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Journal of Hazardous Materials Aug 2024Ubiquitous distribution of pharmaceutical contaminants in environment has caused unexpected adverse effects on ecological organisms; however, how microorganisms recover...
Ubiquitous distribution of pharmaceutical contaminants in environment has caused unexpected adverse effects on ecological organisms; however, how microorganisms recover from their toxicities remains largely unknown. In this study, we comprehensively investigated the effect of a representative pollutant, doxylamine (DOX) on a freshwater microalgal species, Chlorella sp. by analyzing the growth patterns, biochemical changes (total chlorophyll, carotenoid, carbohydrate, protein, and antioxidant enzymes), and transcriptomics. We found toxicity of DOX on Chlorella sp. was mainly caused by disrupting synthesis of ribosomes in nucleolus, and r/t RNA binding and processing. Intriguingly, additional bicarbonate enhanced the toxicity of DOX with decreasing the half-maximum effective concentrations from 15.34 mg L to 4.63 mg L, which can be caused by inhibiting fatty acid oxidation and amino acid metabolism. Microalgal cells can recover from this stress via upregulating antioxidant enzymatic activities to neutralize oxidative stresses, and photosynthetic pathways and nitrogen metabolism to supply more energies and cellular signaling molecules. This study extended our understanding on how microalgae can recover from chemical toxicity, and also emphasized the effect of environmental factors on the toxicity of these contaminants on aquatic microorganisms.
Topics: Chlorella; Water Pollutants, Chemical; Transcriptome; Microalgae; Chlorophyll; Photosynthesis; Oxidative Stress; Carotenoids; Antioxidants
PubMed: 38815390
DOI: 10.1016/j.jhazmat.2024.134752 -
Journal of Analytical Toxicology May 2024In forensic toxicology, the pediatric population requires special focus when evaluating positive findings because of the many toxicokinetic and toxicodynamic differences...
In forensic toxicology, the pediatric population requires special focus when evaluating positive findings because of the many toxicokinetic and toxicodynamic differences (e.g., metabolic capabilities, body size, etc.) between the pediatric and adult populations. In particular, the administration of over-the-counter (OTC) medications needs careful consideration, as dosages given to the pediatric population (0 days - 18 years), particularly those given to individuals less than five years of age, tend to be lower than those given to individuals closer to adulthood. Postmortem pediatric data from eleven years (2010-2020) was compiled. A total of 1413 positive cases contained one or more of the following common OTC medications: antihistamines (brompheniramine, chlorpheniramine, diphenhydramine, doxylamine, and pheniramine), pain relievers (acetaminophen, naproxen, ibuprofen, and salicylates), cold/flu medications (dextro/levomethorphan, guaifenesin, ephedrine, and pseudoephedrine), gastrointestinal (GI) aids (dicyclomine and loperamide), and/or sleep aids (melatonin). Antihistamines, cold/flu medications, and pain relievers are the most common classes of drugs encountered in the postmortem pediatric population. To evaluate trends, three main age groups were created: ≤5 years old (5U, birth-5 years old), middle childhood (MC, 6-11 years old), and early adolescence (EA, 12-18 years old). When considering the data, it must be noted that many of these drugs may be co-administered in single and/or multi-drug formulations. In addition, some drugs may have a variety of uses, e.g., antihistamines may also be used as sleep aids. Of note, the prevalence of cases involving those aged 6-11 years old was far less than their younger and older pediatric counterparts. With the widespread availability of OTC medications, unintentional overdoses, recreational misuse, and suicidal overdoses can occur in the vulnerable, pediatric population.
PubMed: 38771225
DOI: 10.1093/jat/bkae042 -
American Family Physician Feb 2024Insomnia affects 30% of the U.S. population, with 5% to 15% meeting criteria for chronic insomnia. It can negatively impact quality of life, decrease productivity,...
Insomnia affects 30% of the U.S. population, with 5% to 15% meeting criteria for chronic insomnia. It can negatively impact quality of life, decrease productivity, increase fatigue and drowsiness, and put patients at higher risk of developing other health problems. Initial treatment focuses on nonpharmacologic therapies such as cognitive behavior therapy, which improves negative thought patterns and behaviors through sleep restriction, stimulus control, and relaxation techniques. Other nonpharmacologic treatments include exercise, mindfulness, and acupuncture. If these approaches are ineffective, pharmacologic agents may be considered. Medications such as benzodiazepines and Z-drugs are often prescribed for insomnia but should be avoided, if possible, due to short- and long-term risks associated with their use. Melatonin receptor agonists are safer and well tolerated but have limited effectiveness. Dual orexin receptor antagonists are effective in patients who have sleep maintenance insomnia or difficulty with sleep onset. Evidence for the use of antihistamines to treat insomnia is generally lacking, but doxylamine is effective for up to four weeks.
