Central Pain in Parkinson's Disease: Behavioral and Cognitive Characteristics.

INTRODUCTION: Pain is a major nonmotor symptom of Parkinson's disease (PD), and central parkinsonian pain is the core feature of the putative Park pain subtype of PD. This study aimed to explore the cognitive and behavioral profile of PD patients with central parkinsonian pain. Material and Methods. A structured interview was used to identify and characterize pain in a cohort of 260 consecutive PD patients. The Ford classification of pain was applied. The Dementia Rating Scale-2 (DRS-2) and the Impulse Control Disorders in Parkinson's Disease Short Form (QUIP-S) were administered, and patients' smoking habits were recorded. The Unified Parkinson's Disease Rating Scale (UPDRS) was used to assess motor and nonmotor symptoms in off and on conditions. RESULTS: One hundred and eighty-eight patients (68%) reported pain; and in 41 (22%) of them, the pain was classified as central parkinsonian pain. PD patients with central parkinsonian pain had better cognitive performance in DRS-2 Initiation/Perseveration and Conceptualization subscales but reported more other compulsive behaviors (e.g., hobbyism, punding, and walkabout) and had more current smoking habits than those without pain or with non-central parkinsonian pain. Multiple logistic regression analyses revealed that the DRS-2 Conceptualization subscale, other compulsive behaviors, and smoking habits remained statistically associated with central parkinsonian pain even when other significant covariates were considered. Only patients with pain, regardless of type, had a gambling disorder. Discussion. The study results provide further evidence that pain revealed that patients with central parkinsonian pain are more likely to present compulsive or addictive behaviors, despite having more preserved cognitive performance. Patients with central parkinsonian pain appear to have a distinct phenotype of PD.

Molecular dynamics simulations reveal disruptive self-assembly in dynamic peptide libraries.

There is significant interest in the use of unmodified self-assembling peptides as building blocks for functional, supramolecular biomaterials. Recently, dynamic peptide libraries (DPLs) have been proposed to select self-assembling materials from dynamically exchanging mixtures of dipeptide inputs in the presence of a nonspecific protease enzyme, where peptide sequences are selected and amplified based on their self-assembling tendencies. It was shown that the results of the DPL of mixed sequences (e.g. starting from a mixture of dileucine, L2, and diphenylalanine, F2) did not give the same outcome as the separate L2 and F2 libraries (which give rise to the formation of F6 and L6), implying that interactions between these sequences could disrupt the self-assembly. In this study, coarse grained molecular dynamics (CG-MD) simulations are used to understand the DPL results for F2, L2 and mixed libraries. CG-MD simulations demonstrate that interactions between precursors can cause the low formation yield of hexapeptides in the mixtures of dipeptides and show that this ability to disrupt is influenced by the concentration of the different species in the DPL. The disrupting self-assembly effect between the species in the DPL is an important effect to take into account in dynamic combinatorial chemistry as it affects the possible discovery of new materials. This work shows that combined computational and experimental screening can be used complementarily and in combination providing a powerful means to discover new supramolecular peptide nanostructures.

Levedura de cana-de-açúcar spray dry na alimentação de suínos na fase de crescimento e terminação / Sugar cane spray dry yeast on growing and finishing pigs feeding

Foi estudado o valor nutricional (digestibilidade total e ileal) de duas leveduras spray dry (cana-de-açúcar - LEV35 e cerveja+cana-de-açúcar - LEV40) e o efeito da sua inclusão em rações para suínos na fase de crescimento e terminação. Os valores de ED (kcal/kg) da LEV35 e da LEV40 foram 3.496 e 3.901 e EM (kcal/kg) foram 3.475 e 3.862, respectivamente. Os valores de lisina, metionina+cistina e treonina digestível para a levedura de cana-de-açúcar e da levedura de cerveja+cana-de-açúcar são 2,66 e 2,64, 1,11 e 1,03, 1,95 e 1,92, respectivamente. No desempenho foram utilizados 40 suínos com peso inicial de 34,39± 7,57kg (crescimento) e de 62,45± 5,68kg (terminação), distribuídos em delineamento inteiramente casualizado com cinco níveis de inclusão (0, 5, 10, 15 e20%) da LEV35. Na fase de crescimento, houve piora do GDP e da CA com o aumento da inclusão. Na fase de terminação, porém, houve efeito quadrático para o CDR, sendo o melhor nível 3.32%. Da mesma forma, ocorreu piora linear para o GDP, CA, peso de carcaça quente, rendimento de carcaça fria e peso de pernil. Os resultados sugerem que a adição de níveis crescentes da LEV35 pode prejudicar o desempenho dos suínos.

