DSpace Coleção: PMPGCF

Atividade imunomoduladora do esteroide cardiotônico BD-8 in vitro e in vivo

Fri, 26 Sep 2025 00:00:00 GMT

Título: Atividade imunomoduladora do esteroide cardiotônico BD-8 in vitro e in vivo Autor(es): Medeiros, Anna Beatriz Araujo Orientador: Mascarenhas, Sandra Rodrigues Abstract: Cardiotonic steroids (CTS) are compounds known to bind to the Na+/K+-ATPase and modulate various biological processes, including the immune response. γ-Benzylidene digoxin 8 (BD-8) is a synthetic CTS with immunomodulatory activity. Its action has been shown to reduce phagocytic activity, nitric oxide (NO) levels, and the pro-inflammatory cytokine IL-1β in murine peritoneal macrophages. Furthermore, BD-8 also reduced iNOS expression and the phosphorylation of NF-κB, ERK, and p38; however, further studies are needed to elucidate its action. Therefore, the objective of this study was to evaluate the immunomodulatory activity of BD-8 in murine peritoneal macrophages in vitro by analyzing Akt, mTOR, and Src proteins and in vivo in models of paw edema and acute lung injury (ALI). For in vitro tests, female Swiss albino mice were previously stimulated with an intraperitoneal (i.p.) injection of 4% thioglycolate. Macrophages from peritoneal lavage were cultured and stimulated with zymosan (0.2 mg/mL) and/or treated with BD-8 (10 μM) for 24 hours, for subsequent analysis of Akt, mTOR, and Src proteins by flow cytometry. For in vivo tests, in the paw edema model, the mice were treated with an i.p. injection of BD-8 (1.12 mg/kg; 0.56 mg/kg, and 0.28 mg/kg) and stimulated with an intraplantar injection of carrageenan (2.5%). Paw thickness was quantified using a digital caliper, and histological analysis of the paw was also performed. In the ALI model, the animals were stimulated with LPS via nasal instillation (5 mg/kg) and treated (i.p.) with BD-8 (0.56 mg/kg and 0.28 mg/kg) at 1, 24, and 48 hours after the LPS challenge. Bronchoalveolar lavage fluid (BALF) was collected and a blood smear was performed for analysis. As a result, it was seen that BD-8 negatively modulated Akt, mTOR, and Src proteins in vitro. Furthermore, this molecule also reduced paw edema at doses of 0.56 mg/kg and 0.28 mg/kg, showing a greater effect at the lowest dose tested; this result was also seen in the histological analysis. In the ALI model, BD-8, at the lowest dose tested, reduced cell migration, and at doses of 0.56 mg/kg and 0.28 mg/kg, it reduced neutrophils in bronchoalveolar lavage fluid (BALF). Additionally, the lowest dose tested also reduced total protein levels and the pro-inflammatory cytokine TNF-α in BALF. Histological analysis of lung tissue showed a reduction in ALI characteristics. Treatment with BD-8 did not modulate the number of blood leukocytes, indicating local action of the compound during the period tested. Therefore, this work contributes to the development of new substances with therapeutic potential, in addition to expanding the understanding of the BD-8 molecule and its ability to modulate biological and inflammatory processes. Editor: Universidade Federal da Paraíba Tipo: Dissertação

Efeitos do consumo de Konjac glucomanano (Konjac Massa mf®) sobre o perfil glicêmico e parâmetros metabólicos de camundongos com diabetes tipo 1 induzido por STZ

