Objectives  The aim of this study was to investigate the interaction of the anticancer drug mitoxantrone with non-ionic micelles, as simple model systems of biological membranes. Methods  UV-VIS absorption spectroscopy was used to quantify the drug-surfactant micelle interactions in terms of the binding constant and the micelle-water partition coefficient of the drug. Key findings  Interaction of mitoxantrone with non-ionic micelles reduces the dimerization process of mitoxantrone, the drug molecules being encapsulated into micelles as monomer. The strength of the interaction between mitoxantrone and non-ionic micelles is higher at pH 10 than at pH 7.4, and depends on the surfactant in the order Tween 80 > Tween 20 > Triton X-100. The higher partition coefficient at pH 10 compared to pH 7.4 suggests that at basic pH the deprotonated mitoxantrone is incorporated more efficiently into the hydrophobic medium of non-ionic micelles compared to physiological pH, when the protonated drug is predominant. Conclusions  These results on simple model systems miming the drug-membrane interactions contribute to the elucidation of the behaviour of the drug in vivo, as well as the possible utilization of surfactant micelles as drug carriers.

The study focuses on the possible influences of intra (I) lobular (L) stromal compounds [intertubular spaces and seminiferous (S) tubule (T) wall (W)] morphologic changes on S epithelium (E) during ageing process. The material consisted of surgical samples of testicular tissue from 192 patients with orchidectomy for prostate carcinoma. Seven age groups were designed, from 50 to 80 years. Tissue samples were fixed in neutral buffered formalin, embedded in paraffin stained with HE, Goldner and Gömöri and immunomarked (in a subgroup of 28 cases) for smooth muscle actin, collagen IV, and CD34. SE had an uneven involution, both individually and inter-individually, but with normal spermatogenesis in many of ST. E degenerative changes were seen mainly in L periphery. Different stages of maturation arresting were more frequent in older patients. IL septae had changes with extremely variable intensity, dispersed mainly in L periphery, without significant spread and without extensive trend with ageing. Leydig cells showed focal hyperplasia without extensive trend related with ageing. STW presented strictly in the internal layer of lamina propria (apposed to basement membrane of ES) a focal sclerosis, with variable extension concerning its presence, thickness and T circumference (T without sclerosis, with focal sclerosis and with fibro-hyaline "collar"- FHyC) but not related with ageing. IL arteriolae showed focal areas of degeneration with a wide individual and inter-individual range of intensity and extension, but not related with age. Capillary network (CN), with both its peri-T and intramural segments, was present in all age groups, with no quantitative endothelial changes and decreasing only in very old cases. FHyC was often associated with E atrophy. STW focal sclerosis could explain focal degeneration of SE in senescence, although CN undergoes no significant changes.

Bladder cancer (BC) is the most common tumor of the urinary tract. White light cystoscopy (WLC) is currently considered the standard investigation for diagnosis of bladder tumors. Recent studies suggest that using exogenous fluorescence (photodynamic diagnosis, PDD) can improve its diagnostic sensitivity and specificity. Our study aims to analyze the value of using fluorescent cystoscopy (PDD) in the diagnosis and treatment of non-muscle invasive bladder cancer (NMIBC). The study designed as a prospective randomized clinical trial was conducted over a 12 months period and included 44 patients with primitive NMIBC diagnosed and treated in our department in 2009. Twenty-two patients were included in the study group (PDD), while 22 patients were diagnosed and treated by conventional methods (WLC). There were no statistically significant differences between the two groups regarding age, sex, place of origin, smoking history, clinical symptoms or presence of urological history as well as tumor size, location or number. Fluorescence cystoscopy examination identified 25.8% more tumors than the conventional examination (p=0.004). We demonstrated a significant reduction of tumor recurrence rates at 3, 6, 9 and 12 months by using PDD (HR=0.3271, 95% CI 0.1091-0.9809; p=0.0461). The use of PDD in patients with NMIBC results in significant improvement of the efficiency of their initial diagnosis cystoscopy (by over 25%). We demonstrated improved patient prognosis and quality of life following conservative TUR treatment of these tumors by significantly reducing the tumor recurrence rate (by 9-27%) in the first year of follow-up.