Topics: Adult; Humans; Sleep Initiation and Maintenance Disorders; Quality of Life; Benzodiazepines; Hypnotics and Sedatives; Sleep
PubMed: 38393799
DOI: No ID Found -
Annals of Internal Medicine Feb 2024
Topics: Female; Pregnancy; Humans; Doxylamine; Pyridoxine; Vomiting; Nausea; Drug Combinations; Acupuncture Therapy; Pregnancy Complications; Antiemetics
PubMed: 38373321
DOI: 10.7326/L23-0426 -
Annals of Internal Medicine Feb 2024
Topics: Female; Pregnancy; Humans; Doxylamine; Pyridoxine; Vomiting; Nausea; Drug Combinations; Acupuncture Therapy; Pregnancy Complications; Antiemetics
PubMed: 38373319
DOI: 10.7326/L23-0427 -
Annals of Internal Medicine Feb 2024
Topics: Female; Pregnancy; Humans; Doxylamine; Pyridoxine; Vomiting; Nausea; Drug Combinations; Acupuncture Therapy; Pregnancy Complications; Antiemetics
PubMed: 38373317
DOI: 10.7326/L23-0425 -
Geburtshilfe Und Frauenheilkunde Feb 2024Nausea and vomiting of pregnancy (NVP) is among the most common conditions that pregnant women encounter in the early stages of pregnancy. It can affect up to 85% of...
Nausea and vomiting of pregnancy (NVP) is among the most common conditions that pregnant women encounter in the early stages of pregnancy. It can affect up to 85% of pregnant women, thus representing a significant public health concern. NVP results in substantial negative physical, emotional, and financial consequences. Despite its prevalence, the pathogenesis remains elusive. Few guidelines have been published; however, several interventions exist for the symptomatic treatment of NVP. The aim of this review is to provide an overview of modern treatment strategies of NVP with a special focus on the recently approved dual-release formulation of the doxylamine and pyridoxine combination. This combination was approved by the Food and Drug Administration (FDA) in November 2016 for the treatment of NVP when conservative management fails, and it has been introduced to the American market in April 2018. The maximum plasma concentration (T ) of doxylamine and pyridoxal-5-phosphate is reached 3.5 h and 15 h, respectively, after administration of one tablet twice daily, or 4.5 h and 0.5 h, respectively, when one tablet is administered just once daily. In addition, the delayed-release combination allows sufficient levels of doxylamine and the active metabolite pyridoxal-5-phosphate in the systemic circulation, providing symptoms relief in the subsequent morning. Hence, the dual-release formulation can improve the quality of life of pregnant women suffering from NVP. Additionally, large epidemiological trials have shown no increased risk of adverse effects to newborns, demonstrating that its use is not teratogenic.
PubMed: 38344043
DOI: 10.1055/a-2225-5883 -
BJOG : An International Journal of... Jun 2024An objective and validated index of nausea and vomiting such as the Pregnancy-Unique Quantification of Emesis (PUQE) and HyperEmesis Level Prediction (HELP) tools can be...
An objective and validated index of nausea and vomiting such as the Pregnancy-Unique Quantification of Emesis (PUQE) and HyperEmesis Level Prediction (HELP) tools can be used to classify the severity of NVP and HG. [Grade C] Ketonuria is not an indicator of dehydration and should not be used to assess severity. [Grade A] There are safety and efficacy data for first line antiemetics such as anti (H1) histamines, phenothiazines and doxylamine/pyridoxine (Xonvea®) and they should be prescribed initially when required for NVP and HG (Appendix III). [Grade A] There is evidence that ondansetron is safe and effective. Its use as a second line antiemetic should not be discouraged if first line antiemetics are ineffective. Women can be reassured regarding a very small increase in the absolute risk of orofacial clefting with ondansetron use in the first trimester, which should be balanced with the risks of poorly managed HG. [Grade B] Metoclopramide is safe and effective and can be used alone or in combination with other antiemetics. [Grade B] Because of the risk of extrapyramidal effects metoclopramide should be used as second-line therapy. Intravenous doses should be administered by slow bolus injection over at least 3 minutes to help minimise these. [Grade C] Women should be asked about previous adverse reactions to antiemetic therapies. If adverse reactions occur, there should be prompt cessation of the medications. [GPP] Normal saline (0.9% NaCl) with additional potassium chloride in each bag, with administration guided by daily monitoring of electrolytes, is the most appropriate intravenous hydration. [Grade C] Combinations of different drugs should be used in women who do not respond to a single antiemetic. Suggested antiemetics for UK use are given in Appendix III. [GPP] Thiamine supplementation (either oral 100 mg tds or intravenous as part of vitamin B complex (Pabrinex®)) should be given to all women admitted with vomiting, or severely reduced dietary intake, especially before administration of dextrose or parenteral nutrition. [Grade D] All therapeutic measures should have been tried before considering termination of pregnancy. [Grade C].
Topics: Humans; Female; Pregnancy; Hyperemesis Gravidarum; Antiemetics; Ondansetron; Morning Sickness; Nausea; Pyridoxine; Metoclopramide; Severity of Illness Index; Pregnancy Complications
PubMed: 38311315
DOI: 10.1111/1471-0528.17739 -
Journal of Hazardous Materials Feb 2024Amine-based pharmaceuticals are a significant class of N-nitrosodimethylamine (NDMA) precursors. This study investigated the use of unactivated peroxymonosulfate (PMS)...
