Utjecaj esencijalnog ulja čajevca (Melaleuca alternifolia) kao dodatka prehrani na proizvodna svojstva, oksidacijski status krvi i liječenje kokcidioze u kokoši nesilica

Aim of this experiment was to investigate the effect of tea tree (Melaleuca alternifolia) essential oil in the nutrition of laying hens on table egg production, antioxidant activity and potential as a natural anticoccidial drug. A total of 360 Lohmann Brown laying hens aged 54 weeks were divided into 3 different treatment diets, supplemented with 0 (T1), 40 (T2) and 80 mg/kg (T3) tea tree essential oil, respectively. Each treatment was replicated 4 times with 30 birds each. The experiment lasted 56 days in total (55 to 62 weeks of hen age). The 56 day experimental period was divided into 2 periods of 28 days duration each: period 1 (55 to 58 weeks of hens age) and period 2 (59 to 62 weeks of hens age). The hens’ blood oxidative status, including glutathione peroxidase (GSHPx), superoxide dismutase (SOD) activity and concentration of malondialdehyde (MDA), and the anticoccidial effects of tea tree on Eimeria spp. compared to the unsupplemented control treatment, were evaluated. With the diet supplemented with tea tree essential oil, hen-day egg production improved significantly (P0.05). The anticoccidial activity of tea tree essential oil caused a significant (P 0,05). Antikokcidijalna aktivnost esencijalnog ulja čajevca utjecala je na znakovito smanjenje (P < 0,05) broja oocista Eimeria spp. po kokoši. Na temelju rezultata ovoga istraživanja može se zaključiti da je dodatak esencijalnog ulja čajevca povećao dnevnu proizvodnju jaja i smanjio formiranje oocista, stoga se ono može upotrijebiti kao profilaktički dodatak prehrani kokoši nesilica. Također se pokazalo da je ulje čajevca važno u aktivaciji antioksidacijskog zaštitnog sustava u kokoši

Double-blind, randomised, placebo-controlled trial on the effect of L-carnitine and L-acetylcarnitine on sperm parameters in men with idiopathic oligoasthenozoospermia

Carnitine is essential for energy metabolism and spermatozoa maturation. Combining L-carnitine and L-acetylcarnitine with micronutrients has been investigated as a treatment for infertility in men. We evaluated the effects of a therapeutic formulation, Proxeed Plus, on sperm parameters in oligoasthenozoospermic men. This prospective, randomised, double-blind, placebo-controlled clinical trial involved 175 males (19-44 years) with idiopathic oligoasthenozoospermia who failed to impregnate their partners (12 months). Males received Proxeed Plus or placebo for 3 and 6 months. Sperm volume, progressive motility and vitality significantly (p lt 0.001) improved after 6 months compared to baseline. Sperm DNA fragmentation index significantly decreased compared to baseline (p lt 0.001) and the 3-month therapy (p = 0.014) in treated men. Increased seminal carnitine and alpha-glucosidase concentration also positively correlated with improved progressive motility. Decreased DNA fragmentation index was the good predictor of progressive sperm motility >10%, and simultaneous measurement of changes in sperm vitality and DNA fragmentation index gave the highest probability of sperm motility 10% (AUC = 0.924; 95% CI = 0.852-0.996; p lt 0.001). Logistic regression analyses revealed DNA fragmentation index decrease as the only independent predictor of sperm motility 10% (OR = 1.106; p = 0.034). We have demonstrated the beneficial effects of carnitine derivatives on progressive motility, vitality and sperm DNA fragmentation. Combining metabolic and micronutritive factors is beneficial for male infertility

Influence of immediate release tablet formulation on dissolution profile of paracetamol

