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1.
Adv Sci (Weinh) ; 11(10): e2308507, 2024 Mar.
Article En | MEDLINE | ID: mdl-38145348

Electrode grids are used in neuroscience research and clinical practice to record electrical activity from the surface of the brain. However, existing passive electrocorticography (ECoG) technologies are unable to offer both high spatial resolution and wide cortical coverage, while ensuring a compact acquisition system. The electrode count and density are restricted by the fact that each electrode must be individually wired. This work presents an active micro-electrocorticography (µECoG) implant that tackles this limitation by incorporating metal oxide thin-film transistors (TFTs) into a flexible electrode array, allowing to address multiple electrodes through a single shared readout line. By combining the array with an incremental-ΔΣ readout integrated circuit (ROIC), the system is capable of recording from up to 256 electrodes virtually simultaneously, thanks to the implemented 16:1 time-division multiplexing scheme, offering lower noise levels than existing active µECoG arrays. In vivo validation is demonstrated acutely in mice by recording spontaneous activity and somatosensory evoked potentials over a cortical surface of ≈8×8 mm2 . The proposed neural interface overcomes the wiring bottleneck limiting ECoG arrays, holding promise as a powerful tool for improved mapping of the cerebral cortex and as an enabling technology for future brain-machine interfaces.


Brain Mapping , Cerebral Cortex , Animals , Mice , Electrodes, Implanted , Cerebral Cortex/physiology , Electrocorticography , Electronics
2.
Bol Med Hosp Infant Mex ; 80(Supl 1): 64-68, 2023.
Article En | MEDLINE | ID: mdl-37490685

BACKGROUND: Bowel obstruction due to accidental ingestion of foreign objects occurs rarely in children because 80 to 90% of the objects can pass freely through the gastrointestinal tract. CASE REPORT: We report a case of a 14-month-old infant who presented bowel obstruction caused by the ingestion of hydrogel beads (sodium polyacrylate). Hydrogel beads are used as sensory and didactic toys that can increase their initial size 200 to 400 times by liquid absorption. An abdominal X-ray was perfomed in anteroposterior supine projection, where a round filling defect at the loop of the right flank was detected; this came to our attention because hydrogel beads are usually radiolucent. The diagnosis was established by abdominal ultrasound where free intraperitoneal fluid was reported with data of small bowel pseudo-obstruction by foreign objects. Conservative treatment was prescribed, finding persistence of increased abdominal perimeter, so an enterotomy was performed for their removal; finding impacted hydrogel beads 30 centimeters from the ileocecal valve. CONCLUSIONS: Hydrogel beads are dangerous for the pediatric population. The evolution of the patient was favorable thanks to the knowledge of the foreign objects ingested. The expectant behavior that had to be executed, stands out because we had no knowledge as to the maximum size of the hydrogel in the gastrointestinal tract.


INTRODUCCIÓN: La obstrucción intestinal por ingesta accidental de cuerpos extraños se presenta muy rara vez en la edad pediátrica debido a que del 80 al 90% de los objetos pueden pasar libremente por el tracto gastrointestinal. CASO CLÍNICO: Se aborda el caso de una paciente de sexo femenino de 1 año 2 meses quien presentó obstrucción intestinal debido a la ingesta de esferas de hidrogel (poliacrilato de sodio). Dichas esferas, que son utilizadas como juguetes didácticos o sensoriales, aumentan de 200 a 400 veces su tamaño inicial mediante la absorción de agua. Se realizó radiografía abdominal en proyección decúbito supino, donde llamó la atención el hallazgo de defecto de llenado redondeado en asa de flanco derecho, ya que las esferas de hidrogel son radiolúcidas. El diagnóstico se estableció mediante ultrasonido abdominal, donde se reportó líquido libre peritoneal con datos de suboclusión por cuerpos extraños a nivel intestinal. Se indicó tratamiento conservador, encontrando persistencia de aumento de perímetro abdominal. Se realizó enterotomía y se encontraron las esferas impactadas a 30 centímetros de la válvula ileocecal. CONCLUSIONES: Las esferas de hidrogel son peligrosas para la población pediátrica. La evolución de la paciente fue favorable debido al conocimiento del objeto extraño ingerido. Sobresale la conducta expectante que se tuvo que desempeñar debido a que se desconocía el crecimiento de las esferas y en qué momento no podrían continuar su paso por el tracto gastrointestinal.


