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Pediatric Nephrology (Berlin, Germany) Jun 2023Valproic acid is prescribed for epilepsy and as prophylaxis for bipolar disorder and migraine headaches. It has also been implicated as a cause of a kidney tubular... (Review)
Review
BACKGROUND
Valproic acid is prescribed for epilepsy and as prophylaxis for bipolar disorder and migraine headaches. It has also been implicated as a cause of a kidney tubular injury.
METHODS
We undertook a review of the literature to characterize the biochemical and histopathological features of the overt kidney tubular injury and to evaluate the possible existence of a pauci-symptomatic injury. The pre-registered review (CRD42022360357) was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. Searches were conducted in Excerpta Medica, the National Library of Medicine, and Web of Science. The gray literature was also considered.
RESULTS
For the final analysis, we retained 36 articles: 28 case reports documented 48 individuals with epilepsy on valproic acid for 7 months or more and presenting with features consistent with an overt kidney tubular injury. The following disturbances were noted: hypophosphatemia (N = 46), normoglycemic glycosuria (N = 46), total proteinuria (N = 45), metabolic acidosis (N = 36), hypouricemia (N = 27), tubular proteinuria (N = 27), hypokalemia (N = 23), and hypocalcemia (N = 8). A biopsy, obtained in six cases, disclosed altered proximal tubular cells with giant and dysmorphic mitochondria. Eight case series addressed the existence of a pauci- or even asymptomatic kidney injury. In the reported 285 subjects on valproic acid for 7 months or more, an isolated tubular proteinuria, mostly N-acetyl-β-glucosaminidase, was often noted.
CONCLUSIONS
Valproic acid may induce an overt kidney tubular injury, which is associated with a proximal tubular mitochondrial toxicity. Treatment for 7 months or more is often associated with a pauci- or oligosymptomatic kidney tubular injury. A higher resolution version of the Graphical abstract is available as Supplementary information.
Topics: Humans; Valproic Acid; Kidney Tubules, Proximal; Kidney; Proteinuria; Epilepsy
PubMed: 36645492
DOI: 10.1007/s00467-022-05869-8 -
Frontiers in Pharmacology 2022Treatment of chemotherapy-induced peripheral neuropathy (CIPN) is challenging for clinicians, and many clinical trials and meta-analyses on CIPN are controversial....
Treatment of chemotherapy-induced peripheral neuropathy (CIPN) is challenging for clinicians, and many clinical trials and meta-analyses on CIPN are controversial. There are also few comparisons of the efficacy among drugs used to treat CIPN. Therefore, this systematic review aimed to study the efficacy of drugs in treating CIPN using existing randomized controlled trials. Electronic databases were searched for randomized controlled trials (RCTs) involving any pharmaceutical intervention and/or combination therapy of treating CIPN. Seventeen RCTs investigating 16 drug categories, duloxetine, pregabalin, crocin, tetrodotoxin, venlafaxine, monosialotetrahexosyl ganglioside (GM1), lamotrigine, KA (ketamine and amitriptyline) cream, nortriptyline, amitriptyline, topical (bitter apple) oil, BAK (baclofen, amitriptyline hydrochloride, and ketamine) pluronic lecithin organogel, gabapentin, and acetyl l-carnitine (ALC), in the treatment of CIPN were retrieved. Many of the included RCTs consisted of small sample sizes and short follow-up periods. It was difficult to quantify due to the highly variable nature of outcome indicators. Duloxetine, venlafaxine, pregabalin, crocin, tetrodotoxin, and monosialotetrahexosyl ganglioside exhibited some beneficial effects in treating CIPN. Duloxetine, GM1, and crocin showed moderate benefits based on the evidence review, while lamotrigine, KA cream, nortriptyline, amitriptyline, and topical (bitter apple) oil were not beneficial. Further studies were necessary to confirm the efficacy of gabapentin in the treatment of CIPN because of the controversy of efficacy of gabapentin. Furthermore, BAK topicalcompound analgesic gel only had a tendency to improve the CIPN symptoms, but the difference was not statistically significant. ALC might result in worsening CIPN. Most studies were not of good quality because of small sample sizes. Therefore, standardized randomized controlled trials with large samples were needed to critically assess the effectiveness of these drugs in treating CIPN in the future.
