Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 21.003
Filtrar
2.
Medicine (Baltimore) ; 100(30): e26719, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34397705

RESUMO

ABSTRACT: Liver dysfunction in patients with COVID-19 (coronavirus disease 2019) has been described. However, it is not clear if the presence of abnormal liver function tests at presentation was related to underlying undiagnosed liver disease, or a result of the viral infection.We retrospectively examined the first 554 consecutive polymerase chain reaction positive SARS-CoV-2 patients admitted from February 2020 to April 2020 to our academic medical centre. We reviewed their clinical data, chest radiography and laboratory studies obtained within 24 hour of admission.Despite similar hemodynamic parameters, we found significant aspartate transaminase elevation (64 ±â€Š141 vs 35 ±â€Š23 U/L, P < .001) in those with pneumonia compared to those without. Elevated liver enzymes were seen in 102 patients (18.4%). They presented with higher temperatures (38.5 ±â€Š0.9 vs 37.5 ±â€Š0.8 degC, P = .011), higher total white cell counts (6.95 ±â€Š2.29 vs 6.39 ±â€Š2.19 x109/L, P = .021), serum ferritin (240 ±â€Š274 vs 165 ±â€Š198 ng/ml, P = .002) and lactate dehydrogenase (632 ±â€Š912 vs 389 ±â€Š107 U/L, P < .001). These patients were more likely to require intensive care (6.9% vs 2.7% P = .036) and mechanical ventilation (5.9% vs 2.2%, P = .046). Migrant workers from dormitories had a higher rate of baseline liver function test abnormalities (88/425 vs 14/129, P = .01), which were more likely to persist at the time of discharge.Despite relatively mild COVID-19 disease, there was a significant prevalence of liver dysfunction, particularly amongst migrant workers. Elevated liver enzymes were associated with more severe disease, despite similar haemodynamic characteristics. Future studies should explore whether pre-existing liver disease may predispose to more severe COVID-19 disease.


Assuntos
Aspartato Aminotransferases/sangue , COVID-19/complicações , L-Lactato Desidrogenase/sangue , Hepatopatias/etiologia , Adulto , COVID-19/sangue , Feminino , Ferritinas/sangue , Humanos , Contagem de Leucócitos , Hepatopatias/sangue , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Singapura
3.
Molecules ; 26(16)2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34443682

RESUMO

Atherosclerosis is the main cause of cardiovascular diseases which in turn, lead to the highest number of mortalities globally. This pathophysiological condition is developed due to a constant elevated level of plasma cholesterols. Statin is currently the widely used treatment in reducing the level of cholesterols, however, it may cause adverse side effects. Therefore, there is an urgent need to search for new alternative treatment. PCSK9 is an enzyme responsible in directing LDL-receptor (LDL-R)/LDL-cholesterols (LDL-C) complex to lysosomal degradation, preventing the receptor from recycling back to the surface of liver cells. Therefore, PCSK9 offers a potential target to search for small molecule inhibitors which inhibit the function of this enzyme. In this study, a marine invertebrate Acanthaster planci, was used to investigate its potential in inhibiting PCSK9 and lowering the levels of cholesterols. Cytotoxicity activity of A. planci on human liver HepG2 cells was carried out using the MTS assay. It was found that methanolic extract and fractions did not exhibit cytotoxicity effect on HepG2 cell line with IC50 values of more than 30 µg/mL. A compound deoxythymidine also did not exert any cytotoxicity activity with IC50 value of more than 4 µg/mL. Transient transfection and luciferase assay were conducted to determine the effects of A. planci on the transcriptional activity of PCSK9 promoter. Methanolic extract and Fraction 2 (EF2) produced the lowest reduction in PCSK9 promoter activity to 70 and 20% of control at 12.5 and 6.25 µg/mL, respectively. In addition, deoxythymidine also decreased PCSK9 promoter activity to the lowest level of 60% control at 3.13 µM. An in vivo study using Sprague Dawley rats demonstrated that 50 and 100 mg/kg of A. planci methanolic extract reduced the total cholesterols and LDL-C levels to almost similar levels of untreated controls. The level of serum glutamate oxalate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) showed that the administration of the extract did not produce any toxicity effect and cause any damage to rat liver. The results strongly indicate that A. planci produced a significant inhibitory activity on PCSK9 gene expression in HepG2 cells which may be responsible for inducing the uptake of cholesterols by liver, thus, reducing the circulating levels of total cholesterols and LDL-C. Interestingly, A. planci also did show any adverse hepato-cytotoxicity and toxic effects on liver. Thus, this study strongly suggests that A. planci has a vast potential to be further developed as a new class of therapeutic agent in lowering the blood cholesterols and reducing the progression of atherosclerosis.


