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1.
Biomed Res Int ; 2022: 1522426, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35013710

RESUMO

Several therapeutic regimens for COVID-19 have been studied, such as combination antiviral therapies. We aimed to compare outcome of two types of combination therapies atazanavir/ritonavir (ATV/r) or lopinavir/ritonavir (LPV/r) plus hydroxychloroquine among COVID-19 patients. 108 patients with moderate and severe forms of COVID-19 were divided into two groups (each group 54 patients). One group received ATV/r plus hydroxychloroquine, and the other group received hydroxychloroquine plus LPV/r. Then, both groups were evaluated and compared for clinical symptoms, recovery rates, and complications of treatment regimens. Our findings showed a significant increase in bilirubin in ATV/r-receiving group compared to LPV/r receivers. There was also a significant increase in arrhythmias in the LPV/r group compared to the ATV/r group during treatment. Other findings including length of hospital stay, outcome, and treatment complications were not statistically significant. There is no significant difference between protease inhibitor drugs including ATV/r and LPV/r in the treatment of COVID-19 regarding clinical outcomes. However, some side effects such as hyperbilirubinemia and arrhythmia were significantly different by application of atazanavir or lopinavir.


Assuntos
Sulfato de Atazanavir/uso terapêutico , COVID-19/tratamento farmacológico , Lopinavir/uso terapêutico , Ritonavir/uso terapêutico , Idoso , Antivirais/uso terapêutico , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/fisiopatologia , Bilirrubina/análise , COVID-19/metabolismo , Combinação de Medicamentos , Quimioterapia Combinada/métodos , Feminino , Hospitalização/tendências , Humanos , Hidroxicloroquina/uso terapêutico , Tempo de Internação/tendências , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/patogenicidade , Resultado do Tratamento
2.
Invest Ophthalmol Vis Sci ; 63(1): 3, 2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-34982147

RESUMO

Purpose: Amblyopia is diagnosed as a reduced acuity in an otherwise healthy eye, which indicates that the deficit is not happening in the eye, but in the brain. One suspected mechanism explaining these deficits is an elevated amount of intrinsic blur in the amblyopic visual system compared to healthy observers. This "internally produced blur" can be estimated by the "equivalent intrinsic blur method", which measures blur discrimination thresholds while systematically increasing the external blur in the physical stimulus. Surprisingly, amblyopes do not exhibit elevated intrinsic blur when measured with an edge stimulus. Given the fundamental ways in which they differ, synthetic stimuli, such as edges, are likely to generate contrasting blur perception compared to natural stimuli, such as pictures. Because our visual system is presumably tuned to process natural stimuli, testing artificial stimuli only could result in performances that are not ecologically valid. Methods: We tested this hypothesis by measuring, for the first time, the perception of blur added to natural images in amblyopia and compared discrimination performance for natural images and synthetic edges in healthy and amblyopic groups. Results: Our results demonstrate that patients with amblyopia exhibit higher levels of intrinsic blur than control subjects when tested on natural images. This difference was not observed when using edges. Conclusions: Our results suggest that intrinsic blur is elevated in the visual system representing vision from the amblyopic eye and that distinct statistics of images can generate different blur perception.


Assuntos
Ambliopia/fisiopatologia , Erros de Refração/fisiopatologia , Percepção Visual/fisiologia , Adulto , Idoso , Esotropia/fisiopatologia , Exotropia/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Refração Ocular/fisiologia , Limiar Sensorial/fisiologia , Acuidade Visual/fisiologia , Adulto Jovem
3.
Invest Ophthalmol Vis Sci ; 63(1): 7, 2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-34989761

