Regional renal and splanchnic blood flows during nicotine infusion: effects of alpha and of combined alpha and beta adrenergic blockade

Renal (cortex and medulla) and splanchnic (duodenum, liver, pancreas and spleen) blood flows were measured with 25-mu radioactive microspheres in anesthetized, open-chest dogs. The effects of nicotine (36 micrograms/kg/min i.v.) before and after selective alpha adrenergic blockade (phenoxybenzamine, 1 mg/kg i.v.) and before and after combined alpha and beta adrenergic blockade (phenoxybenzamine, 1 mg/kg i.v. and propranolol, 1 mg/kg i.v.) were evaluated. Before adrenergic blockade, nicotine increased arterial pressure (+82%) but had heterogeneous directional effects on regional blood flows: pancreas (-64%), duodenum (-33%), kidney cortex (-31%), kidney medulla (-17%), liver (+5%) and spleen (+71%). Vascular conductance was reduced in kidney cortex (-61%), kidney medulla (-57%), duodenum (-59%), liver (-46%) and pancreas (-79%) and was not altered in spleen. Selective alpha adrenergic blockade prevented the hypertensive response to nicotine, but heterogeneous changes in regional flows persisted: pancreas (-40%), spleen (-40%), kidney medulla (-35%), kidney cortex (-31%), liver (+50%) and duodenum (+74%). After combined alpha and beta adrenergic blockade, nicotine increased systemic arterial pressure (+75%) and decreased vascular conductance in all tissues. Results indicate: 1) a heterogeneous influence of nicotine in renal and splanchnic circulations associated with regional differences in activities of alpha and beta adrenergic receptors and 2) a potent nonadrenergic vasoconstrictor response in these circulations to nicotine after blockade of alpha and beta adrenergic receptors.     

自主平衡恢复过程中姿势调控反应时与运动时的增龄性变化研究

摘要目的：观察人体在失稳后的自主平衡恢复过程中姿势调控反应时间与运动时间的增龄趋势与年龄敏感性变化区。方法：使用DE-A体感平衡检测系统对20—79岁的健康成年受试者97例进行姿势调控时间测试,包括在静态平衡与动态平衡状态下的支撑面前倾、后倾、左倾和右倾失稳应激时的姿势调控反应时与运动时测试,并记录所有测试的各姿势调控时间指标。按照10岁为一年龄分段将受试者依次分为6个年龄组,其中组1（20—29岁）为16例、组2（30—39岁）为10例、组3（40—49岁）为17例、组4（50—59岁）为18例、组5（60—69岁）为31例、组6（70—79岁）为5例,观察姿势调控反应时与运动时的增龄变化,并分析其年龄敏感变化区。结果：姿势调控反应时和运动时随年龄增长呈现延长趋势。静态平衡状态下,组6的各反应时和运动时均较组1—5长,与组1—4比较均具有显著性差异（P＜0.05）,与组5比较均无显著性差异（P＞0.05）;组5的各反应时和运动时均较组1—4长,且均具有显著性差异（P＜0.05）;组4的各反应时和运动时均较组1—3长,支撑面右倾时的反应时与组1比较具有显著性差异（P＜0.05）,其余指标组间比较均无显著性差异（P＞0.05）;组3的各反应时和运动时均较组1—2长,支撑面左倾时的运动时与组1比较具有显著性差异（P＜0.05）,其余指标组间比较均无显著性差异（P＞0.05）;组2的各反应时和运动时与组1比较均无显著性差异（P＞0.05）。动态平衡状态下,组6的各反应时和运动时均较组1—5长,与组1—4比较均具有显著性差异（P＜0.05）,与组5比较均无显著性差异（P＞0.05）;组5的各反应时和运动时均较组1—4长,且均具有显著性差异（P＜0.05）;组4的各反应时和运动时均较组1—3长,支撑面左倾时的反应时与组1比较无显著性差异（P＞0.05）,其余指标组间比较均具有显著性差异（P＜0.05）,而支撑面后倾和左倾的运动时与组2比较具有显著性差异（P＜0.05）,其余指标组间比较均无显著性差异（P＞0.05）;组3的各反应时和运动时均较组1—2长,各运动时与组1比较均具有显著性差异（P＜0.05）,而各反应时与组1比较无显著性差异（P＞0.05）;组2的各反应时和运动时与组1比较均无显著性差异（P＞0.05）。结论：人体在失稳后的自主平衡恢复过程中姿势调控反应时和运动时随年龄增长而逐渐延长。静态平衡恢复的姿势调控反应时和运动时可能在60岁左右开始出现明显恶化,而动态平衡恢复的姿势调控反应时与运动时可能分别在50岁左右和40岁左右便开始出现明显恶化。     

