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1.
Mar Drugs ; 20(10)2022 Sep 26.
Article in English | MEDLINE | ID: mdl-36286429

ABSTRACT

(+)-Aeroplysinin-1 (Apl-1) is a brominated compound isolated from the marine sponge Aplysina aerophoba that exhibits pleiotropic bioactive effects, impairing cell growth in cancer cells, inhibiting angiogenesis in vitro and in vivo and modulating the redox status of different cell types, among other reported activities. In addition to the aforementioned effects, the anti-inflammatory potential of this natural compound was explored in previous work of our laboratory, but the mechanism of action underlying this effect was not described. In this work, we delve into the anti-inflammatory effect of Apl-1 in the context of vascular endothelial cells in vitro, providing new data regarding the molecular mechanism underlying this activity. The characterization of the mechanism of action points to an inhibitory effect of Apl-1 on the NF-κB pathway, one of the main axes involved in endothelial response during inflammatory events. Our results show that Apl-1 can inhibit the expression of pro-inflammatory genes in tumor necrosis factor alpha (TNF-α)- and lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs), targeting the nuclear factor kappa B subunit (NF-κB) pathway through a mechanism of action involving the inhibition of I kappa B kinase (IKK) complex phosphorylation and RelA/p65 nuclear import. In addition, Apl-1 prevented the phosphorylation of Akt induced by TNF-α in HUVECs, probably supporting the inhibitory effect of this compound in the NF-κB pathway. Experimental evidence reported in this work opens the door to the potential pharmacological use of this compound as an anti-inflammatory agent in diseases that course with a pathological endothelial response to inflammation, such as atherosclerosis.


Subject(s)
NF-kappa B , Porifera , Animals , Humans , NF-kappa B/metabolism , Tumor Necrosis Factor-alpha/metabolism , I-kappa B Kinase/metabolism , I-kappa B Kinase/pharmacology , Lipopolysaccharides/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Porifera/metabolism , Signal Transduction , Human Umbilical Vein Endothelial Cells , Anti-Inflammatory Agents/pharmacology
2.
Int J Mol Sci ; 23(24)2022 Dec 15.
Article in English | MEDLINE | ID: mdl-36555614

ABSTRACT

The dimethyl derivative of the immunomodulator itaconate has been previously shown to have anti-inflammatory, anti-oxidative, and immunomodulatory effects. In the present work, we evaluate the potential of dimethyl itaconate as an anti-angiogenic compound by using cultured endothelial cells and several in vitro assays that simulate key steps of the angiogenic process, including endothelial cell proliferation, migration, invasion, and tube formation. Our results show that dimethyl itaconate interferes with all the previously mentioned steps of the angiogenic process, suggesting that dimethyl itaconate behaves as an anti-angiogenic compound.


Subject(s)
Cardiovascular Physiological Phenomena , Endothelial Cells , Cells, Cultured , Immunologic Factors/pharmacology , Adjuvants, Immunologic
3.
J Biomed Sci ; 28(1): 14, 2021 Feb 20.
Article in English | MEDLINE | ID: mdl-33610185

ABSTRACT

BACKGROUND: Glutaminase isoenzymes GLS and GLS2 play apparently opposing roles in cancer: GLS acts as an oncoprotein, while GLS2 (GAB isoform) has context specific tumour suppressive activity. Some microRNAs (miRNAs) have been implicated in progression of tumours, including gliomas. The aim was to investigate the effect of GLS and GAB expression on both miRNAs and oxidative status in glioblastoma cells. METHODS: Microarray profiling of miRNA was performed in GLS-silenced LN229 and GAB-transfected T98G human glioblastoma cells and their wild-type counterparts. Results were validated by real-time quantitative RT-PCR. Oxidative status and antioxidant enzymes were determined by spectrophotometric or fluorescence assays in GLS-silenced LN229 and T98G, and GAB-transfected LN229 and T98G. RESULTS: MiRNA-146a-5p, miRNA-140-3p, miRNA-21-5p, miRNA-1260a, and miRNA-92a-3p were downregulated, and miRNA-1246 was upregulated when GLS was knocked down. MiRNA-140-3p, miRNA-1246, miRNA-1260a, miRNA-21-5p, and miRNA-146a-5p were upregulated when GAB was overexpressed. Oxidative status (lipid peroxidation, protein carbonylation, total antioxidant capacity, and glutathione levels), as well as antioxidant enzymes (catalase, superoxide dismutase, and glutathione reductase) of silenced GLS glioblastoma cells and overexpressed GAB glioblastoma cells significantly changed versus their respective control glioblastoma cells. MiRNA-1246, miRNA-1260a, miRNA-146a-5p, and miRNA-21-5p have been characterized as strong biomarkers of glioblastoma proliferation linked to both GLS silencing and GAB overexpression. Total glutathione is a reliable biomarker of glioblastoma oxidative status steadily associated to both GLS silencing and GAB overexpression. CONCLUSIONS: Glutaminase isoenzymes are related to the expression of some miRNAs and may contribute to either tumour progression or suppression through certain miRNA-mediated pathways, proving to be a key tool to switch cancer proliferation and redox status leading to a less malignant phenotype. Accordingly, GLS and GAB expression are especially involved in glutathione-dependent antioxidant defence.


