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Biomedical subjects

D Chen

Publications and source records attributed to D Chen.

At least 19 recordsLinked to original sources

Maternal anxiety and ultrasound markers for aneuploidy in a multiethnic population.

OBJECTIVE: Discussion of isolated ultrasound (US) markers for fetal aneuploidy can provoke significant patient anxiety. The objective of this study is to quantify maternal anxiety associated with the detection of these markers. METHODS: All patients undergoing routine second-trimester US examination for fetal anatomical survey over a one-year period were administered the State-Trait Anxiety Inventory (STAI) for Adults before and after the procedure. Women with isolated fetal markers for aneuploidy were notified of the findings but discouraged from pursuing amniocentesis. Rates of normal US examination, aneuploidy markers, anomalies, amniocentesis, and pregnancy outcomes were assessed across the ethnic groups. Pre- and post-ultrasound STAI surveys were scored and standardized with previously established norms. Student t-tests, Chi-square, and analysis of variance (ANOVA) were used where appropriate. RESULTS: Among the 798 patients tested, 57% were Hispanic, 30% were Asian, 6% were Black, and 7% were White. Maternal anxiety level was decreased in women after a normal US. The anxiety level increased with aneuploidy markers and was the highest with anomalies. Aneuploidy markers were more common among Hispanic and Asian fetuses, without any associated aneuploidy. Women with isolated aneuploidy markers underwent amniocentesis as often as women with advanced maternal age. CONCLUSION: The detection and communication of isolated aneuploidy markers is associated with increased maternal anxiety and unnecessary amniocentesis.

Adult↗

Biological activities of a novel selective oestrogen receptor modulator derived from raloxifene (Y134).

BACKGROUND AND PURPOSE: Selective oestrogen receptor (ER) modulators (SERMs) are of great value in the treatment of breast cancer and osteoporosis. The aim of this study was to characterize pharmacologically a new class of SERMs synthesized based on the core structure of raloxifene. EXPERIMENTAL APPROACH: Competitive receptor binding and luciferase-based reporter methods were used to study the bioactivities of raloxifene analogues, followed by efficacy determination in breast cancer cell proliferation assay. ER antagonist effects were investigated in female rats by measuring uterine and mammary gland growth, using wet weight, BrdU incorporation and terminal end bud (TEB) as indicators. KEY RESULTS: Five analogues, belonging to two different structural series and display higher binding affinities for ERalpha than ERbeta were functionally evaluated. One such analogue, Y134, exhibited potent antagonist activity at ERs in CV-1 cells cotransfected with plasmids containing ERalpha or ERbeta and oestrogen-response element-driven luciferase. The estimated IC(50) value was 0.52 nM for ERalpha and 2.94 nM for ERbeta, comparable to that of raloxifene. Little cytotoxicity was observed at Y134 concentrations below 10 microM. Y134 suppressed oestrogen-stimulated proliferation of ER-positive human breast cancer MCF-7 and T47D cells. At an identical dose, administered to ovariectomized rats, Y134 was more effective than raloxifene at arresting oestrogen-induced outgrowth of TEB and mammary gland DNA synthesis, but their inhibitory effects on the uterus were comparable. CONCLUSIONS AND IMPLICATIONS: Y134 is a potent ER antagonist with better mammary gland selectivity than raloxifene and shows potential for development as a new SERM for therapeutic use.

Animals↗

Pol I transcription and pre-rRNA processing are coordinated in a transcription-dependent manner in mammalian cells.

Pre-rRNA synthesis and processing are key steps in ribosome biogenesis. Although recent evidence in yeast suggests that these two processes are coupled, the nature of their association is unclear. In this report, we analyze the coordination between rDNA transcription and pre-rRNA processing in mammalian cells. We found that pol I transcription factor UBF interacts with pre-rRNA processing factors as analyzed by immunoprecipitations, and the association depends on active rRNA synthesis. In addition, injections of plasmids containing the human rDNA promoter and varying lengths of 18S rDNA into HeLa nuclei show that pol I transcription machinery can be recruited to rDNA promoters regardless of the product that is transcribed, whereas subgroups of pre-rRNA processing factors are recruited to plasmids only when specific pre-rRNA fragments are produced. Our observations suggest a model for sequential recruitment of pol I transcription factors and pre-rRNA processing factors to elongating pre-rRNA on an as-needed basis rather than corecruitment to sites of active transcription.

