DigitalUM :: Browsing by Subject "Histopathology"

Browsing by Subject "Histopathology"

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Open Access
A clinicopathologic study of paragangliomas of the urinary bladder: can the clinical behavior of the tumor be predicted?
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Guo, Shuangping; Fan, Chaoliang; Rohr, Joseph; Fan, Linni; Wang, Yingmei; Li, Mingyang; Li, Xia; Guo, Ying; Yan, Qingguo; Wang, Lu; Wang, Zhe
Paraganglioma of the urinary bladder is rare but even more unusual as no singular histologic feature is consistently characteristic of malignancy. Additionally, paragangliomas can manifest in hypertensive crisis for clinicians resecting the tumors in unusual locations without proper histologic diagnosis. Herein we report nine cases of paraganglioma of the urinary bladder with immunohistologic study and follow-up information, including one rare malignant case with liver metastasis. Comparison of the immunohistologic features reveal that the malignant case shows the common features suggested by both the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and Grading of Adrenal Pheochromocytoma and Extraadrenal Paraganglioma (GAPP) system. The predominant histopathologic features of malignant cases were large irregular nests with focal spindle tumor cells and a diffusely infiltrative growth pattern between smooth muscle of the urinary bladder wall with multiple necrotic areas and a high proliferative index. Eight cases without metastasis showed the classic zellballen of benign paragangliomas without irregular nests and welldemarcated nodules either in the submucosa or between smooth muscle bundles with no diffuse infiltration. We discuss the histopathologic and immunohistochemical features detecting malignant behavior, and comprehensively review the previously published cases of malignant paraganglioma of the urinary bladder. In summary, we assess some clinicopathologic features which might help to predict which neoplasms are more likely to behave in a clinically aggressive manner to avoid adverse outcomes in this rare tumor’s resection.
Open Access
Acinar cell carcinoma of the pancreas. A histologic, immunocytochemical and ultrastructural study
(Murcia : F. Hernández, 1994) Caruso, R.A.; Inferrera, A.; Tuccari, G.; Barresi, G.
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Open Access
Biochemical and histopathological changes in the mortality caused by acute ischemic limb injury: a rabbits' model
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 1998) Sun, J. S.; Tsuang, Y. H.; Lu, F. J.; Lu, K. S.; Hang, Y. W.
Restoration of blood flow to an acute ischemic extremity may deteriorate the ischemic injury, lead to multiple organ dysfunction or even death. This paradox of continuing injury during reperfusion is not completely understood. The role of multi-organ damage in the mortality caused by ischemic limb injury is also still not clarified. The purpose of this study is to determine the biochemical and histopathological changes in the mortality caused by ischemic limb injury. After anesthesia, the hindlimbs of 14 New Zealand white rabbits were made ischemic and set into 8 hours or 12 hours of ischemia. Blood samples were obtained then the creatine kinase (CK) levels were determined and CK isoenzymes analyzed. All rabbits with 8 hours' ischemia survived well , and 5 of the 7 rabbits with 12 hours' ischemia expired within 8 hours after reperfusion. CK elevation was correlated most strongly with the time of the ischemic insults. The percentage of CK-MB isoenzyme remained unchanged after 8 hours' ischemiareperfusion insult, while increased significantly after 12 hours' ischemia-reperfusion insult. Histologic examinations showed that the major systemic manifestation was massive destruction of the liver and kidney. The injuries are more obvious in areas with the greatest blood flow during reperfusion. We concluded that the ratio of CK-MB isoenzyme is most useful for distinguishing the risk of mortality caused by acute ischemic limb injury, and the cause of systemic complications are attributed to the multi-organ failure .
Open Access
Bone marrow engraftment: histopathology of hematopoietic reconstitution following allogeneic transplantation in CML patients
(Murcia : F. Hernández, 2001) Thiele, J.; Kvasnicka, H.M.; Beelen, D.W.; Leder, L.D.; Schaefer, U.W.
