Post-cure Heat Treatments Influence the Mechanical and Optical Properties of Acrylic and Bis-acryl Composite Resins.

OBJECTIVE: To evaluate the influence of post-cure heat treatments (PCHT) on Knoop microhardness (KHN) and color change of bis-acryl composite resin (Protemp 4 - 3M ESPE, USA and PrimmaArt - FGM, Brazil) and chemically activated acrylic resins (Dencôr - Clássico, Brazil, and Duralay - Cotia, Brazil). METHODS AND MATERIALS: Specimens (12×1 mm) were prepared for each material (n=10/group). Thirty minutes after curing, the specimens were subjected to PCHT for 10 minutes at 70°, 100°, or 130°C. The control group was kept at room temperature (24°C) for the same amount of time. KHN was analyzed 24 hours after PCHT (n=10). Following Commission Internationale de l'Éclairage (CIE) Delta E 2000 (CIEDE2000 [ΔE00]), color measurements were obtained at three time points: 1. after polymerization; 2. after PCHT; and 3. after 30 days of storage in water, coffee, or red wine. Data for each material were analyzed by one-way analysis of variance (ANOVA) (p<0.05). RESULTS: The PCHT at 130°C produced the highest KHN values. Except for the 70°C groups from Dencôr and Protemp, all PCHTs increased the initial color values (p>0.05). In general, chemically activated acrylic resins showed an increase in color stability when subjected to PCHT (p>0.05). For bis-acryl composite resin, PCHT did not influence color stability (p<0.05). CONCLUSION: Overall, the results showed that PCHT increased the tested materials' color changes and Knoop microhardness. However, except for PCHT at 130°C in Duralay, the color changes remained within acceptable values. The PCHT treatment resulted in better color stability for most of the composite resins studied.

The Impact of Different Surface Treatments on Topography and Bond Strength of Resin Cement to Lithium Disilicate Glass Ceramic.

OBJECTIVE: To evaluate the influence of different surface treatments on topography, surface roughness, surface energy, and microtensile bond strength stability of resin cement to lithium disilicate glass ceramic. METHODS AND MATERIALS: Seventy disc-shaped specimens of IPS e.max Press were divided into seven groups according to the surface treatment: NT - non-treated (control); FSil - hydrofluoric acid (HF) + silane; FPSil - HF + phosphoric acid (HP) + silane; FUSil - HF + ultrasonic bath (U) + silane; FPUSil - HF + HP + U + silane; MEP - Monobond Etch and Prime (MEP); and MEPH - MEP + heating. Topography and surface roughness were evaluated using a 3D laser confocal microscope (3DLCM) and scanning electron microscopy (SEM) and surface energy with a goniometer. The microtensile bond strength (µTBS) was evaluated after storage in distilled water at 37°C for 24 hours and after thermocycling (5,000 cycles, 5°-55° C, 30-second dwell time). Data were analyzed using one-way ANOVA (surface roughness and surface energy), two-way ANOVA (µTBS), Tukey's HSD post-hoc test, and Student t-test (α=0.05). RESULTS: FUSil, FPSil, and FSil presented similar and highest surface roughness, whereas NT, FPUSil, MEP, and MEPH showed similar, and lowest, roughness values (p<0.05). FPUSil, FPSil, FUSil, and FSil presented a similar and highest surface energy. NT, MEP, and MEPH showed similar and lowest surface energy. CONCLUSION: Only FSil, FPSil, and MEPH maintained bond strength stability after thermocycling, with FPSil leading to less bond strength reduction, suggesting this protocol is more reliable for bonding resin cements to lithium disilicate glass ceramics.

