Blood Levels Of Aspartate Aminotransferase Research Articles

An open-label, controlled trial of the clinical effects of Laennec® in patients with nonalcoholic steatohepatitis or cirrhosis

Objective: to evaluate the efficacy and safety of human placenta hydrolysate (HPH) Laennec® in the treatment of nonalcoholic fatty liver disease (NAFLD) in a clinical trial.Material and methods. The study involved hospitalized NAFLD patients (with non-alcoholic steatohepatitis, cirrhosis) (n=34, mean age 53±14 years). In the therapy group (n=17), patients received Laennec® HPH (4 ml intravenous drip infusion in a solution of 5% glucose 5 times a week for 2 weeks). In the control group (n=17), patients hospitalized in other departments of the clinic did not receive any therapy for NAFLD. The effectiveness of therapy was assessed after 2 and 3 weeks by subjective NAFLD symptoms (fatigue, anorexia, bloating, constipation, nausea, and pain in hypochondrium) and biochemical indicators of liver function: levels of blood serum aspartate aminotrans-ferase (AST), alanine notransferase (ALT), gamma-glutamyltransferase (GGT).Results. At the start of the study, there were no significant differences between the groups in the values of the studied indicators of liver function: blood levels of AST, ALT, GGT, etc. By the end of Week 1, a significant decrease in AST levels was registered in the group receiving Laennec® (–35 U/l; control: –8 U/l; p<0.001), ALT (–45 U/l; control: –10 U/l; p<0.001), and GGT (–23 U/l; control: –8 U/l; p=0.084; trend). At the end of the study (Week 3), the decrease in AST, ALT and GGT levels towards the normal range was even more pronounced for all three biomarkers: AST (–62 U/l; control: –23 U/l; p<0.001), ALT (–78 U/l; control: –20 U/l; p<0.001), GGT (–40 U/l; control: –15 U/l; p=0.005). Subjective NAFLD symptoms significantly improved after 3 weeks. No adverse effects were identified with the use of HPH. Conclusion. Laennec® is an effective and safe treatment for NAFLD.

A serial analysis of serum aspartate aminotransferase levels in patients with acute encephalopathy with biphasic seizures and late reduced diffusion and prolonged febrile seizure

BackgroundThere are no established biomarkers for diagnosing acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) in the early acute phase, called “the 1st seizure phase”. Based on our clinical experience, we hypothesized that serial examinations of blood levels of aspartate aminotransferase (AST) in children with febrile convulsive status epilepticus (FCSE) revealed higher levels in patients with AESD in the 1st seizure phase than in those with prolonged febrile seizures (PFs). MethodsTo test our presented hypothesis, we retrospectively investigated changes in serum AST in patients with FCSE due to AESD (n = 11) or PFs (n = 27) who were serially examined within 48 h of the onset of convulsions. ResultsThe rate of increase in AST was significantly higher in patients with AESD than in those with PFs. The rate of increase in AST correlated with previously reported scoring systems, i.e., Yokochi and Tottori scores, for the prediction of AESD. A positive correlation between the rate of increase in AST and creatinine levels in the first examination were observed; however, creatinine levels did not significantly differ between the AESD and PFs groups in the first or second examination. Blood levels of pH, ammonia, and sugar in the first examination and C-reactive protein in the second examination were significantly higher in the AESD group than in the PFs group. ConclusionsThe present study revealed that the rate of increase in AST was significantly higher in patients with AESD than in those with PFs. A novel predictive scoring system needs to be established in combination with the rate of increase in AST and reported clinical parameters, which will improve the prognosis of patients with FCSE.

Effects of Dietary Supplementation of Oregano Bioactive Lipid Compounds and Silver Nanoparticles on Broiler Production