Following myelo-ablative treatment and allogeneic bone marrow transplantation (BMT) in chronic myelogenous leukemia (CML) histopathological features assumed to exert a sienificant i m ~ a c ot n engraftment have been rarely inve;igated systekatically. This review is focused on immunohistochemical and morphometric techniques involving nucleated erythroid precursors, resident macrophages and their various subsets, megakaryocytes and finally argyrophilic (reticulin-collagen) fibers. Regarding standardized intervals of examination in the postgraft sequential trephine biopsies a pronounced reduction in cellularity was obvious and accompanied by a decrease in the quantity of erythro- and megakaryopoiesis. A significant correlation between the number of erythroid precursors and CD68+-macrophages could be determined in the areas of regenerating hematopoiesis. This finding is in keeping with the important functional role of the centrally localized mature macrophages during erythropoiesis. A relevant pretransplant reduction of the red cell lineage and an early to advanced reticulin fibrosis were correlated with a low hemoglobin leve1 (anemia) and splenomegaly and furthermore associated with a significant delay to reach transfusion independence. This result was supported by corresponding findings in biopsy specimens performed shortly after day 30 following BMT (standard interval for assessment of engraftment). Samples revealed an enhancement of fiber density and a conspicuous decrease in the amount of erythropoiesis in the small fraction of patients who did not conform with the usually accepted criteria for successful hematopoietic reconstitution. Considering the compartment of histiocytic reticular cells the recurrence of Pseudo-Gaucher cells (PCGs) in the engrafted donor marrow was remarkable and most prominently expressed in the first two months following BMT. This feature was presumed to be functionally linked with a pronounced degradation of cell debris in the seque1 of myelo-ablative therapy (scavenger macrophages). According to planimetric measurements in the postgraft bone marrow the atypical dwarf-like CD61+-megakaryocytes characteristic for CML disappeared. On the other hand, normalization of megakaryocyte size and nuclear lobulation were absent in sequential examination of the few patients developing a leukemic relapse. In a number of patients with manifest myelofibrosis at onset, an initial regression after BMT was followed by an insidiously occurring retrieval which was concentrated on the areas of reconstituting hematopoiesis. Similar to its relevant pretransplant association the postgraft reappearance of myelofibrosis was significantly correlated with the quantity of CD61+-megakaryocytes. Altogether a number of histological features in the pre-and postgraft bone marrow exhibited significant correlations with each other and thus indicated functional relationships. Moreover, quantity of erythropoiesis and amount of reticulin fibers (myelofibrosis) exerted a significant impact on engraftment status.
Open Access
Bone marrow histopathology in chronic myelogenous leukemia ,CML, evaluation of distinctive features with clinical impact
(Murcia : F. Hernández, 1999) Thiele, J.; Kvasnicka, H.M.; Fischer, R.
Bone marrow features in stable-phase chronic myelogenous leukemia (CML) are characterized by a striking heterogeneity which is determinable by appropriate means including representative pre-treatment trephine biopsies, immunohistochemistry and morphometry. Cell lineages involved to a variable extent consist not only of neutrophil granulopoiesis, but include also megakaryocytes, erythroid precursors, resident macrophages and lymphocytes. Moreover, the stromal compartment, in particular reticulin and collagen fibers, plays a pivotal role in the disease process. Following morphometric analysis significant correlations may be calculated between histological parameters and clinicallaboratory findings. Relevant interactions are detectable between number of megakaryocytes and their precursors with fiber density. This finding is in line with the close functional relationships between megakaryopoiesis and fibroblasts regarding the complex pathomechanisms of myelofibrosis. Moreover, other correlations are observable between reduction of erythropoiesis or increase in fibers with clinical features like anemia, percentages of myelo- and erythroblasts in the peripheral blood, spleen size or LDH level. These variables are in keeping with more advanced stages of CML which indicate a transition to myeloid metaplasia and thus exert a significant impact on survival. Consequently, the different risk profiles of patients are determined by both clinical and morphological parameters of predictive value. Regarding the latter, extent of myelofibrosis, amount of erythroid precursors and numbers of myeloerythroblasts in the peripheral blood are significantly associated with prognosis. For this reason, it should be mandatory to enter morphological criteria into prospective clinical trials on CML, not only for diagnotic purpose, but also for a proper evaluation of different survival patterns.
Open Access
Diagnostic impact of bone marrow histopathology in polycythemia vera (PV)
(Murcia : F. Hernández, 2005) Thiele, J.; Kvasnicka, H.M.
