The Discriminative Stimulus Properties of Acute Ethanol Withdrawal (Hangover) in Rats

Twenty male Sprague-Dawley rats were trained to discriminate pentylenetetrazole (PTZ, 15 mg/kg, intraperitoneally) from saline (SAL) under a drug discrimination procedure. Test sessions were conducted with 10 randomly selected subjects. Tests with various doses of PTZ resulted in a dose-dependent increase in the percentage of total session responses emitted on the PTZ-appropriate lever without a significant change in response rates across a wide range of test PTZ doses. Rats did not generalize the PTZ stimulus to ethanol (ETOH) up to ETOH test doses that completely suppressed responding. High acute ETOH doses (2, 3, and 4 g/kg) administered at various time points prior to discrimination test sessions engendered responding on the PTZ-appropriate level in a quantitative fashion, that was dose- and time-dependent. This acute ETOH delayed effect from these high doses replicates our previously published study using a Drug 1-Drug 2 discrimination task with Chlordiazepoxide and PTZ. More importantly, we suggest that the present behavioral assay may be a sensitive animal analogue of human "hangover" phenomena.     

Hemicholinium-3 impairs spatial learning and the deficit is reversed by cholinomimetics

The effects of hemicholinium-3 (HC-3) on spatial discriminaton learning were studied. Rats were equipped with indwelling cannulae in the right lateral ventricle and, following recovery, were trained on a two platform spatial discrimination task in a water maze. In this task a visible escape platform remains in a fixed position in the pool during a single training session, whilst the location of an identical float (which affords no escape) is randomly varied. For each session the location of the fixed escape platform was changed and the rats were retrained to criterion following pretreatment either with artificial cerebrospinal fluid (CSF) or HC-3 (2.5, 5.0 g/rat/ICV) 1 h before training. Each rat received every treatment according to a latin square design. The results showed that spatial learning was dose dependently impaired by HC-3, choice accuracy being reduced to chance levels by the higher dose. There was no evidence of motoric difficulty, as choice latencies were not significantly increased. Experiments were then conducted to test for reversal of the deficit using a range of psychotropic drugs. Rats were treated with CSF or HC-3 (5 g/rat ICV) 60 min prior to testing and test drugs were injected 15 min before testing. Some doses of physostigmine (46–460 g/kg/SC) and tetrahydroaminoacridine (THA) (2.2–10 mg/kg/SC) reversed the spatial learning deficit. The muscarinic agonists arecoline (0.046–1 mg/kg/SC), aceclidine (1–10 mg/kg/SC), oxotremorine (30–100 g/kg/SC) and RS-86 (0.46, 1.0 g/kg/SC) were also effective. Pilocarpine (0.22–2.2 mg/kg/SC) showed marginal activity and isoarecoline (4.6–10 mg/kg/SC) was inactive. Nicotine (0.32, 1, 3.2 mg/kg/SC) and piracetam (10, 30, 100 mg/kg IP) were also inactive. The ₂ agonist, clonidine (46, 100 g/kg SC) and the antagonist idazoxan (32, 100 g/kg SC) were also inactive. Learning deficits were not reversed by haloperidol (20, 60 g/kg), amphetamine (0.1, 0.46 mg/kg), the selective 5-HT_1A agonist 8-OH-DPAT (30, 100 g/kg) or by the benzodiazapine antagonist ZK 93426 (1, 3.2, 10 mg/kg). The results show that forebrain Ach depletion by HC-3 impairs spatial discrimination learning and these deficits are reversed by cholinesterase inhibitors and some muscarinic receptor agonists. Some degree of pharmacological selectivity is indicated by the failure of a range of other drugs to reverse the impairments.     

Relative motion of lung and chest wall promotes uniform pleural space thickness

The pleural space is modeled in two dimensions as a thin layer of fluid separating a deformable membrane and a rigid surface containing a bump. We computed the steady-state membrane configuration and fluid pressure distribution during relative sliding of the two surfaces. For physiologically relevant values of membrane tension, shear flow-induced pressures near the bump and far-field pressure gradients are similar to those measured in vivo within the pleural space (e.g. Lai-Fook et al.) [J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 56 (1984) 1633-1639]. Deformation of the membrane over the bump suggests that the pressure field generated by the sliding motion promotes an even layer of fluid in the pleural space, preventing asperities from touching. Results also suggest a possible mechanism for pleural fluid redistribution during breathing, whereby irreversible fluid motion is associated with the deformability of the membrane.     

