Corrigendum:Disentangling brain PrPC proteoforms and their roles in physiology and disease

In the article titled“Disentangling brain PrPC proteoforms and their roles in physiology and disease”,published on pages 963-965,Issue 5,Volume 19 of Neural Regeneration Research(Vanni and Romolo,2024;doi:10.4103/1673-5374.385302),the name of the second author appears incorrectly.The correct name is Romolo Nonno.

COVID-19 and liver injury:Pathophysiology,risk factors,outcome and management in special populations

The coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus-2 is an ongoing health concern.In addition to affecting the respiratory system,COVID-19 can potentially damage other systems in the body,leading to extra-pulmonary manifestations.Hepatic manifestations are among the common consequences of COVID-19.Although the precise mechanism of liver injury is still questionable,several mechanisms have been hypothesized,including direct viral effect,cytokine storm,hypoxic-ischemic injury,hypoxiareperfusion injury,ferroptosis,and hepatotoxic medications.Risk factors of COVID-19-induced liver injury include severe COVID-19 infection,male gender,advanced age,obesity,and underlying diseases.The presentations of liver involvement comprise abnormalities in liver enzymes and radiologic findings,which can be utilized to predict the prognosis.Increased gamma-glutamyltransferase,aspartate aminotransferase,and alanine aminotransferase levels with hypoalbuminemia can indicate severe liver injury and anticipate the need for intensive care units’hospitalization.In imaging,a lower liver-to-spleen ratio and liver computed tomography attenuation may indicate a more severe illness.Furthermore,chronic liver disease patients are at a higher risk for severe disease and death from COVID-19.Nonalcoholic fatty liver disease had the highest risk of advanced COVID-19 disease and death,followed by metabolic-associated fatty liver disease and cirrhosis.In addition to COVID-19-induced liver injury,the pandemic has also altered the epidemiology and pattern of some hepatic diseases,such as alcoholic liver disease and hepatitis B.Therefore,it warrants special vigilance and awareness by healthcare professionals to screen and treat COVID-19-associated liver injury accordingly.

Physiology of medicinal and aromatic plants under drought stress

Drought poses a significant challenge,restricting the productivity of medicinal and aromatic plants.The strain induced by drought can impede vital processes like respiration and photosynthesis,affecting various aspects of plants’growth and metabolism.In response to this adversity,medicinal plants employ mechanisms such as morphological and structural adjustments,modulation of drought-resistant genes,and augmented synthesis of secondary metabolites and osmotic regulatory substances to alleviate the stress.Extreme water scarcity can lead to leaf wilting and may ultimately result in plant death.The cultivation and management of medicinal plants under stress conditions often differ from those of other crops.This is because the main goal with medicinal plants is not only to increase the yield of the above-ground parts but also to enhance the production of active ingredients such as essential oils.To elucidate these mechanisms of drought resistance in medicinal and aromatic plants,the current review provides a summary of recent literature encompassing studies on the morphology,physiology,and biochemistry of medicinal and aromatic plants under drought conditions.

Frailty in end-stage liver disease:Understanding pathophysiology,tools for assessment,and strategies for management

Frailty and sarcopenia are frequently observed in patients with end-stage liver disease.Frailty is a complex condition that arises from deteriorations across various physiological systems,including the musculoskeletal,cardiovascular,and immune systems,resulting in a reduced ability of the body to withstand stressors.This condition is associated with declined resilience and increased vulnerability to negative outcomes,including disability,hospitalization,and mortality.In cirrhotic patients,frailty is influenced by multiple factors,such as hyperammonemia,hormonal imbalance,malnutrition,ascites,hepatic encephalopathy,and alcohol intake.Assessing frailty is crucial in predicting morbidity and mortality in cirrhotic patients.It can aid in making critical decisions regarding patients’eligibility for critical care and transplantation.This,in turn,can guide the development of an individualized treatment plan for each patient with cirrhosis,with a focus on prioritizing exercise,proper nutrition,and appropriate treatment of hepatic complications as the primary lines of treatment.In this review,we aim to explore the topic of frailty in liver diseases,with a particular emphasis on pathophysiology,clinical assessment,and discuss strategies for preventing frailty through effective treatment of hepatic complications.Furthermore,we explore novel assessment and management strategies that have emerged in recent years,including the use of wearable technology and telemedicine.