The criteria of the Polycythemia Vera Study Group (PVSG), although acknowledged as the gold standard to establish the diagnosis of polycythemia vera (PV), do not regard bone marrow (BM) histopathology. Arguments include the existence of sufficient objective markers of disease and the lack of independently performed morphological studies or standardized criteria. The aim of this review is to evaluate morphological characteristics of erythrocytosis and to determine whether distinctive patterns of histopathology exist. A review of the pertinent literature and evaluation of 334 patients from our files with a borderline to marked increase in hemoglobin was performed. In extension to former descriptions of BM features by the PVSG, a tri-lineage myeloproliferation (panmyelosis) with a pleomorphous appearance of megakaryopoiesis revealed that, besides increase in size, there was a lack of gross cytological anomalies. Differentiation from secondary polycythemia (SP) was accomplished by regarding these features and the conspicuously expressed stromal changes (plasmacytosis, eosinophils, cell debris and iron deposits). In about 96% of this cohort a clearcut separation from SP was achieved, even in the initial (latent) stages. When accompanied by an elevated platelet count, these precursor stages may clinically mimick essential thrombocythemia because they are not recognized by the conventional criteria. Advanced stages (spent phases) of PV were consistent with an increased left-shifted granulocytic proliferation, accompanied by reduction of erythroid precursors and progressive myelofibrosis (post-polycythemic myeloid metaplasia). Finally, an increase in dysplastic changes and immaturity signalled a transition into blastic crisis. In conclusion, PV is characterized by a distinctive pattern of histopathology that has been gained in an independent and blind fashion and therefore, dissolves arguments about failing specificity.
Open Access
Differential expression of ferroptosis markers, circadian regulators, KLOTHO, and classical tumor suppressors in colorectal cancer according to tumor stage: Influence of age, anatomical location, and correlation patterns
(2025) Cielo Garcia Montero; Oscar Fraile Martinez; Ana M. Minaya Bravo; Diego Liviu Boaru; Diego De Leon Oliva; Patricia De Castro Martinez; Majd N. Michael Alhaddadin; Silvestra Barrena Blázquez; Laura Lopez Gonzalez; Luis G. Guijarro; Natalio Garcia Honduvilla; Víctor Roberto Baena Romero; Carlos Daniel Padilla Ansala; Mar Royuela; María Del Val Toledo Lobo; Leonel Pekarek; Roberto Fernández Baillo Gallego de la Sacristana; Mauricio Hernández Fernández; Montserrat Chao Crecente; Melchor Alvarez-Mon; Raul Diaz-Pedrero; Miguel A. Ortega; Miguel A. Saez; Biología Celular e Histología
Colorectal cancer (CRC) is a leading cause of cancer-related mortality, with an incidence projected to rise significantly worldwide. While TNM staging remains the cornerstone of prognosis and treatment decisions, additional biomarkers are needed to enhance predictive accuracy and therapeutic targeting. Ferroptosis, an iron-dependent cell death pathway, has emerged as a key regulator of CRC progression and therapy resistance. Circadian rhythms, KLOTHO, and tumor suppressors, such as p53, CDKN1A (p21), and Rb, also play crucial roles in CRC biology. Integrating TNM staging with molecular markers and patient-specific variables offers a more precise, personalized approach to CRC management. In the present work, we analyze the histopathological expression of KLOTHO, ferroptosis markers (TFRC, ALOX-5, ACSL-4, and GPX-4), circadian regulators (CLOCK, BMAL1, PER1, and PER2), and classical tumor suppressors (p53, p21, and Rb) in a cohort of 63 patients diagnosed with CRC. Besides, we have considered important clinical variables, like sex, age, and anatomical location, in our statistical analysis; correlation with the protein expression of these markers was also included for each stage (T1, T2, and T3). Our study reveals that advanced CRC stages (primarily T3) exhibit increased expression of ferroptosis markers (TFRC, ALOX5, ACSL4, and GPX4) and tumor suppressors (p53, p21, and Rb), alongside reduced histopathological detection of KLOTHO and circadian markers (BMAL1, CLOCK, PER1, and PER2) compared with earlier stages. Age, but not sex, influenced the expression of several markers. Tumor location also played a role, with right-sided CRCs showing significant stage-related differences in ferroptosis, tumor suppressor, and BMAL1, whereas left-sided tumors exhibited variations primarily in circadian markers (CLOCK, PER1, and PER2). Correlation analyses across tumor stages indicate dynamic shifts, with tumor suppressors maintaining positive associations with ferroptosis markers and anti-aging/circadian markers showing stage-dependent changes. Despite the inherent limitations of our study, these findings highlight the evolving biomarker landscape in CRC progression, although further research is needed to elucidate their clinical implications.
