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Asian Journal of Psychiatry Feb 2020
Review
Topics: Adult; Cholinergic Antagonists; Dicyclomine; Humans; Male; Substance-Related Disorders
PubMed: 31864128
DOI: 10.1016/j.ajp.2019.101891 -
Research in Pharmaceutical Sciences Oct 2019Galantamine (GAL) is a drug for treating Alzheimer's disease which has reasonable and no significant side effects. Studies have shown that GAL possesses antioxidant,...
Galantamine (GAL) is a drug for treating Alzheimer's disease which has reasonable and no significant side effects. Studies have shown that GAL possesses antioxidant, anti-inflammatory, and cholinomimetic effects that might be beneficial for inflammatory bowel disease. Therefore, this study was aimed to investigate the anti-inflammatory effect of GAL on acetic acid-induced colitis in rats. GAL at 0.25, 1.25, 2.5 mg/kg/day was administrated orally (p.o.) to different groups of male Wistar rats 2 h before induction of ulcer with acetic acid 3% and continued for 5 consecutive days. Dicyclomine (DIC) was similarly used alone (5 mg/kg/day, p.o.) or together with GAL at doses already mentioned to delineate the impact of muscarinic pathway in probable beneficial effects of GAL on colitis. Control and reference groups received distilled water (5 mL/kg, p.o.), prednisolone (4 mg/kg/day, p.o.), or mesalazine (100 mg/kg/day, p.o.) respectively. At day 6, tissue injuries were assessed for macroscopic, histopathologic, and biochemical indices of myeloperoxidase and MPO activity. Results showed that GAL at 3 applied doses, alone or in combination with DIC diminished ulcer index, total colitis index, and MPO activity as important biomarkers of colitis. DIC alone was not effective on most parameters and its concurrent administration with GAL couldn't reverse its antiulcerative effects. Prednisolone and mesalazine were both effective in this relation. The current research indicated that GAL had anti-inflammatory and antiulcerative activities independent of its muscarinic effects. Thus the antioxidant and anti-inflammatory effects may account for its anti-inflammatory and anti-ulcerative properties. Nevertheless, further detailed studies are warranted for exact elucidation of GAL mechanism on inflammation and colitis.
PubMed: 31798655
DOI: 10.4103/1735-5362.268199 -
Scientific Reports Sep 2019Memory loss is one of the most tragic symptoms of Alzheimer's disease. Our laboratory has recently demonstrated that 'i-Extract' of Ashwagandha (Withania somnifera)...
Memory loss is one of the most tragic symptoms of Alzheimer's disease. Our laboratory has recently demonstrated that 'i-Extract' of Ashwagandha (Withania somnifera) restores memory loss in scopolamine (SC)-induced mice. The prime target of i-Extract is obscure. We hypothesize that i-Extract may primarily target muscarinic subtype acetylcholine receptors that regulate memory processes. The present study elucidates key target(s) of i-Extract via cellular, biochemical, and molecular techniques in a relevant amnesia mouse model and primary hippocampal neuronal cultures. Wild type Swiss albino mice were fed i-Extract, and hippocampal cells from naïve mice were treated with i-Extract, followed by muscarinic antagonist (dicyclomine) and agonist (pilocarpine) treatments. We measured dendritic formation and growth by immunocytochemistry, kallikrein 8 (KLK8) mRNA by reverse transcription polymerase chain reaction (RT-PCR), and levels of KLK8 and microtubule-associated protein 2, c isoform (MAP2c) proteins by western blotting. We performed muscarinic receptor radioligand binding. i-Extract stimulated an increase in dendrite growth markers, KLK8 and MAP2. Scopolamine-mediated reduction was significantly reversed by i-Extract in mouse cerebral cortex and hippocampus. Our study identified muscarinic receptor as a key target of i-Extract, providing mechanistic evidence for its clinical application in neurodegenerative cognitive disorders.
Topics: Animals; Blotting, Western; Dendrites; Dicyclomine; Female; Male; Memory; Mice; Mice, Transgenic; Nerve Regeneration; Neuroprotective Agents; Pilocarpine; Plant Extracts; Receptor, Muscarinic M1; Reverse Transcriptase Polymerase Chain Reaction; Scopolamine; Withania
PubMed: 31570736
DOI: 10.1038/s41598-019-48238-6 -
Nature Reviews. Disease Primers Sep 2019Nausea and vomiting of pregnancy (NVP) is a common condition that affects as many as 70% of pregnant women. Although no consensus definition is available for hyperemesis... (Review)
Review
Nausea and vomiting of pregnancy (NVP) is a common condition that affects as many as 70% of pregnant women. Although no consensus definition is available for hyperemesis gravidarum (HG), it is typically viewed as the severe form of NVP and has been reported to occur in 0.3-10.8% of pregnant women. HG can be associated with poor maternal, fetal and child outcomes. The majority of women with NVP can be managed with dietary and lifestyle changes, but more than one-third of patients experience clinically relevant symptoms that may require fluid and vitamin supplementation and/or antiemetic therapy such as, for example, combined doxylamine/pyridoxine, which is not teratogenic and may be effective in treating NVP. Ondansetron is commonly used to treat HG, but studies are urgently needed to determine whether it is safer and more effective than using first-line antiemetics. Thiamine (vitamin B1) should be introduced following protocols to prevent refeeding syndrome and Wernicke encephalopathy. Recent advances in the genetic study of NVP and HG suggest a placental component to the aetiology by implicating common variants in genes encoding placental proteins (namely GDF15 and IGFBP7) and hormone receptors (namely GFRAL and PGR). New studies on aetiology, diagnosis, management and treatment are under way. In the next decade, progress in these areas may improve maternal quality of life and limit the adverse outcomes associated with HG.
