A20 inhibits periodontal bone resorption and NLRP3-mediated M1 macrophage polarization.

A20 is involved in inflammation and bone metabolism in periodontitis. Regulation of macrophage polarization may be an effective target for periodontitis treatment, and A20 has a regulatory role in macrophage polarization. This study aimed to explore the effects of A20 on macrophage polarization in periodontitis and the underlying mechanism. Adeno-associated virus (AAV) targeting A20 was exploited to achieve A20 knockdown or overexpression in periodontal tissues of mice with experimental periodontitis. The (AAV-A20-RNAi) +P group showed increased alveolar bone resorption when compared with PBS + P and CON305 + P groups. However, the degree of bone destruction was reduced in the (AAV-A20) +P group relative to PBS + P and CON299 + P groups. A20 knockdown resulted in enhanced inducible nitric oxide synthase (iNOS) expression and decreased CD206 expression in mice periodontal tissues. In addition, higher levels of M1 macrophage polarization markers (iNOS, CD86, TNF-α) and lower CD206 expression were found in THP-1 cells treated with lipopolysaccharide (LPS) from Porphyromonas gingivalis (P. gingivalis) (Pg. LPS) and interferon-γ (IFN-γ) when A20 was silenced. A20 overexpression showed opposite effects on macrophage polarization in vivo and in vitro. Knockdown of A20 was correlated with upregulation of the NLRP3 inflammasome pathway in mice periodontal tissues or THP-1 cells. On the contrary, A20 overexpression inhibited the NLRP3 inflammasome pathway. MCC950 suppressed M1 macrophage polarization aggravated through A20 knockdown in Pg. LPS and IFN-γ stimulated cells. Our data suggested that A20 inhibits periodontal bone resorption and NLRP3-mediated M1 macrophage polarization; A20 is expected to be a novel target for the treatment of periodontitis.

A rare case of pemphigus vulgaris disguised as a malignant gingival ulcer.

BACKGROUND: Pemphigus vulgaris (PV) is a kind of rare and severe autoimmune bullous disease. In this case, the specificity of oral PV lies in the clinical manifestations of a single palatal ulcer, and no blisters were found in the oral mucosa. This case provides a powerful reference for dentists diagnosing and treating oral PV with atypical clinical presentations. CASE PRESENTATION: A 54 years old female patient presented with a non-healing palatal gingival ulcer for over three months. By histopathological H&E staining and the direct immunofluorescence (DIF) test, the final diagnosis was oral PV. After topical glucocorticoid therapy, the affected area was cured. CONCLUSIONS: In patients with prolonged erosion of the skin or oral mucosa, even if complete blisters are not visible, the physician should consider autoimmune bullous diseases and pay attention to avoid diagnostic defects.

Development and optimization of levodopa and benzylhydrazine orally disintegrating tablets by direct compression and response surface methodology.

The number of Parkinson's disease (PD) patients with the advanced phase and motor fluctuations is increasing. The objective of this study is developing levodopa/benzylhydrazine orally disintegrating tablets (L/B ODTs), which would provide greater convenience and ease of use than conventional tablets for these patients. In the present study, the L/B ODTs were developed successfully with an optimized formulation using response surface methodology (RSM). The direct compression technology was employed for the preparation of L/B ODTs. Considerably shorter disintegration time and faster dissolution profile were obtained under the optimum formulation with microcrystalline cellulose 25.7%, cross-polyvinylpyrrolidone 6.22% and Sodium carboxymethyl starch 5.36%. The content uniformity (%) of levodopa and benzylhydrazine was 50 ± 1.4% and 14.25 ± 0.6%, respectively. Thickness, friability, hardness and wetting time were 2.8 ± 0.05 mm, 0.46 ± 0.21%, 5.42 ± 1.1 kp and 31.2 ± 2.1 s, respectively, and all of data well comply with the General Principles of the Chinese Pharmacopeia. Mannitol of 22% in formulation could bring a pleasant taste: sweet, cool and refreshing. Almost all the volunteers felt that the ODTs had good taste, no roughness, and no gritty feeling, indicating that the ODTs prepared had good palatability, so patients will have good compliance when taking medicine.

