The isolated spinal cord-skin preparation of the newborn rat and effects of some algogenic and analgesic substances

We have developed an isolated spinal cord-skin preparation of the newborn rat. The spinal cord together with a piece of skin connected to the cord by the saphenous nerve was isolated from 1- to 4-day-old rats and separately superfused with artificial cerebrospinal fluid in two neighbouring chambers. Potentials were recorded extracellularly from the third lumbar ventral root. Application of capsaicin (0.5-2 μM) or KCl (60–350 mM) with brief pressure pulses to the perfusion bath of the skin evoked a depolarizing response of 20- to 40-s duration in the ventral root. The response was depressed by [Met⁵]enkcphalin (0.03–3 μM). morphine (0.1–2 μM) and a tachykinin antagonist, [D-Arg¹,D-Trp^7,9,Leu¹¹] substance P (spantide), 1–10 μM), applied to the spinal cord by superfusion, whereas the response was augmented by centrally administered calcitonin gene-related peptide (0.1–0.2 μM) or bicuculline (0.5–1 μM).     

Preparation and Characterization of a Murine Monoclonal Antibody (MDR3M) Reactive with mdr3 Gene Product

A murine monoclonal antibody (MDR3M) (isotype: IgM) reactive with mdr3 gene product was generated by immunizing mice with mdr3 -specific peptide (H₂N-¹²WRPTSAEGDFELGISSKQKRKKTKTVKMI⁴¹G-COOH) and hybridizing the primed mouse splenic B cells with X63-Ag8,6.5.3 mouse plasmacytoma cells. MDR3M did not cross-react with mdr1 gene product. This monoclonal antibody may be useful for analyzing the role of mdr3 gene product in cells and tissues.     

Pharmacokinetics of reboxetine in healthy volunteers. Single oral doses,linearity and plasma protein binding

The pharmacokinetics of reboxetine, a new antidepressant agent, were found to be close to linear in a crossover study comparing administration of single 2, 3, 4 and 5 mg capsule doses in 15 healthy male volunteers, and in the same study the capsules were bioequivalent to the proposed therapeutic tablet formulation (4mg). Kinetic analysis was based on HPLC assay of reboxetine in plasma and urine collected up to 72 h after each administration. Plasma levels indicated a rapid absorption (t_max?2h) and an elimination half-life of about 13 h. Clearance and volume of distribution were modest (ratios to bioavailability: CL/F?29 mL min^?1; V_z/F?32L); urinary excretion was ～9% of dose, corresponding to a renal clearance of only 3 mL min^?1 (a value consistent with the rate of glomerular filtration of unbound drug). In vitro, binding to plasma proteins, estimated from radioactivity levels following dialysis of ¹⁴C-labelled reboxetine, appeared to be dominated by α₁-acid glycoprotein without marked saturation up to plasma concentrations of over 500 ng mL^?1 (2.8–3.1% unbound with human plasma from three additional volunteers; 1.8–2.0% for 2gL^?1 orosomucoid α₁-acid glycoprotein, and 46.4–47.4% for 40 gL^?1 albumin), whilst the mean C_max in the current study was much lower (164 ng mL^?1 after a 5 mg dose).     

阻塞性睡眠呼吸暂停综合征患者肾功能和心钠素的变化分析

目的探讨病人肾功能、心钠素(ANP)的含量变化及经鼻持续气道正压(nCPAP)治疗对阻塞性睡眠呼吸暂停综合征(OSAS)患者的影响。方法选择经多导睡眠图(PSG)确诊为中、重度的OSAS患者11例为试验组,PSG检查正常者14例为对照组，试验组给予nCPAP治疗，分别测定其血尿肌酐、尿量、尿β2-微球蛋白(β2-MG)、血浆心钠素(ANP)，并计算出内生肌酐清除率(Ccr)，比较试验组与对照组及试验组治疗前后各项指标的差异。结果试验组与对照组比较，Ccr,尿β2-MG差异无显著性，经nCPAP治疗后两指标也无明显改变；试验组的夜尿量、血ANP含量显著高于对照组，nCPAP治疗后上述指标均较治疗前明显下降。结论OSAS患者夜尿量增多可能与ANP增加有关，这种增高可以被nCPAP治疗所纠正。     

