Necroinflammatory Changes Research Articles

Takayasu Arteritis with medio-medial intussusception?

We present an autopsy case of a child with Takayasu arteritis who succumbed due to cerebrovascular accident with an interesting finding in the inflamed aorta. On account of necro-inflammatory changes in the media of the distal descending thoracic aorta coupled with the shear stress of accelerated hypertension, there was a medial detachment, which migrated and lay between the intima and media of the abdominal aorta. This displacement was visualized on gross and histopathological examination as a ‘laminated’ appearance of coils of discontinuous inflamed tunica media, reminiscent of a hydatid cyst, which has been designated as medio-medial intussusceptions.

Detection of SARS-CoV-2 Viral Genome and Viral Nucleocapsid in Various Organs and Systems.

While considerable attention has been devoted to respiratory manifestations, such as pneumonia and acute respiratory distress syndrome (ARDS), emerging evidence underlines the significance of extrapulmonary involvement. In this study, we examined 15 hospitalized patients who succumbed to severe complications following SARS-CoV-2 infection. These patients were admitted to the Sibiu County Clinical Emergency Hospital in Sibiu, Romania, between March and October 2021. All patients were ethnic Romanians. Conducted within a COVID-19-restricted environment and adhering to national safety protocols, autopsies provided a comprehensive understanding of the disease's multisystemic impact. Detailed macroscopic evaluations and histopathological analyses of myocardial, renal, hepatic, splenic, and gastrointestinal tissues were performed. Additionally, reverse transcription-quantitative polymerase chain reaction (rt-qPCR) assays and immunohistochemical staining were employed to detect the viral genome and nucleocapsid within the tissues. Myocardial lesions, including ischemic microstructural changes and inflammatory infiltrates, were prevalent, indicative of COVID-19's cardiac implications, while renal pathology revealed the chronic alterations, acute tubular necrosis, and inflammatory infiltrates most evident. Hepatic examination identified hepatocellular necroinflammatory changes and hepatocytic cytopathy, highlighting the hepatic involvement of SARS-CoV-2 infection. Splenic parenchymal disorganization was prominent, indicating systemic immune dysregulation. Furthermore, gastrointestinal examinations unveiled nonspecific changes. Molecular analyses detected viral genes in various organs, with immunohistochemical assays confirming viral presence predominantly in macrophages and fibroblasts. These findings highlighted the systemic nature of SARS-CoV-2 infection, emphasizing the need for comprehensive clinical management strategies and targeted therapeutic approaches beyond respiratory systems.

Immune system dysregulation in the pathogenesis of non-alcoholic steatohepatitis: unveiling the critical role of T and B lymphocytes.

Non-alcoholic fatty liver disease (NAFLD), characterized by the excessive accumulation of fat within the cytoplasm of hepatocytes (exceeding 5% of liver weight) in individuals without significant alcohol consumption, has rapidly evolved into a pressing global health issue, affecting approximately 25% of the world population. This condition, closely associated with obesity, type 2 diabetes, and the metabolic syndrome, encompasses a spectrum of liver disorders ranging from simple steatosis without inflammation to non-alcoholic steatohepatitis (NASH) and cirrhotic liver disease. Recent research has illuminated the complex interplay between metabolic and immune responses in the pathogenesis of NASH, underscoring the critical role played by T and B lymphocytes. These immune cells not only contribute to necroinflammatory changes in hepatic lobules but may also drive the onset and progression of liver fibrosis. This narrative review aims to provide a comprehensive exploration of the effector mechanisms employed by T cells, B cells, and their respective subpopulations in the pathogenesis of NASH. Understanding the immunological complexity of NASH holds profound implications for the development of targeted immunotherapeutic strategies to combat this increasingly prevalent and burdensome metabolic liver disease.

