Nucleation parameters for polymer crystallization from non-isothermal thermal analysis

Differential scanning calorimetry (DSC) has been used to obtain kinetic and nucleation parameters for polymer crystallization under a non-isothermal mode of operation. The available isothermal nucleation growth-rate equation has been modified for non-isothermal kinetic analysis. The values of the nucleation constant (K g ) and surface free energies (sgr, sgr e ) have been obtained for i-polybutene-1, i-polypropylene, poly(L-lactic acid), and polyoxymethylene and are compared with those obtained from isothermal kinetic analysis; a good agreement in both is seen.

Novel insights on functions of myotilin/palladin family members

Poikkijuovaisen luuranko- ja sydänlihaksen supistumisyksikkö, sarkomeeri, koostuu tarkoin järjestyneistä aktiini- ja myosiinisäikeistä. Rakenne eroaa muista solutyypeistä, joissa aktiinisäikeistö muovautuu jatkuvasti ja sen järjestyminen säätelee solun muotoa, solujakautumista, soluliikettä ja solunsisäisten organellien kuljetusta. Myotilin, palladin ja myopalladin kuuluvat proteiiniperheeseen, jonka yhteispiirteenä ovat immunoglobuliinin kaltaiset (Igl) domeenit. Proteiinit liittyvät aktiinitukirankaan ja niiden arvellaan toimivan solutukirangan rakenne-elementteinä ja säätelijöinä. Myotilinia ja myopalladinia ilmennetään poikkijuovaisessa lihaksessa. Sen sijaan palladinin eri silmukointimuotoja tavataan monissa kudostyypeissä kuten hermostossa, ja eri muodoilla saattaa olla solutyypistä riippuvia tehtäviä. Poikkijuovaisessa lihaksessa kaikki perheen jäsenet sijaitsevat aktiinisäikeitä yhdistävässä Z-levyssä ja ne sitovat Z-levyn rakenneproteiinia, -aktiniinia. Myotilingeenin pistemutaatiot johtavat periytyviin lihastauteihin, kun taas palladinin mutaatioiden on kuvattu liittyvän periytyvään haimasyöpään ja lisääntyneeseen sydäninfarktin riskiin. Tässä tutkimuksessa selvitettin myotilinin ja pallainin toimintaa. Kokeissa löydettiin uusia palladinin 90-92kDa alatyyppiin sitoutuvia proteiineja. Yksi niistä on aktiinidynamiikkaa säätelevä profilin. Profilinilla on kahdenlaisia tehtäviä; se edesauttaa aktiinisäikeiden muodostumista, mutta se voi myös eristää yksittäisiä aktiinimolekyylejä ja edistää säikeiden hajoamista. Solutasolla palladinin ja profilinin sijainti on yhtenevä runsaasti aktiinia sisältävillä solujen reuna-alueilla. Palladinin ja profilinin sidos on heikko ja hyvin dynaaminen, joka sopii palladinin tehtävään aktiinisäideiden muodostumisen koordinoijana. Toinen palladinin sitoutumiskumppani on aktiinisäikeitä yhteensitova -aktiniini. -Aktiniini liittää solutukirangan solukalvon proteiineihin ja ankkuroi solunsisäisiä viestintämolekyylejä. Sitoutumista välittävä alue on hyvin samankaltainen palladinissa ja myotilinissa. Luurankolihaksen liiallinen toistuva venytys muuttaa Z-levyjen rakennetta ja muotoa. Prosessin aikana syntyy uusia aktiinifilamenttejä sisältäviä tiivistymiä ja lopulta uusia sarkomeereja. Löydöstemme perusteella myotilinin uudelleenjärjestyminen noudattaa aktiinin muutoksia. Tämä viittaa siihen, että myotilin liittää yhteen uudismuodostuvia aktiinisäikeitä ja vakauttaa niitä. Myotilin saattaa myös ankkuroida viesti- tai rakennemolekyylejä, joiden tehtävänä on edesauttaa Z-levyjen uudismuodostusta. Tulostemme perusteella arvelemme, että myotilin toimii Z-levyjen rakenteen vakaajana ja aktiinisäikeiden säätelijänä. Palladinin puute johtaa sikiöaikaiseen kuolemaan hiirillä, mutta myotilinin puutoksella ei ole samanlaisia vaikutuksia. Tuotettujen myotilin poistogeenisten hiirten todetiin syntyvän ja kehittyvän normaalisti eikä niillä esiintynyt rakenteellisia tai toiminnallisia häiriöitä. Toisaalta aiemmissa kokeissa, joissa hiirille on siirretty ihmisen lihastautia aikaansaava myotilingeeni, nähdään samankaltaisia kuin sairailla ihmisillä. Näin ollen muuntunut myotilin näyttä olevan lihaksen toiminnalle haitallisempi kuin myotilinin puute. Myotilinin ja palladinin yhteisvaikutusta selvittääksemme risteytimme myotilin poistegeenisen hiiren ja hiirilinjan, joka ilmentää puutteellisesti palladinin 200 kDa muotoa. Puutteellisesti 200 kDa palladinia ilmentävien hiirten sydänlihaksessa todettiin vähäisiä hienorakenteen muutoksia, mutta risteytetyillä hiirillä tavattiin rakenteellisia ja toiminnallisia muutoksia myös luurankolihaksessa. Tulosten perusteella voidaan todeta, että palladinin 200 kDa muoto säätelee sydänlihassolujen rakennetta. Luurankolihaksessa sen sijaan myotilinilla ja palladinilla näyttäisi olevan päällekkäisiä tehtäviä.