Subject(s)
Gene Expression Regulation, Neoplastic , Glioblastoma/metabolism , Glutaminase/genetics , MicroRNAs/metabolism , Oxidative Stress , Cell Line, Tumor , Down-Regulation , Glutaminase/metabolism , Humans , Isoenzymes/genetics , Isoenzymes/metabolism , Up-Regulation
5.
J Agric Food Chem ; 72(23): 13023-13038, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38809962

ABSTRACT

Extra virgin olive oil (EVOO), a staple of the Mediterranean diet, is rich in phenolic compounds recognized for their potent bioactive effects, including anticancer and anti-inflammatory properties. However, its effects on vascular health remain relatively unexplored. In this study, we examined the impact of a "picual" EVOO extract from Jaén, Spain, on endothelial cells. Proteomic analysis revealed the modulation of angiogenesis-related processes. In subsequent in vitro experiments, the EVOO extract inhibited endothelial cell migration, adhesion, invasion, ECM degradation, and tube formation while inducing apoptosis. These results provide robust evidence of the extract's antiangiogenic potential. Our findings highlight the potential of EVOO extracts in mitigating angiogenesis-related pathologies, such as cancer, macular degeneration, and diabetic retinopathy.


Subject(s)
Angiogenesis Inhibitors , Cell Movement , Olive Oil , Plant Extracts , Proteomics , Olive Oil/chemistry , Humans , Angiogenesis Inhibitors/pharmacology , Angiogenesis Inhibitors/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Cell Movement/drug effects , Olea/chemistry , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Apoptosis/drug effects , Spain , Human Umbilical Vein Endothelial Cells/metabolism , Human Umbilical Vein Endothelial Cells/drug effects , Cell Adhesion/drug effects
6.
Biomed Pharmacother ; 165: 115234, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37523982

ABSTRACT

Phenolic compounds play a key role in the health benefits of Extra Virgin Olive Oil (EVOO). Among these molecules, the focus has been recently put on (-)-oleocanthal and (-)-oleacein, for which anti-cancer and angiogenesis-related findings have been reported. Here, we explored the modulatory action of (-)-oleocanthal and (-)-oleacein on angiogenesis, the process by which new vessels are created from pre-existent ones, which is directly linked to tumor progression and other pathological conditions. Two in vivo models strongly sustained by angiogenesis, and an in vitro model of endothelial cells to study different steps of angiogenesis, were used. In vivo evidence pointed to the anti-angiogenic effects of both compounds in vivo. In vitro, (-)-oleacein and (-)-oleocanthal inhibited the proliferation, invasion, and tube formation of endothelial cells, and (-)-oleacein significantly repressed migration and induced apoptosis in these cells. Mechanistically, the compounds modulated signaling pathways related to survival and proliferation, all at concentrations of physiological relevance for humans. We propose (-)-oleacein and (-)-oleocanthal as good candidates for angioprevention and for further studies as modulators of angiogenesis in clinical interventions, and as interesting functional claims for the food industry. Chemical compounds studied in this article: Oleocanthal (PubChem CID: 11652416); Oleacein (PubChem CID: 18684078).


Subject(s)
Endothelial Cells , Phenols , Humans , Olive Oil/chemistry , Phenols/pharmacology , Phenols/analysis , Aldehydes/pharmacology
7.
Antioxidants (Basel) ; 12(8)2023 Jul 28.
Article in English | MEDLINE | ID: mdl-37627508

ABSTRACT

Hydroxytyrosol (HT) is a bioactive phenolic compound naturally present in olives and extra virgin olive oil (EVOO) which is described as an antioxidant, antitumoral and antiangiogenic molecule. Previous studies of semi-synthetic HT-derivatives presented the hydroxytyrosyl alkyl ether HT-C6 as one of the most potent derivatives studied in the context of antioxidant, anti-platelet and antiangiogenic assays, but its direct effect on inflammation was not reported. In this work, we use RT-qPCR measure of gene expression, protein analysis by Western-blot and immunofluorescence techniques, adhesion and migration functional assays and single-cell monitoring of reactive oxygen species (ROS) in order to explore in vitro the ability of HT-C6 to interfere in the inflammatory response of endothelial cells (ECs). Our results showed that HT-C6 strongly reduces the TNF-α-induced expression of vascular cell adhesion molecule 1 (VCAM1), intercellular cell adhesion molecule 1 (ICAM1), E-selectin (SELE), C-C motif chemokine ligand 2 and 5 (CCL2 and CCL5) in HUVECs, impairing the chemotactic and adhesion potential of these cells towards THP-1 monocytes in vitro. In this work, we define a mechanism of action underlying the anti-inflammatory effect of HT-C6, which involves the abrogation of nuclear factor kappa B (NF-κB) pathway activation in ECs. These results, together with the ability of HT-C6 to reduce ROS formation in ECs, point to this compound as a promising HT-derivative to be tested in the treatment of atherosclerosis.