Impact of Direct Acting Antiviral (DAA) Agents on Hematological and Hepatic Statuses of Patients with Chronic Hemolytic Anemias and Chronically Infected with Hepatitis C Virus (HCV)

Abstract Background Different combinations of Direct Antiviral Agents (DAAs) have been used against different Hepatitis C Virus (HCV) genotypes and in different types of patients. Aim and objectives To investigate the impact of DAA-based regimens on hematological and hepatic statuses of patients with chronic hemolytic anemias and chronically infected with HCV. Subjects and Methods This is a cross sectional study, was carried out at viral hepatitis research and treatment center of Ain Shams University Hospitals, on 50 patients with chronic hemolytic anemias and has HCV infection, from December 2019 till June 2020. Result There was high statistically significant difference before treatment, first month, third month and sixth month follow up in chronic liver disease group as regard HGB, statistically significant in Hemolytic anemia group (no splenectomy) as regard HGB and there was high statistically significant difference between the studied groups as regard HGB. Conclusion DAAs therapy is effective and tolerable in patients with chronic HCV patients. It improves liver necro-inflammatory changes in patients, evidenced by decreased liver enzymes' level, but still require careful observation during DAAs therapy for being more susceptible for hemolytic anemia.

The Potential Protective Role of Naringenin against Dasatinib-Induced Hepatotoxicity.

Dasatinib (DASA) is a novel tyrosine kinase inhibitor, approved for leukemia treatment. However, the long-term use of DASA induces several complications, especially liver damage. On the other hand, Naringenin (NGN) is a potent antioxidant and anti-inflammatory agent which is known to exert protective effects in several liver disease animal models. Yet, the effect of NGN on DASA-induced hepatotoxicity has not been examined. This study investigated the hepatoprotective effects of NGN against DASA-induced acute liver injury, using a mouse model. The mice were given NGN (50, 100, and 200 mg/kg po) or saline for 7 days, followed by DASA on the eighth day (25 mg/kg p.o.). DASA treatment alone was found to cause overexpression of proinflammatory cytokines, such as interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), and malonyl aldehyde (MDA), whereas attenuation of antioxidant genes including superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and glutathione peroxidase (GPx). Interestingly, a pretreatment with NGN + DASA resulted in minimizing the proinflammatory mediators and restoring the levels of antioxidant genes. In addition, there was evidence of necro-inflammatory changes in histopathological findings in the liver samples after DASA administration which remarkably reduced with NGN + DASA. Thus, this study revealed that NGN could minimize the hepatotoxicity induced by DASA by providing anti-inflammatory and antioxidant protection.

Oncogenic challenge of bromocriptine and L-arginine versus conventional antidiabetics on diethyl nitrosamine-induced liver tumorigenesis in diabetic rats: focus on AMPK activation

Background: Diabetes mellitus (DM) is associated with a spectrum of cancers where the metabolic antecedents, consequences, and therapy might affect cancer risk. The association between hepatocellular carcinoma (HCC) and DM had been confirmed. Approaches to HCC prevention focus on the molecular regulators of the disease process defined as the inflammation-fibrosis-cancer axis. The AMP-activated protein kinase (AMPK) is an interesting metabolic tumor suppressor and a promising target for cancer prevention and therapy. This study aimed to investigate the effects of bromocriptine mesylate and L-arginine on hepatic carcinogenesis on a rat model of hepatic neoplasia induced by diethyl nitrosamine (DENA) and promoted by type-2 DM in contrast to the conventional antidiabetics.Methods: One hundred male Wistar rats were randomly assigned into two sets; control set (normal, HCC, DM, and combined HCC/DM) and treated set where rats received one of the following drugs for another 5 weeks: insulin glargine, glimepiride, metformin, pioglitazone, bromocriptine mesylate, or L-arginine. Bodyweight changes, blood glucose level, liver functions tests, serum C-peptide and alpha-fetoprotein (AFP), and hepatic activated AMPK were assessed beside the hepatic histopathological changes.Results: Equivalent to metformin, bromocriptine and L-arginine treatment significantly reduced AFP, despite their minor glycemic control. L-arginine induced AMPK activation, yet less than metformin. Histopathologic examination revealed a reduction in hepatic intra-lobular chronic inflammatory cell infiltration, steatosis and necrosis by metformin, bromocriptine, and L-arginine. Hepatic necro-inflammatory changes were most prominent in insulin-treated rats.Conclusions: L-arginine and bromocriptine mesylate prevent early neoplastic changes almost equivalent to metformin at least partially via hepatic AMPK activation.

