Green synthesis and characterization of gold nanoparticles using endophytic fungi Fusarium solani and its in-vitro anticancer and biomedical applications.

The present study aimed to explore the anticancer potentials of the gold nanoparticles (NPs) obtained by green synthesis method using an endophytic strain Fusarium solani ATLOY - 8 has been isolated from the plant Chonemorpha fragrans. The formation of the NPs was analyzed by UV, FTIR, SEM and XRD. The synthesized NPs showed pink-ruby red colors and high peak plasmon band was observed between 510 and 560 nm. It is observed that intensity of absorption steadily increases the wavelength and band stabilizes at 551 nm. The XRD pattern revealed the angles at 19, 38.32, 46.16, 57.50, and 76.81° respectively. Interestingly, the FTIR band absorption noted at 1413 cm-1, 1041 cm-1 and 690 cm-1 ascribed the presence of amine II bands of protein, C-N and C-H stretching vibrations of the nanoparticles. SEM analysis indicated that the average diameter of the synthesized nanoparticles was between 40 and 45 nm. These NPs showed cytotoxicity on cervical cancer cells (He La) and against human breast cancer cells (MCF-7) and the NPs exhibited dose dependent cytotoxic effect. IC50 value was 0.8 ± 0.5 µg/mL on MCF-7 cell line and was found to be 1.3 ± 0.5 µg/mL on MCF-7 cell lines. The synthesized NPs induced apoptosis on these cancer cell lines. The accumulation of apoptotic cells decreased in sub G0 and G1 phase of cell cycle in the MCF-7 cancer cells were found to be 55.13%, 52.11% and 51.10% after 12 h exposure to different concentrations. The results altogether provide an apparent and versatile biomedical application for safer chemotherapeutic agent with little systemic toxicity.

Prevalence and impact of self-reported irritable bowel symptoms in the general population.

Background and aims: The symptom-based diagnostic criteria for irritable bowel syndrome (IBS) have recently been revised in the Rome IV consensus. On the other hand, with rising public awareness of IBS, self-diagnosis and self-management is also increasing. We compared the prevalence and impact of Rome IV-based IBS vs self-diagnosed IBS in the general population. Methods: An internet panel filled out an online survey on bowel symptoms and their impact on health care utilization and daily activities. Results: A representative internet panel of 1012 individuals completed the online survey. Bowel symptoms were present in 68.6% of the population. Of these, 21% consulted a physician for these symptoms in the last year and 42% earlier. Rome IV IBS criteria were fulfilled by 5.5%, and these were younger and more likely to be female. In this subset, 37% had consulted a physician for IBS symptoms in the preceding year and 29% had done so earlier. A colonoscopy had been performed in 22%. Based on a brief description, 17.6% of the population self-identified as suffering from IBS (p < 0.001 compared to Rome IV IBS prevalence), and these were more likely to be female. Concordance with the Rome IV criteria was only 25%, but except for a lower reporting of pain, the symptom pattern, severity, impact on daily life, inability to work and health care utilization were similar to the Rome IV group. A total of 134 days of absence from work were attributed to bowel symptoms in those self-reporting with IBS. Conclusion: In the general population, bowel symptoms are highly prevalent, and the self-reported "IBS" is three times more prevalent than according to Rome IV criteria. Self-reported IBS is associated with a similar impact on health care utilization and quality of life but a higher impact on absence from work.

The 2018 ISDE achalasia guidelines.

