Absence Of Necrosis Research Articles

8774 An Uncommon Presentation Of A Large Silent Pheochromocytoma

Abstract Disclosure: M. Lozano: None. A. Pinero-Pilona: None. Background: The reported estimated incidence of pheochromocytoma is approximately 2-8 cases per 1 million people per year. Of those, silent pheochromocytomas will make up about 8%. Thus, biochemically silent and non-secreting pheochromocytomas are a very rare phenomenon. Clinical Case: A 74-year-old Caucasian female with significant past medical history of primary hypothyroidism, hypercholesterolemia, and nasal sinus carcinoma s/p surgery (in remission) presented to the clinic for endocrine evaluation of a right adrenal mass. The patient was asymptomatic and denied headaches, tachycardia, sweating, severe hypertension, diabetes, muscle weakness, easy bruising, or striae. The mass was initially diagnosed as an incidental finding after a contrast CT scan of the abdomen was performed for diverticulitis. The right adrenal enhancing mass was 2.3 x 3.9 x 4.1 cm in diameter. Subsequent MRI abdomen with and without contrast ordered by the referring physician showed that the adrenal mass had grown to 4.9 x 3.8 x 5.4 cm and was hyperenhancing in nature with central T2 hyperintense signal. Notably, multiple “parasitized and arborealized” vessels were detected within the mass. Such findings led us to suspect metastatic versus primary adrenal neoplasm such as cortical carcinoma as a working diagnosis. Other laboratory studies including plasma free metanephrines (<10 pg/mL, normal 0-88 pg/mL), plasma normetanephrines (29.2 pg/mL, normal 0-285.2 pg/mL) and 24-hour urine collections (24 hr urine epinephrine - 3 ug/24 hr [normal 0-20 ug/24 hr]; 24 hr urine norepinephrine - 75 ug/24 hr [normal 0-135 ug/24 hr]; 24 hr urine VMA - 3 mg/24 hr [normal 0-7.5 mg/24 hr]) were negative for pheochromocytoma. As her mass was greater than 4 cm in diameter, surgical referral was then recommended to the patient. Right adrenalectomy was performed. Pathology report was consistent with pheochromocytoma as supported by immunohistochemistry. Ki-67 proliferation index was 0-10% (average 3-4%, rare hotspots 10%). Atrophy and vascular ectasia were present in residual non-neoplastic adrenal cortex and medulla. Histology showed a nested growth pattern, absence of composite tumor elements, absence of necrosis, and no atypical mitoses. The incidence of non-secreting pheochromocytomas has been quoted to be 0.000064% (1). Conclusion: The case illustrates an uncommon presentation of a large, silent pheochromocytoma with negative plasma metanephrines accompanied by negative urine studies, which have a negative predictive value close to 100% in ruling out a pheochromocytoma. Our case emphasizes the importance of considering pheochromocytoma on the differential of adrenal masses with high attenuation or high enhancement even when biochemical studies suggest otherwise. Reference: (1) Radojkovic, D., et al. "CLINICALLY" SILENT GIANT PHEOCHROMOCYTOMA. CASE REPORT." Acta Endocrinologica (1841-0987) 9.1 (2013). Presentation: 6/1/2024

Diagnostic issues in neuroendocrine neoplasms ofthe lung.

Bronchopulmonary neuroendocrine neoplasms (BP-NENs) account for approximately 30% of all NENs. Although BP-NENs and NENs of the gastroenteropancreatic organs (GEP-NENs) share morphological and molecular features, they differ in terms of their terminology and classification. Bronchopulmonary neuroendocrine tumors (BP-NETs) have classically been termed as carcinoid and grouped into typical (TC) and atypical carcinoid (AC) based on the presence or absence of necrosis and mitotic count. In the most recent World Health Organization (WHO) classification for NENs of endocrine organs (WHO 2022), BP-NETs-NET G1 and G2-are introduced as synonyms of TC and AC, respectively. However, the Ki-67 index, which defines the grade of NETs in digestive organs, is only discussed in the descriptive text and not included into the criteria for classification of BP-NENs. In addition, well-differentiated NENs with high mitotic counts which correspond toNET G3 in the GEP organ system are not defined. This review discusses the role of Ki-67 for aproper classification of BP-NETs/carcinoids.

Metastatic Malignant Pseudomyogenic Hemangioendothelioma: An Exceedingly Rare Entity That Challenges Conventional Paradigms.

