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Dementia & Neuropsychologia 2024The disability of cells to react to insulin, causing glucose intolerance and hyperglycemia, is referred to as insulin resistance. This clinical condition, which has been... (Review)
Review
UNLABELLED
The disability of cells to react to insulin, causing glucose intolerance and hyperglycemia, is referred to as insulin resistance. This clinical condition, which has been well-researched in organs such as adipose tissue, muscle, and liver, has been linked to neurodegenerative diseases like Alzheimer's disease (AD) when it occurs in the brain.
OBJECTIVE
The authors aimed to gather data from the current literature on brain insulin resistance (BIR) and its likely repercussions on neurodegenerative disorders, more specifically AD, through a systematic review.
METHODS
A comprehensive search was conducted in multiple medical databases, including the Cochrane Central Register of Controlled Trials, EMBASE, Medical Literature Analysis and Retrieval System Online (Medline), and PubMed, employing the descriptors: "insulin resistance", "brain insulin resistance", "Alzheimer's disease", "neurodegeneration", and "cognition". The authors focused their search on English-language studies published between 2000 and 2023 that investigated the influence of BIR on neurodegenerative disorders or offered insights into BIR's underlying mechanisms. Seventeen studies that met the inclusion criteria were selected.
RESULTS
The results indicate that BIR is a phenomenon observed in a variety of neurodegenerative disorders, including AD. Studies suggest that impaired glucose utilization and uptake, reduced adenosine triphosphate (ATP) production, and synaptic plasticity changes caused by BIR are linked to cognitive problems. However, conflicting results were observed regarding the association between AD and BIR, with some studies suggesting no association.
CONCLUSION
Based on the evaluated studies, it can be concluded that the association between AD and BIR remains inconclusive, and additional research is needed to elucidate this relationship.
PubMed: 38425702
DOI: 10.1590/1980-5764-DN-2023-0032 -
Frontiers in Neuroscience 2021Cerebral energy supply is determined by the energy content of the blood. Accordingly, the brain is undersupplied during hypoglycaemia. Whether or not there is an...
Cerebral energy supply is determined by the energy content of the blood. Accordingly, the brain is undersupplied during hypoglycaemia. Whether or not there is an additional cerebral energy demand that depends upon the energy content of the brain is considered differently in two opposing theoretical approaches. The Selfish-Brain theory postulates that the brain actively demands energy from the body when needed, while long-held theories, the gluco-lipostatic theory and its variants, deny such active brain involvement and view the brain as purely passively supplied. Here we put the competing theories to the test. We conducted a systematic review of a condition in which the rival theories make opposite predictions, i.e., experimental T1DM. The Selfish-Brain theory predicts that induction of experimental type 1 diabetes causes minor mass (energy) changes in the brain as opposed to major glucose changes in the blood. This prediction becomes our hypothesis to be tested here. A total of 608 works were screened by title and abstract, and 64 were analysed in full text. According to strict selection criteria defined in our PROSPERO preannouncement and complying with PRISMA guidelines, 18 studies met all inclusion criteria. Thirteen studies provided sufficient data to test our hypothesis. The 13 evaluable studies (15 experiments) showed that the diabetic groups had blood glucose concentrations that differed from controls by +294 ± 96% (mean ± standard deviation) and brain mass (energy) that differed from controls by -4 ± 13%, such that blood changes were an order of magnitude greater than brain changes ( = 11.5, df = 14, < 0.001). This finding confirms not only our hypothesis but also the prediction of the Selfish-Brain theory, while the predictions of the gluco-lipostatic theory and its variants were violated. The current paper completes a three-part series of systematic reviews, the two previous papers deal with a distal and a proximal bottleneck in the cerebral brain supply, i.e., caloric restriction and cerebral artery occlusion. All three papers demonstrate that accurate predictions are only possible if one regards the brain as an organ that regulates its energy concentrations independently and occupies a primary position in a hierarchically organised energy metabolism. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=156816, PROSPERO, identifier: CRD42020156816.