重度烧伤患者休克期血浆B型钠尿肽含量变化及意义

Objective To study the plasma content of B-type natriuretic peptide (BNP) in patients with severe burn during shock stage and probe its clinical significance. Methods Forty-two patients aged 18-60 years, with total burn surface area ≥30%TBSA or full-thickness burn area ≥10% TBSA, hospital-ized within 4 hours after burn, were divided into A group (with total burn surface area 30% -50% TBSA or full-thickness burn area 10% -20% TBSA, n = 21 ), and B group (with total burn surface area 50% TB-SA or full-thickness burn area > 20% TBSA, n = 21 ). Twenty patients admitted during the same time for plastic surgery were enrolled as control group. The plasma levels of BNP, creatine kinase (CK), CK-MB, troponin I (Tnl) of all patients were determined on admission. The levels of BNP, Tnl and fluid resuscita-tion volume were examined at 8, 16, 24, 48 post burn hour (PBH) in A and B groups. Analysis of correla-tion between BNP and fluid resuscitation volume was performed. Results On admission: BNP level in A group (68±19 ng/L) and B group (99±38 ng/L) , respectively, was increased as compared with that in control group (17±7 ng/L, P <0.01 ). Tnl level in A group (2.13±0.67 μg/L) and B group (2.98± 0.58μg/L), respectively, was increased as compared with that in control group (0.12 ± 0.03 μg/L, P < 0.01). There was no obvious difference in CK, CK-MB levels among A, B, and control groups ( P > 0.05). BNP levels in A, B groups continuously rose during 8 - 48 PBH, and they were positively correlated with fluid resuscitation volume. TnI level peaked at 24 PBH, and decreased at 48 PBH. Conclusions The plasma level of BNP is sensitive to reflect changes in myocardial ischemia and hypoxia as a rise in level of TnI in shock stage of severe burn, and it was positively correlated with fluid resuscitation volume. BNP can be used to guide fluid resuscitation during shock stage.     

Pharmacokinetics of orally administered hexobarbital in plasma and saliva of healthy subjects

Hexobarbital (HB) concentrations were determined in plasma and saliva of 8 healthy subjects, following oral administration of 500 mg HB-Na. Mean plasma half-lives were 3.2 +/- 0.1 h, and salivary half-lives 3.3 +/- 0.2 h. Mean plasma clearance was 22.9 +/- 2.3 1 h-1. There was a linear relationship between HB concentrations in saliva and plasma (r = 0.92). Mean salivary levels were 34 per cent of plasma levels. Salivary pH was constant throughout the experiment, 7.06 +/- 0.09. There was an inconsistent tendency of the saliva over plasma ratios to increase as a function of time. The percentage of protein binding calculated from saliva over plasma ratios was in reasonable agreement with in vitro data of equilibrium dialysis, 64.1 +/- 2.6 per cent and 65.9 +/- 0.8 per cent, respectively. The experiment was repeated in 4 subjects, and considerable intraindividual differences were shown to exist in saliva over plasma ratio, half-lives, and protein binding. It was concluded that HB elimination half-lives can relatively accurately be determined from salivary concentrations. Oral plasma clearance can only be estimated if the individual saliva over plasma ratios are known; this would require the taking of at least one blood sample during the experiment. When employing HB as a model substrate for drug metabolizing enzyme activity in vivo, the determination of its pharmacokinetic parameters, particularly oral plasma clearance as a reflection of cytochrome P-450 activity, cannot be achieved by taking saliva samples only.     

Plasma protein binding of furosemide in the elderly

Summary The protein binding of furosemide was investigated in plasma from 22 old and 11 young subjects by equilibrium dialysis. The unbound fraction of furosemide was 3.16% in plasma from the elderly and 1.71% in plasma from the young. A significant correlation was found between the unbound fraction of furosemide and the plasma concentration of albumin. The average number of binding sites was 3.8 (elderly) and 2.7 (young) 10^–6 mol/g albumin. The average association constant (K) was 4.3 (elderly) and 4.2 (young) 10⁵ M^–1. By increasing the concentration of furosemide up to 200 µg/ml buffer the unbound fraction of the drug rose to 5.2% (elderly) and 3.5% (young).     

A theophylline dosage regimen which reduces round-the-clock variations in plasma concentrations resulting from diurnal pharmacokinetic variation

Summary Slower drug absorption at night can leave residual drug from an evening dose of a sustained-release product remaining to be absorbed at the time of the next morning's dose, thereby giving higher plasma concentrations of the drug during the day than the night.When a capsule product releasing theophylline over 12 h after a morning dose was given repetitively at 8 a.m. and 8 p.m. for 4 days, daytime plasma concentrations from 4 h to 8 h after the dose were about 40% greater than corresponding night-time concentrations, and the mean steady-state concentration during the night-time interval was only 81% of that during the daytime interval.Altering the regimen to one capsule at 12 noon and one at 10 p.m. eliminated all significant differences between a.m. and corresponding p.m. plasma concentrations of theophylline and between the mean steady-state concentrations for each of the interdose intervals within a day.     

Identification of the C-terminal flanking peptide of preprocholecystokinin in rat brain by a novel radioimmunoassay

The C-terminal flanking peptide of preprocholecystokinin (preproCCK) has been identified in extracts of rat brain using a novel radioimmunoassay. There is a single form of immunoreactive material on gel filtration, ion exchange and reversed-phase HPLC. The C-terminal preproCCK immunoreactivity had a similar pattern of distribution to CCK8 in different regions of rat brain. This assay should help in studies of neuronal CCK biosynthesis.