International Journal Of Experimental Pathology[JOURNAL]
Sun
200 papers
Screening of plants from the Brazilian Atlantic Forest led to the identification of Athenaea velutina (Solanaceae) as a novel source of antimetastatic agents.
Almeida AA, Lima GDA, Simão MVRC … +7 more , Moreira GA, Siqueira RP, Zanatta AC, Vilegas W, Machado-Neves M, Bressan GC, Leite JPV
Int J Exp Pathol · 2020 Jun · PMID 32452573 · Full text
Plant biodiversity is a source of potential natural products for the treatment of many diseases. One of the ways of discovering new drugs is through the cytotoxic screening of extract libraries. The present study evaluat...
Plant biodiversity is a source of potential natural products for the treatment of many diseases. One of the ways of discovering new drugs is through the cytotoxic screening of extract libraries. The present study evaluated 196 extracts prepared by maceration of Brazilian Atlantic Forest trees with organic solvents and distilled water for cytotoxic and antimetastatic activity. The MTT assay was used to screen the extract activity in MCF-7, HepG2 and B16F10 cancer cells. The highest cytotoxic extract had antimetastatic activity, as determined in in vitro assays and melanoma murine model. The organic extract of the leaves of Athenaea velutina (EAv) significantly inhibited migration, adhesion, invasion and cell colony formation in B16F10 cells. The phenolic compounds and flavonoids in EAv were identified for the first time, using flow injection with electrospray negative ionization-ion trap tandem mass spectrometry analysis (FIA-ESI-IT-MS ). EAv markedly suppressed the development of pulmonary melanomas following the intravenous injection of melanoma cells to C57BL/6 mice. Stereological analysis of the spleen cross-sections showed enlargement of the red pulp area after EAv treatment, which indicated the activation of the haematopoietic system. The treatment of melanoma-bearing mice with EAv did not result in liver damage. In conclusion, these findings suggest that A velutina is a source of natural products with potent antimetastatic activity.
A PIK3CA transgenic mouse model with chemical carcinogen exposure mimics human oral tongue tumorigenesis.
Tan MT, Wu JG, Callejas-Valera JL … +4 more , Schwarz RA, Gillenwater AM, Richards-Kortum RR, Vigneswaran N
Int J Exp Pathol · 2020 Feb · PMID 32436348 · Full text
Oral cancer causes significant global mortality and has a five-year survival rate of around 64%. Poor prognosis results from late-stage diagnosis, highlighting an important need to develop better approaches to detect ora...
Oral cancer causes significant global mortality and has a five-year survival rate of around 64%. Poor prognosis results from late-stage diagnosis, highlighting an important need to develop better approaches to detect oral premalignant lesions (OPLs) and identify which OPLs are at highest risk of progression to oral squamous cell carcinoma (OSCC). An appropriate animal model that reflects the genetic, histologic, immunologic, molecular and gross visual features of human OSCC would aid in the development and evaluation of early detection and risk assessment strategies. Here, we present an experimental PIK3CA + 4NQO transgenic mouse model of oral carcinogenesis that combines the PIK3CA oncogene mutation with oral exposure to the chemical carcinogen 4NQO, an alternate experimental transgenic mouse model with PIK3CA as well as E6 and E7 mutations, and an existing wild-type mouse model based on oral exposure to 4NQO alone. We compare changes in dorsal and ventral tongue gross visual appearance, histologic features and molecular biomarker expression over a time course of carcinogenesis. Both transgenic models exhibit cytological and architectural features of dysplasia that mimic human disease and exhibit slightly increased staining for Ki-67, a cell proliferation marker. The PIK3CA + 4NQO model additionally exhibits consistent lymphocytic infiltration, presents with prominent dorsal and ventral tongue tumours, and develops cancer quickly relative to the other models. Thus, the PIK3CA + 4NQO model recapitulates the multistep genetic model of human oral carcinogenesis and host immune response in carcinogen-induced tongue cancer, making it a useful resource for future OSCC studies.
Experimental models and methods for cutaneous wound healing assessment.
Masson-Meyers DS, Andrade TAM, Caetano GF … +4 more , Guimaraes FR, Leite MN, Leite SN, Frade MAC
Int J Exp Pathol · 2020 Feb · PMID 32227524 · Full text
Wound healing studies are intricate, mainly because of the multifaceted nature of the wound environment and the complexity of the healing process, which integrates a variety of cells and repair phases, including inflamma...
