Envenenamento ofídico em crianças: frequência de reações precoces ao antiveneno em pacientes que receberam pré-tratamento com antagonistas H1 e H2 da histamina e hidrocortisona

Foram estudadas 24 crianças, com idade entre 2 a 14 anos, de 1989 a 1993, vítimas de acidentes ofídicos, submetidas a pré-tratamento com antagonistas H1 (dextroclorfeniramina) e H2 (cimetidine ou ranitidina) da histamina e hidrocortisona, com objetivo de avaliar a frequência e o tipo de reações precoces (RP) ao antiveneno (AV). Em nenhum paciente havia antecedente de atopia ou uso prévio de algum tipo de antiveneno ou antitoxina heteróloga. Das 24 crianças 15 receberam AV botrópico (RP em 5), 7 AV crotálico (RP em 5), 1 AV crotálico e AV botrópico-crotálico e 1 AV elapídico (RP). Foram observadas RP graves em 3 crianças, as 3 classificadas como acidente crotálico grave. A análise dos resultados sugere que o pré-tratamento realizado não ofereceu uma proteção segura quanto ao aparecimento de RP.

Effect of histamine H1 and H2 receptor antagonists, microinjected into cerebellar vermis, on emotional memory consolidation in mice

This study investigated the effects of histamine H1 or H2 receptor antagonists on emotional memory consolidation in mice submitted to the elevated plus maze (EPM). The cerebellar vermis of male mice (Swiss albino) was implanted using a cannula guide. Three days after recovery, behavioral tests were performed in the EPM on 2 consecutive days (T1 and T2). Immediately after exposure to the EPM (T1), animals received a microinjection of saline (SAL) or the H1 antagonist chlorpheniramine (CPA; 0.016, 0.052, or 0.16 nmol/0.1 µL) in Experiment 1, and SAL or the H2 antagonist ranitidine (RA; 0.57, 2.85, or 5.7 nmol/0.1 µL) in Experiment 2. Twenty-four hours later, mice were reexposed to the EPM (T2) under the same experimental conditions but they did not receive any injection. Data were analyzed using one-way ANOVA and the Duncan test. In Experiment 1, mice microinjected with SAL and with CPA entered the open arms less often (%OAE) and spent less time in the open arms (%OAT) in T2, and there was no difference among groups. The results of Experiment 2 demonstrated that the values of %OAE and %OAT in T2 were lower compared to T1 for the groups that were microinjected with SAL and 2.85 nmol/0.1 µL RA. However, when animals were microinjected with 5.7 nmol/0.1 µL RA, they did not show a reduction in %OAE and %OAT. These results demonstrate that CPA did not affect behavior at the doses used in this study, while 5.7 nmol/0.1 µL RA induced impairment of memory consolidation in the EPM.

Haplotype analysis of vernalization loci in European barley germplasm reveals novel VRN-H1 alleles and a predominant winter VRN-H1/VRN-H2 multi-locus haplotype

In barley, variation in the requirement for vernalization (an extended period of low temperature before flowering can occur) is determined by the VRN-H1, -H2 and -H3 loci. In European cultivated germplasm, most variation in vernalization requirement is accounted for by alleles at VRN-H1 and VRN-H2 only, but the range of allelic variation is largely unexplored. Here we characterise VRN-H1 and VRN-H2 haplotypes in 429 varieties representing a large portion of the acreage sown to barley in Western Europe over the last 60 years. Analysis of genotype, intron I sequencing data and growth habit tests identified three novel VRN-H1 alleles and determined the most frequent VRN-H1 intron I rearrangements. Combined analysis of VRN-H1 and VRN-H2 alleles resulted in the classification of seventeen VRN-H1/VRN-H2 multi-locus haplotypes, three of which account for 79% of varieties. The molecular markers employed here represent powerful diagnostic tools for prediction of growth habit and assessment of varietal purity. These markers will also allow development of germplasm to test the behaviour of individual alleles with the aim of understanding the relationship between allelic variation and adaptation to specific agri-environments.

