Dose-Ranging Effects of the Intracerebral Administration of Atsttrin in Experimental Model of Parkinson's Disease Induced by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in Mice.

Parkinson's disease is one of the most common neurodegenerative disorders characterized by a multitude of motor and non-motor clinical symptoms resulting from the progressive and long-lasting abnormal loss of nigrostriatal dopaminergic neurons. Currently, the available treatments for patients with Parkinson's disease are limited and exert only symptomatic effects, without adequate signs of delaying or stopping the progression of the disease. Atsttrin constitutes the bioengineered protein which ultrastructure is based on the polypeptide chain frame of the progranulin (PGRN), which exerts anti-inflammatory effects through the inhibition of TNFα. The conducted preclinical studies suggest that the therapeutic implementation of Atsttrin may be potentially effective in the treatment of neurodegenerative diseases that are associated with the occurrence of neuroinflammatory processes. The aim of the proposed study was to investigate the effect of direct bilateral intracerebral administration of Atsttrin using stereotactic methods in the preclinical C57BL/6 mouse model of Parkinson's disease inducted by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication. The analysis of the dose dependency effects of the increasing doses of Atsttrin has covered a number of parameters and markers regarding neurodegenerative processes and inflammatory responses including IL-1α, TNFα, IL-6, TH, and TG2 mRNA expressions. Accordingly, the evaluation of the changes in the neurochemical profile included DA, DOPAC, 3-MT, HVA, NA, MHPG, 5-HT, and 5-HIAA concentration levels. The intracerebral administration of Atsttrin into the striatum effectively attenuated the neuroinflammatory reaction in evaluated neuroanatomical structures. Furthermore, the partial restoration of monoamine content and its metabolic turnover were observed. In this case, taking into account the previously described pharmacokinetic profile and extrapolated bioavailability as well as the stability characteristics of Atsttrin, an attempt was made to describe as precisely as possible the quantitative and qualitative effects of increasing doses of the compound within the brain tissue microenvironment in the presented preclinical model of the disease. Collectively, this findings demonstrated that the intracerebral administration of Atsttrin may represent a potential novel therapeutic method for the treatment of Parkinson's disease.

The Role of Rosavin in the Pathophysiology of Bone Metabolism.

Rosavin, a phenylpropanoid in Rhodiola rosea's rhizome, and an adaptogen, is known for enhancing the body's response to environmental stress. It significantly affects cellular metabolism in health and many diseases, particularly influencing bone tissue metabolism. In vitro, rosavin inhibits osteoclastogenesis, disrupts F-actin ring formation, and reduces the expression of osteoclastogenesis-related genes such as cathepsin K, calcitonin receptor (CTR), tumor necrosis factor receptor-associated factor 6 (TRAF6), tartrate-resistant acid phosphatase (TRAP), and matrix metallopeptidase 9 (MMP-9). It also impedes the nuclear factor of activated T-cell cytoplasmic 1 (NFATc1), c-Fos, the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and mitogen-activated protein kinase (MAPK) signaling pathways and blocks phosphorylation processes crucial for bone resorption. Moreover, rosavin promotes osteogenesis and osteoblast differentiation and increases mouse runt-related transcription factor 2 (Runx2) and osteocalcin (OCN) expression. In vivo studies show its effectiveness in enhancing bone mineral density (BMD) in postmenopausal osteoporosis (PMOP) mice, restraining osteoclast maturation, and increasing the active osteoblast percentage in bone tissue. It modulates mRNA expressions by increasing eukaryotic translation elongation factor 2 (EEF2) and decreasing histone deacetylase 1 (HDAC1), thereby activating osteoprotective epigenetic mechanisms, and alters many serum markers, including decreasing cross-linked C-telopeptide of type I collagen (CTX-1), tartrate-resistant acid phosphatase 5b (TRACP5b), receptor activator for nuclear factor κ B ligand (RANKL), macrophage-colony-stimulating factor (M-CSF), and TRAP, while increasing alkaline phosphatase (ALP) and OCN. Additionally, when combined with zinc and probiotics, it reduces pro-osteoporotic matrix metallopeptidase 3 (MMP-3), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α), and enhances anti-osteoporotic interleukin 10 (IL-10) and tissue inhibitor of metalloproteinase 3 (TIMP3) expressions. This paper aims to systematically review rosavin's impact on bone tissue metabolism, exploring its potential in osteoporosis prevention and treatment, and suggesting future research directions.

