Decrease In Ammonia Levels Research Articles

Real-World Experience of Carglumic Acid for Methylmalonic and Propionic Acidurias: An Interim Analysis of the Multicentre Observational PROTECT Study.

Methylmalonic aciduria (MMA) and propionic aciduria (PA) are organic acidurias characterised by the accumulation of toxic metabolites and hyperammonaemia related to secondary N-acetylglutamate deficiency. Carglumic acid, a synthetic analogue of N-acetylglutamate, decreases ammonia levels by restoring the functioning of the urea cycle. However, there are limited data available on the long-term safety and effectiveness of carglumic acid. Here, we present an interim analysis of the ongoing, long-term, prospective, observational PROTECT study (NCT04176523), which is investigating the long-term use of carglumic acid in children and adults with MMA and PA. Individuals with MMA or PA from France, Germany, Italy, Norway, Spain, Sweden and the UK who have received at least 1 year of carglumic acid treatment as part of their usual care are eligible for inclusion. The primary objective is the number and duration of acute metabolic decompensation events with hyperammonaemia (ammonia level >159 µmol/L during a patient's first month of life or >60 µmol/L thereafter, with an increased lactate level [> 1.8 mmol/L] and/or acidosis [pH < 7.35]) before and after treatment with carglumic acid. Peak plasma ammonia levels during the last decompensation event before and the first decompensation event after carglumic acid initiation, and the annualised rate of decompensation events before and after treatment initiation are also being assessed. Secondary objectives include the duration of hospital stay associated with decompensation events. Data are being collected at approximately 12 months' and 18 months' follow-up. Of the patients currently enrolled in the PROTECT study, data from ten available patients with MMA (n = 4) and PA (n = 6) were analysed. The patients had received carglumic acid for 14-77 (mean 36) months. Carglumic acid reduced the median peak ammonia level of the total patient population from 250 µmol/L (range 97-2569) before treatment to 103 µmol/L (range 97-171) after treatment. The annualised rate of acute metabolic decompensations with hyperammonaemia was reduced by a median of - 41% (range - 100% to + 60%) after treatment with carglumic acid. Of the five patients who experienced a decompensation event before treatment and for whom a post-treatment rate could be calculated, the annualised decompensation event rate was lower after carglumic acid treatment in four patients. The mean duration of hospital inpatient stay during decompensation events was shorter after than before carglumic acid treatment initiation in four of five patients for whom length of stay could be calculated. In this group of patients with MMA and PA, treatment with carglumic acid for at least 1 year reduced peak plasma ammonia levels in the total patient population and reduced the frequency of metabolic decompensation events, as well as the duration of inpatient stay due to metabolic decompensations in a subset of patients. ClinicalTrials.gov, NCT04176523. Registered 25 November, 2019, retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04176523 .

Serum ammonia variation predicts mortality in patients with hepatitis B virus-related acute-on-chronic liver failure.

Hyperammonemia is critical to the development of hepatic encephalopathy (HE) and is associated with mortality in end-stage liver disease. This study investigated the clinical value of ammonia variation in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients. A total of 276 patients with HBV-ACLF were retrospectively recruited. Patients' ammonia levels were serially documented. Baseline ammonia, Peak ammonia (highest level), and Trough ammonia (lowest level) were particularly corrected to the upper limit of normal (AMM-ULN). The primary endpoint was 28-day mortality. The 28-day, 3-month, and 12-month mortality rates were 19.2, 25.7, and 28.2%, respectively. A total of 51 (18.4%) patients had overt HE (grade 2/3/4). Peak AMM-ULN was significantly higher in patients with overt HE and non-survivors compared with their counterparts (P < 0.001). Following adjustment for significant confounders, high Peak AMM-ULN was an independent predictor of overt HE (hazard ratio, 1.031, P < 0.001) and 28-day mortality (hazard ratio, 1.026, P < 0.001). The cut-off of Peak AMM-ULN was 1.8, determined by using the X-tile. Patients with Peak AMM-ULN appearing on days 1-3 after admission had a higher proportion of overt HE and mortality compared to other groups. Patients with decreased ammonia levels within 7 days had better clinical outcomes than those with increased ammonia. Serum Peak ammonia was independently associated with overt HE and mortality in HBV-ACLF patients. Serial serum ammonia may have prognostic value.

