Spirulina Platensis Attenuates Rebound Dyspeptic Symptoms After Proton Pump Inhibitors' Discontinuation: Phase 2 Placebo-controlled Trial.

Context: Rebound acid hypersecretion after cessation of proton pump inhibitors (PPIs) can provoke dyspeptic symptoms. The search for alternatives to minimize the dyspeptic rebound symptoms after PPI discontinuation is warranted. Spirulina platensis, a dietary supplement made from blue-green algae, might be an alternative. Objective: The study intended to assess whether Spirulina platensis, through its anti-inflammatory and analgesic properties, can minimize rebound symptoms after PPI withdrawal. Design: The research team performed a randomized, phase 2, double-blinded, placebo-controlled clinical trial. Setting: The study took place at São Vicente de Paulo Hospital (trial registry number NCT04988347) in Passo Fundo, Brazil. Participants: Participants were 45 Brazilian patients in the clinical practice of two of the research team's member between November 2010 and February 2012, who were using PPIs regularly. Interventions: Participants underwent clinical and endoscopic evaluations after a 28-day run-in phase of 40 mg/day of pantoprazole. In the absence of a large hiatal hernia, peptic ulcer, or severe reflux esophagitis, participants stopped using PPIs, and the research team randomly assigned them to receive either 1.6g/day of spirulina or of a placebo for two months, followed by clinical and endoscopic reevaluations. Outcome measures: Using an intention-to-treat analysis, the primary outcomes postintervention were dyspepsia and typical reflux symptoms, either the appearance or maintenance of symptoms of >50% from baseline. Results: The median time of continuous PPI use was 32 months. The research team excluded two participants due to large hiatal hernias. Among the remaining 43 participants, 18 received spirulina (42%), and 25 used a placebo (58%). Two months later, 12 participants who had received spirulina (67%) and 18 who had received the placebo (72%) completed the study (P = .968). Rebound dyspepsia occurred in 10 out of 18 patients treated with spirulina (55.56%) and in 22 out of 25 patients treated with placebo (88%), with relative risk=0.63, CI95% (0.41-0.98), and P = .039. Reflux symptoms postintervention occurred in 72% and 76%, with the relative risk=0.95, CI95% (0.66-1.36), and P > .05, respectively. No significant side effects occurred in either group. The findings from endoscopy and gastric histology didn't differ between groups. Conclusions: A two-month course of Spirulina platensis was able to attenuate rebound dyspepsia but not reflux symptoms after PPI discontinuation. Considering its good safety profile, spirulina might be useful to relieve dyspeptic symptoms after PPI discontinuation.

Digestion-Promoting Effects and Mechanisms of Dashanzha Pill Based on Raw and Charred Crataegi Fructus.

Emerging evidence suggests that a high-fat diet (HFD) can influence endoplasmic reticulum (ER) stress and gut microbiota. Crataegi Fructus is a traditional Chinese herb widely used in formulas for dyspepsia, with Dashanzha Pill composed of raw Crataegi Fructus (DR) being a representative drug. Processing products of Crataegi Fructus, however, have a stronger pro-digestive effect, and we hypothesized that Dashanzha Pill composed of charred Crataegi Fructus (DC) is more effective. We found that the contents of glucose 1-phosphate and luteolin in DR and DC were substantially different via ultra-high performance liquid chromatography-hybrid quadrupole-Orbitrap high-resolution mass spectrometry. DC outperformed DR in improving histopathological changes, increasing gastrin and motilin, and decreasing vasoactive intestinal peptides in rats with HFD induced dyspepsia. Fecal microbiota analysis revealed that DC could restore the disturbed intestinal microbiota composition, including that of Bacteroides, Akkermansia, and Intestinimonas to normal levels. Furthermore, DC significantly reduced the mRNA and protein levels of glucose-regulated protein 78, protein kinase R-like ER kinase, and eukaryotic initiation factor 2α. Taken together, DC outperformed DR in relieving dyspepsia by regulating gut microbiota and alleviating ER stress.

Paeoniflorin Alleviates Abnormalities in Rats with Functional Dyspepsia by Stimulating the Release of Acetylcholine.

