Number Of Active Substances Research Articles

Beneficial clinical effects of honey from bees fed with specific plant extracts

Abstract Background Our team has demonstrated in a number of pre-clinical studies that special bees fed with syrups containing natural plant extracts contain a number of active substances that have beneficial effects on the human body. We have previously reported that bees fed with green walnut have beneficial effects on sugar metabolism, lowering serum glucose levels and reducing insulin resistance. Methods We conducted a prospective double-blind functional food study with 45 healthy volunteers using a strict inclusion and exclusion criteria with ethical approval. Participants ate 30 gramms of honey layered under 150 ml of yoghurt twice a day for 3 weeks. Fifteen participants consumed honey from bees fed with green walnut extract, while 15 participants consumed honey from bees fed with sea buckthorn extract, and 15 participants in the control group consumed acacia honey. Sleep quality was assessed with the SQS questionnaire, and quality of life with the SF-36, EORTC Q-C30 and EQ-5D tests on days 0 and 22 of the study. Results Consumption of both specific honey resulted improvements in the life quality parameters and in the sleep quality. ‘Buckthorn honey’ showed significant differences after the 3rd week: physical function improved (25.3±0.5 vs 27.4±2.8; p = 0.04), anxiety-depression decreased (1.4±3.6 vs 1±0.3; p = 0.03), complex physical status (84.1±9.7 vs 88.7±6.9; p = 0. 04), while ‘green walnut honey’ improved EQ-5D complex quality of life (84.1±9.7 vs 88.9±6.9; p = 0.01), overall quality of life functioning (90.6±14.9 vs 99.2±4.2; p = 0.03), EORTC Q-C30 total score (467.1±30.6 vs 487.4±21.4; p = 0.03).No such positive effects were confirmed in the control group. Conclusions Honey from bees fed with sea buckthorn extract has many beneficial physiological effects on the human body, improving physical well-being and reducing anxiety and depression. Honey from bees fed with green walnut extract improves the complex quality of life. Key messages • Improving the quality of life with nutrition is an increasingly important research field, playing a key role in our life. • Our research has shown that honey from bees fed with green walnut and sea buckthorn extract improves several parameters in the quality of life.

Fermentation of waste water from agar processing with Bacillus subtilis by metabolomic analysis.

Fungal infection has become a major threat to crop loss and affects food safety. The waste water from agar processing industries extraction has a number of active substances, which could be further transformed by microorganisms to synthesize antifungal active substances. In this study, Bacillus subtilis was used to ferment the waste water from agar processing industries extraction to analyze the antifungal activity of the fermentation broth on Alternaria alternata and Alternaria spp. Results showed that 25% of the fermentation broth was the most effective in inhibited A. alternata and Alternaria spp., with fungal inhibition rates of 99.9% and 96.1%, respectively, and a minimum inhibitory concentration (MIC) was 0.156μg/mL. Metabolomic analysis showed that flavonoid polyphenols such as coniferyl aldehyde, glycycoumarin, glycitin, and procyanidin A1 may enhance the inhibitory activity against the two pathogenic fungal strains. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that polyphenols involved in the biosynthesis pathways of isoflavonoid and phenylpropanoid were upregulated after fermentation. The laser confocal microscopy analyses and cell conductivity showed that the cytoplasm of fungi treated with fermentation broth was destroyed. This study provides a research basis for the development of new natural antifungal agents and rational use of seaweed agar waste. KEY POINTS: • Bacillus subtilis fermented waste water has antifungal activity • Bacillus subtilis could transform active substances in waste water • Waste water is a potential raw material for producing antifungal agents.

Mitigating the Risk of Drug Interactions in Cancer Patients Taking Oral Anticancer Agents: The Role of a Multidisciplinary Team-Based Medication Reconciliation.

