益智灵对小鼠学习记忆的促进作用

采用一次性训练的被动回避反应—“Ｙ”电迷宫法，观察益智灵对亚硝酸钠和３０％乙醇致小鼠记忆障碍的改善作用，并与尼莫地平和神经生长因子的作用作了比较。３种药物对改善亚硝酸钠致记忆巩固障碍均有效。益智灵和神经生长因子还拮抗３０％乙醇致记忆再现障碍。另结果表明益智灵对正常小鼠学习行为有促进作用，其它两药未见有此作用。     

外源性睾酮对离体家兔阴茎海绵体的影响(英文)

AIM: To study the effects of exogenous excess of testosterone on the constricting effect of phenylephrine and en-dothelium-dependent and -independent relaxing effects of different agonists in the corpus cavemosum penis (CCP). METHODS: Specimens of the CCP were obtained from rabbits testosterone for 1 and 2 months and untreated for 2 months after testosterone-treatment for 2 months. Preparations were mounted between two parallel platinum electrodes in organ baths. Responses to phenylephrine, car-bachol, and sodium nitroprusside were obtained by adding the reagent cumulatively to the bath. RESULTS: The phenylephrine-induced contractions were decreased with no change in agonist potency (pD2 value) after both 1 and 2 month testosterone-treatment and did not return to control values in corpus cavernosum obtained from rabbits untreated for 2 months after testosterone-treatment for 2 months. Testosterone treatment for 1 or 2 months increased the endothelium-dependent relaxations induced by carbachol and decrea     

电脉冲化学治疗仪的研制

介绍一种高压电脉冲化学治疗仪的原理和结构。该仪器是通过高压脉冲电场对肿瘤细胞进行穿孔，在细胞膜上产生可恢复的微孔通道，使抗癌药物经该通道进入细胞内，达到治疗目的，该仪器由可编程脉冲发生器，高压可调稳压电源，高压功率开关和保护电路组成。     

Analysis of gastric electrical signals from surface electrodes using phaselock techniques Part 2—System performance with gastric signals

The 0·05 Hz (3 cycle/min) electrical activity from the human stomach was first recorded in 1922 by Alvarez, using electrodes placed on the skin. The major problem with surface electrode recording is the poor signal/noise ratio. The application of a phaselock system, using a smaller number of readily available integrated circuits, to this problem has been described and in the paper the performance of this system is discussed.     

Conditioning stimulus can influence an external urethral sphincter contraction evoked by a magnetic stimulation

AIMS: To study the effect of a conditioning stimulus on an external urethral sphincter (EUS)contraction evoked by a magnetic stimulation at different time intervals. METHODS: Seven healthy male volunteers underwent EUS pressure measurement. At baseline, magnetic stimulation of the lumbosacral spinal cord above the motor threshold was performed and evoked EUS pressure responses were recorded. The lumbosacral magnetic stimulation was repeated with same intensity, while a selective electrical dorsal penile nerve stimulation below the bulbocavernosus reflex (BCR) threshold was preceding at five different intervals (10, 20, 30, 50, 100 msec). The protocol was performed with empty and full bladder (BLA), and baseline responses were statistically compared to those with combined stimulation. RESULTS: When the dorsal penile nerve electrical stimulation preceded the lumbosacral magnetic stimulation by 20 msec (P=0.0048), 50 msec (P=0.0039), or 100 msec (P=0.0002), the amplitudes of the EUS pressure response with empty BLA were significantly reduced compared to lumbosacral magnetic stimulation alone. With a filled BLA, the amplitudes of the EUS were significantly reduced only at an interval of 50 msec (P<0.0001). CONCLUSIONS: A conditional sensory pudendal stimulation seems to have the capacity to inhibit the external urethral sphincter contraction induced by a magnetic stimulation. The inhibitory effect seems to depend on the latency between the peripheral and lumbosacral stimulation as well as on the degree of BLA filling. It remains to be proved if the neuromodulative effect of the conditional stimulus occurs at a spinal or supraspinal level.     