Introduction: Paracetamol is analgesic and antipyretic, which is usually in the form of an immediate release tablet formulations. Therapeutic effects in terms of the speed and intensity of the analgesic effect is dependent on speed of liberation from formulation. Aim: The aim of this work was to determine and compare dissolution profiles of 4 paracetamol immediate release tablet formulations and to determine influence of excipients on kinetic of paracetamol dissolution. Materials and Methods: Dissolution profiles of paracetamol tablets were determined using method with paddles and phosphate buffer pH 6.8 as a medium. Release of paracetamol was followed 60 minutes (using 6 time points). Concentration of paracetamol was measured using UV/Vis spectrophotometric method (243 nm). Dissolution profiles were compared using model-independent method (difference factor and similarity factor), statistic method (ANOVA-based method and pair Student's T-test, p<0.05) and model dependent methods (to determinate the release kinetics of paracetamol). Results: All formulations in the first 45 minutes liberated more than 85 % of the labled content. Formulation D, which contained superdesintegrator, released 90% of the content in the first 5 minutes. Though based on values of difference and similarity factors formulations are, not significantly different, ANOVA-based method showed that formulation A and B, B and C, as well as formulation B and D do statistically differ in all 6 time points, meaning they have parallel profiles. The release of paracetamol from formulations A and D is best described by the first order kinetic model, while the release of formulations B and C by the logistic model. Conclusions: The release kinetic of paracetamol is mostly influenced by the type of superdisintegrants and lubricants. Formulation with superdisintegrant technology OptiZorb® demonstrated fastes release rate and thus it is expected to produce the fastest pharmacodynamic effect.

Correlation between coagulation and inflammation state in patients with diabetes mellitus type 2 in relation to gender differences: Is there any impact of eight-week exercise training?

Background/Aim. The hypercoagulable state and inflammation state in diabetics has been widely studied by previous researchers, but there is a lack of research about a possible impact of exercise training on this relationship. The aim of this study was to assess and compare correlation between the coagulation and inflammation status in patients with type 2 diabetes mellitus taking into account the gender differences as well as an impact of the 8-week exercise training on the correlation coefficient and parameters of the inflammation and coagulation state. Methods. A total of 60 patients in stable clinical condition and well-regulated diabetic status passed through all phases of the study. The exercise training included the exercise program as interval training with estimated intensity uphill to 75% of a maximal heart rate in particular individual, 5 times a week for 8 weeks, and walking for 30 minutes with a speed of 5 km/h, 5 times a week for 8 weeks. Further fibrinolytic, coagulation and inflammatory parameters were analyzed before and after the study: D-dimer, von Willebrand factor (vWF), fibrinogen, high sensitivity CRP (hs-CRP), leukocytes, thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT) and coagulation factors: FII, FV, FVII and FX. Results. Our research showed a statistically significant reduction in the mean vWF levels after intervention both at the males (p < 0.001) and females (p < 0.001). According to a correlation analysis between hs-CRP and fibrinogen, there was a positive correlation as baseline both at the males (p < 0.05, r = 0.492) and females (p < 0.01, r = 0.516) which became weaker in the males (p < 0.01, r = 0.449) and disappeared in the females (p < 0.05, r = 0.059) after intervention. The correlation which existed as baseline in the males between D-dimer and either hs-CRP (p < 0.01, r = 0.633) or fibrinogen (p < 0.01, r = 0.673) as well as the correlation between hs-CRP and FII (p < 0.01, r = 0.728), FV (p < 0.05, r = 0.366), FVII (p < 0.05, r = 0.373) coagulation as well as between D-dimer and FII (p < 0.01, r = 0.851), FVII (p < 0.05, r = 0.367)was absent in the females. Our research demonstrated a weakening correlations in the males after intervention between D-dimer and hs-CRP (p < 0.05, r = 0.378), between hs-CRP and FII (p < 0.01, r = 0.501), FV (p < 0.05, r = 0.298), FVII (p < 0.05, r = 0.351) as well as between D-dimer and FII (p < 0.01, r = 0.759), and FVII (p < 0.05, r = 0.296). The increase of the FX values (p < 0.05) in the females after intervention suggested the possible antiinflammatory effect of exercise training. Conclusion. According to previous research, the higher levels of vWF was associated with a risk of cardiovascular disease in people with type 2 diabetes mellitus and vWF may be a risk factor unique to these populations. We demonstrated that the 8-week exercise training can significantly reduce the value of vWF in the males and females, suggesting a potential beneficial effect on the endothelial function parameters. Our research demonstrated a stronger correlation between the coagulation and inflammation parameters as baseline in the males than in the females with type 2 diabetes mellitus. According to our results, the 8-week exercise training lead to a weakening of the strength of correlation between the coagulation and inflammation parameters in the males and complete disappearance of this correlation in the females, suggesting a unique effect of exercise training that should be explored in future research

Economic effects of cattle meat production of different genetic provenience in mountainous areas of Northern Kosovo and Metohia

