Medication-related osteonecrosis of the jaw: A disease of significant importance for older patients.

Background: Medication-related osteonecrosis of the jaw (MRONJ) is clinically defined as a non-healing jawbone ulcerative-necrotic lesion appearing after dental therapy or minor trauma in patients treated previously with anti-resorptive, anti-angiogenic or immunomodulators. Older patients with osteoporosis and cancer receive these pharmacological agents regularly. As these patients are long-term survivors, efficient treatment is of paramount importance for their quality of life.

Local delivery of hydrogel encapsulated vascular endothelial growth factor for the prevention of medication-related osteonecrosis of the jaw.

The anti-angiogenic effects of bisphosphonates have been hypothesized as one of the major etiologic factors in the development of medication-related osteonecrosis of the jaw (MRONJ), a severe debilitating condition with limited treatment options. This study evaluated the potential of a gelatine-hyaluronic acid hydrogel loaded with the angiogenic growth factor, vascular endothelial growth factor (VEGF), as a local delivery system to aid in maintaining vascularization in a bisphosphonate-treated (Zoledronic Acid) rodent maxillary extraction defect. Healing was assessed four weeks after implantation of the VEGF-hydrogel into extraction sockets.

Extracellular Alpha-Synuclein Promotes a Neuroinhibitory Secretory Phenotype in Astrocytes.

Multiple system atrophy (MSA) and dementia with Lewy bodies (DLB) are α-synucleinopathies that exhibit widespread astrogliosis as a component of the neuroinflammatory response. Munc18, a protein critical to vesicle exocytosis, was previously found to strongly mark morphologically activated astrocytes in brain tissue of MSA patients. Immunofluorescence of MSA, DLB and normal brain tissue sections was combined with cell culture and co-culture experiments to investigate the relationship between extracellular α-synuclein and the transition to a secretory astrocyte phenotype.

Ageing as a risk factor for cerebral ischemia: Underlying mechanisms and therapy in animal models and in the clinic.

Age is the only one non-modifiable risk of cerebral ischemia. Advances in stroke medicine and behavioral adaptation to stroke risk factors and comorbidities was successful in decreasing stroke incidence and increasing the number of stroke survivors in western societies. Comorbidities aggravates the outcome after cerebral ischemia.

Dietary habits, lifestyle factors and neurodegenerative diseases.

Worldwide stroke is increasing in parallel with modernization, changes in lifestyle, and the growing elderly population. Our review is focused on the link between diet, as part of 'modern lifestyle', and health in the context of genetic predisposition of individuals to 'unhealthy' metabolic pathway activity. It is concluded that lifestyle including high sugar diets, alcohol and tobacco addiction or high fat diets as well as ageing, brain injury, oxidative stress and neuroinflammation, negatively influence the onset, severity and duration of neurodegenerative diseases.

3D printing strategies for peripheral nerve regeneration.

After many decades of biomaterials research for peripheral nerve regeneration, a clinical product (the nerve guide), is emerging as a proven alternative for relatively short injury gaps. This review identifies aspects where 3D printing can assist in improving long-distance nerve guide regeneration strategies. These include (1) 3D printing of the customizable nerve guides, (2) fabrication of scaffolds that fill nerve guides, (3) 3D bioprinting of cells within a matrix/bioink into the nerve guide lumen and the (4) establishment of growth factor gradients along the length a nerve guide.

Photochemically Induced Crosslinking of Tarsal Collagen as a Treatment for Eyelid Laxity: Assessing Potentiality in Animal Tissue.

Purpose: An experimental study to demonstrate in animal eyelids that the controlled exposure of excised tarsal plate to ultraviolet-A radiation can induce a rigidification effect due to photochemical crosslinking of the constitutive collagen.

Methods: Excised strips of sheep tarsus were irradiated with ultraviolet-A rays (wavelength 365 nm) at low and high irradiances, in the presence of riboflavin as a photosensitizer, using radiation sources available for corneal collagen crosslinking procedure. The tensile strength and Young's modulus (stiffness) of irradiated and control samples were measured in a mechanical tester and analyzed statistically.

