Intracellular Edema Research Articles

Effects of Diet-Induced Obesity and Programs for Body Weight Reduction on the Histostructure of the Triceps Surae Muscle in Male Rats.

We studied the effects of visceral obesity induced by a high-calorie diet and health-improving variants of its correction on morphological characteristics of the muscle tissue in male Wistar rats. At stage I, the rats received standard (StD) or high-calorie diet (HCD) for 8 weeks. At stage II, the animals were divided into the following subgroups: no correction (StD and HCD), switching from HCD to StD (HCD/StD) and/or connection of physical activity in the form of treadmill running (StD+running, HCD+running, and HCD/StD+running) for the next 8 weeks. Diet-induced visceral obesity was shown to result in a decrease in the weight of the triceps surae muscle, fatty infiltration, intracellular edema, partial lysis of contractile elements, weak inflammatory response, and decreased muscle fiber area on cross section. Treadmill running (HCD+running) exacerbates the morphological changes, but returns muscle fiber area to normal. Correction of visceral obesity and relative normalization of muscle tissue structure was noted when switching to a standard diet (HCD/StD and HCD/StD+running).

Мікрорівнева адаптація окремих органів і тканин стерляді (Acipenser ruthenus Linnaeus, 1758) в умовах теплового стресу

Purpose. To evaluate the variability of the histological parameters of individual organs and tissues of sterlet, to establish the level of effect of heat stress on the physiological status of fish and the degree of their adaptation. To determine the perspective of using histological monitoring data in fish farming practice. Methodology. The primary materials were obtained in aquarium conditions of the Aquatic Bioresources Laboratory of the Kherson State Agrarian and Economic University. The laboratory processing of histological samples was performed according to generally accepted methods and manuals. Histological studies were carried out using the author’s equipment and original methods, specially intended for the diagnostics of fish tissues. The obtained results were processed by methods of variational statistics using a package of appropriate MS Excel applications, with emphasis on the standard error. Findings. Microanatomical studies of sterlet showed that under conditions of heat stress, the most significant changes occur in adipose tissue, somatic and cardiac muscle tissue, thyroid gland and renal tissue, which can conditionally be considered as bioindicative zones. Under the potential influence of the thermal factor, the response of sterlet is expressed in a decrease in the lipid content in the accompanying muscles of adipose tissue. The effect is visualized in the fragmentation and subsequent shredding of lipid vacuoles, which leads to variability in adipocyte shape from stellate to spindle-shaped. The obtained results indicate a decrease in the excretion of thyroid hormones into the bloodstream by the thyroid gland and is expressed in a gradual increase in the diameter of the thyroid follicles (by 16.0 µm and 26.5 µm) and a corresponding decrease in the height of the follicular cells (by 1.1 µm and 2.0 µm), which is statistically significant. Intensive development of “additional” follicles inside existing ones indicates the prevention of thyroid intoxication of the body, which indicates the development of an adaptive reaction of the body. Comparative studies of the ventricular myocardium of fish allowed establishing certain morphological differences in the form of moderate interstitial edema of the tissue and intracellular edema of cardiomyocytes. In the final phase of the experiment, karyopyknosis was locally observed in the ventricular cardiomyocytes of 50% of stressed fish. Somatic muscle tissue is generally resistant to stress, but the rate of its development at elevated temperatures slows down. Characteristic signs of the histological picture of muscle stress are approximately the same ratio of stromal and parenchymal components, the central orientation of the nuclei within a single muscle fiber and insufficient filling of the fibers with the fibrillar component. Antidiuretic hormone is forcedly released in fish under conditions of heat stress, which leads to a decrease in the volume of the primary filtrate. Evidence is a narrow gap in the urinary space between the visceral and parietal layers of the renal corpuscle. Originality. New data are presented and existing data on the histological structure of individual organs and tissues of sterlet under stress loads are significantly expanded. For the first time, a detailed histological analysis of the structure of muscle, adipose tissue, as well as the kidney and thyroid gland of sterlet under heat stress conditions was carried out. The comparative analysis, current and updated information on compensatory changes in tissues demonstrate their adaptive potential, which was developed during the evolution of the species. Practical Value. The information obtained is of value in morphophysiological studies as well as in fish farming practice in connection with the modern problem of a decrease in the life status of fish under stress. The use of the obtained data allows a qualitative assessment of the physiological state and can be used in the process of developing corrective measures in order to consolidate hereditary resistance, which is ultimately aimed at preventing diseases of valuable aquaculture objects. Keywords: sterlet, heat stress, adaptation, muscle tissue, thyroid gland, myocardium, adipose tissue, renal tissue.