Polypharmacy in cancer patients is a recognized issue and should be an integral part of comprehensive patient assessment and management. Despite this, a systematic review of concomitant drugs or a search for potential drug-drug interactions (DDIs) is not always performed. Here, we present the results of a medication reconciliation model performed by a multidisciplinary team to identify clinically meaningful potential DDIs (defined by the presence of DDIof major severity or contraindication) in cancer patients undergoing oral antineoplastic drugs. From June to December 2022, we performed a non-interventional, prospective, cross-sectional, single-center study of adult cancer patients, initiating or undergoing treatment with oral antineoplastic drugs, referred by their oncologists for therapeutic review regarding potential DDIs. DDIs were assessed by a multidisciplinary team of hospital pharmacists and medical oncologists, through research in three different drug databases as well as in the summary of product characteristics. A report detailing all potential DDIs was created for each request and provided to the patient's medical oncologist for further examination. Overall, 142 patients' medications were reviewed. Regardless of the severity or clinical importance, 70.4% of patients had at least one potential DDI. We found 184 combinations of oral anticancer and regular therapy agents with potential DDIs, 55 of whom were considered of major severity by at least one DDI database. As expected, the number of potential DDIs increased with the number of active substances in regular therapy (p <0.001), but we did not find an increased relation between age and the total number of potential DDIs (p =0.109). Thirty-nine (27.5%) patients had at least one clinically meaningful DDI identified. After adjustment through multivariable logistic regression, only the female sex (odds ratio (OR) 3.01,p= 0.029), the number of active comorbidities (OR 0.60,p= 0.029), and the presence of proton pump inhibitors in chronic medication (OR 2.99,p= 0.033) remained as predictors of potential meaningful DDI. Although drug interactions are a concern in oncology, a systematic DDI review is rarely conducted in medical oncology consultations. The availability of a medication reconciliation service, carried out by a multidisciplinary team with dedicated time for this task, is an added value for safety enhancement in cancer patients.

Pesticide Residues in Bananas from the Canary Islands.

There are a large number of pests which are detrimental to plant production, specifically to banana cultivation, and the use of pesticides is the main method of control of these pests. Therefore, the number of active substances in pesticides has been steadily increasing since before the Second World War. There is growing consumer concern about the health effects of pesticide residues and there is certainly evidence of a link between pesticide exposure and the prevalence of chronic diseases. Therefore, it is of particular interest to study the presence of pesticide residues in bananas and their toxicological, agricultural and legal implications. In this study, the content of pesticide residues in bananas produced in the Canary Islands during a ten-year period from 2008 to 2017 was determined. A total of 733 samples of bananas were analysed during the study period, in which 191 different active substances were investigated, involving 103,641 assessments. The samples analysed were selected in such a way that they are representative of the banana sector in the Canary Islands as a whole, taking into account geographical and climatic factors, cultivation methods and the processing of bananas in packaging, which are the differentiating factors in the use of pesticides. The reference parameter for the residue investigation is the MRL (maximum residue limit).

Yurt Dışı İlaçlar Hakkında Hastaya Yeterli ve Güvenilir Bilgi Sağlanmamasının İlaç Güvenliği ve Etik Sorunlar Açısından Analizi: Nitel Araştırma

Objective: The Imported Medicine List was published for the first time on October 11, 2013 by the Ministry of Health of the Republic of Türkiye. The purpose of importing drugs from abroad is to supply the human medicinal products that are not licensed in our country and/or that are not available in the market for various reasons despite being licensed, on prescription for use in the diagnosis and treatment of diseases in emergencies. The aim of this qualitative research is to examine the information presented about these medicines on the imported medicine list and to evaluate the possible ethical problems that may be caused by insufficient information presentation. Material and Methods: The medicines on the 25/02/2022 Turkish Medicines and Medical Devices Agency imported medicine list were included in the analysis. First, between the dates 07-27 February 2022, it was determined whether these medicines had short product information and instructions for use on the Turkish Medicines and Medical Devices Agency website by searching for active substances. Then, all medicines were searched in the RxMediaPharma database by the active substance name, and those not found by this method were searched by the ATC code. Finally, the ethical implications of the issue were discussed and suggestions were presented. Results: The change in the number of active substances in the imported medicine list by years and the presence of generic and medicine-specific information in different Informed Consent Forms have been determined. The ambiguity of the criteria for keeping the unlicensed essential drugs used to meet the priority health needs of the population in the foreign-dependent list has been determined. Conclusion: The risks to patients' right to autonomy have been determined as the result of the lack of sufficient, adequate, and accurate information in the Informed Consent Forms carries risks for patients' rights to autonomy.

