Two cases of neural tube defects with dolutegravir use at conception in south Brazil

ABSTRACT Dolutegravir (DTG) is amongst the most prescribed antiretrovirals worldwide and is recommended as first line regimen in most HIV treatment guidelines. Its use, although infrequently, had been associated to an increased chance of neural tube defects (NTD) in Botswana, Africa. Herein we describe two cases of NTD in women who conceived while taking DTG as part of their antiretroviral treatment in the city of Porto Alegre, Brazil.

Which antiretroviral regimen is associated with higher adherence in Brazil? A comparison of single, multi, and dolutegravir-based regimens / Qual esquema antirretroviral está associado à maior adesão no Brasil? Uma comparação dos esquemas de comprimido único, múltiplos comprimidos e com dolutegravir / ¿Qué tratamiento antirretroviral está asociado con adherencia más alta en Brasil? Una comparación de tratamientos únicos, múltiples y basados en el dolutegravir

Abstract: We evaluated adherence to highly active antiretroviral therapy (HAART) and its associated factors according to the type of regimen in patients initiating treatment in Belo Horizonte, Minas Gerais State, Brazil. We measured adherence using the eight items Morisky Therapeutic Adhesion Scale (MMAS-8) and compared the use of "backbone" tenofovir/lamivudine plus efavirenz one tablet once-daily (STR) or dolutegravir in multi-tablet once-daily (MTR-DTG), or other multi-tablet regimens (MTR-other). We conducted a multivariate logistic regression analysis to address factors associated with adherence. A total of 393 patients were included, 254 used STR, 106 MTR-DTG, and 33 MTR-other. The overall adhesion rate was 44.8% (95%CI: 39.4; 50.1), 50% for MTR-DTG, 43.3% for STR and 39.4% for MTR-other. Multivariate analysis showed a higher chance of adherence among patients using MTR-DTG, those who received and understood counseling about their treatment and with a higher quality of life. Prior use of illicit drugs in the lifetime was associated with poorer adherence. Overall adherence was low, highlighting the need for strategies focusing on counseling about medicines and substance use. Pill burden was not an issue for patients using MTR-DTG once-daily, who achieved better results.

Resumo: Avaliamos a adesão à terapia antirretroviral (TARV) e fatores associados de acordo com o tipo de esquema em pacientes no início do tratamento em Belo Horizonte, Minas Gerais, Brasil. Mensuramos a adesão com a Escala de Adesão Terapêutica de Morisky, de oito itens (MMAS-8), e comparamos o uso de tenofovir/lamivudina com efavirenz, um comprimido uma vez ao dia (STR), ou dolutegravir em múltiplos comprimidos uma vez ao dia (MTR-DTG), com outros esquemas com múltiplos comprimidos ao dia (MTR-outros). Conduzimos uma análise de regressão logística multivariada para avaliar os fatores associados à adesão. Foram incluídos 393 pacientes: 254 em uso de STR, 106 MTR-DTG e 33 MTR-outros. A taxa global de adesão foi 44,8% (IC95%: 39,4; 50,1), sendo 50% para MTR-DTG, 43,3% para STR e 39,4% para MTR-outros. A análise multivariada mostrou chances maiores de adesão em pacientes em uso de MTR-DTG, pacientes que haviam recebido e compreendido o aconselhamento sobre o tratamento e pacientes com melhor qualidade de vida. Uso anterior de drogas ilícitas em qualquer período da vida está associada à pior adesão. A adesão global foi baixa, enfatizando a necessidade de estratégias focadas no aconselhamento sobre medicamentos e uso de drogas. A quantidade de comprimidos não foi um problema para pacientes em uso de MTR-DTG uma vez ao dia, os quais alcançaram melhores taxas de adesão.

