Bacteriocin Isolated from Lactobacillus Rhamnosus L34 Has Antibacterial Effects in a Rabbit Model of Infection After Mandible Fracture Fixation.

BACKGROUND Rigid internal fixation (RIF) technology is a recently developed fracture fixation technique in which use of specific antibiotics before and after the operation and timely treatment of local infections is necessary. MATERIAL AND METHODS The bacteriocins were isolated from Lactobacillus rhamnosus L34. Twenty-four New Zealand White female rabbits were divided into 2 groups: bacteriocins and control group. After mandible fracture fixation, the rabbits were infected with S. aureus and subsequently injected with either bacteriocins or saline. The biofilm samples were harvested from rabbits euthanized on the 1st, 3rd, and 5th days and observed using a fluorescence microscope. Blood samples were collected at 1 h, 12 h, 1 day, 3 days, and 5 days after the injection of either bacteriocin or saline to test the level of C-reactive protein and TNF-α. RESULTS Significant differences in the biofilm formation were evident between the bacteriocins and saline treatment group on days 1, 3, and 5. Moreover, the serum levels of TNF-α and CRP after treatment with bacteriocins were significantly lower than in controls. CONCLUSIONS Use of bacteriocins isolated from Lactobacillus rhamnosus L34 may be a promising way to control infections of mandible fracture after internal fixation in vivo.

Antibacterial Effect of Bacteriocin Isolated From Lactobacillus Plantarum ATCC 8014 on Postoperative Infection of Mandibular Fracture In Vivo.

OBJECTIVE: The primary objective of this study was to verify the effects of bacteriocin in treatment of postoperative infection of mandibular fracture in vivo. METHODS: Eighty-two mice were inoculated intravenously with staphylococcal suspensions. Bacterial cultures were obtained from implants. Blood samples were collected at 1, 2, 4, 6, and 8 hours after the injection of bacteriocins. RESULTS: Bacteriocins have significant inhibitory effects on Staphylococcus aureus (P < 0.05) and there are significant differences interleukin (IL)-8 and IL-10 in serum (P < 0.05). CONCLUSIONS: Bacteriocin isolated from L plantarum may be one of promising ways to control postoperative infection of mandibular fracture in vivo.

[Influence of gelatin particle size and gelatin/calcium phosphate cement ratio on repairing potency of composite artificial bone material].

OBJECTIVE: To investigate the influence of gelatin particle (GP) size and gelatin/calcium phosphate cement (GP/CPC) ratio on repairing potency of comparison artificial bone material. METHODS: Composite GP/CPC materials with different GP size (100~200 µm vs. 200~300 µm) and ratio(5% vs. 10%) were prepared. Physiochemical and biological properties, including porosity, resistance to compression, ultrastructure and biocompatibility were compared among 4 groups of GP/CPC materials. Different GP/CPC materials were used to repair the critical-size cranial bone defect in rabbit model, and the histology and newly formed bone inside scaffolds (nBIS) were examined and compared among different groups. RESULTS: GP/CPC with GP of 200~300 µm possessed larger micropores than that with GP of 100~200 µm (P<0.05). The GP/CPC containing 10% GP had higher porosity than that containing 5% GP (P<0.05). The animal model study showed that more new bone formed in those defects filled with GP/CPC containing 10% GP with 200~300 µm in size compared with GP/CPC containing 5% GP with 100~200 µm in size (P<0.05). While GP/CPC containing 5% GP with 100~200 µm in size showed a higher level of resistance to compression. CONCLUSION: Both the particle size of GP and its ratio in the GP/CPC affect the properties of the composite biomaterials and their role in bone repairing. In particular, the GP/CPC containing 10% GP with 200~300 µm in size is most suitable for repairing critical-size cranial bone defect in animal model.

Solar-driven methanogenesis with ultrahigh selectivity by turning down H2 production at biotic-abiotic interface.

