Effect of artesunate on cardiovascular complications in periodontitis in a type I diabetes rat model and related mechanisms.

PURPOSE: Both cardiovascular disease and periodontitis are complications of diabetes that have a great impact on human life and health. Our previous research found that artesunate can effectively improve cardiovascular disease in diabetes and has an inhibitory effect on periodontal disease. Therefore, the present study aimed to explore the potential therapeutic possibility of artesunate in the protection against cardiovascular complications in periodontitis with type I diabetes rats and to elucidate the possible underlying mechanisms. METHODS: Sprague‒Dawley rats were randomly divided into the healthy, diabetic, periodontitis, diabetic with periodontitis, and artesunate treatment groups (10, 30, and 60 mg/kg, i.g.). After artesunate treatment, oral swabs were collected and used to determine changes in the oral flora. Micro-CT was performed to observe changes in alveolar bone. Blood samples were processed to measure various parameters, while cardiovascular tissues were evaluated by haematoxylin-eosin, Masson, Sirius red, and TUNEL staining to observe fibrosis and apoptosis. The protein and mRNA expression levels in the alveolar bone and cardiovascular tissues were detected using immunohistochemistry and RT‒PCR. RESULTS: Diabetic rats with periodontitis and cardiovascular complications maintained heart and body weight but exhibited reduced blood glucose levels, and they were able to regulate blood lipid indicators at normal levels after artesunate treatment. The staining assays suggested that treatment with 60 mg/kg artesunate has a significant therapeutic effect on myocardial apoptotic fibrosis. The high expression of NF-κB, TLR4, VEGF, ICAM-1, p38 MAPK, TGF-ß, Smad2, and MMP9 in the alveolar bone and cardiovascular tissue in the type I diabetes and type I diabetes with periodontitis rat models was reduced after treatment with artesunate in a concentration-dependent manner. Micro-CT showed that treatment with 60 mg/kg artesunate effectively alleviated alveolar bone resorption and density reduction. The sequencing results suggested that each model group of rats had vascular and oral flora dysbiosis, but artesunate treatment could correct the dysbacteriosis. CONCLUSIONS: Periodontitis-related pathogenic bacteria cause dysbiosis of the oral and intravascular flora in type I diabetes and aggravate cardiovascular complications. The mechanism by which periodontitis aggravates cardiovascular complications involves the NF-κB pathway, which induces myocardial apoptosis, fibrosis, and vascular inflammation.

[Establishment of three-dimensional measurement methods of nasolabial soft tissue for patients with maxillary protrusion].

OBJECTIVE: To establish a series of three-dimensional measurement methods of nasolabial soft tissue for maxillary protrusion patients by using 3dMD camera, and to evaluate preoperative and postoperative changes of the nasolabial soft tissue. METHODS: Three-dimensional facial photos of 30 female patients with maxillary protrusion [average age, (27.33±2.54) years] were taken by 3dMD camera preoperatively and at the end of postoperative 6 months or more. Then, 3dMD patient software was used to locate the selected landmarks at nasolabial region on the three-dimensional photos. Ten measurements, including soft tissue line distance, angle, curve distance and postoperative three-dimensional volume changes were measured twice with one week interval by 3 investigators, respectively. A standard consistency test calculated by the correlation coefficients (ICC) was performed between two sets of data (including all of the 10 measurements) for each investigator and among the three investigators to verify the repeatability. RESULTS: The average maxillary incisor retraction distance of the 30 subjects was (5.13±0.99) mm, and the average follow-up time was (11.07±5.11) months. The standard consistency test was performed between the two sets of data for each investigator, and the correlation coefficients (ICC) of the 10 measurements were all over 0.8 for each investigator (P>0.05). The standard consistency test was performed among the three surveyors, with the result that the ICC of the width of the bilateral inner canthus, the height of the nose, the height of nasal tip, nasolabial angle, philtrum length, the curve height of upper vermilion and the height of upper lip were greater than 0.8 (P>0.05), and the ICC of the distance between SbalSbal, length of nasal dorsum and three-dimensional volume change of upper lip were 0.680, 0.627 and 0.528, respectively (P>0.05). CONCLUSION: 3dMD camera and 3dMD patient software can be used to measure and analyze the three-dimensional morphology of the nasolabial soft tissue for patients with maxillary protrusion preoperatively and postoperatively, and it is relatively accurate and reliable. However, the repeatability of three-dimensional positioning of the nasal tip point and the Sbal is slightly worse resulting in the lower value of the ICC of the distance between SbalSbal and length of nasal dorsum, as well as the upper lip three-dimensional volume change after the operation.