Influence of neonatal sympathectomy on proximal renal resistance artery function in spontaneously hypertensive rats

Renal transplantation experiments have shown that the kidney contributes to chronic sympathectomy-induced arterial pressure reduction in spontaneously hypertensive rats (SHR). The underlying mechanisms are currently unclear but may include alterations in the function of small renal arteries. Neonatal SHR were sympathectomized by intraperitoneal guanethidine injections and removal of adrenal medullary tissue. Controls were sham- or hydralazine-treated. At 12 weeks of age, distal interlobar artery segments were investigated using small-vessel wire myography. Vessels from sympathectomized animals showed increased sensitivity to noradrenaline (NE). Vasopressin- and endothelin-1-induced vasoconstriction was similar in all groups (as reflected by the pD₂, i.e. –logEC₅₀, where EC₅₀ is the molar concentration of agonist eliciting a half-maximal response). Maximum vasopressin-induced tension was similar in all groups while endothelin-1-induced maximum tension was significantly higher in sympathectomized than in sham-treated SHR. The sensitivity of NE-induced vasoconstriction to extracellular Ca²⁺ did not differ between groups while sensitivity to L-type Ca²⁺ channel activation was significantly higher in both sympathectomized and hydralazine-treated animals than in sham-treated animals. Endothelium-dependent and independent vasodilation were similar in all groups. Sequential blockade of NO-synthase and cyclooxygenase had similar effects in all groups. In conclusion, neonatal sympathectomy does not induce any changes in the function of isolated proximal renal resistance arteries from SHR that could explain the blood pressure lowering effect of a kidney graft from sympathectomized SHR.     

Neck proprioception compensates for age-related deterioration of vestibular self-motion perception

Vestibular functions are known to show some deterioration with age. Vestibular deterioration is often thought to be compensated for by an increase in neck proprioceptive gain. We studied this presumed compensatory mechanism by measuring psychophysical responses to vestibular (horizontal canal), neck and combined stimuli in 50 healthy human subjects as a function of age (range 15–76 years). After passive horizontal rotations of head and/or trunk (torso) in complete darkness (dominant frequencies 0.05, 0.1, and 0.4 Hz), subjects readjusted a visual target to its remembered prerotational location in space. (1) Vestibular-only stimulus (whole-body rotation); subjects' responses were shifted towards postrotatory body position, this only slightly at 0.4 Hz and pronounced at 0.1 and 0.05 Hz. These errors reflect the known physiological drop of vestibular gain at low rotational frequency. They exhibited a slight but significant increase with age. (2) Neck-only stimulus (trunk rotated, head stationary); the responses showed errors similar to those upon vestibular stimulation (with offset towards postrotatory trunk position) and this again slightly more with increasing age. (3) Vestibular-neck stimulus combination during head rotation on stationary trunk; the errors were close to zero, independent of stimulus frequency and the subjects' age. (4) Opposite stimulus combination (trunk rotated in the same direction as the head, but with double amplitude); the errors were clearly enhanced, essentially reflecting the sum of those with vestibular-only and neck-only stimulation. Taken together, we find a parallel increase in neck- and vestibular-related errors with age, in seeming contrast to previous studies. We explain our and the previous findings by a vestibular-neck interaction model in which two different neck signals are involved. One neck signal is used, in combination with the vestibular signal, for estimating trunk-in-space rotation. It is internally shaped to always match the vestibular signal, so that these two signals cancel each other out when summed during head rotation on stationary trunk. Because of this matching, perceived trunk stationariness during head rotation on the stationary trunk is independent of vestibular deterioration (related to stimulus frequency, age, ototoxic medication, etc.). The other neck proprioceptive signal, coding head-on-trunk rotation, is superimposed on the estimate of trunk-in-space rotation, thereby yielding a notion of head-in-space. This neck signal remains essentially unchanged with vestibular deterioration. Generally, we hold that the transformation of the vestibular signal from the head down to the trunk proceeds further to include the hip and the legs as well as the haptically perceived body support surface; by this, subjects yield a notion of support kinematics in space. As a consequence, spatial orientation is impaired by chronic vestibular deterioration only to the extent that the body support is moving in space, while it is unimpaired (determined by proprioception alone) during body motion with respect to a stationary support. Electronic Publication     

选择性肠道清洁法对重症烫伤大鼠肠源性内毒素血症的影响

本实验采用大鼠４０％Ⅲ°烫伤模型，初步观察了选择性肠道清洁法（ＳＤＤ）对肠源性内毒素血症的防治效果。结果发现，防治组动物门、体循环内毒素水平伤后均显著降低（Ｐ＜０．０５～０．０１），各段肠腔内游离内毒素含量较烫伤对照组下降９９．５％以上。且肠道细菌易位率致伤１～５天都明显减少，回肠粘膜二胺氧化酶活性逐渐恢复。防治组大鼠严重烫伤５天存活率提高２６．７％（Ｐ＜０．０５）。本结果提示，该方法对于重症烫伤大鼠肠源性内毒素血症具有显著防护效应，并能抑制肠道细菌的移居与减轻肠粘膜的进一步损害。因此，及早进行ＳＤＤ可能有助于烧伤后肠源性感染及其它并发症的防治。     

