Imidazoline desensitization of epinephrine responses in rat vas deferens.

Repeated exposure of the rat vas deferens to the imidazoline oxymetazoline (OXY) results in a progressive loss of response which can appear selective for imidazoline agonists. The present study tests the hypothesis that imidazolines produce desensitization through prolonged blockade or inactivation of alpha-1 adrenoreceptors. Repeated exposure to OXY, naphazoline (NPZ) or tetrahydrozoline (THZ) produces a concentration- and time-dependent rightward shift and depression of the (-)-epinephrine concentration-effect curve, suggesting a mechanism of prolonged receptor blockade or inactivation. (-)-Epinephrine Kd values were similar when estimated after either receptor inactivation with phenoxybenzamine or repeated exposure to imidazolines. The differences in the ability of individual imidazolines to produce desensitization (order of potency: OXY greater than NPZ greater than or equal to THZ) do not follow their intrinsic activity (NPZ approximately THZ approximately OXY) or affinity (OXY greater than or equal to NPZ greater than THZ). The ability of individual imidazoline and phenethylamine agonists to produce a response in imidazoline-desensitized rat vas deferens reflects agonist intrinsic efficacy. Desensitization by imidazoline exposure does not affect contraction produced by either KCl or neurokinin A. Imidazolines produce effects similar to receptor inactivation and their desensitization in vas deferens can be explained without invoking an imidazoline subtype of alpha-1 adrenoreceptor.     

Reactive oxygen species mediate abnormal contractile response to sympathetic nerve stimulation and noradrenaline in the vas deferens of chronically diabetic rats: effects of in vivo treatment with antioxidants

Previous studies suggest that a link exists between increased oxidative stress and diabetic neuropathy. Moreover, antioxidants may protect neurones from the degenerative effects of reactive oxygen species. In our study, we used streptozotocin (STZ)-diabetic rats in a 8-month chronic diabetes model to study the effects of in vivo treatment with stobadine (ST), a pyridoindole antioxidant, and vitamin E. STZ-diabetic rats were treated with ST (24.7 mg/kg/day), vitamin E (D,L-alpha-tocopheryl acetate, 400-500 IU/kg/day) or ST plus vitamin E through an intra-oral catheter for a 8-month period beginning 10 days after STZ injection. Blood glucose and HbA1c levels were increased in diabetic rats by about 400 and 100%, respectively. Antioxidant treatment significantly decreased haemoglobin glycosylation (P < 0.05). We also determined the effects of chronic diabetes on sympathetic neurotransmission by measuring the contractility of isolated vas deferens. Furthermore, we investigated contractions elicited by electrical field stimulation (EFS) (1-64 Hz) which were significantly decreased in diabetic rats when compared with control rats. Treatment with ST or vitamin E alone partly enhanced the amplitude of the contractions induced by EFS, but a combination of ST and vitamin E treatment showed no additional effects. Contractile response of the vas deferens to exogenous noradrenaline, was increased in diabetic rats when compared with control rats. While the addition of vitamin E alone had no effect, ST completely returned noradrenaline-induced contractions to basal levels. The tension induced by 120 mm KCl was not statistically different among the experimental groups. In normal rats, EFS-induced contractions were significantly inhibited by pyrogallol (10(-4) m), a free-radical generator. Percentage inhibition of pyrogallol on EFS (32 Hz)-induced contractions in ring sections was 48 +/- 5.8 in control, 75 +/- 5.5 in untreated-diabetic, 54 +/- 2.7 in ST-treated diabetic, and 58 +/- 4.7 in vitamin E-treated diabetic rats. Combining both ST and vitamin E treatment had the same effects as each antioxidant alone with a percent inhibition of 48 +/- 6.8. These results are consistent with the degenerative changes seen in sympathetic nerves and the abnormal function observed in chronically diabetic rats, leading to a decrease in EFS response and an increase in response to adrenergic agonists in the vas deferens. Furthermore, we demonstrated that reactive oxygen species are responsible for impaired sympathetic neurotransmission and abnormal function of diabetic vas deferens, and that a combination of antioxidants may be better for the therapy of reproductive system disabilities in male diabetics.     