Feed additives could be added in the diets of broiler chickens to improve performance and for sustainable broiler production. The objective of this study was to evaluate the effectiveness of feeding broiler chickens with oregano bioactive lipid compounds (OBLC) and silver nanoparticles (Nano-Silver) on growth, viability, economics, carcass criteria, silver retentions, and serum biochemistry. One-day-old, unsexed Ross 308 broiler chicks (n = 320) were divided into four treatment groups. Ten replicates of eight birds each for each treatment were used. Treatments were: CONT (control diet), OBLC (CONT diet supplemented with 150 mg/kg OBLC), Nano-Silver (CONT diet supplemented with 4 mg/kg Nano-Silver), and CONT diet supplemented with OBLC + Nano-Silver at levels mentioned above were used for the study. The experiment lasted for 35 days. Supplementing OBLC and Nano-Silver individually or in combination improved (p < 0.01) body weight and feed conversion ratio when compared to CONT. The supplemented groups had a lower death rate than the CONT group, resulting in a higher net return. Supplementing broiler birds with OBLC, Nano-Silver, or their combination boosted dressing percentage and decreased abdominal fat when compared to CONT. Blood levels of aspartate aminotransferase, alanine transaminase, creatinine, and urea were lowered in broilers fed OBLC, Nano-Silver, or combination diets. Overall, the current study demonstrates that broiler chickens fed diets with OBLC and Nano-Silver, either alone or in combination, improved growth performance, liver functions, dressing percent, silver absorption and decreased abdominal fat. The best performance was observed in the combination of OBLC and Nano-Silver group compared to other treatments.

Systematic Review and Meta-Analysis of the Usefulness of Epicardial Fat Thickness as a Non-Invasive Marker of the Presence and Severity of Nonalcoholic Fatty Liver Disease.

We performed a systematic review and meta-analysis to assess the association between epicardial fat thickness (EFT) and nonalcoholic fatty liver disease (NAFLD). This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) and was based on a registered protocol (CRD 4201809 5493). We searched Medline and Embase until December 2021 for studies reporting on the association between EFT and NAFLD. Qualitative reviews, meta-analyses and meta-regressions were performed to explore this association. Effect sizes are reported as standardized mean differences. We included 12 studies, comprising 3610 individuals. EFT was evaluated with trans-thoracic echocardiography in nine studies, two studies using cardiac computed tomography and one study using magnetic resonance imaging (MRI). The presence of NAFLD was evaluated using transabdominal liver ultrasound in nine studies. Other studies used histology, magnetic resonance spectroscopy and MRI-derived proton density fat fraction. Liver biopsy was performed to assess the severity of NAFLD in four studies. The random-effects meta-analysis indicated that, as compared to control patients with lean livers, patients with NAFLD displayed significantly higher EFT (standardized mean difference 0.61, 95% confidence interval: 0.47–0.75, p < 0.0001, I2 = 72%). EFT was further significantly higher in patients with severe liver steatosis versus patients with mild–moderate liver steatosis (standardized mean difference 1.21 95% confidence interval: 0.26–2.16, p < 0.001, I2 S = 96%). Through the meta-regression analysis, we found that patients with increasingly higher blood levels of aspartate aminotransferase displayed an increasingly higher depth of association. The current meta-analysis suggests that EFT may represent a useful surrogate for assessing the presence and severity of NAFLD in a non-invasive manner.

Fatty acids composition and in vivo biochemical effects of Aleurites moluccana seed (Candlenut) in obese wistar rats

BackgroundCandlenut (CN) has been used indiscriminately for weight loss. In vivo effects of CN in different doses are scarce.ObjectiveTo evaluate the effects of CN ingestion in obese rats.DesignThirty animals (obese and non-obese) received one of three different types of treatments: placebo, CN ingestion in a popular therapeutic regimen (8 days with oral administration of 0.2 mg/kg followed by 20 days with doses of 0.4 mg/kg), and ingestion of a doubled popular dose—called 2CN. Treatment was maintained for 28 days.ResultsThe fatty acid profile of CN indicated mainly linolelaidic and palmitoleic acids. Rats receiving CN and 2CN showed reduced plasmatic levels of glucose and lipoproteins (p < 0.05). A dose-dependent carcass fat reduction was observed (p < 0.05). Blood levels of aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT) reduced with CN and increased with 2CN doses (p < 0.05). Alanine aminotransferase (ALT) and the atherogenic index remained similar among all treatments (p > 0.05). Hepatic vacuolation decreased with CN, but the 2CN dose produced mononuclear leucocyte infiltrate.ConclusionsAlthough CN presented beneficial effects on the metabolism of rats, it also caused increased risk of liver damage.

