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Biomedical subjects

R J Levin

Publications and source records attributed to R J Levin.

At least 55 records · Page 3Linked to original sources

Fluid hypersecretion induced by enterotoxin STa in nutritionally deprived rats: jejunal and ileal dynamics in vivo.

The effect of luminal enterotoxin Escherichia coliSTa on fluid transport across the jejunum and ileum of fed, starved (72 h) and chronically undernourished (50% control food intake for 21 days) rats was assessed in vivo using a gravimetric technique. Dose-response curves for net fluid secretion (stimulated-basal (30 min)-1) activated by 5,50 and 500 ng ml-1 STa were obtained for jejuna and ilea from fed, starved and chronically undernourished rats. Compared to the fed rats, both dietary deprivations showed enhanced net fluid secretion at 500 ng ml-1, but only the jejunum from chronically undernourished rats showed significantly enhanced secretion at 5 and 50 ng ml-1. Net fluid secretory responses to a standard dose of STa (500 ng ml-1) were monitored in the jejuna and ilea of fed, starved and chronically undernourished rats at 30, 60, 90 and 120 min. The pattern in jejuna and ilea from fed rats was very different; the jejunal secretion over 30 min was transient, but ileal secretion increased continuously to a maximum at 120 min. In both jejunum and ileum from starved rats, the secretory response to STa at 30 min was significantly greater than that in fed rats and subsequently remained near this level. In the jejunum from chronically undernourished rats, the net fluid secreted in response to STa was greatly enhanced at 30 and 60 min, but not at 90 min. The ileal response was significantly greater than that in the fed rats at 30 and 120 min. Luminal procaine (10 mM) selectively increased fluid absorptive tone in the jejunum from fed rats, reduced STa-induced fluid secretion in the ileum from undernourished rats, but had no effect on STa in the jejunum from undernourished rats or in the jejunum or ileum from starved rats. Luminal 8-bromo-cyclic GMP (1 mM) had no effect on basal absorptive tone in the jejunum of fed or chronically undernourished rats, but enhanced the secretory tone of jejunum from starved rats. In the ileum, however, while 8-bromo-cyclic GMP enhanced secretory tone in the fed and starved conditions, it still had no action in the chronically undernourished state. The enhanced fluid secretion observed in the jejunum and ileum of the starved and undernourished rats compared to the fed rats supports previous in vitro findings of an increased electrogenic secretion induced by STa in these dietary deprivations. The fluid hypersecretion could be a cause of the increased severity of diarrhoea often observed in undernourished and starved humans.

Animals↗

Role of the enteric nervous system in the maintained hypersecretion induced by enterotoxin STa in the nutritionally deprived intestine.

Electrogenic (Cl-) secretion was measured as the short circuit current (Isc, microA/cm2) across muscle-stripped sheets of jejunum and ileum incubated in vitro after removal from fed rats, rats starved for three days, and chronically undernourished rats (50% of fed control intake for 21 days). Concentration and Isc response curves for serially-added mucosal Escherichia coli STa enterotoxin showed that the rats which had undergone dietary deprivation had a larger secretory Isc maximum but the ED50 values were unchanged compared with fed animals. In fed intestine the action of STa was transient, with an Isc peak and subsequent decay to the baseline over 60 minutes but in the undernourished intestine the response consisted of a significantly greater peak than that of the fed state (jejunum = 94%; ileum = 168%) and the Isc was maintained at or near the peak for at least 60 minutes. The starved intestine had a less well developed maintenance of its enhanced peak Isc. Serosal tetrodotoxin (1 microM) had no effect on the initial peak Isc values but caused a decay of the maintained Isc down to the basal or fed levels in the starved and, especially, in the undernourished intestines. Thus, dietary deprivation, especially chronic undernutrition, enhances the maximum electrogenic secretion due to STa and creates a new neural path in the submucosal plexus that, when activated by STa, maintains its enhanced secretory action. Its putative role in exacerbating secretory diarrhoea in malnourished human subjects could be an important component underlying the known relation between malnourishment and the increased severity of diarrhoea.

Animals↗

Evaluation of vaginal and perineal area during the use of external sanitary protection throughout the menstrual cycle.

A clinical study evaluated potential external genital effects associated with the use of sanitary protection. The subjects used either a pad with traditional cellulose absorbent core or one containing cellulose and absorbent gelling material. Assessments included objective (transepidermal water loss, vaginal pH) and semi-quantitative subjective--methods (skin irritation grading, gynaecological inspection). No statistical or clinical significant differences for any of the parameters evaluated between the groups using the two pads, or compared to the non-pad control period, were found. The parameters used to study the effects on the genital area of an external sanitary product appear appropriate. No significant changes were observed for either of the two pads during daily use for two menstrual cycles.

Adult↗

Increased vaginal blood flow induced by implant electrical stimulation of sacral anterior roots in the conscious woman: a case study.

