What is the place of sclerostin in chronic kidney disease,atherosclerosis, and ageing?

International Urology and Nephrology -     

Harmful at non-cytotoxic concentrations: SiO2-SPIONs affect surfactant metabolism and lamellar body biogenesis in A549 human alveolar epithelial cells

The pulmonary delivery of nanoparticles (NPs) is a promising approach in nanomedicine. For the efficient and safe use of inhalable NPs, understanding of NP interference with lung surfactant metabolism is needed. Lung surfactant is predominantly a phospholipid substance, synthesized in alveolar type II cells (ATII), where it is packed in special organelles, lamellar bodies (LBs). In vitro and in vivo studies have reported NPs impact on surfactant homeostasis, but this phenomenon has not yet been sufficiently examined. We showed that in ATII-like A549 human lung cancer cells, silica-coated superparamagnetic iron oxide NPs (SiO₂-SPIONs), which have a high potential in medicine, caused an increased cellular amount of acid organelles and phospholipids. In SiO₂-SPION treated cells, we observed elevated cellular quantity of multivesicular bodies (MVBs), organelles involved in LB biogenesis. In spite of the results indicating increased surfactant production, the cellular quantity of LBs was surprisingly diminished and the majority of the remaining LBs were filled with SiO₂-SPIONs. Additionally, LBs were detected inside abundant autophagic vacuoles (AVs) and obviously destined for degradation. We also observed time- and dose-dependent changes in mRNA expression for proteins involved in lipid metabolism. Our results demonstrate that non-cytotoxic concentrations of SiO₂-SPIONs interfere with surfactant metabolism and LB biogenesis, leading to disturbed ability to reduce hypophase surface tension. To ensure the safe use of NPs for pulmonary delivery, we propose that potential NP interference with LB biogenesis is obligatorily taken into account.     

Cardiac Involvement in Fabry Disease: JACC Review Topic of the Week

Fabry disease (FD) is a rare X-linked inherited lysosomal storage disorder caused by deficient α-galactosidase A activity that leads to an accumulation of globotriasylceramide (Gb3) in affected tissues, including the heart. Cardiovascular involvement usually manifests as left ventricular hypertrophy, myocardial fibrosis, heart failure, and arrhythmias, which limit quality of life and represent the most common causes of death. Following the introduction of enzyme replacement therapy, early diagnosis and treatment have become essential to slow disease progression and prevent major cardiac complications. Recent advances in the understanding of FD pathophysiology suggest that in addition to Gb3 accumulation, other mechanisms contribute to the development of Fabry cardiomyopathy. Progress in imaging techniques have improved diagnosis and staging of FD-related cardiac disease, suggesting a central role for myocardial inflammation and setting the stage for further research. In addition, with the recent approval of oral chaperone therapy and new treatment developments, the FD-specific treatment landscape is rapidly evolving.     

Prevalence of FA-D2 Rare Complementation Group of Fanconi Anemia in Serbia

Objective

To investigate genetic subtypes of inherited bone marrow failure syndrome Fanconi anemia (FA) in Sebia. FA-D2 subtype was found to be the most frequent genetic subtype among investigated FA patients; specific observations of FA-D2 phenotype are pointed out.

Methods

Several biological endpoints of FA cells in vitro such as radiation-induced level of lymphocyte micronuclei (radiosensitivity), base line and radiation induced level of the DNA double strand breaks (DSBs), leukocyte apoptosis, and telomere capping function were assessed.

Results

The results indicate that all FA-D2 patients display radioresistant in vitro response, which is seen as significantly reduced yield of radiation-induced micronuclei. On the contrary, FA-A patients display radiosensitive in vitro response seen as increased number of radiation-induced micronuclei (MN). A massive elimination of irradiated cells via apoptosis is found in both FA-A and FA-D2 subtypes. In FA-A subtype apoptosis positively relates with the yield of radiation-induced MN, whereas in FA-D2 subtype apoptosis relates with a high percentage of cells carrying dysfunctional telomeres. The present results unequivocally demonstrate that cytokinesis-block micronucleus (CBMN) assay and analyses of telomere capping function can be used to distinguish FA-D2 and FA-A complementation groups.

Conclusions

Considering all biological endpoints were analyzed, it can be concluded that all FA patients are radiosensitive, regardless of their complementation group. Thus, using CBMN test and telomere capping function analysis can discriminate FA-A from FA-D2 complementation groups, which could be important for assessment the conditioning regimens prior to bone marrow transplantation.     

National Athletic Trainers' Association Position Statement: Preparticipation Physical Examinations and Disqualifying Conditions

Objective

To present athletic trainers with recommendations for the content and administration of the preparticipation physical examination (PPE) as well as considerations for determining safe participation in sports and identifying disqualifying conditions.

Background

Preparticipation physical examinations have been used routinely for nearly 40 years. However, considerable debate exists as to their efficacy due to the lack of standardization in the process and the lack of conformity in the information that is gathered. With the continuing rise in sports participation at all levels and the growing number of reported cases of sudden death in organized athletics, the sports medicine community should consider adopting a standardized process for conducting the PPE to protect all parties.

