Maternal low-protein diet induces changes in the cardiovascular autonomic modulation in male rat offspring.

BACKGROUND AND AIMS: Maternal undernutrition induces development of the arterial hypertension. We investigated the effects of a maternal low-protein diet on cardiovascular autonomic control in the offspring. METHODS AND RESULTS: Male Wistar rats were divided into two groups according to the diets of their mothers during gestation and lactation: the control (normal protein, NP, 17% casein; n = 14) and low-protein (LP, 8% casein; n = 14) groups. Direct measurements of arterial pressure (AP) were recorded from wakeful 90-day-old male offspring. The LP offspring presented higher mean AP than did the NP rats (NP: 93 ± 4 vs. LP: 113 ± 2 mmHg; p < 0.05), whereas the heart rate (HR) was similar in the two groups. In the spectral analysis, the LP group showed higher power at low (NP: 1.98 ± 0.25 vs. LP: 3.7 ± 0.3 mmHg²; p < 0.05) and high (NP: 1.28 ± 0.18 vs. LP: 2.13 ± 0.42 mmHg²; p < 0.05) frequencies of systolic arterial pressure (SAP). In the pulse interval, the LP group presented an increase in the LF/HF ratio (NP: 0.32 vs. LP: 0.56; p < 0.05). After propranolol (4 mg/kg, intravenous (iv)), the bradycardia was higher in the LP group (NP: -36 ± 8 vs. LP: -94 ± 12 bpm; p < 0.05), after methylatropine (2 mg/kg, iv), the tachycardia was similar to NP group. After administration of the ganglionic blocker (hexamethonium; 25 mg/kg, iv), the LP animals showed larger delta variation in the AP (NP: -33.7 ± 5 vs. LP: -53.6 ± 4 mmHg; p < 0.05). CONCLUSION: The rats subjected to protein malnutrition presented an increase in the cardiovascular sympathetic tone, which contributed to the elevated AP observed in these animals.

Anti-diabetic activity of extract from Persea americana Mill. leaf via the activation of protein kinase B (PKB/Akt) in streptozotocin-induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Persea americana Mill. (Lauraceae) have been popularly used in the treatment of diabetes in countries in Latin America and Africa. AIM OF THE STUDY: To investigate the hypoglycaemic properties and to determine the molecular mechanism by which the hydroalcoholic extract of the leaves of Persea americana reduce blood glucose levels in streptozotocin (STZ)-induced diabetes in rats via the enzymatic pathway of protein kinase B (PKB/Akt). METHODS: The hydroalcoholic extract of the leaves of Persea americana (0.15 and 0.3g/kg/day), vehicle and metformin (0.5g/kg/day) were administered orally to STZ-diabetic rats (n=7/group) for 4 weeks. Changes in body weight, food and water intake, fasting glucose levels and oral glucose tolerance were evaluated. Phosphorylation and the expression of PKB in the liver and soleus muscle were determined by Western blot. RESULTS: The hydroalcoholic extract of the leaves of Persea americana reduced blood glucose levels and improved the metabolic state of the animals. Additionally, PKB activation was observed in the liver and skeletal muscle of treated rats when compared with untreated rats. CONCLUSION: The results indicate that the hydroalcoholic extract of the leaves of Persea americana has anti-diabetic properties and possibly acts to regulate glucose uptake in liver and muscles by way of PKB/Akt activation, restoring the intracellular energy balance.

Cálculo da CI50 (concentração inibitória média) e CL50 (concentração letal média) do óleo da semente de andiroba (Carapa guianensis, Aubl.) sobre Rhipicephalus (Boophilus) microplus (Canestrini, 1887), Anocentor nitens (Neumann, 1897) e Rhipicephalus sanguineus (Latreille, 1806) (Acari: Ixodidae)