S3170 Syphilitic Hepatitis With Cholestatic Liver Injury

Introduction: The incidence of syphilis in the United States has increased, predominantly among men who have sex with men. Very few patients with early syphilis meet the criteria for syphilitic hepatitis, but many are HIV+ and engage in high-risk sexual behavior. Case Description/Methods: A 30-year-old man who identified as a MSM presented with yellowing of his eyes and hyperbilirubinemia, preceded by one month with a rash and photosensitivity and redness of his right eye. He denied any penile lesions, history of liver disease or alcohol use. A physical examination revealed multiple hyperpigmented macular lesions over his torso, arms, palms, and the soles of his feet and scleral icterus. A slit lamp examination indicated anterior uveitis in both eyes and chorioretinitis/placoid retinitis in the right eye. CBC and iron studies showed mild anemia of chronic disease (Hb 11.7 g/dL). BMP was within normal limits. LFTs were as mentioned in Table 1. Blood tests showed positive HBsAb and T. pallidum antibody with RPR 1:128. Serum markers for viral hepatitis and HIV were negative. CSF from a lumbar puncture had an elevated WBC count (9/mm3). No biliary obstruction or masses were noted during on US and MRCP. Liver biopsy showed bland perivenular cholestasis (zone 3) (Fig. 1A) without necroinflammatory changes, mild to minimal portal inflammation (Fig. 1B), bile duct damage, and ductular reaction. The patient was treated with penicillin G for neurosyphilis, prednisolone and cyclopentolate for ocular syphilis, and ursodiol for cholestasis. Total bilirubin levels decreased to 1.7 mg/dL after 8 weeks of follow-up, and liver enzymes normalized. Discussion: This patient met the criteria for syphilitic hepatitis (elevated liver enzymes, serologic evidence of syphilis, exclusion of other etiology, and improvement following appropriate therapy). He also had bilateral anterior uveitis and placoid retinitis of the right eye, suggesting ocular syphilis. Serum chemistries, testing for T. pallidum and other serologies (including positive anti-smooth muscle antibody) supported hepatic involvement, and CSF studies were consistent with neurosyphilis. Liver biopsy showed a bland cholestatic pattern without evidence of other causes of liver disease. The biopsy results are compatible with syphilitic hepatitis, though histologic features can vary and direct staining for spirochetes has limited sensitivity. These findings, together with his rapid improvement with penicillin therapy, confirmed a diagnosis of syphilitic hepatitis.Figure 1.: (A) Liver specimen (x40 magnification, hematoxylin and eosin stain) showing bland perivenular cholestasis (zone 3 with rare apoptotic hepatocytes. No necroinflammatory activity is present. (B) Liver specimen (x40 magnification, hematoxylin and eosin stain) showing periportal inflammation and bile duct damage with mild bile ductular reaction. Table 1. - Liver function test results AST 41 IU/L ↑ (ULN < 38 IU/L) ALT 53 IU/L ↑ (ULN < 42 IU/L) ALP 210 IU/L ↑↑ (ULN < 129 IU/L) Total bilirubin 11.6 mg/dL ↑↑ (ULN < 1.3 mg/dL) Direct bilirubin 8.8 mg/dL ↑↑ (ULN < 0.4 mg/dL) GGT 53 (ULN < 61 IU/L) Albumin 3.8 g/dL INR 1.0 AST, aspartate transaminase; ALT, alanine transaminase; ALP, alkaline phosphatase; GGT, gamma-glutamyl transferase; INR, international normalized ratio; UNL, upper limits of normal.

Diacerein counteracts acetaminophen-induced hepatotoxicity in mice via targeting NLRP3/caspase-1/IL-1\u03b2 and IL-4/MCP-1 signaling pathways