The nutritional value of two spray dry yeast (sugar cane - SCYSD and brewer+sugar cane - BYSD) and their inclusion effects on growing and finishing pigs feeding was studied. The DE (kcal/kg) values for SCYSD and BYSD were 3.496 and 3.901 and for ME (kcal/kg) they were 3.475 and 3.862. The values of digestible lysine, methionine+cistine and threonine for SCYSD and BYSD were: 2.66 and 2.64%; 1.11 and 1.03%: 1.95 and 1.92%. 40 pigs with initial weight of 34.39±7.57kg (growing) and 62.45±5.68kg (finishing), allotted in a completely randomized design with five levels of SCYSD inclusion were used in the performance assay. In the growing phase, there was an impairing on DWG and F:G, however, in the finishing phase, DFI presented a quadratic effect, being 3.32% the best level and linear reduction of DWG, F:G, slaughter weight, hot carcass weight, cold carcass yield and ham weight. The results suggest that increasing levels of SCYSD may impair the performance of growing and finishing pigs.

Linalool and methyl chavicol present basil (Ocimum sp. ) cultivated in Brazil / Linalol e metil-chavicol presentes em manjericão (Ocimum sp. ) cultivados no Brasil

In Brazil, Ocimum species are commonly known as aromatic and restorative herbs. The present research aimed to study the chemical composition of the essential oils of fresh and dry basil (Ocimum sp) leaves obtained by hydrodistillation and analyzed by GC-FID and GC-MS. The obtained yield was 0.70% for dry leaves and 0.26% for fresh leaves. The major compounds were: linalool (29.50-32.26%) and methyl chavicol (36.81-41.62%). Eucalyptol could also be detected (9.99-7.68%). The oil from dry leaves presented a more complex chemical composition. This study serves to contribute to the knowledge of medicinal plants occurring in Brazil.

No Brasil, as espécies de Ocimum são conhecidas como ervas aromáticas e restaurativas. Nesse trabalho foi estudado a composição química dos óleos essenciais das folhas frescas e secas de manjericão (Ocimum sp) obtido por hidrodestilação e analisados por CG-FID e CG-EM. Os teores encontrados foram de 0,70% para as folhas secas e 0,26% para as folhas frescas. Os componentes majoritários foram: Linalol (29,50-32,26%) e metil-chavicol (36,81-41,62%). Eucaliptol também foi detectado (9,99-7,68%). O óleo das folhas secas apresentou composição química mais complexa. Esse trabalho contribui para o conhecimento das plantas medicinais de ocorrência no Brasil.

Glicerina semipurificada vegetal e mista na alimentação de coelhos em crescimento / Vegetal and mixed semipurified glycerin in the feeding of growing rabbits