Achalasia is a relatively rare primary motor esophageal disorder, characterized by absence of relaxations of the lower esophageal sphincter and of peristalsis along the esophageal body. As a result, patients typically present with dysphagia, regurgitation and occasionally chest pain, pulmonary complication and malnutrition. New diagnostic methodologies and therapeutic techniques have been recently added to the armamentarium for treating achalasia. With the aim to offer clinicians and patients an up-to-date framework for making informed decisions on the management of this disease, the International Society for Diseases of the Esophagus Guidelines proposed and endorsed the Esophageal Achalasia Guidelines (I-GOAL). The guidelines were prepared according the Appraisal of Guidelines for Research and Evaluation (AGREE-REX) tool, accredited for guideline production by NICE UK. A systematic literature search was performed and the quality of evidence and the strength of recommendations were graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Given the relative rarity of this disease and the paucity of high-level evidence in the literature, this process was integrated with a three-step process of anonymous voting on each statement (DELPHI). Only statements with an approval rate >80% were accepted in the guidelines. Fifty-one experts from 11 countries and 3 representatives from patient support associations participated to the preparations of the guidelines. These guidelines deal specifically with the following achalasia issues: Diagnostic workup, Definition of the disease, Severity of presentation, Medical treatment, Botulinum Toxin injection, Pneumatic dilatation, POEM, Other endoscopic treatments, Laparoscopic myotomy, Definition of recurrence, Follow up and risk of cancer, Management of end stage achalasia, Treatment options for failure, Achalasia in children, Achalasia secondary to Chagas' disease.

Safety and efficacy of pasireotide in dumping syndrome-results from a phase 2, multicentre study.

BACKGROUND: Dumping syndrome is a prevalent complication of oesophageal and gastric surgery characterised by early (postprandial tachycardia) and late (hypoglycaemia) postprandial symptoms. AIM: To evaluate efficacy and safety of the somatostatin analogue, pasireotide in patients with dumping syndrome after bariatric or upper gastrointestinal cancer surgery. METHODS: A single-arm, open-label, multicentre, intrapatient dose-escalation, phase 2 study with 4 phases: screening, 3-month SC (subcutaneous), 3-month IM (intramuscular) and 6-month optional extension IM phase. Primary endpoint was the proportion of patients without hypoglycaemia (plasma glucose <3.3 mmol/L [60 mg/dL] during an oral glucose tolerance test, OGTT) at the end of 3-month SC phase. A ≥50% response rate was considered clinically relevant. RESULTS: Forty-three patients with late dumping were enrolled; 33 completed the 3-month SC phase and 23 completed the 12-month study. The proportion of patients without hypoglycaemia at month 3 (primary endpoint) was 60.5% (26 of 43; 95% confidence interval, 44.4%-75.0%). Improvement in quality of life was observed during SC phase, which was maintained in the IM phase. The proportion of patients with a rise in pulse rate of ≥10 beats/min during OGTT reduced from baseline (60.5%) to month 3 (18.6%) and month 12 (27.3%). Overall (month 0-12), the most frequent (>20% of patients) adverse events were headache (34.9%); diarrhoea, hypoglycaemia (27.9% each); fatigue, nausea (23.3% each); and abdominal pain (20.9%). CONCLUSION: These results suggest that pasireotide is a promising option in patients with dumping syndrome after bariatric or upper gastrointestinal cancer surgery.

Health problems associated with irritable bowel syndrome: analysis of a primary care registry.

BACKGROUND: Associations between irritable bowel syndrome and other health problems have been described, but comprehensive reports are missing, especially in primary care. AIMS: To investigate which health problems are associated with irritable bowel syndrome, how they cluster together and when they are typically diagnosed relative to irritable bowel syndrome. METHODS: We used Intego, a general practice registry in Flanders, Belgium. Patients with an irritable bowel syndrome diagnosis (n = 13 701) were matched with controls without gastrointestinal diagnosis and controls with organic gastrointestinal disease. Long-term prevalences of 680 symptoms and diagnoses were compared between patients and controls. Results were summarised using functional enrichment analysis and visualised in a network and we calculated incidence rate ratios in the 10 years before and after the irritable bowel syndrome diagnosis for the network's key components. RESULTS: Various symptoms and infections, but not neoplasms, were enriched in irritable bowel syndrome patients compared to both control groups. We characterised the comorbidities of irritable bowel syndrome as psychosocial health problems, urogenital symptoms and infections, musculoskeletal symptoms and other somatic symptoms. These had a uniform incidence in the years around the irritable bowel syndrome diagnosis, and did not structurally precede or follow irritable bowel syndrome. CONCLUSIONS: Irritable bowel syndrome shares long-term associations with psychosocial health problems, urogenital symptoms and infections, musculoskeletal symptoms and other somatic symptoms in primary care. Clinicians are encouraged to take comorbidities into account when diagnosing and managing irritable bowel syndrome, as this may have important treatment implications.

