6315, 2015 Nov 16.
Article En, Es | MEDLINE | ID: mdl-26610278

There are several nonsurgical alternatives to treat radicular pain in degenerative lumbar spinal stenosis. Epidural steroid injections have been used for several decades, but the different studies have shown variable effects. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified nine systematic reviews including seven pertinent randomized controlled trials. We concluded epidural steroid injection probably leads to little or no effect on reducing radicular pain of spinal stenosis.


Existe una variada cantidad de alternativas no quirúrgicas para tratar el dolor radicular producido por la raquiestenosis lumbar degenerativa. Los corticoides epidurales se utilizan desde hace varias décadas, sin embargo la eficacia reportada en la literatura es muy variable. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos nueve revisiones sistemáticas que en conjunto incluyen siete estudios aleatorizados. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que la inyección de corticoides epidurales probablemente tiene poco o nulo efecto en reducir el dolor radicular por estenorraquis.


Glucocorticoids/administration & dosage , Radiculopathy/drug therapy , Spinal Stenosis/drug therapy , Glucocorticoids/therapeutic use , Humans , Injections, Epidural , Lumbar Vertebrae , Radiculopathy/etiology , Randomized Controlled Trials as Topic , Spinal Stenosis/pathology
17.
Nutrients ; 7(11): 8977-86, 2015 Oct 30.
Article En | MEDLINE | ID: mdl-26529009

The aim of this study is to determine the effect of proteins from cereals and legumes on heme iron (Fe) absorption. The absorption of heme Fe without its native globin was measured. Thirty adult females participated in two experimental studies (15 per study). Study I focused on the effects of cereal proteins (zein, gliadin and glutelin) and study II on the effects of legume proteins (soy, pea and lentil) on heme Fe absorption. When heme was given alone (as a control), study I and II yielded 6.2% and 11.0% heme absorption (p > 0.05). In study I, heme Fe absorption was 7.2%, 7.5% and 5.9% when zein, gliadin and glutelin were added, respectively. From this, it was concluded that cereal proteins did not affect heme Fe absorption. In study II, heme Fe absorption was 7.3%, 8.1% and 9.1% with the addition of soy, pea and lentil proteins, respectively. Only soy proteins decreased heme Fe absorption (p < 0.05). These results suggest that with the exception of soy proteins, which decreased absorption, proteins derived from cereals and legumes do not affect heme Fe absorption.


Dietary Proteins/pharmacology , Edible Grain/chemistry , Fabaceae/chemistry , Heme/metabolism , Intestinal Absorption/drug effects , Iron/pharmacokinetics , Plant Proteins/pharmacology , Adult , Biological Availability , Diet , Female , Gliadin/pharmacology , Glutens/pharmacology , Humans , Iron, Dietary/pharmacokinetics , Lens Plant/chemistry , Pisum sativum/chemistry , Soybean Proteins/pharmacology , Glycine max/chemistry , Zein/pharmacology
18.
Biometals ; 28(1): 143-50, 2015 Feb.
Article En | MEDLINE | ID: mdl-25428685

Despite the evidence suggesting a role for Helicobacter pylori in the induction of systemic iron deficiency anaemia, little is known about the possibility of infection-associated changes in cellular iron homeostasis at the gastric epithelium. In this study we compared four different techniques for measuring iron in AGS cells, a gastric epithelial cell line that is widely used to model to H. pylori infection in vitro. Inductively coupled plasma-mass spectrometry proved to be an efficient method, but only when large numbers of cells were used. Two colorimetric assays that included the use of concentrated hydrochloric acid with or without potassium ferrocyanide detected iron in the micromolar but not the nanomolar range in cell-free standards. However, the third colorimetric assay that incorporated ferrozine proved to be highly accurate at detecting iron in the nanomolar range, and was able to detect iron in AGS cells, Moreover, using this assay, we were able to show that the level of iron in H. pylori-infected AGS cells is significantly increased when compared to uninfected cells.


Epithelial Cells/metabolism , Epithelial Cells/microbiology , Gastric Mucosa/cytology , Helicobacter pylori/pathogenicity , Iron/metabolism , Cell Line, Tumor , Helicobacter Infections/physiopathology , Humans
19.
Medwave ; 15 Suppl 3: e6330, 2015 Dec 07.
Article En, Es | MEDLINE | ID: mdl-26730585

Upper gastrointestinal bleeding constitutes a medical-surgical emergency given its important associated morbidity and mortality. The antifibrinolytic tranexamic acid might help stopping bleeding, but controversy remains about its role in this setting. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified five systematic reviews including eight randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded tranexamic acid probably decreases rebleeding and mortality, without increasing thromboembolic adverse effects in patients with upper gastrointestinal bleeding.


