Protective Role of S-Adenosylmethionine Against Fructose-Induced Oxidative Damage in Obesity

Introduction. It has been shown that S-adenosylmethionine (S-AMe) stimulates glutathione synthesis and increases cell resistance to the cytotoxic action of free radicals and pro-inflammatory cytokines. The aim of this study was to determine the effect of S-adenosylmethionine on the oxidative stress in adipose tissue in a model of fructose-induced obesity. Methods. The study was performed on male Wistar rats divided into 3 groups: control, fructose fed (HFD) (35%, 16 weeks), and HFD + S-AMe (20 mg/kg). We examined the changes in the ratio of retroperitoneal adipose tissue weight / body weight; levels of reduced glutathione (GSH) and malondialdehyde (MDA) in the retroperitoneal adipose tissue, and serum levels of GSH and TNF-α. Results. Significant increases in the retroperitoneal adipose tissue, MDA, and serum TNF-α were identified, as well as decreased tissue and serum levels of GSH in rats fed with a high-fructose diet as compared with the control group. In the group fed with HFD and S-AMe, we found significant reduction in the retroperitoneal adipose tissue and decreased levels of MDA and serum TNF-α, as well as increased tissue and serum levels of GSH as compared with the group only on HFD. In conclusion, our results show that fructose-induced obesity causes oxidative stress in hypertrophic visceral adipose tissue. The administration of S-AMe improves the antioxidative protection of adipocytes, and reduces oxidative damage and excessive accumulation of lipids and inflammation

Agroecological conditions for growing some hybrids of sunflower in Ovche Pole region

Sunflower is a very important agricultural crop in the Republic of Macedonia and in other countries around the world. It is a high-yielding oilseed industrial culture, and it is characterized by high fatness that ranges up to 50% of the total weight of the seed in newer hybrids. This study used the latest hybrids that are grown in Macedonia without irrigational conditions in the Ovce pole region (dry and warm region). These characteristics in the production of sunflower were a challenge to set up and examine 12 varieties of hybrids in the Ovce pole region in the period from 2016 to 2017, from the sowing stage (April 2016/17) up to the phase of the sunflower harvest (Sept. 2016/17)

Radiotherapy and cell death. Significance of cell death patterns in the radiotherapy of cancer patients

Лъчелечението е един от трите основни метода за лечение на онкологичните заболявания заедно с хирургията и химиотерапията. Прилага се при 50-60% от всички онкоболни на определен етап от тяхното комплексно лечение, като при повече от половината пациенти лъчелечението се прилага с радикална цел. Основна цел е реализиране на максимална доза в тумора и минимална доза в околните здрави тъкани. Развитието на съвременните техники на лъчелечение - 3Д конформално лъчелечение, модулирано по интензитет лъчелечение, образно ръководено лъчелечение - водят до значителен напредък в терапевтичните резултати. Въпреки това остава неизяснен въпросът защо някои тумори са чувствителни, a други са резистентни към приложеното лечение. Основна мишена на йонизиращото лъчение е ДНК. Чрез директното си и индиректно действие йонизиращите лъчения предизвикват структурни промени в ДНК и клетъчна смърт. Клетъчната смърт се приравнява на всеки процес, който води до загуба на митотична активност. Механизмът на лъчево индуцираната клетъчна смърт все още не е напълно изяснен. Съществуват много проучвания, които разкриват редица сигнални пътища и тяхната роля в индуцирането на лъчева резистентност и съответно чувствителност. Разкриването на точните механизми на клетъчна смърт ще да- дат възможност за откриването на нови таргетни терапии, a съчетаването им с лъчелечение ще подобри лечебните резултати.Radiotherapy is one of the three main treatment modalities of cancer, together with surgery and chemotherapy. It is applied to 50% - 60% of all cancer patients at a certain stage of their complex treatment, and in more than half of the patients radiotherapy is used with radical intent. The main goal is to deliver a high dose of radiation to the tumor, while maintaining an acceptable dose to adjacent tissues. The development of modern radiotherapy techniques - 3D conformal radiotherapy, intensity-modulated radiotherapy (IMRT), image-guided radiation therapy (IGRT), leads to significant advances in the therapeutic results. Nevertheless it is still not clear why some tumors are sensitive and others are resistant to irradiation. The main target of ionizing radiation is DNA. By direct and indirect action, ionizing radiation induces structural changes in DNA and cell death. Cell death is equivalent to any process that leads to loss of mitotic activity. The mechanism of radiation-induced cell death has not been fully understood yet. There are many studies that reveal a number of signaling pathways and their role in inducing radiation resistance and sensitivity, respectively. Finding the exact mechanisms of cell death will allow us to discover new target therapies, and combining them with radiotherapy will improve therapeutic results

