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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Diagnóstico situacional e análise espacial da logística reversa de medicamentos domiciliares vencidos ou em desuso em uma rede varejista do Brasil
(Universidade Federal do Pará, 2023-07-05) OLIVEIRA, Camila Martins; SENA, Luann Wendel Pereira de; http://lattes.cnpq.br/6233488431016391; https://orcid.org/0000-0001-9363-5766
Introduction: The reverse logistics process of disused or expired medicine for the general population makes the reverse flow, returning along its production and distribution chain, to have its final disposal environmentally sound. In this sense, the pharmacist is fundamental because he plays the role of knowledge multiplier, qualifying, training, and instructing employees and consumers about good environmental practices related to health waste. Objective: To carry out a situational diagnosis of reverse logistics and spatial analysis of expired or disused household medications in a pharmaceutical retail chain in Brazil. Method: It is an exploratory, cross sectional, and prospective study that used product/waste information obtained at different collection points in a network of pharmacies with 400 establishments in Brazil, from 2020 to 2022. Results: The study showed that the network collected a volume of 4,519.74 kg of expired medicines from the population between 2020 and 2022, concentrating the largest collection volume in the North region (69.1%). It is also noteworthy that Belem was the municipality with the highest collection, concentrating 92.5% of the collection in the state of Pará. Another important point was the presentation of a manual for the implementation of reverse logistics for expired medicines for the population. Conclusion: The findings of this study should contribute to the improvement and application of reverse logistics for expired medicines for the population in Brazil.
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Estudos químico-farmacêuticos, atividade antitumoral e mutagênica de Eleutherine plicata. Herb.
(Universidade Federal do Pará, 2020-11-03) CASTRO, Ana Laura Gadelha; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390; https://orcid.org/ 0000-0002-3328-5650; DOLABELA, Maria Fâni; http://lattes.cnpq.br/0458080121943649; https://orcid.org/ 0000-0003-0804-5804
Naphthoquinones have been linked to antitumor activity; however, they can cause DNA damage and be mutagenic. Some of these as the isoeleutherine and eleutherine, present in Eleutherine plicata Herb., do not have studies of mutagenicity and antitumor activity. This study evaluated the antitumor potential of the ethanolic extracts of E. plicata (EEEP), the fraction in which the quinones were found (Fraction dichloromethane-FDEP) and the genotoxic potential related to these substances. For understanding whether fractionation influences antitumor activity, EEEP was obtained by macerating the bulbs, it was fractionated under reflux and FDEP was obtained and fractionated in an open chromatographic column, resulting in the isolatation of eleutherine, isoeleutherine and eleutherol. Chemical-pharmaceutical studies were carried out: silica toxicity and pharmacokinetics (PreADMET), docking and dynamics. The antitumor activity was evaluated through the cytotoxicity in tumor cell line (oral cancer-SCC-9) and normal cell line (human keratinocytes-HaCaT), three-dimensional assay in spheroid model and cell migration in the same lines. Genotoxicity and mutagenicity were evaluated in Allium cepa model, the results of the isolated compounds were similar to those obtained in silico studies. In addition to the isoeleutherine and eleutherine, eleuterol was isolated from FDEP, the silica evaluation demonstrated similar pharmacokinetic profiles between these compounds. In the evaluation of anti-tumor activities, the EEEP fractionation contributed negatively to the activity, with EEEP (SCC09: IC50 = 12.87 ± 0.86 and HaCaT: 28.81 ± 1.82µg/mL) being the most promising with higher selectivity index for the tumor cell, interfering in the speed and directionality of tumor migration. Trying to understand this result, the capacity of naphthoquinones bind to Topoisomerase II (TOPII) was evaluated, confirming that they bind in its pouch, stabilizing the DNA-TOP II complex. In contrast, eleutherine proved to be more genotoxic, increasing the rate of mitosis, of aberrations, with micronucleus, bud and bridge being observed in the metaphase phase. However, it was not possible to differentiate the toxicity of eleutherine and isoleutherine in silico studies (Algae, Daphinia, fish and mutagenicity), obtaining similar results. In summary, EEEP is promising as a cytotoxic agent in tumor cells, and in the prevention of squamous cancer of the mouth. In relation to naphthoquinones, isoleutherine, due to its lower toxic potential and stabilization capacity of the DNA-TOP II complex, needs to be evaluated in other tumor strains.