Resumen: Evaluamos la adherencia a la terapia antirretroviral altamente activa (TARAA) y sus factores asociados, según el tipo de tratamiento en pacientes que comenzaron su tratamiento en Belo Horizonte, Minas Gerais, Brasil. La adherencia se mensuró por la Escala de Adhesión Terapéutica de Morisky, de ocho ítems (MMAS-8), y se comparó el uso del "eje" tenofovir/lamivudina, además de un comprimido de efavirenz una vez al día (STR) o dolutegravir con varios comprimidos una vez al día (MTR-DTG), u otros tratamientos con múltiples comprimidos (MTR-otros). Se realizó un análisis multivariado de regresión logística para evaluar los factores asociados a la adherencia. Se incluyeron un total de 393 pacientes, 254 usaron STR, 106 MTR-DTG, y 33 MTR-Otros. La tasa de adherencia general fue de un 44,8% (95%CI: 39,4; 50,1), 50% en el MTR-DTG, 43,3% en el STR y 39,4% en el MTR-otros. El análisis multivariado mostró una probabilidad más alta de adherencia entre pacientes usando MTR-DTG, quienes recibieron y comprendieron las orientaciones acerca de sus tratamientos y los que disfrutaban de una calidad mejor de vida. El consumo previo de drogas ilícitas a lo largo de la vida estuvo asociado con una adherencia más escasa. La adherencia general fue baja y resalta la necesidad de estrategias que se enfoquen en brindar orientación sobre el uso de la medicación y de sustancias. El número de comprimidos no fue un problema para los pacientes que tomaban MTR-DTG una vez al día, que obtuvieron mejores resultados.

Detection of carboxylesterase and esterase activity in culturable gut bacterial flora isolated from diamondback moth, Plutella xylostella (Linnaeus), from India and its possible role in indoxacarb degradation

Abstract Diamondback moth (DBM), Plutella xylostella (Linnaeus), is a notorious pest of brassica crops worldwide and is resistant to all groups of insecticides. The insect system harbors diverse groups of microbiota, which in turn helps in enzymatic degradation of xenobiotic-like insecticides. The present study aimed to determine the diversity of gut microflora in DBM, quantify esterase activity and elucidate their possible role in degradation of indoxacarb. We screened 11 geographic populations of DBM in India and analyzed them for bacterial diversity. The culturable gut bacterial flora underwent molecular characterization with 16S rRNA. We obtained 25 bacterial isolates from larvae (n = 13) and adults (n = 12) of DBM. In larval gut isolates, gammaproteobacteria was the most abundant (76%), followed by bacilli (15.4%). Molecular characterization placed adult gut bacterial strains into three major classes based on abundance: gammaproteobacteria (66%), bacilli (16.7%) and flavobacteria (16.7%). Esterase activity from 19 gut bacterial isolates ranged from 0.072 to 2.32 µmol/min/mg protein. Esterase bands were observed in 15 bacterial strains and the banding pattern differed in Bacillus cereus – KC985225 and Pantoea agglomerans – KC985229. The bands were characterized as carboxylesterase with profenofos used as an inhibitor. Minimal media study showed that B. cereus degraded indoxacarb up to 20%, so it could use indoxacarb for metabolism and growth. Furthermore, esterase activity was greater with minimal media than control media: 1.87 versus 0.26 µmol/min/mg protein. Apart from the insect esterases, bacterial carboxylesterase may aid in the degradation of insecticides in DBM.

Dormancy models for Mycobacterium tuberculosis: A minireview

Dormancy models for Mycobacterium tuberculosis play important roles in understanding various aspects of tuberculosis pathogenesis and in the testing of novel therapeutic regimens. By simulating the latent tuberculosis infection, in which the bacteria exist in a non-replicative state, the models demonstrate reduced susceptibility to antimycobacterial agents. This minireview outlines the models available for simulating latent tuberculosis both in vitro and in several animal species. Additionally, this minireview discusses the advantages and disadvantages of these models for investigating the bacterial subpopulations and susceptibilities to sterilization by various antituberculosis drugs.

