Evaluation of Immunosuppressive Therapy Use for Tracheal Transplantation with Trachea-Mimetic Bellows Scaffolds in a Rabbit Model.

The objective of this study was to evaluate the use of immunosuppressive therapy with high-dose cyclosporine, high-dose azathioprine, and a combination of low-dose cyclosporine and azathioprine after tracheal reconstruction by using a trachea-mimetic graft of polycaprolactone (PCL) bellows-type scaffold in a rabbit model. Twenty-four healthy New Zealand white rabbits were used in the study. All underwent circumferential tracheal replacement using tissue-engineered tracheal graft, prepared from PCL bellows scaffold reinforced with silicone ring, collagen hydrogel, and human turbinate mesenchymal stromal cell (hTMSC) sheets. The control group (Group 1) received no medication. The three experimental groups were given daily cyclosporine intramuscular doses of 10 mg/kg (Group 2), azathioprine oral doses of 5 mg/kg (Group 3), and azathioprine oral doses of 2.5 mg/kg plus cyclosporine intramuscular doses of 5 mg/kg (Group 4) for 4 weeks or until death. Group 1 had longer survival times compared to Group 2 or Group 3. Each group except for Group 1 experienced decreases in amount of nutrition and weight loss. In addition, compared with the other groups, Group 2 had significantly increased serum interleukin-2 and interferon-γ levels 7 days after transplantation. The results of this study showed that the administration of cyclosporine and/or azathioprine after tracheal transplantation had no beneficial effects. Furthermore, the administration of cyclosporine had side effects, including extreme weight loss, respiratory distress, and diarrhea. Therefore, cyclosporine and azathioprine avoidance may be recommended for tracheal reconstruction using a native trachea-mimetic graft of PCL bellows-type scaffold in a rabbit model.

Neuropharmacological Potential of Gastrodia elata Blume and Its Components.

Research has been conducted in various fields in an attempt to develop new therapeutic agents for incurable neurodegenerative diseases. Gastrodia elata Blume (GE), a traditional herbal medicine, has been used in neurological disorders as an anticonvulsant, analgesic, and sedative medication. Several neurodegenerative models are characterized by oxidative stress and inflammation in the brain, which lead to cell death via multiple extracellular and intracellular signaling pathways. The blockade of certain signaling cascades may represent a compensatory therapy for injured brain tissue. Antioxidative and anti-inflammatory compounds isolated from natural resources have been investigated, as have various synthetic chemicals. Specifically, GE rhizome extract and its components have been shown to protect neuronal cells and recover brain function in various preclinical brain injury models by inhibiting oxidative stress and inflammatory responses. The present review discusses the neuroprotective potential of GE and its components and the related mechanisms; we also provide possible preventive and therapeutic strategies for neurodegenerative disorders using herbal resources.

Bone regeneration of hydroxyapatite/alumina bilayered scaffold with 3 mm passage-like medullary canal in canine tibia model.

The aim of this study was to evaluate the bone regeneration of hydroxyapatite (HA)/alumina bilayered scaffold with a 3 mm passage-like medullary canal in a beagle tibia model. A porous HA/alumina scaffold was fabricated using a polymeric template-coating technique. HA/alumina scaffold dimensions were 10 mm in outer diameter, 20 mm in length, and with either a 3 mm passage or no passage. A 20 mm segmental defect was induced using an oscillating saw through the diaphysis of the beagle tibia. The defects of six beagles were filled with HA/alumina bilayered scaffolds with a 3 mm passage or without. The segmental defect was fixated using one bone plate and six screws. Bone regeneration within the HA/alumina scaffolds was observed at eight weeks after implantation. The evaluation of bone regeneration within the scaffolds after implantation in a beagle tibia was performed using radiography, computerized tomography (CT), micro-CT, and fluorescence microscopy. New bone successfully formed in the tibia defects treated with 3 mm passage HA/alumina scaffolds compared to without-passage HA/alumina scaffolds. It was concluded that the HA/alumina bilayered scaffold with 3 mm passage-like medullary canal was instrumental in inducing host-scaffold engraftment of the defect as well as distributing the newly formed bone throughout the scaffold at 8 weeks after implantation.

