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Zhonghua Liu Xing Bing Xue Za Zhi =... Sep 2018To investigate the prevalence of diphenoxylate abuse and related factors of forced drug abstainer in Gansu province. By using a self-designed questionnaire, an...
To investigate the prevalence of diphenoxylate abuse and related factors of forced drug abstainer in Gansu province. By using a self-designed questionnaire, an epidemiologic investigation was carried out among 2 108 forced drug abstainer selected from the compulsory isolation detoxification center of Gansu province. A case-control study was conducted to analyze the factors related with diphenoxylate abuse. The diphenoxylate abuse rate among forced drug abstainer in Gansu was 19.8 (406/2 046), ranking first in medical drug abuse. Multiple logistic regression analysis showed that factors as relieving withdrawal symptoms (=2.08, 95: 1.01- 4.32), ways to obtain diphenoxylate (other ways: =1.00; regular clinic: =27.67, 95: 2.64-289.82; friend: =0.01, 95: 0.01-0.03), degree of euphoria (high: =1.00; medium: =3.36, 95: 1.18-9.55; low: =26.16, 95: 10.30-66.42), years of drug abuse (<5 years: =1.00; 10-15 years: =2.48, 95: 1.02-6.04), abuse at home or in friend's house (=3.04, 95: 1.08-8.68), abuse in car (=0.05, 95: 0.00-0.68) and detoxification for the first time (=0.61, 95: 0.43-0.86) were the possible influencing factors for diphenoxylate abuse. The prevalence of diphenoxylate abuse in forced drug abstainer in Gansu was relatively high. Reasons of abusing, the way to obtain diphenoxylate, whether using drug together with friends, degree of euphoria, years of abuse, abuse place and times for detoxification were related factors influencing the abuse of diphenoxylate.
Topics: Analgesics, Opioid; Case-Control Studies; China; Diphenoxylate; Humans; Substance Withdrawal Syndrome; Substance-Related Disorders; Surveys and Questionnaires
PubMed: 30293314
DOI: 10.3760/cma.j.issn.0254-6450.2018.09.015 -
Zhen Ci Yan Jiu = Acupuncture Research Jul 2023To observe the effect of acupuncture of "Tianshu"(ST25) at different depths on colonic transportation function, expressions of colonic substance P (SP) and interstitial...
OBJECTIVE
To observe the effect of acupuncture of "Tianshu"(ST25) at different depths on colonic transportation function, expressions of colonic substance P (SP) and interstitial cells of Cajal (ICC) in rats with slow transit constipation (STC), so as to explore its mechanisms underlying improvement of STC..
METHODS
Fifty male Wistar rats were selected and randomly divided into control,STC model,conventional acupuncture,deep needling group 1 and deep needling group 2 groups,with 10 rats in each group.The STC model was established by gavage of 1 mg/mL compound diphenoxylate suspension (10 mg/kg), once every other day for 21 days, and rats of the control group were given the same dose of distilled water by gavage.EA (2 Hz, 2 mA) was applied to "Tianshu"(ST25), with the acupuncture needle inserted to a depth of 3 mm for rats of the conventional acupuncture group, 4.5 mm for those of deep needling group 1, and 10 mm for those of the deep needling group 2. The acupuncture needle was twirled for 1 min, then retained for 15 min each time, once a day for 15 consecutive days.Following modeling, rats of the 4 groups and the control group received gavage of active carbon 2 mL (100 g/L) for observing the excretion time of the first black stool grain to assess the intestinal transit function. The colonic myoelectric activities (frequency and amplitude) were recorded by using BIOPAC multichannel physiograph. The immunoactivity of SP and c-kit (a transmembrane protein kinase for identification of ICC) of colonic musculature was detected by immunohistochemistry.
RESULTS
Compared with the control group,the time of excretion of the first black stool grain, and the amplitude of colonic electromyogram (EMG) were significantly increased (<0.01), while the frequency of EMG, expressions of SP and c-kit (ICC) were significantly decreased in the model group (<0.01). In contrast to the model group, both deep needling group 1 and 2 had a decrease in the time of excretion of the first black stool grain, and amplitude of intestinal EMG, and an increase of frequency of intestinal EMG, and immunoactivity of SP and c-kit (<0.01). The effect of deep needling 2 is superior to that of deep needling 1 in reducing the time of excretion of the first black stool grain (<0.05), lowering the amplitude of EMG of the gut smooth muscle (<0.05) and in increasing the frequency of EMG (<0.05) and the expressions of SP and c-kit (<0.05). No significant changes were found in the levels of frequency and amplitude of EMG, and expressions of SP and c-kit after routine needling in comparison with the model group (>0.05), except the excretion time of the first black stool grain (<0.05).