RESUMO

Purpose: Dry eye-induced chronic ocular pain is also called ocular neuropathic pain. However, details of the pathogenic mechanism remain unknown. The purpose of this study was to elucidate the pathogenic mechanism of dry eye-induced chronic pain in the anterior eye area and develop a pathophysiology-based therapeutic strategy. Methods: We used a rat dry eye model with lacrimal gland excision (LGE) to elucidate the pathogenic mechanism of ocular neuropathic pain. Corneal epithelial damage, hypersensitivity, and hyperalgesia were evaluated on the LGE side and compared with the sham surgery side. We analyzed neuronal activity, microglial and astrocytic activity, α2δ-1 subunit expression, and inhibitory interneurons in the trigeminal nucleus. We also evaluated the therapeutic effects of ophthalmic treatment and chronic pregabalin administration on dry eye-induced ocular neuropathic pain. Results: Dry eye caused hypersensitivity and hyperalgesia on the LGE side. In the trigeminal nucleus of the LGE side, neuronal hyperactivation, transient activation of microglia, persistent activation of astrocytes, α2δ-1 subunit upregulation, and reduced numbers of inhibitory interneurons were observed. Ophthalmic treatment alone did not improve hyperalgesia. In contrast, continuous treatment with pregabalin effectively ameliorated hypersensitivity and hyperalgesia and normalized neural activity, α2δ-1 subunit upregulation, and astrocyte activation. Conclusions: These results suggest that dry eye-induced hypersensitivity and hyperalgesia are caused by central sensitization in the trigeminal nucleus with upregulation of the α2δ-1 subunit. Here, we showed that pregabalin is effective for treating dry eye-induced ocular neuropathic pain even after chronic pain has been established.


Assuntos
Analgésicos/administração & dosagem , Modelos Animais de Doenças , Síndromes do Olho Seco/fisiopatologia , Dor Ocular/fisiopatologia , Pregabalina/administração & dosagem , Administração Oftálmica , Animais , Astrócitos/patologia , Canais de Cálcio Tipo L/metabolismo , Doença Crônica , Córnea/inervação , Síndromes do Olho Seco/tratamento farmacológico , Dor Ocular/tratamento farmacológico , Ácido Hialurônico/administração & dosagem , Hiperalgesia/tratamento farmacológico , Hiperalgesia/fisiopatologia , Masculino , Microglia/patologia , Neuralgia/tratamento farmacológico , Neuralgia/fisiopatologia , Neurônios/metabolismo , Neurônios/patologia , Soluções Oftálmicas , Ratos , Ratos Sprague-Dawley , Nervo Trigêmeo/metabolismo , Nervo Trigêmeo/patologia
4.
Invest Ophthalmol Vis Sci ; 63(1): 6, 2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-34989762

RESUMO

Purpose: To assess whether monocular contrast sensitivity and stereoacuity impairments remain when visual acuity is fully recovered in children with refractive amblyopia. Methods: A retrospective review of 487 patients diagnosed with refractive amblyopia whose visual acuity improved to 0.08 logMAR or better in both eyes following optical treatment was conducted. Measurements of monocular contrast sensitivity and stereoacuity had been made when visual acuity normalized. All patients had been treated with refractive correction for approximately 2 years following diagnosis. No other treatments were provided. Monocular contrast sensitivity was measured using the CSV-1000E chart for children 6 years of age or younger and a psychophysical technique called the quick contrast sensitivity function in older children. Stereoacuity was measured using the Random Dot Test that includes monocular cues and the Randot Stereoacuity Test that does not have monocular cues. Results: Statistically significant interocular differences in contrast sensitivity were observed. These differences tended to occur at higher spatial frequencies (12 and 18 cycles per degree). Stereoacuity within the age-specific normal range was achieved by 47.4% of patients for the Random Dot Test and only 23.1% of patients for the Randot Stereoacuity Test. Conclusions: Full recovery of visual acuity following treatment for refractive amblyopia does not equalize interocular contrast sensitivity or restore normal stereopsis. Alternative therapeutic approaches that target contrast sensitivity and/or binocular vision are required.


Assuntos
Ambliopia/terapia , Sensibilidades de Contraste/fisiologia , Percepção de Profundidade/fisiologia , Óculos , Hiperopia/terapia , Miopia/terapia , Ambliopia/fisiopatologia , Criança , Pré-Escolar , Feminino , Humanos , Hiperopia/fisiopatologia , Masculino , Miopia/fisiopatologia , Estudos Retrospectivos , Privação Sensorial , Testes Visuais/métodos , Visão Binocular , Acuidade Visual
6.
BMC Pulm Med ; 22(1): 1, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34980061

