Intestinal alkaline phosphatase activity as a molecular marker of enterotoxicity induced by single dose of 5-fluorouracil and protective role of orally administered glutamine

Background. One of the critical limitations for the administration of the chemotherapy is the toxicity affecting normal tissue. The main target organs for 5-fluorouracil (5-FU) toxicity in humans and experimental animals are the gastrointestinal tract, bone marrow, and skin. The cytotoxic effects of antimetabolite chemotherapy are based on their role as substrates for the same transport processes and enzymes involved in anabolism and catabolism as the natural substrates. The main goal of our study was to analyze the dose-dependent antiproliferative effects of 5-FU on intestinal mucosa, enterotoxic potential of 5-FU in experimental animals and to test possible protective role of glutamine. Methods. In our study, we used Sprague Dawley rats. The control group of rats included 50 animals, while the groups where either 5-fluorouracil (5-FU) alone or 5-FU and glutamine were administered included 200 animals. All experimental animals were further stratified according to the experimental model (25 animals in each of 8 experimental subgroups of animals). The 5-FU was administered by intraperitoneal application in single dose of 0, 100, 200, 300, and 400 mg of 5-FU per kg of body weight. Water solution of 1% glutamine was prepared daily and administered orally, in volume of 200 ml, for 7 days continuously, after the 7th day of 5-FU administration. Experimental animals were sacrificed 7 days after the administration of 5-FU. The isolation of enterocytes was performed according to the method of Kralovansky et al. In cell homogenate obtained by described method, we determined the protein content using the Biuret method and the DNA content using the Burton reagent. The activities of enzymes alkaline phosphatase (ALP), glutathione S-transferase (GST), glutathione reductase (GR), and glutathione peroxidase (GPX) were determined by kinetic method. All paraffin samples of the small intestine were stained by haematoxiline and eosine(HE method). All the experiments were done in duplicate and analyzed by standard statistical methods. All the experiments were done in duplicate and analyzed by standard statistical methods. Results: Our results of enterotoxicity induced by intraperitonealy administered 5-FU showed statistically significant decrease of DNA content in small intestine samples of experimental animals, decrease in activity of intestinal alkaline phosphatase enzyme and the increase in glutathione-dependent enzymes. The glutamine supplementation reduced 5-FU intestinal toxicity. Conclusion: Intestinal alkaline phosphatase is a good marker of the dose-dependent enterotoxicity induced by 5-fluorouracil

Dedicated Bifurcation Stents

Bifurcations still remain one of the most challenging lesions to be treated in the modern PCI era. They are associated with lower procedural success rates, higher rates of periprocedural complications, and complicated long-term outcomes. Their incidence is assessed to be approximately 15–20%. There is still debate on how should they be treated—one-stent versus two-stent techniques, whether there is a need for obligatory proximal optimization or kissing balloons. Multiple clinical trials have tested different PCI strategies. We will cover theoretical basics of treating bifurcations and describe different types of dedicated bifurcation stents—Nile PAX, Nile SIR, BiOSS Expert, BiOSS LIM, Stentys Tryton, and Axxess Plus. We will discuss the data from studies comparing these bifurcation devices and will show our own experience and results working with these devices. There will be a discussion, tips, and tricks treating bifurcation lesions with dedicated devices—most common pitfalls and how to deal with them

CONTROL SYSTEM OF STEEL BATTERY CHARGER

A practical realization of control of a diode–thyristor bridge is provided in this paper. The proposed control logic is applied to an NiCd accumulator charger. These accumulators are used for power supply of electrical devices and equipment in CFR locomotives. The control system provides a regular mode of NiCd accumulators charging and discharging, and, in this way, their long lifespan. A hardware configuration and a control algorithm for efficient NiCd accumulator charging and preventing overcharging and overheating are provided

Microstructure Formations Resulting from Nanosecond and Picosecond Laser Irradiation of a Ti-Based Alloy under Controlled Atmospheric Conditions and Optimization of the Irradiation Process

