Programa de Pós-Graduação em Ciências Farmacêuticas - PPGCF/ICS

URI Permanente desta comunidadehttps://repositorio.ufpa.br/handle/2011/2312

O Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF) vinculado ao Instituto de Ciências da Saúde (ICS) da Universidade Federal do Pará (UFPA) apresenta um auto-impacto de inserção regional uma vez que se trata do único PPGCF na Região Norte pelo grande potencial de utilização da biodiversidade na região amazônica. Além de favorecer a fixação e atração de profissionais qualificados na área de Ciências Farmacêuticas na Região Amazônica.

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Acesso aberto (Open Access)
Análise do remédio artesanal “tintura de pata-de-vaca” tendo a tintura de Bauhinia monandra Kurz como referência
(Universidade Federal do Pará, 2016-03-17) SILVA, Ana Paula Paiva da; SILVA, Marcos Valério Santos da; http://lattes.cnpq.br/0379783635000306; BARBOSA, Wagner Luiz Ramos; http://lattes.cnpq.br/1372405563294070
Diabetes mellitus is one of the various pathologies can be controlled with the use of medicinal plants, which exhibit hypoglycemic activity through different mechanisms. In Marudá, Marapanim-PA, the Women's Group "Erva Vida", produces and markets the "Tintura de pata-de-vaca" consumed by tourists and locals to treat diabetes. This remedy is prepared from leaves of Bauhinia monandra Kurz (pata-de-vaca). Different metabolic classes of plant already had a proven hypoglycemic action, for example flavonoids. Thus, the aim of this study was to characterize the handmade medicine through pharmacobotanic parameters pharmacognostic, phytochemicals and chromatographic in compararação with a tincture of Bauhinia monandra, for the presence of flavonoids. Both the preliminary phytochemical analysis, and the analysis by Thin Layer Chromatography, phenolic metabolites detected, possibly flavonoids in handmade medicine and hydroethanolic extract of plant species. In the analysis by HPLC, it revealed the presence of rutin in handmade medicine as well as in hydroethanolic extract of Bauhinia monandra.
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)
Atividade imunomoduladora e antioxidante da saliva do Aedes aegypti em modelo de sepse
(Universidade Federal do Pará, 2017-07-04) GOMES, Rafaelli de Souza; 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 focused in the interruption of the inflammatory response chain, provided by the pathogens. In this way, the Aedes Aegypti’s saliva presents immunomodulary features, with a potential pro inflammatory cytokine inhibition, as well as the presence of nitric oxide peptides activators. Therefore, it would be a great interest to search the saliva’s immunomodulator effect in animal model sepses. In this regards, mices were pre treated with Aedes aegypti saliva, and sepsis was induced by the cecal ligation and puncture. After 12 and 24 hours, the samples were collected, and evaluated the survival rate, bacteria level, leukocyte migration, and oxidative parameters (NO, EROs, MDA e TEAC). The saliva improved the animal prognostic, increasing the survival rate and weight. Furthermore, decreased the bacterial levels and increased the influx of monocytes. The saliva, in addition, presented antioxidant effects by reducing production of the reatives species, and increasing the antioxidant capacity, other than decrease the lipid peroxidation. Thus, the saliva was capable to inhibit damages caused by sepsis in animals in vivo, improving its prognostic.