Foreign Bodies , Intestinal Obstruction , Infant , Humans , Child , Hydrogels/adverse effects , Intestine, Small , Intestinal Obstruction/etiology , Intestinal Obstruction/surgery , Intestinal Obstruction/diagnosis , Foreign Bodies/complications , Foreign Bodies/diagnosis
3.
Bol. méd. Hosp. Infant. Méx ; 80(supl.1): 64-68, 2023. graf
Article Es | LILACS-Express | LILACS | ID: biblio-1513768

Resumen Introducción: La obstrucción intestinal por ingesta accidental de cuerpos extraños se presenta muy rara vez en la edad pediátrica debido a que del 80 al 90% de los objetos pueden pasar libremente por el tracto gastrointestinal. Caso clínico: Se aborda el caso de una paciente de sexo femenino de 1 año 2 meses quien presentó obstrucción intestinal debido a la ingesta de esferas de hidrogel (poliacrilato de sodio). Dichas esferas, que son utilizadas como juguetes didácticos o sensoriales, aumentan de 200 a 400 veces su tamaño inicial mediante la absorción de agua. Se realizó radiografía abdominal en proyección decúbito supino, donde llamó la atención el hallazgo de defecto de llenado redondeado en asa de flanco derecho, ya que las esferas de hidrogel son radiolúcidas. El diagnóstico se estableció mediante ultrasonido abdominal, donde se reportó líquido libre peritoneal con datos de suboclusión por cuerpos extraños a nivel intestinal. Se indicó tratamiento conservador, encontrando persistencia de aumento de perímetro abdominal. Se realizó enterotomía y se encontraron las esferas impactadas a 30 centímetros de la válvula ileocecal. Conclusiones: Las esferas de hidrogel son peligrosas para la población pediátrica. La evolución de la paciente fue favorable debido al conocimiento del objeto extraño ingerido. Sobresale la conducta expectante que se tuvo que desempeñar debido a que se desconocía el crecimiento de las esferas y en qué momento no podrían continuar su paso por el tracto gastrointestinal.


Abstract Background: Bowel obstruction due to accidental ingestion of foreign objects occurs rarely in children because 80 to 90% of the objects can pass freely through the gastrointestinal tract. Case report: We report a case of a 14-month-old infant who presented bowel obstruction caused by the ingestion of hydrogel beads (sodium polyacrylate). Hydrogel beads are used as sensory and didactic toys that can increase their initial size 200 to 400 times by liquid absorption. An abdominal X-ray was perfomed in anteroposterior supine projection, where a round filling defect at the loop of the right flank was detected; this came to our attention because hydrogel beads are usually radiolucent. The diagnosis was established by abdominal ultrasound where free intraperitoneal fluid was reported with data of small bowel pseudo-obstruction by foreign objects. Conservative treatment was prescribed, finding persistence of increased abdominal perimeter, so an enterotomy was performed for their removal; finding impacted hydrogel beads 30 centimeters from the ileocecal valve. Conclusions: Hydrogel beads are dangerous for the pediatric population. The evolution of the patient was favorable thanks to the knowledge of the foreign objects ingested. The expectant behavior that had to be executed, stands out because we had no knowledge as to the maximum size of the hydrogel in the gastrointestinal tract.

4.
Sci Transl Med ; 14(644): eabg8397, 2022 05 11.
Article En | MEDLINE | ID: mdl-35544594

Despite the hyperproliferative environment marked by activation of ß-catenin and overexpression of c-myc, the epidermis surrounding chronic diabetic foot ulcers (DFUs) is clinically hypertrophic and nonmigratory yet does not undergo malignant transformation. We identified miR193b-3p as a master regulator that contributes to this unique cellular phenotype. We determined that induction of tumor suppressor miR193b-3p is a unique feature of DFUs that is not found in venous leg ulcers, acute wounds, or cutaneous squamous cell carcinoma (SCC). Genomic analyses of DFUs identified suppression of the miR193b-3p target gene network that orchestrates cell motility. Inhibition of migration and wound closure was further confirmed by overexpression of miR193b-3p in human organotypic and murine in vivo wound models, whereas miR193b-3p knockdown accelerated wound reepithelialization in human ex vivo and diabetic murine wounds in vivo. The dominant negative effect of miR193b-3p on keratinocyte migration was maintained in the presence of promigratory miR31-5p and miR15b-5p, which were also overexpressed in DFUs. miR193b-3p mediated antimigratory activity by disrupting stress fiber formation and by decreasing activity of GTPase RhoA. Conversely, miR193b-3p targets that typically participate in malignant transformation were found to be differentially regulated between DFUs and SCC, including the proto-oncogenes KRAS (Kirsten rat sarcoma viral proto-oncogene) and KIT (KIT proto-oncogene). Although miR193b-3p acts as a tumor suppressor contributing to low tumor incidence in DFUs, it also acts as a master inhibitor of cellular migration and epithelialization in DFUs. Thus, miR193b-3p may represent a target for wound healing induction, cancer therapeutics, and diagnostics.