Dietary Wood and Activated Charcoal Improved Ammonium Removal, Heavy Metals Detoxification, Growth Performance, Blood Biochemistry, Carcass Traits, and Histopathology of European Seabass.

A 120-day growth trial was completed to assess rearing water quality and fish performance in terms of growth, feed efficacy, digestive enzymes, immunity, and antioxidant activity of seabass fed an experimental diet (ED) supplemented with commercial wood charcoal (WC) and activated wood charcoal (AC). Three levels (0, 10, and 20 g) of WC and AC were administered, representing five treatments: control (CD) fish-fed ED without additives, (WC-1) fish-fed ED containing 10 g kg-1 WC, (WC-2) fish-fed ED containing 20 g kg-1 WC, (AC-1) fish-fed ED containing 10 g kg-1 AC, and (AC-2) fish-fed ED containing 20 g kg-1 AC. Three hundred fish (60.12 ± 0.20 g/fish) were stocked in 15 cement tanks (4.0 m × 2.0 m × 1.2 m, water volume 5 m3 each) at 20 fish/tank and a daily feed ration of 3% of body weight. Results revealed significant improvements with increased growth variables (final weight, weight gain, and specific growth rate), decreased FCR, and decreased ammonia levels and heavy metals (Cu, Cd, Fe, Mn, and Zn) content in rearing water, muscle, and liver with fish fed WC and AC supplemented diets. Furthermore, considerable improvements in digestive enzymes, immunity, and antioxidant activity, with enhanced kidneys, liver, intestines, gills, and spleen. Fish fed the WC-1 diet had a higher final weight (171.90 g), better FCR (1.25), and improved internal organs than the other groups.

Mild post-COVID syndrome in young patients

Many COVID-19 survivors suffer from post-COVID syndrome, which significantly worsens the quality of life. Its presentation is quite diverse, with cognitive disorders being of particular importance. Liver injury due to the direct virus action and the treatment of the new coronavirus infection can persist for a long time during the recovery period and lead to hyperammonemia, which can cause cognitive disorders, including minimal hepatic encephalopathy. To study cognitive disorders in post-COVID syndrome and the possibility of their treatment with L-ornithine-L-aspartate. The study included 30 students from 18 to 24 years old who had COVID-19 and decreased attention, memory impairment, and other cognitive disorders inherent in hepatic encephalopathy of latent (grade 0) or mild (grade 1) severity, without pronounced impairment of intelligence, memory, speech, and learning ability. Hyperammonemia, elevated alanine aminotransferase, aspartate aminotransferase, and ã-glutamyl transpeptidase, signs of hepatic encephalopathy according to psychometric tests, were reported in young people. All patients in the study were treated with L-ornithine-L-aspartate to correct the ammonia blood level and improve signs of hepatic encephalopathy and the general condition. An improvement in the objective findings, liver enzymes, a decrease in ammonia level, and an improvement in testing results for changes in cognitive functions were reported.