Integration of methanogens with semiconductors is an effective approach to sustainable solar-driven methanogenesis. However, the H2 production rate by semiconductors largely exceeds that of methanogen metabolism, resulting in abundant H2 as side product. Here, we report that binary metallic active sites (namely, NiCu alloys) are incorporated into the interface between CdS semiconductors and Methanosarcina barkeri. The self-assembled Methanosarcina barkeri-NiCu@CdS exhibits nearly 100% CH4 selectivity with a quantum yield of 12.41 ± 0.16% under light illumination, which not only exceeds the reported biotic-abiotic hybrid systems but also is superior to most photocatalytic systems. Further investigation reveal that the Ni-Cu-Cu hollow sites in NiCu alloys can directly supply hydrogen atoms and electrons through photocatalysis to the Methanosarcina barkeri for methanogenesis via both extracellular and intracellular hydrogen cycles, effectively turning down the H2 production. This work provides important insights into the biotic-abiotic hybrid interface, and offers an avenue for engineering the methanogenesis process.

Evaluation of the antibacterial effects and mechanism of Plantaricin 149 from Lactobacillus plantarum NRIC 149 on the peri-implantitis pathogens.

Peri-implantitis is a common reversible disease after tooth implantation, caused by a variety of pathogenic microorganisms. Based on non-surgical or surgical treatment principles, supplementation by local or systemic drugs might enhance treatment efficacy. Porphyromonas gingivalis (Pg) (ATCC 33,277) and Prevotella intermedius (Pi) (ATCC 25,611) were used as test strains. The effects of Pln 149 on the biofilm formation and growth of four periodontal pathogens were evaluated by RT-PCR, fluorescence microscopy, and scanning electron microscopy. The antibacterial mechanism was tested by the patch-clamp technique. The cytotoxicity of Pln 149 (125 µg/ml) to bone marrow stromal cell (BMSC) was assessed using an MTT assay. Pln 149 exhibited significant inhibitory effects on Pg and Pi (P < 0.05), with significant differences in the biofilm images of fluorescence microscope and scanning electron microscope (P < 0.05). Pln 149 could change the sodium channel currents and exerted no cytotoxicity on bone marrow stromal cell. Pln 149 could inhibit the biofilm formation and growth of periodontal pathogens. Considering the absence of antimicrobial resistance and cytotoxicity, we suggest that the Pln 149 from Lactobacillus plantarum 149 might be a promising option for managing peri-implantitis.

Hybrid transvaginal natural orifice transluminal endoscopic surgery of radical sigmoidectomy for sigmoid colon cancer.

BACKGROUND: Transvaginal natural orifice transluminal endoscopic surgery (NOTES) is a surgical technique - "scarless" abdominal operations performed with a multi-channel endoscope passed through a natural orifice (mouth, urethra, anus, vagina etc.) and offers less invasive and more excellent cosmetic results [1]. It is regarded as safe and feasible in patients with benign disease [2,3]. The first case of pure NOTES for sigmoid colon cancer was reported in 2012 [4]. We describe here a case of curatively intended resection for early-stage sigmoid colon cancer using the hybrid transvaginal NOTES approach. METHODS: This video demonstrates the case of a 52-year-old woman with sigmoid colon cancer treated by hybrid transvaginal NOTES. Her body mass index was 20.4 kg/m2. A laparoscope was inserted above the umbilicus and tumor's position was located. Two 5 mm trocars inserted in the right lower abdominal quadrant were mainly used for the assistant's instruments to provide traction and exposure. A single-port was inserted into the abdominal cavity transvaginally through the colpotomy. Then all the procedures were performed transvaginally with conventional rigid laparoscopic instruments. The sigmoid colon was mobilized using a lateral to medial approach. Then the root of the inferior mesenteric artery and the inferior mesenteric vein were divided with absorbable clips. After complete isolation of the proximal rectum, the rectum was transected 5 cm distal to the lesion with a linear stapler inserted through the single port. The proximal resection margin of descending colon was identified and the transection of the colon was performed. The specimen was removed transvaginally. The colon was then exteriorized and the anvil was fixed in the colon. An end-to-end anastomosis was performed using a circular stapler, and a leak test was done. RESULTS: The operative time and estimated blood loss were 182 min and 50 mL. A 20 cm long segment of sigmoid colon was resected with negative tumor margins, and 16 lymph nodes were harvested. There was no intraoperative or postoperative morbidity. The patient was with out-of-bed activity on day 1, fluid diet on day 2, bowel movement on day3, and the drainage tube and catheter removing on day 4. On day 5, she was discharged. Pathological examination revealed a moderately-differentiated adenocarcinoma: 50 × 45 × 10 mm, with growing into subserosa, without vascular or nervous invasion, pT3N0M0 and pStage IIA. There were two scars less than 5 mm and one scar less than 10 mm visible on the abdominal wall at one month. The patient was alive without recurrence after one year's follow-up. CONCLUSION: Hybrid transvaginal NOTES of radical sigmoidectomy may be safe and feasible for selected patients with sigmoid colon cancer and give less pain, potentially low rates of complication, faster recovery, and better cosmesis. A future large study is warranted to better evaluate this procedure. Although there are many reasons for skepticism, there is undoubted interest in this field from both surgeon and patient.

