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Rectourethral reflex: description of a reflex and its clinical significance. A preliminary report.

The present communication studies the technique and clinical significance of a new reflex which I called 'rectourethral reflex'. The study comprised 29 subjects with normal anorectal and urinary functions. The procedure consisted of inflating the rectum with a balloon connected to the distal part of a catheter. The electromyographic activity of the external urethral sphincter was recorded using a concentric needle electrode inserted into the muscle. The procedure was repeated in 10 patients after muscle infiltration with Xylocaine or saline. Rectal distension evoked external urethral sphincter contraction in all the subjects. The amplitude of motor action potentials increased with increasing rectal distension. Anesthetized muscles did not respond, while saline-infiltrated muscles responded. The latency of the reflex decreased with increasing volume of rectal inflation. The reflex harmonizes the relation between defecation and micturition. It guards against involuntary micturition when the rectal detrusor is distended. Changes in amplitude and latency of the reflex may be significant in assessing rectourinary disorders. The reflex could thus be used as an investigative tool in the diagnosis of such disorders.

Adult↗

Life-time exposure to dichlorvos affects behaviour of mature rats.

Wistar rats were exposed to dichlorvos [CAS number 62737]. Doses were 1/25; 1/50; and 1/100 LD50, that is 3.88; 1.94; 1.46; and 0.97 mg kg-1 DDVP, respectively, throughout gestation (GD1-birth) and during suckling via oral dosing to the dams, and then via the same doses by gavage for the rest of their lives. The offspring were tested in an open field (OF), a multiple T-maze, and in a 'novelty-induced-grooming' test to assess behavioural competence as adults. Dose-related increases in running time and incorrect choices in the maze were observed during the first 2 weeks of a 3-week study at 9-11 weeks of age. Horizontal activity was increased, vertical activity decreased, and defecation decreased in the OF at 9-12 weeks of age; these changes were again dose-related. Sleep was also affected at 12 weeks of age. AChE activity in the brain and in blood at sacrifice was roughly 40% to 65% of control, again reflecting the doses administered. The significantly changed behavioural profile of DDVP treated rats may serve as a useful biomarker to judge functional damage of CNS properties.

Acetylcholinesterase↗

Validation and results of a questionnaire for functional bowel disease in out-patients.

BACKGROUND: The aim was to evaluate and validate a bowel disease questionnaire in patients attending an out-patient gastroenterology clinic in Greece. METHODS: This was a prospective study. Diagnosis was based on detailed clinical and laboratory evaluation. The questionnaire was tested on a pilot group of patients. Interviewer-administration technique was used. One-hundred-and-forty consecutive patients attending the out-patient clinic for the first time and fifty healthy controls selected randomly participated in the study. Reliability (kappa statistics) and validity of the questionnaire were tested. We used logistic regression models and binary recursive partitioning for assessing distinguishing ability among irritable bowel syndrome (IBS), functional dyspepsia and organic disease patients. RESULTS: Mean time for questionnaire completion was 18 min. In test-retest procedure a good agreement was obtained (kappa statistics 0.82). There were 55 patients diagnosed as having IBS, 18 with functional dyspepsia (Rome I criteria), 38 with organic disease. Location of pain was a significant distinguishing factor, patients with functional dyspepsia having no lower abdominal pain (p < 0.001). Significant factors distinguishing between IBS and functional dyspepsia were relief of pain by either antacids or defecation (19% vs 71% and 66% vs 0% respectively). Awakening from pain at night was also a factor distinguishing between IBS and organic disease groups (26% vs 61%, p < 0.01). CONCLUSIONS: This questionnaire for functional bowel disease is a valid and reliable instrument that can distinguish satisfactorily between organic and functional disease in an out-patient setting.

Abdominal Pain↗

Specification of muscle neurotransmitter sensitivity by a Paired-like homeodomain protein in Caenorhabditis elegans.