Thu, 29 Feb 2024 00:00:00 GMT

Título: Efeitos do consumo de Konjac glucomanano (Konjac Massa mf®) sobre o perfil glicêmico e parâmetros metabólicos de camundongos com diabetes tipo 1 induzido por STZ Autor(es): Andrade, Juliana Teles Orientador: Cruz, Josiane Campos Abstract: Type 1 diabetes mellitus (T1DM) is a metabolic condition characterized by immune- mediated destruction of pancreatic beta cells. Therapies aimed at enhancing insulin levels and sensitivity are essential for individuals with T1DM. Dietary interventions, particularly those involving dietary fibers, have emerged as promising non-pharmacological approaches for glycemic control. Konjac glucomannan (KGM) has shown notable hypoglycemic properties in animal models of T1DM. Thus, this study aimed to evaluate the effects of KGM, in the form of the commercial product Konjac Massa MF®, on the glycemic and lipid profiles of mice with STZ-induced T1DM. Male C57BL/6J mice rendered diabetic with streptozotocin (STZ) were treated with Konjac Massa MF® (120 mg/kg/day intragastric way) for four weeks. During the treatment period, glycemia, weight gain, water and food consumption were monitored. Glucose (IPGTT) and insulin (IPITT) tolerance tests were performed, followed by plasma collection for biochemical analyses. The results demonstrated a significant reduction in fasting glycemia in diabetic mice treated from the third week compared to untreated diabetics (245.20 ± 26.91 vs. 412.10 ± 25.18 mg/dL). However, no significant difference in glucose tolerance was observed between treated and untreated diabetic groups. The treated group exhibited improved insulin sensitivity (209.90 ± 57.20 vs. 378.50 ± 61.97 mg/dL; 60 min: 213.70 ± 48.49 vs. 361.00 ± 61.34 mg/dL; 90 min: 197.90 ± 51.85 vs. 316.30 ± 60.74 mg/dL; 120 min: 234.50 ± 59.23 vs. 318.30 ± 54.78 mg/dL). Treatment also resulted in reduced levels of serum MDA (17.10 ± 1.51 vs. 26.42 ± 1.48 nmol/dL), cholesterol (59.39 ± 8.61 vs. 156.83 ± 32.42 mg/dL), creatinine (1.46 ± 0.14 vs. 2.08 ± 0.23 nmol/dL), and ALT (39.39 ± 6.89 vs. 82.83 ± 25.19 nmol/dL). In conclusion, Konjac Massa MF® shows promise as a therapeutic agent for enhancing insulin sensitivity and hepatic function in T1DM models. Further research is warranted to elucidate the underlying protective mechanisms of KGM and to determine its clinical applicability in managing T1DM and its associated complications. Editor: Universidade Federal da Paraíba Tipo: Dissertação

Avaliação da variabilidade da frequência cardíaca e da pressão arterial em pacientes com teste positivo para COVID-19 em Unidade de Saúde da Família de João Pessoa - Paraíba

Fri, 04 Oct 2024 00:00:00 GMT

Título: Avaliação da variabilidade da frequência cardíaca e da pressão arterial em pacientes com teste positivo para COVID-19 em Unidade de Saúde da Família de João Pessoa - Paraíba Autor(es): Aguiar, Cecília Burle de Orientador: Balarini, Camille de Moura Abstract: The COVID-19 pandemic has significantly impacted public health, including cardiovascular autonomic dysfunctions. This study evaluated the effects of COVID-19 on autonomic regulation in patients approximately 113 days post-infection using heart rate variability (HRV) parameters and the Valsalva maneuver response. Fifty-eight participants were analyzed, comprising 29 previously infected individuals and 29 healthy controls recruited from the Verde Vida Family Health Unit in João Pessoa, Paraíba. Post-COVID-19 patients exhibited autonomic imbalance characterized by reduced vagal modulation, as evidenced by decreased RMSSD (control group: 41.63 ± 4.92; COVID-19 group: 29.98 ± 4.32; p = 0.048) and SD1 (control group: 29.47 ± 3.48; COVID-19 group: 21.22 ± 3.06; p = 0.048), positively correlated with the parasympathetic nervous system (PNS) index (control group: -0.64 (-1.40 – 0.49); COVID-19 group: -1.14 (-1.57 – (-0.64)); p = 0.029). Baroreflex sensitivity was also reduced, demonstrated by the lack of pressure reduction after the Valsalva maneuver in post-COVID-19 patients (mean arterial pressure, MAP, at rest: 94.98 ± 3.11 mmHg; post-MV: 93.31 ± 2.76 mmHg; p = 0.159), unlike the control group (MAP at rest: 93.32 ± 2.46 mmHg; post-MV: 88.47 ± 2.39 mmHg; p = 0.005). Infection severity correlated positively with age (r = 0.717; p < 0.001), resting systolic blood pressure (SBP; r = 0.458; p = 0.013), and stress index (r = 0.411; p = 0.027), suggesting sympathetic hyperactivity and greater cardiovascular burden in more severely affected individuals. This study underscores the association between COVID-19 and autonomic regulation alterations, irrespective of initial infection severity. Despite limitations such as small sample size and lack of pre-infection data, the findings enhance the understanding of the disease's long-term effects. HRV emerges as a non-invasive tool applicable to autonomic nervous system (ANS) monitoring, with potential to guide management strategies across all levels of post-COVID-19 healthcare. Editor: Universidade Federal da Paraíba Tipo: Tese