Osteogenesis induced by a bone forming peptide from the prodomain region of BMP-7.

Osteoporosis is a reduction in skeletal mass due to an imbalance between bone formation and bone resorption. Many researchers have tried to develop adjuvants as specific suppressors of bone resorption and stimulators of bone formation for therapeutic purposes in patients with osteoporosis. Therefore, specific stimulators on bone formation are one of therapeutic significance in the treatment of osteoporosis. Until now, the regulation of bone generation has been the focus of bone morphogenetic protein-7 (BMP-7) investigation from mature form. However, new peptides from immature form which has osteogenic activity has not been reported and developments of these proteins are still remained. In this study, we found a new peptide sequence, called bone forming peptide-1 (BFP-1) and have more high activities of osteogenic differentiation compared with BMP-7. BFP-1-treated multipotent bone marrow stromal stem cells (MBSCs) induced the expression levels and activity of alkaline phosphatase (ALP). Moreover, BFP-1 enhanced the levels of CD44, CD47 and CD51 expression as well as increased Ca(2+) content in MBSCs. In current study, radiography at 8 weeks revealed that BFP-1 pretreated-MBSC transplanted animals had strongly increased bone formation compared to that in the BMP-7 pretreated MBSC transplanted animals. Our finding indicates a new insight into peptides from the immature region of BMP-7 can also be useful in the development of adjuvant therapies for bone-related diseases.

Therapeutic effect of korean red ginseng extract on infertility caused by polycystic ovaries.

Polycystic ovarian syndrome (PCOS) is a very common endocrine disorder in women of reproductive age. Nerve growth factor (NGF) may be involved in the pathogenesis of PCOS. In this study, we investigated the effect of Korean red ginseng extract (KRGE) on the ovarian morphology and NGF expression in an estradiol valerate (EV)-induced rat model. Polycystic ovaries were induced by a single intramuscular injection of estadiol valerate (4 mg, dissolved in sesame oil) in adult cycling rats. KRGE was administered orally (200 mg/kg body weight/day) for 60 consecutive days, beginning 60 days after the induction. Ovarian morphology was almost normalized and NGF was normalized in the EV+KRGE group. KRGE lowered the high numbers of antral follicles and increased the number of corpora lutea in the polycystic ovaries. The results are consistent with a beneficial effect of KRGE in the treatment of PCOS.

Therapeutic effect of total ginseng saponin on skin wound healing.

In this study, we investigated the effects of total ginseng saponin (TGS) on the cutaneous wound healing process using histological analysis. A total of 24 ICR mice, 5-weeks-old, were used for all in vivo experiments. Mice were divided into control and TGS-treated groups and four equidistant 1-cm full-thickness dorsal incisional wounds were created. The wounds were extracted at days 1, 3, 5, and 7 post-injury for histomorphometrical analysis including wound area and contracture measurements, keratinocyte migration rate, and calculation of infiltrating inflammatory cells. The results showed that the wound area was smaller and keratinocyte migration rate was higher in the TGS-treated group than that of the control group from days 3 to 7. Inflammatory cells in the TGS-treated group at days 1 and 3 were reduced compared to the control group. Wound contraction in the TGS-treated group was greater than in the control group on days 3 to 5, and collagen deposition in the TGS-treated group was higher than in the control group during wound healing. The results indicate a beneficial effect of TGS when used to treat skin wounds.

Effect of Korean red ginseng extract in a steroid-induced polycystic ovary murine model.

Experimental induction of polycystic ovary (PCO) in rodent resembling some aspects of human PCO syndrome was produced using the long-acting compound estradiol valerate (EV). Our previous study on the role of Korean red ginseng total saponins in a steroid-induced PCO rat model demonstrated that electro-acupuncture modulates nerve growth factor (NGF) concentration in the ovaries. In fact, the involvement of a neurogenic component in the pathology of PCO-related ovarian dysfunction is preceded by an increase in sympathetic outflow to the ovaries. In the present study, we tested the hypothesis that Korean red ginseng extract (KRGE) administration modulates sympathetic nerve activity in PCO-induced rats. This was done by analyzing NGF protein and NGF mRNA expression involved in the pathophysiological process underlying steroid-induced PCO. EV injection resulted in significantly higher ovarian NGF protein and NGF mRNA expression in PCO-induced rats compared to control rats, and PCO ovaries were counteracted by KRGE administration with significantly lower expression of NGF protein and NGF mRNA compared to EV treated ovaries. These results indicate that EV modulates the neurotrophic state of the ovaries, which may be a component of the pathological process by which EV induces cyst formation and anovulation in rodents.

