Aspartate Aminotransaminase Levels Research Articles

Intervention effect of Erchen Decoction on methionine and choline deficient diet-induced non-alcoholic steatohepatitis in mice

This study investigated the effect of Erchen Decoction(ECD) on the prevention of non-alcoholic steatohepatitis(NASH) in mice and explored its possible mechanism, so as to provide scientific data for the clinical application of ECD in the prevention of NASH. C57BL/6 male mice were randomly divided into normal group(methionine and choline supplement, MCS), model group(methionine and choline deficient, MCD), low-dose ECD group(ECD＿L, 6 g·kg~(-1)), medium-dose ECD group(ECD＿M, 12 g·kg~(-1)), and high-dose ECD group(ECD＿H, 24 g·kg~(-1)), with eight mice in each group. The MCS group was fed with an MCS diet, and the other groups were fed with an MCD diet. The mice in each group were given corresponding diets, but the drug intervention group was given low-, medium-, and high-dose ECD(10 mL·kg~(-1)·d~(-1)) by intragastric administration for six weeks on the basis of MCD diet feeding, and the mice could eat and drink freely during the whole experiment. At the end of the experiment, mice were fasted overnight(12 h) and were anesthetized with 20% urethane. Thereafter, the blood and liver tissue were collected. The serum was used to detect the levels of alanine aminotransferase(ALT), aspartate aminotransaminase(AST), interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α). Liver tissue was processed by hematoxylin-eosin(HE) staining and used for hepatic histological analysis and detection of the expression levels of genes and proteins related to nuclear factor erythroid 2-related factor 2/glutathione peroxidase 4(Nrf2/GPX4) pathway by real-time quantitative reverse transcriptase-polymerase chain reaction(RT-qPCR) and Western blot analysis, respectively. The results showed that compared with the MCS group, the MCD group showed higher serum ALT and AST levels; the HE staining exhibited fat vacuoles and obvious inflammatory cell infiltration in liver tissue; serum IL-1β, IL-6, and TNF-α levels were significantly increased, and the serum IL-10 level was significantly decreased. The mRNA expressions of fatty acid synthase(FASN), monocyte chemoattractant protein-1(MCP-1), and IL-1β in liver tissue were significantly up-regulated, while those of GPX4, Nrf2, and NAD(P)H:quinine oxidoreductase(NQO1) were significantly down-regulated. Compared with the MCD group, the serum ALT and AST levels of ECD＿M and ECD＿H groups were significantly decreased, and the AST level in the ECD＿L group was significantly decreased. The number of fat vacuoles and the degree of inflammatory cell infiltration in liver tissue were improved; serum IL-1β, IL-6, and TNF-α levels were significantly decreased, but the serum IL-10 level was significantly increased only in the ECD＿H group. The mRNA expressions of FASN, MCP-1, and IL-1β in liver tissue were significantly down-regulated, and those of GPX4 and NQO1 were significantly up-regulated. The mRNA expressions of Nrf2 in ECD＿M and ECD＿H groups were significantly up-regulated. Western blot results showed that compared with the MCD group, the protein expression levels of Nrf2 and GPX4 in each group were significantly increased after ECD administration, and the protein expression level of FASN was significantly decreased; the protein expression of NQO1 was increased in ECD＿M and ECD＿H groups. In summary, ECD can reduce hepatic lipid accumulation, oxidative stress, liver inflammation, and liver injury in NASH mice, which may be related to the activation of the Nrf2/GPX4 pathway.

Fatal outcome of a corticosteroid resistant IgG4-related autoimmune hepatitis and IgG4-primary sclerosing cholangitis.

33-year-old woman, previously hospitalized for self-limited migratory bile duct strictures, presented with jaundice three months after giving birth. Blood analysis revealed elevated levels of aspartate aminotransaminase 1064U/L, alanine aminotransaminase 1097U/L, gamma-glutamyl transferase 194U/L, alkaline phosphatase 284U/L, bilirubin 27mg/dL and prothrombin time of 19.3s. Magnetic resonance-cholangiopancreatography revealed intrahepatic bile duct dilation with a stenosis in the common hepatic duct, not detected on endoscopic retrograde cholangiopancreatography. Additionally, diffuse signal abnormalities were observed in the liver parenchyma on T2 sequences. An early liver biopsy showed moderate-severe interface hepatitis with IgG4-positive plasma cell infiltration (IgG4-PPC) of 8-20cells/HPF, hepatocellular ballooning and focal rosette formation, yielding 6 points of the simplified-score for autoimmune hepatitis and treatment with methylprednisolone was initiated. Despite treatment, there was no improvement after two weeks and the patient received rituximab as a rescue treatment, but three days later, developed candida sepsis with rapid progression to multiorgan failure, ultimately resulting in death.

