Necrotic Foci Research Articles

Infiltrative multifocal glioblastoma progression in a twelve-year-old boy after COVID-19 infection: a case report

Background: Glioblastoma is one of the most malignant types of primary central nervous system tumors with a high recurrence rate and dismal prognosis. Multifocal glioblastoma has been shown to have a poorer prognosis than solitary glioblastoma. Cancer patients are at risk of contracting COVID-19. It is hypothesized that COVID-19 may induce glioma tumorigenesis via angiotensin enzyme 2 receptor. We reported a rare pediatric multifocal glioblastoma in a twelve-year-old boy complicated with COVID-19. Case Presentation: The patient was a twelve-year-old boy with a new-onset unprovoked seizure and headache. Magnetic resonance imaging (MRI) showed a heterogeneous solid cystic mass in the left temporal region (2.1x2.1x2.8 cm) with an increased choline/creatinine ratio and choline/n-acetyl acetate aspartate (NAA) ratio suggestive for high-grade glioma. The patient was contracting COVID-19 shortly after the diagnosis of glioblastoma. Two weeks later, patients came with significant neurological deterioration, hemiparesis, headache, and vomiting. MRI showed an infiltrative mass in the temporal and parietal region (5.05x8.03x8.3 cm) with intratumoral hemorrhage, also causing midline shift deviation (11.9 mm). The patient underwent trepanation and total safe resection of the tumor. Histopathological findings showed neoplastic cells with abundant mitotic figures, necrotic foci and pseudopalisading necrosis. These findings confirmed the diagnosis of multifocal glioblastoma. Conclusion: Glioblastoma is a rare disease in the pediatric population with a poor prognosis due to its infiltrative nature and high recurrence rate. The patient had an acute deterioration of the neurological condition and rapid growth of the tumor after he contracted COVID-19, which may or may not be incidental. Further observation of similar cases will be required to determine the association between glioblastoma and COVID-19.

Hepatoprotective activity of Amalakyadi Gana, a polyherbal ayurvedic formulation in paracetamol-induced hepatotoxicity in mice

Since ancient times, Amalakyadi Gana, a polyherbal formulation of Susruta Samhita (6th century BCE), has been used for the prevention and treatment of numerous gastrointestinal diseases. This formulation consists of fruits of Phyllanthus emblica, Terminalia chebula, Piper longum, and the root of Plumbago zeylanica. The hepatoprotective efficacy of this formulation was evaluated following the acute toxicity study in mice to validate its ayurvedic uses. The hepatoprotective efficacy was assessed using paracetamol-induced hepatotoxicity in Swiss albino mice. Research drug exhibited in normalizing the PCM-dependent rise of serum liver function markers. After administration of the aqueous extract of Amalakyadi Gana, relevant blood biochemical measures showed significant (P < 0.05) hepatoprotective activity in a dosage-dependent manner, especially at the dose of 700 mg/kg orally in mice. When compared to the control group, significant (p < 0.05) histological alterations were also observed in the liver tissues. This formulation exhibited results in normalizing the liver architecture by decreasing necrotic foci along with the normal liver parenchymal structure in the research drug pre-treated groups mainly at the dose of 700 mg/kg, caused due to paracetamol toxicity. The research drug's sustained activity was comparable to that of the silymarin (200 mg/kg, p.o.) reference medicine. This formulation possesses significant hepatoprotective activity without any toxicity in mice.

Pathology and Pathogenesis of Brain Lesions Produced by Clostridium perfringens Type D Epsilon Toxin.

Clostridium perfringens type D epsilon toxin (ETX) produces severe, and frequently fatal, neurologic disease in ruminant livestock. The disorder is of worldwide distribution and, although vaccination has reduced its prevalence, ETX still causes substantial economic loss in livestock enterprises. The toxin is produced in the intestine as a relatively inactive prototoxin, which is subsequently fully enzymatically activated to ETX. When changed conditions in the intestinal milieu, particularly starch overload, favor rapid proliferation of this clostridial bacterium, large amounts of ETX can be elaborated. When sufficient toxin is absorbed from the intestine into the systemic circulation and reaches the brain, two neurologic syndromes can develop from this enterotoxemia. If the brain is exposed to large amounts of ETX, the lesions are fundamentally vasculocentric. The neurotoxin binds to microvascular endothelial receptors and other brain cells, the resulting damage causing increased vascular permeability and extravasation of plasma protein and abundant fluid into the brain parenchyma. While plasma protein, particularly albumin, pools largely perivascularly, the vasogenic edema becomes widely distributed in the brain, leading to a marked rise in intracranial pressure, coma, sometimes cerebellar herniation, and, eventually, often death. When smaller quantities of ETX are absorbed into the bloodstream, or livestock are partially immune, a more protracted clinical course ensues. The resulting brain injury is characterized by bilaterally symmetrical necrotic foci in certain selectively vulnerable neuroanatomic sites, termed focal symmetrical encephalomalacia. ETX has also been internationally listed as a potential bioterrorism agent. Although there are no confirmed human cases of ETX intoxication, the relatively wide species susceptibility to this toxin and its high toxicity mean it is likely that human populations would also be vulnerable to its neurotoxic actions. While the pathogenesis of ETX toxicity in the brain is incompletely understood, the putative mechanisms involved in neural lesion development are discussed.