Conformational analysis of D-pantothenic acid

The conformational analysis of d-pantothenic acid using classical semiempirical methods has been carried out. The pantothenic acid molecule can exist in the neutral form (I) or in the ionised form (II) with a deprotonated negatively charged carboxyl group. The neutral molecule as well as the anion is highly flexible and has an ensemble of several allowed conformations rather than one or two unique conformations. The distribution of allowed conformations indicate that the β-alanine as well as the pantoic acid part of the molecule prefers partially folded conformations. The conformation of the former is greatly affected by the ionisation state of the carboxyl group whereas that of the latter is not. Possibility of intramolecular hydrogen bonding in different allowed conformations has also been explored. A bifurcated hydrogen bond involving a carboxyl (or carboxylate) oxygen atom and a hydroxyl oxygen atom, as acceptors, and the amide nitrogen atom as the donor occurs frequently in both I and II. Amongst the two crystal structures containing pantothenic acid reported so far, the conformation of the molecule in l-lysine d-pantothenate lies in the allowed region and is stabilised by a bifurcated intramolecular hydrogen bond, whereas that in the calcium bromide salt falls in a disallowed region, presumably due to the requirement of tridentate metal coordination.

Arginine Decarboxylase from Lathyrus sativus Seedlings Purification and Properties

Arginine decarboxylase which makes its appearance in Lathyrus sativus seedlings after 24 h of seed germination reaches its highest level around 5–7 days, the cotyledons containing about 60% of the total activity in the seedlings at day 5. The cytosol enzyme was purified 977-fold from whole seedlings by steps involving manganese chloride treatment, ammonium sulphate and acetone fractionations, positive adsorption on alumina C-γ gel, DEAE-Sephadex chromatography followed by preparative disc gel electrophoresis. The enzyme was shown to be homogeneous by electrophoretic and immunological criteria, had a molecular weight of 220000 and appears to be a hexamer with identical subunits. The optimal pH and temperature for the enzyme activity were 8.5 and 45 °C respectively. The enzyme follows typical Michaelis-Menten kinetics with a Km value of 1.73 mM for arginine. Though Mn2+ at lower concentrations stimulated the enzyme activity, there was no dependence of the enzyme on any metal for the activity. The arginine decarboxylase of L. sativus is a sulfhydryl enzyme. The data on co-factor requirement, inhibition by carbonyl reagents, reducing agents and pyridoxal phosphate inhibitors, and a partial reversal by pyridoxal phosphate of inhibition by pyridoxal · HCl suggests that pyridoxal 5'-phosphate is involved as a co-factor for the enzyme. The enzyme activity was inhibited competitively by various amines including the product agmatine. Highest inhibition was obtained with spermine and arcain. The substrate analogue, l-canavanine, homologue l-homoarginine and other basic amino acids like l-lysine and l-ornithine inhibited the enzyme activity competitively, homoarginine being the most effective in this respect.

