Inhibitory effect of N-ethyl-3-amino-5-oxo-4-phenyl-2,5-dihydro-1H-pyrazole-1-carbothioamide on Haemophilus spp. planktonic or biofilm-forming cells

During this study, we have investigated in vitro activity of N-substituted-3-amino-5-oxo-4-phenyl-2,5-dihydro-1H-pyrazole-1-carbothioamide derivatives with N-ethyl, N-(4-metoxyphenyl) and N-cyclohexyl substituents against Gram-negative Haemophilus influenzae and H. parainfluenzae bacteria. A spectrophotometric assay was used in order to determine the bacterial growth and biofilm formation using a microtiter plate to estimate minimal inhibitory concentration (MIC) and minimal biofilm inhibitory concentration (MBIC). Among the tested N-substituted pyrazole derivatives, only N-ethyl-3-amino-5-oxo-4-phenyl-2,5-dihydro-1H-pyrazole-1-carbothioamide showed a significant in vitro activity against both planktonic cells of H. parainfluenzae (MIC = 0.49–31.25 μg ml^?1) and H. influenzae (MIC = 0.24–31.25 μg ml^?1) as well as biofilm-forming cells of H. parainfluenzae (MBIC = 0.24–31.25 μg ml^?1) and H. influenzae (MBIC = 0.49 to ≥31.25 μg ml^?1). The pyrazole compound exerted higher inhibitory effect both on the growth of planktonic cells and biofilm formation by penicillinase-positive and penicillinase-negative isolates of H. parainfluenzae than the activity of commonly used antibiotics such as ampicillin. No cytotoxicity of the tested compound in vitro at concentrations used was found. The tested pyrazole N-ethyl derivative could be considered as a compound for the design of agents active against both pathogenic H. influenzae and opportunistic H. parainfluenzae, showing also anti-biofilm activity. This appears important because biofilms are determinants of bacterial persistence in long-term and recurrent infections recalcitrant to standard therapy.     

The Effect of the Activation Process and Metal Oxide Addition (CaO,MgO, SrO) on the Catalytic and Physicochemical Properties of Natural Zeolite in Transesterification Reaction

This work provides valuable information about unexplored catalytic systems tested in the transesterification reaction of vegetable oil with methanol. It was demonstrated that natural zeolite treatment leads to enhanced catalytic activity and yield of biodiesel production. The activation of the catalytic material in a mixture of 5% H₂–95% Ar resulted in an improvement of the values of the TG conversion and fatty acid methyl esters (FAME) yield. In addition, it was proven that the incorporation of CaO, MgO and SrO oxides onto the natural zeolite surface improves the TG conversion and FAME yield values in the transesterification reaction.     

Coordination properties of N,N′-bis(5-methylsalicylidene)-2-hydroxy-1,3-propanediamine with d- and f-electron ions: crystal structure,stability in solution,spectroscopic and spectroelectrochemical studies

Template reaction between 5-methylsalicylaldehyde and 2-hydroxy-1,3-propanediamine in the presence of copper ion led to dinuclear and mononuclear copper(ii) complexes [Cu₂L(CH₃COO)(CH₃OH)](CH₃OH) (1) and [CuHL](CH₃OH) (2), where H₃L is N,N′-bis(5-methylsalicylidene)-2-hydroxy-1,3-propanediamine. The result of the reactions between 5-methylsalicylaldehyde and 2-hydroxy-1,3-propanediamine in the presence of lanthanide ions and/or copper(ii) ion was N,N′-bis(5-methylsalicylidene)-2-hydroxy-1,3-propanediamine (H₃L B) or [CuHL](CH₃OH) (2), respectively. Structures of the compounds were determined by single-crystal X-ray diffraction and physicochemical methods. The microstructures and phase compositions of crystals were studied by scanning electron microscopy (SEM). In dinuclear complex [Cu₂L(CH₃COO)(CH₃OH)](CH₃OH) (1), two copper(ii) ions are bond to one H₃L ligand and one acetate ion. Coordination modes of the two copper centers are different: the geometry of copper 1 is almost ideal square-planar, while that for copper 2 can be described as tetragonal pyramidal. In complex [CuHL](CH₃OH) (2), the copper(ii) ion is four coordinated and the coordination, rather than square-planar, can be described as flattened tetrahedral. Formation of complexes between copper(ii) or lanthanide ions with N,N′-bis(5-methylsalicylidene)-2-hydroxy-1,3-propanediamine (H₃L) was also studied in solution by pH potentiometry. It should be mentioned that the complexes of lanthanide ions exist only in solution. Additionally, the salen-type ligand H₃L and its dinuclear and mononuclear copper(ii) complexes were studied by cyclic voltammetry, and their spectroelectrochemical properties were examined.

The self-assembled metal-promoted synthesis and properties of N,N′-bis(5-methylsalicylidene)-2-hydroxy-1,3-propanediamine (H₃L) complexes with d- and f-metal ions are described.     

Invasive mycoses in children receiving hemopoietic SCT

Invasive mycoses represent a rare but severe complication following hemopoietic SCT (HSCT) in children. Their incidence is related to the type of donor, being higher after allogeneic transplant, especially from alternative donors. Moreover, the incidence of invasive mycoses varies in the different post transplant phases. Neutropenia, lymphopenia, GvHD, high-dose steroids or other immunosuppressive drugs represent well-known risk factors. The clinical features of invasive mycoses after HSCT in children are similar to those observed in adults, and the diagnostic tools, including Aspergillus galactomannan antigen detection, are feasible also in pediatrics. Mortality due to invasive mycoses after HSCT in children is high.     

