Navegando por CNPq "CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA"

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Acesso aberto (Open Access)
Ação da hidroxicloroquina sobre neurônios da retina de embrião de galinha
(Universidade Federal do Pará, 2017-03-22) ROSÁRIO, Aldanete Santos; NASCIMENTO, José Luiz Martins do; http://lattes.cnpq.br/7216249286784978
Hydroxychloroquine (HCQ) is currently used in the treatment of malaria and autoimmune diseases and others therapeutic purposes. However, this drug is known to cause side effects, including producing visual disturbances, which may be irreversible. The mechanisms that produce these visual disorders are not completely known. HCQ - related retinal toxicity may be due to high metabolic rate, being very susceptible to the action of xenobiotics and oxidative damages. Thus, this work aims to evaluate the effects of the HCQ on retinal cells, as well as their possible mechanisms of cytotoxicity. The model used in this work was of cultures of retina cells from chicken embryo. To evaluate cell viability, mitochondrial activity was measured by MTT. The lysosomal function was evaluated by the incorporation rate of the neutral red dye. The levels of reactive species of general oxygen and superoxide anion were evaluated by the CellROX probe and by Nitro Blue Tetrazolium (NBT) and total glutathione levels were quantified using the Ellman reagent. Viability was tested in mixed cultures (glia and neurons) or enriched cultures of neurons and glia after treatment with HCQ and compared with chloroquine (CQ). Cells were exposed to concentrations of 25μM, 50μM and 75μM for 24 hours. The results show that mixed cultures treated with CQ presented a reduction in viability of 36 and 61% at concentrations of 50μM and 75μM, respectively, whereas HCQ did not alter viability at any of the concentrations tested. However, when cultures enriched with glial cells were exposed to HCQ for 24 hours, the concentration of 75μM had a small reduction in cell viability, while that the reduction in neuronal cells was of 20, 33 and 56% at the concentrations of 25μM, 50μM and 75μM, respectively. Even a shorter treatment time (6 hours) there was loss of viability in retinal neurons. The incorporation of neutral red supravital dye was also altered in neuronal cultures treated with HCQ for 24 hours, with reduction of 19 and 32%, compared to the control for the concentrations of 50μM and 75μM, respectively. HCQ significantly reduced the levels of reactive oxygen species produced by the neuronal cells, mainly superoxide anion, 43, 52 and 61% for the concentrations of 25μM, 50μM and 75μM of HCQ in 24 hours of treatment, respectively. In concentrations of 50μM and 75μM of HCQ for 24 for hours, the levels of total glutathione in neuronal cells presented a reduction of 37 and 53%, respectively. When the glial cell conditioned medium was used in neuronal cells for 6 hours after treatment with HCQ, it completely reversed the drug-induced cytotoxicity. When total glutathione levels were measured in culture of glia treated with HCQ for 24 hours no changes were observed. These results suggest cytotoxic action of CQ in mixed culture of chicken embryo retina cells which is not observed in HCQ treatment. However, HCQ showed cytotoxic action when cells are cultured separately, mainly on neurons, which is reversed by some factor released by glial cells in the extracellular environment, and glutathione is a possible candidate to exert this neuroprotective function.
Acesso aberto (Open Access)
Análise morfológica in vitro da ação de antifúngicos em cepas de Fonsecaea pedrosoi
(Universidade Federal do Pará, 2014-02-21) MASSOUD JUNIOR, Heleno Ramos; SALGADO, Claudio Guedes; http://lattes.cnpq.br/2310734509396125
Choromoblastomycosis (CBM) is a disease caused by traumatic implantation of many species of melanized fungi. The State of Pará is the major endemic area in Brazil and Fonsecaea pedrosoi is the major etiological agent. The treatment is not standardized and many forms of interventions are related in the literature. In the other hand, the in vitro susceptibility test to antifungal drugs may help in the therapeutic choice and in the identification of resistant strains. The objective of this work is to evaluate the in vitro susceptibility of 20 F. pedrosoi clinical isolates to itraconazole (ITZ), ketoconazole (KCZ), fluconazole (FCZ) and terbinafine (TBF) as well as the possible morphological alterations induced by ITZ or TBF in the Minimal Inhibitory Concentration (MIC) and high concentrations. The tests were performed according to the Clinical and Laboratory Standards Institute (CLSI, M38-A2 document) recommendations. The final concentrations of ITZ, TBF and KCZ in each test were to 16 to 0.03 μg/mL. To FCZ the final concentrations were to 64 to 0.125 μg/mL. The MIC was defined as the lowest drug concentration that inhibit 100% the visual growth when compared to the non-treated group after five days of incubation at 30°C. ITZ proved to be the most effective drug in vitro against F. pedrosoi (CIM 90= 1μg/mL). TBF showed a low drug activity with 70% of the isolates with MIC ≥ 0.5 μg/mL. The conidia morphological analysis revealed an increasing in the diameter, an interruption of the cellular division and the formation of little chains after the treatment with ITZ in the MIC. At the high concentration used in the susceptibility test we noticed an irregular shape, a detachment of pigmented material from the cell wall and a vacuolization. Rupture in cell wall and amorphous conidia were observed at 32 μg/mL and 64 μg/mL. Significant alterations were not observed after treatment with TBF at the same concentrations. Moreover, the 5-fluorocytocise (5-FC) and FCZ do not stop the conidia growth at high concentrations. However, ultrastructure alterations were noticed after treatment with 5-FC 64 μg/mL. Thus, it is suggested a different morphological pattern after ITZ or TBF treatment during the in vitro susceptibility test. In synthesis, ITZ shown better in vitro antifungal activity while 5-FC only provoked structures alterations in the highest concentration tested.
