Cognitive impairment following clinical or recreational use of gamma-hydroxybutyric acid (GHB). A systematic review

2021 ◽  
Vol 19 ◽  
Author(s):  
Jan Van Amsterdam ◽  
Tibor M. Brunt ◽  
Filipa Raposo Pereira ◽  
Cleo L. Crunelle ◽  
Wim Van Den Brink
Keyword(s):  
Systematic Review ◽  
Cognitive Impairments ◽  
High Dose ◽  
General Anaesthetic ◽  
Hydroxybutyric Acid ◽  
Alcohol Relapse ◽  
Animal Data ◽  
High Doses ◽  
Recreational Use

Background: GHB (gamma-hydroxybutyric acid; sodium oxybate) is a general anaesthetic that is clinically used for the treatment of narcolepsy, cataplexy, alcohol withdrawal and alcohol relapse prevention. In addition, GHB is recreationally used. Most clinical and recreational users regard GHB as an innocent drug devoid of adverse effects, despite its high dependence potential and possible neurotoxic effects. At high doses, GHB may lead to a comatose state. This paper systematically reviews possible cognitive impairments due to clinical and recreational GHB use. Methods: PubMed and PsychINFO were searched for literature data about the acute and residual cognitive deficits following GHB use. This review is conducted using the PRISMA protocol. Results: A total of 43 reports covering human and animal data on GHB-induced cognitive impairments were eligible and reviewed. This systematic review found no indication for cognitive impairments after clinical GHB use. However, it supports the view that moderate GHB use may result in acute short-term cognitive impairments, whereas regular high-dose GHB use and/or multiple GHB-induced comas are probably neurotoxic resulting in long-term residual cognitive impairments. Conclusion: These results emphasize the need for awareness among clinicians and recreational users to minimize negative health consequences of recreational GHB use, particularly when high doses are used, and GHB-induced comas occur.

scholarly journals Association Between Glucocorticoids Treatment and Viral Clearance Delay in Patients with COVID-19: A Systematic Review and Meta-Analysis

2021 ◽  
Author(s):  
Jianbo Li ◽  
Xuelian Liao ◽  
Yue Zhou ◽  
Luping Wang ◽  
Hang Yang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Severity Of Illness ◽  
Viral Clearance ◽  
Cochrane Library ◽  
High Dose ◽  
Hazard Ratios ◽  
Subgroup Analyses ◽  
High Doses ◽  
Critical Ill

Abstract BackgroundEvidence of glucocorticoids on viral clearance delay of COVID-19 patients is not clear. MethodsIn this systematic review and meta-analysis, we searched studies on Medline, Embase, EBSCO, ScienceDirect, Web of Science, Cochrane Library, and ClinicalTrials.gov from 2002 to December 2, 2020. We mainly pooled the adjusted hazard ratios (HRs), mean difference (MD) or risk ratios (RRs) of viral clearance delay and did subgroup analyses by doses and the severity of illness.ResultsOne trial and 38 observational studies, with a total of 7119 patients, were identified. Glucocorticoids treatment was associated with delayed viral clearance in COVID-19 (Adjusted HR 1.71, 95% CI 1.51 to 1.94, I2=22%, PI 1.45 to 2.01), based on moderate-quality evidence. In subgroup analyses, risk of viral clearance delay was significantly higher among COVID-19 patients being mild or moderate ill (adjusted HR 1.94, 95% CI 1.39 to 2.70, I2=52%; MD 2.59, 95% CI 1.21 to 3.97, I2=24%), but not in those of being severe or critical ill (adjusted HR 1.85, 95% CI 1.05 to 3.26; MD 0.22, 95% CI -1.85 to 2.29, I2=56%); taking high doses (adjusted HR 1.49, 95% CI 1.03 to 2.15; unadjusted RR 1.47, 95% CI 1.12 to 1.94) rather taking low doses (adjusted HR 1.39, 95% CI 0.93 to 2.08; unadjusted RR 1.33, 95% CI 1.00 to 1.77) or pulse (unadjusted RR 1.85, 95% CI 0.66 to 5.19).ConclusionsGlucocorticoids treatment delayed viral clearance in COVID-19 patients of being mild or moderate ill or taking a high dose, rather in those of being severe or critical ill or taking low dose or pulse.

