• Biomolecules & Therapeutics
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• v.6 no.2
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• pp.171-181
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• 1998

DA-3585, a biosynthetic recombinant human erythropoietin has been developed as a treatment for anemia associated with chronic renal failure in Dong-A pharmaceutical Co. Ltd. This study was carried out to assess its acute and subacute toxicities in rabbits. DA-3585 was intravenously administered to rabbits at dose levels of 6250, 12500 or 25000 lU/kg for single dose toxicity study and at dose levels of 100, 500 or 2500 lU/kg/day for 4-week repeated dose toxicity study. In the acute toxicity study, dose up to 25000 lU/kg had no adverse effect on the behavior or body weight gain. Pathological examinations revealed no abnormal gross lesions related to DA-3585. In the subacute toxicity study, all animals survived until termination of treatment. DA-3585 had no influence on clinical signs, food and water intake or on body weight changes. Hematological examination showed increases in the number of RBC, hemoglobin contents and hematocrit values with a dose dependent manner in the animals treated with DA-3585. Histopathological examination revealed erythroid hyperplasia in the bone marrow and extramedullary hematopoiesis in the liver. The changes detected in the hematological and histopathological examination presumably represent exaggerated pharmacological effects of erythropoietin. The NOAEL (no-observed-adverse-effect-level) of DA-3585 was estimated to be 100 lU/kg/ day under this study condition.

• Parasites, Hosts and Diseases
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• v.49 no.3
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• pp.213-219
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• 2011

This experiment was conducted to assess the changing patterns and relative values of acute phase proteins and inflammatory cytokines in experimental caprine coccidiosis. Eighteen newborn kids were allocated to 3 equal groups. Two groups, A and B, were inoculated with a single dose of $1{\times}10^3$ and$1{\times}10^5$sporulated oocysts of Eimeria arloingi, respectively. The third group, C, received distilled water as the control. Blood samples were collected from the jugular vein of each kid in both groups before inoculation and at days 7, 14, 21, 28, 35, and 42 post-inoculation (PI), and the levels of haptoglobin (Hp), serum amyloid A (SAA), TNF-${\alpha}$, and IFN-${\gamma}$ were measured. For histopathological examinations, 2 kids were selected from each group, euthanized, and necropsied on day 42 PI. Mean Hp concentrations in groups A and B (0.34 and 0.68 g/L) at day 7 PI were 3.2 and 6.3 times higher than the levels before inoculation. The mean SAA concentrations in groups A and B (25.6 and 83.5 ${\mu}g$/ml) at day 7 PI were 4.2 and 13.7 times higher than the levels before inoculation. The magnitude and duration of the Hp and SAA responses correlated well with the inoculation doses and the severity of the clinical signs and diarrhea in kids. These results were consistent with the histopathological features, which showed advanced widespread lesions in group B. In both groups, significant correlations were observed for TNF-${\alpha}$ and IFN-${\gamma}$ with SAA and Hp, respectively. In conclusion, Hp and SAA can be useful non-specific diagnostic indicators in caprine coccidiosis.

• Development and Reproduction
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• v.23 no.2
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• pp.93-99
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• 2019

Nonylphenols (NPs) are widely used industrial materials, and are considered as potent endocrine disrupting chemical. Present study was undertaken to clarify the effect of subchronic low-dose NP exposure to F1 generation male mice. Mice were divided into 2 groups; (1) CON, control animals and (2) NP-50 ($50{\mu}g/L$), animals were treated with NP via drinking water. NP exposures were continuously conducted from parental pre-mating period until the postnatal day (PND) 55 of F1 offsprings. Mice were sacrificed on PND 55 and the tissue weights were measured. The initial body weights (at PND 21) and terminal body weights (PND 55) of the NP-50 animals were significantly lower than those of control animals (p<0.05). NP exposure induced a significant increase in the absolute weight of the testes (p<0.05). Conversely, the NP exposure caused significant decrease in the absolute weights of the epididymis (p<0.01), prostate (p<0.05) and seminal vesicle (p<0.05). Histopathological studies revealed that NP-treated animals exerted decreased seminiferous tubule diameters, reduced luminal area, and lower number of germ cells. Also some sloughing morphologies in the tubules were observed. In the caudal epididymis, fewer mature sperms and swollen epithelial cells were found in the NP-treated group. Our results confirmed that the subchronic low-dose NP exposure altered some male parameters and induced histopathological abnormalities in testis and epididymis of F1 mice. Since the NP dose used in this study is close to the average human daily NP exposure, our results could provide practically meaningful understanding of adverse effect of EDC in human.

