Ciências Farmacêuticas

URI Permanente desta comunidade

http://repositorio.ufes.br/handle/10/17568

Programa de Pós-Graduação em Ciências Farmacêuticas

Centro: CCS
Telefone: (27) 3335-7360
URL do programa: http://www.farmacia.vitoria.ufes.br/pt-br/pos-graduacao/PPGCFAR

Navegar

Agora exibindo 1 - 12 de 12

Avaliação do potencial antifúngico e da citotoxicidade de derivados semissintéticos do eugenol
(Universidade Federal do Espírito Santo, 2019-06-24) Dutra, Jessyca Aparecida Paes; Kitagawa, Rodrigo Rezende; Schuenck, Ricardo Pinto; Fronza, Marcio; Jamal, Claudia Masrouah
The increase of resistant fungal infections directed the search for alternative strategies in order to identify new therapeutic approaches. Among these strategies is the molecular modification, which aims to obtain derivatives from synthetic or natural compounds. In the essential oil of clove is present eugenol, a phenolic with ample antifungal activity and structural patterns that favor the obtaining of analogues. In this context, the present study evaluated the antifungal and cytotoxic activity of eugenol analogues. The antifungal action was evaluated in vitro on Candida albicans and C. parapsilosis through minimal inhibitory (MIC) and minimal fungicide (CFM) concentration, and in silico on CYP51 by molecular docking. The evaluation of the morphological damage to the yeasts was performed through SEM. Basal and post-metabolic cytotoxicity were evaluated in vitro on cell lines by the MTT-tetrazolium test. In this study the derivatives 2 and 4, allyl chain present, presented greater antifungal action. However, derivatives 5 and 6 that undergo changes in the side chain showed activity similar to or less than eugenol. The evaluation of modes of interaction at the CYP51 site demonstrated that derivatives 2 and 4 have structural patterns essential for the interaction when compared to fluconazole. Both derivatives showed similar morphological changes to fluconazole, reinforcing the hypothesis of interaction with the active site of CYP51. These derivatives had baseline IC50 values of 34.57 and 14.60 μg/mL, respectively. Whereas 2 was less cytotoxic than amphotericin B, and more cytotoxic than fluconazole from 50μg/mL. Derivative 4 was more cytotoxic than both standards from 25μg/mL. However, after exposure to the S9 system, derivative 4 maintained cytotoxicity while 2 was more cytotoxic. Regarding the selectivity, derivative 2 showed higher SI for fungal cells when compared to 4 and eugenol. It was found that none of the analogs attended all desirable aspects. Some were more active while others presented reasonable cytotoxicity and varied profiles of selectivity and liver metabolism. In this way, it is concluded that derivatives 2 and 4 are attractive as prototypes for future antifungal drugs. However, directed changes should be based on the results obtained, in order to contribute to the expansion of the limited therapeutic arsenal with more active and less cytotoxic drugs
Caracterização de implantes poliméricos biodegradáveis contendo sirolimus e avaliação de sua estabilidade em condições de estresse químico
(Universidade Federal do Espírito Santo, 2016-03-18) Campos, Michele Soares Tacchi; Oliveira, Marcelo Antônio de; Jamal, Claudia Masrouah; Nogueira, Fernando Henrique Andrade
The use of sirolimus and its analogs has been evaluated in studies aimed at combating several types of cancer; however, because of the limited bioavailability of the drug, the search for new forms of administration is required. Biodegradable polymeric implants containing sirolimus were assessed as an alternative method of drug administration. Distinct implants containing 25% (w/w) sirolimus were prepared employing the polymer matrices chitosan, polycaprolactone and Poly(lactic-co-glycolic acid) (PLGA) in two proportions: PLGA 50:50 and PLGA 75:25. Thermal analysis techniques such as thermogravimetry and differential scanning calorimetry, combined with x-ray diffraction and microscopy were used to characterize and evaluate the compatibility of the constituents of the formulation, no incompatibilities were found between the components, but drug amorphization was observed in all samples. Sirolimus was unstable when exposed to conditions: heat, neutral and basic hydrolysis, at the analysis by high-performance liquid chromatography (HPLC ) were detected two degradation products after exposure to heat and detected one degradation product after basic hydrolysis and neutral hydrolysis, the degradations product showed similar UV spectrum to the drug’s spectrum. Through the isothermal kinetic study on solid media, it was observed that the drug molecule degrades second diffusive three-dimensional model, with validity time to 6 years. HPLC analysis showed that the lyophilized powder for elaboration of the implant prepared with PLGA 75:25 did not present degradation products and maintained its appropriate drug content of 24,6%, after analysis in solution by HPLC, and represents the most suitable polymer for use in developed by biodegradable implants containing Sirolimus for the treatment of malignant solid tumors, however, is still necessary to further study the drug effects after amorphization of the crystal and also stability and solubility analysis