Wound healing studies are intricate, mainly because of the multifaceted nature of the wound environment and the complexity of the healing process, which integrates a variety of cells and repair phases, including inflammation, proliferation, reepithelialization and remodelling. There are a variety of possible preclinical models, such as in mice, rabbits and pigs, which can be used to mimic acute or impaired for example, diabetic and nutrition-related wounds. These can be induced by many different techniques, with excision or incision being the most common. After determining a suitable model for a study, investigators need to select appropriate and reproducible methods that will allow the monitoring of the wound progression over time. The assessment can be performed by non-invasive protocols such as wound tracing, photographic documentation (including image analysis), biophysical techniques and/or by invasive protocols that will require wound biopsies. In this article, we provide an overview of some of the most often needed and used: (a) preclinical/animal models including incisional, excisional, burn and impaired wounds; (b) methods to evaluate the healing progression such as wound healing rate, wound analysis by image, biophysical assessment, histopathological, immunological and biochemical assays. The aim is to help researchers during the design and execution of their wound healing studies.
ADAMTS-5: A difficult teenager turning 20.
Santamaria S
Int J Exp Pathol · 2020 Feb · PMID 32219922 · Full text
A Disintegrin And Metalloproteinase with ThromboSpondin motif (ADAMTS)-5 was identified in 1999 as one of the enzymes responsible for cleaving aggrecan, the major proteoglycan in articular cartilage. Studies in vitro, ex...
A Disintegrin And Metalloproteinase with ThromboSpondin motif (ADAMTS)-5 was identified in 1999 as one of the enzymes responsible for cleaving aggrecan, the major proteoglycan in articular cartilage. Studies in vitro, ex vivo and in vivo have validated ADAMTS-5 as a target in osteoarthritis (OA), a disease characterized by extensive degradation of aggrecan. For this reason, it attracted the interest of many research groups aiming to develop a therapeutic treatment for OA patients. However, ADAMTS-5 proteoglycanase activity is not only involved in the dysregulated aggrecan proteolysis, which occurs in OA, but also in the physiological turnover of other related proteoglycans. In particular, versican, a major ADAMTS-5 substrate, plays an important structural role in heart and blood vessels and its proteolytic processing by ADAMTS-5 must be tightly regulated. On the occasion of the 20th anniversary of the discovery of ADAMTS-5, this review looks at the evidence for its detrimental role in OA, as well as its physiological turnover of cardiovascular proteoglycans. Moreover, the other potential functions of this enzyme are highlighted. Finally, challenges and emerging trends in ADAMTS-5 research are discussed.
Calcifying fibrous tumour: An IgG4-related disease or not?
Hu YH, Yu CT, Chen CJ … +1 more , Wen MC
Int J Exp Pathol · 2020 Feb · PMID 32090409 · Full text
Calcifying fibrous tumour (CFT) has some of the histopathological features, such as abundant plasma cells and stromal fibrosis, that are exhibited by IgG4-related diseases (IgG4-RD). The possible role of IgG4-positive pl...
Calcifying fibrous tumour (CFT) has some of the histopathological features, such as abundant plasma cells and stromal fibrosis, that are exhibited by IgG4-related diseases (IgG4-RD). The possible role of IgG4-positive plasma cells in calcifying fibrous tumour was investigated. The aim of this study was to determine any potential relationship between IgG4-RD and CFT. Thirteen cases with a total of 16 CFTs were reviewed. Lesion samples were immunostained with anti-IgG4 and anti-IgG antibodies. The number of IgG4-positive and IgG-positive plasma cells (IgG + PC) and their ratios were estimated. Plasma cells were found in all tumours. IgG4-positive plasma cells ranged from 0 to 71 per high-power field (HPF; mean 17.8/HPF), and IgG + PC ranged from 2 to 93/HPF (mean 42.6/HPF). The IgG4/IgG ratio ranged from 0% to 80% (mean 29%). There were seven tumours with the ratio of IgG4/IgG + PC that exceeded 40%. Various degrees of stromal fibrosis were present in eight tumours. All tumours have variable calcification. The histopathological features of CFT were found to be similar to those of IgG4-RD. Some CFT also showed a high number of IgG4-positive plasma cells, and the ratio of IgG4/IgG + PC exceeded 40%, most notably in patients with concomitant inflammatory or autoimmune disease. The long-term follow-up showed no evidence of IgG4-RD in any of these patients. Our findings suggest that while CFT overlaps morphologically with IgG4-RD, it probably should not be classified as an IgG4-RD.
miR-155 overexpression is followed by downregulation of its target gene, NFE2L2, and altered pattern of VEGFA expression in the liver of melanoma B16-bearing mice at the premetastatic stage.
