Acute kidney injury due to antimicrobial therapy.

One of the common causes of acute kidney injury (AKI) is drug nephrotoxicity. A large group of drugs associated with AKI includes a considerable number of antimicrobials. Clinical manifestations range from mild forms of tubular damage to significant deterioration of renal function requiring renal replacement therapy. Several mechanisms have been described, although the most common are acute interstitial nephritis, acute tubular necrosis, crystalic nephropathy or proximal/distal tubulopathy with electrolyte abnormalities. General risk factors for antimicrobial-induced AKI include pre-existing chronic kidney disease and concomitant use of drugs with nephrotoxic potential. Prevention and early recognition of AKI are the standard approach to mitigate AKI and avoid morbidity.

Bone metabolism parameters and their relation to cytogenetics in multiple myeloma.

OBJECTIVES: Our aim was to correlate serum levels of selected markers of bone metabolism and bone marrow microenvironment to cytogenetic changes in patients with multiple myeloma (MM). METHODS: We assed cytogenetic changes in 308 patients and correlated them with the following levels of bone marrow metabolism: thymidine kinase (TK), ß2-microglobulin (b-2-m), Dickkopf-1 protein (DKK-1), C-terminal telopeptide collagen-I (ICTP), N-terminal propeptide of type I procollagen (PINP), receptor for interleukin 6 (rIL-6), vascular cell adhesive molecule-1 (VCAM), soluble intercellular adhesion molecule-1, osteoprotegerin (OPG), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), syndecan-1 (SYN-1) and Fas antigen. RESULT: Individuals with delRB1 had lower levels of OPG (M = 7.39 vs. 5.46 pmol/L, p = .025) and VEGF (M = 304 vs. 196 pg/ml; p = .036). t(14;16) was associated with higher ß2m levels (M = 7.59 vs. 4.13 mg/L; p = .022) and lower DKK-1 levels (M = 4465 ng/L vs. 12,593). The presence of 1q21 gain was associated with higher levels of TK (M = 100.0 vs. 11.0 IU/L, p = .026) and lower levels of PINP (M = 49.3 vs. 67.4 mg/L, p = .030). CONCLUSIONS: Our analysis has shown, some cytogenetic changes, especially delRB1, t(14;16) and 1q21gain, which affect the components of the cytokine network in multiple myeloma.

A rare case of bifocal, extramedullary and hyposecretory relapse of multiple myeloma.

We present a rare extramedullary, bifocal, and hyposecretory manifestation of relapsed MM that could be mistaken for an infection. We stress the importance of complex evaluation including serum, urine, and bone marrow assessment and whole-body imaging.

Serum IL-6 in combination with synovial IL-6/CRP shows excellent diagnostic power to detect hip and knee prosthetic joint infection.

BACKGROUND: The diagnosis of prosthetic joint infection (PJI) is still a challenge in some patients after total joint replacement. Interleukin-6 (IL-6) strongly participates in the arrangement of the host-bacteria response. Therefore, increased levels of IL-6 should accompany every PJI. PURPOSE: The aim of the study was to show diagnostic characteristics of serum IL-6 for the diagnosis of prosthetic joint infection (PJI). We also compared the diagnostic values of serum IL-6 with synovial IL-6 (sIL-6) and synovial C-reactive protein (sCRP). STUDY DESIGN: We performed a prospective study of 240 patients in whom serum IL-6 was determined before total hip (n = 124) or knee (n = 116) reoperations. The PJI diagnosis was based on the MSIS (Musculoskeletal Infection Society) criteria (2011). Receiver operating characteristic plots were constructed for IL-6, sIL-6, and sCRP. RESULTS: PJI was diagnosed in 93 patients, and aseptic revision was diagnosed in 147 patients. The AUC (area under curve) for IL-6 was 0.938 (95% CI; 0.904-0.971). The optimal IL-6 cut-off value for PJI was 12.55 ng/L. Positive and negative likelihood ratios for IL-6 were 8.24 (95% CI; 4.79-14.17) and 0.15 (95% CI; 0.09-0.26), respectively. The optimal sIL-6 and sCRP cut-off values were 20,988 ng/L and 8.80 mg/L, respectively. Positive and negative likelihood ratios for sIL-6 were 40.000 (95% CI; 5.7-280.5) and 0.170 (95% CI; 0.07-0.417), respectively. Negative likelihood ratio for sCRP was 0.083 (95% CI; 0.022-0.314). CONCLUSIONS: The present study identified the cut-off values for serum/synovial IL-6 and synovial CRP for diagnostics of PJI at the site of THA and TKA and separately for each site. The diagnostic odds ratio for serum/synovial IL-6 and synovial CRP is very good. Simultaneous positivity of serum IL-6 either with synovial IL-6 or synovial CRP almost excludes false negative detection of PJI at the site of interest.

