Prospective Protective Effects of Arthrospira platensis Against Acetaminophen Induced Hepato-Renal Toxicity in Rats / Efectos Protectores Prospectivos de Arthrospira platnesis Contra la Toxicidad Hepatorrenal Inducida por Paracetamol en Ratas

SUMMARY: The toxic effects of acetaminophen appear primarily in the liver and kidney. The protective effect of blue green alga Arthrospira platensis on hepato-renal toxicity caused by acetaminophen was evaluated in male rats. The obtained results showed that subcutaneous injection of acetaminophen at a dose 120 &240 սl acetaminophen/kg by weight resulted in an observed elevation in the enzyme activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and Alkaline phosphatase (ALP), serum total lipids, total cholesterol, creatinine, total bilirubin, urea, nitric oxide (NO), L- malondialdehyde (MDA) and interleukins (IL-2 &IL-6). However, there is a decrease in the serum total protein, albumin and loss in antioxidant enzyme activities in liver including; superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GSH). This effect was found to be dose and time dependent. In spite of, pre- oral administration of Arthrospira platensis 1000 mg/kg .b. wt. prior acetaminophen injection succeeded to modulate the effect of the observed abnormalities caused by acetaminophen. Moreover, there were no remarkable changes in serum biomarkers of rats received Arthrospira platensis only at a dose of 1000 mg/kg by weight (group 2). The histopathological findings confirm the biochemical results that indicates the safety use of Arthrospira platensis at the selected dose in this study. Therefore, the present results clarified the protective effect of blue green alga Arthrospira platensis on oxidative stress, hepatic and nephrotoxicity induced by acetaminophen in male Wister rats.

Los efectos tóxicos del paracetamol aparecen principalmente en el hígado y el riñón. Se evaluó en ratas macho Wistar el efecto protector del alga verde azulada Arthrospira platensis sobre la toxicidad hepatorrenal causada por paracetamol. Los resultados obtenidos mostraron que la inyección subcutánea de paracetamol a dosis de 120 y 240 µl de paracetamol/kg, resultó en una elevación en las actividades enzimáticas de la aspartato aminotransferasa (AST), alanina aminotransferasa (ALT) y fosfatasa alcalina (ALP), lípidos séricos totales, colesterol total, creatinina, bilirrubina total, urea, óxido nítrico (NO), L- malondialdehído (MDA) e interleucinas (IL-2 e IL-6). Sin embargo, hay una disminución en la proteína sérica total, albúmina y pérdida en las actividades de las enzimas antioxidantes en el hígado, incluyendo; superóxido dismutasa (SOD), catalasa (CAT) y glutatión reductasa (GSH). Se encontró que este efecto era dependiente de la dosis y el tiempo. A pesar de la administración preoral de Arthrospira platensis 1000 mg/kg, la inyección previa de acetaminofeno logró modular el efecto de las anormalidades observadas causadas por el acetaminofeno. Además, no hubo cambios notables en los biomarcadores séricos de ratas que recibieron Arthrospira platensis solo a una dosis de 1000 mg/kg (Grupo 2). Los hallazgos histopatológicos confirman los resultados bioquímicos que indican la seguridad del uso de Arthrospira platensis a la dosis seleccionada en este estudio. Por lo tanto, los presentes resultados aclararon el efecto protector del alga verde azulada Arthrospira platensis sobre el estrés oxidativo, la toxicidad hepática y la nefrotoxicidad inducida por paracetamol en ratas Wistar macho.

Precise application of Beichaihu and Nanchaihu in classical formulas / 中国中药杂志

To maintain the precision and stability of the efficacy of classical formulas, this study compared the origins and specifications of Bupleuri Radix and revealed the precise application regularity of Bupleurum chinense(Beichaihu) and Bupleurum scorzonerifolium(Nanchaihu) in classical formulas. The efficacy and indications of formulas with Bupleuri Radix as the sovereign drug in the Treatise on Cold Damage and Miscellaneous Diseases(Shang Han Za Bing Lun) were investigated. The difference in the efficacy of Bupleuri Radix as well as the differences in the chemical composition, and liver-protecting and lipid-lowering effects of the decoctions of Beichaihu and Nanchaihu were analyzed with LC-MS technology based on the CCl_4-induced liver injury model in mice and sodium oleate-induced HepG2 hyperlipidemia cell model. The results showed that seven classical formulas with Bupleuri Radix as the sovereign drug in the Treatise on Cold Damage and Miscellaneous Diseases were mainly used in the treatment of digestive, metabolic, immune, circulatory, and other diseases. Bupleuri Radix mainly played the functions of protecting the liver, benefiting the gallbladder, and lowering the lipid, and had different focuses in different formulas. There were 14 differential components in the decoctions of Beichaihu and Nanchaihu, and the chemical structures of 11 components were identified, including 10 saponins and one flavonoid. The results of the liver-protecting efficacy experiment showed that compared with the Nanchaihu decoction, Beichaihu decoction could reduce the serum aspartate aminotransferase(AST) activity in liver injury model mice(P<0.01). The results of the lipid-lowering efficacy experiment proved that Beichaihu and Nanchaihu decoctions both showed highly significant differences in lowering the total cholesterol(TC) and triglyceride(TG) content in HepG2 cells(P<0.01), and Nanchaihu decoction was superior to Beichaihu decoction in lowering the lipid. The results of this study preliminarily proved that there were differences in chemical composition, and liver-protecting and lipid-lowering effects of Beichaihu and Nanchaihu decoctions, indicating that it was necessary to determine the precise origin of Bupleuri Radix in the clinical formulation of traditional Chinese medicine. The study provides a scientific basis for both precise clinical medication and purpose-based accurate quality evaluation of traditional Chinese medicine in clinical application.

Effects of Li-Dan-He-Ji on regulating oxidative stress and antagonising infantile cholestatic hepatic fibrosis / 中华危重病急救医学

