Pharmacology, Pharmacology, Toxicology and Pharmaceutics, Endocrine and Autonomic Systems, Reproductive Medicine
16
Scopus Publications
Scopus Publications
Ultrasound monitoring of the uterus and ovaries of dominant and subordinate females of yellow-breasted capuchin (Sapajus xanthosternos) and robust tufted capuchin (Sapajus robustus) in captive colonies during the ovarian cycle and anestrus periods Thalita A. Pissinatti, José A.S. Ribas, Elizabeth Maróstica, Alcides Pissinatti, Ana M.R. Ferreira Pesquisa Veterinaria Brasileira, 2019 The yellow-breasted capuchin (Sapajus xanthosternos) and robust tufted capuchin (Sapajus robustus) are endangered species due to destruction of their natural habitat and predatory chase. However, it is still necessary to elucidate some details of their reproductive physiology in order to obtain better indices in the assisted reproduction of these species. This study aimed to evaluate the ovarian cycle of 13 dominant and subordinate females of S. xanthosternos (n=8) and S. robustus (n=5) using sagittal and transversally scanned ultrasound of their uterus and ovaries. Sonograms were performed every seven days for two months. The ovarian cycle phase and anestrous condition were confirmed by colpocytology. Our results showed different uterine parameters (craniocaudal diameter, dorso-ventral diameter, and transverse diameter) (P<0.05) between anestrous subordinate females and other ovarian cycle phases and social classes. The mean of uterine volume was higher in dominant females than subordinate females in all cycle phases (P<0.05), except in follicular phase. During anestrus, endometrial width was smaller in subordinate females than in dominant females (P<0.05). Subordinate females showed differences in endometrial measures (P<0.05) between anestrous period and follicular and luteal periods. Ovarian measures in dominant females were higher than in subordinate females only during anestrus (P<0.05). In the subordinate females, ovarian parameters were different (P<0.05) between anestrus and follicular and luteal phases. Dominant females showed higher volume of right ovary compared to volume of the left ovary during anestrus and follicular phase (P<0.05). Follicles and corpus luteum were distinguished by ultrasonography in most exams (86.11%). During anestrus, measurable ovarian structures were not observed in both ovaries in dominant and subordinate females. In conclusion, the methodology used in this study allowed to evaluate the ovarian cycle in S. xanthosternos e S. robustus females and that cycle phase/anestrus and social class of the female influenced the size of the uterus and ovaries.
Effect of nebivolol on MIBG parameters and exercise in heart failure with normal ejection fraction Leandro Rocha Messias, Aryanne Guimarães Ferreira, Sandra Marina Ribeiro de Miranda, José Antônio Caldas Teixeira, Jader Cunha de Azevedo, Ana Carolina Nader Vasconcelos Messias, Elisabeth Maróstica, Claudio Tinoco Mesquita Arquivos Brasileiros De Cardiologia, 2016 BACKGROUND: More than 50% of the patients with heart failure have normal ejection fraction (HFNEF). Iodine-123 metaiodobenzylguanidine (123I-MIBG) scintigraphy and cardiopulmonary exercise test (CPET) are prognostic markers in HFNEF. Nebivolol is a beta-blocker with vasodilating properties. OBJECTIVES: To evaluate the impact of nebivolol therapy on CPET and123I-MIBG scintigraphic parameters in patients with HFNEF. METHODS: Twenty-five patients underwent 123I-MIBG scintigraphy to determine the washout rate and early and late heart-to-mediastinum ratios. During the CPET, we analyzed the systolic blood pressure (SBP) response, heart rate (HR) during effort and recovery (HRR), and oxygen uptake (VO2). After the initial evaluation, we divided our cohort into control and intervention groups. We then started nebivolol and repeated the tests after 3 months. RESULTS: After treatment, the intervention group showed improvement in rest SBP (149 mmHg [143.5-171 mmHg] versus 135 mmHg [125-151 mmHg, p = 0.016]), rest HR (78 bpm [65.5-84 bpm] versus 64.5 bpm [57.5-75.5 bpm, p = 0.028]), peak SBP (235 mmHg [216.5-249 mmHg] versus 198 mmHg [191-220.5 mmHg], p = 0.001), peak HR (124.5 bpm [115-142 bpm] versus 115 bpm [103.7-124 bpm], p= 0.043), HRR on the 1st minute (6.5 bpm [4.75-12.75 bpm] versus 14.5 bpm [6.7-22 bpm], p = 0.025) and HRR on the 2nd minute (15.5 bpm [13-21.75 bpm] versus 23.5 bpm [16-31.7 bpm], p = 0.005), but no change in peak VO2 and 123I-MIBG scintigraphic parameters. CONCLUSION: Despite a better control in SBP, HR during rest and exercise, and improvement in HRR, nebivolol failed to show a positive effect on peak VO2 and 123I-MIBG scintigraphic parameters. The lack of effect on adrenergic activity may be the cause of the lack of effect on functional capacity.
