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1.
Int J Mol Sci ; 22(16)2021 Aug 15.
Article in English | MEDLINE | ID: mdl-34445459

ABSTRACT

An understanding of the immune mechanisms that lead to rejection versus tolerance of allogeneic pancreatic islet grafts is of paramount importance, as it facilitates the development of innovative methods to improve the transplant outcome. Here, we used our established intraocular islet transplant model to gain novel insight into changes in the local metabolome and proteome within the islet allograft's immediate microenvironment in association with immune-mediated rejection or tolerance. We performed integrated metabolomics and proteomics analyses in aqueous humor samples representative of the graft's microenvironment under each transplant outcome. The results showed that several free amino acids, small primary amines, and soluble proteins related to the Warburg effect were upregulated or downregulated in association with either outcome. In general, the observed shifts in the local metabolite and protein profiles in association with rejection were consistent with established pro-inflammatory metabolic pathways and those observed in association with tolerance were immune regulatory. Taken together, the current findings further support the potential of metabolic reprogramming of immune cells towards immune regulation through targeted pharmacological and dietary interventions against specific metabolic pathways that promote the Warburg effect to prevent the rejection of transplanted islets and promote their immune tolerance.


Subject(s)
Graft Rejection/metabolism , Insulin-Secreting Cells/metabolism , Islets of Langerhans Transplantation , Metabolomics , Proteomics , Transplantation Tolerance , Allografts , Animals , Graft Rejection/pathology , Insulin-Secreting Cells/pathology , Male , Mice
2.
Gac Med Mex ; 157(3): 325-334, 2021.
Article in English | MEDLINE | ID: mdl-34667327

ABSTRACT

Medical education has implemented various innovative strategies with the purpose to attain better learning achievements. An evaluation is made of the experiences in the competencies approach, new learning technologies, curricular alternatives, professional evaluation and distance education technologies in order to locate them in the areas they belong.


La educación médica ha puesto en práctica diversas estrategias innovadoras con el propósito de alcanzar mejores logros de aprendizaje. Se hace una evaluación de las experiencias relacionadas con el enfoque por competencias, las nuevas tecnologías educativas, las alternativas curriculares, la profesionalización de la evaluación y las técnicas educativas a distancia, para ubicarlas en el lugar que les corresponde.


Subject(s)
Education, Distance , Education, Medical , Curriculum , Humans , Learning
3.
Gac Med Mex ; 156(4): 311-316, 2020.
Article in English | MEDLINE | ID: mdl-32831322

ABSTRACT

Medical schools play a central role in the compilation and development of professional knowledge, which is why they have privileges and resources that are justified only to the extent that they use them to serve the community, particularly those who are most in need. Medical schools social accountability focuses on the training, healthcare provision and research services they offer. The principles of medical education and the structure proposed by the Flexner Report are in crisis due to the COVID-19 pandemic, and redefinition of the social contract is required. This document offers a proposal for medical schools social accountability that includes anticipation of the needs of the community, patient-centered inter-professional care, training of people in the area of health and collaboration between institutions. It highlights the need for a conscious institution that finds new training spaces other than hospitals, where each patient is cared for in a personalized way, with inter-professional training models that consider the student as a person who takes care of him/herself in open collaboration with organizations. Leaders must act now because it is their social accountability and because it is the right thing to do.


Las escuelas de medicina desempeñan un papel central en la acumulación y desarrollo del conocimiento profesional, por lo cual poseen privilegios y recursos que se justifican solo en la medida en que los retribuyan a la comunidad, en particular a los más necesitados. La responsabilidad social de las escuelas de medicina se centra en los servicios formativos, asistenciales y de investigación que ofrecen. Los principios de la educación médica y la estructura propuesta por el Informe Flexner están en crisis debido a la pandemia de COVID-19 y se requiere la redefinición del contrato social. El presente documento ofrece una propuesta de responsabilidad social de las escuelas de medicina que incluye previsión de las necesidades de la comunidad, atención interprofesional centrada en el paciente, formación de profesionales en el área de salud y colaboración entre instituciones. Resalta la necesidad de una institución consciente que encuentre nuevos espacios de entrenamiento diferentes al hospitalario, donde se atienda a cada paciente de forma personalizada, con modelos formativos interprofesionales que consideren al alumno como persona que cuida de sí misma en colaboración abierta con las organizaciones. Los líderes deben actuar ya porque es su responsabilidad social y porque es lo correcto.


