Anticholinesterase activity of ß-carboline-1, 3, 5-triazine hybrids

Abstract The ß-carboline-1,3,5-triazine hydrochlorides 8-13 were evaluated in vitro against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The analysed compounds were selective to BuChE, with IC50 values in the range from 1.0-18.8 µM being obtained. The N-{2-[(4,6-dihydrazinyl-1,3,5-triazin-2-yl)amino]ethyl}-1-phenyl-ß-carboline-3-carboxamide (12) was the most potent compound and kinetic studies indicate that it acts as a competitive inhibitor of BuChE. Molecular docking studies show that 12 strongly interacts with the residues of His438 (residue of the catalytic triad) and Trp82 (residue of catalytic anionic site), confirming that this compound competes with the same binding site of the butyrylthiocholine

Evaluation of the cytotoxic and genotoxic effects by melamine and cyanuric acid co-exposure in human embryonic kidney 293 cells

The melamine and cyanuric acid (CA) complex has been suggested to cause the toxic effects observed in melamine-contaminated food or milk. However, the cytotoxic and genotoxic effects of co-exposure to melamine and CA are not fully clear. Therefore, the cytotoxic effects of melamine and CA were first examined by co‐exposure in human kidney 293 cells using the MTT assay. During a 24-h period for the three concentrations tested (0.5, 1, and 5 mg/mL), neither melamine nor CA alone showed significant toxic effects on 293 cells at 0.5 mg/mL, while higher concentrations led to decreased in cell viability. However, co-exposure to several combinations of melamine and CA [100:1, 10:1, 1:10, and 1:100 (v:v), at a final concentration of 0.5 mg/mL] did cause cytotoxicity with higher levels of CA leading to higher cytotoxicity. By contrast, while neither melamine nor CA alone induced phosphorylated-H2AX (γH2AX) foci formation, melamine and CA at a 100:1 ratio induced γH2AX foci 24 h post-treatment. The alkaline comet assay also revealed the presence of DNA damage following melamine and CA co-exposure. In vivo assay also revealed the presence of melamine-CA complex in the kidney. These data indicated that the cytotoxic and genotoxic effects of melamine and CA co-exposure differ from those of melamine or CA alone.

Levetiracetam and lamotrigine effects as mono- and polytherapy on bone mineral density in epileptic patients / Efeitos do levetiracetam e lamotrigina, em mono e politerapia, na densidade mineral óssea de pacientes epilépticos

ABSTRACT The purpose of this study was to determine the effect of lamotrigine (LTG) and levetiracetam (LEV) as mono- and polytherapy on biochemical markers of bone turnover and bone mineral density in Egyptian adult patients with epilepsy. Methods Forty-eight patients were divided into four groups: two received monotherapy of either LTG or LEV, and the other two groups received polytherapy comprising (valproate [VPA] + LTG or VPA + LEV). Thirty matched healthy participants were included in the study. Participants completed a nutritional and physical activity questionnaire. Biochemical markers of bone and mineral metabolism and bone mineral density of the lumbar spine were measured at baseline and at six months. Results In the LEV monotherapy group, the bone formation markers showed a significant decrease in serum alkaline phosphatase and serum osteocalcin levels while the bone resorption marker showed a significant increase in urinary deoxypyridinoline levels. After six months of treatment, bone mineral density showed a significant decrease in all treated groups, while among monotherapy groups, this significant decrease was more prevalent in the LEV monotherapy group compared with the LTG monotherapy group. Furthermore, there was significant negative correlation between urinary deoxypyridinoline levels and bone mineral density in the LEV monotherapy group. Conclusion Using new generation antiepileptics, LEV monotherapies and polytherapy showed harmful effects on bone but LTG did not.

RESUMO O objetivo deste estudo foi determinar o efeito da lamotrigina (LTG) e levetiracetam (LEV) como mono e politerapia em marcadores bioquímicos de remodelação óssea e densidade mineral óssea em pacientes adultos egípcios com epilepsia. Métodos Quarenta e oito pacientes foram divididos em quatro grupos: dois grupos receberam monoterapia de LTG ou LEV e os outros dois grupos receberam politerapia (valproato [VPA] + LTG ou VPA + LEV). Trinta participantes saudáveis controle foram incluídos no estudo. Os participantes preencheram um questionário nutricional e de atividade física. Marcadores bioquímicos do metabolismo ósseo e mineral e densidade mineral óssea da coluna lombar foram medidos no início e aos seis meses. Resultados No grupo de monoterapia LEV, os marcadores de formação óssea mostraram uma diminuição significativa nos níveis séricos de fosfatase alcalina e osteocalcina sérica, enquanto o marcador de reabsorção óssea mostrou um aumento significativo nos níveis de desoxipiridinolina urinária. Após seis meses de tratamento, a densidade mineral óssea mostrou uma diminuição significativa em todos os grupos tratados, enquanto entre os grupos de monoterapia, esta diminuição significativa foi mais prevalente no grupo de monoterapia LEV em comparação com o grupo de monoterapia LTG. Além disso, houve correlação negativa significativa entre os níveis de desoxipiridinolina urinária e densidade mineral óssea no grupo de monoterapia LEV. Conclusão Utilizando antiepilépticos de nova geração, as monoterapias LEV e a politerapia mostraram efeitos prejudiciais no osso, mas a LTG não.

