Human benign Leydig cell tumor - Biochemical evaluation.

Recently we reported expressional alterations in 219 genes and their transcripts in Leydig cell tumors but nowadays there is still a lack of full basic biochemical characteristics of these tumors. The discovery of potential biochemical markers for tumor management from early detection, treatments, and control of therapy results may markedly supplement genetic data. Leydig cell micronodules were obtained from patients with azoospermia who were qualified for testicular biopsy. The biochemistry of Leydig cell tumors was analyzed using histological staining and spectrophotometric measurements of total proteins, carbohydrates, lipids, and nucleic acids. In addition, the levels of calcium (Ca2 +), copper (Cu2 +), zinc (Zn2 +), and selenium (Se2 +) ions were measured. When compared to healthy testis we revealed, for the first time, that in the interstitial tissue with Leydig cell tumors, great amounts of proteins, carbohydrates, lipids, and acids were dislocated from the seminiferous tubules. Measurements of organic compounds showed a decrease (P < 0.05) only in the Cu2 + content in Leydig cell tumors which may be related to their altered biochemical structure. This specific result may be promising for designing further approaches to manage this tumor based on combining morphological and molecular data.

Is triggering receptor expressed on myeloid cell 1 (TREM-1) protein a new marker of serious infectious complications in colorectal surgery?: case-matched pilot study.

PURPOSE: The purpose of the study was to evaluate the usefulness of the triggering receptor expressed on myeloid cell 1 (TREM-1) protein as a marker for serious infectious complications during laparoscopic colorectal surgery. METHODS: Sixty-four patients with colon or rectal cancer, who underwent an elective laparoscopic colorectal cancer surgery from November 2018 to February 2020, were included in the analysis. Blood samples of the TREM-1 protein testing were collected four times from each patient: before and on three following postoperative days (PODs). Patients were divided into two groups according to the presence of infectious complications. Subsequently, patients with infectious complications (group 1) were matched 1:1 with patients without complications (group 2). The case-matched analysis was done by selecting patients from the control group by age, ASA scale, cancer stage, and type of surgery. RESULTS: There was no significant difference in demographic and operative characteristics between the two groups. The median length of hospital stay was longer in group 1 than in group 2 (11 days vs. 5 days, p < 0.001). Preoperative measurements of TREM-1 protein did not differ between the two groups. There were no significant differences in the measurements on the first and third postoperative days. However, the median TREM-1 measurement was higher in group 1 on the second postoperative day (542 pg/ml vs. 399 pg/ml; p = 0.040). The difference was more apparent when only severe postoperative complications were considered. When compared to the group without any complications, the median TREM-1 level was significantly higher in the group with severe infection complications in POD 1, POD 2, and POD 3 (p < 0.05). The receiver operating characteristic (ROC) curve demonstrated that TREM-1 readings in POD 2 had a sensitivity of 83% and a specificity of 84% for the presence of severe infection complications at a value of 579.3 pg/ml (AUC 0.8, 95%CI 0.65-0.96). CONCLUSION: TREM-1 measurements might become a helpful predictive marker in the early diagnosis of serious infectious complications in patients following laparoscopic colorectal surgery.

Expanded insights into the neural component of the activity-based anorexia animal model - morphological changes in the enteric nervous system and altered pain perception.

Anorexia nervosa (AN) is an eating disorder characterized by distinct etiopathogenetic concepts that are gradually being linked together to unravel the dominant pathophysiological pathways underlying the disease. Excessive food restrictions, often accompanied by over-exercise and undertaken to lose weight, lead to the development of numerous complications. The biological concept of neurohormonal dysfunction in AN seems incomplete without demonstrating or excluding the role of the enteric nervous system (ENS). Using an animal model of activity-based anorexia (ABA), we conducted the preliminary assessment of the ENS structure. Here we show, in preparations stained by immunohistochemistry with anti- ChAT, anti-NOS, anti-PGP 9.5, anti-c-fos, and anti-TH antibodies, a lower density of cholinergic and nitrergic nerve fibers as well as reduced neuronal activity in myenteric plexus. Such structural and functional damage to the ENS may be responsible for a number of gastrointestinal symptoms that worsen the course of the disease. In addition, we expanded the study to address the unresolved issue of mechanical and thermal pain sensitivity in AN. The Von Frey and hot plate tests revealed, that in ABA animals, the pain threshold for mechanical stimulus decreases while for thermal increases. In this way, we have significantly supplemented the background of AN with potentially observable nervous system changes which may influence the evolution of the therapeutic approach in the future.