Pseudomyogenic hemangioendothelioma (PMHE), a rare soft tissue tumor predominantly affecting young adults, often presents as multiple nodules in various tissue planes of a limb. Malignant transformation and metastatic disease are unusual and pose diagnostic and therapeutic challenges. A 17-year-old patient from Western India, with a history of recurrent excisions for a toe swelling presented to our center for evaluation and management. A below-knee amputation was performed, and histopathology revealed PMHE. Adjuvant therapy was deemed unnecessary given the borderline nature of the tumor. Shortly thereafter, he developed features of local recurrence and underwent above-knee amputation. An expert histopathological review confirmed the diagnosis and noted features of malignant transformation-progression to a higher grade with greater cytological atypia, confluent growth, and increased mitotic activity over time. Upon further distant progression in the lung, he was started on a palliative regimen of weekly paclitaxel, vinblastine, and propranolol but eventually succumbed to his illness. In contrast to conventional descriptions of low mitotic activity, minimal nuclear atypia, and absence of necrosis, our patient exhibited increased mitotic rates, nuclear atypia, and evolving necrosis in serial histopathological evaluations. The fulminant clinical progression within a short interval was also atypical. Our patient's clinical course underscores the need for meticulous histopathological and molecular characterization and vigilant clinical surveillance after resection in patients with PMHE. Providing the standard of care for malignant disease in the adjuvant setting is challenging owing to the rarity and the lack of treatment guidelines.

In Vivo Histological Study Evaluating Non-Ablative Fractional 1940-nm Laser.

Non-ablative fractional lasers (NAFL) have increased in demand compared to ablative laser treatments as they provide lesser down time, fewer side-effects, and are safer to use. Non-ablative fractional treatment with lasers ranging from 1320 to 1927-nm have been shown to be safe and effective for skin resurfacing procedures. The objective of this study is to investigate healing of the 1940-nm NAFL-induced microthermal treatment zones (MTZs) in human skin from a histologic perspective. Three subjects received 1940-nm NAFL treatment to test areas on the abdomen at various timepoints during the study. The minimum 5 mJ/MTZ and maximum 20 mJ/MTZ energy settings were used at 20% coverage. Biopsies were taken coinciding with immediately posttreatment, 1, 3, 7 days, and 6 weeks posttreatment. Blinded analysis of hematoxylin and eosin stained slides was performed to measure the width and depth of the MTZs and evaluate the inflammatory and healing response of the skin over time (immediately to 6 weeks posttreatment). Safety was evaluated by assessing local skin responses and adverse events immediately after treatment and at all study visits. Histological analysis of tissue following NAFL 1940-nm treatments showed mild early inflammatory response (presence of lymphotic infiltrate) in some test areas and zones of necrosis and coagulation having widths and depths (immediately-3 days posttreatment) that scaled with the 1940-nm pulse energy. Signs of healing such as presence of dermal mucin, evidence of fibrosis, and absence of necrosis were observed long-term (7 days to 6 weeks posttreatment). Evidence of the MTZ persisted beyond the 6-week study and was predicted to last for 100 days. All local clinical skin responses healed within 6 weeks and were limited to mild, transient erythema and edema which resolved in less than 12-24 h following treatment. No serious adverse events occurred during the study. NAFL 1940-nm treatments are safe for inducing small fractional coagulation and necrosis zones in abdominal skin. NAFL 1940-nm laser creates fractional columns of injury with sufficient depth and coverage that suggest effective skin resurfacing, like other non-ablative fractional lasers.

Multiple cell death modalities and immune response in pulpitis.