Subject(s)
Coronavirus Infections/therapy , Education, Medical/methods , Pneumonia, Viral/therapy , Social Responsibility , COVID-19 , Cooperative Behavior , Coronavirus Infections/epidemiology , Delivery of Health Care/organization & administration , Humans , Pandemics , Patient-Centered Care/methods , Pneumonia, Viral/epidemiology , Schools, Medical , Students, Medical
4.
Diabetologia ; 62(7): 1237-1250, 2019 07.
Article in English | MEDLINE | ID: mdl-31087105

ABSTRACT

AIMS/HYPOTHESIS: Autoimmune attack against the insulin-producing beta cells in the pancreatic islets results in type 1 diabetes. However, despite considerable research, details of the type 1 diabetes immunopathology in situ are not fully understood mainly because of difficult access to the pancreatic islets in vivo. METHODS: Here, we used direct non-invasive confocal imaging of islets transplanted in the anterior chamber of the eye (ACE) to investigate the anti-islet autoimmunity in NOD mice before, during and after diabetes onset. ACE-transplanted islets allowed longitudinal studies of the autoimmune attack against islets and revealed the infiltration kinetics and in situ motility dynamics of fluorescence-labelled autoreactive T cells during diabetes development. Ex vivo immunostaining was also used to compare immune cell infiltrations into islet grafts in the eye and kidney as well as in pancreatic islets of the same diabetic NOD mice. RESULTS: We found similar immune infiltration in native pancreatic and ACE-transplanted islets, which established the ACE-transplanted islets as reliable reporters of the autoimmune response. Longitudinal studies in ACE-transplanted islets identified in vivo hallmarks of islet inflammation that concurred with early immune infiltration of the islets and preceded their collapse and hyperglycaemia onset. A model incorporating data on ACE-transplanted islet degranulation and swelling allowed early prediction of the autoimmune attack in the pancreas and prompted treatments to intercept type 1 diabetes. CONCLUSIONS/INTERPRETATION: The current findings highlight the value of ACE-transplanted islets in studying early type 1 diabetes pathogenesis in vivo and underscore the need for timely intervention to halt disease progression.


Subject(s)
Diabetes Mellitus, Type 1/diagnostic imaging , Animals , Autoimmunity/physiology , Diabetes Mellitus, Type 1/immunology , Diabetes Mellitus, Type 1/surgery , Graft Survival/physiology , Insulin-Secreting Cells/immunology , Insulin-Secreting Cells/metabolism , Islets of Langerhans/surgery , Islets of Langerhans Transplantation , Mice , Mice, Inbred NOD
5.
Diabetologia ; 62(5): 811-821, 2019 05.
Article in English | MEDLINE | ID: mdl-30701283

