Focal Necrosis Research Articles

Prevalence and pathological investigation of fowl typhoid in commercial poultry farms at the Rajshahi City Corporation area of Bangladesh

The present study was conducted to determine the prevalence of Fowl typhoid in apparently healthy, sick and dead birds at Rajshahi city corporation area of Bangladesh. A total of 500 birds (50 from each farm) and 30 different organs (liver from 10, ovary from 8, heart from 7, and caecal tonsils from 5) were randomly collected from different commercial poultry farms during the period from January 2018 to December 2018. The prevalence study was performed based on history, clinical signs, symptoms exhibited by the individual bird of a flock during the observation of farms, and illness of birds. The suspected birds were subjected to necropsy examination. During sample collection, clinical signs and gross necropsy changes were recorded very carefully. The collected tissues were fixed, processed, sectioned, stained, and studied light microscopically. The routine histopathological method was used for the detection of tissue-level alterations in Fowl typhoid infected cases. The prevalence of Fowl typhoid in apparently healthy birds of different poultry farms was 8.2%, and 23.33% of organs were involved. Grossly, the liver was enlarged, congested and revealed bronze discoloration with focal necrosis in the surface of the liver. Old raised hemorrhages were found in the caecal tonsils. Congested, deformed, and pedunculated ova were other important findings. Microscopically, the sections of the liver showing multifocal necrosis with infiltration of heterophils and reticulo-endothelial cells.
 Res. Agric., Livest. Fish.8(2): 201-209, August 2021

First report of bacillary hemoglobinuria in buffaloes / Primeiro relato de hemoglobinúria bacilar em búfalos

We herein describe a typical episode of bacillary hemoglobinuria in buffalloes, triggered by liver fluke invasion proved by pathognomonic macro and micro lesions of fasciolosis in the biliary ducts and the nephrosis and hepatic focal necrosis characterizing the toxic-infectious process caused by Clostridium haemolyticum. This report is quite similar to another one described by AHOURAI et al. (1990) in cattle following liver fluke invasion and C. haemolyticum isolation and we both agree with the fact that foci of ischemic of toxic necrosis serve as a focus in which clostridial spores might vegetate and cause the disease by producing toxins. Vaccination with bacterin or toxoids is the most effective measure for preventing these histotoxic clostridial diseases since the endospores of the microorganism persist in the environment. Also, as the process is triggered by fluke liver migration, the prevention should cover the control of this trematode as well. Although the pathogenicity of bacillary hemoglobinuria is well known, there are only a few reports currently available, and to our knowledge this is the first case of the disease described in buffaloes.

Histopathological and ultrastructural study of carotid atherosclerotic plaques: a study of four cases

ABSTRACT To clarify the characteristics and origin of the cellular components in atherosclerosis, carotid atherosclerotic plaques (CAPs) of four patients were studied by light microscopy using hematoxylin-eosin, Congo red and alpha-smooth-muscle actin stains, and by transmission electron microscopy of different regions of CAPs. By light microscopy, CAPs were composed of 1) a fibrous cap; 2) an atherosclerotic core presenting focal fibrosis, neovascularization, hemorrhage, necrosis, chondrification and ossification; and 3) a basal band composed of a hyperplasic pseudo-media and affected tunica media. Ultrastructurally, the CAPs contained a diversity of cells including fibroblasts, myofibroblasts, osteochondrocytes, vascular smooth-muscle cells, foam cells and other myoid cells characterized by varied features of the above mentioned cells. The results indicated that CAPs were derived from a proliferation of multipotential mesenchymal stem cells, leading to the presence of degenerated foam cells and lipid-laden cells.

Experimental modeling of chemical burning of the esophagus using different concentrations of alkali solution