Triazine Compound as Copolymerized Antibacterial Agent in Adhesive Resins

Abstract The aim of this study was to formulate and evaluate an experimental adhesive resin with the addition of 1,3,5-triacryloylhexahydro-1,3,5-triazine at different concentrations. Experimental adhesive resins were obtained by mixing 50% wt bisphenol A glycol dimethacrylate (BisGMA), 25% wt triethylene glycol dimethacrylate (TEGDMA), 25% wt 2-hydroxyethyl methacrylate (HEMA) and photoinitiator system. The triazine compound was added in 1, 2.5 and 5% wt to a base adhesive resin and one group remained with no triazine as control group. The experimental adhesive resins were analyzed for antibacterial activity (n=3), degree of conversion (n=3) and softening in solvent (n=3). Data distribution was evaluated by Kolmogorov-Smirnov test, paired t test, one-way ANOVA and Tukey’s with a 0.05 level of significance. All groups with added triazine compound showed antibacterial activity against Streptococcus mutans (p<0.05). All groups achieved more than 70% degree of conversion, but there was no difference in this chemical property (p>0.05). The initial Knoop hardness was higher in 2.5 and 5% wt groups (p<0.05) and both groups present lower percentage variation of Knoop hardness after solvent degradation. The present study formulated an antibacterial adhesive resin with a non-releasing agent able to copolymerize with the comonomeric blend, improving the restorative material’s properties.

Resumo O objetivo desse estudo foi desenvolver e avaliar a adição de 1,3,5-triacryloylhexahydro-1,3,5-triazine a uma resina adesiva experimental em diferentes concentrações. Resinas adesivas experimentais foram obtidas a partir da mistura de 50% em peso de bisphenol A glycol dimethacrylate (BisGMA), 25% em peso de triethylene glycol dimethacrylate (TEGDMA), 25% em peso de hidroxietil metacrilato (HEMA) e sistema fotoiniciador. O composto de triazina foi adicionado em proporções de 1; 2,5 e 5% em peso a resina adesiva base e um grupo permaneceu sem a adição do composto de triazina como grupo controle. As resinas adesivas experimentais foram analisadas por atividade antibacteriana (n=3), grau de conversão (n=3) e degradação em solvente (n=3). A distribuição dos dados foi avaliada por teste de Kolmogorov-Smirnov, teste t pareado, ANOVA de uma via e Tukey, considerando nível de significância de 5%. Todos os grupos com adição de composto de triazina demonstraram atividade antibacteriana contra Streptococcus mutans (p<0,05). Todos os grupos atingiram mais de 70% de grau de conversão, mas não houve diferença estatística para essa propriedade química (p>0,05). A dureza Knoop inicial foi maior para os grupos com 2,5 e 5% de triazina (p<0,05) e ambos os grupos apresentaram menor variação percentual de dureza Knoop após degradação em solvente. No presente estudo, foi produzida uma resina adesiva antibacteriana com agente sem liberação para o meio, capaz de copolimerizar com a blenda comonomérica, melhorando as propriedades do material restaurador.

Identifying the incidence of rash, Stevens-Johnson syndrome and toxic epidermal necrolysis in patients taking lamotrigine: a systematic review of 122 randomized controlled trials

ABSTRACT Lamotrigine is an antiepileptic drug used for the treatment of epilepsy, bipolar disorder and numerous off-label uses. The development of rash significantly affects its use. The most concerning of these adverse reactions is Stevens-Johnson syndrome/toxic epidermal necrolysis. We performed a systematic review of randomized controlled trials using lamotrigine as a monotherapy to quantify the incidence of cutaneous reactions, particularly Stevens-Johnson syndrome/toxic epidermal necrolysis. Of a total of 4,364 papers regarding lamotrigine, 122 studies met our inclusion and exclusion criteria. In total, 18,698 patients were included with 1,570 (8.3%) of patients experiencing an adverse dermatologic reaction. The incidence of Stevens-Johnson syndrome/toxic epidermal necrolysis was 0.04%.

