Zingiber officinale Root Capsule Extract Synergistically Enhance the Anti-Inflammatory Effects of Diclofenac Sodium in Experimental Acute Inflammation.

The present study aimed to evaluate the anti-inflammatory effects of ginger (Zingiber officinale) root capsule extract (GRCE) in doses of 100 mg/kg b.w. (body weight) and 200 mg/kg b.w. alone and in combination with a low dose (5 mg/kg b.w.) of diclofenac sodium (D) on carrageenan-induced acute inflammation (AI). The association of GRCE in a dose of 200 mg/kg b.w. with D offered the highest inhibition percentage for edema, reaching the maximum level of inhibition (95%) after 24 h. The association of GRCE in a dose of 200 mg/kg b.w. with D showed the ability to reduce tissue inflammatory changes when compared to D alone, while GRCE alone did not exhibit such properties. The association of both doses of GRCE with D showed significantly lower plasma and tissue levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) by up to 55% (p ≤ 0.0317), with the best results obtained by the group who received GRCE in the higher dose. These associations reduced the serum and tissue levels of prostaglandin-endoperoxide synthase 2 (COX-2) by up to 71% (p ≤ 0.0371). In conclusion, the association of GRCE with a low dose of D could be an appropriate combination to decrease the dose used to reduce serum and tissue levels of inflammatory molecules, edema, and histological changes in acute inflammation. Further research will be necessary to achieve clinical evaluation.

Flurona: The First Autopsied Case.

COVID-19-associated coinfections increase the patient's risk of developing a severe form of the disease and, consequently, the risk of death. The term "flurona" was proposed to describe the coinfection of the influenza virus and SARS-CoV-2. This report is about a case of a 7-month-old female infant who died due to flurona coinfection. A histopathological exam showed activation of microglia (becoming CD45 positive), bronchial inflammation, diffuse alveolar damage in proliferative phase with vasculitis, a peribronchial infiltrate that was predominantly CD20-positive, and a vascular wall infiltrate that was predominantly CD3-positive. The aggressiveness of the two respiratory viruses added up and they caused extensive lung inflammation, which led to respiratory failure, multiple organ failure, and death. Tissues injuries caused by both the influenza virus and SARS-CoV-2 could be observed, without the ability to certify the dominance of the aggression of one of the two viruses.

Anti-Inflammatory and Analgesic Effects of Curcumin Nanoparticles Associated with Diclofenac Sodium in Experimental Acute Inflammation.

The present study evaluated the anti-inflammatory and analgesic effects of conventional curcumin (cC) and curcumin nanoparticles (nC) associated with diclofenac sodium (D) in experimental acute inflammation (AI) induced by carrageenan administration. Seven groups of eight randomly selected Wistar-Bratislava white rats were evaluated. One group was the control (C), and AI was induced in the other six groups. The AI group was treated with saline solution, the AID group was treated with D, the AIcC200 and AInC200 groups were treated with cC and nC, respectively, while AIcC200D and AInC200D were treated with cC and nC, respectively, both associated with D. Conventional curcumin, nC, and D were administered in a single dose of 200 mg/kg b.w. for cC and nC and 5 mg/kg b.w. for D. Association of cC or nC to D resulted in significant antinociceptive activity, and improved mechanical pressure stimulation and heat thresholds at 3, 5, 7 and 24 h (p < 0.03). The association of cC and nC with D (AIcC200D and AInC200D groups) showed significantly lower plasma and tissue levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) up to 2.5 times, with the best results in the group who received nC. Moreover, AInC200D presented the least severe histopathological changes with a reduced level of inflammation in the dermis and hypodermis. The combination of nC to D showed efficiency in reducing pain, inflammatory cytokines, and histological changes in acute inflammation.

Fatal Form of COVID-19 in a Young Male Bodybuilder Anabolic Steroid Using: The First Autopsied Case.