[Accuracy analysis of computer assisted navigation for condylectomy via intraoral approach].

OBJECTIVE: To explore the application accuracy of virtual preoperative plan after the condylectomy via intraoral approach under computer assisted surgical navigation, and to analyze the location and cause of the surgical deviation to provide reference for the surgical procedure improvement in the future. METHODS: In the study, 23 cases with condylar hypertrophy (11 with condylar osteochondroma and 12 with condylar benign hypertrophy) in Department of Oral and Maxilloficial Surgery, Peking University School and Hospital of Atomatology from December 2012 to December 2016 were treated by condylectomy via intraoral approach under computer assisted surgical navigation. The patient's spiral CT data were imported into ProPlan software before operation, and the affected mandibular ramus was reconstructed three-dimensionally. The condylar osteotomy line was designed according to the lesion range, and the preoperative design model was generated and introduced into the BrainLab navigation system. Under the guidance of computer navigation, the intraoral approach was used to complete the condylar resection according to the preoperative design of the osteotomy line. Cranial spiral CT of the craniofacial region was taken within one week after operation. three-dimensional reconstruction of the mandibular ramus at the condylectomy side was performed, and the condylar section was divided into six segments (anterolateral, anterior, anteromedial, posteromedial, posterior, and posterolateral) and the corresponding regional measurement points P1 to P6 were defined. Then the preoperative virtual model and the postoperative actual model were matched by Geomagic studio 12.0 to compare the differences and to analyze the accuracy of the operation. RESULTS: All the patients had successfully accomplished the operation and obtained satisfactory results. Postoperative CT showed that the condyle lesion was completely resected, and the condylar osteotomy line was basically consistent with the surgical design. No tumor recurrence or temporomandibular joint ankylosis during the follow-up period. The postoperative accuracy analysis of the condylar resection showed that the confidence intervals measured by the six groups of P1 to P6 were (-2.26 mm, -1.89 mm), (-2.30 mm, -1.45 mm), (-3.37 mm, -2.91 mm), (-2.83 mm, -1.75 mm), (-1.13 mm, 0.99 mm), and(-1.17 mm, 0.17 mm), where P3 group was different from the other 5 groups. There was no significant difference between the P5 and P6 groups and the difference between the other four groups was statistically significant. CONCLUSION: Under the guidance of computer navigation, the intraoral approach can be performed more accurately. The surgical deviation of each part of the osteotomy surface is mainly due to excessive resection. The anterior medial area of the anterior medial condyle represents the most excessive resection. The posterior and posterior lateral measurement points represent the posterior condylar area. The average deviation is not large, but the fluctuation of the deviation value is larger than that of the other four groups. The accuracy of computer-assisted subtotal resection has yet to be improved.

Osteogenic potential of three different autogenous bone particles harvested during implant surgery.

OBJECTIVES: The aim was to compare the osteoblast activity and osteogenic potential of autogenous bone particles harvested using three different techniques and determine the most advantageous method of collecting autogenous bone particles. SUBJECTS AND METHODS: Bone particles were harvested from 20 patients during dental implant surgery using bone scraping, low-speed drilling and bone trap filtering. After the osteoblasts were cultured, cell proliferation, migration, mineralization, transcription of osteogenesis-related genes, secretion of osteogenesis-related proteins and osteoinductive protein content in the bone particle matrix were evaluated. RESULTS: Osteoblast activity and osteogenic potential were higher in bone samples harvested by scraper or low-speed drilling than in samples harvested by bone trap filter. Although these parameters were slightly lower in the low-speed drilling group than in the scraper group, significant differences were found only in bone Gla protein levels. However, the levels of osteoinductive proteins in the bone particle matrix were significantly higher in the low-speed drilling group than in the scraper group. CONCLUSIONS: Low-speed drilling is a recommendable and effective technique for collecting autogenous bone particles. In implant operations, low-speed drilling can be considered the first-line option, and if the quantity of harvested bone is insufficient, bone shavings obtained by the scraper may be considered.