Electrocatalytic artificial carbonylation assay for observation of human serum albumin inter-individual properties.

Human serum albumin (HSA) is a multifunctional protein with ligand binding, transporting and buffering properties. Posttranslational modifications and ligand binding processes are closely related to albumin final functional status. In the last few decades, HSA has been characterized using a broad spectrum of methods, but quantitative data on the HSA's modifications among individuals have not been reported. The investigations presented here are based on the non-denaturing electrocatalytic screening of HSA samples isolated from the blood serum of healthy subjects. The electrocatalytic responses of the native protein (Rnat) varied depending on its modifications among individuals, which enable us to express the inter-individual variability. Consequently, the native HSA samples were subjected to ex vivo carbonylation with 50 mM methylglyoxal for 36 h. The differences between Rnat and the responses of artificially carbonylated protein (Rmod) corresponded with inter-individual binding capacity variations (ΔR = Rnat-Rmod). The coefficients of variation for the Rnat and ΔR values of purified HSA samples were estimated to be 8.5 and 23.2%, respectively. A sensitive non-denaturing electrocatalytic assay was utilized to provide new data about albumin inter-individual variations and evaluate its oxidative modifications and binding capacity, which could be used for further studies targeting not only on HSA but also other clinically important proteins.

Critical evaluation of colon submucosal microdialysis in awake, mobile rats.

Sensors able to record large bowel physiology and biochemistry in situ in awake rodents are lacking. Microdialysis is a mini-invasive technique that may be utilized to continuously deliver or recover low-molecular substances from various tissues. In this experiment we evaluated the feasibility of in vivo microdialysis to monitor extracellular fluid chemistry in the descending colon submucosa of conscious, freely moving rodents. Following surgical implantation of a microdialysis probe, male Wistar rats were housed in metabolic cages where they were analgized and clinically followed for four days with free access to standard diet and water. To assess local microcirculation and probe function, glucose, lactate, glucose-to-lactate ratio and urea clearance were determined in the dialysates from the three postoperative days with focus on the final 24-h period. In an attempt to mitigate the expected tissue inflammatory response, one group of animals had the catheters perfused with 5-aminosalicylic acid-enriched medium with final concentration 1 µmol/L. For verification of probe position and the assessment of the surrounding foreign body reaction, standard histological and immunohistochemical methods were employed. Microdialysis of rat gut is associated with considerable technical challenges that may lead to the loss of probe function and high drop-out rate. In this setting, limited data did not allow to draw any firm conclusion regarding local anti-inflammatory effectiveness of 5-aminosalicylic acid perfusion. Although intestinal microdialysis may be suitable for larger anesthetized animals, low reproducibility of the presented method compromises its routine experimental use in awake and freely moving small-sized rodents.

Long-term effects of three commercial cranberry products on the antioxidative status in rats: a pilot study.

Cranberry (Vaccinium macrocarpon Ait. Ericaceae) fruits and juice are widely used for their antiadherence and antioxidative properties. Little is known however about their effects on clinical chemistry markers after long-term consumption. This study was conducted to evaluate the effect of three commercial cranberry products, NUTRICRAN90S, HI-PAC 4.0, and PACRAN on the antioxidative status of rodents, divided into three experimental groups. The products were given as dietary admixtures (1500 mg of product/kg of stock feed) for 14 weeks to male Wistar rats (Groups 2-4) and a control Group 1 which received only stock feed. There were no significant cranberry treatment-related effects on oxidative stress parameters, catalase, glutathione peroxidase, glutathione reductase, glutathione transferase, superoxide dismutase, total antioxidant capacity, thiobarbituric acid reactive substances, advanced oxidation protein products, total SH-groups, or any other measured clinical chemistry markers. Hematological parameters, body weight, and food consumption were also unaffected by intake of cranberries. Only liver glutathione reductase activity and glutathione levels were significantly lower in Group 4 than in Group 1. Plasma alkaline phosphatase alone was significantly decreased in Group 2. No gross pathology, effects on organ weights, or histopathology were observed. No genotoxicity was found, and total cytochrome P450 level in liver was unaffected in all groups. The levels of hippuric acid and several phenolic acids were significantly increased in plasma and urine in Groups 2-4. The concentration of anthocyanins was under the detection threshold. The dietary addition of cranberry powders for 14 weeks was well tolerated, but it did not improve the antioxidative status in rats.

Natural feed additive of Macleaya cordata: safety assessment in rats a 90-day feeding experiment.