Administration of Warfarin Inhibits the Development of Cerulein-Induced Edematous Acute Pancreatitis in Rats.

Acute pancreatitis (AP) is a severe disease with high morbidity and mortality in which inflammation and coagulation play crucial roles. The development of inflammation leads to vascular injury, endothelium and leukocytes stimulation, and an increased level of tissue factor, which results in the activation of the coagulation process. For this reason, anticoagulants may be considered as a therapeutic option in AP. Previous studies have shown that pretreatment with heparin, low-molecular-weight heparin (LMWH), or acenocoumarol inhibits the development of AP. The aim of the present study was to check if pretreatment with warfarin affects the development of edematous pancreatitis evoked by cerulein. Warfarin (90, 180, or 270 µg/kg/dose) or saline were administered intragastrically once a day for 7 days consecutively before the induction of AP. AP was evoked by the intraperitoneal administration of cerulein. The pre-administration of warfarin at doses of 90 or 180 µg/kg/dose reduced the histological signs of pancreatic damage in animals with the induction of AP. Additionally, other parameters of AP, such as an increase in the serum activity of lipase and amylase, the plasma concentration of D-dimer, and interleukin-1ß, were decreased. In addition, pretreatment with warfarin administered at doses of 90 or 180 µg/kg/dose reversed the limitation of pancreatic blood flow evoked by AP development. Warfarin administered at a dose of 270 µg/kg/dose did not exhibit a preventive effect in cerulein-induced AP. Conclusion: Pretreatment with low doses of warfarin inhibits the development of AP evoked by the intraperitoneal administration of cerulein.

Salivary matrix metalloproteinase-9 (MMP-9) as a biomarker of periodontitis in pregnant patients with diabetes.

BACKGROUND: Pregnancy and diabetes increase the risk of developing pathological conditions in the periodontium. Salivary biomarkers, such as matrix metalloproteinase-9 (MMP-9), as well as antioxidants can be used as diagnostic indicators in monitoring periodontitis. OBJECTIVES: The aim of the study was to assess the periodontal status of pregnant women with regard to the presence of diabetes. In addition, we aimed to assess antioxidant activity and the level of MMP-9 in saliva in order to establish the optimal noninvasive determinants of periodontitis. MATERIAL AND METHODS: The study included 104 pregnant women: 35 patients had gestational diabetes mellitus (GDM); 30 patients had type 1 diabetes (T1D); and 39 patients did not have diabetes (the control group). The physical examination included the assessment of the approximal plaque index (API), the gingival index (GI), bleeding on probing (BOP), the probing pocket depth (PPD), and clinical attachment loss (CAL). In the saliva study, MMP-9 concentration as well as the ferric reducing ability of plasma (FRAP), and the activity of superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GPX) were measured. RESULTS: The pregnant patients with GDM and T1D had higher GI, BOP, PPD, and CAL scores than the control women (p < 0.0001, p = 0.0040, p = 0.0100, p = 0.0030, and p < 0.0001, p < 0.0009, p < 0.0001, p < 0.0001, respectively). The T1D patients had higher API scores as compared to the control women (p = 0.0010). The patients with periodontitis had higher salivary MMP-9 levels than the patients without periodontitis (p = 0.0001). The salivary antioxidant levels and activity were comparable among the study groups. The determinants of periodontitis (p < 0.0001) were MMP-9 concentration (p = 0.0008) and oral hygiene (p = 0.0001). The concentration of MMP-9 was also a useful determiner of the presence of periodontitis (p < 0.0001). CONCLUSIONS: In the pregnant women with diabetes, we observed worse gingival conditions, deeper periodontal pockets and greater attachment loss in comparison with the women from the control group. The concentration of MMP-9 in saliva is a good predictor of periodontitis and might be a useful tool for diagnosing periodontitis.