The average inhibitory concentration (CI50) and average lethal concentration (CL50) of oil obtained from the seeds of Carapa guianensis aubl were determined on oviposition and larval viability of Rhipicephalus (Boophilus) microplus (Canestrini, 1887), Anocentor nitens (Neumann, 1897) and Rhipicephalus sanguineus (Latreille, 1806) (Acari: Ixodidae). For the oviposition treatment, 10 engorged females were used at 5 different dilutions (20%, 10%, 5%, 2.5% and 1.25%). The control group of females was immersed in distilled water. Three replicates were used for each dilution. For the larval viability treatment 100 larvae ranging from 14 to 21 days of age were used at 6 dilutions (20%, 10%, 5%, 2.5%, 1.25 and 0.75%), using deionized water and Tween 80 as a dispersant. Two control groups were used, one with deionized water only and another with Tween 80 and deionized water. CI50 of 4.332, 4.850, 4.903 and CL50 of 5,228; 5,362 and 5,698 R. (B.) microplus, A. nitens and R. sanguineus were observed for oviposition and larvae respectively. The lowest concentration at which maximum effectiveness of C. guianensis oil was obtained was 10%. In conclusion this oil is toxic for these ticks and may be an alternative acaricide for tick control.

Determinou-se a CI50 (concentração inibitória média) e a CL50 (concentração letal média) do óleo da semente de andiroba (Carapa guianensis, Aubl), respectivamente, sobre a ovipostura e larvas não alimentadas de Rhipicephalus (Boophilus) microplus, Anocentor nitens e Rhipicephalus sanguineus. Para o tratamento das fêmeas utilizaram-se cinco diluições do óleo (20%, 10%, 5%, 2,5% e 1,25%), e um controle negativo com água destilada, com três repetições de 10 fêmeas ingurgitadas para cada diluição por tratamento. Para as larvas, foram preparadas seis diluições do óleo (20%, 10%, 5%, 2,5%, 1,25 e 0,75%), utilizando-se água destilada e tween 80 como dispersante, e um grupo controle com água destilada e outro com tween 80 e água destilada. Aproximadamente 100 larvas de 14 a 21 dias de idade foram utilizadas para cada diluição no teste de imersão. Foram obtidas CI50 de 4,332; 4,850; 4,903, e uma CL50 de 5,228; 5,362 e 5,698, respectivamente, para fêmeas e larvas de R. (B.) microplus, A. nitens e R. sanguineus. A menor concentração em que se observou eficácia máxima do óleo da semente de C. guianensis foi de 10%. Essa espécie possui significativo potencial no controle dos carrapatos avaliados, interferindo na sua reprodução, podendo ser no futuro uma alternativa aos carrapaticidas normalmente utilizados, após estudos mais detalhados.

Cálculo da CI50 (concentração inibitória média) e CL50 (concentração letal média) do óleo da semente de andiroba (Carapa guianensis, Aubl.) sobre Rhipicephalus (Boophilus) microplus (Canestrini, 1887), Anocentor nitens (Neumann, 1897) e Rhipicephalus sanguineus (Latreille, 1806) (Acari: Ixodidae)

The average inhibitory concentration (CI50) and average lethal concentration (CL50) of oil obtained from the seeds of Carapa guianensis aubl were determined on oviposition and larval viability of Rhipicephalus (Boophilus) microplus (Canestrini, 1887), Anocentor nitens (Neumann, 1897) and Rhipicephalus sanguineus (Latreille, 1806) (Acari: Ixodidae). For the oviposition treatment, 10 engorged females were used at 5 different dilutions (20%, 10%, 5%, 2.5% and 1.25%). The control group of females was immersed in distilled water. Three replicates were used for each dilution. For the larval viability treatment 100 larvae ranging from 14 to 21 days of age were used at 6 dilutions (20%, 10%, 5%, 2.5%, 1.25 and 0.75%), using deionized water and Tween 80 as a dispersant. Two control groups were used, one with deionized water only and another with Tween 80 and deionized water. CI50 of 4.332, 4.850, 4.903 and CL50 of 5,228; 5,362 and 5,698 R. (B.) microplus, A. nitens and R. sanguineus were observed for oviposition and larvae respectively. The lowest concentration at which maximum effectiveness of C. guianensis oil was obtained was 10%. In conclusion this oil is toxic for these ticks and may be an alternative acaricide for tick control.

