Portal Spaces Research Articles

Estimating the Concentration of Heavy Metals in Oleander/Pink and white Oleander Plants

Oleander is a large ornamental evergreen shrub that may grow 20–25 ft in height. During the summer months’ large clusters of white, pink, red, or yellow (yellow oleander) flowers appear at the ends of the branches. All parts of the plant contain cardiac glycosides. Oleander is a common source of serious plant poisoning. In South Asia, particularly Sri Lanka, also present in Libya desert and some house gardens with white and pink types, oleander has become a notorious method of suicide. Toxicity is largely characterized by gastrointestinal symptoms and cardiac abnormalities. Tachy or bradydysthythmias may be present in addition to slowed conduction and heart block. Hyperkalemia is common and correlates with severity of poisoning. A specific antidote—digoxin-specific fragment antigen-binding region (Fab region)- is available. In Mediterranean climates oleanders can be expected to bloom from April through October, with the heaviest bloom usually occurring between May and June. Free-flowering varieties like 'Petite Salmon' or 'Mont Blanc' require no period of rest and can flower continuously throughout the year if the weather remains warm. The exact nature of plant poisoning varies from region to region, but certain plants are almost ubiquitous in distribution and among these, Oleander is a garden plant that features in many homes. Incidents of poisoning from these plants are therefore not uncommon and may be the result of accidental exposure or deliberate, suicidal ingestion of the toxic parts. An attempt has been made to review the management principles with regard to toxicity of these plants and survey the literature in order to highlight current concepts in the treatment of poisoning resulting from both plants. Ingestion of its seeds results in a clinical picture similar to digoxin toxicity. It contains cardiac glycosides that are toxic to cardiac myocytes and autonomic system. Cardiac glycosides of oleander cause poisoning by inhibiting plasmalemmal Na+/K+-ATPase. Results: The poisoning effects of plant or their active alkaloids induced infiltration of cells with hemorrhage and sever negative changes in the lung, induce lesions, and infiltration of inflammatory cells into the portal spaces with scattered necrosis of hepatocytes in the liver, cardiac toxicity of the plant in the heart were included, induced varying degrees of hemorrhage, myocardial degeneration, and necrosis. It also induced arrhythmia, sinus bradycardia, and prolonged P-R interval in electrocardiographic records. Conclusions: The toxic effects of N. oleander are mostly related to its inhibitory effects on the Naþ-Kþ ATPase pump in the cellular membrane. However, the exact molecular mechanism involved in the toxicity of N. oleander is not clear.

High-fat diet elicits sex-based differences in liver inflammatory cytokines and redox homeostasis.

Sex differences in metabolic dysfunction-associated steatotic liver disease (MASLD) have been reported. Oxidative stress and inflammation are involved in the progression of MASLD. Thus, we aimed to evaluate liver redox homeostasis and inflammation in male and female rats fed a high-fat diet (HFD). Male and female Wistar rats were divided into the following groups: standard chow diet (SCD) or HFD during 12 weeks. HFD groups of both sexes had higher hepatocyte injury, with no differences between the sexes. Portal space liver inflammation was higher in females-HFD compared to females-SCD, whereas no differences were observed in males. Lobular inflammation and overall liver inflammation were higher in HFD groups, regardless of sex. TNF-α, IL-6, and IL-1β levels were higher in males-HFD compared to males-SCD, but no differences were observed in females. Catalase activity was higher in males compared to females, with no differences between the SCD and HFD groups of both sexes. Glutathione peroxidase activity was higher in females compared to males, with no differences between the SCD and HFD groups in both sexes. Lipid peroxidation was higher in female-SCD when compared to male-SCD, and in both male- and female-HFD compared to SCD groups. Furthermore, both cytoplasmic and nuclear NRF2 staining were lower in the HFD group compared to the SCD group in males. However, female-HFD exhibited reduced nuclear NRF2 staining compared to the female-SCD group. In conclusion, our study demonstrated that while both male and female rats developed metabolic dysfunction-associated steatohepatitis after 12 weeks of HFD, the alterations in inflammatory cytokines and redox balance were sexually dimorphic.