The Role of Progranulin (PGRN) in the Pathogenesis of Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) represents the most common and aggressive malignant form of brain tumour in adults and is characterized by an extremely poor prognosis with dismal survival rates. Currently, expanding concepts concerning the pathophysiology of GBM are inextricably linked with neuroinflammatory phenomena. On account of this fact, the identification of novel pathomechanisms targeting neuroinflammation seems to be crucial in terms of yielding successful individual therapeutic strategies. In recent years, the pleiotropic growth factor progranulin (PGRN) has attracted significant attention in the neuroscience and oncological community regarding its neuroimmunomodulatory and oncogenic functions. This review of the literature summarizes and updates contemporary knowledge about PGRN, its associated receptors and signalling pathway involvement in GBM pathogenesis, indicating possible cellular and molecular mechanisms with potential diagnostic, prognostic and therapeutic targets in order to yield successful individual therapeutic strategies. After a review of the literature, we found that there are possible PGRN-targeted therapeutic approaches for implementation in GBM treatment algorithms both in preclinical and future clinical studies. Furthermore, PGRN-targeted therapies exerted their highest efficacy in combination with other established chemotherapeutic agents, such as temozolomide. The results of the analysis suggested that the possible implementation of routine determinations of PGRN and its associated receptors in tumour tissue and biofluids could serve as a diagnostic and prognostic biomarker of GBM. Furthermore, promising preclinical applications of PGRN-related findings should be investigated in clinical studies in order to create new diagnostic and therapeutic algorithms for GBM treatment.

Fracture of the Lumbar Spine Associated with Ureteral Injury Mimicking Spondylodiscitis Followed by Cervical Spine Fracture in Patient with Ankylosing Hyperostosis.

The purpose of this case report is to describe the case of a patient with ankylosing spinal hyperostosis (ASH) and lumbar spine fracture complicated by ureteral injury mimicking spondylodiscitis with osteomyelitis features and retroperitoneal abscess formation followed by the cervical spine fracture. A consecutive analysis and summary of the medical history, radiological documentation, operative procedure, complications, and outcomes were performed. A 59-year-old man presented with abdominal pain three weeks after sustaining a low-energy fall. The performed CT scans demonstrated a three-column fracture at the L3/L4 level and features of ASH. Additionally, MRI scans demonstrated hyperintense fluid collection within L3/L4 intervertebral space communicating with both psoas major muscles, mimicking spondylodiscitis with osteomyelitis features and retroperitoneal abscess formation. An in situ instrumented lumbar fusion at the L2-L3-L5-S1 levels with implantation vertebral body replacement implant at the L3/L4 level was performed. Postoperative CT imaging revealed evidence of post-traumatic right ureteral injury. Following urological treatment covering nephrectomy and ureter ligation, the patient was maintained at a 2-year follow-up. After this period, the patient presented again with tetraparesis after sustaining a low-energy fall. The performed CT scans demonstrated a three-column fracture at the C5/C6 level. The combined anterior and posterior osteosynthesis at the C4-C5-C6-C7 levels was performed. This case report presents the rare clinical constellation regarding the lumbar spine fracture complicated by ureteral injury followed by a cervical spine fracture regarding the same patient. The potential injury of retroperitoneal structures, including the ureter after hyperextensive lumbar spine fracture, should be considered in ASH patients. In this case, one should be aware of the atypical clinical presentation regarding the observed spondylodiscitis- and osteomyelitis-like features.

The Role of Progranulin (PGRN) in the Pathogenesis of Ischemic Stroke.

