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1.
Int Endod J ; 57(8): 1099-1109, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38581182

RESUMO

AIM: This prospective cohort study was undertaken to evaluate the success rate of root canal treatment (RCT) in type 2 diabetes mellitus (T2DM) patients with targeted level and unachieved targeted level of glycaemic control as well as the impact of RCT on the glucose blood level in T2DM patients. METHODOLOGY: Patients needing RCT were divided into three groups: these without T2DM, that is, the control group (CG), those with targeted level of glycated haemoglobin HbA1c < 7% (TL A1c) and the third ones with unachieved targeted level (UTL A1c), that is, with HbA1c ≥ 7%. Before RCT, HbA1c and the periapical index (PAI) score were assessed, as well as 1 year later. RESULTS: Our results showed less favourable treatment results of RCT such as a reduction of radiographic lesions in T2DM patients, particularly in subjects with UTL A1c. The intergroup analysis of PAI score at the 12-month follow-up revealed a significant difference in TL A1C (p = .022) and CG (p = .001) with respect to UTL A1c. Total number of healed teeth (PAI≤2) at the 12-month after RCT in UTL A1c was significantly lower in comparison to CG (p = .008). Contrariwise, RCT may improve the glycaemic control in diabetic patients with UTL A1c after 12 months of posttreatment. Regression analysis showed that UTL A1c patients were more likely to have AP persistence after endodontic treatment (OR = 4.788; CI: 1.157-19.816; p = .031). CONCLUSIONS: T2DM retards the AP healing and conversely AP contributes to increasing the inflammatory burden in T2DM. RCT reduces the cumulative inflammatory burden in T2DM and thus may contribute to improvement of glycaemic control particularly in patients with UTL A1c.


Assuntos
Diabetes Mellitus Tipo 2 , Hemoglobinas Glicadas , Hiperglicemia , Periodontite Periapical , Tratamento do Canal Radicular , Humanos , Periodontite Periapical/terapia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/sangue , Estudos Prospectivos , Tratamento do Canal Radicular/métodos , Masculino , Pessoa de Meia-Idade , Hemoglobinas Glicadas/análise , Feminino , Hiperglicemia/sangue , Hiperglicemia/complicações , Adulto , Resultado do Tratamento , Glicemia/análise , Idoso
2.
Int J Mol Sci ; 25(10)2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38791205

RESUMO

Microglia are key players in the brain's innate immune response, contributing to homeostatic and reparative functions but also to inflammatory and underlying mechanisms of neurodegeneration. Targeting microglia and modulating their function may have therapeutic potential for mitigating neuroinflammation and neurodegeneration. The anti-inflammatory properties of essential oils suggest that some of their components may be useful in regulating microglial function and microglial-associated neuroinflammation. This study, starting from the ethnopharmacological premises of the therapeutic benefits of aromatic plants, assessed the evidence for the essential oil modulation of microglia, investigating their potential pharmacological mechanisms. Current knowledge of the phytoconstituents, safety of essential oil components, and anti-inflammatory and potential neuroprotective effects were reviewed. This review encompasses essential oils of Thymus spp., Artemisia spp., Ziziphora clinopodioides, Valeriana jatamansi, Acorus spp., and others as well as some of their components including 1,8-cineole, ß-caryophyllene, ß-patchoulene, carvacrol, ß-ionone, eugenol, geraniol, menthol, linalool, thymol, α-asarone, and α-thujone. Essential oils that target PPAR/PI3K-Akt/MAPK signalling pathways could supplement other approaches to modulate microglial-associated inflammation to treat neurodegenerative diseases, particularly in cases where reactive microglia play a part in the pathophysiological mechanisms underlying neurodegeneration.


