Phallus eversion sexing in Phrynops geoffroanus (Testudines: Chelidae): a new non-invasive approach / Sexagem por eversão do falo em Phrynops geoffroanus (Testudines: Chelidae): uma nova abordagem não invasiva

Abstract The sexing of species is an important tool for population management. In tortoises and turtles, sexing is usually done according to secondary characteristics, such as plastron morphology or phallus eversion techniques. In this paper, we present the phallus eversion method and compare its efficiency to other existing techniques. This new method aims at shortening the management time and reducing the physical aftereffects on the animals, fostering the clinical and reproductive management of Geoffroy's side-necked turtle (Phrynops geoffroanus) and related species. A sample of fifty individuals was taken in the central region of Piauí state, Northeastern Brazil. The proposed method consisted of moving the head from its resting position. The methods achieving a success rate higher than 80% were compared to each other as for the stimulation time required for phallus eversion. The method as here proposed achieved 100% efficiency in the sex determination of specimens with a linear carapace length between 10 and 34 cm. Also, when compared to the second most efficient method, it substantially reduced the time needed for managing the specimens (91%), avoiding possible sequelae in the individuals handled.

Resumo A sexagem das espécies é uma ferramenta importante para o manejo populacional. Em tartarugas, cágados e jabutis, a sexagem geralmente é feita de acordo com características secundárias, como morfologia do plastrão ou técnicas de eversão do falo. Neste artigo, apresentamos o método de eversão do falo e comparamos sua eficiência com outras técnicas existentes. Este novo método visa encurtar o tempo de manejo e reduzir os efeitos colaterais físicos nos animais, promovendo o manejo clínico e reprodutivo do cágado-de-barbicha (Phrynops geoffroanus) e espécies relacionadas. Uma amostra de cinquenta indivíduos foi coletada na região central do estado do Piauí, Nordeste do Brasil. O método proposto consiste em remover a cabeça de sua posição de repouso. Os métodos que obtiveram índice de sucesso superior a 80% foram comparados entre si quanto ao tempo de estimulação necessário para a eversão do falo. O método aqui proposto alcançou 100% de eficiência na determinação do sexo de espécimes com comprimento de carapaça linear entre 10 e 34 cm. Além disso, quando comparado ao segundo método mais eficiente, reduziu substancialmente o tempo necessário para o manejo dos espécimes (91%), evitando possíveis sequelas nos indivíduos manuseados.

Phallus eversion sexing in Phrynops geoffroanus (Testudines: Chelidae): a new non-invasive approach

Abstract The sexing of species is an important tool for population management. In tortoises and turtles, sexing is usually done according to secondary characteristics, such as plastron morphology or phallus eversion techniques. In this paper, we present the phallus eversion method and compare its efficiency to other existing techniques. This new method aims at shortening the management time and reducing the physical aftereffects on the animals, fostering the clinical and reproductive management of Geoffroys side-necked turtle (Phrynops geoffroanus) and related species. A sample of fifty individuals was taken in the central region of Piauí state, Northeastern Brazil. The proposed method consisted of moving the head from its resting position. The methods achieving a success rate higher than 80% were compared to each other as for the stimulation time required for phallus eversion. The method as here proposed achieved 100% efficiency in the sex determination of specimens with a linear carapace length between 10 and 34 cm. Also, when compared to the second most efficient method, it substantially reduced the time needed for managing the specimens (91%), avoiding possible sequelae in the individuals handled.

Resumo A sexagem das espécies é uma ferramenta importante para o manejo populacional. Em tartarugas, cágados e jabutis, a sexagem geralmente é feita de acordo com características secundárias, como morfologia do plastrão ou técnicas de eversão do falo. Neste artigo, apresentamos o método de eversão do falo e comparamos sua eficiência com outras técnicas existentes. Este novo método visa encurtar o tempo de manejo e reduzir os efeitos colaterais físicos nos animais, promovendo o manejo clínico e reprodutivo do cágado-de-barbicha (Phrynops geoffroanus) e espécies relacionadas. Uma amostra de cinquenta indivíduos foi coletada na região central do estado do Piauí, Nordeste do Brasil. O método proposto consiste em remover a cabeça de sua posição de repouso. Os métodos que obtiveram índice de sucesso superior a 80% foram comparados entre si quanto ao tempo de estimulação necessário para a eversão do falo. O método aqui proposto alcançou 100% de eficiência na determinação do sexo de espécimes com comprimento de carapaça linear entre 10 e 34 cm. Além disso, quando comparado ao segundo método mais eficiente, reduziu substancialmente o tempo necessário para o manejo dos espécimes (91%), evitando possíveis sequelas nos indivíduos manuseados.

