Comparative plasma biochemistry analyte data in nesting leatherback (Dermochelys coriacea), foraging green (Chelonia mydas) and foraging and nesting hawksbill (Eretmochelys imbricata) sea turtles in Grenada, West Indies.

Blood biochemistry represents a minimally invasive tool for monitoring sea turtle health, assessing injured sea turtles and supporting conservation strategies. In Grenada, West Indies, plasma biochemical variables were examined in 33 nesting leatherback (Dermochelys coriacea), 49 foraging green (Chelonia mydas), 49 foraging hawksbill (Eretmochelys imbricata) and 12 nesting hawksbill sea turtles sampled between 2017 and 2022. Plasma biochemistry reference intervals are described herein except for nesting hawksbills, which are represented by descriptive statistics due to the low sample size. Select analyte concentrations were positively correlated with curved carapace length in leatherbacks (chloride), green turtles (total protein, albumin and globulin) and foraging hawksbills (total protein, albumin and phosphorus). Cholesterol (7.8 mmol/l ± 1.6 SD) and triglyceride (6.9 mmol/l ± 1.9 SD) concentrations were significantly higher in leatherbacks compared to foraging green turtles, foraging hawksbills and nesting hawksbills (P < 0.001 for all). Cholesterol was significantly higher in nesting hawksbills compared to foraging green turtles (P = 0.050) and foraging hawksbills (P = 0.050). Foraging hawksbills demonstrated significantly higher aspartate transaminase activities than leatherbacks (P = 0.002), green turtles (P = 0.009) and nesting hawksbills (P < 0.001). Biochemical results provide baseline population health data and support guidance for treatments during clinical sea turtle rehabilitation efforts. They also provide insight into species-specific physiologic differences and preludes further studies to better characterize the impacts of life-stage class on biochemistry reference intervals to better support wild sea turtle populations in Grenada.

Association between maternal obesity, essential fatty acids and biomarkers of fetal liver function.

Maternal obesity and the imbalance in linoleic acid (C18:2 n-6, LA) and alpha-linolenic acid (C18:3 n-3, ALA) levels are related with hepatic disturbances in the offspring. However, whether these alterations are present during fetal life is not well understood. Obese and normal weight pregnant women were recruited to determine fatty acids (FAs) consumption, FAs profile (in maternal erythrocytes, placenta and neonatal very low-density lipoproteins VLDL) and biomarkers of fetal liver function, such as gamma-glutamyl transferase (GGT), alpha-fetoprotein (AFP) and albumin, in umbilical cord blood. Stearic acid (C18:0, ST) was lower, and total n-3 FAs tended to be lower in umbilical cord VLDLs of obese women compared to controls. Independently of maternal obesity, GGT levels in umbilical cord blood was positively correlated with the LA content and negatively correlated with the ALA content in maternal erythrocytes. We conclude that maternal obesity and its imbalance of LA and ALA are associated with changes in biomarkers of fetal liver function.

Evaluation of kidney injury through early markers in canine pyometra / Avaliação de lesão renal através de marcadores precoce em piometra canina

Fourteen female dogs diagnosed with pyometra were studied at three separate times: at diagnosis (T0) and 24 h (T1) and 10-15 days (T2) after ovariohysterectomy (OH). The means of the markers, symmetric dimethylarginine (SDMA) (17.71 to 26.54 µg/dL) and the urinary gamma-glutamyl transferase to creatinine ratio (uGGT/uCr) (1.06 to 2.62 U/mg), varied, showing an increase with time. Further, the elevation of gamma-glutamyl transferase (uGGT) (56.61 to 128.12 U/L) and the urinary protein to creatinine ratio (RPC) (0.26 to 1.24) was evident at T0 and T1. A reduction in the means of RPC, uGGT, and uGGT/uCr was observed 10-15 days after OH. Despite the elevation of these markers, the concentration of creatinine (1.11 to 1.40 mg/dL), urea (40.07 to 67.16 mg/dL), and urinary specific gravity (1.027 to 1.028) only presented slight variation. In canine pyometra, complications secondary to acute renal injury may be present that may be mild and transient in most treated animals. As elevation in SDMA and RPC preceded changes in creatinine levels for the evaluation of glomerular filtration, tubular markers could assist in the early identification of renal damage in canine pyometra.(AU)

