Adipobiology of obstructive sleep Apnea syndrome

Obstructive sleep apnea (OSA) syndrome has emerged as a major public health problem because of its high prevalence amongst middle-aged, obese men as well as in lean individuals and women. It has been suggested that obesity`s role in the genesis of sleep apnea is rather through its metabolic activity than a purely anatomic / mechanical impact. Recent studies demonstrate that circulating levels of adipocytes, adipose tissue-derived secretory proteins, are altered in patients with OSA syndrome. For in- stance, leptin level is increased, whereas that of adiponectin decreased in OSA, and these changes can be reversed by treatment of apnea/hypopnea episodes. Adipokine profile seems to change towards a pro inflammatory pattern that may also contribute to OSA-related cardio metabolic diseases. The mechanisms of adipose dysfunction in OSA includes hypoxia, oxidative stress and increased sympathetic nervous activity, including alterations in the circulating levels of the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). In effect, reversing hypoxia and attenuating oxidative stress and inflammation through adipokine and NGF/BDNF- targeted pharmacology may provide novel therapeutic opportunities in patients with OSA syndrome

Circulating irisin levels in newly diagnosed obstructive sleep apnea patients

Introduction: Obstructive sleep apnea syndrome (OSAS) is commonly associated with obesity, insulin resistance, metabolic syndrome, hypertension, and coronary artery disease. Irisin is a newly identified myokine and its serum concentration was found to be correlated with cardiac troponin and creatin kinase-MB in acute myocardial infarction patients. Furthermore, irisin levels were positively associated with endothelium-dependent vasodilation in type 2 diabetic patients.Aim: In this study, we aimed to investigate serum irisin level in the newly diagnosed OSAS patients.Materials and Methods: After obtaining ethical approval, 32 OSAS patients were included. All patients gave written informed consent. Diagnosis of OSAS was verified by an overnight polysomnography (PSG) and made by an apnea hypopnea index equal to or higher than 5. Venous blood samples were collected in the morning between 08.00 – 10.00 after PSG (n=25) or after one-night CPAP treatment (n=7). Serum irisin concentrations were studied by ELISA.Results and Conclusion: Serum irisin concentrations were significantly higher in newly diagnosed OSAS group than in OSAS group after one night of CPAP treatment (199.7±42.4 vs 159.7±18.3 ng/mL respectively; p<0.01). These results suggest that increased serum irisin levels can be reduced by CPAP treatment and elevated serum irisin levels may be due to increased respiratory muscle activity and body temperature.

Mesenchymal Stem Cells for Treatment of CNS Injury

Brain and spinal cord injuries present significant therapeutic challenges. The treatments available for these conditions are largely ineffective, partly due to limitations in directly targeting the therapeutic agents to sites of pathology within the central nervous system (CNS). The use of stem cells to treat these conditions presents a novel therapeutic strategy. A variety of stem cell treatments have been examined in animal models of CNS trauma. Many of these studies have used stem cells as a cell-replacement strategy. These investigations have also highlighted the significant limitations of this approach. Another potential strategy for stem cell therapy utilises stem cells as a delivery mechanism for therapeutic molecules. This review surveys the literature relevant to the potential of mesenchymal stem cells for delivery of therapeutic agents in CNS trauma in humans

How does Nogo receptor influence demyelination and remyelination in the context of multiple sclerosis?

Multiple sclerosis (MS) can progress with neurodegeneration as a consequence of chronic inflammatory mechanisms that drive neural cell loss and/or neuroaxonal dystrophy in the central nervous system. Immune-mediated mechanisms can accumulate myelin debris in the disease extracellular milieu during chronic-active demyelination that can limit neurorepair/plasticity and experimental evidence suggests that potentiated removal of myelin debris can promote neurorepair in models of MS. The myelin-associated inhibitory factors (MAIFs) are integral contributors to neurodegenerative processes in models of trauma and experimental MS-like disease that can be targeted to promote neurorepair. This review highlights the molecular and cellular mechanisms that drive neurodegeneration as a consequence of chronic-active inflammation and outlines plausible therapeutic approaches to antagonize the MAIFs during the evolution of neuroinflammatory lesions. Moreover, investigative lines for translation of targeted therapies against these myelin inhibitors are defined with an emphasis on the chief MAIF, Nogo-A, that may demonstrate clinical efficacy of neurorepair during progressive MS