The sacral anterior nerve roots were stimulated in a conscious female paraplegic by means of an intradural implanted Finetech/Brindley stimulator activated by inductive radio signals. Changes in vaginal blood flow were monitored by a photoplethysmograph. Stimulating S2 and S3 (but not S4) caused significant increases in vaginal pulse amplitude indicating genital vasodilation and increased blood flow.

Adult↗

Electrogenic ion secretion in proximal, mid and distal colon from fed and starved mice.

1. Electrogenic ion transport was monitored in vitro as the short-circuit current (Isc in microA/cm2) across proximal, mid and distal colon removed from fed and 48 hr-starved Swiss albino mice (Mus muscaris). 2. Electrogenic secretion was induced either with serosal bethanechol (muscarinic agonist), DMPP (nicotinic agonist) or dibutyryl-cyclic AMP (DbcAMP). Proximal and distal colon from starved mice showed greater electrogenic secretion in response to bethanechol than those the fed controls while DMPP and DbcAMP did not activate the hypersecretion. 3. In the distal colon, starvation induced a large increase in the basal Isc that was unaffected by mucosal amiloride but was inhibited by tetrodotoxin (TTX) and by diphenylamine-2-carboxylic acid (DPC) unlike the fed basal Isc. Bethanechol activated a biphasic response consisting of a transient decrease in the Isc followed by a sustained increase both of which were significantly greater in the starved than the fed tissue and were inhibited by TTX, DPC and atropine but not hexamethonium. 4. Starvation enhances the secretory response to muscarinic activation in proximal and distal colon and induces an increased basal electrogenic (Cl-) secretion in the distal colon stimulated by an augmented neural tone.

Animals↗

Enterocytes on rat jejunal villi but not in the crypts posses m3 mRNA for the M3 muscarinic receptor localized by in situ hybridization.

Localization of m3 mRNA, for the expression of the M3 muscarinic receptor, along the crypt-villus axis, was undertaken in rat jejunum by in situ hybridization. While enterocytes on the lower two-thirds of the villi showed the presence of m3 mRNA it was absent in the crypt enterocytes. This indicates that the final locus of muscarinically activated jejunal secretion is mediated by the M3 receptor on the enterocytes of the villi and not via the crypt cells.

Animals↗

Enhanced electrogenic secretion in vitro by small intestine from glucagon-treated rats: implications for the diarrhoea of starvation.

Glucagon treatment of fed rats (50 micrograms I.P. every 6 h for 3 days) induces significant increases in vitro of the basal short-circuit currents of the jejunum (52%) and proximal ileum (81%) and in their electrogenic secretory responses to stimulation by bethanechol, a muscarinic agonist. The results support a role for glucagon in the intestinal hypersecretion observed in starvation and nutrient deprivation.

Animals↗

Dietary restriction sensitizes the rat distal colon to aldosterone.

1. The effects of starvation and undernutrition were assessed on rat colonic electrogenic Na+ absorption in fed controls, 72 h starved and acute undernourished (fed one-third of the control group's daily food intake for up to 9 days). The basal short-circuit currents (Isc) of three segments of rat colon (proximal, mid- and distal), stripped of their external muscle layers were monitored before and during addition of 0.1 mM-mucosal amiloride. The decrease in Isc was used as the measure of the electrogenic Na+ absorption. 2. Acute undernutrition and to a lesser extent 72 h starvation elevated the basal Isc only in the distal colon. The increase was inhibited by amiloride (0.1 mM, mucosal) indicating that it was due to electrogenic Na+ transport. 3. Allowing the 9 days acute undernourished rats to drink 0.9% NaCl failed to prevent the increase in the basal Isc in the distal colon but it was reduced by administration of spironolactone. 4. Adrenalectomy completely abolished the increased basal Isc in the distal colon induced by the 9 day undernutrition. However, the plasma aldosterone levels in the fed and 9 day undernutrition groups were not significantly different. 5. Injection of aldosterone into adrenalectomized rats drinking 0.9% NaCl and which were undernourished for 9 days induced a large increase in their distal colonic Isc which was inhibited by mucosal amiloride. Similar treatment of sham-operated rats on 0.9% NaCl or adrenalectomized control fed rats on 0.9% NaCl had no effect on the distal colonic Isc. 6. The results indicate that acute undernutrition for 9 days makes the distal colonic epithelium more sensitive to the prevailing plasma aldosterone level allowing an enhanced electrogenic Na+ absorptive capacity to be induced.

Adrenalectomy↗

Vitamin A deficiency and colonic electrogenic absorption and secretion in the rat.

