Biomedical subjects

G Lopez

Publications and source records attributed to G Lopez.

At least 37 records · Page 2Linked to original sources

PubMed1998

Isolation and characterization of iridoviruses from the giant toad Bufo marinus in Venezuela.

In this communication we describe for the first time the isolation of 7 iridoviruses from the toad Bufo marinus and an unknown species of frog Leptodactylus in Venezuela, South America. The viruses are icosahedral with electron-dense cores, each of which is surrounded by an inner membrane, capsid and a cell-derived envelope. The virus(es) have an average vertex to vertex diameter of 160 nm and replicate in the cytoplasm of a range of cell lines. Within the cytoplasm of infected cells, rarefied areas could be observed; structures lacked cellular organelles and contained complete, empty and developing viruses. Results from antigen-capture enzyme-linked immunosorbent assays (ELISA) with polyclonal antibody raised against epizootic haematopoietic necrosis virus (EHNV) indicated cross-reactivity between these isolates, Bohle iridovirus (BIV) and frog virus 3 (FV3). Comparison of polypeptide and genomic profiles indicated that the Venezuelan viruses shared many polypeptides of equivalent molecular weight with type species FV3. There were, however, differences between the group of Venezuelan viruses and FV3 and BIV. The viruses belongs to the family Iridoviridae and the genus Ranavirus.

Animals↗

PubMed1998

Giant toads Bufo marinus in Australia and Venezuela have antibodies against 'ranaviruses'.

A serological survey was conducted for antibodies against 'ranaviruses' in the giant toad Bufo marinus in Australia and Venezuela. Sera containing antibodies against 'ranaviruses' were found in both countries. In Australia positive antibodies were identified in populations throughout most of the known range of B. marinus. Results were confirmed by immunofluorescence and immunoelectron microscopy where a characteristic staining pattern of 'ranaviruses' in infected cells was observed. Whilst a 'ranavirus(es)' has been isolated from populations of B. marinus in Venezuela, no virus has been isolated from Australian B. marinus populations. The significance of 'ranavirus' sero-positive B. marinus in Australia is discussed.

Animals↗

PubMed1998

Fluorescence lifetime spectroscopic imaging with measurements of photon migration.

Frequency-domain measurements of photon migration are coupled with a model of fluorescence generation and propagation in order to develop a method for reconstructing maps of fluorescent properties within interior tissue volumes from exterior measurements at the air-tissue interface. Simulation results confirm the feasibility of optical imaging through the use of exogenously administered contrast agents on the basis of fluorophore decay kinetics and yield. Experimental measurements using single-pixel and multipixel devices illustrate that the contrast owing to exogenous fluorescence exceeds that owing to absorption or scattering caused by endogenous chromophores or tissue structure and owing to absorption caused by exogenous contrast agents.

Diagnostic Imaging↗

PubMed1998

Pharmacology of the peptidomimetic, MEN 11149, a new potent, selective and orally effective tachykinin NK1 receptor antagonist.

In this study we investigated the pharmacological properties of MEN 11149, 2-(2-naphthyl)-1-N-[(1R,2S)-2-N-[1(H)indol-3-ylcarbonyl]aminocy clohexanecarbonyl]-1-[N'-methyl-N'-(4-methylphenylacetyl)]di aminoethane, a novel partially retro-inverse pseudo peptide antagonist of tachykinin NK1 receptors. MEN 11149 potently inhibits the binding of [3H]substance P to tachykinin NK1 sites in IM9 cells (pKi = 8.5 +/- 0.1). The compound is highly specific for the human tachykinin NK1 receptors, since it has negligible effects (pKi < 6) on the binding of specific ligands to tachykinin NK2, NK3 receptors and a battery of central and peripheral receptors or ion channels. The tachykinin NK1 receptor antagonism of MEN 11149 appears to be insurmountable since, in saturation binding experiments, both K(D) and Bmax are significantly affected by incubation with the compound (1-30 nM). In isolated guinea-pig ileum, MEN 11149 (0.1-100 nM) shifts to the right in a non-parallel way the substance P methyl ester-induced cumulative concentration-response curve with progressive inhibition of the maximal response (pK(B) = 9.6 +/- 0.1). When tested for reversibility at 5 nM in the same preparation, the compound displays a slow dissociation rate compared to the fast dissociation rate with FK888 (N2-[(4R)-4-hydroxy-1-(1-methyl-1H-indol-3-yl)carbonyl-L-prolyl]-N-methy l-N-phenylmethyl-L-3-(2-naphthyl)alaninamide) at 5 nM. In the same preparation, MEN 11149 (10 microM) did not affect the cumulative concentration-response curve to acetylcholine. In vivo, MEN 11149 dose dependently antagonizes [Sar9,Met(O2)11]substance P-induced bronchoconstriction in anaesthetized guinea-pigs (ID50 = 83 +/- 31 nmol/kg i.v.). The duration of the effect exceeds 3 h. MEN 11149 does not affect the bronchoconstriction induced by neurokinin A. The compound dose dependently inhibits [Sar9,Met(O2)11]substance P-induced plasma protein extravasation in guinea-pig bronchi whether administered intravenously (ID50 = 0.22 +/- 0.02 micromol/kg) or orally (ID50 = 0.97 +/- 0.21 micromol/kg). These results demonstrate that MEN 11149 is a potent, highly selective and orally effective insurmountable antagonist of tachykinin NK1 receptors with a long duration of action.

