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1.
Fish Physiol Biochem ; 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38639895

RESUMO

Identification of specific molecular markers for spermatogonial stem cells in teleost is crucial for enhancing the efficacy of reproductive biotechnologies in aquaculture, such as transplantation and surrogate production in fishes. Since it is not yet possible to distinguish spermatogonial stem cells of European eel (Anguilla anguilla) using specific molecular markers, we isolated spermatogonial cells from immature European eels to find these potential markers. We attempted this by studying three candidate genes: vasa, nanos2, and dnd1. Two vasa (vasa1 and vasa2) genes, nanos2, and dnd1 were identified, characterized, and studied in the muscle, testis, and isolated spermatogonia. Our results showed that vasa1 and vasa2 had the highest levels of expression when measured by qPCR. In situ hybridization and immunochemistry assays showed that the four genes were localized explicitly in type A spermatogonia. However, vasa1 and vasa2 exhibited stronger signals in the immature testicular tissue than the other two potential markers. According to this, vasa1 and vasa2 were found to be the most effective markers for spermatogonial cells in the European eel.

2.
Fish Physiol Biochem ; 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38324141

RESUMO

The current climate change situation could bring critical effects for marine species, especially those already considered endangered. Although some species can adapt fast to the environmental changes, it is necessary to get into the worst scenario and develop tools to anticipatedly assess the physiological effects of such environmental change. With this purpose, our study aims to determine the effect of a range of seawater temperatures and pHs on sperm motility in the European eel (Anguilla anguilla). Low seawater pH (6.5-7.4) decreased the eel sperm motility in comparison to the control (pH = 8.2). We also studied the combined effect of the pH of the artificial seminal plasma (the plasma where the sperm cells are suspended) with the pH of Artificial Sea Water (ASW, pH 7.8 or and 8.2). We did not find statistical differences in sperm motility and kinetic parameters caused by the artificial seminal plasma pH. However, seawater pH induced significantly higher values of total sperm motility, and the percentage of fast spermatozoa with a pH of 8.2 in comparison with a pH of 7.8. In contrast, the seawater temperature did not affect sperm motility parameters or sperm longevity. To study the effect of the interaction between seawater temperature and pH on sperm motility, two temperatures: 4 and 24 °C, and two pHs 7.8 and 8.2, were tested. There were significant differences between temperature and pH in several kinetic parameters and, in general, the lowest values were observed in the samples activated at low temperature and low pH (4 °C, pH 7.8). This work suggest that eel sperm motility and kinetics will not be affected by the expected changes in pH or temperature due to the climate change.

3.
Heliyon ; 10(2): e24655, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38298628

RESUMO

The main function of the renin-angiotensin-aldosterone system (RAAS) is the regulation of blood pressure; therefore, researchers have focused on its study to treat cardiovascular and renal diseases. One of the most widely used treatments derived from the study of RAAS, is the use of angiotensin-converting enzyme inhibitors (ACEi). Since it was discovered, the main target of ACEi has been the cardiovascular and renal systems. However, being the RAAS expressed locally in several specialized tissues and cells such as pneumocytes, hepatocytes, spleenocytes, enterocytes, adipocytes, and neurons the effect of inhibitors has expanded, because it is expected that RAAS has a role in the specific function of those cells. Many chronic degenerative diseases compromise the correct function of those organs, and in most of them, the RAAS is overactivated. Therefore, the use of ACEi must exert a benefit on an impaired system. Accordingly, the objective of this review is to present a brief overview of the cardiovascular and renal actions of ACEi and its effects in organs that are not the classic targets of ACEi that carry on glucose and lipid metabolism.