High Density Lipoprotein Subfraction Changes in End Stage Liver Failure

BACKGROUND: This work was designed to ascertain high-density lipoprotein (HDL) subfractions and HDL-related enzyme alterations in end stage liver failure (ESLF). METHODS: Twenty patients with ESLF and twenty control subjects (liver donors) were chosen for the study. Before the transplant, serum samples from each patient and control were evaluated. Continuous disc polyacrylamide gel electrophoresis was performed to determine HDL subfraction changes and ELISA was carried out to determine serum levels of lecithin–cholesterol acyltransferase (LCAT), apolipoprotein A-1 (ApoA-I) and cholesteryl ester transfer protein (CETP). RESULTS: Liver failure patients had significantly higher levels of triglycerides (TG) and very low-density lipoprotein (VLDL) compared to healthy donors. Additionally, these patients showed significant increases in levels of aspartate aminotransaminase (AST), alkaline phosphatase (ALP), alanine aminotransaminase (ALT), and blood urea nitrogen (BUN), while albumin was notably lower compared to controls. Even though HDL cholesterol concentrations were not considerably altered between the two groups, ESLF patients had a marked raise in the HDL-large subfraction and a significant decline in the HDL-small subfraction in contrast to controls. Moreover, liver failure patients had considerably lower serum ApoA1 levels compared to healthy controls, but there was no significant difference in LCAT and CETP levels between the two groups. CONCLUSION: HDL subfraction profile can distinguish between healthy donors and liver failure patients. The results also indicate that levels of ApoA-1, which performs a crucial function in HDL metabolism, are lower in ESLF. This decrease in HDL-small subfractions may be due to impaired anabolism resulting from hepatic failure.

Association of Serum Cholinesterase and Liver Enzymes with Clinical Severity and Outcomes in Organophosphorus Poisoning

Abstract Background: Organophosphorus (OP) compound poisoning is a medico-toxic emergency that results in multiorgan failure. The primary mechanism of action is by inhibition of acetylcholinesterase, leading to disruption in processes of oxidative stress, apoptosis, and microsomal metabolism resulting in liver toxicity. The present study was conducted to explore the prognostic value of serum cholinesterase in predicting severity of organophosphorous compound poisoning and the need for ventilatory support; and to understand the role of aspartate aminotransaminase (AST), alanine aminotransaminase (ALT) and bilirubin in assessing the severity of acute organophosphate poisoning. Methodology: Hospital-based prospective observational study was conducted among OP poisoning cases at a tertiary hospital in Hubli. Clinical examination was done during the initial resuscitation and treatment of patients. Three milliliter of plain blood was collected on admission before administration of atropine and plasma cholinesterase level, and other biochemical parameters were estimated. Results: Sixty-five percent of poisoning cases had >50% of cholinesterase activity with normal grade poisoning. Moderate and severe grade poisonings were present among 3% and 5% of poisoning cases, respectively. Patients with cholinesterase level activity of ≤50% had significantly higher proportions of respiratory failure (77%) and fatal outcomes (33%). Median levels of AST (Q2: 73.2 IU/mL) and ALT were significantly higher (Q2: 22.7 IU/L) among severe grade poisoning (Che: <10%) compared to other grades of poisoning. Conclusion: The assessment of cholinesterase level activity in OP poisoning would be a useful guide to the physician for planning of intensive care, duration of hospital stay, and clinical prognosis. Serum AST and ALT levels can also contribute as supportive biomarkers to assess the severity, chances of respiratory failure, and clinical outcomes of OP poisoning.

KEYNOTE-365 cohorts E and F: Phase 1b/2 study of pembrolizumab + lenvatinib combination therapy in patients with adenocarcinoma metastatic castration-resistant prostate cancer (mCRPC) or treatment-emergent neuroendocrine mCRPC (t-NE).

TPS215 Background: Standard of care for noncurative adenocarcinoma mCRPC is docetaxel or the next-generation hormonal agents (NHAs) abiraterone and enzalutamide. However, approximately 20% of patients develop t-NE after treatment for adenocarcinoma mCRPC; t-NE is associated with shorter survival, and it has no standard of care beyond combination platinum chemotherapy. The vascular endothelial growth factor (VEGF)/fibroblast growth factor receptor (FGFR) inhibitor lenvatinib inhibits proliferation and angiogenesis in preclinical models of adenocarcinoma prostate cancer. The phase 2 KEYNOTE-199 trial showed some antitumor activity with pembrolizumab monotherapy in docetaxel-pretreated patients with adenocarcinoma mCRPC. VEGF/FGFR inhibition combined with PD-1 inhibition may have enhanced benefit in mCRPC, for adenocarcinoma and possibly as a new treatment option for t-NE. Methods: KEYNOTE-365 (NCT02861573) is a nonrandomized, open-label, multicohort, phase 1b/2 trial designed to evaluate different pembrolizumab combination therapies in several patient populations with mCRPC. Cohort E will enroll patients with confirmed adenocarcinoma of the prostate without small cell histology, per investigator. Cohort F will enroll patients with t-NE (≥1% neuroendocrine cells in a recent biopsy specimen confirmed by central histology review). Each cohort will include patients who previously received docetaxel treatment for mCRPC. Prior treatment with ≤2 NHAs (for hormone-sensitive metastatic prostate cancer [mHSPC] or mCRPC) and 1 other chemotherapy for mCRPC is permitted. Additionally, enrollment in cohort F requires prostate cancer progression within 6 months of starting an NHA (for mHSPC or mCRPC) and within < 6 cycles of docetaxel for mCRPC. Each cohort will enroll 40-100 patients with Eastern Cooperative Oncology Group performance status score of 0 or 1. Both cohorts will receive pembrolizumab 200 mg IV every 3 weeks + oral lenvatinib 20 mg once daily until disease progression, withdrawal of consent, prespecified alanine aminotransaminase or aspartate aminotransaminase level increase, or other discontinuation event. Primary end points are safety and tolerability, prostate-specific antigen (PSA) response rate, and objective response rate (ORR) per RECIST v1.1 by blinded independent central review (BICR). Secondary end points include time to PSA progression; ORR and radiographic progression-free survival per Prostate Cancer Working Group 3 (PCWG3)–modified RECIST v1.1 by BICR; duration of response and disease control rate per RECIST v1.1 and PCWG3-modified RECIST v1.1 by BICR; and overall survival. These cohorts of KEYNOTE-365 are enrolling in Australia, Germany, New Zealand, Spain, and the United States. Clinical trial information: NCT02861573.

