Gender-specific differences in hemodialysis patients: a multicenter longitudinal study from Serbia.

PURPOSE: The study was undertaken with the aim to determine gender-specific differences in incident hemodialysis (HD) patient and their changes over time. METHODS: The retrospective longitudinal closed cohort study involved 441 incident patients starting HD in 2014 and followed for 1-59 (median 43, IQR 40) months. Demographic, clinical data, treatment characteristics, laboratory findings and outcome were abstracted from the patients' medical records. RESULTS: The relative number of males on HD was about twice that of females throughout the five years investigated. At the beginning of the study, no significant differences were found in the main demographic and clinical characteristics except that diabetes was more often the underlying disease in men than in women. Systolic blood pressure decreased over time significantly more in females than in males. Throughout the study spKt/V was significantly higher in females than in males, but it increased in patients of both genders. There were no gender differences for comorbidities, vascular access and the majority of laboratory findings except for higher serum levels of creatinine and CRP in men than in women. Relatively more females were treated with erythropoiesis stimulating agents and phosphate binders than males. Age and malignancy were selected as significant predictors of mortality for both genders, and, in addition, polycystic kidney disease, serum level of albumin and CRP for men, but spKt/V for women. CONCLUSION: Some significant gender differences were observed throughout, while others appeared during the study but none of them were due to gender inequalities in the applied treatment.

Design of biopolymer carriers enriched with natural emulsifiers for improved controlled release of thyme essential oil.

This work aims to characterize a novel system for thyme essential oil delivery based on the combination of natural emulsifiers (soy protein and soy lecithin) and alginate, produced using the extrusion technique. The formulations are optimized concerning alginate and soy protein concentrations (both 1 to 1.5 wt.%), and consequently lecithin amount, in order to achieve spherical beads in the range 2.0 to 2.3 mm and 1.2 to 1.4 mm, wet and dry, respectively. Fourier-transform infrared analysis was performed, proving that there are interactions between all components. Lecithin-soy protein synergistic combination improved entrapment efficiency of total polyphenols (for nearly 12%) and decreased thymol release in a simulated gastric solution for nearly 35%, in comparison with beads without lecithin. The addition of lecithin enhances the thermal properties of the polysaccharide-protein systems at 50 °C after 3 hr of heating. The mechanical stability of the biopolymer carriers is improved with lecithin addition and the elastic modulus varied from 80.06 to 123.7 kPa, depending on the formulation. Alginate/soy protein/lecithin are effective carriers for the encapsulation, protection, and controlled release of thyme essential oil. PRACTICAL APPLICATION: There is unfortunately growing human resistance to antibiotics. This work offers a novel system for effective protection and controlled release of thyme essential oil in the small intestine. The mechanical and thermal properties of the carrier were estimated as they indicate how the beads will be able to resist stress during their incorporation into food (i.e. cookies-mixing, baking). The proposed approach offers ''green advantage'' as arises from all-natural materials.

Effect of gentisic acid on the structural-functional properties of liposomes incorporating ß-sitosterol.

Multifunctional liposomes incorporating ß-sitosterol were developed for delivery of gentisic acid (GA). The interactions of both compounds with phospholipid bilayer were interpreted viaeffects of different ß-sitosterol content (0, 20 and 50 mol %) and different gentisic acid to lipid ratio (nGA/nlip from 10-5 to 1) on membrane fluidity and thermotropic properties. Multilamellar vesicles of phosphatidylcholines (with size range between 1350 and 1900 nm) effectively encapsulated GA (54%) when nGA/nlip was higher than 0.01. Suppression of lipid peroxidation was directly related to concentration of GA. The resistance to diffusion of gentisic acid from liposomes increased for ˜50% in samples incorporating 50 mol % ß-sitosterol compared to sterol-free liposomes. Finally, simulated in vitro gastrointestinal conditions showed that the release was mainly affected by low pH of simulated gastric fluid and the presence of cholates in simulated intestinal fluid, rather than by enzymes activity.

Alginate/soy protein system for essential oil encapsulation with intestinal delivery.

Preparation of alginate-soy protein isolate (AL/SPI) complex beads containing essential oil of thyme was carried out by emulsification of thyme oil in aqueous sodium alginate solution blended with SPI solution, followed by atomization via electrostatic extrusion and gelification with calcium ions. The process parameters were optimized by variation of the alginate (1-2.5 wt.%) and SPI (0-1.5 wt.%) concentrations. Dry alginate-SPI particles exhibited wrinkle surface while shape distortion of hydrogel beads occurred with ≥1.5 wt.% alginate concentration, whereas SPI induced reduction of the particle size. Encapsulation efficiency of 72-80 % based on total polyphenols was achieved. In SGF the samples exhibited oil release of 42-55 % (due to matrix shrinkage and proteins degradation by pepsin activity), while the rest was delivered in SIF within 2.5 h simultaneously with swelling and degradation of the matrix.

Calcium-Alginate-Inulin Microbeads as Carriers for Aqueous Carqueja Extract.

