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Bioengineered Dec 2021Recent findings have identified microbiota as crucial participants in many disease conditions, including cancers. Competing endogenous RNA (ceRNA) is regarded as a...
Recent findings have identified microbiota as crucial participants in many disease conditions, including cancers. Competing endogenous RNA (ceRNA) is regarded as a candidate mechanism involving relevant biological processes. We therefore constructed a ceRNA network using the TCGA and GEO database, to determine the potential mechanisms of microbiota-mediated colorectal carcinogenesis and progression. We found a total of 75 lncRNAs, 8 miRNAs, and 9 mRNAs in the probiotics-mediated ceRNA network and a total of 49 lncRNAs, 4 miRNAs, and 3 mRNA in the pathobiont-mediated ceRNA network, which could induce the microbiota-mediated carcinogenesis and progression. The GO and KEGG analysis indicated that the ceRNA network is mainly enriched in the metabolic process, and two unique pathways (the p53 signaling pathway and microRNA in cancer), respectively. A four-gene signature (FRMD6-AS2, DIRC3, LIFR-AS1, and MRPL23-AS1) was suggested as an independent prognostic factor. Four lncRNAs (LINC00355, KCNQ1OT1, LINC00491, and HOTAIR) were associated with poor survival. Three small molecule candidate anticancer drugs (Pentoxyverine, Rimexolone, and Doxylamine) were identified. A four-gene signature (FAM129A, BCL2, PMAIP1, and RPS6) is significantly correlated with immune infiltration level. This study provides a promising biomarker reservoir to explore the mechanism by which microbiota regulate the ceRNA network involving the immune response, and further participate in colorectal carcinogenesis and progression.
Topics: Antineoplastic Agents; Colorectal Neoplasms; Computational Biology; Gastrointestinal Microbiome; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Humans; Prognosis; Protein Interaction Maps; RNA, Messenger; RNA, Untranslated
PubMed: 34227920
DOI: 10.1080/21655979.2021.1940614 -
BMC Chemistry Mar 2023A sequential spectrophotometric resolution technique (SSRT) was developed in this study without the use of systematic separation procedures to determine drug of a...
The simultaneous measurement of quaternary mixture in over-the-counter cold medications using sequential spectrophotometric resolution approach enhanced with in-lab sample enrichment.
A sequential spectrophotometric resolution technique (SSRT) was developed in this study without the use of systematic separation procedures to determine drug of a quaternary combination; caffeine (CAF), pseudoephedrine (PSE), doxylamine succinate (DOX), and paracetamol (PAR). Their presence in a tablet with a gap ratio of 3:3:1:150, respectively, and their overlapping spectra with low absorptivities make their resolution and determination impossible without prior separation. successive ratio subtraction technique (SRST) and constant multiplication method were used to solve these problems. Furthermore, an in-lab sample enrichment technique was applied to increase minor components concentration and consequently their absorbanses (CAF, PSE, and DOX). The D absorption spectra were generated by successive ratios followed by subtraction and multiplication of the constants. The maximum absorbances of the drugs tested, namely (CAF, PSE, DOX and PAR) were measured at wavelengths of 272.0, 257.0, 260.0, and 248.0 nm, respectively. The limits of detection (LOD) and limits of quantification (LOQ) were 0.021, 0.124, 0.186, 0.137 and 0.070, 0.414, 0.621, 0.456 (µg/mL), respectively. The linearitiy ranges (µg/mL) were 1.0-22.0, 1.0-24.0, 10.0-90.0 and 1.0-15.0 for CAF, PSE, DOX, and PAR, respectively. The International Conference on Harmonization (ICH) guidelines were applied for method validation, and the results obtained were within the limited parameters. The finding results were compared to official and/or published analytical methods to determine the procedure's reliability. It was noted that there was no actual difference in accuracy and precision between both meyhods. The proposed technique is sensitive, selective and economic;so it can be applied to the simultaneous analysis of these drugs in their commercial tablets and/or in quality-control laboratories.
PubMed: 36949535
DOI: 10.1186/s13065-023-00931-4 -
JAMA Otolaryngology-- Head & Neck... Sep 2020Sinonasal remedies are the most frequently purchased category of over-the-counter (OTC) drugs in the United States. A variety of options for relief are available under...