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Síntese, caracterização e avaliação da atividade antimicrobiana e antiproliferativa de chalconas e derivados- in vitro
(Universidade Federal do Pará, 2020-12-21) ANJOS, Maricelia Lopes; BITENCOURT, Heriberto Rodrigues; http://lattes.cnpq.br/9418240134272692; https://orcid.org/ 0000-0002-0003-2876
In the present work we perform the synthesis, characterization and evaluation of antimicrobial and antiproliferative activities of chalcones and derivatives - in vitro. The interest in obtaining chalcones is due to the numerous pharmacological activities described in the literature for these classes of compounds that are intermediates for flavonoids. Thus, the synthesis and characterization of various chalcones and derivatives become important for the development of compounds with antimicrobial and antiproliferative activity. Ten substances were synthesized, containing seven chalcones and three naphthoflavanones, obtained by the Claisen Schmidt aldolic condensation reaction between acetophenones and aldehydes, at room temperature or with heating. Yields varied between 65.35% and 97.45%. Being characterized and confirmed by spectroscopic techniques. The antimicrobial activity in vitro was analyzed in the strains: Staphylococcus aureus; Enterococcus faecalis; Escherichia coli and Pseudomonas aeruginosa, following the microdilution protocol, however their inhibition result was not satisfactory. All substances were submitted to the cell viability test (MTT), to evaluate the antiproliferative activity in vitro, in gastric tumor line (AGP01), with comparison of dose response to the normal lung cell line (MRC-5). The substances AMB, 34M, MEB, PEB and EBA, showed significant cytotoxic activity. Which may represent new pharmacological possibilities, even because they have not been tested in this cell line.
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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/ 0000-0001-7495-9837
MMP-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.
Acesso aberto (Open Access)
Exposição ao MEHG provoca dano na medula espinhal: percepções a partir da análise proteômica e estresse oxidativo
(Universidade Federal do Pará, 2020-08-27) EIRÓ, Luciana Guimarães; LIMA, Rafael Rodrigues; http://lattes.cnpq.br/3512648574555468; https://orcid.org/ 0000-0003-1486-4013
Methylmercury (MeHg) is considered by the World Health Organization as one of the chemicals of greatest public health concern. Thus, knowing the susceptibility of central nervous system regions and the absence of evidence about the effects on the spinal cord, this study aimed to investigate proteomic and biochemical changes in the spinal cord after MeHg long-term exposure at low doses. For this, male Wistar rats were exposed to a dose of 0.04 mg/kg/day by for 60 days. After that, the proteome was identified with subsequent overrepresentation analysis (ORA). For the oxidative biochemistry, the antioxidant (ACAP, TEAC, GSH) and pro-oxidants (LPO and nitrite ions) parameters were evaluated. The proteomic analysis showed several altered proteins that participate in biological processes, cellular components, and molecular functions. There was an increase in total mercury (Hg) levels in the spinal cord, as well as an increase in LPO and nitrite ions and a reduction in ACAP, TEAC and GSH. Therefore, exposure to low doses of MeHg can trigger oxidative stress associated with changes in the proteomic profile.
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)
Obtenção, caracterização e microencapsulação de extratos ricos em antioxidantes naturais a partir do co-produto das amêndoas do tucumã (astrocaryum vulgare mart.)
(Universidade Federal do Pará, 2019-07-01) FERREIRA, Lindalva Maria de Meneses Costa; SILVA JÚNIOR, José Otávio Carréra; http://lattes.cnpq.br/4437885351749994; https://orcid.org/ 0000-0003-1691-1039
The purpose of this work was to microencapsulate the extract of the co-product of tucumã seeds (Astrocaryum vulgare Mart.) by spray drying using maltodextrin as a encapsulating agent. The techniques of thermogravimetry and Infrared analysis, water activity, scanning electron microscopy and electrophoretic mobility served to characterize the microencapsulated extract. The total of polyphenols, flavonoids and condensed tannins of the microencapsulated extract was determined by UV spectroscopy and identified by ultra high performance liquid chromatography, the antioxidant activity was measured by ABTS and DPPH. The microparticles showed heterogeneity, spherical structure and no cracks, confirming the efficiency of the microencapsulation process using maltodextrin as an encapsulating agent. The microencapsulated extract values of phenolic compounds content entre 130 mg ± 0,024 e 104,7 mg EAG/100g ± 0,024, Total flavonoids 27,17 ± 0,002 e 25,36 mg QE/100g ± 0,004) and condensate tannin 62,07 100g ± 0,137 e 47,95 mg CE/100g ± 0,087 and good antioxidant activity for the two methods tested. The ultra high performance liquid chromatography analysis identified the presence of gallic acid and caffeic acid. In general, the results showed good utility of the tucumã co-product in the form of microparticles rich in antioxidant compounds, which can be exploited for future application in the food area as a functional food.