Neonatal screening program for hemoglobinopathies in the city of São Carlos, state of São Paulo, Brazil: analysis of a series of cases / Triagem neonatal de hemoglobinopatias no município de São Carlos, São Paulo, Brasil: análise de uma série de casos

OBJECTIVE: To analyze the neonatal screening program for hemoglobinopathies in São Carlos, Southeast Brazil, by investigating a series of cases in which the screening test was abnormal. More specifically, it was aimed to know the information regarding the neonatal screening received by mothers at the hospital and at primary health care, in addition to information related to genetic counseling. METHODS: A descriptive study that enrolled 119 mothers, accounting for 73% of all children born between 2010 and 2011 with abnormal results of neonatal screening for hemoglobinopathies. The mothers completed a questionnaire that assessed the information received at hospital and primary health care, and issues related to genetic counseling. Descriptive statistics was performed. RESULTS: Of the 119 participating mothers, 69 (58%) had children with sickle cell trait, 22 (18.5%) with hemoglobin C trait, 18 (15.1%) with alpha thalassemia trait and, in 10 cases (8.4%), the result was inconclusive. At the hospital, 118 mothers (99.2%) received information about where to go to collect the test and 115 (96.6%) were informed about the correct time to collect the test. Only 4 mothers (3.4%) were informed about which diseases are investigated and the risks of not performing the screening. Seventeen mothers (14.3%) recognized the difference between trait and disease, and 42 (35.3%) considered that a positive screening test could have implications for future pregnancies. In 70 cases (58.8%), the child's physician was not informed about the screening test results. CONCLUSIONS: The neonatal screening program needs further improvement. In both scenarios investigated, health professionals demonstrated a lack of training in providing information to mothers and families. .

OBJETIVO: Fazer uma análise do programa de triagem neonatal de hemoglobinopatias no município de São Carlos, São Paulo, Brasil, por meio da investigação de série de casos cujo resultado do teste de rastreio foi alterado. Objetivou-se conhecer as informações a respeito da triagem neonatal recebidas pelas mães na maternidade e na atenção primária à saúde, além das informações relacionadas à orientação genética. MÉTODOS: Estudo descritivo, no qual participaram 119 mães cujos filhos apresentaram teste de triagem de hemoglobinopatia alterado, o que correspondeu a 73% das crianças nascidas entre 2010 e 2011 com resultado de triagem neonatal para hemoglobinopatia anormal. As mães responderam um questionário que avaliou informações recebidas na maternidade e na atenção primária à saúde, além de aspectos relacionados à orientação genética. Foi feita estatística descritiva dos dados. RESULTADOS: Das 119 mães participantes, 69 (58%) tinham filhos com traço falciforme, 22 (18,5%) traço C, 18 (15,1%) traço alfatalassêmico e 10 (8,4%) resultado inconclusivo. Na maternidade, 118 mães (99,2%) receberam informação sobre onde ir e 115 (96,6%) foram orientadas sobre o momento correto para coleta do teste. Somente quatro mães (3,4%) foram informadas sobre quais doenças seriam investigadas e os riscos de não fazer o rastreio. Das 119 mães participantes, 17 (14,3%) reconheceram a diferença entre traço e doença e 42 (35,3%) consideraram que um teste alterado poderia ter implicações para futuras gestações. Em 70 casos (58,8%), o médico da criança não foi informado sobre o resultado da triagem. CONCLUSÕES: O programa de triagem neonatal necessita de aperfeiçoamento. Nos dois cenários investigados, os profissionais de saúde carecem de treinamento para orientar mães e famílias. .

