ARIA pharmacy 2018 "Allergic rhinitis care pathways for community pharmacy": AIRWAYS ICPs initiative (European Innovation Partnership on Active and Healthy Ageing, DG CONNECT and DG Santé) POLLAR (Impact of Air POLLution on Asthma and Rhinitis) GARD Demonstration project.

Pharmacists are trusted health care professionals. Many patients use over-the-counter (OTC) medications and are seen by pharmacists who are the initial point of contact for allergic rhinitis management in most countries. The role of pharmacists in integrated care pathways (ICPs) for allergic diseases is important. This paper builds on existing studies and provides tools intended to help pharmacists provide optimal advice/interventions/strategies to patients with rhinitis. The Allergic Rhinitis and its Impact on Asthma (ARIA)-pharmacy ICP includes a diagnostic questionnaire specifically focusing attention on key symptoms and markers of the disease, a systematic Diagnosis Guide (including differential diagnoses), and a simple flowchart with proposed treatment for rhinitis and asthma multimorbidity. Key prompts for referral within the ICP are included. The use of technology is critical to enhance the management of allergic rhinitis. However, the ARIA-pharmacy ICP should be adapted to local healthcare environments/situations as regional (national) differences exist in pharmacy care.

Detection of ALDH3B2 in Human Placenta.

Aldehyde dehydrogenase 3B2 (ALDH3B2) gene contains a premature termination codon, which can be skipped or suppressed resulting in full-length protein expression. Alternatively, the longest putative open reading frame starting with the second in-frame start codon would encode short isoform. No unequivocal evidence of ALDH3B2 expression in healthy human tissues is available. The aim of this study was to confirm its expression in human placenta characterized by the highest ALDH3B2 mRNA abundance. ALDH3B2 DNA and mRNA were sequenced. The expression was investigated using western blot. The identity of the protein was confirmed using mass spectrometry (MS). The predicted tertiary and quaternary structures, subcellular localization, and phosphorylation sites were assessed using bioinformatic analyses. All DNA and mRNA isolates contained the premature stop codon. In western blot analyses, bands corresponding to the mass of full-length protein were detected. MS analysis led to the identification of two unique peptides, one of which is encoded by the nucleotide sequence located upstream the second start codon. Bioinformatic analyses suggest cytoplasmic localization and several phosphorylation sites. Despite premature stop codon in DNA and mRNA sequences, full-length ALDH3B2 was found. It can be formed as a result of premature stop codon readthrough, complex phenomenon enabling stop codon circumvention.

The utility of saliva testing in the estimation of uremic toxin levels in serum.

Background p-Cresol sulfate (pCS) and indoxyl sulfate (IS) are uremic toxins, high concentrations of which are related to renal failure progression. Saliva could become the first-line diagnostic sample of choice, especially for monitoring purposes. Recently, a method for determination of pCS and IS in saliva was developed. Since no data exist on correlations between the levels of toxins in saliva and serum, the applicability of saliva as a diagnostic material is yet to be established. Here, we present a study on the assessment of the utility of saliva testing in the estimation of uremic toxin levels in serum. Methods The study material included serum and unstimulated, fasting saliva obtained from healthy volunteers (n=26) and patients at all stages of chronic kidney diseases (CKD, n=93). The concentration of pCS and IS in saliva and serum (total and unbound fractions) was determined. The daytime variation of the toxins was studied. Results A correlation was found between pCS and IS in saliva and biological active fractions in serum (0.74; 0.81). The variation of the serum/saliva ratio during the day was negligible, with a median of 10% for pCS and 6% for IS, making saliva a reliable material for the estimation of the uremic toxins in circulation at any time of the day. Significant correlations were observed between salivary toxin levels and estimated glomerular filtration rate (pCS: -0.61; IS: -0.70) as well as significant differences in toxin levels between the stages of CKD. Conclusions Saliva could be a valuable diagnostic material for the estimation of toxin levels in circulation.

Application of 2-Aminothiazoline-4-carboxylic Acid as a Forensic Marker of Cyanide Exposure.

