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Medical Science Monitor : International... Jul 2019BACKGROUND The aim of this study was to evaluate the effects of a new type of dietary fiber - high specific volume polysaccharide (HSVP) - on fecal properties, serum...
BACKGROUND The aim of this study was to evaluate the effects of a new type of dietary fiber - high specific volume polysaccharide (HSVP) - on fecal properties, serum vasoactive intestinal peptide (VIP) concentration, intestinal flora count, and expression of the VIP-cAMP-PKA-AQP3 signaling pathway. MATERIAL AND METHODS Compound diphenoxylate was used in 48 healthy Wistar rats to establish a constipation model. Rats were divided into a normal control group, a constipation model group, an HSVP low-dose group, an HSVP medium-dose group, an HSVP high-dose group, and a fructose control group. We used colony count method, ELISA, WB, and RT-PCR to determine fecal moisture content, fecal hardness, fecal passage time, serum VIP concentration, number of intestinal bacteria, and VIP-cAMP-PKA-AQP3 signal pathway protein expression. RESULTS The constipation model was established successfully. HSVP (the medium dose was 10% and the high dose was 15%) improved fecal moisture content, reduced hardness, shortened fecal emptying time, increased intestinal bacteria, reduced serum VIP concentration, downregulated cAMP and PKAm RNA transcription, reduced protein expression, and reduced intestinal AQP3 expression. CONCLUSIONS HSVP improved constipation, increased the number of intestinal bacteria, and elevated expression of the VIP-cAMP-PKA-AQP3 signaling pathway. The mechanism of HSVP in regulating intestinal water metabolism in constipated rats may occur through the VIP-cAMP-PKA-AQP3 signaling pathway, and be closely related to changes in intestinal bacteria. The important role of the brain-gut-microbiome axis in the pathogenesis of constipation has been confirmed in this study.
Topics: Animals; Aquaporin 3; Constipation; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Dietary Fiber; Feces; Gastrointestinal Microbiome; Gastrointestinal Transit; Hardness; Humidity; Intestines; Polysaccharides; RNA, Messenger; Rats, Wistar; Transcription, Genetic; Treatment Outcome; Vasoactive Intestinal Peptide; Water
PubMed: 31280283
DOI: 10.12659/MSM.916526 -
Bioscience Reports May 2019Slow transit constipation (STC) is a common disease characterized by markedly delayed colonic transit time as a result of colonic motility dysfunction. It is well...
Slow transit constipation (STC) is a common disease characterized by markedly delayed colonic transit time as a result of colonic motility dysfunction. It is well established that STC is mostly caused by disorders of relevant nerves, especially the enteric nervous system (ENS). Colonic electrical stimulation (CES) has been regarded as a valuable alternative for the treatment of STC. However, little report focuses on the underlying nervous mechanism to normalize the delayed colonic emptying and relieve symptoms. In the present study, the therapeutic effect and the influence on ENS triggered by CES were investigated in STC beagles. The STC beagle model was established by oral administration of diphenoxylate/atropine and alosetron. Histopathology, electron microscopy, immunohistochemistry, Western blot analysis and immunofluorescence were used to evaluate the influence of pulse train CES on myenteric plexus neurons. After 5 weeks of treatment, CES could enhance the colonic electromyogram (EMG) signal to promote colonic motility, thereby improving the colonic content emptying of STC beagles. HE staining and transmission electron microscopy confirmed that CES could regenerate ganglia and synaptic vesicles in the myenteric plexus. Immunohistochemical staining showed that synaptophysin (SYP), protein gene product 9.5 (PGP9.5), cathepsin D (CAD) and S-100B in the colonic intramuscular layer were up-regulated by CES. Western blot analysis and immunofluorescence further proved that CES induced the protein expression of SYP and PGP9.5. Taken together, pulse train CES could induce the regeneration of myenteric plexus neurons, thereby promoting the colonic motility in STC beagles.
Topics: Animals; Colon; Constipation; Dogs; Electric Stimulation; Female; Myenteric Plexus; Neurons; Regeneration; Synaptophysin
PubMed: 31064818
DOI: 10.1042/BSR20182405 -
International Journal of Biological... Jul 2019The aim of this study is to probe new functions of a polysaccharide from Spirulina platensis (PSP) on constipation and intestinal microbiota in mice....
