36 results on '"Nascimento CP"'
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2. Unmasking hidden risks: The surprising link between PDE5 inhibitors and seizure susceptibility.
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Silva ALMD, Nascimento CP, Azevedo JEC, Vieira LR, Hamoy AO, Tiago ACDS, Martins Rodrigues JC, de Araujo DB, Favacho Lopes DC, de Mello VJ, and Hamoy M
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- Animals, Male, Rats, Anticonvulsants adverse effects, Diazepam, Pentylenetetrazole adverse effects, Phenobarbital adverse effects, Rats, Wistar, Sildenafil Citrate adverse effects, Tadalafil adverse effects, Phosphodiesterase 5 Inhibitors adverse effects, Seizures
- Abstract
Background: Phosphodiesterase 5 inhibitors (PDE5i) are the first line treatment for erectile dysfunction; however, several articles and case reports have shown central nervous system effects, that can cause seizures in susceptible patients. This study aims to describe the changes caused by the use of Sildenafil and Tadalafil through the analysis of abnormalities expressed in the electrocorticogram (ECoG) of rats and evaluate the seizure threshold response and treatment of seizures with anticonvulsants., Materials and Methods: The study used 108 rats (Wistar). Before surgery for electrode placement in dura mater, the animals were randomly separated into 3 experiments for electrocorticogram analysis. Experiment 1: ECoG response to using PD5i (Sildenafil 20mg/kg and Tadalafil 2.6mg/kg p.o.). Experiment 2: ECoG response to the use of PD5i in association with Pentylenetetrazole (PTZ-30 mg/kg i.p.), a convulsive model. Experiment 3: ECoG response to anticonvulsant treatment (Phenytoin, Phenobarbital and Diazepam) of seizures induced by association IPDE5 + PTZ. All recordings were made thirty minutes after administration of the medication and analyzed for ten minutes, only once. We considered statistical significance level of *p<0.05, **p<0.01 and ***p < 0.001., Results: After administration of Sildenafil and Tadalafil, there were increases in the power of recordings in the frequency bands in oscillations in alpha (p = 0.0920) and beta (p = 0.602) when compared to the control group (p<0.001). After the use of Sildenafil and Tadalafil associated with PTZ, greater potency was observed in the recordings during seizures (p<0.001), however, the Sildenafil group showed greater potency when compared to Tadalafil (p<0.05). Phenobarbital and Diazepam showed a better response in controlling discharges triggered by the association between proconvulsant drugs., Conclusions: PDE5i altered the ECoG recordings in the rats' motor cortexes, demonstrating cerebral asynchrony and potentiating the action of PTZ. These findings demonstrate that PDE5i can lower the seizure threshold., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Silva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2023
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3. The elusive Luminal B breast cancer and the mysterious chemokines.
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de Araújo RA, da Luz FAC, da Costa Marinho E, Nascimento CP, Mendes TR, Mosca ERT, de Andrade Marques L, Delfino PFR, Antonioli RM, da Silva ACAL, Dos Reis Monteiro MLG, Neto MB, and Silva MJB
- Abstract
Purpose: Invasive ductal breast cancer (IDC) is heterogeneous. Staging and immunohistochemistry (IH) allow for effective therapy but are not yet ideal. Women with Luminal B tumors show an erratic response to treatment. This prospective study with 81 women with breast cancer aims to improve the prognostic stratification of Luminal B patients., Methods: This is a prospective translational study with 81 women with infiltrating ductal carcinoma, grouped by TNM staging and immunohistochemistry, for survival analysis, and their correlations with the chemokines. Serum measurements of 13 chemokines were performed, including 7 CC chemokines [CCL2(MCP1), CCL3(MIP1α), CCL4(MIP1β), CCL5(Rantes), CCL11(Eotaxin), CCL17(TARC), CCL20(MIP3α)], 6 CXC chemokines [CXCL1(GroAlpha), CXCL5(ENA78), CCXCL8(IL-8), CXCL9(MIG), CXCL10(IP10), CXCL11(ITAC)]., Results: Overall survival was significantly dependent on tumor staging and subtypes by immunohistochemistry, with a median follow-up time the 32.87 months (3.67-65.63 months). There were age correlations with IP10/CXCL10 chemokines (r = 0.4360; p = 0.0079) and TARC/CCL17 (Spearman + 0.2648; p = 0.0360). An inverse correlation was found between body weight and the chemokines Rantes/CCL5 (r = - 0.3098; p = 0.0169) and Eotaxin/CCL11 (r = - 0.2575; p = 0.0470). Smokers had a higher concentration of MIP3α/CCL20 (Spearman + 0.3344; p = 0.0267). Luminal B subtype patients who expressed lower concentrations of ENA78/CXCL5 (≤ 254.83 pg/ml) (Log-Rank p = 0.016) and higher expression of MIP1β/CCL4 (> 34.84 pg/ml) (Log-Rank p = 0.014) had a higher risk of metastases., Conclusion: Patients with Luminal B breast tumors can be better stratified by serum chemokine expression, suggesting that prognosis is dependent on biomarkers other than TNM and IH., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2023
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4. Analysis of the surgical approach in prostate cancer staging: results from the surveillance, epidemiology and end results program.
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da Luz FAC, Nascimento CP, da Costa Marinho E, Felicidade PJ, Antonioli RM, de Araújo RA, and Silva MJB
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- Male, Humans, Neoplasm Staging, Retrospective Studies, Prognosis, Lymphatic Metastasis pathology, Lymph Nodes surgery, Lymph Nodes pathology, Prostatic Neoplasms epidemiology, Prostatic Neoplasms surgery, Prostatic Neoplasms pathology
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Surgery is not used as a criterion for staging prostate cancer, although there is evidence that the number of analyzed and affected lymph nodes have prognosis value. The aim of this study was to determine whether there are significant differences in staging criteria in patients who underwent prostatectomy compared to those who did not, and whether the number of affected and analyzed lymph nodes (LN) plays a prognostic role. In this retrospective study, a test cohort consisting of 404,210 newly diagnosed men with prostate cancer, between 2004 and 2010, was obtained from the 17 registries (Nov 2021 submission); a validation consisting of 147,719 newly diagnosed men with prostate cancer between 2004 and 2019 was obtained from the 8 registries (Nov 2021 submission). Prostate cancer-specific survival was analyzed by Kaplan-Meier curves, survival tables and Cox regression; overall survival was analyzed only to compare Harrell's C-index between different staging criteria. In initial analyses, it was observed that the prognostic value of lymph node metastasis changes according to the type of staging (clinical or pathological), which is linked to the surgical approach (prostatectomy). Compared with T4/N0/M0 patients, which are also classified as stage IVA, N1/M0 patients had a shorter [adjusted HR: 1.767 (1429-2184), p < 0.0005] and a longer [adjusted HR: 0.832 (0.740-0.935), p = 0.002] specific survival when submitted to prostatectomy or not, respectively. Analyzing separately the patients who were submitted to prostatectomy and those who were not, it was possible to obtain new LN metastasis classifications (N1: 1 + LN; N2: 2 + LNs; N3: > 2 + LNs). This new (pathological) classification of N allowed the reclassification of patients based on T and Gleason grade groups, mainly those with T3 and T4 disease. In the validation group, this new staging criterion was proven to be superior [specific survival C-index: 0.908 (0.906-0.911); overall survival C-index: 0.788 (0.786-0.791)] compared to that currently used by the AJCC [8th edition; specific survival C-index: 0.892 (0.889-0.895); overall survival C-index: 0.744 (0.741-0.747)]. In addition, an adequate number of dissected lymph nodes results in a 39% reduction in death risk [adjusted HR: 0.610 (0.498-0.747), p < 0.0005]. As main conclusion, the surgery has a major impact on prostate cancer staging, mainly modifying the effect of N on survival, and enabling the stratification of pathological N according to the number of affected LN. Such a factor, when considered as staging criteria, improves the prognosis classification., (© 2023. The Author(s).)
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- 2023
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5. Survival differences between women and men in the non-reproductive cancers: Results from a matched analysis of the surveillance, epidemiology, and end-results program.
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da Luz FAC, Nascimento CP, Marinho EDC, Felicidade PJ, Antonioli RM, de Araújo RA, and Silva MJB
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- Humans, Male, Female, Aged, Retrospective Studies, Kaplan-Meier Estimate, Neoplasms epidemiology
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Background: Men with non-reproductive cancers have a discrepant outcome compared to women. However, they differ significantly in the incidence of cancer type and characteristics., Methods: Patients with single primary cancer who were 18 years or older and whose data were gathered and made accessible by the Surveillance, Epidemiology, and End Results (SEER) program were included in this retrospective analysis. Kaplan-Meier curves and Cox regression before and after propensity score matching were performed to analyze the risk survival by sex., Results: Among the 1,274,118 patients included [median (range) age, 65 year (18-85+) years; 688,481 (54.9%) male]. The median follow-up was 21 months (0-191). Substantial improvements in survival were observed for both sexes during the years of inclusion analyzed, with no difference between them, reaching a reduction of almost 17% of deaths in 2010, and of almost 28% in 2015, compared to 2004. The women had a median survival of 74 months and overall mortality of 48.7%. Males had a median survival of 30 months (29.67-30.33) with an overall mortality of 56.2%. The PSM showed a reduced difference (6 months shorter median survival and 2.3% more death in men), but no change in hazards was observed compared to the unmatched analysis [adjusted HR: 0.888 (0.864-0.912) vs. 0.876 (0.866-0.886) in unmatched]., Conclusions: The discrepancy in survival between men and women is not explained only by the incidence of more aggressive and more advanced cancers in the former., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Luz, Nascimento, Marinho, Felicidade, Antonioli, Araújo and Silva.)