Stroke is a life-threatening medical condition and is a leading cause of disability. Cerebral ischemia is characterized by a distinct inflammatory response starting with the production of various cytokines and other inflammation-related agents. Progranulin (PGRN), a multifunctional protein, is critical in diverse physiological reactions, such as cell proliferation, inflammation, wound healing, and nervous system development. A mature PGRN is anti-inflammatory, while granulin, its derivative, conversely induces pro-inflammatory cytokine expression. PGRN is significantly involved in the brain tissue and its damage, for example, improving mood and cognitive disorders caused by cerebral ischemia. It may also have protective effects against nerve and spinal cord injuries by inhibiting neuroinflammatory response and apoptosis or it may be related to the proliferation, accumulation, differentiation, and activation of microglia. PGRN is a neurotrophic factor in the central nervous system. It may increase post-stroke neurogenesis of the subventricular zone (SVZ), which is particularly important in improving long-term brain function following cerebral ischemia. The neurogenesis enhanced via PGRN in the ischemic brain SVZ may be attributed to the induction of PI3K/AKT and MAPK/ERK signaling routes. PGRN can also promote the proliferation of neural stem/progenitor cells through PI3K/AKT signaling pathway. PGRN increases hippocampal neurogenesis, reducing anxiety and impaired spatial learning post-cerebral ischemia. PGRN alleviates cerebral ischemia/reperfusion injury by reducing endoplasmic reticulum stress and suppressing the NF-κB signaling pathway. PGRN can be introduced as a potent neuroprotective agent capable of improving post-ischemia neuronal actions, mainly by reducing and elevating the inflammatory and anti-inflammatory cytokines. Expression, storage, cleavage, and function of progranulin (PGRN) in the pathogenesis of ischemic stroke.

Post-mortem detection of neuronal and astroglial biochemical markers in serum and urine for diagnostics of traumatic brain injury.

Currently available epidemiological data shows that traumatic brain injury (TBI) represents one of the leading causes of death that is associated with medico-legal practice, including forensic autopsy, criminological investigation, and neuropathological examination. Attention focused on TBI research is needed to advance its diagnostics in ante- and post-mortem cases with regard to identification and validation of novel biomarkers. Recently, several markers of neuronal, astroglial, and axonal injury have been explored in various biofluids to assess the clinical origin, progression, severity, and prognosis of TBI. Despite clinical usefulness, understanding their diagnostic accuracy could also potentially help translate them either into forensic or medico-legal practice, or both. The aim of this study was to evaluate post-mortem pro-BDNF, NSE, UCHL1, GFAP, S100B, SPTAN1, NFL, MAPT, and MBP levels in serum and urine in TBI cases. The study was performed using cases (n = 40) of fatal head injury and control cases (n = 20) of sudden death. Serum and urine were collected within ∼ 24 h after death and compared using ELISA test. In our study, we observed the elevated concentration levels of GFAP and MAPT in both serum and urine, elevated concentration levels of S100B and SPTAN1 in serum, and decreased concentration levels of pro-BDNF in serum compared to the control group. The obtained results anticipate the possible implementation of performed assays as an interesting tool for forensic and medico-legal investigations regarding TBI diagnosis where the head injury was not supposed to be the direct cause of death.

Progranulin (PGRN) as a regulator of inflammation and a critical factor in the immunopathogenesis of cardiovascular diseases.

Immune dysregulation has been identified as a critical cause of the most common types of cardiovascular diseases (CVDs). Notably, the innate and adaptive immune responses under physiological conditions are typically regulated with high sensitivity to avoid the exacerbation of inflammation, but any dysregulation can probably be associated with CVDs. In this respect, progranulin (PGRN) serves as one of the main components of the regulation of inflammatory processes, which significantly contributes to the immunopathogenesis of such disorders. PGRN has been introduced among the secreted growth factors as one related to wound healing, inflammation, and human embryonic development, as well as a wide variety of autoimmune diseases. The relationship between the serum PGRN and TNF-α ratio with the spontaneous bacterial peritonitis constitute one of the independent predictors of these conditions. The full-length PGRN can thus effectively reduce the calcification of valve interstitial cells, and the granulin precursor (GRN), among the degradation products of PGRN, can be beneficial. Moreover, it was observed that, PGRN protects the heart against ischemia-reperfusion injury. Above all, PGRN also provides protection in the initial phase following myocardial ischemia-reperfusion injury. The protective impact of PGRN on this may be associated with the early activation of the PI3K/Akt signaling pathway. PGRN also acts as a protective factor in hyperhomocysteinemia, probably by down-regulating the wingless-related integration site Wnt/ß-catenin signaling pathway. Many studies have further demonstrated that SARS-CoV-2 (COVID-19) has dramatically increased the risks of CVDs due to inflammation, so PGRN has drawn much more attention among scholars. Lysosomes play a pivotal role in the inflammation process, and PGRN is one of the key regulators in their functioning, which contributes to the immunomodulatory mechanism in the pathogenesis of CVDs. Therefore, investigation of PGRN actions can help find new prospects in the treatment of CVDs. This review aims to summarize the role of PGRN in the immunopathogenesis of CVD, with an emphasis on its treatment.