DNA, Ribosomal↗

Enantiomeric free radicals and enzymatic control of stereochemistry in a radical mechanism: the case of lysine 2,3-aminomutases.

The product of yjeK in Escherichia coli is a homologue of lysine 2,3-aminomutase (LAM) from Clostridium subterminale SB4, and both enzymes catalyze the isomerization of (S)- but not (R)-alpha-lysine by radical mechanisms. The turnover number for LAM from E. coli is 5.0 min(-1), 0.1% of the value for clostridial LAM. The reaction of E. coli LAM with (S)-alpha-[3,3,4,4,5,5,6,6-(2)H8]lysine proceeds with a kinetic isotope effect (kH/kD) of 1.4, suggesting that hydrogen transfer is not rate-limiting. The product of the E. coli enzyme is (R)-beta-lysine, the enantiomer of the clostridial product. Beta-lysine-related radicals are observed in the reactions of both enzymes by electron paramagnetic resonance (EPR). The radical in the reaction of clostridial LAM has the (S)-configuration, whereas that in the reaction of E. coli LAM has the (R)-configuration. Moreover, the conformations of the beta-lysine-related radicals at the active sites of E. coli and clostridial LAM are different. The nuclear hyperfine splitting between the C3 hydrogen and the unpaired electron at C2 shows the dihedral angle to be 6 degrees, unlike the value of 77 degrees reported for the analogous radical bound to the clostridial enzyme. Reaction of (S)-4-thialysine produces a substrate-related radical in the steady state of E. coli LAM, as in the action of the clostridial enzyme. While (S)-beta-lysine is not a substrate for E. coli LAM, it undergoes hydrogen abstraction to form an (S)-beta-lysine-related radical with the same stereochemistry of hydrogen transfer from C2 of (S)-beta-lysine to the 5'-deoxyadenosyl radical as in the action of the clostridial enzyme. The resulting beta-lysyl radical has a conformation different from that at the active site of clostridial LAM. All evidence indicates that the opposite stereochemistry displayed by E. coli LAM is determined by the conformation of the lysine side chain in the active site. Stereochemical models for the actions of LAM from C. subterminale and E. coli are presented.

Bacterial Proteins↗

Anisotropy and corotation of galactic cosmic rays.

The intensity of Galactic cosmic rays is nearly isotropic because of the influence of magnetic fields in the Milky Way. Here, we present two-dimensional high-precision anisotropy measurement for energies from a few to several hundred teraelectronvolts (TeV), using the large data sample of the Tibet Air Shower Arrays. Besides revealing finer details of the known anisotropies, a new component of Galactic cosmic ray anisotropy in sidereal time is uncovered around the Cygnus region direction. For cosmic-ray energies up to a few hundred TeV, all components of anisotropies fade away, showing a corotation of Galactic cosmic rays with the local Galactic magnetic environment. These results have broad implications for a comprehensive understanding of cosmic rays, supernovae, magnetic fields, and heliospheric and Galactic dynamic environments.

Journal Article↗

Postinjury vascular intimal hyperplasia in mice is completely inhibited by CD34+ bone marrow-derived progenitor cells expressing membrane-tethered anticoagulant fusion proteins.

BACKGROUND: Coagulation proteins promote neointimal hyperplasia and vascular remodelling after vessel injury, but the precise mechanisms by which they act in vivo remain undetermined. OBJECTIVES: This study, using an injury model in which the neointima is derived from bone marrow (BM)-derived cells, compared inhibition of tissue factor or thrombin on either BM-derived or existing vascular smooth muscle cells. METHODS: Two transgenic (Tg) mouse strains expressing membrane-tethered tissue factor pathway inhibitor (TFPI) or hirudin (Hir) fusion proteins driven by an alpha smooth muscle actin (SMA) promoter were generated (alpha-TFPI-Tg and alpha-Hir-Tg) and the phenotype after wire-induced endovascular injury was compared with that in wild-type (WT) controls. RESULTS: WT mice developed progressive neointimal expansion, whereas injury in either Tg was followed by repair back to a preinjured state. This was also seen when WT mice were reconstituted with BM from Tg mice but not when Tgs were reconstituted with WT BM, in which injury was followed by slowly progressive neointimal expansion. Injection of CD34+ cells from Tg mice into injured WT mice resulted in the accumulation of fusion protein-expressing cells from day 3 onwards and an absence of neointimal hyperplasia in those areas. CONCLUSIONS: Neointimal development after wire-induced endovascular injury in mice was completely inhibited when BM-derived cells infiltrating the damaged artery expressed membrane tethered anticoagulant fusion proteins under an alpha-SMA promoter. These findings enhance our understanding of the pathological role that coagulation proteins play in vascular inflammation.

