• Journal of Pharmaceutical Investigation
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• v.27 no.4
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• pp.303-311
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• 1997

Proliposomal patch of clenbuterol, ${\beta}_2-agonist$ bronchodilator, was prepared and its feasibility as a novel transdermal drug delivery system was examined. Proliposomal granules containing clenbuterol was prepared by a standard method using sorbitol and lecithin with (Rx 2) or without cholesterol (Rx 1). The porous structure of sorbitol in the proliposomes was maintained allowing tree flowability of the granules. Following contact with water, the granules were converted probably to liposomes almost completely within several minutes. It indicates that proliposomes may be hydrated, when they are applied on the skin under occlusive condition in vivo, by the sweat to form liposomes. Clenbuterol release from Rx 1 and Rx 2 proliposomes to pH 7.4 isotonic phospate buffer (PBS) across cellulose membrane (mol. wt. cut-off of 12000-14000) was retarded significantly compared with that from the mixture of clenbuterol powder and blank proliposomes. Interestingly, proliposomes prepared with lecithin and cholesterol (i.e., Rx 2 proliposomes) showed much more retarded release of clenbuterol than proliposomes prepared only with lecithin (i.e.. Rx 1 proliposomes), indicating that clenbuterol release from proliposomes can be controlled by the addition of cholesterol to the proliposomes. Proliposomal patches were prepared using PVC film as an occlusive backing sheet, two sides adhesive tape (urethane, 1.45 mm thickness) as a reservoir for proliposome granules and Millipore MF-membrane (0.45 mm pore size) as a drug release-controlling membrane. Rx 1 or Rx 2 proliposomes containing 4.6 mg of clenbuterol were loaded into the reservoir of the patch. Clenbuterol release from the patches to pH 7.4 PBS was determined using USP paddle (50 rpm)-over-disc release method. Clenbuterol release from the proliposomal patches was much more retarded even than from a matrix type clenbuterol patch (Boehringer Ingelheim ltd). Being consistent with clenbuterol release from the proliposomal granules, the release from the patches was highly dependent on the presence of cholesterol in the proliposomes : Patches containing Rx 2 proliposomes showed several fold slower drug release than patches containing Rx 1 proliposomes. When the patch containing Rx 1 proliposomes was applied on to the back of a hair-removed rat, clenbuterol concentration in the rat blood was maintained during 6-72 hrs. Transdermal absorption of clenbuterol from the patch was accelerated when the patch was prehydrated with 50 ml of pH 7.4 PBS before topical application. Above results indicate that sustained transdermal delivery of clenbuterol is feasible using proliposomal patches if the cholesterol content and pore size of the release rate-controlling membrane of patches, for example, are appropriately controlled.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.5
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• pp.475-485
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• 2017

The present study aimed to explore the neuroprotective effect and possible mechanisms of rhGLP-1 (7-36) against transient ischemia/reperfusion injuries induced by middle cerebral artery occlusion (MCAO) in type 2 diabetic rats. First, diabetic rats were established by a combination of a high-fat diet and low-dose streptozotocin (STZ) (30 mg/kg, intraperitoneally). Second, they were subjected to MCAO for 2 h, then treated with rhGLP-1 (7-36) (10, 20, $40{\mu}g/kg$ i.p.) at the same time of reperfusion. In the following 3 days, they were injected with rhGLP-1 (7-36) at the same dose and route for three times each day. After 72 h, hypoglycemic effects were assessed by blood glucose changes, and neuroprotective effects were evaluated by neurological deficits, infarct volume and histomorphology. Mechanisms were investigated by detecting the distribution and expression of the nuclear factor erythroid-derived factor 2 related factor 2 (Nrf2) in ischemic brain tissue, the levels of phospho-PI3 kinase (PI3K)/PI3K ratio and heme-oxygenase-1 (HO-l), as well as the activities of superoxide dismutase (SOD) and the contents of malondialdehyde (MDA). Our results showed that rhGLP-1 (7-36) significantly reduced blood glucose and infarction volume, alleviated neurological deficits, enhanced the density of surviving neurons and vascular proliferation. The nuclear positive cells ratio and expression of Nrf2, the levels of P-PI3K/PI3K ratio and HO-l increased, the activities of SOD increased and the contents of MDA decreased. The current results indicated the protective effect of rhGLP-1 (7-36) in diabetic rats following MCAO/R that may be concerned with reducing blood glucose, up-regulating expression of Nrf2/HO-1 and increasing the activities of SOD.

