Tongbian formula alleviates slow transit constipation by increasing intestinal butyric acid to activate the 5-HT signaling.

Slow transit constipation (STC) is a long-lasting and prevalent intestinal condition, marked by hard, dry feces. The primary cause of STC may be attributed to an imbalance in the gut's microbial community and alterations in its metabolic byproducts. Tongbian formula (TB), a traditional Chinese medicinal formula, has been used to treat STC and shows a great effect on relieving constipation. The role of TB in regulating intestinal microbiota has not been fully elucidated. Herein, we investigated the potential effect of TB on gut microbiota and further explored the potential mechanism behind its effects. Our study demonstrated that TB significantly increased fecal water content and intestinal ink propulsion rate in loperamide (Lope)-induced STC rats. 5-HT signaling was suppressed in STC colon tissue, and the abundance of butyric acid (BA) in colonic contents was significantly down-regulated after Lope treatment. Notably, TB administration led to the restoration of microbial dysbiosis and the up-regulation of BA content, subsequently activating 5-HT signaling pathways. When BA was combined with a tryptophan hydroxylase-1 (TPH1) inhibitor, which is crucial for 5-HT synthesis, its therapeutic efficacy for treating STC was compromised. TB alleviates STC by reversing the intestinal microbiota imbalance and activating the 5-HT signaling in the colon through increasing BA levels. These findings suggest that TB is an ideal candidate for STC treatment.

Prunus persica (L.) Batsch blossom soluble dietary fiber synergia polyphenol improving loperamide-induced constipation in mice via regulating stem cell factor/C-kit, NF-κB signaling pathway and gut microbiota.

This study aimed to investigate the ameliorating effects of peach blossom soluble dietary fiber (PBSDF) and polyphenol (PBP) combinations on loperamide (Lop)-induced constipation in mice, together with the possible mechanism of action. The results demonstrated that the combined use of PBSDF and PBP could synergistically accelerate the gastrointestinal transit rate and gastric emptying rate, shorten first red fecal defecation time, accelerate the frequency of defecation, regulate the abnormal secretion of gastrointestinal neurotransmitters and pro-inflammatory cytokines, and down-regulate the expressions of AQP3 and AQP8. Western blotting and RT-qPCR analysis confirmed that PBSDF + PBP up-regulated the protein and mRNA expressions of SCF and C-kit in SCF/C-kit signaling pathway, and down-regulated pro-inflammatory mediator expressions in NF-κB signaling pathway. 16S rRNA sequencing showed that the diversity of gut microbiota and the relative abundance of specific strains, including Akkermansia, Bacteroides, Ruminococcus, Lachnospiraceae_NK4A136_group, and Turicibacter, rehabilitated after PBSDF + PBP intervention. These findings suggested that the combination of a certain dose of PBSDF and PBP had a synergistic effect on attenuating Lop-induced constipation, and the synergistic mechanism in improving constipation might associated with the regulating NF-κB and SCF/C-kit signaling pathway, and modulating the specific gut strains on constipation-related systemic types. The present study provided a novel strategy via dietary fiber and polyphenol interactions for the treatment of constipation.

Nandrolone decanoate impairs gastrointestinal motility and duodenal morphometry in moderately exercised rats.

The misuse of anabolic androgenic steroid associated or not with physical workouts disrupts gastrointestinal (GI) function homeostasis. Our goal was to investigate the effects of nandrolone decanoate (ND) and moderate swimming on the GI transit of solid meals, GI motor contractility, and intestinal histology in rats. Male Wistar rats were allocated to four groups that received intramuscular injections of ND (5.0 mg/kg) or vehicle (60.0 µL) and were submitted or not to swimming sessions (60 min, 5% body weight overload) for 4 weeks. Gastric emptying, intestinal transit, in vitro GI contractility, intestinal morphometry, and duodenal mucosal mast cells were evaluated in all experimental groups. ND treatment accelerated gastric emptying, slowed small intestine transit time, enhanced gastric carbachol-mediated reactivity, decreased crypt depth and villus height, reduced mucosal thickness, and increased the circular and longitudinal muscle layer thickness of the duodenum in sedentary rats. Moderate exercise accelerated intestinal transit time and reduced submucosa thickness. In vehicle-treated animals, a strong negative correlation was found between intestinal transit and mucosal mast cells, which was reversed by ND treatment. Combining ND treatment and swimming accelerated gastric emptying, increased duodenal cholinergic reactivity, inhibited the sodium nitroprusside relaxing response, increased the number of duodenal mast cells, decreased villus height, and increased the thickness of all muscle layers. ND changed the morphological and functional properties of the GI tract over time, with intense dysmotility, especially in sedentary animals, but moderate exercise seemed to have played a compensatory role in these harmful effects in the gut.

