PURPOSE: Guinea pig is one of the most suitable animal models for Mycobacterium tuberculosis (M. tb) infection since it shows similarities to pulmonary infection in humans. Although guinea pig shows hematogenous spread of M. tb infection into the whole body, immunological studies have mainly focused on granulomatous tissues in lungs and spleens. In order to investigate the time-course of disease pathogenesis and immunological profiles in each infected organ, we performed the following approaches with guinea pigs experimentally infected with M. tb over a 22-week post-infection period. MATERIALS AND METHODS: We examined body weight changes, M. tb growth curve, cytokine gene expression (IFN-gamma and TNF-alpha), and histopathology in liver, spleen, lungs and lymph nodes of infected guinea pigs. RESULTS: The body weights of infected guinea pigs did not increase as much as uninfected ones and the number of M. tb bacilli in their organs increased except bronchotracheal lymph node during the experimental period. The gene expression of IFN-gamma and TNF-alpha was induced between 3 and 6 weeks of infection; however, kinetic profiles of cytokine gene expression showed heterogeneity among organs over the study period. Histophathologically granulomatous lesions were developed in all four organs of infected guinea pigs. CONCLUSION: Although IFN-gamma and TNF-alpha gene expression profiles showed heterogeneity, the granuloma formation was clearly observed in every organ regardless of whether the number of bacilli increased or decreased. However, this protective immunity was accompanied with severe tissue damage in all four organs, which may lead to the death of guinea pigs.
Animals ; Body Weight ; *Disease Progression ; Female ; Gene Expression ; Gene Expression Regulation ; Guinea Pigs ; Interferon-gamma/genetics/*metabolism ; Kinetics ; Liver/metabolism/pathology ; Lung/metabolism/pathology ; Lymph Nodes/metabolism/pathology ; Mycobacterium tuberculosis ; Spleen/metabolism/pathology ; Tuberculosis/*genetics/pathology ; Tumor Necrosis Factor-alpha/genetics/*metabolism

BACKGROUND: Breast cancer is the one of the commonly diagnosed female cancer in Korea. Numerous factors have been noted to be associated with risk of breast cancer: body mass index, menarche, menopause, family history, pregnancy and delivery, breastfeeding, alcohol use, smoking habits, diet, education and use of oral contraceptives. Little is known about hair minerals in breast cancer patient and about correlation between hair minerals and body mass index. METHODS: We compared hair mineral analysis data of 37 breast cancer subject with age and body mass index-matched normal control data (N = 144) by cross-sectional analysis. All breast cancer patients were newly diagnosed at one Breast Cancer Center in Ajou University and had their hair cut before anti-cancer chemotherapy, and the normal controls (without breast cancer) also had their hair cut for various reasons in out-patient clinics of the Department of Family Practice and Community Health. RESULTS: Breast cancer patients had low calcium, magnesium, and zinc, whereas they had high arsenic, sodium, and potassium compared with the normal controls. Only hair zinc level had significant negative correlation with body mass index (r = -0.705, P < 0.001) in breast cancer patients, not in normal controls. CONCLUSION: We observed the difference of hair mineral patterns in newly diagnosed breast cancer patients compared to normal controls and the correlation between these minerals and body mass index in breast cancer patient. Especially hair zinc concentration was significantly reduced and had significant negative correlation with body mass index in breast cancer patients.
Arsenic ; Body Mass Index ; Breast ; Breast Feeding ; Breast Neoplasms ; Calcium ; Contraceptives, Oral ; Cross-Sectional Studies ; Family Practice ; Female ; Food Habits ; Hair ; Humans ; Korea ; Magnesium ; Menarche ; Menopause ; Minerals ; Outpatients ; Potassium ; Reproductive History ; Smoke ; Smoking ; Sodium ; Zinc

