Poznan University of Medical science is a prominent Polish medical university, located in the city of Poznań in western Poland. It traces its beginnings to the foundation of Poznań University in 1919, and was formed as a separate institution in 1950. It gained the status of uniwersytet in 2007. Wikipedia.
Rybakowski J.K.,Poznan University of Medical Sciences
World Journal of Biological Psychiatry | Year: 2011
Objectives. More than 60 years have passed since the introduction of lithium into modern psychiatry and special issues of Bipolar Disorders in 2009 and Neuropsychobiology in 2010 were devoted to this anniversary. Notwithstanding such a long tradition, a number of key articles on the neuropsychiatric aspects of lithium have appeared in recent years. Methods. This update was based on the most important original papers and reviews on lithium published in recent years. The main topics were the efficacy of lithium in mood disorders, with a special focus on cognitive functions, the neuroprotective effects of this ion and the potential of using lithium in neurology. Results. Clinical studies and reviews point to lithium being still a cornerstone for the prophylaxis of mood disorders, especially bipolar. The pro-cognitive and antisuicidal properties of lithium have been confirmed as an augmentation of antidepressants in treatment-resistant depression. The neuroprotective effects of lithium have been evidenced in both experimental research and in clinical studies using brain imaging. The possible use of lithium in the prophylaxis of dementia and in neurodegenerative disorders, such as Huntington's disease and amyotrophic lateral sclerosis is discussed. Conclusions. Although not promoted by pharmaceutical companies, lithium remains a highly important drug in neuropsychiatry. © 2011 Informa Healthcare.
Rybakowski J.K.,Poznan University of Medical Sciences
ACS Chemical Neuroscience | Year: 2014
The use of lithium is a cornerstone for preventing recurrences in bipolar disorder (BD). The response of patients with bipolar disorder to lithium has different levels of magnitude. About one-third of lithium-treated patients are excellent lithium responders (ELR), showing total prevention of the episodes. A number of clinical characteristics were delineated in patients with favorable response to lithium as regards to clinical course, family history of mood disorders, and psychiatric comorbidity. We have also demonstrated that temperamental features of hypomania (a hyperthymic temperament) and a lack of cognitive disorganization predict the best results of lithium prophylaxis. A degree of prevention against manic and depressive episodes has been regarded as an endophenotype for pharmacogenetic studies. The majority of data have been gathered from so-called "candidate" gene studies. The candidates were selected on the basis of neurobiology of bipolar disorder and mechanisms of lithium action including, among others, neurotransmission, intracellular signaling, neuroprotection or circadian rhythms. We demonstrated that response to lithium has been connected with the genotype of BDNF gene and serum BDNF levels and have shown that ELR have normal cognitive functions and serum BDNF levels, even after long-term duration of the illness. A number of genome-wide association studies (GWAS) of BD have been also performed in recent years, some of which also focused on lithium response. The Consortium on Lithium Genetics (ConLiGen) has established the large sample for performing the genome-wide association study (GWAS) of lithium response in BD, and the first results have already been published. © 2014 American Chemical Society.
Leppert W.,Poznan University of Medical Sciences
Cancer Management and Research | Year: 2010
Fentanyl is a strong opioid analgesic, which is commonly used in the form of a transdermal patch for the treatment of chronic cancer pain. An intranasal route of fentanyl administration is a novel treatment for breakthrough cancer pain (BTCP). The prevalence, assessment, and management of BTCP is outlined in this paper, and basic pharmacodynamic and pharmacokinetic properties, dosing guidelines, and clinical experience with the use of intranasal fentanyl in this indication are discussed. Intranasal fentanyl is an attractive and convenient mode of BTCP treatment in opioid-tolerant patients due to its quick onset and short duration of action, noninvasive administration route, high bioavailability, and avoidance of a hepatic first-pass effect. Until now, few clinical trials have been conducted with intranasal fentanyl, but all have confirmed its usefulness and acceptability in BTCP treatment. Intranasal fentanyl may be used in opioid-tolerant patients without nasal pathologies. The dose should be titrated in each patient regardless of the regular opioid dose administered. Future studies should compare intranasal fentanyl with other fentanyl formulations used for BTCP management, and with analgesia, adverse effects, and quality of life taken into consideration. © 2010 Leppert.
