Effect and safety of paroxetine combined with zolpidem in treatment of primary insomnia.

PURPOSE: Primary insomnia is a persistent and recurrent disorder as well as a risk factor for depression. The aim of this study was to determine whether the zolpidem combined with paroxetine would be effective in the treatment of patients with primary insomnia. METHODS: Ninety patients meeting DSM-IV criteria for primary insomnia were randomly assigned to 8 weeks of treatment with zolpidem combined with paroxetine (the combined treatment group, n = 45) or zolpidem combined with placebo (the control group, n = 45). Patients were assessed with the Pittsburgh Sleep Quality Index (PSQI), polysomnography (PSG), and the Treatment Emergent Symptom Scale (TESS). RESULTS: Compared with the control group, the combined treatment group was more significantly improved on wake time after sleep onset (WASO), total sleep time (TST), sleep efficiency (SE), and total PSQI scores, but not the sleep onset latency (SOL). CONCLUSIONS: Eight weeks of the zolpidem combined with paroxetine treatment to patients with primary insomnia is more effective than zolpidem treatment only in sleep maintenance and early morning awakenings.

Minimum local analgesic concentration of ropivacaine for intra-operative caudal analgesia in pre-school and school age children.

We compared the minimum local analgesia concentration of ropivacaine for intra-operative caudal analgesia in pre-school and school age children. Fifty-one boys, undergoing hypospadius repair surgery, were stratified into pre-school or school age groups. After induction of anaesthesia, caudal block was performed with ropivacaine 1 ml.kg⁻¹ of the desired concentration. The first child in each group received ropivacaine 0.125%, and subsequent concentrations were determined by the analgesic response of the previous patient using Dixon's up-and-down method. Under general anaesthesia with 0.7 minimum alveolar concentration of sevoflurane, the minimum local analgesia concentration of ropivacaine for intra-operative caudal block was 34% greater in school age than in pre-school age boys (0.143% (95% CI 0.132-0.157%) vs 0.107% (95% CI 0.089-0.122%), respectively; p < 0.001). This study indicates that a higher concentration of ropivacaine is needed for school age than pre-school age children to provide intra-operative caudal analgesia when combined with general anaesthesia.

The use of midazolam and small-dose ketamine for sedation and analgesia during local anesthesia.

UNLABELLED: Small-dose ketamine in combination with sedative drugs has increasingly been used for sedation and analgesia in local anesthesia. We compared the clinical efficacy of midazolam with two different ketamine infusion regimens during plastic surgery under local anesthesia. Sixty patients undergoing plastic surgery procedures with local anesthesia were randomly assigned to two groups of 30 patients each in a double-blinded fashion. All patients received a bolus of 0.05 mg/kg midazolam, followed by a stepwise infusion: 1.67 microg x kg(-1) x min(-1) for the first 30 min, then reduced to 1.33 microg x kg(-1) x min(-1) for 90 min and subsequently to 1 microg x kg(-1) x min(-1). Two minutes before the infiltration of local anesthetic solution, a bolus of ketamine 0.3 mg/kg IV was administered, followed by a stepwise infusion of ketamine: Group A, 16.67 microg x kg(-1) x min(-1) for 30 min, 13.3 microg x kg(-1) x min(-1) for 90 min, and subsequently 10 microg x kg(-1) x min(-1); Group B, 8.33 microg x kg(-1) x min(-1) for 30 min, 6.67 microg x kg(-1) x min(-1) for 90 min, and then 5 microg x kg(-1) x min(-1). The level of sedation was evaluated by using the modified Observer's Assessment of Alertness/Sedation scale. We observed the effects of the two ketamine infusion regimens on sedation levels, respiratory and cardiovascular variables, and perioperative side effects. In both groups, midazolam and ketamine produced adequate sedation (with Observer's Assessment of Alertness/Sedation scores of 2-4) without significant respiratory and cardiovascular depression during surgery. However, there were fewer disruptive movements and there was less postoperative vomiting in Group B (P < 0.01). In conclusion, ketamine and midazolam provided satisfactory intraoperative sedation, analgesia, and amnesia in both groups. However, side effects associated with ketamine occurred less often in the smaller-dose ketamine group. IMPLICATIONS: Sedation and analgesia are often provided during local anesthesia. This study demonstrates that a small-dose ketamine infusion in combination with midazolam provided satisfactory intraoperative sedation, analgesia, and amnesia in healthy plastic-surgery patients when it was used to supplement local anesthesia.