Diagnostic value of identifying location and amount of free gas in the abdominal cavity by multidetector computed tomography in patients with acute gastrointestinal perforation

Objective: To evaluate the relationships between the location and extent of diffusion of free intraperitoneal air by multi-slice spiral CT (MSCT) and between the location and size of acute gastrointestinal perforation. Methods: This was a descriptive case series. We examined abdominal CT images of 33 patients who were treated for intraoperatively confirmed gastrointestinal perforation (excluding appendiceal perforation) in the Department of General Surgery, Nanfang Hospital between January and September 2022. We identified five locations of intraperitoneal air: the subphrenic space, hepatic portal space, mid-abdominal wall, mesenteric space, and pelvic cavity. We allocated the 33 patients to an upper gastrointestinal perforation (n=23) and lower gastrointestinal perforation group (n=10) base on intraoperative findings and analyzed the relationships between the locations of free gas and of gastrointestinal perforation. Additionally, we established two models for analyzing the extent of diffusion of free gas in the abdominal cavity and constructed receiver operating characteristic (ROC) curves to analyze the relationships between the two models and the size of the gastrointestinal perforation. Results: In the upper gastrointestinal perforation group, free gas was located around the hepatic portal area in 91.3% (21/23) of patients: this is a significantly greater proportion than that found in the lower gastrointestinal perforation group (5/10) (P=0.016). In contrast, free gas was located in the mesenteric interspace in 8/10 patients in the lower gastrointestinal perforation group; this is a significantly greater proportion than was found in the upper gastrointestinal perforation group (8.7%, 2/23) (P<0.010). The sensitivity of diagnosis of upper gastrointestinal perforation base on the presence of hepatic portal free gas was 84.8% and the specificity 71.4%. Further, the sensitivity of diagnosis of lower gastrointestinal perforation base on the presence of mesenteric interspace free gas was 80.0% and the specificity 91.3%. The rates of presence of free gas in the subdiaphragmatic area, mid-abdominal wall, and pelvic cavity did not differ significantly between the two groups (all P>0.05). Receiver operating characteristic curves showed that when free gas was present in four or more of the studied locations in the abdominal cavity, the optimal cutoff for perforation diameter was 2 cm, the corresponding sensitivity 66.7%, and the specificity 100%, suggesting that abdominal free gas diffuses extensively when the diameter of the perforation is >2 cm. Another model revealed that when free gas is present in three or more of the studied locations, the optimal cutoff for perforation diameter is 1 cm, corresponding to a sensitivity of 91.7% and specificity of 76.2%; suggesting that free gas is relatively confined in the abdominal cavity when the diameter of the perforation is <1 cm. Conclusion: Identifying which of five locations in the abdominal cavity contains free intraperitoneal air by examining MSCT images can be used to assist in the diagnosis of the location and size of acute gastrointestinal perforations.

Human liver afferent and efferent nerves revealed by 3-D/Airyscan super-resolution imaging.

