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Temperature is a global factor that affects the performance of all intracellular networks. Robustness against temperature variations is thus expected to be an essential network property, particularly in organisms without inherent temperature control. Here, we combine experimental analyses with computational modeling to investigate thermal robustness of signaling in chemotaxis of Escherichia coli, a relatively simple and well-established model for systems biology. We show that steady-state and kinetic pathway parameters that are essential for chemotactic performance are indeed temperature-compensated in the entire physiological range. Thermal robustness of steady-state pathway output is ensured at several levels by mutual compensation of temperature effects on activities of individual pathway components. Moreover, the effect of temperature on adaptation kinetics is counterbalanced by preprogrammed temperature dependence of enzyme synthesis and stability to achieve nearly optimal performance at the growth temperature. Similar compensatory mechanisms are expected to ensure thermal robustness in other systems.
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Quimiotaxia , Escherichia coli/fisiologia , Transdução de Sinais , Adaptação Fisiológica , Escherichia coli/enzimologia , Transferência Ressonante de Energia de Fluorescência , Cinética , Metilação , Monoéster Fosfórico Hidrolases/metabolismo , Fosfotransferases/metabolismo , TemperaturaRESUMO
INTRODUCTION: The effects of combustible cigarettes (CCs) and electronic nicotine delivery systems (ENDS) on immune cell-driven colon inflammation and intestinal healing of patients with ulcerative colitis (UC) are still unknown and, therefore, were examined in this study. METHODS: Intracellular staining and flow cytometry analysis of immune cells isolated from UC patients who used ENDS (UCENDS), CCs (UCCC) and who were non-smokers (UCAIR) were performed to elucidate cellular mechanisms which were responsible for CCs and ENDS-dependent modulation of immune response during UC progression. Additionally, dextran sulfate sodium (DSS)-colitis was induced in ENDS/CC/air-exposed mice (DSSENDS/ DSSCC/DSSAIR groups) to support clinical findings. RESULTS: Significantly increased number of immunosuppressive, IL-10, TGF-ß and IL-35-producing, FoxP3-expressing CD3+CD4+T regulatory cells (Tregs) was observed in the blood of UCENDS patients while reduced presence of inflammatory, TNF-α and IFN-γ-producing, Tbx21-expressing CD3+CD4+ Th1, IL-4-producing Gata3-expresing Th2 and IL-17, IL-22-producing, RORγT, IL-23R-expressing Th17 cells were noticed in the blood of UCCC patients. Exposure to either CCs or ENDS was associated with enhanced mucosal healing, ameliorated spontaneous recovery and improved survival of DSS-treated mice. An expansion of immunosuppressive cells (IL-10-producing tolerogenic CD11c+ dendritic cells, alternatively activated CD206, Arginase 1-expressing, IL-10-producing F4/80+macrophages, IL-10-producing FoxP3-expressing Tregs) was noticed in the colons of DSSENDS-treated mice, while reduced number of inflammatory, IL-17- and IL-4-producing T lymphocytes was observed in the colons of DSSCC-compared to DSSAIR-treated mice. CONCLUSIONS: Despite different mechanisms of action, both ENDS and CCs attenuated on-going colon inflammation, enhanced healing and ameliorated recovery of injured intestines of DSS-treated mice and UC patients. IMPLICATIONS: This is the first study that compared the effects of CCs and ENDS on immune cells of patients suffering from ulcerative colitis, providing new information about molecular and cellular mechanisms which were responsible for ENDS and CCs-dependent modulation of immune cell-driven colon injury and inflammation. Obtained results showed that both ENDS and CCs had capacity to attenuate detrimental immune response, enhanced healing and ameliorated recovery of injured intestines.
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The study included 40 patients of both genders who underwent skin transplantation after a hand injury. The study aims to evaluate the oxidative stress parameters in patients' blood and serum levels of galectin-3 in order to investigate gender differences pre- and post- skin transplantation. The results of the study suggest a significant increase in superoxide anion radical levels, catalase activity, and reduced glutathione levels in females before skin transplantation. The surgical treatment caused significant increase in superoxide anion radical and hydrogen peroxide levels as prooxidants in males, while superoxide dismutase and catalase activity were also increased 7 days after the procedure. In females, superoxide anion radical and TBARS levels increased after surgical procedure as well as the activity of catalase. Regarding galectin-3 levels, a significant interaction between gender and time was observed (gender×time; p=0.000). Correlation analysis of different oxidative stress markers with gal-3 revealed the existence of a significant negative correlation of superoxide anion radical, catalase, and reduced glutathione with gal-3, but only in female patients. It can be concluded that OS as well as galectin-3 play important roles at least in the first 7 days of the postoperative period.