Ksiaz;ek K.,Poznan University of Medical Sciences
Ageing Research Reviews | Year: 2013
Human peritoneal mesothelial cells (HPMCs) dominate within the peritoneal cavity and thus play a central role in a variety of intraperitoneal processes, including the transport of water and solutes, inflammation, host response, angiogenesis, and extracellular matrix remodeling. In addition, they contribute to the development of abdominal adhesions, peritonitis, endometriosis, cancer cell metastases, and peritoneal dialysis complications. For less than a decade the primary cultures of omental HPMCs have also been used as an experimental tool in studies on cellular aging. This paper provides the first comprehensive overview of the current state of art on molecular mechanisms underlying HPMC senescence in vitro. Special attention is paid to the causes of the very fast dynamics of HPMC senescence, and in particular to the role of non-telomeric DNA damage, the autocrine activity of TGF-β1, and the causative effects of oxidative stress. In addition, some clinical manifestations of HPMC senescence will be discussed, including its interplay with organismal aging, peritoneal dialysis, and cancer progression. © 2013 Elsevier B.V.
Wysocki P.J.,Poznan University of Medical Sciences
Expert Opinion on Investigational Drugs | Year: 2010
Importance of the field: Hepatocellular cancer (HCC) is the fifth most common malignancy worldwide and third leading cause of cancer death. HCC is highly resistant to conventional systemic therapies, and prognosis for advanced HCC patients remains poor. However, identification of signaling pathways responsible for HCC growth and progression such as RAS/RAF/MEK/ERK or PI3K/AKT/ mTOR has determined crucial molecular targets and led to development of novel promising targeted therapies. Areas covered in this review: This article presents molecular mechanisms responsible for development and progression of HCC and strategies aimed to block important molecules involved in signal transduction. It also reviews the clinical studies evaluating efficacy and safety of novel targeted approaches for treatment of this malignancy. What the reader will gain: Inhibition of molecular targets (ligands, membrane receptors and receptor-associated kinases) represents a promising strategy for treatment of HCC; in the case of sorafenib, this has already been demonstrated to significantly improve survival of advanced HCC patients. This article reviews novel therapeutic approaches that are based on combinations of different targeted agents with or without classic cytotoxic drugs. Take home message: Despite significant progress, advanced HCC remains an incurable disease, and the overall efficacy of recently approved targeted therapy (sorafenib) remains moderate. It is to be hoped that several ongoing clinical trials evaluating novel targeted approaches for treatment of HCC will lead to further improvement in the management of advanced disease. © 2010 Informa UK Ltd.
Rybakowski J.K.,Poznan University of Medical Sciences
Journal of Affective Disorders | Year: 2012
Objectives: The reason why depression may respond poorly to treatment with antidepressant drugs may be connected with the features of bipolarity. Evidence to this effect has accumulated in recent studies of various kinds of depression in mood disorders. Additional evidence for such a connection may be the efficacy of mood-stabilizing drugs in the augmentation of antidepressants in treatment-resistant depression. Methods: This review is based on clinical and psychopharmacological research performed over the past five years. The clinical investigation was based on the response to antidepressants of bipolar depression or to symptoms of hypomania, assessed mainly by the Mood Disorder Questionnaire (MDQ) and the Hypomania Checklist-32 (HCL-32). The psychopharmacological research tested the efficacy of augmentation of antidepressants in treatment-resistant depression by mood-stabilizing drugs of the 1st and 2nd generations. Results: A number of studies have pointed to an association between bipolar depression, or symptoms of hypomania and an inadequate response to antidepressants. Such a connection was also found in the Polish TRES-DEP study which included 1051 depressed patients. Pharmacological studies have demonstrated the efficacy of first generation mood-stabilizing drugs (lithium, carbamazepine) and second generation drugs (quetiapine, olanzapine, risperidone, ziprasidone, lamotrigine) for augmentation of antidepressants in treatment-resistant depression. Some evidence has been presented that mixed depressive episodes may also belong to this category. Conclusions: The results of these clinical and psychopharmacological studies appear to confirm an association between bipolarity and a poor response of depression to treatment with antidepressant drugs. © 2011 Elsevier B.V.