Determinou-se a CI50 (concentração inibitória média) e a CL50 (concentração letal média) do óleo da semente de andiroba (Carapa guianensis, Aubl), respectivamente, sobre a ovipostura e larvas não alimentadas de Rhipicephalus (Boophilus) microplus, Anocentor nitens e Rhipicephalus sanguineus. Para o tratamento das fêmeas utilizaram-se cinco diluições do óleo (20%, 10%, 5%, 2,5% e 1,25%), e um controle negativo com água destilada, com três repetições de 10 fêmeas ingurgitadas para cada diluição por tratamento. Para as larvas, foram preparadas seis diluições do óleo (20%, 10%, 5%, 2,5%, 1,25 e 0,75%), utilizando-se água destilada e tween 80 como dispersante, e um grupo controle com água destilada e outro com tween 80 e água destilada. Aproximadamente 100 larvas de 14 a 21 dias de idade foram utilizadas para cada diluição no teste de imersão. Foram obtidas CI50 de 4,332; 4,850; 4,903, e uma CL50 de 5,228; 5,362 e 5,698, respectivamente, para fêmeas e larvas de R. (B.) microplus, A. nitens e R. sanguineus. A menor concentração em que se observou eficácia máxima do óleo da semente de C. guianensis foi de 10%. Essa espécie possui significativo potencial no controle dos carrapatos avaliados, interferindo na sua reprodução, podendo ser no futuro uma alternativa aos carrapaticidas normalmente utilizados, após estudos mais detalhados.

Hypoglycaemic activity and molecular mechanisms of Caesalpinia ferrea Martius bark extract on streptozotocin-induced diabetes in Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The tea from the stem bark of Caesalpinia ferrea Martius (Leguminosae) has been popularly used in the treatment of diabetes in Brazil. AIM OF THE STUDY: To investigate the hypoglycaemic properties and to elucidate the mechanisms by which the aqueous extract of the stem bark of Caesalpinia ferrea reduces blood glucose levels in streptozotocin-induced diabetic rats via the enzymatic pathways of protein kinase B (PKB/Akt), AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC). MATERIALS AND METHODS: The aqueous extract of the stem bark of Caesalpinia ferrea (300 and 450 mg/kg/day), vehicle and metformin (500 mg/kg/day) were administered orally to STZ-diabetic rats (n = 7/group) for 4 weeks. Changes in body weight, food and water intake, fasting glucose levels and oral glucose tolerance were evaluated. Phosphorylation (P) and the expression of Akt, AMPK and ACC in the liver and skeletal muscle were determined using Western blot. RESULTS: The aqueous extract of the stem bark of Caesalpinia ferrea reduced blood glucose levels and improved the metabolic state of the animals. P-Akt was increased in the liver and skeletal muscle of the treated animals, P-AMPK was reduced only in the skeletal muscle of these animals and P-ACC was reduced in both when compared with untreated rats. CONCLUSION: The results indicate that the aqueous extract of the stem bark of Caesalpinia ferrea has hypoglycaemic properties and possibly acts to regulate glucose uptake in liver and muscles by way of Akt activation, restoring the intracellular energy balance confirmed by inhibition of AMPK activation.

Avaliação in vitro dos efeitos do óleo da semente de Carapa guianensis Aubl. sobre larvas de nematóides gastrintestinais de caprinos e ovinos / In vitro evaluation of Carapa guianensis Aubl. seed oil effects on larvae from gastrointestinal nematodes of goats and sheep

Com objetivo de avaliar in vitro a ação do óleo da semente da Carapa guianensis (Andiroba) no cultivo de larvas de nematóides gastrintestinais de animais das espécies caprina e ovina, foram testadas cinco diluições do óleo de andiroba (100, 50, 30, 25 e 10 por cento), com três repetições por tratamento, utilizando-se tween 80 como dispersante, formando-se ainda três grupos controle, um controle negativo (água destilada), outro controle negativo (água destilada + tween 80) e um controle positivo (Doramectina). A atividade da andiroba sobre os ovos de nematóides gastrintestinais foi determinada pelo cálculo dos percentuais de redução de larvas por gramas de fezes. Os resultados revelaram na espécie caprina redução altamente efetiva no número de larvas totais para os tratamentos 100, 50 e 30 por cento com médias nulas para todos os gêneros de nematóides. Na espécie ovina observou-se redução altamente efetiva no número de larvas totais em todos os tratamentos, com médias nulas nos tratamentos 100, 50 e 30 por cento. Os resultados obtidos neste experimento demonstram que o óleo da semente de Carapa guianensis possui atividade in vitro contra larvas de nematóides gastrintestinais de caprinos e ovinos.