We report the case of a 34-year-old male patient, a bodybuilding trainer and user of anabolic androgenic steroids (AASs) for 16 years. He was found in cardio-respiratory arrest in his home. By performing a medico-legal autopsy, a severe form of COVID-19, aortic atherosclerotic plaques, and an old myocardial infarction was found. The SARS-CoV-2 RT-PCR test on necroptic lung fragments was positive, with a B.1.258 genetic line. The histopathological examinations showed microthrombi with endothelitis in the cerebral tissue, massive pulmonary edema, diffuse alveolar damage grade 1, pulmonary thromboembolism, hepatic peliosis, and severe nesidioblastosis. The immunohistochemical examinations showed SARS-CoV-2 positive in the myocardium, lung, kidneys, and pancreas. ACE-2 receptor was positive in the same organs, but also in the spleen and liver. HLA alleles A*03, A*25, B*18, B*35, C*04, C*12, DRB1*04, DRB1*15, DQB1*03, DQB1*06 were also identified. In conclusion, death was due to a genetic predisposition, a long-term abuse of AASs that favored the development of a pluriorganic pathological tissue terrain, and recent consumption of AASs, which influenced the immune system at the time of infection.

COVID-19 and Pneumocystis jirovecii Pulmonary Coinfection-The First Case Confirmed through Autopsy.

Background: Establishing the diagnosis of COVID-19 and Pneumocystisjirovecii pulmonary coinfection is difficult due to clinical and radiological similarities that exist between the two disorders. For the moment, fungal coinfections are underestimated in COVID-19 patients. Case presentation: We report the case of a 52-year-old male patient, who presented to the emergency department for severe dyspnea and died 17 h later. The RT-PCR test performed at his admission was negative for SARS-CoV-2. Retesting of lung fragments collected during autopsy revealed a positive result for SARS-CoV-2. Histopathological examination showed preexisting lesions, due to comorbidities, as well as recent lesions: massive lung thromboses, alveolar exudate rich in foam cells, suprapleural and intra-alveolar Pneumocystisjirovecii cystic forms, and bilateral adrenal hemorrhage. Conclusion: COVID-19 and P.jirovecii coinfection should be considered, particularly in critically ill patients, and we recommend the systematic search for P. jirovecii in respiratory samples.

Age-Related Changes of the Pineal Gland in Humans: A Digital Anatomo-Histological Morphometric Study on Autopsy Cases with Comparison to Predigital-Era Studies.

Background and objectives: The pineal gland is a photoneuroendocrine organ in the midline of the brain, responsible primarily for melatonin synthesis. It is composed mainly of pinealocytes and glial tissue. This study examined human postmortem pineal glands to microscopically assess age-related changes using digital techniques, and offers a perspective on evolutionary tendencies compared to the past. Materials and Methods: A retrospective autopsy study has been performed on 72 pediatric and adult autopsy cases. The glands have been processed for histological analysis and immunohistochemical staining with glial fibrillary acidic protein (GFAP). Slides were assessed under polarized light and digitally scanned. Morphometric data were obtained using CaseViewer and ImageJ. Results: Thirty-three females and 39 males were included in the study, grouped under three age groups: 0-25, 46-65, and 66-96 years of age. The peak gland volume was found within the 46-65 age group, the overall mean volume was 519 mm3, the main architectural types were lobular and insular, and the mean percentage of pineal calcification was 15% of the gland, peaking within the 66-96 age group, with a predominantly globular shape. Glial cysts were found in 20.8% of cases. The intensity of GFAP stain was maximal in the pediatric age group, but the extent of glial tissue was much larger in elderly patients. Discussion: The degenerative process of the pineal gland can be quantified by measuring normal parenchyma, calcifications, glial tissue, and glial cysts. Morphometric differences have been observed and compared to a similar studies performed in the published literature. The current study, unfortunately, lacks a 26-45 age group. Digital techniques seemed to offer a more exact analysis, but returned similar results to studies performed over 40 years ago, therefore offering important information on evolutionary tendencies. Conclusions: Increase in glial tissue, calcifications, and glial cysts have a defining role as age-related changes in the pineal gland.

Tibolone, alendronate, and simvastatin enhance implant osseointegration in a preclinical in vivo model.

