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Clinical Biochemistry Sep 2018Platelet-activating factor (PAF) is a glycerylether lipid and one of the most potent endogenous mediators of inflammation. Through its binding to a well-characterized... (Review)
Review
Platelet-activating factor (PAF) is a glycerylether lipid and one of the most potent endogenous mediators of inflammation. Through its binding to a well-characterized receptor it initiates a plethora of cellular pro-inflammatory actions participating by this way to the pathology of most chronic diseases, including cardiovascular and renal diseases, CNS decline and cancer. Among the variety of prudent dietary patterns, Mediterranean Diet (MD) is the dietary pattern with the strongest evidence for its ability to prevent the same chronic diseases. In addition, micronutrients and extracts from several components and characteristic food of the MD can favorably modulate PAF's actions and metabolism either directly or indirectly. However, the role of this traditional diet on PAF metabolism and actions has rarely been studied before. This systematic review summarizes, presents and discusses the outcomes of epidemiologic and intervention studies in humans, investigating the relationships between PAF status and MD. Seventeen full-text articles trying to interlink the components of MD and PAF are found and presented. The results are inconsistent due to the variability of the measured indices and methodology followed. However, preliminary results indicate that the characteristic "healthy" components of the MD, especially, cereals, legumes, vegetables, fish and wine can favorably modulate the pro-inflammatory actions of PAF and regulate its metabolism. Larger, well-controlled studies are necessary to elucidate whether the attenuation of PAF actions can mediate the preventive properties of MD against chronic diseases.
Topics: Cardiovascular Diseases; Chronic Disease; Diet, Mediterranean; Humans; Inflammation Mediators; Platelet Activating Factor
PubMed: 30142319
DOI: 10.1016/j.clinbiochem.2018.08.004 -
The American Journal of Psychiatry Jul 2018Genes, infection, malnutrition, and other factors affecting fetal brain development are a major component of risk for a child's emotional development and later mental...
Genes, infection, malnutrition, and other factors affecting fetal brain development are a major component of risk for a child's emotional development and later mental illnesses, including schizophrenia, bipolar disorder, and autism. Prenatal interventions to ameliorate that risk have yet to be established for clinical use. A systematic review of prenatal nutrients and childhood emotional development and later mental illness was performed. Randomized trials of folic acid, phosphatidylcholine, and omega-3 fatty acid supplements assess effects of doses beyond those adequate to remedy deficiencies to promote normal fetal development despite genetic and environmental risks. Folic acid to prevent neural tube defects is an example. Vitamins A and D are currently recommended at maximum levels, but women's incomplete compliance permits observational studies of their effects. Folic acid and phosphatidylcholine supplements have shown evidence for improving childhood emotional development associated with later mental illnesses. Vitamins A and D decreased the risk for schizophrenia and autism in retrospective observations. Omega-3 fatty acid supplementation during early pregnancy increased the risk for schizophrenia and increased symptoms of attention deficit hyperactivity disorder, but in later pregnancy it decreased childhood wheezing and premature birth. Studies are complicated by the length of time between birth and the emergence of mental illnesses like schizophrenia, compared with anomalies like facial clefts identified at birth. As part of comprehensive maternal and fetal care, prenatal nutrient interventions should be further considered as uniquely effective first steps in decreasing risk for future psychiatric and other illnesses in newborn children. [AJP at 175: Remembering Our Past As We Envision Our Future July 1959: Longitudinal Observations of Biological Deviations in a Schizophrenic Infant Barbara Fish described the course of an infant born with fluctuating motor problems who developed schizophrenia. (Am J Psychiatry 1959; 116:25-31 )].
Topics: Dietary Supplements; Fatty Acids, Omega-3; Female; Folic Acid; Humans; Mental Disorders; Micronutrients; Phosphatidylcholines; Pregnancy; Prenatal Care; Primary Prevention
PubMed: 29558816
DOI: 10.1176/appi.ajp.2018.17070836 -
Advances in Medical Sciences Sep 2018Anaphylaxis is defined as severe, life-threatening, systemic or general, immediate reaction of hypersensitivity, with repeatable symptoms caused by the dose of stimulus...
