DOI [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCI] is a serotonin (5-HT1C/5-HT2) agonist, with potent cardiovascular effects. The purpose of the present studies was to determine the identity and location of the 5-HT receptor subtype(s) mediating the renin and blood pressure responses to DOI. Injection (i.p.) of DOI to conscious male rats elevated plasma renin activity in a dose-dependent manner. The 5-HT1C/5-HT2 antagonist ritanserin completely blocked the DOI-induced increase in plasma renin activity. In order to distinguish the 5-HT2- from the 5-HT1C- mediated effect of DOI, spiperone was administered before DOI. Low doses of spiperone (0.01 and 0.1 mg/kg, s.c.) significantly reduced the renin response to DOI. Because spiperone has a higher affinity for 5-HT2 than 5-HT1C receptors, these data suggest that DOI stimulates renin secretion through 5-HT2 receptors. To separate central from peripheral 5-HT receptors, we injected DOI into rats pretreated with saline or xylamidine, a 5-HT2 antagonist which does not cross the blood-brain barrier. Xylamidine produced a shift to the right and suppression of the maximal effect of DOI on plasma renin activity, suggesting a role for peripheral 5-HT2 receptors in the effect of DOI. On the other hand, i.c.v. administration of DOI, using doses lower than the peripherally effective doses, caused a significant elevation of plasma renin activity at 200 micrograms/kg. These experiments suggest that DOI's elevation of plasma renin activity has both peripheral and central sites of action.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
BACKGROUND: Developments in accelerator mass spectrometry (AMS) now permit
the determination of femtogram amounts of 26Al in blood and in various
tissues with good precision and free of external contamination. METHODS: In
the present study we used trace quantities of 26Al to investigate the
intestinal absorption and compartmentalization of aluminium in rats with
renal failure (Nx, 5/6 nephrectomy) and in pair- fed controls (C). Single
oral doses of 20 ng 26Al were administered to six animals in each group
and, subsequently, 24-h post-load 26Al was analysed in serum, urine, bone,
liver, and spleen by means of AMS. RESULTS: Serum concentrations of 26Al
were significantly lower in uraemic rats compared to controls, whereas
urinary excretion was comparable (Nx, 7.11 +/- 5.78 pg/day vs C, 9.46 +/-
6.10 pg/day), suggesting a higher fraction of ultrafiltrable serum 26Al in
uraemia. The target tissues of cellular transferrin-mediated 26Al uptake,
liver and spleen, tended to show a larger degree of aluminium accumulation
in controls (0.26 +/- 0.31 pg/g vs Nx, 0.14 +/- 0.10 pg/g and 0.37 +/- 0.27
pg/g vs Nx, 0.25 +/- 0.27 pg/g respectively). In contrast, in bone, a site
of extracellular aluminium deposition, 26Al concentrations were more
elevated in uraemia (1.22 +/- 0.59 pg/g vs C: 0.68 +/- 0.30 pg/g).
Estimated total 26Al accumulation in all measured target tissues was
significantly higher in uraemic rats (28.15 +/- 9.90 pg vs C: 17.03 +/-
7.03 pg) and total recovery of 26Al from tissue and urine was 26.58 +/-
6.74 pg in controls and 35.75 +/- 7.03 pg in uraemic animals, suggesting a
fractional absorption of 0.133% and 0.175% respectively. CONCLUSIONS: Our
data suggest that fractional absorption from a dietary level dose of 26Al
is about 0.13%. Compartmentalization occurs in transferrin-dependent target
tissues such as liver and spleen; however, in quantitative terms
extracellular deposition in bone is more important. Uraemia has a
significant effect on the intestinal absorption and compartmentalization of
aluminium. It enhances fractional absorption and increases subsequent
extracellular deposition of aluminium in bone. However, at the same time
uraemia does not increase transferrin-dependent cellular accumulation of
aluminium in liver and spleen.
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Adrenergic, cholinergic, and a variety of peptide neurotransmitters are known to modulate Ca currents in peripheral neurons. Using a protocol that allows for simultaneous assessment of effects on dihydropyridine (DHP)-sensitive and DHP-insensitive current components, we compared the actions of norepinephrine (NE), bethanechol (BeCh), and neuropeptide Y (NPY) on Ca currents in neonatal rat superior cervical ganglion neurons. Here, we show that these transmitters selectively depress the activity of DHP-insensitive Ca channels. Intracellular application of GTP-gamma-S, an activator of GTP-binding proteins, also exclusively affected the DHP-insensitive current, whereas 1,2-oleoylacetylglycerol (OAG), a protein kinase C (PKC) activator, depressed both the DHP-sensitive and DHP-insensitive currents. Pertussis toxin interrupted the coupling between NE and its effector, whereas three different inhibitors of PKC did not. Thus, we confirmed that the selective actions of the transmitters on Ca current appear to be mediated via GTP-binding proteins, but we found no evidence for direct involvement of PKC and conclude that the observed actions of OAG are distinct from those mediated by the neurotransmitters studied. 相似文献
Background: Many studies have shown in the efficacy of patient-controlled analgesia (PCA). However, it is not clear whether PCA has clinical or economic benefits in addition to efficient analgesia. The current study was designed to evaluate these issues by comparing PCA with regularly administered intramuscular injections of opioids after hysterectomy.
Methods: This prospective study included 126 patients who underwent abdominal hysterectomy and were randomly assigned to receive PCA or regularly timed intramuscular injections of morphine during a period of 48 h. Doses were adjusted to provide satisfactory analgesia in both treatment groups. Pain at rest and with movement, functional recovery, drug side effects, and patient satisfactory were measured using rating scales and questionnaires. The costs of PCA and intramuscular therapy were calculated based on personnel time and drug and material requirements.
