• Journal of Pharmaceutical Investigation
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• v.39 no.2
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• pp.97-106
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• 2009

Although lovastatin (LS) is widely used in the treatment of hypercholesterolemia, its bioavailability is known to be around 5%. This study was aimed to increase the solubility and dissolution-permeation rates of LS using solid dispersions (SDs) with bile salts. The solubilities of LS in water, aqueous bile salt solutions and non-aqueous vehicles were determined, and effects of bile salts on the cellulose or duodenal permeation of LS from SDs were evaluated using a horizontal permeation system. SDs were prepared at various ratios of LS to carriers, such as sodium deoxycholate (SDC), sodium glycocholate (SGC) and/or 2-hydroxypropyl-$\beta$-cyclodextrin (HPCD). The addition of bile salts (25 mM) in water increased markedly the solubility of LS by the micellar solubilization. Some non-aqueous vehicles were effective in solubilizing LS. From differential scanning calorimetric studies, it was found that the crystallinity of LS in SDs disappeared, indicating a formation of amorphous state. The SDs showed markedly enhanced dissolution compared with those of their physical mixtures (PMs) and drug alone. In the dissolution-permeation studies using a cellulose membrane, the donor and receptor solutions were maintained as a sink condition using pH 7.0 phosphate buffer containing 0.05% sodium lauryl sulfate (SLS). The flux of LS alone was nearly same as that of LS-SDC-HPCD (1:3:6) PM. However, the flux of LS-SDC-HPCD (1:3:6) SD slightly increased compared with drug alone and PM, suggesting that entrapment of LS in micelles does not significantly hinder the permeation across cellulose membrane. In the dissolution-duodenal permeation studies using a LS-HPCD-SDC (1:3:6) SD, the addition of various bile salts in donor solutions (25 mM) enhanced the permeation of LS markedly, and the fluxes were found to be $0.69{\pm}0.41$, $0.87{\pm}0.51$, $0.84{\pm}0.46$, $0.47{\pm}0.17$ and $0.68{\pm}0.32{\mu}g/cm^2/hr$ for sodium cholate (SC), SDC, SGC, sodium taurodeoxycholate (STDC) and sodium taurocholate (STC), respectively. The stepwise increase of donor SGC concentration increased the flux dose-dependently. From the relationship of donor SGC concentration and flux, the concentration of SGC initiating the permeation across the duodenal mucosa was calculated to be 11.1 mM, which is nearly same as the critical micelle concentration (CMC, 11.6 mM) of SGC. However, with no addition of bile salts and below CMC, the permeation was very limited and irratic, indicating that LS itself is very poor permeable. Higher protions of bile salt in SD such as LS-SDC or LS-SGC (1 : 49 and 1 : 69) showed highly promoted fluxes. In conclusion, SD systems with bile salts, which may form their micelles in intestinal fluids, might be a promising means for providing enhanced dissolution and intestinal permeation of practically insoluble and non-absorbable LS.

• Clinics in Shoulder and Elbow
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• v.2 no.1
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• pp.21-27
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• 1999

Purpose : The purpose of this study was to evaluate the functional outcomes of one-part fracture of the greater tuberosity that had been treated either by a conservative treatment or an operative approach. Materials and Method: Eighteen shoulders in 18 patients who had an one-part fracture of the greater tuberosity of the proximal humerus were managed, and the average follow-up period was 4 years and 10 months (range, 1 year to 8 years 6 months). Results: According to Neer's criteria for evaluation of results, in the group of 13 patients managed nonoperatively, the results were good or excellent in ten patients, fair in one, and poor in two. In the group managed operatively, the results were excellent in all five patients. Conclusion: If the displacement of the fragment is more than 5mm in young active patients, and more than 3mm especially in athletes and heavy laborers involved in overhead activity, the fragment should be mobilized, repaired and fixed into its original bed or a little bit inferolaterally with multiple heavy non-absorbable sutures, tension band technique, or cancellous screws and washers. We would suggest that the patients showing one-part fracture of the greater tuberosity of the proximal humerus should be evaluated individually.

