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Luminescence : the Journal of... Jun 2024In this study, a chemiluminescence (CL) method was developed to determine diphenoxylate in tablets and human plasma. This is the first CL method proposed to determine...
In this study, a chemiluminescence (CL) method was developed to determine diphenoxylate in tablets and human plasma. This is the first CL method proposed to determine diphenoxylate. Creating three-dimensional data caused the parallel factor analysis algorithm (PARAFAC) to be used for the first time in CL methods. The method is based on the fact that diphenoxylate enhances the weak CL produced in the reaction of Ru(phen) and acidic Ce(IV), and the concentration of Ce(IV) solution has a different effect on the CL response of diphenoxylate and the blank plasma. The calibration curve was linear from 4.0 × 10 to 1.6 × 10 mol L (R = 0.9954), and the detection limit was 1.3 × 10 mol L (S/N = 3). The sampling rate was about 30 samples per hour, and the % RSD for 10 repeated measurements of 4 × 10 mol L diphenoxylate was 5.4%. The interference effects of some ions, amino acids, and common additives were also investigated. The CL method was successfully used to determine diphenoxylate in tablets, and the results were statistically confirmed by the reference method. The proposed CL method and the PARAFAC algorithm were successfully used to determine the concentration of diphenoxylate in human blood plasma samples.
Topics: Humans; Tablets; Luminescent Measurements; Luminescence; Limit of Detection; Algorithms; Oxalates; Factor Analysis, Statistical
PubMed: 38859619
DOI: 10.1002/bio.4805 -
Advances in Clinical and Experimental... May 2024Liqi Tongbian is a traditional Chinese medicine (TCM) preparation that contains herbs that may treat slow transit constipation (STC). Atractylodes macrocephala,...
BACKGROUND
Liqi Tongbian is a traditional Chinese medicine (TCM) preparation that contains herbs that may treat slow transit constipation (STC). Atractylodes macrocephala, Astragalus membranaceus, Fructus aurantii, radish seed, uncooked Polygonum multiflorum, and Agastache rugosa were included in the formula for their unique qualities. The control of water transfer in the colon is greatly influenced by aquaporin 3 (AQP3).
OBJECTIVES
Based on this, the Liqi Tongbian mixture was used to detect the concentrations of aquaporins (AQPs), 5-HT and nitrix oxide synthase 1 (NOS1) in STC rats, and explore its effect, in order to provide a theoretical basis for the remedy of STC with TCM.
MATERIAL AND METHODS
Zhejiang University of Traditional Chinese Medicine provided 32 three-week-old Sprague Dawley rats of SPF-grade. The pairs licensed under SYXK (Zhejiang) 2021-0012 were kept at 20-25°C and humidity of 50-65%. The compound diphenoxylate caused constipation in the control, model, Liqi laxative (LQTB), and mosapride groups. The Liqi laxative rats were administered a mixture of traditional Chinese herbs after modeling, while mosapride was given to the other group. The levels of 5-HT, NOS1 and AQPs were tested in the feces and intestinal tissues.
RESULTS
Comparing the condition of rat feces, it was found that the model group had significantly lower overall bulk, score and particles within 24 h compared to the control group. In comparison to mosapride, LQTB performed better. The model group had higher levels of 5-HT and NOS1 in intestinal tissue, while the LQTB and mosapride groups had decreased levels of these AQPs. LQTB had lower levels of AQP1, AQP3 and AQP4 than mosapride, while the model group had higher levels of these AQPs.
CONCLUSIONS
Liqi Tongbian mixture works better than mosapride in improving constipation symptoms in rats with STC, and its mechanism is related to regulating the level of intestinal AQPs and neurotransmitters.
PubMed: 38819938
DOI: 10.17219/acem/175808 -
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 -
Nan Fang Yi Ke Da Xue Xue Bao = Journal... Apr 2024To explore the therapeutic effect of transdermal patches containing Cassia seed extract applied at the navel on slow transit constipation (STC) in rats and explore the...
[Transdermal patches containing Cassia seed extract applied at the navel for slow transit constipation in rats: therapeutic effect and analysis of the spectrum-effect relationship].
OBJECTIVE
To explore the therapeutic effect of transdermal patches containing Cassia seed extract applied at the navel on slow transit constipation (STC) in rats and explore the spectrum-effect relationship of the patches.
METHOD
In a STC rat model established by gavage of compound diphenoxylate suspension for 14 days, the transdermal patches containing low, medium and high doses of Cassia seed extract (41.75, 125.25, and 375.75 mg/kg, respectively) were applied at the Shenque acupoint on the abdomen for 14 days after modeling, with constipation patches (13.33 mg/kg) as the positive control. After the treatment, fecal water content and intestinal propulsion rate of the rats were calculated, the pathological changes in the colon were observed with HE staining. Serum NO and NOS levels and the total protein content and NO, NOS and AChE expressions in the colon tissue were determined. HPLC fingerprints of the transdermal patches were established, and the spectrum-effect relationship between the common peaks of the patches and its therapeutic effect were analyzed.