The aim of this study is to probe new functions of a polysaccharide from Spirulina platensis (PSP) on constipation and intestinal microbiota in mice. Diphenoxylate-induced constipation in mice was treated with different doses of PSP, followed by examining the defecation patterns, levels of acetyl cholinesterase (AchE), nitric oxide (NO), and tissue section histopathology. The composition of intestinal microbiota was determined by genome sequencing analysis of the 16S rDNA. This study found that the average molecular weight of PSP was 29, 600 Da, and mainly monosaccharides of PSP were rhamnose (24.7%), glucose (16.15%) and galactose (13.32%). The beneficial effects of PSP treatment include defecation improvement, increase of AchE activity, reduction of NO concentration, renovation of the damaged intestinal villus and affection on the expression of some related genes in the constipated mice. In addition, PSP had significant effects on the gut microbiota, showing the enhancement in abundance of beneficial bacteria including Akkermansia, Lactobacillus, Butyricimonas, Candidatus Arthromitus and Prevotella, and the reduction in abundance of harmful bacteria such as Clostridium and Dorea. The present s uncovered a new function of PSP, indicating that PSP could be used in constipation therapies.
Topics: Animals; Chorionic Villi; Constipation; Defecation; Diphenoxylate; Gene Expression Regulation; Intestines; Male; Mice; Mice, Inbred ICR; Neurotransmitter Agents; Polysaccharides, Bacterial; Spirulina; Water
PubMed: 31054300
DOI: 10.1016/j.ijbiomac.2019.04.209 -
Foods (Basel, Switzerland) Mar 2019This study compares the prevention effects of Shuidouchi with different fermentation times on constipation in mice. Shuidouchi is a short-time fermented soybean product....
This study compares the prevention effects of Shuidouchi with different fermentation times on constipation in mice. Shuidouchi is a short-time fermented soybean product. By improving its processing technology, it can incur better biological activity and become a health food. The Shuidouchi-treated mice were evaluated using constipation-related kits, quantitative polymerase chain reaction (qPCR), and Western blot assays. After the mice were fed 72-h-fermented Shuidouchi (72-SDC) for 9 d, the defecation time to excrete the first black stool was lower than that of the control and 24-SDC and 48-SDC groups, but was much higher than that of the normal group. The gastrointestinal (GI) transit of the small intestine of the 72-SDC group was higher than that of the control and the 24-SDC and 48-SDC groups, but lower that of the normal group. Meanwhile, 72-SDC could significantly increase the levels of , endothelin-1 (ET-1), vasoactive intestinal peptide (VIP), and acetylcholinesterase (AchE) in the serum of constipated mice compared to the levels in mice in the control group. Moreover, 72-SDC could raise , stem cell factor (), glial cell-derived neurotrophic factor (), neuronal nitric oxide synthase (), and endothelial nitric oxide synthase () messenger RNA (mRNA) and protein expression levels, and reduce transient receptor potential cation channel subfamily V member 1 () and inducible nitric oxide synthase () expression levels in small-intestinal tissue compared to the levels in the control group. Meanwhile, 72-SDC also raised mRNA expression in gastric tissue and transient receptor potential ankyrin 1 () mRNA expression in colon tissue compared to the control group mice; these effects were stronger than those of 24-SDC and 48-SDC. Shuidouchi has good preventative effects on constipation and performs best when fermented for at least 72 h.
PubMed: 30832248
DOI: 10.3390/foods8030086 -
Zhongguo Ying Yong Sheng Li Xue Za Zhi... Apr 2018To study the effects of Angelicaesinensis radix (Danggui) decoction on the therapeutic action and the colonic morphology and mucus secretion in XuexuBianmi model mice.
OBJECTIVE
To study the effects of Angelicaesinensis radix (Danggui) decoction on the therapeutic action and the colonic morphology and mucus secretion in XuexuBianmi model mice.
METHODS
Sixty Kunming mice, maleandfemaleinhalf, were randomly divided into six groups according to gender and weight (=10):normal control group, XuexuBianmi model group, positive control group, and high-dose, middle-dose and low-dose Danggui groups. Except the normal control group, the mice in the rest groups were orally administrated with diphenoxylate (DPN) and subcutaneously injected with acetylphenyhydrazine (APH) and intraperitoneally injected with cyclophosphamide (CPA) to copy XuexuBianmi model. Fromthe 14th day, the mice in Danggui groups were orally administered with different doses of Danggui decoction (16.67、8.33、4.17 g/kg), the mice in positive control group were orally administered with Changtongshu granule (5 g/kg), the mice in XuexuBianmi model group were administered with normal saline (NS) at the same volume (10 ml/kg), once a day for consecutive 28 days. The general status were observed, the first black defecation time (FBDT), the water content in stool and in colon in mice of all groups were tested. And the colon tissue was stained with hematoxylin-eosin (HE) and AB-PAS to observe the changes of colonic morphology and the mucus secretion.