Haemodynamic effects of low and high doses of insulin during beta receptor blockade in dogs

Summary. Haemodynamic effects of small and high doses of insulin during beta receptor blockade were studied in nine dogs. Beta receptor blockade was induced by 0.5 mg/kg propranolol and caused depression of cardiac performance with a significant increase in left ventricular end-diastolic pressure (LVEDP) and a significant decrease in heart rate; maximum rate of left ventricular (LV) pressure rise (LVdP/dt_max), stroke volume and cardiac output. At 15 min, after beta receptor blockade, a bolus injection of 0.5 IU/kg of insulin, free of glucagon and calcium, was given followed by a continuous infusion of 0.5 IU/kg/h. After 30 min another bolus dose of 300 IU insulin was injected. Glucose and potassium were given to maintain physiological levels of these factors. Five minutes after a low dose of insulin there was a significant decrease in LVEDP (P<0.01), and a significant increase in LVdP/dt_max (P<0.01), in stroke volume (P<0.01) and in cardiac output (P<0.01). The other haemodynamic variables were not significantly changed. Administration of a high dose of insulin further, significantly, improved performance of the beta receptor blocked heart and caused a significant reduction in total peripheral resistance. In conclusion, insulin exerts inotropic and vasodilator effects which are dose-dependent and not related to adrenergic mechanisms.     

Increased pain sensitivity in fibromyalgia: effects of stimulus type and mode of presentation

Fibromyalgia (FM) is defined in part by sensitivity to blunt pressure. Pressure pain sensitivity in FM is evaluated typically by the use of 'ascending' testing methods such as tender point counts or dolorimetry, which can be influenced by response bias of both the subject and examiner. Methods that present stimuli in a random, unpredictable fashion might minimize the influence of these factors. In this study, we compared the results of ascending and random assessments of both pressure and thermal pain sensitivities in 43 FM patients and 28 age- and gender-matched controls. Even though FM is defined on the basis of pressure sensitivity, this group was also more sensitive to heat stimuli, presented in either ascending or random paradigms. In both the patient and control groups, the pain ratings to painful sensations evoked by both thermal and pressure stimuli were significantly greater in the random, compared with the ascending method. The number of subjects classified as 'expectant' because they rated pain higher in ascending than random paradigms was similar for FM and control groups. Both patients and controls exhibited a similar degree of sensitization to pressure and thermal stimuli. The increased sensitivity to both pressure and thermal stimuli for threshold and suprathreshold stimuli in FM patients is consistent with central augmentation of pain processing.     

Alterations in cardiac alpha and beta adrenoceptors during the development of spontaneous hypertension