Acesso aberto (Open Access)
Apoptose de células inflamatórias e evolução clínica do Eritema Nodoso Hansênico: ensaio com Azatioprina
(Universidade Federal do Pará, 2008) OLIVEIRA, Miguel Saraty de; XAVIER, Marília Brasil; http://lattes.cnpq.br/0548879430701901
Leprosy is a chronic infectious and contagious disease, affecting mainly skin and peripheral nerves, interrupted by outbreaks reaction, classified as Type I or reverse reaction and the reaction type II or erythema nodosum leprosum, usually accompanied by neuritis.Thalidomide and prednisone are widely used in treat ENL, but are not always fully effective, it needs to be investigate other immunosuppressive drugs to control the reaction. The phenomenon of apoptosis of inflammatory cells occurs in leprosy and ENL, but few studies correlating the phenomenon with clinical improvement or worsening of the ENL reaction are available. This report describes the occurrence of apoptosis of inflammatory cells and clinical progression of erythema nodosum leprosum before, during and after the use of azathioprine to treat ENL. The results obtained with 07 patients enrolled in the study indicate that the drug, azathioprine, is effective in treating cases of ENL difficult to treat. This drug may induce remission of ENL, as well as to further decrease the dose of prednisone in use.The phenomenon of apoptosis could be documented using the immunogold with caspase 3 in all cases. There was no significant variation seen between the number of cells highlighted with caspase 3 before and after treatment with azatioprina.No significant correlation between the number of cells highlighted with caspase 3 before and after treatment with azathioprine and clinical improvement shown could be demonstrated.
Acesso aberto (Open Access)
Atividade antibacteriana, antioxidante e citotóxica in vitro do extrato etanólico da entrecasca da planta Ouratea hexasperma (EEEOH) (A. St-Hil.) Baill var. Planchonii Engl
(Universidade Federal do Pará, 2015-09-17) COSTA, Glauber Vilhena da; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390
Ouratea hexasperma (Ochnacea), popularly known as "cerrado barbatimão" is a very common plant in the brazilian cerrado region and has been used for the treatment of microbial infections and inflammation. Therefore, this study aimed to evaluate the antioxidant activities, quantifying total flavonoid content (TFT), antibacterial and cytotoxicity of ethanol extract of the bark of Ouratea hexasperma (EEBOH) as well as perform their phytochemical characterization. The plant was collected in the state of Amapá, and then was held extraction of dry bark through the cold maceration with 96% ethanol solution in a 2: 8 (w/v) for 1 day, forming the EEBOH. The phytochemical characterization was performed by testing chromatic/precipitation tube and flavonoid content was measured by assay complexation with aluminum using quercetin as standard (40-0,62μg/mL), and the total antioxidant capacity by the spectrophotometric method discoloration radical ABTS•+ (2,2'azino-bis-3-etilbenzotiazolin 6-sulfonic acid) - TEAC. The antimicrobial activity of EEBOH was tested against gram-positive and gram-negative bacteria, using the microdilution techniques broth with staining by resazurin, to determine the Minimum Inhibitory Concentration (MIC), and grown in petri dish with subsequent count of colony forming units (CFU) for obtaining the Minimum Bactericidal Concentration (MBC). The evaluation of the cytotoxicity of EEEOH human peripheral blood leukocytes. Mononuclear peripheral blood cells incubated with different concentrations of the extract and without stimulation (negative control). The cytotoxicity of EEEOH were tested using human peripheral blood leukocyte, mononuclear cells, with different extract concentrations and without stimulation (negative control), and incubated and maintained at 37 ° C, 98% humidity and 5% CO2 for 24 hours, NO and MDA were read in an ELISA spectrophotometer and different optical readings. The primary EEBOH phytochemical analysis showed the presence of tannins, saponins and flavonoids. The TFT in the extract was 1467 ± 264μg equivalents quercetin/g EEBOH. The antioxidant capacity by TEAC method showed high antioxidant activity, with no difference in antioxidant capacity (TEAC) between those concentrations of the extract. The EEBOH showed good antibacterial activity, mainly against gram-positive bacteria. The cytotoxicity was obtained by linear regression concentration able to kill 50% of cells (CC 50%) whose amount was 2231,5mg/mL, confirming that the crude extract has low cytotoxicity against human leukocytes, under the conditions tested. In the production of NO and MDA it found that the EEOC was not able to induce NO production of the concentrations tested. As well, no increase MDA of concentration induces changes when compared to the negative control (RPMI), confirming the low in vitro cytotoxicity of the extract. Statistical analyzes were performed by ANOVA one way and Turkey. In concluded that the EEBOH have antibacterial, antioxidant and low cytotoxicity.
Acesso aberto (Open Access)
Atividade antiinflamatória e neuroprotetora da Edaravona no córtex sensóriomotor primário de ratos adultos submetidos à isquemia focal experimental
(Universidade Federal do Pará, 2014-02-12) ARAÚJO, Sanderson Corrêa; BORGES, Rosivaldo dos Santos; http://lattes.cnpq.br/4783661132100859; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072
Stroke is a neural disorder originated from blood flow decreasing or interruption, making inadequate energy supply in the region, thus promoting tissue damage. The stroke can be divided in hemorragic or ischemic. The ischemic stroke is more prevalent and can occur through thrombosis or embolism. The ischemic pathology has multiple interrelated events like excitotoxicity, peri-infarct depolarization, oxidative and nitrosative stress, inflammation and apoptosis. An element of fundamental importance in ischemic pathology is the microglial cell, whose activity is closely linked to the progression of environment harm. A therapeutic alternative in the treatment of stroke is a pyrazolone called Edaravone. This study evaluated the neuroprotective effect of Edaravone dose of 3mg/kg in primary sensorymotor cortex after focal ischemic lesion. Edaravone treated animals (N = 10) and animals treated with saline solution (N = 10) in the survival time of 1 and 7 days after the ischemic event was evaluated. Treatment whith edaravone showed by histopathological analysis with cresyl violet a reduction of 49% and 66% in infarct size in animals in survival time 1 and 7 days respectively. Immunohistochemistry studies for microglia/macrophages assets (ED1+) demonstrated a reduction in the presence of ED1+ cells in 35% and 41% survival times for 1 and 7 days, respectively. Neutrophils (MBS-1+) were reduced to 64% only in animals with survival times a day. Harmful patterns were assessed qualitatively and quantitatively. Data was tested by ANOVA with Tukey post hoc test. Differences were considered significant at p < 0,05.