[Glutamate causes release of nitric oxide from chicken spinal cord in vitro].

Nitric oxide (NO) has been identified to have profound effects on many systems, especially the neural tissues. Many studies suggest that NO mediate the neurotoxicity of glutamate (Glu). In order to determine in vitro whether Glu causes release of NO from chicken spinal cord, different concentrations of Glu (0.1, 0.5, 1.0 mmol.L-1) were added to the primary cultured chicken spinal cord cells, and the quantity of NO- (the metabolism product of NO) in medium was detected. The result shows that Glu can enhance obviously the concentration of NO in primary cell cultures (212% compared with the control). If the spinal cord cells were pretreated with NO synthases (NOS) inhibitor--L-NOARG, the [NO-] was decreased compared with those treated with Glu only, and, on the contrary, the viability of cells was increased. All of the results above indicate that NO may play an important role in the neurotoxicity of Glu on nervous cells. It might be that Glu can instigate the activity of NO synthases, then induce a series of changes within cell and finally lead to the toxic effect on cells.

Nerve growth factors prevent glutamate toxicity in cortical neuronal cultures.

AIM: To determine if nerve growth factors (NGF) can protect against glutamate-induced cortical neuron damage. METHODS: Neuron viability and lactate dehydrogenase (LDH) efflux in the bathing medium in primary cultures from 17-d-old mouse fetal cortex were measured to assay NGF effect. Imaging of the calcium indicator dye Fura-2 was used to measure the [Ca2+]i. RESULTS: The LD50 for NGF-free glutamate was 0.2 mmol.L-1 (95% confidence limits 0-1.6 mmol.L-1). In the presence of NGF 60 micrograms.L-1, 59% of the neurons survived in glutamate 1.6 mmol.L-1. The protective effect afforded by NGF was maximal at 60 micrograms.L-1, at which it prevented the elevation in [Ca2+]i. CONCLUSION: NGF protect cortical neurons against glutamate-induced toxicity via "stabilizing" [Ca2+]i level or suppression of the rise in [Ca2+]i.

Effects of nitrendipine on capacity of calcium binding of erythrocyte membrane and total intraerythrocyte calcium content in SHR rats.

AIM: To study the effect of nitrendipine (Nit) on the capacity of calcium binding of erythrocyte membrane and total intraerythrocyte calcium content in spontaneous hypertensive rats (SHR). METHODS: Systolic blood pressure (SBP) of the conscious rats was monitored by tailcuff method with a BP and HR recorder for MRS-III rat. Erythrocyte membrane was prepared according to modified Bing's method. Calcium binding of membrane and total intraerythrocyte calcium content was determined by an automatic absorption spectrophotometer. The membrane protein was determined with a colorimetric method. RESULTS: Nit (ig 10 mg.kg-1 qd x 20 d) induced a significant reduction in total intraerythrocyte calcium content (169 +/- 18 vs 87 +/- 14 mumol/L cell, P < 0.01) accompanied by a marked fall of SBP (27.1 +/- 2.5 vs 16.7 +/- 1.0 kPa, P < 0.01) but exerted no influence on the capacity of calcium binding of erythrocyte membrane under incubation in CaCl2(0) (basal calcium binding) or 40 mmol.L-1 (maximal calcium binding) (21.9 +/- 2.3 vs 22.7 +/- 2.1 and 55 +/- 14 vs 53 +/- 23 mumol/g protein, respectively, P > 0.05). CONCLUSION: The antihypertensive effect of Nit is related to the reduction of intracellular calcium and possibly have no direct relation to the capacity of calcium binding of cell membrane.

[Effects of morphine on monosodium glutamate neurotoxicity and its mechanism].