Role of Acetyltransferase PG1842 in Gingipain Biogenesis in Porphyromonas gingivalis.

Porphyromonas gingivalis, the major etiologic agent in adult periodontitis, produces large amounts of proteases that are important for its survival and pathogenesis. The activation/maturation of gingipains, the major proteases, in P. gingivalis involves a complex network of processes which are not yet fully understood. VimA, a putative acetyltransferase and virulence-modulating protein in P. gingivalis, is known to be involved in gingipain biogenesis. P. gingivalis FLL92, a vimA-defective isogenic mutant (vimA::ermF-ermAM) showed late-onset gingipain activity at stationary phase, indicating the likelihood of a complementary functional VimA homolog in that growth phase. This study aimed to identify a functional homolog(s) that may activate the gingipains in the absence of VimA at stationary phase. A bioinformatics analysis showed five putative GCN5-related N-acetyltransferases (GNAT) encoded in the P. gingivalis genome that are structurally related to VimA. Allelic exchange mutagenesis was used to make deletion mutants for these acetyltransferases in the P. gingivalisvimA-defective mutant FLL102 (ΔvimA::ermF) genetic background. One of the mutants, designated P. gingivalis FLL126 (ΔvimA-ΔPG1842), did not show any late-onset gingipain activity at stationary phase compared to that of the parent strain P. gingivalis FLL102. A Western blot analysis of stationary-phase extracellular fractions with antigingipain antibodies showed immunoreactive bands that were similar in size to those for the progingipain species present only in the ΔvimA-ΔPG1842 isogenic mutant. Both recombinant VimA and PG1842 proteins acetylated Y230, K247, and K248 residues in the pro-RgpB substrate. Collectively, these findings indicate that PG1842 may play a significant role in the activation/maturation of gingipains in P. gingivalisIMPORTANCE Gingipain proteases are key virulence factors secreted by Porphyromonas gingivalis that cause periodontal tissue damage and the degradation of the host immune system proteins. Gingipains are translated as an inactive zymogen to restrict intracellular proteolytic activity before secretion. Posttranslational processing converts the inactive proenzyme to a catalytically active protease. Gingipain biogenesis, including its secretion and activation, is a complex process which is still not fully understood. One recent study identified acetylated lysine residues in the three gingipains RgpA, RgpB, and Kgp, thus indicating a role for acetylation in gingipain biogenesis. Here, we show that the acetyltransferases VimA and PG1842 can acetylate the pro-RgpB gingipain species. These findings further indicate that acetylation is a potential mechanism in the gingipain activation/maturation pathway in P. gingivalis.

Improvement in early detection of orofacial clefts using the axial view of the maxilla.

OBJECTIVES: To evaluate the performance of the maxilla in the axial view in detection of orofacial clefts (OC) compared with the retronasal triangle (RNT) in the coronal view and palatine line in the sagittal view at the early stage of gestation. METHODS: A total of 2982 fetuses (including 315 twins) were enrolled for the first-trimester screening in this prospective study. The maxilla in the axial view, palatine line in the sagittal view, and RNT in the coronal view were scanned by 2-dimensional ultrasound. RESULTS: Excluded 103 cases lost to follow-up, 2879 fetuses were analyzed in our study. Obtaining rates of the satisfactory image of the maxilla in the axial view, RNT in the coronal view, and palatine line in the sagittal view were 95.2%, 93.8%, and 98.2% respectively. Abnormal axial view of the maxilla, coronal view of the RNT, and sagittal view of the palatine line were observed in 100% (8/8), 75% (6/8), and 50% (4/8) of the CLP cases respectively. CONCLUSIONS: The study demonstrates that using the axial view of maxilla in the diagnosis of OC is feasible and improved the detection of OC compared with the sagittal view of the palatine line and coronal view of the RNT in the first trimester.