OBJECTIVE@#To explore the clinical effect of Li-Dan-He-Ji in the treatment of infantile cholestatic hepatic fibrosis.@*METHODS@#Patients who met the diagnostic criteria of infantile cholestatic hepatic fibrosis in the department of integrated traditional Chinese and Western medicine and the department of gastroenterology of Wuhan Children's Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from January to December 2021 were included in the study by prospective randomized controlled trial. They were divided into the conventional treatment group and Li-Dan-He-Ji group according to the random number table. The patients in the conventional treatment group were given conventional treatment according to the guidelines. In the Li-Dan-He-Ji group, the self-made Chinese medicinal compound Li-Dan-He-Ji (prescription: Herba Artemisiae Scopariae, Fructus Forsythiae, Radix et Rhizoma Rhei preparata, Radix Polygoni Multiflori Preparata, Radix Paeoniae Rubra, Ramulus Cinnamomi, Fructus Aurantii, Rhizoma Atractylodis Macrocephalae, Fructus Schisandrae Chinensis, Carapax Trionycis, and Radix Glycyrrhizae) was given on the basis of the routine treatment, by oral, enema or nasal feeding, 60 mL each day, divided into 2 or 3 times, for 28 days. Outpatient follow-up was maintained for 4 weeks. Before and after treatment, serum liver fibrosis 4 items [type IV collagen (IV-C), hyaluronidase (HA), type III procollagen (PC III), laminin (LN)], liver function and cholestasis-related markers [total bilirubin (TBil), direct bilirubin (DBil), total bile acid (TBA), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST)], oxidative stress markers [superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH)], liver stiffness measurement (LSM) detected by transient elastography (TE), aspartate aminotransferase-to-platelet ratio index (APRI), and liver and spleen retraction time were recorded in the two groups.@*RESULTS@#During the observation period, a total of 40 cases of cholestatic hepatic fibrosis were treated, including 21 cases in the conventional treatment group and 19 cases in the Li-Dan-He-Ji group. Before treatment, the differences in serum liver fibrosis 4 items, serum liver function and cholestasis-related markers, oxidative stress indexes, LSM and APRI of the two groups were not statistically significant. After treatment, the liver fibrosis 4 items, liver function and cholestasis-related markers, LSM, and APRI were all significantly decreased in both groups, and the indexes in the Li-Dan-He-Ji group were significantly lower than those in the conventional treatment group [HA (ng/L): 165.81±21.57 vs. 203.87±25.88, PC III (μg/L): 69.86±9.32 vs. 81.82±7.39, IV-C (μg/L): 204.14±38.97 vs. 239.08±24.93, LN (μg/L): 162.40±17.39 vs. 190.86±15.97, TBil (μmol/L): 37.58±27.63 vs. 53.06±45.09, DBil (μmol/L): 20.55±19.34 vs. 30.08±27.39, ALP (U/L): 436.50±217.58 vs. 469.60±291.69, γ-GGT (U/L): 66.78±35.84 vs. 87.00±32.82, ALT (U/L): 64.75±50.53 vs. 75.20±50.19, AST (U/L): 77.25±54.23 vs. 96.80±59.77, TBA (μmol/L): 74.35±44.44 vs. 85.45±39.50, LSM (kPa): 5.24±0.39 vs. 7.53±3.16, APRI: 0.52±0.39 vs. 0.98±0.29, all P < 0.05]. After treatment, MDA in the two groups were significantly lower than those before treatment, and SOD and GSH were significantly higher than those before treatment. The level of SOD in the Li-Dan-He-Ji group was significantly higher than that in the conventional treatment group (kU/L: 64.56±6.69 vs. 51.58±5.98, P < 0.05). In addition, the liver retraction time (day: 20.13±10.97 vs. 24.33±13.46) and spleen retraction time (day: 25.93±13.01 vs. 29.14±14.52) in the Li-Dan-He-Ji group were significantly shorter than those in the conventional treatment group (both P < 0.05).@*CONCLUSIONS@#The use of Li-Dan-He-Ji in the treatment of cholestatic hepatic fibrosis can effectively improve the indicators of cholestasis, hepatic fibrosis, oxidative stress and clinical symptoms in children.

Application of a low copper diet guidance based on food exchange portions in children with hepatolenticular degeneration / 中国当代儿科杂志

OBJECTIVES@#To study the efficacy of a low-copper diet guidance based on food exchange portions in children with hepatolenticular degeneration.@*METHODS@#A self-controlled study was conducted from July 2021 to June 2022, including 30 children under the age of 18 who were diagnosed with hepatolenticular degeneration and poorly controlled with a low-copper diet. During the medical visit, personalized low-copper diet guidance was provided to the children and their parents using a copper-containing food exchange table and a copper food exchange chart. During home care, compliance with the low-copper diet of the children was improved by recording dietary diaries and conducting regular follow-ups. The changes in 24-hour urine copper level, liver function indicators, and the low-copper diet knowledge of the children's parents were observed before and after the intervention, with no change in the original drug treatment.@*RESULTS@#After 8, 16, and 24 weeks of intervention, the 24-hour urine copper level decreased significantly compared to before intervention (P<0.05). When compared to 8-week intervention, the urine copper level decreased significantly after 16 and 24 weeks of intervention. The 24-hour urine copper level after 24 weeks of intervention decreased significantly compared to 16 weeks of intervention (P<0.05).After 24 weeks of intervention, the alanine aminotransferase and aspartate aminotransferase levels decreased significantly compared to before intervention (P<0.05). Additionally, in 16 of the cases (53%), alanine aminotransferase and aspartate aminotransferase returned to normal levels. Following 8 weeks of intervention, the low-copper diet knowledge of the children's parents increased significantly (P<0.05).@*CONCLUSIONS@#A low-copper diet guidance based on food exchange portions can effectively decrease the urine copper level and improve liver function in children with hepatolenticular degeneration. Furthermore, it can increase the low-copper diet knowledge of the children's parents.

Les perturbations des enzymes ASAT, ALAT et LDH au cours du paludisme de l'adulte au Nord-est de la RDC / NA

Introduction : la présente étude avait pour objectif de ressortir certaines anomalies des enzymes hépatiques portant sur l'ASAT, l'ALAT et la LDH chez les patients impaludés en vue de contribuer à la prise en charge diagnostique du paludisme dans la ville de Butembo. Méthodes. Cette étude est descriptive. Elle a été réalisée dans le service de Médecine Interne et de Parasitologie de l'Hôpital Matanda du 1er juillet 2020 au 2 novembre 2020 soit pendant une période de 4 mois. Elle a porté sur une série de 100 patients impaludés avec goutte épaisse positive. Les paramètres d'intérêt étaient les caractéristiques sociodémographiques, les anomalies des enzymes hépatiques (ASAT, ALAT, LDH) et la densité parasitaire. Résultats : 100 patients ont été sélectionnés au cours de notre étude parmi lesquels 54 sujets de sexe féminin et 46 de sexe masculin. Le taux de LDH était élevé dans 73% des cas. Les transaminases ASAT et ALAT étaient élevées dans 28% et 31% des cas respectivement. Aucune corrélation significative n'a été retrouvée entre la densité parasitaire et les anomalies enzymatiques observées dans notre étude. Conclusion. Des variations notables des paramètres biologiques portant sur les anomalies de enzymes hépatiques dont l'ASAT, l'ALAT et la LDH ont été enregistrés au cours de l'accès palustre à Plasmodium falciparum chez l'adulte de la ville de Butembo. Ces paramètres pourraient avoir une utilité dans le diagnostic du paludisme et /ou constituer un indicateur de la sévérité de la maladie, spécialement lorsque les résultats parasitologiques ne sont pas disponibles ou sont incertains.

Deficiency in glutathione synthesis and reduction contributes to the pathogenesis of colitis-related liver injury / 中南大学学报(医学版)