终末期肝病模型评分在原发性肝癌合并肝硬化脾功能亢进外科治疗中的作用

目的 探讨终末期肝病模型(MELD)评分评估肝储备功能在原发性肝癌合并肝硬化脾功能亢进中确定手术适应证的应用价值.方法 对2001年1月至2007年1月间行肝癌切除联合脾切除(联合术)治疗的40例原发性肝癌合并肝硬化脾功能亢进患者的临床资料进行回顾性分析.通过MELD评分与Child-Pugh分级比较,结合临床资料及术后并发症分析,确定这一方法在评估肝储备功能中的作用.结果 同一Child-Pugh分级的患者MELD评分结果并不一致,在各级别间有交错现象.术后发生肝功能衰竭组(6例)的MELD评分均值为(24.6±6.6).未发生肝功能衰竭组(34例)的MELD评分均值为(16.3±8.5),差异有统计学意义(P<0.05).根据MELD评分分为A组16例(MELD评分<10),B组17例(MELD评分10-20),C组7例(MELD评分>20).A组术后肝功能衰竭发生率为0,B组为11.8%(2/17),C组为57.1%(4/7),差异有统计学意义(P<0.05).根据Child-Pugh分级分为Ⅰ级26例,Ⅱ级14例.Ⅰ级术后肝功能衰竭发生率为15.4%(4/26),Ⅱ级为14.3%(2/14),差异无统计学意义(P>0.05).结论 MELD评分能够较为客观地反映肝储备功能,对外科术式的选择、手术时机的确定有一定的参考作用.     

Elastohydrodynamic separation of pleural surfaces during breathing

To examine effects of lung motion on the separation of pleural surfaces during breathing, we modeled the pleural space in two dimensions as a thin layer of fluid separating a stationary elastic solid and a sliding flat solid surface. The undeformed elastic solid contained a series of bumps, to represent tissue surface features, introducing unevenness in fluid layer thickness. We computed the extent of deformation of the solid as a function of sliding velocity, solid elastic modulus, and bump geometry (wavelength and amplitude). For physiological values of the parameters, significant deformation occurs (i.e. bumps are 'flattened') promoting less variation in fluid thickness and decreased fluid shear stress. In addition, deformation is persistent; bumps of sufficient wavelength, once deformed, require a recovery time longer than a typical breath-to-breath interval to return near their undeformed configuration. These results suggest that in the pleural space during normal breathing, separation of pleural surfaces is promoted by the reciprocating sliding of lung and chest wall.     

Mathematical modelling of the growth processes in the developing chick wing bud

This paper illustrates how a simple geometric model resembling the shape of the chick wing bud at an early growth stage can be mathematically expanded to simulate subsequent growth characteristics of the developing bud. The model was tested against several sets of experimental data and gave an acceptable representation of growth over the range considered. Representing growth patterns in this form enables the determination of differential growth characteristics in different parts of the bud and provides boundary constraints which will play an important part in the eventual evaluation of internal growth mechanisms.     

Changes in myocardial pyrimidine nucleotide levels following repeated injections of isoproterenol in rats

Changes which might lead to the initiation of cardiac hypertrophy include possible variations in the dynamics of nucleotides. In the experiments reported in this paper, changes in the pool sizes of adenine, uracil and cytosine nucleotides were observed during the initial phase of cardiac overload.Repeated subcutaneous injections of isoproterenol (ISO) (5 mg·kg^–1 body weight, s.c.) were performed so as to produce symmetric cardiomegaly in rats. Under these conditions, the dry weight of the heart, on the fifth day of dialy injections of ISO, had increased by 43% and the RNA concentration by 39%. There was no significant change in the DNA concentration. No further changes in weight or in DNA and RNA concentrations were recorded from the fifth to the tenth day of treatment.Changes in UTP and ATP were carefully monitored during the first days following ISO application. The levels of both nucleotides decreased sharply at first. The ATP level remained below the control value for at least 48 h while the UTP level was rapidly restored and a further increase occurred resulting in a maximal enlargement of 82% after the 12th h. At the same time, the uracil nucleotide pool and the cytosine nucleotide pool had increased by 76% and 101%, respectively, while the adenine nucleotide content of the myocardium remained 15% below control level. Repeated injections of ISO induced effects on ATP and UTP levels which were similar in direction but attenuated.The significance of an increase in the pyrimidine nucleotide pools in relation to nucleic acid synthesis is discussed.