Aksenenko MB, Palkina NV, Sergeeva ON … +3 more , Yu Sergeeva E, Kirichenko AK, Ruksha TG
Int J Exp Pathol · 2019 Oct · PMID 32043657 · Full text
MicroRNAs are involved in the control of tumour progression and in metastatic cascade dynamics. However, the role of microRNAs in distant organ reorganization at the premetastatic stage is less clear, although the proces...
MicroRNAs are involved in the control of tumour progression and in metastatic cascade dynamics. However, the role of microRNAs in distant organ reorganization at the premetastatic stage is less clear, although the process of premetastatic niche formation is a crucial event according to modern concepts of tumour dissemination. The role of the present study was to investigate the expression levels of miR-155, miR-21, miR-205 and miR-let7b, as well as that of their target genes, in target organs of melanoma metastasis at the premetastatic stage. The expression levels of both the pro-oncogenic miR-155 and the tumour suppressive miR-205 were found to be altered in the premetastatic liver of melanoma B16-bearing mice. Bioinformatics analysis identified the target genes of miR-155 to be nuclear factor, erythroid 2 like 2 (NFE2L2), secretogranin II, miR-205, semaphorin 5A and vascular endothelial growth factor A (VEGFA). Among those, the redox status regulatory factor NFE2L2 was downregulated, which corresponded to increased levels of miR-155. Due to the ability of pro-oxidative events to initiate angiogenesis, VEGFA levels were evaluated in the premetastatic liver by immunohistochemistry, which revealed increased VEGFA expression in the central parts of the organ and diminished expression in the periphery. Taken together, these findings may support the concept of functional organ reorganization due to melanoma progression.
Dysplastic urothelial changes accompany empagliflozin administration in urinary bladder of experimental diabetes.
Abdel-Hamid AAM, Firgany AEL
Int J Exp Pathol · 2019 Oct · PMID 32040227 · Full text
Empagliflozin (EMPA) is a promising novel antidiabetic drug; however, doubts have been raised regarding its use and the increased risk of urinary bladder carcinoma. In this study, we evaluated urothelium expression of cy...
Empagliflozin (EMPA) is a promising novel antidiabetic drug; however, doubts have been raised regarding its use and the increased risk of urinary bladder carcinoma. In this study, we evaluated urothelium expression of cytokeratins (CKs) and Ki-67 proliferative activity in the urinary bladder of diabetic (DM + EMPA) and non-diabetic rats after EMPA administration. By routine histology, dysplastic changes were detected in the urothelium of diabetic as well as non-diabetic animals after EMPA administration. Moreover, the expression of CK-7 and CK-8 was significantly decreased (P < .05) while that of CK-20 as well as Ki-67 was significantly increased (P < .05) in EMPA per se and DM + EMPA urothelium groups compared to that of control and diabetics. The dysplastic changes together with the increased proliferative activity in urothelium after EMPA administration provide a cellular evidence that supports the former clinical concerns.
Effects of mesenchymal stromal cells on motor function and collagen in the skeletal muscles of rats with type I diabetes.
Luna GLF, Russo TL, Sabadine MA … +5 more , Estrada-Bonilla YC, Andrade ALM, Brassolatti P, Anibal FF, Leal ÂMO
Int J Exp Pathol · 2019 Oct · PMID 32026546 · Full text
The present study aimed to evaluate the effects of mesenchymal stromal cell (MSC) transplantation on motor function and collagen organization in the muscles of rats with type 1 diabetes mellitus. Male Wistar rats were ra...
