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International Journal of Clinical and... 2018Constipation is one of the most common gastrointestinal diseases in the world. This study was to investigate the effects of rhein on intestinal transmission and colonic...
Constipation is one of the most common gastrointestinal diseases in the world. This study was to investigate the effects of rhein on intestinal transmission and colonic electromyography and expression of aquaporin-3 (AQP3) in the colonic mucosa of mice with constipation. The mouse model of constipation was established using the compound diphenoxylate. The first defecation time, the number of stools in the initial 6 hours and the promoting rate of eosin were measured as the bowel transit function. The BL-420F system was used to compare changes in the myoelectrical signals in the colons of the mice. Immunohistochemical analysis was used to detect the expression of AQP3 in the colonic mucosa of mice. Rhein had an obvious effect on the first defecation time and the number of red stool in the initial 6 hours. The first defecation time is reduced, and the number of red stools in 6 hours and the promoting rate of the small intestine were significantly increased after the treatment of rhein. In the rhein group, the slow-wave frequency and slow-wave amplitude of colonic myoelectrical activity were increased, and the mean optical density of AQP3 in the colonic mucosa and the area of positive expression were decreased. In conclusion, rhein can improve motor function and colonic electromyography of constipation mice, and reduce expression of AQP3 in the colonic mucosa, thereby relieving the symptoms of constipation effectively.
PubMed: 31938147
DOI: No ID Found -
British Journal of Pharmacology Feb 2017
Topics: Amides; Angiotensin-Converting Enzyme Inhibitors; Atropine; Central Nervous System; Diphenoxylate; Drug Combinations; History, 20th Century; History, 21st Century; Humans; Peptides; Peptidyl-Dipeptidase A
PubMed: 28116748
DOI: 10.1111/bph.13683 -
PloS One 2016Using an atropine-diphenoxylate-induced slow transit constipation (STC) model, this study explored the effects of the total glucosides of paeony (TGP) in the treatment...
OBJECTIVES
Using an atropine-diphenoxylate-induced slow transit constipation (STC) model, this study explored the effects of the total glucosides of paeony (TGP) in the treatment of STC and the possible mechanisms.
STUDY DESIGN
A prospective experimental animal study.
METHODS
The constipation model was set up in rats with an oral gavage of atropine-diphenoxylate and then treated with the TGP. The volume and moisture content of the faeces were observed and the intestinal kinetic power was evaluated. Meanwhile, the colorimetric method and enzyme linked immunosorbent assay (ELISA) were employed to determine the changes of nitric oxide (NO), nitric oxide synthase (NOS), vasoative intestinal peptide (VIP) and the P substance (SP) in the serum, respectively. The protein expressions of c-kit and stem cell factor (SCF) were assessed by immunohistochemical analysis and western blot, respectively, and the mRNA level of c-kit was measured by a reverse transcription polymerase chain reaction (RT-PCR).
RESULTS
The TGP attenuated STC responses in terms of an increase in the fecal volume and moisture content, an enhancement of intestinal transit rate and the reduction of NO, NOS and VIP in the serum. In addition, the c-kit, a labeling of interstitial cells of Cajal (ICC) increased at both protein and mRNA levels. SCF, which serves as a ligand of c-kit also increased at protein level.
CONCLUSION
The analysis of our data indicated that the TGP could obviously attenuate STC through improving the function of ICC and blocking the inhibitory neurotransmitters such as NO, NOS and VIP.
Topics: Animals; Constipation; Disease Models, Animal; Female; Gastrointestinal Motility; Glucosides; Interstitial Cells of Cajal; Neurotransmitter Agents; Nitric Oxide; Nitric Oxide Synthase; Paeonia; Prospective Studies; Proto-Oncogene Proteins c-kit; Rats; Rats, Wistar; Stem Cell Factor; Substance P; Vasoactive Intestinal Peptide
PubMed: 27478893
DOI: 10.1371/journal.pone.0160398 -
Scientific Reports Jul 2016The purpose of this study was to investigate the prevalences of and association between nonmedical prescription opioid use (NMPOU) and sleep quality among Chinese high...