White Sponge Nevus of the oral mucosa – Case report

White sponge nevus (WSN) is a rare autosomal-dominant disorder of the non-keratinized mucosa, characterized by a thickened white edematous mucosa whose surface appears irregular, wrinkly, or spongy. It affects mainly the oral mucosa. The histopathological examination demonstrates hyperparakeratosis, acanthosis with intracellular edema and vacuolization over the prickle cell layer, and eosinophilic perinuclear condensation. The currently accepted etiology is a mutation of the keratin 4 and/or keratin 13 genes. We present a case of WSN diagnosed in a 30-year-old white male patient with white corrugated bilateral lesions on the buccal mucosa that extended beyond the occlusal plane. A biopsy was obtained, and the histological presentation included superficial parakeratosis, prominent acanthosis of the squamous epithelium, and areas with prominent intracellular edema, which confirmed the diagnosis. No treatment was necessary other than patient counseling and initial 6-month follow-up consultation. His attending dentist was informed of the diagnosis, and further follow-ups were recommended.

Pathomorphological characteristics of heat stress in the experiment.

The purpose of this research was to explore some morphological, physiological, and biochemical changes in female and fetal Wistar rats under heat stress. The experiment involved 30 animals, including two experimental groups (pregnant and nonpregnant females) kept under heat stress at 32°C and one control group consisting of healthy individuals kept in standard vivarium conditions. After dissection, fixation, dehydration, and primary processing, tissue samples were embedded in a mixture of paraffin and lanolin to obtain material for sections. Sections were made using a freezing and angular microtome and stained with hematoxylin and fuchsine solutions. Changes in morphology were assessed by microscopy using a Leitz DIAPLAN system. As a result of heat stress, an increase in linear cell size, capillary network area, and adrenal mass was observed; adipocytes lost lipid vacuoles; prismatic thyroid cells were replaced by flat cells; hypothyroidism; an increase in the number of osteocyte lacunae; and increased osteoclast activity in bone tissue; interstitial and intracellular oedema and caryopycnosis of ventricular cardiomyocytes; reduction in the diameter of skeletal muscle fibers and replacement of tissue with collagen fibers; water loss in the structure of myofibrils; destructive local changes, hyperchromatosis and caryopycnosis of the hippocampus. The data obtained allows predicting the possible consequences of prolonged overheating of tissues of other vertebrates and the human body.

Enhancement of Vitamin C's Protective Effect against Thimerosal-Induced Neurotoxicity in the Cerebral Cortex of Wistar Albino Rats: An In Vivo and Computational Study.

Vitamin C was examined to ameliorate the neurotoxicity of thimerosal (THIM) in an animal model (Wistar albino rats). In our work, oxidative and antioxidative biomarkers such as SOD, LPO, and GSH were investigated at various doses of THIM with or without concurrent vitamin C administration. Furthermore, the adverse effects of THIM on hepatic tissue and cerebral cortex morphology were examined in the absence or presence of associated vitamin C administration. Also, we studied the effect of vitamin C on the metallothionein isoforms (MT-1, MT-2, and MT-3) in silico and in vivo using the RT-PCR assay. The results showed that the antioxidant biomarker was reduced as the THIM dose was raised and vice versa. THIM-associated vitamin C reduced the adverse effects of the THIM dose. The computation studies demonstrated that vitamin C has a lower ΔG of -4.9 kcal/mol compared to -4.1 kcal/mol for THIM to bind to the MT-2 protein, which demonstrated that vitamin C has a greater ability to bind with MT-2 than THIM. This is due to multiple hydrogen bonds that exist between vitamin C and MT-2 residues Lys31, Gln23, Cys24, and Cys29, and the sodium ion represents key stabilizing interactions. Hydrogen bonds involve electrostatic interactions between hydrogen atom donors (e.g., hydroxyl groups) and acceptors (e.g., carbonyl oxygens). The distances between heavy atoms are typically 2.5-3.5 Å. H-bonds provide directed, high-affinity interactions to anchor the ligand to the binding site. The five H-bonds formed by vitamin C allow it to form a stable complex with MT, while THIM can form two H-bonds with Gln23 and Cys24. This provides less stabilization in the binding pocket, contributing to the lower affinity compared to vitamin C. The histopathological morphologies in hepatic tissue displayed an expansion in the portal tract and the hepatocytes surrounding the portal tract, including apoptosis, binucleation, and karyomegaly. The histopathological morphologies in the brain tissue revealed a significant decrease in the number of Purkinje cells due to THIM toxicity. Interestingly, THIM toxicity was associated with hemorrhage and astrogliosis. Both intracellular and vasogenic edema appeared as the concentrations of THIM rose. Finally, vitamin C ameliorated the adverse effect on the cerebral cortex in Wistar albino rats.