Catorze cadelas com diagnóstico de piometra foram estudadas em três tempos distintos, sendo no momento do diagnóstico (T0), 24 horas (T1) e 10 a 15 dias (T2) após a ovário-histerectomia (OH). O objetivo foi avaliar o uso de diferentes biomarcadores renais em cadelas com piometra e estimar suas precocidades diante do agravo. As médias em dimetilarginina simétrica (SDMA) (17,71 a 26,54µg/dL) e relação gama-glutamil transferase e creatinina urinária (uGGT/uCr) (1,06 a 2,62U/mg) variara, apresentando aumento em todos os momentos. Já a elevação do gama-glutamil transferase (uGGT) (56,61 a 128,12 U/L) e da razão proteína e creatinina urinárias (RPC) (0,26 a 1,24) foram evidenciadas nos dois primeiros tempos. Uma redução na média do RPC, uGGT e uGGT/uCr foi observada 10-15 dias após a implantação do tratamento (OH). Apesar da elevação desses marcadores, a concentração de creatinina (1,11 a 1,40mg/dL), ureia (40,07 a 67,16mg/dL) e densidade urinária (1,027 a 1,028) sofreram poucas variações. Em piometra canina, as complicações renais agudas secundárias podem estar presentes, ainda que leve e transitória nos animais tratados. Os marcadores tubulares foram considerados precoces na injúria renal aguda. Além disso, a SDMA e o RPC antecederam as alterações de creatinina em todos os tempos analisados.(AU)

High Levels of Serum Bile Acids in COVID-19 Patients on Hospital Admission.

INTRODUCTION: Bile acids are signaling molecules with immune, metabolic and intestinal microbiota control actions. In high serum concentrations they increase inflammatory response from the liver-gut axis, until causing multiorgan failure and death; therefore, they may be associated with COVID-19's clinical progression, as a consequence of tissue and metabolic damage caused by SARS-CoV-2. While this topic is of considerable clinical interest, to our knowledge, it has not been studied in Cuba. OBJECTIVE: Study and preliminarily characterize patients admitted with a diagnosis of COVID-19 and high levels of serum bile acids. METHODS: A preliminary exploratory study was carried out with descriptive statistical techniques in 28 COVID-19 patients (17 women, 11 men; aged 19-92 years) who exhibited high levels of serum bile acids (≥10.1 µmol/L) on admission to the Dr. Luis Díaz Soto Central Military Hospital in Havana, Cuba, from September through November 2021. RESULTS: On admission patients presented hypocholesterolemia (13/28; 46.4%), hyperglycemia (12/28; 43.0%) and hyper gamma-glutamyl transpeptidase (23/28; 84.2%). Median blood glucose (5.8 mmol/L) and cholesterol (4.1 mmol/L) were within normal ranges (3.2‒6.2 mmol/L and 3.9‒5.2 mmol/L, respectively). Severe or critical stage was the most frequent (13/28) and median serum bile acids (31.6 µmol/L) and gamma-glutamyl transferase (108.6 U/L) averaged well above their respective normal ranges (serum bile acids: 0‒10 µmol/L; GGT: 9‒36 U/L). Arterial hypertension was the most frequent comorbidity (19/28; 67.9%). CONCLUSIONS: Severe or critical stage predominated, with serum bile acids and gamma-glutamyl transferase blood levels above normal ranges. The study suggests that serum bile acid is toxic at levels ≥10.1 µmol/L, and at such levels is involved in the inflammatory process and in progression to severe and critical clinical stages of the disease. In turn, this indicates the importance of monitoring bile acid homeostasis in hospitalized COVID-19 patients and including control of its toxicity in treatment protocols.

Vincristine sulfate treatment influence on kidney function of female dogs with transmissible venereal tumor / Influência do tratamento com sulfato de vincristina na função renal de cadela com tumor transmissível venéreo

Chemotherapy agents have some undesirable and non-selective cytostatic effects. Considering that kidneys are vulnerable to drug-induced toxicity, this study evaluated renal injury caused by vincristine sulfate (VS) in 12 female dogs diagnosed with transmissible venereal tumor (TVT). The animals were treated with VS (0.025 mg/kg IV) every 7 days for 4 weeks. During treatment, the animals were subjected to clinical examination, blood count, serum measurement of symmetric dimethylarginine (SDMA), blood urea nitrogen (BUN), creatinine, alanine aminotransferase, and alkaline phosphatase. In addition, urinalysis and urinary gamma-glutamyl transferase (GGT) measurements were performed. All parameters were determined three times: before beginning the treatment (T0), after 14 days (T1), and after 28 days (T2). During the study period, there were no changes in serum urea or creatinine levels, urine specific gravity, or persistent proteinuria. Furthermore, urinary GGT measurement did not indicate tubular lesions, and consistent elevation of SDMA was found in only one patient above the reference range. The results showed that weekly therapy with VS as a single agent for 28 days does not induce renal injury in most cases.(AU)