Derivados triazólicos de isatina como potenciais agentes herbicidas
(Universidade Federal do Espírito Santo, 2019-03-11) Britto, Karolinni Bianchi; Morais, Pedro Alves Bezerra; Borges, Warley de Souza; Lacerda Junior, Valdemar; Costa, Adilson Vidal
Isatin (1H-indole-2,3-dione) is an important indole-type heterocycle found in plants, animals, fungi and also in humans. Studies have shown that isatin, as well as its derivatives, have a broad spectrum of activity, including herbicidal activity. The triazole ring is also of great relevance for medicinal chemistry because it acts not only as a pharmacophoric group but also acts as a bridge between biomolecules of interest for the formation of hybrids and also works to improve the pharmacological and pharmacokinetic properties of the drugs. Considering the importance of isatin and triazoles, known in the literature for various activities, the work was directed to the synthesis of isatin hybrids by the preparation of new isatin-N-1 substituted triazole derivatives via the click chemistry strategy by azido cycloaddition (CuAAC), preparation of isatin derivatives by N-alkylation, as well as in vivo evaluation, by germination test and initial development against lettuce (Lactuca sativa) and onion (Allium cepa). NMR 1H and 13C, HSQC, HMBC, COSY, IR and HRESIMS analyzes confirmed the achievement of all compounds. For the herbicidal assay, the synthesized compounds were diluted in 0.1% DMSO solutions at the concentration of 100 mg.L-1 and tested for both seeds. The evaluated variables were percentage of germination, germination speed index, shoot length, root length and fresh mass. Eighteen compounds were synthesized, of which thirteen are unpublished in the literature. As regards the activity of isatin derivatives, it is noted that there is an effect on the initial development and growth of the seedlings, demonstrated by the inhibition of lettuce shoot length and onion root length evaluated mainly by compounds 65 and 71, respectively. Thus, some evaluated compounds exhibited properties suggesting their potential utility as herbicides; however, further and further tests are necessary for this action to be proven, as well as for the structural optimization of these derivatives towards the discovery of new, more potent inhibitors, in view of the emergence of weeds resistant to currently available inhibitors
Efeito tipo-anticompulsivo agudo da Ketamina : envolvimento do córtex orbitofrontal e dos receptores AMPA
(Universidade Federal do Espírito Santo, 2018-08-24) Tosta, Cristina Luz; Harres, Vanessa Beijamini; Moreira, Fabrício de Araújo; Bortoli, Valquíria Camin de
Previous clinical and pre-clinical studies suggest the involvement of orbitofrontal cortex (OFC) and glutamatergic neurotransmission in obsessive-compulsive disorder (OCD). Ketamine, a non-competitive NMDA glutamatergic receptor antagonist, has shown a rapid and long lasting antidepressant effect. The antidepressant effect of ketamine seems to be mediated not only by directly blockade of NMDA receptors, but also by activation of AMPA glutamatergic receptors, increase in extracellular serotonin (5-HT) levels linked to activation of 5-HT1A receptors, and reduction of nitric oxide (NO) synthesis associated to inhibition of nitric oxide synthase (NOS). Ketamine also seems to have rapid anti-obsessive and anti-compulsive effects in clinical and pre-clinical studies. However, there are not studies published so far investigating the mechanisms responsible for this effect of ketamine. Thus, we assessed whether the anticompulsive-like effect of S-ketamine in mice exposed to the marble-burying test (MBT) involves the OFC and depends on activation of AMPA receptors, facilitation of serotonergic neurotransmission and inhibition of nitrergic pathway. Results showed that systemic (10 mg/kg) and intra-OFC (10 nmol/0.1 μl/side) administration of Sketamine reduces marble burying behavior