Predictive factors for inadequate colon preparation before colonoscopy.

BACKGROUND: It could be helpful to ascertain which patients are at risk of poor bowel preparation prior to performing sedated colonoscopy. The aim of the present study was to identify the predictive factors for poor colon preparation prior to colonoscopy. METHODS: A prospective study was performed at Kaohsiung Chang Gung Memorial Hospital, Taiwan, from September 2011 to May 2013. Patient characteristics, food consumed within 2 days of colonoscopy, volume of polyethylene glycol (PEG) solution, interval between completing PEG and examination, number of bowel movements, and character of the last stool were evaluated. RESULTS: Seven hundred and three patients were enrolled (mean age 50.3 ± 11.6 years, 43 % female). In univariate analysis, character of the last stool (<0.001), body weight (p = 0.007), body mass index (p = 0.047), waist circumference (p = 0.008), buttock girth (p = 0.016), meal residue score (<0.001), and interval between end of PEG and colonoscopy (p = 0.01) were related to inadequate colon preparation. In multivariate analysis, waist circumference (p < 0.001), meal residue score (p < 0.001), and characteristics of last stool (p < 0.001) were variables that predicted poor colon preparation. CONCLUSIONS: Patients who have consumed a high residue diet and/or who report that their last stool is semisolid are likely to have poor bowel preparation, and consideration could be given to rescheduling the examination.

[Diversity of root canal morphology in mandibular first premolars and its clinical strategies].

It is a basic prerequisite for the successful completion of endodontic treatment to thoroughly understand the root canal space anatomy. With the development of dental devices in dentistry, the root canal morphology of the mandibular first premolars can be presented in more detail. Before conducting root canal therapy on the mandibular first premolar with complex root canal morphology, it should be necessary to evaluate the potential difficulties and risks for making an appropriate treatment plan. The present paper reviews the research progress on the diversities of root canal morphology in mandibular first premolars in recent years, and then makes technologic recommendations based on the morphology diversities.

Enhanced bioavailability of a poorly water-soluble weakly basic compound using a combination approach of solubilization agents and precipitation inhibitors: a case study.

Poorly water-soluble weakly basic compounds which are solubilized in gastric fluid are likely to precipitate after the solution empties from the stomach into the small intestine, leading to a low oral bioavailability. In this study, we reported an approach of combining solubilization agents and precipitation inhibitors to produce a supersaturated drug concentration and to prolong such a drug concentration for an extended period of time for an optimal absorption, thereby improving oral bioavailability of poorly water-soluble drugs. A weakly basic compound from Johnson and Johnson Pharmaceutical Research and Development was used as a model compound. A parallel microscreening precipitation method using 96-well plates and a TECAN robot was used to assess the precipitation of the tested compound in the simulated gastric fluid (SGF) and the simulated intestinal fluid (SIF), respectively, for lead solubilizing agents and precipitation inhibitors. The precipitation screening results showed vitamin E TPGS was an effective solubilizing agent and Pluronic F127 was a potent precipitation inhibitor for the tested compound. Interestingly, the combination of Pluronic F127 with vitamin E TPGS resulted in a synergistic effect in prolonging compound concentration upon dilution in SIF. In addition, HPMC E5 and Eudragit L100-55 were found to be effective precipitation inhibitors for the tested compounds in SGF. Furthermore, optimization DOE study results suggested a formulation sweet spot comprising HPMC, Eudragit L 100-55, vitamin E TPGS, and Pluronic F127. The lead formulation maintained the tested compound concentration at 300 µg/mL upon dilution in SIF, and more than 70% of the compound remained solubilized compared with the compound alone at <1 µg/mL of its concentration. Dosing of the solid dosage form predissolved in SGF in dogs resulted in 52% of oral bioavailability compared to 26% for the suspension control, a statistically significant increase (p = 0.002). The enhanced oral bioavailability of the tested compound could be attributed to generation and prolongation of a supersaturated drug concentration in vivo by the solubilizing agents and precipitation inhibitors. The study demonstrates that the combination approach of solubilization agents and precipitation inhibitors provides improved oral bioavailability for a poorly water-soluble weakly basic compound.