Efficacy of treatments with toltrazuril 7. 5% and lasalocid sodium in sheep naturally infected with Eimeria spp / Eficácia de tratamentos com toltrazuril 7, 5% e lasalocida sódica em ovinos naturalmente infectados com Eimeria spp

Abstract The objective of this study was to evaluate the efficacy of an experimental formulation of toltrazuril 7.5% + Trimix™ on a naturally acquired infection of Eimeria spp. in suckling lambs kept on pasture and, in another trial, evaluate the comparative efficacy between lasalocid and toltrazuril 7.5% + Trimix™ in newly weaned sheep under feedlot conditions that had been naturally infected with Eimeria spp. In the first experiment, 30 suckling lambs were divided into two groups: A - treated with toltrazuril 7.5% + Trimix™ and B- control. In experiment 2, 30 weaned sheep were divided into three groups: I - treated with toltrazuril 7.5% + Trimix™, II - treated with lasalocid and III - control. Treatment group A showed an efficacy of 90, 99.4 and 87.3% on days 5, 10 and 20, respectively. Treatment group I had an efficacy of 98.2, 92.6 and 94.5%, while group II had an efficacy of 72.7, 81.6 and 95.9% on days 7, 21 and 42, respectively. Eight Eimeria species were identified; E. ovinoidalis was the most common. Treatment with the toltrazuril 7.5% +Trimix ™ formulation was effective against Eimeria spp. in suckling lambs in field conditions and lambs weaned in under feedlot conditions.

Resumo O objetivo deste estudo foi avaliar a eficácia de uma formulação experimental de toltrazuril 7,5% + Trimix™ em cordeiros mantidos em pastagem com infecção naturalmente adquirida por Eimeria spp. e, em outro teste, a eficácia comparativa entre lasalocida sódica e toltrazuril 7,5% + Trimix™ em ovinos recém-desmamados, naturalmente infectados com Eimeria spp. em condições de confinamento. No primeiro experimento, 30 cordeiros lactantes foram divididos em dois grupos: A - tratados com toltrazuril 7,5% + Trimix™; e B - controle. No experimento 2, 30 ovinos desmamados foram divididos em três grupos: I - tratados com toltrazuril 7,5% + Trimix™; II - tratados com lasalocida sódica; e III - controle. O grupo A (tratado) obteve uma eficácia de 90, 99,4 e 87,3% nos dias 5, 10 e 20, respectivamente. O grupo I teve eficácia de 98,2, 92,6 e 94,5%, enquanto o grupo II teve uma eficácia de 72,7, 81,6 e 95.9% nos dias 7, 21 e 42, respectivamente. Foram identificadas oito espécies de Eimeria sendo E. ovinoidalis a mais comum. O tratamento com a formulação de toltrazuril 7,5% + Trimix™ foi eficaz contra Eimeria spp. em cordeiros em lactação em condições de campo e em ovinos desmamados em confinamento.

Effects of vardenafil on the kidney of Wistar rats submitted to acute ischemia and reperfusion

PURPOSE: To investigate the effect of vardenafil in kidney of rats submitted to acute ischemia and reperfusion. METHODS: Twenty-eight rats were randomly distributed into two groups. Right nephrectomy was performed and the vardenafil group received vardenafil solution (at a concentration of 1 mg/ml in 10 mg/kg) while the control group received 0.9% saline solution (SS) one hour prior to the ligature of the left renal pedicle. After one hour of ischemia, animals were submitted to twenty-four hours of reperfusion, followed by left nephrectomy. The kidney's histological parameters evaluated on the study included vacuolar degeneration and tubular necrosis. Apoptosis was assessed by immunohistochemistry for cleaved caspase-3 using the point-counting and digital methods (Cytophotometry). Also, a biochemical analysis for creatinine was conducted. RESULTS: There were statistically significant differences between groups only with regards to the vacuolar degeneration parameter and to the cleaved caspase-3 digital method. CONCLUSION: Vardenafil showed a protective effect on the kidney of rats subjected to acute ischemia and reperfusion in this model .