In this research we examined the influence of two different genotypes (Simmental and crossbreed of Simmental and busa) on: weight gain(y), feed consumption for weight gain(x) per month during the fattening period average productivity (A. P.), represented by relation of total weight gain and consumed nutritive units, marginal weight gain (M.G.), which represents ratio of increased weight gain and increased input of nutritive units, as well as weight gain elasticity for achieved production level i. e. ratio of proportional weight gain increment and proportional increment of nutritive units during the fattening period. Fattening results show that cross-breed F1 achieved lower daily weight gain for 11,24% and higher feed consumption per growth unit (7,041 : 5,975) than Simmental cattle. Average productivity has a benefcial trend in Simmental cattle in comparison with cross-breed F1 generation. Coeffcient of correlation among feed and weight gain during the fattening period in cross-breed was 0,733, while in Simmental breed it was 0,569. The achieved economic effects of fattening are a consequence of genetic predisposition of genotypes investigated, since fattening process evolved in identical conditions, so that non-genetic variance could be conditionally neglected

Continuing medical education in Serbia with particular reference to the Faculty of Medicine, Belgrade

Background/Aim. Continuing Medical Education (CME), conceptualised as lifelong learning (LLL) aims at improving human resources and continuing professional development. Various documents of European institutions underline its key importance. This paper therefore tries to analyse the current status of CME and the main deficits in the delivery of LLL courses at medical faculties in Serbia with special consideration of the Faculty of Medicine in Belgrade with detailed financial data available. Methods. Data of 2,265 medical courses submitted in 2011 and 2012 for accreditation were made available, thereof 403 courses submitted by 4 medical faculties in Serbia (Belgrade, Kragujevac, Niš, Novi Sad). A subset of more detailed information on 88 delivered courses with 5,600 participants has been provided by the Faculty of Medicine, Belgrade. All data were transferred into an Excel file and analysed with XLSTAT 2009. To reduce the complexity and possible redundancy we performed a principal component analysis (PCA). Correlated component regression (CCR) models were used to identify determinants of course participation. Results. During the 2-year period 12.9% of all courses were submitted on preclinical and 62.4% on clinical topics, 12.2% on public health, while 61.5% of all took place in Belgrade. The subset of the Faculty of Medicine, Belgrade comprised 3,471 participants registered with 51 courses accredited and delivered in 2011 and 2,129 participants with 37 courses accredited and delivered in 2012. The median number of participants per course for the entire period was 45; the median fee rates for participants were 5,000 dinars in 2011 and 8,000 in 2012, resulting together with donations in a total income for both years together of 16,126,495.00 dinar or almost 144,000.00 euro. This allowed for a median payment of approximately 90 eur per hour lectured in 2011 and 49 euro in 2012. The 2 factors, D1 (performance) and D2 (attractiveness), identified in the PCA for Medical Faculties in Serbia, explain 71.8% of the variance. Most relevant are the duration of the courses, credit points, and hours per credit point gained by lecturers and participants respectively. In the PCA for Belgrade D1 and D2 explain 40.7% of the total variance. The CCR on the number of participants reveals the highest positive impact from the number of lecturers per course and the expenditure on amenities, the highest negative impact from the total income collected per participant. Conclusion. The faculties of medicine in Serbia should reconsider the entire structure of their organisation of CME, especially to improve the quantity and quality of registration limit the course fee rates per hour and reduce administrative and other costs request lecturing in CME programmes as obligatory for academic promotion and organise a focussed marketing. [Projekat Ministarstva nauke Republike Srbije, br. 175042

Circulating palmitoleic acid is an independent determinant of insulin sensitivity, beta cell function and glucose tolerance in non-diabetic individuals: a longitudinal analysis