Assuntos
Colesterol/sangue , Pró-Proteína Convertase 9/antagonistas & inibidores , Estrelas-do-Mar/química , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Morte Celular , Proliferação de Células , LDL-Colesterol/sangue , Células Hep G2 , Humanos , Luciferases/metabolismo , Masculino , Metanol , Regiões Promotoras Genéticas/genética , Pró-Proteína Convertase 9/genética , Pró-Proteína Convertase 9/metabolismo , Ratos Sprague-Dawley , Timidina/farmacologia , Triglicerídeos/sangue
4.
Nutrients ; 13(7)2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34371959

RESUMO

Polycystic ovary syndrome (PCOS) increases type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) with insulin resistance. We hypothesized that a 35 g whey preload would improve insulin sensitivity and glucose handling while reducing biomarkers associated with NAFLD. Twenty-nine age-matched women (CON = 15, PCOS = 14) completed oral glycemic tolerance tests following baseline (Day 0) as well as an acute (Day 1) and short-term whey supplementation (Day 7). Whey had an interaction effect on glucose (p = 0.02) and insulin (p = 0.03), with glucose remaining stable and insulin increasing with whey supplementation. Insulin sensitivity (p < 0.01) improved with whey associated with increased glucagon secretion (p < 0.01). Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) remained unchanged, but "day" had an effect on the AST:ALT ratio (p = 0.04), whereas triglycerides and sex hormone binding globulin overall were greater in the PCOS group (p < 0.05). Total cholesterol decreased in PCOS (by 13%) and CON (by 8%) (NS). HepG2 cells treated with plasma from participants before and after whey decreased lipid accumulation in the PCOS group after whey (p < 0.05). Whey provided an insulinogenic and glycemic homeostatic effect in women with PCOS with the potential to combat NAFLD-consequences.


Assuntos
Glicemia/análise , Suplementos Nutricionais , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/complicações , Proteínas do Soro do Leite/administração & dosagem , Adulto , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Colesterol/sangue , Feminino , Células Hep G2 , Humanos , Insulina/sangue , Resistência à Insulina , Metabolismo dos Lipídeos , Síndrome do Ovário Policístico/metabolismo , Globulina de Ligação a Hormônio Sexual/metabolismo , Triglicerídeos/sangue , Adulto Jovem
5.
Medicine (Baltimore) ; 100(31): e26511, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397794

RESUMO

ABSTRACT: Pain sensitization leading to polyalgia can be observed during infectious diseases. The blood pressure cuff-evoked pain threshold (BPCEPT) has been used in previous studies as a screening tool for fibromyalgia.We aimed to use the BPCEPT as a screening test for detecting pain sensitization in patients suffering from infectious diseases. We also investigated whether specific factors were associated with pain sensitization.We performed a prospective comparative study including all patients of our infectious diseases center in a 1-year period. We created a positive control group of patients suffering from fibromyalgia and a negative control group of "apparently healthy" patients consulting for vaccination.The blood pressure (BP) cuff was inflated until the patient signaled that they experienced pain, and this pressure value was noted.A total of 2355 patients were included. The positive control group had significantly lower values of the BPCEPT than all other groups. Among hospitalized patients with infectious diseases, a low BPCEPT was significantly associated with high temperature (P < .0001), older age (P = .002), being a woman (P = .004), high serum glutamic-oxaloacetic transaminase (P = .007), and high C reactive protein levels (P = .02). Moreover, in multivariate analysis, respiratory infection, meningitis, urinary tract infection, febrile neutropenia, and Q fever were independently associated with a low BPCEPT. A significant negative dynamic correlation between the BPCEPT and temperature was also observed (P < .001).We demonstrated for the first time in a large sample of patients that the BPCEPT method can be used to detect pain susceptibility. We observed a significant dynamic correlation between pain sensitization and temperature. Additionally, pain sensitization was associated with some diseases, suggesting that they trigger pain sensitivity.


Assuntos
Determinação da Pressão Arterial , Temperatura Corporal , Infecções/complicações , Dor/etiologia , Fatores Etários , Aspartato Aminotransferases/sangue , Determinação da Pressão Arterial/efeitos adversos , Proteína C-Reativa/metabolismo , Suscetibilidade a Doenças/diagnóstico , Suscetibilidade a Doenças/microbiologia , Suscetibilidade a Doenças/fisiopatologia , Feminino , Fibromialgia/complicações , Humanos , Infecções/fisiopatologia , Masculino , Pessoa de Meia-Idade , Dor/fisiopatologia , Limiar da Dor , Pressão/efeitos adversos , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais
6.
Medicine (Baltimore) ; 100(31): e26693, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397804

RESUMO

ABSTRACT: Previous studies had shown that an increased aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT ratio) was associated with cardiovascular disease. This study aimed to assess the relationship between AST/ALT ratio and all-cause and cardiovascular mortality in patients with hypertension.By March 31, 2020, a cohort of 14,220 Chinese hypertensive patients was followed up. The end point was all-cause and cardiovascular death. Hazard ratios (HRs) and 95% CIs were calculated for mortality associated with AST/ALT ratio, using Cox proportional hazards models and competing risk model.In an average of 1.7 years of follow-up, 1.39% (n = 198) of patients died, 55.5% (n = 110) of whom from cardiovascular disease. AST/ALT ratio was associated with increased risk of all-cause death (HR:1.37, 95% CI:1.15-1.63) and cardiovascular death (HR:1.32, 95% CI:1.03-1.68) after adjustment for other potential confounders. Compared with low AST/ALT ratio (Tertile 1), high AST/ALT ratio was associated with high cause mortality (Tertile 2: HR:1.35, 95% CI:0.86-2.10; Tertile 3: HR:2.10, 95% CI:1.37-3.21; P for trend <.001). Compared with low AST/ALT ratio (Tertile 1), a statistically significant increased risk of cardiovascular mortality was also observed (Tertile 2: HR:1.27, 95% CI:0.70-2.29; Tertile 3: HR:1.92, 95% CI:1.09-3.37; P for trend <.001). High AST/ALT ratio was also associated with high cardiovascular mortality (Tertile 2: HR:1.27, 95% CI:0.70-2.29; Tertile 3: HR:1.92, 95% CI:1.09-3.37; P for trend <.001).Present study indicated that increased AST/ALT ratio levels were predictive of all-cause and cardiovascular mortality among Chinese hypertensive patients.Trial registration: CHICTR, CHiCTR1800017274. Registered 20 July 2018.