PENGARUH PEMBUBUHAN KAPORIT TERHADAP PARAMETER PH DAN AMONIA EFFLUENT PENGOLAHAN AIR LIMBAH RUMAH SAKIT

Water pollution from hospitals comes from waste water; one of the parameters that disturbs aesthetics is ammonia. Ammonia comes from the process of reforming amino acids by aerobic and anaerobic bacteria. One of the ammonia treatment is the chlorination method. The purpose of this study was to reduce the ammonia level of hospital wastewater using the chlorination method. Chlorination is used using hypochlorous acid (HOCl-) or chlorine. The chlorine dose used in the study was 2 mg / l, 4 mg / l, 6 mg / l, 8 mg / l and 10 mg / l. Data analysis using Complete Randomized Design using one way ANOVA Test. The results of research conducted on hospital ammonia wastewater showed that there was an effect of chlorine dose on ammonia levels. Chlorine dose which is quite effective in reducing ammonia levels in the study was 10 mg / l. the effectiveness of this dose can reduce ammonia by 14.08%. The test results obtained there were significant differences in the decrease in ammonia levels in each dose of chlorine with a p value of 0,000 &lt;α = 0,005

Current Management of Hepatic Encephalopathy: A Review Article

Hepatic encephalopathy, a neuropsychiatric syndrome stemming from liver failure, manifests in acute and chronic cases. The prevailing cause behind its development involves the neurotoxicity resulting from elevated ammonia levels in the brain, which can occur due to increased ammonia production or impaired ammonia excretion. The main objective in treating hepatic encephalopathy is to decrease ammonia levels. The detoxification of ammonia in this condition is regulated by two enzymes: glutaminase and glutamine synthetase. Numerous drugs, such as lactulose, rifaximin, BCAA, LOLA, glycerol phenylbutyrate, and zinc, have been utilized to treat hepatic encephalopathy. In terms of future research, experimental treatment options like fecal microbiota transplant, probiotics, bromocriptine, minocycline, indomethacin, ibuprofen, and flumazenil warrant investigation. Furthermore, albumin infusions have been shown to enhance cognitive function and improve the psychosocial quality of life, possibly by alleviating endothelial dysfunction in patients with minimal hepatic encephalopathy or previous episodes of hepatic encephalopathy. This review article offers a comprehensive overview of the current management strategies for hepatic encephalopathy.

A meta-analysis of microbiome therapies for hepatic encephalopathy.

Microbiome therapies may be reported to be effective in hepatic encephalopathy (HE). We thus did a meta-analysis of randomized controlled trials to assess the effect of microbiome therapies for HE. We systematically searched PubMed, Web of Science, EMBASE, and Cochrane Library for randomized controlled trials that compared the different treatments for HE including probiotics, symbiotics, and fecal microbiota transplant (FMT). Meta-analysis was performed to calculate pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Twenty-one studies met our inclusion criteria (N = 1746 participants). Probiotics, synbiotics and FMT significantly reversed minimal HE (MHE) (OR: 0.41, 95% CI: 0.19-0.90, P = 0.03), reduced overt HE (OHE) development (OR, 0.41; 95% CI: 0.28-0.61 P < 0.00001)and the frequency of serious adverse events(SAEs) (OR:0.14, 95% CI: 0.04-0.47, P = 0.001), meanwhile decreased ammonia levels (WMD: -9.26, 95% CI: -16.92 to -1.61; P = 0.02), NCT level (MD = -4.41, 95% CI: -0.87 to -0.22, P = 0.04) and hospitalization rates (OR, 0.38; 95% CI: 0.19-0.79, P = 0.009) compared with placebo/no treatment. Finally, we conclude that microbiome therapies were more effective in improving MHE and preventing progression to OHE, reducing the frequency of SAEs, and decreasing ammonia levels, NCT level, and hospitalization rates when compared to placebo/no treatment.