Acesso aberto (Open Access)
Atividade antimicrobiana, antioxidante e imunomoduladora de Agaricus brasiliensis e Ilex paraguariensis in vitro e em modelo de sepse murino
(Universidade Federal do Pará, 2016-09-15) NAVEGANTES, Kely Campos; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390
Sepsis is an organ dysfunction caused by a dysregulated immune response to an infection, the initial therapeutic approach to sepsis are broad spectrum antimicrobials, which is not sufficient for control of infection, requiring association with other therapies. Thus, Ilex paraguariensis where to be a potent antimicrobial, antioxidant and Agaricus brasiliensis has immunomodulatory properties could be a new source of therapy. Thus, this study aimed to evaluate the antimicrobial effect, antioxidant and immunomodulatory in vitro and in vivo of the extracts. Therefore, in this study, we evaluated the in vitro antimicrobial activity of aqueous extracts from A.brasiliensis and I. paraguariensis against Staphylococcus aureus and Escherichia coli by the method of microdilution and by spectophotometry for determination of minimum inhibitory concentration and cultivation technique on petri dish for minimum bactericidal concentration, cytotoxicity in macrophages was evaluated, nitric oxide (NO) production, proliferation, phagocytosis, equivalent antioxidant capacity to Trolox (TEAC) and determination of the total antioxidant activity by capturing the free radical and reactive species production oxygen (ROS). In the swiss mice with induced sepsis were pretreated with aqueous extracts of A.brasiliensis and I. paraguariensis, after 12 and 24 hours collected their samples and evaluated the survival, leukocyte migration, hemogram, bacterial load, NO production, malondialdehyde (MDA), TEAC and ex vivo we evaluated phagocytic capacity and release of ROS. The A.brasiliensis showed no antimicrobial activity in vitro, remained viable cells reduced the phagocytic capacity, increased NO, but in the presence of LPS reduced, showed proliferative effect, but in the presence of mitogen had antiproliferative effect and has a strong antioxidant activity and capacity to sequester radicals in vitro. I.paraguariensis presented antimicrobial activity as well as cytotoxic effect induced phagocytic capacity increased NO, but in the presence of LPS reduced, had proliferative effect, antioxidant activity and capacity to sequester radicals in vitro. In vivo model of sepsis, both increased the survival of animals, A.brasiliensis reduced leukocyte influx while Ilex increased, only A.brasiliensis had hemogram similar to sham, both extracts reduced bacterial load and levels decreased NO, MDA and increased antioxidant levels in the tissues, in addition, both reduced the production of both extracts present ERO. Although excellent in vitro results, the aqueous extract from A.brasiliensis was found to be most promising as an adjuvant therapy in sepsis that I. paraguariensis due to its high antimicrobial activity, antioxidant and anti-inflammatory in vivo.
Acesso aberto (Open Access)
Atividade antiproliferativa e antineoplásica de flavonóides da espécie Brosimum acutifolium em modelo de glioblastoma in vitro
(Universidade Federal do Pará, 2013-05-24) MAUÉS, Luis Antônio Loureiro; NASCIMENTO, José Luiz Martins do; http://lattes.cnpq.br/7216249286784978
Among the tumors that affect the nervous system, glioblastoma multiforme (GBM) is notable by its high degree of aggressiveness and poor prognosis, with an average survival of 15 months from diagnosis. The present study aimed to investigate the antiproliferative and antineoplastic activity of four flavonoids isolated from species Brosimum acutifolium (Huber). two flavans: 4'-hydroxy-7,8-(2",2"-dimethylpyran)-flavan (BAS-1) and 7,4'-dihydroxy-8-(3,3-dimethylallyl)-flavan (BAS-4), and two chalcones: 4,2'-dihydroxy-3',4'-(2",2"-dimetilpirano)-chalcone (BAS-6) and 4,2',4'-trihydroxy-3'-(3,3-dimethylallyl)-chalcone (BAS-7), tested on rat C6 glioblastoma in vitro. Our results showed good cytotoxic activity for flavans (BAS-1, -4) and the chalcone BAS-7, with IC50 less than 100 μM in the MTT viability test, since the chalcone BAS-6, showed no cytotoxicity at the concentrations tested. These flavonoids showed less cytotoxity for non-neoplastic cell (glia), with higher degree of security for the BAS and BAS-4-7, once showed lower cytotoxic effect on non-neoplastic cell, and less hemolytic. Analysis of cell migration showed that treatment with BAS-1; -4 and -7 at low concentrations was effective in promoting the inhibition of cell migration. These three flavonoids were also very promising in inhibiting colony formation and growth, and promote cell cycle arrest with a substantial increase in population SubG0 for treatment with BAS-1 and -4 with 100 μM. The flavans BAS-1 and -4 also showed increased ability to promote losing in the integrity of the mitochondrial membrane potential (ΔΨm) and increased for staining with Annexin V, indicating that these drugs cause death by apoptosis. However the analysis by electron microscopy showed markedly the presence of autophagic vacuoles in the treatment with BAS-4 suggesting that the process of cell death occurs by apoptosis as well as autophagy. Based on these results it can be concluded that the flavonoids BAS-1, -4, and -7 have potential as an anticancer agent in the therapy of GBM and BAS-4 is the most promising of all.
