Blood Ammonia Levels Research Articles

Serum zinc levels as predictors of covert hepatic encephalopathy in patients with liver cirrhosis.

Covert hepatic encephalopathy (CHE) significantly impacts the quality of life and prognosis in patients with liver cirrhosis. This study aims to analyze the prevalence and risk factors of CHE to identify high-risk patients who would benefit from therapeutic interventions. This single-center, retrospective observational study included 126 patients without a history of overt hepatic encephalopathy (OHE). CHE was defined as a score above the age-based cutoff value in the Stroop test. Factors associated with the occurrence of CHE and the subsequent development of OHE were evaluated. CHE was detected in 47 patients (37.3%). A multiple logistic regression analysis identified serum zinc levels (per + 1µg/dL, odds ratio 0.95, P = 0.0007) as the only risk factor associated with CHE, with a cutoff value of 60µg/dL (AUC 0.71, P = 0.0001). Neither blood ammonia levels nor liver function were predictive of CHE. During a median observation period of 211days, OHE developed in 18 patients (14.3%). The administration of more than 20mg of furosemide was identified as a risk factor for developing OHE (hazard ratio 23.52, P = 0.0207). Cirrhotic patients with serum zinc levels below 60µg/dL exhibit a high risk of developing CHE, regardless of blood ammonia levels. These patients face a significant risk of developing OHE. Therefore, early zinc supplementation is recommended for the prevention of OHE, particularly for those prescribed 20mg or more of furosemide.

An observational pilot study on Sidma kushta in relation to Yakrit & Pliha as moola sthana of Raktavaha srotas

Acharya Charaka has mentioned fifteen koshtanga in the shareera. Koshtanga refers to the viscera. Two koshtanga, Yakrit and Pliha, have been designated as the moola sthana (primary centres of physiological activity) of the Raktavaha srotas (haemopoiesis). The description of Yakrit & Pliha corresponds to the functions of the liver and spleen in contemporary anatomy. Kushta (skin disease) is a Rakta prodashaja vikara (disease caused due to the vitiation of blood). Sidma Kushta, or psoriasis, is one of the eighteen kushta listed in the Samhita. Its prevalence in the Indian population ranges from 0.44 to 2.8%. Recent observational studies have shown that the prevalence of NAFLD [Non-Alcoholic Fatty Liver Disease] (as diagnosed either by imaging or by histology) is remarkably higher in psoriatic patients (occurring in up to 50% of these patients) and suggested the presence of a novel hepato dermal axis. In this pilot study, six individuals diagnosed with sidma kushta were subjected to ultrasonography of the abdomen & selected biochemical assays on the function of the liver, to observe the relationship between sidma kushta and moola sthana of raktavaha srotas.The data was statistically analyzed using Spearman’s correlation coefficient and a correlation was observed between the fatty liver grade and the levels of ALT, AST, and blood ammonia.

Right liver lobe diameter to serum albumin ratio and blood ammonia level as non-invasive predictor for the presence of esophageal varices and the risk of bleeding in patient of cirrhosis of liver

Right liver lobe diameter to serum albumin ratio and blood ammonia level as non-invasive predictor for the presence of esophageal varices and the risk of bleeding in patient of cirrhosis of liver

High Blood Ammonia Level Is a Predictor of Medium and Large Size Esophageal Varices In Cirrhotic Patients

