Massive Necrosis Research Articles

Necrotizing Follicular Lymphoma of the Inguinal Region with Sternbergoid Cells: Clinical–Pathological Features of a Challenging Entity

Follicular lymphoma (FL) is one of the most common B-cell malignancies worldwide. While the diagnosis of conventional cases is straightforward, rare clinical–pathological variants may be challenging due to their misleading morphology, aberrant phenotype and/or atypical presentation. To add to the spectrum of unusual FLs, we report on a rare disease pattern characterized by (i) inguinal presentation, (ii) massive necrosis, (iii) Hodgkin/Reed–Sternberg (HRS)-like cells, and (iv) adjacent areas of diffuse large B-cell lymphoma evolution. All cases occurred in elderly patients (median age at diagnosis: 69.5 years), disclosed a low stage at diagnosis (Ann Arbor stage IA-IIA), and had deceiving clinical features. Despite the alarming histology, excellent responses to conventional therapies were reported in all patients. In conclusion, necrotizing FL of the inguinal region is a rare neoplasm characterized by peculiar clinical and histological features. This lymphoma should always be considered in the differential diagnosis of massively necrotic inguinal lesions.

Black TiO2 nanoprobe-mediated mild phototherapy reduces intracellular lipid levels in atherosclerotic foam cells via cholesterol regulation pathways instead of apoptosis

Given that apoptosis increases the risk of plaque rupture, strategies that reduce intracellular lipid levels without killing foam cells are warranted for safe and effective treatment of atherosclerosis. In this study, a mild phototherapy strategy is carried out to achieve the hypothesis. Foam cell-targeted nanoprobes that allow photothermal therapy (PTT) and/or photodynamic therapy (PDT) were prepared by loading hyaluronan and porphine onto black TiO2 nanoparticles. The results showed that when temperatures below 45 °C, PTT alone and PTT + PDT significantly reduced the intracellular lipid burden without inducing evidently apoptosis or necrosis. In contrast, the use of PDT alone resulted in only a slight reduction in lipid levels and induced massive apoptosis or necrosis. The protective effect against apoptosis or necrosis after mild-temperature PTT and PTT + PDT was correlated with the upregulation of heat shock protein 27. Further, mild-temperature PTT and PTT + PDT attenuated intracellular cholesterol biosynthesis and excess cholesterol uptake via the SREBP2/LDLR pathway, and also triggered ABCA1-mediated cholesterol efflux, ultimately inhibiting lipid accumulation in foam cells. Our results offer new insights into the mechanism of lipid regulation in foam cells and indicate that the black TiO2 nanoprobes could allow safer and more effective phototherapy of atherosclerosis.

Liver Progenitor Cells in Massive Hepatic Necrosis-How Can a Patient Survive Acute Liver Failure?

Massive hepatic necrosis is the most severe lesion in acute liver failure, yet a portion of patients manage to survive and recover from this high-risk and harsh disease syndrome. The mechanisms underlying recovery remain largely unknown to date. Recent research progress highlights a key role of liver progenitor cells, the smallest biliary cells, in the maintenance of liver homeostasis and thus survival. These stem-like cells rapidly proliferate and take over crucial hepatocyte functions in a severely damaged liver. Hence, the new findings not only add to our understanding of the huge regenerative capability of the liver, but also provide potential new targets for the pharmacological management of acute liver failure in clinical practice.

Histologic Analysis of Transjugular Liver Biopsy Specimens for Early Prediction of Prognosis in Acute Liver Failure.