The purpose and objectives of the study: is to create an experimental model of a chemical burn of the esophagus with alkali to study the pathological transformation of the tissues of the upper gastrointestinal tract.Materials and methods. On the basis of the Department of Experimental Medicine with a vivarium of the Privolzhsky Research Medical University, the study of a chemical burn of the esophagus was carried out on 15 sexually mature male Wistar rats. The burn was simulated by exposure to caustic soda (NaOH) with a concentration of 20 %, 15 %, 10 % and 5 % in a volume of 1 ml. As part of the morphological study, the experimental material was fixed in 10 % formalin. After fixation, the preparations were sent to a standard histological wiring using an Excelsior ES apparatus (Thermo Scientific). Pouring into paraffin blocks using the “HistoStar” filling station (Thermo Scientific), staining with hematoxylin and eosin. For morphometric processing and creation of a video archive of the obtained material, a Leica 2500 microscope, ×4, ×10, ×20, ×40, objective, ×10 eyepiece based on the morphology department of NIITO PIMU was used.Results. Seeding with a 20 % alkali solution for animals turned out to be incompatible with life, since a day after the injection of the substance, 3 rats died, 2 were in an agonal state. Morphological examination revealed total necrosis (100 %) of the epithelial lining up to the muscle layer and partially in the muscle layer. When burned with a 15 % NaOH solution, the males were in a very serious condition, out of 5 inoculated in 2 cases, a lethal outcome was noted on the 1st day. Histological examination revealed massive necrosis (70 %) of the epithelial lining. The effect of 10 % alkali on the general condition of the animals did not show a pronounced severity of injury. Necrosis was diagnosed on 15 % of the area of the epithelial lining. A burn with 5 % sodium hydroxide solution did not provoke a severity incompatible with life. In this condition, focal necrosis was revealed, occupying about 5 % of the organ area.Conclusion. Seeds with 10 % and 5 % caustic solutions are relevant for further experimental research, since they make it possible to test different methods of diagnostics, treatment and prevention of scarring at different depths and morphological features of damage.

Poorly differentiated chordoma showing loss of SMARCB1/INI1: Clinicopathological and radiological spectrum of nine cases, including uncommon features of a relatively under-recognized entity

Poorly differentiated chordoma is a newly recognized entity in the recent World Health Organization (WHO) classification of tumors of soft tissue and bone. Slightly over 60 such cases have been documented.Herein, we present a clinicopathological profile, including radiological features, of nine cases, which occurred in five males and four females, with age varying from 1 to 29 years (median = 43), in the cervical spine (n = 2), skull base (n = 2), clivus (n = 2), thoracic spine (n = 1) lumbar spine (n = 1) and coccyx (n = 1) Average tumor size was 4.8 cm. None of the 6-referral cases was diagnosed as a poorly differentiated chordoma at the referring laboratory.Histopathologically, all cases displayed a cellular tumor comprising polygonal cells (n = 9) displaying moderate to marked nuclear pleomorphism with prominent nucleoli (n = 7), eosinophilic (n = 9) to vacuolated cytoplasm (n = 7), rhabdoid morphology (n = 4), interspersed mitotic figures (n = 5), focal necrosis (n = 6) and inflammatory cells (n = 9). A single tumor displayed areas resembling classic chordoma, transitioning into poorly differentiated areas. There were multinucleate giant cells and physaliphorous cells in two tumors, each, respectively. Immunohistochemically, tumor cells were positive for AE1/AE3 (7/7), EMA (7/7), cytokeratin (CK) MNF116 (1/1), OSCAR (1/1), brachyury (9/9, diffusely), S100P (4/7, mostly focally), and glypican 3(2/4). SMARCB1/INI1 was completely lost in all nine tumors. A single case tested by FISH showed homozygous deletion of the SMARCB1 gene.Therapeutically (n = 7), all patients were treated with surgical resection (invariably incomplete) (n = 5), followed by adjuvant radiation therapy (n = 4) and chemotherapy (n = 4). While a single patient partially responded to treatment and another patient is alive with no evidence of disease after 23 years, three patients died of disease, six, eight, and 11 months post-diagnosis, despite adjuvant treatments. A single patient presented with a metastatic lung nodule, while another developed widespread metastasis.Poorly differentiated chordomas display a spectrum of features, are associated with a lower index of suspicion for a diagnosis, and display aggressive outcomes. Critical analysis of radiological and histopathological features, including necessary immunostains (brachyury and SMARCB1/INI1), is necessary for their timely diagnosis. These tumors show loss of SMARCB1/INI1 immunostaining and homozygous deletion of INI1/SMARCB1 gene.

Acute and Delayed Doxorubicin-Induced Myocardiotoxicity Associated with Elevation of Cardiac Biomarkers, Depletion of Cellular Antioxidant Enzymes, and Several Histopathological and Ultrastructural Changes.