Assuntos
Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Hipertensão/sangue , Hipertensão/mortalidade , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/mortalidade , China/epidemiologia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Sistema de Registros , Fatores de Risco
7.
BMC Infect Dis ; 21(1): 818, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34399709

RESUMO

BACKGROUND: Liver injuries have been reported in patients with coronavirus disease 2019 (COVID-19). This study aimed to investigate the clinical role played by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: In this multicentre, retrospective study, the parameters of liver function tests in COVID-19 inpatients were compared between various time-points in reference to SARS-CoV-2 shedding, and 3 to 7 days before the first detection of viral shedding was regarded as the reference baseline. RESULTS: In total, 70 COVID-19 inpatients were enrolled. Twenty-two (31.4%) patients had a self-medication history after illness. At baseline, 10 (14.3%), 7 (10%), 9 (12.9%), 2 (2.9%), 15 (21.4%), and 4 (5.7%) patients already had abnormal alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), albumin, and total bilirubin (TBIL) values, respectively. ALT and AST abnormal rates and levels did not show any significant dynamic changes during the full period of viral shedding (all p > 0.05). The GGT abnormal rate (p = 0.008) and level (p = 0.033) significantly increased on day 10 of viral shedding. Meanwhile, no simultaneous significant increases in abnormal ALP rates and levels were observed. TBIL abnormal rates and levels significantly increased on days 1 and 5 of viral shedding (all p < 0.05). Albumin abnormal decrease rates increased, and levels decreased consistently from baseline to SARS-CoV-2 clearance day (all p < 0.05). Thirteen (18.6%) patients had chronic liver disease, two of whom died. The ALT and AST abnormal rates and levels did not increase in patients with chronic liver disease during SARS-CoV-2 shedding. CONCLUSIONS: SARS-CoV-2 does not directly lead to elevations in ALT and AST but may result in elevations in GGT and TBIL; albumin decreased extraordinarily even when SARS-CoV-2 shedding ended.


Assuntos
COVID-19/complicações , Fígado/virologia , Adulto , Idoso , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , COVID-19/sangue , COVID-19/epidemiologia , Feminino , Humanos , Fígado/patologia , Testes de Função Hepática/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de Doença
8.
Fish Physiol Biochem ; 47(4): 1243-1255, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34226986

RESUMO

The effects of stocking density on growth performance, serum biochemistry, digestive enzymes, immune response, and muscle quality of largemouth bass (Micropterus salmoides) reared in nine in-pond raceway systems (IPRS, 22.0 m × 5.0 m × 2.0 m) were studied. M. salmoides with initial an body weight of 8.25 ± 0.51 g and body length of 6.99 ± 0.44 cm were reared at an initial stocking density of 90.91 ind./m3 (low stocking density, LSD), 113.63 ind./m3 (middle stocking density, MSD), and 136.36 ind./m3 (high stocking density, HSD) with triplication. After 300 days of culture, MSD recorded the highest final body weight, weight gain, specific growth rate, and yield, but the food conversion ratio in MSD was the lowest. The viscerosomatic index in LSD was significantly higher than other groups. The fish serum reared at HSD showed significantly lower total protein, higher total cholesterol, triglyceride, total bilirubin, glucose content, alanine transaminase, and aspartate transaminase activity. Significantly lower intestinal amylase, lipase, trypsin activities, hepatic superoxide dismutase (SOD) and catalase (CAT) activities, and higher malondialdehyde content were detected in HSD compared to others. The content of crude lipid, saturated fatty acid decreased, and total essential amino acid, delicious amino acid, and polyunsaturated fatty acid increased in muscle with stocking density increase. No significant difference was observed in muscle texture. Profitability analysis indicated the benefit-to-cost ratio varied between 1.10 and 1.68, of which MSD was significantly higher than others. The optimal stocking density for M. salmoides should be 113.63 ind./m3 in an IPRS farm.