Open Access
Domestic microwave processing for rapid immunohistochemical diagnosis of bovine rabies
(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Abreu, Camila C.; Nakayama, Priscilla A.; Nogueira, Clayton I.; Mesquita, Leonardo P.; Lopes, Priscila F.R.; Varaschin, Mary S.; Seixas, Josilene do N.; Ferreira, Enio; Bezerra Jr, Pedro S.
The present study describes the use of a microwave processing protocol for the rapid histopathological and immunohistochemical diagnosis of bovine rabies. Immunohistochemistry has been used for rabies diagnosis in formalin-fixed tissue with satisfactory results, although the time to diagnosis is considerably longer than that with direct immunofluorescence. The protocol provided a provisory histopathological rabies diagnosis in approximately three and half hours and the immunohistochemical diagnosis was available after six hours. The protocol achieved 100% correlation with direct immunofluorescence and is a promising method, particularly in situations in which only material in formalin is available for diagnosis or when the refrigeration or transportation of biological material is difficult.
Open Access
Effects of in utero exposure to low dose ionizing radiation on development in the rat
(Murcia : F. Hernández, 1994) Bruni, J.E.; Persaud, T.V.N.; Froese, G.; Huang, W.
Most studies of in utero effects of ionizing irradiation involve high doses and examination at postnatal intervals. Little information is available on the effects of low levels of ionizing radiation on embryogenesis. The developmental effects of in utero exposure to 50 cGy gamma radiation on gestational day-9.5 was investigated using Sprague- Dawley rats. Irradiated rats and appropriate controls were killed at prenatal intervals of 4h, 48h and 10 days after exposure. Fetuses were examined for abnormalities and random samples of tissues were prepared for microscopic study. With the exception of the neuroepithelium, no histopathological changes were observed in embryos 4h after exposure to 50 cGy. In irradiated embryos, mitoses were reduced within the neuroepithelium; pyknosis and some necrosis of cells were apparent at this gestational interval. Among the gross developmental abnormalities observed in embryos 48h after irradiation, excessive flexion of the embryo and abnormal flexion of the head were the only ones that appeared to be radiation-induced. The mean numerical score (47.310.2, controls; 42.410.1, irradiated) for 17 morphological parameters examined in fetuses at this gestational period compares favorably with other studies. Controls, however, showed greater variability in the extent of development of their forebrain, olfactory system, midbrain, hindbrain, and caudal neural tube. In al1 cases, there was evidence of slower development in these regions compared to their irradiated counterparts. At term. no significant differences in litter size or resorption rates were observed in irradiated animals compared to the controls, but there was a higher incidence of defective eye development, spinal curvature and visceral anomalies. In utero exposure to 50 cGY gamma-radiation during the period of early organogenesis can produce some irreversible defects that are discernible at term.
