Effect of flurbiprofen, metoclopramide and droperidol for nausea and emesis during cesarean section under spinal anesthesia.

PURPOSE: Nausea and emesis frequently arise during cesarean section performed under spinal or epidural anesthesia, particularly after delivery. We have evaluated the treatment effects of flurbiprofen, metoclopramide and droperidol on nausea and emesis during cesarean section in patients under combined spinal and epidural anesthesia. METHODS: The patient cohort comprised 361 patients with American Society of Anesthesiologists (ASA) physical status I or II who elected to undergo cesarean section. All patients received combined spinal-epidural anesthesia. After delivery, nausea and emesis was assessed using a 4-point scale as: 1, excellent, with no complaints; 2, mild nausea; 3, severe nausea; 4, emesis. Patients who experienced severe nausea or emesis were randomly assigned to receive one of the following intravenous drugs: Group A, flurbiprofen (50 mg); Group B, metoclopramide (10 mg); Group C, droperidol (1.25 mg). Effects on nausea and emesis were assessed at 5, 10 and 15 min after drug administration using a 4-point scale as: 1, obviously improved; 2, improved; 3, unchanged; 4 worsened. RESULTS: Among the patients, 151 reported nausea or emesis. These patients experienced a longer duration of surgery and anesthesia and lost more blood than patients with no complaints. The frequency of improvement in the flurbiprofen group was significantly higher than that in the metoclopramide group at 5, 10 and 15 min (p < 0.05) after administration, and of that in the droperidol group at 15 min after administration (p < 0.05). CONCLUSION: Intravenous flurbiprofen improves nausea and emesis after delivery by cesarean section more effectively than metoclopramide or droperidol.

External Ca2+ dependency of synaptic transmission in drosophila synaptotagmin I mutants.

To resolve some of differences in reports on the function of Synaptotagmin I (Syt I), we re-examined synaptic transmission at the neuromuscular junction of Drosophila embryos that have mutations in the Syt I gene (syt I). Two major questions addressed were which Ca2+ binding domain, C2A or C2B, sense Ca2+ and is Syt I a negative regulator of spontaneous vesicle fusion. Synaptic currents were induced by nerve stimulation or by high K+ treatment in external solutions containing various Ca2+ concentrations. In a null allele, syt I(AD4), synchronous synaptic currents were rarely observed but not abolished. The quantal content was about 1/60 of control but increased linearly with [Ca2+](e) with a slope of 0.95 (N) in the double logarithmic plot, in contrast to 3.01 in control. The slope of 1.06 in an allele, syt I(AD1), which lacks the second Ca2+ binding domain, C2B, was not different from in syt I(AD4). In another allele, syt I(AD3), in which one amino acid in C2B is mutated, synchronous synaptic transmission was also impaired and N was 1.54, which is significantly smaller than in control. In high K+ saline, the [Ca2+](e) dependency of vesicle release in syt I(AD4) was lower than in controls, whereas that in syt I(AD3) was even lower than in syt I(AD4), suggesting that syt I(AD3) is inhibiting vesicle fusion. These findings led us to conclude that C2B, not C2A, senses Ca2+, and Syt I is a negative regulator of vesicle fusion.

[Molecular mechanism of morphine tolerance and biological approaches to resolve tolerance].

One of the major problems associated with the chronic use of morphine is tolerance. Repeated uses of morphine to relieve pain often cause patients to develop increasing resistance to the effects of the drugs, so that progressively higher doses are required to achieve the same analgesic effects. Acquired tolerance is thought to be different from dependence or addiction, but molecular mechanism underlying the development of tolerance is still unclear. Tolerance has been explained by desensitization of opioid receptor signaling and loss of functional receptors in the cell surface. The classical hypothesis was that phosphorylation and arrestin binding resulted in uncoupling of the receptor from G proteins, and reduced agonist efficacy. The receptor internalization would then result in fewer functional receptors at the cell surface. These events would cause so-called signaling desensitization. However, recent molecular biological studies have led researchers to revise the classical view of tolerance from observations that morphine does not always promote efficient receptor internalization. Among several key processes, the sequestration and subsequent internalization of the opioid receptor may play an important role for morphine tolerance. In fact, recent studies have suggested that receptor internalization can reduce tolerance. In addition, activation of the NMDA subtype of the glutamate receptor has been suggested as an anti-opioid system in the development of morphine tolerance. In this review, we focus on recent research progress on the morphine tolerance, and molecular biological and clinical approaches to resolve morphine tolerance.

Intracellular calcium increases in growth cones exposed to tetracaine.