Weed Management Challenges in Rice Cultivation in the Context of Pesticide Use Reduction: A Survey Approach

Weeds are the main phytosanitary problem in rice crop. Over-reliance on herbicides and lack of crop operations range in the rice system have produced intense selection for the evolution of resistant weed populations. This study focused on rice farmers’ perceptions and attitudes towards weeds and agricultural practices for weed management. The methodology of a questionnaire was used, carried out in person with rice producers in the main rice producing regions in Portugal, complemented by three focus groups. The outcomes reveal that Echinochloa spp. is the weed of greatest concern, followed by Oryza sativa var. sylvatica. New weeds are about to emerge, mainly Leptochloa fusca ssp. fascicularis. It will be critical for performance at the innovation ecosystem level to achieve evolution in social capital. Policies that promote innovation for the performance of more ecological and sustainable practices must be settled. The problem of herbicide resistance is increasing with the reduction in the number of active substances. There is great difficulty in adopting non-chemical weed control to meet the requirements of the European Ecological Pact. The implementation of these alternatives cannot be widespread, but must be studied on a case-by-case basis and requires technical monitoring adapted to the region and to the plot.

Evaluation of the Acaricidal Activity of Lithium Chloride against Tetranychus urticae (Acari: Tetranychidae)

Tetranychus urticae is a severe threat and a major source of yield loss in some agricultural and horticultural crops and it is also as a vector for several viruses. The number of active substances used against the pest is limited. Therefore, there is a continuous need for new active substances. Recently, lithium salts have been shown to be one of the most promising potential alternatives to control Varroa destructor; an apicultural mite pest. Based on this, we aimed to test whether the efficacy of lithium chloride extends to other agricultural mite pests, such as the two-spotted spider mite. In the present pilot study, we report for the first time that the efficacy of lithium chloride is extended to the two-spotted spider mite. Additionally, this is the first report on the acaricidal effectiveness of lithium on a plant mite pest. In the present study, we report three different concentrations that bear 100% mortality at concentrations of 5.52 M, 2.76 M, and 1.38 M. The symptoms caused were similar and followed the same sequence compared to those observed on animal parasites such as V. destructor and Dermanyssus gallinae.

Occurrence of pharmaceuticals in the wastewater of a Greek hospital: Combining consumption data collection and LC-QTOF-MS analysis

In this article we applied drug consumption approach and chemical analysis in parallel to investigate the concentrations of a large number of pharmaceuticals in different streams of a General Hospital. Drugs consumption data was collected during two periods (Period 1, 2) and the predicted environmental concentrations (PECs) were estimated for the wastewater of a building housing specific medical services (Point A) and for the entire hospital (Point B). Hospital wastewater samples (HWW) samples were also collected from these points and periods and the measured environmental concentrations (MEC) were determined using UHPLC-ESI-QTOF-MS/MS. According to consumption data, the highest number of drugs was consumed in the departments of Hematology, Intensive Care Unit, Cardiology, Internal Medicine, and Oncology, while the number of active substances used in the hospital was 413 (Period 1) and 362 (Period 2). For most substances, much higher PEC and MEC values were found at the HWW of Point A indicating that on-site treatment of this stream could be examined in the future. The application of wide-scope target analysis allowed the quantification of 122 compounds, while 21 additional substances were identified using suspect screening. The highest mean concentrations in Period 1 were found for acetaminophen (1100 μg/L) and rifaximin (723 μg/L), while in Period 2 for iopromide (458 μg/L) and acyclovir (408 μg/L). Among the detected compounds, 19 metabolites were determined. Atenolol acid, 1-hydroxy-midazolam and clopidogrel carboxylic acid were quantified at concentrations much higher than parent compounds indicating the importance of metabolites' monitoring in HWW. Calculation of PEC/MEC ratio for 36 pharmaceuticals showed sufficient correlation of these values for 19 % to 33 % of the substances depending on the examined period and sampling point. The parallel collection of drugs consumption data and chemical analysis give a thorough picture of the substances present in HWW and their main sources, facilitating decision-making for their better management.

