Centrilobular Veins Research Articles

Transjugular Liver Biopsy: The Key to a Rare Etiology of Cholestatic Hepatitis after Bone Marrow Transplantation

Introduction: Hematopoietic stem cell transplantation (HSCT) is associated with multiple complications, such as sinusoidal obstruction syndrome (SOS) (hepatomegaly, ascites, jaundice, and thrombocytopenia) and graft-versus-host disease (GVHD) (with the skin, gastrointestinal tract, and liver being the main targets). These entities may present overlapping clinical findings, being considered differential diagnoses, but their coexistence is rare. Case Presentation: A 29-year-old male with acute myeloid leukemia underwent HSCT. On day (D)+20, he developed hyperbilirubinemia, pleural effusion, ascites, and painful hepatomegaly. Abdominal ultrasound was suggestive of SOS, and defibrotide was initiated. On D+44, acute cutaneous, intestinal, and hepatic GVHD developed which improved after treatment with methylprednisolone. On D+132, there was worsening cholestasis and abdominal pain. MRCP revealed strictures in several segments of the intrahepatic bile ducts and irregularity of the main bile duct. Due to aggravation of liver enzyme changes and clinical worsening, he was admitted to the Intensive Care Unit. Due to persistence of severe hyperbilirubinemia (30 mg/dL) and thrombocytopenia (30,000 cell/uL), he underwent a hepatic hemodynamic study which revealed a hepatic venous pressure gradient of 10 mm Hg. The transjugular liver biopsy revealed canalicular hepatic cholestasis, bile duct injury, and focal hepatocellular necrosis suggestive of GVHD as well as injury to centrilobular veins and centrilobular necrosis compatible with possible SOS. Mycophenolate mofetil was started, but on D+195, the patient died of septic shock. Discussion/Conclusion: This case is notable for its complexity and for demonstrating the rare coexistence of histological features of SOS and GVHD. Although the clinical and laboratory findings may be sufficient for the diagnosis, it is important to highlight the importance of liver hemodynamic study and transjugular liver biopsy in these patients who often have severe thrombocytopenia, for the characterization and histological confirmation of cholestatic hepatitis, especially when the etiology may be multifactorial.

Assessment of Liver Toxicity in Wistar Rats after Chronic Exposure to Phosphate-Processing Wastewaters from Gafsa-Metlaoui Laundry in Tunisia

In the mining basin of the Gafsa region in southwestern Tunisia, environmental exposure to randomly discharged phosphate-processing wastewaters (PPWW) presents a serious threat to health and the surrounding ecosystems. Thus, the contaminated areas are in continuous deterioration over time. There is a paucity of information on the deleterious effects of this kind of effluent. In the current work, the PPWW characterization showed the presence of high contents of Pb (0.90 ± 0.02 mg/L), Cd (0.35 ± 0.27 mg/L), Cr (0.43 ± 0.1 mg/L) and Fe (215.1 ± 2.41 mg/L), exceeding the permissible limits. To assess the chronic toxicity of the effluent in mammalians, two doses of PPWW (50% and 100%) were administered by gavage to Wistar rats for 28 consecutive days. The results revealed that the two PPWW concentrations significantly increased the plasma biochemical markers (bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH)), compared to untreated animals. Moreover, PPWW treatment severely altered the lipid profile by increasing the contents of triglycerides, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-cholesterol) by 143%, 114%, and 91%, respectively, and significantly reduced the high-density lipoprotein cholesterol (HDL-cholesterol) level by 46%, compared to the control animals. In addition to the significant decrease in activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in the liver of intoxicated rats, the malondialdehyde (MDA) level was remarkably altered. All of these were associated with deep histopathological damages, materialized by dilatation of sinusoids, congestion of the centrilobular vein, and inflammatory cell infiltration. These disturbances were accompanied by metal detection in the liver and blood. Additionally, DNA fragmentation detected in hepatic tissues highlighted the genotoxic effects of PPWW. All of the aforementioned effects occurred in a PPWW dose-dependent manner. These findings evidenced, for the first time, the in vivo-deleterious impacts of this type of effluent on mammalians inhabiting the mining basin area and therefore showed the real threats to which humans, as consumers, could be exposed. Accordingly, there is a dire need to pay special attention to PPWW before being discharged into environmental ecosystems without any prior treatments.