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Catalase , Galectina 3 , Glutationa , Traumatismos da Mão , Estresse Oxidativo , Transplante de Pele , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Proteínas Sanguíneas , Catalase/sangue , Catalase/metabolismo , Galectina 3/sangue , Galectina 3/metabolismo , Galectinas , Glutationa/sangue , Glutationa/metabolismo , Traumatismos da Mão/cirurgia , Traumatismos da Mão/sangue , Traumatismos da Mão/metabolismo , Peróxido de Hidrogênio/sangue , Peróxido de Hidrogênio/metabolismo , Caracteres Sexuais , Fatores Sexuais , Superóxido Dismutase/sangue , Superóxido Dismutase/metabolismo , Superóxidos/metabolismo , Superóxidos/sangue , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
This study aimed to prepare, characterize and assess the antioxidant activity of yellow bedstraw extracts (YBEs), focusing on identifying extracts with high antioxidant capacity. The selected extract was loaded into an oral liquid formulation and further investigated for its therapeutic potential in reducing blood pressure and associated complications in spontaneously hypertensive Wistar kyoto rats (SHR). Rats were divided into untreated SHR and SHR treated with a YBE-based oral formulation over four weeks. After treatment, blood pressure was measured, and cardiac function was assessed using the Langendorff technique to simulate ex vivo ischemic conditions. Prooxidant levels were assessed in plasma while antioxidant activity was evaluated in red blood cells. Histological analyses of heart, kidney, and liver samples were conducted to assess pathological changes induced by hypertension. Our results showed that the oral formulation loaded with ethanol YBE effectively reduced blood pressure, preserved myocardial function under ischemic stress, and decreased oxidative stress markers in blood. Importantly, our formulation with YBE demonstrated potential in attenuating structural kidney damage associated with hypertension. Overall, these findings suggest a cardioprotective effect of orally administered YBE formulation, highlighting its potential as an herbal supplement. However, clinical studies are warranted to validate these findings and explore the extract's suitability for clinical use.
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Anti-Hipertensivos , Antioxidantes , Pressão Sanguínea , Cardiotônicos , Hipertensão , Estresse Oxidativo , Extratos Vegetais , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Extratos Vegetais/administração & dosagem , Ratos , Pressão Sanguínea/efeitos dos fármacos , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/química , Hipertensão/tratamento farmacológico , Masculino , Estresse Oxidativo/efeitos dos fármacos , Cardiotônicos/farmacologia , Antioxidantes/farmacologia , Administração Oral , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologiaRESUMO
The aim of this study was to compare knee extensor and flexor strength recovery following anterior cruciate ligament (ACL) reconstruction between bone-patellar tendon-bone (BPTB) and hamstring tendon (HT) grafts in international male soccer players undergoing comparable 6-month rehabilitation programmes. Seventeen players underwent ACL reconstruction with either an autogenous BPTB graft or HT graft. Knee extensor and flexor peak torques were measured at 3 months and 6 months in the injured and contralateral legs following surgery using isokinetic dynamometry. The moderate-large asymmetries in knee extensor peak torque between legs at 3 months across graft types (BPTB: p = 0.002, g = -0.94; HT: p = 0.02, g = -0.55) were reduced to trivial asymmetries at 6 months (BPTB: p = 0.30, g = -0.19; HT: p = 0.40, g = -0.16), with a non-significant difference in limb symmetry index (LSI) between grafts at 6 months (p = 0.62, g = -0.24). Similarly, moderate-large asymmetries in knee flexor peak torque between legs at 3 months across graft types (BPTB: p = 0.13, g = -0.50; HT: p = 0.01, g = -0.97) were reduced to trivial-small asymmetries at 6 months (BPTB: p = 0.25, g = 0.18; HT: p = 0.01, g = -0.47); however, a superior LSI was evident with BPTB compared to HT grafts at 6 months (p = 0.007, g = 1.43, large). Strength and conditioning professionals working with soccer players who are rehabilitating from ACL reconstruction after receiving a HT graft should give adequate attention to delivering suitable hamstring exercises that ensure optimal strength restoration.