RESUMO

BACKGROUND: Quantitative evaluation of radiographic images has been developed and suggested for the diagnosis of coronavirus disease 2019 (COVID-19). However, there are limited opportunities to use these image-based diagnostic indices in clinical practice. Our aim in this study was to evaluate the utility of a novel visually-based classification of pulmonary findings from computed tomography (CT) images of COVID-19 patients with the following three patterns defined: peripheral, multifocal, and diffuse findings of pneumonia. We also evaluated the prognostic value of this classification to predict the severity of COVID-19. METHODS: This was a single-center retrospective cohort study of patients hospitalized with COVID-19 between January 1st and September 30th, 2020, who presented with suspicious findings on CT lung images at admission (n = 69). We compared the association between the three predefined patterns (peripheral, multifocal, and diffuse), admission to the intensive care unit, tracheal intubation, and death. We tested quantitative CT analysis as an outcome predictor for COVID-19. Quantitative CT analysis was performed using a semi-automated method (Thoracic Volume Computer-Assisted Reading software, GE Health care, United States). Lungs were divided by Hounsfield unit intervals. Compromised lung (%CL) volume was the sum of poorly and non-aerated volumes (- 500, 100 HU). We collected patient clinical data, including demographic and clinical variables at the time of admission. RESULTS: Patients with a diffuse pattern were intubated more frequently and for a longer duration than patients with a peripheral or multifocal pattern. The following clinical variables were significantly different between the diffuse pattern and peripheral and multifocal groups: body temperature (p = 0.04), lymphocyte count (p = 0.01), neutrophil count (p = 0.02), c-reactive protein (p < 0.01), lactate dehydrogenase (p < 0.01), Krebs von den Lungen-6 antigen (p < 0.01), D-dimer (p < 0.01), and steroid (p = 0.01) and favipiravir (p = 0.03) administration. CONCLUSIONS: Our simple visual assessment of CT images can predict the severity of illness, a resulting decrease in respiratory function, and the need for supplemental respiratory ventilation among patients with COVID-19.


Assuntos
COVID-19/classificação , COVID-19/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Amidas/uso terapêutico , Antivirais/uso terapêutico , Temperatura Corporal , Proteína C-Reativa/metabolismo , COVID-19/tratamento farmacológico , COVID-19/fisiopatologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , L-Lactato Desidrogenase/sangue , Pulmão/diagnóstico por imagem , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Mucina-1/sangue , Neutrófilos , Valor Preditivo dos Testes , Prognóstico , Pirazinas/uso terapêutico , Interpretação de Imagem Radiográfica Assistida por Computador , Estudos Retrospectivos , SARS-CoV-2 , Esteroides/uso terapêutico
7.
Crit Care ; 26(1): 1, 2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-34980198

RESUMO

BACKGROUND: SARS-CoV-2 seems to affect the regulation of pulmonary perfusion. Hypoperfusion in areas of well-aerated lung parenchyma results in a ventilation-perfusion mismatch that can be characterized using subtraction computed tomography angiography (sCTA). This study aims to evaluate the efficacy of oral sildenafil in treating COVID-19 inpatients showing perfusion abnormalities in sCTA. METHODS: Triple-blinded, randomized, placebo-controlled trial was conducted in Chile in a tertiary-care hospital able to provide on-site sCTA scans and ventilatory support when needed between August 2020 and March 2021. In total, 82 eligible adults were admitted to the ED with RT-PCR-confirmed or highly probable SARS-COV-2 infection and sCTA performed within 24 h of admission showing perfusion abnormalities in areas of well-aerated lung parenchyma; 42 were excluded and 40 participants were enrolled and randomized (1:1 ratio) once hospitalized. The active intervention group received sildenafil (25 mg orally three times a day for seven days), and the control group received identical placebo capsules in the same way. Primary outcomes were differences in oxygenation parameters measured daily during follow-up (PaO2/FiO2 ratio and A-a gradient). Secondary outcomes included admission to the ICU, requirement of non-invasive ventilation, invasive mechanical ventilation (IMV), and mortality rates. Analysis was performed on an intention-to-treat basis. RESULTS: Totally, 40 participants were enrolled (20 in the placebo group and 20 in the sildenafil group); 33 [82.5%] were male; and median age was 57 [IQR 41-68] years. No significant differences in mean PaO2/FiO2 ratios and A-a gradients were found between groups (repeated-measures ANOVA p = 0.67 and p = 0.69). IMV was required in 4 patients who received placebo and none in the sildenafil arm (logrank p = 0.04). Patients in the sildenafil arm showed a significantly shorter median length of hospital stay than the placebo group (9 IQR 7-12 days vs. 12 IQR 9-21 days, p = 0.04). CONCLUSIONS: No statistically significant differences were found in the oxygenation parameters. Sildenafil treatment could have a potential therapeutic role regarding the need for IMV in COVID-19 patients with specific perfusion patterns in sCTA. A large-scale study is needed to confirm these results. TRIAL REGISTRATION: Sildenafil for treating patients with COVID-19 and perfusion mismatch: a pilot randomized trial, NCT04489446, Registered 28 July 2020, https://clinicaltrials.gov/ct2/show/NCT04489446 .