Doxorubicin (DOX; Adricin) is an anthracycline antibiotic, which is an efficient anticancer chemotherapeutic agent that targets many types of adult and pediatric tumors, such as breast cancer, leukemia, and lymphomas. However, use of DOX is limited due to its cardiotoxic effects. This study sequentially investigated the mechanistic pathways of the cardiotoxic process of DOX in rats at different post-treatment periods using cumulative dose, which is used in therapeutic regimes. In this regard, 56 male albino rats were used for the experiment. The experimental animals were divided into seven groups (n = 8/group) based on dose and sacrifice schedule as follows: G1 (2 mg/kg body weight [BW] and sacrificed at day 4), G2 (4 mg/kg BW and sacrificed at day 8), G3 (6 mg/kg BW and sacrificed at day 15), G4 (8 mg/kg BW and sacrificed at day 30), G5 (10 mg/kg BW and sacrificed at day 60), G6 (10 mg/kg BW and sacrificed at day 90), and G7 (10 mg/kg BW and sacrificed at day 120). As expected, G1, G2, and G3-treated groups revealed features of acute toxic myocarditis associated with degenerative and necrotic changes in myocytes, mitochondrial damage, elevation of cardiac biomarkers, and depletion of cellular antioxidant enzymes. However, these changes increased in severity with subsequent treatment with the same dose until reaching a cumulative dose of 10 mg/kg BW for 30 d. Furthermore, after a cumulative dose of 10 mg/kg BW with a withdrawal period of 2–3 months, various predominant changes in chronicity were reported, such as disorganization and atrophy of myocytes, condensation and atrophy of mitochondria, degranulation of mast cells, and fibrosis with occasional focal necrosis, indicating incomplete elimination of DOX and/or its metabolites. Altogether, these data provide interesting observations associated with the cardiotoxic process of DOX in rats that would help understand the accompanying changes underlying the major toxic effects of the drug. Future research is suggested to explore more about the dose-dependent mechanisms of such induced toxicity of DOX that would help determine the proper doses and understand the resulting cardiomyopathy.

Seroprevalence and pathological studies of Salmonella infection in commercial white layer birds

The present study was conducted to determine the seroprevalence and pathology of Salmonella infection in white commercial layer birds of District Faisalabad during June 2018 and June 2020. The current study aimed to determine the isolation, identification of Salmonella gallinarum (S. gallinarum), its cultural prevalence, antimicrobial resistance, molecular characterization, and pathological lesions produced in different organs of commercial layer birds. Initial screening of poultry flocks was done through serum plate agglutination test followed by culturing in different media, motility test, molecular confirmation, and histopathology. Based on the serum plate agglutination test, seroprevalence in the commercial white layer in dead and live flocks was 40.09%. The cultural prevalence of Salmonella in the seropositive group was 75.36% and in the seronegative was 31.84%. Cultural prevalence in the liver of dead birds was 62.06%, in spleen 58.62%, and in cloacal swabs was 67.24%. A total of 178 isolates were characterized through cultural characteristic and motility tests, among them 63.48% isolates were S. gallinarum, and 36.51% isolates were S. pullorum. The antibiogram study revealed that all the tested isolates were resistant to amoxicillin, gentamycin, kanamycin, doxycyclin, and tetracyclin. While tested isolates were sensitive to ciprofloxacin against S. gallinarum. Pathologically liver was friable, showing bonze discoloration with focal necrosis, enteritis of various grades, mottled white spleen, and enlarged kidneys were found. Microscopically, leukocytic infiltration with focal necrosis and degeneration, in mucosa and submucosa of intestinal inflammatory cells were observed. In conclusion, the seroprevalence, antibiogram, and molecular characterization of Salmonella help to control the disease in a better way through bacterin production of local isolates.

Vitamin D modulates hepatic microRNAs and mitigates tamoxifen-induced steatohepatitis in female rats.

Tamoxifen (TAM) is a life-saving and cost-effective drug widely used in the prevention and treatment of breast cancer. However, the adverse effects of tamoxifen can lead to non-adherence and poor patient outcomes. Therefore, exploring novel strategies to improve TAM safety profile is crucial. Given the key role that vitamin D (VD) plays in modulating lipid metabolism and inflammation, in addition to its benefits in reducing risk and progression of breast cancer, we evaluated the protective potential of VD against TAM-induced hepatotoxicity focusing on lipid metabolism and microRNAs (miRNAs) regulation. Female rats were pretreated with VD as cholecalciferol (500 IU/kg/day, po) for 4weeks before receiving TAM (40 mg/kg/day, po) concurrently with VD during the fifth and sixth weeks. Liver histology, lipid profile and expression of genes, proteins, and miRNAs involved in lipid metabolism and inflammation were examined. TAM-induced steatohepatitis was evidenced by elevated liver triglycerides and cholesterol contents, increased serum miRNA-122 level, and ALT activity, in parallel with accumulation of lipid droplets, focal necrosis, and inflammatory cells infiltration in hepatocytes. Prophylactic use of VD mitigated TAM-induced steatohepatitis by modulating key transcription factors in the liver: PPAR-α, Srebf1, and NF-κB and their downstream genes/proteins Fas, CPT-1A, and TNF-α resulting in reduced hepatic lipids and suppressed pro-inflammatory signaling. Notably, VD pretreatment mitigated TAM-induced alterations in the expression of serum miRNA-122, hepatic miRNA-21, and miRNA-33. The combination therapy of VD and TAM has complementary benefits in terms of safety and not only efficacy and should be further investigated clinically.