ABSTRACT

AIMS/HYPOTHESIS: Patients with autoimmune type 1 diabetes transplanted with pancreatic islets to their liver experience significant improvement in quality of life through better control of blood sugar and enhanced awareness of hypoglycaemia. However, long-term survival and efficacy of the intrahepatic islet transplant are limited owing to liver-specific complications, such as immediate blood-mediated immune reaction, hypoxia, a highly enzymatic and inflammatory environment and locally elevated levels of drugs including immunosuppressive agents, all of which are injurious to islets. This has spurred a search for new islet transplant sites and for innovative ways to achieve long-term graft survival and efficacy without life-long systemic immunosuppression and its complications. METHODS: We used our previously established approach of islet transplant in the anterior chamber of the eye in allogeneic recipient mouse models and a baboon model of diabetes, which were treated transiently with anti-CD154/CD40L blocking antibody in the peri-transplant period. Survival of the intraocular islet allografts was assessed by direct visualisation in the eye and metabolic variables (blood glucose and C-peptide measurements). We evaluated longitudinally the cytokine profile in the local microenvironment of the intraocular islet allografts, represented in aqueous humour, under conditions of immune rejection vs tolerance. We also evaluated the recall response in the periphery of the baboon recipient using delayed-type hypersensitivity (DTH) assay, and in mice after repeat transplant in the kidney following initial transplant with allogeneic islets in the eye or kidney. RESULTS: Results in mice showed >300 days immunosuppression-free survival of allogeneic islets transplanted in the eye or kidney. Notably, >70% of tolerant mice, initially transplanted in the eye, exhibited >400 days of graft survival after re-transplant in the kidney without immunosuppression compared with ~30% in mice that were initially transplanted in the kidney. Cytokine and DTH data provided evidence of T helper 2-driven local and peripheral immune regulatory mechanisms in support of operational immune tolerance towards the islet allografts in both models. CONCLUSIONS/INTERPRETATION: We are currently evaluating the safety and efficacy of intraocular islet transplantation in a phase 1 clinical trial. In this study, we demonstrate immunosuppression-free long-term survival of intraocular islet allografts in mice and in a baboon using transient peri-transplant immune intervention. These results highlight the potential for inducing islet transplant immune tolerance through the intraocular route. Therefore, the current findings are conceptually significant and may impact markedly on clinical islet transplantation in the treatment of diabetes.


Subject(s)
Diabetes Mellitus, Type 1/immunology , Islets of Langerhans Transplantation , Islets of Langerhans/cytology , Transplantation Tolerance , Animals , Cytokines/metabolism , Female , Graft Rejection/immunology , Graft Survival/immunology , Hypoglycemia/immunology , Hypoxia , Immunosuppression Therapy , Immunosuppressive Agents , Inflammation , Male , Mice , Mice, Inbred C57BL , Mice, Inbred DBA , Papio/immunology , Transplantation, Homologous , Treatment Outcome
7.
J Clin Lab Anal ; 31(6)2017 Nov.
Article in English | MEDLINE | ID: mdl-28169465

ABSTRACT

BACKGROUND: Preterm neonates exhibit several deficiencies that endanger their lives. Understanding those disturbances will provide tools for the management of preterm neonates. The present work focuses on arginine and citrulline which has been flagged among the biochemical landmarks of prematurity. METHODS: We examined blood samples of preterm newborns as compared with mature neonates to determine the levels of arginine and citrulline by capillary zone electrophoresis with laser induced fluorescence detection (CZE-LIFD). RESULTS: Significantly lower levels of arginine and citrulline were found in preterm neonates than in mature neonates (P<.01). Interestingly there was a highly significant correlation between the two amino acids in mature neonates (P<.0001). Such correlation was present in preterm neonates too (P<.01). Pearson coefficient showed that 60% of the citrulline concentration depends on arginine concentration in mature neonates. Only 20% of the citrulline concentration depends on arginine concentration in preterm neonates. Although the ratio arginine/citrulline was lower in preterm neonates than in mature neonates the difference was not statistically significant. CONCLUSIONS: These results suggest that less arginine is converted to citrulline to form nitric oxide in preterm than in full-term neonates. The result is discussed in terms of the immature enzymatic systems in the preterm neonate.


Subject(s)
Arginine/blood , Citrulline/blood , Infant, Premature, Diseases/blood , Infant, Premature, Diseases/epidemiology , Infant, Premature/blood , Cohort Studies , Electrophoresis, Capillary , Female , Humans , Infant, Newborn , Infant, Newborn, Diseases/blood , Infant, Newborn, Diseases/epidemiology , Male , Nitric Oxide , Spectrometry, Fluorescence
8.
Mutat Res ; 742(1-2): 66-71, 2012 Feb 18.
Article in English | MEDLINE | ID: mdl-22198330

