The aim of the present study was the evaluation of possible protective effects of exercise against β-cell damage in streptozotocin (STZ)-induced diabetes in rats. The animals were divided into five groups: the control group, the STZ-induced diabetes group, the STZ-induced diabetes and light-intensity exercise group, the STZ-induced diabetes and moderate-intensity exercise group, and the STZ-induced diabetes and heavy-intensity exercise group. Animals in the exercise groups were made to swim one of three exercise protocols once a day for 12 consecutive weeks. STZ was injected intraperitoneally at a single dose of 50 mg/kg for diabetes induction. Exercise training was continued for 4 weeks prior to STZ administration; these applications were continued end of the study (for 12 weeks). Erythrocyte and pancreatic tissue malondialdehyde (MDA) levels and serum nitric oxide (NO) concentration were measured. Moreover glutathione peroxidase (GSHPx), superoxide dismutase (SOD) and catalase (CAT) were also measured in pancreatic homogenates. Pancreatic β-cells were examined by immunohistochemical methods. STZ increased lipid peroxidation and decreased the antioxidant enzyme activity significantly. Exercise, especially moderate-intensity exercise has shown protective effect probably through decreasing lipid peroxidation and increasing antioxidant enzyme activity. Islet cell degeneration and weak insulin immunohistochemical staining were observed in STZ induced diabetic rats. Increased intensity of staining for insulin and preservation of β-cell numbers were apparent in the exercise-applied diabetic rats. Interestingly, the best result was obtained from moderate-intensity exercise. These findings suggest that exercise has a therapeutic and/or protective effect in diabetes by decreasing oxidative stress and preservation of pancreatic β-cell integrity.
In order to determine the appropriate treatment of malignant lymphoma, it is important to know the degree to which extra-nodal invasion of lymphoma cells has occurred. We amplified complementarity-determining region (CDR) III genes in 64% of lymph node samples at the onset or relapse of B-cell-lineage non-Hodgkin’s lymphoma (NHL) in 22 patients. By using a clone-specific CDR III probe in each patient, we were able to detect minimal residual disease (MRD) of lymphoma cells in the bone marrow and/or blood in 9 out of 14 cases (64.2%) at the onset of the disease or relapse, whereas abnormal cells in the bone marrow and/or blood were identified by routine morphological analysis in only 4 out of 22 cases (18.2%). This indicates that extranodal invasion of malignant cells may be common in patients with NHL. In some cases, the clone-specific CDR III gene was still expressed in the samples of bone marrow and/or peripheral blood even after chemotherapy, when other markers associated with NHL were no longer expressed. Five out of six cases in this group had a worse outcome associated with NHL. On the other hand, most of the cases whose clone-specific CDR III gene was no longer expressed in the bone marrow and/or in circulation after treatment had a relatively fair prognosis. These results indicate that the detection at molecular level of MRD in extranodal organs may prove useful as a predictor of prognosis for NHL.
Interictal spikes in patients with epilepsy may be detected by either electroencephalography (EEG) (E-spikes) or magnetoencephalography (MEG) (M-spikes), or both MEG and EEG (E/M-spikes). Localization and amplitude were compared between E/M-spikes and M-spikes in 7 adult patients with extratemporal epilepsy to evaluate the clinical significance of MEG spikes. MEG and EEG were simultaneously measured using a helmet-shaped MEG system with planar-type gradiometers and scalp electrodes of the international 10-20 system. Sources of E/M-spikes and M-spikes were estimated by an equivalent current dipole (ECD) model for MEG at peak latency. Each subject showed 9 to 20 (mean 13.4) E/M-spikes and 9 to 31 (mean 16.3) M-spikes. No subjects showed significant differences in the ECD locations between E/M- and M-spikes. ECD moments of the E/M-spikes were significantly larger in 2 patients and not significantly different in the other 5 patients. The similar localizations of E/M-spikes and M-spikes suggest that combination of MEG and EEG is useful to detect more interictal spikes in patients with extratemporal epilepsy. The smaller tendency of ECD amplitude of the M-spikes than E/M-spikes suggests that scalp EEG may overlook small tangential spikes due to background brain noise. Localization value of M-spikes is clinically equivalent to that of E/M-spikes.
