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Infantile cortical hyperostosis or Caffey disease is a rare genetic disorder caused by a mutation in the collagen 1 gene. The mechanism of the disease has not yet been fully elucidated, but the most important factor in the pathogenesis and the consequence of the mutation is periosteal inflammation. The disease becomes clinically evident during the first months of life with asymmetrical bone thickening, most commonly in the mandible, clavicle, scapula, ribs, and long bones. Non-specific systemic inflammatory symptoms can also be present. X-ray imaging with demonstration of bone hyperostosis is essential for the diagnosis, which is confirmed by genetic testing. Treatment is symptomatic. The prognosis of the disease depends on the mode of inheritance. The autosomal recessive form, known as the prenatal form, has a poor prognosis. The autosomal dominant form or infantile Caffey disease usually resolves spontaneously without consequences before the age of two years. We present a case of a neonate with Caffey disease with proven COL1A1 gene mutation.

Study Design: Retrospective study.Purpose: This study aimed to assess the effect of refilling with hydroxyapatite/collagen (HAp/Col) composite on an iliac crest defect after spinal fusion.Overview of Literature: The use of iliac crest bone graft has been the gold standard in spinal fusion for a long time because of its biological and non-immunologic properties. Few reports have addressed how bone defects recover after iliac crest bone harvest following spinal fusion.Methods: Cancellous bone was collected from the anterior iliac crest during lateral interbody fusion (LIF), and the bone void of the ilium was refilled with a porous HAp/Col composite. We assessed bone recovery using computed tomography (CT). From the 74 patients who underwent LIF between January 2015 and December 2016, we included 49 patients whose iliac crest could be evaluated using CT at 3 months and 1 year after the surgery.Results: Bone defects decreased in a time-dependent manner after the surgery. Cortical closure was observed in 28.5% of the cases 3 months after the surgery; at 1 year postoperatively, 95.9% of the patients had cortical closure. Complete repair of the cancellous bone was achieved in 57.1% of the patients at 3 months after the surgery and in 95.9% at 1 year after the surgery. There were no significant hematomas, infections, iliac crest fractures, or soft tissue herniation.Conclusions: Radiographic recovery of cortical and cancellous bone defects was achieved with high probability via refilling with HAp/Col composite over the 1-year period.

Osteogenesis imperfecta (OI) is a heritable bone dysplasia characterized by bone fragility and long bone deformities. Approximately 85% of OI cases are caused by dominant autosomal mutations in the type I collagen coding genes (COL1A1 and COL1A2), which affect the quantity or structure of collagen. The remaining percentage of cases is caused by mutation in the proteins responsible for posttranslational modification, processing and crosslinking of collagen, bone mineralization, and osteoblast differentiation. In the past decade, new recessive, dominant, and X-linked inheritance. As a result, new types of OI were added to the Sillence classification, and a new genetic classification consisting of XVIII types is formed. Treatment of patients with OI is a complex task which requires a multidisciplinary care. Pharmacological treatment is based on bisphosphonate treatment, which increases the bone mineral density. In this article, we will describe other approaches in which the effectiveness is studied. Surgical treatment of the fractures and deformities of the extremities showed a positive effect on the patients’ quality of life, despite existing complications. There are a lot of debates about the choice between telescopic and non-telescopic fixators. Rehabilitation plays huge role in the recovery process after fracture and surgeries. Osteogenesis imperfecta (OI) is a heritable bone dysplasia characterized by bone fragility and long bone deformities. Approximately 85% of OI cases are caused by dominant autosomal mutations in the type I collagen coding genes (COL1A1 and COL1A2), which affect the quantity or structure of collagen. The remaining percentage of cases is caused by mutation in the proteins responsible for posttranslational modification, processing and crosslinking of collagen, bone mineralization, and osteoblast differentiation. In the past decade, new recessive, dominant, and X-linked inheritance. As a result, new types of OI were added to the Sillence classification, and a new genetic classification consisting of XVIII types is formed. Treatment of patients with OI is a complex task which requires a multidisciplinary care. Pharmacological treatment is based on bisphosphonate treatment, which increases the bone mineral density. In this article, we will describe other approaches in which the effectiveness is studied. Surgical treatment of the fractures and deformities of the extremities showed a positive effect on the patients’ quality of life, despite existing complications. There are a lot of debates about the choice between telescopic and non-telescopic fixators. Rehabilitation plays huge role in the recovery process after fracture and surgeries.

One of the main problems of modern surgery is treatment of trophic skin and soft tissues defects due to the ambiguity of the pathogenesis, tendency to recurrence, deterioration in the patients’ quality of life, complexity and duration of treatment, large economic costs of treatment and rehabilitation. The article describes an algorithm for outpatient treatment of patients with trophic skin and soft tissues defects in diabetic foot syndrome. Debridement the wound from necrosis, purulent-fibrinous pellicles, wound biofilms is produced by a chemical necrectomy. A method of closing the wound defects by the means of high-tech biomaterials based on collagen type 1 is described.

Background The aim of this study was the investigation of the osteogenic potential of human osteoblasts of advanced donor age in 2D and 3D culture. Methods Osteoblasts were induced to osteogenic differentiation and cultivated, using the same polystyrene material in 2D and 3D culture for 2 weeks. Samples were taken to evaluate alkaline phosphatase (ALP) activity, mineralization and gene expression. Results Osteoprotegerin (OPG) levels were significantly increased (8.2-fold) on day 7 in 3D compared to day 0 (p p p = 0.009). Osteopontin (OP) expression showed 6.5-fold higher levels on day 7 (p = 0.002) in 3D than in 2D. Mineralization was significantly higher in 3D on day 14 (p = 0.0002). Conclusion Advanced donor age human primary osteoblasts reveal significantly higher gene expression levels of OPG, Col1 and OP in 3D than in monolayer. Therefore, it seems that a relatively high potential of bone formation in a natural 3D arrangement is presumably still present in osteoblasts of elderly people. Trial registration 5217/11 on the 22nd of Dec. 2011.

Background Bisphosphonates are the most common treatment for osteoporosis with confirmed efficacy. However, less information is available on prolonged use. This study was performed to examine the risk of osteoporotic vertebral fractures during bisphosphonates holiday and estimate its predictors. Results Forty-two patients completed 2-year fracture-free holiday; 7 had spontaneous vertebral fracture. Among baseline characteristics, age was significantly higher in fracture group (69.99 ± 3.62 vs. 75.37 ± 3.81; P value 0.007); other factors were comparable. Longitudinal changes analysis showed that only alkaline phosphatase (ALP) increment had significant group over time interaction (P value 0.002). The difference between baseline and clinical end-point serum collagen type 1 cross-linked C-telopeptid (CTX) was significant in both fracture and non-fracture groups, whereas femoral neck and total hip BMD decline was significant in fracture group only. Multivariate analysis showed that only age (OR, 1.43; p, 0.011) and history of previous fractures (OR, 13.59; p, 0.044) are significant predictors of vertebral fractures. Conclusions These results suggest that older age and history of previous fracture should be considered as risk factors for vertebral fractures during bisphosphonates holiday. Furthermore, femoral neck and total hip BMD decline could be related to vertebral fractures. By the same token, overt increase of ALP and CTX could be an indicator of fracture occurrence.

Dyslipidemias can affect molecular networks underlying the metabolic homeostasis and vascular function leading to atherogenesis at early stages of development. Since disease-related proteins often interact with each other in functional modules, many advanced network-oriented algorithms were applied to patient-derived big data to identify the complex gene-environment interactions underlying the early pathophysiology of dyslipidemias and atherosclerosis. Both the proprotein convertase subtilisin/kexin type 7 (PCSK7) and collagen type 1 alpha 1 chain (COL1A1) genes arose from the application of TFfit and WGCNA algorithms, respectively, as potential useful therapeutic targets in prevention of dyslipidemias. Moreover, the Seed Connector algorithm (SCA) algorithm suggested a putative role of the neuropilin-1 (NRP1) protein as drug target, whereas a regression network analysis reported that niacin may provide benefits in mixed dyslipidemias. Dyslipidemias are highly heterogeneous at the clinical level; thus, it would be helpful to overcome traditional evidence-based paradigm toward a personalized risk assessment and therapy. Network Medicine uses omics data, artificial intelligence (AI), imaging tools, and clinical information to design personalized therapy of dyslipidemias and atherosclerosis. Recently, a novel non-invasive AI-derived biomarker, named Fat Attenuation Index (FAI™) has been established to early detect clinical signs of atherosclerosis. Moreover, an integrated AI-radiomics approach can detect fibrosis and microvascular remodeling improving the customized risk assessment. Here, we offer a network-based roadmap ranging from novel molecular pathways to digital therapeutics which can improve personalized therapy of dyslipidemias.