Animals↗

ARF-BP1 as a potential therapeutic target.

In this review, we discuss the recent identification of ARF-BP1 (also known as Mule, UREB1, E3(histone), LASU1, and HectH9). ARF-BP1, a HECT domain-containing E3 ubiquitin ligase, interacts with ARF and p53. Its ubiquitin ligase activity is inhibited by ARF. Inactivation of ARF-BP1 stabilised p53 and induced apoptosis. Notably, inactivation of ARF-BP1 also caused cell growth repression in p53-null cells and breast cancer cells with mutant p53. Thus, ARF-BP1 emerges as a novel therapeutic target against cancer regardless of p53 status.

Cell Division↗

The ratio of circulating osteoprotegerin to RANKL in early rheumatoid arthritis predicts later joint destruction.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease that may result in debilitating joint deformities with destruction of bone and cartilage. Inflammation is still considered the pivotal inducer of both components of joint damage. Results of recent animal studies suggested a prominent contribution of osteoclastic bone resorption that could be dissociated from inflammation. RANKL and its natural decoy receptor, osteoprotegerin (OPG), play key roles in osteoclast activation. In a group of patients with early RA not treated with disease-modifying drugs, we tested the hypothesis that osteoclast activation, reflected by the serum OPG:RANKL ratio at baseline, is negatively associated with progression of bone damage, independent of inflammation. METHODS: OPG and RANKL levels, together with a parameter of inflammation (first-year time-averaged erythrocyte sedimentation rate [tESR]), were measured in 92 patients with newly diagnosed early active RA who were participants in a randomized study. The tESR and the OPG:RANKL ratio were evaluated for the ability to predict 5-year radiographic progression of joint damage. RESULTS: The first-year tESR and the OPG:RANKL ratio, as measured at baseline, independently predicted 5-year radiographic progression of joint damage (both P < or = 0.001). Progression of radiographic damage was greatest in patients with a high tESR and a low OPG:RANKL ratio and was lowest in patients with a low tESR and a high OPG:RANKL ratio. CONCLUSION: This study in patients with early untreated RA is the first to confirm the findings in animal models of arthritis, that radiographic progression of the bone component of joint destruction is dependent on both inflammation (tESR) and osteoclast activation (the OPG:RANKL ratio).

Arthritis, Rheumatoid↗

Induction of accommodation model by combined RNA interference targeting 1,3-galactosyltransferase gene and low-dose GS-IB4 lectin in vitro.

OBJECTIVE: This study sought to mimic the interaction of xenograft endothelial cells and human serum in vitro after successfully silencing the expression of porcine alpha1,3-galactosyltransferase (alpha1,3GT) gene by RNA interference (RNAi), and to investigate the possibility of inducing accommodation in vitro by stimulation of alpha-Gal-specific binding lectin, Griffonia simplicifolia isolectin B4 (GS-IB4) and RNAi. MATERIALS AND METHODS: Various alpha-Gal expression patterns on a pig endothelial cell immortalized line (PED) was achieved by serial doses of small interfering RNA (siRNA) targeting porcinc alpha1,3GT gene. alpha1,3GT-siRNA transfected PEDs were exposed to increasing doses of GS-IB4 lectin (0.5, 2, and 8 microg/mL) for 4 hours before incubation with normal human serum (NHS). Accommodation phenomenon of PEDs in NHS was observed by 51Cr release and antibody/complement binding assays. RESULTS: With combined RNAi and low-dose GS-IB4 stimulation, PEDs remarkably inhibited complement-mediated cytotoxicity, which showed a better protective effect than using RNAi alone. At a concentration of 2 mug/mL, GS-IB4 exhibited the maximum protective effect. The expression of E-selectin on alpha1,3GT-siRNA transfected PEDs did not differ from that on parental PEDs with heat-inactivated NHS (HINHS) stimulation. Combined with GS-IB4 stimulation, however, it inhibited expression of E-selectin, which was GS-IB4 dose dependent, resulting in mean fluorescence intensity values of 98.5, 42.0, and 36.3 at 0.5, 2, and 8 microg/mL. The mRNA expression of the protective gene HO-1 was significantly up-regulated after treatment with RNAi and low-dose of GS-IB4. CONCLUSIONS: Combined RNAi and low-dose GS-IB4 induced pig endothelial cell accommodation in vitro. The level of alpha-Gal expression played an important role in the induction of accommodation.