• Microbiology and Biotechnology Letters
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• v.50 no.1
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• pp.51-62
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• 2022

Lactobacillus rhamnosus SKG34 (LrSKG34), a potential probiotic strain, was successfully isolated from Sumbawa Mare's milk. Our previous studies showed that the strain is resistant to gastrointestinal conditions, possesses antioxidant activity, and lowers blood cholesterol levels. Further clarification of the potential probiotic characteristics and safety assessment are necessary. This study aimed to evaluate the adhesion of LrSKG34 to Caco-2 cell monolayers and its effect on mucosal integrity in vitro. We also examined the LrSKG34 safety profile based on antimicrobial susceptibility testing, haemolytic activity determination, Caco-2 cell monolayer translocation evaluation, and in vivo investigation of the effect of LrSKG34 on the physiology, biochemical markers, and histopathological appearance of major organs in an animal model. LrSKG34 attached to Caco-2 cell monolayers and maintained mucosal integrity in vitro. The typical resistance of lactobacilli to ciprofloxacin, gentamicin, vancomycin, trimethoprim-sulfamethoxazole, and metronidazole was confirmed for LrSKG34. No haemolytic activity was observed on blood agar plates, and no LrSKG34 translocation was observed in Caco-2 cell monolayers. Administration of LrSKG34 to Sprague-Dawley rats did not adversely affect body weight. No abnormalities in hematological parameters, serum biochemistry levels, or histopathological structures of major organs were observed in LrSKG34-treated rats. Collectively, the results implicate LrSKG34 as a promising and potentially safe probiotic candidate for further development.

• Parasites, Hosts and Diseases
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• v.61 no.3
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• pp.251-262
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• 2023

Schistosomiasis causes significant morbidity and mortality worldwide. This study aimed to assess the effect of schistosomula lung antigen preparation (SLAP) and soluble egg antigen (SEA) on a murine schistosomiasis mansoni model. Ninety laboratory-bred male Swiss albino mice were divided into 6 groups. Two doses of the vaccine were given at 2-week intervals. All mice were subcutaneously infected with 80±10 Schistosoma mansoni cercariae 2 weeks after the last vaccination dose. They were sacrificed 7 weeks post-infection. Parasitological and histopathological studies were conducted to assess the effect of inoculated antigens (single or combined). The results showed that the combination of SLAP and SEA (combination group) led to a significant reduction in worm burden (65.56%), and liver and intestine egg count (59% and 60.59%, respectively). The oogram pattern revealed a reduction in immature and mature eggs (15±0.4 and 10±0.8, respectively) and an increased number of dead eggs in the combination group (P<0.001). In terms of histopathological changes, the combination group showed notably small compact fibrocellular egg granuloma and moderate fibrosis in the liver. A high percentage of destroyed ova was observed in the intestine of the combination group. This study demonstrates for the first time the prophylactic effect of combined SLAP and SEA vaccine. The vaccine induced a significant reduction in the parasitological and pathological impacts of schistosomiasis mansoni in hepatic and intestinal tissues, making it a promising vaccine candidate for controlling schistosomiasis.

