LUIZ FERNANDO ONUCHIC
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
LIM/29 - Laboratório de Nefrologia Celular, Genética e Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/29 - Laboratório de Nefrologia Celular, Genética e Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder
8 resultados
Resultados de Busca
Agora exibindo 1 - 8 de 8
- Influence of androgenic blockade with flutamide on pain behaviour and expression of the genes that encode the NaV1.7 and NaV1.8 voltage-dependent sodium channels in a rat model of postoperative pain(2019) BARBOSA NETO, Jose Osvaldo; GARCIA, Joao Batista Santos; CARTAGENES, Maria do Socorro de Souza; AMARAL, Andressa Godoy; ONUCHIC, Luiz Fernando; ASHMAWI, Hazem AdelBackgroundExperimental studies suggest that testosterone reduces the nociceptive response after inflammatory and neuropathic stimuli, however the underlying mechanisms have not been fully elucidated. The aims of this study were to evaluate the effect of peripheral blockade of testosterone on pain behaviour and on expression levels of the genes that encode the NaV1.7 and NaV1.8 channels, in dorsal root ganglia in an acute postoperative pain model, as well as the influence of androgen blockade on the expression of these genes.MethodsPostoperative pain was induced by a plantar incision and the study group received flutamide to block testosterone receptor. The animals were submitted to behavioural evaluation preoperatively, 2h after incision, and on the 1st, 2nd, 3rd and 7th postoperative days. Von Frey test was used to evaluate paw withdrawal threshold after mechanical stimuli and the guarding pain test to assess spontaneous pain. The expression of the genes encoding the sodium channels at the dorsal root ganglia was determined by real time quantitative polymerase chain reaction.ResultsAnimals treated with flutamide presented lower paw withdrawal threshold at the 1st, 2nd, 3rd, and 7th postoperative days. The guarding pain test showed significant decrease in the flutamide group at 2h and on the 3rd and 7th postoperative days. No difference was detected between the study and control groups for the gene expression.ConclusionsOur data suggest an antinociceptive effect of androgens following plantar incision. The expression of genes that encode voltage-gated sodium channels was not influenced by androgen blockade.
- The immunohistological profile of membranous nephropathy associated with chronic Schistosoma mansoni infection reveals a glomerulopathy with primary features(2019) ARAUJO, Stanley de Almeida; NEVES, Precil Diego Miranda de Menezes; WANDERLEY, David Campos; REIS, Marlene Antonia dos; DIAS, Cristiane Bitencourt; MALHEIROS, Denise Maria Avancini Costa; ONUCHIC, Luiz Fernando
- Two cases of fungal cyst infection in ADPKD: is this really a rare complication?(2019) ONUCHIC, Laura; SATO, Victor Augusto Hamamoto; NEVES, Precil Diego Miranda de Menezes; BALBO, Bruno Eduardo Pedroso; PORTELA-NETO, Antonio Abel; FERREIRA, Fernanda Trani; WATANABE, Elieser Hitoshi; WATANABE, Andreia; ALMEIDA, Maria Claudia Stockler de; TESTAGROSSA, Leonardo de Abreu; CHOCAIR, Pedro Renato; ONUCHIC, Luiz FernandoBackground: Cyst infection is a prevalent complication in autosomal dominant polycystic kidney disease (ADPKD) patients, however therapeutic and diagnostic approaches towards this condition remain unclear. The confirmation of a likely episode of cyst infection by isolating the pathogenic microorganism in a clinical scenario is possible only in the minority of cases. The available antimicrobial treatment guidelines, therefore, might not be appropriate to some patients. Case presentation: We describe two unique cases of kidney cyst infection by Candida albicans, a condition that has not been previously described in literature. Both cases presented clear risk factors for Candida spp. infection. However, since there was no initial indication of cyst aspiration and culture, antifungal therapy was not immediately started and empirical treatment was initiated as recommended by the current guidelines. Antifungal treatment was instituted in both cases along the clinical course, according to their specificities. Conclusion: Our report highlights the possibility of Candida spp. cyst infection. Failure of clinical improvement with antibiotics should raise the suspicion of a fungal infection. Identification of infected cysts should be pursued in such cases, particularly with PET-CT, and when technically possible followed by cyst aspiration and culture to guide treatment. Risk factors for this condition, such as Candida spp. colonization, previous antimicrobial therapy, hemodialysis, necrotizing pancreatitis, gastrointestinal/hepatobiliary surgical procedure, central venous catheter, total parenteral nutrition, diabetes mellitus and immunodeficiency (neutropenia < 500 neutrophils/mL, hematologic malignancy, chemotherapy, immunosuppressant drugs), should be also considered accepted criteria for empirical antifungal therapy.