Signal transduction pathways involved in inhibition of axonal regeneration after CNS injury

SCI and MS are devastating conditions of the CNS that propagate neurological dysfunction with poor long term prognoses. In the past few decades, much effort has gone in to understanding mechanisms of neuroinflammation, demyelination and neurodegeneration that combined, drive the neurological deterioration observed in patients. However, currently available treatments are only effective in a small percentage of sufferers. Therefore there is an urgent need for the discovery of new and more effective therapies to dramatically improve patients quality of life. In recent years, a body of research has shifted towards discovering therapies that modulate mechanisms of neurodegeneration rather than immunomodulation. It is now evident that recurring axonal injury and eventual failure in regenerative compensatory mechanisms in the CNS are the major causes of irreversible neurological deficit observed in SCI and MS. The role of MAIFs and their potent capacity to drive neurodegeneration in damaged axons has been convincingly presented in the literature. Nogo-A, which signals through the NgR1 complex on axons, has been deemed the most potent inhibitor of regeneration. The overall aim of this thesis was to investigate Nogo-A/NgR1 signalling and their downstream mediators in the context of neurodegeneration in SCI and in the animal model for MS, EAE. Furthermore, we explored the potential of therapeutic agents in reversing the affects of Nogo-A/NgR1 signalling in an attempt to hinder neurodegeneration in these models. The first part of this thesis assessed the deposition of Nogo-A and the ROCKII-dependent phosphorylation of its downstream mediator CRMP-2 in a mouse model of SCI with and without the therapeutic intervention of daily LIF administration following injury. LIF administration resulted in substantial improvements in functional locomotor recovery in treated animals. At the molecular level LIF treatment reduced Nogo-A deposition at the lesion site. Similarly, RhoA-GTP and PCRMP-2 molecules which negatively regulate the cytoskeleton showed diminished activity. In contrast, factors indicative of growth and regeneration such as Rac-1 and GAP-43 were elevated in animals receiving LIF. Therefore factors like LIF that limit Nogo-A deposition in the injured CNS could have therapeutic potential in SCI. The second part of this thesis, a time-course evaluation of neurodegeneration in the MOG-induced EAE model was carried out, with a particular focus on the modulation of CRMP-2 in disease progression. CRMP-2 expression reached maximum levels at peak stage of EAE, however, its expression was evident as early as pre-onset stage of ii disease. In addition, levels of PCRMP-2 was associated with and only activated in neurodegenerative axons. Furthermore, molecular transport of tubulin heterodimers by CRMP-2 to promote microtubule assembly was impeded. Moreover, therapeutic administration of the function blocking Nogo-A antibody in EAE animals reduced clinical severity and in parallel decreased PCRMP-2 expression. These data indicated that Nogo-A signalling could mediate axonal degeneration through post-translational modification of CRMP-2 by negatively regulating microtubule assembly. Therefore, in the third part of this thesis, a direct relationship between NgR1 signalling and CRMP-2 phosphorylation and their role in mediating axonal degeneration in the progression of EAE was investigated. The clinical severity was significantly reduced in ngr1-/- mice with EAE. Correspondingly, ROCKII-dependent CRMP-2 phosphorylation was also diminished at all time points. Furthermore CRMP-2 association with tubulin heterodimers was restored, allowing for positive microtubule assembly and therefore regeneration. Moreover, the immune capacity of naive and EAE-induced ngr-/- mice remained unchanged, signifying that the observed alleviation in disease severity is due to alterations in mechanisms related to axonal injury and not mechanisms of immunomodulation. Collectively, research conducted in this thesis describe a common mechanism of neurodegeneration that can be activated in both SCI and EAE. It was demonstrated that growth inhibition can be initiated by MAIFs such as Nogo-A through the NgR1 complex in axons. A direct consequence of this is the ROCKII-dependent phosphorylation of CRMP-2 which impedes CRMP-2 transport of tubulin, negatively regulating microtubule assembly. Of particular relevance is the capacity of the CNS to regenerate when this mechanism is hindered by way of therapeutic intervention. Therefore, it can be concluded that targeting the components of MAIF/NgR1 signalling following CNS injury may provide novel therapeutic avenues by which neurological decline observed in patients can be diminished