Electrochemical sensor based on molecularly imprinted polymer for sensitive and selective determination of metronidazole via two different approaches.

A molecularly imprinted polymer decorated glassy carbon electrode (MIP/GCE) is facilely developed into an electrochemical sensing platform for detection of metronidazole (MNZ). MIP preparation was carried out via in situ electropolymerization and o-phenylenediamine was selected as the optimal functional monomer. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were employed to characterize and assess the performance of the so-obtained sensor. In particular, two assay methods, which are based on different principles, were involved in the detection procedure. One is based on MIP/catalysis (Method І) and the other is MIP/gate effect (Method II). Comparison of these two methods was made in the aspects including detection range, sensitivity, accuracy, selectivity, repeatability, and long-term stability. It is found that Method І affords a lower detection limit of 3.33 × 10(-10) M (S/N = 3) while the detection limit of Method II is 6.67 × 10(-10) M (S/N = 3). The linear range of Method І and II is 1.0 × 10(-9) to 1.0 × 10(-8) M and 2.0 × 10(-9) to 1.0 × 10(-7) M, respectively. The MIP/GCE exhibits good recognition ability towards the template molecule-MNZ in the presence of the analogues of MNZ and other interferents, which can be ascribed to the successful imprinting effect during MIP membrane preparation. Graphical Abstract Procedure for fabricating MIP/GCE and its application in detecting metronidazole in serum.

Volume phase transition mechanism of poly[oligo(ethylene glycol)methacrylate] based thermo-responsive microgels with poly(ionic liquid) cross-linkers.

Thermo-dynamic volume phase transition mechanisms of poly[oligo(ethylene glycol)methacrylate] (POEGMA) based microgels with poly(ionic liquid) (PIL) cross-linking moieties are investigated in detail on the basis of temperature-dependent Fourier transform infrared (FTIR) spectroscopy. The original FTIR data are further analysed by two-dimensional correlation spectroscopy (2Dcos) with the perturbation correlation moving window (PCMW) technique. It is observed that the content of hydrophilic PIL cross-linking structure strongly affects the temperature induced volume phase transition mechanism of microgels in which the less cross-linked microgel exhibits a sharp volume phase transition process while the highly cross-linked microgel presents a broad transition behavior. Peculiarly, the dehydration of C-H groups acts as the driving force for the whole phase transition process within the less cross-linked microgel network and cooperative response of chemical groups is identified. It is deduced that the hydrophilic PIL moieties develop polymer-water-polymer interactions with C=O groups as C=O···D2O-PIL hydrogen bonds emerge in the less cross-linked system. As regards the highly cross-linked microgel system, the phase transition process is driven by the disruption of hydrogen bonds between C=O groups and water molecules while the response of C-H groups becomes insensitive. PIL moieties passively dehydrate following the dehydration of C-H groups on oligo(ethylene glycol) side chains and no hydrogen bond between C=O group and IL-D2O association appears during the phase transition process.

Synthesis of metronidazole-imprinted molecularly imprinted polymers by distillation precipitation polymerization and their use as a solid-phase adsorbent and chromatographic filler.

Metronidazole-imprinted polymers with superior recognition properties were prepared by a novel strategy called distillation-precipitation polymerization. The as-obtained polymers were characterized by Fourier-transform infrared spectroscopy, laser particle size determination and scanning electron microscopy, and their binding performances were evaluated in detail by static, kinetic and dynamic rebinding tests, and Scatchard analysis. The results showed that when the fraction of the monomers was 5 vol% in the whole reaction system, the prepared polymers afforded good morphology, monodispersity, and high adsorption capacity and excellent selectivity to the target molecule, metronidazole. The optimal binding performance is 12.41 mg/g for metronidazole just before leakage occurred and 38.51 mg/g at saturation in dynamic rebinding tests. Metronidazole-imprinted polymers were further applied as packing agents in solid-phase extraction and as chromatographic filler, both of which served for the detection of metronidazole in fish tissue. The results illustrated the recoveries of spiked samples ranged from 82.97 to 87.83% by using molecularly imprinted solid-phase extraction combined with a C18 commercial column and 93.7 to 101.2% by directly using the polymer-packed chromatographic column. The relative standard deviation of both methods was less than 6%.