Effect of melatonin on the liver histophysiology of adolescent rats exposed to alcohol

The present study evaluated whether melatonin administered during adolescence can prevent the deleterious effects produced by alcohol on the liver. Thirty albino female rats (Rattus norvegicus albinus), 40 days old, virgins, weighing approximately 150±10g, from the Wistar lineage and were divided into the following groups: I – Adolescent rats that did not receive alcohol and euthanized at 60 days of life; II – Adolescent rats subjected to chronic alcohol consumption and euthanized at 60 days of life; III – Adolescent rats subjected to chronic alcohol consumption and simultaneously treated with melatonin, and euthanized at 60 days of life. The collected organs underwent histological processing and to obtain the results, morphometric, histopathological and histochemical analyzes were performed. Alcohol was administered by gavage. intragastric injection at a dosage of 3 g/Kg of ethyl alcohol in the rats of groups II and III for 20 days. Melatonin was administered in daily injections of 0.8 mg/Kg, always at the beginning of the night, intraperitoneally for 20 days. When analyzing the weight of the animals, no significant difference was observed between the groups. The animals in group II presented alterations in the livers such as congestion of the centrilobular vein, hepatocellular ballooning, microgoticular steatosis, leukocyte infiltrate, several pyknotic nuclei in the livers, increase in lobular parenchyma and reduction in non-lobular parenchyma, greater deposition of collagen and reduction of glycogen. Melatonin treatment prevented all these changes. With this, we can conclude that melatonin has great therapeutic potential in the prevention of liver damage in adolescent rats subjected to moderate alcohol consumption, in addition to positive effects on the deposition of collagen and glycogen in the liver.

Zonated quantification of immunohistochemistry in normal and steatotic livers.

Immunohistochemical stains (IHC) reveal differences between liver lobule zones in health and disease, including nonalcoholic fatty liver disease (NAFLD). However, such differences are difficult to accurately quantify. In NAFLD, the presence of lipid vacuoles from macrovesicular steatosis further hampers interpretation by pathologists. To resolve this, we applied a zonal image analysis method to measure the distribution of hypoxia markers in the liver lobule of steatotic livers.The hypoxia marker pimonidazole was assessed with IHC in the livers of male C57BL/6J mice on standard diet or choline-deficient L-amino acid-defined high-fat diet mimicking NAFLD. Another hypoxia marker, carbonic anhydrase IX, was evaluated by IHC in human liver tissue. Liver lobules were reconstructed in whole slide images, and staining positivity was quantified in different zones in hundreds of liver lobules. This method was able to quantify the physiological oxygen gradient along hepatic sinusoids in normal livers and panlobular spread of the hypoxia in NAFLD and to overcome the pronounced impact of macrovesicular steatosis on IHC. In a proof-of-concept study with an assessment of the parenchyma between centrilobular veins in human liver biopsies, carbonic anhydrase IX could be quantified correctly as well.The method of zonated quantification of IHC objectively quantifies the difference in zonal distribution of hypoxia markers (used as an example) between normal and NAFLD livers both in whole liver as well as in liver biopsy specimens. It constitutes a tool for liver pathologists to support visual interpretation and estimate the impact of steatosis on IHC results.

Eugenia gracillima essential oil has pharmaceutical applications in pain and inflammation without toxic effects in mice

Ethnopharmacological relevanceEugenia gracillima is widely used by the population in the manufacture of pulps and jellies, with popular reports of its use in the treatment of infections in the urinary system, respiratory and dermatological problems. A previous study reports that EO from E. gracillima leaves proved to be a promising antioxidant agent in combating the promastigote forms of protozoa. Despite this, this species has been little studied due to its pharmacological properties. Study objectiveIn this study, an essential oil extracted (EO) from Eugenia gracillima leaves was evaluated for its acute toxicity and anti-inflammatory, antinociceptive and behavioral effects in mice. MethodsThe EO was obtained by hydrodistillation, and the composition analysis was performed by gas chromatography coupled to mass spectrometry. Acute toxicity assessment was performed with observation of hematological parameters and histopathological evaluation, as well as tests to investigate antinociceptive, anti-inflammatory activities and behavioral effects. ResultsChromatographic analysis showed D-germacrene (16.10%), γ-muurolene-g (15.60%) and bicyclogermacrene (8.53%) as the majority of compounds. In the toxicity evaluation, no death or physiological changes were observed in mice treated with a single oral dose of up to 5000 mg/kg, and it did not lyse erythrocytes in vitro. The hematological parameters evaluated were not changed after treatment; however, 5,000 mg/kg promoted an increase in transaminase levels. In the histopathological evaluation, only the animals that received the dose of 5000 mg/kg showed discrete leukocyte infiltration around the centrilobular vein in the liver. Antinociceptive activity was detected through tests of acetic acid-induced writhing, formalin, and tail flick, promoted in part by the opioid receptor pathway. In the evaluation of anti-inflammatory activity, a reduction in inflammation was observed in the paw edema test and a decrease in the migration of leukocytes and neutrophils in the peritonitis test. The open field and elevated plus maze tests showed that EO did not affect the animals' motor functions or exploratory activity. ConclusionIt was concluded that the essential oil of E. gracillima has potential for the development of pharmaceutical formulations with analgesic and anti-inflammatory actions in non-toxic concentrations.