PubMed: 36618919
DOI: 10.3389/fphar.2022.1080888 -
Frontiers in Cardiovascular Medicine 2022Endothelial-mesenchymal transition (EndMT) is a differentiation process in which endothelial cells lose their own characteristics and acquire mesenchymal-like...
Endothelial-mesenchymal transition (EndMT) is a differentiation process in which endothelial cells lose their own characteristics and acquire mesenchymal-like characteristics, which contributes to the formation and development of atherosclerotic plaques. Until now, there is still a lack of effective measures to treat atherosclerosis (AS), so there is an urgent need to understand the underlying mechanisms of AS. In addition, although various studies have shown that EndMT is involved in the pathological stages of cardiovascular diseases, such as myocardial fibrosis, myocardial hypertrophy, and hypertension, the specific molecular mechanisms driving EndMT are still in the exploratory stage. In this review, we review the role of histone modifications (methylation, demethylation and acetylation, deacetylation) on EndMT in cardiovascular disease, aiming to target histone-modifying enzymes to guide cardiovascular disease therapy.
PubMed: 36568553
DOI: 10.3389/fcvm.2022.1022988 -
Archives of Gynecology and Obstetrics Sep 20237-Keto-DHEA has been commercially advertised as a dietary supplement to support weight loss. The objective of the present systematic review it to summarize the evidence... (Review)
Review
7-Keto-DHEA has been commercially advertised as a dietary supplement to support weight loss. The objective of the present systematic review it to summarize the evidence supporting the use of 7-keto-DHEA in overweight and obese population. The systematic search was conducted in Medline, Embase, Cochrane Library, CINAHL, Web of Science, Scopus, ICTRP, and ClinicalTrials.gov. Additionally, reference lists of eligible studies were considered, and authors of relevant studies were contacted. Two authors independently screened the studies against the inclusion criteria and assessed their risk of bias. In total, 4 out of 686 studies were included in the review. They all held a low risk of bias. Half of them showed a significant reduction in body weight. One study found a decrease in body fat percentage and another one reported a decrease in BMI. Two studies stated an increase in resting metabolic rate. No serious adverse effects were reported. Various possible mechanisms in favor of weight loss are discussed; however, with the evidence currently available, no clear answer can be given regarding 7-keto-DHEA and weight loss. Further studies need to be conducted to clarify the efficacy and safety of this drug before it can be recommended for therapeutic use.
Topics: Humans; Body Weight; Obesity; Overweight; Weight Loss
PubMed: 36566478
DOI: 10.1007/s00404-022-06884-8 -
Antioxidants (Basel, Switzerland) Nov 2022Sustained TB infection overproduces reactive oxygen species (ROS) as a host defense mechanism. Research shows ROS is destructive to lung tissue. Glutathione (GSH)... (Review)
Review
Sustained TB infection overproduces reactive oxygen species (ROS) as a host defense mechanism. Research shows ROS is destructive to lung tissue. Glutathione (GSH) neutralizes ROS, although it is consumed. NAC is a precursor of GSH synthesis, and administering an appropriate dose of NAC to patients with respiratory conditions may enhance lung recovery and replenish GSH. The present review searched for articles reporting on the effects of NAC in TB treatment from 1960 to 31 May 2022. The PICO search strategy was used in Google Scholar, PubMed, SciFinder, and Wiley online library databases. The COVIDENCE tool was used to delete inappropriate content. We eventually discovered five clinical trials, one case report, seven reviews, in vitro research, and four experimental animal studies from the twenty-four accepted articles. The use of NAC resulted in increased GSH levels, decreased treatment time, and was safe with minimal adverse events. However, the evidence is currently insufficient to estimate the overall effects of NAC, thus the study warrants more NAC clinical trials to demonstrate its effects in TB treatment.
PubMed: 36421484
DOI: 10.3390/antiox11112298 -
Frontiers in Nutrition 2022When mild traumatic brain injury (mTBI) occurs following an impact on the head or body, the brain is disrupted leading to a series of metabolic events that may alter the...