Rapid and long-lasting antidepressant-like effects of ketamine and their relationship with the expression of brain enzymes, BDNF, and astrocytes

Ketamine (KET) is an N-methyl-D-aspartate (NMDA) antagonist with rapid and long-lasting antidepressant effects, but how the drug shows its sustained effects is still a matter of controversy. The objectives were to evaluate the mechanisms for KET rapid (30 min) and long-lasting (15 and 30 days after) antidepressant effects in mice. A single dose of KET (2, 5, or 10 mg/kg, po) was administered to male Swiss mice and the forced swim test (FST) was performed 30 min, 15, or 30 days later. Imipramine (IMI, 30 mg/kg, ip), a tricyclic antidepressant drug, was used as reference. The mice were euthanized, separated into two time-point groups (D1, first day after KET injection; D30, 30 days later), and brain sections were processed for glycogen synthase kinase-3 (GSK-3), histone deacetylase (HDAC), brain-derived neurotrophic factor (BDNF), and glial fibrillary acidic protein (GFAP) immunohistochemical assays. KET (5 and 10 mg/kg) presented rapid and long-lasting antidepressant-like effects. As expected, the immunoreactivities for brain GSK-3 and HDAC decreased compared to control groups in all areas (striatum, DG, CA1, CA3, and mainly pre-frontal cortex, PFC) after KET injection. Increases in BDNF immunostaining were demonstrated in the PFC, DG, CA1, and CA3 areas at D1 and D30 time-points. GFAP immunoreactivity was also increased in the PFC and striatum at both time-points. In conclusion, KET changed brain BDNF and GFAP expressions 30 days after a single administration. Although neuroplasticity could be involved in the observed effects of KET, more studies are needed to explain the mechanisms for the drug's sustained antidepressant-like effects.

Rapid and long-lasting antidepressant-like effects of ketamine and their relationship with the expression of brain enzymes, BDNF, and astrocytes.

Ketamine (KET) is an N-methyl-D-aspartate (NMDA) antagonist with rapid and long-lasting antidepressant effects, but how the drug shows its sustained effects is still a matter of controversy. The objectives were to evaluate the mechanisms for KET rapid (30 min) and long-lasting (15 and 30 days after) antidepressant effects in mice. A single dose of KET (2, 5, or 10 mg/kg, po) was administered to male Swiss mice and the forced swim test (FST) was performed 30 min, 15, or 30 days later. Imipramine (IMI, 30 mg/kg, ip), a tricyclic antidepressant drug, was used as reference. The mice were euthanized, separated into two time-point groups (D1, first day after KET injection; D30, 30 days later), and brain sections were processed for glycogen synthase kinase-3 (GSK-3), histone deacetylase (HDAC), brain-derived neurotrophic factor (BDNF), and glial fibrillary acidic protein (GFAP) immunohistochemical assays. KET (5 and 10 mg/kg) presented rapid and long-lasting antidepressant-like effects. As expected, the immunoreactivities for brain GSK-3 and HDAC decreased compared to control groups in all areas (striatum, DG, CA1, CA3, and mainly pre-frontal cortex, PFC) after KET injection. Increases in BDNF immunostaining were demonstrated in the PFC, DG, CA1, and CA3 areas at D1 and D30 time-points. GFAP immunoreactivity was also increased in the PFC and striatum at both time-points. In conclusion, KET changed brain BDNF and GFAP expressions 30 days after a single administration. Although neuroplasticity could be involved in the observed effects of KET, more studies are needed to explain the mechanisms for the drug's sustained antidepressant-like effects.

Dual immune effect of iNKT cells considering human cutaneous and visceral leishmaniasis: An example of cell plasticity according to different disease scenarios.