RESULTS
Compared with the normal control group, there appeared the XuexuBianmi syndromes in model group as follows, the defecation time (FBDT) was significantly prolonged, the water contentinstool and in colon were decreased (<0.01), the colonic mucosa and gland were atrophied, mucous membrane layer was thinned (<0.01), mucus secretion was decreased. Compared with the XuexuBianmimodel group, the Xuexu and Bianmi syndromes were improved, the FBDT was significantly shortened (<0.05, <0.01), the water content of colon was increased in the three groups of Danggui decoction (<0.05, <0.01). The water content of the stool was obviouslyincreased in groups of 16.67and 8.33kg.dDanggui decoction (<0.05). The atrophy of colon mucosa and gland was improved, the mucus secretion was increased, and the colon lubrication function was improved in the three groups in different doses of Danggui decoction.
CONCLUSIONS
Dangguican improve the mucosal atrophy, and increase the secretion of colonic mucus, then the stool is softened and promoted to discharge.
Topics: Angelica sinensis; Animals; Colon; Drugs, Chinese Herbal; Mice; Mucus; Plant Roots
PubMed: 30788947
DOI: 10.12047/j.cjap.5616.2018.084 -
Food & Function Mar 2019Mulberry (Morus atropurpurea) has long been used to treat gastro-intestinal ailments; however, the functional basis of its therapeutic effects remains unclear. The aim...
Mulberry (Morus atropurpurea) has long been used to treat gastro-intestinal ailments; however, the functional basis of its therapeutic effects remains unclear. The aim of this study was to measure the effects of mulberry (administered by gavage) on diphenoxylate-induced constipation in mice and elucidate the mechanisms underlying these effects using constipation and physicochemical indexes, histological morphology and 16S rDNA amplicon analysis of fecal microbiota. Sixty Kunming mice were randomly divided into the following six groups (n = 10 per group): normal control, constipation model, positive control, and low-, mid- and high-dose mulberry groups. After 14 days of treatment, constipation was induced over 5 days and measurements were conducted. The results show that mulberry treatment prevented constipation by increasing the fecal water content, shortening the first red fecal defecation time, promoting gastric evacuation, and increasing the gastric-intestinal transit rate (P < 0.05). Compared with the constipation model group, the mulberry-treated groups showed decreased aquaporin gene expression (Aqp3, Aqp4, Aqp8 and Aqp9), decreased serum levels of inhibitory neurotransmitters (nitric oxide and vasoactive intestinal peptide) (P < 0.05), and increased serum levels of excitability neurotransmitters (acetyl choline, substance P, and motilin). The histological morphology of the colon showed that mulberry treatment increased the number of mucus cells (P < 0.05). Mulberry treatment also increased the concentrations of acetic, propionic, butyric, valeric and isovaleric acids (P < 0.05), increased the abundance of Lactobacillus and Bifidobacterium in feces, and decreased the abundance of Helicobacter and Prevotellaceae in feces. Our findings indicate that mulberry consumption effectively prevents constipation in mice and is a promising therapeutic candidate for constipation.
Topics: Animals; Constipation; Diphenoxylate; Fruit; Gastrointestinal Microbiome; Mice; Morus
PubMed: 30785176
DOI: 10.1039/c9fo00132h -
The Oncologist Aug 2019Patients with neuroendocrine tumors (NETs) and carcinoid syndrome experience considerable morbidity and mortality; carcinoid syndrome may be associated with shorter...
BACKGROUND
Patients with neuroendocrine tumors (NETs) and carcinoid syndrome experience considerable morbidity and mortality; carcinoid syndrome may be associated with shorter survival. Carcinoid syndrome is linked to tumoral secretion of serotonin and other bioactive substances. The subsequent debilitating diarrhea and urgency to defecate pose significant health risks. In previous studies, telotristat ethyl, a tryptophan hydroxylase inhibitor, was effective and well tolerated in treating carcinoid syndrome diarrhea. We present pooled safety data from five clinical trials with telotristat ethyl in patients with carcinoid syndrome.
SUBJECTS, MATERIALS, AND METHODS
Adverse events reported during telotristat ethyl treatment were pooled from two phase II and three phase III clinical trials in 239 patients with carcinoid syndrome. Long-term safety of telotristat ethyl and causes of hospitalization and death were reviewed; overall survival was estimated.
RESULTS
Mean (median; range) duration of exposure and follow-up was 1.3 years (1.1 years; 1 week to 5.7 years), with 309 total patient-years of exposure. Leading causes of hospitalization were gastrointestinal disorders or were related to the underlying tumor and related treatment. Survival estimates at 1, 2, and 3 years were 93%, 88%, and 77%. Nearly all deaths were due to progression or complication of the underlying disease; none were attributable to telotristat ethyl. There was one death in year 4.
CONCLUSION
Based on long-term safety data, telotristat ethyl is well tolerated and has a favorable long-term safety profile in patients with carcinoid syndrome.
