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2.
BMC Infect Dis ; 21(1): 732, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34340686

RESUMO

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of excessive inflammation. We aimed to describe the clinical and laboratory findings of HLH patients secondary to Visceral leishmaniasis (VL) and their treatment outcome during a 4-year follow-up period compared to primary HLH. METHOD: Forty children with primary HLH confirmed by genetic study and 20 children with HLH secondary to VL confirmed by a blood or bone marrow polymerase chain reaction from 2014 to 2018 in Shiraz, Fars province, Southern Iran, were enrolled. RESULTS: The median age at diagnosis was 11.5 months (range 1-170), and 56.7% were male. Fever and splenomegaly were the most frequent clinical presentations. 93.3% of the subjects had an HScore > 169, which had a good correlation with HLH-2004 criteria (r = 0.371, P = 0.004). Patients with primary HLH experienced more thrombocytopenia (P = 0.012) and higher alanine transaminase (P = 0.016), while patients with VL-associated HLH had higher ferritin (P = 0.034) and erythrocyte sedimentation rate (P = 0.011). Central nervous system (CNS) involvement occurred in 38.3% of patients. The mortality rate was higher in patients with CNS disease (61% vs. 35%, P = 0.051). The 3-yr overall survival rate was 35.9%. (24% in primary HLH and 100% in VL-associated HLH, P < 0.001). In Cox regression analysis, platelet count < 100,000/ µ l (hazard ratio 4.472, 95% confidence interval 1.324-15.107, P = 0.016) correlated with increased mortality in patients with primary HLH. CONCLUSION: VL is a potential source of secondary HLH in regions with high endemicity. Treatment of the underlying disease in VL-associated HLH is sufficient in most cases, with no need to start etoposide-based chemotherapy.


Assuntos
Leishmaniose Visceral/complicações , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/parasitologia , Adolescente , Alanina Transaminase/sangue , Sedimentação Sanguínea , Doenças do Sistema Nervoso Central/complicações , Criança , Pré-Escolar , Feminino , Ferritinas/sangue , Febre , Seguimentos , Humanos , Lactente , Recém-Nascido , Irã (Geográfico) , Linfo-Histiocitose Hemofagocítica/mortalidade , Linfo-Histiocitose Hemofagocítica/terapia , Masculino , Reação em Cadeia da Polimerase , Esplenomegalia/diagnóstico , Taxa de Sobrevida , Trombocitopenia/complicações , Resultado do Tratamento
3.
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
4.
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
5.
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
6.
Eur J Med Res ; 26(1): 92, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34384499

RESUMO

PURPOSE: Herpes zoster (HZ), or shingles, is a clinical syndrome resulting from the reactivation of latent varicella zoster virus (VZV) within the sensory ganglia. We evaluated the safety and tolerability of ES16001 (ethanol extract of Elaeocarpus sylvestris var. ellipticus), a novel inhibitor of varicella zoster virus reactivation in healthy adults. METHOD: Single-center, randomized, double-blind, placebo-controlled, single and multiple ascending dose (SAD and MAD, respectively) studies were conducted in 20- to 45-year-old healthy adults without chronic disease. In the SAD study (n = 32), subjects randomly received a single oral dose of 240, 480, 960, or 1440 mg ES16001 or a placebo. In the MAD study (n = 16), subjects randomly received once daily doses of 480 or 960 mg ES16001 or a placebo for 5 days. The safety and tolerability of the drug were evaluated by monitoring participants' treatment emergent adverse events (TEAEs) and vital signs, electrocardiograms (ECGs), physical examinations, and clinical laboratory tests. RESULTS: In the SAD study, 11 adverse reactions were seen in 5 subjects, and in the MAD study, 8 adverse reactions were seen in 6 subjects. All adverse reactions were mild, and no serious adverse reactions occurred. The most common adverse reaction was an increase in alanine aminotransferase (ALT), but all test values were in the clinically non-significant range, and their clinical significance was judged to be small considering the fact that most of the test values returned to normal immediately after the end of drug administration. CONCLUSION: ES16001 has good safety and tolerability when administered both once and repeatedly to healthy subjects. Further research is needed to identify any possible drug-induced hepatotoxicity, which appears infrequently. Our findings provide a rationale for further clinical investigations of ES16001 for the prevention of HZ. TRIAL REGISTRATION: CRIS, KCT0006066. Registered 7 April 2021-Retrospectively registered, https://cris.nih.go.kr/cris/search/detailSearch.do/19071 ).