Os agentes quimioterápicos possuem efeitos citostáticos indesejáveis e não seletivos. Considerando a vulnerabilidade renal à toxicidade induzida por drogas, este estudo avaliou a lesão renal causada pelo sulfato de vincristina (VS) em 12 cadelas com diagnóstico de tumor venéreo transmissível (TVT). Os animais foram tratados com VS (0,025 mg / kg IV) a cada sete dias, durante quatro semanas. No transcurso do tratamento, os animais foram submetidos a exame clínico, hemograma, dosagem sérica de dimetilarginina simétrica (SDMA), nitrogênio ureico sanguíneo (BUN), creatinina, alanina aminotransferase e fosfatase alcalina. Além disso, foram realizadas análises de urina e medições de gama-glutamil transferase (GGT) urinária. Todos os parâmetros foram mensurados em três tempos, antes do início do tratamento (T0), aos 14 dias (T1) e aos 28 dias (T2). Durante o período do estudo, não houve alterações nas concentrações de ureia ou creatinina séricas, na gravidade específica da urina ou proteinúria persistente. Além disso, a medição de GGT urinária não indicou lesões tubulares, e elevação consistente de SDMA foi encontrada em apenas um paciente acima do intervalo de referência. Os resultados mostraram que a terapia semanal com VS como agente único por 28 dias não induz lesão renal na maioria dos casos.(AU)

Prevalence and predictors of elevated liver enzyme levels in Mexico: The Mexican National Health and Nutrition Survey, 2016.

INTRODUCTION AND OBJECTIVE: To determine the prevalence of elevated liver enzyme levels and the fatty liver index according to specific sociodemographic, clinical, anthropometric, and metabolic risk factors in Mexican adult population. MATERIAL AND METHODS: The present analysis was conducted using data from the Mexican National Health and Nutrition Survey 2016. For the present study, 3,490 adults with complete information on liver enzymes, sociodemographic, lifestyle, and metabolic factors were analyzed. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) levels were determined from blood samples. We computed the fatty liver Index (FLI), as a surrogate marker of non-alcoholic fatty liver disease. The associations are reported as adjusted odds ratios (OR) and 95% confidence intervals (95%CI). RESULTS: At the national level, the prevalence of high serum levels of ALT, AST, and GGT were 7.9%, 13.5, and 12.9 respectively. We observed that men had higher prevalences of altered ALT, GGT and FLI compared to women. Additionally, we observe that individuals with obesity, metabolic syndrome and insulin resistance are significantly more likely to present elevated concentrations of AST, ALT, GGT and FLI. Finally, we found that the subjects of the lowest socioeconomic level and indigenous population were more likely to present elevated levels of AST, ALT, GGT, and FLI. CONCLUSION: In Mexico, non-alcoholic fatty liver disease affect people with obesity, diabetes, and metabolic syndrome as well as men, subjects of low socioeconomic status, subjects who live in rural areas and indigenous population. Interventions to reduce this condition should be a public health priority.

Genotoxic risk in humans and acute toxicity in rats of a novel oral high-dose coenzyme Q10 oleogel.

Coenzyme Q10 (CoQ10) supplementation has demonstrated to be safe and effective in primary and secondary CoQ10 deficiencies. Previously, we have designed a high-dose CoQ10 oleogel (1 g/disk) with excipients used in quantities that do not represent any toxic risk. However, it was necessary to demonstrate their safety in the final formulation. Following this purpose, an acute toxicity study of the oleogel in rats was performed. Furthermore, the genotoxic risk was evaluated in human volunteers after CoQ10 supplementation with oleogel and compared to the solid form (1 g/three 00-size-capsules). In addition, the general health status and possible biochemical changes of the participants were determined using serum parameters. Results suggested the absence of adverse effects caused by the interaction of the components in the oleogel formulation. Therefore, we conclude that the designed novel high-dose CoQ10 oleogel was safe for oral consumption.

Hematological and Serum Biochemical Changes and Their Prognostic Value in Horses Spontaneously Poisoned by Crotalaria spectabilis.

Determining the prognosis of poisoning by plants containing pyrrolizidine alkaloids is usually challenging. This study aimed to identify important prognostic parameters that can determine the severity of spontaneous poisoning by Crotalaria spectabilis in horses. Blood samples from 42 horses spontaneously poisoned by oats contaminated with C. spectabilis seeds were evaluated. Complete blood counts (CBC) and serum biochemical tests [urea, creatinine, total protein, albumin, total and direct bilirubin concentrations, aspartate aminotransferase (AST), γ-glutamyl transferase (GGT), and creatine kinase (CK) activities] were performed. Horses were followed up for 12 months to determine the long-term survival rate; after 12 months, they were divided into two groups: survivors (n = 30) and non-survivors (n = 12). Horses spontaneously poisoned with C. spectabilis had higher levels of urea, globulin, bilirubin (total, direct, and indirect), AST, GGT, and CK than the reference values. Non-survivor horses showed significantly higher (p < 0.05) values of hemoglobin, GGT, and direct bilirubin than the survivor horses. Horses with serum GGT activity higher than 95 U/l had 14.0 times the risk of death compared to animals showing activities equal to or lower than this value, whereas horses with serum direct bilirubin concentration higher than 0.6 mg/dl (10.26 µmol/L) had 5.78 times the risk of death compared to the others. In summary, serum GGT activity and direct bilirubin concentration may be useful prognostic indicators for assessing the severity of C. spectabilis-poisoned horses.

