High pre-transplant serum nitrate levels predict risk of acute steroid-refractory graft-versus-host disease in the absence of statin therapy

Steroid-refractory graft-versus-host disease is a life-threatening complication after allogeneic stem cell transplantation. Evidence is accumulating that steroid-refractory graft-versus-host disease is associated with endothelial distress. Endothelial cell homeostasis is regulated by nitric oxide, and serum nitrates are derived from nitric oxide synthase activity or dietary sources. In this retrospective study based on 417 patients allografted at our institution we investigated whether quantification of serum nitrates could predict steroid-refractory graft-versus-host disease. Elevated pre-transplant levels of serum nitrates (>26.5 μM) predicted steroid-refractory graft-versus-host disease (P=0.026) and non-relapse mortality (P=0.028), particularly in combination with high pre-transplant angiopoietin-2 levels (P=0.0007 and P=0.021, respectively). Multivariate analyses confirmed serum nitrates as independent predictors of steroid-refractory graft-versus-host disease and non-relapse mortality. Differences in serum nitrate levels did not correlate with serum levels of tumor necrosis factor or C-reactive protein or expression of inducible nitric oxide synthase in blood cells. Patients with high pre-transplant nitrate levels had significantly reduced rates of refractory graft-versus-host disease (P=0.031) when pravastatin was taken. In summary, patients at high risk of developing steroid-refractory graft-versus-host disease could be identified prior to transplantation by serum markers linked to endothelial cell function. Retrospectively, statin medication was associated with a reduced incidence of refractory graft-versus-host disease in this endothelial high-risk cohort.     

Clinical and epidemiological features of Guillain‐Barré syndrome in the Western Balkans

The aim of this study was to define features of Guillain‐Barré syndrome in a large cohort of patients from three Western Balkans countries. Data from adult Guillain‐Barré syndrome (GBS) cases from 2009 to 2013 were retrospectively obtained from all tertiary health care centers. During the 5‐year period, 327 new cases of GBS were identified with a male to female ratio of 1.7 : 1. The most common GBS variants were demyelinating (65%) and axonal (12%). At nadir 45% of patients were chair‐bound, confined to bed, or required assisted ventilation, while 5% died. The crude incidence of GBS in Serbia and Montenegro was 0.93 per 100,000 population, and age‐adjusted incidence according to the world standard population was 0.86 per 100,000. Incidence was particularly high in 50‐ to 80‐year‐old men. Statistically significant seasonal variations of GBS were not observed. This study of patients with GBS in the Western Balkans allows us to prepare the health system better and to improve the management of patients. This study also opens opportunities for international collaboration and for taking part in the multinational studies on GBS.     

Palladium(II) Complexes with N‐Heteroaromatic Bidentate Hydrazone Ligands: The Effect of the Chelate Ring Size and Lipophilicity on in vitro Cytotoxic Activity

Novel Pd(II) complex with N‐heteroaromatic Schiff base ligand, derived from 8‐quinolinecarboxaldehyde (q8a) and ethyl hydrazinoacetate (haOEt), was synthesized and characterized by analytical and spectroscopy methods. The structure of novel complex, as well as structures of its quinoline and pyridine analogues, was optimized by density functional theory calculations, and theoretical data show good agreement with experimental results. A cytotoxic action of the complexes was evaluated on cultures of human promyelocytic leukemia (HL‐60), human glioma (U251), rat glioma (C6), and mouse fibrosarcoma (L929) cell lines. Among investigated compounds, only complexes with quinoline‐based ligands reduce the cell numbers in a dose‐dependent manner in investigated cell lines. The observed cytotoxic effect of two isomeric quinoline‐based complexes is predominantly mediated through the induction of apoptotic cell death in HL‐60 cell line. The cytotoxicity of most efficient novel Pd(II) complex is comparable to the activity of cisplatin, in all cell lines investigated.     

Isometric torso muscle endurance profiles in adolescents aged 15–18: normative values for age and gender differences

Objective: The aim of this study was to establish normative values for torso muscle endurance in adolescents aged 15–18 years. It was hypothesized that torso endurance profiles of adolescents differs between males and females and between adolescents and adults.

Background: Decreased torso muscle endurance has been identified as a potential personal risk factor for low back pain development in both adolescents and later years together with being detrimental for athletic performance.

Design: Measurement of torso muscle endurance, established through four tests performed in random order in a healthy adolescent population.

Setting: High school in Novi Sad, Province of Vojvodina, Republic of Serbia.

Methods: Two hundred and ninety-four adolescents from one high school (178 males and 116 females) were grouped into four age strata. Selected isometric torso muscle endurance tests were: Biering-Sørensen test for extensor endurance; Flexor endurance test; right and left Side Bridge tests. The mean, ratio, standard deviation and 25th, 50th and 75th percentile scores were determined for each gender/age strata.

Results and conclusion: Males had higher lateral torso endurance than females. Adolescents in general demonstrate their peak lifetime endurance as they appear more endurable than children and comparable adult groups. These data of endurance times, their ratios and percentiles in healthy normal subjects form a database bridging existing data for children and adults that may be useful for guiding training and rehabilitation.     

Force–velocity relationship of leg extensors obtained from loaded and unloaded vertical jumps

Purpose

Resent research has suggested that loaded multi-joint movements could reveal a linear force–velocity (F–V) relationship. The aim of the present study was to evaluate the F–V relationship both across different types of vertical jumps and across different F and V variables.

