Potential Application of MicroRNAs and Some Other Molecular Biomarkers in Alzheimer's Disease.

Alzheimer's disease (AD) is the world's most common neurodegenerative disease, expected to affect up to one-third of the elderly population in the near future. Among the major challenges in combating AD are the inability to reverse the damage caused by the disease, expensive diagnostic tools, and the lack of specific markers for the early detection of AD. This paper highlights promising research directions for molecular markers in AD diagnosis, including the diagnostic potential of microRNAs. The latest molecular methods for diagnosing AD are discussed, with particular emphasis on diagnostic techniques prior to the appearance of full AD symptoms and markers detectable in human body fluids. A collection of recent studies demonstrates the promising potential of molecular methods in AD diagnosis, using miRNAs as biomarkers. Up- or downregulation in neurodegenerative diseases may not only provide a new diagnostic tool but also serve as a marker for differentiating neurodegenerative diseases. However, further research in this direction is needed.

Molecular Mechanisms in the Design of Novel Targeted Therapies for Neurodegenerative Diseases.

Neurodegenerative diseases are a diverse group of diseases characterized by a progressive loss of neurological function due to damage to nerve cells in the central nervous system. In recent years, there has been a worldwide increase in the expanding associated with increasing human life expectancy. Molecular mechanisms control many of the essential life processes of cells, such as replication, transcription, translation, protein synthesis and gene regulation. These are complex interactions that form the basis for understanding numerous processes in the organism and developing new diagnostic and therapeutic approaches. In the context of neurodegenerative diseases, molecular basis refers to changes at the molecular level that cause damage to or degeneration of nerve cells. These may include protein aggregates leading to pathological structures in brain cells, impaired protein transport in nerve cells, mitochondrial dysfunction, inflammatory processes or genetic mutations that impair nerve cell function. New medical therapies are based on these mechanisms and include gene therapies, reduction in inflammation and oxidative stress, and the use of miRNAs and regenerative medicine. The aim of this study was to bring together the current state of knowledge regarding selected neurodegenerative diseases, presenting the underlying molecular mechanisms involved, which could be potential targets for new forms of treatment.

Virus-Based Biological Systems as Next-Generation Carriers for the Therapy of Central Nervous System Diseases.

Central nervous system (CNS) diseases are currently a major challenge in medicine. One reason is the presence of the blood-brain barrier, which is a significant limitation for currently used medicinal substances that are characterized by a high molecular weight and a short half-life. Despite the application of nanotechnology, there is still the problem of targeting and the occurrence of systemic toxicity. Viral vectors and virus-like particles (VLPs) may provide a promising solution to these challenges. Their small size, biocompatibility, ability to carry medicinal substances, and specific targeting of neural cells make them useful in research when formulating a new generation of biological carriers. Additionally, the possibility of genetic modification has the potential for gene therapy. Among the most promising viral vectors are adeno-associated viruses, adenoviruses, and retroviruses. This is due to their natural tropism to neural cells, as well as the possibility of genetic and surface modification. Moreover, VLPs that are devoid of infectious genetic material in favor of increasing capacity are also leading the way for research on new drug delivery systems. The aim of this study is to review the most recent reports on the use of viral vectors and VLPs in the treatment of selected CNS diseases.

Effectiveness of plasmapheresis in ANCA clearance in patients with ANCA-associated vasculitides.

Introduction: Plasmapheresis is a therapeutic method based on removal of high molecular weight particles from blood. It is used in a variety of clinical entities in which pathogenic role of such particles has been proven e.g. ANCA-associated vasculitides (granulomatosis with polyangiitis [GPA] and microscopic polyangiitis [MPA]). Efficacy of plasmapheresis in ANCA antibodies removal and its impact on disease activity has not been adequately investigated so far. Influence of antibodies levels on disease activity also remains unknown. Objectives: Analysis of plasmapheresis effect on serum ANCA levels in patients with ANCA-associated vasculitides. Patients and methods: Seven patients with diagnoses of ANCA-associated vasculitides were enrolled in the study between November 2015 and April 2016. All of them underwent plasmapheresis procedures. Serum ANCA levels were measured before and after plasmaphereses using fluoroimmunoenzymatic assay (FEIA). Disease activity was assessed using Birmingham Activity Vasculitis Score; BVAS ver. 3 before first plasma exchange procedure. Results: Patients in disease exacerbation (BVAS 5-10) with positive ANCA antibodies were enrolled in the study: 2 patients with GPA and 5 patients with MPA. Number of performed plasmapheresis procedures ranged from 5 to 7 (median=7). Decrease of serum antibodies concentration was observed in all patients (mean decrease of 88.3% (±10.1%)) with statistically significant difference in mean antibodies concentration before and after plasmapheresis procedures (113.0 vs 15.4; p=0.014). Conclusions: Plasmapheresis is an effective method of ANCA antibodies removal in patients in disease exacerbation.

Continuous renal replacement therapy during extracorporeal membrane oxygenation in patients treated in medical intensive care unit: technical considerations.