Potential Anti-Toxoplasmosis Efficiency of Phoenix dactylifera Extracts Loaded on Selenium Nanoparticles.

Toxoplasmosis is a parasitic disease caused by Toxoplasma gondii that infects humans and many types of mammals and birds. To investigate the effect of selenium nanoparticles (SeNPs) and Phoenix dactylifera (Pd) extracts loaded on SeNPs as a new agent to combat chronic T. gondii infections in murine model as an alternative method to standard Spiramycin drug therapy. A total of 64 female mice were randomly divided into eight groups: GI: Normal control, GII: Positive control, GIII: infected and treated with Spiramycin, GIV: infected and treated with SeNPs, GV: infected and treated with aqueous extract of Pd, GVI: infected and treated with methanolic extract of Pd, GVII: infected and treated with aqueous extract of Pd loaded on SeNPs, GVIII: infected and treated with methanolic extract of Pd loaded on SeNPs. Date palm (P. dactylifera) fruits were identified and collected from the farms of Saudi Arabia. Preparation and characterization of SeNPs were done. The parasitological, histopathological examinations and biochemical changes were evaluated in all groups. Parasitological results showed significant differences in GVII in comparison to GII while GVIII showed significant differences in comparison to GII and GIII. The histopathological section of the cerebral cortex showed obvious alterations in the infected compared with untreated control groups. Aqueous and methanolic extracts of P. dactylifera loaded on SeNPs treatment showed improvement that indicated by few perivascular cuffing with few inflammatory cell infiltrations. Few granule cells with mild intracellular vacuolation and edema few deformed neurons with deep pyknotic nuclei. Microglia cells expression of Iba-1 and inflammatory cytokines (IL-4, IL-10 and INF-γ) in serum of all groups was higher in GII and lowest in GVIII followed by GVII. SeNPs and P. dactylifera extracts loaded on SeNPs could be a potent agent to combat T. gondii infections.

MORPHOLOGICAL CHANGES OF RATS’ CEREBRAL CORTEX UNDER CONDITIONS OF DMH-INDUCED EXPERIMENTAL CARCINOGENESIS

Abstract. The progression of the endogenous intoxication syndrome accompanies the development of any neoplasm. The infl uence of toxic products leads to signifi cant disruptions in homeostasis, which seriously aff ects the central nervous system, specifi cally the cortex of the large hemispheres. Therefore, the purpose of our study was to establish changes in the morphological reorganization of the cortex of the large hemispheres of rats with DMG-induced adenocarcinoma in situ. The study used 85 mature white male rats. All animals were divided into 2 groups: I – 35 intact animals and II – 50 animals with DMG-induced colon adenocarcinoma.Histological slides of the brain were prepared by the generally accepted methodology. The drugs were studied using a MICROmed SEO SCAN light microscope and photo- documented using a Vision CCD Camera. The histological organization of the cerebral cortex of intact animals had typical histoarchitectonics. In the fi rst three stages of the experiment, moderate changes in the morphological organization of the cortex were detected compared to the control group. The fourth stage of DMG-induced carcinogenesis modeling was characterized by the manifestation of morphological changes, a decrease in the number of normochromic, an increase in hypo- and hyperchromic neurocytes, and the appearance of cell alteration signs. Typical for this period also was the progression of hemodynamic disorders: venous hyperemia, stasis, aggregation of erythrocytes («sludge»), and an increase in perivascular and pericellular edema. At the 5th and 6th stages of the experiment, a violation of the cytoarchitectonics of the cortex was revealed. Destructive changes in neurocytes increased. Betz cells were in a state of tigrolysis, sometimes in total one. A decrease in the Nissl substance in neurons confi rmed their impaired functional capacity. Increased permeability of capillary walls led to severe pericellular edema of neurocytes. Intracellular edema was also detected in most neurocytes. The 7th stage of the induced carcinogenesis was characterized by the presence of severe destructive changes in neurons: an increase in the number of hypo-, hyperchromic, sharply hypo-, and sharply hyperchromic neurocytes, a fragmentation of neurocyte neuroplasm, most of Betz cells in a state of total tigrolysis, a decrease in the content of Nissl substance in them, up to its complete absence. Blood capillaries had a deformed wall and signifi cantly enlarged perivascular spaces. Consequently, the study established the development and dynamics of alterative changes in the neurocytes of the cerebral cortex caused by DMG-induced carcinogenesis. These disorders were characterized by alteration of neurocytes and progressive microcirculation disorders. All identifi ed morphological changes in the brains of aff ected animals prove their dependence on the duration of carcinogen exposure.

Single Cerebral Metastasis Mimicking Pyogenic Abscess in a Patient with Lung Adenocarcinoma.