4.
J Med Chem ; 67(4): 2321-2336, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38300987

RESUMO

Bruton's tyrosine kinase (BTK), a member of the TEC family of kinases, is an essential effector of B-cell receptor (BCR) signaling. Chronic activation of BTK-mediated BCR signaling is a hallmark of many hematological malignancies, which makes it an attractive therapeutic target. Pharmacological inhibition of BTK enzymatic function is now a well-proven strategy for the treatment of patients with these malignancies. We report the discovery and characterization of NX-2127, a BTK degrader with concomitant immunomodulatory activity. By design, NX-2127 mediates the degradation of transcription factors IKZF1 and IKZF3 through molecular glue interactions with the cereblon E3 ubiquitin ligase complex. NX-2127 degrades common BTK resistance mutants, including BTKC481S. NX-2127 is orally bioavailable, exhibits in vivo degradation across species, and demonstrates efficacy in preclinical oncology models. NX-2127 has advanced into first-in-human clinical trials and achieves deep and sustained degradation of BTK following daily oral dosing at 100 mg.


Assuntos
Inibidores de Proteínas Quinases , Proteínas Tirosina Quinases , Humanos , Tirosina Quinase da Agamaglobulinemia , Inibidores de Proteínas Quinases/efeitos adversos , Transdução de Sinais
5.
Cardiol Young ; 34(4): 722-726, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37743785

RESUMO

BACKGROUND: The Fontan procedure is considered one of the most remarkable achievements in paediatric cardiology and cardiac surgery. Its final anatomical objective is a venous return through the superior and inferior vena cava. The complications inherent to this procedure and subsequent failure are its limitations. OBJECTIVE: To describe the clinical and haemodynamic characteristics of patients with Fontan failure and define the risk factors associated with it, with its short- and long-term outcomes during a 21-year observation period. METHODS: This is a retrospective follow-up study in which 15 patients diagnosed with Fontan failure in the single-ventricle programme of a high-complexity hospital in Medellín, Colombia, between 2001 and 2022 were included. RESULTS: One hundred and eight patients were identified in whom the Fontan procedure was performed, and 17 met the failure criteria. 82.4% were men, with a median age of 4.3 years. Ebstein's anomaly was the most common diagnosis, 29.4%. All patients underwent Fontan with an extracardiac tube following the procedure. According to the type of failure, 58.8% of patients presented protein-losing enteropathy and 17.6% plastic bronchitis. During follow-up, 5.9% of patients died. CONCLUSION: Fontan surgery in our centre is an option for patients with univentricular physiology. The correct selection of the patient is essential to mitigate failure risks.


Assuntos
Técnica de Fontan , Cardiopatias Congênitas , Enteropatias Perdedoras de Proteínas , Criança , Masculino , Humanos , Pré-Escolar , Feminino , Técnica de Fontan/efeitos adversos , Técnica de Fontan/métodos , Colômbia/epidemiologia , Seguimentos , Estudos Retrospectivos , Cardiopatias Congênitas/cirurgia , Cardiopatias Congênitas/complicações , Fatores de Risco , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Enteropatias Perdedoras de Proteínas/etiologia
6.
Med. clín (Ed. impr.) ; 161(6): 238-242, sept. 2023. tab
Artigo em Inglês | IBECS | ID: ibc-225544

RESUMO

Objective To determine the presence of human papillomavirus (HPV) in the oral mucosa of blood donors (BD) and risk factors associated with HPV and oral cancer. Materials and methods Prospective cross-sectional study, population matched to BD from the National Cancer Institute, Mexico for HPV identification in oral cytological samples using the CLART® Human Papillomavirus 2 Kit (35 genotypes) and risk factors. Results Of 352 BD with signed informed consent, 285 were selected by simple randomization. The prevalence of oral HPV was 17.5% (95% CI 13–21.9%), the genotype was identified in 13 cases, with a total of 16 genotypes (10 high-risk), the most common being 16 and 84. Five cases had multiple infections, three with at least one high-risk type. Associations were found for marital status (OR 3.3) and educational level (OR-1.9). Conclusions The percentage of HPV-positive cases in blood donors with no risk practices was similar to that found in Spanish-speaking population studies in which at least one risk practice was described. The presence of other genotypes with high oncogenic risk and multitype infection, described as a marker of persistence of HPV infection, is highlighted (AU)