Inhibitory effect of whole bee venom in adjuvant-induced arthritis.

The aim of this study was to assess the inhibitory effect of whole bee venom (BV) on adjuvant-induced arthritis in the rat. Rats were divided into pre-apitherapy, post-apitherapy and control experimental groups. The pre-apitherapy group was subcutaneously stung with a honeybee (Apis mellifera L.) and the control group was subcutaneously injected with 0.1 ml of physiological saline solution one day prior to complete Freund's adjuvant (CFA) injection. The post-apitherapy group was subcutaneously stung with a honeybee on day 14 after CFA injection. When arthritis had developed in the rat, the post-apitherapy group was subcutaneously administered whole BV every other day for a further 14 days. Clinical signs, hematological values and radioglogical features were observed during the entire experimental period. In the pre-apitherapy group, the development of inflammatory edema and polyarthritis was inhibited. Significant differences in lameness score, hind paw edema volume and radiological features were observed between control and pre-apitherapy rats. White blood cell counts indicated that the degree of leucocytosis was significantly different between the pre-apitherapy and control groups (p < 0.01). Inflammatory edema, polyarthritis and bone change into the right hind paw were effectively inhibited in pre-apitherapy rats during the two-week period post-CFA injection. In conclusion, whole BV was found to inhibit arthritic inflammation and bone changes in the rat. This may be an alternative treatment for arthritis in humans.

Effect of low-level laser therapy on osteoarthropathy in rabbit.

The aim of this study was to determine whether low-level laser therapy (LLLT) aided the recovery of damaged articular cartilage in joints with artificially induced osteoarthropathy (OA). OA was induced by injecting hydrogen peroxide (H2O2) into the articular spaces of both knees in rabbits, twice a week for 4 weeks. The induction of OA and the effect of LLLT were evaluated by biochemical, radiological and histopathological analysis. Superoxide dismutase (SOD) activity increased about 40% in the OA group, as compared to the controls. Although SOD activity in the OA group was not significantly different from the 2-week groups, it was significantly different from the 4-week control and treatment groups. There was also a significant difference between the 4-week control and treatment groups. Simple radiographs and three-dimensional computed tomographs (3D CT) did not show detectable arthropathy in the OA group, nor any particular changes in the 2-week groups. In contrast, distinct erosions were seen in the distal articular cartilage of the femur, with irregularity of the articular surface, in the 4-week control group, while the erosions were reduced and arthropathy improved slightly in the 4-week treatment group. Grossly, erosions formed on the articular surface in the OA group. In comparison, severe erosions damaged the articular cartilage in the 4-week control group, but not in the 2-week control and treatment groups. Regeneration of articular cartilage was seen in gross observations in the 4-week treatment group. Histopathologically, there was slight irregularity of the articular surface and necrosis in the OA group, and serious cartilage damage, despite slight chondrocyte regeneration, in the 4-week control group. Conversely, the 4-week treatment group showed chondrocyte replacement, with sometimes close to normal articular cartilage on the articular surface. These results suggest that LLLT was effective in the treatment of chemically-induced OA.

The effects of alpha-viniferin on adjuvant-induced arthritis in rats.

This study was performed to assess the efficacy of alpha-viniferin (Carex humilis Leyss) on adjuvant-induced arthritis in rats. Adjuvant arthritis was induced by a single subcutaneous injection of 0.1 ml complete Freund's adjuvant (CFA) containing 7.5 mg Mycobacterium butyricum suspended in 1 ml sterile paraffin oil into the right hind paw. Forty female Sprague-Dawley rats were injected. Righting reflex was uniformly lost and considered to be the initial point of arthritis development on day 7 after CFA injection. Rats were divided into four groups, and upon development of arthritis, tested groups were orally administered 3 or 10 mg/kg alpha-viniferin or 10 mg/kg ketoprofen every day for 14 days. The control group was orally administered 2 ml of physiological saline solution. Bone mineral density (BMD), radiological changes and edematous volumes were measured for 35 days. Alpha-viniferin suppressed the development of inflammatory edema, and inhibited the bone destruction, noted with a decrease in BMD (p < 0.05). Hind paw edema volume, BMD and radiological changes did not differ significantly in the ketoprofen and alpha-viniferin groups during the entire study period. In conclusion, alpha-viniferin suppressed arthritic inflammation and bony change in rats.