Preparation and characterization of erythromycin molecularly imprinted polymers based on distillation-precipitation polymerization.

Erythromycin-imprinted polymers with excellent recognition properties were prepared by an innovative strategy called distillation-precipitation polymerization. The interaction between erythromycin and methacrylic acid was studied by ultraviolet absorption spectroscopy, and the as-prepared materials were characterized by Fourier-transform infrared spectroscopy and scanning electron microscopy. Moreover, their binding performances were evaluated in detail by static, kinetic and selective sorption tests. It was found that the molecularly imprinted polymers afforded good morphology, monodispersity, and high adsorption capacity when the fraction of the monomers was 7 vol% in the whole reaction system, and the adsorption data for imprinted polymers correlated well with the Langmuir model. The maximum capacity of the imprinted and the non-imprinted polymers for adsorbing erythromycin is 44.03 and 19.95 mg/g, respectively. The kinetic studies revealed that the adsorption process fitted a pseudo-second-order kinetic model. Furthermore, the imprinted polymers display higher affinity toward erythromycin, compared with its analogue roxithromycin.

Highly Drug-Loaded Nanoaggregate Microparticles for Pulmonary Delivery of Cyclosporin A.

Introduction: Nanoparticles have the advantages of improving the solubility of poorly water-soluble drugs, facilitating the drug across biological barriers, and reducing macrophage phagocytosis in pulmonary drug delivery. However, nanoparticles have a small aerodynamic particle size, which makes it difficult to achieve optimal deposition when delivered directly to the lungs. Therefore, delivering nanoparticles to the lungs effectively has become a popular research topic. Methods: Nanoaggregate microparticles were used as a pulmonary drug delivery strategy for the improvement of the bioavailability of cyclosporine A (CsA). The nanoaggregate microparticles were prepared with polyvinyl pyrrolidone (PVP) as the excipient by combining the anti-solvent method and spray drying process. The physicochemical properties, aerodynamic properties, in vivo pharmacokinetics and inhalation toxicity of nanoaggregate microparticles were systematically evaluated. Results: The optimal nanoparticles exhibited mainly spherical shapes with the particle size and zeta potential of 180.52 nm and -19.8 mV. The nanoaggregate microparticles exhibited irregular shapes with the particle sizes of less than 1.6 µm and drug loading (DL) values higher than 70%. Formulation NM-2 as the optimal nanoaggregate microparticles was suitable for pulmonary drug delivery and probably deposited in the bronchiole and alveolar region, with FPF and MMAD values of 89.62% and 1.74 µm. In addition, inhaled NM-2 had C max and AUC0-∞ values approximately 1.7-fold and 1.8-fold higher than oral cyclosporine soft capsules (Neoral®). The inhalation toxicity study suggested that pulmonary delivery of NM-2 did not result in lung function damage, inflammatory responses, or tissue lesions. Conclusion: The novel nanoaggregate microparticles for pulmonary drug delivery could effectively enhance the relative bioavailability of CsA and had great potential for clinical application.

Assessing airflow unsteadiness in the human respiratory tract under different expiration conditions.

