Elizabeth de Souza Nascimento

Informações toxicológicas de alguns fitoterápicos utilizados no Brasil

ABSTRACT Toxicological information of some herbal medicinesused in Brazil Herbal medicines have been used with therapeuticalpurposes for thousands of years. Its popular use hasbeen transmitted across generations and is described inthe pharmacopeas. Since the development of organicchemistry, it became possible to obtain pure substancesby isolating active substances from plants, among them,digoxine and morphine, resulting in lack of interest forresearch of substances originated from vegetals.However, from the 1980´s onwards, new methods forisolating active substances were developed and itbecame possible to identify substances in complexsamples such as vegetal extracts, restoring the interestfor vegetally-originated compounds that could be usedas prototypes for the development of new drugs.Nowadays, in spite of the growing importance of herbalmedicines, relatively few studies have been performed toprove efficacy and safety, while many plants are still usedon the basis of popular well-established use. Theobjective of this paper is to assess the availability of pre-clinical toxicity data for ten medicinal plants marketedas herbal medicines in Brazil, in major databases andpublic sources of information. Few data were foundregarding pre-clinical toxicity on the ten medicinalplants surveyed, but, in general, experiments in animalsshowed low acute, sub-acute and chronical toxicity anddid not show mutagenic or teratogenic toxicity.UNITERMS: Toxicological information. Herbalmedicines. Medicinal plants. Pre-clinical toxicity.

Adverse Effects of Plant Food Supplements and Plants Consumed as Food: results from the Poisons Centres-Based PlantLIBRA Study

Plant food supplements (PFS) are products of increasing popularity and wide‐spread distribution. Nevertheless, information about their risks is limited. To fill this gap, a poisons centres‐based study was performed as part of the EU project PlantLIBRA. Multicentre retrospective review of data from selected European and Brazilian poisons centres, involving human cases of adverse effects due to plants consumed as food or as ingredients of food supplements recorded between 2006 and 2010. Ten poisons centres provided a total of 75 cases. In 57 cases (76%) a PFS was involved; in 18 (24%) a plant was ingested as food. The 10 most frequently reported plants were Valeriana officinalis, Camellia sinensis, Paullinia cupana, Melissa officinalis, Passiflora incarnata, Mentha piperita, Glycyrrhiza glabra, Ilex paraguariensis, Panax ginseng, and Citrus aurantium. The most frequently observed clinical effects were neurotoxicity and gastro‐intestinal symptoms. Most cases showed a benign clinical course; however, five cases were severe. PFS‐related adverse effects seem to be relatively infrequent issues for poisons centres. Most cases showed mild symptoms. Nevertheless, the occurrence of some severe adverse effects and the increasing popularity of PFS require continuous active surveillance, and further research is warranted. Copyright

Pharmacokinetics of tetracycline in plasma, synovial fluid and milk using single intravenous and single intravenous regional doses in dairy cattle with papillomatous digital dermatitis.

The purpose of this study was to compare the pharmacokinetics of tetracycline in plasma, synovial fluid, and milk following either a single systemic intravenous (i.v.) injection or a single i.v. regional antibiosis (IVRA) administration of tetracycline hydrochloride to dairy cattle with papillomatous digital dermatitis (PDD). To this end, plasma and synovial fluid tetracycline concentrations were compared with the minimal inhibitory concentration (MIC) values of the major bacteria, which are known to cause digital diseases and thus assess its efficacy in PDD. Residual tetracycline concentrations in milk from cows treated by both methods were also determined. Twelve Holstein cows with various stages of PDD were randomly assigned to two groups of six animals. Group 1 received a single systemic i.v. injection of 10 mg/kg of tetracycline hydrochloride. Group 2 received 1000 mg of tetracycline hydrochloride by IVRA of the affected limb. Blood, synovial fluid and milk samples were taken prior to tetracycline administration (time 0 control), and then at 22, 45 and 82 min, and 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 h following drug administration. Tetracycline concentrations were determined by high-performance liquid chromatography. Mean tetracycline plasma and milk concentrations in Group 1 were higher than Group 2. The opposite was observed for synovial fluid concentrations. Group 2 synovial fluid concentrations were higher than the MIC value over 24 h for the bacteria most frequently responsible for claw disease. Compared with i.v. administration, IVRA administration of tetracycline produced very high synovial fluid and low plasma and milk concentrations.