Efeito do hipotireoidismo materno na expressão espaço-temporal de mediadores imunológicos e população de células natural killers na decídua e na glândula metrial de ratas / Effect of maternal hypothyroidism on the spatiotemporal expression of immunological mediators and population of Natural Killers cells in decidua and metrial gland of rats

Estudou-se o efeito do hipotireoidismo materno na expressão espaço-temporal de mediadores imunológicos e na população de células natural killers (NK) na decídua e na glândula metrial de ratas durante a gestação. Avaliou-se a detecção imunoistoquímica de interferon γ (IFNγ), do fator inibidor de migração (MIF), da interleucina 15 (IL15), do óxido nítrico sintase induzível (iNOS), a marcação com lectina DBA para evidenciação das células NK uterinas DBA+ e a expressão gênica de Ifnγ e Nos2. O hipotireoidismo aumentou o iNOS aos sete dias, a IL15 e o MIF aos 10 e 12 dias, o IFNγ e o MIF aos 14 DG e a expressão dos transcritos gênicos para iNos aos 12 e 19 dias e para Ifnγ aos 14 DG. O hipotireoidismo reduziu a imunomarcação de MIF e lectina DBA aos sete dias, lectina DBA aos 10 e 14 DG, IFNγ aos 12 dias, e a expressão de Ifnγ aos 10 e 19 DG e de iNOS aos 12, 14 e 19 DG, bem como reduziu seus transcritos gênicos aos 10 e 14 DG. Conclui-se que o hipotireoidismo compromete o perfil imunológico na interface materno-fetal ao longo da gestação, particularmente por reduzir o fator anti-inflamatório iNOS e a população de células uNK DBA+.(AU)

The goal of this study was to evaluate the effect of maternal hypothyroidism on the spatiotemporal expression of immunological mediators and population of Natural Killers cells in decidua and metrial gland of rats. Interferon gamma (IFNγ), migration inhibitory factor (MIF), interleukin 15 (IL15), inducible nitric oxide synthase (iNOS), and DBA-Lectin labeling for evidence of uNK DBA+ cells in decidua and genetic expression of Ifnγ and iNos by real-time RT-PCR were evaluated. Hypothyroidism increased protein expression of iNOS at 7 days, IL15 and MIF at 10 and 12 days, IFNγ and MIF at 14 DG in the decidua and/or metrial gland and the gene transcripts for iNOS at 12 and 19 days and for Inf at 14 DG. In addition, hypothyroidism reduced the protein expression of MIF and DBA-Lectin at 7 days, DBA-Lectin at 10 and 14 DG, IFNγ at 12 days, and the gene transcript to Ifnγ at 10 and 19 DGs. Hypothyroidism also reduced the protein expression of iNOS at 12, 14 and 19 DG and reduced its gene transcripts at 10 and 14 DGs. It is concluded that hypothyroidism compromises the immunology profile at the maternal-fetal interface throughout pregnancy, particularly by reducing the anti-inflammatory factor iNOS and population of uNK DBA+ cells.(AU)

Estimation of a closed population size of tadpoles in temporary pond / Estimativa do tamanho da população fechada de girinos em lagoas temporárias

Abstract The practice of capture-recapture to estimate the diversity is well known to many animal groups, however this practice in the larval phase of anuran amphibians is incipient. We aimed at evaluating the Lincoln estimator, Venn diagram and Bayes theorem in the inference of population size of a larval phase anurocenose from lotic environment. The adherence of results was evaluated using the Kolmogorov-Smirnov test. The marking of tadpoles for later recapture and methods measurement was made with eosin methylene blue. When comparing the results of Lincoln-Petersen estimator corresponding to the Venn diagram and Bayes theorem, we detected percentage differences per sampling, i.e., the proportion of sampled anuran genera is kept among the three methods, although the values are numerically different. By submitting these results to the Kolmogorov-Smirnov test we have found no significant differences. Therefore, no matter the estimator, the measured value is adherent and estimates the total population. Together with the marking methodology, which did not change the behavior of tadpoles, the present study helps to fill the need of more studies on larval phase of amphibians in Brazil, especially in semi-arid northeast.

