Thermoregulatory profile of neurodegeneration-induced dementia of the Alzheimer's type using intracerebroventricular streptozotocin in rats.

AIM: Here, we have extensively investigated the relationship between thermoregulation and neurodegeneration-induced dementia of the Alzheimer's type using intracerebroventricular injections of streptozotocin (icv-STZ). METHODS: Male Wistar rats were treated with bilateral injections of icv-STZ, and their thermoregulatory profiles (core body temperature, tail-skin temperature, cold and heat defence responses and thermal place preference) were evaluated. Spatial memory, locomotor activity, social interaction, brain ventricular volume, and Aß1-42 and tau protein levels in the brain were analysed to characterize the effects of STZ on the brain and behaviour. RESULTS: In addition to deficits in spatial memory, reduced social interaction and an increased brain ventricular volume, icv-STZ rats presented a pattern of hyperthermia, as demonstrated by an increased core body temperature. Hyperthermia was due to the activation of both autonomic heat conservation and behavioural cold avoidance, as STZ-treated rats presented tail-cutaneous vasoconstriction and an altered thermal preference. They also showed a distinct cold defence response when exposed to cold. CONCLUSION: Our data bring evidence that icv-STZ in rats causes hyperthermia, with activation of both autonomic and behavioural thermoregulatory defence responses when challenged at colder temperatures, leading us to hypothesize that they are more efficient in preventing hypothermia. These data are relevant for a better understanding of neurodegenerative disease mechanisms.

Desempenho de tambaquis (Colossoma macropomum) submetidos a restrição alimentar e a realimentação em tanques-rede / Performance of tambaqui submitted feed deprivation and refeeding in cages

Objetivou-se avaliar o desempenho de tambaquis (Colossoma macropomum) submetidos à restrição alimentar e à realimentação em tanques-rede. Durante 60 dias, foram alocados 100 tambaquis (peso inicial de 8,0 ± 0,5g), em 20 tanques-rede. Foram realizados quatro tratamentos: T1=animais alimentados diariamente (controle), T2=alimentados durante seis dias com um dia de restrição de ração (6A/1R), T3=alimentados durante cinco dias com dois dias de restrição (5A/2R) e T4 = alimentados durante quatro dias com três dias de restrição (4A/3R). Os animais foram alimentados duas vezes ao dia, às oito e às 16 horas, até a aparente saciedade, com ração extrusada comercial (42%PB). Utilizaram-se cinco repetições para cada tratamento e cinco peixes por unidade experimental, em um delineamento inteiramente ao acaso. A coleta de dados para avaliação do desempenho produtivo foi feita com base no peso final, no ganho de peso, no consumo médio de ração, na conversão alimentar, no comprimento total, no comprimento padrão, na altura, no índice de cabeça e de perfil, na taxa de eficiência proteica, na taxa de crescimento específico e na sobrevivência. Os resultados foram submetidos à ANOVA e ao teste de Tukey (P≥5). O tratamento 5A/2R apresentou-se como a melhor ferramenta na redução de custos de produção sem prejuízo ao desempenho produtivo de juvenis de tambaqui.

The aim of this research was to evaluate the performance of tambaqui juveniles (Colossoma macropomum) submitted to feed deprivation and refeeding in cages. For 60 days of experimentation, 100 tambaquis were used (initial weight 8.0 ± 0.5g), distributed in 20 cages. The treatments were: T1=daily fed animals (control), T2=fed for six days and one day of restriction (6F/1R), T3=fed for five days and two days of restriction (5F/2R) and T4=fed for four days with three days of restriction (4F/3R). With five replicates each, and five fish for each experimental unit, arranged in a completely randomized design. In accordance with treatments, the fishes were fed twice a day at 08:00am and 4:00pm. The data collection for the performance evaluation was based on final weight, weight gain, average feed intake, alimentary conversion, total length, standard length, height, index head, index profile, protein efficiency rate, specific growth rate and survival at the end of the experimental period. Results were submitted to ANOVA and Tukey test (P≥5). Treatment 5F/2R resulted in the best performance results, which is a tool in reducing production costs without loss in performance of tambaqui juvenile.

