Jacek Czepiel

Lyme disease: review.

Lyme disease is a multi-organ animal-borne disease, caused by spirochetes of Borrelia burgdorferi (Bb), which typically affect the skin, nervous system, musculoskeletal system and heart. A history of confirmed exposure to tick bites, typical signs and symptoms of Lyme borreliosis and positive tests for anti-Bb antibodies, are the basis of a diagnosis. A two-step diagnosis is necessary: the first step is based on a high sensitivity ELISA test with positive results confirmed by a more specific Western blot assay. Antibiotic therapy is curative in most cases, but some patients develop chronic symptoms, which do not respond to antibiotics. The aim of this review is to summarize our current knowledge of the symptoms, clinical diagnosis and treatment of Lyme borreliosis.

WSES guidelines for management of Clostridium difficile infection in surgical patients

In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients.

n-3 Fatty acids as resolvents of inflammation in the A549 cells

BACKGROUND Fatty acids and their derivatives are one of the most crucial inflammation mediators. The aim of our study was to evaluate the impact of polyunsaturated fatty acids as eicosanoids precursors on the A549 cell line. METHODS Cells were incubated with 40 μM of arachidonic, eicosapentaenoic or docosahexaenoic acid for 24h, then activated with LPS. Fatty acids content in the cell membranes were determined using gas chromatography. COX-2, cPGES and FP-receptor quantities were determined by Western blot. 8-Isoprostane F2α concentrations were determined by EIA. Maresin and protectin D1 contents were analyzed by UHPLC/MS-TOF method. RESULTS Significant differences in membrane fatty acids and levels of 8-isoPGF2α in the activated cells were detected. Elevated expression of COX-2 and FP-receptor was observed in cells treated with AA and activated with LPS. Moreover, compared to AA and AA+LPS groups, cells incubated with EPA, DHA, EPA+LPS and DHA+LPS showed decreased expression of COX-2, cPGES and FP-receptor. In cells incubated with EPA or DHA and activated with LPS maresin and protectin D1 were detected. CONCLUSIONS The results of the study have revealed the pro-inflammatory properties of AA, while the EPA and DHA had the opposite, resolving effect. Interestingly, FP-receptor inhibition by EPA and DHA demonstrated the unique role of the FP-receptor as a potential target for antagonists, in the diseases of inflammatory character. This study provides new information about n-3 fatty acids and their pro-resolving mediators, which can be used in the process of developing new anti-inflammatory drugs.

Erythrocyte membrane fatty acids in multiple myeloma patients

Mounting data show that fatty acids (FA) and fatty acid synthase (FAS) function could be potential targets for multiple myeloma (MM) therapy. Our study aimed at comparing the FA composition of erythrocyte membranes of MM patients and healthy controls. MM patients had higher saturated FA and n-6 polyunsaturated FA (PUFA) and lower monounsaturated, n-3 PUFA and trans-FA indices than controls. The n-3/n-6 PUFA ratio was lower in MM patients and there was distinct clustering of variants of individual FA in MM patients. The FA content of erythrocyte membrane could serve as a diagnostic and/or predictive biomarker in MM.

Plasma fatty acid profile in multiple myeloma patients

New membrane formation in the proliferating tumor cells consequently results in hypermetabolism of fatty acids (FA), as seen in many cancer patients, including multiple myeloma (MM). The FA composition of plasma reflects both endogenous synthesis as well as the dietary supply of these compounds. Additionally, obesity is a risk factor for the development of MM. The aim of this study was to compare the FA composition of plasma in 60 MM patients and 60 healthy controls. We noted significant differences in the FA profile of plasma from patients with MM when compared to the control group. Increased levels of saturated and n-6 polyunsaturated fatty acids in MM patients suggest that there may be increased endogenous synthesis of these fatty acids, likely due to increased expression of desaturase and elongase. Furthermore, cluster analysis showed differences in the distribution of FA in plasma from MM patients compared to controls. Dietary fat and a deranged endogenous FA metabolism may contribute to cancer-associated inflammation through an abnormal arachidonic acid metabolism, caused by pro-inflammatory derivatives. Our study supports further research on the biochemistry of lipids in patients with MM.

