Protective Effect of Melatonin on Methamphetamine-Induced Apoptosis in Glioma Cell Line

Methamphetamine (METH) is a highly addictive drug causing neurodegenerative diseases. METH has been known to be neurotoxic by inducing oxidative stress, free radical, and pro-inflammatory cytokines. Previous studies have shown that METH could induce neuron and glial cell death, especially inducing glial cell-mediated neurotoxicity that plays a critical role in stress-induced central nervous system damage. Therefore, the aim of the present study is to explore the mechanisms of METH-induced cell death in the glial cell. METH-induced glial cells death is mediated via mitochondrial damage pathway. METH activates the upregulation of the Bax, cytochrome c, cleavage caspase 9 and 3 proteins, and downregulation of Bcl-X_L protein in cascade. Pretreatment with melatonin, a neurohormone secreted by the pineal gland, effectively reduced glial cell death. Moreover, melatonin increased the Bcl-X_L/Bax ratio but reduced the level of cytochrome c, cleavage caspase 9 and 3 proteins. Therefore, these results demonstrated that melatonin could reduce the cytotoxic effect of METH by decreasing the mitochondrial death pathway activation in glial cells. This outcome suggests that melatonin might be beneficial as the neuroprotection in neurodegenerative diseases caused by METH or other pathogens.     

Butea superba (Roxb.) improves penile erection in diabetic rats

The objective of the present study was to investigate the effect of ethanolic extract of Butea superba (Roxb.) on erectile dysfunction in diabetic rats by the measurement of intracavernous pressure (ICP) and on cavernosal smooth muscle relaxation. Male Sprague-Dawley rats were induced to become diabetic by a single intravenous injection of Streptozotocin (55 mg kg(-1) body weight). The ethanolic extract at the concentration of 1, 10 and 100 mg kg(-1) BW was administered orally once a day to diabetic rats in each group for 4 weeks. Diabetic rats showed a significant decrease in both ICP and the relaxation of the cavernosal smooth muscle compared with the normal rats. The extract of B. superba significantly increased the ICP with the effective dose of 10 mg kg(-1) BW (61.00 ± 11.11 mmHg versus 39.61 ± 11.01 mmHg in the diabetic control group). Moreover, the B. superba-treated group also showed enhanced relaxation of the cavernosal smooth muscle with EC(50) of 1.17 mg ml(-1). These results suggest that the extract of B. superba enhanced penile erection in diabetic rats by increasing the ICP. This might be explained by the increased blood flow as a result of the relaxation of the cavernous smooth muscle.     

A High‐yield Fall Risk and Adverse Events Screening Questions From the Stopping Elderly Accidents,Death, and Injuries (STEADI) Guideline for Older Emergency Department Fall Patients

Objectives

The objectives were to examine whether responses to the Stopping Elderly Accidents, Death, and Injuries (STEADI) questions responses predicted adverse events after an older adult emergency department (ED) fall visits and to identify factors associated with such recurrent fall.

Methods

We conducted a prospective study at two urban, teaching hospitals. We included patients aged ≥ 65 years who presented to the ED for an accidental fall. Data were gathered for fall‐relevant comorbidities, high‐risk medications for falls, and the responses to 12 questions from the STEADI guideline recommendation. Our outcomes were the number of 6‐month adverse events that were defined as mortality, ED revisit, subsequent hospitalization, recurrent falls, and a composite outcome.

Results

There were 548 (86.3%) patients who completed follow‐up and 243 (44.3%) patients experienced an adverse event after a fall within 6 months. In multivariate analysis, seven questions from the STEADI guideline predicted various outcomes. The question “Had previous fall” predicted recurrent falls (odds ratio [OR] = 2.45, 95% confidence interval [CI] = 1.52 to 3.97), the question “Feels unsteady when walking sometimes” (OR = 2.34, 95% CI = 1.44 to 3.81), and “Lost some feeling in their feet” predicted recurrent falls. In addition to recurrent falls risk, the supplemental questions “Use or have been advised to use a cane or walker,” “Take medication that sometimes makes them feel light‐headed or more tired than usual,” “Take medication to help sleep or improve mood,” and “Have to rush to a toilet” predicted other outcomes.

Conclusion

A STEADI score of ≥4 did not predict adverse outcomes although seven individual questions from the STEADI guidelines were associated with increased adverse outcomes within 6 months. These may be organized into three categories (previous falls, physical activity, and high‐risk medications) and may assist emergency physicians to evaluate and refer high‐risk fall patients for a comprehensive falls evaluation.

     

Perceptions of the prevalence of cigarette smoking by peers: a study of Taiwanese, Filipino, and Thai high school students

Youth cigarette smoking is a major public health concern in Southeast Asia. A suspected determinant of youth smoking is perceived peer behavior. Previous research has suggested that the probability that a teenager will use substances increases when there is the perception that most peers engage in the substance use behavior. This study aimed to assess the perceptions of the prevalence of peer cigarette smoking in samples of high school students from three Southeast Asian countries and to examine the association of these perceptions to self-reported personal use of cigarettes. Perceptions of the prevalence of peer smoking were generally characterized by the perception that most students do not smoke. However, a significant percentage of students held the perception that most students were current smokers. Students who held this perception were at increased risk of being current smokers relative to those who believed most students were not current smokers. The results of this study imply that public health programs may benefit from health promotion interventions which focus on dispelling misconceptions that most youth smoke cigarettes.     

Evaluation of Plasmodium vivax isolates in Thailand using polymorphic markers Plasmodium merozoite surface protein (PvMSP) 1 and PvMSP3

Parasitology Research - Malaria is a significant public health problem in several tropical countries including Thailand. The prevalence of Plasmodium vivax infection has been increasing in the past...     

The validity of peer responses as a tool for screening at-risk students: a preliminary analysis

Students are becoming the majority of new amphetamine users in Thailand. This study compared urinalysis results with peer responses to individual characteristics related to substance use with the aim of identifying "at-risk" students. A randomly selected group of students from a public high school in northern Thailand was asked to fill out the names of classmates they viewed as having any of forty-three risk behaviors set out in a questionnaire. A total of 564 students were included, from whom urine specimens were collected on the first two days following the school break. An immunoassay test was used to screen the specimens and positive results were confirmed using thin-layer chromatography. About 4% of urinalysis results were methamphetamine-positive. Using urine test results as the standard, the sensitivity of peer responses to alienated behavior was 81.8%, while frequent class/school absenteeism and low concentration levels were somewhat lower, at 77% and 68%, respectively. Delinquency showed the least sensitivity at 50%. The McNemar chi2 test showed significant differences between urine test results and each peer response subscale (p < 0.001). This preliminary analysis has shown that peer responses with regard to substance-related behavior compare well with urine test results.     

Effects of hexahydrocurcumin in combination with 5-fluorouracil on dimethylhydrazine-induced colon cancer in rats

AIM: To investigate the effects of hexahydrocurcumin (HHC), and its combination with 5-fluorouracil (5-FU) on dimethylhydrazine (DMH)-induced colon cancer in rats.METHODS: Male Wistar rats weighing 100-120 g were used as subject models. Aberrant crypt foci (ACF), early preneoplastic lesions of colon cancer, were induced by subcutaneous injection of DHM (40 mg/kg) twice a week for two weeks. After the first DMH injection, rats were treated daily with vehicle (n = 12), curcumin (CUR) (50 mg/kg) (n = 12), HHC (50 mg/kg) orally (n = 12), and treated weekly with an intraperitoneal injection of 5-FU (50 mg/kg) (n = 12), or a combination of 5-FU plus CUR (n = 12) and HHC (n = 12) at the same dosage(s) for 16 wk. The total number of ACF and large ACF were assessed. Cyclooxygenase (COX)-1 and COX-2 expression were detected by immunohistochemistry in colon tissues. The quantitative data of both COX-1 and COX-2 expression were presented as the percentage of number of positive-stained cells to the total number of cells counted. Apoptotic cells in colon tissues were also visualized using the dUTP-biotin nick end labeling method. Apoptotic index (AI) was determined as the percentage of labeled nuclei with respect to the total number of nuclei counted.RESULTS: The total number of ACF was highest in the DMH-vehicle group (1558.20 ± 17.37), however, the number of ACF was significantly reduced by all treatments, 5-FU (1231.20 ± 25.62 vs 1558.20 ± 17.37, P < 0.001), CUR (1284.20 ± 25.47 vs 1558.20 ± 17.37, P < 0.001), HHC (1086.80 ± 53.47 vs 1558.20 ± 17.37, P < 0.001), DMH-5-FU + CUR (880.20 ± 13.67 vs 1558.20 ± 17.37, P < 0.001) and DMH-5-FU + HHC (665.80 ± 16.64 vs 1558.20 ± 17.37, P < 0.001). Interestingly, the total number of ACF in the combined treatment groups, the DMH-5-FU + CUR group (880.20 ± 13.67 vs 1231.20 ± 25.62, P < 0.001; 880.20 ± 13.67 vs 1284.20 ± 25.47, P < 0.001) and the DMH-5-FU + HHC group (665.80 ± 16.64 vs 1231.20 ± 25.62, P < 0.001; 665.80 ± 16.64 vs 1086.80 ± 53.47, P < 0.001) were significantly reduced as compared to 5-FU or each treatment alone. Large ACF were also significantly reduced in all treatment groups, 5-FU (111.00 ± 7.88 vs 262.20 ± 10.18, P < 0.001), CUR (178.00 ± 7.33 vs 262.20 ± 10.18, P < 0.001), HHC (186.60 ± 21.51 vs 262.20 ± 10.18, P < 0.001), DMH-5-FU + CUR (122.00 ± 5.94 vs 262.20 ± 10.18, P < 0.001) and DMH-5-FU + HHC (119.00 ± 17.92 vs 262.20 ± 10.18, P < 0.001) when compared to the vehicle group. Furthermore, in the DMH-5-FU + CUR and DMH-5-FU + HHC groups the formation of large ACF was significantly reduced when compared to CUR (122.00 ± 5.94 vs 178.00 ± 7.33, P < 0.005) or HHC treatment alone (119.00 ± 17.92 vs 186.60 ± 21.51, P < 0.001), however, this reduction was not statistically different to 5-FU monotherapy (122.00 ± 5.94 vs 111.00 ± 7.88, P = 0.217; 119.00 ± 17.92 vs 111.00 ± 7.88, P = 0.619, respectively). The levels of COX-1 protein after all treatments were not different from normal rats. A marked increase in the expression of COX-2 protein was observed in the DMH-vehicle group. Over-expression of COX-2 was not significantly decreased by 5-FU treatment alone (95.79 ± 1.60 vs 100 ± 0.00, P = 0.198). However, over-expression of COX-2 was significantly suppressed by CUR (77.52 ± 1.68 vs 100 ± 0.00, P < 0.001), HHC (71.33 ± 3.01 vs 100 ± 0.00, P < 0.001), 5-FU + CUR (76.25 ± 3.32 vs 100 ± 0.00, P < 0.001) and 5-FU + HHC (68.48 ± 2.24 vs 100 ± 0.00, P < 0.001) in the treated groups compared to the vehicle group. Moreover, CUR (77.52 ± 1.68 vs 95.79 ± 1.60, P < 0.001), HHC (71.33 ± 3.01 vs 95.79 ± 1.60, P < 0.001), 5-FU + CUR treatments (76.25 ± 3.32 vs 95.79 ± 1.60, P < 0.001) and 5-FU + HHC (68.48 ± 2.24 vs 95.79 ± 1.60, P < 0.001) markedly decreased COX-2 protein expression more than 5-FU alone. Furthermore, the AI in all treated groups, 5-FU (38.86 ± 4.73 vs 23.56 ± 2.12, P = 0.038), CUR (41.78 ± 6.92 vs 23.56 ± 2.12, P < 0.001), HHC (41.06 ± 4.81 vs 23.56 ± 2.12, P < 0.001), 5-FU + CUR (49.05 ± 6.75 vs 23.56 ± 2.12, P < 0.001) and 5-FU + HHC (53.69 ± 8.59 vs 23.56 ± 2.12, P < 0.001) significantly increased when compared to the DMH-vehicle group. However, the AI in the combination treatments, 5-FU + CUR (49.05 ± 6.75 vs 41.78 ± 6.92, P = 0.192; 49.05 ± 6.75 vs 38.86 ± 4.73, P = 0.771) and 5-FU + HHC (53.69 ± 8.59 vs 41.06 ± 4.81, P = 0.379; 53.69 ± 8.59 vs 38.86 ± 4.73, P = 0.245) did not reach significant levels as compared with each treatment alone and 5-FU monotherapy, respectively.CONCLUSION: The combined effects of HHC with 5-FU exhibit a synergistic inhibition by decreasing ACF formation mediated by down-regulation of COX-2 expression.     

Malignant craniopharyngioma; case report and review of the literature

A case of malignant craniopharyngioma in a 46‐year‐old woman presenting clinically with visual disturbance and bifrontal headache is reported. Histopathologic examination of the suprasellar mass showed a lesion characterized by nests of epithelial cells with a basaloid appearance, round‐to‐oval nuclei, moderate pleomorphism, hyperchromasia, increased nuclear cytoplastic ratio and high mitotic activity. Immunohistochemically, the tumor cells were positive for Ki‐67 (44.3%), p53 (98%), and p63 (100%), but negative for estrogen and progesterone receptors. Clinical and pathologic features with a brief review of the relevant literature for malignant craniopharyngioma as a novel member of tumors of the suprasellar region, is discussed.     

International reproducibility of single breathhold T2* MR for cardiac and liver iron assessment among five thalassemia centers

Purpose:

To examine the reproducibility of the single breathhold T2* technique from different scanners, after installation of standard methodology in five international centers.

Materials and Methods:

Up to 10 patients from each center were scanned twice locally for local interstudy reproducibility of heart and liver T2*, and then flown to a central MR facility to be rescanned on a reference scanner for intercenter reproducibility. Interobserver reproducibility for all scans was also assessed.

Results:

Of the 49 patients scanned, the intercenter reproducibility for T2* was 5.9% for the heart and 5.8% for the liver. Local interstudy reproducibility for T2* was 7.4% for the heart and 4.6% for the liver. Interobserver reproducibility for T2* was 5.4% for the heart and 4.4% for the liver.

Conclusion:

These data indicate that T2* MR may be developed into a widespread test for tissue siderosis providing that well‐defined and approved imaging and analysis techniques are used. J. Magn. Reson. Imaging 2010;32:315–319. © 2010 Wiley‐Liss, Inc.