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- 2023
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6. Caffeine intoxication: Behavioral and electrocorticographic patterns in Wistar rats.
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Azevedo JEC, da Silva ALM, Vieira LR, Nascimento CP, Pereira RG, Rodrigues SF, Hamoy AO, Mello VJ, Araújo DB, Barbas LAL, Lopez MEC, Lopes DCF, and Hamoy M
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- Rats, Animals, Rats, Wistar, Caffeine toxicity, Anticonvulsants toxicity, Seizures chemically induced, Diazepam adverse effects, Phenobarbital, Pentylenetetrazole toxicity, Phenytoin pharmacology
- Abstract
Caffeine is a psychoactive substance used worldwide. The present study analyzes the seizure-related behavior and electrocorticographic (ECoG) patterns observed in rats following of a toxic dose of caffeine (150 mg/kg; intraperitoneal). Sixty-three rats were divided into three experiments: 1-Behavior's Description associated with caffeine-induced convulsion; 2- Comparison of the electrocorticographic patterns induced by caffeine and pentylenetetrazole, and 3- Assessment of the electrocorticographic response to antiepileptic drugs (diazepam, phenytoin, and phenobarbital). The behavioral analysis demonstrated tonic-clonic seizures with a loss of postural reflex and a latency of 365.8 s after the caffeine's administration. Caffeine-induced changes in the ECoG were consistent with the development of seizures with rapid evolution and burst potential consistent with the behavioral patterns observed during the caffeine-induced seizure. The ECoG of the brainwaves varied significantly between the seizures caused by caffeine and pentylenetetrazole. The predominant brain forces observed during the seizures were beta-band oscillations. The caffeine-induced seizures were resistant to attempted control with phenytoin and phenobarbital, but responded well to diazepam, which is consistent with a study of Pilocarpine, which showed that diazepam has anticonvulsant effects. These findings are important for the development of effective treatments for caffeine intoxication, in particular for individuals with a low seizure threshold., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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- 2022
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7. The effect of delayed treatment in breast cancer patients: How much is too late? An experience of a single-center study effect of surgery delay in survival.
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Luz FACD, Marinho EDC, Nascimento CP, Marques LA, Delfino PFR, Antonioli RM, Araújo RA, and Silva MJB
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- Female, Humans, Chemotherapy, Adjuvant, Kaplan-Meier Estimate, Neoadjuvant Therapy, Prognosis, Retrospective Studies, Time-to-Treatment, Breast Neoplasms drug therapy
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Background and Objectives: Proper treatment is critical for control and curative intent in breast cancer. Delays in receiving treatment can influence patients' prognoses., Methods: Retrospective, observational, single-center study based on data from medical records of 747 patients with non-metastatic invasive ductal breast carcinoma (I-III) in the initial analysis, comprising 554 patients undergoing adjuvant and 193 neoadjuvant treatment. Kaplan-Meier, Cox regression and time-dependent Cox regression were performed to obtain the predictive value of time to surgery and time to first treatment. Immortal time bias was managed and only 721 patients were included in the multivariable analysis., Results: During a median observation of 64.4 months, there were 140 death events and 177 disease progression events. Time to surgery (TTS) and time from completion of neoadjuvant chemotherapy to surgery (TNS) showed a significant impact on overall survival, associated with a 6% increased chance of death [HR: 1.06 (1.03-1.09), p < 0.001] and 4% [HR: 1.04 (1.00-1.09), p = 0.048] with a one-month increment, respectively. By multivariable analysis, continuous TTS had a different weight as a prognostic factor in stage IIIA/IIIB [adjusted HR: 1.249 (1.072-1.454), p = 0.004] compared to stage I/II [adjusted HR: 1.093 (1.048-1.141), p < 0.0005]. Likewise, TNS was significant after adjusting for other factors [adjusted HR: 1.092 (1.038-1.148), p = 0.001]., Conclusion: Delay in receiving surgery with curative intent impairs the survival of patients with breast cancer., Competing Interests: Declarations of interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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- 2022
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8. Epidermal growth factor receptor (EGFR) expression in the serum of patients with triple-negative breast carcinoma: prognostic value of this biomarker.
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de Araújo RA, da Luz FAC, da Costa Marinho E, Nascimento CP, de Andrade Marques L, Delfino PFR, Antonioli RM, Araújo BJ, da Silva ACAL, Dos Reis Monteiro MLG, Neto MB, and Silva MJB
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Background: Epidermal growth factor receptor (EGFR) overexpression has been considered a poor prognostic factor in breast cancer., Methodology: A prospective study of 206 women with breast cancer analysed by stages (I, II, III and IV) and by immunohistochemical subtype (Luminal A, Luminal B, HER2+ and triple-negative (TN)); 89 healthy controls with normal recent mammography were included. The EGFR measured in the serum (sEGFR) was detected by the Enzyme-Linked Immunosorbent Assay (ELISA) method (R&D Systems kit DY231) collected by blood before any treatment in patients. Kaplan-Meier method and Cox regression were carried out to obtain the prognostic value, considering significance if p < 0.05., Results: With a median follow-up of 36.6 months, 47 deaths occurred. Multivariable Cox regression showed difference of overall survival (OS) associated with sEGFR levels (sEGFR ≤ or > 47.8 ng/mL) in patients with TN cancers, but not of Luminal A, Luminal B or HER2+ subtypes; adjusted by stage, the death risk increased by approximately 415% [hazard ratio (HR): 5.149 (1.900-13.955), p = 0.001] for patients with sEGFR > 47.8 ng/mL compared to patients with a lower sEGFR value. There was no significant correlation of sEGFR with staging, histological tumour grade (G1/G2/G3), Ki67 (< or ≥14%) or body mass index., Conclusions: Increased sEGFR expression in patients with TN tumours is a significant predictor of lower OS and its quantification is inexpensive and straightforward., Competing Interests: The authors declare that there are no conflicts of interest., (© the authors; licensee ecancermedicalscience.)
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- 2022
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9. PTH Spikes During Surgical Treatment for Secondary and Tertiary Hyperparathyroidism: A Prospective Observational Study.
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Silveira AA, Brescia MDG, do Nascimento CP, Magnabosco FF, Arap SS, and de Menezes Montenegro FL
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- Humans, Monitoring, Intraoperative methods, Parathyroid Glands surgery, Parathyroid Hormone, Hyperparathyroidism, Secondary etiology, Hyperparathyroidism, Secondary surgery, Parathyroidectomy methods
- Abstract
Background: The aim of the present study was to determine whether PTH spikes in renal hyperparathyroidism can interfere with the interpretation of intraoperative PTH monitoring and to determine its frequency and characteristics., Methods: This was a prospective observational study of consecutive patients who underwent surgical treatment in a single tertiary institution. Patients were divided into two groups: spike and no spike. Patients with secondary and tertiary hyperparathyroidism were analyzed separately. Intraoperative PTH monitoring by venous serial samples: two samples were taken before the excision of the parathyroid gland, and two others were taken after resection., Results: PTH spikes occurred in 23.5% (53 of 226), and their occurrence was similar between secondary and tertiary hyperparathyroidism patients (p = 0.074). The relative PTH spike intensity was higher in transplanted patients than in dialysis patients (55 vs. 20%, p = 0.029). A characteristic of the secondary hyperparathyroidism patients was the highest frequency of surgical failure (23 vs. 7.5%, p = 0.016) and the higher occurrence of supernumerary glands in the spike group (23 vs. 10.3%, p = 0.035). Supernumerary parathyroid was associated with surgical failure [19.1 (6.5-55.7) odds ratio [confidence interval], p < 0.001). In the studies evaluating the diagnostic test validity for patients on dialysis and experiencing spikes, the most significant impacts were in the sensitivity, accuracy, and negative predictive value of the method., Conclusions: PTH spikes occurred in up to 23.5% of renal hyperparathyroidism surgical treatments and can negatively influence the intraoperative parathyroid hormone monitoring. Regarding the phenomenon of PTH spikes, it is prudent to think about the possibility of a hyperplastic supernumerary gland., (© 2022. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)
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- 2022
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10. A Combination of Curcuma longa and Diazepam Attenuates Seizures and Subsequent Hippocampal Neurodegeneration.