ABSTRACT

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants presenting a public health risk, particularly to children, a vulnerable population. PAHs have genotoxic and carcinogenic properties, which depend on their metabolism. Many enzymes involved in PAH metabolism, including CYP1A1, CYP1B1, GSTM and GSTT are polymorphic, which may modulate the activation/deactivation of these compounds. We evaluated PAH exposure and DNA damage in children living in the vicinity of the main petrochemical complex located in the Gulf of Mexico, and explored the modulation by genetic polymorphisms of PAH excretion and related DNA damage. The participants (n=82) were children aged 6-10y attending schools near the industrial area. Urinary 1-hydroxypyrene (1-OHP; a biomarker of PAH exposure) was determined by reverse-phase-HPLC; DNA damage by the comet assay (Olive Tail Moment (OTM) parameter); CYP1A1*2C and CYP1B1*3 polymorphisms by real time-PCR; and GSTM1*0 and GSTT1*0 by multiplex PCR. The median value of 1-OHP was 0.37µmol/mol creatinine; 59% of children had higher 1-OHP concentrations than those reported in environmentally exposed adults (0.24µmol/mol creatinine). A stratified analysis showed increased DNA damage in children with 1-OHP concentrations greater than the median value. We observed higher 1-OHP concentrations in children with CYP1A1*2C or GSTM1*0 polymorphisms, and a positive influence of CYP1A1*2C on OTM values in children with the highest PAH exposure. The data indicate that children living in the surroundings of petrochemical industrial areas are exposed to high PAH levels, contributing to DNA damage and suggesting an increased health risk; furthermore, data suggest that polymorphisms affecting activation enzymes may modulate PAH metabolism and toxicity.


Subject(s)
DNA Damage/drug effects , Environmental Exposure , Polycyclic Aromatic Hydrocarbons/toxicity , Child , Cytochrome P-450 CYP1A1/genetics , Female , Humans , Male , Mexico , Polycyclic Aromatic Hydrocarbons/metabolism , Polymorphism, Genetic , Pyrenes/pharmacokinetics
9.
Front Biosci (Schol Ed) ; 14(2): 14, 2022 05 09.
Article in English | MEDLINE | ID: mdl-35730439

ABSTRACT

Chronic kidney disease is generally progressive and currently has no reliable treatment to reverse a decline in kidney function or to slow the progression of the disease. Diabetic nephropathy is one of the leading causes of end-stage kidney failure. Kidney damage in diabetic nephropathy is largely attributed to the increased oxidative stress, affecting its metabolic activity, metabolic pathways, and hemodynamic pathways. In diabetic patients, hyperglycemia causes an increase in the production of reactive oxygen species that further increase oxidative stress. These reactive oxygen species are created through a variety of pathways, providing the opportunity for treatment using anti-oxidative defense mechanisms to prevent vascular injury. This review will give an overview of oxidative stress, along with the current treatments and limitations of diabetic nephropathy. We will also discuss the potential of antioxidative therapies, with an emphasis on the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway.


Subject(s)
Diabetes Mellitus , Diabetic Nephropathies , Hyperglycemia , Antioxidants/metabolism , Antioxidants/pharmacology , Antioxidants/therapeutic use , Diabetes Mellitus/metabolism , Diabetic Nephropathies/drug therapy , Diabetic Nephropathies/metabolism , Humans , Hyperglycemia/metabolism , Kidney/metabolism , Oxidative Stress , Reactive Oxygen Species/metabolism
10.
Biomedicines ; 10(2)2022 Feb 17.
Article in English | MEDLINE | ID: mdl-35203680

ABSTRACT

Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia as a result of insufficient insulin levels and/or impaired function as a result of autoimmune destruction or insulin resistance. While Type 1 DM (T1DM) and Type 2 DM (T2DM) occur through different pathological processes, both result in ß-cell destruction and/or dysfunction, which ultimately lead to insufficient ß-cell mass to maintain normoglycemia. Therefore, therapeutic agents capable of inducing ß-cell proliferation is crucial in treating and reversing diabetes; unfortunately, adult human ß-cell proliferation has been shown to be very limited (~0.2% of ß-cells/24 h) and poorly responsive to many mitogens. Furthermore, diabetogenic insults result in damage to ß cells, making it ever more difficult to induce proliferation. In this review, we discuss ß-cell mass/proliferation pathways dysregulated in diabetes and current therapeutic agents studied to induce ß-cell proliferation. Furthermore, we discuss possible combination therapies of proliferation agents with immunosuppressants and antioxidative therapy to improve overall long-term outcomes of diabetes.