IMPORTANCE
Sinonasal remedies are the most frequently purchased category of over-the-counter (OTC) drugs in the United States. A variety of options for relief are available under proprietary names, although the actual number of available options may not be readily appreciated by the consumer or the clinician.
OBJECTIVE
To determine the prevalence of specific ingredients in OTC sinonasal products.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional study took physical inventory of brand-name and generic OTC drugs marketed as sinus, cold, allergy, or nasal remedies. Retail pharmacies in New Orleans, Louisiana, commercial websites, and the Drugs, Herbs and Supplements section of MedlinePlus and drugs.com were searched. Data were collected and analyzed from July 1 to 31, 2018.
MAIN OUTCOMES AND MEASURES
Frequency of active ingredients in OTC formulations.
RESULTS
Five pharmacies were visited to identify 18 brands, for which the commercial websites were then searched. The 14 most common brands represented 211 unique products. Only 8 unique nonanalgesic ingredients were identified among these products, with many products sold under the same brand name and with the same active ingredient. Phenylephrine hydrochloride, dextromethorphan hydrobromide, pseudoephedrine hydrochloride, guaifenesin, chlorpheniramine maleate, brompheniramine maleate, diphenhydramine hydrochloride, and doxylamine succinate were the common active ingredients, with all available OTC sinonasal remedies consisting of 1 or more of these ingredients. The frequency of occurrence of each ingredient ranged from 10 to 261 different products. Combinations of 2, 3, or 4 active ingredients occurred frequently in OTC sinonasal products.
CONCLUSIONS AND RELEVANCE
These findings suggest that proliferation of brand extension products under a common name is pervasive. Clinicians should be aware of the large array of redundant OTC formulations and lack of specificity when discussing brand-name sinonasal remedies with their patients.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Cross-Sectional Studies; Drug Combinations; Histamine Antagonists; Humans; Nonprescription Drugs; Respiratory System Agents; United States
PubMed: 32672802
DOI: 10.1001/jamaoto.2020.1836 -
Spectrochimica Acta. Part A, Molecular... Feb 2021The combination of pyridoxine HCl (PYR) and doxylamine succinate (DOX) was proved to be effective and safe acting as the first line of pregnancy medication for vomiting...
In vitro analytical dissolution profiling of antiemetic delayed release tablets in two different dissolution media: Validated spectrophotometric methods versus reported HPLC.
The combination of pyridoxine HCl (PYR) and doxylamine succinate (DOX) was proved to be effective and safe acting as the first line of pregnancy medication for vomiting and nausea under a trade name; Vomibreak® delayed release tablets. This combination has been available in the Egyptian market since 2016. Dissolution study is a meaningful tool that represents a predictor of output because the rate controlling steps in any drug's absorption is the rate of discharging from its medicinal formulation. Generally, the dissolution test of all delayed release tablets is operated at two stages: first the acid stage then the buffer stage. In our work, the acid stage was performed in 0.1 N hydrochloric acid (0.1 M HCl) and the buffer one was in 0.2 M sodium phosphate buffer (0.2 M Na-PB), pH = 6.8, according to FDA guidelines. In present work, for the first time, this binary mixture was quantitatively determined by applying four spectrophotometric methods. PYR was directly determined by zero order spectra method (D) at 291.0 nm in the range 2.0-26.0 μg/mL in the acid stage and at 325.0 nm in the range 5.0-35.0 μg/mL in the buffer stage, where DOX show no interference in both cases. However, DOX was determined by three methods, namely, Dual wavelength (DW), Ratio difference (RD) and Derivative ratio (DD). DD was the chosen method for determination of DOX in the two-phase dissolution study of Vomibreak® tablets at 249.0 nm in the range 2.0-44.0 μg/mL and 273.0 nm in the range 5.0-100.0 μg/mL in acid and buffer phases, respectively. All of the suggested methods were tested in compliance with ICH guidelines, where all methods were found to be reliable, reproducible, and selective. A statistical comparison was computed between two analytical techniques of critical importance in the development of two media dissolution profile: proposed UV- spectrophotometric and reported HPLC methods where no significant difference was found. Difference (ƒ) and similarity (ƒ) factors were calculated for PYR and DOX and shown that ƒ was 1.490 and 1.654 and ƒ was 94.431 and 92.396 for PYR and DOX, respectively.