Acesso aberto (Open Access)
Avaliação da adesão ao tratamento com alfadornase em pacientes com fibrose cística
(Universidade Federal do Pará, 2017) FEITOSA, Keith Brabo Tavares; MARTINS, Valéria de Carvalho; http://lattes.cnpq.br/1904927472781784; ANDRADE, Marcieni Ataíde de; http://lattes.cnpq.br/8514584872100128
Cystic Fibrosis is an inherited disease, clinically manifested by digestive and respiratory symptoms. The early diagnosis offers the possibility of a better therapeutic control of the disease’s symptoms in favor of the prognosis and contributing to increasing quality of life. The aim of this study was to demonstrate the patient's behavior towards the disease and to evaluate the adherence to the treatment with the alfadornase enzyme. A cross-sectional study was carried out using epidemiological data collected through direct interviews with patients and/or their caregivers and by medical records analysis. Morisky-Green and Batalla Martinez tests were employed in order to evaluate the patient’s adhesion and knowledge of the disease, respectively. In addition, the clinical profile was assayed by Shwachman-Kulczyki score. Fifty-one (51) patients with cystic fibrosis in treatment with alfadornase were recruited at the outpatient clinic of the Hospital Universitário João de Barros Barreto. At final, forty-seven (47) patients participated in the study. Most of the patients (53.2%) were under 18 years of age, male (56.6%) and were from countryside (40.4%). Patients with long term use of alfadornase (> 5 years) show possess greater adherence than the others with a shorter treatment period. The male sex was associated with higher adherence, as well as greater education level and family income. The Batalla Martinez test demonstrates that only 40.42% of patients had some knowledgement about their disease. Thus, the factors associated with low adherence were: use of more than five medications, low education and gender. On the other way, these results shows that adherence to the medication was associated with the best clinical score.
Acesso aberto (Open Access)
Avaliação da adesão ao tratamento preconizado para malária: determinação da primaquina em pacientes diagnosticados com Plasmodium vivax
(Universidade Federal do Pará, 2016-03-31) GONÇALVES FILHO, Wilson Vieira; VIEIRA, José Luiz Fernandes; http://lattes.cnpq.br/2739079559531098; ANDRADE, Marcieni Ataíde de; http://lattes.cnpq.br/8514584872100128
Malaria is a disease that threatens 50% of the world population living in endemic areas such as Africa, Asia and Latin America. Concerning malaria caused by Plasmodium vivax in Brazil, which treatment is based on primaquine and chloroquine, it is a major public health issue that hinders the development of the Amazon region and adherence to drug therapy is one of the main factors that influence the effectiveness of the drug. This study uses indirect methods assess treatment adherence, correlating it with plasma concentrations of primaquine and carboxyprimaquine. Thus, a cross-sectional observational controlled study was conducted with 27 patients in Anajás, Pará before (D0), during (D1) and after (D7) treatment using the antimalarials, followed by the assessment of the patients with questions based on Morisky-Green test at the end of the treatment. Higher prevalence of vivax malaria was observed in males (70.4%) and age group of 20-39 years (55.56%), Morisky-Green test indicated adherence of 75%, 15 out of 20 patients, with hit rates of 80%, 65%, 70% and 65% to the questions. Mean-value of primaquine concentration on D1 was 134.8 ng/mL, and 131.9 ng/mL on D7, values for carboxyprimaquine are 408 ng/ml and 529.4 ng/mL respectively. It is possible to observe a statistically significant difference in the carboxyprimaquine values between D1 and D7 in the acceding group defined by the Morisky-Green tests, showing that carboxyprimaquine accumulates in the body; therefore being more suitable for assessing adherence to treatment. Therefore, it is important to point out these concentrations of primaquine and carboxyprimaquine consist as the first determination study of drugs and metabolites found for the short-course treatment suggested by the Ministry of Health for vivax malaria in the Amazon region, supporting the studies of adherence surveys regarding antimalarials.
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 atividade esquistossomicida do lapachol e análogos
(Universidade Federal do Pará, 2018-06-29) COSTA, Erica Vanessa Souza; ENK, Martin Johannes; http://lattes.cnpq.br/1169309283832476; DOLABELA, Maria Fâni; http://lattes.cnpq.br/0458080121943649
Mansonic chistosomiasis is a worldwide parasitic disease caused by Schistosomamansoni and its treatment performed with praziquantelhas some adverse reactions. The search for new drugs to treatment of this disease is important and medicinal plants can contribute with promising new molecules, such as lapachol. The present study evaluated the schistosomicidal activity of lapachol and analogues. Lapachol was isolated from Handroanthusserratifolius by silica gel chromatography column using dichloromethane as mobile phase. This substance was treated with sulfuric acid, followed by distilled water and dichloromethaneto obtain β-lapachone. To obtain α-lapachone, lapachol was solubilized and glacial acetic acid and concentrated hydrochloric acid were added. In order to evaluate schistosomicidal activity in vitro, an experiment was carried out on adult worms of S. mansoni, and morphology, motility and mortality in optic microscopy were evaluated. The active substance was submitted to the lipid peroxidation test, Malondialdehyde Dosage (MDA) and Total Antioxidant Capacity (TEAC). In addition, the active substance was submitted to cell viability assay (MTT), using the gastric epithelial (MNP01) and gastric adenocarcinoma (ACP02)strains. The active sample was evaluatedin vivo in infected mice, where wormsmortality, oviposition decrease and damage caused by parasites in animals were evaluated. Also, a histological study of kidney and liver of infected mouse treated with β-lapachone was performed. Lapachol (yield = 2.9%) and α-lapachone (yield = 60%) were not promise as schistosomicide, with their inhibitory concentrations being 50% higher than 500μg/mL in adult worms, whereas β-lapachone(yield = 65%) was very promising against adult worms (IC50 <31.25mg/mL). Analyzes in optical microscopy showed that β-lapachone treated worms presented tremor back, curled body, and lack of movement, these alterations may be related to lipid peroxidation in parasite membrane. This compound has a low antioxidant capacity, low cytotoxicity for the MNP01 and ACP02 strains, and the selectivity index is higher than 10. In vivo study showed that β-lapachone did not reduce the number of eggs in the faeces, so it did not inhibit ovoposition, and there were not alterations in the recoveredwormsnumber, and microscopic analysis showed they had motility and their membrane was integrated. Histological studies showed there were no renal and hepatic changes. In synthesis, β- lapachoneis promising as an in vitroschistosomicide and this activity may be related to lipid peroxidation in parasite membrane. However, in vitro study did not observe this activity, pharmacokinetic factors may be influencing results divergence.
Acesso aberto (Open Access)
Avaliação da citotoxicidade e seletividade do extrato, frações e alcaloide de Geissospermum sericeum (Apocynaceae) em linhagens celulares ACP02, HepG2 e VERO
(Universidade Federal do Pará, 2017-08-07) BASTOS, Mírian Letícia Carmo; BAHIA, Marcelo de Oliveira; http://lattes.cnpq.br/3219037174956649; DOLABELA, Maria Fâni; http://lattes.cnpq.br/0458080121943649
This study evaluated the antitumor activity of G. sericeum in primary gastric adenocarcinoma (ACP02), the selectivity and the mechanism of cell death. The G. sericeum bark powder was submitted to the exhaustive maceration with ethanol, which he resultant solution was concentrated on rotaevaporator until residue. For the fractionation of G. sericeum extract was used the fractionation under reflux and acid-basic partition. The alkaloid fraction (FAGS) obtained from the acid-basic partition was submitted to the open chromatography column (OCC), using Sephadex LH – 20 as stationary fase and the methanol as mobile fase, resulting in the subfracion F6FAGS. This subfracion was submitted to semi-preparative high performance liquid chromatography (HPLC) and the indole alkaloid (F3F6FAGS) was isolated. The cytotoxicity and antitumor activity of the ethanol extract, its fractions and F3F6FAGS were assessed through cell viability assay with MTT ([3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide]) in tumor-cell lines: ACP02, hepatocellular carcinoma (HepG2) and normal VERO cells (African green monkey). The samples with inhibitory concentration (IC50) below 100 μg/mL were considered active for antitumor activity in ACP02. The samples with IC50 ≤ 100 μg/mL were considered cytotoxic for cell lines HepG2 and VERO. The selectivity index (SI) was obtained from the ratio between the CC50 and IC50 values and the samples were considered selective with SI higher than two, indicating that this activity is twice selective for tumor cells. The most selective samples were submitted to quantification of cell death with fluorescent dyes Hoechst 33342 (HO), Propionium Iodide (PI) and Fluorescein Diacetate (FDA) during 24 and 72 hours of exposure. All samples were active or moderately active for antitumor activity and exhibited moderate cytotoxic activity or were not cytotoxic. The FAGS and indole alkaloid had lower IC50 (FAGS = 18, 29 μg/mL e F3F6FAGS = 12, 06 μg/mL) bigger CC50 (FAGS-CC50 = 173, 3 μg/mL for VERO and 299,45 μg/mL for HepG2 and F3F6FAGS CC50 476 μg/mL for renal cells and CC50 503,5 μg/mL for hepatic cells) and were more selective (F3F6FAGS- SI = 39,4 for VERO and SI = 41,74 for HepG2 and FAGS- SI = 9,5 for VERO and SI = 16,37 for HepG2). The FAGS had greater apoptosis and necrosis in 24h and 48h with increased necrosis in the higher concentrations and with the increase of the exposure time. For alkaloid, apoptosis and necrosis were shown concentration and time-dependent, with a lower necrosis rate. These results suggest some selectivity of the F3F6FAGS alkaloid for gastric cancer. However, the bigger cytotoxicity and the lower selectivity of FAGS are probably related to the synergism of its alkaloids for apoptosis and necrosis.