The effect of mirtazapine on gastric accommodation, gastric sensitivity to distention, and nutrient tolerance in healthy subjects.

BACKGROUND: Disturbances of gastric motor function of functional dyspepsia (FD) have been implicated in the pathogenesis of the symptoms, and hence, motility modifying agents are considered for its treatment. Mirtazapine was recently shown to improve symptoms and increase nutrient tolerance in FD patients with weight loss. We aim to evaluate the effect of mirtazapine on gastric sensorimotor function in healthy volunteers (HV). METHODS: Thirty-one HV underwent an intragastric pressure (IGP) and barostat measurements on separate days before and after 3 weeks of placebo or mirtazapine (15 mg). Gastric compliance, sensitivity and accommodation (GA) measured by the barostat. GA was quantitated as the difference (delta) in intra-balloon volume before and after ingestion of 200 mL of a nutrient drink (ND). GA measured by IGP was quantitated as the drop of IGP from baseline during the intragastric infusion of ND until maximal satiation. KEY RESULTS: Mirtazapine significantly increased the bodyweight of subjects (67.8±3.7 to 69.1±3.7 kg; P=.01). Barostat results showed no effect on gastric compliance, sensitivity, and GA. Nutrient tolerance was not affected after treatment (1170±129.4 vs 1104±133.6 kcal; P=.4), and mirtazapine was associated with lower symptom ratings. The IGP drop during meal ingestion was significantly suppressed (area under the curve: -43.3±4.5 mm Hg vs -28.9±3.1 mm Hg; P=.005). CONCLUSIONS & INFERENCES: In HVs, the occurrence of weight gain and decreased meal-induced symptoms in spite of a suppressed meal-induced IGP drop, point towards a central mode of action. Mirtazapine does not display changes in gastric sensorimotor function that could explain its beneficial effects on symptoms and nutrient tolerance in FD.

Economic evaluation of the randomized European Achalasia trial comparing pneumodilation with Laparoscopic Heller myotomy.

BACKGROUND: A recent multicenter randomized trial in achalasia patients has shown that pneumatic dilation resulted in equivalent relief of symptoms compared to laparoscopic Heller myotomy. Additionally, the cost of each treatment should be also taken in consideration. Therefore, the aim of the present study was to perform an economic analysis of the European achalasia trial. METHODS: Patients with newly diagnosed achalasia were enrolled from to 2003 to 2008 in 14 centers in five European countries and were randomly assigned to either pneumatic dilation (PD) or laparoscopic Heller (LHM). The economic analysis was performed in the three centers in three different countries where most patients were enrolled (Amsterdam [NL], Leuven, [B] and Padova [I]) and then applied to all patients included in the study. The total raw costs of the two treatments per patient include the initial costs, the costs of complications, and the costs of retreatments. RESULTS: Two hundred and one patients, 107 (57 males and 50 females, mean age 46 CI: 43-49 years) were randomized to LHM and 94 (59 males and 34 females, mean age 46 CI 43-50 years) to PD. The total cost of PD per patient was quite comparable in the three different centers; €3397 in Padova, €3259 in Amsterdam and €3792 in Leuven. For LHM, the total costs per patient were highest in Amsterdam: €4488 in Padova, €6720 in Amsterdam, and €5856 in Leuven. CONCLUSION: In conclusion, the strategy of treating achalasia starting with PD appears the most economic approach, independent of the health system.

