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American Journal of Obstetrics and... Feb 2022There has been increasing research momentum to identify new therapeutic agents for the prevention or treatment of preeclampsia, drugs that can affect the underlying...
There has been increasing research momentum to identify new therapeutic agents for the prevention or treatment of preeclampsia, drugs that can affect the underlying disease pathophysiology. Molecular targets of candidate treatments include oxidative stress, antiangiogenic factors, and the angiotensin, nitric oxide, and proinflammatory pathways. The proposed treatments undergoing preclinical and clinical trial evaluation are thought to act on placental or endothelial disease or both. Most have adopted the pragmatic strategy of repurposing drugs. Of all the therapeutic agents proposed, pravastatin has received the most interest. There are preclinical studies showing that it has pleiotropic actions that favorably impact on multiple molecular targets and can resolve a preeclampsia phenotype in many animal models. An early phase clinical trial suggests that it may have therapeutic activity. Several large prevention trials are planned or ongoing and, when completed, could definitively address whether pravastatin can prevent preeclampsia. Proton-pump inhibitors, metformin, and sulfasalazine are other drugs with preclinical evidence of multiple molecular actions that could resolve the pathophysiology of preeclampsia. These agents are also currently being evaluated in clinical trials. There have been many recent preclinical studies identifying the potential of numerous natural compounds to treat preeclampsia, such as plant extracts and micronutrients that have potent anti-inflammatory or antioxidant activity. Recent preclinical studies have also proposed novel molecular-targeted strategies, such as monoclonal antibodies targeting tumor necrosis factor alpha, placental growth factor, and short interfering RNA technology, to silence the gene expression of soluble fms-like tyrosine kinase-1 or angiotensinogen. Other treatment approaches that have transitioned to human trials (ranging from single-arm to phase III trials that have been completed or are ongoing) include folic acid, nitric oxide donors (such as L-arginine), recombinant antithrombin III, digoxin immune antigen-binding fragment, and melatonin. There have been case series showing the removal of circulating soluble fms-like tyrosine kinase-1 may help stabilize the disease and prolong pregnancy. Interestingly, there are case reports suggesting that monoclonal antibody eculizumab (complement inhibitor) may have therapeutic potential. If new agents are discovered that are proven to be effective in preventing or treating preeclampsia, the potential to improve global maternal and perinatal health will be significant.
Topics: Antibodies, Monoclonal; Antioxidants; Antithrombin III; Biological Products; Blood Component Removal; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Metformin; Micronutrients; Placenta Growth Factor; Plant Extracts; Pravastatin; Pre-Eclampsia; Pregnancy; Proton Pump Inhibitors; RNA, Small Interfering; Recombinant Proteins; Sulfasalazine; Vascular Endothelial Growth Factor Receptor-1
PubMed: 32946849
DOI: 10.1016/j.ajog.2020.09.014 -
Pediatrics Jun 2021Functional abdominal pain disorders (FAPDs) are common in childhood, impacting quality of life and school attendance. There are several compounds available for the...
CONTEXT
Functional abdominal pain disorders (FAPDs) are common in childhood, impacting quality of life and school attendance. There are several compounds available for the treatment of pediatric FAPDs, but their efficacy and safety are unclear because of a lack of head-to-head randomized controlled trials (RCTs).
OBJECTIVE
To systematically review the efficacy and safety of the pharmacologic treatments available for pediatric FAPDs.
DATA SOURCES
Electronic databases were searched from inception to February 2021.
STUDY SELECTION
RCTs or systematic reviews were included if the researchers investigated a study population of children (4-18 years) in whom FAPDs were treated with pharmacologic interventions and compared with placebo, no treatment, or any other agent.
DATA EXTRACTION
Two reviewers independently performed data extraction and assessed their quality. Any interresearcher disagreements in the assessments were resolved by a third investigator.
RESULTS
Seventeen articles representing 1197 children with an FAPD were included. Trials investigating antispasmodics, antidepressants, antibiotics, antihistaminic, antiemetic, histamine-2-receptor antagonist, 5-HT4-receptor agonist, melatonin, and buspirone were included. No studies were found on treatment with laxatives, antidiarrheals, analgesics, antimigraines, and serotonergics.
LIMITATIONS
The overall quality of evidence on the basis of the Grading of Recommendations, Assessment, Development and Evaluations system was very low to low.