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)
Exposição a rifampicina e adesão ao tratamento da tuberculose pulmonar
(Universidade Federal do Pará, 2020-08-28) ELIAS, Gisely France Abrantes; VIEIRA , José Luiz Fernandes; http://lattes.cnpq.br/2739079559531098; https://orcid.org/ 0000-0003-4842-8762; VASCONCELOS, Flávio de; http://lattes.cnpq.br/3695753129639448; https://orcid.org/ 0000-0001-9568-6268
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis, generally affecting the lungs and leading to death. The Ministry of Health recommends for the treatment of new cases of pulmonary tuberculosis the association of chemotherapy drugs administered in two phases: the intensive one, which lasts two months, and Rifampicin (600 mg), Isoniazid (300 mg), Pyrazinamide (1600 mg) and Ethambutol (1100 mg) (2RHZE) and maintenance, for four months, when Rifampicin (600 mg) and Isoniazid (300 mg) (4RH) are administered. The full dose of medication is indicated for patients over 50 kg. A determinant of therapeutic success is the exposure of the bacillus for a certain period of time to effective concentrations of chemotherapeutic agents, that is, above the minimum inhibitory concentration (MIC), which in this case of rifampicin ranges from 0.05 µg / ml to 0.5 µg / ml, in addition, studies have shown that maximum plasma drug concentrations above 8.0 µg / ml are associated with a high rate of therapeutic success. However, there is a high intra and interindividual variation in the plasma concentrations of rifampicin in the usual therapeutic doses, caused by factors related to the patient and the drug dispensed, which can interfere with exposure, as well as the administered doses and anthropometric measurements of the patients. The aim of the present study was to investigate the factors that influence plasma concentration when exposed to rifampicin in the treatment of pulmonary tuberculosis in a Basic Health Unit in Belém / Pa. A cross-sectional and observational study was carried out of 70 cases of subjects of both sexes, with clinical, radiological and laboratory diagnosis of tuberculosis by M. tuberculosis, distributed in the intensive and maintenance phases of treatment. Plasma concentrations of rifampicin were determined, as well as anthropometric measurements of weight, height, fat percentage and abdominal circumference of each individual and the application of the Morisky-Green Test to assess adherence. Thus, the sample included in the study was composed mainly of adult men with low education and income. Plasma concentrations of rifampicin were above the minimum inhibitory concentration of M. tuberculosis indicating adequate exposure to the drug, which can be measured by the high proportion of patients who had smear conversion at the end of the first month of treatment. Sex was not a predictor of variation in plasma rifampin concentrations. The treatment phase was considered to be a predictor of variation in plasma drug concentrations. The concentrations of rifampicin were not associated with the Body Mass Index, waist circumference and fat percentage both in patients in the intensive phase and in those in maintenance of treatment. Adherence to tuberculosis treatment was 88.1% and 82.14% in patients in the intensive and maintenance phases, respectively. Plasma concentrations of rifampicin were not associated with the Morisky-Green Test.
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 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)
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/ 0000-0002-3328-5650
Dapsone (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.