The impact of changing the funding model for genetic diagnostics and improved access to personalized medicine in oncology.

AIM: In January 2017, a new funding model for diagnostic genetic testing in cancer was introduced in Poland. OBJECTIVES: The aim of this study was to assess the impact of changing the funding model for genetic diagnosis in oncology on improving access to personalized medicine in Poland between 2017 and 2019. METHODS: The analysis included data on settlements with the National Health Fund for genetic tests in cancer under a contract of the hospital treatment type and under the contract in the type of separately contracted services between 2017 and 2019. RESULTS: The 150,647 diagnostic genetic tests were reported, which were billed to 111,872 patients. The average number of tests per patient was 1.35. One test was billed to 83.5% of patients, 11.2% of patients had two tests billed, and 5.3% had at least three tests billed. The number of services provided under the hospital treatment contract in 2018 doubled compared to the previous year. For separately contracted services, more than threefold increase in genetic testing performed in 2019 compared to 2018 was observed. CONCLUSION: our data show that the novel funding model for genetic services introduced in Poland has positive impact on the availability of genetic testing for patients.

Omega-3 fatty acids in the treatment of spinal cord injury: untapped potential for therapeutic intervention?

Omega-3 fatty acids constitute a group of fatty acids with anti-inflammatory and preventive effects against various diseases. Studies in animal models have demonstrated the preventive and therapeutic effects of omega-3 fatty acids after spinal cord injury (SCI) in reducing inflammatory reactions and promoting neuroregeneration. However, studies on the efficacy of omega-3 fatty acids in treatment and prevention after SCI seem to be questionable. This study evaluates potential reasons for omega-3 fatty acid therapy oversight in populations after SCI. Therefore, some of the reasons could cover heterogeneous patient groups in size, level of injury, quality of life assessment, time since injury, no single standardised dose, various follow-up durations and metabolic changes, often insufficient to record. Due to the difficulty of collecting cases for the study, especially in the acute phase after SCI, multicenter, coordinated studies are needed to establish the effects of omega-3 fatty acids on treatment, recovery, and disease prevention in patients after SCI. Although the present results of such studies are still inconclusive, the failure to exploit the potential properties of omega-3 fatty acids in the treatment of patients with SCI solely due to methodological difficulties should be considered a potential waste.

The role of inflammatory mediators in the pathogenesis of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome.

INTRODUCTION: As a recurrent disease, periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is characterized by episodes of febrile attacks and is often prominent in children under five years of age. However, the etiology of this condition has not been fully understood yet. MATERIALS AND METHODS: The search in the extensive literature of peer-reviewed articles published from the inception to December 2021 was conducted to identify the relevant studies, using the electronic databases of MEDLINE/PubMed, Embase, Scopus, the Cochrane Library, and the Web of Science. RESULTS: The analysis of complex relationships indicates that inflammatory factors, such as various cytokines and acute-phase proteins (APPs), play leading roles in the pathogenesis of this disease. Accordingly, this article summarizes the current state of knowledge to explain the mechanisms involved in inflammatory responses among patients with PFAPA syndrome and investigate its role in the pathogenesis of this disease. Moreover, the possibilities for further implementation of new therapeutic strategies are pointed out. CONCLUSION: It is concluded that some pathophysiological processes are associated with immune dysregulation, which itself may be secondary to environmental factors, genetic background, and underlying diseases, including latent infections that multiply inflammatory mediators. elevated inflammatory markers similarly play a significant part in the clinical outcomes of this condition, whose pyrogenic nature is the reason for the development of episodes of febrile attacks in the population of patients suffering from PFAPA syndrome.

Involvement of progranulin (PGRN) in the pathogenesis and prognosis of breast cancer.

Breast cancer constitute a common type of oncological disease with a highlighted mortality rate. In recent years, researchers have introduced progranulin (PGRN) as an novel potential biomarker and associated its function with higher risk factor for development of breast cancer. The present review article collects evidence on the association of PGRN with clinicopathological features and drug resistance in the patients with breast cancer. The results of this study suggested the use of routine determination of PGRN in the clinic as a reliable biomarker for screening people at high risk or as early indication of breast cancer. Targeting PGRN and its associated signaling pathways and receptors, such as sortilin (SORT1), could also cover a novel therapeutic strategy in the breast cancer.