Early responses of the STAT3 pathway to platinum drugs are associated with cisplatin resistance in epithelial ovarian cancer

Cisplatin resistance remains one of the major obstacles when treating epithelial ovarian cancer. Because oxaliplatin and nedaplatin are effective against cisplatin-resistant ovarian cancer in clinical trials and signal transducer and activator of transcription 3 (STAT3) is associated with cisplatin resistance, we investigated whether overcoming cisplatin resistance by oxaliplatin and nedaplatin was associated with the STAT3 pathway in ovarian cancer. Alamar blue, clonogenic, and wound healing assays, and Western blot analysis were used to compare the effects of platinum drugs in SKOV-3 cells. At an equitoxic dose, oxaliplatin and nedaplatin exhibited similar inhibitory effects on colony-forming ability and greater inhibition on cell motility than cisplatin in ovarian cancer. Early in the time course of drug administration, cisplatin increased the expression of pSTAT3 (Tyr705), STAT3α, VEGF, survivin, and Bcl-XL, while oxaliplatin and nedaplatin exhibited the opposite effects, and upregulated pSTAT3 (Ser727) and STAT3β. The STAT3 pathway responded early to platinum drugs associated with cisplatin resistance in epithelial ovarian cancer and provided a rationale for new therapeutic strategies to reverse cisplatin resistance.

Comparative evaluation of the microplate nitrate reductase assay and the rezasurin microtitre assay for the rapid detection of multidrug resistant Mycobacterium tuberculosis clinical isolates

The microplate nitrate reductase assay (MNRA) and the rezasurin microtitre assay (REMA) were used for the susceptibility testing of 73 clinical isolates and the results were compared with those that were obtained using the Bactec 460 TB and Bactec MGIT 960 systems. The REMA and the MNRA were performed in 96-well plates. For the REMA, the concentrations of isoniazid (INH) and rifampicin (RIF) ranged from 1.0-0.01 µg/mL and 2.0-0.03 µg/mL, respectively. For the MNRA, the INH concentration was between 1.0-0.03 µg/mL and the RIF concentration was between 2.0-0.06 µg/mL. For the MNRA, the sensitivity, specificity, positive predictive value, negative predictive value and INH/RIF agreement were 100/95.6, 97.6/100, 96.8/100, 100/98 and 98.6/98.6, respectively, and for the REMA, they were 100/91.3, 90.4/100, 88.5/100, 100/96.1 and 94.5/97.2, respectively. Our data suggest that these two rapid, low-cost methods may be inexpensive, alternative assays for the rapid detection of multidrug resistant tuberculosis in low-income countries.

Validation of a modified fluorimetric assay for the screening of trichomonacidal drugs

A fluorimetric microassay that uses a redox dye to determine the viability of the flagellate Trichomonas vaginalis has been optimised to provide a more sensitive method to evaluate potential trichomonacidal compounds. Resazurin has been used in recent years to test drugs against different parasites, including trichomonadid protozoa; however, the reproducibility of these resazurin-based methods in our laboratory has been limited because the flagellate culture medium spontaneously reduces the resazurin. The objective of this work was to refine the fluorimetric microassay method previously developed by other research groups to reduce the fluorescence background generated by the media and increase the sensitivity of the screening assay. The experimental conditions, time of incubation, resazurin concentration and media used in the microtitre plates were adjusted. Different drug sensitivity studies against T. vaginalis were developed using the 5-nitroimidazole reference drugs, new 5-nitroindazolinones and 5-nitroindazole synthetic derivatives. Haemocytometer count results were compared with the resazurin assay using a 10% solution of 3 mM resazurin dissolved in phosphate buffered saline with glucose (1 mg/mL). The fluorimetric assay and the haemocytometer counts resulted in similar percentages of trichomonacidal activity in all the experiments, demonstrating that the fluorimetric microtitre assay has the necessary accuracy for high-throughput screening of new drugs against T. vaginalis.