Topics: Antiemetics; Dicyclomine; Doxylamine; Drug Combinations; Female; Growth Differentiation Factor 15; Humans; Hyperemesis Gravidarum; Mass Screening; Nausea; Pregnancy; Pyridoxine
PubMed: 31515515
DOI: 10.1038/s41572-019-0110-3 -
Asian Journal of Psychiatry Aug 2019Prescription drug suicide merits study to guide the development of strategies to reduce suicide risk. We examined prescription drug suicide specifically in non-abusers...
BACKGROUND
Prescription drug suicide merits study to guide the development of strategies to reduce suicide risk. We examined prescription drug suicide specifically in non-abusers of prescription drugs; this is a relatively unexplored subject.
METHODS
Six-year data on prescription drug suicide in non-abusers were extracted from the records of the Department of Forensic Medicine at the All India Institute of Medical Sciences, New Delhi. These records contained information obtained from the scene of the suicide, from interviews with relatives of the deceased, and from forensic toxicological analyses at two laboratories.
RESULTS
There were 27 (8%) cases of prescription drug suicide in non-abusers out of 338 cases of suicidal poisoning. The mean age of this sample was 26 years. The sample was 74% male. Nearly half of the cases (44%) were students. A combination of dextropropoxyphene with dicyclomine, with or without paracetamol, was used by 41% of cases. Overdose was achieved through the ingestion of 10-40 (median, 30) tablets or by the injection of 2-3 (median, 2) vials of medication. In 52% of cases, it appeared that the drugs had been procured over the counter.
CONCLUSIONS
It is reassuring that the absolute number of prescription drug suicides in non-abusers was small; the findings, however, are important because they could serve as a baseline for assessing time trends in future studies. For the present, we suggest that prescription drugs of potential abuse, especially those containing opioids and antispasmodics, should be prescribed and dispensed judiciously, especially to youth.
Topics: Adult; Analgesics, Opioid; Drug Overdose; Female; Forensic Medicine; Humans; India; Male; Parasympatholytics; Physicians; Prescription Drugs; Retrospective Studies; Students; Suicide; Universities; Young Adult
PubMed: 31374376
DOI: 10.1016/j.ajp.2019.07.039 -
Journal of Clinical Epidemiology Dec 2019The aim of the study was to quantify the risk of major congenital malformations (MCM) associated with first-trimester exposure to antiemetics.
OBJECTIVES
The aim of the study was to quantify the risk of major congenital malformations (MCM) associated with first-trimester exposure to antiemetics.
STUDY DESIGN AND SETTING
Using the Quebec Pregnancy Cohort (1998-2015), first-trimester doxylamine-pyridoxine, metoclopramide, and ondansetron exposures were assessed for their association with MCM. Generalized estimating equations were used to estimate odds ratios (OR), adjusting for potential confounders (aOR).
RESULTS
Within 17 years of follow-up, the prevalence of antiemetic use during pregnancy increased by 76%. Within our cohort, 45,623 pregnancies were exposed to doxylamine-pyridoxine, 958 to metoclopramide, and 31 to ondansetron. Doxylamine-pyridoxine and metoclopramide use were associated with an increased risk of overall MCM (aOR 1.07, 95% confidence interval [CI]: 1.03-1.11; 3,945 exposed cases) and (aOR 1.27, 95% CI: 1.03-1.57; 105 exposed cases), respectively. Doxylamine-pyridoxine exposure was associated with increased risks of spina bifida (aOR 1.87, 95% CI: 1.11-3.14; 23 exposed cases), nervous system (aOR 1.25, 95% CI: 1.06-1.47; 225 exposed cases), and musculoskeletal system defects (aOR 1.08, 95% CI: 1.02-1.14; 1,735 exposed cases). Metoclopramide exposure was associated with an increased risk of genital organ defects (aOR 2.26, 95% CI: 1.14-4.48; 10 exposed cases). No statistically significant association was found between ondansetron exposure and the risk of overall MCM.
CONCLUSION
First-trimester doxylamine-pyridoxine and metoclopramide exposure was associated with a significantly increased risk of overall and specific MCM.