Primary retroperitoneal perirenal CIC rearrangement sarcoma: A case report.

Primary retroperitoneal perirenal CIC rearrangement sarcoma is rare. The current case report presents a 69-year-old male patient with this pathology, including the clinical features, pathomorphology and immunohistochemistry, and CIC gene rupture detected by fluorescence in situ hybridization (FISH). Furthermore, the relevant literature was reviewed. Histologically, the tumor was composed of diffuse nests of small- to medium-sized juvenile round blue cells with hyperchromatic nuclei, prominent nucleoli and occasional mitotic signs. The tumor involved adipose tissue with no obvious hemorrhagic necrotic foci. Immunohistochemistry indicated scattered expression of CD99 in tumor cells. FISH examination suggested that the CIC gene was fragmented and translocated.

Nitric Oxide Attenuates Human Cytomegalovirus Infection yet Disrupts Neural Cell Differentiation and Tissue Organization.

Human cytomegalovirus (HCMV) is a prevalent betaherpesvirus that is asymptomatic in healthy individuals but can cause serious disease in immunocompromised patients. HCMV is also the leading cause of virus-mediated birth defects. Many of these defects manifest within the central nervous system and include microcephaly, sensorineural hearing loss, and cognitive developmental delays. Nitric oxide is a critical effector molecule produced as a component of the innate immune response during infection. Congenitally infected fetal brains show regions of brain damage, including necrotic foci with infiltrating macrophages and microglia, cell types that produce nitric oxide during infection. Using a 3-dimensional cortical organoid model, we demonstrate that nitric oxide inhibits HCMV spread and simultaneously disrupts neural rosette structures, resulting in tissue disorganization. Nitric oxide also attenuates HCMV replication in 2-dimensional cultures of neural progenitor cells (NPCs), a prominent cell type in cortical organoids that differentiate into neurons and glial cells. The multipotency factor SOX2 was decreased during nitric oxide exposure, suggesting that early neural differentiation is affected. Nitric oxide also reduced maximal mitochondrial respiration in both uninfected and infected NPCs. We determined that this reduction likely influences neural differentiation, as neurons (Tuj1+ GFAP- Nestin-) and glial populations (Tuj1- GFAP+ Nestin-) were reduced following differentiation. Our studies indicate a prominent, immunopathogenic role of nitric oxide in promoting developmental defects within the brain despite its antiviral activity during congenital HCMV infection. IMPORTANCE Human cytomegalovirus (HCMV) is the leading cause of virus-mediated congenital birth defects. Congenitally infected infants can have a variety of symptoms manifesting within the central nervous system. The use of 3-dimensional (3-D) cortical organoids to model infection of the fetal brain has advanced the current understanding of development and allowed broader investigation of the mechanisms behind disease. However, the impact of the innate immune molecule nitric oxide during HCMV infection has not been explored in neural cells or cortical 3-D models. Here, we investigated the effect of nitric oxide on cortical development during HCMV infection. We demonstrate that nitric oxide plays an antiviral role during infection yet results in disorganized cortical tissue. Nitric oxide contributes to differentiation defects of neuron and glial cells from neural progenitor cells despite inhibiting viral replication. Our results indicate that immunopathogenic consequences of nitric oxide during congenital infection promote developmental defects that undermine its antiviral activity.