PubMed: 34803585
DOI: 10.3389/fnins.2021.740502 -
Cureus Oct 2022Coronary artery disease (CAD) is one of the leading causes of death worldwide. Atherosclerosis begins in childhood as fatty streaks, progresses with age, and lifestyle... (Review)
Review
Coronary artery disease (CAD) is one of the leading causes of death worldwide. Atherosclerosis begins in childhood as fatty streaks, progresses with age, and lifestyle influences the progression of atherosclerotic plaque. Over time, with significant narrowing of the blood vessels, blood flow into the coronary arteries is compromised, resulting in various symptoms of coronary heart disease. Many drugs are used in clinical practice to prevent atherosclerotic cardiovascular events in patients with CAD. This review aims to investigate the efficacy and safety of a non-statin novel lipid-lowering drug, bempedoic acid (BDA), an adenosine triphosphate (ATP) citrate lyase inhibitor, in lowering serum low-density lipoprotein cholesterol (LDL-C) levels among patients with CAD. BDA is a new drug that recently got approval for clinical use. Following its discovery, BDA has been researched in order to investigate its role in the treatment of hypercholesterolemia. A search for studies was conducted using databases such as PubMed, PMC, ScienceDirect, and Google Scholar up until April 30, 2022. This systematic review has followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 11 studies were finalized to explore the role of BDA alone or as an adjunct in lowering serum LDL-C levels in high-risk patients under maximally tolerated statins, statin-intolerant groups, or treatment with other lipid-lowering drugs. These studies are three randomized controlled trials (RCTs), one pre-proof RCT, two systematic reviews and meta-analyses, and five narrative review articles. This review included 8465 participants from recently conducted RCTs and systematic reviews. Another 14014 participants, enrolled for the Cholesterol Lowering via Bempedoic Acid, an Adenosine Triphosphate-Citrate Lyase-Inhibiting Regimen (CLEAR) Outcomes clinical trial, were also included. BDA in combination with ezetimibe showed good evidence of LDL-C lowering effect. Patients on maximally tolerated statin failing to achieve desired LDL-C when treated in combination with BDA showed a significant decrement in serum LDL-C levels, high sensitivity C-reactive protein (HsCRP), and triglyceride. BDA use showed no adverse side effects. The most common side effect seen in several trials was the rise in serum uric acid level. When treating patients with BDA, baseline uric acid levels should be obtained and regular monitoring of uric acid should be done. The CLEAR Outcomes trial, scheduled to be completed by December 2022, will provide further information on BDA. BDA appears to be a promising alternative to currently available secondary lipid-lowering agents.
PubMed: 36348882
DOI: 10.7759/cureus.29891 -
Biological Reviews of the Cambridge... Aug 2022In many animal species, males may exhibit one of several discrete, alternative ways of obtaining fertilisations, known as alternative reproductive tactics (ARTs). Males... (Meta-Analysis)
Meta-Analysis
In many animal species, males may exhibit one of several discrete, alternative ways of obtaining fertilisations, known as alternative reproductive tactics (ARTs). Males exhibiting ARTs typically differ in the extent to which they invest in traits that improve their mating success, or the extent to which they face sperm competition. This has led to the widespread prediction that males exhibiting ARTs associated with a high sperm competition risk, or lower investment into traits that improve their competitiveness before mating, should invest more heavily into traits that improve their competitiveness after mating, such as large ejaculates and high-quality sperm. However, despite many studies investigating this question since the 1990s, evidence for differences in sperm and ejaculate investment between male ARTs is mixed, and there has been no quantitative summary of this field. Following a systematic review of the literature, we performed a meta-analysis examining how testes size, sperm number and sperm traits differ between males exhibiting ARTs that face either a high or low sperm competition risk, or high or low investment in traits that increase mating success. We obtained data from 92 studies and 67 species from across the animal kingdom. Our analyses showed that male fish exhibiting ARTs facing a high sperm competition risk had significantly larger testes (after controlling for body size) than those exhibiting tactics facing a low sperm competition risk. However, this effect appears to be due to the inappropriate use of the gonadosomatic index as a body-size corrected measure of testes investment, which overestimates the difference in testes investment between male tactics in most cases. We found no significant difference in sperm number between males exhibiting different ARTs, regardless of whether sperm were measured from the male sperm stores or following ejaculation. We also found no significant difference in sperm traits between males exhibiting different ARTs, with the exception of sperm adenosine triphosphate (ATP) content in fish. Finally, the difference in post-mating investment between male ARTs was not influenced by the extent to which tactics were flexible, or by the frequency of sneakers in the population. Overall, our results suggest that, despite clear theoretical predictions, there is little evidence that male ARTs differ substantially in investment into sperm and ejaculates across species. The incongruence between theoretical and empirical results could be explained if (i) theoretical models fail to account for differences in overall resource levels between males exhibiting different ARTs or fundamental trade-offs between investment into different ejaculate and sperm traits, and (ii) studies often use sperm or ejaculate traits that do not reflect overall post-mating investment accurately or affect fertilisation success.