This study aimed to evaluate the in vitro action of Carapa guianensis (Andiroba) seed oil on the cultivation of larvae from gastrointestinal nematodes of goats and sheep. Five andiroba oil dilutions (100, 50, 30, 25, and 10 percent) were assayed, with three replicates per treatment, using Tween 80 as surfactant. Three control groups were formed: a negative control (distilled water), another negative control (distilled water + Tween 80) and a positive control (Doramectin). The activity of andiroba on the eggs from gastrointestinal nematodes was obtained by calculating larva reduction percentages per gram of feces. In goats, a highly effective reduction in the total number of larvae was detected for treatments 100, 50 and 30 percent, with null means for all nematode genera. In sheep, a highly effective reduction in the total number of larvae was observed for all treatments, with null means for treatments 100, 50 and 30 percent. Such results indicate that Carapa guianensis (Andiroba) seed oil has in vitro activity against larvae from gastrointestinal nematodes of goats and sheep.

Acute and subacute toxicity of Schinus terebinthifolius bark extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Schinus terebinthifolius Raddi (Anacardiaceae) has long been used in traditional Brazilian medicine, especially to treat inflammatory and haemostatic diseases. AIM OF THE STUDY: The objective of this study was to evaluate the acute and subacute toxicity (45 days) of Schinus terebinthifolius via the oral route in Wistar rats of both sexes. MATERIALS AND METHODS: For the acute toxicity test, the dried extract of Schinus terebinthifolius bark was administered in doses from 0.625 to 5.0 g/kg (n=5/group/sex) and in the subacute toxicity test the following doses were used: 0.25, 0.625 and 1.5625 g/kg/day (n=13/group/sex), for 45 consecutive days. RESULTS: In the acute toxicity test, Schinus terebinthifolius did not produce any toxic signs or deaths. The subacute treatment with Schinus terebinthifolius did not alter either the body weight gain or the food and water consumption. The hematological and biochemical analysis did not show significant differences in any of the parameters examined in female or male groups, except in two male groups, in which the treatment with Schinus terebinthifolius (0.25 and 0.625 g/kg) induced an increase of mean corpuscular volume values (2.9 and 2.6%, respectively). These variations are within the physiological limits described for the specie and does not have clinical relevance. CONCLUSION: The acute and subacute administration of the dried extract of Schinus terebinthifolius bark did not produced toxic effects in Wistar rats.

Potencial acaricida do óleo de andiroba Carapa guianensis Aubl. sobre fêmeas adultas ingurgitadas de Anocentor nitens Neumann, 1897 e Rhipicephalus sanguineus Latreille, 1806 / Acaricide potencial of andiroba (Carapa guianensis Aubl. ) oil on engorged adult females of Anocentor nitens (Neumann, 1897) and Rhipicephalus sanguineus (Latreille, 1806)

Avaliou-se o potencial acaricida in vitro do óleo da semente da andiroba (Carapa guianensis) sobre fêmeas ingurgitadas de Anocentor nitens (n=210) e Rhipicephalus sanguineus (n=140), coletadas manualmente, respectivamente, de equinos e de cães naturalmente infestados. Para o teste de imersão, empregaram-se cinco diluições do óleo de andiroba, 100 por cento, 50 por cento, 30 por cento, 25 por cento e 10 por cento, em água destilada, utilizando-se tween 80 como dispersante. No teste com A. nitens, foram usadas três repetições para cada diluição, utilizando-se 10 fêmeas ingurgitadas para cada tratamento. No teste com R. sanguineus, usaram-se duas repetições, e formaram-se, ainda, dois grupos-controle para cada espécie de ixodídeo, um com água destilada e outro com tween 80 mais água destilada. Após os testes, as fêmeas foram mantidas em laboratório sob temperatura ambiente. Observou-se mortalidade das fêmeas ingurgitadas e redução de postura, neste caso, com ovos inférteis, demonstrando eficácia de 100 por cento nas duas espécies em todas as diluições testadas. Os dados obtidos evidenciaram a potencialidade do uso do extrato de andiroba contra A. nitens e R. sanguineus.(AU)

