-
Biomedicine & Pharmacotherapy =... Jan 2024Development of therapeutic agents that have fewer adverse effects and have higher efficacy for diseases, such as cancer, metabolic disorders, neurological diseases,... (Review)
Review
Development of therapeutic agents that have fewer adverse effects and have higher efficacy for diseases, such as cancer, metabolic disorders, neurological diseases, infections, cardiovascular diseases, and respiratory diseases, are required. Recent studies have focused on identifying novel sources for pharmaceutical molecules to develop therapies against these diseases. Among the sources for potentially new therapies, animal venom-derived molecules have generated much interest. Various animal venom-derived proteins and peptides have been isolated, identified, synthesized, and tested to develop drugs. Venom-derived peptides have several biomedical properties, such as proapoptotic, cell migration, and autophagy regulation activities in cancer cell models; induction of vasodilation by nitric oxide and regulation of angiotensin II; modification of insulin response by controlling calcium and potassium channels; regulation of pain receptor activity; modulation of immune cell activity; alteration of motor neuron activity; degradation or inhibition of β-amyloid plaque formation; antibacterial, antifungal, antiviral, and antiprotozoal activities; increase in sperm motility and potentiation of erectile function; reduction of intraocular pressure; anticoagulation, fibrinolytic, and antithrombotic activities; etc. This systematic review compiles these biomedical properties and potential biomedical applications of synthesized animal venom-derived peptides reported in the latest research. In addition, the limitations and areas of opportunity in this research field are discussed so that new studies can be developed based on the data presented.
Topics: Animals; Male; Venoms; Sperm Motility; Peptides; Angiotensin II
PubMed: 38113629
DOI: 10.1016/j.biopha.2023.116015 -
Panminerva Medica Mar 2024Sepsis-related mortality is decreasing over time after the introduction of "Surviving Sepsis Campaign" Guidelines in 2004. The last Guidelines version collects 93...
INTRODUCTION
Sepsis-related mortality is decreasing over time after the introduction of "Surviving Sepsis Campaign" Guidelines in 2004. The last Guidelines version collects 93 recommendations, but several interventions supported by randomized evidence of mortality reduction are not included.
EVIDENCE ACQUISITION
We performed a systematic review of all randomized controlled trials reporting a statistically significant mortality reduction in septic patients and compared the identified studies to the Surviving Sepsis Campaign Guidelines 2021 to highlight discrepancies.
EVIDENCE SYNTHESIS
We identified 83 randomized controlled trials (58 interventions) influencing mortality in sepsis. Only 9/58 of these interventions were included in the Guidelines: lactate measurement and lactate-guided hemodynamic management, procalcitonin-guided antibiotics discontinuation, balanced crystalloids as first choice fluids, albumin infusion, avoidance of starches, noradrenaline as first line vasopressor, vasopressin as an adjunctive vasopressor to noradrenaline, neuromuscular blocking agents in moderate-severe sepsis-associated acute respiratory distress syndrome, and corticosteroids use. Only 11/93 Guidelines recommendations were supported by randomized evidence with mortality difference. Five of the interventions with survival benefit in literature (vitamin C, terlipressin, polymyxin B, liberal transfusion strategy and immunoglobulins) were recommended to avoid in the Guidelines, while 44 interventions were not mentioned, including three interventions (esmolol, omega 3, and external warming) with at least two randomized controlled trials with a documented survival benefit.
CONCLUSIONS
Several discrepancies exist between the randomized controlled trials with mortality difference in septic patients and the latest Surviving Sepsis Campaign Guidelines. This systematic review can be of help for improving future guidelines and may guide research on specific promising topics.
Topics: Humans; Shock, Septic; Sepsis; Adrenal Cortex Hormones; Norepinephrine; Lactic Acid
PubMed: 38093626
DOI: 10.23736/S0031-0808.23.04986-8 -
Acta Cirurgica Brasileira 2023Vasoplegia, or vasoplegic shock, is a syndrome whose main characteristic is reducing blood pressure in the presence of a standard or high cardiac output. For the... (Meta-Analysis)
Meta-Analysis
PURPOSE
Vasoplegia, or vasoplegic shock, is a syndrome whose main characteristic is reducing blood pressure in the presence of a standard or high cardiac output. For the treatment, vasopressors are recommended, and the most used is norepinephrine. However, new drugs have been evaluated, and conflicting results exist in the literature.
METHODS
This is a systematic review of the literature with meta-analysis, written according to the recommendations of the PRISMA report. The SCOPUS, PubMed, and ScienceDirect databases were used to select the scientific articles included in the study. Searches were conducted in December 2022 using the terms "vasopressin," "norepinephrine," "vasoplegic shock," "postoperative," and "surgery." Meta-analysis was performed using Review Manager (RevMan) 5.4. The endpoint associated with the study was efficiency in treating vasoplegic shock and reduced risk of death.
RESULTS
In total, 2,090 articles were retrieved; after applying the inclusion and exclusion criteria, ten studies were selected to compose the present review. We found no significant difference when assessing the outcome mortality comparing vasopressin versus norepinephrine (odds ratio = 1.60; confidence interval 0.47-5.50), nor when comparing studies on vasopressin versus placebo. When we analyzed the length of hospital stay compared to the use of vasopressin and norepinephrine, we identified a shorter length of hospital stay in cases that used vasopressin; however, the meta-analysis did not demonstrate statistical significance.