Analysis of biochemical parameters in an experimental model of chronic pancreatitis in rats.

BACKGROUND: Despite advanced research and great progress in understanding the chronic pancreatitis (CP) pathogenesis, no current causal treatment for the condition is available. For preclinical studies, the existence of a well-characterized CP animal model is essential. The aim of the study was to assess the impact of chronic pancreatitis on the antioxidant enzymes activity in rat blood serum and on the level of glutathione (intracellular antioxidant) in rat pancreas. METHODS: The experiments were carried out on the Wistar Kyoto rats in two groups: control and study group (CP), in which chemical induction of pancreatitis with dibutyl dichloride was performed. Serum enzyme activities of amylase, lipase, catalase and superoxide dismutase were analyzed. The levels of the following biochemical parameters were also investigated: total protein, albumin, calcium, magnesium, and triglycerides. Levels of low-molecular-weight thiols: reduced (GSH) and oxidized (GSSG) glutathione, were determined in pancreatic homogenates. RESULTS: Histopathological imaging of rat pancreatic parenchyma with induced inflammation confirmed focal lymphocytic interstitial chronic pancreatitis with fibrosis features and mild parenchymal atrophy, as well as pancreatic islets degeneration. In the CP group, we observed a statistically significant decrease in serum amylase and lipase activities and in total protein/albumin levels. Also, the elevated catalase activity was registered. In CP rats' tissues, we observed a 15-fold reduction in GSH levels. The other examined parameters remained unchanged. Clinically relevant are hypoalbuminemia and a moderate decrease in lipase activity. The described changes are most probably indicative of the impaired exocrine pancreas function, however without organ failure features.

Acute Changes in Serum Creatinine and Kinetic Glomerular Filtration Rate Estimation in Early Phase of Acute Pancreatitis.

In patients with acutely changing kidney function, equations used to estimate glomerular filtration rate (eGFR) must be adjusted for dynamic changes in the concentrations of filtration markers (kinetic eGFR, KeGFR). The aim of our study was to evaluate serum creatinine-based KeGFR in patients in the early phase of acute pancreatitis (AP) as a marker of changing renal function and as a predictor of AP severity. We retrospectively calculated KeGFR on day 2 and 3 of the hospital stay in a group of 147 adult patients admitted within 24 h from the onset of AP symptoms and treated in two secondary-care hospitals. In 34 (23%) patients, changes in serum creatinine during days 1-3 of the hospital stay exceeded 26.5 µmol/L; KeGFR values almost completely differentiated those with increasing and decreasing serum creatinine (area under receiver operating characteristic curve, AUROC: 0.990 on day 3). In twelve (8%) patients, renal failure was diagnosed during the first three days of the hospital stay according to the modified Marshall scoring system, which was associated with significantly lower KeGFR values. KeGFR offered good diagnostic accuracy for renal failure (area under receiver operating characteristic-AUROC: 0.942 and 0.950 on days 2 and 3). Fourteen (10%) patients developed severe AP. KeGFR enabled prediction of severe AP with moderate diagnostic accuracy (AUROC: 0.788 and 0.769 on days 2 and 3), independently of age, sex, comorbidities and study center. Lower KeGFR values were significantly associated with mortality. Significant dynamic changes in renal function are common in the early phase of AP. KeGFR may be useful in the assessment of kidney function in AP and the prediction of AP severity.

Soluble Complement Component 1q Receptor 1 (sCD93) Is Associated with Graft Function in Kidney Transplant Recipients.

