Insomnia is an important problem in dialysis patients. A greater prevalence of insomnia in chronic kidney disease compared with non‐renal patients suggests a role for uraemic toxins in contributing to insomnia. The aim of this study was to examine if dialysis modality and membrane permeability is associated with the frequency and severity of insomnia in haemodialysis patients.

Introduction: The weak anticonvulsant activity of the analgesic flupirtine led to the creation of ezogabine; an analogue which demonstrated both stronger antiepileptic activity and weaker analgesic effects. It's use as an anticonvulsant has been particularly effective in treating patients who have therapy-resistant epilepsy. Ezogabine binds to the KCNQ potassium channel, thereby decreasing the membrane potential threshold for its activation and increasing the probability of its maximum opening. Areas covered: This drug discovery case history provides an overview of the history of the anticonvulsant, ezogabine, and presents relevant information pertaining to its discovery and preclinical development. The article helps explain the methods of discovery through the explanation of ezogabine's mechanism of action. Further, the authors also highlight the drugs clinical development and its postlaunch developments. Expert opinion: More intense investment in research on the molecular mechanism of action early in the preclinical development of a drug could allow for the more suitable planning of preclinical studies and for the early discovery of specific, but important drug toxicities. This investment would make transitioning from the preclinical to the clinical phase easier and could result in better planning for what will be more productive clinical studies.

Introduction Pseudomonas aeruginosa is well-known cause of hospital infections with high morbidity and mortality rates [1]. According to the National Nosocomial Infections Surveillance System (NNISS), P. aeruginosa is responsible for approximately 8% of all hospital infections. It was the most frequent cause of ventilator-associated pneumonias (VAP), the fourthrated on the list of causes of hospital urinary infections, and fifth cause of surgical site infections according to frequency of occurence (2). Infections caused by P. aeruginosa are difficult to control and treat due to its high rate of resistance to antibiotics and to the limited number of available antibiotics with efficacy against P. aeruginosa. During the last decade, an increase in resistance to imipenem and meropenem was observed among many strains of Gram-negative bacteria, and especially among isolates of P. aeruginosa [3,4,5]. Numerous studies have also shown that carbapenem-resistant P. aeruginosa (CRPA) is frequently simultaneously resistant to other antipseudomonal antibiotics, making the treatment very difficult [6]. A number of risk factors for the emergence of CRPA-caused hospital infections was identified, including spending time in an intensive care unit and/or prior use of certain antibiotics [7,8,9,10]; however, for the majority of factors, the strength of the association was either low or equivocal. Sound knowledge of the risk factors and quantification of their influence on hospital infections are important for proper prevention and treatment of the CRPA-caused nosocomial infections. The aim of this study was to identify risk factors associated with the CRPA-caused hospital infections.

Communication process gives to physician necessary information for establishing diagnosis and prescribing therapy, and helps to a patient to gain confidence in his doctor and the prescribed treatment. The communication between doctor and his patient is enhanced by the following: openness and conscientiousness of the physician, serious approach to the patient, participation of the patient in decision-making, advanced age and higher education of the patient. On the other hand, communication is less efficient if the doctor has longer employment status, if he/her avoids disclosure of all relevant information to the patient, if he/her is emotionally separated from the patient, if the time for an encounter is limited, if the patient is passive and with unrealistic expectations, and if the doctor is expressing himself/herself unclearly.   In order to improve communication with patients, doctors should follow these recommendations: keeping eye contact with a patient, releasing tension from his/her body language, taking detailed patient history with active listening and without interrupting of a patient, speaking clearly and slowly, using language understandable to a patient, treating patients with equality, disclosing all relevant information to the patient and sharing decision-making with the patient. Adequate communication between doctor and patient always brings better treatment outcomes.

