Characterization of bone repair in rat femur after treatment with calcium phosphate cement and autogenous bone graft

<p>Abstract</p> <p>Background</p> <p>In this study, the biocompatibility, stability and osteotransductivity of a new cement based on alpha-tricalcium phosphate (alpha-TCP) were investigated in a bone repair model using a rat model.</p> <p>Methods</p> <p>The potential of alpha-TCP on bone repair was compared to autogenous bone grafting, and unfilled cavities were used as negative control. Surgical cavities were prepared and designated as test (T), implanted with alpha-TCP blocks; negative control (C - ), unfilled; and positive control (C + ), implanted with autogenous bone graft. Results were analyzed on postoperative days three, seven, 14, 21 and 60.</p> <p>Results</p> <p>The histological analyses showed the following results. Postoperative day three: presence of inflammatory infiltrate, erythrocytes and proliferating fibroblasts in T, C - and C + samples. Day seven: extensive bone neoformation in groups T and C + , and beginning of alpha-TCP resorption by phagocytic cells. Days 14 and 21: osteoblastic activity in the three types of cavities. Day 60: In all samples, neoformed bone similar to surrounding bone. Moderate interruption on the ostectomized cortical bone.</p> <p>Conclusions</p> <p>Bone neoformation is seen seven days after implantation of alpha-TCP and autogenous bone. Comparison of C - with T and C + samples showed that repair is faster in implanted cavities; on day 60, control groups presented almost complete bone repair. Alpha-TCP cement presents biocompatibility and osteotransductivity, besides stability, but 60 days after surgery the cavities were not closed.</p

Heregulin inhibits proliferation via ERKs and phosphatidyl-inositol 3-kinase activation but regulates urokinase plasminogen activator independently of these pathways in metastatic mammary tumor cells

Heregulin (HRG) and type I receptor tyrosine kinase (RTK) expression was investigated in the highly invasive and metastatic LM3 cell line, our previously described model of metastasis for mammary cancer (Bal de Kier Joffe et al. [1986] Invasion Metastasis 6:302-12; Urtreger et al. [1997] Int J Oncol 11:489-96). Although LM3 cells do not express HRG, they exhibit high levels of ErbB-2 and ErbB-3 as well as moderate expression of ErbB-4. Addition of exogenous HRGβ1 resulted in inhibition of both proliferation and migration of LM3 cells. HRGβ1 was also able to decrease the activity of urokinase-type plasminogen activator (uPA) and matrix metalloproteinase 9 (MMP-9), 2 key enzymes in the invasion and metastatic cascade. HRGβ1 treatment of LM3 cells induced tyrosine phosphorylation of ErbB-2, ErbB-3 and ErbB-4 as well as the formation of ErbB-2/ErbB-3 and ErbB-2/ErbB-4 heterodimers. Assessment of the signaling pathways involved in HRGβ1 action indicated that the addition of HRGβ1 to LM3 cells resulted in activation of phosphatidylinositol 3-kinase (PI-3K) and in strong induction of the association of the p85 subunit of PI-3K with ErbB-3. HRGβ1 also caused the rapid activation of ERKI/ERK2 and Stat3 and Stat5 (signal transducers and activators of transcription [STAT]). This is the first demonstration of the ability of HRGβ1 to activate STATs in mammary tumor cells. Blockage of PI-3K activity with its chemical inhibitor wortmannin, or of MEKI/ERKs activity with PD98059, resulted in suppression of the ability of HRGβ1 to inhibit LM3 cell growth. Notwithstanding the suppression of these 2 signaling pathways, HRGβ1 still proved capable of inhibiting uPA activity. Therefore, our results provide evidence that signaling pathways involved in HRGβ1-induced proliferation appear to be distinct from those involved in HRGβ1 regulation of uPA, a protease that plays a pivotal role in invasion and metastasis. © 2002 Wiley-Liss, Inc.Fil:Puricelli, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Labriola, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Salatino, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Balañá, M.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Pignataro, O.P. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Charreau, E.H. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Elizalde, P.V. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

Interruption of cancer screening services due to COVID-19 pandemic: lessons from previous disasters