Neural regulation of hepatic metabolism has long been recognized. However, the detailed afferent and efferent innervation of the human liver has not been systematically characterized. This is largely due to the liver's high lipid and pigment contents, causing false-negative (light scattering and absorption) and false-positive (autofluorescence) results in in-depth fluorescence imaging. Here, to avoid the artifacts in three-dimensional (3-D) liver neurohistology, we embed the bleached human liver in the high-refractive-index polymer for tissue clearing and antifade 3-D/Airyscan super-resolution imaging. Importantly, using the paired substance P (SP, sensory marker) and PGP9.5 (pan-neuronal marker) labeling, we detect the sensory nerves in the portal space, featuring the SP+ varicosities in the PGP9.5+ nerve bundles/fibers, confirming the afferent liver innervation. Also, using the tyrosine hydroxylase (TH, sympathetic marker) labeling, we identify 1) condensed TH+ sympathetic nerves in the portal space, 2) extension of sympathetic nerves from the portal to the intralobular space, in which the TH+ nerve density is 2.6 ± 0.7-fold higher than that of the intralobular space in the human pancreas, and 3) the TH+ nerve fibers and varicosities contacting the ballooning cells, implicating potential sympathetic influence on hepatocytes with macrovesicular fatty change. Finally, using the vesicular acetylcholine transporter (VAChT, parasympathetic marker), PGP9.5, and CK19 (epithelial marker) labeling with panoramic-to-Airyscan super-resolution imaging, we detect and confirm the parasympathetic innervation of the septal bile duct. Overall, our labeling and 3-D/Airyscan imaging approach reveal the hepatic sensory (afferent) and sympathetic and parasympathetic (efferent) innervation, establishing a clinically related setting for high-resolution 3-D liver neurohistology.NEW & NOTEWORTHY We embed the human liver (vs. pancreas, positive control) in the high-refractive-index polymer for tissue clearing and antifade 3-D/Airyscan super-resolution neurohistology. The pancreas-liver comparison reveals: 1) sensory nerves in the hepatoportal space; 2) intralobular sympathetic innervation, including the nerve fibers and varicosities contacting the ballooning hepatocytes; and 3) parasympathetic innervation of the septal bile duct. Our results highlight the sensitivity and resolving power of 3-D/Airyscan super-resolution imaging in human liver neurohistology.

Effect of mild gestational diabetes mellitus on histological, ultrastructural, and quantitative morphometric alterations of rat fetal liver.

Gestational diabetes mellitus (GDM), one of the most common metabolic disorders in pregnancy, impacts maternal and fetal health. This study was designed to assess the effects of mild GDM on the histology, ultrastructure, and morphometry of fetal liver tissue. In this experimental study, twenty pregnant rats were randomly allocated into control and streptozotocin (STZ)-induced diabetic groups. Mild hyperglycemia was induced by intraperitoneal injection of STZ (40 mg/kg/bw) on the 5th day of gestation. At day 19 of gestation, fetal livers were separated and subjected to histological, transmission electron microscopic, and quantitative morphometric examinations. In the GDM group, PAS staining was positive, revealing scattered eosinophilic inclusions in some hepatocytes. Masson trichrome staining was also positive and showed some fibrous tissue as fine fibers in the portal spaces that extended to the central vein. Reticulin staining in the GDM group was focally positive in the areas of fibrosis and the portal spaces. Ultrastructural examination showed pyknotic nuclei, karyolysis, degranulation and vesiculation of the rough endoplasmic reticulum, and degeneration of mitochondria in the GDM group. The morphometric examination demonstrated that the mean area of hepatocytes was significantly lower in the GDM group than in the control group (P<0.05). Moreover, the mean diameter of the central vein and the density of megakaryocytes were significantly higher in the GDM group than in the control group (P<0.05). Uncontrolled mild GDM induced the histological, ultrastructural and morphometric alterations in the fetal liver.

Germline Variant in ZCCHC8 Is Associated with Pulmonary Fibrosis, Bone Marrow Failure, Liver Inflammation, Early Grey Hair and Short Telomer Length

