In Vivo Biological Behavior of Polymer Scaffolds of Natural Origin in the Bone Repair Process

Autologous bone grafts, used mainly in extensive bone loss, are considered the gold standard treatment in regenerative medicine, but still have limitations mainly in relation to the amount of bone available, donor area, morbidity and creation of additional surgical area. This fact encourages tissue engineering in relation to the need to develop new biomaterials, from sources other than the individual himself. Therefore, the present study aimed to investigate the effects of an elastin and collagen matrix on the bone repair process in critical size defects in rat calvaria. The animals (Wistar rats, n = 30) were submitted to a surgical procedure to create the bone defect and were divided into three groups: Control Group (CG, n = 10), defects filled with blood clot; E24/37 Group (E24/37, n = 10), defects filled with bovine elastin matrix hydrolyzed for 24 h at 37 °C and C24/25 Group (C24/25, n = 10), defects filled with porcine collagen matrix hydrolyzed for 24 h at 25 °C. Macroscopic and radiographic analyses demonstrated the absence of inflammatory signs and infection. Microtomographical 2D and 3D images showed centripetal bone growth and restricted margins of the bone defect. Histologically, the images confirmed the pattern of bone deposition at the margins of the remaining bone and without complete closure by bone tissue. In the morphometric analysis, the groups E24/37 and C24/25 (13.68 ± 1.44; 53.20 ± 4.47, respectively) showed statistically significant differences in relation to the CG (5.86 ± 2.87). It was concluded that the matrices used as scaffolds are biocompatible and increase the formation of new bone in a critical size defect, with greater formation in the polymer derived from the intestinal serous layer of porcine origin (C24/25).     

Role of vitreous matrix on the optical activity of Ge-doped silica

We report an experimental study on the relationship between the optical activity of Ge-oxygen deficient centers and dynamic properties and conformational heterogeneity of vitreous matrix in silica. We focus our attention on the absorption band at ∼5.2 eV (B_2β) and on the two related emissions at ∼4.2 eV (α_E) and at ∼3.1 eV (β). From the temperature dependence of B_2β band we estimate a mean energy value of 26 meV for local vibrational modes coupled to the electronic transition, suggesting that the chromophore and its surrounding have access to low frequency dynamics. From the thermal behavior of the two emissions we distinguish the two competitive relaxation processes from the first singlet excited state S₁: the radiative one, giving rise the α_E band, and the thermally activated intersystem-crossing process between S₁ and the triplet state T₁, originating the β band. The intersystem-crossing rate increases on increasing the temperature, determining an opposite thermal behavior of the intensity of the two emissions. However, this temperature dependence cannot be rationalized by a simple Arrhenius law and the α_E decay kinetics at high temperatures do not follow a single exponential law, suggesting a complex landscape of configurational energies of the process.     

Error bounds for strongly convex programs and (super)linearly convergent iterative schemes for the least 2-norm solution of linear programs

Given an arbitrary point (x, u) inR ⁿ × R ₊ ^m , we give bounds on the Euclidean distance betweenx and the unique solution to a strongly convex program in terms of the violations of the Karush-Kuhn-Tucker conditions by the arbitrary point (x, u). These bounds are then used to derive linearly and superlinearly convergent iterative schemes for obtaining the unique least 2-norm solution of a linear program. These schemes can be used effectively in conjunction with the successive overrelaxation (SOR) methods for solving very large sparse linear programs.Sponsored by the United States Army under Contract No. DAAG29-80-C-0041. This material is based on research sponsored by National Science Foundation Grant No. DCR-8420963 and Air Force Office of Scientific Research Grant No. AFOSR-ISSA-85-00080.On leave from CRAI, via Bernini 5, Rende, Cosenza, Italy.     

The projection operator approach to the Fokker-Planck equation. II. Dichotomic and nonlinear Gaussian noise

Two models for the Freedericksz transition in a fluctuating magnetic field are considered: one is based on a dichotomic and the other on a nonlinear Gaussian noise. Both noises are characterized by a finite correlation time. It is shown that the linear response assumption leading to the best Fokker-Planck approximation in the dichotomic and nonlinear Gaussian cases can be trusted only up to the order ¹ and ⁰, respectively. The role of the corrections to the linear response approximation is discussed and it is shown how to replace the non-Fokker-Planck terms stemming from these corrections with equivalent terms of standard type. This technique is shown to produce perfect agreement with the exact analytical results (dichotomic noise) and to satisfactorily fit the results of analog simulation (nonlinear Gaussian noise).     

