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1.
Pol J Pathol ; 75(1): 54-57, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38741429

RESUMO

A 27-year-old woman with jaundice and abdominal pain was admitted to an emergency ward. The diagnostic process showed that gallstones were causing her symptoms. The patient was treated via endoscopic retrograde cholangiopancreatography (ERCP), and during the procedure she suffered a cardiac arrest. Autopsy findings included multiple pulmonary bile emboli as well as features of disseminated intravascular coagulation. Among 22 thus far described cases of bile pulmonary embolism, 13 were associated with medical procedures involving the liver and biliary tract. We present the case report of a pulmonary bile embolism associated with acute pancreatitis treated via ERCP in a woman with gallbladder bile stones.


Assuntos
Pancreatite , Embolia Pulmonar , Humanos , Feminino , Adulto , Embolia Pulmonar/patologia , Embolia Pulmonar/etiologia , Pancreatite/complicações , Pancreatite/patologia , Evolução Fatal , Doença Aguda , Cálculos Biliares/complicações , Colangiopancreatografia Retrógrada Endoscópica , Bile
2.
Anal Bioanal Chem ; 415(29-30): 7281-7295, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37906289

RESUMO

The lack of specific and sensitive early diagnostic options for pancreatic cancer (PC) results in patients being largely diagnosed with late-stage disease, thus inoperable and burdened with high mortality. Molecular spectroscopic methodologies, such as Raman or infrared spectroscopies, show promise in becoming a leader in screening for early-stage cancer diseases, including PC. However, should such technology be introduced, the identification of differentiating spectral features between various cancer types is required. This would not be possible without the precise extraction of spectra without the contamination by necrosis, inflammation, desmoplasia, or extracellular fluids such as mucous that surround tumor cells. Moreover, an efficient methodology for their interpretation has not been well defined. In this study, we compared different methods of spectral analysis to find the best for investigating the biomolecular composition of PC cells cytoplasm and nuclei separately. Sixteen PC tissue samples of main PC subtypes (ductal adenocarcinoma, intraductal papillary mucinous carcinoma, and ampulla of Vater carcinoma) were collected with Raman hyperspectral mapping, resulting in 191,355 Raman spectra and analyzed with comparative methodologies, specifically, hierarchical cluster analysis, non-negative matrix factorization, T-distributed stochastic neighbor embedding, principal components analysis (PCA), and convolutional neural networks (CNN). As a result, we propose an innovative approach to spectra classification by CNN, combined with PCA for molecular characterization. The CNN-based spectra classification achieved over 98% successful validation rate. Subsequent analyses of spectral features revealed differences among PC subtypes and between the cytoplasm and nuclei of their cells. Our study establishes an optimal methodology for cancer tissue spectral data classification and interpretation that allows precise and cognitive studies of cancer cells and their subcellular components, without mixing the results with cancer-surrounding tissue. As a proof of concept, we describe findings that add to the spectroscopic understanding of PC.


Assuntos
Neoplasias Pancreáticas , Análise Espectral Raman , Humanos , Análise Espectral Raman/métodos , Pâncreas , Núcleo Celular , Neoplasias Pancreáticas
3.
Artigo em Inglês | MEDLINE | ID: mdl-36705799

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) constitutes an independent risk factor for the development of coronary heart disease. Low-grade inflammation has been shown to play an important role in the development of atherosclerosis and NAFLD. Free fatty acid receptor 4 (FFAR4/GPR120), which is involved in damping inflammatory reactions, may represent a promising target for the treatment of inflammatory diseases. Our objective was to evaluate the effect of TUG-891, the synthetic agonist of FFAR4/GPR120, on fatty liver in vivo. METHODS: The effect of TUG-891 on fatty liver was investigated in apoE-/- mice fed a high-fat diet (HFD), using microscopic, biochemical, molecular, and proteomic methods. RESULTS: Treatment with TUG-891 inhibited the progression of liver steatosis in apoE-/- mice, as evidenced by histological analysis, and reduced the accumulation of TG in the liver. This action was associated with a decrease in plasma AST levels. TUG-891 decreased the expression of liver genes and proteins involved in de novo lipogenesis (Srebp-1c, Fasn and Scd1) and decreased the expression of genes related to oxidation and uptake (Acox1, Ehhadh, Cd36, Fabp1). Furthermore, TUG-891 modified the levels of selected factors related to glucose metabolism (decreased Glut2, Pdk4 and Pklr, and increased G6pdx). CONCLUSION: Pharmacological stimulation of FFAR4 may represent a promising lead in the search for drugs that inhibit NAFLD.