The present study aimed to evaluate the effects of mesenchymal stromal cell (MSC) transplantation on motor function and collagen organization in the muscles of rats with type 1 diabetes mellitus. Male Wistar rats were randomly assigned to three groups: control (C), diabetic (DM) and diabetic treated with MSCs (DM-MSCs). Diabetes was induced by streptozotocin (50 µg/kg). Bone marrow cells were isolated from the tibia and femur. After 10 weeks of DM induction, the DM-MSC rats received four i.p. injections of MSCs (1 × 106). Ten weeks after MSC transplantation, motor performance was evaluated by the rotarod test and the anterior tibial (TA) muscles were collected for morphometric and quantification of collagen birefringence by polarizing microscopy analysis. Motor performance of the DM group was significantly reduced when compared to the C group and increased significantly in the DM + MSC group. The TA muscle mass was significantly reduced in the DM and DM + MSC groups compared to the C group. The connective tissue increased in the DM group compared to the C group and decreased in the DM + MSC group. The percentage collagen birefringence decreased significantly in the DM group when compared to the C group and increased in the DM + MSC group. Motor performance was positively correlated with collagen birefringence and negatively correlated with percentage of connective tissue. The results indicate that MSC transplantation improves both motor function and the collagen macromolecular organization in type 1 DM.
The density of infiltrating T cells and macrophages in the parental tumour correlates with growth rate of tumoroids established from colorectal adenocarcinoma.
Mousavi N, Jespersen AJB, Jorgensen LN … +2 more , Timmermans V, Heegaard S
Int J Exp Pathol · 2019 Oct · PMID 31997501 · Full text
The aim of the present study was to investigate the correlation between the density of infiltrating T cells and macrophages in the parental colorectal cancer (CRC) and the growth rate of tumoroids (i.e. a patient-derived...
The aim of the present study was to investigate the correlation between the density of infiltrating T cells and macrophages in the parental colorectal cancer (CRC) and the growth rate of tumoroids (i.e. a patient-derived in vitro 3D model). Tumoroids were established from fresh specimens of primary and metastatic CRC from 29 patients. The in vitro growth rate of tumoroids was monitored by automated imaging. The density of infiltrating T cells and macrophages was determined in the centre of the tumour (CT) and at the invasive margin (IM) of the parental tumours. This was performed by digital image analysis on the whole-slide scanned images using Visiopharm software. Tumoroids with higher density of infiltrating CD3+ lymphocytes in the IM of their parental tumour showed a higher growth rate (P < .0005). The average relative growth rate (log10) during the period from day 1 to day 11 was 0.364 ± 0.006 (mean ± SD) for the CD3+ (IM)-high group and 0.273 ± 0.008 (mean ± SD) for the CD3+ (IM)-low group. In contrast, the density of CD68+ infiltrating macrophages in the parental tumours showed significant inverse effect on the growth rate of the tumoroids (P < .0005). The present study showed that the density of immune cells in the parental CRC correlates with the growth rate of the tumoroids. The future perspective for such a 3D model could be in vitro investigations of the tumour-associated inflammatory microenvironment as well as personalized cancer immunotherapy.
Hyponatraemia aggravates cardiac susceptibility to ischaemia/reperfusion injury.
Oniki T, Teshima Y, Nishio S … +5 more , Ishii Y, Kira S, Abe I, Yufu K, Takahashi N
Int J Exp Pathol · 2019 Oct · PMID 31994291 · Full text
Hyponatraemia is defined as a serum sodium concentration of <135 mEql/L and is the most common electrolyte disturbance in patients with chronic heart failure. We hypothesize that hyponatraemia may induce Ca overload and...
Hyponatraemia is defined as a serum sodium concentration of <135 mEql/L and is the most common electrolyte disturbance in patients with chronic heart failure. We hypothesize that hyponatraemia may induce Ca overload and enhance reactive oxygen species (ROS) production, which will exacerbate myocardial injury more than normonatraemia. We investigated the effect of hyponatraemia on the ability of the heart to recover from ischaemia/reperfusion episodes. Cardiomyocytes were obtained from 1- to 3-day-old Sprague Dawley rats. After isolation, cardiomyocytes were placed in Dulbecco's modified Eagle's medium (DMEM) containing low sodium concentration (110, 120, or 130 mEq/L) or normal sodium concentration (140 mEq/L) for 72 hours. Exposure of cardiomyocytes to each of the low-sodium medium significantly increased both ROS and intracellular Ca levels compared with the exposure to the normal-sodium medium. In vivo, 8-week-old male Sprague Dawley rats were divided into four groups: control group (Con), furosemide group (Fur), low-sodium diet group (Lsd) and both furosemide and low-sodium diet group (Fur + Lsd). The hearts subjected to global ischaemia exhibited considerable decrease in left ventricular developed pressure during reperfusion, and the size of infarcts induced by ischaemia/reperfusion significantly increased in the Fur, Lsd and Fur + Lsd compared with that in the Con. Hyponatraemia aggravates cardiac susceptibility to ischaemia/reperfusion injury by Ca overload and increasing in ROS levels.