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Nascimento CP, Ferreira LO, da Silva ALM, da Silva ABN, Rodrigues JCM, Teixeira LL, Azevedo JEC, de Araujo DB, Hamoy AO, Gonçalves BH, Coelho BHO, Lopes DCF, and Hamoy M
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Epilepsy is one of the most common neurological disorders, which occurs due to the instability in the inhibitory and excitatory synaptic transmissions in the brain. However, many patients develop resistance to the available drugs, which results in cell degeneration caused due to inadequate control of the seizures. Curcumin, Curcuma longa , is known to be effective for the treatment of organic disorders and may prevent seizures, reduce oxidative stress, and decrease brain damage. Given this, the present study evaluated the antiepileptic effects of C. longa in comparison with both the diazepam and the combined application of these two substances, in terms of their effects on the brain activity and the potential histopathological changes in the hippocampus. This study used male Wistar rats (age: 10-12 weeks; weight: 260 ± 20 g), which were pretreated for 4 days with either saline, C. longa , diazepam, or C. longa + diazepam; and on the fifth day, pentylenetetrazol (PTZ) was administered to induce the seizure. In the C. longa group, a significant increase was observed in the latency of the onset of seizure-related behavior. Surprisingly, however, the combined treatment resulted in the best control of the seizure-related behavior, with the greatest latency of the onset of spasms and isolated clonic seizures. This group also obtained the best results in the electroencephalographic trace and seizure control, with a reduction in the frequency and amplitude of the spike-waves. In the saline group, PTZ significantly reduced the number of cells present in the CA1 and CA3 regions of the hippocampus, while the combined treatment obtained the best results in terms of the preservation of the neuron-like cells. These findings indicate that C. longa may contribute to the control of both seizures and the cell damage induced by PTZ, and that its association with diazepam may be a potentially effective option for the treatment of epilepsy in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nascimento, Ferreira, Silva, Silva, Rodrigues, Teixeira, Azevedo, Araujo, Hamoy, Gonçalves, Coelho, Lopes and Hamoy.)
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- 2022
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11. A hierarchical approach to combine histological grade and immunohistochemical factors to identify high-risk luminal breast cancers.
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da Luz FAC, da Costa Marinho E, Nascimento CP, de Andrade Marques L, Delfino PFR, Antonioli RM, de Araújo RA, and Silva MJB
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Background: The luminal subtype accounts for ~70% of newly diagnosed breast cancer patients. Although it has a better prognosis, approximately 30% of them develop a late relapse. Identifying those patients is of interest to improve treatment decisions., Methods: A retrospective observational, single-centre study based on data from medical records of 572 non-metastatic (I-III) invasive ductal breast carcinoma patients, 448 with luminal tumours and 124 with triple-negative tumours. Kaplan-Meier, Cox regression and time-dependent Cox regression were carried out to obtain the prognosis value of risk factors., Results: During a median observation of 5.5 years, 105 distant metastasis events and 105 all-cause deaths were observed. In addition to known clinicopathological factors (i.e., age, tumour size and lymph node metastasis), the high semi-quantitative expression of both hormone receptors was associated with distant metastasis-free survival (DMFS) (adjusted hazard ratio (HaR): 0.524 (0.316-0.867), p = 0.012) and overall survival (OS) (adjusted HaR: 0.486 (0.286-0.827), p = 0.008). The stratified analysis made it possible to identify risk modification factors. Subsequent stratification by histological grade, Ki-67 and semi-quantitative PR expression or, mainly, the composite semi-quantitative expression of hormone receptors (cHR) enabled the identification of luminal breast cancer patients of adjuvant schema at higher risk for metastasis and death. However, initial analyses including patients of neoadjuvant therapy pointed to a path of subsequent stratification by cHR and histological grade, also enabling grouping of luminal breast cancer patients with similar prognosis for DMFS (cHR ≤ 4+ G2 or G3 versus triple-negative, adjusted HaR: 0.703 (0.415-1.189), p = 0.189) and OS (cHR ≤4+ G2 or G3 versus triple-negative, adjusted HaR: 0.662 (0.403-1.088), p = 0.104)., Conclusion: The semi-quantitative expression of both cHR, Ki-67 proliferation index and histological grade can identify luminal breast cancer patients at greater risk of developing metastasis and death when combined in a hierarchical fashion, and could be useful for a better prognosis stratification in services from low- and middle-income countries., Competing Interests: The authors declared no conflicts of interest., (© the authors; licensee ecancermedicalscience.)
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- 2022
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12. The effectiveness of radiotherapy in preventing disease recurrence after breast cancer surgery.
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Luz FACD, Marinho EDC, Nascimento CP, Marques LA, Duarte MBO, Delfino PFR, Antonioli RM, Araújo RA, and Silva MJB
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- Female, Humans, Margins of Excision, Neoplasm Recurrence, Local pathology, Neoplasm Staging, Radiotherapy, Adjuvant, Retrospective Studies, Breast Neoplasms radiotherapy, Breast Neoplasms surgery
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Background and Objectives: The locoregional management of breast cancer has a critical impact on prognosis. This study aimed to analyze the effectiveness of radiotherapy against the deleterious effect of positive surgical margins on disease outcomes., Methods: Retrospective, single-center study enrolled 721 breast cancer patients with a median follow-up of approximately 64.50 months (3.67-247.40). Analyses were performed considering the end of adjuvant therapy, except endocrine therapy. Kaplan-Meier and Cox regression were performed to obtain the predictive value of treatments., Results: The minimally adequate radiotherapy (≥45 cGy) was associated with improved outcomes in breast cancer patients compared to inadequate radiotherapy (<45 cGy/no) by controlling locoregional relapses and distant metastasis. In patients with positive surgical margins (n = 53), radiotherapy was associated with an approximate decrease of 90% in locoregional relapse risk [adjusted HR: 0.108 (0.012-0.932), p = 0.043]. Radiotherapy did not alter the adverse effect of positive surgical margins, especially in patients with a higher risk of poorly differentiated tumors (n = 146), presence of lymphovascular invasion (n = 163), and triple-negative subtype (n = 113). Notwithstanding, radiotherapy was associated with respective decreases of distant metastasis risk of 75.2% [adjusted HR: 0.248 (0.081-0.762), p = 0.015] and 67.8% [adjusted HR: 0.322 (0.101-1.029), p = 0.056] in patients with triple-negative tumors or with lymphovascular invasion., Conclusion: Adequate radiotherapy is associated with better outcomes in breast cancer. Despite improving locoregional relapse-free survival, radiotherapy does not ablate positive surgical margins, a factor of poorer prognosis that prevails mainly in patients with factors of higher relapse risk., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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- 2022
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13. 100 YEARS OF VITAMIN D: Supraphysiological doses of vitamin D changes brainwave activity patterns in rats.
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Lima GO, Menezes da Silva AL, Azevedo JEC, Nascimento CP, Vieira LR, Hamoy AO, Oliveira Ferreira L, Bahia VRLO, Muto NA, Lopes DCF, and Hamoy M
- Abstract
Low plasma levels of vitamin D causes bone mineral change that can precipitate osteopenia and osteoporosis and could aggravate autoimmune diseases, hypertension and diabetes. The demand for vitamin D supplementation becomes necessary; however, the consumption of vitamin D is not without risks, which its toxicity could have potentially serious consequences related to hypervitaminosis D, such as hypercalcemia and cerebral alterations. Thus, the present study describes the electroencephalographic changes caused by supraphysiological doses of vitamin D in the brain electrical dynamics and the electrocardiographic changes. After 4 days of treatment with vitamin D at a dose of 25,000 IU/kg, the serum calcium levels found were increased in comparison with the control group. The electrocorticogram analysis found a reduction in wave activity in the delta, theta, alpha and beta frequency bands. For ECG was observed changes with shortened QT follow-up, which could be related to serum calcium concentration. This study presented important evidence about the cerebral and cardiac alterations caused by high doses of vitamin D, indicating valuable parameters in the screening and decision-making process for diagnosing patients with symptoms suggestive of intoxication.
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- 2022
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14. Prognosis value of lymphovascular invasion in patients with invasive ductal breast carcinoma according to lymph node metastasis status.
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da Luz FAC, da Costa Marinho E, Nascimento CP, de Andrade Marques L, Delfino PFR, Antonioli RM, de Araújo RA, and Silva MJB
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Background: Tumour lymphovascular invasion is not routinely assessed in all pathology services, and whether reporting it quantitatively or qualitatively is the main factor associated with the loss of this prognostic event. This study aimed to analyse the prognostic value of qualitatively reported lymphovascular invasion in patients with invasive breast ductal carcinoma., Methods: This was a retrospective, single-center study, enrolling a total of 426 patients with invasive ductal carcinoma of the breast with a report of lymphovascular invasion, with a median follow-up of approximately 4.5 years. Kaplan-Meier and Cox regression was performed to obtain the predictive value of lymphovascular invasion. Propensity score matching was performed to reduce bias by standardising factors with significant differential distribution of lymphovascular invasion status., Results: Lymphovascular invasion was present in 197 (49.2%) patients. Multivariate Cox regression showed that lymphovascular invasion independently increases the risk of death by almost two times (adjusted hazard ratio (HR): 2.045 (1.226-3.406), p = 0.006) and the risk of distant metastasis by more than two times (adjusted HR: 2.373 (1.404-4.010), p = 0.001). Subgroup analysis after matching by propensity score in adjuvant-only patients showed that the lymphovascular invasion is a factor of increased death in N- patients (adjusted HR: 12.597 (1.624-97.728), p = 0.015) and of distant metastasis-free survival in N+ patients (adjusted HR: 4.862 (1.649-14.335), p = 0.004) and almost for N- patients (adjusted HR 7.905 (0.969-64.509), p = 0.004)., Conclusion: The presence of lymphovascular invasion is a predictor of worse prognosis in patients with invasive ductal carcinoma of the breast, even with metastatic lymph node disease (N1-N3)., Competing Interests: The authors declared no conflict of interests., (© the authors; licensee ecancermedicalscience.)