OBJECTIVES: The objective of the study was to evaluate and compare the effect of different drugs such as simvastatin, alendronate, and tibolone for titanium implant osseointegration enhancement. MATERIALS AND METHODS: Eighty female albino Wistar rats were equally divided into five groups: Group I (ovariectomy), Group II (sham ovariectomy), Group III (alendronate + ovariectomy), Group IV (simvastatin + ovariectomy), and Group V (tibolone + ovariectomy). Three months after ovariectomy, we performed bilateral titanium intramedullary nailing in all groups, followed by oral administration of alendronate, simvastatin, or tibolone for 12 weeks. Examinations included micro-CT, mechanical pull-out test, histology, and bone serum markers. RESULTS: Peri-implant micro-CT analysis showed a significantly higher overall bone tissue in tibolone compared to the ovariectomy group, while no significant difference was found between the treatment groups. Sham ovariectomy, alendronate, and tibolone groups had a higher body mass density compared to ovariectomy and simvastatin groups. All treatment groups had a greater thickness of the peri-implant compact bone layer compared to ovariectomy group, but the results were not statistically significant. Tibolone presented the highest values in pull-out test, but alendronate showed more consistently positive results compared to other groups. Osteocalcin had in the tibolone group almost three times the value in the ovariectomy group, but the results were not statistically significant. CONCLUSION: The hypothesis that alendronate, simvastatin, and tibolone enhance the osseointegration process of intramedullary titanium implants in ovariectomized rats has been accepted, while tibolone could offer the best results.

Biological and Histological Assessment of the Hepatoportoenterostomy Role in Biliary Atresia as a Stand-Alone Procedure or as a Bridge toward Liver Transplantation.

Background and objectives: In patients with biliary atresia (BA), hepatoportoenterostomy (HPE) is still a valuable therapeutic tool for prolonged survival or a safer transition to liver transplantation. The main focus today is towards efficient screening programs, a faster diagnostic, and prompt treatment. However, the limited information on BA pathophysiology makes valuable any experience in disease management. This study aimed to analyze the evolution and survival of patients with BA referred for HPE (Kasai operation) in our department. Materials and Methods: A retrospective analysis was performed on fourteen patients with BA, diagnosed in the pediatric department and further referred for HPE in our surgical department between 2010 and 2016. After HPE, the need for transplantation was assessed according to patients cytomegalovirus (CMV) status, and histological and biochemical analysis. Follow-up results at 1-4 years and long term survival were assessed. Results: Mean age at surgery was 70 days. Surgery in patients younger than 60 days was correlated with survival. Jaundice's clearance rate at three months was 36%. Total and direct bilirubin values had a significant variation between patients with liver transplants and native liver (p = 0.02). CMV was positive in eight patients, half with transplant need and half with native liver survival. Smooth muscle actin (SMA) positivity was proof of advanced fibrosis. The overall survival rate was 79%, with 75% for native liver patients and an 83% survival rate for those with liver transplantation. Transplantation was performed in six patients (43%), with a mean of 10 months between HPE and transplantation. Transplanted patients had better survival. Complications were diagnosed in 63% of patients. The mean follow-up period was six years. Conclusions: HPE, even performed in advanced cirrhosis, allows a significant survival, and ensures an essential time gain for patients requiring liver transplantation. A younger age at surgery is correlated with a better outcome, despite early CMV infection.

Curcumin Nanoparticles Protect against Isoproterenol Induced Myocardial Infarction by Alleviating Myocardial Tissue Oxidative Stress, Electrocardiogram, and Biological Changes.