Assuntos
Aquicultura/métodos , Bass , Alanina Transaminase/sangue , Aminoácidos/metabolismo , Amilases/metabolismo , Animais , Aspartato Aminotransferases/sangue , Bass/sangue , Bass/crescimento & desenvolvimento , Bass/imunologia , Bass/metabolismo , Catalase/metabolismo , Ácidos Graxos/metabolismo , Proteínas de Peixes/sangue , Imunidade , Intestinos/enzimologia , Lipase/metabolismo , Fígado/metabolismo , Músculos/química , Esteróis/sangue , Superóxido Dismutase/metabolismo , Triglicerídeos/sangue , Tripsina/metabolismo
9.
Nat Commun ; 12(1): 4571, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34315874

RESUMO

Understanding mechanisms of hepatocellular damage may lead to new treatments for liver disease, and genome-wide association studies (GWAS) of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) serum activities have proven useful for investigating liver biology. Here we report 100 loci associating with both enzymes, using GWAS across 411,048 subjects in the UK Biobank. The rare missense variant SLC30A10 Thr95Ile (rs188273166) associates with the largest elevation of both enzymes, and this association replicates in the DiscovEHR study. SLC30A10 excretes manganese from the liver to the bile duct, and rare homozygous loss of function causes the syndrome hypermanganesemia with dystonia-1 (HMNDYT1) which involves cirrhosis. Consistent with hematological symptoms of hypermanganesemia, SLC30A10 Thr95Ile carriers have increased hematocrit and risk of iron deficiency anemia. Carriers also have increased risk of extrahepatic bile duct cancer. These results suggest that genetic variation in SLC30A10 adversely affects more individuals than patients with diagnosed HMNDYT1.


Assuntos
Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Proteínas de Transporte de Cátions/genética , Estudo de Associação Genômica Ampla , Manganês/sangue , Mutação/genética , Proteínas de Transporte de Cátions/metabolismo , Regulação da Expressão Gênica , Ligação Genética , Loci Gênicos , Genoma Humano , Células HeLa , Hematócrito , Heterozigoto , Homeostase , Humanos , Fígado/patologia , Manganês/metabolismo , Anotação de Sequência Molecular , Fenótipo , Reprodutibilidade dos Testes
10.
Nutrients ; 13(6)2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34204359

RESUMO

Scientific evidence supports the role of L-glutamine in improving immune function. This could suggest a possible role of L-glutamine in recovery after intense exercise. To this end, the present report aimed to study if oral L-glutamine supplementation could attenuate muscle damage in a group of players of a mainly eccentric sport discipline such as basketball. Participants (n = 12) were supplemented with 6 g/day of glutamine (G group) or placebo (P group) for 40 days in a crossover study design (20 days with glutamine + 20 days with placebo and vice versa). Blood samples were obtained at the beginning and at the end of each period and markers from exercise-induced muscle damage were determined. The glutamine supplemented group displayed significantly low values of aspartate transaminase, creatine kinase and myoglobin in blood, suggesting less muscle damage compared to the placebo. In addition, adrenocorticotropic hormone levels were lower in the glutamine supplemented group than in the placebo. As a result, the circulating cortisol levels did not increase at the end of the study in the glutamine supplemented group. Altogether, the results indicate that glutamine could help attenuate exercise-induced muscle damage in sport disciplines with predominantly eccentric actions.


Assuntos
Basquetebol , Biomarcadores/sangue , Suplementos Nutricionais , Glutamina/administração & dosagem , Músculo Esquelético/efeitos dos fármacos , Adulto , Aspartato Aminotransferases/sangue , Creatina Quinase/sangue , Diástase Muscular/tratamento farmacológico , Método Duplo-Cego , Exercício Físico/fisiologia , Humanos , Mioglobina , Adulto Jovem
11.
Toxicol Appl Pharmacol ; 426: 115636, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34214573

RESUMO

Paraquat (PQ), an herbicide widely used in agriculture, is considered a highly toxic compound. In hepatocytes, P-glycoprotein (P-gp/Abcb1) is a canalicular transporter involved in PQ extrusion from the cell. Previously, we demonstrated that genistein (GNT) induces P-gp in rat liver. In this study, the protective role of GNT pretreatment towards hepatic damage in a model of acute intoxication with PQ in rats, was investigated. Wistar rats were randomized in 4 groups: Control, GNT (5 mg/kg/day sc, 4 days), PQ (50 mg/kg/day ip, last day) and GNT+ PQ. Hepatic lipoperoxidation (LPO) was evaluated by the thiobarbituric acid reactive substances method. Hepatic levels of 4-hydroxynonenal protein adducts (4-HNEp-add) and glutathione-S-transferase alpha (GSTα) protein expression were evaluated by Western blotting. Hepatic glutathione levels and plasma levels of alanine transaminase (ALT) and aspartate transaminase (AST) were also measured. Biliary excretion of PQ was studied in vivo and in isolated perfused liver. PQ was quantified by HPLC. PQ significantly increased AST and ALT activities, malondialdehyde and 4-HNEp-add levels, whereby pretreatment with GNT ameliorated this effect. PQ biliary excretion remained unchanged after treatments in both experimental models. Hepatic GSTα expression was augmented in GNT group. GNT pretreatment increased hepatic glutathione levels in PQ + GNT group. These results agree with the lower content of 4-HNEp-adds in GNT + PQ group respect to PQ group. Unexpectedly, increased activity of P-gp did not enhance PQ biliary excretion. Thus, GNT protective mechanism is likely through the induction of GSTα which results in increased 4-HNE metabolism before formation of protein adducts.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Genisteína/uso terapêutico , Substâncias Protetoras/uso terapêutico , Alanina Transaminase/sangue , Aldeídos/metabolismo , Animais , Aspartato Aminotransferases/sangue , Bile/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Genisteína/farmacologia , Glutationa/metabolismo , Glutationa Transferase/metabolismo , Herbicidas , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Paraquat , Substâncias Protetoras/farmacologia , Ratos Wistar
12.
Biomed Pharmacother ; 140: 111732, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34130201