Background: The development of esophageal varices (EV) and rupture of them are the most serious complications of portal hypertension. Upper gastrointestinal endoscopy is the gold standard for diagnosis of EV but it is a costly and troublesome invasive procedure. To find a non-invasive method for detection of size of EV and to predict the bleeding risk is appealing and would decrease the indications cost and discomfort of upper GI endoscopy. The aim of the study is to evaluate high blood ammonia level is a predictor of medium and large size of esophageal varices in Cirrhotic patients. Methods: This was an observational Cross-sectional study conducted on 40 cirrhotic patients in Department of Gastroenterology, BSMMU using a pre-designed data collection sheet. Information about clinical profile, laboratory parameters- blood ammonia, serum bilirubin, serum albumin, prothrombin time, and ultrasonography of abdomen, endoscopy upper GIT was collected and recorded. The collected data was analyzed by computer with the help of SPSS version 22. Statistical analysis was done by using appropriate statistical tool like Chi-square test, Student’s t- test. P value < 0.05 was considered as significant. Diagnostic efficacy of blood ammonia was calculated by using a value. Results: A total of 40 patients with cirrhosis. Mean age of cirrhotic patients were 47.47±12.98 years. Mean blood ammonia of small size EV of cirrhotic patients was 73.70±32.11 (μmol/L) and medium and large size EV was 118.3±38.37 (μmol/L) (P< .001). At the level of 78.5 (μmol/L), sensitivity and specificity of blood ammonia was 95% and 65% respectively in detection of size of EV. Conclusion: Blood ammonia estimation could be a good tool for identifying individuals with medium and large size esophageal who will need to undergo endoscopy more frequently. Bangladesh J Medicine 2024; 35: 167-172

A nomogram prediction model for individualized prediction of the risk of covert (minimal) hepatic encephalopathy occurrence in patients with liver cirrhosis

Objective: To construct an individualized nomogram prediction model for predicting the risk of the occurrence of covert hepatic encephalopathy (CHE) in patients with liver cirrhosis. Methods: 325 cases of liver cirrhosis admitted from January 2020 to December 2022 were selected as the study subjects. Patients were divided into training (n=213) and validation (n=112) sets using a cluster randomization method. The risk factors for CHE occurrence in patients with cirrhosis in the training set were analyzed by univariate and multivariate logistic regression. A prediction model related to the nomogram was established. Results: Independent risk factors for the occurrence of CHE in patients with cirrhosis were a history of hepatic encephalopathy, co-infection, gastrointestinal bleeding, severe ascites, prothrombin time ≥16 seconds, high total bilirubin, and high blood ammonia levels (P<0.05). Nomogram model validation results: The model had a net benefit for the training and validation sets, with C-indices of 0.830 (95%CI: 0.802-0.858) and 0.807 (95%CI: 0.877-0.837), respectively, within the range of 0-96%. The calibration curves of both sets were evenly close to the ideal curves. The AUCs for the ROC curves in both sets were 0.827 (95%CI: 0.796-0.858) and 0.811 (95%CI: 0.787-0.836), respectively. Conclusion: Patients with cirrhosis have many risk factors for CHE occurrence. The nomogram model constructed based on these risk factors possesses a good predictive value for assessing CHE occurrence in cirrhotic patients.

Effects of time-dependent acupuncture on back muscle endurance in women with chronic nonspecific low back pain: A randomized crossover trial.

Chronic nonspecific low back pain (CNLBP) is a leading cause of disability and remains a major burden for many public health systems. Acupuncture is a nonpharmacological treatment for CNLBP that can be effective in improving low back pain; nevertheless, its effect on improving back muscle endurance in patients with CNLBP and its duration of effect have not been studied. The goal of this study was to assess the impact of acupuncture on lower back muscle activity in CNLBP patients. This was a single-blind, randomized, crossover experimental study. Thirty female patients were randomized into Group A (15 patients) or Group B (15 patients). Patients in Group A were assigned to receive real acupuncture (RA) in the first phase and sham acupuncture (SA) in the second phase, while those in Group B received SA first and then RA, with a 1-week washout period between phases. Two-way repeated ANOVA was used to evaluate the effect of group and time on isokinetic parameters, Surface electromyography (sEMG) data, and blood data. Significant interaction effects were identified between group * time on the isokinetic parameters of the lumbar extensor muscles, sEMG values of the erector spinae, blood lactate levels, and blood ammonia levels (all p< 0.05). Compared with those of the SA group, the isokinetic parameters of the lumbar extensor muscles, sEMG values of the erector spinae, blood lactate levels, and blood ammonia levels of the RA group were significantly different (all p< 0.05). RA improves lumbar extensor endurance in patients with CNLBP and lasts approximately 9 minutes. RA can improve blood circulation to reduce blood lactic acid and blood ammonia produced during exercise.

