SIMULATION OF BIOEQUIVALENCE STUDY ON THE BASE OF DISSOLUTION CURVES

A computer method and software based on the in vitro dissolution ofdrug preparations has been elaborated for the estimation of bioequivalenceusing Microsoft Excel 2007, Visual Basic programming language. Themethod generates a „dissolution surface‖ from the parameters of time (Xaxis),from pH (Y-axis) and from the dissolved amount (A) in % of the drug.This dissolution surface allows the determination of the general dissolutioncurve of the test and reference preparations. By supposing that the absorptionrate constant is known from the literature, the change of the amount ofdissolved drug as the function of time can be determined. On the base of thisfunction the maximum amount of the dissolved drug in the gastrointestinaltract and the AUC can be calculated and the test/reference ratio can bedetermined. In the case of linear pharmacokinetics these ratios are identicalto the ratios of parameters that can be calculated in the circulation. Bygenerating parameters between the allowed biological limits the dissolveddrug – time curves of „volunteers‖ in the necessary number are created withthe randomly generated „residence times‖ and their confidence intervals canbe determined, i.e. on the base of dissolution curves bioequivalence can beestimated

Tumour necrosis factor-α and adenosine in endotoxin shockleading related cardiovascular symptoms

We have observed uncontrollable cardiogenic shock as a cardiovascular manifestation of systemic inflammatory response syndrome (SIRS) leading to death in a 62-year-old woman. The diagnosis of SIRS was based on the demonstration of endotoxinaemia, and highly elevated plasma levels of tumour necrosis factor (TNF)-α, and interleukin (IL)-10. We suggest that these cytokines may contribute to the terminal SIRS-related arrythmias, impaired myocardial contractility, as well as increased vascular permeability. In addition, the increased production of adenosine, a counter-regulatory mediator of inflammation, may also play a role in cardiodepression. We suggest a relationship between the action of TNF-α , IL-10 and adenosine in the pathogenesis of circulatory symptoms described above

Novel breads fortified through oilseed and nut cakes

The nutritive value, the microbiological safety of oilseed cake (OSC) obtained from naked pumpkin seed (PuC), sunflower seed (SC), yellow linseed (LC), and walnut (WnC), and their impact on wheat flour (WF) dough and bread sensory characteristics at 5% and 10% addition ratio were investigated. The OSCs had high protein (34–50%), fat (8–15%), total dietary fibre (23–36%) content and high energy value (383–444 kcal/100 g)). The OSC samples with a minimal exception fulfilled the requirements of feed legislation in force. An increased water absorption, dough development time, and reduced elasticity were observed probably due to the enhanced fiber and protein content. Dough stability increased with WnC, and decreased with PuC or SC addition. Enrichment provided the appearance of a brown bread for WnC, of a half-brown bread for LC. PuC gave an unusual look. The appearance of OSC fortified bread similar to daily bread, was an advantage resulting the 1st rank for 10% WnC bread and the 2nd one for 10% LC bread (P=0.05). The studied OSCs are suitable for food enrichment, however, in case of PuC and SC fortified flour blends, hydrocolloid application is recommended. Our data suggest that the newly developed fortified breads could be a valuable source for healthy nutrition

Haptoglobin Polymorphism: A Novel Genetic Risk Factor for Celiac Disease Development and Its Clinical Manifestations

Background: Haptoglobin (Hp) α-chain alleles 1 and 2 account for 3 phenotypes that may influence the course of inflammatory diseases via biologically important differences in their antioxidant, scavenging, and immunomodulatory properties. Hp1-1 genotype results in the production of small dimeric, Hp2-1 linear, and Hp2-2 cyclic polymeric haptoglobin molecules. We investigated the haptoglobin polymorphism in patients with celiac disease and its possible association to the presenting symptoms. Methods: We studied 712 unrelated, biopsy-proven Hungarian celiac patients (357 children, 355 adults; severe malabsorption 32.9%, minor gastrointestinal symptoms 22.8%, iron deficiency anemia 9.4%, dermatitis herpetiformis 15.6%, silent disease 7.2%, other 12.1%) and 384 healthy subjects. We determined haptoglobin phenotypes by gel electrophoresis and assigned corresponding genotypes. Results: Hp2-1 was associated with a significant risk for celiac disease (P = 0.0006, odds ratio [OR] 1.54, 95% CI 1.20–1.98; prevalence 56.9% in patients vs 46.1% in controls). It was also overrepresented among patients with mild symptoms (69.2%) or silent disease (72.5%). Hp2-2 was less frequent in patients than in controls (P = 0.0023), but patients having this phenotype were at an increased risk for severe malabsorption (OR 2.21, 95% CI 1.60–3.07) and accounted for 45.3% of all malabsorption cases. Celiac and dermatitis herpetiformis patients showed similar haptoglobin phenotype distributions. Conclusions: The haptoglobin polymorphism is associated with susceptibility to celiac disease and its clinical presentations. The predominant genotype in the celiac population was Hp2-1, but Hp2-2 predisposed to a more severe clinical course. The phenotype-dependent effect of haptoglobin may result from the molecule’s structural and functional properties

