Towards the Application of Atorvastatin to Intensify Proapoptotic Potential of Conventional Antileukemic Agents In Vitro

It has been previously revealed that statins used at high concentrations display antileukemic potential towards chronic lymphocytic leukemia (CLL) cells. However, their usage alone in clinical practice may be limited due to possible side effects of high doses of these drugs. On the other hand, combined treatment of leukemia with statins and the conventional chemotherapeutics is questionable because of unknown influence of the first on the standard treatment results. This study has revealed that in vitro atorvastatin increases the proapoptotic potential of cladribine and mafosfamide in CLL cells isolated from peripheral blood of patients. Moreover, a preincubation with the above statin sensitizes leukemic cells to CM-induced apoptosis even at small concentrations of the drug. The usage of atorvastatin together with or followed by the conventional chemotherapy should be considered as therapeutic option for the treatment for this leukemia. Interestingly, CM-resistant patients might have the biggest benefits from atorvastatin administration.Grant no. 1407 from the University of Łódź

Health behaviors of patients after breast cancer surgery in the Podkarpackie voivodeship

Aim. An evaluation of lifestyle changes (physical activity, diet) in patients after breast cancer surgery. Materials and method. 200 women after breast cancer surgery were surveyed. The respondents were asked whether the surgery caused a change in their diet and physical activity. An analysis was performed concerning the education, place of residence and age of the respondents. Results. Prior to being diagnosed with breast cancer, about one third of the respondents were concerned about their diet and physical activity. After the surgery more than a half of the respondents were concerned about a healthy lifestyle. Women below 50 years old with higher education, who live in a city, were concerned about their diet and physical activity both before and after surgery. Conclusions. As a result of the breast cancer surgery, lifestyle changes were most often found in women aged 50-69 years old with higher education who lived in a city. Statistical relevance of the results was noted

Efekty hemodynamiczne etomidatu, propofolu i elektrowstrząsu u chorych poddawanych testowaniu kardiowertera-defibrylatora

