ALEXANDRE LEME GODOY DOS SANTOS
Projetos de Pesquisa
Unidades Organizacionais
Instituto de Ortopedia e Traumatologia, Hospital das Clínicas, Faculdade de Medicina
LIM/41 - Laboratório de Investigação Médica do Sistema Músculoesquelético, Hospital das Clínicas, Faculdade de Medicina
LIM/41 - Laboratório de Investigação Médica do Sistema Músculoesquelético, Hospital das Clínicas, Faculdade de Medicina
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- ER PvuII and XbaI polymorphisms in postmenopausal women with posterior tibial tendon dysfunction: a case control study(2018) PONTIN, P. A.; NOGARA, P. R. B.; FONSECA, F. C. P.; NETTO, C. Cesar; CARVALHO, K. C.; SOARES JUNIOR, J. M.; BARACAT, E. C.; FERNANDES, T. D.; MAFFULLI, N.; SANTOS, M. C. L.; GODOY-SANTOS, A. L.BackgroundPosterior tibial tendon (PTT) insufficiency is considered as the main cause of adult acquired flat foot and is three times more frequent in females. High estrogen levels exert a positive effect on the overall collagen synthesis in tendons. We have previously demonstrated the association between some genetic single-nucleotide polymorphism (SNP) and tendinopathy. In the present study, we investigated the association of PvuII c454-397T>C (NCBI ID: rs2234693) and XbaI c454-351A>G (NCBI ID: rs9340799) SNPs in estrogen receptor alfa (ER-) gene with PPT dysfunction.MethodsA total of 92 female subjects with PTT dysfunction, with histopathological examination of the tendon and magnetic resonance image (MRI) evidence of tendinopathy, were compared to 92 asymptomatic females who presented an intact PPT at MRI for PvuII and XbaI SNPs in the ER- gene. Genomic DNA was extracted from saliva and genotypes were obtained by polymerase chain reaction restriction fragment length polymorphism.ResultsThe analysis of PvuII SNPs showed no significant differences in the frequency of alleles and genotypes between control and PTT dysfunction groups. The XbaI SNPs in the ER- gene showed significant differences in the frequency of genotypes between control and test groups (p=0.01; OR 95% 1.14 (0.55-2.33).ConclusionsThe XbaI SNP in the ER gene may contribute to tendinopathy, and the A/A genotype could be a risk factor for PTT tendinopathy in this population. The PvuII SNP studied was not associated with PTT tendinopathy.
- EPIDEMIOLOGICAL STUDY ON LISFRANC INJURIES(2017) SOBRADO, Marcel Faraco; SAITO, Guilherme Honda; SAKAKI, Marcos Hideyo; PONTIN, Pedro Augusto; SANTOS, Alexandre Leme Godoy dos; FERNANDES, Tulio DinizObjective: To analyze the characteristics of patients with Lisfranc injuries and their associated fractures. Methods: This is a retrospective analysis on 42 patients with Lisfranc injuries hospitalized at Instituto de Ortopedia e Traumatologia do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, between 2006 and 2010. Parameters on patient profile, risk factors, fracture characteristics, data on treatment and acute complications were analyzed. Results: Analysis of 42 cases showed that in our sample, men were more affected than women, with a ratio of 4.25:1. The most frequent trauma mechanism was car accident, followed by motorcycle accident. The most frequent type of injury was isolated lesion type B of Quenu and Kuss classification, representing 50% of cases. The most common fracture on the sample was the second metatarsal bone, with 16 cases, followed by cuboid bone fracture. Among the 42 cases, 17% had exposed fractures and 33 patients presented other associated fractures. The mean time elapsed between the trauma and definitive treatment was 6.7 days, while the mean length of hospital stay was 13.8 days. Six patients presented acute postoperative complications. Conclusion: Lisfranc injuries are more common in men undergoing automobile trauma. The prevalence of associated fractures is a frequent finding and the hospital stay may be longstanding.