To enhance the understanding of airflow characteristics in the human respiratory system, the expiratory airflow in a human respiratory tract model was simulated using large eddy simulation and dynamic mesh under different expiration conditions aligned with clinically measured data. The airflow unsteadiness was quantitatively assessed using power spectral density (PSD) and spectral entropy (SE). The following findings were obtained: (1) The airflow is highly turbulent in the mouth-pharynx region during expiration, with its dynamic characteristics being influenced by both the transient expiration flow pattern at mouth piece and the glottis motion. (2) PSD analysis reveals that the expiratory airflow is very unsteady, exhibiting a broad-band attenuation spectrum in the pharynx-trachea region. When only transient expiration or glottis motion is considered, the PSD spectrum changes slightly. When both are ignored, however, the change is significant, with the peak frequency reduced to 10% of the real expiration condition. (3) SE analysis indicates that the airflow transitions into turbulence in the trachea, and there may be multiple transitions in the region of soft palate. The transient expiration or glottis motion alone increases turbulence intensity by 2%-15%, while ignoring both reduces turbulence intensity by 10%-20%. This study implies that turbulence characteristics can be significantly different under different expiratory conditions, and therefore it is necessary to determine the expiratory flow characteristics using clinically measured expiratory data.

A new dental CBCT metal artifact reduction method based on a dual-domain processing framework.

Objective.Cone beam computed tomography (CBCT) has been wildly used in clinical treatment of dental diseases. However, patients often have metallic implants in mouth, which will lead to severe metal artifacts in the reconstructed images. To reduce metal artifacts in dental CBCT images, which have a larger amount of data and a limited field of view compared to computed tomography images, a new dental CBCT metal artifact reduction method based on a projection correction and a convolutional neural network (CNN) based image post-processing model is proposed in this paper. Approach.The proposed method consists of three stages: (1) volume reconstruction and metal segmentation in the image domain, using the forward projection to get the metal masks in the projection domain; (2) linear interpolation in the projection domain and reconstruction to build a linear interpolation (LI) corrected volume; (3) take the LI corrected volume as prior and perform the prior based beam hardening correction in the projection domain, and (4) combine the constructed projection corrected volume and LI-volume slice-by-slice in the image domain by two concatenated U-Net based models (CNN1 and CNN2). Simulated and clinical dental CBCT cases are used to evaluate the proposed method. The normalized root means square difference (NRMSD) and the structural similarity index (SSIM) are used for the quantitative evaluation of the method.Main results.The proposed method outperforms the frequency domain fusion method (FS-MAR) and a state-of-art CNN based method on the simulated dataset and yields the best NRMSD and SSIM of 4.0196 and 0.9924, respectively. Visual results on both simulated and clinical images also illustrate that the proposed method can effectively reduce metal artifacts.Significance. This study demonstrated that the proposed dual-domain processing framework is suitable for metal artifact reduction in dental CBCT images.

The emergence of modern zoogeographic regions in Asia examined through climate-dental trait association patterns.

The complex and contrasted distribution of terrestrial biota in Asia has been linked to active tectonics and dramatic climatic changes during the Neogene. However, the timings of the emergence of these distributional patterns and the underlying climatic and tectonic mechanisms remain disputed. Here, we apply a computational data analysis technique, called redescription mining, to track these spatiotemporal phenomena by studying the associations between the prevailing herbivore dental traits of mammalian communities and climatic conditions during the Neogene. Our results indicate that the modern latitudinal zoogeographic division emerged after the Middle Miocene climatic transition, and that the modern monsoonal zoogeographic pattern emerged during the late Late Miocene. Furthermore, the presence of a montane forest biodiversity hotspot in the Hengduan Mountains alongside Alpine fauna on the Tibetan Plateau suggests that the modern distribution patterns may have already existed since the Pliocene.

Modified tragus edge incision and transmasseteric anteroparotid approach to condyle reconstruction.

OBJECTIVES: This study aimed to analyze the application value of a modified tragus edge incision and transmasseteric anteroparotid approach to condyle reconstruction. METHODS: Condyle reconstruction was performed in 16 patients (9 females and 7 males) with modified tragus edge incision and transmasseteric anteroparotid approach. After regular follow-up, the function of condyle reconstruction was evaluated by clinical indicators, such as parotid salivary fistula, facial nerve function, mouth opening, occlusal relationship, and facial scar. The morphology of rib graft rib cartilage was evaluated by imaging indicators, such as panoramic radiography, CT, and three-dimensional CT image reconstruction. RESULTS: At 6-36 months postoperative follow-up, all patients had good recovery of facial appearance, concealed incisional scar, no parotid salivary fistula, good mouth opening, and occlusion. One case had temporary facial paralysis and recovered after treatment. Radiographic evaluation further showed that costochondral graft survived in normal anatomic locations. CONCLUSIONS: The modified tragus edge incision and transmasseteric anteroparotid approach can effectively reduce parotid salivary fistula and facial nerve injury in condylar reconstruction. The surgical field was clearly exposed, and the incision scar was concealed without increasing the incidence of other complications. Thus, this approach is worthy of clinical promotion.