Effect of an Autotaxin Inhibitor, 2-(4-Chlorophenyl)-7-methyl-8-pentylimidazo[1,2-a] Pyrimidin-5(8H)-one (CBT-295), on Bile Duct Ligation-Induced Chronic Liver Disease and Associated Hepatic Encephalopathy in Rats.

The role of autotaxin (ATX)-lysophosphatidic acid (LPA) is yet to be explored in the context of liver cirrhosis and associated encephalopathy. Our objective of this study was to evaluate the role of an ATX inhibitor in biliary cirrhosis and associated hepatic encephalopathy in rats. The preliminary investigation revealed significant impairment in liver function, which eventually led to the development of hepatic encephalopathy. Interestingly, LPA levels were significantly increased in the plasma, liver, and brain of rats following bile duct ligation. Subsequently, we tested the efficacy of an ATX inhibitor, CBT-295, in bile duct-induced biliary cirrhosis and neuropsychiatric symptoms associated with hepatic encephalopathy. CBT-295 showed good oral bioavailability and favorable pharmacokinetic properties. CBT-295 exhibited a significant reduction in inflammatory cytokines like TGF-β, TNF-α, and IL-6 levels, also reduced bile duct proliferation marker CK-19, and lowered liver fibrosis, as evident from reduced collagen deposition. The reversal of liver fibrosis with CBT-295 led to a reduction in blood and brain ammonia levels. Furthermore, CBT-295 also reduced neuroinflammation induced by ammonia, which is characterized by a significant reduction in brain cytokine levels. It improved neuropsychiatric symptoms such as locomotor activities, cognitive impairment, and clinical grading scores associated with hepatic encephalopathy. The improvement in hepatic encephalopathy observed with the ATX inhibitor could be the result of its hepatoprotective action and its ability to attenuate neuroinflammation. Therefore, inhibition of ATX-LPA signaling can be a multifactorial approach for the treatment of chronic liver diseases.

Clinical characteristics and molecular genetic analysis of ten cases of ornithine carbamoyltransferase deficiency in southeastern China

BackgroundThis study aimed to investigate the clinical and molecular genetic characteristics of ten children with ornithine carbamoyltransferase deficiency (OTCD) in southeastern China, as well as the correlation between the genotype and phenotype of OTCD.MethodsA retrospective analysis was performed on the clinical manifestations, laboratory testing, and genetic test findings of ten children with OTCD admitted between August 2015 and October 2021 at Quanzhou Maternity and Children’s Hospital of Fujian Province in China.ResultsFive boys presented with early-onset symptoms, including poor appetite, drowsiness, groaning, seizures, and liver failure. In contrast, five patients (one boy and four girls) had late-onset gastrointestinal symptoms as the primary clinical manifestation, all presenting with hepatic impairment, and four with hepatic failure.Nine distinct variants of the OTC gene were identified, including two novel mutations: c.1033del(p.Y345Tfs*50) and c.167T > A(p.M56K). Of seven patients who died, five had early-onset disease despite active treatment. Three patients survived, and two of them underwent liver transplantation.ConclusionsThe clinical manifestations of OTCD lack specificity. However, elevated blood ammonia levels serve as a crucial diagnostic clue for OTCD. Genetic testing aids in more accurate diagnosis and prognosis assessment by clinicians. In addition, we identified two novel pathogenic variants and expand the mutational spectrum of the gene OTC, which may contribute to a better understanding of the clinical and genetic characteristics of OTCD patients.

Changes in Plasma Concentration of Free Proteinogenic and Non-Proteinogenic Amino Acids in High-Performance Sprinters over a 6-Month Training Cycle.