Assuntos
Anti-Inflamatórios , Microglia , Fármacos Neuroprotetores , Óleos Voláteis , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Microglia/efeitos dos fármacos , Microglia/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Humanos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Animais
3.
Int J Mol Sci ; 25(2)2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38256015

RESUMO

This study aimed to evaluate the protective action of oregano (Origanum vulgare) essential oil and its monoterpene constituents (thymol and carvacrol) in L-arginine-induced kidney damage by studying inflammatory and tissue damage parameters. The determination of biochemical markers that reflect kidney function, i.e., serum levels of urea and creatinine, tissue levels of neutrophil-gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1), as well as a panel of oxidative-stress-related and inflammatory biomarkers, was performed. Furthermore, histopathological and immunohistochemical analyses of kidneys obtained from different experimental groups were conducted. Pre-treatment with the investigated compounds prevented an L-arginine-induced increase in serum and tissue kidney damage markers and, additionally, decreased the levels of inflammation-related parameters (TNF-α and nitric oxide concentrations and myeloperoxidase activity). Micromorphological kidney tissue changes correlate with the alterations observed in the biochemical parameters, as well as the expression of CD95 in tubule cells and CD68 in inflammatory infiltrate cells. The present results revealed that oregano essential oil, thymol, and carvacrol exert nephroprotective activity, which could be, to a great extent, associated with their anti-inflammatory, antiradical scavenging, and antiapoptotic action and, above all, due to their ability to lessen the disturbances arising from acute pancreatic damage. Further in-depth studies are needed in order to provide more detailed explanations of the observed activities.


Assuntos
Cimenos , Óleos Voláteis , Origanum , Animais , Ratos , Óleos Voláteis/farmacologia , Timol/farmacologia , Rim , Inflamação/tratamento farmacológico , Arginina/farmacologia
4.
Int J Mol Sci ; 25(8)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38674081

RESUMO

Marrubiin is a diterpene with a long history of a wide range of biological activities. In this study, the anti-inflammatory effects of marrubiin were investigated using several in vitro and in vivo assays. Marrubiin inhibited carrageenan-induced peritoneal inflammation by preventing inflammatory cell infiltration and peritoneal mast cell degranulation. The anti-inflammatory activity was further demonstrated by monitoring a set of biochemical parameters, showing that the peritoneal fluid of animals treated with marrubiin had lower levels of proteins and lower myeloperoxidase activity compared with the fluid of animals that were not treated. Marrubiin exerted the most pronounced cytotoxic activity towards peripheral mononuclear cells, being the main contributors to peritoneal inflammation. Additionally, a moderate lipoxygenase inhibition activity of marrubiin was observed.


Assuntos
Anti-Inflamatórios , Carragenina , Diterpenos , Mastócitos , Animais , Carragenina/efeitos adversos , Camundongos , Diterpenos/farmacologia , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Anti-Inflamatórios/farmacologia , Camundongos Endogâmicos C57BL , Peritonite/induzido quimicamente , Peritonite/tratamento farmacológico , Peritonite/metabolismo , Peritonite/patologia , Masculino , Inflamação/metabolismo , Inflamação/tratamento farmacológico , Inflamação/induzido quimicamente , Inflamação/patologia , Degranulação Celular/efeitos dos fármacos , Peroxidase/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo
5.
Int J Mol Sci ; 25(6)2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38542287

