DEVELOPMENT AND OPTIMIZATION OF CARVEDILOL FORMULATION USING EXPERIMENTAL DESIGN

The aim of this paper was to develop and optimize the carvedilol tablets formulation using the full factorial design. The content of binder (PVP K30), content of disintegrant (crospovidone) and main compression force were used as the independent variables. Tablets were prepared by wet granulation. The percentage of released carvedilol from prepared formulation after 10 minutes was defined as the response. It has been found that formulation with the low content of binding agents (4.8%), high content of disintegrant (4.5%) and compression force of 50 N has the best profile of drug. The optimal formulation was defined based on implementation of pharmaceuticaltechnological tests (testing strength, friability, disintegrating, contents of drug substance, drug release profiles). The stability of the optimal formulation with carvedilol was estimated using the aging tests

Aquatic animal health education

Aquatic animals need veterinary care as any other animal species but sometimes this care is inadequately managed. The role of veterinarians in conventional farmed animal health prevention and control are undoubtedly some of the activities most commonly recognised to the veterinary profession. Although poultry, swine, beef, and other terrestrial animals have been historically considered as the main source for animal protein production, it is very important to highlight that nowadays, fisheries and aquaculture represent a substantial sources of animal protein for human consumption. Global fisheries have reached a non-sustainable breakpoint and, in this scenario, aquaculture emerges as the sustainable alternative for animal protein production for the future. Animal health and welfare, and particularly the control of impact of the diseases in finfish, crustacean and mollusc farming still represents a very important challenge for aquatic animal veterinarians. The ornamental fish sector is also a relevant area, and untapped resource for aquatic animal professionals. However, these needs are not followed by the same level of veterinary services required, indicating that there is still a lot of work to be done in this direction. Disease control and prevention, and aquatic animal health promotion across these different areas is a very challenging task for the future, and represent a tremendous source of opportunity for aquatic veterinarians.http://eafp.org/bulletin-archiveam2022Paraclinical Science

ANTIOXIDANT AND ANTIMICROBIAL ACTIVITIES OF THE ESSENTIAL OIL AND SOLVENT EXTRACTS OF MENTHA PULEGIUM L.

We report the total phenolic (TPC; expressed as gallic acid equivalents, GAE, per milligram of dry extract weight) and the total flavonoid contents (TFC; expressed as quercetin equivalents, QE, per milligram of dry extract weight) and antimicrobial and antioxidant activities of the essential oil and hexane, diethyl ether, ethyl acetate and methanol extracts of Mentha pulegium L. (Lamiaceae) collected in Serbia. The total phenolic content was in the range of 129.43-388.29 μg GAE/mg, while TFC ranged from 57.81 to 160.94 QE/mg; the highest TPC and TFC were found in the methanol extract. The antimicrobial activity (against five bacteria and two fungi species) of the essential oil and solvent extracts was assessed using disc-diffusion method. However, the studied samples demonstrated a poor antimicrobial potential. The antioxidant activity was screened using five different tests: 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid radical cation decolorization assay (ABTS), total reducing power (TRP), ferric reducing antioxidant power (FRAP) and cupric reducing antioxidant capacity assay (CUPRAC); the methanol extract showed the strongest antioxidant potential. The results of the different antioxidant assays were correlated mutually and with the total flavonoid and total phenolic contents (regression analysis and agglomerative hierarchical clustering). ANTIOKSIDANTNA I ANTIMIKROBNA AKTIVNOST ETARSKOG ULJA I EKSTRAKATA BILJNE VRSTE MENTHA PULEGIUM L.U ovom radu je određen sadržaj ukupnih fenola (TPC; izražen u ekvivalentima galne kiseline, GAE, po miligramu suvog biljnog ekstrakta) i ukupnih flavonoida (TPC; izražen u ekvivalentima kvarcetina, QE, po miligramu suvog biljnog ekstrakta), kao i antimikrobna i antioksidantna aktivnost etarskog ulja i heksanskog, dietil-etarskog, etil-acetatnog i metanolnog ekstrakta biljne vrste Mentha pulegium L. (Lamiaceae; populacija iz Srbije). Sadržaj ukupnih fenola analiziranih uzoraka se kretao u opsegu od 129,43 do 388,29 μg GAE/mg, dok je TFC bio u interval od 57,81 do 160,94 QE/mg; najviše vrednosti za TPC i TFC nađene su za metanolni ekstrakt. Antimikrobna aktivnost (prema pet bakterijskih i dva soja gljivica) etarskog ulja i ekstrakata je određena disk-difuzionom metodom. Proučavani uzorci su imali slabu antimikrobnu aktivnost. Antioksidantna aktivnost je ispitivana pomoću DPPH (2,2-difenil-1-pikrilhidrazil radikal), ABTS (2,2'-azino-bis(3-etilbenzotijazolin-6-sulfonska kiselina radikal katjon), TRP (ukupna redukciona sposobnost), FRAP (sposobnost redukcije feri-jona) i CUPRAC (sposobnost redukcije Cu(II)-jona) metodama; najviši antioksidantni potencijal je imao metanolni ekstrakt. Rezultati različitih metoda za određivanje antioksidantnog potencijala su korelisani međusobno, kao i sa sadržajem ukupnih fenola i flavonoida (regresiona analiza i aglomerativna hijerarhijska klaster analiza). HIGHLIGHTSThe essential oil and hexane, diethyl ether, ethyl acetate and methanol extracts of Mentha pulegium L. collected in Serbia were studied.Their total phenolic content was in the range of 129.43-388.29 μg GAE/mg, while total flavonoid content ranged from 57.81 to 160.94 QE/mg.Solvent extracts (SE) and essential oil of the studied M. pulegium population were poor antimicrobials.Antioxidant activities of SE were studied using five different methods.Differences between the previous and the present results suggest M. pulegium metabolic profile might be influenced by both genetic and environmental factors