Avaliação da imobilidade tônica em codornas de corte via análise de sobrevivência' / Tonic immobility evaluation in meat quail via survival analysis

Tonic immobility (TI) is a way to measure fear, as characterized by the reduced capacity to respond to external stimuli. The time spent in TI indicates the level of fear. Since TI is measured as the time until event occurrence, survival analysis stands out as a suitable statistical method to treat these data. We aimed to investigate the influence of possible factors (lines, sex and age) on fear behavior in meat quail (Coturnix coturnix) measured through TI by using survival analysis (non parametric Kaplan-Meyer method via logrank test). The dataset was composed by TI information provided by 50 animals from each line (UFV1 and UFV2) in each age (14 and 28 days of age), totalizing 200 records. Despite the slight difference between the two evaluated ages, there was no significance for this factor between each studied line, UFV1 (P= 0.1493) and UFV2 (P= 0.2583). The logrank test indicated significant difference (P= 0.0407) between levels of line/sex groups at 14 days of age. We noted that males from UFV2 line presented higher fear behavior in relation to males from UFV1 line. No significant differences were observed for this factor when considering 28 days of age.(AU)

Multiple-trait genomewide mapping and gene network analysis for scrotal circumference growth curves in Brahman cattle.

Fertility traits are economically important in cattle breeding programs. Scrotal circumference (SC) measures are repeatable, easily obtained, highly heritable, and positively correlated with female fertility traits and sperm quality traits in males. A useful approach to summarize SC measures over time is using nonlinear models, which summarize specific measures of SC in a few parameters with biological interpretation. This approach facilitates the selection of bulls with larger SC and maturity index (K), that is, early maturing animals. Because SC is a sex-limited trait, identifying the underlying genomics of growth curve parameters will allow selection across both males and females. We reported the first multitrait genomewide association study (GWAS) of estimated growth curve parameters for SC data in Brahman cattle. Five widely used nonlinear models were tested to fit a total of 3,612 SC records, measured at 6, 12, 18, and 24 mo of age. The von Bertalanffy model, individually fitted for each animal, best fit this SC data. Parameter estimates SC at maturity (A) and K as well as SC at all ages were jointly analyzed in a GWAS to identify 1-Mb regions most strongly associated with each trait. Heritabilities were 0.25 for K and 0.32 for A and ranged from 0.51 to 0.72 for SC at 6 (SC6), 12 (SC12), 18 (SC18), and 24 mo of age (SC24). An overlapping window on chromosome 14 explaining around 0.8% of genetic variance for K, SC12, SC18, and SC24 was observed. The major positional candidate genes within 1 Mb upstream and downstream of this overlapping window were , , , and . Windows of 1 Mb explaining more than 0.4% of each trait on chromosomes 1, 3, 6, 7, 14, 17, 18, 24, 25, and 26 were identified. Pathways and net-work analyses were indicated through transcription factors playing a role on fertility traits: , , , , , , and . Further validation studies on larger populations or other breeds are required to validate these findings and to improve our understanding of the biology and complex genetic architecture of traits associated with scrotal growth and male fertility in cattle.

Peripheral and central antinociceptive effects of the butanolic fraction of Byrsonima verbascifolia leaves on nociception-induced models in mice.

Byrsonima verbascifolia (Malpighiaceae), commonly known as 'murici', is used in folk medicine, for example, in the treatment of inflammation. The anti-inflammatory activity of the butanolic fraction of B. verbascifolia leaves (BvBF) was previously reported by our group, and the present study was designed to evaluate their antinociceptive effects. BvBF (25, 50, and 100 mg/kg) administered intraperitoneally (i.p.) inhibited acetic acid induced abdominal writhing. In the formalin test, BvBF (10, 30 and 100 mg/kg, i.p.) caused a reduction in licking time in both the neurogenic and inflammatory phases. Moreover, we demonstrated that BvBF (30 and 100 mg/kg, i.p.) caused an increase in the latency to response in the hot-plate test. These results demonstrate that BvBF possesses marked peripheral and central antinociceptive activities. Pre-treatment with the non-selective receptor antagonist naloxone (5 mg/kg, i.p.) abolished the antinociceptive effects of BvBF (100 mg/kg, i.p.) in the neurogenic phase of the formalin and hot-plate tests. The anti-inflammatory activity of BvBF (previously reported) as well as the participation of the opioidergic system seems to be responsible, at least in part, for these antinociceptive effects. Finally, BvBF at the doses investigated (25, 50 and 100 mg/Kg) did not cause any toxicity signals, showing that the antinociceptive activity is devoid of sedative and hypomotility effects.

In vitro and in vivo action of Piptadenia viridiflora (Kunth) Benth against Haemonchus contortus in sheep.