Carqueja (Pterospartum tridentatum) is an endemic species and various bioactive compounds have been identified in its aqueous extract. The aim of this study was to protect the natural antioxidants from the aqueous extract of carqueja by encapsulation in Ca-alginate microbeads and Ca-alginate microbeads containing 10% and 20% (w/v) of inulin. The microbeads produced by electrostatic extrusion technique had an average diameter from 625 µm to 830 µm depending on the portion of inulin. The sphericity factor of the hydrogel microbeads had values between 0.014 and 0.026, while freeze dried microbeads had irregular shape, especially those with no excipient. The reduction in microbeads size after freeze drying process (expressed as shrinkage factor) ranged from 0.338 (alginate microbeads with 20% (w/v) of inulin) to 0.523 (plain alginate microbeads). The expressed radical scavenging activity against ABTS and DPPH radicals was found to be between 30% and 40% for encapsulated extract, while the fresh extract showed around 47% and 57% of radical scavenging activity for ABTS and DPPH radicals, respectively. The correlation between antioxidant activity and the total phenolic content were found to be positive (in both assay methods, DPPH and ABTS), which indicate that the addition of inulin didn't have influence on antioxidant activity. The presence of inulin reduced stiffness of the hydrogel, and protected bead structure from collapse upon freeze-drying. Alginate-inulin beads are envisaged to be used for delivery of aqueous P. tridentatum extract in functional food products.

Chitosan crosslinked microparticles with encapsulated polyphenols: Water sorption and release properties.

Chitosan-glutaraldehyde microparticles were produced by emulsion crosslinking method to be used as drug delivery system for polyphenols from Thymus serpyllum L. aqueous extract. The effect of preparation conditions, chitosan concentration (1.5-3% w/v), and glutaraldehyde/chitosan (GA/Ch) mass ratio (0.15-1.20) on water and polyphenols transport properties was investigated. Swelling ratio of dry particles (68-230 µm) in water ranged from 280% to 530%, depending on the formulation. The decrease in swelling was observed with increased GA/Ch mass ratio (i.e. crosslinking degree) at the same chitosan concentration, or with increased chitosan concentration at the same GA/Ch mass ratio. The increase in GA/Ch mass ratio was also manifested by increased particle compactness i.e. decreased size and reduced surface roughness. The sorption capacity for polyphenols seems to be a complex interplay of swelling behaviour and interactions chitosan-glutaraldehyde-polyphenols identified by Fourier transmission infrared analysis. An increase in crystallinity of chitosan was observed upon crosslinking with glutaraldehyde and encapsulation of polyphenols, as observed by X-ray diffraction analysis. The results obtained from release kinetics of selected polyphenolic compounds (caffeic acid, rosmarinic acid, total flavonoids, and total phenol content) showed that polyphenols were released at a lower amount (2-4 times) in water, but more rapidly (45-120 min) in comparison with the release in gastric followed by intestinal simulated fluid (SGF-SIF) (120-240 min). The experimental results of the time-dependent swelling in water and polyphenols release in both, water and SGF-SIF, were analyzed with several mathematical models. The results depicted Fickian diffusion as the water transport mechanism. In the case of polyphenols, only empirical Weibull model could be suggested for describing release kinetics.

Compliance with guidelines and predictors of mortality in hemodialysis. Learning from Serbia patients.

OBJECTIVES: The aims of the study were to determine the percentage of patients on regular hemodialysis (HD) in Serbia failing to meet KDOQI guidelines targets and find out factors associated with the risk of time to death and the association between guidelines adherence and patient outcome. METHODS: A cohort of 2153 patients on regular HD in 24 centers (55.7% of overall HD population) in Serbia were followed from January 2010 to December 2012. The percentage of patients failing to meet KDOQI guidelines targets of dialysis dose (Kt/V>1.2), hemoglobin (>110g/L), serum phosphorus (1.1-1.8mmol/L), calcium (2.1-2.4mmol/L) and iPTH (150-300pg/mL) was determined. Cox proportional hazards analysis was used to select variables significantly associated with the risk of time to death. RESULTS: The patients were on regular HD for 5.3±5.3 years, dialyzed 11.8±1.9h/week. Kt/V<1.2 had 42.4% of patients, hemoglobin <110g/L had 66.1%, s-phosphorus <1.1mmol/L had 21.7% and >1.8mmol/L 28.6%, s-calcium <2.1mmol/L had 11.7% and >2.4mmol/L 25.3%, iPTH <150pg/mL had 40% and >300pg/mL 39.7% of patients. Using Cox model (adjustment for patient age, gender, duration of HD treatment) age, duration of HD treatment, hemoglobin, iPTH and diabetic nephropathy were selected as significant independent predictors of time to death. When targets of five examined parameters were included in Cox model, target for KtV, hemoglobin and iPTH were found to be significant independent predictors of time to death. CONCLUSION: Substantial proportion of patients examined failed to meet KDOQI guidelines targets. The relative risk of time to death was associated with being outside the targets for Kt/V, hemoglobin and iPTH.

Depression and quality of sleep in maintenance hemodialysis patients.