Prevalence and impact of childhood adversities and post-traumatic stress disorder in women with fibromyalgia and chronic widespread pain.

OBJECTIVE: This study investigates the prevalence of different types of childhood adversities (CA) and posttraumatic stress disorder (PTSD) in female patients with Fibromyalgia or Chronic Widespread Pain (FM/CWP) compared to patients with Functional Dyspepsia (FD) and achalasia. In FM/CWP, we also investigated the association between CA and PTSD on the one hand and pain severity on the other. METHODS: Patient samples consisted of 154 female FM/CWP, 83 female FD and 53 female achalasia patients consecutively recruited from a tertiary care hospital. Well-validated self-report questionnaires were used to investigate CA and PTSD. RESULTS: Forty-nine per cent of FM/CWP patients reported at least 1 type of CA, compared to 39.7% of FD patients and 23.4% of achalasia patients (p < 0.01). The prevalence of CA did not differ significantly between FM/CWP and FD, but both groups had a higher prevalence of CA compared to both achalasia and healthy controls (p < 0.01). FM/CWP patients were six times more likely to report PTSD than both FD (p < 0.001) and achalasia (p < 0.001) patients. CONCLUSION: In FM/CWP, PTSD comorbidity, but not CA, was associated with self-reported pain severity and PTSD severity mediated the relationship between CA and pain severity. In summary, the prevalence of CA is higher in FM/CWP compared to achalasia, but similar to FD. However, PTSD is more prevalent in FM/CWP compared to FD and associated with higher pain intensity in FM/CWP. SIGNIFICANCE: As expected and has been shown in other functional disorders, we found elevated levels of childhood adversity in FM/CWP patients. Results of this study however suggest that the impact of childhood adversity (i.e. whether such events have led to the development of PTSD symptoms), rather than the mere presence of such adversity, is of crucial importance in FM/CWP patients. Screening for PTSD symptoms should be an essential part of the assessment process in patients suffering from FM/CWP, and both prevention and intervention efforts should take into account PTSD symptoms and their impact on pain severity and general functioning.

Severely impaired gastric accommodation is a hallmark of post-Nissen functional dyspepsia symptoms.

BACKGROUND: Laparoscopic Nissen fundoplication is a commonly performed antireflux surgery, after which reflux symptoms are well controlled, however, complications such as inability to belch or dyspeptic symptoms (mimicking those of functional dyspepsia [FD]) might occur. The aim of the study was to prospectively evaluate symptom pattern and underlying pathophysiological mechanisms in patients with post-Nissen dyspepsia. METHODS: Twenty-four patients (12 f, mean age 44.5±2.8 years) with post-Nissen dyspepsia symptoms, five patients (3 f, mean age 38.8±3.2 years) with post-Nissen dysphagia symptoms and 14 pre-fundoplication patients (3 f, mean age 42.1±2.5 years) were evaluated. Patients filled out a Rome II-based dyspepsia symptom severity score, performed a gastric emptying test, and a gastric barostat study was used to evaluate the function of the proximal stomach. KEY RESULTS: Upper abdominal bloating scores were higher in post-Nissen dyspepsia patients (P=.016) and symptoms of postprandial distress syndrome (PDS) were more present in post-Nissen dyspepsia patients compared to the other two groups (P=.07). Weight loss was significantly higher in the post-Nissen groups compared to the pre-fundoplication (P=.02). Gastric emptying rates were similar in the three groups. Gastric accommodation (GA) was significantly impaired in the post-Nissen dyspepsia group (dyspepsia -30[-86-83] vs dysphagia 163[148-203] vs pre-fundoplication 147[75-174] mL, P=.004) and the prevalence of patients with impaired GA was higher in the post-Nissen group (P=.007). Postprandial fullness was more prevalent in patients with impaired GA compared to those with normal GA (P=.01). CONCLUSIONS AND INTERFERENCES: Patients with post-Nissen dyspepsia show a symptom pattern similar to that in FD patients with PDS, and the main underlying mechanism seems to be impaired gastric accommodation to a meal.