Carcinoma, Squamous Cell , Diabetes Mellitus , Diabetic Foot , Skin Neoplasms , Animals , Cell Movement/genetics , Diabetic Foot/genetics , Diabetic Foot/pathology , Mice , Wound Healing
5.
J Invest Dermatol ; 138(5): 1187-1196, 2018 05.
Article En | MEDLINE | ID: mdl-29273315

Diabetic foot ulcers (DFUs) are a debilitating complication of diabetes in which bacterial presence, including the frequent colonizer Staphylococcus aureus, contributes to inhibition of healing. MicroRNAs (miRs) play a role in healing and host response to bacterial pathogens. However, the mechanisms by which miR response to cutaneous S. aureus contributes to DFU pathophysiology are unknown. Here, we show that S. aureus inhibits wound closure and induces miR-15b-5p in acute human and porcine wound models and in chronic DFUs. Transcriptome analyses of DFU tissue showed induction of miR-15b-5p to be critical, regulating many cellular processes, including DNA repair and inflammatory response, by suppressing downstream targets IKBKB, WEE1, FGF2, RAD50, MSH2, and KIT. Using a human wound model, we confirmed that S. aureus-triggered miR-15b-5p induction results in suppression of the inflammatory- and DNA repair-related genes IKBKB and WEE1. Inhibition of DNA repair and accumulation of DNA breaks was functionally confirmed by the presence of the pH2AX within colonized DFUs. We conclude that S. aureus induces miR-15b-5p, subsequently repressing DNA repair and inflammatory response, showing a mechanism of inhibition of healing in DFUs previously unreported, to our knowledge. This underscores a previously unknown role of DNA damage repair in the pathophysiology of DFUs colonized with S. aureus.


DNA Repair , Diabetic Foot/microbiology , Inflammation/etiology , MicroRNAs/physiology , Staphylococcus aureus/pathogenicity , Animals , Cell Cycle Proteins/genetics , Cells, Cultured , Humans , I-kappa B Kinase/genetics , Nuclear Proteins/genetics , Protein-Tyrosine Kinases/genetics , Swine , Transcriptome
6.
Sci Transl Med ; 9(371)2017 01 04.
Article En | MEDLINE | ID: mdl-28053158

Chronic nonhealing venous leg ulcers (VLUs) are widespread and debilitating, with high morbidity and associated costs; about $15 billion is spent annually on the care of VLUs in the United States. Despite this, there is a paucity of treatments for VLUs because of the lack of pathophysiologic insight into ulcer development as well as the lack of knowledge regarding biologic actions of existing VLU-targeted therapies. The bioengineered bilayered living cellular construct (BLCC) skin substitute is a U.S. Food and Drug Administration-approved biologic treatment for healing VLUs. To elucidate the mechanisms through which the BLCC promotes healing of chronic VLUs, we conducted a clinical trial (NCT01327937) in which patients with nonhealing VLUs were treated with either standard of care (compression therapy) or the BLCC together with standard of care. Tissue was collected from the VLU edge before and 1 week after treatment, and the samples underwent comprehensive microarray mRNA and protein analyses. Ulcers treated with the BLCC skin substitute displayed three distinct transcriptomic patterns, suggesting that BLCC induced a shift from a nonhealing to a healing tissue response, involving modulation of inflammatory and growth factor signaling, keratinocyte activation, and attenuation of Wnt/ß-catenin signaling. In these ways, BLCC application orchestrated a shift from the chronic nonhealing ulcer microenvironment to a distinctive healing milieu resembling that of an acute, healing wound. Our findings provide in vivo evidence in VLU patients of pathways that can be targeted in the design of new therapies to promote healing of chronic VLUs.


Biomedical Engineering/methods , Leg Ulcer/therapy , Skin, Artificial , Varicose Ulcer/therapy , Wound Healing , Adult , Aged , Biocompatible Materials , Biopsy , Collagen/therapeutic use , Cross-Over Studies , Female , Gene Expression Profiling , Humans , Middle Aged , Oligonucleotide Array Sequence Analysis , Phenotype , Skin/metabolism , Treatment Outcome , Young Adult , beta Catenin/metabolism
7.
J Invest Dermatol ; 137(5): 1144-1154, 2017 05.
Article En | MEDLINE | ID: mdl-28017831