Особливості розвитку панкреатиту на тлі деяких ревматичних захворювань

The purpose of the study was to evaluate the main pathogenetic mechanisms of pancreatic lesions on the background of systemic connective tissue diseases based on the analytical analysis of modern literature data. Materials and methods. Bibliosemantic and analytical methods were used in the research. Results and discussion. The main pathogenetic link of the pancreatitis development in patients with systemic connective tissue diseases is vasculitis of the pancreas. Increased expression of adhesion molecules with activation of leukocytes and endothelial cells, deposition of circulating immune complexes in the vascular wall, production of antibodies to endothelial cells, capillary basement membranes play an important role in this process. In systemic lupus erythematosus, according to various authors, the frequency of arteritis varies greatly: rates range from 6.2-7.4 to 53%. In rheumatoid arthritis, the frequency of arteritis of the pancreatic vessels reaches 50%, in systemic sclerosis – 17%. Secondary Sjogren's syndrome is associated with autoimmune pancreatitis in a quarter of cases, but is not the cause. In diseases such as rheumatoid arthritis, systemic scleroderma and systemic lupus erythematosus, antibodies that can attack phospholipids of cell membranes are produced. Antiphospholipid syndrome develops often in systemic lupus erythematosus (70% of cases). In rheumatic fever patients’ changes in the pancreas were studied only in single studies. The main mechanism of pathogenesis of both acute and chronic pancreatitis in nodular periarteritis is the involvement of small and medium arteries of the pancreas in the pathological process. In granulomatous polyangiitis in the pancreas reveals vascular-granulomatous changes, resulting in the formation of extravasations, necrotic foci, foci of atrophy, sclerosis. In IgA vasculitis, changes in the structure of the pancreas are minimal or there are isolated small subcapsular hemorrhages. It is established that metabolic disorders occur in many rheumatic diseases. Thus, reduced glucose tolerance is observed in 7–74% of patients, hypercholesterolemia and triglyceridemia – in 50–75%, hypertension – in 25–50% of cases. Conclusion. Thus, the diagnostic approach to the pancreatitis in systemic connective tissue diseases is very difficult. Its manifestations are masked by damage of the other organs. The availability of more sensitive diagnostic methods, their accessibility can provide an opportunity to detect symptoms of pancreatitis earlier, which will contribute to the appointment of optimal treatment, improvement of the prognosis, quality of life and survival of such patients

Abortion outbreak in a sheep flock caused by Toxoplasma gondii clonal type III.

Toxoplasma gondii is a major cause of reproductive losses in small ruminants in several countries. We describe here an outbreak of T. gondii-associated abortion in sheep in Southern Brazil. The flock was comprised of 55 adult sheep, and late-term abortions and stillbirths were detected in 15/36 (41.66%) gestating ewes. Serum samples collected from 45 sheep were tested for T. gondii through indirect immunofluorescence assay; IgM and IgG positive results were detected in 44.44% (20/45) and 86.67% (39/45) of the cases, respectively. Four fetuses and two placentas were pathologically evaluated. Gross changes were restricted to fetal membranes and were characterized by multifocal white areas in the cotyledons. Microscopically, these areas corresponded to necrotic foci affecting the chorionic epithelium accompanied by rare cysts of T. gondii. The main histological change in fetal tissues consisted of well-demarked and sparsely distributed necrotic foci in the central nervous system. Tissue samples from all four fetuses and one placenta had positive PCR results for T. gondii. Restriction fragment length polymorphism (RFLP) genotyping using ten markers (SAG1, 5'-3'SAG2, alt.SAG2, SGA3, BTUB, GRA6, c22-8, c29-2, L358, and PK1) was carried out on one sample, and results were consistent with T. gondii clonal type III (ToxoDB-PCR-RFLP genotype #2, TgCpBr4).

Features of the pathomorphosis of fire bullet wounds of the abdomen with damage of the colon

The article shows the features of the pathomorphosis of gunshot bullet wounds to the abdomen with damage to the colon. Various options for the course of repair and regeneration of the colon after surgical treatment and in the presence of postoperative complications in wounded patients with and without concomitant pathology of the colon are provided. It is shown that the etiology and pathogenesis of a penetrating gunshot wound of the intestine has mechanical and metabolic aspects. It has been proven that the greatest impact force on the intestine falls on the outside, on the peritoneum, which is often worn away from the longitudinal layer of the muscle wall of the intestine. It is given that the restructuring of the structure and function of the colon in chronic colitis after a gunshot wound leads to an exacerbation of the chronic process in all membranes. It is shown that damage to the intestinal mucosa occurs simultaneously with the destruction of intestinal tissues, but depends on general and local immunity. Infiltration of the site of the lesion by neutrophil granulocytes leads to the disposal of the entire wound or the development of complications. The structural and functional state of intestinal lymphatic follicles makes it possible to maintain intestinal immune protection, bacterial microflora and digestion. The method of choice for surgical repair of the consequences penetrating into the abdominal cavity of a gunshot wound will be the maximum resection of necrotic foci, large hemorrhages to avoid adhesion disease. At different levels, depending on the wound process, the structural and functional reconstruction is completely different, which is due to the individual feature of the structure and function, which affects the surgeon's desire for a justified radical or, on the contrary, for an organ-preserving operation. Keywords: histological examination, gunshot wound, colon injury.