Phytochemical analysis and investigation of analgesic, anti-inflammatory, and antispasmodic activities of hydroethanolic extracts of Alternanthera dentata, Ocimum carnosum, and Plectranthus barbatus, three species with vernacular names derived from analgesic drugs.

ETHNOPHARMACOLOGICAL RELEVANCE: Plant vernacular names can provide clues about the popular use of a species in different regions and are valuable sources of information about the culture or vocabulary of a population. Several medicinal plants in Brazil have received names of medicines and brand-name products. AIM OF THE STUDY: The present work aimed to evaluate the chemical composition and pharmacological activity in the central nervous system of three species known popularly by brand names of analgesic, anti-inflammatory, antispasmodic, and digestive drugs. MATERIALS AND METHODS: Hydroethanolic extracts of Alternanthera dentata (AD), Ocimum carnosum (OC), and Plectranthus barbatus (PB) aerial parts were submitted to phytochemical analysis by HPLC-PAD-ESI-MS/MS and evaluated in animal models at doses of 500 and 1000 mg/kg. Mice were tested on hot plate, acetic acid-induced writing, formalin-induced licking, and intestinal transit tests. Aspirin and morphine were employed as standard drugs. RESULTS: The three extracts did not change the mice's response on the hot plate. Hydroethanolic extracts of AD and PB reduced the number of writhes and licking time, while OC was only effective on the licking test at dose of 1000 mg/kg. In addition, AD and OC reduced intestinal transit, while PB increased gut motility. CONCLUSIONS: Pharmacological tests supported some popular uses, suggesting peripheral antinociceptive and anti-inflammatory effects, while the phytochemical analysis showed the presence of several flavonoids in the three hydroethanolic extracts and steroids in PB, with some barbatusterol derivatives described for the first time in the species.

Combined antiallodynic effects of Neurotropin®-tramadol and Neurotropin®-mirogabalin in rats with L5-spinal nerve ligation.

We aimed to examine the efficacy of combination therapies of Neurotropin® with tramadol and Neurotropin with mirogabalin for neuropathic pain management. A neuropathic pain model (L5 spinal nerve ligation model: L5-SNL) using male Wistar rats was generated through tight ligation of the left fifth lumbar nerve using silk sutures. Mechanical allodynia was assessed using the 50% paw withdrawal threshold. The combined antiallodynic effects were evaluated using isobolographic analyses. Small intestinal transit was evaluated using the charcoal meal test, and motor coordination using the rota-rod test. Neurotropin (50-200 NU/kg, p.o.), tramadol (7.5-60 mg/kg, p.o.), and mirogabalin (3-30 mg/kg, p.o.) showed a dose-dependent antiallodynic effect in L5-SNL rats. The combined antiallodynic effects of Neurotropin and tramadol were additive or synergistic, whereas those of Neurotropin and mirogabalin were additive. Neurotropin (100-400 NU/kg, p.o.) did not affect the small intestinal transit, whereas tramadol (30-100 mg/kg, p.o.) significantly inhibited it. Neurotropin (100-400 NU/kg, p.o.) did not affect the walking time, whereas mirogabalin (10-100 mg/kg, p.o.) significantly decreased it. Neurotropin dose-dependently ameliorated mechanical allodynia in rats, and combination therapy with Neurotropin-tramadol or Neurotropin-mirogabalin may alleviate neuropathic pain without aggravating the adverse effects of tramadol and mirogabalin.

Modified Zhizhu Pill improves the loperamide-induced slow transit constipation via gut microbiota and neurotransmitters in microbiota-gut-brain axis.