INTRODUCTION: Paeoniflorin is a main active component in traditional Chinese medicine. Paeoniae alba radix is widely used as a spasmolytic and pain-relieving agent for abdominal spasmodic pain. Functional dyspepsia (FD) is characterized by pain or burning in the epigastrium, fullness, bloating and nausea. However, limited information is available about the effect of paeoniflorin on FD. MATERIALS AND METHODS: In this study, iodoacetamide or clonidine-induced FD rat models were established to investigate the impacts of paeoniflorin on FD induced by different pathophysiologic disturbances. RESULTS: We found the therapeutic effect of paeoniflorin through assessing the gastric emptying, gastric accommodation and visceral hypersensitivity. This function of paeoniflorin was related to the release of acetylcholine (ACh), which was accompanied by reduced acetylcholinesterase (AchE) activity in stomach and hypothalamus. Paeoniflorin administration inhibited the cyclo-oxygenase-2 (COX-2) expression and increased the level of ghrelin in the stomach. Besides, the levels of occludin and ZO-1 were elevated in the duodenum from paeoniflorin-treated rats, suggesting the impaired duodenal barrier was ameliorated. DISCUSSION: These results indicate that paeoniflorin possesses the ability to alleviate functional dyspepsia.

Electroacupuncture Ameliorates Gastric Hypersensitivity via Adrenergic Pathway in a Rat Model of Functional Dyspepsia.

OBJECTIVE: Electroacupuncture (EA) is effective in treating visceral pain associated with functional dyspepsia (FD). The aim of this study was to explore the effect of chronic EA (CEA) on gastric hypersensitivity and the involvement of sympathetic nervous system in a rodent model of FD. MATERIALS AND METHODS: Gastric hypersensitivity in adulthood was induced by iodoacetamide (IA) in neonatal rats. The IA-treated rats were randomized to receive no treatment (control), sham-CEA, CEA, or adrenergic antagonists, for one week. Gastric sensitivity to graded gastric distensions was then assessed by electromyogram (EMG) analysis. Autonomic functions were assessed from the spectral analysis of heart rate variability (HRV) to derive the low-frequency (LF, sympathetic activity) and high-frequency (HF, mainly vagal activity) components expressed as percentage of total spectral power. Blood was collected for the measurement of corticosterone (CORT) and norepinephrine (NE). RESULTS: 1) CEA, but not sham-CEA, reduced the EMG response to graded gastric distension in IA-treated control rats at 40 mmHg (128 ± 6% vs. 171 ± 15%, p = 0.009), 60 mmHg (204 ± 14% vs. 271 ± 24%, p = 0.010) and 80 mmHg (269 ± 19% vs. 364 ± 33%, p = 0.025), respectively. 2) CEA, but not sham CEA, increased HF component (0.61 ± 0.02 vs. 0.46 ± 0.04 in IA-treated rats, p = 0.003) and decreased LF component (0.39 ± 0.02 vs. 0.54 ± 0.04, p = 0.003). 3) Adrenergic antagonists reduced the EMG response to graded gastric distension. 4) CEA significantly reduced plasma CORT and NE in IA-treated rats. CONCLUSIONS: EA ameliorates gastric hypersensitivity in IA-treated rats and the effect may be related to the improved sympathovagal balance and the decrease of stress hormones.

D-methionine improves cisplatin-induced anorexia and dyspepsia syndrome by attenuating intestinal tryptophan hydroxylase 1 activity and increasing plasma leptin concentration.

BACKGROUND: Cisplatin is a widely used antineoplastic drug. However, cisplatin-induced dyspepsia syndromes, including delayed gastric emptying, gastric distension, early satiety, nausea, and vomiting, often force patients to take doses lower than those prescribed or even refuse treatment. D-methionine has an appetite-enhancing effect and alleviates weight loss during cisplatin treatment. METHODS: This work established a model of anorexia and dyspepsia symptoms with intraperitoneal injection of cisplatin (5 mg/kg) once a week for three cycles. Presupplementation with or without D-methionine (300 mg/kg) was performed. Orexigenic and anorexigenic hormones (ghrelin, leptin, and glucagon-like peptide-1), tryptophan hydroxylase 1 (TPH1), 5-hydroxytryptamine receptors (5-HT2C and 5-HT3 ), and hypothalamic feeding-related peptides were measured by immunohistochemistry staining, enzyme-linked immunosorbent assay, and real-time PCR assay. KEY RESULTS: Cisplatin administration caused marked decrease in appetite and body weight, promoted adipose and fat tissue atrophy, and delayed gastric emptying and gastric distension, and D-methionine preadministration prior to cisplatin administration significantly ameliorated these side effects. Besides, cisplatin induced an evident increase in serum ghrelin level, TPH1 activity, and 5-HT3 receptor expression in the intestine and decreased plasma leptin levels and gastric ghrelin mRNA gene expression levels. D-methionine supplementation recovered these changes. The expression of orexigenic neuropeptide Y/agouti-related peptide and anorexigenic cocaine- and amphetamine-regulated transcript proopiomelanocortin neurons were altered by D-methionine supplementation in cisplatin-induced anorexia rats. CONCLUSIONS AND INFERENCES: D-methionine supplementation prevents cisplatin-induced anorexia and dyspepsia syndrome possibly by attenuating intestinal tryptophan hydroxylase 1 activity and increasing plasma leptin concentration. Therefore, D-methionine can be used as an adjuvant therapy for treating cisplatin-induced adverse effects.