The purpose of this study was to investigate the prevalences of and association between nonmedical prescription opioid use (NMPOU) and sleep quality among Chinese high school students. A cross-sectional study was conducted in Chongqing high school students in 2012, and questionnaires from 18,686 students were completed and eligible for this study. Demographic and NMPOU information was collected using a self-administered questionnaire. The Chinese Pittsburgh Sleep Quality index (CPSQI) was used to assess the occurrence of poor sleep. Among the total sample, 18.0% were classified as poor sleepers (27.4% of the subjects with past-month NMPOU), and the prevalences of lifetime, past-year and past-month NMPOU were 14.6, 4.6 and 2.8% across the entire sample, respectively. The most commonly used medicine was licorice tablets with morphine (9.1, 2.5 and 1.5% for lifetime, past-year and past-month, respectively), followed by cough syrup with codeine, Percocet, diphenoxylate and tramadol. After adjustment for potential confounders, the association between past-month NMPOU and poor sleep remained significant (AOR = 1.47, 95% CI 1.17 to 1.85). Programs aimed at decreasing NMPOU should also pay attention to sleep quality among adolescents.
Topics: Adolescent; Analgesics, Opioid; Child; China; Cross-Sectional Studies; Drug Misuse; Female; Humans; Male; Odds Ratio; Prevalence; Risk Factors; Sleep Wake Disorders; Students; Young Adult
PubMed: 27467181
DOI: 10.1038/srep30411 -
Cancer Management and Research 2016Anaplastic lymphoma kinase (ALK) gene fusions occur in 3%-7% of non-small-cell lung cancer (NSCLC) cases. Ceritinib, a once-daily, oral ALK inhibitor, has activity...
Anaplastic lymphoma kinase (ALK) gene fusions occur in 3%-7% of non-small-cell lung cancer (NSCLC) cases. Ceritinib, a once-daily, oral ALK inhibitor, has activity against crizotinib-resistant and crizotinib-naïve NSCLC, including brain metastases. Ceritinib (Zykadia™) was granted accelerated approval by the US Food and Drug Administration in 2014 for treating crizotinib-resistant ALK-positive NSCLC. Adverse events (AEs), particularly gastrointestinal (GI) AEs, are commonly experienced at the recommended dose of 750 mg/d and ∼38% of patients require dose interruption or reduction for GI AEs. This case study details our experience with the use of proactive GI AE management regimens in patients treated with ceritinib (750 mg/d) across two study sites. Proactive Regimens A and B were implemented in patients with metastatic ALK-positive NSCLC treated with ceritinib to manage drug-related GI AEs. Regimen A comprised ondansetron and diphenoxylate/atropine or loperamide, taken 30 minutes prior to ceritinib dose. Regimen B included dicyclomine (taken with the first ceritinib dose), ondansetron (taken 30 minutes prior to ceritinib dose for the first seven doses), and loperamide (taken as needed with the onset of diarrhea). The proactive medications were tapered off depending on patient tolerability to ceritinib. Nine patient cases are presented. Starting Regimens A or B before the first dose of ceritinib, or as soon as GI symptoms were encountered, prevented the need for dose reduction due to GI toxicity in eight of the nine patients. Using these regimens, 78% of patients were able to remain on 750 mg/d fasting. Two patients received 23 months and 16 months of therapy and remain on ceritinib 750 mg/d and 600 mg/d, respectively. Although not currently recommended or implemented in clinical studies, based on the patients evaluated here, upfront or proactive treatment plans that address AEs early on can allow the majority of patients to remain on the approved 750 mg/d ceritinib dose.
PubMed: 27069372
DOI: 10.2147/CMAR.S96471 -
International Journal of Clinical and... 2015In order to investigate the effects of diphenoxylate on the metabolic capacity of cytochrome P450 (CYP) enzymes, a cocktail method was employed to evaluate the...
In order to investigate the effects of diphenoxylate on the metabolic capacity of cytochrome P450 (CYP) enzymes, a cocktail method was employed to evaluate the activities of CYP2B6, CYP2D6, CYP2C19, CYP1A2, CYP3A4, CYP2C9. The rats were randomly divided into diphenoxylate group (Low, Medium, High) and control group. The diphenoxylate group rats were given 12, 24, 48 mg/kg (Low, Medium, High) diphenoxylate by continuous intragastric administration for 7 days. Six probe drugs bupropion, metroprolol omeprazole, phenacetin, testosterone and tolbutamide were given to rats through intragastric administration, and the plasma concentrations were determined by UPLC-MS/MS. Statistical pharmacokinetics difference for omeprazole, phenacetin and tolbutamide in rats were observed by comparing diphenoxylate group with control group. Continuous 7 days-intragastric administration of diphenoxylate induces the activities of CYP2C19, CYP1A2 and CYP2C9 of rats. Induction of drug metabolizing enzyme by diphenoxylate would reduce the efficacy of other drug. Additionally, high dosage diphenoxylate may cause hepatotoxicity.