Administration, Oral↗

PubMed1998

Inflammatory and motor responses by tachykinins in the guinea-pig oesophageal sphincter.

1. The aim of this study was to characterize the tachykinin receptors involved in producing plasma protein extravasation and contractile responses of the guinea-pig oesophageal sphincter. 2. In anaesthetized guinea-pigs, the selective tachykinin NK-1 receptor agonist [Sar9,Met(O2)11]substance P produced plasma protein extravasation (PPE) which was not affected by the treatment with the tachykinin NK-2 receptor antagonist MEN 10627 (1 micromol kg(-1) i.v.) or the histamine H1-receptor antagonist, diphenhydramine (34.5 micromol kg(-1) i.v.). However, the [Sar9,Met(O2)11]substance P-induced PPE was blocked by the previous administration of the peptide tachykinin NK-1 receptor antagonist FK 888 or by the non-peptide antagonist SR 140333, yielding ED50 values of 1.1 +/- 0.2 and 0.01 +/- 0.004 micromol kg(-1) i.v., respectively. 3. The tachykinin NK-2 or NK-3 receptor agonists [beta-Ala8]neurokinin A (4-10) or [MePhe7]neurokinin B, respectively, produced a weak PPE at high doses. The effect of [MePhe7]neurokinin B-induced PPE was inhibited by SR 140333. 4. In the guinea-pig isolated oesophageal sphincter, [Sar9,Met(O2)11]substance P did not exert any contractile effect up to 10 microM. The selective tachykinin NK-2 receptor agonist ([beta-Ala8]neurokinin A (4-10), produced concentration-dependent contractions (pD2 = 7.6 +/- 0.03) which were inhibited by the selective tachykinin NK-2 receptor antagonist, MEN 10627 (pA2 = 8.6 +/- 0.1). Also, the tachykinin NK-3 receptor selective agonist [MePhe7]neurokinin B induced concentration-dependent contractile responses, but these responses were inhibited by MEN 10627. 5. Altogether, these data indicate that the stimulation of tachykinin NK-1 receptor produces a vascular inflammatory response, while activation of tachykinin NK-2 receptors mediate the contraction of the guinea-pig oesophageal sphincter.

Animals↗

PubMed1998

Single-dose azithromycin for Chlamydia in pregnant women.

OBJECTIVE: To assess the efficacy and occurrence of severe side effects associated with the use of a single dose of azithromycin in the treatment of Chlamydia trachomatis in pregnant women. STUDY DESIGN: Patients and their sexual partners were randomized into three treatment groups: both the patient and her sexual partner received a single dose of azithromycin (group 1); the patient was given a standard course of erythromycin, while her partner was given a standard course of tetracycline (group 2); and the patient was given a single dose of azithromycin with the sexual partner given a standard course of tetracycline (group 3). Group 3 was included in order to assess the relative efficacy of tetracycline with respect to the use of azithromycin among patients and to indirectly assess possible patient reinfection by sexual partners. RESULTS: With respect to the cure rate, 4.5% of study participants given azithromycin has positive cultures vs. 21.1% of patients given erythromycin or tetracycline (P = .018). With respect to side effects severe enough to warrant a change in medication, 7.4% of patients receiving azithromycin reported suffering such side effects vs. 38.8% of patients given erythromycin (P = .02). Among sexual partners, 28.6% given tetracycline reported severe side effects vs. none of those given azithromycin (P = .03). CONCLUSION: Azithromycin in the treatment of C trachomatis in pregnant women substantially improved the cure rates while substantially reducing the occurrence of severe side effects associated with the use of a standard course of erythromycin. Since both tetracycline and erythromycin are known to be effective against C trachomatis infection, the improved efficacy of azithromycin is probably due to noncompliance with the multidose, multiday regimen associated with the use of these two antibiotics.