HomeRadiology: Imaging CancerVol. 5, No. 3 Images in CancerFree AccessSingle Cerebral Metastasis Mimicking Pyogenic Abscess in a Patient with Lung AdenocarcinomaVíctor Pérez-Riverola , Olalla Vázquez Muiños, Mario Prenafeta Moreno, Roser Monmany Badia, Khalid El-Hamshari Rebollo, Esther Granell MorenoVíctor Pérez-Riverola , Olalla Vázquez Muiños, Mario Prenafeta Moreno, Roser Monmany Badia, Khalid El-Hamshari Rebollo, Esther Granell MorenoAuthor AffiliationsFrom the Department of Neuroradiology, UDIAT-CD, Hospital Universitari Parc Taulí, Parc del Taulí 1, 08208 Sabadell, Spain.Address correspondence to V.P.R. (email: [email protected]).Víctor Pérez-Riverola Olalla Vázquez MuiñosMario Prenafeta MorenoRoser Monmany BadiaKhalid El-Hamshari RebolloEsther Granell MorenoPublished Online:Apr 7 2023https://doi.org/10.1148/rycan.230004MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In As clinical signs of infection are often absent in patients with pyogenic abscesses, differential diagnosis with cerebral metastases is based on MRI findings.However, both entities often manifest as ring-enhancing lesions. Pyogenic brain abscesses usually show restricted diffusion in the lesion core and the dual-rim sign at susceptibility-weighted imaging. The dual-rim sign consists of two concentric rims bordering the lesion: a complete, smooth outer hypointense rim representing the fibrocollagenous capsular wall and an inner hyperintense rim representing a zone of granulation tissue (1). At perfusion imaging, the capsule of a cerebral abscess has a lower relative cerebral blood volume than the necrotic or cystic peripheral wall of a tumor due to microvessel angiogenesis by the tumor (2).Some cerebral metastases also show restricted diffusion, which does not correlate with the histologic type of the primary cancer (3). Proposed mechanisms for restricted diffusion in metastases include intracellular edema in viable tumor cells during transition to complete liquefactive necrosis (4) and a highly viscous mucin concentration (5).Key findings that help distinguish these atypical metastases from pyogenic abscess include high peripheral wall relative cerebral blood volume and absence of the dual-rim sign (Figure).Brain MR images in a 37-year-old male patient, a heavy tobacco and cannabis smoker, after a first seizure. (A) Contrast-enhanced T1-weighted MR image shows a smooth, ring-enhancing nodular right frontal lobe lesion surrounded by abundant vasogenic edema. (B, C) On diffusion-weighted images, the central core shows restricted diffusion. (D) On susceptibility-weighted image, a hypointense smooth ring completely surrounds the lesion, simulating a capsule. (E) The relative cerebral blood volume of the lesion’s peripheral wall (arrows) is high (mean relative cerebral blood volume ratio: 7.61 ± 2.70 [SD]). Chest CT findings (not shown) detected a cavitary pulmonary mass. Tests for tuberculosis and bronchoalveolar lavage fluid analysis were negative. Chest CT findings were initially misinterpreted as an infectious process. Follow-up brain MRI 8 weeks after starting antibiotics showed enlargement of the frontal lobe lesion, new ring-enhancing cerebral and cerebellar lesions, and signs of leptomeningeal carcinomatosis in the posterior fossa. The patient was diagnosed with lung adenocarcinoma following lung lesion biopsy.Download as PowerPointOpen in Image Viewer Disclosures of conflicts of interest: V.P.R. No relevant relationships. O.V.M. No relevant relationships. M.P.M. No relevant relationships. R.M.B. No relevant relationships. K.E.H.R. No relevant relationships. E.G.M. No relevant relationships.Keywords: MRI, MR-Diffusion-weighted Imaging, MR-Perfusion, Metastasis, Neuro-oncology, Lung Adenocarcinoma, Pyogenic AbscessAuthors declared no funding for this work.

Travmatik Beyin Hasarı Sıçan Modelinde Sesamol’ün İkincil Yaralanmaya Karşı Koruyucu Etkileri

Objective: Sesamol is a powerful antioxidant, anti-inflammatory, antiapoptotic, and neuroprotective chemical. This study aimed to investigate the histopathological effects of sesamol in a rat traumatic brain injury (TBI) model. Material and Methods: Thirty-two male rats were divided into the following four groups: control, trauma, vehicle, and sesamol. All groups were subjected to TBI, and immediately after trauma saline and sesamol (100 mg/kg) were administered intraperitoneally to the vehicle and sesamol groups, respectively. At 24th hour of TBI, brain samples were collected, and histomorphological investigation of brain parenchyma was performed using electron and light microscopy. Results:On histopathological investigation, TBI induced brain injury was lesser than trauma and vehicle groups in the sesamol group. Compared to the trauma group, in the sesamol group there was less perivascular region edema. The neuronal processes of the sesamol group also displayed less intracellular edema and vacuoles. Conclusion:The results of the current study revealed for the first time that sesamol exhibits neuroprotective effects against TBI.