Glucocorticoids (GCs), key mediators of stress signals, are also potent wound healing inhibitors. To understand how stress signals inhibit wound healing, we investigated the role of membranous glucocorticoid receptor (mbGR) by using cell-impermeable BSA-conjugated dexamethasone. We found that mbGR inhibits keratinocyte migration and wound closure by activating a Wnt-like phospholipase (PLC)/ protein kinase C (PKC) signaling cascade. Rapid activation of mbGR/PLC/PKC further leads to activation of known biomarkers of nonhealing found in patients, ß-catenin and c-myc. Conversely, a selective inhibitor of PKC, calphostin C, blocks mbGR/PKC pathway, and rescues GC-mediated inhibition of keratinocyte migration in vitro and accelerates wound epithelialization of human wounds ex vivo. This novel signaling mechanism may have a major impact on understanding how stress response via GC signaling regulates homeostasis and its role in development and treatments of skin diseases, including wound healing. To test tissue specificity of this nongenomic signaling mechanism, we tested retinal and bronchial human epithelial cells and fibroblasts. We found that mbGR/PLC/PKC signaling cascade exists in all cell types tested, suggesting a more general role. The discovery of this nongenomic signaling pathway, in which glucocorticoids activate Wnt pathway via mbGR, provides new insights into how stress-mediated signals may activate growth signals in various epithelial and mesenchymal tissues.


Epithelial Cells/metabolism , Glucocorticoids/metabolism , Receptors, Glucocorticoid/metabolism , Signal Transduction , Wound Healing/physiology , Cell Line , Cell Movement/physiology , Cells, Cultured , Fibroblasts/metabolism , Glycogen Synthase Kinase 3 beta/metabolism , Humans , Keratinocytes/metabolism , Protein Kinase C/metabolism , Stress, Physiological/physiology , Type C Phospholipases/metabolism , Wnt Signaling Pathway/physiology , beta Catenin/metabolism
8.
Arch Dermatol Res ; 309(2): 133-139, 2017 Mar.
Article En | MEDLINE | ID: mdl-28013372

Cutaneous squamous cell carcinoma (cSCC) is a malignant proliferation of keratinocytes with an uncertain molecular basis causing significant morbidity. MicroRNAs (miRs) are small RNA molecules that regulate gene expression on post- transcriptional level. MiRs are critical to various biological processes. To determine if miRs play a role in pathogenesis of invasive cSCC, we collected patients' specimens from in situ and invasive cSCC (n = 19) and examined miRs expression levels using qPCR. Specifically, we evaluated miR-21, miR-103a, miR-186, miR-200b, miR-203, and miR-205 expression levels due to their role in skin biology and epithelial to mesenchymal transition. MiR levels were compared between in situ and invasive cSCCs. We found statistically significant (p ≤ 0.05) upregulation of miR-21 and miR-205 in invasive cSCC compared to cSCC in situ. We concluded that miR-21 and miR-205 may have diagnostic value in determining the invasive properties of cSCCs and that each cSCC displays unique miR profile, underscoring the possibility of personalized medicine approach in developing potential novel, less invasive treatments.


Carcinoma, Squamous Cell/genetics , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Skin Neoplasms/genetics , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/pathology , Cell Movement/genetics , Cell Proliferation/genetics , Humans , Keratinocytes/metabolism , MicroRNAs/biosynthesis , Middle Aged , Skin Neoplasms/pathology
9.
Wound Repair Regen ; 24(6): 943-953, 2016 11.
Article En | MEDLINE | ID: mdl-27607190

Diabetic foot ulcers (DFUs) are one of the major complications of diabetes. Its molecular pathology remains poorly understood, impeding the development of effective treatments. Although it has been established that multiple cell types, including fibroblasts, keratinocytes, macrophages, and endothelial cells, all contribute to inhibition of healing, less is known regarding contributions of individual cell type. Thus, we generated primary fibroblasts from nonhealing DFUs and evaluated their cellular and molecular properties in comparison to nondiabetic foot fibroblasts (NFFs). Specifically, we analyzed both micro-RNA and mRNA expression profiles of primary DFU fibroblasts. Paired genomic analyses identified a total of 331 reciprocal miRNA-mRNA pairs including 21 miRNAs (FC > 2.0) along with 239 predicted target genes (FC > 1.5) that are significantly and differentially expressed. Of these, we focused on three miRNAs (miR-21-5p, miR-34a-5p, miR-145-5p) that were induced in DFU fibroblasts as most differentially regulated. The involvement of these microRNAs in wound healing was investigated by testing the expression of their downstream targets as well as by quantifying cellular behaviors in prospectively collected and generated cell lines from 15 patients (seven DFUF and eight NFF samples). We found large number of downstream targets of miR-21-5p, miR-34a-5p, miR-145-5p to be coordinately regulated in mRNA profiles, which was confirmed by quantitative real-time PCR. Pathway analysis on paired miRNA-mRNA profiles predicted inhibition of cell movement and cell proliferation, as well as activation of cell differentiation and senescence in DFU fibroblasts, which was confirmed by cellular assays. We concluded that induction of miR-21-5p, miR-34a-5p, miR-145-5p in DFU dermal fibroblasts plays an important role in impairing multiple cellular functions, thus contributing to overall inhibition of healing in DFUs.