Reações de hipersensibilidade imediatas após uso intravenoso de soros antivenenos: valor prognóstico dos testes de sensibilidade intradérmicos

Foram admitidos no Hospital das Clínicas da FMRPUSP, durante os anos de 1983 a 1988, 494 pacientes vítimas de acidentes ofídicos e escorpiônicos que receberam soro antiveneno (SAV) e nos quais foi avaliada a freqüência e tipo das manifestações imediatas, bem como o valor prognóstico do teste de sensibilidade. Do total de pacientes vítimas de ofidismo, 82 (25,6%) apresentaram reações imediatas, das quais as mais comuns foram as cutâneas, isoladas (40%) ou associadas com sintomas respiratórios (19%), seguidas de manifestações gastrintestinais (17%). Choque anafilático foi detectado em 10 pacientes (12%). Em relação aos acidentes escorpiônicos, reações imediatas foram observadas em 13 pacientes (7,5%), também com predomínio de lesões cutâneas. Sintomatologia cardiocirculatória foi detectada em apenas 1 paciente. Devido ao baixo valor preditivo positivo (31,8%) e à baixa sensibilidade (54,6%), propomos que o teste de sensibilidade intradérmico seja abolido da rotina de atendimento de urgência aos pacientes vítimas de acidentes por animais peçonhentos. Anti-histamínicos (bloqueadores dos receptores H1 e H2) e corticosteróides devem ser administrados por via parenteral anteriormente à soroterapia, no sentido de prevenir ou minimizar as reações de hipersensibilidade imediatas que podem ocorrer. O soro antiveneno deve ser sempre administrado por via intravenosa, de preferência sem diluição, gota a gota, durante 15 a 30 minutos, sob contínua supervisão da equipe médica.

Resposta cronotrópica ao teste cardiopulmonar após o uso de cimetidina

OBJETIVO: Testar a hipótese, por meio de ensaio clínico randomizado, de que a administração de cimetidina altera a resposta cronotrópica ao exercício. MÉTODOS: Foram selecionados 24 indivíduos saudáveis, com idade entre 20 e 68 anos, não-atletas, os quais concordaram em ser submetidos a testes cardiopulmonares, após uso de placebo e de cimetidina, 400 mg, duas vezes ao dia, durante uma semana. Os testes foram realizados em esteira rolante, com protocolo de rampa com análises diretas dos gases expirados. Foi avaliada freqüência cardíaca máxima atingida, além da freqüência cardíaca de repouso e do limiar anaeróbico. RESULTADOS: Os indivíduos estudados foram igualmente distribuídos por sexo, com idade média (± desvio padrão) de 43 ±11 anos. Os exames com placebo e com cimetidina tiveram igual duração (578±90 seg vs 603±131 seg) e igual VO2 pico (35±8 ml/kg.min vs 35±8 ml/kg.min). A administração de cimetidina não apresentou efeito significativo na freqüência cardíaca de repouso (75±10 vs 74±8 bpm), no pico do esforço (176±12 vs 176±11 bpm) e, da mesma forma, também não houve diferença entre as variações das freqüências cardíacas (pico - repouso), nos dois estudos (101±14 vs 101±13 bpm). CONCLUSÃO: A administração de cimetidina por sete dias não altera a resposta cronotrópica ao exercício.