Copper sulfate induces clinico-hematological, oxidative stress, serum biochemical and histopathological changes in freshwater fish rohu (Labeo rohita).

Despite being an essential trace element for numerous metabolic processes and micronutrients, copper (Cu) has induced adverse effects on the environment and public health due to its continuous and widespread use for the last several decades. The current study assessed the hematological and histopathological alterations in the freshwater fish (Labeo rohita) exposed to graded concentrations of copper sulfate. For this purpose, L. rohita fish (n = 72), weighing ~200-215 g, were randomly divided into four experimental groups and then exposed to acute doses of CuSO4, i.e., control, 0.28, 0.42, and 0.56 μgL-1. For comparative analysis of hematological and biochemical changes, blood/serum samples were obtained on 12, 24, and 36 days. Overall, the body weight of fish decreased with the time and dose of CuSO4; as the dose increases, body weight decreases. Dose and time-dependent results were observed in other parameters also. Results showed a significant increase in leukocytes, whereas red blood cells count, Hb, and Hct were significantly reduced in treated groups compared to the control. The mean corpuscular hemoglobin (MHC) and mean corpuscular hemoglobin concentration (MCHC) showed a non-significant decrease in treated groups compared to the control group. Serum biochemical parameters, including total proteins, albumin, and globulin, decreased significantly (p < 0.05). At the same time, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), glucose, and cholesterol were significantly (p < 0.05) increased in the treated groups compared to the control group. Significantly (p < 0.05) increased levels of lipid peroxidation while decreased values of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (RGSH) in the blood of fish were recorded. Histopathological examination of fish gills, liver, and kidneys showed inflammation and degenerative changes due to CuSO4 exposure. In the brain tissue, degenerative changes like neuron necrosis, intracellular edema, cytoplasmic vacuolization, and congestion were observed. In conclusion, the study indicates that exposure to copper sulfate, even in smaller concentrations, can cause adverse hematological and histopathological changes in L. rohita fish.

English

Pesticides especially insecticides are widely used in the field of agricultural development all over the world to increase crop production. Moreover, exposure to such compounds does not only influence the intended targets but also induces adverse impacts on a number of unintended targets in animals. This research aimed to determine the toxic impacts of lufenuron (an insecticide) on the health status of fish in terms of measurement of oxidative stress, antioxidant enzymes, DNA damage and histopathological changes in Nile tilapia (Oreochromis niloticus) exposed to different concentrations. For this purpose, Oreochromis niloticus fish, weighing about 75-80g were arbitrarily separated into four different groups and then exposed to lufenuron @ 0.7, 1.2 and 1.7µg/ L for 39 days. The results showed that the fish exposed to the pesticide had significant changes in oxidative stress, antioxidant profile in gills and percentile rate of DNA damage in different visceral organs including liver, kidney, and gills. Results of light microscopic investigations indicated different histological changes in liver (necrosis of hepatocytes, degeneration of hepatocytes, vacuolar degeneration and congestion), gills (necrosis of lamellar epithelial cells, telangiectasia, and atrophy of secondary lamellae), heart (congestion, necrosis of neurons, microgliosis and intracellular edema), brain (congestion, myofibrosis, neutrophilic and myocarditis) and kidneys (necrosis of renal tubules, widening of urinary space, necrosis of renal tubular epithelial cells). A significantly escalate in oxidative stress while lower quantity of antioxidant biomarkers was documented in experimental fish. The findings of this study suggest that long-term exposure to lufenuron has negative health effects via induction of DNA damage, increased oxidative stress, lowering of enzymatic antioxidants profile and histological lesions in visceral organs of Nile tilapita (Oreochromis niloticus).