The enhancing effects of morphine on monosodium glutamate (MSG) neurotoxicity and its blocking by naloxone were studied through morphological observation, together with detection of concentrations of intracellular free Ca2+ ([Ca2+]i) by Ca2+ indicator Fura-2/AM and lactate dehydrogenase (LDH) efflux in the bathing medium in primary cultures from 14-17 d old mouse fetal cortex. It was found that 10 min pre-incubation of young cortical neurons (7 day in vitro) with morphine 10(-7) or 10(-6) mol.L-1 substantially increased LDH release from 105.7% +/- 19.0% (treated with MSG alone) to 194.5% +/- 17.7% and 214.0% +/- 9.5% respectively after exposure to MSG 0.1 mmol.L-1, but pre-incubation with morphine (10(-7) or 10(-6) mol.L-1) plus naloxone (0.1 mmol.L-1) reversed the LDH release after treatment with the same concentration of MSG. Morphine (10(-7) or 10(-6) mol.L-1) produced little elevation of [Ca2+]i. However, when combined with MSG (0.1 mmol.L-1) morphine elevated the [Ca2+]i level much more than MSG alone. These results suggest that morphine markedly enhances excitotoxic neuron damage, which can be reversed by naloxone. Overloading of intracellular Ca2+ may be a simultaneous pathological mechanism underlying the neuronal damage and death that occur in excitatory toxicity.

[Effects erythropoietin on experimental anemia in rats with chronic renal failure].

Erythropoietin (EPO) is a glycoprotein hormone secreted by human kidney cells. Human EPO was induced from human embryo kidney cells, isolated and purified from medium by biochemical method in our laboratory. The hypoproliferative anemia in chronic renal failure (CRF) has been assumed to be the result of decreased EPO production by the damaged kidney and of the shortening of the survival of erythrocytes. In this study, CRF anemia was formed 9 weeks after the removal of five-sixths of the renal mass of rats. These anemic rats were divided into 6 groups: treated with different dosages of EPO or physiological saline. The results indicate that EPO has apparent effects on anemia in rats with CRF. It may stimulate erythropoiesis and improve the anemia state of rats with CRF. Hematological parameters (RBC, Hb, PLT, Ht and Rt) may be reverted to normal levels (P less than 0.001). The level of BUN and Cr were significantly decreased. The optimum dose of EPO was 1000 U/kg. All these results show that injection of EPO has therapeutic effect on anemia in rats with CRF. EPO showed no effect on normal rats.

Rat liver insulin mediator which stimulates pyruvate dehydrogenase phosphate contains galactosamine and D-chiroinositol.

It has been established that insulin treatment of cells, isolated plasma membranes, or whole animals leads to the generation of low molecular weight mediators which serve as intermediates in the signalling pathway. At least two distinct classes of mediator have been described, based on differences in apparent molecular weight, isoelectric point and biological activity (Cheng, K., and Larner, J. (1985) Ann. Rev. Physiol. 45, 407-424). Recently, Saltiel's (Saltiel, A.R., and Cuatrecasas, P. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 5793-5797) and Mato's (Mato, J.M., Kelly, K.L., Abler, A., and Jarett, L. (1987) J. Biol. Chem. 262, 2131-2137) laboratories have described an insulin "modulator" which was apparently derived from glycosylphosphoinositol linker, similar to those known to anchor proteins to the external surface of the cell membrane (Low, M.G. (1987) Bioch. J. 244, 1-13). In this paper, we report that highly purified preparations of the insulin mediator which stimulates pyruvate dehydrogenase phosphatase contain mannose, galactosamine, and D-chiroinositol. These determinations are based upon analyses using paper chromatography and gas chromatography/mass spectroscopy. Nitrous acid deamination of the mediator resulted in release of inositol phosphate, indicating that the galactosamine and D-chiroinositol are linked. Although the presence of chiroinositol in modulator from H35 hepatoma cells has been recently reported (Mato, J.M., Kelly, K.L., Abler, A., Jarett, L., Corkey, B.E., Cashel, J.A., and Zopf, D. (1987) Bioch. Biophys. Res. Comm. 146, 764-770), the optical identity of the inositol remained unknown until the present report. Likewise, the presence of galactosamine rather than glucosamine in insulin mediator is a novel finding. These findings, coupled with those of Saltiel and Mato's groups, provide clear evidence for the existence of multiple forms of insulin mediators. Additionally, the results presented here afford further confirmation for the formation of insulin mediators from glycosyl-phosphoinositol linkers.