Validação de método para determinação de resíduos dos antibióticos oxitetraciclina, tetraciclina, clortetraciclina e doxiciclina, em leite, por cromatografia líquida de alta eficiência

Tetracyclines are antimicrobial agents used in dairy cattle to treat infection diseases, as mastitis and also as additives in animal food to improve feed efficiency and growth. The use of tetracyclines can result in the presence of residue of these antimicrobials in the milk, especially if they are not used according to the label directions and if the minimum period of their elimination is not respected. The presence of antibiotic residues in the milk interferes in the dairy industrial process diminishing starter culture growth used in the yogurt and cheese production, causing strong economic loss. Antibiotic residue in the consumer milk may represent risk to the human health, allows allergic reactions in sensitive human beings, disorders of the intestinal flora damaging its local protection action and provides antibiotic resistance development. The objective of this study was to validate the multiresidue method to determine the oxytetracycline, tetracycline, chlortetracycline and doxycycline in milk by acidic desproteinization extraction and to identify and quantify them by high performance liquid chromatography with photo-diode array detector. The method presented detection limit and quantification limit respectively of 37,5 and 50 ng/mL, linearity from 50 to 1600 ng/mL and correlation coefficient of 0,9996, 0,9994, 0,9996 and 0,9996 to the oxytetracycline, tetracycline, chlortetracycline and doxycycline respectively;and recovery between 66,6 and 89,2%, with good precisions and accurancy.

Comparação entre as administrações tópica e sistêmica de oxitetraciclina no tratamento de vacas com dermatite digital papilomatosa

The efficacy of topical versus systemic treatment with oxytetracycline for papillomatous digital dermatitis (PDD) in dairy cows was compared. Antimicrobial residues in milk and their concentrations in synovial fluid and plasma were analysed. Sixteen lactating Holstein cows with PDD lesions were topically treated with oxytetracycline powder (group 1) or long-acting oxytetracycline (group 2). Plasma, synovial fluid, and milk samples were collected in the following moments: M0 (before treatments); at six hours after treatments (M1), and at 12-hour intervals until 264 hours after treatments (M23). Lameness score and lesion size were evaluated. Analysis of oxytetracycline concentration was performed by high-performance liquid chromatography (HPLC). Cows in group 1 showed reduced lesion size and lameness score when compared to cows in group 2. None of the plasma, synovial fluid, or milk samples collected from cows in group 1 were positive to oxytetracycline. However, violative antimicrobial residues were detected in milk samples collected from cows in group 2, from M1 until M23. Topical application of oxytetracycline powder was an efficient treatment for PDD with no risk of violative antimicrobial residues in milk or increases its concentration in plasma or synovial fluid. The systemic administration of oxytetracycline was inefficient to treat PDD and caused violative residues in milk.

The introduction of the Salmonella/microsome mutagenicity assay in a groundwater monitoring program

The objective of this study was to verify the possible inclusion of the Salmonella/microsome mutagenicity assay in a groundwater monitoring program as a complementary assay to assess water quality. Groundwater samples belonging to seven wells from different types of aquifers were analyzed. Three different methods for sample preparation were used: membrane filtration; liquid-liquid and XAD-4 extraction. The filtered samples were tested using TA98, TA100, YG1041 and YG1042 and the water extracts only with TA98 and TA100. No mutagenic activity was observed in any of the 16 filtered samples tested. Out of the 10 samples analyzed using XAD-4 extraction, five showed mutagenic activity with potency ranging from 130 to 1500 revertants/L. Concerning the liquid-liquid extraction, from the 11 samples analyzed, 3 showed mutagenicity. The XAD-4 extraction was the most suitable sample preparation. TA98 without S9 was found to be the most sensitive testing condition. The wells presenting water samples with mutagenic activity belonged to unconfined aquifers, which are more vulnerable to contamination. The data suggest that Salmonella/microsome assay can be used as an efficient screening tool to monitor groundwater for mutagenic activity.

Occupational exposure profile of Pb, Mn, and Cd in nonferrous Brazilian sanitary alloy foundries.