P-195 Do the presence of necrotic foci and/or separate blastomeres, the blastocoele expansion degree affect pregnancy outcomes of frozen-thawed euploid blastocysts transfer cycles?

Abstract Study question Do the presence of necrotic foci and/or the presence of separate blastomeres and the blastocoele expansion degree affect pregnancy outcomes of frozen-thawed euploid embryo transfer cycles? Summary answer Significant correlations were observed between pregnancy outcomes and the degree of blastocoele expansion, the presence of necrotic foci or separate blastomeres in the euploid embryo. What is known already Implantation failure and pregnancy losses may occur despite the selection of a healthy euploid embryo for transfer and the elimination of other risk factors. Blastocyst morphology is known to affect pregnancy outcomes, but the effect of necrotic foci and/or separate blastomeres in the embryo on pregnancy outcomes needs further investigation. Study design, size, duration This is a retrospective cohort study and was conducted at ART and Reproductive Genetics Centre, Memorial, Sisli Hospital, Istanbul, Turkey between January 2017 and September 2021. A total of 2758 frozen-thawed euploid embryo transfer cycles were included in the study. Participants/materials, setting, methods After thawing, the embryos were divided into groups according to their morphological grades, whether there were necrotic foci and whether there were separate blastomeres, and were evaluated in terms of pregnancy outcomes. Blastocysts were graded by using Gardner and Schoolcraft’s grading system. Ongoing pregnancy was defined as a pregnancy that had reached 20 weeks. Miscarriage was defined as a pregnancy loss occurring before the 20th gestational week. Main results and the role of chance Our data showed that the presence of necrotic foci in the inner cell mass or trophectoderm reduced the ongoing pregnancy rates and increased the miscarriage rates. The ongoing pregnancy rate was lower (41.0%, vs 60.0%, p < 0.001) and the miscarriage rate was higher (27.3% vs 19.8%, p < 0.05) in the group with necrotic foci than in the group without necrotic foci. The presence of separate blastomeres decreased the ongoing pregnancy rates (50.3% in the group with separate blastomeres, 61.8% in the group without separate blastomeres) (p < 0.001) and increased the miscarriage rates (25.3% in the group with separate blastomeres, 18.8% in the group without separate blastomeres) (p > 0.004). The ongoing pregnancy rates for blastocoele expansion degrees of 2, 3, 4, 5, and 6 were 39.5%, 38.3%, 59.3%, 59.8%, and 61.4%, respectively and the miscarriage rates for blastocoele expansion degrees of 2, 3, 4, 5, and 6 were 35%, 33.3%, 21%, 21.2%, 18.4%, respectively. Embryos with degrees of expansion grade ≤ 3 had lower ongoing pregnancy rates and higher miscarriage rates than those with degrees of expansion > 3 (p < 0.01). Limitations, reasons for caution Retrospective study. Wider implications of the findings When choosing the embryo to be transferred in cases with more than one euploid embryo, the selection should be made by considering the blastocoele expansion degrees and the presence of necrotic foci and separate blastomeres in the embryo. Trial registration number not applicable

IMG-01. Quantitative Direct Sodium (23Na) MRI in Pediatric Gliomas

BACKGROUND: The treatment of pediatric gliomas is typically assessed with proton (1H) MRI, which can have limitations. 23Na MRI has been shown in adult brain tumors to measure intra-tumoral total sodium concentration as a correlate of tumor proliferation. 23Na MRI sodium studies in pediatric patients are lacking. PURPOSE: (1) To compare total sodium concentration (TSC) between pediatric glioma and non-neoplastic brain tissue using 23Na MRI; (2) Compare tissue conspicuity of bound sodium concentration (BSC) using 23Na MRI dual echo relative to TSC imaging. MATERIALS AND METHODS: TSC was measured in: (1) non-neoplastic brain tissues and (2) three types of manually segmented gliomas [diffuse intrinsic brainstem glioma (DIPG), recurrent supratentorial low-grade glioma (LGG), and high-grade glioma (HGG)] on sodium MRI images co-registered with proton MRI. In a subset of patients, serial changes in both TSC and BSC (dual echo 23Na MRI) were assessed for tissue conspicuity using voxel-based parametric maps. RESULTS: Twenty-six pediatric patients with gliomas (median age of 12.0 years, range 4.9 – 23.3 years) were scanned with 23Na MRI. Uninvolved tissues demonstrated a range of TSC values similar to published adult values. DIPG treated with RT demonstrated higher TSC values than the uninvolved infratentorial tissues (P<0.001). Recurrent supratentorial LGG and HGG exhibited higher TSC values than the uninvolved white matter (WM) and gray matter (GM) (P<0.002 for LGG, and P<0.02 for HGG). The dual echo 23Na MRI suppresses the sodium signal within both CSF and necrotic foci, resulting in improved conspicuity of both non-neoplastic and neoplastic, compared to serial TSC imaging. CONCLUSION: Quantitative 23Na MRI of pediatric gliomas demonstrates a range of values that are higher than non-neoplastic tissues. Dual echo 23Na MRI of BCS improves tissue conspicuity relative to TSC imaging. Future studies are needed to determine the value of 23Na MRI in delineating therapeutic responses in pediatric gliomas.

