Sexual behavior and fertility of male rats submitted to prolonged immobilization-induced stress

In order to investigate whether prolonged stress interferes with the onset of sexual behavior at puberty and with fertility at adulthood, prepubertal male Wistar rats (40 days of age) were immobilized 6 h a day for 15 days (up to early puberty) or for 60 days (until sexual maturity). Pubertal stressed rats showed a two-fold increase in the latency for the first mount (probably due to repeated aversive experience in which a change of environment was always followed by immobilization) and a 2.5-fold increase in the frequency of thrusting (indicative of enhanced sexual performance). The apparently stimulatory effect of prolonged stress on the onset of sexual behavior is discussed in terms of increased testosterone level and interference with the complex interchanges between the neurotransmitters/neuropeptides involved in the central control of male sexual activity. Adult stressed animals were mated with normal females, which became pregnant but exhibited a more than two-fold increase in both pre-implantation and post-implantation loss, probably due to a smaller rate of fertilization and/or fertilization with damaged spermatozoa.

Intestinal permeability in strongyloidiasis

The objective of the present study was to assess intestinal permeability in patients with infection caused by Strongyloides stercoralis. Twenty-six patients (16 women and 10 men), mean age 45.9, with a diagnosis of strongyloidiasis were evaluated. For comparison, 25 healthy volunteers (18 women and 7 men), mean age 44.9, without digestive disorders or intestinal parasites served as normal controls. Intestinal permeability was measured on the basis of urinary radioactivity levels during the 24 h following oral administration of chromium-labeled ethylenediaminetetraacetic acid (51Cr-EDTA) expressed as percentage of the ingested dose. The urinary excretion of 51Cr-EDTA was significantly reduced in patients with strongyloidiasis compared to controls (1.60 ± 0.74 and 3.10 ± 1.40, respectively, P = 0.0001). Intestinal permeability is diminished in strongyloidiasis. Abnormalities in mucus secretion and intestinal motility and loss of macromolecules could explain the impaired intestinal permeability.

Variations in gastric compliance induced by acute blood volume changes in anesthetized rats

The impact of acute volume imbalances on gastric volume (GV) was studied in anesthetized rats (250-300 g). After cervical and femoral vessel cannulation, a balloon catheter was positioned in the proximal stomach. The opposite end of the catheter was connected to a barostat with an electronic sensor coupled to a plethysmometer. A standard ionic solution was used to fill the balloon (about 3.0 ml) and the communicating vessel system, and to raise the reservoir liquid level 4 cm above the animals' xiphoid appendix. Due to constant barostat pressure, GV values were considered to represent the gastric compliance index. All animals were monitored for 90 min. After a basal interval, they were randomly assigned to normovolemic, hypervolemic, hypovolemic or restored protocols. Data were compared by ANOVA followed by Bonferroni's test. Mean arterial pressure (MAP), central venous pressure (CVP) and GV values did not change in normovolemic animals (N = 5). Hypervolemic animals (N = 12) were transfused at 0.5 ml/min with a suspension of red blood cells in Ringer-lactate solution with albumin (12.5 ml/kg), which reduced GV values by 11.3% (P<0.05). Hypovolemic rats (N = 12) were bled up to 10 ml/kg, a procedure that increased GV values by 15.8% (P<0.05). In the restored group (N = 12), shed blood replacement brought GV values back to basal levels in bled animals (P>0.05). MAP and CVP values increased (P<0.05) after hypervolemia but decreased (P<0.05) with hypovolemia. In conclusion, blood volume level modulates gastric compliance, turning the stomach into an adjustable reservoir, which could be part of the homeostatic process to balance blood volume.

