Acute Liver Research Articles

Severe septic complications of acute fatty liver of pregnancy: case series in Assiut University women's health hospital

Severe septic complications of acute fatty liver of pregnancy: case series in Assiut University women's health hospital

Hedgehog signalling in liver regeneration

Regeneration of adult livers requires Hh-dependent modulation of epithelial-mesenchymal transitions in multipotent progenitors. Data generated by studying models of acute and chronic liver injury reveal that robust epithelial to mesenchymal transitions (EMT) normally occur in injured livers, and show that conditionally abrogating canonical Hedgehog signaling in multi-potent aSMA-expressing cells blocks these EMT, instead triggering a cascade of mesenchymal-to-epithelial transitions (MET). This has global consequences for liver wound healing. Regeneration of different types of liver cells becomes unbalanced, leading to excessive accumulation of quiescent HSC but reduced outgrowth of hepatocytic and ductular progenitors and their progeny, as well as depletion of MF populations. Thus, de-regulating Hh-sensitive EMT/MET responses disrupts both scarring and regeneration of injured livers. These findings, in turn, suggest that the liver is uniquely suited for regeneration because it harbors large populations of multi-potent progenitors and is generally able to constrain signals, such as Hedgehog, that modulate the differentiation of these cells towards less epithelial (and more mesenchymal) phenotypes.

Early-onset diabetes mellitus and neurodevelopmental retardation: the first Greek case of Wolcott-Rallison syndrome

Wolcott-Rallison syndrome (WRS) is a very rare genetic disorder, which is transmitted by autosomal recessive inheritance and results from mutations in the gene encoding the eukaryotic initiation factor 2-α kinase-3 (EIF2AK3). The cardinal features of the syndrome include early-onset insulin-dependent diabetes mellitus, multiple epiphyseal dysplasia, and growth retardation. We present the case of a 13-year-old Greek boy with a known history of infancy-onset diabetes mellitus and was found to have WRS at the age of 4 years. He presented with acute liver and renal insufficiency in addition to skeletal dysplasia and neurodevelopmental retardation. The clinical suspicion of WRS was confirmed by molecular analysis of the EIF2AK3 gene. The patient was found to be a compound heterozygote with two different novel mutations (c.2776C>T, p.R902X and c.3038A>G, p.Y989C). The current patient is one of the longer survivors.

Acute abdomen due appendicitis with atypical presentation leading to shock in an obese patient and with chronic liver disease

AIMS: To expose a case of acute abdomen due to appendicitis whose diagnosis was difficult and complicated because of the patient's profile and his comorbidities.
 
 CASE DESCRIPTION: Male patient, 52 years old, superobese, smoker and with chronic liver disease, complaining of acute abdominal pain in the right hypochondrium, vomiting and low diuresis. Initially with no signs of peritoneal irritation, the patient was medically managed, but presented worsening of clinical status, progressing to shock and cardiac arrest. The investigation by laparotomy found acute appendicitis, collateral circulation and liver cirrhosis.
 
 CONCLUSIONS: Acute abdomen has great impact on emergency care and, since it comprises several clinical situations, knowing and suspecting its main causes and its atypical presentations becomes essential, mainly in cases of difficult diagnosis.

Sa1317 Does Race Impact HCV Knowledge Among Oklahomans?

Background and aims: Peginterferon (Peg-IFN) alpha in combination with ribavirin (RBV) represents the current optimal therapy for chronic hepatitis C (CHC). Interstitial pneumonitis is a rare but rapidly progressing and potentially fatal adverse event that has been described. The review includes an illustrative patient to clarify diagnosis and educate treating team on management strategies. Methodology: A systematic literature search reporting patients with interstitial pneumonitis who had radiological confirmation, and if possible histological confirmation of the condition. Patients who had undergone interferon-based therapy, either as a standalone therapy or in combination with ribavirin, were included. The indication for the use of Interferon-based therapy was for Hepatitis C only.Results: 33 cases of Interferonrelated interstitial pneumonitis were found, including the patient in the present review. The median age at presentation of 56.1 years (range 39-72 years) with no gender preponderance with 17 males (51.5%) and 16 females (48.5%). There appears to be a significant proportion of affected patients having been on Interferon-alpha-2b which was prescribed in 57.5% of patient (19 patients). On review of the published cases, the mortality rate is 12% with 4 deceased patients. All these patients were treated with Interferon-alpha-2b. The causes of death were multisystem organ failure, chronic hypoxia-induced cerebral oedema, acute cholestatic hepatitis and liver failure and as with our patient, hypoxic respiratory failure. HRCT is the radiological investigation of choice for suspected interstitial pneumonitis, with bronchoalveolar lavage (BAL) findings being not specific. HRCT often shows ground-glass opacities that may be patchy or diffuse, with upper lobe-predominant centrilobular illdefined nodules. Bronchioalveolar lavage findings include lymphocytosis >50%, a low CD4 to CD8 ratio, and occasionally, an increase in neutrophils. In all the reported cases, the culprit drug was ceased. Majority (nineteen patients) were commenced on steroid therapy. All four deaths occurred during or after treatment with intravenous steroids. In one of the patients with relapsed disease, Azathioprine was added. Conclusion: Interstitial pneumonitis is a rare, but life-threatening side effect that should be considered in the differential diagnosis of patients presenting with respiratory symptoms during or after Interferon-based therapy. There is lack of data to guide treatment and current practice is to cease the said drug and commence high dose steroids, either in oral or intravenous form. Pre-treatment respiratory function tests and CT scan with mid-treatment follow-up shoule be considered in all patients on treatment and the early withdrawal of treatment is advocated in patients with rapid clinical decline.