Curcumin from Curcuma longa is a nutraceutical compound reported to possess strong antioxidant activity that makes it a candidate for use in counteracting oxidative stress-induced damage. The effect of pre-treatment with curcumin nanoparticles (nC) compared to conventional curcumin (Cs) on blood pressure, electrocardiogram, and biological changes on isoproterenol (ISO)-induced myocardial infarction (MI) in rats had been investigated. The Cs doses of 150 and 200 mg/kg bw and all nC doses (100, 150 and 200 mg/kg bw) significantly reduced heart rate before ISO administration and prevented QRS complex enlargement after MI induction (p < 0.026). All doses of Cs and nC prevented prolongation of the QT and QT corrected (QTc) intervals, with better results for higher doses (p < 0.048). The nC solution had more significant results than Cs in all metabolic parameters assessed (lactate dehydrogenase, glycaemia, aspartate transaminase, and alanine transaminase, p < 0.009). nC was more efficient than Cs in limiting myocardial oxidative stress and enhancing antioxidative capacity (p < 0.004). Compared to Cs, nC better prevented myocardial damage extension, reduced interstitial oedema, and inflammation. Curcumin nanoparticles as compared to conventional curcumin exert better antioxidative effects. Moreover, nC better prevent cardiomyocytes damage, and electrocardiogram alterations, in the case of ISO-induced MI in rats.

Intestinal Infarction Through Arterial Vascular Obstruction - Case Series from 1st and 3rd Surgery Clinics Cluj-Napoca.

This article presents a case series of intestinal infarction through obstruction of superior mesenteric artery - two cases of acute mesenteric artery embolism, two cases of acute mesenteric artery thrombosis and a case of volvulus.

Dental follicle stem cells in bone regeneration on titanium implants.

BACKGROUND: We aimed to demonstrate that DF stem cells from impacted molars and canines can be used to improve bone regeneration on titanium implants surfaces. This study highlights the presence of stem cells in DF, their potential to adhere and differentiate into osteoblasts on different types of titanium surfaces. RESULTS: Isolated cells from the harvested DF tissue from impacted canine/molars, expressed stem cells markers. Differentiation into bone cells was induced in presence or absence of BMP-2 and TGFß1. The presence of growth factors until 28 days in medium maintained the cells in an earlier stage of differentiation with a lower level of specific bone proteins and a higher expression of alkaline phosphatase (ALP). Influence of titanium implants with different bioactive coatings, hydroxyapatite (TiHA) and with silicatitanate (TiSiO2), and porous Ti6Al7Nb implants as control (TiCtrl), was studied in terms of cell adhesion and viability. Ti HA implants proved to be more favorable for adhesion and proliferation of DF stem cells in first days of cultivation. The influence of titanium coatings and osteogenic differentiation mediums with or without growth factors were evaluated. Additional BMP-2 in the medium did not allow DF stem cells to develop a more mature phenotype, leaving them in a pre-osteogenic stage. The best sustained mineralization process evaluated by immuno-cytochemical staining, scanning electron microscopy and Ca(2+) quantification was observed for TiHA implants with a higher expression of ALP, collagen and Ca(2+) deposition. Long term culturing (70 days) on titanium surfaces of DF stem cells in standard medium without soluble osteogenic inducers, indicated that HA coating is more favorable, with the acquisition of a more mature osteoblastic phenotype as shown by immunocytochemical staining. These findings demonstrated that even in absence of exogenous osteogenic factors, TiHA implants and in a lesser extent TiCtrl and TiSiO2 implants can induce and sustain osteogenic differentiation of DF stem cells, by their chemical and topographical properties. CONCLUSIONS: Our research demonstrated that DF stem cells have a spontaneous tendency for osteogenic differentiation and can be used for improving bone regeneration on titanium implants surfaces.

Sudden death from ruptured choroid plexus arteriovenous malformation.

Brain vascular malformations are recognized as having potential to produce hemorrhage, but leading to sudden death in children is uncommon. Arteriovenous malformations may be situated in any region of the brain, but very rarely, they can be restricted to the choroid plexus. We report here a rare case of sudden death in a child, caused by a ruptured vascular malformation with an unusual location, which was not identified grossly but only on histological examination. The size and the location of the lesion, as well as the age of our patient, were contributing factors of the massive bleeding. Autopsy remains an important tool because it provides valuable information about the etiology of such bleedings, improves knowledge about these lesions, and enhances epidemiologic data.

Histological Changes in the Popliteal Artery Wall in Patients with Critical Limb Ischemia.