Resumo A prática de captura-recaptura para a estimação da diversidade é bem conhecida para diversos grupos animais, porém na fase larvar de anfíbios anuros essa prática é incipiente. Objetivamos avaliar os métodos do estimador de Lincoln, diagrama de Venn e o teorema de Bayes na inferência do tamanho populacional de uma anurocenose em fase larvar de ambiente lótico. A aderência dos resultados foi avaliada através do teste de Kolmogorov-Smirnov. A marcação dos girinos para posterior recaptura e aferição dos métodos foi feita com eosina de azul de metileno. Ao compararmos os resultados do estimador de Lincoln que corresponde com o do diagrama de Venn e com o teorema de Bayes detectamos diferenças percentuais por amostragem, isto é, a manutenção da proporção dos gêneros de anuros amostrados é mantida entre os três métodos, embora com valores numericamente diferentes. Ao submetermos esses resultados ao teste Kolmogorov-Smirnov não encontramos diferenças significativas. Logo, qualquer que seja o estimador o valor aferido é aderente e estima a população total. Aliado à metodologia de marcação que não alterou o comportamento dos girinos, o presente estudo ajuda a preencher a necessidade de mais estudos na fase larvar dos anfíbios no Brasil, em especial no semiárido nordestino.

Induction and growth pattern of callus from Piper permucronatum leaves / Indução e padrão de crescimento de calos de folhas de Piper permucronatum

ABSTRACT Piper permucronatum is a perennial shrub, a medicinal plant native to the Amazon Rainforest. Traditionally, the tea of its leaves is used to combat menstrual and intestinal cramps, stomach pain, digestive problems, diarrhea, hemorrhage, and nausea. Its leaf’s essential oil is effective against Aedes aegypti larvae; its flavones and flavanones have a fungicidal effect against Clamidosporium cladosporioides and C. sphaerospermum; its hexanic extract is effective against Leishmania amazonensis. The objective of this study was to provide a protocol for callus induction from P. permucronatum leaves and an identification of the callus growth pattern, focusing on the deceleration phase, when the callus cells must be subcultured into liquid medium in order to produce a cell suspension cultures. Leaf explants were inoculated in a solid MS medium supplemented with factorial combinations of 2,4-D, BA, NAA and GA3. Callus formation was evaluated weekly until the 49th day. Subsequently, new explants were inoculated at the hormonal combination that resulted in the highest callus cell proliferation and, every seven days during a period of 70 days, samples were dried and weighed to determine the callus growth pattern. NAA and GA3 were not effective for callus induction. Combinations of 2,4-D and BA resulted in callus induction and proliferation. The highest percentage of callus induction was observed with the combination of 4.52 µM 2,4-D and 4.44 µM BA. The calluses thereby produced were friable and whitish. The callus growth pattern followed a sigmoid shape. The deceleration phase started on the 56th day of culture.

RESUMO Indução e padrão de crescimento de calos de folhas de Piper permucronatum. Piper permucronatum é um arbusto perene, uma planta medicinal native da Floresta Amazônica. Tradicionalmente, o chá de suas folhas é usado em casos de cólicas menstruais e intestinais, dores de estômago, problemas digestivos, diarreia, hemorragia e náusea. O óleo essencial das folhas é efetivo contra a larva de Aedes aegypti; suas flavonas e flavanonas têm efeito fungicida contra Clamidosporium cladosporioides e C. sphaerospermum; seu extrato hexânico é efetivo contra Leishmania amazonensis. O objetivo deste trabalho foi determinar um protocolo para indução de calos em folhas de P. permucronatum e identificar o padrão de crescimento dos calos, com foco na fase de desaceleração, quando as células de calo devem ser subcultivadas em meio líquido para produzir culturas de células em suspensão. Explantes foliares foram inoculados em meio MS sólido suplementado com combinações fatoriais de 2,4-D, BAP, ANA e GA3. A formação de calos foi avaliada semanalmente até o 49º dia. Posteriormente, novos explantes foram inoculados na combinação hormonal que resultou na maior proliferação de células de calo e, a cada sete dias durante 70 dias, amostras foram secas e pesadas para determinar o padrão de crescimento dos calos. ANA e GA3 não foram efetivas para a indução de calos. Combinações de 2,4-D e BAP resultaram em indução e proliferação de calos. A maior porcentagem de indução de calos foi observada com a combinação de 4,52 µM de 2,4-D e 4,44 µM de BAP. Os calos produzidos eram friáveis e esbranquiçados. O crescimento dos calos seguiu um padrão sigmoide. A fase de desaceleração iniciou no 56º dia de cultivo.