聚丙烯补片在腹股沟疝修补术中对输精管的影响

目的:探讨聚丙烯补片行腹股沟疝修补术对输精管的影响。方法:使用巴德公司生产SpomaTex补片进行疝修补,用来保护精索与输精管,并与同期单纯用聚丙烯平片行疝修补术的患者进行对比,观察二者对输精管的影响。结果:用SpomaTex补片与用普通补片行腹股沟疝修补的患者均未发现精索粘连及不育等并发症。结论:近期随访中,未发现精索粘连及不育等并发症,有待于长期各科合作的随访,国外已有聚丙烯补片引起不育的报道,应引起临床的高度重视。     

Differential effects of stimulus intensity on peripheral and neuromagnetic cortical responses to median nerve stimulation

To study the differential effects of tactile stimulus intensity on cortical and peripheral responses, we measured neuromagnetic cortical responses, compound muscle action potentials (CMAP), sensory nerve action potentials (SNAP), and the subjective estimation of tactile magnitude to electric median nerve stimulation at the wrist in 13 male healthy adults. The sensory perception threshold (ST) for electric pulses at wrist skin was determined and then various levels of stimulus intensity (1 approximately 6 ST) were given to each subject. At 1 ST, only the P50m components of the primary somatosensory (SI) cortical responses were recorded. The second somatosensory (SII) cortical responses were saturated at 2 ST, while the SI responses reached maximum at 3 ST equivalent to the subjective threshold intensity for "strong" tactility. The CMAP and SNAP were maximum at 4-5 ST. At 2 ST, >70% of maximum SI responses were produced, whereas only <40% of maximum CMAP or SNAP responses were obtained. We concluded that the stimulus intensities for activating or saturating somatosensory cortical responses were lower than those for CMAP and SNAP. The differential intensity effects on cortical and peripheral responses suggest a polysynaptic organization underlying the central amplification for somatosensory cortical activation. The optimal intensity levels for producing maximum SI and SII responses were 3 and 2 ST, respectively. Compared with the SII, the SI plays a crucial role in the coding of the tactile stimulus intensity.     

Selective blockade of angiotensin responses in the rabbit isolated vas deferens by angiotensin receptor antagonists

We examined the effect of two angiotensin receptor antagonists on neuromodulatory and prostaglandin-producing effects of angiotensin II in the rabbit isolated vas deferens because prior studies have established that angiotensins selectively influence the two neural events, one being adrenergic and the other nonadrenergic. Angiotensin II increased adrenergic neurotransmission and prostaglandin E synthesis in a concentration-dependent manner while depressing nonadrenergic neurotransmission. The [1-Sarcosine, 8-Alanine]-angiotensin II preferentially antagonized adrenergic neuromodulatory effects of angiotensin II. In contrast, the nonadrenergic neuromodulatory and prostaglandin E-releasing effects of angiotensin II were suppressed by [1-Sarcosine, 8-Alanine]-angiotensin II to a lesser extent. The nonpeptide angiotensin receptor antagonist, Dupont 753 (2-n-butyl-4-chloro-5-hydroxymethyl-1-[2(1)-(1-H-tetrazol-5-yl) biphenyl-4-yl)methyl] imidazole, potassium salt, exhibited the opposite selectivity. It eliminated the depression of nonadrenergic neurotransmission without significantly altering the potentiation of adrenergic neurotransmission caused by angiotensin II. The angiotensin-induced stimulation of prostaglandin E synthesis was also eliminated by this antagonist. These data suggest that angiotensin effects in the vas deferens are mediated by at least two types of angiotensin receptors.     

The effects of transcutaneous electrical nerve stimulation on spasticity

Abstract

Transcutaneous electrical nerve stimulation (TENS) is commonly used in the treatment of chronic and acute pain with possible mechanisms of action including segmental inhibition, release of endogenous opioids, counter-irritation, nerve conduction block, and placebo. Although not frequently used in current practice, there is some evidence that TENS has an effect on spasticity in neurological conditions such as stroke, spinal cord injury, and multiple sclerosis. This paper reviews the results of studies undertaken to date, evaluating not only the effects of TENS on spasticity, but also the impact of different TENS parameters on its overall effectiveness. Recommendations based on the current evidence for the use of TENS in the treatment of spasticity are made, as well as suggestions for further study.     

