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Introduction: Gastrointestinal neuropathies are frequently found in diabetic patients. The pathogenesis of diabetic gastroparesis (DG) is multifactorial. The usual treatment for DG includes dietary modifications, prokinetic and antiemetic agents. There is increasing demand for more effective medicines to treat DG. The current study was conducted on the Pistacia lentiscus stem extract to add to the armamentarium of DG treatment and to find the efficacy of P. lentiscus plant extract (mastic gum) in comparison to levosulpiride in DG for improvement in gastroparesis symptoms and gastric emptying scintigraphy (GES) in a single centric double-blind non-inferiority randomised control trial. Methods: Thirty-eight individuals were recruited and equally randomised into two study groups based on Gastroparesis Cardinal Symptom Index (GCSI) score and TC99 Radionuclide GES, mastic gum group and levosulpiride group. Both pre and post-intervention (8 weeks) GCSI scores were calculated, GES was performed to quantify the improvement in gastric emptying. Power analysis was performed using G*POWER software version 3.1.9.7 and data analysis using SPSS 23.0, variables measured in mean ± standard deviation (SD). Various statistical tests were used such as independent t-test, Chi-square test or Fisher's exact test, Wilcox Mann–Whitney test, analysis of variance (ANOVA) test, and posthoc pairwise tests. Results: The mastic gum is found effective in the improvement of 4 h gastric emptying percentage from the mean (SD) 76.60 (± 9.96) to mean (SD) 97.20 (2.17)% (P < 0.001). Mastic gum has the property of HbA1c reduction, which is more significant than that of levosulpiride (P = 0.044). Mastic gum also had significant Low density lipoprotein (LDL) (mg/dL) levels reduction, (P < 0.001), compared to levosupiride. An absolute increase was observed in haemoglobin (HB) level in mastic gum at a 2-month mean (SD) of 1.03 (0.77) (g/dL) (P-value

Introduction: Gastrointestinal neuropathies are frequently found in diabetic patients. The pathogenesis of diabetic gastroparesis (DG) is multifactorial. The usual treatment for DG includes dietary modifications, prokinetic and antiemetic agents. There is increasing demand for more effective medicines to treat DG. The current study was conducted on the Pistacia lentiscus stem extract to add to the armamentarium of DG treatment and to find the efficacy of P. lentiscus plant extract (mastic gum) in comparison to levosulpiride in DG for improvement in gastroparesis symptoms and gastric emptying scintigraphy (GES) in a single centric double-blind non-inferiority randomised control trial. Methods: Thirty-eight individuals were recruited and equally randomised into two study groups based on Gastroparesis Cardinal Symptom Index (GCSI) score and TC99 Radionuclide GES, mastic gum group and levosulpiride group. Both pre and post-intervention (8 weeks) GCSI scores were calculated, GES was performed to quantify the improvement in gastric emptying. Power analysis was performed using G*POWER software version 3.1.9.7 and data analysis using SPSS 23.0, variables measured in mean ± standard deviation (SD). Various statistical tests were used such as independent t-test, Chi-square test or Fisher's exact test, Wilcox Mann–Whitney test, analysis of variance (ANOVA) test, and posthoc pairwise tests. Results: The mastic gum is found effective in the improvement of 4 h gastric emptying percentage from the mean (SD) 76.60 (± 9.96) to mean (SD) 97.20 (2.17)% (P < 0.001). Mastic gum has the property of HbA1c reduction, which is more significant than that of levosulpiride (P = 0.044). Mastic gum also had significant Low density lipoprotein (LDL) (mg/dL) levels reduction, (P < 0.001), compared to levosupiride. An absolute increase was observed in haemoglobin (HB) level in mastic gum at a 2-month mean (SD) of 1.03 (0.77) (g/dL) (P-value <0.001). Conclusions: To our knowledge, this is the first study to compare the effect of levosulpiride with mastic gum concerning improvement in diabetic gastroparesis (DG) using GES. In the study, mastic gum was found to have great properties to improve DG with many important pleiotropic effects. [ABSTRACT FROM AUTHOR]