• The Journal of Internal Korean Medicine
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• v.33 no.1
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• pp.26-38
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• 2012

Objectives : The aim of this study was to investigate the effect of partial pyloric obstruction on body weight, gastric juice, gastric surface area and gastric edema in normal intact and/or vagotomized rats. Methods : Partial pyloric obstruction was performed by wrapping a non-absorbable rubber ring (D:6 mm, W:4 mm, T:1 mm) around the 1st portion of the duodenum. Vagotomy was performed by resecting the branches around the esophagogastric junction. Pre-post body weight differential, fasting gastric juice volume, gastric surface area and gastric edema were measured at 8 weeks and 20 weeks. For the effect of pyloric reperfusion the rubber ring was removed after 8 weeks and then an additional 12 weeks of observation was performed to the end of the 20-week experimental period. Results : In the initial 8 weeks observation, the effect of pylorus obstruction and/or vagotomy was significantly remarkable in the pylorus obstructed and vagotomized group; slowdown of weight gain, increase of fasting gastric juice volume, dilatation of gastric surface area and severe gastric edema were shown. In the remaining 12 weeks observation, the effect of reperfusion was significantly remarkable in the ring-removed antral dilated group; recovery of weight gain, decrease of gastric surface area and decrease of gastric edema were shown. However, gastric juice volume was not significantly different from the other group. Conclusions : Partial pyloric obstruction plays a aggravating role and the vagus nerve plays a protective role in body weight, gastric juice, gastric surface area, and gastric edema. Furthermore, pyloric valve dysfunction as an aggravating factor strengthened in defect of the vagus nerve. These results suggest that patients with both functional pyloric outlet obstruction and hypofunction of vagus nerve need to be diagnosed in good time and treated properly.

• Journal of Chest Surgery
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• v.7 no.2
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• pp.163-168
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• 1974

Five cases of traumatic diaphragmatic hernia were repaired in the Department of Thoracic Surgery, Seoul National University Hospital, during the period from 1967 to 1974. The first case, a 14-year aid girl, was diagnosed as diaphragmatic hernia during laparotomy because of jejunal perforation 3 days after traffic accident. Herniated stomach, transverse colon, spleen and left lobe of the liver were repositioned and the diaphragmatic rupture on left posterolateral portion was repaired with two layers of nonabsorbable sutures by transthoracic approach. The second case, a 26-year old man,was diagnosed immediately after traffic accident at a local clinic and transferred to this hospital 24 hours later. Herniated stomach, transverse colon and jejunum were repositioned amd diaphragmatic rupture,about 9 cm in length,from the posterolat.edge to the base of pericardium was sutured in two layers. The third case, a 26-year old man who had stab wound on the left lower lateral chest two years ago,was admitted with sudden abdominal pain and vomiting. Upper gastrointestinal series with barium meal revealed diaphragmatic hernia. The herniated stomach and transverse colon through the defect,about 3.5cm in diameter, at anterolateral portion on the left side,were repositioned and repaired with two layers of nonabsorbable sutures. The forth case, a 26-year old man, sustained blunt trauma to the chest by a roller and was transferred to the emergency room complaining of dyspnea 40 minutes after the accident. The diaphragmatic rupture extended from left midaxillary line to contralateral anterior axillary line,about 20cm long, at anterior portion of diaphragm, which was repaired with two layers, of nonabsorbable sutures. The fifth case, a 4-year old girl, had two separate diaphragmatic ruptures on both sides, which were caused by traffic accident. Immediate upper gastrointestinal series after injury showed herniated stomach, colon and spleen into left Chest cavity. Another small rupture with anterior edge of right lobe of the liver in chest cavity was noted. These were repaired with non-absorbable sutures via thoracotomy.

• Journal of Korean Neurosurgical Society
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• v.58 no.5
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• pp.494-498
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• 2015

Objective : To describe a novel spinous process-splitting hemilaminoplasty technique for the surgical treatment of intradural and posterior epidural lesions that promotes physiological restoration. Methods : The spinous process was split, the area of the facet lamina junction was drilled, and en bloc hemilaminectomy was then performed. After removing intradural and posterior epidural lesions, we fitted the previously en bloc-removed bone to the pre-surgery same shape, and held it in place with non-absorbable sutures. Surgery was performed on 16 laminas from a total of nine patients between 2011 and 2014. Bony union of the reconstructed lamina was assessed using computed tomography (CT) at 6 months after surgery. Results : Spinous process-slitting hemilaminoplasty was performed for intradural extramedullary tumors in eight patients and for ossification of the ligament flavum in one patient. Because we were able to visualize the margin of the ipsilateral and contralateral dura, we were able to secure space for removal of the lesion and closure of the dura. None of the cases showed spinal deformity or other complications. Bone fusion and maintenance of the spinal canal were found to be perfect on CT scans. Conclusion : The spinous process-splitting hemilaminoplasty technique presented here was successful in creating sufficient space to remove intradural and posterior epidural lesions and to close the dura. Furthermore, we were able to maintain the physiological barrier and integrity after surgery because the posterior musculature and bone structures were restored.

