Caffeine does not cause override of the G2/M block induced by UVc or gamma radiation in normal human skin fibroblasts

Caffeine has for many years been known to be involved in the sensitization of DNA to damage. One potential mechanism recently put forward is an override of the G2/M block induced by irradiation, which would leave the cells less time for DNA repair prior to mitosis. However, different cell types display a variety of responses and no clear pathway has yet emerged, especially as little is known about the capacity of this agent to enhance DNA damage in normal, untransformed cells. Continuous exposure to commonly used caffeine concentrations (1-5 mM) inhibited the proliferation of normal human fibroblasts (NHFs) in a dose-dependent manner to up to 80% at 5 mM. Exposure of exponentially growing NHFs to UVc radiation (20 J m(-2)) or gamma radiation (2.5-8 Gy) led to a 45-60% inhibition of proliferation and protracted accumulation of cells in the G2/M phase. Addition of 2 mM caffeine after irradiation induced slowing of the S phase passage, with a resultant delay in G2/M accumulation mimicking a G2/M block override. These results were confirmed by stathmokinetic studies, which showed delayed entry of the cells into mitosis in the presence of caffeine. Our data demonstrate that caffeine primarily inhibits replicative DNA synthesis and suggest that, at least in normal cells, caffeine potentiates the cytotoxicity of radiation by intervening in DNA repair rather than by overriding the G2/M block.     

小波变换-比值导数光谱法同时测定脑清片中氨基比林和咖啡因的含量

目的　建立小波变换-比值导数光谱法（WT-RDS）,考察其在多组分样品含量测定中去除高频噪音干扰的作用。方法　采用WT-RDS同时测定脑清片中氨基比林和咖啡因的含量,以两组分样品的原始光谱除以其中某一组分的标准光谱后得到比值光谱,再以比值光谱对波长求导得到比值导数光谱。选取适当波长的振幅值测定,可消除一个组分的干扰而测定另一组分的含量;比较各实验数据小波变换前后处理的结果。结果　采用小波变换技术可消除测定组分的比值导数光谱中被“放大”的噪音的影响,实验数据的线性关系、精密度等得到改善。结论　WT-RDS灵敏度高,抗干扰能力强,结果可靠。     

Simultaneous analysis of sister chromatid exchanges and cell cycle delay

Institute of Medical Genetics, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR N. P. Bochkov). Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 105, No. 5, pp. 589–591, May, 1988.     

A New Optical Technique for Evaluating Collective Motility of Ram and Bull Ejaculated Spermatozoa

A new. non-destructive, objective technique for measuring collective motility of highly-concentrated ram and bull semen is described. The principle is based on changes in the reflected light scattered by motile spermatozoa. These changes can be recorded as a continuous analog wave pattern (Reflectospermiogram-RSG) and are correlated to the intensity of the turbulent motility as evaluated subjectively with an ordinary light microscope. Ram spermatozoa have, after ejaculation, a typical motility pattern, i.e., high, stable activity for about 20 min, then a period during which the motility decreases at a constant rate, and finally, a period with a low but rather constant activity. The usefulness of the technique has been demonstrated in various types of experiments.     

The effect of fluid intake on urinary symptoms in women

PURPOSE: We determined the effect of caffeine restriction and fluid manipulation in the treatment of patients with urodynamic stress incontinence and detrusor overactivity. MATERIALS AND METHODS: This was a 4-week randomized, prospective, observational crossover study in 110 women with urodynamic stress incontinence (USI) or idiopathic detrusor overactivity (IDO) to determine the effect of caffeine restriction, and of increasing and decreasing fluid intake on urinary symptoms. Data were recorded in a urinary diary for the entire study period on urgency episodes, frequency, pad weight increase, wetting episodes and quality of life. RESULTS: A total of 69 women with a mean age of 54.8 years completed the study, including 39 with USI and 30 with IDO. In the IDO group decreasing fluid intake significantly decreased voiding frequency, urgency and wetting episodes with improved quality of life. In the USI group there was a significant decrease in wetting episodes when fluid intake was decreased. Changing from caffeine containing to decaffeinated drinks produced no improvement in symptoms. CONCLUSIONS: Conservative and life-style interventions are first line treatments in the management of incontinence and storage lower urinary tract symptoms. This study shows that a decrease in fluid intake improves some of these symptoms in patients with USI and IDO and, therefore, it should be considered when treating such patients.     

Effects of caffeine on human aggressive behavior

A new methodology was employed to study the effects of caffeine on human aggressive behavior in a laboratory situation. Aggressive responding was elicited by subtracting money from the research subjects, which was attributed to a fictitious person. Caffeine compared to placebo produced decreases in two types of aggressive responses, but increased nonaggressive monetary reinforced responding. Thus, the suppressing effect of caffeine on aggressive responding was not due to a nonspecific depressant action.     

Effects of caffeine on linear and nonlinear measures of heart rate variability before and after exercise

Caffeine intake is associated with an increase in heart rate (HR) variability. This study sought to examine the effects of caffeine on HR variability measures before and during progressive exercise in 11 healthy volunteers in a double-blind randomized and counterbalanced placebo-controlled paradigm. As expected, there were significant increases in HR and decreases in HR variability after exercise during both placebo and caffeine conditions; however, pre-exercise caffeine condition was associated with a significant increase of HR variability, especially in the high-frequency range (0.15-0.5 Hz), and also approximate entropy (APEN), which is usually attributed to cardiac vagal function. But during progressive exercise, caffeine intake resulted in a greater decrease of HF power as well as HR APEN. Caffeine also was associated with significantly higher LF power during exercise compared to the placebo condition. These results suggest that caffeine may have different effects on HR variability at rest, compared to exercise. These findings may have implications for patients with cardiac illness and anxiety, depression, and psychotic disorders who use beverages containing excessive caffeine.     

The appetite-suppressant effect of nicotine is enhanced by caffeine

AIM: To test whether the anorectic effect of nicotine may be amplified by caffeine. METHODS: Chewing gums with nicotine and caffeine were administered to 12 healthy young men of normal weight. Different combinations of 0, 1 or 2 mg of nicotine and 0, 50 or 100 mg of caffeine were applied during a 2-h period in a randomized, double blind, cross over design. Appetite sensations were measured using visual analogue scales. RESULTS: Hunger and prospective food consumption were negatively associated with the increasing doses of nicotine, whereas satiety and fullness were positively associated with the increasing doses of nicotine (p < 0.05). Caffeine appeared to amplify the effects of nicotine on hunger and fullness as a caffeine x nicotine x time interaction was observed in these scores (p < 0.05). The 2-mg dose of nicotine in combination with the 100-mg dose of caffeine caused nausea in four of the non-smokers. However, the effects of nicotine and the caffeine x nicotine x time interaction persisted after the exclusion of these subjects. CONCLUSION: Caffeine added to nicotine chewing gum appears to amplify its attenuating effects on appetite and the combinations of 1-mg of nicotine with caffeine seem to be well tolerated.     

Rapid determination method of caffeine and application to monitoring of caffeine-assisted chemotherapy

Caffeine-assisted chemotherapy for bone and soft tissue tumours is very effective. However, high serum caffeine concentrations cause severe side effects, so monitoring of the serum level during therapy is important. For this purpose, a rapid determination method was established by high-performance liquid chromatography after solid-phase extraction. This method can measure caffeine and its three major metabolites in serum samples within 8 min. The mean serum caffeine concentrations of patients were 34.6+/-7.8, 54.5+/-11.9 and 73.0+/-12.8 microg/ml at 24, 48 and 72 h, respectively, after the start of a 1500 mg/m2/day continuous infusion for 72 h. The distribution volume of caffeine was 0.65+/-0.23 l/kg, and the total body clearance was 0.025+/-0.011 l/h/kg, which was one-third of the reported low dose clearance. The appropriate infusion rate was calculated to avoid severe side effects in the final phase of the infusion by using a one-compartment constant infusion model based on the serum levels measured at 24 and 48 h. Caffeine clearance did not correlate with the metabolite/caffeine ratio in serum at any time. It is concluded that individual monitoring with this method for the purpose of dose adjustment is useful for avoiding the side effects of caffeine-assisted chemotherapy.