RESULTS
Treatment with the transdermal patches containing Cassia seed extract significantly increased fecal water content and intestinal propulsion rate of the rat models, where no pathological changes in the colon tissue were detected. The treatment also suppressed the elevations of serum and colonic NO and NOS levels and reduction of AChE in STC rats. Twenty-eight common peaks were confirmed in the HPLC fingerprints of 6 batches of Cassia seed extract-containing patches. Analysis of the spectrum-effect relationship showed that autrantio-obtusin had the greatest contribution to the therapeutic effect of the patches in STC rats.
CONCLUSION
The Cassia seed extract-containing patches alleviates STC in rats via synergistic actions of multiple active ingredients in the extract, where autrantio-obtusin, rhein, chrysoobtusin, obtusin, obtusifolin, emodin, chrysophanol, and physcion are identified as the main active ingredients.
Topics: Animals; Rats; Cassia; Constipation; Seeds; Transdermal Patch; Plant Extracts; Rats, Sprague-Dawley; Colon; Acupuncture Points; Nitric Oxide; Disease Models, Animal; Male; Drugs, Chinese Herbal
PubMed: 38708506
DOI: 10.12122/j.issn.1673-4254.2024.04.14 -
Ulusal Travma Ve Acil Cerrahi Dergisi =... Apr 2024Following extended colon resections, it may not always be possible to perform colorectal anastomosis. The Deloyers procedure, which involves the transposition of the... (Review)
Review
Following extended colon resections, it may not always be possible to perform colorectal anastomosis. The Deloyers procedure, which involves the transposition of the right colon, has been identified as a viable solution. This report aims to discuss the circumstances under which the Deloyers procedure was performed, as well as to evaluate the early and late postoperative outcomes, by reviewing cases conducted between 2010 and 2023. In a 22-year-old female patient who suffered major organ and tissue loss (with injuries to the sigmoid colon, descending colon, transverse colon, and mesentery) due to a firearm injury, the Deloyers procedure was applied during restorative surgery following initial damage control surgery. The procedure involved mobilizing the cecum and right colon, performing a cranio-caudal rotation over the ileocolic artery pedicle, followed by an appendectomy, and creating a colorectal anastomosis using circular staplers. There were no complications during the postoperative follow-ups. By the 14th postoperative day, the patient was discharged and experienced bowel movements four times a day, managed with 2.5 mg of diphenoxylate hydrochloride and 0.025 mg of atropine sulfate. At the 6-month follow-up, the frequency of bowel movements had decreased to twice daily without the need for medical treatment. Given the functional outcomes in patients after extended left colectomies, the Deloyers procedure, with its low associated morbidity, stands out as a viable option.
Topics: Female; Humans; Young Adult; Adult; Firearms; Wounds, Gunshot; Anastomosis, Surgical; Colorectal Neoplasms
PubMed: 38634843
DOI: 10.14744/tjtes.2024.20813 -
The Kaohsiung Journal of Medical... Jun 2024Slow transit constipation (STC) is one of the most common gastrointestinal disorders in children and adults worldwide. Paeoniflorin (PF), a monoterpene glycoside...
Slow transit constipation (STC) is one of the most common gastrointestinal disorders in children and adults worldwide. Paeoniflorin (PF), a monoterpene glycoside compound extracted from the dried root of Paeonia lactiflora, has been found to alleviate STC, but the mechanisms of its effect remain unclear. The present study aimed to investigate the effects and mechanisms of PF on intestinal fluid metabolism and visceral sensitization in rats with compound diphenoxylate-induced STC. Based on the evaluation of the laxative effect, the abdominal withdrawal reflex test, enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry were used to detect the visceral sensitivity, fluid metabolism-related proteins, and acid-sensitive ion channel 3/extracellular signal-regulated kinase (ASIC3/ERK) pathway-related molecules. PF treatment not only attenuated compound diphenoxylate-induced constipation symptoms and colonic pathological damage in rats but also ameliorated colonic fluid metabolic disorders and visceral sensitization abnormalities, as manifested by increased colonic goblet cell counts and mucin2 protein expression, decreased aquaporin3 protein expression, improved abdominal withdrawal reflex scores, reduced visceral pain threshold, upregulated serum 5-hydroxytryptamine, and downregulated vasoactive intestinal peptide levels. Furthermore, PF activated the colonic ASIC3/ERK pathway in STC rats, and ASIC3 inhibition partially counteracted PF's modulatory effects on intestinal fluid and visceral sensation. In conclusion, PF alleviated impaired intestinal fluid metabolism and abnormal visceral sensitization in STC rats and thus relieved their symptoms through activation of the ASIC3/ERK pathway.
Topics: Animals; Glucosides; Monoterpenes; Acid Sensing Ion Channels; Constipation; Rats; Male; MAP Kinase Signaling System; Rats, Sprague-Dawley; Colon; Gastrointestinal Transit; Aquaporin 3; Serotonin; Visceral Pain
PubMed: 38634140
DOI: 10.1002/kjm2.12829 -
International Journal of Biological... Feb 2024Chronic constipation has been associated with depression-like behavior. Previous study identified the crucial role of gut microbiota in the development of constipation...