In addition to the primary components of alloys, approximately 5% of the formulation may contain other metals, including lead (Pb), cadmium (Cd), arsenic, manganese (Mn), iron, phosphorus, and nickel. Workers in the foundries are exposed to several compounds; therefore, it is important to assess the levels of injury that may reflect an additive, synergistic, or antagonistic effect caused by these compounds. The mean values of the environmental evaluation of the facilities range from 16.65 to 40.31 µg m−3 for Pb, 0.99 to 1.73 µg m−3 for Cd, and 0.91 to 1.70 µg m−3 for Mn. The mean values of the metal concentrations for furnace, mold, melting, and automatic melting activities range from 15.37 to 19.26 µg m−3 for Pb, 7.07 to 9.14 µg m−3 for Cd, and 8.83 to 16.00 µg m−3 for Mn. Biological samples were divided into two groups: control (n = 38) and exposed (n = 45). The obtained data are3.41 ± 3.40 and 14.89 ± 7.82 µg dL−1 for Pb, 0.90 ± 0.80 and 1.91 ± 1.90 µg g−1 creatinine for Cd, and 0.51 ± 0.40 and 3.17 ± 1.93 µg g−1 creatinine for Mn. Statistical analysis showed significant differences (p < 0.05). Positive linear correlations were established between metal concentrations in the air and the biological matrixes: Pb (r = 0.68; p < 0.001), Cd (r = 0.81; p = 0.17), and Mn (r = 0.12; p < 0.03). Regression analysis showed that professional activities can interfere with element exposure profiles in occupational settings. The analysis in the event of exposure to metals in these companies allowed investigating whether the simultaneous exposure leads to biological damage even if the levels of the compounds are within the exposure limits that are considered to be safe.

Aspectos analíticos do controle da dopagem de agentes anabolizantes em urina de atletas: avaliação de critérios de positividade

The use of anabolic androgenic steroids (AAS) in sports is in a constant increase among professionals athlets and amateurs. These substances were banned by the International Olimpic Committee and the doping control of this steroids are to be performed analysing biological samples taken from this athletes using gas cromatography coupled with mass spectrometry (GC/MS). This paper evaluates 15 AAS by means of liquid extration and subsequent GC/MS identification. Three of these AAS were also quantified. Correlation criteria among the AAS most characteristic ions were stablished for the evidence of positive samples: when comparing these ions to theose in the reference spectrum, the ion with the highest abundance is set as 100%. The relative intensity, compared to the same ion in the reference spectrum, higher than 20%, can alter up to 30%; between 10 e 20%, can alter up to 50% and lower than 10% can alter up to 90%. By using these criteria, it was possible to confirm the presence of AAE in eight urine samples taken from athletes who claimed the use of these compounds. It was also evident the importance of applaying positiviness criteria when analysing the presence of these substances in biological samples.

Chemical waste risk reduction and environmental impact generated by laboratory activities in research and teaching institutions

The environmental impact caused by teaching and research with regard to chemical waste is of increasing concern, and attempts to solve the issue are being made. Education and research-related institutions, in most laboratory and non-laboratory activities, contribute to the generation of small quantities of waste, many of them highly toxic. Of this waste, some is listed by government agencies who are concerned about environmental pollution: disposal of acids, metals, solvents, chemicals and toxicity of selected products of synthesis, whose toxicity is often unknown. This article presents an assessment of the problem and identifies possible solutions, indicating pertinent laws, directives and guidelines; examples of institutions that have implemented protocols in order to minimize the generation of waste; harmonization of procedures for waste management and waste minimization procedures such as reduction, reuse and recycling of chemicals.

Determinação de tetraciclina em líquido sinovial de vacas com doença podal

Lameness in cattle is, as a rule, accompanied by infection in the wounded area. Many antimicrobial agents of wide spectrum are used in this therapy, being the concentration of the active principle of paramount importance in the treatment. One of the most used antibiotics is the tetracycline family, having as main representants oxitetracycline and tetracycline due to their treatment success. Therefore, the present work aims the development of an analytical method which allows the determination of tetracycline by High Pressure Liquid Chromatography in sinovial fluid of dairy cows, with lameness in foot, post-administration of antibiotic by intravenous via. The analytical method presented detection and quantification limits in sinovial fluid of 38 and 50 ng/mL, respectively. Recovery of low, medium and high concentrations were higher than 75%. The method presented linearity in the dynamic range evaluated (50-15.000 ng/mL). Precision and accuracy to the low, average and high concentrations were considered suitable to perform the analyses. Tmax and Cmax of tetracycline in sinovial liquid of dairy cows with lameness in foot, after intravenous administration were 1.37h and 3471.57ng/mL, respectively.