Anthelminthic resistant populations of Haemonchus contortus are a major problem in sheep rearing, but plant extracts may offer viable alternative treatments. In our preliminary studies, Piptadenia viridiflora was frequently selected by sheep grazing in the Cerrado. The present research evaluated its in vitro and in vivo anthelmintic activity. The HPLC chromatograms of P. viridiflora aqueous extract (AE) and ethanolic extract (EE) showed the presence of flavonoids. The total condensed tannin (proanthocyanidin) was 0.2 and 1.01% in AE and EE, respectively. In an egg hatching inhibition (EHI) test, the LC90 of AE was 2.4mg/mL, and, of EE, was 2.1mg/mL. After tannin extraction, higher EHI and lower LC90 were observed. In a larval development inhibition test, the LC90 of AE was 13.66mg/g of fecal culture. The highest dose of AE administered to mice (203.0mg/kg bw) was well tolerated, suggesting low toxicity. In vivo, AE was orally administered to lambs at 283mg/kg bw, and, at weeks one, two, and three post-treatment, the mean fecal egg count (FEC) was significantly lower than in untreated lambs (P<0.05). Blood parameters were normal and similar in untreated and treated sheep. For all lamb groups, the mean total serum protein was significantly higher at week two post-treatment than at other evaluated periods (P<0.05). Piptadenia viridiflora extracts had low condensed tannin content and exhibited high anthelminthic efficacy in vitro and significantly reduced FEC. Tannins were not shown to be the principal components affecting EHI, hence it is necessary to isolate and characterize the principal active P. viridiflora compounds, and to assess their possible synergism.

Compostos químicos e aspectos botânicos, etnobotânicos e farmacológicos da Byrsonima verbascifolia Rich ex. A. Juss / Chemical compounds and botanical, ethnobotanical and pharmacological aspects of Byrsonima verbascifolia Rich ex. A. Juss

RESUMO Byrsonima verbascifolia Rich ex. A. Juss é uma espécie do cerrado brasileiro com uso etnobotânico vasto. O objetivo desse trabalho foi realizar um levantamento bibliográfico de artigos originais e revisões, indexados até agosto de 2014 nas bases de dados Periódicos CAPES, Scielo, Scopus, Web of Science e Medline, nos idiomas português e inglês, utilizando a palavra-chave Byrsonima verbascifolia. Foram contemplados a composição química e os aspectos botânicos, etnobotânicos e farmacológicos. Os estudos presentes na literatura avaliaram as atividades antioxidante, antifúngica, antiviral, antimicrobiana, moluscicida, antimutagênica, mutagênica, teratogênica, imunomodulatória, tóxica e citotóxica de extratos dessa espécie. Apenas um estudo avaliou a atividade da Byrsonima verbascifoliaRich ex. A. Juss in vivo, sendo comprovado que o extrato hidrometanólico das folhas não induz teratogênese, mutagênese ou efeito estimulante ou depressor da resposta imune. Metodologias in vitro predominaram o que demonstra a necessidade de investigação científica empregando testes in vivo para a melhor avaliação das outras atividades biológicas mencionadas.

ABSTRACT Byrsonima verbascifolia is a species of Brazilian cerrado with extensive ethnobotanical application. The aim of this study was to perform a bibliographic description of original papers and reviews indexed until August 2014 in the databases of the CAPES Digital Library, Scielo, Scopus, Web of Science and Medline, written in Portuguese and English, using the keyword Byrsonima verbascifolia. The chemical and botanical compositions and the ethnobotanical and pharmacological aspects were contemplated. The researches in the reports evaluated the antioxidant, antifungal, antiviral, antimicrobial, molluscicide, antimutagenic, mutagenic, teratogenic, immunomodulatory, toxic and cytotoxic activities of the extracts of this specie. Only one study evaluated the in vivo activity of the Byrsonima verbascifolia Rich ex. A. Juss and proved that the hydromethanolic extract from the leaves does not induce teratogenesis, mutagenesis, stimulant or depressant effect of the immune response. The In vitro methodologies represented the higher number of researches demonstrating the need of scientific investigation using in vivo tests for better assessment of other biological activities mentioned.

Desenvolvimento de bezerros leiteiros alimentados com silagem de leite de transição: II - Órgãos internos / Development of dairy calves fed silage transition milk: II - Internal organs

Avaliou-se o tamanho absoluto e relativo dos órgãos internos de bezerros Holandeses aleitados com leite, silagem de leite de transição diluída em água ou misturada em leite. Foram utilizados 18 animais, machos, com 60 dias de idade e peso corporal médio de 70,3kg (±11,8kg). O delineamento experimental foi inteiramente ao acaso, com três tratamentos e seis repetições. Os animais foram abatidos aos dois meses de idade, sendo previamente submetidos a jejum alimentar de 16 horas. O aleitamento modificou os pesos dos órgãos internos e da gordura omental dos animais, exceto para rins e gordura mesentérica, e não alterou o consumo de alimentos sólidos. A silagem de leite de transição diluída em água comprometeu o desempenho dos bezerros, refletindo no peso dos órgãos internos e de gordura omental, e apresentou pesos absolutos para fígado, baço e gordura omental de 1.072, 186 e 133g, respectivamente. A silagem misturada em leite proporcionou resultados mais semelhantes ao fornecimento exclusivo de leite, demonstrando-se como opção para o aleitamento de bovinos jovens...