Elevated serum and urine levels of progranulin (PGRN) as a predictor of microglia activation in the early phase of traumatic brain injury: a further link with the development of neurodegenerative diseases.

Traumatic brain injury (TBI) is a frequent finding during forensic autopsies and neuropathological examinations in medico-legal practices. Despite the unprecedented attention currently focused on TBI pathogenesis, there is a need to improve its diagnostics through the use of novel biomarkers to facilitate detection, treatment, and prognosis. Recently, growth factor progranulin (PGRN) has attracted significant attention because of its neurotrophic and anti-inflammatory activities. The role of PGRN in TBI has not been widely discussed, although PGRN-related neuroinflammatory and neurodegenerative phenomena have been described. The aim of this study was to identify PGRN concentration levels in biofluids and examine PGRN and CD68 protein expression in brain tissue using immunohistochemical staining in individuals with fatal TBI in its early phase. The study was performed using cases (n = 30) of fatal head injury and control cases (n = 30) of sudden death. The serum and urine were collected within ~24 h after death and compared using the ELISA test, where brain specimens were stained with anti-PGRN and anti-CD68 antibodies. In our study, we observed elevated concentration levels of PGRN in the serum and urine of TBI individuals in the early phase of TBI. These changes were accompanied by increased expression of PGRN in the frontal cortex (1st-3rd layers), in which anti-CD68 immunostaining revealed disseminated cortical microglia activation. The possible implementation of performing such assays offers a novel and interesting tool for investigation and research regarding TBI diagnosis and pathogenesis. Furthermore, the above-mentioned surrogate biofluid assays may be useful in clinical prognosis and risk calculation of non-fatal cases of TBI, considering the development of neurodegenerative conditions of TBI individuals.

Kinetics of serum brain-derived neurotrophic factor (BDNF) concentration levels in epileptic patients after generalized tonic-clonic seizures.

OBJECTIVE: Epilepsy is a chronic neurological disorder characterized by the periodic and unpredictable occurrence of seizures. The serum level of brain-derived neurotrophic factor (BDNF) has been suggested to be a potential biomarker that could detect differences in epilepsy patients. Although there is considerable neurobiological evidence linking BDNF to epilepsy, only a small number of studies investigated the relationship between BDNF serum levels and epilepsy, and these studies obtained inconsistent results. The aim of this study was to elucidate BDNF serum levels in epilepsy cases. METHODS: Collectively, group of 143 patients (n = 143) were included in this study and subsequently divided into two groups consisting of individuals after singular generalized tonic-clonic seizures (n = 50) and patients with chronic epilepsy (n = 93). The samples from patients with acute epilepsy were collected 1-3 hours and 72 h after seizure, and a single collection was performed from patients with chronic epilepsy. These samples were compared to the control group (n = 48) using ELISA. RESULTS: In the present study, we observed a significant decrease of BDNF serum levels in patients after generalized tonic-clonic seizures compared to the control group. Furthermore, the observed decrease of BDNF levels in this group was sustained at 1 and 72 h after seizure insult. We did not show the relationship between BDNF levels and age, etiology of epilepsy and the duration of illness. SIGNIFICANCE: Our results and the findings of previous studies indicate that the serum BDNF level significantly decreases after seizures and should be considered when measuring BDNF in patients with chronic epilepsy. It might be also influenced by neurodegenerative processes, which may be involved in the etiopathogenesis of particular epilepsy syndromes.

Corrigendum to "Comparative Analysis of the Occurrence and Role of CX3CL1 (Fractalkine) and Its Receptor CX3CR1 in Hemophilic Arthropathy and Osteoarthritis".

[This corrects the article DOI: 10.1155/2020/2932696.].

Economic Costs of Cardiovascular Diseases in Poland Estimates for 2015-2017 Years.

BACKGROUND: Cardiovascular diseases are associated with growing public and private expenditure on healthcare regardless geographic region. Therefore, it is necessary to accurately estimate the overall societal costs-both direct and indirect expenses from the perspective of patients, caregivers and employers. RESEARCH DESIGN: The aim of this paper is to determine the direct and indirect costs related to cardiovascular diseases in Poland from 2015 to 2017. All costs are estimated based on data available in the public domain and obtained from the major Polish institutions. Indirect costs were calculated using a modified human capital approach. RESULTS: The financial burden of cardiovascular diseases in Poland is significant. This study revealed that total costs (direct and indirect) of cardiovascular diseases, for 2015-2017, range from 34.9 bn PLN (8.2 bn EUR) to over 40.9 bn PLN (9.6 bn EUR). Total direct cost and indirect costs were approximately 6.1 bn PLN (1.4 bn EUR) (16%) and 31.3 bn PLN (7.3 bn EUR) (84%), respectively. CONCLUSION: Collectively, the estimated direct and indirect cost of cardiovascular diseases provide a useful input for economic impact assessments of public health programs and health technology analyses.