Long Term Effects of Streptozotocin Induced Diabetes Mellitus on Hepatic, Nephrotic and Cardiac Physiology of Female Wistar Rats

Background: Diabetes mellitus is a metabolic disorder which leads to complications that affect the heart, kidney, liver and other vital organs. Most reports on diabetes have focused on diabetes induction using male rat models in short term studies.Objective: Here, we described the induction of diabetes in female rat and the complications of diabetes following long term hyperglycemia in female Wistar rats.Method: Rats were assigned into two groups: control (n=10) and diabetic (n=10). The latter was administered a single (50mg/Kg body weight) intraperitoneal injection of streptozotocin. Bodyweight and blood glucose were assessed for 14 weeks, after which the animals were sacrificed and biochemical and morphology parameters of the liver, kidney and heart were determined.Results: Diabetic rats showed continuous emaciation post STZ induction. The glycated haemoglobin, protein level, lipid profile, liver and kidney function markers were significantly different (p<0.05) from the control. Catalase, superoxide dismutase and glutathione-s-transferase activities were also significantly reduced in the heart, liver and kidney, and a concomitant increase in malondialdehyde concentration was observed. Focal tubular necrosis, pulmonary congestion and mild hyperplasia of kupffer cells were observed in the tissues and all tissues showed negative CD79a expression.Conclusion: This study provides data that could be useful for modelling long-term diabetes mellitus studies in female experimental rat models.

Cholesterol-functionalized DNA/RNA heteroduplexes cross the blood-brain barrier and knock down genes in the rodent CNS.

Achieving regulation of endogenous gene expression in the central nervous system (CNS) with antisense oligonucleotides (ASOs) administered systemically would facilitate the development of ASO-based therapies for neurological diseases. We demonstrate that DNA/RNA heteroduplex oligonucleotides (HDOs) conjugated to cholesterol or α-tocopherol at the 5' end of the RNA strand reach the CNS after subcutaneous or intravenous administration in mice and rats. The HDOs distribute throughout the brain, spinal cord and peripheral tissues and suppress the expression of four target genes by up to 90% in the CNS, whereas single-stranded ASOs conjugated to cholesterol have limited activity. Gene knockdown was observed in major CNS cell types and was greatest in neurons and microglial cells. Side effects, such as thrombocytopenia and focal brain necrosis, were limited by using subcutaneous delivery or by dividing intravenous injections. By crossing the blood-brain barrier more effectively, cholesterol-conjugated HDOs may overcome the limited efficacy of ASOs targeting the CNS without requiring intrathecal administration.

Histopathology Findings of the Lunate in Stage III Kienböck's Disease.

Background: The etiology and natural history of Kienböck's disease remain unclear. Traditionally it has been defined as avascular necrosis of the lunate. The authors tried to demonstrate different tissue distribution, the area ratio of necrotic tissue and vessel counts inside the whole Kienböck lunate to reveal a dynamic process of the lunate collapse. Methods: Five lunates from patients with stage III Kienböck's disease and one cadaveric lunate not involved by Kienböck's disease were sampled. They were sectioned, H&E stained, and evaluated. The thickness of trabecular bone and the area of necrotic tissue were measured with Image-Pro Plus. The number of vessels was counted manually. Results: In the normal lunate, the bone trabeculae showed a uniform distribution with fatty marrow filled the interspace between the trabeculae. In the lunates with Kienböck disease, the trabeculae fracture and necrosis located in the central part with massive fibrous granular tissue proliferation. There were also some chondroid metaplasia at the palmar and dorsal ends. The trabeculae of the lunates of the Kienböck's disease [0.188 mm (0.153 mm, 0.236 mm)] was significantly thicker than the normal lunates [0.146 mm (0.124 mm, 0.164 mm)]. The necrosis was localized around the fracture sites instead of the whole lunate. The mean necrosis area only accounts for 16.3% ± 8.9% of the whole section. Such kind of focal necrosis is quite similar to those around the traumatic fracture ends of other bones. Even in stage III Kienböck lunates, the vessels are quite abundant (221 ± 42 in one sagittal section), while the vessels inside the normal lunate were 352 ± 28. Conclusions: There is neither massive nor obvious generalized avascular bone necrosis in our histopathology observations. The focal necrosis and vessel damage were more likely associated with the broken trabeculae inside the lunate. Based on our histopathology observations, we suggested that the progressive process of Kienböck's disease could be described as lunate nonunion advanced collapse instead of avascular necrosis.