Effect of apitherapy in piglets with preweaning diarrhea.

This study was designed to examine the therapeutic effect of honeybee (Apis mellifera L.) venom in piglets with bacterial diarrhea Comparison between bee venom- and drug-treated groups was our main concern in the present study. Preweaning piglets were assigned to treated and non-treated control groups. In the treated group, 47 piglets were acupunctured with the worker honeybee once a day for three consecutive days. Two acupoints, GV-1 (Jiao-chao) and ST-25 (Hai-men), were selected for apitherapy. In the control group, 44 piglets were intramuscularly injected with a standard dose of a known antibacterial drug, colistin sulfate (300,000 IU/kg of body weight), and an antidiarrheal drug (berberine, 2 ml/kg) once a day for three consecutive days. At post-treatment, 90.9% of the control piglets and 93.6% of piglets in the treated group recovered from bacterial diarrhea. Bee acupuncture therapy did not show any side effects such as allergy, intoxication, hemorrhage or infection. It is concluded that bee venom therapy was effective in controlling bacterial diarrhea in preweaning piglets.

Effect of bee venom treatment in sows with oligogalactic syndrome postpartum.

The objective of this study was to determine the clinico-therapeutic effect of worker honeybee venom in sows with oligogalactic syndrome postpartum. Comparison between bee venom- and drug-treated groups was our main concern in the present study. Sows after parturition were assigned to bee venom- and drug-treated groups, respectively. In the bee venom-treated group, 22 sows were bee-acupunctured once a day for 3 consecutive days. Honeybees (Apis mellifera L.) forbee acupuncture were about 15 days old after metamorphosis. Live bees were used to sting the acupoints known as yang-ming (ST-18, 1.5 cm lateral to the base of the last two pairs of teats) and jiao-chao (GV- , at the indentation between the base of tail and the anus). In the drug-treated group, 20 sows were intramuscularly injected with a standard dose of penicillin G (400,000 IU/head) once a day for 3 consecutive days. On post-treatment day 4, 85.0% of the drug-treated group and 90.9% of the bee venom-treated group recovered from oligogalactic syndrome postpartum. The result suggested that apitherapy using worker honeybee is an effective treatment for sows with oligogalactic syndrome postpartum.

The effect of whole bee venom on arthritis.

This study was performed to assess the clincotherapeutic effect of whole venom of honeybee (Apis mellifera) in adjuvant-induced arthritic rat. Ninety Sprague-Dawley male rats were injected with complete Freund's adjuvant (CFA). Adjuvant arthritis was produced by a single subcutaneous injection of I mg Mycobacterium butyricum suspended in 0.1 ml paraffin oil into the right hind paw. Righting reflex was uniformly lost and considered to be the point of arthritis development on day 14 after CFA injection. The experiments were divided into three groups. When arthritis was developed in the rat, tested groups were administered with prednisolone (10 mg/kg, p.o.) or honeybee venom (one bee, s.c.) every other day for another 14 days. Control group was injected with 0.1 ml of physiological saline solution subcutaneously. Clinical and hematological values with histopathological findings were observed during the drug administration. In treatment groups, the development of inflammatory edema and polyarthritis was suppressed. No significant differences of hind paw edema volume and lameness score between prednisolone and honeybee venom groups were observed during treatment. White blood cell counts of control group showed leucocytosis that was significantly different from the two treatment groups (p < 0.01). Erosions of articular cartilage and inflammatory cell infiltrations into interphalangeal joint were effectively suppressed in treated groups. In conclusion, whole honeybee venom was found to suppress arthritic inflammation in the rat. This may be an alternative treatment of arthritic agony in humans.