The current study aims at repurposing the anti-arthritic drug diacerein (DCN) for the treatment of acetaminophen hepatotoxicity and investigating the potential underlying mechanisms. Mice were randomly divided into six groups receiving either no treatment (control group), 20 mg/kg DCN i.p, 400 mg/kg acetaminophen i.p, DCN 4 h before acetaminophen, DCN 2 h after acetaminophen, or 400 mg/kg N-acetylcysteine (NAC) i.p, 2 h after acetaminophen. Biomarkers of liver dysfunction, oxidative stress, and apoptosis were assessed. Hepatic necroinflammatory changes were evaluated along with hepatic expression of NF-κB and caspase-1. The levels of NLRP3, IL-1β, IL-4, MCP-1, and TNF-α in the liver, as well as CYP2E1 mRNA expression, were measured. Diacerein significantly reduced biomarkers of liver dysfunction, oxidative stress, hepatocyte necrosis, and infiltration of neutrophils and macrophages whether administered 4 h before or 2 h after acetaminophen. Further, the effects were comparable to those of NAC. Diacerein also counteracted acetaminophen-induced hepatocellular apoptosis by increasing Bcl-2 and decreasing Bax and caspase-3 expression levels. Moreover, DCN normalized hepatic TNF-α and significantly decreased NF-κB p65 expression. Accordingly, DCN can prevent or reverse acetaminophen hepatotoxicity in mice, suggesting potential utility as a repurposed drug for clinical treatment.

Evidence-Based Care Can Improve Treatment Compliance and Quality of Life of Patients with Acute Pancreatitis.

Acute pancreatitis represents a disease characterized by acute necro-inflammatory changes in the pancreas, which is histologically characterized by destruction of alveolar cells. We aim to explore whether evidence-based care can improve treatment compliance and quality of life of patients with acute pancreatitis. The changes of hemoglobin (HGB), serum pre-albumin (PAB), and serum albumin (ALB) before and after care were observed, as well as the incidence of complications after care, total effective rate after care, disease severity (bedside index for severity in acute pancreatitis, BISAP) before and after care, and psychological scores of the two groups before and after care were observed. Patients' compliance after care, self-management scores after care, and quality of life after care were compared between the two groups. After care, HGB, PAB, and ALB increased significantly in both groups (p < 0.05) and were higher in OG than CG. Compared with CG, OG had significantly lower incidence of complications (p=0.009), significantly higher total effective rate (p=0.011), significantly lower disease severity (p < 0.05), significantly better psychological condition scores (p < 0.05), significantly higher compliance scores (p < 0.05), higher self-management scores (p < 0.05), and significantly higher quality of life (p < 0.001). Evidence-based care can improve treatment compliance of patients with acute pancreatitis and can effectively improve their quality of life.

Efficacy of Five Organic Acids Combination on T2- Mycotoxicosis in Rats

Mycotoxins are secondary by-products of mold metabolism and are accountable for human and animal mycotoxicosis. The most serious trichothecenic mycotoxin is the fungal T-2 mycotoxin. T-2 mycotoxin impaired nutrient absorption, metabolism, and then, eliciting severe oxidoreductive stress. Diet plays a key role beyond the supply of nutrients in order to promote animal and human health. Organic acids have been commonly used to exert antioxidative stress capacity in the liver and gut ecosystem. This study is planned to explore, the competence of using (X-MoldCid®) during chronic T-2 mycotoxicosis course in rat. Rats were allocated into 4 main groups, (CN-Gr), negative control and was allowed for the free access to the normal rats chow and the tap water for 90 days. (OAC-Gr), which was assigned as the organic acids positive control and was allowed for the free access to normal rat chow and (X-MoldCid®) in the tap water for 90 days .Group 3 or (T2-Gr) and was given the T2 contaminated chow ad libitum and group 4 (T2+OAC-Gr) .Each one of the four groups was subdivided into two subgroups (n=7) that one was sacrificed on day 45 (Subgroup A) meantime the remaining rats (Subgroup B) maintained until finishing of the entire study period (90 days). In T2 intoxicated group, liver histopathological findings revealed, lesions of reversible types (hydropic and fatty degenerations) while intestinal histopathological findings revealed, lesions of hyperactive goblet cells with sever slaughing of epithelia. In T2+OAC-Gr, the ultimate efficacy of organic acids success in limiting the apoptotic activity and preventing hepatic necroinflammatory changes which were in accordance with the improvement of antioxidative status, liver and intestinal function enzymes and other serum biochemical estimated tests. The total results of this study have been clarified the regenerative and antioxidant potentials of (X-MoldCid®) in coping with T2-toxin mediated intestinal lesions and hepatotoxicityin rats.

Disparities in hepatic copper concentrations determined by atomic absorption spectroscopy, inductively coupled plasma mass spectrometry, and digital image analysis of rhodanine-stained sections in dogs.