Central nervous system involvement by multiple myeloma: A multi-institutional retrospective study of 172 patients in daily clinical practice

The multicenter retrospective study conducted in 38 centers from 20 countries including 172 adult patients with CNS MM aimed to describe the clinical and pathological characteristics and outcomes of patients with multiple myeloma (MM) involving the central nervous system (CNS). Univariate and multivariate analyses were performed to identify prognostic factors for survival. The median time from MM diagnosis to CNS MM diagnosis was 3 years. Thirty‐eight patients (22%) were diagnosed with CNS involvement at the time of initial MM diagnosis and 134 (78%) at relapse/progression. Upon diagnosis of CNS MM, 97% patients received initial therapy for CNS disease, of which 76% received systemic therapy, 36% radiotherapy and 32% intrathecal therapy. After a median follow‐up of 3.5 years, the median overall survival (OS) from the onset of CNS involvement for the entire group was 7 months. Untreated and treated patients had median OS of 2 and 8 months, respectively (P < 0.001). At least one previous line of therapy for MM before the diagnosis of CNS disease and >1 cytogenetic abnormality detected by FISH were independently associated with worse OS. The median OS for patients with 0, 1 and 2 of these risk factors were 25 months, 5.5 months and 2 months, respectively (P < 0.001). Neurological manifestations, not considered chemotherapy‐related, observed at any time after initial diagnosis of MM should raise a suspicion of CNS involvement. Although prognosis is generally poor, the survival of previously untreated patients and patients with favorable cytogenetic profile might be prolonged due to systemic treatment and/or radiotherapy. Am. J. Hematol. 91:575–580, 2016.

HGF, sIL-6R and TGF-β1 Play a Significant Role in the Progression of Multiple Myeloma.

Background. In the last few years, it has been widely reported that proinflammatory and angiogenic cytokines are important for the development and progression of multiple myeloma (MM). Objectives. To further validate and acquire more insight into this view we decided to check whether plasma levels of certain cytokines and their soluble receptors differ between MM patients and healthy subjects. Patients and Methods. The study was conducted in 76 MM patients aged 22 to 77 years (60±10 years) and 35 healthy controls aged 20 to 63 years (33±10 years). Plasma levels of interleukin-6 (IL-6), b-fibroblast growth factor (b-FGF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1), as well as soluble receptors for IL-6 (sIL-6R) and VEGF (sVEGF-R2) were measured using enzyme-linked immunosorbent assay (ELISA). Results. Significantly higher plasma levels of IL-6 (13.65±42.61 vs. 1.04±1.12 pg/ml, p=0.006), HGF (2174±2714 vs. 648±130 pg/ml, p<0.001), b-FGF (7.92±10.78 vs. 2.54±5.38 pg/ml, p<0.001) and sIL-6R (37.1±14.2 vs. 25.3±6.4 ng/ml, p=0.003) were observed in MM patients vs. healthy controls, respectively. Plasma sVEGF-R2 was significantly lower in MM patients than in controls (7518±2119 vs. 8725±1281 pg/ml, respectively; p<0.001). We observed an inverse correlation between length of treatment and the level of sIL-6R, and TGF-β1 in plasma. Conclusions. Plasma levels of HGF, b-FGF, IL-6 and sIL-6R in MM patients were higher when compared to the control group. Antineoplastic therapy leads to a time-dependent decrease in plasma levels of sIL-6R, and TGF-β1 in MM patients. Blood plasma level of HGF is an optimal measure to differentiate patients in whom disease is progressing versus patients who respond to therapy.

n-3 Fatty acids regulate the inflammatory-state related genes in the lung epithelial cells exposed to polycyclic aromatic hydrocarbons

