Preserving the value of legacy film-based teaching files in pediatric radiology.

Senior pediatric radiologists who have spent a major portion of their careers interpreting conventional film-screen radiographic studies have collected a wealth of hard-copy teaching material that is at risk of becoming obsolete. The teaching value and usefulness of analog film teaching files can be preserved using available hardware and standard software. The final product can be made available in a high-quality digital format to students, trainees and faculty without complicated search-and-retrieval methodology. This paper describes a relatively simple and low-cost procedure to preserve and use this source of wisdom and experience. It also emphasizes the role that such a resource can play as part of a comprehensive educational program.

Enterohormonal disturbances in colorectal cancer patients.

Gastrointestinal (GI) hormonal peptides play a role in the development of gastrointestinal malignancies, and their abnormal levels may contribute to dysmotility. The aim of this study was to analyze plasma concentrations of enterohormones (motilin, ghrelin, gastrin and pancreatic polypeptide) and to verify if their abnormal levels may contribute to the severity of dyspeptic symptoms in colorectal cancer patients. The study included 60 patients with colorectal malignancies (22 men and 38 women), among them 30 individuals with colon cancers (group A) and 30 subjects with rectal tumors (group B). Fasting plasma levels of pancreatic polypeptide (PP), motilin, gastrin and ghrelin were determined by means of ELISA. The results were compared with the respective parameters of healthy volunteers. Colon cancer patients presented with significantly lower concentrations of ghrelin than the subjects with rectal tumors and healthy controls (156.8±86.7 vs. 260.2±87.6 vs. 258.4±94.2 pg/ml, p=0.02), as well as with significantly higher levels of PP (265.5±66.3 vs. 154.1±54.6 vs. 148.3±64.3 pg/ml, p=0.005). Also the levels of motilin turned out to be lower in colon cancer patients than in the subjects with rectal malignancies and healthy controls. No statistically significant intergroups differences were found in plasma levels of gastrin (388.2±98.6 vs. 475.6±88.7 vs. 428.2±91.2 pg/ml, p>0.05). Epigastric bloating was the most frequent dyspeptic symptom, reported by 63.3% and 40% of patients with colon and rectal tumors, respectively. Our findings imply that colon cancer patients may present with abnormal plasma levels of enterohormones significantly more often than individuals with rectal malignancies. Dysmotility observed in colon cancer patients may result not only from anticancer surgery, but also from abnormal release of enterohormones, induced either by neoplastic process or by changes within the autonomic nervous system.

Engaging multisector stakeholders to identify priorities for global health innovation, change and research: an engagement methodology and application to prosthetics service delivery in Cambodia.

PURPOSE: While innovation is known to catalyse solutions to global sustainable development challenges, lack of engagement from stakeholders during conceptualisation and development may influence the degree of success of implementation. METHODS AND MATERIALS: This paper presents a complete and novel engagement methodology, developed from value led business modelling approaches, for working with multi-sector stakeholders. The methodology can be used to determine barriers and facilitators to clinical practice innovations or translational research, within a country-specific context. The approach has then been applied in the Cambodian prosthetics and orthotics sector to provide a practice-based exemplar application of the framework. RESULTS: This approach seeks to ensure the suitability and sustainability of clinical practice and research programmes being implemented within a complex ecosystem. A theoretical basis, drawn from academic and business innovation sectors, has been consolidated and adapted for practical application to design, direct, and inform initiatives in low resource settings. CONCLUSIONS: The methods presented provide a way to both develop and articulate the mission, vision, and goals of any proposed change, and to effectively communicate these with stakeholders in a way that engages the personal and professional values that exist in their ecosystem. It provides a structured process through which meaningful conversations can happen, and a basis for relationship management with key stakeholders; intrinsic to enable a sustained legacy from research and development.

The engagement from stakeholders during conceptualisation and throughout development can determine the success, or not, of any implementation and scale of innovation.This paper presents a conceptual stakeholder-led engagement methodology, developed from value led business modelling approaches, for determining barriers and facilitators to translational global healthcare research in a country-specific context, in this case the Cambodian prosthetics and orthotics sector.Subsequent research and development work in this area needs to carefully manage and negotiate influencing factors identified through the application of the described methodology, to ensure initiatives (whether research or wider national development work) are sustainable and successful.