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Coronavirus Disease 2019 (COVID-19) has been ranked among the most fatal infectious diseases worldwide, with host's immune response significantly affecting the prognosis. With an aim to timely predict the most likely outcome of SARS-CoV-2 infection, we investigated the association of IFNL3 and IFNL4 polymorphisms, as well as other potentially relevant factors, with the COVID-19 mortality. This prospective observational case-control study involved 178 COVID-19 patients, hospitalized at Corona Center or Clinic for Infectious Diseases of University Clinical Centre Kragujevac, Serbia, followed up until hospital discharge or in-hospital death. Demographic and clinical data on all participants were retrieved from the electronic medical records, and TaqMan assays were employed in genotyping for IFNL3 and IFNL4 single nucleotide polymorphisms (SNPs), namely rs12980275, rs8099917, rs12979860, and rs368234815. 21.9% and 65.0% of hospitalized and critically ill COVID-19 patients, respectively, died in-hospital. Multivariable logistic regression analysis revealed increased Charlson Comorbidity Index (CCI), N/L, and lactate dehydrogenase (LDH) level to be associated with an increased likelihood of a lethal outcome. Similarly, females and the carriers of at least one variant allele of IFNL3 rs8099917 were almost 36-fold more likely not to survive SARS-CoV-2 infection. On the other hand, the presence of at least one ancestral allele of IFNL4 rs368234815 decreased more than 15-fold the likelihood of mortality from COVID-19. Our results suggest that, in addition to LDH level, N/L ratio, and CCI, IFNL4 rs368234815 and IFNL3 rs8099917 polymorphisms, but also patients' gender, significantly affect the outcome of COVID-19.
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COVID-19 , Interleucinas , Feminino , Humanos , Estudos de Casos e Controles , Genótipo , Mortalidade Hospitalar , Interferons , Interleucinas/genética , Polimorfismo de Nucleotídeo Único , SARS-CoV-2RESUMO
Despite the pivotal role of IFN-λs in the innate immune response, the data on its genetic polymorphism in relation to COVID-19 severity are scarce and contradictory. In the present study, we aimed to determine if the presence of the most frequent functional single nucleotide polymorphisms (SNPs) of the two most important IFN-λs coding genes, namely IFNL3 and IFNL4, alters the likelihood of SARS-CoV-2-infected patients to develop more severe form of the disease. This observational cohort study involved 178 COVID-19 patients hospitalized at the University Clinical Centre Kragujevac, Serbia. Patients' demographics, clinical characteristics, and laboratory parameters were collected at admission. COVID-19 signs and symptoms were assessed during the hospital stay, with the worst condition determining the disease severity. Genotyping for IFNL3 (rs12980275 and rs8099917) and IFNL4 (rs12979860 and rs368234815) SNPs was conducted using TaqMan assays. Our study revealed carriers of IFNL3 and IFNL4 minor alleles to be less likely to progress from mild to moderate COVID-19, that is, to develop COVID-19-related pneumonia. After adjustment for other factors of influence, such as age, sex, and comorbidities, the likelihood of pneumonia development remained significantly associated with IFNL4 polymorphism (odds ratios [ORs] [95% confidence interval (95% CI)]: 0.233 [0.071; 0.761]). When the patients were stratified according to sex, the protective role of IFNL4 minor alleles, controlled for the effect of comorbidities, remained significant only in females (OR [95% CI]: 0.035 [0.003; 0.408]). Our results strongly suggest that IFNL4 rs12979860 and rs368234815 polymorphisms independently predict the risk of COVID-19-related pneumonia development in females.
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COVID-19 , Humanos , Feminino , COVID-19/genética , SARS-CoV-2 , Alelos , Polimorfismo de Nucleotídeo Único , Bioensaio , Interferon lambda , Interleucinas/genéticaRESUMO
We describe the preparation, dynamic, assembly characteristics of vase-shaped basket 13- along with its ability to form an inclusion complex with anticancer drug mitoxantrone in abiotic and biotic systems. This novel cavitand has a deep nonpolar pocket consisting of three naphthalimide sides fused to a bicyclic platform at the bottom while carrying polar glycines at the top. The results of 1 H Nuclear Magnetic Resonance (NMR), 1 Hâ NMR Chemical Exchange Saturation Transfer (CEST), Calorimetry, Hybrid Replica Exchange Molecular Dynamics (REMD), and Microcrystal Electron Diffraction (MicroED) measurements are in line with 1 forming dimer [12 ]6- , to be in equilibrium with monomers 1(R) 3- (relaxed) and 1(S) 3- (squeezed). Through simultaneous line-shape analysis of 1 Hâ NMR data, kinetic and thermodynamic parameters characterizing these equilibria were quantified. Basket 1(R) 3- includes anticancer drug mitoxantrone (MTO2+ ) in its pocket to give stable binary complex [MTOâ1]- (Kd =2.1â µM) that can be precipitated inâ vitro with UV light or pH as stimuli. Both inâ vitro and inâ vivo studies showed that the basket is nontoxic, while at a higher proportion with respect to MTO it reduced its cytotoxicity inâ vitro. With well-characterized internal dynamics and dimerization, the ability to include mitoxantrone, and biocompatibility, the stage is set to develop sequestering agents from deep-cavity baskets.