To investigate disparities in hepatic copper concentrations determined by atomic absorption spectroscopy (AAS), inductively coupled plasma mass spectrometry (ICP-MS), and digital image analysis of rhodanine-stained sections. 516 dogs. Medical records of dogs for which hepatic biopsy specimens had been submitted between January 1999 and December 2019 for evaluation of copper content were reviewed. Paired hepatic copper concentrations obtained with digital image analysis and AAS or ICP-MS were compared, and Spearman rank correlation coefficients were calculated to test for correlations between qualitative copper accumulation scores and hepatic copper concentrations. For dogs for which ≥ 4 rhodanine-stained hepatic sections were available, intraindividual variation in copper distribution across hepatic sections was evaluated. Median hepatic copper concentrations obtained with digital image analysis exceeded concentrations obtained with AAS or ICP-MS. Concentrations were also higher in older dogs (≥ 9 years vs < 9 years), dogs of breeds with a typical body weight ≥ 20 kg (44 lb), and dogs with necroinflammatory changes or uneven copper distribution. Qualitative copper accumulation scores were significantly associated with hepatic copper concentrations; however, the correlation between qualitative score and concentration obtained with digital image analysis (rs = 0.94) was higher than the correlation between qualitative score and concentration obtained with AAS (rs = 0.75) or ICP-MS (rs = 0.57). The coefficient of variation for hepatic copper concentrations obtained with digital image analysis was significantly higher for dogs with higher hepatic copper concentrations. Results suggested that spectroscopic-spectrometric analysis of hepatic biopsy specimens commonly underestimated the concentration obtained by digital image analysis of rhodanine-stained sections.

HISTOMORPHOLOGICAL EFFECTS OF SALICYLIDENE SALICYL HYDRAZIDE ON LIVER IN SPRAGUE DAWLEY RATS

Objective: This study was aim to identify histomorphological changes in the liver of Sprague dawley rats after exposure to Saliyclidene salicylhydrazide and dose dependent histomorphological changes in the liver. Materials and Methods: This study was started from Mar 2019, to June 2019. In this study, acute toxicity of seven days, the sixteen Sprague dawley female rats were selected. They were divided into four groups. Two test groups (A &amp; B). Group A was given 25mg/kg SCS, while in group B 50mg/kg of SCS was given. Positive control group (C) was given paracetamol 300mg/kg. Group D was a negative control group. Each group had four animals. After seven days of exposure to SCS through oral route all the animals were euthanized. Their livers were harvested and processed for preparation of histological slides. These slides were then analyzed by microscopy and histomorphological changes were recorded and analyzed according to Roenigk classification system. Results: Necroinflammatory changes were observed in Group A, B and C compared to Group D(-control). However, difference between Group A and B was not significant. Nuclear pleomorphism was observed in hepatocytes of Group A, B and C compared to group D(control). Pleomorphic changes in the intervention group A &amp; B were same. Steatosis was observed in group A, B and C compared to Group D. Steatosis in group A and B were same while in group C it was relatively more significant. The overall grading according to ROENIGK classification system showed significantly higher toxicity in group B, compared to other intervention groups (A, B, C) and control group D. Conclusion: Significant effects of SCS were observed in liver of Sprague dawley rats, however, the toxic effects were less severe. Liver Parenchyma and architecture were preserved.

Synbiotic (PoultryStar® Sol) Protects Rat Liver from Oxidoreductive Stress Induced by T2-Mycotoxicity