- EPIDEMIOLOGIC STUDY OF ANKLE FRACTURES IN A TERTIARY HOSPITAL(2014) SAKAKI, Marcos Hideyo; MATSUMURA, Bruno Akio Rodrigues; DOTTA, Thiago De Angelis Guerra; PONTIN, Pedro Augusto; SANTOS, Alexandre Leme Godoy dos; FERNANDES, Tulio DinizObjectives: To evaluate the epidemiology of ankle fractures surgically treated at the Instituto de Ortopedia e Traumatologia do Hospital das Clinicas da Universidade de Sao Paulo. Methods: Medical records of patients admitted with foot and ankle fractures between 2006 and 2011 were revised. Seventy three ankle fractures that underwent surgical treatment were identified. The parameters analyzed included age, gender, injured side, AO and Gustilo & Anderson classification, associated injuries, exposure, need to urgent treatment, time to definitive treatment and early post-operative complications. Study design: retrospective epidemiological study. Results: Male gender was predominant among subjects and the mean age was 27.5 years old. Thirty nine fractures resulted from traffic accidents and type B fracture according to AO classification was the most common. Twenty one were open fractures and 22 patients had associated injuries. The average time to definitive treatment was 6.5 days. Early post-operative complications were found in 21.3% of patients. Conclusions: Ankle fractures treated in a tertiary hospital of a large city in Brazil affect young people victims of high-energy accidents and present significant rates of associated injuries and post-operative complications.
- Matrix metalloproteinase-1 (MMP-1) and (MMP-8) gene polymorphisms promote increase and remodeling of the collagen III and V in posterior tibial tendinopathy(2018) DINIZ-FERNANDES, Tulio; GODOY-SANTOS, Alexandre Leme; SANTOS, Maria Cristina; PONTIN, Pedro; PEREIRA, Caio Augusto Alves; JARDIM, Yuri Justi; VELOSA, Ana Paula Pereira; MAFFULLI, Nicola; TEODORO, Walcy Rosolia; CAPELOZZI, Vera LuizaPosterior tibial tendinopathy (PTT) can lead to acquired flatfoot in adults. Many patients develop PTT without any identifiable risk factors. Molecular changes in extracellular matrix (ECM) and matrix metalloproteinase (MMP) polymorphism may influence the risk of developing PTT. We aim to investigate the association between matrix metalloproteinase-1 (MMP-1) and (MMP-8) gene polymorphisms with changes in collagen I, III and V in PTT. A case-control study with 22 patients and 5 controls was performed. The MMP-1 (2G/2G) and MMP-8 (T/T) genotypes were determined by PCR-restriction fragment length polymorphism. Tendon specimens were evaluated by a histologic semiquantitative score, immunofluorescence and histomorphometry for collagen I, III and V. Tendon specimens from PTT demonstrated marked distortion of the architecture with necrosis, large basophilic areas with disruption of the normal linear orientation of collagen bundles, infiltration of inflammatory cells, dystrophic calcification and ossification. Under immunofluorescence, PTT tendon specimens showed weak green fluorescence and diffuse distribution of collagen I fibers, but strong fluorescence of collagen III and V. The collagen I fibers were significantly decreased whereas an increase of collagen III and V were found in PTT compared to control groups. In addition, PTT group presented a significant association with MMP-1 and MMP-8 gene polymorphisms. Patients with PTT matrix metalloproteinase-1 (MMP-1) and (MMP-8) gene polymorphisms presented an increase of the collagen III and V ratio, suggesting that the higher proportion in degenerated tendons could contribute to a decrease in the mechanical resistance of the tissue. Still, functional and association studies are needed to elucidate evident roles of MMPs in PTT.