The effects of vardenafil and pentoxifylline administration in an animal model of ischemic colitis

OBJECTIVES: Vardenafil enhances dilatation of vascular smooth muscle and inhibits platelet aggregation. The purpose of this study was to evaluate the clinical effects of vardenafil and pentoxifylline administration in an experimental model of ischemic colitis. METHODS: Forty female Wistar albino rats weighing 250-300 g were randomized into five experimental groups (each with n = 8) as follows:1) a sham group subjected to a sham surgical procedure and administered only tap water; 2) a control group subjected to a standardized surgical procedure to induce ischemic colitis and administered only tap water; 3) and 4) treatment groups subjected to surgical induction of ischemic colitis followed by the postoperative administration of 5 mg/kg or 10 mg/kg vardenafil, respectively; and 5) a treatment group subjected to surgical induction of ischemic colitis followed by postoperative administration of pentoxifylline at 50 mg/kg/day per day as a single dose for a 3-day period. All animals were sacrificed at 72 h post-surgery and subjected to relaparotomy. We scored the macroscopically visible damage, measured the ischemic area and scored histopathology to determine the severity of ischemia. Tissue malondialdehyde levels were also quantified. RESULTS: The mean Gomella ischemic areas were 63.3 mm2 in the control group; 3.4 and 9.6 mm2 in the vardenafil 5 and vardenafil 10 groups, respectively; and 3.4 mm2 in the pentoxifylline group (p = 0.0001). The mean malondialdehyde values were 63.7 nmol/g in the control group; 25.3 and 25.6 nmol/g in the vardenafil 5 and vardenafil 10 groups, respectively; and 22.8 nmol/g in the pentoxifylline group (p = 0.0001). CONCLUSION: Our findings indicate that vardenafil and pentoxifylline are effective treatment options in an animal model of ischemic colitis. The positive clinical effects produced by these drugs are likely due to their influence on the hemodynamics associated ...

PDE5 Inhibitor Treatment Persistence and Adherence in Brazilian Men: Post-hoc Analyses from a 6-Month, Prospective, Observational Study

Purpose Characterize persistence and adherence to phosphodiesterase type - 5 inhibitor (PDE5I) on-demand therapy over 6 months among Brazilian men in an observational, non-interventional study of Latin American men naïve to PDE5Is with erectile dysfunction (ED). Materials and Methods Men were prescribed PDE5Is per routine clinical practice. Persistence was defined as using ≥ 1 dose during the previous 4 - weeks, and adherence as following dosing instructions for the most recent dose, assessed using the Persistence and Adherence Questionnaire. Other measures included the Self - Esteem and Relationship (SEAR) Questionnaire, and International Index of Erectile Function (IIEF). Multivariate logistic regression was used to identify factors associated with persistence/adherence. Results 104 Brazilian men were enrolled; mean age by treatment was 53 to 59 years, and most presented with moderate ED (61.7%). The prescribed PDE5I was sildenafil citrate for 50 (48.1%), tadalafil for 36 (34.6%), vardenafil for 15 (14.4%), and lodenafil for 3 patients (2.9%). Overall treatment persistence was 69.2% and adherence was 70.2%; both were numerically higher with tadalafil (75.0%) versus sildenafil or vardenafil (range 60.0% to 68.0%). Potential associations of persistence and/or adherence were observed with education level, ED etiology, employment status, and coronary artery disease. Improvements in all IIEF domain scores, and both SEAR domain scores were observed for all treatments. Study limitations included the observational design, brief duration, dependence on patient self - reporting, and limited sample size. Conclusion Approximately two-thirds of PDE5I-naive, Brazilian men with ED were treatment persistent and adherent after 6 months. Further study is warranted to improve long-term outcomes of ED treatment. .

Anticonvulsant profile of 2-ethylthio-7-methyl-4-(4-methylphenyl)pyrazolo[1, 5-a][1, 3, 5]triazine

This work evaluates the central nervous effects in ICR strain mice of 2-ethylthio-7-methyl-4-(4-methylphenyl)pyrazolo[1,5-a][1,3,5]triazine (MH4b1), a compound obtained by an efficient one-step reaction of S,S-diethyl 4-methylbenzoylimidodithiocarbonate with 5-amino-3-methyl-1H-pyrazole, in order to assess its neuro-pharmacological profile. The tests applied were: maximal electroshock seizure (MES), pentylenetetrazole (PTZ) seizures, forced swimming, plus maze, marble burying, sleeping time, rota-rod and catalepsy. In addition, MH4b1 binding to the benzodiazepine site of the GABA-A receptor and MH4b1 inhibition of monoamine oxidase (MAO) subtypes A and B were evaluated. MH4b1 showed anticonvulsant effects in a dose dependent manner (30-300 mg/kg, p.o.) against MES and inhibition of MAO-B (IC50: 24.5 µM) without activity at the benzodiazepine site. These data suggest that MH4b1 has anticonvulsant properties related to MAO-B inhibition.

