Chemical constituents and antioxidant activity from leaves extracts of terminalia fogiafolia mart. et zucc

CHEMICAL CONSTITUENTS and ANTIOXIDANT ACTIVITY FROM LEAVES EXTRACTS of Terminalia fagifolia Mart. et Zucc. Phytochemical investigation of ethanolic leaves extracts of T. fagifolia led to the isolation of (+)-catechin, sitosterol-3-O-beta-D-glucopyranoside, alpha- and beta-tocopherol, a mixture of lupeol, alpha- and beta-amyrin, sitosterol and a mixture of glicosid flavonoids (CP-13). The structures of these compounds were identified by (1)H and (13)C NMR spectral analysis and comparison with literature data. Absolute configuration of the catechin was determinate by circular dichroism. Antioxidant activity (EC(50)), evaluated by 2,2-diphenyl-1-picrylhidrazyl (DPPH) assay system, decreased in the order: (+)-catechin > hydroalcoholic fraction > CP-13 > aqueous fraction > EtOH extract.

Paracoccidioides brasifiensis killing by IFN-gamma, TNF-alpha and GM-CSF activated human neutrophils: role for oxygen metabolites

Paracoccidioidomycosis, a deep mycosis endemic in Latin America, is a chronic granulomatous disease caused by the fungus Paracoccidioides brasiliensis. Phagocytic cells play a critical role against the fungus and several papers show the effects of activator and suppressive cytokines on macrophage and monocyte functions. However, the studies focusing on polymorphonuclear neutrophils (PMNs) antifungal functions are scarcer. Thus, the objective of the present paper was to assess the capacity of human PMNs to kill virulent P brasiliensis strain in vitro, before and after priming with different cytokines. Moreover, the involvement of oxygen metabolites in this activity was evaluated. Nonactivated cells failed to exhibit antifungal activity. However, when these cells were IFN-gamma, TNF-alpha or GM-CSF activated, a significative fungicidal activity was detected. This process was significantly inhibited when P brasiliensis challenge occurred in presence of catalase (CAT - a scavenger of H2O2) and superoxide dismutase (SOD - a scavenger of superoxide anion). From these results it is concluded that cytokines activation is required for P brasiliensis killing by human PMNs, and that H2O2 and Superoxide anion participate as effectors molecules in this process.

Granulocyte macrophage colony-stimulating factor enhances the modulatory effect of cytokines on monocyte-derived multinucleated giant cell formation and fungicidal activity against Paracoccidioides brasiliensis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Killing of Paracoccidioides brasiliensis yeast cells by IFN-gamma and TNF-alpha activated murine peritoneal macrophages: evidence of H(2)O(2) and NO effector mechanisms

Paracoccidioidomycosis is a deep mycosis, endemic in Latin America, caused by Paracoccidioides brasiliensis. Macrophage activation by cytokines is the major effector mechanism against this fungus. This work aimed at a better understanding of the interaction between yeast cells-murine peritoneal macrophages and the cytokine signals required for the effective killing of high virulence yeast-form of P. brasiliensis. In addition, the killing effector mechanisms dependent on the generation of reactive oxygen or nitrogen intermediates were investigated. Cell preincubation with IFN-gamma or TNF-alpha, at adequate doses, resulted in effective yeast killing as demonstrated in short-term (4-h) assays. Both, IFN-gamma and TNF-alpha activation were associated with higher levels of H(2)O(2) and NO when compared to nonactivation. Treatment with catalase (CAT), a H(2)O(2) scavenger, and N(G)-monomethyl-L-arginine (L-NMMA), a nitric oxide synthase inhibitor, reverted the killing effect of activated cells. Taken together, these results suggest that both oxygen and L-arginine-nitric oxide pathways play a role in the killing of highly virulent P. brasiliensis.