PubMed: 26770498
DOI: No ID Found -
Thyroid : Official Journal of the... Oct 2015Medullary thyroid cancer (MTC)-related diarrhea can be debilitating, reduces quality of life (QOL), and may be the only indication for initiating systemic therapy....
Efficacy of the Natural Clay, Calcium Aluminosilicate Anti-Diarrheal, in Reducing Medullary Thyroid Cancer-Related Diarrhea and Its Effects on Quality of Life: A Pilot Study.
INTRODUCTION
Medullary thyroid cancer (MTC)-related diarrhea can be debilitating, reduces quality of life (QOL), and may be the only indication for initiating systemic therapy. Conventional antidiarrheal drugs are not always helpful and may have side effects. Calcium aluminosilicate antidiarrheal (CASAD), a natural calcium montmorrilonite clay, safely adsorbs toxins and inflammatory proteins associated with diarrhea. It was hypothesized that CASAD would reduce the severity of diarrhea and improve QOL in MTC patients.
METHODS
This was a prospective pilot trial (NCT01739634) of MTC patients not on systemic therapy with self-reported diarrhea of three or more bowel movements (BMs) per day for a week or more. The study design included a one-week run-in period followed by one week of CASAD ± a two-week optional continuation period. The primary endpoint was efficacy of one week of CASAD treatment in decreasing the number of BMs per day by ≥20% when compared with the baseline run-in period. Secondary objectives included tolerability and safety and the impact on QOL using the MD Anderson Symptom Inventory-Thyroid questionnaire (MDASI-THY).
RESULTS
Ten MTC patients (median age = 52 years, 70% female, 80% white) were enrolled. All had distant metastases, and median calcitonin was 5088 ng/mL (range 1817-42,007 ng/mL). Ninety percent had received prior antidiarrheals, and 40% of these had used two or more drugs, including tincture of opium (30%), loperamide (50%), diphenoxylate/atropine (20%), colestipol (10%), or cholestyramine (10%). Of seven evaluable patients, four (56%) had ≥20% reduction in BMs per day. Six out of seven patients discontinued their prior antidiarrheals. Best response ranged from 7% to 99% reduction in mean BMs/day from baseline. Five out of seven patients considered CASAD a success, and they opted for the two-week continuation period. Improvements in diarrhea and all six interference items assessed by MDASI-THY were noted at weeks 1 and 3. Total interference score was significantly improved at three weeks compared with baseline (p = 0.05). An oral levothyroxine absorption test was performed in one patient; malabsorption of levothyroxine was not observed. Adverse events included flatulence (40%), bloating (10%), heartburn (10%), and constipation (10%).
CONCLUSIONS
CASAD is a promising strategy for treatment of MTC-related diarrhea. In this small pilot study, improvements in frequency and quality of diarrhea as well as QOL were noted. Further studies in this population are warranted.
Topics: Adult; Aged; Aluminum Silicates; Antidiarrheals; Carcinoma, Medullary; Clay; Diarrhea; Female; Humans; Male; Middle Aged; Pilot Projects; Prospective Studies; Quality of Life; Thyroid Neoplasms; Treatment Outcome
PubMed: 26200040
DOI: 10.1089/thy.2015.0166 -
Annals of Gastroenterology 2015Chronic watery diarrhea combined with normal-appearing colonic mucosa at endoscopy with abnormal histopathology is classified as microscopic colitis. Microscopic colitis...
Chronic watery diarrhea combined with normal-appearing colonic mucosa at endoscopy with abnormal histopathology is classified as microscopic colitis. Microscopic colitis encompasses both collagenous and lymphocytic colitis. A 42-year-old Caucasian woman presented with severe diarrhea for six weeks with loose watery stools every 1-2 h, approximately 15 episodes per day. She denied any melena or significant abdominal pain. She denied nonsteroidal anti-inflammatory drug or lansoprazole use, and was only taking diphenoxylate/atropine for her symptoms. Colonoscopy revealed superficial ulcerations in the distal ascending and transverse colon and scattered ulcerations in the descending and sigmoid colon, with biopsy confirming collagenous colitis. We report a rare case of collagenous colitis accompanied by mucosal ulcerations in the absence of known culprits of mucosal ulcerations, such as nonsteroidal anti-inflammatory drugs or lansoprazole.