Aptitud biológica de poblaciones de Bemisia tabaci (Gennadius) Biotipo B (Hemiptera: Aleyrodidae) con diferente susceptibilidad al insecticida thiametoxam / Fitness of Bemisia tabaci (Gennadius) B Biotype (Hemiptera: Aleyrodidae) populations with different levels of susceptibility to the thiametoxam insecticide

In two field-collected populations of de Bemisia tabaci (Gennadius) B biotype previously selected with the neonicotinoid insecticide thiamethoxam (NEO-R, NEO-N), and a population susceptible to insecticides (SUSC), the level of response to the insecticide thiametoxam, as well as the life and fertility tables were determined. At LC95, the NEO-R population showed a resistance ratio (RR95) value of 8.8-fold, an intrinsic rate of increase (r m) of 0.72. The fitness of the NEO-R and NEO-N populations in relation to the SUSC was 1.5 and 2.0, respectively. The RR95 value for NEO-N was 1.9-fold; it's r m value was 0.082, while in the SUSC population was 0.041. The developmental time of egg and adult were longer in NEO-R population, while the nymph and pupa lasted longer in the NEO-N and SUSC populations. The developmental time was different in the three NEO-R, NEO-N, and SUSC populations with 19.7 d (315.84 degree days or dd), 15.7 d (250.4 dd) and 18.5 d (296.6 d), respectively. The populations previously selected with thiamethoxam did not reproduce faster than their susceptible counterpart.

A simple method to measure cell viability in proliferation and cytotoxicity assays

Resazurin dye has been broadly used as indicator of cell viability in several types of assays for evaluation of the biocompatibility of medical and dental materials. Mitochondrial enzymes, as carriers of diaphorase activities, are probably responsible for the transference of electrons from NADPH + H+ to resazurin, which is reduced to resorufin. The level of reduction can be quantified by spectrophotometers since resazurin exhibits an absorption peak at 600 çm and resorufin at 570 çm wavelengths. However, the requirement of a spectrophotometer and specific filters for the quantification could be a barrier to many laboratories. Digital cameras containing red, green and blue filters, which allow the capture of red (600 to 700 çm) and green (500 to 600 çm) light wavelengths in ranges bordering on resazurin and resorufin absorption bands, could be used as an alternative method for the assessment of resazurin and resorufin concentrations. Thus, our aim was to develop a simple, cheap and precise method based on a digital CCD camera to measure the reduction of resazurin. We compared the capability of the CCD-based method to distinguish different concentrations of L929 and normal Human buccal fibroblast cell lines with that of a conventional microplate reader. The correlation was analyzed through the Pearson coefficient. The results showed a strong association between the measurements of the method developed here and those made with the microplate reader (r² = 0.996; p < 0.01) and with the cellular concentrations (r² = 0.965; p < 0.01). We concluded that the developed Colorimetric Quantification System based on CCD Images allowed rapid assessment of the cultured cell concentrations with simple equipment at a reduced cost.

Cytogenetic analysis in the spermatogenesis of Triatoma melanosoma (Reduviidae; Heteroptera)

Triatomines are of great concern in public health because they are vectors of Chagas’ disease. This study presents an analysis of the species Triatoma melanosoma. The cytogenetic characteristics of triatomines include holocentric chromosomes, post-reductional meiosis in the sex chromosomes and nucleolar fragmentation in the meiotic cycle. The methodology utilized consisted of the techniques of lacto-acetic orcein staining and silver ion impregnation. The organs analyzed were adult testicles. The results enabled to classify the chromosomes by number and size, being three large, eight medium and one small heterochromosome. The three largest chromosomes and the heterochromosomes showed heteropyknotic chromatin in meiosis. The heterochromosomes in 8.05% of the cells in metaphase I behaved as pseudobivalents, contrasting with 91.95% of the cells with individualized sex chromosomes, confirming the achiasmatic nature of these chromosomes. However, the pseudobivalents occurred prominently in metaphase II (78.38%), this fact probably is related to the post-reductional nature of the sex chromosomes. The nucleolus in T. melanosoma persisted until the diplotene phase after which it began to fragment. Nucleolar corpuscles were observed in metaphases I and II and during anaphases I and II, these characteristics being related to the phenomenon of nucleolar persistence. In the initial spermatids, peripheral silver ion impregnation occurred, which could be analogous to the pre-nucleolar corpuscles observed after fragmentation. Thus, this study extends our knowledge of the characteristics of triatomines, in particular, heteropyknotic degree, kinetic activity, formation of sex chromosome achiasmatic pseudobivalency, confirmation of the fragmentation phenomenon, and post-meiotic nucleolar reactivation.