Eozinofilni ezofagitis

Eosinophilic esophagitis (EoE) is an inflammatory disorder characterized by intraepithelial eosinophilic infiltration followed by esophageal dysfunction. Pathophysiological mechanism of EoE is still not well understood, with several factors that may contribute, such as host immunity, environmental and genetic factors. Modern diagnostic for EoE should include: esophageal dysfunction, esophageal biopsy with at least 15 eosinophils per high power field and absence of other pathology characterized by increased number of eosinophils. The most common presenting symptoms in adults are dysphagia, heartburn, food impaction and chest pain. Children are usually presented with nausea and vomiting, anorexia, heartburn, regurgitation, chest burn and abdominal pain. Endoscopically, patients with EoE are characterized by longitudinal furrows (vertical lines, darker than surrounding mucosa), esophageal trachealization (numerous transversal rings, as in trachea), exudate (white plaques), edema (decreased mucosal vascularization), strictures and crepe-paper mucosa (mucosal friability and tearing during endoscopy). Histological features of EoE could be separated into major and minor criteria. Major criteria include: intraepithelial infiltration by eosinophils (&gt;15 eosinophils/HPF), eosinophilic microabscesses (≥4 eosinophils in a collection), eosinophils occupying outer layer of the squamous epithelium, epithelial sloughing and eosinophil degranulation. Minor criteria include: basal zone hyperplasia, lengthening of the epithelial papillae, intracellular edema and subepithelial fibrosis. In order to set adequate diagnosis, all other conditions related to increased number of eosinophils should be excluded. The most common and the most important differential is gastroesophageal reflux disease (GERD). Treatment of the EoE encompasses: proton pump inhibitors (PPI), corticosteroids (topical and systemic), elimination diet and esophageal dilation.

Morphological characteristics and notes of the skin in preclinical toxicity assessment.

In this review, the histological structures of the skin are summarized for fundamental knowledge for toxicological assessment. The skin is composed of epidermis, dermis, subcutaneous tissue, and associated adnexa. In the epidermis, keratinocytes comprise four layers, and three other cell types, besides keratinocytes, play various roles. Epidermal thickness varies with species and body site. In addition, it can be affected by tissue preparation procedures, which can render toxicity assessments difficult. Bulge stem cells are the origin of sebaceous glands, epidermal basal layer, and hair follicle formation, and they play an important role in the maintenance of the basic structure of the skin. Stem cells and appendages formed from stem cells sometimes become toxic targets, and it is useful to study the origins of the hair follicle/hair cycle to interpret their toxicity. Irritant contact dermatitis and allergic contact dermatitis are the main adverse reactions in topical application studies. The mechanism involves direct chemical irritation of the skin, and histologically, epidermal necrosis and accompanying inflammatory cell infiltration. In allergic contact dermatitis, an inflammatory reaction and intercellular or intracellular edema, histologically represented by lymphocytic infiltration of the epidermis and dermis, are observed. Regional and species differences exist in the dermal absorption of compounds, and differences in the thickness of the stratum corneum substantially contribute to these differences. Learning the basic structures, functions, and possible artifacts will contribute to the evaluation of skin toxicity by topical and systemic applications.

Aquaporin 11 alleviates retinal Müller intracellular edema through water efflux in diabetic retinopathy

Retinal Müller glial dysfunction and intracellular edema are important mechanisms leading to diabetic macular edema (DME). Aquaporin 11 (AQP11) is primarily expressed in Müller glia with unclear functions. This study aims to explore the role of AQP11 in the pathogenesis of intracellular edema of Müller glia in diabetic retinopathy (DR). Here, we found that AQP11 expression, primarily located at the endfeet of Müller glia, was down-regulated with diabetes progression, accompanied by intracellular edema, which was alleviated by intravitreal injection of lentivirus-mediated AQP11 overexpression. Similarly, intracellular edema of hypoxia-treated rat Müller cell line (rMC-1) was aggravated by AQP11 inhibition, while attenuated by AQP11 overexpression, accompanied by enhanced function in glutamate metabolism and reduced cell death. The down-regulation of AQP11 was also verified in the Müller glia from the epiretinal membranes (ERMs) of proliferative DR (PDR) patients. Mechanistically, down-regulation of AQP11 in DR was mediated by the HIF-1α-dependent and independent miRNA-AQP11 axis. Overall, we deciphered the AQP11 down-regulation, mediated by miRNA-AQP11 axis, resulted in Müller drainage dysfunction and subsequent intracellular edema in DR, which was partially reversed by AQP11 overexpression. Our findings propose a novel mechanism for the pathogenesis of DME, thus targeting AQP11 regulation provides a new therapeutic strategy for DME.

The compatibility between optical coherence tomography and fundus fluorescein angiography in the detection of macular edema involving the fovea

Objective: To investigate the compatibility between optical coherence tomography (OCT) and fundus fluorescein angiography (FFA) in the detection of macular edema (ME) excluding subretinal fluid (SRF) involving the fovea. Materials and methods: In this retrospective study in the Ophthalmology Department at our university hospital, interpretation of OCT and FFA images was performed for 200 eyes that underwent simultaneous FFA and OCT to rule out ME. The cases having SRF were excluded from the study. Results: Of 200 eyes, 193 eyes (96.5%) had the finding of ME confirmed by both techniques. There were 2 eyes (1%) for which FFA revealed ME involving fovea with hyperfluorescence in the macula while OCT demonstrated no intraretinal edema or subretinal fluid in the macula. For 5 eyes in the study (2.5%), OCT revealed intraretinal edema in the fovea, while these were not detected by FFA. Conclusion: This study suggests that FFA and OCT are highly sensitive techniques for the detection of ME and they correlate with each other. The little discrepancy between OCT and FFA for determining ME may be due to intracellular or extracellular edema and fast or slower development of retinal edema.