Norcantharidin toxicity profile: an in vivo murine study.

Norcantharidin (NCTD) is the demethylated analog of cantharidin, with allegedly reduced toxicity. However, there is still limited information regarding its posology and potential risk in its use in cancer treatment. Healthy BDF1 mice were intraperitoneally administered with norcantharidin (0, 3, 6, 12, and 25mg/kg) every 24h for 6days. Survivor mice were euthanized, and the brain, lungs, kidneys, spleen, and liver were procured for enzymatic and histopathological analysis in the liver and kidney. DL50 were 8.86mg/kg for females and 11.77mg/kg for males. The treatments with 3.0mg/kg and 6.0mg/kg significantly modified the phosphorylase, alanine transaminase, and γ-glutamyl transferase activities; however, an organ-specific response was detected. A significant dose-dependent decrease was observed in the kidney for ROS, while the liver had the opposite effect. Histopathological analysis revealed a significant elevation in hepatocytes' nuclei average size and total area (3mg/kg), as well as centrilobular vein and adjacent sinusoidal capillaries showed a significant difference. The portal triad presented a significant difference in veins and capillarity count in 6mg/kg. Renal samples showed cortex convoluted tubules' average size significantly augmented in both doses' groups, and tubule count was found augmented in 6mg/kg. These physiological effects of NCTD can be exploited as treatment strategies if able to operate in an established posology and proper testing.

High-resolution (7-T) Liver MRI for Pathologic Examination.