4.
Int J Mol Sci ; 23(11)2022 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-35682833

RESUMO

Oxygen balance is crucial for angiogenesis, immunity, and tissue repair. The human oviduct is essential for reproductive function, and any imbalance in homeostasis leads to fertility disturbances and might be a reason for ectopic pregnancy development. Uterine myoma is a widespread benign tumour, which is often accompanied by infertility. Telocytes have been discussed in the contexts of motility, fibrosis development, and angiogenesis. We observed the oviducts from patients with and without uterine myoma, comparing the expression of HIF-1, HO, VEGF and its receptor, NOS, oestrogen, and progesterone receptors by immunolabeling. The myometrial and oviductal telocytes were also compared in both groups. Biochemical analyses were conducted for FSH, LH, AMH, sFlt, oestrogen, and progesterone in blood samples. Patients with uterine myoma have different expressions of sex steroid receptors and an increased number of telocytes. The decreasing VEFG expression was compensated by the rise in the HIF-1 and NOS expression. Blood biochemical analyses revealed a higher progesterone level and lower AMH in patients with uterine myoma. No differences in sFlt, FSH, and LF were observed. Uterine myoma impacts oviduct oxygen homeostasis and might cause fertility disturbances (uterine and oviductal infertility factors).


Assuntos
Infertilidade , Leiomioma , Mioma , Telócitos , Animais , Estrogênios/metabolismo , Feminino , Hormônio Foliculoestimulante/metabolismo , Homeostase , Humanos , Hipóxia/metabolismo , Infertilidade/metabolismo , Leiomioma/metabolismo , Mioma/metabolismo , Mioma/patologia , Oviductos/metabolismo , Oxigênio/metabolismo , Gravidez , Progesterona/metabolismo , Telócitos/patologia
5.
Pathobiology ; 88(1): 78-87, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33254171

RESUMO

This paper presents autopsy findings of 3 COVID-19 patients randomly selected for post-mortem from two tertiary referral Polish hospitals. Analysis of macroscopic, histopathological findings with clinical features was performed. All 3 deceased patients were Caucasian males (average age 61 years, range from 56 to 68 years). Using real-time polymerase chain reaction assay, the patients were confirmed (antemortem) to have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Two patients were obese, and 1 patient had type 2 diabetes mellitus. The medical history of 1 patient included hemorrhagic pancreatitis, gangrenous cholecystitis, Acinetobacter baumanii sepsis, and cholecystectomy. Pulmonary embolism was diagnosed in 2 patients. At autopsy, in 1 case, the lungs showed bilateral interstitial pneumonia with diffuse alveolar damage (DAD), while in another case, interstitial pulmonary lymphoid infiltrates and enlarged atypical pneumocytes were present but without DAD. Microthrombi in lung vessels and capillaries were observed in 2 cases. This study revealed thrombotic complications of COVID-19 and interstitial pneumonia with DAD presence as the main autopsy findings in patients with SARS-CoV-2 infection that was confirmed antemortem with molecular tests. Autopsy studies using tissue sections handled in accordance with SARS-CoV-2 biosafety guidelines are urgently needed, especially in the case of subjects who were below the age of 60.


Assuntos
COVID-19/virologia , Pulmão/virologia , SARS-CoV-2/patogenicidade , Adulto , Idoso , Autopsia/métodos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/virologia , Feminino , Humanos , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real/métodos
6.
Int J Mol Sci ; 22(11)2021 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-34070749