Plasma exchange therapy for acute necrotizing encephalopathy of childhood.

ABSTRACTImportanceAcute necrotizing encephalopathy (ANE) is a rare disease with high mortality. Plasma exchange (PLEX) has recently been reported to treat ANE of childhood (ANEC), but its efficacy is uncertain.ObjectiveThis study aimed to investigate the effectiveness of PLEX on ANEC.MethodsA retrospective study was conducted in four pediatric intensive care units from December 2014 to December 2020. All patients who were diagnosed with ANEC were included; however, these patients were excluded if their length of stay was less than 24 h. Participants were classified into PLEX and non‐PLEX groups.ResultsTwenty‐nine patients with ANEC were identified, 10 in the PLEX group and 19 in the non‐PLEX group. In the PLEX group, C‐reactive protein, procalcitonin, alanine aminotransferase, and aspartate aminotransaminase levels were significantly lower after 3 days of treatment than before treatment (13.1 vs. 8.0, P = 0.043; 9.8 vs. 1.5, P = 0.028; 133.4 vs. 31.9, P = 0.028; 282.4 vs. 50.5, P = 0.046, respectively). Nine patients (31.0%, 9/29) died at discharge, and a significantly difference was found between the PLEX group and non‐PLEX group [0 vs. 47.4% (9/19), P = 0.011]. The median follow‐up period was 27 months, and three patients were lost to follow‐up. Thirteen patients (50.0%, 13/26) died at the last follow‐up, comprising three (33.3%, 3/9) in the PLEX group and ten (58.8%, 10/17) in the non‐PLEX group, but there was no significant difference between the two groups (P = 0.411). Three patients (10.3%, 3/29) fully recovered.InterpretationPLEX may reduce serum C‐reactive protein and procalcitonin levels and improve liver function in the short term. PLEX may improve the prognosis of ANEC, and further studies are needed.

Lipidomics reveals that acupuncture modulates the lipid metabolism and inflammatory interaction in a mouse model of depression

Depression is a serious disease that has considerable impact on lipid metabolism and inflammatory responses. Recent studies have shown that leptin, which is well known as a mediator of energy homeostasis and is a cytokine in inflammatory response, plays an important role in depression. Acupuncture is widely used to treat depression; however, the underlying mechanisms and the effect of acupuncture on depression remain poorly understood.In this study, we utilized the chronic restraint stress (CRS) induced depression model and acupuncture treatment was performed at KI10, LR8, LU8, LR4 (AP) or non-acupoint (NP). Then, lipidomics was applied to investigate the effects of acupuncture on lipid metabolism and analyze leptin signals in the brain and changes of immune markers.Acupuncture treatment at AP improved depression-like behavior in an open-field test, forced swimming test, and marble burying test. Concurrently, CRS mice treated with AP acupuncture (CRS + AP) had significantly lower levels of aspartate aminotransaminase (AST, liver injury markers) and exhibited different lipid patterns in liver lipidomic profiles. In particular, triglycerides (TGs) contributed the change of lipid patterns. Compared to the CRS mice, TGs with relatively high degrees of unsaturated fatty acids increased in the CRS + AP mice, but did not change in CRS mice treated with NP acupuncture (CRS + NP). The levels of leptin in plasma and leptin receptor positive cells in the brain (hypothalamus and hippocampus) decreased and increased, respectively, in the CRS + AP mice, while opposite patterns were exhibited in the CRS and CRS + NP mice. These results indicated that acupuncture treatment at AP attenuated leptin insensitivity in CRS mice. Additionally, expression of pro-inflammatory cytokines such as interleukin-1 beta and tumor necrosis factor-alpha were decreased in the spleen, plasma, and liver of CRS + AP mice, which was one of results of alleviation of leptin resistance. In conclusion, these results show that AP acupuncture treatment effectively alleviated the depression-like behavior, affected immune responses, and altered hepatic lipid metabolism through the attenuation of leptin insensitivity.

