Circadian rhythm sleep disorders as a possible side effect of fluvoxamine.

Sleep problems, day somnolence, and fatigue as a result of psychotropic drugs are very common. Psychiatrists usually consider these effects a result of insomnia and treat them by prescribing sleeping pills or other benzodiazepine agents. We describe here 10 cases of circadian rhythm sleep disorders (CRSD)--and not merely insomnia--as a possible side effect of fluvoxamine (FVA). Two other serotonin reuptake inhibitors, fluoxetine and clomipramine, did not induce CRSD in any of these 10 patients. We speculate that FVA-induced CRSD is caused by the effect of FVA on serotonin and melatonin levels in the central nervous system. CRSD as a side effect of FVA can be treated by replacing the suspected FVA or adding melatonin to a beneficial FVA treatment. Thus, it is important to be aware of possible iatrogenic CRSD in order to treat appropriately. Prospective studies are needed to confirm our observation and to study the influence of other psychotropic drugs on sleep-wake schedule.

Pupillography as an objective indicator of fatigue.

PURPOSE: To determine whether parameters calculated from pupillary activity can identify subjects with sleep deprivation, and whether the objective values correlate with a subjective feeling of fatigue. METHODS: pupil size in the dark was recorded continuously for 10 minutes in 12 healthy volunteers using an infrared video camera. Two recordings were made for each subject: after a full night's sleep, and after 24 hours of sleep deprivation. Several parameters calculated from pupil size and activity were analyzed and compared with a subjective rating of the state of alertness provided by the participants in each test. RESULTS: All pupillary parameters differed significantly between alertness and fatigue (p = 0.0076-0. 0186). Changes in one of the parameters - average pupillary diameter - correlated with changes in the subjective level of sleepiness (r = -0.51, p = 0.028). Although the values of most parameters differed among subjects, an absolute value of more than 25 in one parameter, cumulative pupillary variability ratio, was always associated with sleep deprivation. CONCLUSION: On-line analysis of the pupillogram using the suggested parameters can be performed easily to produce a real-time assessment of an individual's state of alertness or fatigue that correlates with his/her subjective assessment of this state.

Blood lactate recovery and perceived readiness to start a new run in middle-distance runners during interval training.

The aim of this study was to establish to what extent ratings of perceived readiness to start a new run are dependent on recovery of blood lactate and heart rate during passive recovery between interval runs (4 x 2000 m) of increasing intensity by 15 male college-level middle-distance runners. The Perceived Readiness Rating scale was administered at each minute of recovery. Blood lactate concentration was measured immediately after runs at Min. 3 of recovery after the first and second runs, and, in addition, at Min. 6 of recovery after the third and fourth runs. Heart rate was recorded continuously during the runs and during recovery. The obtained correlation between blood lactate recovery and perceived readiness ratings after the third and fourth runs were -.36 and -.56, respectively (p<.05). Consequently, blood lactate concentration recovery appears to influence the middle-distance runners' perceived readiness estimation to begin a new run. The Perceived Readiness Rating applied by us appears useful in the training of middle-distance runners.

Relationship between perceived readiness to run and physiological variables during repeated 2000 m bouts in middle-distance runners.

The aim of this study was to investigate how heart rate (HR) and blood lactate (LA) concentrations are associated with perceived readiness ratings (PRR) to begin a new run during recovery after four different intensity steady-state 2000 m runs in college-level male middle-distance runners (n=15). A typical 4x2000 m run test with stepwise increasing speed was used on the indoor track (150 m lap). A new PRR scale was administered at each minute of recovery. The scale ranges from 1 to 5 points (from "not at all ready to begin" to "completely ready to begin"). Blood LA concentrations were measured immediately after runs and in the 3rd min of recovery after the first and second runs. In case of the third and fourth runs, blood LA was measured immediately after the runs and in the 3rd and 6th min of recovery. HR was recorded at the end of every minute of recovery. Highly significant inverse relationships were revealed between PRR, blood LA concentrations and HR during recovery (r>0.9 as a rule). After the third and the fourth 2000 m runs, where intensity was higher than LA threshold, PRR increased during 6 min up to 4.8+/-0.4 and 4.5+/-0.6, respectively, while HR fell below 120 beats x min(-1). However, blood LA concentration remained high. The reliability of the new PRR scale (tested on four runners), during recovery was very high (r=0.98). These results suggest that the PRR scale can be used by runners to determine the optimal duration of resting intervals between runs.

Conditional transformation of a pancreatic beta-cell line derived from transgenic mice expressing a tetracycline-regulated oncogene.

Conditional oncogene expression in transgenic mice is of interest for studying the oncoprotein requirements during tumorigenesis and for deriving cell lines that can be induced to undergo growth arrest and enhance their differentiated functions. We utilized the bacterial tetracycline (Tet)-resistance operon regulatory system (tet) from Tn10 of Escherichia coli to control simian virus 40 (SV40) large tumor (T) antigen (TAg) gene expression and to generate conditionally transformed pancreatic beta cells in transgenic mice. A fusion protein containing the tet repressor (tetR) and the activating domain of the herpes simplex virus protein VP16, which converts the repressor into a transcription activator, was produced in beta cells of transgenic mice under control of the insulin promoter. In a separate lineage of transgenic mice, the TAg gene was introduced under control of a tandem array of tet operator sequences and a minimal promoter, which by itself is not sufficient for gene expression. Mice from the two lineages were then crossed to generate double-transgenic mice. Expression of the tetR fusion protein in beta cells activated TAg transcription, resulting in the development of beta-cell tumors. Tumors arising in the absence of Tet were cultured to derive a stable beta-cell line. Cell incubation in the presence of Tet led to inhibition of proliferation, as shown by decreased BrdUrd and [3H]thymidine incorporation. The Tet derivative anhydrotetracycline showed a 100-fold stronger inhibition compared with Tet. When administered in vivo, Tet efficiently inhibited beta-cell proliferation. These findings indicate that transformed beta cells selected for growth during a tumorigenesis process in vivo maintain a dependence on the continuous presence of the TAg oncoprotein for their proliferation. This system provides an approach for generation of beta-cell lines for cell therapy of diabetes as well as conditionally transformed cell lines from other cell types of interest.