Open Access
Evaluation of the impact of Momordica charantia on the testis of cisplatin-treated albino rats: Biochemical, histopathological, and ultrastructural study
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Shalaby, Fatma Mohsen; Elrefaie, Amany Omar; Abd, Kandil; Attia, El Hai; Biología Celular e Histología
Cisplatin is an antineoplastic drug that exhibits toxicity dependent on dosage and has adverse reproductive effects. Momordica charantia (Bitter melon) is a natural vegetable plant; its active ingredients possess antioxidant, apoptotic, antiproliferative, hypoglycemic, and other therapeutic properties. This study evaluates the effect of the administration of bitter melon extract, cisplatin, and cisplatin/bitter melon cotreatment on liver and kidney functions, serum and testicular oxidative status, testis histology, and sperm parameters. Adult male Wistar rats were randomly divided into four groups: Group I (Control) received normal saline, Group II received oral bitter melon extract (300 mg/kg), Group III received cisplatin (2.5 mg/kg), and Group IV received the same doses of cisplatin and bitter melon, for six successive weeks, daily. Our results showed that bitter melon extract stimulates antioxidant enzymes and has anti-lipid peroxidation properties through the significantly increased plasma levels of glutathione and significantly decreased testicular malondialdehyde. The cisplatin-treated group showed oxidative stress indicated by the significant decrease of catalase, glutathione, and superoxide dismutase levels and a significant increase in malondialdehyde levels in both serum and testis compared with the control group. In the cisplatin/bitter melon-cotreated group, there was a significant increase in superoxide dismutase and a significant decrease in malondialdehyde in both serum and testis compared with cisplatin-treated rats. The bitter melon alone or with cisplatin cotreatment resulted in reduced gonadosomatic index, sperm count, motility, and viability. These results were confirmed by histopathological examinations, apoptosis assay using flow cytometry, and immunohistochemical staining for proliferating cell nuclear antigen. In conclusion, the administration of bitter melon extract alone or in combination with cisplatin led to testicular structure disturbances and showed an anti-spermatogenic effect. These findings are likely due to a combination of inhibited cellular proliferation, increased cell death, minor decrease in testosterone levels, and localized oxidative stress that outweigh the antioxidant benefits of bitter melon extract.
Open Access
Functional histopathology of keloid disease
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Jumper, N.; Paus, R.; Bayat, A.
Keloid disease is a benign, yet locally aggressive and recurrent cutaneous fibroproliferative condition characterised by excessive scarring. Unique to humans, keloids represent the end-point of a spectrum of abnormal wound healing, are aesthetically disfiguring and can cause major functional impairment. Its heterogeneous phenotype can confound clinical diagnosis leading to mismanagement. This review examines the histological morphology of keloid disease relative to the underlying pathobiology, places it in the context of other cutaneous fibroses and highlights gaps within the literature that hinder differential diagnosis. The pathological similarity to hypertrophic scarring, dermatofibrosarcoma protuberans, dermatofibroma and scleroderma emphasise the importance of detailing the architectural and cellular components of this unique entity. In the papillary dermis keloid tumours show a tongue-like advancing edge that resembles invasive tumour growth. A thickened but flattened epidermis, hyalinised haphazardly arranged collagen bundles that dominate the dermis with subsequent obliteration of the papillary-reticular boundary along with displacement and eventually destruction of skin appendages, exemplify additional hallmark findings associated with keloid disease. Compared to healthy skin, keloid scars show an increased type I/III collagen ratio, decreased fibrillin-1 and decorin expression, increased dermal cellularity and increased expression of fibronectin, versican, elastin and tenascin in the reticular dermis and hyaluronan and osteopontin in the epidermis. We illustrate these “pathognomonic” features of keloid disease by representative micrographs and discuss them in the context of inflammation, hypoxia and tension - as key elements of keloid disease. Finally, we highlight deficits within the keloid research literature as well as discuss important areas for future research in keloid histology.
Open Access
Histological changes and Micronucleus induction in the Zebra mussel Dreissena polymorpha after Paraquat exposure
(Murcia : F. Hernández, 2006) Mantecca, P.; Vailati, G.; Bacchetta, R.
The herbicide paraquat (PQ), still widely used in developing countries, represents a serious risk factor for human and environmental health. To test the sublethal effects of PQ on the freshwater bivalve Dreissena polymorpha, mussels were exposed to 0.125, 0.250, 0.500 mg/L for 7 and 14 days and histologically screened. PQ’s genotoxic potential was also determined in haemocytes by the micronucleus, MN, assay. At concentrations ³ 0.250mg/L, severe lesions, such as cellular vacuolation, lysis and thinness of the germinative epithelia were observed in the digestive gland and testis. A positive trend between the number of granulocytes and all PQ concentrations was observed in both gonads and digestive glands, addressing the inflammatory capacity of this herbicide on these tissues. Mussels exposed to PQ also exhibited a significant MN induction. The spontaneous MN frequencies ranged from 2.75 to 4.25‰, while PQ-induced MN rates in treated mussels were between 3.50 and 12.50‰. The histopathological effects on the digestive and reproductive systems, as well as the MN induction in the haemocytes, confirmed the cytotoxic and genotoxic effects of PQ also in D. polymorpha.