Introduction Telomere biology disorders (TBD) encompass rare genetic conditions that affect telomere function. TBD is associated with a wide range of symptoms, including hematologic, dermatologic, pulmonary, hepatic manifestations. Research is continuously identifying novel variants and genes causative of TBD. In a recent study, Gable et al. (2019) detected a germline missense variant in ZCCHC8 (NM_017612.5:c.557C&amp;gt;T; p.(Pro186Leu)) in a single family with pulmonary fibrosis. This ZCCHC8 variant was associated with short telomere length (TL) and pulmonary fibrosis. To the best of our knowledge, no other families or individuals have been reported to have pathogenic variants in ZCCHC8 and TBD . However, in this abstract, we present data from a second family discovered to harbor a pathogenic variant in ZCCHC8 and to have symptoms of TBD. Methods Family members provided informed consent for genetic testing and underwent trio-based whole-genome sequencing (WGS). DNA isolated from fkin-derived fibroblasts was analyzed in the proband, while DNA from whole blood was used for the parents. To measure TL, we employed Computel (Nersisyan L. et al., 2015) and compared the mean TL to a cohort of patients who also underwent WGS to estimate a relative mean TL. Results: The proband was a 14-year-old male who had pancytopenia and elevated ALAT levels at presentation. A bone marrow biopsy showed a hypocellular bone marrow. A liver biopsy revealed mild centrilobular, pericellular, and portal fibrosis, along with mild inflammation in the portal space, these findings were interpreted as liver regeneration following acute hepatitis. Despite thorough investigations, no explanation for the findings was found. The proband had a history of psychogenic non-epileptic seizures. When the patient was around 20 years of age his hair started to gray. At present, the proband is 23 years old and has not experienced any progression of symptoms. Family history revealed that the proband's father and two second-degree relatives on the paternal side of the family had developed pulmonary fibrosis in the fifth and sixth decade of life as well as early grey hair. Thus, the inheritance pattern of disease related to TBD was autosomal dominant. WGS revealed a heterozygous pathogenic variant in ZCCHC8 (NM_017612.5c.557C&amp;gt;T (p.P186L)) present in the proband and the father which was absent in the mother. The variant was the same as reported by Gable et al. (2019). The variant is not present in gnomAD or COSMIC and it is the only reported pathogenic or likely pathogenic ZCCHC8 missense variant in ClinVar to date. Both the proband and the father exhibited short relative mean TL by Computel estimation. Subsequently, Flow-FISH analysis confirmed that the proband's telomere length was below the 1st percentile. Conclusion Here we present a family with a heterozygous germline variant in ZCCHC8 and TBD including pulmonary fibrosis, pancytopenia, early graying of the hair, and liver disease. Thus, we provide strong evidence of an association between TBD and ZCCHC8.

A Macroscopic and Microscopic Study of Liver in Female Iraqi Green Freshwater Turtle (Chelonia mydas) Linnaeus,1758 during the Active Period

The study aims to provide anatomical and histological information about the liver in female Iraqi green freshwater turtles. Ten female green freshwater turtles (Chelonia mydas) were collected from Shatt Al-Hilla and used in this study. They were anesthetized by chloroform in closed chambers. The anatomical information was recorded and the histological sections of the liver were stained by using hematoxylin and Eosin stains. The result showed that the liver of a female green freshwater turtle (Chelonia mydas) is a large elongated organ. The mean weight of turtles is 735±0.04 gm, and the mean weight of the liver is 28±0.02 gm. The ratio between the weight of the liver to the weight of the body was 3.809 %. The liver of (Chelonia mydas) is formed from three lobes right, left and middle (central) lobes. The right lobe is the large one with an average weight of 13 ±0.022 gm. It looks like a square and has two surfaces ventral and dorsal (visceral) surface. The left lobe is smaller than the right with an average weight of 9±0.05gm, and its shape is rectangular. The middle lobe is rounded and small. Its mean weight is 7±0.01gm. Histologically, the liver is covered by mesothelium under its connective tissue layer as a hepatic capsule which divided the liver into lobules in the shape of hexagons with portal spaces, from the central to the walls of the hepatocyte.

Libertecture: A catalogue of libertarian spaces

In this article we identify spaces and built environments that have the effect of placing libertarian thinking in urban contexts, using the term ‘libertecture’ to refer to the way that these architectures convey principles of personal liberty and unfettered market activity. These ideas are thus embedded in cities via the design, architecture, management and function of an emerging array of buildings, districts and infrastructures. Locating our analysis in cultural political economy, we believe that these libertectures are important because of the way that they refract and amplify divisive ideas into the social spaces and thinking of residents and citizens. Whereas neoliberal urbanism was seen as undermining socially just cities, libertarian ideas amplified by new built environments may presage more atomised, unequal and unsustainable urban conditions, potentially foreclosing the identification of more just alternatives and democratic forms. We offer a ‘catalogue’ of seven forms of libertecture: private cities, residential exits, portal spaces, fiscal lockers, pioneer exclaves, infinity spaces, and necrotectures. We conclude that the manifestation of libertarian thinking in spaces and city forms is an important object of study for urban studies as it considers challenges to inclusive and sustainable forms of urban governance.

