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Alimentary Pharmacology & Therapeutics Jan 2010Despite setbacks to the approval of new medications for the treatment of irritable bowel syndrome, interim guidelines on endpoints for irritable bowel syndrome (IBS)... (Review)
Review
BACKGROUND
Despite setbacks to the approval of new medications for the treatment of irritable bowel syndrome, interim guidelines on endpoints for irritable bowel syndrome (IBS) trials have enhanced interest as new targets for medical therapy are proposed based on novel mechanisms or chemical entities.
AIMS
To review the approved lubiprostone, two targets that are not meeting expectations (tachykinins and corticotrophin-releasing hormone), the efficacy and safety of new 5-HT(4) agonists, intestinal secretagogues (chloride channel activators, and guanylate cyclase-C agonists), bile acid modulation, anti-inflammatory agents and visceral analgesics.
METHODS
Review of selected articles based on PubMed search and clinically relevant information on mechanism of action, safety, pharmacodynamics and efficacy.
RESULTS
The spectrum of peripheral targets of medical therapy addresses chiefly the bowel dysfunction of IBS and these effects are associated with pain relief. The pivotal mechanisms responsible for the abdominal pain or visceral sensation in IBS are unknown. The new 5-HT(4) agonists are more specific than older agents and show cardiovascular safety to date. Secretory agents have high specificity, low bioavailability and high efficacy. The potential risks of agents 'borrowed' from other indications (such as hyperlipidaemia, inflammatory bowel disease or somatic pain) deserve further study.
CONCLUSIONS
There is reason for optimism in medical treatment of IBS with a spectrum of agents to treat bowel dysfunction. However, visceral analgesic treatments are still suboptimal.
Topics: Alprostadil; Bile; Gastrointestinal Motility; Humans; Irritable Bowel Syndrome; Lubiprostone; Quality of Life; Receptors, Serotonin, 5-HT3; Serotonin Receptor Agonists; Treatment Outcome
PubMed: 19785622
DOI: 10.1111/j.1365-2036.2009.04153.x -
Internal Medicine (Tokyo, Japan) 2021Digital clubbing has been regarded as an important sign in medicine. A 33-year-old woman with no history of hepatic, pulmonary, or malignant disease was referred to our...
Digital clubbing has been regarded as an important sign in medicine. A 33-year-old woman with no history of hepatic, pulmonary, or malignant disease was referred to our hospital. She had been taking lubiprostone every day for three years for constipation. Clubbing in her upper and lower limb digits began gradually about two years ago. The results of laboratory investigations were almost normal. We suspected the clubbed digits were a side effect of lubiprostone and confirmed that the levels of urinary prostaglandin E2 (PGE2), which can cause clubbed digits, were elevated. Thus, we instructed the woman to stop taking lubiprostone and monitored this lab value. However, the value continued to rise over 2 months to 41.9 μg/g Cr. During that time, she had been taking sennoside A B calcium instead of lubiprostone for constipation. Since sennoside A B calcium also has the effect of increasing PGE2, we ordered the discontinuation. Her urinary PGE2 to creatinine level normalized, and the clubbing improved after the discontinuation of these two medications.
Topics: Adult; Alprostadil; Constipation; Female; Humans; Liver; Lubiprostone; Neoplasms; Osteoarthropathy, Secondary Hypertrophic
PubMed: 34334594
DOI: 10.2169/internalmedicine.6104-20 -
Esophagus : Official Journal of the... Jul 2023To evaluate the long-term efficacy of transoral incisionless fundoplication (TIF) with Medigus Ultrasonic Surgical Endostapler (MUSE) for gastroesophageal reflux disease...
BACKGROUND
To evaluate the long-term efficacy of transoral incisionless fundoplication (TIF) with Medigus Ultrasonic Surgical Endostapler (MUSE) for gastroesophageal reflux disease (GERD).
METHODS
A total of 16 patients with proton pump inhibitor-dependent gastroesophageal reflux disease had undergone TIF by MUSE in Shanghai General Hospital (Shanghai, China)from March 2017 to December 2018. Patients were followed up at 6 months, and the GERD-health-related quality of life (GERD-HRQL) questionnaire score, the GERD questionnaire (GERD-Q) score, high-resolution esophageal manometry (HREM) and 24 h esophageal pH parameters, the Hill grade of the gastroesophageal flap valve (GEFV) and daily Proton pump inhibitor (PPI) consumption before and after procedure were compared. Patients also were followed up at 3 years and 5 years using a structured questionnaire via phone which evaluated symptoms of reflux, dose of PPI medication and side effects.