Resumo Fundamento A obesidade é um fator de risco para complicações médicas, incluindo o sistema cardiovascular. Há informações limitadas sobre o colágeno no coração obeso. Nosso estudo anterior demonstrou uma redução dos níveis proteicos de colágeno miocárdico tipo I em ratos obesos alimentados com uma dieta com alto teor de gordura durante 34 semanas. No entanto, os mecanismos responsáveis pelos níveis baixos não estão completamente elucidados. Objetivo O objetivo deste estudo foi testar a hipótese de que a redução do colágeno tipo I está associada ao aumento da atividade da metaloproteinase-2 (MMP-2), a qual está ligada à elevação de leptina no miocárdio de ratos obesos. Métodos Ratos Wistar machos com 30 dias de idade foram randomizados em dois grupos: controle (dieta padrão) e obeso (dieta com alto teor de gordura), e alimentados durante 34 semanas. Foram avaliados as características gerais dos animais e os perfis metabólicos e endócrinos. Foram avaliados as expressões proteicas miocárdicas de colágeno tipo I, leptina e inibidores teciduais de metaloproteinases (TIMP), bem como a atividade da MMP-2. O teste de correlação de Pearson foi aplicado para determinar as associações entre variáveis. O nível de significância foi de 5%. Resultados Os animais obesos apresentaram índice de adiposidade mais elevado em comparação ao controle. Foram observadas comorbidades como intolerância à glicose, hiperinsulinemia, resistência à insulina, hiperleptinemia e hipertensão nos ratos obesos. A obesidade reduziu o colágeno tipo I, TIMP-1 e TIMP-2, e aumentou a leptina e a MMP-2 no miocárdio. Houve uma correlação negativa entre o colágeno tipo I e a MMP-2 e uma correlação positiva entre a leptina e a MMP-2. Conclusão Foi confirmada a hipótese de que a redução do colágeno tipo I está associada ao aumento da atividade da MMP-2 e da expressão de leptina no miocárdio de ratos obesos. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0) Abstract Background Obesity is a risk factor for medical complications, including the cardiovascular system. There is limited information on collagen in the heart in obesity. Our previous study showed decreased protein levels of myocardial collagen type I in obese rats fed a high-fat diet for 34 weeks. However, the mechanisms responsible for low levels are not fully elucidated. Objective The purpose of this study was to test the hypothesis that the reduction in collagen type I is associated with increased metalloproteinase-2 (MMP-2) activity, which is linked to elevated leptin in the myocardium of obese rats. Methods Thirty-day-old male Wistar rats were randomized into two groups, control (standard diet) and obese (high-fat diet), and fed for 34 weeks. The general animal characteristics and metabolic and endocrine profiles were evaluated. Myocardial protein expressions of collagen I, leptin, tissue inhibitors of metalloproteinases (TIMP), and MMP-2 activity were assessed. Pearson correlation was employed to determine the associations between variables. The level of significance was 5%. Results The obese animals had increased adiposity index compared to control. Comorbidities such as glucose intolerance, hyperinsulinemia, insulin resistance, hyperleptinemia, and hypertension were observed in obese rats. Obesity reduced collagen I, TIMP-1, and TIMP-2, and it increased leptin and MMP-2 in the myocardium. There was a negative correlation between collagen I and MMP-2 and a positive correlation between leptin and MMP-2. Conclusion The hypothesis was confirmed; the reduction in collagen type I is associated with increased MMP-2 activity and leptin expression in the myocardium of obese rats. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)

Background: On stopping bisphosphonate treatment, bone resorption may increase before evidence of a decrease in bone density. Offset of bisphosphonate effect may therefore be monitored by measuring C-terminal telopeptide (CTX) following long-term bisphosphonate treatment to inform clinical decisions on drug holiday. Methods: Retrospective analysis of 158 patients (83% female, mean age 71 years) starting a drug holiday had plasma CTX measured at discontinuation (baseline), n=138 and 4 months and n=136, and 12 months (n=100). Premenopausal mean CTX levels and the least significant change (LSC) detectable were used to define target thresholds for bone turnover. Results: Following long-term bisphosphonate treatment (69% alendronic acid, 33% risedronate, mean duration 8 years SD 2.7), 32% patients had CTX above target (0.19 μg/L). In those with baseline CTX below threshold, 28% increased CTX to >0.19 μg/L and > LSC (0.06 μg/L) by 4 months (mean CTX increase 0.05 μg/L [95% confidence interval (CI): 0.04–0.06; p

Tideglusib is a glycogen synthase kinase 3 (GSK-3) inhibitor which has shown the effects of bone regeneration, used for the treatment of Alzheimer disease. The aim of the study was to determine the effects of Tideglusib in the apoptosis and the bone regeneration in rats with calvarial defects. Twenty male Wistar rats (aged 11-13 weeks) were used for the study. Full-thickness flap elevated to exposure calvarial bone. Two 5 mm critical size calvarial defects were created on each rat calvarium. The defects were divided into 4 study groups: 1-Control (n = 10); 2- Gelatin sponge+Tideglusib (Gs+TDG; n = 10); 3- Autogenous bone (AB; n = 10); 4-Autogenous bone+Tideglusib (AB+TDG; n = 10). Then, the rats were sacrificed at fourth week. Three-dimensional imaging, histopathologic and immunohistochemical examinations were performed to evaluate the samples. The most increased bone formation and interaction between graft and new bone were observed in AB+TDG group. Bone morphogenic protein-2 (BMP-2), alkaline phosphatase (ALP), collagen type 1 (Col 1) and osteocalcin (OCN) was determined significantly higher in Tideglusib received groups compared with those of Control and AB groups (P < 0.05). Osteoclast numbers found to be higher in Gs+TDG and AB+TDG groups as well as RANKL expression dis not affected in Gs+TDG group but decreased in AB+TDG group comparing those of Control and AB groups. In addition, Tideglusib increased the Bcl-2 levels (P < 0.05) and decreased Bax levels (P > 0.05) in Tideglusib received groups compared with their controls. The administration of Tideglusib in calvarial bone defects increased bone mineral density, new bone area and total bone area by decreasing apoptosis and increasing osteoblastogenesis.

The aim of this study was the investigation and comparison of the presence of vascular endothelial growth factor (VEGF), collagen type 1 and the proteoglycan versican in the discus articularis in relation to dental status (full dentition [1], partial dentition [2] and edentulous [3]). The right disci articulares were removed from 17 donated bodies (6 with full dentition, 5 with partial dentition and 6 edentulous). The specimens were immunohistochemically stained for VEGF, collagen type 1 and versican. Semiquantitative analysis of the disci was conducted within the groups based on the intensity of immunoreactivity of VEGF, collagen type 1 and versican. In addition, a pairwise comparison was carried out between the three experimental groups. The results revealed significantly higher immunoreactivity for VEGF and versican in groups 2 and 3 than in group 1. Conversely, determination of immunoreactivity was significantly higher in group 1 for collagen type 1 than in the other two groups. These results indicate an elevated presence of the proteoglycan versican and the neoangiogenesis factor VEGF when the occlusal supporting zone has been lost. By contrast, detection of collagen type 1 is reduced. The loss of collagen type 1 and rise in versican and VEGF suggest increasing degeneration when the supporting zone is lost due to the loss of teeth.