To investigate the level and distribution of apoptosis, pyroptosis, necroptosis, and NETosis in pulpitis with or without necrosis on a basis of histological classification. Additionally, to examine the effect of pulpitis with necrosis (PWN) on the number and activation of peripheral and bone marrow (BM) neutrophils, as well as spleen lymphocytes, in a mouse model of pulpitis. The material comprised 20 permanent teeth, with or without caries, which were classified into three histological categories based on the distribution of inflammatory cells and the presence or absence of necrosis: (i) healthy pulp (HP), (ii) pulpitis without necrosis (PWON), and (iii) PWN. The levels of the four regulated cell death (RCD) pathways were detected by immunohistochemical and immunofluorescent staining with specific markers: apoptosis (caspase-8, cleaved caspase-3), pyroptosis (cleaved caspase-1, membrane-binding gasdermin D), necroptosis (receptor-interacting kinase 3, phosphorylated MLKL), and NETosis (myeloperoxidase, citrullinated histone H3). Acute pulpitis was induced in C57BL/6J mice via pulp exposure, and the mice were divided into four groups: (i) control (no tooth preparation, n = 6), (ii) Day 1 (sacrificed at 1 day after pulp exposure, n = 3), (iii) Day 3 (n = 3), and (iv) Day 5 (n = 7). The control and Day 5 groups were used for further immunofluorescent analysis to assess the levels of RCD and flow cytometry to monitor the changes in peripheral and BM neutrophils, as well as spleen lymphocytes. Human dental pulp stem cells (hDPSCs) were isolated and cultured from extracted healthy third molars. Apoptosis and necroptosis in hDPSCs were induced by staurosporine, whilst pyroptosis was induced by lipopolysaccharide and nigericin. One-way analysis of variance (ANOVA) with Tukey's test, Welch's ANOVA with Tamhane's test, and Student's t-tests were used to compare immunohistochemical labelling and flow cytometric data amongst groups (p < .05). The pulpal tissue of PWN can be divided into the abscess core (PWN-AC) and fibrous tissue (PWN-FT). The ratio of total necrotic cells (TUNEL-positive) in PWN-AC was significantly higher than in PWN-FT and PWON (both p < .01). Compared with HP, the expression levels of markers for apoptosis and pyroptosis were increased in PWON, whilst the expression levels of markers for apoptosis, pyroptosis, and NETosis were elevated in PWN, primarily detected in PWN-AC. Interestingly, myeloperoxidase (MPO) was exclusively observed in PWN-AC, with minimal detection in PWN-FT and PWON. Additionally, the frequency of MPO+ cells was significantly higher than that of MB-GSDMD+ cells and Cl-cas3+ cells in PWN-AC (both p < .01). Histological observation and TUNEL staining showed abundant necrotic cells in mouse pulpal tissue after pulp exposure, indicating a simulation of human PWN. In mouse pulpitis tissue, markers of apoptosis, pyroptosis, and NETosis were detected. Invitro, various cell deaths including apoptosis, pyroptosis, and necroptosis were also triggered in hDPSCs under various cell death treatments. Furthermore, in terms of systemic changes, pulp exposure-induced pulpitis could increase the number (p < .05) and cellular activity (p < .01) of neutrophils from BM in a mouse model. No significant changes in peripheral blood neutrophils, spleen T cells, B cells, or the CD4/CD8 ratio were detected between the control and pulpitis mice. Our findings uncover distinct patterns of mixed cell death at different histological stages of human pulpitis and the impact of pulpitis on the number and activity of BM neutrophils. Notably, NETosis occurs specifically and predominates in the abscess area of pulpitis, suggesting a potential effect of neutrophil extracellular traps (NETs) on pulpitis progression and NETs-targeted diagnostic strategy may play a role in decision making for vital pulp therapy.

Morphological MRI features as prognostic indicators in brain metastases

BackgroundStereotactic radiotherapy is the preferred treatment for managing patients with fewer than five brain metastases (BMs). However, some lesions recur after irradiation. The purpose of this study was to identify patients who are at a higher risk of failure, which can help in adjusting treatments and preventing recurrence.MethodsIn this retrospective multicenter study, we analyzed the predictive significance of a set of interpretable morphological features derived from contrast-enhanced (CE) T1-weighted MR images as imaging biomarkers using Kaplan–Meier analysis. The feature sets studied included the total and necrotic volumes, the surface regularity and the CE rim width. Additionally, we evaluated other nonmorphological variables and performed multivariate Cox analysis.ResultsA total of 183 lesions in 128 patients were included (median age 61 [31–95], 64 men and 64 women) treated with stereotactic radiotherapy (57% single fraction, 43% fractionated radiotherapy). None of the studied variables measured at diagnosis were found to have prognostic value. However, the total and necrotic volumes and the CE rim width measured at the first follow-up after treatment and the change in volume due to irradiation can be used as imaging biomarkers for recurrence. The optimal classification was achieved by combining the changes in tumor volume before and after treatment with the presence or absence of necrosis (p < < 0.001).ConclusionThis study demonstrated the prognostic significance of interpretable morphological features extracted from routine clinical MR images following irradiation in brain metastases, offering valuable insights for personalized treatment strategies.

Management of typical and atypical metastatic lung carcinoids: present and future perspectives.

Lung carcinoids are rare tumors representing 1-2% of all invasive lung malignancies. They include typical and atypical carcinoids, whose distinction is made based on the mitotic index and presence or absence of necrosis. The 10-year overall survival for stage IV typical carcinoid is 47% and 18% for atypical carcinoid, reflecting the indolent growth of these tumors. There are limited approved treatment options for them and most of the evidence comes from retrospective analyses, single-arm trials, subgroup analysis of phase II/III trials for metastatic neuroendocrine tumors and extrapolation of data from phase III trials for gastroenteropancreatic neuroendocrine tumors. Management of metastatic lung carcinoids requires a multidisciplinary standardized approach in specialized centers. Treatment should have a dual objective, control of tumor growth and control of symptoms related to hypersecretion syndromes, aiming to improve quality of life and survival. In the continuum of treatment disease, locoregional treatment options need to be considered in parallel with systemic treatments. In this paper, we review the present treatment options and their rational and we give an insight into future alternatives.