Comparison of Extraction and Clean-up Methods Modified in Different Ways for the Determination of Pesticide Residues in Bees

As a result of the unconscious use of pesticides, honeybees are adversely affected, thus causing colony losses all over the world. In this research, different extraction and clean-up methods were compared on bee samples based on the QuEChERS method which is the most widely used pesticide analysis method in food. This research includes application studies for the multi residue method (MRM), which allows analysis of more than one pesticide. During the extraction phase, 7 different methods were compared, while the method with the most suitable repeatability and recovery values among these methods was taken to the clean-up phase. In the clean-up phase, 5 different clean-up methods were tried on the method which yielded the best values in extraction. In terms of average percentage recovery values, the 1stextraction method ranks first with 72 active substances between 70-120%, and the 3rd clean-up method with 92 active substances. Thus, while the number of active substances with suitable recovery values in the selected extraction method was 72, it increased to 92 with the continuation of the clean-up method, achieving a success rate of 92%. It is recommended to use this method in pesticide residue analyzes in bees with its outstanding features such as completing the analyzes in a short time, working easily with the infrastructure that can be found in all control laboratories, low analysis costs, ease of use, and reliability.

Herbal Medicines-Are They Effective and Safe during Pregnancy?

Since the teratogenicity of Thalidomide has been proven, herbal products are more commonly used in pregnancy to not only relieve morning sickness but also to fight infections. These products are frequently considered as natural and therefore harmless. However, herbs contain a number of active substances that, when used during pregnancy, can affect the development of the fetus. Often, pregnant women do not consult the usage of herbal medicines with a physician. The access to these products is easy and treatment of certain ailments with the use of herbs is common in many countries. The aim of the present literature review was to discuss available data regarding the efficacy and safety of cranberry, chamomile, Echinacea purpurea, garlic, ginger, Ginkgo biloba, and peppermint, which are used to counteract the most common ailments during pregnancy, i.e., infections and pregnancy-related ailments (e.g., nausea and vomiting, dizziness, and headache). Analysis of available data showed that ginger is one of the most extensively analyzed herbal remedies. The dose of ginger below 1000 mg per day may help to relief hypereremesis gravidarum, and such an amount of ginger did not increase frequency of adverse effects for either woman or developing fetus. Data regarding other herbs are most often heterogeneous and give conflicting results with no clear conclusions. However, all herbal products should be used with a special caution in pregnancy. Further high-quality human studies should be determined to confirm the safe doses of herbal products which could be used by pregnant or breast-feeding women.