Amine-based pharmaceuticals are a significant class of N-nitrosodimethylamine (NDMA) precursors. This study investigated the use of unactivated peroxymonosulfate (PMS) to control amine-based pharmaceuticals and their NDMA formation potential. Kinetic analysis and product identification revealed that sumatriptan and doxylamine primarily underwent reactions at their tertiary amine group, while ranitidine and nizatidine had both tertiary amine and thioether group as reaction sites. The NDMA formation from sumatriptan and doxylamine during post-chloramination was significantly reduced with the abatement of the parent contaminants, while the formation of NDMA remained high even if full abatement of ranitidine and nizatidine was achieved. Product formation kinetics and reference standard tests revealed the great contribution of transformation products to NDMA formation. Ranitidine could be oxidized to sulfoxide-type product ranitidine-SO and N-oxide type product ranitidine-NO. Ranitidine-SO exhibited a high NDMA yield comparable to that of ranitidine (>90%), while ranitidine-NO showed a low NDMA yield (2%). With further oxidation of ranitidine-SO at the tertiary amine group, NDMA formation was reduced by more than 90%. The underlying mechanism for the importance of the tertiary amine group in NDMA formation was demonstrated by quantum chemical calculation. These findings underscore the potential of PMS pre-oxidation on NDMA control.
Topics: Amines; Ranitidine; Chloramines; Dimethylnitrosamine; Sumatriptan; Kinetics; Nizatidine; Doxylamine; Pharmaceutical Preparations; Water Purification; Water Pollutants, Chemical
PubMed: 37951171
DOI: 10.1016/j.jhazmat.2023.132961 -
Advances in Therapy Jan 2024Sleep deficit or poor sleep leads to ill-health, whereas sleep deprivation for longer periods of time increases the risk of developing adverse conditions associated with... (Randomized Controlled Trial)
Randomized Controlled Trial
Standardized Extract of Valeriana officinalis Improves Overall Sleep Quality in Human Subjects with Sleep Complaints: A Randomized, Double-Blind, Placebo-Controlled, Clinical Study.
INTRODUCTION
Sleep deficit or poor sleep leads to ill-health, whereas sleep deprivation for longer periods of time increases the risk of developing adverse conditions associated with poor quality of life, and high socioeconomic impact. The treatments for sleep disturbances include melatonin and over-the-counter medicines like diphenhydramine and doxylamine, all of which have negative side effects. Valerian (Valeriana officinalis L.) is a traditional herb and the most preferred alternate sleep solution to manage sleep complaints.
METHODS
Eighty adult subjects with sleep complaints were randomized in 1:1 ratio to receive either V. officinalis extract (VE) or placebo for 8 weeks in a double-blind, placebo-controlled, parallel, clinical study. Primary efficacy endpoints included the Pittsburgh Sleep Quality Index (PSQI) and sleep latency using wrist actigraphy (WA), as well as a number of secondary endpoints, including sleep parameters such as actual sleep time and sleep efficiency using WA, the Epworth Sleepiness Scale (ESS), the Beck Anxiety Inventory (BAI), the Visual Analogue Scale (VAS) for the feeling of waking up refreshed, and a tertiary endpoint of sleep parameters using polysomnography (PSG) in a subset of 20 subjects per group. Safety parameters included physical examination, vital sign measurements, hematology, and clinical chemistry tests. Adverse events and serious adverse events were monitored throughout the study period.
RESULTS
Seventy-two subjects (35 and 37 subjects in the placebo and VE groups, respectively) completed the study and were included in the efficacy assessments. On Days 14, 28, and 56, the PSQI Total Score in the VE group decreased significantly (p < 0.05) compared to the placebo group. Further, the VE group showed significant improvements (p < 0.05) in sleep latency and actual sleep time on Days 3, 14, 28, and 56, and sleep efficiency on Days 14, 28, and 56, as evaluated by WA. There was a decrease (p < 0.05) in anxiety (BAI) on Days 14, 28, and 56, daytime drowsiness (ESS) on Days 28 and 56, and an increased feeling of waking up refreshed (VAS) on Days 28 and 56 compared to placebo. PSG results carried out in subset of subjects revealed significant improvements (p < 0.05) in total sleep time, sleep latency, and sleep efficiency on Day 56 in the VE group compared to the placebo group. No safety concerns were observed throughout the study.
CONCLUSION
VE supplementation significantly improved various subjective and objective parameters of sleep in young subjects with mild insomnia symptoms, such as overall sleep quality, sleep latency, sleep efficiency, and total sleep time. We also observed decreased anxiety and daytime sleepiness, and improved feeling of being refreshed after waking up with VE supplementation. VE was found to be safe and well tolerated throughout the study.
TRIAL REGISTRATION
Clinical Trials Registry of India: CTRI/2022/05/042818.
Topics: Adult; Humans; Valerian; Sleep Quality; Quality of Life; Sleep; Sleep Initiation and Maintenance Disorders; Plant Extracts; Research Subjects; Double-Blind Method; Treatment Outcome
PubMed: 37899385
DOI: 10.1007/s12325-023-02708-6