Effect of Environmental Factors on Depressive-like Behavior and Memory Function in Adolescent Rats

PURPOSE: The aim of this study was to identify the effects of environmental factors on depressive-like behavior and memory function during adolescence. We performed behavior tests in adolescent rats exposed to environmental enrichment, handling, and social deprivation for eight weeks. METHODS: Wistar rats were randomly assigned to control, environmental enrichment, handling, and social deprivation groups at the age of four weeks. RESULTS: In the forced swim test, the immobility time in the environmental enrichment group was decreased than that in the control group (p=.038), while the immobility time in the social deprivation group was increased than that in the control group (p=.035), the environmental enrichment group (p<.001), and the handling group (p=.001). In the Morris water maze test, the social deprivation group had an increased latency time than the control group (p=.013) and the environmental enrichment group (p=.001). In the passive avoidance test, the environmental enrichment group had an increased latency time than the control group (p=.005). However, the social deprivation group had reduced latency time than the socially housed groups (control: p=.030; environmental enrichment: p<.001; handling: p<.001). CONCLUSION: These findings suggest that environmental factors play an important role in emotion and memory function during adolescence.

Effect of Environmental Enrichment on Cognitive Impairment-induced by Ethanol Exposure in Adolescent Rat

PURPOSE: Adolescents who experienced the alcohol consumption have gradually increased. Adolescence is a critical period of the neural plasticity in the brain. Neural plasticity is mediated by neurotrophins and has an impact on cognitive function. Environmental enrichment ameliorates the cognitive function and increases neurotrophins. Thus, we investigated the neuroprotective effect of environmental enrichment on ethanol induced cognitive impairment in adolescent rats. METHODS: The ethanol groups and the controls groups were injected with ethanol (0.5g/kg) and phosphate buffered saline, respectively, through intraperitoneal from 28th day of birth for 11 days. The environmental enrichment groups were provided larger cages containing toys than the standard cage . Passive avoidance test and Y-maze test were performed to evaluate the spatial memory. RESULTS: Environmental enrichment+ethanol group showed higher alterations than the standard environment+ethanol group in Y-maze test (p<.05). In hippocampus, The environmental enrichment+ethanol group showed significantly higher level of the number of c-fos positive celsl and density of tropomyosin receptors kinase B receptor than the standard environment+ethanol group (p<.05). CONCLUSION: So, we suggested that the environmental enrichment played a role as a prophylaxis for prevention of memory impairment induced by ethanol exposure in adolescence.

Effect of Saccharin Intake in Restraint-induced Stress Response Reduction in Rats

PURPOSE: Stress activates the sympathetic nervous system and hypothalamic-pituitary-adrenal (HPA) axis and induces the release of glucocorticoids. Saccharin is 300 times sweeter than sucrose, but does not increase blood insulin levels. Thus, this study was designed to evaluate the effect of saccharin intake in restraint-induced stress response reduction in rats. METHODS: Adult male Sprague-Dawley (SD) rats had stress induced by restraint for 2 hours/day for 1 week. Saccharin was provided in sufficient amounts to allow them to intake it voluntarily at 0.1% diluted in water. The Y-maze test and forced swim test (FST) were performed to evaluate cognitive function and the depressive behavior of the rats. The protein expression of the glucocorticoid receptor (GR) in hippocampal cornu ammonis (CA) 1 was investigated by using immunohistochemistry. RESULTS: It was found that, the percentage of alternation in the Y-maze test was significantly (p<.01) higher in the Stress + saccharin group than in the Stress group. Immobility time in the FST was significantly (p<.01) lower in the Stress + saccharin group than in the Stress group. Also, the positive cells of GR in hippocampus CA1 were significantly (p<.05) lower in the Stress + saccharin group than in the Stress group. CONCLUSION: This study showed that there was an effect of saccharin intake in restraint-induced stress response reduction in rats.