Esophageal striated muscle contractions in patients with Chagas' disease and idiopathic achalasia

Chagas' disease causes degeneration and reduction of the number of intrinsic neurons of the esophageal myenteric plexus, with consequent absent or partial lower esophageal sphincter relaxation and loss of peristalsis in the esophageal body. The impairment of esophageal motility is seen mainly in the distal smooth muscle region. There is no study about esophageal striated muscle contractions in the disease. In 81 patients with heartburn (44 with esophagitis) taken as controls, 51 patients with Chagas' disease (21 with esophageal dilatation) and 18 patients with idiopathic achalasia (11 with esophageal dilatation) we studied the amplitude, duration and area under the curve of esophageal proximal contractions. Using the manometric method and a continuous perfusion system we measured the esophageal striated muscle contractions 2 to 3 cm below the upper esophageal sphincter after swallows of a 5-ml bolus of water. There was no significant difference in striated muscle contractions between patients with heartburn and esophagitis and patients with heartburn without esophagitis. There was also no significant difference between patients with heartburn younger or older than 50 years or between men and women or in esophageal striated muscle contractions between patients with heartburn and Chagas' disease. The esophageal proximal amplitude of contractions was lower in patients with idiopathic achalasia than in patients with heartburn. In patients with Chagas' disease there was no significant difference between patients with esophageal dilatation and patients with normal esophageal diameter. Esophageal striated muscle contractions in patients with Chagas' disease have the same amplitude and duration as seen in patients with heartburn. Patients with idiopathic achalasia have a lower amplitude of contraction than patients with heartburn.

Effect of the acupoints ST-36 (Zusanli) and SP-6 (Sanyinjiao) on intestinal myoelectric activity of Wistar rats

Despite its ancient use as a therapeutic tool to treat several ailments, acupuncture still faces the challenge of scrutiny by Western science both in terms of its efficacy and in terms of the characterization of its effects and mechanisms of actions underlying these effects. We investigated under well-controlled and carefully characterized conditions the influence of electrical stimulation of acupuncture points ST-36 (Zusanli) and SP-6 (Sanyinjiao) on the myoelectric activity of the small intestine of 38 adult male Wistar rats. Electrical recordings obtained by means of four electrodes chronically implanted in the small intestine were used to assess the effects of acupuncture (electroacupuncture stimulation set at 2 Hz, intermittent stimulation, 1 V, for 30 min). Immobilization of the animals was associated with a consistent decrease (-8 ± 7%) in the myoelectric activity of the small intestine as measured by means of the root mean square. Conversely, acupuncture was able to significantly increase (overshoot) this activity compared to baseline (+44 ± 7%). In contrast, immobilized animals subjected to sham acupuncture had only modest (nonsignificant) increases in myoelectric activity (+9 ± 6%). Using carefully controlled conditions we confirmed previous noncontrolled studies on the ability of acupuncture to alter intestinal motility. The characterization of the topographic and temporal profiles of the effects observed here represents a basis for future dissection of the physiological and pharmacological systems underlying these effects.

Functional dyspepsia: relationship between clinical subgroups and Helicobacter pylori status in Western Turkey

The etiology of functional dyspepsia is not known. The objective of the present study was to determine the characteristics of functional dyspepsia in Western Turkey. We divided 900 patients with functional dyspepsia into three subgroups according to symptoms: ulcer-like (UL), 321 (35.6%), motility disorder-like (ML), 281 (31.2%), and the combination (C) of these symptoms, 298 (33.1%). All patients were submitted to endoscopic evaluation, with two biopsies taken from the cardia and corpus, and four from the antrum of the stomach. All biopsy samples were studied for Helicobacter pylori (Hp) density, chronic inflammation, activity, intestinal metaplasia, atrophy, and the presence of lymphoid aggregates by histological examination. One antral biopsy was used for the rapid urease test. Tissue cagA status was determined by PCR from an antral biopsy specimen by a random sampling method. We also determined the serum levels of tumor necrosis factor-alpha (TNF-alpha) and gastrin by the same method. Data were analyzed statistically by the Kolmogorov-Smirnov test and by analysis of variance. Hp and cagA positivity was significantly higher in the UL subgroup than in the others. The patients in the ML subgroup had the lowest Hp and cagA positivity and Hp density. The ML subgroup also showed the lowest level of Hp-induced inflammation among all subgroups. The serum levels of TNF-alpha and gastrin did not reveal any difference between groups. Our findings show a poor association of Hp with the ML subgroup of functional dyspepsia, but a stronger association with the UL and C subgroups.