Banha-sasim-tang improves gastrointestinal function in loperamide-induced functional dyspepsia mouse model.

ETHNOPHARMACOLOGICAL RELEVANCE: Banha-sasim-tang (BST; Hange-shashin-to in Kampo medicine; Banxia xiexin tang in traditional Chinese medicine) is a traditional Chinese harbal medicine that has been commonly used for gastrointestinal disorders. AIM OF THE STUDY: To investigate the pharmacological effects of BST, a standardized herbal drug, on main symptoms of functional dyspepsia including delayed gastric emptying, and underlying mechanisms of action in mouse model. METHODS AND MATERIALS: Balb/C mice were pretreated with BST (25, 50, 100 mg/kg, po) or mosapride (3 mg/kg, po) for 3 days, and then treated with loperamide (10 mg/kg, ip) after 19 h fasting. A solution of 0.05% phenol red (500 µL) or 5% charcoal diet (200 µL) was orally administered, followed by scarifying and assessment of gastric emptying or gastro-intestinal motility. C-kit (immunofluorescence), nNOS (western blot) and gastric contraction-related gene expression were examined in stomach tissue. RESULTS: The loperamide injection substantially delayed gastric emptying, while the BST pretreatment significantly attenuated this peristaltic dysfunction, as evidenced by the quantity of stomach-retained phenol red (p < 0.05 or 0.01) and stomach weight (p < 0.05 or 0.01). The BST pretreatment significantly tempered the loperamide-induced inactivation of c-kit and nNOS (p < 0.05 or 0.01) as well as the contraction-related gene expression, such as the 5HT4 receptor (5HT4R), anoctamin-1 (ANO1), ryanodine receptor 3 (RYR3) and smooth muscle myosin light chain kinase (smMLCK). The BST pretreatment also significantly attenuated the alterations in gastro-intestinal motility (p < 0.01). CONCLUSION: Our results are the first evidence of the prokinetic agent effects of Banha-sasim-tang in a loperamide-induced FD animal model. The underlying mechanisms of action may involve the modulation of peristalsis via activation of the interstitial cells of Cajal and the smooth muscle cells in the stomach.

Ameliorating effects and mechanisms of chronic electroacupuncture at ST36 in a rodent model of dyspepsia induced by cisplatin.

BACKGROUND: Chemotherapy-associated dyspepsia syndrome (CADS) is among the most intensive side effects and critical concerns for patients with cancer. To investigate the effects and mechanisms of chronic electroacupuncture (EA) at ST36 on chemotherapy-associated dyspeptic symptoms (CADS) in rats. METHODS: Cisplatin (8 mg/kg, ip) was given once to establish CADS model. EA or sham-EA treatment was then performed one hour daily for 21 days. KEY RESULTS: (a) EA treatment decreased kaolin intake within 24 hours (1.67 ± 0.23 g vs 2.36 ± 0.37 g in sham-EA, P < 0.05); EA increased food intake (9.43 ± 2.28 vs 4.32 ± 1.26 in sham-EA, P < 0.05) and cisplatin-induced reduction of body weight (426.38 ± 13.25 vs 407.92 ± 13.26 in sham-EA, P = 0.05). (b) The incidence of normal behavioral satiety sequence (53%) in EA group was greater than that in sham-EA (32%) group (X2  = 17.68, P < 0.01). (c) EA increased the percentage of normal gastric slow waves (82.6 ± 5.98 vs 22.8 ± 1.90 in sham-EA, P < 0.05). (d) EA normalized cisplatin delayed gastric emptying (71.3% ± 6.8% vs 44.6% ± 11.2% in control, P < 0.05). (e) EA decreased ratio of heart rate variability (0.30 ± 0.03 vs 0.56 ± 0.05 in sham-EA, P < 0.05). (f) EA decreased fasting ghrelin, glucagon-like peptide-1 and peptide YY (P < 0.01 vs sham-EA for all). CONCLUSIONS AND INFERENCES: Chronic EA ameliorates dyspepsia symptom and improves gastric dysmotility induced by Cisplatin, mediated via the vagal and gastrointestinal hormonal mechanisms.