Penambahan feed additive tepung daun kelor (Moringa oleifera) untuk mitigasi amonia terhadap kualitas karkas dan lemak abdominal ayam broiler

The purpose of this study was to determine the addition of feed additive (Moring oleifera) leaf flour to mitigation ammonia on carcass quality and abdominal fat of broiler chickens. This research method used a completely randomized design (CRD) with 4 treatments and 5 replications and each experimental used 10 broilers. The treatments used were P0 (feed control without the addition of Moringa leaf flour), P1 (feed with the addition of 3 g/kg Moringa leaf flour, P2 (formulation ration with the addition of 6 g/kg Moringa leaf flour) P3 (formulation ration with the addition of 9 g/kg Moringa leaf flour) given at the finisher phase (age 15-35). Parameters were amonia levels, body weight, carcass weight, percentage of the carcass, and percentage of abdominal fat. The results of this study showed that the addition of Moringa leaf flour feed additive to a level (9 g/kg) had a significant effect (P&lt;0.05) on reducing ammonia levels and did not have a significant effect on (P&gt;0.05) on body weight, body weight, and body weight. carcass, percentage of the carcass, and percentage of abdominal fat. However, adding moringa leaf flour can decrease ammonia levels without unaffected body weight, body weight, and body weight. carcass, percentage of the carcass, and percentage of abdominal.

S3430 Lactulose Works in the Large Bowel: But How Does It Improve Hepatic Encephalopathy in a Patient Without a Large Bowel?

Introduction: Lactulose is a non-absorbable disaccharide which acts in the large bowel, and is commonly used in the treatment of hepatic encephalopathy. We present an interesting case of altered mental status due to hepatic encephalopathy successfully managed with lactulose in a patient with history of total colectomy. Case Description/Methods: A 67-year-old male with non-alcoholic cirrhosis and inflammatory bowel disease (IBD) post total proctocolectomy with a continent ileostomy known as a “Kock-pouch” (K-pouch) presented to the hospital with flu like symptoms and altered mental status. He was subsequently found to be positive for COVID-19. At the time of initial evaluation, the patient was obtunded with an elevated ammonia level of 91 umol/L. Colorectal surgery was consulted as the patient was not able to empty his K-pouch. Recently, he complained of inability to catheterize and with bleeding from the stoma. Initial catheterization with a Water’s tube yielded 400 cc of effluent. Nasogastric tube was placed through which he was receiving lactulose 30 mg q8 hours. The patient’s mental status improved within 24 hours. The patient ultimately underwent flexible pouchoscopy with endoscopic dilation and placement of a 22 French mushroom catheter for decompression of the K-pouch. Discussion: Lactulose is a non-absorbable disaccharide composed of galactose and fructose. The small intestine does not have the enzymes required to breakdown lactulose so it reaches the large bowel in its original form. In the large bowel, it is metabolized by colonic bacteria into monosaccharides and then to volatile fatty acids, hydrogen and methane. Lactulose decreases both the production and absorption of ammonia mainly through the presence of gut bacteria. The question arises as to how lactulose decreased ammonia levels in this patient without a large bowel. One proposed mechanism is the translocation of bacteria normally found in the large bowel to the small intestine. Small Intestinal Bacterial Overgrowth (SIBO), is a condition causing an increased number of bacteria in the small intestine. Patients with IBD and structural abnormalities are at increased risk of developing SIBO. Lactulose is commonly used in the diagnosis through the administration of lactulose and subsequent measurements of hydrogen and methane gas in expired air. This condition, in our patient with history of ulcerative colitis and colectomy, is a proposed mechanism of the efficacy of lactulose in the treatment of hepatic encephalopathy.

Potential Utilization of &lt;i&gt;Brevundimonas diminuta&lt;/i&gt; to Reduce Ammonia in Wastewater

Ammonia is a harmful substance on wastewater if discharged to the river, then it must be treated well. This research was aimed to examine the potential for the type of bacteria Brevundimonas diminuta in the ammonia degradation process of wastewater. Earlier step was done to examine bacteria growth in synthetical medium of ammonia concentration ranged 5 – 25 ppm. It shows that the bacteria could grow well within that ranges. Then, the bacteria performances were examined to grow in wastewater sampled from Musi River containing ammonia ranged 1.9 – 2.94 mg/L in the airlift bioreactor. The wastewater used in bioreactor was 1 L. Air was injected into the bioreactor with variations in the air flow rate of 1.5 to 4.5 L/m and with varying observation times from 1.5 to 6 hours. The optimal decrease in ammonia levels has occurred when the air flow rate was 3 L/min for 6 hours and the ammonia level was reduced from 2.94 mg/L to 1.76 mg/L.