The AST/ALT (De Ritis) Ratio Predicts Survival in Patients with Oral and Oropharyngeal Cancer.

Aminotransaminases, including aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT), are strongly involved in cancer cell metabolism and have been associated with prognosis in different types of cancer. The purpose of the present study was to evaluate the prognostic significance of the pre-treatment AST/ALT ratio in a large European cohort of patients with oral and oropharyngeal squamous cell cancer (OOSCC). Data from 515 patients treated for OOSCC at a tertiary academic center from 2000–2017 were retrospectively analyzed. Levels of AST and ALT were measured prior to the start of treatment. Uni- and multivariate Cox regression analyses were applied to evaluate the prognostic value of the AST/ALT ratio for cancer-specific survival (CSS) and overall survival (OS), survival rates were calculated. Univariate analyses showed a significant association of the AST/ALT ratio with CSS (hazard ratio (HR) 1.71, 95% confidence interval (CI) 1.38–2.12; p < 0.001) and OS (HR 1.69, 95% CI 1.41–2.02; p < 0.001). In multivariate analysis, the AST/ALT ratio remained an independent prognostic factor for CSS and OS (HR 1.45, 95% CI 1.12–1.88, p = 0.005 and HR 1.42, 95% CI 1.14–1.77, p = 0.002). Applying receiver operating characteristics (ROC) curve analysis, the optimal cut-off level for the AST/ALT ratio was 1.44, respectively. In multivariate analysis, an AST/ALT ratio > 1.44 was an independent prognostic factor for poor CSS and OS (HR 1.64, 95% CI 1.10–2.43, p = 0.014 and HR 1.55, 95% CI 1.12–2.15; p = 0.008). We conclude that the AST/ALT ratio is a prognostic marker for survival in OOSCC patients and could contribute to a better risk stratification and improved oncological therapy decisions.

HEPATOPROTECTIVE EFFECT OF N-MIRACLE (POLYHERBAL FORMULATION) AGAINST ETHANOL INDUCED TOXICITY IN MALE ALBINO RATS

Objective: The aim of this current study is to investigate the hepatoprotective efficacy of N-Miracle (a polyherbal formulation) against ethanol-induced toxicity in male albino rats.&#x0D; Methods: Male Wistar albino rats weighing 150-200 g were used for the study. A total of 30 male albino rats were selected, divided into five groups. Ethanol-induced liver damage was done on Group III, IV, and V. Group I and Group II served as a normal and drug (N-Miracle) control. After the treatment period, the rats were anaesthetized by light ether anesthesia in a lethal chamber. Hepatic biomarkers, antioxidant enzymes, histopathological examination are carried out to document the hepatoprotective effect of N-Miracle (Polyherbal formulation).&#x0D; Results: The results of the present study demonstrated a significant (p&lt;0.05) increase in the levels of Aspartate Aminotransaminase (AST), Alanine Aminotransaminase (ALT) and Alkaline Phosphatase (ALP) in ethanol-induced rats as compared to normal and drug control Groups. The level of total protein and albumin were significantly (p&lt;0.05) decreased in ethanol-treated rats. The toxic impact of ethanol was found to be restored in rats treated with N-Miracle (Polyherbal formulation). The present study also exhibited the enzymatic antioxidant efficacy of N-Miracle (Polyherbal formulation) against ethanol-induced toxicity in rats by increasing the antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase and decreasing the activity of Glutathione-S-transferase in the liver. The findings are also correlated with histopathological examination of N-Miracle treated group, which shows hepatic regeneration and decrease in degradation of hepatocytes.&#x0D; Conclusion: This study could provide a possible explanation to hepatotoxicity resulting from exposure to ethanol. The findings of the present study revealed the ameliorative effect of N-Miracle (Polyherbal formulation) against ethanol-induced hepatotoxicity by improving the liver function, increasing the levels of antioxidant enzymes and restoring the morphological features of the liver.

Association of soluble interleukin-2 receptor alpha with laboratory parameters and clinical findings of hemophagocytic lymphohistiocytosis patients: The first report from South of Iran.

INTRODUCTION:Hemophagocytic lymphohistiocytosis (HLH) is caused by overactivation of immune system. Gene mutations, infections, malignant, and autoimmune trigger the development of the disease.MATERIALS AND METHODS:Clinical data and peripheral blood samples of 21 patients suspected of HLH were collected in Shiraz Medical Centers 2017–2018. Peripheral blood samples were analyzed for soluble interleukin-2 receptor alpha (sIL2Rα) marker (sCD25), and the results were compared with 36 normal controls as well as comparison with clinical findings and other laboratory parameters.RESULTS:Twenty-one patients (11 males and 10 females) with an average age of 5.2 were investigated. In this study, peripheral blood samples were taken from 16 newly diagnosed patients before treatment, and five were posttreatment blood samples. The mean sIL2Rα level before treatment in 16 patients was 9023 pg/ml. The mean peripheral blood sample of the 36 controls was 3025 pg/ml. The mean of the five posttreatment samples was 4198 pg/ml. Significant difference between pretreatment and the control group was observed. However, no significant difference was detected between after treatment samples and the control group. By comparing the sIL2Rα levels between patients with increased aspartate aminotransaminase (AST) and patients with normal AST level, there was a significant difference in the amount of IL2Rα level.CONCLUSION:This study highlights the importance of IL2Rα marker in the diagnosis and follow-up, during treatment and suppression. Furthermore, a significant difference with respect to AST level requires further investigation.