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Antineoplásicos , Mitoxantrona , Mitoxantrona/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Espectroscopia de Ressonância MagnéticaRESUMO
Transforming growth factor beta (TGF-ß) is a ubiquitously distributed cytokine known to contribute to the pathogenesis of numerous pathological processes. The aim of this study was to measure serum concentrations of TGF-ß1 in severely ill COVID-19 patients and to analyze its relationship with selected hematological and biochemical parameters and with the disease outcome. The study population included 53 COVID-19 patients with severe clinical expression of the disease and 15 control subjects. TGF-ß1 was determined in serum samples and supernatants from PHA-stimulated whole blood cultures using ELISA assay. Biochemical and hematological parameters were analyzed using standard accepted methods. Our results showed that serum levels of TGF-ß1 in COVID-19 patients and controls correlate with the platelet counts. Also, positive correlations of TGF-ß1 with white blood cell and lymphocyte counts, platelet-to-lymphocyte (PLR) ratio, and fibrinogen level were shown, while negative correlations of this cytokine with platelet distribution width (PDW), D-dimer and activated partial thromboplastin time (a-PTT) values in COVID-19 patients were observed. The lower serum values of TGF-ß1 were associated with the unfavorable outcome of COVID-19. In conclusion, TGF-ß1 levels were strongly associated with platelet counts and unfavorable disease outcome of severely ill COVID-19 patients.
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The study's objective was to ascertain the results of sub-chronic therapy of various diuretics on the ischemia/reperfusion dysfunction of the heart in hypertensive rats by a global ischemia in an isolated rat heart model. The research included 40 spontaneously hypertensive male rats (Wistar Kyoto strain, body mass 250 ± 30 g, 8 weeks old) grouped into four groups. The animals were treated for 4 weeks with 10 mg/kg of hydrochlorothiazide, indapamide, or spironolactone per os. After a period of sub-chronic treatment, we analyzed hemodynamic measurements, echocardiography, and myocardial function according to the Langendorff retrograde perfusion method. The hearts were subjected to 20 min of global ischemia and then reperfused for 30 min (I20:R30). Cardiovascular parameters that depict the left ventricle functions were continuously monitored, while flowmetry was used to determine coronary flow values. Markers of oxidative stress were estimated from coronary venous effluent using spectrophotometry. All three examined diuretics (hydrochlorothiazide, spironolactone, indapamide) lowered the production of the majority of the detected prooxidants, reducing myocardial oxidative damage. The cardiological examination of heart function in vivo demonstrated that treatment with indapamide and spironolactone mitigates left ventricular hypertrophy but without significant lowering of blood pressure or increment in ejection fraction. Additionally, monitoring of cardiac function ex vivo indicated the cardiodepressant effect of spironolactone in spontaneously hypertensive rats.
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Indapamida , Traumatismo por Reperfusão Miocárdica , Ratos , Masculino , Animais , Ratos Endogâmicos SHR , Diuréticos/farmacologia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Espironolactona/farmacologia , Miocárdio , Hidroclorotiazida/farmacologia , Ratos Endogâmicos WKY , Isquemia , Reperfusão MiocárdicaRESUMO
OBJECTIVE: This study aimed to evaluate the dental pulp responses to recombinant human erythropoietin (rhEPO) and/or mineral trioxide aggregate (MTA) in pulp capping of inflamed dental pulp in vivo. MATERIALS AND METHODS: In accordance with ARRIVE guidelines, pulp inflammation was induced by exposing the maxillary first molars (n = 64) of Wistar rats (n = 32) to the oral environment for two days. The exposed pulps were randomly assigned four groups based on the pulp capping material: rhEPO, MTA, MTA + rhEPO, or an inert membrane. An additional eight rats formed the healthy control group. After four weeks, the animals were euthanized, and histological, qRT-PCR, and spectrophotometric techniques were employed to analyze the left maxillary segments, right first maxillary molars, and blood samples, respectively. Statistical significance was set at p < 0.05 and < 0.001. RESULTS: Pulp capping with rhEPO, MTA, or MTA + rhEPO resulted in lower inflammation and higher mineralization scores compared to untreated control. MTA + rhEPO group exhibited significantly decreased expression of tumor necrosis factor-alpha, and interleukin 1-beta, while MTA group showed substantially reduced expression of interferon-gamma. Both rhEPO and MTA + rhEPO groups presented elevated dentin matrix protein 1 levels compared to untreated control. Furthermore, pulp capping with rhEPO and/or MTA led to increased transforming growth factor-beta 1 expression and reductions of pro-inflammatory/immunoregulatory cytokine ratios and prooxidative markers. Pulp capping with rhEPO also resulted in increase of systemic antioxidative stress markers. CONCLUSION: Capping with rhEPO or MTA + rhEPO resulted in a favorable effect that was similar or even superior to that of MTA.
