A new heterologous fibrin sealant as a scaffold to cartilage repair - experimental study and preliminary results

Autologous fibrin gel is commonly used as a scaffold for filling defects in articular cartilage. This biomaterial can also be used as a sealant to control small hemorrhages and is especially helpful in situations where tissue reparation capacity is limited. In particular, fibrin can act as a scaffold for various cell types because it can accommodate cell migration, differentiation, and proliferation. Despite knowledge of the advantages of this biomaterial and mastery of the techniques required for its application, the durability of several types of sealant at the site of injury remains questionable. Due to the importance of such data for evaluating the quality and efficiency of fibrin gel formulations on its use as a scaffold, this study sought to analyze the heterologous fibrin sealant developed from the venom of Crotalus durissus terrificus using studies in ovine experimental models. The fibrin gel developed from the venom of this snake was shown to act as a safe, stable, and durable scaffold for up to seven days, without causing adverse side effects. Fibrin gel produced from the venom of the Crotalus durissus terrificus snake possesses many clinical and surgical uses. It presents the potential to be used as a biomaterial to help repair skin lesions or control bleeding, and it may also be used as a scaffold when applied together with various cell types. The intralesional use of the fibrin gel from the venom of this snake may improve surgical and clinical treatments in addition to being inexpensive and adequately consistent, durable, and stable. The new heterologous fibrin sealant is a scaffold candidate to cartilage repair in this study.

Bone defect repair on the alveolar wall of the maxillary sinus using collagen membranes and temporal fascia: an experimental study in monkeys

Few studies has been done using guided bone regeneration in maxillary sinus defects. AIM: To assess the bone repair process in surgical defects on the alveolar wall of the monkey maxillary sinus, which communicates with the sinus cavity, by using collagen membranes: Gen-derm - Genius Baumer, Pro-tape - Proline and autologous temporal fascia. MATERIALS AND METHODS: In this prospective and experimental study, orosinusal communications were performed in four tufted capuchin monkeys (Cebus apella) and histologic analysis was carried out 180 days after. RESULTS: In the defects without a cover (control), bone proliferation predominated in two animals and fibrous connective tissue predominated in the other two. In defects repaired with a temporal fascia flap, fibrous connective tissue predominated in three animals and bone proliferation predominated in one. In the defects repaired with Gen-derm or Pro-tape collagen membranes there was complete bone proliferation in three animals and fibrous connective tissue in one. CONCLUSIONS: Surgical defect can be repaired with both bone tissue and fibrous connective tissue in all study groups; collagen membranes was more beneficial in the bone repair process than temporal fascia or absence of a barrier.

Endovascular repair of a juxtarenal saccular aneurysm using the Multilayer Flow Modulator: report of the first case performed in a Public Hospital in Brazil

Endovascular aortic aneurysm repair (EVAR) involving renal and visceral arteries remains a great challenge. Several techniques have been developed over the time to treat juxtarenal, pararenal and thoracoabdominal aneurysms, highlighting the fenestrated and branched endografts, parallel prostheses as Chimney, Periscope and Sandwich Techniques and the use of flow modulation by multilayer stent. We report a case of saccular juxtarenal aortic aneurysm with high surgical risk for complex airway access due to a history of radical laryngectomy for laryngeal neoplasm. Due to chronic aorto-iliac obstructive disease, ostial stenosis of renal artery and limited diameter of the suprarenal aorta, we discarded options involving fenestrated/branched endografts and involving parallel prostheses techniques. We present this case as a therapeutic challenge and a successful treatment option in the short-term evaluation.

Unfavorable iliac artery anatomy causing access limitations during endovascular abdominal aortic aneurysm repair: application of the endoconduit technique

Endovascular aneurysm repair (EVAR) is already considered the first choice treatment for abdominal aortic aneurysms (AAA). Several different strategies have been used to address limitations to arterial access caused by unfavorable iliac artery anatomy. The aim of this report is to illustrate the advantages and limitations of each option and present the results of using the internal endoconduit technique and the difficulties involved.