Replacing concentrates with a high-quality hay in the starter feed of dairy calves: II. Effects on the development of chewing and gut fermentation, and selected systemic health variables

Early development of the rumen, rumination, and fermentation is highly important in dairy calves. Yet, common rearing practices with feeding of concentrate-rich starters may jeopardize them because of lacking physically effective fiber (peNDF). The main objective of this study was to establish the influence of the composition of the calf starter feed (only forage with 2 different qualities or concentrate-rich starter diet) on chewing behavior, rumen development, rumen and hindgut fermentation, and selected systemic health and stress variables of dairy calves. The experiment was carried out with 40 newborn Holstein-Friesian calves, randomly assigned to 4 different solid feed treatments: MQH = 100% medium-quality hay (9.4 MJ metabolizable energy, 149 g of crude protein, and 522 g of neutral detergent fiber/kg of dry matter); HQH = 100% high-quality hay (11.2 MJ of metabolizable energy, 210 g of crude protein, 455 g of neutral detergent fiber/kg of dry matter); MQH+C = 30% MQH + 70% starter concentrate; HQH+C = 30% HQH + 70% starter concentrate). All calves were up to 14 wk in the trial and received acidified whole milk ad libitum in the first 4 wk of life, thereafter in reduced quantity until weaning on 12 wk of age. Water and the solid feed treatments were available ad libitum throughout the trial. Chewing activity was measured in wk 4, 6, 10, and 12 using RumiWatch halters. Until wk 3, rumen fluid, feces and blood were sampled weekly, thereafter every 2 wk. Rumen mucosal thickness (RMT) was measured on the same days with rumen fluid samples. Data showed that calves fed the HQH diet consumed more peNDF and this was associated with longer rumination time (591 min/d) and more ruminating boli (709 boli/d) than calves fed concentrate-rich diets (MQH+C: 430 min/d, 518 boli/d; HQH+C: 430 min/d, 541 boli/d), whereas the MQH group was intermediate (539 min/d, 644 boli/d). Ruminal and fecal pH were higher in calves fed only hay (especially MQH) compared with calves with concentrate supplementation. In both hay-fed groups, ruminal and fecal short-chain fatty acids were shifted toward acetate, whereas only the HQH diet increased the butyrate proportion in the ruminal short-chain fatty acids profile. Ruminal ammonia concentration was at a high level only in the first 3 wk and decreased thereafter. Feeding HQH tended to increase ruminal ammonia, likely because of its high crude protein content and ruminal degradability as well as lower assimilation from rumen microbes. The RMT similarly, though nonlinearly, increased in all groups over the course of the experiment. When using RMT as an indicator of rumen development in dairy calves in the practice, our data suggest an RMT of 1.7mm and >2mm at wk 5 and 10 of life, respectively. Feeding did not affect the blood levels of aspartate aminotransferase, gamma glutamyl transferase, glutamate dehydrogenase, and cortisol. In conclusion, feeding high-quality hay, instead of concentrate-rich starter feeds, resulted in improved rumination and ruminal fermentation profile, without affecting ruminal pH and systemic and stress health variables.

Protective Activity of Beetroot Extract on Doxorubicin-Induced Hepatic and Renal Toxicity in Rat Model

BACKGROUND: The administration of doxorubicin can increase the production of reactive oxygen species (ROS) and disrupt the balance of antioxidant defenses triggered a cell damage including liver cells and renal cells. Antioxidant from medicinal plants have play role in protecting the cells against ROS. Beetroot tuber contains various phytochemical compound that has an antioxidant property. AIM: The purpose of the study was to determine the protective effect of beetroot ethanol extract on concurrent use of doxorubicin for 15 days by measuring blood levels of aspartate aminotransferase, alanine aminotransferase, Creatinine, blood urea nitrogen and histopathological changes. MATERIALS AND METHODS: Twenty-five male white rats as weighing 180–200 g were divided into five treatment groups. Group I was the normal control group, Group II was a negative control group that only injected doxorubicin with a cumulative dose of 15 mg/kg body weight (BW) for 15 days. Group III-V was the test group given beetroot extract (BE) at doses of 100, 200 and 400 mg, respectively, for 15 days with doxorubicin. RESULTS: The group treated with BE at a dose of 200 mg/kg BW could improve serum levels of liver enzymes compared with negative controls (p &lt; 0.05). The group treated with BE at a dose of 100 mg/kg BW also showed an improved effect on creatinine and BUN levels of rats compared to negative controls (p &lt; 0.05). All parameters showed that the protective activity of beetroot ethanol extract was dependent on increasing the dose. CONCLUSION: This research proves that the compound contained in beetroot ethanol extract has protective activity in liver and kidney of rats induced by doxorubicin.