BACKGROUND: Slow-transmission constipation is a type of intractable constipation with unknown etiology and unclear pathogenesis. OBJECTIVE: The intention of this study was to evaluate the therapeutic effect and possible mechanism of Modified Zhizhu Pills on loperamide-induced slow transit constipation. METHODS: The effects of the Modified Zhizhu Pill were evaluated in a rat model of constipation induced by subcutaneous administration of loperamide. Fecal parameters (fecal count, fecal water content, and fecal hardness) were measured in constipated rats. The substance, target, and pathway basis of the Modified Zhizhu Pill on constipation was investigated using network pharmacology. The microflora in rats was determined. Serum neurotransmitters (acetylcholine and 5-hydroxytryptamine) were measured in rats and their relationship with the gut microbiota was assessed. RESULTS: Modified Zhizhu Pill increased the number of bowel movements and fecal water content, and decreased fecal hardness and transit time. Network pharmacological analysis showed that Modified Zhizhu Pill can target multiple constipation-related targets and pathways through multiple potential active ingredients. Modified Zhizhu Pill alleviated loperamide-induced microbiota dysbiosis. Modified Zhizhu Pill increased serum 5-hydroxytryptamine and acetylcholine. The increase in serum 5-hydroxytryptamine and acetylcholine was associated with rat gut microbiota. CONCLUSION: These results suggest that Modified Zhizhu Pill may increase intestinal motility and ultimately relieve constipation by improving microecological dysbiosis and neurotransmission.

Opium tincture has anti-propulsive effects in patients with chronic diarrhea: a randomized, placebo-controlled, and cross-over trial.

OBJECTIVE: Chronic diarrhea affects approximately 5% of the population. Opioids inhibit gastrointestinal motility, and opium tincture has shown anti-propulsive effects in healthy, but no controlled studies of its clinical efficacy exist. We aimed to investigate the anti-propulsive and central nervous system (CNS) effects of opium tincture in patients with chronic diarrhea. MATERIALS AND METHODS: The study was a randomized, double-blinded, placebo-controlled, cross-over trial in subjects with chronic diarrhea refractory to standard treatment. Participants received opium tincture or placebo during two intervention periods, each lasting seven days. Bowel movements were recorded daily, and gastrointestinal transit time was investigated with the wireless motility capsule system. Gastrointestinal symptoms, health-related quality of life, and CNS effects (pupil size, reaction time, memory, and general cognition) were also investigated, along with signs of addiction. RESULTS: Eleven subjects (mean age: 45 ± 17 years, 46% males) with a median of 4.7 daily bowel movements were included. The number of daily bowel movements was reduced during opium tincture treatment to 2.3 (p = 0.045), but not placebo (3.0, p = 0.09). Opium tincture prolonged the colonic transit time compared to placebo (17 h vs. 12 h, p < 0.001). In both treatment arms, there were no changes in self-reported gastrointestinal symptoms, health-related quality of life, or CNS effects, and no indication of addiction was present. CONCLUSION: Opium tincture induced anti-propulsive effects in patients with chronic diarrhea refractory to standard treatment. This indicates that opium tincture is a relevant treatment strategy for selected patients with chronic diarrhea. Moreover, no evidence of opioid-induced sedation or addiction was found.Trial Registration Number: NCT05690321 (registered 2023-01-10).

MoPill a novel gastrointestinal positioning system (GPS): New technology to navigate the alimentary tract highway.

