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Biomedical subjects

E R Smith

Publications and source records attributed to E R Smith.

At least 217 records · Page 12Linked to original sources

Effects of vasoactive intestinal peptide on canine prostatic contraction and secretion.

Vasoactive intestinal peptide (VIP)-like immunoreactivity was found in intrinsic autonomic ganglion cells and nerve fibers located at the surface and within the canine prostate. In anesthetized dogs, porcine VIP (100-3,000 ng/kg iv) decreased arterial pressure and increased heart rate but did not result in the release of fluid from the prostate, indicating that VIP neither contracted glandular smooth muscle to expel fluid nor provoked secretion. Intravenous infusions of VIP at 10, 50, 100, and/or 200 ng X kg-1 X min-1 produced dose-related decreases in arterial pressure, increases in heart rate, and potentiation of the secretory response to the intravenous administration of pilocarpine and to electrical stimulation of the hypogastric nerves at 2 but not at 20 Hz. VIP at 1 microgram/ml neither contracted isolated strips of prostate nor modified their contraction by norepinephrine. It is unlikely that VIP mediates hypogastric nerve-induced prostatic contraction or secretion in the dog, but VIP may serve as a neuromodulator of nerve-induced secretion.

Animals↗

Maintenance of sexual function in a castrated man treated with ovarian steroids.

Sexual function, mood states, and endocrine levels were studied in a 48-year-old man who had been castrated bilaterally because of severe post-vasectomy orchialgia and who habitually uses oral estrogen and progestin. He reported satisfactory sexual behavior with a usual coital frequency of at least twice per week while on treatment with Premarin and Provera. Though his nocturnal penile tumescence (recorded on a portable home monitor) was very low while on this treatment, psychophysiological tests showed that erectile responses to erotic film were well within the normal range for control subjects in this laboratory. A double-blind experiment was performed to assess his sexual functioning and mood states during treatment with placebo, testosterone enanthate, and estradiol valerate, with and without progesterone (one injection of each, with 4-week intervals between treatments). All treatments generated prolonged changes in circulating hormone levels; testosterone treatment was associated with elevated estradiol levels, and estradiol with massively increased plasma prolactin. Coital frequency was highest with the estrogen-progestin treatment and lowest with placebo. Testosterone precipitated a very high frequency of spontaneous erections and severe negative affect. The subject also reported low sexual drive and poor mood states while taking Provera alone. It was concluded that the preferred estrogen-progestin treatment of this patient, probably in conjunction with minimal androgen levels from his adrenal, are most likely responsible for maintaining his satisfactory sexual functioning. There is no evidence that other castrates would necessarily benefit from a similar hormonal regimen.

Castration↗

Penile reflexes in intact rats following anesthetization of the penis and ejaculation.

Application of the topical anesthetic pontocaine (tetracaine hydrochloride) to the penis and preputial sheath virtually abolished the display of penile reflexes by intact rats. When pontocaine was applied immediately following ejaculation in copula, however, normal genital reflexes were observed in the majority of rats, albeit with a prolonged latency to the first erection relative to the control test. These same animals were, nonetheless, unable to achieve intromission when returned to the mating arena despite repeated mounting attempts. These data suggest that sensory input to the genitalia is generally necessary for the display of penile reflexes in the rat. However, stimuli associated with copulation can override the suppressive effect of sensory loss of these reflexes, presumably due to removal of supraspinal inhibition.

Animals↗

Further studies on alterations in male rat copulatory behavior induced by the dopamine-receptor agonist RDS-127.