RESUMO

Atherosclerosis and nonalcoholic fatty liver disease are leading causes of morbidity and mortality in the Western countries. The renin-angiotensin system (RAS) with its two main opposing effectors, i.e., angiotensin II (Ang II) and Ang-(1-7), is widely recognized as a major regulator of cardiovascular function and body metabolic processes. Angiotensin-converting enzyme 2 (ACE2) by breaking-down Ang II forms Ang-(1-7) and thus favors Ang-(1-7) actions. Therefore, the aim of our study was to comprehensively evaluate the influence of prolonged treatment with ACE2 activator, diminazene aceturate (DIZE) on the development of atherosclerotic lesions and hepatic steatosis in apoE-/- mice fed a high-fat diet (HFD). We have shown that DIZE stabilized atherosclerotic lesions and attenuated hepatic steatosis in apoE-/- mice fed an HFD. Such effects were associated with decreased total macrophages content and increased α-smooth muscle actin levels in atherosclerotic plaques. Moreover, DIZE changed polarization of macrophages towards increased amount of anti-inflammatory M2 macrophages in the atherosclerotic lesions. Interestingly, the anti-steatotic action of DIZE in the liver was related to the elevated levels of HDL in the plasma, decreased levels of triglycerides, and increased biosynthesis and concentration of taurine in the liver of apoE-/- mice. However, exact molecular mechanisms of both anti-atherosclerotic and anti-steatotic actions of DIZE require further investigations.


Assuntos
Enzima de Conversão de Angiotensina 2/genética , Aterosclerose/tratamento farmacológico , Diminazena/análogos & derivados , Fígado Gorduroso/tratamento farmacológico , Placa Aterosclerótica/tratamento farmacológico , Taurina/biossíntese , Angiotensina I/genética , Angiotensina I/metabolismo , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Aterosclerose/etiologia , Aterosclerose/genética , Aterosclerose/patologia , Dieta Hiperlipídica , Diminazena/farmacologia , Modelos Animais de Doenças , Fígado Gorduroso/etiologia , Fígado Gorduroso/genética , Fígado Gorduroso/patologia , Feminino , Regulação da Expressão Gênica , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Ativação de Macrófagos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/metabolismo , Artérias Mesentéricas/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/metabolismo , Placa Aterosclerótica/etiologia , Placa Aterosclerótica/genética , Placa Aterosclerótica/patologia , Células THP-1 , Taurina/agonistas
7.
Int J Mol Sci ; 22(18)2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34575934

RESUMO

Background: Over the past few years, a better understanding of the biology of G-protein coupled receptors (GPRs) has led to the identification of several receptors as novel targets for free fatty acids (FFAs). FFAR4 has received special attention in the context of chronic inflammatory diseases, including atherosclerosis, obesity and NAFLD, through to its anti-inflammatory effect. Methods: The present study investigates the influence of prolonged treatment with TUG-891-FFAR4 agonist on the development of atherosclerosis plaque in apoE-knockout mice, using morphometric and molecular methods. Results: TUG-891 administration has led to the reduction of atherosclerotic plaque size and necrotic cores in an apoE-knockout mice model. TUG-891-treated mice were administered subcutaneously at a dose of 20 mg/kg three times a week for 4 months. The FFAR4 agonist reduced the content of pro-inflammatory M1-like macrophages content in atherosclerotic plaques, as evidenced by immunohistochemical phenotyping and molecular methods. In atherosclerotic plaque, the population of smooth muscle cells increased as evidenced by α-SMA staining. We observed changes in G-CSF and eotaxin markers in the plasma of mice; changes in the levels of these markers in the blood may be related to macrophage differentiation. Importantly, we observed a significant increase in M2-like macrophage cells in atherosclerotic plaque and peritoneum. Conclusions: Prolonged administration of TUG-891 resulted in significant amelioration of atherogenesis, providing evidence that the strategy based on macrophage phenotype switching toward an M2-like activation state via stimulation of FFAR4 receptor holds promise for a new approach in the prevention or treatment of atherosclerosis.


Assuntos
Compostos de Bifenilo/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Ativação de Macrófagos/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Fenilpropionatos/farmacologia , Receptores Acoplados a Proteínas G/agonistas , Animais , Biomarcadores , Peso Corporal , Plasticidade Celular/efeitos dos fármacos , Imunofenotipagem , Mediadores da Inflamação/sangue , Lipídeos/sangue , Ativação de Macrófagos/genética , Macrófagos/metabolismo , Camundongos , Camundongos Knockout , Camundongos Knockout para ApoE , Fenótipo
8.
Int J Mol Sci ; 22(19)2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34639029

