An exocyclic π-system extension of the phenanthriporphyrin framework: towards azaaceneporphyrinoids

International audienceAn exocyclic π-extension of phenanthriporphyrin reduces the macrocyclic antiaromaticity of the formed expanded carbaporphyrinoids

Ocena stanu antyoksydacyjnego w wybranych chorobach układowych tkanki łącznej

INTRODUCTION: Reactive oxygen species (ROS), which cause increased degradation of nitric oxide and defects in endothelial function, play an essential role in the pathogenesis of increased vascular contractility. Reactive oxygen species are produced in the vascular bed by endothelial cells, smooth muscle cells and fibroblasts. The destructive effect of ROS is of great importance to the pathogenesis of many diseases such as atheromatosis, ischemia, heart fail-ure, cerebral insufficiency and respiratory failure. MATERIAL AND METHODS: A total of 36 patients (31 females, 5 males; mean age 47 ± 7 years) with connective tissue diseases (systemic lupus erythematosus – 23 patients, systemic sclerosis – 13 patients) and 40 (37 females, 3 males) healthy volunteers (mean age 50 ± 2 years) of both sexes were enrolled in the study. This study evaluated the total antioxidant capacity in serum, using the method of reducing radical DPPH and radical ABTS•+. RESULTS: The blood plasma of the patients had lower antioxidant activities compared to the blood plasma of the healthy controls. CONCLUSIONS: This study shows the differences in the antioxidant activity in healthy volunteers and patients with connective tissue diseases. These parameters can be monitored during treatment by modulating oxidative metabolism and by stimulating antioxidant activity.WSTĘP: Reaktywne formy tlenu zwiększają degradację tlenku azotu i upośledzają funkcję śródbłonka, odgrywają ponadto istotną rolę w patogenezie zwiększonej kurczliwości naczyń. Produkowane są przez komórki śródbłonka łożyska naczyniowego, komórki mięśni gładkich oraz fibroblasty. Destrukcyjny wpływ reaktywnych form tlenu ma duże znaczenie w patogenezie wielu chorób, takich jak: miażdżyca, niedokrwienie, niewydolność serca, niewydolność naczyń mózgowych oraz niewydolność oddechowa. MATERIAŁ I METODY: W grupie badanej było 36 pacjentów (31 kobiet i 5 mężczyzn; średnia wieku 47 ± 7 lat) z chorobą tkanki łącznej (23 osoby z toczniem rumieniowatym układowym oraz 13 osób z twardziną układową), w grupie kontrolnej 40 zdrowych ochotników (37 kobiet i 3 mężczyzn; średnia wieku 50 ± 2 lata). W pracy oceniono całkowitą zdolność antyoksydacyjną w surowicy, wykorzystując metodę redukcji rodnika DPPH i rodnika ABTS•+. WYNIKI: U pacjentów z chorobą układową tkanki łącznej aktywność antyoksydacyjna osocza jest mniejsza w porównaniu z grupą zdrowych ochotników. WNIOSKI: W pracy wykazano różnice w aktywności antyoksydacyjnej między zdrowymi ochotnikami a pacjentami z chorobą tkanki łącznej. Parametry te mogą być monitorowane podczas terapii przez modulowanie metabolizmu oksydacyjnego i stymulację aktywności antyoksydantów

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

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