Duodenal Necrosis and Nonvariceal Digestive Bleeding After Terlipressin Administration for Treatment of Hepatorenal Syndrome: a Case Report of a Novel Side Effect of a Commonly Used Drug

BackgroundTerlipressin is widely used for treatment of hepatorenal syndrome and variceal bleeding in cirrhotic patients. However, it may be associated with side effects, especially those related to vasoconstriction, such as myocardial infarction or intestinal ischemia. This is a case report of a cirrhotic patient with nonvariceal upper gastrointestinal bleeding after duodenal necrosis due to the use of terlipressin, a novel side effect not yet described in literature to the best of our knowledge. Case reportA 51-year-old male patient, with alcoholic liver cirrhosis and hepatitis C virus infection, was admitted presenting oliguria associated with severe ascites and lower limb edema. His Model for End Stage Liver Disease–Sodium score was 19 and his serum creatine level was 2.12 mg/dL. Albumin infusion was performed for 48 hours, but his serum creatinine level reached 3.46 mg/dL. Terlipressin infusion was started in continuous infusion and serum creatinine levels progressively decreased. However, the patient presented hemorrhagic shock secondary to hematemesis after 7 days. Upper digestive endoscopy showed an extensive ulcerated lesion in the duodenal bulb, reaching 70% of its lumen, with hematic residues and necrotic foci. Terlipressin was suspended and proton pump inhibitors were started. Despite intensive care, the patient developed severe encephalopathy and reentrant seizures. He eventually died 10 days after the bleeding event. ConclusionsWe described a case of nonvariceal upper gastrointestinal bleeding secondary to duodenal necrosis, which was caused by visceral ischemia induced by terlipressin. Given its fatality potential, this novel side effect should be remembered when using this medication in cirrhotic patients.

A Malignant Mimicker: Features of Kikuchi-Fujimoto Disease in the Pediatric Population.

Kikuchi-Fujimoto disease (KFD) is a rare, benign, and self-limited disease that presents with cervical lymphadenopathy and systemic symptoms. Histologic evaluation is often necessary to differentiate KFD from other entities. Electronic medical records and diagnostic material were reviewed for 14 children diagnosed with KFD and 6 children diagnosed with infectious mononucleosis (IM) from 2013-2021. Four cases of KFD were further characterized using targeted DNA-based next-generation sequencing. Systemic symptoms were present in 86% (n = 12/14) of KFD patients, the most common being fever. Laboratory values worrisome for malignancy included cytopenia(s) (n = 9/12), elevated ESR and/or CRP (n = 9/12), elevated ferritin (n = 7/7), and elevated LDH (n = 7/10). Histologically, lymph nodes showed characteristic necrotic foci without neutrophils surrounded by MPO+ "crescentic" histiocytes. Immunoblasts and CD123+ plasmacytoid dendritic cells (pDCs) were also increased surrounding the necrosis. IM lymph nodes showed similar features when necrosis was present but increases in pDCs were patchy and rare neutrophils were seen in the necrotic foci. Molecular analysis of 4 KFD cases did not identify pathogenic variants. While the signs/symptoms of KFD are worrisome, there are pathologic features that help differentiate it from potential mimics. We did not identify characteristic molecular features to aid in the work-up of these cases.

Quantitative Sodium (23Na) MRI in Pediatric Gliomas: Initial Experience.

