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Abstract T-type calcium channels are important regulators of neuronal excitability. The mammalian brain expresses three T-type channel isoforms (Cav3.1, Cav3.2 and Cav3.3) with distinct biophysical properties that are critically regulated by temperature. Here, we test the effects of how temperature affects spike output in a reduced firing neuron model expressing specific Cav3 channel isoforms. The modeling data revealed only a minimal effect on baseline spontaneous firing near rest, but a dramatic increase in rebound burst discharge frequency for Cav3.1 compared to Cav3.2 or Cav3.3 due to differences in window current or activation/recovery time constants. The reduced response by Cav3.2 could optimize its activity where it is expressed in peripheral tissues more subject to temperature variations than Cav3.1 or Cav3.3 channels expressed prominently in the brain. These tests thus reveal that aspects of neuronal firing behavior are critically dependent on both temperature and T-type calcium channel subtype.

The anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase known for its oncogenic potential that is involved in the development of the peripheral and central nervous system. ALK receptor ligands ALKAL1 and ALKAL2 were recently found to promote neuronal differentiation and survival. Here, we show that inflammation or injury enhanced ALKAL2 expression in a subset of TRPV1+ sensory neurons. Notably, ALKAL2 was particularly enriched in both mouse and human peptidergic nociceptors, yet weakly expressed in nonpeptidergic, large-diameter myelinated neurons or in the brain. Using a coculture expression system, we found that nociceptors exposed to ALKAL2 exhibited heightened excitability and neurite outgrowth. Intraplantar CFA or intrathecal infusion of recombinant ALKAL2 led to ALK phosphorylation in the lumbar dorsal horn of the spinal cord. Finally, depletion of ALKAL2 in dorsal root ganglia or blocking ALK with clinically available compounds crizotinib or lorlatinib reversed thermal hyperalgesia and mechanical allodynia induced by inflammation or nerve injury, respectively. Overall, our work uncovers the ALKAL2/ALK signaling axis as a central regulator of nociceptor-induced sensitization. We propose that clinically approved ALK inhibitors used for non–small cell lung cancer and neuroblastomas could be repurposed to treat persistent pain conditions.

The introduction of some agricultural land which has partially or totally lost their production capacity is and will be a very important action of Romanian forestry. This extends the forest fund and improves the climatic conditions around the planting areas. The research was carried out in two improvement perimeters near Diviciorii Mari, which assumed measurements of tree diameters, heights and harvesting increment cores. After the analysis of the data and increment cores, the results were associated with climatic data and the stands were found to suffer from the effects of prolonged droughts. Also, these trees suffer from drying, windfalls and breaks of crowns due to the combination of droughts with slope and soil. The results obtained from the research were compared with the researches carried out at the Mineci-Ungureni Forest District between 1944 and 1955 and similarities were found regarding the influence of droughts on the radial and, implicitly, forest growths.

Introduction Sensitization of nociceptive neurons can lead to persistent pain in response to inflammation or injury. Identifying the mechanisms of peripheral sensitization has been key to defining the maladaptive long-lasting [...], The anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase known for its oncogenic potential that is involved in the development of the peripheral and central nervous system. ALK receptor ligands ALKAL1 and ALKAL2 were recently found to promote neuronal differentiation and survival. Here, we show that inflammation or injury enhanced ALKAL2 expression in a subset of TRPV1+ sensory neurons. Notably, ALKAL2 was particularly enriched in both mouse and human peptidergic nociceptors, yet weakly expressed in nonpeptidergic, large-diameter myelinated neurons or in the brain. Using a coculture expression system, we found that nociceptors exposed to ALKAL2 exhibited heightened excitability and neurite outgrowth. Intraplantar CFA or intrathecal infusion of recombinant ALKAL2 led to ALK phosphorylation in the lumbar dorsal horn of the spinal cord. Finally, depletion of ALKAL2 in dorsal root ganglia or blocking ALK with clinically available compounds crizotinib or lorlatinib reversed thermal hyperalgesia and mechanical allodynia induced by inflammation or nerve injury, respectively. Overall, our work uncovers the ALKAL2/ALK signaling axis as a central regulator of nociceptor-induced sensitization. We propose that clinically approved ALK inhibitors used for non-small cell lung cancer and neuroblastomas could be repurposed to treat persistent pain conditions.