Purpose: To review the scientific literature seeking lessons for the COVID-19 era that could be learned from previous health services interruptions that affected the delivery of cancer screening services. Methods: A systematic search was conducted up to April 17, 2020, with no restrictions on language or dates and resulted in 385 articles. Two researchers independently assessed the list and discussed any disagreements. Once a consensus was achieved for each paper, those selected were included in the review. Results: Eleven articles were included. Three studies were based in Japan, two in the United States, one in South Korea, one in Denmark, and the remaining four offered a global perspective on interruptions in health services due to natural or human-caused disasters. No articles covered an interruption due to a pandemic. The main themes identified in the reviewed studies were coordination, communication, resource availability and patient follow-up. Conclusion: Lessons learned applied to the context of COVID-19 are that coordination involving partners across the health sector is essential to optimize resources and resume services, making them more resilient while preparing for future interruptions. Communication with the general population about how COVID-19 has affected cancer screening, measures taken to mitigate it and safely re-establish screening services is recommended. Use of mobile health systems to reach patients who are not accessing services and the application of resource-stratified guidelines are important considerations. More research is needed to explore best strategies for suspending, resuming and sustaining cancer screening programs, and preparedness for future disruptions, adapted to diverse health care systems

Clinical impact of videocapsule endoscopy and device-assisted enteroscopy in non-bleeding small bowel lesions

Background: Videocapsule endoscopy (VCE) and double-balloon enteroscopy (DBE) are part of the diagnostic and therapeutic work-up of indications other than suspected small bowel bleeding (OSBB). The literature is currently lacking studies describing these procedures in this particular setting. Objectives: We assessed the clinical impact of VCE and DBE in a large monocentric cohort of OSBB patients, as compared to a control group of suspected small bowel bleeding (SSBB) patients who underwent enteroscopy over the same period. Design: Monocentric, retrospective, cohort study. Methods: We collected the data of consecutive patients with OSBB undergoing VCE and/or DBE from March 2001 to July 2020. The demographic and clinical parameters of the patients, technical characteristics, and adverse events for each procedure were collected. The impact of VCE and DBE was defined in terms of diagnostic yield (DY). The patients were subdivided according to the main indication into four groups: celiac disease, Crohn’s disease (CD), neoplasia, and persistent gastrointestinal symptoms. Results: A total of 611 VCEs and 387 DBEs were performed for OSBB. The main indications were complicated celiac disease and CD. The DYs of VCE and DBE overall were 53 and 61.7%, respectively, with some variance among the four groups. We report no statistical differences in the DY of VCE and DBE in SSBB vs OSBB (57.7% vs 53%, p = 0.0859 and 68.8% vs 61.7%, p = 0.0582, respectively). OSBB patients were significantly younger than those with SSBB. However, similarly to SSBB (k = 0.059), poor agreement between the enteroscopic techniques was found in the OSBB population (k = 0.109). The safety of both procedures in OSBB was comparable to that in SSBB patients. Conclusion: VCE and DBE are effective and safe in suspected OSBB, where their role is similar to that in SSBB, their main indication

Mouse mammary tumors display Stat3 activation dependent on leukemia inhibitory factor signaling

Introduction: It has been demonstrated that leukemia inhibitory factor (LIF) induces epithelium apoptosis through Stat3 activation during mouse mammary gland involution. In contrast, it has been shown that this transcription factor is commonly activated in breast cancer cells, although what causes this effect remains unknown. Here we have tested the hypothesis that locally produced LIF can be responsible for Stat3 activation in mouse mammary tumors. Methods: The studies were performed in different tumorigenic and non-tumorigenic mammary cells. The expression of LIF and LIF receptor was tested by RT-PCR analysis. In tumors, LIF and Stat3 proteins were analyzed by immunohistochemistry, whereas Stat3 and extracellular signal-regulated kinase (ERK)1/2 expression and phosphorylation were studied by Western blot analysis. A LIF-specific blocking antibody was used to determine whether this cytokine was responsible for Stat3 phosphorylation induced by conditioned medium. Specific pharmacological inhibitors (PD98059 and Stat3ip) that affect ERK1/2 and Stat3 activation were used to study their involvement in LIF-induced effects. To analyze cell survival, assays with crystal violet were performed. Results: High levels of LIF expression and activated Stat3 were found in mammary tumors growing in vivo and in their primary cultures. We found a single mouse mammary tumor cell line, LM3, that showed low levels of activated Stat3. Incidentally, these cells also showed very little expression of LIF receptor. This suggested that autocrine/paracrine LIF would be responsible for Stat3 activation in mouse mammary tumors. This hypothesis was confirmed by the ability of conditioned medium of mammary tumor primary cultures to induce Stat3 phosphorylation, activity that was prevented by pretreatment with LIF-blocking antibody. Besides, we found that LIF increased tumor cell viability. Interestingly, blocking Stat3 activation enhanced this effect in mammary tumor cells. Conclusion: LIF is overexpressed in mouse mammary tumors, where it acts as the main Stat3 activator. Interestingly, the positive LIF effect on tumor cell viability is not dependent on Stat3 activation, which inhibits tumor cell survival as it does in normal mammary epithelium. © 2007 Quaglino et al.; licensee BioMed Central Ltd.Fil:Quaglino, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Schere-Levy, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Romorini, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Kordon, E.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