Evaluation of selected protein biomarkers of renal function in rats with an experimental model of acute cyclophosphamide-induced cystitis treated with N-acetylcysteine.

The administration of cyclophosphamide (CP) is associated with the risk of developing cystitis as well as kidney injury. The aim of the study was to verify the uroprotective effect of N-acetylcysteine (NAC), as well as the evaluation of renal function in the experimental model of acute CP-induced cystitis. Rats from group 1 received intraperitoneally only a single dose of 200 mg/kg b.w. of CP. Individuals from groups 2 and 3 additionally received a single dose of 200 mg/kg b.w. of NAC, respectively, orally (p.o.) and intraperitoneally (i.p.). After the administration of the drugs, animals were subject to individual monitoring in metabolic cages to assess 24-hour diuresis and basic vital signs, and then finally sacrificed for the purpose of collecting blood and organs for histopathological analysis. Classic renal parameters (creatinine, urea, uric acid, electrolytes) as well as new markers reflecting renal function, within the filtration-resorption range - cystatin C (CysC), renal tubular integrity - kidney injury molecule-1 (KIM-1) and the condition of the glomerular filtration barrier (nephrin) were determined in the obtained serum and urine samples. In group 1 histopathological development of cystitis was confirmed with the absence of significant pathomorphological disorders of the kidneys, and the initial results of the parameters determined were obtained. In both groups 2 and 3, a decrease of inflammatory changes in urinary bladder was observed, while there were still no morphological disturbances in kidneys. The administration of NAC in both groups 2 and 3 also resulted in a decrease of concentrations in urine and a reduction in 24-hour excretion with urine of all assessed proteins (CysC, KIM-1 and nephrin). NAC, thus exhibited a uroprotective effect, which was accompanied by a functional nephroprotective effect (more accentuated during intraperitoneal administration of this compound), manifested by the reduction of urinary excretion of proteins indicative of developing renal dysfunction.

Melatonin and serotonin effects on gastrointestinal motility.

The gastrointestinal tract represents the most important extra pineal source of melatonin. Presence of melatonin (M) suggests that this hormone is somehow involved in digestive pathophysiology. Release of GI melatonin from serotonin-rich enterochromaffin EC cells of the GI mucosa suggest close antagonistic relationship with serotonin (S) and seem to be related to periodicity of food intake. Food deprivation resulted in an increase of tissue and plasma concentrations of M. Its also act as an autocrine and paracrine hormone affecting not only epithelium and immune system but also smooth muscle of the digestive tract. Low doses M improve gastrointestinal transit and affect MMC. M reinforce MMCs cyclic pattern but inhibits spiking bowel activity. Pharmacological doses of M delay gastric emptying via mechanisms that involve CCK2 and 5HT3 receptors. M released in response to lipid infusion exerts a modulatory influence that decreases the inhibitory effects of the ileal brake on gastric emptying. On isolated bowel S induces dose dependent increase in tone and reduction in amplitude of contraction which is affected by M. M reduced the tone but not amplitude or frequency of contraction. M is a promising therapeutic agent for IBS with activities independent of its effects on sleep, anxiety or depression. Since of its unique properties M could be considered for prevention or treatment of colorectal cancer, ulcerative colitis, gastric ulcers and irritable bowel syndrome.

Effect of subdiaphragmatic vagotomy and cholinergic agents in the hypothalamic-pituitary-adrenal axis activity.