This paper presents a study and comparison of surface effects induced by picosecond and nanosecond laser modification of a Ti6Al4V alloy surface under different ambient conditions: air and argon- and nitrogen-rich atmospheres. Detailed surface characterization was performed for all experimental conditions. Damage threshold fluences for picosecond and nanosecond laser irradiation in all three ambient conditions were determined. The observed surface features were a resolidified pool of molten material, craters, hydrodynamic effects and parallel periodic surface structures. Laser-induced periodic surface structures are formed by multi-mode-beam nanosecond laser action and picosecond laser action. Crown-like structures at crater rims are specific features for picosecond Nd:YAG laser action in argon-rich ambient conditions. Elemental analysis of the surfaces indicated nitride compound formation only in the nitrogen-rich ambient conditions. The constituents of the formed plasma were also investigated. Exploring the impact of process control parameters on output responses has been undertaken within the context of laser modification under different environmental conditions. Parametric optimization of the nanosecond laser modification was carried out by implementing an advanced method based on Taguchi’s parametric design and multivariate statistical techniques, and optimal settings are proposed for each atmosphere

Cardiogenic shock - novelty and emerging therapeutic concepts

Кардиогенният шок е състояние на нисък сърдечен дебит, дължащ се на сърдечна дисфункция, което води до тежка органна хипоперфузия с тъканна хипоксия и повишен серумен лактат. Представлява тежко усложнение, чиято честота е около 15% от шоковите състояния, като 2-5% са случаите на КШ, възникнал като усложнение на остра сърдечна недостатъчност. Независимо от разнообразната етиология на КШ, до 80% от случаите възникват като усложнение от остър инфаркт на миокарда. Исхемията, която настъпва, води до дисфункция на миокарда със спад на артериалното налягане и последваща хипоперфузия на тъканите. Ключово е навременното лечение на шока в неговия прешоков стадий. Лечението на рефрактерния КШ е комплексно, като се състои от медикаментозна терапия с инотропи и/или вазопресори и механична циркулаторна поддръжка (MCS). Целта на технологичните средства за MCS е да редуцират работата на сърцето и миокардната нужда от кислород, като същевременно поддържат адекватна системна и коронарна перфузия. Има различен набор от дивайси като IABP, Impella, Tandem Heart, V-A ECMO. Целта на този обзор е да се представят новостите в лечението на кардиогенен шок и да се въведе яснота в терапевтичната схема, въз основа на последните налични препоръки и проучвания. The cardiogenic shock is a state of low cardiac output, primarily due to cardiac dysfunction, which leads to severe organ hypoperfusion with tissue hypoxia and increased lactate levels. It presents a severe complication with a prevalence of around 15% of all forms of shock and 2-5% of the cardiogenic shock is a complications of acute heart failure. Despite the diverse etiology of the cardiogenic shock, up to 80% of the cases are due to acute myocardial infarction. The ischemia, leads to dysfunction of the myocardium cells, which causes a decline in the blood pressure and subsequent tissue hypoperfusion. The most important part is to start the treatment regime as soon as possible in the pre-shock stage. The treatment of refractory cardiogenic shock is complex, as it contains an intravenous therapy with inotropes/vasopressors and mechanical circulatory support (MCS). The MCS devices are supposed to reduce the workload of the heart and the oxygen need of the myocardial cells and in the same time to maintain an adequate coronary and systemic perfusion. There are different MCS devices like IABP, Impella, Tandem Heart, V-A ECMO. The aim of this review article is to present the new trends in the treatment approach to cardiogenic shock and to bring clarity in the treatment regimes, based on the latest studies and guidelines

Compression of the left main coronary artery by a pulmonary artery aneurysm – treated with endovascular approach