Sacral neuromodulation for refractory detrusor overactivity in women with an artificial urinary sphincter

PURPOSE: We assessed the efficacy of sacral neuromodulation as an alternative therapeutic option in women with an artificial urinary sphincter (AUS) who had de novo irritative urinary symptoms (urgency/frequency) refractory to conventional treatment. MATERIALS AND METHODS: Between 1984 and 2002 we implanted an AUS in 350 women and detrusor overactivity developed in 14. Six of the 14 patients responding positively to a percutaneous nerve evaluation test (greater than 50% subjective/objective improvement) were implanted with an S3 neuromodulator within 42.8 weeks (range 21 to 106) of AUS implantation. Followup included analysis of the voiding diary, a pad test and urodynamic assessment. RESULTS: After 30.5 months followup (range 14 to 40) 1 patient was dry, 4 were improved and treatment failed in 1. At 12 months mean voiding frequency daily had decreased from 17 (range 12 to 23) to 8 (range 4 to 12) and the mean number of leakages episodes daily had decreased from 14.7 (range 8.5 to 17) to 6 (range 4 to 10). Mean voided volume had increased from 121.7 (range 90 to 170) to 180 ml (range 120 to 225), mean first desire to void volume had increased from 117 (range 88 to 190) to 183 ml (range 130 to 275) and mean functional bladder capacity had increased from 325 (range 200 to 530) to 372 ml (range 250 to 580). Uninhibited bladder contractions had resolved in 4 of 5 patients. CONCLUSIONS: In women who already have an AUS with urge incontinence sacral neuromodulation can help resolve symptoms. Because this therapy does not compromise the potential for future treatment, it appears to be an alternative option in these patients. It can postpone or avoid more mutilating surgery and self-catheterization.     

Can functional electric stimulation-assisted rowing reproduce a race-winning rowing stroke?

OBJECTIVE: To compare the ergometer rowing technique of a person with spinal cord injury (SCI), using functional electric stimulation (FES) of his leg muscles, with that of a well-defined group of able-bodied rowers. DESIGN: Whole-body kinematics and kinetics and electric activity of selected muscles were measured during ergometer rowing. SETTING: A hospital-based motion analysis laboratory. PARTICIPANTS: Five male university varsity-level rowers and 1 male rower with SCI. INTERVENTIONS: Eight rowing trials were collected on the university-level rowers, 2 trials each at 20, 24, 28, and 32 strokes/min. The rower with SCI had surface electrodes applied to his medial hamstrings and medial quadriceps muscle bellies. The electrodes were attached to a stimulator that was activated using a button in the ergometer handle. The subject with SCI rowed at a self-selected stroke rate. MAIN OUTCOME MEASURES: Forces at the ergometer handle and foot cradle, 3-dimensional whole-body kinematics, net joint moments, and phasic activity of muscles. RESULTS: Motion of the arms, ankles, and knees of the rower with SCI was similar to those of the university-level rowers; other joint motions and forces applied to the ergometer differed. CONCLUSIONS: FES-assisted rowing in its current implementation cannot reproduce a race-winning rowing stroke. Further development work is required.     

Pharmacological and behavioral properties of A-349821, a selective and potent human histamine H3 receptor antagonist

Histamine H3 receptors regulate the release of a variety of central neurotransmitters involved in cognitive processes. A-349821 ((4'-(3-((R,R)2,5-dimethyl-pyrrolidin-1-yl)-propoxy)-biphenyl-4-yl)-morpholin-4-yl-methanone) is a novel, non-imidazole H3 receptor ligand, displaying high affinity for recombinant rat and human H3 receptors, with pKi values of 9.4 and 8.8, respectively, and high selectivity for the H3 receptor versus H1, H2, and H4 histamine receptors. A-349821 is a potent H3 receptor antagonist in a variety of models using recombinant human and rat receptors, reversing agonist induced changes in cyclic AMP formation (pKb= 8.2 and pKb= 8.1, respectively), [35S]-GTPgammaS binding (pKb= 9.3 and pKb= 8.6, respectively) and calcium levels (human pKb= 8.3). In native systems, A-349821 competitively reversed agonist induced inhibition of electric field stimulated guinea-pig ileum (pA2= 9.5) and histamine-mediated inhibition of [3H]-histamine release from rat brain cortical synaptosomes (pKb= 9.2). Additionally, A-349821 inhibited constitutive GTPgammaS binding at both rat and human H3 receptors with respective pEC50 values of 9.1 and 8.6, demonstrating potent inverse agonist properties. In behavioral studies, A-349821 (0.4 mg/kg-4 mg/kg) potently blocked (R)-alpha-methylhistamine-induced dipsogenia in mice. The compound also enhanced cognitive activity in a five-trial inhibitory avoidance model in spontaneously hypertensive rat (SHR) pups at doses of 1-10mg/kg, with the 1mg/kg dose showing comparable efficacy to a fully efficacious dose of ciproxifan (3mg/kg). These doses of A-349821 were without effect on spontaneous locomotor activity. Thus, A-349821 is a novel, selective non-imidazole H3 antagonist/inverse agonist with balanced high potency across species and favorable cognition enhancing effects in rats.     