Effects of Inoculation with Phosphate Solubilizing Bacteria on the Physiology,Biochemistry,and Expression of Genes Related to the Protective Enzyme System of Fritillaria taipaiensis P.Y.Li

Fritillaria taipaiensis P.Y.Li is a widely used medicinal herb in treating pulmonary diseases.In recent years,its wild resources have become scarce,and the demand for efficient artificial cultivation has significantly increased.This article is the first to apply phosphate solubilizing bacteria isolated from the rhizosphere soil of F.taipaiensis P.Y.Li to the cultivation process of F.taipaiensis P.Y.Li.The aim is to identify suitable reference strains for the artificial cultivation and industrial development of F.taipaiensis P.Y.Li by examining the effects of various phosphate solubilizing bacteria and their combinations on photosynthesis,physiological and biochemical properties,and gene expression related to the protective enzyme system in F.taipaiensis P.Y.Li.The experiment,conducted in pots at room temperature,included a control group(CK)and groups inoculated with inorganic phosphorussolubilizing bacteria:W1(Bacillus cereus),W2(Serratia plymuthica),W12(Bacillus cereus and Serratia plymuthica),and groups inoculated with organophosphorus-solubilizing bacteria:Y1(Bacillus cereus),Y2(Bacillus cereus),Y12(Bacillus cereus and Bacillus cereus),totaling seven groups.Compared to CK,most growth indices in the bacterial addition groups showed significant differences,with W12 achieving the highest values in all indices except the leaf area index.The content of photosynthetic pigments,photosynthetic parameters,and osmoregulatory substances increased variably in each bacterial treatment group.W12 exhibited the highest content of chlorophyll a and soluble protein,while W1 had the highest free proline content.The activities of peroxidase(POD),superoxide dismutase(SOD),and catalase(CAT)in all inoculated groups were higher than in CK,with significant changes in SOD and CAT activities.The malondialdehyde(MDA)content in all inoculated groups was lower than in CK,with Y12 being the lowest,at approximately 30%of CK.Gene expression corresponding to these three enzymes also increased variably,with POD expression in Y2 being the highest at 2.73 times that of CK.SOD and CAT expression in Y12 were the highest,at 1.84 and 4.39 times that of CK,respectively.These results indicate that inoculating phosphate solubilizing bacteria can enhance the growth of F.taipaiensis P.Y.Li,with the mixed inoculation groups W12 and Y12 demonstrating superior effects.This lays a theoretical foundation for selecting bacterial fertilizers in the cultivation process of F.taipaiensis P.Y.Li.

Liver physiology and liver diseases in the elderly

The liver experiences various changes with aging that could affect clinical characteristics and outcomes in patients with liver diseases.Both liver volume and blood flow decrease significantly with age.These changes and decreased cytochrome P450 activity can affect drug metabolism,increasing susceptibility to drug-induced liver injury.Immune responses against pathogens or neoplastic cells are lower in the elderly,although these individuals may be predisposed to autoimmunity through impairment of dendritic cell maturation and reduction of regulatory T cells.These changes in immune functions could alter the pathogenesis of viral hepatitis and autoimmune liver diseases,as well as the development of hepatocellular carcinoma.Moreover,elderly patients have significantly decreased reserve functions of various organs,reducing their tolerability to treatments for liver diseases.Collectively,aged patients show various changes of the liver and other organs that could affect the clinical characteristics and management of liver diseases in these patients.

Effects of Different Arbuscular Mycorrhizal Fungi on Physiology of Viola prionantha under Salt Stress

Arbuscular mycorrhizal(AM)fungi distribute widely in natural habits and play a variety of ecological functions.In order to test the physiological response to salt stress mediated by different AM fungi,Viola prionantha was selected as the host,the dominant AM fungus in the rhizosphere of V.philippica growing in Songnen saline-alkali grassland,Rhizophagus irregularis,and their mixtures were used as inoculants,and NaCl stress was applied after the roots were colonized.The results showed that V.philippica could be colonized by AM fungi in the field and the colonization rate ranged from 73.33%to 96.67%,and Claroideoglomus etunicatum was identified as the dominant AM fungi species in the rhizosphere of V.philippica by morphology combined with sequencing for AM fungal AML1/AML2 target.Inoculation with both the species resulted in the formation of mycorrhizal symbiosis(the colonization rate was more than 70%)and AM fungi significantly enhanced plants’tolerance to salt stress of varying magnitude.Higher activity of antioxidant enzymes and augmented levels of proline and other osmoregulators were observed in AM plants.The content of MDA in CK was higher than that in the inoculations with the stress of 100,200,and 250 mM.All indices except soluble protein content and MDA content were significantly correlated with AM fungal colonization indices.The analysis for different AM fungal effects showed that the mixtures and R.irregularis worked even better than C.etunicatum.These results will provide theoretical support for the exploration and screening of salt-tolerant AM fungi species and also for the application of AM-ornamental plants in saline-alkali urban greening.