Acesso aberto (Open Access)
Atividade antitumoral em células de câncer gástrico e atividade antioxidante de extratos de Eugenia patrisii vahl
(Universidade Federal do Pará, 2020-09-09) REIS, Herald Souza dos; AMARANTE, Cristine Bastos do; http://lattes.cnpq.br/4101983776191966; https://orcid.org/ 0000-0002-8602-8180; PRADO, Alejandro Ferraz do; http://lattes.cnpq.br/7016475842644161; https://orcid.org/ 0000-0001-7495-9837
Several antineoplastic drugs are natural origin or from derived compounds and plants are one of the primary sources of substances for this sort of drugs. Studies with Myrtaceae family plants, demonstrated several effects such as anticancer and antioxidant. A plant in this family that may have biological activities is Eugenia patrisii Vahl, popularly known as Ubaia-rubi-da-amazônia, a plant native to the Amazon Region. Therefore, the work objective was to evaluate the antitumor and antioxidant activity of hydroalcoholic extracts of the leaf and stem of the E. patrisii species. The chemical profile of the extracts was done using thin layer chromatography. The antioxidant activity was assessed by the DPPH test. For antitumor activity, a cell viability test was performed using the MTT method on gastric cancer lines (ACP02, ACP03 and AGP01) and normal lines (VERO and MN01). Gel zymography was also performed to assess the activity of MMP-2 and MMP-9. The data obtained were analyzed using the Graph Pad Prism program version 8.0. The tests used were variance analysis (ANOVA) and Test t Student, with p <0.05 being considered significant. The plates derived from thin layer chromatography showed presence of terpenes, flavonoids, phenolic compounds and absence of coumarins and alkaloids. The extracts were shown to have antioxidant capacity through the DPPH assay. In the cell viability test, the extracts showed a high potency against gastric tumor lines and did not affect the normal line. In addition, the leaf extract decreased MMP-2 and MMP-9 activity in gel. The extracts have terpenes, flavonoids and phenolic compounds that have an antioxidant activity of 82% compared to the standard and antitumor against gastric lines ACP03 and AGP01 with the potential to isolate compounds of pharmacological interest.
Acesso aberto (Open Access)
Avaliação da atividade antinociceptiva e anti-inflamatória da Pellucidina A e elucidação do mecanismo de ação em modelos in vivo
(Universidade Federal do Pará, 2016-10-13) QUEIROZ, Amanda Pâmela dos Santos; MAIA, Cristiane do Socorro Ferraz; http://lattes.cnpq.br/4835820645258101; BASTOS, Gilmara de Nazareth Tavares; http://lattes.cnpq.br/2487879058181806
The Peperomia pellucida (Piperaceae) is an herbaceous plant commonly found in the American and Asian continents. In the Amazon the species is known by the name of erva-de-jabuti. This plant is used in folk medicine to treat a wide range of symptoms and diseases such as conjunctivitis, headache, asthma, gastric ulcer, inflammation and arthritis. Pellucidin A is an isolated compound of the species Peperomia pellucida and this study aimed to analyze the antinociceptive and anti-inflammatory activity of this compound, as well as to elucidate its mechanism of action. For the assays, male albino mice (25-40 g) were used, which were initially treated with pellucidin A at the doses of 0.5; 1 and 5 mg / kg (i.p.) and subjected to locomotor evaluation by the open field test and animal models of acute pain, such as acetic acid-induced abdominal writhing tests, formalin tests and the hot plate test. The acetic acid-induced abdominal contortion test was realized to elucidate the mechanism of action in which the animals were treated at the standard dose of 5 mg/kg (i.p.) and for anti-inflammatory analysis of the compound was used model of granuloma induced by pellets of cotton, in which the animals were treated in the dose of 10 mg/kg (i.p.). The compound did not show capacity to change the ambulation of the animals at any of the administered doses. In the contortion test, pellucidin A was able to inhibit the number of abdominal writhings in 43% at the dose of 1 mg/kg, and 65% at the dose of 5 mg/kg. In the formalin test, an antinociceptive effect was observed at the dose of 5 mg/kg, with a 68% reduction in the lymph time of the animal's paw in the inflammatory phase, showing a similar response to Indomethacin used at a dose of 10 mg/kg as positive control for this phase. Animals treated with pellucidin A and subjected to the hot plate assay did not show any change in their latency time on the plate, showing a similar response to the animals treated just with the vehicle solution. For the elucidation of the action mechanism, the pellucidin A was administered at the standard dose of 5 mg/kg (i.p.) and associated with Indomethacin (5 mg/kg i.p.), NS-398 (10 mg/kg i.p.) cyproeptadine (0.5 mg/kg i.p.), naloxone (1 mg/kg i.p.) and L-NAME (5 mg/kg i.p.). The pellucidin A has shown a synergistic action when associated with cyproeptadine and L-NAME, with a decrease in the pattern of abdominal writhing by 97% when associated with cyproheptadine and 96% with L-NAME. In the analysis of the action of pellucidin A (10 mg/kg i.p.) in the granuloma test induced by cotton pellets, pellucidin A presented anti-inflammatory activity, reduced granuloma formation in 24% in the treated mice. The results confirm the hypothesis that pellucin A presents analgesic activity capable of interfering in the inflammatory process, acting as a possible glucocorticoid agonist.
Acesso aberto (Open Access)
Avaliação da atividade cicatrizante do extrato hidroalcoólico de Ayapana triplinervis (Vahl) R.M. King & H. Robinson (ASTERACEAE)
(Universidade Federal do Pará, 2020-07-16) NASCIMENTO, Suellen Carolina Martins do; LIMA, Anderson Bentes de; http://lattes.cnpq.br/3455183793812931; https://orcid.org/ 0000-0002-0534-2654; ANDRADE, Marcieni Ataíde de; http://lattes.cnpq.br/8514584872100128; https://orcid.org/ 0000-0001-5875-695X
Wound healing is a complex process that involves the organization of cells, chemical signals and remodeling in order to repair injured tissue. North American statistical data show a prevalence of skin lesions in approximately 22.8% of the world's population. In Brazil, wounds are a serious public health problem. In this sense, the use of medicinal plants as therapeutic agents has aroused interest among researchers due to their most different effects, including healing. Thus, ethnopharmacological studies are found in the literature, which associate the use of A. triplinervis with wound healing, but there is no scientific evidence to prove this activity. Thus, this study aims to evaluate the healing potential of the hydroalcoholic extract of A. triplinervis incorporated in an ointment of 5 and 10%. For that, phytochemical analyzes were carried out: prospecting of the plant drug and the hydroalcoholic extract, by means of colorimetric, precipitation tests, thin layer chromatography and high-performance liquid chromatography of the hydroalcoholic extract. In addition to the macroscopic, morphometric analysis, and histological examination of the hydroalcoholic extract ointment in 5% and 10%, using Dersani® and saline solution, respectively, as positive and negative controls. Through these tests, it was observed that the plant drug presented several compounds: saponins, anthraquinones, steroids and triterpenes, polyphenols and coumarins. For the hydroalcoholic extract the result was similar, but the tests did not indicate the presence of anthraquinones. Analysis by thin layer chromatography of the hydroalcoholic extract revealed positive results for coumarins, steroids and triterpenes. In the chromatographic profile, the extract, obtained by high performance liquid chromatography, showed a peak, being suggestive of coumarin. Macroscopic analysis of the lesions showed that the groups of the 5% and 10% extract ointments had more re-epithelialized wounds. In morphometry there was no statistical difference between the four test groups in the percentage of wound contraction. However, the histological examination showed that the ointment with 10% hydroalcoholic extract showed better quality in the development of tissue repair, as it increased fibroblasts, collagen, keratinization, more than the other groups. Thus, this study showed that A. triplinervis extract ointment did not accelerate the speed of wound closure, however, it did show a beneficial influence on the quality in which the lesions evolved, yet further research is necessary to better understand It is made.