Mycotoxins are secondary metabolic byproducts of molds that posses harmful and detrimental impact on animal and human health. Fungal T2 mycotoxin is the most efficacious trichothecene mycotoxin. It can induce hepatic and intestinal damages through eliciting severe oxidoreductive stress. Consequently, dysbiosis (alteration in the compositional balance of intestinal microbiota) occurred that can play an important role in the pathogenesis of several liver diseases. Recently, the using of pro and prebiotics was proven to exert antioxidative stress potentials in liver and gut ecosystem. To explore, the efficacy of using synbiotic (PoultryStar® Sol) during chronic T-2 mycotoxicosis course in rat, this study was designed. Rats were allocated into 4 main groups, (CN-Gr), which was treated as the negative control and was allowed for the free access to the normal rats chow and the tap water for 90 days, (PSS-Gr), which was assigned as the synbiotic positive control group and was allowed for the free access to normal rat chow and (PoultryStar® Sol) in the tap water (20mg/rat every 5 days) for 90 days. Group 3 or (T2-Gr) and was given the T2 contaminated chow ad libitumat a level of (470 ppb) along with normal drinking water for 90 days, and Group 4 (T2+PSS-Gr) which was given the T-2 contaminated chow ad libitumat the same level of Group 3 along with synbiotic (PoultryStar® Sol) in the tap water the same dose of (PSS-Gr) for 90 days. Each one of the four groups was subdivided into two subgroups (n=7) that one was exsanguinated on day 45 (Subgroup A) meantime the remaining rats (Subgroup B) were kept until the end of the entire study period (90 days). In T2 intoxicated group, liver histopathological findings on day 45 revealed lesions of reversible types (hydropic and fatty degenerations) only. Concurrently, on day 90 the changes comprised apoptosis and some necroinflammatory lesions. In T2+PSS-Gr, the ultimate efficacy of synbiotic success in preventing hepatic necroinflammatory changes and limiting the apoptotic activity which were in accordance with the amelioration of antioxidative status, liver function enzymes and other serum biochemical estimated tests. Summing up, the total results of this study has been clarify the regenerative and antioxidant potentials of (PoultryStar® Sol) in coping with T2 toxin mediated hepatotoxicity in rats.

Hepatitis E Virus after Heart Transplantation, Single Center Experience

Purpose Hepatitis E virus (HEV) infection can cause chronic hepatitis and can lead to liver cirrhosis and liver failure in patients after solid organ transplantation. However, there is no approved therapy of HEV infection so far. Methods We present three patients after heart transplantation (HTx) with confirmed HEV virus replication at various stages of the disease who were successfully treated with ribavirin monotherapy. Results 62-year old man after HTx in 2/2012 for advanced heart failure due to ischemic cardiomyopathy had had long-term elevated aminotransferases due to right ventricle failure with ascites. During the first year after HTx, ALT and GMT increased significantly despite circulatory compensation. Ascites reappeared and portal hypertension was confirmed with hepatic venous pressure gradient of 18 mmHg and oesophageal varices. Necroinflammatory changes in liver biopsy samples were found. HEV infection was confirmed by HEV RNA positivity in the blood. Due to the long-term course and the findings described, HEV infection was classified as chronic. After six months of therapy with ribavirin, ALT levels normalized and small oesophageal varices regressed. HEV RNA remained negative 6 month after the end of therapy, the patient achieved sustained virological response (SVR). The patient is still alive in good clinical condition. In the second patient, 69-year old man, laparoscopic cholecystectomy (CHCE) for cholecystitis was performed two years after HTx. Abdominal discomfort persisted for three months after CHCE together with ALT elevation. HEV infection was confirmed by HEV RNA positivity. The patient achieved SVR as well with 4 months of ribavirin therapy. In the third patient, 44-year old man, who presented with slightly elevated liver enzymes levels, acute HEV infection was diagnosed 3 years after HTx. After 4 months of ribavirin therapy, ALT became normal and the patient achieved SVR. Conclusion In solid organ transplant recipient, HEV infection may take a chronic course with rapid progression of liver disease despite minimal clinical symptoms. It is necessary to think of the diagnosis because ribavirin therapy is higly effective and may prevent progression of liver fibrosis.

Antioxidant Defense, Oxidative Modification, and Salivary Gland Function in an Early Phase of Cerulein Pancreatitis