Topics: Antiemetics; Chromatography, High Pressure Liquid; Egypt; Female; Humans; Pregnancy; Solubility; Tablets
PubMed: 33049467
DOI: 10.1016/j.saa.2020.119013 -
Pharmacological Research Jan 2021Because observational studies often use imperfect measurements, results are prone to misclassification errors. We used as a motivating example the possible teratogenic... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Because observational studies often use imperfect measurements, results are prone to misclassification errors. We used as a motivating example the possible teratogenic risks of antiemetic agents in pregnancy since a large observational study recently showed that first-trimester exposure to doxylamine-pyridoxine was associated with significantly increased risk of congenital malformations as a whole, as well as central nervous system defects, and previous observational studies did not show such associations. A meta-analysis on this issue was carried out with the aim to illustrate how differential exposure and outcome misclassifications may lead to uncertain conclusions.
METHODS
Medline, searched to October 2019 for full text papers in English. Summary Odds Ratios (ORs) with confidence intervals (CIs) were calculated using random-effect models. Probabilistic sensitivity analyses were performed for evaluating the extension of differential misclassification required to account for the exposure-outcome association.
RESULTS
Summary ORs were 1.02 (95 % CI, 0.92-1.15), 0.99 (0.82-1.19) and 1.25 (1.08-1.44) for overall congenital, cardiocirculatory, and central nervous system malformations respectively. By assuming exposure and outcome bias factor respectively of 0.95 (i.e., newborns with congenital defects had exposure specificity 5% lower than healthy newborns) and 1.12 (i.e., exposed newborns had outcome sensitivity 12 % higher than unexposed newborns), summary OR of central nervous system defects became 1.13 (95 % CI, 0.99-1.29) and 1.17 (95 % CI, 0.99-1.38).
CONCLUSION
Observational investigations and meta-analyses of observational studies need cautious interpretations. Their susceptibility to several, often sneaky, sources of bias should be carefully evaluated.
Topics: Abnormalities, Drug-Induced; Antiemetics; Dicyclomine; Doxylamine; Drug Combinations; Female; Humans; Nausea; Observational Studies as Topic; Odds Ratio; Pregnancy; Pyridoxine; Scientific Experimental Error; Uncertainty; Vomiting
PubMed: 33031909
DOI: 10.1016/j.phrs.2020.105229 -
Gynecologie, Obstetrique, Fertilite &... Dec 2021Although there is no recommendation in France relating to the treatment of nausea and vomiting of pregnancy, there are some in other countries, where ondansetron, widely...
Although there is no recommendation in France relating to the treatment of nausea and vomiting of pregnancy, there are some in other countries, where ondansetron, widely used, appears to be an effective second-line treatment option behind doxylamine/vitamin B6 association and metoclopramide. However, based on some recent publication suggesting an increased risk of orofacial clefts and congenital heart defects in fetuses exposed in utero to ondansetron in the 1st trimester of pregnancy, the European Medicines Agency now states that this drug should not longer be used during this period. This 2019 decision is controversial and whether ondansetron can be used in pregnant women with severe vomiting during pregnancy is still in question.
Topics: Antiemetics; Cleft Lip; Cleft Palate; Female; Humans; Nausea; Ondansetron; Pregnancy; Vomiting
PubMed: 34700033
DOI: 10.1016/j.gofs.2021.10.009 -
Paediatric and Perinatal Epidemiology Jan 2021Although nausea and vomiting of pregnancy (NVP) is common, the secular and demographic trends of NVP and its treatments are not well-studied.
BACKGROUND
Although nausea and vomiting of pregnancy (NVP) is common, the secular and demographic trends of NVP and its treatments are not well-studied.
OBJECTIVES
To describe the prevalence and patterns of first-trimester NVP and selected treatments among controls in the National Birth Defects Prevention Study (NBDPS).
