International Journal Of Experimental Pathology[JOURNAL]
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200 papers
Death of chondrocytes in Kashin-Beck disease: Apoptosis, necrosis or necroptosis?
Zhang Y, He Y, Zhang D … +5 more , Zhang M, Wang M, Zhang Y, Ma T, Chen J
Int J Exp Pathol · 2018 Dec · PMID 30680829 · Full text
The purpose of this paper was to investigate chondrocyte distribution and death in the cartilage in Kashin-Beck disease (KBD). Apoptotic chondrocytes were detected by TUNEL assay. Ultrastructural changes were examined by...
The purpose of this paper was to investigate chondrocyte distribution and death in the cartilage in Kashin-Beck disease (KBD). Apoptotic chondrocytes were detected by TUNEL assay. Ultrastructural changes were examined by transmission electron microscope (TEM). Biochemical markers associated with apoptosis (eg, caspase-3) and necroptosis (eg, RIP3) were investigated by immunohistochemistry. In KBD cartilage chondrocyte death was characterized by paler staining of the cells. Multiple chondral cell clusters surrounded the areas lacking cells in the deep zone. The per cent of TUNEL-positive and RIP3-positive chondrocytes were higher in the middle zones of KBD samples; however, there was some positive staining for TUNEL but negative staining for caspase-3. Immunohistochemistry failed to detect significant differences in caspase-3 levels in KBD children compared to controls, suggesting that beside apoptosis necroptosis dominates as a cell death mechanism in the middle zone of cartilage from KBD children. To clarify further the presence of chondrocyte necroptosis in KBD, we performed TUNEL, caspase-3 and RIP3 staining in a rat KBD model which is based upon T-2 toxin treatment under selenium-deficient conditions. Apoptosis and necroptosis co-existed in the middle zone in this rat KBD model. Ultrastructural analysis of chondrocyte from deep cartilage revealed abnormal cells with numerous morphological changes, such as plasma membrane breakdown, generalized swelling of the cytoplasm and loss of identifiable organelles. Chondrocyte death by necrosis in the deep zone of cartilages in KBD may be a result of exposure to T-2 toxin from bone marrow or bloodstream under selenium-deficient nutrition status in KBD endemic areas. Chondrocyte death plays a key role in either the initiation or the progression of KBD pathogenesis.
Non-alcoholic steatohepatitis aggravates nitric oxide synthase inhibition-induced arteriosclerosis in SHRSP5/Dmcr rat model.
Watanabe S, Kumazaki S, Yamamoto S … +5 more , Sato I, Kitamori K, Mori M, Yamori Y, Hirohata S
Int J Exp Pathol · 2018 Dec · PMID 30680827 · Full text
Non-alcoholic steatohepatitis (NASH) is linked to increased cardiovascular risk, independent of the broad spectrum of metabolic syndrome risk factors. Stroke-prone (SP) spontaneously hypertensive rats (SHRSP5/Dmcr) fed a...
Non-alcoholic steatohepatitis (NASH) is linked to increased cardiovascular risk, independent of the broad spectrum of metabolic syndrome risk factors. Stroke-prone (SP) spontaneously hypertensive rats (SHRSP5/Dmcr) fed a high-fat and high-cholesterol (HFC) diet developed hepatic lesions similar to those in human NASH pathology. These rats simultaneously developed lipid deposits in the mesenteric arteries, cardiac fibrosis, endothelial dysfunction and left ventricle (LV) diastolic dysfunction. However, the intermediary factors between NASH and cardiovascular disease are still unknown. We investigated whether NASH aggravates nitric oxide (NO) synthase inhibition-induced arteriosclerosis in SHRSP5/Dmcr rats. Wistar Kyoto and SHRSP5/Dmcr rats were divided into 4 groups of 5 and fed the stroke-prone (SP) or HFC diets for 8 weeks. To induce NO synthase inhibition, N -nitro-L-arginine methyl ester hydrochloride (L-NAME) mixed with drinking water was administered in the final 2 weeks. The NASH+L-NAME group demonstrated the following characteristics related to arteriosclerosis and myocardial ischaemia: (a) LV systolic dysfunction with asynergy, (b) replacement fibrosis caused by the shedding of cardiomyocytes and (c) arterial lipid deposition and coronary occlusion secondary to endothelial dysfunction. These characteristics were not observed in the NASH or non-NASH+L-NAME groups. The SHRSP5/Dmcr rat model demonstrates that NASH significantly aggravates cardiovascular risk.
TGFβ1-induced cell motility but not cell proliferation is mediated through Cten in colorectal cancer.