CONCLUSIONS
On the basis of current evidence, it is not possible to recommend any specific pharmacologic agent for the treatment of pediatric FAPDs. However, agents such as antispasmodics or antidepressants can be discussed in daily practice because of their favorable treatment outcomes and the lack of important side effects. High-quality RCTs are necessary to provide adequate pharmacologic treatment. For future intervention trials, we recommend using homogenous outcome measures and instruments, a large sample size, and long-term follow-up.
Topics: Abdominal Pain; Child; Drug-Related Side Effects and Adverse Reactions; Humans; Treatment Outcome
PubMed: 34045320
DOI: 10.1542/peds.2020-042101 -
Journal of Critical Care Oct 2020To assess the efficacy and safety of suvorexant for the prevention of delirium during acute hospitalization.
PURPOSE
To assess the efficacy and safety of suvorexant for the prevention of delirium during acute hospitalization.
MATERIALS AND METHODS
Pubmed (1946 to December 2019) and Embase (1947 to December 2019) were queried using the search term combination: delirium, confusion, cognitive defect, encephalopathy, critically ill patient, critical illness, or hospitalization and suvorexant or orexin receptor antagonist. Studies analyzed for relevance evaluated clinical outcomes of patients treated with suvorexant for prevention of delirium. Studies appropriate to the objective were evaluated, including two randomized controlled trials and four retrospective studies.
RESULTS
In acutely hospitalized patients, treatment with suvorexant 15 to 20 mg alone or in combination with ramelteon resulted in a reduction in development of delirium, time until delirium onset, and length of hospital stay. When assessed, suvorexant was well tolerated and adverse effects were no worse than placebo.
CONCLUSION
Based on the reviewed literature, suvorexant has shown positive outcomes in the prevention of delirium during an acute hospitalization. Larger trials comparing the efficacy of suvorexant to other sleep modulating options are necessary to further delineate its role for the prevention of delirium.
Topics: Aged; Aged, 80 and over; Azepines; Critical Care; Critical Illness; Delirium; Drug Therapy, Combination; Female; Humans; Indenes; Length of Stay; Male; Middle Aged; Orexin Receptor Antagonists; Randomized Controlled Trials as Topic; Receptor, Melatonin, MT1; Receptor, Melatonin, MT2; Retrospective Studies; Sleep; Sleep Initiation and Maintenance Disorders; Treatment Outcome; Triazoles
PubMed: 32480359
DOI: 10.1016/j.jcrc.2020.05.006 -
American Journal of Perinatology May 2020Whether melatonin receptor 1B () variants are implicated in gestational diabetes mellitus (GDM) remains unclear. Therefore, we performed this meta-analysis to obtain a... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Whether melatonin receptor 1B () variants are implicated in gestational diabetes mellitus (GDM) remains unclear. Therefore, we performed this meta-analysis to obtain a more conclusive result on associations between variants and GDM.
STUDY DESIGN
Literature research was performed in PubMed, Web of Science, Embase, and China National Knowledge Infrastructure. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.
RESULTS
A total of 17 studies were eligible for analyses. Pooled overall analyses showed that rs1387153 (dominant model: = 0.0002, OR = 0.78, 95% CI: 0.68-0.89; recessive model: < 0.0001, OR = 1.46, 95% CI: 1.24-1.73; allele model: < 0.0001, OR = 0.78, 95% CI: 0.72-0.84), rs4753426 (recessive model: = 0.01, OR = 1.75, 95% CI: 1.14-2.68; allele model: = 0.01, OR = 0.69, 95% CI: 0.51-0.93), and rs10830963 (dominant model: < 0.0001, OR = 0.72, 95% CI: 0.65-0.78; recessive model: < 0.0001, OR = 1.56, 95% CI: 1.40-1.74; allele model: < 0.0001, OR = 0.73, 95% CI: 0.69-0.78) variants were all significantly associated with the susceptibility to GDM. Further subgroup analyses by ethnicity of participants yielded similar positive results.
CONCLUSION
Our findings indicated that rs1387153, rs4753426, and rs10830963 variants might serve as genetic biomarkers of GDM.