Background: 23Na MRI correlates with tumor proliferation, and studies in pediatric patients are lacking. The purpose of the study: (1) to compare total sodium concentration (TSC) between pediatric glioma and non-neoplastic brain tissue using 23Na MRI; (2) compare tissue conspicuity of bound sodium concentration (BSC) using 23Na MRI dual echo relative to TSC imaging. Methods: TSC was measured in: (1) non-neoplastic brain tissues and (2) three types of manually segmented gliomas (diffuse intrinsic brainstem glioma (DIPG), recurrent supratentorial low-grade glioma (LGG), and high-grade glioma (HGG)). In a subset of patients, serial changes in both TSC and BSC (dual echo 23Na MRI) were assessed. Results: Twenty-six pediatric patients with gliomas (median age of 12.0 years, range 4.9–23.3 years) were scanned with 23Na MRI. DIPG treated with RT demonstrated higher TSC values than the uninvolved infratentorial tissues (p < 0.001). Recurrent supratentorial LGG and HGG exhibited higher TSC values than the uninvolved white matter (WM) and gray matter (GM) (p < 0.002 for LGG, and p < 0.02 for HGG). The dual echo 23Na MRI suppressed the sodium signal within both CSF and necrotic foci. Conclusion: Quantitative 23Na MRI of pediatric gliomas demonstrates a range of values that are higher than non-neoplastic tissues. Dual echo 23Na MRI of BCS improves tissue conspicuity relative to TSC imaging.

Hepatocyte β‐catenin is regulated by endothelial cell‐derived Wnt2 and Wnt9b to govern liver metabolic zonation and regeneration

BackgroundWnt/β‐catenin signaling pathway regulates hepatic metabolic zonation (MZ) and liver regeneration (LR) after surgical or toxicant injury. Central vein endothelial cells (CVECs) are the main source of Wnts regulating MZ, while liver sinusoidal ECs (LSECs) are the major source of Wnts regulating LR after 70% partial hepatectomy (PH). Of the 19 Wnt genes, Wnt2 and Wnt9b were reported to be expressed in CVECs and the same 2 Wnts were also upregulated in LSECs isolated from regenerating livers at 12h post PH. However, conclusive evidence of the specific roles of Wnt2 and Wnt9b in regulating MZ and LR, is lacking.MethodsHere, we report generation of Wnt2‐floxed mice and generation of Wnt2‐Wnt9b‐double‐floxed mice, which were then bred to lymphatic vessel endothelial hyaluronan receptor 1 (Lyve1)‐Cre mice to delete Wnt2, Wnt9b or both from both CVECs and LSECs referred to as EC knockouts (KO). We characterize EC‐Wnt2‐KO, EC‐Wnt9b‐KO, and EC‐Wnt2‐9b‐double KO (DKO), and assess for baseline phenotype, MZ, and LR after PH.ResultsUsing reporter mice, we first reaffirmed that Lyve1‐Cre induces recombination of floxed alleles in both CVECs and LSECs. Liver weight to body weight ratio (LW/BW) was lower in EC‐Wnt2‐9b‐DKO mice. Subsets of these mice showed an abnormal increase in one liver lobe size and mass at the expense of other lobes, along with mild periportal fibrosis. Male but not female EC‐Wnt2‐KO and EC‐Wnt9b‐KO mice had partial loss of pericentral expression of glutamine synthetase (GS), cytochrome P450 2e1 (Cyp2e1), and cytochrome P450 1a2 (Cyp1a2). Both male and female EC‐Wnt2‐9b‐DKOs lacked GS, Cyp2e1 and Cyp1a2, phenocopying EC‐Wntless‐KO mice in which all Wnts secretion from ECs were inhibited. After PH, EC‐Wnt2‐KO and EC‐Wnt9b‐KO mice showed decreased expression of Cyclin D1, Ki67 and incorporation of BrdU at 40h, which was even lower in EC‐Wnt2‐9b‐DKOs. The subset of EC‐Wnt2‐9b‐DKO mice with abnormal lobar morphology developed multiple necrotic foci infiltrated with immune cells, had a detrimental delay of LR and exhibited increased mortality after PH.ConclusionWnt2 and Wnt9b from CVECs play additive roles in controlling β‐catenin pericentral target gene expression. Additionally, Wnt2 and Wnt9b from LSECs play additive roles in regulating β‐catenin activation during LR after PH. Further studies are needed to address how and why ECs are the chief source of these two Wnts to regulate MZ and LR.

Autopsy Histopathologic Cardiac Findings in 2 Adolescents Following the Second COVID-19 Vaccine Dose

Autopsy Histopathologic Cardiac Findings in 2 Adolescents Following the Second COVID-19 Vaccine Dose

An Examination of the Effect of Rutin against Neurotoxicity Induced by Ciprofloxacin Antibiotic in Wistar Rats.