Development and comparison of forecast models of hand-foot-mouth disease with meteorological factors.

Hand-foot-mouth disease (HFMD) is an acute intestinal virus infectious disease which is one of major public health problems in mainland China. Previous studies indicated that HFMD was significantly influenced by climatic factors, but the associated factors were different in different areas and few study on HFMD forecast models was conducted. Here, we analyzed epidemiological characteristics of HFMD in Yiwu City, Zhejiang Province and constructed three forecast models. Overall, a total of 32554 HFMD cases were reported and 12 cases deceased in Yiwu City, Zhejiang Province. The incidence of HFMD peaked every other year and the curve of HFMD incidence had an approximately W-shape. The majority of HFMD cases were children and 95.76% cases aged ≤5 years old from 2008 to 2016. Furthermore, we constructed and compared three forecast models using autoregressive integrated moving average (ARIMA) model, negative binomial regression model (NBM), and quasi-Poisson generalized additive model (GAM). All the three models had high agreements between predicted values and observed values, while GAM fitted best. The exposure-response curve of monthly mean temperature and HFMD was approximately V-shaped. Our study explored epidemiological characteristics of HFMD in Yiwu City and provided accurate methods for early warning which would be great importance for the control and prevention of HFMD.

Esophageal foreign bodies in adults with different durations of time from ingestion to effective treatment.

Objective This study was performed to identify the differences in clinical characteristics, operative methods, complications, and postoperative hospitalization stays for adults with esophageal foreign bodies with different durations of time from ingestion to effective treatment. Methods We retrospectively reviewed the medical records of 221 patients with a diagnosis of a foreign body in the esophagus, confirmed by rigid esophagoscopy, flexible esophagoscopy, or surgery. The differences between the two groups (Group A, ≤24 hours from ingestion to effective treatment; Group B, >24 hours from ingestion to effective treatment) were analyzed. Results Sharp foreign bodies comprised the majority of objects in the two groups, including jujube pits, bones (excluding fish bones), fish bones, dentures, and seafood shells. Foreign bodies located in the upper esophagus were more commonly observed in Group A than B. Significant differences were observed in the complication rate and length of postoperative hospitalization stays. Adults with esophageal foreign bodies had a high complication rate. Conclusions Rigid esophagoscopy can be used to remove sharp and bulky foreign bodies if more effective methods are unavailable. Effective treatment within 24 hours resulted in fewer complications and shorter postoperative hospitalization stays.

[Titanium oxide layer on biomedical titanium alloy deposited by ion beam enhanced deposition].

Ion beam enhanced deposition (IBED) has been applied to prepare titanium oxide layer on titanium alloy (Ti6A14V) in order to improve its biocompatibility. The layer on titanium alloy is even, and the elements Al and V in substrate are not detected. The layer is composed of TiO containing nitrogen oriented along (111) plane. The critical load of the layer in scratch test is 16.8 N. Morphological observation reveals the layer ends in a failure caused by plastic deformation.

[Preparation and properties of hydroxyapatite/epoxy composite].

The hydroxyapatite (HA) powder surface modified with silane coupling agent was used to prepare HA/epoxy composite. It was found that silane has greatly improved the dispersion of HA in epoxy. The composite has good in vitro bioactivity and biocompatibility with 40 wt% HA, and the flexural modulus is close to that of natural bone, but its strength is lower than that of natural bone. So the composite needs further reinforcement in some way or other.

Anterior retropharyngeal approach to C1 for percutaneous vertebroplasty under C-arm fluoroscopy.