Dual delivery for stem cell differentiation using dexamethasone and bFGF in/on polymeric microspheres as a cell carrier for nucleus pulposus regeneration.

This study aimed to investigate the feasibility of the nanostructured 3D poly(lactide-co-glycolide) (PLGA) constructs, which are loaded with dexamethasone (DEX) and growth factor embedded heparin/poly(L-lysine) nanoparticles via a layer-by-layer system, to serve as an effective scaffold for nucleus pulposus (NP) tissue engineering. Our results demonstrated that the microsphere constructs were capable of simultaneously releasing basic fibroblast growth factor and DEX with approximately zero order kinetics. The dual bead microspheres showed no cytotoxicity, and promoted the proliferation of the rat mesenchymal stem cells (rMSCs) by lactate dehydrogenase assay and CCK-8 assay. After 4 weeks of cultivation in vitro, the rMSCs-scaffold hybrids contained significantly higher levels of sulfated GAG/DNA and collagen type II than the control samples. Moreover, quantitative real time PCR analysis revealed that the expression of disc-matrix proteins including collagen type II, aggrecan, and versican in the rMSCs-scaffold hybrids was significantly higher than that in the control group, whereas the expression of osteogenic differentiation marker (collagen type I) was decreased. Taken together, these data indicate that Dex/bFGF PLGA microspheres could be used as a scaffold to improve the rMSCs growth and differentiating into NP like cells, and reduce the inflammatory response for IVD tissue engineering.

A replication-competent adenovirus-vectored influenza vaccine induces durable systemic and mucosal immunity.

BACKGROUNDTo understand the features of a replicating vaccine that might drive potent and durable immune responses to transgene-encoded antigens, we tested a replication-competent adenovirus type 4 encoding influenza virus H5 HA (Ad4-H5-Vtn) administered as an oral capsule or via tonsillar swab or nasal spray.METHODSViral shedding from the nose, mouth, and rectum was measured by PCR and culturing. H5-specific IgG and IgA antibodies were measured by bead array binding assays. Serum antibodies were measured by a pseudovirus entry inhibition, microneutralization, and HA inhibition assays.RESULTSAd4-H5-Vtn DNA was shed from most upper respiratory tract-immunized (URT-immunized) volunteers for 2 to 4 weeks, but cultured from only 60% of participants, with a median duration of 1 day. Ad4-H5-Vtn vaccination induced increases in H5-specific CD4+ and CD8+ T cells in the peripheral blood as well as increases in IgG and IgA in nasal, cervical, and rectal secretions. URT immunizations induced high levels of serum neutralizing antibodies (NAbs) against H5 that remained stable out to week 26. The duration of viral shedding correlated with the magnitude of the NAb response at week 26. Adverse events (AEs) were mild, and peak NAb titers were associated with overall AE frequency and duration. Serum NAb titers could be boosted to very high levels 2 to 5 years after Ad4-H5-Vtn vaccination with recombinant H5 or inactivated split H5N1 vaccine.CONCLUSIONReplicating Ad4 delivered to the URT caused prolonged exposure to antigen, drove durable systemic and mucosal immunity, and proved to be a promising platform for the induction of immunity against viral surface glycoprotein targets.TRIAL REGISTRATIONClinicalTrials.gov NCT01443936 and NCT01806909.FUNDINGIntramural and Extramural Research Programs of the NIAID, NIH (U19 AI109946) and the Centers of Excellence for Influenza Research and Surveillance (CEIRS), NIAID, NIH (contract HHSN272201400008C).

[Application of digital technique aided occlusal rehabilitation in implant-supported fixed prosthesis of fully edentulous patients].