Predicting IVIg Nonresponse in Children With Kawasaki Disease

Research Article| January 01 2020 Predicting IVIg Nonresponse in Children With Kawasaki Disease AAP Grand Rounds (2020) 43 (1): 8. https://doi.org/10.1542/gr.43-1-8 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Predicting IVIg Nonresponse in Children With Kawasaki Disease. AAP Grand Rounds January 2020; 43 (1): 8. https://doi.org/10.1542/gr.43-1-8 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search toolbar search search input Search input auto suggest filter your search All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: immunoglobulins, intravenous, kawasaki's disease Source: Hester GZ, Watson D, Nickel AJ, et al. Identifying patients with Kawasaki disease safe for early discharge: development of a risk prediction model at a US children’s hospital. Hosp Pediatr. 2019; 9(10): 749– 756; doi: https://doi.org/10.1542/hpeds.2019-0049Google Scholar Investigators from multiple institutions conducted a retrospective study to develop a model for predicting which children with Kawasaki disease (KD) will be IV immunoglobulin (IVIg) nonresponders in hopes of identifying low-risk patients who could be discharged from the hospital earlier after receiving an initial dose of IVIg. Study participants were children 0–18 years old with a primary diagnosis of KD and hospitalized at a single, large, urban US children’s hospital. The medical records of study participants were reviewed, and clinical and laboratory data abstracted. The primary study outcome was IVIg nonresponse defined by one or more of the following criteria: (a) documented fever (temperature ≥38.0°C) 36 hours to 7 days after completion of IVIg dose, (b) receipt of a second dose of IVIg ≥20 hours after first dose, or (c) readmission within 7 days for the second dose of IVIg. Candidate clinical and laboratory parameters for inclusion in the prediction model were chosen, and backward stepwise regression was used to develop the final model, with only variables statistically associated with IVIg nonresponse (defined as P<.157) included. The concordance index (area under the receiver operator curve) was used to assess the accuracy of the final model after adjusting for over-optimism. Based on the model, the authors used a cutoff value for estimate of nonresponse of 10% and computed the sensitivity, specificity, and positive and negative predictive value (PPV and NPV) of the model for predicting IVIg nonresponse. Data on 430 children with KD who received an initial dose of IVIg were analyzed. A total of 81 (19%) met criteria for IVIg nonresponse. Variables included in the prediction model for IVIg nonresponse included white blood cell count, platelet count, hemoglobin, aspartate aminotransaminase level, serum sodium, serum albumin, maximum temperature 0–6 hours after IVIg, and presentation with classic KD (ie, fever for ≥5 days with at least 4 of 5 clinical features) versus incomplete KD. The adjusted concordance index of the model was 0.70. Using a cutoff value for predicted nonresponse of 10%, the model had a sensitivity of 90.1%, specificity of 30.1%, PPV of 23.0%, and NPV of 92.9%, with 26.3% of study participants classified as low risk. The authors conclude that a model combining clinical and laboratory parameters can be used to predict risk of IVIg nonresponse, and that this model can be used in identifying children who might be discharged sooner after an initial dose of IVIg. Dr Brady has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device. KD is the most common cause of acquired heart disease in children in developed countries.1 The incidence of KD... You do not currently have access to this content.

Oxidative stress, hematological and biochemical alterations induced by sub-acute exposure to fipronil (COACH®) in albino mice and ameliorative effect of selenium plus vitamin E.