Acute pancreatitis (AP) is a multifactorial disease characterized by necroinflammatory changes of the pancreas. Our study is the first study which evaluated the relationship between the free radical production, enzymatic and nonenzymatic antioxidants, oxidative damage, and secretory function of the salivary glands of AP rats. Male Wistar rats were divided equally into 2 groups: control (n = 9) and AP (n = 9). AP was induced by intraperitoneal injection with cerulein and confirmed by higher serum amylase and lipase. We have demonstrated that the superoxide dismutase and glutathione reductase activities, as well as reduced glutathione concentration, were significantly decreased in both the parotid and submandibular glands of AP rats as compared to the control rats. The production of free radicals evidenced as dichlorodihydrofluorescein assay and the activity of NADPH oxidase and xanthine oxidase and IL-1β concentration were significantly higher in the parotid and submandibular glands of AP rats compared to the controls. In AP rats, we also showed a statistical increase in oxidation modification products (advanced glycation end products and advanced oxidation protein products), salivary amylase activity, and significant decrease in the total protein content. However, we did not show apoptosis and any morphological changes in the histological examination of the salivary glands of AP rats. To sum up, cerulein-induced AP intensifies production of oxygen free radicals, impairs the redox balance of the salivary glands, and is responsible for higher oxidative damage to these glands. Interestingly, oxidative modification of proteins and dysfunction of the antioxidant barrier are more pronounced in the submandibular glands of AP rats.

Liver Fibrosis Helps to Distinguish Autoimmune Hepatitis from DILI with Autoimmune Features: A Review of Twenty Cases.

Background and Aims: Drug-induced liver injury with autoimmune features (AI-DILI) mimics the clinical presentation, and laboratory and pathologic features of idiopathic autoimmune hepatitis (AIH). We aimed to identify histopathologic hallmarks to differentiate these entities.Methods: All liver biopsies archived for the past 10 years were reviewed retrospectively to identify cases of recently detected liver injury associated with predominantly lymphoplasmacytic interphase hepatitis, positive markers for liver autoimmunity, and negative tests for viral hepatitis. Twenty cases were divided into AIH (n = 12) or AI-DILI (n = 8) groups. Blind qualitative evaluation of necroinflammatory changes and liver fibrosis were performed according to the Scheuer scoring system. Cellular densities were determined using ImageJ (V1.51t, National Institutes of Health, Bethesda, MD, USA). Fibrosis was assessed on Masson trichrome-stained slides, and collagen deposition was estimated following a protocol of color deconvolution.Results: Necroinflammatory changes as well as densities (portal and lobular) of neutrophils and eosinophils, intracellular cholestasis, and regenerative changes did not differ between the two groups (P ≥ 0.05). Neutrophil densities but not eosinophils showed a positive correlation with the severity of hepatocellular damage (r = 0.6 and 0.58, vs. alanine aminotransferase, P < 0.05). Ceroid-laden macrophages but not histiocytic aggregates appeared to be more common in AI-DILI (P < 0.05). AIH patients presented more often with evidence of chronic damage, including higher scores of fibrosis and collagen deposition, in comparison to AI-DILI (P < 0.05).Conclusions: Although there is no histologic feature pathognomonic for AI-DILI or AIH, advanced stages of liver fibrosis can be used to support the diagnosis of AIH in some cases. Definitive diagnosis of AI-DILI requires follow-up and demonstration of complete remission after drug withdrawal with no need for immunosuppression.

Impact of omega-3 fatty acids on evolution of carbon tetrachloride- (CCl4) induced liver cirrhosis in mice : A histological and immunohistochemical study

hepatic architecture. Omega-3 polyunsaturated fatty acids are common antioxidant, anti-inflammatory and anti-fibrotic agentsAim: This study was conducted to investigate the potential effects of omega-3 fatty acids on experimentally induced cirrhosis.Materials and Methods: 60 animals were divided into three groups: Group I (control): 10 animals, group II: 25 animals treated with carbon tetrachloride (CCl4), and Group III : 25 animals treated with CCl4 then with omega-3 concomitant with CCl4 for additional two weeks after induction of cirrhosis. Body weight and liver weight coefficient were measured. Liver samples were taken for histological and immunohistochemical studies.Results: Omega-3 fatty acids treatment attenuated the CCl4 induced cirrhosis. Histological studies revealed that it decreased the stage of fibrosis, and the grade of the necroinflammatory changes. Immunohistochemical studies demonstrated that apoptotic changes diminished in cirrhotic livers after treatment with omega-3 fatty acids with a significant decrease in the cleaved caspase-3 index. Furthermore, there was a significant decrease in the number of macrophages, and hepatic stellate cells activation.Conclusion: Our results suggest that omega-3 fatty acids have an anti-inflammatory and anti-fibrotic effects on CCl4 induced liver cirrhosis in mice.