Effect of soft laser in bone repair after expansion of the midpalatal suture in dogs

Introduction: The purpose of this research was to study the influence of soft laser treatment on the process of bone repair after expansion of the midpalatal suture. Methods: The sample for this case-control experimental study was 11 dogs. They were randomly divided into 2 groups, both of which underwent rapid maxillary expansion with a hyrax appliance. The animals in group 1 were also treated with laser therapy. They were killed, and histologic specimens of the palatal suture were prepared. The Student t test was applied for independent data, and the Mann-Whitney test was used for nonparametric data. Results: A significant difference was observed in the quality of the palatal sutures between the animals in groups 1 and 2. The connective tissues of the sutures in the group 1 animals were similar to the original configurations, with more advanced osteogenesis and fibrogenesis, compared with those of group 2. Conclusions: Soft laser appears to influence the behavior of the repair process, contributing to suture reorganization and palatal bone osteogenesis during and after expansion. (Am J Orthod Dentofacial Orthop 2012; 142: 615-24)

Predictive models for mutations in mismatch repair genes: implication for genetic counseling in developing countries

Background: Lynch syndrome (LS) is the most common form of inherited predisposition to colorectal cancer (CRC), accounting for 2-5% of all CRC. LS is an autosomal dominant disease characterized by mutations in the mismatch repair genes mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), postmeiotic segregation increased 1 (PMS1), post-meiotic segregation increased 2 (PMS2) and mutS homolog 6 (MSH6). Mutation risk prediction models can be incorporated into clinical practice, facilitating the decision-making process and identifying individuals for molecular investigation. This is extremely important in countries with limited economic resources. This study aims to evaluate sensitivity and specificity of five predictive models for germline mutations in repair genes in a sample of individuals with suspected Lynch syndrome. Methods: Blood samples from 88 patients were analyzed through sequencing MLH1, MSH2 and MSH6 genes. The probability of detecting a mutation was calculated using the PREMM, Barnetson, MMRpro, Wijnen and Myriad models. To evaluate the sensitivity and specificity of the models, receiver operating characteristic curves were constructed. Results: Of the 88 patients included in this analysis, 31 mutations were identified: 16 were found in the MSH2 gene, 15 in the MLH1 gene and no pathogenic mutations were identified in the MSH6 gene. It was observed that the AUC for the PREMM (0.846), Barnetson (0.850), MMRpro (0.821) and Wijnen (0.807) models did not present significant statistical difference. The Myriad model presented lower AUC (0.704) than the four other models evaluated. Considering thresholds of >= 5%, the models sensitivity varied between 1 (Myriad) and 0.87 (Wijnen) and specificity ranged from 0 (Myriad) to 0.38 (Barnetson). Conclusions: The Barnetson, PREMM, MMRpro and Wijnen models present similar AUC. The AUC of the Myriad model is statistically inferior to the four other models.

DNA repair mechanisms protect our genome from carcinogenesis

Human cells are constantly exposed to DNA damage. Without repair, damage can result in genetic instability and eventually cancer. The strong association between the lack of DNA damage repair, mutations and cancer is dramatically demonstrated by a number of cancer-prone human syndromes, such as xeroderma pigmentosum (XP), ataxia-telangiectasia (AT) and Fanconi anemia (FA). This review focuses on the historical discoveries related with these three diseases and describes their impact on the understanding of DNA repair mechanisms and the causes of human cancer. As deficiencies in DNA repair are also often related with progeria symptoms, unrepaired damage and aging are somehow related. Several other pathologies associated with DNA repair defects, genetic instability and increased cancer risk are also discussed. In fact, studies with cells from these many syndromes have helped in understanding important levels of protection against cancer and aging, although little help has actually been conferred to the patients in terms of therapy. Finally, the recent advances in combined basic and translational research on DNA repair and chemotherapy are presented.