Preoperative differentiation of gastric schwannomas and gastrointestinal stromal tumors based on computed tomography: a retrospective multicenter observational study.

Gastric schwannoma is a rare benign tumor accounting for only 1-2% of alimentary tract mesenchymal tumors. Owing to their low incidence rate, most cases are misdiagnosed as gastrointestinal stromal tumors (GISTs), especially tumors with a diameter of less than 5 cm. Therefore, this study aimed to develop and validate a diagnostic nomogram based on computed tomography (CT) imaging features for the preoperative prediction of gastric schwannomas and GISTs (diameters = 2-5 cm). Gastric schwannomas in 47 patients and GISTs in 230 patients were confirmed by surgical pathology. Thirty-four patients with gastric schwannomas and 167 with GISTs admitted between June 2009 and August 2022 at Hospital 1 were retrospectively analyzed as the test and training sets, respectively. Seventy-six patients (13 with gastric schwannomas and 63 with GISTs) were included in the external validation set (June 2017 to September 2022 at Hospital 2). The independent factors for differentiating gastric schwannomas from GISTs were obtained by multivariate logistic regression analysis, and a corresponding nomogram model was established. The accuracy of the nomogram was evaluated using receiver operating characteristic and calibration curves. Logistic regression analysis showed that the growth pattern (odds ratio [OR] 3.626; 95% confidence interval [CI] 1.105-11.900), absence of necrosis (OR 4.752; 95% CI 1.464-15.424), presence of tumor-associated lymph nodes (OR 23.978; 95% CI 6.499-88.466), the difference between CT values during the portal and arterial phases (OR 1.117; 95% CI 1.042-1.198), and the difference between CT values during the delayed and portal phases (OR 1.159; 95% CI 1.080-1.245) were independent factors in differentiating gastric schwannoma from GIST. The resulting individualized prediction nomogram showed good discrimination in the training (area under the curve [AUC], 0.937; 95% CI, 0.900-0.973) and validation (AUC, 0.921; 95% CI, 0.830-1.000) datasets. The calibration curve showed that the probability of gastric schwannomas predicted using the nomogram agreed well with the actual value. The proposed nomogram model based on CT imaging features can be used to differentiate gastric schwannoma from GIST before surgery.

Application experience of bioresorbable implants in correcting the volume of the pleural cavity and their biocompatibility assessment

Objective: To substantiate experimentally the possibility of using bioresorbable biopolymer pleural implants made of polylactide and polycaprolactone (PLA/PCL) to correct the volume of the chest. Materials and methods. Rabbits were used as experimental animals — mature females of the Chinchilla breed, age 1–1.5 years, weight 3500–4300 g. The number of individuals were 5. For studying changes in implants and local tissue reactions in vivo, as close as possible to clinical conditions, the method of intrapleural implantation was used. Bio-resorbable highly porous samples based on polylactide and polycaprolactone (PLA/PCL) with different polymer ratios and porosity degrees were used as implants. The implant and local tissue reactions were evaluated over five implantation periods: 7, 21, 54, 66 and 78 weeks. Results. The study of morphology in implants during a long experiment showed good biocompatibility, which was confirmed by the absence of necrosis in implants and surrounding tissues. In the first and second implantation periods minimal reactive changes were detected in the adjacent soft tissues (lung, pleura, soft tissues of the chest wall), existing as a focal fibrosis of muscle fibers, focal mononuclear infiltration of fibrous tissue. Conclusion: As a result of studying morphological changes in the implant and adjacent tissues of the chest wall, the absence of necrosis and purulent-inflammatory changes both in the implant itself and in the surrounding tissues of the chest wall and lung was confirmed. It has been proven that a highly porous pleural implant based on polylactide and polycaprolactone is a safe and promising material for correcting the volume of the chest, which can be in demand both in general thoracic surgery and for the surgical treatment of patients with advanced pulmonary tuberculosis.

Immunohistochemical expression of cytochrome P4A11 (CYP4A11), carbonic anhydrase 9 (CAIX) and Ki67 in renal cell carcinoma; diagnostic relevance and relations to clinicopathological parameters