Sa1316 Interferon Induced Interstitial Pneumonitis: A Systematic Review Including an Illustrative Patient

Background and aims: Peginterferon (Peg-IFN) alpha in combination with ribavirin (RBV) represents the current optimal therapy for chronic hepatitis C (CHC). Interstitial pneumonitis is a rare but rapidly progressing and potentially fatal adverse event that has been described. The review includes an illustrative patient to clarify diagnosis and educate treating team on management strategies. Methodology: A systematic literature search reporting patients with interstitial pneumonitis who had radiological confirmation, and if possible histological confirmation of the condition. Patients who had undergone interferon-based therapy, either as a standalone therapy or in combination with ribavirin, were included. The indication for the use of Interferon-based therapy was for Hepatitis C only.Results: 33 cases of Interferonrelated interstitial pneumonitis were found, including the patient in the present review. The median age at presentation of 56.1 years (range 39-72 years) with no gender preponderance with 17 males (51.5%) and 16 females (48.5%). There appears to be a significant proportion of affected patients having been on Interferon-alpha-2b which was prescribed in 57.5% of patient (19 patients). On review of the published cases, the mortality rate is 12% with 4 deceased patients. All these patients were treated with Interferon-alpha-2b. The causes of death were multisystem organ failure, chronic hypoxia-induced cerebral oedema, acute cholestatic hepatitis and liver failure and as with our patient, hypoxic respiratory failure. HRCT is the radiological investigation of choice for suspected interstitial pneumonitis, with bronchoalveolar lavage (BAL) findings being not specific. HRCT often shows ground-glass opacities that may be patchy or diffuse, with upper lobe-predominant centrilobular illdefined nodules. Bronchioalveolar lavage findings include lymphocytosis >50%, a low CD4 to CD8 ratio, and occasionally, an increase in neutrophils. In all the reported cases, the culprit drug was ceased. Majority (nineteen patients) were commenced on steroid therapy. All four deaths occurred during or after treatment with intravenous steroids. In one of the patients with relapsed disease, Azathioprine was added. Conclusion: Interstitial pneumonitis is a rare, but life-threatening side effect that should be considered in the differential diagnosis of patients presenting with respiratory symptoms during or after Interferon-based therapy. There is lack of data to guide treatment and current practice is to cease the said drug and commence high dose steroids, either in oral or intravenous form. Pre-treatment respiratory function tests and CT scan with mid-treatment follow-up shoule be considered in all patients on treatment and the early withdrawal of treatment is advocated in patients with rapid clinical decline.

The comparison of DPPH-scavenging capacity and anti-inflammatory effects of phenolic compounds isolated from the stems of Stewartia koreana Nakai

The Stewartia koreana Nakai (SK) had been used in oriental traditional medicine as a remedy for acute gastroenteritis, liver diseases, quadriplegia and pain. The antioxidant activity guided isolation 80% methyl extract from stems of SK yielded eight phenolic compounds. We evaluated the anti-oxidative and anti-inflammatory effects of these compounds via assays of 1,1-diphenyl-2-picrylhydazyl (DPPH) radicals and inhibition of nitric oxide (NO) production in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. The results demonstrated that syringaresinol (6) exhibited significant DPPH radical-scavenging activity and inhibitory effects on NO production compared with its positive controls, ascorbic acid and l-NMMA, respectively.

