Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 297
Filtrar
1.
Biomed Pharmacother ; 149: 112921, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-36068780

RESUMO

The growing use of phytotherapy in clinical practice arouses interest in studies using medicinal plants as active ingredients for new medicines. Ipomoea pes-caprae has a wide medicinal use in the treatment of inflammatory disorders, skin wounds, stings, and painful rheumatic processes. Assayed in this study are the physicochemical characterization of a gel developed with this extract and the evaluation of its anti-inflammatory and healing efficacy, in addition to its antiedematogenic action on Bothrops snake envenoming in mice. The qualitative and quantitative analyses of the hydroethanolic extract by mass spectrometry showed 18 phenolic compounds, highlighting a high content of chlorogenic acid (0.92 µg/g), neochlorogenic acid (6.07 µg/g), and isochlorogenic acid (0.80 µg/g) compounds. The formulation was stable in relation to the physical-chemical characteristics during the time of analysis and was considered safe for topical treatment in animals, causing no skin irritation. Although the results have shown an absence of activity in the model of ear edema induced by croton oil (acute inflammation), the herbal gel efficiently inhibited carrageenan paw edema and chronic ear edema induced by multiple applications of croton oil, which may indicate the possible performance under the kinin pathway such as bradykinin, histamine, and serotonin. Wound healing in the group treated with the I. pes-caprae gel was accelerated compared with the placebo group, also confirmed through histological data. Edema induced by Bothrops erythromelas snake venom was efficiently reduced in the treatment with I. pes-caprae gel associated with the antibothropic-crotalic serum, whereas the antivenom alone was not effective. This approach presents a promising formulation based on I. pes-caprae with potential therapeutic use for inflammatory disorders.


Assuntos
Bothrops , Convolvulaceae , Ipomoea , Mordeduras de Serpentes , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antivenenos/farmacologia , Óleo de Cróton/farmacologia , Edema/induzido quimicamente , Géis/farmacologia , Camundongos , Fenóis/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Folhas de Planta/química , Mordeduras de Serpentes/tratamento farmacológico , Venenos de Serpentes/farmacologia , Cicatrização
2.
Reprod Toxicol ; 113: 42-51, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35981663

RESUMO

This study was conducted to evaluate the protective effects of epigallocatechin-3-gallate (EGCG) against ovarian toxicity in cyclophosphamide-treated mice and to verify the possible involvement of phosphorylated Akt, FOXO3a and rpS6 in the EGCG actions. Mice received saline solution (i.p.; control) or a single dose of cyclophosphamide (200 mg/kg body weight, i.p.) or mice were pretreated with N-acetylcysteine (150 mg/kg body weight, i.p.; positive control) or with EGCG (5, 25 or 50 mg/kg body weight, i.p.) once daily for three days followed by injection with single dose of cyclophosphamide (200 mg/kg body weight, i.p.). Thereafter, the mice were euthanized, and the ovaries were harvested and destined to histological (follicular morphology and activation), immunohistochemistry (cleaved caspase-3 and TNF-α) and fluorescence (mitochondrial activity and GSH concentrations) analyses. Furthermore, we examined the participation of p-Akt, p-FOXO3a and p-rpS6 in the protective effects of EGCG in cyclophosphamide-induced ovarian damage by immunohistochemical staining. The results showed that pretreatment with N-acetylcysteine or EGCG at 25 and 50 mg/kg before cyclophosphamide administration preserved the normal follicular morphology, prevented primordial follicle loss, reduced atresia, inflammation, and mitochondrial damage, and increased GSH concentrations compared to the only cyclophosphamide treatment. Additionally, pretreatment with 25 mg/kg EGCG regulated phosphorylated Akt, FOXO3a and rpS6 after cyclophosphamide treatment. In conclusion, short-time pretreatment with 25 mg/kg EGCG can prevent follicle loss in cyclophosphamide-treated mice by reducing oxidative damage, inflammation, and apoptosis, and regulating of p-Akt, p-FOXO3a and p-rpS6.