Cluster of differentiation 93 (CD93), also known as complement component 1q receptor 1 is a transmembrane glycoprotein expressed in endothelial and hematopoietic cells and associated with phagocytosis, cell adhesion, angiogenesis and inflammation. The extracellular part, soluble CD93 (sCD93), is released to body fluids in inflammation. Data on sCD93 in kidney diseases are limited. Our aim was to evaluate serum sCD93 in long-term kidney transplant recipients as a marker of inflammation and endothelial dysfunction that may be potentially useful in early recognition of graft dysfunction. Seventy-eight adult patients with functioning kidney graft and stable clinical state were examined at least one year after kidney transplantation. Serum sCD93 was measured by enzyme immunosorbent assay. Estimated glomerular filtration rate (eGFR) and albuminuria or proteinuria were assessed at baseline and over one-year follow-up. Increased sCD93 was associated with lower baseline eGFR independently of the confounders. Moreover, sCD93 was negatively associated with eGFR during one-year follow-up in simple analysis; however, this was not confirmed after adjustment for confounders. Baseline sCD93 was positively associated with baseline albuminuria and with increased proteinuria during the follow-up. Serum sCD93 was not correlated with other studied inflammatory markers (interleukin 6, C-reactive protein, procalcitonin and C3 and C4 complement components). To the best of our knowledge, this is the first report regarding the concentrations of sCD93 in kidney transplant recipients and one of the first reports showing the inverse association between sCD93 and renal function. Serum sCD93 should be further evaluated as a diagnostic and prognostic marker in renal transplantation.

α1-Acid Glycoprotein and Dietary Intake in End-Stage Renal Disease Patients.

Management of end-stage renal disease (ESRD) patients requires monitoring each of the components of malnutrition-inflammation-atherosclerosis (MIA) syndrome. Restrictive diet can negatively affect nutritional status and inflammation. An acute-phase protein-α1-acid glycoprotein (AGP), has been associated with energy metabolism in animal and human studies. The aim of our study was to look for a relationship between serum AGP concentrations, laboratory parameters, and nutrient intake in ESRD patients. The study included 59 patients treated with maintenance hemodialysis. A 24 h recall assessed dietary intake during four non-consecutive days-two days in the post-summer period, and two post-winter. Selected laboratory tests were performed: complete blood count, serum iron, total iron biding capacity (TIBC) and unsaturated iron biding capacity (UIBC), vitamin D, AGP, C-reactive protein (CRP), albumin, prealbumin, and phosphate-calcium metabolism markers (intact parathyroid hormone, calcium, phosphate). Recorded dietary intake was highly deficient. A majority of patients did not meet recommended daily requirements for energy, protein, fiber, iron, magnesium, folate, and vitamin D. AGP correlated positively with CRP (R = 0.66), platelets (R = 0.29), and negatively with iron (R = -0.27) and TIBC (R = -0.30). AGP correlated negatively with the dietary intake of plant protein (R = -0.40), potassium (R = -0.27), copper (R = -0.30), vitamin B6 (R = -0.27), and folates (R = -0.27), p < 0.05. However, in multiple regression adjusted for confounders, only CRP was significantly associated with AGP. Our results indicate that in hemodialyzed patients, serum AGP is weakly associated with dietary intake of several nutrients, including plant protein.

Anti-inflammatory adipokines: chemerin, vaspin, omentin concentrations and SARS-CoV-2 outcomes.