Low-Level Saturated Fatty Acid Palmitate Benefits Liver Cells by Boosting Mitochondrial Metabolism via CDK1-SIRT3-CPT2 Cascade.

Saturated fatty acids (SFAs) (the "bad" fat), especially palmitate (PA), in the human diet are blamed for potential health risks such as obesity and cancer because of SFA-induced lipotoxicity. However, epidemiological results demonstrate a latent benefit of SFAs, and it remains elusive whether a certain low level of SFAs is physiologically essential for maintaining cell metabolic hemostasis. Here, we demonstrate that although high-level PA (HPA) indeed induces lipotoxic effects in liver cells, low-level PA (LPA) increases mitochondrial functions and alleviates the injuries induced by HPA or hepatoxic agent carbon tetrachloride (CCl4). LPA treatment in mice enhanced liver mitochondrial activity and reduced CCl4 hepatotoxicity with improved blood levels of aspartate aminotransferase (AST), alanine transaminase (ALT), and mitochondrial aspartate transaminase (m-AST). LPA-mediated mitochondrial homeostasis is regulated by CDK1-mediated SIRT3 phosphorylation, which in turn deacetylates and dimerizes CPT2 to enhance fatty acid oxidation. Thus, an advantageous effect is suggested by the consumption of LPA that augments mitochondrial metabolic homeostasis via CDK1-SIRT3-CPT2 cascade.

Antihypertensive efficacy and safety of Vaccinium arctostaphylos berry extract in overweight/obese hypertensive patients: A randomized, double-blind and placebo-controlled clinical trial

ObjectivesTo evaluate the antihypertensive efficacy and safety of a standardized Vaccinium arctostaphylos (V. arctostaphylos) berry hydro-alcoholic extract in the overweight/obese hypertensive patients. DesignRandomized placebo-controlled trial. SettingBaqiyatallah hospital (Tehran, Iran). InterventionsThe antihypertensive efficacy and safety of 3-month intake of 400 mg extract capsule three times daily alongside standardized anti-hypertensive regimen in the treatment of 50 patients was compared with the placebo (n = 50). Main outcome measuresSBP (systolic blood pressure), DBP (diastolic blood pressure), body mass index, waist circumference, CBC (complete blood count), blood levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase), ALP (alkaline phosphatase), BUN (blood urea nitrogen) and creatinine. ResultsSBP decreased from 152.1 ± 7.7 to 140.5 ± 10.7 in the V. arctostaphylos group and from 152.9 ± 8.1 to 150.8 ± 9.3 in the placebo group (P < 0.001). DBP decreased from 90.3±8 to 82.1±8.8 in the V. arctostaphylos group and from 89.6 ± 7.8 to 87.6 ± 7.9 in the placebo group (P < 0.001).The extract capsule had no significant effect on the other parameters (P > 0.05). Moreover, no drug side effect and adverse interaction with other antihypertensive drugs was observed in the patients. ConclusionsV. arctostaphylosberry extract improves blood pressure control and has safety and tolerability in the overweight/obese hypertensive patients taking standard antihypertensive drugs.

Steatosis caused by experimental periodontitis is reversible after removal of ligature in rats.

Periodontitis may promote harmful systemic effects such as changes in hepatic tissues. The purpose of this study was to investigate whether the steatosis and oxidative stress caused by experimental periodontitis are reversible in the liver. Twenty-four rats were divided into three groups: control, periodontitis and P20-20 (20days with experimental periodontitis and 20days without experimental periodontitis, to verify the reversibility of hepatic injuries). The following parameters were assessed: gingival bleeding index, probing pocket depth, myeloperoxidase activity, alveolar bone loss for periodontal tissues; liver weights, histopathological scores for steatosis, inflammation and necrosis in liver; glutathione, malondialdehyde, total cholesterol and triglyceride concentrations in hepatic tissues; and blood levels of aspartate aminotransferase, alanine aminotransferase, albumin, gamma-glutaryl transferase, total cholesterol and random glucose. Gingival bleeding index, probing pocket depth, myeloperoxidase and alveolar bone loss parameters demonstrated the development of periodontitis. There was a significant reduction in the steatosis score of animals from the P20-20 group when compared with the periodontitis group. P20-20 group presented significantly higher glutathione (11 times) and lower malondialdehyde (nearly 23%), total cholesterol (both in blood and hepatic tissue) and triglyceride concentrations compared with the periodontitis group. For levels of aspartate aminotransferase, alanine aminotransferase, albumin, gamma-glutaryl transferase and random glucose, a significant difference between the groups was not observed. Our results demonstrate that the microvesicular steatosis caused by periodontitis in rats is reversible after removal of the ligature, which is associated with the increase in oxidative stress and lipid peroxidation in the liver.