This study aimed to evaluate the absolute and relative size of internal organs of Holstein calves which suckled milk, silage transition milk diluted with water or mixed in milk. We used 18 male animals, 60 days old with a mean body weight of 70.3kg (± 11.8kg). The experimental design was completely randomized with three treatments and six replications. The animals were slaughtered at two months, and previously fasted for 16 hours. Breast feeding changed the weights of internal organs and omental fat of animals, except for kidney and mesenteric fat, and did not affect food intake solids. The silage transition milk diluted in water compromised the performance of the calves, reflecting on the weight of internal organs and omental fat, and showed absolute weights for liver, spleen and omental fat of 1072, 186 and 133g, respectively. The silage mixed with milk yielded results more similar to the exclusive milk supply, being an option for suckling calves...

Desempenho de tilápias-do-nilo alimentadas com farelo da casca de pequi / Performance of Nile tilapia fed with bran made of pequi peel

Avaliou-se o desempenho de tilápias-do-nilo alimentadas com farelo da casca de pequi (Caryocar brasiliense). Foram utilizados 200 alevinos, com idade de 37 dias e peso corporal médio de 0,63±0,25g, distribuídos em delineamento inteiramente ao acaso, com quatro tratamentos ­ zero, 20, 40 e 60% de substituição de ração comercial por farelo da casca de pequi ­ e cinco repetições representadas por caixas de cloreto de polivinila com capacidade para 130L, contendo 10 peixes cada, totalizando 20 unidades experimentais. As características de desempenho avaliadas foram consumo de ração, peso corporal, ganho de peso, conversão alimentar, comprimento total e viabilidade criatória. A conversão alimentar ­ 1,96µ; 2,21µ; 2,63µ; 3,12µ - piorou linearmente com a inclusão do farelo de casca da pequi, enquanto as demais variáveis de desempenho não foram influenciadas pelos tratamentos. Conclui-se que a inclusão do farelo da casca de pequi na ração piora a conversão alimentar, sem alterar as demais variáveis de desempenho.

The performance of Nile tilapia fed with bran made of pequi peel was evaluated. Two hundred fingerlings, at 37 days of age and with mean body weight of 0.63±0.25 g, were distributed in a completely randomized design with four treatments ­0, 20, 40 and 60% of replacement of commercial diet with bran made of pequi peel ­with five repetitions represented by boxes of polyvinyl chloride (PVC) with capacity for 130 L, with 10 fish each, totalizing 20 experimental units. The performance characteristics evaluated were feed intake, body weight, weight gain, feed conversion, total length, and live viability. Feed conversion ­1.96µ; 2.21µ; 2.63µ; 3.12µ­ increased linearly with the inclusion of bran made of pequi peel, while the other performance variables were not influenced by treatments. The conclusion is that the inclusion of bran peel in the pequi diet worsened feed conversion, without changing other performance variables.

Produção de biomassa de erva-cidreira [Lippia alba (Mill. ) N.E.Br. ] sob adubação com composto de capim elefante inoculado e sem inoculação de actinomicetos / Biomass production of Lippia alba (Mill. ) N.E.Br. under fertilization with compost inoculated elephant grass and without inoculation of actinomycetes

A erva-cidreira [Lippia alba (Mill.) N. E. Br.] é uma espécie da família Verbenaceae amplamente utilizada pela população brasileira, devido às propriedades calmante, espasmolítica suave, analgésica, sedativa, ansiolítica e levemente expectorante. Para implantação do experimento foi produzido composto orgânico de capim elefante + esterco, na proporção de 70% de material vegetal e 30% de esterco, sem inoculação e inoculados com os isolados de actinomicetos do gênero Streptomyces: AC16; AC26; AC92 e AC103. Os compostos foram acondicionados em sacos de polietileno contendo 10,0 kg de solo adicionados na proporção equivalente a 20 t ha-1 e foram reaplicados logo após a primeira colheita. As colheitas da parte aérea foram realizadas aos 75 e 165 dias após o transplante. As raízes foram colhidas logo após a segunda colheita. Os tratatamentos com adubação orgânica promoveram aumento médio na produção de biomassa da erva-cidreira de 184, 83, 125, 115 e 122% para biomassa seca da parte aérea (MSPA) na primeira colheita, de MSPA na segunda colheita, biomassa seca total da parte aérea (MSTPA), biomassa seca de raiz (MSR) e biomassa seca total da cultura (MST), respectivamente, quando comparados com o tratamento controle, porém não houve efeito da inoculação de actinomicetos no composto orgânico. Nas condições em que este estudo foi realizado foi possível concluir que a adubação com composto orgânico de capim elefante influenciou positivamente a produção de biomassa seca da L. alba, mas a inoculação dos compostos com actinomicetos não exerceu influência.