Isolation and characterization of a new goose orthoreovirus causing liver and spleen focal necrosis in geese, China.

Since July 2020, an infectious disease characterized by liver and spleen white focal necrosis has been spreading widely through geese farms in many regions of China. A novel goose orthoreovirus (GRV), designated GRV-GD2020, was isolated from the liver and spleen of dead geese. Phylogenetic analysis and sequence comparison revealed that all the genes of GRV-GD2020 clustered with other waterfowl-origin orthoreovirus. However, the gene constellation of GRV-GD2020 was not similar to that of any particular strain. Instead, the genomic segments of GRV-GD2020 showed 27.5-97.3% similarities to that of other waterfowl-origin orthoreovirus isolates. Waterfowl-origin orthoreovirus infections characterized by liver and spleen focal necrosis had not emerged in recent years. The re-emergence of the disease may be related to the recombination of the genome segments of Muscovy duck reovirus (MDRV), GRV, and new-type duck orthoreovirus. In summary, we determined that the GRV-GD2020 strain, causing goose liver and spleen focal necrosis, is a new variant of waterfowl-origin orthoreovirus.

Development of a Standardized Semantic Feature-Based Reporting Proforma for Intraoperative Ultrasound Findings in Brain Tumors and Application in High-Grade Gliomas - A Preliminary Study.

Purpose A semantic feature-based reporting proforma for intraoperative ultrasound findings in brain tumors was devised to standardize reporting. It was applied as a pilot study on a cohort of histologically confirmed high-grade supratentorial gliomas (Grade 3 and 4) for internal validation. Materials and Methods This intraoperative semantic ultrasound proforma was used to evaluate 3D ultrasound volumes using Radiant DICOM software by 3 surgeons. The ultrasound semantic features were correlated with histological features like tumor grade, IDH status, and MIB index. Results 68 patients were analyzed using the semantic proforma. Irregular crenated was the most common margin (63.2%) and lesions were heterogeneously hyperechoic (95.6%). Necrosis was commonly seen and noted as single (67.6%) or multiple (13.2%) in over 80% cases. A separate perilesional zone, which was predominantly hyperechoic in 41.8% and both hypo and hyperechoic in 12.7%, could be identified in 54.5% of cases. Grade 4 tumors were more likely to have an irregular crenated margin (71.2%) with a single large area of necrosis, while Grade 3 tumors were likely to have smooth (31.3%) or non-characterizable margins (31.2%) with no or multiple areas of necrosis. IDH-negative tumors were more likely to have a single large focus of necrosis. Among the GBMs (52 cases), MIB labelling index of>15% was associated with poorly delineated, uncharacterizable margins, when compared with MIB labelling index<15% (23.5 vs. 0%), (p=0.046). Conclusion A detailed semantic proforma was developed for brain tumors and was internally validated. A few ultrasound sematic features were identified correlating with histological features in high-grade gliomas. It will require further external validation for refinement and acceptability.

Reassessment of EWSR1 gene rearrangement-negative undifferentiated round cell sarcomas in bone and soft tissues by fluorescence in situ hybridization