• Journal of Ginseng Research
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• v.37 no.1
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• pp.108-116
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• 2013

For the improvement of ginsenoside bioavailability, the ginsenosides of fermented red ginseng by Phellinus linteus (FRG) were examined with respect to bioavailability and physiological activity. The polyphenol content of FRG ($19.14{\pm}0.50$ mg/g) was significantly higher (p<0.05) compared with that of non-fermented red ginseng (NFRG, $11.31{\pm}1.15$ mg/g). The antioxidant activities in FRG, such as 2,2'-diphenyl-1-picrylhydrazyl, 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid, and ferric reducing antioxidant power, were significantly higher (p<0.05) than those in NFRG. The HPLC analysis results showed that the FRG had a high level of ginsenoside metabolites. The total ginsenoside contents in NFRG and FRG were $41.65{\pm}1.53$ mg/g and $50.12{\pm}1.43$ mg/g, respectively. However, FRG had a significantly higher content ($33.90{\pm}0.97$ mg/g) of ginsenoside metabolites (Rg3, Rg5, Rk1, compound K, Rh1, F2, and Rg2) compared with NFRG ($14.75{\pm}0.46$ mg/g). The skin permeability of FRG was higher than that of NFRG using Franz diffusion cell models. In particular, after 3 h, the skin permeability of FRG was significantly higher (p<0.05) than that of NFRG. Using a rat everted intestinal sac model, FRG showed a high transport level compared with NFRG after 1 h. FRG had dramatically improved bioavailability compared with NFRG as indicated by skin permeation and intestinal permeability. The significantly greater bioavailability of FRG may have been due to the transformation of its ginsenosides by fermentation to more easily absorbable forms (ginsenoside metabolites).

• Preventive Nutrition and Food Science
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• v.14 no.3
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• pp.201-207
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• 2009

In an effort to improve ginsenoside bioavailability, the ginsenosides of fermented red ginseng were examined with respect to bioavailability and physiological activity. The results showed that the fermented red ginseng (FRG) had a high level of ginsenoside metabolites. The total ginsenoside contents in non-fermented red ginseng (NFRG) and FRG were 35715.2 ${\mu}g$/mL and 34822.9 ${\mu}g$/mL, respectively. However, RFG had a higher content (14914.3 ${\mu}g$/mL) of ginsenoside metabolites (Rg3, Rg5, Rk1, CK, Rh1, F2, and Rg2) compared to NFRG (5697.9 ${\mu}g$/mL). The skin permeability of RFG was higher than that of NFRG using Franz diffusion cells. Particularly, after 5 hr, the skin permeability of RFG was significantly (p<0.05) higher than that of NFRG. Using everted instestinal sacs of rats, RFG showed a high transport level (10.3 mg of polyphenols/g sac) compared to NFRG (6.67 of mg of polyphenols/g sac) after 1 hr. After oral administration of NFRG and FRG to rats, serum concentrations were determined by HPLC. Peak concentrations of Rk1, Rh1, Rc, and Rg5 were approximately 1.64, 2.35, 1.13, and 1.25-fold higher, respectively, for FRG than for NFRG. Furthermore, Rk1, Rh1, and Rg5 increased more rapidly in the blood by the oral administration of FRG versus NFRG. FRG had dramatically improved bioavailability compared to NFRG as indicated by skin permeation, intestinal permeability, and ginsenoside levels in the blood. The significantly greater bioavailability of FRG may have been due to the transformation of its ginsenosides by fermentation to more easily absorbable forms (ginsenoside metabolites).