The effects of drugs, ions, and poly-l-lysine on the excretory system of Schistosoma mansoni

We have been able to label the excretory system of cercariae and all forms of schistosomula, immature and adult worms with the highly fluorescent dye resorufin. We have shown that the accumulation of the resorufin into the excretory tubules and collecting ducts of the male adult worm depends on the presence of extracellular calcium and phosphate ions. In the adult male worms, praziquantel (PZQ) prevents this accumulation in RPMI medium and disperses resorufin from tubules which have been prelabelled. Female worms and all other developmental stages are much less affected either by the presence of calcium and phosphate ions, or the disruption caused by PZQ. The male can inhibit the excretory system in paired female. Fluorescent PZQ localises in the posterior gut (intestine) region of the male adult worm, but not in the excretory system, except for the anionic carboxy fluorescein derivative of PZQ, which may be excreted by this route. All stages of the parasite can recover from damage by PZQ treatment in vitro. The excretory system is highly sensitive to damage to the surface membrane and may be involved in vesicle movement and damage repair processes. In vivo the adult parasite does not recover from PZQ treatment, but what is inhibiting recovery is unknown, but likely to be related to immune effector molecules.

Urinary NO3 excretion and renal failure in indinavir-treated patients

Treatment with indinavir (IDV), a protease inhibitor, is frequently associated with renal abnormalities. We determined the incidence of renal failure (creatinine clearance <80 mL min-1 1.73 (m²)-1) in HIV patients treated with highly active antiretroviral therapy, including IDV, and investigated the possible mechanisms and risk factors of IDV nephrotoxicity. Thirty-six patients receiving IDV were followed for 3 years. All were assessed for age, body weight, duration of infection, duration of IDV treatment, sulfur-derivative use, total cholesterol, triglycerides, magnesium, sodium, potassium, creatinine, and urinalysis. We also determined renal function in terms of creatinine clearance, urine osmolality and fractional excretion of sodium, potassium, and water. Urinary nitrate (NO3) excretion was measured in 18 IDV-treated patients and compared with that of 8 patients treated with efavirenz, a drug without renal side effects. Sterile leukocyturia occurred in 80.5 percent of the IDV-treated patients. Creatinine clearance <80 mL min-1 1.73 (m²)-1 was observed in 22 patients (61 percent) and was associated with low body weight and the use of sulfur-derivatives. These patients also had lower osmolality, lower urine volume and a higher fractional excretion of water compared to the normal renal function group. Urinary NO3 excretion was significantly lower in IDV-treated patients (809 ± 181 æM NO3-/mg creatinine) than in efavirenz-treated patients (2247 ± 648 æM NO3-/mg creatinine, P < 0.01). The lower NO3 excretion suggests that IDV decreases nitric oxide production.

Resíduos de tiametoxam, aldicarbe e de seus metabólitos em folhas de cafeeiro e efeito no controle de Leucoptera coffeella (Guérin-Mèneville) (Lepidoptera: Lyonetiidae) / Residues of thiamethoxam, aldicarb and its metabolites in coffee leaves and effect on the Control of Leucoptera coffeella (Guérin-Mèneville) (Lepidoptera: Lyonetiidae)