Pesticide residues in bee pollen - validation of the gas chromatography-mass spectrometry multiresidual method and a survey of bee pollens from Slovenia

A new analytical method for determining environmental pesticide residues in pollen was introduced and validated. The extraction was conducted using acetonitrile, the clean-up using Supelclean Ultra 2400 solid phase extraction cartridges, which contain Grapsphere, anion exchanger, C18 and zirconia-based sorbent, and the determination was conducted using gas chromatography coupled with mass spectrometry. The method was applied in practice. A total of 49 active substances (pesticides) were sought in 30 bee pollen samples gathered from Slovenian beekeepers from all 12 statistical regions of Slovenia. The fungicide azoxystrobin was the only active substance found and was found only in one sample with a concentration of &lt; 0.05 mg kg-1. The active substances sought were not detected in 96.7 % of the samples analysed. The risk assessment revealed that the analysed pollen samples do not represent an unacceptable risk for consumers. The results were compared with those from the literature and the outcome was that bee pollen from Slovenia contained a lower number of active substances at mainly lower contents as compared pollen from some other European countries.

The French reporting system for drug shortages: description and trends from 2012 to 2018: an observational retrospective study

ObjectivesThe aim was to provide figures for drug shortages in France and describe their characteristics, causes and trends between 2012 and 2018.MethodsData from the national reporting system from the Agency...

FORMULATION A CIPROFLOXACIN HYDROCHLORIDE EXTENDED-RELEASE TABLET WITH COMBINATION OF HYDROXYPROPYL METHYLCELLULOSE (HPMC) K100M AND HYDROXYPROPYL METHYLCELLULOSE (HPMC) K4M BY DIRECT COMPRESSION METHOD

Objective: Ciprofloxacin hydrochloride tablets which are not extended-release will produce non-constant drug levels in the blood. This study aimed to overcome this problem by making ciprofloxacin hydrochloride extended-release tablets with a combination of hydroxypropyl methylcellulose (HPMC) K100M and hydroxypropyl methylcellulose (HPMC) K4M by a direct compression method.&#x0D; Methods: The method in this study consisted of preformulation, formula design, manufacture of ciprofloxacin hydrochloride tablets, tablet print mass testing, IPC (In-Process Control) slow-release tablet mass print, IPC (In-Process Control) quality of slow-release tablet preparation, dissolution test, and statistical analysis. Preformulation was carried out aiming to determine the physical and chemical properties of active-excipient substances based on a certificate of analysis. This was done using a Fourier Transform Infrared (FT-IR) and UV-Vis spectrophotometer. Five kinds of ciprofloxacin hydrochloride tablet formulations were made using the direct pressing method with variations in the concentration of HPMC K100M and HPMC K4M. The ratio of percentage of HPMC K100M and HPMC K4M were F1 0,5%: 1%, F2 1%: 0,5%, F3 0,75%: 0,75%, F4 1%: 0%, F5 0%: 3%. Evaluation of tablet preparations (IPC control) included weight uniformity test, size uniformity test, hardness test, and friability test. The dissolution test was carried out for 2 h by hydrochloride acid 0,1 N pH 1.2 as (pH of gastric acid). Statistical analysis using Perfect Block Random Design (PBRD) method and further testing using the Newman-Keuls test was applied for the data obtained.&#x0D; Results: The test results with FTIR showed that ciprofloxacin hydrochloride used compared to ciprofloxacin hydrochloride BPFI is equivalent and has a purity index of 0.992739. Determination of the level of the active ingredient ciprofloxacin hydrochloride was carried out by measuring the absorbance of a 5 ppm sample solution at a wavelength of 276 nm. The percentage of absorbance of the solution is then calculated and the result obtained is 98.87%. The range of levels that have been set is 98%-102%. These test results were under those listed on the certificate of analysis. The results of the IPC test in the form of weight uniformity test, size uniformity test, hardness test, friability test, and uniformity of ciprofloxacin hydrochloride levels in the preparation, showed all data obtained fulfilling the requirements set by USP 36 convention (2013). The result from dissolution tablet test on 30, 60, and 120 min showed the release of active substance on F1 56.00 %, 67.76 %, and 87.57 %. F2 were 53.42 %, 65.16 %, and 91.44 %. F3 were 59.18 %, 72.15 %, and 91.20 %. F4 were 50.51 %, 70.70 %, and 95.29 %. F5 were 53.75 %, 69.55 %, and 92.05 %. Statistical analysis was applied for the data obtained. Dissolution results illustrated the level of active substances dissolved in the dissolution medium for 2 h or in other words the dissolution test results indicated the number of active substances from tablets that were released and enter the digestive tract and came in contact with body fluids.&#x0D; Conclusion: The dissolution test results as a basis of extended-release tablets showed all of the formulae met dissolution requirements of the United States Pharmacopeia (USP) 36 convention.