Effects of Flooding Stress on Growth and Root Physiology and Biochemistry of Grafted Red-seed Watermelon Seedlings

[Objectives]This study was conducted to explore how to improve the waterlogging tolerance of red-seed watermelon through grafting,to provide a theoretical basis for its cultivation in rainy season.[Methods]The effects of flooding stress on the growth and root physiological and biochemical characteristics of grafted and own-rooted red-seed watermelon seedlings were studied using Luffa as rootstocks and"Zhongxin 1"red-seed watermelon as scions.[Results]After flooding stress,the biomass and root activity of grafted seedlings of red-seed watermelon were significantly higher than those of own-rooted seedlings.With the prolongation of flooding stress time,the soluble sugar and proline content showed a trend of first increasing and then decreasing,and the grafted seedlings had a larger increase and a smaller decrease,and were always significantly higher than own-rooted seedlings in the same period.The content of malondialdehyde in the root system of grafted seedlings increased first and then decreased,while it continued to increase in own-rooted seedlings,and the increase in own-rooted seedlings was significantly greater than that in grafted seedlings during the same period.[Conclusions]Grafting on Luffa rootstocks could improve waterlogging tolerance of red-seed watermelon.

Post reperfusion syndrome during liver transplantation:From pathophysiology to therapy and preventive strategies

This review aims at evaluating the existing evidence regarding post reperfusion syndrome, providing a description of the pathophysiologic mechanisms involved and possible management and preventive strategies. A Pub Med search was conducted using the Me SH database, "Reperfusion" AND "liver transplantation" were the combined Me SH headings; EMBASE and the Cochrane library were also searched using the same terms. 52 relevant studies and one ongoing trial were found. The concept of post reperfusion syndrome has evolved through years to a multisystemic disorder. The implications of the main organ, recipient and procedure related factors in the genesis of this complex syndrome are discussed in the text as the novel pharmacologic and technical approaches to reduce its incidence. However the available evidence about risk factors, physiopathology and preventive measures is still confusing, the presence of two main definitions and the numerosity of possible confounding factors greatly complicates the interpretation of the studies.

Role of autophagy in the pathophysiology of nonalcoholic fatty liver disease:A controversial issue

Autophagy is a mechanism involved in cellular homeostasis under basal and stressed conditions delivering cytoplasmic content to the lysosomes for degradation to macronutrients.The potential role of autophagy in disease is increasingly recognised and investigated in the last decade.Nowadays it is commonly accepted that autophagy plays a role in the hepatic lipid metabolism.Hence,dysfunction of autophagy may be an underlying cause of non-alcoholic fatty liver disease.However,controversy of the exact role of autophagy in the lipid metabolism exists:some publications report a lipolytic function of autophagy,whereas others claim a lipogenic function.This review aims to give an update of the present knowledge on autophagy in the hepatic lipid metabolism,hepatic insulin resistance,steatohepatitis and hepatic fibrogenesis.

Functional CT for assessment of early vascular physiology in liver tumors

BACKGROUND: CT perfusion has been reported to have great advantages in detecting hepatic diseases. However, currently there are no studies showing the potential value of multi-slice CT perfusion with the deconvolution model method in diagnosing early hemodynamic changes caused by liver tumors. This study was undertaken to determine if early hemodynamic changes caused by liver tumors can be depicted with the perfusion imaging of multi-slice CT. METHODS: Ten New Zealand white rabbits before and after VX2 liver tumor inoculation served as the experimental animals. Ten normal rabbits served as controls. All underwent multi-slice CT perfusion for the measurement of hepatic blood flow (HBF), hepatic blood volume (HBV), mean transit time (MTT), permeability of capillary vessel surface (PS) and hepatic artery index (HAI). RESULTS: With the exception of MTT, which decreased significantly at the tumor periphery, HBF, HBV,. PS and HAI increased significantly compared with the surrounding normal tissue. All these changes occurred at days 5-9 after tumor inoculation. Statistically significant changes in these values were detected with tumor growth. CONCLUSIONS: The hemodynamic changes in the liver caused by rabbit VX2 liver tumor can be detected after tumor inoculation, and functional CT can evaluate the physiological characteristics of early tumor angiogenesis.