Objective: To unravel the CIC rearrangement sarcomas and BCOR-CCNB3 sarcomas from EWSR1 rearrangement-negative undifferentiated round cell sarcomas in the bone and soft tissues. Methods: Twenty-eight cases of EWSR1 rearrangement-negative undifferentiated round cell sarcomas of bone and soft tissues, tested for CIC rearrangement and BCOR rearrangement by fluorescence in situ hybridization and related immunostaining were analyzed, and some of the BCOR rearrangement cases were verified by reverse transcription-polymerase chain reaction. Results: Five of 28 (17.9%) tested cases were positive for CIC rearrangement and six (21.4%) for BCOR rearrangement. Histopathologically, CIC rearrangement sarcomas comprised nodular aggregates of round to polygonal cells, containing hyperchromatic nuclei, prominent nucleoli and moderate cytoplasm, with focal variable necrosis and myxoid stroma. BCOR-CCNB3 sarcomas mostly comprised diffusely arranged, round to oval to short spindly cells with angulated nuclei, vesicular chromatin, inconspicuous nucleoli and interspersed vessels. Immunohistochemically, five of six BCOR-CCNB3 sarcomas showed CCNB3 immunostaining, which could be helpful for diagnosis. Two patients with CIC rearrangement sarcoma died of the diseases in seven months and twenty-two months. One patient with BCOR-CCNB3 sarcoma died of the diseases in forty-six months. Conclusions: Overall, 39.3% of the EWSR1 rearrangement-negative undifferentiated round cell sarcomas are CIC rearrangement sarcomas and BCOR-CCNB3 sarcomas. Molecular testing is helpful for diagnosis.

P-251 Multidisciplinary challenge for the oncologist and surgeon: Gastrointestinal stromal tumors. Follow-up of a tertiary surgical department

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in gastrointestinal system with most found in stomach. With the characteristic of being mostly c-KIT positive (CD117) as a mutation carrier, genetics is a part of the management of GIST, helping both the surgeon and the oncologist. The diagnosis and the definition of the characteristics of tumor will help to define the response to treatment procedures, which is fundamental for oncologists and surgeons to create an algorithm for their patients. The follow-up should be done both with oncologists and surgeons in order to define early recurrences and metastasis. This study is based on the follow-up of GIST patients operated in a tertiary general surgery department. 43 patients have been operated on between January 2017-December 2018. Routine preoperative diagnostic findings and postoperative pathological evaluations are identified and noted. In our hospital, routine management of GIST is as follows: In case of high grade GISTs, postoperative adjuvant imatinib therapy is routinely given for three years, and if there is metastasis or locally unresectable tumor, neoadjuvant imatinib treatment is given for shrinking the primary tumor and curing the systemic disease before the surgery. As the primary and golden treatment of GIST is surgery, surgery is always an option for even metastatic disease. Of 43 patients, 23 patients had a mitosis rate under 5/50, whereas 5 patients had a mitosis rate between 5/50 – 10/50, and 15 patients had a mitosis rate over 10/50. According to the size of the tumor, 3 patients had a single tumor under 2 cm. All of these three patients had lesions in the prepiloric area, and got operated with the symptoms of gastric outlet syndrome. 17 patients had a tumor between 2-5 cm, whereas 14 patients had a tumor between 5-10 cm. 9 patients had GIST tumors over 10 cm in diameter. Interestingly, all patients with liver metastasis had liver lesions over 10 cm. One patient with a tumor bigger than 10 cm had an extragastrointestinal stromal tumor, arising from the mesentery. The pathological results of the specimens were as follows: 29 spindle cell histologic subtype, 3 epitheloid cell subtype, and 11 mixed cell subtype. The focal necrosis was present in 14 patients. From 43 patients, three patients got reoperated. The first patient was reoperated at the fifth month postoperatively because of mechanical obstruction. The second patient got reoperated at the ninth month postoperatively because of incisional hernia. The third reoperated patient was reoperated because of the first pathological specimen was found out to be surgical borders millimetrically positive. The reoperation rate for our patients in three years of follow up was 6.97%. All reoperated patients had a pathological finding of spindle-cell type of morphology, with mitosis rates over 10/50. There needs to be more studies based on reoperation rates after GIST surgeries, but this study evaluated that complications after GIST surgery should be followed both by the oncologist and the surgeon.

Synergistic effects of sitagliptin and losartan against fipronil-induced hepatotoxicity in rats.