Applications of coralline hydroxyapatite with bioabsorbable containment and reinforcement as bone graft substitute : An experimental study

The aim of the present experimental study was to find out if the applications of coralline hydroxyapatite (HA) can be improved by using bioabsorbable containment or binding substance with particulate HA in mandibular contour augmentation and by using bioabsorbable fibre-reinforced HA blocks in filling bone defects and in anterior lumbar interbody fusion. The use of a separate curved polyglycolide (PGA) containment alone or together with a fast resorbing polyglycolide/polylactide (PGA/PLA) binding substance were compared to the conventional non-contained method in ridge augmentation in sheep. The contained methods decreased HA migration, but the augmentations did not differ significantly. The use of the containment caused a risk for wound dehiscence and infection. Histologically there was a rapid connective tissue ingrowth into the HA graft and it was more abundant with the PGA containment compared to the non-contained augmentation and even additionally rich when the HA particles were bound with PGA/PLA copolymer. However, the bone ingrowth was best in the non-contained augmentation exceeding 10-12 % of the total graft area at 24 weeks. Negligible or no bone ingrowth was seen in the cases where the polymer composite was added to the HA particles and, related to that, foreign-body type cells were seen at the interface between the HA and host bone. The PGA and poly-dl/l-lactide (PDLLA) fibre-reinforced coralline HA blocks were studied in the metaphyseal and in the diaphyseal defects in rabbits. A rapid bone ingrowth was seen inside the both types of implants. Both PGA and PDLLA fibres induced an inflammatory fibrous reaction around themselves but it did not hinder the bone ingrowth. The bone ingrowth pattern was directed according to the loading conditions so that the load-carrying cortical ends of the implants as well as the implants sited in the diaphyseal defects were the most ossified. The fibre-reinforced coralline HA implants were further studied as stand-alone grafts in the lumbar anterior interbody implantation in pigs. The strength of the HA implants proved not to be adequate, the implants fractured in six weeks and the disc space was gradually lost similarly to that of the discectomized spaces. Histologically, small quantities of bone ingrowth was seen in some of the PGA and PDLLA reinforced coralline implants while no bone formation was identified in any of the PDLLA reinforced synthetic porous HA implants. While fragmented, the inner structure of the implants was lost, the bone ingrowth was minimal, and the disc was replaced by the fibrous connective tissue. When evaluated radiologically the grade of ossification was assessed as better than histologically, and, when related to the histologic findings, CT was more dependable than the plain films to show ossification of the implanted disc space. Local kyphosis was a frequent finding along with anterior bone bridging and ligament ossification as a consequence of instability of the implanted segment.

Bioabsorbable materials for osteosynthesis and small joint arthroplasty in the hand