3.
Curr Top Med Chem ; 2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-35986522

RESUMO

BACKGROUND: Passiflora L. is a genus belonging to the Passifloraceae family, with many species widely used in folk medicine and several pharmacological activities described in the scientific literature, being a major target for the development of new therapeutic products. Studies have identified several bioactive compounds in their composition as responsible for these activities, mainly C-glycoside flavonoids. OBJECTIVE: The aim of this study was carry out a review of patents related to the genus and its application in several pharmacological activities, important for the development of new drugs and formulations. METHOD: The search was carried out in 5 specialized databases, INPI, EPO, WIPO, Latipat and Derwent, using the term 'Passiflora' combined with 'A61K and A61P', subclasses of the section A, of the International Patent Classification (IPC), which are destined to medical, dental or hygienic purposes, and therapeutic activity of chemical compounds or medicinal preparation, respectively. RESULTS: 1,198 patents, citing the genus in the title or abstract, have been found, 508 being duplicates. After exclusion and inclusion criteria, 23 patents written in English, Portuguese and Spanish were selected, which demonstrated biological assays in vivo with species of Passiflora as the only active constituent or incorporated in formulations with other compounds. CONCLUSION: The findings of this search showed growing interest in research and industrial areas, in the pharmaceutical development with species of Passiflora, suggesting that the different bioactive compounds present in the genus can be considered as an important tool for the development of new effective and safe products with pharmacological potential.

4.
Mar Drugs ; 20(8)2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-36005527

RESUMO

For more than 40 years, marine microorganisms have raised great interest because of their major ecological function and their numerous applications for biotechnology and pharmacology. Particularly, Archaea represent a resource of great potential for the identification of new metabolites because of their adaptation to extreme environmental conditions and their original metabolic pathways, allowing the synthesis of unique biomolecules. Studies on archaeal carotenoids are still relatively scarce and only a few works have focused on their industrial scale production and their biotechnological and pharmacological properties, while the societal demand for these bioactive pigments is growing. This article aims to provide a comprehensive review of the current knowledge on carotenoid metabolism in Archaea and the potential applications of these pigments in biotechnology and medicine. After reviewing the ecology and classification of these microorganisms, as well as their unique cellular and biochemical characteristics, this paper highlights the most recent data concerning carotenoid metabolism in Archaea, the biological properties of these pigments, and biotechnological considerations for their production at industrial scale.


Assuntos
Archaea , Carotenoides , Archaea/metabolismo , Biotecnologia , Carotenoides/metabolismo , Pigmentação
5.
Rev Bras Epidemiol ; 25: e220017, 2022.
Artigo em Inglês, Português | MEDLINE | ID: mdl-35830065

RESUMO

OBJECTIVE: To describe the performance of Primary Health Care, according to conglomerates of São Paulo cities that present homogeneous indicators. METHODS: This is a descriptive study, based on secondary data extracted from official sources of the Unified Health System, for the year 2018. An analysis matrix was created, with the proposition of performance (access, effectiveness and adequacy) and context indicators (population, health determinants and financing) selected and organized in dimensions and sub-dimensions. Cluster Analysis was used to identify the groups of homogeneous municipalities. RESULTS: 645 municipalities were divided in 6 conglomerates. Clusters 2 and 3 were formed predominantly by small municipalities with greater access to health; cluster 3 has less social vulnerability and greater investment in health. Clusters 1, 4 and 5 were formed by the largest municipalities with less access to health; cluster 4 presents greater social vulnerability, less coverage of private health plans and a greater percentage of health resources; cluster 5 was characterized by greater Gross Domestic Product per capita and greater coverage of private health plans. Cluster 6, formed by the city of São Paulo, was a particular case. Cluster 2 drew attention, as it was shown to have increased coverage, but signaled lower efficacy and adequacy levels. Cluster 3 had the best performance among all clusters. CONCLUSION: These findings can support regional and municipal management, given the complexity of the territory of São Paulo, pointing to scenarios that demand broader public management initiatives.


Assuntos
Programas Governamentais , Atenção Primária à Saúde , Brasil , Cidades , Humanos
6.
Am J Trop Med Hyg ; 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35895427