Do interleukin-1β levels correlate with MIBG and exercise parameters in heart failure? Leandro Rocha Messias, Maria Angela M. de Queiroz Carreira, Sandra Marina Marina Miranda, Jader Cunha de Azevedo, Paula Cardoso Benayon, Ronaldo Campos Rodrigues, Elisabeth Maróstica, Evandro Tinoco Mesquita, Claudio Tinoco Mesquita Arquivos Brasileiros De Cardiologia, 2013 BACKGROUND: Interleukin 1β (IL 1β) levels are associated with prognosis in heart failure. The cardiac adrenergic activity as assessed by metaiodobenzylguanidine (I123 MIBG) scintigraphy along with exercise parameters are important predictors of prognosis. The relationship between these variables is not fully established. OBJECTIVE: To evaluate the association of IL 1β levels with exercise and I123 MIBG parameters. METHODS: Cross-sectional observational study evaluating 25 consecutive patients with heart failure and ejection fraction lower than 45% by means of: determination of IL 1β levels; I123 MIBG parameters [early and late heart/mediastinum ratio, washout rate (WO)]; and treadmill exercise test using the ramp protocol. RESULTS: The patients were divided into two groups according to their IL 1β levels (normal vs. increased). The group with increased levels showed lower double-product reserve (DPR); lower functional capacity (FC); slower heart rate recovery at the first (HRR 1º) and second minute (HRR 2º); and higher WO. In the univariate analysis, all variables correlated with IL 1β; DPR: r = 0.203, p = 0.024; FC: r = 0.181, p = 0.034; HRR 1º: r = 0.182, p = 0.034; HRR 2º: r = 0.204, p = 0.023; WO: r = 0.263, p = 0.009. In the multivariate analysis, only WO maintained a significant correlation (r² = 0.263, p = 0.009). CONCLUSION: Adrenergic overactivity was the main determinant of IL 1β levels, thus demonstrating that an excessive sympathetic activity influences the systemic inflammatory response. Exercise test variables were not able to identify patients with high IL 1β levels.
Anti-atherogenic effects of a new thienylacylhydrazone derivative, LASSBio-788,in rats fed a hypercholesterolemic diet Nadia Alice Vieira da Motta, Arthur Eugen Kümmerle, Elisabeth Marostica, Caroline Fernandes dos Santos, Carlos Alberto Manssour Fraga, Eliezer Jesus Barreiro, Ana Luisa Palhares de Miranda, Fernanda Carla Ferreira de Brito Journal of Pharmacological Sciences, 2013 The compound LASSBio-788 (N-Allyl (2-thienylidene) 3,4-methylenedioxybenzoylhydrazine) is a thienylacylhydrazone derivative shown to have antiplatelet, vasodilatory, and anti-inflammatory properties in vitro. We hypothesize that LASSBio-788 may exert beneficial effects on atherosclerosis. Male wistar rats were divided into 4 groups: Control group received standard rat chow, hypercholesterolemic group (HC) and HC+788 (compound LASSBio-788 group) received hypercholesterolemic diet for 45 days. HC+788 group received compound LASSBio-788 (100 μmol/kg) once daily in the last 15 days. LASSBio-788 reduced the levels of total cholesterol (109.1 ± 4.3 vs. 361.0 ± 12.8 mg/dl), triglycerides (66.1 ± 1.1 vs. 186.9 ± 17.7 mg/dl), LDLc (63.2 ± 6.1 vs. 330.9 ± 9.7 mg/dl), VLDLc (9.8 ± 1.1 vs. 45.0 ± 4.6 mg/dl) and malondialdehyde (4.8 ± 0.3 vs. 9.4 ± 0.5 nmol/ml) compared to the HC group. LASSBio-788 presented antiplatelet properties and decreased inflammatory markers levels. LASSBio-788 promoted a decrease in contractile response to phenylephrine and an improvement in endothelium-dependent vasorelaxant response by increasing two-fold the expression of nitric oxide synthase (eNOS). Our results suggest that the compound LASSBio-788 represents a new multi-targeted drug candidate for the treatment of atherosclerosis.
Is abnormal adrenergic activation associated with abnormal heart rate recovery? Leandro Rocha Messias, Maria Angela M. de Queiroz Carreira, Sandra Marina Miranda, Jader Cunha de Azevedo, Isabela Ambrósio Gava, Ronaldo Campos Rodrigues, Elisabeth Maróstica, Claudio Tinoco Mesquita Arquivos Brasileiros De Cardiologia, 2012 BACKGROUND: Heart Rate Recovery (HRR) reflects the capacity of the cardiovascular system to reverse the vagal withdrawal caused by exercise. Scintigraphy with metaiodobenzylguanidine (I(123) MIBG) evaluates innervation and cardiac adrenergic activation. The association of these two methods is not well established. OBJECTIVE: To evaluate the association between HRR and washout rate (WO) of I(123) MIBG in patients with heart failure (HF). METHODS: Twenty-five patients with ejection fraction < 45% underwent exercise testing, and analysis of the variation of HRR from the 1st to the 8th minute after exertion. Submitted to I(123) MIBG, they were separated into groups by WO: G1) <27% and G2) ≥ 27%. For the statistical analysis Mann-Whitney's U test and Spearman's correlation coefficient were used. RESULTS: G2 showed a slower variation of HRR: 1st minute: G1: 21.5 (16.12 to 26.87) vs. G2: 11.00 (8.5 to 13.5) bpm, p = 0.001; 2nd minute: G1: 34 (29-39) vs. G2: 20 (14 - 26) bpm, p = 0.001; 3rd minute: G1: 46 (37.8 - 54.1) vs. G2: 30 (22 - 38) bpm, p = 0.005; 5th minute: G1: 51.5 (42 - 61) vs. G2: 39 (31.5 to 46.5) bpm, p = 0.013, and in the 8th minute: G1: 54.5 (46.5 - 62.5) vs. G2: 43 (34 - 52) bpm, p = 0.037. HRR in the 1st (r = -0.555, p = 0.004), and in the 2nd minute (r = -0.550, p = 0.004) were negatively correlated with WO. CONCLUSION: Patients with high HF and WO showed an abnormal HRR compared with patients with normal WO. These findings suggest that adrenergic activation may influence the HRR.