Background/Objectives: Free amino acids substantially contribute to energy metabolism. Also, their profile may identify (over)training status and effectiveness. The long-term effects of speed-power training on plasma free amino acid (PFAA) profiles are not known. We aimed to observe variations in PFAA levels in high-performance sprinters in a six-month training cycle. Methods: Ten male athletes (24.6 ± 3.3 years) were examined during four training phases: transition (1 month), general preparation (2 months), specific preparation (1 month), and pre-competition/competition (2 months). Venous blood was collected at rest, after exhaustive exercise, and recovery. Forty-two PFAAs were analyzed by the LC-ESI-MS/MS method. Results: Significant decreases in resting concentrations were observed between the transition and competition phases for glutamine (762 ± 117 vs. 623 ± 53 μmol∙L-1; p < 0.001, η2 = 0.47) and histidine (89 ± 15 vs. 75 ± 10 μmol∙L-1; p = 0.010, η2 = 0.27), whereas β-alanine (30 ± 7 vs. 41 ± 9 μmol∙L-1; p = 0.024, η2 = 016) and sarcosine (3.6 ± 0.4 vs. 4.8 ± 0.6 μmol∙L-1; p = 0.006, η2 = 0.188) levels increased. Between the specific and competition phases, significant decreases in the resting levels of 1-methylhistidine (22.1 ± 19.4 vs. 9.6 ± 8.8 μmol∙L-1; p = 0.14, η2 = 0.19), 3-methylhistidine (7.1 ± 1.5 vs. 6.5 ± 1.6 μmol∙L-1; p = 0.009, η2 = 0.18), citrulline (40 ± 10 vs. 29 ± 4 μmol∙L-1; p = 0.05, η2 = 0.29), and ornithine (74 ± 15 vs. 56 ± 10 μmol∙L-1; p = 0.015, η2 = 185) were noticed. Also, for β-alanine and sarcosine, the pattern of response to exercise strongly changed between the training phases. Blood ammonia levels at exhaustion decreased between the transition and competition phases (32 ± 4 vs. 23 ± 5 μmol∙L-1; p < 0.001, η2 = 0.67), while lactate, the phenylalanine-tyrosine ratio, the glutamine-glutamate ratio, hematological parameters, and cardiorespiratory indices remained at similar levels. Conclusions: Speed-power training seems to affect PFAAs involved in skeletal muscle metabolic pathways responsible for neutralizing toxic ammonia (glutamine, arginine, citrulline, ornithine), attenuating the deleterious effects of H+ ions (histidine, β-alanine), and reducing exercise-induced protein breakdown (1- and 3-methylhistidine). Our findings suggest that sprint-oriented training supports metabolic pathways that are responsible for the removal of harmful metabolites produced during exercise.

Correlation of ammonia and blood laboratory parameters with hepatic encephalopathy: A systematic review and meta-analysis.

Emerging research suggests that hyperammonemia may enhance the probability of hepatic encephalopathy (HE), a condition associated with elevated levels of circulating ammonia in patients with cirrhosis. However, some studies indicate that blood ammonia levels may not consistently correlate with the severity of HE, highlighting the complex pathophysiology of this condition. A systematic review and meta-analysis through PubMed, Scopus, Embase, Web of Science, and Virtual Health Library were conducted to address this complexity, analyzing and comparing published data on various laboratory parameters, including circulating ammonia, blood creatinine, albumin, sodium, and inflammation markers in cirrhotic patients, both with and without HE. This comprehensive review, which included 81 studies from five reputable databases until June 2024, revealed a significant increase in circulating ammonia levels in cirrhotic patients with HE, particularly those with overt HE. Notably, significant alterations were observed in the circulating creatinine, albumin, sodium, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNFα) in HE patients. These findings suggest an association between ammonia and HE and underscore the importance of considering other blood parameters such as creatinine, albumin, sodium, and pro-inflammatory cytokines when devising new treatment strategies for HE.

Infection, inflammation and hepatic encephalopathy from a clinical perspective.