Cyanides are infamous for their highly poisonous properties. Accidental cyanide poisoning occurs frequently, but occasionally, intentional poisonings also occur. Inhalation of fumes generated by fire may also cause cyanide poisoning. There are many limitations in direct analysis of cyanide. 2-Aminothiazoline-4-carboxylic acid (ATCA), a cyanide metabolite, seems to be the only surrogate that is being used in the detection of cyanide because of its stability and its cyanide-dependent quality in a biological matrix. Unfortunately, toxicokinetic studies on diverse animal models suggest significant interspecies differences; therefore, the attempt to extrapolate animal models to human models may be unsuccessful. The aim of the present study was to evaluate the use of ATCA as a forensic marker of cyanide exposure. For this purpose, post-mortem materials (blood and organs) from fire victims (n = 32) and cyanide-poisoned persons (n = 3) were collected. The distribution of ATCA in organs and its thermal stability were evaluated. The variability of cyanides in a putrid sample and in the context of their long-term and higher temperature stability was established. The presence of ATCA was detected by using an LC-MS/MS method and that of cyanide was detected spectrofluorimetrically. This is the first report on the endogenous ATCA concentrations and the determination of ATCA distribution in tissues of fire victims and cyanide-poisoned persons. It was found that blood and heart had the highest ATCA concentrations. ATCA was observed to be thermally stable even at 90 °C. Even though the cyanide concentration was not elevated in putrid samples, it was unstable during long-term storage and at higher temperature, as expected. The relationship between ATCA and cyanides was also observed. Higher ATCA concentrations were related to increased levels of cyanide in blood and organs (less prominent). ATCA seems to be a reliable forensic marker of exposure to lethal doses of cyanide.

Antazoline-insights into drug-induced electrocardiographic and hemodynamic effects: Results of the ELEPHANT II substudy.

BACKGROUND: Antazoline is an old antihistaminic and new antiarrhythmic agent with unknown mechanisms of action which recently has been shown to effectively terminate atrial fibrillation. The aim of study was to examine the effects of antazoline on hemodynamic and ECG parameters. METHODS: Antazoline was given intravenously in three 100 mg boluses to 10 healthy volunteers (four males, mean age 40 + 11 years). Hemodynamic and ECG parameters were measured using impedance cardiography [systolic (sBP), diastolic (dBP), mean (mBP) blood pressure, stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR) and heart rate (HR), P wave, PR interval, QRS complex, QT and corrected QT (QTcF) interval]. Plasma concentration of antazoline was also measured. RESULTS: Antazoline caused significant prolongation of P wave, QRS as well as QT and QTcF (101 ± 10 vs 110 ± 16 ms, p < .05, and 101 ± 12 vs 107 ± 12 ms, p < .05, 399 ± 27 vs 444 ± 23 ms, p < .05, and 403 ± 21 vs 448 ± 27 ms, p < .05, respectively). Also, a significant decrease in SV was noted (94.9 ± 21.8 vs 82.4 ± 19.6 ml, p < .05). A significant correlation between changes in plasma drug concentration and changes in CO, HR, and dBP was found. CONCLUSIONS: Antazoline impairs slightly hemodynamics, significantly reducing SV. Significant prolongation of P wave and QRS duration corresponds to drug-induced prolongation of conduction, whereas QT prolongation represents drug-induced prolongation of repolarization.

Protective Effects of Selol Against Sodium Nitroprusside-Induced Cell Death and Oxidative Stress in PC12 Cells.

Selol is an organic selenitetriglyceride formulation containing selenium at +4 oxidation level that can be effectively incorporated into catalytic sites of of Se-dependent antioxidants. In the present study, the potential antioxidative and cytoprotective effects of Selol against sodium nitroprusside (SNP)-evoked oxidative/nitrosative stress were investigated in PC12 cells and the underlying mechanisms analyzed. Spectrophoto- and spectrofluorimetic methods as well as fluorescence microscopy were used in this study; mRNA expression was quantified by real-time PCR. Selol dose-dependently improved the survival and decreased the percentage of apoptosis in PC12 cells exposed to SNP. To determine the mechanism of this protective action, the effect of Selol on free radical generation and on antioxidative potential was evaluated. Selol offered significant protection against the elevation of reactive oxidative species (ROS) evoked by SNP. Moreover, this compound restored glutathione homeostasis by ameliorating the SNP-evoked disturbance of GSH/GSSG ratio. The protective effect exerted by Selol was associated with the prevention of SNP-mediated down-regulation of antioxidative enzymes: glutathione peroxidase (Se-GPx), glutathione reductase (GR), and thioredoxin reductase (TrxR). Finally, GPx inhibition significantly abolished the cytoprotective effect of Selol. In conclusion, these results suggest that Selol effectively protected PC12 cells against SNP-induced oxidative damage and death by adjusting free radical levels and antioxidant system, and suppressing apoptosis. Selol could be successfully used in the treatments of diseases that involve oxidative stress and resulting apoptosis.