Signal transduction pathways involved in inhibition of axonal regeneration after CNS injury

SCI and MS are devastating conditions of the CNS that propagate neurological dysfunction with poor long term prognoses. In the past few decades, much effort has gone in to understanding mechanisms of neuroinflammation, demyelination and neurodegeneration that combined, drive the neurological deterioration observed in patients. However, currently available treatments are only effective in a small percentage of sufferers. Therefore there is an urgent need for the discovery of new and more effective therapies to dramatically improve patients quality of life. In recent years, a body of research has shifted towards discovering therapies that modulate mechanisms of neurodegeneration rather than immunomodulation. It is now evident that recurring axonal injury and eventual failure in regenerative compensatory mechanisms in the CNS are the major causes of irreversible neurological deficit observed in SCI and MS. The role of MAIFs and their potent capacity to drive neurodegeneration in damaged axons has been convincingly presented in the literature. Nogo-A, which signals through the NgR1 complex on axons, has been deemed the most potent inhibitor of regeneration. The overall aim of this thesis was to investigate Nogo-A/NgR1 signalling and their downstream mediators in the context of neurodegeneration in SCI and in the animal model for MS, EAE. Furthermore, we explored the potential of therapeutic agents in reversing the affects of Nogo-A/NgR1 signalling in an attempt to hinder neurodegeneration in these models. The first part of this thesis assessed the deposition of Nogo-A and the ROCKII-dependent phosphorylation of its downstream mediator CRMP-2 in a mouse model of SCI with and without the therapeutic intervention of daily LIF administration following injury. LIF administration resulted in substantial improvements in functional locomotor recovery in treated animals. At the molecular level LIF treatment reduced Nogo-A deposition at the lesion site. Similarly, RhoA-GTP and PCRMP-2 molecules which negatively regulate the cytoskeleton showed diminished activity. In contrast, factors indicative of growth and regeneration such as Rac-1 and GAP-43 were elevated in animals receiving LIF. Therefore factors like LIF that limit Nogo-A deposition in the injured CNS could have therapeutic potential in SCI. The second part of this thesis, a time-course evaluation of neurodegeneration in the MOG-induced EAE model was carried out, with a particular focus on the modulation of CRMP-2 in disease progression. CRMP-2 expression reached maximum levels at peak stage of EAE, however, its expression was evident as early as pre-onset stage of ii disease. In addition, levels of PCRMP-2 was associated with and only activated in neurodegenerative axons. Furthermore, molecular transport of tubulin heterodimers by CRMP-2 to promote microtubule assembly was impeded. Moreover, therapeutic administration of the function blocking Nogo-A antibody in EAE animals reduced clinical severity and in parallel decreased PCRMP-2 expression. These data indicated that Nogo-A signalling could mediate axonal degeneration through post-translational modification of CRMP-2 by negatively regulating microtubule assembly. Therefore, in the third part of this thesis, a direct relationship between NgR1 signalling and CRMP-2 phosphorylation and their role in mediating axonal degeneration in the progression of EAE was investigated. The clinical severity was significantly reduced in ngr1-/- mice with EAE. Correspondingly, ROCKII-dependent CRMP-2 phosphorylation was also diminished at all time points. Furthermore CRMP-2 association with tubulin heterodimers was restored, allowing for positive microtubule assembly and therefore regeneration. Moreover, the immune capacity of naive and EAE-induced ngr-/- mice remained unchanged, signifying that the observed alleviation in disease severity is due to alterations in mechanisms related to axonal injury and not mechanisms of immunomodulation. Collectively, research conducted in this thesis describe a common mechanism of neurodegeneration that can be activated in both SCI and EAE. It was demonstrated that growth inhibition can be initiated by MAIFs such as Nogo-A through the NgR1 complex in axons. A direct consequence of this is the ROCKII-dependent phosphorylation of CRMP-2 which impedes CRMP-2 transport of tubulin, negatively regulating microtubule assembly. Of particular relevance is the capacity of the CNS to regenerate when this mechanism is hindered by way of therapeutic intervention. Therefore, it can be concluded that targeting the components of MAIF/NgR1 signalling following CNS injury may provide novel therapeutic avenues by which neurological decline observed in patients can be diminished