Grygiel-Gorniak B.,Poznan University of Medical Sciences
Nutrition Journal | Year: 2014
Peroxisome proliferator-activated receptors are expressed in many tissues, including adipocytes, hepatocytes, muscles and endothelial cells; however, the affinity depends on the isoform of PPAR, and different distribution and expression profiles, which ultimately lead to different clinical outcomes. Because they play an important role in lipid and glucose homeostasis, they are called lipid and insulin sensors. Their actions are limited to specific tissue types and thus, reveal a characteristic influence on target cells. PPARα mainly influences fatty acid metabolism and its activation lowers lipid levels, while PPARγ is mostly involved in the regulation of the adipogenesis, energy balance, and lipid biosynthesis. PPARβ/δ participates in fatty acid oxidation, mostly in skeletal and cardiac muscles, but it also regulates blood glucose and cholesterol levels. Many natural and synthetic ligands influence the expression of these receptors. Synthetic ligands are widely used in the treatment of dyslipidemia (e.g. fibrates - PPARα activators) or in diabetes mellitus (e.g. thiazolidinediones - PPARγ agonists). New generation drugs - PPARα/γ dual agonists - reveal hypolipemic, hypotensive, antiatherogenic, anti-inflammatory and anticoagulant action while the overexpression of PPARβ/δ prevents the development of obesity and reduces lipid accumulation in cardiac cells, even during a high-fat diet. Precise data on the expression and function of natural PPAR agonists on glucose and lipid metabolism are still missing, mostly because the same ligand influences several receptors and a number of reports have provided conflicting results. To date, we know that PPARs have the capability to accommodate and bind a variety of natural and synthetic lipophilic acids, such as essential fatty acids, eicosanoids, phytanic acid and palmitoylethanolamide. A current understanding of the effects of PPARs, their molecular mechanisms and the role of these receptors in nutrition and therapeutic treatment are delineated in this paper. © 2014 Grygiel-Górniak; licensee BioMed Central Ltd.
Rybakowski J.K.,Poznan University of Medical Sciences
CNS Drugs | Year: 2013
Mood stabilizers form a cornerstone in the long-term treatment of bipolar disorder. The first representative of their family was lithium, still considered a prototype drug for the prevention of manic and depressive recurrences in bipolar disorder. Along with carbamazepine and valproates, lithium belongs to the first generation of mood stabilizers, which appeared in psychiatric treatment in the 1960s. Atypical antipsychotics with mood-stabilizing properties and lamotrigine, which were introduced in the mid-1990s, form the second generation of such drugs. The response of patients with bipolar disorder to mood stabilizers has different levels of magnitude. About one-third of lithium-treated patients are excellent responders, showing total prevention of the episodes, and these patients are clinically characterized by an episodic clinical course, complete remission, a bipolar family history, low psychiatric co-morbidity and a hyperthymic temperament. It has been suggested that responders to carbamazepine or lamotrigine may differ clinically from responders to lithium. The main phenotype of the response to mood stabilizers is a degree of prevention against recurrences of manic and depressive episodes during long-term treatment. The most specific scale in this respect is the so-called Alda scale, where retrospective assessment of lithium response is scored on a 0-10 scale. The vast majority of data on genetic influences on the response to mood stabilizers has been gathered in relation to lithium. The studies on the mechanisms of action of lithium and on the neurobiology of bipolar disorder have led to the identification of a number of candidate genes. The genes studied for their association with lithium response have been those connected with neurotransmitters (serotonin, dopamine and glutamate), second messengers (phosphatidyl inositol [PI], cyclic adenosine-monophosphate [cAMP] and protein