• Journal of Dental Rehabilitation and Applied Science
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• v.28 no.3
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• pp.253-268
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• 2012

Full-mouth reconstruction of a patient using dental implants is a challenge if there is vertical and horizontal bone resorption, since this includes the gingival area and restricts the position of the implants. however, hard- and soft-tissue grafting may allow the implants to be placed into the desired position. Although it is possible to regenerate lost tissues, an alternative is to use fixed detachable prostheses that restore the function and the esthetics of the gingiva and teeth. Various material combinations including metal/acrylic, metal/ceramic, and zirconia/ceramic have been used for constructing this type of restoration. Other problems include wear, separation or fracture of the resin teeth from the metal/acrylic prosthesis, chipping or fracture of porcelain from the metal/ceramic or zirconia/ceramic prosthesis, and fracture of the framework in some free-end prostheses. With virtually unbreakable, chip-proof, life-like nature, monolithic zirconia frameworks can prospectively replace other framework materials. This clinical report describes the restoration of a patient with complete fixed detachable maxillary and mandibular prostheses made of monolithic zirconia with dental implants. The occluding surfaces were made of monolithic zirconia, to decrease the risk of chipping or fracture. The prostheses were esthetically pleasing, and no clinical complications have been reported after two years.

• Journal of Dental Rehabilitation and Applied Science
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• v.28 no.3
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• pp.269-276
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• 2012

Many researches have been published about the numerous factors related to the chewing ability of implant prosthesis. Most respective studies have concluded that the chewing ability of implant prosthesis is mostly fine compared to other type of prosthesis. However, some patients are not satisfied with their chewing ability of implant prosthesis. Therefore the neurologic factor, one of the factors related to dissatisfaction of chewing ability was reviewed in this study to understand the mechanism of action of mastication. Data was searched using the keywords; 'implant chewing ability, masticatory ability' in Pubmed database and reviewed. Definitions of chewing ability, factors of chewing ability are reviewed and the neurologic factor, one of the factors influencing on chewing ability, is reviewed. Mechanoreceptor of Periodontal ligament(PDL) is providing the mastication information to brainstem. Due to the absence of mechanoreceptions of PDL in implant, masticatory ability is decreased especially when chewing hard food. Masticatory muscles and mechanoreceptor in TMD may compensate the lack of mechanoreceptor of PDL in implants. Furthermore sensitivity of nerve fiber around peri-implant tissues may support the mechanoreception and sensory reaction in the implant mastication. However, further studies should be conducted to prove the relationships between neurologic factors and mastication.

• Journal of Dental Rehabilitation and Applied Science
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• v.30 no.3
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• pp.215-222
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• 2014

Purpose: The aim of this study was to investigate differences between the morphology of the mandibular symphysis and four facial skeletal types. Materials and Methods: 40 cone-beam computed tomographies were selected and classified in to 4 groups according to their vertical and anterior-posterior skeletal patterns. The bone volume ($mm^3$) of the symphysis, the cross sectional area corresponding to the 4 mandibular incisors' axis: the cross sectional area of total bone ($mm^2$), the area of the cancellous bone ($mm^2$) and the thickness (mm) of labial and lingual alveolar bone at 2 mm, 3 mm under the cemento-enamel junction (CEJ) were measured. General linear model (GLM), Kruskal-Wallis test and Tukey honestly significant difference (HSD) test were subsequently used for statistical analysis. Results: The lingual cortical bone thickness of the lateral incisors at 2, 3 mm under CEJ was greater in the Class I low angle group than the other 3 groups (P < 0.05). There were no statistically significant differences in the volume of the mandibular incisor bony support, cross-sectional area of total bone and cancellous bone at the mandibular incisor' axis. Conclusion: Patients in Class I, low angle group have a thicker lingual mandibular symphysis than Class I, high angle patients.