H1 but not H2 histamine antagonist receptors mediate anxiety-related behaviors and emotional memory deficit in mice subjected to elevated plus-maze testing

This study investigated the role of H1 and H2 receptors in anxiety and the retrieval of emotional memory using a Trial 1/Trial 2 (T1/T2) protocol in an elevated plus-maze (EPM). Tests were performed on 2 consecutive days, designated T1 and T2. Before T1, the mice received intraperitoneal injections of saline (SAL), 20 mg/kg zolantidine (ZOL, an H2receptor antagonist), or 8.0 or 16 mg/kg chlorpheniramine (CPA, an H1 receptor antagonist). After 40 min, they were subjected to the EPM test. In T2 (24 h later), each group was subdivided into two additional groups, and the animals from each group were re-injected with SAL or one of the drugs. In T1, the Student t-test showed no difference between the SAL and ZOL or 8 mg/kg CPA groups with respect to the percentages of open arm entries (%OAE) and open arm time (%OAT). However, administration of CPA at the highest dose of 16 mg/kg decreased %OAE and %OAT, but not locomotor activity, indicating anxiogenic-like behavior. Emotional memory, as revealed by a reduction in open arm exploration between the two trials, was observed in all experimental groups, indicating that ZOL and 8 mg/kg CPA did not affect emotional memory, whereas CPA at the highest dose affected acquisition and consolidation, but not retrieval of memory. Taken together, these results suggest that H1 receptor, but not H2, is implicated in anxiety-like behavior and in emotional memory acquisition and consolidation deficits in mice subjected to EPM testing.

H1 but not H2 histamine antagonist receptors mediate anxiety-related behaviors and emotional memory deficit in mice subjected to elevated plus-maze testing

This study investigated the role of H1 and H2 receptors in anxiety and the retrieval of emotional memory using a Trial 1/Trial 2 (T1/T2) protocol in an elevated plus-maze (EPM). Tests were performed on 2 consecutive days, designated T1 and T2. Before T1, the mice received intraperitoneal injections of saline (SAL), 20 mg/kg zolantidine (ZOL, an H2 receptor antagonist), or 8.0 or 16 mg/kg chlorpheniramine (CPA, an H1 receptor antagonist). After 40 min, they were subjected to the EPM test. In T2 (24 h later), each group was subdivided into two additional groups, and the animals from each group were re-injected with SAL or one of the drugs. In T1, the Student t-test showed no difference between the SAL and ZOL or 8 mg/kg CPA groups with respect to the percentages of open arm entries (%OAE) and open arm time (%OAT). However, administration of CPA at the highest dose of 16 mg/kg decreased %OAE and %OAT, but not locomotor activity, indicating anxiogenic-like behavior. Emotional memory, as revealed by a reduction in open arm exploration between the two trials, was observed in all experimental groups, indicating that ZOL and 8 mg/kg CPA did not affect emotional memory, whereas CPA at the highest dose affected acquisition and consolidation, but not retrieval of memory. Taken together, these results suggest that H1 receptor, but not H2, is implicated in anxiety-like behavior and in emotional memory acquisition and consolidation deficits in mice subjected to EPM testing.

Influência de bloqueadores H2 no processo de cicatrização gástrica

Com o objetivo de avaliar a influência de bloqueadores H2 no processo de cicatrização de lesões gástricas suturadas foram estudadas vinte cobaias machos. Após anestesia geral, laparotomia, gastrotomia de 0,5cm de extensão na parede anterior do corpo gástrico e gastrorrafia, os animais foram separados em dois grupos (GI e GII) com dez cobaias cada. As do GI receberam injeções de 0,1ml de água destilada e as do GIl 0,75mg de ranitidina, por via intramuscular, de 12/12 horas, iniciadas imediatamente após a operação e mantidas até as datas de sacrifício, realizado em número igual de cobaias, no segundo e no décimo dias de pós-operatório (PO). As peças operatórias ressecadas foram avaliadas detalhadamente. À macroscopia observou-se deiscência de sutura gástrica em um animal do GI no décimo dia de PO. A face mucosa de todas as peças apresentava enantema na linha de sutura no segundo dia de PO, porém, no décimo dia de PO o aspecto era normal, com pequena cicatriz branca no local. À microscopia, no segundo dia de PO, observou-se processo inflamatório agudo grave em ambos os grupos. No décimo dia de PO evidenciou-se inflamação moderada no GI e leve no Gil. À morfometria não houve diferença significante entre os grupos, em relação ao número de células inflamatórias, mas a densidade volumétrica de fibroblastos e de fibras colágenas foi significativamente maior no GII no décimo dia de PO. Concluiu-se que o tratamento de cobaias com bloqueadores H2 não provocou retardo da cicatrização de feridas gástricas suturadas.