Coronavirus disease 2019 (COVID-19) is associated with systemic inflammation. A wide range of adipokines activities suggests they influence pathogenesis and infection course. The aim was to assess concentrations of chemerin, omentin, and vaspin among COVID-19 patients with an emphasis on adipokines relationship with COVID-19 severity, concomitant metabolic abnormalities and liver dysfunction. Serum chemerin, omentin and vaspin concentrations were measured in serum collected from 70 COVID-19 patients at the moment of admission to hospital, before any treatment was applied and 20 healthy controls. Serum chemerin and omentin concentrations were significantly decreased in COVID-19 patients compared to healthy volunteers (271.0 vs. 373.0 ng/ml; p < 0.001 and 482.1 vs. 814.3 ng/ml; p = 0.01, respectively). There were no correlations of analyzed adipokines with COVID-19 severity based on the presence of pneumonia, dyspnea, or necessity of Intensive Care Unit hospitalization (ICU). Liver test abnormalities did not influence adipokines levels. Elevated GGT activity was associated with ICU admission, presence of pneumonia and elevated concentrations of CRP, ferritin and interleukin 6. Chemerin and omentin depletion in COVID-19 patients suggests that this adipokines deficiency play influential role in disease pathogenesis. However, there was no relationship between lower adipokines level and frequency of COVID-19 symptoms as well as disease severity. The only predictive factor which could predispose to a more severe COVID-19 course, including the presence of pneumonia and ICU hospitalization, was GGT activity.

Fetuin-A Deficiency but Not Pentraxin 3, FGF-21, or Irisin, Predisposes to More Serious COVID-19 Course.

Analysis of liver biopsy specimens showed that SARS-CoV-2 might have led to liver damage. This study aimed to evaluate the role of selected hepatokines and myokines in the development and progression of COVID-19. Seventy patients with laboratory-confirmed COVID-19 and 20 healthy volunteers were enrolled in the study. Irisin, pentraxin 3, fetuin-A, and FGF-21 serum concentrations and biochemical parameters were assessed using an immunoenzymatic method with commercially available enzyme immunoassay (EIA) or enzyme-linked immunosorbent assay (ELISA) kits. Serum fetuin-A concentrations were significantly decreased in COVID-19 patients compared to healthy volunteers. The serum concentration of FGF-21 was significantly increased in obese COVID-19 patients compared to overweight ones. Moreover, the FGF-21 level was higher in COVID-19 patients diagnosed with metabolic syndrome than in patients without metabolic syndrome. PTX3 concentration was higher in COVID-19 patients with higher HOMA-IR values than those with lower HOMA-IR values. COVID-19 patients with HOMA-IR ≤ 3 and >3 had significantly lower fetuin-A levels than the control group. Irisin concentration was significantly decreased in the HOMA-IR ≤ 3 COVID-19 subgroup when comparing with the control group. Lower levels of fetuin-A observed in COVID-19 patients despite higher HOMA-IR, CRP, and ferritin levels, pneumonia, patients requiring ICU care suggests that fetuin-A deficiency predisposes to more severe COVID-19 course. Upregulated pentraxin 3 may be used as a potential predictor of COVID-19 severity.

Diagnostic Significance of Serum Galectin-3 in Hospitalized Patients with COVID-19-A Preliminary Study.

Severe coronavirus disease 2019 (COVID-19) is associated with hyperinflammation leading to organ injury, including respiratory failure. Galectin-3 was implicated in innate immunological response to infections and in chronic fibrosis. The aim of our preliminary study was the assessment of the diagnostic utility of serum galectin-3 in patients with COVID-19. The prospective observational study included adult patients admitted with active COVID-19 and treated in tertiary hospital between June and July 2020. The diagnosis was confirmed by the quantitative detection of nucleic acid of severe acute respiratory syndrome coronavirus 2 in nasopharyngeal swabs. Galectin-3 was measured by enzyme immunoassay in serum samples obtained during the first five days of hospital stay. We included 70 patients aged 25 to 73 years; 90% had at least one comorbidity. During the hospital stay, 32.9% were diagnosed with COVID-19 pneumonia and 12.9% required treatment in the intensive care unit (ICU). Serum galectin-3 was significantly increased in patients who developed pneumonia, particularly those who required ICU admission. Positive correlations were found between galectin-3 and inflammatory markers (interleukin-6, C-reactive protein, ferritin, pentraxin-3), a marker of endothelial injury (soluble fms-like tyrosine kinase-1), and a range of tissue injury markers. Serum galectin-3 enabled the diagnosis of pneumonia with moderate diagnostic accuracy and the need for ICU treatment with high diagnostic accuracy. Our findings strengthen the hypothesis that galectin-3 may be involved in severe COVID-19. Further studies are planned to confirm the preliminary results and to verify possible associations of galectin-3 with long-term consequences of COVID-19, including pulmonary fibrosis.