- Periostin and polycystic kidney disease: more pieces in the puzzle(2019) WATANABE, Elieser H.; AMARAL, Andressa G.; ONUCHIC, Luiz F.
- Concentration of Serum Vascular Endothelial Growth Factor (VEGF-D) and Its Correlation with Functional and Clinical Parameters in Patients with Lymphangioleiomyomatosis from a Brazilian Reference Center(2019) AMARAL, Alexandre Franco; OLIVEIRA, Martina Rodrigues de; DIAS, Olivia Meira; ARIMURA, Fabio Eiji; FREITAS, Carolina Salim Goncalves; ACENCIO, Milena Marques Pagliarelli; ALVARENGA, Vanessa Adelia de; KAIRALLA, Ronaldo Adib; CARVALHO, Carlos Roberto Ribeiro; BALDI, Bruno Guedes; SCLEROSIS, Tuberous; BALBO, Bruno Eduardo Pedroso; WATANABE, Elieser Hitoshi; SAMORANO, Luciana Paula; ONUCHIC, Luiz Fernando; RIVITTI-MACHADO, Maria Cecilia da Matta; MANREZA, Maria Luiza Giraldes de; CORDEIRO, Mauricio Dener; TAKAHASHI, Patricia; OLIVEIRA, Zilda Najjar Prado deIntroductionSerum vascular endothelial growth factor-D (VEGF-D) is a lymphangiogenic growth factor that is considered a valuable tool in the diagnosis of lymphangioleiomyomatosis (LAM). Previous studies have reported a wide variability in VEGF-D serum levels in LAM patients and it seems to be associated with pulmonary impairment and lymphatic involvement.MethodsWe conducted a cross-sectional study from 2009 to 2017 that evaluated VEGF-D serum levels in a cohort of LAM patients who were never treated with mTOR inhibitors and compared them to healthy age-matched volunteers. Clinical and functional parameters were assessed and correlated with their respective serum VEGF-D levels.ResultsOne hundred and four patients were included in the analysis. Serum VEGF-D levels were higher in LAM patients compared to healthy controls: 796 (404-1588) versus 162 (117-232)pg/mL, respectively (p<0.001). Patients with tuberous sclerosis complex-LAM, TSC-LAM (20%), had higher levels of VEGF-D when compared to patients with sporadic LAM (80%) [1005 (641-2732) vs. 772 (370-1383), p=0.05]. Serum VEGF-D levels were weakly correlated with DLCO (r=-0.26, p=0.001) and lymphatic involvement was more frequent in those with serum VEGF-D levels equal or above 800pg/mL (35% vs. 13%, p=0.02).ConclusionsIn LAM, serum VEGF-D is weakly associated with lung function impairment and strongly associated with lymphatic involvement. VEGF-D is validated for use in Brazilian patients with LAM whose characteristics must be accounted for when evaluating their serum VEGF-D levels.
- Age-based ultrasonographic criteria for diagnosis of autosomal dominant polycystic kidney disease in Persian cats(2019) GUERRA, Juliana M.; FREITAS, Mariana F.; DANIEL, Alexandre G. T.; PELLEGRINO, Arine; CARDOSO, Natalia C.; CASTRO, Isac de; ONUCHIC, Luiz F.; COGLIATI, BrunoObjectives The aim of this study was to establish ultrasound criteria for the diagnosis of autosomal dominant polycystic kidney disease (ADPKD) in Persian cats. Methods Eighty-two Persian cats were assessed using renal ultrasound and genotyped for the C -> A transversion in exon 29 of PKD1. The animals were also submitted to hematological characterization, serum biochemistry analyses and urinalysis. Results Age, sex and neutering status did not differ between ADPKD (n = 12) and non-ADPKD (n = 70) cats. After integrated molecular genetics/ultrasonographic analysis, the presence of at least one renal cyst was sufficient to establish a diagnosis of ADPKD in animals up to 15 months of age. Two or more cysts were required for diagnosis in cats aged 16-32 months, and at least three cysts warranted diagnosis of ADPKD in animals aged 33-49 months. Finally, four or more cysts led to diagnosis in cats aged 50-66 months. Although cats with ADPKD exhibited higher serum calcium levels than non-affected cats, hematological, urinalysis and other biochemical parameters did not differ between the two groups. Conclusions and relevance Integrated analyses of imaging and molecular genetics data enabled, for the first time, the establishment of age-based ultrasonographic criteria for the diagnosis of ADPKD in Persian cats. The development of imaging criteria is particularly relevant and useful in the clinical setting given the current limitations to access and the cost of molecular genetics-based diagnostic tests.