RESUMO

Atherosclerosis and NAFLD are the leading causes of death worldwide. The hallmark of NAFLD is triglyceride accumulation caused by an imbalance between lipogenesis de novo and fatty acid oxidation. Agmatine, an endogenous metabolite of arginine, exerts a protective effect on mitochondria and can modulate fatty acid metabolism. In the present study, we investigate the influence of agmatine on the progression of atherosclerotic lesions and the development of hepatic steatosis in apoE-/- mice fed with a Western high-fat diet, with a particular focus on its effects on the DNL pathway in the liver. We have proved that treatment of agmatine inhibits the progression of atherosclerosis and attenuates hepatic steatosis in apoE-/- mice on a Western diet. Such effects are associated with decreased total macrophage content in atherosclerotic plaque as well as a decrease in the TG levels and the TG/HDL ratio in plasma. Agmatine also reduced TG accumulation in the liver and decreased the expression of hepatic genes and proteins involved in lipogenesis de novo such as SREBP-1c, FASN and SCD1. In conclusion, agmatine may present therapeutic potential for the treatment of atherosclerosis and fatty liver disease. However, an exact understanding of the mechanisms of the advantageous actions of agmatine requires further study.


Assuntos
Agmatina/efeitos adversos , Aterosclerose/etiologia , Aterosclerose/metabolismo , Dieta Ocidental , Fígado Gorduroso/etiologia , Fígado Gorduroso/metabolismo , Lipídeos/sangue , Lipogênese , Animais , Aterosclerose/sangue , Aterosclerose/patologia , Biomarcadores , HDL-Colesterol/sangue , Dieta Ocidental/efeitos adversos , Modelos Animais de Doenças , Suscetibilidade a Doenças , Fígado Gorduroso/sangue , Fígado Gorduroso/patologia , Feminino , Imuno-Histoquímica , Metabolismo dos Lipídeos , Camundongos , Camundongos Knockout para ApoE , Triglicerídeos/sangue
9.
Pol J Pathol ; 71(1): 20-29, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32429651

RESUMO

Prostatic carcinoma (PC) is the most frequent urologic cancer and one of the most frequent cancers in males; it is a heterogeneous disease, in terms of molecular features, morphology and prognosis. About half of cases depends on TMPRSS2-ETS translocation which leads to a production of ERG transcription factor. ERG+ and ERG- cancers seem to differ in a number of features, which could lead to an altered nuclear structure; the aim of the study was to test this hypothesis. The material consisted of total 39 PC cases, representing ERG+ and ERG-, as well as Gleason pattern 3 and 4. Filtering by color deconvolution and automatic segmentation were used, and the properly detected nuclei were manually selected. From each case fifty nuclei were obtained; then geometric features and texture parameters were assessed. The analysis of the collected data showed differences both between ERG+/ERG- and Gleason pattern 3 and 4 cases in most of the features analyzed. Our results suggest that indeed the ERG status, thus likely TMPRSS2-ETS translocation, has an impact on morphology of nuclei in PC, and their differences are evident enough to be detectable by image analysis.


Assuntos
Proteínas de Fusão Oncogênica/genética , Neoplasias da Próstata/diagnóstico , Humanos , Masculino , Gradação de Tumores , Prognóstico , Neoplasias da Próstata/genética , Proteínas Proto-Oncogênicas c-ets/genética , Serina Endopeptidases/genética , Regulador Transcricional ERG/genética , Translocação Genética
10.
Int J Mol Sci ; 20(7)2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30925684

RESUMO

Atherosclerosis and nonalcoholic fatty liver disease (NAFLD) are frequent causes of death in the Western countries. Recently, it has been shown that autophagy dysfunction plays an important role in the pathogenesis of both atherosclerosis and NAFLD; thus, activators of autophagy might be useful for novel therapeutic interventions. Trehalose-a naturally occuring disaccharide present in plants, bacteria, fungi, insects, and certain types of shrimps-is a known inducer of autophagy. However, according to the literature, its anti-atherosclerotic and anti-steatotic potential seem to depend on the experimental setting. The aim of our study was to comprehensively describe the influence of a prolonged treatment with orally administered trehalose on the development of atherosclerotic lesions and hepatic steatosis in apolipoprotein E knockout (apoE-/-) mice in an experimental set up reflecting both moderate and severe proatherogenic conditions: male apoE-/- mice on a chow diet (CD) and female apoE-/- mice fed with a high-fat diet (HFD). We found that exogenous trehalose inhibited atherosclerosis and attenuated hepatic steatosis in apoE-/- mice. Such effects of trehalose were not associated with changes of plasma cholesterol, low-density lipoproteins (LDL), or high-density lipoproteins (HDL). Moreover, the anti-steatotic action of trehalose in the liver was associated with the induction of autophagy. The exact molecular mechanisms of both the anti-atherosclerotic action of trehalose and its inhibitory effect on liver steatosis require further clarification.