Prevalence, characteristics and prognostic impact of aortic valve disease in patients with heart failure and reduced, mildly reduced, and preserved ejection fraction: An analysis of the ESC Heart Failure Long-Term Registry

AIMS To assess the prevalence, clinical characteristics, and outcomes of patients with heart failure (HF) with or without moderate to severe aortic valve disease (AVD) (aortic stenosis [AS], aortic regurgitation [AR], mixed AVD [MAVD]). METHODS AND RESULTS Data from the prospective ESC HFA EORP HF Long-Term Registry including both chronic and acute HF were analysed. Of 15 216 patients with HF (62.5% with reduced ejection fraction, HFrEF; 14.0% with mildly reduced ejection fraction, HFmrEF; 23.5% with preserved ejection fraction, HFpEF), 706 patients (4.6%) had AR, 648 (4.3%) AS and 234 (1.5%) MAVD. The prevalence of AS, AR and MAVD was 6%, 8%, and 3% in HFpEF, 6%, 3%, and 2% in HFmrEF and 4%, 3%, and 1% in HFrEF. The strongest associations were observed for age and HFpEF with AS, and for left ventricular end-diastolic diameter with AR. AS (adjusted hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.23-1.67), and MAVD (adjusted HR 1.37, 95% CI 1.07-1.74) but not AR (adjusted HR 1.13, 95% CI 0.96-1.33) were independently associated with the 12-month composite outcome of cardiovascular death and HF hospitalization. The associations between AS and the composite outcome were observed regardless of ejection fraction category. CONCLUSIONS In the ESC HFA EORP HF Long-Term Registry, one in 10 patients with HF had AVD, with AS and MAVD being especially common in HFpEF and AR being similarly distributed across all ejection fraction categories. AS and MAVD, but not AR, were independently associated with increased risk of in-hospital mortality and 12-month composite outcome, regardless of ejection fraction category

PTSD-8: A Short PTSD Inventory

Traumatic events pose great challenges on mental health services in scarcity of specialist trauma clinicians and services. Simple short screening instruments for detecting adverse psychological responses are needed. Several brief screening instruments have been developed. However, some are limited, especially in relation to reflecting the posttraumatic stress disorder (PTSD) diagnosis. Recently, several studies have challenged pre-existing ideas about PTSD’s latent structure. Factor analytic research currently supports two four factor models. One particular model contains a dysphoria factor which has been associated with depression and anxiety. The symptoms in this factor have been hailed as less specific to PTSD. The scope of this article is therefore to present a short screening instrument, based on this research; Posttraumatic Stress Disorder (PTSD) – 8 items. The PTSD-8 is shown to have good psychometric properties in three independent samples of whiplash patients (n=1710), rape victims (n=305), and disaster victims (n=516). Good test-rest reliability is also shown in a pilot study of young adults from families with alcohol problems (n=56)

