The in vivo availability of gentamicin when admixed with total nutrient solutions: a comparative study

The relative in vivo availability of gentamicin when administered by two different intravenous methods was evaluated in patients treated in a surgical intensive care unit in a randomized, prospective, crossover study. Each patient received gentamicin therapy via intravenous piggyback (IVPB) and in-line burette (ILB) methods. In the IVPB method, the drug was mixed in 5% dextrose in water (D5W) and infused intermittently. In the ILB method, the drug was mixed using the patient's total nutrient admixture (TNA) solution as the diluent in an ILB, which was inserted between the TNA bottle and its administration set and infused intermittently. A serial sampling of four sets of serum concentrations of the gentamicin was obtained. Pharmacokinetic parameters (Kel, Vd, and a maximum serum concentration) were calculated from the four sets of concentrations collected per patient. The IVPB method yielded mean values of Kel, Vd, and C1.5mg/kg of 0.13 hr-1, 0.39 liter/kg, and 5.1 micrograms/ml, respectively. The ILB method yielded mean values of Kel, Vd, and C1.5mg/kg of 0.14 hr-1, 0.34 liter/kg, and 5.6 micrograms/ml, respectively. A t-test for paired samples was applied to these mean values. Significant difference was not found (p greater than 0.05). The intermittent infusion of gentamicin, using TNA as the diluent and an ILB, produced equivalent serum concentrations when compared with D5W as the diluent.     

Lateral Paracapsular GABAergic Synapses in the Basolateral Amygdala Contribute to the Anxiolytic Effects of ��3 Adrenoceptor Activation

Norepinephrine (NE) is known to play an integral role in the neurobiological response to stress. Exposure to stressful stimuli increases NE levels in brain regions that regulate stress and anxiety, like the basolateral amygdala (BLA). NE is thought to increase excitability in these areas through α- and β-adrenoceptors (ARs), leading to increased anxiety. Surprisingly, recent studies have shown that systemic β3-AR agonist administration decreases anxiety-like behaviors, suggesting that β3-ARs may inhibit excitability in anxiety-related brain regions. Therefore, in this study we integrated electrophysiological and behavioral approaches to test the hypothesis that the anxiolytic effects of β3-AR agonists may be mediated by an increase in BLA GABAergic inhibition. We examined the effect of a selective β3-AR agonist, BRL37344 (BRL), on GABAergic synapses arising from local circuit interneurons and inhibitory synapses originating from a recently described population of cells called lateral paracapsular (LPCS) interneurons. Surprisingly, BRL selectively enhanced LPCS-evoked inhibitory postsynaptic currents (eIPSCs) with no effect on local GABAergic inhibition. BRL also had no effect on glutamatergic synaptic excitation within the BLA. BRL potentiation of LPCS eIPSCs was blocked by the selective β3-AR antagonist, SR59230A, or by intracellular dialysis of Rp-CAMPS (cAMP-dependent protein kinase inhibitor), and this enhancement was not associated with any changes in spontaneous IPSCs or LPCS paired-pulse ratio. BRL also increased the amplitude of unitary LPCS IPSCs (uIPSCs) with no effect on uIPSC failure rate. Finally, bilateral BLA microinjection of BRL reduced anxiety-like behaviors in an open-field assay and the elevated plus-maze. Collectively, these data suggest that β3-AR activation selectively enhances LPCS, but not local, BLA GABAergic synapses, and that increases in LPCS-mediated inhibition may contribute to the anxiolytic profile of β3-AR agonists.     

黄柏及中成药中小檗碱和巴马亭的高效液相色谱法测定

本文以正相高效液相色谱法,用窗口图解技术对色谱条件进行了优化。对黄柏及其中成药中的有效成分——小檗碱、巴马亭的提取、测定条件、标准曲线进行了研究。并对两种含黄柏的中成药样品进行了分析。其中小檗碱的回收率均在97%以上,巴马亭的回收率均在96%以上。     

安宫牛黄丸中小檗碱的HPLC法测定

本文报道用HPLC法测定黄连及含黄连中成药安宫牛黄丸中小檗碱型生物碱。实验结果表明选用硅胶柱为固定相,以醋酸乙酯—甲酸—乙醇(15:3:2)为流动相,能使样品中四种小檗碱型的生物碱获得最佳分离。用此法测得不同厂家生产的安宫牛黄丸中盐酸小檗碱的含量为0.331～0.456%,平均回收率为97.23%,变异系数为1.2%。     

Effects of 3'-deamino-3'-(3-cyano-4-morpholinyl)doxorubicin and doxorubicin on the survival, DNA integrity, and nucleolar morphology of human leukemia cells in vitro

The potential mechanisms of the extremely potent anthracycline analogue 3'-deamino-3'-(3-cyano-4-morpholinyl)doxorubicin (MRA-CN) have been compared with those of doxorubicin (DOX) by examination of drug effects on colony formation, macromolecular synthesis, DNA integrity, and ultrastructure of human leukemia cells in vitro. Following a 1-h exposure, MRA-CN was found to be 1400-fold more cytocidal than DOX which correlated with the drugs' inhibitory effects on DNA and total RNA synthesis. Treatment with MRA-CN resulted in a dose-dependent production of DNA interstrand cross-links as quantified by alkaline elution. One-h treatments with DOX or 3'-deamino-3'-(4-morpholinyl) doxorubicin (the non-cyano-containing analogue of MRA-CN) produced no DNA-DNA cross-links; rather they produced protein-concealed DNA single-strand breaks. After removal of MRA-CN, the DNA of KBM-3 cells displayed time-dependent fragmentation as indicated by rapid DNA filter elution during the pH 10 lysis step which preceded pH 12 elution. Within 4 h of MRA-CN exposure (10 nM, 1 h), 50% of the cellular DNA was in the lysis fraction. By 24 h, all the cellular DNA was in this fraction. MRA-CN (10 nM), 3'-deamino-3'-(4-morpholinyl)doxorubicin (1 microM), and actinomycin D (1 microM), but not DOX (3 mircroM), each produced distinctive nucleolar macrosegregation, indicating an effect on rRNA synthesis. The alpha-CN substituent on the morpholinyl moiety of MRA-CN appears to be responsible for the unique antitumor potency of this anthracycline. Nucleolar macrosegregation is probably associated with the morpholinyl moiety and is independent of the alpha-CN substituent.     

Mesoatrial shunts for Budd-Chiari syndrome and inferior vena cava thrombosis: angiographic and hemodynamic evaluations

When inferior vena caval obstruction complicates the Budd-Chiari syndrome, conventional portosystemic shunts are not possible. The mesoatrial shunt has been devised to enable portal and sinusoidal decompression in these patients. Findings in 12 patients with Budd-Chiari syndrome and inferior vena caval obstruction in whom a mesoatrial shunt was performed are reported. Preoperative inferior vena cavography with pressure measurements is essential to determine the appropriate shunt procedure. Postoperatively, shunt patency is assessed with superior mesenteric arterial portography. Where possible, transvenous catheterization of the shunt is performed to confirm patency and assess hemodynamic function.