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Pharmacoepidemiology and Drug Safety Jun 2024Methylphenidate (MPH) is a common treatment of attention-deficit/hyperactivity disorder (ADHD). Concern has been raised regarding its cardiovascular safety, partly in...
INTRODUCTION
Methylphenidate (MPH) is a common treatment of attention-deficit/hyperactivity disorder (ADHD). Concern has been raised regarding its cardiovascular safety, partly in relation with its micromolar affinity for the 5-HT receptor, whose activation may result in valvular heart disease (VHD).
METHODS
To explore the association between the use of MPH and VHD reporting, we performed a disproportionality analysis within the WHO global safety database (VigiBase) using data, since inception until March 6th 2024, from: (i) the full database and (ii) different age groups (children/adolescents 6-17 years; adults 18-64 years). To avoid competition bias, safety reports with amphetamine-like appetite suppressants were excluded. Disproportionality was expressed using reporting odds-ratio (ROR) and its 95% confidence interval (CI).
RESULTS
Of 29 129 spontaneous reports with MPH, 23 VHD cases (7.9 per 10 000 reports) were identified, including 13 adults and 10 children. Most cases concerned injury on the mitral valve. A disproportionate reporting was observed overall (ROR 1.6, 95% CI 1.1-2.4). Analysis according to age group found that disproportionality in VHD reporting was found in adults only (ROR 2.7, 95% CI 1.6-4.7) but not in children/adolescents (ROR 1.7, 95% CI 0.9-3.2). Furthermore, amongst MPH users only, VHD reporting was higher in adults compared to children (ROR 2.7, 95% CI 1.2-6.3).
CONCLUSION
VHD reporting appears rare with MPH compared to other adverse events and is increased in adults only. Our findings support a potential safety signal of VHD in adults exposed to MPH. A risk in that population cannot be excluded and requires further assessment.
Topics: Humans; Adolescent; Child; Pharmacovigilance; Heart Valve Diseases; Adult; Young Adult; Methylphenidate; Male; Central Nervous System Stimulants; Middle Aged; Female; Attention Deficit Disorder with Hyperactivity; Adverse Drug Reaction Reporting Systems; Databases, Factual; Age Factors
PubMed: 38837561
DOI: 10.1002/pds.5814 -
ACS Applied Materials & Interfaces Jun 2024A novel therapeutic approach combining acupuncture and diclofenac sodium (DS) administration was established for the potential treatment for rheumatoid arthritis (RA)....
A novel therapeutic approach combining acupuncture and diclofenac sodium (DS) administration was established for the potential treatment for rheumatoid arthritis (RA). DS is a commonly used anti-inflammatory and analgesic drug but has short duration and adverse effects. Acupoints are critical linkages in the meridian system and are potential candidates for drug delivery. Herein, we fabricated a DS-loaded multilayer-modified acupuncture needle (DS-MMAN) and investigated its capacity for inhibiting RA. This DS-MMAN possesses sustained release properties and anti-inflammatory effects. Experimental results showed that the DS-MMAN with microdoses can enhance analgesia and efficiently relieve joint swelling compared to the oral or intra-articular administration of DS with gram-level doses. Moreover, the combination of acupoint and DS exerts a synergistic improvement in inflammation and joint damage. Cytokine and T cell analyses in the serum indicated that the application of DS-MMAN suppressed the levels of pro-inflammatory factors and increased the levels of anti-inflammatory factors. Furthermore, the acupoint administration via DS-MMAN could decrease the accumulation of DS in the liver and kidneys, which may express better therapeutic efficiency and low toxicity. The present study demonstrated that the acupuncture needle has the potential to build a bridge between acupuncture and medication, which would be a promising alternative to the combination of traditional and modern medicine.
Topics: Diclofenac; Arthritis, Rheumatoid; Needles; Animals; Acupuncture Therapy; Mice; Male; Drug Delivery Systems; Humans; Anti-Inflammatory Agents, Non-Steroidal; Rats
PubMed: 38829728
DOI: 10.1021/acsami.4c04815 -
Marine Life Science & Technology May 2024Mutualistic interactions between marine phototrophs and associated bacteria are an important strategy for their successful survival in the ocean, but little is known...