L. alba is a species of the family Verbenaceae widely used by the Brazilian population, because of the soothing, gentle antispasmodic, analgesic, expectorant, sedative, anxiolytic and smoothly. For the implementation of the experiment produced organic compound of elephant grass (Pennisetum purpureum Shum.) + manure at 70% plant material and 30% manure, uninoculated and inoculated with the actinomycete Streptomyces genus, AC16, AC26, AC92 and AC103. The compounds were placed in polyethylene bags containing 10.0 kg of soil added in a proportion equivalent to 20 t ha-1 and re-apply after the first harvest. The harvests of the shoots were taken at 75 and 165 days after transplantation. The roots were harvested after the second harvest. Dealing with organic fertilization promoted the average increase in biomass production of lemon grass 184, 83, 125, 115 and 122% for the dry stem biomass (MSPA) in the first harvest, second harvest of MSPA, total shoot biomass (MSTPA), dry biomass of the root (MSR) and the total crop biomass (MST), respectively, compared with the control, but no effect of inoculation of actinomycetes in compost. Under the conditions of this study was conducted, it was concluded that the organic compound fertilizer with elephant grass positively influenced the production of dry biomass of L. alba, but the injection of the compounds of the actinomycetes, without influence.

Effect of antipyrine on the gastric emptying of liquid in rats.

Antipyrine (At) and dipyrone (Dp) delay gastric emptying (GE) in rats. The objective of the present study was to assess the effects of intravenous (iv) and intracerebroventricular (icv) administration of At and Dp on the GE of liquid by rats. GE was assessed in male Wistar rats (5-10 in each group) 10 min after the icv or iv drug injection by measuring percent gastric retention (%GR) of a saline test meal labeled with phenol red 10 min after administration by gavage. The At iv group was significantly higher (64.4 +/- 2.6%) compared to control (33.4 +/- 1.5%) but did not differ from the Dp group (54.3 +/- 3.8%). After icv administration of At, %GR (34.2 +/- 2%) did not differ from control (32.6 +/- 1.9%), but was significantly higher after Dp (54.5 +/- 2.3%). Subdiaphragmatic vagotomy significantly reduced %GR in the At group (30.2 +/- 0.7%) compared to the sham group, but was significantly higher than in the controls (23.0 +/- 0.5%). In the animals treated with At iv, baclofen significantly reduced %GR (28.3 +/- 2.4%) compared to vehicle-treated animals (55.2 +/- 3.2%). The same occurred in the animals treated iv with vehicle and icv with baclofen. Although vagotomy and baclofen reduced %GR per se, the reduction was twice more marked in the animals treated with At. The results suggest that At administered iv, but not icv, delays GE of liquid in rats with the participation, at least in part, of the vagus nerve and that this phenomenon is blocked by the activation of GABA B receptors in the central nervous system.

Effect of antipyrine on the gastric emptying of liquid in rats

Antipyrine (At) and dipyrone (Dp) delay gastric emptying (GE) in rats. The objective of the present study was to assess the effects of intravenous (iv) and intracerebroventricular (icv) administration of At and Dp on the GE of liquid by rats. GE was assessed in male Wistar rats (5-10 in each group) 10 min after the icv or iv drug injection by measuring percent gastric retention ( percentGR) of a saline test meal labeled with phenol red 10 min after administration by gavage. The At iv group was significantly higher (64.4 ± 2.6 percent) compared to control (33.4 ± 1.5 percent) but did not differ from the Dp group (54.3 ± 3.8 percent). After icv administration of At, percentGR (34.2 ± 2 percent) did not differ from control (32.6 ± 1.9 percent), but was significantly higher after Dp (54.5 ± 2.3 percent). Subdiaphragmatic vagotomy significantly reduced percentGR in the At group (30.2 ± 0.7 percent) compared to the sham group, but was significantly higher than in the controls (23.0 ± 0.5 percent). In the animals treated with At iv, baclofen significantly reduced percentGR (28.3 ± 2.4 percent) compared to vehicle-treated animals (55.2 ± 3.2 percent). The same occurred in the animals treated iv with vehicle and icv with baclofen. Although vagotomy and baclofen reduced percentGR per se, the reduction was twice more marked in the animals treated with At. The results suggest that At administered iv, but not icv, delays GE of liquid in rats with the participation, at least in part, of the vagus nerve and that this phenomenon is blocked by the activation of GABA B receptors in the central nervous system.