Topics: Animals; Body Size; Ejaculation; Fishes; Male; Reproduction; Semen; Sexual Behavior, Animal; Spermatozoa
PubMed: 35229450
DOI: 10.1111/brv.12846 -
Sports (Basel, Switzerland) Mar 2024Adenosine triphosphate (ATP) is an energy and signaling molecule. It is synthesized endogenously and can be taken as an oral supplement. This review aimed to identify... (Review)
Review
Adenosine triphosphate (ATP) is an energy and signaling molecule. It is synthesized endogenously and can be taken as an oral supplement. This review aimed to identify the effects of oral ATP supplementation on anaerobic exercise in healthy resistance-trained adults. A systematic review and meta-analysis were performed based on the Preferred Reporting Items of Systematic Reviews and Meta-Analysis (PRISMA) criteria. The inclusion criteria were articles published from 2000 to 2022, with anaerobic variables (maximal strength, maximum repetitions, and maximum anaerobic power) measurable in healthy adults with experience in resistance training, only randomized placebo-controlled clinical trials (RCTs), and with the acute (a single dose 30 min to 24 h before the tests) and/or chronic (>1 day) oral supplementation of ATP. A total of five RCTs with 121 adult men were included. The oral ATP supplementation achieved significantly greater gains in maximal strength compared with the placebo (PL) (MD = 8.13 kg, 95%CI [3.36-12.90], < 0.001). Still, no differences were observed in the maximum number of repetitions or the maximum anaerobic power. Furthermore, 400 mg of ATP showed improvement in anaerobic exercise regardless of the duration of the supplementation protocol. In conclusion, supplementation with 400 mg of ATP doses can improve maximal muscle strength in resistance-trained men.
PubMed: 38535745
DOI: 10.3390/sports12030082 -
Genes May 2024This systematic review and meta-analysis aimed to verify the association between the genetic variants of adenosine triphosphate (ATP)-binding cassette subfamily B member... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis aimed to verify the association between the genetic variants of adenosine triphosphate (ATP)-binding cassette subfamily B member 1 () and ATP-binding cassette subfamily G member 2 () genes and the presence and severity of gefitinib-associated adverse reactions. We systematically searched PubMed, Virtual Health Library/Bireme, Scopus, Embase, and Web of Science databases for relevant studies published up to February 2024. In total, five studies were included in the review. Additionally, eight genetic variants related to (rs1045642, rs1128503, rs2032582, and rs1025836) and (rs2231142, rs2231137, rs2622604, and 15622C>T) genes were analyzed. Meta-analysis showed a significant association between the gene rs1045642 TT genotype and presence of diarrhea (OR = 5.41, 95% CI: 1.38-21.14, I = 0%), the gene rs1128503 TT genotype and CT + TT group and the presence of skin rash (OR = 4.37, 95% CI: 1.51-12.61, I = 0% and OR = 6.99, 95%CI: 1.61-30.30, I= 0%, respectively), and the gene rs2231142 CC genotype and presence of diarrhea (OR = 3.87, 95% CI: 1.53-9.84, I = 39%). No or genes were positively associated with the severity of adverse reactions associated with gefitinib. In conclusion, this study showed that and variants are likely to exhibit clinical implications in predicting the presence of adverse reactions to gefitinib.
Topics: ATP Binding Cassette Transporter, Subfamily G, Member 2; Humans; ATP Binding Cassette Transporter, Subfamily B; Gefitinib; Neoplasm Proteins; Polymorphism, Single Nucleotide; Antineoplastic Agents; Drug-Related Side Effects and Adverse Reactions; Genotype
PubMed: 38790220
DOI: 10.3390/genes15050591 -
Journal of Obesity 2024Type 2 diabetes mellitus and metabolic syndrome represent two closely intertwined public health challenges that have reached alarming epidemic proportions in low- and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Type 2 diabetes mellitus and metabolic syndrome represent two closely intertwined public health challenges that have reached alarming epidemic proportions in low- and middle-income countries, particularly in sub-Saharan Africa. Therefore, the current study aimed to determine the weighted pooled prevalence of metabolic syndrome and its components among individuals with type 2 diabetes mellitus in sub-Saharan Africa as defined by the 2004 National Cholesterol Education Program-Adult Treatment Panel (NCEP-ATP III 2004) and/or the International Diabetes Federation (IDF) criteria.