• Journal of Dental Rehabilitation and Applied Science
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• v.21 no.1
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• pp.1-14
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• 2005

The purpose of this study was to assess the loading distributing characteristics of implant prosthesis of internal connection system(ITI system) according to position and direction of load, under vertical and inclined loading using finite element analysis (FEA). The finite element model of a synOcta implant and a solid abutment with $8^{\circ}$ internal conical joint used by the ITI implant was constructed. The gold crown for mandibular first molar was made on solid abutment. Each three-dimensional finite element model was created with the physical properties of the implant and surrounding bone. This study simulated loads of 200N at the central fossa in a vertical direction (loading condition A), 200N at the outside point of the central fossa with resin filling into screw hole in a vertical direction (loading condition B), 200N at the centric cusp in a $15^{\circ}$ inward oblique direction (loading condition C), 200N at the in a $30^{\circ}$ inward oblique direction (loading condition D) or 200N at the centric cusp in a $30^{\circ}$ outward oblique direction (loading condition E) individually. Von Mises stresses were recorded and compared in the supporting bone, fixture, and abutment. The following results have been made based on this study: 1. Stresses were concentrated mainly at the ridge crest around implant under both vertical and oblique loading but stresses in the cancellous bone were low under both vertical and oblique loading. 2. Bending moments resulting from non-axial loading of dental implants caused stress concentrations on cortical bone. The magnitude of the stress was greater with the oblique loading than with the vertical loading. 3. An offset of the vertical occlusal force in the buccolingual direction relative to the implant axis gave rise to increased bending of the implant. So, the relative positions of the resultant line of force from occlusal contact and the center of rotation seems to be more important. 4. In this internal conical joint, vertical and oblique loads were resisted mainly by the implant-abutment joint at the screw level and by the implant collar. Conclusively, It seems to be more important that how long the distance is from center of rotation of the implant itself to the resultant line of force from occlusal contact (leverage). In a morse taper implant, vertical and oblique loads are resisted mainly by the implant-abutment joint at the screw level and by the implant collar. This type of implant-abutment connection can also distribute forces deeper within the implant and shield the retention screw from excessive loading. Lateral forces are transmitted directly to the walls of the implant and the implant abutment mating bevels, providing greater resistance to interface opening.

• Journal of Dental Rehabilitation and Applied Science
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• v.25 no.3
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• pp.255-265
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• 2009

Recently many studies have been published on application of immediate loaded implants. However, the immediate loading protocol has not been well documented. The purpose of the present study was to evaluate the stress distribution between bone-implant interfaces and the effect of implant length in the anterior maxilla using 3 dimensional finite element analyses. The diameter 4.0 mm threaded type implants with different length(8.5 mm, 10.0 mm, 11.5 mm, 13.0 mm, 15.0 mm) were used in this study. The bone quality of anterior maxillary bone block was assumed to D3 bone. Bone-implant interfaces of immediately loaded implant were constructed using a contact element for simulating the non osseointegration status. For simplification of all the processing procedures, all of the material assumed to be homogenous, isotropic, and linearly elastic. The 178 N of static force was applied on the middle of the palatoincisal line angle of the abutment with $120^{\circ}$ angle to the long axis of abutment. Maximum von Mises stress were concentrated on the labial cortical bone of the implant neck area, especially at the cortical-cancellous bone interfaces. Compared the different length, highest peak stress value was observed at the 8.5 mm implants and the results indicated a tendency towards favorable stress distribution on the bone, when the length was increased. Presence of cortical bone was very important to immediate loading, and it appears that implants of a length more than 13 mm are preferable for immediate loading at the anterior maxilla.