RESULTS
Follow-up data were collected from 13 patients, ranging from 38 to 63 months, 53 months on average. 10/13 patients reported symptomatic improvement and daily PPI consumption was stopped or halved in 11/13. After procedure, the mean scores of GERD-HRQL and GERD-Q were significantly increased. The mean DeMeester score, the mean acid exposure time percentage and the mean number of acid reflux episodes were significantly lower. The mean rest pressure at lower esophageal sphincter (LES) had no significant difference.
CONCLUSION
TIF by MUSE has significant efficacy in the treatment of PPI-dependent GERD, which can improve symptoms and life quality of patients, and reduce the acid exposure time for long-term. Chictr.org.cn.
TRIAL REGISTRATION
ChiCTR2000034350.
Topics: Humans; Fundoplication; Alprostadil; Quality of Life; Proton Pump Inhibitors; Ultrasonics; Treatment Outcome; China; Gastroesophageal Reflux
PubMed: 36877412
DOI: 10.1007/s10388-023-00992-3 -
Canadian Journal of Gastroenterology =... Oct 2011The present review has several objectives, the first of which is to review the pharmacology and selectivity of serotonergic agents to contrast the older serotonergic... (Review)
Review
The present review has several objectives, the first of which is to review the pharmacology and selectivity of serotonergic agents to contrast the older serotonergic agents (which were withdrawn because of cardiac or vascular adverse effects) with the newer generation serotonin receptor subtype 4 agonists. Second, the chloride ion secretagogues that act through the guanylate cyclase C receptor are appraised and their pharmacology is compared with the approved medication, lubiprostone. Third, the efficacy and safety of the application of bile acid modulation to treat constipation are addressed. The long-term studies of surgically induced excess bile acid delivery to the colon are reviewed to ascertain the safety of this therapeutic approach. Finally, the new drugs for opiate-induced constipation are introduced. Assuming these drugs are approved, practitioners will have a choice; however, patient responsiveness will be based on trial and error. Nevertheless, the spectrum of mechanisms and demonstrated efficacy and safety augur well for satisfactory treatment outcomes.
Topics: Alprostadil; Bile Acids and Salts; Chloride Channels; Chronic Disease; Constipation; Gastrointestinal Agents; Humans; Indoles; Lubiprostone; Organic Anion Transporters, Sodium-Dependent; Peptides; Receptors, Serotonin, 5-HT4; Serotonin 5-HT4 Receptor Agonists; Serotonin Agents; Symporters
PubMed: 22114755
DOI: No ID Found -
Scientific Reports Oct 2022Multilineage-differentiating stress-enduring (Muse) cells are non-tumorigenic pluripotent-like stem cells that exhibit triploblastic differentiation and...
Multilineage-differentiating stress-enduring (Muse) cells are non-tumorigenic pluripotent-like stem cells that exhibit triploblastic differentiation and self-renewability at the single-cell level, and are collectable as pluripotent surface marker SSEA-3(+) from the bone marrow (BM), peripheral blood, and organ connective tissues. SSEA-3(+) cells from human amniotic membrane mesenchymal stem cells (hAMSCs) were compared with hBM-Muse cells. Similar to hBM-Muse cells, hAMSC-SSEA-3(+) cells expressed pluripotency genes (OCT3/4, NANOG, and SOX2), differentiated into triploblastic cells from a single cell, self-renewed, and exhibited non-tumorigenicity. Notably, however, they exhibited unique characteristics not seen in hBM-Muse cells, including higher expression of genes related to germline- and extraembryonic cell-lineages compared with those in hBM-Muse cells in single-cell RNA-sequencing; and enhanced expression of markers relevant to germline- (PRDM14, TFAP2C, and NANOS3) and extraembryonic cell- (CDX2, GCM1, and ID2) lineages when induced by cytokine subsets, suggesting a broader differentiation potential similar to naïve pluripotent stem cells. t-SNE dimensionality reduction and Gene ontology analysis visualized hAMSC-SSEA-3(+) cells comprised a large undifferentiated subpopulation between epithelial- and mesenchymal-cell states and a small mesenchymal subpopulation expressing genes relevant to the placental formation. The AM is easily accessible by noninvasive approaches. These unique cells are a potentially interesting target naïve pluripotent stem cell-like resource without tumorigenicity.
Topics: Alprostadil; Amnion; Cell Differentiation; Cytokines; Female; Humans; Placenta; Pregnancy; RNA
PubMed: 36241699
DOI: 10.1038/s41598-022-22282-1 -
AAV-delivered muscone-induced transgene system for treating chronic diseases in mice via inhalation.Nature Communications Feb 2024Gene therapies provide treatment options for many diseases, but the safe and long-term control of therapeutic transgene expression remains a primary issue for clinical...