THE MEASUREMENT OF ANTIOXIDANT CAPACITY AND POLYPHENOL CONTENT IN SELECTED FOOD SUPPLEMENTS.

Oxidative stress (OS), defined as a disturbance in the balance between the production of reactive oxygen species (ROS) and antioxidant defenses, can result in the development of many serious diseases like diabetes or cancer. Moreover, the role of oxidative stress in the acceleration of the aging process is also confirmed. ROS are constantly produced in the natural biochemical processes, mainly during cellular respiration. Their enhanced production may be the result of e.g., an inappropriate diet high in saturated fats, low in fiber, fruits and vegetables, insufficient physical activity or smoking. To prevent oxidative stress, besides changes in life style, the additional supplementation of antioxidants is proposed. On the Polish market, the number of food supplements with declared antioxidant activity is still increasing. However, their antioxidant properties are rarely confirmed experimentally. The aim of our study was to determine the antioxidant potential of selected dietary supplements available on the market and recommended in chronic fatigue syndrome. The antioxidant potential was measured using four methods: FRAP, ORAC, HORAC, EPR/DPPH. Moreover, the content of polyphenols in the dietary supplements was also determined.

The analysis of plant-based raw materials of unknown origin.

Chosen aspects of the safety of use of several herbs received from National Medicines Institute, which came from smuggling, have been examined. The analysis has been conducted in three different aspects: (1) Possibilities of contamination of plant-based raw materials by metals of heavy elements (As, Cd, Cu, Cr, Pb). (2) Conscious smuggling of intoxicating preparation or narcotics in plant-based raw materials. (3) Radioactive contamination originating mostly from 137Cs isotope. To solve the problem, analytical methods of GFAAS and ICP-MS, X-ray diffraction and high-distributive spectrometry of gamma-radiation have been applied. Determined concentration of arsenic in all analyzed samples and the concentration of lead in one sample exceeded allowable concentration recommended by WHO. In analyzed materials, no presence of narcotics or radioactive contamination of 137Cs isotope has been detected.

Contribution of ALDH1A1 isozyme to detoxification of aldehydes present in food products.

Even though food awareness is so developed and more and more people pay attention to what their diet is composed of, it is not possible to exclude all potentially dangerous substances present in our diet. One group of such compounds may be aldehydes as several studies indicate that they can be mutagenic, carcinogenic, genotoxic and cytotoxic. These relatively reactive organic molecules are natural constituents of food. They are also extensively used by food industry as additives giving aroma and taste. Fortunately many enzyme systems were developed to protect us against these toxic compounds, one of which is aldehyde dehydrogenase enzyme superfamily. As mouth is the first part of digestive system it seems crucial for detoxifying toxic substances introduced with our diet. The only ALDH isozyme present in saliva is ALDH3A1, which has very high affinity towards aromatic aldehydes commonly found in food. However, because of hyposalivation, which is not uncommon nowadays, the effectiveness of this barrier can be drastically diminished. As another member of this enzyme family, isozyme ALDH1A1 is also present in digestive system its possible contribution to detoxification of "food" aldehydes was addressed. Kinetic parameters (Km, Vmax) of recombinant ALDH1A1 towards several aliphatic and aromatic aldehydes occurring in food products (vanillin, citral, furfural, cinnamaldehyde, anisaldehyde, benzaldehyde and trans-hexenal) were determined by measuring the increase of NADH fluorescence after adding various concentrations of aldehyde substrates. Rates were used to construct the Lineweaver-Burk plot from which Km and Vmax (measured relative to that of benzaldehyde which was assigned the value of 100) values were calculated. The following results were obtained: 0.04 +/- 0.06 microM and 277 +/- 81 for anisaldehyde, 0.86 +/- 0.03 mciroM and 50 +/- 3 for vanillin, 0.18 +/- 0.05 mciroM and 93 +/- 9 for trans-2-hexenal, 0.17 +/- 0.03 microM and 201 +/- 32 for cinnamaldehyde, 5.8 +/- 0.3 mciroM and 281 +/- 59 for furfural, 0.65 +/- 0.05 microM and 139 +/- 9 for citral, 0.4 +/- 0.2 microM and 100 for benzaldehyde. It turned out that this ubiquitous member of ALDHs superfamily, has very good affinity for examined aldehydes. The resulting Michaelis - Menten constant values are even lower than the corresponding values for ALDH3A1 enyzme. Thus supporting role of ALDH1A1 in the protection of organisms against these dangerous compounds from food can be suggested.