Аневризмалното разширение на пулмоналната артерия е рядко заболяване с неспецифични клинични симптоми, което може да доведе до сериозни усложнения, като дисекация или руптура на пулмоналната артерия и компресия на ствола на лява обща коронарна артерия. Усложненията и асоциацията с пулмонална хипертония са свързани с висока смъртност. Стандартният подход за лечение е чрез хирургична корекция на аневризмата или перкутанна коронарна интервенция при пациенти с клинично сигнификантна компресия на ствола на лявата коронарна артерия от аневризма на пулмоналната артерия. В тази статия представяме клиничен случай на 73-годишен полиморбиден пациент, представящ се с остър коронарен синдром, причинен от външна компресия на ствола на лява коронарна артерия от пулмонална аневризма. Поради високия риск от хирургична интервенция, пациентът беше лекуван ендоваскуларно, чрез стентиране на компресираната коронарна артерия с успешно възстановяване на кръвотока и клинична стабилизация на състоянието. В нашия случай перкутанната интервенция със стентиране доказа, че това е безопасен и ефективен вариант на лечение за строго подбрани пациенти, които са с висок оперативен риск. Pulmonary artery aneurysms (PAAs) are rare with non-specific clinical presentation but may lead to serious complications such as pulmonary artery dissection, rupture and compression of the left main coronary artery (LMCA). Their complications and PAA association with pulmonary hypertension lead to significant morbidity and mortality. The standard treatment strategy is surgical correction of the aneurysm, however percutaneous coronary intervention in patients with clinically significant compression of the LMCA, due to PAA should be considered as a possible treatment approach. In this article, we present a case report of a 73-year-old with polymorbidity, presenting with an acute coronary syndrome, caused by extrinsic compression of the LMCA by PAA. Due to the high surgical risk, we adopted an endovascular approach with stenting of the compressed LMCA with successful restoration of the blood flow and clinical stabilization. In this case, a percutaneous coronary intervention proved to be a safe and effective treatment option for selected patients, who are at high operative risk.

Hemodynamics in mitral regurgitation – before and after correction with MitraClip

Хемодинамичните промени при митрална инсуфициенция са в основата на тригерирането на симптоматика при пациента и поддържането на сърдечната недостатъчност. Редица ендоваскуларни методи за корекция на мит- ралната регургитация успешно противодействат на патологичната хемодинамика и по този начин успяват да по- добрят както проявите на сърдечна недостатъчност, така и симптоматиката на пациента. В настоящата статия се разглежда физиологията на митралната клапа и промените, настъпващи при налична митрална инсуфициенция. Представени са особеностите в хемодинамиката на лявото предсърдие в условията на митрална инсуфициенция и след някои видове транскатетърното лечение – edge-to-edge корекция на клапата с MitraClip и имплантацията на оклудер при парапротезна митрална инсуфциенция. Промяната в левопредсърдните показатели, отчетена непос- редствено след корекция на порока, има стойност както за оценка на непосрествения процедурен успех, така и за прогнозата на пациента. Haemodynamic changes in mitral regurgitation underlie triggering of patient’s symptoms and development of heart failure. A number of endovascular methods for the correction of mitral regurgitation successfully counteract pathological hemodynamics and thus manage to improve both the manifestations of heart failure and the patient's symptoms. This article is a review of the physiology of the mitral valve and the changes that occur in the presence of mitral regurgitation. The peculiarities of the hemodynamics of the left atrium in the conditions of mitral regurgitation and after some types of transcatheter treatment – edge-to-edge correction of the valve with Mitraclip and the implantation of an occluder in paraprosthetic mitral regurgitation are considered. The change in left atrial parameters immediately after correction of the defect is of value both for the assessment of immediate procedural success and for the patient's prognosis