Defining daily doses and total doses for the measurement of antibiotic usage in Swiss pig production

A significant Antibiotic-Monitoring-System is essential to analyse the use of antibiotics and to a better understanding of trends in resistance development. In human and veterinary medicine, for example, a system based on defined daily and treatment doses (Defined Daily Dose: DDD and Defined Course Dose: DCD) is applied. These definitions can be used to estimate the number of treatment days and treatments with antimicrobial agents in a population. For veterinary medicine, the European Medicines Agency (EMA) has published the European values DDDvet and DCDvet in the farm animal sector. The aim of this study was to define Swiss daily and treatment doses (DDDch and DCDch) for the treatment of pigs and to compare them with the EMA values in order to investigate the differences between individually collected national doses and average international doses. For the comparison, the quotient of Swiss and European values was calculated and the influence of the application form of an active substance and the number of active substances contained in a preparation was investigated. One hundred and three veterinary preparations with 138 active substances were assigned a DDDch and DCDch value. A comparison with EMA values was possible for 118 active substances. The comparison showed median values of 0.91 for the daily doses and 0.90 for the treatment doses, so that the daily and treatment doses in Switzerland are lower than the corresponding EMA doses. Both the form of application (injection solutions: 1.00; premixes: 0.76; P=0.02) and the number of active substances in the preparation (one active substance: 1.00; two active substances: 0.76; three active substances: 0.43; each P.

Development of antifungal therapies using nanomaterials.

The number and diversity of chemical structures currently available as antibacterial drugs is much higher compared with the number of active substances in relation to pathogenic fungi. In this review we focus on nanotechnology approaches, which offer promising strategies to create nanoagents that possess broad-spectrum antifungal activity and might overcome mechanisms of antibiotic resistance. Special attention was given to magnetic nanoparticles and their ability to restrict fungal growth directly, which depends on surface chemistry and pathogen strains. We speculate that future developments of new antifungal methods will take advantage of the current knowledge of using of magnetic nanomaterials as anticancer agents based on their ability to induce hyperthermia and enhance photosensitizing processes.