kinase C [PKC] pathways), substances involved in neuroprotection (brain-derived neurotrophic factor [BDNF] and glycogen synthase kinase 3-β [GSK-3β]) and a number of other miscellaneous genes. There are no published pharmacogenomic studies of mood stabilizers other than lithium, except for one study of the X-box binding protein 1 (XBP1) gene in relation to the efficacy of valproate. In recent years, a number of genome-wide association studies (GWAS) in bipolar disorders have been performed and some of those have also focused on lithium response. They suggest roles for the glutamatergic receptor AMPA (GRIA2) gene and the amiloride-sensitive cation channel 1 neuronal (ACCN1) gene in long-term lithium response. A promise for better elucidating the genetics of lithium response has been created by the formation of the Consortium on Lithium Genetics (ConLiGen) to establish the largest sample, to date, for the GWAS of lithium response in bipolar disorder. The sample currently comprises more than 1,200 patients, characterized by their response to lithium treatment according to the Alda scale. Preliminary results from this international study suggest a possible involvement of the sodium bicarbonate transporter (SLC4A10) gene in lithium response. It is concluded that the pharmacogenetics of response to mood stabilizers has recently become a growing field of research, especially so far as the pharmacogenetics of the response to lithium is concerned. Clearly, the ConLiGen project is a highly significant step in this research. Although the results of pharmacogenetic studies are of significant scientific value, their possible practical implications are yet to be seen. © 2013 The Author(s).
Niedziela M.,Poznan University of Medical Sciences
Best Practice and Research: Clinical Endocrinology and Metabolism | Year: 2014
According to the literature, thyroid nodules (TNs) are quite rare in the first two decades of life and are predominantly non-cancerous, although cancerous TNs are more common in the first two decades of life than in adults. Therefore, it is important for clinicians to distinguish benign from malignant lesions preoperatively because the latter require a total thyroidectomy with or without neck lymph node dissection. A careful work-up and a fine-needle aspiration biopsy (FNAB) are mandatory to improve the preoperative diagnosis. High-resolution thyroid ultrasound and real-time elastosonography are adjuvant presurgical tools in selecting patients for surgery, particularly those with indeterminate or non-diagnostic cytology. Elevated thyroid-stimulating hormone (TSH) level in a patient with a thyroid nodule is a new laboratory predictor of thyroid cancer risk. The majority of thyroid carcinomas derive from the follicular cell, whereas medullary thyroid carcinoma (MTC) derives from calcitonin-producing cells. Patients with MTC are screened for germ-line RET mutations to detect carriers and identify family members for prophylactic or therapeutic thyroidectomy. © 2013 Elsevier Ltd. All rights reserved.
Korczowska I.,Poznan University of Medical Sciences
World Journal of Orthopaedics | Year: 2014
Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease sustained by genetic factors. Various aspects of the genetic contribution to the pathogenetics and outcome of RA are still unknown. Several genes have been indicated so far in the pathogenesis of RA. Apart from human leukocyte antigen, large genome wide association studies have identified many loci involved in RA pathogenesis. These genes include protein tyrosine phosphatase, nonreceptor type 22, Peptidyl Arginine Deiminase type IV, signal transducer and activator of transcription 4, cytotoxic T-lymphocyte-associated protein 4, tumor necrosis factor-receptor associated factor 1/complement component 5, tumor necrosis factor and others. It is important to determine whether a combination of RA risk alleles are able to identify patients who will develop certain clinical outcomes, such myocardium infarction, severe infection or lymphoma, as well as to identify patients who will respond to biological medication therapy. © 2014 Baishideng Publishing Group Inc.