In the present study, we examined whether the vagus nerve is involved in mediating the stimulation of hypothalamic-pituitary-adrenal (HPA) axis by cholinergic muscarinic and nicotinic agonists, carbachol and nicotine. The site of HPA axis muscarinic stimulation was determined using peripheral (i.p.) and intracerebroventricular (i.c.v.) administration of carbachol, atropine sulphate (AtrS) and atropine hydrobromide (AtrBr). The i.p. carbachol-(0.5 mg/kg)-induced corticosterone response was significantly reduced by i.p. pretreatment with AtrBr (0.1 mg/kg), but was not diminished by i.c.v. AtrS (0.1 mug). The increase in corticosterone secretion induced by i.c.v. carbachol (2 microg) was totally abolished by i.c.v. pretreatment with AtrS (0.1 microg) but was not altered by i.p. AtrBr. Subdiaphragmatic vagotomy performed 2 weeks earlier substantially decreased the i.p. carbachol (0.2 mg/kg)-induced ACTH response and markedly augmented ACTH and corticosterone response to a higher dose of carbachol (0.5 mg/kg) in comparison with the responses in sham operated rats. Vagotomy abolished the stimulatory effect of i.p. nicotine in a low dose (1 mg/kg) on ACTH and corticosterone secretion; the ACTH response to higher dose (2.5 mg/kg) was considerably reduced, while corticosterone response remained unaffected. These results suggest that carbachol given i.c.v. evokes considerable corticosterone response by stimulation of central cholinergic muscarinic receptors. A major part of the i.p. carbachol-induced corticosterone secretion results from peripheral cholinergic muscarinic receptor stimulation. Subdiaphragmatic vagotomy moderately intensified the carbachol-induced ACTH and corticosterone secretion. Vagotomy significantly reduced the nicotine-induced ACTH secretion, possibly by the involvement of vagal afferents. The nicotine-induced corticosterone secretion is not exclusively regulated by circulating ACTH but by various intra-adrenal regulatory components.

Dysfunction of the autonomic nervous system activity is responsible for gastric myoelectric disturbances in the irritable bowel syndrome patients.

The pathogenesis of the irritable bowel syndrome (IBS) is still unsolved. Lately most attention has been focused on visceral hypersensitivity related to dysfunction of the autonomic nervous system (ANS). The aim of this study was to evaluate changes in the ANS activity and gastric motility in constipation-predominant IBS patients using the heart rate variability (HRV) and gastric myoelectric activity (EGG) recording. 23 patients (45+/-13 yrs) matching Manning criteria and 30 healthy volunteers (47+/-5 yrs) participated in the study. EGG and HRV in fasted and fed subjects with fasted serum catecholamine levels were measured in both groups. Fasting IBS pts showed gastric dysrrhythmia (29+/-14% vs. 11+/-7%), DP was 128.860 +/- 112.000 vs. 46.000+/- 23.200microV2, DF 2.37+/-0.8 vs. 2.9+/-0.2cpm. Feeding (300 kcal) improved dysrrhythmia to 20+/-13% vs. 8+/-5%, DP decreased to 74.500+/-57.720 vs. 165.600+/-89.000microV(2) and DF increased to 2.53+/-0.7 vs. 3.2+/-0.3cpm. In fasted and fed IBS pts SWC (channels 3-4) was about 60+/-11 vs. 84+/-8% and 68+/-14 vs. 92+/-8% respectively. In IBS pts resting HRV parameters were lower (LF - 650.3 vs. 811.6 ms2; HF - 508.8 vs. 854.6 ms2); with higher LF/HF ratio in IBS patients (1.52 vs. 1.2). The serum fasting level of adrenaline and noradrenaline in IBS pts were higher 1.28+/-0.06 vs. 0.65+/-0.05 nmol/L, and 3.54+/-1.2 vs. 2.89+/- 08 nmol/L, p<0.05 respectively. Increased sympathetic drive in IBS pts reflected by high catecholamine levels and LH/HF ratio is responsible for gastric dysrrhythmias and low DF and coupling. Meal has negligible effect on EGG parameters improvement. The ANS dysfunction observed in IBS patients is most probably responsible for disturbances in gastric myoelectric activity presented as gastric dysrrhythmias resulting in gastric emptying delay and dyspeptic symptoms.

Effect of the different doses of acrylamide on acetylocholinoesterase activity, thiol groups, malondialdehyde concentrations in hypothalamus and selected muscles of mice.