INTRODUCTION: Sleep disorders and psychological disturbances are common in end-stage renal disease (ESRD) patients. However, despite their frequency and importance, such conditions often go unnoticed, since all patients do not clearly manifest fully expressed symptoms. OBJECTIVE: This study aimed to determine the prevalence of depression and poor sleep quality and to examine the association between these disorders and demographic, clinical and treatment-related characteristics of ESRD patients on hemodialysis (HD). METHODS: The study included 222 patients (132 men and 90 women), mean age 57.3 +/- 11.9 years, from 3 HD centers in Central Serbia, which provided us with biochemical parameters and demographic data. Sleep quality and depression were assessed using the Pittsburgh Sleep Quality Index (PSQI) and Beck Depression Inventory (BDI), respectively. RESULTS: The average BDI was 16.1 +/- 11.3. Depressed patients were significantly older (p=0.041), had a significantly lower dialysis adequacy (p=0.027) and a significantly worse quality of sleep (p < 0.001), while they did not show significant difference as regarding sex, employment, marital status, comorbidities, dialysis type, dialysis vintage, shift and laboratory parameters.The average PSQI was 7.8 +/- 4.5 and 64.2% of patients were poor sleepers. Poor sleepers were significantly older (p = 0.002), they were more often females (p = 0.027) and had a significantly higher BDI (p < 0.001), while other investigated variables were. not correlated with sleep quality. A statistically significant positive correlation was found between BDI and PSQI (r = 0.604; p < 0.001). CONCLUSION: Depression and poor sleep quality are frequent and interrelated among HD patients.

Chitosan microbeads for encapsulation of thyme (Thymus serpyllum L.) polyphenols.

In this work chitosan microbeads were prepared by emulsion technique and loaded with thyme polyphenols by diffusion from an external aqueous solution of Thymus serpyllum L. The effects of concentrations of chitosan (1.5-3% (w/v)) and GA (glutaraldehyde) (0.1-0.4% (v/v)), as a crosslinking agent on the main properties of microbeads were assessed. The obtained microgel beads from ∼ 220 to ∼ 790 µm in diameter were exposed to controlled drying process at air (at 37 °C) after which they contracted to irregular shapes (∼ 70-230 µm). The loading of dried microbeads with polyphenols was achieved by swelling in the acidic medium. The swelling rate of microbeads decreased with the increase in GA concentration. Upon this rehydration, thyme polyphenols were effectively encapsulated (active load of 66-114 mg GAE g(beads)(-1)) and the microbeads recovered a spherical shape. Both, the increase in the amount of the crosslinking agent and the presence of polyphenols, contributed to a more pronounced surface roughness of microbeads. The release of encapsulated polyphenols in simulated gastrointestinal fluids was prolonged to 3h.

[Renal replacement therapy in adult dominant polycystic kidney disease--multicentre study].

INTRODUCTION: Adult polycystic kidney disease (APKD) is the most common hereditary kidney disease in humans. The course of the disease is accompanied by numerous complications. OBJECTIVE The aim was to assess the prevalence, clinical course and outcome of adult dominant polycystic kidney disease (ADPKD) patients on renal replacement therapy. METHOD: Medical data on 700 haemodialyzed (HD) and 500 transplanted patients treated in 10 Serbian centres from 1996 to 2000 were retrospectively analyzed. While ADPKD patients accounted for 13% of HD patients in Serbia in 2000, in the period between 1996 and 2000, the percent of patients with ADPKD in the population of patients starting HD in 8 examined centres changed from 13.5% to 6.9%. RESULTS: The total number of 180 ADPKD patients on HD was analyzed (96 males; aged 55 years at HD onset). Their HD lasted between 1 and 22 years: males started HD 1.3 years earlier and spent on HD 1.1 years less than females. In 53% of HD patients one or more family members had ADPKD but the cause of death was unknown for many family members. Hypertension was present in 75% of ADPKD patients, anaemia in 37% and other organ involvement (usually liver) was found in 53 patients. Fifty patients experienced AV fistula thrombosis and a vascular prosthesis had to be used in 9 of them. A hundred and two HD patients died (aged between 38 and 78 years, on HD for 5.3 years). The causes of death were stroke (19.6%), cardiovascular diseases (29%), infections, while 5% of patients died with the picture of acute abdomen. Among 500 transplanted patients, there were 20 patients with ADPKD (11 males, ages between 35 and 56 years at the time of transplantation) and 14 of them received graft from cadaver donor. Uni- or bilateral nephrectomy was done in 4 patients in the pretransplant preparation, and in another two early after transplantation due to urinary infection. Three patients restarted HD in the first 3 months after transplantation due to acute tubular necrosis and 10 patients died 56.5 months after the transplantation. The known causes of death were cardiovascular disease (3 patients), severe gastrointestinal bleeding (2 patients), infection (2 patients) and cancer (2 patients). CONCLUSION: The obtained results showed that it was possible to provide a favourable outcome of patients with APBB on renal replacement therapy in spite of numerous complications.