• Archives of Plastic Surgery
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• v.35 no.3
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• pp.235-242
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• 2008

Purpose: Due to increasing interest in the treatment of spinal cord injuries, many histopathological studies have been conducted to prove that many neurotrophic factors including growth hormone are important for regeneration of the injured spinal cord. Growth hormone has to be given everyday, however, and this negatively affects compliance in clinical trials. Recently, the invention of sustained release growth hormone (SRGH) that can be given just once a week may both help the regeneration of injured spinal cord and, at the same time, be more compliant and convenient for clinical patients. Methods: In this study, thirty 7-week-old female Spraque-Dawley rats were subjected to a weight-driven impact spinal cord injury. They were divided into 3 groups and Group I and II were injected with SRGH once a week for 4 weeks; Group I were injected into the injured spinal cord area, while Group II were injected into the peritoneal cavity. Meanwhile, Group III were injected with normal saline solution. The functional outcome was evaluated using the Basso-Beattie-Bresnahan motor rating score and the inclined plane test was done 4 weeks after the first injection. Histopathological examination was performed at the same time and the amount of residual white matter was measured in all groups. Results: After 4 weeks, Groups I and II showed greater improvement than Group III(the control group) in the functional test. In the control group, invasion of atypical phagocytes, axonal degeneration, edema and cavity formation in the posterior site of spinal cord gray matter was observed in histopatholgical examination. The rate of residual white matter in Group III was less than in the other groups. Conclusion: Data showed significant functional and histopathological improvement in the groups treated with SRGH into the spinal and peritoneal cavity compared with the control group. SRGH is therefore beneficial because it helps with regeneration of the injured spinal cord and improves the compliance and convenience of patients.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6905-6911
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• 2013

Background: Breast cancer (BC) is the top cancer among women worldwide and the most frequent malignancy among Iranian women over the past few decades. The increasing trend and high mortality rate of BC in the developing world necessitates studies concentrating on its characteristics in countries in Asia. The current study focused on clinical and histopathological features of BC among Iranian females. Materials and Methods: This retrospective study involved 714 Iranian patients with histopathologically proven BC undergoing resection of primary tumours and axillary clearance. Demographic, clinical and histopathological data were obtained and studied between ten year age groups (${\leq}40$ years, 41-50 years, 51-60 years, 61-70 years, and ${\leq}71$ years) in four chronologic phases from 1994-2009. Results: Mean age of patients was $49.4{\pm}13.1$ years. Most of cases (33.2%) were in 41-50 group. Mean size of primary tumors was $3.94{\pm}2.47$ cm and 87.1% of cases had infiltrative ductal carcinoma. Modified radical mastectomy was the most common method of surgery carried out (48.8%). Some 57.1% of tumors were in pT2 and tumor size decreased significantly during the period (p<0.05). The most common BC stage was llla (27%). Lower BC stages (0 and 1) constituted 13.9% of the diagnosed tumors. Our series of patients aged ${\leq}40$ had larger tumors (mean $4.73{\pm}3.02$ cm) compared to older age groups (p=0.003). Lower stages (0 and I) were more frequent among the oldest patients while nearly 50% of patients aged ${\leq}40$ had tumor stage III. We also observed a significant decreasing trend in the mean LN count (p<0.05) and blood vessel invasion (p=0.023) from younger to older age groups. Conclusions: More aggressive disease for younger age groups, earlier peak incidence age and high rate of advanced BC at the time of diagnosis among Iranian women, were the main findings of this study.

• Journal of Periodontal and Implant Science
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• v.35 no.1
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• pp.235-250
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• 2005