Assuntos
COVID-19 , Citrato de Sildenafila , Vasodilatadores , Administração Oral , Adulto , Idoso , COVID-19/tratamento farmacológico , COVID-19/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Citrato de Sildenafila/administração & dosagem , Resultado do Tratamento , Vasodilatadores/administração & dosagem , Relação Ventilação-Perfusão
8.
Crit Care ; 26(1): 12, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983597

RESUMO

BACKGROUND: In the context of acute respiratory distress syndrome (ARDS), the response to lung recruitment maneuvers (LRMs) varies considerably from one patient to another and so is difficult to predict. The aim of the study was to determine whether or not the recruitment-to-inflation (R/I) ratio could differentiate between patients according to the change in lung mechanics during the LRM. METHODS: We evaluated the changes in gas exchange and respiratory mechanics induced by a stepwise LRM at a constant driving pressure of 15 cmH2O during pressure-controlled ventilation. We assessed lung recruitability by measuring the R/I ratio. Patients were dichotomized with regard to the median R/I ratio. RESULTS: We included 30 patients with moderate-to-severe ARDS and a median [interquartile range] R/I ratio of 0.62 [0.42-0.83]. After the LRM, patients with high recruitability (R/I ratio ≥ 0.62) presented an improvement in the PaO2/FiO2 ratio, due to significant increase in respiratory system compliance (33 [27-42] vs. 42 [35-60] mL/cmH2O; p < 0.001). In low recruitability patients (R/I < 0.62), the increase in PaO2/FiO2 ratio was associated with a significant decrease in pulse pressure as a surrogate of cardiac output (70 [55-85] vs. 50 [51-67] mmHg; p = 0.01) but not with a significant change in respiratory system compliance (33 [24-47] vs. 35 [25-47] mL/cmH2O; p = 0.74). CONCLUSION: After the LRM, patients with high recruitability presented a significant increase in respiratory system compliance (indicating a gain in ventilated area), while those with low recruitability presented a decrease in pulse pressure suggesting a drop in cardiac output and therefore in intrapulmonary shunt.


Assuntos
COVID-19 , Pulmão , Síndrome do Desconforto Respiratório , COVID-19/complicações , Humanos , Pulmão/fisiopatologia , Respiração com Pressão Positiva , Síndrome do Desconforto Respiratório/terapia , Síndrome do Desconforto Respiratório/virologia , SARS-CoV-2
9.
PLoS One ; 17(1): e0262193, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34986168

RESUMO

OBJECTIVE: To prospectively evaluate a logistic regression-based machine learning (ML) prognostic algorithm implemented in real-time as a clinical decision support (CDS) system for symptomatic persons under investigation (PUI) for Coronavirus disease 2019 (COVID-19) in the emergency department (ED). METHODS: We developed in a 12-hospital system a model using training and validation followed by a real-time assessment. The LASSO guided feature selection included demographics, comorbidities, home medications, vital signs. We constructed a logistic regression-based ML algorithm to predict "severe" COVID-19, defined as patients requiring intensive care unit (ICU) admission, invasive mechanical ventilation, or died in or out-of-hospital. Training data included 1,469 adult patients who tested positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) within 14 days of acute care. We performed: 1) temporal validation in 414 SARS-CoV-2 positive patients, 2) validation in a PUI set of 13,271 patients with symptomatic SARS-CoV-2 test during an acute care visit, and 3) real-time validation in 2,174 ED patients with PUI test or positive SARS-CoV-2 result. Subgroup analysis was conducted across race and gender to ensure equity in performance. RESULTS: The algorithm performed well on pre-implementation validations for predicting COVID-19 severity: 1) the temporal validation had an area under the receiver operating characteristic (AUROC) of 0.87 (95%-CI: 0.83, 0.91); 2) validation in the PUI population had an AUROC of 0.82 (95%-CI: 0.81, 0.83). The ED CDS system performed well in real-time with an AUROC of 0.85 (95%-CI, 0.83, 0.87). Zero patients in the lowest quintile developed "severe" COVID-19. Patients in the highest quintile developed "severe" COVID-19 in 33.2% of cases. The models performed without significant differences between genders and among race/ethnicities (all p-values > 0.05). CONCLUSION: A logistic regression model-based ML-enabled CDS can be developed, validated, and implemented with high performance across multiple hospitals while being equitable and maintaining performance in real-time validation.