Hepatic encephalopathy (HE) is a syndrome that is associated with both acute and chronic liver injury. It manifests as a wide spectrum of neuropsychological abnormalities, ranging from subtle impairments in executive higher functions observed in cirrhosis, through to coma in acute liver failure. In acute liver failure, the central role of ammonia in the development of brain oedema has remained undisputed for 130 years. It latterly became apparent that infection and inflammation were profound determinants for the development of severe hepatic encephalopathy, associated with the development of cerebral oedema and intracranial hypertension. The relationship of the development of hepatic encephalopathy with blood ammonia levels in cirrhosis is less clear cut and the synergistic interplay of inflammation and infection with ammonia has been identified as being fundamental in the development and progression of hepatic encephalopathy. A perturbed gut microbiome and the presence of an impaired gut epithelial barrier that facilitates translocation of bacteria and bacterial degradation products into the systemic circulation, inducing systemic inflammation and innate and adaptive immune dysfunction, has now become the focus of therapies that treat hepatic encephalopathy in cirrhosis, and may explain why the prebiotic lactulose and rifaximin are efficacious. This review summarises the current clinical perspective on the roles of inflammation and infection in hepatic encephalopathy and presents the evidence base for existing therapies and those in development in the setting of acute and chronic liver failure.

Portable Sensing Probe for Real-Time Quantification of Ammonia in Blood Samples.

The detection of ammonia levels in blood is critical for diagnosing and monitoring various medical conditions, including liver dysfunction and metabolic disorders. However, traditional diagnostic methods are slow and cumbersome, often involving multiple contact-based steps such as ammonia separation in alkali conditions followed by distillation or microdiffusion, leading to delays in diagnosis and treatment. Herein, we developed a colorimetric assay capable of rapid detection of ammonia in whole blood or plasma samples, utilizing 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO)-oxidized cellulose nanocrystals (TCNC) coupled with gold nanoparticles (AuNPs). The basis of our assay relies on either (i) the interaction between the carboxylate group (-COO) of TEMPO and ammonium ions or (ii) the manipulation of AuNPs surface plasmon resonance (SPR) through the formation of Au(NH3)43+, which displaces a redox mediator, resazurin, resulting in observable multicolor displays at various concentrations of ammonia. The colorimetric assay exhibits a wide linear detection range for dissolved NH4+ (0.1-37 μM) with a low limit of detection (LOD) of 0.1 μM. Additionally, it effectively measures NH3(g) concentrations in the range of 0.5-144 μM. The fabricated electrochemical nose (E-nose) device demonstrates excellent analytical performance for plasma ammonia sensing (0.05-256 μM). Experimental results demonstrate a linear detection range suitable for clinical applications, with excellent correlation to standard laboratory methods, offering a practical solution for point-of-care (PoC) testing. We anticipate that this approach can be applied broadly to improve patient monitoring and treatment by providing immediate and accurate ammonia measurements in a clinical setting.

Clinical features and CPS1 variants in Chinese patients with carbamoyl phosphate synthetase 1 deficiency

BackgroundCarbamoyl phosphate synthetase 1 (CPS1) deficiency (OMIM 237300), an autosomal recessive rare and severe urea cycle disorder, is associated with hyperammonemia and high mortality.MethodsHerein we present 12 genetic variants identified in seven clinically well-characterized Chinese patients with CPS1 deficiency who were admitted to the Children’s Medical Center of Peking University First Hospital from September 2014 to August 2023.ResultsSeven patients (two male and five female patients including two sisters) experienced symptoms onset between 2 days and 13 years of age, and they were diagnosed with CPS1 deficiency between 2 months and 20 years. Peak blood ammonia levels ranged from 160 to 1,000 µmol/L. Three patients showed early-onset CPS1 deficiency, with only one surviving after treatment with sodium phenylbutyrate, N-carbamoyl-L-glutamate, and liver transplantation at 4 months, showing a favorable outcome. The remaining four patients had late-onset CPS1 deficiency, presenting with mental retardation, psychiatric symptoms, and self-selected low-protein diets. Among the 12 CPS1 variants identified in these patients, 10 were novel, with all patients exhibiting compound heterozygosity for CPS1 mutant alleles. Seven variants (c.149T > C, c.616 A > T, c.1145 C > T, c.1294G > A, c.3029 C > T, c.3503 A > T, and c.3793 C > T) resulted in single amino acid substitutions. Three frameshift variations (c.2493del, c.3067dup, and c.3241del) were identified, leading to enzyme truncation. One mutation (c.3506_3508del) caused an in-frame single amino acid deletion, while another (c.2895 + 2T > C) resulted in aberrant splicing.ConclusionsExcept for two known variants, all other variants were identified as novel. No hotspot variants were observed among the patients. Our data contribute to expanding the mutation spectrum of CPS1.