Acesso aberto (Open Access)
A exposição prolongada ao fluoreto durante a adolescência à fase adulta modula o proteoma hipocampal e gera danos cognitivos associados a um padrão neurodegenerativo no hipocampo de camundongos
(Universidade Federal do Pará, 2021-11-19) BITTENCOURT, Leonardo de Oliveira; GOMES, Bruna Puty Silva; http://lattes.cnpq.br/3013433540155834; https://orcid.org/ 0000-0001-5570-8530; LIMA, Rafael Rodrigues; http://lattes.cnpq.br/3512648574555468; https://orcid.org/ 0000-0003-1486-4013
Fluoride (F) is used in artificial water fluoridation due to its anticariogenic activity, but it is also present in soils and natural reservoirs due natural high levels or anthropogenic actions, featuring it as a potential environment toxicant. In addition to skeletal and dental fluorosis in people living in regions with high F levels, some studies have explored the association between F exposure and cognitive damages, and although the evidences have indicated that only high levels pose a deleterious effect on cognition, a heated debated has grown regarding the safety of water supply artificial fluoridation. In this way, this study investigated whether long-term F exposure, from adolescence to adulthood, under the paradigms of water fluoridation and environmental issue, would be associated with memory and learning impairments in mice, and unravel molecular and morphological aspects involved. For this, 21-days-old mice received for 60 days, 10mg/L or 50mg/L of F in drinking water; the control group received only water without addition of F. Then, the cognitive functions were assessed by the Morris Water Maze and Inhibitory Step-down Avoidance test, followed blood and hippocampus collection for plasma F level determination, and hippocampal global proteomic profile analysis by Mass Spectrometry. Some animals were perfused for immunohistochemical analyses of mature neurons density in CA1, CA3, hilus and dentate gyrus (DG) regions. The results indicated that prolonged exposure to F from adolescence to adulthood increased plasma F bioavailability, and the higher F concentration triggered short- and long-term memory impairments, being associated with the modulation of the global proteomic profile, and a neurodegenerative pattern in the CA3 and DG regions. Our data, in a translational perspective, gives evidences of potential molecular targets of F neurotoxicity in the hippocampus and reinforces the safety of low fluoride concentration exposure, besides the need for attention of people living in endemic regions.
Acesso aberto (Open Access)
Investigação da toxicidade oral aguda e propriedades farmacológicas de uma espécie do gênero Cassytha
(Universidade Federal do Pará, 2019-05-15) BARROS, Mayra Arouck; FONTES JÚNIOR, Enéas de Andrade; http://lattes.cnpq.br/7056265073849866; https://orcid.org/ 0000-0002-6186-9581
Plants have been present in human culture since its inception, being used for several purposes, including for the treatment of diseases. This practice has been handed down from generation to generation. The evolution of knowledge, however, demands broader approaches on plant species with therapeutic potential, in order to ensure safety and validate its traditional use. Cassytha filiformis, a species of the genus Cassytha, is used in folk medicine to treat cancer, trypanosomiasis, kidney disease and gonorrhea. Among its proven activities, the antiplatelet, vascular relaxing, antioxidant, cytotoxic, antihypertensive, hepatoprotective, antiepileptic, diuretic and alpha-adrenergic receptor antagonist effects stand out. Among its secondary metabolites, alkaloids have been identified for therapeutic benefit. To date, however, there are no studies that support the safety of its therapeutic application or that explore possible anti-inflammatory properties as the basis for its therapeutic actions. Acute oral toxicity was assessed according to OECD 425. Starting from an administration of 2000 mg / kg (v.o) of extract in rats, the hippocratic signs of toxicity, spontaneous locomotor activity, weight gain, water and food consumption, as well as relative body weight and hematological patterns at the end of the period. The antinociceptive activity was evaluated in mice, using the acetic acid induced writhing test and the formalin test (CEUA nº 1050140817). The cutoff dose of the extract did not promote hipocratic signs of toxicity or death. There were also no changes in feed and water consumption or weight gain patterns. The evaluation of the relative weight of organs (liver, kidneys, stomach and heart) and hemogram showed equivalent standards between treated and control animals. Cas01 also did not impair the locomotor activity of the animals. Cas01 was shown to have no influence on the contortions induced by acetic acid, nor did it promote significant alterations on formalin-induced biphasic nociception. These findings demonstrate for the first time that Cas 01 is a xenobiotic of low acute oral toxicity. They also demonstrate that their therapeutic actions do not involve nociceptive or inflammatory mechanisms.