BackgroundCytochrome P4A11 (CYP4A11) is a member of cytochrome p450 family, which is involved in arachidonic acid metabolism that participates in promoting malignant cell proliferation, progression, and angiogenetic capacity. Carbonic Anhydrase 9 (CAIX) is a transmembrane protein that plays an integral part in regulating hypoxia which affects cancer cell metabolism, proliferation and promotes metastasis. The aim of this study was to evaluate the immunohistochemical expression of CYP4A11, CAIX and ki67 in RCC subtypes in relation to clinicopathological parameters and to evaluate the diagnostic significance of CYP4A11 and CAIX in differentiating renal cell carcinoma (RCC) subtypes. Materials and methodsone hundred primary RCC cases, collected from Pathology Department, Faculty of Medicine, Tanta University and from private laboratories, were evaluated for immunohistochemical expression of CYP4A11, CAIX and ki67. ResultsCYP4A11 was expressed in 59% of RCC; with 91.7% sensitivity and 90% specificity in differentiating clear cell and non-clear cell subtypes. CAIX was expressed in 50% of RCC; with 95% sensitivity, 80% specificity. High expression of CYP4A11 was statistically positively associated with higher tumor grade, high expression of CAIX was statistically positively associated with lower tumor grade and absence of necrosis and high ki67 labeling index was significantly associated with clear cell subtype, larger tumor sizes, higher tumor grade, advanced tumor stage, fat invasion and vascular invasion. ConclusionsCYP4A11 and CAIX can be used as diagnostic markers to differentiate clear cell RCC from other subtypes. CYP4A11 is more diagnostically accurate and specific than CAIX. High expression of CYP4A11, low CAIX expression and high ki67 labeling index were related to features of aggressive tumor behavior.

Hypoxia-inducible factor 2α protein and mRNA expression correlate with histomorphological features in clear cell renal cell carcinoma

Hypoxia-inducible factor 2α (HIF2α) has been identified as a potential biomarker and novel target for systemic therapy in clear cell renal cell carcinoma (ccRCC). The present study aims to evaluate the association of HIF2α protein and HIF2A mRNA expression with clinicopathological factors and histomorphological features related to vasculature and inflammation of ccRCC using a localized ccRCC cohort (n = 428) and The Cancer Genome Atlas (TCGA)-KIRC cohort (n = 433). HIF2α protein expression was immunohistochemically assessed using tissue microarrays and HIF2A mRNA expression was assessed using the TCGA RNA-sequencing data. Positive HIF2α protein and high HIF2A mRNA expression were observed in 145 (33.9 %) and 142 (32.8 %) patients, respectively. Positive nuclear HIF2α protein expression was significantly associated with the clear histological phenotype and architectural patterns related to rich vascular networks (p < 0.001), and no tumor-associated immune cells status (p < 0.05) in addition to favorable prognostic factors such as lower TNM stage, lower WHO/ISUP grade, or the absence of necrosis (p < 0.001). The HIF2A mRNA expression profile by the TCGA cohort showed similar trends as the HIF2α protein profile. In addition, positive HIF2α protein and high HIF2A mRNA expression were associated with higher recurrence-free survival and overall survival, respectively (both p < 0.001). In conclusion, we comprehensively demonstrated the association of HIF2α profiles with clinicopathological factors and histomorphological features related to vasculature and inflammation at both protein and mRNA levels. Histomorphological features expressing HIF2α may provide information on HIF2α targeted therapeutic response as well as prognosis in ccRCC patients.

Thyroid transcription factor‐1 expression in lung neuroendocrine tumours: a gender-related biomarker?

PurposeThyroid transcription factor‐1 (TTF‐1) assessed by immunohistochemistry (IHC) is a specific biomarker for lung adenocarcinoma, and is commonly used to confirm the pulmonary origin of neuroendocrine tumours (NET). The majority of the available data suggest that TTF-1 is favourable prognostic biomarker for lung adenocarcinomas, whereas its role is more conflicting for lung NET. The main aim of this multicenter retrospective study was to investigate the potentially relevant associations between TTF-1 biomarker and clinical and pathological features of the study population, as well as determine TTF-1 prognostic effect on the clinical outcome of the patients.MethodsA multicentre retrospective study was conducted on 155 surgically-removed lung NET, with available IHC TTF-1 assessment.ResultsMedian age was 59.5 years (range 13–86), 97 patients (62.6%) were females, 31 cases (20%) were atypical carcinoids, 4 (2.6%) had TNM stage IV. Mitotic count ≥2 per 10 high-power field was found in 35 (22.6%) subjects, whereas necrosis was detected in 20 patients (12.9%). TTF-1 was positive in 78 cases (50.3%). The median overall survival was 46.9 months (range 0.6–323) and the median progression-free survival was 39.1 months (range 0.6–323). Statistically significant associations were found between (1) TTF-1 positivity and female sex (p = 0.007); and among (2) TTF-1 positivity and the absence of necrosis (p = 0.018).ConclusionsThis study highlights that TTF-1 positivity differs according to sex in lung NET, with a more common TTF-1 positive staining in female. Moreover, TTF-1 positivity correlated with the absence of necrosis. These data suggest that TTF-1 could potentially represent a gender-related biomarker for lung NET.