Biocompatibility takes into account the ability of a material to elicit a specific biological response after administration to a living organism. The concept does not define only one quality of the material, but reflects a complex of interactions with the biological environment in which it is placed. Over time, the definition of biocompatibility has gradually changed. Dental cements are the main clinical obturating materials. First created by Wilson and Kent in 1969, glass ionomer (polyalkenoate) cements have become widely used in medicine and dentistry. The purpose of this review is to discuss the biocompatibility of glass ionomer cements. Scientific databases - PubMed and SCOPUS were used to find appropriate studies in English on the topic of this article, with the following keywords - biocompatibility, glass ionomer cements, dentistry. A time period of 2000-2021 was set to screen articles and track the progress of the biocompatibility of dental cements in the new millennium. In addition to the cited scientific databases and articles such as clinical trials, review articles, meta-analyzes, writing of the report included information from Bulgarian and foreign textbooks in English on the subject. After applying the screening criteria, 61 results were displayed in SCOPUS and 215 in PubMed. From them, selected articles that describe experimental productions with testing the properties of cements, incl. to living cells, were reviewed. Science has found that by modifying the composition of the powder and the liquid of the cement, properties and biocompatibility can be affected. Modifications with the addition of nanoparticles hydroxylapatite and silica, carbon nanocompounds, zinc ions, cellulose microfiber and nanocrystals, amorphous calcium phosphate, chlorhexidine, collagen type 1 and peptides have been reported. Cement liquid has also been improved, which changes its properties. In the given time period between 2000-2021 there is a rapid rise of development and improvement of the properties of already synthesized cements. Efforts are being made to study the biocompatibility of materials and their properties to help tissue regeneration. There is also a wider use of materials and their implementation into various fields of medicine and dentistry.

Background: Orthodontics of the 21st century requires aesthetic, painless, predictable, and quick treatments. This demand for faster results generated orthodontic movement acceleration pro...

Made available in DSpace on 2020-12-10T19:50:40Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-02-15 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) The reconstructive techniques have been widely used in Veterinary Medicine. The post-operative adjuvants therapies like the low-level laser therapy (LLLT) are used to decrease inherent complications to reconstructive surgeries. This article purposed to define the LLLT effects on the healing, inflammation, and vascularization of the skin grafts in applicable time intervals to veterinary surgical routine. Forty rats (Rattus norvegicus albinus wistar) were used and each one was submitted to autogenous cutaneous mesh grafting in the interescapular region. The rats were randomly distributed in five groups (G1, G2, G3, G4, and G5) in accordance with the 6 J/cm(2) or 10 J/cm(2) dose every 3 or 5 days. These treatments were applied on the skin graft for 15 days. The histochemical evaluation with Picrosirius showed greater expression of collagen type 1 - red in grafts of G5 (p < 0.05), while in G1 did not; the expression of collagen type III - green was not induced by LLLT. The histochemical evaluation with hematoxylin-eosin showed greater numbers of fibroblasts in grafts of G4 (p < 0.05) and less hemorrhage in grafts of G5 (p < 0.05). There was modulation of the inflammatory response in irradiated skin grafts. It is concluded the exhibition of the skin grafts to 6 J/cm(2) or 10 J/cm(2) dose every 5 days improved the healing and the modulation of the local inflammation. Univ Estadual Paulista, Dept Clin & Cirurgia Vet, Jaboticabal, SP, Brazil Univ Estadual Paulista, Dept Clin & Cirurgia Vet, Fac Ciencias Agr & Vet, Via Acesso Prof Paulo Donato Castellane S-N, BR-14884900 Jaboticabal, SP, Brazil Hosp Canc Barretos, Ctr Pesquisa Oncol Mol, Barretos, SP, Brazil Univ Estadual Paulista, Dept Clin & Cirurgia Vet, Jaboticabal, SP, Brazil Univ Estadual Paulista, Dept Clin & Cirurgia Vet, Fac Ciencias Agr & Vet, Via Acesso Prof Paulo Donato Castellane S-N, BR-14884900 Jaboticabal, SP, Brazil FAPESP: 2017/25951-9

Background: Hypertension causes cardiac hypertrophy, cardiac dysfunction and heart failure (HF). Despite the importance of cardiac hypertrophy as an independent risk factor for the development of HF, not all hypertrophied hearts will ultimately fail. Alterations in the extracellular matrix have also been shown to contribute to this process. This study aimed to investigate whether alterations in the levels of profibrotic proteins contribute to the transition of compensated cardiac hypertrophy to HF. Methods: Male rats were subjected to abdominal aorta constriction. After 90 days post surgery (dps), the hearts were collected and Western blot was performed to collagens type I and III, MMP-14, MMP-2, TIMP-2, Integrin and TGF-β. The interstitial collagen area was quantified. Cardiac function was evaluated using the Vevo 2100 ultrasound. Data were considered significant when p Results: At 90 dps, 75% (30 of 40) presented hypertrophic hearts (HH) and 25% (10 of 40) hypertrophic+dilated hearts (HD) in the echocardiography. In addition, systolic (ejection fraction: 33.5%±1.3; fractional shortening: 21.90±4.3%) and diastolic functions (mitral E-wave velocity: 1279±127 mm/s and E/E' ratio: 68.14±16.78) were importantly reduced in the HD group when compared to HH. Although the interstitial collagen content in the left ventricle was not different between HH (3.63±0.40%) and HD (3.75±0.39%) groups, the amount of type III collagen increased (1.28±0.34 AU) while type I collagen showed significant reduction (0.76±0.16 AU) in the HD group when compared to HH (0.90±0.26 AU and 1.11±0.11 AU, respectively). Important increases were seen in the protein levels of TGF-B, integrin, MMP-14, MMP-2 and TIMP-2 in the HD and HH groups when compared to sham, but there is no difference between HD and HH groups. Conclusion: Although there is significant fibrosis in the hearts of animals after 90 dps, the imbalance between type I and III collagens associated with systolic and diastolic function could contribute to the transition to decompensated hypertrophy in this experimental model of cardiac hypertrophy.

BackgroundPosterior capsule opacification (PCO) after cataract surgery is influenced by intraocular lens (IOL) design and material. The following is an ex vivo comparison of PCO between the Clareon vs. the AcrySof IOL in human capsular bags.MethodsTwenty cadaver capsular bags from 10 human donors were used, with the novel hydrophobic IOL (Clareon, CNA0T0) being implanted in one eye and the other eye of the same donor receiving the AcrySof IOL (SN60WF) following phacoemulsification cataract surgery. Five capsular bags of 3 donors served as controls without IOL. Cellular growth of lens epithelial cells was photo-documented daily. The primary endpoint was the time until full coverage of the posterior capsule by cells. Furthermore, immunofluorescence staining of capsular bags for the fibrotic markers f-actin, fibronectin, alpha smooth muscle actin, and collagen type 1 were performed.ResultsThe new Clareon IOL did not show any disadvantages in terms of days until full cell coverage of the posterior capsule in comparison to the AcrySof (p > 0.99). Both, the Clareon (p = 0.01, 14.8 days) and the AcrySof IOL (p = 0.005, 15.7 days) showed a slower PCO development in comparison to the control (8.6 days). The fibrotic markers f-actin, fibronectin, alpha smooth muscle actin, and collagen type 1 were equally distributed between the two IOLs and differed from the control.ConclusionsA comparable performance has been found in the ex vivo formation of PCO between the two IOLs. Long-term clinical studies are necessary to reach final conclusions.

Background: The action of bone cells on the bone mineral density can be highlighted from their enzymatic activities, by the bone alkaline phosphates (BAP) and the Cross Laps-telopeptide terminal of the collagen type 1 (β-CTX). They are reliable to explore the activity of bone turnover. We aim to put in perspective the association between gynecological factors and the concentration of bone turnover markers (BTMs) among Moroccan women. Methods: This is a cross-sectional study of 125 women from February to April 2015. A randomized sample was made. The biochemical parameters of bone metabolism concerned serum calcium, 25 hydroxyvitamin D (25OHD), parathyroid hormone (PTH), phosphorus , BAP and β-CTX. All data related to gynecologic, sociodemographic and anamnesis parameters was collected by standardized questionnaire. Result: Among 125 women, 64(51.42) were menopausal, the mean BAP was 22.1±7.6 ng/L, the median of the interval between successive births “IBSB” and of β-CTX were 36.0[24.0-58.0] months, 368.5 [237.0-504.8]ng/L. A positive correlation was observed between the β-CTX and IBSB (r=0.2,p=0.05). The BAP concentration was higher in menopausal women (p

The role of fibrocytes in chronic obstructive pulmonary disease (COPD) is unknown. We sought to enumerate blood and tissue fibrocytes in COPD and determine the association of blood fibrocytes with clinical features of disease.Utilizing flow cytometry to identify circulating, collagen type 1Blood and tissue fibrocytes were not increased compared to control subjects nor were blood fibrocytes associated with lung function or qCT, but were increased in eosinophilic COPD. Myeloid-derived suppressor cell-like fibrocytes were increased in COPD compared to controls [2.3 (1.1-4.9), P = 0.038]. Our path analysis model showed that collagen type 1 intensity for MDSC-like fibrocytes was positively associated with lung function through associations with air trapping, predominately in the upper lobes.We have demonstrated that two circulating populations of fibrocyte exist in COPD, with distinct clinical associations, but are not prevalent in proximal or small airway tissue. Blood MDSC-like fibrocytes, however, are increased and associated with preserved lung function through a small airway-dependent mechanism in COPD.