Inhibitory Effects and Mechanisms of Electroacupuncture via Chronically Implanted Electrodes on Stress-Induced Gastric Hypersensitivity in Rats With Neonatal Treatment of Iodoacetamide.

BACKGROUND: Stress is considered an independent factor causing and aggravating gastrointestinal symptoms, including visceral pain. The aim of this study was to investigate effects and mechanisms of electroacupuncture (EA) on stress-induced gastric hypersensitivity in rats treated with neonatal iodoacetamide mimicking human functional dyspepsia (FD). METHODS: Neonatal rats were treated with gavage of 0.2 mL of 0.1% iodoacetamide in 2% sucrose daily for six days starting on tenth day after birth. The control group was given 0.2 mL of 2% sucrose. When the rats were eight weeks old, acute restraint stress was performed on them for 90 min. EA at ST36 (ZuSanLi) was performed during the acute stress or 30 min after the stress. Adrenoceptor blocking drugs (propranolol and phentolamine) were injected intraperitoneally 30 min before acute restraint stress to explore possible sympathetic mechanisms. Visceral-motor responses to gastric distention were assessed by electromyogram (EMG). RESULTS: 1) Stress-induced gastric hypersensitivity was significantly more severe in the FD rats, compared to the control rats. It was blocked by the adrenoceptor antagonists. 2) EA inhibited stress-induced gastric hypersensitivity; the preventive effect of EA (given during stress) was more remarkable than the curative effect (given after stress). Stress resulted in a higher sympathovagal ratio and this was suppressed by EA. CONCLUSIONS: Rats treated with neonatal iodoacetamide mimicking FD are more vulnerable to stress. Stress-induced gastric hypersensitivity can be prevented or suppressed by EA at ST36 via the restoration of sympathovagal balance.

Proton-Pump Inhibitors Reduce Gastrointestinal Events Regardless of Aspirin Dose in Patients Requiring Dual Antiplatelet Therapy.

BACKGROUND: The COGENT (Clopidogrel and the Optimization of Gastrointestinal Events Trial) showed that proton-pump inhibitors (PPIs) safely reduced rates of gastrointestinal (GI) events in patients requiring dual antiplatelet therapy (DAPT). However, utilization of appropriate prophylactic PPI therapy remains suboptimal, especially with low-dose aspirin. OBJECTIVES: The authors investigated the safety and efficacy of PPI therapy in patients receiving DAPT in low- and high-dose aspirin subsets. METHODS: Randomized patients with available aspirin dosing information in COGENT (N = 3,752) were divided into "low-dose" (≤ 100 mg) and "high-dose" (>100 mg) aspirin groups. The primary GI and cardiovascular endpoints were composite upper GI events and major adverse cardiac events, respectively. All events were adjudicated by independent, blinded gastroenterologists and cardiologists. RESULTS: Median duration of follow-up was 110 days. Low-dose aspirin users (n = 2,480; 66.1%) were more likely to be older, female, and have higher rates of peripheral artery disease, prior stroke, and hypertension, whereas high-dose aspirin users (n = 1,272; 33.9%) had higher rates of hyperlipidemia, smoking, a history of percutaneous coronary intervention, and were more than twice as likely to be enrolled from sites within the United States (80.4% vs. 39.8%). High-dose aspirin was associated with similar 180-day Kaplan-Meier estimates of adjudicated composite GI events (1.7% vs. 2.1%; adjusted hazard ratio: 0.88; 95% confidence interval: 0.46 to 1.66) and major adverse cardiac events (4.8% vs. 5.5%; adjusted hazard ratio: 0.73; 95% confidence interval: 0.48 to 1.11) compared with low-dose aspirin. Randomization to PPI therapy reduced 180-day Kaplan-Meier estimates of the primary GI endpoint in low-dose (1.2% vs. 3.1%) and high-dose aspirin subsets (0.9% vs. 2.6%; p for interaction = 0.80), and did not adversely affect the primary cardiovascular endpoint in either group. CONCLUSIONS: Gastroprotection with PPI therapy should be utilized in appropriately selected patients with coronary artery disease requiring DAPT, even if the patients are on low-dose aspirin. (Clopidogrel and the Optimization of Gastrointestinal Events Trial [COGENT]; NCT00557921).