Increased Reactive Oxygen Species and Tumor Necrosis Factor-Alpha Production by Monocytes are Associated with Elevated Levels of Uric Acid in Pre-Eclamptic Women

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Enhanced natural killer activity and production of pro-inflammatory cytokines in mice selected for high acute inflammatory response (AIRmax)

Strains of mice with maximal and minimal acute inflammatory responsiveness (AIRmax and AIRmin, respectively) were developed through selective breeding based on their high- or low-acute inflammatory responsiveness. Previous reports have shown that AIRmax mice are more resistant to the development of a variety of tumours than AIRmin mice, including spontaneous metastasis of murine melanoma. Natural killer activity is involved in immunosurveillance against tumour development, so we analysed the number and activity of natural killer cells (CD49b(+)), T-lymphocyte subsets and in vitro cytokine production by spleen cells of normal AIRmax and AIRmin mice. Analysis of lymphocyte subsets by flow cytometry showed that AIRmax mice had a higher relative number of CD49b(+) cells than AIRmin mice, as well as cytolytic activity against Yac.1 target cells. The number of CD3(+) CD8(+) cells was also higher in AIRmax mice. These findings were associated with the ability of spleen cells from AIRmax mice in vitro to produce higher levels of the pro-inflammatory cytokines tumour necrosis factor-alpha, interleukin-12p40 and interferon-gamma but not the anti-inflammatory interleukin-10. Taken together, our data suggest that the selective breeding to achieve the AIRmax and AIRmin strains was able to polarize the genes associated with cytotoxic activity, which can be responsible for the antitumour resistance observed in AIRmax mice.

Salivary alpha amylase and cortisol levels in children with global developmental delay and their relation with the expectation of dental care and behavior during the intervention

The purpose of this study was to analyze the alpha-amylase (sAA) and cortisol levels in children with Global developmental delay (GDD) before and after dental treatment and its association with the children's behavior during treatment. The morning salivary cortisol levels and activity of sAA of 33 children with GDD were evaluated before and after dental treatment and were compared to 19 healthy children. The behavior of children with GDD during dental care was assessed by the Frankl scale. Children with GDD showed lower levels of sAA activity than healthy children, but this result was not significant. The salivary cortisol levels were similar between GOD and healthy children. GDD children showed increased levels of sAA (but not cortisol) prior to the dental treatment as compared to the post-treatment phase. GOD children who showed less favorable behavior during dental care had higher levels of sAA and salivary cortisol than GOD children with more favorable behavior, but only the sAA results were significant. In conclusion, GOD children show hyperactivity of the SNS-axis in anticipation of dental treatment which indicates the need for strategies to reduce their anxiety levels before and during dental care. (C) 2011 Elsevier Ltd. All rights reserved.

Platelet-rich plasma stimulates cytokine expression and alkaline phosphatase activity in osteoblast-derived osteosarcoma cells

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Tumor Necrosis Factor alpha and Interleukin-1 beta Modulate Calcium and Nitric Oxide Signaling in Mechanically Stimulated Osteocytes

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Activation of alpha(2)-adrenergic receptors into the lateral parabrachial nucleus enhances NaCl intake in rats

Water and NaCl intake is strongly inhibited by the activation of alpha(2)-adrenergic receptors with clonidine or moxonidine (alpha(2)-adrenergic/imidazoline agonists) injected peripherally or into the forebrain and by serotonin and cholecystokinin in the lateral parabrachial nucleus (LPBN). Considering that alpha(2)-adrenergic receptors exist in the LPBN and the similar origin of serotonergic and adrenergic afferent pathways to the LPBN, in this study we investigated the effects of bilateral injections of moxonidine alone or combined with RX 821002 (alpha(2)- adrenergic antagonist) into the LPBN on 1.8% NaCl and water intake induced by the treatment with s.c. furosemide (10 mg/kg)+captopril (5 mg/kg). Additionally, we investigated if moxonidine into the LPBN would modify furosemide+captopril-induced c-fos expression in the forebrain. Male Holtzman rats with cannulas implanted bilaterally in the LPBN were used. Contrary to forebrain injections, bilateral LPBN injections of moxonidine (0.1, 0.5 and 1 nmol/0.2 mul) strongly increased furosemide+captopril-induced 1.8% NaCl intake (16.6 +/- 2.7, 44.5 +/- 3.2 and 44.5 +/- 4.3 ml/2 h, respectively, vs. vehicle: 6.9 +/- 1.5 ml/2 h). Only the high dose of moxonidine increased water intake (23.3 +/- 3.8 ml/2 h, vs. vehicle: 12.1 +/- 2.6 ml/2 h). Prior injections of RX 821002 (10 and 20 nmol/0.2 mu1) abolished the effect of moxonidine (0.5 nmol) on 1.8% NaCl intake. Moxonidine into the LPBN did not modify furosemide+captopril-induced c-fos expression in forebrain areas related to the control of fluid-electrolyte balance. The results show that the activation of LPBN a2-adrenergic receptors enhances furosemide+captopril-induced 1.8% NaCl and water intake. This enhancement was not related to prior alteration in the activity of forebrain areas as suggested by c-fos expression. Previous and present results indicate opposite roles for alpha(2-)adrenergic receptors in the control of sodium and water intake according to their distribution in the rat brain. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.