Dumping syndrome after esophageal, gastric or bariatric surgery: pathophysiology, diagnosis, and management.

BACKGROUND: Dumping syndrome, a common complication of esophageal, gastric or bariatric surgery, includes early and late dumping symptoms. Early dumping occurs within 1 h after eating, when rapid emptying of food into the small intestine triggers rapid fluid shifts into the intestinal lumen and release of gastrointestinal hormones, resulting in gastrointestinal and vasomotor symptoms. Late dumping occurs 1-3 h after carbohydrate ingestion, caused by an incretin-driven hyperinsulinemic response resulting in hypoglycemia. Clinical recommendations are needed for the diagnosis and management of dumping syndrome. METHODS: A systematic literature review was performed through February 2016. Evidence-based medicine was used to develop diagnostic and management strategies for dumping syndrome. RESULTS: Dumping syndrome should be suspected based on concurrent presentation of multiple suggestive symptoms after upper abdominal surgery. Suspected dumping syndrome can be confirmed using symptom-based questionnaires, glycemia measurements and oral glucose tolerance tests. First-line management of dumping syndrome involves dietary modification, as well as acarbose treatment for persistent hypoglycemia. If these approaches are unsuccessful, somatostatin analogues should be considered in patients with dumping syndrome and impaired quality of life. Surgical re-intervention or continuous enteral feeding may be necessary for treatment-refractory dumping syndrome, but outcomes are variable. CONCLUSIONS: Implementation of these diagnostic and treatment recommendations may improve dumping syndrome management.

Brain responses to uncertainty about upcoming rectal discomfort in quiescent Crohn's disease - a fMRI study.

BACKGROUND: Patients with Crohn's disease (CD) in remission are exposed to chronic psychological distress, due to the constant risk of relapse. This permanent situation of anticipation and uncertainty can lead to anxiety, which may, in turn, trigger relapse. We aimed to investigate the effects of uncertainty on behavioral and brain responses to anticipation of visceral discomfort in quiescent CD patients. METHODS: Barostat-controlled rectal distensions were preceded by cued uncertain or certain anticipation in nine CD patients and nine matched healthy volunteers. Brain responses obtained before distension across the different anticipation conditions in regions of interest (ROI) involved in (anticipation of) pain were measured using functional magnetic resonance imaging and compared between CD and controls. The association between anxiety-related psychological variables and cerebral anticipatory activity was tested. KEY RESULTS: During uncertainty, CD patients had significantly stronger activations than controls in the cingulate cortex, insula, amygdala, and thalamus with trends in the hippocampus, prefrontal, and secondary somatosensory cortex. In patients, brain responses to uncertainty in the majority of ROI correlated positively with gastrointestinal symptom-specific anxiety, trait-anxiety, and intolerance of uncertainty. CONCLUSIONS & INFERENCES: In a context of uncertainty regarding occurrence of uncomfortable visceral sensations, CD is associated with excessive reactivity in brain regions known to be involved in sensory, cognitive and emotional aspects of pain processing and modulation, and threat appraisal. Our findings contribute to a better understanding of the role of emotional and cognitive processes in CD. This may, in turn, lead to the development of new (psycho)therapeutic approaches for management of symptoms and related anxiety.

Higher plasma motilin levels in obese patients decrease after Roux-en-Y gastric bypass surgery and regulate hunger.