Synchronous development of a second primary cancer in patients with esophageal squamous cell carcinoma was reported in 2.73%-11% of the cases. Although the synchronous association between esophageal and renal cancer is very rare, an increasingly number of cases is reported in medical literature. This study's aim is to report a case of synchronous esophageal squamous cell carcinoma and an urothelial carcinoma of the right kidney. Patient G.D. was admitted in our clinic with esophageal cancer diagnosis; during the preoperative work-up protocol, an asymptomatic right renal mass was discovered. A nephroureteroscopy with biopsy was performed and the urothelial renal cancer diagnosis was established. The patient is proposed for seriate surgery: nephroureterectomy on the first stage, then esophagectomy with gastric reconstruction was performed. Postoperative evolution was unfavourable, patient being finally discharged, on his request, with severely altered status.

The interaction of anticancer drug mitoxantrone with cationic surfactant cetyltrimethylammonium bromide (CTAB) has been investigated by absorption spectroscopy as a function of surfactant concentration ranging from the premicellar to postmicellar region at pH 7.4 and 10. Interaction of mitoxantrone with CTAB micelles induces a bathochromic shift of both absorption maxima and spectral data showed that the micellization reduces the dimerization process and mitoxantrone is bound into micelles in the monomeric form. Binding constant and partition coefficient were estimated using the red shifts of the absorption maxima in the presence of surfactant. From the resulting binding constants for mitoxantrone-surfactant interactions, it was concluded that the hydrophobic interactions have a great effect on the binding of mitoxantrone to CTAB micelles. Also, by comparing the partition coefficients obtained using pseudo-phase model, the hydrophobic interactions have a major role in the distribution of mitoxantrone between micelle-water phases. Gibbs free energy of binding and distribution of mitoxantrone between the bulk aqueous medium and surfactant micelles were calculated.

A novel approach of identifying metal atoms within a metal-organic surface coordination network using scanning tunnelling microscopy (STM) is presented. The Cu adatoms coordinated in the porous surface network of 1,3,8,10-tetraazaperopyrene (TAPP) molecules on a Cu(111) surface give rise to a characteristic electronic resonance in STM experiments. Using density functional theory calculations, we provide strong evidence that this resonance is a fingerprint of the interaction between the molecules and the Cu adatoms. We also show that the bonding of the Cu adatoms to the organic exodentate ligands is characterised by both the mixing of the nitrogen lone-pair orbitals of TAPP with states on the Cu adatoms and the partial filling of the lowest unoccupied molecular orbital (LUMO) of the TAPP molecule. Furthermore, the key interactions determining the surface unit cell of the network are discussed.

In-vitro evaluation of the interaction of anticancer drug mitoxantrone with anionic surfactant sodium dodecyl sulfate (SDS), was performed in physiological conditions (phosphate buffer, pH 7.4) by spectral (UV-Vis absorption) and electrochemical (cyclic and linear voltammetry) methods. The stoichiometry of interaction, the binding constants and diffusion coefficients of free and bound drug were determined. The partition coefficient of mitoxantrone between aqueous phase and SDS micelles was calculated, and the results indicated that it is strongly dependent on the drug concentration. Both absorption and cyclic voltammetry results have outlined two distinct processes depending on the surfactant concentration: process I in premicellar range, assigned to the interaction of the drug with the surfactant molecules, when electrostatic forces play an important role in the formation of the mitoxantrone-SDS complex with a defined stoichiometry; and process II in micellar range, when the surfactant micelles are formed and the drug is encapsulated in micelles in monomer form. The spectral results have indicated that the drug is most probably located in the micelle surface layer, both electrostatic and polar interactions playing important role in the binding of drug to SDS micelles. Possible application of this system as a micellar drug-carrier was also considered.