Double-strand breaks associated with repetitive DNA can reshape the genome

Ionizing radiation is an established source of chromosome aberrations (CAs). Although double-strand breaks (DSBs) are implicated in radiation-induced and other CAs, the underlying mechanisms are poorly understood. Here, we show that, although the vast majority of randomly induced DSBs in G₂ diploid yeast cells are repaired efficiently through homologous recombination (HR) between sister chromatids or homologous chromosomes, ≈2% of all DSBs give rise to CAs. Complete molecular analysis of the genome revealed that nearly all of the CAs resulted from HR between nonallelic repetitive elements, primarily Ty retrotransposons. Nonhomologous end-joining (NHEJ) accounted for few, if any, of the CAs. We conclude that only those DSBs that fall at the 3–5% of the genome composed of repetitive DNA elements are efficient at generating rearrangements with dispersed small repeats across the genome, whereas DSBs in unique sequences are confined to recombinational repair between the large regions of homology contained in sister chromatids or homologous chromosomes. Because repeat-associated DSBs can efficiently lead to CAs and reshape the genome, they could be a rich source of evolutionary change.     

Status of minimal residual disease after induction predicts outcome in both standard and high-risk Ph-negative adult acute lymphoblastic leukaemia. The Polish Adult Leukemia Group ALL 4-2002 MRD Study

The treatment of adults with Philadelphia-negative acute lymphoblastic leukaemia (ALL) depends on the presence of risk factors including age, white blood cell count, immunophenotype and time to complete remission. In recent years, status of minimal residual disease (MRD) has been postulated as an additional risk criterion. This study prospectively evaluated the significance of MRD. Patients were treated with a uniform Polish Adult Leukemia Group (PALG) 4-2002 protocol. MRD status was assessed after induction and consolidation by multiparametric flow cytometry. Out of 132 patients included (age, 17–60 years), 116 patients were suitable for analysis. MRD level ≥0·1% of bone marrow cells after induction was found to be a strong and independent predictor for relapse in the whole study population ( P  < 0·0001), as well as in the standard risk (SR, P  = 0·0003) and high-risk ( P  = 0·008) groups. The impact of MRD after consolidation on outcome was not significant. The combination of MRD status with conventional risk stratification system identified a subgroup of patients allocated to the SR group with MRD <0·1% after induction who had a very low risk of relapse of 9% at 3 years as opposed to 71% in the remaining subjects ( P  = 0·001). We conclude that MRD evaluation after induction should be considered with conventional risk criteria for treatment decisions in adult ALL.     

Optimization and regeneration kinetics of lymphatic-specific photodynamic therapy in the mouse dermis

Lymphatic vessels transport fluid, antigens, and immune cells to the lymph nodes to orchestrate adaptive immunity and maintain peripheral tolerance. Lymphangiogenesis has been associated with inflammation, cancer metastasis, autoimmunity, tolerance and transplant rejection, and thus, targeted lymphatic ablation is a potential therapeutic strategy for treating or preventing such events. Here we define conditions that lead to specific and local closure of the lymphatic vasculature using photodynamic therapy (PDT). Lymphatic-specific PDT was performed by irradiation of the photosensitizer verteporfin that effectively accumulates within collecting lymphatic vessels after local intradermal injection. We found that anti-lymphatic PDT induced necrosis of endothelial cells and pericytes, which preceded the functional occlusion of lymphatic collectors. This was specific to lymphatic vessels at low verteporfin dose, while higher doses also affected local blood vessels. In contrast, light dose (fluence) did not affect blood vessel perfusion, but did affect regeneration time of occluded lymphatic vessels. Lymphatic vessels eventually regenerated by recanalization of blocked collectors, with a characteristic hyperplasia of peri-lymphatic smooth muscle cells. The restoration of lymphatic function occurred with minimal remodeling of non-lymphatic tissue. Thus, anti-lymphatic PDT allows control of lymphatic ablation and regeneration by alteration of light fluence and photosensitizer dose.     

Value of short exercise and short exercise with cooling tests in the diagnosis of myotonic dystrophies (DM1 AND DM2)

Introduction: Standard electromyography (EMG) is useful in the diagnosis of myotonic dystrophy type 1 (DM1) and type 2 (DM2), but it does not differentiate between them. The aim of this study was to estimate the utility of the short exercise test (SET) and short exercise test with cooling (SETC) in differentiating between DM1 and DM2. Methods: SET and SETC were performed in 32 patients with DM1 (mean age 35.8 ± 12.7 years) and 28 patients with DM2 (mean age 44.5 ± 12.5 years). Results: We observed a significant decline in compound motor action potential (CMAP) amplitude in DM1 with both SET and SETC immediately after effort. In DM2, there was no marked change in CMAP amplitude with either SET or SETC. Conclusions: SET and SETC may serve as useful tools for clinical differentiation between DM1 and DM2, and they may be used as a guide for molecular testing. Muscle Nerve 49 : 277–283, 2014