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 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)
Concentrações plasmáticas de rifampicina em pacientes com tuberculose pulmonar
(Universidade Federal do Pará, 2017-12-01) BELEZA, Breno Kristoffer Uchôa; VIEIRA, José Luiz Fernandes; http://lattes.cnpq.br/2739079559531098
Tuberculosis is an infectious-contagious disease that is still considered a major public health problem worldwide. Brazil is one of the 22 countries in the world responsible for 80% of the cases of the disease, and the highest incidence rates are observed in the North, Southeast and Northeast regions. The standard treatment regimen is composed of rifampicin, isoniazid, pyrazinamide and ethambutol. The clinical outcome is associated with the blood concentrations of these drugs after the use of therapeutic doses, however, despite the high incidence of the Brazilian disease, the concentrations of these drugs have not been evaluated in these patients, which is relevant mainly for rifampicin, given the high variability of concentrations in biological fluids after therapy. Therefore, a prospective case study was carried out to determine the concentrations of rifampicin by high performance liquid chromatography in patients with active tuberculosis treated in the city of Belém. Fifty patients were included in the study, however, there was a loss of clinical follow-up of 20 patients (40%), whose main reason was the abandonment of treatment. The social and demographic aspects of the others indicate a higher occurrence of the disease in males, low education, residents in the metropolitan area of Belém and in the productive age group. Rifampicin concentrations in the two treatment phases ranged from 0.6 μg / ml to 0.73 μg / ml. There was no significant difference in blood drug concentrations between treatment phases, however, rifampicin levels were significantly higher in women.
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/ 0000-0003-4842-8762
Pulmonary 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.
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/ 0000-0003-4842-8762
Tuberculosis 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.
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/ 0000-0002-7824-0042
Medication 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.
Acesso aberto (Open Access)
Determinação das concentrações sanguíneas de pirazinamida em pacientes com tuberculose pulmonar
(Universidade Federal do Pará, 2018-04-26) LUCENA, Stefania de Medeiros Araújo; VIEIRA, José Luiz Fernandes; http://lattes.cnpq.br/2739079559531098
Tuberculosis is an important health problem in Brazil. The first-line treatment regimen adopted by the Ministry of Health for the treatment of the disease consists of rifampicin, isoniazid, pyrazinamide and ethambutol in the intensive phase (02 months), and rifampicin and isoniazid in the maintenance phase (04 months) of the treatment. The determination of the concentrations of these drugs in biological fluids is determinant to confirm the adequate exposure, besides helping to identify the causes of the multiresistance. In Brazil, the concentrations of these drugs have not yet been described in the course of treatment of the disease. Therefore, this study aims to determine the blood concentrations of pyrazinamide in patients with clinical and laboratory diagnosis of pulmonary tuberculosis, evaluating the influence of sex and hyperglycemia on the plasma levels of these drugs. For this, 54 adult patients of both sexes, diagnosed with active pulmonary tuberculosis, submitted to the first line treatment were included in the study, from which blood samples were collected before treatment (D0), at the end of the first month (D30) and at the end of the second month of treatment (D60). Patients' socio-demographic data were collected through a questionnaire. Pyrazinamide concentrations were determined by high performance liquid chromatography with ultraviolet detection and glycemia by conventional spectrophotometric method. Of the patients included in the study, 53% are male and 90% are between 19 and 59 years old. In addition, 37% completed only elementary education. Eight patients were excluded by noncompliance. The mean plasma concentration of pyrazinamide in pre-dose samples was 3.4 μg / mL and in the post-dose samples it was 72.5 μg / mL. These data point to adequate exposure of M. tuberculosis to the drug. Patients' sex did not influence plasma pyrazinamide concentrations. These results allow us to conclude that the doses of pyrazinamide used in tuberculosis patients caused by M. tuberculosis ensure effective therapeutic blood concentrations in post-dose samples, as well as the pre-dose concentrations were consistent with the pharmacokinetics of the drug. Finally, post-dose concentrations were significantly higher in patients with hyperglycemia.