Вибір пробіотика у пацієнтів з діабетичною ентероколопатією

Objective — to evaluate the comparative efficacy of the use of the coloprotector-synbiotic the probiotic in patients with type 2 diabetes mellitus (T2DM) with functional bowel disorders and intestinal dysbiosis. Materials and methods. 78 patients with T2DM and bloating, abdominal pain or abdominal discomfort, and stool disturbance were examined. The study included patients in the age group of 39 to 68 years (mean 49.3 ± 12.0 years). In all patients, organic intestinal pathology was excluded during colonoscopy. Among the examined patients, patients with diabetic enterocolopathy (DECP) with IBS-like course of the disease prevailed — 41 (52.6 %), the second highest in number were patients with DECP with constipation 20 (25.6 %); in 11 (14.1 %) patients, DECD with diarrhea was diagnosed and in 6 (7.7 %) patients, DECD with flatulence was detected. All patients were randomized to the main (39 patients) and control (39) groups. In the control group, in addition to standard therapy, patients received a probiotic containing combination of Bifidobacterium and Lactobacillus strains of at least 1,0 ∙ 109 CFU. In the main group, patients on the background of standard therapy additionally received coloprotector-synbiotic (1 tablet BID for 4 weeks). Results and discussion. In the complex therapy, the use of coloprotector-synbiotic was more effective compared with the use of a probiotic with an adequate dose of obligate bacteria. The use of coloprotector-synbiotic was especially effective in patients with IBS-like DECP and DECP with diarrhea. Conclusions. The study shows the use coloprotector-synbiotic in the complex therapy of patients with T2DM with DECD is beneficial for correction of gut microbiome.Цель работы — сравнить эффективность колопротектора синбиотика и пробиотика у пациентов с сахарным диабетом 2-го типа (СД2) с функцио­­нальными поражениями кишечника и ки­­шечным дисбиозом. Материалы и методы. Обследованы 78 больных с СД2 и жалобами на вздутие, боль или дискомфорт в животе, нарушение стула. Возраст пациентов составил от 39 до 68 лет (средний возраст — (49,3 ± 12,0) лет)). По данным колоноскопии у всех больных была исключена органическая кишечная патология. У 41 (52,6 %) пациента диагностирована диабетическая энтероколопатия (ДЭКП) с СРК-подобным течением заболевания, у 20 (25,6 %) — ДЭКП с запором, у 11 (14,1 %) — ДЭКП с диареей и у 6 (7,7 %) — ДЭКП с метеоризмом. Всех обследованных разделили на основную (39 больных) и контрольную (39) группы. Лицам контрольной группы назначили базисную терапию, а также пробиотик, содержащий комбинации штаммов Bifidobacterium и Lactobacillus не менее 1,0 ∙ 109 КОЕ. Пациенты основной группы на фоне базисной терапии дополнительно получали колопротектор (по 1 таблетке 2 раза в день в течение 4 нед). Результаты и обсуждение. В комплексе терапии применение колопротектора синбиотика было более эффективным по сравнению с использованием пробиотика с адекватной дозой облигатных бактерий. Применение колопротектора является эф­­фек­тивным, особенно у пациентов с СРК-подобным течением ДЭКП и ДЭКП с диареей. Поэтому у больных с СД2 и ДЭКП в комплекс лечения необходимо включать препараты для коррекции кишечного микробиома. Выводы. Проведенное исследование показало, что колопротектор синбиотика следует рассматривать как препарат выбора для терапии больных СД2 с ДЭКП. Применение колопротектора синбиотика является эффективным, особенно у пациентов с СРК-подобным течением ДЭКП и ДЭКП с диареей.Мета роботи — порівняти ефективність колопротектора синбіотика і пробіотика у пацієнтів з цукровим діабетом 2-го типу (ЦД2) з функціональними ураженнями кишечнику і кишковим дисбіозом. Матеріали та методи. Обстежено 78 хворих на ЦД2 і скаргами на здуття, біль або дискомфорт у животі, порушення випорожнення. Вік пацієнтів становив від 39 до 68 років (середній вік — (49,3 ± 12,0) років)). За даними колоноскопії у всіх хворих було виключено органічну кишкову патологію. У 41 (52,6 %) пацієнта діагностовано діабетичну ентероколопатію (ДЕКП) із СПК-подібним перебігом захворювання, у 20 (25,6 %) — ДЕКП із закрепом, в 11 (14,1 %) — ДЕКП з діареєю і у 6 (7,7 %) — ДЕКП з метеоризмом. Пацієнтів розділили на основну (39 хворих) і контрольну (39) групи. Особам кон­трольної групи призначали базисну терапію, а також пробіотик, що містить комбінації штамів Bifidobacterium і Lactobacillus не менше 1,0 ∙ 109 КУО. Пацієнти основної групи на фоні базисної терапії додатково отримували колопротектор (по 1 таблетці двічі на день упродовж 4 тиж). Результати та обговорення. У комплексі терапії застосування колопротектора синбіотика було більш ефективним порівняно з використанням пробіотика з адекватною дозою облігатних бактерій. Тому у хворих на ЦД2 і ДЕКП в комплекс лікування необхідно включати препарати для корекції кишкового мікробіому. Застосування колопротектора є ефективним, особливо у пацієнтів із СПК-подібним перебігом ДЕКП і ДЕКП з діареєю. Висновки. Проведене дослідження показало, що колопротектор синбіотика слід розглядати як препарат вибору для терапії хворих на ЦД2 із ДЕКП