CONCLUSION
Deep needling at ST25 at depth of 4.5 mm and 10 mm,especially at depth of 10 mm,has a significant effect in promoting gut motility to ameliorate constipation in rats with STC, which may be related to its function in up-regulating the expressions of SP and ICC activity.
Topics: Animals; Male; Rats; Acupuncture Points; Colon; Constipation; Defecation; Proto-Oncogene Proteins c-kit; Rats, Wistar; Substance P
PubMed: 37518957
DOI: 10.13702/j.1000-0607.20220588 -
Journal of Biosciences 2021Slow transit constipation (STC) is a gastrointestinal disorder characterized by abnormal prolonged colonic transit time, which affects the life quality of many people....
Slow transit constipation (STC) is a gastrointestinal disorder characterized by abnormal prolonged colonic transit time, which affects the life quality of many people. The decrease number of interstitial cells of Cajal (ICCs) is involved in the pathogenesis of STC. However, the molecular mechanism of loss of ICCs in STC remains unclear, making it difficult to develop new agents for the disease. In this study, we investigated the mechanism of decreasing ICCs in the pathogenesis of STC. We constructed the STC model rats by using atropine and diphenoxylate. A series of methods were used including immunofluorescence and immunochemistry staining, western blot, qRT-PCR, exosomes extraction and exosomes labeling. The results indicate that ICCs decreased in the STC rats accompanied with the macrophages activation. Further studies suggested that macrophages decreased the cell viability of ICCs by secretion exosomes containing miR-34c-5p. miR-34c5p targeted the 3Ꞌ -UTR of stem cell factor(SCF) mRNA and regulated the expression of SCF negatively. In conclusion, we demonstrated a novel regulatory mechanism of ICCs cell viability in STC. We found that exosome miR-34c-5p mediate macrophage-ICCs cross-talk. M1 macrophages derived exosomes miR-34c-5p decreased ICCs cell viability by directly targeting SCF.
Topics: Analgesics, Opioid; Animals; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Atropine; Cell Survival; Constipation; Diphenoxylate; Exosomes; Gastrointestinal Motility; Gene Expression Regulation; Interstitial Cells of Cajal; Macrophages; MicroRNAs; Muscarinic Antagonists; Proto-Oncogene Proteins c-kit; RNA, Messenger; Rats; Rats, Sprague-Dawley; Stem Cell Factor
PubMed: 34544909
DOI: No ID Found -
Antimicrobial Agents and Chemotherapy May 2024Cell culture-based screening of a chemical library identified diphenoxylate as an antiviral agent against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)....
Cell culture-based screening of a chemical library identified diphenoxylate as an antiviral agent against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The observed 50% effective concentrations ranged between 1.4 and 4.9 µM against the original wild-type strain and its variants. Time-of-addition experiments indicated that diphenoxylate is an entry blocker targeting a host factor involved in viral infection. Fluorescence microscopic analysis visualized that diphenoxylate prevented SARS-CoV-2 particles from penetrating the cell membrane and also impaired endo-lysosomal acidification. Diphenoxylate exhibited a synergistic inhibitory effect on SARS-CoV-2 infection in human lung epithelial Calu-3 cells when combined with a transmembrane serine protease 2 (TMPRSS2) inhibitor, nafamostat. This synergy suggested that efficient antiviral activity is achieved by blocking both TMPRSS2-mediated early and endosome-mediated late SARS-CoV-2 entry pathways. The antiviral efficacy of diphenoxylate against SARS-CoV-2 was reproducible in a human tonsil organoids system. In a transgenic mouse model expressing the obligate SARS-CoV-2 receptor, human angiotensin-converting enzyme 2, intranasal administration of diphenoxylate (10 mg/kg/day) significantly reduced the viral RNA copy number in the lungs by 70% on day 3. This study underscores that diphenoxylate represents a promising core scaffold, warranting further exploration for chemical modifications aimed at developing a new class of clinically effective antiviral drugs against SARS-CoV-2.
PubMed: 38742905
DOI: 10.1128/aac.00341-24 -
Drug Design, Development and Therapy 2021The naturally fermented yak yogurt of pastoralists in the Tibetan Plateau, China, because of its unique geographical environment and the unique lifestyle of Tibetan...
AIM
The naturally fermented yak yogurt of pastoralists in the Tibetan Plateau, China, because of its unique geographical environment and the unique lifestyle of Tibetan pastoralists, is very different from other kinds of sour milk, and the microorganisms it contains are special. subsp. HFY14 (LLSL-HFY14) is a new lactic acid bacterium isolated from naturally fermented yak yogurt. The purpose of this study was to study the inhibitory effect of the bacterium on constipation.