Background: Anaesthetic drugs and internal electrical shock may alter the haemodynamic status of patients undergoing implantable cardioverter-defibrillator (ICD) testing. Comparative data on the mechanisms of etomidate and propofol-induced changes in haemodynamic parameters are inconsistent. Also the effects of ICD shock on haemodynamics have not been extensively studied. Aim: To compare the haemodynamic effects of etomidate and propofol as well as electrical shock during ICD testing in a prospective, randomised trial. Methods: The study group consisted of 63 consecutive patients (mean age 66 ± 10 years, 51 males) who underwent ICD testing. Haemodynamic parameters were measured using impedance cardiography (Task Force Monitor Systems, CNSystems, Austria) before and after injection of etomidate (n = 30) or propofol (n = 33) as well as immediately after internal defibrillation of ventricular fibrillation (VF). Parameters measured included heart rate, systolic (sBP), diastolic (dBP) and mean (mBP) blood pressure, stroke volume (SV), cardiac output (CO) and total peripheral resistance (TPR). Results: Propofol significantly decreased the values of all measured parameters (sBP: 123.4 ± 17.1 vs. 106.3 ± 18 mm Hg, p < 0.0001; dBP: 83.7 ± 12.2 vs. 74.1 ± 13.8 mm Hg, p < 0.0001; mBP: 93.9 ± 13.1 vs. 81.1 ± 16.1 mm Hg, p < 0.0001; SV: 61.1 ± 19.3 vs. 56.4 ± 15.7 mL, p < 0.003; CO: 4.51 ± 1.07 vs. 4.17 ± 0.73 L/min, p < 0.003; and TPR: 1,735.8 ± 532.6 vs. 1,573.9 ± 390.5 dyn×s/cm5), whereas the only significant change following etomidate infusion was a decrease in SV (60.6 ± 11 vs. 56.8 ± 10 mL, p < 0.022). The propofol-induced changes were similar in patients with reduced (< 40%) vs. preserved (≥ 40%) left ventricular ejection fraction (LVEF) and in patients in heart failure NYHA class 0–II vs. class III–IV. Induction of VF and internal electrical shock did not cause major haemodynamic changes apart from significant, albeit very modest, drops in dBP and mBP (77 ± 2 vs. 72.9 ± 18 mm Hg, p < 0.002, and 85.2 ± 17 vs. 81.8 ± 20 mm Hg, p < 0.017, respectively). There were no complications during ICD testing. Conclusions: Propofol significantly decreased BP probably by both reducing CO and causing vasodilatation, whereas etomidate only slightly decreased dBP and mBP without affecting other parameters. Propofol-induced changes were independent of LVEF or NYHA class. Induction of VF and internal defibrillation did not cause clinically significant changes apart from very modest drops in dBP and mBP values. Wstęp: Leki anestetyczne i indukcja migotania komór (VF) oraz następowy elektrowstrząs mogą ujemnie wpływać na stan hemodynamiczny chorych, u których testuje się skuteczność kardiowertera-defibrylatora (ICD). Mechanizmy oddziaływania na parametry hemodynamiczne (ujemny efekt inotropowy vs. wazodylatacja) etomidatu i propofolu nie są do końca zbadane, podobnie jak skutki hemodynamiczne indukcji VF i następowego wyładowania z ICD. Kardiografia impedancyjna nie była jeszcze używana do oceny skutków działania leków anestetycznych. Cel: Celem pracy było porównanie efektów hemodynamicznych etomidatu i propofolu oraz wywołania VF i następowego elektrowstrząsu u chorych z ICD. Metody: Do prospektywnego badania z randomizacją włączono 63 kolejnych chorych (średni wiek 66 ±10 lat, 51 mężczyzn) poddawanych testowaniu skuteczności ICD. Parametry hemodynamiczne mierzono przy użyciu kardiografii impedancyjnej (Task Force Monitor Systems, CNSystems, Austria) przed i po podaniu etomidatu (n = 30) lub propofolu (n = 33) oraz natychmiast po elektrowstrząsie przerywającym wyindukowane VF. Rejestrowano ciśnienie skurczowe (sBP), rozkurczowe (dBP) i średnie (mBP), pojemność wyrzutową (SV), rzut serca (CO) i całkowity opór obwodowy (TPR). Wyniki: Propofol istotnie obniżył wszystkie mierzone parametry (sBP: 123,4 ± 17,1 vs. 106,3 ± 18 mm Hg; p < 0,0001; dBP: 83,7 ± 12,2 vs. 74,1 ± 13,8 mm Hg; p < 0,0001; mBP: 93,9 ± 13,1 vs. 81,1 ± 16,1 mm Hg; p < 0,0001; SV: 61,1 ± 19,3 vs. 56,4 ± 15,7 ml; p < 0,003; CO: 4,51 ± 1,07 vs. 4,17 ± 0,73 l/min; p < 0,003; TPR: 1735,8 ± 532,6 vs. 1573,9 ± 390,5 dyn × s/cm5), podczas gdy etomidat obniżył istotnie jedynie SV (60,6 ± 11 vs. 56,8 ± 10 ml; p < 0,022). Zmiany hemodynamiczne po propofolu były podobne u chorych z obniżoną (< 40%) i zachowaną (≥ 40%) frakcją wyrzutową lewej komory oraz u osób z różnym stopniem niewydolności serca (NYHA I–II vs. III–IV) (NS). Wywołanie VF i elektrowstrząs z ICD nie spowodowały wyraźnych zmian hemodynamicznych poza istotnym statystycznie, ale niewielkim spadkiem dBP i mBP (odpowiednio, 77 ± 2 vs. 72,9 ± 18 mm Hg; p < 0,002 i 85,2 ± 17 vs. 81,8 ± 20 mm Hg; p < 0,017). Podczas testowania ICD nie stwierdzono żadnych powikłań. Wnioski: Propofol istotnie obniżył ciśnienie tętnicze prawdopodobnie zarówno poprzez zmniejszenie SV, jak i wazodylatację (obniżenie TPR), niezależnie od stopnia niewydolności serca lub uszkodzenia lewej komory. Po etomidacie pogorszenie parametrów hemodynamicznych było znacznie mniejsze, co potwierdza tendencję do preferowania tego leku w stosunku do propofolu u chorych niestabilnych hemodynamicznie lub z niskim ciśnieniem. Indukcja VF i elektrowstrząs nie wpłynęły istotnie na hemodynamikę układu sercowo-naczyniowego.