Objetivo Identificar la presencia del virus del papiloma humano (VPH) en la mucosa oral de donantes de sangre (DS), así como los factores de riesgo relacionados con el VPH y el cáncer oral. Materiales y métodos Estudio transversal prospectivo. La población correspondió a los DS del Instituto Nacional de Cancerología, México, para la identificación de VPH en muestras citológicas orales con el kit CLART® Human Papillomavirus 2 (35 genotipos) y factores de riesgo. Resultados De 352 DS con firma de consentimiento informado, se seleccionaron 285 por aleatorización simple. La prevalencia de VPH oral fue del 17,5% (IC 95%: 13-21,9%); en 13 casos se identificó el genotipo, con un total de 16 genotipos (10 de alto riesgo), los más frecuentes el 16 y el 84. Cinco casos presentaron infección multitipo, 3 con al menos un tipo de alto riesgo. Las asociaciones encontradas fueron para el estado civil (OR 3,3) y el nivel de estudios (OR 1,9). Conclusiones El porcentaje de casos positivos para VPH en DS sin prácticas de riesgo fue similar a los hallazgos en estudios de población hispanohablante en los que se ha descrito al menos una práctica de riesgo. Se destaca la presencia de otros genotipos con alto riesgo oncogénico y la infección multitipo descrita como marcador de persistencia de la infección por VPH (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Mucosa Bucal/virologia , Doadores de Sangue , Estudos Transversais , Estudos Prospectivos , Prevalência , Genótipo
7.
Int J Mol Sci ; 24(16)2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37628828

RESUMO

Acid sphingomyelinase deficiency (ASMD) or Niemann-Pick disease type A (NPA), type B (NPB) and type A/B (NPA/B), is a rare lysosomal storage disease characterized by progressive accumulation of sphingomyelin (SM) in the liver, lungs, bone marrow and, in severe cases, neurons. A disease model was established by generating liver organoids from a NPB patient carrying the p.Arg610del variant in the SMPD1 gene. Liver organoids were characterized by transcriptomic and lipidomic analysis. We observed altered lipid homeostasis in the patient-derived organoids showing the predictable increase in sphingomyelin (SM), together with cholesterol esters (CE) and triacylglycerides (TAG), and a reduction in phosphatidylcholine (PC) and cardiolipins (CL). Analysis of lysosomal gene expression pointed to 24 downregulated genes, including SMPD1, and 26 upregulated genes that reflect the lysosomal stress typical of the disease. Altered genes revealed reduced expression of enzymes that could be involved in the accumulation in the hepatocytes of sphyngoglycolipids and glycoproteins, as well as upregulated genes coding for different glycosidases and cathepsins. Lipidic and transcriptome changes support the use of hepatic organoids as ideal models for ASMD investigation.


Assuntos
Doença de Niemann-Pick Tipo A , Doenças de Niemann-Pick , Humanos , Doença de Niemann-Pick Tipo A/genética , Esfingomielinas , Fígado , Expressão Gênica
8.
Int J Mol Sci ; 24(15)2023 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-37569847