Extracellular histones in tissue injury and inflammation

Neutrophil NETosis is an important element of host defense as it catapults chromatin out of the cell to trap bacteria, which then are killed, e.g., by the chromatin's histone component. Also, during sterile inflammation TNF-alpha and other mediators trigger NETosis, which elicits cytotoxic effects on host cells. The same mechanism should apply to other forms of regulated necrosis including pyroptosis, necroptosis, ferroptosis, and cyclophilin D-mediated regulated necrosis. Beyond these toxic effects, extracellular histones also trigger thrombus formation and innate immunity by activating Toll-like receptors and the NLRP3 inflammasome. Thereby, extracellular histones contribute to the microvascular complications of sepsis, major trauma, small vessel vasculitis as well as acute liver, kidney, brain, and lung injury. Finally, histones prevent the degradation of extracellular DNA, which promotes autoimmunization, anti-nuclear antibody formation, and autoimmunity in susceptible individuals. Here, we review the current evidence on the pathogenic role of extracellular histones in disease and discuss how to target extracellular histones to improve disease outcomes.

G472 Use of Continuous Venovenous haemofiltration (CVVH) in patients with congenital metabolic disorders – A recent single-centre experience

IntroductionCongenital metabolic disorders are a rare but important cause of critical illness in children. Continuous venovenous haemofiltration (CVVH) is instituted as life-saving therapy for severe hyperammonaemia, metabolic acidosis and encephalopathy...

Dual role of acetaminophen in promoting hepatoma cell apoptosis and kidney fibroblast proliferation

Acetaminophen (APAP), is a safe analgesic and antipyretic drug at therapeutic dose, and is widely used in the clinic. However, high doses of APAP can induce hepatotoxicity and nephrotoxicity. Most studies have focused on high-dose APAP-induced acute liver and kidney injury. So far, few studies have investigated the effects of the therapeutic dose (1/10 of the high dose) or of the low dose (1/100 of the high dose) of APAP on the cells. The aim of this study was to investigate the cellular effects of therapeutic- or low-dose APAP treatment on hepatoma cells and kidney fibroblasts. As expected, high-dose APAP treatment inhibited while therapeutic and low-dose treatment did not inhibit cell survival of kidney tubular epithelial cells. In addition, therapeutic-dose treatment induced an increase in the H2O2 level, activated the caspase-9/-3 cascade, and induced cell apoptosis of hepatoma cells. Notably, APAP promoted fibroblast proliferation, even at low doses. This study demonstrates that different cellular effects are exerted upon treatment with different APAP concentrations. Our results indicate that treatment with the therapeutic dose of APAP may exert an antitumor activity on hepatoma, while low-dose treatment may be harmful for patients with fibrosis, since it may cause proliferation of fibroblasts.

Lactate Reduces Liver and Pancreatic Injury in Toll-Like Receptor– and Inflammasome-Mediated Inflammation via GPR81-Mediated Suppression of Innate Immunity

The NACHT, LRR, and pyrin domain-containing protein 3 (NLRP3) inflammasome induces inflammation in response to organ injury, but little is known about its regulation. Toll-like receptors (TLRs) provide the first signal required for activation of the inflammasome and stimulate aerobic glycolysis to generate lactate. We examined whether lactate and the lactate receptor, Gi-protein-coupled receptor 81 (GPR81), regulate TLR induction of signal 1 and limit inflammasome activation and organ injury. Primary mouse macrophages and human monocytes were incubated with TLR4 agonists and lactate and assayed for levels of pro-interleukin (IL)1β, NLRP3, and caspase-1 (CASP1); release of IL1β; and activation of nuclear factor-κB (NF-κB) and caspase-1. Small interfering RNAs were used to reduce levels of GPR81 and arrestin β-2 (ARRB2), and an NF-κB luciferase reporter transgene was transfected in RAW 264.7 cells. Cell lysates were analyzed by immunoprecipitation with an antibody against GPR81. Acute hepatitis was induced in C56BL/6N mice by administration of lipopolysaccharide and D-galactosamine. Acute pancreatitis was induced by administration of lipopolysaccharide and cerulein. Some mice were given intraperitoneal injections of sodium lactate or small interfering RNA against Gpr81. Activation of NF-κB in tissue macrophages was assessed in mice that expressed a reporter transgene. In macrophages and monocytes, increasing concentrations of lactate reduced TLR4-mediated induction of Il1B, Nlrp3, and Casp1; activation of NF-κB; release of IL1β; and cleavage of CASP1. GPR81 and ARRB2 physically interacted and were required for these effects. The administration of lactate reduced inflammation and organ injury in mice with immune hepatitis; this reduction required Gpr81 dependence invivo. Lactate also prevented activation of NF-κB in macrophages of mice, and, when given after injury, reduced the severity of acute pancreatitis and acute liver injury. Lactate negatively regulates TLR induction of the NLRP3 inflammasome and production of IL1β, via ARRB2 and GPR81. Lactate could be a promising immunomodulatory therapy for patients with acute organ injury.