Diabetic Foot/genetics , Diabetic Foot/pathology , Fibroblasts/metabolism , Fibroblasts/pathology , Gene Expression Profiling , MicroRNAs/metabolism , RNA, Messenger/metabolism , Wound Healing , Blotting, Western , Cell Differentiation , Cellular Senescence , Gene Expression Regulation , Humans , Immunohistochemistry , Microarray Analysis , Signal Transduction
10.
PLoS One ; 10(8): e0137133, 2015.
Article En | MEDLINE | ID: mdl-26318001

Diabetes Mellitus (DM) is a chronic, severe disease rapidly increasing in incidence and prevalence and is associated with numerous complications. Patients with DM are at high risk of developing diabetic foot ulcers (DFU) that often lead to lower limb amputations, long term disability, and a shortened lifespan. Despite this, the effects of DM on human foot skin biology are largely unknown. Thus, the focus of this study was to determine whether DM changes foot skin biology predisposing it for healing impairment and development of DFU. Foot skin samples were collected from 20 patients receiving corrective foot surgery and, using a combination of multiple molecular and cellular approaches, we performed comparative analyses of non-ulcerated non-neuropathic diabetic foot skin (DFS) and healthy non-diabetic foot skin (NFS). MicroRNA (miR) profiling of laser captured epidermis and primary dermal fibroblasts from both DFS and NFS samples identified 5 miRs de-regulated in the epidermis of DFS though none reached statistical significance. MiR-31-5p and miR-31-3p were most profoundly induced. Although none were significantly regulated in diabetic fibroblasts, miR-29c-3p showed a trend of up-regulation, which was confirmed by qPCR in a prospective set of 20 skin samples. Gene expression profiling of full thickness biopsies identified 36 de-regulated genes in DFS (>2 fold-change, unadjusted p-value ≤ 0.05). Of this group, three out of seven tested genes were confirmed by qPCR: SERPINB3 was up-regulated whereas OR2A4 and LGR5 were down-regulated in DFS. However no morphological differences in histology, collagen deposition, and number of blood vessels or lymphocytes were found. No difference in proliferative capacity was observed by quantification of Ki67 positive cells in epidermis. These findings suggest DM causes only subtle changes to foot skin. Since morphology, mRNA and miR levels were not affected in a major way, additional factors, such as neuropathy, vascular complications, or duration of DM, may further compromise tissue's healing ability leading to development of DFUs.


Dermis/pathology , Diabetic Foot/genetics , Diabetic Foot/pathology , Epidermis/pathology , Genomics , MicroRNAs/genetics , Fibroblasts/metabolism , Foot Ulcer/genetics , Foot Ulcer/pathology , Gene Expression Profiling , Humans , Transcription, Genetic
11.
Adv Wound Care (New Rochelle) ; 3(7): 445-464, 2014 Jul 01.
Article En | MEDLINE | ID: mdl-25032064

Significance: Keratinocytes, a major cellular component of the epidermis, are responsible for restoring the epidermis after injury through a process termed epithelialization. This review will focus on the pivotal role of keratinocytes in epithelialization, including cellular processes and mechanisms of their regulation during re-epithelialization, and their cross talk with other cell types participating in wound healing. Recent Advances: Discoveries in epidermal stem cells, keratinocyte immune function, and the role of the epidermis as an independent neuroendocrine organ will be reviewed. Novel mechanisms of gene expression regulation important for re-epithelialization, including microRNAs and histone modifications, will also be discussed. Critical Issues: Epithelialization is an essential component of wound healing used as a defining parameter of a successful wound closure. A wound cannot be considered healed in the absence of re-epithelialization. The epithelialization process is impaired in all types of chronic wounds. Future Directions: A comprehensive understanding of the epithelialization process will ultimately lead to the development of novel therapeutic approaches to promote wound closure.