Extracorporeal membrane oxygenation (ECMO) is used as a salvage therapy in refractory acute respiratory distress syndrome (ARDS). Although technological progress in the ECMO systems improved the survival rate, prognosis is still significantly worsened by acute kidney injury (AKI), particularly if renal replacement therapy (RRT) is required. There are no exact guidelines recommending which techniques of ECMO and continuous RRT (CRRT) should be used for management of AKI coexisting with respiratory or circulatory failure, and how to combine them. The aim of this review is to describe methods of CRRT and ECMO simultaneous application, and to present advantages of various technical approaches versus possible complications.

Supportive therapy for a patient with toxic epidermal necrolysis undergoing plasmapheresis.

A patient with severe toxic epidermal necrolysis underwent 2 cycles of therapeutic plasma exchange and received specialized wound care for widespread skin damage of more than 80% of his body surface area. Extensive involvement of mucous membranes, including the conjunctivas and the oropharyngeal cavity, and damage of his genitourinary organs required meticulous wound care. Daily care of injuries of tissues affected only in the most severe cases of toxic epidermal necrolysis was provided by an experienced intensive care unit nursing team. A meticulous supportive therapy regimen was a major contributing factor to this patient's remission.

Complications in patients treated with plasmapheresis in the intensive care unit.

INTRODUCTION: Plasmapheresis is one of the methods of extracorporeal blood purification involving the removal of inflammatory mediators and antibodies. The procedure is used in a variety of conditions, including autoimmune diseases. The aim of the present study was to analyse the incidence of plasmapheresis-related complications in patients treated in the intensive care unit (ICU). METHODS: The analysis involved 370 plasmapheresis procedures in 54 patients. The data were collected from patients' medical records, including procedure protocols. RESULTS: The most common diseases treated with plasmapheresis included: myasthenia gravis (33.3%), Guillain-Barre syndrome (14%), Lyell's syndrome (9.3%), systemic lupus erythematosus (7.4%), and thrombotic thromcytopenic purpura (7.4%). The adverse side effects observed most frequently during plasma filtration were: fall in arterial blood pressure (8.4% of all procedures), arrhythmias (3.5%), sensations of cold with temporarily elevated temperature and paresthesias (1.1%, each). In most cases the symptoms were mild and transient. Severe and life-threatening episodes, i.e. shock, fall in arterial blood pressure requiring pressor amines, persistent arrhythmias and haemolysis, developed in 2.16% of procedures. CONCLUSIONS: Plasmapheresis can be considered a relatively safe method of treatment of ICU patients. Continuous observation and proper monitoring of patients provided by highly trained medical personnel are essential for its safety.

[Plasmapheresis--possible complications and their prevention]. / Plazmafereza--mozliwe powiklania i ich zapobieganie.

Plasmapheresis it is a therapeutic method based on extracorporeal plasma exchange. First attempts at treatment with plasmapheresis date back to the beginning of the 20th century. However, it was first brought to clinical practice only in the 1950s as a way of treating Waldenstrom macroglobulinemia and in last decades a dynamic improvement in this method has been observed. At the moment plasmapheresis is used in the treatment of over 150 diseases. Like every invasive method, it may cause complications, which are due to anticoagulation, the use of replacement fluids, the technical part of the procedure, and the presence of intravenous catheters. The knowledge of potential complications and the way of preventing them by the medical staff help to avoid complications and to decrease their harmful effects.

Beneficial therapeutic effect of plasmapheresis after unsuccessful treatment with corticosteroids in two patients with severe toxic epidermal necrolysis.

Toxic epidermal necrolysis (TEN) is a rare, life-threatening disease with a high mortality rate. It is linked to drug toxicity and characterized by epidermal necrolysis with mucositis and conjunctivitis. Treatment is not established due to the unknown pathogenesis and lack of randomized clinical trials. It is mostly based on withdrawal of the culprit drug and symptom-related approach. The role of corticosteroids and plasmapheresis in the disease treatment remains controversial. We present two patients with severe TEN (both with >80% body skin surface involvement) treated unsuccessfully with corticosteroids followed by plasmapheresis. Plasmapheresis led to prompt improvement, with extensive reepithealization of the skin, and eventually total recovery of both patients. In severe TEN unresponsive to corticosteroids, treatment with plasmapheresis should be considered.

[Plasmapheresis in intensive therapy unit]. / Plazmafereza w oddziale intensywnej terapii.

Plasmapheresis or therapeutic plasma exchange is a procedure designed to deplete the body of blood plasma without blood cells. Whole blood is removed from the body, the plasma is separated from the cells, and the cells are suspended in saline before being returned to the patient. The procedure is used to remove excess antibodies, immunoglobulins, or cytokines from the blood in various clinical situations. The particles removed should be adequately large (>15 kDa) and have a relatively long half-life. The volume of removed plasma should be based on body weight and haematocrit, and in an adult patient be in range of 2.5-2.7 litres (30-40 mL kg(-1)). To remove 90% of a harmful substance, four to five exchanges are necessary. In the review, several modes of plasmapheresis are described. The most common indications for plasmapheresis in patients treated in an ITU are: thrombotic thrombocytopenic purpura, Waldenström macroglobulinemia, Guillain-Barre syndrome, chronic inflammatory poliradiculopathy, myasthenia gravis, or Lambert-Eaton syndrome.The procedure is safe, and complications are rare and not serious.