Index of Suspicion in the Nursery

A female preterm infant was born at 28-weeks’ gestation to a G3P2A1 mother (third degree consanguineous marriage) by emergency cesarean delivery due to severe fetal growth restriction, oligohydramnios, and increasing liver transaminase levels in the mother. First conception was miscarriage at 12-weeks’ gestation. The second conception was intrauterine fetal demise at 30-weeks’ gestation; the pregnancy was complicated with acute fatty liver of pregnancy (AFLP) and acute kidney injury. Placenta showed massive perivillous fibrin deposition. Present pregnancy was spontaneously conceived. Pre-pregnancy, mother was diagnosed as hypothyroid and was started on thyroxine. She had also been started on aspirin since the last pregnancy and had received a complete course of antenatal steroids at 27-weeks’ gestation. Blood pressure of the mother at the time of admission was 140/90 mm Hg. This pregnancy was also complicated with AFLP, with serum glutamic-pyruvic transaminase levels of 586 U/L and lactate dehydrogenase levels of 863 U/L. The infant at birth weighed 960 g, required resuscitation with bag and mask for 30 seconds, and had Apgar scores of 5 and 7 at 1 minute and 5 minutes, respectively. Immediately after resuscitation, the infant was noted to have respiratory distress (Silverman-Andersen score of 8 of 10). In view of this distress, the infant was shifted to the NICU on a T-piece resuscitator and was started on continuous positive airway pressure at 15 minutes of age with a positive end-expiratory pressure of 5 cm and fraction of inspired oxygen of 0.50. Chest radiograph revealed surfactant deficiency. Surfactant (INSURE [intubation, surfactant administration, and extubation]) was given at 2 and 6 hours after birth in view of persistent respiratory distress and increased fraction of inspired oxygen requirement, respectively. She also had poor circulation, was off-color, and had increased capillary perfusion starting from 2 hours after birth. This shock was initially managed with a …

Unusual clinical manifestations of dengue infection in children in a tertiary care hospital in northeast Thailand

Abstract Background: Dengue virus infection has been a public health concern in Thailand. In the past decades, there has been recent interest concerning unusual clinical manifestations in both dengue fever (DF) and dengue hemorrhagic fever (DHF). Objective: We described the unusual clinical manifestations and outcomes of children with dengue admitted to a tertiary care hospital in northeast Thailand. Materials and Methods: A study was conducted on the 73 patients with serologically confirmed dengue infection admitted to Srinagarind Hospital, a tertiary care facility in northeast Thailand between January 2007 and August 2011. Results: Of the 73 children examined, 42 (57%) were boys and 31 were girls. Their age ranged from 8 months to 14 years (median 11 years). Nine patients developed neurological symptoms, 6 patients had altered consciousness, and 3 patients convulsion. Among 9 patients with neurological symptoms, 1 patient had acute kidney injury, 1 had hepatic failure, and 1 had kidney and liver involvement, mostly associated with fluid resuscitation or prolonged shock. Apart from neurological symptoms, one patient developed infection associated hemophagocytic syndrome and was treated with intravenous immunoglobulin. Two patients died from multiple organ failure, and 1 patient was brought back home in a moribund condition. The other patients recovered completely. Conclusion: Altered consciousness was the most commonly observed unusual neurological manifestation. Patients who did not develop acute kidney injury or liver failure had mild clinical courses and recovered from neurological symptoms without sequelae. Acute kidney injury was associated with fluid overload and/or prolonged shock. Careful fluid management and close monitoring for complications resulted in favorable outcomes.