Involvement of central alpha(1)- and mu(2)-adrenoceptors on cardiovascular responses to moxonidine

In the present study we compared the effects produced by moxonidine (alpha(2)-adrenoceptor/imidazoline agonist) injected into the 4th cerebral ventricle and into the lateral cerebral ventricle on mean arterial pressure, heart rate and on renal, mesenteric and hindquarter vascular resistances, as well as the possible action of moxonidine on central alpha(1)- or alpha(2)-adrenoceptors to produce cardiovascular responses. Male Holtzman rats (n = 7-8) anesthetized with urethane (0.5 g/kg, intravenously - i.v.) and alpha-chloralose (60 mg/kg, i.v.) were used. Moxonidine (5, 10 and 20 nmol) injected into the 4th ventricle reduced arterial pressure (-19 +/- 5, -30 +/- 7 and -43 +/- 8 mmHg vs. vehicle: 2 +/- 4 mmHg), heart rate (-10 +/- 6, - 16 +/- 7 and -27 +/- 9 beats per minute - bpm, vs. vehicle: 4 +/- 5 bpm), and renal, mesenteric and hindquarter vascular resistances. Moxonidine (5, 10 and 20 nmol) into the lateral ventricle only reduced renal vascular resistance (-77 +/- 17%, - 85 +/- 13%, -89 +/- 10% vs. vehicle: 3 +/- 4%), without changes on arterial pressure, heart rate and mesenteric and hindquarter vascular resistances. Pre-treatment with the selective alpha(2)-adrenoceptor antagonist yohimbine (80, 160 and 320 nmol) injected into the 4th ventricle attenuated the hypotension (-32 +/- 5, -25 +/- 4 and -12 +/- 6 mmHg), bradycardia (-26 +/- 11, -23 +/- 5 and -11 +/- 6 bpm) and the reduction in renal, mesenteric and hindquarter vascular resistances produced by moxonidine (20 nmol) into the 4th ventricle. Pretreatment with yohimbine (320 nmol) into the lateral ventricle did not change the renal vasodilation produced by moxonidine (20 nmol) into the lateral ventricle. The alpha(1)-adrenoceptor antagonist prazosin (320 nmol) injected into the 4th ventricle did not affect the cardiovascular effects of moxonidine. However, prazosin (80, 160 and 320 nmol) into the lateral ventricle abolished the renal vasodilation (-17 +/- 4, -6 +/- 9 and 2 +/- 11%) produced by moxonidine. The results indicate that the decrease in renal vascular resistance due to moxonidine action in the forebrain is mediated by alpha(1)-adrenoceptors, while the cardiovascular effects produced by moxonidine acting in the brainstern depend at least partially on the activation of coadrenoceptors. (c) 2007 Elsevier B.V. All rights reserved.