O bicho-mineiro Leucoptera coffeella (Guérin-Mèneville), uma das pragas mais importantes da cafeicultura brasileira, é controlado principalmente com inseticidas. O objetivo deste trabalho foi estudar os resíduos e a translocação do inseticida tiametoxam em folhas de cafeeiros, bem como avaliar seu efeito no controle do bicho-mineiro, comparando-o com o aldicarbe, utilizado como padrão. Para isto, foi instalado um experimento no município de Garça, SP, no período de dezembro/2001 a agosto/2002. Os tratamentos utilizados foram: aldicarbe 150 G, nas doses de 2,25 e 4,50 g i.a./cova, tiametoxam 10 GR, nas doses de 0,15 e 0,30 g i.a./cova e testemunha (sem aplicação). Amostras de ramos foram colhidas em pré-contagem e aos 30, 60, 90, 120, 150, 180, 210 e 240 dias após a aplicação, em três alturas dos cafeeiros (terços inferior, médio e superior), avaliando-se a porcentagem de folhas minadas. As determinações de aldicarbe e seus metabólitos ativos, aldicarbe sulfoxido e sulfona, e os de tiametoxam foram feitas por cromatografia em fase gasosa usando-se detector de nitrogênio-fósforo e de espectrometria de massas, respectivamente. Os resultados indicaram translocação uniforme de ambos inseticidas nos três terços das plantas de café, quando aplicados no solo. Foi constatada também, a maior persistência do tiametoxam, cujos resíduos foram encontrados até oito meses após a aplicação, enquanto os metabólitos sulfóxido e sulfona foram encontrados entre quatro e seis meses após a aplicação. Foi observado controle do bicho-mineiro pela aplicação de ambos inseticidas.

Thyroid hormones and the pathophysiology of brain ischemia

Foi investigado o papel do hormônio tiroideano 3,5,3,' -triiodotironina (T3) na patofisiologia da isquemia cerebral. Um grupo de ratos foi submetido à oclusäo de quatro vasos durante 5 min para induzir isquemia cerebral anterior sob normotermia (37,0 ñ 0,5 -C). Cada animal (n = 5) recebeu uma microinjeçäo de T3 em um dos hipocampos dorsais (HPC) e outra, de igual volume, de veículo (0,5 µl de tampäo de fosfato 0,1 M, pH 7,4) no HPC contralateral 5min antes da isquemia cerebral anterior. Um segundo grupo (sham-operado, n=5) recebeu as mesmas microinjeçöes de T3 e de veículo por via intra-hipocampal. Os anaimais foram mortos 72 após os diferentes tratamentos. Nos grupos isquêmicos, os cortes cerebrais coronais corados com violeta de cresila revelaram alteraçöes isquêmicas mais entensas nos hipocampos injetados com T3 quando comparados aos contralaterais. Esses achados assimétricos geralmente eram restritos ou mais intensos ao redor do sítio da injeçäo. Nossos achados sugerem que T3 pode ser um medidor importante das alteraçöes neuronais desencadeadas pelo insulto isquêmico e levantaram a possibilidade de um papel terapêutico de antagonistas T3 periféricos na isquemia cerebral

Effects of phenylethylamine on rat locomotor behavior and avoidance learning

1. The effects of ß-phenylethylamine (PEA) alone and in association with caroxazone, a potent inhibitor of monoamine oxidase B (MAO B), on the activity and long-term memory in the wheel-shaped activity monitor and on fixed-interval two-way avoidance acquisition were studied in rats. In a separate study, we determined the effects of PEA and of d-amphetamine on the variable-internal two-way avoidance acquisition. 2. The action of PEA was markedly different from that of aplhetamine in several aspects. The stimulating effects of PEA in the wheel-shaped activity monitor were of a more subtle nature than those of amphetamine and in the variable-interval two-way avoidance acquisition PEA had no effect, while amphetamine improved performance. 3. PEA did not induce an increase in path-choice stereotypy, but caroxazone did. The absence of any caroxazone-session interaction effects on the path interation frequency suggested that there were no long-term memory effects. 4. In the fixed-interval two-way avoidance acquisition experiments, PEA increased the avoidance responses of tats while caroxazone had no effect. The association of the two drugs did not potenciate either