Postinor®-2 and Norinyl®-1/35 Impairs Hepatic Functions and Morphology in Rat Models: Evidences of Oxidative Stress as a Mechanism Pathway

Oral contraceptives such as Postinor®-2 and Norinyl®-1/35 are easily accessible contraceptive pills by women of reproductive age (15 – 49 years). The hepatic effects of these drugs were evaluated in rats. A total of 25 adult female Wistar rats purchased from the animal house, College of Health Sciences, Benue State University, Makurdi were randomly divided into five groups (1 – 5) of five rats each, and acclimatized for 14 days. After which the groups were treated as follows: group 1 (100mg/kg body weight of normal saline), group 2 (0.10mg/kg body weight of Postinor®-2), group 3 (0.20mg/kg body weight of Postinor®-2), group 4 (0.10mg/kg body weight of Norinyl®-1/35) and group 5 (0.20 mg/kg body weight of Norinyl®-1/35) for 14 days, and then the rats were fasted overnight and sacrificed. Blood samples and organs (liver) were collected for biochemical and histological analysis respectively. Postinor®-2 and Norinyl®-1/35 had no significant effect on the body weight and liver weight of rats across groups. For liver function enzymes; groups 2, 3, 4 and 5 all showed a statistically significant increase in mean compared to the control group for ALT. For ALP, only group 4 (86.69±2.54) showed a statistically significant increase in mean in comparison to group 1, while for AST, groups 2 and 4 showed a significant decrease in mean compared to group 1. For oxidative stress markers MDA and SOD, groups 2 and 3 showed a statistically significant increase and decrease respectively, when compared to the control group. Group 1 showed normal liver histology, while those in groups 2 and 3 showed a markedly distorted liver histology, with widely dilated sinusoids, degenerated endothelial cells with neutrophilic and lymphocytic infiltrates in portal spaces. the results obtained in this study pointed clearly that of the two drugs tested, Postinor®-2 had more deleterious effects than Norinyl®-1/35 on the liver of the adult female Wistar rats. It may therefore be inferred from the result of this study that Postinor®-2 should be taken according to prescription or should be avoided, because its frequent consumption and abuse can result in tissue damage in human organs.

Acute severe hepatitis as a presenting symptom in clinically stable patients admitted with SARS-CoV-2 Omicron infection.

Suggested mechanisms for SARS-CoV-2 direct liver infection have been proposed by others to involve both cholangiocytes and hepatocytes. Early clinical studies have highlighted abnormal liver biochemistry with COVID-19 infection as often not being severe, with elevated liver enzymes <5X the upper limit of normal. Liver enzymes were evaluated and compared in patients admitted with a diagnosis of COVID-19 in a deidentified Internal Medicine-Medical Teaching Unit/hospitalist admission laboratory database. Comparisons in the incidence of severe liver injury (alanine aminotransferase >10 times upper limit of normal) were made for patients with pre-Omicron SARS-CoV-2 (November 30, 2019, to December 15, 2021) and Omicron SARS-CoV-2 (December 15, 2021, to April 15, 2022). Comprehensive hospital health records were also reviewed for the 2 patient cases discussed. One patient had a liver biopsy that was evaluated with H&E and immunohistochemistry staining using an antibody against COVID-19 spike protein. The evaluation of a deidentified admissions laboratory database found the incidence of severe liver injury was 0.42% with Omicron versus 0.30% with pre-Omicron variants of COVID-19. In both patient cases discussed, abnormal liver biochemistry and a negative comprehensive workup strongly suggest COVID-19 as the cause of severe liver injury. In the one patient with liver biopsy, immunohistochemistry staining suggests SARS-CoV-2 presence in the portal and lobular spaces in association with immune cell infiltration. The Omicron variant of SARS-CoV-2 should be considered in the differential diagnosis of severe acute liver injury. Our observation suggests that this new variant, either through direct liver infection and/or mediating immune dysfunction, can result in severe liver injury.