The effects of neurotransmitters depend on the receptors expressed on the target cells. In Caenorhabditis elegans, there are two types of GABA receptors that elicit opposite effects: excitatory receptors that open cation-selective channels, and inhibitory receptors that open anion-selective channels. The four non-striated enteric muscle cells required for the expulsion step of the defecation behavior are all sensitive to GABA: the sphincter muscle expresses a classical GABA-sensitive chloride channel (UNC-49) and probably relaxes in response to GABA, while the other three cells express a cation-selective channel (EXP-1) and contract. Here we show that the expression of the exp-1 gene is under the control of dsc-1, which encodes a Paired-like homeodomain protein, a class of transcription factors previously associated with the terminal differentiation of neurons in C. elegans. dsc-1 mutants have anatomically normal enteric muscles but are expulsion defective. We show that this defect is due to the lack of expression of exp-1 in the three cells that contract in response to GABA. In addition, dsc-1, but not exp-1, affects the periodicity of the behavior, revealing an unanticipated role for the enteric muscles in regulating this ultradian rhythm.

Amino Acid Sequence↗

Semaphorin 1a and semaphorin 1b are required for correct epidermal cell positioning and adhesion during morphogenesis in C. elegans.

The semaphorin family comprises secreted and transmembrane proteins involved in axon guidance and cell migration. We have isolated and characterized deletion mutants of C. elegans semaphorin 1a (Ce-sema-1a or smp-1) and semaphorin 1b (Ce-sema-1b or smp-2) genes. Both mutants exhibit defects in epidermal functions. For example, the R1.a-derived ray precursor cells frequently fail to change anterior/posterior positions completely relative to their sister tail lateral epidermal precursor cell R1.p, causing ray 1 to be formed anterior to its normal position next to ray 2. The ray cells, which normally separate from the lateral tail seam cell (SET) at the end of L4 stage, remains connected to the SET cell even in adult mutant males. The ray 1 defects are partially penetrant in each single Ce-sema-1 mutant at 20 degrees C, but are greatly enhanced in Ce-sema-1 double mutants, suggesting that Ce-Sema-1a and Ce-Sema-1b function in parallel to regulate ray 1 position. Both mutants also have defects in other aspects of epidermal functions, including head and tail epidermal morphogenesis and touch cell axon migration, whereas, smp-1 mutants alone have defects in defecation and brood size. A feature of smp-1 mutants that is shared with mutants of mab-20 (which encodes Sema-2a) is the abnormal perdurance of contacts between epidermal cells.

Amino Acid Sequence↗

A rat model of psychopathology for use in exercise science.

Exploratory behavior, defecation, urination, and a subjective psychophysical rating system were evaluated in a series of four experiments designed to assess rat psychopathology. In every case, individual rats were studied for 5-min periods in an open field consisting of 49 7.5-inch squares. We find that the open-field test can be scored in a highly objective manner (r = 0.93-0.98) by two observers. The reproducibility (r = 0.79-0.85) of the assessment using total squares traversed is not improved using any of the other parameters evaluated. Use of total squares alone was also found to be in agreement with a subjective behavioral rating procedure (r = 0.96-0.98). Fifty percent of overall variability occurs in a rat's first trial. Therefore, the average of total squares traversed on the second and third (not necessarily consecutive) days provides a reliable and objective index of a rat's emotional status. Using this criterion, we find that a random group of 30 adult, male Sprague-Dawley rats exhibit a range of psychopathologies. We propose that this method of assessment provides a rat model of emotionality which should theoretically be modifiable by experimental paradigms involving exercise and pharmacological or dietary intervention.

Animals↗

Development of a new activity-input-type ambulatory electrocardiogram and its clinical usefulness.