Pathophysiology, epidemiology, classification and treatment options for polycystic liver diseases

Polycystic liver diseases(PLD)represent a group of genetic disorders in which cysts occur in the liver(autosomal dominant polycystic liver disease)or in combination with cysts in the kidneys(autosomal dominant polycystic kidney disease).Regardless of the genetic mutations,the natural history of these disorders is alike.The natural history of PLD is characterized by a continuous increase in the volume and the number of cysts.Both genders are affected;however,women have a higher prevalence.Most patients with PLD are asymptomatic and can be managed conservatively.Severe symptoms can affect 20%of patients who develop massive hepatomegaly with compression of the surrounding organs.Rrarely,patients with PLD suffer from acutecomplications caused by the torsion of hepatic cysts,intraluminal cystic hemorrhage and infections.The most common methods for the diagnosis of PLD are cross sectional imaging studies.Abdominal ultrasound and computerized tomography are the two most frequently used investigations.Magnetic resonance imaging is more sensitive and specific,and it is a valuable test for patients with intravenous contrast allergies or renal dysfunction.Different treatment modalities are available to physicians caring for these patients.Medical treatment has been ineffective.Percutaneous sclerotherapy,transarterial embolization,cyst fenestration,hepatic resection and liver transplantation are indicated to specific groups of patients and have to be tailored according to the extent of disease.This review outlines the current knowledge of the pathophysiology,clinical course,diagnosis and treatment strategies of PLD.

Dissecting the molecular pathophysiology of drug-induced liver injury

Drug-induced liver injury(DILI) has become a major topic in the field of Hepatology and Gastroenterology. DILI can be clinically divided into three phenotypes: hepatocytic, cholestatic and mixed. Although the clinical manifestations of DILI are variable and the pathogenesis complicated, recent insights using improved preclinical models, have allowed a better understanding of the mechanisms that trigger liver damage. In this review, we will discuss the pathophysiological mechanisms underlying DILI. The toxicity of the drug eventually induces hepatocellular damage through multiple molecular pathways, including direct hepatic toxicity and innate and adaptive immune responses. Drugs or their metabolites, such as the common analgesic, acetaminophen, can cause direct hepatic toxicity through accumulation of reactive oxygen species and mitochondrial dysfunction. The innate and adaptive immune responses play also a very important role in the occurrence of idiosyncratic DILI. Furthermore, we examine common forms of hepatocyte death and their association with the activation of specific signaling pathways.

Hemostasis in liver transplantation:Pathophysiology,monitoring,and treatment

Recent findings in the pathophysiology and monitoring of hemostasis in patients with end stage liver disease have major impact on coagulation management during liver transplantation. There is increasing evidence, that the changes in both coagulation factors and platelet count regularly observed in patients with liver cirrhosis cannot be interpreted as a reliable indicator of diffuse bleeding risk. Instead, a differentiated view on hemostasis has led to the concept of a rebalanced coagulation system: While it is important to recognize that procoagulant factors are reduced in liver cirrhosis, it is also evident that synthesis of anticoagulant factors and fibrinolytic proteins produced in the liver is also diminished. Similarly, the decreased platelet count may be counterbalanced by increased platelet aggregability caused by highly active von Willebrand multimeres. The coagulation system is therefor stated to be rebalanced. While under normal "unstressed" conditions diffuse bleeding is rarely observed, however both diffuse bleeding or thrombus formation may occur when compensation mechanisms are exhausted. While most patients presenting for liver transplantation have severe cirrhosis, liver function and thus production of pro- and anticoagulant factors can be preserved especially in cholestatic liver disease. During liver transplantation, profound changes in the hemostasis system can occur. Surgical bleeding can lead to diffuse bleeding as coagulation factors and platelets are already reduced. Ischemia and tissue trauma can lead to alterations of hemostasis comparable to trauma induced coagulopathy. A further common disturbance often starting with the reperfusion of the transplanted organ is hyperfibrinolysis which can eventually precipitate complete consumption of fibrinogen and an endogenous heparinization by glycocalyx shedding. Moreover, thrombotic events inliver transplantations are not uncommon and contribute to increased mortality. Besides conventional laboratory methods, bed-side monitoring of hemostasis(e.g., thrombelastography, thrombelastometry) is often used during liver transplantation to rapidly diagnose decreases in fibrinogen and platelet count as well as hyperfibrinolysis and to guide treatment with blood products, factor concentrates, and antifibrinolytics. There is also evidence which suggests when algorithms based on bed-side hemostasis monitoring are used a reduction of blood loss, blood product use, and eventual mortality are possible. Notably, the bed-side monitoring of anticoagulant pathways and the thrombotic risk is not possible at time and thus a cautious and restrictive use of blood products is recommended.