Anti-Bacterial Agents↗

PubMed1997

Histological diagnosis of precancerous lesions of the stomach: a reliability study.

BACKGROUND: Within the framework of a chemoprevention trial on stomach cancer, two substudies based on repeat measurement were undertaken to evaluate reliability of histological diagnoses of gastric precancerous lesions. METHODS: A subgroup of 45 subjects received two endoscopies separated by a period of one month. The two biopsies were reviewed by a single pathologist. A second subsample of 50 subjects had a single endoscopy and the biopsy results were reviewed by two pathologists. Agreement between the two diagnoses was assessed by Cohen's Kappa and by repeat frequency. RESULTS: When the same samples were reviewed by the pathologists involved in the trial, agreement was very high for advanced lesions (repeat frequency = 0.96 for intestinal metaplasia and 1.00 for dysplasia) but lower for less advanced lesions (repeat frequency = 0.73 for superficial gastritis and chronic gastritis, 0.65 for atrophic gastritis). When the same pathologist reviewed two sets of biopsies taken less than 2 months apart, the combination of random observer error and biopsy sampling error gave rise to quite low agreement, especially for early lesions, mainly attributable to biopsy sampling error. Comparison of diagnoses made at routine reading and at review by the same pathologist and by different pathologists showed substantial overall agreement with the exception of one pathologist for whom agreement was moderate. CONCLUSIONS: These results confirm that misclassification of histological diagnosis may be a relevant problem in chemoprevention trials of stomach cancer, more so when baseline diagnosis is taken into account in the analysis to estimate progression and regression rates of precancerous lesions. Further, the results suggest that misclassification is limited to early lesions, while diagnostic reliability of severe lesions is quite high.

Adult↗

PubMed1997

Fluorescence and absorption contrast mechanisms for biomedical optical imaging using frequency-domain techniques.

The ability to optically image or detect diseased tissue volumes located deep within tissues depends upon the degree of contrast provided by differences in local optical properties. In this report, we show that the exogenous contrast offered by fluorescent compounds is superior to that provided by nonfluorescing, light-absorbing compounds when time-dependent measurements are employed. In addition, we show that the induced contrast is not only moderated by the preferential uptake of fluorescent agents into diseased tissue volumes of interest but also by the fluorescent optical properties and the fluorescence dynamics in the specific tissue volume. Using tissue phantom studies, we demonstrated experimentally that near-infrared-absorbing and fluorescent dyes such as indocyanine green can provide detection of diseased tissue volumes from fluorescence measurements made at the periphery of tissue when there is perfect, 100-fold and 10-fold partitioning in diseased tissues over that in surrounding normal tissues. Experimental results of common laser dyes show the contrast is also mediated by the quantum yield and lifetime parameters that may be dependent upon the local tissue environment.

Diagnosis↗

PubMed1997

Mutations in the conserved C-terminal sequence in thyroid hormone receptor dissociate hormone-dependent activation from interference with AP-1 activity.

A short C-terminal sequence that is deleted in the v-ErbA oncoprotein and conserved in members of the nuclear receptor superfamily is required for normal biological function of its normal cellular counterpart, the thyroid hormone receptor alpha (T3R alpha). We carried out an extensive mutational analysis of this region based on the crystal structure of the hormone-bound ligand binding domain of T3R alpha. Mutagenesis of Leu398 or Glu401, which are surface exposed according to the crystal structure, completely blocks or significantly impairs T3-dependent transcriptional activation but does not affect or only partially diminishes interference with AP-1 activity. These are the first mutations that clearly dissociate these activities for T3R alpha. Substitution of Leu400, which is also surface exposed, does not affect interference with AP-1 activity and only partially diminishes T3-dependent transactivation. None of the mutations affect ligand-independent transactivation, consistent with previous findings that this activity is mediated by the N-terminal domain of T3R alpha. The loss of ligand-dependent transactivation for some mutants can largely be reversed in the presence of GRIP1, which acts as a strong ligand-dependent coactivator for wild-type T3R alpha. There is excellent correlation between T3-dependent in vitro association of GRIP1 with T3R alpha mutants and their ability to support T3-dependent transcriptional activation. Therefore, GRIP1, previously found to interact with the glucocorticoid, estrogen, and androgen receptors, may also have a role in T3R alpha-mediated ligand-dependent transcriptional activation. When fused to a heterologous DNA binding domain, that of the yeast transactivator GAL4, the conserved C terminus of T3R alpha functions as a strong ligand-independent activator in both mammalian and yeast cells. However, point mutations within this region have drastically different effects on these activities compared to their effect on the full-length T3R alpha. We conclude that the C-terminal conserved region contains a recognition surface for GRIP1 or a similar coactivator that facilitates its interaction with the basal transcriptional apparatus. While important for ligand-dependent transactivation, this interaction surface is not directly involved in transrepression of AP-1 activity.