The prognosis of acute liver failure (ALF) treated with conservative therapy is extremely poor. Histologic diagnosis at the time ALF occurs provides important clues for determining the prognosis, including indications for liver transplant. Transjugular liver biopsy (TJLB), which helps clarify the pathology of ALF, may be an effective clinical parameter that contributes to prognosis prediction, including indications for liver transplant. In this prospective study, 79 patients who underwent TJLB with ALF were enrolled between May 2002 and March 2021. The relationships between prognosis and the extent of tissue necrosis on TJLB specimens, serum parameters related to the cause, and clinical parameters were investigated. Model for end-stage liver disease-sodium, hepatic encephalopathy predicting, total bilirubin, hepatocyte growth factor, ammonia, coma rate, and histologic diagnosis were identified as prognostic factors on univariate analysis. Histologically, 13 of 16 patients with massive hepatic necrosis died or had a liver transplant. On multivariate analysis, the only prognostic factor was massive hepatic necrosis. There were no treatment-related complications, and TJLB was technically successful in all patients. In diagnosing the cause of ALF and understanding its pathology, TJLB contributes to predicting the prognosis of ALF based on histologic findings together with liver function tests and imaging findings, and it is an important diagnostic technique for determining diagnostic and treatment eligibility, including indications for liver transplant. When determining the best timing for patient selection and liver transplant, the finding of massive hepatic necrosis on TJLB specimens at the time ALF occurred was the most important prognostic factor.

Malignant oligoastrocytoma in the spinal cord of a cat.

A 12-year and 3-month spayed female mixed cat was presented with severe lumbar pain. Magnetic resonance imaging and postmortem examination revealed a swollen lesion in the spinal cord at L3 level. Histologic examination identified extensive neoplastic cell proliferation with massive necrosis in the tumor tissue. Two types of neoplastic cells were recognized. One type of neoplastic cells were large cells characterized by round to polygonal shape and abundant eosinophilic cytoplasm (referred to as “large cells”). The other neoplastic cells were small, densely proliferated, and had round to irregular shape and scant eosinophilic cytoplasm (referred to as “small cells”). Both types of cells were positive for oligodendrocyte transcription factor 2 and SRY-box transcription factor 10. Glial fibrillary acidic protein was positive in large cells but negative in most small cells. Digital analysis for Ki-67-stained tumor tissues found that total 21.1% ± 6.5% of tumor cells were positive for Ki-67. Based on these findings, we diagnosed malignant oligoastrocytoma in the spinal cord.

Neutrophil Extracellular Traps Mediate Acute Liver Failure in Regulation of miR-223/Neutrophil Elastase Signaling in Mice.

Background & AimsMarked enhancement of neutrophil infiltration in the liver is a hallmark of acute liver failure (ALF), a severe life-threatening disease with varying etiologies. However, the mechanisms and pathophysiological role corresponding to hepatic neutrophil infiltration during ALF development remain poorly characterized.MethodsExperimental ALF was induced in 10-week-old male microRNA-223 (miR-223) knockout (KO) mice, neutrophil elastase (NE) KO mice, and wild-type controls by intraperitoneal injection of galactosamine hydrochloride and lipopolysaccharide. Age-matched mice were injected with phosphate-buffered saline and served as vehicle controls.ResultsMouse liver with ALF showed evident formation of neutrophil extracellular traps (NETs), which were enhanced markedly in miR-223 KO mice. The blockade of NETs by pharmacologic inhibitor GSK484 significantly attenuated neutrophil infiltration and massive necrosis in mouse liver with ALF. ALF-related hepatocellular damage and mortality in miR-223 KO mice were aggravated significantly and accompanied by potentiated neutrophil infiltration in the liver when compared with wild-type controls. Transcriptomic analyses showed that miR-223 deficiency in bone marrow predominantly caused the enrichment of pathways involved in neutrophil degranulation. Likewise, ALF-induced hepatic NE enrichment was potentiated in miR-223 KO mice. Genetic ablation of NE blunted the formation of NETs in parallel with significant attenuation of ALF in mice. Pharmaceutically, pretreatment with the NE inhibitor sivelestat protected mice against ALF.ConclusionsThe present study showed the miR-223/NE axis as a key modulator of NETs, thereby exacerbating oxidative stress and neutrophilic inflammation to potentiate hepatocellular damage and liver necrosis in ALF development, and offering potential targets against ALF.