RESUMO

Some patients with visceral leishmaniasis (VL), or kala-azar, suffer relapses and low quality of life despite adequate drug therapy, especially those co-infected with HIV. Occasionally, physicians indicate splenectomy, but the benefit of the procedure needs to be analyzed systematically. Therefore, a retrospective open cohort study was conducted in Teresina, Brazil. Inpatients from a reference hospital with relapsing VL who had a rescue splenectomy between 2012 and 2019 after the nationally recommended drug therapy failed were studied. The procedure's risks and benefits were assessed in a limited-resource setting. The primary outcomes were surgical complications, complete blood count, CD4+ cell count, hospitalizations, survival time, and medical complications preceding death. Thirteen adult patients received medical and surgical indications of splenectomy (12 men and one woman). Eleven had HIV infection. Two had early and two had late complications. Four died, all of whom were infected with HIV. An additional HIV-coinfected patient, apart from the cohort, died just before surgery. The death rate after surgery was 13.3 overall and 22.1 per 100 person-years among HIV-infected patients (31% overall and 36%, respectively). The impressive rise of complete blood counts and reduction of blood transfusions and hospitalizations were observed among all patients. Also, a meaningful increase in CD4+ cells in HIV-infected patients was noted. Splenectomy may benefit patients with relapsing VL. However, before performing splenectomy, available combined drug therapy should be tried for relapsing VL.

7.
Biomed Pharmacother ; 151: 113131, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35643067

RESUMO

This study aimed to analyze the effects of the quercetin (100 mg/kg), 1% glutamine and 1% α-tocopherol antioxidants in the myocardium of rats with streptozotocin-induced diabetes mellitus. Twenty male rats were subdivided into four groups (n = 5): N (normoglycemic); D (diabetic); NT (normoglycemic treated with antioxidants); and DT (diabetic treated with antioxidants) treated for 60 days. Clinical parameters, oxidative stress markers, inflammatory cytokines, myocardial collagen fibers and immunoexpression of superoxide dismutase 1 (SOD-1), glutathione peroxidase-1 (GPx-1), interleukin-1ß (IL-1-ß), transforming growth factor-beta (TGF-ß), and fibroblast growth factor-2 (FGF-2) were evaluated. Results showed reduced body weight, hyperphagia, polydipsia and hyperglycemic state in groups D and DT. The levels of glutathione (GSH) were higher in NT and DT compared to N (p < 0.01) and D (p < 0.001) groups, respectively. Greater GSH levels were found in DT when compared to N animals (p < 0.001). In DT, there was an increase in IL-10 in relation to N, D and NT (p < 0.05), while GPx-1 expression was similar to N and lower compared to D (p < 0.001). TGF-ß expression in DT was greater than N (p < 0.001) group, whereas FGF-2 in DT was higher than in the other groups (p < 0.001). A significant reduction in collagen fibers (type I) was found in DT compared to D (p < 0.05). The associated administration of quercetin, glutamine and α-tocopherol increased the levels of circulating interleukin-10 (IL-10) and GSH, and reduced the number of type I collagen fibers. Combined use of systemic quercetin, glutamine and alpha-tocopherol attenuates myocardial fibrosis in diabetic rats.


Assuntos
Diabetes Mellitus Experimental , Quercetina , Animais , Antioxidantes/metabolismo , Colágeno/metabolismo , Diabetes Mellitus Experimental/metabolismo , Fator 2 de Crescimento de Fibroblastos/metabolismo , Fibrose , Glutamina/metabolismo , Glutationa/metabolismo , Interleucina-10/metabolismo , Masculino , Estresse Oxidativo , Quercetina/farmacologia , Quercetina/uso terapêutico , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Fator de Crescimento Transformador beta/metabolismo , alfa-Tocoferol/farmacologia , alfa-Tocoferol/uso terapêutico
8.
Biopreserv Biobank ; 2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35696235

RESUMO

The most common limitation of anticancer chemotherapy is the injury to normal cells. Cyclophosphamide, which is one of the most widely used alkylating agents, can cause premature ovarian insufficiency and infertility since the ovarian follicles are extremely sensitive to their effects. Although little information is available about the pathogenic mechanism of cyclophosphamide-induced ovarian damage, its toxicity is attributed to oxidative stress, inflammation, and apoptosis. The use of compounds with antioxidant and cytoprotective properties to protect ovarian function from deleterious effects during chemotherapy would be a significant advantage. Thus, this article reviews the mechanism by which cyclophosphamide exerts its toxic effects on the different cellular components of the ovary, and describes 24 cytoprotective compounds used to ameliorate cyclophosphamide-induced ovarian injury and their possible mechanisms of action. Understanding these mechanisms is essential for the development of efficient and targeted pharmacological complementary therapies that could protect and prolong female fertility.