Differing responses of root morphology and physiology to nitrogen application rates and their relationships with grain yield in rice

Root morphology and physiology influence aboveground growth and yield formation in rice.However,root morphological and physiological differences among rice varieties with differing nitrogen(N)sensitivities and their relationship with grain yield are still unclear.In this study,rice varieties differing in N sensitivity over many years of experiments were used.A field experiment with multiple N rates(0,90,180,270,and 360 kg ha^(-1))was conducted to elucidate the effects of N application on root morphology,root physiology,and grain yield.A pot experiment with root excision and exogenous application of 6-benzyladenine(6-BA)at heading stage was used to further verify the above effects.The findings revealed that(1)under the same N application rate,N-insensitive varieties(NIV)had relatively large root biomass(root dry weight,length,and number).Grain yield was associated with root biomass in NIV.The oxidation activity and zeatin(Z)+zeatin riboside(ZR)contents in roots obviously and positively correlated with grain yield in N-sensitive varieties(NSV),and accounted for its higher grain yield than that of NIV at lower N application rates(90 and 180 kg ha^(-1)).(2)The root dry weight required for equal grain yield of NIV was greater than that of NSV.Excision of 1/10 and 1/8 of roots at heading stage had no discernible effect on the yield of Liangyoupeijiu(NIV),and it significantly reduced yield by 11.5%and 21.3%in Tianyouhuazhan(NSV),respectively,compared to the treatment without root excision.The decrease of filled kernels and grain weight after root excision was the primary cause for the yield reduction.Root excision and exogenous 6-BA application after root excision had little influence on the root activity of NIV.The oxidation activity and Z+ZR contents in roots of NSV decreased under root excision,and the increase in the proportion of excised roots aggravated these effects.The application of exogenous 6-BA increased the root activity of NSV and increased filled kernels and grain weight,thereby reducing yield loss after root excision.Thus,the root biomass of NIV was large,and there may be a phenomenon of"root growth redundancy."Vigorous root activity was an essential feature of NSV.Selecting rice varieties with high root activity or increasing root activity by cultivation measures could lead to higher grain yield under lower N application rates.

Ex vivo liver resection and auto-transplantation as an alternative for the treatment of liver malignancies: Progress and challenges

Hepatectomy is still the major curative treatment for patients with liver malignancies.However,it is still a big challenge to remove the tumors in the central posterior area,especially if their location involves the retrohepatic inferior vena cava and hepatic veins.Ex vivo liver resection and auto-transplantation(ELRA),a hybrid technique of the traditional liver resection and transplantation,has brought new hope to these patients and therefore becomes a valid alternative to liver transplantation.Due to its technical difficulty,ELRA is still concentrated in a few hepatobiliary centers that have experienced surgeons in both liver resection and liver transplantation.The efficacy and safety of this technique has already been demonstrated in the treatment of benign liver diseases,especially in the advanced alveolar echinococcosis.Recently,the application of ELRA for liver malignances has gained more attention.However,standardization of clinical practice norms and international consensus are still lacking.The prognostic impact in these oncologic patients also needs further evaluation.In this review,we summarized the principles and recent progresses on ELRA.

Role of autophagy in liver physiology and pathophysiology

Autophagy is a highly conserved intracellular degradation pathway by which bulk cytoplasm and superfluous or damaged organelles are enveloped by double membrane structures termed autophagosomes. The autophago-somes then fuse with lysosomes for degradation of their contents, and the resulting amino acids can then recycle back to the cytosol. Autophagy is normally activated in response to nutrient deprivation and other stressors and occurs in all eukaryotes. In addition to maintaining energy and nutrient balance in the liver, it is now clear that autophagy plays a role in liver protein aggregates related diseases, hepatocyte cell death, steatohepatitis, hepatitis virus infection and hepatocellular carcinoma. In this review, I discuss the recent findings of autophagy with a focus on its role in liver pathophysiology.