Comprehensive treatment of gunshot wounds using vacuum therapy and technomolecular silver preparations

Introduction. Burn wounds from the moment of their occurrence are primarily infected, and are accompanied by a violation of microcirculation, which contributes to the formation of massive necrosis of soft tissues, and leads to the delayed healing of such wounds. The speed of wound healing depends on a number of factors, not least of which is local treatment. An effective solution to this problem is the use of vacuum therapy (Vacuum Assisted Closure), which in combination with technomolecular silver preparations improves the course of all phases of the wound process, promotes active drainage of the wound, which reduces the level of microbial contamination of the wound, reduces local swelling of tissues, activates local blood circulation, which promotes faster healing of wounds. The aim of the study. To improve the results of treatment of patients with gunshot wounds of soft tissues, using vacuum therapy and technomolecular silver preparations. Materials and methods. In 2022, there were 35 patients with gunshot wounds of soft tissues of various degrees of complexity undergoing inpatient treatment in the surgical and trauma departments of the Uzhhorod City Multidisciplinary Hospital. Patients were divided into two groups. The first group, the control group, included 18 patients who were treated with VAC therapy and water-based antiseptics in the complex treatment of wounds after dismantling the VAC therapy device. In the second, main group of patients, the complex of wound healing measures included VAC therapy and the use of technomolecular silver preparations in the form of a spray, which was applied to the wound once a day, after dismantling the VAC therapy device. Research results . The use of VAC-therapy accelerates the time of wound cleaning, and the use of technomolecular silver preparations promotes the active growth of granulations in significant wound defects, and active marginal epithelization on the surface where the granulations filled the defect. After dismantling the VAC-therapy device, the bacterial landscape of wounds decreased in almost all patients compared to the beginning of treatment. Also, preparations of technomolecular silver were applied for a long time to wounds in which autodermoplasty was performed, which contributed to good engraftment of transplanted skin flaps and faster healing of wounds. The duration of inpatient treatment of patients in the control group was 23.5±2.3 days, and in the main one – 19.4±2.1 days, which is 1.2 times faster than in the control group of patients. Conclusion. The use of the vacuum therapy method in the complex treatment of gunshot wounds, in combination with technomolecular silver preparations, helps to quickly clean the wound from necrotic tissues, activates the growth of granulations, and promotes good engraftment of transplanted skin flaps, which in general contributes to faster healing of wounds, and accordingly shortens the duration of an inpatient treatment.

Tumor Lysis Syndrome Following Thoracotomy Under Cardiopulmonary Bypass in a Case of Hepatocellular Carcinoma With Right Atrial and Inferior Vena Cava Tumor Thrombus

Tumor lysis syndrome (TLS) occurring after surgical resection of right atrium (RA) and inferior vena cava (IVC) tumor thrombus is a very rare but insidious condition. We report a case of hepatocellular carcinoma who developed TLS after uneventful excision of RA+IVC tumor thrombus under median sternotomy and cardiopulmonary bypass (CPB). Although the procedure was not expected to arouse massive tumor cell necrosis, post-operative course was complicated by metabolic acidosis, hypocalcemia, and progressive hyperkalemia indicative of TLS. Unfortunately, laboratory diagnosis of TLS was delayed under conditions of continuous renal replacement therapy (CRRT) for peri-operative acute renal failure. Despite all efforts, the patient died 36 hours after surgery due to lethal arrhythmia and disseminated infarction of the kidneys, spleen, and liver.

HMGB1-Induced Hepatocyte Pyroptosis Expanding Inflammatory Responses Contributes to the Pathogenesis of Acute-on-Chronic Liver Failure (ACLF).