Assuntos
Antivirais/efeitos adversos , Elaeocarpaceae/química , Herpes Zoster/tratamento farmacológico , Extratos Vegetais/efeitos adversos , Adulto , Alanina Transaminase/sangue , Antivirais/administração & dosagem , Antivirais/farmacologia , Antivirais/uso terapêutico , Tolerância a Medicamentos , Feminino , Herpes Zoster/prevenção & controle , Humanos , Masculino , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ativação Viral/efeitos dos fármacos
7.
Int J Mol Sci ; 22(14)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34298988

RESUMO

This study evaluated the biocompatibility and biological performance of novel additive-manufactured bioabsorbable iron-based porous suture anchors (iron_SAs). Two types of bioabsorbable iron_SAs, with double- and triple-helical structures (iron_SA_2_helix and iron_SA_3_helix, respectively), were compared with the synthetic polymer-based bioabsorbable suture anchor (polymer_SAs). An in vitro mechanical test, MTT assay, and scanning electron microscope (SEM) analysis were performed. An in vivo animal study was also performed. The three types of suture anchors were randomly implanted in the outer cortex of the lateral femoral condyle. The ultimate in vitro pullout strength of the iron_SA_3_helix group was significantly higher than the iron_SA_2_helix and polymer_SA groups. The MTT assay findings demonstrated no significant cytotoxicity, and the SEM analysis showed cells attachment on implant surface. The ultimate failure load of the iron_SA_3_helix group was significantly higher than that of the polymer_SA group. The micro-CT analysis indicated the iron_SA_3_helix group showed a higher bone volume fraction (BV/TV) after surgery. Moreover, both iron SAs underwent degradation with time. Iron_SAs with triple-helical threads and a porous structure demonstrated better mechanical strength and high biocompatibility after short-term implantation. The combined advantages of the mechanical superiority of the iron metal and the possibility of absorption after implantation make the iron_SA a suitable candidate for further development.


Assuntos
Implantes Absorvíveis , Materiais Biocompatíveis , Âncoras de Sutura , Alanina Transaminase/sangue , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/toxicidade , Fenômenos Biomecânicos , Nitrogênio da Ureia Sanguínea , Fosfatos de Cálcio/química , Fosfatos de Cálcio/toxicidade , Sulfato de Cálcio/administração & dosagem , Sulfato de Cálcio/química , Sulfato de Cálcio/toxicidade , Creatinina/sangue , Desenho de Equipamento , Fêmur/diagnóstico por imagem , Fêmur/ultraestrutura , Ferro , Lasers , Teste de Materiais , Microscopia Eletrônica de Varredura , Estrutura Molecular , Osseointegração , Polímeros/química , Polímeros/toxicidade , Porosidade , Coelhos , Distribuição Aleatória , Resistência à Tração , Vísceras , Microtomografia por Raio-X
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.
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
10.
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
11.
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
12.
Clin Pediatr (Phila) ; 60(8): 370-375, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34100658

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is common in overweight adolescents, and screening with serum alanine transaminase (ALT) levels is recommended by the American Academy of Pediatrics. We sought to determine if ALT is an accurate adolescent screening measure for NAFLD in a nationally representative sample of overweight adolescents. Diagnosis of NAFLD was determined using vibration-controlled transient elastography. Analyses were performed to calculate the sensitivity, specificity, positive predictive value, negative predictive value, and Youden's index at various serum ALT cutoff levels. Receiver operating curves were generated in order to determine ALT's discrimination capability. Males and females were analyzed separately. While average measures (mean and median) of ALT were higher in subjects with NAFLD, ALT provided only minimal discrimination with AUROC (area under the receiver operating characteristic) values of .66 in males and .67 in females. In a nationally representative sample of overweight and obese adolescents, serum ALT level functioned inadequately as a screening test to detect NAFLD.


Assuntos
Alanina Transaminase/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Inquéritos Nutricionais/métodos , Sobrepeso/complicações , Adolescente , Adulto , Biomarcadores/sangue , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Hepatopatia Gordurosa não Alcoólica/complicações , Inquéritos Nutricionais/estatística & dados numéricos , Sobrepeso/sangue , Reprodutibilidade dos Testes , Adulto Jovem
13.
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
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.
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
16.
Med J Aust ; 215(2): 77-82, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34028830

RESUMO

OBJECTIVES: To investigate the prevalence of non-alcoholic fatty liver disease (NAFLD) and its risk factors in regional Victoria. DESIGN: Prospective cross-sectional observational study (sub-study to CrossRoads II health study in Shepparton and Mooroopna). SETTING: Four towns (populations, 6300-49 800) in the Goulburn Valley of Victoria. PARTICIPANTS: Randomly selected from households selected from residential address lists provided by local government organisations for participation in the CrossRoads II study. MAIN OUTCOME MEASURES: Age- and sex-adjusted estimates of NAFLD prevalence, defined by a fatty liver index score of 60 or more in people without excessive alcohol intake or viral hepatitis. RESULTS: A total of 705 invited adults completed all required clinical, laboratory and questionnaire evaluations of alcohol use (participation rate, 37%); 392 were women (56%), and their mean age was 59.1 years (SD, 16.1 years). Of the 705 participants, 274 met the fatty liver index criterion for NAFLD (crude prevalence, 38.9%; age- and sex-standardised prevalence, 35.7%). The mean age of participants with NAFLD (61 years; SD, 15 years) was higher than for those without NAFLD (58 years; SD, 16 years); a larger proportion of people with NAFLD were men (50% v 41%). Metabolic risk factors more frequent among participants with NAFLD included obesity (69% v 15%), hypertension (66% v 48%), diabetes (19% v 8%), and dyslipidaemia (63% v 33%). Mean serum alanine aminotransferase levels were higher (29 U/L; SD, 17 U/L v 24 U/L; SD, 14 U/L) and mean median liver stiffness greater (6.5 kPa; SD, 5.6 kPa v 5.3kPa; SD, 2.0 kPa) in participants with NAFLD. CONCLUSION: The prevalence of NAFLD among adults in regional Victoria is high. Metabolic risk factors are more common among people with NAFLD, as are elevated markers of liver injury.