Amino Acid Sequence↗

PubMed1996

Genetic predisposition and environmental factors leading to the development of insulin-dependent diabetes mellitus in Chilean children.

This study was designed to examine the hypothesis that some environmental factors increase the risk for insulin-dependent diabetes mellitus. Data on dietary history was collected from 80 diabetic children from the Santiago de Chile Registry and from 85 nondiabetic control subjects who were comparable in terms of age, sex, and ethnic characteristics. Early exposure was defined as the ingestion of food sources other than maternal milk before 3 months of age. To define genetic susceptibility to insulin-dependent diabetes mellitus each subject was typed in terms of HLA DQA1 and DQB1, and the possible conformation of susceptible heterodimers was considered as a risk marker. Fewer children were exclusively breast fed in the diabetic group than in the control group (21.55 +/- 15.05 vs 33.95 +/- 20.40 weeks, P<0.01). In addition, exposure to cow's milk and solid foods occurred earlier in the diabetic group than in the control group (15.90 +/- 10.95 vs 21.15 13.65 and 16.85 +/- 10.25 vs 21.20 +/- 12.35 weeks, P<0.05). Our data show that a short duration of breast-feeding and early exposure to cow's milk and solid foods may be important factors in the development of insulin-dependent diabetes mellitus. The high relative risk observed in individuals genetically predisposed indicates an interaction effect between genetic and environmental components.

Adolescent↗

PubMed1996

Prevalence of precancerous lesions of the stomach in Venezuela.

Gastric biopsies from 1477 participants in a chemoprevention trial for precancerous lesions of the stomach in Venezuela were evaluated for the prevalence of precancerous lesions and Helicobacter pylori infection. These study subjects were selected from participants in an early detection program for gastric cancer using double-contrast X-ray. Overall, 94% had some type of chronic gastritis (CG) and were positive for H. pylori using Giemsa stain, 49% had atrophic gastritis, 34% had intestinal metaplasia (IM), and 6.5% had dysplasia. There were only three subjects (0.2%) with normal gastric mucosa, and 4% had only superficial gastritis. The prevalence of all of these precancerous lesions increased with age, but there was no clear difference by gender. The prevalence of the various lesions was higher in the antral mucosa than in the fundic mucosa. H. pylori infection was strikingly frequent in our study population, with prevalence rates ranging from 73% in subjects with superficial gastritis to 95% in those with atrophic gastritis and IM and 98% in those with CG. The prevalence of H. pylori was equally high in males and females, and it was significantly positively associated with the degree of infiltration of poly- and mononuclear cells and with that of active regeneration; it was inversely correlated with the degree of atrophy, IM, and dysplasia. Our findings support the precancerous nature of the various gastric lesions and the etiological role of H. pylori infection in CG.

Adult↗

PubMed1996

Idiopathic epilepsy with generalized tonic clonic seizures in Antioquia, Colombia: is the joint Amerindian and Negroid racial admixture the cause of its high prevalence?

Most Colombian populations stem from the admixture of Caucasians, Amerindians and Negroids. In the world, these two latter ethnical groups show a significantly higher prevalence of epilepsy than the former one. We tested the hypothesis that the high prevalence of idiopathic epilepsy with generalized tonic clonic seizures found in the Antioquian population (Paisas), from Colombia, is due to their possible joint Negroid and Amerindian ethnic components. We have previously demonstrated that inheritance is the principal factor for developing epilepsy in this community. Analyses of racial admixture, heterogeneity between populations, genetic distance, and phyletic relationships were performed among epileptic and non epileptic samples from the Antioquian community. Also Caucasians, Spaniards, Basques, Jews, Chileans, Negroids, Amerindians and Mongoloids were included in the analysis. Four highly polymorphic blood systems were used as genetic markers: RH, MNS, ABO and FY. They were chosen because of their high discriminant power in these ethnic groups. In the population affected with idiopathic epilepsy, the estimated Negroid and Amerindian rates of admixture were low (3% and 14%, respectively). Although, these degrees of admixture can be explained due to common ancestral origins, the estimated proportion of Amerindian admixture in the epileptic affected population, was significantly higher than the estimated for the Non affected Antioquian population. The latter finding is consistent with the analysis of heterogeneity between populations that discriminated epileptic population from non epileptic Antioquian population (p < 0.05). Epileptic and non epileptic Paisas clustered in topology with Caucasians, very close to Spaniards and Basques and highly distant from Negroids and Amerindians. Thus, far, the origin of the high prevalence of idiopathic epilepsy in the Antioquian (Paisa) population cannot be explained by the hypothetical joint Negroid and Amerindian ethnical admixture, but using additional genetic markers and other methods of racial estimation of admixture it is necessary to corroborate if the Amerindian admixture component is significantly higher in the epileptic population than in the non epileptic Paisa population.

