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

Liminal sites : designing marginal space in Broadmeadows

Liminal sites are those on the verge of change, between boundaries and in a temporary state of ambiguity. Throughout my practice as an architect I was aware of the existence of such spaces. I was also aware that they were rarely the product of my intentional design effort. Because of that to me these spaces were precious. They represent moments in space of ambiguous function and questionable beauty but also moments I sought out everyday. This masters research is my way of refocusing my practice to engage with these types of spaces. The sense that this search will take me outside of my understanding of architecture lead me to chose to undertake it as a masters in landscape architecture. My main research question is: How can a designer construct a liminal site? The research concentrates on four central themes - development of a definition of the term "Liminal Site", transitional forms between public and private space, user-designer relationship and the role of narrative sequencing in varying the user-designer relationship. The research is conducted by project through a series of design exercises based in a surface car park as Broadmeadows town centre in outer north Melbourne. The research employs found and designed spaces as precedent sites, analysis of film as examples of designed narrative sequences, analysis of personal driving patterns for users engagement with narrative and the testing of the identified narrative sequencing techniques on the selected site. The research defines a liminal site as an experiential space which sits on the threshold of public and private and is able to temporarily shift from one to the other through the engagement with users. I identify three types of narrative sequencing techniques which can be employed in the design of a liminal site: linear, recurrent and concurrent. Each of these methods creates an unique connection between the designer and the user. The success of these techniques in constructing a liminal site varies. The research concludes that "liminal sites" are the product of a collaborative relationship between designer and user. Their generation can be achieved by the specific transfer of meaning occurring through the embedding and decoding of narrative sequences, performed by both user and designer

Metabolic changes in experimental model of metabolic syndrome - induced by high-fructose diet in rats

The global epidemic of metabolic syndrome (MS) correlates with changes in the environment, feeding, behavior and lifestyle, leading to obesity, glucose intolerans, dyslipidemia and elevated cardiovascular risk. AIM: The aim of our study was to develop an experimental model of the MS in rat that imitate the investigated metabolic disorders using high-fructose diet. METHODS: We used two groups: control group (C)- rats, maintained on plain water (n=6); fructose group (FRU)- rats received 12.5% high-fructose corn syrup in drinking water for 12 weeks (n=6). The main markers of metabolic abnormalities (glucose, total cholesterol, triglycerides, uric acid, body and organs weight), the markers of oxidative stress (malondialdehyde (MDA), total thiols) and C-reactive protein (CRP) - inflammatory marker were measured. RESULTS: Our data showed hypercholesterolemia, hyperglycemia, hyperuricemia and significant elevated levels of CRP, MDA, body and organs weight, and inhibited antioxidant defense in fructose- drinking rats. CONCLUSION: The experimental model will support our studies associated with pathophysiology and pharmacology of MS

Structural changes and wage inequality in the Bulgarian economy

In light of the growing concern about the economic and social costs of high income inequality, the paper analyses wage inequality in Bulgaria in the context of the structural changes taking place in the economy. For this purpose, we first estimate wage inequality in the country over the period 2000-2016 by using the inequality decomposition method proposed by Pyatt, Chen and Fei (1980). Then, we analyse the differences in wages depending on economic activity, region and educational attainment. The results show that wages are the most significant source of income inequality in Bulgaria and that their contribution to overall inequality increases significantly during the analysed period. Furthermore, the growing role of the service sector at the expense of agriculture and industry is associated with increasing wage differences across economic sectors, regions and levels of education, which together shape the magnitude and the dynamics of wage inequality

The GG rs292001 genotype prevails in seronegative for ANA and anti-dsDNA antibodies patients with lupus nephritis

Rs292001 is single nucleotide polymorphism in non-coding regions of C1QA gene. C1q is subcomponent of the C1 first component of the classical pathway of complement activation. Rs292001 was investigated for association with some conventional immunological markers of lupus nephritis activity in SLE patients - levels of C1q, C3, C4, anti-C1q, anti-nuclear (ANA) and anti-dsDNA autoantibodies.Genomic DNA was isolated from peripheral blood of 18 patients with biopsy-proven lupus nephritis (LN). SNP genotyping for the presence of rs292001 was performed by quantitive real-time PCR method. Presence of complement C1q, C3 and C4 and anti-C1q autoantibodies was screened by ELISA. ANA and anti-dsDNA antibodies were detected by indirect immunofluorescence.We found that GG rs292001 genotype prevailed in seronegative for ANA and anti-dsDNA antibodies LN patients (p=0.008; p<0.012). The AA rs292001 genotype showed a trend towards lower serum C1q levels.These results reaffirm a previously established probable protective role of G allele against the clinical activity of the SLE

Preauricular sinus: Incidence and inheritance

Introduction: The preauricular sinus (PAuS) is a malformation of the auricula pinna. The structure may present isolated or as a component of a number of oto-renal syndromes.Aim:  The aim of this study was to establish the incidence of PAuS in a Bulgarian cohort and propose a model for its inheritance, based on the transgenerational mechanisms derived from the genealogic trees of interviewed individuals.Materials and Methods: A total of 100 healthy individuals were prospectively evaluated for the presence of a PAuS on a random cohort sampling principle. A descriptive statistical approach was used when categorizing the individual features. Individuals were also assessed in terms of their genealogies and presence of renal symptoms.Results: Of all assessed individuals, 3% (n=3) had a structure complying with the criteria for a PAuS. No one having the structure reported renal symptoms. The genealogical trees were characteristic of a dominant trait with incomplete penetrance.Conclusion: The incidence of PAuS in our study cohort is similar to that of other Caucasian cohorts and gives a rare modern glimpse into the transgenerational inheritance of the PAuS, together with data on the oto-nephrological syndromes