Is the Activity-Based Anorexia Model a Reliable Method of Presenting Peripheral Clinical Features of Anorexia Nervosa?

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.

Complement Components in the Diagnosis and Treatment after Kidney Transplantation-Is There a Missing Link?

Currently, kidney transplantation is widely accepted as the renal replacement therapy allowing for the best quality of life and longest survival of patients developing end-stage renal disease. However, chronic transplant rejection, recurrence of previous kidney disease or newly acquired conditions, or immunosuppressive drug toxicity often lead to a deterioration of kidney allograft function over time. Complement components play an important role in the pathogenesis of kidney allograft impairment. Most studies on the role of complement in kidney graft function focus on humoral rejection; however, complement has also been associated with cell mediated rejection, post-transplant thrombotic microangiopathy, the recurrence of several glomerulopathies in the transplanted kidney, and transplant tolerance. Better understanding of the complement involvement in the transplanted kidney damage has led to the development of novel therapies that inhibit complement components and improve graft survival. The analysis of functional complotypes, based on the genotype of both graft recipient and donor, may become a valuable tool for assessing the risk of acute transplant rejection. The review summarizes current knowledge on the pathomechanisms of complement activation following kidney transplantation and the resulting diagnostic and therapeutic possibilities.

Urinary NGAL Measured after the First Year Post Kidney Transplantation Predicts Changes in Glomerular Filtration over One-Year Follow-Up.

Currently, serum creatinine and estimated glomerular filtration rate (eGFR) together with albuminuria or proteinuria are laboratory markers used in long-term monitoring of kidney transplant recipients. There is a need for more sensitive markers that could serve as early warning signs of graft dysfunction. Our aim was to assess the urinary concentrations of neutrophil gelatinase-associated lipocalin (NGAL) as a predictor of changes in kidney transplant function after the first year post-transplantation. We prospectively recruited 109 patients with functioning graft at least one year after the transplantation, with no acute conditions over the past three months, during their control visits in kidney transplant ambulatory. Urinary NGAL measured on recruitment was twice higher in patients with at least 10% decrease in eGFR over 1-year follow-up compared to those with stable or improving transplant function. Baseline NGAL significantly predicted the relative and absolute changes in eGFR and the mean eGFR during the follow-up independently of baseline eGFR and albuminuria. Moreover, baseline NGAL significantly predicted urinary tract infections during the follow-up, although the infections were not associated with decreasing eGFR. Additionally, we assessed urinary concentrations of matrix metalloproteinase 9-NGAL complex in a subgroup of 77 patients and found higher levels in patients who developed urinary tract infections during the follow-up but not in those with decreasing eGFR. High urinary NGAL in clinically stable kidney transplant recipients beyond the first year after transplantation may be interpreted as a warning and trigger the search for transient or chronic causes of graft dysfunction, or urinary tract infection.

The Marker of Tubular Injury, Kidney Injury Molecule-1 (KIM-1), in Acute Kidney Injury Complicating Acute Pancreatitis: A Preliminary Study.