Black People↗

PubMed1995

Determinants of plasma pepsinogen levels in a population at high risk for stomach cancer in Venezuela.

Determinants of plasma pepsinogens (PG) levels were studied in 1365 participants in a chemoprevention trial for gastric pre-cancerous lesions being conducted in Venezuela. Gastric biopsies, plasma samples and information on smoking and dietary habits were obtained at baseline examination. Both PG-I and PG-II levels increased progressively with the level of Helicobacter pylori infection in gastric biopsies, resulting in no clear trend in the I/II ratio. Instead, there was a progressive decrease in the I/II ratio with increasing degrees of infiltration of polynuclear cells and monocytes, atrophy, intestinal metaplasia and the stage of pre-cancerous lesions. The mean I/II ratios for atrophic gastritis or more advanced lesions were less than 4.0. When subjects with the I/II ratio 4 or higher were used as controls, severe reduction in the I/II ratio (< 2.0) was inversely associated with tobacco consumption. This may be due to a pharmacological effect of nicotine. The severe reduction of I/II ratio was also inversely associated with fresh fruit consumption. In addition, a decreased I/II ratio was positively associated with rice/pasta and arepas (tortilla made from corn) consumption and inversely associated with plantain consumption. Possible effects of vitamins and starchy food on the development of atrophic gastritis need to be studied further.

Adult↗

PubMed1995

Nuclear factor RIP140 modulates transcriptional activation by the estrogen receptor.

A conserved region in the hormone-dependent activation domain AF2 of nuclear receptors plays an important role in transcriptional activation. We have characterized a novel nuclear protein, RIP140, that specifically interacts in vitro with this domain of the estrogen receptor. This interaction was increased by estrogen, but not by anti-estrogens and the in vitro binding capacity of mutant receptors correlates with their ability to stimulate transcription. RIP140 also interacts with estrogen receptor in intact cells and modulates its transcriptional activity in the presence of estrogen, but not the anti-estrogen 4-hydroxytamoxifen. In view of its widespread expression in mammalian cells, RIP140 may interact with other members of the superfamily of nuclear receptors and thereby act as a potential co-activator of hormone-regulated gene transcription.

Adaptor Proteins, Signal Transducing↗

PubMed1995

Transcriptional activators differ in their responses to overexpression of TATA-box-binding protein.

We investigated how overexpression of human TATA-box-binding protein (TBP) affects the action of estrogen receptor (ER) and compared the response with that of other activators. When ER activates a simple promoter, consisting of a response element and either the collagenase or tk TATA box, TBP overexpression potentiates transcription. TBP potentiates only estrogen-induced and not basal transcription and does so independent of spacing between response element and TATA box. TBP overexpression also reduces autoinhibition by overexpressed ER, suggesting that one target of the autoinhibition may be TBP itself. Both AF-1 and AF-2 domains of ER are potentiated by TBP, and each domain binds TBP in vitro. Like ER, chimeric GAL4/VP16 and GAL4/Tat activators are also potentiated by TBP, as is the synergistic activation by ER and GAL4/VP16 on a complex promoter. Unlike ER, GAL4/Sp1 and GAL4/NF-I become less potent when TBP is overexpressed. Furthermore, synergy between ER and Sp1 or between ER and NF-I, whether these are supplied by transfected GAL4 fusions or by the endogenous genes, is inhibited by TBP overexpression. Thus, ER resembles VP16 in response to TBP overexpression and is different from Sp1 and NF-I, which predominate over ER in setting the response on complex promoters.

Animals↗

PubMed1995

Response of broiler breeders to low-protein diets. 1. Adult breeder performance.