BACKGROUND CONTEXT: Percutaneous vertebroplasty (PVP) has proven to be a valuable palliative treatment option for patients with medically refractory painful osteolytic metastases of the spine. Percutaneous vertebroplasty of the atlas has been reported in only seven articles and has been performed with different techniques and approaches. PURPOSE: To describe the technique we used to perform PVP of a lytic lesion of the lateral mass of C1 via anterior retropharyngeal approach guided by C-arm fluoroscopy. STUDY DESIGN: A technical report. PATIENT SAMPLE: It included a 75-year-old man with known metastatic lung carcinoma and incapacitating right suboccipital and neck pain refractory to conventional medical treatment. Radiologic evaluation showed revealed osteolytic destruction of C1 and C2, mainly invading the right lateral mass of C1 and the vertebral body of C2. OUTCOME MEASURES: The right suboccipital and neck pain was measured using the visual analog scale (VAS). METHODS: Under C-arm fluoroscopy, a novel anterior retropharyngeal approach, through the vertebral body of C2 into the metastatic osteolytic vertebral lesion of C1, was performed to achieve the PVP in C1 followed by a PVP in C2. RESULTS: Immediately after the operation, the patient reported substantial pain relief (from VAS 9/10 preoperatively to 3/10). At 12 hours postoperatively, the range of motion was also improved. There were no surgery-related complications. The immediately postoperative cervical plain film and computed tomography scan showed adequate filling of the osteolytic lesion without the obvious leakage of bone cement. Clinical follow-up at 3 months revealed that this pain condition was improved and maintained (VAS 1/10). CONCLUSIONS: When the transoral approach is unsuitable or contraindicated, the anterior retropharyngeal approach could be an efficacious alternative in selected patients with C1 metastasis, providing adequate filling of bone cement and significant pain relief. Based on our preliminary exploration, only assisted by C-arm fluoroscopy, this approach is feasible to achieve PVP in C1 under local anesthesia and intravenous analgesia. Nevertheless, when considering the substantial potential risks, this technically challenging procedure should be performed by experienced operators.

In vitro and in vivo tests of hydrothermally synthesised hydroxyapatite coating.

High pure and crystalline Hydroxyapatite (HA) coatings on titanium alloy were prepared by hydrothermal synthesis (HS) of plasma-sprayed (PS) precursors from brushite powders (HS-HA). In vitro and in vivo tests were done to evaluate its biological property. The HS-HA coating was compared with the current PS-HA coating. Cultures of the primary osteoblasts on these two HA coatings showed similar cell attachment, proliferation and alkaline phosphatase (ALP) expression. The cell morphology on the coatings was demonstrated by scanning electron microscopy (SEM). The cell spread well at 1 day after seeding culture and the extracellular matrix was secreted after 14 days culture. Histomorphometric analysis was conducted on samples implanted in femoral bone of four dogs for 1 and 3 months, and bone-implant contact percentage was evaluated by light microscopy. The calcium and phosphate distribution on the interface of bone-implant was analysed by SEM and electron dispersive X-ray (EDX) analysis. The results show the osteoconduction of HS-HA coated implants.

Enhanced osteoblast functions on RGD immobilized surface.

Many methods are currently under investigation to improve the integration of dental implants to surrounding bones. Among these methods, peptide-modified surfaces have been highlighted as one of the most promising. Our study, aimed at the cellular response to RGD-immobilized surface in vitro, investigated the basis for designing a bone-active surface coating with RGD-containing peptide. Gold-coated titanium surfaces were used as indicative control surfaces for peptide immobilization. Using self-assembly monolayer techniques, 2 types of peptides, RGDC (Arg-Gly-Asp-Cys) and RDGC (Arg-Asp-Gly-Cys), were immobilized onto the gold surfaces. Surface justification was realized through X-ray photoelectron spectroscopy and Fourier transform infrared spectra. Primary calvarial osteoblasts were cultured on RGDC, RDGC, and non-peptide-coated surfaces. Cell attachment, morphology, proliferation, and expression of osteocalcin (OC) messenger RNA (mRNA) were assessed using cell counting, immunolabeling fluorescence microscopy, and Northern blot assay. Four and 8 hours after culture, cell attachment was enhanced on RGDC surfaces. Correspondingly, increased cell spreading and significantly greater cell proliferation were also observed in cells grown on the RGDC-coated surfaces. More importantly, osteoblasts on RGDC surfaces showed earlier and significant OC mRNA expression at day 15 compared with controls having the similar expression at day 21. These results provided evidence of the enhanced functions of osteoblasts cultured on the RGDC-modified surfaces, which might be effective in improving osseointegration for dental implants.

[Compounding techniques of bioactive ceramic and polymer biomaterials].