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- 2022
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15. The benefits of trastuzumab in the treatment of HER2+ breast cancer as a function of exposure time.
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da Luz FAC, da Costa Marinho E, Nascimento CP, de Andrade Marques L, Delfino PFR, Antonioli RM, Silva MJB, and de Araújo RA
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Background: Breast cancer is a heterogeneous disease with overexpression of several receptors, such as human epidermal receptor 2 (HER2), which is a prognostic and predictive biomarker for treatment with the anti-HER2 monoclonal antibody trastuzumab. This study aimed to test the contribution of this regimen in patients with overexpression/amplification of HER2 for periods shorter than the 1-year treatment recommendation., Methods: A retrospective single-centre study involving 155 patients with non-metastatic (stages I-III) invasive ductal HER2+ breast carcinoma, with a median follow-up of 48.9 months after completion of adjuvant therapy, except endocrine therapy., Results: About 60% of patients received trastuzumab therapy for a median time of 365 days. Although the use of trastuzumab for a short period has provided some benefit, analyses of survival with a continuous dependent variable have revealed a minimum time for improved survival. In the multivariate analysis by Cox regression, trastuzumab use duration exceeding 9 weeks resulted in protection against distant metastasis (adjusted HR: 0.307 (0.139-0.678), p = 0.004), disease progression (adjusted hazard ratio (HR) 0.353 (0.175-0.714), p = 0.004) and death (adjusted HR: 0.267 (0.105-0.678), p = 0.005), being superior to multimodal systemic therapy with chemotherapy and to endocrine therapy without trastuzumab, but inferior to almost 1 year of administration of this monoclonal antibody, especially regarding overall survival (adjusted HR: 0.203 (0.069-0.596), p = 0.004)., Conclusion: Despite showing some benefits, the protective effect derived from a suboptimal time of trastuzumab exposure is inferior to the standard course of 1 year., Competing Interests: The authors declared that there are no conflicts of interest., (© the authors; licensee ecancermedicalscience.)
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- 2022
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16. Operable breast cancer: How not to worsen the prognosis, especially in triple negative and stage II tumors.
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de Araújo RA, Cordero da Luz FA, da Costa Marinho E, Mendes TR, Nascimento CP, Ribeiro Delfino PF, Antonioli RM, Ruas AC, Alves AR, Araújo BJ, de Paula Machado JP, Guedes Pereira TO, França do Espírito Santo M, and Barbosa Silva MJ
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- Adult, Aged, Aged, 80 and over, Female, Follow-Up Studies, Humans, Middle Aged, Neoplasm Recurrence, Local pathology, Neoplasm Staging, Retrospective Studies, Survival Rate, Triple Negative Breast Neoplasms pathology, Margins of Excision, Mastectomy mortality, Neoplasm Recurrence, Local surgery, Triple Negative Breast Neoplasms surgery
- Abstract
Introduction: Oncological surgery must follow some fundamental principles to be truly curative, one of which is the resection of the tumor with surgical margins free of neoplasia. In breast cancer, surgery with positive margins should be expanded immediately. There are probably different intensities, between the stages and molecular subtypes of operable breast cancer, of worsening prognosis due to the surgical margin compromised by the neoplasia in women not submitted to the necessary enlargement of the positive surgical margin. MATERIALS AND., Methods: Seven hundred and forty-seven women with invasive ductal carcinoma of the breast, analyzing anatomical-pathological information, types of surgery, molecular subtypes, and the presence or absence of the surgical margin compromised by neoplasia., Results: Sixty-one (8.2%) patients had positive surgical margin, causing 2.85 times more risk of locoregional relapse compared to negative surgical margin by multivariate analysis. In subgroup analysis, among stages I, II and III, stage II was the most negatively impacted, with those patients presenting 2.42 times more risk of distant metastasis and 4.94 times more risk of locoregional relapses compared to negative surgical margin by multivariate analysis. Among the molecular subtypes, Triple Negative tumors with a positive surgical margin had 3.56 times more risk of death, 4.98 times more risk of distant metastasis and 5.55 times more risk of locoregional relapse compared to negative surgical margin by multivariate analysis., Conclusions: The positive surgical margin, especially in Stage II and Triple-Negative breast cancer patients negatively impact the patient's evolution, increasing risk of distant metastasis and death., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
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17. Molecular dynamics simulations and analysis for bioinformatics undergraduate students.
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Justino GC, Nascimento CP, and Justino MC
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- Humans, Universities, Computational Biology education, Molecular Dynamics Simulation, Natural Cytotoxicity Triggering Receptor 3 chemistry, Software, Students psychology
- Abstract
A computational biochemistry laboratory, fitted for bioinformatics students, is presented. The molecular dynamics package GROMACS is used to prepare and simulate a solvated protein. Students analyze the trajectory with different available tools (GROMACS and VMD) to probe the structural stability of the protein during the simulation. Students are also required to make use of Python libraries and write their own code to probe non-covalent interactions between the amino acid side chains. Based on these results, students characterize the system in a qualitatively approach but also assess the importance of each specific interaction through time. This work mobilizes biochemical concepts and programming skills, fostering critical thinking and group work and developing presenting skills., (© 2021 International Union of Biochemistry and Molecular Biology.)
- Published
- 2021
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18. Invasive mechanical ventilation and biomarkers as predictors of bronchopulmonary dysplasia in preterm infants.
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Nascimento CP, Maia LP, Alves PT, Paula AT, Cunha Junior JP, Abdallah VOS, Ferreira DMLM, Goulart LR, and Azevedo VMGO
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- Biomarkers, Humans, Infant, Infant, Newborn, Infant, Premature, Prospective Studies, Respiration, Artificial, Bronchopulmonary Dysplasia diagnosis
- Abstract
Objectives: To evaluate the impact of invasive mechanical ventilation associated with two serum inflammatory cytokines and clinical indicators, on the second day of life, as predictors of bronchopulmonary dysplasia in very low birth weight preterm infants. It was hypothesized that the use of invasive mechanical ventilation in the first hours of life is associated with biomarkers that may predict the chances of preterm infants to develop bronchopulmonary dysplasia., Methods: Prospective cohort of 40 preterm infants with gestational age <34 weeks and birth weight <1500 g. The following were analyzed: clinical variables; types of ventilator support used (there is a higher occurrence of bronchopulmonary dysplasia when oxygen supplementation is performed by long periods of invasive mechanical ventilation); hospitalization time; quantification of two cytokines (granulocyte and macrophage colony stimulating factor [GM-CSF] and eotaxin) in blood between 36 and 48 h of life. The preterm infants were divided in two groups: with and without bronchopulmonary dysplasia., Results: The GM-CSF levels presented a significantly higher value in the bronchopulmonary dysplasia group (p = 0.002), while eotaxin presented higher levels in the group without bronchopulmonary dysplasia (p = 0.02). The use of continuous invasive mechanical ventilation was associated with increased ratios between GM-CSF and eotaxin (100% sensitivity and 80% specificity; receiver operating characteristic area = 0.9013, CI = 0.7791-1.024, p < 0.0001)., Conclusions: The duration of invasive mechanical ventilation performed in the first 48 h of life in the very low birth weight infants is a significant clinical predictor of bronchopulmonary dysplasia. The use of continuous invasive mechanical ventilation was associated with increased ratios between GM-CSF and eotaxin, suggesting increased lung injury and consequent progression of the disease., (Copyright © 2020 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)
- Published
- 2021
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19. Acute and long-term kidney function after parathyroidectomy for primary hyperparathyroidism.