Association Between Continuous Kidney Replacement Therapy Clearance and Outcome in Pediatric Patients With Hyperammonemia Not Due to Inborn Error of Metabolism.

To describe a single-center experience of pediatric patients with hyperammonemia not due to inborn errors of metabolism and determine the association between use of continuous kidney replacement therapy (CKRT) treatment and outcomes. Retrospective cohort study. Tertiary-care children's hospital. All children less than 21 years old admitted to the hospital with hyperammonemia defined as an elevated ammonia levels (>100 µmol/L) not due to inborn error of metabolism. None. Of 135 children with hyperammonemia, the most common reason for admission was infection in 57 of 135 (42%), congenital heart disease in 20 of 135 (14%), and bone marrow transplantation in 10 of 135 (7%). The overall mortality was 61% (82 of 135), which increased with degree of hyperammonemia (17 of 23 [74%] in those with ammonia >250 µmol/L). After multivariable regression, hyperammonemia severity was not associated with mortality (aOR, 1.4; 95% CI, 0.92-2.1; p = 0.11). Of the 43 patients (32%) receiving CKRT, 21 were prescribed standard clearance and 22 high clearance. The most common indications for CKRT were fluid overload in 17 of 43 (42%) and acute kidney injury or uremia in 16 of 43 (37%). Mean CKRT duration was 13 days. There was no difference between standard and high clearance groups in risk of death (76% vs 86%; p = 0.39), cerebral edema on CT scan (19% vs 27%; p = 0.52), nor decrease in ammonia levels after 24 or 48 hours of CKRT ( p = 0.20, p = 0.94). Among those receiving CKRT, we failed to find an association between high clearance and decreased risk of death in multivariable analysis (aOR, 1.2; 95% CI, 0.64-2.3; p = 0.55). In our single-center retrospective study, we failed to find an association between clearance on CKRT and improved survival nor decreased cerebral edema on head imaging. In fact, we failed to find an association between ammonia level and mortality, after controlling for illness severity.

Potential Carbon Thickness on Ammonia Content in Nile Tilapia (Oreochromis niloticus) Aquaponics System with Water Spinach (Ipomoea aquatica)

The application of aquaponics aquaculture is needed to improve water quality, especially the addition of filtration materials which act as absorbent planting mediums for ammonia nitrogen content in toxic water. The purpose of the current study was to determine the effect of the carbon thickness on ammonia levels in Nile tilapia in aquaponics systems with Water spinach. The study used an experimental method with a completely randomized design consisting of four treatments and five replications. The main parameter was ammonia level. Supporting parameters in this study included initial and final growth of Water spinach, fish survival rate, specific growth rate, and water quality which included temperature measurement, dissolved oxygen, and pH. Each treatment consisted of variations of carbon thicknesses at P0 (control), P1 (5 cm), P2 (7 cm), and P3 (9 cm). The results revealed that ammonia levels were significantly different at P1, P2, and P3 in the third and fourth weeks. Ammonia levels during the study decreased from 0.3969 ppm to 0.1741 ppm. The reported value of 7.2 was for acidity degree, 29.3°C for the temperature, 5.94 ppm for dissolved oxygen, 8.42 cm for the growth of Water spinach, 0.44% for the specific growth rate, and 90% for the survival rate. Carbon thickness caused a decrease in ammonia levels in Nile tilapia with aquaponics systems through the medium of Water spinach.