UNLABELLED
Mutualistic interactions between marine phototrophs and associated bacteria are an important strategy for their successful survival in the ocean, but little is known about their metabolic relationships. Here, bacterial communities in the algal sphere (AS) and bulk solution (BS) of nine marine red algal cultures were analyzed, and and were identified significantly more abundantly in AS than in BS. The metabolic features of RMAR6-6 (isolated and genome-sequenced), MAG 12 (obtained by metagenomic sequencing), and a marine red alga, CCMP1328 (from GenBank), were analyzed bioinformatically. RMAR6-6 has the genetic capability to fix nitrogen and produce B vitamins (B1, B2, B5, B6, B9, and B12), bacterioferritin, dimethylsulfoniopropionate (DMSP), and phenylacetate that may enhance algal growth, whereas MAG 12 may have a limited metabolic capability, not producing vitamins B9 and B12, DMSP, phenylacetate, and siderophores, but with the ability to produce bacitracin, possibly modulating algal microbiome. . CCMP1328 lacks the genetic capability to fix nitrogen and produce vitamin B12, DMSP, phenylacetate, and siderophore. It was shown that the nitrogen-fixing ability of RMAR6-6 promoted the growth of . , and DMSP reduced the oxidative stress of . . The metabolic interactions between strain RMAR6-6 and . CCMP1328 were also investigated by the transcriptomic analyses of their monoculture and co-culture. Taken together, potential metabolic relationships between and . were proposed. This study provides a better understanding of the metabolic relationships between marine algae and algae-associated bacteria for successful growth.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s42995-024-00227-z.
PubMed: 38827136
DOI: 10.1007/s42995-024-00227-z -
International Journal of Pharmaceutics Jun 2024Neuropathic pain is chronic pain caused by a lesion or disease of the somatosensory nervous system. Neuropathic pain, with a high incidence and complex pathogenesis, is...
Neuropathic pain is chronic pain caused by a lesion or disease of the somatosensory nervous system. Neuropathic pain, with a high incidence and complex pathogenesis, is one of the most significant areas of clinical medicine and basic research. Currently, prescribed treatments are still unsatisfactory or have limited effectiveness. A medicinal preparation is required that relieves the neuropathic pain and prolongs action time, which has not yet been discovered. In this study, MIL-101 (Fe) was employed as a drug carrier to regulate the release of diclofenac sodium, thereby achieving the effect of analgesia and sustained release. The release curves demonstrated that diclofenac sodium could be continuously released from MIL-101 (Fe) for more than 48 h. There was no toxicity in vitro and in vivo, and the safety of MIL-101 (Fe) was confirmed by hematoxylin and eosin as well as ELISA tests in vivo. The results of behavioral testing, pharmacokinetics, and RNA sequencing analysis showed that MIL-101 (Fe) loaded with diclofenac sodium could enhance the mechanical withdrawal threshold and alleviate cold allodynia induced by Spared Nerve Injury, prolonging the work time by three days. The results indicated that MIL-101 (Fe) exhibited excellent biocompatibility, while the MIL-101 (Fe)-DS demonstrated analgesic and controlled-release properties. These findings provide a scientific foundation for the clinical management of neuropathic pain and the development of a novel formulation.
Topics: Animals; Diclofenac; Neuralgia; Male; Rats, Sprague-Dawley; Spinal Cord; Transcriptome; Nanomedicine; Rats; Drug Carriers; Anti-Inflammatory Agents, Non-Steroidal; Drug Liberation; Delayed-Action Preparations; Disease Models, Animal; Hyperalgesia
PubMed: 38821436
DOI: 10.1016/j.ijpharm.2024.124276 -
Growth Hormone & IGF Research :... Jun 2024To assess the growth hormone (GH) and Dopamine (DA) response to exercise in children with attention-deficit hyperactivity disorder (ADHD) with and without...
PURPOSE
To assess the growth hormone (GH) and Dopamine (DA) response to exercise in children with attention-deficit hyperactivity disorder (ADHD) with and without methylphenidate (MP). We hypothesized that the GH and DA response to the exercise with MP would be siginicantly lower.
METHODS
Twenty children participated in the study (12 males and 8 females, age range 9-13 years). Ten with ADHD and 10 controls. Participants with ADHD performed an exercise test twice, with and without MP while controls performed one exercise test. Blood samples for GH and DA were collected before, at peak, 30 and 60 min after the end of exercise.
RESULTS
Compared to controls, children with ADHD with and without MP, had a significantly lower GH (P < .002) and DA (P < .01) responses to exercise. In participants with ADHD, a significantly greater GH response (p < .04) to exercise was found when MP administered to the children before exercise, yet this response was still significantly lower than controls.
CONCLUSIONS
GH and DA excretion after an exercise challenge in children with ADHD is impaired. MP slightly attenuates the GH blunted response. This may link ADHD with growth impairment in some children and explain previous findings indicating that the final adult height is usually not compromised in children with ADHD treated with MP. The combined exercise and stimulant treatment therapeutic effects needs to be further explored.