Acesso aberto (Open Access)
Avaliação da composição química e atividades biológicas dos óleos essenciais de Lippia gracilis e Lippia origanoides da Amazônia oriental
(Universidade Federal do Pará, 2012-10-17) FRANCO, Caroline da Silva; SILVA, Joyce Kelly do Rosário da; http://lattes.cnpq.br/2278686174214080; MAIA, José Guilherme Soares; http://lattes.cnpq.br/1034534634988402
The genus Lippia is known for its aromatic character and medicinal use of its species as an alternative therapy. Essential oils of Lippia gracilis and L. origanoides collected in Pará and Maranhão were obtained by hydrodistillation and were rich in monoterpenes. The major compounds oil of L. gracilis were thymol (72.5%), p-cymene (9.3%) and thymol methyl ether (5.4%); for oil of L. origanoides were thymol (45.8%), p-cymene (14.3%), -terpinene (10.5%) and carvacrol (9.9%). The oils had potential larvicide against Artemia salina with LC50 values of 7.4 ± 0,2 μg.mL-1 to L. origanoides and 18.7 ± 0.2 μg.mL-1 to L. gracilis, both more active than lapachol (EC50 = 21.2 ± 2.2 μg/ ml). The essential oil of L. gracilis showed moderate scavenging capacity DPPH with EC50 value = 35.7 ± 3.32 μg.mL-1 about 8 times less active than the standard trolox (EC50 of 4.5 ± 0.1). Furthermore, the oil L. gracilis proved to be a good natural fungicide against the phytopathogen C. sphaerospermum with limit of detection of 5 μg, about 10 times less active than miconazole (DL = 0.5 μg). Moreover, the oil L. origanoides no showed significant activity (DL = 100μg).
Acesso aberto (Open Access)
Avaliação da influência do tratamento com indometacina no aprendizado e na memória espacial em modelo murino de diabetes tipo 1
(Universidade Federal do Pará, 2017-05-25) SANTOS, Gabriel Cardoso de Queiroz; BASTOS, Gilmara de Nazareth Tavares; http://lattes.cnpq.br/2487879058181806
Diabetes mellitus (DM) is the group of metabolic disorders that has as a common characteristic the disregulation of blood glucose levels, invariably leading to hyperglycemia. This disease has become the most frequent in the adult population, mainly in developing countries, causing several serious consequences such as cardiovascular and renal diseases, factors responsible for a high mortality rate of the individuals affected. In addition that consequences, which are better investigated and described in the literature, other types of complications are observed. Clinical and experimental studies demonstrate that both type 1 and type 2 diabetes mellitus may contribute to the development of cognitive deficits and dementias. However, the mechanisms that lead to such disorders are not yet fully understood. A study using the non-selective non-steroidal anti-inflammatory, indomethacin, has shown that aspects related to impaired neuronal plasticity in diabetes can be reversed, demonstrating that these disorders may be modulated by neuroinflammatory changes. The aim of the present study was to evaluate the influence of chronic treatment with indomethacin on memory and learning in a murine model of type 1 diabetes mellitus (T1DM). Using the open field test, Y-maze test and Morris water maze test we investigated the indomethacin effects on behaviors changes after aloxan inducing T1DM. Indomethacin significantly decrease related behaviors to the anxious state in Open field test. This treatment also reversed space work memory deficits in the Y-maze test, and learning and spatial memory deficits in the Morris Water Maze. Thus, it can be concluded that chronic treatment with indomethacin has beneficial effects on the cognition of mice submitted to type 1 diabetes mellitus.
Acesso aberto (Open Access)
Avaliação de atividade antimicrobiana e perfil fitoquimíco de plantas medicinais utilizadas por comunidades remanescentes de quilombos no Marajó
(Universidade Federal do Pará, 2020-12-28) SILVA, Suzana Helena Campelo Nogueira da; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390; https://orcid.org/ 0000-0002-3328-5650; SILVA, Consuelo Yumiko Yoshioka e; http://lattes.cnpq.br/8337688339279747; https://orcid.org/ 0000-0002-9120-1910
The ethnopharmacological survey is recognized as one of the most viable methods in the search for new medicinal plants, with the ultimate purpose of producing medicines of natural or semi-synthetic origin. In this sense, the remaining communities of Amazonian quilombolas (Marajó-PA) carry with them a great deal of knowledge about the use of medicinal plants, which has been passed down for generations in Mararajo soil, promoting the value of popular knowledge and its applicability in future studies. The objective of this study is to provide scientific support for the traditional use of plants in the treatment of dermatological diseases in quilombola communities in Marajó that do not yet have an adequate chemical and / or pharmacological study. During the fieldwork carried out between 2017 and 2018, 13 communities were interviewed, in which 7 plants with use in skin diseases were cited. Such plants were collected, and their exsiccates were prepared. After botanical identification by a qualified professional, an extensive bibliographic review was carried out, after which 3 plants were selected for phytochemical and pharmacological study (in vitro in Microsporum and Staphylococcus aureus). In addition, they were subjected to ORAC antioxidant and TP total polyphenols tests. The phytochemical profile was analyzed using liquid chromatography coupled to mass spectrometry (LC-MS) providing 17 chemical constituents, belonging to the flavonoid class. The results of the in vitro tests showed an antibacterial potential of the ethanolic extract of the leaves of C. alatus (MIC) of 0.625 µg / mL and (CBM) of 0.734 µg / mL and of the ethanol extract of the roots D. floribunda (MIC) of 125, 0 ug / mL and 200.0 μg / mL (CBM) compared to S. aureus, with emphasis on the F3 fraction (MIC) 25.0 μg / mL and (CBM) of 132.0 which presented the highest bacterial inhibition. Therefore, the results contributed to the validation of popular use and chemical characterization of the species that presented antimicrobial potential, which can be a promising candidate for herbal medicine.