Macleaya cordata (Willd.) (Papaveraceae) is used as an active component in the natural feed additive Sangrovit. Sangrovit contains mixture of the intact aerial parts and the fraction of quaternary benzo[c]phenanthridine alkaloids from M. cordata (FQBA). In a 90-day pilot toxicity trial, Sangrovit and the FQBA were tested for safety. Male Wistar rats were fed for 90 days with 100, 7000 or 14000mg of Sangrovit or 600mg of FQBA in 1kg of feed. Body and organ weights, clinical chemistry and hematology markers, oxidative stress parameters, morphological structure of tongue, liver, ileum, kidney and heart samples, and total cytochrome P450 in liver were monitored. The results showed no statistically significant alterations in any parameter between control and treated animals, except for the group treated with 14000ppm Sangrovit that resulted in elevation of reduced glutathione level and superoxide dismutase activity in liver.

Use of glycogen phosphorylase BB measurement with POCT in the diagnosis of acute coronary syndromes. A comparison with the ELISA method.

BACKGROUND: Glycogen Phosphorylase BB (GPBB) is considered an early and specific marker of myocardial necrosis and ischemia. A POCT kit GPBB for diagnostic use has recently been approved. AIM: an evaluation of the correspondence of qualitative POCT GBPP measurements with ELISA test results. MATERIAL AND METHODOLOGY: 20 individuals with non-ST elevation myocardial infarction (non-STEMI) and 20 probands without acute coronary syndrome (ACS) were tested. GPBB (POCT, ELISA) in venous plasma (lithium-heparin) was assayed in all probands. RESULTS: individuals with non-STEMI had significantly higher GPBB ELISA values (32.3 vs. 6.1 microg/l; p < 0.01). GPBB sensitivity and specificity for non-STEMI presence 6 hours after chest pain generation were 100 %. No proband was classified in a different subgroup with POCT of GPBB (positive/negative). GPBB POCT correlate with a non- STEMI diagnosis (chi(2) 36.1; p <0.01). CONCLUSION: GPBB POCT measurement is comparable with ELISA test results. GPBB analysis could expand the diagnostic palette in the first hours after the onset of acute coronary syndrome.

Guanylins--agents with natriuretic effect.

Guanylins and uroguanylins are natriuretic peptides with different effects in many of tissues. In context with guanylins, the intestine-renal axis is presented. The overproduction of guanylin or uroguanylin leads to secondary diarrhea with stimulation of Cl(-) secretion. A diet high in salt lead especially to increased guanylin and uroguanylin secretion. Interesting applications with guanylins measurement could to be in hypertension diagnosis, monitoring of heart dysfunction treatment, intensive care etc.

Adiponectin added into the plasma of healthy probands does not affect platelet aggregability.

Six healthy non-obese probands without medical therapy and history of disease were tested. In all of them platelet aggregability with addition of human recombinant adiponectin in different concentrations (100; 75; 50 and 25 ng/l) were measured. It is concluded that increased level of adiponectin has no significant antiaggregation effect on platelets from individuals without hypoadiponectinemia.

Resistin - concentrations in persons with type 2 diabetes mellitus and in individuals with acute inflammatory disease.