Pemanfaatan Mikroalga dalam Penurunan Kadar Amonia dengan Variasi Penambahan Effective Microorganism

The existence of microalgae in water -provides many benefits especially for biological treatments of wastewater. Microalgae have many species and are chlorophyll microorganisms. Photosynthesis carried out by microalgae requires essential nutrients such as CO2. Carbon dioxide can be obtained by symbiosis from other microorganisms, such as EM4, which can be used to decompose complex organic compounds into simple compounds (CO2). The addition of EM4 must be appropriate to make the photosynthesis process in microalgae take place optimally. Therefore, this study aims to determine the optimal dose variation of EM4 in the microalgae in the reactor. With variations in the doses tested were 0 mL, 1 mL, and 2 mL. The research was conducted by making artificial wastewater from liquid NPK, diluting it with tap water with a ratio of 1: 300. The test was carried out using a batch system, with solar lighting and aeration for 24 hours. The result of the best dose variation is the addition of 1 mL of EM4. The largest decrease in ammonia levels is obtained which is then compared to the variation of the doses of 0 mL and 2 mL.

Transient hyperammonaemia following epileptic seizures in cats

The aim of this study was to determine whether transient postictal hyperammonaemia exists in cats. The medical records of all feline patients that presented at a Swedish veterinary hospital between 2008 and 2018 were retrospectively reviewed to find those that had a recent or ongoing epileptic seizure. To qualify for inclusion, the medical record had to include information on at least one ammonia value taken in close proximity to, or during, an active seizure, the cat must have exceeded the normal upper limit of blood ammonia concentration on initial testing (reference interval 0-95 μmol/l), and there needed to be a follow-up ammonia value available within a maximum of 3 days. Five cats were included in the study, and they had blood ammonia concentrations on initial testing ranging from 146 to 195 µmol/l. They were all retested within a period of 2 h to 3 days of the original reading. All five cats had a spontaneous decrease in ammonia levels without any specific treatment for hyperammonaemia. Pursuant to the findings of this retrospective study, transient hyperammonaemia may be noted after epileptic seizure in cats. Consequently, a differential diagnostic list in feline patients with hyperammonaemia could, depending on the context, include non-hepatic-related pathologies, such as epileptic seizures.

PEMANFAATAN KARBON AKTIF DARI TEMPURUNG KELAPA DALAM MENURUNKAN KADAR AMONIA TOTAL DALAM AIR LIMBAH INDUSTRI

Entering the industry 4.0 stage, more industries are developing in Indonesia, one of which is PT Puradelta Lestari. PT Puradelta Lestari as a developer of the Deltamas city area that serves industrial, commercial and residential customers produces industrial liquid waste. Preliminary studies have shown that the ammonia content of wastewater in the PT has exceeded the threshold of 25 mg / L amonia. This study aims to determine the effect of adding activators to activated carbon from coconut shells with variations of immersion time on decreasing total ammonia levels in wastewater at PT. Puradelta Lestari. Activation of activated carbon is carried out with activators HCl, NaCl, and KOH with a concentration of 4%, with a volume ratio of activator 1: 6 and variations in the immersion time for 12 hours, 16 hours, 20 hours, 24 hours. The optimum condition was obtained at the time of immersion with KOH activator for 24 hours obtained a decrease in ammonia levels that is equal to 87.6%.