Open Access
Histological diversity of anti-PD1-induced colitis
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Sakellariou, Stratigoula; Papathanasiou, Evgenia; Perdiki, Marina; Sotiropoulou, Maria; Zampeli, Evangelia; Michopoulos, Spyros; Bamias, Giorgos; Delladetsima, Ioanna
Aim. Histological data on anti-PD1- associated colitis are limited, while the colitis subtypes are still not clearly defined and different terms are being used. The aim of the study was to explore the histopathology of anti-PD1-induced colitis. Methods and Results. Colonic biopsies from 9 patients under anti-PD1 agents presenting diarrhea were examined. Histological evaluation revealed colitis of mild to moderate severity in almost all cases. Four distinct dominant histological patterns were identified with nearly the same incidence: Ulcerative colitis (UC)- like (n=2), GVHD-like (n=2), collagenous-like (n=3) and a mixed colitis pattern combining features of microscopic and UC-like colitis (n=2). The latter was additionally characterized by high crypt epithelium apoptosis and cryptitis with mixed inflammatory infiltrate. Thickening of the subepithelial band of collagen, detachment of the surface epithelium and increased apoptosis of the crypt epithelium were commonly encountered features, irrespective of colitis subtype. CD4/CD8 ratio was lower in the “combined” and higher in the GVHD-like subtype. Conclusions. Anti-PD1-induced colitis is expressed by different patterns of injury which share distinct histological hallmarks harboring diagnostic value, while a “combined” colitis subtype is being established. The histological alterations are indicative of mucosa barrier damage after ant-PD1 treatment and its participation in the pathogenetic process
Open Access
Histopathological alterations in mice under sub-acute treatment with Hintonia latiflora methanolic stem bark extract
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Flores Jiménez, Nancy G.; Rojas Lemus, Marcela; Fortoul, Teresa I.; Zepeda Rodríguez, Armando; López Camacho, Perla Y.; Anacleto Santos, Jhony; Malagón Gutiérrez, Filiberto; Basurto Islas, Gustavo; Rivera Fernández, Norma
The indiscriminate use of herbal products is increasingly growing worldwide; nonetheless consumers are not warned about the potential health risks that these products may cause. Hintonia latiflora (Hl) is a tree native to the American continent belonging to the Rubiaceae family and its stem bark is empirically used mainly to treat diabetes and malaria; supplements containing Hl are sold in America and Europe without medical prescription, thus scientific information regarding its toxicity as a consequence of a regular consumption is needed. In the present study, the histopathological effect of 200 and 1000 mg/kg of Hl methanolic stem bark extract (HlMeOHe) was evaluated in the small bowel, liver, pancreas, kidneys and brain of CD-1 male mice after oral sub-acute treatment for 28 days. No histopathological alterations were observed in the brain of the treated animals; however, mice presented diarrhea from day 2 of treatment with both doses. No histological changes were observed in the tissues collected from the animals treated with 200 mg/kg, except for the liver that depicted periportal hepatitis. Animals treated with the higher dose showed in the liver sections hydropic degeneration, hepatitis and necrosis small bowel sections showed dilated mucosal vessels, kidney sections depicted tubular necrosis and in pancreas sections, hydropic degeneration of the pancreatic islets was observed. In conclusion, HlMeOHe damaged the liver with an oral dose of 200 mg/kg, and at 1000 mg/kg injured the kidneys and pancreas of the CD1 male mice.
Open Access
Histopathological alterations, EROD activity, CYP1A protein and biliary metabolites in gilthead seabream Sparus aurata exposed to Benzo(a)pyrene
(Murcia : F. Hernández, 2007) Ortiz-Delgado, J.B.; Segner, H.; Arellano, J.M.; Sarasquete, C.