Resveratrol attenuates cerebral ischaemia reperfusion injury via modulating mitochondrial dynamics homeostasis and activating AMPK-Mfn1 pathway.
Gao J, Wang H, Li Y … +1 more , Li W
Int J Exp Pathol · 2019 Oct · PMID 31867811 · Full text
The pathogenesis of cerebral ischaemia reperfusion injury (IRI) has not been fully described. Accordingly, there is little effective drug available for the treatment of cerebral IRI. The aim of our study was to explore t...
The pathogenesis of cerebral ischaemia reperfusion injury (IRI) has not been fully described. Accordingly, there is little effective drug available for the treatment of cerebral IRI. The aim of our study was to explore the exact role played by Mfn1-mediated mitochondrial protection in cerebral IRI and evaluate the beneficial action of resveratrol on reperfused brain. Our study demonstrated that hypoxia-reoxygenation (HR) injury caused N2a cell apoptosis and this process was highly affected by mitochondrial dysfunction. Decreased mitochondrial membrane potential, increased mitochondrial oxidative stress, and an activated mitochondrial apoptosis pathway were noted in HR-treated N2a cells. Interestingly, resveratrol treatment could attenuate N2a cell apoptosis via sustaining mitochondrial homeostasis. Further, we found that resveratrol modulated mitochondrial performance via activating the Mfn1-related mitochondrial protective system. Knockdown of Mfn1 could abolish the beneficial effects of resveratrol on HR-treated N2a cells. Besides, we also report that resveratrol regulated Mfn1 expression via the AMPK pathway; inhibition of AMPK pathway also neutralized the anti-apoptotic effect of resveratrol on N2a cells in the setting of cerebral IRI. Taken together our results show that mitochondrial damage is closely associated with the progression of cerebral IRI. In addition we also demonstrate the protective action played by resveratrol on reperfused brain and show that this effect is achieved via activating the AMPK-Mfn1 pathway.
Pro-inflammatory effects of extracellular Hsp70 on NCI-H292 human bronchial epithelial cell line.
Hulina-Tomašković A, Grdić Rajković M, Jelić D … +4 more , Bosnar M, Sladoljev L, Žanić Grubišić T, Rumora L
Int J Exp Pathol · 2019 Oct · PMID 31828837 · Full text
Extracellular Hsp70 (eHsp70) exerts its biological actions via Toll-like receptors 2 and 4, and is increased in sera of chronic obstructive pulmonary disease (COPD) patients. The aim of this study was to explore the pro-...
Extracellular Hsp70 (eHsp70) exerts its biological actions via Toll-like receptors 2 and 4, and is increased in sera of chronic obstructive pulmonary disease (COPD) patients. The aim of this study was to explore the pro-inflammatory effects and cytotoxicity of eHsp70 alone and in combination with bacterial components lipoteichoic acid (LTA) and lipopolysaccharide (LPS) on NCI-H292 airway epithelial cells. NCI-H292 cells were treated with recombinant human Hsp70 protein (rhHsp70), LPS, LTA and their combinations for 4, 12, 24 and 48 hours. IL-6, IL-8 and TNF-α levels were measured by an ELISA method. Cell viability was determined by the MTS method, and caspase-3/7, caspase-8 and caspase-9 assays. rhHsp70 induced secretion of IL-6 and IL-8 in a concentration- and time-dependent manner, with the highest secretion at 24 hours. rhHsp70 combined with LTA had antagonistic and with LPS synergistic effect on IL-6 secretion, while the interactions between rhHsp70 and LPS or LTA on IL-8 were synergistic. TNF-α was not detected in the applied conditions. rhHsp70, LPS or LTA did not affect cell viability, and rhHsp70 even suppressed caspase-3/7 activities. We suggest that pro-inflammatory effects of eHsp70, together with other damaging molecules and/or COPD risk factors, might contribute to the aggravation of chronic inflammation in human bronchial epithelium.
The effects of intravitreal H S application on apoptosis in the retina and cornea in experimental glaucoma model.