Topics: Diabetes, Gestational; Female; Genetic Markers; Genetic Predisposition to Disease; Genetic Variation; Humans; Pregnancy; Receptor, Melatonin, MT2
PubMed: 30991439
DOI: 10.1055/s-0039-1685446 -
Molecular Pain 2024Nociception related salivary biomolecules can be useful patients who are not able to self-report pain. We present the existing evidence on this topic using the... (Review)
Review
Nociception related salivary biomolecules can be useful patients who are not able to self-report pain. We present the existing evidence on this topic using the PRISMA-ScR guidelines and a more focused analysis of cortisol change after cold pain induction using the direction of effect analysis combined with risk of bias analysis using ROBINS-I. Five data bases were searched systematically for articles on adults with acute pain secondary to disease, injury, or experimentally induced pain. Forty three articles met the inclusion criteria for the general review and 11 of these were included in the cortisol-cold pain analysis. Salivary melatonin, kallikreins, pro-inflammatory cytokines, soluable TNF-α receptor II, secretory IgA, testosterone, salivary α-amylase (sAA) and, most commonly, cortisol have been studied in relation to acute pain. There is greatest information about cortisol and sAA which both rise after cold pain when compared with other modalities. Where participants have been subjected to both pain and stress, stress is consistently a more reliable predictor of salivary biomarker change than pain. There remain considerable challenges in identifying biomarkers that can be used in clinical practice to guide the measurement of nociception and treatment of pain. Standardization of methodology and researchers' greater awareness of the factors that affect salivary biomolecule concentrations are needed to improve our understanding of this field towards creating a clinically relevant body of evidence.
Topics: Adult; Humans; Hydrocortisone; Acute Pain; Saliva; Nociception; Salivary alpha-Amylases; Biomarkers; Stress, Psychological
PubMed: 38385158
DOI: 10.1177/17448069241237121 -
Journal of Anxiety Disorders Jan 2020Treatments for Obsessive-Compulsive Disorder (OCD) have greatly improved over time. However, some patients do not respond to current interventions and many are left with...
BACKGROUND
Treatments for Obsessive-Compulsive Disorder (OCD) have greatly improved over time. However, some patients do not respond to current interventions and many are left with residual symptoms even if they are 'responders'. There is increasing evidence that individuals with OCD frequently report delayed bedtimes and are at elevated risk for Delayed Sleep Phase Disorder (DSPD). Therefore, it is logical to ask whether interventions addressing disruptions in sleep timing and circadian rhythms would lead to reductions in OCD symptoms. A prior study from our group showed that behaviorally shifting sleep timing resulted in significant symptom reduction in a treatment resistant OCD patient.
OBJECTIVES
Extending prior findings, this manuscript presents quantitative data from case studies which tested the use of a pharmacological intervention that targets melatonin receptors. Specifically, the case studies reviewed herein utilized the melatonin analog and melatonergic MT1 and MT2 receptor agonist, Agomelatine.
METHODS
A literature review revealed 10 cases which have used Agomelatine for OCD.
RESULTS
Seven of the cases were reported to have sleep and/or circadian disruptions prior to treatment. These cases OCD symptom reductions between 46%-90%. In contrast, three additional cases without pre-treatment sleep and/or circadian disruptions did not respond to the intervention.
DISCUSSION
There is growing evidence that disruptions in sleep and circadian rhythms may contribute to the maintenance of OCD. Further work is warranted.
Topics: Acetamides; Adolescent; Adult; Female; Humans; Male; Obsessive-Compulsive Disorder; Receptors, Melatonin; Treatment Outcome; Young Adult
PubMed: 31877423
DOI: 10.1016/j.janxdis.2019.102173 -
International Journal of Molecular... Apr 2021Myeloid differentiation 88 (MyD88) is a well-established inflammatory adaptor protein. It is one of the essential downstream proteins of the toll-like receptor 4 (TLR4)...
Myeloid differentiation 88 (MyD88) is a well-established inflammatory adaptor protein. It is one of the essential downstream proteins of the toll-like receptor 4 (TLR4) signaling pathway. TLRs are pattern recognition receptors that are usually activated by the damage-associated molecular pattern molecules (DAMPs). Sterile inflammation is triggered by the endogenous DAMPs released in response to global cerebral ischemia and from extravasated blood after subarachnoid hemorrhage (SAH). In this review, we highlight the importance of the neuroinflammatory role of the MyD88 in the SAH. We also explore a few possible pharmacological agents that can be used to decrease SAH-associated neuroinflammation by modulating the MyD88 dependent functions. Pharmacological agents such as flavonoids, melatonin, fluoxetine, pentoxifylline and progesterone have been investigated experimentally to reduce the SAH-associated inflammation. Inhibition of the MyD88 not only reduces the expression of pro-inflammatory cytokines, but also potentially inhibits other processes that can augment the SAH associated inflammation. Further investigations are required to translate these findings in the clinical setting.
Topics: Animals; Humans; Inflammation; Myeloid Differentiation Factor 88; Receptors, Pattern Recognition; Subarachnoid Hemorrhage
PubMed: 33919485
DOI: 10.3390/ijms22084185