Various processed foods and beverages have been manufactured using deep seawater (DSW), desalted DSW (dDSW), and concentrated DSW in Japan. To confirm the safety of dDSW, we investigated hematologic and blood chemical effects of dDSW in mice. The dDSW and desalted surface seawater (dSSW) were diluted to 6.7%, 10%, and 20% with purified water. BALB/c mice were housed for 12 weeks, and administered the diluted dDSW, dSSW, or purified water as a control during the period. The results for dDSW were compared with those for dSSW and purified water. None of the groups of mice showed any clear abnormal growth or behavior; neither did any show signs of illness nor a single case of death during the 12 weeks study. We found no significant differences between the dDSW and control groups in terms of red blood cell count, hemoglobin, hematocrit, white blood cell count, and neutrophil counts, whereas white blood cell and lymphocyte counts were significantly higher in the 10% dSSW group at the end of 4 and 12 weeks than those in the control group. A significantly higher triglyceride level was detected only in the 6.7% dSSW group. Our results show no evidence of acute or subacute effects of diluted dDSW. Effects of diluted dDSW on hematologic and blood chemical values in mice are thought to be similar to those of purified water. This finding suggests that dDSW is as safe as purified water for drinking water.
Hyperthyroidism is characterized by accelerated bone turnover, caused from direct stimulation of bone cells by increased thyroid hormones. In this study, we aimed to investigate serum osteocalcin levels as a bone formation marker, before antithyroid (propylthiouracil) therapy at hyperthyroid stage and after antithyroid therapy at euthyroid stage of the patients. Twenty four hyperthyroid patients (18 females, 6 males) and 20 (13 females, 7 males) healthy controls were included into this study. Blood and urine samples were taken before medical treatment at hyperthyroid state, and after the antithyroid therapy until the patients reached the euthyroid state. Serum alkaline phosphatase, osteocalcin, calcium, phosphorus, Free T3, Free T4, TSH and urine calcium/creatinine levels were assessed. We found a significant decrease in serum osteocalcin (p=0.006), urinary calcium/creatinine (p=0.004), and serum phosphorus (p=0.038) levels in euthyroid state in comparison to hyperthyroid state. The increases in serum bone formation marker osteocalcin and bone resorption marker urinary calcium/creatinine levels in hyperthyroid state compared to euthyroid state in our study confirmed that hyperthyroid patients have high bone turnover. We conclude that, hyperthyroid patients has high bone turnover of formation and resorption even after attainment of euthyroidism. Osteocalcin and urine calcium/creatinine are sensitive markers in documenting bone remodeling during treatment of hyperthyroidism.
The health-related QOL (HRQOL) has been used extensively in clinical and epidemiological research and health service studies. Especially, the Medical Outcome Study Short-form 36-Item Health Survey (SF-36) is a widely used health status measure. However, a Korean version has not been developed and tested yet. The purpose of this study was to develop a Korean version of the Short-form Health Survey (SF-36) for use in health related quality of life measurements for Korean elderly people. SF-36 data from 90 healthy elderly people using Social Education Service and 120 elderly patients using a day care service in Seoul, Korea, were examined. We translated SF-36 version 2.0 into Korean and assessed its reliability and validity. In the results, the content validity and discriminant validity were found to be satisfactory. Cronbach’s α coefficients ranged from 0.9298 to 0.9383. The test-retest reliability coefficients ranged from 0.710 to 0.895. In addition, the utility was examined by testing the correlation between the health-related QOL and related factors (sex, age, motor function, ability of daily life) among the elderly people. The present findings suggested that the Korean version of SF-36 would be useful as a measure of the health related QOL in Korean elderly people.
This study aims to clarify the effects of stress perception and related social indicators on three major musculoskeletal symptoms: low back, shoulder, and joint pains in a Japanese population. Twenty health-related variables (stress perception and 19 social indicators) and the three symptoms were obtained from the following Japanese national surveys: the Comprehensive Survey of Living Condition of the People on Health and Welfare, the System of Social and Demographic Statistics of Japan, and the Statistical Report on Health Administration Services. The results were compared among 46 Japanese prefectures in 1995 and 2001. By factor analysis, the 19 indicators were classified into three factors of urbanization, aging and life-regularity, and individualization. The prevalence of stress perception was significantly correlated to the 8 indicators of urbanization factor. Although simple correlation analysis revealed a significant relationship of stress perception only to shoulder pain (in both years) and low back pain (in 2001), the results of multiple regression analysis showed that stress perception and some urbanization factors were significantly associated with all the three symptoms in both years exclusive of joint pain in 1995. Taking the effects of urbanization into consideration, stress perception seems to be closely related to the complaints of musculoskeletal symptoms in Japan.
Single-agent paclitaxel has been shown to be effective as both first- and second-line treatment of metastatic breast cancer, and the efficacy and tolerability of weekly administration of paclitaxel has generated much interest. Fifty-two patients with pretreated metastatic breast cancer who were admitted to Hacettepe University between January 2001 and June 2002 were retrospectively analyzed in this study. Paclitaxel was administered weekly in a dose of 80 mg/m2 over 1 hour. The median number of cycles delivered was 20 weeks (range, 8 to 24). The median delivered dose was 2400 mg (range, 960 to 3840 mg). At a median follow-up of 12.3 months (range, 6 to 17), all patients were assessable for response and toxicity. A complete response and partial response were observed in 7 (13.5%), and 19 (36.5%) patients, respectively. Overall response rate was 50%. Median duration of response was 10 months (range, 3 to 16). Therapy was generally well tolerated, and toxicities were manageable. Severe leukopenia was seen in two (4%) patients. Based on these results, we conclude that weekly paclitaxel is a well-tolerated and highly effective regimen in pre-treated metastatic breast cancer.
We investigated lipid peroxidation, resistance of plasma and red blood cells to oxidation, and antioxidant defense system in erythrocytes and sera in patients with type 2 diabetes mellitus. One group included newly diagnosed 20 patients and the other included 20 patients treated with oral antidiabetic agents (OAD). Twenty healthy subjects served as controls. Serum and red blood cell malondialdehyde (MDA), glutathione (GSH), resistance to oxidation, and plasma thiol (total -SH) levels were measured. In addition, glycated hemoglobin, serum fructosamine, uric acid, total protein, total cholesterol, triglyceride and glucose levels were determined. Although newly diagnosed patients had higher serum and erythrocyte MDA levels than those of controls, the highest levels of MDA were determined in patients treated with OAD. MDA levels after exposing to oxidation increased in OAD group more than in newly diagnosed patients. Total -SH and erythrocyte GSH levels of the both diabetic groups were lower than controls. These results show that serum and erythrocyte lipid peroxidation was increased in diabetic patients. The sera of the patients showed a decreased resistance against oxidation. We therefore suggest that the effect of increased free radicals may be prevented by antioxidant systems in early stages of type 2 diabetes but in advanced stages this relationship is impaired owing to decreased antioxidant activity. Decreased red blood cell GSH and serum total -SH levels may be due to a compensation mechanism of the antioxidants.
Acute hypoxia produces an increase in ventilation. When the hypoxia is sustained, the initial increase in ventilation is followed by a decrease in ventilation. Hypoxia causes changes in brain neurotransmitters depending on its severity and durations. The purpose of this study was to investigate the role of gamma-aminobutyric acid (GABA) and glutamate for hypoxic ventilatory response in rabbits. The experiments were performed in peripheral chemoreceptors intact and denervated rabbits anesthetized with Na-pentobarbitate. For intracerebroventricular (ICV) injections of reagents in each animal, cannula was placed in left lateral cerebral ventricle by stereotaxic method. After ICV injection of GABA (0.48 mg/kg), air breathing in both groups caused a depression of respiratory activity. On the other hand, after ICV injection of GABA, breathing of hypoxic gas mixture (8% O2-92% N2) in both groups produced the hypoxic hyperventilation. After ICV injection of GABA, blockade of GABAA receptors with bicuculline (0.2 mg/kg) did not prevent the hypoxic hyperventilation. In contrast, after ICV GABA injection, blockade of glutamate NMDA receptors with MK-801 (0.09 mg/kg) completely abolished the hypoxic hyperventilation observed while the animals were breathing hypoxic gas mixture. Our findings suggest that ICV injection of GABA causes respiratory depression in normoxic conditions, and that it increases ventilation in hypoxic conditions with or without peripheral chemoreceptor impulses by increasing glutamate.