9.
Pharmaceutics ; 14(5)2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35631654

RESUMO

One of the main reasons for cancer's low clinical response to chemotherapeutics is the highly immunosuppressive tumor microenvironment (TME). Tumor-ass ociated M2 macrophages (M2-TAMs) orchestrate the immunosuppression, which favors tumor progression. Extracellular vesicles (EVs) have shown great potential for targeted therapies as, depending on their biological origin, they can present different therapeutic properties, such as enhanced accumulation in the target tissue or modulation of the immune system. In the current study, EVs were isolated from M1-macrophages (M1-EVs) pre-treated with hyaluronic acid (HA) and the ß-blocker carvedilol (CV). The resulting modulated-M1 EVs (MM1-EVs) were further loaded with doxorubicin (MM1-DOX) to assess their effect in a mouse model of metastatic tumor growth. The cell death and cell migration profile were evaluated in vitro in 4T1 cells. The polarization of the RAW 264.7 murine macrophage cell line was also analyzed to evaluate the effects on the TME. Tumors were investigated by qRT-PCR and immunohistochemistry. MM1-DOX reduced the primary tumor size and metastases. NF-κB was the major gene downregulated by MM1-DOX. Furthermore, MM1-DOX reduced the expression of M2-TAM (CD-163) in tumors, which resulted in increased apoptosis (FADD) as well as decreased expression of MMP-2 and TGF-ß. These results suggest a direct effect in tumors and an upregulation in the TME immunomodulation, which corroborate with our in vitro data that showed increased apoptosis, modulation of macrophage polarization, and reduced cell migration after treatment with M1-EVs combined with HA and CV. Our results indicate that the M1-EVs enhanced the antitumor effects of DOX, especially if combined with HA and CV in an animal model of metastatic cancer.

10.
Front Oncol ; 12: 851003, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35615157

RESUMO

Penile leiomyosarcoma isz an extremely uncommon entity that rarely occurs in the glans. Due to the limited number of cases described in literature, guidelines regarding non-surgical treatment, prognosis, and management remain equivocal. Among the mesenchymal tumors of the penis, leiomyosarcoma has the highest propensity for recurrence. It originates in the smooth muscle cells from two distinct locations: superficial and deep. The deep subtype is the most aggressive and has the highest potential for metastasis. Surgical treatment should be implemented early and must be locally aggressive. Herein, we present a rare case of a 54-year-old patient with deep localized leiomyosarcoma of the glans, albeit with superficial characteristics. A review of the main histopathological, clinical, immunohistochemical, and therapeutic aspects of this unusual entity is presented.

11.
Vet Sci ; 9(5)2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35622757

RESUMO

Blood loss in sheep can have different causes and may result in anemia. We aimed to evaluate the clinical, hematological, and biochemical alterations and the oxidative stress generated by acute blood loss. Eighteen healthy sheep underwent phlebotomy to remove 40% of the blood volume and were evaluated clinically and by laboratory tests for clinical, biochemical, and blood gas variables and to assess oxidative stress before induction (T0), 30 min (T30 min), and 6 (T6 h), 12 (T12 h), and 24 h (T24 h) after blood loss. The sheep showed tachycardia from T30 min until T24 h, reduction in the hematocrit, number of erythrocytes, and hemoglobin concentration, with lower values at T24 h and increase in the number of leukocytes from T12 h on. There was a reduction in blood pH and oxygen pressure at T30 min, increased lactate concentration and reduced blood bicarbonate at this time. There was an increase in urea concentration from T6 h until the end of the study, with no change in creatinine levels. The animals did not show changes in the concentration of malonaldehyde, and in the activity of the enzymes superoxide dismutase, glutathione peroxidase, and catalase, but there was a reduction in the concentration of reduced glutathione at T24 h. The acute loss of 40% of blood volume is capable of promoting relevant clinical, hematological, blood gas, and biochemical alterations, and contributed to the appearance of oxidative stress with reduced glutathione concentration, suggesting that this process generated free radicals in sufficient quantity to diminish the action of antioxidants.

