Patients with IgA nephropathy exhibit high systemic PDGF-DD levels

Background. Platelet-derived growth factor (PDGF) is a central mediator of mesangioproliferative glomerulonephritis (GN). In experimental mesangioproliferative GN, PDGF-DD serum levels, unlike PDGF-BB, increased up to 1000-fold. Methods. We assessed disease activity in 72 patients with GN, established a novel PDGF-D ELISA and then determined their PDGF-DD levels. In parallel, we studied renal PDGF-DD mRNA expression by RT-PCR. Results. PDGF-DD serum levels in patients with IgA nephropathy (IgAN) were significantly higher (1.67 ± 0.45 ng/ml) and in patients with lupus nephritis significantly lower (0.66 ± 0.86 ng/ml) compared to healthy controls (1.17 ± 0.46 ng/ml), while patients with focal segmental glomerulosclerosis, membranous GN and ANCA-positive vasculitis did not differ from controls. The subgroup of IgAN patients with elevated PDGF-DD levels (27% of samples) did not differ in their clinical features from those with normal PDGF-DD levels. In IgAN patients with repetitive PDGF-DD determinations, most exhibited only minor fluctuations of serum levels over time. Intrarenal PDGF-DD mRNA expression did not differ between controls and patients, suggesting an extrarenal source of the elevated PDGF-DD in IgAN. Conclusions. Serum PDGF-DD levels were specifically elevated in patients with IgAN, in particular in those with early disease, i.e. preserved renal function. Our data support the rationale for anti-PDGF-DD therapy in mesangioproliferative G

Data mining methods for the prediction of different forms of asthma

The article examines the diagnosis of bronchial asthma, cites the classification of the disease, proves the relevance of this research, and represents the result of primary data analysis by using a powerful tool for data analysis - Rapid Miner

Galanin diminishes cortical spreading depolarization across rodents – a candidate for treatment?

Galanin (Gal) is a neuropeptide with the potential to ameliorate cortical spreading depolarization (CSD), an electrophysiological phenomenon occurring after brain injury or in migraine aura. Gal is expressed in all cortical neurons both in rat and in mouse cortices. Here we investigated whether the effect of Gal on CSD previously described in the rat is conserved in the mouse cortex. In rats, the topical application of Gal to the cortex for 1 h did not induce any change in CSD amplitudes, propagation velocity, or threshold of elicitation. Rather, topical application of Gal for 3 h was necessary to obtain a significant decrease in these CSD parameters and to develop a remarkable increase in the KCl threshold to elicit a CSD in rat cortex. In contrast, the topical application of Gal on cortical surface for 1 h in mice was sufficient to significantly attenuate CSD amplitudes and increase threshold. A thinner cortex, a faster diffusion or different affinity/expression of receptors for Gal are possible reasons to explain this difference in the time course between rats and mice. Our data are relevant to postulate Gal as a potential target for inhibition of CSD under pathological situations such as stroke or ischemia. Significance statement The neuropeptide Galanin (Gal) is expressed in all neurons throughout the cerebral cortex, both in rats and mice, and is able to reduce or even inhibit Cortical Spreading Depolarization, thus, Gal has the potential to control neuronal excitability that may identify Gal as a target in drug development against CSD

Direct Effects of the Janus Kinase Inhibitor Baricitinib on Sensory Neurons

Therapeutically, the Janus kinase (Jak) 1/Jak2 inhibitor baricitinib reduces the pathology of rheumatoid arthritis and may also reduce pain. Here, we investigated whether baricitinib directly affects joint nociceptors. We recorded action potentials from nociceptive C- and A∂-fibers of the normal and inflamed knee joint in anesthetized rats to monitor their responses to innocuous and noxious joint rotation. In isolated and cultured dorsal root ganglion (DRG) neurons, we examined Stat3 activation using Western blots and monitored excitability using patch-clamp recordings. Intra-articular injection of baricitinib did not alter C- and A∂-fiber responses to innocuous and noxious rotations of the normal knee but reduced C-fiber responses to these stimuli in inflamed joints. Baricitinib prevented the increase in C-fiber responses to joint rotation evoked by interleukin (IL)-6 plus soluble interleukin-6 receptor (sIL-6R) but not the increase evoked by TNF. In DRG neurons, baricitinib blocked Stat3 activation by hyper-IL-6, and baricitinib or the Stat3 inhibitor Sta21 prevented induction of hyperexcitability by IL-6 plus sIL-6R. Thus, neuronal Jaks are involved in the generation of C-fiber hyperexcitability induced by inflammation and IL-6. Pain reduction by baricitinib may result, at least in part, from direct effects on joint nociceptors

Cortical spreading depolarization is a potential target for rat brain excitability modulation by Galanin

The inhibitory neuropeptide Galanin (Gal) has been shown to mediate anticonvulsion and neuroprotection. Here we investigated whether Gal affects cortical spreading depolarization (CSD). CSD is considered the pathophysiological neuronal mechanism of migraine aura, and a neuronal mechanism aggravating brain damage upon afflictions of the brain. Immunohistochemistry localized Gal and the Gal receptors 1-3 (GalR1-3) in native rat cortex and evaluated microglial morphology after exposure to Gal. In anesthetized rats, Gal was applied alone and together with the GalR antagonists M40, M871, or SNAP 37889 locally to the exposed cortex. The spontaneous electrocorticogram and CSDs evoked by remote KCl pressure microinjection were measured. In rat cortex, Gal was present in all neurons of all cortical layers, but not in astrocytes, microglia and vessels. GalR2 and GalR3 were expressed throughout all neurons, whereas GalR1 was preponderantly located at neurons in layers IV and V, but only in about half of the neurons. In susceptible rats, topical application of Gal on cortex decreased CSD amplitude, slowed CSD propagation velocity, and increased the threshold for KCl to ignite CSD. In some rats, washout of previously applied Gal induced periods of epileptiform patterns in the electrocorticogram. Blockade of GalR2 by M871 robustly prevented all Gal effects on CSD, whereas blockade of GalR1 or GalR3 was less effective. Although microglia did not express GalRs, topical application of Gal changed microglial morphology indicating microglial activation. This effect of Gal on microglia was prevented by blocking neuronal GalR2. In conclusion, Gal has the potential to ameliorate CSD thus reducing pathophysiological neuronal events caused by or associated with CSD

Конкуренция на рынке банковских услуг

Объектом исследования является конкуренция на рынке банковских услуг. Цель работы изучение теоретического, практического аспекта банковского продукта, выявить тенденции банковской конкуренцииThe object of the research is competition on the market of banking services. The aim of the work the study of the theoretical and practical aspect of banking product, to identify trends of banking competition