scholarly journals Association Between Glucocorticoids Treatment and Viral Clearance Delay in Patients with COVID-19: A Systematic Review and Meta-Analysis

2021 ◽  
Author(s):  
Jianbo Li ◽  
Xuelian Liao ◽  
Yue Zhou ◽  
Luping Wang ◽  
Hang Yang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Severity Of Illness ◽  
Viral Clearance ◽  
Cochrane Library ◽  
High Dose ◽  
Hazard Ratios ◽  
Subgroup Analyses ◽  
High Doses ◽  
Critical Ill

Abstract Background Evidence of glucocorticoids on viral clearance delay of COVID-19 patients is not clear. Methods In this systematic review and meta-analysis, we searched studies on Medline, Embase, EBSCO, ScienceDirect, Web of Science, Cochrane Library, and ClinicalTrials.gov from 2002 to December 2, 2020. We mainly pooled the adjusted hazard ratios (HRs), mean difference (MD) or risk ratios (RRs) of viral clearance delay and did subgroup analyses by doses and the severity of illness.Results One trial and 38 observational studies, with a total of 7119 patients, were identified. Glucocorticoids treatment was associated with delayed viral clearance in COVID-19 (Adjusted HR 1.71, 95% CI 1.51 to 1.94, I2=22%, PI 1.45 to 2.01), based on moderate-quality evidence. In subgroup analyses, risk of viral clearance delay was significantly higher among COVID-19 patients being mild or moderate ill (adjusted HR 1.94, 95% CI 1.39 to 2.70, I2=52%; MD 2.59, 95% CI 1.21 to 3.97, I2=24%), but not in those of being severe or critical ill (adjusted HR 1.85, 95% CI 1.05 to 3.26; MD 0.22, 95% CI -1.85 to 2.29, I2=56%); taking high doses (adjusted HR 1.49, 95% CI 1.03 to 2.15; unadjusted RR 1.47, 95% CI 1.12 to 1.94) rather taking low doses (adjusted HR 1.39, 95% CI 0.93 to 2.08; unadjusted RR 1.33, 95% CI 1.00 to 1.77) or pulse (unadjusted RR 1.85, 95% CI 0.66 to 5.19).Conclusions Glucocorticoids treatment delayed viral clearance in COVID-19 patients of being mild or moderate ill or taking a high dose, rather in those of being severe or critical ill or taking low dose or pulse.

scholarly journals Phosphorus Inactivation in Lake Sediments Using Calcite Materials and Controlled Resuspension—Mechanism and Efficiency

Minerals ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 223
Author(s):  
Agnieszka Bańkowska-Sobczak ◽  
Aurelia Blazejczyk ◽  
Elisabeth Eiche ◽  
Uwe Fischer ◽  
Zbigniew Popek
Keyword(s):  
Adsorption Capacity ◽  
Soluble Reactive Phosphorus ◽  
High Dose ◽  
Eutrophic Lakes ◽  
Precipitated Calcium Carbonate ◽  
Anoxic Conditions ◽  
P Fraction ◽  
Reactive Phosphorus ◽  
High Doses