Fipronil (FIP) is a highly effective, broad-use insecticide that belongs to the phenylpyrazole chemical group. It is extensively used in the agriculture and veterinary medicine for controlling a wide variety of pests. Though FIP showed lower toxicity in vertebrates than in insects, it was recognized to have a variety of toxic effects in mammals. The present study was undertaken to evaluate FIP-induced alterations in the blood biochemical markers and oxidative stress parameters in male albino mice via oral sub-acute toxicity exposure. The possible ameliorative effect of the pretreatment with selenium plus α-tocopherol (vitamin E) against the harmful effects of FIP was also investigated. Mice in FIP-test groups were exposed to different sublethal doses, i.e., 1.43, 2.87, and 4.78 mg active ingredient (AI)/kg body weight (b.w.), equal to 1/100, 1/50, and 1/30 LD50 of FIP, respectively, for 28 days. Mice in the amelioration groups were orally administered with selenium + vitamin E (0.3 mg + 22.5 mg/kg b.w., respectively) 14 days prior to exposure to the higher dose (4.78 mg/kg) of FIP for another 14 days. Fipronil exposure at medium and high doses showed lowered values of red blood cell count (RBC), hematocrit (HCT), hemoglobin (HGB), white blood cell (WBC), and platelet (PLT) counts after 28-day exposure, compared to the control. All three doses caused significant increases in levels of liver-function biomarkers, i.e., aspartate amino transaminase (AST), alanine amino transaminase (ALT), alkaline phosphatase (ALP), cholesterol, and bilirubin levels compared to the control. Levels of biomarkers related to kidney functions, i.e., urea, uric acid, and creatinine, increased significantly than these of the control. Likewise, the oxidative stress indices, i.e., hydrogen peroxide (H2O2) and malondialdehyde (MDA), significantly increased at the higher and medium doses, while antioxidant enzymes, catalase (CAT) and superoxide dismutase (SOD), decreased significantly. On the other hand, prior administration of selenium + vitamin E in the FIP-exposed mice led to restore values of most hematological parameters nearly to these of the control. Also, the levels of AST, total protein, and creatinine seemed to be restored to the control values. Interestingly, pretreatment with selenium + vitamin E restored the levels of antioxidant enzymes, CAT and SOD, to the control values, whereas, oxidative stress indices, H2O2 and MDA, remained significantly high. It is our thought that the sublethal dose less than 1.43 mg/kg b.w. of commercial formulation of FIP (COACH® 200 SC) could be considered as no-observed-adverse-effect-level(NOAEL) under our present experimental conditions at short-term toxicity study. On the other hand, the higher sublethal doses, 4.78 and 2.87 mg/kg b.w., induced significant adverse effects in biomarkers and may be deleterious to human health following long-term exposure.

Histological effect of Curcuma longa and Zingiber officinale on the liver damage after treatment with hydrogen peroxide in Rats (Rattus norvegicus)

This research is aimed at investigating the hepatotoxic effect of hydrogen peroxide and effects of Curcuma longa and zingiber officinale on this hepatotoxicity. In present study we administration hydrogen peroxide to animals rat for induced high cholesterol in blood and caused liver damage . These were carried out via estimation of liver function tests and histochange in the liver. Fourteen adult Westar rats Rattus norvegicus were used for the experimental investigations. They were grouped into four groups:. Animals in group one served as the control group. Group two consists of rats administered with hydrogen peroxide (1% body weight) .Group three consists of rats administered with hydrogen peroxide and Curcuma longa (200 mg/ kg body weight).Group four administered with hydrogen peroxide and zingiber officinale(200 mg/ kg body weight). All animals administration orally, the experimental period lasted for 30 days. The rats were sacrificed on the thirteen day. The blood samples collected by cardiac puncture and placed in appropriately labeled bottles for the various assays. And section of liver isolated. There was a decrease in the aspartate aminotransaminase level, alanine aminotransferase level are significantly lower (P<0.05) in the rats of the control group than both the rats treated with hydrogen peroxide only and the ones treated peroxide with Curcuma longa and peroxide with zingiber officinale These were lower in the rats treated with Curcuma longa and zingiber officinale than the rats treated with hydrogen peroxide alone. These reduction is however not statistically significant and it presents that these could be dosage related. The histological change in the section of liver showed as clusters of inflammatory cells surrounding portal area or within the parenchyma was seen. Vacuation within hepatocytes and congestion in centeral vien were observed and was generally necrosis hepatocytes compare compared with animals treatment in extracts a decreasing in degenerative changes was noticed in proxide + curcuma extract, there was a moderate decreasing of hepatocellular damage and portal tract fibrosis, inflammatory infiltration compared to peroxide group .But in the fourth group zingiber +hydrogen peroxide no hepatocellular damage,. It was noticed that this group has the same histological appearance as the control group. These results indicate that hydrogen peroxide is induce to increase the cholestrole and caused hepatotoxic but that Curcuma longa and zingiber officinale may be a protective effect on this hepatotoxicity.

Clinical features of acute human immunodeficiency virus infection in Taiwan: A multicenter study.

Acute HIV infection is characterized by a high concentration of HIV RNA in the plasma and rapid depletion of the CD4 cell count. This multicenter, retrospective observational study aimed to characterize the manifestations of acuteHIV infection in Taiwan. Between 1 January 2012 and 31 December 2016, all patients aged 20 years or greater who presented with acute HIV infection were included. Demographic and clinical characteristics of the patients at diagnosis were collected. Baseline laboratory assessment included hemogram, CD4 count, plasma HIV RNA load (PVL), serologic markers of syphilis and hepatitis A, B, and C viruses, and serum biochemistry. The proportion of acute HIV infection was 6.9% among the patients with newly diagnosed HIV infection during the study period. The most common presenting symptoms of acute HIV infection were fever, fatigue, and myalgia. The median PVL at diagnosis was 5.9 log10copies/ml, and median CD4 count was 307cells/mm3. A total of 68 patients (27%) had baseline CD4 count less than 200cells/mm3. Multiple logistic regression analysis, showed that the baseline CD4 count (OR, 4.02; p=0.013) and aspartate aminotransaminase levels (OR, 3.49; p=0.002) were associated with high PVL (>5 log10copies/ml); and high baseline PVL (OR, 2.64; p=0.002) was associated with symptomatic acute HIV infection. Manifestations of acute HIV infection are nonspecific and of wide spectrum ranging from fever to severe illness. A higher proportion of patients with initial CD4 counts of 200cells/mm3 or less during acute HIV infection warrants early, timely diagnosis and treatment to prevent rapid disease progression.