Efeitos da cimetidina na resposta cronotrópica ao teste cardiopulmonar

Introdução: A histamina exerce vários efeitos no desempenho cardíaco em humanos, os quais são mediados por receptores H1e H2. A ocorrência de bradicardia e distúrbio da condução atrioventricular tem sido descrita após a injeção intravenosa de cimetidina ou ranitidina, porém ainda não foi avaliado seu potencial efeito na resposta cronotrópica ao exercício com suas implicações sobre o valor prognóstico e diagnóstico do teste de esforço Objetivo: Testar a hipótese, através de ensaio clinico randomizado, de que a administração de cimetidina altera a resposta cronotrópica ao exercício. Material e Métodos: Foram submetidos a dois testes cardiopulmonares, 20 indivíduos, após uso de placebo e de cimetidina. Os testes foram realizados em esteira rolante, com protocolo de rampa com analises diretas dos gases expirados. Foi avaliada freqüência cardíaca máxima atingida, além da freqüência cardíaca de repouso e no limiar anaeróbio. Resultados: Os indivíduos estudados estavam igualmente distribuídos por sexo, com idade média (± desvio padrão) de 43 ±11 anos. Os exames com placebo e com cimetidina tiveram igual duração (578 ± 90 seg vs 603 ± 131 seg) e igual VO2 pico (35 ± 8 ml/Kg.min vs 35 ± 8 ml/Kg.min). A administração de cimetidina não apresentou efeito significativo na freqüência cardíaca de repouso (75 ± 10 vs 74 ± 8 bpm), no pico do esforço (176 ± 12 vs176±11 bpm) e, da mesma forma, também não houve diferença entre as freqüências cardíacas de pico e de repouso (101 ± 14 vs101 ± 13 bpm). Conclusão: A administração de cimetidina por sete dias não altera a resposta cronotrópica ao exercício.

Flavoring agents present in a dentifrice can modify volatile sulphur compounds (VSCs) formation in morning bad breath

This study aimed to evaluate the effects of a flavor-containing dentifrice on the formation of volatile sulphur compounds (VSCs) in morning bad breath. A two-step, blinded, crossover, randomized study was carried out in 50 dental students with a healthy periodontium divided into two experimental groups: flavor-containing dentifrice (test) and non-flavor-containing dentifrice (control). The volunteers received the designated dentifrice and a new toothbrush for a 3 X/day brushing regimen for 2 periods of 30 days. A seven-day washout interval was used between the periods. The assessed parameters were: plaque index (PI), gingival index (GI), organoleptic breath scores (ORG), VSC levels (as measured by a portable sulphide monitor) before (H1) and after (H2) cleaning of the tongue, tongue coating (TC) wet weight and BANA test from TC samples. The intra-group analysis showed a decrease in ORG, from 3 to 2, after 30 days for the test group (p < 0.05). The inter-group analysis showed lower values in ORG, H1 and H2 for the test group (p < 0.05). There was no difference between the amount of TC between groups and the presence of flavor also did not interfere in the BANA results between groups (p > 0.05). These findings suggest that a flavor-containing dentifrice seems to prevent VSCs formation in morning bad breath regardless of the amount of TC in periodontally healthy subjects.