// Stephanie Blockhuys 1, 3 , Na Liu 1 , Nisha Rani Agarwal 3 , Annika Enejder 3 , Vesa Loitto 2 , Xiao-Feng Sun 1 1 Department of Oncology and Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden 2 Medical Microbiology, Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden 3 Molecular Microscopy, Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden Correspondence to: Xiao-Feng Sun, email: xiao-feng.sun@liu.se Stephanie Blockhuys, email: steblo@chalmers.se Keywords: collagen type 1, colorectal cancer, X-radiation, cell migration, integrin β1 Received: March 17, 2016 Accepted: September 13, 2016 Published: September 19, 2016 ABSTRACT Rectal cancer treatment still fails with local and distant relapses of the disease. It is hypothesized that radiotherapy could stimulate cancer cell dissemination and metastasis. In this study, we evaluated the effect of X-radiation on collagen type I strap formation potential, i.e. matrix remodeling associated with mesenchymal cell migration, and behaviors of SW480, SW620, HCT116 p53 +/+ and HCT116 p53 −/− colon cancer cells. We determined a radiation-induced increase in collagen type I strap formation and migration potentials of SW480 and HCT116 p53 +/+ . Further studies with HCT116 p53 +/+ , indicated that after X-radiation strap forming cells have an increased motility. More, we detected a decrease in adhesion potential and mature integrin β1 expression, but no change in non-muscle myosin II expression for HCT116 p53 +/+ after X-radiation. Integrin β1 neutralization resulted in a decreased cell adhesion and collagen type I strap formation in both sham and X-radiated conditions. Our study indicates collagen type I strap formation as a potential mechanism of colon cancer cells with increased migration potential after X-radiation, and suggests that other molecules than integrin β1 and non-muscle myosin II are responsible for the radiation-induced collagen type I strap formation potential of colon cancer cells. This work encourages further molecular investigation of radiation-induced migration to improve rectal cancer treatment outcome.

To determine how collagen production by tympanic membrane fibroblasts is affected by ciprofloxacin at levels found in eardrops.Prospective, controlled, and blinded cell culture study.Academic tertiary medical center.Cell culture of mouse fibroblasts.A primary fibroblast culture was established from mouse tympanic membranes. Fibroblasts were cultured until they were 75% confluent, then treated with dilute hydrochloric acid (control) or ciprofloxacin (0.01% or 0.3%) for 24 or 72 hours for Western blotting and for 24 or 48 hours for cytotoxicity assay. Cells were observed with phase-contrast microscope. Western blotting was performed for collagen type 1 α1 (collagen 1A1) and α-tubulin.Fibroblasts treated with 0.01% and 0.3% ciprofloxacin for 24 hours had lower levels of collagen 1A1 (P = .0005 and P.0001, respectively) and α-tubulin (both P.0001) than control fibroblasts. Collagen 1A1 and α-tubulin levels were lower in fibroblasts treated with 0.3% than with 0.01% ciprofloxacin (P = .02 and P = .014). After 72 hours, 0.3% ciprofloxacin completely eliminated collagen 1A1 and α-tubulin (P.001). Cells treated with 0.01% ciprofloxacin for 72 hours also had lower collagen 1A1 (P.0001) and α-tubulin (P = .005) as compared with the control. Seventy-two-hour incubation in 0.01% or 0.3% ciprofloxacin resulted in lower levels of collagen 1A1 (P = .009 and P.0001, respectively) and α-tubulin (P = .007 and P.0001, respectively) than 24-hour incubation. Cytotoxicity assay and phase-contrast microscopy mirrored these findings.Treatment of tympanic membrane fibroblasts with 0.3% ciprofloxacin, as found in eardrops, reduces fibroblast viability and collagen and α-tubulin protein levels. These findings could explain tympanic membrane healing problems associated with quinolone eardrops.

Increased tendon stiffness in response to mechanical loading is well established in young animals. Given that tendons stiffen with aging, we aimed to determine the effect of increased loading on tendons of old animals. We subjected 28-month-old mice to 10 weeks of uphill treadmill running; sedentary 8- and 28-month-old mice served as controls. Following training, plantaris tendon stiffness and modulus were reduced by approximately half, such that the values were not different from those of tendons from adult sedentary animals. The decrease in plantaris tendon stiffness was accompanied by a similar reduction in the levels of advanced glycation end-product protein adducts in tibialis anterior tendons of trained compared with sedentary old mice. In Achilles tendons, elevated mRNA levels for collagen type 1, matrix-metalloproteinase-8, and lysyl oxidase following training suggest that collagen turnover was likely also increased. The dramatic mechanical and structural changes induced by training occurred independent of changes in cell density or tendon morphology. Finally, Achilles tendon calcification was significantly reduced following exercise. These results demonstrate that, in response to exercise, tendons from old animals are capable of replacing damaged and dysfunctional components of extracellular matrix with tissue that is mechanically and structurally comparable to adult tissue.

demir ÖMA, Tancer-Elçi H, Polat A, Güçtürk İ, Tepeli E, Zeybek S, Ayaz A. Familial mutation in Caffey disease with reduced penetrance: A case report. Turk J Pediatr 2016; 58: 650-653.Caffey disease is a rare condition of early infancy, characterized by soft tissue swelling, bone lesions, and hyperirritability. Its typical radiological finding is periosteal new bone formation. It can be sporadic or inherited in an autosomal dominant manner. There is no specific treatment. In symptomatic cases, non-steroidal anti-inflammatory drugs such as ibuprofen, indomethacin, or naproxen can be used. This is a report of an infant who presented with restlessness, irritability, and swelling over his shins, diagnosed as Caffey disease. Although there was no family history, the genetic analysis revealed heterozygous missense mutation (c.3040C>T) in type-I-collagen-alpha-1-chain gene in the patient in addition to his mother, grandmother, aunt, and cousin. After indomethacin therapy, the complaints of the patient were completely resolved and his bone lesions were significantly improved. This case report is a familial form of Caffey disease from Turkey, with proven heterozygous mutation in the patient and the family members

Introduction: Gold sea cucumber (Stichopus hermanii) is a marine organism that contains omega-3 and glycosaminoglycan for enhancing collagen needed in the healing process. This study was aimed to determine the effectiveness of gold sea cucumber extracts in accelerating the healing process of oral traumatic ulcer in Wistar rats, in terms of the correlation between collagen type I expression, ulcer diameter, and body weight loss. Methods: Twenty Wistar rats (Rattus norvegicus) was divided into four groups and treated with gold sea cucumber extracts with the concentration of 80%, 40%, and 20% in the form of 0.1 ml gel daily. The negative control group received no treatment. Ulceration of the lower lip of labial mucosa was induced by a burnisher. The animals were observed for 7 days, during which they were weighed and the ulcers diameter was measured. The rats were then sacrificed after 7 days of treatment. Histometric analysis of collagen type I expression was also performed. Data obtained were analysed for differences between the group with one-way ANOVA test and the correlation was analysed with the Pearson test. Results: The significant differences (p < 0.05) between treatment groups was found in the ulcer diameters and the collagen type I expression. The most decreased ulcer diameter and the highest collagen type I expression detected in the group of treatment with a concentration of 80% — no significant differences found in the weight loss between-groups (p > 0.05). Strong correlation was also found between the expression of collagen type I and diameter of ulcer (Pearson correlation = 0.599, p = 0.05), however, no correlation found between weight loss with the expression of collagen type I (Pearson correlation = -0.102, p = 0.66), and the ulcer diameter (Pearson correlation = 0.022, p = 0.92). Conclusion: Gold sea cucumber had a potential benefit to be used as a traumatic ulcer healing medicament. Water extract of gold sea cucumber able to accelerate traumatic ulcer healing by enhancing the production of collagen type I and reduce the diameter of ulcer. There is a strong correlation between collagen type 1 expression and diameter of ulcer, and a weak correlation found between body weight loss and collagen type I expression, also with reducing ulcer diameter.Keywords: Gold sea cucumber, Stichopus hermanii, healing process, traumatic ulcer.