Acrylamide is a chemical compound that typically forms in starchy food products during high-temperature cooking, including frying, baking and roasting. Acrylamide is a known lethal neurotoxin. Its discovery in some cooked starchy foods in 2002 prompted concerns about the carcinogenicity of those foods. Little is known about acrylamide's influence on the peripheral nerves. In our research we measured acrylamide's influence on the acetylcholinesterase activity in hypothalamus, heart muscle, skeletal muscles of the thigh and smooth muscle of the small intestine (males, Swiss strain) in relation to the thiol groups and malondialdehyde concentration. Acrylamide was injected intraperitoneally (20 and 40 mg/kg, i.e. 0.52 and 1.04 mg per animal). The hypothalamus and muscles were taken 24, 48, and 192 h after the injection. Acetylcholinesterase activity was significantly lower (P < 0.001 to P < 0.05) in all structures. It was accompanied by the statistically significant (P < 0.001 to P < 0.05) increase in malondialdehyde concentrations in most of the studied structures time periods and ACR doses. -SH groups concentrations were significantly depleted in selected structures (P < 0.001 to P < 0.05). The AChE activity evaluation in mice muscles and hypothalamus was very important because there are many evidences that acrylamide affects directly on the peripheral nerves. Thus, it causes structural damages and physiological changes. The results obtained in the present study provide evidence for the occurrence of oxidative stress after intraperitoneal injection of acrylamide to hypothalamus, heart muscle, skeletal muscles of the thigh and smooth muscle of the small intestine.

Changes in U937 cell viability induced by stress factors - possible role of calmodulin.

Current studies were aimed to elucidate influence of magnetic field (MF) stimulation on cell viability and its effect on expression of calmodulin (CaM) and Hsp70 protein which plays a role of cell stress indicator and is a Ca2+-dependent CaM-binding protein. For the experimental model we have chosen U937 cell line exposed to chemical- and/or physical stress factors. Puromycin (PMC) was used as a chemical apoptosis inducer. Alternating (AC) (6.5rms mT, 35 Hz) magnetic field combined with 6 mT static (DC) component, or pulsed electromagnetic field (45 ± 5)mT, 50 Hz (PEMF) acted as physical stressors. Cell viability was assessed by flow cytometry, and the Western blot analysis was carried out for CaM and Hsp70 levels in cytosolic extracts of U937 cells. Cell viability in samples exposed to MF alone did not differ from sham sample, for both types of MF exposure systems. Simultaneous action of MF and PMC influenced cell viability in type of MF stimulation-dependent manner. In contrast to PEMF + PMC stimulated samples, combination of ACDCMF with PMC enhanced cell death compared to PMC control. The observed changes in cell viability were correlated with changes in level of CaM and Hsp70 proteins. Immunoblots have shown, that cytosolic content of both CaM and Hsp70 proteins was enhanced in PMC-treated sample, and further elevated for ACDCMF + PMC. For PEMF + PMC stimulated samples, level of CaM was reduced compared to PMC-treated sample. The results suggest that the changes in expression of CaM and CaM-dependent proteins might modulate effectiveness of cell death under stimulation with MF and/or cytotoxic agents.

Peripheral mechanisms of intestinal dysmotility in the morphine tolerant and dependent rats.

Changes of intestinal motility and transit produced by tolerance to and dependence upon morphine have been partly attributed to peripheral mechanisms. We evaluated the effect of chronic peripheral morphine administration and peripheral mu-receptor blockade on vagal afferent activity (VAA) and c-Kit positive intramuscular cells of Cajal (ICCs). Ten rats were subjected to chronic subcutaneous morphine infusion for 72 h with subsequent VAA recording. Potential frequency was evaluated within recordings before and after mu receptor blockade by (D)-Phe -Cys -Tyr -(D)-Trp -Orn -Thr -Phe -Thr (CTOP) i.p. injections. Afterwards the rats were sacrificed and intramuscular c-Kit antigen expression was assessed by image analysis within removed fragments of duodenum and ascending colon. An equal group of rats served as a control for VAA and c-Kit expression. Analysis of VAA revealed similar frequencies of potentials in morphine tolerant / dependent rats before CTOP and in the controls. CTOP increased potential frequency in the morphine group which effect was visible mostly within the first 20 minutes (p=0.01). The morphine infused animals presented also higher c-Kit expression in both the duodenum (p<0.001) and the ascending colon (p<0.001) in comparison to the control group. Results of our study may indicate the involvement of both the intestinal wall and the long vago-vagal reflexes in tolerance to and dependence upon opioids.