METHODS
National Birth Defects Prevention Study is a population-based case-control study of birth defects in the United States (1997-2011). We collected self-reported data about NVP and use of commonly reported pharmacological and herbal/natural treatments (ondansetron, promethazine, pyridoxine, metoclopramide, doxylamine succinate, ginger, phosphorated carbohydrate solution, and prochlorperazine) from mothers of non-malformed control infants. We estimated the prevalence of NVP and selected treatments and examined secular and demographic trends (education, race/ethnicity, and maternal age) for such use, adjusting for study centre.
RESULTS
Among 10 540 mothers of controls, 7393 women (70.1%) reported first-trimester NVP, and 12.2% of those used one or more of the commonly reported treatments. Specific treatment use varied after adjustment for study centre (ondansetron: 3.4%; promethazine: 4.2%; pyridoxine: 3.2%; metoclopramide: 0.7%; doxylamine succinate: 1.7%; ginger: 1.0%; phosphorated carbohydrate solution: 0.4%; and prochlorperazine: 0.3%). Treatment use increased for each agent over the study period. Women with more years of education reported more NVP and treatment use. White (72%), Hispanic (71%), and other race (73%) women reported more NVP than Black women (67%); White women used selected NVP treatments most frequently, and Black women used them more than Hispanic women. Though women aged 25-34 years reported more NVP (72%) than younger (69%) or older (67%) women, the frequency of medication use was similar among women aged 25-34 and ≥35, and lower among women aged <25 years.
CONCLUSIONS
National Birth Defects Prevention Study controls reported NVP at frequencies similar to those previously reported. Of note, we observed an increase in use of selected treatments over time, and variations in NVP and treatments by study site and demographic factors.
Topics: Antiemetics; Case-Control Studies; Female; Humans; Infant; Nausea; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Vomiting
PubMed: 32623767
DOI: 10.1111/ppe.12705 -
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 -
Biomedical Chromatography : BMC Nov 2019A novel generic reverse phase high performance liquid chromatography (RP-HPLC) method is developed and validated for simultaneous determination of seven pharmaceutically...
A novel generic reverse phase high performance liquid chromatography (RP-HPLC) method is developed and validated for simultaneous determination of seven pharmaceutically active ingredients, namely, acetaminophen, dextromethorphan, doxylamine, phenylephrine, guaifenesin, caffeine and aspirin. All seven ingredients were quantified in soft gel, syrup and tablet formulations of the over-the-counter US-marketed products, as per the guidelines of the International Conference on Harmonization. The separation was achieved in a 16 min run time on an Agilent Zorbax Phenyl column using a gradient method with two mobile phases. Mobile phase A was 0.15% trifluoro acetic acid in purified water and while mobile phase B was a mixture of acetonitrile and methanol (750:250 v/v) with 0.02% trifluoro acetic acid. The flow rate was 1.0 mL min and injection volume was 10 μL. Detection was performed at 280 nm using a photodiode array detector. As part of the method validation, specificity, linearity, precision and recovery parameters were verified. The concentration and area relationships were linear (R > 0.999), over the concentration ranges 20-120 μg mL for acetaminophen, 75-450 μg mL for dextromethorphan, 31.25-187.5 μg mL for doxylamine, 25-150 μg mL for phenylephrine, 25-150 μg mL for aspirin, 6.5-39 μg mL for caffeine and 12-72 μg mL for guaifenesin. The relative standard deviations for precision and intermediate precision were <1.5%. The proposed RP-HPLC generic method is applicable for routine analysis of cold and cough over-the-counter products.
Topics: Chromatography, High Pressure Liquid; Chromatography, Reverse-Phase; Drug Stability; Limit of Detection; Linear Models; Multi-Ingredient Cold, Flu, and Allergy Medications; Reproducibility of Results; Respiratory System Agents
PubMed: 31265736
DOI: 10.1002/bmc.4641 -
European Review For Medical and... Dec 2022
Reply Letter - to Urso et al "Comment on: Comparative dissolution profiles of two anti-emetic delayed release dosage forms of doxylamine and pyridoxine: Xonvea® tablets vs. Cariban® capsules".
Topics: Doxylamine; Pyridoxine; Antiemetics; Solubility; Ursodeoxycholic Acid; Tablets; Capsules; Gastrointestinal Agents; Delayed-Action Preparations
PubMed: 36524482
DOI: 10.26355/eurrev_202212_30533