12.
Int J Mol Sci ; 23(8)2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35457057

RESUMO

Tumor growth and progression are linked to an altered lipid metabolism in the tumor microenvironment (TME), including tumor cells and tumor-associated macrophages (TAMs). A growing number of lipid metabolism targeting drugs have shown efficacy in anti-tumor therapy. In addition, exogenously applied lipids and lipid analogues have demonstrated anti-tumor activities in several cancers, including breast cancer. In this study, we investigated the anti-tumor efficacies of the natural lipids palmitic acid (PA), sphingomyelin (SM), ceramide (Cer) and docosahexaenoic acid (DHA) on breast cancer cells. All tested lipids reduced the malignancy of breast cancer cells in vitro by impairing cell proliferation, migration and invasiveness. PA showed superior anti-tumor properties, as it additionally impaired cancer cell viability by inducing apoptosis, without affecting healthy cells. Co-culture experiments further demonstrated that Cer and PA reduced the immunosuppressive phenotype of M2 macrophages and the M2 macrophage-promoted the epithelial-mesenchymal transition (EMT) and migration of breast cancer cells. At the molecular level, this coincided with the up-regulation of E-cadherin. Our results highlight a powerful role for exogenously applied PA and Cer in reducing breast cancer tumorigenicity by simultaneously targeting cancer cells and M2 macrophages. Our findings support the notion that lipids represent alternative biocompatible therapeutic agents for breast cancer.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Carcinogênese/metabolismo , Linhagem Celular Tumoral , Ceramidas/metabolismo , Ceramidas/farmacologia , Transição Epitelial-Mesenquimal , Feminino , Humanos , Macrófagos/metabolismo , Ácido Palmítico/metabolismo , Microambiente Tumoral
13.
Chem Biol Drug Des ; 99(6): 868-883, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35313075

RESUMO

Triterpenes α,ß-amyrin are naturally occurring molecules that can serve as building blocks for synthesizing new chemical entities. This study synthesized acyl, carboxyesther, NSAID, and nitrogenous derivatives and evaluated their antimicrobial activity. A cyclodextrin complexation method was developed to improve the solubility of the derivatives. Of the 17 derivatives tested, five exhibited activity against Trypanosoma cruzi, T. brucei, Leishmania infantum, Candida albicans, Staphylococcus aureus, and Escherichia coli. The 9a/9b mixture showed weak activity against the parasites (IC50 24.45-40.32 µM). However, it showed no activity for the other microorganisms. Derivatives 14a/14b exhibited potent activity against T. cruzi (IC50 2.0 nM) in this tested concentration did not show activity to the other microorganisms and were not cytotoxic. Derivatives 15a/15b and 16a/16b demonstrated relevant activity against the parasites (IC50 2.24-5.44 µM), but were also cytotoxic. Derivatives 17a/17b showed low activity against the tested parasites (IC50 21.70-22.79 µM), but they were selective since they did not show activity against other microorganisms. In docking studies, in general, all derivatives showed complementarity with the CYP51 binding site of the trypanosomatid mainly by hydrophobic interactions; thus, it is not conclusive that the molecules act by inhibiting this enzyme. Our results showed that triterpenes derivatives with antitrypanosomal activity could be synthesized by an inexpensive and rapid method.


Assuntos
Doença de Chagas , Leishmania infantum , Triterpenos , Trypanosoma cruzi , Humanos , Chumbo , Estrutura Molecular , Relação Estrutura-Atividade , Triterpenos/química , Triterpenos/farmacologia
14.
Sci Total Environ ; 828: 154426, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35278548

RESUMO

The Amazon rainforest is a heterogeneous ecosystem and its soils exhibit geographically variable concentrations of trace elements. In this region, anthropic activities - e.g., agriculture and mining - are numerous and varied, and even natural areas are at risk of contamination by trace elements, either of geogenic or anthropogenic origin. A reliable dataset of benchmark values for selenium (Se), barium (Ba), and iodine (I) concentrations in soils is needed for use as a reference in research and public policies in the region. In this study, 9 selected sites in the Brazilian Amazon rainforest within areas represented by Oxisols and Ultisols were assessed for relevant soil physicochemical characteristics, along with the concentrations of total Se (SeTot), total Ba (BaTot), and sequentially-extracted soluble Se (SeSol) and adsorbed Se (SeAd) in 3 different soil layers (0-20, 20-40, and 40-60 cm). In addition, organically bound-Se (SeOrg) and total I (ITot) concentrations in the surface layer (0-20 cm) were measured. Soil Se concentrations (SeTot) were considered safe and are likely a result of contributions of sedimentary deposits from the Andes. Available Se (SeSol + SeAd) accounted for 4.5% of SeTot, on average, while SeOrg in the topsoil accounted for more than 50% of SeTot. Barium in the western Amazon (state of Acre) and central Amazon (Anori, state of Amazonas) exceeded national prevention levels (PVs). Furthermore, the average ITot in the studied topsoils (5.4 mg kg-1) surpassed the worldwide mean. Notwithstanding, the close relationship found between the total content of the elements (Se, Ba, and I) and soil texture (clay, silt, and sand) suggests their geogenic source. Finally, our data regarding SeTot, BaTot, and ITot can be used to derive regional quality reference values for Amazon soils and also for updating prevention (PV) and investigation (IV) values established for selected elements by the Brazilian legislation.