BackgroundAcute-on-chronic liver failure (ACLF) is a critical disease with a high fatality rate. Immune dysfunction and inflammatory responses are key risk factors in ACLF. Pyroptosis is a form of programmed cell death characterized by the release of inflammatory cytokines, which causes the strong inflammatory responses. High mobility group box-1 (HMGB1) could induce pyroptosis and is closely related to ACLF. However, the role of HMGB1-induced hepatocyte pyroptosis in ACLF has never been proposed; whether HMGB1-induced hepatocyte pyroptosis participates in the development of ACLF and the mechanisms involved are barely understood.PurposeThis study aimed to clarify the roles of HMGB1-induced hepatocyte pyroptosis in ACLF and the molecular mechanisms involved.MethodsWistar rats were randomly divided into five groups, viz.: Normal, ACLF model, HMGB1 inhibitor, Caspase-1 inhibitor, and HMGB1 inhibitor+Caspase-1 inhibitor groups. The ACLF rat model was established using 40% carbon tetrachloride-induced liver fibrosis, followed by D-galactosamine and lipopolysaccharide joint acute attacks. The liver function, coagulation function and pathological damage of rats in each group were evaluated. The biological mechanisms of HMGB1-induced pyroptosis and the release of inflammatory cytokines were investigated using Western blot, quantitative real-time PCR (RT-qPCR), immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay.ResultsThe liver function and coagulation function of ACLF rats were seriously impaired; liver tissue showed massive or submassive necrosis, accompanied by inflammatory cell infiltration; the percentage of pyroptotic hepatocytes significantly increased, and a large number of inflammatory cytokines were released. The expression levels of pyroptosis-related genes and proteins in liver tissues and serum significantly increased. But these phenomenons were improved by the inhibition of HMGB1, and the dual inhibition of HMGB1 and Caspase-1 showed a stronger effect.ConclusionThe findings indicate, for the first time, that pyroptosis is a crucial pathophysiological event of ACLF involved in its pathogenesis, and HMGB1-induced hepatocyte pyroptosis expands inflammatory responses to aggravate ACLF, suggesting that it may be a potential therapeutic target for ACLF treatment.

Dramatic radiotherapy response of a giant T4 cutaneous squamous cell carcinoma of the scalp with extensive bone destruction: a case report

BackgroundPatients with large cutaneous squamous cell carcinoma of the scalp are a treatment challenge. We report a case of dramatic radiotherapy response of a patient with a giant cutaneous squamous cell carcinoma of the scalp with extensive skull destruction and suspected infiltration of the dura mater and superior sagittal sinus. This case is the first report of this kind in the literature that shows that large bone defects can heal with the resolution of tumor and inflammation by secondary intention without surgical reconstruction. We want to put an end to concerns about radiocurability of tumors with extensive bone involvement, and show sustained complete response after definitive radiotherapy and programmed cell death protein-1 inhibiting antibody therapy.Case presentationA 74-year-old White man presented with a 7.2 × 6.8 × 5.5 cm painless tumor on the right parietal region of the scalp. Medical imaging revealed widespread destruction of the skull and suspected infiltration of the dura mater and superior sagittal sinus. Biopsies showed cutaneous squamous cell carcinoma (cT4a cN0 cM0, stage IVA). The patient was treated with a total dose of 60 Gy, at 2 Gy per daily fraction with volumetric modulated arc therapy using 6 megavoltage photons. The biologically effective dose (alpha/beta 10 Gy) was 72 Gy. The tumor response correlated with dose received. The patient had a massive tumor necrosis secondary to tumor shrinkage after 18 fractions (36 Gy, biologically effective dose 43.2 Gy). Leakage of cerebrospinal fluid did not occur. Radiotherapy did not hamper the patient’s quality of life. The patient had a clear regression of the initial tumor on the final day of radiotherapy. The bone defect healed by secondary intention without surgical interventions. The patient achieved a complete response with a good cosmetic result after 82 days follow-up. He started a programmed cell death protein-1 inhibiting antibody therapy with cemiplimab 2 months after radiotherapy, and is now at 10 months follow-up without evidence of recurrence.ConclusionDefinitive radiotherapy is a safe and highly effective therapy for giant tumors of the scalp with extensive bone destruction. We report a sustained complete response with a good cosmetic result after secondary wound healing.

Photosensitization of a subcutaneous tumour by the natural anthraquinone parietin and blue light