TRIAL REGISTRATION NUMBER
NCT00945971.
Topics: Humans; Attention Deficit Disorder with Hyperactivity; Child; Methylphenidate; Female; Male; Adolescent; Exercise; Dopamine; Central Nervous System Stimulants; Human Growth Hormone; Case-Control Studies; Exercise Test
PubMed: 38820857
DOI: 10.1016/j.ghir.2024.101596 -
Journal of the American Chemical Society Jun 2024Catalytic π-arene activation is based on catalysts that allow for arene exchange. To date, cyclopentadiene (Cp)-derived catalysts are the most commonly used in π-arene...
Catalytic π-arene activation is based on catalysts that allow for arene exchange. To date, cyclopentadiene (Cp)-derived catalysts are the most commonly used in π-arene activation despite their low arene exchange rates. Herein, we report the synthesis, analysis, and catalytic application of Ru(II) complexes supported by phenoxo ligands, which are isolobal alternatives to Cp. The phenoxo complexes exhibit arene exchange rates significantly faster than those of the corresponding Cp complexes. The rate can be further increased through the choice of appropriate counterions. The mechanism of the arene exchange process is elucidated by kinetic and computational analyses. We demonstrate the utility of the new catalysts through an SAr reaction between fluorobenzene and alcohols, including secondary alcohols that could not be used previously in related reactions. Moreover, the catalytic thermal decarboxylation of phenylacetic acids is presented.
PubMed: 38819390
DOI: 10.1021/jacs.4c02088 -
Brain Research Sep 2024Traumatic brain injury (TBI) is a complex pathophysiological process that results in a variety of neurotransmitter, behavioral, and cognitive deficits. The locus...
Traumatic brain injury (TBI) is a complex pathophysiological process that results in a variety of neurotransmitter, behavioral, and cognitive deficits. The locus coeruleus-norepinephrine (LC-NE) system is a critical regulator of arousal levels and higher executive processes affected by TBI including attention, working memory, and decision making. LC-NE axon injury and impaired signaling within the prefrontal cortex (PFC) is a potential contributor to the neuropsychiatric symptoms after single, moderate to severe TBI. The majority of TBIs are mild, yet long-term cognitive deficits and increased susceptibility for further injury can accumulate after each repetitive mild TBI. As a potential treatment for restoring cognitive function and daytime sleepiness after injury psychostimulants, including methylphenidate (MPH) that increase levels of NE within the PFC, are being prescribed "off-label". The impact of mild and repetitive mild TBI on the LC-NE system remains limited. Therefore, we determined the extent of LC-NE and arousal dysfunction and response to therapeutic doses of MPH in rats following experimentally induced single and repetitive mild TBI. Microdialysis measures of basal NE efflux from the medial PFC and arousal measures were significantly lower after repetitive mild TBI. Females showed higher baseline PFC-NE efflux than males following single and repetitive mild TBI. In response to MPH challenge, males exhibited a blunted PFC-NE response and persistent arousal levels following repetitive mild TBI. These results provide critical insight into the role of catecholamine system dysfunction associated with cognitive deficits following repeated injury, outcome differences between sex/gender, and lack of success of MPH as an adjunctive therapy to improve cognitive function following injury.
Topics: Animals; Male; Norepinephrine; Female; Rats, Sprague-Dawley; Prefrontal Cortex; Central Nervous System Stimulants; Methylphenidate; Brain Concussion; Rats; Brain Injuries, Traumatic; Locus Coeruleus; Arousal; Microdialysis
PubMed: 38815643
DOI: 10.1016/j.brainres.2024.149040 -
Acta Pharmaceutica (Zagreb, Croatia) Jun 2024Oral solid dosage forms are most frequently administered with a glass of water which empties from the stomach relatively fast, but with a certain variability in its...
Oral solid dosage forms are most frequently administered with a glass of water which empties from the stomach relatively fast, but with a certain variability in its emptying kinetics. The purpose of this study was thus to simulate different individual water gastric emptying (GE) patterns in an glass-bead flow-through dissolution system. Further, the effect of GE on the dissolution of model drugs from immediate-release tablets was assessed by determining the amount of dissolved drug in the samples pumped out of the stomach compartment. Additionally, different HCl solutions were used as dissolution media to assess the effect of the variability of pH of the gastric fluid on the dissolution of three model drugs: paracetamol, diclofenac sodium, and dipyridamole. The difference in fast and slow GE kinetics resulted in different dissolution profiles of paracetamol in all studied media. For diclofenac sodium and dipyridamole tablets, the effect of GE kinetics was well observed only in media, where the solubility was not a limiting factor. Therefore, GE kinetics of co-ingested water influences the drug release from immediate-release tablets, however, in certain cases, other parameters influencing drug dissolution can partly or fully hinder the expression of this effect.
