[Show abstract][Hide abstract] ABSTRACT: High temperature hyperthermia (HTH) treatment has previously been demonstrated to suppress tumor growth in a tumor-bearing rat model. In the present study, the effects of HTH therapy for the treatment of spontaneous tumors in canines was evaluated. In case 1, an 18-year-old female Papillon presented with a right forelimb rhabdomyosarcoma. Case 2 was a 13-year-old male English Cocker Spaniel with a right external auditory canal ceruminous adenocarcinoma and case 3 was a 14-year-old male Golden Retriever that exhibited a perianal gland adenocarcinoma, which surrounded the anus. HTH treatment was performed in all three cases for 10 min at 45-65°C with or without the inhalation of isoflurane. In case 1, the tumor disappeared four weeks following HTH treatment. In case 2, the tumor volume had decreased by day 21, and in case 3, HTH was performed three times and the tumor disappeared following the third procedure. HTH is considered to be a simple procedure with no severe side effects. Consequently, this treatment modality is hypothesized to become a useful alternative therapy for superficial tumors in companion animals.
[Show abstract][Hide abstract] ABSTRACT: The current study evaluated the anti-tumor activities of N-acetyl-d-glucosamine oligomer (NACOS) and glucosamine oligomer (COS) after their oral administration in a tumor (colon 26)-bearing mouse model. Compared to the control group, NACOS and COS groups showed significantly suppressed tumor growth, and apparent, marked apoptosis in tumor tissues. Furthermore, serum interleukin-12p70 and interferon-γ levels significantly increased in the NACOS and COS groups compared to the corresponding levels in the control group. Collectively, the results indicate the oral administration of NACOS and COS could enhance innate immunity. Results of experiments in Myd-88 knockout mice revealed that the apparent effects were related to both Myd-88-dependent and Myd-88-independent pathways. The data indicated that oral administration of NACOS and COS produced anti-tumor effects through the induction of apoptosis and stimulation of the immune system, which suggests that NACOS and COS are candidate anti-tumor functional foods.
[Show abstract][Hide abstract] ABSTRACT: Previous studies have suggested that ozonated water is safe and possesses antibacterial effects for treatment of experimental peritonitis rats. In this study, we evaluated the anti-inflammatory effects of ozonated water that was intraperitoneally injected into an experimental inflammatory mouse model. The concentrations of dissolved ozone decreased constantly and lineally, while the half-life of dissolved ozone was 36.8±2.7 min (27°C). The 10-ppm ozonated water was injected intraperitoneally into mice with lipopolysaccharide (LPS)-induced acute inflammation. The results showed that the intraperitoneal injection of ozonated water decreased the levels of tumor necrosis factor-α (TNF-α) and increased the activity of superoxide dismutase (SOD). The results suggest that ozonated water has anti-inflammatory properties and is a potential therapeutic option for acute inflammation.
[Show abstract][Hide abstract] ABSTRACT: Cryoablation is a minimally invasive cancer treatment. In this study, the effects of cryoablation on normal rabbit bone were evaluated using imaging and histopathological examinations. Cryoablation was performed using a Cryo-Hit (Galil Medical, Yokneam, Israel). Under anesthesia, one cryoablation needle was inserted at the center of the femur (day 0). To create an ice ball (2 × 3 cm), two 10-min freeze cycles were performed, separated by a 5-min thaw cycle. During cryoablation, changes in the bone and regional tissue were monitored using magnetic resonance imaging (MRI). MRI scans, computed tomography (CT) scans, and collections from the femur (for histopathological evaluation) were performed on days 7, 14, 28, and 56. In terms of the all rabbits' general conditions, we did not observe lameness, decreased appetite, or any other side effects during the experimental periods. Histopathological evaluations of the femur were performed using hematoxylin and eosin staining. MRI indicated inflammation around the ice ball on day 7. Subsequently, the area of inflammation gradually decreased from days 14 to 56. In the histopathological examination, necrosis of bone marrow cells and endosteum were observed from days 7 to 56. No regeneration of bone marrow cells was observed during the experimental period. On the other hand, cryoablation did not influence osteoblasts. Furthermore, there was no pathologic fracture during the experimental period. Our results suggest that cryoablation does not induce severe adverse effects on normal bone, and therefore has potential as a therapeutic option for bone tumors, including metastatic tumors to bone.
[Show abstract][Hide abstract] ABSTRACT: This report describes a dog with a clinical stage III oral malignant melanoma that was treated with complementary alternative medicine (CAM). The CAM included high temperature hyperthermia, dendritic cell therapy and lupeol injections. Surgery, radiation and chemotherapy were not performed. Two months after the start of treatment, the tumor disappeared and after six months, the follow-up examinations revealed no recurrence or metastasis of the tumor. Quality of life (QOL) of the dog was maintained; therefore, the application of CAM may be an effective treatment for canine oral malignant melanoma. The effective application of CAM has the potential to prolong life and maintain an excellent QOL for pets.