HomeRadiologyVol. 306, No. 1 PreviousNext Reviews and CommentaryFree AccessImages in RadiologyHigh-resolution (7-T) Liver MRI for Pathologic ExaminationJérémy Dana , Aïna VenkatasamyJérémy Dana , Aïna VenkatasamyAuthor AffiliationsFrom the Institut de Recherche sur les Maladies Virales et Hépatiques, Université de Strasbourg, Inserm, U1110, 3 Rue Koeberlé, 67000 Strasbourg, France (J.D.); Institut Hospitalo-Universitaire, Strasbourg, France (J.D., A.V.); Department of Diagnostic Radiology, McGill University Health Centre, Montreal, Canada (J.D.); Streinth Laboratory (Stress Response and Innovative Therapies), Inserm UMR_S 1113 IRFAC, Interface Recherche Fondamentale et Appliquée à la Cancérologie, Strasbourg, France (A.V.); and Department of Radiology–Medical Physics, University Hospital Freiburg, Freiburg, Germany (A.V.).Address correspondence to J.D. (email: [email protected]).Jérémy Dana Aïna VenkatasamyPublished Online:Sep 6 2022https://doi.org/10.1148/radiol.220410MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In Online supplemental material is available for this article.Two different liver samples from patients who underwent surgical resection were imaged with a 7-T MRI scanner by using fat-suppressed fast spin-echo T2-weighted sequence, reaching spatial resolution of 75 × 75 × 200 μm in 2 hours.An MRI scan clearly demonstrated the homogeneous architecture of the normal liver (Figure) and identified the primary liver lobule, with its centrilobular vein and peripheral portal tracts (Figure, B and C) within the interlobular delineations (Figure, B). In stage 2 fibrotic liver (Fig E1 [online]), an MRI scan of the liver sample demonstrated correlation with pathologic findings, easily identifying the same fibrous portal bridges (Fig E1A and E1B [online]) and enlarged fibrous portal tracts (Fig E1A and E1B [online]), thus enabling a similar grading of fibrosis. With a spatial resolution close to that of the pathologic examination, MRI enabled an easier depiction of the liver lobule boundaries, allowing early detection of fibrosis-related architectural distortion. Additionally, the specimen remained intact, as no specific preparation was required for the MRI scan, and could undergo standard pathologic processing after image acquisition.Images show radiologic-pathologic correlation of normal liver. (A) Fat-suppressed T2-weighted MRI scan, with a spatial resolution of 75 × 75 × 200 μm, shows the homogeneous architecture of normal liver. (B) MRI scan (magnified image) depicts the anatomy of the primary liver lobule with its centrilobular vein (arrowhead) and peripheral portal venous tracts (arrow) within the interlobular delineations (star). (C) Mirrored pathologic slide, with Masson trichrome staining at four times magnification, identifies the liver lobule with the centrilobular vein (arrowhead) and peripheral portal tracts (arrow) within the interlobular delineations (black lines). (D) Schematic representation of the primary liver lobule with the centrilobular vein (central blue dot) and peripheral portal venous tracts (arrow).Download as PowerPointOpen in Image Viewer Disclosures of conflicts of interest: J.D. Research grant from the French Society of Radiology. A.V. Support from Bracco to attend RSNA 2021; faculty member for ESHNR.AcknowledgmentsWe thank Chrystelle Po, PhD (ICube UMR 7357, Université de Strasbourg/CNRS, Fédération de Médecine Translationnelle de Strasbourg, France), Antonin Fattori, MD (Département de Pathologie, Hôpitaux Universitaires de Strasbourg, France), Catherine Schuster, PhD (Université de Strasbourg, Inserm, Institut de Recherche sur les Maladies Virales et Hépatiques UMR_S1110, Strasbourg, France), Thomas F. Baumert, MD, PhD (Université de Strasbourg, Inserm, Institut de Recherche sur les Maladies Virales et Hépatiques UMR_S1110, Strasbourg, France), Benoit Gallix, MD, PhD (Institut Hospitalo-Universitaire, Strasbourg, France), and Pr Patrick Pessaux, MD, PhD (Département de Chirurgie Viscérale et Digestive, Pôle Hépato-digestif, Nouvel Hôpital Civil, Hôpitaux Universitaires de Strasbourg, Strasbourg, France) for their crucial contribution. Supported by French state funds managed within the "Plan Investissements d’Avenir" and by the ANR (ANR-10-IAHU-02 to B.G.), the ARC, Paris and Institut Hospitalo-Universitaire, Strasbourg (TheraHCC 2.0 and IHUARC2019 to T.F.B.), the European Union (ERC-AdG-2014-671231-HEPCIR and ERC-AdG-2020-667273-FIBCAN to T.F.B.), ANRS, Paris (ECTZ160436 and ECTZ103701 to T.F.B), the Foundation of the University of Strasbourg (HEPKIN to T.F.B.), and the Institut Universitaire de France (T.F.B.). This work has been published under the framework of the LABEX ANR-10-LABX-0028_HEPSYS and Inserm Plan Cancer.Article HistoryReceived: Feb 23 2022Revision requested: Mar 22 2022Revision received: Apr 9 2022Accepted: Apr 25 2022Published online: Sept 06 2022Published in print: Jan 2023 FiguresReferencesRelatedDetailsRecommended Articles A Comprehensive Approach to Hepatic Vascular DiseaseRadioGraphics2017Volume: 37Issue: 3pp. 813-836Imaging Findings of Congestive HepatopathyRadioGraphics2016Volume: 36Issue: 4pp. 1024-1037Noninvasive Staging of Liver Fibrosis Using 5-Minute Delayed Dual-Energy CT: Comparison with US Elastography and Correlation with Histologic FindingsRadiology2021Volume: 298Issue: 3pp. 600-608Catheter-directed Intraportal Delivery of Endothelial Cell Therapy for Liver Regeneration: A Feasibility Study in a Large-Animal Model of CirrhosisRadiology2017Volume: 285Issue: 1pp. 114-123Pulmonary Functional Imaging: Part 1—State-of-the-Art Technical and Physiologic UnderpinningsRadiology2021Volume: 299Issue: 3pp. 508-523See More RSNA Education Exhibits Radiological-Pathological Correlation in Diffuse Lung Diseases Using Ultra-High-Resolution Computed Tomography (U-HRCT): From Miller’s to Reid’s LobuleDigital Posters2019Peribronchovascular Disease on CT: Diagnostic Approach and Imaging FindingsDigital Posters2020Imaging of Hepatic Periportal Lesions and Perivenous LesionsDigital Posters2018 RSNA Case Collection Arterioportal fistulaRSNA Case Collection2021Hepatic AngiosarcomaRSNA Case Collection2021Perihilar Cholangiocarcinoma RSNA Case Collection2021 Vol. 306, No. 1 Supplemental MaterialMetrics Altmetric Score PDF download

Sinusoidal obstruction syndrome after liver transplantation: A multicenter observational study.

Sinusoidal obstruction syndrome after liver transplantation: A multicenter observational study.

The Protective Effect of Heme Oxygenase-1 on Liver Injury Caused by DON-Induced Oxidative Stress and Cytotoxicity.

Deoxynivalenol (DON) is a kind of Fusarium toxin that can cause a variety of toxic effects. Oxidative stress and DNA damage play a critical role in the toxicity of DON. However, previous studies focused more on acute toxicity in vivo/vitro models and lacked subchronic toxicity study in vivo. The potentially harmful effect of DON given at doses comparable to the daily human consumption in target organs, especially the liver, which is the main detoxification organ of DON, is also still not fully understood. Otherwise, Heme Oxygenase-1 (HO-1) has also reduced cell damage under the DON condition according to our previous study. Therefore, we used a rodent model that mimicked daily human exposure to DON and further explored its mechanism of toxic effects on liver tissue and Hepa 1–6 cell line. We also used adeno-associated virus (AAV)-modified HO-1 expressing by tail vein injection and constructed lentivirus-Hepa 1–6 cell line for mimicking HO-1 protective ability under the DON condition. The main results showed that both 30 d and 90 d exposures of DON could cause low-grade inflammatory infiltration around hepatic centrilobular veins. The reactive oxygen species (ROS) and 8-hydroxy-2 deoxyguanosine (8-OHdG) increased during DON exposure, indicating oxidation stress and DNA damage. Significantly, AAV-mediated liver-specific overexpression of HO-1 reduced DON-induced liver damage and indirectly protected the abilities of antioxidant enzyme/DNA damage repair system, while AAV-mediated silence of HO-1 produced the opposite effect. In addition, we found that overexpression of HO-1 could enhance autophagy and combined it with an antioxidant enzyme/DNA damage repair system to inhibit DON-induced hepatocyte damage. Altogether, these data suggest that HO-1 reduces the oxidative stress and DNA damage caused by DON sub-chronic exposure through maintaining DNA repair, antioxidant activity, as well as autophagy.