Assuntos
Iodo , Selênio , Poluentes do Solo , Oligoelementos , Bário , Brasil , Ecossistema , Monitoramento Ambiental , Iodetos , Floresta Úmida , Selênio/análise , Solo/química , Poluentes do Solo/análise
15.
Chem Biol Interact ; 355: 109849, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35150652

RESUMO

A phytochemical investigation of cytotoxic extract and fractions of Cnidoscolus quercifolius Pohl led to isolation of five terpenoids, including three lupane-type triterpenes (1-3) and two bis-nor-diterpenes (4-5). Compounds 4 (phyllacanthone) and 5 (favelanone) are commonly found in this species and have unique chemical structure. Although their cytotoxic activity against cancer cells has been previously reported, the anticancer potential of these molecules remains poorly explored. In this paper, the antimelanoma potential of phyllacanthone (PHY) was described for the first time. Cell viability assay showed a promising cytotoxic activity (IC50 = 40.9 µM) against chemoresistant human melanoma cells expressing the BRAF oncogenic mutation (A2058 cell line). After 72 h of treatment, PHY inhibited cell migration and induced apoptosis and cell cycle arrest (p < 0.05). Immunofluorescence assay showed that the pro-apoptotic effect of PHY is probably associated with tubulin depolymerization, resulting in cytoskeleton disruption of melanoma cells. Molecular docking investigation confirmed this hypothesis given that satisfactory interaction between PHY and tubulin was observed, particularly at the colchicine binding site. These results suggest PHY from C. quercifolius could be potential leader for the design of new antimelanoma drugs.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Diterpenos/química , Euphorbiaceae/química , Proteínas Proto-Oncogênicas B-raf/genética , Tubulina (Proteína)/metabolismo , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/metabolismo , Sítios de Ligação , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular , Colchicina/química , Colchicina/metabolismo , Diterpenos/metabolismo , Diterpenos/farmacologia , Euphorbiaceae/metabolismo , Humanos , Melanoma/metabolismo , Melanoma/patologia , Simulação de Acoplamento Molecular , Mutação , Casca de Planta/química , Casca de Planta/metabolismo , Extratos Vegetais/química , Proteínas Proto-Oncogênicas B-raf/metabolismo , Tubulina (Proteína)/química
16.
Life Sci ; 295: 120393, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35167880

RESUMO

AIMS: Hyperbaric oxygen (HBO) therapy has been widely used for the adjunctive treatment of diabetic wounds, and is currently known to influence left ventricular (LV) function. However, morphological and molecular repercussions of the HBO in the diabetic myocardium remain to be described. We aimed to investigate whether HBO therapy would mitigate adverse LV remodeling caused by streptozotocin (STZ)-induced diabetes. MAIN METHODS: Sixty-day-old Male Wistar rats were divided into four groups: Control (n = 8), HBO (n = 7), STZ (n = 10), and STZ + HBO (n = 8). Diabetes was induced by a single STZ injection (60 mg/kg, i.p.). HBO treatment (100% oxygen at 2.5 atmospheres absolute, 60 min/day, 5 days/week) lasted for 5 weeks. LV morphology was evaluated using histomorphometry. Gene expression analyzes were performed for LV collagens I (Col1a1) and III (Col3a1), matrix metalloproteinases 2 (Mmp2) and 9 (Mmp9), and transforming growth factor-ß1 (Tgfb1). The Immunoexpression of cardiac tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) were also quantified. KEY FINDINGS: HBO therapy prevented LV concentric remodeling, heterogeneous myocyte hypertrophy, and fibrosis in diabetic rats associated with attenuation of leukocyte infiltration. HBO therapy also increased Mmp2 gene expression, and inhibited the induction of Tgfb1 and Mmp9 mRNAs caused by diabetes, and normalized TNF-α and VEGF protein expression. SIGNIFICANCE: HBO therapy had protective effects for the LV structure in STZ-diabetic rats and ameliorated expression levels of genes involved in cardiac collagen turnover, as well as pro-inflammatory and pro-angiogenic signaling.