Safety and bioactive potential of nanoparticles containing Cantaloupe melon (Cucumis melo L.) carotenoids in an experimental model of chronic inflammation.

The safety and bioactive potential of crude carotenoid extract from Cantaloupe melon nanoencapsulated in porcine gelatin (EPG) were evaluated in a chronic inflammatory experimental model. Animals were fed a high glycemic index and high glycemic load (HGLI) diet for 17 weeks and treated for ten days with 1) HGLI diet, 2) standard diet, 3) HGLI diet + crude carotenoid extract (CE) (12.5 mg/kg), and 4) HGLI diet + EPG (50 mg/kg). General toxicity signals were investigated, considering body weight, food intake, hematological, biochemical parameters, relative weight, morphology, and histopathology of organs. The biochemical parameters indicated the low toxicity of EPG. Acute hepatitis was observed in animals' livers, but CE and EPG groups presented improved tissue appearance. Chronic enteritis was observed in animals, with villi and intestinal glands preservation in the EPG group. The results suggest the safety and the bioactive effect of EPG, possibly related to its anti-inflammatory potential.

Panel-Based Next-Generation Sequencing for the Diagnosis of Cholestatic Genetic Liver Diseases: Clinical Utility and Challenges.

OBJECTIVE: To test the application of a target enrichment next-generation sequencing (NGS) jaundice panel in genetic diagnosis of pediatric liver diseases. STUDY DESIGN: We developed a capture-based target enrichment NGS jaundice panel containing 42 known disease-causing genes associated with jaundice or cholestasis and 10 pathway-related genes. During 2015-2017, 102 pediatric patients with various forms of cholestasis or idiopathic liver diseases were tested, including patients with initial diagnosis of cholestasis in infancy, progressive familial intrahepatic cholestasis, syndromic cholestasis, Wilson disease, and others. RESULTS: Of the 102 patients, 137 mutations/variants in 44 different genes were identified in 84 patients. The genetic disease diagnosis rate was 33 of 102 (32.4%). A total of 79 of 102 (77.5%) of patients had at least 1 heterozygous genetic variation. Those with progressive intrahepatic cholestasis or syndromic cholestasis in infancy had a diagnostic rate of 62.5%. Disease-causing mutations, including ATP8B1, ABCB11, ABCB4, ABCC2, TJP2, NR1H4 (FXR), JAG1, AKR1D1, CYP7B1, PKHD1, ATP7B, and SLC25A13, were identified. Nine patients had unpredicted genetic diagnosis with atypical phenotype or novel mutations in the investigational genes. We propose an NGS diagnosis classification categorizing patients into high (n = 24), moderate (n = 9), or weak (n = 25) levels of genotype-phenotype correlations to facilitate patient management. CONCLUSIONS: This panel enabled high-throughput detection of genetic variants and disease diagnosis in patients with a long list of candidate causative genes. A NGS report with diagnosis classification may aid clinicians in data interpretation and patient management.

Recovery of the Cholangiocytes After Ischemia and Reperfusion Injury: Ultra-Structural, Hystological and Molecular Assessment in Rats.

INTRODUCTION: Ischemia-reperfusion (I/R) injury of the liver is a common area of interest to transplant and hepatic surgery. Nevertheless, most of the current knowledge of I/R of the liver derives from the hepatocyte and little is known of what happens to the cholangiocytes. Herein, we assess the sequence of early events involved in the I/R injury of the cholangiocytes. METHODS: Sixty Wistar rats were randomized in a SHAM group and I/R group. Serum biochemistry, histopathology, immunohistochemistry, transmission electron microscopy (TEM) and laser capture microdissection (LCM) were used for group comparison. RESULTS: There was peak of alkaline phosphatase 24 h after IR injury, and an increase of aspartate aminotransferase and alanine aminotransferase after 6 h of reperfusion, followed by a return to normal levels 24 h after injury. The I/R group presented the liver parenchyma with hepatocellular degeneration up to 6 h, followed by hepatocellular necrosis at 24 h. TEM showed cholangiocyte injury, including a progressive nuclear degeneration and cell membrane rupture, beginning at 6 h and peaking at 24 h after reperfusion. Cytokeratin-18 and caspase-3-positive areas were observed in the I/R group, peaking at 24-h reperfusion. Anti-apoptotic genes Bcl-2 and Bcl-xl activity were expressed from 6 through 24 h after reperfusion. BAX expression showed an increase for 24 h. CONCLUSIONS: I/R injury to the cholangiocyte occurs from 6 through 24 h after reperfusion and a combination of TEM, immunohistochemistry and LCM allows a better isolation of the cholangiocyte and a proper investigation of the events related to the I/R injury. Apoptosis is certainly involved in the I/R process, particularly mediated by BAX.