La hemorragia digestiva alta corresponde a una emergencia médico-quirúrgica debido a la alta morbilidad y mortalidad que conlleva. El ácido tranexámico, un antifibrinolítico, podría ayudar a lograr un control precoz del sangrado, sin embargo existe controversia sobre su real utilidad. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos cinco revisiones sistemáticas que en conjunto incluyen ocho estudios aleatorizados. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que el ácido tranexámico probablemente disminuye el resangrado y la mortalidad, y no aumenta los efectos adversos tromboembólicos en pacientes con hemorragia digestiva alta.


Antifibrinolytic Agents/therapeutic use , Gastrointestinal Hemorrhage/drug therapy , Tranexamic Acid/therapeutic use , Acute Disease , Antifibrinolytic Agents/adverse effects , Gastrointestinal Hemorrhage/prevention & control , Humans , Randomized Controlled Trials as Topic , Recurrence , Tranexamic Acid/adverse effects , Treatment Outcome
20.
Rev. chil. cardiol ; 33(3): 173-180, dic. 2014. tab
Article Es | LILACS | ID: lil-743819

Antecedentes: La efectividad de la aspiración de trombos de rutina en una angioplastía primaria (AP) es controversial. Objetivo: Evaluar la efectividad de la aspiración de rutinaria de trombos durante la AP en la preservación del flujo microvascular final, estratificada por horas de presentación. Métodos: Realizamos un ensayo clínico prospectivo randomizado de 122 pacientes que se presentaron al Hospital Sótero del Río con infarto agudo al miocardio con upradesnivel del ST (IAM c/SDST) a AP + aspiración o sólo AP, evaluando el flujo microvascular final. Resultados: Se randomizaron 59 pacientes a AP + aspiración y 63 a sólo AP En el grupo de aspiración hubo menor empleo de pre-dilatación (46.4% vs 80.3 por ciento; p=0.01) y menor necesidad de realizar técnicas complejas de bifurcación (3.6 por ciento vs 15.2 por ciento; p=0.03). No observamos diferencias en el flujo microvascular final medido por conteo de cuadros TIMI (cTFC) (25.6 +/- 11.8 vs 24.8 +/- 10.9; p=0.12). No hubo diferencias en el flujo microvascular final, de acuerdo al tiempo de presentación: < 3 horas de IAM c/SDST (cTFC 22.3 +/- -9.1 vs 22.4 +/--8; p= 0.2) y > 3 horas de IAM c/SDST (cTFC 27.7 +/- 13.4 vs 25.9 +/- 11.6; p= 0.08). Conclusion: En nuestra experiencia, no hay mejoría del flujo microvascular final en la tromboaspiración manual de rutina durante la AP como tampoco en el subgrupo de presentación precoz. La menor predilatación y el menor uso de técnicas complejas de bifurcación, podría traducir una angioplastía técnicamente más fácil al aspirar el trombo y permitir una mejor visualización del vasoculpable.


Background. There is controversy regarding the effectiveness of thrombi aspiration during primary angioplasty for ST elevation myocardial Aim: to evaluate the effect of routine aspiration of thrombus upon micro vascular flow, both overall and according to the time from initial pain to intervention. Method: 122 patients admitted to a general hospital for acute ST elevation myocardial infarction were prospectively randomized to undergo coronary angioplasty (PTCA) with prior aspiration of thrombi or PTCA alone. The final micro vascular flow was compared between groups. A similar analysis compared patients presenting before or after 3 hours from de initial pain. Results: 59 patients underwent thrombi aspiration followed by PTCA (A+PTCA) and 63 PTCA alone (PTCA). Compared to the PTCA group, the A+PTCA group required less frequently balloon pre-dilation. (46.4 percent vs 80.3 percent; p=0.01) and a need for complex angioplasty of bifurcation lesions (3.6 percent vs 15.2 percent; p=0.03). No difference was observed in final micro vascular flow assessed by cTFC between corresponding groups (25.6 +/- 11.8 vs 24.8 +/- 10.9; p=0.12). Compared to Group A+PTCA, patients undergoing PTCA alone had no difference in final micro vascular flow, irrespective of time from initial pain to PTCA: cTFC 22.3 +/- -9.1 vs 22.4 +/--8 in those treated <3 hours from initial pain and 27.7 +/- 13.4 vs 25.9 +/- 11.6, in those treated >= 3 hr after initial pain, respectively. Conclusion: Manual thrombi aspiration before PTCA in patients with ST elevation myocardial infarction did not improve micro vascular flow, regardless of the time from initial pain to primary PTCA. The lesser need for complex angioplasty and balloon pre-dilatation in patients undergoing thrombi aspiration may reflect a better visualization of affected arteries during PTCA.


Humans , Male , Female , Middle Aged , Angioplasty, Balloon, Coronary/methods , Myocardial Infarction/therapy , Thrombectomy/methods , Thrombosis/therapy , Myocardial Infarction/complications , Microcirculation , Prospective Studies , Suction , Time Factors
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