RESUMO

The encounter between dental biofilm and neutrophils in periodontitis remains elusive, although it apparently plays a crucial role in the periodontal pathology and constitutes a key topic of periodontology. Dental biofilm and neutrophils were isolated from orally healthy persons and patients with periodontitis. We investigated biofilm and its particle-shedding phenomenon with electron microscopy and nanoparticle tracking analysis (NTA); biofilm shedding-neutrophil interactions were examined ex vivo with epi-fluorescence microscopy. For this purpose, we used acellular dental biofilm shedding, purified lipopolysaccharide (LPS), and phorbol 12-myristate 13-acetate (PMA) as activators, and the interleukin 8 receptor beta (CXCR2) inhibitor and the anti-interleukin 8 receptor alpha (CXCR1) antibody as modulators. The shedding of acellular dental biofilms overwhelmingly consists of bacterial extracellular vesicles (BEVs). The latter induced the moderate formation of neutrophil extracellular traps (NETs) in orally healthy subjects and a strong formation in patients with periodontitis. A CXCR2 inhibitor and an anti-CXCR1 antibody had a minor effect on NET formation. Neutrophils from patients with periodontitis exhibited NET hyper-responsiveness. BEVs were stronger inducers of NET formation than purified LPS and PMA. A plateau of neutrophil responsiveness is reached above the age of 40 years, indicating the abrupt switch of maladaptive trained immunity (TI) into the activated modus. Our results suggest that dental biofilms consist of and disseminate immense amounts of outer membrane vesicles (OMVs), which initiate NET formation via a non-canonical cytosolic LPS/caspase-4/11/Gasdermin D pathway. This modus of NET formation is independent of neutrophil elastase (NE), myeloperoxidase (MPO), peptidylarginine deiminase 4 (PAD4), and toll-like receptors (TLR). In periodontitis, the hyper-responsiveness of neutrophils to BEVs and the increased NET formation appear to be a consequence of TI.


Assuntos
Armadilhas Extracelulares , Periodontite , Humanos , Adulto , Neutrófilos/metabolismo , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo , Armadilhas Extracelulares/metabolismo , Periodontite/metabolismo , Biofilmes
6.
Medicina (Kaunas) ; 59(8)2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37629756

RESUMO

Post-traumatic stress disorder (PTSD) is a prevalent psychiatric disorder that often occurs following war trauma. Despite its high prevalence, there is still a lack of comprehensive understanding regarding the mechanisms underlying its progression and treatment resistance. Recent research has shed light on the biological basis of PTSD, with neuroimaging studies revealing altered brain connectivity patterns in affected individuals. In war contexts, traumatic brain injury (TBI) is a common occurrence and is associated with a high prevalence of PTSD. This study aimed to compare the severity of PTSD and depression in patients with and without a history of TBI to shed light on the impact of comorbid TBI on the presentation of PTSD symptoms. To achieve this goal, a cross-sectional study was conducted involving a sample of 60 outpatients who were diagnosed with both PTSD and Depressive Disorder. The inclusion criteria required participants to meet the diagnostic criteria for both disorders using validated tools. The severities of PTSD and depressive symptoms were assessed using scales that have been widely used and validated in previous research. By utilizing these standardized assessment tools, this study aimed to ensure the reliability and validity of the obtained data. The results of this study revealed that patients with comorbid PTSD and TBI exhibited a significantly higher severity of PTSD symptoms compared to those with PTSD only. Specifically, the comorbid group demonstrated higher ratings of symptom intensity across all symptom clusters. These findings are consistent with previous research that has highlighted the impact of comorbid TBI on the intensity and persistence of PTSD symptoms. When controlling for PTSD severity, no significant differences were observed in the severity of depressive symptoms between the two groups. This suggests that the increased depressive symptoms observed in the comorbid group may be primarily driven by the presence of more intense PTSD symptoms rather than TBI per se. The findings highlight the need for an accurate diagnosis of TBI in individuals with PTSD to guide appropriate treatment interventions. Further research is warranted to delve into the underlying mechanisms that contribute to the interaction between TBI and PTSD and to develop targeted interventions for individuals with comorbid PTSD and TBI.


Assuntos
Lesões Encefálicas Traumáticas , Transtornos de Estresse Pós-Traumáticos , Humanos , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Estudos Transversais , Depressão/complicações , Depressão/epidemiologia , Reprodutibilidade dos Testes , Lesões Encefálicas Traumáticas/complicações
7.
Chem Biodivers ; 19(1): e202100724, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34773377

RESUMO

To complement the knowledge on the anti-inflammatory activity of methyl and isopropyl N-methylanthranilates, two natural products with panacea-like properties, we investigated their effects on thioglycolate-elicited macrophages by evaluating macrophage ability to metabolize MTT, macrophage membrane function, and macrophage myeloperoxidase and phagocytic activities. Moreover, two additional aspects of the inflammatory response of these compounds, their inhibitory activity on xanthine oxidase and catalase, were studied. It was found that these two compounds regulate elicited macrophage functions, most probably by interfering with the function of cell membranes and changing the reducing cellular capacity or enzyme activity of macrophages. Nonetheless, no significant inhibitory action either towards xanthine oxidase or catalase was found, suggesting that the inhibition of these enzymes is not involved in the anti-inflammatory mode of action of these two esters.