Assuntos
Oxigenoterapia Hiperbárica/métodos , Remodelação Ventricular/fisiologia , Animais , Cardiotônicos/farmacologia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/fisiopatologia , Fibrose , Ventrículos do Coração/metabolismo , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Miocárdio/metabolismo , Ratos , Ratos Wistar , Estreptozocina/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Função Ventricular Esquerda/efeitos dos fármacos
17.
Nat Prod Res ; : 1-8, 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35045773

RESUMO

A new nor-ent-kaurene diterpene and ten other compounds were isolated from Annona vepretorum stems, including four kaurene diterpenes, three alkamides, one sesquiterpene and two steroids. Their chemical structures were elucidated using spectroscopic methods, including 1D-, 2D-NMR, and HRESIMS. The absolute configuration of compounds 1, 5, 8, 9 and 10 was confirmed by CD experiments. Compounds 1-5 and 8-10 were evaluated for cytotoxic activity using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT method, against three human carcinoma cell lines: human colon (HCT-116), glioblastoma (SF295) and prostate (PC3). However, all isolated compounds exhibited low cytotoxic activity.

18.
Biol Trace Elem Res ; 2022 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-35084633

RESUMO

This study aimed to evaluate the influence of sodium monensin on the hepatic accumulation of copper in sheep. Twenty-four Santa Inês crossbred sheep were used and allocated in a 2 × 2 factorial experiment with six repetitions and considering the factors dietary copper (basal and high) and supplementation (with and without sodium monensin). Thus, four homogeneous groups were formed: control (basal diet); monensin (Mon), 30 ppm of monensin; copper (Cu), 10 10 mg/kg BW per day of copper; monensin + copper (MonCu). The experimental period lasted 14 weeks. Liver and bile samples were collected at the beginning and end of the experiment to determine mineral element concentrations, and weekly blood samples for biochemical, hematological, and mineral evaluation. Liver copper concentrations at the beginning of the experiment did not vary between groups, while mean liver copper concentrations at the end of the experiment were higher in the MonCu, Cu, and Mon groups when compared to the control. At the end of the study, hepatic copper concentration was influenced by copper (p = 0.0001) and monensin (p = 0.0003) supplementation. Copper-supplemented groups had reduced liver iron contents (p = 0.0287) and increased copper concentrations in bile. The biochemical evaluation showed increased serum GGT and AST activity (p < 0.05) in the Cu and MonCu groups from the eleventh week on compared to the control and Mon groups. The increase in activity of these enzymes was influenced by copper supplementation (p = 0.0340). Monensin interferes positively with the hepatic accumulation of copper and the supplementation of this additive may predispose sheep to copper poisoning.

19.
Sleep Breath ; 26(2): 941-948, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34365593

RESUMO

BACKGROUND: Temporomandibular disorders (TMD) is a collective term that refers to complaints of temporomandibular joint (TMJ) pain, fatigue and/or pain of the craniocervical muscles, limitation of movement of the mandible, and TMJ noises. Sleep bruxism (SB) is a disorder involving rhythmic (phasic) or non-rhythmic (tonic) masticatory muscle activity during sleep and is not a movement disorder or a sleep disorder in otherwise healthy individuals. The present study aimed to support or reject the null hypothesis that there is no association between SB and TMD. METHODS: The study population was recruited from patients who visited the Artmedica Clinic, Mossoro city, Rio Grande do Norte, Brazil. Patients who underwent polysomnography received information about the research and were invited to participate following the inclusion and exclusion criteria. The study sample consisted of 40 individuals with age ranging from 19 to 76 years. The subjects were administered the questionnaire of the European Academy of Craniomandibular Disorders (AEDC). Those who answered affirmatively to at least one question of the questionnaire were recommended to visit the primary researcher's dental clinic for examination; those who met the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) were evaluated, and their condition was classified into one or more subtypes of TMD. The subjects were divided into 4 groups according to the polysomnographic findings and the responses to the AEDC questionnaire. Of the 40 individuals who answered the AEDC questionnaire and underwent polysomnography, 28 presented with TMD symptoms. The data were expressed as simple frequency and percentage values using statistical software. Values of p < 0.05 were considered to be significant. RESULTS: The results showed that the frequency of TMD in individuals diagnosed to have SB was 46.4%. According to the DC/TMD of the 28 individuals, the most prevalent TMD subtype was local myalgia (85.7%). Of the total subjects, 32.5% had TMD and SB, 36.4% were males, and in the age range of 31 to 40 years (40%). CONCLUSION: In this study sample, there was no association between SB as currently defined and TMD, thus confirming previous findings on this topic.