RESUMO

Nerol, a monoterpene is evident to possess diverse biological activities, including antioxidant, anti-microbial, anti-spasmodic, anthelmintic, and anti-arrhythmias. This study aims to evaluate its hepatoprotective effect against paracetamol-induced liver toxicity in a rat model. Five groups of rats (n = 7) were orally treated (once daily) with 0.05% tween 80 dissolved in 0.9% NaCl solution (vehicle), paracetamol 640 mg/kg (negative control), 50 mg/kg silymarin (positive control), or nerol (50 and 100 mg/kg) for 14 days, followed by the hepatotoxicity induction using paracetamol (PCM). The blood samples and livers of the animals were collected and subjected to biochemical and microscopical analysis. The histological findings suggest that paracetamol caused lymphocyte infiltration and marked necrosis, whereas maintenance of the normal hepatic structural was observed in group pre-treated with silymarin and nerol. The rats pre-treated with nerol significantly and dose-dependently reduced the hepatotoxic markers in animals. Nerol at 100 mg/kg significantly reversed the paracetamol-induced altered situations, including the liver enzymes, plasma proteins, antioxidant enzymes and serum bilirubin, lipid peroxidation (LPO) and cholesterol [e.g., total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c)] levels in animals. Taken together, nerol exerted significant hepatoprotective activity in rats in a dose-dependent manner. PCM-induced toxicity and nerol induced hepatoprotective effects based on expression of inflammatory and apoptosis factors will be future line of work for establishing the precise mechanism of action of nerol in Wistar albino rats.


Assuntos
Acetaminofen , Monoterpenos Acíclicos/uso terapêutico , Analgésicos não Narcóticos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Monoterpenos Acíclicos/farmacologia , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Catalase/sangue , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/patologia , Globulinas/análise , Glutationa/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Substâncias Protetoras/farmacologia , Ratos Sprague-Dawley , Ratos Wistar , Albumina Sérica/análise , Superóxido Dismutase/sangue , gama-Glutamiltransferase/sangue
13.
Cancer Radiother ; 25(5): 469-475, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34120853

RESUMO

PURPOSE: In patients with right-sided breast cancer (BC) the liver might be partially irradiated during adjuvant radiotherapy (RT). Thus, we performed a prospective observational study to evaluate the dose delivered to the liver, and its potential biological impact. PATIENTS AND METHODS: We enrolled 34 patients with right-sided BC treated with adjuvant RT. The RT schedules were either the Canadian (42.5Gy in 16 fx) or standard fractionated (50Gy in 25 fx) regimen respectively with 9 (26.5%) and 25 (73.5%) patients each, ± a boost of 10-16Gy. Each patient had a complete blood count and liver enzymes analysis, before starting and during the last week of treatment. RESULTS: A significant decrease in white blood cells and thrombocytes counts was observed during RT. We observed a significant correlation between certain hepatic parameters and the volume of the irradiated liver and/or the mean liver dose. A significant correlation between the volume of the right lung and the liver mean dose was found (P=0.008). In the bivariate analysis, a significant correlation between fatigue and the white blood cell count's evolution was observed (P<0.025). CONCLUSION: With the standard RT technique, incidental irradiation of the liver was documented in a large number of patients, and some significant hepatic parameters alterations were observed, without an apparent clinical impact, but this study cannot exclude them. The liver mean dose was correlated with the right lung volume suggesting that deep inspiration breath hold (DIBH) techniques may represent a way to decrease the liver dose. These findings need to be evaluated in further larger studies.


Assuntos
Fígado/efeitos da radiação , Neoplasias Unilaterais da Mama/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Fracionamento da Dose de Radiação , Fadiga/etiologia , Feminino , Humanos , Leucopenia/etiologia , Pulmão/efeitos da radiação , Pessoa de Meia-Idade , Órgãos em Risco , Estudos Prospectivos , Dosagem Radioterapêutica , Radioterapia Adjuvante , Trombocitopenia/etiologia
14.
Molecules ; 26(9)2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-34063148

RESUMO

This study aimed to evaluate the cancer chemopreventive activity of vanillic acid (VA) in diethylnitrosamine- and 1,2-dimethylhydrazine-induced liver and colon carcinogenesis in rats. VA did not induce the formation of hepatic glutathione S-transferase placental form (GST-P) positive foci and colonic aberrant crypt foci, demonstrating no carcinogenic activity. VA (75 mg kg-1 body weight) could significantly reduce the number and areas of hepatic GST-P positive foci when administered before carcinogen injections, but no such effect was seen when it was administered after carcinogen injection. No protection was seen in the colon when VA was treated before or after carcinogen injection. Immunohistochemical studies demonstrated the decreased expression of proliferating cell nuclear antigen and the induction of apoptosis. Mechanistic studies showed that VA significantly induced the expression of GSTA-5 and Nrf-2 genes, which are associated with the detoxification system. Likewise, the antiproliferative effect was noticed by the reduction of Cyclin D1 expression. The apoptotic activity may be due to the upregulation of Caspase-3 and Bad levels and downregulation of the Bcl-2 level. These data suggest that VA exhibited significant protection against diethylnitrosamine- and 1,2-dimethylhydrazine-induced hepatocarcinogenesis, which might be related to the induction of the detoxifying enzyme, the reduction of proliferation and the induction of apoptosis.