Acesso aberto (Open Access)
Avaliação de neutrófilos circulantes em pacientes com neoplasias mieloproliferativas philadelphia negativas em tratamento quimioterápico
(Universidade Federal do Pará, 2018-06-27) SARGES, Érica dos Santos; RIBEIRO, Carolina Heitmann Mares Azevedo; http://lattes.cnpq.br/3848996822163999; https://orcid.org/ 0000-0002-9457-2733
Myeloproliferative neoplasms (MPNs) are a group of blood cell diseases that arise from a change in the hematopoietic stem cell. The most classic are Polycythemia vera (PV) and Essential thrombocythemia (ET). Negative Ph1 NMPs have a long and relatively benign clinical course but have no cure. Cytoreductive chemotherapy acts not only on erythrocytes and megakaryocytes, but also has its action on leukocytes, specifically neutrophils. One of the therapies employed is Hydroxyurea (HU), which has neutropenia as one of its side effects, studies show that this drug can have direct effects on neutrophils. The identification of possible quantitatively and qualitatively changes of neutrophils under the effects of cytoreductive chemotherapy in patients with negative Ph1 MPNs represents an advance in the understanding of the treatment in these MPNs. Hemogram and leukogram are part of the treatment follow-up protocol. In order to qualitatively evaluate some functions, the neutrophils were sensitized with zymosan, thus stimulating the phagocytosis, in relation to the metabolism, the cytochemical test of spontaneous reduction of nitroblue tetrazolium (NBT), besides quantification of myeloperoxidase (MPO) through flow cytometry. In this study, all methodologies previously cited for quantitative and qualitative evaluation were performed on blood samples from 46 patients (PV = 17; ET = 29). The patients with PV had lower IF than the control group, with p = 0.0002 (2.83 ± 1.28, 3.83 ± 1.38, respectively). The same was observed in the patients with ET who presented lower index than the control subjects with p = 0.0002 (2.85 ± 1.34, 3.83 ± 1.38 respectively). Our results showed that there was no difference in the activation of the oxidative metabolism in the NBT reduction test, between the control group and the PV group in HU use, with p = 0.9047 (5 ± 2.7, 2.9 ± 3.5 respectively) and control group with ET group in HU use, presenting p = 0.2870 (5 ± 2.7, 5 ± 6.9 respectively). The MPO test was performed on all patients with NMPs who were undergoing treatment with HU. Our results showed that there was no difference between the control group and the patients in the PV group, with p = 0.8438 (98.47 ± 1.15, 98.54 ± 1.46, respectively). controls and patients with ET, with p = 0.5842 (98.47 ± 1.15, 97.93 ± 3.21 respectively). Patients with PV and ET who used HU presented qualitative changes in neutrophils, in which the use of HU decreased the phagocytic activity of neutrophils in these patients.
Acesso aberto (Open Access)
Avaliação do efeito imunomodulador da β-lapachona em modelo de sepse e in vitro
(Universidade Federal do Pará, 2018-06-29) OLIVEIRA, Ana Lígia de Brito; BRAGA, Alaide; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390; https://orcid.org/ 0000-0002-3328-5650
Sepsis is a systemic inflammatory response resulting from an infection and failure of the host immune response. Despite the current treatments, sepsis remains one of the main causes of death in ICU. Thus, it is necessary to discover new therapies developed to control the infection. Β-lapachone is an ortho-naphthoquinone obtained from the bark of Tabebuia avellanedae known for its antimicrobial and anti-inflammatory activity through immunomodulation. In this study, the effect of β-lapachone on polymicrobial infection induced by ligature and cecal perforation (CLP) was evaluated. Swiss mice were divided into 4 pre and post treated groups, and one of them only received the surgical procedure without induction of CLP (Sham). The others received intraperitoneal saline 0.9%, antibiotic (Ceftriaxone or ertapenem) and β-lapachone 24 hours before, induction time (Pretreatment) of CLP and 7 days after CLP (Post treatment). The survival rate was analyzed for a period of 16 days. After 12, 24 hours and 7 days of the surgical procedure the samples of the animals of each group were collected and evaluated the leukocyte migration, bacterial load, oxidative parameters (NO, MDA and TEAC) and phagocytosis. In addition, the cell viability of the compound in different concentrations was investigated in vitro. The group pretreated with β lapachone showed an increase in the survival rate of 100% in 16 days. Treatment with β-lapachone caused an increase in the migration of mononuclear cells and reduced the number of neutrophils to the peritoneum. It also showed reduced bacterial load, reduced NO and MDA levels and increased serum antioxidant levels. On the other hand, there was an increase in the concentrations of MDA in samples of animal organs despite the increase of total antioxidants. With regard to posttreatment, there was an increase in survival of 60% and some parameters similar to the CLP group treated with saline. In the cell viability assay it was found that the concentration of 1.00 μM maintained 82% viable. Thus, the best results of the potential pharmacological effect of the compound on pretreatment may have occurred because the therapeutic intervention occurs earlier in the disease process compared to the clinical situation.