UNLABELLED: Neurotoxicity of local anesthetics has been reported for both matured and growing neurons. In the present study, we examined if tetracaine increases Ca(2+) concentration during growth cone collapse. Intracellular Ca(2+) concentration was measured by fura 2/AM after exposure to tetracaine. Tetracaine (1-2 mM) induced increases in intra-growth cone Ca(2+) concentration (P < 0.01). The Ca(2+) hot spot was expanded into the neurite from the periphery towards the cell body. When tetracaine was applied to growth cones in Ca(2+) free media, the increase was minor. However, tetracaine induced growth cone collapse even in the culture media, which did not contain Ca(2+). Ni(2+) (100 microM; a general Ca(2+) channel inhibitor) and BAPTA-AM (5 microM; intracellular Ca(2+) chelator) could not inhibit growth cone collapse induced by 1-2 mM tetracaine. Tetracaine (>1 mM) induces collapse and Ca(2+) increase at growth cones simultaneously; however, these two phenomena might be provoked independently. IMPLICATIONS: Tetracaine induced intracellular Ca(2+) increases and growth cone collapse in dorsal root ganglion neurons. The Ca(2+) hot spot in the growth cone expanded into the neurite from periphery towards the cell body.

[Blood-brain barrier and general anesthetics].

The transport of drugs into the brain is prevented in most cases by the presence of the blood brain barrier (BBB). Endothelial cells in the brain of vertebrates are fused together by tight junctions that eliminate the normal pathways of free diffusion existing in the capillary beds of organs other than the brain or spinal cord. Therefore, a molecule that has a molecular weight less than a 500 Dalton can cross the BBB in proportion to lipid solubility. Recent molecular biological studies have contributed to the isolation and functional analysis of transporter proteins at the BBB. There are three types of endogenous transport systems: carrier-mediated transporters, active efflux transporters such as P-glycoprotein, and receptor-mediated transcytosis systems. The structural and functional integrity of the BBB has appeared to be dramatically altered by various diseases of the CNS such as ischemia, anoxia and inflammation, resulting in cerebral edema and damage to the neurons. General anesthetic agents can alter the BBB function. For example, the degree of the BBB disruption was smaller during isoflurane anesthesia than during pentobarbital anesthesia. In this review, we focus on recent progress in the BBB research and functional modulation produced by general anesthetics.

Biphasic modulation of synaptic transmission by hypertonicity at the embryonic Drosophila neuromuscular junction.

Puff-application of hypertonic saline (sucrose added to external saline) causes a transient increase in the frequency of spontaneous miniature synaptic currents (mSCs) at the neuromuscular junctions of Drosophila embryos. The frequency gradually returns to pre-application levels. External Ca(2+) is not needed for this response, but it may modify it. At 50 mM added sucrose, for example, enhanced spontaneous release was observed only in the presence of external Ca(2+), suggesting that Ca(2+) augments the response. In a high-K(+) solution, in which the basal mSC frequency was elevated, higher sucrose concentrations produced an increase in mSC frequency that was followed (during and after the hypertonic exposure) by depression, with the magnitude of both effects increasing with hypertonicity between 100 and 500 mM. Evoked release by nerve stimulation showed only depression in response to hypertonicity. We do not believe that the depression of spontaneous or evoked release can be explained by the depletion of releasable quanta, however, since the frequency of quantal release did not reach levels compatible with this explanation and the enhancement and depression could be obtained independent of one another. In a mutant lacking neuronal synaptobrevin, only the depression of mSC frequency was induced by hypertonicity. Conversely, only the enhancing effect was observed in wild-type embryos when the mSC frequency was elevated with forskolin in Ca(2+)-free saline. In cultured embryonic Drosophila neurons, Ca(2+) signals that were induced by high K(+) and detected by Fura-2, were reduced by hypertonicity, suggesting that the depressing response is due to a direct effect of hypertonicity on Ca(2+) influx.

Increasing ploidy level in cell suspension cultures of Doritaenopsis by exogenous application of 2,4-dichlorophenoxyacetic acid.

To clarify the causal factors for ploidy variation in plant cell culture, we attempted to alter ploidy distribution in cell cultures of a tetraploid cultivar of Doritaenopsis by changing the plant growth regulators (PGRs) in the culture medium. The original suspension cultured cells, which had been maintained in medium containing 0.1 mg l-1 1-naphthaleneacetic acid and 1 mg l-1 benzyladenine, were transferred onto various gellan gum solidified media with a single application of PGRs, and the ploidy distributions of the cells were examined using flow cytometry analysis during 3 weeks of culture. Among the PGRs tested, 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-amino-3,5,6-trichloropicolinic acid caused a drastic reduction in the 4C-cell proportion in cell cultures with an increased cell proportion of 8C or higher C-values. In the case of 2,4-D application, a reduction of cell viability was observed. A decreasing proportion was also observed in the 8C-cell population accumulated by 2,4-D treatment, following transfer back to the medium containing the standard PGR composition. These results suggest that the exogenous application of 2,4-D arrested the cell cycle at G2 phase in the Doritaenopsis cells, and the removal of 2,4-D might induce further endoreduplication or recover the mitotic cycle of the G2-arrested cells.