To clarify the role of stem cells in hepatocarcinogenesis, CD44 expression was investigated in mouse livers as well as embryonic cell lineages treated with diethylnitrosamine (DEN). Liver tumors induced by DEN were analyzed by immunohistochemisty for CD44. Liver tissues were sampled at 6, 24, and 48 hr after treatment with saline or DEN. Mouse embryonic stem cells (ESCs), hepatic progenitor cells (HPCs), and hepatocyte like cells (HCs), representing 0, 22, and 40 days of differentiation, respectively, were treated with DEN at four doses (0, 1, 5, and 15 mM, respectively) for 24 hr, after which CD44 expression levels were examined by relative quantitative real-time PCR. CD44 expression was weakly detected in tumor cells as well as in some hepatocytes surrounding the tumor cells. However, CD44 expression was not detected in liver tissue treated with DEN at early time points. The CD44 mRNA expression level was significantly different among cells treated with 5 mM DEN at day 22 (P<0.01) as well as 1, 5, and 15 mM DEN at day 40 (P<0.01) compared with control. Taken together, CD44 expression slightly increased in mouse DEN-induced tumors. Furthermore, expression of CD44 in embryonic cell lineages treated with various doses of DEN significantly differed among embryo stem cells and derived hepatic lineage cells. This suggests that CD44 expression may be modulated in the progeny of stem cells during their differentiation toward hepatocytes, and its expression may increase in the tumor stage but not during early carcinogenesis.

The purpose of this study was to identify the composition and organization of lingual tissues underlying the histo-structural change of developing tongue in Korean native goats by light microscopy (LM). Tongues of the fetuses on days 60, 90, 120 and neonate were examined for the morphological development. In the 60-day-old fetuses, the tongue tissues were differentiated into epithelium, lamina propria and muscle layer. Primordia of filiform, conical, lentiform, fungiform and vallate papillae appeared and rudiments of taste bud were observed in the epithelia of the primordia of the gustatory papillae. The dorsal surface of the lingual epithelia showed a weak PAS positive reaction. Collagenous fibers and small blood vessels were shown in the connective tissues. In the 90-day-old fetuses, Von Ebner’s glands were moderately PAS positive while the muscle fibers and connective tissue were strongly positive for PAS. The collagenous fibers increased and came to have a more complex arrangement in the tongue. The muscle fibers were spread out at various directions and developed in striated muscle bundles. In the 120-day-old fetuses, taste buds were observed in the epithelia of the gustatory papillae, and several well-developed tissues visible such as blood vessels, collagenous fibers, muscle fiber bundles and Von Ebner’s glands. In the neonates, many taste buds were found in a transverse section of the vallate papilla. The muscle layers, Von Ebner’s glands, collagenous fibers and blood vessels were more developed than those of the 120-day old fetuses. These findings indicate that goat tongues have a variety of different shapes during prenatal development.

Our previous research on sulfated polysaccharide purified from Ecklonia cava, a brown alga found in Jeju island, Korea, showed that sulfated polysaccharides modulate the apoptotic threshold of intestinal cells, thereby preventing intestinal damage caused by ionizing radiation. In this study, we investigated the ability of sulfated polysaccharide to augment restoration of small intestinal stem cells from γ-ray-induced damage. In our results, sulfated polysaccharide treatment increased the numbers of Ki-67-positive cells as well as inducible nitric oxide synthase (iNOS)-expressing cells in the small intestine compared with those of irradiated only mice. Meanwhile, exposure to irradiation increased the number of paneth cells, which are frequently associated with intestinal inflammation, whereas sulfated polysaccharide treatment reduced the number of paneth cells in the small intestinal crypt. Conclusively, our data suggest that reduction of iNOS-expressing cells and paneth cells in sulfated polysaccharide-treated mice contributes to the inhibition of radiation-induced intestinal inflammation.

This study was conducted in order to determine the functionality of mineral-rich salt with lower NaCl and higher mineral contents on blood pressure and lipid metabolism in Dahl salt-sensitive rats. A 1% salt solution was administered to five-week-old male Dahl rats– one normal and three salt groups (Purified salt, sun-dried salt, and bamboo salt) for 15 weeks. On the basis of the salt production process, the sun-dried group was classified into two subgroups: SS1 (2-year) and SS2 (>5-year) depending on the storage period of the mineral-rich salt. The relationships between salt intake and changes in blood pressure, serum lipids, and serum mineral concentrations were then examined. The results showed that intake of SS2, which is stored for five years, and BS (bamboo salt) resulted in continuous delay of the increase in blood pressure and inhibited angiotensin–converting enzyme (ACE) activity. In addition, a significant decrease in the triglyceride level in serum lipids of approximately 30% was observed in the SS2 group compared to the PS (purified salt) group. However, all salt intake groups showed an increase in total cholesterol levels compared to the normal group. The results demonstrate that intake of mineral-rich salt is beneficial for the human body and results in reduced blood pressure and triglyceride levels in serum lipids, however, conduct of more research will be needed in order to explore other functions.

In this study, characteristics and immuno-modulatory effects of Weissella cibaria JW15 isolated from Kimchi, traditional Korean fermented food, were examined for investigation of the capacity of potentially probiotic strains. We measured acid, bile, and heat tolerance, adhesive properties to intestinal epithelial cells, and inhibitory activity against pathogens. JW15 could survive at pH 3.0 for 2 hr, but not at pH 2.0. JW15 also showed tolerance to 0.3% oxgall bile salt, and heat tolerance at 70°C and 80°C for 5 min, respectively. Adhesive ability to Caco-2 cells was similar to that of Lactobacillus rhamnosus GG (LGG), a well-known commercial probiotic. JW15 exhibited antimicrobial activities to pathogenic bacteria such as Escherichia coli, Listeria monocytogenes, Staphylococcus aureus, and Salmonella enteritidis. The immuno-modulatory effects of JW15 were compared with those of LGG, a well-known immune enhancer. For analysis, production of nitric oxide (NO), NF-κB (Nuclear factor κB), Interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) was measured. The concentration of NO induced by JW15 was higher than that by LGG at low concentration (1 × 107 cfu/mL). Low and high (5 × 107 CFU/mL) concentration of JW15 induced statistically higher production of NF-κB, IL-1β, and TNF-α than that produced by LGG, respectively. In conclusion, Weissella cibaria JW15 had ability as a probiotic strain, including acid, bile, and heat tolerance, adhesive properties to intestinal epithelial cells, and inhibitory activity against pathogens. In addition, JW15 showed better immuno-modulatory effects than LGG when NO, NF-κB, IL-1β, and TNF-α were measured. According to these results, the characteristics and immunomodulating activity of Weissella cibaria JW15 are suitable for consideration as a potential probiotic.

Allergic disorders are exaggerated immune responses to foreign antigens, regardless of the mechanism, while atopic disorders are exaggerated IgE-mediated immune responses (type I hypersensitivity). Allergic dermatitis is a common pathological condition of skin in humans and dogs. Canine allergic dermatitis presents with clinical signs similar to those reported in humans, and its causes are complex; therefore, diagnostic tests and treatments may need to be adjusted for each patient. Dogs with allergic dermatitis can suffer from secondary infections, which must be considered and confirmed or excluded for successful treatment. In this report, 35 cases of canine allergic dermatitis diagnosed using variable methods, including histological and cytological examination, are described. Patients were treated with oral or topical medications (antimicrobials, anti-inflammatories, immune modulators, topical ointments, and medicated shampoos), and their diets and environmental surroundings were also modified. This report provides an analysis of the breed, gender, age of onset, clinical signs, diagnostic methods, and treatments for canine allergic dermatitis. The information on canine allergic dermatitis presented here could be helpful in the study of human cases because these two species often share living spaces, environments, and lifestyles more closely than other animals. However, previous reports have suggested that human and canine allergies differ in some features, such as involvement of histamine in induction of pruritus, and in histopathological characteristics such as cutaneous structures.

Inflammation mainly mediated by innate immune cells as the first line of host defense against pathogens is an acute response that limits tissue damage and eliminates pathogens in the body. In triggering inflammation, several pattern recognition receptors work together; membrane-associated Toll-like receptors, c-type lectin receptors, retinoic acid-inducible gene-like helicase receptors, absent in melanoma-like receptors, and cytosolic nucleotide-binding domain and leucine-rich repeat receptors. Among them, inflammasome is a newly trigger of inflammation in response to exogenous and endogenous stimuli and its activation leads to the assembly of multiprotein platforms composed of NLRP3 (NOD-like receptor family, pyrin domain containing 3), ASC (apoptosis associated speck-like protein containing a CARD), and procaspase 1. Thus, the activated inflammasome activates caspase 1, resulting in processing and secretion of interleukin (IL)-1β. Recent emerging data suggest that dysregulated metabolites, i.e., amyloids, ceramides, and cholesterol crystals, have been classified as inflammasome activators. In addition, IL-1β may play a critical role in the pathogenesis of chronic inflammation-induced disorders such as Alzheimer’s diseases, type 2 diabetes, and atheriosclerosis. This review introduces the basic concept of inflammasome activation and auto-inflammatory diseases. In addition, it discusses the updated signaling models of inflammasome activation that link metabolic dysfunction in order to outline future therapeutic approaches to inflammasome-mediating diseases.

Mesenchymal stem cell (MSC) based cell therapy has emerged as a promising therapeutic approach for treatment of several degenerative, infectious and non-infectious diseases. Numerous studies have demonstrated the remarkable immunosuppressive and antibacterial effects of MSCs both in vitro and in vivo, in animal models and in humans. However, the antibacterial effects of MSCs rely heavily on their paracrine factors rather than direct cell-to-cell contact and the effect is specific to disease and site of infection or injury. Furthermore, recent studies have demonstrated the double-edged sword effect of MSCs in bacterial infectious diseases. Despite their inherent potential for repair of damaged tissues, immunosuppression, and alleviation of various autoimmune as well as infectious diseases, MSCs also play a critical role in promoting persistent bacterial infection and disease progression. Therapeutic administration of MSCs successfully inhibited the bacterial growth and enhances survival by improved clearance of pathogenic bacteria in sepsis and pneumonic conditions. However, due to their abnormal transformation, they assist in long lasting survival and persistent infection of Mycobacterium tuberculosis (M. tuberculosis) and may also be responsible for progression of gastric cancer. This review focuses on recent advances that have broadened our understanding of MSC based therapy for bacterial diseases and provides new insight into the possible therapeutic targets of fatal bacterial diseases.

A-7-month-old, intact male Shih-Tzu dog was referred with facial dermatitis and stifle pain with 7 days duration. Erythema, hemorrhage, and crusted nodular lesions of the face, swollen eyelids, and otitis externa were observed. A painful response was noted on palpation of the right stifle joint. Impression smears and skin biopsies revealed pyogranulomatous inflammation consistent with canine juvenile cellulitis (CJC). Skin lesions and pain were greatly improved following immunosuppressive corticosteroid therapy. This report firstly describes clinical and histopatho- logical findings as well as treatment responses of CJC in a 7-month-old, domestic dog.

We would like to report a case of bovine lymphosarcoma. Parous cattle from a livestock farmhouse were examined for mutinodular masses in the abdominal cavity after slaughter. For clinical signs, animals presented mild leukemic signs but did not have viral or bacterial infection. Grossly, whitish to yellowish smooth masses similar to fat tissue were covered with a thin membrane. A multilobulated mass formed around the arteri, and there was a large quantity of reddish fluid on the cut surface. Histopathologically, a monomor- phic population of lymphocytes was observed along with small amounts of cytoplasm, round nuclei with coarsely granular chromatin, and numerous mitotic figures in the samples. In the tumor lesion, uniformly round cells had invaded with abundant neovascularization. Especially, the immunohistochemical phenotype of tumor cells was posi- tive for anti-CD3 and negative for anti-CD8 and anti-CD20. Therefore, morphological analysis diagnosed the mass as a multinodular bovine lymphosarcoma of T-cell origin with- out any sign of infection by a viral agent.

In the livestock feed industry, antibiotics are used to prevent disease, promote growth rate, and improve feed efficiency. However, antibiotic supplementation to animal feed results in increased bacterial resistance to antibiotics as well as antibiotic residues in animal products, which can negatively affect human health. Therefore, alternative sources of antibiotics are need- ed. Probiotics as an alternative to antibiotics in animal feed have been shown to increase feed efficiency and growth rate by improving microbial balance. Further, Bacillus sp. produces a wide spectrum of antibacte- rial peptides. The present study was conducted to investigate the effects of dietary supplementation with CS-32 on safety, growth rate, and feed efficiency. Antibacterial substance (5697.9 molecular weights) produced by CS-32 was isolated and purified from culture broth. Moreover, the results of minimal inhibi- tory concentration (MIC) test confirmed the excellent antibacterial effect of CS-32. In vivo, 0.1% and 1% CS-32 were fed to broiler chickens for 28 days. Feed efficiency was slightly higher in groups of chickens supplemented with 0.1% and 1% CS-32 than those of the control group. CS-32 had no significant effect on necropsy findings, hematology, or serum biochemistry, and there was no mortality. These results suggest that CS-32 among various biologically active substances may be safe and effective as a feed additive to improve growth rate and feed efficiency.

The purpose of this study was to explore the morphologi- cal characteristics of developing lentiform papilla (LP) in Korean native goats by scanning electron microscopy (SAM). Tongues were removed from fetuses on days 90, 120, neonates, and juveniles on days 30, 60, 90, 120, 150, and 180. In prenatal development, the primordia of LP in 90-day-old fetuses were round and spotted on the inner most part of the torus linguae of the tongue. Primordia of LP in 120-day-old fetuses also had a lens-like shape. In neonates, LP displayed similar features as the adult one. In postnatal juveniles on days 30 and 60, LP continually increased in size without much difference in structure compared to that of neonates. By postnatal day 90, detached pieces of keratinized super- ficial epithelia were observed. Microridges and microplicae were well developed on the epithelial surface of LP in 60- to 120-day-old goats. The lengths of LP were 476~514 μm in neonates, 687~962 μm in the weaning period of 60-day- old goats, and 1,068~1,567 μm in the maturing period of 180-day-old goats. These findings indicate that goat LP has different sizes and shapes from those of other species during development.

Mycoplasma (M.) hyopneumoniae is the causative agent of swine enzootic pneumonia, a disease that is prevalent in every country where pigs are raised. In this study, we aimed to develop a sensitive and specific PCR assay to detect M. hyopneumoniae in pigs. The suitability of this PCR assay for the detection of mycoplasmal infection was also tested using clinical lung samples from slaughtered pigs. We de- veloped a probe and M. hyopneumoniae-specific primer pairs, MhyoP-F and MhyoP-R, for the new PCR assay based on regions in the Mycoplasma protein P97 gene that are unique to M. hyopneumoniae. The developed PCR as- say was very specific and sensitive for the detection of M. hyopneumoniae. The assay was able to detect the equivalent of 10 pg of target template DNA, which indicates that the assay was very sensitive. In addition, the M. hyopneumoniae PCR assay detected only M. hyopneumoniae and no other Mycoplasma spp. or bacterial species of another genera. Further, the newly developed PCR assay effectively detected M. hyopneumoniae infection in pigs. We suggest that this PCR assay using M. hyopneumoniae-specific primer pairs, MhyoP-F and MhyoP-R, will be useful and effective for monitoring M. hyopneumoniae infection in pigs.

This study evaluated the efficacy and safety of medi- cal shampoo containing terbinafine hydrochloride and chlorhexidine gluconate in dogs with dermatophytos is complicated with bacterial infection. Although several stud- ies in dogs and cats with fungal dermatitis have found that oral administration of terbinafine is effective for controlling clinical signs, the topical form of terbinafine has rarely been studied in dogs and cats. Therefore, this study evaluated the efficacy of medical shampoo containing terbinafine hy- drochloride and chlorhexidine gluconate in dogs with der- matophytos is complicated with bacterial infection. Eight dogs infected with Microsporum spp. complicated with bacterial infection were enrolled in this study. These dogs were further blindly divided into Group 1 (no treatment, fourdogs) and group 2 (treated with medical shampoo with terbinafine/chlorhexidine, four dogs). Clinical improvement was evaluated using bacterial and fungal cultural evaluation combined with clinical evaluation. This study found that the medical shampoo has sufficient efficacy to treat varying degrees of dermatophytosis complicated with bacterial in- fection in dogs, although the speed of improvement differed according to the degree and type of infection. Our study also found that combined therapy using antifungal and antibac- terial agents can improve clinical signs more effectively and rapidly, suggesting that concurrent bacterial infection plays a significant role in the development of dermatitis.

The present study investigated the urinary tract toxicity of melamine alone or in combination with cyanuric acid in rats. Male rats were orally administered melamine alone (800 mg/kg) or melamine plus cyanuric acid (50 mg/kg each) for 3 consecutive days. Although melamine treatment did not show any significant difference in body weight, kid- ney or urinary bladder weight, serum blood urea nitrogen (BUN) or creatinine levels, it caused a decrease in urinary pH and mild histopathological alterations in the kidney and urinary bladder. In contrast, co-administration of melamine and cyanuric acid induced a decrease in body weight, an increase in kidneys and urinary bladder weights, and an elevation in serum BUN and creatinine levels, which were not observed in animals treated with melamine alone. His- topathological examination showed that the incidence and severity of histopathological lesions in the kidney and uri- nary bladder were much higher than those in the melamine group. Urinalysis revealed an increase in urine occult blood, leukocytes and protein and a decrease in urinary pH. These results indicate that concomitant administration of cyanuric acid synergistically potentiated the urinary tract toxicity induced by melamine in rats. In this study, we first demon- strated the synergistic toxic effects of melamine in combina- tion with cyanuric acid on urinary bladder and urinalysis in rats.

Patients referred to the Veterinary Medical Center at Chungbuk National University were analyzed. This study aimed to provide information to clinicians in Korea on the factors affecting fracture incidence in patients adapted to Korean companion animal culture. Eighty cases showing- bone fractures were investigated from January, 2005 to De- cember, 2011. Fractures were mainly observed in miniature dogs such as Yorkshire terrier (12%), Poodle (12%), and Maltese (9%). Almost 50% of all cases were less than 1 year old. Total bone fractures in summer and fall constituted 62%. Fracture incidence was higher in male dogs (54%) than female dogs (46%). Hindlimb fracture (37%) was the most common. Distribution of limb fractures was higher in the femur (19), followed by the tibia/fibula (15), radius/ulna (13), humerus (11), and mandible (8). Pelvic fracture was observed in 19 cases. Simple fracture (84%) was the most common fracture type, followed by comminuted fracture (16%). Distal portion was the most common fracture site in long bones (67%), followed by middle (26%) and proxi- mal bones (7%). Fractures were mainly caused by traffic accidents (43%), whereas 28.5% of fractures were due to falling down. Plate & screw (26%) was the most common method of fracture repair, followed by intramedullary pin (24%), wire (11%), external skeletal fixation (10%), screw (9%), amputation (7%), cross pin (6%), IM pin and wire (5%), and rush pin (1%). Among 80 patients, 79%of pa- tients showed a good prognosis after surgery, whereas 13% patients did not experience a good result. This study shows that miniature dogs are prone to falling and fractures, espe- cially in the distal part of long bones.