To study potential cardiac receptor alterations during the development of spontaneous hypertension, specific binding of [3H]-2-N(2,6-dimethoxyphenoxyethyl)amino-methyl-1,4-benzodioxane, (-)-[3H]dihydroalprenolol and (-)-[3H]quinuclidinyl benzilate in ventricles of Wistar Kyoto rats (WKY), spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) at different ages was determined. The Kd and maximal binding for specific binding of [3H]-2-N(2,6-dimethoxyphenoxyethyl)amino-methyl-1,4-benzodioxane and (-)-[3H]dihydroalprenolol in ventricular homogenates of SHR and SHRSP at prehypertensive ages were similar to those of age-matched WKY. With the development of spontaneous hypertension in SHR and SHRSP, there was a significant decrease in the maximal binding for both ligands without a change in Kd. The decrease in maximal binding in SHR and SHRSP at 10 weeks of age was 29 to 38%, compared with age-matched WKY. There was no difference in ventricular (-)-[3H]quinuclidinyl benzilate binding between WKY and SHRSP. Hofstee analysis of the inhibition of ventricular (-)-[3H]dihydroalprenolol binding by practolol demonstrated a specific 51% decrease in ventricular beta-1 receptor density in 10-week-old SHRSP. In addition, the inotropic response to isoproterenol in isolated papillary muscles from SHRSP was significantly smaller than that in WKY. Thus, it is concluded that during the development of spontaneous hypertension in SHR and SHRSP, there is a specific loss in number of cardiac alpha and beta-1 adrenoceptors with a consequently reduced responsiveness of isolated papillary muscles to isoproterenol in SHRSP. These results are compatible with the reported increase in sympathetic outflow to the cardiovascular system in spontaneous hypertension.     

Relative importance of alpha and beta adrenergic receptors during resuscitation.

Successful resuscitation from cardiac arrest in the asphyxiated dog model has been ascribed to the use of artificial ventilation, closed chest cardiac massage, and administration of a vasopressor. Controversy remains over whether the most commonly employed vasopressor, epinephrine, exerts its effects primarily by elevating diastolic pressure and reestablishing coronary flow, or by exciting cardiac pacemaker cells and enhancing myocardial contractility. To observe pure alpha and beta adrenergic receptor influences during resuscitation, three groups (alpha-blocked, beta-blocked, unblocked) of dogs were studied. beta-blocked dogs resuscitated with phenylephrine and unblocked dogs resuscitated with epinephrine experienced 100% successful resumption of spontaneous circulation after 5 min of asphyxia-induced arrest. Only 27% of alpha-blocked animals resuscitated with isoproterenol were successfully revived. The appearance of the ECG during cardiac arrest and resuscitation could in no way be used to predict the outcome of resuscitation attempts. Results suggest that, initially, alpha receptor stimulation with concomitant diastolic pressure elevation is more important to the success of resuscitation than beta receptor stimulation.     

Modulated activation of the human SI and SII cortices during observation of hand actions

Neurons in area F5 of the monkey premotor cortex are activated during both execution and observation of hand actions. A similar "mirror-neuron system" seems to exist also in the human brain, including at least the superior temporal sulcus region, Broca's area, and the primary motor cortex. We recorded somatosensory evoked fields in response to median nerve stimulation from nine healthy subjects during (i) rest, (ii) manipulation of a small object, and (iii) observation of the same action to find out to what extent the somatosensory cortices display behavior similar to the human mirror-neuron system. SI signals were enhanced and SII signals suppressed during both manipulation and observation, except when the right manipulating hand was stimulated. Our results suggest that the SI and SII cortices contribute to the human mirror-neuron system, possibly providing information necessary for preserving the sense of self during action observation.     

Contribution of alpha 1GABAA and alpha 5GABAA receptor subtypes to the discriminative stimulus effects of ethanol in squirrel monkeys