IMPLICATIONS FOR PRACTICE
Carcinoid syndrome can cause persistent diarrhea, even in patients treated with somatostatin analogs. Across five clinical trials in patients with carcinoid syndrome, telotristat ethyl has been well tolerated and efficacious, providing clinicians with a new approach to help control carcinoid syndrome diarrhea, in addition to somatostatin analog therapy. By reducing the stool frequency in patients with carcinoid syndrome whose diarrhea is refractory to anticholinergics, such as loperamide and atropine/diphenoxylate, and somatostatin analog dose escalation, improvement in quality of life becomes an achievable goal.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Diarrhea; Female; Humans; Male; Malignant Carcinoid Syndrome; Middle Aged; Patient Safety; Phenylalanine; Pyrimidines; Randomized Controlled Trials as Topic; Retrospective Studies; Treatment Outcome
PubMed: 30651397
DOI: 10.1634/theoncologist.2018-0236 -
Pharmacy Practice 2018Because community pharmacists are the most accessible healthcare professionals, they are often involved in managing minor ailments within the community setting.
BACKGROUND
Because community pharmacists are the most accessible healthcare professionals, they are often involved in managing minor ailments within the community setting.
OBJECTIVE
This study evaluated the community pharmacists' history taking practice, medicine dispensing and advice in response to acute diarrhea.
METHODS
Authors conducted a simulated-patient study in 75 community pharmacies in Baghdad, Iraq from February to May 2015. The female simulated-patient complained of acute diarrhea that had lasted for one day and requested for medicine to treat her condition. After exiting each pharmacy, she then assessed the practices of the community pharmacists through the use of a specially designed checklist adopted with modifications from relevant guidelines. For history taking, a maximum total of eight was the highest obtainable score. Data collected was quantitatively analyzed and Mann-Whitney, Chi-square or Fishers exact tests were used at an alpha level of 0.05.
RESULTS
All of the 75 pharmacies visited were managed by professionally qualified pharmacists. The most common questions asked during history taking were number of diarrheal episodes (n=62; 82.7%); duration of symptoms (n=59; 78.7%) and presence of other diseases and if any drug had been taken (n=58; 77.3%). Female pharmacists had a higher total mean score (6.45, SD=1.33) for history taking when compared to their male counterparts (4.34, SD=2.13); p <0.001. Medicine combination of diphenoxylate HCl 2.5mg + atropine sulphate 0.025mg (n=34; 27.9%) was most frequently dispensed while the least was oral rehydration salt (n=1; 0.8%). Around 20% (n=15) of pharmacists dispensed antimicrobial agents. Over half (n=46; 61.3%) of pharmacists indicated the frequency of use on the medicine packet. Conversely, less than half (n=33; 44.0%) gave any advice on food and fluid intake.
CONCLUSIONS
Majority of the community pharmacists asked at least four questions while taking patient history and was very likely to recommend antidiarrheal medicines as first line treatment options. The authors recommend the development of a minimum standard of practice as well as enhanced training for Iraqi community pharmacists.
PubMed: 30637034
DOI: 10.18549/PharmPract.2018.04.1313 -
Addiction & Health Jan 2018To self-medicate substance dependence, many substance users consume herbal medicines delivered in herbal medicine shops which are prepared through non-standard methods...
BACKGROUND
To self-medicate substance dependence, many substance users consume herbal medicines delivered in herbal medicine shops which are prepared through non-standard methods using a variety of different materials. Hence, the present study was carried out aiming to investigate and analyze the content of such herbal medicines.
METHODS
Four herbal medicine shops were selected from each of the 22 zones of Tehran City, Iran, and a total of 95 samples were purchased. A package containing 6 types of medication that was advertised by a satellite TV channel, was also purchased. Using high-performance liquid chromatography (HPLC) method, the samples were analyzed in the laboratory to detect different types of materials.
FINDINGS
Among the samples, 23 and 72 samples were uncovered compressed pills (Dragon pills) and capsules filled with colored powders (handmade self-medicating substance dependence capsules), respectively. The package advertised in the satellite TV was prepared in 6 various forms. The most common substances present in all the samples were as follows: diphenoxylate, tramadol, opioids, acetaminophen, and codeine with values of 90%, 86%, 78%, 69%, and 68%, respectively. On average, 5 of the above mentioned substances were present in each sample; moreover, 63% of the samples contained 5 or more substances. In addition, 42 (41%) of the samples contained all the 5 main substances including opioids, codeine, tramadol, diphenoxylate, and acetaminophen.
CONCLUSION
The findings of this study showed that handmade capsules and pills used for self-medicating substance dependence and also medicines advertised in the satellite TV channels contain different amounts of opioids, amphetamine, benzodiazepines, tramadol, codeine, and other substances that cause problems for substance users who are going to abandon substance abuse.
PubMed: 30627381
DOI: 10.22122/ahj.v10i1.508