Animals↗

Employment of liver tissue slice analysis to assay hepatotoxicity linked to replicative and nonreplicative adenoviral agents.

Whereas virotherapy has emerged as a novel and promising approach for neoplastic diseases, appropriate model systems have hampered preclinical evaluation of candidate conditionally replicative adenovirus agents (CRAds) with respect to liver toxicity. This is due to the inability of human viral agents to cross species. We have recently shown the human liver tissue slice model to be a facile means to validate adenoviral replication. On this basis, we sought to determine whether our ex vivo liver tissue slice model could be used to assess CRAd-mediated liver toxicity. We analyzed and compared the toxicity of a conditionally replicative adenovirus (AdDelta24) to that of a replication incompetent adenovirus (Adnull [E1-]) in mouse and human liver tissue slices. To accomplish this, we examined the hepatic apoptosis expression profile by DNA microarray analyses, and compared these results to extracellular release of aminotransferase enzymes, along with direct evidence of apoptosis by caspase-3 immunhistochemical staining and TUNEL assays. Human and mouse liver tissue slices demonstrated a marked increase in extracellular release of aminotransferase enzymes on infection with AdDelta24 compared to Adnull. AdDelta24-mediated liver toxicity was further demonstrated by apoptosis induction, as detected by caspase-3 immunohistochemical staining, TUNEL assay and microarray analysis. In conclusion, concordance of CRAd-mediated apoptosis in both the human and the mouse liver tissue slice models was demonstrated, despite the limited replication ability of CRAds in mouse liver slices. The results of this study, defining the CRAd-mediated apoptosis gene expression profiles in human and mouse liver, may lay a foundation for preclinical liver toxicity analysis of CRAd agents.

Adenoviridae↗

Allelic distribution of HLA class I genes in the Tibetan ethnic population of China.

Tibetans live in Qinghai-Tibet Plateau rising about 4000 m a.s.l. in south-west China. Archaeological evidences suggested that there have been humans living in Tibet at least 5000 years ago. However, Tibetan earlier history remains elusive. In the present study, allelic distribution of human leucocyte antigen (HLA)-A, -B and -Cw in 158 unrelated Tibetan Chinese was investigated using sequencing-based typing methods, and a total of 25 HLA-A, 45 HLA-B and 20 HLA-Cw alleles were identified. A*24G1 (27.2%), B*51G1 (16.8%), Cw*04G1 (13.3%) and Cw*070201G1 (13.3%) are the most common HLA-A, -B and -Cw alleles. The most frequently detected haplotypes were A*24G1-B*51G1-Cw*140201 (3.6%), A*24G1-B*51G1 (6.8%), A*02G1-Cw*070201G1 (6.5%) and B*51G1-Cw*140201 (5.0%). Chi-squared test suggested that all three loci fitted the Hardy-Weinberg expectations. No evidence for a departure from selective neutrality at the HLA-A and -B loci was observed. However, significant departure of the observed homozygosity from the expected values was found for HLA-Cw. Though the contemporary Tibetans inhabit the south-west China, Nei's genetic distance measure based on frequencies of HLA-A, -B and -Cw indicated that Tibetans were closer to northern Han Chinese, Mongolian Chinese, Koreans and Japanese rather than to southern Han Chinese. The corresponding dendrogram constructed according to the neighbour-joining method supported that Tibetans separated from southern Han and located in North-East Asian cluster which included northern Han Chinese and Mongolian Chinese. These data were in good agreement with language classification and with a recent hypothesis that Tibetan might originate from northern China along Yellow river.

Alleles↗

ECL cell histamine mobilization and parietal cell stimulation in the rat stomach studied by microdialysis and electron microscopy.