8.
Anesth Pain Med ; 12(3): e123829, 2022 Jun.
Article in English | MEDLINE | ID: mdl-36818480

ABSTRACT

Introduction: The incidence of tracheal stenosis is progressively increasing. A risk factor for developing this clinical condition is a history of prolonged endotracheal intubation. A transnasal humidified rapid insufflation ventilatory exchange, known as THRIVE, has gained importance in tracheal resection surgeries. Case Presentation: Herein, we describe the anesthetic management of two obstetric patients, a 19-year-old and 29-year-old, with a history of prolonged endotracheal intubation and a diagnosis of tracheal stenosis. The patients required the resection of the tracheal segment and end-to-end anastomosis. The anesthetic management focused on THRIVE using a high-flow nasal cannula. Conclusions: This system proved to be a safe anesthetic technique for pregnant women and the fetus. Furthermore, it allowed surgeons to better visualize the surgical field without the risk of accidental injury to the endotracheal tube.

9.
Orthop J Sports Med ; 9(1): 2325967120981636, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33614800

ABSTRACT

BACKGROUND: Lateral patellar dislocation can become a recurrent problem after the first episode. Identifying those patients who are at increased risk of redislocation is important for the treatment decision-making process. PURPOSE: To identify clinical and radiologic risk factors for recurrence of patellar dislocation after a first episode. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: The study included patients with lateral patellar dislocation and a 1-year minimum follow-up who were seen between 2011 and 2018. Patients aged 10 to 65 years were included. Patient characteristics, physical examination (patellar apprehension, J sign), and radiographs were reviewed. The Caton-Deschamps and Insall-Salvati ratios were used to evaluate patella alta. High-grade trochlear dysplasia was defined as Dejour types B, C, and D. RESULTS: A total of 130 patients (139 knees) with primary lateral patellar dislocation were included. Recurrent dislocation was seen in 83 knees (59.71%). Stepwise logistic regression analysis demonstrated that Caton-Deschamps ratio ≥1.15 (OR, 2.39; 95% CI, 1.09-5.22; P = .029), age <21 years (OR, 2.53; 95% CI, 1.11-5.77; P = .027), and high-grade trochlear dysplasia (OR, 4.17; 95% CI, 1.90-9.17; P < .001) were significantly associated with patellar redislocation. Based on the presence of these factors, the probability of dislocation after a first lateral patellar dislocation was 31.2% with no factors present, 36.6% with any 1 factor present, 71.7% with any 2 factors present, and 86.2% if all 3 conditions were present. CONCLUSION: The results of this study indicated that patella alta, high-grade trochlear dysplasia, and age <21 years were independent risk factors for patellar redislocation after a first episode, with an additive effect when they were present together. This may help to guide the type of treatment for these patients.

10.
Rev Colomb Obstet Ginecol ; 72(3): 258-270, 2021 09 30.
Article in English, Spanish | MEDLINE | ID: mdl-34851569

ABSTRACT

Objective: To describe the clinical characteristics and the frequency of maternal, fetal and neonatal complications in accordance with the neuraxial anesthesia (NA) technique in women with twin-totwin transfusion syndrome (TTTS) treated with laser photocoagulation. Materials and Methods: Descriptive retrospective cohort study of pregnant patients with TTTS treated with laser photocoagulation under NA at Fundación Valle del Lili, Cali (Colombia), between 2013-2017. Patients with Quintero stage V TTTS were excluded. The protocol was approved by the institutional ethics committee. Results: Of the participants, 32 met the inclusion and exclusion criteria. The study population consisted of young, multiparous women. Urgent interventions were performed in 87.5% of cases; 43.7% were Quintero stage III and epidural anesthesia was used in 56.2% of the women. Maternal hemodynamic variables were similar, in accordance with the timing of surgery and the neuraxial technique used. Sustained hypotension occurred in 65.6% of the pregnant women and 9.3% developed pulmonary edema. Pre-term delivery occurred in 65.6% of the patients and 18.7% had premature rupture of membranes. There were 14 fetal demises and five neonatal deaths. There were no cases of maternal mortality. Conclusions: In patients with TTTS requiring laser photocoagulation, the use of epidural, spinal or combined anesthesia is likely associated with similar maternal hemodynamic variables at the time of surgery. Practitioners providing care to these pregnant women must be aware of the frequent occurrence of maternal, fetal and neonatal complications. Prospective studies to assess the safety and effectiveness of the different neuraxial anesthesia techniques in patients with TTTS are required.