Electronic-microscopic changes of the heart of old rats with hyperhomocystemia

Annotation. Hyperhomocysteinemia (HHCys) is a pathological condition characterized by an increase in plasma homocysteine (HCys) levels above 15 μmol/l and causes abnormal functioning of the human body. Increasing the concentration of HCys in plasma can cause structural and functional changes in all organs and systems of the body, but, as research shows, the most vulnerable is the cardiovascular system. The aim of the research is to study the ultrastructural changes in the heart of old rats under conditions of HHCys. The experimental study was performed on 22 white nonlinear old (24-26 months) male rats. During the experiment, the animals were divided into two groups – control and experimental. Simulation of persistent HHCys was achieved by administering to rats the experimental group thiolactone HCys at a dose of 200 mg/kg body weight intragastrally for 60 days. Ultrathin sections were studied in the PEM – 125K electron microscope. It was found that the introduction of thiolactone HCys to old rats at a dose of 200 mg/kg is associated with the development of destructive-dystrophic changes in the heart of animals. They are visible in all layers of the organ in the form of a significant increase in the volume of connective tissue. The lumens of most hemocapillaries were dilated and filled with blood cells. In endotheliocytes there are severe ultrastructural disorders, manifested by the disappearance of micropinocytic vesicles and caveolae, the formation of large caveolae-like structures, which led to a violation of transcapillary metabolism. Intracellular edema, hypertrophied mitochondria with locally enlightened matrix, destroyed crystals, damaged outer membrane were found in cardiomyocytes. Myofibrils became thinner, they showed lysis of myofibrils.

Cortical thickness and hippocampal volume in adolescent children with obstructive sleep apnea.

Intermittent hypoxia and sleep fragmentation due to obstructive sleep apnea (OSA) may contribute to oxidative tissue damage and apoptotic neuronal cell death, inflammation, and intracellular edema in the brain. We examined whether OSA in overweight and obese adolescent children is associated with cortical thickness and hippocampal structure compared to overweight and obese controls and whether OSA severity is associated with measures of brain integrity. We calculated cortical thickness and hippocampal subfield volumes from T1-weighted images of 45 controls (age 15.43 ± 1.73 years, 21 male) and 53 adolescent children with OSA (age 15.26 ± 1.63 years, 32 male) to investigate the association of childhood OSA with the alteration of cortical structure and hippocampal subfield structural changes. In addition, we investigated the correlation between OSA severity and cortical thickness or hippocampal subfield volume using Pearson's correlation analysis. We found cortical thinning in the right superior parietal area of adolescent children with OSA (cluster size 32.29 mm2, cluster-wise corrected p-value = .030) that was negatively correlated with apnea-hypopnea index (AHI) (R=-0.27, p-value = .009) and arousal index (R=-0.25, p-value = .014). In addition, the volume of the right subiculum-head area of the hippocampus of adolescent children with OSA was larger than controls (0.19 ± 0.02 ml vs. 0.18 ± 0.02 ml, β = 13.79, false discovery rate corrected p-value = .044), and it was positively correlated with AHI (R = 0.23, p-value = .026) and arousal index (R = 0.31, p-value = .002). Our findings provide evidence for OSA-associated brain structure alterations in adolescent children prior to the onset of treatment that likely have important implications for timely intervention and continued monitoring of health outcomes.

Shock lung is not “wet” but characterized as necroptotic inflammation in a mouse model of hypotension

