Study Of Alvimopan Drug For Treatment Of Constipation Due To Prescription Pain Medication
Ontology highlight
ABSTRACT:
DISEASE(S): Gastrointestinal Diseases,Intestinal Diseases,Constipation,Bowel Dysfunction
PROVIDER: 2012159 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
Project description:Neuropathic pain (NP) is a complex chronic pain due to the nervous system damage or diseases.Yuan-Hu Zhi Tong Prescription (YZP) is a well-known Traditional Chinese Medicine (TCM) formula for pain relief, which is composed of Corydalis Rhizoma (Yuanhu, YH) and Angelicae Dahuricae Radix (Baizhi, BZ). However, understanding of the analgesic and compatibility mechanisms of YZP remains limited. The present study found that YZP was more effective in relieving mechanical allodynia and thermal hypersensitivity than YH and BZ administered alone. To understand the potential analgesic and compatibility mechanisms of YZP on neuropathic pain (NP), RNA-seq and bioinformatics analyses were performed. The results revealed that YZP exerts analgesic effects mainly by relieving inflammation in the spinal cord through various mechanisms, such as suppressing leukocyte activation and cytokine-mediated signaling pathways. Moreover, YZP can relieve NP by modulating the neuropeptide signaling pathway and promoting damaged tissue regeneration. In terms of compatibility, YH and BZ demonstrated synergistic effects on the inflammatory response and neuropeptide signaling pathway. Furthermore, BZ was found to regulate calcium ion transport and promote skeletal muscle tissue regeneration, thereby alleviating concomitant symptoms of NP. Hub genes such as Ucn, Ptgs2, Gal, and others may play a pivotal role in YZP analgesia and the synergistic effects of YH-BZ compatibility.
2024-11-11 | GSE245768 | GEO
Project description:Abstract Background Chronic constipation is prevalent and involves both colon sensitivity and various changes in intestinal bacteria, particularly mucosa-associated microflora. Here we examined regulatory mechanisms of TRPV4 expression by co-culturing colon epithelial cell lines with intestinal bacteria and their derivatives. We also investigated TRPV4 expression in colon epithelium from patients with constipation. Methods Colon epithelial cell lines were co-cultured with various enterobacteria (bacterial components and supernatant), folate, LPS, or short chain fatty acids (SCFAs). TRPV4 expression levels and promoter DNA methylation were assessed using pyrosequencing, and microarray network analysis. For human samples, correlation coefficients were calculated and multiple regression analyses were used to examine the association between clinical background, rectal TRPV4 expression level and mucosa-associated microbiota. Results Co-culture of CCD841 cells with P. acnes, C. perfringens, or S. aureus transiently decreased TRPV4 expression but did not induce methylation. Co-culture with clinical isolates and standard strains of K. oxytoca, E. faecalis, or E. coli increased TRPV4 expression in CCD841 cells, and TRPV4 and TNF-alpha expression were increased by E. coli culture supernatants but not bacterial components. Although folate, LPS, IL-6, TNF-alpha, or SCFAs alone did not alter TRPV4 expression, TRPV4 expression following exposure to E. coli culture supernatants was inhibited by butyric acid or TNF-alphaR1 inhibitor and increased by p38 inhibitor. Microarray network analysis showed activation of TNF-alpha, cytokines, and NOD signaling. TRPV4 expression was higher in constipated patients from the terminal ileum to the colorectum, and multiple regression analyses showed that low stool frequency, frequency of defecation aids, and duration were associated with TRPV4 expression. Meanwhile, incomplete defecation, time required to defecate, and number of defecation failures per 24 hours were associated with increased E. faecalis frequency. Conclusions Colon epithelium cells had increased TRPV4 expression upon co-culture with K. oxytoca, E. faecalis, or E. coli supernatants, as well as TNFα-stimulated TNFαR1 expression via a pathway other than p38. Butyrate treatment suppressed this increase. Epithelial TRPV4 expression was increased in constipated patients, suggesting that TRPV4 together with increased frequency of E. faecalis may be involved in the pathogenesis of various constipation symptoms.
2022-07-15 | GSE208164 | GEO
Project description:To pinpoint a distinctive gene associated with constipation resulting from C3 deficiency, we conducted microarray hybridization using total RNA extracted from the mid colon of C3 knockout (C3 KO) mice. Identification of causal genes through comparison of gene expression levels in mice induced with C3 deficiency.
2024-04-17 | GSE261184 | GEO
Project description:In order to characterize the changes in global gene expression in the distal colon of constipated SD rats in response to the laxative effects induced by aqueous extract of Liriope platyphylla (AEtLP) including isoflavone, saponin, oligosaccharide, succinic acid and hydroxyproline, total RNA extracted from the distal colon of AEtLP-treated constipation rats was hybridized to oligonucleotide microarrays.Overall, 581 genes were up-regulated and 216 genes were down-regulated by constipation induced by loperamide, while 67 genes were up-regulated and 421 genes were down-regulated by AEtLP treatment in constipated rats compared to controls. Among the transcripts up-regulated by constipation, 89 were significantly down-regulated and 20 were recovered to normal levels by AEtLP treatment. The major genes in the down-regulated categories included Slc9a5, klk10, Fgf15 and Alpi, while the major genes in the recovered categories were Cyp2b2, Ace, G6pc and Setbp1. However, nine of these genes that were down-regulated by constipation were significantly up-regulated and four were recovered to normal levels by AEtLP treatment. The major genes in the up-regulated categories included Serpina3n, Lcn2 and Slc5a81, while the major genes in the recovered categories were Tmem45a, Rerg and Rgc32. Constipation was induced in SD rats by subcutaneous injection of loperamide for 3 days. At 15 hr after the final treatment of loperamide, each animal were received a consistent volume of water or 15 uL/g body weight of AEtLP (1,000 mg/kg weight) via oral administration for once at 9 AM.