RATIONALE: In rats, prenatal restraint stress (PRS) induces persistent behavioral and neurobiological alterations leading to a greater consumption of psychostimulants during adulthood. However, little is known about alcohol vulnerability in this animal model. OBJECTIVES: We examined in adolescent and adult male Sprague Dawley rats the long-lasting impact of PRS exposure on alcohol consumption. METHODS: PRS rats were subjected to a prenatal stress (three daily 45-min sessions of restraint stress to the mothers during the last 10 days of pregnancy). Alcohol preference was assessed in a two-bottle choice paradigm (alcohol 2.5%, 5%, or 10% versus water), in both naïve adolescent rats and adult rats previously exposed to a chronic alcohol treatment. Behavioral indices associated with incentive motivation for alcohol were investigated. Finally, plasma levels of transaminases (marker of hepatic damages) and DeltaFosB levels in the nucleus accumbens (a potential molecular switch for addiction) were evaluated following the chronic alcohol exposure. RESULTS: Alcohol preference was not affected by PRS. Contrary to our expectations, stressed and unstressed rats did not display signs of compulsive alcohol consumption. The consequences of the alcohol exposure on locomotor reactivity and on transaminase levels were more prominent in PRS group. Similarly, PRS potentiated alcohol-induced DeltaFosB levels in the nucleus accumbens. CONCLUSION: Our data suggest that negative events occurring in utero do not modulate alcohol preference in male rats but potentiate chronic alcohol-induced molecular neuroadaptation in the brain reward circuitry. Further studies are needed to determine whether the exacerbated DeltaFosB upregulation in PRS rats could be extended to other reinforcing stimuli.

The structural chemistry and reactivity of 1,3,8,10-tetraazaperopyrene (TAPP) on Cu(111) under ultra-high-vacuum (UHV) conditions has been studied by a combination of experimental techniques (scanning tunneling microscopy (STM) and X-ray photoelectron spectroscopy, XPS) and DFT calculations. Depending on the deposition conditions, TAPP forms three main assemblies, which result from initial submonolayer coverages based on different intermolecular interactions: a close-packed assembly similar to a projection of the bulk structure of TAPP, in which the molecules interact mainly through van der Waals (vDW) forces and weak hydrogen bonds; a porous copper surface coordination network; and covalently linked molecular chains. The Cu substrate is of crucial importance in determining the structures of the aggregates and available reaction channels on the surface, both in the formation of the porous network for which it provides the Cu atoms for surface metal coordination and in the covalent coupling of the TAPP molecules at elevated temperature. Apart from their role in the kinetics of surface transformations, the available metal adatoms may also profoundly influence the thermodynamics of transformations by coordination to the reaction product, as shown in this work for the case of the Cu-decorated covalent poly(TAPP--Cu) chains.

The self-assembly properties of two Zn(II) porphyrin isomers on Cu(111) are studied at different coverage by means of scanning tunneling microscopy (STM). Both isomers are substituted in their meso-positions by two voluminous 3,5-di(tert-butyl)phenyl and two rod-like 4'-cyanobiphenyl groups, respectively. In the trans-isomer, the two 4'-cyanobiphenyl groups are opposite to each other, whereas they are located at right angle in the cis-isomer. For coverage up to one monolayer, the cis-substituted porphyrins self-assemble to form oligomeric macrocycles held together by antiparallel CNCN dipolar interactions and CNH-C(sp(2)) hydrogen bonding. Cyclic trimers and tetramers occur most frequently but everything from cyclic dimers to hexamers can be observed. Upon annealing of the samples at temperatures >150 degrees C, dimeric macrocyclic structures are observed, in which the two porphyrins are bridged by Cu atoms, originating from the surface, under formation of two CNCuNC coordination bonds. The trans-isomer builds up linear chains on Cu(111) at low coverage, whereas for higher coverage the molecules assemble in a periodic, densely packed structure. Both cis- and trans-bis(4'-cyanobiphenyl)-substituted Zn(II) porphyrins behave very differently on Cu(111) compared to similar porphyrins in literature on less reactive surfaces such as Au(111) and Ag(111). On the latter surfaces, there is no signal visible between molecular orientation and the crystal directions of the substrate, whereas on Cu(111), very strong adsorbate-substrate interactions have a dominating influence on all observed structures. This strong porphyrin-substrate interaction enables a much broader variety of structures, including also less favorable intermolecular bonding motifs and geometries.