OBJECTIVES: The antimicrobial activity of silver nanoparticles has resulted in their widespread use in many consumer products. Yet, despite their many advantages, it is also important to determine whether silver nanoparticles may represent a hazard to the environment and human health. METHODS: Thus, to evaluate the genotoxic potential of silver nanoparticles, in vivo genotoxicity testing (OECD 474, in vivo micronuclei test) was conducted after exposing male and female Sprague-Dawley rats to silver nanoparticles by inhalation for 90 days according to OECD test guideline 413 (Subchronic Inhalation Toxicity: 90 Day Study) with a good laboratory practice system. The rats were exposed to silver nanoparticles (18 nm diameter) at concentrations of 0.7 x 10(6) particles/cm3 (low dose), 1.4 x 10(6) particles/cm3 (middle dose), and 2.9 x 10(6) particles/cm3 (high dose) for 6 hr/day in an inhalation chamber for 90 days. The rats were killed 24 hr after the last administration, then the femurs were removed and the bone marrow collected and evaluated for micronucleus induction. RESULTS: There were no statistically significant differences in the micronucleated polychromatic erythrocytes or in the ratio of polychromatic erythrocytes among the total erythrocytes after silver nanoparticle exposure when compared with the control. CONCLUSION: The present results suggest that exposure to silver nanoparticles by inhalation for 90 days does not induce genetic toxicity in male and female rat bone marrow in vivo.
Animals ; Bone Marrow ; Erythrocytes ; Female ; Femur ; Humans ; Inhalation ; Inhalation Exposure ; Male ; Mutagenicity Tests ; Nanoparticles ; Rats ; Rats, Sprague-Dawley ; Silver

Adenosquamous carcinomas of the intestine are rare tumors, especially when they occur in the small bowel. We report a case of primary adenosquamous carcinoma of the proximal jejunum in a 66 year old woman with no underlying pathologic condition. The tumor mainly consisted of well differentiated squamous cell carcinoma showing keratin pearl and conspicuous intercellular bridges, and minor portion revealed well differentiated adenocarcinoma. The tumor seemed to have originated from the mucosal epithelium, invading the entire wall and metastasizing to the regional lymph nodes. Previous reports of adenosquamous carcinoma of the small intestine have been associated with metastatic disease from distant sites or intestinal duplication. In the colon, squamous cell differentiation have been seen in about 0.05% of adenocarcinomas and in 0.4% of adenomata. The pathogenesis of squamous cell carcinoma of the intestine is unknown, but some possible mechanisms are proposed. :1)malignant transformation of squamous cell epithelium in the submucosa, 2)aberrant differentiation of stem cells to squamous cell with subsequent malignant change, 3)squamous metaplasia of glandular cells with subsequent malignant change, 4)transformation of an adenosquamous into an epidermoid carcinoma.
Adenocarcinoma ; Aged ; Carcinoma, Adenosquamous* ; Carcinoma, Squamous Cell ; Cell Differentiation ; Colon ; Epithelium ; Female ; Humans ; Intestine, Small ; Intestines ; Jejunum* ; Lymph Nodes ; Metaplasia ; Stem Cells

OBJECTIVES: We have investigated the toxic effects of the inhalation of subchronic and acute levels of n-octane. METHODS: The rats were exposed to n-octane of 0, 2.34, 11.68 and 23.36 mg/L (n = 5 rats/group/gender) in an acute inhalation test (Organization for Economic Co-operation and Development (OECD) TG 403), or to 0, 0.93, 2.62 and 7.48 mg/L (n = 10 rats/group/gender) for a subchronic inhalation test (OECE TG 413), to establish a national chemical management system consistent with the Globally Harmonized Classification System (GHS). RESULTS: Acutely-exposed rats became lethargic but recovered following discontinuation of inhalation. Other clinical symptoms such as change of body weight and autopsy finds were absent. The LC50 for the acute inhalation toxicity of n-octane was determined to exceed 23.36 mg/L and the GHS category was 'not grouping'. Subchronically-treated rats displayed no significant clinical and histopathological differences from untreated controls; also, target organs were affected hematologically, biochemically and pathologically. Therefore, the no observable adverse effect level was indicated as exceeding 7.48 mg/L and the GHS category was 'not grouping' for the specific target organ toxicity upon repeated exposure. CONCLUSION: However, n-octane exposure should be controlled to be below the American Conference of Industrial Hygienists recommendation (300 ppm) to prevent inhalation-related adverse health effects of workers.
Animals ; Autopsy ; Body Weight ; Inhalation ; Octanes ; Rats

BACKGROUND: The neuromuscular blocker is helpful to intubate the patients and reduce the amount of anesthetic agent. It also used at intensive care unit (ICU) to maintain airway patency, to achieve proper ventilatory care, etc. This survey is to determine the neuromuscular blocker usage patterns in ICU settings. METHODS: Three hundred general hospitals with ICU settings were chosen. We designed a 10 itemed questionnaire which has several subquestions with multiple choices and sent it to them. After three months, forty seven hospitals returned the questionnaire and we made careful analysis with it. RESULTS: The most frequent indication of neuromuscular blocker was to facilitate the mechanical ventilation (80.9%). Vecuronium was the most common neuromuscular blocker used (97.9%). Only 6.4% of them used peripheral nerve stimulator and the rest of them (89.4%) used clinical information to determine the degree of neuromuscular blocker. The respondents reported that recovery from muscle relaxation was needed on a periodic basis for regular neurological examinations (59.6%) in ICU settings. All respondents used the sedatives or narcotics with neuromuscular blocker and only 6.4% used reversal agents. CONCLUSIONS: Although the rate of reply was not much (15.7%), we could get the current usage pattern of neuromuscular blocker at ICU. We recommend using short to intermediate acting neuromuscular blocker than long acting agents. Continuous infusion with careful dosage titration by peripheral nerve stimulator would be helpful to achieve rapid recovery. Additional sedatives and narcotics are beneficial to reduce the amount of neuromuscular blocker and to make patients comfortable as well.
Surveys and Questionnaires ; Hospitals, General ; Humans ; Hypnotics and Sedatives ; Intensive Care Units* ; Critical Care* ; Muscle Relaxation ; Narcotics ; Neurologic Examination ; Neuromuscular Blockade* ; Peripheral Nerves ; Surveys and Questionnaires ; Respiration, Artificial ; Vecuronium Bromide

Pure red cell aplasia(PRCA) is characterized by anemia, absence of reticulocytes in the peripherial blood and selective erythroid hypoplasia in the bone marrow. Acquired PRCA is often associated with thymoma but may also occur in many diverse conditions, such as chromic lymphocytic leukemia, systemic lupus erythematosus, autoimmune disorders, T gamma lymphocytosis, acquired hypogammaglobulinemia, acquired immunodeficiency syndrome. Recently we experienced a case of T cell chronic lymphocytic leukemia associated with pure red cell aplasia. A 65-year-old man was presented with severe anemia. absolute reticulocytopenia, hepatosplenomegaly and lymphocytosis(T cell marker' CD2, CD7 positive). Bone marrow findings showed a marked decrease in erythroid precursors and normal maturations of granulocytic and megakaryocytic series, which were consistent with pure red cell aplasia. So we report this case with a review of the literature.
Acquired Immunodeficiency Syndrome ; Aged ; Anemia ; Bone Marrow ; Common Variable Immunodeficiency ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell* ; Leukemia, Lymphoid ; Lupus Erythematosus, Systemic ; Lymphocytosis ; Red-Cell Aplasia, Pure* ; Reticulocytes ; Thymoma

BACKGROUND: The increasing rate of drug-resistant tuberculosis (TB) is a threat to the public health and TB control. In Korea, about 75~80% of TB patients are treated in private hospitals and the rate has been continuously increasing since 2000. METHODS: On a retrospective basis, we enrolled 170 newly diagnosed with or retreated for multidrug-resistant TB (MDR-TB) in 2004 from 21 private hospitals. We extracted the following demographics and treatment history from patient medical records: initial treatment outcomes, cumulative survival rates, treatment outcomes, and prognostic factors. RESULTS: Of the 170 patients, the majority were male (64.1%), the mean age was 44.5 years old, and mean body-mass-index was 20.2 kg/m2. None of the patients tested positive for HIV. Eleven (6.5%) were confirmed to have extensively drug-resistant TB (XDR-TB) at treatment initiation. Treatment success rates were not different between XDR-TB (36.4%, 4/11) and non-XDR MDR-TB (51.6%, 82/159). Default rate was high, 21.8% (37/170). Far advanced disease on X-ray was a significant negative predictor of treatment success; advanced disease and low BMI were risk factors for all-cause mortality. CONCLUSION: In private hospitals in Korea, the proportion of XDR-TB in MDR-TB was comparable to previous data. The treatment success rate of MDR-/XDR-TB remains poor and the failure rate was quite high. Adequate TB control policies should be strengthened to prevent the further development and spread of MDR-/XDR-TB in Korea.
Demography ; Extensively Drug-Resistant Tuberculosis ; HIV ; Hospitals, Private ; Humans ; Korea ; Male ; Public Health ; Retrospective Studies ; Risk Factors ; Survival Rate ; Tuberculosis, Multidrug-Resistant

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.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.