Este trabalho avalia o efeito do 2-etiltio-7-metil-4-(4-metilfenil)pirazol[1,5-a][1,3,5]triazina (MH4b1) no sistema nervoso central de camundongos ICR. O MH4b1 foi obtido por a reação de 4-metilbenzoilimidoditiocarbonato de S,S-dietil e 5-amino-3-metil-1H-pirazol em uma única etapa. O perfil neurofarmacológico foi realizado por testes de convulsão induzida por eletrochoque (MES) e pentilenotetrazol (PTZ) e por testes de nado forçado, labirinto em cruz, esconder as esferas, sono barbitúrico, rota-rod e catalepsia. Também foi avaliada a união do MH4b1 ao o local de ligação de benzodiazepínicos do receptor GABA-A e a capacidade inibitória do MH4b1 sobre a monoaminoxidase (MAO) A e B. O MH4b1 mostrou efeito anticonvulsivante dependente da dose (30-300 mg) no teste do MES e apresentou atividade inibitória da MAO-B (CI50: 24.5 µM) sem interagir com o local de ligação de benzodiazepínicos do receptor. Os resultados sugerem que o MH4b1 tem atividade anticonvulsivante relacionada com a inibição da MAO-B.

Meningoencefalitis aséptica como manifestación de un síndrome de rash con eosinofilia y síntomas sistémicos asociados a drogas por lamotrigina / Aseptic meningoencephalitis as infectation of a sindrome of rash with eosinophilia and systemic symptoms associated with drugs caused by lamotrigine

Aseptic meningitis (AM) is defined by the presence of cerebrospinal fluid findings consistent with meningitis, without achieving the isolation of a bacterium that produces it. Drugs are one of the diverse causes of AM. Drugs frequently associated with AM include immunoglobulin's, nonsteroidal anti-inflammatory, antibiotics, and aromatic anticonvulsants. When AM is part of a systemic response accompanying a cutaneous manifestation it may be a DRESS (Drug Rash with Eosinophilia and Systemic Symptoms), considered a serious adverse reaction to drugs. Lamotrigine is a non-aromatic anticonvulsant widely used for the treatment of epilepsy and bipolar disorder, which has been associated with AM. We report a case of aseptic meningoencephalitis as a manifestation of DRESS associated to lamotrigine.

La meningitis aséptica (MA) se define por la presencia de hallazgos en el líquido cefalorraquídeo compatibles con una meningitis, sin que se logre aislar una bacteria que la produzca. Las causas de MA son diversas, entre las que se encuentran las drogas. Entre los fármacos que más frecuentemente se han asociado a MA, se encuentran los antiinflamatorios no esteroidales, antibióticos, inmunoglobulinas y anticonvulsivantes aromáticos. Cuando la MA forma parte de una respuesta sistémica que acompaña a una manifestación cutánea, puede tratarse de un rash con eosinofilia y síntomas sistémicos asociado a drogas (DRESS, acrónimo derivado del inglés DrugRash with Eosinophilia and Systemic Symptoms), considerada una reacción adversa grave a medicamentos. La lamotrigina es un anticonvulsivante no aromático ampliamente utilizado para el tratamiento de la epilepsia y el trastorno bipolar que ha sido asociada con MA. Comunicamos un caso de meningoencefalitis aséptica como manifestación de DRESS asociado al uso de lamotrigina.

Inibidores da fosfodiesterase do tipo 5 e perda auditiva neurossensorial subita / Phosphodiesterase Type 5 Inhibitors and sudden sensorineural hearing loss

O uso de inibidores da fosfodiesterase do tipo 5 como sildenafil, vardenafil e tadalafil tem aumentado atualmente e alguns destes pacientes vêm apresentando perda auditiva neurossensorial súbita. OBJETIVO: Apresentar dois casos de pacientes que apresentaram surdez súbita em uso eventual do medicamento e revisar estudos sobre o uso de inibidores da fosfodiesterase do tipo 5 e surdez súbita. MÉTODO: Estudo analítico de dois casos e revisão sobre o tema no banco de dados da Pubmed/ MedLine e Bireme utilizando as palavras-chave inibidores da fosfodiesterase e surdez súbita e seus correlatos na língua inglesa. RESULTADOS: Os pacientes analisados são jovens, sem comorbidades, em uso de inibidores da fosfodiesterase do tipo 5 e após terapia combinada para o tratamento da surdez súbita, apenas um deles obteve melhora auditiva. Nove estudos científicos foram encontrados. Estudos pré-clínicos e clínicos, transversais e prospectivos foram revisados. CONCLUSÃO: O aumento da ocorrência na prática clínica e relatos científicos na literatura sugerem que o uso de inibidores da fosfodiesterase do tipo 5 seja encarado como fator de risco para surdez súbita. Novos estudos com amostras maiores e grupo controle são necessários para investigar esta associação. .