Focal Nodular Hyperplasia FNH: A Case Report

FNH is a well-differentiated hepatocyte proliferation without portal spaces or bile ducts [1], which is responsible for a benign hepatic tumor whose prevalence is rare in the general population. There is no risk of malignant transformation because these are polyclonal lesions of a reactive nature [2]. The diagnosis is essentially based on radiology (MRI), and does not require monitoring or treatment in most cases. We report here the case of a patient in whom we made the diagnosis of this benign tumor by an MRI performed in the context of a hepatic mass not individualized by an abdominal ultrasound.

Hemochromatosis-like disease in Brazilian tapirs (Tapirus terrestris) in Pará state, Brazil

ABSTRACT We report two cases of hemochromatosis-like disease in captive Brazilian tapirs, Tapirus terrestris in Pará state, Brazil. Both animals presented symptoms of chronic hepatopathy associated with marked accumulation of hemosiderin. The coloration of Perls demonstrated pronounced iron accumulation in macrophages in the portal space, Kupffer cells, and, to a lesser extent, in the hepatocytes of the periportal region. Marked portal fibrosis was evidenced by Masson’s trichrome. The pathological mechanisms of this disease in tapirs are not yet well established. It has been suggested that the species may have different mechanisms of iron absorption and elimination, rendering them sensitive to elevation in dietary levels of this metal. Two previous reports of this disease in T. terrestris exist from zoos in Australia and Scotland. This is the first report of this disease in tapirs in Brazil based on histopathological and histochemical findings.

In vivo study of anticancer activity of ginsenoside Rh2-containing arginine-reduced graphene in a mouse model of breast cancer.

This study aims to evaluate the in vivo anticancer activity of arginine-reduced graphene (Gr-Arg) and ginsenoside Rh2-containing arginine-reduced graphene (Gr-Arg-Rh2). Thirty-two mice with breast cancer were divided into four groups and treated every three days for 32 days: Group 1, PBS, Group 2, Rh2, Group 3, Gr-Arg, and Group 4, Gr-Arg-Rh2. The tumor size and weight, gene expression (IL10, INF-γ, TGFβ, and FOXP3), and pathological properties of the tumor and normal tissues were assessed. Results showed a significant decrease in TGFβ expression for all drug treatment groups compared with the controls (P=0.04). There was no significant difference among the groups regarding IL10 and FOXP3 gene expression profiles (P>0.05). Gr-Arg-Rh2 significantly inhibited tumor growth (size and weight) compared with Rh2 and control groups. The highest survival rate and the highest percentage of tumor necrosis (87.5%) belonged to the Gr-Arg-Rh2 group. Lungs showed metastasis in the control group. No metastasis was observed in the Gr-Arg-Rh2 group. Gr-Arg-Rh2 showed partial degeneration of hepatocytes and acute cell infiltration in the portal spaces and around the central vein. The Gr-Arg group experienced a moderate infiltration of acute cells into the port spaces and around the central vein. The Rh2 group also showed a mild infiltration of acute and chronic cells in portal spaces. Based on the results, Gr-Arg-Rh2 can reduce tumor size, weight, and growth, TGF-β gene expression, and increase tumor necrosis and survival time in mice with cancer.

Influence of aqueous leafy stem extract of Cochlospermum tinctorium A. Rich. (Cochlospermaceae) on liver injury induced by subacute exposure of rats to carbon tetrachloride