[Show abstract][Hide abstract] ABSTRACT: The present study examined the effects of onion peel tea (OPT) in a mouse model of high-fat-diet-induced obesity. BALB/c mice were fed a high-fat diet for three weeks, followed by a normal diet with or without OPT for 28 days. OPT suppressed the increases in body weight and level of epididymal fat tissue; it also significantly reduced the serum concentrations of total cholesterol on day 14 and those of glucose and leptin on day 28. The results indicate that OPT has anti-obesity effects in an experimental mouse model of high-fat-diet-induced obesity.
Experimental and therapeutic medicine 02/2014; 7(2):379-382. · 0.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chitins are highly crystalline structures that are predominantly found in crustacean shells. Alpha-chitin is composed of microfibers, which are made up of nanofibrils that are 2-5nm in diameter and 30nm in length and embedded in a protein matrix. Crystalline nanofibrils can also be prepared by acid treatment. We verified the effect of chitin nanofibrils (NF) and nanocrystals (NC) on skin using a three-dimensional skin culture model and Franz cells. The application of NF and NC to skin improved the epithelial granular layer and increased granular density. Furthermore, NF and NC application to the skin resulted in a lower production of TGF-β compared to that of the control group. NF and NC might have protective effects to skin. Therefore, their potential use as components of skin-protective formulations merits consideration.
[Show abstract][Hide abstract] ABSTRACT: Water-soluble chitosan derivative-based nanoparticles (carboxymethyl chitosan-chitooligosaccharide nanoparticles (CMC-COS NP) and sulphated chitosan-chitooligosaccharide nanoparticles (SC-COS NP)) were prepared by the formation of polyelectrolyte complexes. SC-COS NP and CMC-COS NP both induced the proliferation of mouse fibroblasts, whereas they elicited dose-dependent inhibitory effects on the proliferation of both HeLa and mouse B16 melanoma cells. Injection of SC-COS NP and CMC-COS NP modulated serum Th cytokines and stimulated the proliferation of splenic lymphocytes (CD4+ and CD8+ T cells, CD19+ B cells and NK cells) in mice, indicating the ability of these particles to regulate both humoral and cell-mediated immune responses. These properties demonstrated their promising potential for application as biomedical materials.
Journal of Experimental Nanoscience 01/2014; 9(8). · 0.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Sixteen cases of malignant soft tissue sarcoma (STS) (10 canine and 6 feline) were treated with a novel triple therapy that combined photodynamic therapy, hyperthermia using indocyanine green with a broad-band light source, and local chemotherapy after surgical tumor resection. This triple therapy was designated photodynamic hyperthermal chemotherapy (PHCT). In all cases, the surgical margin was insufficient. In one feline case, PHCT was performed without surgical removal. PHCT was performed over an interval of 1 to 2 weeks and was repeated 3 to 21 times. No severe side effects, including severe skin burns, necrosis, or rupture of skin sutures, were observed in any of the animals. No recurrence was observed in 7 of 10 (70.0%) dogs and 3 of 6 (50.0%) cats over follow-up periods ranging from 286 to 1901 days. These results suggest that PHCT decreases the risk of recurrence. PHCT should therefore be considered an adjuvant therapy for STS in companion animal medicine.
[Show abstract][Hide abstract] ABSTRACT: We herein describe the establishment of single hepatic lesions of Echinococcus multilocularis in rats. A 3mm incision was made on the liver with a surgical knife, and one small round vesicle of E. multilocularis (between 1×1mm and <2×2mm in diameter) was transplanted into the incision and covered with absorbable hemostat gauze. The presence and growth of the transplanted vesicle was monitored for 12weeks using magnetic resonance imaging (MRI). Hepatic lesions, the metacestode of this parasite were confirmed in 12 of 17 infected rats (70.6%) by MRI and macroscopic examinations. The average size of the metacestodes with brood capsules at 12weeks after the experimental transplantation of a single vesicle was 6.1±2.5mm×4.4±1.5mm. The smallest size of the metacestodes detected by MRI was approximately 3×3mm. This new approach of establishing single hepatic metacestodes of E. multilocularis in experimental animals is expected to be useful for analyzing the immune-pathological mechanisms of hepatic AE.
[Show abstract][Hide abstract] ABSTRACT: Melanoma is the most aggressive type of skin cancer and it is procured from activated or genetically altered epidermal melanocytes. In the present study, the tumor-suppressive effects of systemic and local injections of lupeol, a triterpene extracted from Indian lettuce (Lactuca indica), in a melanoma-bearing mouse model were evaluated. Mice were injected once with lupeol or olive oil (solvent control) subcutaneously into the skin of the back or into the tumor tissue. Seven days after the injection, the tumor growth rates were calculated and the tumor tissues were collected. Immunohistochemical staining for Ki-67 and proliferating cell nuclear antigen (PCNA) were performed. The tumor growth rates in the lupeol-injected group were significantly decreased compared to those observed in the non-treated (NT) and solvent control groups. Lupeol also significantly decreased the areas positively stained for Ki-67 and PCNA in the tumor tissues compared to those in the NT and solvent control groups. The results of the present study demonstrated that systemic and local injections of lupeol suppress tumor growth and induce cell cycle arrest in a melanoma-bearing mouse model. These data suggest that lupeol may be effective as a novel therapeutic option for melanoma patients.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to evaluate the effects of cellulose nanofibers from Japanese pear (P-CNF) on acute IBD by using a mouse model of this disorder. Furthermore, using this mouse model, we compared the effects between P-CNF and cellulose nanofibers from wood (W-CNF).
P-CNF suppressed shortening of the colon length and improved the histological tissue injury in the mice. It also suppressed the activation of nuclear factor-kappa B and fibrosis of the colon, as well as the myeloperoxidase activation of inflammatory cells such as leukocytes. On the other hand, W-CNF did not improve the histological tissue injury, or suppress shortening of the colon length, colon inflammation, and fibrosis in the mice. These results revealed that P-CNF has anti-inflammatory effects in the experimental IBD mouse model. Our results indicate that P-CNF could be a potential source of new dietary fiber for patients with IBD.
Bioactive Carbohydrates and Dietary Fibre. 01/2013;
[Show abstract][Hide abstract] ABSTRACT: The effects of pear vinegar (PV), which was specially brewed for enhanced galacturonic acid content, on the DSS-induced ulcerative colitis (UC) mouse model were evaluated. PV improved clinical symptoms, colon inflammation, and histological tissue injury in the DSS-induced acute UC mouse model. Moreover, PV suppressed inflammation due to acute UC by suppressing the myeloperoxidase (MPO)-mediated activation of inflammatory cells such as leukocytes and decreasing the serum concentration of IL-6. Our results demonstrated the protective action of PV in the DSS-induced acute UC mouse model. On the other hand, commercial apple vinegar did not show a protective effect in the DSS-induced acute UC mouse model. Our findings indicate that PV may act as a new functional food for inflammatory bowel disease patients.
Journal of Functional Foods. 01/2013; 5(1):516–523.
[Show abstract][Hide abstract] ABSTRACT: In this study, we investigated the suppressive effects of cellulose nanofibers made from adlay (A-CNF) and seaweed (S-CNF) on colon inflammation using the mouse model of inflammatory bowel disease (IBD). A-CNF and S-CNF suppressed shortening of the colon length and improved the histological tissue injury in mice. A-CNF and S-CNF also suppressed the activation of nuclear factor-kappa B in the colon. Furthermore, A-CNF and S-CNF suppressed the myeloperoxidase activities of inflammatory cells such as leukocytes. On the other hand, cellulose nanofibers made from wood did not improve the histological tissue injury or suppress the shortening of the colon length and colon inflammation in mice. These results revealed that A-CNF and S-CNF have suppressive effects on colon inflammation in an experimental IBD mouse model. Furthermore, our results indicate that A-CNF and S-CNF may be a potential source of dietary fiber for patients with IBD.
Bioactive Carbohydrates and Dietary Fibre. 01/2013; 2(1):65–72.