BACKGROUND: Evaluation of gut motility in clinical practice is currently limited. A novel medical system (MoPill™) consisting of a capsule that wirelessly transmits radiofrequency signals to assess motility via 3D location, was used to conduct this study. The objectives were to: (1) confirm the safety of the MoPill™ system; (2) compare the 3D location transmitted by the capsule to its location captured by abdominal x-rays; 3 determine gastric emptying (GE), whole gut transit time (WGTT) and segmental transit times. METHODS: The MoPill™ system consists of an electronic capsule (2 × 1.2 cm), eight color-coded adhesive sensors (6 × 5.5 cm), a recorder (15 × 11 × 2 cm), and software on a laptop. Four sensors were applied to the abdomen and four to the back. Healthy subjects who had fasted overnight ingested a 250-calorie protein bar, 17 oz. of water, followed by an activated capsule. No further caloric contents were permitted for the next 5 h. At 1, 5, and 24 h (if the capsule had not been expelled), upright abdominal X-rays (AP and lateral) were obtained to assess the location of the capsule, which was compared to the gastrointestinal positioning system (GPS) location determined by the MoPill™ system. Identification of the capsule's anatomical location by the MoPill™ system was based on (1) the 3D (x, y, z) location; (2) time; (3) trajectory (e.g., going up the right side of the body signified ascending colon); (4) frequency of contractions (e.g., 3 cycles/min for the stomach); and (5) milestone relationship (e.g., pyloric passage must follow the end of gastric contractions). GE was determined first by the end of the 3 cycles/min rhythmic movement of the stomach and then again by pyloric expulsion on 3D location. Small intestine transit was taken as the duration from pyloric expulsion to arrival in the cecum. Colon transit time was determined by calculating the duration from 3D arrival in the cecum to passage of the capsule out of the body (i.e., loss of signal accompanying a bowel movement). KEY RESULTS: Ten healthy subjects (five women; mean age 34; mean BMI 24) were enrolled, and nine provided reliable data. The variation between the x-ray and the estimated (i.e., identified by the MoPill™ system) location of the capsule was within an average of 3.5 cm (range 0.9-9.4 cm). The mean GE was 3.1 h. The small intestine's mean transit time was 4.3 h. The mean colonic transit time was 17.6 h. There were no adverse events recorded during the study. CONCLUSIONS & INFERENCES: MoPill™ is a novel gastrointestinal positional system that accurately identifies the location of a capsule compared to an X-ray. MoPill™ system also recognizes GE, small bowel, colonic, and WGTT as well as segmental gut location and movement characteristics. MoPill™ offers the potential for new insights into GI motility disorders not attainable by current modalities.

Testing in functional constipation-What's new and what works.

BACKGROUND: Constipation is among the most common symptoms prompting a consultation with a paediatric gastroenterologist. While most patients will respond to lifestyle and dietary changes and conventional therapy, some may require diagnostic studies. AIM: To review the diagnostics studies used to evaluate children with functional constipation. MATERIALS AND METHODS: There is no evidence to support the routine use of abdominal X-rays in the evaluation of paediatric constipation. Colon transit by radiopaque markers (ROM) should be indicated when medical history does not match clinical findings, to guide colon manometry (CM) performance and to discriminate between faecal incontinence from functional constipation and non-retentive faecal incontinence. Colon scintigraphy may be useful as an alternative to ROM. Lumbar spine MRI may be indicated to evaluate for spinal abnormalities. The role of defecography has not been properly evaluated in children. Anorectal manometry in children is indicated primarily to evaluate anal resting pressure, presence and quality of the recto-anal inhibitory reflex and simulated defecation manoeuvres. The CM is indicated to guide surgical interventions after failing medical therapy. CONCLUSIONS: The goal of these studies is to identify treatable causes of constipation. Most of these studies are designed to evaluate anatomy, transit and/or colon/rectum motility function and are primarily indicated in those who fail to respond to conventional therapy.

Honey Added to Yogurt with Bifidobacterium animalis subsp. lactis DN-173 010/CNCM I-2494 Supports Probiotic Enrichment but Does Not Reduce Intestinal Transit Time in Healthy Adults: A Randomized, Controlled, Crossover Trial.

BACKGROUND: Honey improves probiotic survival in vitro. However, if this effect translates to humans has not been investigated. OBJECTIVES: We aimed to determine effects of honey plus yogurt containing the probiotic Bifidobacterium animalis subsp. lactis DN-173 010/CNCM I-2494 (B. animalis) on intestinal transit time, probiotic enrichment, digestive health, mood, and cognition in adults. METHODS: Sixty-six healthy adults (34 female; 33.6 ± 9.8 y; 24.6 ± 3.0 kg/m2) in a crossover trial were randomly assigned to 2-wk yogurt conditions in a counterbalanced order with ≥4-wk washout: 1) Honey (HON): yogurt plus honey and 2) Negative Control (NC): heat-treated yogurt plus sugar. Of the participants, n = 62 completed the trial, and n = 37 (17 female; 32.0 ± 8.3 y; 25.0 ± 2.9 kg/m2) elected to enroll in a third condition (a nonrandomized study extension) after ≥4-wk washout with a reference Positive Control (PC): yogurt plus sugar. At baseline and end of each of the 3 conditions, intestinal transit time was measured with dye capsules; probiotic abundance with fecal DNA 16S sequencing; digestive health with symptom/function records, Bristol stool consistency, Gastrointestinal Tolerability, and Gastrointestinal Quality of Life Index; mood with Positive and Negative Affect Schedule-Short Form, Depression Anxiety Stress Scales-42, Patient-Reported Outcomes Measurement Information System questionnaires, and an emotional image task; and cognition with a spatial reconstruction task. Data were analyzed using linear mixed-effects models (LMMs) with significance at P ≤ 0.05. Baseline and end data were included in the LMM, with fixed effects being treatment, time, treatment by time interaction, and baseline covariate, and the random effect being the participant. RESULTS: B. animalis was enriched in HON (d = 3.54; P = 0.0002) compared to controls with linear discriminant analysis effect size. Intestinal transit time, gastrointestinal health, mood, and cognition did not differ between conditions (LMM: Ps > 0.05). CONCLUSIONS: Yogurt + honey enriched B. animalis but did not reduce intestinal transit time or have other functional gastrointestinal, mood, or cognitive effects in adults. This trial was registered at www. CLINICALTRIALS: gov as NCT04187950 and NCT04901390.