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This study evaluated the effect of sacubtril/valsartan on cardiac remodeling, molecular and cellular adaptations in experimental (rat) model of hypertension-induced hypertrophic cardiomyopathy. Thirty Wistar Kyoto rats, 10 healthy (control) and 20 rats with confirmed hypertension-induced hypertrophic cardiomyopathy (HpCM), were used for this study. The HpCM group was further subdivided into untreated and sacubitril/valsartan-treated groups. Myocardial structure and function were assessed using echocardiography, Langendorff's isolated heart experiment, blood sampling and qualitative polymerase chain reaction. Echocardiographic examinations revealed protective effects of sacubitril/valsartan by improving left ventricular internal diameter in systole and diastole and fractional shortening. Additionally, sacubitril/valsartan treatment decreased systolic and diastolic blood pressures in comparison with untreated hypertensive rats. Moreover, sacubitril/valsartan treatment reduced oxidative stress and apoptosis (reduced expression of Bax and Cas9 genes) compared to untreated rats. There was a regular histomorphology of cardiomyocytes, interstitium, and blood vessels in treated rats compared to untreated HpCM rats which expressed hypertrophic cardiomyocytes, with polymorphic nuclei, prominent nucleoli and moderately dilated interstitium. In experimental model of hypertension-induced hypertrophic cardiomyopathy, sacubitril/valsartan treatment led to improved cardiac structure, haemodynamic performance, and reduced oxidative stress and apoptosis. Sacubitril/valsartan thus presents as a potential therapeutic strategy resulted in hypertension-induced hypertrophic cardiomyopathy.
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Cardiomiopatia Hipertrófica , Hipertensão , Ratos , Animais , Tetrazóis/farmacologia , Tetrazóis/metabolismo , Tetrazóis/uso terapêutico , Valsartana/farmacologia , Valsartana/metabolismo , Valsartana/uso terapêutico , Miócitos Cardíacos/metabolismo , Cardiomiopatia Hipertrófica/tratamento farmacológico , Ratos Endogâmicos WKY , Modelos TeóricosRESUMO
OBJECTIVE: To quantify the incidence rate of anterior cruciate ligament (ACL) injuries and ankle sprains according to player sex, playing level, and exposure setting (training vs. games) in basketball players. METHODS: PubMed, MEDLINE, Google Scholar, and ScienceDirect were searched. Only studies reporting the number of ACL injuries and/or ankle sprains alongside the number of athlete-exposures (training sessions and/or games) in basketball players were included. RESULTS: Thirty studies (17 reporting ACL injuries and 16 reporting ankle sprains) were included in the meta-analysis. Higher (p < 0.05) ACL injury incidence rates per 1000 athlete-exposures were recorded in females (female: 0.20 95% confidence intervals [0.16-0.25]; male: 0.07 [0.05-0.08]; female-to-male ratio: 3.33 [3.10-3.57]), in players competing at higher playing levels (amateur: 0.06 [0.04-0.09]; intermediate: 0.16 [0.13-0.20]; elite: 0.25 [0.14-0.64]), and in games (games: female, 0.27 [0.21-0.32]; male, 0.06 [0.03-0.08]; training: female, 0.03 [0.02-0.05]; male: 0.01 [0.00-0.02]; game-to-training ratio: 7.90 [4.88-12.91]). Higher (p < 0.05) ankle sprain incidence rates per 1000 athlete-exposures were observed in males (female: 0.82 [0.61-1.03]; male: 0.90 [0.61-1.19]; female-to-male ratio: 0.91 [0.83-0.99]), in players competing at higher playing levels (amateur: 0.54 [0.51-0.57]; intermediate: 1.12 [1.00-1.24]; elite: 1.87 [1.29-2.46]), and in games (games: 2.51 [1.85-3.16]; training: 0.80 [0.52-0.80]; game-to-training ratio: 2.77 [2.35-3.26]). CONCLUSION: According to player sex, ACL injury incidence rate is higher in females, while ankle sprain incidence rate is greater in males. ACL injury and ankle sprain incidence rates are greater in players competing at higher playing levels and during games compared to training.