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Belli M, Martin RM, Brescia MDG, Nascimento CP Jr, Massoni Neto LM, Arap SS, Ferraz-de-Souza B, Moyses RMA, Peacock M, and Montenegro FLM
- Subjects
- Acute Kidney Injury etiology, Adolescent, Adult, Aged, Aged, 80 and over, Creatinine blood, Female, Glomerular Filtration Rate, Humans, Male, Middle Aged, Parathyroid Hormone blood, Vitamin D analogs & derivatives, Vitamin D blood, Acute Kidney Injury epidemiology, Hyperparathyroidism, Primary surgery, Parathyroidectomy adverse effects, Postoperative Complications epidemiology
- Abstract
Background: In kidney transplant patients, parathyroidectomy is associated with an acute decrease in renal function. Acute and chronic effects of parathyroidectomy on renal function have not been extensively studied in primary hyperparathyroidism (PHPT)., Methods: This retrospective cohort study included 494 patients undergoing parathyroidectomy for PHPT. Acute renal changes were evaluated daily until day 4 post-parathyroidectomy and were stratified according to acute kidney injury (AKI) criteria. Biochemical assessment included serum creatinine, total and ionized calcium, parathyroid hormone (PTH), and 25-hydroxyvitamin D (25OHD). The estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI equation. We compared preoperative and postoperative renal function up to 5 years of follow-up., Results: A total of 391 (79.1%) patients were female, and 422 (85.4%) were non-African American. The median age was 58 years old. The median (first and third quartiles) preoperative serum creatinine, PTH and total calcium levels were 0.81 mg/dL (0.68-1.01), 154.5 pg/mL (106-238.5), and 10.9 mg/dL (10.3-11.5), respectively. The median (first and third quartiles) preoperative eGFR was 86 mL/min/1.73 m2 (65-101.3). After surgery, the median acute decrease in the eGFR was 21 mL/min/1.73 m2 (p<0.0001). Acutely, 41.1% of patients developed stage 1 AKI, 5.9% developed stage 2 AKI, and 1.8% developed stage 3 AKI. The acute eGFR decrease (%) was correlated with age and PTH, calcium and preoperative creatinine levels in univariate analysis. Multivariate analysis showed that the acute change was related to age and preoperative values of ionized calcium, phosphorus and creatinine. The change at 12 months was related to sex, preoperative creatinine and 25OHD. Permanent reduction in the eGFR occurred in 60.7% of patients after an acute episode., Conclusion: There was significant acute impairment in renal function after parathyroidectomy for PHPT, and almost half of the patients met the criteria for AKI. Significant eGFR recovery was observed during the first month after surgery, but a small permanent reduction may occur. Patients treated for PHPT seemed to present with prominent renal dysfunction compared to patients who underwent thyroidectomy., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2020
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20. Critical analysis of the intraoperative parathyroid hormone decrease during parathyroidectomy for secondary and tertiary hyperparathyroidism.
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Silveira AA, Brescia MDG, do Nascimento CP Jr, Arap SS, and Montenegro FLM
- Subjects
- Adult, Clinical Decision-Making methods, Feasibility Studies, Female, Follow-Up Studies, Humans, Hyperparathyroidism, Secondary blood, Hyperparathyroidism, Secondary diagnosis, Hyperparathyroidism, Secondary etiology, Male, Middle Aged, Parathyroid Glands transplantation, Prospective Studies, Renal Insufficiency, Chronic blood, Sensitivity and Specificity, Transplantation, Autologous, Treatment Outcome, Hyperparathyroidism, Secondary surgery, Monitoring, Intraoperative methods, Parathyroid Hormone blood, Parathyroidectomy, Renal Insufficiency, Chronic complications
- Abstract
Background: This study aims to determine whether intraoperative parathyroid hormone monitoring helps to predict early surgical outcomes in patients with renal hyperparathyroidism and evaluate the impact on decision making during surgery., Methods: A prospective study was conducted. Serial samples of the intraoperative parathyroid hormone were collected; 2 of these were taken before the excision, and 2 were taken after the planned parathyroid resection (10 minutes and 15 minutes). We tested the criterion of an intraoperative parathyroid hormone percentage decay ≥80% of the highest value of the basal samples as a predictor of success., Results: Of the 228 patients, parathyroidectomy achieved success in 92.1%. In patients with secondary hyperparathyroidism, the failure group showed a tendency to stabilize or even increase the intraoperative parathyroid hormone values from the 10-minute measure (577 pg/mL) to the 15-minute measure (535 pg/mL) (P = .903). Conversely, intraoperative parathyroid hormone continued to drop in those with a successful outcome: 245 pg/mL (10 minutes) and 206 pg/mL (15 minutes) (P < .001). The failure group had a significantly lower percentage decay (P < .001) from baseline when compared with the success group. The intraoperative parathyroid hormone influenced the surgical management in up to 7% of the cases. The intraoperative parathyroid hormone dosage method showed an accuracy of 86%, a sensitivity of 88%, and specificity of 67%., Conclusion: In patients with renal hyperparathyroidism undergoing parathyroidectomy, the use of intraoperative parathyroid hormone may help to predict an early therapeutic outcome with high sensitivity and accuracy by indicating the operation's success when there is an 80% reduction of baseline intraoperative parathyroid hormone 15 minutes after removal of the enlarged glands, an associated continuous decrease in serum intraoperative parathyroid hormone levels between 10 and 15 minutes, and achievement of plasma target values <500 pg/mL., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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21. Trophic morphology features allow Astyanax endemic species coexistence in a Neotropical river system.
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do Nascimento CP, Dos Santos NCL, Dal Vesco BM, and Gomes LC
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- Animals, Brazil, Gills anatomy & histology, Nutritional Status, Species Specificity, Tropical Climate, Characidae anatomy & histology, Food Chain, Rivers
- Abstract
Resource partitioning has an essential role in interspecific relations, especially in congener species, which share many morphological traits. In some places, small characids coexist through resource partitioning, which may reduce their interspecific competition. Astyanax species (e.g., Astyanax minor, Astyanax gymnodontus and Astyanax bifasciatus), for example, coexist in different water bodies from the Iguaçu River basin. These species have high phenotypic plasticity and many morphologic specializations that allow them to live in different habitats. Based on evidences that these species modified their feeding habits because of changes in resource availability in Iguaçu River, this study tested two hypotheses: (a) there are differences in head morphology, number of teeth and number of gill rakers among the species of Astyanax; and (b) there are differences in gill arch and gill raker morphology among the species of Astyanax, which may favour their trophic resource partitioning in Iguaçu River. The head morphological traits and quantitative morphological characters were summarized in a principal coordinates analysis (PCoA), and the analysis of similarities (ANOSIM) showed significant differences among species. Gill morphological measurements were analysed through analysis of covariance (ANCOVA), and it also showed significant differences in gill arch and gill raker morphology among species. Therefore, the analysis of ecomorphological traits related to trophic habits revealed some differences that may suggest a tendency of reducing competition for trophic resources in the Iguaçu River basin., (© 2020 The Fisheries Society of the British Isles.)
- Published
- 2020
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22. Ganoderma lucidum Ameliorates Neurobehavioral Changes and Oxidative Stress Induced by Ethanol Binge Drinking.
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Nascimento CP, Luz DA, da Silva CCS, Malcher CMR, Fernandes LMP, Dalla Santa HS, Gomes ARQ, Monteiro MC, Ribeiro CHMA, Fontes-Júnior EA, and Maia CSF
- Subjects
- Animals, Female, Male, Rats, Rats, Wistar, Binge Drinking complications, Ethanol adverse effects, Nervous System Diseases drug therapy, Oxidative Stress drug effects, Reishi chemistry
- Abstract
Ganoderma lucidum , mushroom used for centuries by Asian peoples as food supplement, has been shown interesting biological activities, including over the Central Nervous System. Besides, these mushroom bioactive compounds present antioxidant and anti-inflammatory activities. On the side, binge drinking paradigm consists of ethanol exposure that reflects the usual consumption of adolescents, which elicits deleterious effects, determined by high ethanol consumption, in a short period. In this study, we investigated whether the Aqueous Extract of G. lucidum (AEGl) reduces the behavioral disorders induced by alcohol. Male ( n = 30) and female Wistar rats ( n = 40), seventy-two days old, were used for behavioral/biochemical and oral toxicity test, respectively. Animals were exposed to 5 binges (beginning at 35 days old) of ethanol (3 g/kg/day) or distilled water. Twenty-four hours after the last binge administration, animals received AEGl (100 mg/kg/day) or distilled water for three consecutive days. After treatment protocol, open field, elevated plus maze, forced swim, and step-down inhibitory avoidance tests were performed. Oxidative stress parameters were measured to evaluate the REDOX balance. Our results demonstrated that AEGl elicited the recovery of spontaneous horizontal exploration capacity, anxiogenic- and depressive-profile, as well as short-term memory damage induced by binge-ethanol exposure. The behavioral effects of the extract were associated to the reequilibrium of the animals' REDOX balance. Thus, AEGl, a medicinal mushroom, ameliorates behavioral alteration on a model of motor, cognitive and psychiatric-like disorders induced by binge drinking paradigm and emerges as a useful tool as a food supplement in the management of disorders of alcoholic origin., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Chirlene Pinheiro Nascimento et al.)
- Published
- 2020
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23. Biochemical and functional characterization of a mitochondrial citrate carrier in Arabidopsis thaliana.
