Immunohistochemical assessment of mitochondrial superoxide dismutase (MnSOD) in colorectal premalignant and malignant lesions

Introduction: It is generally accepted that mitochondria are a primary source of intracellular reactive oxygen species (ROS). Under physiological circumstances they are permanently formed as by-products of aerobic metabolism in the mitochondria. To counter the harmful effect of ROS, cells possess an antioxidant defence system to detoxify ROS and avert them from accumulation at high concentrations. Mitochondria-located manganese superoxide dismutase (MnSOD, SOD2) successfully converts superoxide to the less reactive hydrogen peroxide (H2O2). To the best of our knowledge, there are no available data regarding immunohistochemical expression of MnSOD in colorectal neoplastic tissues. Aim: To investigate the immunohistochemical expression status of MnSOD in colorectal premalignant and malignant lesions. Material and methods: This study was performed on resected specimens obtained from 126 patients who had undergone surgical resection for primary sporadic colorectal cancer, and from 114 patients who had undergone colonoscopy at the Municipal Hospital in Jaworzno (Poland). Paraffin-embedded, 4-mu m-thick tissue sections were stained for rabbit polyclonal anti SOD2 antibody obtained from GeneTex (clone TF9-10-H10 from America Diagnostica). Results: Results of our study demonstrated that the development of colorectal cancer is connected with increased expression of MnSOD both in adenoma and adenocarcinoma stages. Samples of adenocarcinoma with G(2) and G(3) grade showed significantly higher levels of immunohistochemical expression of this antioxidant enzyme. Moreover, patients with the presence of lymphovascular invasion and higher degree of regional lymph node status have been also characterised by higher levels of MnSOD expression. The samples of adenoma have been characterised by higher levels of MnSOD expression in comparison to normal mucosa as well. Interestingly, there was no significant correlation between expression and histological type of adenoma. Conclusions: Development of colorectal cancer is connected with increased expression of MnSOD both in adenoma and adenocarcinoma stages. Keyword

Decreased immunoreactivity of von Willebrand factor may reflect persistent nature of the endothelial dysfunction in non-ischemic heart failure

Introduction. Endothelial dysfunction is a critical part of heart failure (HF) pathophysiology. It is not clear, however, whether it is present at the similar level in the early and late HF stages. Material and methods. von Willebrand factor (vWF) and its mRNA levels in biopsies of non-ischemic patients with HF secondary to dilated cardiomyopathy were studied. Consecutive patients with HF were divided into two groups: group A with disease duration ≤ 12 months (n = 59) and group B with disease duration > 12 months (n = 68). The immunoreactivity of the vWF was compared with autopsy sections of 19 control cases. Tissue vWF gene expression was analyzed at the mRNA level by RT-PCR. Results. In the group A, there was lower vWF immunoreactivity in the coronary microvessels compared to the group B [1.5 (1.0–2.0) vs. 2.0 (1.5–2.4), P = 0.001]. In the control group, only weak vWF expression was observed. Protein expression was not accompanied by vWF mRNA whose levels were significantly higher in the Group A as compared to the Group B [14671 (4932-51561) vs. 3643 (185.3–9030.8), P = 0.005]. Protein vWF expression was inversely associated with its mRNA levels (r = –0.34, P = 0.04). Conclusions. High myocardial protein expression of vWF in patients with long-lasting HF symptoms mayhighlight the persistent nature of endothelial dysfunction in such a cohort of patients

The Clinical Application of Immunohistochemical Expression of Notch4 Protein in Patients with Colon Adenocarcinoma