Asiri A, Raposo TP, Alfahed A … +1 more , Ilyas M
Int J Exp Pathol · 2018 Dec · PMID 30648319 · Full text
Cten (C-terminal tensin-like) is a member of the tensin protein family found in complex with integrins at focal adhesions. It promotes epithelial-mesenchymal transition (EMT) and cell motility. The precise mechanisms reg...
Cten (C-terminal tensin-like) is a member of the tensin protein family found in complex with integrins at focal adhesions. It promotes epithelial-mesenchymal transition (EMT) and cell motility. The precise mechanisms regulating Cten are unknown, although we and others have shown that Cten could be under the regulation of several cytokines and growth factors. Since transforming growth factor beta 1 (TGF-β1) regulates integrin function and promotes EMT/cell motility, we were prompted to investigate whether TGF-β1 induces EMT and cell motility through Cten signalling in colorectal cancer. TGF-β1 signalling was modulated by either stimulation with TGF-β1 or knockdown of TGF-β1 in the CRC cell lines SW620 and HCT116. The effect of this modulation on expression of Cten, EMT markers and on cellular function was tested. The role of Cten as a direct mediator of TGF-β1 signalling was investigated in a CRC cell line in which the Cten gene had been deleted (SW620 ). When TGF-β1 was stimulated or inhibited, this resulted in, respectively, upregulation and downregulation of Cten expression and EMT markers (Snail, Rock, N-cadherin, Src). Cell migration and cell invasion were significantly increased following TGF-β1 stimulation and lost by TGF-β1 knockdown. TGF-β1 stimulation of the SW620 cell line resulted in selective loss of the effect of TGF-β1 signalling pathway on EMT and cell motility while the stimulatory effect on cell proliferation was retained. These data suggested Cten may play an essential role in mediating TGF-β1-induced EMT and cell motility and may therefore play a role in metastasis in CRC.
Muscle wasting and branched-chain amino acid, alpha-ketoglutarate, and ATP depletion in a rat model of liver cirrhosis.
Holeček M, Vodeničarovová M
Int J Exp Pathol · 2018 Dec · PMID 30637824 · Full text
The aim of the study was to examine whether a rat model of liver cirrhosis induced by carbon tetrachloride (CCl4) is a suitable model of muscle wasting and alterations in amino acid metabolism in cirrhotic humans. Rats w...
The aim of the study was to examine whether a rat model of liver cirrhosis induced by carbon tetrachloride (CCl4) is a suitable model of muscle wasting and alterations in amino acid metabolism in cirrhotic humans. Rats were treated by intragastric gavage of CCl4 or vehicle for 45 days. Blood plasma and different muscle types-tibialis anterior (mostly white fibres), soleus (red muscle) and extensor digitorum longus (white muscle) - were analysed at the end of the study. Characteristic biomarkers of impaired hepatic function were found in the plasma of cirrhotic animals. The weights and protein contents of all muscles of CCl4-treated animals were lower when compared with controls. Increased concentrations of glutamine (GLN) and aromatic amino acids (phenylalanine and tyrosine) and decreased concentrations of branched-chain amino acids (BCAA), glutamate (GLU), alanine and aspartate were found in plasma and muscles. In the soleus muscle, GLN increased more and GLU and BCAA decreased less than in the extensor digitorum and tibialis muscles. Increased chymotrypsin-like activity (indicating enhanced proteolysis) and decreased α-ketoglutarate and ATP levels were found in muscles of cirrhotic animals. ATP concentration also decreased in blood plasma. It is concluded that a rat model of CCl4-induced cirrhosis is a valid model for the investigation of hepatic cachexia that exhibits alterations in line with a theory of role of ammonia in pathogenesis of BCAA depletion, citric cycle and mitochondria dysfunction, and muscle wasting in cirrhotic subjects. The findings indicate more effective ammonia detoxification to GLN in red than in white muscles.
Establishment of a diabetic myocardial hypertrophy model in Mus musculus castaneus mouse.
Zhang J, Qiu H, Huang J … +4 more , Ding S, Huang B, Wu Q, Jiang Q
Int J Exp Pathol · 2018 Dec · PMID 30614094 · Full text
The aim of this study was to establish a robust model of diabetic myocardial hypertrophy in Mus musculus castaneus mice. Mice were fed a high-fat diet for four weeks and then given streptozotocin (STZ, 40 mg kg d for 5 ...