Background: The current conventional drug susceptibility test (DST) for Mycobacterium tuberculosis (Mtb) takes several weeks of incubation to obtain results. As a rapid method, molecular DST requires only a few days to get the results but does not fully cover the phenotypic resistance. A new rapid method based on the ability of viable Mtb bacilli to hydrolyze fluorescein diacetate to free fluorescein with detection of fluorescent mycobacteria by flow cytometric analysis, was recently developed. Methods: To evaluate this cytometric method, we tested 39 clinical isolates which were susceptible or resistant to isoniazid (INH) or rifampin (RIF), or ethambutol (EMB) by phenotypic or molecular DST methods and compared the results. Results: The susceptibility was determined by measuring the viability rate of Mtb and all the isolates which were tested with INH, RIF, and EMB showed susceptibility results concordant with those by the phenotypic solid and liquid media methods. The isolates having no mutations in the molecular DST but resistance in the conventional phenotypic DST were also resistant in this cytometric method. These results suggest that the flow cytometric DST method is faster than conventional agar phenotypic DST and may complement the results of molecular DST. Conclusion In conclusion, the cytometric method could provide quick and more accurate information that would help clinicians to choose more effective drugs.

PURPOSE: To evaluate the diagnostic utility and predictors for determinate results of an enzyme-linked immunospot assay using induced sputum cells (IS ELISPOT) for a rapid diagnosis of pulmonary tuberculosis (TB). MATERIALS AND METHODS: Subjects suspected of pulmonary TB who had either sputum acid fast bacilli smear-negative or not producing sputum spontaneously were prospectively enrolled. ELISPOT assay was performed using cells from induced sputum. RESULTS: A total of 43 subjects, including 25 with TB (TB group) and 18 with non-TB disease (non-TB group) were enrolled. Results of IS ELISPOT were determinate in only 17/43 (39%) subjects, but all of determinate results were consistent with the final diagnosis. Of the 43 sputum samples, 11 (26%) were inadequate to perform IS ELISPOT. Of 32 adequate sputum samples, the proportion of determinate results was significantly higher in the TB group (75%, 15/20) than in the non-TB group (17%, 2/12) (p=0.002). The status of active TB was a unique predictor but smear positivity was not a significant predictor for determinate results. In addition, sensitivity of IS ELISPOT (75%, 9/12) in smear negative TB was higher than that of TB-polymerase chain reaction (25%, 3/12). CONCLUSION: IS ELISPOT showed relatively high diagnostic value and accuracy in the TB group, independent of smear positivity. IS ELISPOT may provide additional diagnostic yield for microbiological tools in the rapid diagnosis of smear-negative TB.
Adult ; Aged ; *Enzyme-Linked Immunospot Assay ; Female ; Humans ; Immunologic Tests/*methods ; Male ; Middle Aged ; Mycobacterium tuberculosis/*isolation & purification ; Predictive Value of Tests ; Prospective Studies ; Reproducibility of Results ; Risk Factors ; Sensitivity and Specificity ; Sputum/*microbiology ; Tuberculosis, Pulmonary/*diagnosis/microbiology

Mental health is influenced by the gut-brain axis; for example, gut dysbiosis has been observed in patients with major depressive disorder (MDD).Gut microbial changes by fecal microbiota transplantation or probiotics treatment reportedly modulates depressive symptoms. However, it remains unclear how gut dysbiosis contributes to mental dysfunction, and how correction of the gut microbiota alleviates neuropsychiatric disorders. Our previous study showed that chronic consumption of Lactobacillus reuteri ATG-F4 (F4) induced neurometabolic alterations in healthy mice. Here, we investigated whether F4 exerted therapeutic effects on depressive-like behavior by influencing the central nervous system. Using chronic unpredictable stress (CUS) to induce anhedonia, a key symptom of MDD, we found that chronic F4 consumption alleviated CUS-induced anhedonic behaviors, accompanied by biochemical changes in the gut, serum, and brain. Serum and brain metabolite concentrations involved in tryptophan metabolism were regulated by CUS and F4. F4 consumption reduced the elevated levels of serotonin (5-HT) in the brain observed in the CUS group. Additionally, the increased expression of Htr1a, a subtype of the 5-HT receptor, in the medial prefrontal cortex (mPFC) of stressed mice was restored to levels observed in stress-naïve mice following F4 supplementation. We further demonstrated the role of Htr1a using AAV-shRNA to downregulate Htr1a in the mPFC of CUS mice, effectively reversing CUS-induced anhedonic behavior. Together, our findings suggest F4 as a potential therapeutic approach for relieving some depressive symptoms and highlight the involvement of the tryptophan metabolism in mitigating CUS-induced depressive-like behaviors through the action of this bacterium.

PURPOSE: The incidence rate and the mortality rate of gastric cancer have decreased in developed countries over the last several decades. On the other hand, they remain high in far eastern countries such as Korea, Japan, China and in many developing countries. The cure of patients with gastric carcinomas can be achieved mostly through complete surgical resection, but most gastric cancer patients are in advanced stages when diagnosed and have poor prognoses. therefore, the development of an effective systemic therapy is essential for far advanced gastric cancer patients. Until recently, the most commonly used combination chemotherapy was based on 5-flurouracil or cisplatin, but the results were not satisfactory, so recently etoposide, adriamycin and cisplatin (EAP-II) combination chemotherapy was introduced in patients with advanced gastric cancer. Early studies showed a high response rate and the ability to convert unresectable cases to resectable ones, but later studies couldn`t duplicate the result. the purpose of this study was to evaluate the relative efficacy&toxicity of EAP-II chemotherapy and ELF chemotherapy which is based on 5-flurouracil. MATENRIALS AND METHODS: Between July 1992 and July 2002, sixty-five patients with inoperable advanced gastric cancer were enrolled for this study. Thirty-seven patient received EAP-II chemotherapy:etoposide (20 mg/m2 IV for 1~5 days), adriamycin (20 mg/m2 IV for 1~5 days) and cisplatin (20 mg/m2 IV for 1~5 days) and Twenty-eight patients receieved ELF chemotherapy:etoposide (100 mg/m2 IV for 1~3 days), leucovorin (20 mg/m2 IV for 1~5 days) and 5-FU (500 mg/m2 IV for 1~5 days). Each treatment schedule for each group was repeated every four weeks: EAP-II means 3.4 cycles per patient: ELF means 4.1 cycles per patient RESULTS: Total respones rates were 5.4% in the ELF group and 3.6% in the EAP group (P-value>0.05). The median times to progression were 144 days in the ELF group and 92 days in the EAP-II group (P-value>0.05), and the median overall survival times were 189 days in the ELF group and 139 days in the EAP-II group (P-value>0.05). The difference in the survival curves for the two regimens was not statistically significant. Non-hematologic toxicitis&hematologic toxicitis were more frequently observed for the EAP-II regimen. Anemia: 27.6% in ELF vs 54% in EAP-II; Leukopenia: 8.5% in ELF vs 19% in EAP-II; nausea&vomiting: 45.9% in ELF vs 67.8% in EAP-II. CONCLUSION: EAP-II regimen is not superior to ELF regimen in the tratment of inoperable advanced gastric cancer.
Anemia ; Appointments and Schedules ; China ; Cisplatin ; Developed Countries ; Developing Countries ; Doxorubicin* ; Drug Therapy ; Drug Therapy, Combination ; Etoposide* ; Fluorouracil ; Hand ; Humans ; Incidence ; Japan ; Korea ; Leucovorin* ; Leukopenia ; Mortality ; Prognosis ; Retrospective Studies* ; Stomach Neoplasms*

PURPOSE: The incidence rate and the mortality rate of gastric cancer have decreased in developed countries over the last several decades. On the other hand, they remain high in far eastern countries such as Korea, Japan, China and in many developing countries. The cure of patients with gastric carcinomas can be achieved mostly through complete surgical resection, but most gastric cancer patients are in advanced stages when diagnosed and have poor prognoses. therefore, the development of an effective systemic therapy is essential for far advanced gastric cancer patients. Until recently, the most commonly used combination chemotherapy was based on 5-flurouracil or cisplatin, but the results were not satisfactory, so recently etoposide, adriamycin and cisplatin (EAP-II) combination chemotherapy was introduced in patients with advanced gastric cancer. Early studies showed a high response rate and the ability to convert unresectable cases to resectable ones, but later studies couldn`t duplicate the result. the purpose of this study was to evaluate the relative efficacy&toxicity of EAP-II chemotherapy and ELF chemotherapy which is based on 5-flurouracil. MATENRIALS AND METHODS: Between July 1992 and July 2002, sixty-five patients with inoperable advanced gastric cancer were enrolled for this study. Thirty-seven patient received EAP-II chemotherapy:etoposide (20 mg/m2 IV for 1~5 days), adriamycin (20 mg/m2 IV for 1~5 days) and cisplatin (20 mg/m2 IV for 1~5 days) and Twenty-eight patients receieved ELF chemotherapy:etoposide (100 mg/m2 IV for 1~3 days), leucovorin (20 mg/m2 IV for 1~5 days) and 5-FU (500 mg/m2 IV for 1~5 days). Each treatment schedule for each group was repeated every four weeks: EAP-II means 3.4 cycles per patient: ELF means 4.1 cycles per patient RESULTS: Total respones rates were 5.4% in the ELF group and 3.6% in the EAP group (P-value>0.05). The median times to progression were 144 days in the ELF group and 92 days in the EAP-II group (P-value>0.05), and the median overall survival times were 189 days in the ELF group and 139 days in the EAP-II group (P-value>0.05). The difference in the survival curves for the two regimens was not statistically significant. Non-hematologic toxicitis&hematologic toxicitis were more frequently observed for the EAP-II regimen. Anemia: 27.6% in ELF vs 54% in EAP-II; Leukopenia: 8.5% in ELF vs 19% in EAP-II; nausea&vomiting: 45.9% in ELF vs 67.8% in EAP-II. CONCLUSION: EAP-II regimen is not superior to ELF regimen in the tratment of inoperable advanced gastric cancer.
Anemia ; Appointments and Schedules ; China ; Cisplatin ; Developed Countries ; Developing Countries ; Doxorubicin* ; Drug Therapy ; Drug Therapy, Combination ; Etoposide* ; Fluorouracil ; Hand ; Humans ; Incidence ; Japan ; Korea ; Leucovorin* ; Leukopenia ; Mortality ; Prognosis ; Retrospective Studies* ; Stomach Neoplasms*

Background: Controlled-release oxycodone/naloxone (OXN-CR) maintains the effect of opioid-induced analge-sia through oxycodone while reducing the occurrence rate of opioid-induced constipation through naloxone. The present study was designed to assess the non-inferiority of OXN-CR to controlled-release oxycodone (OX-CR) for the control of cancer-related pain in Korean patients. Methods: In this randomized, open-labeled, parallel-group, phase IV study, we enrolled patients aged 20 years or older with moderate to severe cancer-related pain [numeric rating scale (NRS) pain score≥4] from seven Korean oncology/hematology centers. Patients in the intention-to-treat (ITT) population were randomized (1:1) to OXN-CR or OX-CR groups. OXN-CR was administered starting at 20 mg/10 mg per day and up-titrated to a maximum of 80 mg/40 mg per day for 4 weeks, and OX-CR was administered starting at 20 mg/day and up-titrated to a maximum of 80 mg/day for 4 weeks. The primary efficacy endpoint was the change in NRS pain score from baseline to week 4, with non-inferiority margin of?1.5. Secondary endpoints included analgesic rescue medication intake, patient-reported change in bowel habits, laxative intake, quality of life (QoL), and safety assessments. Results: Of the ITT population comprising 128 patients, 7 with missing primary efficacy data and 4 who violated the eligibility criteria were excluded from the efficacy analysis. At week 4, the mean change in NRS pain scores was not significantly different between the OXN-CR group (n= 58) and the OX-CR group (n= 59) (?1.586 vs.?1.559, P= 0.948). The lower limit of the one-sided 95％ confidence interval (?0.776 to 0.830) for the difference exceeded the non-inferiority margin (P < 0.001). The OXN-CR and OX-CR groups did not differ significantly in terms of analgesic rescue medication intake, change in bowel habits, laxative intake, QoL, and safety assessments. Conclusions: OXN-CR was non-inferior to OX-CR in terms of pain reduction after 4 weeks of treatment and had a similar safety profile. Studies in larger populations of Korean patients with cancer-related pain are needed to further investigate the effectiveness of OXN-CR for long-term pain control and constipation alleviation.