This study compared for seabream, Sparus aurata exposed to benzo(a)pyrene-B(a)P-, the response of molecular cytochrome P450 1A (CYP1A) and cellular histopathology biomarkers. Male gilthead seabream, Sparus aurata specimens were exposed for 20 days via water to a series of high B(a)P concentrations. CYP1A was assessed by measuring enzymatic activity (EROD) and CYP1A protein content, and cellular responses were evaluated by routine histopathological methods. In addition, biliary metabolites were measured in order to verify that B(a)P was absorbed and metabolised. Histological lesions, both in liver and gills, increased in parallel to B(a)P concentrations, with the majority of changes representing rather non-specific alterations. Hepatic EROD and CYP1A proteins data showed a concentration-dependent induction, while in the gills, EROD activity but not CYP1A proteins showed a nonmonotonous dose response, with a maximum induction level at 200 μ g B(a)P.L-1 and decreasing levels thereafter. The findings provide evidence that short-term, high dose exposure of fish can result in significant uptake and metabolism of the lipophilic B(a)P, and in pronounced pathological damage of absorptive epithelia and internal organs.
Open Access
Histopathological changes in the islets of Langerhans in hamsters infected with the 139H strain of scrapie: semi-thin section study
(Murcia : F. Hernández, 1996) Ye, X.; Carp, R.I.
Using histopathological analysis of semi-thin sections stained with toluidine blue, we observed profound pathological changes in the islets of Langerhans of hamsters infected with the scrapie agent (strain 139H). These included cytoplasmic vesicles, nuclear swelling, and vacuolization in the islet cells. Two types of vacuolization were seen. "Localized vacuolization" (LV) has a distinct edge and is restricted or confined within the cell. "Diffuse vacuolization" (DV) has no distinct edge and is scattered within tissues either inside or outside of cells. DV may span intracellular and extracellular regions of the islet tissues. There were abnormal structures which we temed blood vessel cores (BVCs) in the islets of 139H-infected hamsters. BVC is a hollow space filled up with blood cells. Immunocytochemical staining for insulin antibody suggested that BVC was surrounded by the B cells of the islet. In the present study, we observed that many inflammatory cells passed through the blood-tissue barriers using pathways between cell-junction in the lumen of BVC. We also observed many necklace-like hollow spaces between islet cells. They are the pockets of extracellular space. A novel concept of "the accordion effect" was described to explain a function of the extracellular space. Under normal physiological conditions, as the synthesis of insulin increase in B cells, the volume of the B cells will increase while the volume of the extracellular space will decrease. After a synchronized secretory response from the stimulated B cells, the secretory product would move from the intracellular space into the extracellular space, the volume of the B cells would be decreased and the volume of the extracellular space would be increased. Most of the secretory product might be released into the blood stream immediately, causing an insulin releasing peak in the blood stream, whereas the rest would remain in the enlarged extracellular space. As the cycle repeat, the increasing volume of the B cells will squeeze the remaining insulin into the blood stream gradually. Thus, the expandable extracellular space would serve as buffer system and a reservoir to collect and store some secretory products for future use. We refer to this concept as "the accordion effect". The concept of "the accordion effect" may also be true in other endocrine organs such as pituitary gland and adrenal gland.