Phosphodiesterase type 5 Inhibitors, such as sildenafil, vardenafil and tadalafil have been increasingly used today and some of the users have developed sudden sensorineural hearing loss. OBJECTIVE: To present two patients with sudden deafness developed after an occasional use of the drug and review studies on the use of phosphodiesterase type 5 inhibitors and sudden hearing loss. METHOD: Analytical study of two cases and review of the subject matter in the Pubmed/Medline and Bireme databases using the keywords: phosphodiesterase type 5 inhibitors and sudden deafness and its correlates in the English language. RESULTS: The patients analyzed are young without additional disorders, using phosphodiesterase type 5 inhibitors, and after combination treatment for sudden hearing loss only one had hearing improvement. We found nine scientific studies and reviewed preclinical studies, clinical trials, prospective and cross-sectional investigations. CONCLUSION: Increased occurrence in clinical practice and scientific reports in the literature suggest that the phosphodiesterase type 5 inhibitors are considered a risk factor for sudden deafness. Further studies with larger samples and control groups are needed for better assessing this association. .

Assessing the growth and recovery of Salmonella Enteritidis SE86 after sodium dichloroisocyanurate exposure

The objective of the present study was to assess the growth and the recovery of Salmonella (S.) Enteritidis SE86 in different diluents, culture media and using different plating methods after the exposure to 200 mg/kg sodium dichloroisocyanurate (NaDCC). Before and after NaDCC exposure, SE86 was cultured at 30 °C and 7 °C in the following diluents: Peptone water (P), Saline solution (SaS), Peptone water+Saline solution (P+SaS), Peptone water+Tween 80+Lecithin+Sodium thiosulfate (P+N) and Saline solution+Tween 80+Lecithin+Sodium thiosulfate (SaS+N). The SaS diluent was chosen because it was able to maintain cells viable without growth and was further used for plating SE86 on non selective medium (Tryptic Soy Agar-TSA) and on selective media (Mannitol Lysine Crystal Violet Brilliant Green Agar-MLCB; Brilliant Green Agar-BGA; Salmonella Shigella Agar-SS and Xylose Lysine Dextrose-XLD). The Thin Agar Layer method (TAL) i.e., selective media overlayed with non selective TSA was also evaluated. Results indicated that SE86 not exposed to NaDCC was able to grow in P, P+N, SaS+N and P+SaS, but not in SaS, that was able to maintain cells viable. SE86 exposed to NaDCC demonstrated similar counts after dilution in SaS and the plating on non selective TSA, selective media MLCB, BGA, SS and XLD and on TAL media. SE86, S. Typhimurium and S. Bredeney, exposed or not exposed to NaDCC, showed no significant differences in counts on TSA, XLD and XLD overlayed with TSA, suggesting that all those media may be used to quantify NaDCC-exposed Salmonella by plating method.

Avaliação in situ da genotoxicidade de triazinas utilizando o bioensaio Trad-SHM de Tradescantia clone 4430 / In situ genotoxity evaluation of triazines using Tradescantia clone 4430 Trad-SHM bioassay

O bioensaio da mutação do pelo estaminal de Tradescantia clone 4430 (Trad-SHM) foi utilizado para avaliar a genotoxicidade de um herbicida composto por triazinas (atrazina e simazina) após exposição in situ. Trinta vasos da planta foram expostos durante a aplicação do herbicida (grupo teste) mantendo-se um grupo controle em casa de vegetação. A genotoxicidade foi expressa em termos de eventos mutantes pink (EMP) e a análise dos dados foi realizada por meio do teste t de Student em oito dias de avaliação (C8D = controle 8 dias; T8D = teste 8 dias) e no dia de pico (CPD = controle dia de pico; TPD = teste dia de pico). A exposição ao herbicida causou um número significativamente maior de EMP no grupo teste (T8D = 2,27; TPD = 4,69) do que no controle (C8D = 0,71; CPD = 0,62), demonstrando a existência de risco genotóxico associado ao uso das triazinas, sendo o bioensaio Trad-SHM uma eficiente ferramenta para avaliar o poten­cial genotóxico destes contaminantes ambientais causadores de efeitos adversos à saúde humana.

Tradescantia 4430 clone stamen hair mutation (Trad-SHM) bioassay was used to evaluate the genotoxicity of a herbicide composed of triazines (atrazine and simazine) after in situ exposure. Thirty plant pots were exposed during the herbicide application (test group) and a control group was maintained in a greenhouse (control group). Genotoxicity was expressed in terms of pink mutation events (EMPs) and the data analysis was performed by Student's t test comparing the control and contaminated group after eight-days (C8D = 8-day control; T8D = 8-day test) and peak day (CPD = peak day control; TPD = peak day test). Exposure to the herbicide caused a significantly higher number of EMPs in the test group (T8D = 2.27; TPD = 4.69) than in the control group (C8D = 0.71; CPD = 0.62). This demonstrates that the Trad-SHM bioassay is sensitive and efficient and can be used as tool to assess the genotoxic potential of environmental contaminants like triazines associated with adverse effects on human health.