Chenopodium ambrosioides L. extract prevents bone loss.

To evaluate the effect of the Chenopodium ambrosioides L (mastruz) extract for preventing bone loss and bone metabolism in ovariectomized rats. Twelve rats were subjected to bilateral ovariectomy for inducing osteoporosis. After surgery, they were divided into two groups: Ovariectomy-control group (G1, n=6), receiving 0.5 ml distilled water by gavage for 30 days, and Ovariectomy plus mastruz group (G2, n=6), receiving 0.5 ml of the hydroalcoholic extract of mastruz at 10% concentration (50mg) daily, for the same period. Then, the blood of the animals was collected for further biochemical analysis (liver function) and tibia and liver were removed for histological and histomorphometric analyses. The cortical bone was significantly larger in the G2 than G1, whereas G1 presented the highest amount of adipocytes in the bone marrow (p<0.05). The blood levels of aspartate aminotransferase, triglycerides and cholesterol were significantly higher, whereas globulin and lactate dehydrogenase were smaller in G2 than G1. The hydroalcoholic extract of mastruz has effects on bone metabolism by changing blood proteins and enzymes and preventing both bone loss and the substitution of bone marrow cells by.

Gangrenous cholecystitis: mortality and risk factors.

As a serious complication of cholelithiasis, gangrenous cholecystitis presents greater mortality than noncomplicated cholecystitis. The aim of this study was to specify the risk factors on mortality. 107 consecutive patients who underwent surgery due to gangrenous cholecystitis between January 1997 and October 2011 were investigated retrospectively. The study included 60 (56.1%) females and 47 (43.9%) males, with a mean age of 60.7 ± 16.4 (21-88) years. Cardiovascular diseases were the most frequently accompanying medical issues (24.3%). Thirty-six complications (33.6%) developed in 29 patients, and surgical site infection was proven as the most common. Longer delay time prior to hospital admission, low white blood cell count, presence of diabetes mellitus, higher blood levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and total bilirubin, pericholecystic fluid in abdominal ultrasonography, and conversion from laparoscopic surgery to open surgery were identified as risk factors affecting mortality (P < 0.001, P = 0.001, P = 0.044, P = 0.005, P = 0.049, P = 0.009, P = 0.022, P = 0.011, and P = 0.004, respectively). Longer delay time prior to hospital admission and low white blood cell count were determined as independent risk factors affecting mortality.

Protection against Klebsiella pneumoniae using lithium chloride in an intragastric infection model.

Intragastric Klebsiella pneumoniae infections of mice can cause liver abscesses, necrosis of liver tissues, and bacteremia. Lithium chloride, a widely prescribed drug for bipolar mood disorder, has been reported to possess anti-inflammatory properties. Using an intragastric infection model, the effects of LiCl on K. pneumoniae infections were examined. Providing mice with drinking water containing LiCl immediately after infection protected them from K. pneumoniae-induced death and liver injuries, such as necrosis of liver tissues, as well as increasing blood levels of aspartate aminotransferase and alanine aminotransferase, in a dose-dependent manner. LiCl administered as late as 24 h postinfection still provided protection. Monitoring of the LiCl concentrations in the sera of K. pneumoniae-infected mice showed that approximately 0.33 mM LiCl was the most effective dose for protecting mice against infections, which is lower than the clinically toxic dose of LiCl. Surveys of bacterial counts and cytokine expression levels in LiCl-treated mice revealed that both were effectively inhibited in blood and liver tissues. Using in vitro assays, we found that LiCl (5 μM to 1 mM) did not directly interfere with the growth of K. pneumoniae but made K. pneumoniae cells lose the mucoid phenotype and become more susceptible to macrophage killing. Furthermore, low doses of LiCl also partially enhanced the bactericidal activity of macrophages. Taken together, these data suggest that LiCl is an alternative therapeutic agent for K. pneumoniae-induced liver infections.