Although the semi-invariant natural killer T cells (iNKT) are a small subpopulation of cells in the peripheral blood, they are presumed to play a role in early stages of infection against various pathogens, including protozoa. This work investigates the activation status and cytokine profile of iNKT cells during human Leishmania infantum and Leishmania braziliensis infection. We studied iNKT cells in patients with symptomatic active visceral leishmaniasis (AVL) (n = 8), patients with symptomatic active cutaneous leishmaniasis (ACL) (n = 13), negative endemic controls (NEC) (n = 6) and non-endemic controls (NonEC) (n = 6), with and without total Leishmania antigen stimulus (TLA). The number of iNKT cells in the peripheral blood of patients with ACL and AVL unaltered in relation to control groups. Moreover, the iNKT cells from ACL showed a hyperactivation profile compared to patients with AVL. Additionally, TLA induced IFN-gamma production in iNKT cells from patients with ACL, while in iNKT of patients with AVL, TLA induced a decrease in this cytokine. Higher IL-17 and IL-10 production by iNKT cells from patients with ACL were also observed compared to all other groups. There were no changes in iNKT IL-10-producing cells in AVL after TLA stimulation. However, TLA induced increase in IL-10 in iNKT cells in patients with ACL. These findings suggest that, although iNKT cells showed distinct profiles in patients with ACL and AVL, they play a dual role in immune modulation in both Leishmania infections.

Single- and Double-Lung Transplantation: Results of an Initial Experience of 39 Cases in Ceará (Northeast Brazil).

INTRODUCTION: The lung transplantation (LTx) program began in Ceará in 2011 and the first LTx was performed on June 11, 2011. The aim of this study was to present the initial results of the 6-year experience of our program. METHODS: We retrospectively reviewed our experience on LTx from June 2011 to August 2017. Data on recipients and transoperative and postoperative outcomes were recorded in a database. RESULTS: Twenty-two (56.4%) were single LTx, 15 (38.5%) were double, and 2 (5.1%) bilateral lobar. The mean age was 47.5 ± 15 years, and 26 (66.7%) were men. Twenty-eight (71.8%) had pulmonary fibrosis; 5 (12.8%) had pulmonary emphysema, 3 (7.7%) had bronchiectasis; 2 (5.1%) had pulmonary hypertension, and 1 (2.6%) had lymphangioleiomyomatosis. Complications occurred in 82% (32/39) and in-hospital mortality was 30.8% (single LTx = 27.8% and double LTx = 33.3%). The main complications were infection in 17 (43.5%) cases and primary graft dysfunction in 7 (17.9%). There was a significant improvement in pulmonary function in the first year of follow-up (forced expiratory volume pre-LTx = 37% ± 16% and 12 months post-LTx = 72% ± 22%, P = .001); and overall survival at 36 months was 59.0%, with no difference between single- and double-lung transplants. CONCLUSIONS: Idiopathic pulmonary fibrosis was the most common underlying disease and single LTx was the most commonly performed operation. There was a high incidence of postoperative complications and in-hospital mortality, but the 36-month follow-up showed a marked improvement in lung function and a global survival similar to the literature.

NO production and potassium channels activation induced by Crotalus durissus cascavella underlie mesenteric artery relaxation.

Animal toxins are natural resources for pharmacological studies. The venom of Crotalus durissus cascavella (C.d. cascavella) may be a source in the bio-prospecting of new anti-hypertensive agents. The aim of this study was to investigate vascular effects of the venom of C.d. cascavella in normotensive rats. Studies were performed using isolated mesenteric artery segments and aortic endothelial cells. The cumulative administration of the venom of C.d. cascavella (0.001-30 µg/mL) on phenylephrine (Phe; 10 µM) pre-contracted rings induced a concentration-dependent vasorelaxation in the presence of vascular endothelium (Emax = 47.9 ± 5.0% n = 8), and its effect was almost abolished in the absence of endothelium (Emax = 5.8± 2.4% n = 5 (∗∗∗p < 0.001)). Tissue viability was maintained as there was no difference in the contractile capacity of rings before and after the administration of venom. The vasorelaxant effect of the venom was also abolished when arteries were pre-contracted with potassium chloride (KCl; 80 mM) (Emax = 6.4± 0.9% n = 5, ∗∗∗p < 0.001). When assessing the participation of endothelium-derived relaxing factors, it was noted that non-selective COX inhibition with indomethacin (10 µM) caused a significant reduction in the vasorelaxant effect of C.d. cascavella (*p < 0.05). When investigating the participation of NO released by endothelium, there was a significant reduction of the vasorelaxant effect of venom in rings treated with L-NAME (100 µM; Emax = 17.5± 2.2% n = 6; **p < 0.01). Similar results were noted in the presence of ODQ (10 µM), an inhibitor of soluble guanylyl cyclase (Emax = 11.2± 3.5%, n = 6) and PTIO (100 µM), a stable radical scavenger for nitric oxide (Emax = 10.77± 3.6%, n = 6). Moreover, the venom induced the release of NO by isolated aortic endothelial cells through amperometric studies. When assessing the participation of K+ channels on the vasodilatory response of the venom, tyrode solution with 20 mM of KCl caused a significant reduction in the relaxation response (p < 0.001) (Emax = 21.3 ± 8%, n = 7), as did inhibitor of delayed rectifier K+ channels (4-amynopiridine 1 mM; Emax = 9.5 ± 1.3, %, n = 5, ***p < 0.001), and vasorelaxation was almost abolished in the presence of Iberiotoxin (IbTx 100 nM). Therefore, these results suggest that the venom of C.d. cascavella induces vasorelaxation in superior mesenteric artery rings of normotensive rats in an endothelium-dependent manner. Specifically, the venom stimulates the generation of endothelium-derived relaxing factors, especially NO, and activates vascular smooth muscle hyperpolarization through K+ channels. These data illustrate that C.d. cascavella is a source of bioactive molecules and therefore has therapeutic potential in the treatment of cardiovascular diseases such as hypertension.