2-year single center clinical experience in patients with colon cancer stage II and III receiving adjuvant chemotherapy

Introduction: Colorectal cancer is the most commonly diagnosed gastrointestinal cancer worldwide. For patients without metastatic disease, surgery is the first option used with curative intention, for stage I disease the adequate treatment consists only of surgical excision. In stage III additional adjuvant chemotherapy post-surgery is recommended. In stage II colon cancer, adjuvant treatment remains controversial.We aim to stratify patients according to different criteria, identify those with recurrence within the first year post last cycle of adjuvant chemotherapy and discuss those primary results.Materials and methods: a total of 52 patients who were subject to curative resection of stage II and III colon adenocarcinoma and who were administrated 5 FU based adjuvant chemotherapy were included and were followed for a period of two years. Data analysis was performed.Result: After a mean of 2 years of follow-up, recurrence was identified in 16 patients. None of stage II patients (n=6) and 3 patients in stage III (n=6) experienced recurrence. Patients with Nx cancer (n=30) were detached in separate group. Thirteen of them experienced recurrence (9 patients had relapse within 6 months after surgery - defined as synchronous metastatic disease).Conclusion: Surgery remains the cornerstone of treatment for the majority of colon patients. The selection of optimal chemotherapy for each patient is a complex process and there is a practice evidence gap which remains a significant problem. Our results for relapse are comparable with the reported ones worldwide. The reports suggest that there is still lack of evidence in the adjuvant colon cancer chemotherapy worldwide

Adjuvant Treatment in Colon Cancer

Worldwide, more than 1 million people develop colorectal cancer (CRC) annually. CRC is a major health problem in the Western world and the second most common cause of cancer mortality. To improve performance, the role of chemotherapy for CRC has increased dramatically over the last decade. The vast majority of CRC patients now receive chemotherapy with multiple agents that are currently approved for the treatment in the appropriate setting [1]. However, it is a complex process to select the optimal chemotherapy for each patient and practice evidence gap is still a problem. Some guidelines for the treatment of CRC have been developed to promote the standardization of CRC treatment. Postoperative, or “adjuvant,” systemic therapy has become standard for stage III colon cancer. Adjuvant therapy should also be strongly considered in stage II patients. It is generally recommended for any medically fit patient with stage II cancer with unfavorable factors. The hypothesis that the antitumor activity of the combination agent, including oxaliplatin, irinotecan, bevacizumab, cetuximab in metastatic cure rates, would result in increased adjuvant proved to be often wrong. Although new drug development takes years, targeted drug use can occur more quickly with advanced tests and will be a focus of future work. In addition, efforts will focus on identifying biomarkers that predict response to systemic therapy so that tailored therapy can be initiated. The future of oncology will come with the better understanding of the biology and genetics of the tumor and its host. This will help to develop tailored approach to the patients, including more specific systemic therapy, aimed at molecular targets of the malignant tumor, thus reducing the negative effects. At that time, the treatment of oncological diseases will experience a new era, comparable to the introduction of antibiotics