Background and Aim:Fipronil (FPN) is a potent pesticide that is heavily used around the world in agriculture. However, its irrational use could potentially have deleterious effects on animals and humans. The present study aimed to investigate the ability of sitagliptin (Sit) and losartan (LOS), when used both individually or concurrently, to guard rat liver against the acute hepatotoxicity caused by FPN.Materials and Methods:Forty-two adult male Wistar rats were equally divided into seven groups (6/group). Group I (control) received normal saline (0.5 mL/rat, vehicle for all treatments) by gavage once daily for 10 days. Group II received oral Sit (10 mg/kg body weight [BW]) daily for 10 days and Group III received oral LOS (5 mg/kg BW) daily for 10 days. Group IV received oral FPN (19.4 mg/kg BW; 1/5 of the oral LD50) for the past 5 days of the study. Groups V and VI received oral Sit (10 mg/kg BW) and LOS (5 mg/kg BW) daily, respectively, 5 days prior and 5 days during FPN administration (19.4 mg/kg BW). Group VII received oral Sit (10 mg/kg BW) and LOS (5 mg/kg BW) for 10 days with daily FPN during the past 5 days. After the end of the treatment period, the rats were humanely sacrificed and blood and liver tissue samples were collected for biochemical analysis and histopathological and immunohistochemical investigations.Results:FPN administration resulted in elevated alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase serum concentrations as well as increased malondialdehyde levels and reduced catalase, superoxide dismutase, glutathione peroxidase, and glutathione activity. The histopathological investigation showed disorganization of the hepatic cords and focal necrosis of the hepatocytes in FPN-intoxicated rats. Furthermore, the immunohistochemical examination showed that hepatic caspase-3 was overexpressed in the FPN-treated rats. The administration of Sit and LOS before and alongside FPN markedly mitigated the alterations caused by FPN and the hepatoprotective effects were more prominent in the combination group.Conclusion:Sit and LOS, both individually or in combination, confers considerable hepatoprotection against FPN-induced hepatotoxicity.

CALCIFICATION OF ARTERIES IN PATIENTS WITH ATHEROSCLEROSIS: CAUSES AND MECHANISMS OF DEVELOPMENT

The paper shows analogies between the mechanisms of calcification of arteries, various tissues and bone mineralization. In calcification the same mechanisms are involved, as at ossification of an organic matrix of a bone, including participation of stem cells. In the arteries and capillaries of various organs found polypotent precursors – mesenchymal stem cells, presumably responsible for the pathological mineralization of the arterial wall. Circulating in the blood and present in the intima of the human atheromatous aorta colony-forming stem cells of the stromal line of differentiation. Adventitia cells or pericytes are considered as a pluripotent mesenchymal reserve for replenishment of some cellular forms of connective tissue. Bone marrow stem cells of the stromal line of differentiation with the presence of pluripotent stromal cells in the blood and granulomas (plaques) and their transformation into bone tissue cells are involved in atherogenesis. Smooth muscle cells (SMCs) and myofibroblasts of the arterial wall adventitia have an osteoblast-like phenotype. Collagen and elastic fibers are involved in the calcification of blood vessels and soft tissues. Calcification of granulomas (plaques) accompanies their inflammatory morphogenesis, accompanied by the development of scar tissue. It often accompanies and completes the inflammation in them. This process is observed with the gradual replacement of the parenchyma of some organs with connective tissue. The mineral phase in bones and soft tissues, represented by calcium (Ca) and phosphate (P), contacts with nucleators - specific areas of collagen fibers. Non-collagen proteins are also involved in arterial calcification. With the progression of atherosclerosis and calcification of granulomas/plaques by cells present in the arterial wall, osteonectin is expressed. Osteopontin content is associated with Ca deposits in them; in particular, it correlates with the Ca level in the coronary arteries. In the processes of ossification and calcification, phosphatases play a certain role. In areas of calcification of granulomas/plaques, osteoprotegerin is found, which inhibits the activity of alkaline phosphatase in the aorta and prevents calcification of the media. Arterial wall calcification and inflammation are inhibited by fetuin-A and matrix γ-carboxyglutaric protein (MGP). The rate of bone formation and tissue calcification depends on the concentration of Ca and P in plasma and extracellular fluid. With their high concentration in the extracellular fluid, the mineral phase appears where it normally does not exist. Lipids are among the initiators of granuloma / plaque calcification in the arteries. The role of inflammation and necrosis in the calcification of the arteries is confirmed by experiments on animals with repeated intravenous injections of adrenaline, which causes focal necrosis of the middle membrane, which then undergoes calcification. In arterial walls, heart muscle, bone and cartilage tissue, osteonectin, osteocalcin, osteopontin, bone sialoprotein are often formed. In general, the mechanisms of arterial and soft tissue calcification are poorly understood. There are no effective remedies for calcification.