The effects of ocean acidification and a carbon dioxide capture and storage leak on the early life stages of the marine mussel Perna perna (Linneaus, 1758) and metal bioavailability.

The study assesses the effects of carbon dioxide capture and storage (CCS) leaks and ocean acidification (OA) on the metal bioavailability and reproduction of the mytilid Perna perna. In laboratory-scale experiments, CCS leakage scenarios (pH 7.0, 6.5, 6.0) and one OA (pH 7.6) scenario were tested using metal-contaminated sediment elutriates and seawater from Santos Bay. The OA treatment did not have an effect on fertilisation, while significant effects were observed in larval-development bioassays where only 16 to 27 % of larva developed normally. In treatments that simulated CO2 leaks, when compared with control, fertilisation success gradually decreased and no larva developed to the D-shaped stage. A fall in pH increased the bioavailability of metals to marine mussels. Larva shell size was significantly affected by both elutriates when compared with seawater; moreover, a significant difference occurred at pH 6.5 between elutriates in the fertilisation bioassay.

Lithium and valproate prevent methylphenidate-induced mania-like behaviors in the hole board test.

Manic bipolar is diagnosed by psychomotor agitation, increased goal-directed activity, insomnia, grandiosity, excessive speech, and risky behavior. Animal studies aimed to modeling mania are commonly based in psychostimulants-induced hyperlocomotion. The exploration of other behaviors related with mania is mandatory to investigate this phase of bipolar disorder in animals. In this study, the hole board apparatus was suggested for evaluating mania-like behaviors induced by the psychostimulant methylphenidate. The treatment with methylphenidate (10mg/kg, ip) increased locomotion in the open field test. The pretreatment with lithium (50mg/kg, ip) and valproate (400mg/kg, ip) significantly prevented the hyperlocomotion. In the hole-board test, methylphenidate increased interactions with the central and peripheral holes and the exploration of central areas. Lithium was more effective than valproate in preventing all the behavioral manifestations induced by the psychostimulant. These findings were discussed based on the ability of methylphenidate-treated mice mimicking two symptoms of mania in the hole board test: goal-directed action and risk-taking behavior. In conclusion, the results point to a new approach to study mania through the hole board apparatus. The hole board test appears to be a sensitive assay to detect the efficacy of antimanic drugs.

Beta-arrestin 2 rather than G protein efficacy determines the anxiolytic-versus antidepressant-like effects of nociceptin/orphanin FQ receptor ligands.