Dois experimentos foram conduzidos com o objetivo de determinar a energia digestível da glicerina semipurificada vegetal e mista e o desempenho de coelhos em crescimento alimentados com dietas contendo os coprodutos. No ensaio de digestibilidade, foram utilizados 108 coelhos da raça Nova Zelândia Branco, com 45 dias de idade, distribuídos ao acaso em nove tratamentos (0, 4, 8, 12 e 16% de inclusão de glicerina vegetal e mista na dieta), com 12 repetições. Para o ensaio de desempenho, utilizaram-se 180 coelhos da raça Nova Zelândia Branco, dos 32 aos 70 dias de idade, distribuídos ao acaso em arranjo fatorial 2 x 4 (dois tipos de glicerina e quatro porcentagens de inclusão: 3, 6, 9 e 12%) mais uma dieta referência, com 10 repetições e dois animais por unidade experimental. Glicerinas vegetal e mista apresentaram energia digestível de 4.048 e 3.697kcal/kg MS, respectivamente. Entre 32 e 50 dias de idade dos coelhos, a dieta com 12% de glicerina mista prejudicou (P<0,05) o ganho de peso (32,14 g/dia), a conversão alimentar (3,57) e o custo por quilo de ganho de peso (R$ 2,08) em relação à dieta referência (39,42g/dia, 2,87 e R$1,69, respectivamente). Dos 32 aos 70 dias, o ganho de peso (30,11g/dia) e a conversão alimentar (3,99) dos animais que receberam 12% de glicerina mista na dieta foram piores (P<0,05) em relação aos da dieta referência (34,00g/dia e 3,65, respectivamente). Para as características de desempenho, dos 32 aos 70 dias, não foram verificadas diferenças (P>0,05) entre a inclusão de glicerina vegetal na dieta e a dieta referência, porém a maior viabilidade econômica (P<0,05) foi com 12% de inclusão (R$1,89 x R$2,15, respectivamente). A glicerina vegetal pode ser incluída em até 12% da dieta e a mista, em até 9%, diminuindo o custo de produção sem afetar o desempenho animal.

Two trials were conducted with the goal of determining the digestible energy of vegetal and mixed semi purified glycerin and the performance of growing rabbits fed with diets containing the byproducts. In the digestibility assay 108 New Zealand White rabbits, 45 days old, were used, assigned in a completely randomized design into nine treatments (0, 4, 8, 12 and 16% of glycerins inclusion), with 12 replications. The treatment with 0% of glycerin inclusion was considered the reference diet. In the performance assay, 180 New Zealand White rabbits, 32 to 70 days of age, were assigned to a completely randomized design into a 2 × 4 factorial arrangement (two types of glycerin and four percentages of inclusion: 3, 6, 9 and 12%) plus a reference diet and ten replications with two animals per experimental unit. Vegetal and mixed glycerin showed a digestible energy of 4,048 and 3,697 kcal/kg of dry matter, respectively. From 32 to 50 days of age, the diet with 12% of mixed glycerin affected (P<0.05) weight gain (32.14g/day), feed conversion (3.57) and cost per kilo of weight gain (R$2.08) in relation to the reference diet (39.42g/day, 2.87 and R$ 1.69, respectively). From 32 to 70 days, weight gain (30.11g/day) and feed conversion (3.99) of the animals fed with the diet containing 12% of mixed glycerin were worst (P<0.05) in relation to the reference diet (34.00 g/day and 3.65, respectively). Regarding characteristics of animal performance, from 32 to 70 days, no differences (P>0.05) were observed between the inclusion of vegetal glycerin in the diet and the reference diet, but better economic viability was verified (P<0.05) with the diet containing 12% of vegetal glycerin (R$1.89 x R$2.15, respectively). Vegetal glycerin can be included up to 12% in the diet and mixed up to 9%, reducing production cost without affecting animal performance.

Method of using increasing levels of substitution of the basal diet by test feedstuffs in pig digestibility trials / Metodologia de uso de níveis crescentes de substituição da ração referência pelo alimento teste em ensaios de digestibilidade com suínos

Two experiments were carried out to study the methodology of using increasing levels of substitution of the basal diet with fibrous test feedstuffs (sticky coffee hull - SCH) in digestibility trials with pigs. In Experiment 1, a digestibility trial was conducted using 30 crossbred barrows, allotted in a randomized block design. In Experiment 2, 42 growing and 42 finishing pigs were used, allotted in a completely randomized design, with six diets and seven replicates, with one animal per experimental unit. The six diets consisted of: a control diet, four diets using SCH ME values as obtained in Experiment 1 plus a diet using SCH ME value estimated by linear regression equation for 15% substitution. The digestibility study indicated that the use of increasing levels of substitution (7, 14, 21 and 28%) reduced SCH digestibility. ME values, as-fed basis, were 2,456, 2,377, 2,247 and 1,945kcal/kg. The overall results indicate that higher levels of substitution overestimate the energy value and that the method of increasing levels of substitution of the basal diet with feedstuffs test can be used to more accurately estimate the energy values of fibrous feedstuffs for pigs. For growing and finishing pigs respectively, up to 28% and 15% of sticky coffee hull can be used without impairing pig performance and economic feasibility.