OBJECTIVES@#Liver disease is the most common extra-intestinal manifestation of ulcerative colitis (UC), but the underlying pathogenesis is still not clarified. It is well accepted that the occurrence of UC-related liver disease has close correlation with immune activation, intestinal bacterial liver translocation, inflammatory cytokine storm, and the disturbance of bile acid circulation. The occurrence of UC-related liver disease makes the therapy difficult, therefor study on the pathogenesis of UC-related liver injury is of great significance for its prevention and treatment. Glutathione (GSH) shows multiple physiological activities, such as free radical scavenging, detoxification metabolism and immune defense. The synthesis and the oxidation-reduction all contribute to GSH antioxidant function. It is reported that the deficiency in hepatic GSH antioxidant function participates in multiple liver diseases, but whether it participates in the pathogenesis of UC-related liver injury is still not clear. This study aims to investigate the feature and underlying mechanism of GSH synthesis and oxidation-reduction function during the development of UC, which will provide useful information for the pathogenesis study on UC-related liver injury.@*METHODS@#UC model was induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS)-ethanol solution (5 mg/0.8 mL per rat, 50% ethanol) via intra-colonic administration in rats, and the samples of serum, liver, and colon tissue of rats were collected at the 3rd, 5th, and 7th days post TNBS. The severity degree of colitis was evaluated by measuring the disease activity index, colonic myeloperoxidase activity, and histopathological score, and the degree of liver injury was evaluated by histopathological score and the serum content of alanine aminotransferase. Spearman correlation analysis was also conducted between the degree of colonic lesions and index of hepatic histopathological score as well as serum aspartate aminotransferase level to clarify the correlation between liver injury and colitis. To evaluate the hepatic antioxidant function of GSH in UC rats, hepatic GSH content, enzyme activity of GSH peroxidase (GSH-Px), and GSH reductase (GR) were determined in rats at the 3rd, 5th, and 7th days post TNBS, and the protein expressions of glutamine cysteine ligase (GCL), GSH synthase, GSH-Px, and GR in the liver of UC rats were also examined by Western blotting.@*RESULTS@#Compared with the control, the disease activity index, colonic myeloperoxidase activity, and histopathological score were all significantly increased at the 3rd, 5th, and 7th days post TNBS (all P<0.01), the serum aspartate aminotransferase level and hepatic histopathologic score were also obviously elevated at the 7th day post TNBS (all P<0.05). There was a significant positive correlation between the degree of liver injury and the severity of colonic lesions (P=0.000 1). Moreover, compared with the control, hepatic GSH content and the activity of GSH-Px and GR were all significantly decreased at the 3rd and 5th days post TNBS (P<0.05 or P<0.01), and the protein expressions of GCL, GSH-Px, and GR were all obviously down-regulated at the 3rd, 5th, and 7th days post TNBS (P<0.05 or P<0.01).@*CONCLUSIONS@#There is a significant positive correlation between the degree of liver injury and the severity of colonic lesions, and the occurrence of reduced hepatic GSH synthesis and decreased GSH reduction function is obviously earlier than that of the liver injury in UC rats. The reduced hepatic expression of enzymes that responsible for GSH synthesis and reduction may contribute to the deficiency of GSH synthesis and oxidation-reduction function, indicating that the deficiency in GSH antioxidant function may participate in the pathogenesis of UC related liver injury.

Study of clinical characteristics in patients with gp210 antibody-positive primary biliary cholangitis / 中华肝脏病杂志

Objective: To analyze the clinical characteristics and prognostic value of liver function in a large samples of patients with anti-glycoprotein 210 (gp210 antibody) positive primary biliary cholangitis (PBC). Methods: A retrospective study was performed on 931 PBC cases in Beijing You'an Hospital affiliated to Capital Medical University from 2010 to 2019. According to the detection of gp210 antibody, 318 cases were divided into gp210 antibody positive group (positive group) and 613 cases were divided into gp210 antibody negative group (negative group). The differences in demographic, medical history, clinical indicators, B-ultrasound and pathological indicators as well as the histopathological basis were compared between the two groups. SPSS 16.0 software was used for statistical analysis. Measurement data were analyzed by t-test or rank sum test, and enumeration data by χ2 test. Multivariate analysis was used for logistic test, and and survival analysis was used for prognosis. Results: The positive and the negative groups were compared. The ratio of male to female was significantly higher in positive than negative group (1:5.35 vs. 1:9.73, P＜0.05), and the difference was statistically significant. The proportion of hormone use in history of past diagnosed and treated was higher in positive than negative group (12.9% vs. 3.47%, P＜0.05), and the difference was statistically significant. The detection of biochemical indexes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), alkaline phosphatase (ALP), glutamyl transpeptidase (GGT) were higher in positive than the negative group (51.1 U/L vs. 41.1 U/L, 62.6 U/L vs. 49.6 U/L, 24.1 μmol/L vs. 17.9 μmol/L, 228.3 U/L vs. 169.6 U/L, 203.9 U/L vs. 147.6 U/L), (P＜0.05), and the differences were statistically significant. Antinuclear antibody (ANA)-positive rate, high titer ratio and immunoglobulin G (IgG) levels were higher in positive than negative group (95.2% vs. 81.6%, 69.7% vs. 48.8%, 17.2 g/L vs. 16.2 g/L), (P＜0.05), and the differences were statistically significant. The incidence of liver failure was higher in positive than negative group (P＜0.05). CK7 and inflammation score were higher in positive group than negative group in liver histopathological observations (0.83±0.53 vs. 0.28±0.47; 1.06±0.39 vs. 0.54±0.65), (P＜0.05), and the differences were statistically significant. Conclusion: The illness condition of patients with gp210 antibody positive PBC is more severe than patients with gp210 antibody negative PBC, and the incidence of liver failure is significantly increased. Cholangiocytes may be the histopathological basis of the clinical characteristics of gp210 antibody positive PBC patients.

Study on the diagnostic value of transient elastography, APRI and FIB-4 for liver fibrosis in children with non-alcoholic fatty liver disease / 中华肝脏病杂志

Objective: To evaluate the diagnostic value of transient elastography, aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis index based on 4 factors (FIB-4) for liver fibrosis in children with non-alcoholic fatty liver disease (NAFLD). Methods: A retrospective study was conducted on 100 cases of nonalcoholic fatty liver disease in Hunan Children's Hospital between August 2015 to October 2020 to collect liver tissue pathological and clinical data. The receiver operating characteristic curve (ROC curve) was used to analyze the diagnostic value of liver stiffness measurement (LSM), APRI and FIB-4 in the diagnosis of different stages of liver fibrosis caused by NAFLD in children. Results: The area under the ROC curve (AUC) value of LSM, APRI and FIB-4 for diagnosing liver fibrosis (S≥1) were 0.701 [95% confidence interval (CI): 0.579 ~ 0.822, P = 0.011], 0.606 (95%CI: 0.436 ~ 0.775, P = 0.182), and 0.568 (95%CI: 0.397 ~ 0.740, P = 0.387), respectively. The best cut-off values were 6.65 kPa, 21.20, and 0.18, respectively. The AUCs value of LSM, APRI, and FIB-4 for diagnosing significant liver fibrosis (S≥ 2) were 0.660 (95% CI: 0.552 ~ 0.768, P = 0.006), 0.578 (95% CI: 0.464 ~ 0.691, P = 0.182) and 0.541 (95% CI: 0.427 ~ 0.655, P = 0.482), respectively. The best cut-off values were 7.35kpa, 24.78 and 0.22, respectively. The AUCs value of LSM, APRI and FIB-4 for the diagnosis of advanced liver fibrosis (S≥ 3) were 0.639 (95% CI: 0.446 ~ 0.832, P = 0.134), 0.613 (95% CI: 0.447 ~ 0.779, P = 0.223) and 0.587 (95% CI: 0.411 ~ 0.764, P = 0.346), respectively. The best cut-off values were 8.55kpa, 26.66 and 0.27, respectively. Conclusion: The transient elastography technique has a better diagnostic value than APRI and FIB-4 for liver fibrosis in children with NAFLD.

