Photodynamic therapy

This article describes the term of photodynamic therapy, a relatively new way of cancer treatment and gives the rewiev of the commonly used photosensitizers, expecially the phthalocyanines and their way of action. The last part is devoted to the action of PDT on human erythrocytes.Zadanie pt. „Digitalizacja i udostępnienie w Cyfrowym Repozytorium Uniwersytetu Łódzkiego kolekcji czasopism naukowych wydawanych przez Uniwersytet Łódzki” nr 885/P-DUN/2014 dofinansowane zostało ze środków MNiSW w ramach działalności upowszechniającej naukę

Influence of MLS laser radiation on erythrocyte membrane fluidity and secondary structure of human serum albumin

The biostimulating activity of low level laser radiation of various wavelengths and energy doses is widely documented in the literature, but the mechanisms of the intracellular reactions involved are not precisely known. The aim of this paper is to evaluate the influence of low level laser radiation from an multiwave locked system (MLS) of two wavelengths (wavelength = 808 nm in continuous emission and 905 nm in pulsed emission) on the human erythrocyte membrane and on the secondary structure of human serum albumin (HSA). Human erythrocytes membranes and HSA were irradiated with laser light of low intensity with surface energy density ranging from 0.46 to 4.9 J cm(−2) and surface energy power density 195 mW cm(−2) (1,000 Hz) and 230 mW cm(−2) (2,000 Hz). Structural and functional changes in the erythrocyte membrane were characterized by its fluidity, while changes in the protein were monitored by its secondary structure. Dose-dependent changes in erythrocyte membrane fluidity were induced by near-infrared laser radiation. Slight changes in the secondary structure of HSA were also noted. MLS laser radiation influences the structure and function of the human erythrocyte membrane resulting in a change in fluidity

Hemolytic uremic syndrome in a patient with acute pancreatitis

A 40-year-old female patient with no previous medical history was admitted to the Department of Surgery due to symptoms of acute pancreatitis (AP). On the 3rd day of her hospitalization, significant anemia with thrombocytopenia and signs of acute kidney injury with oliguria were observed. In the course of differential diagnosis, after excluding sepsis and bleeding, based on the presence of hemolysis parameters (schistocytes in blood, low haptoglobin concentration, and high lactate dehydrogenase concentration), hemolytic uremic syndrome (HUS) was diagnosed. Treatment with plasmapheresis and steroids was implemented, resulting in inhibition of hemolysis, normalization of the number of platelets, and improvement of renal function. Given the lack of E. coli enterotoxin and Shiga toxin in the feces, STEC HUS was excluded, and the regular ADAMS-13 activity excluded atypical HUS. The entire clinical picture, including an excellent response to the treatment, allowed for the diagnosis of HUS as a complication of acute pancreatitis

The diagnostic role of 68Ga-DOTATATE PET/CT in the detection of neuroendocrine tumours

BACKGROUND: Positron emission tomography (PET) combined with computer tomography (CT) using 68Ga-DOTATATE is a promising method for the evaluation of patients with recognised or suspected neuroendocrine tumours (NET). The aim of this study was to assess the diagnostic value of 68Ga-DOTATATE PET/CT in the visualisation of the expression of somatostatin receptors (SSTR) and identification of new lesions. MATERIAL AND METHODS: Between December 2009 and January 2011 ninety-seven patients with confirmed (88 cases) or suspected (9 cases) NET underwent 68Ga DOTATATE PET/CT. The primary, confirmed or suspected, NET localizations were: GEP tumours — 71 patients; medullary thyroid carcinoma — 4 patients; cancer of an unknown primary — 14 patients; and NET in other localisations — 8 patients. PET/CT acquisitions were performed using standard techniques, 45 to 60 minutes after the intravenous injection of 111–185 MBq 68Ga-DOTATATE. RESULTS: 68Ga-DOTATATE PET/CT detected the presence of lesions demonstrating the somatostatin receptor affinity in 50 of the 97 patients (51.5%) and was negative in 47 patients (48.5%). Among 14 patients with metastatic unknown primary cancer, in 5 patients (45.5%) the primary tumour site was identified, and in 4 patients with medullary thyroid cancer distant metastases with SSTR expression were localized in only one patient. CONCLUSIONS: Our findings confirm the diagnostic role of 68Ga-DOTATATE PET/CT as an accurate method of identifying primary tumours and distant metastases. It provides information on tumour cell receptors status, which has a significant bearing on planning target radionuclide therapy. Overall, 68Ga-DOTATATE PET/CT can be used in staging, re-staging, and in regular follow up of oncology patients. Nuclear Med Rev 2011; 14, 1: 16–2

Poly(propylene imine) dendrimers and amoxicillin as dual-action antibacterial agents

Besides acting as antimicrobial compounds, dendrimers can be considered as agents that improve the therapeutic effectiveness of existing antibiotics. In this work we present a new approach to using amoxicillin (AMX) against reference strains of common Gram-negative pathogens, alone and in combination with poly(propylene imine) (PPI) dendrimers, or derivatives thereof, in which 100% of the available hydrogen atoms are substituted with maltose (PPI 100%malG3). The concentrations of dendrimers used remained in the range non-toxic to eukaryotic cells. The results indicate that PPI dendrimers significantly enhance the antibacterial effect of amoxicillin alone, allowing antibiotic doses to be reduced. It is important to reduce doses of amoxicillin because its widespread use in medicine could lead to the development of bacterial resistance and environmental pollution. This is the first report on the combined antibacterial activity of PPI surface-modified maltose dendrimers and amoxicillin