Low birth weight is associated with reduced bone mass and density in adult life. However, effects of maternal hypoxia (MH) on offspring bone development are not known.Objective. The current study investigated the effects of fetal growth restriction induced by MH during the last half of gestation on bone structure and volume in the offspring of the fetus near term and the pup in adolescence.Methods. During 35–62-day gestation (term, 69d), guinea pigs were housed in room air (21% O2; control) or 12% O2(MH). Offspring femur and tibia were collected at 62d gestation and 120d after birth.Results. MH decreased fetal birth weight but did not affect osteogenic potential pools in the fetal bone marrow. Histological analysis showed no effects of MH on tibial growth plate thickness in either fetal or postnatal offspring, although there was increased VEGF mRNA expression in the growth plate of postnatal offspring. MH did not change primary spongiosa height but lowered collagen-1 mRNA expression in postnatal offspring. There was increased mRNA expression of adipogenesis-related gene (FABP4) in bone from the MH postnatal offspring.Conclusion. MH during late gestation did not change the pool of osteogenic cells before birth or growth plate heights before and after birth. However, MH reduced expression of bone formation marker (collagen-1) and increased expression of fat formation marker (FABP4) in postnatal offspring bone.

There is an urgent need for more efficient treatment of chronic wounds in diabetic patients especially with a high risk of leg amputation. Biomaterials capable of presenting extracellular matrix-mimetic signals may assist in the recovery of diabetic wounds by creating a more conducive environment for blood vessel formation and modulating the immune system. In a previous study, we showed that glycosaminoglycan-mimetic peptide nanofibers are able to increase the rate of closure in STZ-induced diabetic rats by induction of angiogenesis. The present study investigates the effect of a heparin-mimetic peptide amphiphile (PA) nanofiber gel on full-thickness excisional wounds in a db/db diabetic mouse model, with emphasis on the ability of the PA nanofiber network to regulate angiogenesis and the expression of pro-inflammatory cytokines. Here, we showed that the heparin-mimetic PA gel can support tissue neovascularization, enhance the deposition of collagen and expression of alpha-smooth muscle actin (α-SMA), and eliminate the sustained presence of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in the diabetic wound site. As the absence of neovascularization and overexpression of pro-inflammatory markers are a hallmark of diabetes and interfere with wound recovery by preventing the healing process, the heparin-mimetic PA treatment is a promising candidate for acceleration of diabetic wound healing by modulating angiogenesis and local immune response. © 2017 The Royal Society of Chemistry.

// Christiana Polydorou 1, * , Fotios Mpekris 1, * , Panagiotis Papageorgis 1, 2 , Chrysovalantis Voutouri 1 , Triantafyllos Stylianopoulos 1 1 Cancer Biophysics Laboratory, Department of Mechanical and Manufacturing Engineering, University of Cyprus, Nicosia, Cyprus 2 Department of Life Sciences, Program in Biological Sciences, European University Cyprus, Nicosia, Cyprus * These authors contributed equally to this work Correspondence to: Triantafyllos Stylianopoulos, email: tstylian@ucy.ac.cy Keywords: tumor perfusion, vessel compression, breast cancer, drug delivery, biomechanics Received: December 06, 2016 Accepted: February 12, 2017 Published: February 20, 2017 ABSTRACT Normalization of the tumor microenvironment by selectively targeting components of the tumor extracellular matrix has been recently proposed to have the potential to decompress tumor blood vessels, increase vessel perfusion and thus, improve drug delivery and the efficacy of cancer therapy. Therefore, we now need to identify safe and well tolerated pharmaceutical agents that are able to remodel the microenvironment of solid tumors and enhance chemotherapy. In this study, we repurposed Pirfenidone, a clinically approved anti-fibrotic drug for the treatment of idiopathic pulmonary fibrosis, to investigate its possible role on tumor microenvironment normalization. Using two orthotopic mammary tumor models we demonstrate that Pirfenidone reduces collagen and hyaluronan levels and, as a result, significantly increases blood vessel functionality and perfusion and improves the anti-tumor efficacy of doxorubicin. Reduction of extracellular matrix components were mediated via TGFβ signaling pathway inhibition due to downregulation of TGFβ1, COL1A1, COL3A1, HAS2, HAS3 expression levels. Our findings provide evidence that repurposing Pirfenidone could be used as a promising strategy to enhance drug delivery to solid tumors by normalizing the tumor microenvironment.

Osteogenesis imperfecta (OI) is characterized by a high fracture rate and great heterogeneity. This cross-sectional study presents skeletal investigations and protein analyses in 85 adult OI patients. We find significant differences in bone mass, architecture, and fracture rate that correlate well with the underlying biochemical and molecular abnormalities.INTRODUCTION: OI is a hereditary disease characterized by compromised connective tissue predominantly caused by mutations in collagen type 1 (COL-1) encoding genes. Widespread symptoms reflect the ubiquity of COL-1 throughout the body. The purpose of this study was to improve our understanding of clinical manifestations by investigating anthropometry and skeletal phenotypes (DXA, HRpQCT) in an adult OI population and compare the findings to underlying COL-1 genotype and structure.METHODS: The study comprised 85 OI patients aged 45 (19-78) years, Sillence type I (n = 58), III (n = 12), and IV (n = 15). All patients underwent DXA, HRpQCT, spine X-ray, biochemical testing, and anthropometry. COL1A1 and COL1A2 were sequenced and 68 OI causing mutations identified (46 in COL1A1, 22 in COL1A2). Analysis of COL-1 structure (quantitative/qualitative defect) by SDS-PAGE was performed in a subset (n = 67).RESULTS: A qualitative collagen defect predisposed to a more severe phenotype with reduced aBMD, more fractures, and affected anthropometry compared to patients with a quantitative COL-1 defect (p < 0.05). HRpQCT revealed significant differences between patients with OI type I and IV. Patients with type I had lower vBMD (p < 0.005), thinner cortexes (p < 0.001), and reduced trabecular number (p < 0.005) compared to patients with type IV indicating that HRpQCT may distinguish type I from type IV better than DXA.CONCLUSION: The defective collagen in patients with OI has pronounced effects on the skeleton. The classical OI types based on the clinical classification show profound differences in bone mass and architecture and the differences correlate well with the underlying biochemical and molecular collagen abnormalities.

Objective Bone changes are increasingly described after burn. How bone markers could help to detect early bone changes or to screen burn patients at higher risk of demineralization is still not made clear. We performed an observational study assessing the changes in serum bone markers after moderate burn. Methods Adults admitted in the first 24 h following burn extended on >10% body surface area were included. Serum levels of collagen type 1 cross-linked C-telopeptide (CTX), tartrate-resistant acid phosphatase 5b (TRAP), type 1 procollagen N-terminal (P1NP) and bone alkaline phosphatase (b-ALP) were measured at admission and every week during the first month. Data are expressed as median [min-max]. Results Bone markers were measured in 20 patients: 18 men, 2 women (including one post-menopausal). Age was 46 [19–86] years old, burn surface area reached 15 [7–85] %. Twelve patients completed the study. All biomarkers mainly remained into normal ranges during evolution. A huge variability was observed regarding biomarkers evolution. Patient's evolution was not linear and could fluctuate from a decrease to an increase of blood concentrations. There was not necessarily a consistency between the two formation or the two resorption markers. Variations observed between two consecutive measurements were lesser than the accepted critical difference in almost one third of the cases. Conclusions Considering available data, role and interest of bone markers in management of burn related bone disease remain unclear.

