Cholesteryl butyrate solid lipid nanoparticles inhibit the adhesion and migration of colon cancer cells.

BACKGROUND AND PURPOSE Cholesteryl butyrate solid lipid nanoparticles (cholbut SLN) provide a delivery system for the anti-cancer drug butyrate. These SLN inhibit the adhesion of polymorphonuclear cells to the endothelium and may act as anti-inflammatory agents. As cancer cell adhesion to endothelium is crucial for metastasis dissemination, here we have evaluated the effect of cholbut SLN on adhesion and migration of cancer cells. EXPERIMENTAL APPROACH Cholbut SLN was incubated with a number of cancer cell lines or human umbilical vein endothelial cells (HUVEC) and adhesion was quantified by a computerized micro-imaging system. Migration was detected by the scratch 'wound-healing' assay and the Boyden chamber invasion assay. Expression of ERK and p38 MAPK was analysed by Western blot. Expression of the mRNA for E-cadherin and claudin-1 was measured by RT-PCR. KEY RESULTS Cholbut SLN inhibited HUVEC adhesiveness to cancer cell lines derived from human colon-rectum, breast, prostate cancers and melanoma. The effect was concentration and time-dependent and exerted on both cancer cells and HUVEC. Moreover, these SLN inhibited migration of cancer cells and substantially down-modulated ERK and p38 phosphorylation. The anti-adhesive effect was additive to that induced by the triggering of B7h, which is another stimulus inhibiting both ERK and p38 phosphorylation, and cell adhesiveness. Furthermore, cholbut SLN induced E-cadherin and inhibited claudin-1 expression in HUVEC. CONCLUSION AND IMPLICATIONS These results suggest that cholbut SLN could act as an anti-metastastic agent and they add a new mechanism to the anti-tumour activity of this multifaceted preparation of butyrate.

Computerized detection of clustered microcalcifications: a modular approach with non-linear filters.

The ideal computerized mammogram processing system still needs to be developed. In order to achieve maximum flexibility we suggest a modular scheme, dividing the processing sequence into functionally autonomous modules. This paper provides a general scheme for detection and/or automated recognition of microcalcifications. Some modules that perform ROI selection are introduced, using special non-linear filters designed for microcalcification detection. A first type of filter selects pixels with specific statistical local features, as compared to the local mean. Among these, only pixels satisfying particular constraints on the local standard deviation are kept. Another type of filter then checks the local mean values of gradient components, so that sharp variations, unrelated to small close objects, can be eliminated. The scheme thus applies different non-linear filters in combination, making precise identification of clustered microcalcifications possible. This modular approach seems greatly to simplify system maintenance and consistency, as well as affording a comparison of different processing techniques and parameters.

Mechanical effects of heart pulse propagation on a vessel-graft suture line stress.

The effects of vessel joint where the both sides have different wall properties on the heart pulse propagation are investigated. Such a local disturbance can influence post-transplantation pathology and evolution of the organ inconsistency. Using a mathematical model, developed in a previous article, we perform analytical analysis and present some qualitative and quantitative estimations. The effects of jointed vessels with different thicknesses and radii on the local concentration of the pressure, radial wall displacement, bending moment and shear force are analyzed in detail. In particular, it is obtained that the bending and shear stresses at a joint sharply and strongly increase in comparison with the uniform vessel ones.

A simple model of blood flow rate reduction in haemodynamic disorders of the spleen.

The structural rearrangement of human sheathed capillaries in congestive splenomegaly has been considered. In abnormal spleens the external diameter and wall thickness were decreased, while the internal diameter was increased. Moreover, the total length and the absolute number of sheathed capillaries were increased, though not as much as the whole red pulp volume. Thus, in congestive splenomegaly, in addition to the well-known changes of the sinuses, the terminal arterial passages also appear to participate in the morphological rearrangement of the red pulp. The purpose of this paper is to formulate a simple dynamic model explaining the reduction of blood flow rate in the pathologically modified spleen. The main advantage of the present approach is that the coefficients inserted in equations describing the physical phenomena have been eliminated from the final formulae. Consequently, the model does not require the determination of parameters by means of difficult experimental measurements.

Ultrastructural and immunohistochemical study of the telencephalo-habenulo-interpeduncular connections of the goldfish.

Surgical ablations of telencephalon or telencephalon plus habenular nuclei (HBN) have been performed for studying anatomical connections of the telencephalo-habenulo-interpeduncular system of the goldfish. The results of the ultrastructural studies confirmed the presence of massive telencephalo-habenular and habenulo-interpeduncular projections and, in addition, demonstrated a minor direct telencephalo-interpeduncular connection. Immunohistochemical localization of substance P in the interpeduncular nucleus (IPN) after telencephalic ablation failed to demonstrate the involvement of this neurotransmitter in the direct telencephalo-interpeduncular projection, while telencephalon plus HBN ablation reduced substance P immunoreactivity in the IPN. The different distribution of degenerating terminals converging on the IPN from the HBN and from the telencephalon suggested a subnuclear organization of this area, as described in mammals.

A physical model for the cardiovascular and the respiratory systems.

We propose a two degrees of freedom oscillating system to simulate the working of both respiratory and cardiovascular apparatus and to investigate the physico-mathematical characteristics of a possible decoupling between the physiological systems. We suppose a double mathematical pendulum with forced and damped oscillations, with the first frequency equal to four times the second one; not only, does the system not give resonance or beatings, but it also simulates with reasonable approximation the ratio between natural relative frequencies. The two Langragian equations, that have form: (formula; see text) cannot be solved in an analytical way, even if we suppose an approximation for little oscillations. Now we are studying another two d-o-f mechanical system, with only one suspension point; we are also studying both the electrical equivalent circuits.