11.
Front Mol Neurosci ; 14: 806376, 2021.
Article in English | MEDLINE | ID: mdl-35110996

ABSTRACT

In the mammalian brain, information processing in sensory modalities and global mechanisms of multisensory integration facilitate perception. Emerging experimental evidence suggests that the contribution of multisensory integration to sensory perception is far more complex than previously expected. Here we revise how associative areas such as the prefrontal cortex, which receive and integrate inputs from diverse sensory modalities, can affect information processing in unisensory systems via processes of down-stream signaling. We focus our attention on the influence of the medial prefrontal cortex on the processing of information in the visual system and whether this phenomenon can be clinically used to treat higher-order visual dysfunctions. We propose that non-invasive and multisensory stimulation strategies such as environmental enrichment and/or attention-related tasks could be of clinical relevance to fight cerebral visual impairment.

12.
Biomolecules ; 11(3)2021 03 04.
Article in English | MEDLINE | ID: mdl-33806609

ABSTRACT

BACKGROUND: Biomarkers are crucial for detecting early type-1 diabetes (T1D) and preventing significant ß-cell loss before the onset of clinical symptoms. Here, we present proof-of-concept studies to demonstrate the potential for identifying integrated biomarker signature(s) of T1D using parallel multi-omics. METHODS: Blood from human subjects at high risk for T1D (and healthy controls; n = 4 + 4) was subjected to parallel unlabeled proteomics, metabolomics, lipidomics, and transcriptomics. The integrated dataset was analyzed using Ingenuity Pathway Analysis (IPA) software for disturbances in the at-risk subjects compared to controls. RESULTS: The final quadra-omics dataset contained 2292 proteins, 328 miRNAs, 75 metabolites, and 41 lipids that were detected in all samples without exception. Disease/function enrichment analyses consistently indicated increased activation, proliferation, and migration of CD4 T-lymphocytes and macrophages. Integrated molecular network predictions highlighted central involvement and activation of NF-κB, TGF-ß, VEGF, arachidonic acid, and arginase, and inhibition of miRNA Let-7a-5p. IPA-predicted candidate biomarkers were used to construct a putative integrated signature containing several miRNAs and metabolite/lipid features in the at-risk subjects. CONCLUSIONS: Preliminary parallel quadra-omics provided a comprehensive picture of disturbances in high-risk T1D subjects and highlighted the potential for identifying associated integrated biomarker signatures. With further development and validation in larger cohorts, parallel multi-omics could ultimately facilitate the classification of T1D progressors from non-progressors.


Subject(s)
Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/metabolism , MicroRNAs/metabolism , Biomarkers/metabolism , Genomics , Humans , Metabolomics , MicroRNAs/genetics , Proteomics , Software
13.
PLoS One ; 15(11): e0241925, 2020.
Article in English | MEDLINE | ID: mdl-33152016

ABSTRACT

The application of artificial intelligence (AI) and machine learning (ML) in biomedical research promises to unlock new information from the vast amounts of data being generated through the delivery of healthcare and the expanding high-throughput research applications. Such information can aid medical diagnoses and reveal various unique patterns of biochemical and immune features that can serve as early disease biomarkers. In this report, we demonstrate the feasibility of using an AI/ML approach in a relatively small dataset to discriminate among three categories of samples obtained from mice that either rejected or tolerated their pancreatic islet allografts following transplant in the anterior chamber of the eye, and from naïve controls. We created a locked software based on a support vector machine (SVM) technique for pattern recognition in electropherograms (EPGs) generated by micellar electrokinetic chromatography and laser induced fluorescence detection (MEKC-LIFD). Predictions were made based only on the aligned EPGs obtained in microliter-size aqueous humor samples representative of the immediate local microenvironment of the islet allografts. The analysis identified discriminative peaks in the EPGs of the three sample categories. Our classifier software was tested with targeted and untargeted peaks. Working with the patterns of untargeted peaks (i.e., based on the whole pattern of EPGs), it was able to achieve a 21 out of 22 positive classification score with a corresponding 95.45% prediction accuracy among the three sample categories, and 100% accuracy between the rejecting and tolerant recipients. These findings demonstrate the feasibility of AI/ML approaches to classify small numbers of samples and they warrant further studies to identify the analytes/biochemicals corresponding to discriminative features as potential biomarkers of islet allograft immune rejection and tolerance.


