Introduction: Increasing bacteria resistance to antibiotics is a major problem of healthcare system. There is a need for solutions that broaden the spectrum of bactericidal agents improving the efficacy of commonly used antibiotics. One of the promising directions of search are silver nanoparticles (obtained by different methods and displaying diversified physical and chemical properties), and their combination with antibiotics. Purpose: In this study, we tested the role of reactive oxygen species in the mechanism of synergistic antibacterial activity of gentamicin and Tween-stabilized silver nanoparticles against gentamicin-resistant clinical strains of Staphylococcus epidermidis. Methods: Synergistic bactericidal activity of gentamicin and silver nanoparticles stabilized with non-ionic detergent (Tween 80) was tested by the checkerboard titration method on microtiter plates. Detection of reactive oxygen species was based on the chemiluminescence of luminol. Results: Hydrophilic non-ionic surface functionalization of silver nanoparticles enabled the existence of non-aggregated active nanoparticles in a complex bacterial culture medium. Tween-stabilized silver nanoparticles in combination with gentamicin exhibited bactericidal activity against multidrug-resistant biofilm forming clinical strains of Staphylococcus epidermidis. A synergistic effect significantly decreased the minimal inhibitory concentration of gentamicin (the antibiotic with numerous undesirable effects). Gentamicin significantly enhanced the generation of reactive oxygen species by silver nanoparticles. Conclusion: Generation of reactive oxygen species by Tween-coated metallic silver nanoparticles was significantly enhanced by gentamicin, confirming the hypothesis of oxidative-associated mechanism of the synergistic antibacterial effect of the gentamicin-silver nanoparticles complex.

Transgelin is a 22-kDa protein involved in cytoskeletal organization and expressed in smooth muscle tissue. According to animal studies, it is a potential mediator of kidney injury and fibrosis, and moreover, its role in tumorigenesis is emerging in a variety of cancers. The study included 126 ambulatory patients with multiple myeloma (MM). Serum transgelin-2 concentrations were measured by enzyme-linked immunoassay. We evaluated associations between baseline transgelin and kidney function (serum creatinine, estimated glomerular filtration rate—eGFR, urinary markers of tubular injury: cystatin-C, neutrophil gelatinase associated lipocalin—NGAL monomer, cell cycle arrest biomarkers IGFBP-7 and TIMP-2) and markers of MM burden. Baseline serum transgelin was also evaluated as a predictor of kidney function after a follow-up of 27 months from the start of the study. Significant correlations were detected between serum transgelin-2 and serum creatinine (R = 0.29; p = 0.001) and eGFR (R = −0.25; p = 0.007). Transgelin significantly correlated with serum free light chains lambda (R = 0.18; p = 0.047) and serum periostin (R = −0.22; p = 0.013), after exclusion of smoldering MM patients. Patients with decreasing eGFR had higher transgelin levels (median 106.6 versus 83.9 ng/mL), although the difference was marginally significant (p = 0.05). However, baseline transgelin positively correlated with serum creatinine after the follow-up period (R = 0.37; p < 0.001) and negatively correlated with eGFR after the follow-up period (R = −0.33; p < 0.001). Moreover, higher baseline serum transgelin (beta = −0.11 ± 0.05; p = 0.032) significantly predicted lower eGFR values after the follow-up period, irrespective of baseline eGFR and follow-up duration. Our study shows for the first time that elevated serum transgelin is negatively associated with glomerular filtration in MM and predicts a decline in renal function over long-term follow-up.

Anorexia nervosa (AN) causes the highest number of deaths among all psychiatric disorders. Reduction in food intake and hyperactivity/increased anxiety observed in AN are also the core features of the activity-based anorexia animal model (ABA). Our aim was to assess how the acute ABA protocol mimics common AN complications, including gonadal and cardiovascular dysfunctions, depending on gender, age, and initial body weight, to form a comprehensive description of ABA as a reliable research tool. Wheel running, body weight, and food intake of adolescent female and male rats were monitored. Electrocardiography, heart rate variability, systolic blood pressure, and magnetic resonance imaging (MRI) measurements were performed. Immediately after euthanasia, tissue fragments and blood were collected for further analysis. Uterine weight was 2 times lower in ABA female rats, and ovarian tissue exhibited a reduced number of antral follicles and decreased expression of estrogen and progesterone receptors. Cardiovascular measurements revealed autonomic decompensation with prolongation of QRS complex and QT interval. The ABA model is a reliable research tool for presenting the breakdown of adaptation mechanisms observed in severe AN. Cardiac and hormonal features of ABA with underlying altered neuroendocrine pathways create a valid phenotype of a human disease.

Background and Objectives: Urine insulin-like growth factor-binding protein 7 (IGFBP-7), tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), and neutrophil gelatinase-associated lipocalin (NGAL) monomer are novel tubular kidney injury biomarkers. In multiple myeloma (MM), immunoglobulin free light chains (FLCs) play an integral role in renal impairment. This study aimed to investigate the correlation between new biomarkers and acclaimed parameters of renal failure, MM stage, and prognosis. Materials and Methods: The examined parameters included: urinary and serum cystatin-C, IGFBP-7, and TIMP-2, and urinary NGAL monomer in 124 enrolled patients. Results: Urinary and serum IGFBP-7 and urinary NGAL were higher among patients with an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, and positively correlated with urine light chains. Serum and urine IGFBP-7 and urine NGAL were greater among patients with a higher disease stage. In the whole study group, urinary concentrations of the studied markers were positively correlated with each other. In multiple linear regression, urinary IGFBP-7 and NGAL were associated with lower eGFR, independently of other urinary markers. Conclusions: Urinary IGFBP-7 and NGAL monomer may be useful markers of tubular renal damage in patients with MM. Biomarker-based diagnostics may contribute to earlier treatment that may improve renal outcomes and life expectancy in MM.