P-47 HISTOPATHOLOGICAL ANALYSIS OF 10-YEAR PROTOCOL LIVER ALLOGRAFT BIOPSY OF ASYMPTOMATIC PEDIATRIC RECIPIENTS FROM A SINGLE BRAZILIAN CENTER

Liver transplant (LT) is the main therapeutic procedure for irreversible liver failure. Protocol liver biopsies during post-transplant follow-up in pediatric recipients with stable graft function have been done in order to identify structural changes. A more specific score, LAFSc, to analyze fibrosis and inflammation on liver allografts has been validated recently. To describe the prevalence of histological liver abnormalities in asymptomatic pediatric patients after ten years following LT from a Brazilian single center comparing two different scoring methods. Cross-sectional study of analysis of protocol percutaneous liver biopsies performed in patients who underwent liver transplant before the age of 18 years, of both genders, asymptomatic, using Tacrolimus for immunosuppression and at least 10-years post-liver transplant. From 97 recipients, 21 met inclusion criteria and had stable liver graft function. A single experienced pathologist assessed histopathological features comparing METAVIR scoring system and LAFSc. Mean follow-up was 12.8 (+/- 2.1) years after post-LT. TAC mean daily dose during biopsy time was 4mg (+/- 1.7) with mean serum level of 4.04. METAVIR scoring system pointed 10 recipients with any degree of fibrosis and 13 with inflammation findings in protocol biopsies. However, using LAFSc scoring system, 13 patients scored for abnormal findings in any of the three zones analysed, although 8 of these had total score of mild fibrosis (1-3). Of the three zones analysed in LAFSc, the highest scores were found in portal space. Centrilobular vein zone was the most affected, documented in 11 recipients. We observed a higher prevalence of abnormal findings using the new allograft fibrosis scoring system – LAFSc. It also showed more specifically the degree and location of fibrosis within hepatic lobule compared to METAVIR. Compared to other LT reports, we observed lower rates of chronic allograft hepatitis and fibrosis at 10 years.

Review on diagnostic criteria of hepatic sinusoidal obstruction syndrome

Hepatic sinusoidal obstruction syndrome (HSOS) is a kind of hepatic vascular disease which is characterized by damage to hepatic sinusoidal endothelial cells, centrilobular hepatic vein and/or interlobular vein, resulting in stenosis or lumen occlusion, hepatic injury and acute sinusoidal portal hypertension. Generally, most patients with HSOS have mild manifestations, but in severely ill patients, the disease can lead to multiple organ dysfunction/failure, and the mortality rate can be as high as 70%-80%. Therefore, it is important to identify and treat HSOS as soon as possible. This paper introduces the current clinical diagnostic criteria of HSOS, including the Modified Seattle and Baltimore Criteria along with "Nanjing Criteria", and reviews their characteristics, scope of application and limitations.

Triazole fungicides induce hepatic lesions and metabolic disorders in rats

Pesticides are chemicals used in the treatment of agricultural products to increase production to meet growing consumer’s demand. Several studies have shown the toxic effects of these substances in humans as endocrine disrupters. The objective of our study is to highlight the toxic effects of hexaconazole in rats; a fungicide widely used in agriculture in Morocco. 16 rats received 100 mg/kg/day of hexaconazole orally via diet for 12 weeks. Biochemical analyses of the blood of treated animals showed a significant increase in creatinine, bilirubin, ASAT, ALAT and LDH levels, which would indicate toxicity in different organs. Also, a histological study of the liver was carried out. Microscopic observations showed several liver damages, such as centrilobular vein congestion, necrosis, immune cells infiltration, cholestasis, microvesicular and macrovesicular steatosis. These biochemical and histological results show that exposure to hexaconazole can cause liver and kidney damage. This pesticide would present an actual or potential danger to the consumer’s health.