Effects of a buried magnetic field on cranial bone reconstruction in rats

ABSTRACT The understanding of bone repair phenomena is a fundamental part of dentistry and maxillofacial surgery. Objective The present study aimed to evaluate the influence of buried magnetic field stimulation on bone repair in rat calvaria after reconstruction with autogenous bone grafts, synthetic powdered hydroxyapatite, or allogeneic cartilage grafts, with or without exposure to magnetic stimulation. Material and Methods Ninety male Wistar rats were divided into 18 groups of five animals each. Critical bone defects were created in the rats’ calvaria and immediately reconstructed with autogenous bone, powdered synthetic hydroxyapatite or allogeneic cartilage. Magnetic implants were also placed in half the animals. Rats were euthanized for analysis at 15, 30, and 60 postoperative days. Histomorphometric analyses of the quantity of bone repair were performed at all times. Results These analyses showed significant group by postoperative time interactions (p=0.008). Among the rats subjected to autogenous bone reconstruction, those exposed to magnetic stimulation had higher bone fill percentages than those without magnetic implants. Results also showed that the quality of bone repair remained higher in the former group as compared to the latter at 60 postoperative days. Conclusions After 60 postoperative days, bone repair was greater in the group treated with autogenous bone grafts and exposed to a magnetic field, and bone repair was most pronounced in animals treated with autogenous bone grafts, followed by those treated with powdered synthetic hydroxyapatite and allogeneic cartilage grafts

Insight on colorectal carcinoma infiltration by studying perilesional extracellular matrix

The extracellular matrix (ECM) from perilesional and colorectal carcinoma (CRC), but not healthy colon, sustains proliferation and invasion of tumor cells. We investigated the biochemical and physical diversity of ECM in pair-wised comparisons of healthy, perilesional and CRC specimens. Progressive linearization and degree of organization of fibrils was observed from healthy to perilesional and CRC ECM, and was associated with a steady increase of stiffness and collagen crosslinking. In the perilesional ECM these modifications coincided with increased vascularization, whereas in the neoplastic ECM they were associated with altered modulation of matrisome proteins, increased content of hydroxylated lysine and lysyl oxidase. This study identifies the increased stiffness and crosslinking of the perilesional ECM predisposing an environment suitable for CRC invasion as a phenomenon associated with vascularization. The increased stiffness of colon areas may represent a new predictive marker of desmoplastic region predisposing to invasion, thus offering new potential application for monitoring adenoma with invasive potential

Scale invariant disordered nanotopography promotes hippocampal neuron development and maturation with involvement of mechanotransductive pathways

The identification of biomaterials which promote neuronal maturation up to the generation of integrated neural circuits is fundamental for modern neuroscience. The development of neural circuits arises from complex maturative processes regulated by poorly understood signaling events, often guided by the extracellular matrix (ECM). Here we report that nanostructured zirconia surfaces, produced by supersonic cluster beam deposition of zirconia nanoparticles and characterized by ECM-like nanotopographical features, can direct the maturation of neural networks. Hippocampal neurons cultured on such cluster-assembled surfaces displayed enhanced differentiation paralleled by functional changes. The latter was demonstrated by single-cell electrophysiology showing earlier action potential generation and increased spontaneous postsynaptic currents compared to the neurons grown on the featureless unnaturally flat standard control surfaces. Label-free shotgun proteomics broadly confirmed the functional changes and suggests furthermore a vast impact of the neuron/nanotopography interaction on mechanotransductive machinery components, known to control physiological in vivo ECM-regulated axon guidance and synaptic plasticity. Our results indicate a potential of cluster-assembled zirconia nanotopography exploitable for the creation of efficient neural tissue interfaces and cell culture devices promoting neurogenic events, but also for unveiling mechanotransductive aspects of neuronal development and maturation