Clinical effects of the new phosphorus binder, bixalomer in hemodialysis patients switched from sevelamer hydrochloride.

It has been reported that sevelamer hydrochloride, which is often used as a polymer phosphorus (P) binder for managing serum P concentration in dialysis patients, causes gastrointestinal adverse effects such as constipation, etc. The reason for this is thought to be that sevelamer hydrochloride has high water absorption, causing it to absorb water and swell in the gastrointestinal tract. In June 2012, the new polymer P binder bixalomer was launched in Japan. Since bixalomer has low swelling due to water absorption, it can be expected to alleviate adverse effects in the gastrointestinal system. In our study, for 21 cases of maintenance hemodialysis patients undergoing treatment with sevelamer hydrochloride at our hospital, the P binder was switched from sevelamer hydrochloride to the same dosage of bixalomer, and the concentrations of serum P, corrected calcium (Ca) and whole parathyroid hormone (PTH) before and one month after the switch were compared. In addition, gastrointestinal symptoms (acid reflux, abdominal pain, indigestion, diarrhea and constipation) were evaluated before and after the switch using a questionnaire based on the Japanese version of the Gastrointestinal Symptom Rating Scale (GSRS). By switching to bixalomer, serum P concentration was significantly reduced (P=0.024), but there were no significant changes observed for serum corrected Ca and whole PTH. Furthermore, there were no significant changes observed for all five of the evaluation items of the GSRS, before and after the switch. These results suggest that although bixalomer can more potently reduce the serum P concentration than sevelamer hydrochloride, there were no significant differences in the effects of both P binders on the gastrointestinal symptoms.

Calcium and fat metabolic balance, and gastrointestinal tolerance in term infants fed milk-based formulas with and without palm olein and palm kernel oils: a randomized blinded crossover study.

BACKGROUND: Effects of palm olein (POL) on calcium and fat metabolic balance and gastrointestinal (GI) tolerance have been clinically evaluated but its use in combination with palm kernel oil (PKO), and canola oil has not been similarly assessed in infants. METHODS: Calcium and fat balance and GI tolerance were evaluated in 33 healthy term infants (age = 68-159 d) in a randomized, double-blinded, 14 d crossover trial at a day care center in Salvador, Brazil; followed by a 4d hospital ward metabolic balance study in 17 of the male subjects. The study compared two commercially available milk-based powdered formulas in Brazil; one containing POL (44% of total fat), PKO (21.7%) and canola oil (18.5%) as predominant fats (PALM), and the other containing none (NoPALM). Occasional human milk (HM) supplementation was allowed at home. RESULTS: Formula and HM intakes, and growth were not different (p > 0.05). Calcium absorption (%) for infants fed NoPALM (58.8 ± 16.7%; means ± SD) was higher (p = 0.023) than those fed PALM (42.1 ± 19.2%), but was not significant (p = 0.104) when calcium intake was used as a covariate. Calcium intake was higher (p < 0.001) in NoPALM versus PALM fed infants. However, calcium retention (%) was higher in infants fed NoPALM compared to PALM with (p = 0.024) or without (p = 0.015) calcium intake as a covariate. Fat absorption (%) for NoPALM was greater than PALM fed infants (NoPALM = 96.9 ± 1.2 > PALM = 95.1 ± 1.5; p = 0.020 in Study Period I). Mean rank stool consistency was softer in infants fed NoPALM versus PALM (p < 0.001; metabolic period). Adverse events, spit-up/vomit, fussiness and gassiness were not different (p > 0.05). Formula acceptability was high and comparable for both formula feedings, regardless of HM supplementation. CONCLUSIONS: Term infants fed PALM based formula (containing palm olein, palm kernel and canola oils) demonstrated lower calcium retention and fat absorption, and less softer stool consistency versus infants fed NoPALM based formula. Study suggested formula fat differences may affect GI function in infants.