OBJECTIVE: Motilin-induced phase III contractions of the migrating motor complex (MMC) signal hunger in healthy volunteers. The current aim was to study the role of motilin as a hunger-inducing factor in obese patients and to evaluate the effect of Roux-en-Y gastric bypass (RYGB) surgery on plasma motilin levels and hunger scores. DESIGN: Motilin and ghrelin plasma levels were determined during a complete MMC cycle in controls and obese patients selected for RYGB before, 6 months and 1 year after surgery. 20 min after the end of the second phase III, obese patients received an intravenous infusion of 40 mg erythromycin. Hunger was scored every 5 min. Hedonic hunger was assessed in obese patients with the Power of Food Scale questionnaire. RESULTS: Obesity caused a switch in the origin of phase III from antrum to duodenum. Obese patients had significantly higher motilin levels compared with controls during the MMC but tended to lack the motilin peak prior to phase III necessary to trigger hunger. Hunger scores during phase III were significantly lower in obese patients, but could be restored to control levels through the administration of a low dose of the motilin agonist, erythromycin. After RYGB surgery motilin, but not ghrelin, levels decreased in parallel with hedonic hunger scores. CONCLUSIONS: Motilin may be an important regulator involved in the pathogenesis of obesity.

Role of the clock gene Bmal1 and the gastric ghrelin-secreting cell in the circadian regulation of the ghrelin-GOAT system.

As adequate food intake is crucial to survival, organisms have evolved endogenous circadian clocks to generate optimal temporal patterns of food-related behavior and physiology. The gastric ghrelin-secreting cell is thought to be part of this network of peripheral food-entrainable oscillators (FEOs), regulating the circadian release of this orexigenic peptide. This study aimed to determine the role of the core clock gene Bmal1 and the gastric ghrelin-secreting cell as an FEO in the circadian rhythmicity of ghrelin expression and secretion in vivo and in vitro. Bmal1-deficient mice not only lacked circadian rhythmicity in plasma ghrelin levels and food intake, but also showed decreased gastric mRNA expression of ghrelin and ghrelin O-acyltransferase (GOAT), the ghrelin activating enzyme. Furthermore, in the absence of the hypothalamic master clock, food-related stimuli entrained the molecular clock of gastric ghrelinoma cells to regulate the rhythmic release of ghrelin. Divergent responses in octanoyl and total ghrelin release towards different food cues were observed, suggesting that the FEO also regulates the circadian rhythmicity of GOAT. Collectively, these findings indicate that circadian rhythmicity of ghrelin signaling requires Bmal1 and is driven by a food-responsive clock in the gastric ghrelin-secreting cell that not only regulates ghrelin, but also GOAT activity.

Chemosensory signalling pathways involved in sensing of amino acids by the ghrelin cell.

Taste receptors on enteroendocrine cells sense nutrients and transmit signals that control gut hormone release. This study aimed to investigate the amino acid (AA) sensing mechanisms of the ghrelin cell in a gastric ghrelinoma cell line, tissue segments and mice. Peptone and specific classes of amino acids stimulate ghrelin secretion in the ghrelinoma cell line. Sensing of L-Phe occurs via the CaSR, monosodium glutamate via the TAS1R1-TAS1R3 while L-Ala and peptone act via 2 different amino acid taste receptors: CaSR &TAS1R1-TAS1R3 and CaSR &GPRC6A, respectively. The stimulatory effect of peptone on ghrelin release was mimicked ex vivo in gastric but not in jejunal tissue segments, where peptone inhibited ghrelin release. The latter effect could not be blocked by receptor antagonists for CCK, GLP-1 or somatostatin. In vivo, plasma ghrelin levels were reduced both upon intragastric (peptone or L-Phe) or intravenous (L-Phe) administration, indicating that AA- sensing is not polarized and is due to inhibition of ghrelin release from the stomach or duodenum respectively. In conclusion, functional AA taste receptors regulate AA-induced ghrelin release in vitro. The effects differ between stomach and jejunum but these local nutrient sensing mechanisms are overruled in vivo by indirect mechanisms inhibiting ghrelin release.

Randomised clinical trial: transoral incisionless fundoplication vs. sham intervention to control chronic GERD.