IMMOBILISASI SUSPENSI AKTIF PADA PELLET AMMONIA OXIDIZERS UNTUK PENGOLAHAN LIMBAH URIN KAMBING MENJADI PUPUK N

Livestock waste that is thrown away without being processed will cause environmental pollution, therefore an effort is needed to process the livestock waste is to be processed into organic fertilizer. The part of livestock waste that can be used as organic fertilizer is urine, in this study goat urine is used. This study aims to find the best nutrients for seeding active suspension, look for the optimal dosage and time for processing goat urine into N fertilizer. The method used in this study is to immobilized the active suspension into the ammonia oxidizers pellets for later used in the goat urine treatment process with an aeration system, so that a nitrification reaction occurs which results is decrease ammonia and nitrite levels and increase nitrate levels. The results obtained in this study are the nutrients that are best used for seeding active suspension are media II that is 5 grams NPK fertilizer; 2,5 grams NH4Cl; and 5 grams glucose with MLVSS values ??of 9000 mg/L at 18 hours. The processing of goat urine obtained optimal results at pellet dosage of 20% (w/v) with optimal time at 18th hour. Ammonia level obtained was 5.6811 mg/L, nitrite levels of 2.3992 mg/L, and nitrate levels of 10.6618 mg/L. &#x0D; Keywords: Immobilization; active suspension; MLVSS; pellets; ammonia oxidizers; nitrification

BabaoDan cures hepatic encephalopathy by decreasing ammonia levels and alleviating inflammation in rats.

BabaoDan (BBD) is a famous traditional Chinese formula frequently used in TCM clinics to eliminate jaundice and treat infectious viral hepatitis. This paper assesses BBD's preventive and therapeutic effects on hepatic encephalopathy after liver cirrhosis (CHE) and acute liver failure (AHE) in rats and explains its possible mechanism of action. CHE rat model was established by injection of carbon tetrachloride (CCl4) twice a week for a total of 9 weeks and then by injection of thioacetamide (TAA) to induce hepatic encephalopathy. AHE rat model was established by injection of TAA once a day for a total of 3 days. In CHE rat model, BBD was gavaged once a day at the end of the 6th week until the experiment ended. In AHE rat model,BBD was gavaged once a day 3 days before TAA injection until the experiment ended. The preventive and therapeutic effects of BBD on brain dysfunction, as well as liver injury, pathology and fibrosis were evaluated in vivo. The role of BBD in the regulation of inflammatory factors and myeloid differentiation factor 88/Toll-like receptor 4/nuclear factor kappa-B (TLR4/MyD88/NK-κ B) pathway was detected in both liver and brain in vivo. The rat bone marrow derived macrophages (BMDMs) were activated by Lipopolysaccharide (LPS), and the role of BBD in the regulation of inflammatory factors and NK-κ B pathway were detected in vitro. In CHE rat model: BBD significantly improved the total distance as well as the activity rate of rats. BBD also improved the learning and memory abilities of rats compared with the control group. In addition, BBD effectively decreased ammonia levels and significantly decreased the levels of alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBil) and total bile acid (TBA), as well as improved the levels of total protein (TP) and albumin (Alb). In the liver, BBD not only inhibited the gene expressions of tumor necrosis factor alpha (TNF-α), interleukini-6 (IL-6), TLR4, MyD88, and NF-κ B but also inhibited the protein expressions of TLR4, MyD88, NK-κ B and TNF-α. In the brain, BBD inhibited the gene expressions of iNOS, IL-6, TNF-α, TLR-4, MyD88, and NF-κ B, as well as inhibited the protein expressions of TLR4, MyD88, P65 TNF-α and ionized calcium binding adapter molecule 1 (Iba-1). BBD also decreased NO and TNF-α in the blood. BBD improved neurological scores, blood ammonia levels and the brain inflammatory gene expressions of iNOS, TNF-α and IL-1β. BBD also improved liver function biomarkers such as ALT, TBil, TBA, TP, ALB and inflammatory and apoptotic gene expressions of TNF-α, IL-1β, IL-6, Bax, Bcl-2, caspase-9, caspase-3 and NF-κ B. In LPS-activated rat BMDMs, BBD decreased NO and TNF-α production in BMDM culture supernatant. In addition, BBD inhibited the gene expressions of TNF-α, IL-1 β and IL-6 as well as the phosphorylation of P65. BBD can prevent and cure hepatic encephalopathy (HE) derived from both chronic and acute liver diseases. BBD can reduce hyperammonemia as well as the systematic and neurological inflammation. Inflammation is likely an important target of BBD to treat HE. The anti-inflammatory role of BBD may lie in its regulation of the TLR4/MyD88/NF-κ B pathways.