Abstract 2969: Paracrine effect of the endothelium on prostate cancer cells

Abstract Prostate cancer (CaP) is the most commonly diagnosed cancer and the second leading cause of cancer deaths among males in the United States. Androgen deprivation therapy (ADT) is the standard treatment for advanced or metastatic CaP. However, during ADT, CaP progresses from an androgen-sensitive (AS-CaP) to a more aggressive, and eventually lethal, castration-resistant (CRPC) phenotype. There is evidence to suggest that the prostate tumor mass is under tight control of endothelial microvasculature due to an increase in angiogenesis by tumor cells. Nevertheless, now there is evidence to support that this influence is not one-directional and that the endothelial cells secrete a large number of active substances (angiocrine factors), which may directly or indirectly influence tumor growth and progression. However, the direct impacts of the endothelium on prostate tumor progression or the molecular mechanisms that are involved in this communication remain unclear. Here we investigated the potential influence of endothelium-derived paracrine factors on prostate cancer biology and the role of connexins in these interactions, since connexins play a major role in cell-cell communication and form a bidirectional signaling pathway to assemble gap junctions and alter cell behaviors. We measured the effect of conditioned media (CM) obtained from a primary culture of human endothelial cells isolated from umbilical vein (HUVEC) on viability, proliferation, migration and invasion of CaP cell lines (LNCaP, LNCaP-C4-2 and PC3) and in the metastatic potential by in vivo assays using co-injection of CaP cell with HUVEC or injection of CaP cells pre-incubated with CM from HUVEC in a zebrafish embryo model. Finally, we studied the expression and the role of connexins on this stimulation using pharmacological (GJIC inhibitors) approaches. All together, our results showed that CM from endothelial cell induces an increases in the viability and proliferation in all CaP cell lines (LNCaP, LNCaP-C4-2 and PC3) but only increases migration of the CRPC cell lines (LNCaP-C4-2 and PC3). We also observed in our in vivo model that endothelial cells either through cell-cell interaction or by paracrine communication increases the metastatic ability of the CaP cells. Moreover, the increase in viability and migration of CaP cells observed with CM from endothelial cells was blocked using inhibitors of gap junctions. Real-time PCR analyses detected an up-regulation of Cx43 mRNA after exposition to CM from endothelial cells. Our data suggest that angiocrine communication between endothelial cells and CaP cells increases proliferation and migration of more aggressive CaP cells which could be important for the acquisition of the aggressive phenotype of the disease, and this interaction could be mediated by Cx43. Delineation of such critical players may culminate in identifying therapeutic targets or biomarkers to counteract CaP, especially advanced CaP. Citation Format: Verónica Torres-Estay, Patricia Fuenzalida, Catalina Ascencio, Carla Cembrano, Daniela Carreño, Néstor Corro, Viviana Montecinos, Gareth Owen, Xavier Figueroa, Julio Amigo, Juan Carlos Saéz, Alejandro Godoy. Paracrine effect of the endothelium on prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2969. doi:10.1158/1538-7445.AM2017-2969

The Exposure of Honey Bees to Pesticide Residues in the Hive Environment with Regard to Winter Colony Losses

Abstract The present studies are the second part of the research project dedicated to finding the causes for increased winter mortality of honey bee colonies. The aim of this task was to investigate incidents of overwintered colonies′ death with regard to the potential interrelation to the exposure to pesticides. The samples of winter stores of bee bread and sugar food (honey or syrup processed by bees), beeswax and bees collected from apiaries with low and high rates of winter colony mortality were searched for acaricides used to control V. destructor and plant protection pesticides. The presence of acaricides used in apiculture has been detected in the 51% beeswax samples. The most abundant acaricide was tau-fluvalinate. The stores of bee bread and sugar food had a similar frequency of plant protection pesticide occurrence, ranging between 50-60%, but the number of active substances and their concentrations were substantially lower in sugar food samples. The most prevalent pesticides in pollen were fungicides (carbendazim and boscalid) and insecticides (acetamiprid and thiacloprid). Only a few pesticides were found in the several dead honey bees. The level of pesticide contamination (frequency, concentration, toxicity) of hive products and bees originating from apiaries with both a high and low winter colony survival rates, was similar, which created a similar extent of risk. Although the multiple varroacides and pesticides were present in the hive environment we not found unequivocal links between their residues and high winter colony mortality.

&lt;strong&gt;Mites (Acari) important in different agroecosystems and their control in Romania*&lt;/strong&gt;

Mite problems in different agroecosystems in Romania are presented. Of all phytophagousmites known in the country, four species are found on a wide range of crops, with the two-spotted spider mite, Tetranychus urticae Koch, and the broad mite, Polyphagotarsonemus latus (Banks), being the most important. The broad mite is difficult to control, but acaricides registered in Romania have provided effective control of this species. Reduction of highly toxic pesticide residues in the environment has been considered important in the country. That could be approached by first reducing the amount of pesticides applied on agricultural land, and second, by finding new pesticides with less toxic active ingredients. This has resulted in reduced numbers of the main groups of pesticides, commercial products and number of active substances. The number of available commercial products varied from12 in 1972–1979 to five in 1980–1989, ten in 1990–1996, four in 1997–2004 and six in 2010, based on five active ingredients. The causes of the decreasing numbers of acaricide products or active ingredients were the reduced availability of several active ingredients due to toxicological or environmental reasons and the high registration cost. Only three acaricides (Envidor 240 SC, Nissorun 10WP and Omite 570 EC) and one insecticide/acaricide (Seizer 10 EC) are at present commonly used in Romanian agriculture.At the same time, from the economic point of view, biological control is impractical if not impossible to be applied in commercial crop production under Romanian economical conditions of farmers in absence of subsidies. EU and Romanian policies are discussed.