Hepatitis C virus (HCV) represents a fundamental issue for public health, with long term evolution and the gradual appearance of several complications and associated pathologies. One of these pathologies is represented by cryoglobulinemic vasculitis, a disorder characterized by the appearance in the patient’s serum of the cryoglobulins, which typically precipitate at temperatures below normal body temperature (37°C) and dissolve again if the serum is heated. Here, we describe the case of a patient diagnosed with HCV that, during the evolution of the hepatic disease, developed a form of cryoglobulinemic vasculitis. The connection between the vasculitis and the hepatic disorder was revealed following treatment with interferon, with the temporary remission of both pathologies and subsequent relapse at the end of the 12 months of treatment, the patient becoming a non-responder. The particularity of the case is represented by both the severity of the vasculitic disease from its onset and the deterioration of renal function up to the predialitic phase, a situation not typical of the evolution of cryoglobulinemia. Taking into account the hepatic disorder, the inevitable evolution towards cirrhosis, and the risk of developing the hepatocellular carcinoma, close monitoring is necessary.

The purpose of this study is the identification of microflora present in the dog oral pathology, establishing connections between it and the clinical manifestations, and to make a correlation between clinical and microbiological aspects and the stages of periodontal disease. During this research 14 cases were diagnosed with periodontal disease: stage I on 3 patients (age of 3 years), stage II on 3 patients (age of 7, 6 years), stage III on 5 patients (age of 7 years) and stage IV on 2 patients (age of 10 years). In the initial stages (I, II) of periodontal disease we found gram positive bacillus arranged in a filament shape and in stages III and IV we encountered the growth of oral cocobacilli G-. The most effective antibiotics in our study is different depending of the stage of periodontal disease and was represented by Amoxiclav and Enroxil for stages I, III and IV, Amoxiclav and Ceftiofur for stage II. The oral microbiota is changing with evolution of periodontal disease, increasing the gram negative cocobacil population, especially Pseudomonas spp. Every individual presents a different sensitivity with an specific antibiogram.

Intercomparison exercises of radon instruments play an important part when it comes to domestic survey as well as international or national mapping in dwellings, soil or water. Therefore, it is of prime interest to improve and standardize technical methods of measurement and also to verify quality assurance through comparison between different instruments and techniques. In the present paper is described the latest intercomparison exercise performed between the Laboratory of Environmental Radioactivity (hereafter called LER) of our department and other 15 different teams around Europe. The test has been held at two radon reference sites located 60 km SW of Prague, Czech Republic.

The aim of this paper is obtaining and characterizing hydrogels based on different ratios of oxidized alginate (oA) and k-carrageenan (C), chemically cross-linked with adipic dihydrazide (adh). The alginate (A) was first oxidized with sodium metaperiodate in order to transform it into the dialdehyde derivative, a more reactive compound than alginate. A known procedure for oxidation of alginate with sodium metaperiodate in ethanol-water in order to improve alginate reactivity by transforming the hydroxyl end-groups into dialdehyde was used, preceded by a partially cleavage of the alginate chains. In the second stage, the mixture of dialdehydic derivative of oxidized alginate, k-carrageenan and glycerol subjected to reaction with adipic dihydrazide leads to a Semi-Interpenetrated Network covalently cross-linked alginate/k-carrageenan hydrogel (oACadh), based on the dihydrazone compound which is responsible for the chemical cross-linking. Pure alginate, k-carrageenan, oxidized alginate, adipic dihydrazide and the cross-linked hydrogel were characterized by: FTIR, XRD, and SEM.