RESUMO

Different mutations in the SERPINA1 gene result in alpha-1 antitrypsin (AAT) deficiency and in an increased risk for the development of liver diseases. More than 90% of severe deficiency patients are homozygous for Z (Glu342Lys) mutation. This mutation causes Z-AAT polymerization and intrahepatic accumulation which can result in hepatic alterations leading to steatosis, fibrosis, cirrhosis, and/or hepatocarcinoma. We aimed to investigate lipid status in hepatocytes carrying Z and normal M alleles of the SERPINA1 gene. Hepatic organoids were developed to investigate lipid alterations. Lipid accumulation in HepG2 cells overexpressing Z-AAT, as well as in patient-derived hepatic organoids from Pi*MZ and Pi*ZZ individuals, was evaluated by Oil-Red staining in comparison to HepG2 cells expressing M-AAT and liver organoids from Pi*MM controls. Furthermore, mass spectrometry-based lipidomics analysis and transcriptomic profiling were assessed in Pi*MZ and Pi*ZZ organoids. HepG2 cells expressing Z-AAT and liver organoids from Pi*MZ and Pi*ZZ patients showed intracellular accumulation of AAT and high numbers of lipid droplets. These latter paralleled with augmented intrahepatic lipids, and in particular altered proportion of triglycerides, cholesterol esters, and cardiolipins. According to transcriptomic analysis, Pi*ZZ organoids possess many alterations in genes and cellular processes of lipid metabolism with a specific impact on the endoplasmic reticulum, mitochondria, and peroxisome dysfunction. Our data reveal a relationship between intrahepatic accumulation of Z-AAT and alterations in lipid homeostasis, which implies that liver organoids provide an excellent model to study liver diseases related to the mutation of the SERPINA1 gene.


Assuntos
Deficiência de alfa 1-Antitripsina , alfa 1-Antitripsina , Humanos , Deficiência de alfa 1-Antitripsina/genética , Deficiência de alfa 1-Antitripsina/complicações , Lipídeos , Cirrose Hepática/etiologia , Organoides , alfa 1-Antitripsina/genética
9.
Biomedicines ; 11(7)2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37509601

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a type of steatosis commonly associated with obesity, dyslipidemia, hypertension, and diabetes. Other diseases such as inherited alpha-1 antitrypsin deficiency (AATD) have also been related to the development of liver steatosis. The primary reasons leading to hepatic lipid deposits can be genetic and epigenetic, and the outcomes range from benign steatosis to liver failure, as well as to extrahepatic diseases. Progressive hepatocellular damage and dysregulated systemic immune responses can affect extrahepatic organs, specifically the heart and lungs. In this review, we discuss the similarities and differences between the molecular pathways of NAFLD and AATD, and the putative value of hepatic organoids as novel models to investigate the physio pathological mechanisms of liver steatosis.

10.
Front Plant Sci ; 14: 1195794, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37441182

RESUMO

Introduction: The fungal pathogen Fusarium verticillioides (Sacc.) Nirenberg (Fv) causes considerable agricultural and economic losses and is harmful to animal and human health. Fv can infect maize throughout its long agricultural cycle, and root infection drastically affects maize growth and yield. Methods: The root cell wall is the first physical and defensive barrier against soilborne pathogens such as Fv. This study compares two contrasting genotypes of maize (Zea mays L.) roots that are resistant (RES) or susceptible (SUS) to Fv infection by using transcriptomics, fluorescence, scanning electron microscopy analyses, and ddPCR. Results: Seeds were infected with a highly virulent local Fv isolate. Although Fv infected both the RES and SUS genotypes, infection occurred faster in SUS, notably showing a difference of three to four days. In addition, root infections in RES were less severe in comparison to SUS infections. Comparative transcriptomics (rate +Fv/control) were performed seven days after inoculation (DAI). The analysis of differentially expressed genes (DEGs) in each rate revealed 733 and 559 unique transcripts that were significantly (P ≤0.05) up and downregulated in RES (+Fv/C) and SUS (+Fv/C), respectively. KEGG pathway enrichment analysis identified coumarin and furanocoumarin biosynthesis, phenylpropanoid biosynthesis, and plant-pathogen interaction pathways as being highly enriched with specific genes involved in cell wall modifications in the RES genotype, whereas the SUS genotype mainly displayed a repressed plant-pathogen interaction pathway and did not show any enriched cell wall genes. In particular, cell wall-related gene expression showed a higher level in RES than in SUS under Fv infection. Analysis of DEG abundance made it possible to identify transcripts involved in response to abiotic and biotic stresses, biosynthetic and catabolic processes, pectin biosynthesis, phenylpropanoid metabolism, and cell wall biosynthesis and organization. Root histological analysis in RES showed an increase in lignified cells in the sclerenchymatous hypodermis zone during Fv infection. Discussion: These differences in the cell wall and lignification could be related to an enhanced degradation of the root hairs and the epidermis cell wall in SUS, as was visualized by SEM. These findings reveal that components of the root cell wall are important against Fv infection and possibly other soilborne phytopathogens.