METHODS
A systematic search was conducted to retrieve studies published in the English language on the prevalence of metabolic syndrome among type 2 diabetic individuals in sub-Saharan Africa. Searches were carried out in PubMed, Embase, Scopus, Google Scholar, African Index Medicus, and African Journal Online from their inception until July 31, 2023. A random-effects model was employed to estimate the weighted pooled prevalence of metabolic syndrome in sub-Saharan Africa. Evidence of between-study variance attributed to heterogeneity was assessed using Cochran's Q statistic and the I2 statistic. The Joanna Briggs Institute quality appraisal criteria were used to evaluate the methodological quality of the included studies. The summary estimates were presented with forest plots and tables. Publication bias was checked with the funnel plot and Egger's regression test.
RESULTS
Overall, 1421 articles were identified and evaluated using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, and 30 studies that met the inclusion criteria were included in the final analysis. The weighted pooled prevalence of metabolic syndrome among individuals with type 2 diabetes mellitus in sub-Saharan Africa was 63.1% (95% CI: 57.9-68.1) when using the NCEP-ATP III 2004 criteria and 60.8% (95% CI: 50.7-70.0) when using the IDF criteria. Subgroup analysis, using NCEP-ATP III 2004 and IDF criteria, revealed higher weighted pooled prevalence among females: 73.5% (95% CI: 67.4-79.5), 71.6% (95% CI: 60.2-82.9), compared to males: 50.5% (95% CI: 43.8-57.2), 44.5% (95% CI: 34.2-54.8), respectively. Central obesity was the most prevalent component of metabolic syndrome, with a pooled prevalence of 55.9% and 61.6% using NCEP-ATP III 2004 and IDF criteria, respectively. There was no statistical evidence of publication bias in both the NCEP-ATP III 2004 and IDF pooled estimates.
CONCLUSIONS
The findings underscore the alarming prevalence of metabolic syndrome among individuals with type 2 diabetes mellitus in sub-Saharan Africa. Therefore, it is essential to promote lifestyle modifications, such as regular exercise and balanced diets, prioritize routine obesity screenings, and implement early interventions and robust public health measures to mitigate the risks associated with central obesity.
Topics: Male; Adult; Female; Humans; Metabolic Syndrome; Diabetes Mellitus, Type 2; Risk Factors; Obesity, Abdominal; Prevalence; Obesity; Africa South of the Sahara; Adenosine Triphosphate
PubMed: 38410415
DOI: 10.1155/2024/1240457 -
Journal of Food Protection Dec 2022Adherence to proper environmental cleaning practices is critical in food establishments. To validate cleanliness, cleaning practices should be routinely monitored,... (Meta-Analysis)
Meta-Analysis
Relationship between ATP Bioluminescence Measurements and Microbial Assessments in Studies Conducted in Food Establishments: A Systematic Literature Review and Meta-Analysis.
ABSTRACT
Adherence to proper environmental cleaning practices is critical in food establishments. To validate cleanliness, cleaning practices should be routinely monitored, preferably by a rapid, reliable, and cost-effective method. The aim of this study was to determine whether a correlation exists between ATP bioluminescence measurements and selected microbial assessments in studies conducted in food establishments. A systematic literature review and meta-analysis was conducted using the principles of preferred reporting items for systematic reviews and meta-analyses. Twelve online databases and search engines were selected for the review. Peer-reviewed articles published in English between January 2000 and July 2020 were included in the search. From a total of 19 eligible studies, 3 that included Pearson correlation coefficients (r) between ATP bioluminescence measurements and microbial assessments were used for the meta-analysis calculations. Only the fixed-effect model produced a strong correlation because one value dominated the estimates: r = 0.9339 (0.9278, 0.9399). In contrast, both the random effects model, 0.2978 (0.24, 0.3471), and the mixed effects model, r = 0.3162 (-0.0387, 0.6711), indicated a weak relationship between ATP bioluminescence and microbial assessments, with no evidence of a strong correlation. The meta-analysis results indicated no sufficient evidence of a strong correlation between ATP bioluminescence measurements and microbial assessments when applied within food establishments. This lack of evidence for a strong correlation between the results of these two monitoring tools suggests that food establishments cannot depend on only one method. Yet, with immediate feedback and quantification of organic soiling, ATP bioluminescence could be an effective monitoring tool to use in food establishments.