without affecting spontaneous locomotor activity, suggesting an acute anti-compulsive-like effect. In addition, pre-treatment with NBQX (3 mg/kg; AMPA receptor antagonist) blocked the anti-compulsive-like effect of S-ketamine. However, pre-treatment with p-CPA (150 mg/kg/day; 5-HT synthesis inhibitor), WAY100635 (3 mg/kg; 5-HT1A receptor antagonist), or L-arginine (500 mg/kg; nitric oxide precursor) did not counteract S-ketamine effect in the MBT. Moreover, associating sub-effective doses of L-NAME (10 mg/kg; NOS inhibitor) and S-ketamine (3 mg/kg), which did not induce any per se effect, promoted an anticompulsive-like effect. In conclusion, the anti-compulsive-like effect of S-ketamine appears to be a result of its action on OFC, depends on activation of AMPA receptors and also seems to involve the nitrergic pathway
Efeitos de anestésicos gerais utilizados em cirurgias experimentais em ratos submetidos a testes preditivos de efeito ansiolítico e antidepressivo
(Universidade Federal do Espírito Santo, 2017-03-27) Paula, Letícia Santos Herbst de; Sampaio, Karla Nívea; Harres, Vanessa Beijamini; Natalini, Cláudio Corrêa; Joca, Samia Regiane Lourenço
In experimental psychopharmacology, the behavioral evaluation is often preceded by stereotactic surgery to insert cannulas or electrodes in the central nervous system. During these surgeries, the rodents receive anesthetic and analgesic drugs to prevent unnecessary suffering. Previous studies showed that some general anesthetics, such as ketamine, induce acute and persistent antidepressant and anxiolytic-like effects. In this way, we evaluated whether other general anesthetics would also affect behaviors that would compromise the experimental data interpretation of other studies. Thus, we evaluate if tribromoethanol, chloral hydrate, thiopental and isoflurano would change behavior of animals submitted to the Forced Swimming Test (FST) and to the Elevated Plus-Maze (EPM). In a second experiment, we evaluate if an anesthetic dose of anesthetics that did not affect the analyzed behavior in the first experiment, could interfere with the detection of the antidepressant (imipramine) or anxiolytic (diazepam) effects in rats subjected to the TNF or LCE, respectively. Adult Wistar rats were intraperitoneally injected (single injection) with subanesthetic and anesthetic doses of chloral hydrate (50, 150 and 400 mg/kg); tribromoethanol (40, 90, and 250 mg/kg) or thiopental (05, 15 and 40 mg/kg). The control group received saline injections. Isoflurane was administered by inhalation in anesthetic dose (4% to induction and 2% for maintenance) or in subanesthetic doses (0,5, 1,5%), and the control group received air. The animals were tested in the FST 2 h and 7 days after injections. Independent groups of animals were tested in the EPM and in the open field (OF) 2 hours or 7 days after injection of the anesthetics. Tribromoethanol did not acutely (2h) or persistently (7 days) affect behaviors in the FST. Tribromoethanol (90mg/kg) increased exploration of the open arms in the EPM, indicating an acute anxiolytic-like effect. The anesthetic dose of tribromoethanol (250mg/kg) decreased the open arms exploration in the EPM 7 days after treatment, suggesting a delayed anxiogenic-like effect. A subanesthetic dose of chloral hydrate (150 mg/kg) reduced immobility time in the FST only acutely, suggesting an antidepressant-like effect. The anesthetic dose of chloral hydrate (400mg/kg) raised the exploration of the open arms in the EPM 2 h and 7 days after treatment, suggesting an acute and persistent anxiolytic-like effect. The anesthetic dose of thiopental (40mg/kg) acutely reduced immobility time and frequency in the FST, suggesting an antidepressant-like effect. Thiopental did not affect behaviors in the EPM. Isoflurano did not present any effect on behavior of TNF or EPM. The general anesthetics did not interfere in the detection of the antidepressant or anxiolytic effect of imipramine or diazepam, respectively. Our results showed that tribromoethanol and chloral hydrate are improper anesthetics in surgeries that precede behavioral tests related to anxiety, while isoflurane and thiopental proved to be suitable for use in this tests. The subanesthetic doses of tribromoethanol (90mg/kg) and chloral hydrate (150mg/kg) induce acute anxiolytic and antidepressant-like effects, respectively, while an anesthetic dose of thiopental induced acute antidepressant effect, suggesting that these drugs may be target of future studies for developing potential new medicine to treat anxiety and depression disorders.