Gut peptide profile and chemotherapy-associated dyspepsia syndrome in patients with breast cancer undergoing FEC60 chemotherapy.

AIM: The association of motilin, ghrelin, leptin, gastrin, pepsinogen (PG) I and II with cancer chemotherapy-associated dyspepsia syndrome (CADS) was investigated in 35 patients with breast cancer receiving first cycle of 5-fluorouracil, cyclophosphamide, epirubicin (FEC60) chemotherapy. PATIENTS AND METHODS: The onset of dyspeptic symptoms on days 3 and 10 after chemotherapy identified patients with and without CADS. Gastrointestinal symptoms were scored with the Gastrointestinal Symptom Scoring Rate (GSRS) questionnaire. Gastrointestinal peptides were evaluated by enzyme-linked immunosorbent assay. RESULTS: Twenty-one patients (60%) had CADS. The area under the curve (AUC) of ghrelin was higher, whereas that of PGI, PGII and motilin were lower in patients with CADS compared to those without. In patients with CADS, the AUC of PGI and PGII negatively correlated with the GSRS indigestion cluster. CONCLUSION: Impairment of gastrointestinal motility suggested by low motilin concentrations and mucosal damage mirrored by an increase of ghrelin seem to be involved in the onset of CADS in patients during chemotherapy for breast cancer.

Zhizhu decoction promotes gastric emptying and protects the gastric mucosa.

The aim of this study was to evaluate the effects of the Zhizhu decoction on gastric emptying and gastric mucosal protection. The Zhizhu decoction is composed of Aurantii fructus and Atractylodes macrocephala Rhizoma. Results showed that oral administration of the Zhizhu decoction accelerated gastric emptying in mouse and protected gastric mucosa from ethanol-induced ulcers in rat. Our investigations demonstrated that the Zhizhu decoction accelerated gastric emptying, at least in part, by activating the muscarinic and 5-HT3 receptors. The gastroprotective effect is involved in its antioxidant effects and increased vascular endothelial growth factor expression.

[Fructooligo- and fructopoly-saccharides in correction and prevention of intestinal microbiocenosis disorders in patients with bronchopulmonary pathology receiving antibacterial therapy].

AIM: To evaluate the clinical efficacy BUD "Stimbifid (LLC In-MIN"/LLC ("MedStar", Russia), which contains inulin, oligofructose, vitamins (C, B1, B6, B12, E, PP, folic acid, pantothenic acid, biotin) and minerals (zinc, selenium) in the correction and prevention of violations of the microbiota in patients with chronic and acute diseases of the lungs in the background and after antibiotic therapy (ABT). Was examined total of 50 patients with bronchopulmonary pathology on the background and after antibiotic therapy (including 30 people at a "Stimbifid" reception). The criteria for evaluating the effectiveness were: the dynamics of clinical symptoms, while in transit through the intestines of activated carbon ("carbolex test"), bacteriological examination of feces before and after treatment, the definition of short-chain fatty acids in the faeces before and after treatment. Based on the results of complex research was established the high efficiency of "Stimbifida" in the correction of microbiota in patients with chronic and acute diseases of the lungs in the background and after antibiotic therapy.

[Dyspeptic syndrome associated with antidiabetic therapy]. / Dyspeptický syndrom pri antidiabetické lécbe.

Dyspeptic syndrome is a common complication of treatment with antidiabetic drugs. This may be a trivial as well as a very serious complication. Nausea, vomiting, diarrhoea, abdominal pain, loss of appetite and taste disturbances are the most common symptoms of dyspeptic problems in patients treated with metformin. They rarely are a reason for treatment discontinuation. Dyspeptic syndrome is a common complication in patients treated with acarbose, this may be prevented by reduced intake of sucrose. Pneumatosis cystoides intestinalis is a rare complication in acarbose-treated patients. Antiobesity agent orlistat is frequently associated with dyspeptic symptoms, particularly if fat intake is not reduced. Treatment with drugs affecting the incretin system (dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists) is very rarely complicated by acute pancreatitis. Glucagon-like peptide-1 receptor agonists may cause dyspeptic symptoms (nausea, vomiting, diarrhoea) at the beginning of treatment. These complaints usually cease and the treatment usually does not need to be discontinued.