Summary: Background & aim: To understand whether any change in gastric emptying (GE) is physiologically relevant, it is important to identify its variability. Information regarding the variability of GE in overweight and obese individuals is lacking. The aim of this study was to determine the reproducibility of GE in overweight and obese males. Methods: Fifteen overweight and obese males [body mass index 30.3 (4.9) kg/m2] completed two identical GE tests 7 days apart. GE of a standard pancake breakfast was assessed by 13C-octanoic acid breath test. Data are presented as mean (±SD). Results: There were no significant differences in GE between test days (half time (t 1/2): 179 (15) and 176 (19 min), p = 0.56; lag time (t lag): 108 (14) and 104 (8) min, p = 0.26). Mean intra-individual coefficient of variation for t 1/2 was 7.9% and t lag 7.5%. Based on these findings, to detect a treatment effect in a paired design with a power of 80% and α = 0.05, minimum mean effect sizes for t 1/2 would need to be ≥14.4 min and t lag ≥ 8.1 min. Conclusions: These data show that GE is reproducible in overweight and obese males and provide minimum mean effect sizes required to detect a hypothetical treatment effect in this population. [Copyright &y& Elsevier]

Gastrointestinal dysmotility is one of the nonmotor symptoms of Parkinson's disease (PD). Gastroparesis and upregulated β-adrenoceptors (β-ARs) have been reported in rats with bilateral microinjection of 6-hydroxydopamine (6-OHDA) in the substantia nigra, but the underlying mechanism is unclear. The aim of the current study is to investigate the role of β-ARs in gastroparesis in 6-OHDA rats. Gastric motility was studied through strain gauge measurement. Immunofluorescence, real-time reverse transcription-polymerase chain reaction and Western blotting were performed to examine the expression of β-ARs. Norepinephrine (NE) inhibited gastric motility in a dose-dependent fashion in both control and 6-OHDA rats, but much stronger adrenergic reactivity was observed in the 6-OHDA rats. The inhibition of gastric motility by NE in both control and 6-OHDA rats was not affected by tetrodotoxin, a neural sodium channel blocker. Blocking β1-AR or β2-AR did not affect the inhibition of strip contraction by NE in control rats, but β1-AR blockage obviously enhanced the half maximal inhibitory concentration value of NE in 6-OHDA rats. Selective inhibition of β3-AR blocked the effect of NE significantly in both control and 6-OHDA rats. The protein expression of β1-AR, but not β2-AR and β3-AR in gastric muscularis externa was increased significantly in 6-OHDA rats. In conclusion, β3-AR involves the regulation of gastric motility in control rats, whereas the upregulation of β1-AR is responsible for enhanced NE reactivity in 6-OHDA rats and therefore is involved in the formation of gastroparesis. The effect of both β1-AR and β3-AR on gastric motility is independent of the enteric nervous system. [ABSTRACT FROM AUTHOR]

Abstract: Lipopolysaccharide (LPS) inhibits gastric antral contractions in conscious rats. Since LPS regulates corticotropin-releasing factor type 2 receptor (CRF2) expression in the rat stomach, and activation of peripheral CRF2 alters gastric motility, we tried to determine the role of peripheral CRF2 in the LPS-induced suppression of gastric antral contractions. Intraluminal gastric pressure waves were measured in freely moving conscious non-fasted rats using the perfused manometric method. We assessed the area under the manometric trace as the motor index (MI), and compared this result with those obtained 1h before and after intraperitoneal injection of drugs. LPS (0.2mg/kg) significantly decreased MI. Indomethacin (10mg/kg) itself did not alter MI but blocked this inhibitory action by LPS. Astressin 2-B (200μg/kg), a selective CRF2 antagonist, modified neither the basal MI nor the action by LPS. Meanwhile, urocortin 2 (30μg/kg), a selective CRF2 agonist, reversed the suppression by LPS without affecting the basal MI. This action by urocortin 2 was blocked by pretreatment with astressin 2-B. In conclusion, LPS inhibited gastric antral contractions possibly through a prostaglandin-dependent pathway. Peripheral CRF2 stimulation reversed this response by LPS. [Copyright &y& Elsevier]

Highlights: [•] l-Dopa/carbidopa, a medication for Parkinson's disease delays gastric emptying in fasted rats. [•] l-Dopa/carbidopa also reduces the postprandial antral and duodenal motility in food-restricted rats. [•] Rikkunshito, a kampo medicine prevents l-dopa/carbidopa-inhibited gastric emptying and motility. [•] Ghrelin antagonist partially reverses the rikkunshito preventive effect. [•] Rikkunshito prevents l-dopa/carbidopa-inhibited gastric emptying in a Parkinson's rat model. [Copyright &y& Elsevier]

