Dissertações em Ciências Farmacêuticas (Mestrado) - PPGCF/ICS
URI Permanente para esta coleçãohttps://repositorio.ufpa.br/handle/2011/2313
O Mestrado Acadêmico em Ciências Farmacêuticas teve início em 2005 e homologado pelo CNE e funciona no Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF) do Instituto de Ciências da Saúde (ICS) da Universidade Federal do Pará (UFPA).
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Item 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/6710783324317390Ouratea 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.Item 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/6710783324317390Sepsis 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.Item 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/ 0000-0001-7495-9837Several 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.Item 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/ 0000-0001-5875-695XWound 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.Item 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/1034534634988402The 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).Item 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/ 0000-0002-9120-1910The 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.Item 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/ 0000-0002-9457-2733Myeloproliferative 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.Item 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/ 0000-0002-3328-5650Sepsis 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.Item 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/4835820645258101Ethyl 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 depressionItem 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/ 0000-0002-9457-2733Objective: 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.Item Acesso aberto (Open Access) Concentrações sanguíneas de pirazinamida e ácido úrico em pacientes em tratamento para tuberculose(Universidade Federal do Pará, 2020-12-7) SOUSA, Alberto Camarão de; VIEIRA, José Luiz Fernandes; http://lattes.cnpq.br/2739079559531098; https://orcid.org/ 0000-0003-4842-8762Pulmonary tuberculosis is a relevant public health problem in Brazil, where despite the measures of prophylaxis used, there is a high number of cases.The treatment is carried out in two stages: the intensive one, when combined fixed-dose tablets composed of rifampicin, isoniazid, pyrazinamide and ethambutol are administered and the maintenance phase with the use of rifampicin and isoniazid. This is effective in most cases of the disease, however, adverse reactions contribute to non- adherence to treatment, which can lead to therapeutic failure. Pyrazinamide is considered the most hepatotoxic drug, and causes several adverse reactions, such as hyperuricemia, however, few studies have investigated this reaction, which is relevant, because when accompanied by pain symptoms it can lead to treatment abandonment. The aim of this study was to measure plasma concentrations of pyrazinamide, by liquid chromatography of high- performance, and measure the serum acid uric levels, by spectrophotometry, in 44 patients positive by clinical, laboratory, and imaging tests. The measurement assay was done at the end of the intensive treatment phase. Most of the patients were men, with low education and low monthly income. The median daily doses of pyrazinamide administered was 26.2 (22.9-29.7) mg/kg to male patients and 26.8 (23.2-30.8) mg/kg to female. Plasma concentrations of pyrazinamide was 42 (10- 168) µg/mL to men and 50.5 (10-110) µg/mL (P <0.05) in women. The median of plasma concentrations was higher than the minimum inhibitory concentration for sensitive strains of the bacillus. The proportions of patients with serum uric acid levels above the normal range were 75% to female and 44.4% to male, with median values of 7.6 mg/dL and 7.4 mg/dL, respectively. Patient’s weight was not considered as a predictor of plasma pyrazinamide concentrations. The plasma pyrazinamide concentrations and the administered dose, expressed in mg/kg, were not associated with serum uric acid levels. The results of the present study demonstrate that the doses of pyrazinamide provide plasma concentrations that ensure adequate exposure of the bacillus to the drug. Acid uric levels were increased in the patients of this study, probably caused by the metabolites of pyrazinamide.Item Acesso aberto (Open Access) Concentrações séricas de rifampicina e glicemia em pacientes com tuberculose