Reproductive ability of pubertal male and female rats

Ten Fisher rats 50 to 55 days of age made up the pubertal group, and ten rats 90 to 95 days of age served as the controls. The testicular and epididymal weights and volumes of the pubertal males were lower than those of the controls (P<0.001). There was also a difference in relative epididymal weight (P<0.001). The sperm of pubertal males was morphologically abnormal in 58.2% of cases, as opposed to only 3.8% in the controls (P<0.001). The mean number of spermatozoa in the control group was 11.9 × 10(6)/ml and their viability was 99.6%, while these values could not be determined for pubertal rats. Serum testosterone was higher in the pubertal animals than in the controls (2.52 ± 1.46 vs 0.92 ± 0.34 nM, P<0.01). The ovaries of control females were heavier than those of pubertal females (P<0.001) but there was no difference in their relative weights. Serum estradiol was similar in both groups (75.5 ± 12.8 vs 81.8 ± 14.7 nM, P>0.05). At the beginning of gestation, the pubertal dams weighed less than the controls (P<0.001) but following uterectomy the body weights were equal. Pubertal dams delivered fewer pups than the controls (8.1 ± 2.5 vs 10.4 ± 1.3, P<0.05). There was no difference in the body weights of their offspring or in the weights of their placentas. The results suggest that, in contrast to their female counterparts, pubertal male rats are not fully mature and have not reached complete reproductive capacity at 50-55 days of age.

Functional role of a specific ganglioside in neuronal migration and neurite outgrowth

Cell migration occurs extensively during mammalian brain development and persists in a few regions in the adult brain. Defective migratory behavior of neurons is thought to be the underlying cause of several congenital disorders. Knowledge of the dynamics and molecular mechanisms of neuronal movement could expand our understanding of the normal development of the nervous system as well as help decipher the pathogenesis of neurological developmental disorders. In our studies we have identified and characterized a specific ganglioside (9-O-acetyl GD3) localized to the membrane of neurons and glial cells that is expressed in regions of cell migration and neurite outgrowth in the developing and adult rat nervous system. In the present article we review our findings that demonstrate the functional role of this molecule in neuronal motility.

Use of erythromycin for the treatment of severe chronic constipation in children

The efficacy of erythromycin was assessed in the treatment of 14 children aged 4 to 13 years with refractory chronic constipation, and presenting megarectum and fecal impaction. A double-blind, placebo- controlled, crossover study was conducted at the Pediatric Gastroenterology Outpatient Clinic of the University Hospital. The patients were randomized to receive placebo for 4 weeks followed by erythromycin estolate, 20 mg kg-1 day-1, divided into four oral doses for another 4 weeks, or vice versa. Patient outcome was assessed according to a clinical score from 12 (most severe clinical condition) to 0 (complete recovery). At enrollment in the study and on the occasion of follow-up medical visits at two-week intervals, patient score and laxative requirements were recorded. During the first 30 days, the mean ± SD clinical score for the erythromycin group (N = 6) decreased from 8.2 ± 2.3 to 2.2 ± 1.0 while the score for the placebo group (N = 8) decreased from 7.8 ± 2.1 to 2.9 ± 2.8. During the second crossover phase, the score for patients on erythromycin ranged from 2.9 ± 2.8 to 2.4 ± 2.1 and the score for the patients on placebo worsened from 2.2 ± 1.0 to 4.3 ± 2.3. There was a significant improvement in score when patients were on erythromycin (P < 0.01). Mean laxative requirement was lower when patients ingested erythromycin (P < 0.05). No erythromycin-related side effects occurred. Erythromycin was useful in this group of severely constipated children. A larger trial is needed to fully ascertain the prokinetic efficacy of this drug as an adjunct in the treatment of severe constipation in children.