METHODS
Constipation was induced in ICR mice with diphenoxylate, and the constipated mice were treated with LLSL-HFY14. The weight and feces of the mice were visually detected. Colonic tissues were observed on hematoxylin and eosin-stained sections. Serum indices were detected with kits. mRNA expression in the colon was determined by quantitative polymerase chain reaction assay.
RESULTS
Constipation caused weight loss, the number of defecation granules, defecation weight, fecal water content decreased, and the first black stool excretion time increased. LLSL-HFY14 alleviated these symptoms, and the effects were similar to those of lactulose (drug). The pathological examination revealed that constipation caused pathological changes in the colon, and LLSL-HFY14 effectively alleviated the disease. LLSL-HFY14 increased serum levels of motilin, gastrin, endothelin, substance P, acetylcholinesterase, and vasoactive intestinal peptide (VIP) and decreased serum levels of somatostatin in constipated mice. In addition, LLSL-HFY14 upregulated VIP, cAMP, protein kinase A, and aquaporin 3 expression in colonic tissues of constipated mice in a dose-dependent manner.
CONCLUSION
LLSL-HFY14 inhibited constipation, similar to lactulose, and has the potential to become a biological agent.
Topics: Animals; Aquaporin 3; Cattle; Constipation; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Diphenoxylate; Disease Models, Animal; Female; Lactococcus lactis; Mice; Mice, Inbred ICR; Probiotics; Signal Transduction; Somatostatin; Vasoactive Intestinal Peptide; Yogurt
PubMed: 34007157
DOI: 10.2147/DDDT.S309675 -
Journal of Agricultural and Food... Aug 2023Veterinary drug residues present in foods can pose severe health threats to the population. The present study aims to develop a high-resolution mass spectral library of...
Veterinary drug residues present in foods can pose severe health threats to the population. The present study aims to develop a high-resolution mass spectral library of 158 veterinary drugs of 16 different classes for their rapid identification in food samples through liquid chromatography-high-resolution electrospray ionization-tandem mass spectrometry (LC-HR-ESI-MS/MS). Standard drugs were pooled according to their log values and exact masses before analysis. Spectra were collected at system automated collision energy, i.e., of 25-60 eV and four predetermined collision energies (10, 20, 30, and 40 eV) for each compound using a schedule precursor list of [M + H], [M + Na], and [M + NH] ions. The utility of the developed database was checked by analyzing food samples. A total of 17 veterinary drugs based on the reference standard retention times (RTs), HR-MS spectra, and MS/MS spectra were identified in the analyzed samples. Moreover, five veterinary drugs were selected for quantitative analysis, including doxycycline hyclate, lincomycin, sulfasalazine, moxifloxacin, and diphenoxylate, using liquid chromatography-ion trap mass-spectrometry (LC-IT-MS). Concentrations of the drug were obtained to vary from 0.0805 to 0.9731 mg/kg in food samples and were found to be exceeded in most of the cases as per the maximum residue levels described by Food and Agriculture Organization (FAO)/World Health Organization (WHO). The MS data were submitted to the MetaboLights online database (MTBLS2914). This study will help in the high-throughput screening of multiclass veterinary drugs in foodstuffs.
Topics: Tandem Mass Spectrometry; Spectrometry, Mass, Electrospray Ionization; Veterinary Drugs; Gas Chromatography-Mass Spectrometry; Chromatography, Liquid; Ions; Chromatography, High Pressure Liquid
PubMed: 37528805
DOI: 10.1021/acs.jafc.3c03715 -
Journal of Agricultural and Food... Jul 2020Three new flavonoids, quercetin-3--6-[methyl-()-3-hydroxy-3-methylglutaroyl(1→6]-β-d-glucopyranoside (),...
Three new flavonoids, quercetin-3--6-[methyl-()-3-hydroxy-3-methylglutaroyl(1→6]-β-d-glucopyranoside (), kaempferol-3--[methyl-()-3-hydroxy-3-methylglutaroyl(1→6)]-β-d-glucopyranoside (), and quercetin-3--6-[()-4-methoxy-5-methylhexa-2,4-dienoatyl(1→6)]-β-d-glucopyranoside (), and two new alkaloids, 5-dehydroxymethyl-pyrrolemarumine 4″--α-l-rhamnopyranoside () and -methyl--((4--α-l-rhamnopyranoside)benzyl) oxalamide (), together with 45 known compounds (-) were isolated from the leaves of Lam. Among those compounds, 1-octacosanol (), a straight-chain 28-carbon alcohol, exhibited good activity against diphenoxylate-induced constipation in mice, which is obtained as a laxative constituent from the plant for the first time. In order to have an accurate understanding of the content of compound , a quantification with gas chromatography-tandem mass spectrometry (GC-MS/MS) was carried out. The anti-inflammatory and α-glucosidase inhibitory activity of some compounds also was assessed.