Endovascular treatment of type „A“ and type „B“ dissection of the aorta

През периода от март 2014 г. до май 2018 г. в нашия сърдечно-съдов център беше проведено ендоваскуларно лечение на аортна дисекация тип А и тип Б при общо 70 пациенти. Пациентите са разделени в две групи, съответно аортна дисекация тип А (14 души) и тип Б (56 човека). Проведен е описателен анализ по група, след което се извърши сравнение между двете групи пациенти. Целта на проучването е да се установи ефективността на ендоваскуларното лечение при тип А и тип Б дисекация на аортата. В резултат на проучването се за първи път в България се натрупват данни за демографските особености и рисковия профил на тези пациенти. Изследват се ендоваскуларните опции за лечение на аортна дисекация (АД) тип А и тип Б, както и на малперфузионния синдром, като се доказва тяхната ефективност и безопасност. В резултат на проучването се доказва, че ендоваскуларното лечение при АД тип А и тип Б води до значително увеличаване в размера на истинския и редукция на фалшивия лумен, в резултат на което се подобрява перфузията и се понижава рискът от развитие на аневризма и руптура. Наличието на ендолийк и персистираща комуникация между фалшивия и истинския лумен са най-честите причини за реинтервенция, като ендоваскуларните методи са най-често първа линия за лечението им и се доказват като ефективни и безопасни. Лечението на дисекацията на аортата тип А и Б не е еднократен акт, а изисква периодичен диагностичен контрол и при необходимост – оперативни и/или ендоваскуларни корекции на възникналите усложнения. During the period from March 2014 to May 2018, endovascular treatment of aortic dissection type A and type B was carried out in a total of 70 patients. Patients were divided into two groups, aortic dissection type A (14 patients) and type B (56 patients), a group-by-group descriptive analysis was conducted, and then a comparison was done between the two patient groups.  The aim of the study was to establish the effective use of endovascular treatment in type A and type B aorta dissection. As a result of the survey, data on the demographic characteristics and risk profile of these patients are accumulated for the first time in Bulgaria. Endovascular treatment options for the treatment of aortic dissection type A and type B, as well as malperfusion syndrome, are examined, demonstrating their effectiveness and safety. As a result of the study, it is proven that endovascular treatment in aortic dissection type A and type B leads to a significant increase in the size of the true lumen and reduction of the false lumen, which leads to an improvement in perfusion and reduces the risk of developing an aneurysm and rupture.  The presence of endoleak and persistent communication between the false and the real lumen are the most common causes of re-intervention, such as endovascular options are most often the first line for their dealing and are proven to be effective and safe.  Treatment of dissection of the aorta type A and B is not a one-time act, but requires periodic diagnostic control and, if necessary, surfery and/or endovascular corrections of the complications that have arisen

Determination of Pefloxacin in Serum and Pharmaceutical Forms by Derivative Spectrophotometry

A method for the direct determination of pefloxacin in serum and pharmaceutical forms (tablets and ampoules) has been developed, based on the use of second-order derivative ultraviolet spectra. Spectrophotometric assay of pefloxacin in tablets and ampoules was carried out in 0.1 mol/L NaOH, while in serum it was performed in 0.1 mol/L NaOH with the addition of sodium dodecylsulfate, in 337-347 nm wavelength range. Linear calibration curves were obtained in the concentration ranges 2-30μg/mL pefloxacin for tablets and ampoules and 0.12-5μg/ mL for serum samples. Relative error of determination, as criterion for accuracy, was less than 1%, while the precision was better than 4ng/ml. The minimum detectable concentration of pefloxacin in serum was 15ng/mL

Changes of biochemical parameters in rat intestinal mucosa induced by methotrexate and effects of enteral administration of glutamine

BACKGROUND: Rapidly proliferating crypt cells of the intestinal epithelium, the precursors of the mature enterocytes, are extremely sensitive to the effects of cytostatic agents. We investigated the effects of the methotrexate on rat intestinal mucosa in order to get the information on biochemical indicators of intestinal damage. METHODS: Biochemical parameters were investigated in isolated intestinal mucosa of Sprague-Dawley rats, previously treated with methotrexate by intraperitoneal administration. Glutamine was dissolved in water and administered orally. RESULTS: The activity of glutaminase and alkaline phosphatase showed the enzymatic response to different doses of methotrexate. The activity of both enzymes was significantly lower in the mucosa of treated animals, compared to control group. CONCLUSION: Minimal mucosal damage and regeneration time is dose dependent and influenced by the dosage schedule of antitumor therapy