11.
Med Clin (Barc) ; 161(6): 238-242, 2023 09 29.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-37353414

RESUMO

OBJECTIVE: To determine the presence of human papillomavirus (HPV) in the oral mucosa of blood donors (BD) and risk factors associated with HPV and oral cancer. MATERIALS AND METHODS: Prospective cross-sectional study, population matched to BD from the National Cancer Institute, Mexico for HPV identification in oral cytological samples using the CLART® Human Papillomavirus 2 Kit (35 genotypes) and risk factors. RESULTS: Of 352 BD with signed informed consent, 285 were selected by simple randomization. The prevalence of oral HPV was 17.5% (95% CI 13-21.9%), the genotype was identified in 13 cases, with a total of 16 genotypes (10 high-risk), the most common being 16 and 84. Five cases had multiple infections, three with at least one high-risk type. Associations were found for marital status (OR 3.3) and educational level (OR-1.9). CONCLUSIONS: The percentage of HPV-positive cases in blood donors with no risk practices was similar to that found in Spanish-speaking population studies in which at least one risk practice was described. The presence of other genotypes with high oncogenic risk and multitype infection, described as a marker of persistence of HPV infection, is highlighted.


Assuntos
Papillomavirus Humano , Infecções por Papillomavirus , Humanos , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Mucosa Bucal , Estudos Prospectivos , Estudos Transversais , Doadores de Sangue , Genótipo , Papillomaviridae/genética , Prevalência
12.
Polymers (Basel) ; 15(7)2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37050357

RESUMO

The rheological behavior of aqueous solutions of polyvinyl alcohol at 4, 6, 8 and 10% by weight has been studied and evaluated at temperatures of 20, 25, 30 and 35 °C, using five non-Newtonian fluid models independent of time: Ferrys, Robertson-Stiff, Williamson, Sisko, and Ellis de Haven. The classical method consists in carrying out regression analysis. Using a comparative procedure of determination coefficients and variances, the model that most appropriately adjusts the experimental data to said model is selected. From the statistical point of view, the Sisko and Robertson-Stiff models present better regression parameters; to better specify the choice of the respective rheological model, a new factor has been proposed in the literature, the viscosity factor (VF), which expresses the relationship between apparent and dynamic viscosity. The analysis of this factor for the five models confirms the greater stability of the Ellis de Haven model in terms of the coefficient of variation of the VF. The value of VF fluctuates between 1 and 2 for all ranges of temperature and concentration experienced for vinyl alcohol solutions. As a consequence of the above, for the choice of the non-Newtonian fluid model associated with the rheology of the aqueous solution of polyvinyl alcohol, it is necessary to analyze the statistical parameters and the VF factor simultaneously.