INTRODUCTION: This prospective study aims to illustrate the histopathological arterial changes in the popliteal artery in peripheral arterial disease of the lower limbs. MATERIAL AND METHOD: A total of 60 popliteal artery segments taken from patients who had undergone lower limb amputation were examined between April and June 2023. The degree of arterial stenosis, medial calcinosis, and the vasa vasorum changes in the arterial adventitia were quantified. The presence of risk factors for atherosclerosis was also observed. RESULTS: Atherosclerotic plaque was found in all of the examined segments. Medial calcinosis was observed in 40 (66.6%) of the arterial segments. A positive association between the degree of arterial stenosis and the vasa vasorum changes in the arterial adventitia was also found (p = 0.025). The level of blood sugar and cholesterol were predictive factors for the severity of atherosclerosis. CONCLUSIONS: Atherosclerosis and medial calcinosis are significant in patients who underwent lower limb amputation. Medial calcinosis causes damage to the arterial wall and leads to a reduction in responsiveness to dilator stimuli.

Digital histological morphometry of the human pineal gland in a postmortem study, with endocrine and neurological clinical implications.

The pineal gland is a small-sized, photo neuroendocrine organ in the midline of the brain that synthesises and secretes melatonin and serotonin. Chords and islands of pinealocytes constitute the secretory parenchyma, while glial tissue and calcifications represent degenerative changes. This study examined human postmortem pineal glands to microscopically assess morphological changes possibly associated with clinical data, by using digital techniques. A retrospective autopsy study has been performed on 72 paediatric and adult autopsy cases. The glands have been processed for histological analysis and immunohistochemical staining with synaptophysin (SYN), neuron-specific enolase (NSE), and neurofilament (NF). Slides were digitally scanned. Morphometric data were obtained using CaseViewer and ImageJ. The comorbidities used for correlation with morphometric data were obesity, type 2 diabetes, adrenal gland adenoma, goitre, chronic pancreatitis, arterial hypertension, and mixed dementia. Thirty-three females and 39 males were included in the study. Increased secretory parenchyma was found in patients with chronic pancreatitis, arterial hypertension, and adrenal gland adenoma. Reduced activity was found in patients with type 2 diabetes, obesity, advanced pineal calcification, mixed dementia, and old age. There were no changes associated with goitre, cachexia, or Willis's polygon atherosclerosis. No significant differences between gender were found. The activity of the pineal gland can be assessed by quantitative immunohistochemistry of neuroendocrine and structural pinealocyte markers and observation of glial tissue and calcifications. There is a need for further research to evaluate the clinical impact of these morphological changes on the neuroendocrine systems, with clinical implications in endocrinology, neurology, and even psychiatry. Digital techniques offer a more exact analysis of histological data.

Effects of Gold Nanoparticles Phytoreduced with Rutin in an Early Rat Model of Diabetic Retinopathy and Cataracts.

Diabetic retinopathy (DR) and cataracts (CA) have an early onset in diabetes mellitus (DM) due to the redox imbalance and inflammation triggered by hyperglycaemia. Plant-based therapies are characterised by low tissue bioavailability. The study aimed to investigate the effect of gold nanoparticles phytoreduced with Rutin (AuNPsR), as a possible solution. Insulin, Rutin, and AuNPsR were administered to an early, six-week rat model of DR and CA. Oxidative stress (MDA, CAT, SOD) was assessed in serum and eye homogenates, and inflammatory cytokines (IL-1 beta, IL-6, TNF alpha) were quantified in ocular tissues. Eye fundus of retinal arterioles, transmission electron microscopy (TEM) of lenses, and histopathology of retinas were also performed. DM was linked to constricted retinal arterioles, reduced endogen antioxidants, and eye inflammation. Histologically, retinal wall thickness decreased. TEM showed increased lens opacity and fibre disorganisation. Rutin improved retinal arteriolar diameter, while reducing oxidative stress and inflammation. Retinas were moderately oedematous. Lens structure was preserved on TEM. Insulin restored retinal arteriolar diameter, while increasing MDA, and amplifying TEM lens opacity. The best outcomes were obtained for AuNPsR, as it improved fundus appearance of retinal arterioles, decreased MDA and increased antioxidant capacity. Retinal edema and disorganisation in lens fibres were still present.