Efeito de diferentes meios nutritivos e fitorreguladores visando à otimização da calogênese de Annona mucosa (Jacq. ) / Effect of different culture media and plant growth regulators for the optimization of callus induction of Annona mucosa (Jacq. )

Annona mucosa é uma árvore frutífera da família Annonaceae, produtora de importantes metabólitos secundários de interesse medicinal, como lignanas, acetogeninas e alcaloides. A cultura in vitro de calos representa um importante recurso para a produção contínua de metabólitos, viabilizando a conservação da biodiversidade química e a obtenção controlada de material para estudos biológicos e fitoquímicos. O objetivo deste trabalho foi otimizar a produção de calos friáveis de A. mucosa, avaliando o efeito de diferentes meios nutritivos e fitorreguladores. Segmentos de folha e de hipocótilo de plântulas germinadas in vivo foram utilizados como explantes e inoculados nos meios de cultura MS, WPM e B5 suplementados com picloram (2 - 20µM) isolado ou combinado com as citocininas BAP, KIN ou TDZ (0,2 - 1µM). As culturas foram mantidas a 26±2ºC, no escuro, com subcultivos mensais. A produção de calos foi avaliada por aferição do peso dos calos, após 90 dias. Em todos os tratamentos na presença da auxina picloram, o cultivo de hipocótilos resultou em maior porcentagem de formação de calos, sobretudo no meio de cultura WPM. A associação com TDZ produziu massa calogênica friável altamente proliferativa e ausente de oxidação, alcançando valores superiores àqueles obtidos em trabalhos prévios com a espécie. Os resultados viabilizam o uso do material em suspensões celulares e posterior caracterização fitoquímica para a exploração da produção in vitro de metabólitos da espécie.

The Annona mucosa is a fruit tree of the Annonaceae family that produces a range of secondary metabolites of medicinal interest, such as lignans, acetogenins and alkaloids. The callus culture represents a renewable source of valuable medicinal compounds and controlled supply of material for biological and phytochemical studies. Therefore, this study was carried out to investigate the effects of three nutrient media, different concentrations of picloram and cytokinin types, in order to optimize the biomass yield and friability of calluses of A. mucosa. Leaf and hypocotyl segments from seedlings produced from in vivo seed germination were used as explants, which were inoculated in MS, WPM and B5 culture media supplemented with picloram (2-20µM) only or in addition to the cytokinins BAP, KIN or TDZ (0,2 - 1µM ). Cultures were maintained at 26±2ºC in the dark, with monthly subcultures. After 90 days, biomass production was evaluated. In all treatments, hypocotyl explants provided the highest percentage of callus formation, particularly in WPM. The association with TDZ produced highly proliferative friable callus, with no oxidation, reaching higher values than the previous works with this species. The results enable the use of the calluses produced in cell suspensions and the subsequent phytochemical characterization, in order to explore the in vitro production of metabolites of the species.

Peritoneal and serum interleukin-18 levels are not increased in women with minimum or mild endometriosis

Interleukin-18 (IL-18) is a cytokine that belongs to the IL-1 family. Endometriosis is strongly associated with sub-fertility, and affects about 15 percent of women of reproductive age. IL-18 may favor the progression of endometriosis. The objective of the present study was to determine the concentration of IL-18 in the serum and peritoneal fluid of infertile women with endometriosis. Forty infertile and 25 fertile women were screened in a teaching hospital. Thirty-four infertile patients with minimal or mild endometriosis and 22 fertile controls were enrolled in the study. The primary outcome was the estimate of IL-18 levels and the secondary outcome was the correlation between serum and peritoneal levels of IL-18. There were no differences between the two groups regarding age, body mass index and levels of peritoneal fluid IL-18 (mean ± SD): 290.85 ± 173.02 pg/mL for infertile women vs 374.21 ± 330.15 pg/mL for controls; or serum IL-18: 391.07 ± 119.71 pg/mL for infertile women vs 373.42 ± 129.11 pg/mL for controls. However, a positive association was found between serum and peritoneal IL-18 levels in patients with endometriosis: r = 0.794, P = 0.0001. All measurements were carried out at the same time by the Human IL-18 Immuno Assay ELISA kit (MBL Co. Ltd., Japan). The present study did not find evidence supporting the hypothesis that IL-18 levels are associated with infertility in women with minimal and mild endometriosis, although a positive correlation was detected in these women between peritoneal and serum levels of IL-18.