Extrinsic Purinergic Regulation of Neural Stem/Progenitor Cells: Implications for CNS Development and Repair

There has been tremendous progress in understanding neural stem cell (NSC) biology, with genetic and cell biological methods identifying sequential gene expression and molecular interactions guiding NSC specification into distinct neuronal and glial populations during development. Data has emerged on the possible exploitation of NSC-based strategies to repair adult diseased brain. However, despite increased information on lineage specific transcription factors, cell-cycle regulators and epigenetic factors involved in the fate and plasticity of NSCs, understanding of extracellular cues driving the behavior of embryonic and adult NSCs is still very limited. Knowledge of factors regulating brain development is crucial in understanding the pathogenetic mechanisms of brain dysfunction. Since injury-activated repair mechanisms in adult brain often recapitulate ontogenetic events, the identification of these players will also reveal novel regenerative strategies. Here, we highlight the purinergic system as a key emerging player in the endogenous control of NSCs. Purinergic signalling molecules (ATP, UTP and adenosine) act with growth factors in regulating the synchronized proliferation, migration, differentiation and death of NSCs during brain and spinal cord development. At early stages of development, transient and time-specific release of ATP is critical for initiating eye formation; once anatomical CNS structures are defined, purinergic molecules participate in calcium-dependent neuron-glia communication controlling NSC behaviour. When development is complete, some purinergic mechanisms are silenced, but can be re-activated in adult brain after injury, suggesting a role in regeneration and self-repair. Targeting the purinergic system to develop new strategies for neurodevelopmental disorders and neurodegenerative diseases will be also discussed.

Constitutive models for biodegradable thermoplastic ropes for ligament repair

The concept behind a biodegradable ligament device is to temporarily replace the biomechanical functions of the ruptured ligament, while it progressively regenerates its capacities. However, there is a lack of methods to predict the mechanical behaviour evolution of the biodegradable devices during degradation, which is an important aspect of the project. In this work, a hyper elastic constitutive model will be used to predict the mechanical behaviour of a biodegradable rope made of aliphatic polyesters. A numerical approach using ABAQUS is presented, where the material parameters of the model proposal are automatically updated in correspondence to the degradation time, by means of a script in PYTHON. In this method we also use a User Material subroutine (UMAT) to apply a failure criterion base on the strength that decreases according to a first order differential equation. The parameterization of the material model proposal for different degradation times were achieved by fitting the theoretical curves with the experimental data of tensile tests on fibres. To model all the rope behaviour we had considered one step of homogenisation considering the fibres architectures in an elementary volume. (C) 2012 Elsevier Ltd. All rights reserved.

Variation in DNA repair gene XRCC3 affects susceptibility to astrocytomas and glioblastomas

The gene XRCC3 (X-ray cross complementing group 3) has the task of repairing damage that occurs when there is recombination between homologous chromosomes. Repair of recombination between homologous chromosomes plays an important role in maintaining genome integrity, although it is known that double-strand breaks are the main inducers of chromosomal aberrations. Changes in the XRCC3 protein lead to an increase in errors in chromosome segregation due to defects in centrosomes, resulting in aneuploidy and other chromosomal aberrations, such as small increases in telomeres. We examined XRCC3 Thr241Met polymorphism using PCR-RFLP in 80 astrocytoma and glioblastoma samples. The individuals of the control group (N = 100) were selected from the general population of the Sao Paulo State. Odds ratio and 95%CI were calculated using a logistic regression model. Patients who had the allele Met of the XRCC3 Thr241Met polymorphism had a significantly increased risk of tumor development (odds ratio = 3.13; 95% confidence interval = 1.50-6.50). There were no significant differences in overall survival of patients. We suggest that XRCC3 Thr241Met polymorphism is involved in susceptibility for developing astrocytomas and glioblastomas.