BACKGROUND AND PURPOSE: Nociceptin/orphanin FQ (N/OFQ) receptor (NOP) agonists produce anxiolytic-like effects in rodents while antagonists promote antidepressant-like effects. The aim of this study was to investigate the effect on anxiety and depression of NOP receptor partial agonists such as the peptides [F/G]N/OFQ(1-13)NH2 and UFP-113 and the non-peptide AT-090. EXPERIMENTAL APPROACH: In vitro AT-090, UFP-113, and [F/G]N/OFQ(1-13)NH2 were tested for their ability to promote NOP/G-protein and NOP/ß-arrestin 2 interaction, using a bioluminescence resonance energy transfer assay. In vivo, they were tested in mice in the elevated plus maze (EPM) and in the forced swim (FST) tests. NOP partial agonists effects were systematically compared to those of full agonists (N/OFQ and Ro 65-6570) and antagonists (UFP-101 and SB-612111). KEY RESULTS: In vitro, AT-090, UFP-113, and [F/G]N/OFQ(1-13)NH2 promoted NOP/G protein interaction, with maximal effects lower than those evoked by N/OFQ and Ro 65-6570. AT-090 behaved as a NOP partial agonist also in inducing ß-arrestin 2 recruitment, while UFP-113 and [F/G]N/OFQ(1-13)NH2 were inactive in this assay. In vivo, AT-090 induced anxiolytic-like effects in the EPM but was inactive in the FST. Opposite results were obtained with UFP-113 and [F/G]N/OFQ(1-13)NH2. CONCLUSIONS AND IMPLICATIONS: NOP ligands producing similar effects on NOP/G protein interaction (partial agonism) but showing different effects on ß-arrestin 2 recruitment (partial agonism vs antagonism) elicited different actions on anxiety and mood. These results suggest that the action of a NOP ligand on emotional states is better predicted based on its ß-arrestin 2 rather than G-protein efficacy.

CO2 Laser Glazing Treatment of a Veneering Porcelain: Effects on Porosity, Translucency, and Mechanical Properties.

This work tested CO2 laser as a glazing agent and investigated the effects of irradiation on the porosity, translucency, and mechanical properties of veneering porcelain. Sixty discs (diameter 3.5 × 2.0 mm) of veneering porcelain for Y-TZP frameworks (VM9, VITA Zahnfabrik) were sintered and had one of their faces mirror polished. The specimens were divided into six groups (n=10/group) according to surface treatment, as follows: no treatment-control; auto-glaze in furnace following manufacturer's instructions (G); and CO2 laser (45 or 50 W/cm(2)) applied for four or five minutes (L45/4, L45/5, L50/4, L50/5). Optical microscopy (Shimadzu, 100×) was conducted and the images were analyzed with Image J software for the determination of the following porosity parameters: area fraction, average size, and Feret diameter. The translucency parameter studied was masking ability, determined by color difference (ΔE) over black and white backgrounds (CM3370d, Konica Minolta). Microhardness and fracture toughness (indentation fracture) were measured with a Vickers indenter (HMV, Shimadzu). Contact atomic force microscopy (AFM) (50 × 50 µm(2), Nanoscope IIIA, Veeco) was performed at the center of one sample from each group, except in the case of L45/5. With regard to porosity and translucency parameters, auto-glazed and laser-irradiated specimens presented statistical similarity. The area fraction of the surface pores ranged between 2.4% and 5.4% for irradiated specimens. Group L50/5 presented higher microhardness when compared to the G group. The higher (1.1) and lower (0.8) values for fracture toughness (MPa.m(1/2)) were found in laser-irradiated groups (L50/4 and L45/4, respectively). AFM performed after laser treatment revealed changes in porcelain surface profile at a submicrometric scale, with the presence of elongated peaks and deep valleys.

Temporal evolution of ¹³7Cs⁺, K⁺ and Na⁺ in fruits of South American tropical species.