ObjectivesHypotension episodes before or after donor brain death are assumed to trigger hypoxia-reoxygenation, causing diffuse alveolar-capillary damage via necrosis. However, alveolar-capillary membranes have direct access to oxygen in alveoli. We hypothesized hypotension-induced lung injury is not diffuse alveolar-capillary damage but interstitial inflammation resulting from nonhypoxic lung ischemia and systemic responses to hypoxic extrapulmonary ischemia. MethodsThe 4-hour hypotension model was established by subjecting C57BL/6J mice to 4-hour hypotension at 15 ± 5 mm Hg of mean artery pressure and resuscitated with whole shed blood and norepinephrine. Nonhypoxic lung ischemia model was established by 4-hour left pulmonary artery ligation. At 24 hours postprocedure, an arterial blood gas analysis and a gastroduodenal occult blood test were conducted. Lung samples were assessed for histology, cytokine transcripts, regulated cell death, and alveolar-capillary permeability. ResultsThe 4-hour hypotension model had an intraoperative mortality rate of 17.7% (41/231) and a stress-ulcer bleeding rate of 15.3% (29/190). No signs of alveolar flooding were observed in both models. Four-hour hypotension without stress ulcer showed normal oxygenation and permeability but increased interstitial infiltration, transcription of Tnf and Il1b, phosphorylation of MLKL and RIPK3, and cleaved caspase 3 compared with 4-hour pulmonary artery ligation and naïve control. Animals that developed stress ulcer presented with worse pulmonary infiltration, intracellular edema, and oxygenation but just slightly increased permeability. Immunoblotting showed significant upregulations of protein expression and phosphorylation of MLKL and RIPK3, cleaved Caspase-3, but not its prototype in 4-hour hypotension with stress ulcer. ConclusionsHypotensive lung injury is essentially a nonhypoxic ischemia–reperfusion injury enhanced by systemic responses. It is predominated by necroptosis-induced inflammation rather than necrosis-induced diffuse alveolar-capillary damage.

Defining Wound Healing Progression in Cetacean Skin: Characteristics of Full-Thickness Wound Healing in Fraser's Dolphins (Lagenodelphis hosei).

Simple SummaryCutaneous wound healing is a complex and tightly regulated biological process to restore physiological and anatomic function. Current knowledge of cutaneous wound healing is mostly based on studies in laboratory animals and humans. The histological and immunological features of skin, for example, cutaneous thickness, cellular components, and immune response, are not identical among animal species, and these differences may lead to substantial effects in cutaneous wound healing. In field observation, large cutaneous wounds in cetaceans could heal without medical treatments. However, little is known about the underlying mechanisms, and there is no histological study on full-thickness wound healing in cetaceans. The current study characterizes the macroscopic and histological features of large full-thickness wound healing in Fraser’s dolphins (Lagenodelphis hosei). The differences of wound healing between cetaceans and terrestrial mammals were shown from the histological aspect, including rete and dermal ridge appearance, repigmentation, and adipose tissue regeneration. Better understanding of the mechanism of full-thickness wound healing in cetaceans will shed light on veterinary and human regenerative medicine, leading to novel therapies.Cetaceans are tight-skinned mammals that exhibit an extraordinary capacity to heal deep soft tissue injuries. However, essential information of large full-thickness wound healing in cetaceans is still lacking. Here, the stages of full-thickness wound healing were characterized in Fraser’s dolphins (Lagenodelphis hosei). The skin samples were collected from normal skin and full-thickness cookiecutter shark (Isistius brasiliensis)-bite wounds of stranded carcasses. We defined five stages of wound healing according to macroscopic and histopathological examinations. Wounds in Stage 1 and 2 were characterized by intercellular and intracellular edema in the epidermal cells near the wound edge, mixed inflammatory cell infiltration, and degradation of collagen fibers. In Stage 3 wounds, melanocytes, melanin granules, rete and dermal ridges were noticed in the neo-epidermis, and the adipose tissue in adjacent blubber was replaced by cells and fibers. Wounds in Stage 4 and 5 were characterized by gradual restoration of the normal skin architecture including rete and dermal ridges, collagen bundles, and adipose tissue. These phenomena were quite different from previous studies in terrestrial tight-skinned mammals, and therefore, further in-depth research into the mechanisms of dolphin wound healing would be needed to gain new insights into veterinary and human regenerative medicine.

Local glucose metabolism is unaltered in reversible splenial lesion syndrome.

Transient splenial oedema, also known as reversible splenial lesion syndrome (RESLES), is a rare magnetic resonance imaging (MRI) finding that presents as a round or ovoid focal oedema in the posterior corpus callosum, and is associated with a wide range of clinical conditions. The aetiology of RESLES is not fully clear. We aimed to investigate conflicting pathophysiological hypotheses by measuring local glucose metabolism in patients with RESLES. We retrospectively analysed patients with RESLES after reductions in antiseizure medications during in-hospital video electroencephalography monitoring. We measured local glucose uptake using positron emission tomography/computed tomography and compared matched cohorts of patients with and without MRI evidence of RESLES using nonparametric tests. Local glucose metabolism in the splenium of seven patients with RESLES was not significantly different from the glucose metabolism of the seven patients in the matched cohort. This was true using both regular and normalized standardized glucose uptake value calculation methods (p=0.902 and p=0.535, respectively). We found no evidence of local glucose hypometabolism in RESLES, which supports previous pathophysiological considerations that suggest that RESLES is an intercellular, intramyelinic oedema rather than a typical intracellular cytotoxic oedema, which is not reversible.