Topics: Gastric Emptying; Drug Liberation; Diclofenac; Water; Solubility; Tablets; Dipyridamole; Acetaminophen; Hydrogen-Ion Concentration; Kinetics; Administration, Oral; Glass
PubMed: 38815199
DOI: 10.2478/acph-2024-0016 -
Environmental Science and Pollution... Jun 2024This study presents a theoretical analysis of the adsorption process of pharmaceutical pollutants, specifically acetaminophen (ATP) and diclofenac (DFC), onto activated...
This study presents a theoretical analysis of the adsorption process of pharmaceutical pollutants, specifically acetaminophen (ATP) and diclofenac (DFC), onto activated carbon (AC) derived from avocado biomass waste. The adsorption isotherms of ATP and DFC were analyzed using a multilayer model, which revealed the formation of two to four adsorption layers depending on the temperature of the aqueous solution. The saturation adsorption capacities for ATP and DFC were 52.71 and 116.53 mg/g, respectively. A steric analysis suggested that the adsorption mechanisms of ATP and DFC involved a multi-molecular process. The calculated adsorption energies (ΔE and ΔE) varied between 12.86 and 22.58 kJ/mol, with the highest values observed for DFC removal. Therefore, the adsorption of these organic molecules was associated with physisorption interactions: van der Waals forces and hydrogen bonds. These findings enhance the understanding of the depollution processes of pharmaceutical compounds using carbon-based adsorbents and highlight the potential of utilizing waste biomass for environmental remediation.
Topics: Adsorption; Charcoal; Water Pollutants, Chemical; Diclofenac; Pharmaceutical Preparations; Carbon; Acetaminophen
PubMed: 38814558
DOI: 10.1007/s11356-024-33806-9 -
Annals of Medicine Dec 2024Tension-type headache is the most common type of primary headache and results in a huge socioeconomic burden. This network meta-analysis (NMA) aimed to compare the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Tension-type headache is the most common type of primary headache and results in a huge socioeconomic burden. This network meta-analysis (NMA) aimed to compare the efficacy and safety of simple analgesics for the treatment of episodic tension-type headache (ETTH) in adults.
METHODS
We searched the Cochrane Library, PubMed, Web of Science, Embase, Chinese BioMedical Literature database and International Clinical Trials Registry Platform databases for eligible randomized clinical trials reporting the efficacy and/or safety of simple analgesics. A Bayesian NMA was performed to compare relative efficacy and safety. The surface under the cumulative ranking curve (SUCRA) was calculated to rank interventions. PROSPERO registration number: CRD42018090554.
RESULTS
We highlighted six studies including 3507 patients. For the 2 h pain-free rate, the SUCRA ranking was ibuprofen > diclofenac-K > ketoprofen > acetaminophen > naproxen > placebo. All drugs except naproxen reported a higher 2 h pain-free rate than placebo, with a risk ratio (RR) of 2.86 (95% credible interval, CrI: 1.62-5.42) for ibuprofen and 2.61 (1.53-4.88) for diclofenac-K. For adverse events rate, the SUCRA ranking was: metamizol > diclofenac-K > ibuprofen > lumiracoxib > placebo > aspirin > acetaminophen > naproxen > ketoprofen. The adverse event rates of all analgesics were no higher than those of placebo, except for ketoprofen. Moreover, all drugs were superior to placebo in the global assessment of efficacy. In particular, the RR of lumiracoxib was 2.47 (1.57-4.57). Global heterogeneity between the studies was low.
CONCLUSIONS
Simple analgesics are considered more effective and safe as a placebo for ETTH in adults. Our results suggest that ibuprofen and diclofenac-K may be the two best treatment options for patients with ETTH from a comprehensive point of view (both high-quality evidence).
Topics: Humans; Tension-Type Headache; Analgesics; Adult; Network Meta-Analysis; Ibuprofen; Acetaminophen; Bayes Theorem; Treatment Outcome; Diclofenac; Randomized Controlled Trials as Topic; Naproxen; Ketoprofen; Anti-Inflammatory Agents, Non-Steroidal; Female; Male
PubMed: 38813682
DOI: 10.1080/07853890.2024.2357235