There are some problems with interpretation of the results of ambulatory electrocardiographic monitoring of patients with angina pectoris. To eliminate some of these difficulties, we developed a new activity-input-type ambulatory electrocardiogram which could simultaneously record the electrocardiogram and the patient's activities. Daily activities were classified into 8 levels from lying down to running or climbing a slope, in order to record them as analyzable square waves. Accuracy of the activity input to this equipment in 10 patients with effort angina was good, with 86.7% accuracy for eating and 91.7% for defecation. A comparison was made between the first and second recordings of daily activity changes in each exertional level. The numbers, mean duration and maximum duration of actions in each level were not always equal, and often changed between the two recordings. Maximum ST depression in each exertional level showed a favorable correlation of r = 0.931 (by 1.76 +/- 0.59 vs 1.77 +/- 0.66) between the first and the second recordings. The descriptions of activities recorded in patients diaries are unreliable indicators of time, because subjects check the time sometimes during, and sometimes after, the actions concerned. This equipment can easily make real-time recordings of such information, and thus provide advantages in research. When observing the pathologic condition of patients with angina pectoris and evaluating anti-anginal drug efficacy, information on the activity of each patient is important. This equipment therefore contributes to improving problems of ambulatory electrocardiographic monitoring for the patients with angina pectoris.

Adult↗

[Physicochemical and pharmacological characteristic and clinical efficacy of an anti-irritable bowel syndrome agent, polycarbophil calcium (Polyful)].

Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by abdominal pain or discomfort and abnormal defecation. Polycarbophil calcium, a water-absorbing polymer, is expected to improve stool consistency. Polycarbophil calcium decalcified under the acidic condition and then absorbed 70 times its weight of water under the neutral condition. In in situ experiments using rat jejunum and colon, polycarbophil decreased water absorption by the intestine without affecting water secretion. Polycarbophil inhibited prostaglandin E2-, 5-hydroxy-L-tryptophan- and castor oil-induced diarrhea in mice or rats. Polycarbophil calcium also inhibited sennoside-induced diarrhea in dogs. Polycarbophil increased the weight of feces in naive or low-fiber diet feeding rats. In naive dogs, polycarbophil calcium increased stool frequency, stool weight and moisture. Polycarbophil was not absorbed from the gastrointestine, not metabolized and eliminated into feces in rats and dogs. Polycarbophil calcium did not affect the absorption of coadministered drugs in dogs. In the dose-finding clinical study for IBS, polycarbophil calcium was effective both in diarrhea and constipation. In the Phase III study, polycarbophil calcium was superior to trimebutine maleate in efficacy and equal in safety. Emesis/vomiting and thirst were observed, but episodes of diarrhea or constipation by excessive action were few. Polycarbophil calcium seems promising as an anti-IBS agent.

Acrylic Resins↗

Calcium polycarbophil, a water absorbing polymer, increases bowel movement and prevents sennoside-induced diarrhea in dogs.

The effects of calcium polycarbophil (CP), a water-absorbing polymer, on bowel movement were examined in comparison with known laxatives and anti-diarrheal agents in dogs, a species that resembles humans for stool output. CP increased stool frequency, fecal water content and fecal weight in a dose-dependent manner, but did not induce diarrhea. Sennoside and carboxymethylcellulose sodium (CMC-Na) increased fecal water content and induced diarrhea at lower doses than that which enhanced stool frequency. Trimebutine decreased stool frequency, fecal weight and fecal water content, resulting in inhibition rather than stimulation of defecation. In sennoside-induced diarrhea, loperamide and CP improved stool consistency and this was accompanied by reduced fecal moisture and frequency of diarrhea. In contrast, CMC-Na aggravated stool consistency with increased fecal water content and frequency of diarrhea, and trimebutine had little noticeable effect apart from reducing fecal weight. Our results show that CP has both laxative and anti-diarrheal effects in dogs and differed from conventional laxatives and anti-diarrheal agents. CP may be a suitable agent for treatment of idiopathic constipation, secretory diarrhea and irritable bowel syndrome with alternating constipation and diarrhea and with either predominating in terms of less side effects such as diarrhea or constipation.

Acrylic Resins↗

Effects of YM905, a novel muscarinic M3-receptor antagonist, on experimental models of bowel dysfunction in vivo.