Rutin is a citrus flavonoid that exists in different types of food, such as fruits, tea, as well as vegetables, and is considered a natural antioxidant. This study aimed to investigate the therapeutic role of Rutin in oxidative stress-induced in Wistar rats exposed to Ciprofloxacin (CPX). The study included 36 healthy adult Wistar rats, which were randomly divided into six groups (n=6). The control group (C) received normal drinking water for 20 days. The first treatment group (T1) received Rutin at a dose of 50 mg/kg of b.w for 20 days. The second treatment group (T2) received CPX antibiotic at a dose of 14 mg/kg of b.w for 20 days. The third treatment group (T3) received Rutin at a dose of 50 mg/kg of b.w for 20 days, and afterward, they received CPX antibiotic at a dose of 14 mg/kg of b.w for 20 days. The fourth treatment group (T4) received CPX antibiotic at a dose of 14 mg/kg of b.w for 20 days, and then, they received Rutin at a dose of 50 mg/kg of b.w for 20 days. The fifth treatment group (T5) received CPX antibiotic at a dose of 14 mg/ kg of b.w and Rutin at a dose of 50 mg/ kg of b.w together for 20 days. All the treatments were administrated by oral gavage. Analysis of the recorded data showed a significant increase (P<0.05) in the concentration of Methylenedioxyamphetamine (MDA) in the T2 group, compared to the other groups. The MDA level significantly (P<0.05) increased in the T3 group (2.29±0.04), compared to the C (1.71±0.01), T1 (1.54±0.04), T4 (1.18±0.02), and T5 (1.29±0.03) groups. However, there were no significant differences (P<0.05) between the C (1.71±0.01) and T1 (1.54±0.04) groups, as well as the T4 (1.18±0.02) and T5 (1.29±0.03) groups with regards to the MDA. The results clarified a significant increase (P<0.05) in the antioxidant activity, Glutathione (GSH), Superoxide dismutase (SOD), and Catalase (CAT) contents in the T1 group, determined at 5.91±0.26, 5.78±0.02, and 1.98±0.05, respectively, compared to the other groups. The lowest antioxidant activity, GSH, SOD, and CAT contents were recorded in the T2 group, in comparison with the other groups (P<0.05). The findings revealed that the level of SOD, GSH, and CAT in the T4 and T5 groups significantly (P<0.05) increased, compared to the T2 and T3 groups. Histological examination of the slides obtained from the brain demonstrated that in the T2 group, some histopathological changes were observed, compared to the C, T1, T4, and T5 groups. These changes were as follows: 1) damaged and clear blood vessel congestion with the deposition of fibrous networks, 2) brain edema, 3) multiple necrotic foci, 4) accumulation of neutrophils, and 5) simple histopathological changes in the brain of animals in the T2 group, compared to the other groups. It is, therefore, concluded that Rutin supplementation at a dose of 50 mg/kg b.w can be the most appropriate dose in protecting brain tissue against tissue damages caused by CPX.

Mice Dually Disrupted for Nod2 and Mincle Manifest Early Bacteriological Control but Late Susceptibility During Mycobacterium tuberculosis Infection.

Pattern recognition receptors Mincle and NOD2 have been implicated in mycobacterial immunity. However, knockout (KO) animal infection studies with Mycobacterium tuberculosis (Mtb) have had mild/delayed phenotypes. Given that genetic susceptibility to infectious diseases can be polygenic, we hypothesized that murine double knockout (DKO) of Mincle and Nod2 would result in exacerbation of altered immunity to mycobacterial infection leading to a more extreme phenotype than either KO alone. To test this hypothesis, we monitored bacterial burden, immune responses and survival following in vivo infections with Mtb in DKO mice for comparison to wildtype (WT) and single KOs. Bacterial burden and immune responses were not significantly affected at 3 and 6 weeks after infection in all mutant mice. At later timepoints, Nod2-KO mice had reduced survival compared to wildtype mice, and Mincle-KO survival was intermediate. Unexpectedly, dual disruption had no further effect; rather, DKO mice phenocopied Nod2-KO mice. We observed that Mtb-related death, exclusively in mice with disrupted Nod2, was accompanied by greater pulmonary cell death and distinct large necrotic foci. Therefore, determining how these receptors contribute to mycobacterial resistance will require analysis of immunophenotypes and their consequences on host pathology.

Fatal toxoplasmosis in Little Penguins (Eudyptula minor) from Penguin Island, Western Australia.