Gene therapies provide treatment options for many diseases, but the safe and long-term control of therapeutic transgene expression remains a primary issue for clinical applications. Here, we develop a muscone-induced transgene system packaged into adeno-associated virus (AAV) vectors (AAV) based on a G protein-coupled murine olfactory receptor (MOR215-1) and a synthetic cAMP-responsive promoter (P). Upon exposure to the trigger, muscone binds to MOR215-1 and activates the cAMP signaling pathway to initiate transgene expression. AAV enables remote, muscone dose- and exposure-time-dependent control of luciferase expression in the livers or lungs of mice for at least 20 weeks. Moreover, we apply this AAV to treat two chronic inflammatory diseases: nonalcoholic fatty liver disease (NAFLD) and allergic asthma, showing that inhalation of muscone-after only one injection of AAV-can achieve long-term controllable expression of therapeutic proteins (ΔhFGF21 or ΔmIL-4). Our odorant-molecule-controlled system can advance gene-based precision therapies for human diseases.
Topics: Mice; Humans; Animals; Alprostadil; Transgenes; Cycloparaffins; Odorants; Receptors, G-Protein-Coupled; Dependovirus; Genetic Vectors
PubMed: 38321056
DOI: 10.1038/s41467-024-45383-z -
The Journal of Investigative Dermatology Dec 2017With a rise in the prevalence of chronic wounds and other soft tissue defects, there is an urgent need to regenerate skin. Multilineage-differentiating stress-enduring...
With a rise in the prevalence of chronic wounds and other soft tissue defects, there is an urgent need to regenerate skin. Multilineage-differentiating stress-enduring cells were identified as distinct pluripotent stem cells in mesenchymal cell populations in humans. New research demonstrates the ability to effectively differentiate multilineage-differentiating stress-enduring cells into fibroblasts and keratinocytes for skin reconstitution.
Topics: Alprostadil; Cell Differentiation; Cell Lineage; Fibroblasts; Humans; Keratinocytes; Melanocytes; Mesenchymal Stem Cells; Regeneration; Regenerative Medicine
PubMed: 29169463
DOI: 10.1016/j.jid.2017.07.825 -
Neurology India 2009Vasoactive drug alprostadil improves microcirculation and can be effective in treating disorders of peripheral nerves. Vascular endothelial growth factor (VEGF) has been...
BACKGROUND
Vasoactive drug alprostadil improves microcirculation and can be effective in treating disorders of peripheral nerves. Vascular endothelial growth factor (VEGF) has been shown to have protective action in cerebral ischemia, disorders of spinal cord, and also peripheral nerves. However, the mechanism of action of VEGF in peripheral nerve injuries is uncertain.
OBJECTIVES
To study the effect of application of alprostadil on the pathological and functional repair of crush nerve injuries and also the expression of VEGF.
MATERIALS AND METHODS
Rat sciatic nerves were crushed by pincers to establish the model of crush injury. All of the 400 sprague dawley (SD) rats were randomly divided into: Control; saline; saline+VEGF-antibody; alprostadil; and alprostadil+VEGF antibody groups. The SPSS 11.5 software was used for statistical analysis. The expression of VEGF in dorsal root ganglia (DRGs), following crush injury to sciatic nerves, was studied by reverse transcribed-polymerase chain reaction (RT-PCR), immunohistochemistry, electromicroscope, and electrophysiology. The effects of alprostadil on expression of VEGF, repair of neural pathology, and recovery of neural function were also evaluated.
RESULTS
We found that VEGF messenger ribonucleic acid (mRNA) was significantly increased in alprostadil and alprostadil+VEGF-antibody groups, compared to the saline and saline+VEGF antibody groups. The number of VEGF-positive neurons was significantly increased in the alprostadil group, compared to the saline, saline+VEGF antibody, and alprostadil+VEGF antibody groups. Besides, addition of this drug also caused less pathological changes in DRGs, better improvement of nerve conduction velocities of sciatic nerves, and more increase of toe spaces of right hind limbs of rats.
CONCLUSIONS
The vasoactive agent alprostadil may reduce the pathological lesion of peripheral nerves and improve the rehabilitation of the neural function, which may relate to upregulation of the expression of VEGF, following crush injury to the peripheral nerves.
Topics: Alprostadil; Analysis of Variance; Animals; Antibodies; Disease Models, Animal; Female; Fibrinolytic Agents; Ganglia, Spinal; Gene Expression Regulation; Male; Microscopy, Immunoelectron; Nerve Regeneration; Neural Conduction; Psychomotor Performance; RNA, Messenger; Rats; Rats, Sprague-Dawley; Sciatic Neuropathy; Vascular Endothelial Growth Factor A
PubMed: 19770537
DOI: 10.4103/0028-3886.55583 -
Medical Science Monitor : International... Oct 2019BACKGROUND Alprostadil can inhibit inflammation and reduce inflammation-related injury in many inflammatory diseases. However, the anti-inflammatory effect of...