A stochastic process approach to the development of atheroma.

This study aims at formulating a dynamic model of particle sedimentation as applied to lipoprotein deposition during atheroma progression. The basic assumption is that all particles are identical and that the number of sedimented particles is relatively great. It is hypothised that sedimentation of a given particle is random; according to the theory of stochastic processes, the probability of a certain number of particles to sediment or deposit changes with time. The stochastic approach may explain some aspects of atherosclerosis development, i.e. its progression or regression.

[Ultrastructural changes in myocardial anoxia and reoxygenation]. / Modificazioni ultrastrutturali in corso di anossia miocardica e riossigenazione.

The aim of this study is to describe the ultrastructural changes in anoxic rat hearts perfused with Langendorff technique and the effects of reoxygenation on myocardial cells. After 1 h of aerobic perfusion, the hearts were subjected to 30 min of anoxia and then to 5 and 30 min of reoxygenation. The following findings were observed: after 30 min of anoxia, loss of mitochondrial matrix and dilatation of the intracristal spaces. After 5 min of reoxygenation: diffuse mitochondrial swelling, sarcomeres disarranged and out of register, several contraction bands. After 30 min: no evidence of cytoplasmic or mitochondrial swelling. The maximum enzyme release was observed when a wide myofibrillar contraction occurred. These results may suggest that the oxygen availability consequent to myocardium anoxia lead to further cell damage.

[Ribosome crystallization in the in vitro differentiation of chick embryo epidermis]. / La cristallizzazione ribosomiale nel differenziamento in vitro di epidermide di embrione di pollo.

Six day chick embryo thigh skin has been incubated for 2, 3 or 6 days in media containing either chick embryo extract or chick serum, than submitted to hypothermia for 36 hours to induce the formation of ribosome crystals. The results show that it is possible to relate the crystallization with the different degree of differentiation attained in each experimental condition.

[Ribosomal crystallization in the in vitro differentiation of mesenchymal cells interacting with the epithelium]. / La cristallizzazione ribosomiale nel differenziamento in vitro delle cellule mesenchimali interagenti con l'epitelio.

Ribosomal crystallization of 6-day chick embryo thigh skin in vitro in two different nutrient media was studied. The embryo thigh skin has been incubated for 3 or 6 days in media containing either chick embryo extract or chick serum, than submitted to hypothermia for 36 hours to induce the formation of ribosome crystals. The crystals are present in almost all type of cells in E medium, while in the cells in CS medium only after 3 days; therefore it is possible to relate the crystallization with the different degree of differentiation attained in mesenchymal cells.

[Presence of microtubular and filamentous structures in frequent association with ribosomal crystals]. / Presenza di strutture microtubulari e filamentose in frequente associazione con cristalli ribosomiali.

The contact of tubular bodies and cytofilaments with ribosome microcrystals from chick embryos incubated at 5 degrees C, was investigated by negative staining. It is revealed that for a good observation the time of fixation in glutaraldehyde was a critical point. It is suggested that tubular bodies and cytofilaments are engaged in the transport of ribosomes and ribosome tetramers.

[Obtaining ribosome crystals in homogenates]. / Ottenimento di cristalli ribosomiali in omogenato.

Chick embryos are homogenized in order to analyse ribosome crystallization. Ribosome crystallization has been induced by hypothermic treatment in chick embryos homogenate. Tetramers and crystals were produced by gradually inducing the temperature over a span of 10 h to 4 degrees C. It has been observed that the concentration of KCl in the buffer is a critical point. It is suggested that the nuclear fraction is engaged in ribosome crystallization.

[Effects of ionizing radiations on the ultrastructure of bursa of Fabricius]. / Effetti delle radiazioni ionizzanti sulla ultrastruttura della borsa di Fabrizio.

The alterations induced in the lymphoid and epitelial cells of the Bursa of Fabricius in chicks exposed at different doses of gamma rays mainly occur during the interfase. The extent of these alterations appears reduced in comparison with that observed in the chick thymus treated in the same way.

[Effects of ionizing radiations on the ultrastructure of the thymus gland]. / Effetti delle radiazioni ionizzanti sulla ultrastruttura del timo.

Different doses of gamma rays induce ultrastructural alterations in limphoid and epithelial cells of the chick thymus which exhibit a different temporal evolution after the treatment. The main changes which occur in lymphoid cells treated with 50 rads disappear 48 hours after the irradiation, while with 100 rads the radiation damage is still evident in epithelial cells.

An ultrastructural analysis of chick embryonic skin development in vitro.

Behaviour of 6-day chick embryo thigh skin in vitro in two different nutrients was studied electron microscopically. In explants supported with chicken serum containing medium epithelium keratinized faster than and in a similar way to that in ovo, except for the absence of corpuscola cribriformia in pericytes. It did not in explants supported with chick embryo extract containing medium, but underwent a noticeable ultrastructural evolution, mainly of granular reticulum and Golgi complexes. In the two series of cultures mesenchyme presented the same ultrastructural characteristics, especially as far as collagen fibers were concerned. The above data rule out the suggested regulatory role of collagen fibers in epidermal differentiation and support a possible epidermal two-step differentiative process. They are discussed in relation to the general mechanisms implicated in skin evolution.