Proteinuria is an important sign of kidney diseases. Different protein patterns in urine associated with glomerular, tubular and overload proteinuria may be differentiated using the immunochemical detection of indicator proteins or via urinary proteins electrophoresis. Our aim was to characterize sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS-PAGE) using commercially available 4–20% gradient gels as a method to detect and differentiate proteinuria. Our laboratory-based study used excess urine samples collected for routine diagnostic purposes from adult patients of a tertiary-care hospital, including patients with albumin/creatinine < 30 mg/g and patients with dipstick proteinuria. The limit of albumin detection was estimated to be 3 mg/L. In 93 samples with albumin/creatinine < 30 mg/g, an albumin fraction was detected in 87% of samples with a minimum albumin concentration of 2.11 mg/L. The separation of 300 urine samples of patients with proteinuria revealed distinct protein patterns differentiated using the molecular weights of the detected proteins: glomerular (albumin and higher molecular weights) and two types of tubular proteinuria (“upper” ≥20 kDa and “lower” with lower molecular weights). These patterns were associated with different values of the glomerular filtration rate (median 66, 71 and 31 mL/min/1.72 m2, respectively, p = 0.004) and different proportions of multiple myeloma and nephrological diagnoses. As confirmed using tandem mass spectrometry and western blot, the SDS-PAGE protein fractions contained indicator proteins including immunoglobulin G, transferrin (glomerular proteinuria), α1-microglobulin, retinol-binding protein, neutrophil gelatinase-associated lipocalin, cystatin C, and β2-microglobulin (tubular), immunoglobulin light chain, myoglobin, and lysozyme (overflow). SDS-PAGE separation of urine proteins on commercially available 4–20% gradient gels is a reliable technique to diagnose proteinuria and differentiate between its main clinically relevant types.

Background and Aims Urine tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) seem to be novel kidney injury related biomarkers, especially in tubular cells damage. Free light chains (FLCs) are associated with renal failure in multiple myeloma (MM) and appear to have a prognostic value and indicate stages in MM. The aim of the study was to investigate the correlation between new biomarkers and acclaimed parameters of renal failure and markers of MM stages and prognosis. Method The study included 124 patients with MM in the mean age of 66 +/- 10 years, with median time from MM diagnosis of 30 (lower; upper quartile 14; 63) months. There were 7(6%) patients with smoldering MM, 80(65%) with ISS stage 1, 22 (18%)with stage 2 and 15 (12%) with stage 3 MM. Mean eGFR was 71 +/- 25 ml/min/1.73 m2 and 30 (24%) patients had eGFR &lt;60 ml/min/1.73 m2. The examined parameters included creatinine, urine NGAL, urine and serum cystatin-C, urine and serum FLC kappa and lambda, serum monoclonal protein, IGFBP-7 and TIMP-2 in serum and urine, WBC count, IL-6, NT-proBNP, serum albumin and β2-microglobulin. IGFBP-7 and TIMP-2 in serum were measured in a subgroup of 73 patients, including 26 (36%) with eGFR &lt;60 ml/min/1.73 m2. The association between between these parameters were determined by multivariate stepwise regression analysis. The p-value &lt;0.05 was considered statistically significant. Results Except for urine cystatin C and urine TIMP-2, all the studied markers were higher among patients with eGFR &lt;60 ml/min/1.73m2: urine NGAL: 23.3 (9.2; 68.4) vs. 7.8 (3.9; 16.8) ng/ml; p&lt;0.001; urine IGFBP-7: ; serum IGFBP-7: 86.2 (29.3; 125.0) vs. 33.7 (13.2; 61.5) ng/ml; p=0.003; and serum TIMP-2: 628 (498; 663) vs. 431 (360; 614) ng/ml; p=0.011, respectively. Serum and urine IGFBP-7 and urine NGAL were also higher among patients with ISS grade 3 comparing to the rest of the group (p=0.008, p&lt;0.001 and p=0.033, respectively). Patients with smoldering myeloma did not differ from those with symptomatic disease. No differences in studied markers were observed between patients with newly diagnosed MM in comparison to those who had been treated with one or more schemes. Only urinary IGFBP-7 differed between patients who were on treatment at the time of samples’ collection (median ng/ml) in comparison to untreated (median ng/ml; p=0.009). No differences in TIMP-2 and IGFBP-7 levels in patients divided according to MM state were observed (remission vs stable vs progressive disease). In whole studied group, urinary markers of tubular injury were interrelated: cystatin C correlated positively with NGAL monomer (R=0.22; p=0.016), IGFBP-7 (R=0.26; p=0.004) and TIMP-2 (R=0.22; p=0.016), NGAL correlated positively with IGFBP-7 (R=0.39; p&lt;0.001) and TIMP-2 (R=0.25; p=0.005), and IGFBP-7 correlated positively with TIMP-2 (R=0.31; p&lt;0.001). In multiple linear regression, the negative correlation between urinary IGFBP-7 and eGFR was independent of other studied urinary markers of tubular injury. However, after adjustment for confounders (age, smoldering versus symptomatic MM, ISS, LDH, remission versus stable or progressive disease, and the concentrations of involved urine light chains), only urinary NGAL was independently associated with eGFR. Conclusion Urine TIMP-2 and IGFBP-7 may be useful in investigating tubular renal damage in patients with chronic kidney injury among patients with MM. This can lead to noninvasive biomarker-targeted diagnostic interventions and contribute to early beginning of treatment that may improve life expectancy quality of life in MM.

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