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Traumatismos do Tornozelo , Lesões do Ligamento Cruzado Anterior , Traumatismos em Atletas , Basquetebol , Entorses e Distensões , Humanos , Masculino , Feminino , Lesões do Ligamento Cruzado Anterior/epidemiologia , Incidência , Basquetebol/lesões , Traumatismos do Tornozelo/epidemiologia , Atletas , Traumatismos em Atletas/epidemiologia , Entorses e Distensões/epidemiologiaRESUMO
Mesenchymal stem cells (MSCs) are adult stem cells that reside in almost all postnatal tissues where, due to the potent regenerative, pro-angiogenic and immunomodulatory properties, regulate tissue homeostasis. Obstructive sleep apnea (OSA) induces oxidative stress, inflammation and ischemia which recruit MSCs from their niches in inflamed and injured tissues. Through the activity of MSC-sourced anti-inflammatory and pro-angiogenic factors, MSCs reduce hypoxia, suppress inflammation, prevent fibrosis and enhance regeneration of damaged cells in OSA-injured tissues. The results obtained in large number of animal studies demonstrated therapeutic efficacy of MSCs in the attenuation of OSA-induced tissue injury and inflammation. Herewith, in this review article, we emphasized molecular mechanisms which are involved in MSC-based neo-vascularization and immunoregulation and we summarized current knowledge about MSC-dependent modulation of OSA-related pathologies.
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Células-Tronco Adultas , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Apneia Obstrutiva do Sono , Animais , Inflamação/terapia , Anti-Inflamatórios/farmacologia , Imunomodulação , Apneia Obstrutiva do Sono/patologiaRESUMO
ABSTRACT: Milutinovic, A, Jakovljevic, V, Dabovic, M, Faude, O, Radovanovic, D, and Stojanovic, E. Isokinetic muscle strength in elite soccer players 3 months and 6 months after anterior cruciate ligament reconstruction. J Strength Cond Res 37(4): e297-e304, 2023-The aim of this study was to evaluate interlimb symmetry in quadriceps and hamstring peak torque of elite soccer players at 3 months (stage 1) and 6 months (stage 2) after anterior cruciate ligament (ACL) reconstruction. Eight male professional soccer players competing at the highest level across different European countries, who had undergone ACL reconstruction, participated in this study. All patients underwent a supervised physiotherapy program after surgery. Data analyses included the use of separate two-way repeated-measures analyses of variance and effect sizes. Although knee extensor and flexor strength of the non-injured limb was found to be relatively unaltered ( g = -0.10 to 0.00) between stage 1 and stage 2, comparisons across time points revealed moderate improvements in quadriceps peak torque ( p = 0.01, g = 0.52), hamstring peak torque ( p = 0.07, g = 0.51), and hamstring:quadriceps (H/Q) ratio ( p = 0.03, g = -0.68) of the injured leg, as well as small-large improvements in the quadriceps ( p = 0.004, g = 1.24) and hamstring limb symmetry index (LSI) ( p = 0.056, g = 0.41). A time-dependent moderate-large asymmetry observed at stage 1 between the injured and noninjured leg in quadriceps peak torque ( p < 0.001, g = -1.83), hamstring peak torque ( p = 0.157, g = -0.67), and the H:Q ratio ( p = 0.06, g = 1.01), as well as between the hamstring and quadriceps LSI ( p = 0.03, g = -0.74) was eliminated at stage 2 ( g = -0.31 to 0.42). Our findings indicate the importance of supervised and comprehensive therapy, as well as strength screening to assist in recovery aimed at optimizing identified strength deficits following ACL reconstruction.