Objective: To evaluate the clinical outcomes of digital technique-aided occlusal rehabilitation based on implant-supported fixed prostheses (ISFP), and to provide some information for clinical application of digital technique. Methods: Retrospectively reviewed the cases which had used neuromuscular system and condylar movement tracing device to reconstruct occlusion in one or double jaw fully edentulous ISFP from January, 2013 to January, 2020. A total of 6 eligible patients were enrolled in the present study with 56 implants and 8 ISFP, including 4 male patients and 2 female patients, aged from 43 to 74 years. The clinical outcomes were evaluated in four aspects, including implant survival rate, implants success rate, marginal bone loss and the occurrence of prosthesis complications. Results: The follow-up time was (4.0±2.2) years (1-7 years). The implant survival rate was 100% (56/56) and the implant success rate was 98% (55/56), with an average missal and distal marginal bone loss of (0.04±0.11) mm/year. Veneer chipping occurred at incisal edge of 2 adjacent incisors in only one prosthesis 3 years after rehabilitation. Conclusions: Combination of digital techniques of neuromuscular system and condylar movement tracing device to assist occlusal rehabilitation based on ISFP showed a high implant success rate. The complication seldom happened. Long and stable occlusion has been observed. The clinical outcomes were favorable.

Pegylated interferon alpha-2a versus standard interferon alpha-2a for treatment-naive dialysis patients with chronic hepatitis C: a randomised study.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is prevalent in dialysis patients, and standard interferon monotherapy is the current standard of care for such patients. AIM: To investigate whether pegylated interferon has a better therapeutic efficacy and safety profile than standard interferon in dialysis patients with chronic hepatitis C. METHODS: 50 such patients were randomly assigned to receive either pegylated interferon alpha-2a 135 microg subcutaneously once per week or standard interferon alpha-2a 3 million units subcutaneously thrice per week for 24 weeks. The primary efficacy and safety end points were sustained virological response (SVR) by intention-to-treat analysis and treatment-related withdrawal rate during the study. RESULTS: In univariate analysis, patients receiving pegylated interferon alpha-2a tended to have a higher sustained virological response (SVR) than those receiving standard interferon alpha-2a (48% vs 20%, p = 0.07). By using multivariate analysis, treatment with pegylated interferon alpha-2a (p = 0.02) and pretreatment HCV RNA level <800 000 IU/ml (p = 0.007) were independently predictive of an SVR. All patients failing to achieve a rapid virological response (RVR) could not achieve an SVR. In addition, patients receiving pegylated interferon alpha-2a had a significantly lower treatment-related withdrawal rate than those receiving standard interferon alpha-2a (0% vs 20%, p = 0.04). CONCLUSIONS: Pegylated interferon alpha-2a once weekly provides more effective and safer therapy than standard interferon alpha-2a thrice weekly for treatment-naive dialysis patients with chronic hepatitis C.

Prevention of Postdental Procedure Bacteremia: A Network Meta-analysis.

Postdental procedure bacteremia is common and troublesome. The comparative efficacy of multiple prophylactic interventions is unclear. We compared the efficacy of interventions for the prevention of postdental procedure bacteremia. We conducted a review of ClinicalKey, Cochrane CENTRAL, Embase, ProQuest, PubMed, ScienceDirect, Web of Science, and ClinicalTrials.gov from inception to December 4, 2018. Randomized controlled trials that evaluated prophylactic interventions for the prevention of postdental procedure bacteremia were eligible. The primary outcome was the incidence of postdental procedure bacteremia. A total of 24 trials were included with 2,147 participants. Our network meta-analysis demonstrated that intravenous administration of 1,000/200 mg of amoxicillin/clavulanate provided the least incidence of postdental procedure bacteremia among all the prophylactic interventions (odds ratio = 0.03, 95% CI = 0.00 to 0.63) as compared with the placebo/controls. Oral 3 g of amoxicillin had the least incidence of postdental procedure bacteremia among all oral or topical forms of prophylactic interventions (odds ratio = 0.10, 95% CI = 0.02 to 0.44) as compared with the placebo/controls. No serious adverse events, such as anaphylactic shock, mortality, and the development of antibiotic-resistant bacteria, were reported. None of the included subjects were of high risk of infectious endocarditis. Our network meta-analysis demonstrates that intravenous amoxicillin/clavulanate and oral amoxicillin might be the best prophylactic interventions in preventing postdental procedure bacteremia among all the oral/topical forms of interventions for the overall populations.