Fractures and arthritic joint destruction are common in the hand. A reliable and stable fracture fixation can be achieved by metal implants, which however, become unnecessary or even harmful after consolidation. The silicone implant arthroplasty is the current method of choice for reconstruction of metacarpophalangeal joints in rheumatoid patients. However, the outcome tends to worsen with long-term follow-up and implant-related complications become frequent. To address these problems, bioabsorbable implants were designed for the hand area. Aims of the studies were: 1) to evaluate the biomechanical stabilities provided by self- reinforced (SR) bioabsorbable implants in a transverse and an oblique osteotomy of small tubular bones and to compare them with those provided by metal implants; 2) to evaluate the SR poly-L/DL-lactide 70/30 plate for osteosynthesis in a proof-of-principle type of experiment in three cases of hand injuries; and 3) to evaluate the poly-L/D-lactide (PLA) 96/4 joint scaffold, a composite joint implant with a supplementary intramedullary Polyactive® stem and Swanson silicone implant in an experimental small joint arthroplasty model. Methods used were: 1) 112 fresh frozen human cadaver and 160 pig metacarpal bones osteotomised transversally or obliquely, respectively, and tested ex vivo in three point bending and in torsion; 2) three patient cases of complex hand injuries; and 3) the fifth metacarpophalangeal joints reconstructed in 18 skeletally-mature minipigs and studied radiologically and histologically. The initial fixation stabilities provided by bioabsorbable implants in the tubular bones of the hand were comparable with currently-employed metal fixation techniques, and were sufficient for fracture stabilisation in three preliminary cases in the hand. However, in torsion the stabilities provided by bioabsorbable implants were lower than that provided by metal counterparts. The bioabsorbable plate enhanced the bending stability for the bioabsorbable fixation construct. PLA 96/4 joint scaffolds demonstrated good biocompatibility and enabled fibrous tissue in-growth in situ. After scaffold degradation, a functional, stable pseudarthrosis with dense fibrous connective tissue was formed. However, the supplementary Polyactive® stem caused a deleterious tissue reaction and therefore the stem can not be applied to the composite joint implant. The bioabsorbable implants have potential for use in clinical hand surgery, but have to await validation in clinical patient series and controlled trials.

Structural basis for the catalytic mechanism of homoserine dehydrogenase

Homoserine dehydrogenase (HSD) is an oxidoreductase in the aspartic acid pathway. This enzyme coordinates a critical branch point of the metabolic pathway that leads to the synthesis of bacterial cell-wall components such as L-lysine and m-DAP in addition to other amino acids such as L-threonine, L-methionine and L-isoleucine. Here, a structural rationale for the hydride-transfer step in the reaction mechanism of HSD is reported. The structure of Staphylococcus aureus HSD was determined at different pH conditions to understand the basis for the enhanced enzymatic activity at basic pH. An analysis of the crystal structure revealed that Lys105, which is located at the interface of the catalytic and cofactor-binding sites, could mediate the hydride-transfer step of the reaction mechanism. The role of Lys105 was subsequently confirmed by mutational analysis. Put together, these studies reveal the role of conserved water molecules and a lysine residue in hydride transfer between the substrate and the cofactor.

Polilaktida oinarri duten inplante polimeriko biodegradagarrien diseinu, fabrikazio eta propietateak

[EU]3D inprimaketa gaur egun, biomedikuntzaren garapenerako aukera ezberdinak ematen dituen teknologia iraultzaile gisa aurkezten da; bai medikuntza arloan formazio eta ikerkuntzarako erreminta gisa, baita dispositibo berrien diseinu eta fabrikaziorako. Bere abantailarik aipagarriena prototipaketa azkarra da. Gainera, teknologia honek barne egitura eta forma ezberdineko objektuak fabrikatzea ahalbidetzen du koste lehiakor batean. Lan honen helburua 3D inprimagailuen bidezko prototipoen fabrikazioan zentratzen da, horretarako lehengai bezala polimero biodegradagarri eta biobateragarria erabiliz. Horrez gain, metodo tradizionalarekin konparatuz teknologia honek izan ditzakeen abantailak ere aztertu nahi dira, ez bakarrik alde ekonomikoari edo denborari begira, baita fabrikatutako objektuen propietateei begira ere. Dena dela, horrekin hasi aurretik ezaugarritze fisiko eta termikoa burutu beharko zaie lehengaiei, 3D inprimagailuaren parametroen aukeraketa egokia egiteko eta parametro horien eta amaierako produktuaren kalitate, egitura eta propietateen artean erlazio egokia ezartzeko. Lan hau aurrera eramateko poli(L-laktida)-rekin (PLLA) egingo da lan, bai ehun ingeniaritzan baita hezurren apurketen finkapenerako dispositiboetan oso erabilia izan den polimeroa.

Inplante kirurgiko erradiopakoen bideragarritasuna: plla/bario sulfato sistemaren ``in vitro´´ degradazioa.