BACKGROUND Chronic airway inflammation is coordinated by a complex of inflammatory mediators, including eicosanoids. The aim of this study was to evaluate the impact of polycyclic aromatic hydrocarbons (PAHs) on the human lung epithelial carcinoma A549 cells supplemented with docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids. METHODS We analyzed the influence of DHA, EPA and/or benzo(a)pyrene (BaP), chrysene (Chr), fluoranthene (Flu) and benzo(a)anthracene (Baa) treatment on the fatty acids (FAs) profile and the formation of isoprostanes. We studied the cyclooxygenase-2, FP-receptor, peroxisome proliferator-activated receptors PPARδ and PPARγ, transcription factor NF-кB p50 and p65 expression by Western blot, phospholipase A2 (cPLA2) activity, as well as aryl hydrocarbon receptor (AHR), cytochrome P450 (CYP1A1), phospholipase A2 (PLA2G4A) and prostaglandin synthase 2 (PTGS2) gene expression by qRT-PCR. RESULTS DHA or EPA supplementation and BaP or Baa treatment resulted in a higher level of PGF3α. COX-2 expression was decreased while PPARδ expression and cPLA2 activity was increased after fatty acid supplementation and PAHs treatment. DHA and EPA up-regulated AHR and PLA2G4A genes. CONCLUSIONS Supplementation with n-3 FAs resulted in changes of inflammatory-state related genes in the lung epithelial cells exposed to PAHs. The altered profile of lipid mediators from n-3 FA as well as repression of the COX-2 protein by n-3 PUFAs in A549 cells incubated with PAHs suggests anti-inflammatory and pro-resolving properties of DHA and EPA. It remains to be shown whether these pleiotropic and protective actions of n-3 FAs contribute to fish oils therapeutic effect in asthma.

Docosahexaenoic acid regulates gene expression in HUVEC cells treated with polycyclic aromatic hydrocarbons.

The molecular mechanism of inflammation and carcinogenesis induced by exposure of polycyclic aromatic hydrocarbons (PAHs) is not clearly understood. Our study was undertaken due to the strong pro-carcinogenic potential and reactivity of PAH-metabolites, as well as the susceptibility of polyunsaturated fatty acids to oxidation. The aim of this study was to evaluate the pro- or anti-inflammatory impact of n-3 docosahexaenoic acid on human primary umbilical vein endothelial cells (HUVEC) exposed to polycyclic aromatic hydrocarbons. We analysed the influence of docosahexaenoic acid (DHA) and/or PAHs supplementation on the fatty acid profile of cell membranes, on cyclooxygenase-2 (COX-2), aryl hydrocarbon receptor (AHR), and glutathione S transferase Mu1 (GSTM1) protein expression as well as on the prostaglandin synthase 2 (PTGS2), AHR, GSTM1, PLA2G4A, and cytochrome P450 CYP1A1 gene expression. We observed that COX-2 and AHR protein expression was increased while GSTM1 expression was decreased in cells exposed to DHA and PAHs. Docosahexaenoic acid down-regulated CYP1A1 and up-regulated the AHR and PTGS2 genes. Our findings suggested that DHA contributes significantly to alleviate the harmful effects caused by PAHs in endothelial cells. Moreover, these results suggest that a diet rich in n-3 fatty acids is helpful to reduce the harmful effects of PAHs exposure on human living in heavily polluted areas.

The Analysis of the Relationship between Multiple Myeloma Cells and Their Microenvironment.

The bone marrow microenvironment plays a key role in the stimulation of growth and survival of multiple myeloma (MM) cells. We investigated whether membrane microfragments (MFBs) exert a stimulatory effect on mesenchymal stem cell (MSC) gene expression or differentiation. MSCs from patients with multiple myeloma (MMBM-MSCs) proliferated at a slower rate than MSCs from healthy volunteers (BM-MSCs), and fewer MMBM-MSCs adhered to the substrate as compared to BM-MSCs. Phenotypic analysis revealed that MMBM-MSCs and BM-MSCs differed significantly in terms of their CD166 and CXCR4 expressions. In conclusion, our comparative analysis of mesenchymal cells from MM patients and healthy volunteers revealed differences in the genetic and phenotypic profiles of these two populations, their potential for osteodifferentiation, and expression of surface antigens. Moreover, we showed that membrane MFBs may alter the genetic profile of MSCs, leading to disorders of their osteodifferentiation, and interact with the WNT pathway via presentation of the DKK-1 protein.