Methods

Ten healthy subjects performed maximum various vertical jumps that were either loaded or unloaded by constant external forces of up to 30 % of their body weight. Both the maximum and averaged F and V data were recorded.

Results

The observed F–V relationships proved to be strong (median correlation coefficients ranged 0.78–0.93) and quasi-linear. Their F- and V-intercepts and the calculated maximum power (P) were highly reliable (0.85 < ICC < 0.98), while their concurrent validity with respect to their directly measured values was on average moderate-to-large. The obtained F–V relationships also revealed that (1) the assessment of maximum F and P could be somewhat more reliable and valid than the assessment of maximum V, (2) natural countermovement jumps should be employed rather than the jumps performed from a fixed squat position, while (3) both maximum and averaged F and V variables could be used despite revealing markedly different regression parameters.

Conclusions

The data generally reveal a reliable, valid, strong and quasi-linear F–V relationship across variety of vertical jumps and the recorded F and V variables. Therefore, we conclude that the loaded vertical jumps could be developed into a routine method for testing the force, velocity, and power generating capacity of leg extensors.     

Potential Dual Immunomodulatory Role of VEGF in Ulcerative Colitis and Colorectal Carcinoma

Objective. Progression from ulcerative colitis (UC) toward colorectal carcinoma (CRC) is multistep process that includes gene alterations of tumor suppressor genes, such as p53 and p16. The aim of this study was to investigate the expression patterns of p16, p53 and VEGF in affected tissue and serum levels of cytokines TNF-α, IFN-γ, IL-4, IL-6, IL-10 and IL-17 in patients with UC and CRC, respectively.Matherials and methods. Serum levels of cytokine in patients with UC (n=24) and CRC (n=75) and in a healthy group (n=37) were analyzed by ELISA. Endoscopic biopsies specimens of UC and CRC were studied by immunohistochemical staining for p16, p53 and VEGF.Results. Patients with UC with presence of extraintestinal manifestations, complications, and positive staining of p16, p53 and VEGF respectively had higher serum levels of pro-inflammatory cytokines. Higher percentage of CRC patients had positive staining of p16, p53 and VEGF. CRC patients with positive staining of VEGF had decreased systemic values of pro-inflammatory IFN-γ and increased values of immunosuppressive IL-10.Conclusions. Relatively low IL-10 in patients with severe UC is insufficient to compensate IL-6 secretion and subsequently enhanced type 1/17 immune response. In UC patients, p16 and p53 induce enhanced VEGF expression and subsequent production of pro-inflammatory TNF-α and IL-6. In CRC patients VEGF seems to have immunosuppressive role. It appears that tumor suppressor gene-VEGF axis have dual role on immune response in inflammation of UC and tumor growth and progression of CRC.     

Cortical evoked potentials and somatosensory perception in chronic spinal cord injury patients

The correlation between somatosensory evoked potentials (SEPs) and sensory perception was studied in 110 patients with traumatic chronic spinal cord lesions. Perception thresholds over the legs for light touch, vibratory sensibility, temperature and thermal pain were tested together with recordings of tibial and peroneal SEPs. Tibial nerve SEPs correlated better with sensory perception than peroneal nerve SEPs. Normal tibial nerve SEPs were not present with absent or trace vibratory sensibility and vice versa. However, we found many exceptions to the correlation between temperature and pain perception and SEPs. Light touch, vibratory sensibility, and SEPs were highly correlated between each other, while temperature and pain perception correlated poorly to these other modalities. This represents an evident segregation of touch perception, vibratory sensibility and SEPs, which are thought to share dorsal columns as a common ascending pathway, and temperature and pain perception known to be related to the spinothalamic system.     

Functional iron deficiency and diastolic function in heart failure with preserved ejection fraction

Background

Functional iron deficiency (FID) is an independent risk factor for poor outcome in advanced heart failure with reduced EF, but its role in heart failure with preserved EF (HFPEF) remains unclear. We aimed to investigate the impact of FID on cardiac performance determined by pressure–volume loop analysis in HFPEF.

Methods

26 HFPEF patients who showed an increase in LV stiffness by pressure–volume (PV) loop analysis obtained by conductance-catheterization, performed exercise testing, echocardiographic examination including tissue Doppler and determination of iron metabolism: serum iron, ferritin and transferrin saturation. HFPEF patients who provided ferritin < 100 μg/l or ferritin of 100–299 μg/l in combination with transferrin saturation < 20% were defined as having FID. In 14 patients the expression of transferrin receptor was determined from available endomyocardial biopsies.

Results

Fifteen out of 26 HFPEF patients showed FID without anemia. Compared to control subjects and HFPEF patients without FID, HFPEF patients with FID showed an up-regulation of the myocardial transferrin receptor expression (p < 0.05). No differences between HFPEF patients with and without iron deficiency were found in heart dimensions, systolic and diastolic function obtained by PV-loop and echocardiography analysis. According to the linear regression analysis, LV stiffness was correlated with peak oxygen uptake (r = − 0.636, p < 0.001) but not with the ferritin level or transferrin saturation. No relation was found between FID and exercise capacity. The association of LV stiffness with exercise performance was independent from the level of iron deficiency.

Conclusion

In non-anemic HFPEF patients, cardiac dysfunction and impaired exercise capacity occur independently of FID.