Recommendations

Recommendations are provided to equip the sports medicine community with the tools necessary to conduct the PPE as effectively and efficiently as possible using available scientific evidence and best practices. In addition, the recommendations will help clinicians identify those conditions that may threaten the health and safety of participants in organized sports, may require further evaluation and intervention, or may result in potential disqualification.Key Words: medical history, family history, sudden cardiac death, concussion, sickle cell trait, diabetes, heat illness, hydrationParticipation in organized US athletics continues to rise. During the 2010–2011 academic year, more than 7.6 million high school students took part in organized interscholastic sports, compared with 7.1 million in 2005–2006.¹ Similarly, an additional 444 077 National Collegiate Athletic Association student–athletes participated in intercollegiate athletics in 2010–2011, compared with 393 509 in 2005–2006.² This growth in participation has led to a concomitant rise in sudden death. Most sudden deaths have been attributed to congenital or acquired cardiovascular malformations involving male football and basketball players.^3–5 Other causes of sudden death include heat stroke, cerebral aneurysm, asthma, commotio cordis, and sickle cell trait.^4,5 As sports participation continues to increase and catastrophic death in athletes receives more attention, the medical community should consider adopting a standardized preparticipation examination (PPE) instrument that, at a minimum and to the extent possible, sets out to ensure a safe playing environment for all and to identify those conditions that might predispose an athlete to injury or sudden death.For nearly 4 decades, PPE screening has been used routinely in an attempt to identify those conditions that may place an athlete at increased risk and affect safe participation in organized sports. Few would empirically argue the potential benefits of this practice, yet considerable debate exists as to the current efficacy of the PPE, given the significant disparities that presently characterize the examination and the information gathered. Over time, the PPE has become an integral component of athletics and sports medicine programs; however, the lack of standardization in the process has created confusion. In addition, the failure to adequately define the primary objectives of the PPE has led to the consensus that, in its current form, the PPE does not address the ultimate goal of protecting the health and safety of the player.The American Medical Association Group on Science and Technology⁶ has asserted that every physician has 2 responsibilities to an athlete during the PPE: “(1) to identify those athletes who have medical conditions that place them at substantial risk for injury or sudden death and to disqualify them from participation or ensure they receive adequate medical treatment before participation and (2) to not disqualify athletes unless there is a compelling medical reason.” As the PPE has evolved over the years, it has become increasingly difficult to meet these standards given the many objectives that have been proposed for the screening instrument. Originally, the primary objectives of the PPE were to (1) detect life-threatening or disabling conditions, (2) identify those conditions that predispose the athlete to injury or disability, and (3) address legal and insurance requirements.^7,8 Today, however, those entities charged with developing and revising the PPE (eg, state high school athletic associations, medical associations, state education departments, state health departments, legislators)⁹ often have different missions, and as a result, they have sought to influence the makeup of the PPE to address their specific interests. This has led to the identification of a number of secondary objectives, including but not limited to documenting athletic eligibility, obtaining parental consent for participation and emergency treatment, and improving athlete performance.⁹ Most notably, the PPE represents the sole source of medical evaluation for 30% to 88% of children and adolescents annually^10,11 and an opportunity to identify conditions that, although not necessarily related to or requiring restriction from athletic participation, nonetheless call for additional follow-up.⁹ Some authors¹² have advocated this practice to evaluate the general health of the athlete and to provide an opening to discuss high-risk behaviors, preventive care measures, and nonathletic concerns. Others oppose this view, stating that the PPE “should not be the sole component of health care for athletes”⁶ and that the PPE can only be effective if the goals remain specific and properly directed toward the demands of sport participation.^6,13     

Nitroglycerine effects on portal vein mechanics and oxidative stress in portal hypertension

AIM:Тo examine the effects of nitroglycerine on portal vein haemodynamics and oxidative stress in patients with portal hypertension.METHODS:Thirty healthy controls and 39 patients with clinically verified portal hypertension and increasedvascular resistance participated in the study.Liver di-ameters,portal diameters and portal flow velocities were recorded using color flow imaging/pulsed Doppler detection.Cross-section area,portal flow and index of vascular resistance were calculated.In collected blood samples,superoxide anion radical (O 2-),hydrogen per-oxide (H 2 O 2),index of lipid peroxidation (measured as TBARS) and nitric oxide (NO) as a marker of endothelial response (measured as nitrite-NO 2-) were determined.Time-dependent analysis was performed at basal state and in 10th and 15th min after nitroglycerine (sublingual 0.5 mg) administration.RESULTS:Oxidative stress parameters changed sig-nificantly during the study.H 2 O 2 decreased at the end of study,probably via O 2-mediated disassembling in Haber Weiss and Fenton reaction;O 2-increased signifi-cantly probably due to increased diameter and tension and decreased shear rate level.Consequently O 2-and H 2 O 2 degradation products,like hydroxyl radical,initi-ated lipid peroxidation.Increased blood flow was to some extent lower in patients than in controls due to double paradoxes,flow velocity decreased,shear rate decreased significantly indicating non Newtonian char-acteristics of portal blood flow.CONCLUSION:This pilot study could be a starting point for further investigation and possible implemen-tation of some antioxidants in the treatment of portal hypertension.