Effects and mechanisms of sciadonic acid on colonic transit function through regulating 5-HT4/cAMP/PKA/AQP4 signaling pathway in STC model mice.

Torreya grandis (T. grandis) oil has been reported to alleviate symptoms of slow transit constipation (STC). However, the impact of sciadonic acid (SA), a distinctive fatty acid found in T. grandis oil, on the pathological progression of STC remains unclear. This study aimed to evaluate the effect of SA on STC and uncover the underlying mechanisms. The STC model was established by feeding Balb/c mice with loperamide. After 2 weeks of intervention, SA significantly improved weight loss and intestinal motility decline induced by STC, along with enhancing plasma indices and reducing colon pathological damage. SA effectively reversed the STC-induced decrease in the 5-HT4/cAMP/PKA/AQP4 signaling pathway genes and expression. Furthermore, 16S rRNA analysis demonstrated that SA mitigated the imbalance of the intestinal microbiota induced by STC, by reducing the ratio of Firmicutes to Bacteroidetes (F/B) and increasing the abundance of beneficial bacteria such as Akkermansia. In conclusion, SA intervention alleviated colonic dysfunction in STC mice. The activation of the SA-mediated 5-HT4/cAMP/PKA/AQP4 signaling pathway may serve as a potential target for STC treatment. These findings suggest that SA holds promise as a treatment option for STC and could potentially be extended to other related gut diseases for further investigation.

A Novel Herbal Composition Alleviates Functional Constipation, Reduces Gastrointestinal Transit Time, and Improves Bowel Function in Adults: A Double-Blind, Randomized Clinical Study.

BACKGROUND AND OBJECTIVE: A recent proof-of-concept pilot clinical study has demonstrated that consumption of CL18100F4, a proprietary herbal blend of Withania somnifera root and Abelmoschus esculentus fruit extracts, significantly relieved the participants from functional constipation and improved their quality of life. The objective of the present randomized, double-blind, placebo-controlled study was to reevaluate the efficacy and tolerability of CL18100F4 in a larger number of subjects. METHODS: Male and female subjects (n = 135; age: 25-60 years), selected through Rome-IV criteria for functional constipation, were randomized into placebo and 300 or 500 mg of CL18100F4 groups and supplemented daily over 60 consecutive days. The primary efficacy outcome measure was Patient Assessment of Constipation-Symptoms (PAC-SYM), evaluated at baseline and on days 7, 30, and 60 of supplementation. The secondary efficacy parameters included Patient Assessment of Constipation-Quality of Life (PAC-QOL), Gastrointestinal Symptom Rating Scale (GSRS) scores, Gastrointestinal Transit Time (GIT), and Complete Spontaneous Bowel Movement (CSBM). Serum levels of Interleukin (IL)-6, IL-10, cortisol, gastrin, serotonin, Diamine oxidase (DAO), and Zonulin were measured. RESULTS: CL18100F4 supplementation significantly (p < 0.001) reduced the PAC-SYM, PAC-QOL, GSRS scores, and GIT and improved CSBM scores. CL18100F4 significantly improved (p < 0.001) sleep quality and decreased depression and anxiety symptoms in the participants. Notably, relief in constipation symptoms and improved gastrointestinal (GI) function were reported starting from day 7. Furthermore, CL18100F4 supplementation significantly (p < 0.001) increased the serum levels of IL-10, DAO, serotonin, gastrin, reduced IL-6, cortisol, and Zonulin. No major adverse events were observed. Participants' vital signs, hematology, clinical biochemistry, and urinalysis parameters were within the normal ranges. CONCLUSION: The present investigation demonstrates that CL18100F4 is tolerable and efficacious in relieving functional constipation, alleviating GI dysfunction, and improving associated non-GI factors in male and female adults.