Aims/hypothesis: Experimental studies suggest that the fatty acid palmitoleate may act as an adipocyte-derived lipid hormone (or ‘lipokine’) to regulate systemic metabolism. We investigated the relationship of circulating palmitoleate with insulin sensitivity, beta cell function and glucose tolerance in humans. Methods: Plasma NEFA concentration and composition were determined in non-diabetic individuals from the Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) study cohort at baseline (n = 1234) and after a 3 year follow-up (n = 924). Glucose tolerance, insulin secretion and beta cell function were assessed during an OGTT. Whole-body insulin sensitivity was measured by a hyperinsulinaemic–euglycaemic clamp (M/I) and OGTT (oral glucose insulin sensitivity index [OGIS]). The liver insulin resistance index was calculated using clinical and biochemical data. Body composition including fat mass was determined by bioelectrical impedance. Results: Circulating palmitoleate was proportional to fat mass (r = 0.21, p &lt; 0.0001) and total NEFA levels (r = 0.19, p &lt; 0.0001). It correlated with whole-body insulin sensitivity (M/I: standardised regression coefficient [std. β] = 0.16, p &lt; 0.0001), liver insulin resistance (std. β = −0.14, p &lt; 0.0001), beta cell function (potentiation: std. β = 0.08, p = 0.045) and glucose tolerance (2 h glucose: std. β = −0.24, p &lt; 0.0001) after adjustment for age, sex, BMI, adiposity and other NEFA. High palmitoleate concentrations prevented the decrease in insulin sensitivity associated with excess palmitate (p = 0.0001). In a longitudinal analysis, a positive independent relationship was observed between changes in palmitoleate and insulin sensitivity over time (std. β = 0.07, p = 0.04). Conclusions/interpretation: We demonstrated that plasma palmitoleate is an independent determinant of insulin sensitivity, beta cell function and glucose tolerance in non-diabetic individuals. These results support the role of palmitoleate as a beneficial lipokine released by adipose tissue to prevent the negative effects of adiposity and excess NEFA on systemic glucose metabolism

In silico–in vitro estimation of lipophilicity and permeability association for succinimide derivatives using chromatographic anisotropic systems and parallel artificial membrane permeability assay

Passive permeability is one of the key features that determine absorbability and one of the most studied properties in the early phases of drug development. Newly synthesized succinimide derivatives from two different series (1-aryl-3-methylsuccinimides and 1-aryl-3-ethyl-3-methylsuccinimides) with high biological potential have been subjected to estimation of their passive permeability and their association with (a) experimentally obtained anisotropic lipophilicity, (b) in silico–calculated lipophilicity and (c) in silico–predicted permeability and absorbability. Non-cellular-based parallel artificial membrane permeability assay was applied for quantifying their passive permeation, expressed as logPapp. Passive permeation was governed by the lipophilicity of the analysed compounds, and anisotropic lipophilicity was related with statistically significant passive transcellular diffusion (r2 = 0.614, P < 0.001). Moreover, experimentally determined passive permeability, logPapp, was statistically significantly associated with both in silico–predicted absorption constant, ka (r2 = 0.7886, P < 0.001), and human intestinal absorption (HIA) in percentage (r2 = 0.484, P < 0.001), respectively. However, there was no statistically significant relationship between experimentally obtained permeability on non-cellular-based model and in silico–predicted Caco-2 permeability based on the predictions conducted on two different software. Based on the obtained results, anisotropic systems are promising surrogates for determining lipophilicity, except for compounds with acidic functional groups that are completely ionized under (pH = 7.4)

In silico–in vitro estimation of lipophilicity and permeability association for succinimide derivatives using chromatographic anisotropic systems and parallel artificial membrane permeability assay

Passive permeability is one of the key features that determine absorbability and one of the most studied properties in the early phases of drug development. Newly synthesized succinimide derivatives from two different series (1-aryl-3-methylsuccinimides and 1-aryl-3-ethyl-3-methylsuccinimides) with high biological potential have been subjected to estimation of their passive permeability and their association with (a) experimentally obtained anisotropic lipophilicity, (b) in silico–calculated lipophilicity and (c) in silico–predicted permeability and absorbability. Non-cellular-based parallel artificial membrane permeability assay was applied for quantifying their passive permeation, expressed as logPapp. Passive permeation was governed by the lipophilicity of the analysed compounds, and anisotropic lipophilicity was related with statistically significant passive transcellular diffusion (r2 = 0.614, P < 0.001). Moreover, experimentally determined passive permeability, logPapp, was statistically significantly associated with both in silico–predicted absorption constant, ka (r2 = 0.7886, P < 0.001), and human intestinal absorption (HIA) in percentage (r2 = 0.484, P < 0.001), respectively. However, there was no statistically significant relationship between experimentally obtained permeability on non-cellular-based model and in silico–predicted Caco-2 permeability based on the predictions conducted on two different software. Based on the obtained results, anisotropic systems are promising surrogates for determining lipophilicity, except for compounds with acidic functional groups that are completely ionized under (pH = 7.4)