[Use of Legalon in non-alcoholic fatty liver disease].

The article presents the current understanding of the etiology, pathogenesis of nonalcoholic fatty liver disease, its basic forms, risk factors, prevalence and clinical course. Shows the data of research on the effectiveness of purely herbal product Legalon, in the treatment of non-alcoholic fatty liver disease. The 2-month course of treatment was underwent in the research team, on that background there was noted positive dynamics: cropped asthenic syndrome, pain and heaviness in the right hypochondrium, dyspepsia. In assessing of the biochemical parameters was shown a significant decrease in serum transaminases, gamma-glyutamiltransaminazy level.

[Phosphorus binders: preferences of patients on haemodialysis and its impact on treatment compliance and phosphorus control]. / Captores del fósforo: preferencias de los pacientes en hemodiálisis y su repercusión sobre el cumplimiento del tratamiento y el control del fósforo.

INTRODUCTION: Non-adherence to phosphate binding (PB) medication may play a role in the difficulty in achieving the targets for phosphorus. We have a wide armamentarium of PB but preferences of patients are poorly understood. OBJECTIVE: to study the patients' preferences and beliefs regarding PB and their influence on adherence and serum phosphate. METHODS: A cross-sectional cohort study was performed. A total of 121 hemodialysis patients answered a specific questionnaire in which they were questioned about adherence, the type of PB they preferred and the reasons for their choice. All patients questioned tasted two or three PB. The consequence of non-adherence to PB was estimated indirectly by determination of serum phosphorus. RESULTS: Specific noncompliance with PB medication was recognized by 21.4% of patients. Patients non-adherent specifically to PB were more likely to have P levels >5.5 mg/dl (χ(2): 4.7; 95% CI 1.07-6.5; p = 0.03). Paradoxically, patients non-adherent showed greater knowledge of the use (χ(2): 17.3; 95% CI -2.2-10.1; p <0.0001) and importance of the drug (χ(2): 10.4; 95% CI -1.5-6.6; p = 0.001). The percentage of patients prescribed binders they did not like was 54.5%. Patients who were taking PB they did not like had a greater risk of having P levels >5.5 mg/dl) (χ(2): 13.3; 95% CI -1.1-1.5; p = 0.0001). Calcium acetate was the preferred PB in 47.1% of patients, lanthanum carbonate in 40%, sevelamer in 20.6% and aluminum hydroxide in 19.4%. The reasons claimed by patients for their negative ratings of PB were the type of dosage form, the taste, the number of tablets and gastric intolerance. Gastric intolerance and bad taste were more frequent in aluminum hydroxide patients (19.4% and 22.2%, respectively). Sevelamer received complaints about its dosage form because the tablets were too large and a large number of tablets were required (27.2%). 17.7% of patient who were taking lanthanum carbonate did not like the chewable tablets. CONCLUSION: patients who were taking binders that they did not like had worse serum P levels and were prescribed higher doses of binders. Knowing patients' preferences about the drugs prescribed may be a key factor in achieving adequate adherence to treatment.

Management of anastrozole-induced bone loss in breast cancer patients with oral risedronate: results from the ARBI prospective clinical trial.

INTRODUCTION: The aim of this multicenter, phase III, prospective open label clinical trial was to investigate the effect of risedronate (R) on bone mineral density (BMD) in postmenopausal, early breast cancer (BC) patients scheduled to receive anastrozole (A). METHODS: Pre-treatment BMD of 213 patients with hormone receptor-positive BC was evaluated at lumbar spine (LS) and hip (HP). Patients were categorized according to their baseline BMD T-score as being at low, moderate and high risk of osteoporosis. Low risk patients received anastrozole only (A), moderate risk were randomized to anastrozole +/- risedronate (A+/-R) administration and high risk patients received anastrozole + risedronate (A+R). Anastrozole was given at a dosage of 1 mg/day while oral risedronate was given at 35 mg/week. BMD was then assessed at 12 and 24 months. All patients received daily supplements of calcium (1000 mg/day) and vitamin D (400 IU/day). RESULTS: At 24 months, in the moderate risk group, treatment with A+R resulted in a significant increase in BMD at LS and HP compared to treatment with A only (5.7% v -1.5%, Wilcoxon test P = 0.006, and 1.6% v -3.9% Wilcoxon test P = 0.037, respectively), while no significant difference was found at 12 months; 24.3% of the patients moved to normal BMD region. In the high risk group, a significant increase for LS was detected both at 12 and 24 months (6.3% and 6.6%, P < 0.001) but not for HP; BMD in 14% of patients improved to the osteopenic region. In the low risk group, a significant decrease of BMD was detected at 12 months for LS and HP (-5.3% P < 0.001 and -2.4% P < 0.001, respectively,); at 24 months, a significant decrease of BMD was detected only for LS (-2.5%, P < 0.001). However, 22% of patients became osteopenic and only 4% became osteoporotic. CONCLUSIONS: The addition of oral risedronate in post-menopausal breast cancer patients receiving anastrozole has a favorable effect on BMD. Patients with pre-treatment osteopenic to osteoporotic status should be treated with a combination of both therapies in order to avoid bone loss induced by aromatase inhibition. Patients with normal BMD before starting treatment with anastrozole have a very low risk to develop osteoporosis.

