Studying the snail's clock at better than a snail's pace.

The eye of Bulla gouldiana, the cloudy bubble snail, contains a circadian pacemaker that times a nocturnal locomotor rhythm. The eye expresses a circadian rhythm in spontaneous impulse activity that is generated within individual neurons at the base of the retina. There are approximately 100 of these "clock neurons" that are electrically interconnected. The retinal clock can be synchronized by light cycles. Synchronization involves membrane depolarization and calcium influx into pacemaker neurons. While rhythm expression involves an ionic calcium flux, and rhythm expression appears to be mediated by changes in potassium conductance, circadian rhythm generation does not appear to rely on transmembrane fluxes. Rather, the molecular events of transcription and translation appear to be critical players in generating the near twenty-four-hour rhythm in optic nerve activity.

Studying the snail's clock at better than a snail's pace

The eye of Bulla gouldiana, the cloudy bubble snail, contains a circadian pacemaker that times a nocturnal locomotor rhythm. The eye expresses a circadian rhythm in spontaneous impulse activity that is generated within individual neurons at the base of the retina. There are approximately 100 of these "clock neurons" that are electrically interconnected. The retinal clock can be synchronized by light cycles. Synchronization involves membrane depolarization and calcium influx into pacemaker neurons. While rhythm expression involves an ionic calcium flux, and rhythm expression appears to be mediated by changes in potassium conductance, circadian rhythm generation does not appear to rely on transmembrane fluxes. Rather, the molecular events of transcription and translation appear to be critical players in generating the near twenty-four-hour rhythm in optic nerve activity.

Association of acetaminophen hepatotoxicity with fasting and ethanol use.

OBJECTIVES: To evaluate the association of fasting and alcohol use with hepatotoxicity from acetaminophen ingested for therapeutic reasons. DESIGN: Retrospective case series. SETTING: Hospitals of the University of Pittsburgh (Pa) Medical Center. PATIENTS: A total of 126,779 discharge summaries from January 1987 to July 1993 were reviewed using a comprehensive, whole-text-indexed medical database to identify all patients with acetaminophen ingestion and hepatotoxicity. These patients were categorized according to the intended acetaminophen use and dose of acetaminophen ingested. MAIN OUTCOMES MEASURED: The independent variables of chronic alcohol use, recent alcohol use, and recent fasting were determined for all patients. RESULTS: Forty-nine patients with acetaminophen hepatotoxicity (aspartate aminotransferase > 1000 U/L) were identified. Twenty-one patients (43%) ingested acetaminophen for therapeutic purposes. All patients with hepatotoxicity took more than the recommended limit of 4 g/d. Recent fasting was more common than recent alcohol use among those who suffered hepatotoxicity after a dose of 4 to 10 g of acetaminophen per day (P = .02). Recent alcohol use was more common in the group who took more than 10 g/d than in those who took 4 to 10 g/d (P = .004). CONCLUSION: Acetaminophen hepatotoxicity after a dose of 4 to 10 g/d was associated with fasting and less commonly with alcohol use. Patients who developed hepatoxicity after taking acetaminophen doses of greater than 10 g/d for therapeutic purposes were alcohol users. Acetaminophen hepatotoxicity after an overdose appears to be enhanced by fasting in addition to alcohol ingestion.

Protocerebral circadian pacemakers in crayfish: evidence for mutually coupled pacemakers.

Similar to intact crayfish, animals with an isolated protocerebrum-eyestalk complex, exhibit competent circadian rhythms in the electroretinogram (ERG). The ERG rhythms of the two eyes remain in phase after isolation of the protocerebrum but can be desynchronized after surgical bisection of the protocerebrum. The desynchrony of the two ERG rhythms reveals the existence of at least two circadian pacemakers in the eyestalk-protocerebrum complex. In addition, the fact that desynchrony of the ERG rhythms only occurs in bisected preparations suggests that pathways between the protocerebral lobes normally couple the two pacemakers.