Photodynamic therapy (PDT) is an anticancer treatment involving administration of a tumour-localizing photosensitizer, followed by activation by light of a suitable wavelength. In previous work, we showed that the natural anthraquinone (AQ) Parietin (PTN), was a promising photosensitizer for photodynamic therapy of leukemic cells in vitro. The present work aimed to analyze the photosensitizing ability of PTN in the mammary carcinoma LM2 cells in vitro and in vivo in a model of subcutaneously implanted tumours. Photodynamic therapy mediated by parietin (PTN-PDT) (PTN 30 µM, 1 h and 1.78 J/cm2 of blue light) impaired cell growth and migration of LM2 cells in vitro. PTN per se induced a significant decrease in cell migration, and it was even more marked after illumination (migration index was 0.65 for PTN and 0.30 for PTN-PDT, *p < 0.0001, ANOVA test followed by Tukey’s multiple comparisons test), suggesting that both PTN and PTN-PDT would be potential inhibitors of metastasis. Fluorescence microscopy observation indicated cytoplasmic localization of the AQ and no fluorescence at all was recorded in the nuclei. When PTN (1.96 mg) dissolved in dimethyl sulfoxide was topically applied on the skin of mice subcutaneously implanted with LM2 cells, PTN orange fluorescence was strongly noticed in the stratum corneum and also in the inner layers of the tumour up to approximately 5 mm. After illumination with 12.74 J/cm2 of blue light, one PDT dose at day 1, induced a significant tumour growth delay at day 3, which was not maintained in time. Therefore, we administered a second PTN-PDT boost on day 3. Under these conditions, the delay of tumour growth was 28% both on days 3 and 4 of the experiment (*p < 0.05 control vs. PTN-PDT, two-way ANOVA, followed by Sidak’s multiple comparisons test). Histology of tumours revealed massive tumour necrosis up to 4 mm of depth. Intriguingly, a superficial area of viable tumour in the 1 mm superficial area, and a quite conserved intact skin was evidenced. We hypothesize that this may be due to PTN aggregation in contact with the skin and tumour milieu of the most superficial tumour layers, thus avoiding its photochemical properties. On the other hand, normal skin treated with PTN-PDT exhibited slight histological changes. These preliminary findings encourage further studies of natural AQs administered in different vehicles, for topical treatment of cutaneous malignancies.

Histopathological changes in kidney and pancreas induced by energy drinks in adult male rats

The study aims to assess the impact of various doses of red bull on kidney and pancreas of male albino rats. Thirty male albino rats were assigned to three groups (10 animals/ group). Control group (1) received standard diet and water, group 2 and group 3 received daily oral doses of 10 ml/kg/rat and 20 ml/kg/rat of the energy drink (red bull) respectively for 30 days. Under light microscope no tissue changes were seen in kidney and pancreas of control group. In group 2 red bull causes vacuolar degeneration as well as coagulative necrosis of renal tubular epithelium, vascular congestion in the glomeruli and in the interstitial space of the kidney, in addition to atrophy of the glomeruli, as regard to pancreas it causes vascular congestion of the islets of Langerhans, increase in the size of the islets, besides, necrosis of Langerhans cells. In group 3 red bull leads to more atrophic glomeruli, massive coagulative necrosis of renal tubular epithelium, marked vascular dilatation and congestion in the interstitial space and degenerative changes of the renal tubular epithelium, whereas the pancreatic tissue revealed reduction in the size of the islets of Langerhans, vacuolation and degeneration of their cells, necrosis of other islets with mononuclear inflammatory cells infiltration and degenerative changes of pancreatic acini. It is concluded that administration of red bull to rats for 30 days will affect the histological structure of kidney as well as pancreas and this effect is a dose dependent.

Persistent Pneumonia in an Infant

An eight month old boy presented with a subacute febrile illness and radiological evidence of multifocal cavitatory consolidations in the lungs. He continued to worsen despite multiple oral and intravenous antibiotics. Preterminally, he developed respiratory distress, hepatosplenomegaly, bicytopenia, and hepatic dysfunction. Investigation for cause of persistent pneumonia resulted in a diagnosis of chronic granulomatous disease on the basis of Dihydrorhodamine assay and genetic analysis. Postmortem blood culture grew Burkholderia cenocepacia. Autopsy revealed necrotizing granulomatous inflammation with massive necrosis and abscesses in bilateral lungs. No organism could be identified by traditional stains on autopsy. Conventional PCR targeting 16S ribosomal DNA yielded Nocardia pseudobrasiliensis. In conclusion, an unusual course of pneumonia warrants invasive investigations for isolation of underlying organism, which not only provides guidance to choice of antimicrobials but also provides clue to an underlying disease.

Therapeutic potential of ginger against COVID-19: Is there enough evidence?

