Association between col1a2 polymorphism and the occurrence of pelvic organ prolapse in Brazilian women / Associação entre polimorfismo do gene col1a2 e a ocorrência do prolapso de órgãos pélvicos em mulheres brasileiras

Abstract Objective To evaluate the rs42524 polymorphism of the procollagen type I alpha (α) 2 (COL1A2) gene as a factor related to the development of pelvic organ prolapse (POP) in Brazilian women. Methods The present study involved 112 women with POP stages III and IV (case group) and 180 women with POP stages zero and I (control group). Other clinical data were obtained by interviewing the patients about their medical history, and blood was also collected from the volunteers for the extraction of genomic DNA. The promoter region of the COL1A2 gene containing the rs42524 polymorphism was amplified, and the discrimination between the G and C variants was performed by digestion of the polymerase chain reaction (PCR) products with the MspA1I enzyme followed by agarose gel electrophoresis analysis. Results A total of 292 women were analyzed. In the case group, 71 had the G/G genotype, 33 had the G/C genotype, and 7 had the C/C genotype. In turn, the ratio in the control group was 117 G/G, 51 G/C, and 11 C/C. There were no significant differences between the groups. Conclusion Our data did not show an association between the COL1A2 polymorphism and the occurrence of POP.

Resumo Objetivo Avaliar o polimorfismo rs42524 do gene pró-colágeno tipo I alfa (α) 2 (COL1A2) como fator relacionado ao desenvolvimento de prolapso de órgãos pélvicos (POP) em mulheres brasileiras. Métodos O estudo envolveu 112 mulheres com POP nos estádios III e IV (grupo caso) e 180 mulheres com POP nos estádios zero e I (grupo controle). Outros dados clínicos foramobtidos pormeio de entrevistas comas pacientes sobre seu históricomédico, e o sangue das voluntárias também foi coletado para extração de DNA genômico. A região promotora do gene COL1A2 contendo o polimorfismo rs42524 foi amplificada, e a discriminação entre as variantes G e C foi realizada por digestão dos produtos de reação em cadeia da polimerase (RCP) com a enzima MspA1I, seguida de análise por eletroforese em gel de agarose. Resultados Foram analisadas 292 mulheres. No grupo caso, 71 tinham o genótipo G/G, 33 tinham o genótipo G/C, e 7 tinham o genótipo C/C. Por sua vez, a relação no grupo controle foi de 117 G/G, 51 G/C e 11 C/C. Não houve diferenças significativas entre os grupos. Conclusão Nossos dados não mostraram associação do polimorfismo do gene COL1A2 com a ocorrência de POP.

Exogenous pulmonary surfactant prevents the development of intra-abdominal adhesions in rats.

Intra-abdominal adhesions are major post-operative complications for which no effective means of prevention is available. We aimed to evaluate the efficacy of exogenous pulmonary surfactant administration in the prevention of post-operative abdominal adhesions. Rats were randomly assigned to undergo laparotomy (L) or gastroenterostomy (GE) and then treated with surfactant (groups L-S and GE-S, respectively). Intra-abdominal adhesions, collagen fibre content, metalloproteinase (MMP)-9, expression of growth factors (TGF-ß, KGF and VEGF), type III procollagen (PCIII) and pro-caspase 3, as well as isolectin B4 and ED1-positive cells expressing MMP-9, were evaluated. Groups treated with surfactant (GE-S and L-S) exhibited fewer adhesions. A significant reduction in collagen fibre content was observed in GE-S compared to GE animals (P < 0.001). In situ and gelatin zymography analysis showed higher MMP-9 expression and activity in the GE-S group compared to the GE group (P < 0.05). ED1-positive cell counts were significantly higher in the GE-S group (P < 0.001) than in the GE group. Virtually all cells positive for ED1 were MMP-9+. Double-labelling of MMP-9 with IB4 showed no significant differences between GE-S and GE groups. TGF-ß, KGF, PCIII and pro-caspase-3 mRNA expression decreased significantly in GE-S compared to GE animals (P < 0.05). Surfactant administration also reduced apoptosis in the GE-S group. These findings suggest that surfactant reduces the intra-abdominal adhesions triggered by laparotomy and gastrointestinal anastomosis, thus preventing fibrosis formation at the peritoneal surfaces. This preclinical study suggests an innovative treatment strategy for intra-abdominal adhesions with surfactant and to endorse its putative mechanism of action.