pulmonar ativa(Universidade Federal do Pará, 2019-08-30) FONSECA, Adriana Aparecida Durães; VIEIRA, José Luiz Fernandes; http://lattes.cnpq.br/2739079559531098; https://orcid.org/ 0000-0003-4842-8762Tuberculosis is a chronic disease caused by Mycobacterium tuberculosis, is considered an important public health issue in Brazil with approximately 70 to 90 thousand cases reported each year. The rates of incidences of chronic comorbidities associated with obesity increased in the last years, and, consequently, the coexistence of tuberculosis and diabetes mellitus also increase. There is an interesting interaction between these chronic diseases, as diabetes mellitus alter the immune response to infection and the pharmacokinetics of anti-tuberculosis drugs, and tuberculosis difficult the glycemic control in patients with diabetes. The aim of the study was to investigate the influence of diabetes mellitus on the serum concentrations of rifampicin in a cohort of patients under treatment with anti-tuberculosis drugs. After fasting of 12 hours, the concentrations of rifampicin, blood glucose levels, and glycated hemoglobin levels were measured at 1h after the ingestion of 600 mg of rifampicin. A total of 49 patients were included in the study and allocated in the TB group (n=36) and TB-DM group (n=13). The dose administered of rifampicin was similar in both groups, with median values of 9,82mg/kg and 10,14mg/kg in TB and TB-DM groups. The median serum concentrations of rifampicin in the intensive phase of treatment were 6,83µg/ml e 2,2µg/ml and in the continuation, were 2,75µg/ml and 2,48µg/ml, in TB and TB-DM groups. Approximately 12,25% of study patients presented rifampicin serum levels above the recommended value (8µg/ml). The concentrations of rifampicin were similar in TB and TB-DM groups in both treatment phases, but TB group present significant high levels of the drug in the acute phase of treatment. Moreover, the concentrations of rifampicin did not correlate significantly with glucose levels and glycated hemoglobin levels in both groups. Diabetes Mellitus did not provoke significant changes in serum rifampicin concentrations, but the treatment phase had a significant impact on drug levels.Item Acesso aberto (Open Access) Conciliação medicamentosa e revisão da farmacoterapia em oncopediatria: ações efetivas para prevenção de erros(Universidade Federal do Pará, 2018-08-23) PENHA, Nathalia Santos da; SILVA, Marcos Valério Santos da; http://lattes.cnpq.br/0379783635000306; https://orcid.org/ 0000-0002-7824-0042Medication errors in oncopediatry affect the chemotherapy treatment of prolonging hospitalization time, aggravate adverse reactions and the results in the patient, and are not desirable for the child-juvenile patient. Being a public where they are tested the viruses are very limited, they compete with a Clinical Pharmacy, an identification and identification of medication errors that can occur during the prolonged chemotherapy treatment of inpatients. This study was carried out with the objective of clarifying the diagnosis of mental disorders in patients hospitalized at a reference hospital in oncopediatrics in the north and northeast regions. 87.5% were diagnosed with 65% of patients with stable outcome status and 35% resolved status. In addition, 236 drugs were reconciled, identifying 51% of discrepancies, 90% being unintentional and 100% acceptability of the data. Based on the data, it is possible that the proportion of drug reconciliation and review of drugs are important to prevent errors and promote capacity reduction during the chemotherapy treatment of the child with cancer.Item Acesso aberto (Open Access) Efeito de uma espécie do gênero Varronia sobre a viabilidade celular, atividade antimicrobiana, toxicidade dérmica aguda e o processo de cicatrização (in vitro e in vivo)(Universidade Federal do Pará, 2019-09-09) RIBERA, Paula Cardoso; FONTES JÚNIOR, Enéas de Andrade; http://lattes.cnpq.br/7056265073849866; https://orcid.org/ 0000-0002-6186-9581Tissue damage, particularly to the skin, results in damage to cell structures, layers, and lineages to the fullest extent. Under these conditions, wound healing is the physiological process responsible for tissue repair. Inflammation is an important stage in tissue repair and; therefore, a strong target for clinical studies. The species Varronia multispicata is popularly used for the treatment of bruises, with recently discovered anti-inflammatory and analgesic effects. The present work aimed to