Anaphylaxis is defined as severe, life-threatening, systemic or general, immediate reaction of hypersensitivity, with repeatable symptoms caused by the dose of stimulus which is well tolerated by healthy persons. The proper diagnosis, immediate treatment and differential diagnosis are crucial for saving patient's life. However, anaphylaxis is relatively frequently misdiagnosed or confused with other clinical entities. Thus, there is a continuous need for identifying detectable markers improving the proper diagnosis of anaphylaxis. Here we presented currently known markers of anaphylaxis and discussed in more detail the most clinically valuable ones: tryptase, platelet activacting factor (PAF), PAF-acethylhydrolase, histamine and its metabolites.
Topics: Anaphylaxis; Biomarkers; Histamine; Humans; Platelet Activating Factor; Tryptases
PubMed: 29486376
DOI: 10.1016/j.advms.2017.12.003 -
International Journal of Molecular... Nov 2017The multifunctional sphingosine-1-phosphate (S1P) is a lipid signaling molecule and central regulator in the development of several cancer types. In recent years,... (Review)
Review
The multifunctional sphingosine-1-phosphate (S1P) is a lipid signaling molecule and central regulator in the development of several cancer types. In recent years, intriguing information has become available regarding the role of S1P in the progression of Glioblastoma multiforme (GBM), the most aggressive and common brain tumor in adults. S1P modulates numerous cellular processes in GBM, such as oncogenesis, proliferation and survival, invasion, migration, metastasis and stem cell behavior. These processes are regulated via a family of five G-protein-coupled S1P receptors (S1PR1-5) and may involve mainly unknown intracellular targets. Distinct expression patterns and multiple intracellular signaling pathways of each S1PR subtype enable S1P to exert its pleiotropic cellular actions. Several studies have demonstrated alterations in S1P levels, the involvement of S1PRs and S1P metabolizing enzymes in GBM pathophysiology. While the tumorigenic actions of S1P involve the activation of several kinases and transcription factors, the specific G-protein (Gi, Gq, and G12/13)-coupled signaling pathways and downstream mediated effects in GBM remain to be elucidated in detail. This review summarizes the recent findings concerning the role of S1P and its receptors in GBM. We further highlight the current insights into the signaling pathways considered fundamental for regulating the cellular processes in GMB and ultimately patient prognosis.
Topics: Adult; Brain Neoplasms; Cell Movement; Disease Progression; GTP-Binding Proteins; Glioblastoma; Humans; Lysophospholipids; Neoplasm Invasiveness; Neoplasm Metastasis; Prognosis; Receptors, Lysosphingolipid; Sphingosine
PubMed: 29149079
DOI: 10.3390/ijms18112448 -
Journal of Reproductive Immunology Sep 2017Antiphospholipid syndrome (APS) is an autoimmune condition that is associated with thrombosis and morbidity in pregnancy. The exact mechanisms by which these... (Meta-Analysis)
Meta-Analysis Review
Antiphospholipid syndrome (APS) is an autoimmune condition that is associated with thrombosis and morbidity in pregnancy. The exact mechanisms by which these associations occur appear to be heterogeneous and are not yet well understood. The aim of this study was to identify and analyze publications in recent years to better understand the diagnosis and its contribution to monitoring APS among women with recurrent miscarriage (RM). This systematic review and meta-analysis was conducted using the PubMed and Web of Knowledge databases, with articles published between 2010 and 2014, according to the PRISMA statement. Of the 85 identified studies, nine were selected. Most of the studies reported an association between recurrent miscarriage and specific antiphospholipid antibodies, as anticardiolipin antibodies (aCL), lupus anticoagulant (LA), anti-β2-glycoprotein I antibodies (aβ2GPI) and antiphosphatidylserine (aPS), which showed a relationship with RM. The main result of the meta-analysis revealed association between antiphospholipid antibodies (aPLs) and/or APS compared to the patients with RM (OR: 0.279; 95% CI: 0.212-0.366) and APS cases compared to the patients with RM (OR: 0.083; 95% CI: 0.036-0.189). High heterogeneity among these studies (I=100.0%, p <0.001) was observed. In addition, there was no significant publication bias across studies according to Begg's test (p=0.230), although Egger's test (p=0.037) suggests significant publication bias. The funnel plot was slightly asymmetrical. Systematic review and meta-analysis demonstrated a positive association between antiphospholipid antibodies and/or antiphospholipid syndrome in patients with recurrent miscarriage.