• Journal of Veterinary Clinics
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• v.32 no.4
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• pp.356-358
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• 2015

When severely large corneal perforation occurs, penetrating keratoplasty is a treatment of choice alternative to enucleation. A twelve-year-old male Shih Tzu was referred with perforated corneal ulcer secondary to keratoconjunctivitis sicca (KCS). Perforated cornea was directly sutured using 10-0 non-absorbable suture material, and rotational conjunctival flap was performed. However, re-perforation of cornea by wound dehiscence was observed at 1 month after operation. The yellowish lens escaped outside the orbit during corneal re-perforation, the diagnosis was re-perforated corneal ulcer, moderate corneal edema, moderate KCS (STT; 6 mm) and endophthalmitis caused by escaped lens outside orbit. Accordingly, penetrating keratoplasty (PK) and evisceration through corneal recipient site and intrascleral silicone ball prosthesis were carried out as the planned treatment, and resulted in good cosmetic improvement compared to enucliation. However, exposure of silicone ball occurred at the 9 months after the surgery due to the irritation of implant, thus enucleation was performed. In perforated large corneal ulcer with severe intraocular damage, evisceration with silicone ball insertion with PK would be alternative treatment choice to improve the cosmetic appearance.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.21 no.3
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• pp.257-265
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• 1999

To investigate the sequential changes in microvascular architecture and osseous regeneration during the bony healing after an application of the guided tissue regeneration method, we made artificial defects measuring $0.7cm{\times}0.3cm$ in size on femoral bones of rats measuring about 200gm and applied non-absorbable TEFE membrane at experimental sites but not at control sites. Then we observed the sequential changes and correlations between new vacuolation and bony regeneration using microvascular corrosion cast method and routine light microscopic observation at 1, 2 and 3 weeks after operation, respectively. The results showed that there were close relationships between regeneration of microvasculature and bone. In early phase, the invasion of granulation tissue at control sites delayed bony regeneration, however, in later phase, there was no remarkable differences in bony regeneration between control and experimental sites. The placement of barrier also affected in revascularization of regenerating bony defects. This is, the experimental sites showed parallel arranged nutritional vessels along long axis with well developed retiform plexus whereas the control revealed vertical invasion of microvasculature from outside of marrow space through bony defects which was also rearrange with time into parallel pattern with a vertical plexus but lesser organized than that of experimental sites. These findings suggest that the reconstruction of regenerating vasculature within the marrow cavity only may be sufficient and/or more be efficient in regeneration of bony defects.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.33 no.2
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• pp.112-119
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• 2011

Purpose: Collagen membranes are used extensively as bioabsorbable barriers in guided bone regeneration. However, collagen has different effects on tissue restoration depending on the type, structure, degree of cross-linking and chemical treatment. The purpose of this study was to evaluate the inflammatory reaction, bone formation, and degradation of dehydrothermal treated porcine type I atelocollagen (CollaGuide$^{(R)}$) compared to of the non-crosslinked porcine type I, III collagen (BioGide$^{(R)}$) and the glutaldehyde cross-linked bovine type I collagen (BioMend$^{(R)}$) in surgically created bone defects in rat mandible. Methods: Bone defect model was based upon 3 mm sized full-thickness transcortical bone defects in the mandibular ramus of Sprague-Dawley rats. The defects were covered bucolingually with CollaGuide$^{(R)}$, BioMend$^{(R)}$, or BioGide$^{(R)}$ (n=12). For control, the defects were not covered by any membrane. Lymphocyte, multinucleated giant cell infiltration, bone formation over the defect area and membrane absorption were evaluated at 4 weeks postimplantation. For comparison of the membrane effect over the bone augmentation, rats received a bone graft plus different covering of membrane. A $3{\times}4$ mm sized block graft was harvested from the mandibular angle and was laid and stabilized with a microscrew on the naturally existing curvature of mandibular inferior border. After 10 weeks postimplantation, same histologic analysis were done. Results: In the defect model at 4 weeks post-implantation, the amount of new bone formed in defects was similar for all types of membrane. Bio-Gide$^{(R)}$ membranes induced significantly greater inflammatory response and membrane resorption than other two membranes; characterized by lymphocytes and multinucleated giant cells. At 10 weeks postoperatively, all membranes were completely resorbed. Conclusion: Dehydrotheramal treated cross-linked collagen was safe and effective in guiding bone regeneration in alveolar ridge defects and bone augmentation in rats, similar to BioGide$^{(R)}$ and BioMend$^{(R)}$, thus, could be clinically useful.