Dois experimentos foram realizados para se estudar a metodologia de uso de porcentagens crescentes de substituição da ração referência pelo alimento teste fibroso (casca de café melosa - CCM), em ensaios de digestibilidade com suínos. No Experimento I, foi realizado um ensaio de digestibilidade utilizando 30 machos castrados, distribuídos em delineamento de blocos ao acaso. No Experimento II, foram utilizados 42 suínos na fase de crescimento e 42 suínos na fase de terminação, distribuídos em delineamento inteiramente ao acaso, com seis rações, sete repetições e um animal por unidade experimental. As seis rações foram: uma ração controle, quatro rações usando os valores de energia metabolizável (EM) da CCM obtidos no Experimento I e uma ração com EM da CCM estimada por equação de regressão linear para 15% de substituição. Os estudos de digestibilidade indicaram que o uso de porcentagens crescentes de substituição - 7, 14, 21 e 28% - reduziu a digestibilidade da CCM. Os valores de EM, na matéria natural, obtidos para a CCM foram 2.456, 2.377, 2.247 e 1.945kcal/kg. Os resultados indicam que porcentagens mais elevadas de substituição superestimam o valor energético e que a crescente substituição da ração referência pelo alimento teste pode ser utilizada para estimar, de forma mais precisa, os valores energéticos de alimentos fibrosos para suínos. Para suínos em crescimento e em terminação, pode-se usar, respectivamente, até 28% e 15% de casca de café melosa sem prejudicar o desempenho e a viabilidade econômica.

Avaliação nutricional de soja integral desativada e desempenho de leitões na fase de creche / Nutritional evaluation of disabled whole soybean and performance of piglets on nurse phase

Dois experimentos foram realizados para determinar o valor nutricional e verificar o desempenho de leitões dos 6 aos 15kg, alimentados com dietas que continham dois tipos de soja integral desativada, caracterizada pela presença (SC) ou não de casca (SS). No ensaio de digestibilidade total, foram utilizados 15 leitões machos, castrados, com média de peso inicial de 7,36±1,71kg, alojados em gaiolas de metabolismo. Exceto para energia bruta (EB), não foram observadas diferenças entre tratamentos nos coeficientes de digestibilidade da matéria seca, da proteína bruta, do extrato etéreo e da matéria orgânica, e no coeficiente de metabolização da EB entre as duas sojas avaliadas. Os teores de energia digestível e energia metabolizável na matéria natural para SC e SS foram: 3.979 e 4.300kcal/kg; 3.768 e 4.111kcal/kg, respectivamente. No experimento de desempenho, foram utilizados 56 leitões, desmamados aos 21 dias de idade, com média de peso inicial de 6,19±0,67kg. Neste experimento, os leitões receberam os dois tipos de soja integral desativada em três porcentagens de inclusão. Não foram observadas diferenças para as variáveis de desempenho com a inclusão da soja desativada às dietas. Concluiu-se que os tipos e as porcentagens de inclusão da soja podem ser utilizados na dieta de leitões.

Two experiments were carried out to determine the nutritional value and to verify the piglets performance from 6 to 15kg, fed diets with two types of disabled whole soybeans characterized by shell presence (CS) or not (SS). In the digestibility assay 15 castrated male piglets were used, with average weight of 7.36±1.71kg, housed in metabolism cages. Except for gross energy (EB), no differences between treatments were observed for the dry matter digestibility, crude protein, ether extract and organic matter, and for the coefficient of metabolism of EB between the two soybeans evaluated. The values of digestible energy (DE), as well the metabolizable energy (ME) on fed basis for SC and SS were: 3,979 and 4,300kcal/kg, 3,768 and 4,111kcal/kg, respectively. In the performance experiment 56 weaned piglets were used, at 21 days of age with initial body weight of 6.19±0.67kg. No differences were observed in the performance variables with the inclusion of SS and SC disabled soybeans in the diets, concluding that the studied soybeans can be used for piglet diets.

Peroral esophageal segmentectomy and anastomosis with single transthoracic trocar: a step forward in thoracic NOTES.