Experimental Phage Therapy in Treating Klebsiella pneumoniae -Mediated Liver Abscesses and Bacteremia in Mice

Intragastric inoculation of mice with Klebsiella pneumoniae can cause liver abscesses, necrosis of liver tissues, and bacteremia. A newly isolated phage (φNK5) with lytic activity for K. pneumoniae was used to treat K. pneumoniae infection in an intragastric model. Both intraperitoneal and intragastric administration of a single dose of φNK5 lower than 2 × 10(8) PFU at 30 min after K. pneumoniae infection was able to protect mice from death in a dose-dependent manner, but the efficacy achieved with a low dose of φNK5 by intragastric treatment provided the more significant protection. Phage φNK5 administered as late as 24 h after K. pneumoniae inoculation was still protective, while intraperitoneal treatment with phage was more efficient than intragastric treatment as a result of the dissemination of bacteria into the circulation at 24 h postinfection. Surveys of bacterial counts for mice treated with φNK5 by the intraperitoneal route revealed that the bacteria were eliminated effectively from both blood and liver tissue. K. pneumoniae-induced liver injury, such as liver necrosis, as well as blood levels of aspartate aminotransferase and alanine aminotransferase and inflammatory cytokine production, was significantly inhibited by φNK5 treatment. These data suggest that a low dose of φNK5 is a potential therapeutic agent for K. pneumoniae-induced liver infection.

Curcumin protects rats against acetaminophen-induced hepatorenal damages and shows synergistic activity with N-acetyl cysteine

Acetaminophen is one of the most popular analgesic and antipyretic drugs and its overdose, which can cause severe damage to liver and kidneys, is one of the most common reasons of emergency admissions. In this study we investigated the effects of curcumin, derived from plant Curcuma longa, on acetaminophen toxicity, and the possibility of combining therapy of curcumin and N-acetyl cysteine (NAC) to treat this toxicity. The experiments were conducted on 72 male Sprague–Dawley rats randomly divided into 12 groups. Control group was left without treatment, and the other groups were treated with different combinations of acetaminophen, curcumin and NAC. 15 min after intraperitoneal injection, the blood level of curcumin was measured using HPLC. Blood levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase), blood urea nitrogen and creatinine were determined 18 and 42 h after acetaminophen injection. One week later, the left kidney and the caudate lobe of the liver were harvested to assay glutathione peroxidase, catalase and malondialdehyde. The right kidney and the remaining lobes of the liver were used for histopathology. Analysis of organ function and oxidation parameters showed that curcumin significantly reduced toxic effects of acetaminophen on the liver and kidneys in a dose-dependent manner and significantly potentiated the protective effects of NAC. These findings were confirmed by histopathology. It is concluded that curcumin can protect the liver and kidney from the damage caused by acetaminophen overdose. Moreover, curcumin has the potential to be used in a combination therapy with NAC, significantly decreasing the therapeutic dose of NAC and therefore its side-effects.

Pharmacological Inhibition of Transforming Growth Factor β Signaling Decreases Infection and Prevents Heart Damage in Acute Chagas' Disease

Chagas' disease induced by Trypanosoma cruzi infection is an important cause of mortality and morbidity affecting the cardiovascular system for which presently available therapies are largely inadequate. We previously reported that transforming growth factor beta (TGF-beta) is implicated in several regulatory aspects of T. cruzi invasion and growth and in host tissue fibrosis. This prompted us to evaluate the therapeutic action of an inhibitor of TGF-beta signaling (SB-431542) administered during the acute phase of experimental Chagas' disease. Male Swiss mice were infected intraperitoneally with 10(4) trypomastigotes of T. cruzi (Y strain) and evaluated clinically for the following 30 days. SB-431542 treatment significantly reduced mortality and decreased parasitemia. Electrocardiography showed that SB-431542 treatment was effective in protecting the cardiac conduction system. By 14 day postinfection, enzymatic biomarkers of tissue damage indicated that muscle injury was decreased by SB-431542 treatment, with significantly lower blood levels of aspartate aminotransferase and creatine kinase. In conclusion, inhibition of TGF-beta signaling in vivo appears to potently decrease T. cruzi infection and to prevent heart damage in a preclinical mouse model. This suggests that this class of molecules may represent a new therapeutic agent for acute and chronic Chagas' disease that warrants further clinical exploration.