- Caffeine accelerates cystic kidney disease in a Pkd1-deficient mouse model(2019) MECA, R.; BALBO, B.E.; ORMANJI, M.S.; FONSECA, J.M.; IANNUZZI, L.R.; COSTA, E.S.; ONUCHIC, L.F.; HEILBERG, I.P.Background/Aims: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst formation and growth, leading to end-stage renal disease. A higher kidney volume is predictive of a more accelerated decline in renal function. This study aimed to examine the effects of caffeine, a phosphodiesterase inhibitor, on the progression of cystic kidney disease in a mouse model orthologous to human disease (Pkd1cond/cond:Nestincre). Methods: Caffeine was administered to male cystic (CyCaf) and noncystic (NCCaf) mice (Pkd1cond/cond) from conception and at the postweaning period through 12 weeks of life (3 mg/d), while control animals consumed water (CyCtrl and NCCtrl). Renal ultrasonography was performed at 10 weeks of life to calculate total kidney volume and cystic index. At the end of the protocol, blood and urine samples were collected for biochemical analysis, and animals were euthanized. Kidneys were harvested to obtain renal tissue for determinations of adenosine 3´5´-cyclic monophosphate (cAMP) by an enzymatic immunoassay kit and phosphorylated extracellular signal-regulated kinase (p-ERK) by Western blotting. Renal fibrosis (picrosirius staining), renal cell proliferation (ki-67 immunohistochemistry) and apoptotic rates (TUNEL analysis) were also determined. Results: At 12 weeks, CyCaf mice exhibited higher serum urea nitrogen, renal cystic index, total kidney volume, kidney cell proliferation, apoptosis and fibrosis compared with CyCtrl mice. Serum cystatin C was significantly higher in CyCaf than in NCCaf and NCCtrl mice. CyCaf mice had higher total kidney weight than all other groups but not higher heart and liver weight. The levels of cAMP and p-ERK did not differ among the groups. Conclusion: Caffeine consumption from conception through 12 weeks led to increased cystic index and total kidney volume and worsened renal function in Pkd1-deficient cystic mice, suggesting that high consumption of caffeine may contribute to a faster progression of renal disease in ADPKD. © 2019 The Author(s).
- A novel single amino acid deletion impairs fibronectin function and causes familial glomerulopathy with fibronectin deposits: case report of a family(2019) MONTEIRO, Maria Luiza Goncalves dos Reis; CUSTODIO, Fabiano Bichuette; NEVES, Precil Diego Miranda de Menezes; FERREIRA, Frederico Moraes; WATANABE, Elieser Hitoshi; LERARIO, Antonio Marcondes; ARAUJO, Liliane Silvano de; BALBO, Bruno Eduardo Pedroso; PINTO, Vivian Christine Dourado; BARBOSA, Livia Maria Gruli; MARQUES, Vilmar de Paiva; MACHADO, Juliana Reis; REIS, Marlene Antonia; ONUCHIC, Luiz FernandoBackground Glomerulopathy with fibronectin deposits is an autosomal dominant disease associated with proteinuria, hematuria, hypertension and renal function decline. Forty percent of the cases are caused by mutations in FN1, the gene that encodes fibronectin. Case presentation This report describes two cases of Glomerulopathy with fibronectin deposits, involving a 47-year-old father and a 14-year-old son. The renal biopsies showed glomeruli with endocapillary hypercellularity and large amounts of mesangial and subendothelial eosinophilic deposits. Immunohistochemistry for fibronectin was markedly positive. Whole exome sequencing identified a novel FN1 mutation that leads to an amino-acid deletion in both patients (Ile1988del), a variant that required primary amino-acid sequence analysis for assessment of pathogenicity. Our primary sequence analyses revealed that Ile1988 is very highly conserved among relative sequences and is positioned in a C-terminal FN3 domain containing heparin- and fibulin-1-binding sites. This mutation was predicted as deleterious and molecular mechanics simulations support that it can change the tertiary structure and affect the complex folding and its molecular functionality. Conclusion The current report not only documents the occurrence of two GFND cases in an affected family and deeply characterizes its anatomopathological features but also identifies a novel pathogenic mutation in FN1, analyzes its structural and functional implications, and supports its pathogenicity.