Abstract P3063: Selective Release Of Mitochondrial Dna After Brief Myocardial Ischemia

Objective: Mitochondrial DNA (mtDNA) is one of several pro-inflammatory damage-associated molecular patterns released from necrotic myocytes during myocardial infarction (MI). Based on our recent observation of a ~50-fold rise in circulating mtDNA after brief whole-body ischemia in a porcine model of cardiac arrest without ongoing MI, we hypothesized that ischemia-induced mtDNA release can occur in the absence of necrosis. Accordingly, we measured circulating mtDNA levels before and after localized myocardial ischemia of insufficient duration to produce myocyte necrosis in swine. Methods: Swine (n=6) were subjected to a 10-minute occlusion of the left anterior descending (LAD) coronary artery based on prior evidence that this duration of ischemia elicits myocardial injury without necrosis. Peripheral venous and coronary sinus (CS) blood samples collected at baseline (BL) as well as 1-hour and 24-hours after reperfusion were analyzed via qPCR to quantify mtDNA and nuclear DNA (nucDNA) release. Results were compared to a separate group of swine (n=6) subjected to a 75-minute LAD occlusion to produce MI. Results: Prolonged ischemia led to a significant rise in CS levels of mtDNA (6.2 ± 3.6-fold vs. BL; p&lt;0.05) and nucDNA (5.4 ± 2.0-fold vs. BL; p&lt;0.05) 1 hour after reperfusion, consistent with rapid non-selective DNA release after myocyte necrosis. In contrast, brief ischemia was associated with detectable elevations in CS mtDNA (4.6 ± 1.4-fold vs. BL; p&lt;0.05) but not nucDNA (2.1 ± 0.5-fold vs. BL; p=0.35) at this timepoint. However, the magnitude of DNA release after brief or prolonged ischemia was not sufficient to increase circulating mtDNA or nucDNA, as peripheral venous levels of mtDNA and nucDNA did not differ from BL at 1-hour or 24-hours post-reperfusion in either group. Conclusion: Brief myocardial ischemia is associated with selective release of mtDNA into circulation, providing a potential mechanism by which immune activation may occur after myocardial injury even when myocyte necrosis is absent. The magnitude of mtDNA release after brief myocardial ischemia is ~10-fold lower than that detected in peripheral blood after resuscitation from cardiac arrest, suggesting that mtDNA is released from other organs after brief whole-body ischemia.

Macro and microscopic characteristics of the placenta and its relationship with the weight and the Apgar score of canine neonates

The placenta is the main organ of pregnancy and is directly related to the proper development of the fetus. The correlation among some placental measurements and their respective neonates is widely studied in the human species. However, the studies regarding bitches are still limited. Therefore, the aim of this work was to evaluate if there is a relationship between placental weight and volume and the weight of neonates at birth in the canine species, as well as its influence on their viability. In this work, 7 bitches, 18 neonates and their placentas were evaluated. The weight of the placentas was measured using an analytical balance and the volume was calculated by measuring the volume of water displaced after placing it in a container of water. The neonates were weighed and classified according to the Apgar score after birth. Samples from each placenta were fixed in formalin and embedded in paraffin, then placed on slides and stained in hematoxylin and eosin. From these samples, the microvascular density (MVD) was calculated, as well as the presence or absence of necrosis, calcification and haemorrhage, classified in scores from 0 to 2. Data were analyzed using Kendall's test. The mean weight of the placentas was 29.11 ± 11.06 g and the volume was 21.33 ± 10.65 cm³. The mean weight of the neonates was 282.94 ± 123.28 g and the Apgar score was 8.83 ± 2.06. The mean MVD of the placentas was 0.04 ± 0.01. A positive correlation was observed between birth weight and placental weight and volume. Placental weight also positively correlated with placental volume. Also, no significant correlation was found between MVD and alterations with placental weight and volume and with the weight and Apgar score of neonates. Among the microscopic changes, only necrosis showed a moderate correlation with placental weight and volume. It can be concluded that the placenta has an influence on the weight of neonates, which is essential for its development in intra and extrauterine life. However, more studies are required in the described species, to better elucidate these questions.