Low expression of APAF-1XL in acute myeloid leukemia may be associated with the failure of remission induction therapy

Apoptotic protease activating factor 1 (APAF-1) has a critical role in the regulation of apoptosis. In the present study, the mRNA expression analysis of different APAF-1 transcripts (APAF-1S, APAF-1LC, APAF-1LN, and APAF-1XL) was analyzed in bone marrow samples from 37 patients with acute myeloid leukemia (newly diagnosed, with no previous treatment). APAF-1XL and APAF-1LN transcripts (with and without an extra WD-40 repeat region, respectively) were detected in all samples, although the major form expressed was APAF-1XL in 65 percent of the samples (group 1), while 35 percent of the samples expressed primarily APAF-1LN (group 2). Only 46 percent of the patients presented complete remission in response to remission induction therapy (represented by less than 5 percent marrow blasts and hematological recovery), all but 2 cases being from group 1, 21.6 percent did not attain complete remission (only 1 case from group 1), and 32.4 percent of the patients died early. Lower expression of APAF-1XL (APAF-1XL/APAF-1LN ratio <1.2) was associated with a poor response to therapy (P = 0.0005, Fisher exact test). Both groups showed similar characteristics regarding white blood cell counts, cytogenetic data or presence of gene rearrangements associated with good prognosis as AML1-ETO, CBFB-MYH11 and PML/RARA. Since it has been shown that only the isoforms with the extra WD-40 repeat region activate procaspase-9, we suggest that low procaspase-9 activation may also be involved in the deregulation of apoptosis and chemotherapy resistance in acute myeloid leukemia.

Uretrostomia para colheita seriada de urina em bezerros / Urethrostomy for serial sampling of urine in calves

Urethrostomy for serial sampling of urine was used due to the necessity of one technique that allowed the total urinary collection in definite time periods. Twenty-seven male Holstein calves from 8 to 16-days-age having a mean weight 39.50±4.80kg were used. Urethrostomy was carried out with the use of urethral sounding lead that was made for this purpose. In agreement with the clinical examinations, including seric biochemical, urinalysis and blood test and postmortem examination, the technique achieved 81.5 percent of satisfactory results.

The availability of full match sibling donors and feasibility of allogeneic bone marrow transplantation in Brazil

The feasibility of allogeneic bone marrow transplantation (alloBMT) in a developing country has not yet been demonstrated. Many adverse factors including social and economic limitations may reduce the overall results of this complex and expensive procedure. Our objective was to characterize the most important clinical, social and economic features of candidates for transplantation and their potential donors as well as the influence of these factors on overall survival in a retrospective and exploratory analysis at a university hospital. From July 1993 to July 2001, candidates for BMT were referred to the Bone Marrow Transplantation Unit by Hematology and Oncology Centers from several regions of Brazil. A total of 1138 patients were referred to us as candidates for alloBMT. Median age was 25 years (range: 2 months-60 years), 684 (60.1 percent) were males and 454 (39.9 percent) were females. The clinical indications were severe aplastic anemia and hematological malignancies. From the total of 1138 patients, 923 had HLA-typing; 497/923 (53.8 percent) candidates had full match donors; 352/1138 (30.8 percent) were eligible for alloBMT. Only 235 of 352 (66.7 percent) were transplanted. Schooling was 1st to 8th grade for 123/235 (52.3 percent); monthly family income ranged from US$60 (7 percent) to more than US$400 (36 percent). Overall survival for patients with chronic myeloid leukemia, severe aplastic anemia and acute myeloid leukemia was 58, 60 and 30 percent, respectively. Thus, overall survival rates for the most frequent hematological diseases were similar to those reported in the International Registry, except for acute myeloid leukemia. This descriptive and exploratory analysis suggests the feasibility of alloBMT in a developing country like Brazil

Sex in fungi: lessons of gene regulation

Fungi have been very useful for gene regulation studies. Mating implicates in a series of events influenced by many types of environmental input that are interpreted into regulatory pathways, including signal transduction. Although various aspects of mating and signal transduction in the yeast Saccharomyces cerevisiae have long been characterized, recent findings in filamentous fungi indicate that pheromones and pheromone receptors may be essential for mating partner recognition and also for nucleus recognition in sorting before meiosis. A brief overview on mating-type genes of ascomycete fungi and recent contributions to the understanding of their role in the regulation of multicellularity and sexual dimorphism is presented in this review