Acesso aberto (Open Access)
Avaliação do efeito neuroprotetor da cafeína em ratas intoxicadas por etanol no padrão binge
(Universidade Federal do Pará, 2019-05-03) BARROS, Mayara Arouck; FERNANDES, Luanna de Melo Pereira; http://lattes.cnpq.br/0156144290849777; https://orcid.org/0000-0001-7004-0719; MAIA, Cristiane do Socorro Ferraz; http://lattes.cnpq.br/4835820645258101
Ethyl alcohol is a substance consumed since the dawn of mankind, extending to the present day. In this context, adolescents are attracting attention because consumption in this group is constantly rising, especially in the Binge Drinking pattern. This model of consumption leads to functional impairments, such as symptoms associated with anxiety and depression. For this reason, has been sought bioactive compound to prevent such damages, among them we can highlight the caffeine, substance widely consumed in the world. In view of this, this paper aims to investigate the neuroprotective effect of caffeine in self administration on the damages caused by EtOH intoxication in the binge pattern, aiming at an alternative to minimize the neurotoxic damages promoted by alcohol with the simple habit of drinking coffee. For this, Wistar rats, females, age 35 days (n = 40) were used. At treatment, animals received caffeine repeatedly from the 35th to the 72nd postnatal day (PND). Caffeine was administered as a 0.3g / L caffeinated solution in self-administration in the active period, starting 14 days before the first day of ethanol intoxication and persisting during the 4 weeks of BD. For ethanol intoxication in the binge pattern, it was administered by gavage at a dose of 3 g / kg / day (20 w / v) for three consecutive days weekly in the animals from the 49th to the 72nd PND. For behavioral tests, the animals were exposed to Open Field, Elevated-plus-maze, Splash and Forced swimming test. In relation to the anxious type behavior, the Caffeine + EtOH Group showed a significant increase in the distance and time traveled in the central area in the Open Field Test when compared to the EtOH group. In the LCE Test, the EtOH group showed reduction in %EBA and %TBA when compared to the control group. However, the caffeine group showed reversion when increasing both parameters when compared to the EtOH group. In the depressive-type behavior, the EtOH-intoxicated group presented reduction of the grooming time and increased immobility time, in the Splash and Forced Swim tests, respectively. The EtOH + Caffeine group was able to increase grooming time in the first test and reduce immobility time in the second. Thus, we can conclude that chronic consumption of caffeine promoted neuroprotection by reversing symptoms similar to anxiety and depression
Acesso aberto (Open Access)
Avaliação do polimorfismo INDEL no gene TYMS em associação a resposta quanto ao uso de fluoropirimidinas em pacientes portadores de neoplasias do trato gastrointestinal
(Universidade Federal do Pará, 2014-02-26) COSTA, Danielle Feio da; SANTOS, Ney Pereira Carneiro dos; http://lattes.cnpq.br/1290427033107137
Cancer is a public health problem worldwide, with an estimated of 27 million new cases and 17 million cancer deaths in 2030. In Brazil, estimates for cancer in 2014, indicate the occurrence of approximately 580 000 new cases. Fluoropyrimidines are used in the main chemotherapy regimens targeted to tumors of the gastrointestinal tract. Recently, much has been investigated on causes of different individual responses to chemotherapy.Thus, it has been sought an individualized therapy that can maximize drug efficacy and minimize adverse effects associated with drugs. We aimed to seek the association of an INDEL polymorphism (rs16430) in TYMS gene with the pattern of response to chemotherapy drugs based on fluoropyrimidines, in order to contribute to the development of personalized medicine. We studied 151 samples of cancer patients treated with fluoropyrimidine, from a population of the Brazilian Amazon region with high interethnic admixture. An INDEL polymorphism (rs16430) was genotyped in TYMS gene that is involved in the response to treatment using fluoropyrimidines. The research reported that most patients had advanced disease at diagnosis, of which 32.7% were treated with palliative intent, and 22.8% neoadjuvant treatment. Our results show that the INDEL polymorphism in the TYMS gene appears to have a protective effect on tumor progression (p = 0.033). Patients treated with fluoropyrimidine who were wild homozygous (INS / INS) had a 24% protection to tumor progression compared to other genotypes of this polymorphism. Estimates of global genetic ancestry of the sample investigated were: 62.4% European, 25.2% Amerindian and 12.4% African. It was possible to establish an inverse correlation between the increase of Amerindian ancestry and metastasis (p = 0.024). Pharmacogenetic studies can provide a personalized therapy toxicity reducing mortality and improving therapeutic efficacy, thereby providing a cancer therapy with better clinical results.
Acesso aberto (Open Access)
Avaliação funcional de neutrófilos circulantes em portadores de leucemia mielóide crônica antes e após o início do tratamento com mesilato de imatinibe
(Universidade Federal do Pará, 2019-07-02) DAMASCENO, David Wendell Isacksson; RIBEIRO, Carolina Heitmann Mares Azevedo; http://lattes.cnpq.br/3848996822163999; https://orcid.org/ 0000-0002-9457-2733
Objective: To evaluate neutrophil function in patients with chronic myeloid leukemia (CML) before and after initiation of treatment with imatinib mesylate (MI). Material and Methods: The study included 13 patients diagnosed with CML (new cases), with a mean age of 51 years, of both sexes, selected at the hematology outpatient clinic of the Ophir Loyola Hospital, Belém-PA. In this group three blood samples were taken. The first collection at the time of diagnosis with the untreated patient (Group B1), the second collection after one month of IM treatment (Group B2) and the third collection after four months of treatment (Group B3). The control group (Group A) consisted of 13 healthy volunteers of both sexes. In addition to the blood count and leukogram, the phagocytosis assays and the cytochemical test for spontaneous reduction of nitroazul tetrazolium (NBT) were also performed to evaluate the neutrophil oxidative metabolism. Results: The evaluation of phagocytic function indicated statistical difference when compared Group A with Groups B1, B2 and B3, p = 0.0001. Groups B1, B2 and B3 presented lower phagocytic indices (IFs) with 2.07 ± 0.5; 1.99 ± 0.4 and 1.97 ± 0.6 respectively, compared to Group A with 3.72 ± 0.8. In the oxidative metabolism evaluation there was no statistical difference between group A with groups B1, B2 and B3, p = 0.2997. Discussion: The results showed that untreated patients had lower IF compared to the control group. This means that even if the patient has innumerable cells of the proliferative process, these cells have their functions diminished. Patients treated with MI also had lower IF compared to the control group. Although the number of leukocytes and neutrophils decreased in these patients, the phagocytic capacity of these cells remained decreased. There was no statistical difference regarding the activation of oxidative metabolism in the NBT reduction test. This means that the production of ROS by the NADPH oxidase system does not change independently of MI treatment. Conclusion: There was a reduction in the amount of circulating neutrophils after initiation of IM treatment. The phagocytic function of neutrophils remained decreased after initiation of IM treatment. Neutrophil oxidative metabolism does not change independently of MI treatment. Therefore, additional studies are important to evaluate the exact mechanism of function alteration involved in these patients to allow a better orientation regarding the therapy used.