Objectives: Liver disease is a serious public health problem. There are many causes of liver disease and the liver is a vital organ in the body, so when it is damaged, its function can be affected. Cochlospermum tinctorium is a plant commonly used by Central African populations to relieve liver-related ailments such as jaundice and hepatitis. This study aimed to assess the hepatoprotective activity of aqueous leafy stem extract of C. tinctorium against liver injury induced by subacute exposure of rats to carbon tetrachloride (CCl4). Material and Methods: Thirty rats were distributed into six groups including control (H2O), healthy control (H2O), positive control (silymarin 25 mg/kg), extract control (aqueous leafy stem extract 50 mg/kg), and tests (aqueous leafy stem extract 50 or 25 mg/kg). Liver injury was induced by CCl4 (0.5 mL/kg) on the 4th and 11th days of the treatment. Rats were sacrificed on the 15th day, aspartate aminotransferase, alanine aminotransferase (ALT), gamma-glutamyltransferase (γ-GT) activity, and serum levels of total bilirubin, creatinine, and tissue oxidative stress markers (malondialdehyde, glutathione, catalase, and superoxide dismutase) were evaluated. Histological examinations of the liver and kidney were performed. A phytochemical study of C. tinctorium aqueous leafy stem extract was done. Results: This study showed that C. tinctorium aqueous leafy stem extract (50 or 25 mg/kg) significantly reduced (P &lt; 0.01) ALT (94.79 ± 14.99 U/L) and γ-GT (10.08 ± 5.40 U/L) activity, and decreased the serum total bilirubin level compared to control. The aqueous leafy stem extract significantly diminished (P &lt; 0.01) tissue MDA level (2.67 ± 0.05 µmol/mg protein), increased glutathione level (347.08 ± 10.81 nmol/mg protein), catalase (131.03 ± 6.99 µmol/ min/mg protein), and SOD activity (86.0 ±1.50 U/mg). Liver microphotography showed hepatic parenchyma with almost no leukocyte infiltration in the portal and perisinusoidal spaces, and an important reduction of cell necrosis following treatment with the aqueous leafy stem extract compared to the control. Conclusion: These results demonstrate that the hepatoprotective activity of the aqueous leafy stem extract of C. tinctorium may be due to its antioxidant and anti-inflammatory properties and may, therefore, justify the use of this plant as a candidate for complementary study to proceed with the development of medicine against liver diseases.

Numerical mesoscale tissue model of electrochemotherapy in liver based on histological findings

Electrochemotherapy (ECT) and irreversible electroporation (IRE) are being investigated for treatment of hepatic tumours. The liver is a highly heterogeneous organ, permeated with a network of macro- and microvasculature, biliary tracts and connective tissue. The success of ECT and IRE depends on sufficient electric field established in whole target tissue; therefore, tissue heterogeneity may affect the treatment outcome. In this study, we investigate electroporation in the liver using a numerical mesoscale tissue model. We numerically reconstructed four ECT experiments in healthy porcine liver and computed the electric field distribution using our treatment planning framework. We compared the computed results with histopathological changes identified on microscopic images after treatment. The mean electric field threshold that best fitted the zone of coagulation necrosis was 1225 V/cm, while the mean threshold that best fitted the zone of partially damaged liver parenchyma attributed to IRE was 805 V/cm. We evaluated how the liver macro- and microstructures affect the electric field distribution. Our results show that the liver microstructure does not significantly affect the electric field distribution on the level needed for treatment planning. However, major hepatic vessels and portal spaces significantly affect the electric field distribution, and should be considered when planning treatments.

Shining light into the Higgs portal with gamma gamma colliders

High-energy gamma gamma colliders constitute a potential running mode of future lepton colliders such as the ILC and CLIC. We study the sensitivity of a high-energy gamma gamma collider to the Higgs portal scenario to a hidden sector above the invisible Higgs decay threshold. We show that such gamma gamma collisions could allow to probe the existence of dark sectors through the Higgs portal with precision competitive with other planned collider facilities, profiting from the unique combination of sizable cross-section with clean final state and collider environment. In addition, this search could cover the singlet Higgs portal parameter space yielding a first-order electroweak phase transition in the early Universe.

Cystoisospora belli, liver disease and hypothesis on the life cycle.