investigate the effect of aqueous extract of Varronia multispicata leaves (VAR01) on cell viability, antimicrobial analysis, dermal toxicity, and in vitro and in vivo healing. In the in vitro assays, there were evaluated the cell viability in BALB/c 3T3 murine fibroblasts, the antimicrobial action by the microdilution method for determination of minimum inhibitory concentration and petri dish culture technique for the minimum bactericidal concentration. Healing assays were performed in cultured fibroblast monolayers. For in vivo assays in the dermal toxicity test, female Wistar rats were used and divided into the following groups: saline, 100mg/ml, 200mg/ml, and 1000mg/ml of VAR01; as for healing evaluation, Mus musculus mice were used and divided into 4 groups: sham, negative control, treated (VAR01 10%), and positive control (Dersani®). V. multispicata kept the cells viable for 24h, with reduction of fibroblasts in the 48h period at a concentration of 500 µg/ml. It showed no antimicrobial activity, presented in vitro and in vivo injury contraction capacity, did not promote death or behavioral changes, did not cause changes in water and feed intake, weight gain, relative weight, and organ histological analysis, showed a reduction in alkaline phosphatase concentrations in the group treated with 100 mg/ml extract when compared as control group. It was also revealed a reduction in alanine aminotransferase levels in the 100 mg/ml extract-treated group when compared to the control group. However, a significant increase in TGP concentrations was found in the 200 mg/ml group when compared to the control group. While assessing the degree of irritation, VAR01 did not show an irritant profile when administered acutely topically. Therefore, the extract is safe and of low toxicity, promising in the process of tissue regeneration with possible modulation in the inflammatory pathway, being a stimulating result for the following steps of biological activity evaluation and elucidation of the healing process.Item Acesso aberto (Open Access) Efeito protetor de antioxidantes na metemoglobina e no dano em dna induzidos pela dapsona-hidroxilamina in vitro(Universidade Federal do Pará, 2016-06-21) GOMES, Antonio Rafael Quadros; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390Dapsone (DDS) is one of the drugs used in polychemotherapy of leprosy associated with rifampicin and clofazimine. Of these drugs, DDS is primarily responsible for adverse reactions, such as methemoglobinemia and hemolytic anemia. These reactions are related to the DDS metabolite, dapsone hydroxylamine (DDS-NOH). In an attempt to promote the reduction of toxic effects are studied alternative therapies with antioxidants. This work aimed to evaluate the protective effect of N-acetylcysteine (NAC), A. brasiliensis and Glutathione ethyl ester (GSH-EE) in methemoglobin (MetHb) and DNA damage induced by DDS-NOH in vitro , correlating to oxidative stress parameters. For this, suspensions of human erythrocytes to 50% were pre- and post-treated with NAC, A. brasiliensis and GSH-EE in different concentrations, being exposed groups DDS-NOH to induce the formation MetHb. It also assessed whether the activity of enzymes-SOD and CAT and GSH levels, TEAC and MDA. In leukocytes evaluated the induction of ROS intracellularly using DCFH-DA and the damage to DNA by comet assay. The results showed that the DDS-NOH metabolite was capable of inducing MetHb in vitro, this dose-dependent effect. Regarding the pre-treatment, all the antioxidants prevented MetHb formation induced by DDS-NOH, as well as post-treatment. For SOD, only the pre-treatment with NAC and A. brasiliensis reduced SOD activity. In the post-treatment, there was increased when treated with antioxidants. Pre-treatment with NAC and GSH-EE increased CAT activity, moreover A. brasiliensis reduced, as after treatment with antioxidants. As for GSH levels, pre-treatment with NAC and GSH increased A. brasiliensis, on the other hand, did not alter after treatment. Regarding TEAC did not change. With respect to oxidative damage in the pre-treatment A. brasiliensis and GSH-EE reduced MDA. In the post-treatment, there was an increase in group A. brasiliensis and reduced GSH-EE group. Only the NAC was shown to be effective in removing the intracellular ROS induced by DDS-NOH in leukocytes. While in erythrocytes, a NAC and A. brasiliensis were able to reduce this effect. In the study of the comet assay, the DDS-NOH was able to induce DNA damage in peripheral blood