Urinary tract infections are common bacterial diseases and also a frequent reason for prescribing antibiotics. Knowledge about the type of pathogens and their resistance patterns may help the clinician to choose the correct treatment. In this study, the prevalence and the resistance pattern of the main bacteria responsible for urinary tract infections оf hospitalized patients in Clinical centar Kragujevac was evaluated throughout a tree-year period. Cross-sectional study in the hospital settings was conducted and urine samples were collected from 662 patients with urinary tract infections and tested using standard procedures. The disk-diffusion method on Mueller-Hinton agar according to Clinical and Laboratory Standards Institute guidelines (CLSI) was performed for assessment of antimicrobial susceptibility. The most frequently isolated pathogen were Klebsiella spp. (219 isolates, i.e. 33,1%), Proteus mirabilis (107 isolates, i.e. 16,2%), Enterobacter (86 isolates, i.e. 13%), Escherichia coli (82 isolates, i.e. 12,4%), Pseudomonas aeruginosa (70 isolates, i.e. 10,6%), Enterococcus spp (39 isolates, i.e. 5,9% ) and Proteus vulgaris (38 isolates, i.e. 5,7%). Group of patients older than 65 years was the largest one 426 (64,4%). Gram negative bacteria showed the highest degree of resistance (92.3% - 100%) to penicillins (ampicillin, amoxicillin, amoxicillin + clavulanic acid) and third-generation cephalosporins (cefotaxime, ceftriaxone and ceftazidime) (88.3% - 98, 4%), while Gram positive Enterococcus spp showed the highest degree of resistance to aminoglycosides (gentamicin and amikacin) (96.8% - 100%) and fluoroquinolone ciprofliksacin (100%). The lowest resistance rate of the studied Gram negative pathogens was to carbapenems (imipenem and meropenem) and piperacillin / tazobactam (6.9% - 35.5%), while the lowest level of resistance of gram positive Enterococcus spp was found to glycopeptide antibiotics (vancomycin and teicoplanin) (3.0% - 3.3%). When choosing antibiotics, the pharmacokinetics and pharmacodynamics, renal and liver function, adverse reactions with other drugs, as well as the results of susceptibility testing should be taken into consideration. According to our data, empiric treatment for Klebsiella spp, Proteus mirabilis, Enterobacter, Escherichia coli, Pseudomonas aeruginosa and Proteus vulgaris should include carbapenems or piperacillin / tazobactam, and when it comes to Enterococcus spp , glycopeptide antibiotics are appropriate choice.

The aim of this study was to derive population pharmacokinetic (PK) model for clearance (CL) of carvedilol in adult patients with chronic heart failure (CHF). Medication and demographic data were obtained from 52 Caucasian patients with CHF taking carvedilol. Population PK analysis was performed by nonlinear mixed-effects modeling (NONMEM) to estimate and identify different factors that could affect carvedilol CL. A total of 55 plasma concentrations were collected from 52 patients with mean age of 63.02 ± 11.95 years and total body weight (TBW) of 77.96 ± 13.46 kg. Total daily doses of carvedilol in the target population had wide range of variability (6.25-50 mg), followed by high variability of drug plasma concentrations (1-59.07 ng/mL). The typical mean value for carvedilol CL, estimated by the base model, in the target population was 43.8 L/h. The TBW, concomitant therapy with digoxin, and tobacco using were determinants of a derived population model. The final regression model for the CL of carvedilol is: [Formula: see text] Our results suggest that the TBW, concomitant therapy with digoxin, and tobacco using are the main subjects of carvedilol PK variability.

Normal 0 false false false MicrosoftInternetExplorer4 Helianthus tuberosus L. ( Jerusalem artichoke) belongs to the Asteraceae family , genus Heliathus . The plant is growing in Serbia and Romania, as native species. The most valuable constituent is inulin, which together with other constituents forms unique content of such plant material. Inulin has effect on reducing the risk of cardiovascular diseases; it acts beneficially in different gastrointestinal conditions possessing a prebiotic role, which showed to be important in prevention and/or alleviation of the osteoporosis progress. The aim of this study was comparison of the chemical composition of Heliantus tuberosus L . tubers growing at two different geographic area on Balcan peninsula, namely in Serbia and in Romania. We have determined content of eight main components in both herbal samples: total proteins, flavonoids, polyphenolic carboxylic acids, reducing sugars, total carbohydrates, antioxidant, inulin and ascorbic acid and calculated a caloric value of heral samples. The level of all investigated compounds, except of the total carbohydrates and antioxidant, was slightly higher in the plant growing in Romania than in the plant growing in Serbia. Since the differences in the content of both materials are very small, we propose that both materials could be considered as suitable raw plant material for further processing. The caloric value of plant growing in Serbia was found to be slightly higher than caloric value of the one growing in Romania. The both herbal samples are good source of inulin and represents valuable raw plant material for further processing.

Potentilla reptans L. belongs to the least studied of the plants from Rosaceae family, Potentilla genus. There are no data on cytotoxicity of P. reptans extracts, though traditionaly it was used as antiinflammatory and antiinfective. The aim of these studies was to investigate potential antitumor activity of aqueous extracts (rhizome and aerial parts) of P. reptans on 4T1 mouse breast cancer cell line. _Aqueous extracts of rhizome and aerial parts of P. reptans were tested for cytotoxicity by the MTT colorimetric assay on 4T1 cancer cell line in concentration range 100-800 microg/mL. Aqueous extracts of P. reptans rhizome and aerial parts show concentration dependent cytotoxic effect in the range of tested concentrations. ICE50 value of P. reptans rhizome extract was 280.51 +/- 1.16 microg/mL. IC50 value of P. reptans aerial parts extract was 310.79 +/- 1.22 microg/mL. The significant difference in cytotoxicity among tested concentrations was observed. Aqueous extracts of P. reptans rhizome and aerial parts demonstrated weak cytotoxic activity on 4T1 mouse breast cancer cell line, which is in correlation with current cytotoxicity data for aqueous herbal extracts. Rhizome extract of P. reptans has slightly higher antitumor activity than aerial parts extract. The results represent the first report on cytotoxicity for this plant and further research on human cell lines is indicated.