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Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Futebol , Humanos , Masculino , Lesões do Ligamento Cruzado Anterior/cirurgia , Articulação do Joelho/fisiologia , Músculo Quadríceps/fisiologia , Força Muscular/fisiologia , TorqueRESUMO
Background and objectives: Taking into consideration the confirmed role of oxidative stress in ischemia/reperfusion injury and the insufficiency in knowledge regarding the phosphodiesterase 5 (PDE5)-mediated effects on the cardiovascular system, the aim of our study was to investigate the influence of two PDE5 inhibitors, tadalafil and vardenafil, with or without the addition of N(G)-nitro-L-arginine methyl ester (L-NAME), on oxidative stress markers, coronary flow and left ventricular function, both ex vivo and in vivo. Methods: This study included 74 male Wistar albino rats divided into two groups. In the first, 24 male Wistar rats were orally treated with tadalafil or vardenafil for four weeks in order to perform in vivo experiments. In the second, the hearts of 50 male Wistar albino were excised and perfused according to the Langendorff technique in order to perform ex vivo experiments. The hearts were perfused with tadalafil (10, 20, 50 and 200 nM), vardenafil (10, 20, 50 and 200 nM) and a combination of tadalafil/vardenafil and L-NAME (30 µM). The CF and oxidative stress markers, including nitrite bioaviability (NO2-), superoxide anion radical (O2-), and the index of lipid peroxidation, were measured in coronary effluent. Results: The L-arginin/NO system acts as the mediator in the tadalafil-induced effects on the cardiovascular system, while it seems that the vardenafil-induced increase in CF was not primarily induced by the NO system. Although tadalafil induced an increase in O2- in the two lowest doses, the general effects of both of the applied PDE5 inhibitors on oxidative stress were not significant. The ejection function was above 50% in both groups. Conclusions: Our results showed that both tadalafil and vardenafil improved the coronary perfusion of the myocardium and LV function by increasing the EF.
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Inibidores da Fosfodiesterase 5 , Função Ventricular Esquerda , Animais , Masculino , Ratos , Modelos Teóricos , NG-Nitroarginina Metil Éster/farmacologia , Estresse Oxidativo , Perfusão , Inibidores da Fosfodiesterase 5/farmacologia , Inibidores da Fosfodiesterase 5/uso terapêutico , Diester Fosfórico Hidrolases/metabolismo , Ratos Wistar , Volume Sistólico , Superóxidos/metabolismo , Tadalafila/farmacologia , Tadalafila/uso terapêutico , Dicloridrato de Vardenafila/farmacologia , Dicloridrato de Vardenafila/uso terapêuticoRESUMO
Background and Objectives: This study was conducted to examine the influence of different swimming and running protocols as forms of physiological preconditioning on an isolated rat heart's ischemia/reperfusion injury. Materials and Methods: This study was conducted on 60 male Wistar albino rats (6 weeks old, bw: 200 ± 20 g), divided into: CTRL group-a sedentary control group; sAeT-a group that underwent aerobic swimming conditioning using a swimming protocol for 8 weeks; sAnT-a group that underwent anaerobic swimming conditioning; rAeT-a group that underwent aerobic running conditioning; and rAnT-a group that underwent anaerobic running conditioning. After the preconditioning protocols, ex vivo estimating of myocardial function according to the Langendorff technique was performed. Results: The anaerobic running training decreased heart rate and the anaerobic swimming training reduced coronary flow, demonstrating the difference in the physiological heart response of aerobic/anaerobic physical training (p < 0.05). Heart rate was significantly reduced in both training swimming groups after a period of ischemia (p < 0.05). On the other hand, the anaerobic running protocol induced a significantly decreased heart rate in comparison with the aerobic running group and the sedentary group (p < 0.05). Conclusions: The data from this experimental study support many protective training effects, i.e., improved contractility, improved resting heart rate, and increased physical work capacity and exercise tolerance. Physical training in the form of anaerobic running induces greater heart preconditioning for reperfusion injury in comparison with anaerobic swimming training.
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Traumatismo por Reperfusão Miocárdica , Corrida , Ratos , Masculino , Animais , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Ratos Wistar , Natação/fisiologia , Isquemia , Modelos TeóricosRESUMO
Background and Objectives: Polycystic ovary syndrome (PCOS) is a frequent multifactorial endocrinopathy affecting women in the reproductive period, often associated with infertility and metabolic disorders. The use of animal models helps to better understand etiopathogenesis, enabling the examination of the effects of certain drugs in order to discover the best possible therapeutic approach. We tried to investigate the additional effect of estradiol-valerate (EV) and high-fat diet (HFD) in female rats to explore PCOS-related alterations with special focus on oxidative stress. Materials and Methods: Animals were divided into three groups: control group (CTRL, n = 6), estradiol-valerate group (EV, n = 6), and estradiol-valerate group on HFD (EV + HFD, n = 6). PCOS was induced by single subcutaneous injection of long-acting EV in a dose of 4 mg/per rat. We tried to improve the metabolic characteristics of the PCOS animal model by adding HFD, so the CTRL and EV group had a regular diet, while the EV + HFD group had HFD during the induction period of 60 days. Results: We observed alterations of anthropometric parameters and hormonal disturbances, along with estrus cycle impairment reassembly to obese-type PCOS phenotype. Moreover, glucose metabolism was impaired after addition of HFD to EV protocol, contrary to EV administered alone. Histological analysis confirmed more numerous cystic follicles after the combination of EV and HFD protocol. The alterations of oxidative stress markers could be related to and serve as the mechanistic base for development of PCOS-related endocrine, reproductive, and metabolic properties. Conclusions: The additive effect of EV and HFD was obvious in the majority of the parameters observed. Our study strongly demonstrated metabolic as well as reproductive properties of PCOS in rats.