The aim of this study was to establish a robust model of diabetic myocardial hypertrophy in Mus musculus castaneus mice. Mice were fed a high-fat diet for four weeks and then given streptozotocin (STZ, 40 mg kg d for 5 days, intraperitoneally) and fasting blood glucose (FBG) levels were tested after seven days. Mice with FBG levels above 11.1 mmol/L were considered diabetic. Diabetic mice continued to have access to the high-fat diet until cardiac hypertrophy developed. FBG and body weight (BW) were measured weekly. Myocardial hypertrophy was confirmed by left ventricle (LV) hypertrophy index (LVHI), LV/BW, LV histopathological observation and atrial natriuretic factor (ANF) mRNA expression. Serum insulin and plasma haemoglobin A1c (HbA1c) levels, total cholesterol (TCH) and triglyceride (TG) were measured, and then an insulin resistance index (HOMA.IR) was calculated. The level of FBG in the model group remained above 11.1 mmol/L, and the BW showed significant weight loss, compared with the control group (P < 0.01). The high levels of HbA1c, HOME.IR, TCH and TG, and the low level of insulin suggested that glucose metabolism was not balanced with insulin resistance; meanwhile, higher TCH and TG showed that dyslipidaemia had also developed. After the diabetic mice were kept on the high-energy diet for another four weeks, histopathological observation showed myocardial injuries, much more surface area and collagen fibres, higher LVHI and LV/BW, and elevated expression of ANF mRNA (P < 0.01), suggesting that myocardial hypertrophy had appeared in Mus musculus castaneus mice under the current experimental conditions. Thus a robust model of diabetic myocardial hypertrophy was established four weeks after confirmation of diabetes, which was induced by feeding a high-fat diet for four weeks combined with a repeated low-dose STZ exposure, in Mus musculus castaneus mice.
Histopathological features of skin lesions in patients affected by non-ulcerated or atypical cutaneous leishmaniasis in Honduras, Central America.
Sandoval Pacheco CM, Araujo Flores GV, Favero Ferreira A … +5 more , Sosa Ochoa W, Ribeiro da Matta VL, Zúniga Valeriano C, Pereira Corbett CE, Dalastra Laurenti M
Int J Exp Pathol · 2018 Oct · PMID 30478864 · Full text
In Honduras visceral leishmaniasis and non-ulcerated or atypical cutaneous leishmaniasis (NUCL) are caused by the species Leishmania (L.) infantum chagasi. NUCL is the most common clinical form in the southern regions of...
In Honduras visceral leishmaniasis and non-ulcerated or atypical cutaneous leishmaniasis (NUCL) are caused by the species Leishmania (L.) infantum chagasi. NUCL is the most common clinical form in the southern regions of the country, mainly affecting the young. In view of the lack of knowledge about the pathogenesis of the disease pattern caused by L. (L) infantum chagasi in individuals affected by NUCL, the aim of the present study was to describe in detail the histopathological features of the skin lesion caused by the parasite. Biopsies from human NUCL lesions with a positive parasitological diagnosis were collected and processed using standard histological techniques. Paraffin sections stained by haematoxylin and eosin were used to examine the histopathological alterations seen in the skin. The lesions varied between 3 and 5 mm, and the majority of the patients (60%) had a single lesion. Lesions were more frequently seen in females (65%), with an average age of 33.4 years. Microscopically, the skin lesions were characterized by mononuclear inflammatory infiltrate in the dermis composed of lymphocytes, macrophages and a few plasma cells. The intensity of the infiltration varied from discrete to intense. In both cases, the parasitic infection was discrete. Granulomas were present in 60% of cases and were associated with intense inflammation. The data revealed by the histopathological alterations in the skin of individuals affected by NUCL suggest activation of a cellular immune response that potentially controls parasite spreading.
Nitrogen-containing bisphosphonate therapy-Part II: Assessment of alveolar bone tissue inflammatory response in rats-A blind randomized controlled trial.
Pacheco VN, Langie R, Benfica JRD … +4 more , Munaretto JC, Etges A, Ponzoni D, Puricelli E
Int J Exp Pathol · 2018 Oct · PMID 30457199 · Full text
This study aimed to evaluate the alveolar bone tissue inflammatory response in rats undergoing zoledronic acid therapy. The study sample was composed of 28 Wistar rats. Animals from the test group GTa received a weekly i...
This study aimed to evaluate the alveolar bone tissue inflammatory response in rats undergoing zoledronic acid therapy. The study sample was composed of 28 Wistar rats. Animals from the test group GTa received a weekly intraperitoneal dose of 0.2 mg/kg of zoledronic acid for 3 weeks, while test group GTb received the same dose for 8 weeks. A physiological saline dose, equivalent to that of the medication, was administered to the controls in groups GCa and GCb. A defect was created in the dental crown of the lower first molars using a drill to simulate pulp and periapical injury. Data were evaluated regarding image grey levels by cone-beam computed tomography and histologically by assigning scores for the presence of inflammatory infiltrate, type of infiltrate, vascularization, bone necrosis and dental resorption. Grey levels in the 3-week therapy group (GTa) showed more pronounced changes in comparison with those seen in the GCa group (P < 0.05). Evaluation of the scores demonstrated no association between any of the variables amongst the groups (>0.05). However, bone remodelling decreased in the groups receiving the medication. Bone necrosis was present more frequently in group GTb than in the control group GCb. The results suggest that the drug interfered in the reaction capacity of the alveolar bone tissue as test group GTa showed higher grey levels in comparison to the control group GCa. In addition, there was less bone remodelling activity, with the appearance of bone necrosis zones and intense acute inflammatory infiltrate associated with the 8-week therapy group GTb.
