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The Science of the Total Environment Jan 2024Exposure to single molecules under laboratory conditions has led to a better understanding of the mechanisms of action (MeOAs) and effects of pharmaceutical active... (Review)
Review
Mixture effects of pharmaceuticals carbamazepine, diclofenac and venlafaxine on Mytilus galloprovincialis mussel probed by metabolomics and proteogenomics combined approach.
Exposure to single molecules under laboratory conditions has led to a better understanding of the mechanisms of action (MeOAs) and effects of pharmaceutical active compounds (PhACs) on non-target organisms. However, not taking the co-occurrence of contaminants in the environment and their possible interactions into account may lead to underestimation of their impacts. In this study, we combined untargeted metabolomics and proteogenomics approaches to assess the mixture effects of diclofenac, carbamazepine and venlafaxine on marine mussels (Mytilus galloprovincialis). Our multi-omics approach and data fusion strategy highlighted how such xenobiotic cocktails induce important cellular changes that can be harmful to marine bivalves. This response is mainly characterized by energy metabolism disruption, fatty acid degradation, protein synthesis and degradation, and the induction of endoplasmic reticulum stress and oxidative stress. The known MeOAs and molecular signatures of PhACs were taken into consideration to gain insight into the mixture effects, thereby revealing a potential additive effect. Multi-omics approaches on mussels as sentinels offer a comprehensive overview of molecular and cellular responses triggered by exposure to contaminant mixtures, even at environmental concentrations.
Topics: Animals; Mytilus; Diclofenac; Venlafaxine Hydrochloride; Proteogenomics; Water Pollutants, Chemical; Carbamazepine; Benzodiazepines; Pharmaceutical Preparations
PubMed: 37879482
DOI: 10.1016/j.scitotenv.2023.168015 -
Translational Psychiatry Mar 2024Psychotic depression is a severe and difficult-to-treat subtype of major depressive disorder for which higher rates of treatment-resistant depression were found. Studies... (Randomized Controlled Trial)
Randomized Controlled Trial
Psychotic depression is a severe and difficult-to-treat subtype of major depressive disorder for which higher rates of treatment-resistant depression were found. Studies have been performed aiming to predict treatment-resistant depression or treatment nonresponse. However, most of these studies excluded patients with psychotic depression. We created a genetic risk score (GRS) based on a large treatment-resistant depression genome-wide association study. We tested whether this GRS was associated with nonresponse, nonremission and the number of prior adequate antidepressant trials in patients with a psychotic depression. Using data from a randomized clinical trial with patients with a psychotic depression (n = 122), we created GRS deciles and calculated positive prediction values (PPV), negative predictive values (NPV) and odds ratios (OR). Nonresponse and nonremission were assessed after 7 weeks of treatment with venlafaxine, imipramine or venlafaxine plus quetiapine. The GRS was negatively correlated with treatment response (r = -0.32, p = 0.0023, n = 88) and remission (r = -0.31, p = 0.0037, n = 88), but was not correlated with the number of prior adequate antidepressant trials. For patients with a GRS in the top 10%, we observed a PPV of 100%, a NPV of 73.7% and an OR of 52.4 (p = 0.00072, n = 88) for nonresponse. For nonremission, a PPV of 100%, a NPV of 51.9% and an OR of 21.3 (p = 0.036, n = 88) was observed for patients with a GRS in the top 10%. Overall, an increased risk for nonresponse and nonremission was seen in patients with GRSs in the top 40%. Our results suggest that a treatment-resistant depression GRS is predictive of treatment nonresponse and nonremission in psychotic depression.
Topics: Humans; Depressive Disorder, Major; Venlafaxine Hydrochloride; Depression; Genetic Risk Score; Genome-Wide Association Study; Antidepressive Agents; Treatment Outcome
PubMed: 38431658
DOI: 10.1038/s41398-024-02842-x -
Neuropsychopharmacology : Official... Sep 2023Brain metabolism is a fundamental process involved in the proper development of the central nervous system and in the maintenance of the main higher functions in humans....
Brain metabolism is a fundamental process involved in the proper development of the central nervous system and in the maintenance of the main higher functions in humans. As consequence, energy metabolism imbalance has been commonly associated to several mental disorders, including depression. Here, by employing a metabolomic approach, we aimed to establish if differences in energy metabolite concentration may underlie the vulnerability and resilience in an animal model of mood disorder named chronic mild stress (CMS) paradigm. In addition, we have investigated the possibility that modulation of metabolite concentration may represent a pharmacological target for depression by testing whether repeated treatment with the antidepressant venlafaxine may normalize the pathological phenotype by acting at metabolic level. The analyses were conducted in the ventral hippocampus (vHip) for its key role in the modulation of anhedonia, a core symptom of patients affected by depression. Interestingly, we showed that a shift from glycolysis to beta oxidation seems to be responsible for the vulnerability to chronic stress and that vHip metabolism contributes to the ability of the antidepressant venlafaxine to normalize the pathological phenotype, as shown by the reversal of the changes observed in specific metabolites. These findings may provide novel perspectives on metabolic changes that could serve as diagnostic markers and preventive strategies for the early detection and treatment of depression as well as for the identification of potential drug targets.