In vitro acaricide potential of the oil from andiroba seed (Carapa guianensis) was evaluated on engorged females of Anocentor nitens (n=210) and Rhipicephalus sanguineus (n=140) manually collected, from horses and dogs naturally infested, respectively. Five dilutions, 100 percent, 50 percent, 30 percent, 25 percent, and 10 percent of andiroba seed oil in deionized water, using tween 80 as dispersant, were employed for the engorged females immersion test. For A. nitens test, three repetitions were made with each dilution, using 10 engorged females for each treatment, and two repetitions for R. sanguineus test. Two control groups were used for each tick species, one with deionized water and another one with tween 80 and deionized water. After the tests, the females were kept in the laboratory under room temperature. Engorged female mortality and oviposition reduction were observed with infertile eggs, showing 100 percent of efficacy in the two species in all tested dilutions. The obtained data demonstrated the potential use of andiroba seed extract against A. nitens and R. sanguineus.(AU)

Potencial acaricida do óleo de andiroba Carapa guianensis Aubl. sobre fêmeas adultas ingurgitadas de Anocentor nitens Neumann, 1897 e Rhipicephalus sanguineus Latreille, 1806 / Acaricide potencial of andiroba (Carapa guianensis Aubl.) oil on engorged adult females of Anocentor nitens (Neumann, 1897) and Rhipicephalus sanguineus (Latreille, 1806)

Avaliou-se o potencial acaricida in vitro do óleo da semente da andiroba (Carapa guianensis) sobre fêmeas ingurgitadas de Anocentor nitens (n=210) e Rhipicephalus sanguineus (n=140), coletadas manualmente, respectivamente, de equinos e de cães naturalmente infestados. Para o teste de imersão, empregaram-se cinco diluições do óleo de andiroba, 100 por cento, 50 por cento, 30 por cento, 25 por cento e 10 por cento, em água destilada, utilizando-se tween 80 como dispersante. No teste com A. nitens, foram usadas três repetições para cada diluição, utilizando-se 10 fêmeas ingurgitadas para cada tratamento. No teste com R. sanguineus, usaram-se duas repetições, e formaram-se, ainda, dois grupos-controle para cada espécie de ixodídeo, um com água destilada e outro com tween 80 mais água destilada. Após os testes, as fêmeas foram mantidas em laboratório sob temperatura ambiente. Observou-se mortalidade das fêmeas ingurgitadas e redução de postura, neste caso, com ovos inférteis, demonstrando eficácia de 100 por cento nas duas espécies em todas as diluições testadas. Os dados obtidos evidenciaram a potencialidade do uso do extrato de andiroba contra A. nitens e R. sanguineus.

In vitro acaricide potential of the oil from andiroba seed (Carapa guianensis) was evaluated on engorged females of Anocentor nitens (n=210) and Rhipicephalus sanguineus (n=140) manually collected, from horses and dogs naturally infested, respectively. Five dilutions, 100 percent, 50 percent, 30 percent, 25 percent, and 10 percent of andiroba seed oil in deionized water, using tween 80 as dispersant, were employed for the engorged females immersion test. For A. nitens test, three repetitions were made with each dilution, using 10 engorged females for each treatment, and two repetitions for R. sanguineus test. Two control groups were used for each tick species, one with deionized water and another one with tween 80 and deionized water. After the tests, the females were kept in the laboratory under room temperature. Engorged female mortality and oviposition reduction were observed with infertile eggs, showing 100 percent of efficacy in the two species in all tested dilutions. The obtained data demonstrated the potential use of andiroba seed extract against A. nitens and R. sanguineus.