Abstract: Objective: The G protein-coupled receptor 55 (GPR55) is a novel cannabinoid (CB) receptor, whose role in the gastrointestinal (GI) tract remains unknown. Here we studied the significance of GPR55 in the regulation of GI motility. Design: GPR55 mRNA and protein expression were measured by RT-PCR and immunohistochemistry. The effects of the GPR55 agonist O-1602 and a selective antagonist cannabidiol (CBD) were studied in vitro and in vivo and compared to a non-selective cannabinoid receptor agonist WIN55,212-2. CB1/2 −/− and GPR55−/− mice were employed to identify the receptors involved. Results: GPR55 was localized on myenteric neurons in mouse and human colon. O-1602 concentration-dependently reduced evoked contractions in muscle strips from the colon (∼60%) and weakly (∼25%) from the ileum. These effects were reversed by CBD, but not by CB1 or CB2 receptor antagonists. I.p. and i.c.v. injections of O-1602 slowed whole gut transit and colonic bead expulsion; these effects were absent in GPR55−/− mice. WIN55,212-2 slowed whole gut transit effects, which were counteracted in the presence of a CB1 antagonist AM251. WIN55,212-2, but not O-1602 delayed gastric emptying and small intestinal transit. Locomotion, as a marker for central sedation, was reduced following WIN55,212-2, but not O-1602 treatment. Conclusion: GPR55 is strongly expressed on myenteric neurons of the colon and it is selectively involved in the regulation of colonic motility. Since activation of GPR55 receptors is not associated with central sedation, the GPR55 receptor may serve as a future target for the treatment of colonic motility disorders. [Copyright &y& Elsevier]

Background & Aims: RM-131, a synthetic ghrelin agonist, greatly accelerates gastric emptying of solids in patients with type 2 diabetes and delayed gastric emptying (DGE). We investigated the safety and effects of a single dose of RM-131 on gastric emptying and upper gastrointestinal (GI) symptoms in patients with type 1 diabetes and previously documented DGE. Methods: In a double-blind cross-over study, 10 patients with type 1 diabetes (age, 45.7 ± 4.4 y; body mass index, 24.1 ± 1.1 kg/m2) and previously documented DGE were assigned in random order to receive a single dose of RM-131 (100 μg, subcutaneously) or placebo. Thirty minutes later, they ate a radiolabeled solid–liquid meal containing EggBeaters (ConAgra Foods, Omaha, NE), and then underwent 4 hours of gastric emptying and 6 hours of colonic filling analyses by scintigraphy. Upper GI symptoms were assessed using a daily diary, gastroparesis cardinal symptom index (total GCSI-DD) and a combination of nausea, vomiting, fullness, and pain (NVFP) scores (each rated on a 0−5 scale). Results: At screening, participants' mean level of hemoglobin A1c was 9.1% ± 0.5%; their total GCSI-DD score was 1.66 ± 0.38 (median, 1.71), and their total NVFP score was 1.73 ± 0.39 (median, 1.9). The t1/2 of solid gastric emptying was 84.9 ± 31.6 minutes when subjects were given RM-131 and 118.7 ± 26.7 when they were given a placebo. The median difference (Δ)was 33.9 minutes (interquartile range [IQR] -12, –49), or -54.7% (IQR, -21%,-110%). RM-131 decreased gastric retention of solids at 1 hour (P = .005) and 2 hours (P = .019). Numeric differences in t1/2 for gastric emptying of liquids, solid gastric emptying lag time, and colonic filling at 6 hours were not significant. Total GCSI-DD scores were 0.79 on placebo (IQR, 0.75, 2.08) and 0.17 on RM-131 (IQR, 0.00, 0.67; P = .026); NVFP scores were lower on RM-131 (P = .041). There were no significant adverse effects. Conclusions: RM-131 significantly accelerates gastric emptying of solids and reduces upper GI symptoms in patients with type 1 diabetes and documented DGE. ClinicalTrials.gov: NCT01394055. [Copyright &y& Elsevier]