Topics: Rats; Animals; Humans; Venlafaxine Hydrochloride; Rats, Wistar; Glucose; Antidepressive Agents; Anhedonia; Hippocampus; Stress, Psychological; Depression; Disease Models, Animal
PubMed: 37380799
DOI: 10.1038/s41386-023-01633-0 -
Dermatology Practical & Conceptual Jul 2023Primary erythromelalgia (EM) is a rare clinical syndrome characterized by recurrent erythema, burning pain and warmth of the extremities. The symptoms greatly compromise...
INTRODUCTION
Primary erythromelalgia (EM) is a rare clinical syndrome characterized by recurrent erythema, burning pain and warmth of the extremities. The symptoms greatly compromise the patients' quality of life leading to severe disability. SCN9A mutations can be the cause of the disease. Dermatologists are often the specialists these patients turn to for assistance.
OBJECTIVES
To describe the demographic and clinical characteristics of patients with primary EM, to assess the presence and mutation types in the SCN9A gene, to evaluate the effectiveness of several therapeutic approaches, and to propose a diagnostic algorithm with therapeutic implications.
METHODS
A monocentric retrospective study using the database of patients with a discharge diagnosis of primary EM of our Center. Demographic, clinical, instrumental and laboratory data of patients were reviewed.
RESULTS
Eleven female patients (age range 16 to 57) were selected. All patients were affected in both the lower and upper extremities. Follow-up ranged from 2 to 9 years. Four patients had four different heterozygous variants of the SCN9A gene. Two patients, although genetically negative, had a suggestive family history. A variety of medications were tried in all our patients to alleviate symptoms, but their efficacy was variable, partial and/or transitory. The most effective therapies were antihistamines, venlafaxine, and mexiletine.
CONCLUSIONS
The diagnosis and treatment of EM remain challenging. Patients with this condition display a wide spectrum of clinical manifestations and severity, as well as a paucity of resources and structures to support them. Mutations in the SCN9A gene are not always detected.
PubMed: 37557164
DOI: 10.5826/dpc.1303a191 -
Advances in Pharmacological and... 2024Depression affects an estimated 350 million people worldwide and is implicated in up to 60% of suicides. Only about 60-70% of patients respond to antidepressant therapy....
INTRODUCTION
Depression affects an estimated 350 million people worldwide and is implicated in up to 60% of suicides. Only about 60-70% of patients respond to antidepressant therapy. One of the factors causing patients to not attain therapeutic goals is herb-drug interactions.
OBJECTIVE
To investigate any potential herb-drug interaction that might exist between extract (XAE) or xylopic acid (XA) and selected conventional antidepressants (imipramine, fluoxetine, and venlafaxine) in mice.
METHODS
Dried, powdered fruits of were cold macerated in 70% ethanol to obtain XAE. XA was isolated by cold macerating dried fruits of in petroleum ether, crystallising impure XA with ethyl acetate, and purifying XA crystals with 96% ethanol. Pharmacodynamic interaction was assessed via isobolographic analysis of tail suspension tests of the agents individually and in their respective combinations. Pharmacokinetic interaction was assessed by monitoring the effect of coadministrations on the plasma concentration of antidepressants and xylopic acid via HPLC analysis.
RESULTS
XAE and XA in mice showed significant antidepressant-like activity in the tail suspension test. With interaction indices less than one, synergism of antidepressant effect was observed in the extract/fluoxetine ( = 0.502), extract/imipramine ( = 0.322), extract/venlafaxine ( = 0.601), xylopic acid/imipramine ( = 0.556), xylopic acid/venlafaxine ( = 0.451), and xylopic acid/fluoxetine ( = 0.298) combinations, which may be potentially due to elevation of serotonergic neurotransmission via varying mechanisms. The AUC of imipramine (AUC = 1966 ± 58.98 g/ml.h) was significantly ( < 0.0001) reduced by extract (AUC = 1228 ± 67.40 g/ml.h) and xylopic acid (AUC = 1250 ± 55.95 g/ml.h), while the AUC of xylopic acid (AUC = 968.10 ± 61.22 g/ml.h) was significantly ( < 0.0001) reduced by venlafaxine (AUC = 285.90 ± 51.92 g/ml.h) and fluoxetine (AUC = 510.60 ± 44.74 g/ml.h), possibly due to the effect of interfering agents on gastric emptying hence reducing oral absorption.
