Serum chitotriosidase: a circulating biomarker in polycythemia vera

ABSTRACT

Objectives: Serum chitotriosidase activity (CHIT1) is a biomarker of macrophage activation with an important role in inflammation-induced tissue remodeling and fibrosis. Macrophages have been described to play a crucial role in regulating pathological erythropoiesis in polycythemia vera (PV). The aim of this study was to evaluate CHIT1 in patients diagnosed with Philadelphia-negative myeloproliferative neoplasms (MPNs).

Methods: Using fluorometric assay, we measured CHIT1 in 28 PV, 27 essential thrombocythemia (ET), 17 primary myelofibrosis (PMF), 19 patients with secondary myelofibrosis and in 25 healthy controls.

Results: CHIT1 was significantly higher in PV (p?<?.001) and post-PV myelofibrosis (MF) transformation (post-PV MF) (p?=?.020), but not in ET (p?=?.080), post-ET MF transformation (p?=?.086), and PMF patients (p?=?.287), when compared to healthy controls. CHIT1 in PV was positively correlated with hemoglobin (p?=?.026), hematocrit (p?=?.012), absolute basophil count (p?=?.030) and the presence of reticulin fibrosis in the bone marrow (p?=?.023).

Discussion: A positive correlation between CHIT1 and these distinct laboratory PV features might imply macrophages closely related to clonal erythropoiesis as cells of CHIT1 origin. In addition, a positive association between CHIT1 and reticulin fibrosis might indicate its potential role in PV progression.

Conclusion: CHIT1 might be considered as a circulating biomarker in PV. Additional studies are needed to clarify the role of CHIT1 in promoting disease progression and bone marrow fibrosis in PV.     

CaV3.2 is the major molecular substrate for redox regulation of T-type Ca2+ channels in the rat and mouse thalamus

Although T-type Ca²⁺ channels in the thalamus play a crucial role in determining neuronal excitability and are involved in sensory processing and pathophysiology of epilepsy, little is known about the molecular mechanisms involved in their regulation. Here, we report that reducing agents, including endogenous sulfur-containing amino acid l -cysteine, selectively enhance native T-type currents in reticular thalamic (nRT) neurons and recombinant Ca_V3.2 (α1H) currents, but not native and recombinant Ca_V3.1 (α1G)- and Ca_V3.3 (α1I)-based currents. Consistent with this data, T-type currents of nRT neurons from transgenic mice lacking Ca_V3.2 channel expression were not modulated by reducing agents. In contrast, oxidizing agents inhibited all native and recombinant T-type currents non-selectively. Thus, our findings directly demonstrate that Ca_V3.2 channels are the main molecular substrate for redox regulation of neuronal T-type channels. In addition, because thalamic T-type channels generate low-threshold Ca²⁺ spikes that directly correlate with burst firing in these neurons, differential redox regulation of these channels may have an important function in controlling cellular excitability in physiological and pathological conditions and fine-tuning of the flow of sensory information into the central nervous system.     

Comparative pathomorphological,bacteriological and serological examination of broiler breeders and pheasants experimentally infected with Ornithobacterium rhinotracheale

The aim of the investigations was to determine the influence of Ornithobacterium rhinotracheale (ORT) on the development of pathomorphological lesions in the respiratory organs and on the health status of experimentally infected broiler breeders and pheasants from the rearing stage. There was no evidence of clinical signs in infected broiler breeder hens nor in the group of infected pheasants except for one bird in the latter group which exhibited slower movement and gasping. The frequency and intensity of pathomorphological lesions were higher in pheasants. The gross pathology findings were characterized mainly by redness of the mucosa of the upper respiratory tract and accumulation of mucous content in the nasal cavities, infraorbital sinuses, larynx and trachea. Histopathology confirmed the presence of inflammation of the upper respiratory tract. Lesions in the lungs included hyperaemia, granulomatous and fibrinous pneumonia. ORT was reisolated only from the group of infected pheasants. Reisolation was successful from the respiratory organs (trachea, larynx, infraorbital sinuses, and lungs) of eight out of 10 infected birds. The serological response in both species was characterized by rapid production of specific antibodies that reached a maximum level in the blood in the first week after experimental infection. The antibody titres decreased gradually and were maintained at a stable level until the 12th week after inoculation. Fourteen weeks post-inoculation specific antibodies could not be detected by enzyme-linked immunosorbent assay.     