The effects of vitamin A deficiency on electrogenic transport in the colon were examined in rats made vitamin A deficient at weaning by feeding a vitamin A deficient diet for 40 days. A pair fed control group was given the same diet but supplemented with soluble vitamin A in their drinking water. The basal and stimulated electrogenic secretory and absorptive functions of the muscle stripped proximal, mid, and distal colon were examined in vitro using the short circuit current (Isc) as the index of net ion transport. A significant increase in the basal and secretory Isc (mainly Cl-ions) induced by the cholinergic agonist bethanechol was observed in the mid-colon of the vitamin A deficient rats. In the distal colon, however, vitamin A deficiency caused a significant reduction in both the basal and secretory Isc response to bethanechol compared with the vitamin A supplemented pair fed control. Secretory Isc induced by dibutyryl cyclic adenosine monophosphate was not significantly altered by vitamin A deficiency. The condition abolished the response of the distal colon to luminal amiloride (0.1 mmol/l). Thyroid hormone induced reduction in the distal colonic response to aldosterone is implicated in this lack of response. This is the first experimental linkage between vitamin A action, the thyroid hormone and aldosterone on colonic function. The colonic changes induced by vitamin A deficiency, namely hypersecretion and a reduced electrogenic distal absorptive function, together with the previously described small intestine hypersecretion may be the underlying basis for the diarrhoea observed in human and animal vitamin A deficiency.

Aldosterone↗

Intestinal hypersecretion of the refed starved rat: a model for alimentary diarrhoea.

Fluid transport was gravimetrically measured in vivo in the duodenum, jejunum, and ileum of anaesthetised fed, 72 hour starved and 72 hour starved rats refed for up to five days after starvation. Basal unstimulated fluid transport was monitored by instilling 0.9% NaCl into the lumen and measuring the gain or loss in weight of the closed intestinal loop. Fluid was absorbed in all the areas of the intestine in the fed rats. Increasing basal fluid absorption was observed in the duodenum over the three days of starvation but in the jejunum there was no significant change. In the ileum, the pattern was very different, on day 1 the fluid was absorbed but on days 2 and 3 there was an increasing secretion of fluid. Refeeding the rats with their normal diet restored the basal absorption of fluid in the duodenum within 24 hours, had no effect in the jejunum but in the case of the ileum the hypersecretion of fluid observed in the day 3 starved rat was maintained on day 1 of refeeding, increased further on day 2, decreased on day 3 but returned to absorption on day 4. The normal absorption was restored to the ileum on day 5 of refeeding. Fluid secretion was induced in all the rat groups by bethanechol (ip 60 micrograms/kg bw) a stable cholinergic agonist, PGE2 (ip 10 micrograms/kg (bw) and E coli STa (luminally instilled, 500 ng/ml) a secretory enterotoxin. All the secretagogues gave enhanced secretion compared with the fed by day 2 of starvation which increased considerably on day 3. Refeeding returned their secretion back to the fed level in the duodenum within 24 hours, in the jejunum within 48 hours but in the ileum their induced secretion on day 2 of refeeding was greater than that of the day 2 of refeeding was greater than that of day 3 starved and took until day 4 to return to the fed levels for behanechol and PGE2 and until day 5 for E. coli STa. This behaviour of rat small intestine showing even greater hypersecretion in the refed state than the starved mimics the human condition of alimentary induced diarrhoea where incautious feeding of starved humans induces severe, often lethal diarrhoea. The refed starved rat appears to be a possible model for this condition.

Animals↗

VIP, vagina, clitoral and periurethral glans--an update on human female genital arousal.

The sexually quiescent human vagina is a just moist, potential space with a minimal blood flow and very low luminal oxygen tension. The first measurable sign of sexual arousal is an increase in the blood flow. This creates the engorged condition, elevates the luminal oxygen tension and stimulates the production of surface vaginal fluid by an increased plasma transudation that saturates the fluid reabsorptive capacity of the epithelium. The vaginal lubrication created allows painless penile penetration and coital movements. The mechanisms underlying the changes appear to be mediated by Vasoactive Intestinal Peptide (VIP). VIP is present in nerves closely applied to blood vessels in the vaginal wall. Administration of VIP either intravenously, or by subepithelial injection in the vaginal wall, increases vaginal blood flow and induces vaginal fluid production. Increases in vaginal blood flow by sexual arousal are not blocked by atropine injection indicating that cholinergic mechanisms are unimportant. All the present evidence suggests that the local vaginal release of VIP induces the vaginal changes of arousal. Discourse on vaginal and pudendal anatomy (Sevely, 1987) has proposed that the female glans of the clitoris is not the true homologue of the penile glans because it has no urethral opening. The speculative suggestion is that the true female glans is the area surrounding the urethral opening (which has no specific anatomical name). Preliminary studies indicate that the area of this tissue (periurethral glans) decreases on vaginal penile insertion and reappears on withdrawal indicating that it is moved during coitus. How important such movement is to stimulate erotic sensation and how sensitive this area is to erotic stimulation are unanswered questions.