Combination of Pluronic/Vitamin E TPGS as a potential inhibitor of drug precipitation.

In this study, we screened surfactants and their combinations at low concentrations as potentially potent inhibitors of drug precipitation in an aqueous medium. Nine surfactants (including Pluronic F127, Pluronic F108, and Pluronic F68) were evaluated at concentrations below their critical micelle concentrations (CMCs) using an in vitro precipitation assay. A model compound used in this study showed a sharp pH-dependent solubility profile and was much more soluble in simulated gastric fluid (SGF) (pH 1.2) than in simulated intestinal fluid (SIF) (pH 7.4). The compound was first dissolved in SGF with each surfactant, and the solutions were dispensed into the wells of a 96-well microtiter plate by a TECAN robot and diluted 10-fold with SIF. After a preset incubation time at room temperature, the solutions were filtrated through a 96-well filter plate, and the compound concentration in the filtrate was measured using an HPLC method. At concentrations below their CMCs, Pluronic F127 and Pluronic F108, but not Pluronic F68, inhibited the compound precipitation in SIF. Combinations of Pluronic F127 or Pluronic F108 with Vitamin E TPGS showed significantly stronger inhibition than the individual surfactants, indicating synergistic effects on inhibition of drug precipitation.

Evaluation of drug precipitation of solubility-enhancing liquid formulations using milligram quantities of a new molecular entity (NME).

A precipitation screening method using a 96-well microtiter plate was developed to evaluate in vitro drug precipitation kinetics of liquid formulations for poorly water-soluble compounds, using milligram quantities of compounds and milliliter volumes of biorelevant media. By using this method we identified three formulations showing distinct in vitro precipitation kinetics (fast, slow, and no precipitation) for a model new molecular entity (JNJ-25894934). The in vitro precipitation profiles in simulated intestinal fluid (SIF), fasted state simulated intestinal fluid (FaSSIF), and fed state simulated intestinal fluid (FeSSIF) were compared with those measured by a USP dissolution method, and with in vivo absorption at the fasted and fed states in canine pharmacokinetic (PK) studies. The precipitation kinetics of all three formulations in the initial hours measured by the screening method correlated to those determined by the USP method (R(2) = 0.96). The PK results showed that the fast-precipitation formulation had the lowest bioavailability. However, a similar bioavailability was observed for the slow- and no-precipitation formulations. The oral bioavailability of JNJ-25894934 at the fed state was also significantly higher than that at the fasted state for all three formulations (p < 0.05). In addition, the in vitro precipitation profiles in FeSSIF correlated better with in vivo absorption than those in SIF and FaSSIF.

[Imaging analysis of temporomandibular joint anatomy changes after intraoral condylectomy combined with orthognathic surgery].