Avaliação da função vascular em modelo murino de aterosclerose tratado com lifepro, uma formulação nutracêutica composta por cepas de limosilactobacillus fermentum e polifenóis

Wed, 28 Aug 2024 00:00:00 GMT

Título: Avaliação da função vascular em modelo murino de aterosclerose tratado com lifepro, uma formulação nutracêutica composta por cepas de limosilactobacillus fermentum e polifenóis Autor(es): Cardoso, Emmily Ferreira de Farias Orientador: Balarini, Camille de Moura Abstract: Atherosclerosis is one of the leading cardiovascular diseases. Hypercholesterolemia has been identified as the main atherogenic factor in humans, exacerbated by an unbalanced diet. Probiotics in combination with phenolic compounds have proven effective in reducing lipidemia in animals. The Federal University of Paraíba developed a new nutraceutical formulation by combining the probiotic Limosilactobacillus fermentum (strains 139, 263, 296) and the phenolic compounds quercetin and resveratrol (LifePro). This research aimed to investigate the vascular effects of the nutraceutical in apolipoprotein E knockout atherosclerotic mice (apoE-/- ) subjected to an atherogenic diet. Three groups were analyzed: control animals without genetic modification (wild type, WT); apoE-/- animals that received a vehicle, and apoE-/- animals that received the nutraceutical for eight weeks. At the end, the animals were euthanized to assess biochemical and inflammatory patterns, lipid deposition, and vascular reactivity in the aorta artery. The administration of the nutraceutical had a hypocholesterolemic effect, reducing cholesterol in treated apoE-/- animals (579±46 mg/dL##) compared to vehicle-treated apoE-/- animals (978±68 mg/dL**), but not in relation to the healthy control group (73±6 mg/dL). There was also a hypoglycemic effect in the treated group (249±16 mg/dL#) compared to the saline apoE-/- group (300±12 mg/dL). Triglycerides were also reduced in treated animals (145±18 mg/dL#* vs. apoE-/- saline 211±16 mg/dL**). The lipoprotein profile showed alterations in the apoE-/- vehicle group (HDL: 17±2 mg/dL** vs. WT 41±2 mg/dL and LDL: 159±21** mg/dL vs. WT: 5±0.7 mg/dL), while HDL and LDL levels were not altered by the treatment. On the other hand, VLDL was reduced in the treated group (503±62 mg/dL#*) compared to the saline group (776±46 mg/dL##), both differing from healthy animals (28±3 mg/dL). The treatment did not influence food intake or weight. Oxidative stress was higher in the apoE-/- saline group (30±1 mmol/mL vs. WT 13±1 mmol/mL), and LifePro reduced MDA concentrations (14±2### mmol/mL). Regarding vascular reactivity, the apoE-/- vehicle group showed increased vasoconstriction in response to phenylephrine (Rmax: 88±7%) compared to the healthy control group (Rmax: 70±3%) and impaired endothelium-dependent relaxation (apoE-/- vehicle Rmax: 48±6% vs. WT Rmax: 89±5%), highlighting endothelial dysfunction in this group. The nutraceutical improved endothelial dysfunction by reducing vasoconstrictive behavior (apoE-/- treated Rmax: 50±3%##) and increasing relaxation in response to acetylcholine (apoE-/- treated Rmax: 107±12%##). The treatment restored NO-mediated relaxation and reduced the impact of oxidative stress in organ baths. Concerning the inflammatory profile, TNF (18±1 pg/mL vs. 7±1 pg/mL) and MCP-1 (145±12** pg/mL vs. 77±8 pg/mL) cytokines were higher in the apoE-/- saline group compared to WT, while IL-6 and IL-10 levels did not show alterations between groups. The treatment did not modify cytokine levels. Lipid deposition in the aortic arch was accentuated in apoE-/- saline animals (45±2%), while treatment (27±2%##) reduced plaque percentage by 1.2 times. Thus, we suggest that the treatment proved effective in a murine model of atherosclerosis. Editor: Universidade Federal da Paraíba Tipo: Dissertação