Impact of continued administration of tolvaptan on cirrhotic patients with ascites

BackgroundThe vasopressin V2-receptor antagonist tolvaptan is used to treat cirrhotic patients with ascites. We investigated the outcome of long-term treatment.MethodsThis was a single-center retrospective study. Overall, 170 cirrhotic patients (95 males, median age 63 years) were enrolled and received tolvaptan orally after hospitalization for ascites, which included treatment with conventional diuretics. We compared patients who withdrew tolvaptan treatment after < 1 year (n = 90) with patients who continued treatment for ≥1 year (n = 37). In continuously treated patients, the pretreatment and post-treatment (1 year) blood biochemistry values were assessed.ResultsOverall, 37 patients received treatment for ≥1 year and showed a higher response after tolvaptan therapy. The reduction in body weight was 2.0 (− 3.4–17.2) kg compared to discontinued cases, which had a body weight reduction of 1.1 (− 6.2–7.5) kg after 1 week. The group that received treatment for ≥1 year had a significantly lower rate of the complication gastroesophageal varices and also showed better liver function. In patients with continued treatment, serum levels of albumin was significantly higher without renal disturbance after 1 year of treatment. The prothrombin time/international normalized ratio and ammonia level were also significantly improved. Multivariate analyses showed that a change in body weight reduction and serum levels of albumin were predictive factors of continued administration.ConclusionsLong-term tolvaptan treatment increased serum levels of albumin, decreased ammonia levels, and preserved renal function after 1 year of treatment. A reduction in body weight after 1 week was associated with a favorable outcome of tolvaptan therapy.

Plasma Glucose Level Is Predictive of Serum Ammonia Level After Retrograde Occlusion of Portosystemic Shunts.

The purpose of this study was to evaluate predictors of reduction in ammonia levels by occlusion of portosystemic shunts (PSS) in patients with cirrhosis. Forty-eight patients with cirrhosis (21 women, 27 men; mean age, 67.8 years) with PSS underwent balloon-occluded retrograde transvenous obliteration (BRTO) at one institution between February 2008 and June 2014. The causes of cirrhosis were hepatitis B in one case, hepatitis C in 20 cases, alcohol in 15 cases, nonalcoholic steatohepatitis in eight cases, and other conditions in four cases. The Child-Pugh classes were A in 24 cases, B in 23 cases, and C in one case. The indication for BRTO was gastric varices in 40 cases and hepatic encephalopathy in eight cases. Testing was conducted before and 1 month after the procedure. Statistical analyses were performed to identify predictors of a clinically significant decline in ammonia levels after BRTO. Occlusion of PSS resulted in a clinically significant decrease in ammonia levels accompanied by increased portal venous flow and improved Child-Pugh score. Univariate analyses showed that a reduction in ammonia levels due to BRTO was significantly related to lower plasma glucose levels, higher RBC counts, and higher hemoglobin concentration before the treatment. Furthermore, multivariate logistic regression identified preoperative plasma glucose level as the strongest independent predictor of a significant ammonia reduction in response to BRTO. In addition, although BRTO resulted in significantly declined ammonia levels in patients with normal glucose tolerance before the procedure, ammonia levels were not significantly decreased after shunt occlusion in patients with diabetes mellitus or impaired glucose tolerance before BRTO, according to 75-g oral glucose tolerance test results. Preoperative plasma glucose level is a useful predictor of clinically significant ammonia reduction resulting from occlusion of PSS in patients with cirrhosis. Even if PSS are present, control of blood ammonia levels by BRTO alone may be difficult in patients with glucose intolerance.

‘All that glitters is not gold’: when hyperammonaemia is not from hepatic aetiology

Hyperammonaemia is often caused by decompensated liver disease. However, non-hepatic causes can sometimes result in hyperammonaemia, severe enough to cause symptoms.We report a case of a 65-year-old man with a...