Estudo de solubilidade e das atividades antioxidante e anti-Helicobacter pylori da isocumarina paepalantina obtida de Paepalanthus latipes Silv.
(Universidade Federal do Espírito Santo, 2016-03-24) Damasceno, João Paulo Loureiro; Giuberti, Cristiane dos Santos; Kitagawa, Rodrigo Rezende; Schuenck, Ricardo Pinto; Khalil, Najeh Maissar
Helicobacter pylori is a Gram-negative bacteria that infects the gastric mucosa, causing disorders like gastritis, peptic ulcers and stomach cancer, and which eradication is difficult. The standard treatment is not always successful because of its side effects, high costs and poor patient compliance, leading to the search for new drugs. In this context, the isocoumarin paepalantine, 9,10-dihydroxy-5,7-dimethoxy1H-naphtho (2,3c) pyran-1-one, isolated from the capitula of Paepalanthus bromelioides, has demonstrated a broad range of biological activities such as antibacterial, antioxidant, anti-inflammatory and cytotoxic. Among these, the antimicrobial and antioxidant activities stand out and allow the evaluation of the effects of H. pylori infection and the modulation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) involved in this process. The molecule is poorly studied and there are few data in the literature on its solubility, including a viable alternative to the use of DMSO as a solvent, considering its toxicity in cell culture and interference in the antioxidant activity tests. Thus, the goal of this study was to evaluate alternative solvents to DMSO and validate an analytical spectrophotometric method using a suitable solvent for the antioxidant assays of radical scavenging activity (DPPH and ABTS), ROS (HOCl, OH● , O2 -● , H2O2), RNS (NO● ), and anti-H. pylori activity. Among the evaluated solvents, propylene glycol at pH 7.5 was the solvent of choice. The results suggest less interference in the assays compared to DMSO and that it is a viable alternative from a technological point of view. The results show a strong antioxidant activity of paepalantine in comparison to Trolox®. In addition, it was observed a significant effect on H. pylori culture with MIC of 128 μg/ml, MBC of 256 μg/ml, and a synergism of its sub-MIC doses with amoxicillin and metronidazole. This demonstrates a possible action on the permeability of bacterial membrane by inhibition of Penicillin-Bindind Proteins (PBPs), as observed through morphological changes using scanning electron microscopy. Therefore, paepalantine is promising for the development of drugs to combat H. pylori and its associated disorders.
Estudo de utilização de medicamentos em pacientes com doença de Parkinson
(Universidade Federal do Espírito Santo, 2019-02-22) Colatto, Luana Laura; Ayres, Lorena Rocha; Guimarães do Bem, Daniela Amorim Melgaço; Baldoni, André de Oliveira; Andrade, Tadeu Uggere de
Aging is leading to an increasing incidence of chronic degenerative illnesses such as Parkinson’s disease. In addition, the elderly population is characterized by the concomitant presence of one or more chronic conditions that bring with it the challenge of polypharmacy, and with it the complexity of therapeutic regimens. Potentially inappropriate medications, which can cause severe adverse effects when given to the elderly, may interfere with the success of pharmacotherapy in these patients. Together with all these factors, depression and sociodemographic characteristics may influence adherence to pharmacological treatment. In this context, we identified the prevalence in the use of potentially inappropriate medications, according to the Beers criteria 2015 and, also, we evaluated the adherence to the drug treatment, both in patients with Parkinson’s disease. It is a cross-sectional study, developed in patients diagnosed with Parkinson’s disease and who are part of the Chronic Management Program of Unimed-Vitória. We evaluated the older adults with 60 years or more included in the digital Healthmap® platform in the year 2017. Data were collected using questionnaires (structured interview questionnaire, Hoehn and Yahr Scale, Morisky-Green Test, Brief Medication Questionnaire, MedTake) and through the digital Healthmap® platform. The association between the use of potentially inappropriate medications and the independent variables was analyzed by univariate logistic regression with their respective confidence intervals of 95%. For the multiple model, the variables that presented p < 0.20 were selected. The association between adherence and the independent variables was analyzed using Fisher's exact test. The prevalence of 83.3% was verified in the use of potentially inappropriate medications. In the multiple logistic regression model, the associated variables to use were female (p = 0.03), receive seven or more home visits (p = 0.03), some anatomical therapeutic chemical classification – code M: musculo-skeletal system (p = 0.04) and code A: alimentary tract and metabolism (p = 0.005), and the use of