[EU]Polimero biobateragarri eta biodegradagarrien erabilera medikuntza arloan aurrerapauso handia suposatu du. Inplanteen arloan (torlojuak, iltzeak, plakak, eta abar…) eta ehun ingeniaritzan garrantzia handia dute. Hala ere, polimero hauen inplanteek desabantaila nabaria aurkezten dute ohiko material metalikoekin alderatuz: erradiopazitate eza. Ikerketa lan honetan karga erradiopako baten adizioak polimero biobateragarri eta biodegradagarri baten giza gorputzaren baldintzetan (pH=7,2 eta 37ºC) burututako in vitro degradazioan duen eragina aztertu da, %70 poli(L-laktida) (PLLA) eta %30 bario sulfato (BaSO4) sistemaren degradazioa, hain zuzen ere. Aztertutako karga erradiopakoak PLLAren degradazioan eragin handirik ez duela ondorioztatu da, beraz, sistema bideragarria dela.

HORMONAL-REGULATION OF TISSUE-TYPE PLASMINOGEN-ACTIVATOR AND PLASMINOGEN-ACTIVATOR INHIBITOR TYPE-1 IN CULTURED MONKEY SERTOLI CELLS

Sertoli cells play a central role in the control and maintenance of spermatogenesis. Isolated Sertoli cells of mouse and rat testes have been shown to secrete plasminogen activator (PA) and a plasminogen activator inhibitor type-1 (PAI-1) in culture. In this study, we have investigated the hormonal regulation of PA and PAI-1 activities in cultured monkey Sertoli cells. Sertoli cells (5x10(5) cells/well) isolated from infant rhesus monkey testes were preincubated at 35 degrees C for 16 h in 24-well plates precoated with poly(D-lysine) (5 mu g/cm(2)) in 0.5 mi McCoy's 5a medium containing 5% of fetal calf serum and further incubated for 48 h in 0.5 mi serum-free medium with or without various hormones or other compounds, PA as well as PAI-1 activities in the conditioned media were assayed by fibrin overlay and reverse fibrin autography techniques respectively. The Sertoli cells in vitro secreted only tissue-type PA (tPA), no detectable amount of urokinase-type PA (uPA) could be observed, Monkey Sertoli cells were also capable of secreting PAI-1, Immunocytochemical studies indicated that both tPA and PAI-1 positive staining localized in the Sertoli cells, spermatids and residual bodies of the seminiferous epithelium; Northern blot analysis further confirmed the presence of both tPA and PAI-1 mRNA in monkey Sertoli cells. Addition of follicle-stimulating hormone (FSH) or cyclic adenosine monophosphate (cAMP) derivatives or cAMP-generating agents and gonadotrophin-releasing hormone (GnRH) agonist or phorbol ester (PMA) to the cell culture significantly increased tPA activity. PAI-1 activity in the culture was also enhanced by these reagents except 8-bromo-dibutyryl-cAMP, forskolin and 3-isobutyl-1-methylxanthin (MIX) which greatly stimulated tPA activity, whereas decreased PAI-1 activity, implying that neutralization of PAI-1 activity by tile high level of tPA in the conditioned media may occur. These data suggest that increased intracellular signals which activate protein kinase A (PKA), or protein kinase C (PKC) can modulate Sertoli cell tPA and PAI-1 activities, The concomitant induction of PA and PAI-1 by the same reagents in the Sertoli cells may reflect a finely tuned regulatory mechanism in which PAI-1 could limit the excession of the proteolysis.

Effect of several feeding stimulants on diet preference by juvenile gibel carp (Carassius auratus gibelio), fed diets with or without partial replacement of fish meal by meat and bone meal