Paracetamol and Hydrogen peroxide-induced tissue alterations are reduced by Costus afer extract

Aim/Objective: To evaluate the effect of the methanolic extract of Costus afer stem on paracetamol-induced tissue injury in rats (in-vivo) and its ability to reduce hydrogen peroxide-induced erythrocyte damage (in-vitro). Methods: Twenty-five rats were acclimatized for two weeks and randomized into five groups. Group I were untreated controls, while each rat in groups III - V was given a single intraperitoneal-administration of paracetamol (800 mg/kg b.w.). Prior to the administration of paracetamol, rats in groups II and IV were orally given Costus afer extract at 200 mg/kg b.w while rats in group V were given 400 mg/kg b.w. extract once daily for four days. In the other experiment, hydrogen peroxide was used to induce erythrocyte damage (after isolating erythrocytes from whole blood) and subsequently incubated with the extract at different concentrations. Markers for tissue and erythrocyte damage were assessed in serum, tissue homogenates and erythrocytes. Results: Paracetamol caused marked elevations (p < 0.05) in the levels of alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), alkaline phosphatase (ALP), urea and creatinine in serum. The levels of thiobarbituric acid reactive species (TBARS) in both liver and kidney were also raised over control (p < 0.05) while the activities of superoxide dismutase (SOD) and catalase were reduced over untreated controls (p < 0.05). Pre-treatment of rats with Costus afer extract (p.o.) caused significant reduction in serum levels of ALT, AST, ALP, urea, creatinine and tissue TBARS closer to control values (p < 0.05). Pre-treatment of the rats with the plant extract also increased the activities of SOD and catalase in both liver and kidney. Apart from the levels of TBARS in liver and catalase in kidney, rats pre-treated with 400 mg/kg b.w. extract showed greater response than pre-treatment with 200 mg/kg b.w. The extract also reduced hydrogen peroxide-induced erythrocyte damage assessed as haemolysis and lipid peroxidation which was concentration-dependent (p < 0.05). Conclusion: This indicated that Costus afer possesses the ability to protect the various tissues against chemical-induced injury.

ATTENUATION OF CARBON TETRACHLORIDE AND ETHANOL-INDUCED HEPATIC FIBROSIS IN RATS BY CALLIGONUM COMOSUM SHOOT EXTRACT

ABSTRACTObjective: This study was designed to evaluate the hepatoprotective and antioxidant effects of methanolic extract of Calligonum comosum (C. comosum)shoots on the hepatic fibrosis induced by carbon tetrachloride and ethanol (CCl4/ethanol) in rats.Methods: A liver fibrosis was induced in Sprague Dawley rats by oral administration of CCl4 (1 ml/kg body weight, twice weekly for 10 weeks) alongwith ethanol (10% in drinking water 1 week before CCl4 administration and throughout the experiment). Rats were pretreated with C. comosumextract (daily, orally at a dose of 50 mg/kg body weight 1 week before CCl4 administration). At the end of the experiment, serum, and liver sampleswere subjected to biochemical investigations. In addition, liver and kidney tissues were evaluated for histopathological changes.Results: C. comosum extract pretreatment significantly reduced CCl4 - induced elevation in serum levels of aspartate aminotransaminase, alanineaminotransaminase, alkaline phosphatase, total bilirubin, urea, creatinine, and significantly elevated serum contents of total protein and albumin, aswell as an improvement in hepatic protein content, albumin/globulin ratio, body weight and relative liver and kidney weights. C. comosum extract alsosignificantly increased the hepatic levels of glucose-6-phosphatase, glutathione peroxidase, glutathione-S-transferase, catalase, superoxide dismutase,and glutathione with significant decrease in the contents of malondialdehyde and protein carbonyl. In addition, downregulation in expression ofthe fibrotic marker matrix metalloproteinase-2 was observed. C. comosum extract also ameliorated histopathological changes of CCl4/ethanol groupwhich further evidenced the biochemical findings.Conclusion: Our results confirmed that the methanolic extract of C. comosum shoots effectively protect against CCl4/ethanol-induced liver fibrosis,through its antioxidant property.Keywords: Calligonum comosum, Hepatic fibrosis, Carbon tetrachloride, Hepatoprotective effect, Antioxidants, Matrix metalloproteinase-2.

Longitudinal Analysis of Patient Specific Predictors for Mortality in Sickle Cell Disease.