Systemic alterations induced by phospholipase A , BmooTX-I, isolated from Bothrops moojeni snake venom.
Costa KCT, de Sousa BB, Dias EHV … +8 more , Pereira DFDC, Matias MS, Oliveira WJ, Mundim AV, Mamede CCN, Izidoro LFM, Costa JO, de Oliveira F
Int J Exp Pathol · 2018 Oct · PMID 30456925 · Full text
Ophidic accidents are among the problems of public health in Brazil. The components from bothropic venom are responsible for many systemic clinical complications resulting from envenomation. The present work aimed to ana...
Ophidic accidents are among the problems of public health in Brazil. The components from bothropic venom are responsible for many systemic clinical complications resulting from envenomation. The present work aimed to analyse the systemic changes induced in mice after intraperitoneal administration of BmooTX-I, a myotoxic acidic phospholipase A isolated from Bothrops moojeni venom. Urinalysis was performed and the following plasma biochemical markers were documented: urea, creatinine and uric acid (renal function); glucose and amylase (pancreatic function); alanine aminotransferase, alkaline phosphatase and gamma-GT (intra- and extrahepatic function); creatine kinase and enzymatic lactate (muscle function). Our results showed that after the intraperitoneal injection of BmooTX-I the urine of these animals showed glycosuria, proteinuria, haematuria, bacteriuria, bilirubinuria, polyuria and nitrite. The plasma biochemical analysis showed alterations in levels of urea, creatinine and uric acid. Amylase concentration was not altered significantly, but the plasma glucose increased significantly compared to controls. The plasma levels of alanine aminotransferase and alkaline phosphatase decreased and increased, respectively, in these same animals. On the other hand, the plasma γGT concentration did not undergo significant modification compared to the control group. The plasma concentration of CK increased, while the enzymatic lactate concentration decreased after the injection of the BmooTX-I. Therefore, in mice BmooTX-I is capable of causing systemic alterations which manifest as renal, muscular, hepatic and pancreatic impairment.
Omega-6 fatty acids down-regulate matrix metalloproteinase expression in a coronary heart disease-induced rat model.
Lu N, Du Y, Li H … +5 more , Luo Y, Ouyang B, Chen Y, Yang Y, Yang L
Int J Exp Pathol · 2018 Oct · PMID 30443948 · Full text
The present study investigated the therapeutic potential of omega-6 fatty acids, according to their effects on antioxidant markers and matrix metalloproteinases (MMPs), in coronary heart disease-induced rats. Rats were g...
The present study investigated the therapeutic potential of omega-6 fatty acids, according to their effects on antioxidant markers and matrix metalloproteinases (MMPs), in coronary heart disease-induced rats. Rats were grouped into group I (sham control), group II (control), group III (0.5 g/kg bwt of omega-6 fatty acids) and group IV (1 g/kg bwt of omega-6 fatty acids). Reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH), catalase, glutathione peroxidase (Gpx) and acetylcholinesterase (AChE) enzyme activities were determined. ROS and MDA were substantially reduced, whereas SOD, catalase, Gpx and AChE were significantly increased, following supplementation with omega-6 fatty acids. MMP-2 mRNA expression was drastically increased by 95% in group II. Treatment significantly reduced MMP-2 mRNA expression by 12.3% and 26.7% in groups III and IV respectively. MMP-9 mRNA expression drastically increased, by 121%, in group II. Treatment significantly reduced MMP-9 mRNA expression by 22.6% and 29.4% in groups III and IV respectively. MMP-2 protein expression was drastically increased, by 81%, in group II. Treatment significantly reduced MMP-2 protein expression by 9.4% and 26% in groups III and IV respectively. MMP-9 protein expression was drastically increased, by 100%, in group II. Treatment significantly reduced MMP-9 protein expression by 18.9% and 26.9% in groups III and IV respectively. In summary, the consumption of omega-6 fatty acids significantly decreased MDA and ROS, while SOD, catalase, GHS, Gpx and AChE were increased. Furthermore, omega-6 fatty acids significantly downregulated MMP-2 and MMP-9 expression in our coronary heart disease-induced rat model.
Can the indicators of chronic ethanol consumption be minimized by a continuous flaxseed intake?