Assuntos
Hepatopatia Gordurosa não Alcoólica/epidemiologia , Adulto , Idoso , Alanina Transaminase/sangue , Estudos Transversais , Diabetes Mellitus/epidemiologia , Dislipidemias/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Fígado/diagnóstico por imagem , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade/epidemiologia , Prevalência , Estudos Prospectivos , Fatores de Risco , Vitória/epidemiologia
17.
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
18.
Chem Biol Interact ; 345: 109521, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34052195

RESUMO

2,3,7,8-Tetrachlorodibenzo-p-dioxin (dioxin; TCDD) is an environmental contaminant that elicits a variety of toxic effects, many of which are mediated through activation of the aryl hydrocarbon receptor (AhR). Interaction between AhR and the peroxisome proliferator-activated receptor-alpha (PPAR-α), which regulates fatty acid metabolism, has been suggested. Furthermore, with recognition of the prevalence of inflammatory conditions, there is current interest in the potential for inflammatory stress to modulate the response to environmental agents. The aim of this work was to assess the interaction of TCDD with hepatic inflammation modulated by fenofibrate, a PPAR-α agonist. Female, C57BL/6 mice were treated orally with vehicle or fenofibrate (250 mg/kg) for 13 days, and then were given vehicle or 30 µg/kg TCDD. Four days later, the animals received an i.p. injection of lipopolysaccharide-galactosamine (LPS-GalN) (0.05x107 EU/kg and 500 mg/kg, respectively) to incite inflammation, or saline as vehicle control. After 4 h, the mice were euthanized, and blood and liver samples were collected for analysis. Livers of animals treated with TCDD with or without LPS-GalN had increased lipid deposition, and this effect was blocked by fenofibrate. In TCDD/LPS-GalN-treated mice, fenofibrate caused an increase in plasma activity of alanine aminotransferase, a marker of hepatocellular injury. TCDD reduced LPS-GalN-induced apoptosis, an effect that was prevented by fenofibrate pretreatment. LPS-GalN induced an increase in the concentration of interleukin-6 in plasma and accumulation of neutrophils in liver. TCDD exposure enhanced the former response and inhibited the latter one. These results suggest that fenofibrate counteracts the changes in lipid metabolism induced by TCDD but increases inflammation and liver injury in this model of inflammation-TCDD interaction.


Assuntos
Dioxinas/toxicidade , Fígado Gorduroso/tratamento farmacológico , Fenofibrato/farmacologia , PPAR alfa/agonistas , Alanina Transaminase/sangue , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Interações Medicamentosas , Fígado Gorduroso/sangue , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Feminino , Fenofibrato/uso terapêutico , Interleucina-6/sangue , Camundongos , Camundongos Endogâmicos C57BL
19.
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
20.
Prim Care Diabetes ; 15(4): 713-718, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34006475

RESUMO

AIM: This study aimed at providing evidence to consider sex differences in interpretations of laboratory parameters of severe COVID-19 patients with diabetes. METHODS: For 118 diabetic patients, laboratory measurements and clinical outcomes were compared between males and females. This study also compared inflammatory ratios obtained from combinations of six inflammatory markers between the two groups. The risk factors for mortality were identified through logistic regression. RESULTS: Males were 54 (45.8%) and females were 64 (54.2%). Males showed a significant increase in ALT (P = 0.003), CRP (P = 0.03), mean platelet volume (MPV)-to-lymphocyte ratio (P = 0.001), and C-reactive protein-to-albumin ratio (P = 0.044), whereas females had a significant increase in lymphocytes (P < 0.005) and MPV (P = 0.01). In all participants, multivariate analysis illustrated that older age, male sex, increased serum total bilirubin, and decreased PO2 were significant independent predictors of mortality (P < 0.05). CONCLUSION: In severe COVID-19 patients with diabetes, there were significant sex differences in many laboratory characteristics with a higher risk of mortality among males.


Assuntos
Biomarcadores/sangue , COVID-19/diagnóstico , Diabetes Mellitus/diagnóstico , Disparidades nos Níveis de Saúde , Fatores Etários , Idoso , Alanina Transaminase/sangue , Bilirrubina/sangue , Proteína C-Reativa/análise , COVID-19/sangue , COVID-19/mortalidade , Diabetes Mellitus/sangue , Diabetes Mellitus/mortalidade , Feminino , Humanos , Contagem de Linfócitos , Linfócitos/metabolismo , Masculino , Volume Plaquetário Médio , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais
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