Viabilidade da mensuração de marcadores de remodelação óssea em mulheres com lúpus eritematoso sistêmico / Feasibility of measurement of bone turnover markers in female patients with systemic lupus erythematosus

Objetivo: Investigar a viabilidade dos marcadores de remodelação óssea (MRO) na avaliação do metabolismo ósseo em pacientes com lúpus eritematoso sistêmico (LES), de acordo com as diretrizes da International Osteoporosis Foundation e da International Federation of Clinical Chemistry and Laboratory Medicine. Métodos: O estudo incluiu 43 pacientes do sexo feminino com LES. Foram medidos os níveis séricos de propeptídeo N-terminal do procolágeno tipo I (PINP), telopeptídeo C-terminal do colágeno tipo I (CTX), osteocalcina, HPT, 25(OH)D, anticorpos anticardiolipina, antidsDNA e antinucleossomo. Resultados: Os níveis de PINP e CTX estavam elevados em pacientes com LES com idade > 45, em comparação com aqueles com idade < 45 anos, embora com significância estatística limítrofe (p = 0,05). Foram encontradas correlações entre os MRO: a mais forte foi entre o PINP e a osteocalcina (τ = 0,69, p < 0,05). Encontrou-se que o PINP e a osteocalcina estão correlacionados com o HPT (τ = 0,3, τ = 0,29, respectivamente, p < 0,05). A idade estava correlacionada com o PINP (τ = 0,23, p < 0,05). Valores elevados de PINP foram encontrados em maior frequência do que valores elevados de osteocalcina ou CTX, tanto em pacientes com idade < 45 (p = 0,001) quanto > 45 (p < 0,001). Não houve diferença estatisticamente significativa nos níveis de PINP, osteocalcina ou CTX com relação à estação do ano, nem em todo o grupo de pacientes com LES, nem naqueles com mais ou menos de 45 anos. O uso prévio de glucocorticoides não esteve associado a diferenças nos MRO. Conclusões: O aumento nos MRO no LES parece refletir predominantemente o padrão de remodelação óssea relacionado com a idade. Pode-se esperar que o PINP aumentado seja o desfecho mais comumente encontrado entre os MRO. É necessário incluir melhores diagnósticos de distúrbios ósseos com MRO, feitos de acordo com as normas internacionais de referência, na abordagem de ...

Objective: To investigate the feasibility of bone turnover markers (BTMs) for the assessment of bone metabolism in patients with systemic lupus erythematosus (SLE), according to the guidelines of the International Osteoporosis Foundation and the International Federation of Clinical Chemistry and Laboratory Medicine. Methods: The study included 43 female SLE patients. Serum pro-collagen type I N propeptide (PINP), C-terminal telopeptide of type I collagen (CTX), osteocalcin, PTH, 25(OH)D, anti-cardiolipin, anti-dsDNA, and anti-nucleosome levels were measured. Results: PINP and CTX levels were elevated in SLE patients aged > 45 in comparison to those aged < 45, although with borderline significance (p = 0.05, respectively). Correlations were found between BTMs: the strongest being between PINP and osteocalcin (τ= 0.69, p < 0.05). PINP and osteocalcin were found to be associated with PTH (τ = 0.3, τ = 0.29, respectively, p < 0.05). Age correlated with PINP (τ= 0.23, p < 0.05). Elevated PINP was found more frequently than elevated osteocalcin or CTX, both in patients aged < 45 (p = 0.001) and > 45 (p < 0.001). No significant difference in PINP, osteocalcin or CTX levels was found with respect to season, neither in the entire SLE group, nor in the under-45 or over-45 groups. Previous glucocorticoid treatment was not associated with difference in BTMs. Conclusions: Increased BTMs in SLE appear to predominantly reflect the pattern of bone remodeling related to age. Increased PINP is expected to be the most frequent outcome among BTMs. Better diagnoses of bone disturbances with BTMs performed in accordance with international reference standards need to be included in the approach to SLE patients, in addition to bone mineral density assessment. .

Feasibility of measurement of bone turnover markers in female patients with systemic lupus erythematosus.