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)
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)
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)
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 do efeito neuroprotetor da cafeína em ratas intoxicadas por etanol no padrão binge
(Universidade Federal do Pará, 2019-05-03) BARROS, Mayara Arouck; FERNANDES, Luanna de Melo Pereira; http://lattes.cnpq.br/0156144290849777; https://orcid.org/0000-0001-7004-0719; MAIA, Cristiane do Socorro Ferraz; http://lattes.cnpq.br/4835820645258101
Ethyl alcohol is a substance consumed since the dawn of mankind, extending to the present day. In this context, adolescents are attracting attention because consumption in this group is constantly rising, especially in the Binge Drinking pattern. This model of consumption leads to functional impairments, such as symptoms associated with anxiety and depression. For this reason, has been sought bioactive compound to prevent such damages, among them we can highlight the caffeine, substance widely consumed in the world. In view of this, this paper aims to investigate the neuroprotective effect of caffeine in self administration on the damages caused by EtOH intoxication in the binge pattern, aiming at an alternative to minimize the neurotoxic damages promoted by alcohol with the simple habit of drinking coffee. For this, Wistar rats, females, age 35 days (n = 40) were used. At treatment, animals received caffeine repeatedly from the 35th to the 72nd postnatal day (PND). Caffeine was administered as a 0.3g / L caffeinated solution in self-administration in the active period, starting 14 days before the first day of ethanol intoxication and persisting during the 4 weeks of BD. For ethanol intoxication in the binge pattern, it was administered by gavage at a dose of 3 g / kg / day (20 w / v) for three consecutive days weekly in the animals from the 49th to the 72nd PND. For behavioral tests, the animals were exposed to Open Field, Elevated-plus-maze, Splash and Forced swimming test. In relation to the anxious type behavior, the Caffeine + EtOH Group showed a significant increase in the distance and time traveled in the central area in the Open Field Test when compared to the EtOH group. In the LCE Test, the EtOH group showed reduction in %EBA and %TBA when compared to the control group. However, the caffeine group showed reversion when increasing both parameters when compared to the EtOH group. In the depressive-type behavior, the EtOH-intoxicated group presented reduction of the grooming time and increased immobility time, in the Splash and Forced Swim tests, respectively. The EtOH + Caffeine group was able to increase grooming time in the first test and reduce immobility time in the second. Thus, we can conclude that chronic consumption of caffeine promoted neuroprotection by reversing symptoms similar to anxiety and depression
Acesso aberto (Open Access)
Investigação fitoquímica e avaliação da atividade anti inflamatória do extrato hidroetílico de folhas de salix humboldtiana em modelo zebrafish (Danio rerio)
(Universidade Federal do Pará, 2021-09-25) RAMOS, Uêbem Fernandes; BARBOSA, Wagner Luiz Ramos; http://lattes.cnpq.br/1372405563294070; https://orcid.org/ 0000-0002-2421-8245
The leaves of Salix humboldtiana, family Salicaceae, are used in traditional medicine for the treatment of various inflammatory diseases, febrile states, among others. However, there is little information about the species in the literature. However, the genus Salix has a very significant diversity of uses in popular medicine, with Salix alba L. as its most renowned representative, which is included in the Brazilian Pharmacopoeia Form of Herbal Medicine. This work proposes to investigate chemical constituents with an emphasis on phenolic compounds, through pharmacognostic studies (analysis of physical-chemical quality); the phytochemical approach, the tests, served to demonstrate the presence of classes of secondary metabolites: reducing sugars, phenols and tannins, flavonoids, catechins, steroids and coumarin derivatives; fractionation, CCD and CLAE-DAD. In addition to biological testing on an animal model (D. rerio) to investigate anti-inflammatory activities. In this sense, the objectives of performing the phytochemical analyzes and the bioassay, the Salix humboldtiana Ethyl Extract (EBSh) was used in different doses in in vivo tests. Groups previously treated with 75 mg / kg EBSh showed 5% inhibition; 150 mg / kg showed 14% inhibition; 300 mg / kg showed 54% inhibition; 500 mg / kg showed 60% inhibition, 750 mg / kg showed 43% inhibition of abdominal edema compared to the negative control. Among the five different concentrations of EBSh tested and evaluated in the zebrafish model, the concentration of 500 mg, provided a statistically more expressive response regarding anti-inflammatory activity and anti-edematogenic degree after 5 h of treatment. This response was superior to the indomethacin standard when compared to the negative control, thus indicating the ability to reduce and / or inhibit edema in the peritoneal region. The animals subjected to the tests showed changes in normal behavior at all doses tested, these changes varied according to the concentration of EBSh administered. In the three lowest doses (75 mg, 150 mg and 300 mg), the fish showed only mild to moderate changes and less frequently, while in the two highest concentrations (500 mg and 750 mg), they manifested important behavioral changes, some with greater frequency and intensity.