PubMed: 26130218
DOI: No ID Found -
The Cochrane Database of Systematic... May 2015Agitation is a common experience for people living with dementia, particularly as day-to-day function and cognition start to decline more. At the present time there are... (Review)
Review
BACKGROUND
Agitation is a common experience for people living with dementia, particularly as day-to-day function and cognition start to decline more. At the present time there are limited pharmacological options for relieving agitation and little is known about the safety and efficacy of opioid drugs in this setting.
OBJECTIVES
To determine the clinical efficacy and safety of opioids for agitation in people with dementia.
SEARCH METHODS
We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group Specialized Register, on 13 June 2014 using the terms: narcotic OR opioid OR opium OR morphine OR buprenorphine OR codeine OR dextromoramide OR diphenoxylate OR dipipanone OR dextropropoxyphene OR propoxyphene OR diamorphine OR dihydrocodeine OR alfentanil OR fentanyl OR remifentanil OR meptazinol OR methadone OR nalbuphine OR oxycodone OR papaveretum OR pentazocine OR meperidine OR pethidine OR phenazocine OR hydrocodone OR hydromorphone OR levorphanol OR oxymorphone OR butorphanol OR dezocine OR sufentanil OR ketobemidone.ALOIS contains records of clinical trials identified from monthly searches of a number of major healthcare databases such as MEDLINE, EMBASE and PscyINFO, as well as numerous trial registries and grey literature sources.
SELECTION CRITERIA
Randomised, controlled trials of opioids compared to placebo for agitation in people with dementia.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed the studies identified by the search against the inclusion criteria.
MAIN RESULTS
There are currently no completed randomised, placebo controlled trials of opioids for agitation in dementia. There are two potentially relevant trials still in progress.
AUTHORS' CONCLUSIONS
We found insufficient evidence to establish the clinical efficacy and safety of opioids for agitation in people with dementia. There remains a lack of data to determine if or when opioids either relieve or exacerbate agitation. More evidence is needed to guide the effective, appropriate and safe use of opioids in dementia.
Topics: Analgesics, Opioid; Dementia; Humans; Psychomotor Agitation
PubMed: 25972091
DOI: 10.1002/14651858.CD009705.pub2 -
Toxicology Reports 2015Liquid-liquid extraction (LLE) is the most commonly sample preparation procedure used by forensic toxicologists in China for screening drugs in whole human blood. It...
Liquid-liquid extraction (LLE) is the most commonly sample preparation procedure used by forensic toxicologists in China for screening drugs in whole human blood. It extracts numerous substances from blood including targeted drugs and interfering substances, specifically triglycerides (TG). With increasing prevalence of hyperlipidemia, the influences of TG on LLE and on subsequent analysis with gas chromatography-mass spectrometry (GC-MS) may become a major issue for forensic laboratories. This study aims to elucidate the influences of TG on LLE and to provide possible solutions to this problem. Nineteen commonly encountered drugs in forensic cases were spiked to human whole blood with different TG concentrations. Diethyl ether, ethyl acetate/hexane mixed solutions, chlorobutane and several other frequently used solvents were tested for the extraction of drugs from spiked whole blood. The supernatant organic layer was evaporated to dryness and reconstituted with methanol. The resultant products were analyzed by GC-MS, and the extraction recovery was calculated. LLE with diethyl ether, ethyl acetate/hexane (9:1) and chlorobutane all possessed effective and reliable extraction recoveries for blood sample with low TG concentrations (0.63-6.85 mmol/L). At high TG concentrations, diethyl ether produced a highly turbid substance that could not be further analyzed using GC-MS. Extraction recoveries drastically dropped for ethyl acetate/hexane (9:1) mixture at high TG concentrations, while chlorobutane experienced minimal drops in extraction recoveries. In conclusion, TG levels in whole blood noticeably influence drug recovery to variable extents depending on the LLE solvent. Chlorobutane showed minimal influences from TG content in whole blood and thus is the recommended LLE solvent for forensic drug extraction.
PubMed: 28962414
DOI: 10.1016/j.toxrep.2015.02.006