High prevalence of a variety of autoantibodies in a population of hepatitis C virus-infected individuals.

Hepatitis C virus (HCV) infection has been related to self-reactivity, extrahepatic manifestations and autoimmune diseases. The main goals of this work were to study the prevalence of autoantibodies and their relationship with viral titers and biochemical markers of hepatic damage in patients infected with HCV. Autoantibodies (ANA, AMA, SMA, APC, LKM, DNAds, ANCA, ATG and RF) were determined in 73 individuals with chronic HCV infection and 44 healthy volunteers. The presence of these antibodies was related to demographic variables, viral titers and biochemical parameters. A high prevalence of autoantibodies, particularly for RF, that was associated with female gender was observed in HCV-infected patients. In addition, SMA, ANA and ATG showed increased frequencies in HCV infection. Interestingly, the concurrent detection of SMA and more than one autoantibody was associated with high gGT levels. Notably, concurrent higher gGT, HCV and SMA levels were observed in male patients as compared to their female counterparts. These results indicate a relationship between HCV infection and the concurrent detection of various autoantibodies in the absence of symptoms of autoimmune diseases. They also suggest a link among the presence of a variety of autoantibodies simultaneously with SMA, increased gGT levels and HCV titers in a population of male patients.

Ductular reaction, cytokeratin 7 positivity, and gamma-glutamyl transferase in multistage hepatocarcinogenesis in rats.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is characterized by multistage formation. The presence of ductular reaction, cytokeratin 7 positivity (PCK7), and increased levels of gamma glutamyltransferase (γGT) has been observed during liver carcinogenesis and contribute to tumor progression. Our goal was to evaluate the ductular reaction in multistage carcinogenesis and to correlate PCK7 and γGT levels with tumor incidence, histological characteristics, liver DNA damage index, and the expression of oxidative stress proteins. HCC was induced in 24 male Wistar rats weighing 145-150 g by chronic and intermittent exposure to 50 or 100 mg/kg diethylnitrosamine (DEN). Six control animals received only vehicle. Blood was collected to determine hepatic enzyme levels. Animals were divided into three groups: control (CO), precancerous lesions (PL), and advanced HCC. Liver samples were obtained for immunohistochemical analyses and the measurement of protein expression. Statistical analyses included Tukey's test and Pearson's correlation analyses. We observed an extensive ductular reaction in advanced HCC and a strong correlation between PCK7 and levels of γGT and the poor prognosis and aggressiveness of HCC. The extent of PCK7 and high γGT levels were associated with overexpression of inducible nitric oxide synthase (iNOS) and heat shock factor protein 1 (HSF-1). However, PCK7 and γGT levels were negatively correlated with protein expression of nuclear factor erythroid 2-related factor 2 (NRF2) and inducible heat shock protein 70 (iHSP70). These findings suggest that ductular reaction is involved in the progression of multistage hepatocarcinogenesis.

Avaliação dos níveis séricos das enzimas hepáticas e proteína C reativa em indivíduos com sobrepeso com e sem Síndrome Metabólica / Evaluation of serum levels of liver enzymes and C-reactive protein (CRP) in overweight individuals with and without metabolic syndrome

A Síndrome Metabólica (SM) é uma doença que envolve diversas alterações metabólicas, dentre elas, dislipidemia, intolerância à glicose, obesidade e hipertensão arterial. A alteração nos níveis das enzimas hepáticas tem se mostrado um marcador útil no diagnostico da SM. Há poucos trabalhos avaliando essas enzimas em indivíduos com sobrepeso com e sem SM. O presente trabalho avaliou os níveis séricos das enzimas hepáticas (ALT, AST,GGT) bem como a proteína C reativa (PCR) como marcador inflamatório em indivíduos com sobrepeso, come sem SM. Foram avaliados 97 indivíduos, sendo 41 controles saudáveis eutróficos (EU), 28 indivíduos com sobrepeso sem SM (OSSM) e 28 indivíduos com sobrepeso com SM (OCSM). As análises de colesterol total,HDL-C. LDL-C, triacilglicerol, glicose, ALT, AST e GGT foram efetuadas em um auto-analisador bioquímico.A determinação de PCR foi realizada por enzima imunoensaio em micropartículas (MEIA). Utilizou-se o teste não paramétrico de Kruskal-Wallis e os resultados foram apresentados sob a forma de mediana (mínimo máximo).Correlação de Spearman foi utilizada neste estudo. Os níveis séricos das enzimas hepáticas (ALT, AST e GGT) não diferiram entre o grupo EU e o grupo OSSM, entretanto, houve diferença estatisticamente significativa quando esses parâmetros foram comparados entre EU e OCSM e OSSM e OCSM (p<0,001). Níveis plasmáticos de glicose foram positivamente correlacionados com ALT, AST e GGT. O grupo OCSM apresentou aumento significativo nos níveis séricos de PCR quando comparado aos demais grupos (p<0,001).Conclui-se que o sobrepeso não foi capaz de alterar os níveis das enzimas hepáticas e da PCR e que a elevação dos níveis séricos de GGT pode ser considerada um fator de risco adicional para SM.