Routine post mortems of deceased penguins from Penguin Island, Western Australia, found that a temporal cluster of cases presented with characteristic gross and microscopic changes, namely birds in good body condition with hepatomegaly and splenomegaly, multifocal hepatic and splenic necrosis and numerous, 1–2 μm diameter protozoan parasites within the necrotic foci.Electron microscopy identified the protozoa as belonging to the phylum Apicomplexa. Molecular investigations by PCR gave inconsistent results. PCR performed by an external laboratory identified a novel Haemoproteus spp. organism in samples from 4 of 10 cases from this group, while PCR at Murdoch University identified Toxoplasma gondii in 12 of 13 cases (including 9 of the 10 assayed at the external laboratory). Immunohistochemistry of formalin fixed tissues also identified Toxoplasma in the hepatic and splenic lesions.The distinctive mortalities which were observed in this group of penguins are attributed to a fulminant toxoplasmosis, with a concurrent Haemoproteus infection in some cases. Though the clinical signs of infection are unknown, the gross and microscopic appearance at post mortem is sufficiently characteristic to allow a diagnosis to be made on these features. Definitive confirmation of Toxoplasma infection can be made by immunohistochemistry or PCR.

Histopathologic and MR Imaging Appearance of Spontaneous and Radiation-Induced Necrosis in Uveal Melanomas: Initial Results.

Simple SummaryUveal melanomas may undergo necrosis, both spontaneously or following radiotherapy. Nowadays radiotherapy is the preferred treatment, whereas enucleation of the eye is used in selected cases. In order to differentiate the effects of radiotherapy from spontaneous degenerative changes in uveal melanomas, we compared the appearance of necrosis, both from a histopathological point of view and from the perspective of MR imaging, in two groups of patients with uveal melanoma: a group who had undergone previous proton beam radiotherapy (secondary enucleation); a control group who had undergone enucleation without any previous radiotherapy treatment (primary enucleation). Irradiated and nonirradiated uveal melanomas differ on the basis of the histological appearance, the MR imaging appearance and the distribution of necrosis. We hope that the findings we observed could be extended to all patients with uveal melanomas treated with radiotherapy, and may enhance the accuracy of radiologists in evaluating MR examinations after radiotherapy.Necrosis in uveal melanomas can be spontaneous or induced by radiotherapy. The purpose of our study was to compare the histopathologic and MRI findings of radiation-induced necrosis of a group of proton beam-irradiated uveal melanomas with those of spontaneous necrosis of a control group of patients undergoing primary enucleation. 11 uveal melanomas who had undergone proton beam radiotherapy, MRI and secondary enucleation, and a control group of 15 untreated uveal melanomas who had undergone MRI and primary enucleation were retrospectively identified. Within the irradiated and nonirradiated group, 7 and 6 eyes with histological evidence of necrosis respectively, were furtherly selected for the final analysis; the appearance of necrosis was assessed at histopathologic examination and MRI. Irradiated melanomas showed a higher degree of necrosis as compared with nonirradiated tumors. Irradiated and nonirradiated lesions differed based on the appearance and distribution of necrosis. Irradiated tumors showed large necrotic foci, sharply demarcated from the viable neoplastic tissue; nonirradiated tumors demonstrated small, distinct foci of necrosis. Radiation-induced necrosis, more pigmented than surrounding viable tumor, displayed high signal intensity on T1-weighted and low signal intensity on T2-weighted images. The hemorrhagic/coagulative necrosis, more prevalent in nonirradiated tumors (4 out of 6 vs. 1 out of 7 cases), appeared hyperintense on T2-weighted and hypointense on T1-weighted images. Our study boosts the capability to recognize radiation-induced alterations in uveal melanomas at MRI and may improve the accuracy of radiologists in the evaluation of follow-up MR examination after radiotherapy.

RESULTS OF A MORPHOLOGICAL STUDY OF MUCORMYCOSIS COMPLICATIONS OF THE MAXILLOFACIAL AREA AFTER COVID-19

This article presents the results of a morphological examination of facial mucosa complications after COVID-19. Infection of patients with COVID-19 with mucormycosis in the oral cavity is manifested in the form of discoloration of the mucous membrane in the area of the palate, swelling, ulcers, necrotic foci on the palate, hard palate and jaw bones, and the dark surface of the bone surface (Brandao et al ., 2020). It should be borne in mind that the recent emergence and development of mucormycosis with COVID-19 is not considered to be fully interrelated, but sufficient causes and conditions for the occurrence of this process during the pandemic, as well as the presence of somatic comorbidities, chronic microbial foci in patients.