Residuos de plaguicidas en aguas para consumo humano en una comunidad agrícola del estado Mérida, Venezuela / Pesticide residues in drinking water of an agricultural community in the state of Mérida, Venezuela

El objetivo del presente trabajo fue determinar la presencia de plaguicidas en agua potable, provenientes de seis acueductos en una región de intensa actividad agrícola del Estado Mérida, Venezuela. El estudio fue realizado durante cuatro semanas continuas, entre mayo y junio de 2008. Los residuos de plaguicidas fueron analizados mediante extracción en fase sólida y HPLC con detector de arreglo de diodos. El método SPE-HPLC-DAD cumplió con los criterios de validación analítica: linealidad (R²: 0,9840-0,9999), precisión (coeficiente de variabilidad inter-día 1,47-6,25%), exactitud (desviación estándar relativa 0,9-9,20%) y sensibilidad (límite de detección ≤ 0,012 µg/L; límite de cuantificación ≤ 0,030 µg/L, excepto mancozeb con 0,400 µg/L). Siete de los trece plaguicidas seleccionados tienen un porcentaje de recuperación entre 100% y 70%, el resto, entre 61% y 37%. En 72 muestras analizadas, se detectaron diez plaguicidas de los grupos químicos: organofosforados, carbamatos, triazinas y derivados de urea. Los plaguicidas con mayor frecuencia de detección fueron: carbofuran y atrazina (39%), malation (25%), dimetoato y metribuzin (19%). Los plaguicidas que se encontraron en niveles más altos fueron: diazinon (26,31 µg/L), metamidofos (10,99 µg/L), malation (2,03 µg/L) y mancozeb (1,27 µg/L). Los niveles de plaguicidas no superaron los valores máximos permitidos por la Legislación Venezolana, sin embargo, fueron superiores al nivel máximo permitido por la Unión Europea y EPA-USA. Este estudio demuestra la urgente necesidad de hacer un monitoreo sistemático de la calidad del agua para consumo humano en las regiones de alta productividad agrícola.

The aim of this study was to determine the presence of pesticides in drinking water from six aqueducts in a region of intense agricultural activity in the state of Merida, Venezuela. The study was conducted for four continuous weeks, between May and June 2008. Pesticide residues were analyzed by solid phase extraction (SPE) and liquid chromatography (HPLC) with diode array detector (DAD). The method SPE-HPLC-DAD met the criteria of analytical validation, with good linearity (R²: 0.9840 to 0.9999), precision (coefficient of inter-day variability from 1.47 to 6.25%), accuracy (relative standard deviation 0.9 to 9.20%) and sensitivity (LOD ≤ 0.012 µg/L; LOQ ≤ 0.030 µg/L, except mancozeb with 0.400 µg/L). Seven of the thirteen selected pesticides have a recovery rate between 100% and 70%, the rest between 61% and 37%. Ten pesticides of the following chemical groups, were detected in 72 samples analyzed: organophosphates, carbamates, triazines and urea derivatives. The pesticides with the highest frequency of detection were: carbofuran and atrazine (39%), malathion (25%), dimethoate and metribuzin (19%). The pesticides found at high levels were diazinon (26.31 µg/L), methamidophos (10.99 µg/L), malathion (2.03 µg/L) and mancozeb (1.27 µg/L). Pesticide levels did not exceed the maximum allowed by Venezuelan law, however, according to international standards (EU and EPA-USA) values were above the maximum permissible levels. This study demonstrates the urgent need for systematic monitoring of the quality of water for human consumption in regions of high agricultural productivity.

Reacciones cutáneas adversas a anticonvulsivantes y estabilizadores del ánimo / Adverse cutaneous reactions to anticonvulsants and mood stabilizers

Anticonvulsivantes y estabilizadores del ánimo principalmente el ácido valproico, lamotrigina y carbamazepina, poseen una alta incidencia de reacciones adversas a medicamentos (RAM) severas, como eritema multiforme, Síndrome Stevens- Johnson y necrolisis epidérmica tóxica, asociadas. Existen signos de alarma para su sospecha diagnóstica precoz, que permiten indicar la temprana suspensión del fármaco sospechoso e iniciar la terapia de soporte únicas medidas que han demostrado una clara disminución en la mortalidad. La inmunoglobulina G intravenosa se recomienda por su seguridad, sin embargo, su rol en disminuir la mortalidad es contradictorio. Los corticoides no han demostrado cambios en la mortalidad comparados con la terapia de soporte exclusiva. Se ha intentado mantener el tratamiento con lamotrigina, por sus cualidades terapéuticas, pese a la aparición de RAM cutáneas. De hecho, en estudios recientes en pacientes que han desarrollado RAM leves a este producto se ha demostrado un éxito de reexposición de 85 por ciento-87 por ciento mediante una lenta titulación de la dosis.