Cystoisospora belli causes chronic diarrhoea, acalculous cholecystitis, cholangiopathy and disseminated cystoisosporosis in patients with AIDS. Clinical manifestations and histological stages during C. belli infection in a patient with AIDS and liver disease were described. It was possible to identify sporozoite-like structures in the villus epithelium of the duodenum, close to the vascularization that underlies the basal membrane and unizoite tissue cysts near to the vascularization in the lamina propria. Unizoite tissue cysts were found inside of sinusoids in the liver communicating with the central vein and with a bile canaliculus and portal spaces. Based on these findings a hypothesis on C. belli life cycle could consider that the route of migration of unizoite tissue cysts up the liver is via the portal blood. The unizoite tissue cysts located in hepatic portal vein could migrated via sinusoid to central vein and general circulation through the venous system. The unizoite tissue cysts could also return via bile canaliculus to bile duct to portal triad. This hypothesis allows to understand the presence of unizoite stages in blood, the pathway by which the bile ducts become infected and unizoites in the liver being able to behave like hypnozoites that favour relapses and treatment failures.

Does Neutrophil-Lymphocyte Ratio Correlate with the Improvement of Hepatosteatosis after Laparoscopic Sleeve Gastrectomy?

Obesity is a disease that shortens life expectancy and predisposes to many diseases such as severe hepatosteatosis. Hepatosteatosis is characterized by inflammatory infiltration of the portal space. Bariatric surgery has improvement effect on hepatosteatosis and degree of inflammation. Laparoscopic sleeve gastrectomy is an effective and most common therapeutic option for obesity. Neutrophil-lymphocyte ratio is a parameter associated with inflammatory disease. This study aimed to investigate if there is any correlation between improvements in hepatosteatosis and biochemical parameters especially neutrophil-lymphocyte ratio and ultrasonographic findings 1 year after the laparoscopic sleeve gastrectomy. The files of 66 patients who underwent laparoscopic sleeve gastrectomy between May 2017 and April 2020 were retrospectively reviewed. Preoperative and postoperative 1-year demographic data, biochemical and inflammatory parameters, and ultrasonographic reports of the liver were reviewed. A statistically significant improvement in hepatosteatosis was demonstrated by ultrasonography 1 year after laparoscopic sleeve gastrectomy. A significant decrease was also observed in neutrophil-lymphocyte ratio. No correlation was found between the decrease of neutrophil-lymphocyte ratio and improvement in hepatosteatosis. There was also significant difference between the preoperative and postoperative BMI, biochemical and inflammatory parameters. However, we found laparoscopic sleeve gastrectomy is associated with significant improvement in hepatosteatosis and inflammatory parameters; no correlation between the improvement in hepatosteatosis and NLR was seen at 1 year.

Expression of Protein SOX9 in Biliary Atresia.

Biliary atresia (BA) is still an enigmatic disease. Deeper knowledge of its pathophysiology could help develop better treatments. SOX9 regulates bile duct development, liver regeneration and fibrosis; therefore, it could be determinant in characterizing BA liver damage. Aim: To study if there is a SOX9 expression pattern in liver biopsies from BA patients. Liver biopsies from BA patients (group BA), from age-matched infants without primary hepatic disease (group Control), and from patients with other liver conditions (group OLC) were compared. Expression of SOX9 was checked for: amount, intensity of immunoreaction, localization within ductular structures, perifibrotic epithelial cells, and lobular cells. The scores were added to create a scale from 0 to 11 that allowed group comparison. SOX9 Scale and liver survival were also looked for a correlation. All BA cases had a score >4, while all controls scored <4. OLC livers scored 1 to 8 (3.5 ± 2.0) (P < 0.001 between all groups). A cut-off at 4 had 100% sensitivity and 88.24% specificity to differentiate BA from Controls and from OLC (area under receiver operating characteristic curve: 0.9989 (95% confidence interval: 0.9964-1.000). Strong expression of SOX9 was observed mainly in the nuclei of proliferated ductules of portal spaces and fibrotic bridges. SOX9 Scale score could not be related to liver survival in this study. In BA livers, SOX9 is mainly expressed in reactive ductular epithelium, following a pattern significantly different from that seen in non-BA patients; thus, SOX9 Scale may have a role in the diagnosis of BA.

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.