CONCLUSION
extract and xylopic acid interacted synergistically with imipramine, fluoxetine, and venlafaxine and reduced the systemic circulation of imipramine.
PubMed: 38826835
DOI: 10.1155/2024/9923801 -
Current Therapeutic Research, Clinical... 2023Intranasal administration is among the most effective alternatives to deliver drugs directly to the brain and prevent first-pass metabolism. Venlafaxine-loaded liposomes...
BACKGROUND
Intranasal administration is among the most effective alternatives to deliver drugs directly to the brain and prevent first-pass metabolism. Venlafaxine-loaded liposomes are biocompatible carriers that enhance transport qualities over the nasal mucosa.
OBJECTIVE
This research aimed to develop, formulate, characterize, and observe the prepared formulation.
METHODS
The formulation was developed using the thin-film hydration technique. The response surface plot interrelationship between three independent variables are lipid, cholesterol and polymer and four dependent variables such as particle size, percentage entrapment efficiency, and percentage drug release were ascertained using the Box-Behnken design.
RESULTS
The drug-release chitosan-coated liposomes were reported to have a particle size distribution, entanglement efficiency, and 84%, respectively, of 191 ± 34.71 nm, 94 ± 2.71% and 94 ± 2.71%. According to investigations, liposomes as a delivery system for the nasal route provided a more sustained drug release than the oral dosing form.
CONCLUSIONS
The intranasal administration of venlafaxine liposomal vesicles effectively enhanced the absolute bioavailability, retention time, and brain delivery of venlafaxine.
PubMed: 37727460
DOI: 10.1016/j.curtheres.2023.100714 -
The Science of the Total Environment Feb 2024Plastic pollution is an increasing environmental concern. Pollutants such as microplastics (< 5 mm) and pharmaceuticals often co-exist in the aquatic environment. The...
Plastic pollution is an increasing environmental concern. Pollutants such as microplastics (< 5 mm) and pharmaceuticals often co-exist in the aquatic environment. The current study aimed to elucidate the interaction of pharmaceuticals with microplastics and ascertain how the process of photo-oxidation of microplastics affected the adsorption of the pharmaceuticals. To this end, a mixture containing ibuprofen, carbamazepine, fluoxetine, venlafaxine and ofloxacin (16 μmol L each) was placed in contact with one of six either virgin or aged microplastic types. The virgin microplastics were acquired commercially and artificially aged in the laboratory. Polypropylene, polyethylene, polyethylene terephthalate, polyamide, polystyrene, and polyvinyl chloride microparticles at two sizes described as small (D < 35 μm) and large (D 95-157 μm) were evaluated. Results demonstrated that the study of virgin particles may underestimate the adsorption of micropollutants onto microplastics. For virgin particles, only small microparticles of polypropylene, polyethylene, polyvinyl chloride, and both sizes of polyamide adsorbed pharmaceuticals. Aging the microplastics increased significantly the adsorption of pharmaceuticals by microplastics. Fluoxetine adsorbed onto all aged microplastics, from 18 % (large polyethylene terephthalate) to 99 % (small polypropylene). The current investigation highlights the potential of microplastics to act as a vector for pharmaceuticals in freshwater, especially after aging.
Topics: Microplastics; Plastics; Polypropylenes; Polyethylene Terephthalates; Nylons; Adsorption; Polyvinyl Chloride; Fluoxetine; Water Pollutants, Chemical; Fresh Water; Polyethylene; Pharmaceutical Preparations
PubMed: 38141976
DOI: 10.1016/j.scitotenv.2023.169467 -
PeerJ 2024Stress profoundly impacts various aspects of both physical and psychological well-being. Our previous study demonstrated that venlafaxine (Vlx) and synbiotic (Syn)...