Objective: To evaluate the evolution of injuries of the supraspinatus muscle by immunohistochemistry (IHC) and anatomopathological analysis in animal model (Wistar rats). Methods: Twenty-five Wistar rats were submitted to complete injury of the supraspinatus tendon, then subsequently sacrificed in groups of five animals at the following periods: immediately after the injury, 24h after the injury, 48h after, 30 days after and three months after the injury. All groups underwent histological and IHC analysis. Results: Regarding vascular proliferation and inflammatory infiltrate, we found a statistically significant difference between groups 1(control group) and 2 (24h after injury). IHC analysis showed that expression of vascular endothelial growth factor (VEGF) showed a statistically significant difference between groups 1 and 2, and collagen type 1 (Col-1) evaluation presented a statistically significant difference between groups 1 and 4. Conclusion: We observed changes in the extracellular matrix components compatible with remodeling and healing. Remodeling is more intense 24h after injury. However, VEGF and Col-1 are substantially increased at 24h and 30 days after the injury, respectively. Level of Evidence I, Experimental Study.

The interaction of dietary and genetic factors may affect the development of bone deterioration. This study investigated whether the effects of dietary acid load (DAL) on bone loss in postmenopausal Chinese women were moderated by the insulin-like growth factor-1 (IGF-1) single nucleotide polymorphism, a known gene that plays a role in the regulation of bone formation and bone remodeling. A total of 217 healthy participants were recruited from the National Council of Senior Citizens Organizations Malaysia. Serum collagen type 1 cross-linked C-telopeptide was used as a surrogate bone marker to assess bone resorption and Agena&reg, MassARRAY genotyping analysis was used to identify the signaling of IGF-1 rs35767. The dietary acid load was measured by potential renal acid load score while physical activity was ascertained using the Global Physical Activity Questionnaire. Hierarchical regression was applied to test the main and interaction effects of DAL and IGF-1 genotypes in bone resorption. The result supported the diet-dependent acid-base balance theory that higher DAL was positively associated with bone resorption (&beta, = 0.152, p = 0.031, F(6,207) = 2.11, sig-F = 0.036, R2 = 0.079). However, the results indicated that there was no significant correlation between IGF-1 and bone resorption, or any significant interaction between DAL and IGF-1. In conclusion, there was no moderating effect of IGF-1 on the relationship between DAL and bone resorption.

Context: Molecules that are released into biological fluids during matrix metabolism of articular cartilage, subchondral bone, and synovial tissue could serve as biochemical markers of the process of osteoarthritis (OA). Unfortunately, actual breakthroughs in the biochemical OA marker field are limited so far. Objective: By reviewing the status of commercially available biochemical OA markers according to the "Burden of disease, Investigative, Prognostic, Efficacy of intervention, and Diagnostic" ("BIPED") classification, future use of this "BIPED" classification is encouraged and more efficient biochemical OA marker research stimulated. Data sources: Three electronic databases [PubMed, Scopus, EMBASE (1997-May 2009)] were searched for publications on blood and urinary biochemical markers in human primary knee and hip-OA. Study selection: Stepwise selection of original English publications describing human studies on blood or urinary biochemical markers in primary knee or hip-OA was performed. Selected articles were fully read to determine whether biochemical markers were investigated on performance within any of the "BIPED" categories. Eighty-four relevant publications were identified. Data extraction: Data from relevant publications were tabulated according to the "BIPED" classification. Individual analyses within a publication were summarized in general "BIPED" scores. Data synthesis: An uneven distribution of scores on biochemical marker performance and heterogeneity among the publications complicated direct comparison of individual biochemical markers. Comparison of categories of biochemical markers was therefore performed instead. In general, biochemical markers of cartilage degradation were investigated most extensively and performed well in comparison with other categories of biochemical markers. Biochemical markers of bone metabolism performed less adequately. Biochemical markers of synovial tissue metabolism were not investigated extensively, but performed quite well. Conclusions: Specific biochemical markers and categories of biochemical markers as well as their nature, origin and metabolism, need further investigation. International standardization of future investigations should be pursued to obtain more high-quality, homogenous data on the full spectrum of biochemical OA markers. © 2010 Osteoarthritis Research Society International.

The objective of the present study was to test the hypothesis that the fracture strength of calcium hydroxide and mineral trioxide aggregate (MTA)-filled immature teeth decreased over time. Immature mandibular incisors from sheep were extracted and the pulps were extirpated using an apical approach with a barbed broach, and the teeth were divided into three experimental groups. Group 1: untreated teeth. Group 2: the root canals were filled with calcium hydroxide paste. Group 3: the root canals were filled with MTA. All specimens were kept in saline with 1% antibiotics at 4 degrees C for certain periods of time: 2 weeks, 2 months, and 1 year. Then they were tested for fracture strength in an Instron testing machine. The results were subjected to statistical analysis by the Tukey-Kramer tests. A P-value (0.05) was considered statistically significant. One tooth from each group was selected randomly for a histological study, examining matrix metalloproteinases (MMP2 and MMP14) and tissue inhibitor of metalloproteinase (TIMP). The results showed the mean fracture strengths decreased over time for all the three groups. Although the untreated teeth showed the highest value (45.5 MPa) at 2 weeks, the fracture strengths decreased significantly after 2 months (P0.05). On the other hand, the teeth treated with calcium hydroxide or MTA decreased, but not significantly over time (P0.05). For the MTA-treated teeth, the fracture strengths were not found significantly different from the untreated or calcium hydroxide-treated teeth at 2 weeks or 2 months (P0.05). However, the strength was significantly higher in the MTA group compared with the other two groups after 1 year (P0.05). Immunofluorescence images revealed expression of collagen type 1, MMP-2 and MMP-14 in both untreated and endodontically treated teeth. However, TIMP-2 was only observed in the MTA-treated teeth. In conclusion, the teeth with root treatment with MTA showed the highest fracture resistance at 1 year (P0.05). An explanation could be that MTA induced the expression of TIMP-2 in the dentin matrix and thereby possibly prevented destruction of the collagen matrix.

Item does not contain fulltext PURPOSE: A readily available artificial urinary conduit might be substituted for autologous bowel in standard urinary diversions and minimize bowel associated complications. However, the use of large constructs remains challenging as host cellular ingrowth and/or vascularization is limited. We investigated large, reinforced, collagen based tubular constructs in a urinary diversion porcine model and compared subcutaneously pre-implanted constructs to cell seeded and basic constructs. MATERIALS AND METHODS: Reinforced tubular constructs were prepared from type I collagen and biodegradable Vicryl(R) meshes through standard freezing, lyophilization and cross-linking techniques. Artificial urinary conduits were created in 17 female Landrace pigs, including 7 with a basic untreated construct, 5 with a construct seeded with autologous urothelial and smooth muscle cells, and 5 with a free graft formed by subcutaneous pre-implantation of a basic construct. All pigs were evaluated after 1 month. RESULTS: The survival rate was 94%. At evaluation 1 basic and 1 cell seeded conduit were occluded. Urinary flow was maintained in all conduits created with pre-implanted constructs. Pre-implantation of the basic construct resulted in a vascularized tissue tube, which could be used as a free graft to create an artificial conduit. The outcome was favorable compared to that of the other conduits. Urinary drainage was better, hydroureteronephrosis was limited and tissue regeneration was improved. CONCLUSIONS: Subcutaneous pre-implantation of a basic reinforced tubular construct resulted in a vascularized autologous tube, which may potentially replace bowel in standard urinary diversions. To our knowledge we introduce a straightforward 2-step procedure to create artificial urinary conduits in a large animal model.

Osteogenesis imperfect (OI) is a rare genetic disease, caused by generalized defect in collagen type 1. Clinical forms of the disease vary from mild (OI type I) or moderate (OI type IV -VII) to severe features (OI type II and III). It is caused by genetic defects in the synthesis of type 1 collagen. About 90% of the cases are due to mutations in COL1A1 and COL1A2.The incidence is 1/20.000 birth [1-8].