leukocytes, however this damage was reduced when treated with NAC and A. brasiliensis. It can be concluded from our data that the evaluated antioxidants have therapeutic potential in the prevention of MetHb and DNA damage induced by DDS-NOH in vitro, more effective NAC against these effects.Item Acesso aberto (Open Access) Efeitos citoprotetor e citotóxico de Annona glabra (Annonaceae)(Universidade Federal do Pará, 2016-10-03) SARMENTO, Rosana Moura; SILVA, Jaqueline Rodrigues da; http://lattes.cnpq.br/8336745480297714; DOLABELA, Maria Fâni; http://lattes.cnpq.br/0458080121943649The present study evaluated the cytotoxic and cytoprotective potential of ethanolic extract obtained from the shells of Annona glabra, its fractions and isolated substances. The powder obtained from A.glabra husks was subjected to maceration with ethanol for 7 days, and the solution was concentrated in a rotavaporator to residue. The ethanolic extract from A.glabra was partitioned between aqueous hexane: methanol (9: 1). The methanolic fraction was fractionated in chromatographic column using as Sephadex stationary phase and mobile phase the methanol. The cytotoxicity of the ethanolic extract and fractions was evaluated by the MTT cell viability assay ([3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide]). The extract, fractions and subfractions were submitted to thin layer chromatography (CCD) analysis, and pooled according to similar characteristics. The 50% cytotoxic concentration (IC 50) was determined by linear regression. Fractions of the extract with IC50 ≤ 30 μg / mL and isolated substance with IC50 ≤ 4 μg / mL are considered cytotoxic. Fractions with moderate to low cytotoxicity were submitted to the induction of apoptosis and DNA fragmentation by flow cytometry. Also, these samples were submitted to evaluation of oxidative stress by the TEAC and DPPH method. The extract of A. glabra (8.39% yield) was partitioned to give the methanolic fraction (yield 88.14%) and hexane fraction (yield 8.08%). Ethanolic extract, methanolic fraction and rutin showed low cytotoxicity (IC50 = 137.7, 139.4,> 200 μg / mL, respectively). Hexanic fraction and subfractions 17 and 19 showed moderate non-significant cytotoxicity (IC50 = 45.07, 53.45, 80.65 μg / mL, respectively). All the evaluated samples did not induce apoptosis cells, however, ethanolic extract, hexane fraction and rutin promoted changes in the cell morphology. However, hexanic fraction, subfractions 6 and 7 showed the ability to fragment DNA from cells. The fractionation of the ethanolic extract favored the cytotoxic potential, with the hexane fraction being the most promising, and the antioxidant capacity was also favored, with group 5 being the most promising. These results suggest that A. glabra samples have low cytotoxic potential, and the mechanism involved is not related to the induction of apoptosis, and the ethanolic extract contains substances with antioxidant capacity.Item Acesso aberto (Open Access) Efeitos do antioxidante tempol nas alterações bioquímicas e estruturais induzidas pela metaloproteinase de matriz 2 no coração(Universidade Federal do Pará, 2020-09-11) GONÇALVES, Pricila Rodrigues; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390; https://orcid.org/ 0000-0002-3328-5650; PRADO, Alejandro Ferraz do; http://lattes.cnpq.br/7016475842644161; https://orcid.org/ 0000-0001-7495-9837MMP-2 expression is elevated in many cardiovascular pathologies such as myocardial infarction and heart failure, where tissue remodeling and inflammatory responses are disturbed. Changes in ECM homeostasis can lead to cardiac dysfunction. The most analyzed MMPs in relation to cardiac dysfunction are MMP 2 and MMP-9. ROS inhibitors, as antioxidants, have been shown to reduce the expression of MMP-2 in vascular tissue. Thus, antioxidants with Tempol have great potential to act on these mechanisms. Therefore, we evaluated the activity and purity of rhMMP-2 using the zymogram and SDS-PAGE silver-stained method. The animals were divided into 4 treatment groups. Group 1: received 0.9% saline; group 2: Tempol 18 mg / kg / v.o; group 3: MMP-2 150 ng / kg / i.p; group 4: Tempol 18 mg / kg / v.o + MMP-2 150 ng / kg / i.p; for 4 weeks. At the end of the treatment, the heart was collected for quantification of collagen, quantification of ROS by fluorescence microscopy and immunofluorescence for TNFα and TGF-β. After the analysis, our results showed that rhMMP-2 was pure and active and that there was no difference in the average