Female Adnexal Tumor of Probable Wolffian Origin

Female adnexal tumor of probable Wolffian origin (FATWO) often is a diagnostic challenge given its rarity, histologic heterogeneity, and lack of specific immunoprofile. To further understand the clinicopathologic and immunohistochemical features of this rare entity. We studied the clinical, morphologic, and immunohistochemical features of a cohort of 11 FATWO cases from our institute. Patients' age ranged from 25 to 76 years (mean, 55 years). Tumor size ranged from 0.5 to 18 cm (mean, 2.7 cm). Histopathologically, most tumors presented with low-grade cytologic features with low mitotic activity and lack of necrosis. Three main growth patterns were appreciated: solid, tubular, and sievelike patterns. Higher-grade nuclear atypia, increased mitotic activity, and focal necrosis were seen in 2 cases. These 2 cases were clinically considered malignant FATWO mainly because of their extra-adnexal involvement. Immunohistochemical studies found that tumor cells were positive for CD10 (11 of 11, 100%), AE1/3 (8 of 8, 100%), CAM 5.2 (4 of 5, 80%), and cytokeratin 7 (CK7; 7 of 10, 70%), and focally positive for calretinin (4 of 10, 40%), inhibin (4 of 10, 40%), epithelial membrane antigen (EMA; 3 of 9, 33%), and steroidogenic factor-1 (SF-1; 2 of 8, 25%). Lack of immunoreactivity to PAX8 and GATA3 in almost all cases indicates that FATWO is different from the tumors derived from the Müllerian or mesonephric origins. All patients with available follow-up had favorable prognosis. The broad spectrum of clinical presentation, various morphologic features, and overlapping immunophenotype suggest that FATWO is a diagnosis of exclusion until it is further defined at the molecular and immunohistochemical levels.

Novel duck reovirus exhibits pathogenicity to specific pathogen-free chickens by the subcutaneous route

To study the pathogenicity of new duck reovirus (NDRV) to chickens, eighty 3-day-old SPF chickens were equally divided into two groups. The experimental group was inoculated with a NDRV challenge strain of 100 μL (10–5.00 ELD50/0.1 mL) by the subcutaneous (s.c.) route, and the control group was inoculated with 100 μL of sterile phosphate-buffered saline (PBS) by the same route. In the experimental group, chickens exhibited introflexion of claws, performing of splits, stunting syndrome, weight loss and death. Gross lesions such as enlargement and yellowish-white focal necroses were observed in the liver and spleen. Microscopic changes were typical including varying degrees of hepatocyte steatosis and necrosis, splenic lymphocyte necrosis, interstitial pneumonia. Viral loads were detected in lung, liver, heart, spleen, duodenum, burse and kidney. The liver and spleen viral loads remained a much higher level and maintained for a longer time, suggesting that these tissues might be the target organs. In summary, NDRV can cause systemic infections and death in chickens, which indicated that chickens may be infected by NDRV in poultry production.

Effect of ionizing radiation on the secretion of the paracellular pathway in rat submandibular glands.

This study aims to investigate the effects of ionizing radiation on the secretion of the paracellular pathway in rat submandibular glands (SMGs) and reveal the changes in the tight junction (TJ) protein claudin-4. A total of 24 Wistar rats were randomly divided into control and irradiation groups. The irradiation groups were further divided into 1, 4, and 12 weeks groups after irradiation. One-time 20 Gy irradiation was given to the SMG area on the experimental side of the irradiation group. At 1, 4, and 12 weeks after irradiation, the secretion of SMGs was measured using the Schirmer's test. The pathological changes in the gland tissues were observed under light microscopy after hematoxylin⁃eosin (HE) staining. The changes in the TJ ultrastructure were observed under transmission electron microscopy. The immunofluorescence staining and Western blot were used to detect the expression levels of muscarinic acetylcholine M3 receptor, aquaporin 5 (AQP5), and claudin-4 protein. At 1, 4, and 12 weeks after irradiation, the secretion of SMGs in the irradiation group was significantly decreased and lower than that in the control group (P<0.01). At 1 week, the interstitial edema was observed in SMG tissues. Nuclear pyknosis, decreased number of acinar cells, and small focal necrosis with inflammatory infiltration were also observed over time. However, these changes were most evident at 12 weeks after irradiation. In the irradiation group, the TJ ultrastructure of glands at different times appeared to be fuzzy, collapsed, and had decreased electron density. Moreover, the width of TJs was remarkably decreased (P<0.01). The expression levels of M3 and AQP5 were decreased in a time-dependent manner, and the fluorescence intensity was significantly reduced after irradiation. However, the expression levels and fluorescence intensity of claudin-4 were enhanced in different degrees. The changes in the TJ structure, the upregulation of the claudin-4 expression, and the damage in the paracellular pathway were involved in the hyposecretion of SMGs after irradiation.