Assuntos
Carcinogênese/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Substâncias Protetoras/uso terapêutico , Ácido Vanílico/uso terapêutico , 1,2-Dimetilidrazina , Alanina Transaminase/sangue , Animais , Apoptose/efeitos dos fármacos , Aspartato Aminotransferases/sangue , Carcinogênese/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Dietilnitrosamina , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/genética , Masculino , Tamanho do Órgão/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Ratos Wistar , Ácido Vanílico/química , Ácido Vanílico/farmacologia
15.
Life Sci ; 277: 119584, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33961853

RESUMO

AIMS: Ferulic acid (FA) is a component found in plants that has free radical scavenging and liver-protective properties. Acute liver injury (ALI) is a serious complication of sepsis and is closely associated with changes in the levels of inflammatory factors. This study was taken to examine the role of FA in cecal ligation and perforation (CLP)-induced murine ALI and lipopolysaccharide (LPS)-induced cellular ALI models. MATERIALS AND METHODS: An in vivo ALI model was established by performing CLP surgery on C57BL/6 mice. After the ALI model was established, mice were examined for liver injury, including HE staining to observe tissue sections, the percentage of liver/body weight and inflammatory factor levels. Myeloperoxidase (MPO), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were measured in liver or serum using commercial kits. An in vitro ALI model was established using LPS-stimulated RAW264.7 cells. Cell viability was measured by MTT method and the intracellular levels of IL-10, IL-1ß, IL-6, IL-12 and TNF-α inflammatory factors were measured using kits. The expression of GSK-3ß, NF-κB and CREB was measured by western blot or immunofluorescence. KEY FINDINGS: FA pretreatment significantly reduced liver/body weight ratio, decreased MPO, AST and ALT activity, alleviated the inflammatory responses and improved CLP-induced histopathological changes in liver. In addition, in vitro results showed that FA could dose-dependently increase the viability of RAW264.7 cells and decrease the levels of pro-inflammatory factors. SIGNIFICANCE: In conclusion, our data suggest that FA can ameliorate ALI-induced inflammation via the GSK-3ß/NF-κB/CREB pathway, suggesting that FA can be used to protect the liver against ALI.


Assuntos
Ácidos Cumáricos/farmacologia , Sepse/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Ácidos Cumáricos/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Citocinas/metabolismo , Feminino , Glicogênio Sintase Quinase 3 beta/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Células RAW 264.7 , Sepse/complicações , Sepse/metabolismo , Transdução de Sinais
16.
Chem Biol Interact ; 345: 109534, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34051206

RESUMO

Sepsis triggers liver dysfunction with high morbidity and mortality. Here, we elucidated the effect of anemoside B4 on sepsis in cecal ligation and puncture (CLP)-induced mouse model and LPS-induced primary hepatocytes. Following CLP surgery, septic mice were intraperitoneally injected with anemoside B4 (50 or 100 mg/kg). Anemoside B4 improved septic mouse survival rate, decreased serum AST and ALT levels and attenuated liver histopathologic damages. Western blot analysis showed that anemoside B4 elevated the expression of Beclin-1, LC3II/LC3I, Atg3, Atg5, and Atg7, and reduced p62, suggesting the restoration of autophagy flux in liver. More autophagic vesicles were observed in liver after anemoside B4 treatment using transmission electron microscopy. Using ELISA and commercial enzyme kits, we found that anemoside B4 decreased serum TNF-α, IL-6, and IL-1ß levels and increased CAT, SOD and GSH activities. TUNEL staining and western blot revealed that anemoside B4 suppressed cell apoptosis, along with decreased Bax, leaved caspase-3, cleaved PARP, but increased Bcl-2. Consistent with in vivo findings, anemoside B4 inhibited apoptosis, inflammatory response, and oxidative stress and enhanced autophagy in LPS-induced primary hepatocytes. Importantly, these cellular processes were possibly mediated by mTOR/p70S6K signaling, as reflected by the offset of 3-MA in the immunosuppression of anemoside B4.