Severe food restriction induces myocardial dysfunction related to SERCA2 activity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The Antigerminative Activity of Twenty-Seven Monoterpenes

Monoterpenes, the main constituents of essential oils, are known for their many biological activities. The present work studied the potential biological activity of twenty-seven monoterpenes, including monoterpene hydrocarbons and oxygenated ones, against seed germination and subsequent primary radicle growth of Raphanus sativus L. (radish) and Lepidium sativum L. (garden cress), under laboratory conditions. The compounds, belonging to different chemical classes, showed different potency in affecting both parameters evaluated. The assayed compounds demonstrated a good inhibitory activity in a dose-dependent way. In general, radish seed is more sensitive than garden cress and its germination appeares more inhibited by alcohols; at the highest concentration tested, the more active substances were geraniol, borneol, (+/-)-beta-citronellol and alpha-terpineol. Geraniol and carvone inhibited, in a significant way, the germination of garden cress, at the highest concentration tested. Radicle elongation of two test species was inhibited mainly by alcohols and ketones. Carvone inhibited the radicle elongation of both seeds, at almost all concentrations assayed, while 1,8-cineole inhibited their radicle elongation at the lowest concentrations (10(-5) M, 10(-6) M).

Effects of indoramin in rat vas deferens and aorta: concomitant alpha(1)-adrenoceptor and neuronal uptake blockade

1 the actions of the alpha(1)-adrenoceptor antagonist indoramin have been examined against the contractions induced by noradrenaline in the rat vas deferens and aorta taking into account a putative neuronal uptake blocking activity of this antagonist which could. result in self-cancelling actions.2 Indoramin behaved as a simple competitive antagonist of the contractions induced by noradrenaline in the vas deferens and aorta yielding pA(2) values of 7.38 +/- 0.05 (slope = 0.98 +/- 0.03) and 6.78 +/- 0.14 (slope = 1.08 +/- 0.06), respectively.3 When the experiments were repeated in the presence of cocaine (6 mu M) the potency (pA(2)) of indoramin in antagonizing the contractions of the vas deferens to noradrenaline was increased to 8.72 +/- 0.07 (slope = 1.10 +/- 0.05) while its potency remained unchanged in the aorta (pA(2) = 6.69 +/- 0.12; slope = 1.04 +/- 0.05).4 In denervated vas deferens, indoramin antagonized the contractions to noradrenaline with a potency similar to that found in the presence of cocaine (8.79 +/- 0.07; slope = 1.09 +/- 0.06).5 It is suggested that indoramin blocks alpha(1)-adrenoceptors and neuronal uptake in rat vas deferens resulting in Schild plots with slopes not different from unity even in the absence of selective inhibition of neuronal uptake. As a major consequence of this double mechanism of action, the pA(2) values for this antagonist are underestimated when calculated in situations where the neuronal uptake is active, yielding spurious pK(B) values.

Flavonoids and antiulcerogenic activity from Byrsonima crassa leaves extracts

Byrsonima crassa Niedenzu (IK) (Malpighiaceae) is used in Brazilian folk medicine for the treatment of diseases related mainly to gastric ulcers. In this study, we evaluated the potential antiulcerogenic effect of three different extracts obtained from the leaves of Byrsonima crassa namely hydromethanolic (80% MeOH), methanolic (MeOH) and chloroformic extracts (CHCl3). The oral administration (250, 500 and 1000 mg/kg) of all the extracts reduced the formation of lesions associated with HCl/ethanol administration in mice. The 80% MeOH extract significantly reduced the incidence of gastric lesions by 74, 78 and 92% at doses of 250,500 and 1000 mg/kg, respectively (P < 0.01). The MeOH extract reduced the ulceration by 93 and 99% only at the doses of 500 and 1000 mg/kg (P < 0.01). The lower gastroprotective action (69%) was observed when animals were treated with CHCl3 extract at the dose of 1000 mg/kg (P < 0.01). Phytochemical investigation of Byrsonima crassa afforded five known substances: quercetin-3-O-beta-D-galactopyranoside, quercetin-3-O-alpha-L-arabinopyranoside, the biflavonoid amentoflavone, (+)-catechin and (-)-epicatechin. The presence of these phenolic compounds may probably explain the antiulcerogenic effect of the extracts of Byrsonima crassa leaves. (C) 2004 Elsevier B.V.. All rights reserved.