Assuntos
Apolipoproteínas E/genética , Aterosclerose/tratamento farmacológico , Autofagia/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Trealose/uso terapêutico , Animais , Aorta/efeitos dos fármacos , Aorta/patologia , Aterosclerose/etiologia , Aterosclerose/genética , Aterosclerose/patologia , Dieta Hiperlipídica/efeitos adversos , Feminino , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/patologia , Trealose/administração & dosagem , Trealose/farmacologia
11.
Clin Exp Pharmacol Physiol ; 45(7): 711-719, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29485188

RESUMO

Endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) plays an important role, not only in endothelium-dependent vasodilation but also in lipid and glucose homeostasis in the liver and exerts beneficial effects on mitochondrial biogenesis and respiration. Thus, the aim of our study was to use iTRAQ-based quantitative proteomics to investigate the changes in protein expression in the mitochondrial and cytosolic fractions isolated from the liver of the double (apolipoprotein E (apoE) and eNOS) knockout (apoE/eNOS-DKO) mice as compared to apoE KO mice (apoE-/- ) - an animal model of atherosclerosis and hepatic steatosis. Collectively, the deficiency of eNOS resulted in increased expression of proteins related to gluconeogenesis, fatty acids and cholesterol biosynthesis as well as the decreased expression of proteins participated in triglyceride breakdown, cholesterol transport, protein transcription & translation and processing in endoplasmic reticulum (ER). Moreover, one of the most downregulated proteins were major urinary proteins (MUPs), which are abundantly expressed in the liver and were shown to be involved in the regulation of lipid and glucose metabolism. The exact functional consequences of the revealed alterations require further investigation.


Assuntos
Apolipoproteínas E/genética , Regulação da Expressão Gênica , Técnicas de Inativação de Genes , Fígado/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Proteínas/metabolismo , Proteômica , Animais , Apolipoproteínas E/deficiência , Feminino , Camundongos , Óxido Nítrico Sintase Tipo III/deficiência
12.
Folia Med Cracov ; 58(3): 89-102, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30521514

RESUMO

INTRODUCTION: Uterine leiomyoma is the most widespread benign tumor affecting women of childbearing age. ere are still gaps in the understanding of its pathogenesiss. Telocytes are unique cells described in greater than 50 different locations inside the human body. The functional relationship of cells could clarify the pathogenesis of leiomyomata. In the current study, we focused on the identification of telocytes in all regions of the human uterus to explain their involvement in leiomyoma development. MATERIALS AND METHODS: Tissue samples from a healthy and myomatous uterus were stained for c-kit, tryptase, CD34 and PDGFRα to identify telocytes. Routine histology was performed to analyze tissue morphology and collagen deposits. RESULTS: Telocytes were detected in the cervix, corpus of the uterus and leiomyoma. The density of telocytes in fibroid foci was reduced compared with normal myometrium. CONCLUSIONS: Our results demonstrated the existence of telocytes in all parts of the human body affected and unaffected by leiomyoma of the uterus. In addition, telocytes were also present in leiomyoma foci. Our results suggest that the reduced density of telocytes is important for the pathomechanisms of myometrial growth, demonstrating its value as a main component of the myomatous architecture.


Assuntos
Colo do Útero/citologia , Leiomioma/patologia , Miométrio/citologia , Telócitos/patologia , Neoplasias Uterinas/patologia , Adulto , Idoso , Antígenos CD34/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Histerectomia , Imuno-Histoquímica , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-kit/metabolismo , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Telócitos/citologia , Telócitos/metabolismo , Triptases/metabolismo
13.
Pol J Pathol ; 67(4): 411-414, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28547971

RESUMO

We present a case of a woman with primary amenorrhea. Ultrasound imaging showed a uterus of normal size but bands of connective tissues at the site of ovaries. A genetic test was done which revealed the XY karyotype. Swyer syndrome was diagnosed. The patient did not report for the follow-up visits. Three years later, the woman reported back because of increasing abdominal circumference. The patient underwent an operation. Radical hysterectomy was performed. Histopathological examination showed dysgerminoma and gonadoblastoma on the left gonad and dysgerminoma on the right one. This case report presents the natural history of Swyer syndrome.