Binding properties of polyamidoamine dendrimers

ABSTRACT: Dendrimers are globular, hyperbranched polymers possessing a high concentration of surface functional groups and internal cavities. These unique features make them good host molecules for small ligands. To reveal relationships between dendrimer size and its encapsulating properties, the interactions of the fourth and the sixth generations of polyamidoamine dendrimers (PAMAM G4 and PAMAM G6) with a fluorescent dye 1-anilinonaphthalene-8-sulfonate (ANS) were studied. Because ANS is a fluorescent molecule and its fluorescence is very sensitive to changes in its microenvironment, it was possible to use spectrofluorometric methods to evaluate the interactions with dendrimers. A double fluorometric titration method was used to estimate a binding constant and the number of binding centers. There were two types of dendrimer binding centers characterized by different affinity towards ANS. For PAMAM G4, the values of K b and n for low-affinity and high-affinity sites equaled to 2.6 Â 10 5 , 0.60 and 3.70 Â 10 6 , 0.34, respectively, whereas in the case of PAMAM G6, these values equaled to 1.2 Â 10 5 , 76.34 and 1.38 Â 10 6 , 22.73. It was observed that the size of the dendrimer had a strong impact on the number of ANS molecules that interacted with dendrimers and their location within the macromolecule

Influence of valoneoyl groups on the interactions between Euphorbia tannins and human serum albumin

Abstract Tannins belonging to plant polyphenols, are large group of compounds with diverse biological activity. Many of them are being studied as potential natural medicine due to their antioxidant, antiviral, antibacterial or anticancer properties. However, so far little is known about the structural and functional relations in protein-tannin interactions, in particularly the role of valoneoyl groups in tannin structure. In this study we first investigated the mechanisms of interaction 1,2-di-O-galloyl-4,6-valoneoyl-β-D-glucose (Tannin 1), 2-O-galloyl-4,6-valoneoyl-β-D-glucose (Tannin 2), 3-O-galloyl-1,2-valoneoyl-β-D-glucose (Tannin 3) isolated from Euphorbia plants with human serum albumin (HSA). To get more detailed information about nature of albumin-tannin interactions besides standard Trp fluorescence quenching analysis we used also transmission electron microscopy (TEM), circular dichroism (CD) and fluorescence labelling (ANS dye) techniques. It was shown that all the tannins strongly interacted with HSA and quenched the tryptophan amino acid (Trp) fluorescence but slightly changed protein secondary structure (circular dichroism CD analysis). TEM demonstrated that all used compounds formed complexes with HSA. Tannin 3 most strongly quenched HSA fluorescence and changed protein dynamic as well as had the highest binding constant (12.4 ± 1.1 × 1013 M−1 s−1 in comparison with 7.0 ± 0.38 × 1013 M−1 s−1 for tannin 1 and 8.6 ± 1.1 × 1013 M−1 s−1 for tannin 2). For tannin 1 that was the largest of the studied compounds was observed the weakest influence on the fluorescence parameters, probably due to the effect of steric hindrancelimiting interaction with albumin Trp pocket. On the other hand T1 induced the strongest changed secondary structure of HSA in comparison to another studied tannins. Our results demonstrated that all used tannins interact with albumin by complex formation but in the manner depends on chemical structure and flexibility of studied compounds

Affecting NF-κB cell signaling pathway in chronic lymphocytic leukemia by dendrimers-based nanoparticles

Abstract The complex genetic diversity of chronic lymphocytic leukemia (CLL) makes it difficult to determine the effective and durable therapy beneficial to patients. During the several past years' significant insights in the biology of the disease and its treatment have been made, allowing for the identification of promising novel therapeutic agents. The investigation of signaling pathways to understand the biological character of CLL together with the development of molecular profiling is key in personalized approach in therapy for this disease. As it was already proven, maltotriose (M3) modified fourth generation poly(propylene imine) dendrimers(PPI-G4) modulate BCR, TRAIL and WNT signaling pathway gene expression in CLL cells and strongly influence their survival by inducing apoptosis and inhibiting proliferation. The aim of this study was to evaluate the influence of PPI-G4-M3 dendrimers on NFκB pathway gene expression in CLL (MEC-1) cells with 60 K microarray, as it is one of the major factors in the pathogenesis of B-cell neoplasms. The findings were compared with those obtained with Fludarabine (FA) and the results indicate that PPI-G4-M3 dendrimers affect the expression of the examined genes and exert comparable effect on the CLL cells to FA. Dendrimers are one of the most potent groups of nanometer-sized macromoleculesfor closing the gap between the present ineffective treatment and the future effective personalized therapy due to their potential versatile biological propertie

Ruthenium metallodendrimer against triple-negative breast cancer in mice

Carbosilane metallodendrimers, based on the arene Ru(II) complex (CRD13) and integrated to imino-pyridine surface groups have been investigated as an anticancer agent in a mouse model with triple-negative breast cancer. The dendrimer entered into the cells efficiently, and exhibited selective toxicity for 4T1 cells. In vivo investigations proved that a local injection of CRD13 caused a reduction of tumour mass and was non-toxic. ICP analyses indicated that Ru(II) accumulated in all tested tissues with a greater content detected in the tumour.European CommissionMinisterio de Economía y CompetitividadComunidad de MadridJunta de Comunidades de Castilla-La Manch