Flexure-resistant and additive-free poly (L-lactic acid) hydrophobic membranes fabricated by slow phase separation.

PLLA membranes with excellent ductility were successfully prepared by a simple solvent evaporation-induced precipitation method, without any additive. The excellent mechanical properties are mainly attributed to the interconnecting pore morphology and the plastic deformation of the pore wall during the stretching process. The interconnecting pore morphology is determined by delaying non-solvent diffusion and molecular chain pre-nucleation. It was found that the average pore size gradually decreased from 19.25 µm to 6.71 µm as the concentration of the polymer solution increased from 0.03 g/ml to 0.10 g/ml, and the elongation at break of the membrane can reach 130.8%. The crystallinity is between 33.4% and 44.5%, and the crystal form is a perfect α crystal. Membrane with interconnecting pore structure contributes to the formation of 91.2% porosity. Furthermore, the solvent evaporation-induced precipitation method can also form surfaces containing micro-nano structures which significantly improves surface hydrophobicity. The combination of high porosity and hydrophobicity makes the membrane potentially applicable to the field of oil-water separation.

A20 alleviated caspase-1-mediated pyroptosis and inflammation stimulated by Porphyromonas gingivalis lipopolysaccharide and nicotine through autophagy enhancement.

Periodontitis is the leading cause of tooth loss, and patients with smoking habits are at an increased risk of developing periodontitis. A20 (the tumor necrosis factor alpha-induced protein 3, TNFAIP3) is one of the key regulators of inflammation and cell death in numerous tissues. Emerging researches indicated A20 as a fundamental molecule in the periodontal tissue. This study was to evaluate the role of A20 against cell death and inflammation in periodontitis and to elucidate the underlying mechanisms. In our study, western blot, autophagy detection, and transmission electron microscopy showed that lipopolysaccharide from Porphyromonas gingivalis (Pg.LPS) and nicotine (NI) could enhance the activation of autophagy. Pg.LPS and NI induce the pyroptosis of human periodontal ligament cells (hPDLCs), as evidenced by the decrease of membrane integrity and the increase of NLRP3, GSDMD, GSDMD-N, caspase-1 activity, and the pro-inflammatory cytokines of IL-1ß, IL-6, TNF-α. Further researches were focused on that A20, an ubiquitin-editing enzyme, was linked to hPDLCs pyroptosis. Overexpression or silencing A20 could diminish or aggravate pyroptosis in hPDLCs by the modulation of autophagy. The above results demonstrated that A20 dictated the cross-talk between pyroptosis and autophagy. Overexpression of A20 enhanced autophagy to reduce pyroptosis, and thus alleviating inflammation, suggesting that A20 may be a potent target in the treatment of periodontitis.

Traditional Uses, Chemistry, Pharmacology, Toxicology and Quality Control of Alhagi sparsifolia Shap.: A Review.

Alhagi sparsifolia Shap. (Kokyantak) is a ethnic medicine used in the Uyghur traditional medicine system for the treatment of colds, rheumatic pains, diarrhea, stomach pains, headaches, and toothaches, in addition to being an important local source of nectar and high-quality forage grass, and playing a crucial role in improving the ecological environment. Currently, approximately 178 chemical constituents have been identified from A. sparsifolia, including flavonoids, alkaloids, phenolic acids, and 19 polysaccharides. Pharmacological studies have already confirmed that A. sparsifolia has antioxidant, anti-tumor, anti-neuroinflammatory effects, hepatoprotective effects, renoprotective effects and immune regulation. Toxicological tests and quality control studies reveal the safety and nontoxicity of A. sparsifolia. Therefore, this paper systematically summarizes the traditional uses, botany, phytochemistry, pharmacology, quality control and toxicology of A. sparsifolia, in order to provide a beneficial reference of its further research.