Новые биосинтетические имплантаты для хирургического лечения туберкулеза легких

Experimental testing of biocompatible biodegradable highly porous pleural implants for the surgical treatment of destructive pulmonary tuberculosis. Laboratory animals were implanted with a highly porous biorsorbable material based on polylactide and polycaprolactone. The morphological picture in implants and in local tissues was studied after intrapleural implantation at 7, 21, 54, 66 and 78 weeks, the animals were removed from the experiment by overdosing of drugs for anesthesia. As experimental animals, rabbits were used- mature females of the Chinchilla breed, age 1–1.5 years, body weight 3500–4300 g. When studying the morphological picture in the implants, good biocompatibility was observed during a long experiment, which was manifested by the absence of necrosis in the implants and surrounding tissues. In implants, a capsule is formed over time, starting from week 7, the processes of implant vascularization occur, which begin with the surface sections with the development of small capillary-type vessels, followed by the ingrowth of vessels into the thickness of implants and the formation of larger thin-walled sinusoidal vessels, as well as larger vessels (arteries and veins), in addition to capillaries. In the adjacent soft tissues (lung, pleura, soft tissues of the chest wall) in the first and second implantation periods, reactive changes are minimal. They manifest as focal fibrosis of muscle fibers, focal mononuclear infiltration in fibrous tissue in the first implantation period (7 weeks). And in the form of weakly expressed cellular infiltration in separate fields of vision in adjacent soft tissues in the second period. Upon further examination, no perifocal changes were observed in the third, fourth and fifth transplantation periods. Morphological changes were studied in the implant and adjacent tissues of the chest wall. It is proved that a highly porous pleural implant based on polylactide and polycaprolactone has good biocompatibility and bio-safety, is a promising material for general thoracic surgery and surgical treatment of destructive widespread pulmonary tuberculosis.

Hepatoprotective activity of Tridecan-1-ol isolatedfrom Flaveria trinervia (Speng). C. Mohr

Background- Flaveria trinervia (Asteraceae), a medicinal herb has been used in Indian traditionl medicine to cure jaundice. Reports on phytochemical and pharmacological investigations are very scarce. A phytoconstiuent Tridecan-1-ol and screened for hepatoprotective activity. -To evaluate hepatoprotective effects of Tridecan-1-ol against CCl4 induced hepatic damage on Wister albino rats. Methods- Tridecan-1-ol was isolated from petroleum extract of Flaveria trinervia using silica gel column chromatography and the structure was confirmed by IR, MASS,and 1H NMR spectroscopic studies. The parameters employed to confirm the hepatoprotectivity were the estimation of liver function serum markers such as total bilirubin, total protein, alanine transaminase, aspartate transaminase, alkaline phosphatase activities and the histological profile of the liver tissue. Results-The LD50 of petroleum ether extract and the constituent Tridecan -1-ol was found to be 500 and 150 mg/kg body weight respectively. Tridecan -1-ol showed significant hepatoprotective activity than the crude extract and it was compared with the standard hepatoprotective drug silymarin. The histological profile of the liver tissue ofTridecan-1-ol administered rats showed the presence of normal hepatic cords, absence of necrosis and fatty infiltration as similar to the controls. Conclusion-Tridecan-1-ol afforded significant hepatoprotectivity against CCl4 induced liver damage and supported the traditional claim of Flaveria trinervia as a hepatoprotective herb.

Hepatoprotective Activity of 6-Heptadecylcyclohex -3-ene-1 Carboxylic Acid Isolated from the Methanol Extract of Dichrostachys cinerea Wight &amp; Arn. Stem Bark

Aim of the Study: The phytoconstituent 6-heptadecylcyclohex 3-ene-1 carboxylic acid isolated from the methanol extract of Dichrotachys cinerea Wight. stem bark was evaluated for hepatoprotective activity against CCl4 induced toxicity.&#x0D; Materials and Methods: The constituent 6-heptadecylcyclohex 3-ene-1 carboxylic acid isolated from the methanolic extract of D. cinerea and the structure was confirmed by spectroscopic studies. Hepatoprotective property was screened in male wistar strain rats. The parameters studied were estimation of liver function serum markers such as serum total bilirubin, total protein, alanine transaminase, aspartate transaminase, alkaline phosphatase and histological profile of the liver tissue.&#x0D; Results: The LD50 of methanolic extract and constituent, 6-Heptadecylcyclohex -3-ene-1 carboxylic acid were evaluated and found to be 500 and 100 mg/kg body weight respectively. The hepatoprotective activity of constituent was more significant as similar to the standard hepatoprotective drug silymarin. The histological profile of the liver tissue showed the presence of normal hepatic cords, absence of necrosis and fatty infiltration as similar to the controls.&#x0D; Conclusion: The methanolic extract of D. cinerea stem bark and the phytoconstituent 6-heptadecylcyclohex-3-ene-1 carboxylic acid showed significant protection from CCl4 induced liver damage.