Quantitative Assessment of Dentine Sialophosphoprotein, Aspartate Aminotransferase and Lactate Dehydrogenase in Gingival Crevicular Fluid of Teeth with Root Resorption

ABSTRACT@#Root resorption is a shortening of root dentine which occurs physiologically in deciduous teeth. The present study aimed to quantify dentine sialophosphoprotein (DSPP), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) in gingival crevicular fluid (GCF) during the physiological process of root resorption of deciduous teeth. A cross-sectional study was conducted with 25 children aged between 4 and 10 years old. GCF was collected from the gingival sulcus using periopaper strips from the upper first deciduous molar (n = 45). The samples were divided equally into three groups, no resorption (R0), moderate resorption (RM) and severe resorption (RS), based on the existing radiographs taken. The GCF samples were then analysed using an enzyme-linked immunosorbent assay (ELISA) kit to determine the DSPP concentration levels and BioAssays System kit for AST and LDH. One-way ANOVA was used to determine the statistical differences between the means of the DSPP, AST and LDH concentration level in the three groups. A difference was considered significant when p < 0.05. High concentration levels of DSPP were significantly noted in RS (p < 0.05), compared to RM and R0. AST also portrayed significant high activity level (p < 0.05) similar to DSPP but LDH showed no significant changes between groups (p > 0.05). The high quantification of DSPP and AST levels in the severe and moderately resorbed roots indicated the potential use of this protein as a biomarker for detecting moderate-severe stages of root resorption.

Effect of kefir on increased apoptosis in liver and kidney in cisplatin toxicity / Efecto del kéfir sobre el aumento de la apoptosis en el hígado y los riñones en la toxicidad del cisplatino

SUMMARY: Cisplatin is a chemotherapeutic agent inducing liver and kidney damage. In this study, we intended to investigate the impact of kefir beverage, an essential probiotic and functional food, on liver and kidney damage induced by cisplatin. Wistar albino rats were divided into four groups: Control, Cisplatin (single dose of 7 mg/kg, intraperitoneal), Kefir (2 ml/d, 7 d, oral gavage), and Cisplatin+Kefir (CK). At the end of day 7, animals were euthanized. Blood, kidney, and liver tissue samples were collected. For both tissues, biochemically ALT, AST, Urea, Creatine; histomorphologically, hematoxylin-eosin, Masson's Trichrome, and immunohistochemical staining of caspase-3, a marker of apoptosis, were performed. Serum urea and creatinine levels of the Cisplatin group were significantly higher than the Control group (p<0.05). In the CK group, kefir consumption decreased urea and creatinin levels approached to Control and Kefir groups. Cisplatin resulted in higher ALT and AST activities, indicating hepatocellular damage, compared to the Control group (p<0.05). Kefir consumption decreased ALT activities approached to both the Control and Kefir group. Histomorphological observations were in agreement biochemical results. In liver and kidney tissues, structural damage was observed with an increase in collagen fibers in the Cisplatin group, and Caspase-3 activity was immunohistochemically higher than in the other groups. In the CK group, collagen fiber increase, structural damage, and Caspase-3 activities were less than in the Cisplatin group. Kefir consumption alleviated liver and kidney damage. However, more research is required to understand such effect of kefir better.

RESUMEN: El cisplatino es un agente quimioterapéutico que induce daño hepático y renal. En este estudio, intentamos investigar el efecto del kéfir, un alimento funcional y probiótico esencial, en el daño hepático y renal inducido por el cisplatino. Se dividieron ratas albinas Wistar en cuatro grupos: control, cisplatino (dosis única de 7 mg/kg, intraperitoneal), kéfir (2 ml/día, 7 días, sonda oral) y cisplatino + kéfir (CK). Al final del día 7, los animales fueron sacrificados. Se recolectaron muestras de sangre, riñón y tejido hepático. Se determinó ALT, AST, Urea y Creatina; Para el análisis histomorfológico, se realizaron tinciones con hematoxilina-eosina, tricrómico de Masson y para inmunohistoquímica, caspasa-3, un marcador de apoptosis. Los niveles séricos de urea y creatinina del grupo de cisplatino fueron significativamente más altos que los del grupo de control (p<0,05). En el grupo CK, el consumo de kéfir disminuyó los niveles de urea y creatinina acercándose a los grupos Control y Kéfir. El cisplatino resultó en actividades más altas de ALT y AST, lo que indica daño hepatocelular, en comparación con el grupo Control (p<0.05). El consumo de kéfir disminuyó las actividades de ALT tanto en el grupo Control como en el de Kéfir. Las observaciones histomorfológicas coincidieron con los resultados bioquímicos. En tejidos hepáticos y renales se observó daño estructural con aumento de fibras colágenas en el grupo de Cisplatino, y la actividad de Caspasa-3 fue inmunohistoquímicamente mayor que en los otros grupos. En el grupo de CK, el aumento de las fibras colágenas, el daño estructural y las actividades de Caspasa-3 fueron menores que en el grupo Cisplatino. El consumo de kéfir mejoró el daño hepático y renal. Sin embargo, se requiere más investigación para comprender mejor el efecto del kéfir.

Parámetros de laboratorio clínico en pacientes con la COVID-19 / Clinical laboratory parameters in patients with COVID-19

Introducción: Conocer las alteraciones en exámenes de laboratorio clínico, es de utilidad en el diagnóstico y el progreso de pacientes con la COVID-19. Objetivo: Describir los parámetros de laboratorio clínico en pacientes diagnosticados con la COVID-19. Métodos: Estudio descriptivo en 82 pacientes hospitalizados con la COVID-19. Las variables analizadas fueron edad, sexo, comorbilidad, reporte de paciente, estado al egreso, hemoglobina, recuento de glóbulos blancos, conteo absoluto de neutrófilos, conteo absoluto de linfocitos, conteo de plaquetas, eritrosedimentación, dímero D, creatinina, urea, alanina aminotransferasa, aspartato aminotransferasa, #947;-glutamil transpeptidasa, fosfatasa alcalina, lactato deshidrogenasa, relación neutrófilos/ linfocitos y de plaquetas/ linfocitos. Resultados: La edad promedio fue de 55,61 ± 22,04, fue mayoría el sexo femenino (57,3 por ciento), hipertensos (41,5 por ciento), el 18,3 por ciento reportados de grave y el 14,6 por ciento falleció. La edad avanzada y la comorbilidad se asociaron al reporte de gravedad. Hubo disminución significativa de la hemoglobina, linfocitos; elevación de la eritrosedimentación, dímero D, creatinina, #947;-glutamil transpeptidasa y lactato deshidrogenasa, sobre todo en graves. La relación neutrófilos/ linfocitos y de plaquetas/ linfocitos alertaron sobre el agravamiento del paciente y la posibilidad de fallecer. Conclusiones: Los pacientes tenían una media de edad de 55,61, del sexo femenino, con hipertensión arterial; egresaron vivos, reportados de no graves. Disminuyen los valores medios de hemoglobina, conteo global de los linfocitos, sobre todo en graves; aumenta el dímero D, creatinina, ALT, AST, ALP, GGT, y LD. La relación neutrófilos/ linfocitos y de plaquetas/ linfocitos muestran valores medios altos, sobre todo en graves y en quienes fallecieron (AU)

Introduction: Knowing the alterations in clinical laboratory tests is useful in the diagnosis and progress of patients with COVID-19. Objective: To describe the clinical laboratory parameters in patients diagnosed with COVID-19. Methods: Descriptive study in 82 hospitalized patients with COVID-19. The variables analyzed were age, sex, comorbidity, patient report, discharge status, hemoglobin, white blood cell count, absolute neutrophil count, absolute lymphocyte count, platelet count, erythrocyte sedimentation rate, D-dimer, creatinine, urea, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, alkaline phosphatase, lactate dehydrogenase, neutrophil / lymphocyte and platelet / lymphocyte ratio. Results: The average age was 55.61 ± 22.04, the majority were female (57.3 percent), hypertensive (41.5 percent), 18.3 percent reported serious and 14.6 percent died. Advanced age and comorbidity were associated with the severity report. There was a significant decrease in hemoglobin, lymphocytes; elevated erythrocyte sedimentation rate, D-dimer, creatinine, γ-glutamyl transpeptidase, and lactate dehydrogenase, especially in severe patients. The neutrophil / lymphocyte and platelet / lymphocyte ratio warned about the worsening of the patient and the possibility of death. Conclusions: The patients a mean age of 55.61, female, with arterial hypertension; they were discharged alive, reported as not serious. Mean hemoglobin values ​​decrease, global lymphocyte count, especially in severe patients; increases D-dimer, creatinine, ALT, AST, ALP, GGT, and LD. The neutrophil / lymphocyte and platelet / lymphocyte ratio show high mean values, especially in severely ill patients and in those who died(AU)