A functional study of caustic strictures of the esophagus in children

The objective of the present study was to assess esophageal motor function in 21 children (7.5 ± 2.9 years) with caustic strictures. Esophageal manometry was performed using a water-infusion system interfaced with a polygraph and displayed on a computer screen. The data were compared with those obtained from 9 healthy children. Radionuclide transit was determined by studying deglutition of a single bolus of 99mTc pertechnetate in 10 ml of water. Non-peristaltic low-amplitude and long-duration waves were the most common findings detected in patients with strictures longer than 20% of esophageal length (N = 11). Compared with the control group, these patients presented lower mean amplitude and longer mean duration of waves (24.4 ± 11.2 vs 97.9 ± 23.7 mmHg, P < 0.05, and 6.7 ± 2.4 vs 1.6 ± 0.1 s, P < 0.05, respectively). Six patients presented low-amplitude waves just below the constricted site. Ten children presented delayed esophageal transit. There was an association between dysphagia and abnormalities on manometry (P = 0.02) and between symptoms and scintigraphy data (P = 0.01). Dysphagia in caustic strictures is due to esophageal motility abnormalities, which are closely related to the scarred segment.

A spectral analysis of the myoelectric activity of the left colon in patients with schistosomiasis mansoni

The objective of the present study was to perform a spectral analysis of the electrical activity of the left colon of patients with hepatosplenic schistosomiasis. Thirty patients were studied, divided into 2 groups: group A was composed of 14 patients (9 males and 5 females) with hepatosplenic schistosomiasis and group B was composed of 16 female patients without schistosomiasis mansoni. Three pairs of electrodes were implanted in the left colon at the moment of the surgical treatment. The signals of the electric activity of the colon were captured after postoperative recovery from the ileus and fed into a computer by means of a DATAQ data collection system which identified and captured frequencies between 0.02 and 10 Hz. Data were recorded, stored and analyzed using the WINDAQ 200 software. For electrical analysis, the average voltage of the electrical wave in the three electrodes of all patients, expressed as millivolts (mV), was considered, together with the maximum and minimum values, the root mean square (RMS), the skewness, and the results of the fast Fourier transforms. The average RMS of the schistosomiasis mansoni patients was 284.007 mV. During a long period of contraction, the RMS increased in a statistically significant manner from 127.455 mV during a resting period to 748.959 mV in patients with schistosomiasis mansoni. We conclude that there were no statistically significant differences in RMS values between patients with schistosomiasis mansoni and patients without the disease during the rest period or during a long period of contraction.

Residence of liquids in the infra-junctional portion of the proximal stomach in patients with gastroesophageal reflux disease

Patients with gastroesophageal reflux disease may have disturbances of gastric motility, which could play a role in the pathophysiology of the disease. Recent studies have suggested that the gastric region just below the gastroesophageal junction may have a distinct physiological behavior. We determined whether patients with gastroesophageal reflux disease have abnormal residence of food in the infra-junctional portion of the stomach after ingesting a liquid nutrient meal. Fasted adult patients with reflux disease (N = 11) and healthy volunteers (N = 10) ingested a liquid meal (320 ml; 437 kcal) labeled with 99m technetium-phytate and their total gastric emptying half-time and regional emptying from the stomach infra-junctional region were determined. In 8 patients, episodes of postprandial acidic reflux to the esophagus were measured for 2 h using pH monitoring. There were no differences between reflux patients and controls regarding total gastric emptying time (median: 68 min; range: 39-123 min vs 65 min and 60-99 min, respectively; P > 0.50). Food residence in the infra-junctional area was similar for patients and controls: 23% (range: 20-30) vs 27% (range: 19-30%; P = 0.28) and emptying from this area paralleled total gastric emptying (Rs = 0.79; P = 0.04). There was no correlation between residence of food in the infra-junctional area and episodes of gastroesophageal reflux (Rs = 0.06; P = 0.88). We conclude that it is unlikely that regional motor disturbances involving the infra-junctional region of the stomach play a relevant role in the pathogenesis of acidic gastroesophageal reflux.

Activation of neural cholecystokinin-1 receptors induces relaxation of the isolated rat duodenum which is reduced by nitric oxide synthase inhibitors