Upregulation of the T-type calcium current in small rat sensory neurons after chronic constrictive injury of the sciatic nerve

Recent data indicate that peripheral T-type Ca2+ channels are instrumental in supporting acute pain transmission. However, the function of these channels in chronic pain processing is less clear. To address this issue, we studied the expression of T-type Ca2+ currents in small nociceptive dorsal root ganglion (DRG) cells from L4-5 spinal ganglia of adult rats with neuropathic pain due to chronic constrictive injury (CCI) of the sciatic nerve. In control rats, whole cell recordings revealed that T-type currents, measured in 10 mM Ba2+ as a charge carrier, were present in moderate density (20 +/- 2 pA/pF). In rats with CCI, T-type current density (30 +/- 3 pA/pF) was significantly increased, but voltage- and time-dependent activation and inactivation kinetics were not significantly different from those in controls. CCI-induced neuropathy did not significantly change the pharmacological sensitivity of T-type current in these cells to nickel. Collectively, our results indicate that CCI-induced neuropathy significantly increases T-type current expression in small DRG neurons. Our finding that T-type currents are upregulated in a CCI model of peripheral neuropathy and earlier pharmacological and molecular studies suggest that T-type channels may be potentially useful therapeutic targets for the treatment of neuropathic pain associated with partial mechanical injury to the sciatic nerve.     

A comprehensive study of parameters correlated with honey health benefits

One hundred honey samples of different floral origin (acacia, sunflower, meadow, and forest) collected from nine European countries (Serbia, Albania, Croatia, Montenegro, Romania, Bulgaria, Bosnia and Herzegovina, North Macedonia and Hungary) were analysed for various physicochemical, sensory, antioxidant and antibacterial parameters. The relative antioxidant capacity index and relative antibacterial index were calculated, integrated and expressed as a new property – Power of Honey, intended to be used to predict the health potential of a honey based on its antioxidant and antibacterial activities. Free acidity and colour coordinates L* and a* were chosen for building an artificial neural network model for the prediction of honey health potential. These were chosen based on the obtained correlations between the investigated parameters and in light of the simplicity of the analysis. This model successfully predicted the Power of Honey with a gained coefficient of determination of 0.856. Forest honey samples exhibited the highest Power of Honey. This novel approach should make it possible for honey producers to predict the honey health potential of a particular honey based on a quick and simple analysis.

One hundred honey samples of different floral origin (acacia, sunflower, meadow, and forest) collected from nine European countries were analysed for various physicochemical, sensory, antioxidant and antibacterial parameters.     

Incidence of diabetes mellitus among children of Italian migrants substantiates the role of genetic factors in the pathogenesis of type 1 diabetes

To investigate the role of genetic and environmental factors in the pathogenesis of type 1 diabetes mellitus (T1D), we carried out a study in Germany aimed at comparing the prevalence and incidence of T1D among children of migrant Italians from high-risk (Sardinia) and low-risk (continental Italy) regions versus German children. Children from Italy were identified by the “Baden-Wuerttemberg (BW) Diabetes Incidence Registry”, which registered 4017 newly diagnosed T1D patients, aged 0–14 years, between 1987 and 2003. Data relating to T1D children from Sardinia were elicited from more than 2000 questionnaires. Our findings were: (1) T1D is more frequent among German children than among children of Italian migrants [incidence rate (IR) 14.8/100,000/year, 95% confidence interval (CI) 14.4–15.4 vs. IR 10.8/100,000/year, 95% CI 8.2–13.6); (2) the incidence of T1D among Italian children residing in Germany is similar to that of Italian children in the home country (IR 10.8/100,000/year, 95% CI 8.2–13.6 vs. 8.4/100,000/year, 95% CI 7.9–8.9); (3) the prevalence of T1D among Sardinian children is higher than that among German children (0.11%, 95% CI 0.11–0.12) independent of the place where the Sardinian children are living (Sardinian children in Germany 2.3%, 95% CI 0.5–6.5 vs. Sardinian children in Sardinia 0.30%, 95% CI 0.27–0.32). Conclusion: Children from high- and low-risk areas of Italy have incidence rates of T1D that are closer to those of their native regions than to those of German children, indicating that genetic factors play a predominant role in the pathogenesis of T1D. Funding grants: none