Silymarin's defensive role against hepatotoxicity induced by amiodarone in albino rats / El efecto defensivo de silimarin contra la hepatotoxicidad inducida por amiodarona en ratas albinas

SUMMARY: Amiodarone (AMD), an orally powerful antidysrhythmic medication that has caused hepatotoxicity on long-term administration, is commonly used across the world. Silymarin ameliorative effects (SLM); this research elucidated the magnitude of the damage to the liver tissue in AMD. We divided 24 albino rats evenly into four groups given daily doses by gastric tube for eight weeks as follows; the 1st group acted as a control group; the 2nd group received SLM; the 3rd group received AMD; and the 4th group received AMD parallel to SLM. Liver tissues prepared for light, electron microscopic and serum samples screened for biomarkers (I)liver injury enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST); (II) oxidative and antioxidant stress, malondialdehyde (MDA) and superoxide dismutase (SOD); and (III) inflammatory markers, tumor necrosis factor-alpha (TNF-a) and interleukin-6 (IL-6). The findings showed that AMD caused hepatic histological changes that included congestion of the blood vessels, leucocytic infiltration and cytoplasmic vacuolation. Ultrastructural degeneration of the mitochondria, endoplasmic reticulum swelling, nuclear pyknosis and increased fat droplets and lysosomes were observed. The biochemical findings showed an increase in the AMD group's ALT and AST activities. The group of rats treated with AMD and SLM, increased the improvements in histology and ultrastructure, while the ALT and AST levels were reduced. Our findings collectively agreed that SLM has a protective impact on AMD hepatotoxicity which can be due to its antioxidant properties.

RESUMEN: La amiodarona (AMD) es un fuerte medicamento antiarrítmico administrado por vía oral que ha causado hepatotoxicidad en la administración a largo plazo utilizado con frecuencia en todo el mundo. Efectos de mejora de la silimarina (SLM); esta investigación analizó la magnitud del daño al tejido hepático en la DMAE. Dividimos 24 ratas albinas de manera uniforme en cuatro grupos que recibieron dosis diarias por sonda gástrica durante ocho semanas de la siguiente manera; el primer grupo fue designado como grupo control; el segundo grupo recibió SLM; el tercer grupo recibió AMD; y el cuarto grupo recibió AMD en paralelo a SLM. Se prepararon tejidos hepáticos para muestras de suero, microscopía de luz y electrónica y se analizaron para biomarcadores (I) enzimas de daño hepático, alanina aminotransferasa (ALT) y aspartato aminotransferasa (AST); (II) estrés oxidativo y antioxidante, malondialdehído (MDA) y superóxido dismutasa (SOD); y (III) marcadores inflamatorios, factor de necrosis tumoral alfa (TNF-a) e interleucina-6 (IL-6). Los hallazgos mostraron que la DMAE genera cambios histológicos hepáticos que incluyen congestión de los vasos sanguíneos, infiltración leucocítica y vacuolación citoplásmica. Se observó una degeneración ultraestructural de las mitocondrias, aumento del retículo endoplásmico, picnosis nuclear y aumento de gotitas de grasa y lisosomas. Los hallazgos bioquímicos mostraron un aumento en las actividades de ALT y AST del grupo AMD. El grupo de ratas tratadas con AMD y SLM, aumentó las mejoras en histología y ultraestructura, mientras que se redujeron los niveles de ALT y AST. Nuestros hallazgos coincidieron colectivamente en que SLM tiene un impacto protector sobre la hepatotoxicidad de AMD debido a sus propiedades antioxidantes.

The effect of Farnesoid X receptor agonist tropifexor on liver damage in rats with experimental obstructive jaundice

ABSTRACT Purpose: To investigate experimentally the effects of Tropifexor, a farnesoid X receptor agonist, on liver injury in rats with obstructive jaundice. Methods: Forty healthy Wistar albino female rats were divided randomly in selected groups. These groups were the sham group, control group, vehicle solution group, Ursodeoxycholic acid group and Tropifexor group. Experimental obstructive jaundice was created in all groups, except the sham one. In the blood samples obtained, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), total bilirubin and direct bilirubin levels were established and recorded. Additionally, liver malondialdehyde, myeloperoxidase and catalase enzyme activity in the tissue samples were studied. Histopathological analysis was also performed. Results: No statistical difference was found between the control group and the Tropifexor group when AST, ALT and ALP values were compared. However, it was found that the Tropifexor group had statistically significant decreases in the values of GGT, total bilirubin and direct bilirubin (p < 0.05). Additionally, Tropifexor decreased the median values of malondialdehyde and myeloperoxidase, but this difference was not statistically significant compared to the control group. Finally, the Tropifexor group was statistically significant in recurring histopathological liver damage indicators (p < 0.05). Conclusions: Tropifexor reduced liver damage due to obstructive jaundice.

Paeoniflorin mitigates PBC-induced liver fibrosis by repressing NLRP3 formation

ABSTRACT Purpose: To delve into the influence of paeoniflorin (PA) on abating primary biliary cholangitis (PBC)-induced liver fibrosis and its causative role. Methods: Our team allocated the mice to control group, PA group, PBC group and PBC+PA group. We recorded the weight change of mice in each group. We used Masson staining for determining liver fibrosis, immunofluorescence staining for measuring tumor necrosis factor-α (TNF-α) expression, quantitative real-time polymerase chain reaction (qRT-PCR) for assaying related gene expression, as well as Western blot for testing related protein expression. Results: The weight of PBC model mice declined. Twenty-four weeks after modeling, the positive rate of anti-mitochondrial antibody-M2 (AMA-M2) in PBC mice reached 100%. Alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), hydroxyproline (HYP), laminin (LN), procollagen type III (PC III), and malondialdehyde (MDA) contents saliently waxed (p<0.01). Meanwhile, superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) activity patently waned (p<0.01). Liver fibrosis levels were flagrantly higher (p<0.01), and TNF-α, NOD-like receptor protein 3 (NLRP3), caspase-1, interleukin-18 (IL-18), and interleukin-1β (IL-1β) protein or gene expression were manifestly up-regulated (p<0.01). PA could restore the weight of PBC mice, strikingly restrain the positive expression of AMA-M2, and down-regulate serum ALP, ALT, AST, HYP, LN, PC III, MDA in PBC mice (p<0.01). PA could also significantly up-regulate SOD and GSH-px levels (p<0.01), down-regulate IL-1β, IL-18, caspase-1, NLRP3, and TNF-α protein or gene expression in PBC mice (p<0.01) and inhibit liver fibrosis levels (p<0.01). Conclusions: PA can reduce PBC-induced liver fibrosis in mice and may function by curbing the formation of NLRP3.

Hepatocellular Liver Function of Immunosuppressed Rats with Oral Candidiasis after Hyperbaric Oxygen Treatment: Alanine Transaminase and Aspartate Transaminase Levels

ABSTRACT@#Hepatocellular utility is observed by measuring the hepatocellular enzymes. Changes in its serum levels are related to liver dysfunction. Liver is one of the immunoprotective organs. Continuous use of immunosuppressive drugs can cause oral candidiasis and give effects to liver function. Hyperbaric oxygen treatment (HBOT), while reducing fungal infections, can also repair the liver function. The aim of this study was to investigate the alanine transaminase (ALT) and aspartate transaminase (AST) levels of immunosuppressed rats with oral candidiasis treated with hyperbaric oxygen. Twelve Wistar rats were divided into three groups: K− (normal/ healthy), K+ (oral candidiasis immunosuppressed rats), and P (oral candidiasis immunosuppressed rats treated hyperbaric oxygen). K+ and P groups were immunosuppressed by giving dexamethasone 0.5 mg/day/rat orally for 14 days, added with tetracycline 1 mg/day/rat. HBOT was given in five days successively. Blood serum of rats in all groups were taken to calculate the ALT and AST levels. ALT and AST levels in K+ showed higher value than K− and P groups. The data were analysed with one-way ANOVA test and showed significant difference in ALT levels (p < 0.05), while in AST levels there was no significant difference among the groups (p > 0.05). This study showed that HBOT affected the ALT and AST levels of immunosuppressed rats with oral candidiasis.

Análise do fêmur de ratas tratadas com ocitocina e submetidas ao treinamento de força durante a periestropausa / Analysis of the femur of rats treated with oxytocin and submitted to strength training during periestropause

A diminuição nas concentrações de estrógeno, como o que ocorre no período da perimenopausa e menopausa, contribui para o aumento do turnover ósseo, com taxa de reabsorção superior à de formação óssea que favorece a instalação da osteoporose, doença silenciosa que determina fragilidade óssea e maior probabilidade de fraturas. Entre as intervenções utilizadas para prevenção da osteoporose, destaca-se o treinamento de força (TF) e a ocitocina (OT), hormônio promissor com ação anabólica no osso. O objetivo deste estudo foi verificar a ação da associação da OT ao TF, em comparação às intervenções isoladas, no processo de remodelamento ósseo do colo do fêmur de ratas Wistar na periestropausa (18 a 21 meses). Quarenta ratas Wistar com ciclo estral irregular (18 meses) foram randomizadas nos grupos: 1- Veículo (Veh); 2-Ocitocina (Ot); 3-Treinamento de força (Tf); 4-Ot+Tf. Os animais do grupo 1 receberam salina (0,15 mol/L) e dos grupos 2 e 4 receberam OT (134 µg/kg), sendo duas injeções intraperitoneais com intervalo de 12 horas a cada 30 dias, totalizando 8 injeções ao final do período experimental. Os animais dos grupos 3 e 4 realizaram TF em escada 3 vezes por semana com realização mensal do teste de capacidade de carga máxima voluntária (CCMV). Após 120 dias, os animais foram eutanasiados, os fêmures foram coletados para análises de ensaio mecânico, densitometria, microtomografia óssea, espectroscopia de Raman e técnica de reação em cadeia da polimerase de transcrição reversa em tempo real (qRT-PCR), e o sangue para análises de marcadores bioquímicos do metabolismo ósseo, dano hepático e estresse oxidativo. A principal novidade deste estudo é a adição da OT ao TF, a qual apresentou, no ensaio de compressão, maior força máxima em relação ao Veh e menor elasticidade em relação ao Tf e, no ensaio de flexão de três pontos, maior rigidez em relação ao Veh e Ot, menor rigidez e menor elasticidade em relação ao Veh; maior espessura cortical (Ct.Th) em relação aos demais grupos, menor número de poros (Po.N) em relação ao Veh e Ot, e maior momento polar médio (J) em relação ao Tf. Houve também maior volume do osso trabecular (BV/TV) em relação ao Ot e maior espessura trabecular (Tb.Th) em relação aos demais grupos. A densidade mineral óssea areal (aDMO) do colo do fêmur foi maior que o Ot, e a DMO do fêmur total foi maior que os demais grupos. Quanto a expressão gênica, houve maior expressão do fator de transcrição relacionado ao Runt 2 (Runx2) em relação ao Veh, o fator de transcrição Osterix (Osx/Sp7) foi menor que o Ot e Tf. A proteína morfogenética óssea 2 (Bmp2) apresentou menor expressão em relação ao Veh, e a expressão da fosfatase alcalina óssea (Fal) foi maior que os demais grupos. A expressão do membro da família do fator de necrose tumoral 11b (Opg) e do ligante do fator de necrose tumoral (Rankl) foi maior que os outros grupos, a expressão do membro do fator de necrose tumoral 11a (Rank) e catepsina K (Ctsk) foi maior que Veh e Ot. Também foi observado menor atividade de fosfatase ácida resistente ao tartarato (TRAP) e capacidade antioxidante total (CAT) no ensaio bioquímico em relação aos demais grupos. Na intervenção com OT, houve maior elasticidade no ensaio de flexão de três pontos, e maior Ct.Th em relação ao Veh. A expressão gênica de Runx2, Osx/Sp7 foi maior e Bmp2 foi menor que o grupo Veh. No TF houve maior elasticidade que o Veh e Ot no ensaio de compressão, maior rigidez e elasticidade em relação ao Veh no ensaio de flexão de três pontos. Houve menor Ct.Th em relação ao Ot, maior DMO do fêmur total em relação ao Veh, e a taxa de mineralização foi maior que o Veh e Ot. Na expressão gênica, Runx2 e Osx/Sp7 foram maiores que o Veh. A Bmp2 e osteocalcina/proteína óssea gama-carboxiglutamato (Ocn) foram menores que o Veh, e a Fal foi menor que Ot. Em relação a Rank e Ctsk, estas foram maiores que Veh e Ot. Por fim, a atividade de aspartato aminotransferase (AST) foi menor que o Veh. Esses resultados mostraram que a associação de intervenções é estratégia anabólica promissora para a prevenção da osteoporose no período da periestropausa, destacando-se dos efeitos das intervenções isoladas, ao preservar aspectos mecânicos, estruturais e gênicos do osso, além de parecer controlar fatores relacionados ao cross-talk entre tecido ósseo e tecido adiposo a favor da homeostase oxidativa e de fatores relacionados a atividade de marcadores ósseos(AU)