Subject(s)
Forecasting/methods , Graft Rejection/physiopathology , Islets of Langerhans Transplantation/methods , Animals , Artificial Intelligence , Diabetes Mellitus, Experimental/immunology , Female , Graft Survival/immunology , Immune Tolerance , Immunosuppression Therapy/methods , Islets of Langerhans/immunology , Islets of Langerhans/metabolism , Isoantigens/immunology , Machine Learning , Male , Mice , Mice, Inbred C57BL , Mice, Inbred DBA , Support Vector Machine , Transplantation, Homologous
14.
J Proteomics ; 223: 103826, 2020 07 15.
Article in English | MEDLINE | ID: mdl-32442648

ABSTRACT

The applicability and benefits of pancreatic islet transplantation are limited due to various issues including the need to avoid immune-mediated rejection. Here, we used our experimental platform of allogeneic islet transplant in the anterior chamber of the eye (ACE-platform) to longitudinally monitor the progress of rejection in mice and obtain aqueous humor samples representative of the microenvironment of the graft for accurately-timed proteomic analyses. LC-MS/MS-based proteomics performed on such mass-limited samples (~5 µL) identified a total of 1296 proteins. Various analyses revealed distinct protein patterns associated with the mounting of the inflammatory and immune responses and their evolution with the progression of the rejection. Pathway analyses indicated predominant changes in cytotoxic functions, cell movement, and innate and adaptive immune responses. Network prediction analyses revealed transition from humoral to cellular immune response and exacerbation of pro-inflammatory signaling. One of the proteins identified by this localized proteomics as a candidate biomarker of islet rejection, Cystatin 3, was further validated by ELISA in the aqueous humor. This study provides (1) experimental evidence demonstrating the feasibility of longitudinal localized proteomics using small aqueous humor samples and (2) proof-of-concept for the discovery of biomarkers of impending immune attack from the immediate local microenvironment of ACE-transplanted islets. SIGNIFICANCE: The combination of the ACE-platform and longitudinal localized proteomics offers a powerful approach to biomarker discovery during the various stages of immune reactions mounted against transplanted tissues including pancreatic islets. It also supports proteomics-assisted drug discovery and development efforts aimed at preventing rejection through efficacy assessment of new agents by noninvasive and longitudinal graft monitoring.


Subject(s)
Islets of Langerhans Transplantation , Proteomics , Allografts , Animals , Chromatography, Liquid , Graft Rejection , Mice , Tandem Mass Spectrometry
15.
Metabolites ; 9(10)2019 Sep 29.
Article in English | MEDLINE | ID: mdl-31569489

ABSTRACT

(1) Background: Disruption of insulin production by native or transplanted pancreatic islets caused by auto/allo-immunity leads to hyperglycemia, a serious health condition and important therapeutic challenge due to the lifelong need for exogeneous insulin administration. Early metabolic biomarkers can prompt timely interventions to preserve islet function, but reliable biomarkers are currently lacking. We explored the feasibility of "localized metabolomics" where initial biomarker discovery is made in aqueous humor samples for further validation in the circulation. (2) Methods: We conducted non-targeted metabolomic studies in parallel aqueous humor and plasma samples from diabetic and nondiabetic mice. Metabolite levels and associated pathways were compared in both compartments as well as to an earlier longitudinal dataset in hyperglycemia-progressor versus non-progressor non-obese diabetic (NOD) mice. (3) Results: We confirmed that aqueous humor samples can be used to assess metabolite levels. About half of the identified metabolites had well-correlated levels in the aqueous humor and plasma. Several plasma metabolites were significantly different between diabetic and nondiabetic animals and between males and females, and many of them were correlated with the aqueous humor. (4) Conclusions: This study provides proof-of-concept evidence that aqueous humor samples enriched with islet-related metabolites and representative of the immediate islet microenvironment following intraocular islet transplant can be used to assess metabolic changes that could otherwise be overlooked in the general circulation. The findings support localized metabolomics, with and without intraocular islet transplant, to identify biomarkers associated with diabetes and islet allograft rejection.