Metabolic syndrome (MetS) is a disease that involves several metabolic changes, including dyslipidemia, glucose intolerance, obesity and hypertension. The changes in liver enzyme levels have been shown to be a useful marker in the diagnosis of MetS. There are few studies evaluating these enzymes in overweight individuals with or without MetS. This study evaluated the serum levels of liver enzymes (ALT, AST, and GGT) as well as C-reactive protein (CRP) as inflammatory markers in overweight individuals with and without MS. We studied 97 subjects, 41 eutrophic healthy controls (EU), 28 overweight individuals without MetS (OSSM) and 28 overweight individuals with MetS (OCSM). Analyses of total cholesterol, HDL-C, LDL-C, triacylglycerol, fasting glucose, ALT, AST and GGT were performed in a biochemical auto analyzer. The determination was performed by CRP enzyme in microparticles (MEIA). The nonparametric Kruskal-Wallis test was performed and the results were presented as median (minimum-maximum). Spearman correlation was also performed in this study. Serum levels of liver enzymes (ALT, AST and GGT) did not differ between group EU and group OSSM, however, statistically significant differences when these parameters were compared between EU and OCSM and OSSM and OCSM (p <0.001). Glucose levels were positively correlated with ALT, AST and GGT.The group showed a significant increase in serum CRP when compared to other groups (p <0.001). We conclude that overweight was not able to alter the levels of liver enzymes and CRP levels and the elevation of serum GGT may be considered an additional risk factor for MetS.

Oxidative stress in the pathophysiology of metabolic syndrome: which mechanisms are involved? / Estresse oxidativo na fisiopatologia da síndrome metabólica: quais mecanismos estão envolvidos?

ABSTRACTMetabolic syndrome (MS) is a combination of cardiometabolic risk factors, including obesity, hyperglycemia, hypertriglyceridemia, dyslipidemia and hypertension. Several studies report that oxidative condition caused by overproduction of reactive oxygen species (ROS) plays an important role in the development of MS. Our body has natural antioxidant system to reduce oxidative stress, which consists of numerous endogenous and exogenous components and antioxidants enzymes that are able to inactivate ROS. The main antioxidant defense enzymes that contribute to reduce oxidative stress are superoxide dismutase (SOD), catalase (CAT) and gluthatione peroxidase (GPx). The high-density lipoprotein cholesterol (HDL-c) is also associated with oxidative stress because it presents antioxidant and anti-inflammatory properties. HDL-c antioxidant activity may be attributed at least in part, to serum paraoxonase 1 (PON1) activity. Furthermore, derivatives of reactive oxygen metabolites (d-ROMs) also stand out as acting in cardiovascular disease and diabetes, by the imbalance in ROS production, and close relationship with inflammation. Recent reports have indicated the gamma-glutamyl transferase (GGT) as a promising biomarker for diagnosis of MS, because it is related to oxidative stress, since it plays an important role in the metabolism of extracellular glutathione. Based on this, several studies have searched for better markers for oxidative stress involved in development of MS.

RESUMOA síndrome metabólica (SM) representa uma conjunção de fatores de risco cardiometabólicos, incluindo obesidade, hiperglicemia, hipertrigliceridemia, dislipidemia e hipertensão. Vários estudos reportam que a condição oxidativa causada pela superprodução de espécies reativas de oxigênio (EROs) desempenha importante papel no desenvolvimento da SM. Nosso organismo apresenta sistema antioxidante natural para diminuir o estresse oxidativo, o qual consiste em numerosos componentes endógenos e exógenos e enzimas antioxidantes que são capazes de inativar as EROs. As principais enzimas de defesa antioxidante que contribuem para o processo de redução do estresse oxidativo são a superóxido dismutase (SOD), a catalase (CAT) e a glutationa peroxidase (GPx). O colesterol associado à lipoproteína de alta densidade (HDL-c) também está relacionado com o estresse oxidativo por apresentar propriedades antioxidantes e anti-inflamatórias. A atividade antioxidante do HDL-c pode ser atribuída, pelo menos em parte, à atividade da paraoxonase 1 (PON1) sérica. Além disso, os metabólitos derivados de oxigênio reativo (d-ROMs) também se destacam como atuantes nas doenças cardiovasculares e no diabetes, pelo desequilíbrio na produção de EROs, tendo relação importante com a inflamação. Relatos recentes vêm apontando a gama-glutamiltransferase (GGT) como biomarcador promissor para diagnóstico da SM, pois esta se associa ao estresse oxidativo, uma vez que desempenha papel relevante no metabolismo extracelular de glutationa. Com base nisso, vários estudos vêm buscando melhores marcadores do estresse oxidativo e sua relação com o desenvolvimento da SM.