Central opioid peptide-containing neurons mediates therapeutic effect of short-pulse gastric electrical stimulation on dyspepsia-like symptoms in dogs.

This study investigated whether the curative effect of short-pulse gastric electrical stimulation (GES) on the vasopressin-induced dyspeptic symptoms was mediated by central opioid peptide-producing neurons. Five female beagle dogs implanted with 1 pair of electrodes in gastric serosa were used in a two-experiment study. In experiment one, the brain was scanned by positron emission tomography in 3 dogs with and without short-pulse GES, and the radioactivity in nuclei of solitary tract (NST) and hypothalamus was detected. Experiment two was composed of 4 sessions. In session one, the dogs were injected with vasopressin in the absence of short-pulse GES. With session two, the short-pulse GES was simultaneously given via the electrodes with the injection of vasopressin. In sessions three and four, naloxone and naloxone methiodide was administered respectively in the presence of short-pulse GES. Motion sickness-like symptoms were scored and compared among the different sessions. The results showed that the short-pulse GES significantly increased the radioactivity in NST and hypothalamic nuclei (P<0.05, vs control). The short-pulse GES could ameliorate the vasopressin-induced motion sickness-like symptoms in dogs. Naloxone, but not naloxone methiodide could attenuate the curative effects of short-pulse GES. It is concluded that NST and hypothalamic nuclei may participate in the mediation of the curative effects of short-pulse GES on dyspepsia-like symptoms. Central opioid peptide-containing neurons presumably mediate the therapeutic effect on dyspeptic symptoms of short-pulse GES.

Adaptive upregulation of gastric and hypothalamic ghrelin receptors and increased plasma ghrelin in a model of cancer chemotherapy-induced dyspepsia.

Chemotherapy treatment can lead to delayed gastric emptying, early satiety, anorexia, nausea and vomiting, described collectively as the cancer-associated dyspepsia syndrome (CADS). Administration of ghrelin (GHRL), an endogenous orexigenic peptide known to stimulate gastric motility, has been shown to reduce the symptoms of CADS induced in relevant animal models with the potent chemotherapeutic agent, cisplatin. We examined the effects in the rat of cisplatin (6 mg/kg i.p.) treatment on the expression of GHRL and ghrelin receptor (GHSR) mRNAs in the hypothalamus and the stomach at a time-point (2 days) when the effects of cisplatin are pronounced. In addition, plasma levels of GHRL (acylated and total including des-acyl GHRL) were measured and the effect on these levels of treatment with the synthetic glucocorticoid dexamethasone (2 mg/kg s.c. bd.) was investigated. Cisplatin increased GHSR mRNA expression in the stomach (67%) and hypothalamus (52%) but not GHRL mRNA expression and increased the percentage of acylated GHRL (7.03+/-1.35% vs. 11.38+/-2.40%) in the plasma. Dexamethasone reduced the plasma level of acylated GHRL and the percentage of acylated GHRL to values below those in animals treated with saline alone (7.03+/-1.35% vs. 2.60+/-0.49%). Our findings support the hypothesis that an adaptive upregulation of the ghrelin receptor may occur during cancer chemotherapy-associated dyspepsia. This may have a role in defensive responses to toxic challenges to the gut. In addition, our results provide preliminary evidence for glucocorticoid modulation of plasma ghrelin levels.