Pesticide residues intake of French adults under increased consumption of fresh fruits and vegetables – A theoretical study

The increase of fresh vegetable and fruit (FVF) intake could contribute to the prevention of obesity and several major pathologies and thus represents a major public health goal in industrial countries. Nutritional recommendations for increased consumption of FVF could lead to ingestion of unwanted amounts of pesticides. This study was undertaken to evaluate theoretical exposure of French adults to pesticide residues under increasing amounts of FVF intake. Balanced menus with 200 – 400 – 600 – 800 and 1200 g FVF/day were established. Amounts of active substances brought by every FVF vector, at the maximum residue level (MRL) were summed up to determine the intake for each active substance. Values were compared to the Acceptable Daily Intake (ADI) to point out any potential over exposure. A maximalistic approach was adopted and no reducing factor due to processing was taken into account. It was found that under minimal recommended consumption of fruit and vegetables (400 g/d), no active substance reached the ADI, but 18 vs 144 were over 10% of the ADI. Raising FVF to 600 g/d increased the number of active substances over 10 % of the ADI to 24, but again in no case was the ADI exceeded. Doubling the intake to 800 g/d gives values over the ADI for 2 active substances only (cyhexatin and thirame). It was concluded that the increase in fruit and vegetables up to 800 g per day should not expose adults over the ADIs for a majority of authorized pesticides. In this regard, residues levels of ten active substances in fruit and vegetables should deserve particular attention.

Effective Treatment of Patients in a Deep Salvage Situation with "Non-Active HAART": Experiences with the Expert Advice System RADATA

Clinical studies suggest expert recommendations as a possibility to optimize highly active antiretroviral therapy (HAART) in patients with multi-drug resistant virus strains. An online system (RADATA) has been developed to provide expert advice for the drug therapy of HIV-infected patients. To evaluate the efficacy of expert-advice-guided HAART switches in patients with triple-class failure. Virological and immunological outcome of patients having undergone at least three prior ART regimens, including nucleoside inhibitor (NRTI), nonnucleoside reverse transcriptase inhibitor (NNRTI), and protease inhibitor (PI) use, were analyzed. Changes in HIV-RNA and CD4-cell count were evaluated every 3 months. 183 patients with a median baseline viral load of 3.90 log copies/ml (1.88-6.54 log) and a CD4-cell count of 298 c/ll (5-910 c/ll) were eligible for analysis. The patients had a median of seven prior ART regimens and a treatment duration of 83 months. A median of three (range 0-8) NRTI-, two (0-7) thymidine-associated (TA), one (0-4) NNRTI-, and three (0-13) PI-associated resistance mutations were present at baseline. Despite available resistance analyses and expert recommendations, 66% (n = 119) of the patients started a new ART regimen without any active drugs according to the resistance analysis. The HIV-RNA declined by a median of 0.61 log and 0.92 log after 12 and 24 months, respectively, while the CD4-cell count rose by a median of +9 c/microl and +25 c/microl during this period. No significant differences related to number of prior regimens or number of active substances used could be found. Despite extensive pre-treatment and multiple resistances against prescribed HAART, our patients demonstrated a decline in viral load and a stable CD4-cell count over the observation period. We conclude that the activity of antiretroviral regimens is not exclusively explained by the current algorithms used for estimating antiretroviral drug activity.