Zebrafish Kidney Phagocytes Utilize Macropinocytosis and Ca2+-Dependent Endocytic Mechanisms

Background: The innate immune response constitutes the first line of defense against invading pathogens and consists of a variety of immune defense mechanisms including active endocytosis by macrophages and granulocytes. Endocytosis can be used as a reliable measure of selective and non-selective mechanisms of antigen uptake in the early phase of an immune response. Numerous assays have been developed to measure this response in a variety of mammalian and fish species. The small size of the zebrafish has prevented the large-scale collection of monocytes/macrophages and granulocytes for these endocytic assays. Methodology/Principal Findings: Pooled zebrafish kidney hematopoietic tissues were used as a source of phagocytic cells for flow-cytometry based endocytic assays. FITC-Dextran, Lucifer Yellow and FITC-Edwardsiella ictaluri were used to evaluate selective and non-selective mechanisms of uptake in zebrafish phagocytes. Conclusions/Significance: Zebrafish kidney phagocytes characterized as monocytes/macrophages, neutrophils and lymphocytes utilize macropinocytosis and Ca 2+-dependant endocytosis mechanisms of antigen uptake. These cells do not appear to utilize a mannose receptor. Heat-killed Edwardsiella ictaluri induces cytoskeletal interactions for internalization in zebrafish kidney monocytes/macrophages and granulocytes. The proposed method is easy to implement and should prove especially useful in immunological, toxicological and epidemiological research

Association between loop diuretic dose changes and outcomes in chronic heart failure: observations from the ESC-EORP Heart Failure Long-Term Registry

[Abstract] Aims. Guidelines recommend down-titration of loop diuretics (LD) once euvolaemia is achieved. In outpatients with heart failure (HF), we investigated LD dose changes in daily cardiology practice, agreement with guideline recommendations, predictors of successful LD down-titration and association between dose changes and outcomes. Methods and results. We included 8130 HF patients from the ESC-EORP Heart Failure Long-Term Registry. Among patients who had dose decreased, successful decrease was defined as the decrease not followed by death, HF hospitalization, New York Heart Association class deterioration, or subsequent increase in LD dose. Mean age was 66±13 years, 71% men, 62% HF with reduced ejection fraction, 19% HF with mid-range ejection fraction, 19% HF with preserved ejection fraction. Median [interquartile range (IQR)] LD dose was 40 (25–80) mg. LD dose was increased in 16%, decreased in 8.3% and unchanged in 76%. Median (IQR) follow-up was 372 (363–419) days. Diuretic dose increase (vs. no change) was associated with HF death [hazard ratio (HR) 1.53, 95% confidence interval (CI) 1.12–2.08; P = 0.008] and nominally with cardiovascular death (HR 1.25, 95% CI 0.96–1.63; P = 0.103). Decrease of diuretic dose (vs. no change) was associated with nominally lower HF (HR 0.59, 95% CI 0.33–1.07; P = 0.083) and cardiovascular mortality (HR 0.62 95% CI 0.38–1.00; P = 0.052). Among patients who had LD dose decreased, systolic blood pressure [odds ratio (OR) 1.11 per 10 mmHg increase, 95% CI 1.01–1.22; P = 0.032], and absence of (i) sleep apnoea (OR 0.24, 95% CI 0.09–0.69; P = 0.008), (ii) peripheral congestion (OR 0.48, 95% CI 0.29–0.80; P = 0.005), and (iii) moderate/severe mitral regurgitation (OR 0.57, 95% CI 0.37–0.87; P = 0.008) were independently associated with successful decrease. Conclusion. Diuretic dose was unchanged in 76% and decreased in 8.3% of outpatients with chronic HF. LD dose increase was associated with worse outcomes, while the LD dose decrease group showed a trend for better outcomes compared with the no-change group. Higher systolic blood pressure, and absence of (i) sleep apnoea, (ii) peripheral congestion, and (iii) moderate/severe mitral regurgitation were independently associated with successful dose decrease

Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry

Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P\ua0 64 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P\ua0=\ua00.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P\ua075 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF 6445%