Topics: Abortion, Habitual; Adult; Antibodies, Anticardiolipin; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Female; Humans; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Monitoring, Physiologic; Phosphatidylserines; Pregnancy; Publication Bias; Reference Standards
PubMed: 28985591
DOI: 10.1016/j.jri.2017.09.007 -
JBI Database of Systematic Reviews and... Aug 2017Osteosarcoma mostly occurs during the period of rapid bone growth in children and adolescents as high-grade osteosarcomas. Current treatment recommended for high-grade... (Review)
Review
BACKGROUND
Osteosarcoma mostly occurs during the period of rapid bone growth in children and adolescents as high-grade osteosarcomas. Current treatment recommended for high-grade non-metastatic and metastatic and/or relapsed osteosarcoma involves neoadjuvant multiagent conventional chemotherapy, followed by surgical resection of macroscopically detected tumor and postoperative adjuvant chemotherapy. However, residual micrometastatic deposits that develop following surgery have shown resistance to postoperative/adjuvant chemotherapy. Therefore, there is a critical need for more effective and innovative therapeutic approaches such as immune stimulatory agents. The most extensively studied immune stimulatory agent in the treatment of osteosarcoma is mifamurtide. The aim of this systematic review was to identify and synthesize the evidence on the effectiveness of mifamurtide in addition to standard chemotherapy on survival outcomes.
OBJECTIVES
To present the best available evidence on the treatment of high-grade non-metastatic and metastatic osteosarcoma with mifamurtide in addition to standard chemotherapy.
INCLUSION CRITERIA TYPES OF PARTICIPANTS
All populations of patients regardless of age, gender or ethnicity with high-grade, resectable, non-metastatic and metastatic osteosarcoma based on histological diagnosis.
TYPES OF INTERVENTIONS AND COMPARATORS
This review focused on intravenous infusion of either of the pharmaceutical formulations of mifamurtide (MTP-PE or L-MTP-PE) in addition to standard chemotherapy, and the comparator was chemotherapy alone.
TYPES OF STUDIES
This review considered any experimental study design including randomized controlled trials, non-randomized trials and quasi-experimental studies.
OUTCOMES
The primary outcomes of interest were event-free survival, overall survival and recurrence of osteosarcoma. Secondary outcomes that were considered included health-related quality of life and any mifamurtide-related adverse events.
SEARCH STRATEGY
A search for published and unpublished literature in English was undertaken (seven published literature databases, four unpublished literature databases, and three government agency and organizational websites were searched). Studies published between 1990 to June 2016 were considered. A three-step strategy was developed using MeSH terminology and keywords to ensure that all relevant studies were included related to this review.
METHODOLOGICAL QUALITY
The methodological quality of included studies was assessed by two reviewers, who appraised each study independently, using a standardized Joanna Briggs Institute (JBI) critical appraisal tool.
DATA EXTRACTION
Data was extracted from the studies that were identified as meeting the criteria for methodological quality using the standard JBI data extraction tool.
DATA SYNTHESIS
Due to the heterogeneity of populations and interventions in available studies, meta-analysis was not possible and results are presented in narrative form.
RESULTS
Three papers outlining two studies involving 802 patients evaluated the effectiveness of mifamurtide in addition of chemotherapy. Results indicated no significant difference in event-free survival between the addition of mifamurtide to standard chemotherapy regimen and chemotherapy alone, both in non-metastatic and metastatic osteosarcoma patients. There was a significant difference in progression-free survival favoring the addition of mifamurtide in pulmonary metastatic and/or relapsed osteosarcoma. There was no significant difference in overall survival between the addition of mifamurtide and chemotherapy alone in metastatic osteosarcoma; however there was a significant difference favoring the addition of mifamurtide in non-metastatic osteosarcoma patients. The addition of mifamurtide resulted in a significant difference in survival after relapse in pulmonary metastatic and/or relapsed osteosarcoma patients. Both studies reported on mifamurtide-related adverse events - the first was reported as toxicity which included haematological, hepatic, renal, gastrointestinal disorders, cardiac, rhythm and nervous system disorders, ear disorders and others (infection, fever; and performance status) in metastatic osteosarcoma patients. Results were similar across all combined treatment regimens. Although no statistical analysis was undertaken, the figures suggest there were no significant differences between the treatment regimens. In the other study, mifamurtide-related adverse events were reported as clinical toxic effects of mifamurtide in relapsed osteosarcoma, which included chills, fever and headache for the initial dose of mifamurtide, while for the subsequent doses of mifamurtide all patients reported toxicity as delayed fatigue.