2014-10-04 | E-GEOD-62041 | biostudies-arrayexpress
Project description:This study is intended to investigate the recommended dose of alvimopan in doses 0.25mg/day (0.25mg, OD), 0.5mg/day (0.25mg, BID) or 1mg/day (0.5mg, BID) or placebo for 3 weeks in patients who receive opioids for the management of cancer pain and develop constipation, by giving overall consideration to the efficacy and safety data in each treatment group. Also, efficacy and safety data of alvimopan in the recommended dose group will be compared with those of placebo and to confirm alvimopan’s safety and efficacy.
| 2029315 | ecrin-mdr-crc
Project description:In order to characterize the changes in global gene expression in the distal colon of constipated SD rats in response to the laxative effects induced by aqueous extract of Liriope platyphylla (AEtLP) including isoflavone, saponin, oligosaccharide, succinic acid and hydroxyproline, total RNA extracted from the distal colon of AEtLP-treated constipation rats was hybridized to oligonucleotide microarrays.Overall, 581 genes were up-regulated and 216 genes were down-regulated by constipation induced by loperamide, while 67 genes were up-regulated and 421 genes were down-regulated by AEtLP treatment in constipated rats compared to controls. Among the transcripts up-regulated by constipation, 89 were significantly down-regulated and 20 were recovered to normal levels by AEtLP treatment. The major genes in the down-regulated categories included Slc9a5, klk10, Fgf15 and Alpi, while the major genes in the recovered categories were Cyp2b2, Ace, G6pc and Setbp1. However, nine of these genes that were down-regulated by constipation were significantly up-regulated and four were recovered to normal levels by AEtLP treatment. The major genes in the up-regulated categories included Serpina3n, Lcn2 and Slc5a81, while the major genes in the recovered categories were Tmem45a, Rerg and Rgc32.
2014-10-04 | GSE62041 | GEO
Project description:Study SB-767905/008 was a multicenter study to evaluate the effectiveness and safety of multiple dosage regimens of an investigational drug for the treatment of constipation due to prescription pain medication in participants with cancer pain.
Study ABD101684 will serve as an extension to Study SB-767905/008 and offer continued access to blinded investigational product to participants who have completed the original study. The purpose of Study ABD101684 is to evaluate the safety and efficacy of alvimopan compared to placebo in subjects who completed Study SB-767905/008 and elected to participate in this extension study.
| 2014660 | ecrin-mdr-crc
Project description:Adults who are taking opioid therapy for persistent non-cancer pain and have resulting opioid-induced bowel dysfunction (OBD) will be randomized (1:1:1) to one of 2 alvimopan arms, or to placebo. The primary objective of this phase 3 confirmatory study is to compare alvimopan with placebo for efficacy in the treatment of OBD. The primary efficacy endpoint is based on frequency of bowel movements. Subjects will be required to: (1) track their bowel movements and other bowel symptoms and (2) attend 6 clinic visits over 4 months.
| 2023988 | ecrin-mdr-crc
Project description:BACKGROUND: One of the most important risk factors for stroke is hypertension. A number of studies have attempted to identify the most effective anti-hypertensive therapeutic group for stroke prevention. Using an epidemiologic approach we aimed to find correlations based on Hungarian data on stroke-mortality and on prescription routine of anti-hypertensive therapeutics in three different counties, showing significant difference in stroke mortality. METHODS: We have used the official yearly reports on stroke-mortality for the period 2003-2008. Based on the significant differences in the change in mortality due to stroke three counties were selected: Baranya, Bekes and Hajdu-Bihar. The usage of antihypertensive therapeutic groups was analyzed. The correlation of stroke mortality difference and different antihypertensive treatment habits was analyzed by using normality test, time series analyses, correlation coefficient, paired samples test, one sample test and chi-square test. RESULTS: For the year 2003 stroke-mortality standardized with the county population number was highest in county Bekes, followed by county Baranya and county Hajdu-Bihar. For each year stroke mortality has shown significant (p < 0.0001) difference between the three counties and the ranking/order of the counties has been preserved over time. During the period of our study, an increase in the number of days of treatment was observed for most of the anti-hypertensive drugs listed. We have observed that the increased use of high-ceiling diuretics resulted in a mortality advantage, and the reduction in use of calcium channel blockers with direct cardiac effect had negative consequences. CONCLUSIONS: The authors acknowledge that by limiting the study to three counties the findings cannot be generalized to the whole Hungarian population. Two trends can still be identified:i) increased number of days of treatment (and therefore the probable use) of high-ceiling diuretics is associated with reduction in mortality due to stroke and its immediate complications; ii) reduction in the use of non-dihidropiridin CCBs does not seem justified, as their use appears to be advantageous in stroke prevention. Authors put emphasis on the importance of the adherence of the patients to the preventive therapies. Health care professionals could provide an important added value to the life long preventive therapies by improving the compliance of their patients, giving personalized care and advice.
| S-EPMC3323458 | biostudies-literature