Assuntos
Fagocitose/efeitos dos fármacos , ortoaminobenzoatos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Catalase/antagonistas & inibidores , Catalase/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Macrófagos/citologia , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Peroxidase/metabolismo , Ratos , Ratos Wistar , Xantina Oxidase/antagonistas & inibidores , Xantina Oxidase/metabolismo , ortoaminobenzoatos/química , ortoaminobenzoatos/metabolismo
8.
Medicina (Kaunas) ; 58(11)2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36422225

RESUMO

The massive expansion of the new coronavirus SARS-CoV-2 has urged countries to introduce lockdowns and set restrictive actions worldwide. The focus of the studies was to determine how COVID-19 induces damage to the lungs in order to find an alternative or adjuvant therapy that could lead to preventing COVID-19 or at least ameliorating it. This paper aims to survey the literature and provide new insights into behavioral and dietary habits that could influence the prevention of COVID-19. Maintaining an adequate mental health status, sleep, and taking moderate exercise are often disrupted in the conditions of lockdown and are followed by weakened immunity. Mediterranean and vegetarian diets are superior to other eating patterns in terms of immunity boosting and fighting COVID-19. Our study showed how adequate hydration, green tea intake, and supplementation with vitamins D, C, and E can increase our chances of avoiding the infection and even help us sleep better. Another focus of the research was on determining what level of hygiene really increases one's chances of not contracting SARS-CoV-2, but this seems a little counter-intuitive at first. Since an immunocompromised state is a familiar predisposing factor for all contagious diseases, maintaining healthy behavioral and dietary habits could be a crucial step in boosting immunity and preventing COVID-19.


Assuntos
COVID-19 , Doenças não Transmissíveis , Humanos , SARS-CoV-2 , Controle de Doenças Transmissíveis , Comportamento Alimentar , Doenças não Transmissíveis/prevenção & controle , Civilização
9.
Opt Express ; 29(21): 32739-32754, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34809098

RESUMO

A fast and robust, yet simple, method has been developed for the immediate characterization of x-ray pulse durations via IR/THz streaking that uses the center of energy (COE) of the photoelectron spectrum for the evaluation. The manuscript presents theory and numerical models demonstrating that the maximum COEs shift as a function of the pulse duration and compares them to existing data for validation. It further establishes that the maximum COE can be derived from two COE measurements set at a phase of π/2 apart. The theory, model, and data agree with each other very well, and they present a way to measure pulse durations ranging from sub-fs to tens of fs on-the-fly with a fairly simple experimental setup.

10.
Can J Physiol Pharmacol ; 99(2): 185-191, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33509026

RESUMO

Doxorubicin is an anticancer agent that is commonly used to treat a number of tumors and is associated with acute and chronic changes of the cardiovascular system. Ellagic acid has strong free radical scavenging capacity, neuroprotective and hepatoprotective effects, and is known to protect against changes occurring due to diabetes, cardiovascular diseases, and cancer. Twenty-four Wistar rats were divided in four groups: control group received saline, doxorubicin group received doxorubicin in a single dose of 20 mg/kg, ellagic acid group received ellagic acid in a dose of 4 mg/kg, and doxorubicin + ellagic acid group received doxorubicin and ellagic acid in same doses as in previous groups. The effect of ellagic acid treatment, alone or in combination with doxorubicin, was studied on isolated heart frequency and strength of the contraction, and on thoracic aorta contractile responses. Application of ellagic acid to rats pre-treated with doxorubicin significantly prevented functional changes occurring in the heart, but not in the thoracic aorta tissue. Ellagic acid statistically significantly (p < 0.001) prevented doxorubicin-induced increase in heart rate, while at the same time increased single contraction force (p < 0.001) and attenuated morphological changes on heart tissue induced by doxorubicin. We can conclude that ellagic acid has potential to prevent doxorubicin-induced changes of the cardiovascular system.