Cellular and Molecular Mechanisms Underlying Non-Pharmaceutical Ischemic Stroke Therapy in Aged Subjects.

Unlabelled: The incidence of ischemic stroke in humans increases exponentially above 70 years both in men and women. Comorbidities like diabetes, arterial hypertension or co-morbidity factors such as hypercholesterolemia, obesity and body fat distribution as well as fat-rich diet and physical inactivity are common in elderly persons and are associated with higher risk of stroke, increased mortality and disability. Obesity could represent a state of chronic inflammation that can be prevented to some extent by non-pharmaceutical interventions such as calorie restriction and hypothermia.

Caloric restriction stabilizes body weight and accelerates behavioral recovery in aged rats after focal ischemia.

Obesity and hyperinsulinemia are risk factors for stroke. We tested the hypothesis that caloric restriction, which reduces the incidence of age-related obesity and metabolic syndrome, may represent an efficient and cost-effective strategy for preventing stroke and its devastating consequences. To this end, we placed aged, obese Sprague-Dawley aged rats on a calorie-restricted diet for 8 weeks prior to the experimental infarction.

Combining electrospinning and cell sheet technology for the development of a multiscale tissue engineered ligament construct (TELC).

Ligament tissue rupture is a common sport injury. Although current treatment modalities can achieve appropriate reconstruction of the damaged ligament, they present significant drawbacks, mostly related to reduced tissue availability and pain associated with tissue harvesting. Stem cell based tissue regeneration combined with electrospun scaffolds represents a novel treatment method for torn ligaments.

Artistic Skills Recovery and Compensation in Visual Artists after Stroke.

Background: Art is a characteristic of mankind, which requires superior central nervous processing and integration of motor functions with visual information. At the present time, a significant amount of information related to neurobiological basis of artistic creation has been derived from neuro-radiological cognitive studies, which have revealed that subsequent to tissue destruction, the artists continue to create art. The current study aims to review the most important cases of visual artists with stroke and to discuss artistic skills recovery and compensation as well as artistic style after stroke.

The effect of bisphosphonates on the endothelial differentiation of mesenchymal stem cells.

The contribution of the local stem cell niche to providing an adequate vascular framework during healing cannot be overemphasized. Bisphosphonates (BPs) are known to have a direct effect on the local vasculature, but their effect on progenitor cell differentiation is unknown. This in vitro study evaluated the effect(s) of various BPs on the differentiation of human placental mesenchymal stem cells (pMSCs) along the endothelial lineage and their subsequent functional and morphogenic capabilities.

Neuroinflammation and comorbidities are frequently ignored factors in CNS pathology.

Virtually all drug interventions that have been successful pre-clinically in experimental stroke have failed to prove their efficacy in a clinical setting. This could be partly explained by the complexity and heterogeneity of human diseases as well as the associated co-morbidities which may render neuroprotective drugs less efficacious in clinical practice. One aspect of crucial importance in the physiopathology of stroke which is not completely understood is neuroinflammation.

In vitro pre-vascularisation of tissue-engineered constructs A co-culture perspective.

In vitro pre-vascularization is one of the main vascularization strategies in the tissue engineering field. Culturing cells within a tissue-engineered construct (TEC) prior to implantation provides researchers with a greater degree of control over the fate of the cells. However, balancing the diverse range of different cell culture parameters in vitro is seldom easy and in most cases, especially in highly vascularized tissues, more than one cell type will reside within the cell culture system.

Standardization of negative controls in diagnostic immunohistochemistry: recommendations from the international ad hoc expert panel.

Standardization of controls, both positive and negative controls, is needed for diagnostic immunohistochemistry (dIHC). The use of IHC-negative controls, irrespective of type, although well established, is not standardized. As such, the relevance and applicability of negative controls continues to challenge both pathologists and laboratory budgets.