Assuntos
Bruxismo do Sono , Transtornos da Articulação Temporomandibular , Adulto , Idoso , Estudos de Casos e Controles , Dor Facial , Feminino , Humanos , Masculino , Músculos da Mastigação , Pessoa de Meia-Idade , Bruxismo do Sono/diagnóstico , Transtornos da Articulação Temporomandibular/diagnóstico , Transtornos da Articulação Temporomandibular/epidemiologia , Adulto Jovem
20.
Rev. bras. epidemiol ; 25: e220017, 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1387825

RESUMO

ABSTRACT: Objective: To describe the performance of Primary Health Care, according to conglomerates of São Paulo cities that present homogeneous indicators. Methods: This is a descriptive study, based on secondary data extracted from official sources of the Unified Health System, for the year 2018. An analysis matrix was created, with the proposition of performance (access, effectiveness and adequacy) and context indicators (population, health determinants and financing) selected and organized in dimensions and sub-dimensions. Cluster Analysis was used to identify the groups of homogeneous municipalities. Results: 645 municipalities were divided in 6 conglomerates. Clusters 2 and 3 were formed predominantly by small municipalities with greater access to health; cluster 3 has less social vulnerability and greater investment in health. Clusters 1, 4 and 5 were formed by the largest municipalities with less access to health; cluster 4 presents greater social vulnerability, less coverage of private health plans and a greater percentage of health resources; cluster 5 was characterized by greater Gross Domestic Product per capita and greater coverage of private health plans. Cluster 6, formed by the city of São Paulo, was a particular case. Cluster 2 drew attention, as it was shown to have increased coverage, but signaled lower efficacy and adequacy levels. Cluster 3 had the best performance among all clusters. Conclusion: These findings can support regional and municipal management, given the complexity of the territory of São Paulo, pointing to scenarios that demand broader public management initiatives.


RESUMO: Objetivo: Descrever o desempenho da atenção primária à saúde, segundo clusters de municípios paulistas que apresentaram indicadores homogêneos. Métodos: Trata-se de um estudo descritivo, com base em dados secundários extraídos de fontes oficiais do Sistema Único de Saúde, referentes ao ano de 2018. Foi elaborada uma matriz de análise, com a proposição de indicadores de desempenho (acesso, efetividade e adequação) e contexto (população, determinantes de saúde e financiamento), selecionados e organizados em dimensões e subdimensões. Para identificar os grupos de municípios homogêneos, foi utilizada a análise de cluster Resultados: Dos 645 municípios, constituíram-se seis clusters. Os clusters 2 e 3 foram formados, predominantemente, por municípios pequenos e com maior acesso; entre eles, o cluster 3 apresentou menor vulnerabilidade social e maior investimento em saúde. Os clusters 1, 4 e 5, em contrapartida, foram formados por municípios maiores e com menor acesso; entre eles, o cluster 4 apresentou maior vulnerabilidade social, menor cobertura de planos privados de saúde e maior percentual de recursos utilizados em saúde; e o cluster 5, maior produto interno bruto per capita e maior cobertura de planos privados de saúde. O cluster 6, formado pelo município de São Paulo, demonstrou ser um caso particular. Ainda, o cluster 2 chamou atenção. Apresentando maior cobertura, sinalizou menor efetividade e adequação. Entre todos os clusters, o cluster 3 alcançou o melhor desempenho. Conclusão: Os resultados podem subsidiar a gestão regional e municipal, diante da complexidade do território paulista, apontando para cenários que demandam maiores inciativas de gestão pública.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...