Relationship between cardiac adrenergic image and exercise testing in heart failure Leandro Rocha Messias, Maria Ângela M. de Queiroz Carreira, Sandra Marina Ribeiro de Miranda, Jader Cunha de Azevedo, Isabela Ambrósio Gava, Ronaldo Campos Rodrigues, Elizabeth Maróstica, Antônio Claudio Lucas da Nóbrega, Claudio Tinoco Mesquita Arquivos Brasileiros De Cardiologia, 2011 BACKGROUND: The exercise treadmill test can be used in ventricular dysfunction patients for functional capacity or predicting prognosis. The cardiac image with 123I MIBG shows cardiac sympathetic activation. OBJECTIVE: To evaluate the relationship between exercise treadmill test variables and cardiac image changes in 123I MIBG. METHODS: 23 patients with LVEF ≤ 45% performed scintigraphy cardiac with 123I MIBG and divided into two groups. G1: Washout rate < 27%; G2: ≥ 27%. Systolic blood pressure (SBP), heart rate (HR) and functional capacity were evaluated. It was performed Student t test or Mann-Whitney U test, Spearman coefficient and linear regression. RESULTS: SBP at exercise peak (G1: 181.00 ± 28.01; G2: 153.27 ± 27.71 mmHg, p = 0.027), SBP variation [G1: 64(47.5-80.5); G2: 36(25-47) mmHg, p = 0.015], the HR at exercise peak (G1: 136.91 ± 19.66; G2: 118.45 ± 13.98 bpm, p = 0.018) and chronotropic response (G1: 70.42 ± 17.94; G2: 49.47 ± 14.89%, p = 0.006), and functional capacity [G1: 8.37(6.47-10.27); G2: 4.42(2.46-6.38) METs, p = 0.003] were smaller in G2 group. There was negative correlation between Washout rate and SBP at exercise peak (r = -0.505, p = 0.014), variation in SBP (r = -0.493, p = 0.017) and functional capacity (r = -0.646, p = 0.001). Nevertheless, SBP at exercise peak (r = -0.422, p = 0.016) and functional capacity (r = -0.804, p = 0.004) were the only variables associated with Washout rate, after linear regression. CONCLUSION: In heart failure patients, the SBP at exercise peak and functional capacity were the variables associated with Washout rate.
Effects of the antiestrogen fulvestrant (ICI 182,780) on gene expression of the rat efferent ductules Fabiana Yasuhara, Gisele Renata Oliveira Gomes, Erica Rosanna Siu, Cláudia Igushi Suenaga, Elisabeth Maróstica, Catarina Segreti Porto, Maria Fatima Magalhaes Lazari Biology of Reproduction, 2008 The efferent ductules express the highest amount of estrogen receptors ESR1 (ERalpha) and ESR2 (ERbeta) within the male reproductive tract. Treatment of rats with the antiestrogen fulvestrant (ICI 182,780) causes inhibition of fluid reabsorption in the efferent ductules, leading to seminiferous tubule atrophy and infertility. To provide a more comprehensive knowledge about the molecular targets for estrogen in the rat efferent ductules, we investigated the effects of ICI 182,780 treatment on gene expression using a microarray approach. Treatment with ICI 182,780 increased or reduced at least 2-fold the expression of 263 and 98 genes, respectively. Not surprisingly, several genes that encode ion channels and macromolecule transporters were affected. Interestingly, treatment with ICI 182,780 markedly altered the expression of genes related to extracellular matrix organization. Matrix metalloproteinase 7 (Mmp7), osteopontin (Spp1), and neuronal pentraxin 1 (Nptx1) were among the most altered genes in this category. Upregulation of Mmp7 and Spp1 and downregulation of Nptx1 were validated by Northern blot. Increase in Mmp7 expression was further confirmed by immunohistochemistry and probably accounted for the decrease in collagen content observed in the efferent ductules of ICI 182,780-treated animals. Downregulation of Nptx1 probably contributed to the extracellular matrix changes and decreased amyloid deposition in the efferent ductules of ICI 182,780-treated animals. Identification of new molecular targets for estrogen action may help elucidate the regulatory role of this hormone in the male reproductive tract.