Assuntos
COVID-19/diagnóstico , Sistemas de Apoio a Decisões Clínicas , Modelos Logísticos , Aprendizado de Máquina , Triagem/métodos , COVID-19/fisiopatologia , Serviço Hospitalar de Emergência , Humanos , Curva ROC , Índice de Gravidade de Doença
10.
Anticancer Res ; 42(1): 397-405, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34969750

RESUMO

BACKGROUND/AIM: Cancer cachexia encompasses several deleterious physiological alterations associated with functional impairments, poor quality of life, and increased mortality. The aim of this study was to examine the effects of chronic moderate intensity exercise training on markers of cachexia. MATERIALS AND METHODS: Balb/c mice were randomly assigned to sedentary (SED) or exercise (EX) groups and EX mice were further randomly assigned to one of three exercise modalities (aerobic, resistance, combined). RESULTS: Cachexia was induced in SED animals inoculated with C26 cells, as evidenced by significant changes in numerous markers. All cachexia-related perturbations were significantly attenuated in EX versus SED animals. Systemic inflammation was significantly decreased in all EX groups, as evident by a normalization of spleen mass and plasma IL-6. CONCLUSION: Multiple moderate intensity exercise modalities can provide significant benefits in cachectic mice, and this may be due, at least in part, to decreased systemic inflammation.


Assuntos
Caquexia/terapia , Exercício Físico/fisiologia , Neoplasias/terapia , Condicionamento Físico Animal , Animais , Caquexia/etiologia , Caquexia/fisiopatologia , Modelos Animais de Doenças , Humanos , Camundongos , Músculo Esquelético/fisiologia , Neoplasias/complicações , Neoplasias/fisiopatologia , Modalidades de Fisioterapia , Qualidade de Vida , Treinamento de Força , Comportamento Sedentário
11.
Gene ; 808: 145989, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34624458

RESUMO

SERPINB5 is a mammary serine protease inhibitor, which is involved in various cellular functions. The aberrant expression of SERPINB5 is reported in many cancers along with GBC but limited information is available about its role in genetic predisposition for GBC. We carried out case-control study in 206 cases and 219 controls. Promoter SNPs were genotyped by Sanger's sequencing. In-silico promoter analysis and luciferase reporter assay were done to elucidate the role of promoter variants in regulation of SERPINB5 expression. Out of four SNPs, three SERPINB5 promoter variants showed association with GBC in different models. The 'C' allele of variant rs17071138 was found to be significantly associated with GBC (p = 0.017). The 'T' allele of rs3744940 significantly increased the risk for GBC in dominant (p = 0.035) and additive models (p = 0.005). Also, rs3744941 'T' allele increased the risk for GBC by dominant (p = 0.042) as well as additive models (p = 0.016). In-silico promoter analysis and luciferase reporter assay revealed the probable regulatory role of the SERPINB5 promoter variant rs17071138 on the expression. Overall, our study reveals the genetic association of SERPINB5 promoter variants with GBC and possible role of rs17071138 in the regulation of expression.


Assuntos
Neoplasias da Vesícula Biliar/genética , Regulação da Expressão Gênica/genética , Serpinas/genética , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Neoplasias da Vesícula Biliar/metabolismo , Neoplasias da Vesícula Biliar/fisiopatologia , Expressão Gênica/genética , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Genótipo , Haplótipos/genética , Humanos , Índia , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética , Sequências Reguladoras de Ácido Nucleico/genética , Serpinas/fisiologia
12.
Surg Clin North Am ; 102(1): 117-137, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34800381

RESUMO

Patients with cirrhosis account for 3% of intensive care unit admissions with hospital mortality exceeding 50%; however, improvements in survival among patients with acutely decompensated cirrhosis and organ failure have been described when treated in specialized liver transplant centers. Acute-on-chronic liver failure is a distinct clinical syndrome characterized by decompensated cirrhosis associated with one or more organ failures resulting in a significantly higher short-term mortality. In this review, we will discuss the management of common life-threatening complications in the patient with cirrhosis that require intensive care management including neurologic, cardiovascular, gastrointestinal, pulmonary, and renal complications.