Latini JTP, Vicente GC, Velarde LGC … +5 more , Benedicto HG, de Castro Resende Â, Teixeira MT, de Almeida KCL, Boaventura GT
Int J Exp Pathol · 2018 Oct · PMID 30338600 · Full text
The aim of this study was to evaluate the use of flaxseed in animals subjected to ethanol-induced hepatotoxicity. Twenty-four male rats were divided into four groups (n = 6): control group (CG) which received a control d...
The aim of this study was to evaluate the use of flaxseed in animals subjected to ethanol-induced hepatotoxicity. Twenty-four male rats were divided into four groups (n = 6): control group (CG) which received a control diet and water ad libitum; flaxseed group (FG) which received control diet with an addition of 25% flaxseed flour and water ad libitum; ethanol control group (ECG) which received control diet and a solution of 10% ethanol (v/v) as the only liquid source; and ethanol flaxseed group (EFG) which received control diet with an addition of 25% flaxseed flour and a solution of 10% ethanol (v/v) as the only liquid source. The animals were euthanized at 60 days, when blood was collected for biochemical analysis and liver was collected for histomorphometric analysis. Rats fed with diets containing flaxseed showed lower values of alkaline phosphatase (P = 0.020) and lower concentration of total bilirubin (P = 0.006), direct bilirubin (P = 0.013) and indirect bilirubin (P = 0.018) compared to ECG and EFG. The groups receiving flaxseed diets demonstrated higher expression of superoxide dismutase (SOD) enzyme (P < 0.001) than CG and ECG but did not affect thiobarbituric acid (TBARS) expression (P = 0.055). Regarding liver analysis, the ECG and EFG showed larger hepatocyte nuclei and paler cytoplasm than the groups who had not received ethanol, and less in fluid accumulation (oedema) in the cytoplasm than was seen in the FG and EFG livers. These latter two groups showed fewer fatty cells than was seen in the groups that had not been given flaxseed, so that the diagnosis of hepatic steatosis was not justified. In conclusion, therefore, this study showed that the indicators of ethanol chronic consumption can be reduced by the introduction of continuous flaxseed dietary intake.
Cellular profile of primary molars with pulp necrosis after treatment with antibiotic paste.
Moura LFAD, Lima MDM, Lima CCB … +4 more , Bandeira AVL, Moura MS, Conde Júnior AM, Rizzo MDS
Int J Exp Pathol · 2018 Oct · PMID 30324690 · Full text
The interradicular region of primary molars is permeated by many foramina, channels and accessories that connect the pulp cavity with the periapical tissues anatomically. Thus, pulp decomposition products or drugs used i...
The interradicular region of primary molars is permeated by many foramina, channels and accessories that connect the pulp cavity with the periapical tissues anatomically. Thus, pulp decomposition products or drugs used in endodontic treatment can trigger inflammatory reactions. The aim of this study was to evaluate the blood cell profile of the alveolar region after extraction of primary molars treated with CTZ paste. Forty-eight primary molars were selected with clinical and radiographic signs of extraction. The sample was divided into three groups with 16 teeth each: Group 1-healthy teeth; Group 2-untreated decayed teeth; and Group 3-teeth treated with CTZ paste. Immediately after the extraction, blood from the interface of the tooth socket was collected and smears were performed for further evaluation. The slides were stained by the Fast Panoptic method and analysed by two previously trained examiners who counted the leucocytes in sets of 100 cells/slide, differentiating them into neutrophils, lymphocytes, monocytes, eosinophils and basophils. The data were analysed statistically by the MANOVA test. The blood samples from Group 2 differed significantly from Group 1 samples for all classes of leucocytes, except basophils, with higher average for lymphocytes (62.56), monocytes (7.81) and eosinophils (2.31). For Group 3, there was a relative difference (P < 0.05) to Group 2, of monocytes and eosinophils values. The blood cellularity interface in the tooth socket of primary teeth treated with CTZ paste is similar to those of healthy, exfoliated teeth and physiologically different from untreated decayed teeth.
Hydroxymethylnitrofurazone treatment in indeterminate form of chronic Chagas disease: Reduced intensity of tissue parasitism and inflammation-A histopathological study.
Scarim CB, de Andrade CR, da Rosa JA … +2 more , Dos Santos JL, Chin CM
Int J Exp Pathol · 2018 Oct · PMID 30320480 · Full text
Hydroxymethylnitrofurazone (NFOH) is a nitrofurazone prodrug effective in vivo during acute infections, and it has less hepatotoxicity effect than the standard drug benznidazole (BZN) which has been used during short- an...