The efficiency and mechanism of orthophosphate—soluble reactive phosphorus (SRP)—inactivation in eutrophic lakes using controlled resuspension and calcite application into the sediment were investigated in this study. Two calcite materials, industrially produced precipitated calcium carbonate (PCC) and natural ground limestone (GCC), were tested in short-term batch experiments and long-term sediment incubations under oxic and anoxic conditions. Maximum SRP adsorption capacity calculated using Langmuir model for PCC (3.11 mg PO43− g−1) was 6 times higher than of GCC (0.43 mg PO43− g−1), reflecting substantial difference in the surface area of calcite materials (12.36 and 1.72 m2 g−1, respectively). PCC applied into the sediment during controlled resuspension reduced SRP release by 95% (oxic) and 78% (anoxic incubation) at medium dose (0.75 kg m−2) and suppressed it completely at high dose (1.5 kg m−2) for at least 3 months, irrespectively of incubation conditions. The maximum achieved reduction of SRP release using GCC was also meaningful: 78% under oxic and 56% under anoxic conditions, but this required very high doses of this material (6 kg m−2). Mechanisms of SRP inactivation by calcites were: (1) adsorption of SRP during application into the resuspended sediment and (2) precipitation of calcium-phosphate compounds (Ca-PO4) during subsequent incubation, which was reflected in a substantial increase in the HCl-P fraction (phosphorus extractable in 0.5 M HCl) in sediments enriched with calcite, irrespectively of oxygen presence. However, anoxia strongly promoted the formation of this fraction: the rise of HCl-P was 2–6 times higher in anoxic than in oxic conditions, depending on the dose and form of calcite applied. The results showed that SRP inactivation using the controlled resuspension method is only successful if highly efficient reactive materials are used, due to large amount of SRP being released from sediment during resuspension. Thus, calcite materials exhibiting high adsorption capacity should be used in this lakes’ restoration technology to ensure fast and sufficient SRP inactivation. The rise in the HCl-P fraction in sediment suggests SRP inactivation through precipitation of relatively stable Ca-PO4 minerals, which makes calcite a suitable agent for sustainable, long term SRP inactivation. As anoxic conditions promoted formation of these compounds, calcite seems to be a promising SRP inactivation agent in highly reductive sediments.

Effects of long-term continuous GnRH administration on the pituitary–gonadal axis in Eld's deer stags (Cervus eldi thamin)

1995 ◽  
Vol 73 (9) ◽  
pp. 1609-1619 ◽  
Author(s):  
S. L. Monfort ◽  
J. L. Brown ◽  
T. C. Wood ◽  
M. Bush ◽  
L. R. Williamson ◽  
...  
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
High Dose ◽  
Fertile Period ◽  
Nonbreeding Season ◽  
Testosterone Secretion ◽  
High Doses ◽  
Seasonal Decline ◽  
Seasonally Breeding

Eld's deer stags (Cervus eldi thamin) (in groups of three) were continuously administered gonadotropin-releasing hormone (GnRH) in control, low, medium, or high doses (0, 20.1 ± 0.7, 83.3 ± 2.6, and 292.9 ± 4.9 ng∙kg−1∙d−1, respectively) via osmotic minipumps for ~80 d to investigate the potential for precociously reactivating the pituitary–testicular axis during the nonbreeding season. Secretory patterns of LH, FSH, and testosterone concentrations were qualitatively similar among treatments. However, in the low-dose group, basal LH and FSH concentrations were both increased (p < 0.05) and pituitary responsiveness to a superimposed GnRH challenge was augmented (p < 0.05) after 12 weeks of treatment compared with all other groups. Despite these endocrine changes, continuous low-dose GnRH administration was not effective for precociously inducing testicular activity in this seasonally breeding species. High-dose GnRH administration initially induced a transient increase in LH, FSH, and testosterone secretion and delayed, but did not prevent, the seasonal decline in spermatogenesis. After 6–12 weeks of high-dose GnRH administration, however, attenuated pituitary responsiveness appeared to delay the normal seasonal reactivation of the pituitary–gonadal axis. In conclusion, prolonged, continuous low-dose GnRH administration did not effectively translate into a precocious onset of testicular activity; therefore, this specific approach is unlikely to be useful for prolonging the fertile period in this seasonally breeding species.