Acute exposure to silica nanoparticles aggravate airway inflammation: different effects according to surface characteristics

Silica nanoparticles (SNPs) are widely used in many scientific and industrial fields despite the lack of proper evaluation of their potential toxicity. This study examined the effects of acute exposure to SNPs, either alone or in conjunction with ovalbumin (OVA), by studying the respiratory systems in exposed mouse models. Three types of SNPs were used: spherical SNPs (S-SNPs), mesoporous SNPs (M-SNPs), and PEGylated SNPs (P-SNPs). In the acute SNP exposure model performed, 6-week-old BALB/c female mice were intranasally inoculated with SNPs for 3 consecutive days. In the OVA/SNPs asthma model, the mice were sensitized two times via the peritoneal route with OVA. Additionally, the mice endured OVA with or without SNP challenges intranasally. Acute SNP exposure induced significant airway inflammation and airway hyper-responsiveness, particularly in the S-SNP group. In OVA/SNPs asthma models, OVA with SNP-treated group showed significant airway inflammation, more than those treated with only OVA and without SNPs. In these models, the P-SNP group induced lower levels of inflammation on airways than both the S-SNP or M-SNP groups. Interleukin (IL)-5, IL-13, IL-1beta and interferon-gamma levels correlated with airway inflammation in the tested models, without statistical significance. In the mouse models studied, increased airway inflammation was associated with acute SNPs exposure, whether exposed solely to SNPs or SNPs in conjunction with OVA. P-SNPs appear to be relatively safer for clinical use than S-SNPs and M-SNPs, as determined by lower observed toxicity and airway system inflammation.

Profiles of IgE Sensitization to Der f 1, Der f 2, Der f 6, Der f 8, Der f 10, and Der f 20 in Korean House Dust Mite Allergy Patients

PURPOSE: Measurement of IgE specific to purified house dust mite (HDM) allergens may improve allergy diagnosis. This study aimed to investigate the sensitization profiles of Korean HDM allergic subjects suffering from respiratory allergy and atopic dermatitis (AD) to Der f 1, Der f 2, Der f 6, Der f 8, Der f 10, and Der f 20. METHODS: Recombinant HDM allergens were produced in Pichia pastoris (Der f 1) or Escherichia coli (5 allergens). IgE reactivity to the individual recombinant allergens and total extract of mite was assessed by ELISA. RESULTS: Der f 1 was recognized by 79.1%, Der f 2 by 79.1%, Der f 6 by 9.3%, Der f 8 by 6.2%, Der f 10 by 6.2%, and Der f 20 by 6.6% of the patients' sera tested, while the prevalence of IgE reactivity to total mite extract was 94.7%. Combination of Der f 1 and Der f 2 had a sensitivity of 87.6%. Specific IgE to Der f 2 alone was detected from 89.4% of HDM-sensitized respiratory allergy subjects and 92.3% to the combination of the 2 major allergens Der f 1 and Der f 2. However, sera from fewer patients with AD, namely 72.4% and 71.0%, recognized Der f 1 and Der f 2, respectively. The combination of 2 major allergens allowed diagnosis of 84.5% of the AD patients. No correlation between sensitization to specific allergens and HDM allergy entity was found. CONCLUSIONS: Der f 2 was the most frequently sensitized allergen among the HDM-sensitized respiratory and AD patients in Korea, and the combination of the group 1 and 2 major allergens increased the diagnostic sensitivity. Minor allergens did not significantly improve diagnostic sensitivity. However, further studies are needed to analyze the relationship between sensitization to other HDM allergens and the disease entity of the HDM allergy.