Stress profoundly impacts various aspects of both physical and psychological well-being. Our previous study demonstrated that venlafaxine (Vlx) and synbiotic (Syn) treatment attenuated learned fear-like behavior and recognition memory impairment in immobilized-stressed rats. In this study, we further investigated the physical, behavior, and cellular mechanisms underlying the effects of Syn and/or Vlx treatment on brain and intestinal functions in stressed rats. Adult male Wistar rats, aged 8 weeks old were subjected to 14 days of immobilization stress showed a decrease in body weight gain and food intake as well as an increase in water consumption, urinary corticosterone levels, and adrenal gland weight. Supplementation of Syn and/or Vlx in stressed rats resulted in mitigation of weight loss, restoration of normal food and fluid intake, and normalization of corticosterone levels. Behavioral analysis showed that treatment with Syn and/or Vlx enhanced depressive-like behaviors and improved spatial learning-memory impairment in stressed rats. Hippocampal dentate gyrus showed stress-induced neuronal cell death, which was attenuated by Syn and/or Vlx treatment. Stress-induced ileum inflammation and increased intestinal permeability were both effectively reduced by the supplementation of Syn. In addition, Syn and Vlx partly contributed to affecting the expression of the glial cell-derived neurotrophic factor in the hippocampus and intestines of stressed rats, suggesting particularly protective effects on both the gut barrier and the brain. This study highlights the intricate interplay between stress physiological responses in the brain and gut. Syn intervention alleviate stress-induced neuronal cell death and modulate depression- and memory impairment-like behaviors, and improve stress-induced gut barrier dysfunction which were similar to those of Vlx. These findings enhance our understanding of stress-related health conditions and suggest the synbiotic intervention may be a promising approach to ameliorate deleterious effects of stress on the gut-brain axis.
Topics: Male; Animals; Rats; Rats, Wistar; Venlafaxine Hydrochloride; Corticosterone; Synbiotics; Cognition
PubMed: 38435986
DOI: 10.7717/peerj.17033 -
Drugs associated with a risk of supraventricular tachycardia: analysis using the OpenVigil database.The Journal of International Medical... Mar 2024The OpenVigil database can be used to assess medications that may cause supraventricular tachycardia (SVT) and to produce a reference for their safe use in clinical...
OBJECTIVE
The OpenVigil database can be used to assess medications that may cause supraventricular tachycardia (SVT) and to produce a reference for their safe use in clinical settings.
METHODS
We analyzed first-quarter data from 2004 to 2023, obtained by searching the OpenVigil database using the keyword "supraventricular tachycardia." Trade names and generic names were obtained by querying the RxNav database, and the proportions were summarized. The proportionate reporting ratio (PRR), reporting odds ratio, and chi-square values were also summarized. We created Asahi diagrams and set the screening criteria to drug events ≥30, PRR >2, and chi-square >4. Outcomes were evaluated using the Side Effect Resource database, several scientific literature databases, and the Hangzhou Yiyao Rational Medication System.
RESULTS
A total of 2435 distinct medications were found to induce SVT between the first quarter of 2004 and 2023, leading to 22,375 documented adverse events related to SVT. Further investigation revealed that salbutamol, paroxetine, formoterol, paclitaxel, venlafaxine, and theophylline were most likely to cause SVT.
CONCLUSION
We conducted signal mining of adverse drug events using the OpenVigil database and evaluated the six drugs most likely to cause SVT. The results of this research can serve as a drug safety reference in the clinic.
Topics: Humans; Tachycardia, Supraventricular; Albuterol; Databases, Factual; Drug-Related Side Effects and Adverse Reactions; Formoterol Fumarate
PubMed: 38530149
DOI: 10.1177/03000605241238077 -
Cureus Oct 2023Serotonin syndrome (SS) is an entity caused by interference with the serotonin metabolism and/or by medications that act as serotonin receptor agonists. The signs and...
Serotonin syndrome (SS) is an entity caused by interference with the serotonin metabolism and/or by medications that act as serotonin receptor agonists. The signs and symptoms are nonspecific, making the diagnosis challenging. Treatment depends on the severity of the manifestations. In mild to moderate cases, it typically resolves within the first 24 hours after initiating therapy and discontinuation of the serotoninergic medications. A 42-year-old woman with a previous history of depression was admitted to the hospital due to the voluntary ingestion of multiple tablets of escitalopram 10 mg and venlafaxine 75 mg. Physical examination showed a hyperthermic and diaphoretic patient. Tremor, agitation, bilateral ocular clonus, and spontaneous inferior limb clonus were also present. Hunter's criteria were applied, and the diagnosis of SS was assumed. Supportive and symptomatic treatments were initiated. The evolution was benign, with symptomatic remission in the first 24 hours. In the last decades, a large increase in the use of antidepressants was noted, and, as such, defining SS as rare is no longer appropriate. Delaying the treatment can dictate an increase in morbidity and mortality. It is important to highlight that the diagnosis is mainly clinical as diagnostic criteria may miss out on some cases. As such, clinical awareness of SS's multiplicity of presentations is of utmost importance.
PubMed: 38021488
DOI: 10.7759/cureus.47470