scholarly journals Subtle Cognitive Impairments in Patients with Long-Term Cure of Cushing’s Disease

2010 ◽  
Vol 95 (6) ◽  
pp. 2699-2714 ◽  
Author(s):  
Jitske Tiemensma ◽  
Nieke E. Kokshoorn ◽  
Nienke R. Biermasz ◽  
Bart-Jan S. A. Keijser ◽  
Moniek J. E. Wassenaar ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Cognitive Functioning ◽  
Cushing’S Disease ◽  
Cognitive Impairments ◽  
Verbal Learning ◽  
Cushing's Disease ◽  
High Dose ◽  
Gender And Education ◽  
Irreversible Effects

Abstract Context and Objective: Active Cushing’s disease is associated with cognitive impairments. We hypothesized that previous hypercortisolism in patients with Cushing’s disease results in irreversible impairments in cognitive functioning. Therefore, our aim was to assess cognitive functioning after long-term cure of Cushing’s disease. Design: Cognitive assessment consisted of 11 tests, which evaluated global cognitive functioning, memory, and executive functioning. Patients and Control Subjects: We included 74 patients cured of Cushing’s disease and 74 controls matched for age, gender, and education. Furthermore, we included 54 patients previously treated for nonfunctioning pituitary macroadenomas (NFMA) and 54 controls matched for age, gender, and education. Results: Compared with NFMA patients, patients cured from Cushing’s disease had lower scores on the Mini Mental State Examination (P = 0.001), and on the memory quotient of the Wechsler Memory Scale (P = 0.050). Furthermore, patients cured from Cushing’s disease tended to recall fewer words on the imprinting (P = 0.013), immediate recall (P = 0.012), and delayed recall (P = 0.003) trials of the Verbal Learning Test of Rey. On the Rey Complex Figure Test, patients cured from Cushing’s disease had lower scores on both trials (P = 0.002 and P = 0.007) compared with NFMA patients. Patients cured from Cushing’s disease also made fewer correct substitutions on the Letter-Digit Substitution Test (P = 0.039) and came up with fewer correct patterns on the Figure Fluency Test (P = 0.003) compared with treated NFMA patients. Conclusions: Cognitive function, reflecting memory and executive functions, is impaired in patients despite long-term cure of Cushing’s disease. These observations indicate irreversible effects of previous hypercortisolism on cognitive function and, thus, on the central nervous system. These observations may also be of relevance for patients treated with high-dose exogenous glucocorticoids.

Fluconazole-Induced Symptomatic Phenytoin Toxicity

1994 ◽  
Vol 28 (2) ◽  
pp. 191-195 ◽  
Author(s):  
Richard M. Cadle ◽  
Golden J. Zenon ◽  
Maria C. Rodriguez-Barradas ◽  
Richard J. Hamill
Keyword(s):  
Continuous Monitoring ◽  
Case Reports ◽  
Review Literature ◽  
High Dose ◽  
Data Synthesis ◽  
High Doses ◽  
Phenytoin Toxicity ◽  
Cytochrome P 450 ◽  
Hepatic Cytochrome

OBJECTIVE: To report two cases of fluconazole-induced symptomatic phenytoin toxicity and review literature related to this interaction. DATA SOURCES: Case reports and review articles identified by a computerized (MEDLINE) and manual ( Index Medicus) search. DATA SYNTHESIS: Fluconazole is a broad-spectrum triazole antifungal agent primarily eliminated by renal mechanisms, although hepatic cytochrome P-450 inhibition and hepatotoxicity have been observed. We report two cases of fluconazole-induced symptomatic phenytoin toxicity. Both patients received high doses of the drug; one patient developed phenytoin toxicity only after long-term coadministration. Previously reported cases have occurred primarily with high-dose fluconazole and short-term coadministration. CONCLUSIONS: Fluconazole can increase phenytoin serum concentrations leading to toxicity. Constant and continuous monitoring of serum phenytoin concentrations with fluconazole doses as low as 200 mg/d is warranted.