Clitoris↗

Cumulative dose-response curves for bethanechol-induced electrogenic secretion in rat jejunum in vitro: is tachyphylaxis a significant factor?

Electrogenic secretion was monitored as the short-circuit current (Isc) by an automatic voltage clamp across the isolated rat jejunum incubated in vitro. Responses to consecutive additions of bethanechol (1 mM) to the serosal surface showed tachyphylaxis. Addition of prostaglandin E2, however, after a single dose of 1 mM-bethanechol, induced an undiminished Isc response indicating that the tachyphylaxis was homologous. Dose-response curves for serosal applications of bethanechol obtained by serial-cumulative addition did not show tachyphylaxis when compared with those from a non-cumulative technique. The method of automatically recording the intestinal Isc with serial-cumulative addition of a serosal secretagogue gives dose-response curves free from tachyphylaxis.

Animals↗

5-Hydroxytryptamine induces electrogenic secretion and simultaneously activates a modulating inhibitory neural circuit in rat small intestine in vitro.

5-Hydroxytryptamine (5-HT) induces electrogenic secretion across rat jejunum and ileum in vitro expressed as an increase in the short-circuit current. Enhancement of this secretory response by previous serosal addition of atropine (1 microM), hexamethonium (0.2 microM) or yohimbine (0.2 microM), especially in the ileum, indicated that 5-HT simultaneously activates an anti-secretory, inhibitory, enteric, neural, cholinergic-adrenergic pathway (ENCAP). A similar inhibitory ENCAP activated by 5-HT has previously been characterized in rat colon in vitro.

Animals↗

Segmental heterogeneity of rat colonic electrogenic secretion in response to the bacterial enterotoxin Escherichia coli STa in vitro.

The effects of the bacterial toxin Escherichia coli STa on electrogenic secretion in proximal, mid and distal rat colon were examined in vitro using the short-circuit current (Isc) as an index of secretion. All areas showed toxin-elevated Isc which was reduced by bumetanide. The proximal colon was the most sensitive (lowest ED50) but displayed the lowest maximal increase in Isc, the mid colon had the largest maximal electrogenic response while the distal colon proved to be the least sensitive (highest ED50). Atropine (1 microM) and tetrodotoxin (1.25 microM) reduced the maximum Isc response to STa by up to 42%, indicating that the enteric nervous system may be partly involved in the response.

Animals↗

Vitamin A deficiency and small intestinal secretory function in the rat.

The influence of vitamin A on the functions of the small intestine was examined in rats made vitamin A deficient for 40 days by feeding a special diet after weaning and in pair fed vitamin A deficient rats that were given supplementary vitamin A (240 IU/day) in their drinking water. The basal and stimulated electrogenic secretory and absorptive functions of the jejunum and proximal and distal ileum removed from these rats were examined in vitro using the short circuit current as the index of transport activity. The basal short circuit current in the jejunum and proximal ileum was not significantly different but that of the distal ileum was lower. Electrogenic glucose transfer was not significantly affected by the vitamin deficiency. Cholinergic stimulation using the M1/M2 agonist bethanechol showed a greatly enhanced electrogenic secretion in the jejunum of the deficient rats while secretion stimulated by dibutyryl cyclic adenosine monophosphate was significantly greater in their distal ilea compared with the supplemented group. The vitamin deficiency also disrupted the normal higher/lower hierarchical pattern of transport activity between the proximal and distal ileum. The enhanced secretory activity of the vitamin A deficient small intestine offers a putative explanation for the well known relation between vitamin A deficiency and diarrhoea found in humans.

Animals↗

Erection and ejaculation in man. Assessment of the electromyographic activity of the bulbocavernosus and ischiocavernosus muscles.

Electromyographic (EMG) recordings were obtained by concentric needle electrodes from the bulbocavernosus (BC) and ischiocavernosus (IC) muscles in 7 human volunteers during excitement to erection and subsequent ejaculation. Simultaneous registration of the time course and volume of each expressed spurt of semen was obtained using an aluminium pan suspended in front of the subject's penis on a force transducer the output of which was charted with the EMG activity. The BC and IC muscles showed no EMG activity during erection and detumescence cycles induced by visual sex stimulation. In 5 of 7 subjects, the first EMG burst of the BC in ejaculations induced by masturbation was not correlated with an expelled spurt of semen as were subsequent bursts. However, only 26 to 60% of the total number of EMG bursts were accompanied by expulsion of a spurt of semen. There thus appears to be a large safety factor in the striated muscle expulsive mechanism. Oral phenoxybenzamine treatment in 2 subjects did not significantly affect either the number of EMG bursts of the BC or the subjective pleasure of the orgasm but did significantly reduce the volume of semen expelled. Semen volume does not appear to be a unique determinant of the pleasure felt or the trigger for ejaculation.

Adult↗