Anti-tumor effect of bisphosphonate (YM529) on non-small cell lung cancer cell lines

BACKGROUND: YM529 is a newly developed nitrogen-containing bisphosphonate (BP) classified as a third-generation BP that shows a 100-fold greater potency against bone resorption than pamidronate, a second-generation BP. This agent is, therefore expected to be extremely useful clinically for the treatment of osteoporosis and hypercalcemia. Recently, YM529 as well as other third-generation BPs have also been shown to exert anti-tumor effects against various types of cancer cells both in vitro or/and in vivo. In this study, we investigate the anti-tumor effect of YM529 on non-small cell lung cancer (NSCLC). METHODS: Direct anti-tumor effect of YM529 against 8 NSCLC cell lines (adenocarcinoma: H23, H1299, NCI-H1819, NCI-H2009, H44, A549, adenosquamous cell carcinoma: NCI-H125, squamous cell carcinoma: NCI-H157) were measured by MTS assay and calculated inhibition concentration 50 % (IC(50)) values. YM529 induced apoptosis of NCI-H1819 was examined by DNA fragmentation of 2 % agarose gel electrophoresis and flowcytometric analysis (sub-G(1 )method). We examined where YM529 given effect to apoptosis of NSCLC cells in signaling pathway of the mevalonate pathway by western blotting analysis. RESULTS: We found that there was direct anti-tumor effect of YM529 on 8 NSCLC cell lines in a dose-dependent manner and their IC(50 )values were 2.1 to 7.9 μM and YM529 induced apoptosis and G(1 )arrest cell cycle with dose-dependent manner and YM529 caused down regulation of phospholyration of ERK1/2 in signaling pathways of NSCLC cell line (NCI-H1819). CONCLUSION: Our study demonstrate that YM529 showed direct anti-tumor effect on NSCLC cell lines in vitro, which supports the possibility that third-generation BPs including YM529 can be one of therapeutic options for NSCLC

Patients with erythrophobia (fear of blushing) show abnormal autonomic regulation in mental stress conditions

OBJECTIVE: The objective of this study was to analyze the autonomic functions of patients with erythrophobia. METHODS: Forty patients with a diagnosis of erythrophobia (female/male ratio 18/22) without any other organic lesions and 20 healthy volunteers (female/male ratio 10/10) were assessed. Clinical evaluation was performed using a modified version of semistructured interviews. Autonomic testing was performed by means of spectral analysis of heart rate and continuous blood pressure by sparse discrete Fourier transformation at rest and under mental stress. RESULTS: There were no significant difference between the two samples in age, sex distribution, BMI, resting systolic, or diastolic blood pressure, nor was there a difference in autonomic baseline functioning between the 40 patients with erythrophobia and the control subjects. On the other hand, patients with erythrophobia consistently showed higher pulse rates (88 +/- 20 vs. 78 +/- 9 bpm, p <.05), higher total heart rate power values (8.40 +/- 0.63 vs. 8.07 +/- 1.02 p <.05), higher midfrequency spectral values (7.38 +/- 0.66 vs. 7.02 +/- 1.18, p <.01), higher high-frequency spectral values (6.89 +/- 0.86 vs. 6.48 +/- 1.44, p <.05), and lower baroreceptor sensitivity (8.62 +/- 8.16 vs. 11.65 +/- 4.42, p <.005) than the healthy subjects. ANOVA showed a significant group interaction (p <.0001) between the samples. CONCLUSIONS: This study provides evidence for abnormal autonomic functioning in patients with erythrophobia when under mental stress

Khat chewing is a risk factor for acute myocardial infarction: a case-control study

Aim Khat chewing is a common habit in Yemen and east African countries. Millions of people chew khat leaves daily for its euphoric and energetic effects and to increase alertness. Cathinone, the main active substance in fresh khat leaves, has sympathomimetic effects which increase heart rate and blood pressure. The aim was to examine the hypothesis that khat chewing is a risk factor for acute myocardial infarction (AMI) using a hospital-based matched case-control study. Method Between 1997 and 1999, we selected 100 patients admitted to the Al-Thawra teaching hospital Sana’a ICU, Yemen with acute myocardial infarction. 100 control subjects, matched to cases for sex and age, were recruited from the outpatients clinics of the same hospital. A questionnaire was completed for case and control groups covering personal history of khat chewing, smoking, hypertension, diabetes and any family history of myocardial infarction. A blood sample was collected for performing lipid profiles. Cases and controls were compared by analysis conducted using conditional logistic regression which corrected for baseline imbalances leading to less biased estimations of odds ratio (OR). The risk associated with each classical factor and khat chewing habits was then investigated. OR values greater than 2.5 indicated a significant risk factor. Results Khat chewing was significantly higher among the AMI case group than control group (OR = 5.0, 95% CI 1.9–13.1). A dose–response relationship was observed, the heavy khat chewers having a 39-fold increased risk of AMI. Conclusion This study indicates that khat chewing is associated with AMI and is an independent dose-related risk factor for the development of myocardial infarction

Patterns or mechanisms? Bergmann’s and Rapoport’s rule in moths along an elevational gradient

Bergmann’s rule predicts increasing body sizes at higher elevations. The elevational Rapoport’s rule predicts an increase of elevational range size with higher elevations. Both rules have often been related to effects of temperature. Larger bodies allow more efficient heat preservation at lower temperature, explaining Bergmann’s rule. Higher temperature variability may select for adaptations that allow increased range sizes, explaining Rapoport’s rule. The generality of both rules has been challenged and evidence towards explanatory mechanisms has been equivocal. We investigated temperature and its variability as explanations for Bergmann’s and Rapoport’s rule in moths along an elevation gradient in Switzerland. In particular, we tested for relationships between elevation, temperature and body size across almost 300 species of Macrolepidoptera along a gradient from 600 to 2400 m a.s.l. The gradient was resampled throughout the vegetation season, which allowed assessing temperature effects independently from elevation. We controlled analyses for covariate traits of moths and their phylogeny. We found a positive relationship between body size and elevation, but no link with temperature. Furthermore, there was no positive link between average elevation and elevational range, but there was between temperature variability and elevational range. We conclude that mechanisms other than temperature can lead to increasing body sizes with elevation (supporting Bergmann’s pattern, but not the mechanism). Contrary to that, data support the mechanism for Rapoport’s rule: high temperature variability is associated with large ranges. However, because temperature variability is not necessarily increasing with elevation, it may not always lead to the geographic pattern predicted

Patterns or mechanisms? Bergmann's and Rapoport's rule in moths along an elevational gradient

Bergmann's rule predicts increasing body sizes at higher elevations. The elevational Rapoport's rule predicts an increase of elevational range size with higher elevations. Both rules have often been related to effects of temperature. Larger bodies allow more efficient heat preservation at lower temperature, explaining Bergmann's rule. Higher temperature variability may select for adaptations that allow increased range sizes, explaining Rapoport's rule. The generality of both rules has been challenged and evidence towards explanatory mechanisms has been equivocal. We investigated temperature and its variability as explanations for Bergmann's and Rapoport's rule in moths along an elevation gradient in Switzerland. In particular, we tested for relationships between elevation, temperature and body size across almost 300 species of Macrolepidoptera along a gradient from 600 to 2400 m a.s.l. The gradient was resampled throughout the vegetation season, which allowed assessing temperature effects independently from elevation. We controlled analyses for covariate traits of moths and their phylogeny. We found a positive relationship between body size and elevation, but no link with temperature. Furthermore, there was no positive link between average elevation and elevational range, but there was between temperature variability and elevational range. We conclude that mechanisms other than temperature can lead to increasing body sizes with elevation (supporting Bergmann's pattern, but not the mechanism). Contrary to that, data support the mechanism for Rapoport's rule: high temperature variability is associated with large ranges. However, because temperature variability is not necessarily increasing with elevation, it may not always lead to the geographic pattern predicted