Pharmacologic dopamine receptor stimulation by RDS-127 (2-N,N-di-n-propylamino-4,7-dimethoxyindane) resulted in qualitatively different changes in the mating pattern depending on the dose administered and time elapsed between treatment and behavioral observation. A low dose (0.25 mg/kg) selectively increased the latency to ejaculation whereas a high dose (3.0 mg/kg) decreased ejaculation latency and intromission frequency (both indicators of ejaculatory efficiency) when behavioral observations were begun 30 minutes after intraperitoneal administration. Intermediate doses (0.5, 1.0, and 2.0 mg/kg) did not alter the time required to achieve ejaculation but did lower the number of intromissions preceding ejaculation. These dose-dependent actions resemble the effects of dopaminomimetics (reported by others) on locomotor activity. When mating tests were conducted shortly (less than five minutes) after drug administration, the induction of ejaculation by the high dose was enhanced. At this time, as well as after a prolonged delay (two hours), signs of decreased arousal (longer intromission latencies) were also observed. However, the postejaculatory refractory period was altered in a time-dependent fashion, viz: it was shortened closest to the injection time, not altered 30 minutes after treatment, and increased two hours after RDS-127 administration. Finally, RDS-127 induced seminal emission (ex copula) in 2.9 +/- 0.9 (S.E.) minutes, and these emissions did not differ in weight from normal spontaneous (diurnal) seminal emissions. The RDS-127-induced seminal emission was not followed by a refractory period of similar magnitude to that seen after ejaculation in copula. The data are interpreted in terms of the involvement of dopamine receptor subtypes in the modulation of masculine sexual behavior.

Animals↗

Thymopoietin and levamisole in chronic granulomatous inflammation.

Two animal models were used to investigate the mode of action of levamisole and thymopoietin. Neither compound influenced the subcutaneous carrageenan air pouch. While thymopoietin inhibited the formation of cotton pellet granulomas, levamisole enhanced it. This supports the conclusions of clinical studies reported elsewhere that levamisole and thymopoietin do not act in the same way in rheumatoid arthritis.

Animals↗

Transepithelial voltage changes during prostatic secretion in the dog.

To define the nature of Na+, K+, and Cl- secretion by the dog prostate, the electrical potential difference between fluid in the prostatic urethra and venous blood was recorded during secretion provoked in pentobarbital-anesthetized dogs by electrically stimulating the hypogastric nerves or by administering pilocarpine intravenously. The resultant prostatic fluid samples as well as plasma samples taken before and/or after secretion were analyzed for these electrolytes. During secretion provoked by either means the transepithelial electrical potential difference, which was essentially zero at rest, became lumen negative, the maximum change (which was related to gland size) being about 4 mV. The time courses of both the potential change and the secretion of fluid were very similar. The Na+ concentration in both nerve- and pilocarpine-induced prostatic fluid was equal to that in plasma, whereas the K+ and Cl- concentrations were higher than in plasma. It is concluded that Na+ may move passively from plasma into prostatic fluid, perhaps via the paracellular route, but the movement of K+ and Cl- probably involves active transcellular transport.

Animals↗

Effects of diastolic transseptal pressure gradient on ventricular septal position and motion.

Despite the clinical prevalence of paradoxic interventricular septal (IVS) motion, its pathogenesis remains unclear. To assess the influence of the end-diastolic transseptal pressure gradient, we studied eight open-chest dogs during right ventricular (RV) volume loading (induced by opening a Dacron shunt between the pulmonary artery [PA] and right atrium), RV pressure loading (constriction of PA), and left bundle branch block (RV pacing). Ultrasonic crystals in the IVS and on the RV and left ventricular (LV) free walls (FW) allowed measurement of RV septal-to-free wall (S-FW) and LVS-FW diameters. Another set measured the anteroposterior (AP) diameter of the LV (LVAP). Two-dimensional and M mode echocardiograms confirmed IVS shape and motion pattern, respectively. RV volume load caused a reduction in mean transseptal end-diastolic pressure gradient from 2.1 to -2.6 mm Hg (p less than .001), with a concomitant increase in mean end-diastolic RVS-FW diameter of 2.5 mm (p less than .001) and a decrease in LVS-FW diameter of 2.8 mm (p less than .001). LVAP was unchanged. Echocardiograms confirmed a leftward IVS shift during diastole with paradoxic systolic motion. PA constriction and RV pacing caused similar directional changes in transseptal end-diastolic pressure gradients and diameters. Compared with control values, shunt opening and PA constriction also caused a small leftward shift of IVS at end-systole. Normalized data from all eight dogs revealed significant (p less than .001) correlations between reduction in LV-RV end-diastolic pressure gradients and increases in RVS-FW (r = .85) and decreases in LVS-FW (r = .80) diameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Measurement of plasma LH concentrations in aged male rodents by a radioimmunoassay and a radioreceptor assay.