Some techniques of compounding bioactive ceramics and polymer biomaterials with mechanical and biological properties and the clinical applications of the composites produced are presented.

Enucleation combined with peripheral ostectomy: its role in the management of large cystic ameloblastomas of the mandible.

AIM: Aggressive resection of a large mandibular cystic ameloblastoma may cause severe deformity and dysfunction, while simple enucleation may carry a high risk of recurrence. The purpose of this study was to evaluate, in terms of both recurrence and the preservation of contour and function, the effectiveness of enucleation combined with peripheral ostectomy (Enu/PO) in managing large mandibular cystic ameloblastomas. MATERIALS AND METHODS: Fourteen patients who had large mandibular cystic ameloblastoma (11 unicystic, 3 multicystic) and had been treated with the Enu/PO were reviewed. RESULTS: The follow-up period was 19-117 months. Using Enu/PO, mandibular continuity was preserved in all patients, and only one patient complained of permanent lip numbness. With bone regeneration, the thinned bone plate significantly thickened and the residual cavity shrank. No pathological fracture occurred. There was recurrence in 3 patients. Two recurrences were treated with radical surgery, and the other with Enu/PO. No new recurrence was found thereafter. All patients were satisfied with their facial appearance. CONCLUSIONS: The Enu/PO technique is excellent in preserving appearance and functions and with a low risk of recurrence, is a reliable option for the management of large mandibular cystic ameloblastomas.

Multifocal Langerhans cell histiocytosis in an adult with a pathological fracture of the mandible and spontaneous malunion: A case report.

Langerhans cell histiocytosis (LCH) is rare in the adult population and even rarer with jaw involvement. The current study presents the case of a 39-year-old male who complained of recurrent pain, swelling of the gingiva and an occasional pus-like discharge in the right mandible for one year. The patient was previously prescribed antibiotics, but this did not resolve the problem. An initial panoramic radiograph showed an osteolytic lesion and bone fracture in the right mandible. Eight months later, a new radiograph showed the spontaneous malunion of the fractured mandible. The patient was eventually diagnosed with Langerhans cell histiocytosis by histopathology and immunohistochemistry. Further lesions were found in the ribs and ilium by nuclear bone scanning. The patient was subsequently treated with systemic chemotherapy, and the lesions are currently effectively being controlled. This study is the first to show that spontaneous intralesional bone regeneration may lead to reunification of the mandible fracture caused by LCH in an adult.

[Treatment of osteoporotic vertebral fractures with percutaneous balloon kyphoplasty using calcium phosphate cement].

OBJECTIVE: To assess the clinical outcomes of balloon kyphoplasty assisted with calcium phosphate cement (CPC) in treating osteoporotic vertebral fractures (OVF). METHODS: From January 2009 to January 2011, 26 patients with osteoporotic vertebral fractures were treated with balloon kyphoplasty assisted with CPC, including 31 vertebrae. There were 15 males and 11 females with an average age of (71.67 +/- 4.36) years old (ranged from 60 to 89 years). Course of disease was from 0.5 to 7 days with an average of 3.2 days. Clinical outcomes were assessed by the visual analogue scale (VAS) and the oswestry disability index (ODI). Vertebral height loss and kyphotic angle were measured by X-rays. RESULTS: All patients were followed up for 10 to 24 months with an average of 18 months. Before operation, 24 hours after operation and at final follow-up, VAS scores were 7.91 +/- 1.20, 3.22 +/- 1.12, 1.92 +/- 0.83, respectively; ODI scores were 40.00 +/- 1.15, 17.00 +/- 2.12, 13.00 +/- 1.42, respectivesly; vertebral heights were (18.21 +/- 3.21), (23.82 +/- 3.10), (21.85 +/- 3.24) mm, respectivesly; vertebral kyphosis angles were (18.21 +/- 3.21) degrees, (7.42 +/- 3.13) degrees, (10.01 +/- 3.11) degrees, respectivesly. There was significant difference between preoperation and 24 hours after operation, and between final follow-up and preoperation (P < 0.05). There was no significant difference between final follow-up and 24 hours after operation (P > 0.05). CONCLUSION: Balloon kyphoplasty assisted with calcium phosphate cement (CPC) is effective for the treatment of osteoporotic vertebral fractures (OVF), which can expeditiously relieve pain and effectively rebuild height of vertebral body and kyphotic angle, and also has advantages of minimal trauma and good security.