Pulmonary Hypoplasia Associated with Ascites and Hydrothorax in a Newborn Pig

Background: Pulmonary hypoplasia is characterized by incomplete development of the lungs, owing to congenital defectsor the action of toxic substances. Moreover, it has rarely been described in pigs. Ascites or hydroperitoneum is characterized by the presence of fluid inside the abdominal cavity and does not generally cause changes in the abdominal organs. However, hydrothorax, characterized by the presence of fluid within the thoracic cavity, is responsible for the compression of thoracic organs and consequent heart and respiratory failure. This study aims to describe a case of congenital pulmonary hypoplasia associated with ascites and hydrothorax in a newborn pig.Case: A male neonate Landrace pig that died shortly after delivery was presented for necropsy with increased abdominal volume and bilateral extension of the pelvic limbs. The pig belonged to a litter of 13 piglets, four of which died shortly after birth. The rest of the piglets were poorly developed, but only one was presented for necropsy. Significant external changes, along with permanent distension, interpreted as arthrogriposis, were observed in the pelvic limbs. The skin of the ventral abdominal region was thin, with evidence of all blood vessels, interpreted as telangectasis. An internal examination revealed the presence of a slightly yellowish liquid in the thoracic and abdominal cavities, interpreted as hydrothorax and ascites, respectively. The lungs were reduced in size, indicating pulmonary hypoplasia. The liver had rounded edges, which were dark red and firm, with an irregular surface. Significant microscopic findings were observed in the lungs, which were divided by fibrous connective tissue and showed evidence of small and atrophied alveoli. Furthermore, connective tissue was observed around the peribronchiolar regions and underdeveloped cartilage around the airways. The liver showed dilation of the centrilobular veins. Moreover, the sinusoids were filled with erythrocytes, indicating congestion.Discussion: Pulmonary hypoplasia is a rare birth defect in pigs and can be accompanied by malformations of other organs, including anasarca. Pulmonary hypoplasia is caused by conditions that compress the lungs, such as congenital diaphragmatic hernia, intrathoracic masses, and pleural effusion or malformations in the chest cavity. However, none of these conditions were observed in the current case. Instead, the histopathological changes observed in the lungs were characteristic of pulmonary hypoplasia. A microscopic examination revealed that the hypoplastic lungs showed a reduced number of alveoli, replacement of the peribronchiolar smooth muscle by the connective tissue, and underdeveloped cartilage around the airways, all of which are characteristic of pulmonary hypoplasia. Vascular telangiectasia is characterized by abdominal distention due to a marked ascitic condition. Invariably, ascitic fluid accumulation results from changes in hydrodynamic parameters. The hydrothorax observed in this animal was suggestive of changes in the hydrodynamic parameters, which consequently led to fluid accumulation in the chest cavity. This has been previously described in a newborn pig infected with Clostridium difficile. The permanently and bilaterally extended pelvic joints observed at birth in this animal were interpreted as arthrogriposis. This change is attributed to various factors, such as fetal paralysis in pigs that ingest toxic substances like alkaloids present in Conium maculatum and in the stalks of Nicotiana tabacum and Datura stramunium. The literature describes pelvic limb paralysis in Landrace pigs as a genetically inherited disorder. However, it was not possible for us to establish the cause of arthrogriposis for certain in this pig.

Heme oxygenase-1 regulates autophagy through carbon-oxygen to alleviate deoxynivalenol-induced hepatic damage.

Deoxynivalenol (DON) cannot be totally removed due to its stable chemical characteristics and chronic exposure to low doses of DON causes significant toxic effects in humans and animals. However, the potential hazard of such low-dose exposure in target organs still remains not completely understood, especially in liver, which is mainly responsible for detoxification of DON. In the present study, we demonstrated for the first time that estimated human daily DON exposure (25μg/kg bw) for 30 and 90days caused low-grade inflammatory infiltration around hepatic centrilobular veins, elevated systemic IL-1β, IL-6 and TNF-α and impaired liver function evidenced by increased serum ALT activity. At the molecular level, expressions of autophagy-related proteins as well as Cleaved Caspase-3 and Cleaved Caspase-7 were upregulated during DON exposure, which indicated the activation of autophagy and apoptosis. Importantly, AAV-mediated liver-specific overexpression of HO-1 reversed DON-induced liver damages, upregulated autophagy and attenuated apoptosis in liver, while AAV-mediated HO-1 silence aggravated DON-induced liver damages, inhibited autophagy and increased apoptosis. Furthermore, in vitro experiments demonstrated that lentivirus-mediated HO-1 overexpression in Hepa 1-6 cells prolonged the duration of autophagy and delayed the onset of apoptosis. HO-1 silence in Hepa 1-6 cells inhibited activation of autophagy and accelerated occurrence of apoptosis, and these could be recovered by CO pre-treatment. Therefore, we suppose that HO-1 might be a potential research target to protect human and animal from liver injuries induced by low dose of DON exposure.