Assuntos
Insuficiência Hepática Crônica Agudizada/terapia , Cuidados Críticos/métodos , Encefalopatia Hepática/terapia , Síndrome Hepatopulmonar/terapia , Síndrome Hepatorrenal/terapia , Hipertensão Pulmonar/terapia , Cirrose Hepática/terapia , Insuficiência Hepática Crônica Agudizada/etiologia , Terapia Combinada , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/terapia , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia , Encefalopatia Hepática/etiologia , Síndrome Hepatopulmonar/etiologia , Síndrome Hepatorrenal/etiologia , Humanos , Hipertensão Pulmonar/etiologia , Cirrose Hepática/fisiopatologia , Transplante de Fígado
13.
Surg Clin North Am ; 102(1): 85-104, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34800391

RESUMO

Patients with heart failure, including those with implanted left ventricular assist devices, continue to increase in number. When they require noncardiac surgery, cardiac critical care expertise may not be immediately available to assist. This review serves to provide surgeons and surgical intensivists with a brief overview of the management of this patient population and common clinical scenarios and complications.


Assuntos
Cuidados Críticos/métodos , Insuficiência Cardíaca/cirurgia , Coração Auxiliar , Assistência Perioperatória/métodos , Anticoagulantes/uso terapêutico , Fármacos Cardiovasculares/uso terapêutico , Terapia Combinada , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Coração Auxiliar/efeitos adversos , Monitorização Hemodinâmica , Humanos , Assistência Perioperatória/instrumentação
14.
J Sci Food Agric ; 102(1): 434-444, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34143895

RESUMO

BACKGROUND: The incidence of inflammatory bowel disease (IBD) continues to increase worldwide. Multiple factors, including diet, loss of the intestinal barrier function, and imbalance of the immune system can cause IBD. A balanced diet is important for maintaining a healthy bowel and preventing IBD from occurring. The effects of probiotic Lactobacillus gasseri-fermented Maillard reaction products (MRPs) prepared by reacting whey protein with galactose on anti-inflammation and intestinal homeostasis were investigated in this study, which compared MPRs and probiotics separately. RESULTS: In an animal colitis model induced by 2% dextran sulfate sodium (DSS), FWG administration alleviated colon length loss and maintained intestinal immune system homeostasis as reflected by down-regulated interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α output, and metallopeptidase-9, and epithelial barrier balance as reflected by up-regulated occludin, E-cadherin, and zonula occludens-1 production in the colon. Furthermore, the expression of splenic cytokines such as IL-6, TNF-α, and IL-10 was up-regulated in the FWG-treated mice in a comparable amount to the control group to ensure the balance of immune responses. CONCLUSION: This study showed that the use of FWG protects the intestines from colitis caused by DSS and maintains immune balance. FWG increased antioxidant enzyme activity, increased intestinal permeability, and regulated the balance of pro- and anti-inflammatory cytokines in the intestines and spleen. Continued intake of FWG can alleviate IBD symptoms through the preservation of mucosal immune responses, epithelial junction and homeostasis through the regulated splenic cytokines. © 2021 Society of Chemical Industry.


Assuntos
Colite/tratamento farmacológico , Produtos Finais de Glicação Avançada/administração & dosagem , Lactobacillus gasseri/metabolismo , Probióticos/administração & dosagem , Animais , Anti-Inflamatórios/administração & dosagem , Colite/induzido quimicamente , Colite/imunologia , Colite/fisiopatologia , Colo/efeitos dos fármacos , Colo/imunologia , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Galactose/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Homeostase/efeitos dos fármacos , Humanos , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Junções Íntimas/genética , Junções Íntimas/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Proteínas do Soro do Leite/metabolismo
15.
Endocrinology ; 163(2)2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34940833