Assuntos
Disgerminoma/patologia , Disgenesia Gonadal 46 XY/complicações , Gonadoblastoma/patologia , Gônadas/patologia , Adolescente , Disgerminoma/genética , Feminino , Gonadoblastoma/genética , Humanos
14.
Pol J Pathol ; 67(3): 244-249, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28155973

RESUMO

A significant proportion of prostatic adenocarcinomas show recurrent translocation leading to ERG expression. Previously we found that ERG+ cases have higher microvessel density than negative ones. One factor influencing angiogenesis in cancer is mast cells. The aim of the present study was to evaluate the relationship between microvessels, mast cells and ERG status. Tissue microarrays prepared from 113 radical prostatectomy specimens were analyzed with immunohistochemistry for CD31, tryptase and chymase. Vascular profiles and tryptase-positive and chymase-positive cells were counted. The average number of tryptase-positive cells was 28.93/mm2 and chymase-positive cells 9.91/mm2. The average number of CD31+ vascular profiles was 352.66/mm2. The average number of tryptase-positive cells was 26.35/mm2 for ERG- cases and 32.12/mm2 for ERG+ cases. The average number of chymase-positive cells was 8.14/mm2 for ERG- cases and 12.06/mm2 for ERG+ cases. The average number of CD31+ vascular profiles was 321.34/mm2 for ERG- cases and 390.74/mm2 for ERG+ cases. The number of CD31+ vascular profiles was positively correlated with the number of tryptase-positive and chymase-positive cells (R = 0.26 and R = 0.20). In summary, we demonstrated an interrelationship between mast cells, microvascular density and ERG status in prostatic carcinoma.


Assuntos
Adenocarcinoma/patologia , Mastócitos/patologia , Neovascularização Patológica/patologia , Neoplasias da Próstata/patologia , Adulto , Idoso , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Análise Serial de Tecidos , Regulador Transcricional ERG/biossíntese
15.
Folia Med Cracov ; 56(1): 81-95, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27513841

RESUMO

Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline) is thought to regulate dopaminergic neurons and to act as a mediator in the neuroendocrine system. We have previously reported that exogenous salsolinol evokes enteric neuronal cell death, leading to the impairment of myenteric neurons density and abnormal intestinal transit in rats. We also observed significant reduction of body weight, related to the disrupted gastrointestinal homeostasis. e aim of current study was to evaluate the influence of prolonged salsolinol administration body weight, food intake, adipose tissue accumulation and fad pad adipocyte morphological parameters assessed by image analysis. Male Wistar rats were subjected to continuous intraperitoneal low dosing of salsolinol - 200 mg/kg in total with ALZET osmotic mini-pumps (Durtec, USA) for 2 or 4 weeks with either normal or high-fat diet. Appropriate groups served as the controls. Food intake, body weight were measured each morning. Both epididymal fat pads were dissected, weighted and processed for routine hematoxylin and eosin staining. e following parameters: cell area, perimeter, long and short axis, aspect ratio and circularity factor were assessed in stained specimens with the image analysis system (Multiscan, Poland). Salsolinol administration significantly reduced total body mass with no differences in total food intake between the groups. The epididymal fat pad weight over final body mass ratio was lower in salsolinol treated rats on high fat diet in comparison with the control groups. e area, perimeter, short and long axis of the fad pad adipocytes were significantly decreased in salsolinol treated animals in comparison with relevant controls. Salsolinol targets some regulatory mechanisms concerned with the basic rat metabolism. Prolonged peripheral salsolinol administration in rats significantly decreases the adipocyte size, and such effect is related to the weight loss and reduced adipose tissue accumulation.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Isoquinolinas/farmacologia , Obesidade/tratamento farmacológico , Adipócitos/efeitos dos fármacos , Animais , Dieta Hiperlipídica , Masculino , Obesidade/prevenção & controle , Ratos , Ratos Wistar
16.
Contemp Oncol (Pozn) ; 20(6): 496-500, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28239290