Exposure to ionizing radiation of workers in Poland.

Results of individual monitoring of occupied workers based on the doses estimations carried out by Central Laboratory for Radiological Protection (CLOR) in Warsaw has been presented. In 2011, about 5000 persons from 330 institutions were monitored. Monitoring service in CLOR is based on two doses assessment methods, Kodak films and MCP-N thermo luminescent detectors. Presented results show that 97% of registered doses were less than 1 mSv and only about 0.1% of assigned doses were higher than 20 mSv. The monitored workers were divided in four groups: medical, scientific, industrial and others. Six cases of excess of the 20 mSv annual dose limit were registered in medical, three in scientific and three in industrial group. The average annual dose in each particular group was calculated: 0.51 mSv in medical, 0.62 mSv in scientific, 0.48 mSv in industrial and 0.44 mSv in others.

Determination of selected elements in different pharmaceutical forms of some Polish herbal medicinal products.

In the present work, the following microelements and heavy metals were determined in the Willow bark (Cortex Salicis), in the St. John's wort (Herba Hyperici), in the infusions from these raw materials and in the tablets containing these herbs: Cr, Cu, Fe, Ni, Zn and Ba, Cd, Pb. The concentration of the metals were determined by means of the GFAAS and ICP-MS methods. Considering the examined two herbs as a source of toxic metals, the occurrence of high levels (exceeding the European Pharmacopoeia limits) of Cd should be emphasized. The level of cadmium was low in the infusions because of a low extraction efficiency of this metal, so that the infusions can be found as a rather safe form of herbal medicine. In the tablets, the Cd contents were similar to the levels found in the raw materials. Because the total heavy metal content can be accessible, it may cause a potential health risk for human.

Exploring associations of anthropometric parameters and serum triglycerides with serum thyroid hormones in young women.

Establishing links between serum thyroid hormone panel and triglyceride (TG) concentrations with non-invasively obtained measurements of anthropometric parameters of young women may provide preliminary knowledge about the homeostasis of metabolic processes and body composition and about the strategic role of the tested parameters as early screening tests for assessing the health status of apparently healthy women in the period preceding pregnancy. The study was conducted in 381 healthy female students (aged 18-26 years, mean ± SD = 22.1 ± 1.3). Anthropometric indices (BMI, waist-to-hip ratio, FAT%) were calculated and serum concentrations of thyroid hormones (TSH, fT3, fT4) were determined using electrochemiluminescence immunoassays and serum triglycerides (TG) with a commercially available test. No association was established between serum TSH and anthropometric indices in healthy young women. Increased serum concentrations of fT4, fT3 and TG were found in overweight subjects, i.e. BMI > 24.9 kg/m2 (p < 0.05). A significant negative association between fT3 and TG was found in underweight subjects (r = - 0.258, p = 0.049) and a significantly positive association in normal-weight subjects (r = 0.139, p = 0.019). In healthy young women differences in BMI are not related to thyroid function. The opposite directions between the associations fT3 vs TG in underweight compared to normal-weight young prepregnant females may suggest dependencies of fT3 and TG in the regulation of specific BMI-dependent metabolic processes.

Comparison of antioxidant enzymes activity and the concentration of uric acid in the saliva of patients with oral cavity cancer, odontogenic cysts and healthy subjects.