In addition to the respiratory system, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strikes other systems, including the digestive, circulatory, urogenital, and even the central nervous system, as its receptor angiotensin-converting enzyme 2 (ACE2) is expressed in various organs, such as lungs, intestine, heart, esophagus, kidneys, bladder, testis, liver, and brain. Different mechanisms, in particular, massive virus replication, extensive apoptosis and necrosis of the lung-related epithelial and endothelial cells, vascular leakage, hyper-inflammatory responses, overproduction of pro-inflammatory mediators, cytokine storm, oxidative stress, downregulation of ACE2, and impairment of the renin-angiotensin system contribute to the COVID-19 pathogenesis. Currently, COVID-19 is a global pandemic with no specific anti-viral treatment. The favorable capabilities of the ginger were indicated in patients suffering from osteoarthritis, neurodegenerative disorders, rheumatoid arthritis, type 2 diabetes, respiratory distress, liver diseases and primary dysmenorrheal. Ginger or its compounds exhibited strong anti-inflammatory and anti-oxidative influences in numerous animal models. This review provides evidence regarding the potential effects of ginger against SARS-CoV-2 infection and highlights its antiviral, anti-inflammatory, antioxidative, and immunomodulatory impacts in an attempt to consider this plant as an alternative therapeutic agent for COVID-19 treatment.

S2886 Exertional Heat Stroke-Induced Acute Liver Failure and Liver Transplantation: A Case Report

Introduction: Exertional heat stroke (EHS) is characterized by excessive heat production and inadequate heat dissipation usually following heavy exertion in hot and humid climates. This is a medical emergency associated with hyperthermia and multiorgan dysfunction, including acute liver failure (ALF). Currently, there are no clear guidelines regarding the timing of liver transplantation (LT) in this patient population. Case Description/Methods: A 44-year old marathon runner with no past medical history presented to an outside hospital after being found unconscious following a 5-mile run in summer weather. Vitals were 39.4°C, HR 103, and MAP 50s. He was intubated, fluid resuscitated, started on vasopressors and broad-spectrum antibiotics, and admitted to a local intensive care unit where he underwent external cooling. Labs were notable for acute liver and kidney injury and rhabdomyolysis (peak ALT 10,850 IU/L, AST 870 IU/L, Cr 5.6 mg/dL and CK 16K U/L), and he required renal replacement therapy (Figure 1). He then developed disseminated intravascular coagulopathy (peak INR 7.9), which persisted despite multiple transfusions. Hepatitis panel was negative. He received N-acetylcysteine. On day 3, he was transferred to our hospital for consideration of LT. He was alert and interactive even while intubated. He was extubated, but after 48 hours became progressively encephalopathic. Therefore, he was listed for transplant as Status 1 and underwent successful cadaveric LT on day 7. Liver explant showed massive hepatocyte necrosis (>80%) in zones 2 and 3 and portions of zone 1. The patient was discharged on day 32 with recovery of renal function and at baseline mental status. His hospitalization was complicated by the development of an intra-abdominal hematoma and deep venous thrombosis. Two years post-LT, he continues to exhibit good graft function. Discussion: The overall mortality in EHS-related liver injury or failure has been shown to be 4-5%, and the liver transplantation rate ranges from 12.5-33.3%, with median time to liver transplantation of 3 days. A high index of suspicion and careful monitoring of mental status and coagulopathy are warranted given the high mortality rate in this patient population. In this patient, the decision to perform liver transplant was made after the development of hepatic encephalopathy and continued coagulopathy despite maximal medical therapy. This case illustrates the importance of early liver transplantation referral in patients with EHS-induced ALF.Figure 1.: Trend of patient's AST, ALT and total bilirubin during hospitalization.

A-Lipoic Acid Alleviates Folic Acid-Induced Renal Damage Through Inhibition of Ferroptosis.