Oxidative stress and cell damage in a model of precancerous lesions and advanced hepatocellular carcinoma in rats.

Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer deaths throughout the world. This study was aimed to analyze oxidative stress and cell damage in a multistage model of liver carcinogenesis induced by diethylnitrosamine (DEN) in rats. Male Wistar rats weighing 145-150 g were divided into three groups: control, precancerous lesions (PL) (which received 100 mg DEN once a week every 6 weeks up to 28 weeks), and advanced HCC (50 mg DEN once/twice per week up to 19 weeks). Lipid peroxidation (TBARS), superoxide dismutase (SOD) activity, and expression of transforming growth factor-1 beta (TGF)-1ß, endothelial and inducible nitric oxide syntahese (eNOS, iNOS), NADPH quinone oxireductase (NQO)-1, nuclear factor erythroid 2-related factor (NrF)2, kelch-like ECH-associated protein (Keap)1 and heat shock protein (HSP)70 were measured. TBARS concentration was augmented in the PL and advanced HCC groups. SOD activity, TGF-1ß and Nrf2 expression were higher in animals with precancerous lesions. In advanced HCC, expression of NQO1 and iNOS increased while there was a decrease in HPS70 expression. Data obtained provide evidence for the differential activation of proteins involved in oxidative stress and cell damage during progression of carcinogenesis in an animal model of HCC.

Liver enzymes serum levels in patients with chronic kidney disease on hemodialysis: a comprehensive review

We reviewed the literature regarding the serum levels of the enzymes aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase in patients with chronic kidney disease on hemodialysis with and without viral hepatitis. Original articles published up to January 2013 on adult patients with chronic kidney disease on hemodialysis were selected. These articles contained the words “transaminases” “aspartate aminotransferase” “alanine aminotransferase” “gamma glutamyl transferase,” “liver enzymes”, AND “dialysis” OR “hemodialysis”. A total of 823 articles were retrieved. After applying the inclusion and exclusion criteria, 49 articles were selected. The patients with chronic kidney disease on hemodialysis had reduced serum levels of aminotransferases due to hemodilution, lower pyridoxine levels, or elevated homocysteine levels. The chronic kidney disease patients on hemodialysis infected with the hepatitis C virus also had lower aminotransferase levels compared with the infected patients without chronic kidney disease. This reduction is in part due to decreased viremia caused by the dialysis method, the production of a hepatocyte growth factor and endogenous interferon-α, and lymphocyte activation, which decreases viral action on hepatocytes. Few studies were retrieved on gamma-glutamyl transferase serum levels; those found reported that there were no differences between the patients with or without chronic kidney disease. The serum aminotransferase levels were lower in the patients with chronic kidney disease on hemodialysis (with or without viral hepatitis) than in the patients with normal renal function; this reduction has a multifactorial origin.

Serum copper and copper related liver enzymes in sheep from Rio Grande do Sul, Brazil / Cobre sérico e enzimas relacionadas ao seu metabolismo em ovinos do Rio Grande do Sul

The aim of this work was to determine serum copper levels, aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT) activity in purebred show sheep fed concentrate and field sheep raised on natural pastures of Rio Grande do Sul, the southernmost State of Brazil. Blood samples of 120 show sheep and 110 field raised animals were collected independently of age, sex and breed. Mean serum levels of copper found on purebred and field sheep were 66.14 ± 9.76 and 62.01 ± 16.36 µg/dl (P<0.0357), respectively. AST activity was higher in show sheep than in field animals (85.01 ± 40.02 vs. 65.58 ± 16.19 IU, P<0.0001). GGT activity levels found were 41.02 ± 10.61 and 41.91 ± 9.49 IU, with no significant differences between groups. It is concluded that serum copper levels of purebred show sheep group were within international reference values for the species, whereas in the grass grazed group, the level of this mineral was bellow the lower limit in several individuals. Enhanced AST serum activity in blood samples of show sheep examined appear to be related to copper liver levels detected in these animals.

O objetivo desse trabalho foi identificar as concentrações séricas de cobre enzimas aspartatoaminotransferase (AST) e gamaglutamiltransferase (GGT), tanto em ovinos preparados para exposição e alimentados com concentrados como criados a campo, a fim de contribuir para a formação de valores de referência e auxiliar no prognóstico da saúde desses animais. Colheram-se 120 amostras de sangue de animais de exposição e 110 de animais de campo, independente de sexo, raça e idade. Os níveis séricos médios de cobre, AST e GGT dos animais de exposição e a campo foram iguais a 66,14 ± 9,76 e 62,01 ± 16,36 µg/kg (P<0,0357); 85,01 ± 40,02 e 65,58 ± 16,19 UI (P<0,0001); 41,02 10,61 e 41,91 ± 9,49 UI (P>0.05), respectivamente. Em conclusão, a concentração de cobre em ovinos preparados para exposição mostraram-se dentro dos valores de referência e as de alguns animais mantidos a campo abaixo do intervalo fisiológico. Os níveis séricos de AST aumentados no grupo exposição parecem estar relacionados com o acúmulo hepático de cobre.