The objectives of this work were to study the effects of several feeding stimulants on gibel carp fed diets with or without replacement of fish meal by meat and bone meal (MBM). The feeding stimulants tested were betaine, glycine, L-lysine, L-methionine, L-phenylalanine, and a commercial squid extract. Three inclusion levels were tested for each stimulant (0.18, 0.5%, and 1% for betaine and 0.1, 0.25 and 0.5% for the other stimulants). Two basal diets (40% crude protein) were used. one with 26% fish meal (FM), and the other with 21% fish meal and 6% MBM, Betaine at 0.1% in the fish meal group and at 0.5% in the meat and bone meal group was used in all experiments for comparison among stimulants. In the experiment on each stimulant, six tanks of fish were equally divided into two groups, one fed the FM diet, and the other fed the MBM diet. After 7 days' adaptation to the basal diet, in which the fish were fed to satiation twice a day, the fish were fed for another 7 days an equal mixture of diets containing varying levels of stimulants. Each diet contained a unique rare earth oxide as inert marker (Y2O3, Yb2O3, La2O3, Sm2O3 or Nd2O3). During the last 3 days of the experiment, faeces from each tank were collected. Preference for each diet was estimated based on the relative concentration of each marker in the faeces. Gibel carp fed the FM diet had higher intake than those fed the MBM diet, but the difference was significant only in the experiments on betaine, glycine and L-methionine. None of the feeding stimulants tested showed feeding enhancing effects in FM diets. All feeding stimulants showed feeding enhancing effects in MBM diets. and the optimum inclusion level was 0.5% for betaine, 0.1% for glycine, 0.25% for L-lysine, 0.1% for L-methionine. 0.25% For L-phenylalanine. and 0.1% for squid extract. The squid extract had the strongest stimulating effect among all the stimulants tested. (C) 2001 Elsevier Science B.V. All rights reserved.

骨修复用纳米生物玻璃/聚乳酸复合材料的研究

本文首次制备了纳米生物玻璃左旋聚乳酸复合材料，并针对两者之间界面不相容的现象，对生物玻璃表面进行了有针对性的改性；对其纳米颗粒的分散能力进行了表征，并对复合材料的力学性能和生物相容性进行了研究，以期能得到一种具有良好力学性能和生物活性的可降解骨组织修复材料。 （1） 以正硅酸乙酯为硅源，以磷酸氢二铵为磷源，硝酸钙为钙源制备了纳米生物玻璃的凝胶颗粒(BAG, SiO2: CaO: P2O5 =37/54/9, mol/mol) ；以其表面的硅羟基为引发点，采用丙交酯开环聚合原位改性的方法对其进行了表面改性得到了改性纳米生物玻璃的凝胶颗粒（m-BAG）；通过改性，使其表面性质由亲水性变为亲油性，提高了其在聚乳酸基体内的分散能力；m-BAG/PLLA复合材料改变了改性以前BAG/PLLA力学性能随生物玻璃含量增加而不断下降的趋势，保持了聚乳酸的力学性能，在m-BAG含量为2%的时候其拉伸强度相对于纯聚乳酸提高16%左右，模量达到纯聚乳酸的1.4倍；而当m-BAG含量为10wt%，复合材料保持与纯聚乳酸相似的拉伸强度，而此时10wt%BAG/PLLA复合材料的力学性能只有纯聚乳酸的80%; 生物玻璃凝胶/聚乳酸复合材料在模拟体液中表现了较高的钙沉积能力，最后在其表面都形成了羟基磷灰石的晶体，但是表面改性使其钙沉积的速度降低，在一定程度上减小了其活性；细胞试验表明，不论生物玻璃凝胶/聚乳酸复合材料还是改性后的复合材料都表现出了很高的细胞黏附性能和增殖性能。 （2） 通过煅烧将生物玻璃的凝胶颗粒制备了生物玻璃纳米颗粒，通过XRD和TGA确定该组成类型的生物玻璃的结晶温度在826ºC，我们选择其经过600ºC煅烧的非晶态的材料作为我们进一步研究的对象。通过六次甲基异氰酸酯作为偶联剂，我们将低分子量的Mn=9,700Da的聚乳酸偶连到生物玻璃纳米颗粒的表面；通过改性提高了生物玻璃/聚乳酸的拉伸强度和拉伸模量，并提高了其分散能力；模拟体液试验表明，其复合材料具有很强的钙沉积能力，细胞培养证明了优异的生物相容性；而且通过试验可以看出，生物玻璃相对于其原始的纳米凝胶颗粒具有更优异的钙沉积能力和细胞相容性。 （3） 通过将三臂聚乳酸添加到线性聚乳酸的内部，大幅度的提高了其冲击强度，当三臂聚乳酸含量达到2wt%-8wt%时，冲击强度达到线性聚乳酸的2倍左右；通过偏光显微镜观察，可以看到三臂聚乳酸提高了线性聚乳酸的结晶成核速度，使其最后晶体数量增多，形态变小；而通过等温结晶试验表明其结晶速度提高，结晶是以异相成核的三维生长方式进行的；流变学试验表明加入三臂聚乳酸有力的降低了体系的复数粘度，当三臂聚乳酸含量达到8%时候，在频率为1-10rad/s其数值仅为线性聚乳酸的60%左右，这种变化将提高其加工成型能力。 （4） 通过十六烷基三甲基溴化铵作为模板剂，制备了具有多孔结构的生物玻璃纳米颗粒，其孔径在2nm左右，比表面积为264m2/g； 通过模拟体液试验表明，其具有很强的生物活性，规整结构在浸泡的前8小时被破坏，体系中P和Ca的含量大幅度上升，在24小时以后形成了羟基磷灰石的晶体。该类型的材料有望应用于制备药物缓释材料，用于骨修复初期的感染和炎症治疗。