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

Risk Of Development Of Solid Tumors In Patients With Systemic Lupus Erythematosus

Системният лупус еритематозус (СЛЕ) е автоимунно заболяване, характеризиращо се с продуциране на различни автоантитела, активиране на комплемента и отлагане на имунни комплекси. Връзката между СЛЕ и рака отдавна е установена. При пациенти със СЛЕ честотата и рискът от злокачествено заболяване се увеличава за белодробен карцином, рак на шийката на матката, хепатоцелуларен карцином и др. В същото време честотата на карцином на гърдата, на простатната жлеза и яйчниците е ниска в редица проучвания на СЛЕ пациенти.Известни са редица фактори, които могат да допринесат за развитието на злокачествени заболявания при СЛЕ. В този преглед ние представяме някои по-често срещани солидни тумори и тяхната честота при пациенти със СЛЕ, както и факторите, които влияят на туморогенезата в условията на автоимунно заболяване.Systemic lupus erythematosus (SLE) is an autoimmune disease, characterized by production of different autoantibodies, complement activation, and immune complex deposition. An association between SLE and cancer has long been known. In patients with SLE, the incidence and risk of overall malignancy is increased for lung cancer, cervical cancer, liver cancer, and etc. Conversely, the incidences of prostate, breast and ovarial cancers are decreased in a number of studies of SLE patients.There are many factors, which can contribute to the development of malignancies in SLE. In this review we present some more common solid tumors and their incidence in SLE patients as well as the factors that affect tumorigenesis in conditions of autoimmune disease

KINETIC MODELING ON AMIDE HYDROLYSIS, DRUG RELEASE AND MUCOSAL PERMEATION OF INDOMETHACIN IN THE COMPOSITION OF SELECTED SEMISOLID VEHICLES

The present study aims to reveal the role of a semi-solid vehicle in the composition of Indomethacin dosage forms for their physical and chemical stability, in vitro and ex vivo behavior. Three types of hydrogels and emulgels were prepared with gelling agents Methylcellulose 2%, Poloxamer 407 20% and Carbomer 940 1%. Each preparation was observed for physical and chemical stability at 5°C and 25°C within 3 months. Test formulations, along with USP standard Indomethacin gel and combined marked product Indextol,were subjected to in vitro drug release test and ex vivo permeation study, using porcine intestinal mucosa on Franz diffusion cell. A hypothesis was built to predict steady-state plasma concentration (Css) of Indomethacin for each formulation following mucosal administration. Results revealed sustained chemical stability of all emulgels for the period observed and significantly lower chemical stability of the corresponding hydrogels. Methylcellulose hydrogel (at both temperatures) and emulgel (at 25°C) showed signs of phase separation, while all other formulations kept their physical appearance for the duration of the study. Methylcellulose emulgel along with Poloxamer 407 hydrogel showed highest cumulative drug release in 12 hours (58.01% and 55.00%, respectively). Same formulations exhibited also highest drug permeation rate (Jss) through mucosa (10.55 µg.cm-2.h-1 and 13.20 µg.cm-2.h-1, respectively) and highest predicted value of plasma concentration (Css up to 100.49 µg.l-1 and 125.71 µg.l-1, respectively), whereas highest drug deposition in mucosal tissue was detected for Poloxamer 407 emulgel (2.1 mg.cm-3)

Neurotoxicity of cancer agents

Невротоксичните ефекти на химиотерапията се появяват относително често и са причина за модификация на дозата на медикаментите - дозолимитираща токсичност. Рискът от развитие на невротоксичност се увеличава с повишаване на приложената доза и за разлика от миелотоксичността (основния ограничаващ фактор при повечето химиотерапевтични режими), която може да бъде преодоляна с растежни фактори или трансплантация на костен мозък, няма стандартно поведение, което да я ограничи.Противотуморните препарати водят до два типа токсичност - периферна невротоксичност, състояща се основно от периферна невропатия и централна невротоксичност, която включва от незначителни когнитивни увреждания и дефицити до енцефалопатия с деменция или дори кома.Не съществуват утвърдени алгоритми за поведения и профилактика на невротоксичността, причинена от противотуморните препарати. Поведението основно се свежда до редукция на дозата или отлагане във времето на приложението, особено при пациенти, които са с по-висок риск от развитие на невротоксични странични ефекти. На този етап не съществуват невропротективни агенти, които се препоръчват за стандартна употреба при развитие на невротоксичност.Neurotoxic side effects of chemotherapy occur frequently and are often a reason to limit the dose of chemotherapy. Chemotherapy dosing is often limited due to a frequently occurring side effect of the treatment - neurotoxic. The risk of neurotoxicity is increased by the possibility of higher dose usage, since bone marrow toxicity (the major limiting factor in most chemotherapeutic regimens) can be overcome with growth factors or bone marrow transplantation.Chemotherapy may cause both peripheral neurotoxicity, consisting mainly of a peripheral neuropathy, and central neurotoxicity, ranging from minor cognitive deficits to encephalopathy with dementia or even coma. Neurotoxicity caused by the chemotherapy can be of two types - peripheral, mainly consisting of peripheral neuropathy and central, from minor cognitive deficits through encephalopathy with dementia to even coma.Data management and neuroprotective agents are still in discussion and there are no current accepted guidelines yet. Management mainly consists of cumulative dose-reduction or lower dose-intensities, especially in patients who are at higher risk to develop neurotoxic side effects. None of the specific neuroprotective agents can be recommended in daily practice for standard use at the moment, and further studies are needed to confirm their beneficial effects