Glutathione

Authors:

Mickeal N Key

Participants:

older adults

Study Quality Assessment:

Narrative Review

Authors:

Koji Aoyama

Findings:

The review covers the transport, synthesis, catabolism, compartmentation, and biochemistry of glutathione in different brain cells, as well as its role in neurodegenerative and neurodevelopmental conditions. Healthy human brain glutathione concentration is stated to be approximately 1-2 mM, varying by brain region, with evidence of gender differences.

Participants:

Healthy humans (implied by 'Healthy human brain glutathione concentration')

Study Quality Assessment:

Review article (indicated by 'We review')

All Effects:

Authors:

Anu Asnaani, Stefan G Hofmann

Findings:

This review concludes that Cognitive–behavioral therapy (CBT) helps individuals eliminate avoidant and safety-seeking behaviors, thereby facilitating stress management to reduce stress-related disorders and enhance mental health. Results from several randomized controlled trials indicate CBT was effective in the short term for a variety of mental problems (e.g., anxiety, depression), physical conditions (e.g., chronic fatigue syndrome, irritable bowel syndrome), and behavioral problems (e.g., drug abuse, smoking). Online CBT or self-help CBT using mobile apps can also be effective but should be applied with care, considering cost-effectiveness and applicability.

Participants:

The review evaluated Cognitive Behavioral Therapy (CBT) effectiveness in stressful conditions among clinical and general populations. Clinical trials included in the review recruited samples from patient populations (e.g., for anxiety disorder, attention deficit hypersensitivity disorder, bulimia nervosa, depression, hypochondriasis, chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome, breast cancer) and non-patient populations (e.g., a working population).

Study Quality Assessment:

This is a review article. A literature search for studies conducted during 1987–2021 identified 345 articles; 154 (45%) were review articles (including 14 systemic reviews), and 53 (15%) were clinical trials (including 45 randomized controlled trials). The review notes that more follow-up observations are needed to assess the long-term effects of CBT. Funding for this review is stated: 'The study was supported in part by a Research Grant (Kiban C) from the Japanese Ministry of Education, Culture, Sports, Science and Technology.'

All Effects:

Authors:

Damian Kobylarz

Findings:

This critical review aims to provide comprehensive information on specific antidotes used in clinical toxicology, covering their recommended uses, potential risks, mechanisms of action, and emerging applications. It emphasizes that while supportive therapies are common in poisoning cases, appropriate antidote administration can be life-saving or reduce toxicity severity. The review details biochemical characteristics and dosage recommendations for selected antidotes, and also discusses alternative therapeutic uses, such as N-acetylcysteine for COVID-19, and highlights the potential for developing new antidotes, including supramolecular ones.

Participants:

The review article discusses antidotes used in various human populations (e.g., "patients who have been poisoned or overdosed", "patients with cardiovascular disease", "patients waiting for a kidney transplant", "elderly people", "paediatric and adult patients", "patients with mild to moderate acute lung injury") and animal models (e.g., "dogs", "rats", "mice") as described in the literature it reviews.

Dosage:

The review provides detailed dosage recommendations for numerous antidotes, including: Lipid emulsion: '1.5 mL/kg (lean body weight) intravenously for 1 min', bolus repeatable, upper limit '10–12 mL/kg... in the first 30 min'. Pralidoxime (2-PAM): 'intravenously at a dose of 1–2 g (30 mg/kg bw) for 15–30 min, repeated 60 min later'. Obidoxime: 'Intravenous obidoxime in a dose of 250 mg'. Succimer: 'oral dose for moderate adults is 100 mg three times a day'. Ethanol: 'maintain an ethanol level between 1 and 1.5 g/L'. Fomepizole: 'loading dose is 15 mg/kg bw in a slow infusion (30 min)', then '15 mg/kg every 12 h'. Atropine: 'intravenous or intramuscular administration for adults at 1–2 mg, repeated every 5–60 min'. Calcium chloride (beta-blocker/calcium channel blocker overdose): '1000 mg is administered intravenously bolus'. Dantrolene (malignant hyperthermia): '2.5 mg/kg... intravenously', up to '10 mg/kg' cumulative; (chronic muscle spasticity): 'initial dose... 25 mg orally every day', max '400 mg per day'. N-acetylcysteine (COVID-19 prevention): 'A 600 mg dose twice a day'; (paracetamol poisoning): administration within 4-8h, not later than 14h, intravenously. Hydroxocobalamin (cyanide poisoning): 'For adults, the maximum administered dose is 10 g'. Insulin (HIET for CCB overdose): '1 unit/kg intravenously'. L-Carnitine (valproic acid overdose): 'A single intravenous loading dose of 100 mg/kg', then 'maximum 3 g per dose every 8 h'. Methylene blue (methemoglobinemia): '1 mg/kg bw of a 1% solution', max '100 mg'. Octreotide (sulfonylurea poisoning): '50–100 μg every 6–12 h'. Physostigmine (anticholinergic toxicity): '1–2 mg i.v. over 5 min', with possible additional doses. Prussian blue (thallium poisoning): '20 g/day'; (caesium poisoning): '3 g/day'. Pyridoxine (INH toxicity, unknown INH dose): '5 g of pyridoxine is administered intravenously to adult patients'. Starch (iodine poisoning): 'A 15 g dose of starch solution dissolved in 500 mL of water'. Vitamin K1 (rodenticide poisoning): 'Dosage for adults is 10–50 mg of vitamin K1 2–4 times a day'.

Study Quality Assessment:

The article is a "Critical Review" published in "Toxics. 2023 Aug 23;11(9):723". Its stated methodology is: "In this review, we reviewed the literature on selected antidotes used in the treatment of poisonings. We also characterised the antidotes (bio)chemically. We described the cases in which they are used together with the dosage recommendations. We also analysed the mechanisms of action." Funding is acknowledged: "This article was written as part of the implementation of the project of the Polish Ministry of Education and Science, “Toxicovigilance, poisoning prevention, and first aid in poisoning with xenobiotics of current clinical importance in Poland”, grant number SKN/SP/570184/2023." The article is an "open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)". An NLM disclaimer is present: "Inclusion in an NLM database does not imply endorsement of, or agreement with, the contents by NLM or the National Institutes of Health."

All Effects:

Findings:

Patients with MCI had significantly elevated ratios of glutathione in the anterior and posterior cingulate compared to controls. Higher anterior cingulate glutathione related to decrements in executive functions, while elevated posterior cingulate glutathione was associated with poorer memory consolidation. This suggests MCI is associated with increased cingulate glutathione, possibly an early compensatory or neuroprotective response.

Participants:

Fifty-four patients with MCI and 41 healthy control subjects.

Study Quality Assessment:

Methods: proton magnetic resonance spectroscopy, medical, psychiatric, and neuropsychological assessments. Concentration of glutathione measured in anterior and posterior cingulate; ratios calculated relative to creatine. Neuropsychological performance assessed (processing speed, learning, memory, executive functions). Sample size: N=54 MCI patients, N=41 healthy controls. Acknowledges need for longitudinal studies.

All Effects: