SARS‑CoV‑2 Omicron variant causes brain infection with lymphoid depletion in a mouse COVID‑19 model / 한국실험동물학회지

Background@#The Omicron variant has become the most prevalent SARS-CoV-2 variant. Omicron is known to induce milder lesions compared to the original Wuhan strain. Fatal infection of the Wuhan strain into the brain has been well documented in COVID-19 mouse models and human COVID-19 cases, but apparent infections into the brain by Omicron have not been reported in human adult cases or animal models. In this study, we investigated whether Omicron could spread to the brain using K18-hACE2 mice susceptible to SARS-CoV-2 infection. @*Results@#K18-hACE2 mice were intranasally infected with 1 × 105 PFU of the original Wuhan strain and the Omicron variant of SARS-CoV-2. A follow-up was conducted 7 days post infection. All Wuhan-infected mice showed > 20% body weight loss, defined as the lethal condition, whereas two out of five Omicron-infected mice (40%) lost > 20% body weight. Histopathological analysis based on H&E staining revealed inflammatory responses in the brains of these two Omicron-infected mice. Immunostaining analysis of viral nucleocapsid protein revealed severe infection of neuron cells in the brains of these two Omicron-infected mice. Lymphoid depletion and apoptosis were observed in the spleen of Omicron-infected mice with brain infection. @*Conclusion@#Lethal conditions, such as severe body weight loss and encephalopathy, can occur in Omicron-infected K18-hACE2 mice. Our study reports, for the first time, that Omicron can induce brain infection with lymphoid depletion in the mouse COVID-19 model.

Laboratory information management system for COVID-19 non-clinical efficacy trial data / 한국실험동물학회지

Background@#As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. @*Results@#In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. @*Conclusions@#This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.

C1qa deficiency in mice increases susceptibility to mouse hepatitis virus A59 infection

Background@#Mouse hepatitis virus (MHV) A59 is a highly infectious pathogen and starts in the respiratory tract and progresses to systemic infection in laboratory mice. The complement system is an important part of the host immune response to viral infection. It is not clear the role of the classical complement pathway in MHV infection. @*Objectives@#The purpose of this study was to determine the importance of the classical pathway in coronavirus pathogenesis by comparing C1qa KO mice and wild-type mice. @*Methods@#We generated a C1qa KO mouse using CRISPR/Cas9 technology and compared the susceptibility to MHV A59 infection between C1qa KO and wild-type mice. Histopathological and immunohistochemical changes, viral loads, and chemokine expressions in both mice were measured. @*Results@#MHV A59-infected C1qa KO mice showed severe histopathological changes, such as hepatocellular necrosis and interstitial pneumonia, compared to MHV A59-infected wildtype mice. Virus copy numbers in the olfactory bulb, liver, and lungs of C1qa KO mice were significantly higher than those of wild-type mice. The increase in viral copy numbers in C1qa KO mice was consistent with the histopathologic changes in organs. These results indicate that C1qa deficiency enhances susceptibility to MHV A59 systemic infection in mice. In addition, this enhanced susceptibility effect is associated with dramatic elevations in spleen IFN-γ, MIP-1 α, and MCP-1 in C1qa KO mice. @*Conclusions@#These data suggest that C1qa deficiency enhances susceptibility to MHV A59 systemic infection, and activation of the classical complement pathway may be important for protecting the host against MHV A59 infection.

SARS-CoV-2 Omicron Mutation Is Faster than the Chase: Multiple Mutations on Spike/ACE2 Interaction Residues

Recently, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (B.1.1.529) Omicron variant originated from South Africa in the middle of November 2021. SARS-CoV-2 is also called coronavirus disease 2019 (COVID-19) since SARS-CoV-2 is the causative agent of COVID-19. Several studies already suggested that the SARS-CoV-2 Omicron variant would be the fastest transmissible variant compared to the previous 10 SARS-CoV-2 variants of concern, interest, and alert. Few clinical studies reported the high transmissibility of the Omicron variant but there is insufficient time to perform actual experiments to prove it, since the spread is so fast. We analyzed the SARS-CoV-2 Omicron variant, which revealed a very high rate of mutation at amino acid residues that interact with angiostatin-converting enzyme 2. The mutation rate of COVID-19 is faster than what we prepared vaccine program, antibody therapy, lockdown, and quarantine against COVID-19 so far. Thus, it is necessary to find better strategies to overcome the current crisis of COVID-19 pandemic.

C1qa deficiency in mice increases susceptibility to mouse hepatitis virus A59 infection

Background@#Mouse hepatitis virus (MHV) A59 is a highly infectious pathogen and starts in the respiratory tract and progresses to systemic infection in laboratory mice. The complement system is an important part of the host immune response to viral infection. It is not clear the role of the classical complement pathway in MHV infection. @*Objectives@#The purpose of this study was to determine the importance of the classical pathway in coronavirus pathogenesis by comparing C1qa KO mice and wild-type mice. @*Methods@#We generated a C1qa KO mouse using CRISPR/Cas9 technology and compared the susceptibility to MHV A59 infection between C1qa KO and wild-type mice. Histopathological and immunohistochemical changes, viral loads, and chemokine expressions in both mice were measured. @*Results@#MHV A59-infected C1qa KO mice showed severe histopathological changes, such as hepatocellular necrosis and interstitial pneumonia, compared to MHV A59-infected wildtype mice. Virus copy numbers in the olfactory bulb, liver, and lungs of C1qa KO mice were significantly higher than those of wild-type mice. The increase in viral copy numbers in C1qa KO mice was consistent with the histopathologic changes in organs. These results indicate that C1qa deficiency enhances susceptibility to MHV A59 systemic infection in mice. In addition, this enhanced susceptibility effect is associated with dramatic elevations in spleen IFN-γ, MIP-1 α, and MCP-1 in C1qa KO mice. @*Conclusions@#These data suggest that C1qa deficiency enhances susceptibility to MHV A59 systemic infection, and activation of the classical complement pathway may be important for protecting the host against MHV A59 infection.

in vivo multiplex gene targeting with Streptococcus pyogens and Campylobacter jejuni Cas9 for pancreatic cancer modeling in wildtype animal

Pancreatic ductal adenocarcinoma is a lethal cancer type that is associated with multiple gene mutations in somatic cells. Genetically engineered mouse is hardly applicable for developing a pancreatic cancer model, and the xenograft model poses a limitation in the reflection of early stage pancreatic cancer. Thus, in vivo somatic cell gene engineering with clustered regularly interspaced short palindromic repeats is drawing increasing attention for generating an animal model of pancreatic cancer. In this study, we selectedKras, Trp53, Ink4a, Smad4, and Brca2 as target genes, and applied Campylobacter jejuni Cas9 (CjCas9) andStreptococcus pyogens Cas9 (SpCas9) for developing pancreatic cancer using adeno associated virus (AAV) transduction. After confirming multifocal and diffuse transduction of AAV2, we generated SpCas9 overexpression mice, which exhibited high double-strand DNA breakage (DSB) in target genes and pancreatic intraepithelial neoplasia (PanIN) lesions with two AAV transductions; however, wild-type (WT) mice with three AAV transductions did not develop PanIN. Furthermore, small-sized Cjcas9 was applied to WT mice with two AAV system, which, in addition, developed high extensive DSB and PanIN lesions. Histological changes and expression of cancer markers such as Ki67, cytokeratin, Mucin5a, alpha smooth muscle actin in duct and islet cells were observed. In addition, the study revealed several findings such as 1) multiple DSB potential of AAV-CjCas9, 2) peri-ductal lymphocyte infiltration, 3) multi-focal cancer marker expression, and 4) requirement of > 12 months for initiation of PanIN in AAV mediated targeting. In this study, we present a useful tool for in vivo cancer modeling that would be applicable for other disease models as well.

Comparison of the virulence of Streptococcus pneumoniae in ICR mouse stocks of three different origins / 한국실험동물학회지

Streptococcus pneumoniae causes many people to suffer from pneumonia, septicemia, and other diseases worldwide. To identify the difference in susceptibility of and treatment efficacy against S. pneumoniae in three ICR mouse stocks (Korl: ICR, A:ICR, and B:ICR) with different origins, mice were infected with 2 × 106, 2×107, and 2×108 CFU of S. pneumoniae D39 intratracheally. The survival of mice was observed until three weeks after the infection. The three stocks of mice showed no significant survival rate difference at 2 × 106 and 2 × 107 CFU. However, the lung and spleen weight in the A:ICR stock was significantly different from that in the other two stocks, whereas the liver weight in B:ICR stock was significantly lower than that in the other two stocks. Interestingly, no significant CFU difference in the organs was observed between the ICR stocks. The level of interferon gamma inducible protein 10 in Korl:ICR was significantly lower than that in the other two stocks. The level of granulocyte colony stimulating factor in B:ICR was significantly lower than in the other two stocks. However, tumor-necrosis factor-alpha and interleukin-6 levels showed no significant difference between the ICR stocks. In the vancomycin efficacy test after the S. pneumoniae infection, both the single-dose and double-dose vancomycin-treated groups showed a significantly better survival rate than the control group. There was no significant survival difference between the three stocks. These data showed that Korl:ICR, A:ICR, and B:ICR have no susceptibility difference to the S. pneumoniae D39 serotype 2.

Additive Effects of Rebamipide Plus Proton Pump Inhibitors on the Expression of Tight Junction Proteins in a Rat Model of Gastro-Esophageal Reflux Disease

BACKGROUND/AIMS: The aim of this study was to investigate the effects of rebamipide on tight junction proteins in the esophageal mucosa in a rat model of gastroesophageal reflux disease (GERD). METHODS: GERD was created in rats by tying the proximal stomach. The rats were divided into a control group, a proton pump inhibitor (PPI) group, and a PPI plus rebamipide (PPI+R) group. Pantoprazole (5 mg/kg) was administered intraperitoneally to the PPI and PPI+R groups. An additional dose of rebamipide (100 mg/kg) was administered orally to the PPI+R group. Mucosal erosions, epithelial thickness, and leukocyte infiltration into the esophageal mucosa were measured in isolated esophagi 14 days after the procedure. A Western blot analysis was conducted to measure the expression of claudin-1, -3, and -4. RESULTS: The mean surface area of mucosal erosions, epithelial thickness, and leukocyte infiltration were lower in the PPI group and the PPI+R group than in the control group. Western blot analysis revealed that the expression of claudin-3 and -4 was significantly higher in the PPI+R group than in the control group. CONCLUSIONS: Rebamipide may exert an additive effect in combination with PPI to modify the tight junction proteins of the esophageal mucosa in a rat model of GERD. This treatment might be associated with the relief of GERD symptoms.

Establishment of a mouse model of 70% lethal dose by total-body irradiation / 한국실험동물학회지

Whereas increasing concerns about radiation exposure to nuclear disasters or side effects of anticancer radiotherapy, relatively little research for radiation damages or remedy has been done. The purpose of this study was to establish level of LD70/30 (a lethal dose for 70% of mice within 30 days) by total-body γ irradiation (TBI) in a mouse model. For this purpose, at first, 8-week-old male ICR and C57BL/6N mice from A and B companies were received high dose (10, 11, 12 Gy) TBI. After irradiation, the body weight and survival rate were monitored for 30 days consecutively. In next experiment, 5-week-old male ICR and C57BL/6N mice from B company were received same dose irradiation. Results showed that survival rate and body weight change rate in inbred C57BL/6N mice were similar between A and B company. In ICR mice, however, survival rate and body weight change rate were completely different among the companies. Significant difference of survival rate both ICR and C57BL6N mice was not observed in between 5-week-old and 8-week-old groups receiving 10 or 12 Gy TBI. Our results indicate that the strain and age of mice, and even purchasing company (especially outbred), should be matched over experimental groups in TBI experiment. Based on our results, 8-week-old male ICR mice from B company subjected to 12 Gy of TBI showed LD70/30 and suitable as a mouse model for further development of new drug using the ideal total-body irradiation model.

Helicobacter apodemus sp. nov., a new Helicobacter species identified from the gastrointestinal tract of striped field mice in Korea

A novel Helicobacter species was identified from the gastrointestinal tract of the Korean striped field mouse (Apodemus agrarius). Biochemical testing, ultrastructure characterization, and 16S rRNA gene sequence analysis suggested that this bacterium represents a distinct taxon. The bacterium was positive for urease activity, susceptible to cephalothin and nalidixic acid, and weakly positive for oxidase and catalase activity. Electron microscopy revealed that the bacterium has spirally curved rod morphology with singular bipolar nonsheathed flagella. Genotypically, the isolated bacterial strains (YMRC 000215, YMRC 000216, and YMRC 000419) were most closely related to a reference strain of Helicobacter mesocricetorum (97.25%, 97.32%, and 97.03% 16S rRNA sequence similarities, respectively). The 16S rRNA sequences of these strains were deposited into GenBank under accession numbers AF284754, AY009129, and AY009130, respectively. We propose the name Helicobacter apodemus for this novel species.

Tumor necrosis factor-alpha deficiency impairs host defense against Streptococcus pneumoniae / 한국실험동물학회지

Streptococcus pneumoniae is a major human pathogen that is involved in community-acquired pneumonia. Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine that activates immune responses against infection, invasion, injury, or inflammation. To study the role of TNF-alpha during S. pneumoniae infection, a murine pneumococcal pneumonia model was used. We intranasally infected C57BL/6J wild-type (WT) and TNF-alpha knockout (KO) mice with S. pneumoniae D39 serotype 2. In TNF-alpha KO mice, continuous and distinct loss of body weight, and low survival rates were observed. Bacterial counts in the lungs and blood of TNF-alpha KO mice were significantly higher than those in WT mice. Histopathological lesions in the spleen of TNF-alpha KO mice were more severe than those in WT mice. In TNF-alpha KO mice, severe depletion of white pulp was observed and the number of apoptotic cells was significantly increased. Interferon-gamma (IFN-gamma), IL-12p70 and IL-10 levels in serum were significantly increased in TNF-alpha KO mice. TNF-alpha is clearly involved in the regulation of S. pneumoniae infections. Early death and low survival rates of TNF-alpha KO mice were likely caused by a combination of impaired bacterial clearance and damage to the spleen. Our findings suggest that TNF-alpha plays a critical role in protecting the host from systemic S. pneumoniae infection.

Evaluation of General Toxicity and Genotoxicity of the Silkworm Extract Powder

The silkworm extract powder contain 1-deoxynojirimycin (DNJ), a potent alpha-glycosidase inhibitor, has therapeutic potency against diabetes mellitus. Therefore, natural products containing DNJ from mulberry leaves and silkworm are consumed as health functional food. The present study was performed to evaluate the safety of the silkworm extract powder, a health food which containing the DNJ. The repeated toxicity studies and gentic toxicity studies of the silkworm extract powder were performed to obtain the data for new functional food approval in MFDS. The safety was evaluated by a single-dose oral toxicity study and a 90 day repeated-dose oral toxicity study in Sprague-Dawley rats. The silkworm extract powder was also evaluated for its mutagenic potential in a battery of genetic toxicity test: in vitro bacterial reverse mutation assay, in vitro chromosomal aberration test, and in vivo mouse bone marrow micronucleus assay. The results of the genetic toxicology assays were negative in all of the assays. The approximate lethal dose in single oral dose toxicity study was considered to be higher than 5000 mg/kg in rats. In the 90 day study, the dose levels were wet at 0, 500, 1000, 2000 mg/kg/day, and 10 animals/sex/dose were treated with oral gavage. The parameters that were monitored were clinical signs, body weights, food and water consumptions, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, organ weights, and histopathological examination. No adverse effects were observed after the 90 day administration of the silkworm extract powder. The No-Observed-Adverse-Effect-Level (NOAEL) of silkworm extract powder in the 90 day study was 2000 mg/kg/day in both sexes, and no target organ was identified.

Preventive Effects of Zoledronic Acid on Bone Metastasis in Mice Injected with Human Breast Cancer Cells

Bisphosphonates are used routinely to reduce bone-related events in breast cancer patients with bone metastasis. We evaluated the effects of zoledronic acid, a third generation, nitrogen-containing bisphosphonate, to prevent bone metastasis in breast cancer. Zoledronic acid or vehicle alone was administered to nude mice either simultaneously or after intracardiac injection of human breast cancer MDA-MB-231 cells. Nude mice treated with zoledronic acid at early time points showed a lower incidence of bone metastases than did vehicle-treated nude mice, but these differences were not statistically significant. Only 37.5% of mice treated with zoledronic acid at the time of tumor cell inoculation developed bone metastases compared to over 51.8% of mice receiving vehicle alone (P = 0.304). Cell count of apoptosis confirmed by immunohistochemical staining in metastatic bone tissue significantly increased in the zoledronic acid-treated groups compared to non-treated group (1,018.3 vs 282.0; P = 0.046). However, metastatic tumor cells, which invade soft tissue around the bone, did not show extensive apoptosis; there were no differences between the zoledronic acid-treated and control groups. These results suggest that zoledronic acid increases apoptosis of metastatic breast tumor cells in the bone and could therefore reduce metastatic tumor burden. These results support the use of zoledronic acid to reduce the incidence of bone metastasis in breast cancer.

Difference in Resistance to Streptococcus pneumoniae Infection in Mice / 한국실험동물학회지

Streptococcus pneumoniae is a major pathogen that causes various diseases, including pneumonia and sepsis, as millions of people suffer from S. pneumoniae infection worldwide. To better understand the immune and inflammatory responses to S. pneumoniae, we produced murine models. To investigate the differences between intranasal and intratracheal infection, BALB/c mice were infected with S. pneumoniae D39 intranasally or intratracheally. Mice showed no significant differences in survival rates, body weight changes, and bacterial loads. To investigate resistance and susceptibility among mouse strains, BALB/c, C57BL/6J, tumor necrosis factor-alpha (TNF-alpha) knockout, and interleukin-10 (IL-10) knockout mice were infected with S. pneumoniae D39 via intranasal or intravenous routes. In this study, BALB/c and C57BL/6J mice were resistant, IL-10 knockout mice were intermediate, and TNF-alpha knokout mice were susceptible to S. pneumoniae infection. These data show that intranasal and intratracheal infection induced similar results after S. pneumoniae infection, and the genetic background of mice must be considered when studying S. pneumoniae infection in vivo.

A Study of the Effect of a Mixture of Hyaluronic Acid and Sodium Carboxymethyl Cellulose (Guardix-sol(R)) on the Prevention of Pericardial Adhesion / 대한흉부외과학회지

BACKGROUND: This study was designed to evaluate the efficacy of a mixture of hyaluronic acid and sodium carboxymethyl cellulose (Guardix-sol(R)) on experimental pericardial adhesion. MATERIAL AND METHOD: Thirty rats were divided into 2 groups of 15 rats each and pericardial mesothelial injury was induced during surgery by abrasion. In the control group, blood and normal saline were administered into pericardium; in the test group, blood and HA-CMC solution were administered. Pericardial adhesions were evaluated at 2 weeks (n=5), 4 weeks (n=5), and 6 weeks (n=5) after surgery. The severity of adhesions was graded by macroscopic examination, and the adhesion tissue thickness was analyzed microscopically with Masson trichrome stain and an image processing program. RESULT: The test group had significantly lower macroscopic adhesion scores (2.9+/-0.6 : 3.9+/-0.4, p<0.000) compared with the control group. For microscopic adhesion tissue thickness, the test group had lower scores compared with the control group, but this difference was not statistically significant (91.73+/-49.91 : 117.67+/-46.4, p=0.106). CONCLUSION: We conclude that an HA-CMC solution (Guardix-sol(R)) reduces the formation of pericardial adhesions in this animal model.

A Novel Model for Human Atopic Dermatitis: Application of Repeated DNCB Patch in BALB/c Mice, in Comparison with NC/Nga Mice / 한국실험동물학회지

The various murine models have contributed to the study of human atopic dermatitis (AD). However limitations of the models involve low reproducibility and long time to develop AD. In an attempt to overcome these limitations and establish an atopic dermatitis murine model, we repeated the application of 2, 4-dinitrochlorobenzene (DNCB) patch in NC/Nga and BALB/c mice, which has advantages in reproduction and cost. For the sensitization, a 1 cm2 gauze-attached patch, where 1% or 0.2% DNCB was periodically attached on the back of NC/Nga and BALB/c mice. To estimate how homologous our model was with human atopic dermatitis, clinical, histological and immunological alterations were evaluated. Both strains showed severe atopic dermatitis, increase in subiliac lymph node weight, mast cells, epidermal hyperplasia and serum IgE levels. Though both exhibited a high IL-4/IFN-gamma and IL-4/TNF-beta ratio in the expression of mRNA, the shifting of DNCB-treated BALB/c mice was increased to more than double that of NC/Nga mice. These results suggest that our DNCB patched model using BALB/c mice were more suitable than NC/Nga mice in demonstrating the immune response. We anticipate that our novel model may be successfully used for pathogenesis of atopic dermatitis and assessment of therapeutic approaches.

Angioimmunoblastic T Cell Lymphomas: Frequent Cutaneous Skin Lesions and Absence of Human Herpes Viruses

BACKGROUND: Angioimmunoblastic T-cell lymphoma (AITL) is a complex lymphoproliferative disorder and often mimics a viral infection with frequent skin involvement. Epstein-Barr virus (EBV) and human herpes virus (HHV)-6 are reported to be associated with AITL, but there are conflicting results. OBJECTIVE: We evaluated the association of EBV and HHV-6 with AITL. METHODS: We reviewed the clinical, histological and immunophenotypical features of 19 cases of AITL. Among them, 11 lymph node biopsies of AITL were examined for HHV-6, -7, and -8 by polymerase chain reaction (PCR) using virus-specific primers. In situ hybridization of EBV early region RNA (EBER) was performed and T cell receptor (TCR) gene rearrangement was also investigated in some cases. RESULTS: Among these 19 cases, maculopapular, plaque or nodular skin lesions accompanied AITL in 12 cases. Clonal TCR gene rearrangement was seen in 8/9 cases tested. EBER in situ hybridization was positive in 8 cases (57.1%). Among 7 cases with skin biopsies, five cases were consistent with cutaneous involvement of AITL, 1 case was a drug eruption, and the other case was Kaposi's sarcoma. Except a HHV-8 (+) case who also had Kaposi's sarcoma, all of these cases were negative for HHV-6, -7 and -8. CONCLUSION: Skin manifestation seems to be a cardinal component of AITL, be it in the context of presentation, progression or recurrent disease. Recognition of clinicopathological features of skin lesions in AITL as diagnostic clues should be stressed among dermatologists. The lack of HHV-6, -7 and -8 in lymph node biopsy of AITL argues against a pathogenic role for HHVs in AITL.

Retrospective study of canine cutaneous tumors in Korea

Over the 42 month period from January 2003 to June2006, a total of 2,952 canine biopsy specimens werereceived from the Veterinary Medical Teaching Hospitalof Seoul National University and from veterinary practitionersacross the nation. Out of these, 748 (25.34%) cases werediagnosed as canine cutaneous tumors in the Departmentof Veterinary Pathology, College of Veterinary Medicine,Seoul National University, Korea. Thirty-eight differenttypes of cutaneous tumors were identified and categorizedinto epithelial and melanocytic tumors (56.95%), mesenchymaltumors (38.90%), and hematopoietic tumors (4.14%)located in the skin. Among these, 69.25% were benign and30.74% were malignant. The top ten most frequentlydiagnosed cutaneous tumors were epidermal and follicularcysts (12.70%), lipoma (11.36%), mast cell tumors (8.82%),cutaneous histiocytoma (7.49%), basal cell tumors (6.82%),sebaceous gland adenoma (6.68%), sebaceous glandhyperplasia (5.08%), hepatoid gland adenoma (3.61%),apocrine adenocarcinoma (3.07%), and fibroma (2.81%),in order of prevalence. They comprised 68.45% of allcutaneous tumors. These top ten cutaneous tumors weredistributed on the trunk (30.08%), head and neck(20.9%), extremities (19.14%), anal and perianal area(8.59%), and tail (3.91%). The age of the dogs with the tenmost frequent tumors had a mean age of 8.3 years, with arange of 2 months to 19 years. When all types of tumorswere considered together in the entire population, therewas no difference in incidence according to sex.

Expression of Human beta-defensin mRNA in Epidermal Proliferative Diseases / 대한피부과학회지

BACKGROUND: Defensins are cationic antimicrobial peptides with a wide range of antimicrobial activity against gram positive and gram negative bacteria, yeasts, fungi, and viruses. They are also believed to promote a rapid cellular immune response to infection via chemotactic effect on monocyte. In addition to their antimicrobial actions, defensins may accelerate wound healing by virtue of their mitogenic effect on epithelial cells and fibroblasts. OBJECTIVES: We performed this study to investigate the characterization of human beta-defensin (hBD)-1, -2 and -3 mRNA expression in epidermal proliferative diseases. METHODS: The level of expression of hBD-1, -2 and -3 mRNA was analyzed by reverse transcription-polymerase chain reaction(RT-PCR) assay and densitometry in epidermal proliferative diseases. RESULTS: hBD-1, -3 mRNAs were expressed in normal human epidermis and more readily detectable in epidermal proliferative diseases such as psoriasis vulgaris, prurigo nodularis, proliferative lichen planus, lichen simplex chronicus. But the expression of hBD-1 mRNA in psoriasis vulgaris mRNA was not significantly increased. hBD-2 mRNA was not detected in normal human epidermis and epidermal proliferative diseases with the exception of psoriasis vulgaris. CONCLUSION: These expressions of human beta defensin mRNAs in the epidermal proliferative diseases suggest that human beta defensin may have a close relationship with skin inflammations.

Urodynamic Effect of Oxybutynin Chloride on Bladder Dysfunction in Rats with Focal Cerebral Ischemia

PURPOSE: The purpose of this study was to evaluate the urodynamic effect of oxybutynin chloride on bladder dysfunction in rats with focal cerebral ischemia. MATERIALS AND METHODS: The cerebral infarction of 8 to 9 week-old male Sprague-Dawley rats was induced by occlusion of the left middle cerebral artery. The control groups received sham operation. At 1, 2 and 4 weeks after operation, cystometrogram (CMG) was performed before and after intravesical instillation of 0.5 ml of oxybutynin chloride (0.005 and 0.05 mg/ml) (n=7). RESULTS: The body weight of cerebral-infarcted (CI) rats was smaller than that of sham-operated rats. Compared to sham-operated rats, CI rats showed a shorter voiding interval, smaller micturition pressure, smaller voiding volume and more residual urine. in CMG. After intravesical instillation of oxybutynin, CMG showed dose-dependent increase of voiding interval and functional bladder volume and decrease of peak micturition pressure. The effects of oxybutynin on CI rats were more prominant than that of sham-operated rats. CONCLUSIONS: CI rats showed urinary frequency and decrease of micturition pressure in CMG. The result of this study will be useful for explanation of the detrusor hyperactivity with impaired contractility (DHIC) in patients with cerebral infarction. These results suggest that treatment with intravesical oxybutynin will be an effective alternative treatment of detrusor hyperactivities with cerebral infarction.