psychotropic medication (p = 0.03). Consulting with four or more different medical specialties was considered as a protection factor for the use of potentially inappropriate medications. The results found in the assessment of adherence ranged from 0.0% to 76.1%, considering total adherence to the prescribed treatment, according to the score of each questionnaire. There were no significant associations between the variables and adherence to treatment. This study demonstrated a high prevalence of potentially inappropriate medications in this population, evidencing the need to disseminate this criteria and the adoption of tools that promote the rational use of drugs and, on the other hand, a low therapeutic adherence of the patients, which corroborates the need for a multidisciplinary approach, particularly with the participation of a pharmacist, to develop strategies to facilitate understanding of the pharmacological treatment of patients with Parkinson’s disease.
Estudo do efeito de naftopiranonas de espécies de paepalanthus sp sobre Helicobacter pylori, macrófagos ativados e linhagem celular de adenocarcinoma gástrico
(Universidade Federal do Espírito Santo, 2018-03-19) Ardisson, Juliana Santa; Rodrigues, Ricardo Pereira; Kitagawa, Rodrigo Rezende; Fronza, Marcio; Schuenck, Ricardo Pinto
The naphthopyranones paepalantine and 5-methoxy-3,4-dehydroxanthomegnin were isolated from Paepalanthus sp and showed antioxidant, anti-inflammatory, antitumor and antimicrobial potential, including anti-H. pylori. H. pylori infection is one of the main causes of gastric cancer. The infection causes an excessive inflammatory response through the neutrophils and macrophages infiltration, increasing the release of reactive species and inducing the production of pro-inflammatory mediators. In the gastric environment, H. pylori expresses the urease enzyme, increasing the pH of the medium through ammonia production. In this context, our aim was to evaluate the activity of naphthopyranones in H. pylori, immunomodulation in macrophages and cytotoxic action in gastric adenocarcinoma cell line and to confirm the potential of interaction of these substances in the urease and iNOS binding sites through molecular docking studies. The determination of the minimum inhibitory concentration (MIC) of the naphthopyranones for H. pylori was performed by broth microdilution technique for further analysis of the synergistic activity with metronidazole and for morphological analysis by scanning electron microscopy (SEM). The evaluation of the urease inhibition by the naphthopyranones was performed in vitro and in silico. The immunomodulatory activity of naphthopyranones was evaluated detecting the nitric oxide and cytokines (TNF-α, IL-1β, and IL-6) released by macrophages, and the interaction potential of the naphthopyranones within iNOS binding site was studied in silico. The reduction of the pathogenicity of H. pylori in macrophages was investigated after treatment with sub-inhibitory concentrations of the naphthopyranones. Finally, cytotoxic activity in gastric adenocarcinoma cells (AGS) was evaluated by the MTT assay. 5-methoxy-3,4-dehydroxanthomegnin is shown to inhibit H. pylori (metronidazole resistant strain) synergistically with metronidazole, reducing its MIC to 8 μg/mL. The results of the scanning electron microscopy, that evaluated the H. pylori morphology, evidenced that the naphthopyrananones alter the H. pylori morphology, indicating a possible role on the Penicilin-binding protein (PBPs) due to the bacterial cell wall modifications. It was also verified that H. pylori grow under naphthopyranones sub-inhibitory concentrations causes reduction of the activation of macrophages by inhibition of NO production in 60.21 ± 1.8% for paepalantine and 47.50 ± 0.6% for 5- methoxy-3,4-dehydroxanthomegnin. Regarding urease inhibition, no significant inhibitory activity of the samples and no favorable interactions with the major aminoacid residues in the active site of this enzyme was observed. The samples demonstrated immunomodulatory potential by inhibiting the proinflammatory cytokines produced by LPS stimulated macrophages (TNF-ɑ inhibition of 36.07 ± 2.63% and 60.19 ± 0.12% and IL-6 inhibition of 36.91 ± 0.57% and 92.35 ± 0.15% of paepalantine and 5-methoxy-3,4-dehydroxanthomegnin respectively, both at 25 μg/mL) and NO (99.5 ± 5.31% for paepalantine and 76.9 ± 4.11% for 5-methoxy-3,4- dehydroxanthomegnin at a concentration of 12.5 μg/mL) and also demonstrated interaction potential in the active site of the iNOS enzyme. In addition, naphthopyranones demonstrated satisfactory cytotoxic activity in AGS, with IC50 of 24.56 ± 2.3 μg/mL for paepalantine and 17.45 ± 1.6 μg/mL for 5-methoxy-3,4- dehydroxanthomegnin. In general, the naphthopyranones demonstrate potential for future use in the treatment and prevention of H. pylori infection as well as the diseases related to this infection, especially gastric cancer.