Validity of Serum Ammonia Level for Diagnosis of Severity of Hepatic Encephalopathy in Children

Hepatic encephalopathy is a broad spectrum neuropsychiatric abnormalities of liver dysfunction. Ammonia level may correlate with the severity of liver failure. The brain is very sensitive to the toxic effects of ammonia. As a result patient may manifests with irritability, slurring of speech, reversal of sleep-awake cycle, flapping tremor, confusion, stupor or even deep coma. This study was aimed to validate the ammonia level in children with liver failure for the assessment of its severity considering hepatic encephalopathy. This cross-sectional comparative study was conducted among 64 children aged 1-15 years of both sexes (study subjects) diagnosed as acute or acute on chronic liver failure in the Department of Pediatric Gastroenterology and Nutrition, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh during the period of November 2017 to September 2019. The subject were divided into two groups for the comparison of ammonia level to assess the severity in contrast to hepatic encephalopathy. In the first group 32 were liver failure with encephalopathy and in the second group 32 were liver failure without encephalopathy. Hepatic encephalopathy was diagnosed on the basis of West Haven Criteria. The analysis was done by the Receiver Operating Characteristic Curve with SPSS-20. Among the 64 patients female were 45% whereas male patients were 55%, male female ratio was 1.2: 1. Regarding etiology, Wilson disease was the most common cause and it was nearly two-third (65.6%) of children, cryptogenic cirrhosis was 10%, Hepatitis A was 9.4%, Autoimmune Hepatitis (AIH) was 3.10%, Hepatitis E, Hepatitis B, Hepatitis C, biliary atresia and lipid storage were 1.60% respectively. This study showed that, ammonia of ≥71 µmol/L is an indicator for presence of hepatic encephalopathy in children. The analysis by the Receiver Operating Characteristic Curve showed area under the curve (AUC) is 0.86 with upper bound 0.96 and lower bound is 0.77. It was observed that about half (48.4%) of the children had positive blood ammonia level (≥71.0 umol/L) and among the children of positive blood ammonia level most of them (80.65%) had hepatic encephalopathy and 19.35% had no encephalopathy. More than half (51.6%) children had negative (&lt;71.0 umol/L) blood ammonia level, among them 21.21% children had encephalopathy and 78.79% patients had no encephalopathy. Sensitivity of blood ammonia was found 78.1%, specificity 81.2%, positive predictive value 80.6%, negative predictive value 78.8% and accuracy 79.7%. In conclusion, high level of ammonia is found with higher grade of encephalopathy and hyperammonia is also found in liver failure without encephalopathy. Bangladesh Med J. 2023 May; 52(2): 1-5

Hyperosmolarity in children with hyperammonemia: a risk of brain herniation at the start of renal replacement therapy.

Renal replacement therapy (RRT) is used in hyperammonemia to reduce the concentration of ammonia in the blood. In the case of plasma hyperosmolarity, RRT can also rapidly decrease plasma osmolarity, which may increase cerebral edema in these patients and favor the occurrence of brain herniation. We conducted a retrospective clinical study in a tertiary care university-affiliated hospital. All patients admitted in a Pediatric Intensive Care Unit (PICU), less than 18 years old with ammonemia >150 µmol/L and who underwent RRT between January 2015 and June 2023 were included. We collected data on plasma osmolarity levels, osmolar gap and blood ammonia levels before and during RRT. Eleven patients were included (10 with acute liver failure and 1 with a urea cycle disorders). Their mean age was 36.2 months. Before RRT, the median highest measured osmolarity was 320 (305-324) mOsm/L, whereas the median calculated osmolarity was 303 (293-314) mOsm/L, corresponding to an osmolar gap of 14 mOsm/L. Ammonia blood level over 400 µmol/L are significantly associated with higher plasma osmolarity (P-Value <0.001). In one case, a patient had a brain herniation episode after a quick osmolar drop. This episode was reversed by the administration of hyperosmolar agents and the temporary suspension of RRT. This study highlights the hyperosmolarity and high osmolar gap that occur in children with hyperammonemia. A careful monitoring and control of plasma osmolarity evolution may alert clinician on the risk of occurrence of neurological complication such as brain herniation.