OBJECTIVE: To quantitatively analyze the changes of facial symmetry and temporomandibular joint structure at different periods after intraoral condylectomy combined with orthognathic surgery, and to evaluate the long-term stability after the operation. METHODS: Spiral CT data of 10 cases treated by intraoral condylectomy combined with orthognathic surgery were collected, and then reconstructed by ProPlan software. Mark points were drawn on the 3D-images reconstructed immediately after the operation, and 6 months and 12 months after the operation. The measurements parameters included condylar axis angle in three dimensions, condylar-glenoid relative position and condylar facial morphology related indicators. The results were statistically analyzed by the consistency test and the variance of repeated measurement data. RESULTS: The facial asymmetry of the patients was corrected after operation, the height of the affected mandibular ascending ramus(T1: [67.81±6.95]mm, T2: [64.49±6.24]mm, T3: [63.05±7.07]mm)as well as the degree of pogonion deviation decreased(T1: [2.79±4.93]mm, T2: [0.37±4.20]mm, T3: [0.33 ± 3.97]mm)(P<0.05). But the tilt angle of the occlusion plane and the degree of mandibular height asymmetry had no significant difference between all the post-operative periods(P>0.05). The post-operative 3D changes of the position and shape of the resected and its contralateral condylar showed that the bilateral condylar axis angle in the horizontal plane gradually grew after operation(affected condyle: 71.95° ± 7.47°, 74.73°±8.44°, 76.56°±5.22°; control condyle: 72.60°±5.56°, 76.00°±5.30°, 77.19°±6.20° and had significant difference between all the post-operative periods)(P<0.05), the condyle moved slowly upward on both sides(superior space on the affected side: [8.78±4.38]mm, [4.11±2.49]mm, [3.27±1.96]mm; on the control side: [3.63±1.49]mm, [2.52±1.19]mm, [2.38±1.11]mm)(P<0.05), and moved inward only on the affected side(P< 0.05). All the above changes slowed down over time, and the disc-condyle-fossa relative position tended to be stable over time as well. The condyle diameter on the inside-outside direction gradually decreased on the affected side(T1: [14.98±2.39]mm, T2: [14.04±2.68]mm, T3: [13.74±2.89]mm)(P<0.05), and the surface morphology of the resected condyle was similar to the normal side. There were also some condylar surface morphological changes on the control side, but no statistical significance was found between different periods after the peration(P>0.05). CONCLUSIONS: The intraoral condylectomy combined with orthognathic surgery can eliminate condylar lesions effectively and correct the facial asymmetry caused by condylar benign tumor and hyperplasia. The facial symmetry can be maintained well after the operation, and the post-operative condylar morphology changes tended to be stable six months after the operation.

Alterations by norepinephrine of cardiac sympathetic nerve terminal function and myocardial beta-adrenergic receptor sensitivity in the ferret: normalization by antioxidant vitamins.

BACKGROUND: Chronic excessive norepinephrine (NE) causes cardiac sympathetic nerve terminal abnormalities, myocardial beta-adrenergic receptor downregulation, and beta-adrenergic subsensitivity. The present study was carried out to determine whether these changes could be prevented by antioxidants. METHODS AND RESULTS: Ferrets were administered either NE (1.33 mg/d) or vehicle by use of subcutaneous pellets for 4 weeks. Animals were simultaneously assigned to receive either antioxidant vitamins (beta-carotene, ascorbic acid, and alpha-tocopherol) or placebo pellets. NE increased plasma NE 4- to 5-fold but had no effect on heart rate, heart weight, arterial pressure, or left ventricular systolic function. However, myocardial NE uptake activity and NE uptake-1 site density were reduced, as well as cardiac neuronal NE, tyrosine hydroxylase, and neuropeptide Y. In addition, there was a decrease in myocardial beta-adrenergic receptor density with a selective decrease of the beta(1)-receptor subtype, reduction of the high-affinity site for isoproterenol, decreased basal adenylyl cyclase activity, and the adenylyl cyclase responses to isoproterenol, Gpp(NH)p, and forskolin. All of these changes were prevented by antioxidant vitamins. The effects of NE on myocardial beta-adrenergic receptor density, NE uptake-1 carrier site density, and neuronal NE were also prevented by superoxide dismutase or Trolox C. CONCLUSIONS: The toxic effects of NE on the sympathetic nerve terminals are mediated via the formation of NE-derived oxygen free radicals. Preservation of the neuronal NE reuptake mechanism is functionally important, because the antioxidants also prevented myocardial beta-adrenergic receptor downregulation and postreceptor abnormalities. Thus, antioxidant therapy may be beneficial in heart failure, in which cardiac NE release is increased.

Effect of long-term exposure to fluoride in drinking water on risks of bone fractures.