Objetivo: describir las características clínicas y la frecuencia de complicaciones maternas, fetales y neonatales, según técnica de anestesia neuroaxial (AN) en mujeres con síndrome de transfusión feto-fetal (STFF) tratadas con fotocoagulación láser (FL). Materiales y métodos: estudio de cohorte retrospectiva descriptivo. Se incluyeron gestantes con STFF tratadas con FL y AN en la Fundación Valle del Lili, Cali (Colombia) entre 2013-2017. Se excluyeron pacientes con STFF estadio-V de Quintero. Se usó estadística descriptiva. El protocolo fue aprobado por el Comité de Ética de la institución. Resultados: 32 participantes cumplieron con los criterios de inclusión y de exclusión. La población estuvo constituida por mujeres jóvenes, multíparas. En el 87,5% de los casos se realizó intervención de urgencia. El 43,7% presentaba el estadio-III de Quintero y en el 56,2 % de las gestantes se utilizó anestesia epidural. Las variables hemodinámicas maternas exhibieron un comportamiento similar, acorde al momento de la cirugía y la técnica neuoraxial implementada. El 65,6 % de las gestantes presentó hipotensión sostenida y el 9,3 % desarrolló edema pulmonar. El 65,6 % de las pacientes experimentó parto pretérmino y el 18,7 % ruptura prematura de membranas. Se registraron 14 muertes fetales y cinco neonatales. No se registraron casos de mortalidad materna. Conclusiones: en pacientes con STFF que requieren FL, el uso de la anestesia epidural, espinal o combinada probablemente se asocia con un comportamiento similar al de las variables hemodinámicas maternas, durante los momentos de la cirugía. Los profesionales que brindan atención a estas gestantes deben estar alerta ante la frecuente aparición de complicaciones maternas, fetales y neonatales. Se requieren estudios prospectivos que evalúen la seguridad y la efectividad de las diferentes técnicas de anestesia neuroaxial en pacientes con STFF.


Subject(s)
Anesthesia, Epidural , Fetofetal Transfusion , Anesthesia, Epidural/adverse effects , Female , Fetofetal Transfusion/surgery , Fetoscopy/adverse effects , Gestational Age , Humans , Laser Coagulation , Lasers , Pregnancy , Pregnancy, Twin , Prospective Studies , Retrospective Studies
11.
Food Chem ; 333: 127476, 2020 Dec 15.
Article in English | MEDLINE | ID: mdl-32688305

ABSTRACT

The phenolic compound hydroxytyrosol and its derivatives are responsible for some of the health benefits of the intake of virgin olive oil, having shown antiangiogenic properties. In this study, we explored the antiangiogenic potential of six synthetic hydroxytyrosyl alkyl ethers (HT C1, C2, C4, C6, C8 and C12). Our results showed that all compounds affected endothelial cell viability in vitro at low micromolar doses. In addition, compounds HT C1, C2, C4 and C6 inhibited endothelial cell migration and formation of tubular-like structures. In these assays, hydroxytyrosyl hexyl ether (HT C6) exhibited the most potent inhibitory activity in vitro, activating as well apoptosis in endothelial cells. Furthermore, the antiangiogenic activity of HT C6 was confirmed in vivo in the chick chorioallantoic membrane assay. Hence, we present hydroxytyrosol synthetic derivative HT C6 as a new antiangiogenic compound and as a good candidate for an antiangiogenic drug in the treatment of angiogenesis-dependent diseases.


Subject(s)
Angiogenesis Inhibitors/pharmacology , Endothelial Cells/drug effects , Ethers/pharmacology , Phenylethyl Alcohol/analogs & derivatives , Animals , Aorta , Apoptosis , Endothelial Cells/physiology , Ethers/chemistry , Olive Oil/chemistry , Phenols/chemistry , Phenols/pharmacology , Phenylethyl Alcohol/chemistry , Phenylethyl Alcohol/pharmacology
12.
J Clin Orthop Trauma ; 11(Suppl 5): S711-S716, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32999544