The projection approach to the Fokker-Planck equation. I. Colored Gaussian noise

It is shown that the Fokker-Planck operator can be derived via a projection-perturbation approach, using the repartition of a more detailed operator into a perturbation ₁ and an unperturbed part ₀. The standard Fokker-Planck structure is recovered at the second order in ₁, whereas the perturbation terms of higher order are shown to provoke the breakdown of this structure. To get rid of these higher order terms, a key approximation, local linearization (LL), is made. In general, to evaluate at the second order in ₁ the exact expression of the diffusion coefficient which simulates the influence of a Gaussian noise with a finite correlation time, a resummation up to infinite order in must be carried out, leading to what other authors call the best Fokker-Planck approximation (BFPA). It is shown that, due to the role of terms of higher order in ₁, the BFPA leads to predictions on the equilibrium distributions that are reliable only up to the first order in t. The LL, on the contrary, in addition to making the influence of terms of higher order in ₁ vanish, results in a simple analytical expression for the term of second order that is formally coincident with the complete resummation over all the orders in t provided by the Fox theory. The corresponding diffusion coefficient in turn is shown to lead in the limiting case to exact results for the steady-state distributions. Therefore, over the whole range 0 the LL turns out to be an approximation much more accurate than the global linearization proposed by other authors for the same purpose of making the terms of higher order in ₁ vanish. In the short- region the LL leads to results virtually coincident with those of the BFPA. In the large- region the LL is a more accurate approximation than the BFPA itself. These theoretical arguments are supported by the results of both analog and digital simulation.     

Targeting apoptosis via chemical design: inhibition of bid-induced cell death by small organic molecules

Bid is a key member of the Bcl-2 family proteins involved in the control of the apoptotic cascade in cells, leading to cell death. Uncontrolled cell death is associated with several human pathologies, such as neurodegenerative diseases and ischemic injuries. Therefore, Bid represents a potential yet unexplored and challenging target for strategies aimed at the development of therapeutic agents. Here we show that a multidisciplinary NMR-based approach that we named SAR by ILOEs (structure activity relationships by interligand nuclear Overhauser effect) allowed us to rationally design a series of 4-phenylsulfanyl-phenylamine derivatives that are capable of occupying a deep hydrophobic crevice on the surface of Bid. These compounds represent the first antiapoptotic small molecules targeting a Bcl-2 protein as shown by their ability to inhibit tBid-induced SMAC release, caspase-3 activation, and cell death.     

Synthesis, structure, and kinetics and stereochemistry of base-catalyzed hydrolysis of meso- and rac-[Co2(tmpdtne)Cl2]4+, bis(pentaamine) complexes devoid of deprotonatable NH centers

The bis(pentadentate) ligand tmpdtne binds two Co(II) centers, and the entity is readily oxidized to the dicobalt(III) derivative [Co(2)(tmpdtne)Cl(2)](4+) which has been separated into two isomeric forms. NMR studies establish these as meso and rac isomers arising from the different or same absolute configurations for the asym configuration about each Co(III) center. Each dinuclear ion base hydrolyses to the dihydroxo derivative [Co(2)(tmpdtne)(OH)(2)](4+) with retained asym configurations about each metal ion and also retained rac or meso configurations. The kinetics for the stepwise loss of the two Cl(-) ligands is uniphasic, and data are presented to show that the loss of the first chloride is rate determining and is followed by very rapid intramolecular and loss of the second Cl(-) via a hydroxo-bridged species to yield the observed dihydroxo derivative. Meso and rac forms of the latter have been crystallized. The X-ray crystal structure of the rac-dihydroxo complex is reported, and it establishes the configurations of all the complexes reported. The (1)H NMR spectra for the hydroxo ions show very high field Co-OH resonances (ca. delta-0.5 ppm) not observed previously for such ions, and this result is discussed in the context of published (1)H NMR data for bridged Co-OH-Co species. The base hydrolysis kinetics for the dichloro ions are first order in [OH(-)], and deprotonation at an alpha-CH(2) center (alpha to a pyridyl) is identified as the source of the catalysis, since there is no NH center available for deprotonation on the ligand. These data further support the new pseudoaminate base hydrolysis mechanism first reported in 2003. The values of k(OH) for the second-order base-catalyzed reaction are ca. 4.0 M(-1) s(-1) for both the rac and meso isomers, and these results are discussed in terms of the increased acidities of these 4+ cations compared to their 2+ ion counterparts.     

A New Route to Crystalline Salts of the Hydrolytic Dimer of Chromium(III)

Crystalline salts of the hydrolytic dimer of Cr(III), [Cr₂(μ-OH)₂(H₂O)₈]X₄·n H₂O (X = p-toluenesulfonate (tos) or mesitylene-2-sulfonate (dmtos)) have been prepared in good yields via a simple two-step procedure: H⁺ oxidation of Cr metal to give Cr²⁺ (T ≈? 70°) followed by O₂ oxidation, of Cr²⁺ to give the dimer (T ≈? 25°). The mechanism of conversion of Cr²⁺ into the dimer is discussed.     

Painleve' analysis of a variable coefficient Sine-Gordon equation

In this paper we study a variable coefficient Sine-Gordon (vSG) equation given by theta(tt)-theta(xx)+F(x,t)sin theta=0 where F(x,t) is a real function. To establish if it may be integrable we have performed the standard test of Weiss, Tabor, and Carnevale (WTC). We have got that the (vSG) equation has the Painleve' property (Pp) if the function F(x,t) satisfies a well-defined nonlinear partial differential equation. We have found the general solution of this last equation and, consequently, the functions F(x,t) such that the (vSG) equation possesses the (Pp), are given by F(x,t)=F(1)(x+t)F(2)(x-t) where F(1)(x+t) and F(2)(x-t) are arbitrary functions. Using this last result we have obtained some particular solutions of the vSG equation. (c) 1995 American Institute of Physics.