Effective treatment for community-acquired pneumonia (CAP) requires administration of appropriate empirical therapy based on etiologic, clinical, and radiological fea- tures. However, in Korea, CAP is poorly characterized, and data on viral CAP are particularly sparse. Therefore, im- proper use of antibiotics is common, and is detrimental the potential for development of bacterial. Thus, we investigated clinical and radiological findings for discrimination of viral CAP from bacterial CAP. Etiologic, clinical, and radiologi- cal data from 467 patients with CAP at Chungbuk National University Hospital from October 2010 to September 2011 were analyzed retrospectively. Viruses were identified in 23 cases (11.4%); the influenza virus A was the most common virus detected (N=18, 25.4%), followed by the respiratory syncytial virus A (N=14, 17.9%). Bacteria were identified in 48 cases (23.8%); Streptococcus-pneumonia was the most common (N=24, 25.5%), followed by Staphylococcus aureus (N=20, 21.3%). Depending on hospitalization time, the fol- lowing significant differences were observed between viral and bacterial CAP: on admission, (1) high fever (≥ 38.5°C), (2) purulent sputum, (3) white blood cell count, (4) C- reactive protein levels, (5) and bilateral lung involvement on chest X-ray were higher in bacterial CAP; and at discharge, (1) duration of high fever and (2) radiologic improvement within three days were higher in viral CAP. Regarding sea- sonal patterns, both viruses and bacteria have been identi- fied with relative frequency in the winter season. This study described the etiological, clinical, and radiological findings of viral and bacterial CAP. Conduct of additional large- scale, prospective investigations will be required in order to improve the appropriate treatment of CAP.

Cholangiocarcinoma is a relatively rare neoplasm in animals and humans. A four-year-old, neutered male ferret presented with depression, anorexia, cachexia diarrhea, and icterus. Necropsy findings included ascites multiple white nodules on the surface of the liver, stomach and duodenum, gross enlargement of the bile duct and right atrium, hemorrhage of the gastric and duodena mucosa, and icterus of the mesenteric fat. Infiltrative well differentiated neoplastic biliary epithelial cells forming ducts and acini with a prominent collagenous stroma were observed on microscopic examination of neoplastic lesions within the liver, mesentery, and the serosa of the stomach and duodenum. This is a report on a rare case of obstructive jaundice due to cholangiocarcinoma in a ferret.

A two-year-old, castrated male Jindo dog presented with a three-week history of non-pruritic alopecia and scales on dorsum. The dermatologic lesions were progressive and did not respond to antibiotics and treatment for ectoparasite. Silver-white scales were adhered to the hair shafts and a follicular cast was marked on a trichogram. Findings on histopathologic examination of the skin lesions were consistent with sebaceous adenitis. Treatment with systemic cyclosporine and topical shampoo treatment was recommended for long term management. This case report is the first to describe a sebaceous adenitis in our country and suggests combination treatment approaches to long term management of this disease.

The current study was conducted in order to investigate bone formation using matrigel and angiogenic factors with HA and poly ε-caprolactone (HA/PCL) in a rat calvarial defect model. Calvarial defect formation was surgically created in Sprague Dawley rats (n=36). Rats in the control group (CD group, n=6) did not receive a graft. The HA/ PCL scaffold was grafted with matrigel (M-HA/PCL group, n=6) or without matrigel (HA/PCL group, n=6); and 100 ng of vascular endothelial growth factor with HA/ PCL scaffold containing matrigel (VEGF100 group, n=6), 100 ng (PDGF100 group, n=6) and 300 ng (PDGF300 group, n=6) of PDGF with HA/PCL scaffold containing matrigel were grafted in calvarial defects, respectively. Four weeks after surgery, bone formation was evaluated with micro computed tomography (micro CT) scanning, and histologically. According to the results, bone mineral density was significantly increased in the VEGF100, PDGF100, and PDGF300 groups compared to the HA/PCL group, in which angiogenic factors were not applied. In histological evaluation, more new bone formation around scaffolds was observed in the PDGF100 and the PDGF300 groups, compared with the VEGF100 group. Thus, the results indicate that HA/PCL containing matrigel with VEGF and PDGF is an effective grafting material for enhancement of bone formation in critical-sized bone defects. Especially, due to its price and capacity for bone formation, PDGF may be more effective than VEGF.