A photoinduced pH jump applied to drug release from cucurbit[7]uril

A proof-of-principle for the application of a photoinduced pH jump for delivery of the Hoechst 33258 drug by disassembly of its host-guest complex with cucurbit[7]uril is described

YKL-40 IN SERA OF BREAST TUMOR PATIENTS

YKL-40, also known as human cartilage glycoprotein 39, is a member of the “mammalian chitinase-like proteins”, but lacking of chitinase activity. Increased variations in serum concentrations are associated with inflammatory processes and several types of cancer.In this study we evaluated serum YKL-40 levels in healthy controls and in women with benign and malignant breast tumors. YKL-40 serum levels were measured by enzyme-linked immunosorbent assay – ELISA in 32 patients. The effect of the various factors was analyzed using correlation and regression analyses simultaneously determining the size and direction of correlation. The level of statistical significance of null hypothesis was P<0.05. Our study showed that serum YKL-40 level in breast carcinoma was significantly higher than the concentration in healthy controls (p<0.01). The changes in protein levels were higher than 25%. Serum YKL-40 increased with age (rxy=0.46). The correlation between glycoprotein quantity and age was positive, but feeble.This investigation is first in Bulgaria to demonstrate significantly elevated serum YKL-40 level in breast carcinoma compared to women with benign breast tumors and healthy controls. Longitudinal studies are needed to confirm YKL-40 as a potential and reliable biomarker

Ethological Model for Diagnosis of Infectious Encephalomyelitis in Broiler Chickens

The purpose of the study was to establish the specific symptomatic ethological pathognomonic complex of infectious encephalomyelitis in poultry. The behavioural changes were monitored in 2-week-old broiler chickens  (total number 10,500 housed in three premises). The typical pathoethological manifestations of infectious encephalomyelitis were investigated in broiler chickens through six behavioural activities – locomotion, appetite, water drinking, pareses, paralyses, posture. As a result of the survey, the specific ethological pathognomonic complex for infectious encephalomyelitis in chickens was identified. These clinical manifestations of a pathoethological complex and specific behavioural activities could be used to support the diagnosis

Release of High-Energy Water as an Essential Driving Force for the High-Affinity Binding of Cucurbit[<i>n</i>]urils

Molecular dynamics simulations and isothermal titration calorimetry (ITC) experiments with neutral guests illustrate that the release of high-energy water from the cavity of cucurbit­[<i>n</i>]­uril (CB<i>n</i>) macrocycles is a major determinant for guest binding in aqueous solutions. The energy of the individual encapsulated water molecules decreases with increasing cavity size, because larger cavities allow for the formation of more stable H-bonded networks. Conversely, the total energy of internal water increases with the cavity size because the absolute number of water molecules increases. For CB7, which has emerged as an ultrahigh affinity binder, these counteracting effects result in a maximum energy gain through a complete removal of water molecules from the cavity. A new design criterion for aqueous synthetic receptors has therefore emerged, which is the optimization of the size of cavities and binding pockets with respect to the energy and number of residing water molecules

Inclusion of neutral guests by water-soluble macrocyclic hosts – a comparative thermodynamic investigation with cyclodextrins, calixarenes and cucurbiturils

<p>The driving forces of association between three different families of macrocycles as hosts, namely cyclodextrins (<i>α</i>-, <i>β</i>-, and <i>γ</i>-), <i>p</i>-sulfonatocalix[<i>n</i>]arenes (<i>n</i> = 4–6) as well as cucurbit[<i>n</i>]urils (<i>n</i> = 6–8), and three different bicyclic azoalkane homologues as guests, namely 2,3-diazabicyclo[2.2.1]hept-2-ene (DBH), 2,3-diazabicyclo[2.2.2]oct-2-ene (DBO) as well as 2,3-diazabicyclo[2.2.3]non-2-ene (DBN), were examined by means of calorimetric titrations, NMR spectroscopy and molecular dynamics simulation, all in aqueous solution. The small, spherical and uncharged guests preferably bind inside the cavities of the medium sized hosts. The inclusion complexation by <i>β</i>-cyclodextrin and <i>p</i>-sulfonatocalix[4]arene shows medium binding affinities (millimolar), while cucurbit[7]uril macrocycle shows very strong binding (micromolar). For all types of macrocycles, the complex formation is enthalpically driven (Δ<i>H</i>° < 0), accompanied by slightly unfavourable entropy changes (Δ<i>S</i>° < 0). The results are discussed in terms of the flexibility of the hosts, the hydrophobic character of their cavities and the release of high-energy water upon binding, and generalised by including two additional guests, the ketones cyclopentanone and (+)-camphor.</p

YKL-40 – A NEW DIAGNOSTIC BIOMARCER FOR BENIGN BREAST DISEASES AND BREAST CANCER

Benign breast diseases encompass a wide spectrum of lesions, which raise a lot of questions about their classification, diagnosis, prognosis and surgical treatment. The aim of this study is to measure the serum level of YKL-40 in cases of different groups of benign breast diseases, to compare it to the level of healthy women as well as to those with breast cancer and to examine its tissue expression after surgical treatment. We use it as a diagnostic marker and as a criterion for differential diagnosis.Forty nine (49) patients with benign breast diseases and twenty (20) patients with breast cancer were examined. All of them had their serum level of YKL-40 measured preoperatively and its tissue expression examined immunohystochemically after the surgical intervention. There were significant differences in both concentration and tissue expression of this marker in patients with different groups of benign breast diseases and breast cancer. YKL-40 can be an important biomarker in the diagnosis and differential diagnosis of breast diseases