Penicillin-Resistant Streptococcus Pneumoniae Meningitis With Subsequent Vertebral Osteomyelitis and Choledocholithiasis

Penicillin-resistant Streptococcus pneumoniae (PRSP) meningitis is life threatening disease, and prevention and treatment of complication is important. We recently encountered two PRSP meningitis patients with undescribed complications: vertebral osteomyelitis and choledocholithiasis. Patient 1 was a 65-year-old man who presented with PRSP meningitis, disseminated intravascular coagulation (DIC), infective endocarditis, vertebral osteomyelitis, and choledocholithiasis with gallstones. Patient 2 was a 57-year-old man who presented with PRSP meningitis, DIC, acute renal failure, liver dysfunction, vertebral osteomyelitis, and choledocholithiasis with gallstones. Diffusion-weighted brain MRI of both patients revealed high-intensity areas in the posterior horns of the lateral ventricles consistent with ventriculitis. Spinal MRI revealed low-intensity on T1-weighted images and high-intensity on T2-weighted images of the lumbar vertebral bodies and intervertebral disks, consistent with vertebral osteomyelitis. Technetium-99m bone scans revealed accumulation in the lumbar vertebrae. Computed tomography (CT) scans on admission revealed no gallstones, whereas CT scans after abdominal pain or liver dysfunction revealed choledocholithiasis and gallstones. Vertebral osteomyelitis and choledocholithiasis should be noted as possible complications of PRSP meningitis. J Med Cases. 2014;5(2):108-112 doi: http://dx.doi.org/10.14740/jmc1598e

Hepatoprotective Action of Echinophora platyloba DC Leaves Against Acute Toxicity of Acetaminophen in Rats

ABSTRACTContext: Acetaminophen, an analgesic and antipyretic drug, causes fulminant hepatic injury at high doses. Objective: This study evaluated the effects of Echinophora platyloba extract on acetaminophen-induced hepatotoxicity in rats. Materials and methods: Forty-eight rats were divided into six groups. The first (control) and second (test without treatment) groups were administered the solvent of the drug in the morning (08:00) and evening (16:00) on days 1 and 2 but, the third, fourth, and fifth groups received 200, 500, and 1,000 mg/kg b.w E. platyloba extract by gavage on the same days, respectively. The sixth group (positive control) received 200 mg/kg b.w silymarin. Then all groups, except the control group, received 400 mg/kg acetaminophen by gavage on day 2 (10:00). After 24 hr, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), malondialdehyde (MDA), and antioxidant capacity plus liver catalase (CAT) activity and histopathological studies were determined. Data were analyzed with one-way analysis of variance (ANOVA). Results: Treatment of rats with different doses of E. platyloba extract significantly reduced (p < .05) the elevated serum levels of ALT, AST, ALP, and MDA compared to the untreated group. The effects of 1,000 mg/kg E. platyloba were similar to the control and treated silymarin groups. Moreover, E. platyloba significantly increased the activity of liver CAT and serum antioxidant capacity at different doses. Also, E. platyloba extract improved liver histopathological changes compared with the respective control group. Conclusion: The results suggest that E. platyloba extract has impressive hepatoprotective effects on acute acetaminophen-induced liver injuries.

Macrophage heterogeneity in liver injury and fibrosis

Hepatic macrophages are central in the pathogenesis of chronic liver injury and have been proposed as potential targets in combatting fibrosis. Recent experimental studies in animal models revealed that hepatic macrophages are a remarkably heterogeneous population of immune cells that fulfill diverse functions in homeostasis, disease progression, and regression from injury. These range from clearance of pathogens or cellular debris and maintenance of immunological tolerance in steady state conditions; central roles in initiating and perpetuating inflammation in response to injury; promoting liver fibrosis via activating hepatic stellate cells in chronic liver damage; and, finally, resolution of inflammation and fibrosis by degradation of extracellular matrix and release of anti-inflammatory cytokines. Cellular heterogeneity in the liver is partly explained by the origin of macrophages. Hepatic macrophages can either arise from circulating monocytes, which are recruited to the injured liver via chemokine signals, or from self-renewing embryo-derived local macrophages, termed Kupffer cells. Kupffer cells appear essential for sensing tissue injury and initiating inflammatory responses, while infiltrating Ly-6C(+) monocyte-derived macrophages are linked to chronic inflammation and fibrogenesis. In addition, proliferation of local or recruited macrophages may possibly further contribute to their accumulation in injured liver. During fibrosis regression, monocyte-derived cells differentiate into Ly-6C (Ly6C, Gr1) low expressing 'restorative' macrophages and promote resolution from injury. Understanding the mechanisms that regulate hepatic macrophage heterogeneity, either by monocyte subset recruitment, by promoting restorative macrophage polarization or by impacting distinctive macrophage effector functions, may help to develop novel macrophage subset-targeted therapies for liver injury and fibrosis.