The Time When the Metabolic Compensation for Hypercapnia Begin to Occur in Very Low Birth Weight Infants

PURPOSE: Lung injury from mechanical ventilation is one of the major pathogenetic factors of bronchopulmonary dysplasia. Permissive hypercapnia (PH) is one of the strategies for reducing lung injury. However, PH is frequently infeasible in very low birth weight infants (VLBWI) due to their immature renal compensation for respiratory acidosis. The purpose of this study was to identify time when metabolic compensation for hypercapnia begin to occur in VLBWIs. METHODS: Data were retrospectively collected from 82 VLBWI who were admitted to Seoul National University Bundang Hospital from January 2011 to December 2012. The postnatal day when the difference between actual bicarbonate and expected bicarbonate levels became less than 2.0 mmol/L consistently for the first time under hypercapnea (>40 mmHg) was defined as the time when metabolic compensation for hypercapnea occurred. RESULTS: Metabolic compensation for hypercapnea occurred on 9.1+/-3.9 postnatal day. The younger the gestational age (GA) was and the smaller the birth weight was, the later metabolic compensation for hypercapnea occurred. Late metabolic compensators (> or =9 days) were significantly younger in GA (P=0.001), lighter at birth (P=0.041), intubated longer (P=0.002), and less frequently afflicted with respiratory distress syndrome (P=0.036) compared to early metabolic compensators (<9 days). However, logistic regression analysis revealed only young GA was associated with late metabolic compensation with marginal significance (P=0.068). CONCLUSION: Metabolic compensation for hypercapnea occurred 9 days after birth on average. PH strategy for reducing lung injury should be considered after renal metabolic compensation for hypercapnea occurs in VLBWI.

Human salivary gland stem cells ameliorate hyposalivation of radiation-damaged rat salivary glands

Salivary function in mammals may be defective for various reasons, such as aging, Sjogren's syndrome or radiation therapy in head and neck cancer patients. Recently, tissue-specific stem cell therapy has attracted public attention as a next-generation therapeutic reagent. In the present study, we isolated tissue-specific stem cells from the human submandibular salivary gland (hSGSCs). To efficiently isolate and amplify hSGSCs in large amounts, we developed a culture system (lasting 4-5 weeks) without any selection. After five passages, we obtained adherent cells that expressed mesenchymal stem cell surface antigen markers, such as CD44, CD49f, CD90 and CD105, but not the hematopoietic stem cell markers, CD34 and CD45, and that were able to undergo adipogenic, osteogenic and chondrogenic differentiation. In addition, hSGSCs were differentiated into amylase-expressing cells by using a two-step differentiation method. Transplantation of hSGSCs to radiation-damaged rat salivary glands rescued hyposalivation and body weight loss, restored acinar and duct cell structure, and decreased the amount of apoptotic cells. These data suggest that the isolated hSGSCs, which may have characteristics of mesenchymal-like stem cells, could be used as a cell therapy agent for the damaged salivary gland.

Expression of Maspin Protein in Ductal Hyperplasia, Intraductal Carcinoma and Invasive Ductal Carcinoma of the Breast

Maspin is a recently described gene with tumor suppressor activity. The gene product is a 42 kD protein with homology to the serpin family of protease inhibitors and may play a role as an inhibitor of tumor cell invasion. The prior observation that invasive breast cancers and their metastases showed decreased maspin protein expression by immunostaining supports this speculation. However, the role of maspin in breast cancer progression has not been studied in detail. We, therefore, studied maspin protein expression in a series of hyperplasia, atypical ductal hyperplasia, intraductal carcinoma and invasive carcinomas. Immunohistochemical staining (IHC) for maspin was performed on paraffin sections of 136 breast specimens using a commercially available monoclonal antibody. Among the 106 cases studied were 36 moderate/florid ductal hyperplasia, 11 atypical ductal hyperplasia (ADH), 29 intraductal carcinoma (IDC) (4 low grade, 13 intermediate grade, 12 high grade) and 30 invasive ductal carcinomas. Thirty cases of normal breast were also studied as control group. IHC stains were scored using a semiquantitative scoring system. The mean IHC scores for maspin for normal, moderate/florid hyperplasia, atypical ductal hyperplasia, intraductal carcinoma, and invasive carcinoma were 5.51 1.30, 7.36 0.72, 3.82 1.60, 4.48 2.69, 3.97 3.30, respectively. These scores for each category were statistically significant (p<0.05), except between ADH and IDC. Maspin protein expression was increased in most cases of moderate/florid hyperplasia, while maspin expression was more heterogeneous in ADH and IDC. In high grade IDC, maspin protein expression was stronger than low and intermediate grade IDC, and this suggests the possibility of a compensatory cellular response against the forces driving further tumor progression. Two thirds of invasive ductal carcinomas expressed maspin protein weakly and focally. All metastatic carcinomas of lymph nodes were negative for maspin. It is possible that high grade IDC with strong maspin expression may represent a subset less likely to progress to invasive cancer. This speculation merits investigation in clinical outcome studies.