UNLABELLED: Resistin is a recently discovered signal molecule, which could help elucidation of the pathophysiology of the insulin resistance and its correlation with obesity. As little information was available about resistin determination in venous blood at the time of our study, we focused on the question whether any correlation exists between persons with type 2 diabetes mellitus, with systemic inflammation, healthy persons and resistin concentrations and laboratory markers of inflammation, peptone, BMI. Differences of resistin values in these types of volunteers were studied as well. METHODS: Persons under study were divided into 3 groups: group A - with clinical signs of inflammatory disease of respiratory tract, leukocytosis > 10000/ul and CRP concentration > 50 mg/l (n = 35); group B - with well controlled type 2 DM treated by oral antidiabetic drugs, without clinical signs of inflammation and negative case history of acute disease (n = 12); group C - without clinical signs of inflammation and negative case history of acute disease (n = 77). For all volunteers we determined BMI index and examined resistin, leptin, interleukin 6, TNF-alpha, Na, K, Cl, insulin, cholesterol, HDL-cholesterol, LDL-cholesterol, triacylglycerols, creatinine, uric acid, ALT, AST, GMT, P, Mg and albumin in serum. RESULTS: Persons with clinical signs of severe inflammation had higher concentrations of Il6, CRP, resistin and a markedly lower BMI, decreased values of glucose, sodium, triacylglycerols, cholesterol, LDL-cholesterol and HDL-cholesterol compared to diabetics of type 2 (p < 0.05). Persons with clinical signs of severe inflammation showed significantly higher concentrations of TNF-alpha, Il6, CRP, resistin, glucose, leptin and considerably lower values of albumin, sodium and HDL-cholesterol than healthy individuals (p < 0.05). Persons with type 2 DM had markedly higher values of BMI, CRP, glucose, triacylglycerols, LDL-cholesterol, GMT and leptin, compared to healthy volunteers (p < 0.05). None of the three groups differed markedly in age or sex. Healthy volunteers show a significant correlation between leptin and resistin (correlation coefficient 0.82); this correlation was not found in patients with inflammation and type 2 DM. The group of volunteers with inflammations was found to have a significant positive correlation between resistin and inflammatory markers (correlation coefficient 0.3-0.5), negative correlation between resistin and cholesterol. We also found positive correlations between leptin and BMI as well as negative correlations between leptin and CRP. No significant correlations between resistin and other studied parameters were found in persons with type 2 DM. CONCLUSION: In healthy population a correlation was found between leptin and resistin concentrations in serum. In patients with severe inflammatory disease a correlation between resistin concentration and laboratory markers of inflammation was shown, however, no correlation was found between leptin and resistin. Resistin concentration in the serum of these patients is significantly higher ( p < 0.01) compared to healthy subjects and well controlled persons with type 2 DM with signs of insulin resistance. This may be due to a direct effect of inflammatory cytokines on resistin production. In persons with type 2 DM no significant correlations were found between resistin and other individual parameters ( insulin sensitivity markers, BMI or leptin). Resistin concentrations in persons with type 2 DM do not differ from concentrations of common population.

Adiponectin concentrations as a criterion of metabolic control in persons with type 2 diabetes mellitus?

UNLABELLED: Adiponectin (ADP) is an adipocytokin with many antiatherogenic properties; its decreased level is associated with numerous atherogenic diseases and syndromes (e.g. diabetes mellitus (DM), dyslipidemia, endothelial dysfunction, hypertension, and obesity). Decreased ADP values in blood may be an independent risk factor of atherosclerotic (ATS) complications. AIM OF THE STUDY: 1) Do persons with type 2 diabetes have lower ADP values than individuals without DM but with a high risk of ATS complications? 2) Do ADP values differ between persons with well controlled and persons with uncontrolled type 2 diabetes? We examined 109 patients of the Metabolic Center of Hospital Sternberk. Out of them, 58 had type 2 diabetes, others were individuals with variously expressed risk factors of early atherosclerosis (obesity, hypertension, age, family history, smoking, dyslipidemia, etc.). In all persons under this study the following parameters were determined in peripheral venous blood: adiponectin, resistin, leptin, ObRe, cholesterol, HDL-cholesterol, triacylglycerols, glucose, HbA1c, creatinine, urea, ALT, AST, CRP, homocysteine, thrombocyte aggregation after CPG induction. The whole group was divided according to the presence of type 2DM into two subgroups; persons with diabetes were divided into the well controlled and uncontrolled subgroups. All data obtained were processed statistically using the software SPSS for Windows and Medcalc. The adiponectin/BMI index correlated negatively with HbA1c value (correlation coefficient -0.37, p = 0.00053), triacylglycerols (-0.4, p = 0.000001), P-glucose (-0.3, p = 0.0017), uricemia (-0.35, p = 0.0007) and positively with HDL-cholesterol value (0.6, p=0.00001). Women had higher adiponectin values than men. Persons with hypertension and with diabetes mellitus, individuals with atherogenic lipotype or persons with inflammation signs had lower values than individuals without these diseases and syndromes. Persons with wellcontrolled diabetes mellitus had higher values than persons with uncontrolled diabetes (medians of the adiponectin/BMI index 9.7 vs. 6.7, p < 0.01). Persons with type 2 diabetes mellitus have lower ADP values than persons with a high ATS risk without diabetes mellitus. Persons with wellcontrolled diabetes mellitus (DM) and with satisfactory compensation have significantly higher ADP levels (independently of other metabolic parameters of DM control). ADP may be a new marker of metabolic control in persons with a high risk of atherosclerotic complications.

Preliminary experience with resistin assessment in common population.

Resistin is a signal peptide produced by adipose tissue. Mice models have confirmed that resistin may play an important role in insulin resistance. Its function in the human organism has not been elucidated yet. Since in common population the resistin concentrations are not known (no validated commercial set is available), we performed resistin assessment using the ELISA method (with satisfying analytical characteristics) in a population of 123 non-obese probands without signs of insulin resistance and/or inflammation. Mean resistin values amounted to 14.3 ng/ml (reference limit of 7.3-21.3 ng/ml).