Fibrosis is a common endpoint of a multiplicity of chronic diseases resulting in scarring and loss of organ function. To improve and accelerate antifibrotic drug discovery, there is an urgent need for reliable and reproducible human in vitro methods that also include the cellular diversity that epitomize specific organs. The objective of our study was to investigate fibrogenesis in precision-cut tissue slices (PCTS) from human liver and kidney. Moreover, we strove to elucidate the effect of imatinib - a promising antifibrotic compound in rat - in the early stages of liver fibrosis. PCTS were successfully prepared from human livers and kidneys, and cultured up to 72 hours. Viability of PCTS was assessed by the ATP content of the slices. Furthermore, gene expression of several fibrosis markers was determined. The antifibrotic effect of imatinib was studied at the maximal non-toxic concentrations. Both liver and renal PCTS were viable up to 72 hours. Furthermore, after 48 hours of incubation, the early onset of fibrosis was observed in liver PCTS, as demonstrated by an increased expression of Pro-Collagen 1A1 and Heat Shock Protein 47. Moreover, treatment with imatinib for 48 hours did neither impact the gene expression of fibrosis markers nor the protein expression of collagen I in human liver PCTS. Which is in stark disparity to the antifibrotic effects observed in animal models. The gene expression profile of renal PCTS during incubation is currently being evaluated. Thus, human PCTS can be used to study the onset of fibrosis, are promising models to test the efficacy of antifibrotic compounds and can reveal species differences in fibrosis.

Osteogenesis imperfecta (OI) is a heterogeneous rare connective tissue disorder commonly caused by mutations in the collagen type 1 gene. It is a worldwide extensive disorder regardless of age, gender or ethnic group for a children and adults. Typical clinical features are brittle bone, high frequency of fractures and bone deformities. The other observed signs are blue sclera, dentinogenesis imperfect and otosclerosis. In this review, author make a systematic overview, including the mechanisms, classification, diagnostic methods, related to human concerned disease and treatment. The review also focuses on the OI related so many health concern diseases. In OI patients maintaining of health is very important otherwise, the bone deformities and collagen defects common to OI it can affect various internal organs, leading to major or minor secondary problems. Individuals and optimization of OI treatment in children and adults remain a challenge, because available treatments do not target then underlying collagen defect. Treatment includes physiotherapy, surgical procedures and pharmacology therapy. In this brief review, author mainly discusses current knowledge of pharmacology therapies and possible future therapies for treatment of OI.

Risk factors for bone loss in HIV patients might differ or have a different impact in African descent compared to Caucasian populations. The aim of the paper is to analyze the relevance of risk factors on surrogate markers of bone metabolism in HIV-infected African descent and Caucasian patients. This is a cross-sectional study in a single HIV-specialized research and clinical care center in Munich, Germany. We included 889 patients in the study, among them 771 Caucasians (86.7%). Only in Caucasians lower vitamin D levels [OR: 2.5 (95CI: 1.6-3.7)], lower calcium levels [OR: 1.8 (1.2-2.8)], and the use of tenofovir disoproxil fumarate [OR: 2.8 (1.8-4.4)] were significantly associated with elevated PTH in multivariate analysis. Likewise, only in Caucasians elevated PTH was significantly associated with elevated markers of c-terminal telopeptides of collagen type 1 (β-CTX) [OR: 1.7 (1.0-3.0)]. Effects of traditional risk factors for secondary hyperparathyroidism and increased markers of bone turn-over seem to be less distinct in African descent HIV patients. The clinical impact and generalizability of this finding as well as the significance of vitamin D supplementation in African descent patients therefore warrants further investigation.

Facial plastic and reconstructive surgery often used skin graft on defects that cannot be covered primarily by a local flap. However, wound healing using skin graft is slow, most of the time the graft is contractured and the take of graft is not optimal. Platelet rich fibrin matrix (PRFM) is a new generation of concentrated platelets that produce natural fibrin and reported to speed up the healing process. Application of PRFM in the skin graft implants is expected to increase the survival of the graft. We used porcine as animal models to elucidate the effect of autologous PRFM on wound healing in full-thickness (FTSG) and split-thickness (STSG) skin grafts. Survival level of the skin graft was determined by using ImageJ software based on the formation of collagen type 1 and graft take. We observed that the use of PRFM in FTSG and STSG increased type 1 collagen formation. We also found that PRFM addition in STSG gave the best skin graft take.

AIM It is unknown how the heart distinguishes various overloads, such as exercise or hypertension, causing either physiological or pathological hypertrophy. We hypothesize that alpha-calcitonin-gene-related peptide (αCGRP), known to be released from contracting skeletal muscles, is key at this remodelling. METHODS The hypertrophic effect of αCGRP was measured in vitro (cultured cardiac myocytes) and in vivo (magnetic resonance imaging) in mice. Exercise performance was assessed by determination of maximum oxygen consumption and time to exhaustion. Cardiac phenotype was defined by transcriptional analysis, cardiac histology and morphometry. Finally, we measured spontaneous activity, body fat content, blood volume, haemoglobin mass and skeletal muscle capillarization and fibre composition. RESULTS While αCGRP exposure yielded larger cultured cardiac myocytes, exercise-induced heart hypertrophy was completely abrogated by treatment with the peptide antagonist CGRP(8-37). Exercise performance was attenuated in αCGRP(-/-) mice or CGRP(8-37) treated wild-type mice but improved in animals with higher density of cardiac CGRP receptors (CLR-tg). Spontaneous activity, body fat content, blood volume, haemoglobin mass, muscle capillarization and fibre composition were unaffected, whereas heart index and ventricular myocyte volume were reduced in αCGRP(-/-) mice and elevated in CLR-tg. Transcriptional changes seen in αCGRP(-/-) (but not CLR-tg) hearts resembled maladaptive cardiac phenotype. CONCLUSIONS Alpha-calcitonin-gene-related peptide released by skeletal muscles during exercise is a hitherto unrecognized effector directing the strained heart into physiological instead of pathological adaptation. Thus, αCGRP agonists might be beneficial in heart failure patients.

ObjectivesThis study aimed to create a myocardial tissue construct by tissue engineering to repair, replace, and regenerate damaged cardiac tissue.Methods and resultsHuman cardiac muscles harvested from a homograft heart retrieval system were decellularized followed by coating with electrospun nanofibers to make them amenable to scaffolding. These processed cardiac tissues were nourished in modified media having ischemic cardiac tissue conditioned media in 6 separate experimental variants, and cord blood mononuclear cells were injected into 4 of them. On the 17th day of culture, the nanofiber-coated scaffolds injected with mononuclear cells and/or reinforced by electrical and mechanical forces, started contracting spontaneously at varying rates, while the control remain noncontractile. Histological staining confirmed the pre-culture acellularity as well as post-culture stem cell viability, and revealed expression of troponin I and cardiac myosin. The acellular processed scaffold when implanted into sheep ischemic myocardial apex revealed transformation into sheep myocardium after 4 months of implantation.ConclusionThese results provide direct evidence for the re-cellularization of decellularized cardiac tissue grafts reinforced with a polymer nanofiber coating, by human mononuclear cells injection, leading to generation of a tissue-engineered myocardial construct.

Osteogenesis imperfecta (OI) is defined as one of the inherited connective tissue disorders that can result in fragile bones, blue sclera, and deafness. This genetic disease affects collagen type 1 (COL1), which leads to different manifestations depending on the mutation. There are four subtypes of OI, based on different defects in the collagen synthesis, types I, II, III, and IV. OI type I, previously known as OI tarda, is the most common and least severe subtype, is autosomal dominant, and results in blue sclera, increased risk of bone fracture and progressive hearing loss in 50% of patients. OI type II, previously known as OI congenital, is the most severe form, it usually leads to perinatal death and is autosomal recessive. OI Type III is the most severe type among children who survive the neonatal period. The degree of bone fragility and the fracture rate vary widely. OI Type IV diagnosis often occurs later in life and usually represents the patients that do not fit into subtypes I–III (1,2). Deafness is one of the main features of osteogenesis imperfecta and conductive hearing loss is the most common form, but mixed or pure sensorineural hearing losses are not uncommon (3). In the University of Minnesota temporal bone collection, we found one case that fits in the OI diagnosis.

