Ionic modification of calcium phosphate cement viscosity. Part I: hypodermic injection and strength improvement of apatite cement

A broadening of the indications for which calcium phosphate cements (CPC) can be used, for example, in the field of vertebroplasty, would require injectable and higher strength materials. Unmodified CPC are not injectable due to a filter-pressing effect during injection. In this work we demonstrated that an effective method for improving the injection properties of CPC was by the use of sodium citrate solution as a liquid component. Cement consisting of tetracalcium phosphate (TTCP) and monetite (DCPA) mixed with water up to a powder:liquid ratio (P:L) of 3.3 g/ml had an injectability of approximately 60%. The use of 500 mM trisodium citrate solution instead of water decreased the viscosity of the cement paste to a point, where complete injectability (>95%) through an 800 microm diameter hypodermic needle could be achieved at low loads. The reduction in water demand of the cement effected by the use of sodium citrate enabled high P:L mixes to be formed which were 400% stronger than cements made with water. The effect was less pronounced with compacted cements such that at 9 MPa applied pressure, 58% improvement was obtained and at 50 MPa 36% improvement was measured yielding a cement with a compressive strength of 154 MPa. The liquefying effect of sodium citrate was thought to derive from a strong increase in the surface charge of both the reactants and the product as determined by zeta-potential measurement.     

A multidisciplinary clinic for individualizing management of patients at increased risk for breast and gynecologic cancer

Increasing awareness of the hereditary component of breast and ovarian cancer has driven interest in creating clinics for the patient population at high risk for these cancers. Identifying adequate space and appropriate staff, coordinating multiple providers’ schedules, establishing referral criteria, and addressing billing and reimbursement concerns are just some of the issues that are involved in the creation of a multidisciplinary high risk breast and ovarian cancer program. We provide an overview of the clinic structure at the Magee-Womens Hospital High Risk Breast and Ovarian Cancer Program (HRBOCP), which was created in 2002 due to recognition of a need for a more coordinated model of providing care for women at increased risk for breast and ovarian cancer. The goals of the HRBOCP are to evaluate women at high risk for breast and ovarian cancer and to organize their clinical care in a multidisciplinary setting staffed by experts in the field; to provide updates on new data regarding screening recommendations, prevention options, and risk factors pertinent to an individual’s cancer risk; to provide ongoing support to patients and to coordinate family communication when appropriate; and to facilitate enrollment in appropriate research studies and registries.     

Controlled release of gentamicin from calcium phosphate-poly(lactic acid-co-glycolic acid) composite bone cement

Modification of a self setting bone cement with biodegradable microspheres to achieve controlled local release of antibiotics without compromising mechanical properties was investigated. Different biodegradable microsphere batches were prepared from poly(lactic-co-glycolic acid) (PLGA) using a spray-drying technique to encapsulate gentamicin crobefate varying PLGA composition and drug loading. Microsphere properties such as surface morphology, particle size and antibiotic drug release profiles were characterized. Microspheres were mixed with an apatitic calcium phosphate bone cement to generate an antibiotic drug delivery system for treatment of bone defects. All batches of cement/microsphere composites showed an unchanged compressive strength of 60 MPa and no increase in setting time. Antibiotic release increased with increasing drug loading of the microspheres up to 30% (w/w). Drug burst of gentamicin crobefate in the microspheres was abolished in cement/microsphere composites yielding nearly zero order release profiles. Modification of calcium phosphate cements using biodegradable microspheres proved to be an efficient drug delivery system allowing a broad range of 10-30% drug loading with uncompromised mechanical properties.     

Rheological enhancement of mechanically activated alpha-tricalcium phosphate cements

Most biocements are two- or three-component acid-based systems with large differences in the component particle sizes, which occurs by virtue of the differing processing routes. This work aimed to improve injectability and strength of a single reactive component cement, that is, mechanically activated alpha-tricalcium phosphate (TCP)-based cement by adding 13-33 wt % of several fine-particle-sized (d(50) of 0.5-1.1 microm) fillers [dicalcium phosphate anhydrous (DCPA), titanium dioxide (TiO(2)), and calcium carbonate] to the monomodal alpha-TCP matrix (d(50) = 9.8 microm). A high zeta-potential was measured for all particles in trisodium citrate solution. The fraction of alpha-TCP cement "injected" through an 800-microm hypodermic needle was found to be only 35% at a powder-to-liquid ratio of 3.5 g/mL. In contrast, the use of fillers decreased cement viscosity to a point, where complete injectability could be obtained. Mechanistically, these additives disrupted alpha-TCP particle packing yet decreased the interparticle spacing by a factor of approximately 5.5 such that the electrostatic repulsion effect was enhanced. A strength improvement was found when DCPA and TiO(2) were used as fillers despite the lower degree of conversion of these cements. Compressive strengths of precompacted cement samples increased from 70 MPa for unfilled alpha-TCP cement to 140 (110) MPa for 23 wt % DCPA (or TiO(2)) fillers as a result of porosity reduction. Strength improvement for more clinically relevant uncompacted cements was achieved by higher powder-to-liquid ratio mixes for filled cements such that maximum strengths of 90 MPa were obtained for 23 wt % DCPA filler compared with 50 MPa for single-component alpha-TCP cement.     

Substituted Xanthones as Selective and Reversible Monoamine Oxidase A (MAO-A) Inhibitors

l,3-Dihydroxy-2-methylxanthone (XI), its 4-chloro and 4-bromo derivatives (X1-C1 and Xl-Br), and 1 ,3-dihydroxy-4-methylxanthone were investigated for their inhibition activities toward MAO. A hyperbolic function was derived to fit the data and to calculate IC₅₀ values. The compounds proved to be reversible and selective inhibitors of MAO-A, with XI displaying the highest activity (IC₅₀ = 3.7 µM).     

