Terken Baydar

Polypharmacy in the elderly: a multicenter study.

OBJECTIVE The aim of this study was to evaluate the polypharmacy issue and its correlations with socioeconomic variables in Turkish elderly patients. DESIGN Cross-sectional SETTING Outpatient clinics of the medical schools, departments of physical medicine and rehabilitation from 12 provinces. PARTICIPANTS A total of 1430 elderly in different geographical regions of Turkey during January 2007 to January 2008 were included. MEASUREMENTS Patients were interviewed using a questionnaire that included demographic characteristics, current medical diagnosis, and pharmaceuticals that are used by elderly. Demographical parameters were gender, age, marital status, number of children, level of education, province, and status of retirement. RESULTS The mean number of drugs was found to be higher in the females. There was a significant difference among age groups, marital status groups, and the number of children categories. The distribution of the number of drugs among education levels did not differ significantly, whereas the distribution of the number of drugs between the status of retirement and presence of chronic disease differed significantly. CONCLUSIONS Polypharmacy is correlated with various factors including age, sex, marital status, number of children, status of retirement, and presence of chronic medical conditions but not educational status in our study group.

Toxicity of acrylamide and evaluation of its exposure in baby foods.

Contaminants are a vast subject area of food safety and quality and can be present in our food chain from raw materials to finished products. Acrylamide, an α,β-unsaturated (conjugated) reactive molecule, can be detected as a contaminant in several foodstuffs including baby foods and infant formulas. It is anticipated that children will generally have intakes that are two to three times those of adults when expressed on a body-weight basis. Though exposure to acrylamide is inevitable, it is necessary to protect infant and children from high exposure. The present review focuses on the several adverse health effects of acrylamide including mutagenicity, genotoxicity, carcinogenicity, neurotoxicity and reproductive toxicity, and the possible outcomes of childhood exposure from baby foods and infant formulas.

Accumulation of aluminum in rat brain: Does it lead to behavioral and electrophysiological changes?

The present study was undertaken to examine possible aluminum (Al) accumulation in the brain of rats and to investigate whether subchronic exposure to the metal leads to behavioral and neurophysiological changes in both treated and control groups. Each of the groups consisted of 10 animals. Aluminum chloride (AlCl3) at a low (50 mg/kg/d) or high (200 mg/kg/d) dose was applied to male Wistar rats by gavage for 8 wk. Al-free water by gavage was given to the control group throughout the experiment. Behavioral effects were evaluated by open-field (OF) motor activity and by acoustic startle response (ASR). Electrophysiological examination was done by recording spontaneous activity and sensory-evoked potentials from the visual, somatosensory, as well as auditory cortex. The Al content of each whole brain was determined by electrothermal atomic absorption spectrophotometry. Subchronic Al exposure slightly caused some changes in the evoked potentials and electrocorticograms and in the OF and ASR performance, but these results were not statistically significant. The brain Al levels of the control and the low and high dose of Al-exposed groups were measured as 0.717±0.208 µg/g (wet weight), 0.963±0.491 µg/g (wet weight) and 1.816±1.157 µg/g (wet weight), respectively.

Neopterin as a prognostic biomarker in intensive care unit patients

PURPOSE The present study was undertaken to evaluate urinary neopterin in intensive care unit patients. MATERIALS AND METHODS Urinary neopterin levels were determined in systemic inflammatory response syndrome (n = 10), sepsis (n = 18), septic shock (n = 9), and multiple organ dysfunction syndrome (n = 5). It was tested whether neopterin is a differential parameter among the patient groups. Furthermore, the results were also evaluated by comparing with a healthy control group (n = 30), and the relationship between neopterin and mortality or Acute Physiology and Chronic Health Evaluation II scores were investigated. RESULTS Neopterin levels of the control group and patients were detected as 111 +/- 11 and 3850 +/- 1081 mumol/mol creatinine, respectively (P < .05). It was significantly increased in the sepsis and septic shock groups compared to the systemic inflammatory response syndrome group (P < .05). Neopterin levels were significantly higher in the patients with mortality and lower Acute Physiology and Chronic Health Evaluation II scores. CONCLUSION This study showed that monitoring of urinary neopterin profile can be used in intensive care units to show the degree and prognosis of the disease.