Concentrations of (137)Cs, K and Na in fruits of lemon (Citrus limon B.) and of K and Na in fruits of coconut (Cocos nucifera L.) trees were measured by both gamma spectrometry and neutron activation analysis, with the aim to understand the behaviour of monovalent inorganic cations in tropical plants as well as the plant ability to store these elements. Similar amounts of K(+) were incorporated by lemon and coconut trees during the growth and ripening processes of its fruits. The K concentration decreased exponentially during the growth of lemons and coconuts, ranging from 13 to 25 g kg(-1) dry weight. The incorporation of Na(+) differed considerably between the plant species studied. The Na concentration increased linearly during the lemon growth period (0.04 to 0.70 g kg(-1) d.w.) and decreased exponentially during the coconut growth period (1.4 to 0.5 g kg(-1) d.w.). Even though radiocaesium is not an essential element to plants, our results have shown that (137)Cs incorporation to vegetable tissues is positively correlated to K distribution within the studied tropical plant species, suggesting that the two elements might be assimilated in a similar way, going through the biological cycle together. A mathematical model was developed from the experimental data allowing simulating the incorporation process of monovalent inorganic cations by the fruits of such tropical species. The agreement between the theoretical approach and the experimental values is satisfactory along fruit development.

Angiotensin-II-induced reactive oxygen species along the SFO-PVN-RVLM pathway: implications in neurogenic hypertension

Neurogenic hypertension has been the subject of extensive research worldwide. This review is based on the premise that some forms of neurogenic hypertension are caused in part by the formation of angiotensin-II (Ang-II)-induced reactive oxygen species along the subfornical organ-paraventricular nucleus of the hypothalamus-rostral ventrolateral medulla pathway (SFO-PVN-RVLM pathway). We will discuss the recent contribution of our laboratory and others regarding the mechanisms by which neurons in the SFO (an important circumventricular organ) are activated by Ang-II, how the SFO communicates with two other important areas involved in sympathetic activity regulation (PVN and RVLM) and how Ang-II-induced reactive oxygen species participate along the SFO-PVN-RVLM pathway in the pathogenesis of neurogenic hypertension.

Angiotensin-II-induced reactive oxygen species along the SFO-PVN-RVLM pathway: implications in neurogenic hypertension.

Neurogenic hypertension has been the subject of extensive research worldwide. This review is based on the premise that some forms of neurogenic hypertension are caused in part by the formation of angiotensin-II (Ang-II)-induced reactive oxygen species along the subfornical organ-paraventricular nucleus of the hypothalamus-rostral ventrolateral medulla pathway (SFO-PVN-RVLM pathway). We will discuss the recent contribution of our laboratory and others regarding the mechanisms by which neurons in the SFO (an important circumventricular organ) are activated by Ang-II, how the SFO communicates with two other important areas involved in sympathetic activity regulation (PVN and RVLM) and how Ang-II-induced reactive oxygen species participate along the SFO-PVN-RVLM pathway in the pathogenesis of neurogenic hypertension.

Possibilidades terapêuticas e risco toxicológico de Jatropha gossypiifolia L: uma revisão narrativa / Therapeutic possibilities and toxicological risk of Jatropha gossypiifolia L: a narrative review

A espécie Jatropha gossypiifolia L. (Euphorbiaceae), popularmente conhecida como pião-roxo, entre tantos outros nomes, é um bom exemplo do tênue limiar que separa o efeito terapêutico do tóxico. Apesar de ser classicamente conhecida como planta tóxica possui usos na medicina popular. Alguns desses efeitos têm sido comprovados em estudos experimentais, como os de antimicrobiano, antineoplásico, cicatrizante e hipotensor, sendo possivelmente explicados pela presença de substâncias como alcalóides, terpenóides, flavonóides, lignanas e taninos. Esta revisão aborda aspectos importantes, com ênfase na toxicidade crônica dessa espécie, de modo a servir de fonte de informação aos interessados em avaliar a relação risco/benefício do uso terapêutico de Jatropha gossypiifolia L.