Topics: Colony Count, Microbial; Adenosine Triphosphate; Luminescent Measurements; Food
PubMed: 36173898
DOI: 10.4315/JFP-22-187 -
International Journal of Molecular... Feb 2023Adequate imatinib plasma levels are necessary to guarantee an efficacious and safe treatment in gastrointestinal stromal tumor (GIST) and chronic myeloid leukemia (CML)... (Meta-Analysis)
Meta-Analysis
Adequate imatinib plasma levels are necessary to guarantee an efficacious and safe treatment in gastrointestinal stromal tumor (GIST) and chronic myeloid leukemia (CML) patients. Imatinib is a substrate of the drug transporters ATP-binding cassette subfamily B member 1 (ABCB1) and ATP-binding cassette subfamily G member 2 (ABCG2) that can affect its plasma concentration. In the present study, the association between three genetic polymorphisms in (rs1045642, rs2032582, rs1128503) and one in (rs2231142) and the imatinib plasma trough concentration (C) was investigated in 33 GIST patients enrolled in a prospective clinical trial. The results of the study were meta-analyzed with those of other seven studies (including a total of 649 patients) selected from the literature through a systematic review process. The c.421C>A genotype demonstrated, in our cohort of patients, a borderline association with imatinib plasma trough levels that became significant in the meta-analysis. Specifically, homozygous carriers of the c.421 A allele showed higher imatinib plasma C with respect to the CC/CA carriers (C, 1463.2 ng/mL AA, vs. 1196.6 ng/mL CC + AC, = 0.04) in 293 patients eligible for the evaluation of this polymorphism in the meta-analysis. The results remained significant under the additive model. No significant association could be described between polymorphisms and imatinib C, neither in our cohort nor in the meta-analysis. In conclusion, our results and the available literature studies sustain an association between c.421C>A and imatinib plasma C in GIST and CML patients.
Topics: Humans; Adenosine Triphosphate; Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily G, Member 2; Gastrointestinal Stromal Tumors; Genotype; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Neoplasm Proteins; Polymorphism, Single Nucleotide; Prospective Studies
PubMed: 36834713
DOI: 10.3390/ijms24043303 -
Pediatric Rheumatology Online Journal 2014Methotrexate (MTX) is the cornerstone disease-modifying anti-rheumatic drug in juvenile idiopathic arthritis (JIA). In JIA, it is important to start effective treatment... (Review)
Review
BACKGROUND
Methotrexate (MTX) is the cornerstone disease-modifying anti-rheumatic drug in juvenile idiopathic arthritis (JIA). In JIA, it is important to start effective treatment early to avoid long-term sequelae, such as joint damage. To accomplish this goal, it is crucial to know beforehand who is going to respond well to MTX. In addition, MTX adverse effects such as MTX intolerance occur frequently, potentially hindering its efficacy. To avoid inefficacy of an otherwise effective drug, the physician should be timely aware of these adverse events. Consequently, to optimise treatment of JIA patients with MTX, predictors for efficacy and adverse events should be used in daily clinical practice. The aim of this study was to summarise the existing knowledge about such predictors.
METHODS
A systematic literature search was performed in PubMed, Embase and The Cochrane Library, and 1,331 articles were identified. These were selected based on their relevance to the topic and critically appraised according to pre-defined criteria. Predictors for MTX efficacy and adverse events were extracted from the literature and tabulated.
RESULTS
Twenty articles were selected. The overall quality of the studies was good. For MTX efficacy, candidate predictors were antinuclear antibody positivity, the childhood health assessment questionnaire score, the myeloid-related protein 8/14 level, long-chain MTX polyglutamates, bilateral wrist involvement and some single nucleotide polymorphisms (SNPs) in the adenosine triphosphate binding cassette and solute carrier transporter gene families. For MTX adverse events, potential predictors were alanine aminotransferase and thrombocyte level and two SNPs in the γ-glutamyl hydrolase and methylenetetrahydrofolate reductase genes. However, validation of most predictors in independent cohorts was still lacking.
CONCLUSIONS
Interesting candidate predictors were found, especially for MTX efficacy. However, most of these were not validated. This should be the goal of future efforts. A clinically relevant way to validate the predictors is by means of creating a clinical prediction model.
Topics: ATP-Binding Cassette Transporters; Adolescent; Antibodies, Antinuclear; Antirheumatic Agents; Arthritis, Juvenile; Biomarkers; Child; Child, Preschool; Humans; Methotrexate; Polyglutamic Acid; Polymorphism, Single Nucleotide; Predictive Value of Tests; Treatment Outcome
PubMed: 25525416
DOI: 10.1186/1546-0096-12-51