The Notch signalling pathway is one of the most conserved and well-characterised pathways involved in cell fate decisions and the development of many diseases, including cancer. Among them, it is worth noting the Notch4 receptor and its clinical application, which may have prognostic value in patients with colon adenocarcinoma. The study was performed on 129 colon adenocarcinomas. Immunohistochemical and fluorescence expression of Notch4 was performed using the Notch4 antibody. The associations between the IHC expression of Notch4 and clinical parameters were analysed using the Chi2 test or Chi2Yatesa test. The Kaplan–Meier analysis and the log-rank test were used to verify the relationship between the intensity of Notch4 expression and the 5-year survival rate of patients. Intracellular localisation of Notch4 was detected by the use of the immunogold labelling method and TEM. 101 (78.29%) samples had strong Notch4 protein expression, and 28 (21.71%) samples were characterised by low expression. The high expression of Notch4 was clearly correlated with the histological grade of the tumour (p p p p p < 0.001)

Expression of TRAIL and Fas in Primary Hyperparathyroidism

Aim: Differentiating between parathyroid lesions is still difficult and ambiguous. In cases of primary hyperparathyroidism, appropriate and prompt diagnosis is of great importance for effective treatment and follow-up. A great amount of mechanisms contribute to the pathogenesis of primary hyperparathyroidism, such as disturbance in balance between pro- and anti-apoptotic factors. Therefore, we examined whether immunohistochemical expression of apoptotic factors, TNF-related apoptosis-inducing ligand (TRAIL) and Fas, could have clinical utility as a marker of proliferative lesions of parathyroid gland. Materials and methods: Parathyroid specimens of 58 consecutive patients who had undertaken surgery due to primary hyperparathyroidism were incubated with purified mouse monoclonal antihuman antibodies: anti-TRAIL and anti-Fas. Staining was considered positive when at least 5% of the cells showed immunoreactivity. Results: The percentage of cells which were positively stained for TRAIL in parathyroid hyperplasia was 9.65%, in parathyroid adenoma 8.31%, and in normal controls 2.24%. Immunoreactivity for TRAIL was detected in 91.89% of parathyroid hyperplasias, 85.71% of parathyroid adenomas, and none in healthy glands. The percentage of cells with a positive reaction to Fas in parathyroid hyperplasia was 8.92%, in parathyroid adenoma 8.09%, and in normal tissue 1.9%. The expression of Fas was found in 94.59% of parathyroid hyperplasias, 90.48% of parathyroid adenomas, and none in healthy glands. Conclusions: In our study, hyperplasias demonstrated the highest expression of TRAIL and Fas, whereas in adenomas it was increased compared to normal tissue, but lower than in hyperplasias. These factors could be an additive tool in the differential diagnosis of parathyroid lesions

Changes in the legal system in the field of security against the background of the 2015 migration crisis