Impacto das moléculas imunorregulatórias HLA-G e Galectina-1 e o fator de transcrição FOXP3 na evolução clínica de pessoas vivendo com HIV
(Universidade Federal do Espírito Santo, 2018-10-09) Cortelette, Natalia Alves; Palomino, Gustavo Martelli; Pancoto, João Alexandre Trés; Guimarães do Bem, Daniela Amorim Melgaço; Baruffi, Marcelo Dias
Acquired Immunodeficiency Syndrome (AIDS) is a disease caused by a chronic infection of the Human Immunodeficiency Virus (HIV). Since the beginning of the AIDS epidemic, there are more than 35 million deaths. HIV infection triggers inflammatory changes compared to those of the inflammation triggered by aging increasing the risk for age-related diseases and mortality. The association of chronic inflammation, immunosenescence and adverse effects of antiretroviral therapy (ART) provides the development of non-infectious comorbidities, typical of the elderly, in HIV patients, relatively younger, such as neurocognitive, cardiovascular, metabolic disorders, associated with the bone system and non-HIV cancers. Human leukocyte antigen (HLA)-G and Galectin-1 (Gal-1) are immunoregulatory molecules that favor the progression of HIV infection. The genetic polymorphism in the 3' UTR Insertion (Ins)/Deletion (Del) 3' untranslated region within exon 8 between the + 2961 to + 2974 sites of the HLA-G gene (rs371194629), genotypic frequencies (Del/Del) and (Ins/Del) have been associated with genotype and higher frequency (Ins/Ins) with the lowest production of this molecule. The transcription factor forkheadbox P3 (FOXP3) is related to the regulatory activity of CD4+CD25+ Tregs cells, and polymorphisms of this factor contribute to diminish or alter the functionality of these important cells in the course of HIV infection. In this study, the correlations between the 14 bp Ins/Del polymorphism of the HLA-G gene, the single nucleotide polymorphism (SNP) at the -2383 C/T position of the promoter region of the FOXP3 gene (rs3761549) and the expression of soluble forms of HLA-G (sHLA-G) and Gal1 with the comorbidities and viral load of HIV patients. Participants were genotyped using polymerase chain reaction (PCR) for HLA-G 14bp Ins/Del polymorphism and PCR with restriction fragment analysis (PCR-RFLP) for FOXP3 SNP -2338 C/T. Clinical data and viral load of the patients were collected in medical records. HLA-G and soluble Gal-1 were quantified by ELISA. HIV patients without comorbidities had a higher frequency of the Del/Del genotype of 14bp (p <0.0136; OR = 0.4431; 95% CI: 0.2333 - 0.8415) than patients with comorbidities. The allelic and genotype frequencies of FOXP3 SNP -2383 C/T were not statistically significant between patients and controls and patients with and without comorbidities. As expected, Ins/Ins patients with and without comorbidities expressed less sHLA-G than controls (p<0.0160). However, Ins/Ins patients with comorbidities expressed more Gal-1 than controls and Ins/Ins patients without comorbidities (p<0.0019). Interestingly, patients under ART, with high levels of Gal-1, with comorbidities and low sHLA-G levels, 9 had a significant positive correlation with viral load levels (r=0.9996; p=0,0173). Considering the results found in the present study, it is observed that high expression of sHLA-G and Gal1 can be associated with better or worse clinical outcome in HIV patients, respectively.