Proposal of abolition of the skin sensitivity test before equine rabies immune globulin application

An epizootic outbreak of rabies occurred in 1995 in Ribeirão Preto, SP, with 58 cases of animal rabies (54 dogs, 3 cats and 1 bat) confirmed by the Pasteur Institute of São Paulo, and one human death. The need to provide care to a large number of people for the application of equine rabies immune globulin (ERIG) prevented the execution of the skin sensitivity test (SST) and often also the execution of desensitization, procedures routinely used up to that time at the Emergency Unit of the University Hospital of the Faculty of Medicine of Ribeirão Preto, University of São Paulo (EU-UHFMRP-USP), a reference hospital for the application of heterologous sera. In view of our positive experience of several years with the abolition of SST and of the use of premedication before the application of antivenom sera, we used a similar schedule for ERIG application. Of the 1489 victims of animal bites, 1054 (71%) received ERIG; no patient was submitted to SST and all received intravenously anti-histamines (anti-H1 + anti-H2) and corticosteroids before the procedure. The patients were kept under observation for 60 to 180 minutes and no adverse reaction was observed. On the basis of these results, since December 1995 ERIG application has been decentralized in Ribeirão Preto and has become the responsibility of the Emergency Unit of the University Hospital and the Central Basic Health Unit, where the same routine is used. Since then, 4216 patients have received ERIG (1818 at the Basic Health Unit and 2398 at the EU-UHFMRP), with no problems. The ideal would be the routine use of human rabies immune globulin (HRIG) in public health programs, but this is problematic, because of their high cost. However, while this does not occur, the use of SST is no longer justified at the time of application of ERIG, in view of the clinical evidence of low predictive value and low sensitivity of SST involving the application of heterologous sera. It is very important to point out that a negative SST result may lead the health team to a feeling of false safety that no adverse reaction will occur, but this is not true for the anaphylactoid reactions. The decision to use premedication, which is based on knowledge about anaphylaxis and on the pharmacology of the medication used, is left to the judgment of health professionals, who should always be prepared for eventual untoward events.

Snakebites by Bothrops spp in children in Campinas, São Paulo, Brazil

From January, 1984 to March, 1999, 73 children under 15 y old (ages 1-14 y, median 9 y) were admitted after being bitten by snakes of the genus Bothrops. Twenty-six percent of the children were classified as mild envenoming, 50.7% as moderate envenoming and 20.6% as severe envenoming. Two patients (2.7%) showed no signs of envenoming. Most of the patients presented local manifestations, mainly edema (94.5%), pain (94.5%) ecchymosis (73.9%) and blisters (11%). Local and/or systemic bleeding was observed in 28.8% of the patients. Before antivenom (AV) administration, blood coagulation disorders were observed in 60.7% (incoagulable blood in 39.3%) of the 56 children that received AV only in our hospital. AV early reactions, most of which were considered mild, were observed in 44.6% of these cases (in 15/30 patients not pretreated and in 10/26 patients pretreated with hydrocortisone and histamine H1 and H2 antagonists). The main clinical complications observed were local infection (15.1%), compartment syndrome (4.1%), gangrene (1.4%) and acute renal failure (1.4%). No deaths were recorded. There were no significant differences with regard to severity of envenoming versus the frequency of blood coagulation disorders among the three categories of envenoming (p = 0.75) or in the frequency of patients with AV early reactions between the groups that were and were not pretreated (p = 0.55). The frequency of local infection was significantly greater in severe cases (p < 0.001). Patients admitted more than 6 h after the bite had a higher risk of developing severe envenoming (p = 0.04).