Acute pancreatitis (AP) may be associated with severe inflammation and hypovolemia leading to organ complications including acute kidney injury (AKI). According to current guidelines, AKI diagnosis is based on dynamic increase in serum creatinine, however, creatinine increase may be influenced by nonrenal factor and appears late following kidney injury. Kidney injury molecule-1 (KIM-1) is a promising marker of renal tubular injury and it has not been studied in AP. Our aim was to assess if urinary KIM-1 may be used to diagnose AKI complicating the early stage of AP. We recruited 69 patients with mild to severe AP admitted to a secondary care hospital during the first 24 h from initial symptoms of AP. KIM-1 was measured in urine samples collected on the day of admission and two subsequent days of hospital stay. AKI was diagnosed based on creatinine increase according to Kidney Disease: Improving Global Outcomes 2012 guidelines. Urinary KIM-1 on study days 1 to 3 was not significantly higher in 10 patients who developed AKI as compared to those without AKI and did not correlate with serum creatinine or urea. On days 2 and 3, urinary KIM-1 correlated positively with urinary liver-type fatty acid-binding protein, another marker of tubular injury. On days 2 and 3, urinary KIM-1 was higher among patients with systemic inflammatory response syndrome, and several correlations between KIM-1 and inflammatory markers (procalcitonin, urokinase-type plasminogen activator receptor, C-reactive protein) were observed on days 1 to 3. With a limited number of patients, our study cannot exclude the diagnostic utility of KIM-1 in AP, however, our results do not support it. We hypothesize that the increase of KIM-1 in AKI complicating AP lasts a short time, and it may only be observed with more frequent monitoring of the marker. Moreover, urinary KIM-1 concentrations in AP are associated with inflammation severity.

Pretreatment with Warfarin Attenuates the Development of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats.

In acute pancreatitis (AP), pancreatic damage leads to local vascular injury, manifesting as endothelial damage and activation, increased vascular permeability, leukocyte rolling, sticking and transmigration to pancreatic tissue as well as activation of coagulation. Previous studies have shown that pretreatment with heparin or acenocoumarol inhibits the development of AP. The aim of the present study was to check the impact of pretreatment with warfarin, an oral vitamin K antagonist, on the development of ischemia/reperfusion-induced AP in rats. AP was induced by pancreatic ischemia followed by reperfusion of the gland. Warfarin (90, 180 or 270 µg/kg/dose) or vehicle were administered intragastrically once a day for 7 days before induction of AP. The effect of warfarin on the severity of AP was assessed 6 h after pancreatic reperfusion. The assessment included histological, functional, and biochemical analyses. Pretreatment with warfarin given at a dose of 90 or 180 µg/kg/dose increased the international normalized ratio and reduced morphological signs of pancreatic damage such as pancreatic edema, vacuolization of acinar cells, necrosis and the number of hemorrhages. These effects were accompanied by an improvement of pancreatic blood flow and a decrease in serum level amylase, lipase, pro-inflammatory interleukin-1ß and plasma level of D-dimer. In contrast, pretreatment with warfarin given at a dose of 270 µg/kg/dose led to an increase in severity of pancreatic damage and biochemical indicators of AP. In addition, this dose of warfarin resulted in deaths in some animals. Pretreatment with low doses of warfarin inhibits the development of AP induced by pancreatic ischemia followed by reperfusion.

Evaluation of Proinflammatory, NF-kappaB Dependent Cytokines: IL-1α, IL-6, IL-8, and TNF-α in Tissue Specimens and Saliva of Patients with Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a life-threatening disease. It could be preceded by oral potentially malignant disorders (OPMDs). It was confirmed that chronic inflammation can promote carcinogenesis. Cytokines play a crucial role in this process. The aim of the study was to evaluate interleukin-1alpha (IL-1α), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-α) in tissue specimens and saliva of patients with OSCC and OPMDs. METHODS: Cytokines were evaluated in 60 tissue specimens of pathological lesions (OSCCs or OPMDs) and in 7 controls (normal oral mucosa, NOM) by immunohistochemistry and in saliva of 45 patients with OSCC or OPMDs and 9 controls (healthy volunteers) by enzyme-linked immunosorbent assays. RESULTS: Immunohistochemical analysis revealed significantly higher expression of IL-8 in OSCC specimens and TNF-α in OSCCs and OPMDs with dysplasia as compared to NOM. Moreover, expression of TNF-α was significantly higher in oral leukoplakia and oral lichen planus without dysplasia, whereas expression of IL-8 only in oral leukoplakia without dysplasia in comparison with NOM. Salivary concentrations of all evaluated cytokines were significantly higher in patients with OSCC than in controls. Moreover, levels of IL-8 were significantly higher in saliva of patients with OPMDs with dysplasia as compared to controls and in OSCC patients as compared to patients with dysplastic lesions. There was also significant increase in salivary concentrations of IL-6, IL-8 and TNF-α in patients with OSCC as compared to patients with OPMDs without dysplasia. CONCLUSION: The study confirmed that proinflammatory, NF-kappaB dependent cytokines are involved in pathogenesis of OPMDs and OSCC. The most important biomarker of malignant transformation process within oral mucosa among all assessed cytokines seems to be IL-8. Further studies on a larger sample size are needed to corroborate these results.