Four hundred female and 50 male commercial strain breeders were reared separately from 1 d to 18 wk of age, with all birds receiving the same diet. At 18 wk, all pullets were weighed and the extreme weights removed from the group. The remaining hens were then randomly sorted into four treatment groups each represented by four replicate groups. Treatment involved feeding different levels of CP (16, 14, 12, and 10%), supplemented with synthetic lysine and methionine in order to maintain constant lysine and TSAA levels, respectively. Diets were isoenergetic and all birds received the same quantity of feed daily. Dietary protein had no effect on egg production (P > .05). However, breeders fed 10% CP were lighter (P < .01) in weight than birds fed 16% CP. Eggs from birds fed 10 and 12% CP were consistently smaller (P < .01), and this resulted in reduced chick weight at hatching. Low-protein diets also resulted in less nitrogen excretion. These data suggest that it is possible to reduce the CP intake of broiler breeders while maintaining intake of critical amino acids without affecting performance.

Amino Acids↗

PubMed1995

Response of broiler breeders to low-protein diets. 2. Offspring performance.

Broiler breeders were allocated at random to one of four experimental diets containing various levels of CP (16, 14, 12, or 10%), at constant methionine+cystine and lysine levels of .59 and .82%, respectively. Diets were isoenergetic and all birds received the same quantity of feed daily to 64 wk of age. Eggs from birds fed 10 and 12% CP were consistently smaller (P < .01) and in two trials involving breeders at 30 and 52 wk of age this resulted in reduced chick weight at hatching, although no lasting effect was observed on weight of offspring at 48 d. Better feed efficiency (P < .05) was observed from broilers hatched from hens fed lower CP diets. These data suggest that it is possible to reduce the CP intake of broiler breeders while maintaining intake of critical amino acids without adversely affecting offspring performance.

Animals↗

PubMed1993

Intraurethral capsaicin produces reflex activation of the striated urethral sphincter in urethane-anesthetized male rats.

The effect of intraurethral application of capsaicin on the urethral motility of urethane anesthetized rats has been investigated. The urinary bladder and the urethra were surgically disconnected, and both organs were cannulated to record variations in intraluminal pressure (cystourethrogram). Urinary bladder reflex contractions in response to intravesical infusion of saline were paralleled by activation of the external striated urethral sphincter, resulting in intraluminal pressure high frequency oscillations (IPHFO) which were recorded at the urethral level. Intraurethral capsaicin (0.2 microgram./30 microliters.), produced an immediate enhancement of the IPHFO, the amplitude of which (70 +/- 9 mm.Hg) was significantly (p < 0.01) higher as compared with that recorded before drug administration (15 +/- 3 mm.Hg). The potentiation was followed (11 of 15 rats) by a period (5 to 12 minutes) characterized by a continuous low-amplitude urethral phasic activity. Throughout this period urinary bladder motility was inhibited. A second administration of capsaicin in the same animal was ineffective, and the response was absent in rats desensitized to capsaicin (50 mg./kg., subcutaneously, 4 days before), after application of tetrodotoxin (10 micrograms.) on the pudendal nerves, or after acute (3 hours before) sectioning, as well as in rats pretreated with d-tubocurarine (d-Tc, 100 micrograms./kg. intravenously). Intraurethral injection of capsaicin (0.2 microgram./30 microliters.), performed when the urinary bladder was empty, triggered IPHFO (12 +/- 3 mm.Hg) in 5 of 6 rats. This response was unaffected by hexamethonium (20 mg./kg., intravenously) or after removal (6 hours before) of the major pelvic ganglia, while it was absent after destruction of the lumbosacral spinal cord (3 to 6 hours before), in rats acutely spinalized (T13-L1), or after sectioning of the pudendal nerves. In rats receiving intrathecal (L5-S1) capsaicin (60 micrograms., 24 hours before), the capsaicin-induced IPHFO activation was lacking. Electrical field stimulation (EFS, 0.1 Hz, 30 microseconds, 20 to 30 v) of the rat isolated external urethral sphincter (EUS), elicited d-tubocurarine and tetrodotoxin-sensitive twitch contractions, the amplitude of which was unaffected by capsaicin (1 microM.). Altogether these results suggest a physiological interaction between capsaicin-sensitive primary afferents innervating the urethra and the somatic efferent innervation to the urethral rabdosphincter. Present findings suggest the existence of a chemonociceptive urethro-urethral neural loop which, via pudendal nerves, leads to a supraspinally-mediated activation of the external urethral sphincter.

Afferent Pathways↗