16.
Article in English | MEDLINE | ID: mdl-29450408

ABSTRACT

Metabolism of the amino acid L-arginine is implicated in many physiological and pathophysiological processes including autoimmune conditions such as type 1 diabetes (T1D). Alternate arginine metabolism through the citrulline-nitric oxide (NO) or the ornithine pathways can lead to proinflammatory or immune regulatory effects, respectively. In this report, we blocked the arginine-ornithine metabolic pathway by inhibiting the enzyme arginase-1 with Nω-hydroxy-nor-arginine (nor-NOHA) to make arginine more available to the alternate citrulline pathway for augmented NO production and increased incidence of autoimmune T1D in female non-obese diabetic (NOD) mice. Unexpectedly, mice receiving nor-NOHA did not develop diabetes although increased NO production is proinflammatory and expected to increase diabetes incidence. These results warrant further studies of the mechanism of action of nor-NOHA, and highlight its potential as a therapeutic agent for the treatment or prevention of T1D.

17.
Food Sci Nutr ; 6(4): 1138-1145, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29983978

ABSTRACT

Iron and zinc deficiencies are global health problems, affecting mostly pregnant women and young children. In 2016, biofortified iron and zinc beans were introduced in Colombia. The incorporation of biofortified beans into the national school-feeding program could facilitate adoption and potentially improve the nutritional status of large populations. However, biofortified beans have to be accepted in order to be consumed by populations. We therefore studied the sensory acceptability of two biofortified beans, BIO-101 and BIO-107, and local beans at schools with free feeding services in two departments of southwest Colombia. Measured on a five-point Likert scale, the mean overall scores were 3.88 ± 0.64, 3.79 ± 0.74, and 3.81 ± 0.76, for BIO-101, BIO-107, and the local bean varieties, respectively, without significant differences. The children in Piendamó (Cauca) slightly preferred BIO-107 over the local bean (p < .05) based on color, smell, and taste. The children in Caicedonia (Valle del Cauca) slightly favored the local bean over BIO-107 (p < .05), regarding size, smell, and taste. Overall acceptability in schoolchildren was good for all beans without significant differences. This study advocates incorporation of accepted biofortified beans in the school-feeding program, in order to reach large groups of schoolchildren and potentially improve their nutritional statuses.

18.
Behav Brain Res ; 321: 137-147, 2017 03 15.
Article in English | MEDLINE | ID: mdl-28062256

ABSTRACT

Aging increases the vulnerability to stress and risk of developing depression. These changes have been related to a reduction of dehydroepiandrosterone (DHEA) levels, an adrenal steroid with anti-stress effects. Also, adult hippocampal neurogenesis decreases during aging and its alteration or impaired is related to the development of depression. Besides, it has been hypothesized that DHEA increases the formation of new neurons. However, it is unknown whether treatment with DHEA in aging may stimulate the dendrite maturation of newborn neurons and reversing depressive-like signs evoked by chronic stress exposure. Here aged male rats (14 months old) were subjected to a scheme of chronic mild stress (CMS) during six weeks, received a treatment with DHEA from the third week of CMS. Changes in body weight and sucrose preference (SP) were measured once a week. DHEA levels were measured in serum, identification of doublecortin-(DCX)-, BrdU- and BrdU/NeuN-labeled cells was done in the dentate gyrus of the hippocampus. CMS produced a gradual reduction in the body weight, but no changes in the SP were observed. Treatment enhanced levels of DHEA, but lack of recovery on body weight of stressed rats. Aging reduced the number of DCX-, BrdU- and BrdU/NeuN- cells but DHEA just significantly increased the number of DCX-cells in rats under CMS and controls, reaching levels of young non-stressed rats (used here as a reference of an optimal status of health). In rats under CMS, DHEA facilitated dendritic maturation of immature new neurons. Our results reveal that DHEA improves neural plasticity even in conditions of CMS in middle age rats. Thus, this hormone reverted the decrement of DCX-cells caused during normal aging.