Circulating plasma concentrations of LH from young mature (3-4 months old), middle-aged (15-18 months old) and aged (31-32 months old) male C57BL/6 mice, Syrian hamsters (3-4, 19-20 and 24-25 months old), Fischer 344 rats (3-4, 18-19 and 28-29 months old), Chinese hamsters (3-4, 19-20 and 29-30 months old) and Mongolian gerbils (3-4 and 19-22 months old) were analysed using a radioimmunoassay (RIA) and a radioreceptor assay (RRA). Male rats exhibited the greatest changes with advancing age: the oldest rats had an almost undetectable quantity of plasma LH, as measured by both assays. In contrast, the oldest male Syrian hamsters had significantly higher levels of LH than did younger animals. A significant decrease occurred in the amounts of LH detectable by RRA in middle-aged Chinese hamsters which was not evident with the RIA. There were no statistically significant differences in LH levels of C57BL/6 mice and gerbils with increasing age. The mean RRA:RIA ratios indicated that age-related differences in LH concentrations resulted from physiological changes in the secretion or the metabolic clearance of LH and not from changes in the biological potency of LH.

Aging↗

Efficacy of amoscanate against experimental schistosomal infections in monkeys.

The antischistosomal activity of oral doses of amoscanate (4-isothiocyanato-4'-nitrodiphenylamine) was determined in infected Cebus apella (capuchin monkeys) and Macaca mulatta (rhesus monkeys). In C. apella infected with Schistosoma japonicum or S. mansoni an initial dose of 10 mg/kg body weight did not alter fecal egg counts, but a subsequent dose of 25 mg/kg markedly reduced both egg counts and worm burdens; in animals infected with S. haematobium, a single dose of 25 mg/kg of amoscanate was similarly effective. Comparable schistosomicidal effects were also produced in S. japonicum- and S. mansoni-infected M. mulatta by single oral doses of 20 and 35 mg/kg, respectively. In both C. apella and M. mulatta the coadministration of single oral doses of 50 or 75 mg/kg of erythromycin attenuated the appearance of mutagenic metabolites of amoscanate in the urine but did not interfere with the antischistosomal action of amoscanate. In non-infected monkeys single oral doses of 75 mg/kg of amoscanate with or without erythromycin (50 mg/kg in C. apella or 75 mg/kg in M. mulatta) did not cause any major organ toxicity as revealed by gross and histopathologic examination, hematology, blood chemistry, electrocardiograms and urinalysis. The data indicate that in C. apella and M. mulatta, amoscanate is a relatively non-toxic antischistosomal agent effective orally against a broad spectrum of schistosome species.

Aniline Compounds↗

A comparison of etidocaine and lidocaine for retrobulbar anesthesia.

In this double-blind study of retrobulbar block for cataract surgery, 62 patients scheduled for cataract surgery were randomly assigned to treatment with either (1) lidocaine 2% with epinephrine 1:200,000 (21 patients); (2) etidocaine 1% plain (20 patients); or (3) etidocaine 1% with epinephrine 1:200,000 (21 patients). The time of onset of sensory and motor block after administration of the three drugs was the same. The duration of motor nerve block produced by etidocaine plain and by etidocaine with epinephrine was considerably longer than that produced by lidocaine with epinephrine, and fewer patients reported postoperative pain after either etidocaine plain or etidocaine with epinephrine than after lidocaine with epinephrine.

Acetanilides↗

The spectrum of cardiac rate and rhythm in normal newborns.

The distribution and variation of cardiac rate and rhythm in normal neonates has previously received little attention. This has made clinical assessment of dysrhythmia in newborns difficult. We therefore performed continuous 24-hour electrocardiography in 29 normal newborn subjects (age range, 1 to 6 days; mean, 3.5 days). The ECG tapes were then analysed in detail to define the normal range of cardiac rate, conduction intervals, and rhythm during waking and sleeping periods. Maximum sinus rate (awake) ranged from 150 to 222 beats per minute (mean, 192 +/- 16 [SD]), and minimum rate (awake) from 78 to 140 beats per minute (mean, 107 +/- 15). During sleep, the maximum rate ranged from 125 to 210 (mean, 168 +/- 23) and the minimum from 72 to 120 beats per minute (mean, 92 +/- 11). The maximum variation in rate for any individual during the 24-hour period ranged from 73 to 134 beats per minute (mean, 100 +/- 17). Sinus rhythm predominated with mild irregularity occurring episodically in 24 and moderate irregularity in 4 infants. An isolated atrial premature beat was present in 2 subjects, and an atrioventricular (AV) junctional escape rhythm occurred in one other after a sinus pause of 840 msec. Ventricular premature beats or AV conduction abnormalities were not observed. The corrected QT interval (QTc) ranged from 0.298 to 0.514 sec (mean, 0.390 +/- 0.026). The maximum variation in QTc over 24 hours ranged from 0.052 to 0.160 sec (mean, 0.097 +/- 0.028). We conclude that cardiac rhythm and conduction appear more stable in normal newborns than in older normal subjects and that bradycardia, conduction defects, and ventricular ectopy of the type recently reported in young normal adults seem to be more uncommon in the neonatal period.