The current interest in periodontal tissue regeneration has lead to research in bone graft, root surface treatments, guided-tissue regeneration, administration of growth factors, and the use of enamel matrix protein as possible means of regenerating lost periodontal tissue. Several studies have shown that a strong correlation between platelet-rich plasma and the stimulation of remodeling and remineralization of grafted bone exits, resulting in a possible increase of 15-30% in the density of bone trabeculae. The purpose of this study was to study the histopathological results and differences between the use of platelet-rich plasma and the use of enamel matrix $protein(Emdogain^?)$ about bone regeneration at the implant. Implant fixtures were inserted and graft materials placed into the left femur in the experimental group, while the only implant fixtures placed in the control group. In the first experimental group, platelet-rich plasma and xenograft were placed at the supracrestally placed implant site, and in the second experimental group, $Emdogain^{(R)}$ and xenograft placed at the supracrestally placed fixture site. The degree of bone regeneration adjacent to the implant fixture was observed and compared histopathologically at 2, 4, and 8 weeks after implant fixture insertion. The results of the experiment are as follows: 1. The rate of osseointegration to the fixture threads was found to be greater in the experimental group compared to in the control group. 2. The histopathological findings showed that the bone regeneration, the partial osseointegration existed at 4 weeks, and that osseointegration and bone density increaced in the experimental groups at 8 weeks. 3. The results showed that new bone formation and bone remodeling increased in the area near to the fixture in the first and second experimental groups at 8 weeks than at 4 weeks. The results showed that in the area distant from the fixture, new bone formation did not increase and bone remodeling decreased in the first experimental group at 4, 8 weeks, and that new bone formation increased in the second experimental group. 4. The histopathological findings showed that AZ deposition in the first experimental group was remarkable at 2, 8 weeks, and in the second experimental group at 2, 4, 8 weeks in the area distant from the fixture threads.

• Korean Journal of Bronchoesophagology
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• v.4 no.2
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• pp.211-218
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• 1998

There have been few large scale surveys of salivary gland tumors, because the salivary gland tumors comprised less than 3 percent of all neoplasms of the head and neck. Also there is a problem that the incidences of specific types of tumors have the variation according to the geographic regions. ]'nother Korean reports about salivary gland tumor, they only treated about 100 cases only. Objectives : The purpose of this study is to identify the frequency and clinical characteristics of salivary gland tumors and to compare with other Korean reports. Materials and Methods : We had performed to analyze 387 cases of salivary gland tumors from 1983 to June 1997, were reviewed in histopathological and clinical aspects. The diagnoses of individual tumors were based on the World Health Organization classification. Tumors were analyzed according to the histologic type site, age and sex. Results : The majority (79.1%) of cases occurred in the major salivary glands and 20.9% in the minor. The parotid gland was the most frequent site with 52.4％ and submandibular glands with 26.3%. Benign tumors were 79.3% of the tumors and malignant tmon were 20.7%. The most frequent tumor was pleomorphic adenoma occupied 63.8% of the total and frequency percent of histologic type of 98 malignant tumors showed 35.7% of mucoepidermoid carcinomas, 24.5% of adenoid cystic carcinomas. Overall gender with female predominance with 1 : 1.4 of male to female ratio. The average age of patients was 42.8 years. The most frequent chief complaint was a palpable mass. The duration of the symptom was shorter in the malignant salivary gland tumors (26.7 months) than in the benign salivary gland tumors (38.2 months). Conclusion : Comparing to the previous Korean reports, the present study confirms that the incidence of salivary gland tumor was lower in the parotid gland, and was higher in the submandibular and minor salivary glands.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.34 no.3
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• pp.173-178
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• 2001

This study was performed to know the hypocholesterolemic effect of depolymerized alginate obtained by hydrolysis of alginate through a heating process at $121^{\circ}C$. The changes of total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides and phospholipid levels in serum, as well as the atherogenic index were elucidated in rats for 35 days. In order to evaluate single-dose toxicity of HAG-50 in rats via oral routes, induction any mortalities and abnormal signs in clinical finding, body weight, gross findings and histopathological finding, and estimation of $LD_{50}$ were elucidated. Total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides and phospholipid levels in the serum significantly decreased and resulted in the decrease of atherogenic index in rats fed diets containing $5\%\;and\;10\%$ HAG-50 (p<0.01). HAG-50 did not induce any mortalities and abnormal signs in clinical findings, body weights, gross findings and histopathological findings in single-dose toxicity test via oral routes of rats, after which it was impossible to estimate $LD_{50}$ values.