Open Access
Histopathological characteristics of adenomyosis: structure and microstructure
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2023) Liu, Ziyu; Guo, Yanxian; Pan, Xinyi; Yang, Xing
Adenomyosis is a benign uterine disease that pathologically shows endometrial glands and stroma in the myometrium. There are multiple lines of evidence that adenomyosis is associated with abnormal bleeding, painful menstruation, chronic pelvic pain, infertility, and spontaneous pregnancy loss. Pathologists have researched adenomyosis by studying tissue specimens from its first report more than 150 years ago, and differing viewpoints on its pathological alterations have been advanced. However, the gold standard histopathological definition of adenomyosis remains controversial to date. The diagnostic accuracy of adenomyosis has steadily increased due to the continual identification of unique molecular markers. This article provides a brief description of the pathological aspects of adenomyosis and discusses adenomyosis categorization based on histology. The clinical findings of uncommon adenomyosis are also presented to offer a thorough and detailed pathological profile. Furthermore, we describe the histolog
Open Access
Histopathological characteristics of liver biopsy performed at different time points in drug-induced liver injury
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Wang, Yu; Ma, Zikun; Guo, Tiantian; Liu, Jimin; Li, Min; Zhao, Xinyan
Background and Aims. Liver biopsy can provide critical information in patients with druginduced liver injury (DILI). Our study aimed to compare the histopathological features of DILI at different time points from the onset to liver biopsy. Methods: We conducted a single-centre retrospective observational study. The clinical and follow-up data were extracted, and the pathological slides were reviewed. Results. 129 patients were included. The median age was 52 and 75% were women. They were divided into <1 month, 1-3 months, and >3 months groups according to the durations from onset of the disorder to liver biopsy. The aminotransferase, alkaline phosphatase, and bilirubin levels showed no significant differences at onset but significantly decreased with time among the three groups (all p<0.05) at the time of liver biopsy. Histological injury patterns were significantly different among the three groups (p<0.01). Hepatocellular, canalicular, and cholestasis of Kupffer cells were significantly less frequent in the >3 months group (p<0.01). For patients taking herbs, bridging necrosis and cholestatic injury were significantly more frequent in the <1 month group (p<0.01). Furthermore, ductopenia, cholate stasis, and foam-like cells were equally distributed in the three groups but were significantly associated with poor prognosis. Conclusions. Biopsy time significantly affects liver pathology: the earlier, the more acute cholestatichepatitic pattern, the later, the more chronic injury patterns. The prognostic features (ductopenia, cholate stasis, and foam-like cells) occurred equally in all three groups. Our study provides valuable information for liver pathologists aiding in their better interpretation of the liver biopsy from patients with DILI.
Open Access
Histopathological effect of pterostilbene as chemoprevention in N-nitroso-tri-chloroethylurea (NTCU)-induced lung squamous cell carcinoma (SCC) mouse model
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Surien, Omchit; Ghazali, Ahmad Rohi; Masre, Siti Fathiah
ackground. Lung cancer is the leading cause of cancer-related deaths, and squamous cell carcinoma (SCC) is one of the most common types of lung cancer. Chemoprevention of lung cancer has gained increasing popularity as an alternative to treatment in reducing the burden of lung cancer. Pterostilbene (PS) may be developed as a chemopreventive agent due to its pharmacological activities, such as anti-proliferative, anti-inflammatory and antioxidant properties. This study aimed to investigate the effect of PS on the development of lung SCC in the mouse model. Methods. A total of 24 seven-week-old female Balb/C mice were randomly categorised into four groups, including two control groups comprising the N-nitroso-trischloroethylurea (NTCU)-induced lung SCC and vehicle control (VC) groups and two treatment groups comprising the 10 mg/kg PS (PS10) and 50 mg/kg PS (PS50) groups. All lung organs were harvested at week 26 for histopathological analysis. Results. All PS treatment groups showed chemopreventive activity by inhibiting the progression of lung SCC formation with PS10, resulting in mild hyperplasia, and PS50 was completely reversed in the normal bronchial epithelium layer compared with the VC group. PS treatment also reduced the expression of cytokeratin 5/6 in the bronchial epithelium layer. Both PS10 and PS50 significantly reduced the epithelium thickness compared to the NTCU group (p<0.05). PS is a potential chemopreventive agent against lung SCC growth by suppressing the progression of pre-malignant lesions and reducing the thickness of the bronchial epithelium. Conclusions. The underlying molecular mechanisms of PS in lung SCC should be further studied
Open Access
Histopathological evaluation of insulin-DMSO formula designed for direct nose-to-brain delivery
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Maher, Mustafa A.; Kandeel, Wafaa A.; Hammam, Olfat A.; Attia, Yasmeen M.; Mahmoud, Soheir; Salah, Mohamed
The combination of insulin and DMSO is a patented (Publication No US8987199B2), noninvasive, pharmaceutically strategized preparation for direct noseto-brain delivery (DN2BD) suggested for the treatment of Alzheimer’s disease (AD). Although its main ingredients have been individually researched, no histopathological investigations have been conducted to address this combination effect on the CNS and nasal tissues in animals. The present work was, therefore, designed to investigate the potential histopathological changes induced by this new pharmaceutical combination using a newly developed refractory staining method. The findings presented herein showed no signs of treatment-related lesions or behavioral changes in Sprague Dawley rats following a three-month successive treatment with two strengths of the formula.