Immunomodulatory effects of Turkish propolis: changes in neopterin release and tryptophan degradation.

In most of the diseases which are considered to benefit from propolis, cellular immune reaction is activated, neopterin levels in body fluids are increased and enhanced tryptophan degradation is observed. In this study, the immunomodulatory effects of six Turkish propolis samples were evaluated by using the in vitro model of peripheral blood mononuclear cells (PBMC). Concentrations of neopterin, tryptophan, kynurenine and pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were determined and also the viability of the cells was checked with trypan blue and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] test. In PBMC treated with mitogen phytohaemagglutinin, neopterin production and tryptophan degradation by enzyme indoleamine 2,3-dioxygenase (IDO) as well as release of cytokines was significantly enhanced and upon treatment with propolis extracts all these effects were dose-dependently suppressed. Results show an immunomodulatory effect of propolis extracts which includes down-regulation of IDO activity. IDO enzyme is considered to play an important role in the development of immunodeficiency and neuropsychiatric symptoms in patient with chronic inflammation. The suppression of tryptophan degradation by propolis extracts may therefore be related with some of its beneficial health properties in humans.

Evaluation of the protective effect of ascorbic acid on nitrite- and nitrosamine-induced cytotoxicity and genotoxicity in human hepatoma line

Nitrites are ubiquitous environmental contaminants present in drinking water and foods. Nitrosamines can be formed endogenously from nitrate and nitrite and secondary amines or may be present in food, tobacco smoke, and drinking water. The major goal of this work was to evaluate the cytotoxic, reactive oxygen species (ROS)-producing and genotoxic effects of nitrite and nitrosamines and the possible protection by ascorbic acid in HepG2 cells. It was found that nitrite, N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), and N-nitrosomorpholine (NMOR) decreased cell viability, increased intracellular ROS production, and caused genotoxicity. Compared to untreated cells as determined by alkaline Comet assay, nitrite, NDMA, NDEA, and NMOR raised the tail intensity up to 1.18-, 3.79-, 4.24-, and 4.16-fold, respectively. Ascorbic acid (AA, 10 μM) increased cell viability and reduced ROS production significantly (p < 0.05). Additionally, AA treatment decreased the tail intensity caused by nitrite, NDMA, NDEA, and NMOR to 33.74%, 58.6%, 44.32%, and 43.97%, respectively. It can be concluded that ascorbic acid was able to reduce both tail intensity and tail moment in all of the nitrosamine treatments, particularly in NDMA. AA protected HepG2 cells against genotoxic effects caused by nitrosamines. This protection might be through different mechanisms, some of which are not still understood in depth. The future interest will be to understand which pathways are influenced by antioxidants, particularly by AA, and the outcomes of this prevention in other cell line types.

Neopterin, Catalase and Superoxide Dismutase in Females with Benign and Malignant Breast Tumors

Abstract The aim of the present study was to evaluate the relationship between the levels of neopterin among patients with benign and malignant breast disease and the relation with the stage of the malignant process. In this study, neopterin concentrations and enzyme activities of superoxide dismutase (SOD) and catalase (CAT) were determined in malign (n=30) and benign breast tumor patients (n=30) by high performance liquid chromatographic and spectrophotometric methods, respectively. Results were compared with a healthy control group (n=20). The correlations between neopterin, CAT and SOD were also evaluated in controls and patients. Urinary neopterin level of the control group was (mean value ± S.D.) 128.6 ± 64.6 μmol/mol creatinine. Neopterin concentrations in patients with breast malignancy were 153.6 ± 71.2 μmol/mol creatinine and 107.8 ± 32.1 μmol/mol creatinine in benign disorders patients. The mean neopterin level in the benign group was found to be statistically different from the malign tumor group (p = 0.039). SOD and CAT activities in controls were found as 3.57 ± 0.84 U/mg protein and 2.19 ± 0.20 U/mg protein, respectively. In patients with malignancy, the SOD activity was 3.84 ± 0.73 U/mg protein while CAT activity was 1.03 ± 0.13 U/mg protein. Patients with benign breast disorders, SOD activity was 4.09 ± 1.00 U/mg protein and CAT activity was 1.02 ± 0.18 U/mg protein. Whereas SOD activity did not differ between the groups of patients and controls, the mean catalase level in the control group was higher than in the benign and malign tumor groups (both p <0.001). Urinary neopterin concentration seems to be an important and useful biomarker in diagnosis of breast tumors in clinical practice.