First line 5-FU-based chemotherapy with/without bevacizumab for metastatic colorectal cancer: one center experience results

Purpose: Colorectal cancer is the second leading cause of cancer mortality in the United States. According to the National Institute of Statistics in Bulgaria for 2012 there have been 2370 newly diagnosed colon cancer and 1664 rectal cancer cases and the total number of registered patients is 29995. Adding Bevacizumab to chemotherapy in patients with metastatic colorectal cancer improves progression-free survival but yet no predictive markers for patient selection have been described and proved in the clinical practice. In our study we examined two plasma biomarkers that may correlate with response to first line Bevacizumab containing chemotherapy in patients with metastatic colorectal cancer.Patients and Methods: 54 patients with metastatic colorectal cancer were assigned to first line 5-Fubased chemotherapy with/without Bevacizumab. The primary end point was progression-free survival, with additional determination of response and toxicity. Blood samples were collected at baseline from all 54 patients prior to initiation of chemotherapy and Bevacizumab. Plasma samples were stored at -80º C until analysis at the Immunology Laboratory at the University Hospital `St. Marina` (Varna, Bulgaria) by a multiple-step sandwich immunoassay Human ELISA VEGF121 and VEGF165 kits.Results: The median progression-free survival for the group treated with CT/Bev was 8.8 months, compared with 5.4 months for the group treated with chemotherapy alone (95% CI, log-rank test P =0.003). The corresponding overall response rates were 19.3% and 10.2% respectively (P < 0.05 for CT/Bev vs CT).Conclusion: The addition of Bevacizumab to 5-Fu based chemotherapy improves progression-free survival duration for patients with metastatic colorectal cancer. We could not find any association between pretreatment plasma levels of VEGF 121 and 165 and worse PFS

Dynamic change of NT- PROBNP in patients with ST-elevation myocardial infarction treated with primary coronary intervention

In the recent years important biomarkers have  emerged as  tools for diagnosis and risk stratification in cardiovascular diseases. Such markers are B- type natriuretic peptide ( BNP) and N- terminal B- type  natriuretic peptide (NT-proBNP).Peripheral blood for the serum levels of  NT-proBNP was taken from patients with STEMI before PCI and 24-48hours after the onset of the symptoms of myocardial infarction. Three of the samples  from all 53 turned out to be positive to NT - proBNP  concentration on Day 0. On day 1 there was   a significant  elevation of the positive samples 11 from 53 patients ( 20,7%) ( p = 0,01). All  patients with STEMI and elevated serum levels of NT- proBNP  have left ventricular ejection fraction <50%.  Our results imply that  NT -proBNP level and its increase in the serum  may be used as a biomarker for the severity of the ischemic heart disease

Impact of the hybrid on the fatty acid composition and thermal stability of cold-pressed sunflower oils produced from 17 newly cultivated hybrids from the region of North Macedonia