Regulated expression of vasopressin gene by cAMP and phorbol ester in primary rat fetal hypothalamic cultures.

Using dispersed cultures of fetal rat hypothalami, we studied the effects of forskolin and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), activators of protein kinase A and C, respectively, upon vasopressin (VP) secretion, VP mRNA expression and VP mRNA poly(A) tail length. Forskolin stimulated the VP mRNA content and peptide secretion 2.6-fold and induced an increase in the poly(A) tail length of approximately 90 nucleotides. TPA induced an increase in VP mRNA size and stimulated 1.9-fold the secretion of VP without an increase in VP mRNA content. Depolarization with potassium induced an increase in the VP peptide secreted of 2.2-fold, with no effect on the VP mRNA content or size. Increased osmolality had no effect on either VP peptide or VP mRNA. We conclude that VP expression in cultured fetal rat hypothalamic cells is regulated via both protein kinase A and protein kinase C pathways.     

Second messengers involved in the regulation of corticotropin-releasing hormone mRNA and peptide in cultured rat fetal hypothalamic primary cultures

Using primary cultures of dispersed rat fetal hypothalami, we studied the effect of forskolin and the phorbol ester 12-o-tetradecanoyl phorbol 13-acetate, activators of protein kinase A and C, respectively, on corticotropin-releasing hormone (CRH) regulation. CRH mRNA accumulation and peptide release were stimulated by both agents, indicating that the protein kinase A and protein kinase C messenger systems are involved in the regulation of CRH gene expression and are functional in hypothalamic neurons isolated from fetal brain.     

Das Ossifikationsprinzip der Trachealknorpel. Röntgenologisch-morphometrische und experimentelle Untersuchungen

Summary The ossification of human tracheal cartilage is thought to be degenerative or due to genetic factors; in the final resort, however, its etiology still remains to be clarified. Therefore, on the one hand tracheal cartilages obtained from corpses of both sexes and various ages were X-rayed and subjected to measurements at defined points and, on the other hand, the relative distribution of stresses within tracheal cartilage was investigated in a model, using wire strain gauges, and evaluated with the aid of a computer. With increasing age, the cross-section of the tracheal cartilage at the sides and in the middle becomes greater, but to varying extents. Furthermore, in 50% of the males and in only 5% of the females, ossification with lamellar spongiosa occurs, primarily in the cranial and caudal outer margins of the ventral part of the cartilage ring. The cartilage, which is constantly subjected to tensile and compressive forces, reacts with an adaptive hypertrophy at that part of the inside of the cartilage that is exposed predominantly to compressive loading. As a result, the middle of the cartilage is markedly thicker than the sides. Under the influence of the compressive forces, the band-like traction effect of the collagen fibres in the ventral subperichondrial region of the tracheal cartilage becomes insufficient and the effects of stress on the cartilage greater. For a given stress level a greater extension results, which induces ossification in the region of its maximum effect — in the cranial and caudal convexity of the ventral part of the cartilage. In the region of ossification stabilization'occurs as a result of a change in the modulus of elasticity, so that the points subjected to the maximum extension force migrate laterally. In these sections, new bone is laid down until the tracheal cartilage has stiffened. The forces necessary to induce cartilaginous hypertrophy on the one hand, and insufficiency of the band-like traction effect on the other occur predominantly only in the male trachea. The ossification of tracheal cartilage is a further example of self-regulated adaptation of the connective and supportive tissues to mechanical stressing.

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Mit Unterstützung durch die DFG (SFB 118)     

Ergonomic evaluation of an ecological interface and a profilogram display for hemodynamic monitoring

Objective.Comprehensive monitoring of the patient state andsubsequent decision making is an essential part of the task of ananaesthetist. The physicians' decision making process is based upon aconcept of partly abstract physiologic parameters such as depth of anaesthesiaor contractility. This concept is derived from the measured parameters givenon todays' trend displays in addition to context information availablefor the anaesthetist. We investigated two alternative approaches of displaydesign for hemodynamic monitoring: 1) integrated displays based on ecologicalinterface design, and 2) profilogram displays based on intelligent alarms.Method.To evaluate differences in decision making, the two displaysand a trend display were compared in an experimental set-up with computersimulated vital parameter curves. From a start state with random parameterdeviations from the ideal state, subjects had to achieve the ideal circulatoryperformance as fast as possible by manipulating vasomotor tone, heart rate,blood volume and contractility. To analyse subjects' decision makingprocess, eye-tracking, event-logging, and the method of think aloud protocolswere used. Twenty anaesthesiologists performed 113 experiments (approximately2 with each display). Results.The anaesthetists failed to achieve thetask in 37% using the trend display, in 19% using the profilogram display, andin 13% using the ecological interface. Hence, a safer task solution waspossible with the ecological interface and the profilogram display but at theexpense of various performance parameters such as higher trial time, moreinteractions with the simulated system, and more frequent eye movements. Incontrast to the trend display and the profilogram display, where anaesthetistswere mainly focussed on controlling the left atrial pressure, such anbehaviour was less observed with the ecological interface. Conclusion.Our results have shown that subjects came to more effective solutions withthe traditional trend display. The main reason for this result may be theiryears of experience with this kind of display type. Regarding safe andgoal-intended decision finding, the results are encouraging for furtherexperiments with redesigned ecological displays. But these displays ought tohave smoother changes with respect to the traditional trend displays.Furthermore, new experiments have to be performed under real or fairly real(e.g. together with an anaesthesia simulator) conditions to underline thepositive results for ecological interfaces.