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:30:03Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:43:25Z : No. of bitstreams: 1 2-s2.0-84880335347.pdf: 2379162 bytes, checksum: db53290b788805d40796a665b355e5a3 (MD5) Made available in DSpace on 2014-05-27T11:30:03Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-07-25 Introduction. Tendon injury is a major cause of lameness and decreased performance in athletic equines. Various therapies for tendonitis have been described; however, none of these therapies results in complete tissue regeneration, and the injury recurrence rate is high even after long recovery periods involving rest and physiotherapy. Methods. A lesion was induced with collagenase gel in the superficial digital flexor tendon in the center portion of the metacarpal region of eight equines of mixed breed. After two weeks, the lesions of the animals in the treated and control groups were treated through the intralesional administration of mesenchymal stem cells derived from adipose tissue (adMSCs) suspended in platelet concentrate (PC) and with phosphate buffered saline (PBS), respectively. Serial ultrasound analyses were performed every two weeks. After 16 weeks of therapy, a biopsy was performed for histopathological, immunohistochemical and gene expression (type I collagen (COL1A1), type III collagen (COL3A1), tenascin-C (TNC), tenomodulin (TNMD), and scleraxis (SCX)) analyses. Results: Differences in the ultrasound and histopathological analyses were observed between the groups. Improved results were reported in the group treated with adMSCs suspended in PC. There was no difference in the gene expression levels observed after the different treatments. The main results observed from the histopathological evaluation of the treated group were as follows: a prevention of the progression of the lesion, a greater organization of collagen fibers, and a decreased inflammatory infiltrate. A lack of progression of the lesion area and its percentage was observed in the ultrasound image, and increased blood flow was measured by Power Doppler. Conclusions: The use of adMSCs combined with PC for the therapy of experimentally induced tendonitis prevented the progression of the tendon lesion, as observed in the ultrasound examination, and resulted in a greater organization and decreased inflammation, as observed in the histopathological evaluation. These data demonstrate the therapeutic potential of this therapy for the treatment of equine tendonitis. © 2013 Carvalho et al.; licensee BioMed Central Ltd. Department of Veterinary Surgery and Anesthesiology School of Veterinary Medicine and Animal Science São Paulo State University Rubião Junior, 18618-970 Botucatu, São Paulo Department of Veterinary Clinic School of Veterinary Medicine and Animal Science São Paulo State University Rubião Junior, 18618-970 Botucatu, São Paulo Department of Animal Reproduction and Veterinary Radiology School of Veterinary Medicine and Animal Science São Paulo State University Rubião Junior, 18618-970 Botucatu, São Paulo Blood Center Botucatu Medical School São Paulo State University Rubião Junior, 18618-970 Botucatu, São Paulo Department of Veterinary Surgery and Anesthesiology School of Veterinary Medicine and Animal Science São Paulo State University Rubião Junior, 18618-970 Botucatu, São Paulo Department of Veterinary Clinic School of Veterinary Medicine and Animal Science São Paulo State University Rubião Junior, 18618-970 Botucatu, São Paulo Department of Animal Reproduction and Veterinary Radiology School of Veterinary Medicine and Animal Science São Paulo State University Rubião Junior, 18618-970 Botucatu, São Paulo Blood Center Botucatu Medical School São Paulo State University Rubião Junior, 18618-970 Botucatu, São Paulo

AimsWe explored the use of highly purified murine and human pluripotent stem cell (PSC)-derived cardiomyocytes (CMs) to generate functional bioartificial cardiac tissue (BCT) and investigated the role of fibroblasts, ascorbic acid (AA), and mechanical stimuli on tissue formation, maturation, and functionality.Methods and resultsMurine and human embryonic/induced PSC-derived CMs were genetically enriched to generate three-dimensional CM aggregates, termed cardiac bodies (CBs). Addressing the critical limitation of major CM loss after single-cell dissociation, non-dissociated CBs were used for BCT generation, which resulted in a structurally and functionally homogenous syncytium. Continuous in situ characterization of BCTs, for 21 days, revealed that three critical factors cooperatively improve BCT formation and function: both (i) addition of fibroblasts and (ii) ascorbic acid supplementation support extracellular matrix remodelling and CB fusion, and (iii) increasing static stretch supports sarcomere alignment and CM coupling. All factors together considerably enhanced the contractility of murine and human BCTs, leading to a so far unparalleled active tension of 4.4 mN/mm2 in human BCTs using optimized conditions. Finally, advanced protocols were implemented for the generation of human PSC-derived cardiac tissue using a defined animal-free matrix composition.ConclusionBCT with contractile forces comparable with native myocardium can be generated from enriched, PSC-derived CMs, based on a novel concept of tissue formation from non-dissociated cardiac cell aggregates. In combination with the successful generation of tissue using a defined animal-free matrix, this represents a major step towards clinical applicability of stem cell-based heart tissue for myocardial repair. © 2013 The Author.

Background: The mechanisms involved in cardiac remodeling in left (LV) and right ventricles (RV) after myocardial infarction (MI) are still unclear. We assayed factors involved in collagen turnover in both ventricles following MI in rats either presenting signs of heart failure (pulmonary congestion and increased LVEDP) or not (INF-HF or INF, respectively). Methods: MI was induced in male rats by ligation of the left coronary artery. Four weeks after MI gene expression of collagen I, connective tissue growth factor (CTGF), transforming growth factor beta (TGF-beta) and lysyl oxidase (LOX), metalloproteinase-2 (MMP2) and tissue inhibitor metalloproteinase-2 (TIMP2) as well as cardiac hemodynamic in both ventricles were evaluated. Results: Ventricular dilatation, hypertrophy and an increase in interstitial fibrosis and myocyte size were observed in the RV and LV from INF-HF animals, whereas only LV dilatation and fibrosis in RV was present in INF. The LV fibrosis in INF-HF was associated with higher mRNA of collagen I, CTGF, TGF-beta and LOX expressions than in INF and SHAM animals, while MMP2/TIMP2 mRNA ratio did not change. RV fibrosis in INF and INF-HF groups was associated with an increase in LOX mRNA and a reduction in MMP2/TIMP2 ratio. CTGF mRNA was increased only in the INF-HF group. Conclusions: INF and INF-HF animals presented different patterns of remodeling in both ventricles. In the INF-HF group, fibrosis seems to be consequence of collagen production in LV, and by reductions in collagen degradation in RV of both INF and INF-HF animals.

Gene therapy for hemophilia B and other hereditary plasma protein deficiencies showed great promise in pre-clinical and early clinical trials. However, safety concerns about in vivo delivery of viral vectors and poor post-transplant survival of ex vivo modified cells remain key hurdles for clinical translation of gene therapy. We here describe a 3D scaffold system based on porous hydroxyapatite-PLGA composites coated with biomineralized collagen 1. When combined with autologous gene-engineered factor IX (hFIX) positive mesenchymal stem cells (MSCs) and implanted in hemophilic mice, these scaffolds supported long-term engraftment and systemic protein delivery by MSCs in vivo. Optimization of the scaffolds at the macro-, micro- and nanoscales provided efficient cell delivery capacity, MSC self-renewal and osteogenesis respectively, concurrent with sustained delivery of hFIX. In conclusion, the use of gene-enhanced MSC-seeded scaffolds may be of practical use for treatment of hemophilia B and other plasma protein deficiencies. © 2010 Elsevier Ltd.

Protrusio acetabuli (PA) is a rare cause of hip pain which manifests itself in the radiological investigation as intrapelvic protrusion of the acetabulum. It may be caused by a variety of etiopathogenetic factors. In this article, we aimed to present a-20-year-old young patient who presented to our outpatient clinic with complaints of bilateral hip pain, was diagnosed with PA in hip joints caused by primary osteoporosis and was shown to have polymorphism within the Collagen type 1 alpha 1 (COL1A1) Sp1-binding site by osteoporosis gene analysis. (Turkish Journal of Osteoporosis 2014;20: 135-6)

BACKGROUND: There is growing interest in soluble biomarkers that could be used on the group level for screening purposes in small proof of principle studies during early drug development. We investigated early changes in serum levels of several candidate biomarkers involved in cartilage and bone metabolism following the initiation of adalimumab as a prototypic active treatment in psoriatic arthritis (PsA) compared to placebo. MATERIALS AND METHODS: Twenty-four PsA patients were randomized to receive either adalimumab 40 mg s.c. every other week or placebo for 4 weeks, followed by an open label extension phase. Serum samples were obtained at baseline and after 4 and 12 weeks of treatment and analyzed for levels of CPII and PINP (synthesis of type II and type I procollagen), melanoma inhibitory activity (MIA) (chondrocyte anabolism), matrix metalloproteinase (MMP)-3, C2C and cartilage oligomeric matrix protein (COMP) (type II collagen degradation), osteocalcin (OC) (bone formation), NTX-I and ICTP (both type I collagen degradation). RESULTS: After 4 weeks, there was a significant decrease in serum MMP-3 levels in adalimumab-treated patients (P