Drug dissolution and transit in a heterogenous gastric chyme after fed administration: Semi-mechanistic modeling and simulations for an immediate-release and orodispersible tablets containing a poorly soluble drug.

Mathematical models that treat the fed stomach content as a uniform entity emptied with a constant rate may not suffice to explain pharmacokinetic profiles recorded in clinical trials. In reality, phenomena such as the Magenstrasse or chyme areas of different pH and viscosity, play an important role in the intragastric drug dissolution and its transfer to the intestine. In this study, we investigated the data gathered in the bioequivalence trial between an immediate-release tablet (Reference) and an orally dispersible tablet (Test) with a poorly soluble weak base drug administered with or without water after a high-fat high-calorie breakfast. Maximum concentrations (Cmax) were significantly greater after administering the Reference product than the Test tablets, despite similar in vitro dissolution profiles. To explain this difference, we constructed a novel semi-mechanistic IVIVP model including a heterogeneous gastric chyme. The drug dissolution in vivo was modeled from the in vitro experiments in biorelevant media simulating gastric and intestinal fluids in the fed state (FEDGAS and FeSSIF). The key novelty of the model was separating the stomach contents into two compartments: isolated chyme (the viscous food content) that carries the drug slowly, and aq_chyme open for rapid Magenstrasse-like routes of drug transit. Drug distribution between these two compartments was both formulation- and administration-dependent, and recognized the respective drug fractions from the clinical pharmacokinetic data. The model's assumption about the nonuniform mixing of the API with the chyme, influencing differential drug dissolution and transit kinetics, led to simulating plasma concentration profiles that reflected well the variability observed in the clinical trial. The model indicated that, after administration, the Reference product mixes to a greater extent with aq_chyme, where the released drug dissolves better and transfers faster to the intestine. In conclusion, this novel approach underlines that diverse gastric emptying of different oral dosage forms may significantly impact pharmacokinetics and affect the outcomes of bioequivalence trials.

Antispasmodic and antidiarrheal effects of Juniperus oxycedrus L. on the jejunum in rodents.

Functional bowel disorders (FBD) have a major potential to degrade the standards of public life. Juniperus oxycedrus L. (J. oxycedrus) (Cupressaceae) has been described as a plant used in traditional medicine as an antidiarrheal medication. The present study is the first to obtain information on the antispasmodic and antidiarrheic effects of J. oxycedrus aqueous extract through in vitro and in vivo studies. An aqueous extract of J. oxycedrus (AEJO) was extracted by decoctioning air-dried aerial sections of the plant. Antispasmodic activity was tested in an isolated jejunum segment of rats exposed to cumulative doses of drogue extract. The antidiarrheic activity was tested using diarrhea caused by castor oil, a transit study of the small intestine, and castor oil-induced enteropooling assays in mice. In the jejunum of rats, the AEJO (0.1, 0.3 and 1 mg/ml) diminished the maximum tone induced by low K+ (25 mM), while it exhibited a weak inhibitory effect on high K+ (75 mM) with an IC50=0.49 ± 0.01 mg/ml and IC50=2.65 ± 0.16 mg/ml, respectively. In the contractions induced by CCh (10-6 M), AEJO diminished the maximum tone, similar to that induced by low K+ (25 mM). with an IC50=0.45 ± 0.02 mg/ml. The inhibitory effect of AEJO on low K+ induced contractions was significantly diminished in the presence of glibenclamide (GB) (0.3 µM) and 4-aminopyrimidine (4-AP) (100 µM), with IC50 values of 1.84 ± 0.09 mg/ml. and 1.63 ± 0.16 mg/ml, respectively). The demonstrated inhibitory effect was similar to that produced by a non-competitive antagonist acting on cholinergic receptors and calcium channels. In castor oil-induced diarrhea in mice, AEJO (100, 200, and 400 mg/kg) caused an extension of the latency time, a reduced defecation frequency, and a decrease in the amount of wet feces compared to the untreated group (distilled water). Moreover, it showed a significant anti-motility effect and reduced the amount of fluid accumulated in the intestinal lumen at all tested doses. These findings support the conventional use of Juniperus oxycedrus L. as a remedy for gastrointestinal diseases.