Folic acid (FA)-induced acute kidney injury (AKI) is characterized by the disturbance of redox homeostasis, resulting in massive tubular necrosis and inflammation. Α-lipoic acid (LA), as an antioxidant, has been reported to play an important role in renal protection, but the underlying mechanism remains poorly explored. The aim of this study is to investigate the protective effect of LA on FA-induced renal damage. Our findings showed that LA could ameliorate renal dysfunction and histopathologic damage induced by FA overdose injection. Moreover, FA injection induced severe inflammation, indicated by increased release of pro-inflammatory cytokines tumor necrosis factor (TNF)-α and IL-1β, as well as infiltration of macrophage, which can be alleviated by LA supplementation. In addition, LA not only reduced the cellular iron overload by upregulating the expressions of Ferritin and ferroportin (FPN), but also mitigated reactive oxygen species (ROS) accumulation and lipid peroxidation by increasing the levels of antioxidant glutathione (GSH) and glutathione peroxidase-4 (GPX4). More importantly, we found that LA supplementation could reduce the number of Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive tubular cells caused by FA, indicating that the tubular cell death mediated by ferroptosis may be inhibited. Further study demonstrated that LA supplementation could reverse the decreased expression of cystine/glutamate antiporter xCT (SLC7A11), which mediated GSH synthesis. What is more, mechanistic study indicated that p53 activation was involved in the inhibitory effect of SLC7A11 induced by FA administration, which could be suppressed by LA supplementation. Taken together, our findings indicated that LA played the protective effect on FA-induced renal damage mainly by inhibiting ferroptosis.

Histological Appearance Of The Liver In Experimental Injury

In this work, the morphofunctional state has been studied at various times after the simulation of experimental syphilis. It is noted that discirculatory and dystrophic changes develop in the early stages of the study. The appearance of focal and massive necrosis of hepatocytes is accompanied by the development of an inflammatory process in the form of lymphoid infiltration around necrosis and hypertrophy of Kupffer cells. Subsequently, lymphohistiocytic infiltration spreads along the portal tracts, in which plasma cells and eosinophils appear, which are characteristic of syphilitic inflammation.

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.

Higher circulating natural killer cells and lower lactate levels at admission predict spontaneous survival in non-acetaminophen induced acute liver failure

Massive cellular necrosis in acute liver failure (ALF) is dominantly immune mediated and innate immune cells are major pathophysiological determinants in liver damage.In fifty ALF and fifteen healthy, immune cells phenotyping by flow-cytometry, DAMPs using ELISA were analysed and correlated with clinical and biochemical parameters.ALF patients (aged 27 ± 9 yr, 56% males, 78% viral aetiology) showed no difference in neutrophils and classical monocytes, but significantly increased intermediate monocytes (CD14+CD16+) (p < 0.01), decreased non-classical monocytes (CD14−CD16+) and CD3-veCD16+CD56+ NK cells compared to HC. ALF patients who survived, showed higher NK cells (9.28 vs. 5.1%, p < 0.001) among lymphocytes and lower serum lactate levels (6.1 vs. 28, Odds ratio 2.23, CI 1.27–3.94) than non- survivors had higher. Logistic regression model predicted the combination of lactate levels with NK cell percentage at admission for survival.In conclusion, Combination of NK cell frequency among lymphocytes and lactate levels at admission can reliably predict survival of ALF patients.

Severe bowel complications in SARS-CoV-2 patients receiving protocolized care

Introduction and aimsA case series of ten patients that received protocolized care for SARS-CoV-2 infection and developed severe gastrointestinal complications, is presented. The aim of our study was to contribute to the ongoing discussion regarding gastrointestinal complications related to SARS-CoV-2 infection. After reviewing the current literature, ours appears to be the first detailed case series on the topic. Materials and methodsA retrospective filtered search of all patients admitted to our hospital for SARS-CoV-2 infection, who developed severe gastrointestinal complications, was performed. All relevant data on hospital patient management, before and after surgery, were collected from the medical records. ResultsOf the 905 patients admitted to our hospital due to SARS-CoV-2 infection, as of August 26, 2020, ten of them developed severe gastrointestinal complications. Seven of those patients were men. There were four cases of perforation of the proximal jejunum, three cases of perforations of the ascending colon, one case of concomitant perforation of the sigmoid colon and terminal ileum, one case of massive intestinal necrosis, and one preoperative death. Three right colectomies, four intestinal resections, one Hartmann’s procedure with bowel resection, and one primary repair of the small bowel were performed. The mortality rate of the patients analyzed was 50%. ConclusionSpontaneous bowel perforations and acute mesenteric ischemia are emerging as severe, life-threatening complications in hospitalized SARS-CoV-2 patients. More evidence is needed to identify risk factors, establish preventive measures, and analyze possible adverse effects of the current treatment protocols.