12.
Adv Wound Care (New Rochelle) ; 3(7): 482-491, 2014 Jul 01.
Article En | MEDLINE | ID: mdl-25032068

Significance: Transforming growth factor ß (TGFß) has a crucial role in maintaining skin homeostasis. TGFß signaling is important for re-epithelialization, inflammation, angiogenesis, and granulation tissue formation during wound healing. This review will discuss the most important findings regarding the role of TGFß in epidermal maintenance and its restoration after injury. Recent Advances: Latest findings on the role of TGFß signaling in normal and impaired wound healing, including the role of TGFß pathway in tissue regeneration observed in super-healer animal models, will be reviewed. Critical Issues: The TGFß pathway is attenuated in nonhealing wounds. Observed suppression of TGFß signaling in chronic ulcers may contribute to the loss of tissue homeostasis and the inability of keratinocytes to migrate and close a wound. Future Directions: A better understanding of TGFß signaling may provide new insights not only in the normal epithelialization process, but also in tissue regeneration. Future studies focused on TGFß-mediated crosstalk between multiple cell types involved in wound healing may lead to development of novel therapeutic advances for chronic wounds.

13.
Am J Respir Cell Mol Biol ; 48(5): 665-73, 2013 May.
Article En | MEDLINE | ID: mdl-23371060

Adenosine concentrations are elevated in the lungs of patients with asthma and chronic obstructive pulmonary disease, where it balances between tissue repair and excessive airway remodeling. We previously demonstrated that the activation of the adenosine A2A receptor promotes epithelial wound closure. However, the mechanism by which adenosine-mediated wound healing occurs after cigarette smoke exposure has not been investigated. The present study investigates whether cigarette smoke exposure alters adenosine-mediated reparative properties via its ability to induce a shift in the oxidant/antioxidant balance. Using an in vitro wounding model, bronchial epithelial cells were exposed to 5% cigarette smoke extract, were wounded, and were then stimulated with either 10 µM adenosine or the specific A2A receptor agonist, 5'-(N-cyclopropyl)-carboxamido-adenosine (CPCA; 10 µM), and assessed for wound closure. In a subset of experiments, bronchial epithelial cells were infected with adenovirus vectors encoding human superoxide dismutase and/or catalase or control vector. In the presence of 5% smoke extract, significant delay was evident in both adenosine-mediated and CPCA-mediated wound closure. However, cells pretreated with N-acetylcysteine (NAC), a nonspecific antioxidant, reversed smoke extract-mediated inhibition. We found that cells overexpressing mitochondrial catalase repealed the smoke extract inhibition of CPCA-stimulated wound closure, whereas superoxide dismutase overexpression exerted no effect. Kinase experiments revealed that smoke extract significantly reduced the A2A-mediated activation of cyclic adenosine monophosphate-dependent protein kinase. However, pretreatment with NAC reversed this effect. In conclusion, our data suggest that cigarette smoke exposure impairs A2A-stimulated wound repair via a reactive oxygen species-dependent mechanism, thereby providing a better understanding of adenosine signaling that may direct the development of pharmacological tools for the treatment of chronic inflammatory lung disorders.


Adenosine/physiology , Epithelial Cells/metabolism , Hydrogen Peroxide/metabolism , Smoke , Wound Healing , Acetylcysteine/pharmacology , Adenosine/metabolism , Animals , Bronchi/pathology , Catalase/physiology , Cattle , Cells, Cultured , Cyclic AMP/metabolism , Cyclic AMP-Dependent Protein Kinases/metabolism , Enzyme Activation , Epithelial Cells/drug effects , Free Radical Scavengers/pharmacology , Gene Expression/drug effects , Glutathione/metabolism , Humans , Primary Cell Culture , Protein Kinase C/metabolism , Reactive Oxygen Species/metabolism , Receptor, Adenosine A2A/genetics , Receptor, Adenosine A2A/metabolism , Second Messenger Systems , Nicotiana/chemistry
14.
Cir Cir ; 79(6): 511-9, 2011.
Article En, Es | MEDLINE | ID: mdl-22169368

BACKGROUND: Gastroesophageal reflux occurs frequently in newborns. A relationship has been suspected between reflux and apnea of prematurity. The objective of this study is to determine this relationship, owing to the fact that premature newborns have immaturity of structures, especially esophageal smooth muscle. METHODS: We conducted a longitudinal, analytical, comparative, and observational case/control study. The study was carried out at the Neonatal Intensive Care Unit and in the Gastrointestinal Physiology Department of the Hospital Español (Mexico City) between January 2002 and December 2004. RESULTS: We included 22 patients: 11 females and 11 males. Mean age was 17.8 ± 8.4 days. Premature newborns represented 72.72% (n = 16). Mean gestational age was 33.1 ± 4.18 weeks. All cases were suspicious for central apnea except for three patients with a mixed cause of apnea. All were submitted to a 24-h pHmetry and a simultaneous polysomnography. Polysomnography was positive in 59% (n = 13) and pHmetry was positive in 50% (n = 11). Prematurity had a strong positive relation with central apnea of the newborn (odds ratio: 15 (p = 0.0154)). Odds ratio for association of central apnea and gastroesophageal reflux was 3.2 (p = 0.2037). CONCLUSIONS: We demonstrate that central apnea in the premature newborn is not a cause of gastroesophageal reflux. However, these patients are more likely to have gastroesophageal reflux in the first days of extrauterine life. It is recommended to exclude pathological gastroesophageal reflux when the newborn presents a clinical scenario compatible with central apnea.