Electrocardiography↗

Effects of a potent dopamine receptor agonist, RDS-127, on penile reflexes and seminal emission in intact and spinally transected rats.

Administration of RDS-127 (3.0 mg/kg) induced seminal emission within three minutes of IP injection and suppressed the display of penile reflexes in intact and spinally transected rats. In Experiment 1, RDS-127 was administered to intact, sexually experienced rats in a protocol previously demonstrated to selectively lower the ejaculatory threshold of copulating animals. The incidence of seminal emission was significantly elevated by RDS-127 but penile reflexes were present in only 8% of the drug-treated rats, compared to 59% of controls. In Experiment 2, seminal emission was induced 2.3 +/- 0.4 (S.E.) minutes from injection of RDS-127. Animals which responded to RDS-127 with multiple emissions had significantly lower ejaculation latencies during copulatory tests conducted prior to drug treatment than animals which had no or only single seminal emissions following RDS-127 injection. Spontaneous seminal emission in the 3 day period initiated 2 hours after RDS-127 injection was unaffected by the drug. Spontaneously produced plugs were approximately twice the weight of those induced by RDS-127. In Experiment 3, seminal emission was induced in spinally transected rats 1.7 +/- 0.4 minutes following RDS-127 administration, whereas drug treatment attenuated the enhancement of penile reflexes observed following midthoracic spinal transection. These experiments suggest that a spinally-mediated dopaminergic mechanism is capable of stimulating seminal emission acutely in the rat and inhibiting the display of penile reflexes by the supine animal.

Animals↗

Hormonal responses accompanying fear and agitation in the squirrel monkey.

The adrenocortical and gonadal responses of 14 male monkeys were evaluated during four experimental conditions in order to evaluate the influence of social interactions on endocrine responsiveness. Plasma hormone levels were determined during the establishment of social relations, after 60-min exposures to a novel environment, after 60-min exposures to a snake, and 60 min after ACTH administration. Both adrenal and gonadal secretion changed significantly during the first day after social relations were established, although only dominant males showed increases in testosterone, whereas cortisol levels rose in all subjects. Increases in cortisol, but not testosterone, were also observed following exposure to novelty or a snake. The presence of a social partner reduced signs of behavioral disturbance during these test conditions, although the adrenal responses were equivalent or greater than when tested alone. This finding qualifies earlier research which indicated that social support was beneficial for reducing stress when squirrel monkeys were tested in larger groups in their home environment.

Adrenocorticotropic Hormone↗

Effects of a novel dopamine-receptor agonist RDS-127 (2-N,N-di-n-propylamino-4,7-dimethoxyindane), on hormone levels and sexual behavior in the male rat.

Selective changes in the mating pattern occurred 30 minutes following administration of RDS-127 (3.0 mg/kg, IP) to sexually experienced adult male rats. Marked decreases in intromission frequency and ejaculation latency were observed. These data indicate a potent effect upon conummatory mechanisms underlying copulatory behavior. The lack of effect upon arousal state was further demonstrated utilizing a "mounting test" (in which the penis is anesthetized by topical application of tetracaine hydrochloride). No difference in mounting behavior was seen. Seminal plugs were noted in a large percentage of treated animals at the time of anesthetic application. Additionally, a six-fold decrease in plasma prolactin and a lesser decrement in plasma luteinizing hormone were evident. Finally, in sexually experienced castrate animals, RDS-127 induced mounting in two thirds and intromissive and ejaculatory patterns in one third of the treated animals, 35 days postcastration. These effects were greatly attenuated by 56 days postcastration. The selective alteration of consummatory mechanisms, with little or no effect upon arousal status, suggests a neurochemical separation of these two components in the intact male rat.

Animals↗