Effect of rest duration between sets on fatigue and recovery after short intense plyometric exercise

Plyometric training is characterized by high-intensity exercise which is performed in short term efforts divided into sets. The purpose of the present study was twofold: first, to investigate the effects of three distinct plyometric exercise protocols, each with varying work-to-rest ratios, on muscle fatigue and recovery using an incline-plane training machine; and second, to assess the relationship between changes in lower limb muscle strength and power and the biochemical response to the three exercise variants employed. Forty-five adult males were randomly divided into 3 groups (n = 15) performing an exercise of 60 rebounds on an incline-plane training machine. The G0 group performed continuous exercise, while the G45 and G90 groups completed 4 sets of 15 repetitions, each set lasting 45 s with 45 s rest in G45 (work-to-rest ratio of 1:1) and 90 s rest in G90 (1:2 ratio). Changes in muscle torques of knee extensors and flexors, as well as blood lactate (LA) and ammonia levels, were assessed before and every 5 min for 30 min after completing the workout. The results showed significantly higher (p < 0.001) average power across all jumps generated during intermittent compared to continuous exercise. The greatest decrease in knee extensor strength immediately post-exercise was recorded in group G0 and the least in G90. The post-exercise time course of LA changes followed a similar pattern in all groups, while the longer the interval between sets, the faster LA returned to baseline. Intermittent exercise had a more favourable effect on muscle energy metabolism and recovery than continuous exercise, and the work-to-rest ratio of 1:2 in plyometric exercises was sufficient rest time to allow the continuation of exercise in subsequent sets at similar intensity.

Implications of Genetic Factors Underlying Mouse Hydronephrosis: Cautionary Considerations on Phenotypic Interpretation in Genetically Engineered Mice.

Hydronephrosis, the dilation of kidneys due to abnormal urine retention, occurs spontaneously in certain inbred mouse strains. In humans, its occurrence is often attributed to acquired urinary tract obstructions in adults, whereas in children, it can be congenital. However, the genetic factors underlying hydronephrosis pathogenesis remain unclear. We investigated the cause of hydronephrosis by analyzing tetraspanin 7 (Tspan7) gene-modified mice, which had shown a high incidence of hydronephrosis-like symptoms. We found that these mice were characterized by low liver weights relative to kidney weights and elevated blood ammonia levels, suggesting liver involvement in hydronephrosis. Gene expression analysis of the liver suggested that dysfunction of ornithine transcarbamylase (OTC), encoded by the X chromosome gene Otc and involved in the urea cycle, may contribute as a congenital factor in hydronephrosis. This OTC dysfunction may be caused by genomic mutations in X chromosome genes contiguous to Otc, such as Tspan7, or via the genomic manipulations used to generate transgenic mice, including the introduction of Cre recombinase DNA cassettes and cleavage of loxP by Cre recombinase. Therefore, caution should be exercised in interpreting the hydronephrosis phenotype observed in transgenic mice as solely a physiological function of the target gene.

Reduced risk of overt hepatic encephalopathy and death after transjugular intrahepatic portosystemic shunt in patients with hepatic venovenous communications