Hydroxymethylnitrofurazone (NFOH) is a nitrofurazone prodrug effective in vivo during acute infections, and it has less hepatotoxicity effect than the standard drug benznidazole (BZN) which has been used during short- and long-term treatment. In the present study, we induced the indeterminate form of Chagas disease in mice with a Y strain of Trypanosoma cruzi and analysed the histopathological data about the effects of NFOH and BZN on different tissues, including the heart, skeletal muscle, liver, kidney, colon, spleen and brain. After infection, BALB/c mice were treated with NFOH (150 mg/kg) and BZN (60 mg/kg) for 60 days and then submitted to immunosuppression using dexamethasone (5 mg/kg) for 14 days. Two trained analysts, as part of a blind evaluation, examined the results using serial sections of 3 mm diameter in two different moments. The results showed reactivation of the disease only in the infected nontreated group (POS). After treatment, amastigote nests were found in the heart, colon, liver and skeletal muscle in the POS group and in the heart and liver of the BZN group. Interestingly, amastigote nests were not found in the NFOH and NEG groups. The histopathological analysis showed fewer tissue lesions and parasite infiltrates in the NFOH group when compared with the BZN and POS groups. We have not observed any increase in the levels of hepatocellular injury biomarkers (AST/ALT) in the NFOH group. These in vivo studies show the potential for NFOH as an effective and safe compound useful as an anti-T. cruzi agent.
Histopathological changes in androgenized ovaries are recovered by melatonin treatment.
de Souza BR, de Almeida Chuffa LG, Simão VA … +1 more , Camargo ICC
Int J Exp Pathol · 2018 Aug · PMID 30256483 · Full text
Nandrolone decanoate (ND) is a synthetic steroid, which promotes adverse effects on the ovarian tissue, and melatonin (MLT) exhibits a number of beneficial properties in the reproductive system. This study evaluated the...
Nandrolone decanoate (ND) is a synthetic steroid, which promotes adverse effects on the ovarian tissue, and melatonin (MLT) exhibits a number of beneficial properties in the reproductive system. This study evaluated the general features of the ovarian tissue and the immunoexpression of sex steroid receptors in ND-treated rats that were submitted to short-term melatonin treatment. Adult rats received mineral oil (control group) and ND at doses of 7.5 mg/kg for 15 days (ND-treated group). The treatment with MLT (10mg/kg for 7 days) was given alone, before or in combination with ND. All ND-treated animals showed persistent dioestrus. In the androgenized groups that received MLT, ovarian morphology and size, and the number/area of corpora lutea were recovered. The number of healthy and atretic follicles was recovered when MLT was administered prior to ND; this was similar to the ovaries of control and MLT groups. There was a decrease in estrogen receptors immunostaining in the follicles of androgenized rats that were treated with MLT, and pretreatment with MLT reduced the expression of androgen receptor in atretic follicles and corpora lutea, when compared with ND-treated group. We conclude that MLT treatment recovered the histopathological aspects of the androgenized ovaries, and MLT pretreatment was the most effective.
Hyperactivation of the hypothalamo-pituitary-adrenocortical axis in streptozotocin-diabetic gerbils (Gerbillus gerbillus).
Hammadi S, Chan O, Abdellali M … +5 more , Medjerab M, Agoun H, Bellahreche Z, Khalkhal A, Dahmani Y
Int J Exp Pathol · 2018 Aug · PMID 30256482 · Full text
This study was designed to investigate the HPA-axis impairment in the streptozotocin (STZ)-diabetic gerbils (Gerbillus gerbillus). Twenty-six male gerbils (body weight ~27 g) were divided into 3 groups: vehicle control (...
This study was designed to investigate the HPA-axis impairment in the streptozotocin (STZ)-diabetic gerbils (Gerbillus gerbillus). Twenty-six male gerbils (body weight ~27 g) were divided into 3 groups: vehicle control (n = 10), 2 days of diabetes (n = 09) and 30 days of diabetes (n = 07). The latter 2 groups received an intraperitoneal injection of STZ (150 mg/kg of body weight). At 2 and 30 days of diabetes, streptozotocin-diabetic gerbils underwent a retro-orbital puncture for assessment of biochemical and hormonal parameters. Subsequently the animals were decapitated and the adrenal glands were removed, weighed and processed for light microscopy and stereology. Nondiabetic control gerbils that had been injected with citrate buffer were examined as a comparison. At 2 days of diabetes, STZ gerbils exhibited symptoms that are characteristic of human diabetes type 1. The adrenal gland showed significant increase in weight, associated with a larger cortex layer, hypertrophy of the fasciculate cells and a significant decrease in the nucleocytoplasmic index. These changes were associated with higher plasma ACTH and cortisol concentrations compared to nondiabetic controls. At 30 days postdiabetes, ACTH levels remained elevated, whereas cortisol levels decreased compared to the early stage of diabetes. Histological analysis revealed the existence of a band of connective tissue (collagen) that separates the cortical and medullary zones and is not present in humans or laboratory rodents, which represents a striking change seen throughout the disease. STZ-induced diabetes mellitus in Gerbillus gerbillus resulted in hyperactivation of the HPA axis in the early stages of diabetes mellitus which did not persist into the final stages of the disease, suggesting a possible reduction in adrenocortical sensitivity over time.