Ginger (Zingiber officinale) Root Capsules Enhance Analgesic and Antioxidant Efficacy of Diclofenac Sodium in Experimental Acute Inflammation.

Our study aimed to evaluate the analgesic and antioxidant effects of ginger (Zingiber officinale) root capsule extract (GRCE) in addition to diclofenac (D) sodium treatment in carrageenan-induced acute inflammation (AI). Seven groups of eight Wistar-Bratislava white rats were included in the study. One group was the control (C), and AI was induced in the other six groups. The following treatments were applied: saline solution for C and AI groups, D for the AID group, GRCE for two groups and GRCE and D for another two groups. The GRCE was administered by gavage in two doses (100 mg/Kg b.w. or 200 mg/kg b.w.), while D was administered intraperitoneally in a dose of 5 mg/kg b.w. The association of GRCE with this low dose of diclofenac reduced pain threshold and improved mobility with the best results for the dose of 200 mg/kg b.w. Moreover, this combination reduced, better than D alone, the serum levels of the evaluated pro-oxidant parameters (malondialdehyde, the indirect assessment of NO synthesis, total oxidative status and oxidative stress index) up to 78%, especially oxidative stress index (p < 0.0001). GRCE alone slightly improved the antioxidant parameters (total antioxidant capacity and total thiols), but when associated with, D the results were better, especially for total thiols as their plasma levels increased up to 50% (p < 0.0010), with the best results obtained for the 200 mg/kg b.w. dose of GRCE. In conclusion, ginger root capsules associated with diclofenac might offer additional antioxidant and analgesic effects in a dose-dependent manner in acute inflammation.

Histopathological Lung Findings in COVID-19 B.1.617.2 SARS-CoV-2 Delta Variant.

BACKGROUND: The Delta variant (Pango lineage B.1.617.2) is one of the most significant and aggressive variants of SARS-CoV-2. To the best of our knowledge, this is the first paper specifically studying pulmonary morphopathology in COVID-19 caused by the B.1.617.2 Delta variant. METHODS: The study included 10 deceased patients (40-83 years) with the COVID-19 Delta variant. The necrotic lung fragments were obtained either by biopsy (six cases) or autopsy (four cases). Tissue samples were subjected to virology analysis for identification of the SARS-CoV-2 variant, histopathology, and immunohistochemistry (anti-SARS coronavirus mouse anti-virus antibody). RESULTS: Virology analysis identified B.1.617.2 through genetic sequencing in eight cases, and in two cases, specific mutations of B.1.617.2 were identified. Macroscopically, in all autopsied cases, the lung had a particular appearance, purple in color, with increased consistency on palpation and abolished crepitations. Histopathologically, the most frequently observed lesions were acute pulmonary edema (70%) and diffuse alveolar damage at different stages. The immunohistochemical examination was positive for proteins of SARS-CoV-2 in 60% of cases on alveolocytes and in endothelial cells. CONCLUSIONS: The histopathological lung findings in the B.1.617.2 Delta variant are similar to those previously described in COVID-19. Spike protein-binding antibodies were identified immunohistochemically both on alveolocytes and in the endothelial cells, showing the potential of indirect damage from thrombosis.

Techniques for digital histological morphometry of the pineal gland.

INTRODUCTION: The pineal gland is a small photo-neuro-endocrine organ. This study used human post-mortem pineal glands to microscopically assess immunohistochemical marker intensity and percentage of positivity using known and novel digital techniques. MATERIALS AND METHODS: An experimental non-inferiority study has been performed on 72 pineal glands harvested from post-mortem examinations. The glands have been stained with glial fibrillary acidic protein (GFAP), synaptophysin (SYN), neuron-specific enolase (NSE), and neurofilament (NF). Slides were digitally scanned. Morphometric data were obtained using optical analysis, CaseViewer, ImageJ, and MorphoRGB RESULTS: Strong and statistically significant correlations were found and plotted using Bland-Altman diagrams between the two image analysis software in the case of mean percentage and intensity of GFAP, NSE, NF, and SYN. DISCUSSIONS: Software such as SlideViewer and ImageJ, with our novel software MorphoRGB were used to perform histological morphometry of the pineal gland. Digital morphometry of a small organ such as the pineal gland is easy to do by using whole slide imaging (WSI) and digital image analysis software, with potential use in clinical settings. MorphoRGB provides slightly more accurate data than ImageJ and is more user-friendly regarding measurements of parenchyma percentage stained by immunohistochemistry. The results show that MorphoRGB is not inferior in functionality. CONCLUSIONS: The described morphometric techniques have potential value in current practice, experimental small animal models and human pineal glands, or other small endocrine organs that can be fully included in a whole slide image. The software we used has applications in quantifying immunohistochemical stains.