Evaluation of factors predicting postoperative recurrence and metastasis of parathyroid cancer: a single-center study

PurposeThe purpose of this study was to examine the postoperative clinical course of parathyroid carcinoma to determine factors that predict postoperative recurrence and distant metastasis.MethodsIn this retrospective study, we included 38 patients with parathyroid carcinoma who received surgical intervention at Itoh Hospital between 1979 and 2020. Clinicopathologic characteristics (age, sex, intact PTH, serum Ca level, operation type, parathyroid weight, parathyroid size, histopathologic findings: vascular invasion, capsular invasion, necrosis, histological type, and Ki-67 staining) were used. The median follow-up observation period was 63.7 months.ResultsPostoperatively, 5 patients (13.2%) developed distant metastasis or had localized recurrence, and 3 patients died (7.9%). The results of the univariate analysis revealed three factors affecting distant metastasis and recurrence, which were Ki-67 (p = 0.0041), the presence or absence of necrosis (p = 0.0163), and tumor weight (p = 00,189). Using the cutoff values obtained by ROC analysis, which were 4.1 for Ki-67 (sensitivity of 80% and specificity of 96.9%) and 4890 mg for tumor weight (sensitivity of 100% and specificity of 60.9%), we calculated the cumulative incidence of recurrence and distant metastasis by the three factors retained. We found that the presence of the three factors was associated with a high possibility of distant metastasis or recurrence during the 5-year follow-up period.ConclusionsThree factors, Ki-67, necrosis, and tumor weight in parathyroid carcinoma, may predict outcomes of postoperative recurrence and distant metastasis.

Embryo-hepatotoxic Potential of Spearmint Aqueous Extracts: A Histopathological Study

Introduction: Spearmint, a member of lamiacae family, used in home remedies for the treatment of respiratory, GIT and other diseases.&#x0D; Aims &amp; Objectives: To observe the effects of spearmint aqueous extract on liver histology in Swiss albino mice pups. Place and duration of study: The current experimental study was carried out in the Anatomy Department, Shaikh Zayed PGMI, Lahore over a period of 6 months.&#x0D; Material and Methods: Adult mice (Swiss Albino mice) were used (7 male and 21 female). Female mice were divided and labeled into control group (A) and two experimental group i.e. low dose (B) and high dose (C) after conception; all these groups had 7 mice each. Distilled water was given to group A and leaves extract of spearmint was given to group B and C in doses of 3 &amp; 6g/kg per day, respectively. After completion of pregnancy the pups were delivered by hysterotomy out of which 28 mice pups were randomly selected and marked as control/A1, low dose/B1 and high dose/C1 groups, respectively. The liver of all pups was dissected, slides made, and hepatocytes were examined for their shape, presence or absence of necrosis and vacuolization. Data was analyzed using SPSS software version 20.0,P- value&lt;0.05 was taken as significant.&#x0D; Results: Shape of hepatocytes was unchanged, but vacuoles and necrosis found in livers of freshly delivered pups with p-value &lt;0.001whose mothers had received spearmint treatment during pregnancy. Difference among both spearmints treated groups was significant and p-value was 0.026.&#x0D; Conclusion: Spearmint aqueous extracts administered to female mice during pregnancy in both low and high doses carry embryo hepatotoxic potential with in utero harmful effects on swiss albino mice pup offspring.

Caracterização de coccidiose e avaliação de casos sugestivos de enterite necrótica subclínica em frangos de corte

ABSTRACT: This study performed the characterization of coccidiosis in broilers and evaluated the occurrence of suggestive cases of necrotic enteritis (NE), seeking if there is an association between the diseases in Brazilian flocks. Two hundred and fifty-six birds from 32 flocks were evaluated. Macroscopic and histopathological lesions were graduated for coccidiosis and NE. Intestinal content was investigated by polymerase chain reaction (PCR) for seven species of Eimeria and by selective anaerobic culture for Clostridium perfringens and identification of the NetB gene. Flocks positive for coccidiosis represented 93.8%. Macroscopic lesions of coccidiosis were Grade 1 for E. acervulina (27%); E. tenella (9.7%) and E. maxima (8.9%). Histopathological evaluation showed Grade 1 in duodenum (38.2%); jejunum (21.4%); cecum (9.3%) and ileum (5%). PCR demonstrated positivity for E. tenella (21.9%), E. maxima (18.8%), and E. acervulina (3.1%). Suggestive macroscopic lesions of necrotic enteritis ranged from Grade 1 (16%), 2 (23%) and 3 (10,9%). Histopathology indicated the absence of necrosis, showing only hemorrhage in the mucosa and submucosa, with the presence of Eimeria spp. Clostridium perfringens type A netB+ was not isolated, demonstrating that macroscopic lesions found mostly in the jejunum did not characterize NE, based on histopathology and negativity of the NetB gene. The study suggests that, due to the high occurrence of coccidiosis, many macroscopic findings suggestive of NE are, in fact, attributed to atypical lesions caused by the reproduction of Eimeria spp.