Acesso aberto (Open Access)
Avaliação in vitro dos efeitos de miltefosina, orizalina e TC95 no crescimento de Entamoeba histolytica
(Universidade Federal do Pará, 2011) ALVARENGA, Betânia Mara; BATISTA, Evander de Jesus Oliveira; http://lattes.cnpq.br/2206444845201080
Amebiasis is characterized as a chronic, noninflammatory, afebrile which involves the colon wall and can invade the intestinal mucosa and spread to other organs, especially the liver. Entamoeba histolytica infection is treated with metronidazole, but this one presents side effects, so researches have been done to find more effective drugs with no adverse effects to the patient. In addition, testing new drugs may reveal important features of the parasite, such as the discovery of metabolic pathways or possible differences in their structure. In the present study, it was tested the amoebicidal effect of metronidazole, dinitroaniline oryzalin, a microtubule inhibitor, miltefosine, an alkylphosphocholine, that inhibits the membrane phospholipids syntesis, and TC95, a hybrid drug that presents the functional groups dinitroaniline and alkylphosphocholine. It was performed a culture with protozoan trophozoites, where the drugs and the control with diluents were added after 7 hours of culture. It was made a count of the viable trophozoites 12 hours after the addition of the drugs and the control at intervals of 12 to 60 hours. After analyzing the growth curves, it was found that the TC95 was the most effective drug of the three treatments, miltefosine had little inhibition and oryzalin was not effective. This is due to greater susceptibility of the parasite to membrane damage, with little effectiveness on microtubules inhibition.
Acesso aberto (Open Access)
Avaliação pré-clínica da duloxetina em modelo de convulsão: análise comportamental, eletroencefalográfica e influência no estresse oxidativo
(Universidade Federal do Pará, 2014-06-17) COELHO, Danielle Santana; CRESPO LÓPEZ, Maria Elena; http://lattes.cnpq.br/9900144256348265
Epilepsy is a disorder with high prevalence and severity. Although there are several anticonvulsant drugs available in the market, 30 to 40% of the patients are refractory to the treatment. Besides the seriousness of epilepsy per se, this disorder may be accompanied by many comorbidities such as depression, which is the main psychiatric comorbidity of epilepsy. The mechanisms involved in the relationship between epilepsy and depression are not clarified. Given that some anticonvulsant drugs can trigger or enhance depressive symptoms, while some antidepressant drugs can potentiate the severity of seizure, the concomitant treatments of both disorders can be problematic. On the other hand, some studies have shown that antidepressant drugs can be safe and even possess an anticonvulsant activity such as venlafaxine, a serotonin and noradrenaline reuptake inhibitor (SNRI). Considering that duloxetine, another SNRI, has a more potent inhibition of monoaminergic transporters and that there is no study about its influence on seizures, the aim of our study is to verify the potential anticonvulsant action of duloxetine against seizures induced by pentylenetetrazole (PTZ) on mice. With this aim, mice will be pre-treated with duloxetine (10, 20, 40 mg/kg/i.p.), and thirty minutes after, the animals will receive an intraperitoneal injection of PTZ (60 mg/kg, i.p.). In the following twenty minutes the animals are going to be evaluated. The threshold for the first myoclonic jerk, tonic-clonic seizure, the duration of seizures and survival will be quantified. The electroencephalographic analysis (EEG) was used to assess the severity of the seizures (wave’s amplitude increase). After this period the animals will be sacrificed, the cerebral cortex dissected and biochemical analysis (activity of superoxide dismutase (SOD), catalase (CAT), nitrite levels and lipid peroxidation) will be made to investigate the mechanisms by which this drug can influence seizures. The results exhibit the anticonvulsant action of duloxetine. The drug was capable of enhancing the threshold for the first myoclonic and tonic-clonic seizures induced by PTZ. Additionally, the EEG demonstrated that duloxetine at the dose of 20 mg/kg decreased significantly the amplitude of the waves while at the dose of 40 mg/kg it increased the amplitude when compared to all the treatments. Regarding the evaluation of duloxetine’s influence on oxidative stress, all the animals treated solely with PTZ presented a significant increase on lipid peroxidation and a decrease on SOD and CAT activity. Concerning nitrites’ level, there was no difference between the treatments. The dose of 20 mg/kg of duloxetine showed a significant protection against the alterations in oxidative stress induced by PTZ. The anticonvulsant action of duloxetine (20 mg/kg) collaborates with the theory which has been presented in the last few years where it is proposed that the modulation of the serotonergic and noradrenergic neurotransmission may exert an anticonvulsant activity. Moreover, the efficiency of duloxetine in preventing the aggravation of oxidative stress involved in the seizures induced by PTZ corroborates with studies that demonstrate that anticonvulsant substances can influence seizures through its antioxidant activity. Given these points, we conclude that duloxetine is a promising adjuvant for the treatment of patients with the comorbidity epilepsy and depression.