Effect of single and repeated heat stress on chemical signals of heat shock response cascade in the rat’s heart

Exposure to sublethal heat stress activates a complex cascade of signaling events, such as activators (NO), signal molecules (PKCε), and mediators (HSP70 and COX-2), leading to implementation of heat preconditioning, an adaptive mechanism which makes the organism more tolerant to additional stress. We investigated the time frame in which these chemical signals are triggered after heat stress (41?±?0.5°С/45 min), single or repeated (24 or 72 h after the first one) in heart tissue of male Wistar rats. The animals were allowed to recover 24, 48 or 72 h at room temperature. Single heat stress caused a significant increase of the concentration of HSP70, NO, and PKC level and decrease of COX-2 level 24 h after the heat stress, which in the next course of recovery gradually normalized. The second heat stress, 24 h after the first one, caused a significant reduction of the HSP70 levels, concentration of NO and PKC?, and significant increase of COX-2 concentration. The second exposure, 72 h after the first heat stress, caused more expressive changes of HSP70 and NO in the 24 h-recovery groups. The level of PKC? was not significantly changed, but there was significantly increased COX-2 concentration during recovery. Serum activity of AST, ALT, and CK was reduced after single exposure and increased after repeated exposure to heat stress, in both time intervals. In conclusion, a longer period of recovery (72 h) between two consecutive sessions of heat stress is necessary to achieve more expressive changes in mediators (HSP70) and triggers (NO) of heat preconditioning.     

Increased nitric oxide formation followed by increased arginase activity induces relative lack of arginine at the wound site and alters whole nutritional status in rats almost within the early healing period

Nitric oxide (NO) production and free amino acid fluxes at the wound side during the first 3 days following cutaneous wound were investigated. Experiments were performed on Albino Oxford rats (n = 18) underwent cutaneous implantation of polyvinyl sponges. Intact animals (n = 6) were controls. Nitrites, nitrates, free amino acids and urea were measured both in plasma and wound fluids. Inducible nitric oxide synthase (iNOS) gene expressions at wound site were analyzed, too. The highest levels of both iNOS gene expression and its activity (increased wound fluid citrulline and nitrites) were at the first day. Wound fluid nitrates were significantly above plasma levels throughout the whole period, while molar nitrate to nitrite ratio steadily increased. It was associated with gradual increase of both ornithine and urea as well as steadily decreases of arginine and increases of phenylalanine at the wound site. Gradual decrease in glycine to branched-chain molar ratio was observed both in plasma and wound fluids. In conclusion, an early locally induced alterations in Arg metabolism, due to increased NO formation followed by increased arginase activity, produces relative lack of Arg at the wound site and disturbs nutritional status of the whole body almost within early healing period following cutaneous wound in rats. It is likely that NO autoxidation at the wound side is influenced by substrate availability.     

Influence of lipid metabolism disorders on venous thrombosis risk

Background: To investigate the influence of lipid metabolism disorders on the risk of deep vein thrombosis. Methods: A total of 200 subjects participated in the study, 100 of whom experienced DVT with or without PTE, and 100 healthy subjects representing the control group. We classified patients and controls in terms of serum concentrations of chylomicrons, LDL, IDL, VLDL, and HDL particles, as those with or without hyperlipoproteinemia and in terms of serum Lp (a) lipoprotein levels, as those with hyperLp (a) lipoproteinemia (serum Lp (a) values >0.3 g/L) and those without hyperLp (a) lipoproteinemia (serum Lp (a) values <0.3 g/L). Based on the modified and supplemented Fredrickson classification, participants with verified existences of hyperlipoproteinemia were classified into subgroups based on the type of hyperlipoproteinemia. Unconditional logistic regression was used to calculate ORs with 95% CIS as a measure of the relative risks for venous thrombosis in participants with hyperlipoproteinemia compared with those without hyperlipoproteinemia. The analysis was adjusted for all potential confounders (age, sex, obesity) related to the functionality of the lipid metabolism, and at the same time, may have an impact on the risk of venous thrombosis. Results: The results of the comparison of the mean values of individual lipid status parameters between the patient group and the control group clearly indicate higher concentrations of total cholesterol (5.93 mmol/L vs. 5.52 mmol/L), total triglycerides (1.58 mmol/L vs. 1.50 mmol/L), and LDL-cholesterol (3.83 mmol/L vs. 3.44 mmol/L) in the patient group relative to the control group, with a statistically significant difference observed only in the case of LDL-cholesterol concentrations. We have found that type IIa hyperlipoproteinemia is associated with a nearly double increased risk for deep vein thrombosis (OR 1.99; Cl 1.01-3.90), while type IIb, IV, or hyperLp (a) lipoproteinemia did not influence the risk (OR 1.22; 95% Cl 0.79-1.84; OR 0.89; 95% Cl 0.52-1.54 OR 1.85; 95% CI 0.84-4.04). Conclusions: Hypercholesterolemia doubles the risk of deep vein thrombosis development.     

The behaviour of the shoot apical meristem inChenopodium rubrum under conditions non-inductive for flowering

The results of different photoperiodic treatments preventing flowering and representing the control vegetative treatments in the studies of floral induction and differentiation were studied inChenopodium rubrum seedlings. A fully vegetative growth pattern of the meristem was maintained only in continuous light or after a photoperiodic treatment which consisted in a 15 min light break of the 8 h dark periods which themselves are a threshold for flowering inChenopodium. Light breaks applied to 10 h and longer dark periods did not prevent the changes resembling the early events of transition to flowering. Disappearance of zonal pattern, stimulation of apical growth, precocious initiation of leaf primordia and weakening of apical dominance have been observed. Flower formation did not follow. This work was supported by a grant from the Scientific Research Fund of SR Serbia.     

Relationship between osteology and aquatic locomotion in birds: determining modes of locomotion in extinct Ornithurae

The evolutionary history of aquatic invasion in birds would be incomplete without incorporation of extinct species. We show that aquatic affinities in fossil birds can be inferred by multivariate analysis of skeletal features and locomotion of 245 species of extant birds. Regularized discriminant analyses revealed that measurements of appendicular skeletons successfully separated diving birds from surface swimmers and flyers, while also discriminating among different underwater modes of swimming. The high accuracy of this method allows detection of skeletal characteristics that are indicative of aquatic locomotion and inference of such locomotion in bird species with insufficient behavioural information. Statistical predictions based on the analyses confirm qualitative assessments for both foot‐propelled (Hesperornithiformes) and wing‐propelled (Copepteryx) underwater locomotion in fossil birds. This is the first quantitative inference of underwater modes of swimming in fossil birds, enabling future studies of locomotion in extinct birds and evolutionary transitions among locomotor modes in avian lineage.     

Immunotherapy in the treatment of lymphoma

Relapsed or refractory non-Hodgkin's lymphomas, especially diffuse large B-cell lymphoma as well as relapsed or refractory Hodgkin lymphomas are hard-to-treat diseases. Patients who do not respond to initial therapy or experience relapse are treated with salvage regimens, and if eligible for aggressive therapy, treatment is continued with high-dose chemotherapy and autologous stem cell transplantation. Current therapy options can cure substantial numbers of patients, however for some it is still an uncurable disease. Numerous new drugs and cell therapies are being investigated for the treatment of relapsed or refractory lymphomas. Different types of immunotherapy options have shown promising results, and some have already become the standard of care. Here, we review immunotherapy options for the treatment of lymphoma and discuss the results, positions, practical aspects, and future directions of different drugs and cellular therapies for the treatment of this disease.