Autologous stem cell transplantation for aggressive non-Hodgkin's lymphomas

O transplante autólogo de célula progenitora ou medula óssea (ATMO) tem demonstrado capacidade de superar resistência tumoral através da elevação da intensidade de dose de drogas disponíveis e radioterapia. ATMO foi inicialmente utilizado em LNH após recidiva em primeira linha ou refratários. ATMO tem demonstrado maior utilidade em condições clínicas mais favoráveis como na remissão parcial (RP), primeira remissão completa (RC) e como primeira linha após quimioterapia. Quimioterapia de alta dose e ATMO se tornaram a terapêutica standard para pacientes elegíveis com LNH agressivo, recorrente e quimiosensível. Pacientes primariamente refratários e com recidiva resistente não são boas indicações e devem ser considerados como grupo elegível para estudos de fase II. Talvez, haja um papel do ATMO em pacientes parcialmente responsivos. Entretanto, novos e grandes estudos randomizados são necessários para esclarecer esta questão. Um desafio para o manuseio dos linfomas é a definição da terapia de alta dose seguida do ATMO como terapêutica inicial para os LNH agressivos, identificando pacientes que não possam ser curados com terapêutica convencional. Uma série de estudos retrospectivos ou controlados parece indicar os chamados pacientes de "alto-risco", definido pela IPI como potencial alvo destas terapêuticas intensificadas. Entretanto, de acordo com dados publicados, o problema permanece aberto para debates. Estudos grandes e randomizados são necessários e bem vindos e devem ser considerados prioridade neste campo da ciência médica.

Correlation of mixed lymphocyte culture with chronic graft-versus-host disease following allogeneic stem cell transplantation

The purpose of the present study was to evaluate the mixed lymphocyte culture as a predictive assay of acute and chronic graft-versus-host disease (GVHD). We studied 153 patients who received a first bone marrow transplantation from human leukocyte antigen-identical siblings. Acute GVHD was observed in 26 of 128 (20.3 percent) patients evaluated and chronic GVHD occurred in 60 of 114 (52.6 percent). One-way mixed lymphocyte culture (MLC) assays were performed by the standard method. MLC results are reported as the relative response (RR) from donor against patient cells. The responses ranged from -47.0 to 40.7 percent, with a median of 0.5 percent. The Kaplan-Meier probability of developing GVHD was determined for patients with positive and negative MLC. There was no significant difference in incidence of acute GVHD between the groups studied. However, the incidence of chronic GVHD was higher in recipients with RR >4.5 percent than in those with RR <=4.5 percent. The Cox Proportional Hazards model was used to examine the effect of MLC levels on incidence of chronic GVHD, while adjusting for the potential confounding effect of others suspected or observed risk factors. The relative risk of chronic GVHD was 2.5 for patients with positive MLC (RR >4.5 percent), 2.9 for those who received peripheral blood progenitor cells as a graft, and 2.2 for patients who developed previous acute GVHD. MLC was not useful for predicting acute GVHD, but MLC with RR >4.5 percent associated with other risk factors could predict the development of chronic GVHD, being of help for the prevention and/or treatment of this late complication

High-dose cyclophosphamide followed by autologous peripheral blood progenitor cell transplantation improves the salvage treatment for persistent or sensitive relapsed malignant lymphoma

Trials have demonstrated that high-dose escalation followed by autologous transplantation can promote better long-term survival as salvage treatment in malignant lymphomas. The aim of the present nonrandomized clinical trial was to demonstrate the role of high-dose cyclophosphamide (HDCY) in reducing tumor burden and also to determine the effectiveness of HDCY followed by etoposide (VP-16) and methotrexate (MTX) in Hodgkin's disease plus high-dose therapy with peripheral blood progenitor cell (PBPC) transplantation as salvage treatment. From 1998 to 2000, 33 patients with a median age of 33 years (13-65) affected by aggressive non-Hodgkin's lymphoma (NHL) (60.6 percent) or persistent or relapsed Hodgkin's disease (39.4 percent) were enrolled and treated using high dose escalation (HDCY + HDVP-16 plus HDMTX in Hodgkin's disease) followed by autologous PBPC transplantation. On an "intention to treat" basis, 33 patients with malignant lymphomas were evaluated. The overall median follow-up was 400 days (40-1233). Thirty-one patients underwent autografting and received a median of 6.19 x 10(6)/kg (1.07-29.3) CD34+ cells. Patients who were chemosensitive to HDCY (N = 22) and patients who were chemoresistant (N = 11) presented an overall survival of 96 and 15 percent, respectively (P<0.0001). Overall survival was 92 percent for chemosensitive patients and 0 percent for patients who were still chemoresistant before transplantation (P<0.0001). Toxicity-related mortality was 12 percent (four patients), related to HDCY in two cases and to transplant in the other two. HDCY + HDVP-16 plus HDMTX in only Hodgkin's disease followed by autologous PBPC proved to be effective and safe as salvage treatment for chemosensitive patients affected by aggressive NHL and Hodgkin's disease, with acceptable mortality rates related to sequential treatment