The species Jatropha gossypiifolia L. (Euphorbiaceae), popularly known as bellyache bush, among several other names, is an important example of the tenuous threshold that separates the therapeutic from the toxic effect. Although traditionally known as a toxic plant, it has been used in folk medicine. Some of its effects have been proved by experimental studies as antimicrobial, antineoplastic, healing and hypotensive, likely explained by the presence of substances such as alkaloids, terpenoids, flavonoids, lignans and tannins. This review deals with important aspects, focusing on the chronic toxicity of this species, in order to serve as an information source for those interested in evaluating the risk-benefit ratio of the therapeutic use of Jatropha gossypiifolia L.

Ex vivo lung perfusion: early report of Brazilian experience.

INTRODUCTION: Only about 15% of the potential candidates for lung donation are considered suitable for transplantation. A new method for ex vivo lung perfusion (EVLP) can be used to evaluate and recondition "marginal," nonacceptable lungs. We have herein described an initial experience with ex vivo perfusion of 8 donor lungs deemed nonacceptable. MATERIALS AND METHODS: After harvesting, the lungs were perfused ex vivo with Steen Solution, an extracellular matrix with high colloid osmotic pressure. A membrane oxygenator connected to the circuit received gas from a mixture of nitrogen and carbon dioxide, maintaining a normal mixed venous blood gas level in the perfusate. The lungs were gradually rewarmed, reperfused, and ventilated for evaluation through analyses of oxygenation capacity, pulmonary vascular resistance (PVR), lung compliance (LC), and biopsy. RESULTS: The arterial oxygen pressure (with inspired oxygen fraction of 100%) increased from a mean of 206 mm Hg in the organ donor at the referring hospital to a mean of 498 mm Hg during the ex vivo evaluation. After 1 hour of EVLP, PVR varied from 440-1454 dynes/sec/cm(5); LC was in the range of 26-90 mL/cmH(2)O. There was no histological deterioration after 10 hours of cold ischemia and 1 hour of EVLP. CONCLUSIONS: The ex vivo evaluation model can improve oxygenation capacity of "marginal" lungs rejected for transplantation. It has great potential to increase lung donor availability and, possibly, reduce time on the waiting list.

Endothelium-derived nitric oxide is involved in the hypotensive and vasorelaxant effects induced by discretamine in rats.

The aim of this study was to investigate the pharmacological effects of discretamine, an isoquinoline alkaloid isolated from Duguetia magnolioidea Maas, on the cardiovascular system, using a combined in vivo and in vitro approach. Blood pressure and heart rate measurements, as well as changes in isometric tension in rat superior mesenteric arterial rings, elicited by discretamine were recorded. In normotensive non-anaesthetized rats (n = 6), discretamine (0.01; 0.05; 0.1; 0.5; 1, 5 and 10 mg/kg i.v., randomly) injections produced hypotension (-5.2 +/- 1.7; -5.1 +/- 2.1; -7.7 +/- 2; -8.9 +/- 1.7; -9.6 +/- 2.2; -16.8 +/- 2.8 and -13.4 +/- 1.3 mmHg, respectively) accompanied by tachycardia (24.2 +/- 6.1; 36.8 +/- 11.3; 44.2 +/- 7.7; 45.9 +/- 6.4; 48.2 +/- 9.1; 72.1 +/- 14.5 and 64 +/- 17 bpm, respectively). Hypotensive and tachycardic responses were significantly attenuated after L-NAME (20 mg/kg, i.v.) administration. In isolated rat mesenteric artery rings, with endothelium intact, discretamine (10(-12) - 10(-5) M) induced concentration-dependent relaxation of the contractions induced by phenylephrine (10 microM) [pD2 = 6.8 +/- 0.1]. The effect of the discretamine on phenylephrine induced contractions was significantly attenuated after removal of the vascular endothelium [pD2 = 5.8 +/- 0.04]. Similar results were obtained after pre-treatment with L-NAME 100 microM [pD2 = 5.8 +/- 0.04], L-NAME 300 microM [pD2 = 5.9 +/- 0.06], Hydroxocobalamin 30 microM [pD2 = 5.8 +/- 0.06] or ODQ 10 microM [pD2 = 5.8 +/- 0.04]. In addition, in rabbit aorta endothelial cell line, discretamine significantly increased NO3- levels. These results suggest that the hypotensive effect induced by discretamine is probably due to a peripheral vasodilatation, at least, in part, due to the release of NO from vascular endothelium and consequent activation of soluble guanylyl cyclase (GC) in the vascular smooth muscle cells.