Assuntos
Síndrome do Ovário Policístico , Ratos , Feminino , Animais , Humanos , Síndrome do Ovário Policístico/metabolismo , Dieta Hiperlipídica/efeitos adversos , Estradiol/efeitos adversos , Reprodução , Estresse Oxidativo , Valeratos/efeitos adversosRESUMO
This paper highlights the cardioprotective potential of sodium-glucose cotransporter 2 inhibitors (SLGT2i), as well as several most discussed mechanisms responsible for their cardioprotection. Cardiovascular diseases are considered a primary cause of death in nearly 80% of type 2 diabetes mellitus (T2DM) patients, with a 2-4-fold greater incidence of heart failure (HF) among diabetics. As novel hypoglycemics, SGLT2i showed exceptional cardiovascular benefits, reflected through robust reductions of cardiovascular mortality and hospitalization for HF in T2DM patients. Recently, those effects have been reported even in patients with HF and reduced ejection fraction irrespectively of diabetic status, suggesting that cardioprotective effects of SGLT2i are driven independently of their hypoglycemic actions. SGLT2i exerted hemodynamic and metabolic effects, partially driven by natriuresis and osmotic diuresis. However, those systemic effects are modest, and therefore cannot be completely related to the cardiac benefits of these agents in T2DM patients. Hence, increased circulating ketone levels during SGLT2i administration have brought out another hypothesis of a cardiac metabolic switch. Moreover, SGLT2i influence ion homeostasis and exert anti-inflammatory and antifibrotic effects. Their enviable influence on oxidative stress markers, as well as anti- and pro-apoptotic factors, have also been reported. However, since the main mechanistical contributor of their cardioprotection has not been elucidated yet, a joint action of systemic and molecular mechanisms has been suggested. In the light of ongoing trials evaluating the effects of SGLT2i in patients with HF and preserved ejection fraction, a new chapter of beneficial SGLT2i mechanisms is expected, which might resolve their main underlying action.
Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Volume SistólicoRESUMO
BACKGROUND: Type 2 diabetes mellitus (T2DM) is commonly associated with hyperglycemia, dyslipidemia, oxidative stress and inflammation which are well known cardiovascular risk factors. Pomegranate peel polyphenols have a proven hypolipemic, antioxidant and anti-inflammatory activity. However, there is a lack of clinical studies that would confirm its antioxidant and anti-inflammatory effects in diabetic patients. The potential of pomegranate peel extract (PoPEx) to counteract inflammation and oxidative stress in T2DM patients was investigated. For this purpose, a randomized, double-blind placebo-controlled study involving adult T2DM patients treated with PoPEx or placebo for eight-weeks was conducted. METHODS: Patients were randomly divided into two groups: the first group (n = 30) received capsules containing PoPEx 250 mg twice daily, while the placebo group (n = 30) received placebo capsules twice daily. Plasma concentration of inflammatory factors (interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) and high sensitivity C reactive protein (hsCRP)), oxidative stress biomarkers (thiobarbituric acid reactive substances (TBARS), nitrites (NO2-), superoxide anion radical (O2-), hydrogen peroxide (H2O2), total antioxidant capacity (TAC)), homocysteine and lipid profile were analyzed. RESULTS: The PoPEx treatment showed a significant reduction of inflammatory factors (IL-6, TNF-α, hsCRP), oxidative stress biomarkers (TBARS, NO2-, O2-) and homocysteine, while the TAC was increased. Moreover, a significant improvement in lipid profile was observed in the PoPEx group. Additional analysis showed a significant inverse correlation between the decrements of all measured inflammatory markers and TAC in the PoPEx group. CONCLUSIONS: The study demonstrated that eight-week-long PoPEx administration had favorable effects on inflammatory status and oxidative stress biomarkers in diabetic patients.