Toxicological reproductive study of Cassia occidentalis L. in female Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Cassia occidentalis L. (Leguminosae) has long been used as natural medicine in rainforests and other tropical regions for the treatment of inflammation, fever, liver disorders, constipation, worms, fungal infections, ulcers, respiratory infections, snakebite and as a potent abortifacient. AIM OF THE STUDY: This study has investigated the effects of oral sub-acute administration of Cassia occidentalis during pregnancy in female Wistar rats. MATERIALS AND METHODS: Three groups of pregnant rats were treated orally from the 1st to the 6th day (pre-implantation period) and from the 7th to the 14th day (organogenic period) of pregnancy, with doses of 250 and 500 mg/kg. On the 20th day of pregnancy, the animals were euthanized and reproductive parameters evaluated. RESULTS: The results revealed no statistically significant differences between the control and treated groups in terms of offspring/dam relationship; fetuses, placentae and ovaries weights; number of implantation and resorption sites; number of corpora lutea in the ovaries and pre- and post-implantation loss rates. However, the presence of dead fetuses was registered in both doses of 250 and 500 mg/kg of Cassia occidentalis. CONCLUSIONS: Further studies should therefore be conducted to obtain more detailed characteristics of the toxic effects of this species, the use of which is not recommended during pregnancy.

Acute and subacute toxicity of the Carapa guianensis Aublet (Meliaceae) seed oil.

Carapa guianensis (Meliaceae), known as Andiroba in Brazil, has been used by Amazon Rainforest indigenous communities for treatment of coughs, convulsions, skin diseases, arthritis, rheumatism, ear infections, to heal wounds and bruises and as an insect repellent. Carapa guianensis seed oil (SO) was evaluated for its acute and subacute toxicity (30 days) by the oral route in Wistar rats. In the acute toxicity test, SO (0.625-5.0g/kg, n=5/sex) did not produce any hazardous symptoms or deaths. The subacute treatment with SO (0.375, 0.75 and 1.5g/kg, n=10/group) failed to change body weight gain, food and water consumption. Hematological analysis showed no significant differences in any of the parameters examined. However, in the biochemical parameters, there was an increase in the alanine aminotransferase (ALT) serum level (29%) in the group SO 1.5g/kg. In addition, absolute and relative liver weights were increased at the doses of 0.75g/kg (23.4 and 19.1%) and 1.5g/kg (18.7 and 33.1%). In conclusion, acute and subacute administration of Carapa guianensis seed oil did not produce toxic effects in male Wistar rats. However, the increase in the ALT serum level and in both absolute and relative liver weights may indicate a possible hepatic toxicity.

A toxicological evaluation of the effect of Carapa guianensis Aublet on pregnancy in Wistar rats.

The effects of the administration of Carapa guianensis Aublet (Meliaceae) seed oil were investigated during pregnancy in female Wistar rats. Five groups of pregnant rats (n=5-9 per group) were treated orally from the 7th to the 14th day of pregnancy (organogenic period), at doses of: 0, 0.375, 0.75, 1.5 and 3.0gkg(-1). On the 20th day of pregnancy, the animals were sacrificed and laparotomized to evaluate reproductive parameters. The results showed that there was no difference between the control and treated groups in terms of the number of live and dead fetuses, the dam-offspring relationship, the weight of the fetus, the weight of the placentae and ovaries, the number of implantation sites, the number of resorption sites, the number of corpora lutea in the ovaries, and the pre- and post-implantation loss rates. It is therefore concluded that administration of Carapa guianensis seed oil did not bring about any toxic effect on pregnancy in Wistar rats.

Synthesis and schistosomicidal activity of new substituted thioxo-imidazolidine compounds.

Synthesis and physico-chemical properties of 3-benzyl-5-(4-fluoro-benzylidene)-1-methyl-2-thioxo-imidazolidin-4-ones, 5-benzylidene-3-(4-nitro-benzyl)-2-thioxo-imidazolidin-4-ones and 4-acridin-9-ylmethylene-1-benzyl-5-thioxo-imidazolidin-2-ones compounds are described. These thioxo-imidazolidine derivatives were prepared by alkylation and condensation with 4-fluoro-benzaldehyde or nucleophilic Michael addition with cyanoacrylates. The schistosomicidal activity of 3-benzyl-5-(4-fluoro-benzylidene)-1-methyl-2-thioxo-imidazolidin-4-one compounds was evaluated.

Antiinflammatory and chronic toxicity study of the leaves of Ageratum conyzoides L. in rats.