Adaptive growth changes in the liver remnant are affected by the size of hepatectomy in rats.
Meier M, Andersen KJ, Knudsen AR … +3 more , Nyengaard JR, Hamilton-Dutoit S, Mortensen FV
Int J Exp Pathol · 2018 Aug · PMID 30198172 · Full text
In this study we investigated the dynamics of hepatocyte hyperplasia and hypertrophy in rats subjected to increasing sizes of partial hepatectomy (PH). A total of 104 rats were randomized according to the size of PH. On...
In this study we investigated the dynamics of hepatocyte hyperplasia and hypertrophy in rats subjected to increasing sizes of partial hepatectomy (PH). A total of 104 rats were randomized according to the size of PH. On postoperative days (PODs) 1, 3 and 5, blood was drawn and the remnant liver removed for stereological analysis. Liver parameters and regeneration rate were significantly affected by size of PH. On POD 1, hepatocyte volumes had increased significantly in all PH groups. On POD 3, all groups showed hepatocyte volumes approximating baseline. On POD 5, hepatocyte volumes were significantly lower in PH (90) than in baseline, sham and PH (30) rats. Increasing hepatocyte proliferation was not observed following PH (30). Following PH (70), cell proliferation was significantly elevated on PODs 1 and 3, and following PH (90) on PODs 3 and 5. In conclusion, general hypertrophy of hepatocytes after different size of PH was followed by hepatocyte proliferation only in the liver remnant of PH (70) and PH (90).
Neuroprotective effect of carnosine in the olfactory bulb after vanadium inhalation in a mouse model.
Colín-Barenque L, Bizarro-Nevares P, González Villalva A … +6 more , Pedraza-Chaverri J, Medina-Campos ON, Jimenez-Martínez R, Rodríguez-Rangel DS, Reséndiz S, Fortoul TI
Int J Exp Pathol · 2018 Aug · PMID 30198103 · Full text
Carnosine (β-alanyl-L-histidine) is synthesized in the olfactory system, has antioxidant activity as a scavenger of free radicals and has been reported to have neuroprotective action in diseases which have been attribute...
Carnosine (β-alanyl-L-histidine) is synthesized in the olfactory system, has antioxidant activity as a scavenger of free radicals and has been reported to have neuroprotective action in diseases which have been attributed to oxidative damage. In neurodegenerative disorders, such as Parkinson's and Alzheimer's diseases, impairment of olfactory function has been described. Vanadium derivatives are environmental pollutants, and its toxicity has been associated with oxidative stress. Vanadium toxicity on the olfactory bulb was reported previously. This study investigates the neuroprotective effect of carnosine on the olfactory bulb in a mice model of vanadium inhalation. Male mice were divided into four groups: vanadium pentoxide (V O ) [0.02 mol/L] inhalation for one hour twice a week; V O inhalation plus 1 mg/kg of carnosine administered daily; carnosine only, and the control group that inhaled saline. The olfactory function was evaluated using the odorant test. Animals were sacrificed four weeks after exposure. The olfactory bulbs were dissected and processed using the rapid Golgi method; cytological and ultrastructural analysis was performed and malondialdehyde (MDA) concentrations were measured. The results showed evidence of olfactory dysfunction caused by vanadium exposure and also an increase in MDA levels, loss of dendritic spines and necrotic neuronal death in the granule cells. But, in contrast, vanadium-exposed mice treated with carnosine showed an increase in dendritic spines and a decrease in neuronal death and in MDA levels when compared with the group exposed to vanadium without carnosine. These results suggest that dendritic spine loss and ultrastructural alterations in the granule cells induced by vanadium are mediated by oxidative stress and that carnosine may modulate the neurotoxic vanadium action, improving the olfactory function.
A histomorphometric classification system for normal and inflamed mouse duodenum-Quali-quantitative approach.
Pereira E Silva A, Soares JRA, Mattos EBA … +4 more , Josetti C, Guimarães IM, Campos SMN, Teixeira GAPB
Int J Exp Pathol · 2018 Aug · PMID 30175413 · Full text
Gut-associated intestinal lymphoid tissue, the largest secondary lymphoid organ in the human body, constantly samples antigens from the gut lumen, presenting as a default response the activation of TCD4 FOXP3 regulatory...