- Novel animal model for Achilles tendinopathy: Controlled experimental study of serial injections of collagenase in rabbits(2018) NETTO, Cesar de Cesar; GODOY-SANTOS, Alexandre Leme; PONTIN, Pedro Augusto; NATALINO, Renato Jose Mendonca; PEREIRA, Cesar Augusto Martins; LIMA, Francisco Diego de Oliveira; FONSECA, Lucas Furtado da; STAGGERS, Jackson Rucker; CAVINATTO, Leonardo Muntada; SCHON, Lew Charles; CAMARGO, Olavo Pires de; FERNANDES, Tulio DinizOur goal was to develop a novel technique for inducing Achilles tendinopathy in animal models which more accurately represents the progressive histological and biomechanical characteristic of chronic Achilles tendinopathy in humans. In this animal research study, forty-five rabbits were randomly assigned to three groups and given bilateral Achilles injections. Low dose (LD group) (n = 18) underwent a novel technique with three low-dose (0.1mg) injections of collagenase that were separated by two weeks, the high dose group (HD) (n = 18) underwent traditional single high-dose (0.3mg) injections, and the third group were controls (n = 9). Six rabbits were sacrificed from each experimental group (LD and HD) at 10, 12 and 16 weeks. Control animals were sacrificed after 16 weeks. Histological and biomechanical properties were then compared in all three groups. At 10 weeks, Bonar score and tendon cross sectional area was highest in HD group, with impaired biomechanical properties compared to LD group. At 12 weeks, Bonar score was higher in LD group, with similar biomechanical findings when compared to HD group. After 16 weeks, Bonar score was significantly increased for both LD group (11,8 +/- 2,28) and HD group (5,6 +/- 2,51), when compared to controls (2 +/- 0,76). LD group showed more pronounced histological and biomechanical findings, including cross sectional area of the tendon, Young's modulus, yield stress and ultimate tensile strength. In conclusion, Achilles tendinopathy in animal models that were induced by serial injections of low-dose collagenase showed more pronounced histological and biomechanical findings after 16 weeks than traditional techniques, mimicking better the progressive and chronic characteristic of the tendinopathy in humans.
- Association of estrogen receptor beta polymorphisms with posterior tibial tendon dysfunction(2020) NOGARA, P. R. B.; GODOY-SANTOS, A. L.; FONSECA, F. C. P.; CESAR-NETTO, C.; CARVALHO, K. C.; BARACAT, E. C.; MAFFULLI, N.; PONTIN, P. A.; SANTOS, M. C. L.Posterior tibial tendon (PTT) dysfunction is three times more common in females, and some patients may have a predisposition without a clinically evident cause, suggesting that individual characteristics play an important role in tendinopathy. The present study investigated the association of rs4986938 (+ 1730G > A; AluI RFLP) and rs1256049 (- 1082G > A; RsaI RFLP) single nucleotide polymorphisms (SNPs) of estrogen receptor-beta (ER-beta) gene with PTT dysfunction. A total of 400 participants were recruited. The PTT dysfunction group: these patients underwent surgery, with PTT tendinopathy confirmed by histopathology and magnetic resonance image (MRI). The control group was composed of participants with no clinical or MRI evidence of PTT dysfunction. Each group was composed of 100 postmenopausal women, 50 premenopausal women, and 50 men. Genomic DNA was extracted from saliva samples, and genotypes were obtained by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Concerning theER-beta SNP rs4986938, there were significant differences in the frequencies of alleles between test and control groups of all the cases, only postmenopausal women and only men (p < 0.0001,p = 0.0016 andp = 0.0001). Considering the PTT dysfunction group and comparing postmenopausal women versus premenopausal women adding men, the analysis showed significant differences in the allelic distribution (p = 0.0450): the allele A in postmenopausal women is a risk factor. TheER-beta SNP rs1256049 did not show differences in the frequencies of alleles and genotypes between groups. TheER-beta SNP rs4986938, but not ER -beta SNPs rs1256049, may contribute to PTT insufficiency in the Brazilian population, with additional risk in postmenopausal women. Addition, in men the genetic factor could be more determinant.