The decrease in estrogen concentrations, such as that which occurs during perimenopause and menopause, contributes to an increase in bone turnover, with a rate of resorption higher than that of bone formation, which favors the installation of osteoporosis, a silent disease that determines bone fragility and greater probability of fractures. Among the interventions used to prevent osteoporosis, strength training (ST) and oxytocin (OT), a promising hormone with anabolic action on bone, stand out. The objective of this study was to verify the action of the association of OT and ST, compared to isolated interventions, in the process of bone remodeling of the femoral neck of Wistar rats in periestropause (18 to 21 months). Forty Wistar rats with irregular estrous cycle (18 months) were randomized into groups: 1-Vehicle (Veh); 2-Oxytocin (Ot); 3-Strength training (St); 4-Ot+St. The animals in group 1 received saline (0.15 mol/L) and in groups 2 and 4 received OT (134 µg/kg), with two intraperitoneal injections with an interval of 12 hours every 30 days, totaling 8 injections at the end of the period. trial period. The animals in groups 3 and 4 performed ST on a ladder 3 times a week with monthly performance of the maximum voluntary carrying capacity test (MVCC). After 120 days, the animals were euthanized, the femurs were collected for mechanical assay analysis, densitometry, bone microtomography, Raman spectroscopy and real-time reverse transcription polymerase chain reaction (qRT-PCR) technique, and blood for analysis of biochemical markers of bone metabolism, liver damage and oxidative stress. The main novelty of this study is the addition of OT to ST, which presented, in the compression test, greater maximum force in relation to Veh and less elasticity in relation to St and, in the three-point bending test, greater stiffness in relation to to Veh and Ot, less rigidity and less elasticity in relation to Veh; greater cortical thickness (Ct.Th) in relation to the other groups, smaller number of pores (Po.N) in relation to Veh and Ot, and greater mean polar moment (J) in relation to St. There was also greater trabecular bone volume (BV/TV) in relation to Ot and greater trabecular thickness (Tb.Th) in relation to the other groups. The areal bone mineral density (aBMD) of the femoral neck was higher than the Ot, and the BMD of the total femur was higher than the other groups. As for gene expression, there was greater expression of the transcription factor related to Runt 2 (Runx2) in relation to Veh, the transcription factor Osterix (Osx/Sp7) was lower than Ot and St. Bone morphogenetic protein 2 (Bmp2) showed lower expression compared to Veh, and boné alkaline phosphatase (Alp) expression was higher than the other groups. The expression of tumor necrosis factor 11b family member (Opg) and tumor necrosis factor ligand (Rankl) was higher than the other groups, tumor necrosis factor 11a member (Rank) and cathepsin K (Ctsk) was greater than Veh and Ot. It was also observed lower activity of tartrate resistant acid phosphatase (TRAP) and total antioxidant capacity (CAT) in the biochemical assay in relation to the other groups. In the intervention with OT, there was greater elasticity in the three-point bending test, and greater Ct.Th in relation to Veh. The gene expression of Runx2, Osx/Sp7 was higher and Bmp2 was lower than the Veh group. In ST intervention there was greater elasticity than Veh and Ot in the compression test, greater stiffness and elasticity in relation to Veh in the three-point bending test. There was lower Ct.Th in relation to Ot, higher BMD of the total femur in relation to Veh, and the mineralization rate was higher than Veh and Ot. In gene expression, Runx2 and Osx/Sp7 were higher than Veh. Bmp2 and osteocalcin/bone protein gammacarboxyglutamate (Ocn) were lower than Veh, and Fal was higher than Ot. In relation to Rank and Ctsk, these were higher than Veh and Ot. Finally, aspartate aminotransferase (AST) activity was lower than Veh. These results showed that the association of interventions is a promising anabolic strategy for the prevention of osteoporosis in the periestropause period, standing out from the effects of isolated interventions, by preserving mechanical, structural and genetic aspects of the bone, in addition to seeming to control factors related to the cross -talk between bone tissue and adipose tissue in favor of oxidative homeostasis and factors related to the activity of bone markers(AU)

Assessment of liver disease by non-invasive methods in perinatally infected Brazilian adolescents and young adults living with Human Immunodeficiency Virus (HIV)

ABSTRACT Introduction: Effective and long-term combined antiretroviral therapy (cART) has decreased morbidity and mortality in HIV-infected individuals. Despite treatment advances, HIV-infected children continue to develop noninfectious conditions, including liver fibrosis. Methods: Cross-sectional study designed to identify liver fibrosis in HIV-infected adolescents and young adults, in an outpatients clinic of Pediatric Infectious Diseases Division at Escola Paulista de Medicina/Universidade Federal de São Paulo (UNIFESP), diagnosed by noninvasive methods (liver elastography-FibroScan®, APRI and FIB4). Variables examined included demographics, clinical, laboratories, HIV treatment. All participants underwent FibroScan® to measure liver parenchyma elasticity. Values equal to above 7.0 kPa were interpreted as the presence of significant liver fibrosis. Two different biomarkers of liver fibrosis were employed: the AST-to-Platelet Ratio Index (APRI) and the Fibrosis-4 score (FIB-4). APRI values above 1.5 have been considered as levels of clinically significant liver fibrosis and FIB-4 values above 3.25 suggested the presence of advanced fibrosis. Results: Between August 2014 and March 2017, the study enrolled 97 patients, age 10-27 years old, fourteen of 97 subjects (14.4%) presented liver stiffness (≥7 kPa) detected by the liver elastography. No patient had APRI> 1.5. No patient had FIB4 value > 3.25. The only isolated laboratory parameter that could be significantly associated with high liver stiffness was thrombocytopenia (p= 0.022, Fisher's exact test). Conclusion: Liver stiffness was identified in 14.4% (14/97) of this cohort by liver elastography. Liver disease in HIV-infected adolescents and young adults manifests itself silently, so should be routinely investigated.

Células madre adiposas humanas disminuyen el daño de la fibrosis hepática con baja persistencia de células trasplantadas en ratas / Human adipose stem cells decrease liver fibrosis damage with low persistence of transplanted cells in rats

RESUMEN: En la enfermedad hepática crónica el trasplante ortotópico es la única alternativa terapéutica actual pero es limitada por falta de donantes. Ensayos con células madre adultas en daño hepático agudo evidencian promisorios resultados. El objetivo de este trabajo fue evaluar en ratas con daño hepático crónico la efectividad de la infusión de células madre adiposas humanas (CMAd-h). Ratas con fibrosis hepática inducida por tioacetamida fueron agrupadas en: grupo I control que no recibió tioacetamida ni células madre, grupo II recibió tioacetamida y suero fisiológico i.v., grupo III recibió tioacetamida y células madre adiposas 1 x 106/kg i.v. vía vena de la cola. La regeneración hepática histológica se evaluó por el index METAVIR, mientras las Macrophagocytus stellatus, células estrelladas a- SMA+ y células colágeno I+ por inmunohistoquímica; el daño funcional se evaluó por los niveles sanguíneos de los analitos Aspartato Aminotransferasa (AST), Alanina Aminotransferasa (ALT), Fosfatasa Alcalina (ALP), úrea y nitrógeno ureico (BUN) y hemograma. Los resultados muestran atenuación del daño estructural hepático evidenciado por disminución de los nódulos, del grado de lesión histológica en el score Metavir, y disminución de Macrophagocytus stellatus, células a-SMA+ y células colágeno tipo I+; funcionalmente hay reducción moderada de AST, ALT, urea, BUN y disminución moderada de células blancas pero efecto favorable sobre el volumen corpuscular media y la hemoglobina corpuscular media. Ocho semanas después de la infusión hay escasa población de CMAd-h en el hígado. En conclusión la infusión intravenosa de CMAd-h en ratas disminuye el daño funcional y estructural de la fibrosis hepática con escasa persistencia de CMAd-h en el parénquima hepático. A nuestro conocimiento este es el primer trabajo que evalúa el efecto de las CMAd-h en el modelo daño hepático crónico murino y la persistencia de las células trasplantadas.