Assuntos
Autofagia/efeitos dos fármacos , Fígado/lesões , Fígado/patologia , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Saponinas/farmacologia , Sepse/patologia , Serina-Treonina Quinases TOR/metabolismo , Alanina Transaminase/sangue , Animais , Apoptose/efeitos dos fármacos , Aspartato Aminotransferases/sangue , Citoproteção/efeitos dos fármacos , Interleucina-1beta/sangue , Interleucina-6/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/sangue
17.
J Med Virol ; 93(9): 5474-5480, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33963559

RESUMO

In this study, laboratorial parameters of hospitalized novel coronavirus (COVID-19) patients, who were complicated with severe pneumonia, were compared with the findings of cytokine storm developing in macrophage activation syndrome (MAS)/secondary hemophagocytic lymphohistiocytosis (sHLH). Severe pneumonia occurred as a result of cytokine storm in some patients who needed intensive care unit (ICU), and it is aimed to determine the precursive parameters in this situation. Also in this study, the aim is to identify laboratory criteria that predict worsening disease and ICU intensification, as well as the development of cytokine storm. This article comprises a retrospective cohort study of patients admitted to a single institution with COVID-19 pneumonia. This study includes 150 confirmed COVID-19 patients with severe pneumonia. When they were considered as severe pneumonia patients, the clinic and laboratory parameters of this group are compared with H-score criteria. Patients are divided into two subgroups; patients with worsened symptoms who were transferred into tertiary ICU, and patients with stable symptoms followed in the clinic. For the patients with confirmed COVID-19 infection, after they become complicated with severe pneumonia, lymphocytopenia (55.3%), anemia (12.0%), thrombocytopenia (19.3%), hyperferritinemia (72.5%), hyperfibrinogenemia (63.7%) and elevated lactate dehydrogenase (LDH) (90.8%), aspartate aminotransaminase (AST) (31.3%), alanine aminotransaminase (ALT) (20.7%) are detected. There were no significant changes in other parameters. Blood parameters between the pre-ICU period and the ICU period (in which their situation had been worsened and acute respiratory distress syndrome [ARDS] was developed) were also compared. In the latter group lymphocyte levels were found significantly reduced (p = 0.01), and LDH, highly sensitive troponin (hs-troponin), procalcitonin, and triglyceride levels were significantly increased (p < 0.05). In addition, there was no change in hemoglobin, leukocyte, platelet, ferritin, and liver function test levels, including patients who developed ARDS, similar to the cytokine storm developed in MAS/sHLH. COVID-19 pneumonia has similar findings as hyperinflammatory syndromes but does not seem to have typical features as in cytokine storm developed in MAS/sHLH. In the severe patient group who has started to develop ARDS signs, a decrease in lymphocyte level in addition to the elevated LDH, hs-troponin, procalcitonin, and triglyceride levels can be a predictor in progression to ICU admission and could help in the planning of anti-cytokine therapy.


Assuntos
COVID-19/patologia , Síndrome da Liberação de Citocina/patologia , Linfo-Histiocitose Hemofagocítica/patologia , Síndrome de Ativação Macrofágica/patologia , SARS-CoV-2/patogenicidade , Idoso , Alanina Transaminase/sangue , Anemia/sangue , Anemia/diagnóstico , Anemia/imunologia , Anemia/patologia , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/imunologia , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/diagnóstico , Síndrome da Liberação de Citocina/imunologia , Diagnóstico Diferencial , Progressão da Doença , Feminino , Fibrinogênio/metabolismo , Humanos , Hiperferritinemia/sangue , Hiperferritinemia/diagnóstico , Hiperferritinemia/imunologia , Hiperferritinemia/patologia , Unidades de Terapia Intensiva , L-Lactato Desidrogenase/sangue , Linfo-Histiocitose Hemofagocítica/sangue , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/imunologia , Linfopenia/sangue , Linfopenia/diagnóstico , Linfopenia/imunologia , Linfopenia/patologia , Síndrome de Ativação Macrofágica/sangue , Síndrome de Ativação Macrofágica/diagnóstico , Síndrome de Ativação Macrofágica/imunologia , Masculino , Pessoa de Meia-Idade , Pró-Calcitonina/sangue , Estudos Retrospectivos , Trombocitopenia/sangue , Trombocitopenia/diagnóstico , Trombocitopenia/imunologia , Trombocitopenia/patologia , Triglicerídeos/sangue , Troponina/sangue
18.
Environ Toxicol Pharmacol ; 86: 103667, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33933708

RESUMO

Ingestion of perfluorooctanoic acid (PFOA) elicits toxicities in the hepatorenal system. We investigated the effect of PFOA and N-acetylcysteine (NAC) on the hepatorenal function of rats treated thus: control, PFOA (5 mg/kg), NAC (50 mg/kg), PFOA + NAC (5 and 25 mg/kg), and PFOA + NAC (5 and 50 mg/kg). We observed that NAC significantly (p < 0.05) reduced PFOA-induced increase in hepatic and renal function biomarkers of toxicities relative to PFOA alone and alleviated (p < 0.05) decreases in antioxidant status. Increases in oxidative stress and lipid peroxidation in PFOA-treated rats were reverted to normal by NAC and abated increased pro-inflammatory mediators, and decreased anti-inflammatory cytokine both in the hepatorenal system PFOA treated rats. Histology of the kidney and liver indicated that NAC, abated the severity of PFOA-induced damage significantly. Our findings affirm further that oxido-inflammatory mediators involved in PFOA-mediated toxicity can be effectively blocked by NAC through its antioxidant activity.