ABSTRACT

OBJECTIVE: this study aims to evaluate the relationship between body mass index (BMI), age at which knee joint arthroplasty is performed and complications. The hypothesis is that the higher the BMI, the greater likelihood that the patient will require surgery at an earlier age.Methods: this is a cohort study with all patients who underwent a primary knee arthroplasty, between August 2013 and February 2019, in a tertiary level university hospital. Association between BMI, age and complications were analyzed. Quality of life of patients was also evaluated with the Oxford Knee Score (OKS). RESULTS: 565 primary total knee replacements (TKR) were performed. A cut-off point was found in BMI of 30; 348 patients had a BMI ≤30 and 173 patients had a BMI >30. When comparing the two groups, a statistically significant difference (p = 0.0186) was found in the age at which the TKR was performed. There was a significant improvement for both groups in functional score (Oxford knee score). Additionally, intra and post-operative complications showed no statistically significant difference. CONCLUSION: patients with BMI greater than 30 required primary knee arthroplasty at a younger age (average: 3.5 years), compared to patients with a lower BMI. Obesity does not appear to confer and independent risk for surgery in the short and mid-term. Knee arthroplasty improves significantly quality of life in the short and mid-term, regardless of their BMI, as measured with the OKS.

13.
Arthrosc Tech ; 9(1): e9-e14, 2020 Jan.
Article in English | MEDLINE | ID: mdl-32021767

ABSTRACT

Anterior cruciate ligament (ACL) reconstruction with hamstring tendons has gained popularity in the past and is the most used type of graft in several national registries. It usually involves the harvest of both gracilis and semitendinosus tendons from the ipsilateral knee. More recently, the use of only 1 of the tendons (semitendinosus) in a tripled or quadrupled arrangement has been described, especially in an all-inside type of reconstruction. Having a thicker tendon with a quadrupled semitendinosus (ST), instead of double gracilis and ST enables to a have a graft with enough diameter to resemble more closely the native ACL and decreases the risk of graft rerupture. This Technical Note aims to present a way of reconstructing the ACL using a quadrupled ST graft, with suspensory cortical button in femur and interference screw in tibia, as an alternative to the all-inside technique.

14.
Sci Rep ; 10(1): 2259, 2020 02 10.
Article in English | MEDLINE | ID: mdl-32042057

ABSTRACT

Glutaminase (GA) catalyzes the first step in mitochondrial glutaminolysis playing a key role in cancer metabolic reprogramming. Humans express two types of GA isoforms: GLS and GLS2. GLS isozymes have been consistently related to cell proliferation, but the role of GLS2 in cancer remains poorly understood. GLS2 is repressed in many tumor cells and a better understanding of its function in tumorigenesis may further the development of new therapeutic approaches. We analyzed GLS2 expression in HCC, GBM and neuroblastoma cells, as well as in monkey COS-7 cells. We studied GLS2 expression after induction of differentiation with phorbol ester (PMA) and transduction with the full-length cDNA of GLS2. In parallel, we investigated cell cycle progression and levels of p53, p21 and c-Myc proteins. Using the baculovirus system, human GLS2 protein was overexpressed, purified and analyzed for posttranslational modifications employing a proteomics LC-MS/MS platform. We have demonstrated a dual targeting of GLS2 in human cancer cells. Immunocytochemistry and subcellular fractionation gave consistent results demonstrating nuclear and mitochondrial locations, with the latter being predominant. Nuclear targeting was confirmed in cancer cells overexpressing c-Myc- and GFP-tagged GLS2 proteins. We assessed the subnuclear location finding a widespread distribution of GLS2 in the nucleoplasm without clear overlapping with specific nuclear substructures. GLS2 expression and nuclear accrual notably increased by treatment of SH-SY5Y cells with PMA and it correlated with cell cycle arrest at G2/M, upregulation of tumor suppressor p53 and p21 protein. A similar response was obtained by overexpression of GLS2 in T98G glioma cells, including downregulation of oncogene c-Myc. Furthermore, human GLS2 was identified as being hypusinated by MS analysis, a posttranslational modification which may be relevant for its nuclear targeting and/or function. Our studies provide evidence for a tumor suppressor role of GLS2 in certain types of cancer. The data imply that GLS2 can be regarded as a highly mobile and multilocalizing protein translocated to both mitochondria and nuclei. Upregulation of GLS2 in cancer cells induced an antiproliferative response with cell cycle arrest at the G2/M phase.


Subject(s)
Carcinogenesis/metabolism , Cell Cycle Checkpoints , Cell Differentiation , Glutaminase/physiology , Neoplasms/metabolism , Animals , COS Cells , Cell Line, Tumor , Cell Proliferation , Chlorocebus aethiops , Hep G2 Cells , Humans
15.
J Neuropathol Exp Neurol ; 77(12): 1122-1136, 2018 12 01.
Article in English | MEDLINE | ID: mdl-30364991