Impacto do acompanhamento farmacoterapêutico na adesão ao tratamento e no controle metabólico e inflamatório de pacientes com Diabetes Mellitus tipo II
(Universidade Federal do Espírito Santo, 2018-08-22) Santos, Mayara Paes; Gonçalves, Rita de Cássia Ribeiro; Guimarães do Bem, Daniela Amorim Melgaço; Baldoni, André de Oliveira; Ayres, Lorena Rocha
The aim of this study was to evaluate the impact of pharmacotherapeutic follow-up on adherence to treatment and on metabolic and inflammatory parameters in patients with T2DM. This was a prospective interventional study, in which 60 patients diagnosed with T2DM were selected from Family Health Units in the Maruípe territory of the city Vitória-ES. Patients received pharmacotherapeutic follow-up with individual guidelines every 2 months for a period of 6 months. For the pharmacotherapeutic follow-up, an adaptation of the SOAP methodology (Subjective, Objective, Evaluation and Plan) was used, and the Morisky-Green (TMG) and MedTake (MTT) tests were used to evaluate adherence and knowledge of the treatment. Clinical and anthropometric parameters were measured during pharmacotherapeutic follow-up. Biochemical parameters were investigated through tests of fasting glycemia, glycated hemoglobin, lipid profile, creatinine, gamma-GT, urea and uric acid. The inflammation evaluation was performed through the inflammatory markers: fibrinogen, C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). In addition, polymorphisms were investigated in the promoter regions of the fibrinogen (-148 C/T), IL-6 (-174 G / C) and TNF-α (-308 G/A and -238 G/A) genes. In this study, a significant increase (p <0.0001) in adherence and knowledge to the treatment after pharmacotherapeutic follow-up was found. Regarding the pharmacological treatment, patients improved (p <0.05) MTT for metformin, insulin and gliclazide, in TMG questions and in adherence to the types of treatments for T2DM, evidencing an improvement in adherence and knowlegde to the treatment. In addition, no significant changes in metabolic control, systolic and diastolic blood pressure, body mass index, weight, waist circumference, and capillary glycemia were observed. However, there was a significant increase for HDL-c levels and waistto-hip ratio (WHR). Regarding inflammatory markers, only fibrinogen significantly reduced (p = 0.0224). CRP, IL-6 and TNF-α did not suffer significant changes (p> 0.05). Polymorphism genes (SNPs) were not shown to be influential in plasma levels of fibrinogen, IL-6 and TNF-α (p> 0.05). Therefore, pharmacotherapeutic follow-up was relevant because it contributed to the improvement of adherence to treatment, knowledge about medications and levels of HDL-c and fibrinogen in patients with T2DM.
Influência da suplementação com ácido ascórbico e zinco na morfologia testicular de ratos Wistar expostos ao arsenito de sódio
(Universidade Federal do Espírito Santo, 2016-03-30) Altoé, Luciana Schulthais; Pirovani, Juliana Castro Monteiro; Pancoto, João Alexandre Trés; Gomes, Marcos de Lucca Moreira
Several studies has shown that exposure to heavy metal arsenic, an environmental contaminant, may result in toxic effects, acute or chronic, causing different disorders, including potentially leading to damage to male fertility. Substances with potential protective action has been investigated. These include zinc and vitamin C, substances with known antioxidant action, are cofactors of cell division and playing an important role in reproduction. The aim of this study was to evaluate testicular function in rats exposed to arsenic in the form of sodium arsenite, and the possible protective role of co-administration of zinc or vitamin C by seminal, biometric and morphological (morphometry and stereology) analysis of the testis. Male Wistar rats (60 days old) were divided into six groups of six animals each: (1) control (distilled water), (2) sodium arsenite (5 mg/kg), (3) vitamin C (100 mg/kg) (4) zinc chloride (20 mg/kg), (5) sodium arsenite and vitamin C and (6) sodium arsenite and zinc chloride. The dosages were administered daily by gavage for 60 days. At the end of the treatment period, all animals were sacrificed and testis and accessory organs were removed and weighed. Testis fragments were processed for analysis by light microscopy and one centimeter of the deferens duct was removed for seminal analysis. There were no significant changes in the biometrics in any groups, but changes in the Leydig cells and in the seminiferous tubules were showed. Arsenic reduces the tubular diameter and the germinal epithelium height, resulting in a lower number of spermatids per testicle gram. Vitamin C and zinc were able to protect the Leydig cells and the proportion of normal spermatozoa of arsenic effects. It can be concluded that chronic exposure to sodium arsenite alter the spermatogenic process, reducing the total number of normal sperm, which can lead reduce fertility in male rats, and that coadministration of vitamin C or zinc although not able to neutralize the numerical damage can increase the proportion of normal spermatozoa.