Chronic inflammation is related to oxidative stress and is still believed to be the cause of carcinogenesis. Patients with oral cavity cancer (OCC) exhibited lower total antioxidant capacity, uric acid (UA) concentration, salivary peroxidise (SPO) and superoxide dismutase (SOD) activity in their saliva than did healthy subjects. This could be a risk factor for tumour induction. Odontogenic cysts also arise in response to locally acting proinflammatory factors, for example, a gangrenous tooth. Furthermore, cyst development is accompanied by chronic inflammation. There are some reports in the literature concerning primary tumours such as squamous cell carcinomas arising from odontogenic cysts. The reason for this transformation is still unknown. The aim of this study was to compare the status of the antioxidant defence system in the saliva of the group with odontogenic cysts and OCC with that of the healthy control. Saliva samples were collected in the morning. SOD, SPO activity and UA concentration were determined using standard methods. Patients with odontogenic cysts and OCC exhibited lower activity of major antioxidants in their saliva (SPO, UA) than did healthy people. SOD activity and age are the main factors that distinguish these diseases. Discriminant function analysis showed that once data such as antioxidant status of saliva, age and smoking status are known 80% cases can be correctly classified as healthy, 80% as having odontogenic cysts and 40% as cancerous. To conclude, the decrease in concentrations of major antioxidants in the saliva of patients with cysts may increase the risk of neoplastic transformation especially in advanced age.

Salivary aldehyde dehydrogenase activity--influence of drugs intake, preliminary research.

The salivary aldehyde dehydrogenase (ALDH3A1) oxidizes mainly aromatic and long chain aliphatic aldehydes. This enzyme protects organisms from aldehydes originating from food and air pollution, and can also be an important factor in chemical carcinogenesis prevention. In the majority of saliva samples the ALDH3A1 is more than in 60% inactive due to sulfhydryl groups oxidation in the active site. Our previous studies showed that the ALDH3A1 activity (the total activity and the inactivation degree) is strongly variable during a day and within the healthy population. The aim of the present study was to describe the influence of drugs intake on ALDH3A1 activity. Hierarchical clustering grouped two dimensional data (the total ALDH activity, the inactivation degree) derived from a group of 124 subjects into four clusters. Clusters were analyzed by a correspondence analysis. The total ALDH3A1 activity and an inactivation degree vary in healthy subjects depending on many factors including cigarette smoking, alcohol and coffee consumption and age. This work demonstrates that treated hypertension and acute pain/infection as well as hormonal contraceptive drugs intake also significantly affect the salivary ALDH activity. The result is significant for food safety and nutrition research.

Cloud Point Extraction in the Determination of Drugs in Biological Matrices.

Cloud point extraction (CPE) is a simple, safe and environment-friendly technique used in the preparation of various samples. It was primarily developed for the assessment of environmental samples, especially analyzed for metals. Recently, this technique has been used in the extraction and determination of various chemical compounds (e.g., drugs, pesticides and vitamins), in various matrices (e.g., human plasma, human serum, milk and urine). In this review, we show that CPE is a reliable method of extraction and can be used in analytical laboratories in combination with other techniques that can be used in the determination of drugs and other chemicals in the human biological matrix. According to the literature, a combination of different methods provides good recovery and can be used in the simultaneous determination of many drugs in a single analysis. CPE can be optimized by changing its conditions (e.g., type of surfactant used, incubation temperature, pH and the addition of salts). In this review, we present the optimized CPE methods used in the determination of various pharmaceuticals and describe how the conditions affect the performance of extraction. This data might support future designing of the new CPE applications that are simple and more accurate. We compared CPE with other extraction methods and also showed the advantages and disadvantages of various extraction techniques along with a discussion on their environmental impact. According to the publications reviewed, it is obvious that CPE is an easy, safe, rapid and inexpensive method of extraction.

Oxidative Stress Markers Differ in Two Placental Dysfunction Pathologies: Pregnancy-Induced Hypertension and Intrauterine Growth Restriction.