CONCLUSIONS
The available evidence on the effectiveness of mifamurtide in addition to a standard chemotherapy regimen for the treatment of high-grade osteosarcoma is limited and therefore no definitive conclusions can be made.
Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adjuvants, Immunologic; Drug Therapy; Humans; Osteosarcoma; Phosphatidylethanolamines
PubMed: 28800058
DOI: 10.11124/JBISRIR-2016-003105 -
European Journal of Obstetrics,... Jun 2017Accurate and early identification of women at risk from alcohol consumption during pregnancy allows education and support programmes to be targeted at those most in... (Review)
Review
Accurate and early identification of women at risk from alcohol consumption during pregnancy allows education and support programmes to be targeted at those most in need. We aimed to conduct a systematic review to compare the efficacy of blood analysis and maternal self-report in detecting at risk women during pregnancy. This review investigated diagnostic accuracy. We searched four databases (Medline, Embase, Psychinfo and CINAHL) for relevant articles and conducted hand searches of recent issues of key journals in the field. No restriction was placed on inclusion in terms of publication date or language. Studies were deemed eligible if they were original research and included a direct comparison of the results of blood biomarker analysis and self-reported alcohol use for the detection of alcohol consumption in pregnant women. Quality appraisal of included studies was conducted using the QUADAS II tool. Eight studies met the inclusion criteria. Gamma-glutamyltransferase (GGT) was investigated in five studies, mean corpuscular volume (MCV) and phosphatidylethanol (PEth) in three studies and carbohydrate deficient transferrin (CDT), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and whole blood associated acetaldehyde assay (WBAA) were each investigated in two studies. Although all of the studies were rated of good methodological quality, none of the biomarkers had both high sensitivity and specificity when compared to self-report. There was some evidence that a combination of biomarkers, or combining biomarkers with self-report, increases accuracy. In summary, the blood biomarkers examined were of limited use in screening for low and moderate alcohol consumption in pregnancy when compared to self-report. However, certain biomarkers, such and CDT and PEth may complement self-report and help improve the accuracy of diagnosis.
Topics: Alanine Transaminase; Alcohol Drinking; Aspartate Aminotransferases; Biomarkers; Erythrocyte Indices; Female; Glycerophospholipids; Humans; MEDLINE; Pregnancy; Self Report; Sensitivity and Specificity; Transferrin; gamma-Glutamyltransferase
PubMed: 28426943
DOI: 10.1016/j.ejogrb.2017.04.005 -
Rheumatology (Oxford, England) Nov 2015To systematically review and establish the prevalence of antibody positivity in assays not currently included in the APS classification criteria to detect antibodies... (Review)
Review
OBJECTIVE
To systematically review and establish the prevalence of antibody positivity in assays not currently included in the APS classification criteria to detect antibodies directed against other phospholipids (PLs), PL binding proteins, coagulation factors and a mechanistic test for resistance of Annexin A5 (AnxA5) anticoagulant activity in APS and control populations.
METHODS
We searched PubMed and EMBASE using the key words APS, antiphospholipid antibodies, non-criteria, new assays, IgA anticardiolipin antibodies, lupus anticoagulant, anti-Domain I, IgA anti-β2-glycoprotein I antibodies, antiphosphatidylserine, anti-phosphatidylethanolamine, anti-phosphatidic acid, antiprothrombin, antiphosphatidylserine-prothtombin, anti-vimentin/cardiolipin complex and Annexin A5 resistance. Studies that met inclusion criteria to describe prevalence of non-criteria aPLs in APS patients (n > 10), disease and healthy control subjects were systematically examined.
RESULTS
We selected 16 retrospective studies of 1404 APS patients, 1839 disease control and 797 healthy controls. The highest prevalence of non-criteria aPLs in the largest number of patients with APS was found in IgA anti-β2GPI studies (129/229, 56.3%), AnxA5R (87/163, 53.4%) and IgG anti-Domain I (241/548, 44.0%).
CONCLUSION
Our finding of a significantly high prevalence of all non-criteria aPLs studied in patients with APS compared with controls was tempered by wide variation in sample size, retrospective collection, assay methodology and different determination of positivity. Therefore, prospective studies of sufficient size and appropriate methodology are required to evaluate the significance of these assays and their utility in the management of patients with APS.