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Brito DS, Agrimi G, Charton L, Brilhaus D, Bitetto MG, Lana-Costa J, Messina E, Nascimento CP, Feitosa-Araújo E, Pires MV, Pérez-Díaz JL, Obata T, Porcelli V, Palmieri L, Araújo WL, Weber APM, Linka N, Fernie AR, Palmieri F, and Nunes-Nesi A
- Subjects
- Biological Transport, Dicarboxylic Acid Transporters genetics, Dicarboxylic Acid Transporters metabolism, Fatty Acids metabolism, Fumarates metabolism, Gene Expression, Genes, Fungal, Genes, Plant, Kinetics, Liposomes, Mitochondria metabolism, Mitochondrial Proteins metabolism, Nitrogen metabolism, Saccharomyces cerevisiae genetics, Seedlings growth & development, Succinates metabolism, Tricarboxylic Acids metabolism, Arabidopsis genetics, Arabidopsis growth & development, Arabidopsis metabolism, Carrier Proteins genetics, Carrier Proteins metabolism
- Abstract
A homolog of the mitochondrial succinate/fumarate carrier from yeast (Sfc1p) has been found in the Arabidopsis genome, named AtSFC1. The AtSFC1 gene was expressed in Escherichia coli, and the gene product was purified and reconstituted in liposomes. Its transport properties and kinetic parameters demonstrated that AtSFC1 transports citrate, isocitrate and aconitate and, to a lesser extent, succinate and fumarate. This carrier catalyzes a fast counter-exchange transport as well as a low uniport of substrates, exhibits a higher transport affinity for tricarboxylates than dicarboxylates, and is inhibited by pyridoxal 5'-phosphate and other inhibitors of mitochondrial carriers to various degrees. Gene expression analysis indicated that the AtSFC1 transcript is mainly present in heterotrophic tissues, and fusion with a green-fluorescent protein localized AtSFC1 to the mitochondria. Furthermore, 35S-AtSFC1 antisense lines were generated and characterized at metabolic and physiological levels in different organs and at various developmental stages. Lower expression of AtSFC1 reduced seed germination and impaired radicle growth, a phenotype that was related to reduced respiration rate. These findings demonstrate that AtSFC1 might be involved in storage oil mobilization at the early stages of seedling growth and in nitrogen assimilation in root tissue by catalyzing citrate/isocitrate or citrate/succinate exchanges., (© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)
- Published
- 2020
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24. Corrigendum to "Quality of life after surgery in secondary hyperparathyroidism comparing subtotal parathyroidectomy to total parathyroidectomy with immediate parathyroid autograft - a prospective randomized trial" [Surgery 164 (2018) 978-985].
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Filho WA, van der Plas WY, Brescia MDG, Nascimento CP Jr, Goldenstein PT, Neto LMM, Arap SS, Custodio MR, Bueno RO, Moyses RMA, Jorgetti V, Kruijff S, and Montenegro FLM
- Published
- 2019
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25. Quality of life after surgery in secondary hyperparathyroidism, comparing subtotal parathyroidectomy with total parathyroidectomy with immediate parathyroid autograft: Prospective randomized trial.
- Author
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Filho WA, van der Plas WY, Brescia MDG, Nascimento CP Jr, Goldenstein PT, Neto LMM, Arap SS, Custodio MR, Bueno RO, Moyses RMA, Jorgetti V, Kruijf S, and Montenegro FLM
- Subjects
- Adult, Age Factors, Female, Follow-Up Studies, Humans, Hyperparathyroidism, Secondary blood, Hyperparathyroidism, Secondary etiology, Kidney Failure, Chronic blood, Kidney Failure, Chronic complications, Kidney Failure, Chronic therapy, Male, Middle Aged, Parathyroid Hormone blood, Parathyroidectomy adverse effects, Preoperative Period, Prospective Studies, Renal Dialysis adverse effects, Surveys and Questionnaires statistics & numerical data, Transplantation, Autologous adverse effects, Transplantation, Autologous methods, Treatment Outcome, Hyperparathyroidism, Secondary surgery, Parathyroid Glands transplantation, Parathyroidectomy methods, Quality of Life
- Abstract
Background: No prospective randomized data exist about the impact of various strategies of parathyroidectomy in secondary hyperparathyroidism patients on quality of life and its possible relationship with metabolic status after the operation., Method: In a prospective randomized trial, the Short Form 36 Health Survey Questionnaire was applied to 69 patients undergoing parathyroidectomy through various approaches: subtotal parathyroidectomy (n = 23), total parathyroidectomy (PTx) with autotransplantation of 45 fragments (n = 25) and PTx with autotransplantation of 90 fragments (n = 21). The questionnaire was completed at three moments: (1) preoperatively, (2) 6 months after surgery, and (3) 12 months after surgery., Results: Quality of life improved significantly in the physical component summary score in all three groups. Subtotal parathyroidectomy scores changed from 30.6 preoperatively to 51.7 6 months after surgery and 53.7 12 months after surgery. Total arathyroidectomy with autotransplantation of 45 fragments scores changed from 33.8 preoperatively to 52.6 6 months after surgery and 55.2 12 months after surgery. Total parathyroidectomy with autotransplantation of 90 fragments scores changed from 31.8 preoperatively to 50.5 6 months after surgery and 55.2 12 months after surgery (all groups P < .0001). No significant difference was detected in the physical component summary score change among the three groups. The physical component summary score was negatively correlated to age, parathormone, and alkaline phosphatase preoperatively., Conclusion: Parathyroidectomy significantly improves quality of life in hemodialysis patients with secondary hyperparathyroidism, regardless of the type of operation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Published
- 2018
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26. Microglia/Astrocytes-Glioblastoma Crosstalk: Crucial Molecular Mechanisms and Microenvironmental Factors.
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Matias D, Balça-Silva J, da Graça GC, Wanjiru CM, Macharia LW, Nascimento CP, Roque NR, Coelho-Aguiar JM, Pereira CM, Dos Santos MF, Pessoa LS, Lima FRS, Schanaider A, Ferrer VP, and Moura-Neto V
- Abstract
In recent years, the functions of glial cells, namely, astrocytes and microglia, have gained prominence in several diseases of the central nervous system, especially in glioblastoma (GB), the most malignant primary brain tumor that leads to poor clinical outcomes. Studies showed that microglial cells or astrocytes play a critical role in promoting GB growth. Based on the recent findings, the complex network of the interaction between microglial/astrocytes cells and GB may constitute a potential therapeutic target to overcome tumor malignancy. In the present review, we summarize the most important mechanisms and functions of the molecular factors involved in the microglia or astrocytes-GB interactions, which is particularly the alterations that occur in the cell's extracellular matrix and the cytoskeleton. We overview the cytokines, chemokines, neurotrophic, morphogenic, metabolic factors, and non-coding RNAs actions crucial to these interactions. We have also discussed the most recent studies regarding the mechanisms of transportation and communication between microglial/astrocytes - GB cells, namely through the ABC transporters or by extracellular vesicles. Lastly, we highlight the therapeutic challenges and improvements regarding the crosstalk between these glial cells and GB.
- Published
- 2018
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27. Parathyroidectomy in patients with chronic kidney disease: Impacts of different techniques on the biochemical and clinical evolution of secondary hyperparathyroidism.
- Author
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Albuquerque RFC, Carbonara CEM, Martin RCT, Dos Reis LM, do Nascimento CP Júnior, Arap SS, Moysés RMA, Jorgetti V, Montenegro FLM, and de Oliveira RB
- Subjects
- Adult, Calcium blood, Female, Fibroblast Growth Factor-23, Glucuronidase metabolism, Humans, Hyperparathyroidism, Secondary blood, Kidney Failure, Chronic complications, Kidney Failure, Chronic therapy, Klotho Proteins, Male, Middle Aged, Parathyroid Hormone blood, Proliferating Cell Nuclear Antigen metabolism, Receptor, Fibroblast Growth Factor, Type 1 metabolism, Receptors, Calcitriol metabolism, Receptors, Calcium-Sensing metabolism, Retrospective Studies, Transcription Factor Pit-1 metabolism, Transplantation, Autologous, Hyperparathyroidism, Secondary surgery, Parathyroid Glands metabolism, Parathyroid Glands transplantation, Parathyroidectomy methods
- Abstract
Background: Parathyroidectomy (PTx) decreases the mortality rate of refractory secondary hyperparathyroidism (rSHP) due to chronic kidney disease. A consensus regarding which techniques of PTx are associated with better outcomes is not available. The aims of this study are to evaluate the clinical and laboratory evolution of 49 hemodialysis patients with rSHP who underwent PTx using different techniques., Methods: Patients underwent subtotal PTx (sub-PTx) or total PTx with autotransplantation (AT) of 45 (PTx-AT
45 ) or 90 parathyroid fragments (PTx-AT90 ) and were followed for 12 months. We analyzed the expression of proliferating cell nuclear antigen (PCNA), calcium-sensing receptor (CasR), vitamin D receptor (VDR), fibroblast growth factor receptor-1 (FGFR1), sodium-dependent phosphate cotransporter-1 (PIT1), and Klotho in parathyroid glands., Results: Baseline median serum intact parathyroid hormone (iPTH) levels were 1,466 (1,087-2,125) pg/mL; vascular calcification scores correlated with serum iPTH (r = 0.529; P = .002) and serum phosphate levels (r = 0.389; P = .028); and Klotho expression was negatively correlated with serum phosphate levels (r = -0.4; P = .01). After 12 months, serum iPTH and alkaline phosphatase levels were significantly controlled in all groups, as was bone pain. The proportions of patients with serum iPTH levels within the ranges recommended by Kidney Disease: Improving Global Outcomes were similar among the treatment groups. During the hungry bone disease (HBS), patients received 3,786 g (1,412-7,580) of elemental calcium, and a trend toward a positive correlation between the cumulative calcium load at the end of follow up and VC score post-PTx was noted (r = 0.390; P = .06). Two cases evolved to clinically uncontrolled hyperparathyroidism in the sub-PTx group. The expression patterns of PCNA, VDR, CasR, PIT1, FGFR1, and Klotho in parathyroid glands did not correlate with serum systemic iPTH levels or the duration of HBS., Conclusions: All 3 operative techniques were effective at controlling rSHP, both in clinical and laboratory terms. Neither the quantity nor quality of parathyroid fragments influenced serum systemic iPTH and AT-iPTH levels. The cumulative calcium load appeared to correlate with the VC score and may have affected its progression. The effects of phosphate restriction on Klotho expression in human parathyroid glands and the subsequent decrease in FGF23 resistance must be addressed in further studies., (Copyright © 2017 Elsevier Inc. All rights reserved.)- Published
- 2018
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28. Methamidophos, an Organophosphorus Insecticide, Induces Pro-aggressive Behaviour in Mice.