Tolerância induzida por drogas : efeito da associação in vitro de antimicrobianos em Stenotrophomonas maltophilia
(Universidade Federal do Espírito Santo, 2019-02-22) Ferreira, Mariana Abou Mourad; Santos, Kênia Valéria dos; Silva, Rodrigo Cayô da; Tavares, Sarah Goncalves
Introduction: Bacterial tolerance is characterized by the ability of a microbial population to survive the high concentrations of a bactericidal drug without alteration in the Minimum Inhibitory Concentration. At the end of the antimicrobial treatment, the tolerant strains multiply again, which may cause recalcitrant infections and facilitate resistance. Many studies relate antimicrobial exposure to tolerance induction. Although observed in several species, tolerance has not yet been investigated for the opportunistic bacillus Stenotrophomonas maltophilia, commonly exposed in the clinical scenario to antibiotics that have no action on this pathogen. Thus, our objective was to investigate whether the prior use of certain non-targeted antimicrobials induces cross-tolerance in S. maltophilia. Materials and methods: Qualitative and quantitative screening tests were performed to evaluate possible tolerance-inducing antimicrobials. In these assays, we exposed the S. maltophilia ATCC® 13637™ to daptomycin (DAP), vancomycin (VAN) and gentamicin (GEN) and evaluated the occurrence of cross-tolerance to the following drugs targeting S. maltophilia: sulfamethoxazole/trimethoprim (SXT), ceftazidime (CAZ) and levofloxacin (LVX). After the screening, strains with tolerance-induced characteristics were tested for genetic similarity by ERIC-PCR. To exclude the contamination hypothesis and confirm the genus and species of the strains, the MALDI-TOF MS was performed. To evaluate tolerance, the following tests were carried out: determination of the Minimum Bactericidal Concentration (MBC) / Minimum Inhibitory Concentration (MIC) ratio for LVX; adapted disk-diffusion test for SXT, CAZ, LVX, ticarcillin-clavulanate (TCC), chloramphenicol (CLO), minocycline (MIN) and polymyxin B (PXB) and time-kill curve for LVX, CAZ and ciprofloxacin (CIP). Results: After induction of the parental strain ATCC® 13637™ to DAP and VAN, three potentially tolerant strains (D25, V15.6 and V3.9) were isolated, whose genetic similarity to parental was confirmed by ERIC-PCR (100% similarity). The induced strains maintained the same MIC value of LVX as the parental strain (0.125 μg/mL), with the MBC/MIC ratio ranging from 2.64 to 3.04 among the induced strains. In the adapted disc-diffusion test, strain D25 showed high tolerance for LVX, CAZ and TCC. In the stationary phase time-kill curves against 50 times the MIC of LVX, strain D25 presented a minimum duration for killing 99,99% of all population (MDK99.99) higher than the parental. The survival rate was also higher for the D25 strain in the presence of CAZ (50xMIC). In general, strain D25 had a higher survival rate in all time-kill curves, except for CIP. Conclusions: Previous exposure of S. maltophilia to daptomycin induces cross-tolerance to levofloxacin, ceftazidime and ticarcillinclavulanate. Thus, erroneous empirical therapy with daptomycin could lead to the failure of these antimicrobials to eradicate S. maltophilia, culminating in chronic infections or death by a subpopulation of tolerant microorganisms.

Navegar

Navegando Ciências Farmacêuticas por Assunto "615.1"

Resultados por página

Opções de Ordenação