RESUMO

Ewing's sarcoma (ES) and primitive neuroectodermal tumour (PNET) are now considered to be the same tumour and usually occur in long bones. Extraskeletal Ewing's sarcoma is an extremely rare neoplasm, accounting for 1% of soft tissue sarcomas, with most common location in the thorax. Gallbladder cancer (GBC) represents the most common type among the biliary tract cancers with a poor prognosis even among patients undergoing aggressive therapy. We present study of extraskeletal ES/PNET found in the hilus of the liver of an elderly, diagnosed one month prior with GBC woman. The patient underwent two cycles of chemotherapy SAIME/SAVAC for ES and thereafter was operated. During three-year follow-up no recurrence of ES/PNET has been reported. However, two years after chemotherapy the patient suffered a relapse of adenocarcinoma of the gallbladder and thus received palliative chemotherapy of gemcitabine and cisplatin. After 16 months of recurrence she died. To the best of our knowledge, this is the first case of ES/PNET located in the hilus of the liver and as a synchronous neoplasm.

17.
Mod Pathol ; 28(6): 807-21, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25720320

RESUMO

Despite the established role of SDHB/SDHA immunohistochemistry as a valuable tool to identify patients at risk for familial succinate dehydrogenase-related pheochromocytoma/paraganglioma syndromes, the reproducibility of the assessment methods has not as yet been determined. The aim of this study was to investigate interobserver variability among seven expert endocrine pathologists using a web-based virtual microscopy approach in a large multicenter pheochromocytoma/paraganglioma cohort (n=351): (1) 73 SDH mutated, (2) 105 non-SDH mutated, (3) 128 samples without identified SDH-x mutations, and (4) 45 with incomplete SDH molecular genetic analysis. Substantial agreement among all the reviewers was observed either with a two-tiered classification (SDHB κ=0.7338; SDHA κ=0.6707) or a three-tiered classification approach (SDHB κ=0.6543; SDHA κ=0.7516). Consensus was achieved in 315 cases (89.74%) for SDHB immunohistochemistry and in 348 cases (99.15%) for SDHA immunohistochemistry. Among the concordant cases, 62 of 69 (~90%) SDHB-/C-/D-/AF2-mutated cases displayed SDHB immunonegativity and SDHA immunopositivity, 3 of 4 (75%) with SDHA mutations showed loss of SDHA/SDHB protein expression, whereas 98 of 105 (93%) non-SDH-x-mutated counterparts demonstrated retention of SDHA/SDHB protein expression. Two SDHD-mutated extra-adrenal paragangliomas were scored as SDHB immunopositive, whereas 9 of 128 (7%) tumors without identified SDH-x mutations, 6 of 37 (~16%) VHL-mutated, as well as 1 of 21 (~5%) NF1-mutated tumors were evaluated as SDHB immunonegative. Although 14 out of those 16 SDHB-immunonegative cases were nonmetastatic, an overall significant correlation between SDHB immunonegativity and malignancy was observed (P=0.00019). We conclude that SDHB/SDHA immunohistochemistry is a reliable tool to identify patients with SDH-x mutations with an additional value in the assessment of genetic variants of unknown significance. If SDH molecular genetic analysis fails to detect a mutation in SDHB-immunonegative tumor, SDHC promoter methylation and/or VHL/NF1 testing with the use of targeted next-generation sequencing is advisable.


Assuntos
Neoplasias das Glândulas Suprarrenais/genética , Complexo II de Transporte de Elétrons/análise , Imuno-Histoquímica/normas , Paraganglioma/genética , Feocromocitoma/genética , Succinato Desidrogenase/análise , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Complexo II de Transporte de Elétrons/genética , Humanos , Microscopia/métodos , Mutação , Variações Dependentes do Observador , Succinato Desidrogenase/genética , Telepatologia/métodos
18.
BMC Surg ; 15: 101, 2015 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-26314582