BACKGROUND Alprostadil can inhibit inflammation and reduce inflammation-related injury in many inflammatory diseases. However, the anti-inflammatory effect of alprostadil in decreasing acute pancreatitis (AP) injury remains unknow. This study aimed to investigate the possible protective effects and mechanism of alprostadil against AP in rats. MATERIAL AND METHODS Forty healthy Sprague‑Dawley rats were randomly divided into a control group, an AP group, an AP-alprostadil group, an AP-AG490 group, and an AP-(alprostadil+AG490) group. An animal model of acute pancreatitis was established. The pathological changes of the pancreases in each group were observed. We assessed levels of malondialdehyde (MDA), superoxide dismutase (SOD), and myeloperoxidase (MPO), as well as serum IL-1ß, IL-6, IL-10, and TNF-alpha. TUNEL assay was used to detect apoptosis of pancreatic cells. The proteins p-Jak2 and p-Stat3 were investigated by Western blot. RESULTS Compared with the control group, pancreatic pathological score, pancreatic apoptosis, MDA, MPO, serum IL-1ß, IL-6, and TNF-alpha levels were significantly higher in the AP group, and SOD levels were significantly decreased. Compared with the AP group, after treatment with alprostadil, AG490, and alprostadil+AG490, respectively, the pancreatic pathological score, apoptosis, MDA, MPO, serum IL-1ß, IL-6, and TNF-alpha were significantly decreased in AP rats, while SOD levels were significantly increased. The protein levels of p-JAK2 and p-STAT3 were significantly upregulated in the AP group compared with the control group, and the protein levels of p-JAK2 and p-STAT3 after treatment with alprostadil, AG490, and alprostadil+AG490 were significantly decreased, and the effect of alprostadil+AG490 was the strongest. CONCLUSIONS Alprostadil can reduce pancreatic tissue damage, delay pancreatic cell apoptosis, and reduce inflammation and anti-oxidative stress by inhibiting the JAK2/STAT3 signal pathway, thus protecting the pancreas.
Topics: Acinar Cells; Acute Disease; Alprostadil; Amylases; Animals; Apoptosis; Arginine; Cytokines; Inflammation Mediators; Janus Kinase 2; Lipopolysaccharides; Male; Oxidative Stress; Pancreas; Pancreatitis; Protective Agents; Rats, Sprague-Dawley; STAT3 Transcription Factor; Signal Transduction
PubMed: 31606729
DOI: 10.12659/MSM.919148 -
Yakugaku Zasshi : Journal of the... Jun 2004To study the effectiveness for the treatment of intermittent claudication (IC) of three drugs with antiplatelet effects, cilostazol, beraprost sodium, and prostaglandin... (Meta-Analysis)
Meta-Analysis Review
To study the effectiveness for the treatment of intermittent claudication (IC) of three drugs with antiplatelet effects, cilostazol, beraprost sodium, and prostaglandin E(1) (PGE(1)), by using a systemic review of literature and a meta-analysis. A search was undertaken for studies reported between 1966-2002 in the MEDLINE database, and references in published articles and reviews were obtained. Data for maximum walking distance (MWD), pain-free walking distance (PFWD), and adverse clinical events were extracted from the articles that met the inclusion criteria. The pooled estimates of the weighted mean differences (WMD) of MWD and PFWD for cilostazol were 52.19 m [95% confidence interval (CI) 32.08, 72.31] and 39.75 m [95% CI 23.39, 56.10], and those for PGE(1) were 100.27 m [95% CI 15.76, 184.78] and 55.73 [95% CI 21.54, 89.92], respectively. These differences were statistically significant between the test drugs and placebo. However there was no statistical significance difference between beraprost sodium and placebo, even though there was one study that showed a tendency for improvement in walking distance. The total rate of adverse clinical events in cilostazol and beraprost sodium was higher than that for placebo, while there was no statistical significant difference between PGE(1) and placebo, although PGE(1) had a higher tendency for adverse clinical events. The literature evaluation results and the meta-analysis suggest that these two drugs (cilostazol and PGE(1)) can be considered to be effective drugs for the treatment of IC. Due to current availability of only a few clinical reports, further studies are needed to clarify the efficacy of beraprost sodium in the treatment of IC.
Topics: Alprostadil; Cilostazol; Epoprostenol; Humans; Intermittent Claudication; Platelet Aggregation Inhibitors; Tetrazoles; Treatment Outcome; Walking
PubMed: 15170067
DOI: 10.1248/yakushi.124.321