Mechanisms and Management of Acute Pancreatitis

Acute pancreatitis represents a disorder characterized by acute necroinflammatory changes of the pancreas and is histologically characterized by acinar cell destruction. Diagnosed clinically with the Revised Atlanta Criteria, and with alcohol and cholelithiasis/choledocholithiasis as the two most prominent antecedents, acute pancreatitis ranks first amongst gastrointestinal diagnoses requiring admission and 21st amongst all diagnoses requiring hospitalization with estimated costs approximating 2.6 billion dollars annually. Complications arising from acute pancreatitis follow a progression from pancreatic/peripancreatic fluid collections to pseudocysts and from pancreatic/peripancreatic necrosis to walled-off necrosis that typically occur over the course of a 4-week interval. Treatment relies heavily on fluid resuscitation and nutrition with advanced endoscopic techniques and cholecystectomy utilized in the setting of gallstone pancreatitis. When necessity dictates a drainage procedure (persistent abdominal pain, gastric or duodenal outlet obstruction, biliary obstruction, and infection), an endoscopic ultrasound with advanced endoscopic techniques and technology rather than surgical intervention is increasingly being utilized to manage symptomatic pseudocysts and walled-off pancreatic necrosis by performing a cystogastrostomy.

A Case of Upper Gastrointestinal Bleeding Due to a Large Gastric Lipoma Within a Hiatal Hernia

Gastric lipomas are rare mesenchymal tumors with a prevalence of 0.03-0.18% in the general population. They account for 5% of gastrointestinal tract lipomas and represent 3% of benign gastric tumors. They are usually asymptomatic, but can cause symptoms of abdominal discomfort, obstruction, intussusception, or bleeding. Most gastric lipomas (75%) are located in the antrum. We present a case of a large, proximal lesser curvature gastric lipoma contained within a hiatal hernia that presented as an upper gastrointestinal hemorrhage. A 78 female with a remote history of stroke on clopidogrel was admitted after two days of melena. She was hemodynamically stable with mild tachycardia. Melena was preceded by two days of mid-epigastric discomfort. She endorsed rare use of aspirin for headaches. Hemoglobin dropped from baseline of 14 gm/dL to 6.8 gm/dL requiring transfusion. Upper endoscopy revealed a 4-5 cm, smooth, soft, submucosal mass on the proximal lesser curvature of the stomach with a 1 cm clean based ulcer overlying the mass. The mass was located within a large hiatal hernia. Mucosal biopsies obtained during the procedure showed fundic type mucosa with active gastritis, necroinflammatory changes, and were negative for Helicobacter pylori. A CT scan of the chest, abdomen, and pelvis showed a lipomatous, lower mediastinal mass within a hiatal hernia measuring 11.5 x 9.4 x 8.2 cm concerning for gastric lipoma versus low grade liposarcoma. The patient underwent laparoscopic mobilization of a large Type III hiatal hernia with conversion to open for subsequent wedge resection of the gastric mass and hiatal hernia repair. Pathologic examination revealed a well-differentiated, mature, encapsulated, fatty neoplasm consistent with gastric lipoma with necrosis and ulceration of the overlying gastric mucosa. MDM2 gene amplification was not detected, confirming the diagnosis of benign lipoma. The patient had an uneventful recovery and is doing well post-operatively. While gastric lipomas harbor no malignant potential, they should be treated when they present with complications. Traditionally, symptomatic gastric lipomas are managed with surgical resection or enucleation. Endoscopic resection and submucosal dissection have been used to manage these tumors, but these techniques are technically challenging and carry an increased risk of perforation with larger masses.Figure: Axial CT scan image showing the large lipomatous mass in the lower mediastinum within a hiatal hernia.Figure: Large submucosal mass with overlying clean based ulcer as seen on retroflexion during endoscopy.Figure: Endoscopic image of submucosal mass and ulcer appreciated along the proximal lesser curvature with the diaphragmatic hiatus seen in the background.

TLR9 is up-regulated in human and murine NASH: pivotal role in inflammatory recruitment and cell survival.

Our novel clinical data and studies in overnutrition models, including those with diabetes and metabolic syndrome, clarify TLR9 as a pro-inflammatory trigger in NASH. This response is mediated via M1-macrophages and neutrophil chemotaxis.