Boxing Practitioners Physiology Review: 2. Systemic Responses and Adaptations

The present journal paper is the second of the three parts of a whole boxing practitioners physiology review. It is related to the boxing practice-derived systemic responses and adaptations. The first part of the review has dealt with kinanthropometric parameters, skeletal muscle recruitment and ergometry. The following and third part of the review is going to deal with dietary supplementation, weight control, recovery, altitude, faith, life expectancy, gender and childhood. Search engines and printed documents have helped gather the information that have been commented in the present and second part: responses and/or adaptations relating to 1) metabolism, 2) skeleton, 3) nervous system, 4) endocrine system, 5) cardiovascular system, 6) urinary tract and 7) pulmonary system. Detailed titles and subtitles of this part of the review are found at the end of the journal paper introduction. The main teachings from the present journal paper may be acquired through the consultation of the tables and figures that are positioned in the text, not forgetting the reminders and advice(s) that appear at the end of each of the seven parts of the journal paper (2.1.6., 2.2.2., 2.3.2., 2.4.2., 2.5.4, 2.6.4. and 2.7.3.).

Small-for-size syndrome in liver transplantation:Definition,pathophysiology and management

Background:Since the first success in an adult patient,living donor liver transplantation(LDLT)has become an universally used procedure.Small-for-size syndrome(SFSS)is a well-known complication after partial LT,especially in cases of adult-to-adult LDLT.The definition of SFSS slightly varies among transplant physicians.The use of a partial liver graft has risks of SFSS development.Persistent portal vein(PV)hypertension and PV hyper-perfusion after LT were identified as the main factors.Hence,various approaches were explored to modulate PV flow and decrease PV pressure in order to alleviate this syndrome.Herein,the definition,clinical symptoms,pathophysiology,basic research,as well as preventive and treatment strategies for SFSS are reviewed based on an extensive review of the literature and on our own experiences.Data sources:The articles were collected through PubMed using search terms“liver transplantation”,“living donor liver transplantation”,“living liver donation”,“partial graft”,“small-for-size graft”,“small-forsize syndrome”,“graft volume”,“remnant liver”,“standard liver volume”,“graft to recipient body weight ratio”,“sarcopenia”,“porcine”,“swine”,and“rat”.English publications published before March 31,2020 were included in this review.Results:Many transplant surgeons performed PV flow modulation,including portocaval shunt,splenic artery ligation and splenectomy.With these techniques,patient outcome has been improved even when using a"small"graft.Other factors,such as preoperative recipients’nutritional and skeletal muscle status,graft congestion,and donor factors,were also identified as risk factors which all have been addressed using various strategies.Conclusions:The surgical approach controlling PV flow and pressure could help to prevent SFSS especially in severely ill recipients.In the absence of efficacious medications to resolve SFSS,conservative treatments,including aggressive fluid balance correction for massive ascites,anti-microbiological therapy to prevent or control sepsis and intensive nutritional therapy,are all required if SFSS could not be prevented.

Pathophysiology of cerebral oedema in acute liver failure

Cerebral oedema is a devastating consequence of acute liver failure(ALF)and may be associated with the development of intracranial hypertension and death.In ALF,some patients may develop cerebral oedema and increased intracranial pressure but progression to lifethreatening intracranial hypertension is less frequent than previously described,complicating less than one third of cases who have proceeded to coma since the advent of improved clinical care.The rapid onset of encephalopathy may be dramatic with the development of asterixis,delirium,seizures and coma.Cytotoxic and vasogenic oedema mechanisms have been implicated with a preponderance of experimental data favouring a cytotoxic mechanism.Astrocyte swelling is the most consistent neuropathological finding in humans with ALF and ammonia plays a definitive role in the development of cytotoxic brain oedema.The mechanism(s)by which ammonia induces astrocyte swelling remains unclear but glutamine accumulation within astrocytes has led to the osmolyte hypothesis.Current evidence also supports an alternate‘Trojan horse’hypothesis,with glutamine as a carrier of ammonia into mitochondria,where its accumulation results in oxidative stress,energy failure and ultimately astrocyte swelling.Although a complete breakdown of the blood-brain barrier is not evident in human ALF,increased permeation to water and other small molecules such as ammonia has been demonstrated resulting from subtle alterations in the protein composition of paracellular tight junctions.At present,there is no fully efficacious therapy for cerebral oedema other than liver transplantation and this reflects our incomplete knowledge of the precise mechanisms underlying this process which remain largely unknown.