PurposeHepatic venovenous communications (HVVC) is detectable in more than one-third of cirrhotic patients, where portal hypertension (PHT) tends to present more severely. We aimed to explore the prognostic implications of HVVC in patients with sinusoidal PHT treated by transjugular intrahepatic portosystemic shunt (TIPS). MethodThe multicenter data of patients (2020–2022) undergoing balloon-occluded hepatic venography during TIPS were retrospectively analyzed. Pre-TIPS total bile acids (TBA) levels in portal, hepatic and peripheral veins were compared between groups. The primary endpoint was the development of overt hepatic encephalopathy (HE) within one year after TIPS. Results183 patients were eligible and classified by the presence (n = 69, 37.7 %) or absence (n = 114, 62.3 %) of HVVC. The agreement between wedged hepatic venous pressure and portal venous pressure was poor in HVVC group (intraclass correlation coefficients [ICC]: 0.141, difference: 13.4 mmHg, p < 0.001), but almost perfect in non-HVVC group (ICC: 0.877, difference: 0.4 mmHg, p = 0.152). At baseline, patients with HVVC had lower Model for end-stage liver disease scores (p < 0.001), blood ammonia levels (p < 0.001), TBA concentrations in the hepatic (p = 0.011) and peripheral veins (p = 0.049) rather than in the portal veins (p = 0.516), and a higher portosystemic pressure gradient (p = 0.035), suggesting more effective intrahepatic perfusion in this group. Within 1-year post-TIPS, HVVC group had a lower incidence of overt HE (11.7 % vs. 30.5 %, p = 0.004, HR: 0.34, 95 % CI: 0.16–0.74, absolute risk difference [ARD]: −17.4) and an improved liver transplantation-free survival rate (97.1 % vs. 86.8 %, p = 0.021, HR: 0.16, 95 % CI: 0.05–0.91, ARD: −10.3). ConclusionsFor patients with sinusoidal PHT treated by TIPS, the presence of HVVC was associated with a reduced risk of overt HE and a potential survival benefit.

Влияние внутрижелудочного введения гидрокарбоната натрия или соляной кислоты на кишечную эндотоксемию у крыс при миелоабляции циклофосфамидом

Toxic effects of the myeloablative cyclophosphamide (CP) doses include damage to the gastrointestinal tract. This is manifested by gastrointestinal stasis, cytostatic drug-induced damage to the small intestinal mucosa, and acute gut-derived endotoxemia. The study was aimed to identify causal relationships between gastrointestinal stasis, enterocytopenia, and acute gut-derived endotoxemia in the rat model of the CP myeloablative conditioning. We assessed the effects of the intragastrically administered 0.48 М sodium bicarbonate (NaHCO3) solution or the 0.1 М hydrochloric acid (HCl) solution on the indicators of gastrointestinal stasis, enterocytopenia, portal blood levels of endotoxin, ammonia, urea, and urinary indican excretion. The stomach overfilled with chyme, decreased alkaline phosphatase and cholinesterase activity in the small intestinal tissues, 4.4-fold increased endotoxin levels, 4.6-fold increased urea levels, twofold increased portal blood plasma creatinine levels, and twofold increased urinary indican excretion were observed three days after intravenous administration of CP in a dose of 390 mg/kg. Intragastric administration of NaHCO3 or HCl partially prevented gastric stasis, but not acute gut-derived endotoxemia. Administration of NaHCO3, not HCl, prevented enterocytopenia in the duodenum. Acute gut-derived endotoxemia resulted mainly from the more intense release of the cecal microflora waste products into blood. Testing the use of sodium bicarbonate intragastric administration combined with the enteral detoxification and/or options for suppression of colonic microflora vegetation for prevention of the myeloablative cytostatic therapy complications is promising.

Treatment of ornithine transcarbamylase deficiency in a child with glyceryl phenylbutyrate

Glyceryl phenylbutyrate (GPB) serves as a long-term management medication for Ornithine transcarbamylase deficiency (OTCD), effectively controlling hyperammonemia, but there is a lack of experience in using this medicine in China. This article retrospectively analyzes the case of a child diagnosed with OTCD at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, including a review of related literature. After diagnosis, the patient was treated with GPB, followed by efficacy follow-up and pharmacological monitoring. The 6-year and 6-month-old male patient exhibited poor speech development, disobedience, temper tantrums, and aggressive behavior. Blood ammonia levels peaked at 327 μmol/L; urine organic acid analysis indicated elevated uracil levels; cranial MRI showed extensive abnormal signals in both cerebral hemispheres. Genetic testing revealed de novo mutation in the OTC gene (c.241T>C, p.S81P). Blood ammonia levels were approximately 43, 80, and 56 μmol/L at 1, 2, and 3 months after starting GPB treatment, respectively. During treatment, blood ammonia was well-controlled without drug-related adverse effects. The patient showed improvement in developmental delays, obedience, temperament, and absence of aggressive behavior.