Topics: Annexin A5; Antibodies, Anti-Idiotypic; Antiphospholipid Syndrome; Case-Control Studies; Humans; Immunoglobulin A; Immunoglobulin G; Phospholipids; Prevalence; Retrospective Studies; beta 2-Glycoprotein I
PubMed: 26152548
DOI: 10.1093/rheumatology/kev226 -
Alcohol and Alcoholism (Oxford,... Mar 2015The aim of this review was to focus on the knowledge of the role of lipin-1 in the pathogenesis of alcoholic fatty liver. (Review)
Review
AIMS
The aim of this review was to focus on the knowledge of the role of lipin-1 in the pathogenesis of alcoholic fatty liver.
METHODS
Systematic review of animal clinical and cell level studies related to the function of lipin-1 on alcoholic fatty liver, alcoholic hepatitis and alcoholic liver cirrhosis disease.
RESULT
Ethanol could increase the expression of lipin-1 through the AMPK-SREBP-1 signaling and dramatically increase the ratio of Lpin1β to Lpin1α by SIRT1-SFRS10-Lpin1β/α axis in the liver. Moreover, research has shown that over-expression of lipin-1 could also remarkably suppress very low density lipoprotein-triacylglyceride secretion. Last, lipin-1 has potent anti-inflammatory property.
CONCLUSION
In conclusion, lipin-1 has dual functions in lipid metabolism. In the cytoplasm, lipin-1β functions as a Mg(2+)-dependent phosphatidic acid phosphohydrolase (PAP) enzyme in triglyceride synthesis pathways. In the nucleus, lipin-1α acts as a transcriptional co-regulator to regulate the capacity of the liver for fatty acid oxidation and activity of the lipogenic enzyme. In hepatocytes of alcoholic fatty liver disease (AFLD), ethanol increases the expression of lipin-1 through the AMPK-SREBP-1 signaling and the Lpin1β/α ratio by SIRT1-SFRS10- Lpin1β/α axis. Of course, in addition to that, ethanol could also produce the PAP activity and interrupt the nucleus function of lipin-1. Furthermore, over-expression of lipin-1 could remarkably suppress very low-density lipoprotein-triacylglyceride (VLDL-TAG) secretion. In the end, endogenous lipin-1 has potent anti-inflammatory property. Increased synthesis of TAG, decreased fatty acid oxidation, impaired VLDL-TAG secretion and activated inflammatory factors act together to exacerbate the development of AFLD.
Topics: AMP-Activated Protein Kinases; Animals; Fatty Liver, Alcoholic; Hepatitis, Alcoholic; Lipid Metabolism; Lipoproteins, LDL; Liver; Liver Cirrhosis, Alcoholic; Mice; Nuclear Proteins; Phosphatidate Phosphatase; RNA-Binding Proteins; Serine-Arginine Splicing Factors; Signal Transduction; Sirtuin 1; Sterol Regulatory Element Binding Protein 1; Triglycerides
PubMed: 25595739
DOI: 10.1093/alcalc/agu102 -
International Journal of Gynecological... Jan 2015This study aimed to assess the diagnostic value of lysophosphatidic acid (LPA) in ovarian cancer. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aimed to assess the diagnostic value of lysophosphatidic acid (LPA) in ovarian cancer.
METHODS
A systematic review of related studies was performed; sensitivity, specificity, and other measures about the accuracy of serum LPA in the diagnosis of ovarian cancer were pooled using random-effects models. Summary receiver operating characteristic curve analysis was used to summarize the overall test performance.
RESULTS
Six studies involving 363 patients with ovarian cancer and 273 healthy control women met the inclusion criteria. The summary estimates for LPA in diagnosing ovarian cancer in the included studies were as follows: sensitivity, 0.94 [95% confidence interval (CI), 0.91-0.96]; specificity, 0.88 (95% CI, 0.83-0.91); and diagnostic odds ratio, 141.59 (95% CI, 52.1-384.63). The area under the curve and Q value for summary receiver operating characteristic curves were 0.97 and 0.92, respectively.
CONCLUSIONS
The LPA assay showed high accuracy and sensitivity for the diagnosis of ovarian cancer. The present study was limited by the small number of available studies and sample size; therefore, additional studies with a better design and larger samples are needed to further assess the diagnostic accuracy of LPA.
Topics: Biomarkers, Tumor; Case-Control Studies; Female; Humans; Lysophospholipids; Ovarian Neoplasms; Prognosis; ROC Curve
PubMed: 25398018
DOI: 10.1097/IGC.0000000000000319