OBJECTIVE: To investigate the feasibility of bone turnover markers (BTMs) for the assessment of bone metabolism in patients with systemic lupus erythematosus (SLE), according to the guidelines of the International Osteoporosis Foundation and the International Federation of Clinical Chemistry and Laboratory Medicine. METHODS: The study included 43 female SLE patients. Serum procollagen type I N propeptide (PINP), C-terminal telopeptide of type I collagen (CTX), osteocalcin, PTH, 25(OH)D, anti-cardiolipin, anti-dsDNA, and anti-nucleosome levels were measured. RESULTS: PINP and CTX levels were elevated in SLE patients aged > 45 in comparison to those aged < 45, although with borderline significance (p = 0.05, respectively). Correlations were found between BTMs: the strongest being between PINP and osteocalcin (τ = 0.69, p < 0.05). PINP and osteocalcin were found to be associated with PTH (τ = 0.3, τ = 0.29, respectively, p < 0.05). Age correlated with PINP (τ = 0.23, p < 0.05). Elevated PINP was found more frequently than elevated osteocalcin or CTX, both in patients aged < 45 (p = 0.001) and > 45 (p < 0.001). No significant difference in PINP, osteocalcin or CTX levels was found with respect to season, neither in the entire SLE group, nor in the under-45 or over-45 groups. Previous glucocorticoid treatment was not associated with difference in BTMs. CONCLUSIONS: Increased BTMs in SLE appear to predominantly reflect the pattern of bone remodeling related to age. Increased PINP is expected to be the most frequent outcome among BTMs. Better diagnoses of bone disturbances with BTMs performed in accordance with international reference standards need to be included in the approach to SLE patients, in addition to bone mineral density assessment.

Procollagen Type I and III Aminoterminal Propeptide Levels and Severity of Interstitial Lung Disease in Mexican Women With Progressive Systemic Sclerosis.

BACKGROUND: Interstitial lung disease (ILD) is a frequent complication in progressive systemic sclerosis (SSc), being present in 25% to 90% of cases. OBJECTIVES: To evaluate whether serum levels of procollagen typei and iii aminoterminal propeptide (PINP and PIIINP) correlate with severity and patterns of ILD in Mexican women with SSc. METHODS: Thirty three SSc patients were assessed for disease characteristics and anti-topoisomerase antibodies (topoi), and also underwent pulmonary function tests and high-resolution computed tomography (HRCT). Nineteen patients had ILD+SSc, and 14 had no lung involvement (no ILD-SSc); data were compared with those from 45 healthy controls. PINP and PIIINP were assessed in all 3 groups. RESULTS: Patients with SSc had higher PINP and PIIINP vs controls (P=.001, P<.001, respectively). Compared to no ILD-SSc patients, those with ILD+SSc had longer disease duration in years (P=.005), higher modified Rodnan skin score (P<.001), higher Health Assessment Questionnaire-Disability-Index scores (P<.001), higher topoi U/mL (P<.001), PINP (49.28±28.63 vs. 32.12±18.58µg/L, P=.05), and PIIINP (4.33±1.03 vs. 2.67±1.26µg/L, P<.001) levels. ILD severity based on total HRCT correlated with PINP (r=.388, P=.03) and PIIINP (P=.594, P<.001). On adjusted analysis, ILD severity was associated with disease duration (P=.037), PIIINP (P=.038), and topoi (P=.045). CONCLUSIONS: PINP and PIIINP are useful markers for severe ILD+SSc, suggesting they could play a role in the follow-up of this complication in SSc.

Diagnóstico clínico e laboratorial do hiperparatiroidismo secundário / Clinical and laboratory diagnoses of secondary hyperparathyroidism

O hiperparatiroidismo secundário (HPTS), observado nos doentes urémicos, apesar de se instalar desde estadios precoces da insuficiência renal,apresenta manifestações clínicas pouco específicas e frequentemente tardias. Para além da promissora técnica de avaliação da arquitectura trabecularóssea por tomografia quantitativa microcomputorizada os métodos imagiológicos são de escassa utilidade no diagnóstico das alterações ósseasassociadas ao HPTS. Ao longo dos últimos anos foram avaliados diversos marcadores bioquímicos da remodelação óssea e a respectiva utilidade nodiagnóstico não invasivo da osteodistrofia renal. Finalmente, é ainda discutido o eventual papel de factores locais (citoquinas e factores de crescimento) na modulação da remodelação óssea.

Secondary hyperparathyroidism represents one extreme of the spectrum of the bone and endocrine changes observed in uraemic patients, and may develop since early stages of renal failure. The clinical symptoms and signs are non-specific and the contribution of image evaluation in the diagnosis of secondary hyperparathyroidism is, frequently, misleading. In this review, in addition to the classic modulators of bone remodeling, like parathyroid hormone (and PTHfragments), calcitriol and calcitonin, the role of others local factors involved in osteoblast and osteoclast activation, like cytokines and growth factors, is alsodiscussed.