RESUMO

CONTEXT: Parathyroid hormone (PTH) replacement is a promising approach in the management of hypoparathyroidism but long-acting analogues need to be developed. To date, animal models for testing PTH required parathyroidectomy by surgery. We have developed a nonsurgical rodent hypoparathyroid model and tested a delayed-clearance PTH molecule (DC-PTH). OBJECTIVE: The aim of this study was to use cinacalcet to suppress calcium levels in normal rats and to reverse these effects with the administration of PTH or PTH analogues. METHODS: Male Wistar rats were gavaged with either 30 mg/kg cinacalcet-HCl (cinacalcet) or vehicle only. Animals were then dosed with either single or repeated subcutaneous doses of PTH 1-34 or a DC-PTH at 20 nmol/kg. Control animals received vehicle only. Serum samples were analyzed for ionized calcium (iCa), phosphate, PTH, and DC-PTH. A pharmacokinetic-pharmacodynamic (PK-PD) model was built for cinacalcet, PTH 1-34, and DC-PTH using Phoenix64. RESULTS: Cinacalcet reduced iCa levels between 2 and 24 hours, returning to baseline by 72 hours post dose with nadir at 8 hours (analysis of variance P < .001), associated with a fall in rat PTH. For phosphate there was a variable biphasic response. Single-dose PTH abrogated the cinacalcet-induced fall in iCa for up to 2 hours. DC-PTH prevented the fall in iCa from 4 hours post dose and gave a prolonged response, with iCa levels quicker to return to baseline than controls. DC-PTH has a half-life of 11.5 hours, approximately 44 times longer than human PTH 1-34. The PK-PD models defined the reproducible effect of cinacalcet on iCa and that DC-PTH had prolonged biological activity. CONCLUSION: The administration of cinacalcet provides a robust and reproducible nonsurgical animal model of hypoparathyroidism. DC-PTH holds promise for the treatment of hypoparathyroidism in the future.


Assuntos
Cinacalcete/farmacologia , Hipoparatireoidismo/fisiopatologia , Hormônio Paratireóideo/sangue , Animais , Células CHO , Cálcio/química , Cálcio/metabolismo , Cricetulus , Modelos Animais de Doenças , Masculino , Glândulas Paratireoides/fisiopatologia , Hormônio Paratireóideo/química , Paratireoidectomia , Fosfatos/química , Ratos , Ratos Wistar , Resultado do Tratamento
16.
Biochim Biophys Acta Gen Subj ; 1866(1): 130010, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34525397

RESUMO

BACKGROUND: Humanin is an endogenous mitochondria-derived peptide that plays critical roles in oxidative stress, inflammation and CAD. In this study, we measured the levels of circulating humanin, markers of oxidative stress and inflammation in patients with unstable angina and MI and studied the relationship between these parameters and major adverse cardiac events (MACE). METHODS: A total of 327 subjects were recruited from the inpatient department at First Hospital of Jilin University and divided into 3 groups [control, angina and myocardial infarction (MI)] based on the clinical data and the results of the angiography. Serum humanin and thiobarbituric acid reactive substances (TBARS) were measured at the time of initial admission. The hospitalization data and MACE of all patients were collected. RESULTS: Circulating humanin levels were lower in the angina group compared to controls [124.22 ±â€¯63.02 vs. 157.77 ±â€¯99.93 pg/ml, p < 0.05] and even lower in MI patients [67.17 ±â€¯24.35 pg/ml, p < 0.05 vs controls] and oxidative stress marker were higher in MI patients compared to the control and angina groups [12.94 ±â€¯4.55 vs. 8.26 ±â€¯1.66 vs. 9.06 ±â€¯2.47 umol/ml, p < 0.05]. Lower circulating humanin levels was an independent risk factor of MI patients. Circulating humanin levels could be used to predict MACE in angina group. CONCLUSIONS: Lower circulating humanin levels was an independent risk factor for CAD, and a potential prognostic marker for mild CAD. GENERAL SIGNIFICANCE: Humanin may become a new index for the diagnosis and treatment of CAD.


Assuntos
Doença da Artéria Coronariana/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/análise , Adulto , Angina Pectoris/metabolismo , Angina Pectoris/fisiopatologia , Biomarcadores/sangue , Doença da Artéria Coronariana/sangue , Feminino , Coração , Humanos , Inflamação/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/sangue , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Pessoa de Meia-Idade , Mitocôndrias , Infarto do Miocárdio/metabolismo , Estresse Oxidativo/fisiologia , Prognóstico , Fatores de Risco
17.
Br J Radiol ; 95(1129): 20210311, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34618546

RESUMO

Primary aldosteronism (PA) is the primary cause of secondary hypertension. The prevalence of PA has probably been underestimated in the past and recent studies suggest that PA could be present in up to 10% of patients suffering from hypertension. Aldosterone excess in PA can be caused by unilateral adrenal disease, usually adrenal adenoma, or bilateral adrenal hyperplasia. Differentiation between unilateral and bilateral disease is clinically important as the former can effectively be treated by removal of the affected adrenal. CT or MRI cannot reliably distinguish unilateral from bilateral disease. Therefore, adrenal vein sampling (AVS) is an important step of the diagnostic work-up in patients with PA. Current guidelines recommend PA in virtually all patients with biochemically diagnosed PA who would undergo adrenal surgery if unilateral PA was diagnosed. In this narrative review, we give an overview of the current technique used for AVS with a focus on the experience with this technique at the University Hospital Basel, Switzerland.