Cold-pressed and refined sunflower oils rich in linolenic acid, are particularly susceptible to undesirable changes during deep-frying. The main object of this study was determination of physicochemical parameters such free fatty acids, peroxide value, saponification value, iodine number, density, oxidative stability, and fatty acid composition on cold-pressed oils from 17 newly cultivated hybrids from sunflower from the region of North Macedonia. Results from fatty acid methyl esters indicated Experto hybrid as the high oleic sunflower hybrid with 86.2% of oleic acid. Moreover, iodine number for sunflower oil from this hybrid was 87.5 g I2 per 100 g oil, which was expected due to the high level of monosaturated fatty acid. Negative correlation confirmed inverse relationship between the amounts of oleic acid and values of iodine number (r = –0.896). Opposite, positive correlation between iodine number and amount of linoleic acid (r = 0.892) means that sunflower oils with higher value of iodine number will be thermally unstable and not suitable for deep-frying. Furthermore, the highest value for oxidative stability was measured for cold�pressed sunflower oils obtained from Talento, BG Fil and “Dijamantis hybrids (over 8, 9 and 5 h, respectively). This can be explained by the fact that the oils from those three hybrids had the highest level of oleic acid (83.1, 82.3 and 79.4%, respectively). Monounsaturated fatty acids are more stable then polyunsaturated, which makes sunflower oil suitable for deep-frying. The positive linear correlation between the amount of oleic acid and oxidation stability (r = 0.687) confirmed our statement that a higher amount of monounsaturated fatty acids (as oleic acid) can improve thermal stability and makes the sunflower oils from Talento, Fila BG and Dijamantis hybrids suitable for cooking and deep-frying. The oxidative stability of other examined hybrids at around 3 h can be explained by a dominance of polyunsaturated linoleic acid with levels between 43% and 57.1%. Statistical analysis confirmed our findings due to the negative linear correlation between oxidative stability and amount of polyunsaturated linoleic acid (r = –0.698). We expected higher value for oxidative stability (over 6 h) for cold-pressed sunflower oil from Experto hybrid due to its fatty acid composition. More precisely, the level of oleic acid for this oil was 86.2% and only 4.6% of polyunsaturated linoleic acid. Surprisingly, the oxidative stability of these oils was only 2.64% which can be explained as oxidation of the oil during production. According to the results from our study, we recommended the gap of oleic/linoleic acid as the most important for the determination of the thermal stability of sunflower oils. Finally, physicochemical parameters iodine number and oxidation stability can be a significant parameter for the prediction of the dominance of fatty acids in sunflower oil

Expression of hepatic HMGB1 levels in fructose-induced fatty liver

Проучването на процесите, водещи до хепатоцелуларна клетъчна смърт, е важно за клиничната практика за оценка на тежестта на чернодробното увреждане, както и прилагането на ефективни интервенции за предотвра-тяването й. Наблюденията показват, че и двата процеса - апоптоза и некроза, се активират в относителна степен на определени етапи от прогресията на неалкохолната мастна чернодробна болест - от чернодробна стеатоза, стеа-тохепатит и цироза. В момента най-обещаващият неинвазивен специфичен метод за установяване на некротична клетъчна смърт е нехистоновият ДНК-свързващ протеин с висока подвижност група Б1 (HMGB1). Целта на настоящото изследване бе да се проучат нивата на експресията на HMGB1 и връзката им с чернодробните увреждания и активността на апоптоза в черния дроб на плъхове с фруктозо-индуциран мастен черен дроб. Използвахме мъжки плъхове Wistar, разделени на две групи (n = 7): контролна (на стандартна храна) и експериментална, която приемаше разтвор с високо съдържание на фруктоза (ФРУ) (35% фруктозен царевичен сироп за 16 седмици). Метаболитните нарушения и увреждането на черния дроб са изследвани чрез хистохимични (Н&Е), имунохистохимични, имунологични биохимични тестове. Резултатите по-казаха данни за метаболитен синдром, дребнокапчеста стеатоза, статистически намалени нива на HMGB1, увеличено съотношение на апоптотичните протеини Bax/Bcl2 при плъховете на фруктозна диета.The study of the processes leading to hepatocellular cell death is important for clinical practice to assess the severity of hepatic impairment as well as for the application of effective interventions to prevent it. Observations show that both cell death processes - apoptosis and necrosis are activated at certain stages of the progression of non-alcoholic fatty liver disease from hepatic steatosis, steatohepatitis and cirrhosis. Currently, the most promising non-invasive specific method for detecting necrotic cell death is non-histone DNA-binding protein with high mobility Group B1 (HMGB1). The aim of this study was to investigate the levels of HMGB1 expression and their relationship to hepatic injury and apoptosis activity in rat liver with fructose-induced metabolic syndrome. The results showed data for metabolic syndrome, microvascular steatosis, statistically reduced levels of HMGB1, an increased ratio of Bax/Bcl2 apoptotic proteins in fructose fed rats