ABSTRACT

In congenital hydrocephalus, cerebrospinal fluid accumulation is associated with increased intracranial pressure (ICP), ischemia/hypoxia, metabolic impairment, neuronal damage, and astrocytic reaction. The aim of this study was to identify whether a metabolite profile revealing tissue responses according to the severity of hydrocephalus can be detected. The hyh mutant mouse used for this study exhibits 2 different forms of hydrocephalus, severe and moderate. In a comprehensive investigation into the 2 progressions of hydrocephalus, mice with severe hydrocephalus were found to have higher ICP and astrocytic reaction. Several metabolites from the mouse brain cortex were analyzed with 1H high-resolution magic angle spinning nuclear magnetic resonance (1H HR-MAS NMR) spectroscopy. A differential profile for metabolites including glutamate and glutamine was found to correlate with the severity of hydrocephalus and can be explained due to differential astrocytic reactions, neurodegenerative conditions, and the presence of ischemia. The glutamate transporter EAAT2 and the metabolite taurine were found to be key histopathological markers of affected parenchymata. In conclusion, a differential metabolite profile can be detected according to the severity of hydrocephalus and associated ICP and therefore can be used to monitor the efficacy of experimental therapies.


Subject(s)
Hydrocephalus/genetics , Hydrocephalus/pathology , Metabolome/physiology , Neurodegenerative Diseases/genetics , Neurodegenerative Diseases/pathology , Severity of Illness Index , Animals , Female , Hydrocephalus/metabolism , Male , Mice , Mice, Transgenic , Neurodegenerative Diseases/metabolism
16.
Front Mol Neurosci ; 10: 278, 2017.
Article in English | MEDLINE | ID: mdl-28928633

ABSTRACT

Lysophosphatidic acid (LPA) is an extracellular lipid mediator that regulates nervous system development and functions acting through G protein-coupled receptors (GPCRs). Here we explore the crosstalk between LPA1 receptor and glutamatergic transmission by examining expression of glutaminase (GA) isoforms in different brain areas isolated from wild-type (WT) and KOLPA1 mice. Silencing of LPA1 receptor induced a severe down-regulation of Gls-encoded long glutaminase protein variant (KGA) (glutaminase gene encoding the kidney-type isoforms, GLS) protein expression in several brain regions, particularly in brain cortex and hippocampus. Immunohistochemical assessment of protein levels for the second type of glutaminase (GA) isoform, glutaminase gene encoding the liver-type isoforms (GLS2), did not detect substantial differences with regard to WT animals. The regional mRNA levels of GLS were determined by real time RT-PCR and did not show significant variations, except for prefrontal and motor cortex values which clearly diminished in KO mice. Total GA activity was also significantly reduced in prefrontal and motor cortex, but remained essentially unchanged in the hippocampus and rest of brain regions examined, suggesting activation of genetic compensatory mechanisms and/or post-translational modifications to compensate for KGA protein deficit. Remarkably, Golgi staining of hippocampal regions showed an altered morphology of glutamatergic pyramidal cells dendritic spines towards a less mature filopodia-like phenotype, as compared with WT littermates. This structural change correlated with a strong decrease of active matrix-metalloproteinase (MMP) 9 in cerebral cortex and hippocampus of KOLPA1 mice. Taken together, these results demonstrate that LPA signaling through LPA1 influence expression of the main isoenzyme of glutamate biosynthesis with strong repercussions on dendritic spines maturation, which may partially explain the cognitive and learning defects previously reported for this colony of KOLPA1 mice.

17.
Rev. colomb. ortop. traumatol ; 36(3): 1-6, 2022. tab
Article in Spanish | LILACS, COLNAL | ID: biblio-1532622

ABSTRACT

Introducción: La artroscopia de rodilla es usualmente un procedimiento seguro con pocas complicaciones. El objetivo de este estudio es calcular la incidencia de eventos tromboembólicos sintomáticos: trombosis venosa profunda y tromboembolismo pulmonar, asociados a artroscopia de rodilla y los posibles factores de riesgo relacionados. Materiales and Métodos: Cohorte retrospectiva que incluyó todos los pacientes llevados a artroscopia de rodilla entre Enero 2011 y Diciembre 2015 en un hospital universitario. El seguimiento fue de 30 días después de la cirugía. Se registraron datos demográficos, los eventos de interés, el tipo de cirugía y los posibles factores de riesgo. Resultados: 1,097 artroscopias de rodilla se hicieron en los 5 años. El 100% tuvieron seguimiento de 10 días mínimo, 90.5% alcanzaron el seguimiento de 30 días. El tiempo promedio de seguimiento fue 15.1 meses. El porcentaje de eventos tromboembólicos fue de 1.4% (n = 14). Se encontraron dos factores de riesgo asociados: eventos tromboembólicos previos (p = 0.013) y uso de anticoagulantes previo a la cirugía (p=0.001). La edad promedio fue mayor en los pacientes con eventos tromboembólicos comparado con los que no tuvieron eventos (58 vs 46 años), p = 0.009. Discusión: La incidencia de eventos tromboembólicos sintomáticos tras artroscopia de rodilla es bajo. El uso rutinaio de profilaxis tromboembólica no se recomienda. En los pacientes con historia de eventos tromboembólicos previos o que estpan anticoagulados en el momento de la cirugía, si se recomienda. Además, en los pacientes mayores de 50 años, debería considerarse su uso. Nivel de Evidencia: III, Estudio de Cohorte Restrospectiva.