[Toxicity of niclosamide with plastic film mulching to fish].

OBJECTIVE: To observe the toxicity of niclosamide with plastic film mulching to fish. METHODS: A ditch with Oncomelania snails was selected as the study site, and it was divided into a control group and a molluscicide group. After the river closure, the molluscicidal group was sprayed with niclosamide with a dosage of 2 g/m2, and then covered with plastic film; no molluscicide measure was implemented in the control group. The toxicity of the molluscicide to carp fish in resting and flowing water environment was observed. RESULTS: In flowing water, the death rates of carp fry of the molluscicidal and control groups showed no statistical difference 7 d after the film mulching (P = 0. 680), and no carp fry died in the 2 groups after plastic film taking off for 4 d. The death rates of carp fry between the 3 sites (with a distance of 50, 100 and 150 m from the molluscicidal group, respectively) and the control group had no statistical difference 7 d after film mulching (P = 0.955), and no dead fry was discovered 4 d after taking off the film. In downstream, for the death rates of carp fry, there was no difference between the molluscicidal group and the control group (P = 0.376). The death rates of snails before and after the molluscicidal experiment showed a significant difference (P < 0.01). CONCLUSIONS: The technology of niclosamide molluscicide with plastic film mulching can not only improve the molluscicidal effect, but also avoid the toxicity to fish, which is suitable for special environment such as a fish pond.

In vitro efficacy of immuno-chemotherapy with anti-EGFR human Fab-Taxol conjugate on A431 epidermoid carcinoma cells.

The aims of this study were to generate a human Fab fragment against EGFR; conjugate it to paclitaxel (Taxol) as an immuno-chemotherapy agent; and investigate its in vitro anti-tumor efficacy on A431 epidermoid carcinoma cells. A431 cells (EGFR-positive), NIH 3T3 cells (EGFR-negative), and purified EGFR were used for subtractive panning on a human naïve Fab phage library to generate a human anti-EGFR Fab fragment that binds the EGFR extracellular domain in native conformation and subsequently internalizes it into the cytosol. The Fab was then conjugated with the chemotherapeutic Taxol, and cell proliferation inhibition and apoptosis (TUNEL) assays were conducted to determine the effect of this Fab-drug conjugate on A431 cells. The specificity and internalization property of this Fab were characterized by immunoprecipitation, fluorescence staining, flow cytometry, and Hum-Zap assay. The binding affinity to purified EGFR was 30 nM. The Fab-Taxol conjugate inhibited A431 cell proliferation at low concentrations and in a dose-responsive manner; more than 70% inhibition was observed at 52 pM. Furthermore, almost 100% of cells underwent apoptosis after treatment with Fab-Taxol at 26 pM for 48 hours. Our findings suggest that this Fab-Taxol conjugate could be a potential immuno-chemotherapeutic drug for clinical treatment of EGFR-overexpressing tumors.

Simvastatin causes the formation of cholesterol-rich remnants in mice lacking apoE.

Mice that lack apolipoprotein E (apoE) display a severe hypercholesterolemia, caused by the accumulation of apolipoprotein B-48 (apoB-48)-carrying remnants of chylomicrons and very-low-density lipoproteins in the plasma. Statins are potent inhibitors of cholesterol synthesis that, when administered to mice lacking apoE, cause paradoxical further increases in plasma cholesterol levels. In the present study, we examined the mechanisms responsible for this phenomenon. ApoE-deficient mice fed a chow diet containing simvastatin developed, as anticipated, an enhanced increase in plasma cholesterol and a decrease in plasma triglycerides. Fractionation of the plasma lipoproteins by FPLC revealed that the lipid changes were confined to the lipoprotein remnants. Western blot analysis of the remnants from the untreated and simvastatin-treated mice showed no differences in their apoB-48 content, indicating that both groups of animals accumulated similar numbers of remnant particles in the plasma. Following the injection of Triton WR-1339, the simvastatin-treated mice accumulated in the plasma significantly more cholesterol and significantly less triglycerides than the untreated animals. These results indicate that the enhanced hypercholesterolemia observed in apoE-deficient mice treated with simvastatin is not the result of an increased number of remnant particles in circulation but is caused by synthesis and secretion into the plasma of lipoproteins that are enriched in cholesterol and depleted of triglycerides.