Comparative Analysis of the Occurrence and Role of CX3CL1 (Fractalkine) and Its Receptor CX3CR1 in Hemophilic Arthropathy and Osteoarthritis.

OBJECTIVE: Hemophilic arthropathy is characterized by recurrent bleeding episodes in patients with hemophilia leading to irreversible joint degeneration. The involvement of CX3CL1 (fractalkine) and its receptor CX3CR1 was observed in the pathogenesis of numerous arthritis-associated diseases. Taking this into account, we have presented a study investigating the role of the CX3CL1/CX3XR1 axis in the course of hemophilic arthropathy, including the CX3CL1-dependent expression of CD56+, CD68+, and CD31+ cells along with evaluation of articular cartilage and synovial membrane morphology. METHODS: The study was carried out using cases (n = 20) of end-stage hemophilic arthropathy with a severe type of hemophilia A and control cases (n = 20) diagnosed with osteoarthritis. The biofluids including blood serum and synovial fluid were obtained intraoperatively for the evaluation of CX3CL1 using the ELISA test. Tissue specimens including articular cartilage and synovial membrane were similarly collected during surgery and stained immunohistologically using selected antibodies including anti-CX3CR1, anti-CD56, anti-CD68, and anti-CD31. Additionally, the analysis included the assessment of articular cartilage, synovial membrane, and blood vessel morphology. RESULTS: In our study, we have documented increased average concentration of CX3CL1 in the blood serum of the study group (7.16 ± 0.53 ng/ml) compared to the control group (5.85 ± 0.70 ng/ml) without statistically significant difference in synovial fluid concentration at the same time. We have observed an increased macrophage presence with more marked proliferation and fibrosis of the synovial membrane in the study group. Remaining results such as expression of CX3CR1 presence of NK cells and larger surface area of blood vessels within the synovial membrane were noted also without statistical significance. CONCLUSIONS: This study has demonstrated collective CX3CL1/CX3CR1 axis involvement in hemophilic arthropathy pathogenesis introducing new interesting diagnostics and a therapeutic target.

Overview and Analysis of the Cost of Drug Programs in Poland: Public Payer Expenditures and Coverage of Cancer and Non-Neoplastic Diseases Related Drug Therapies from 2015-2018 Years.

BACKGROUND: In Poland drug programmes developed by the Minister of Health and financed by the National Health Fund are special reimbursement frameworks of innovative, expensive, and mostly hospital based medical products used for a small number of patients. RESEARCH DESIGN: The research presented in this paper is based on data analysis published by the National Health Fund in Poland. The analysis focused on estimating public payer expenditure on drugs available within drug programmes from 2015 to 2018. RESULTS: In subsequent years, reimbursement of drugs used within drug programmes was associated with the National Health Fund budget expenditure of 635 mln USD, 755 mln USD, 854 mln USD, and 921 mln USD, respectively. Reimbursement of oncology drug programmes constituted 48.1%, 42.5%, 47.1%, and 52.4% and were approximately 305, 312, 402, 483 mln USD, whereas values of non-oncology drug programmes were approximately 330, 434, 452, and 438 mln USD which constituted 51.9%, 57.5%, 52.9%, and 47.6% respectively. CONCLUSION: Despite the fact that the expenditure on drug programs in Poland are increasing every year, they undoubtedly improve the patient's access to the most innovative oncological and nononcological therapies in the Polish healthcare system.

Significance of Omega-3 Fatty Acids in the Prophylaxis and Treatment after Spinal Cord Injury in Rodent Models.