Introduction: Knee arthroscopy is usually a safe procedure with few complications. The objective of this study is to calculate the incidence of symptomatic thromboembolic events: deep vein thrombosis and pulmonary thromboembolism, associated with knee arthroscopy and the possible related risk factors. Materials and Methods: Retrospective cohort that included all patients undergoing knee arthroscopy between January 2011 and December 2015 at a university hospital. Follow-up was 30 days after surgery. Demographic data, events of interest, type of surgery and possible risk factors were recorded. Results: 1,097 knee arthroscopies were performed in the 5 years. 100% had follow-up of at least 10 days, 90.5% reached follow-up of 30 days. The average follow-up time was 15.1 months. The percentage of thromboembolic events was 1.4% (n = 14). Two associated risk factors were found: previous thromboembolic events (p = 0.013) and use of anticoagulants prior to surgery (p = 0.001). The average age was higher in patients with thromboembolic events compared to those without events (58 vs 46 years), p = 0.009. Discussion: The incidence of symptomatic thromboembolic events after knee arthroscopy is low. The routine use of thromboembolic prophylaxis is not recommended. In patients with a history of previous thromboembolic events or who are on anticoagulation at the time of surgery, if recommended. Furthermore, its use should be considered in patients over 50 years of age. Level of Evidence: III, Retrospective Cohort Study.

18.
Rev. colomb. obstet. ginecol ; 72(3): 258-270, July-Sept. 2021. tab, graf
Article in Spanish | LILACS | ID: biblio-1351951

ABSTRACT

Objetivo: describir las características clínicas y la frecuencia de complicaciones maternas, fetales y neonatales, según técnica de anestesia neuroaxial (AN) en mujeres con síndrome de transfusión feto-fetal (STFF) tratadas con fotocoagulación láser (FL). Materiales y métodos: estudio de cohorte retrospectiva descriptivo. Se incluyeron gestantes con STFF tratadas con FL y AN en la Fundación Valle del Lili, Cali (Colombia) entre 2013-2017. Se excluyeron pacientes con STFF estadio-V de Quintero. Se usó estadística descriptiva. El protocolo fue aprobado por el Comité de Ética de la institución. Resultados: 32 participantes cumplieron con los criterios de inclusión y de exclusión. La población estuvo constituida por mujeres jóvenes, multíparas. En el 87,5% de los casos se realizó intervención de urgencia. El 43,7% presentaba el estadio-III de Quintero y en el 56,2 % de las gestantes se utilizó anestesia epidural. Las variables hemodinámicas maternas exhibieron un comportamiento similar, acorde al momento de la cirugía y la técnica neuoraxial implementada. El 65,6 % de las gestantes presentó hipotensión sostenida y el 9,3 % desarrolló edema pulmonar. El 65,6 % de las pacientes experimentó parto pretérmino y el 18,7 % ruptura prematura de membranas. Se registraron 14 muertes fetales y cinco neonatales. No se registraron casos de mortalidad materna. Conclusiones: en pacientes con STFF que requieren FL, el uso de la anestesia epidural, espinal o combinada probablemente se asocia con un comportamiento similar al de las variables hemodinámicas maternas, durante los momentos de la cirugía. Los profesionales que brindan atención a estas gestantes deben estar alerta ante la frecuente aparición de complicaciones maternas, fetales y neonatales. Se requieren estudios prospectivos que evalúen la seguridad y la efectividad de las diferentes técnicas de anestesia neuroaxial en pacientes con STFF.


Objective: To describe the clinical characteristics and the frequency of maternal, fetal and neonatal complications in accordance with the neuraxial anesthesia (NA) technique in women with twin-to- twin transfusion syndrome (TTTS) treated with laser photocoagulation. Materials and Methods: Descriptive retrospective cohort study of pregnant patients with TTTS treated with laser photocoagulation under NA at Fundación Valle del Lili, Cali (Colombia), between 2013-2017. Patients with Quintero stage VTTTS were excluded. The protocol was approved by the institutional ethics committee. Results: Of the participants, 32 met the inclusion and exclusion criteria. The study population consisted of young, multiparous women. Urgent interventions were performed in 87.5% of cases; 43.7% were Quintero stage III and epidural anesthesia was used in 56.2% of the women. Maternal hemodynamic variables were similar, in accordance with the timing of surgery and the neuraxial technique used. Sustained hypotension occurred in 65.6% of the pregnant women and 9.3% developed pulmonary edema. Pre-term delivery occurred in 65.6% of the patients and 18.7% had premature rupture of membranes. There were 14 fetal demises and five neonatal deaths. There were no cases of maternal mortality. Conclusions: In patients with TTTS requiring laser photocoagulation, the use of epidural, spinal or combined anesthesia is likely associated with similar maternal hemodynamic variables at the time of surgery. Practitioners providing care to these pregnant women must be aware of the frequent occurrence of maternal, fetal and neonatal complications. Prospective studies to assess the safety and effectiveness of the different neuraxial anesthesia techniques in patients with TTTS are required.