Findings on the risk of bone fractures associated with long-term fluoride exposure from drinking water have been contradictory. The purpose of this study was to determine the prevalence of bone fracture, including hip fracture, in six Chinese populations with water fluoride concentrations ranging from 0.25 to 7.97 parts per million (ppm). A total of 8266 male and female subjects > or =50 years of age were enrolled. Parameters evaluated included fluoride exposure, prevalence of bone fractures, demographics, medical history, physical activity, cigarette smoking, and alcohol consumption. The results confirmed that drinking water was the only major source of fluoride exposure in the study populations. A U-shaped pattern was detected for the relationship between the prevalence of bone fracture and water fluoride level. The prevalence of overall bone fracture was lowest in the population of 1.00-1.06 ppm fluoride in drinking water, which was significantly lower (p < 0.05) than that of the groups exposed to water fluoride levels > or =4.32 and < or =0.34 ppm. The prevalence of hip fractures was highest in the group with the highest water fluoride (4.32-7.97 ppm). The value is significantly higher than the population with 1.00-1.06 ppm water fluoride, which had the lowest prevalence rate. It is concluded that long-term fluoride exposure from drinking water containing > or =4.32 ppm increases the risk of overall fractures as well as hip fractures. Water fluoride levels at 1.00-1.06 ppm decrease the risk of overall fractures relative to negligible fluoride in water; however, there does not appear to be similar protective benefits for the risk of hip fractures.

Regulation of hormone(PTH and PGE1)-stimulated adenylate cyclase by renal cytosolic factors.

Cytosolic factors in a 50--75% (NH4)2SO4 fraction of the 105 000 x g supernatant of the renal cortex modulated adenylate cyclase activity in membrane preparations enriched in renal tubular cell basal--lateral membranes. The crude factor preparation had no effect on basal activity but it contained components that augmented the stimulated of the enzyme by NaF, parathyroid hormone (PTH), prostaglandin E1 (PGE1), and inhibited the activation of the enzyme by GMP--PNP. The factor(s) potentiating the stimulation by the hormones was partially purified (13-fold) by DEAE-cellulose and Sephadex G-75 chromatography. During purification, the component(s) that increased hormone-stimulated adenylate cyclase was separated from those affecting the activity in the presence of NaF and GMP--PNP. The factor(s) enhanced the PTH- and PGE1-stimulated enzyme at all concentrations of hormone, suggesting that the affinity for the hormone was not affected. The factor(s) was heat-stable. Partial proteolysis with chymotrypsin greatly reduced the ability of the factor(s) to enhance hormonal responsive adenylate cyclase. However, the factor(s) was resistant to trypsin digestion. The effect of the factor was not due to GTP, nor was GTP necessary for its action. Ca2+ was not needed for the enhancing activity of the factor(s). These findings suggest the presence in the cytosol of the kidney cortex of a protein(s) that regulates the response of renal adenylate cyclase to hormones. The relationship between this kidney cytosolic factor and those reported in other tissues remains to be established.

Health effects of indoor fluoride pollution from coal burning in China.

The combustion of high fluoride-content coal as an energy resource for heating, cooking, and food drying is a major exhaust emission source of suspended particulate matter and fluoride. High concentrations of these pollutants have been observed in indoor air of coal-burning families in some rural areas in China. Because airborne fluoride has serious toxicological properties, fluoride pollution in indoor air and the prevalence of fluorosis have been analyzed in a fluorosis area and a healthy nonfluorosis area in China and in a rural area in Japan. For human health, fluoride in indoor air has not only been directly inhaled by residents but also has been absorbed in stored food such as corn, chilies, and potatoes. In the fluorosis area in China, concentrations of urinary fluoride in the residents have been much higher than in the nonfluorosis area in China and in the rural area in Japan. In the fluorosis area, almost all elementary and junior high school students 10-15 years of age had dental fluorosis. Osteosclerosis in the skeletal fluorosis patients was very serious. Urinary deoxypyridinoline in rural residents in China was much higher than in rural residents in Japan. Data suggest that bone resorption was extremely stimulated in the residents in China and that fluoride may stimulate both bone resorption and bone formation. Because indoor fluoride from combustion of coal is easily absorbed in stored food and because food consumption is a main source of fluoride exposure, it is necessary to reduce airborne fluoride and food contamination to prevent serious fluorosis in China.