Gastroesophageal Reflux/complications , Infant, Premature, Diseases/physiopathology , Sleep Apnea, Central/complications , Bradycardia/complications , Case-Control Studies , Comorbidity , Esophageal pH Monitoring , Female , Follow-Up Studies , Gastroesophageal Reflux/epidemiology , Gastroesophageal Reflux/physiopathology , Gastroesophageal Reflux/therapy , Gestational Age , Humans , Infant, Newborn , Infant, Premature , Infant, Premature, Diseases/etiology , Male , Mexico , Polysomnography , Prognosis , Sleep Apnea, Central/epidemiology , Sleep Apnea, Central/physiopathology , Sleep Apnea, Obstructive/complications
15.
Surg Technol Int ; 21: 51-60, 2011 Dec.
Article En | MEDLINE | ID: mdl-22504970

Chronic wounds represent a significant burden to patients, health care professionals, and the health care system. Micro-RNAs (miRNAs) have recently emerged as a novel class of gene expression modulators involved in regulation of multiple biological processes, including development, differentiation, organogenesis, inflammation, cell proliferation, growth control, and apoptosis. Importantly, aberrant expression or activity of miRNAs can lead to a disease state. However, the role of miRNAs in chronic wounds remains to be elucidated. This article reviews available literature on the role of miRNAs in a range of processes important for successful wound healing including epidermal differentiation and proliferation, inflammation and angiogenesis. The potential role of miRNAs in normal wound healing and their contribution to chronic wound pathology has been anticipated. The prospective use of miRNAs as markers for surgical debridement, and as novel diagnostic and therapeutic targets for chronic wounds is also discussed.

16.
Cir Cir ; 77(5): 397-401, 2009.
Article En | MEDLINE | ID: mdl-19944030

BACKGROUND: Neuroblastoma is a common malignancy in infancy but extremely rare in adults. These tumors, commonly found in the abdomen, originate in the sympathetic nervous system. Staging and management are standardized in children and adults, although their prognosis is very different, being more aggressive and with a poorer outcome in the adult. CLINICAL CASE: We present the case of a 31-year-old male with non-specific abdominal pain and constipation. After several studies, a stage III giant retroperitoneal neuroblastoma was diagnosed. We discuss here the evaluation, management and follow-up of the patient. A literature review is presented as well. CONCLUSIONS: Adult neuroblastoma is an unusual disease with an insidious presentation and is usually diagnosed in advanced stages. Unlike its behavior in young patients, in the adult it is more aggressive and with a poor prognosis.


Neuroblastoma/diagnosis , Retroperitoneal Neoplasms/diagnosis , Abdominal Pain/etiology , Adult , Age of Onset , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Combined Modality Therapy , Constipation/etiology , Humans , Imaging, Three-Dimensional , Male , Neoplasm Staging , Neuroblastoma/complications , Neuroblastoma/diagnostic imaging , Neuroblastoma/drug therapy , Neuroblastoma/pathology , Neuroblastoma/surgery , Prognosis , Remission Induction , Retroperitoneal Neoplasms/complications , Retroperitoneal Neoplasms/diagnostic imaging , Retroperitoneal Neoplasms/drug therapy , Retroperitoneal Neoplasms/pathology , Retroperitoneal Neoplasms/surgery , Severity of Illness Index , Tomography, X-Ray Computed
17.
Cir. & cir ; 77(5): 397-401, sept.-oct. 2009. ilus, tab
Article Es | LILACS | ID: lil-566467

Introducción: El neuroblastoma es una neoplasia común en la infancia, pero extremadamente rara en el adulto. Se origina del sistema nervioso simpático y su localización más común es abdominal. Su estadificación y tratamiento se han estandarizado en niños y adultos, aunque el pronóstico es muy distinto debido a un comportamiento más agresivo y menor sobrevida en los segundos. Caso clínico: Hombre de 31 años de edad evaluado por dolor abdominal inespecífico y constipación, a quien se le diagnosticó gran neuroblastoma retroperitoneal estadio III. Al no tolerar quimioterapia se realizó cirugía. Se presenta la evaluación, manejo y seguimiento, así como una revisión de la literatura. Conclusiones: El neuroblastoma en el adulto es una enfermedad poco común que cursa con una evolución inicial insidiosa y la presentación suele ser en estadios avanzados. A diferencia del comportamiento en la infancia, en el adulto es más agresivo y con menor sobrevida a pesar de realizar el mismo tratamiento.