Erisgin Z, Ozer MA, Tosun M … +2 more , Ozen S, Takir S
Int J Exp Pathol · 2019 Oct · PMID 31777145 · Full text
One of the most important causes of visual loss (blindness) is glaucoma, which occurs due to the degeneration of the ganglion cells in retina. It has been shown that hydrogen sulphide (H S) acts an antioxidant, neuroprot...
One of the most important causes of visual loss (blindness) is glaucoma, which occurs due to the degeneration of the ganglion cells in retina. It has been shown that hydrogen sulphide (H S) acts an antioxidant, neuroprotective and neuromodulator and provides protection against oxidative stress and apoptosis. This study aims to examine through which apoptotic pathway H S acts in experimental glaucoma model. Twenty-two male wistar albino rats were used in this study. Group 1 (n = 6, control group): Intravitreal saline was given in the third week without inducing ocular hypertension (OHT) with laser photocoagulation. Group 2 (n = 8): After the induction of OHT with laser photocoagulation, intravitreal saline was given in the third week. Group 3 (n = 8): After the induction of OHT with laser photocoagulation, intravitreal H S's donor sodium hydrosulphide (NaSH) 100 nmol/L was given in the third week. At the end of the 6th week, the eyes of the rats were sacrified under anaesthesia and extracted and then routine tissue follow-up was undertaken. Besides haematoxylin & eosin (H&E) staining, Bax, Bcl-2, p53 and caspase-3 activation were examined immunohistochemically in the retina and the cornea. This showed that ocular hypertension caused apoptosis through the intrinsic pathway, due to Bax and caspase-3 activation, in both retina and cornea, and that this led to DNA damage due to p53 activation. Also, we found that H S exposure in glaucoma distinctly suppressed Bax, caspase-3 and p53 activations in retina but that it has a limited effect on the cornea. According to these results, glaucoma caused apoptosis in the retina through intrinsic pathway, and the damage to the retina could be compensated partially by H S but would have limited on the cornea.
British Society for Matrix Biology Spring 2019 Meeting: "Stroma, Niche, Repair".
Int J Exp Pathol · 2019 Aug · PMID 31769149 · Full text
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Immunohistochemical study of renal fibropoiesis associated with dogs naturally and experimentally infected with two different strains of Leishmania (L.) infantum.
Alves AF, Pereira RA, de Andrade HM … +2 more , Mosser DM, Tafuri WL
Int J Exp Pathol · 2019 Aug · PMID 31696580 · Full text
The objectives of this work were to study some pathological aspects of kidneys obtained from dogs naturally infected with Leishmania infantum and from dogs experimentally infected with two different strains of L infantum...
The objectives of this work were to study some pathological aspects of kidneys obtained from dogs naturally infected with Leishmania infantum and from dogs experimentally infected with two different strains of L infantum with special emphasis on fibrotic process. Seventy eight specimens of paraffin-embedded kidney fragments were collected as follows: (a) CNI group composed by 62 kidney samples of adult mongrel dogs, naturally infected with L infantum; (b) BH401 group composed by five kidney samples of adult Beagles experimentally infected with L infantum strain MCAN BR/2002/BH401; (c) BH400 group composed by eleven kidney samples of adult Beagles experimentally infected with L infantum strain MCAN/BR/2000/BH400, at the same dose and same route of the previous group, denominated group BH400; Control group (CC) composed by four kidney samples of adult Beagles. All animals revealed glomerular and interstitial fibropoiesis associated with different types of glomerulonephritis and chronic interstitial nephritis. Fibrosis was markedly more intense in the BH401 group, followed by animals in the CNI group. Markers for myofibroblasts (mesenchymal markers) such as alpha-actin (α-SMA), vimentin and the cytokine transforming growth factor beta (TGF-β) were done by immunohistochemistry. BH401 group showed higher expression of all these markers than others. Intracellular amastigotes forms of Leishmania was mainly found in BH401. These results could be indicating that the MCAN/BR/2002/BH401 strain is a good choice for the study of renal LVC experimental model.
Effect of irinotecan on the tongue mucosa of juvenile male albino rat at adulthood.
Ibrahim MAAH, Elwan WM
Int J Exp Pathol · 2019 Aug · PMID 31577062 · Full text
Irinotecan is one of the most important anti-tumour drugs against a broad spectrum of malignancies, but is known to be associated with possible oral complications. The aim of the present study was to evaluate the effect...