Cytologic Features of an Angiosarcoma in Pleural Fluid: A Case Report / 대한세포병리학회지

Angiosarcomas are rare tumors, seen most commonly in the skin and soft tissue of head and neck region. But it has been described in numerous body sites including thyroid, breast, liver, spleen, bone, etc.. Their biological behaviors depend on the microscopic grade, site of origin, and multifocality. We report the unique cytological features of an angiosarcoma in pleural fluid. A 61-year-old woman presented with a 6 month history of dyspnea on exertion and chest pain. Chest computerized tomography(CT) revealed multiple subpleural small nodules in the right lung and widespread air space consolidation and pleural effusion in the left lung. CT of liver revealed multiple small low attenuated lesion. The smears obtained from pleural fluid showed hypocellularity with a hemorrhagic background. The tumor cells were highly pleomorphic oval or spindle in shape and presented singly, in loose groups, in knitted syncytial aggregates, and in acinar pattern. Their nuclei had vesicular chromatin with delineated, thick nuclear membranes and occasionally a large eosinophilic, prominent nucleolus. The cytoplasm was plump, thin or projected in spindly fashion. Almost all tumor cells showed variable sized intracytoplasmic vacuoles and their nuclei were sometimes crescentic by a huge vacuole. Occasional binucleated tumor cells and mitotic figures were present. Cellular debris and streaky materials were identified. Needle biopsy specimen from the pleura revealed anastomosing slit-like spaces lined by pleomorphic tumor cells. The tumor cells showed a strong reactivity for CD31 and vimentin and focal weak reactivity for factor VIII-related antigen.

Bronchus-Associated Lymphoid Tissue Lymphoma

Malignant lymphoma arising from mucosa-associated lymphoid tissue (MALT) represents distinct clinicopathologic features and remains localized for prolonged periods. We report a case of low grade B cell lymphoma of bronchus-associated lymphoid tissue (BALT). A 60-year-old female had a long-standing cough, sputum and intermittent fever for 10 years. In 1984, the chest radiography showed increased hazy density in both upper lungs. Although she had been treated by antituberculous medication under clinical diagnosis, there was no improvement. In 1995, open lung biopsy was carried out. Histologically, it showed massive nodular or diffuse infiltration of centrocyte-like cells in bronchus and parenchyme with pleural invasion. On immunohistochemical stain, they were positive for LN-2 and L26 and negative for UCHL-1, LN-1 and LN-3. In polymerase chain reaction (PCR), Ig heavy chain gene rearrangement was detected. The patient was well for 6 months after the biopsy.