Selected issues related to the use of firearms for unlawful killing of animals

Zagadnienie badania pośmiertnego zwierząt, których śmierć nastąpiła wskutek doznanych ran postrzałowych, jest w literaturze podejmowane bardzo rzadko, najczęściej przy okazji badania i opisywania innych problemów. Niniejszy artykuł jest próbą zebrania dotychczasowych osiągnięć weterynarii sądowej w tym zakresie. Jako punkt wyjścia omawianych zagadnień przyjęto aktualną regulację prawną, wskazując na sankcje karne wynikające z nielegalnego użycia broni w stosunku do zwierząt. Następnie przedstawiono możliwości wykorzystania nowoczesnych technik obrazowych w badaniach pośmiertnych prowadzonych przez lekarzy weterynarii na zlecenie organów ścigania. Omawiane doniesienia naukowe wzbogacone zostały przykładami badań sekcyjnych wykonywanych na zlecenie organów ścigania w polskich placówkach naukowych. W artykule wskazano, że wyniki badania ran postrzałowych doznanych przez ludzi w różnych okolicznościach mogą być wykorzystywane w opiniowaniu sądowo-weterynaryjnym, podobnie jak wyniki badań ran postrzałowych dużych ssaków mogą być pomocne przy badaniu skutków obrażeń postrzałowych u ludzi.The issue of post-mortem examination of animals, whose death occurred as a result of suffered gunshot wounds, is very rarely discussed in literature, most often on the occasion of researching into and describing other problems. This article presents an attempt to bring together the achievements of veterinary forensics in this area. As a starting point, the current legal regulation was adopted, pointing to penal sanctions resulting from the illegal use of weapons in relation to animals. Subsequently, the possibilities of using modern imaging techniques in post-mortem examinations carried out by veterinarians at the request of law enforcement agencies were presented. The scientific reports discussed herein have been supplemented by examples of sectional examinations carried out at the request of law enforcement agencies in Polish scientific institutions. The article indicates that the results of examination of gunshot wounds suffered by people in various circumstances may be used for the purpose of issuing forensic veterinary opinions, just as the results of examination of gunshot wounds of large mammals may be helpful in examining the effects of gunshot injuries in humans

Prognostic Value of Resistance Proteins in Plasma Cells from Multiple Myeloma Patients Treated with Bortezomib-Based Regimens

While multiple myeloma (MM) treatment with proteasome inhibitors and other agents yields encouraging results, primary and secondary resistance remains an emerging problem. An important factor in such treatment resistance is the overexpression of several proteins. The present study comprehensively evaluates the expression of POMP, PSMB5, NRF2, XBP1, cMAF and MAFb proteins in plasma cells isolated from the bone marrow of 39 MM patients treated with bortezomib-based regimens using an enzyme-linked immunosorbent assay (ELISA). The proteins were selected on the basis of previous laboratory and clinical studies in bortezomib-treated MM patients. It was found that the expression of the investigated proteins did not significantly differ between bortezomib-sensitive and bortezomib-refractory patients. However, the expression of some proteins correlated with overall survival (OS); this was significantly shorter in patients with higher POMP expression (HR 2.8, 95% CI: 1.1–7.0, p = 0.0277) and longer in those with higher MAFB expression (HR 0.32, 95% CI: 0.13–0.80, p = 0.0147). Our results indicate that a high expression of POMP and MAFB in MM plasma cells may serve as predictors of OS in MM patients treated with bortezomib-based regimens. However, further studies are needed to determine the role of these factors in effective strategies for improving anti-myeloma therapy

The Prognostic Value of Whole-Blood PSMB5, CXCR4, POMP, and RPL5 mRNA Expression in Patients with Multiple Myeloma Treated with Bortezomib

Proteasome inhibitors, like bortezomib, play a key role in the treatment of multiple myeloma (MM); however, most patients eventually relapse and eventually show multiple drug resistance, and the molecular mechanisms of this resistance remain unclear. The aim of our study is to assess the expression of previously described genes that may influence the resistance to bortezomib treatment at the mRNA level (ABCB1, CXCR4, MAF, MARCKS, POMP, PSMB5, RPL5, TXN, and XBP1) and prognosis of MM patients. mRNA expression was determined in 73 MM patients treated with bortezomib-based regimens (30 bortzomib-sensitive and 43 bortezomib-refractory patients) and 11 healthy controls. RPL5 was significantly down-regulated in multiple myeloma patients as compared with healthy controls. Moreover, POMP was significantly up-regulated in MM patients refractory to bortezomib-based treatment. In multivariate analysis, high expression of PSMB5 and CXCR and autologous stem cell transplantation were independent predictors of progression-free survival, and high expression of POMP and RPL5 was associated with shorter overall survival