[Distribution and Sources of Microplastics in Farmland Soil Along the Fenhe River].

This study investigated the distribution and sources of microplastics smaller than 1 mm in farmland soil along the Fenhe River. Microplastics in soil samples were separated and extracted using the traditional density centrifugation method. The quantity and type of microplastics were examined with a stereomicroscope. The micro-morphology of plastic particles were observed with a scanning electron microscope-energy dispersive spectrometer. The chemical composition was determined using Fourier transform infrared spectroscopy. The results indicate that the average abundance of microplastics in farmland soil along the Fenhe River is 290.5 n ·kg-1. These microplastics occur as fibers, films, fragments, and foams. Fiber microplastics are the most abundant, accounting for 52.67% of the total, and are mostly composed of polyethylene. Films and fragments mainly consist of polypropylene whereas the foams consist of polystyrene. Soil samples from different parts of the Fenhe River can be ranked according to the microplastics content in the following order:downstream>midstream>upstream. The abundance of microplastics in soil from the downstream region of the Fenhe River was 500.0 n ·kg-1, twice that of from the upstream and midstream regions. The results of the random forest model indicate that the sources of microplastics in farmland soil along the Fenhe River are closely related to the amount of agricultural films, population, gross domestic product, and industrial production. Among these factors, the amount of agricultural films is a key factor that influences the occurrence of microplastics in farmland soil along the Fenhe River.

[Kinetic spectrophotometric study on hemolytic process of polysorbate 80].

To establish kinetic assay method for the analysis of hemolysis and to investigate dynamic hemolytic process of polysorbate 80. The UV-VIS spectrum of heme changes when hemoglobin is released continuously during the hemolytic process. Therefore, dynamic hemolytic curve was determined as a new way to characterize the kinetic process of interaction between polysorbate 80 and red blood cells. The effect of polysorbate 80 on blood cells could be perfectly investigated by the hemolytic dynamics. Dynamic hemolytic parameters of polysorbate 80 were calculated according to the hemolytic curves. The constants of hemolytic rate and maximum hemolytic rate of polysorbate 80 had fine linear relationships at the range of 1-20 mg x mL(-1) and 5-20 mg x mL(-1), respectively. In comparison with the present official method such as macroscopic observation and static spectrophotometric methods, kinetic spectrophotometry has the advantages of real time, on-line determination, sensitive, objective, good reproducibility and 2-dimensional information acquired. Therefore, as a biological technique, kinetic spectrophotometry could be applied to evaluate the quality of polysorbate 80 and to screen other solubilizing excipients.

In vivo tissue response and degradation behavior of PLLA and stereocomplexed PLA nanofibers.

Biocompatibility of PLLA and stereocomplexed PLA nanofibers was evaluated by subcutaneous implantation in rats for 4-12 weeks. Characterization of the nanofibers was performed by GPC, SEM, wide-angle X-ray diffraction, and optical microscopy of hematoxylin-eosin stained ultrathin sections of explanted nanofibers. Stereocomplexed PLA nanofiber showed slower degradation than PLLA nanofiber and thus retained their shape after prolonged implantation. Furthermore, stereocomplexed PLA nanofiber caused milder inflammatory reaction than PLLA nanofiber. These results offer the potential use of PLLA and stereocomplexed PLA nanofibers as a biomaterial for short-term and long-term tissue regeneration, respectively. Stereocomplexed PLA nanofiber after in vitro degradation showed smaller degree of swelling than PLLA nanofiber. Taking the results of in vivo degradation together with in vitro degradation into consideration, bioabsorption mechanism of the in vivo degradation of the nanofibers is proposed.