Repositioning of charged I-II loop amino acid residues within the electric field by beta subunit as a novel working hypothesis for the control of fast P/Q calcium channel inactivation

We have investigated the contribution of the Ca(v)beta subunits to the process of inactivation dependent of the I-II loop of Ca(v)alpha(2.1). Two amino acid residues located in the alpha1 interaction domain (AID) of the I-II loop of Ca(v)alpha(2.1) (Arg(387) and Glu(388)) have been directly implicated in voltage-dependent inactivation of this channel. Various point mutations of these residues disrupt the interaction between the I-II loop and the III-IV loop, and thereby modify the inactivation properties of the channel by accelerating its kinetics and shifting the steady-state inactivation curve towards hyperpolarized potentials. A similar disruption is produced by Ca(v)beta(4) subunit association with the I-II loop. Moreover, in the presence of Ca(v)beta(4) subunit, introducing negatively charged residues at positions 387 or 388 slows inactivation kinetics down, whereas introducing positive charges has the opposite effect. The shift of the steady-state inactivation curve is also amino acid charge-dependent. In contrast, mutation of Arg(387) or Glu(388) does not alter the differential regulation of the different Ca(v)beta isoforms on inactivation. These results suggest that the expression of Ca(v)beta(4) alters the contribution of charged residues at positions 387 and 388 to inactivation. We discuss these results with regard to the actual hypotheses on the mechanisms of calcium channel inactivation. We introduce the working concept that Ca(v)beta-subunits produce a conformational repositioning of charged AID residues within the electric field.     

The relationship between dorsal horn neurotransmitter content and allodynia in neuropathic rats treated with high-frequency transcutaneous electric nerve stimulation

Somers DL, Clemente FR. The relationship between dorsal horn neurotransmitter content and allodynia in neuropathic rats treated with high-frequency transcutaneous electric nerve stimulation. Arch Phys Med Rehabil 2003;84: 1575-83.Objective: To examine the relation between axon terminal neurotransmitter content in the dorsal horn and allodynia in neuropathic rats treated with high-frequency transcutaneous electric nerve stimulation (TENS).Design: A completely randomized experimental design. Two groups of rats received a chronic constriction injury to the right sciatic nerve, and 2 groups did not. The rats were either treated or not treated with TENS.Setting: Research laboratory.Animals: Adult male Sprague-Dawley rats (150-165g).Interventions: TENS was delivered daily for 1 hour to the chronic constriction injury rats or to the uninjured rats through self-adhesive electrodes applied to the skin innervated by the right dorsal rami of lumbar spinal nerves 1 to 6.Main Outcome Measures: Thermal and mechanical pain thresholds were assessed bilaterally in the hind paws of all rats twice before the chronic constriction injury surgery (baseline) and then 12 days after the surgery. An analogous time frame of assessment was used for rats that did not have chronic constriction injury surgery. Thermal and mechanical allodynia were expressed as difference scores between the pain thresholds of the right and left hind paws. These values were normalized to differences that existed between the 2 paws at baseline. The amino acid content of dorsal horn axon terminals was assessed bilaterally with high-pressure liquid chromatography, and values were normalized to wet weight.Results: The mean level of thermal and mechanical allodynia did not differ between the TENS-treated and untreated rats with chronic constriction injury. However, there was a significant relation between the dorsal horn, axon terminal content of glutamate (adjusted R²=.45, P<.01) and glycine (adjusted R²=.51, P<.005) and the magnitude of mechanical allodynia present in TENS-treated chronic constriction injury rats, but not in any other group. As axon terminal glutamate and glycine decreased in the right dorsal horn and increased in the left, mechanical allodynia was reduced or absent. When this trend was reversed, mechanical allodynia was more severe. Daily TENS also reduced the mean axon terminal content of aspartate, glutamate, and glycine bilaterally in the chronic constriction injury rats from the level observed in untreated neuropathic rats (P<.05).Conclusion: The variability in responsiveness of mechanical allodynia to daily TENS treatment in neuropathic rats is related to the axon terminal content of glutamate and glycine in the dorsal horn. These findings may help explain a similar variability in humans when TENS is used to treat neuropathic pain.