[Show abstract][Hide abstract] ABSTRACT: We investigated the effect of fucoidan, a sulfated polysaccharide, on acceleration of healing of experimental cartilage injury in a rabbit model. An injured cartilage model was surgically created by introduction of three holes, one in the articular cartilage of the medial trochlea and two in the trochlear sulcus of the distal femur. Rabbits in three experimental groups (F groups) were orally administered fucoidan of seven different molecular weights (8, 50, 146, 239, 330, 400, or 1000 kD) for 3 weeks by screening. Control (C group) rabbits were provided water ad libitum. After the experimental period, macroscopic examination showed that the degree of filling in the fucoidan group was higher than that in the C group. Histologically, the holes were filled by collagen fiber and fibroblasts in the C group, and by chondroblasts and fibroblasts in the F groups. Image analysis of Alcian blue- and safranin O-stained F-group specimens showed increased production of glycosaminoglycans (GAGs) and proteoglycans (PGs), respectively. Some injured holes were well repaired both macroscopically and microscopically and were filled with cartilage tissues; cartilage matrices such as PGs and GAGs were produced in groups F 50, F 146, and F 239. Thus, fucoidan administration enhanced morphologically healing of cartilage injury.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to elucidate the relationship between plasma free amino acid (PFAA) levels and the clinical stages of mammary gland tumors (MGT) in dogs. PFAA levels in canines with malignant mammary tumors were decreased compared to those of healthy animals. The levels of aspartate and ornithine, in the dogs with tumor metastasis were significantly decreased when compared to those of dogs that did not have metastases. Results of this study indicate that PFAA levels could be a risk factor or biomarker for canine MGT metastasis.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to investigate the correlations of severity of osteoarthritis (OA) and serum biomarkers including keratan sulfate (KS), hyaluronic acid (HA), and chondroitin sulfate (CS) 846 epitope. We also investigated the effect of glucosamine and fish collagen peptide (FCP) on OA. OA was induced in 12 rabbits (12 weeks of age) by anterior cruciate ligament transection (ACLT). After the surgery, the rabbits were orally administered FCP (F group), glucosamine (G group), or FCP and glucosamine (FG group) for 4 weeks. The control group was provided water ad libitum (C group). Blood was collected before surgery (pre-ACLT) and before euthanasia (post-ACLT) for serum marker measurement. Biomarker levels were measured by using commercial kits. We evaluated OA severity both macroscopically and histologically. Macroscopic evaluation showed mildly eroded condylar surfaces in the C group. Histological findings were significantly different from the FG and other groups. There were no significant differences between each group at post-ACLT in serum KS, HA and CS 846. Histological assessment and serum biomarker measurements performed at post- ACLT showed a significant correlation between HA concentration and OA severity. Variations in the CS 846 concentration at pre- and post-ACLT were significantly correlated with OA severity. Administration of glucosamine and FCP had chondroprotective effects in the ACLT model. Serum biomarker concentrations were significantly correlated with cartilage injury. Serum biomarker measurement would be useful for monitoring articular cartilage damage in the clinical setting.
Journal of Veterinary Medical Science 11/2012; · 0.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We evaluated the anti-tumor activities of the oral administration of fucoidan extracted from Cladosiphon okamuranus using a tumor (colon 26)-bearing mouse model. The materials used included low-molecular-weight fucoidan (LMWF: 6.5-40 kDa), intermediate-molecular-weight fucoidan (IMWF: 110-138 kDa) and high-molecular-weight fucoidan (HMWF: 300-330 kDa). The IMWF group showed significantly suppressed tumor growth. The LMWF and HMWF groups showed significantly increased survival times compared with that observed in the control group (mice fed a fucoidan-free diet). The median survival times in the control, LMWF, IMWF and HMWF groups were 23, 46, 40 and 43 days, respectively. It was also found that oral administration of fucoidan increased the population of natural killer cells in the spleen. Furthermore, from the results of the experiment using Myd-88 knockout mice, it was found that these effects are related to gut immunity. These results suggest that fucoidan is a candidate anti-tumor functional food.
[Show abstract][Hide abstract] ABSTRACT: We investigated the correlation of plasma amino acid concentrations as well as the effects of glucosamine and fish collagen peptide (FCP) on osteoarthritis (OA). OA was induced according to the rabbit anterior cruciate ligament transection model. After surgery, the rabbits were orally administered with FCP (F group), glucosamine (G group), or both (FG group) for 4 weeks. The control group (C group) was not administered any. Blood was collected before the surgery (pre-ACLT) and before euthanasia (post-ACLT). Changes in the alanine, threonine, and methionine concentrations were significant between pre- and post-ACLT. The correlation between the histological assessment and arginine concentration at post-ACLT was significant. These findings indicate the measurement of plasma amino acids is useful for evaluation of the efficacy of intervention of OA.
Journal of Veterinary Medical Science 09/2012; · 0.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We evaluated the anti-inflammatory and anti-fibrosis effects of α-chitin nanofibrils in a mouse model of dextran sulfate sodium (DSS)-induced acute ulcerative colitis (UC). α-Chitin nanofibrils decreased positive areas of nuclear factor-κB staining in the colon tissue (7.2 ± 0.5%/fields in the α-chitin nanofibrils group vs. 10.7 ± 0.9%/fields in the control group; p < 0.05). α-Chitin nanofibrils also decreased serum monocyte chemotactic protein-1 concentration in DSS-induced acute UC (24.1 ± 7.8 pg/ml in the α-chitin nanofibrils group vs. 53.5 ± 3.1 pg/ml in the control group; p < 0.05). Moreover, α-chitin nanofibrils suppressed the increased positive areas of Masson's trichrome staining in colon tissue (6.8 ± 0.6%/fields in the α-chitin nanofibrils group vs. 10.1 ± 0.7%/fields in the control group; p < 0.05). On the other hand, α-chitin powder suspension did not show these effects in DSS-induced acute UC mice model. Our results indicated that α-chitin nanofibrils have the anti-inflammatory effect via suppressing NF-κB activation and the anti-fibrosis effects in DSS-induced acute UC mice model.