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do Nascimento CP, Maretto GX, Marques GLM, Passamani LM, Abdala AP, Schenberg LC, Beijamini V, and Sampaio KN
- Subjects
- Acetylcholinesterase metabolism, Aggression physiology, Animals, Brain drug effects, Brain enzymology, Butyrylcholinesterase blood, Injections, Intraperitoneal, Male, Mice, Motor Activity drug effects, Motor Activity physiology, Psychological Tests, Social Isolation, Aggression drug effects, Insecticides toxicity, Organothiophosphorus Compounds toxicity
- Abstract
Although evidence indicates that exposure to organophosphorus (OP) pesticides induces neurobehavioral disorders, little is known about the effects of OP on aggressive behaviour. Our study investigated the effects of repeated exposure to an OP pesticide, methamidophos, on the isolation-induced aggressive behaviour in mice. Forty seven male mice were individually housed for a month. Socially isolated animals were then confronted with a standard non-isolated opponent for 15 min (pre-treatment trial), and the latency and frequency of aggressive and general exploratory behaviours were recorded. Based on the presence of attack behaviour in the pre-treatment trial, mice were classified as isolation-induced aggressive and non-aggressive. All mice were then treated for 7 days with methamidophos (3.5 mg/kg/day, n = 22, intraperitoneal (i.p.)) or saline (1 mL/kg/day, control group, n = 25, i.p.), and a second trial was performed. Repeated exposure to methamidophos induced attack behaviour in non-aggressive mice. The treatment with methamidophos also decreased plasma butyrylcholinesterase and brain acetylcholinesterase activity. These results suggest that methamidophos has a pro-aggressive effect on socially isolated mice.
- Published
- 2017
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29. Ontogenic behavioral consistency, individual variation and fitness consequences among lady beetles.
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Rodrigues AS, Botina L, Nascimento CP, Gontijo LM, Torres JB, and Guedes RN
- Subjects
- Age Factors, Animals, Behavior, Animal classification, Brazil, Aggression physiology, Behavior, Animal physiology, Coleoptera physiology, Insecticide Resistance physiology, Larva physiology
- Abstract
The potential relevance of complete metamorphosis for the individual variation in sets of behavioral traits and their fitness consequences in predatory species led to the present study. A set of nine behavioral traits were assessed for the larvae and adults of a pyrethroid-resistant and a susceptible population of the lady beetle Eriopis connexa. The aim was to assess: 1) the average individual behavioral (pheno)types and their within-population variation, 2) their ontogenic behavioral consistency from larva to adult, and 3) whether the observed correlated sets of behavioral traits can impact fitness. The average behavioral type differed between populations. The pyrethroid-resistant population consistently exhibited lower aggressiveness (as larvae) and exploration, but showed higher activity, as well as larva sociality, and sometimes boldness than the susceptible population. Behavioral trait variation was higher among pyrethroid-resistant individuals, particularly during the larval stage, but there was significant behavior correlation between larvae and adults, regardless of the insect population. Reduced aggressiveness, and to a lesser extent intermediate levels of boldness against heterospecific individuals were associated with higher population growth. Besides shedding light on the ontogenic consistency of behavioral traits and their fitness impact, our results also suggest that reduced aggressiveness is associated with predator population increase, but may compromise its effectiveness as a biocontrol agent., (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Published
- 2016
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30. The deceptive concept of hypoparathyroidism and recurrence after parathyroidectomy in dialysis patients: are we offering a Procrustean bed to some patients?
- Author
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Montenegro FL, Brescia MD, Nascimento CP Júnior, Massoni LM Neto, Arap SS, Santos SR, Goldenstein PT, Bueno RO, Custodio MR, Jorgetti V, and Moyses RM
- Subjects
- Adolescent, Adult, Child, Female, Humans, Hypoparathyroidism blood, Male, Parathyroid Hormone blood, Recurrence, Retrospective Studies, Young Adult, Hypoparathyroidism surgery, Parathyroidectomy, Renal Dialysis
- Abstract
Objective:: to analyze the frequency of hypoparathyroidism and of its recurrence after parathyroidectomy in dialysis patients according to different existing classifications., Methods:: we conducted a retrospective study of 107 consecutive dialysis patients undergoing total parathyroidectomy with immediate autograft in a tertiary hospital from 2006 to 2010. We studied the changes in PTH levels in the postoperative period over time. Were grouped patients according to different PTH levels targets recommended according to the dosage method and by the American and Japanese Nephrology Societies, and by an International Experts Consortium., Results:: after parathyroidectomy, there was sustained reduction in serum calcium and phosphatemia. The median value of PTH decreased from 1904pg/ml to 55pg/ml in 12 months. Depending on the considered target level, the proportion of patients below the target ranged between 17% and 87%. On the other hand, the proportion of patients with levels above the target ranged from 3% to 37%., Conclusion:: the application of different recommendations for PTH levels after parathyroidectomy in dialysis patients may lead to incorrect classifications of hypoparathyroidism or recurrent hyperparathyroidism and resultin discordant therapeutic conducts., Objetivo:: analisar as frequências de hipoparatireoidismo e de recidiva do hiperparatireoidismo após paratireoidectomia em pacientes dialíticos de acordo com diferentes classificações existentes., Métodos:: estudo retrospectivo de 107 pacientes dialíticos consecutivamente submetidos à paratireoidectomia total com autoenxerto imediato em um hospital terciário no período de 2006 a 2010. A variação dos níveis de PTH no pós-operatório foi estudada ao longo do tempo. Os pacientes foram agrupados de acordo com diferentes metas de níveis de PTH recomendados de acordo com o método de dosagem e pelas sociedades de nefrologia americana, japonesa e de um consórcio internacional de especialistas., Resultados:: após a paratireoidectomia, houve redução sustentada da calcemia e fosfatemia. O valor mediano do PTH reduziu-se de 1904pg/ml para 55pg/ml, em 12 meses. Dependendo do nível alvo considerado, a proporção de pacientes abaixo da meta variou entre 17% e 87%. Ao contrário, a proporção de pacientes com níveis acima da meta variou de 3% a 37%., Conclusão:: O emprego de diferentes recomendações de níveis de PTH em pacientes dialíticos após paratireoidectomia pode levar a classificações incorretas de hipoparatireoidismo ou hiperparatireoidismo recidivado e implicar em condutas terapêuticas discordantes.
- Published
- 2016
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31. Acute exposure to the insecticide O,S-dimethyl phosphoramidothioate (methamidophos) leads to impairment of cardiovascular reflexes in rats.