Irinotecan is one of the most important anti-tumour drugs against a broad spectrum of malignancies, but is known to be associated with possible oral complications. The aim of the present study was to evaluate the effect of irinotecan on the tongue mucosa of juvenile male albino rat at adulthood using different histological and immunohistochemical methods. Twenty juvenile male albino rats were divided equally into two groups: control and irinotecan-treated group (single injection of 200 mg irinotecan/kg, then kept for four weeks without treatment). The tongue specimens were processed for light microscopy and scanning electron microscopy. The irinotecan-treated group showed statistically significant shortening and thinning of the lingual papillae. There was loss of the normal appearance of the filiform papillae with focal cell loss alternating with areas of hyperkeratosis. Focal separation of the keratin layer, some nuclear changes and vacuolation of some epithelial cells were detected. Dilated congested blood vessels and mild mononuclear cellular infiltration were encountered. Atrophic fungiform papillae with ill-defined taste bud cells were observed. A statistically significant decrease in the pattern of Ki67 immunohistochemical staining reaction was detected in comparision to the control group. Scanning electron microscopy revealed different signs of atrophy of the tongue papillae. Focal areas of desquamation of lingual papillae were observed revealing some filiform papillae with desquamated surface, bisected tips and evident thinning. Some extravasated red blood cells could be detected. Thus irinotecan caused significant morphological and morphometrical alterations of the tongue mucosa in particularly the filiform papillae.
Origins of a pervasive, erroneous idea: The "green birefringence" of Congo red-stained amyloid.
Howie AJ
Int J Exp Pathol · 2019 Aug · PMID 31515863 · Full text
Congo red was discovered to stain amyloid by accident in 1922, and Congo red-stained amyloid was shown to be birefringent on polarization microscopy in 1927. Colours, namely green and yellow, were reported under these co...
Congo red was discovered to stain amyloid by accident in 1922, and Congo red-stained amyloid was shown to be birefringent on polarization microscopy in 1927. Colours, namely green and yellow, were reported under these conditions in 1945, although these are only two of various anomalous colours that may be seen, depending on the optical set-up. In 1953 there began a dogmatic insistence that in Congo red-stained amyloid between crossed polarizer and analyser green alone should be seen, and the finding of any other colour was a mistake. The idea that green, and only green, is essential for the diagnosis of amyloid has persisted almost universally, and virtually all mentions of Congo red-stained amyloid say that it just shows "green birefringence" or "apple-green birefringence." This idea is wrong and is contrary to everyday experience, because green is seldom seen on its own under these conditions of microscopy, and often, there is no green at all. How observers maintain this unscientific position is explained by a study of its historical origins. Most of the early literature was in German or French and was usually quoted in English at second hand, which meant that misquotations, misattributions and misunderstandings were common. Few workers reported their findings accurately, hardly any attempted to explain them, and until 2008, none gave a completely satisfactory account of the physical optics. The history of Congo red-stained amyloid is an instructive example of how an erroneous belief can become widely established even when it is contradicted by simple experience.
Sema3E is required for migration of cranial neural crest cells in zebrafish: Implications for the pathogenesis of CHARGE syndrome.
Liu ZZ, Guo J, Lu Y … +5 more , Liu W, Fu X, Yao T, Zhou Y, Xu HA
Int J Exp Pathol · 2019 Aug · PMID 31464029 · Full text
CHARGE syndrome is a congenital disorder with multiple malformations in the craniofacial structures, and cardiovascular and genital systems, which are mainly affected by neural crest defects caused by loss-of-function mu...
CHARGE syndrome is a congenital disorder with multiple malformations in the craniofacial structures, and cardiovascular and genital systems, which are mainly affected by neural crest defects caused by loss-of-function mutations within chromodomain helicase DNA-binding protein 7 (CHD7). However, many patients with CHARGE syndrome test negative for CHD7. Semaphorin 3E (sema3E) is a gene reported to be mutated in patients with CHARGE syndrome. However, its role in the pathogenesis of CHARGE syndrome has not been verified experimentally. Here, we report that the knockdown of sema3E results in severe craniofacial malformations, including small eyes, defective cartilage and an abnormal number of otoliths in zebrafish embryos, which resemble the major features of CHARGE syndrome. Further analysis reveals that the migratory cranial neural crest cells are scattered in the region of the hindbrain, and the postmigratory neural crest cells are reduced in the pharyngeal arches upon sema3E knockdown. Notably, immunostaining and time-lapse imaging analyses of a neural crest cell-labelled transgenic fish line, sox10:EGFP, show that the migration of cranial neural crest cells is severely impaired, and many of these cells are misrouted upon sema3E knockdown. Furthermore, the sox10-expressing cranial neural crest cells are scattered in chd7 homozygous mutants, which phenocopied the phenotype in sema3E morphants. Overexpression of sema3E rescues the phenotype of scattered cranial neural crest cells in chd7 homozygotes, indicating that chd7 may control the expression of sema3E to regulate cranial neural crest cell migration. Collectively, our data demonstrate that sema3E is involved in the pathogenesis of CHARGE syndrome by modulating cranial neural crest cell migration.