Subject(s)
Aging/drug effects , Dehydroepiandrosterone/pharmacology , Dendrites/drug effects , Dentate Gyrus/drug effects , Psychotropic Drugs/pharmacology , Stress, Psychological/drug therapy , Aging/physiology , Aging/psychology , Animals , Antigens, Nuclear/metabolism , Body Weight/drug effects , Bromodeoxyuridine , Cell Survival/drug effects , Cell Survival/physiology , Chronic Disease , Dehydroepiandrosterone/blood , Dendrites/metabolism , Dendrites/pathology , Dentate Gyrus/metabolism , Dentate Gyrus/pathology , Dietary Sucrose , Doublecortin Domain Proteins , Doublecortin Protein , Male , Microtubule-Associated Proteins/metabolism , Nerve Tissue Proteins/metabolism , Neurogenesis/drug effects , Neurogenesis/physiology , Neuropeptides/metabolism , Psychotropic Drugs/blood , Random Allocation , Rats, Wistar , Stress, Psychological/metabolism , Stress, Psychological/pathology
19.
MMWR Suppl ; 65(3): 28-34, 2016 Jul 08.
Article in English | MEDLINE | ID: mdl-27389463

ABSTRACT

Establishing a functional incident management system (IMS) is important in the management of public health emergencies. In response to the 2014-2016 Ebola virus disease (Ebola) epidemic in West Africa, CDC established the Emergency Management Development Team (EMDT) to coordinate technical assistance for developing emergency management capacity in Guinea, Liberia, and Sierra Leone. EMDT staff, deployed staff, and partners supported each country to develop response goals and objectives, identify gaps in response capabilities, and determine strategies for coordinating response activities. To monitor key programmatic milestones and assess changes in emergency management and response capacities over time, EMDT implemented three data collection methods in country: coordination calls, weekly written situation reports, and an emergency management dashboard tool. On the basis of the information collected, EMDT observed improvements in emergency management capacity over time in all three countries. The collaborations in each country yielded IMS structures that streamlined response and laid the foundation for long-term emergency management programs.The activities summarized in this report would not have been possible without collaboration with many U.S and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/partners.html).


Subject(s)
Capacity Building/organization & administration , Centers for Disease Control and Prevention, U.S./organization & administration , Epidemics/prevention & control , Hemorrhagic Fever, Ebola/prevention & control , Guinea/epidemiology , Hemorrhagic Fever, Ebola/epidemiology , Humans , International Cooperation , Liberia/epidemiology , Professional Role , Sierra Leone/epidemiology , United States
20.
Gac. méd. Méx ; 157(3): 338-348, may.-jun. 2021. tab
Article in Spanish | LILACS | ID: biblio-1346119

ABSTRACT

Resumen La educación médica ha puesto en práctica diversas estrategias innovadoras con el propósito de alcanzar mejores logros de aprendizaje. Se hace una evaluación de las experiencias relacionadas con el enfoque por competencias, las nuevas tecnologías educativas, las alternativas curriculares, la profesionalización de la evaluación y las técnicas educativas a distancia, para ubicarlas en el lugar que les corresponde.


Abstract Medical education has implemented various innovative strategies with the purpose to attain better learning achievements. An evaluation is made of the experiences in the competencies approach, new learning technologies, curricular alternatives, professional evaluation and distance education technologies in order to locate them in the areas they belong.


Subject(s)
Humans , Education, Distance , Education, Medical , Curriculum , Learning
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