IntroductionWhite Blood Cell (WBC) count, %HbF, and serum creatinine (Cr), have been identified as markers for increased mortality in sickle cell anemia (SCA) but no studies have examined the significance of longitudinal rate of change in these or other biomarkers for SCA individuals.MethodsClinical, demographic and laboratory data from SCA patients seen in 2002 by our hospital system were obtained. Those who were still followed in 2012 (survival cohort) were compared to those who had died in the interim (mortality cohort). Patients lost to follow-up were excluded. Age adjusted multivariable Cox proportional hazards models were constructed to assess hazard ratios of mortality risk associated with the direction and degree of change for each variable.Results359 SCA patients were identified. Baseline higher levels of WBC, serum creatinine and hospital admissions were associated with increased mortality, as were alkaline phosphatase and aspartate aminotransaminase levels. Lower baseline levels of %HbF were also associated with increased mortality. When longitudinal rates of change for individuals were assessed, increases in Hb or WBC over patient baseline values were associated with greater mortality risk (HR 1.54, p = 0.02 and HR 1.16, p = 0.01 with negative predictive values of 87.8 and 94.4 respectively), while increasing ED use was associated with decreased mortality (HR 0.84, p = 0.01). We did not detect any increased mortality risk for longitudinal changes in annual clinic visits or admissions, creatinine or %HbF.ConclusionsAlthough initial steady state observations can help predict survival in SCA, the longitudinal course of a patient may give additional prognostic information.

Prognostic Factors of the Efficacy of High-dose Corticosteroid Therapy in Hemolysis, Elevated Liver Enzymes, and Low Platelet Count Syndrome During Pregnancy: A Meta-analysis.

The aim of this study was to identify the factors which can affect the efficacy of corticosteroid (CORT) therapy in the management of hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome.Research articles reporting the efficacy of CORT therapy to HELLP syndrome patients were searched in several electronic databases including EMBASE, Google Scholar, Ovid SP, PubMed, and Web of Science. Study selection was based on predefined eligibility criteria. Efficacy was defined by the changes from baseline in HELLP syndrome indicators after CORT therapy. Meta-analyses were carried out with Stata software.Data of 778 CORT-treated HELLP syndrome patients recruited in 22 studies were used in the analyses. Corticosteroid treatment to HELLP syndrome patients was associated with significant changes from baseline in platelet count; serum levels of aspartate aminotransaminase, alanine transaminase, and lactic dehydrogenase (LDH); mean blood pressure; and urinary output. Lower baseline platelet count predicted higher change in platelet count after CORT therapy. Lower baseline platelet count and lower baseline urinary output predicted greater changes in LDH levels after CORT therapy. There was also an inverse relationship between the change from baseline in LDH levels and intensive care duration. Higher CORT doses were associated with greater declines in the aspartate aminotransaminase, alanine transaminase, and LDH levels. Incidence of cesarean delivery was inversely associated with the gestation age. The percentage of nulliparous women had a positive association with the intensive care stay duration.High-dose CORT therapy to HELLP syndrome patients provides benefits in improving disease markers and reducing intensive care duration, especially in cases such as mothers with much lower baseline platelet count and LDH levels.

Protective Effect of Hericium erinaceus on Alcohol Induced Hepatotoxicity in Mice.

We investigated the effects of Hericium erinaceus (HEM) on liver injury induced by acute alcohol administration in mice. Mice received ethanol (5 g/kg BW) by gavage every 12 hrs for a total of 3 doses. HEM (200 mg/kg BW) was gavage before ethanol administration. Subsequent serum alanine aminotransferase (ALT) level, aspartate aminotransaminase (AST) level, Maleic dialdehyde (MDA) level, hepatic total antioxidant status (TAOS), and activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were determined by ELISA and immunohistochemistry, respectively. HEM administration markedly (P < 0.05) decreased serum ALT, AST, and MDA levels. The hepatic histopathological observations showed that HEM had a relatively significant role in mice model, which had alcoholic liver damage. In conclusion, we observed that HEM (200 mg/kg BW) supplementation could restrain the hepatic damage caused by acute alcohol exposure.

Effect of co-administration of Angelicae gigantis radix and Lithospermi radix on rat hepatic injury induced by carbon tetrachloride.

Background:Co-administration of Angelicae gigantis radix (AGR) and Lithospermi radix (LR) has been commonly applied to patients to treat cardiac and hepatic disorders. Individual bioactivities of these herbal medicines have been widely investigated, but the hepatoprotective effects of co-treatment of AGR and LR have yet to be clarified.Objective:The present study investigated the protective effects of extracts of AGR and LR on carbon tetrachloride (CCl4) induced hepatic injury.Materials and Methods:In this study, we measured the hepatoprotective activity of individual and co-treatment of the two herbal medicines on hepatic injury induced by CCl4 by measuring different biochemical parameters such as serum aspartate aminotransaminase (AST) and serum alanine aminotransaminase (ALT). Microarray technology also used to compare ontological difference with individual and co-treatment of these two.Results:Combined treatment with AGR and LR (AGR + LR) decreased AST and ALT level in serum which demonstrate hepatoprotective effect of the therapy. When the effect of AGR and LR according to treatment conditions was measured, co-treatment showed the most prominent effect on hepatic injury by CCl4 rather than individual treatment condition. We further defined gene set that could be the molecular target of herbal effect on hepatic injury by CCl4 using bioinformatical analysis of interaction network. Highly recovered genes by treating AGR + LR play significant roles in response to hepatic injury induced by CCl4.Conclusion:Combined treatment with AGR and LR showed synergistic protective effects on the CCl4-induced rat hepatic tissue injury.