可生物降解的两亲性嵌段共聚物的自聚集行为研究

可生物降解的两亲性嵌段共聚物PLA-PEG飞所制备的胶束或纳术粒子，作为潜在的药物控制释放体系弓！起人们广泛的兴趣。，方们授有寿比山于PEG链的空间位阴．效应可以避免单核噬菌体的吞噬，、并且可以通过控制可降解部分的降解行为实现药物的持续释放，使在微载体内所包载的药物分子持续释放出来。尽管高聚物的胶束和纳米粒子作为药物的胶体载体已作厂泛研究，但是对其本身物理化学性质与应用之间的联系研究甚少。因此本文对一系列PLLA和PEG两嵌段和三嵌段共聚物的自聚集行为进行了细致研究，得到了以卜结论：1．以花为"模型药物"，通过荧光探针技术对一系列两亲性共聚物在水呀招夜和NaCI溶液种的胶束化行为进行了研究。这些共聚物是由一种新型氨钙催化利，以人分J，的聚乙二醇（PEG）为引发剂，引发丙交酷开环聚合得到，，其中囚定长度阴 PEG段分剐为44，104和113环氧乙烷早兀，PLLA的长没在15-280乳酸中元之间。由于氨钙准活性的特点，这些共聚物的分散度较低，均在1.1-1.3之间。其临界胶束浓度cmc发现随PLLA的含量增加I荆氏。具有同一PEG长度的两嵌段和三嵌段共聚物cmc值的截然差别为它们胶束的构型不同提供了证据。同时也发现了NaCI的加入对丫EG段和争LLA段较短洪聚物的cmc的降低有明掀笋作用，而对具有较长PEG段或较长PLLA段的共聚物的cmc基本上没有什么影响。2．通过荧光探余十技术测定花在这一系列共聚物胶束溶液锄勺配分系数在0.2*10~5至1.9*10~5之间，对于同-PEG段的共聚物，花在其胶柬相中的配分系数随PLLA的含量的增加而增加。另外发现NaCl的加入能够促进花在胶束相中的配分。3．通过透射电子显微镜研究了两嵌段共聚物水溶液胶束的形貌，发现胶束的粒径和分散度均随PLLA段的增加而增加：通过原子力显微镜研究"这些纳米粒子退火前后的形貌变化，发现退火后纳米粒子重新自聚集为类似于神经网络红脚乏的"纳米条带"结构，其中心为类似"神经元"的团簇结构，而周困为支化的车由突"分支结构，这与文献上提到的只有三嵌段共聚物能够形成支化的"纳米条带"结构截然不同，其自聚集机理在进，步研究之中。4．以亲水性的荧光素为荧光探针研究了两嵌段共聚物在甲苯中的胶束化行为，发现其clnc值随PLLA段的含量增加而降低，相对于PEG段，PLLA段在其胶宋化过程中起主要作用。通过1HNMR证明两嵌段共聚物在甲苯中的胶束具伯以PLLA段为"核"、PEG段为"壳"的"核-壳"结构，这种胶柬化行为通过溶解度参数的差异进行了解释。5.通过原子力显微镜发现，当这些胶束滴加在云母表面上经过热处理后，这些胶束重新自聚集成为规则的具有平缓隆起的纳米结构，这与由水中得到的胶柬热处理后的形貌截然不同，并对此进行了进一步解释。由XPS分析认为主要是PEG段覆盖在PLLA段表面。