BACKGROUND AND STUDY AIMS: A transesophageal natural orifice transluminal endoscopic surgery (NOTES) approach has been proposed for thoracic and mediastinal access. Similarly to transgastric surgery, serious limitations remain related to creating an esophagotomy and its safe closure. A hybrid approach in thoracic NOTES could work as an intermediate step before pure transesophageal NOTES. We assessed the benefit of hybrid thoracic NOTES for peroral segmental esophagectomy and subsequent complete esophageal anastomosis with a single transthoracic port. METHODS: Two protocols were used to attempt esophago-esophageal anastomosis: ex vivo using a phantom model (n = 5), and in vivo after esophageal mobilization, and segmental esophagectomy achieved using either a gastroscope (flexible) (n = 5) or thoracoscope (rigid) instruments (n = 5). A forward-viewing double-channel endoscope and a transthoracic operative thoracoscope with a working channel were coordinated in order to create a complete single-layer, end-to-end esophageal anastomosis ex vivo as well as in vivo. Feasibility and anastomosis quality were evaluated by inside and outside assessment of: patency, the incorporation of mucosa in all stitches, and a leak test. RESULTS: Anastomosis was achieved in all ex vivo experiments and thoracoscopically-led in vivo procedures. All anastomoses were patent, allowing distal passage of the endoscope, with mucosa incorporation. In in vivo experiments, a leak was detected in three animals and corrected with additional stitching. CONCLUSIONS: Peroral esophageal anastomosis with a single transthoracic trocar is feasible, which may represent a step forward in thoracic NOTES.

Relações treonina: lisina digestíveis para suínos na fase inicial, alimentados com rações de baixa proteína, calculadas de acordo com o conceito de energia líquida / Digestible threonine: lysine ratios for starting pigs fed low protein diets, considering net energy concept

Foram realizados dois experimentos com o objetivo de estudar, no primeiro, o efeito de diferentes relações treonina:lisina digestíveis (TL) sobre a utilização do nitrogênio (N) em suínos na fase inicial, dos 15 aos 30kg de peso, e, no segundo, o efeito dessas relações sobre o desempenho dos animais. No primeiro experimento, foi avaliado o balanço de nitrogênio, utilizando-se 20 suínos machos castrados, híbridos comerciais de média a alta deposição de tecido magro, com peso inicial de 23,0±4,1kg. Os suínos foram distribuídos em um delineamento experimental inteiramente ao acaso. As rações continham baixo nível de proteína (17,3 por cento), e as relações TL foram: 0,574; 0,624; 0,673; 0,722 e 0,772. A proteína bruta total excretada (PBTE), a proteína bruta retida (PBR) e a utilização líquida da proteína (ULP) apresentaram efeito quadrático, e os melhores valores nas relações foram 0,648; 0,648 e 0,649, respectivamente. A melhor relação TL foi 0,649 (média da PBR e ULP). No segundo experimento, foi avaliado o efeito dessa relação sobre o desempenho dos suínos na fase inicial. Foram utilizados 60 animais (30 machos castrados e 30 fêmeas) com peso inicial de 15,5±1,5kg, de características semelhantes ao primeiro experimento, distribuídos em um delineamento experimental inteiramente ao acaso, em esquema fatorial 5x2 (cinco relações TL e dois sexos, com dois animais por baia). Foram utilizadas seis baias por tratamento, com três de machos e três de fêmeas cada. Não houve efeito da relação TL sobre o consumo diário de ração e o ganho diário de peso, e houve efeito quadrático, com ponto de mínimo, sobre a conversão alimentar com a relação TL de 0,691. Os resultados indicam que a relação TL de 0,649 maximiza a retenção de nitrogênio e a relação TL de 0,691 permite melhor conversão alimentar para leitões dos 15 aos 30kg de peso.