Peripheral mechanisms of intestinal dysmotility in rats with salsolinol induced experimental Parkinson's disease.

Gastrointestinal dysmotility in Parkinson's disease (PD) has been attributed in part to peripheral neurotoxine action. Our purpose was the evaluation of the salsolinol effect on intramuscular interstitial cells of Cajal (ICC), duodenal myoelectrical activity (DMA) and vagal afferent activity (VAA) in rats with experimental PD. Twenty rats were divided into 2 equal groups. Experimental PD was produced in one group by 3 weeks of the intraperitoneal salsolinol injections (50 mg/kg/day), whereas the 2-nd group served as control. DMA and VAA were recorded in both groups during fasting and stepwise--gastric distension (GD) of 10 ml. Subsequently fragments of duodenum were removed and intramuscular ICC were assessed as c-Kit antigen percentage in the duodenal muscular zone. Analyses of the fasting DMA and VAA recordings didn't reveal differences between the compared groups. During GD increase of DMA dominant frequency (p=0.04) and VAA frequency (p<0.01) was observed in the controls whereas in the salsolinol group both parameters remained unchanged. Image analysis of duodenum revealed decreased c-Kit expression in the salsolinol-injected animals (p=0.05). The results of our study may suggest the direct effect of salsolinol on both ICC and neuronal pathways of gastro-duodenal reflexes.

Prostaglandin-targeting agents and spectral heart rate variability in experimental partial bladder outlet obstruction in rats.

The purpose of this study was to determine the activity of the autonomic nervous system (ANS), using spectral analysis of the heart rate variability (HRV) in the model of partial bladder outlet obstruction (PBOO) in rats treated with selected non-steroidal anti-inflammatory drugs (NSAID): piroxicam (PRX) or meloxicam (MLX), and following administration of PGF2a prostaglandin analogue (Enzaprost F5). Neither the use of PGF2a analogue nor of MLX, caused significant changes in the HRV spectrum (except for HRV spectrum total power reduction with MLX). The use of PRX caused reduction of the total power and powers of all components of the HRV spectrum (except for VLF). Moreover, increased nLF and reduced nHF were observed. The obtained results suggest that the total prostaglandin synthesis block with a non-selective cyclooxygenase inhibitor (PRX) results in reduced ANS total activity, with decreased parasympathetic activity and a relative sympathetic predominance. The preferential cyclooxygenase-2 block (MLX) caused reduction of the total ANS activity as well, however with no clear disproportion of any part of the ANS. Therefore, prostaglandin synthesis inhibition and associated decrease of parasympathetic activity may constitute an additional and favourable feature of NSAID pharmacodynamics in the treatment of BPH.

The effects of baclofen on the feeding behaviour and body weight of vagally stimulated rats.

UNLABELLED: It is hypothesised that the GABA(B) receptor agonist baclofen increases or has no effect on food intake, and electrical stimulation of vagal nerves decreases food intake. The aim of this study was to evaluate the effects of baclofen in vagally stimulated rats. MATERIAL AND METHODS: Thirty two Wistar rats were divided into five groups: group A scheduled for microchip implantation for vagal stimulation, group B for sham operation, group C for microchip implantation and baclofen medication, group D for baclofen medication only and group E for gastric motility evaluation under influence of baclofen. The following parameters were then evaluated: food intake and body mass, gastric motility, leptin, insulin, and glucose serum levels. RESULTS: In the comparison of groups B and A, daily food intake and body weight gain decreased by 17% (p<0.05) and by 22% (p<0.05), respectively. Baclofen alone (group D) did not significantly change either food intake nor diurnal body weight compared to the controls, but when used in conjunction with the microchip (group C) it did significantly reduce effect of vagal neuromodulation (p<0.05). Furthermore, a significant decrease in leptin and glucose levels was detected in group C: 677 to 165 pg/ml (p<0.05) and 5,93 to 4,88 mmol/l (p<0.05), respectively. The administration of baclofen stimulated significantly gastric motility and elicited irregular motor migrating complex (327+/-200 against control 255+/-52 cmH2O/s). CONCLUSIONS: These results suggest that microchip vagal neuromodulation through increased vagal afferent activity induces an alteration in the feeding behaviour and decreases nocturnal food intake and body weight. These effects were partially attenuated by baclofen. The data suggests that GABA(B) receptors play an important role in the pathomechanism of attenuation of food intake induced by vagal nerve stimulation.