Adenosine receptor antagonism attenuates angiotensin II effects on adrenergic neurotransmission in the rabbit isolated vas deferens

Angiotensin II augments adrenergic neurotransmission in the rabbit isolated vas deferens and suppresses purinergic neurotransmission. This study tests the hypothesis that angiotensin II augments adrenergic neurotransmission by depressing the neuronal release of ATP, resulting in suppressed formation of the inhibitory neuromodulator, adenosine or a related purine. Exogenous ATP added to the vasa deferentia increased adenosine formation and depressed adrenergic neurotransmission thus providing indirect support for the hypothesis. The adenosine receptor antagonist, 8-(sulfophenyl)theophylline (10 and 100 microM) depressed responses to exogenous adenosine and ATP but did not alter contractile responses to nerve stimulation or exogenously administered norepinephrine thus indicating that endogenous adenosine had no basal influence upon neurotransmission. However, the 8-(sulfophenyl)theophylline reduced angiotensin II effects on both adrenergic neurogenic contractions and evoked norepinephrine release. Additionally, the augmentation of adrenergic neurogenic contractions by angiotensin II was enhanced in the presence of ATP. These results are consistent with an ATP involvement in angiotensin effects on adrenergic neurotransmission and contrary to the initial hypothesis, suggest that purines enhance adrenergic neurotransmission in the presence of angiotensin II.     

Mode of the ciguatoxin-induced supersensitivity in the guinea-pig vas deferens

Ciguatoxin (CTX; 10(-7) X 10(-7) g/ml), the most potent marine toxin isolated from a number of tropical and subtropical fishes, shifted the dose-contractile response curves for norepinephrine (NE) and K+ to the left in a parallel manner in the guinea-pig isolated vas deferens, indicating that CTX caused supersensitivity. The CTX-induced potentiation was inhibited or abolished in the presence of tetrodotoxin (5 X 10(-7) M) or saxitoxin (5 X 10(-7) M) and in Na+-deficient medium, but was not affected by phentolamine (10(-6) M) and verapamil (10(-6) M). Treatment with reserpine (2 mg/kg/day, twice) almost completely prevented the release of NE by CTS, such pretreatment had no affect on the ability of CTX to potentiate responses to NE and K+. Furthermore, after cold storage (4 degrees C for 7 days) of tissues, the contractile response to NE (3 X 10(-6) M) and K+ (20 mM) was still profoundly potentiated after treatment with CTX (5 X 10(-7) g/ml). CTX (10(-7)-10(-5) g/ml) by itself had no apparent effect on either Na+, K+-adenosine triphosphatase activity or Na+ content of the vas deferens. However, in the presence of ouabain, CTX elevated the Na content of the vas deferens treated with ouabain alone by 27%. This effect of CTX was abolished by tetrodotoxin. These data suggest that CTX causes an increasing Na+ permeability across the TTX sensitive Na+ channels of smooth muscle cell, and this may play an important role in its mechanism of potentiation.     

The effects of transcutaneous electrical nerve stimulation on post-cesarean pain

The purpose of this study was to examine the effect of continuous transcutaneous electrical nerve stimulation (TENS) near the incision site on post-cesarean pain and on analgesic intake during the early postoperative period. This investigation utilised a 2-group (TENS-treated and placebo TENS-treated), single-blind experimental design. Eighteen multiparous women, each having undergone an elective cesarean delivery, participated in the study. Nine patients received TENS and nine placebo stimulation. The treatment was continuous through to the third day following the day of surgery. The McGill Pain Questionnaire was used to estimate the three most frequent types of post-cesarean-associated pain, and records of the patients' analgesic intake were obtained from hospital charts. The results suggest that TENS was significantly more effective than placebo TENS in reducing cutaneous, movement-associated incisional pain. However, pain resulting from internal structures, i.e., deep pain, afterbirth pain (due to uterine contractions), and the somatic pain associated with decreased peristalsis (gas pains) were not amenable to TENS. No significant differences in analgesic intake were observed. The possible reasons for these findings are discussed.     

Calcification of vas deferens associated with diabetes mellitus

Calcification of the vas deferens may be associated with diabetes mellitus. This paper discusses the case of a patient in which this occurred. In clinical practice, this radiological finding may indicate further diagnostic workup for diabetes or other causative conditions which are described here.