BACKGROUND: Until recently only two therapeutic options have been available to control symptoms and the esophagitis in chronic gastro-oesophageal reflux disease (GERD), i.e. lifelong proton pump inhibitor (PPI) therapy or anti-reflux surgery. Lately, transoral incisionless fundoplication (TIF) has been developed and found to offer a therapeutic alternative for these patients. AIM: To perform a double-blind sham-controlled study in GERD patients who were chronic PPI users. METHODS: We studied patients with objectively confirmed GERD and persistent moderate to severe GERD symptoms without PPI therapy. Of 121 patients screened, we finally randomised 44 patients with 22 patients in each group. Those allocated to TIF had the TIF2 procedure completed during general anaesthesia by the EsophyX device with SerosaFuse fasteners. The sham procedure consisted of upper GI endoscopy under general anaesthesia. Neither the patient nor the assessor was aware of the patients' group affiliation. The primary effectiveness endpoint was the proportion of patients in clinical remission after 6-month follow-up. Secondary outcomes were: PPI consumption, oesophageal acid exposure, reduction in Quality of Life in Reflux and Dyspepsia and Gastrointestinal Symptom Rating Scale scores and healing of reflux esophagitis. RESULTS: The time (average days) in remission offered by the TIF2 procedure (197) was significantly longer compared to those submitted to the sham intervention (107), P < 0.001. After 6 months 13/22 (59%) of the chronic GERD patients remained in clinical remission after the active intervention. Likewise, the secondary outcome measures were all in favour of the TIF2 procedure. No safety issues were raised. CONCLUSION: Transoral incisionless fundoplication (TIF2) is effective in chronic PPI-dependent GERD patients when followed up for 6 months. Clinicaltrials.gov: CT01110811.

The impact of opioid-induced constipation among chronic pain patients with sufficient laxative use.

BACKGROUND: The impact of sufficient laxative use on opioid-induced constipation (OIC) is not known. AIM: To understand the experience and symptom burden over time among chronic non-cancer pain patients with OIC who are sufficient laxative users. METHODS: A prospective longitudinal study was conducted in United States, Canada, Germany and UK which included medical record abstraction, patient surveys and physician surveys. Patients on daily opioid therapy for ≥ 4 weeks for chronic non-cancer pain with OIC were recruited from physician offices and completed the survey at Baseline and Weeks 2, 4, 6, 8, 12, 16, 20 and 24. Sufficient laxative use was defined as at least one laxative remedy 4 or more times in the prior 2 weeks. RESULTS: Of the 489 patients who completed the Baseline survey and met OIC criteria, 234 (48%) were categorised as sufficient laxative users; 65% were female; 90% were white and 75 (32%) maintained sufficient laxative use for > 7 of the 8 follow-up periods. Patient Assessment of Constipation-Symptom (PAC-SYM) and Patient Assessment of Constipation-Quality of Life (PAC-QOL) scores indicated moderate symptom severity and impact. PAC-SYM and PAC-QOL scores remained relatively unchanged over time with a maximum score change of 0.5 points. Work productivity and activity impairment remained relatively constant. Mean per cent activity impairment because of constipation was 37% at Baseline and 34% at Week 24. CONCLUSIONS: These findings demonstrate constipation persists despite sufficient laxative use with little improvement in symptoms, HRQL or activity impairment. This ongoing burden emphasises the need to identify more efficacious constipation therapies for this chronic pain patient population.

The stomach in health and disease.