Loss of interstitial cells of Cajal after pulsating electromagnetic field (PEMF) in gastrointestinal tract of the rats.

Exposure to the magnetic field has remarkably increased lately due to fast urbanization and widely available magnetic field in diagnosis and treatment. However, biological effects of the magnetic field are not well recognized. The myoelectric activity recorded from the gastrointestinal and urinary systems is generated by specialized electrically active cells called interstitial cells of Cajal (ICCs). Thus it seems rational that ICC have significant vulnerability to physical factors like an electromagnetic field. The aim of this study was to evaluate the influence of pulsating electromagnetic field (PEMF) (frequency 10 kHz, 30ms, 300 muT burst, with frequency 1Hz) on ICCs density in the rat gastrointestinal tract. Rats were divided into two groups (n=32). The first group was exposed to PEMF continuously for 1, 2, 3, and 4 weeks (n = 16), and the second group (n=16) served as a control. Tissue samples of the rat stomach, duodenum and proximal colon were fixed and paraffin embedded. The tangential sections of 5 microm thickness were stained immunohistochemically with anti-c-Kit (sc-168) antibody and visualized finally by DAB as chromogen (brown end product). C-Kit positive branched ICC-like cells were detected under the light microscope, distinguished from the c-kit-negative non-branched smooth muscle cells and from the c-kit positive but non-branched mast cells and quantitatively analyzed by MultiScan computer program. Apoptosis detection was performed with rabbit anti-Bax polyclonal antibody (Calbiochem, Germany) and LSAB 2 visualization system. The surface of c-Kit immunopositive cells decreased after exposure to PEMF in each part of the gastrointestinal tract. Reduced density of ICCs was related to exposure time. The most sensitive to PEMF were ICCs in the fundus of the stomach and in the duodenum, less sensitive were ICCs in the colon and pacemaker areas of the stomach. No marked changes in ICC density in the pyloric part of the stomach were observed. We demonstrate that the PEMF induced apoptosis dependent decrease in ICC expression.

Impact of a massive waterborne cryptosporidiosis outbreak on child care facilities in metropolitan Milwaukee, Wisconsin.

OBJECTIVE: We describe the impact of the 1993 waterborne cryptosporidiosis outbreak on metropolitan Milwaukee child care homes and centers. METHODS: Information on outbreak-related illness and changes in policies and practices was collected from directors of 117 facilities. Stool specimens from 129 diapered children from 11 centers were screened for Cryptosporidium. RESULTS: Most (74%) facility directors reported children or staff with diarrhea during the outbreak; however, only 4 (3.4%) facilities closed because of illness among staff or children. During the outbreak child care homes were less likely to exclude children with diarrhea than were child care centers. Among diapered children attending centers the Cryptosporidium prevalence was 30%; 29% of infected children had no history of diarrhea associated with the Milwaukee outbreak. CONCLUSIONS: Facilities continued to operate during the outbreak despite considerable illness among children and staff. The news media were effective means for providing public health information to child care facilities. Although secondary transmission undoubtedly took place in child care facilities, the presence of children with asymptomatic Cryptosporidium infections did not result in an increased risk of diarrhea in infant and toddler rooms.

Gastrointestinal secretory, motor and circulatory effects of corticotropin releasing factor (CRF).