BACKGROUND: Neuroblastoma is a common malignancy in infancy but extremely rare in adults. These tumors, commonly found in the abdomen, originate in the sympathetic nervous system. Staging and management are standardized in children and adults, although their prognosis is very different, being more aggressive and with a poorer outcome in the adult. CLINICAL CASE: We present the case of a 31-year-old male with non-specific abdominal pain and constipation. After several studies, a stage III giant retroperitoneal neuroblastoma was diagnosed. We discuss here the evaluation, management and follow-up of the patient. A literature review is presented as well. CONCLUSIONS: Adult neuroblastoma is an unusual disease with an insidious presentation and is usually diagnosed in advanced stages. Unlike its behavior in young patients, in the adult it is more aggressive and with a poor prognosis.


Humans , Male , Adult , Retroperitoneal Neoplasms/diagnosis , Neuroblastoma/diagnosis , Age of Onset , Combined Modality Therapy , Constipation/etiology , Abdominal Pain/etiology , Imaging, Three-Dimensional , Neoplasm Staging , Retroperitoneal Neoplasms/drug therapy , Retroperitoneal Neoplasms/pathology , Retroperitoneal Neoplasms , Retroperitoneal Neoplasms/surgery , Neuroblastoma/complications , Neuroblastoma/drug therapy , Neuroblastoma/pathology , Neuroblastoma , Neuroblastoma/surgery , Prognosis , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Remission Induction , Severity of Illness Index , Tomography, X-Ray Computed
18.
16 de abril ; (217)2004. ilus
Article Es | CUMED | ID: cum-33697

Se informó un adulto de 29 años de edad que presentó tos seca sin expectoración, disnea, disfagia a los sólidos, pérdida de peso no cuantificada, masa tumoral paraesternal izquierda visible y dolor en fosas lumbares. En el estudio efectuado se encontró en el Rx de tórax ensanchamiento mediastinal el cual era responsable de toda la sintomatología acompañante. El US y la TAC revelaron la presencia de varias metástasis en el hígado. La biopsia de la tumoración confirmó el diagnóstico. Dicho paciente era portador de un Tumor de Células Germinales (Tumor del Seno Endodérmico). Esta entidad aparece en niños y adolescentes, en contadas ocasiones se han encontrado casos en el adulto(AU)


Mediastinal Neoplasms/diagnosis , Endodermal Sinus Tumor/diagnosis
19.
Rev. argent. cir ; 60(6): 213-5, jun. 1991. ilus
Article Es | BINACIS | ID: bin-26377

El objetivo del siguiente estudio es la presentación de un nuevo método de planimetría computada para evaluar la motilidad esofágica segmentaria durante la deglutación. En un adulto sano se procedió a filmar la peristalsis esofágica durante la deglutación. Los contornos del esófago fueron dibujados y superpuestos durante la proyección de cada cuadro y posteriormente presentados en un gráfico de planimetría computada de tres ejes donde se observan los segmentos esofágicos contrayéndose y relajándose en función del tiempo. La filmación a alta velocidad y la posterior fijación de la imagen posibilitaria la visualización de detalles funcionales y patológicos desconocidos hasta ahora


Esophagus/physiopathology , Esophageal Diseases/diagnosis , Deglutition , Peristalsis , Barium Sulfate/diagnosis
20.
Rev. argent. cir ; 60(6): 213-5, jun. 1991. ilus
Article Es | LILACS | ID: lil-105887

El objetivo del siguiente estudio es la presentación de un nuevo método de planimetría computada para evaluar la motilidad esofágica segmentaria durante la deglutación. En un adulto sano se procedió a filmar la peristalsis esofágica durante la deglutación. Los contornos del esófago fueron dibujados y superpuestos durante la proyección de cada cuadro y posteriormente presentados en un gráfico de planimetría computada de tres ejes donde se observan los segmentos esofágicos contrayéndose y relajándose en función del tiempo. La filmación a alta velocidad y la posterior fijación de la imagen posibilitaria la visualización de detalles funcionales y patológicos desconocidos hasta ahora


Esophagus/physiopathology , Esophageal Diseases/diagnosis , Barium Sulfate , Deglutition , Peristalsis
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