Hepatic Indicators of Oxidative Stress and Tissue Damage Accompanied by Systemic Inflammation in Rats Following a 24‐Hour Infusion of an Unstable Lipid Emulsion Admixture

Use of lipid emulsions in parenteral nutrition therapy is an important source of daily energy in substitution of potentially harmful glucose calories when given in excess in the intensive care unit. When added to parenteral nutrition (PN) admixtures as a total nutrient admixture (TNA), the stability and safety of the emulsion may be compromised. Development of a rat model of a stable vs unstable lipid infusion would enable a study of the potential risk. Prospective, randomized, controlled study. Surgical placement of a jugular venous catheter for the administration of TNAs was performed. Two groups were studied: a stable or s-TNA (n = 16) and an unstable or u-TNA (n = 17) as a 24-hour continuous infusion. Stability of TNAs was determined immediately before and after infusion using a laser-based method approved by the United States Pharmacopeia. Blood levels of aspartate aminotransferase, glutathione-S-transferase, and C-reactive protein were significantly elevated in u-TNA vs s-TNA (P < .05). Also, liver tissue concentrations of malondialdehyde were significantly higher in the u-TNA group (P < .05), and triglyceride tissue levels were also higher in u-TNA and approached statistical significance (P = .077). Unstable lipid infusions over 24 hours produce evidence of hepatic accumulation of fat associated with oxidative stress, liver injury, and a low-level systemic inflammatory response.

Hepatoprotective Effect of Vitamin B12 on Dimethylnitrosamine-Induced Liver Injury

Vitamin B(12) contains a cobalt complex and accumulates at high levels in the liver. Vitamin B(12) was examined for its hepatoprotective effect on dimethylnitrosamine-induced liver injury in mice. Vitamin B(12) decreased the blood levels of aspartate aminotransferase and alanine aminotransferase, and clearly inhibited the overaccumulation of collagen fibrils. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of the liver showed that the gene expression of alpha-smooth muscle actin and heat-shock protein 47, which are markers of fibrosis, were suppressed by vitamin B(12) administration. Our findings indicate that vitamin B(12) could be an effective hepatoprotective agent.

Concanavalin A Protects Mice from a Lethal Inoculation of IntragastricKlebsiella pneumoniaeand Reduces the Induced Liver Damage

Intragastric inoculation of Klebsiella pneumoniae can cause invasive diseases, including necrosis of liver tissues and bacteremia. The effect of concanavalin A (ConA) on K. pneumoniae was tested. Pretreatment with ConA was able to protect mice from K. pneumoniae infection in an intragastric model. K. pneumoniae-induced mouse death and liver injury such as liver necrosis, as well as blood levels of aspartate aminotransferase and alanine aminotransferase, were inhibited in a dose-dependent manner by ConA. ConA administered intravenously as late as 24 h after K. pneumoniae inoculation was still protective. In an in vitro assay, ConA was able to bind K. pneumoniae cells directly and further agglutinate them but had no effect on their in vitro growth. Surveys of bacterial counts of ConA-treated mice revealed that the bacteria were eliminated effectively in both blood and liver tissues. Furthermore, the bactericidal activity of macrophages against K. pneumoniae was also enhanced in a dose-dependent manner by ConA in an in vitro culture. These data suggest that ConA is a potentially therapeutic agent for K. pneumoniae-induced liver infection.

Test validity of periodic liver function tests in a population of Japanese male bank employees

The validity (sensitivity and specificity) of annual liver function tests, determined by assaying blood levels of aspartate aminotransferase, alanine aminotransferase and gammaglutamyl transpeptidase, was evaluated using the results of health checkups of male bank workers. The specificity of each liver function test to detect persons with fatty liver, excess alcohol users, and hepatic virus carriers, diagnosed respectively by ultrasound, detailed inquiry, and virus marker tests, was always higher than 80%, except for alanine aminotransferase in excess alcohol users (63.5%). However, the highest sensitivity to detect virus carriers was alanine aminotransferase to detect HCV antibody-positive workers, but it was only 45.5%. The highest sensitivity of the liver function tests to detect excess alcohol users in obese subjects was only 33.3%. The highest sensitivity by liver function tests to detect fatty liver was 35.7% which was inferior to that of the body mass index. These results indicate that the liver function tests mandated in the workplace periodic health checkups in Japan exhibit very low sensitivity for the detection of any of the proposed target clinical conditions.