SUMMARY: In chronic liver disease, orthotopic transplantation is the only current therapeutic alternative but it is limited due to lack of donors. Trials with adult stem cells in acute liver damage show promising results. The aim of this work was to evaluate the effectiveness of human adipose stem cell (h-ASC) infusion in rats with chronic liver damage. Rats with thioacetamide- induced liver fibrosis were grouped into: group I control that did not receive thioacetamide and h-ASC, group II received thioacetamide and saline i.v., group III received thioacetamide and h-ASC 1 x 106/ kg i.v. via tail vein. Histological liver regeneration was evaluated by METAVIR index, while Macrophagocytus stellatus (Kupffer cells), stellate cells a-SMA+ and collagen I+ cells by immunohistochemistry; functional damage was evaluated by blood levels of the analytes Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Urea and Blood Urea Nitrogen (BUN) and hemogram. The results show attenuation of structural liver damage evidenced by decreased nodules, degree of histologic injury on Metavir score, and decreased Macrophagocytus stellatus, a-SMA+ cells and type I+ collagen cells; functionally there is moderate reduction of AST, ALT, urea, BUN and moderate decrease of white cells but favorable effect on mean corpuscular volume and mean corpuscular hemoglobin. Eight weeks after infusion there is a small population of h-ASC in the liver. In conclusion, intravenous infusion of h-ASC in rats reduces functional and structural damage of hepatic fibrosis with low persistence of h- ASC in the liver parenchyma. To our knowledge this is the first work that evaluates the effect of h-SC in the model of chronic murine liver damage and the persistence of transplanted cells.

¿Son los criterios de la ASGE suficientes para la estratificación del riesgo de coledocolitiasis? / ¿Are the ASGE criteria sufficient to stratify the risk of choledocholithiasis?

Resumen Introducción: la patología biliar litiásica es una de las entidades más frecuentes en el área de cirugía general y en gastroenterología. El tratamiento varía según el lugar donde se alojen los cálculos. Para esto, se han definido diversas escalas de estratificación del riesgo de presentar coledocolitiasis, pero son los criterios planteados por la Sociedad Americana de Endoscopia Gastrointestinal (American Society for Gastrointestinal Endoscopy, ASGE) los más usados a nivel mundial, ya que tienen una precisión diagnóstica definida del 70 %. Los procedimientos o ayudas diagnósticas establecidas por estos criterios, en ocasiones, prolongan el tiempo de hospitalización, aumentan los costos y pueden tener complicaciones. Metodología: se realizó un estudio observacional analítico, de tipo transversal retrospectivo, con datos obtenidos a partir de las historias clínicas de pacientes sometidos a colecistectomía laparoscópica, en la Clínica CES de Medellín, entre julio y diciembre de 2017. Resultados y conclusiones: se analizaron 424 historias clínicas de pacientes sometidos a colecistectomia laparoscópica. De ellos, 254 (56,76 %) se categorizaron como de riesgo bajo, mientras que 94 (22,11 %) fueron de riesgo intermedio y 76 (17,88 %) de riesgo alto. Se encontró una frecuencia de coledocolitiasis del 90,8 % en aquellos categorizados como de riesgo alto y del 26,6 % en los pacientes de riesgo intermedio. En la categoría de riesgo intermedio se hallaron diferencias estadísticamente significativas entre ambos grupos para los valores de bilirrubina total, bilirrubina directa y aspartato aminotransferasa (AST) (p = 0,001; p = 0,014; p = 0,007, respectivamente). La baja frecuencia de coledocolitiasis en la categoría de riesgo intermedio puede ser explicada por cálculos menores a 5 mm no visibles en la colangiorresonancia. A partir de este estudio, se propone ajustar los rangos de valores de los criterios de la ASGE para la categoría de riesgo intermedio, permitiendo tener una mayor precisión a la hora de clasificar los pacientes con patología litiásica y disminuir costos y estancia hospitalaria.

Abstract Introduction: Biliary lithiasis is one of the most frequent diseases in the area of general surgery and gastroenterology. Treatment varies depending on the location of the gallstones. Several stratification scales of the risk of choledocholithiasis have been defined, being the criteria proposed by the American Society of Gastrointestinal Endoscopy (ASGE) the most used worldwide, with a diagnostic accuracy of 70%. However, the procedures or diagnostic aids defined by these criteria, sometimes, increase hospital stay, costs, and may lead to the development of complications. Methodology: An observational, analytical, retrospective, cross-sectional study was conducted with data obtained from the clinical records of patients undergoing laparoscopic cholecystectomy at the CES Clinic in Medellín, Colombia, between July and December of 2017. Results and conclusions: 424 medical records were analyzed, of which 254 (56.76%) were classified as low-risk, 94 (22.11%) as intermediate-risk and 76 (17.88%) as high-risk. The frequency of choledocholithiasis was 90.8% in high-risk patients and 26.6% in intermediate-risk patients. For the intermediate-risk category, statistically significant differences were found between the two groups for the total bilirubin, direct bilirubin, and AST values (p: 0.001, p: 0.014, p:0.007, respectively). The low frequency of choledocholithiasis in the intermediate-risk category can be explained by less than 5mm gallstones not identified by the cholangioresonance. Based on this study, we propose to adjust the ranges of the ASGE criteria variables for the intermediate-risk category for better accuracy when classifying patients with biliary lithiasis and, thus, reduce costs and hospital stay.

Suspensão oral de rutina interfere na hiperplasia hepática em ratos / Oral rutin suspension intervene in hepatic hyperplasia in rats

ABSTRACT BACKGROUND: Rutin is a flavonol glycoside that can be found in a wide variety of vegetables and has activity, anti-cancer, anti-inflammatory and anti-diabetic properties. OBJECTIVE: This study investigated the effect of rutin oral administration on Wistar rats submitted to hepatic hyperplasia after partial hepatectomy (PH). METHODS: To achieve this, we considered the analysis of hepatic hyperplastic and plasma biochemical activity of Wistar rats, subjected to treatment with rutin 40 mg/kg/day for 10 days in group 1 (G1) or saline in group 2 (G2), followed by partial hepatectomy. RESULTS: The results indicated an increase in the number of mitoses after 24 hours and 48 hours (P=0.0022 and P=0.0152, respectively) of PH in the group that received rutin, as well as an increase in AST serum levels after 24 hours (P=0.0159) and 48 hours (P=0.0158) and alkaline phosphatase after 24 hours (P=0.015) in the same group, in relation to the respective controls. The group that received rutin showed a more evident variation than the control group when comparing the 24 hour and 48 hour results regarding AST, number of mitoses and number of apoptosis (P<0.005). CONCLUSION: It was concluded that rutin intervened in hepatic hyperplasia after 24 hours and 48 hours of PH, favoring hepatic hyperplasia.

RESUMO CONTEXTO: A rutina é um flavonoide que pode ser encontrado em grande variedade de vegetais e apresenta atividades anticâncer, anti-inflamatória e antidiabética. OBJETIVO: O objetivo deste estudo foi investigar o efeito da administração oral de rutina sobre a hiperplasia hepática em ratos Wistar submetidos à hepatectomia parcial. MÉTODOS: Foi realizada a análise da hiperplasia hepática e da bioquímica plasmática dos ratos Wistar tratados com rutina 40 mg/kg por 10 dias no grupo 1 (G1) ou salina no grupo 2 (G2), seguido da hepatectomia parcial. RESULTADOS: Os resultados indicaram aumento do número de mitoses após 24 e 48 horas (P=0,0022 e P=0,0152, respectivamente) da hepatectomia parcial no grupo que recebeu rutina, além de um aumento nos níveis séricos de AST após 24 horas (P=0,0159) e 48 horas (P=0,0158) e de fosfatase alcalina após 24 horas (P=0,015) no mesmo grupo, em relação aos respectivos controles. O grupo que recebeu rutina mostrou variação mais evidente do que o grupo controle quando se comparou os resultados de 24 horas e 48 horas em relação a AST, número de mitoses e número de apoptoses (P<0,005). CONCLUSÃO: Foi possível concluir que a rutina interferiu na hiperplasia hepática após 24 e 48 horas após a hepatectomia parcial, favorecendo a hiperplasia hepática.