13.
Peptides ; 164: 171001, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36990388

RESUMO

Hyperglycemia (HG) impairs the renin-angiotensin system (RAS), which may contribute to vascular dysfunction. Besides, hydrogen sulfide (H2S) exerts beneficial cardiovascular effects in metabolic diseases. Therefore, our study aimed to determine the effects of chronic administration of sodium hydrosulfide (NaHS; inorganic H2S donor) and DL-Propargylglycine [DL-PAG; cystathionine-×¥-lyase (CSE) inhibitor] on the RAS-mediated vascular responses impairments observed in thoracic aortas from male diabetic Wistar rats. For that purpose, neonatal rats were divided into two groups that received: 1) citrate buffer (n = 12) or 2) streptozotocin (STZ, 70 mg/kg; n = 48) on the third postnatal day. After 12 weeks, diabetic animals were divided into 4 subgroups (n = 12 each) that received daily i.p. injections during 4 weeks of: 1) non-treatment; 2) vehicle (PBS, 1 mL/kg); 3) NaHS (5.6 mg/kg); and 4) DL-PAG (10 mg/kg). After treatments (16 weeks), blood glucose, angiotensin-(1-7) [Ang-(1-7)], and angiotensin II (Ang II) levels, vascular responses to Ang-(1-7) and Ang II, and the expression of angiotensin AT1, AT2, and Mas receptors, angiotensin converting enzyme (ACE) and ACE type 2 (ACE2) were determined. HG induced: 1) increased blood glucose levels and expression of angiotensin II AT1 receptor; 2) impaired Ang-(1-7) and Ang II mediated vascular responses; 3) decreased angiotensin levels and expression of angiotensin II AT2 and angiotensin-(1-7) Mas receptors, and ACE2; and 4) no changes in ACE expression. Interestingly, NaHS, but not DL-PAG, reversed HG-induced impairments, except for blood glucose level changes. These results suggest that NaHS restores vascular function in streptozotocin-induced HG through RAS modulation.


Assuntos
Hiperglicemia , Sistema Renina-Angiotensina , Ratos , Masculino , Animais , Angiotensina II/metabolismo , Enzima de Conversão de Angiotensina 2/metabolismo , Glicemia , Estreptozocina/farmacologia , Ratos Wistar , Peptidil Dipeptidase A/metabolismo , Hiperglicemia/induzido quimicamente , Hiperglicemia/tratamento farmacológico , Hiperglicemia/metabolismo , Angiotensina I/farmacologia
14.
J Immunotoxicol ; 20(1): 2175078, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36773297

RESUMO

Immunogenic cell death (ICD) is a form of cell death characterized by the release of danger signals required to trigger an adaptive immune response against tumor-associated antigens. Silver nanoparticles (AgNP) display anti-proliferative and cytotoxic effects in tumor cells, but it has not been previously studied whether AgNP act as an ICD inductor. The present study evaluated the in vitro release of calreticulin as a damage-associated molecular pattern (DAMP) associated with the cytotoxicity of AgNP and their in vivo anti-cancer effects. In vitro, mouse CT26 colon carcinoma and MCA205 fibrosarcoma cells were exposed to AgNP and then cell proliferation, adhesion, and release of calreticulin were determined. The results indicated there were time- and concentration-related anti-proliferative effects of AgNP in both the CT26 and MCA205 lines. Concurrently, changes in cell adhesion were detected mainly in the CT26 cells. Regarding DAMP detection, a significant increase in calreticulin was observed only in CT26 cells treated with doxorubicin and AgNP; however, no differences were found in the MCA205 cells. In vivo, the survival and growth of subcutaneous tumors were monitored after vaccination of mice with cell debris from tumor cells treated with AgNP or after intra-tumoral administration of AgNP to established tumors. Consequently, anti-tumoral prophylactic immunization with AgNP-dead cells failed to protect mice from tumor re-challenge; intra-tumor injection of AgNP did not induce a significant effect. In conclusion, there was a noticeable anti-tumoral effect of AgNP in vitro in both CT26 and MCA205 cell lines, accompanied by the release of calreticulin in CT26 cells. In vivo, immunization with cell debris derived from AgNP-treated tumor cells failed to induce a protective immune response in the cancer model mice. Clearly, further research is needed to determine if one could combine AgNP with other ICD inducers to improve the anti-tumor effect of these nanoparticles in vivo.