We investigated the effects of YM905 [(+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate monosuccinate], a new orally active muscarinic M3-receptor antagonist, on bowel dysfunction in vivo using experimental models that reproduce the symptoms present in irritable bowel syndrome (IBS). YM905 potently inhibited restraint stress-induced fecal pellet output in fed rats (ED50: 4.0 mg/kg) and diarrhea in fasted rats (ED50: 1.7 mg/kg), with similar potencies to the inhibition of bethanechol-, neostigmine- and nicotine-induced fecal pellet output in rats (ED50: 3.3, 7.9 and 4.5 mg/kg, respectively). YM905 also inhibited 5-hydroxytryptamine (5-HT)-, prostaglandin E2- and castor oil-induced secretory diarrhea in mice (ED50: 5.5, 14 and 6.3 mg/kg, respectively), but showed no significant effect on cholera toxin-induced intestinal secretion in mice. In addition, YM905 (3, 10 mg/kg) reversed morphine-decreased postprandial defecation in ferrets, a model of spastic constipation, whereas remosetron, a 5-HT3-receptor antagonist, was not effective. The mode of YM905 action was similar to that of darifenacin, a selective M3-receptor antagonist, with equivalent potencies. By contrast, propantheline, an antimuscarinic drug that has been used for IBS, was much less potent. These results show that YM905 ameliorates a wide spectrum of bowel dysfunctions through the blockade of M3 receptors, suggesting its therapeutic potential for treating IBS.

Animals↗

Management of functional constipation in childhood.

Functional constipation is a common condition. In the majority of cases the constipation develops as a result of a complex weave of factors including specific triggers, e.g. reduced fluid intake following a viral infection or periods of restricted access to the toilet. The passage of large painful stools perpetuates the problem when the child begins to associate pain with defecation. The management of constipation can often be a challenge in children, who initially may be reluctant to sit on the toilet. This article will discuss the contributory factors to the cause of constipation and identify the keys to successful treatment, including ensuring a holistic child-focused approach with effective initial evacuation and appropriate maintenance therapy.

Cathartics↗

[Behavioral characteristics of open-field activities in NOD mice].

The open-field test was carried out on NOD mice of both sexes between the ages of 40 to 300 days. The behavior of both sexes of mouse was observed for 3-minute periods with an interval of 20 days. The mean scores of ambulation and rearing increased at the ages of 40-80 days old, and both scores decreased more than 100 days old. The onset of overt diabetes (DM) in female mice were observed after 120 days old. After the onset of DM with great loss of body weight, the scores of ambulation and rearing were dramatically decreased. Other parameters, urination, defecation, and preening were not changed with age of both sexes. These data suggest that conspicuous weight loss with the expression of overt diabetes in NOD female mouse might correlate to decrease of the ambulation and rearing scores.

Aging↗

Population dynamics and feeding behavior of Triatoma brasiliensis and Triatoma pseudomaculata, main vectors of chagas disease in Northeastern Brazil.

Biological parameters of Triatoma brasiliensis and T. pseudomaculata that could influence the epidemiological importance of these insects as vectors of Trypanosoma cruzi were compared. The parameters studied were incubation period, interval between hatching or moulting and first feeding, number of blood meals, development time, mortality, net reproductive rate, instantaneous daily reproductive rate, time-lapse before starting feeding, duration of feeding, blood ingestion capacity, occurrence of defecation and blood ingestion velocity. Most aspects of feeding were similar for the two species, although T. pseudomaculata had a longer life cycle than T. brasiliensis producing one and two generations per year, respectively. The two species had similar instantaneous daily rates of population growth.

Animals↗

Triatoma rubrovaria (Blanchard, 1843) (Hemiptera-Reduviidae-Triatominae) IV: bionomic aspects on the vector capacity of nymphs.

Triatoma rubrovaria has become the most frequently captured triatomine species since the control of T. infestans in the state of Rio Grande do Sul (RS), Brazil. The aim of this study was to evaluate aspects of the vectorial competence of T. rubrovaria using nymphs raised in laboratory under environmental conditions of temperature and humidity and fed on mice. The average developmental period of T. rubrovaria was 180.1 days. The percentage of defecation shortly after feeding was still higher than previous studies in which samples of T. rubrovaria subjected to a slight starvation period before the blood meal were used. The obtained results support former indication that T. rubrovaria presents bionomic characteristics propitious to be a good vector of Trypanosoma cruzi to man. Therefore its domiciliary invasion process must be continuously monitored.