Acute Phase Proteins and Vitamin D Seasonal Variation in End-Stage Renal Disease Patients.

End-stage renal disease (ESRD) patients are vulnerable to vitamin D deficiency due to impaired renal hydroxylation, low dietary intake and inadequate sun exposure. Vitamin D plays a role in innate and adaptive immunity and its seasonal variation has been linked to mortality. ESRD is associated with inadequate removal of pro-inflammatory cytokines regulating acute phase protein (APP) synthesis. Our aim was to look for associations between lifestyle factors, diet, and vitamin D seasonal variation and their relationship with selected APPs and calcium-phosphate metabolism. The study included 59 ESRD patients treated with maintenance hemodialysis. A 24-hour dietary recall was conducted in the post-summer (November 2018, PS) and post-winter (February/March 2019, PW) period, and blood was collected for the measurements of serum total vitamin D, α1-acid glycoprotein (AGP), C-reactive protein (CRP), albumin, prealbumin (PRE), parathormone, calcium and phosphate. A self-constructed questionnaire gathered information on vitamin D supplementation, sun exposure and physical activity. Higher caloric intake was observed PW compared PS. Less than 15% of participants met the dietary recommendations for energy, protein, fiber, vitamin D and magnesium intake. Vitamin D supplementation was associated with higher serum vitamin D regardless of season. AGP, PRE, albumin, and vitamin D presented seasonal changes (higher values PS). In patients with serum vitamin D below 25 ng/mL, vitamin D seasonal change correlated with CRP and prealbumin change. Phosphate and Ca × P correlated positively with AGP. A low vitamin D serum level could impact the inflammatory process; however, more studies are needed to confirm the relationship.

Does Beta-Trace Protein (BTP) Outperform Cystatin C as a Diagnostic Marker of Acute Kidney Injury Complicating the Early Phase of Acute Pancreatitis?

Acute pancreatitis (AP) belongs to the commonest acute gastrointestinal conditions requiring hospitalization. Acute kidney injury (AKI) often complicates moderately severe and severe AP, leading to increased mortality. Among the laboratory markers proposed for early diagnosis of AKI, few have been studied in AP, including cystatin C and neutrophil gelatinase-associated lipocalin (NGAL). Beta-trace protein (BTP), a low-molecular-weight glycoprotein proposed as an early marker of decreased glomerular filtration, has never been studied in AP. We investigated the diagnostic usefulness of serum BTP for early diagnosis of AKI complicating AP in comparison to previously studied markers. BTP was measured in serum samples collected over the first three days of hospital stay from 73 adult patients admitted within 24 h of mild to severe AP. Thirteen patients (18%) developed AKI in the early phase of AP. Serum BTP was higher in patients who developed AKI, starting from the first day of hospitalization. Strong correlations were observed between BTP and serum cystatin C but not serum or urine NGAL. On admission, BTP positively correlated with endothelial dysfunction. The diagnostic usefulness of BTP for AKI was similar to cystatin C and lower than NGAL. Increased BTP is an early predictor of AKI complicating AP. However, it does not outperform cystatin C or NGAL.