Amifostine (WR-2721), a cytoprotective agent during high-dose cyclophosphamide treatment of non-Hodgkin's lymphomas: a phase II study

Clinical trials indicate that amifostine may confer protection on various normal tissues without attenuating anti-tumor response. When administered prior to chemotherapy or radiotherapy, it may provide a broad spectrum of cytoprotection including against alkylating drugs. The mechanism of protection resides in the metabolism at normal tissue site by membrane-bound alkaline phosphatase. Toxicity of this drug is moderate with hypotension, nausea and vomiting, and hypocalcemia being observed. We report a phase II study using amifostine as a protective drug against high-dose cyclophosphamide (HDCY) (7 g/m2), used to mobilize peripheral blood progenitor cells (PBPC) and to reduce tumor burden. We enrolled 29 patients, 22 (75.9 percent) affected by aggressive and 7 (24.1 percent) by indolent non-Hodgkin's lymphoma (NHL), who were submitted to 58 infusions of amifostine and compared them with a historical group (33 patients) affected by aggressive NHL and treated with VACOP-B followed by HDCY. The most important results in favor of amifostine were the reduction of intensity of cardiac, pulmonary and hepatic toxicity, and a significant reduction of frequency and severity of mucositis (P = 0.04). None of the 29 patients died in the protected group, while in the historical group 2/33 patients died because of cardiac or pulmonary toxicity and 2 patients stopped therapy due to toxicity. Amifostine did not prevent the aplastic phase following HDCY. PBPC collection and hematological recovery were adequate in both groups. The number of CFU-GM (colony-forming units-granulocyte/macrophage) colonies and mononuclear cells in the apheresis products was significantly higher in the amifostine group (P = 0.02 and 0.01, respectively). Side effects were mild and easily controlled. We conclude that amifostine protection should be useful in HDCY to protect normal tissues, with acceptable side effects.

Study of the effects of ß-myrcene on rat fertility and general reproductive performance

Beta-Myrcene (MYR) is a monoterpene found in the oils of a variety of aromatic plants including lemongrass, verbena, hop, bay, and others. MYR and essential oils containing this terpenoid compound are used in cosmetics, household products, and as flavoring food additives. This study was undertaken to investigate the effects of MYR on fertility and general reproductive performance in the rat. MYR (0, 100, 300 and 500 mg/kg) in peanut oil was given by gavage to male Wistar rats (15 per dose group) for 91 days prior to mating and during the mating period, as well ass to females (45 per dose group) continuously for 21 days before mating, during mating and pregnancy, and throughout the period of lactatiomn up to postnatal day 21. On day 21 of pregnancy one-third of the females of each group were submitted to cesarean section. Resorption, implantation, as well as dead and live fetuses were counted. All fetuses were examined for external malformation, weighed, and cleared and stained with Alizarin Red S for skeleton evaluation. The remaining dams were allowed to give birth to their offspring. The progeny was examined at birth and subsequently up to postnatal day 21. Mortality, weight gain and physical signs of postnatal development were evaluated. Except for an increase in liver and kidney weights, no other sign of toxicity was noted in male and female rats exposed to MYR. MYR did not affect the mating index (proportion of females impregnated by males) or the pregnancy index (ratio of pregnant to sperm-positive females). No sign of maternal toxicity and no increase in externally visible malformations were observed at any dose level. Only at the highest dose tested (500 mg/kg) did MYR induce an increase in the resorption rate and a higher frequency of fetal skeleton anomalies. No adverse effect of MYR on postnatal weight gain was noted but days of appearance of primary coat, incisor eruption and eye opening were slightly delayed in the exposed offspring. On the basis of the data presented in this paper the no-observed-adverse-effect level (NOAEL) for toxic effects on fertility and general reproductive performance can be set at 300 mg of Beta-myrcene/kg body weight by the oral route.