AIM: Pregnancy-induced hypertension (PIH) and intrauterine growth restriction (IUGR) are both multisystemic disorders of pregnancy that cause perinatal morbidity and mortality. Recently, researchers focused on the role of oxidative stress (OS) as a pathophysiological mechanism in the development of these pathologies. The aim of this study was to compare OS in placental-related pathologies (PIH and IUGR) and uncomplicated pregnancies. We also investigated which salivary OS markers reflect systemic oxidative status and which only reflect the state of the oral cavity. Material and Methods. A total of 104 pregnant women (n = 104; 27 with PIH, 30 with IUGR, and 47 controls) were evaluated. Malondialdehyde (MDA), total antioxidant capacity (ORAC), aldehyde dehydrogenase (ALDH), and activity of glutathione peroxidase (GPx) and glutathione transferase (GST) in plasma/whole blood and/or saliva were analysed. Dietary nutrient intake was calculated using a Semiquantitative Food Frequency Questionnaire (SFFQ). Oral health was assessed to eliminate patients with bleeding, severe periodontitis, and other dental pathologies. RESULTS: In the IUGR group, increased concentration of ORAC was observed both in saliva and plasma. Also, lower plasma levels of MDA in IUGR compared to the control group was detected. No sign of oxidative stress was confirmed in the PIH group. The examined groups did not differ regarding diet and markers of inflammation. ORAC in saliva was correlated with its level in plasma. No such correlations for MDA were observed. In the IUGR group, there were no differences in OS markers in plasma, but there was a lower ALDH level in the blood compared to the control group. It confirms OS occurrence in IUGR. In IUGR, a higher activity of salivary ALDH was probably due to worse oral health. CONCLUSION: Oxidative stress differs between IUGR and PIH groups: the presence of oxidative stress was confirmed only in the IUGR group. Salivary ORAC can be used to estimate ORAC in plasma. The activity of salivary ALDH reflects the state of the oral cavity.

Acute exposure of zebrafish (Danio rerio) larvae to environmental concentrations of selected antidepressants: Bioaccumulation, physiological and histological changes.

Antidepressants have been detected in surface waters worldwide at ng-µg/L concentration. These compounds can exert adverse effects on fish even at low levels. But, all previous analyses have concentrated on adult fish. The aim of the study was to assess the effect of environmental concentrations of sertraline, paroxetine, fluoxetine and mianserin, and their mixtures on such unusual endpoints as physiological and histological changes of zebrafish (Danio rerio) larvae. We also determined the bioconcentration of the pharmaceuticals. Fish Embryo Toxicity test was used to analyze the influence on developmental progression. Histological sections were stained with hematoxylin and eosin. Proliferating cells in liver were determined immunohistochemically by detection of Proliferating Cell Nuclear Antigens. The bioconcentration factor was measured by liquid chromatography coupled to mass spectrometry. Pharmaceuticals were used at low, medium and high concentrations in mixtures and at medium concentration as single compound. Exposure to the analyzed pharmaceuticals increased the rate of abnormal embryo and larvae development, accelerated the hatching time and affected the total hatching rate. Three-times lower proliferation of hepatocytes was observed in larvae exposed to paroxetine, mianserin, sertraline and the mixture of the pharmaceuticals at the highest concentrations. The highest bioaccumulation factor (BCF) was obtained for sertraline. The BCF of the analyzed compounds was higher if the organisms were exposed to the mixtures than to single pharmaceuticals. To conclude, the exposure of zebrafish larvae to selected antidepressants and their mixtures may cause disturbances in the organogenesis of fish even at environmental concentrations.

Salivary aldehyde dehydrogenase: activity towards aromatic aldehydes and comparison with recombinant ALDH3A1.

A series of aromatic aldehydes was examined as substrates for salivary aldehyde dehydrogenase (sALDH) and the recombinant ALDH3A1. Para-substituted benzaldehydes, cinnamic aldehyde and 2-naphthaldehydes were found to be excellent substrates, and kinetic parameters for both salivary and recombinant ALDH were nearly identical. It was demonstrated that for the fluorogenic naphthaldehydes the only produced reaction product after incubation in saliva is the carboxylate.

The oxidation status of ALDH3A1 in human saliva and its correlation with antioxidant capacity measured by ORAC method.

Oxidation status of the salivary aldehyde dehydrogenase (ALDH) was measured in healthy human population using two-assay fluorimetric method and compared with antioxidant capacity (ORAC) in non-smoking and heavy smokers group. Influence of high or low antioxidant diet was also examined. Except for the group of smokers, the salivary ALDH oxidation degree in human saliva was not correlated with antioxidant capacity. Simultaneously direct administration of the antioxidant-containing drug, Fluimucil, resulted in short-term, but statistically significant increase of the reduced (active) form of the enzyme, presumably due to a radical-scavenging activity of the drug.