A Child With Acute Liver and Kidney Failure Ongoing Encephalopathy: Effectiveness of Plasmapheresis on Acetaminophen Overdose, A Case Report

Acetaminophen (APAP) is a commonly used analgesic and antypiretic medication. APAP -induced liver necrosis has been studied extensively, but extrahepatic manifestations of APAP toxicity are not described well in the literature. Adolescents and young adults may be more prone to renal insufficiency in the setting of APAP overdose; however, the reason for this finding is unclear. Here we report therapeutic misadventure of APAP-associated acute renal and liver failure and effectiveness of plasmapheresis on hepatic encephalopathy. Int J Clin Pediatr. 2014;3(2):63-65 doi: http://dx.doi.org/10.14740/ijcp143w

Clinical Features and Risk Factors for Severe Complications among Patients with Acute Hepatitis A Virus Infection in The Jeonbuk Province of Korea

The frequency of symptomatic acute HAV infections in adulthood are increasing in Korea. This study analyzes the clinical severity in patients with acute HAV infection and investigates risk factors associated with three severe complications: prolonged cholestasis, acute kidney injury, and acute liver failure. We performed a retrospective analysis of 726 patients diagnosed from January 2006 to December 2010 at three tertiary hospitals in Jeonbuk Province, Republic of Korea with acute HAV infection. In the group of 726 patients, the mean age was 30.3 years, 426 (58.6%) were male, and 34 (4.7%) were HBsAg positive. Severe complications from acute HAV infection occurred as follows: prolonged cholestasis in 33 (4.6%), acute kidney injury in 17 (2.3%), and acute liver failure in 16 (2.2%). Through multivariate analysis, age ≥40 years (OR 2.63, p=0.024) and peak PT (INR) ≥1.5 (OR 5.81, p=0.035) were found to be significant risk factors for prolonged cholestasis. Age ≥40 years (OR 5.24, p=0.002) and female gender (OR 3.11, p=0.036) were significant risk factors for acute kidney injury. Age ≥40 years (OR 6.91, p=0.002), HBsAg positivity (OR 5.02, p=0.049), and peak total bilirubin (OR 1.11, p=0.001) were significant risk factors for acute liver failure. Age ≥40 years, female gender, HBsAg positivity, peak PT (INR) ≥1.5, and peak total bilirubin were significant risk factors for severe complications in acute HAV infections.

Lung Matrix Metalloproteinase Activation following Partial Hepatic Ischemia/Reperfusion Injury in Rats

Purpose. Warm hepatic ischemia-reperfusion (I/R) injury can lead to multiorgan dysfunction. The aim of the present study was to investigate whether acute liver I/R does affect the function and/or structure of remote organs such as lung, kidney, and heart via modulation of extracellular matrix remodelling. Methods. Male Sprague-Dawley rats were subjected to 30 min partial hepatic ischemia by clamping the hepatic artery and the portal vein. After a 60 min reperfusion, liver, lung, kidney, and heart biopsies and blood samples were collected. Serum hepatic enzymes, creatinine, urea, Troponin I and TNF-alpha, and tissue matrix metalloproteinases (MMP-2, MMP-9), myeloperoxidase (MPO), malondialdehyde (MDA), and morphology were monitored. Results. Serum levels of hepatic enzymes and TNF-alpha were concomitantly increased during hepatic I/R. An increase in hepatic MMP-2 and MMP-9 activities was substantiated by tissue morphology alterations. Notably, acute hepatic I/R affect the lung inasmuch as MMP-9 activity and MPO levels were increased. No difference in MMPs and MPO was observed in kidney and heart. Conclusions. Although the underlying mechanism needs further investigation, this is the first study in which the MMP activation in a distant organ is reported; this event is probably TNF-alpha-mediated and the lung appears as the first remote organ to be involved in hepatic I/R injury.

Fatal Nitrofurantoin-Induced Pulmonary Toxicity: A Potentially Preventable Medical Error

Nitrofurantoin is a commonly prescribed urinary antiseptic both for acute treatment and prophylaxis against recurrent urinary tract infections. It is known for its safety, efficacy, tolerability and cost-effectiveness. Rarely, nitrofurantoin can cause acute and chronic lung and liver diseases. Acute pulmonary toxicity due to nitrofurantoin is more common than its chronic form and is probably a hypersensitivity reaction to the drug. In contrast, the chronic pulmonary toxicity appears to be due to cumulative drug exposure leading to chronic inflammation and fibrosis and is therefore an irreversible process. What predisposes to the rare and severe form of acute pulmonary toxicity is unknown. In this case, it appears that renal impairment may have played a role as a predisposing factor.