Two experiments were carried out to evaluate the effect of digestible threonine:lysine ratio (TL) on nitrogen (N) use and on growth performance of starting pigs (15-30kg). Experiment I evaluated nitrogen balance using twenty high-lean commercial crossbred barrows, with initial weight of 23.0±4.1kg. Pigs were allotted in a randomized design. Diets were formulated with low crude protein levels (17.3 percent) and TL ratios were: 0.574; 0.624; 0.673; 0.722; and 0.772. Excreted crude protein (CPEX), crude protein retention (CPR), and net protein utilization (NPU) showed quadratic effect and the best TL ratio values were achieved at 0.648, 0.648, and 0.649, respectively. The best TL ratio was 0.649 (CPR and NPU means). Experiment II was carried out to examine the same TL ratio effects on the performance of pigs. Sixty pigs (30 barrows and 30 gilts), averaging 15.5±1.5kg, used in experiment II, were allotted in a randomized design, following a factorial scheme (5x2), being five TL ratios (same as in experiment I) and two genders. Six pens per treatment (three barrows and three gilts) were used. There was no effect of TL ratio on daily feed intake and on average weight gain. However, the feed:gain ratio showed a quadratic effect and the best TL ratio was achieved at 0.691. The results pointed out that the 0.649 TL ratio maximized nitrogen retention and the 0.694 TL ratio allowed a better feed conversion for starting pigs averaging 15 to 30kg of b.w.

An electronic pressure-meter nociception paw test for mice.

The aim of the present investigation was to describe and validate an electronic mechanical test for quantification of the intensity of inflammatory nociception in mice. The electronic pressure-meter test consists of inducing the animal hindpaw flexion reflex by poking the plantar region with a polypropylene pipette tip adapted to a hand-held force transducer. This method was compared to the classical von Frey filaments test in which pressure intensity is automatically recorded after the nociceptive hindpaw flexion reflex. The electronic pressure-meter and the von Frey filaments were used to detect time versus treatment interactions of carrageenin-induced hypernociception. In two separate experiments, the electronic pressure-meter was more sensitive than the von Frey filaments for the detection of the increase in nociception (hypernociception) induced by small doses of carrageenin (30 microg). The electronic pressure-meter detected the antinociceptive effect of non-steroidal drugs in a dose-dependent manner. Indomethacin administered intraperitoneally (1.8-15 mg/kg) or intraplantarly (30-300 microg/paw) prevented the hypersensitive effect of carrageenin (100 microg/paw). The electronic pressure-meter also detected the hypernociceptive effect of prostaglandin E2 (PGE2; 10-100 ng) in a dose-dependent manner. The hypernociceptive effect of PGE2 (100 ng) was blocked by dipyrone (160 and 320 microg/paw) but not by intraplantar administration of indomethacin (300 microg/paw). The present results validate the use of the electronic pressure-meter as more sensitive than the von Frey filaments in mice. Furthermore, it is an objective and quantitative nociceptive test for the evaluation of the peripheral antinociceptive effect of anti-inflammatory analgesic drugs, which inhibit prostaglandin synthesis (indomethacin) or directly block the ongoing hypernociception (dipyrone).

An electronic pressure-meter nociception paw test for mice

The aim of the present investigation was to describe and validate an electronic mechanical test for quantification of the intensity of inflammatory nociception in mice. The electronic pressure-meter test consists of inducing the animal hindpaw flexion reflex by poking the plantar region with a polypropylene pipette tip adapted to a hand-held force transducer. This method was compared to the classical von Frey filaments test in which pressure intensity is automatically recorded after the nociceptive hindpaw flexion reflex. The electronic pressure-meter and the von Frey filaments were used to detect time versus treatment interactions of carrageenin-induced hypernociception. In two separate experiments, the electronic pressure-meter was more sensitive than the von Frey filaments for the detection of the increase in nociception (hypernociception) induced by small doses of carrageenin (30 µg). The electronic pressure-meter detected the antinociceptive effect of non-steroidal drugs in a dose-dependent manner. Indomethacin administered intraperitoneally (1.8-15 mg/kg) or intraplantarly (30-300 µg/paw) prevented the hypersensitive effect of carrageenin (100 µg/paw). The electronic pressure-meter also detected the hypernociceptive effect of prostaglandin E2 (PGE2; 10-100 ng) in a dose-dependent manner. The hypernociceptive effect of PGE2 (100 ng) was blocked by dipyrone (160 and 320 µg/paw) but not by intraplantar administration of indomethacin (300 µg/paw). The present results validate the use of the electronic pressure-meter as more sensitive than the von Frey filaments in mice. Furthermore, it is an objective and quantitative nociceptive test for the evaluation of the peripheral antinociceptive effect of anti-inflammatory analgesic drugs, which inhibit prostaglandin synthesis (indomethacin) or directly block the ongoing hypernociception (dipyrone).