- Author
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Maretto GX, do Nascimento CP, Passamani LM, Schenberg LC, de Andrade TU, Figueiredo SG, Mauad H, and Sampaio KN
- Subjects
- Animals, Blood Pressure drug effects, Dose-Response Relationship, Drug, Lethal Dose 50, Male, Rats, Rats, Wistar, Reflex, Cardiovascular System drug effects, Insecticides toxicity, Organothiophosphorus Compounds toxicity
- Abstract
Poisoning by organophosphorus insecticides is often accompanied by cardiac complications which may be serious and even fatal. However, the effects of these compounds on the cardiovascular mechanisms involved in blood pressure regulation are not known. The aim of this study was to evaluate the effects of a sublethal dose (8 mg/kg, i.p.) of the organophosphorus methamidophos on chemoreceptor (CR) and Bezold-Jarisch (BJR) cardiovascular reflexes. Male Wistar rats were treated with single intraperitoneal injections of methamidophos in saline (n=23) or saline (0.9 percent, n=20) and underwent catheterization of femoral artery and vein one day after the injections. Cardiovascular recordings were performed 24h after the catheterization procedure. Plasma cholinesterase (ChE) activity was measured 24h after similar treatments in separate groups (n=10/group). The bradycardic component of CR and BJR was significantly attenuated in animals treated with methamidophos. The ChE activity was 80 percent reduced in the methamidophos-treated animals. Methamidophos impairment of the bradycardic component of two important cardiovascular reflexes may contribute to the cardiovascular toxicity associated with acute organophosphorus insecticides exposure., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
32. Evaluation of processing methods to equitably aliquot sputa for mycobacterial testing.
- Author
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Hadad DJ, Morais CG, Vinhas SA, Fennelly KP, Dietze R, Nascimento CP, and Palaci M
- Subjects
- Adolescent, Adult, Aged, Bacterial Load, Humans, Middle Aged, Tuberculosis, Pulmonary microbiology, Young Adult, Mycobacterium tuberculosis, Specimen Handling methods, Sputum microbiology, Tuberculosis, Pulmonary diagnosis
- Abstract
We compared bacillary loads after splitting sputum specimens by chemical (N-acetyl-l-cysteine [NALC]) and mechanical homogenization by vortexing with sterile glass beads. NALC and vortexing with glass beads were equally effective at homogenizing sputum specimens, resulting in an equal distribution of tubercle bacilli in the aliquots.
- Published
- 2012
- Full Text
- View/download PDF
33. Total parathyroidectomy in a large cohort of cases with hyperparathyroidism associated with multiple endocrine neoplasia type 1: experience from a single academic center.
- Author
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Montenegro FL, Lourenço DM Jr, Tavares MR, Arap SS, Nascimento CP Jr, Massoni Neto LM, D'Alessandro A, Toledo RA, Coutinho FL, Brandão LG, de Britto e Silva Filho G, Cordeiro AC, and Toledo SP
- Subjects
- Female, Follow-Up Studies, Humans, Hyperparathyroidism, Primary etiology, Male, Multiple Endocrine Neoplasia Type 1 complications, Parathyroid Glands transplantation, Parathyroid Neoplasms complications, Recurrence, Reoperation, Transplantation, Autologous, Hyperparathyroidism, Primary surgery, Multiple Endocrine Neoplasia Type 1 surgery, Parathyroid Neoplasms surgery, Parathyroidectomy methods
- Abstract
Most cases of sporadic primary hyperparathyroidism present disturbances in a single parathyroid gland and the surgery of choice is adenomectomy. Conversely, hyperparathyroidism associated with multiple endocrine neoplasia type 1 (hyperparathyroidism/multiple endocrine neoplasia type 1) is an asynchronic, asymmetrical multiglandular disease and it is surgically approached by either subtotal parathyroidectomy or total parathyroidectomy followed by parathyroid auto-implant to the forearm. In skilful hands, the efficacy of both approaches is similar and both should be complemented by prophylactic thymectomy. In a single academic center, 83 cases of hyperparathyroidism/ multiple endocrine neoplasia type 1 were operated on from 1987 to 2010 and our first surgical choice was total parathyroidectomy followed by parathyroid auto-implant to the non-dominant forearm and, since 1997, associated transcervical thymectomy to prevent thymic carcinoid. Overall, 40% of patients were given calcium replacement (mean intake 1.6 g/day) during the first months after surgery, and this fell to 28% in patients with longer follow-up. These findings indicate that several months may be needed in order to achieve a proper secretion by the parathyroid auto-implant. Hyperparathyroidism recurrence was observed in up to 15% of cases several years after the initial surgery. Thus, long-term follow-up is recommended for such cases. We conclude that, despite a tendency to subtotal parathyroidectomy worldwide, total parathyroidectomy followed by parathyroid auto-implant is a valid surgical option to treat hyperparathyroidism/multiple endocrine neoplasia type 1. Larger comparative systematic studies are needed to define the best surgical approach to hyperparathyroidism/multiple endocrine neoplasia type 1.
- Published
- 2012
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34. [Functional results of parathyroid autotransplantation in one single pocket for treatment of secondary hyperparathyroidism].
- Author
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Caliseo CT, Santos SR, Nascimento CP Jr, Arap SS, Brandão LG, and Montenegro FL
- Subjects
- Case-Control Studies, Female, Humans, Longitudinal Studies, Male, Parathyroid Glands physiology, Transplantation, Autologous methods, Hyperparathyroidism, Secondary surgery, Parathyroid Glands transplantation
- Abstract
Objective: To evaluate the operation and surgical time of autotransplanted parathyroid in a single site comparing it to the implant performed in five and twenty locations., Methods: Patients who underwent total parotidectomy with auto implant (Ptx-AI) for secondary and tertiary hyperparathyroidism were evaluated in groups of 20 implant sites (A), 5 sites (B) and single site (C), compared as for Functional Status (FE) of the implant and the surgical time of the procedure. Four functional states were determined according to the systemic level of PTH: 1-below normal, 2-normal, 3-high, no more than three times and 4 - more than three times higher., Results: There were 349 patients subjected to Ptx-AI for renal hyperparathyroidism from 1994 to 2009. For the functional study, 101 patients were eligible for the following observations: group A (n = 30) - 16.6% EF1, 50% EF2, 23.3% EF3 and 10%EF4; group B (n = 41) - 14.6% EF1, 58.5% EF2, 22% EF3 and 4.9% EF4; Group C (n = 30) - 17% EF1, 57% EF2, 20%EF3 and 6% EF4 (p = 0.9, x²). But in group C the mean operative time of implant was statistically lower (7.9 minutes) compared to the average of 5 site (18.6 minutes) and 20-site (44 minutes) implants in 66 evaluated patients (p<0,0001, ANOVA)., Conclusion: The self-implantation in a single site decreases the operative time without changing its functionality.
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- 2011
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35. Biolistic-mediated genetic transformation of cowpea (Vigna unguiculata) and stable Mendelian inheritance of transgenes.
- Author
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Ivo NL, Nascimento CP, Vieira LS, Campos FA, and Aragão FJ
- Subjects
- Acetolactate Synthase genetics, Biolistics, DNA, Plant genetics, Fabaceae drug effects, Genes, Reporter, Imidazoles pharmacology, Microscopy, Electron, Niacin analogs & derivatives, Niacin pharmacology, Plants, Genetically Modified drug effects, Tissue Culture Techniques, Transgenes, Fabaceae genetics, Inheritance Patterns, Plants, Genetically Modified genetics, Transformation, Genetic
- Abstract
We describe a novel system of exploiting the biolistic process to generate stable transgenic cowpea (Vigna unguiculata) plants. The system is based on combining the use of the herbicide imazapyr to select transformed meristematic cells after physical introduction of the mutated ahas gene (coding for a mutated acetohydroxyacid synthase, under control of the ahas 5' regulatory sequence) and a simple tissue culture protocol. The gus gene (under control of the act2 promoter) was used as a reporter gene. The transformation frequency (defined as the total number of putative transgenic plants divided by the total number of embryonic axes bombarded) was 0.90%. Southern analyses showed the presence of both ahas and gus expression cassettes in all primary transgenic plants, and demonstrated one to three integrated copies of the transgenes into the genome. The progenies (first and second generations) of all self-fertilized transgenic lines revealed the presence of the transgenes (gus and ahas) co-segregated in a Mendelian fashion. Western blot analysis revealed that the GUS protein expressed in the transgenic plants had the same mass and isoelectric point as the bacterial native protein. This is the first report of biolistic-mediated cowpea transformation in which fertile transgenic plants transferred the foreign genes to next generations following Mendelian laws.
- Published
- 2008
- Full Text
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36. [Gender and night work: sleep, daily life and the experiences of night shift workers].
- Author
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Rotenberg L, Portela LF, Marcondes WB, Moreno C, and Nascimento CP
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- Adaptation, Physiological physiology, Adult, Female, Humans, Interpersonal Relations, Male, Marital Status, Middle Aged, Occupational Health, Sleep Disorders, Circadian Rhythm epidemiology, Circadian Rhythm physiology, Human Activities, Sex Factors, Sleep physiology, Work Schedule Tolerance physiology, Work Schedule Tolerance psychology
- Abstract
This paper deals with the impact of night work from a gender perspective, through a field study at a factory employing men and women on the night shift. It is based on data for hours of sleep over the course of several weeks, socio-demographic data, and job information, using a semi-structured interview. The methodology includes chronobiological aspects of sleep (mainly quantitative data) and workers' discourse concerning gender-related experiences in the day-to-night switch. Despite gender issues and differences in daily life, the switch is perceived quite vividly by both men and women, permeating several aspects of life, like health, leisure, studies, and intimate personal relations. Quantitative sleep analysis showed more severe effects of night work on women, especially those with children. Such sleep patterns were associated with different expectations among men and women, revealing gender issues that are essential for understanding the reality of individuals who work odd hours.
- Published
- 2001
- Full Text
- View/download PDF
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