Effects of beta-hydroxy-beta-methylbutyrate supplementation on skeletal muscle in healthy and cirrhotic rats.
Holeček M, Vodeničarovová M
Int J Exp Pathol · 2019 Jun · PMID 31321841 · Full text
Beta-hydroxy-beta-methylbutyrate (HMB) is a leucine metabolite with protein anabolic effects. We examined the effects of an HMB-enriched diet in healthy rats and rats with liver cirrhosis induced by multiple doses of car...
Beta-hydroxy-beta-methylbutyrate (HMB) is a leucine metabolite with protein anabolic effects. We examined the effects of an HMB-enriched diet in healthy rats and rats with liver cirrhosis induced by multiple doses of carbon tetrachloride (CCl4). HMB increased branched-chain amino acids (BCAAs; valine, leucine and isoleucine) in blood and BCAA and ATP in muscles of healthy animals. The effect on muscle mass and protein content was insignificant. In CCl4-treated animals alterations characteristic of liver cirrhosis were found with decreased ratio of the BCAA to aromatic amino acids in blood and lower muscle mass and ATP content when compared with controls. In CCl4-treated animals consuming HMB, we observed higher mortality, lower body weight, higher BCAA levels in blood plasma, higher ATP content in muscles, and lower ATP content and higher cathepsin B and L activities in the liver when compared with CCl4-treated animals without HMB. We conclude that (1) HMB supplementation has a positive effect on muscle mitochondrial function and enhances BCAA concentrations in healthy animals and (2) the effects of HMB on the course of liver cirrhosis in CCl4-treated rats are detrimental. Further studies examining the effects of HMB in other models of hepatic injury are needed to determine pros and cons of HMB in the treatment of subjects with liver cirrhosis.
Does gender influence cardiovascular remodeling in C57BL/6J mice fed a high-fat, high-sucrose and high-salt diet?
Pereira-Silva DC, Machado-Silva RP, Castro-Pinheiro C … +1 more , Fernandes-Santos C
Int J Exp Pathol · 2019 Jun · PMID 31321834 · Full text
Animal models are widely used to study the physiopathology of human diseases. However, the influence of gender on modern society diet style-induced cardiovascular disease has not thus far been explored in these models. T...
Animal models are widely used to study the physiopathology of human diseases. However, the influence of gender on modern society diet style-induced cardiovascular disease has not thus far been explored in these models. Thus, this study investigated cardiovascular remodelling in C57BL/6J mice fed a diet rich in saturated fat, sucrose and salt, evaluating gender effect on this process. Male and female C57BL/6J mice were fed AIN93M diet or a modified AIN93M rich in fat, sucrose and salt (HFSS) for 12 weeks. Body mass, water and food intake and cardiovascular remodelling were assessed. The HFSS diet did not lead to body mass gain or glucose metabolism disturbance as assessed by serum glucose, insulin and oral glucose tolerance test. However, female mice on a HFSS diet had increased visceral and subcutaneous adiposity. Only male mice displayed heart hypertrophy. The left ventricle was not hypertrophied in either male or female mice, but its lumen was dilated. Intramyocardial arteries and the thoracic aorta showed media thickening in male mice, but in the female it was only observed in the thoracic aorta. Finally, intramyocardial artery dilation was present in both genders, but not in the aorta. Therefore changes in LV dimensions and arterial remodelling were influenced by both gender and the HFSS diet. In conclusion, male and female C57BL/6J mice suffered cardiovascular remodelling after 12 weeks of HFSS feeding, although they did not develop obesity or diabetes. Sexual dimorphism occurred in response to diet for body adiposity, heart hypertrophy and intramyocardial artery remodelling.
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