Polyunsaturated fatty acids (ω-3 acids, PUFAs) are essential components of cell membranes in all mammals. A multifactorial beneficial influence of ω-3 fatty acids on the health of humans and other mammals has been observed for many years. Therefore, ω-3 fatty acids and their function in the prophylaxis and treatment of various pathologies have been subjected to numerous studies. Regarding the documented therapeutic influence of ω-3 fatty acids on the nervous and immune systems, the aim of this paper is to present the current state of knowledge and the critical assessment of the role of ω-3 fatty acids in the prophylaxis and treatment of spinal cord injury (SCI) in rodent models. The prophylactic properties (pre-SCI) include the stabilization of neuron cell membranes, the reduction of the expression of inflammatory cytokines (IL-1ß, TNF-α, IL-6, and KC/GRO/CINC), the improvement of local blood flow, reduced eicosanoid production, activation of protective intracellular transcription pathways (dependent on RXR, PPAR-α, Akt, and CREB), and increased concentration of lipids, glycogen, and oligosaccharides by neurons. On the other hand, the therapeutic properties (post-SCI) include the increased production of endogenous antioxidants such as carnosine and homocarnosine, the maintenance of elevated GSH concentrations at the site of injury, reduced concentrations of oxidative stress marker (MDA), autophagy improvement (via increasing the expression of LC3-II), and p38 MAPK expression reduction in the superficial dorsal horns (limiting the sensation of neuropathic pain). Paradoxically, despite the well-documented protective activity of ω-3 acids in rodents with SCI, the research does not offer an answer to the principal question of the optimal dose and treatment duration. Therefore, it is worth emphasizing the role of multicenter rodent studies with the implementation of standards which initially may even be based on arbitrary criteria. Additionally, basing on available research data, the authors of this paper make a careful attempt at referring some of the conclusions to the human population.

The role of progranulin (PGRN) in the modulation of anti-inflammatory response in asthma.

Asthma is one of the most common chronic diseases. Epidemiological studies show that asthma will develop among around 40% of children under six years old with symptoms of bronchial obstruction. Diagnosis of asthma is complicated, especially in the paediatric population. As a result, a lot of research is being carried out to establish the pathophysiology and to find new biomarkers of this disease. Progranulin (PGRN) is a recently discovered growth factor with many biological functions. PGRN has anti-inflammatory properties because it inhibits neutrophil degranulation and blocks tumor necrosis factor α (TNF-α) transmission. The underlying mechanisms are still being researched, but TNF-α is considered to be a cytokine responsible for neutrophilic inflammation in the airways and bronchial hyperresponsiveness. Therefore, PGRN, by lowering TNF-α concentration and stimulating regulatory T-cell (Treg) proliferation, relieves symptoms of bronchial inflammatory diseases. This article attempts to verify the current knowledge about basic pathophysiological mechanisms in asthma. We also summarise the most recent research advances in the role of PGRN in the respiratory system.

Concentration of microtubule associated protein tau (MAPT) in urine and saliva as a potential biomarker of traumatic brain injury in relationship with blood-brain barrier disruption in postmortem examination.

Traumatic brain injury (TBI) constitutes a frequent finding in medico-legal practice, including forensic autopsy and neuropathological examination. Despite clinico-scientific advances there is a need for identification of novel biomarkers considered for TBI diagnostics in ante- and postmortem cases. The role of MAPT protein as a biomarker in case of TBI was investigated in previous studies by examination of blood and cerebrospinal fluid obtained during forensic autopsies whereas less is known concerning its liberation and occurrence in other biofluids. The aim of this study was to elucidate and identify if elevated MAPT levels in other biofluids, such as urine, saliva, and vitreous body are also seen in TBI cases in population-based autopsy screening. The study was carried out using cases (n = 14) of severe head injury suspected as the cause of death and control cases (n = 13) of sudden death in the mechanism of cardiopulmonary failure. The biofluids, such as urine, saliva, and vitreous body were collected within ∼24 h after death and compared using ELISA test. Tissue specimens including brain and kidney were similarly collected during forensic autopsies. Brain specimens were stained immunohistologically with anti-Vimentin (V9) antibody and histologically using Mallory's trichrome method (to assess structural damage to blood-brain barrier elements) whereas kidney specimens were stained immunohistologically with anti-MAPT antibody (to assess the suitability of such a study in the diagnosis of TBI). In our study, we observed the elevated concentration levels of MAPT in saliva and urine. These changes were accompanied by damage to the structural elements of the blood-brain barrier (damage to the vascular endothelium and vascular basement membrane). According to this elevated cencentration levels of MAPT in this biofluids should be considered as TBI marker in postmortem examination even in cases where the head injury was not supposed to consist the direct cause of death.