Pyogenic granuloma, peripheral giant cell granuloma and peripheral ossifying fibroma: retrospective analysis of 138 cases.

AIM: The present study examined retrospectively the clinical and radiographic characteristics of pyogenic granuloma (PG), peripheral giant cell granuloma (PGCG) and peripheral ossifying fibroma (POF), located in the gingiva and alveolar ridge. METHODS: Biopsy records of the Stomatology Service of São Lucas Hospital-PUCRS were reviewed between 1980 and 2006. The medical charts of patients with histopathologic diagnosis of PG, PGCG and POF were selected. The data obtained were evaluated by means of descriptive statistics, analysis of variance (ANOVA), and the chi-squared test (chi-squared), considering the 5% level of significance. RESULTS: Of the 138 cases analyzed, 57.2% corresponded to PG, 22.5% to PGCG and 20.3% to POF. PG and POF exhibited a predilection for females and PGCG for males. PG occurred in younger individuals and showed a greater tendency for bleeding (P=0.018). PG showed a greater frequency of reddish color (P<0.001), PGCG purplish (P<0.001) and POF pinkish (P<0.001). In the radiographic examination, the presence of radiopaque foci was greater in POF (P<0.001), and resorption of the subjacent alveolar bone was found more often in PGCG (P<0.001). POF exhibited a longer evolution. There was no difference in lesions with respect to local irritating factors, ulceration, size, site and recurrence. Pregnancy was a factor linked to PG. CONCLUSION: Despite the lesions investigated exhibit similar clinical characteristics, the present study demonstrated that aspects such as age of the patient and evolution, color, bleeding and radiographic characteristics can help in the differential diagnosis of these lesions.

Cardiovascular effects of Hyptis fruticosa essential oil in rats.

In non-anesthetized normotensive rats, Hyptis fruticosa essential oil (HFEO, 5, 10, 20 and 40 mg/kg; i.v.) induced hypotension associated with tachycardia. In intact and isolated rings of rat superior mesenteric artery (control), HFEO (1-1000 microg/ml, n=6, cumulatively) induced concentration-dependent relaxations of tonus induced by 10 microM phenylephrine (Phe) (pD(2)=2.6+/-0.27; E(max)=64+/-8.3%). In denuded endothelium pre-contracted rings with Phe or K(+)-depolarizing solution (80 mM), the concentration-response curves to HFEO were not shifted (pD(2)=2.3+/-0.25 and 2.3+/-0.28, respectively), but their maximal responses were significantly (P<0.05 vs control) increased (E(max)=122.3+/-18.2% and 92+/-3.6%, respectively). HFEO was also capable of antagonizing the concentration-response curves to CaCl(2) (3 microM-30 mM) in a dose-dependent manner.

Structure-activity relationship study of flavone compounds with anti-HIV-1 integrase activity: a density functional theory study.

Human immunodeficiency virus type-1 integrase (HIV-1 IN) is an essential enzyme for effective viral replication. Flavone compounds have been very much studied due to their activity during the inhibition process of HIV-1 IN. In this study, we employed density functional theory (DFT) using the B3LYP hybrid functional to calculate a set of molecular properties for 32 flavonoid compounds with anti-HIV-1 IN activity. The stepwise discriminant analysis (SDA), principal component analysis (PCA) and hierarchical cluster analysis (HCA) methods were employed to reduce dimensionality and investigate possible relationship between the calculated properties and the anti-HIV-1 IN activity. These analyses showed that the molecular hydrophobicity (ClogP), charge on atom 11 and electrophilic index (omega) are responsible for the separation between anti-HIV-1 IN active and inactive compounds.