Niniejsza praca koncentruje się na prawnych aspektach kryzysu migracyjnego. Aby zrozumieć specyfikę zagadnienia, należy pamiętać, że migranci przesiedlają się nie tylko w celu poprawy sytuacji życiowej czy z powodu braku poczucia bezpieczeństwa w swym państwie. Przyczyny migracji to zagadnienie wielopłaszczyznowe. Osoby decydujące się na ucieczkę z własnego kraju często ryzykują utratę życia, chcąc wyrwać się spod politycznego ucisku, w którym nie są w stanie żyć w zgodzie z własnymi przekonaniami. Emigranci opuszczają ojczyznę również z powodów ekonomicznych, chcąc poprawić byt materialny bądź widząc perspektywę samorozwoju. Wędrówki te można podzielić na dokonywane zgodnie z obowiązującymi normami prawa, określonymi dla danego regionu, często reprezentowanego przez podmiot międzynarodowy, jak np. Unia Europejska, czy normami krajowymi oraz na takie, które są dokonywane wbrew przepisom prawa, a więc nielegalnie. Pamiętać należy, że za każdym imigrant stoi osobna, często bardzo złożona i dramatyczna historia. Dla zabezpieczenia podstawowych praw człowieka, w ramach Organizacji Narodów Zjednoczonych 10 grudnia 1948 roku została przyjęta Powszechna deklaracja praw człowieka, która gwarantuje każdemu prawo do swobodnego poruszania się i wyboru miejsca zamieszkania w granicach każdego państwa oraz prawo do posiadania obywatelstwa. W dobie zmian społecznych, globalizacji, rewolucji cyfrowej i kilku kryzysów migracyjnych ostatnich lat, w ramach ONZ 19 grudnia 2018 roku powstał Światowy Pakt ws. Migracji, który zawiera szereg zasad służących zwiększeniu bezpieczeństwa. Kryzys migracyjny, nazywany również uchodźczym, który swoje apogeum miał w 2015 roku, uznany został za największe tego typu zjawisko po II wojnie światowej i wstrząsnął opinią publiczną na całym świecie. Odpowiedzią organów Unii Europejskiej na ten problem był 10-punktowy plan natychmiastowych działań. Szacuje się, że do Europy emigrowało w tym czasie około 2 milionów osób, a na szlakach lądowych i morskich życie straciło co najmniej 20 tysięcy migrantów. W celu zagwarantowania bezpieczeństwa granic Unii oraz wsparcia dla osób potrzebujących pomocy humanitarnej podjęto szereg działań, takich jak stworzenie planu relokacji osób ubiegających się o azyl w Europie wśród już przebywających na kontynencie oraz zorganizowanie powrotu osób, które nie spełniały warunków azylowych.This paper discusses the legal issues in the field of migration crisis that the European community has been dealing with in recent years. To understand the specifics of this issue, it should be realized that people from time immemorial have moved from place to place in order to improve their living conditions. Migrants are resettling to improve their lives, lacking security in a country that cannot or does not want to guarantee it. Reasons for migration can be as plentiful and varied as are migrants themselves. Refugees decide to escape their own country, risk their own and their families’ lives, yearning to break free from oppression that prevents them from observing their faith, following passions, or expressing their views. Emigrants decide to leave their homeland for economic reasons, to improve their financial situation, or achieve self-actualization. Their journeys split between those made in accordance with applicable national and international legal norms, such as ones dictated by the European Union, and those that are carried out against the law. It is important to remember that each immigrant represents a unique, often overly complex story, one of the myriad human dramas that we have faced since our civilization has begun. To safeguard a set of basic human rights, the Universal Declaration of Human Rights of December 10, 1948 was adopted by the United Nations, guaranteeing to all persons the right to unimpeded movement, choice of where to live within each country, and to their nationality. Compelled by social change, globalization, digital revolution and several migratory crises of recent years, the Global Compact for Migration of December 19, 2018 was developed by the UN, containing several principles designed to make migration safer. Poland has not yet acceded to the agreement. The migration crisis, also known as the refugee crisis, that has started in 2015, was recognized as the largest of its kind since the Second World War, overtaking the public discourse around the world. The European Union responded to it with a 10-point plan of immediate actions. It is estimated that as many as two million people immigrated to Europe during that time. At least 20,000 people lost their lives in transit via sea and land. In order to guarantee the security of the Union's borders and to significantly increase support for people in need of humanitarian assistance, a number of actions have been taken, such as creating plans to relocate asylum seekers that are already in Europe and to allow for the return of those who had not met asylum conditions. To date, the European Union has fundamentally increased the security of its borders, combats the smuggling of illegal immigrants and offers secure ways to enter its territory legally. The EU-Turkey agreement was crucial in helping to resolve this problem, by providing Greece the ability to send refugees who had not received asylum in a member state of the European Union to Turkey

Apoptosis in Primary Hyperparathyroidism

Primary hyperparathyroidism (PHPT) is defined by inappropriate elevation of parathormone, caused by parathyroid hyperplasia, also known as multi-gland disease (MGD), parathyroid adenoma (PA), or parathyroid carcinoma (PC). Although several studies have already been conducted, there is a lack of a definite diagnostic marker, which could unambiguously distinguish MGD from PA or PC. The accurate and prompt diagnosis has the key meaning for effective treatment and follow-up. This review paper presents the role of apoptosis in PHPT. The comparison of the expression of Fas, TRAIL, BCL-2 family members, p53 in MGD, PA, and PC, among others, was described. The expression of described factors varies among proliferative lesions of parathyroid gland; therefore, these could serve as additional markers to assist in the diagnosis