Effects of the metals on dihydropteridine reductase activity

Metals are the oldest toxins known to human. Particularly, occupational and environmental exposure to aluminium, lead, mercury, cadmium, and manganese cause serious health problems by interaction with biological systems. Cellular targets of these metals are mostly specific biochemical processes (enzymes) and/or membranes of cells and organelles. To prevent and/or reduce the untoward or irreversible toxic effects of the metals by using biomarkers are as important as to know and to understand of their toxicity mechanisms. Dihydropteridine reductase (DHPR), which possessed essential thiol groups at the activity site, plays a crucial role in the maintenance of tetrahydrobiopterin (BH4). BH4 is the cofactor in the synthesis and regulation of neurotransmitters. A limited number of the evidences have shown that DHPR may be a target for the metals. Therefore, the present study was designed to assess possible in vitro effects of the commonly exposed metals on the enzyme activity. It was found that aluminium, cadmium, mercury, di-phenyl mercury, lead, diethyl lead, in chloride forms, and manganese, in sulphate form, led to statistically significant decreases in DHPR activity, in a concentration-dependent manner, in vitro.

Chronopharmacokinetics of drugs in toxicological aspects: A short review for pharmacy practitioners

A rough 24-hour cycle driven endogenously in biochemical, physiological or behavioral processes is called circadian rhythm. Chronobiology is the study of biological temporal rhythms. For decades, we know that the biological rhythm and the drug metabolism are also affected from daylight and chronopharmacology became recognized by scientists in the early 1970s. Its lateral branch chronocopharmacokinetics is the study of rhythmic, predictable-in-time differences in the pharmacokinetics of drugs. Chronopharmacokinetic studies are performed at every step of the biotransformation i.e., absorption, distribution, metabolism and excretion. Feeding schedules, sex and phenotype must be taken into consideration while applying pharmacotherapy to increase the efficiency and to decrease side effects. The impact of drugs on circadian rhythm should be not neglected. On the other hand, new special drug delivery systems can be used to synchronize drug concentrations according to circadian rhythms. “Chronopharmaceuticals” can identify the proper dosing time and this amelioration will lead to improved progress and diffusion of pharmacotherapy. Chronopharmaceuticals coupled with nanotechnology could be the future of drug delivery systems, and lead to safer and more efficient disease therapy in the future. In this review, we will discuss the pharmacokinetic effects of circadian rhythm and its toxicological outcomes. Besides, we will try to give some practical points for clinical pharmacist/pharmacy practitioners, concerning chronopharmacokinetics.

Chronopharmacodynamics of drugs in toxicological aspects: A short review for clinical pharmacists and pharmacy practitioners

For many decades, researchers are aware of the importance of circadian rhythm in physiological/biochemical properties and drug metabolism. Chronopharmacology is the study of how the effects of drugs vary with biological timing and endogenous periodicities. It has been attaching substantial attention in the last years. Chronopharmacodynamics mainly deals with the biochemical and physiological effects of drugs on the body, the mechanisms of drug action, the relationship between drug concentration and effect in relation to circadian clock. In this review, we will focus on mammalian circadian pharmacodynamics and discuss new chronotherapy approaches. Moreover, we will try to highlight the chronopharmacodynamics of cardiovascular drugs, anti-cancer drugs, analgesics and non-steroidal anti-inflammatory drugs (NSAIDs) and give some practical concerns for clinical pharmacists and pharmacy practitioners, concerning this issue.