AIM: Gastrin stimulates acid secretion by mobilizing histamine from enterochromaffin-like (ECL) cells that occur predominantly at the base of the gastric glands. The parietal cells occur higher up in the glands nearer to the gastric lumen. The present study was performed to assess whether histamine is transported from the ECL cell via the microcirculation (endocrine route) or local diffusion (paracrine route). METHODS: Totally isolated, vascularly perfused, rat stomachs were examined both in basal and gastrin-stimulated state. Histamine concentrations, determined by radioimmunoassay in venous effluent and microdialysate from an indwelling probe in the submucosa, were monitored over a period of 240 min. Gastrin-17 was infused through an arterial catheter for 120 min. The parietal cells were examined by electron microscopy, and the percentage of actively secreting parietal cells (displaying secretory canaliculi) in four regions along the glands (basal to surface, zones I-IV) was determined. RESULTS: Gastrin stimulated acid secretion and histamine release as well as parietal cell activation. Upon gastrin stimulation, histamine concentration in the microdialysate was 2.5-fold higher than in the venous effluent (P = 0.008). The parietal cells in the upper part of the gland (zone III) were found to be activated the most. CONCLUSION: As the histamine concentrations were higher in the tissue (microdialysate) than in blood, histamine seems to reach the parietal cells via the paracrine route. The fraction of active parietal cells seems to depend more on the age of the parietal cells than on the distance from the ECL cell.

Animals↗

Cell-matrix talks: effects on differentiation of hepatocellular carcinoma.

Different event is a process that is dependent on stimulation of extracellular signals, signal transduction and gene express. Malignant transformation of hepatocytes may occur in cirrhosis, which is the result of extracellular matrix (ECM) remodeling. ECM could affect and maintain the differentiated phenotype of hepatocytes by regulating liver transcription factors. Moreover, ECM remodeling is correlated with dedifferentiation of hepatocellular carcinoma (HCC). Integrin-matrix adhesion system and E-cadherin/catenin adhesion complex mediate the cell-matrix interaction through focal adhesion kinase, extracellular-signal-regulated kinases and beta catenin/Wnt pathway. The different event of HCC compared with the reversion of abnormal cell-matrix interaction. New drugs that are power for regulating cell-matrix interaction may represent a novel therapeutic strategy for HCC.

Cadherins↗

Psychological symptoms and nonfatal unintentional injuries among Chinese adolescents: a prospective study.

PURPOSE: To describe patterns of nonfatal unintentional injuries and investigate the association of psychological symptoms with injury risk among adolescents in Guangxi, China. METHODS: Adolescents were selected from middle and high school students in Baise City, Guangxi, China. Psychological symptoms at baseline were measured using SCL-90-R and nonfatal unintentional injuries that occurred among participants were recorded using a standardized injury surveillance questionnaire. Annual injury rates per 100 adolescents by adolescents' demographic and family characteristics were calculated. Student's t-test and the Chi-square test were used to test differences in mean raw scores of SCL-90-R subscales and injury rates. Relative risks and odds ratios of injury with 95% confidence intervals were calculated in univariate analyses and multivariate logistic models. RESULTS: A total of 1474 middle and high school students finished the study. Of them, 442 reported nonfatal unintentional injuries during the study period, resulting in an annual injury rate of 30.3 per 100 adolescents. Boys had a significantly higher injury rate than girls (32.6% vs. 27.4%). Injury rate decreased as the adolescents' age increased. Compared with adolescents who were not injured, the injured adolescents had higher average raw scores of all subscales of SCL-90-R, with an exception of the subscale for hostility. All SCL-90-R subscales factors, except those for hostility and phobia, were associated with injury risk. After confounding effects of age, gender, and ethnicity were controlled using logistic regression models, SCL-90-R subscales for somatization (OR = 2.00, 95% CI 1.52-2.63), obsessive-compulsiveness (OR = 2.10, 95% CI 1.71-2.58), interpersonal-sensitivity (OR = 1.66, 95% CI 1.34-2.06), depression (OR = 2.00, 95% CI 1.59-2.51), anxiety (OR = 2.08, 95% CI 1.62-2.66), and psychoticism (OR = 1.60, 95% CI 1.26-2.03) were significantly associated with an elevated injury risk. CONCLUSION: Psychological symptoms are associated with an elevated risk of nonfatal unintentional injury among middle and high school students. Mental health services, such as psychological counseling, may help reduce the risk of nonfatal unintentional injuries among Chinese adolescents.