Subject(s)
Female , Pregnancy , Infant, Newborn , Fetofetal Transfusion , Pregnancy, Twin , Anesthesia, Epidural , Anesthesia, Spinal , Safety , Syndrome , Laser Coagulation , Fetoscopy , Anesthesia
20.
Rev. Univ. Ind. Santander, Salud ; 51(4): 309-315, Septiembre 26, 2019. tab, graf
Article in Spanish | LILACS | ID: biblio-1092261

ABSTRACT

Resumen Introducción: Es importante conocer las características demográficas y clínicas de las fracturas en niños para mejorar las estrategias de prevención y tratamiento en estos pacientes. Objetivos: Describir las fracturas en niños y sus características epidemiológicas. Metodología: Estudio tipo corte transversal desde enero 2014 hasta diciembre 2017. Pacientes menores de 18 años que consultaron por fracturas a una clínica en Colombia fueron incluidos. Se incluyeron datos demográficos, lugar donde ocurrió el trauma, huesos fracturados y tipo de tratamiento. Se evaluó la distribución por género y grupo etario. La fuente de información fue la historia clínica. Se utilizaron medidas de tendencia central y dispersión para agrupar los datos. Se calculó la incidencia de fracturas por cada 1000 niños/ año. Este estudio recibió aval del comité de ética de la institución. Resultados: Hubo 2436 niños fracturados, 65.6% (n=1597) ocurrieron en hombres. La mayoría fueron entre 6-11 años (40.7%, n=991), luego entre 12-17 años (36.4%, n=887) y finalmente, menores de 6 años (22.9%, n=558). La localización de la fractura más frecuente entre 0-5 años fue el húmero (30.6%, n=171), seguido por el radio (29%, n=162) y la clavícula (15.9%, n=89); entre 6-11 años fue el radio (45.2%, n=448), seguido por el húmero (18%, n=178) y el cúbito (16.6%, n=165); y entre 12-17 años fue el radio (34.6%, n=307), seguido por los huesos de la mano (22.7%, n=201) y los huesos del pie (10.8%, n=96). Requirieron manejo quirúrgico 30.9% de los niños fracturados (n=752). La incidencia de fracturas fue de 29.7/1000 niños por año. Conclusión: Las fracturas en niños se presentan con mayor frecuencia en el género masculino. Los huesos fracturados varían dependiendo del grupo etario, con un porcentaje importante del radio en todos los grupos. La mayoría se manejan de forma conservadora.


Abstract Introduction: It is important to know the demographic and clinical characteristics of fractures in children to improve prevention and treatment strategies in these patients. Objectives: To describe fractures in children and their epidemiological characteristics. Methodology: Cross-sectional study performed between January 2014 and December 2017. Patients under 18 years old with fractures who consulted to a hospital in Colombia were included. Demographic data, the location where the trauma occurred, fractured bones and type of treatment were included. Age and gender distribution were analyzed. Medical records were the source of information. Central tendency and dispersion measures were used to group the data. Incidence of fractures per 1000 children / year was calculated. This study received approval from the institution's ethics committee. Results: There were 2436 children with fractures, 65.6% (n=1597) occurred in males. Most fractures were in children between 6-11 years old (40.7%, n=991), followed by 12-17 years old (36.4%, n=887) and finally by children under 6 years old (22.9%, n=558). For the group under 6 years, most fractures occurred in humerus (30.6%, n=171), followed by radius (29%, n=162) and clavicle (15.9%, n=89); between 6-11 years old it was in radius (45.2%, n=448), followed by humerus (18%, n=178) and ulna (16.6%, n=165); and between 12-17 years it was in radio (34.6%, n=307), followed by bones of the hand (22.7%, n=201) and bones of the foot (10.8%, n=96). Surgical treatment was required in 30.9% (n=752) of the patients. The incidence of fractures was 29.7/1000 children per year. Conclusions: Fractures in children occur more frequently in males. The fractured bones differ depending on the age group; however, radius fractures represent an important proportion in all groups. Most fractures in children are treated in a conservative manner.


Subject(s)
Humans , Fractures, Bone , Child , Epidemiology , Closed Fracture Reduction , Open Fracture Reduction , Fracture Fixation
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