Effect of haloperidol on centrilobular vein and portal triad of liver in the albino rats during intrauterine life

Haloperidol is first generation antipsychotic used to treat psychosis. Its usage during pregnancy benefits psychotic mother and is indispensable for treating psychiatric emergency situations. Objectives: To evaluate the effects of haloperidol on development of centrilobular vein and portal triad of liver given to albino rats during intrauterine period. Study Design: Experimental study. Setting: PPGMI Animal House, Lahore. Period: July to September 2017. Materials & Methods: Pregnant female rats were randomly divided into three groups A,B and C ,15 rats in each group. Group B & C were given haloperidol in a dose of 0.4mg/kg and 0.8mg/kg body weight by intraperitoneal route whereas group A was considered as control group. Hysterotomy was done on 21st day of gestation and pups were removed. Pups of group A, B and C were designated as A1, B1 and C1. They were grossly examined for any abnormality and liver was removed after dissection. Slides were made and stained to evaluate changes in detailed histological study of centrilobular veins and portal triads. Results: Comparison of centrilobular vein and portal triad of group B1 and C1 with control A1 revealed that there is significant congestion seen in centrilobular veins of group B1 and C1 with P value ≤ 0.001 and signs of inflammation are present in experimental groups where were significant as compared to control group A1 with P value ≤ 0.001. Conclusion: Haloperidol, given during intrauterine life is responsible for initiating cell injury sequelae in the developing liver of fetal albino rats and must be given with caution if necessary.

Effect of haloperidol on centrilobular vein and portal triad of liver in the albino rats during intrauterine life

Background: Acute poisoning in children is the third most common emergency with significant economical burden. Objectives: This study was carried out to elucidate the clinical and demographic pattern and outcome of acute poisoning in children at local University Hospital of South Punjab. Study Design: Retrospective study. Setting: Pediatric Medicine Department of Nishtar Medical University, Multan. Study Period: January 1st – December 31st 2016. Materials and Methods: This one year hospital based study included 74 children up to 12 years admitted with acute poisoning. The data was extracted from clinical charts. Clinical, demographic and outcome data was extracted and analyzed. Mean and standard deviation are calculated for continuous variables and frequencies with percentages for categorical variables. The data is presented in tables and figures. Results: A total of 74 children with poisoning were admitted during study period (total admission–3107) giving annual incidence of 2.38 %. Males predominated (n=49, 66 %) the study population. Fifty four percent (n=40) of the children were in 13 – 59 months age group. Majority of the children were admitted due to accidental poison ingestion (n=65, 87.8%), through emergency (n=68, 92%) department, brought from urban areas (n=38, 51.4%), and within 1 hour of exposure (n=41, 55.4%). Most common poisons ingested were pesticides (n=29, 39%), kerosene oil (n=13, 17.57%) and Paraphenylene diamine (Kala pathar) (n=11, 14.86%). Most common system specific symptoms belonged to cardiovascular system (54 %) followed by nervous system (51 %) and respiratory system (42 %). Median hospital stay of the poisoning cases was 2 days (min. 1, max. 17). Poisoning associated mortality rate was 16.2 % (n=12). Kala pathar ingestion was the only significant factor associated with mortality (p-value 0.04). Conclusion: Accidental ingestion of non – pharmacological agents at home is most common in children < 5 years of age at our set – up. Mortality rate due to acute poisoning is high in children. Parents education for safe placement of poisoning agents, set – up of regional poison control centers and healthcare workers training on management of such cases will help curtailing this problem.

Hepatic and Renal Toxicity Induced by TiO2 Nanoparticles in Rats: A Morphological and Metabonomic Study.

Titanium dioxide (TiO2) nanoparticles (NPs) are produced abundantly and are frequently used as a white pigment in the manufacture of paints, foods, paper, and toothpaste. Despite the wide ranges of uses, there is a lack of information on the impact of NPs on animal and human health. In the present study, rats were exposed to different doses of TiO2 nanoparticles and sacrificed, respectively, 4 days, 1 month, and 2 months after treatment. Dosage of TiO2 in tissues was performed by ICP-AES and revealed an important accumulation of TiO2 in the liver. The nanoparticles induced morphological and physiological alterations in liver and kidney. In the liver, these alterations mainly affect the hepatocytes located around the centrilobular veins. These cells were the site of an oxidative stress evidenced by immunocytochemical detection of 4-hydroxynonenal (4-HNE). Kupffer cells are also the site of an important oxidative stress following the massive internalization of TiO2 nanoparticles. Enzymatic markers of liver and kidney functions (such as AST and uric acid) are also disrupted only in animals exposed to highest doses. The metabonomic approach allowed us to detect modifications in urine samples already detectable after 4 days in animals treated at the lowest dose. This metabonomic pattern testifies an oxidative stress as well as renal and hepatic alterations.