Assuntos
Doxorrubicina/efeitos adversos , Ácido Elágico/farmacologia , Coração/efeitos dos fármacos , Animais , Citoproteção/efeitos dos fármacos , Relação Dose-Resposta a Droga , Masculino , Ratos , Ratos Wistar
11.
Can J Physiol Pharmacol ; 99(1): 110-114, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33449845

RESUMO

Oleuropein (OLE) is the main bioactive ingredient in the leaves of the olive plant Olea europaea L. (Oleaceae), which has proven beneficial due to the antiinflammatory, antiatherogenic, anticancer, antimicrobial, and antiviral effects. This study aimed to investigate the antihypertensive and vasodilator potential of OLE by analyzing its acute effects on spontaneous atrial contractions and vasomotor responses of the isolated thoracic aorta in rats. We showed that the application of OLE induces negative chronotropic and inotropic effects on the heart. OLE also causes mild aortic vasodilation given that the maximal reduction in tension of intact aortic rings precontracted with phenylephrine was approximately 30%. This vasodilation is likely dependent on the nitric oxide released from the endothelium based on the effect obtained on denuded and phenylephrine precontracted aortic rings and responses reordered following vasoconstriction induced by high concentrations of K+ and heparin. Our findings provide a basis for further testing of OLE cardiovascular effects, which may lead to subsequent clinical research for its application in the treatment of hypertension and heart disease.


Assuntos
Anti-Hipertensivos/farmacologia , Endotélio Vascular/efeitos dos fármacos , Átrios do Coração/efeitos dos fármacos , Glucosídeos Iridoides/farmacologia , Vasodilatadores/administração & dosagem , Animais , Anti-Hipertensivos/uso terapêutico , Aorta Torácica/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Endotélio Vascular/metabolismo , Átrios do Coração/metabolismo , Humanos , Hipertensão/tratamento farmacológico , Glucosídeos Iridoides/uso terapêutico , Masculino , Modelos Animais , Óxido Nítrico/metabolismo , Oleaceae/química , Folhas de Planta/química , Ratos , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos
12.
Eur Addict Res ; 27(1): 67-74, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32172240

RESUMO

BACKGROUND: Besides numerous advantages and commodities offered by smartphones, there are obvious unhealthy effects. The global trend of an increase in the frequency of usage of smartphones, that is, prolonged screen time, is closely related to problematic smartphone use. The aim of our study was to measure the level of problematic smartphone use in a student population through the assessment of the smartphone screen time and the determination of the student chronotype, as well as through the correlation between these variables. METHODS: The participants were students of medicine of both sexes. Problematic smartphone use was measured by the short version of the Smartphone Addiction Scale. Smartphone screen time was assessed by the free Android application Quality Time. Chronotype was established by the Morningness-Eveningness Questionnaire. RESULTS: Almost one quarter (22.7%) of students involved in our study could be classified as being "smartphone-addicted". The students with problematic smartphone use more frequently (statistical significance) belonged to the evening chronotype. Those students spent significantly more time on their phones compared to the non-addicted ones. There was no statistically significant difference between the number of male and female students with problematic smartphone use. The best predictors of problematic smartphone use were longer daily smartphone screen time and evening chronotype personality. CONCLUSIONS: The results of our study showed that a significant number of students of medicine showed problematic smartphone use. There was a strong correlation between extensive screen time and the level of problematic smartphone use in the studied population.