The stomach is traditionally regarded as a hollow muscular sac that initiates the second phase of digestion. Yet this simple view ignores the fact that it is the most sophisticated endocrine organ with unique physiology, biochemistry, immunology and microbiology. All ingested materials, including our nutrition, have to negotiate this organ first, and as such, the stomach is arguably the most important segment within the GI tract. The unique biological function of gastric acid secretion not only initiates the digestive process but also acts as a first line of defence against food-borne microbes. Normal gastric physiology and morphology may be disrupted by Helicobacter pylori infection, the most common chronic bacterial infection in the world and the aetiological agent for most peptic ulcers and gastric cancer. In this state-of-the-art review, the most relevant new aspects of the stomach in health and disease are addressed. Topics include gastric physiology and the role of gastric dysmotility in dyspepsia and gastroparesis; the stomach in appetite control and obesity; there is an update on the immunology of the stomach and the emerging field of the gastric microbiome. H. pylori-induced gastritis and its associated diseases including peptic ulcers and gastric cancer are addressed together with advances in diagnosis. The conclusions provide a future approach to gastric diseases underpinned by the concept that a healthy stomach is the gateway to a healthy and balanced host. This philosophy should reinforce any public health efforts designed to eradicate major gastric diseases, including stomach cancer.

Influence of a neurokinin-1 receptor antagonist (aprepitant) on gastric sensorimotor function in healthy volunteers.

BACKGROUND: Substance P (SP) is a member of the neurokinin (NK) family and is one of the established neurotransmitters in the mammalian central and enteric nervous system. It is unclear whether NK1 receptors are involved in the control of gastric sensorimotor function in man. METHODS: We studied the effects of aprepitant, an NK1 receptor antagonist used in the treatment of chemotherapy-induced emesis, on gastric sensorimotor function in healthy volunteers. Sixteen healthy volunteers (six males, 32.4 ± 2.7 years) were studied on three separate occasions after placebo, aprepitant 80 or 125 mg in randomized double-blind study to assess gastric compliance, perception to isobaric distensions, and gastric accommodation with a gastric barostat. KEY RESULTS: Compared to placebo, both doses of aprepitant did not influence gastric compliance or sensitivity to gastric distension. Aprepitant 80 and 125 mg did not have any significant effects on gastric accommodation compared with placebo (mean postprandial gastric volume increase, respectively, 83.4 ± 28.4 vs 35.3 ± 16.2 vs 83.9 ± 30.4 mL, NS). Postprandial gastric compliance and sensitivity to distention were also not altered. CONCLUSIONS & INFERENCES: In health, NK1 receptors do not appear to be involved in the control of gastric compliance, accommodation or sensitivity to distention in man.

Effect of acute peppermint oil administration on gastric sensorimotor function and nutrient tolerance in health.

BACKGROUND: Menthol reduces intestinal motility in animal studies, an effect that is probably mediated by transient receptor potential channels. Peppermint oil (PO), with menthol as a major constituent, is widely used as a spasmolytic agent in irritable bowel syndrome. In the current study, we investigated the effect of acute PO administration on intragastric pressure (IGP) profiles and gastric sensorimotor functions in health. METHODS: Healthy volunteers underwent IGP measurement before and during continuous intragastric infusion of a nutrient drink (n = 13), and gastric barostat studies (n = 13). A single capsule of PO (182 mg) or placebo was administered during the studies in a randomized controlled crossover design. Throughout the studies, healthy volunteers scored 11 epigastric symptoms on a visual analogue scale (VAS); satiation was scored on a 6-point Likert scale during intragastric infusion. KEY RESULTS: During fasting, IGP and motility index (MI) of the proximal stomach decreased significantly after PO administration compared with placebo (P < 0.0001 and <0.05, respectively). In contrast, during intragastric infusion of the nutrient drink, no significant differences were detected between PO and placebo in IGP profiles, MI, satiation scores, and epigastric symptoms. The maximum infused volume, gastric compliance or sensitivity to balloon distention did not differ between both treatment arms. However, reduced appetite scores were seen during fasting after PO treatment, as compared with placebo (P = 0.01). Postprandial VAS scores were similar between PO and placebo. CONCLUSIONS & INFERENCES: Peppermint oil reduces IGP, proximal phasic contractility, and appetite, with negligible effects on gastric sensitivity, tone, accommodation, and nutrient tolerance in health.