Results: Comparable analgesia was observed with the two treatment methods, with no significant differences in the incidence of side effects or patient satisfaction. The medication dosage had to be adjusted significantly more frequently in the intramuscular group than in the PCA patients. The PCA did not favor a faster recuperation time compared with intramuscular therapy in terms of times of ambulation, resumption of liquid and solid diet, passage of bowel gas, or hospital discharge. The results of the economic evaluation, which used a cost-minimization model and sensitivity analyses, showed that PCA was more costly than regular intramuscular injections despite the fact that no costs for the pump were included in the analyses. Cost differences in nursing time favoring PCA were offset by drug and material costs associated with this type of treatment. 相似文献
OBJECTIVES: To assess the economics of patient-controlled analgesia (PCA) treatment versus regular intramuscular (i.m.) injections of opioid analgesia for pain management after hysterectomy. METHODS: Cost-minimization analysis was used based on the comparable pain control results achieved in the two treatment groups. Observations were taken of treatment-related events with personnel (mostly nursing) time implications during the trial. Times were then associated with these events in an independent study of personnel activity. Costs were linked by using average wage rates for the various personnel for the Montreal area during the time of the study. Drug and material costs were hospital acquisition costs for all items. The cost of the PCA pump itself was not included in the analysis. Several analyses were performed to test the sensitivity of the results to various assumptions. RESULTS: The results for total costs of the two therapies generally showed PCA to be more costly than regular i.m. injections despite no costs of the pump being included in the analyses. These results were robust with respect to changes in assumptions. Even when intentionally biasing the analysis against i.m. therapy, it was difficult to obtain results that favored PCA. CONCLUSIONS: Based upon the institutions and assumptions in this analysis, PCA offers no cost advantages over regular i.m. therapy in the pain management after hysterectomy. Regular i.m. injections provided less costly analgesia. 相似文献
PURPOSE: The present study was designed to examine the pharmacokinetics of a fluocinolone acetonide (FA) intravitreal implant in pigmented rabbits. METHODS: Pigmented rabbits were randomly assigned to receive either a 0.5 mg or 2.0 mg FA intravitreal implant (Retisert). Four animals were sacrificed per time point (2 hours; 2 weeks; and 3, 6, 9, and 12 months after implantation) for FA intraocular levels determination. RESULTS: In the vitreous, concentration of FA was relatively constant from the first time point, 2 hours, through 1 year, and dose-related, approximately seven- to eight-fold greater in the 2-mg implant. Concentrations of FA were generally higher in the vitreous (11-18 and 75-146 ng/g) and retina (42-87 and 224-489 ng/g) than in the aqueous humor (0.21-1.1 and 2.6-13.0 ng/g) for the 0.5- and 2-mg implants, respectively. Urine and plasma values were below the lower limit of quantitation (200 pg/mL) for all observations, indicating no evidence of systemic absorption. CONCLUSIONS: In this rabbit study, the Retisert provides relatively constant levels of FA in the posterior pole, which is consistent with previous reports of its clinical utility. 相似文献
STUDY OBJECTIVE: To compare hospital length of stay (LOS), weekly discharges, and days of antibiotic treatment with linezolid (intravenous with oral follow-up) and vancomycin (intravenous only). DESIGN: Multinational, randomized, phase III trial. SETTINGS: Hospitals in North America, Latin America, and Europe. PATIENTS: Four hundred sixty hospitalized patients with infections of known or suspected methicillin-resistant Staphylococcus species. INTERVENTION: Administration of linezolid or vancomycin. MEASUREMENTS AND MAIN RESULTS: For linezolid recipients, median LOS was 5 and 8 days shorter (p=0.05 and 0.003) in the complicated skin and soft tissue infection intent-to-treat (230 patients) and clinically evaluable (144) samples, and slightly but not significantly shorter in the overall intent-to-treat (460) and clinically evaluable (254) samples. In all samples, linezolid recipients had more discharges in the first week of treatment and fewer days of intravenous therapy than vancomycin recipients. CONCLUSION: Our results support linezolid's ability to reduce medical resource use. 相似文献
The combination of high-dose busulfan (16 mg/kg) and 200 mg/kg cyclophosphamide is gaining increasing significance as a preparative regimen prior to autologous, syngeneic, or allogeneic marrow transplantation. A new regimen of high-dose busulfan in conjunction with a reduced dose of 120 mg/kg cyclophosphamide has recently been described as a preparative regimen prior to allogeneic transplantation. To determine the drug-related nonhematologic toxic effects of this new regimen without confounding factors associated with allogeneic transplantation, we conducted a pilot study using this new regimen in 20 patients with acute myeloid leukemia (AML) in first remission prior to autologous unpurged marrow transplantation. All patients experienced transient non-life-threatening acute drug-related toxicity with skin reactions in 20 (100%), nausea and vomiting in 20 (100%), oral mucositis in 18 (90%), hepatic functional impairment in 17 (85%), hemorrhagic cystitis in three (15%), and generalized seizures in two (10%) of these patients, respectively. Two procedural, fatal complications resulted from infectious causes that were not directly related to the speed of hematopoietic reconstitution or the toxicity of the preparative regimen. The 3-year event-free survival estimate (55% +/- 11%) and probability of leukemic recurrence (38% +/- 11%) attained with this new regimen in recipients of autografts in first remission of AML are promising and challenge comparisons with preparative regimens employing combinations of cytotoxic agents or total body irradiation (TBI). 相似文献