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/ 0000-0002-6186-9581
Tissue 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.
Acesso aberto (Open Access)
Efeito protetor de antioxidantes na formação de metemoglobina induzida pelo metabólito dapsona-hidroxilamina in vitro
(Universidade Federal do Pará, 2017-07-11) VARELA, Everton Luiz Pompeu; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390
Dapsone used in leprosy therapy its metabolite dapsone-hydroxylamine are potent pro-oxidant agents that cause acquired methemoglobinemia. For the treatment of this disease is used as antidote the Methylene Blue, however in high doses this antidote becomes pro-oxidant. In this sense, antioxidant substances may be potential alternatives to methylene blue for the treatment of methemoglobinemia. In this study we investigated the effect of antioxidants Ebselen, N-acetylcysteine, R-lipoic acid and L-lipoic acid on oxidative damage induced by dapsone-hydroxylamine in human erythrocytes, in vitro. Our results demonstrated that pre-treatment with antioxidants Ebselen, N-acetylcysteine, R-lipoic acid and S-lipoic acid prevented the formation of methemoglobin, reduction of glutathione and lipid peroxidation induced by the metabolite dapsone-hydroxylamine in human erythrocytes, In vitro. These substances were able to increase the antioxidant capacity of the erythrocyte associated with increased concentration of glutathione. Thus, antioxidants acted to reduce the oxidation of hemoglobin and / or directly or indirectly impeded the action of the metabolite dapsone-hydroxylamine. Our results indicate that the antioxidants tested can protect erythrocytes against oxidative damage under experimental conditions, suggesting that antioxidants may serve as the most effective and safe antidote in the treatment of methemoglobinemia.
Acesso aberto (Open Access)
Efeito protetor do ácido alfa lipóico sobre a lesão hepática, induzida por dapsona em modelo animal
(Universidade Federal do Pará, 2018-07-06) SAKAI, Joni Tetsuo; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390
The liver is the main organ involved in the biotransformation of xenobiotics, with the ability to convert hydrophobic compounds into water soluble, more easily eliminated by the body. Dapsone (DDS) is part of the multidrug therapy (MDT) of leprosy treatment, its metabolite is related to the generation of free radicals in hematological and neural cells, being thus directly involved in the main adverse reactions caused by its use. Due to its conversion cycle, which involves the reaction with iron present in the liver, DDS also accumulates in the liver, remaining longer in this organ, thus favoring tissue damage, such as drug hepatitis. In this context, the objective of the present study was to evaluate the protective effect of Alpha Lipoic Acid (ALA) on the liver damage caused by DDS in mice, after treatment. In this study, treatment with dapsone induced hepatic damage, with increase of Aspartate aminotransferase and alkaline phosphatase, as well as oxidative stress, by increasing lipid peroxidation and decreasing both glutathione levels and total antioxidants. These processes may be associated with accumulation of hepatic iron in the body. Already post-treatment with the antioxidant Alpha Lipoic Acid, this was able to decrease the levels of Aspartate aminotransferase and Alkaline Phosphatase, reverse lipid peroxidation and raise levels of GSH and total antioxidants. In addition, ALA also inhibited the accumulation of hepatic iron induced by dapsone in mice. Our results indicate that the antioxidant tested has a therapeutic potential against hepatic damage caused by dapsone in patients with leprosy.