Topics: Abnormalities, Drug-Induced; Adult; Antiemetics; Cohort Studies; Dicyclomine; Doxylamine; Drug Combinations; Female; Humans; Male; Maternal Age; Metoclopramide; Nausea; Ondansetron; Pregnancy; Pregnancy Trimester, First; Prevalence; Pyridoxine; Quebec; Vomiting; Young Adult
PubMed: 31352006
DOI: 10.1016/j.jclinepi.2019.07.014 -
Drug and Therapeutics Bulletin Mar 2019
Review
Topics: Antiemetics; Dicyclomine; Doxylamine; Drug Combinations; Female; Humans; Nausea; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications; Pyridoxine; Vomiting
PubMed: 30705026
DOI: 10.1136/dtb.2018.000053 -
Food & Function Jan 2019Theanine (γ-glutamylethylamide), an amino acid in tea, is a putative neuroprotective and antioxidant compound capable of improving lifespan and cognitive function....
Theanine (γ-glutamylethylamide), an amino acid in tea, is a putative neuroprotective and antioxidant compound capable of improving lifespan and cognitive function. Because we previously reported cognitive dysfunction in klotho mutant mice via down-regulation of janus kinase 2 (JAK2) and signal transducer and activator of transcription3 (STAT3), M1 muscarinic cholinergic receptor (M1 mAChR), and ERK signaling, we, therefore, investigated whether self-administration of theanine affects memory dysfunction in response to klotho gene depletion in mice, and whether theanine modulates the JAK2/STAT3, M1 mAChR, and ERK signaling network. Theanine significantly attenuated memory impairments in klotho mutant mice. Moreover, theanine self-administration significantly attenuated inhibitions of JAK2/STAT3 phosphorylation, M1 mAChR expression, and ERK1/2 phosphorylation in the hippocampus of klotho mutant mice. Consistently, AG490, a JAK2/STAT3 inhibitor, dicyclomine, an M1 mAChR antagonist, or U0126, an ERK1/2 inhibitor, significantly counteracted theanine-induced attenuation of memory impairment induced by klotho gene depletion in mice. Our study suggests that theanine attenuates memory impairments in a genetic aging model via up-regulation of JAK2/STAT3, M1 mAChR, and ERK signaling.
Topics: Animals; Female; Glucuronidase; Glutamates; Hippocampus; Humans; Janus Kinase 2; Klotho Proteins; Male; Memory; Memory Disorders; Mice; Mice, Knockout; STAT3 Transcription Factor
PubMed: 30574980
DOI: 10.1039/c8fo01577e -
The Turkish Journal of Gastroenterology... Mar 2019
Topics: Acute Disease; Dicyclomine; Female; Humans; Middle Aged; Pancreatitis
PubMed: 30459133
DOI: 10.5152/tjg.2018.18411 -
Molecules (Basel, Switzerland) Oct 2018The Emerald Ash Borer (EAB), , Fairmaire, an Asian invasive alien buprestid has devastated tens of millions of ash trees ( spp.) in North America. Foliar phytochemicals...
The Emerald Ash Borer (EAB), , Fairmaire, an Asian invasive alien buprestid has devastated tens of millions of ash trees ( spp.) in North America. Foliar phytochemicals of the genus (Oleaceae): (Green ash), (White ash), (Bush) Bush. (Pumpkin ash), Michx. (Blue ash), Marsh. (Black ash) and . (Manchurian ash) were investigated using HPLC-MS/MS and untargeted metabolomics. HPLC-MS/MS help identified 26 compounds, including phenolics, flavonoids and coumarins in varying amounts. Hydroxycoumarins, esculetin, esculin, fraxetin, fraxin, fraxidin and scopoletin were isolated from blue, black and Manchurian ashes. High-throughput metabolomics revealed 35 metabolites, including terpenes, secoiridoids and lignans. Metabolomic profiling indicated several upregulated putative compounds from Manchurian ash, especially fraxinol, ligstroside, oleuropin, matairesinol, pinoresinol glucoside, 8-hydroxypinoresinol-4-glucoside, verbenalin, hydroxytyrosol-1--glucoside, totarol and ar-artemisene. Further, dicyclomine, aphidicolin, parthenolide, famciclovir, ar-turmerone and myriocin were identified upregulated in blue ash. Principal component analysis demonstrated a clear separation between Manchurian and blue ashes from black, green, white and pumpkin ashes. The presence of defensive compounds upregulated in Manchurian ash, suggests their potential role in providing constitutive resistance to EAB, and reflects its co-evolutionary history with , where they appear to coexist in their native habitats.
Topics: Animals; Chromatography, High Pressure Liquid; Coleoptera; Coumarins; Flavonoids; Fraxinus; Metabolome; Metabolomics; Molecular Structure; Phenols; Tandem Mass Spectrometry
PubMed: 30360500
DOI: 10.3390/molecules23112734