Dental implant placement with bone augmentation in a patient who received intravenous bisphosphonate treatment for osteoporosis.

Intravenous (IV) administration of bisphosphonates has been considered an absolute contraindication for placement of dental implants, because of the increased risk of bisphosphonate-related osteonecrosis of the jaw (BRONJ). However, the evidence regarding this association originates from patients being treated for various forms of metastatic cancer. In the case reported here, a patient received a dental implant while undergoing IV treatment with zoledronic acid for osteoporosis.

Bisphosphonate-related osteonecrosis of jaw (BRONJ): diagnostic criteria and possible pathogenic mechanisms of an unexpected anti-angiogenic side effect.

Recently, bisphosphonates (BPs) have been widely used in medical practice as anti-resorptive agents owing to their anti-osteoclatic action. In addition, these compounds are also used for their analgesic action and their potential anti-tumour effect. Patients treated with BPs may subsequently develop osteonecrosis of the jaw or maxillary bone after minor local trauma including dental work, recently labelled as bisphosphonate osteonecrosis of jaw (BRONJ).

Citicoline induces angiogenesis improving survival of vascular/human brain microvessel endothelial cells through pathways involving ERK1/2 and insulin receptor substrate-1.

Background: Citicoline is one of the neuroprotective agents that have been used as a therapy in stroke patients. There is limited published data describing the mechanisms through which it acts.

Methods: We used in vitro angiogenesis assays: migration, proliferation, differentiation into tube-like structures in Matrigel™ and spheroid development assays in human brain microvessel endothelial cells (hCMEC/D3).

Prostate carcinoma metastatic to the skin as an extrammamary Paget's disease.

Aim: The current paper describes a case of prostatic adenocarcinoma metastatic to the skin presenting as an extrammamary Paget's disease, a very rare and poorly characterised morphological entity. We report a case of prostatic carcinoma metastatic to skin showing a pattern of extramammary Paget's disease which has not been clearly illustrated in the literature Case presentation: A 63 year-old man with prostatic adenocarcinoma developed cutaneous metastases after 16 years. The inguinal metastases were sessile and 'keratotic.

Bisphosphonate-related osteonecrosis of jaw (BRONJ): an anti-angiogenic side-effect?

Bisphosphonates are recommended in the treatment of osteoporosis and some cancers, in which case they prevent the appearance of bone metastasis. The patients taking bisphosphonates are at increased risk of developing bisphosphonate-related osteonecrosis of jaw (BRONJ) which is characterised by the presence of an un-healing wound after dental surgery. BRONJ might represent an anti-angiogenic side effect.

Angiogenesis in old-aged subjects after ischemic stroke: a cautionary note for investigators.

Angiogenesis represents a form of neovascularisation of exceptional importance in numerous pathological conditions including stroke. In this context it is directly related to neuroregeneration which is seen in close proximity. However, numerous experimental data have been drawn from studies that have ignored the age criterion.

Mild systemic inflammation has a neuroprotective effect after stroke in rats.

Stroke is accompanied by a strong inflammatory reaction in the brain. Periodontal disease is a chronic local infection which causes a systemic low grade inflammation. We hypothesized that a mild systemic inflammatory reaction as caused by periodontal disease prior to stroke onset, may exert a neuroprotective effect in a rat model of focal ischemia.

Cellular and molecular events underlying the dysregulated response of the aged brain to stroke: a mini-review.

Background: Age-related brain injuries, including stroke, are a major cause of physical and mental disabilities.

Objective: Therefore, studying the basic mechanism underlying functional recovery after brain stroke in aged subjects is of considerable clinical interest.

Methods: This review summarizes the effects of age on recovery after stroke in an animal model, with emphasis on the underlying cellular mechanisms.

Placental calcium pump: clinical-based evidence.

Placenta can be considered as a pump of calcium necessary for the normal development of the fetus. We believe that the location of this pump is in the placental basement membrane. The calcification of this membrane has been described only in cases of in utero fetal death.