Anticonvulsants and mood stabilizers mainly valproic acid, lamotrigine and carbamazepine are medications that have a high incidence of severe adverse drug reactions (ADRs), such erythema multiforme, Stevens- Johnson syndrome and toxic epidermal necrolysis. Early diagnosis based in systemic and cutaneous alarm signs have been described, allowing premature discontinuation of suspected drugs and start supportive therapy; these are the only measures that have that have shown clear reduction in mortality. The use of intravenous immunoglobulin G is recommended for their safety, but studies regarding their role in reducing mortality are conflicting. Corticosteroids have not proved changes in mortality compared with exclusive supportive care. Due to therapeutic quality Lamotrigine is used despite the incidence of ADRs. In fact in recent studies patients with mild ADRs to this drug have shown between 85 percent-87 percent of success, when patients are re-exposed through a slow increasing in dosage.

Síndrome de DRESS: eritema cutáneo, fiebre y hepatitis asociado a lamotrigina: reporte de dos casos y revisión de la literatura / DRESS syndrome: skin rash, fever and acute hepatitis associated to lamotrigine: report of two cases and review of the literature

DRESS syndrome is an infrequent adverse drug reaction but in some cases may be life-threatening. It is characterized by cutaneous rash, systemic symptoms and eosinophilia. It is usually caused by aromatic anticonvulsants, sulfonamides and some antiviral drugs, among others. In this article we present two cases of drug induced hypersensitivity syndrome with rash, systemic symptoms (DRESS) associated to lamotrigine therapy with hepatic involvement and a review of the literature. The first case is a 78 year-old woman, presenting with myalgia, fever, abdominal pain and skin rash on her face and extremities. Labora¬tory tests revealed alteration of hepatic profile with hepatocellular pattern. After ruling out other causes, she recognized recent use of lamotrigine. The drug was withdrawn and she had a favourable evolution. The second case is a 30 year-old woman being treated for depression who presented with rash, adenopathies, fever and alteration of hepatic profile twenty four days after starting lamotrigine. Infectious causes were ruled out and she had a good response to corticosteroid treatment.

El síndrome de DRESS es una reacción adversa a medicamentos, poco frecuente pero potencialmente letal. Se caracteriza por eritema cutáneo, síntomas sistémicos y eosinofilia. Suele ser producido por los anticonvulsivantes aromáticos, sulfonamidas y algunos fármacos antivirales, entre otros. En este artículo presentamos dos casos de DRESS secundario a lamotrigina con compromiso hepático y revisión de la literatura. El primero de ellos, una mujer de 78 años, consulta por mialgias, fiebre, dolor abdominal y eritema maculopapular en cara y extremidades. Los exámenes de laboratorio revelaron alteración de pruebas de función hepática con patrón hepatocelular. Luego de descartar otras causas, la paciente reconoció uso reciente de lamotrigina. Se suspendió la droga y evolucionó favorablemente. El segundo caso es una mujer de 30 años en tratamiento por trastorno depresivo quien, veinticuatro días post-inicio de lamotrigina, comienza con eritema, adenopatías, fiebre y alteración de pruebas de función hepática, excluyéndose etiologías infecciosas; se inicia tratamiento corticoesteroidal con buena respuesta.

Síndrome de hipersensibilidad a anticonvulsivantes (síndrome de DRESS): comunicación de 4 casos / Anticonvulsant hypersensitivity syndrome (DRESS syndrome): report of 4 cases

El síndrome de hipersensibilidad a anticonvulsivante es una reacción frecuente y potencialmente fatal, que se caracteriza por fiebre, erupción cutánea y compromiso de órganos internos. Difenilhidantína, fenobarbital y carbamazepina son los anticonvulsivantes aromáticos que más frecuentemente lo producen. Comunicamos 4 pacientes adultos, 2 masculinos y 2 femeninos de entre 20 y 42 años que presentaron hallazgos clínicos, bioquímicos e histológicos compatibles con un síndrome de hipersensibilidad a drogas secundario a anticonvulsivantes que se inició luego de 4 a 8 semanas del inicio del fármaco. Las drogas causantes fueron difenilhidantoína, carbamazepina y la asociación de ácido valproico y lamotrigina.