Ethanol's ability to enhance GABA neurotransmission via GABA(A) receptors has been implicated as an important mechanism underlying its discriminative stimulus (DS) effects in animals and subjective effects in humans. The present study assessed the contribution of alpha(1)GABA(A) and alpha(5)GABA(A) receptors to the DS effects of ethanol. Squirrel were monkeys trained to discriminate i.v. ethanol from saline under a fixed-ratio schedule of food delivery. Under test conditions, ethanol engendered a dose-dependent increase in drug-lever responding, reaching an average maximum of >80%. In substitution experiments, the alpha(1)GABA(A) agonists zolpidem, zaleplon, and CL 218,872 (3-methyl-6-[3-(trifluoromethyl)phenyl]-1,2,4-triazolo[4,3-b]pyridazine), the alpha(5)GABA(A) agonists QH-ii-066 (1-methyl-7-acetyleno-5-phenyl-1,3-dihydro-benzo[e]-1,4-diazepin-2-one) and panadiplon [3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-5-(1-methylethyl)imidazo(1,5-a)quinoxalin-4(5H)-one], and representative nonselective agonists partially to fully reproduced the ethanol DS. In antagonism studies, the alpha(1)GABA(A) antagonist beta-carboline-t-butyl ester did not attenuate the DS effects of ethanol or the ethanol-like effects of zolpidem and zaleplon. In contrast, pretreatment with the alpha(5)GABA(A) inverse agonist L-655,708 (ethyl[S]-11,12,13,13a-tetrahydro-7-methoxy-9-oxo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxlate) dose-dependently attenuated the DS effects of ethanol and the ethanol-like effects of QH-ii-066. RY-23 (tert-butyl 8-[(trimethylsilyl)ethynyl]-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5a]-[1,4]benzodiazepine-3-carboxylate), another alpha(5)GABA(A) inverse agonist, similarly attenuated the ethanol-like DS effects of QH-ii-066. Antagonism of both QH-ii-066 and ethanol by the alpha(5)GABA(A) inverse agonists occurred at doses that did not alter the rate of responding suggesting that this blockade was pharmacologically specific and not the result of a nonspecific disruption of operant behavior. These findings suggest a key role for alpha(5)GABA(A), but not alpha(1)GABA(A), receptor mechanisms in the DS effects of ethanol and the ethanol-like DS effects of benzodiazepine agonists.     

Radiofungicidal effects of external gamma radiation and antibody-targeted beta and alpha radiation on Cryptococcus neoformans

We evaluated the clonogenic survival, membrane permeability, metabolic activity (XTT reduction), and apoptosis (FLICA binding) of Cryptococcus neoformans cells subjected to gamma rays from an external source, and beta and alpha particles delivered to fungal cells by capsule-specific antibody. We found that gamma, beta, and alpha radiation affected cells through different pathways.     

Gallstone movement during lithotripsy: mechanisms and effects on fragmentation.

We sought to examine the mechanisms of gallstone movement and its effect on gallstone fragmentation in vitro. Two experiments were performed in four specially constructed phantoms that allowed decreasing degrees of movement during the application of shock waves. Shock waves caused displacement of the stone from the focus, but the stone and its fragments were returned to the focus by streaming movements in the coupling liquid when the volume of surrounding fluid was small. Streaming movements were ineffective in large volumes. Restraining movements of the gallstone did not improve the results of fragmentation. We conclude that radiation force and the streaming motion of the surrounding liquid account for movements of the stone and fragments during lithotripsy. Lithotripsy is more effective when smaller volumes are used because streaming brings fragments back to the focus of the lithotripter. Total immobilization of the stone in the focus of the lithotripter, however, offers no benefit, probably because it inhibits rotational movement of the stone.     

Differential effects of zeta and eta transgenes on early alpha/beta T cell development

The zeta-family dimers (zeta, eta, and gamma) are a group of structurally and functionally related proteins that are expressed in developing thymocytes and function as signal transducing subunits of the T cell antigen receptor (TCR) and certain Ig Fc receptors. Zeta, eta, and gamma each contain one or more copies of a conserved tyrosine- based activation motif (TAM) that is known to be required for signal transduction. To examine the developmental importance of multiple or individual TAM elements we generated transgenic mice that express: (a) full-length (FL) zeta-chain (3 TAMs); (b) eta-chain, a naturally occurring variant of zeta that is derived from alternative splicing (2 TAMs); or (c) truncated zeta-chain (CT108; 1 TAM), under the control of the human CD2 promoter and regulatory elements. Unexpectedly, we found that overexpression of the FL zeta chain caused premature termination of RAG-1 and RAG-2 expression, prevented productive rearrangement of the TCR-alpha and TCR-beta genes and blocked entry of thymocytes into the CD4/CD8 developmental pathway. In contrast, we found that overexpression of eta or CT108 had no effect on normal thymocyte maturation. These results suggest that an early signaling pathway exists in precursor TCR- thymocytes that can regulate RAG-1 and RAG-2 expression and is differentially responsive to individual members of the zeta-family dimers.     