Histopathological and biochemical assessment of liver damage in albino Wistar rats treated with cytotoxic platinum compounds in combination with 5-fluorouracil.

IntroductionChemotherapy-induced hepatotoxicity in cancer patients often results in cessation of therapy and prevents completion of the treatment plan. The entire pathological description and comparison of hepatic damage induced by oxaliplatin or cisplatin in combination with 5-fluorouracil (5-FU) is not adequately reported. This study reports histopathological assessment of hepatotoxicity of a non-tumor bearing organ in rats treated with 5-FU, oxaliplatin and cisplatin (CDDP).Material and methodsChanges in hepatic biochemical profile of 36 albino Wistar rats equally divided into different treatment groups with cisplatin, oxaliplatin, 5-FU, cisplatin plus 5-FU and oxaliplatin plus 5-FU were compared with a group of rats treated with normal saline (control group). At the end of treatments, hepatic tissues were taken for blinded histopathological assessment by light microscopy.ResultsSerum glutamate pyruvate transaminase and serum glutamic-oxaloacetic transaminase levels were disrupted in rats treated with 5-FU alone and in combination with cisplatin or oxaliplatin. Hepatocellular injuries, e.g. sinusoidal dilatation, venular fibrosis and centrilobular vein injury induced by oxaliplatin were intensified in treatment groups also receiving 5-FU, manifested as massive architectural distortion, periportal fibrosis, hepatic cord degeneration and cystic lesions with demarcated margins. Hepatocellular degenerative sequence and abnormally dilated central hepatic vein was shown in the cisplatin plus 5-FU treatment group with hemorrhage and blood filled sinusoids.ConclusionsOxaliplatin-associated cystic lesions were intensified in rats treated with a combination of 5-FU and oxaliplatin.

Naphthoquine-induced Central Nervous System and Hepatic Vasculocentric Toxicity in the Beagle Dog.

Naphthoquine phosphate (NP) was considered as a partner drug with a promising antimalarial drug candidate. Here we report unexpected adverse clinical signs and microscopic findings in a canine pilot toxicology study with NP. Male and female dogs were dosed daily by oral gavage with NP at 2, 10, or 50 mg/kg/day for a maximum of 14 days. NP was not tolerated at ≥10 mg/kg/day; several animals were sacrificed in moribund condition and marked neurological clinical signs were noted at 50 mg/kg/day. The main microscopic observation was central nervous system vasculocentric inflammation (mainly lymphocytes and macrophages) in the white and gray matter of various regions of the brain at ≥2 mg/kg/day and at lower incidence in the spinal cord at ≥10 mg/kg/day. Vasculocentric microscopic changes predominantly centered on the centrilobular vein were also observed in the liver at ≥2 mg/kg/day. Females were more sensitive than males with comparable NP plasma exposure. In conclusion, under the conditions of this study, the administration of NP to dogs via daily oral gavage for up to 2 weeks was not tolerated causing moribundity, marked neurological clinical signs, and vasculocentric microscopic changes in the central nervous system and the liver.

Oral thearubigins do not protect against acetaminopheninduced hepatotoxicity in mice

Purpose: To investigate the potential protective effect of oral repeated doses of thearubigins against acetaminophen-induced hepatotoxicity in mice.Methods: Mice were randomly divided into six groups (n=8) and administered the following: Control group (saline), acetaminophen group (saline), N-acetylcysteine group (500 mg/kg/day), and thearubigins groups (60, 70, 100 mg/kg/day). The drugs were given orally by gavage for seven days. On day 7, 1 h after the last dose of treatment, the mice (except control group) were given a single dose of acetaminophen (n-acetyl-p-aminophenol, APAP) orally by gavage (350 mg/kg) and then sacrificed 4 h post-APAP intake. Blood was collected for biochemical measurements and their liver were subjected to biochemical and histopathological assessment.Results: The acetaminophen group showed significant increases (p < 0.001) in serum alanine aminotransferase level, hepatic cytochrome P2E1 level, and serum and hepatic malondialdehyde levels. Moreover it showed significant decrease (p < 0.001) in serum and hepatic glutathione levels. Morphologically, the liver sections showed cellular necrosis, vacuolization, and degeneration around the centrilobular veins. Pretreatment with N-acetylcysteine reversed all acetaminophen-induced changes (p < 0.001 for all biomarkers except for hepatic MDA (p = 0.014) while pretreatment with thearubigins failed to reverse any of them.Conclusion: Oral repeated doses of thearubigins failed to protect against acetaminophen-induced hepatotoxicity in mice and didn't affect hepatic cytochrome P2E1 level.Keywords: Acetaminophen, Hepatotoxicity, Thearubigins, N-acetylcysteine, Cellular necrosis, Vacuolization, Hepatic cytochrome P2E1