This study was designed to determine the effects of CRF on the gastrointestinal functions such as secretion, motility and circulation in dogs. CRF was found to inhibit dose-dependently gastric acid response to pentagastrin but not to histamine. CRF stimulated pancreatic bicarbonate and protein secretion under basal conditions and in response to secretin or cholecystokinin (CCK). This stimulation was accompanied by an increase in plasma levels of pancreatic polypeptide (PP), but not of secretin or gastrin. CRF caused a partial inhibition of the migrating motor complexes in fasted dogs and increased spike activity of the small bowel. These motor effects of CRF probably resulted from the action of the released PP on the intestinal smooth muscle. CRF is also a potent and selective stimulant of the mesenteric blood flow. This effect may be secondary to the stimulation of intestinal motility and metabolism.

Effects of nitric oxide on antral motility and gastric emptying in humans.

OBJECTIVE: It has been suggested that nitric oxide is a nonadrenergic-noncholinergic (NANC) inhibitory neurotransmitter released by the nerves in the gastrointestinal tract. We studied the influence of nitric oxide on gastric emptying and antral motility using glyceryl trinitrate (GTN), a donor of nitric oxide and L-arginine as the substrate of nitric oxide synthase. DESIGN: Six male volunteers (aged 21-24 years) participated in this placebo-controlled, double-blind study. METHODS: We investigated the effects of 0.8 mg sublingual GTN, 300 mg/kg/h intravenous L-arginine or placebo on meal-stimulated antral motility and gastric emptying on four separate occasions. After an overnight fast, a 500 ml standard liquid meal was ingested and the gastric emptying rate assessed by ultrasound. The changes in antral cross-sectional areas were measured by ultrasonography and the antral motor activity was determined simultaneously using a multilumen perfused catheter. Blood samples were taken from fasted and fed patients before and after the administration of GTN, L-arginine or placebo to determine plasma glucagon and somatostatin levels. RESULTS: GTN at a sublingual dose of 0.8 mg and 300 mg/kg/h intravenous L-arginine significantly (P < 0.01) prolonged gastric emptying half-time, averaging 56 +/- 12 and 38 +/- 8 min, respectively, compared with the placebo control value (28 +/- 7 min). The antral motor activity, calculated as the motility index (number of contractions x mmHg/min) significantly decreased in both test series, i.e., after GTN from 375.5 +/- 185.1 (control) to 104.4 +/- 55.7 (P < 0.01) and after L-arginine from 401 +/- 76 (control) to 285 +/- 57 (P < 0.05). L-arginine given intravenously at a dose of 300 mg/kg/h significantly increased plasma glucagon and somatostatin in fasted patients and increased postprandially released glucagon without affecting postprandial plasma somatostatin levels. GTN did not affect plasma hormone levels. CONCLUSIONS: Our results indicate that (1) exogenous nitric oxide inhibits gastric emptying and antral motor activity, which could be useful in the treatment of patients with functional disturbances of gastric motility and emptying; and (2) the reduction in gastric emptying and antral motility observed after the administration of L-arginine results from changes in plasma enterohormone release rather than from the enhanced formation of endogenous nitric oxide.

Encoding meal in integrated vagal afferent discharge.

Vagal afferents are integral part of the negative feedback loop induced by constitution and size of food stomach and jejunum. Aim of this study was to assess vagal discharge in response to food and gastric distension in rats. Electrophysiological recordings of vagal afferents in fasted (n=32), fed rats (n=20) and during gastric balloon distension (n=12) were performed. After 60 minutes of fasted nerve recording tube feeding was done. Fasted rats also underwent gastric distension via oesophagus. Vagal afferents discharges were analysed with dual time-amplitude window discriminator. Total vagal afferent discharge in fasted and fed rats revealed 0.3 +/- 0.12 vs 0.56 +/- 0.22 Hz (p<0.05). We observed two distinct discharge patterns: high amplitude low frequency (HALF) and low amplitude high frequency (LAHF). HALF spikes were observed more frequent in fasted than in fed rats (0.05 +/- 0.02 vs. 0.03 +/- 0.016 Hz (p<0.05). Conversely LAHF spikes in fed rats predominated over their occurrence in fasted rats: 0.52 +/- 0.2 vs. 0.25 +/- 0.12 Hz (p<0.05). Left vagal afferents discharge rises with gastric distension of 6, 8 and 10 ml and were: 0.46 +/- 0.22 Hz, 0.65 +/- 0.31 Hz, 0.86 +/- 0.33 Hz (p<0.05) respectively. Similar discharge showed right vagal afferents: 0.41 +/- 0.08 Hz, 0.51 +/- 0.13 Hz and 0.77 +/- 0.27 Hz (p<0.05) for 6, 8 and 10 ml of distension, respectively. We conclude that interdigestive information from gastrointestinal tract is encoded in high amplitude low frequency of spikes pattern in the vagus nerves.