Assuntos
Smartphone , Universidades , Feminino , Humanos , Masculino , Tempo de Tela , Estudantes , Inquéritos e Questionários
13.
J Oral Rehabil ; 48(2): 124-131, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33064877

RESUMO

BACKGROUND: Menstrual cycle may contribute to experimental pain measures in healthy women and women with chronic pain. OBJECTIVES: The present study aimed to investigate variation in pulp sensitivity across the menstrual cycle in healthy women and women with temporomandibular disorders (TMD) and to explore the effect of TMD pain and psychosocial variables on the pulp response. METHODS: This longitudinal study involved 47 regularly menstruating women aged 20-45, 24 healthy and 23 with diagnosed painful TMD. The electric and cold stimuli were performed by electric pulp tester and refrigerant spray, respectively, on mandibular lateral incisors, in five menstrual phases (menstrual, follicular, periovulatory, luteal and premenstrual). Research Diagnostic Criteria for TMD were used to assess TMD, chronic pain, depression and somatisation. Regression analysis was performed to investigate the effect of the predictor variables on the pulp sensitivity. RESULTS: Significant phase-related differences were observed for pain intensity to cold stimuli. Higher pain sensitivity was reported in menstrual in comparison with luteal phase (P = .019) among healthy women, and in menstrual in comparison with follicular (P = .033), periovulatory (P = .003) and luteal (P = .007) phases in TMD women. No significant differences were recorded for electric stimuli. Regression analysis identified depression as the determinant of cold and electric response in menstrual phase, regardless of age and presence of TMD. CONCLUSION: Menstrual phase in healthy and TMD women with regular menstrual cycle is characterised with higher pulp sensitivity to cold stimuli. Depressive symptoms independently influence pulp response in this phase.


Assuntos
Limiar da Dor , Transtornos da Articulação Temporomandibular , Adulto , Feminino , Humanos , Estudos Longitudinais , Ciclo Menstrual , Pessoa de Meia-Idade , Medição da Dor , Adulto Jovem
14.
Opt Express ; 28(14): 20686-20703, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32680123

RESUMO

The THz-field-driven streak camera has proven to be a powerful diagnostic-technique that enables the shot-to-shot characterization of the duration and the arrival time jitter of free electron laser (FEL) pulses. Here we investigate the performance of three computational approaches capable to determine the duration of FEL pulses with complex temporal structures from single-shot measurements of up to three simultaneously recorded spectra. We use numerically simulated FEL pulses in order to validate the accuracy of the pulse length retrieval in average as well as in a single-shot mode. We discuss requirements for the THz field strength in order to achieve reliable results and compare our numerical study with the analysis of experimental data that were obtained at the FEL in Hamburg - FLASH.

15.
J Nat Prod ; 83(10): 2902-2914, 2020 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-33030341

RESUMO

In this investigation, chromatographic separations of the diethyl ether extracts of two European annual Bupleurum taxa, B. praealtum and B. veronense, yielded nine new natural products, namely, a series of esters of stereoisomeric tetradeca-5,7,9,11-tetraen-1-ols (1-4 and 8), a tetra-unsaturated γ-tetradecalactone (5), a dibenzylbutyrolactone lignan (7-oxoarcitin, 6), a falcarinol-related 17-membered macrolide (7) possessing a conjugated diyne-system, and an acylphloroglucinol derivative (9). All these new compounds were fully characterized by NMR, IR, UV, MS, and optical rotation measurement, including 1H NMR full spin spectral simulation, whereas the absolute configurations of 1, 5, and 9 were determined via chemical correlations and NMR analysis of Mosher esters. The in vitro potential immunomodulatory activities of 1, 4, 5, and (+)-arcitin were assessed by determining their effects on the functional properties of isolated rat splenocytes and peritoneal macrophages. The results obtained support the known immunomodulatory ethnomedicinal usage of Bupleurum species.


