Alzheimer's disease (AD) is the most common type of dementia, but it is very difficult to diagnose with certainty, so many AD studies have attempted to find early and relevant diagnostic markers. Regulated upon activation, normal T cell expressed and secreted (RANTES, also known as C-C chemokine ligand) is a chemokine involved in the migration of T cells and other lymphoid cells. Changes in RANTES levels and its expression in blood or in cerebrospinal fluid have been reported in some neurodegenerative diseases, such as Parkinson's disease and multiple sclerosis, but also in metabolic diseases in which inflammation plays a role. The aim of this observational study was to assess RANTES levels in peripheral blood as clinical indicators of AD. Plasma levels of RANTES were investigated in 85 AD patients in a relatively early phase of AD (median 8.5 months after diagnosis; 39 men and 46 women; average age 75.7 years), and in 78 control subjects (24 men and 54 women; average age 66 years). We found much higher plasma levels of RANTES in AD patients compared to controls. A negative correlation of RANTES levels with age, disease duration, Fazekas scale score, and the medial temporal lobe atrophy (MTA) score (Scheltens's scale) was found in AD patients, i.e., the higher levels corresponded to earlier stages of the disease. Plasma RANTES levels were not correlated with cognitive scores. In AD patients, RANTES levels were positively correlated with the levels of pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-α, which is consistent with the well-known fact that AD is associated with inflammatory processes. RANTES levels were also positively correlated with insulin levels in AD patients, with insulin resistance (HOMA-R) and pancreatic beta cell function (HOMA-F). This study evaluated several clinical and metabolic factors that may affect plasma levels of RANTES, but these factors could not explain the increases in RANTES levels observed in AD patients. Plasma levels of RANTES appear to be an interesting peripheral marker for early stages of AD. The study was approved by the Ethics Committee of Institute of Endocrinology, Prague, Czech Republic on July 22, 2011.

• Klíčová slova
• Alzheimer’s disease, RANTES, biomarker, central nervous system, cognitive impairment, inflammation,
• Publikační typ
• časopisecké články MeSH

Indoleamine 2,3-dioxygenase 1 (IDO1), IDO2 and tryptophan 2,3-dioxygenase (TDO) represent some of the key immune regulators. Their increased activity has been demonstrated in a number of human malignancies but not yet in chronic myeloid leukemia (CML). In the present study, the activity of these enzymes was tested in 29 CML patients and 28 healthy subjects by monitoring the kynurenine (KYN)/tryptophan ratio. Serum samples taken prior to the therapy displayed a highly significant difference in KYN levels between the patient and control groups. However, increased KYN levels were detected in only 13 (44.8%) of these CML patients. The KYN levels in pretreatment sera of the patients correlated with the tumor burden. There was also a strong correlation between KYN levels and uric acid levels (UA). This suggests but does not prove the possible involvement of UA in activating IDO family of enzymes. Whenever tested, the increased KYN levels normalized in the course of the therapy. Patients with normal KYN levels in their pretreatment sera and subsequently treated with interferon-α, showed a transitory increase in their KYN levels. The present data indicate that CML should be added to the malignancies with an increased activity of the IDO family of enzymes and suggest that IDO inhibitors may be used in the treatment of CML patients.

• Klíčová slova
• 3-dioxygenase, CML, chronic myeloid leukemia, IDO, indoleamine 2, 3-dioxygenase, INFα, interferon- α, INFγ, interferon-γ, KTI, kynurenine/tryptophan index, KYN, kynurenine, NK, natural killer, PBMC, peripheral blood mononuclear cells, Ph+, Philadelphia chromosome positive, T regs, regulatory T cells, TDO, tryptophan 2, 3-dioxygenase, TKI, tyrosine-kinase inhibitors, TRY, tryptophan, UA, uric acid., chronic myeloid leukemia, indoleamine 2, kynurenine, tryptophan metabolism, uric acid,
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

It is now clear that a peripheral nerve lesion affects contralateral non-lesioned structures, and thus such a lesion can result in mirror image pain. The pathogenesis is still not exactly known, but there are some possible signaling pathways in the contralateral reaction of the nerve tissue after unilateral nerve injury. Potential signaling pathways of contralateral changes can be generally divided into humoral and neuronal mechanisms. Damage to peripheral nerves or spinal roots produces a number of breakdown products with development of an aseptic inflammatory reaction. Released immunomodulatory cytokines are believed to be transported via blood or cerebrospinal fluid into the contralateral part of the body affecting spinal roots, dorsal root ganglia or peripheral nerves. Because neurons are elements of a highly organized network, injury to the peripheral neuron results in signals that travel transneuronally into the central nervous system and affects the contralateral homonymous neurons. There is also evidence that spinal glia creates and maintain pathological pain. Additionally, there may be compensatory changes in behavior of animals with an impact on contralateral neurons, such as altered stance and motor performance or autonomic reflex changes. Although the transneuronal signaling pathway appears to be plausible, the humoral signaling pathway or other communication systems cannot be excluded at this time. Knowledge about these processes has clinical implications for the understanding of chronic neuropathic pain states, and, therefore, further studies will be necessary. Understanding signaling mechanisms in mirror image pain pathogenesis may provide novel therapeutic targets for the management of neuropathic pain.

• Klíčová slova
• contralateral reaction, cytokines, glia, nerve injury, neurons,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Inflammation is a key component of the immune system. It has important functions in both defense and pathophysiological events maintaining the dynamic homeostasis of a host organism including its tissues, organs and individual cells. On the cellular level it is controlled by more than 400 currently known genes. Their polymorphisms and environmental conditions give rise to different genotypes in human population. Pro-inflammatory genotype, which dominates in the present population, may be advantageous in childhood but not in elderly people because it is characterized by an increased vulnerability to, and intensity of, inflammatory reactions. These reactions may be the possible reasons of chronic inflammatory diseases, especially in old age. Better understanding of complex molecular and cellular inflammatory mechanisms is indispensable for detailed knowledge of pathogenesis of many diseases, their prevention and directed drug therapy. Here we summarize the basic current knowledge on these mechanisms.

• MeSH
• Alzheimerova nemoc etiologie   MeSH
• ateroskleróza etiologie   MeSH
• diabetes mellitus 2. typu etiologie   MeSH
• genotyp MeSH
• infekční nemoci imunologie   MeSH
• kardiovaskulární nemoci etiologie   MeSH
• lidé MeSH
• nádory etiologie   MeSH
• obezita imunologie   MeSH
• přirozená imunita MeSH
• signální transdukce MeSH
• stárnutí imunologie   MeSH
• zánět * komplikace   genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH