Enzymuria in carboplatin nephrotoxicity

Urinary excretion of N-acetyl-beta-glucosaminidase (NAG) is an early marker of nephrotoxicity. NAG activity was assayed by the fluorimetric method of Leaback and Walker in 17 patients treated (22 courses) with carboplatin (CBDCA, 220-550 mg/m2) before infusion and 24, 48, 72 and 96 h after. Increased excretion of NAG, a sensitive index of renal tubular damage, was observed following 10 of the 22 courses. A transient increase in plasma creatinine and/or abnormal proteinuria was observed in 6 cases. Impaired renal function prior to therapy seems to be a predisposing factor to the nephrotoxicity.     

Intracerebroventricular injection of hemicholinium-3 prevents the ACTH-induced, but not the physostigmine-induced, reversal of hemorrhagic shock in rats

In rats bled to hypovolemic shock, the intracerebroventricular injection of hemicholinium-3 (20 micrograms/rat) completely prevented the shock reversal induced by the intravenous injection of ACTH (1-24) (160 micrograms/kg), but had no influence on the shock reversal induced by the intravenous injection of physostigmine (70 micrograms/kg). These data indicate that brain cholinergic neurons are involved in the anti-shock effect of ACTH-peptides, but not in that of centrally acting cholinergic drugs.     

Influence of ovariectomy, estradiol and progesterone on the behavior of mice in an experimental model of depression

In the tail suspension test (an animal model of depression) the duration of immobility during the 6 min of observation was 56.84 +/- 6.54 sec in sham-ovariectomized mice and 113.11 +/- 7.86 sec 30-32 days after ovariectomy. Estradiol (10, 100 or 1,000 micrograms/kg) and progesterone (50, 1,000 or 10,000 micrograms/kg), subcutaneously injected daily 4 times before the test, restored the duration of immobility in ovariectomized mice to normal, while having no effect on sham-operated animals. On the other hand, desipramine (20 mg/kg IP 1 hr before testing) significantly reduced the duration of immobility both in ovariectomized and in sham-operated mice. These data indicate that ovarian sex hormones, while having no "antidepressant," desipramine-like, effect on the behavior of intact adult female mice, have such an effect in ovariectomized mice, and enable the animal to cope in a "normal" way with adverse environmental situations.     

Chronic administration ofl-sulpiride at non-neuroleptic doses reduces the duration of immobility in experimental models of “depression-like” behavior

It has been shown that long-term administration ofl-sulpiride induces a down-regulation of receptor-associated adenylate cyclase activity in the frontal cortex of rats, an adaptive response that is typically associated with the chronic administration of antidepressants. Here we show that in two animal models of depression-like behavior (forced swim in rats and tail suspension in mice), the long-term (21 days) administration ofl-sulpiride at a non-neuroleptic dose (2 mg/kg IP twice a day) significantly decreases the duration of immobility, the effect being similar to that of desipramine (20 mg/kg IP). The same dose (2 mg/kg) ofl-sulpiride, acutely administered, has no effect at all. On the other hand, either chronic (21 days) or acute administration of neuroleptic doses ofl-sulpiride have an opposite effect, and indeed increase the duration of immobility. These results are an in vivo support to the in vitro findings suggesting that low doses ofl-sulpiride may have antidepressant-like activity.     

Calculated and measured oxygen consumption in mechanically ventilated surgical patients in the early post-operative period

Oxygen consumption (VO2) measured by indirect calorimetry (Nellcor-Puritan-Bennett 7250; Carlsbad, CA, USA) has been compared with VO2 calculated by the Fick method in 22 volume-controlled ventilated general surgical patients in the early post-operative period. For 198 pairs of measurements, VO2 Fick and VO2 indirect calorimetry correlated significantly (y = 1.00x - 35.8, P = 0.0001, r = 0.77). VO2 indirect calorimetry was 212 +/- 32 mL min-1 and VO2 Fick was 177 +/- 41 mL min-1 (P = 0.0001). The bias was 35 +/- 26 mL min-1. This difference represents 16 +/- 13% of the total body VO2. VO2 calculated by the Fick method did not accurately predict VO2 measured by indirect calorimetry, and the two methods were not interchangeable. VO2 calculated by the Fick method underestimated VO2 as measured by indirect calorimetry by a systematic quantity that could be attributed, in part, to VO2 of the lung. Indirect calorimetry should be the preferred method for measuring total body VO2 in mechanically ventilated surgical patients.     

l-Sulpiride, at a low, non-neuroleptic dose, prevents conditioned fear stress-induced freezing behavior in rats

Antidepressant drugs are effective in anxiety states, including panic disorder. Both clinical and animal studies indicate that l-sulpiride, at low, non-neuroleptic doses, has antidepressant activity. The present study examined the effect of an antidepressant dose of l-sulpiride (4 mg/kg per day SC), compared with a well-established antidepressant drug (fluoxetine, 3 mg/ kg per day SC), in a rat model of anticipatory anxiety/panic behavior: conditioned fear stress-induced freezing behavior. Long-term (26 days) administration of l-sulpiride almost completely abolished freezing, a similar effect being produced by fluoxetine (freezing duration, in seconds: controls, 148.1 ± 29.6; l-sulpiride, 27.5 ± 8.3; fluoxetine, 72.0 ± 15.2). The same doses of l-sulpiride (4 mg/kg SC) and fluoxetine (3 mg/kg SC) had no effect when administered for shorter periods (1, 5, or 12 days). No effect was produced by the long-term (26 days) administration of a neuroleptic dose of l-sulpiride (20 mg/kg per day SC). These results demonstrate that long-term administration of low, non-neuroleptic doses of l-sulpiride, is highly effective in an animal model of anticipatory anxiety/panic behavior. Received: 13 March 1998/Final version: 23 July 1998