scholarly journals Relationship between caffeine intake and infertility: a systematic review of controlled clinical studies

2020 ◽  
Author(s):  
Bu Fanlong ◽  
Xue Feng ◽  
Xiao-Ying Yang ◽  
Jun Ren ◽  
Hui-juan Cao
Keyword(s):  
Systematic Review ◽  
Cohort Study ◽  
Clinical Studies ◽  
Meta Analysis ◽  
Case Control ◽  
Average Score ◽  
Caffeine Intake ◽  
High Dose ◽  
Case Control Studies ◽  
High Doses

Abstract Background: Previous studies showed that high dose of caffeine intake may induce some specific human reproductive system diseases, even lead to infertility. This review is aimed to systematically review the evidence from all controlled clinical studies of caffeine intake for infertility.Methods: Relevant randomized/quasi-randomized controlled trials, non-randomized clinical studies, cohort studies, and case-control studies were included. Participants were either those without a history of infertility who are willing to have a baby (for prospective studies) or infertile patients with confirmed diagnosis (for retrospective studies). Caffeine or caffeine-containing beverage was observed as the exposure factor. The key outcome was the diagnosis of infertility.Results: Four studies (one cohort study and three case-control studies) involving 12912 participants were included. According Newcastle - Ottawa Scale (NOS), the average score of case-control studies was 6, and the cohort study achieved 9. Meta-analysis and subgroup analysis were conducted. The results showed that low (OR 0.95, 95%CI 0.78-1.16), medium (OR 1.14, 95%CI 0.69-1.86) and high doses (OR 1.86, 95%CI 0.28-12.22) of caffeine intake may not increase the risk of infertility. The GRADE method was used to assess the certainty of the evidence and the results showed that the quality of the three evidence bodies were all low.Conclusion: Our study provides low quality evidence that regardless of low, medium and high doses of caffeine intake do not appear increase the risk of infertility. But the conclusion should be treated with caution. Systematic review registration: PROSPERO CRD42015015714

scholarly journals Do Antioxidant Vitamins Prevent Exercise-Induced Muscle Damage? A Systematic Review

Antioxidants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 372 ◽  
Author(s):  
María Martinez-Ferran ◽  
Fabian Sanchis-Gomar ◽  
Carl J. Lavie ◽  
Giuseppe Lippi ◽  
Helios Pareja-Galeano
Keyword(s):  
Systematic Review ◽  
Creatine Kinase ◽  
Muscle Damage ◽  
Web Of Science ◽  
Exercise Session ◽  
Post Exercise ◽  
High Doses ◽  
Exercise Induced ◽  
Cell Signaling Pathways

Free radicals produced during exercise play a role in modulating cell signaling pathways. High doses of antioxidants may hamper adaptations to exercise training. However, their benefits are unclear. This review aims to examine whether vitamin C (VitC) and/or vitamin E (VitE) supplementation (SUP) prevents exercise-induced muscle damage. The PubMed, Web of Science, Medline, CINAHL, and SPORTDiscus databases were searched, and 21 articles were included. Four studies examined the effects of acute VitC SUP given pre-exercise: in one study, lower CK levels post-exercise was observed; in three, no difference was recorded. In one study, acute VitE SUP reduced CK activity 1 h post-exercise in conditions of hypoxia. In three studies, chronic VitE SUP did not reduce CK activity after an exercise session. Chronic VitE SUP did not reduce creatine kinase (CK) concentrations after three strength training sessions, but it was effective after 6 days of endurance training in another study. Chronic SUP with VitC + E reduced CK activity post-exercise in two studies, but there was no such effect in four studies. Finally, three studies described the effects of chronic VitC + E SUP and long-term exercise, reporting dissimilar results. To conclude, although there is some evidence of a protective effect of VitC and/or VitE against exercise-induced muscle damage, the available data are not conclusive.