骨固定用聚乳酸/无机纳米粒子复合材料

本论文针对目前用于骨固定和骨修复的聚乳酸／无机纳米粒子复合材料的界面强度低、粒子分散不均匀以及所采用生物活性无机填料粒径较大等缺点，对轻基磷灰石及生物活性玻璃无机纳米粒子的制备、界面改性、粒子的分散、以及复合材料的制备进行了较详细的论述。另外，对材料的力学性能、结晶性能和生物相容性进行了较细统的测试和研究。（1）以磷酸和氢氧化钙为原料在40-80℃的反应条件下制备出了米粒状和棒状的HAP粒子，然后在-50℃的冷冻干燥机中干燥48h，得到白色的HAP粉末。用TEM、SEM、WAXD、FTIR等对所得产物进行了表征。研究结果表明，提高反应温度有利于生成高结晶度的长棒状HAP颗粒。此外，锻烧温度对粒子的形貌和结晶度也有很大的影响，锻烧温度越高，粒子的结晶度就越高，并且，当锻烧温度提高到900℃以上时，HAP粒子的形貌会由长棒形逐渐变成球形。（2）在高纯氢气气氛中，以辛酸亚锡为催化剂的反应条件下使左旋丙交酷开环聚合，直接接枝到HAP的表面，使HAP的粒子表面覆盖一层聚乳酸分子，使HAP的亲油性能得到提高。对表面接枝的轻基磷灰石（g-HAP）用31PMAS-NMR、FTIR、TGA、TEM、SEM和GPC进行了表征。结果表明，用此方法可在HAP表面接枝6％的PLLA。（3）用溶剂法制备了PLLA/g-HAP复合材料，并对其机械性能、结晶性能和生物相容性进行了表征。试验结果表明：与纯HAP相比，g-HAP粒子更容易均匀分散到PLLA基体中，当填料含量达到4％时，PLLAg-HAP复合材料的力学性能达到最好。由Dsc和PoM的实验结果表明，g-HAP粒子在聚合物基体中可以起到异相成核剂的作用。细胞实验结果表明，PLL刀g-HAP复合材料的细胞相容性明显优于纯的PLLA和PLLA/HAP复合材料。（4）以正硅酸乙酷（TEOS）、硝酸钙（Ca(NO3）2）和磷酸氢二按（（NH4）ZHPO4）为原料，利用在酸性溶液中水解，碱性溶液中缩聚沉淀，然后将反应液离心分离，冷冻干燥，最后在马弗炉中锻烧的方法，得到白色的5102-coo-PZos三元生物活性玻璃粉末。SEM和TEM分析结果表明，所得到生物活性玻璃是粒径在40nln左右的球形颗粒，且粒径分布非常均匀。（5）以正硅酸乙酷（TEoS）和硝酸钙（Ca（NO3）2）为原料，利用在酸性溶液中水解，碱性溶液中缩聚沉淀，然后将反应液离心分离，冷冻干燥，最后在马弗炉中锻烧的方法，得到粒径为200nm左右的球形SiO2-CaO二元生物活性玻璃粉末。

functional monomers and polymers.CXXXVI.effect of metal ions on the interaction of synthetic nucleic acid analogs

The effect of metal ions on the conformation of thymine-containing poly-D-lysine was studied by CD spectra in aqueous solution. Of the metal ions studied,only copper(Ⅱ)ion affected the conformation of mucleic acid analogs .copper(Ⅱ)ion also affected the specifically interacting system made up of thymine-containing poly-D-lysine and polyadenylic acid.