Qualitative differences in the discriminative stimulus effects of low and high doses of caffeine in the rat

Caffeine engenders qualitatively different subjective effects in humans at low and high doses. Low doses of caffeine are mildly reinforcing and produce psychomotor stimulation. High doses of caffeine can produce subjective feelings of anxiety, dysphoria and depression. The present study was designed to model these different subjective states in rats using a discrete trial shock avoidance/escape drug discrimination paradigm. Rats were trained to discriminate between i.p. injections of saline and either 10 or 56 mg/kg of caffeine. Rats trained at 10 mg/kg of caffeine acquired the discrimination in an average of 93 sessions and generalized completely to a variety of xanthine and nonxanthine behavioral stimulants including: d-amphetamine, apomorphine, 7-(beta-chloroethyl)theophylline, 9-chloro-2-(2-furanyl)-5,6-dihydro-1, 2,4-triazolo[1,5-c]quinazolin-5-imine (CGS 15943), cocaine, 1,7-dimethylxanthine, diethylpropion, beta-hydroxyethyltheophylline, methylphenidate, phenidimetrazine and theophylline. Rats trained at 56 mg/kg of caffeine acquired the discrimination in an average of 43 sessions and generalized completely only to theophylline. A variety of drugs representing diverse pharmacologic classifications including: benzodiazepine inverse agonists, pentylenetetrazol, yohimbine, ethylketocyclazocine and phencyclidine, were not generalized from either training dose, demonstrating the pharmacologic specificity of the discrimination. The discriminative effects of 10 mg/kg of caffeine appear to derive from a state of behavioral arousal, possibly mediated by catecholamines, and parallel the subjective effects produced by low doses of caffeine in humans. The discriminative effects of 56 mg/kg of caffeine are qualitatively different from those of 10 mg/kg but cannot be defined further at this time.     

A small molecule alpha4beta1/alpha4beta7 antagonist differentiates between the low-affinity states of alpha4beta1 and alpha4beta7: characterization of divalent cation dependence

An alpha4beta1/alpha4beta7 dual antagonist, 35S-compound 1, was used as a model ligand to study the effect of divalent cations on the activation state and ligand binding properties of alpha4 integrins. In the presence of 1 mM each Ca2+/Mg2+, 35S-compound 1 bound to several cell lines expressing both alpha4beta1 and alpha4beta7, but 2S-[(1-benzenesulfonyl-pyrrolidine-2S-carbonyl)-amino]-4-[4-methyl-2S-(methyl-[2-[4-(3-o-tolyl-ureido)-phenyl]-acetyl]-amino) pentanoylamino]-butyric acid (BIO7662), a specific alpha4beta1 antagonist, completely inhibited 35S-compound 1 binding, suggesting that alpha4beta1 was responsible for the observed binding. 35S-Compound 1 bound RPMI-8866 cells expressing predominantly alpha4beta7 with a KD of 1.9 nM in the presence of 1 mM Mn2+, and binding was inhibited only 29% by BIO7662, suggesting that the probe is a potent antagonist of activated alpha4beta7. With Ca2+/Mg2+, 35S-compound 1 bound Jurkat cells expressing primarily alpha4beta1 with a KD of 18 nM. In contrast, the binding of 35S-compound 1 to Mn2+-activated Jurkat cells occurred slowly, reaching equilibrium by 60 min, and failed to dissociate within another 60 min. The ability of four alpha4beta1/alpha4beta7 antagonists to block binding of activated alpha4beta1 or alpha4beta7 to vascular cell adhesion molecule-1 or mucosal addressin cell adhesion molecule-1, respectively, or to 35S-compound 1 was measured, and a similar rank order of potency was observed for native ligand and probe. Inhibition of 35S-compound 1 binding to alpha4beta1 in Ca2+/Mg2+ was used to identify nonselective antagonists among these four. These studies demonstrate that alpha4beta1 and alpha4beta7 have distinct binding properties for the same ligand, and binding parameters are dependent on the state of integrin activation in response to different divalent cations.     