Capasaicin induced deafferentation enhances the effect of electrical vagal nerve stimulation on food intake and body mass.

Study was based on hypothesis that electrical stimulation (ES) with parameters obtained from analysis of vagal afferent discharge fed state may fake brain with satiety state. We evaluated effect of denervation of vagal capsaicin-sensitive afferents on food intake and body weight in rats with ES of vagal nerves using microchip (MC). Group A was scheduled to MC implantation, B to sham operation only, C to MC implantation and capsaicin vagal deafferentation, and D to capsaicin denervation only. ES lasted 24 days. MC parameters were 0.05 Hz, 0.1s, 0.55 V. ES of left vagus significantly reduced total food intake as well as the mean daily intake in groups A and C in comparison to control and D group (ANOVA, F=18.55, p=0.0038). Body weight was lower in group A (3462 g) and C (2727 g) then in control (3814 g) and D (3568 g) (F=25.68, p=0.00068). Leptin decreased in C (165 pg/mL) in comparison to A (625 pg/mL), B (677 pg/mL), and D (612 pg/mL) (p<0,05), mainly due to ES (F=7.27, p=0.019). Glucose was decreased in A (F=5.55, p=0.036) - by 11% and by 16% in C group. Proper vagal neuromodulation results in central and peripheral effects causing food intake and body weight downregulation.

Nitric oxide and the interrelation between intestinal motility and pancreatic secretion in fasted and fed dogs.

Intestinal motility and pancreatic secretion show synchronous cyclic changes (MMC) that are interrupted by feeding. The aim of this study was to determine the possible implication of nitric oxide (NO) (that was proposed as nonadrenergic noncholinergic neurotransmitter) in the motor and secretory components of MMC in 5 conscious dogs equipped with monopolar electrodes implanted along the small bowel and pancreatic fistulas. In fasted dogs with typical MMCs, L-NNA (an inhibitor of NO synthase) (5 mg/kg-h i.v.) decreased the MMC interval from control value of 80 +/- 7 to 60 +/- 4 min while increasing significantly the slow waves with spikes and suppressing the phase III-related increase in pancreatic secretion. Infusion of L-arginine (L-Arg) (a substrate of NO synthase) (10 mg/kg-h i.v.) increased the MMC interval from control 79 +/- 7 to 96 +/- 8 min and reduced the slow waves spikes by about 25%. Pancreatic secretion showed significant increase to about 20%. CCK maximum. Similar but transient effects were observed when glyceryl trinitrate (GTN) (a donor of NO) (1 mg/kg-h) was administered. After ingestion of meal, the MMC cycles were replaced by irregular spike activity with an average of about 35% slow waves with spikes and pancreatic secretion rose to about 70% of CCK maximum. Infusion of L-Arg (10 mg/kg-h) reduced by about 90% the postprandial spike activity but failed to affect significantly the pancreatic secretion. Also, injection of GTN (1 mg/kg-h) reduced the spike activity but did not influence pancreatic secretion. L-NNA in fed dogs caused an initial increase in spike activity followed by phase III and about 60% inhibition of pancreatic secretion. L-NNA added to L-Arg infusion reversed in part both intestinal motility and pancreatic secretory effects of L-Arg infusion. We conclude that NO system exerts a tonic inhibitory influence on intestinal myoelectric activity by reducing the frequency of MMC pacesetter and by suppressing the postprandial activity but stimulates pancreatic secretion.