PLA2/PGE2 are involved in the inhibitory effect of bradykinin on the angiotensin-(1-7)-stimulated Na(+)-ATPase activity of the proximal tubule.

Recently, we demonstrated that bradykinin (BK) counteracts the stimulatory effect of Ang-(1-7) on the Na(+)-ATPase activity from basolateral membrane of the proximal tubule through B2 receptor. In the present paper, the signaling pathway involved in the inhibitory response of the Na(+)-ATPase activity to BK was investigated. The following results indicate that the phospholipase A2 (PLA2)/COX/prostaglandin E (PGE2) pathway is implicated in this process: (1) The inhibitory effect of BK on Ang-(1-7)-stimulated enzyme is abolished in a dose-dependent manner by quinacrine (10(-9)-10(-6)M), a nonspecific PLA2 inhibitor, and by PACOCF3 (10(-7)M), an inhibitor of a Ca(2+)-independent PLA2. However, AACOCF3 (2 x 10(-4) M), an inhibitor of the cytosolic PLA2, does not modify the inhibitory effect of BK. (2) The inhibitory effect of BK on the Ang-(1-7)-stimulated enzyme is reversed by cyclooxygenase (COX) inhibitors diclofenac (10(-12) M) and indomethacin (10(-12) M). (3) PGE2 (10(-12)-10(-5) M) inhibits the Na(+)-ATPase activity in a dose dependent manner. (4)The inhibitory effects of PGE2 and BK on the Na(+)-ATPase activity are not cumulative. (5) PGE2 (10(-12)-10(-8) M) counteracts the stimulatory effect of Ang-(1-7) on the enzyme activity in a dose-dependent manner.

Impaired host defense to Klebsiella pneumoniae infection in mice treated with the PDE4 inhibitor rolipram.

The increase in levels of cAMP in leukocytes by selective inhibitors of PDE4 may result in reduction of inflammation, and may be useful in the treatment of pulmonary inflammatory disorders in humans. Here, we have assessed whether oral treatment with the prototype PDE4 inhibitor, rolipram, interfered with the antibacterial host response following pulmonary infection of mice with Klebsiella pneumoniae. K. pneumoniae infection induced a marked increase in the recruitment of neutrophils to the lungs and the production of proinflammatory cytokines and chemokines, including tumor necrosis factor-alpha (TNF-alpha) and keratinocyte-derived chemokine (KC), in bronchoalveolar (BAL) fluid and lung tissue. There were also detectable amounts of interleukin-10 (IL-10) and significant lethality. Treatment with rolipram (3-30 mg kg-1) was associated with earlier lethality and significant inhibition of the TNF-alpha production. This was associated with enhanced production of IL-10 in lung tissue of rolipram-treated animals. Rolipram treatment did not affect KC expression and the recruitment of neutrophils in the lung tissue. Over 70% of neutrophils that migrated into the BAL fluid following K. pneumoniae infection ingested bacteria. Treatment with rolipram inhibited the percentage of neutrophils undergoing phagocytosis of K. pneumoniae in a dose-dependent manner. Maximal inhibition (62%) occurred at doses equal to or greater than 10 mg kg-1. Thus, treatment of mice with the PDE4 inhibitor rolipram is accompanied by earlier lethality, enhanced bacterial load and decreased capacity of the responding host to produce TNF-alpha and of neutrophils to phagocytose bacteria. It will be important to investigate whether the shown ability of PDE4 inhibitors to inhibit neutrophil phagocytosis and control experimental bacterial infection will translate into an inhibition of the ability of neutrophils to deal with infectious microorganisms in the clinical setting.

Role of the platelet-activating factor (PAF) receptor during pulmonary infection with gram negative bacteria.