Neurotoxicity of Bisphenol A and the Impact of Melatonin Administration on Oxidative Stress, ERK/NF-kB Signaling Pathway, and Behavior in Rats.

Bisphenol A (BPA) exposure can be associated with neurodevelopmental disorders due to impairment of cell proliferation and synaptic development. Our study evaluated the effects of melatonin (MEL) on ambulatory activity, lipid peroxidation, cytokines, ERK/NF-kB signaling pathway in the hippocampus and frontal lobe, and histopathological changes in the hippocampus of the BPA-treated rats. The animals were divided into 4 groups: control, BPA, BPA + MEL I, and BPA + MEL II. MEL I (20 mg/kg b.w.) and MEL II (40 mg/kg b.w.) were orally administered for 28 days. On the 29th day, BPA (1 mg/kg b.w.) was intraperitoneally administered, and, after 24 h, an open field test (OFT) and an elevated plus maze (EPM) were conducted. The results showed that the MEL II group made significantly more entries in the open arms of EPM, traveled significantly greater distance, and spent more time in the central part of OFT. Malondialdehyde levels were diminished by MEL II in the hippocampus and by MEL I in the frontal lobe. In the hippocampus, the MAPK level was significantly lowered by both doses of MEL (p < 0.05) while in the frontal lobe, only MEL II reduced the MAPK activation. MEL I and II significantly decreased the γH2AX and upregulated the NFkB and pNFkB expressions in the hippocampus while MEL II downregulated the MCP1 expression. Both doses of MEL attenuated the BPA-evoked histopathological alterations in the hippocampus. These data indicate that MEL can mediate the neuroprotection against BPA-induced neurotoxicity and improves behavioral changes suggesting a real potential as a protective agent in brain toxicity.

The Evaluation of the Four-Chamber Cardiac Dissection Method of the Fetal Heart as an Alternative to Conventional Inflow-Outflow Dissection in Small Gestational-Age Fetuses.

The examination of very small fetal hearts requires special equipment and a specialist that are not available in many general pathology laboratories. Compared to conventional examination, the four-chamber cardiac dissection (4CCD) method can be performed by any pathologist using instruments generally available in pathology services. The aim of this study is to evaluate the efficiency of the 4CCD method in the examination of small fetal hearts using post-mortem magnetic resonance imaging (pm-MRI) at 7T as the standard. Twelve fetuses with gestational ages between 13 and 19 weeks have been included in this study. All fetuses underwent pm-MRI examination prior to pathologic examination. The 4CCD method was used for the cardiac examination in all cases following the same guidelines for cardiac sectioning. The 4CCD was able to identify all cardiac anatomic structures as compared to pm-MRI at 7T, demonstrating a sensibility of 95.8% (95% CI, 94.5-95.8) and specificity of 100% (95% CI, 32.3-100). The overall accuracy in identifying cardiac anatomic structures was 95.8% (95% CI, 93.4-95.8). Additionally, the 4CCD method was able to detect cardiac anomalies with an overall diagnostic accuracy of 91% (95% CI, 85.8-94.2), sensibility of 67.6% (95% CI, 54.5-75.3), and specificity of 97% (95% CI, 93.7-99) as compared to pm-MRI at 7T. The four-chamber view dissection method can be considered as an alternative to the conventional inflow-outflow dissection method in selected cases.