Cytokine and Chemokine Profile in Patients with Multiple Myeloma Treated with Bortezomib

The aim of the study was to determine the levels of selected cytokines and chemokines in the serum of multiple myeloma (MM) patients treated with bortezomib-based regimens. A total of 71 MM patients were examined: 41 with primary refractory disease (17) or early relapse (28), and 30 who were bortezomib sensitive with no progression for at least six months. Patients who demonstrated CR or PR after bortezomib-based therapies longer than six months after treatment discontinuation were designated bortezomib sensitive. Serum cytokine levels were assayed with Bio-Rad Bio-Plex Pro Human Cytokine 27-Plex Assay on the MAGPIX Multiplex Reader and the Bio-Plex® 200 System (Bio-Rad). Higher levels of MIP-1α and lower levels of MIP-1β and IL-9 were associated with better responses to bortezomib-based treatment, and higher levels of IL-1ra and IL-8 were associated with bone involvement. MCP-1 was elevated in patients with hemoglobin<10 g/dl compared to those without anemia. The levels of IL-8, MIP-1α, and TNF-α were significantly higher in patients with renal insufficiency. Only MIP-1α was elevated in patients with hypercalcemia compared to patients with normal calcium levels. In conclusion, distinct cytokines are involved in the pathogenesis of MM and may play a prominent role in the prediction of treatment response. However, a single measurement of serum cytokines should be interpreted with caution and further studies are needed

Table_1_High serum miR-223-3p expression level predicts complete response and prolonged overall survival in multiple myeloma patients undergoing autologous hematopoietic stem cell transplantation.docx

IntroductionAHSCT is the treatment of choice for newly diagnosed patients with transplant-eligible multiple myeloma (MM). However, considerable variability in response to autologous hematopoietic stem cell transplantation (AHSCT) results in only 50% of patients achieving complete response (CR) after AHSCT, which is directly associated with improved progression-free and overall survival (OS). In this study, we aimed to investigate the potential predictive role of selected serum miRNAs in MM patients who underwent AHSCT.Patients and methodsSerum expression level of 6 miRNAs: miR-221-3p, miR-15b-5p, miR-223-3p, miR-320c, miR-361-3p, and miR-150-5p was evaluated in 51 patients who underwent AHSCT. Blood samples were collected at two time points: before conditioning chemotherapy (T1) and fourteen days after transplant (+14) (T2).ResultsAll selected miRNAs significantly changed their expression level across the procedure- two were up-regulated after AHSCT: hsa-miR-320c (FC 1.42, pConclusionSerum expression of has-miR-223-3p is a predictor of CR and prolonged OS in MM patients undergoing AHSCT.</p

DataSheet_3_High serum miR-223-3p expression level predicts complete response and prolonged overall survival in multiple myeloma patients undergoing autologous hematopoietic stem cell transplantation.zip

IntroductionAHSCT is the treatment of choice for newly diagnosed patients with transplant-eligible multiple myeloma (MM). However, considerable variability in response to autologous hematopoietic stem cell transplantation (AHSCT) results in only 50% of patients achieving complete response (CR) after AHSCT, which is directly associated with improved progression-free and overall survival (OS). In this study, we aimed to investigate the potential predictive role of selected serum miRNAs in MM patients who underwent AHSCT.Patients and methodsSerum expression level of 6 miRNAs: miR-221-3p, miR-15b-5p, miR-223-3p, miR-320c, miR-361-3p, and miR-150-5p was evaluated in 51 patients who underwent AHSCT. Blood samples were collected at two time points: before conditioning chemotherapy (T1) and fourteen days after transplant (+14) (T2).ResultsAll selected miRNAs significantly changed their expression level across the procedure- two were up-regulated after AHSCT: hsa-miR-320c (FC 1.42, pConclusionSerum expression of has-miR-223-3p is a predictor of CR and prolonged OS in MM patients undergoing AHSCT.</p