DNA topoisomerase inhibitors: biflavonoids from Ouratea species.

Topoisomerase inhibitors are agents with anticancer activity. 7"-O-Methyl-agathisflavone (I) and amentoflavone (II) are biflavonoids and were isolated from the Brazilian plants Ouratea hexasperma and O. semiserrata, respectively. These biflavonoids and the acetyl derivative of II (IIa) are inhibitors of human DNA topoisomerases I at 200 microM, as demonstrated by the relaxation assay of supercoiled DNA, and only agathisflavone (I) at 200 microM also inhibited DNA topoisomerases II-alpha, as observed by decatenation and relaxation assays. The biflavonoids showed concentration-dependent growth inhibitory activities on Ehrlich carcinoma cells in 45-h culture, assayed by a tetrazolium method, with IC50 = 24 +/- 1.4 microM for I, 26 +/- 1.1 microM for II and 10 +/- 0.7 microM for IIa. These biflavonoids were assayed against human K562 leukemia cells in 45-h culture, but only I showed 42% growth inhibitory activity at 90 microM. Our results suggest that biflavonoids are targets for DNA topoisomerases and their cytotoxicity is dependent on tumor cell type.

DNA topoisomerase inhibitors: biflavonoids from Ouratea species

Topoisomerase inhibitors are agents with anticancer activity. 7"-O-Methyl-agathisflavone (I) and amentoflavone (II) are biflavonoids and were isolated from the Brazilian plants Ouratea hexasperma and O. semiserrata, respectively. These biflavonoids and the acetyl derivative of II (IIa) are inhibitors of human DNA topoisomerases I at 200 æM, as demonstrated by the relaxation assay of supercoiled DNA, and only agathisflavone (I) at 200 æM also inhibited DNA topoisomerases II-alpha, as observed by decatenation and relaxation assays. The biflavonoids showed concentration-dependent growth inhibitory activities on Ehrlich carcinoma cells in 45-h culture, assayed by a tetrazolium method, with IC50 = 24 ± 1.4 æM for I, 26 ± 1.1 æM for II and 10 ± 0.7 æM for IIa. These biflavonoids were assayed against human K562 leukemia cells in 45-h culture, but only I showed 42 percent growth inhibitory activity at 90 æM. Our results suggest that biflavonoids are targets for DNA topoisomerases and their cytotoxicity is dependent on tumor cell type

[3 cases of vulvar epidermal cysts after female genital mutilation]. / Trois cas de kystes épidermiques de la vulve après mutilations génitales féminines.

We report three cases of tumors of the vulva following an excision during childhood, in patients aged 22 to 25. The achieved surgical removal gave correct aesthetic and functional results. Histological examination of these tumors revealed epidermal cyst containing keratin. Because of clinical, psychological and social impact of female excision, steps should be taken against such traditional practices.

Heterogeneity of VH-JH gene rearrangement patterns: an insight into the biology of B cell precursor ALL.

Oligoclonal B cell proliferation, as defined by the presence of more than one leukemic clone, has been detected in approximately 20% to 30% of patients with acute lymphoblastic leukemia (ALL) using PCR or Southern blotting. An accurate assessment of these populations is required to avoid false negative measurements of minimal residual disease (MRD) in follow-up bone marrow (BM) samples of ALL patients. In this study, we analysed 29 ALL patients with two or more immunoglobulin heavy (IGH) chain gene rearrangements in the presentation samples using IGH fingerprinting PCR and sequence analysis. Thirty-nine (51%) of 76 sequences (from 15 patients), shared no VNDNJ homology (ie different CDR3 regions). In the remaining 14 patients, at least two related VH sequences were identified in each patient (identical DNJ sequences). Numerical abnormalities of chromosome 14 was detected in 10 patients. Eight patients were analysed at presentation and relapse. In four of them, expansion of a minor presentation-clone was detected at relapse while the major presentation clone disappeared, confirming 'subclonal evolution'. Finally, in our cohort of patients, the presence of related or unrelated IGH clones did not influence overall survival.