Cholecystokinin (CCK) influences gastrointestinal motility, by acting on central and peripheral receptors. The aim of the present study was to determine whether CCK has any effect on isolated duodenum longitudinal muscle activity and to characterize the mechanisms involved. Isolated segments of the rat proximal duodenum were mounted for the recording of isometric contractions of longitudinal muscle in the presence of atropine and guanethidine. CCK-8S (EC50: 39; 95% CI: 4.1-152 nM) and cerulein (EC50: 58; 95% CI: 18-281 nM) induced a concentration-dependent and tetrodotoxin-sensitive relaxation. Nomeganitro-L-arginine (L-NOARG) reduced CCK-8S- and cerulein-induced relaxation (IC50: 5.2; 95% CI: 2.5-18 µM) in a concentration-dependent manner. The magnitude of 300 nM CCK-8S-induced relaxation was reduced by 100 µM L-NOARG from 73 ± 5.1 to 19 ± 3.5% in an L-arginine but not D-arginine preventable manner. The CCK-1 receptor antagonists proglumide, lorglumide and devazepide, but not the CCK-2 receptor antagonist L-365,260, antagonized CCK-8S-induced relaxation in a concentration-dependent manner. These findings suggest that CCK-8S and cerulein activate intrinsic nitrergic nerves acting on CCK-1 receptors in order to cause relaxation of the rat duodenum longitudinal muscle.

Primary and secondary esophageal contractions in patients with gastroesophageal reflux disease

We studied the primary and secondary esophageal peristalsis in 36 patients with heartburn and acid regurgitation and in 14 asymptomatic volunteers. Primary peristalsis was elicited by ten swallows of a 5-mL bolus of water and secondary peristalsis was elicited by intra-esophageal infusion of 5, 10, and 15 mL water, 0.1 N hydrochloric acid and air. Esophageal contractions were measured by an 8-lumen manometric catheter assembly incorporating a 6-cm sleeve device. Contractions were registered at 3, 9, and 15 cm from the upper margin of the sleeve and the infusion was done through a side hole located at 12 cm. Twenty patients had normal endoscopic esophageal examination, 10 with normal (group I) and 10 with abnormal pH-metric examination (group II), and 16 had esophagitis (group III). The amplitude of contractions after swallows was lower (97.8 ± 10.0 mmHg) in the distal esophagus of group III patients than in controls (142.3 ± 14.0 mmHg). Patients of group III had fewer secondary contractions (water: 25% of infusion) than patients of the other groups and controls (67% of infusion). Patients of group III also had a lower amplitude of secondary peristalsis in the distal esophagus (water: 70.1 ± 9.6 mmHg) than controls (129.2 ± 18.2 mmHg). We conclude that patients with esophagitis have an impairment of primary and secondary peristalsis in the distal esophagus.

Inducible nitric oxide synthase and tumor necrosis factor-alpha in delayed gastric emptying and gastrointestinal transit induced by lipopolysaccharide in mice

Gastrointestinal motility disturbances during endotoxemia are probably caused by lipopolysaccharide (LPS)-induced factors: candidates include nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), interleukin-1ß, and interleukin-6. Flow cytometry was used to determine the effects of LPS and these factors on gastric emptying (evaluated indirectly by determining percent gastric retention; %GR) and gastrointestinal transit (GIT) in male BALB/c mice (23-28 g). NO (300 µg/mouse, N = 8) and TNF-alpha (2 µg/mouse, N = 7) increased (P < 0.01) GR and delayed GIT, mimicking the effect of LPS (50 µg/mouse). During early endotoxemia (1.5 h after LPS), inhibition of inducible NO synthase (iNOS) by a selective inhibitor, 1400 W (150 µg/mouse, N = 11), but not antibody neutralization of TNF-alpha (200 µg/mouse, N = 11), reversed the increase of GR (%GR 78.8 ± 3.3 vs 47.2 ± 7.5%) and the delay of GIT (geometric center 3.7 ± 0.4 vs 5.6 ± 0.2). During late endotoxemia (8 h after LPS), both iNOS inhibition (N = 9) and TNF-alpha neutralization (N = 9) reversed the increase of GR (%GR 33.7 ± 2.0 vs 19.1 ± 2.6% (1400 W) and 20.1 ± 2.0% (anti-TNF-alpha)), but only TNF-alpha neutralization reversed the delay of GIT (geometric center 3.9 ± 0.4 vs 5.9 ± 0.2). These findings suggest that iNOS, but not TNF-alpha, is associated with delayed gastric emptying and GIT during early endotoxemia and that during late endotoxemia, both factors are associated with delayed gastric emptying, but only TNF-alpha is associated with delayed GIT.