weight of the animals (P> 0.05). In the group treated withrhMMP-2 and Tempol, there was a decrease in the heart weight / body weight ratio, compared to the control group (P <0.05). Tempol was able to decrease collagen in the heart of animals treated with rhMMP 2. We also saw rhMMP-2 increased ROS in the heart, which was prevented by Tempol. RhMMP-2 also led to an increase in TNF-α and TGF-β in the heart, however TGF-β was reduced by Tempol. In conclusion, rhMMP-2 infusion increased cardiac ROS, which can lead to oxidative stress, with a consequent increase in TNF-α and TGF-β, which can result in a heart with a pro-fibrotic and inflammatory profile. However, Tempol was able to reduce interstitial collagen, inhibit the increase in ROS, TNF-α, TGF-β and increase catalase in the heart. Having Tempol, the potential to inhibit factors that lead to oxidative stress, inflammation and cardiac fibrosis.Item Acesso aberto (Open Access) Efeitos do quelante de ferro, a deferoxamina, sobre as alterações oxidativas e cognitivas induzidas pela dapsona, em modelo animal(Universidade Federal do Pará, 2020-11-17) MENDES, Paulo Fernando Santos; MAIA, Cristiane do Socorro Ferraz; http://lattes.cnpq.br/4835820645258101; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390; https://orcid.org/ 0000-0002-3328-5650Dapsone (DDS) is an antibiotic that works by inhibiting folate synthesis, showing good bacteriostatic action. However, it can lead to severe adverse events such as neurological disorders, methemoglobinemia and hemolysis. These hematological disorders lead to the alteration of iron homeostasis and thereby increase the formation of ROS that can lead to cellular and tissue damage. This change plays an important role in neurodegenerative diseases, whether as a causative and / or intensifying agent in these diseases. In this context, we used an iron chelator, deferoxamine (DFX), to evaluate its effects on the formation of ROS triggered by the increase in free iron induced by the use of DDS. For this, the alteration of iron homeostasis was induced in Swiss mice, using DDS, followed by the administration of DFX. After that, oxidative stress parameters were measured in the hippocampus and plasma, in addition to the measurement of iron levels. Our results showed that DDS decreased TEAC and that DFX treatment was restored. In addition, DDS decreased GSH and DFX treatment was restored. It increased the LPO and the treatment with DFX reduced this effect, increased the concentration of iron and that was reversed by the treatment with DFX. Additionally, the animals were submitted to the Morris water maze, where our results showed that animals treated with DDS showed a reduction in mnemonic capacity and that treatment with DFX was able to inhibit loss. These results suggest that the use of iron chelators may be an alternative to reduce the effects of iron accumulation on the nervous system observed in neurodegenerative diseases.Item Acesso aberto (Open Access) Estudos farmacognósticos, fitoquímicos e atividade antileishmania de espécies Geissospermum (Apocynaceae)(Universidade Federal do Pará, 2016-11-07) SILVA, João Victor da Silva e; MARINHO, Andrey Moacir do Rosario; http://lattes.cnpq.br/2511998363000599; DOLABELA, Maria Fâni; http://lattes.cnpq.br/0458080121943649This study aimed to perform pharmacognostic and phytochemical studies, and assess antileishmanial activity and cytotoxicity of Geissospermum vellosii Allemão and Geissospermum sericeum Miers. The pharmacognostic study was carried out as described in the Brazilian Pharmacopoeia, 2010. The ethanol extracts (GVEE and GSEE) were obtained by exhaustive maceration with ethanol (96 ° GL), followed by concentration in rotaevaporator. The ethanol extract was fractionated using two methods: extraction under reflux (fractions of different polarities) and acid-base partition (neutral and alkaloid fractions). The alkaloid fractions (GVAF and GSAF) were fractionated on a chromatographic column with Sephadex LH-20 gel, and the resulting subfractions were analyzed on TLC, and reveled through Dragendorff reagent and ultraviolet (365 nm). The F6GVAF and F6GSAF subfractions, with alkaloids detected and good yield, were subjected to semi-preparative HPLC-DAD, and spectrophotometric methods. For evaluating the antileishmanial activity, promastigote forms of Leishmania amazonensis at a concentration of 5 x 106 parasites/100μL were treated with the samples at different concentrations for 24, 48 and 72h. The analysis was done adding [3- (4,5-dimethylthiazol-2-yl) -2,5- diphenyltetrazolium bromide (MTT) to the samples in an ELISA reader at 490 nm. Cytotoxicity was assessed through cell viability assay with MTT in differentiated THP- 1 cells and HepG2. As a selection criteria, the selectivity index (IS) was calculated as the ratio between the cytotoxic concentration 50% in cell lines, and the inhibitory concentration 50% found for protozoa, considering as promising values ≥ 10. The plant powder was classified as thick (G. vellosii), and very thick (G. sericeum), low density, with pH 4.94 (G. vellosii) and 6.47 (G. sericeum), negative to saponins, with ash and moisture within the parameters established by the Brazilian Pharmacopoeia V. In the phytochemical study, we suggest the isolation of an indole alkaloid (F3F6FAGV) and a β-carbolinic (flavopereirine) from both species. The fractionation of GVEE and GSEE resulted in more cytotoxic subfractions, but the exposure time and refractionation reduced this effect. In the antipromatigota assay, all samples were active, and the fractionation increased the activity. The flavopereirine presented time-dependent activity greater than amphotericin B. However, the flavopereirine in association with indole alkaloid and/or amphotericin B reduced the selectivity of this metabolite. The extracts fractionation increases the selectivity index, and the selectivity of flavopereirin is high (SI = 4893.3). Therefore, the isolation of flavopereirine contributes to reduce cytotoxicity and increase selectivity, showing itself as a promising antileishmanial agent.Item Acesso aberto (Open Access) Estudos farmacognósticos, fitoquímicos e biológicos de Annona glabra L. (Annonaceae)(Universidade Federal do Pará, 2016-05-12) BRÍGIDO, Heliton Patrick Cordovil; MARINHO, Moacir do Rosario Marinho; http://lattes.cnpq.br/2511998363000599; DOLABELA, Maria Fâni; http://lattes.cnpq.br/0458080121943649In this study, the Annona glabra underwent pharmacognostic, phytochemicals and biological studies (leishmanicide and antimicrobial activity). In pharmacognostic studies, we used the methods described in Brazilian Pharmacopoeia V ed. (2010). The ethanolic extract (EE) was obtained by maceration of the powder batch of shells with ethanol. The extract was fractionated by liquid-liquid partition with hexane and 10% aqueous methanol resulting in hexane (HF), and methanol (MF) fractions. The MF was submitted to Sephadex column. This procedure resulted in 46 fractions that were analyzed in thin layer chromatography and revealed with sulfuric acid, Dragendorff, and ultraviolet (360 nm) being assembled into 5 groups according to their chromatographic profiles. Group 3 was purified by column chromatography on a preparative scale yielding the G3-1 sample. EE, MF, HF, Group 2 and G3-1 were analyzed by HPLC-DAD. The G3-1 sample was analysed by mass spectrometry and nuclear magnetic resonance (NMR). To evaluate the antimicrobial activity, methods of agar diffusion (Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa) and microdilution (MIC) were used. The EE and its fractions were subjected to leishmanicide activity test (Leishmania amazonensis). The powder was classified as coarse and low-density, with ash and moisture contents within the parameters established by the Brazilian Pharmacopoeia. In HPLC-DAD, the main peaks of EE and its fractions were presented in UV absorption spectrum of 240 nm to 280 nm, and 300 nm to 400 nm suggestive respectively Band II (Ring A), and band I (ring B ) of flavonoid. The G3-1 chemical structure was identified as flavonoid rutin. In the agar diffusion test, we observed the formation of halos in EE and MF only in Staphylococcus aureus plates. In the microdilution assay, the EE and FM showed MIC> 1000 mg / mL, considered inactive. In antileishman test, the EE showed IC50> 200 / ml. The MF and HF also showed IC50> 200 / ml; however, they inhibited the growth of promastigotes respectively in 20% and 33.7%. The subtractions and G3-1 Group 2 showed IC50> 200 / ml, but the concentration of 200 / ml inhibited the parasite growth by approximately 45%. The EE, fractions, and subfractions were inactive against L. amazonensis amastigotes. However, the HF concentrations of 250 and 125 g / ml inhibited infection in 39.1% and 18.7%. In short, EE and its fractions were shown to be inactive in the antimicrobial and leishmanicide trials, but fractionation contributed to increase activity suggesting that active substances must be at low levels in extract and its fractions.