Accidents↗

Apoptosis-stimulating protein of p53-2 (ASPP2/53BP2L) is an E2F target gene.

The p53 pathway is a central apoptotic regulator. Deregulation of the Rb/E2F pathway occurs in a majority of tumors, resulting in both unrestrained proliferation and enhanced apoptosis sensitivity via p53-dependent and independent mechanisms. However, the mechanisms coupling the p53 and Rb/E2F pathways remain incompletely understood. We report that ASPP2/53BP2L, a p53/p73-binding protein that promotes p53/p73-dependent apoptosis, is an E2F target gene. The ASPP2/53BP2L promoter was identified and ectopic expression of transcription-competent E2F-1 (E2F-2 and E2F-3) stimulated an ASPP2/53BP2L promoter-luciferase reporter. Mutational analysis of the ASPP2/53BP2L promoter identified E2F-binding sites that cooperate for E2F-1 induction and basal repression of ASPP2/53BP2L. Moreover, endogenous ASPP2/53BP2L levels increased after E2F-1 expression, and E2F-1 bound the endogenous ASPP2/53BP2L promoter after chromatin immunoprecipitation. Typical for an E2F target, ASPP2/53BP2L expression was maximal in early S-phase. Thus, ASPP2/53BP2L is downstream of E2F, suggesting that it functions as a common link between the p53/p73 and Rb/E2F apoptotic pathways.

Apoptosis↗

Preparation of bovine serum albumin loaded poly (D, L-lactic-co-glycolic acid) microspheres by a modified phase separation technique.

BSA-loaded mcirospheres were prepared by a modified phase separation method, in which petroleum ether (PE) containing a certain amount of Span 80 rather than poly (dimethylsiloxane) (PDMS) was adopted as coacervating agent. Process parameters such as Span 80 concentration, the volume and addition rate of coacervating agent, polymer concentration, agitation rate during the phase separation process and PE type were evaluated to optimize the protein encapsulation. It was found microspheres with high yield (>80.0%) and entrapment efficiency (>90%) could be obtained using PE containing 5.0% Span 80 as the coacervating agent. Microspheres with small particle size (<10 microm) could be produced successfully with appropriate process parameters. In vitro release study suggested that burst release was significantly influenced by Span 80 concentration, polymer concentration and PE type and the burst release could be reduced to <20% with optimized formulation. A biphasic release behavior in vitro test was observed for the microspheres prepared by this method. GC analysis demonstrated that residual solvent of DCM and petroleum ether was decreased dramatically in comparison with PDMS used as a conventional coacervating agent.

Alkanes↗

Optimizing double emulsion process to decrease the burst release of protein from biodegradable polymer microspheres.

The process parameters such as the compositions of inner and outer aqueous phase and emulsification technique of the primary emulsion were optimized to decrease the burst release of BSA from biodegradable polymer microspheres in double emulsion method. It was found that diminished burst release of -14% was achieved for the microspheres produced by formulations, where no phosphate was present in the inner water phase (non-buffered system). Primary emulsion made by probe sonication rather than homogenization or mechanical stirring led to microspheres with insignificant burst effect. Microspheres obtained using 0.1% aqueous Tween 80 solution as the outer aqueous phase, frequently exhibit reduced burst effect of 2.7%. Low microsphere yield (52.1%), however, was observed. Microsphere yield was, therefore, enhanced by addition of additive such as sodium chloride, glucose or mannitol into the outer aqueous phase. Decrease in BSA entrapment was observed in the presence of sodium chloride, but reduction in entrapment efficiency was observed in the case of glucose. Burst release increased from 2.7% to 9.5% or 3.4% as 2.5% sodium chloride or 7.5% glucose was added into the outer aqueous phase respectively. Marked burst release (>20%) was observed in the presence of additive of higher concentration independent of sodium chloride or glucose. As far as surfactant type was concerned, diminished burst was found when PVP or Tween 80 rather than PVA was utilized as the surfactant during microsphere preparation. In addition to PLGA, the copolymers of L-lactide (LLA) and dimethyl trimethylene carbonate (DTC) or trimethylene carbonate (TMC) were also evaluated. Insignificant burst effect was found for the microspheres composed of DTC or TMC copolymers.

Animals↗