The hydroalcoholic extract (HAE) of Ageratum conyzoides leaves was studied for its antiinflammatory effect on subacute (cotton pellet-induced granuloma) and chronic (formaldehyde-induced arthritis) models of inflammation in rats. The absence or presence of toxicity by prolonged use of HAE was also evaluated through biochemical and hematological analysis of rats blood samples using daily oral doses of 250 or 500 mg/kg body wt., during 90 days. The results showed that the group of rats treated with HAE (250 mg/kg body wt.; p.o.) had a 38.7% (p < 0.05) reduction in cotton-pellet granuloma. The development of chronically induced paw edema was also reduced significantly (p < 0.05) by the plant extract. The toxicity study did not show any treatment-related abnormalities in biochemical and hematological parameters. The biochemical analysis from blood samples drawn from group of rats treated orally with 500 mg/kg body wt. did, however, present 30.2% (p < 0.05) reduction of SGPT activity as compared to the corresponding control group. These results confirm the antiinflammatory properties of A. conyzoides, with no apparent hepatotoxicity.

Synthesis, anti-inflammatory and antimicrobial activities of new 1,2,4-oxadiazoles peptidomimetics.

A new series of 1,2,4-oxadizoles 6a-g have been synthesised in good yields using the peptide synthesis strategy. The prepared compounds were tested for anti-inflammatory and antimicrobial activities. The anti-inflammatory activities were determined in the rat paw oedema induced by carrageenin. Compounds 6a, c, f and g (i.v.) significantly inhibited the rat paw oedema induced by carrageenin depending upon the dose employed. The compounds were also evaluated for their in vitro antimicrobial activity. Some compounds were found to have significant activity against Gram positive and Gram negative microorganisms.

Quantitative analysis of the high-affinity binding sites for [3H]ouabain in the rat vas deferens and their immunological identification as the alpha 2 isoform of Na+/K(+)-ATPase.

Binding assays were performed with [3H]ouabain to investigate the presence of, and to characterize, a Na+/K(+)-ATPase isoform with high affinity for cardiac glycosides in the rat vas deferens. Nonlinear regression analysis of equilibrium experiments carried out with crude preparations in a Mg-Pi medium indicated the presence of high-affinity sites characterized with good precision (individual coefficients of variation = 11-35%) by their density (Bmax = 0.42 to 0.72 pmol/mg protein) and dissociation constant (Kd = 0.069 to 0.136 microM) values. The values of the dissociation rate constant (kappa-1) and the association rate constant (kappa+1) for these sites were 0.151 to 0.267 min-1 and 2.87 to 3.60 microM-1.min-1, respectively. A higher number of low-affinity sites (Kd around 15 microM), supposed to correspond to the alpha 1 isoform, was also identified, but their Kd and Bmax values were not quantified precisely in this crude preparation. Western blot assays indicated hybridization with specific anti-alpha 1 and anti-alpha 2 isoform antibodies but not with anti-alpha 3 isoform antibody. Taken together, the present results indicate the existence of a low proportion of the alpha 2 isoform of Na+/K(+)-ATPase in the rat vas deferens that can be quantified precisely by [3H]ouabain binding even in a crude membrane preparation that is suitable for studies under conditions of plasticity.

Decreased density of binding sites for the Ca2+ channel antagonist [3H]isradipine after denervation of rat vas deferens.

Radioligand binding assays were performed with the selective antagonist of dihydropyridine-sensitive Ca2+ channels [3H]PN200-110 (isradipine) in rat vas deferens, before and 7 days after denervation, and data were compared with those obtained for K(+)-induced contractions, which are Ca(2+)-dependent. The density (Bmax) of dihydropyridine binding sites was decreased to almost one-third of its normal value after denervation. The respective affinity (KD) was not significantly changed. In addition, it was observed that the K(+)-induced tonic contraction, which corresponded to 55 +/- 2% of the respective phasic contraction, was decreased to 41 +/- 3% after denervation. It is assumed that the decreased density of Ca2+ channels causes a decrease in K(+)-induced influx of Ca2+ and consequently of the corresponding tonic contraction. These results indicate that autonomic innervation can regulate the density of dihydropyridine-sensitive Ca2+ channels in the rat vas deferens.