Agonist and antagonist effects of interferon alpha and beta on activation of human macrophages. Two classes of interferon gamma receptors and blockade of the high-affinity sites by interferon alpha or beta

H2O2-releasing capacity and limited antitoxoplasma activity could be induced in human macrophages (derived from monocytes cultured greater than or equal to 5 d) but not in monocytes themselves (cells cultured less than or equal to 4 d) by a further 3-d incubation with pure natural or rIFN-alpha or -beta. More than 3 pM (10 U/ml) of these IFNs was required, with greatest effects at approximately 300 pM (10(3) U/ml). At 300 pM, H2O2-releasing capacity was enhanced 4.4 +/- 1.6-fold over medium control (mean +/- SD for natural INF-alpha, rIFN-alpha A, rIFN-alpha D, and rIFN-beta) compared to an 8.4 +/- 4.8-fold increase with rIFN-gamma (100 pM, 100 U/ml) in the same experiments. Unexpectedly, low concentrations of IFN-alpha or -beta (3 fM-300 pM) blocked induction of H2O2-releasing capacity by rIFN-gamma (10 pM), with a 50% inhibitory dose of approximately 80 fM. However, IFN-alpha or -beta (3 fM-300 pM) could not inhibit the effect of higher concentrations of rIFN-gamma (1 nM). In contrast to results with monocytes or young macrophages, Scatchard plots of binding of 125I-rIFN-gamma to mature macrophages (day 8 of culture) indicated two classes of binding sites: approximately 2,000 high-affinity sites (Kd approximately 0.43 nM) and approximately 23,000 low-affinity sites (Kd approximately 6.4 nM) per cell. Binding of 125I-rIFN-gamma to the high- but not the low-affinity sites was blocked by simultaneously added IFN-alpha or -beta, with a 50% inhibitory dose of approximately 2 U/0.25 ml (approximately 2 pM), or reversed by subsequently added IFN-alpha or -beta. Thus, differentiation of human mononuclear phagocytes in vitro is accompanied by the emergence of (a) an agonist response to submicromolar concentrations of IFN-alpha or -beta, (b) antagonism of the effect of picomolar IFN-gamma by femtomolar IFN-alpha or -beta, (c) two classes of IFN-gamma-Rs, and (d) nonstimulatory binding of IFN-alpha or -beta to the high- but not the low-affinity IFN-gamma-Rs, with higher affinity than rIFN-gamma itself. We speculate that traces of IFN-alpha or -beta derived from stromal cells, parenchymal cells, or resident macrophages may dampen the activation of mature tissue macrophages by the small amounts of IFN-gamma that diffuse from inflammatory sites into normal tissues. Such a mechanism could constrain the potentially destructive phenomenon of macrophage activation to areas where monocytes have recently immigrated and/or the concentration of IFNs is high.     

Effect of aromatic fluorine substitution on the alpha and beta adrenoceptor-mediated effects of 3,4-dihydroxytolazoline in the pithed rat

The alpha and beta adrenoceptor-mediated effects of the catecholimidazoline, 3,4-dihydroxytolazoline, and its 2-, 5- and 6-aromatic fluorine-substituted derivatives have been studied in the cardiovascular system of the pithed rat. All four compounds produced vasopressor responses in beta adrenoceptor blocked (propranolol, 3 mg/kg i.v.) animals. The pressor responses produced by all four compounds were antagonized by the selective alpha-1 adrenoceptor antagonist, prazosin (0.1 mg/kg i.v.), and were relatively unaffected by the selective alpha-2 adrenoceptor antagonist, rauwolscine (0.5 mg/kg i.v.), indicating that vasoconstriction produced by the fluorinated imidazolines was mediated exclusively by postjunctional vascular alpha-1 adrenoceptors. The rank order of potency at the alpha-1 adrenoceptor was: 5-fluoro greater than 2-fluoro greater than desfluoro greater than 6-fluoro. At higher doses, 3,4-dihydroxytolazoline and its fluorinated derivatives produced an alpha-2 adrenoceptor-mediated inhibition of neurogenic tachycardia in animals pretreated with prazosin, with all four compounds being equipotent. In rats with complete alpha adrenoceptor blockade [phenoxybenzamine (3 mg/kg i.v.), prazosin (0.1 mg/kg i.v.) and rauwolscine (1 mg/kg i.v.)] whose blood pressure was elevated by constant infusion of angiotensin II (150 ng/kg/min i.v.), high doses of the 2-fluoro-, but not the 5-, 6- or desfluoro catecholimidazoline derivatives, produced a beta-2 adrenoceptor-mediated vasodepressor response. All four compounds produced a beta-1 adrenoceptor-mediated positive chronotropic response in pithed rats with the rank order of potency being: 2-fluoro = 5-fluoro greater than desfluoro greater than 6-fluoro.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiac responsiveness to alpha and beta adrenergic amines: effects of carbachol and hypothyroidism