Assuntos
Acetilcisteína/uso terapêutico , Antioxidantes/uso terapêutico , Caprilatos/toxicidade , Fluorcarbonetos/toxicidade , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Acetilcisteína/farmacologia , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Antioxidantes/farmacologia , Aspartato Aminotransferases/sangue , Creatinina/sangue , Rim/metabolismo , Rim/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Oxirredutases/metabolismo , Ratos Wistar , Ureia/sangue , gama-Glutamiltransferase/sangue
19.
Medicine (Baltimore) ; 100(18): e25819, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33950987

RESUMO

ABSTRACT: Respiratory failure is the major cause of death in patients with coronavirus disease (COVID-19). Data on factors affecting the need for oxygen therapy in early-stage COVID-19 are limited. This study aimed to evaluate the factors associated with the need for oxygen therapy in patients with COVID-19.This is a retrospective study of consecutive COVID-19 patients who were hospitalized between February 27 and June 28, 2020, in South Korea. Logistic regression analyses were performed to identify the factors associated with the need for oxygen therapy.Of the 265 patients included in the study, 26 (9.8%) received oxygen therapy, and 7 of these patients (29.2%) were transferred to a step-up facility, and 3 (11.5%) died. The median age of all patients was 46 years (IQR, 30-60 years), and the median modified early warning score at admission was 1 (IQR, 1-2). In a multivariate logistic regression analysis, being a current smoker (odds ratio [OR] 7.641, 95% confidence interval [CI] 1.686-34.630, P = .008), heart rate (OR 1.053, 95% CI 1.010-1.097, P = .014), aspartate aminotransferase values (OR 1.049, 95% CI 1.008-1.092, P = .020), blood urea nitrogen levels (OR 1.171, 95% CI 1.073-1.278, P < .001), and chest radiographic findings (OR 3.173, 95% CI 1.870-5.382, P < .001) were associated with oxygen therapy.In patients with less severe COVID-19, the need for oxygen therapy is affected by smoking and elevated values of aspartate aminotransferase and blood urea nitrogen. Further research is warranted on the risk factors for deterioration in COVID-19 to efficiently allocate medical resources.


Assuntos
COVID-19/terapia , Oxigenoterapia , Pneumonia Viral/terapia , Adulto , Aspartato Aminotransferases/sangue , Nitrogênio da Ureia Sanguínea , COVID-19/mortalidade , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de Doença , Fumar/efeitos adversos
20.
Med Sci Monit ; 27: e930688, 2021 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-33934098

RESUMO

BACKGROUND Influenza-associated acute necrotizing encephalopathy (IANE) can be lethal and disabling and have a sudden onset and deteriorate rapidly but lacks early diagnostic indicators. We aimed to examine the early clinical diagnostic indicators in children with IANE. MATERIAL AND METHODS Acute influenza patients were grouped according to their clinical manifestations: flu alone (FA), flu with febrile seizure (FS), influenza-associated encephalopathy (IAE), and IANE. The clinical features, biomarkers, neuroelectrophysiological results, and neuroimaging examination results were compared. RESULTS A total of 31 patients were included (FA (n=4), FS (n=8), IAE (n=14), and IANE (n=5)). The IANE group, whose mean age was 3.7 years, was more likely to show rapid-onset seizure, acute disturbance of consciousness (ADOC), Babinski's sign, and death/sequela. More patients in the IANE group required tracheal intubation mechanical ventilation and received intravenous immunoglobulins (IVIG) and glucocorticoids. The alanine aminotransferase (ALT), aspartate transaminase (AST), and lactate dehydrogenase (LDH) levels in the IANE group were significantly higher than in the FS and IAE groups. The aquaporin-4 (AQP-4) antibody and malondialdehyde (MDA) levels in the serum and cerebrospinal fluid (CSF) were notably higher in IANE patients in the acute stage compared with FS and IAE patients. All patients in the IANE group had positive neuroimaging findings. CONCLUSIONS Early clinical warning factors for IANE include rapid-onset seizures in patients under 4 years of age, ADOC, and pathological signs. Increased AQP-4 antibodies and MDA levels in CSF might contribute to early diagnosis. Early magnetic resonance venography (MRV) and susceptibility-weighted imaging (SWI) sequences, or thrombelastography to identify deep vein thrombosis, might indicate clinical deterioration.


Assuntos
Encefalopatias/diagnóstico , Influenza Humana/diagnóstico , Doença Aguda , Alanina Transaminase/sangue , Alanina Transaminase/metabolismo , Aquaporinas/sangue , Aquaporinas/metabolismo , Aspartato Aminotransferases/sangue , Aspartato Aminotransferases/metabolismo , Biomarcadores/sangue , Biomarcadores/metabolismo , Encefalopatias/sangue , Encefalopatias/metabolismo , Líquido Cefalorraquidiano/metabolismo , Pré-Escolar , Feminino , Glucocorticoides/sangue , Glucocorticoides/metabolismo , Humanos , Imunoglobulinas Intravenosas/sangue , Imunoglobulinas Intravenosas/metabolismo , Influenza Humana/sangue , Influenza Humana/metabolismo , L-Lactato Desidrogenase/sangue , L-Lactato Desidrogenase/metabolismo , Masculino , Malondialdeído/sangue , Malondialdeído/metabolismo , Neuroimagem/métodos , Convulsões/sangue , Convulsões/diagnóstico , Convulsões/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...