Assuntos
Glândulas Suprarrenais/irrigação sanguínea , Aldosterona/sangue , Hiperaldosteronismo/diagnóstico , Glândulas Suprarrenais/diagnóstico por imagem , Coleta de Amostras Sanguíneas , Humanos , Hiperaldosteronismo/complicações , Hiperaldosteronismo/diagnóstico por imagem , Hiperaldosteronismo/fisiopatologia , Hipertensão/etiologia , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Veias
18.
Biochim Biophys Acta Gen Subj ; 1866(1): 130022, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34626747

RESUMO

BACKGROUND: The discovery of humanin (HN/MTRNR2) 20 years ago blazed a trail to identifying mitochondrial derived peptides with biological function. SCOPE: Humanin is associated with pro-survival, cytoprotective, anti-inflammatory, and anti-oxidative properties and may play a role in reducing neurodegenerative and metabolic disease progression. Although the role of humanin in vitro and in vivo laboratory models is well characterized, the regulation of humanin in natural models that encounter lethal cytotoxic and oxidative insults, as part of their natural history, require immediate research. In this review, we discuss the conservation of humanin-homologues across champion hibernators, anoxia and freeze-tolerant vertebrates and postulate on the putative roles of humanin in non-model species. SIGNIFICANCE: We hope characterization of humanin in animals that are naturally immune to cellular insults, that are otherwise lethal for non-tolerant species, will elucidate key biomarkers and cytoprotective pathways with therapeutic potential and help differentiate pro-survival mechanisms from cellular consequences of stress.


Assuntos
Hibernação/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Estresse Fisiológico/fisiologia , Animais , Resposta ao Choque Frio/fisiologia , Humanos , Hipóxia/metabolismo , Hipóxia/fisiopatologia , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Fenômenos Fisiológicos do Sistema Nervoso
19.
Life Sci ; 289: 120217, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34896162

RESUMO

AIMS: In patients with colitis, the high comorbidity of depressive disorders is well-known, but the detailed mechanisms remain unresolved. In this study, we examined whether colitis induced by dextran sulfate sodium (DSS) increased the susceptibility to chronic unpredictable mild stress (CUMS) in C57BL/6J mice with resilience to CUMS. MAIN METHODS: To induce experimental colitis and depressive-like behaviors, male 7-weeks old C57BL/6J mice were administered ad libitum 1% DSS solution for 11 days, and subjected to various mild stressors in a chronic, inevitable and unpredictable way according to a random schedule for 21 days, respectively. KEY FINDINGS: In naïve mice exposed to CUMS, their immobility times in a forced swim (FS) test were almost equal to those in control mice. The DSS administration to naïve mice induced colitis without depressive-like behavior, and at 18 days after termination of the DSS administration, the colitis had recovered to control levels, while altered diversity and composition of bacterial genera such as Bacteroides spp., Alistipes spp., etc., were found in the gut microbiota. Exposure of mice with DSS-induced colitis to CUMS (DSS + CUMS) significantly increased the immobility times in the FS test. In the gut microbiota of DSS + CUMS mice, the alteration profile of the relative abundance of bacterial genera differed from in the DSS ones. SIGNIFICANCE: These findings indicate that mice with colitis exhibit increased susceptibility to psychological stress, resulting in induction of depressive-like behavior, and this might be due, at least in part, to altered characteristics of the gut microbiota.


Assuntos
Comportamento Animal/efeitos dos fármacos , Colite , Depressão , Sulfato de Dextrana/toxicidade , Estresse Psicológico , Animais , Colite/induzido quimicamente , Colite/fisiopatologia , Colite/psicologia , Depressão/induzido quimicamente , Depressão/fisiopatologia , Depressão/psicologia , Suscetibilidade a Doenças/induzido quimicamente , Suscetibilidade a Doenças/fisiopatologia , Suscetibilidade a Doenças/psicologia , Masculino , Camundongos , Estresse Psicológico/induzido quimicamente , Estresse Psicológico/fisiopatologia , Estresse Psicológico/psicologia
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