Both XPA and DNA polymerase eta are necessary for the repair of doxorubicin-induced DNA lesions

Doxorubicin (DOX) is an important tumor chemotherapeutic agent, acting mainly by genotoxic action. This work focus on cell processes that help cell survival, after DOX-induced DNA damage. In fact, cells deficient for XPA or DNA polymerase eta (pol eta, XPV) proteins (involved in distinct DNA repair pathways) are highly DOX-sensitive. Moreover, LY294002, an inhibitor of PIKK kinases, showed a synergistic killing effect in cells deficient in these proteins, with a strong induction of G2/M cell cycle arrest. Taken together, these results indicate that XPA and pol eta proteins participate in cell resistance to DOX-treatment, and kinase inhibitors can selectively enhance its killing effects, probably reducing the cell ability to recover from breaks induced in DNA. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Comparative study of bone repair in mandibular body osteotomy between metallic and absorbable 2.0 mm internal fixation systems. Histological and histometric analysis in dogs: a pilot study

The objective of this study was to compare the bone repair along a mandibular body osteotomy stabilized with 2.0 mm absorbable and metallic systems. 12 male, adult mongrel dogs were divided into two groups (metallic and absorbable) and subjected to unilateral osteotomy between the mandibular third and fourth premolars, which was stabilized by applying two 4-hole plates. At 2 and 18 weeks, three dogs from each group were killed and the osteotomy sites were removed and divided equally into three parts: the upper part was labelled the tension third (TT), the lower part the compression third (CT), and the part between the TT and CT the intermediary third (IT). Regardless of the treatment system, union between the fragments was observed at 18 weeks and the CT showed more advanced stages of bone repair than the TT. Histometric analysis did not reveal any significant differences among the 3 parts or systems in the distance between bone fragments at 2 weeks. Although at 18 weeks the proportions of newly formed bone did not differ among TT, IT and CT, significantly enhanced bone formation was observed in all sections for the metallic group. The patterns of repair were distinct between treatments.

Targeting the Transposase Domain of the DNA Repair Component Metnase to Enhance Chemotherapy

Previous studies have shown that the DNA repair component Metnase (SETMAR) mediates resistance to DNA damaging cancer chemotherapy. Metnase has a nuclease domain that shares homology with the Transposase family. We therefore virtually screened the tertiary Metnase structure against the 550,000 compound ChemDiv library to identify small molecules that might dock in the active site of the transposase nuclease domain of Metnase. We identified eight compounds as possible Metnase inhibitors. Interestingly, among these candidate inhibitors were quinolone antibiotics and HIV integrase inhibitors, which share common structural features. Previous reports have described possible activity of quinolones as antineoplastic agents. Therefore, we chose the quinolone ciprofloxacin for further study, based on its wide clinical availability and low toxicity. We found that ciprofloxacin inhibits the ability of Metnase to cleave DNA and inhibits Metnase-dependent DNA repair. Ciprofloxacin on its own did not induce DNA damage, but it did reduce repair of chemotherapy-induced DNA damage. Ciprofloxacin increased the sensitivity of cancer cell lines and a xenograft tumor model to clinically relevant chemotherapy. These studies provide a mechanism for the previously postulated antineoplastic activity of quinolones, and suggest that ciprofloxacin might be a simple yet effective adjunct to cancer chemotherapy. Cancer Res; 72(23); 6200-8. (C) 2012 AACR.

Endovascular repair of a traumatic arteriovenous fistula involving the iliac bifurcation using an iliac branch device

Endovascular techniques have shown to be useful in the management of vascular injuries because they transform a complex and potentially dangerous procedure into a safe one. We present the case of a 39-year-old man with congestive heart failure and abdominal bruit 11 years after an abdominal gunshot wound. Imaging studies revealed an arteriovenous fistula involving the left iliac artery bifurcation, and an iliac branch device was used to treat it. Symptoms resolved, and follow-up imaging showed patency of the graft and closure of the arteriovenous communication. To our knowledge, this is the first report of a nonaneurysmal disease treated with this device. (J Vasc Surg 2012;55:1474-6.)