Assuntos
Antineoplásicos , Nanopartículas Metálicas , Camundongos , Animais , Calreticulina/metabolismo , Calreticulina/farmacologia , Prata , Morte Celular Imunogênica , Morte Celular , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral
15.
J Leukoc Biol ; 113(1): 58-70, 2023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-36822165

RESUMO

Rodent models of lipopolysaccharide (LPS)-induced pulmonary inflammation are used for anti-inflammatory drug testing. We aimed to characterize mice responses to aerosolized LPS alone or with intraperitoneal (i.p.) delivery of alpha1-antitrypsin (AAT). Balb/c mice were exposed to clean air or aerosolized LPS (0.21 mg/mL) for 10 min per day, for 3 d. One hour after each challenge, animals were treated i.p. with saline or with (4 mg/kg body weight) one of the AAT preparations: native (AAT), oxidized (oxAAT), recombinant (recAAT), or peptide of AAT (C-36). Experiments were terminated 6 h after the last dose of AATs. Transcriptome data of mice lungs exposed to clean air versus LPS revealed 656 differentially expressed genes and 155 significant gene ontology terms, including neutrophil migration and toll-like receptor signaling pathways. Concordantly, mice inhaling LPS showed higher bronchoalveolar lavage fluid neutrophil counts and levels of myeloperoxidase, inducible nitric oxide synthase, IL-1ß, TNFα, KC, IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF). Plasma inflammatory markers did not increase. After i.p. application of AATs, about 1% to 2% of proteins reached the lungs but, except for GM-CSF, none of the proteins significantly influenced inflammatory markers. All AATs and C-36 significantly inhibited LPS-induced GM-CSF release. Surprisingly, only oxAAT decreased the expression of several LPS-induced inflammatory genes, such as Cxcl3, Cd14, Il1b, Nfkb1, and Nfkb2, in lung tissues. According to lung transcriptome data, oxAAT mostly affected genes related to transcriptional regulation while native AAT or recAAT affected genes of inflammatory pathways. Hence, we present a feasible mice model of local lung inflammation induced via aerosolized LPS that can be useful for systemic drug testing.


Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos , Pneumonia , alfa 1-Antitripsina , Animais , Humanos , Camundongos , Líquido da Lavagem Broncoalveolar , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Lipopolissacarídeos/efeitos adversos , Pulmão/metabolismo , Pneumonia/induzido quimicamente , Pneumonia/tratamento farmacológico , alfa 1-Antitripsina/uso terapêutico
16.
Perfusion ; 38(2): 405-409, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-34617859

RESUMO

INTRODUCTION: Data on extra-corporeal membrane oxygenation (ECMO) therapy for pregnant patients with Coronavirus 2019 (COVID-19) infection are limited. Here we report a case of an emergency cesarean section performed while the COVID-19 positive mother was on ECMO support. CASE REPORT: A 36-year-old COVID-19 positive patient at 26 weeks gestational age presented with respiratory failure requiring extra-corporeal membrane oxygenation therapy. Nine days later fetal distress demanded an emergency C-section. After 5 weeks on ECMO, the patient was weaned off. Both mother and child were discharged. DISCUSSION: The decision to perform an urgent C-section is one that requires meticulous thought from the attending team. Pulmonary maturation is key as pregnancy may need to be terminated at any time during ECMO. CONCLUSION: Data on ECMO support for pregnant patients with COVID-19 infection are scarce. Best results can be achieved ensuring adequate anticoagulation, meticulous choice of cannulas, continued fetal monitoring, early lung maturation, and precision timing of delivery.


Assuntos
COVID-19 , Oxigenação por Membrana Extracorpórea , Insuficiência Respiratória , Criança , Humanos , Gravidez , Feminino , Adulto , COVID-19/terapia , Oxigenação por Membrana Extracorpórea/métodos , Cesárea , Pulmão
17.
Curr Probl Cardiol ; 48(1): 101431, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36167227