Malignant Mixed Mullerian Tumor Arising from Adenomyosis of Uterus

Malignant mixed mullerian tumor (MMMT) is an unusual tumor composed of malignant epithelial and nonepithelial components in the same lesion and is subdivided into homologous and heterologous types. Epidemiologically, these tumors are associated with prior pelvic irradiation, functioning ovarian lesions, exogenous estrogen therapy and rarely endometriosis. We experienced a case of uterine MMMT which arose from adenomyosis in a 47-year-old woman who had no specific past medical history. The posterior uterine corpus showed a 3.5x3.0x2.0 cm sized, relatively well defined tumor mass within the background of the adenomyosis. The tumor was composed of well differentiated endometrial adenocarcinoma and sarcomatous stroma with foci of rhabdomyosarcomatous differentiation confirmed by immunohistochemical and electron microscopic studies. Through the immunohistochemical study, both the epithelial and nonepithelial components were positive for cytokeratin and it suggested that the sarcomatous area originated from metaplasia of the adenocarcinoma component. From the overall findings, it is regarded as an uterine heterologous MMMT which arose from adenomyosis.

Interdigitating Reticulum Cell Sarcoma of Lymph Node

We report a case of reticulum cell sarcoma in the right cervical lymph node of a 42-year-old male. It was a slowly growing, non-tender movable mass of 8 months duration. Microscopically, the lymph node was effaced by proliferating spindle cells arranged in broad sheets, bands, or fascicular patterns in paracortical area sparing of B-cell region. The tumor component was divided by fibrous band. The individual cells had oval to round or elongated nuclei, with inconspicuous nucleoli and moderate amounts of cytoplasms with indistinct cell borders. Pleomorphic large cells with binucleated, or multinucleated bizarre nuclei with prominent nucleoli, were partly admixed. In immunohistochemical stain, the tumor cell was strong positive for S-100 protein, HLA-DR, Mac387 and weakly positive for Leukocyte common antigen and equivocal for Vimentin. But it was negative for CD21, Ki-1, Desmin, Epithelial membrane antigen and Cytokeratin. These immunohistochemical findings suggested that the neoplastic cell was originated from the interdigitating reticulum cell of lymph node. The patient was treated by radiation therapy, and alive well at 37 months of follow-up.

Syphilitic Granulomatous Pancreatitis: A case report

Syphilitic granulomatous pancreatitis is an extremely rare condition,and can occur in the generalized acquired syphilitic patient in tertiary or secondary phase. The most serious problem with granulomatous pancreatic lesion is clinical or radiological misdiagnosis as cancer. We experienced a case of syphilitic granulomatous pancreatitis arising in 54 year old female patient. She was treated for syphilis 20years ago. But she and her husband are still strong positive to VDRL and TPHA. On abdominal computed tomography and endoscopic pancreatico- duodenography, there was an obstructive mass of low density in the distal common bile duct or pancreatic head. Under the preoperative diagnosis of pancreatic head carcinoma, Whipple's operation was done. On gross examination, the pancreas was fibrotic, and the common bile duct was well preserved without tumor mass. Microscopically, numerous intralobular noncaseating epithelioid cell granulomas with multinucleated giant cells are identified. They surround thick-walled, small to medium sized arteries and involve vascular wall with luminal narrowing or obliteration, which are characteristic findings of the syphilitic granuloma. The remaining parenchyme shows fibrosis, acinar atrophy or destruction with dense infiltration of lymphohistiocytes, plasma cells with granuloma formation. Although the Warthin-Starry stain reveals no spirochetes, the serologic result and pathologic findings are compatible with syphilitic granulomatous pancreatitis.

Fine Needle Aspiration Cytology of Sparganosis / 대한세포병리학회지

Human sparganosis is a rare parasitic disease in which the larval cestode proliferates in the various organs in the body. It usually presents as a subcutaneous or soft- tissue mass. By fine needle aspiration this lesion can be diagnosed with its characteristic cytologic findings. We experienced 3 cases of sparganosis diagnosed by the fine needle aspiration. Aspirates were taken from subcutaneous mass in the abdomen and both thighs respectively. The aspirates showed a portion of body of sparganum with numerous calcospherules, smooth muscles and tegmentat cells. They also revealed granulomas with various inflammatory infiltration of eosinophils, neutrophils, lymphocytes and plasma cells.