Assuntos
Produtos Biológicos/farmacologia , Bupleurum/química , Fatores Imunológicos/farmacologia , Animais , Ratos
16.
J Nat Prod ; 83(12): 3554-3563, 2020 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-33264011

RESUMO

Structural elucidation of three new sesquiterpenoids, namely, (1Z,4E)-lepidoza-1(10),4-dien-14-ol (1), rel-(1(10)Z,4S,5E,7R)-germacra-1(10),6 diene-11,14-diol (2), and rel-(1(10)Z,4S,5E,7R)-humula-1(10),5-diene-7,14-diol (3), isolated from the liverwort Conocephalum conicum, was accomplished by a combination of extensive NMR experiments, 1H NMR simulation, and other means. Additionally, the change of the identity of bicyclogermacren-14-al, previously reported as a C. conicum constituent, to isolepidozen-14-al is proposed. Compounds 2 and 3 appear to be related to 1 via hydration involving a shared intermediate, a substituted cyclopropylmethyl cation, formed by a highly regio- and stereoselective protonation of 1, followed by a stereospecific fission of the three-membered ring. In other words, an isolepidozene derivative might be a branchpoint to humulanes and germacranes; this transformation could be of, up to now, unknown, biosynthetic and/or synthetic relevance. Multivariate statistical analysis of the compositional data of C. conicum extract constituents was used to probe the hypothesized biochemical relations. The immunomodulatory effect of 1-3 and conocephalenol (4) was evaluated in an in vitro model on both nonstimulated and mitogen-stimulated rat splenocytes. The compounds displayed varying degrees of cytotoxicity to nonstimulated splenocytes, whereas 2 and 3 were found to exert immunosuppressive effects on concanavalin A-stimulated splenocytes while not being cytotoxic at the same concentrations.


Assuntos
Adjuvantes Imunológicos/farmacologia , Hepatófitas/química , Sesquiterpenos de Germacrano/farmacologia , Adjuvantes Imunológicos/química , Estrutura Molecular , Sesquiterpenos de Germacrano/química
17.
Can J Physiol Pharmacol ; 98(2): 117-123, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31995714

RESUMO

Since cisplatin-induced nephrotoxicity has very important clinical consequences, the purpose of this study was to determine the potential protective effect of aminoguanidine on the acute kidney injury caused by cisplatin. Experiments were done on 40 Wistar rats divided into four groups. The CIS group received cisplatin in a single dose of 8 mg/kg, while the CISAG group received the same dose of cisplatin and aminoguanidine (100 mg/kg) by intraperitoneal injections. Animals in the AG group received only aminoguanidine (100 mg/kg) and those in the C group received saline. Quantitative evaluation of structural and functional alterations in the kidneys was performed by analysis of biochemical and parameters of oxidative stress and by histological and morphometric analysis of renal sections. Histological sections of kidney showed structural damage of proximal tubules and glomeruli that were induced by cisplatin. Morphometric analysis revealed statistically significant differences in the area of proximal tubules and the size and cellularity of glomeruli between the CIS and CISAG groups. Glomerular basement membrane thickness was increased in the CIS group, while aminoguanidine attenuated these changes in the CISAG group of rats. Our results suggest that aminoguanidine acts protectively and repairs structural and functional damage of kidney by engaging the existent antioxidative potential at the level of renal tissue.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/patologia , Cisplatino/efeitos adversos , Guanidinas/farmacologia , Rim/efeitos dos fármacos , Rim/patologia , Injúria Renal Aguda/tratamento farmacológico , Animais , Catalase/metabolismo , Guanidinas/uso terapêutico , Rim/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Ratos Wistar
18.
Can J Physiol Pharmacol ; 98(2): 111-116, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31369713

RESUMO

Lycopene is one of the most potent antioxidants among carotenoids due to its ability to quench singlet oxygen and react with free radicals to reduce DNA damage. Methotrexate is widely used in the treatment of several types of cancers and autoimmune diseases. One of the most common side effects of a high-dose of methotrexate is kidney injury. In this study, we evaluated effects of lycopene on the Madin-Darby canine kidney cells (MDCK) treated with methotrexate through the estimation of their mitochondrial and lysosomal functions ((4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide reduction assay and neutral red uptake assay) and changes in cell oxidative status (determination of advanced oxidized proteins concentrations and reduced glutathione levels) and lysosomal enzymes activity (ß-N-acetyl glucosaminidase activity). Results of our study showed that lycopene applied in high concentration caused significant impairment of the MDCK function leading to cell death. Contrarily, in relatively low concentrations lycopene moderately ameliorated methotrexate-induced MDCK cell death estimated by both biochemical and microscopic analyses. It also prevented a significant decline in the MDCK cell lysosomal function estimated by neutral red accumulation ability and activity of the lysosomal enzyme ß-N-acetyl glucosaminidase.