Snakebites by Crotalus durissus ssp in children in Campinas, São Paulo, Brazil

From January, 1984 to March, 1999, 31 children under 15 y old (ages 1-14 y, median 8 y) were admitted after being bitten by rattlesnakes (Crotalus durissus ssp). One patient was classified as "dry-bite", 3 as mild envenoming, 9 as moderate envenoming and 18 as severe envenoming. Most patients had neuromuscular manifestations, such as palpebral ptosis (27/31), myalgia (23/31) and weakness (20/31). Laboratory tests suggesting rhabdomyolysis included an increase in total blood creatine kinase (CK, 28/29) and lactate dehydrogenase (LDH, 25/25) levels and myoglobinuria (14/15). The main local signs and symptoms were slight edema (20/31) and erythema (19/31). Before antivenom (AV) administration, blood coagulation disorders were observed in 20/25 children that received AV only at our hospital (incoagulable blood in 17/25). AV early reactions were observed in 20 of these 25 cases (9/9 patients not pretreated and 11/16 patients pretreated with hydrocortisone and histamine H1 and H2 antagonists). There were no significant differences in the frequency of patients with AV early reactions between the groups that were and were not pretreated (Fisher's exact test, p = 0.12). Patients admitted less than and more than 6 h after the bite showed the same risk of developing severe envenoming (Fisher's exact test, p = 1). No children of the first group (< 6 h) showed severe complications whereas 3/6 children admitted more than 6 h post-bite developed acute renal failure. Patients bitten in the legs had a higher risk of developing severe envenoming (Fisher's exact test, p = 0.04). There was a significant association between both total CK and LDH blood enzyme levels and severity (p < 0.001 for CK and p < 0.001 for LDH; Mann-Whitney U test). No deaths were recorded.

Diversity of Trypanosoma cruzi stocks and clones derived from Chagas disease patients: I-Behavioral characterization in vitro

In this study, we isolated Trypanosoma cruzi from chronic Chagas heart disease and from megaesophagus patients. The parasite stock hSLU239 (heart disease) yielded clones h1 and h2, whereas stock mSLU142 (megaesophagus) yielded clones m1, m2, m3 and m4. The parasite growth kinetics, doubling time and differentiation in axenic liquid medium showed broad behavioral diversity. It was shown that a particular pattern of behavior for a parental stock could not necessarily be assigned for subsequent clones. This study indicates that i) each Chagas disease patient is infected with several T. cruzi populations; ii) clonal lines derived from patient samples may have different biological characteristics from the original isolate; and that iii) additional behavioral and/or molecular markers are required for further characterization of Trypanosoma cruzi stocks and clones derived from Chagas disease patients in order to identify correlations with pathology.

Caracterização funcional da hipertrofia miocárdica induzida pelo isoproterenol e de sua regressão

OBJETIVO: Analisar as disfunções da hipertrofia miocárdica induzida pelo isoproterenol e de sua regressão. Corações isolados hipertrofiados por isoproterenol (ISO) (8 dias) e após 22 dias de sua suspensão (regressão) foram distendidos. MÉTODOS: Até pressão de repouso (Pr) de 60mmHg, analisaram-se: pressão desenvolvida máxima (PDmáx.); estresse sistólico (sigmamáx); inclinação da reta estresses/deformações; constante de relaxamento; rigidez da câmara e rigidez miocárdica. RESULTADOS: Nos corações hipertrofiados (H) as variações de volume (deltaV) necessárias para Pr=60mmHg foram heterogêneas. Em alguns (H1; n=10) deltaV equivaleu à dos controle (C) enquanto em outros (H2; n=10) foi inferior, e também diferiram quanto ao peso seco, complacência ventricular, rigidez miocárdica, constante de relaxamento,e sigmamáx. PDmáx dos grupos H1 e H2 foram superiores às de C (n=8) e Regressão (R) (n=8). Contudo, sigmamáx de H2 foi menor que C, H1 e R. O mecanismo de Frank-Starling foi deprimido nos corações hipertrofiados. A constante de relaxamento de H2 indicou retardo no decaimento da pressão associado a menor complacência ventricular e rigidez miocárdica acentuada. CONCLUSÃO: Hipertrofia miocárdica induzida pelo ISO não é homogênea. Alguns corações têm alterações pouco expressivas; outros têm comprometimento das funções sistólica e diastólica. A hipertrofia miocárdica reduz a capacidade de gerar força e aprimora a capacidade em variar pressão por aumento da relação massa/volume. Há, também, comprometimento da complacência ventricular e da rigidez muscular.