• Journal of Dental Rehabilitation and Applied Science
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• v.26 no.4
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• pp.389-403
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• 2010

Titanium and gold-alloy abutments have been used for a long-time in the clinical situations, but the use of zirconia abutments also increased. This study was designed to compare and evaluate the microgap differences according to types of abutment and dynamic loading. Titanium abutment, zirconia abutment and gold-alloy abutment (UCLA plastic) were connected into titanium implants of external hexagonal structure US II ${\phi}$ $3.75{\times}11.5$ mm (Osstem Co., Seoul, Korea) with the tightening torque of 30 Ncm. A sine type dynamic loading of 25-250 N and $30^{\circ}$ inclination from long axis was applied for $10^5$ times. Using the SEM both before and after the loadings, implant-abutment interfaces were analyzed on the labial, palatal, mesial and distal surface. The microgaps before and after the loading were compared, no statistically significant difference was observed caused by the dynamic loading on the labial, palatal, mesial or distal surface. Statistically significant difference was observed between UCLA and titanium group and between UCLA and zirconia group on both before and after the loading(p<0.05). No statistically significant difference was found between titanium and zirconia group. Loadings for $10^5$ times did not show significant effect to the microgaps between implants and abutments.

• International Journal of Oral Biology
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• v.33 no.4
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• pp.205-211
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• 2008

Gingival overgrowth can cause dental occlusion and seriously interfere with mastication, speech, and dental hygiene. It is observed in 25 to 81% of renal transplant patients treated with cyclosporine A (CsA). CsA-induced gingival overgrowth (CIGO) is caused by quantitative alteration of the extracellular matrix components, particularly collagen. However, the molecular mechanisms involved in the pathogenesis of CIGO remain poorly understood, despite intense clinical and laboratory investigations. The aim of the present work is to identify differentially expressed genes closely associated with CIGO. Human gingival fibroblasts were isolated by primary explant culture of gingival tissues from five healthy subjects (HGFs) and two patients with the CIGO (CIGO-HGFs). The proliferative activity of CsA-treated HGFs and CIGO-HGFs was examined using the MTT assay. The identification of differentially expressed genes in CsA-treated CIGO-HGF was performed by differential display reverse transcriptase-polymerase chain reaction (RT-PCR) followed by DNA sequencing. CsA significantly increased the proliferation of two HGFs and two CIGO-HGFs, whereas three HGFs were not affected. Seven genes, including the beta subunit of prolyl 4-hydroxylase (P4HB) and testican 1, were upregulated by CsA in a highly proliferative CIGO-HGF. The increased P4HB and testican-1 mRNA levels were confirmed in CsA-treated CIGO-HGFs by semiquantitative RT-PCR. Furthermore, CsA increased type I collagen mRNA levels and suppressed MMP-2 mRNA levels, which are regulated by P4HB and testican-1, respectively. These results suggest that CsA may induce gingival overgrowth through the upregulation of P4HB and testican-1, resulting in the accumulation of extracellular matrix components.

• The Journal of Korean Medicine
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• v.31 no.5
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• pp.82-89
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• 2010

Objectives: The aim of this study was to determine distribution patterns of TOAST subtypes of ischemic stroke patients admitted to oriental hospitals and to get a better understanding of present conditions in oriental medicine by comparing with the Korea stroke registry (KSR), the largest and representative data. Methods: Clinical data were collected from acute ischemic stoke patients. MRI studies including vascular images were performed in all cases. TOAST criteria were used to determine subtypes of ischemic stroke patients. According to the duration from disease onset to hospital admission time, patients were assigned to 3 groups (Group I0 to 3 d, Group II4 to 7 d, Group III8 to 28 d) and the distribution of TOAST subtypes were compared among these three groups. Results: We collected 514 sets of clinical data from 10 oriental hospitals between May 2007 and September 2009. Small vessel occlusion (SVO) subtype was the most common (57.62%), followed by large artery atherosclerosis (LAA, 29.98%). Compared with TOAST distribution of KSR, the proportion of ischemic stroke patients with SVO subtype was higher than that of KSR. On the other hand the proportion of patients with stroke of undetermined etiology (SUE) was lower. Distributions of SVO, LAA and cardioembolism (CE) in group were I 66.4%, 23.8% and 8.9%, respectively; those in group IIIwere 51.03%, 34.71% and 11.57%, respectively. Conclusions: In oriental hospitals, the proportion of ischemic stroke patients diagnosed as SVO type was higher than that of KSR. At early stage (from onset to 2 d) proportion of SVO was very high, however after 7 days from onset it decreased with concomitant increases in proportions of LAA and CE. These phenomena may be due to the facts that 1) at early stage emergency treatments are limited in oriental hospitals, 2) after early stage many patients prefer oriental treatments, including rehabilitation.