Animals↗

Difficulty with evacuation after spinal cord injury: colonic motility during sleep and effects of abdominal wall stimulation.

Difficulty with evacuation (DWE) is common in individuals with spinal cord injury (SCI). Numerous studies have concluded that constipation, impaction, and incontinence cause significant morbidity and, collectively, constitute an important quality-of-life issue in individuals with SCI. Colonic motor activity was assessed using a solid-state manometry probe. We report here that colonic pressure activity is depressed during sleep compared to that observed in able-bodied controls. In addition, pressure activity was decreased during sleep compared to pre-sleep and post-sleep. We suspect that this may contribute to delayed colon transit time after SCI. In addition, since contraction of the abdominal wall musculature plays a role in normal defecation, we assessed whether an abdominal belt with implanted electrodes would improve DWE. In this respect, we demonstrated that neuromuscular stimulation of the abdominal wall improves a number of indices of defecatory function, including time to first stool and total bowel care time.

Adult↗

Ascending and descending pathways of reflex straining in the dog.

The location of ascending and descending pathways of the straining reflex was studied by making bulbar cuts in dogs. Rhythmic increases, which were elicited simultaneously in nervous outflows to the diaphragm and rectus abdominis by activation of pelvic afferent fibers, were used to indicate rhythmic straining. The increases were not affected by cutting the dorsal funiculus at the bulbospinal junction, but stopped after cutting both lateral funiculi and by longitudinally cutting the roof of the central canal just caudal to the obex. The increases were impaired by unilateral section of the bulbospinal junction, but were abolished completely after successive ipsilateral hemisection of the rostral bulb. Moreover, rhythmic increases, which appeared synchronously with rhythmic straining in unit discharges recorded from the Kölliker-Fuse nucleus and neighboring structures, disappeared after the longitudinal bulbar cut. However, reflex discharges elicited in pelvic vesical and rectal branches by stimulation of corresponding pelvic afferent fibers were not reduced. These results show that the indispensable part of the ascending pathway of rhythmic straining passes through the lateral funiculus and decussates at the lower bulb, but the pathway of micturition and defecation reflexes do not cross at that level.

Afferent Pathways↗

Excitatory neurotoxic properties of pontamine sky blue make it a useful tool for examining the functions of focal brain parts.

Pontamine sky blue (PSB) is used in brain studies to mark the position of microelectrode and micropipette tips. However, few studies have been made on the effects of PSB on neurons; therefore we examined these effects. When puffed on isolated sensory ganglion cells of rats, PSB increased membrane conductance, depolarized membrane potential, and reduced the amplitude of action potentials. When dripped on frog sympathetic ganglion, much like hexamethonium, PSB decreased the amplitude of compound action potentials of the postganglionic strand. A bath application of PSB to sartorius muscle fibers that had been treated with tetrodotoxin depolarized the membrane potential and increased the frequency and amplitude of miniature end-plate potentials. All these effects were reversible. When injected into the rat's pontine part corresponding to the location of the canine pontine defecation reflex center, PSB produced repetitive colorectal contractions and irreversibly abolished them in response to anal-canal stimulation. The excitatory and blocking effects of PSB and its staining ability make it a useful tool for examining the functions of focal brain parts.

Action Potentials↗

Functional disorders of the anus and rectum: findings on defecography.

In the past decade, interest in the anorectal region and the mechanism of continence and defecation has been increasing. Subsequently, techniques to visualize the anorectum have been introduced; evacuation proctography and defecography have been used to describe the dynamic radiologic evaluation of this area. Also, developments in anorectal manometry, electromyography, and transrectal sonography have renewed interest in defecography, particularly in categorizing the functional disorders including rectocele, intussusception and prolapse, enterocele, descending perineum syndrome, dyskinetic puborectalis muscle, solitary rectal ulcer syndrome, and incontinence.

Anal Canal↗