RESUMO

BACKGROUND: Laparoscopic adrenalectomy is still controversial in cases where malignancy is suspected. However, many proponents of this technique argue that in the hands of an experienced surgeon, laparoscopy can be safely performed. The aim of this study is to present our own experience with the application of laparoscopic surgery for the treatment of malignant and potentially malignant adrenal tumours. METHODS: Our analysis included 52 patients who underwent laparoscopic adrenalectomy in 2003-2014 due to a malignant or potentially malignant adrenal tumour. Inclusion criteria were primary adrenal malignancy, adrenal metastasis or pheochromocytoma with a PASS score greater than 6. We analyzed the conversion rate, intra- and postoperative complications, intraoperative blood loss and R0 resection rate. Survival was estimated using the Kaplan-Meier method. RESULTS: Conversion was necessary in 5 (9.7%) cases. Complications occurred in a total of 6 patients (11.5%). R0 resection was achieved in 41 (78.8%) patients and R1 resection in 9 (17.3%) patients. In 2 (3.9%) cases R2 resection was performed. The mean follow-up time was 32.9 months. Survival depended on the type of tumour and was comparable with survival after open adrenalectomy presented in other studies. CONCLUSIONS: We consider that laparoscopic surgery for adrenal malignancy can be an equal alternative to open surgery and in the hand of an experienced surgeon it guarantees the possibility of noninferiority. Additionally, starting a procedure with laparoscopy allows for minimally invasive evaluation of peritoneal cavity. The key element in surgery for any malignancy is not the surgical access itself but the proper technique.


Assuntos
Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia/métodos , Laparoscopia/métodos , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Feocromocitoma/patologia , Feocromocitoma/cirurgia , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento
19.
Pol J Pathol ; 66(4): 397-402, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27003772

RESUMO

Mast cells (MCs) are known to be regulators of inflammation and immunity, due to the released mediators and expressed cell surface molecules. Lupus erythematosus (LE) is a group of diseases which can be systemic or limited to the skin. Due to the fact that cytokines and chemokines produced by inflammatory cells contribute to the pathogenesis of LE, we quantified the number of mast cells present in the skin. The aim of the study was to compare the chymase-positive and tryptase-positive mast cell counts within skin biopsies from patients with systemic lupus erythematosus (SLE), discoid lupus erythematosus (DLE) and subacute cutaneous lupus erythematosus (SCLE). The material consisted of 45 skin biopsies: 6 with SLE, 34 with DLE and 5 with SCLE. Chymase- and tryptase-positive cells were stained by immunohistochemistry and counted. The mean count of chymase-positive mast cells was 85.14 hpf for the whole group, 35.83 for SLE, 88.48 for DLE and 121.6 for SCLE. The mean count of tryptase-positive cells was 120.05 hpf for the entire group, 59.17 for SLE, 126.42 for DLE and 149.8 for SCLE. The differences between groups were significant for chymase- and tryptase-positive cells.


Assuntos
Quimases/metabolismo , Lúpus Eritematoso Discoide/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Mastócitos/enzimologia , Triptases/metabolismo , Adulto , Idoso , Biópsia , Feminino , Humanos , Lúpus Eritematoso Discoide/patologia , Lúpus Eritematoso Sistêmico/patologia , Masculino , Pessoa de Meia-Idade , Pele/patologia , Adulto Jovem
20.
Pol J Pathol ; 66(2): 149-53, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26247528

RESUMO

Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus; in LN class IV morphologic lesions may be similar to the lesions in primary membranoproliferative glomerulonephritis (MPGN). The aim of the study was to compare the counts of tryptase-positive and chymase-positive mast cells between LN class IV and MPGN. The material consisted of 61 renal biopsies: 32 with lupus nephritis class IV, and 29 with membranoproliferative glomerulonephritis. Chymase- and tryptase-positive cells were stained by immunohistochemistry and subsequently counted. The mean count of chymase-positive mast cells was 21.94 for the whole group, 12.66 for LN class IV and 32.18 for MPGN. The mean count of tryptase-positive cells was 34.94 hpf for the entire group, 22.98 for LN class IV and 48. 13 for MPGN. The differences between lupus nephritis and membranoproliferative glomerulonephritis were significant both for chymase- and tryptase-positive cells. Both chymase-positive MC counts and tryptase-positive MC counts correlated with relative interstitial volume (RIV) (R=0.35 and R=0.28, respectively) and with creatinine level (R=0.35 and R=0.43, respectively). There was also a significant correlation between age, creatinine level and RIV (R=0.28 and R=0.26, respectively).


Assuntos
Glomerulonefrite Membranoproliferativa/patologia , Nefrite Lúpica/patologia , Mastócitos/patologia , Adulto , Biomarcadores/análise , Biópsia , Contagem de Células , Quimases/análise , Diagnóstico Diferencial , Feminino , Glomerulonefrite Membranoproliferativa/enzimologia , Humanos , Imuno-Histoquímica , Nefrite Lúpica/enzimologia , Masculino , Mastócitos/enzimologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Triptases/análise , Adulto Jovem
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