The lipid mediator PAF plays an important role in the phagocytosis of particles, including bacteria, and consequent production of pro-inflammatory cytokines, such as TNF-alpha and IL-8. Using a PAF receptor antagonist (UK-74,505) and PAF receptor knock-out mice, we have investigated the relevance of PAF for the inflammatory changes and lethality after pulmonary infection with the gram-negative bacteria Klebsiella pneumoniae in mice. At an inoculum of 3 x 10(6) bacteria, there was marked pulmonary (bronchoalveolar lavage and lung) neutrophilia that started early (2.5 h after infection) and peaked at 48 h. All animals were dead by day 4 of infection. The chemokine KC and the pro-inflammatory cytokine TNF-alpha increased rapidly and persisted for 48 h in the lungs. Pretreatment with UK-74,505 (30 mg kg(-1) per day, p.o.) had no significant effects on the number of infiltrating neutrophils in BAL fluid or lung tissue, as assessed by histology and measuring myeloperoxidase, or on the concentrations of KC. In contrast, concentrations of TNF-alpha and the number of bacteria inside neutrophils were significantly diminished. In order to support a role for the PAF during K. pneumoniae infection, experiments were also carried out in PAFR-deficient mice. In the latter animals, lethality occurred earlier than in wild-type controls. This was associated with greater number of bacteria in lung tissue and diminished percentage of neutrophils containing bacteria in their cytoplasm. Our results suggest that PAF, acting on its receptor, plays a protective role during infection with K. pneumoniae in mice.

Dibutyryl-cyclic GMP induces peripheral antinociception via activation of ATP-sensitive K(+) channels in the rat PGE2-induced hyperalgesic paw.

1. Using the rat paw pressure test, in which increased sensitivity is induced by intraplantar injection of prostaglandin E2, we studied the action of several K(+) channel blockers in order to determine what types of K(+) channels could be involved in the peripheral antinociception induced by dibutyrylguanosine 3 : 5'-cyclic monophosphate (DbcGMP), a membrane permeable analogue of cyclic GMP. 2. DbcGMP elicited a dose-dependent (50, 75, 100 and 200 microg paw(-1)) peripheral antinociceptive effect. The effect of the 100 microg dose of DbcGMP was considered to be local since only a higher dose (300 microg paw(-1)) produced antinociception in the contralateral paw. 3. The antinociceptive effect of DbcGMP (100 microg paw(-1)) was dose-dependently antagonized by intraplantar administration of the sulphonylureas tolbutamide (20, 40 and 160 microg) and glibenclamide (40, 80 and 160 microg), selective blockers of ATP-sensitive K(+) channels. 4. Charybdotoxin (2 microg paw(-1)), a selective blocker of high conductance Ca(2+)-activated K(+) channels, and apamin (10 microg paw(-1)), a selective blocker of low conductance Ca(2+)-activated K(+) channels, did not modify the peripheral antinociception induced by DbcGMP. 5. Tetraethylammonium (2 mg paw(-1)), 4-aminopyridine (200 microg paw(-1)) and cesium (800 paw(-1)), non-selective voltage-gated potassium channel blockers, also had no effect. 6. Based on this experimental evidence, we conclude that the activation of ATP-sensitive K(+) channels could be the mechanism by which DbcGMP induces peripheral antinociception, and that Ca(2+)-activated K(+) channels and voltage-dependent K(+) channels appear not to be involved in the process.

Serum electrolyte and total protein alterations in Pantaneiro horse during long distance exercise

Blood samples were taken from eight Pantaneiro horses during a 76Km endurance ride. The horses were divided into two groups: 1- four horses kept on native pasture, without working and with no supplementation during one month before the ride, 2- four horses kept on native pasture with supplementation and submitted to work during one month before the ride. Serum concentration of total protein, albumin, sodium, potassium, chloride, calcium and phosphorus were measured. Samples were taken before the ride (preride), during the mid point (midride), at the end of the ride (postride) and after a 30-minute recovery period (rest). Sweat samples were collected from five horses at the end of the ride to measure sodium, potassium, and chloride. In the groups, there was a significant decrease in calcium and potassium, and an increase in sodium and phosphorus during the ride. Heart rate values after 30 minutes of rest indicated a good recovery response

Activation of ATP-sensitive K(+) channels: mechanism of peripheral antinociceptive action of the nitric oxide donor, sodium nitroprusside.

Using the rat paw pressure test, in which sensitivity is increased by intraplantar injection of prostaglandin E(2) (PGE(2)), we conducted a study using several K(+) channel blockers. The objective was to determine what types of K(+) channels could be involved in the peripheral antinociceptive action of the nitric oxide donor sodium nitroprusside (SNP). SNP elicited a dose-dependent (250 and 500 microgram/paw) peripheral antinociceptive effect, which was considered local, since only higher doses produced an effect in the contralateral paw. The effect of SNP (500 microgram/paw) was dose-dependently antagonized by intraplantar administration of the sulfonylureas tolbutamide (20, 40 and 160 microgram) and glibenclamide (40, 80 and 160 microgram), selective blockers of ATP-sensitive K(+) channels. Charybdotoxin (2 microgram/paw), a selective blocker of high conductance Ca(2+)-activated K(+) channels, and apamin (10 microgram/paw), a selective blocker of low conductance Ca(2+)-activated K(+) channels, did not modify the peripheral antinociception induced by SNP. Tetraethylammonium (2 mg/paw), 4-aminopyridine (200 microgram/paw) and cesium (800 microgram/paw) also had no effect. Based on this experimental evidence, we conclude that the activation of ATP-sensitive K(+) channels could be the mechanism by which nitric oxide, donated by SNP, induces peripheral antinociception, and that Ca(2+)-activated K(+) channels and voltage-dependent K(+) channels appear not to be involved in the process.