Study of the embryofeto-toxicity of Crown-of-Thorns (Euphorbia milii) latex, a natural molluscicide

The crude latex of Crown-of-Thorns (Euphorbia milii var. Hislopii) is a potent plant molluscicide and a promising alternative to the synthetic molluscicides used in schistosomiasis control. The present study was undertaken to investigate the embryofeto-toxic potential of E. Milii latex. The study is part of a comprehensive safety evaluation of this plant molluscicide. Lyophilized latex (0, 125, 250 and 500 mg/kg body weight) in corn oil was given by gavage to Wistar rats (N = 100) from days 6 to 15 of pregnancy and cesarean sections were performed on day 21 of pegnancy. The numbers of implantation sites, living and dead fetuses, resorptions and corpora lutea were recorded. Fetuses were weighed, examined for external malformations, and fixed for visceral examination, or cleared and stained with Alizarin red S for skeleton evaluation. A reduction of body weight minus uterine weight al term indicated that E. Milii latex was maternally toxic over the dose range tested. No latex-induced embryolethality was noted at the lowest dose (125 mg/kg) but the resorption rate was markedly increased at 250 mg/kg (62.5 percent) and 500 mg/kg (93.4 percent). A higher frequency of fetuses showing signs of delayed ossification (control: 17.4 percent; 125 mg/kg: 27.4 percent and 250 mg/kg: 62.8 percent; P<0.05 vs control) indicated that fetal growth was retarded at doses ³125 mg latex/kg body weight. No increase in the proportion of fetuses with skeletal anomalies was observed at the lowest dose but the incidence of minor skeletal malformations was higher at 250 mg/kg body weight (control: 13.7 percent; 125 mg/kg: 14.8 percent; 250 mg/kg: 45.7 percent; P<0.05 vs control). Since a higher frequency of minor malformations was noted only at very high doses of latex which are embryolethal and maternally toxic, it is reasonable to conclude that this plant molluscicide poses no teratogenic hazard or, at least, that this possibility is of a considerably low order of magnitude.

A descoberta da imipramina e a psicoterapia: uma (re)visäo / Imipramine's discovery and the psychotherapy: a (re)vision

Duas conferências de ROLAND KUHN, pronunciadas em 1972 e 1977, respectivamente, em Belo Horizonte e Barcelona foram (re)vistas. Através das mesmas é evidenciado como a descoberta da imipramina, nas suas origens, esteve entimamente relacionada com a psicoterapia. Também é mostrado como KUHN utilizou alguns argumentos de FREUD a respeito de uma relaçao especial entre neurose e depressao, neurose e regressao e sobre as substâncias químicas responsáveis pela distribuiçao de energia no aparelho psíquico. Ao mesmo tempo, como referiu-se ao conceito de "depressao vital", enunciado por BINSWANGER, como o grande motivador conceitual ou teórico da descoberta da imipramina através da análise existencial. Ainda através do texto sao expostos argumentos de KUHN favoráveis ao emprego conjunto de psicoterapia e psicofarmacoterapia. Como enriquecimento aos argumentos do psiquiatra suíco favorável aos tratamentos combinados foram utilizadas idéias de outros autores que os consubstanciam. A (re)visao permitiu verificar que: 1) a relaçao íntima entre o emprego da imipramina e a psicoterapia é um texto histórico essencial ao conhecimento; 2) os textos de KUHN se mostram muito atuais à psiquiatria brasileira; 3) o reducionismo nesta área de grande complexidade - frente a ausência de conhecimentos mais completos - é inútil e ilógico. Como conclusao, sao considerados a origem e o tempo da descoberta da imipramina e levantadas questoes a respeito da demora no reconhecimento de textos essenciais do conhecimento psiquiátrico.

Embryotoxic effects of misoprostol in the mouse

Misoprostol (MSP) is a synthetic prostaglandin E1 methyl analogue indicated for the prevention of gastric ulcers induced by nonsteroidal anti-inflammatory drugs (NSAIDs). Because of its abortifacient properties, MSP has been extensively missused for abortion induction in Brazil. Since abortion induction with MSP very often fails and pregnancy continues to term, there has been increasing concern regarding the potential teratogenicity of this PGE1 analogue in humans. The objective of the present study was to evaluate the embryotoxicity of MSP in mice. A single dose of MSP(20 or 30 mg/kg body weight) was administered to Han:NMRI mice (ca 60 days old) by gavage on day 10 of pregnancy. The number of treated mice was as follows: control, 19; MSP 20 mg/kg, 10; MSP 30 mg/kg, 28. Cesarean sections were performed on day 18 of pregnancy and the number of resorptions and implantation sites were recorded. Fetuses were weighed, examined for external malformations, fixed, cleared and stained with Alizarin Red S for skeleton evaluation. No evidence of embryotoxicity was found at the lower dose tested. A slight and reversible deficit in pregnancy weight gain ...