UNLABELLED
When mild traumatic brain injury (mTBI) occurs following an impact on the head or body, the brain is disrupted leading to a series of metabolic events that may alter the brain's ability to function and repair itself. These changes may place increased nutritional demands on the body. Little is known on whether nutritional interventions are safe for patients to implement post mTBI and whether they may improve recovery outcomes. To address this knowledge gap, we conducted a systematic review to determine what nutritional interventions have been prescribed to humans diagnosed with mTBI during its acute period (<14 days) to support, facilitate, and result in measured recovery outcomes.
METHODS
Databases CINAHL, PubMed, SPORTDiscus, Web of Science, and the Cochrane Library were searched from inception until January 6, 2021; 4,848 studies were identified. After removing duplicates and applying the inclusion and exclusion criteria, this systematic review included 11 full papers.
RESULTS
Patients that consumed enough food to meet calorie and macronutrient (protein) needs specific to their injury severity and sex within 96 h post mTBI had a reduced length of stay in hospital. In addition, patients receiving nutrients and non-nutrient support within 24-96 h post mTBI had positive recovery outcomes. These interventions included omega-3 fatty acids (DHA and EPA), vitamin D, mineral magnesium oxide, amino acid derivative -acetyl cysteine, hyperosmolar sodium lactate, and nootropic cerebrolysin demonstrated positive recovery outcomes, such as symptom resolution, improved cognitive function, and replenished nutrient deficiencies (vitamin D) for patients post mTBI.
CONCLUSION
Our findings suggest that nutrition plays a positive role during acute mTBI recovery. Following mTBI, patient needs are unique, and this review presents the potential for certain nutritional therapies to support the brain in recovery, specifically omega-3 fatty acids. However, due to the heterogenicity nature of the studies available at present, it is not possible to make definitive recommendations.
SYSTEMATIC REVIEW REGISTRATION
The systematic review conducted following the PRISMA guidelines protocol was registered (CRD42021226819), on Prospero.
PubMed: 36313085
DOI: 10.3389/fnut.2022.977728 -
Chronic Stress (Thousand Oaks, Calif.) 2022A stressor-related disorder wherein traumatic experience precipitates protracted disruptions to mood and cognition, post-traumatic stress disorder (PTSD) is associated... (Review)
Review
A stressor-related disorder wherein traumatic experience precipitates protracted disruptions to mood and cognition, post-traumatic stress disorder (PTSD) is associated with wide-ranging abnormalities across the body. While various methods have investigated these deviations, only proton magnetic resonance spectroscopy (H MRS) enables noninvasive measurement of small-molecule metabolites in the living human. H MRS has correspondingly been employed to test hypotheses about the composition and function of multiple brain regions putatively involved in PTSD. Here we systematically review methodological considerations and reported findings, both positive and negative, of the current H-MRS literature in PTSD (N = 32 studies) to communicate the brain regional metabolite alterations heretofore observed, providing random-effects model meta-analyses for those most extensively studied. Our review suggests significant PTSD-associated decreases in N-acetyl aspartate in bilateral hippocampus and anterior cingulate cortex with less evident effect in other metabolites and regions. Model heterogeneities diverged widely by analysis (I < 0.01% to 90.1%) and suggested regional dependence on quantification reference (creatine or otherwise). While observed variabilities in methods and reported findings suggest that H-MRS explorations of PTSD could benefit from methodological standardization, informing this standardization by quantitative assessment of the existing literature is currently hampered by its small size and limited scope.
PubMed: 36237981
DOI: 10.1177/24705470221128004 -
Therapeutic Advances in Neurological... 2022The safety and efficacy of hyperacute reperfusion therapies in childhood stroke due to focal cerebral arteriopathy (FCA) with an infectious and inflammatory component is...