Child and maternal mortality during a period of conflict in Beira City, Mozambique.

BACKGROUND: Child mortality rates have been declining in most developing countries. We studied child and maternal mortality risk factors for child mortality in Beira city in July 1993, after a decade of conflict in Mozambique. METHODS: A community-based cluster sample survey of 4609 women of childbearing age was conducted. Indirect techniques were used to estimate child mortality ('children ever born' method and Preceding Birth Techniques (PBT) and maternal mortality (sisterhood method). Deaths among the most recent born child, born since July 1990, were classified as cases (n = 106), and two controls, matched by age and cluster, were selected per case. RESULTS: Indirect estimates of the probability of dying from birth to age 5 (deaths before age 5 years, (5)q(0) per 1000) decreased from 246 in 1977/8 to 212 in 1988/9. The PBT estimate of 1990/91 was 154 (95 percent confidence interval [CI]: 124-184), but recent deaths may have been underreported. Lack of beds in the household (odds ratio [OR] = 2.0, 95 percent CI: 1.1-3.8), absence of the father (OR = 2.4, 95 percent CI : 1.2-4.8), low paternal educational level (OR = 2.1, 95 percent CI: 0.8-5.4), young maternal age (OR = 2.0, 95 percent CI: 1.0-3.7), self-reported maternal illness (OR = 2.4, 95 percent CI : 1.2-4.9), and home delivery of the child (OR = 2.3, 95 percent CI : 1.2-4.5) were associated with increased mortality, but the sensitivity of risk factors was low. Estimated maternal mortality was 410/100 000 live births with a reference date of 1982. CONCLUSIONS: Child mortality decreased slowly over the 1980s in Beira despite poor living conditions caused by the indirect effects of the war. Coverage of health services increased over this period. The appropriateness of a risk approach to maternal-child-health care needs further evaluation.

PIP: In July 1993, public health specialists conducted a cluster sample survey of 4609 women aged 15-49 living in 3190 houses in Beira city to determine child and maternal mortality after 10 years of internal conflict in Mozambique and a nested case control study of risk factors for child mortality. The indirect estimate techniques were child ever born and preceding birth techniques for child mortality and the sisterhood method for maternal mortality. The case control study compared 106 deaths among the most recent born child born since July 1990 with two age- and cluster-matched controls. The proportion of dead sisters who died of pregnancy-related causes was only 10.3% compared to 25-33% in developing countries. In 1982, the estimated maternal mortality ratio was 410/100,000 live births. The lifetime risk of maternal mortality was 263/1000. The preceding birth technique obtained a much lower child mortality estimate than the child ever born technique (154 vs. 212/1000). The child ever born technique analyzed data from 1977-1978 to 1988-1989 and found that the probability of dying from birth to age 5 fell 14% (246-212). During this period, coverage of health services improved. Even though the preceding birth technique is usually more reliable for recent estimates, underreporting of recent child deaths likely contributed to the lower child mortality estimate. Risk factors for child mortality included no beds in the household (odds ratio [OR] = 2.02), absence of the father (OR = 2.43), low paternal educational level (OR = 2.08), young maternal age (OR = 1.96), self-reported maternal illness since birth of child (OR = 2.43), and home delivery (OR = 2.31). Yet the sensitivity of these risk factors was rather low (15-57%). These findings show that child mortality fell slowly during the 1980s despite the poor living conditions brought about by the indirect effects of the civil war. They point to the need to further evaluate the appropriateness of a risk approach to maternal and child health care needs.

[A cerebrovascular stroke in a child with an anomalous origin of the left coronary artery]. / Acidente vascular cerebral em criança portadora de origem anômala da artéria coronária esquerda.

A two-year-old male child presenting anomalous origin of the left coronary artery diagnosed by Doppler echocardiography and confirmed by angiography developed an ischemic stroke, which is a rare event in this situation. He [correction of She] had good recovery of the neurological deficit and his anomalous artery was successfully reimplanted.