Diagnosis of Chronic Constipation.

Patients with chronic constipation (CC) usually complain of mild to severe symptoms, including hard or lumpy stools, straining, a sense of incomplete evacuation after a bowel movement, a feeling of anorectal blockage, the need for digital maneuver to assist defecation, or reduced stool frequency. In clinical practice, healthcare providers need to check for 'alarm features' indicative of a colonic malignancy, such as bloody stools, anemia, unexplained weight loss, or new-onset symptoms after 50 years of age. In the Seoul Consensus on the diagnosis and treatment of chronic constipation, the Bristol stool form scale, colonoscopy, and digital rectal examination are useful for objectively evaluating the symptoms and making a differential diagnosis of the secondary cause of constipation. If patients with CC improve to lifestyle modification or first-line therapies, the effort to determine the subtypes of CC is usually not considered. On the other hand, if conventional therapeutic strategies fail, diagnostic testing needs to be considered to distinguish between the different subtypes of functional constipation (normal-transit constipation, slow transit constipation, or defecatory disorder) because these subtypes of constipation have different therapeutic implications and a correct diagnosis is critical. In the Seoul consensus, physiological testing is recommended for patients with functional constipation who have failed to respond to treatment with available laxatives (for a minimum of 12 weeks and recommended a therapeutic regimen) or who are strongly suspected of having a defecatory disorder. The Seoul consensus contains statements of physiological testing, including balloon expulsion test, anorectal manometry, defecography, and colon transit time.

Scintigraphy of Gastrointestinal Motility: Best Practices in Assessment of Gastric and Bowel Transit in Adults.

Various radiologic examinations and other diagnostic tools exist for evaluating gastrointestinal diseases. When symptoms of gastrointestinal disease persist and no underlying anatomic or structural abnormality is identified, the diagnosis of functional gastrointestinal disorder is frequently applied. Given its physiologic and quantitative nature, scintigraphy often plays a central role in the diagnosis and treatment of patients with suspected functional gastrointestinal disorder. Most frequently, after functional gallbladder disease is excluded, gastric emptying scintigraphy (GES) is considered the next step in evaluating patients with suspected gastric motility disorder who present with upper gastrointestinal symptoms such as dyspepsia or bloating. GES is the standard modality for detecting delayed gastric emptying (gastroparesis) and the less commonly encountered clinical entity, gastric dumping syndrome. Additionally, GES can be used to assess abnormalities of intragastric distribution, suggesting specific disorders such as impaired fundal accommodation or antral dysfunction, as well as to evaluate gastric emptying of liquid. More recently, scintigraphic examinations for evaluating small bowel and large bowel transit have been developed and validated for routine diagnostic use. These can be performed individually or as part of a comprehensive whole-gut transit evaluation. Such scintigraphic examinations are of particular importance because clinical assessment of suspected functional gastrointestinal disorder frequently fails to accurately localize the site of disease, and those patients may have motility disorders involving multiple portions of the gastrointestinal tract. The authors comprehensively review the current practice of gastrointestinal transit scintigraphy, with diseases and best imaging practices illustrated by means of case review. ©RSNA, 2024 See the invited commentary by Maurer and Parkman in this issue.

ARE THERE ADVANTAGES IN DOUBLE TRANSIT RECONSTRUCTION AFTER TOTAL GASTRECTOMY IN PATIENTS WITH GASTRIC CANCER? A SYSTEMATIC REVIEW.