Topics: Flavonoids; Gas Chromatography-Mass Spectrometry; Laxatives; Moringa oleifera; Plant Extracts; Plant Leaves
PubMed: 32631058
DOI: 10.1021/acs.jafc.0c01564 -
Oxidative Medicine and Cellular... 2022The - (ZhiShi, ZS-) (BaiZhu, BZ) pairs are often found in herbal formulas for constipation. The volatile oils of ZS and BZ (ZBVO) have good pharmacological activity...
BACKGROUND
The - (ZhiShi, ZS-) (BaiZhu, BZ) pairs are often found in herbal formulas for constipation. The volatile oils of ZS and BZ (ZBVO) have good pharmacological activity against constipation, but the mechanism for treatment of slow transit constipation (STC) remains unclear.
METHOD
A rat model using diphenoxylate tablets was constructed to investigate if transdermal administration of ZBVO would mediate intestinal microorganisms and fecal metabolites and improve STC symptoms. The regulatory effects of ZBVO at 0.15, 0.30, and 0.60 mL kg d on STC rats were assessed by measuring fecal water content, intestinal propulsion rate, histopathology, expression of gastrointestinal hormones, brain and intestinal peptides, and inflammatory factors. The changes in intestinal flora of STC rats were analyzed by 16S rRNA gene sequencing. Moreover, the untargeted fecal metabolomics analysis was performed by ultraperformance liquid chromatography quadrupole time-of-flight mass spectrometer (UPLC-Q-TOF-MS) technology.
RESULTS
The results showed that ZBVO had a modulating effect on STC by increasing the fecal water content and intestinal propulsion rate. Transdermal administration of ZBVO decreased serum levels of interleukin 6 (IL-6) and tumor necrosis factor- (TNF-) and increased the levels of gastrin (GAS) and substance P (SP). In addition, ZBVO increased 5-hydroxytryptamine (5-HT) levels and decreased vasoactive intestinal peptide (VIP) levels in colon and hippocampus tissues. The results of intestinal microbiota showed that ZBVO improved the diversity and abundance of intestinal microbiota and changed the community composition by decreasing and increasing , , and . And the feces metabolomics found that nicotinate and nicotinamide metabolism, purine metabolism, citrate cycle (TCA cycle), pyruvate metabolism, arachidonic acid metabolism, pyrimidine metabolism, and primary bile acid biosynthesis were modulated.
CONCLUSION
These findings suggest that ZBVO can alleviate STC symptoms by promoting intestinal peristalsis, increasing fecal water content, regulating gastrointestinal hormone level, reducing the inflammatory response, and regulating brain and intestinal peptides after transdermal administration. And structural changes in the intestinal microbiota are closely related to host metabolism and intestinal microbiota destroyed in STC modeling could be significantly improved by the ZBVO, which provides a reference for the development of aromatic drug macrohealth products.
Topics: Administration, Cutaneous; Animals; Citrus; Constipation; Disease Models, Animal; Gastrointestinal Microbiome; Metabolomics; Oils, Volatile; Rats; Rats, Sprague-Dawley
PubMed: 35087623
DOI: 10.1155/2022/9965334 -
Progress in Transplantation (Aliso... Mar 2017Norovirus is a common self-limiting gastrointestinal infection, but in transplant recipients, symptoms can last for months and result in serious health complications. As...
Norovirus is a common self-limiting gastrointestinal infection, but in transplant recipients, symptoms can last for months and result in serious health complications. As there is currently no established treatment for chronic norovirus infection in transplant patients, management has been directed at symptom control, trial of various antivirals, and ultimately reductions in immunosuppression. We present 3 cases of chronic norovirus infection in cardiac transplant patients to illustrate various approaches to diagnosis, the prolonged nature of disease symptoms, and treatment options. When managing a transplant recipient with chronic diarrhea, considering a broad differential as well as maintaining a high suspicion for infectious etiologies is key. A stepwise approach to management includes termination of diarrhea-causing medications, trials of nitazoxanide and immunoglobulin, and reductions in immunosuppressive therapies. Although brief discontinuation of immunosuppression is often required to achieve symptom, graft rejection is often a complication.
Topics: Adult; Antidiarrheals; Atropine; Caliciviridae Infections; Chronic Disease; Diphenoxylate; Drug Combinations; Female; Gastrointestinal Agents; Heart Transplantation; Humans; Immunosuppressive Agents; Loperamide; Male; Middle Aged; Polymerase Chain Reaction; Transplant Recipients
PubMed: 27881814
DOI: 10.1177/1526924816679843 -
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