Avaliação da transferência de imunidade passiva em cordeiros com até 30 dias de idade / Passive transfer immunity valuation in lambs with until 30 days of life

O objetivo deste estudo foi determinar as concentrações séricas de imunoglobulina G, PT e de sua fração eletroforética gama globulina, assim como a atividade enzimática de GGT e ALP. Estabeleceu-se a possibilidade da atividade destas enzimas ser utilizada indiretamente como indicadoras de um adequado nível de proteção humoral e/ou como falha de transferência de imunidade passiva em cordeiros. Foi pesquisada a correlação entre as variáveis em quatro grupos de idade divididos em até 30 dias de vida. Para tanto, foram coletadas 191 amostras de sangue de cordeiros em 21 propriedades da região de Araçatuba - São Paulo. Realizaram-se os testes de imunodifusão radial, espectrofotometria e eletroforese para obtenção dos valores de IgG, PT e γ globulina, respectivamente. Para os valores da atividade de GGT e ALP, foram utilizados kits comerciais. Notou-se correlação significativa entre ALP e GGT, fato observado também com PT, IgG e GGT. A gama-globulina mostrou-se correlacionada com GGT, IgG e PT. A atividade de FA não deve ser utilizada como indicadora de transferência de imunidade passiva em cordeiros.

The aim of this study was to determine the serum concentrations of immunoglobulin G, TP and the gamma globulin electrophoretic fraction, as well as the enzymatic activities of GGT and ALP. This was done in order to explore the possibility of using changes in activities of these enzymes as indirect indicators of adequate humoral immunity and/ or failure of immune passive transfer in lambs. Pearson correlation was performed between variable of four groups of age during the first 30 days of life. Blood samples (191) from lambs from 21 different farms in Araçatuba region- São Paulo. The following tests were perfomed: radial immunodiffusion, spectrophotometry and electrophoresis to stain the amount of IgG, TP and gamma globulin, respectively. GGT and ALP values were determinate using commercial kits. There was a statistically significant correlation between ALP and GGT. The same correlation was observed from TP, IgG and GGT. A positive gamma globulin correlation was found between GGT, IgG and TP. ALP activity cannot be used as an indicator of immune passive transfer.

Avaliação da transferência de imunidade passiva em cordeiros com até 30 dias de idade / Passive transfer immunity valuation in lambs with until 30 days of life

O objetivo deste estudo foi determinar as concentrações séricas de imunoglobulina G, PT e de sua fração eletroforética gama globulina, assim como a atividade enzimática de GGT e ALP. Estabeleceu-se a possibilidade da atividade destas enzimas ser utilizada indiretamente como indicadoras de um adequado nível de proteção humoral e/ou como falha de transferência de imunidade passiva em cordeiros. Foi pesquisada a correlação entre as variáveis em quatro grupos de idade divididos em até 30 dias de vida. Para tanto, foram coletadas 191 amostras de sangue de cordeiros em 21 propriedades da região de Araçatuba - São Paulo. Realizaram-se os testes de imunodifusão radial, espectrofotometria e eletroforese para obtenção dos valores de IgG, PT e γ globulina, respectivamente. Para os valores da atividade de GGT e ALP, foram utilizados kits comerciais. Notou-se correlação significativa entre ALP e GGT, fato observado também com PT, IgG e GGT. A gama-globulina mostrou-se correlacionada com GGT, IgG e PT. A atividade de FA não deve ser utilizada como indicadora de transferência de imunidade passiva em cordeiros.(AU)

The aim of this study was to determine the serum concentrations of immunoglobulin G, TP and the gamma globulin electrophoretic fraction, as well as the enzymatic activities of GGT and ALP. This was done in order to explore the possibility of using changes in activities of these enzymes as indirect indicators of adequate humoral immunity and/ or failure of immune passive transfer in lambs. Pearson correlation was performed between variable of four groups of age during the first 30 days of life. Blood samples (191) from lambs from 21 different farms in Araçatuba region- São Paulo. The following tests were perfomed: radial immunodiffusion, spectrophotometry and electrophoresis to stain the amount of IgG, TP and gamma globulin, respectively. GGT and ALP values were determinate using commercial kits. There was a statistically significant correlation between ALP and GGT. The same correlation was observed from TP, IgG and GGT. A positive gamma globulin correlation was found between GGT, IgG and TP. ALP activity cannot be used as an indicator of immune passive transfer.(AU)