Assuntos
Licopeno/farmacologia , Metotrexato/farmacologia , Animais , Cães , Relação Dose-Resposta a Droga , Lisossomos/efeitos dos fármacos , Lisossomos/enzimologia , Células Madin Darby de Rim Canino , Vermelho Neutro/metabolismo , Estresse Oxidativo/efeitos dos fármacos
19.
Chem Biodivers ; 17(6): e2000206, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32302446

RESUMO

In this work, we explored the possible polypharmacological potential of the already established antimicrobials against gastrointestinal pathogens, 4-(alkylamino)-3-nitrocoumarins, as antianxiety agents, using a battery of in vivo experiments. Three chosen coumarin derivatives, differing in the substituent (sec-butylamino, hexadecylamino, or benzylamino) at position 4, at the doses of 25, 50 and 100 mg kg-1 , were evaluated in light/dark, open-field, horizontal wire and diazepam-induced sleep models using male BALB/c mice. Depending on the applied dose, all three tested coumarins displayed a noteworthy anxiolytic-like effect. 4-(sec-Butylamino)-3-nitro-2H-chromen-2-one and 4-(hexadecylamino)-3-nitro-2H-chromen-2-one could be recognized as true anxiolytics in the lowest applied dose, based on three tests, without exerting any sedative effects. Thus, the 3-nitrocoumarin core deserves further chemical diversity exploration in the 'antianxiety' direction.


Assuntos
Ansiolíticos/química , Cumarínicos/química , Animais , Ansiolíticos/farmacologia , Ansiolíticos/uso terapêutico , Ansiedade/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Cumarínicos/farmacologia , Cumarínicos/uso terapêutico , Diazepam/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Sono/efeitos dos fármacos
20.
Medicina (Kaunas) ; 56(4)2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32316090

RESUMO

Background and objectives: A long-term therapeutic strategy in hypertensive patients equally depends on measured arterial blood pressure values and total determined cardiovascular risk. The aim of the adequate hypertensive patient treatment is both the reduction in arterial blood pressure and the reduction of all preexisting modifiable risk factors, prevention of target organs damage, and adverse cardiovascular events. The aim of this study was to determine independent predictors of cardiovascular events in patients with hypertension and high cardiovascular (CV) risk, and whether the modifiable risk factors could affect long-term prognosis in the studied population. Materials and Methods: This prospective study included 142 hypertensive patients (65% females), mean age 63.1±8 years, with high CV risk. Each participant was followed for 6.2 years. Results: During the follow-up period, the incidence of non-fatal and fatal CV events was 19.7%, CV mortality 7%, and total mortality 9.9%. Our multivariate analysis showed that plaques in both carotid arteries (p = 0.042), diabetes mellitus (p = 0.042) and cholesterol at the beginning of the study (p = 0.016) were significantly associated with an increased risk of CV events. Patients' age (p = 0.009), intima-media thickness (p = 0.001) and diabetes mellitus (p = 0.042) were significantly associated with an increased risk of CV mortality, and age (p = 0.007) and cholesterol (p = 0.002) were independent variables significantly associated with increased total mortality rates. Conclusions: The results of the present study showed that the main predictors of adverse CV events in high-risk hypertensive patients were years of age, cholesterol levels, diabetes, intima-media thickness, and carotid arteries plaques.


Assuntos
Fatores de Risco de Doenças Cardíacas , Hipertensão/classificação , Doenças Cardiovasculares/epidemiologia , Feminino , Humanos , Hipertensão/terapia , Estudos Longitudinais , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco
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