RESUMO

The prevalence of Heart Failure is growing alarmingly; its treatment consumes health resources and affects the quality of life of patients. To describe the changes in NYHA functional Class, ejection fraction, hospitalizations, and mortality after 8 years of follow up in a multidisciplinary heart failure program in Colombia as a model for lower and middle income countries. An observational study was performed with the retrospective analysis of the information. 1757 patients were included, The NYHA functional class at the beginning of the program was: NYHA I 23.5%, NYHA II 50.3%, NYHA class Improvement was observed at the end of the follow-up with an increase in the percentage of patients in Functional Class NYHA I and II. The reduction in hospitalizations were 35% less (mean: 0.68 ± 0.95, P < 0.0001), a reduction in the length of stay in the hospital was 13.2% (before: 4.46 ± 7.16, after 3.87 ± 8.1 days, P < 0.001). The total mortality after eight years of follow-up was 6.6 % (n = 116). Multidisciplinary follow-up in Heart Failure (HF) programs improves Functional Class and EF, decreases hospital admissions as well as hospitalization and the length of stay. This is a very simple and successful model of care for this disease that can be implemented for countries of lower- and middle-income countries.


Assuntos
Insuficiência Cardíaca , Qualidade de Vida , Humanos , Estudos Retrospectivos , Colômbia/epidemiologia , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/terapia , Volume Sistólico , Estudos Observacionais como Assunto
19.
Forensic Sci Int ; 341: 111478, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36283277

RESUMO

This research proposes a methodological approach to search floating bodies or floating body parts in rivers using hydroinformatic tools. These tools may allow possible search locations and potential release sites to be determined. The approach draws from hydrometric field information, two-dimensional (2D) hydrodynamic modeling, particle tracking (PT) models, and large-scale particle image velocimetry (LSPIV). This methodology was applied to a case study of the La Miel river in Colombia, where existing reports of deceased persons are available. A series of hydraulic accidents have been defined to represent the hydrodynamic and transport processes that occur in such situations. The results indicate that potential search locations, namely places where human floating bodies or floating body parts may be found, are principally on the left and right shores of recirculation systems.


Assuntos
Hidrodinâmica , Rios , Humanos , Reologia , Colômbia , Monitoramento Ambiental/métodos
20.
Biomédica (Bogotá) ; 42(supl.2): 73-77, oct. 2022. tab
Artigo em Inglês | LILACS | ID: biblio-1403614

RESUMO

Introduction: More than 90% of children infected with COVID-19 worldwide developed mild to moderate disease. In Colombia, during 2020, COVID-19 infections in children stayed below 9.2% of the total cases, with no trends for age group or sex. Objective: To estimate the incidence of acute respiratory symptoms and COVID-19 in children from public schools in Bogotá, Colombia during the second semester of 2020. Material and methods: A telephone survey was conducted in over 5,000 scholar children. Antecedents and use of health services were informed. Descriptive statistics were used. Results: A total of 151.470 persons per day accounting for an IR of 157,8 per 100,000 people; almost three times the rate reported by the official surveillance system in the city. Conclusion: A lack of diagnosis and consultation in children was found compared to the general population. Further research is needed to elucidate the true burden of the disease in children.


Introducción. Más del 90% de los niños infectados con COVID-19 en el mundo, desarrollaron enfermedad leve a moderada. En Colombia, durante el 2020, la infección del COVID-19 en niños se mantuvo por debajo de 9,2 % del total de los casos sin tendencias por grupo de edad o sexo. Objetivo. Estimar la incidencia de síntomas respiratorios agudos y COVID19 en niños de escuelas públicas en Bogotá (Colombia) durante el segundo semestre de 2020. Materiales y métodos. Se hizo una encuesta telefónica en más de 5.000 escolares. Se recolectó información de antecedentes médicos y uso de servicios de salud. La información obtenida se describió mediante estadística descriptiva. Resultados. Se contabilizó un total de 151.470 personas al día para una tasa de incidencia de 157,8 en 100.000 personas, casi tres veces la tasa reportada por el sistema de vigilancia oficial de la ciudad. Conclusión. Se encontraron deficiencias en el diagnóstico y consulta de los niños, al compararlos con la población general. Se necesita más investigación para dilucidar la verdadera carga de la enfermedad en la población infantil.


Assuntos
Criança , Adolescente , Infecções por Coronavirus , Infecções Respiratórias , Epidemiologia , Doenças Transmissíveis , Vigilância em Desastres
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