Long-term treatment with finasteride induces apoptosis and pathological changes in female mice

2019 ◽  
Vol 38 (7) ◽  
pp. 762-774 ◽  
Author(s):  
AA Alkahtane ◽  
G Albasher ◽  
NK Al-Sultan ◽  
WS Alqahtani ◽  
S Alarifi ◽  
...  
Keyword(s):  
Serum Levels ◽  
Term Treatment ◽  
Androgenetic Alopecia ◽  
High Dose ◽  
Histopathological Analysis ◽  
Once Daily ◽  
Female Mice ◽  
Long Term Treatment ◽  
High Doses

Androgenetic alopecia is the most common type of alopecia, and it affects humans of both genders. Finasteride is a type II selective 5α-reductase inhibitor that is administered orally to treat androgenetic alopecia and benign prostatic hyperplasia in human males. However, its effect on the vital organs of females is unknown. This study was designed to investigate the effects of finasteride on the vital organs such as liver, kidney, and heart of female mice. To study the prospective effects of finasteride, female mice were orally administered two doses of finasteride (0.5 and 1.5 mg/kg) once daily for 35 days, and serum levels of various biochemical parameters and histopathology of various organs were examined. The results showed that serum levels of alkaline phosphatase were significantly increased by both high- and low-dose finasteride, whereas cholesterol was significantly increased by the high dose only. Creatine kinase was significantly increased by the high and low doses, whereas glucose was significantly decreased by both doses. Histopathological analysis and DNA damage assays showed that finasteride has adverse effects within both the short and the long periods in female mice. In addition, the proapoptotic genes Bax and caspase-3 were significantly increased by high dose finasteride, whereas the antiapoptotic gene Bcl-2 was significantly decreased by the low and high doses. In conclusion, finasteride is not currently approved for therapeutic use in females, and the findings in this study suggest caution in any future consideration of such use.

Immunomodulatory Effect of Ganoderma Lucidum Polysaccharides (GLP) on Long-Term Heavy-Load Exercising Mice

2012 ◽  
Vol 82 (6) ◽  
pp. 383-390 ◽  
Author(s):  
Yali Shi ◽  
Dehua Cai ◽  
Xiaojie Wang ◽  
Xinshen Liu
Keyword(s):  
Absolute Neutrophil Count ◽  
Neutrophil Count ◽  
Ganoderma Lucidum ◽  
Phagocytic Index ◽  
High Dose ◽  
Heavy Load ◽  
Ganoderma Lucidum Polysaccharides ◽  
High Doses ◽  
Serum Agglutination

Long-term heavy-load exercise can lead to a decrease in the organism’s immune response. In this study, we used 100 Kunming (KM) mice to investigate the immune-regulatory effects of Ganoderma lucidum polysaccharides (GLP) on long-term heavy-load exercising mice. Peripheral white blood cells (WBC), the absolute value of neutrophils (NEUT), the phagocytic function of macrophages, serum agglutination valence, and the number of plaque-forming cells (PFC) were evaluated 4 weeks after gavaging long-term heavy-load exercising mice with GLP. After exercise, the WBC count in peripheral blood, absolute neutrophil count, macrophage phagocytic index, serum agglutination valence, and the number of plaque-forming cells were significantly reduced in the mice not fed GLP. Both medium and high doses of GLP drastically increased peripheral WBC, absolute neutrophil count, macrophage phagocytic index, serum agglutination valence, and the number of plaque-forming cells in long-term heavy-load exercising mice. High doses of GLP increased peritoneal macrophage phagocytic rate considerably. With this study, we demonstrate that 4 weeks of heavy-load exercise can lead to exercise-induced immunosuppression in mice. A supplement of GLP fed to these mice improves both non-specific and specific immune responses among these mice. The effect for the high-dose GLP treatment is especially significant.

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