According to various authors, thyroid disorders like Hashimoto's thyroiditis (HT), diffuse goiter or multinodular goiter, Graves' disease, medullary or papillary carcinoma could be found in a number of patients with primary hyperparathyroidism (PHPT). This association is more common in elderly women. Neck irradiation, lithium treatment and elevated TSH levels have been suggested as some of the possible causes of this co-existance. The aim of this study was to investigate and determine the prevalence of patients having both HT and PHPT, and the possible relation between these two diseases. We conducted a prospective study during three and a half years. This study included 45,231 patients, which were referred by their general practitioner or endocrinologist, under suspicion of having thyroid and/or parathyroid disease. In these patients we measured serum levels of the following parameters: anti-thyroid peroxidase antibodies (antiTPO-Ab), anti-thyroglobulin antibodies (Tg-Ab), anti-TSH-receptor antibodies (TSHR-Ab), thyroid-stimulating hormone (TSH), parathyroid hormone (PTH) and calcium (Ca). In 2,267 of these 45,231 patients (5.01%) we noticed elevated antiTPO-Ab (3542±3407IU/mL), with statistical significant difference from normal values (normal range 0-70IU/mL), P<0.05, and normal levels of other antithyroid antibodies (Tg-Ab, TSHR-Ab). All patients with elevated antiTPO-Ab were assumed to have HT. Within this group, 43 patients (1.89%) also had elevated serum levels of PTH (112.4±33.2pg/mL, normal range 8-76pg/mL) as well as elevated serum levels of calcium (2.92±0.06mmol/L, normal range 2.2-2.65mmol/L). These laboratory findings, accompanied with clinical symptoms, satisfied the criteria for PHPT. The mean age in this subgroup was 60.5±12.2 years. All 2,267 patients had normal or slightly elevated TSH levels. In conclusion, although the reported rate of prevalence of PHPT in the general population is about 0.3%, our results indicated a 1.89% occurrence of PHPT in 2267 patients with HT in central Serbia. This may be due to the autoimmune inflammatory process in HT supporting PHPT to PTH or calcium supporting HT or to common genetical predisposition of both entities.

INTRODUCTION Almost all individual antipsychotics are classified into the intermediate pregnancy risk category as no or limited data exist about human pregnancy outcomes. We presented the case of zuclopenthixol decanoate using in two successive pregnancies of the same woman, which had not been published in the available peer-reviewed literature. CASE REPORT A middle-age female subject who suffered from schizophrenia received zuclopenthixol decanoate injection during her two consecutive pregnancies. About four and a half months before diagnosis of the first pregnancy (to approximately 3.5 years after psychosis emergence), zuclopenthixol decanoate (400 mg every other week, im injection) was introduced to the treatment protocol (due to previous non-compliance with haloperidol and risperidone). A significant clinical improvement was achieved and the dose during pregnancy was reduced to 200 mg once monthly and maintained to date. In both pregnancies the women gave birth to healthy girls who have been developing normally until now, at their ages of 6 months and of 3.5 years. During pregnancy and after giving birth to children the mothers' psychiatric status and her social functioning were significantly improved and are still stable. Close monitoring of the mother's health, a multidisciplinary approach to both her treatment and the monitoring of pregnancies as well as the complete compliance with the prescribed drug protocol were likely to be crucial for the therapeutic success. CONCLUSION A favorable outcome of the present case suggests that the zuclopenthixol decanoate is a rational therapeutic option for pregnant women suffering from psychosis when the expected benefit exceed the potential risk, but a definitive evidence for its safety requires large, controlled studies.

This article reviews a population pharmacokinetics studies conducted during the past few years in Serbia. Studies have included three the most frequently used antiepileptic drugs (valproate, carbamazepine and lamotrigine) and different populations of epileptic patients: children, adults and heterogeneous population composed of both children and adults. The review compares obtained values of population pharmacokinetic models of clearance of these drugs, and factors that are significantly determined, making brief comments on the results of other authors on the same topic. Individualization of drug dosage is the basis of rational therapy, and factors of variability will always be subject of scientific research.