Gut-associated intestinal lymphoid tissue, the largest secondary lymphoid organ in the human body, constantly samples antigens from the gut lumen, presenting as a default response the activation of TCD4 FOXP3 regulatory T cells that secrete a profile of anti-inflammatory cytokines maintaining gut homeostasis denominated from an immunological perspective as mucosal tolerance. However, when antigens are sampled in an inflammatory setting, the immune response may either be protective, in the case of harmful pathogens, or cause further inflammatory reactions as in food allergy, inflammatory bowel diseases, coeliac disease or food protein-induced enterocolitis syndrome. Therefore, there is a need for accurate and consistent experimental models. However, a drawback in comparing these models is the lack of a classification system similar to that which is already used for humans. Thus, the aim of this work was to propose a classification system of the small intestinal histomorphology in experimental mice. To do this we used a mouse antigen-specific gut inflammation model developed by our research group. Duodenum sections stained with haematoxylin-eosin and Alcian blue were scanned using the APERIO scanning system and analysed with the ImageScope software. The evaluated parameters were villus area, villus height and width, enterocyte count, mononuclear intra-epithelial leucocyte and goblet cell counts, and architectural and cellular ratios. Food-sensitized animals challenged with a diet containing the corresponding food allergen presented, as for humans, time-dependent shortened and widened villi accompanied by leucocyte infiltrate and loss of goblet cells. With these data, we were able to establish a classification system for experimental intestinal inflammation in mice thus permitting better comparisons among and between experiments than has been possible previously.
Association of miR-1247-5p expression with clinicopathological parameters and prognosis in breast cancer.
Zhang P, Fan C, Du J … +2 more , Mo X, Zhao Q
Int J Exp Pathol · 2018 Aug · PMID 30175411 · Full text
Our study aimed to clarify the correlation between miR-1247-5p expression and clinicopathological parameters and survival of patients with breast cancer (BC). We evaluated the expression level of miR-1247-5p in 224 forma...
Our study aimed to clarify the correlation between miR-1247-5p expression and clinicopathological parameters and survival of patients with breast cancer (BC). We evaluated the expression level of miR-1247-5p in 224 formalin-fixed, paraffin-embedded specimens (112 BC and matched cancer free tissues) by quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR). miR-1247-5p expression in BC tissues was found to be decreased compared with matched normal tissues (P < 0.01). Additionally, low miR-1247-5p expression in BC tissues was significantly associated with the advanced TNM stage (P = 0.007), lymph node metastasis (P = 0.015), poorer pathological differentiation (P = 0.005) and molecular subtype (P = 0.027). The patients in the low miR-1247-5p group had a shorter disease-free survival and overall survival than those in the high miR-1247-5p group (P < 0.01). Furthermore, the univariate and the multivariate analyses showed that miR-1247-5p expression was an independent predictor of overall survival (P < 0.01). Our study showed that miR-1247-5p was related to the biological behaviour of breast tumour and prognosis of patients with BC. miR-1247-5p could be a novel tumour suppressor and act as a potential biomarker and therapeutic agent for breast carcinoma.
Corrigendum.
Int J Exp Pathol · 2018 Jun · PMID 30133064 · Full text
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Transforming growth factor-β1 (TGF-β1) induces mouse precartilaginous stem cell differentiation through TGFRII-CK1ε-β-catenin signalling.
Qiong W, Xiaofeng G, Junfang W
Int J Exp Pathol · 2018 Jun · PMID 30073722 · Full text
Precartilaginous stem cells (PSCs) are adult stem cells which could self-renew or differentiate into chondrocytes to promote bone growth. In this study, we aimed to understand the role of transforming growth factor-β1 (T...
Precartilaginous stem cells (PSCs) are adult stem cells which could self-renew or differentiate into chondrocytes to promote bone growth. In this study, we aimed to understand the role of transforming growth factor-β1 (TGF-β1) in precartilaginous stem cell (PSC) differentiation and to study the mechanisms that underlie this role. We purified PSCs from the neonatal murine perichondrial mesenchyme using immunomagnetic beads, and primary cultured them. Their phenotype was confirmed by the PSC marker fibroblast growth factor receptor-3 (FGFR-3) overexpression. TGF-β1 was added to induce PSCs differentiation. TGF-β1 increased mRNA expression of chondrogenesis-related genes (collagen type II, Sox 9 and aggrecan) in the cultured PSCs. This was abolished by TGF-β receptor II (TGFRII) and Casein kinase 1 epsilon (CK1ε) lentiviral shRNA depletion. Meanwhile, we found that TGF-β1 induced CK1ε activation, glycogen synthase kinase-3β (GSK3β) phosphorylation and β-catenin nuclear translocation in the mouse PSCs, which was almost completely blocked by TGFRII and CK1ε shRNA knockdown. Based on these results, we suggest that TGF-β1 induces CK1ε activation to promote β-catenin nuclear accumulation, which then regulates chondrogenesis-related gene transcription to eventually promote mouse PSC differentiation.
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