Sodium and chloride requirements of young broiler chickens fed corn-soybean diets (one to twenty-one days of age).

Sodium (Na+) and chloride (Cl-) nutritional requirements, dietary electrolyte balance (DEB), and their effects on acid-base balance, litter moisture, and tibial dyschondroplasia (TD) incidence for young broiler chickens were evaluated in two trials. One-day-old Cobb broilers were distributed in a completely randomized design with six treatments, five replicates, and 50 birds per experimental unit. Treatments used in both experiments were a basal diet with 0.10% Na+ (Experiment 1) or Cl- (Experiment 2) supplemented to result in diets with Na+ or Cl- levels of 0.10, 0.15, 0.20, 0.25, 0.30, or 0.35%, respectively. In Experiment 1, results indicated an optimum Na+ requirement of 0.26%. Sodium levels caused a linear increase in arterial blood gas parameters, indicating an alkalogenic effect of Na+. The hypertrophic area of growth plate in the proximal tibiotarsi decreased with Na+ levels. The TD incidence decreased with increases in dietary Na+. Litter moisture increased linearly with sodium levels. In Experiment 2, the Cl- requirement was estimated as 0.25%. Chloride levels caused a quadratic effect (P < or = 0.01) on blood gas parameters, with an estimated equilibrium [blood base excess (BE) = 0] at 0.30% of dietary Cl-. No Cl- treatment effects (P > or = 0.05) were observed on litter moisture or TD incidence. The best DEB for maximum performance was 298 to 315 mEq/kg in Experiment 1 and 246 to 264 mEq/kg in Experiment 2. We concluded that the Na+ and Cl- requirements for optimum performance of young broiler chickens were 0.28 and 0.25%, respectively.

Immunoglobulin heavy-chain gene rearrangement in adult acute lymphoblastic leukemia reveals preferential usage of J(H)-proximal variable gene segments.

The aim of this study was to characterize individual-segment and overall patterns of V(H) gene usage in adult B-lineage acute lymphoblastic leukemia (ALL). Theoretical values of V(H) segment usage were calculated with the assumption that all V(H) segments capable of undergoing rearrangement have an equal probability of selection for recombination. Leukemic clones from 127 patients with adult B-lineage acute leukemias were studied by fingerprinting by means of primers for the framework 1 and joining segments. Clones from early preimmune B cells (245 alleles identified) show a predominance of V(H)6 family rearrangements and, consequently, do not conform to this hypothesis. However, profiles of V(H) gene family usage in mature B cells, as investigated in peripheral blood (6 samples), B-cell lymphomas (36 clones) and chronic lymphocytic leukemia (56 clones), are in agreement with this theoretical profile. Sequence analyses of 64 V(H) clones in adult ALL revealed that the rate of V(H) usage is proportional to the proximity of the V(H) gene to the J(H) locus and that the relationship can be mathematically defined. Except for V(H)6, no other V(H) gene is excessively used in adult ALL. V(H) pseudogenes are rarely used (n = 2), which implies the existence of early mechanisms in the pathway to B-cell maturation to reduce wasteful V(H)-(D(H))-J(H) recombination. Finally, similar to early immunoglobulin-H rearrangement patterns in the mouse, B cells of ALL derive from a pool of cells more immature than the cells in chronic lymphoid B-cell malignancies.

Human T cell leukemia virus type 1 (HTLV-1) antibodies in healthy populations and renal transplanted patients in the north-east of Brazil.

The seroprevalence of human T cell leukemia virus type 1 (HTLV-1) infection was investigated in Brazilians (570): native inhabitants (298) and descendants from Japanese (272) living in Recife and its neighborhoods--North-east of Brazil. Furthermore, polytransfused renal transplanted patients (54) were also examined for the serological status to this virus. The seropositivity to HTLV-1, screened by enzyme-linked immunosorbent assay (ELISA), was low: 1.34% for the local population and 0.73% for the descendants from Japanese. However, the seropositivity for the renal transplanted patients was found to be 11.1%. This higher value suggests that this retrovirus infection seems to be of importance in this clinical condition.