BACKGROUND: Curative treatment for gastric cancer involves tumor resection, followed by transit reconstruction, with Roux-en-Y being the main technique employed. To permit food transit to the duodenum, which is absent in Roux-en-Y, double transit reconstruction has been used, whose theoretical advantages seem to surpass the previous technique. AIMS: To compare the clinical evolution of gastric cancer patients who underwent total gastrectomy with Roux-en-Y and double tract reconstruction. METHODS: A systematic review was carried out on Web of Science, Scopus, EmbasE, SciELO, Virtual Health Library, PubMed, Cochrane, and Google Scholar databases. Data were collected until June 11, 2022. Observational studies or clinical trials evaluating patients submitted to double tract (DT) and Roux-en-Y (RY) reconstructions were included. There was no temporal or language restriction. Review articles, case reports, case series, and incomplete texts were excluded. The risk of bias was calculated using the Cochrane tool designed for randomized clinical trials. RESULTS: Four studies of good methodological quality were included, encompassing 209 participants. In the RY group, there was a greater reduction in food intake. In the DT group, the decrease in body mass index was less pronounced compared to preoperative values. CONCLUSIONS: The double tract reconstruction had better outcomes concerning body mass index and the time until starting a light diet; however, it did not present any advantages in relation to nutritional deficits, quality of life, and post-surgical complications.

Sleeve gastrectomy with duodenoileal bipartition using linear magnets: feasibility and safety at 1-year follow-up.

BACKGROUND: Single-anastomosis metabolic/bariatric surgery procedures may lessen the incidence of anastomotic complications. This study aimed to evaluate the feasibility and safety of performing side-to-side duodenoileal (DI) bipartition using magnetic compression anastomosis (MCA). In addition, preliminary efficacy, quality of life (QoL), and distribution of food through the DI bipartition were evaluated. METHODS: Patients with a body mass index (BMI) of ≥35.0 to 50.0 kg/m2 underwent side-to-side DI bipartition with the magnet anastomosis system (MS) with sleeve gastrectomy (SG). By endoscopic positioning, a distal magnet (250 cm proximal to the ileocecal valve) and a proximal magnet (first part of the duodenum) were aligned with laparoscopic assistance to inaugurate MCA. An isotopic study assessed transit through the bipartition. RESULTS: Between March 14, 2022 to June 1, 2022, 10 patients (BMI of 44.2 ± 1.3 kg/m2) underwent side-to-side MS DI. In 9 of 10 patients, an SG was performed concurrently. The median operative time was 161.0 minutes (IQR, 108.0-236.0), and the median hospital stay was 3 days (IQR, 2-40). Paired magnets were expelled at a median of 43 days (IQR, 21-87). There was no device-related serious advanced event within 1 year. All anastomoses were patent with satisfactory diameters after magnet expulsion and at 1 year. Respective BMI, BMI reduction, and total weight loss were 28.9 ± 1.8 kg/m2, 15.2 ± 1.8 kg/m2, and 34.2% ± 4.1%, respectively. Of note, 70.0% of patients reported that they were very satisfied. The isotopic study found a median of 19.0% of the meal transited through the ileal loop. CONCLUSION: Side-to-side MCA DI bipartition with SG in adults with class II to III obesity was feasible, safe, and efficient with good QoL at 1-year follow-up. Moreover, 19% of ingested food passed directly into the ileum.

Mechanism of Mulberry Leaves and Black Sesame in Alleviating Slow Transit Constipation Revealed by Multi-Omics Analysis.

Traditional Chinese medicine (TCM) possesses the potential of providing good curative effects with no side effects for the effective management of slow transit constipation (STC), an intestinal disease characterized by colonic dyskinesia. Mulberry leaves (Morus alba L.) and black sesame (Sesamum indicum L.), referred to as SH, are processed and conditioned as per standardized protocols. SH has applications as food and medicine. Accordingly, we investigated the therapeutic potential of SH in alleviating STC. The analysis of SH composition identified a total of 504 compounds. The intervention with SH significantly improved intestinal motility, reduced the time for the first black stool, increased antioxidant activity, and enhanced water content, thereby effectively alleviating colon damage caused by STC. Transcriptome analysis revealed the SH in the treatment of STC related to SOD1, MUC2, and AQP1. The analysis of 16S rRNA gene sequences indicated notable differences in the abundance of 10 bacteria between the SH and model. Metabolomic analysis further revealed that SH supplementation increased the levels of nine metabolites associated with STC. Integrative analysis revealed that SH modulated amino acid metabolism, balanced intestinal flora, and targeted key genes (i.e., SOD1, MUC2, AQP1) to exert its effects. SH also inhibited the AQP1 expression and promoted SOD1 and MUC2 expression.