Previous reports of cardiac beta to alpha adrenoceptor interconversion secondary to hypothyroidism left open the alternative possibility of a functional influence by hypothyroidism on the inotropic and chronotropic effects of adrenergic amines through a different mechanism. To test this possibility, the effects of hypothyroidism (thyroidectomy) were compared with those of acute carbachol pretreatment on the responses of isolated rat atria to the selective beta and alpha adrenoceptor agonists isoproterenol and methoxamine. Both hypothyroidism and acute carbachol pretreatment (3 X 10(-7) -10(-6) M): 1) reduced basal right atrial rates and left atrial tensions; 2) caused an apparent decrease in the inotropic and chronotropic potencies of isoproterenol; 3) reduced the degree of antagonism by propranolol of the responses to isoproterenol; 4) increased the maximum inotropic response of left atria to methoxamine; and 5) converted a lack of response to a positive chronotropic response of right atria to methoxamine. Equivalent reductions of basal rates by hypothermia, or of basal tensions by lowered calcium ion concentrations, did not affect the responses to isoproterenol or methoxamine. The results suggest that both carbachol pretreatment and hypothyroidism functionally antagonize the responses to isoproterenol and enhance the responses to methoxamine by means other than adrenoceptor interconversion.     

运动状态下索他洛尔对男女心室复极影响的性别差异

目的　探讨在运动状态下索他洛尔对心室复极作用的性别差异。方法　研究以随机、双盲、安慰剂、自身对照为原则 ,对 31例男性和 30例女性健康志愿者 ,通过活动平板运动试验 ,分别观察口服索他洛尔后静息时和运动时男女之间体表心电图上反映心室复极过程的QTc和JTc间期的不同变化 ,并用安慰剂做对照。结果　口服索他洛尔后 ,静息时女性的JTc间期显著长于男性 ,分别为 :(2 71 0 5± 18 0 9)ms比 (2 2 9 75± 15 5 9)ms ,P <0 0 0 1;男、女运动高峰时JTc缩短的百分率 :服索他洛尔时为 3 6 4 %±4 93%比 13 2 6 %± 6 0 9% ,P <0 0 1;此时男、女JTc间期的差异消失 ,分别为 :(2 2 0 17± 13 0 4 )ms比(2 19 4 8± 10 85 )ms,P >0 0 5。结论　口服索他洛尔后 ,虽然静息时女性的心室复极时间明显长于男性 ,但运动中女性心室复极时间的缩短比男性显著 ,这种性别之间的差异比口服安慰剂时更明显     

Analysis of terrain effects on the interfacial force distribution at the hand and forearm during crutch gait

Forces transferred to the upper body during crutch use can lead to both short-term and long-term injuries, including joint pain, crutch palsy, and over-use injuries. While this force transmission has been studied in controlled laboratory settings, it is unclear how these forces are affected by irregular terrains commonly encountered during community ambulation. The purpose of this study was to determine the effects of walking speed and uneven terrain on the load magnitude, distribution, and rate of loading at the human-crutch contact surfaces. Our results show that the rates of loading were significantly increased with higher walking speeds and while negotiating certain irregular terrains, despite there being no apparent effect on the peak force transmission, suggesting load rate may be a more appropriate metric for assessing terrain effects on crutch gait. Furthermore, irrespective of the type of terrain and walking condition, the largest compressive forces were found to reside in the carpal-tunnel region of the hand, and may therefore be a primary contributor to carpal-tunnel injury.