The safety and efficacy of hyperacute reperfusion therapies in childhood stroke due to focal cerebral arteriopathy (FCA) with an infectious and inflammatory component is unknown. Lyme neuroborreliosis (LNB) is reported as a rare cause of childhood stroke. Intravenous thrombolysis (IVT) and endovascular therapy (EVT) have not been reported in LNB-associated stroke in children. We report two children with acute stroke associated with LNB who underwent hyperacute stroke treatment. A systematic review of the literature was performed to identify case reports of LNB-associated childhood stroke over the last 20 years. Patient 1 received IVT within 73 min after onset of acute hemiparesis and dysarthria; medulla oblongata infarctions were diagnosed on magnetic resonance imaging (MRI). Patient 2 received successful EVT 6.5 hr after onset of progressive tetraparesis, coma, and decerebrate posturing caused by basilar artery occlusion with bilateral pontomesencephalic infarctions. Both patients exhibited a lymphocytic cerebrospinal fluid (CSF) pleocytosis and elevated antibody index (AI) to . Antibiotic treatment, steroids, and platelet inhibitors including tirofiban infusion in patient 2 were administered. No side effects were observed. On follow-up, patient 1 showed good recovery and patient 2 was asymptomatic. In the literature, 12 cases of LNB-associated childhood stroke were reported. LNB-associated infectious and inflammatory FCA is not a medical contraindication for reperfusion therapies in acute childhood stroke. Steroids are discussed controversially in inflammatory FCA due to LNB. Intensified antiplatelet regimes may be considered; secondary prophylaxis with acetyl-salicylic acid (ASA) is recommended because of a high risk of early stroke recurrence.
PubMed: 36061261
DOI: 10.1177/17562864221102842 -
Fish & Shellfish Immunology Nov 2022Nanoparticles-based treatments is of utmost importance for aquaculture. In this scenario, chitosan-based nanoparticles have been proposed due to the properties of... (Review)
Review
Nanoparticles-based treatments is of utmost importance for aquaculture. In this scenario, chitosan-based nanoparticles have been proposed due to the properties of chitosan, which include mucoadhesiveness. Nevertheless, pivotal parameters of chitosan, such as degree of acetylation and molecular weight, are commonly underestimated in the available literature despite the influence they seem to have on the properties of chitosan-based nanoparticles. In this systematic review, the immunomodulator capacity of chitosan nanoparticles used as mucosal vaccines on teleost fish has been evaluated paying special attention to the chitosan properties. Four databases were used for literature search, yielding 486 documents, from which 14 meet the inclusion criteria. Only 21% of the available studies reported properly chitosan properties, which should be improved in future works to generate reproducible data as well as valuable information. To the best of our knowledge, this work objectively compares for the first time, by quantifying the mg of chitosan/g of fish applied in each study, the chitosan nanoparticle preparation and doses applied to fish, as well as the effects of the treatments applied on fish immune status.
Topics: Adjuvants, Immunologic; Animals; Chitosan; Immunity, Mucosal; Nanoparticles; Vaccines
PubMed: 36038102
DOI: 10.1016/j.fsi.2022.08.030 -
Frontiers in Pharmacology 2022N-Acetylcysteine (NAC) is used as an antidote in acetaminophen (APAP) overdose to prevent and mitigate drug-induced liver injury (DILI). Our objective was to...
N-Acetylcysteine (NAC) is used as an antidote in acetaminophen (APAP) overdose to prevent and mitigate drug-induced liver injury (DILI). Our objective was to systematically review evidence of the use of NAC as a therapeutic option for APAP overdose and APAP-related DILI in order to define the optimal treatment schedule and timing to start treatment. Bibliographic databases (PubMed, Web of Science, Embase, and MEDLINE) were searched for retrospective and prospective cohort studies, case series, and clinical trials. The prespecified primary outcomes were DILI-related mortality, hepatotoxicity, and adverse events (AEs). In total, 34 studies of NAC usage in APAP-related DILI cases with 19,580 patients were identified, of which 2,376 patients developed hepatotoxicities. The mortality rate across different studies ranged from 0 to 52%. Large variability of NAC regimens was found, i.e., intravenous (I.V.) (100-150 mg/kg) and oral (70-140 mg/kg), and length of treatment varied-12, 24, or 48 h for I.V. regimen and 72 h for oral administration. The timing of initiation of NAC treatment showed different results in terms of occurrence of hepatotoxicity and mortality; if started within 8 h and no more than 24 h from APAP overdose, either intravenously or orally, NAC administration was efficacious in terms of mortality. The most frequent AEs reported were anaphylactic reactions, followed by cutaneous AEs for the IV route and intestinal AEs for the oral one. NAC improves hepatotoxicity and reduces mortality. Timing of treatment, ranging from 8 to 24 h from APAP overdose, regardless of the regimen or route of administration, is important to prevent or minimize liver damage, particularly in children and in elderly and obese patients.
PubMed: 36034775
DOI: 10.3389/fphar.2022.828565