Chronic constipation has been associated with depression-like behavior. Previous study identified the crucial role of gut microbiota in the development of constipation and depression. Dietary inulin (INU) could regulate gut microbiota. Whether INU treatment could ameliorate constipation induced depression was not clear. For this purpose, male CD-1 mice were administered diphenoxylate (20 mg/kg body weight/day) to induce constipation. We found that INU (10 % in standard diet) alleviated the diphenoxylate-induced constipation, manifested as the increase weight and moisture content of feces. Furthermore, the associated depression and anxiety-like behavior disorders were improved by inhibiting neuro-inflammation and preventing synaptic ultrastructure damage under INU treatment. Moreover, INU pretreatment improved the diphenoxylate-induced gut barrier damage by upregulating tight junction protein expression. INU also reshaped gut microbiota in constipation mice by increasing the relative abundance of Bacteroides and Proteobacteria and downregulating the abundance of Muribacalum and Melaminabacteria. The effects of INU on diphenoxylate-induced depression were abolished by gut microbiota depletion via antibiotic treatment. In addition, INU increased the concentration of short chain fatty acids (SCFAs) in feces contents. Meanwhile, supplementation of SCFAs could also partly improve diphenoxylate-induced depression. In conclusion, INU intake was a potential nutritional intervention strategy to prevent constipation induced depression via microbiota-gut-SCFAs axis.
Topics: Male; Mice; Animals; Inulin; Gastrointestinal Microbiome; Depression; Diphenoxylate; Fatty Acids, Volatile; Constipation; Diet; Anxiety
PubMed: 38219945
DOI: 10.1016/j.ijbiomac.2024.129420 -
Medeniyet Medical Journal Dec 2023Potentially inappropriate medications (PIM) is a crucial problem in the geriatric population. The amount of prescription and unadherence increase because of the...
OBJECTIVE
Potentially inappropriate medications (PIM) is a crucial problem in the geriatric population. The amount of prescription and unadherence increase because of the different problems encountered in cancer patients. Our aim was to evaluate the effects of PIM in patients with gastrointestinal system cancer and to investigate its relationship with chemotherapy side effects, mortality, and progression.
METHODS
This retrospective cohort study assessed 154 patients with gastrointestinal system cancer. Demographics and disease features, the presence of PIM according to the "TIME-to-STOP" criteria and baseline laboratory parameters were recorded. The effects of PIM on survival and adverse treatment events were evaluated.
RESULTS
66.9% of the cases were male and 33.1% were female. The mean age was 71.9±6.4 years. The most common side effects of chemotherapy are nausea, vomiting, kidney injury, and pain. The most frequently used prescriptions among the 98 PIMs were gliclazide, hyoscine N-butylbromide, simethicone, diphenoxylate atropine, and thiocolchicoside. PIM was detected in 68.1% of the participants. Chemotherapy side effects were more common in PIM group (p<0.001, odds ratio =5.6). PIM had no effect on mortality. Factors associated with mortality were age, stage, albumin, creatinine, operation history, and progression. A significant relationship was found between age, cancer stage, albumin, creatinine, operation history, and PIM in the regression model. There was no relationship between PIM and progression-free survival.
CONCLUSION
Chemotherapy toxicity may increase with PIM detected on diagnosis. We suggest that PIM is an important factor in predicting the side effects of chemotherapy and minimizing the adverse effects.
PubMed: 38148726
DOI: 10.4274/MMJ.galenos.2023.03063 -
Experimental Biology and Medicine... Dec 2023In clinical trials, rhubarb extract (Rb) was demonstrated to efficiently alleviate constipation. We would like to find out the underlying mechanism of rhubarb relieving...
In clinical trials, rhubarb extract (Rb) was demonstrated to efficiently alleviate constipation. We would like to find out the underlying mechanism of rhubarb relieving constipation. However, there are few studies on the effects of rhubarb on colonic mucus secretion and constipation. The aim of this study was to investigate the effects of rhubarb on colonic mucus secretion and its underlying mechanism. The mice were randomly divided into four groups. Group I was the control group and Group II was the rhubarb control group, with Rb (24 g/kg body weight [b.w.]) administered through intragastric administration for three days. Group III mice were given diphenoxylate (20 mg/kg b.w.) for five days via gavage to induce constipation. Group IV received diphenoxylate lasting five days before undergoing Rb administration for three days. The condition of the colon was evaluated using an endoscope. Particularly, the diameter of blood vessels in the colonic mucosa expanded considerably in constipation mice along with diminishing mucus output, which was in line with the observation via scanning electron microscope (SEM) and transmission electron microscope (TEM). We also performed metagenomic analysis to reveal the microbiome related to mucin gene expression level referring to mucin secretion. In conclusion, Rb relieves constipation by rebuilding mucus homeostasis and regulating the microbiome.
Topics: Mice; Animals; Rheum; Diphenoxylate; Mucins; Constipation; Colon; Mucus; Homeostasis
PubMed: 38073524
DOI: 10.1177/15353702231211859