Efficiency of marination liquids prepared with koruk (Vitis vinifera L.) on safety and some quality attributes of poultry meat

WOS: 000479021400039In this study, the effects of marination liquids (ML) prepared with koruk juice on safety and quality of poultry meat were investigated. Meat samples inoculated with Salmonella Typhimurium ((sic) 6 log CFU/g) were marinated with different concentrations of koruk juice at 4 degrees C for 1, 2 and 18 h. As a result of the process, the counts of S. Typhimurium on meat samples were reduced in the range of 0.113-3.476 log CFU/g. The most effective treatment in reducing the counts of S. Typhimurium was achieved by marination with ML1 (100% koruk juice) for 18 h. TMAB counts of uninoculated meat samples were determined under detection limits after marination with ML1 for all marination times. When the concentration of koruk juice were increased in ML, TMAB count, pH value and cooking loss of marinated meat samples were decreased. After marination, L*, a* and b* values of meat samples were also increased. The samples marinated with ML3 (50% koruk juice + 50% water) and Cl (100% olive oil) for 18 h were the most favored samples in terms of general appreciation. The present results indicated that koruk juice could be used as alternative ML to improve the safety and quality of poultry meat.Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [TUBITAK-2209A]The authors are grateful for the financial support provided by the Scientific and Technological Research Council of Turkey (TUBITAK) for the project entitled "Inactivation effect of marination solutions prepared by koruk juice against Salmonella Typhimurium inoculated on poultry meat" under the project type TUBITAK-2209A

Peripheral osteoma of mandibular angulus: Analysis of the literature and report of a new case

Osteoma is a benign osteogenic neoplasm originating from the continuous proliferation of compact and/or cancellous mature bone. The tumor can be classified as peripheral, central or extra-skeletal regarding location and it commonly seen in the cranio-facial region especially at the skull and paranasal sinuses. The exact etiology of the tumor is still controversial; however, it is considered that infection, trauma, muscle activity contributes the occurrence of the tumor. Due to the slow growing nature of osteoma, it is coincidentally detected on radiographs or when the tumor reaches a large size enough to trigger symptoms and cause facial disfigurement. Although mainly detected in the craniofacial bones, osteomas are rarely located in the jaw bones.  The purpose of this review, is to present the diagnosis and treatment plan of a peripheral osteoma in the mandibular angulus region of an 8-year-old boy together with a review of published cases of peripheral osteomas of mandibular angulus.El osteoma es una neoplasia osteogénica benigna que se origina de la proliferación continua de hueso maduro compacto y/o esponjoso. El tumor se puede clasificar como periférico, central o extraesquelético con respecto a la ubicación y se ve comúnmente en la región craneofacial, especialmente en el cráneo y los senos paranasales. La etiología exacta del tumor sigue siendo controvertida; sin embargo, se considera que la infección, el trauma y la actividad muscular contribuyen a la aparición del tumor. Debido a la naturaleza de crecimiento lento del osteoma, se detecta casualmente en las radiografías o cuando el tumor alcanza un tamaño grande lo suficiente como para desencadenar síntomas y causar desfiguración facial. Aunque se detecta principalmente en los huesos craneofaciales, los osteomas rara vez se localizan en los huesos de la mandíbula. El objetivo de esta revisión es presentar el diagnóstico y el plan de tratamiento de un osteoma periférico en la región angular mandibular de un niño de 8 años junto con una revisión de casos publicados de osteomas periféricos de angulación mandibular

Evaluation of oxidative events and copper accumulatıon in oral tissues of patients wıth Wilson's disease: three case report.

Wilson's disease (WD), also known as hepatolenticular degeneration, was first described in 1912 by Kinnear Wilson. It is an autosomal recessive disorder caused by mutations in the ATP7B gene, a membrane-bound copper transporting ATPase. The disorder is caused by impairment of the copper transporting ATPase, ATP7B, in the liver, which disturbs copper transport, excretion into the bile, and incorporation into apoceruloplasmin. WD is an inherited copper metabolism disorder with pathological copper accumulation in many tissues, but especially in brain and liver. We conducted this study because copper accumulation in oral tissues in patients with WD have not been studied before. We think that copper accumulation and differences of oxidative events in oral tissues can cause tendency to periodontal diseases