CONCLUSIONS
Considering the outcomes included in our study, it is worth noting that most studies showed that using vasopressin was safe and can be considered in managing postoperative vasoplegic shock.
Topics: Humans; Vasopressins; Vasoconstrictor Agents; Norepinephrine; Vasoplegia; Blood Pressure
PubMed: 38055405
DOI: 10.1590/acb387523 -
Psychiatry Research Jan 2024Addiction is a substantial health concern; craving-the core symptom of addiction-is strongly associated with relapse. Transcranial direct current stimulation (tDCS) is a... (Meta-Analysis)
Meta-Analysis
Addiction is a substantial health concern; craving-the core symptom of addiction-is strongly associated with relapse. Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that reduces cravings by altering cortical excitability and connectivity in brain regions. This systematic review and meta-analysis was conducted (following the PRISMA guidelines) to evaluate the efficacy of tDCS in reducing cravings for substances. Our analysis included 43 randomized, sham-controlled trials involving 1,095 and 913 participants receiving tDCS and sham stimulation, respectively. We analyzed the changes in craving scores and found that tDCS led to a moderate reduction in cravings compared with the sham effects. This effect was particularly pronounced when bilateral stimulation was used, the anodal electrode was placed on the right dorsolateral prefrontal cortex, current intensities ranged from 1.5 to 2 mA, stimulation sessions lasted 20 minutes, and the electrodes size was ≥35 cm². Notably, tDCS effectively reduced cravings for opioids, methamphetamine, cocaine, and tobacco but not for alcohol or cannabis. Our findings indicate tDCS as a promising, noninvasive, and low-risk intervention for reducing cravings for opioids, methamphetamine, cocaine, and tobacco. Additional studies are warranted to refine stimulation parameters and evaluate the long-term efficacy of tDCS in managing substance cravings.
Topics: Humans; Transcranial Direct Current Stimulation; Craving; Prefrontal Cortex; Substance-Related Disorders; Methamphetamine; Cocaine; Double-Blind Method
PubMed: 38043411
DOI: 10.1016/j.psychres.2023.115621 -
PloS One 2023The association of maternal exposure to selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs) with the risk of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The association of maternal exposure to selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs) with the risk of system-specific congenital malformations in offspring remains unclear. We conducted a meta-analysis to examine this association and the risk difference between these two types of inhibitors.
METHODS
A literature search was performed from January 2000 to May 2023 using PubMed and Web of Science databases. Cohort and case-control studies that assess the association of maternal exposure to SSRIs or SNRIs with the risk of congenital abnormalities were eligible for the study.
RESULTS
Twenty-one cohort studies and seven case-control studies were included in the meta-analysis. Compared to non-exposure, maternal exposure to SNRIs is associated with a higher risk of congenital cardiovascular abnormalities (pooled OR: 1.64 with 95% CI: 1.36, 1.97), anomalies of the kidney and urinary tract (pooled OR: 1.63 with 95% CI: 1.21, 2.20), malformations of nervous system (pooled OR: 2.28 with 95% CI: 1.50, 3.45), anomalies of digestive system (pooled OR: 2.05 with 95% CI: 1.60, 2.64) and abdominal birth defects (pooled OR: 2.91 with 95%CI: 1.98, 4.28), while maternal exposure to SSRIs is associated with a higher risk of congenital cardiovascular abnormalities (pooled OR: 1.25 with 95%CI: 1.20, 1.30), anomalies of the kidney and urinary tract (pooled OR: 1.14 with 95%CI: 1.02, 1.27), anomalies of digestive system (pooled OR: 1.11 with 95%CI: 1.01, 1.21), abdominal birth defects (pooled OR: 1.33 with 95%CI: 1.16, 1.53) and musculoskeletal malformations (pooled OR: 1.44 with 95%CI: 1.32, 1.56).
CONCLUSIONS
SSRIs and SNRIs have various teratogenic risks. Clinicians must consider risk-benefit ratios and patient history when prescribing medicines.
Topics: Female; Humans; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors; Maternal Exposure; Norepinephrine; Serotonin; Cardiovascular Abnormalities
PubMed: 38019759
DOI: 10.1371/journal.pone.0294996 -
Journal of Human Hypertension Feb 2024Blood pressure (BP) management reduces the risk of cardiovascular disease (CVD). The renin-angiotensin-aldosterone system (RAAS) plays an important role in regulating... (Meta-Analysis)
Meta-Analysis Review
Blood pressure (BP) management reduces the risk of cardiovascular disease (CVD). The renin-angiotensin-aldosterone system (RAAS) plays an important role in regulating and maintaining blood volume and pressure. This analysis aimed to investigate the effect of exercise training on plasma renin, angiotensin-II and aldosterone, epinephrine, norepinephrine, urinary sodium and potassium, BP and heart rate (HR). We systematically searched PubMed, Web of Science, and the Cochrane Library of Controlled Trials until 30 November 2022. The search strategy included RAAS key words in combination with exercise training terms and medical subject headings. Manual searching of reference lists from systematic reviews and eligible studies completed the search. A random effects meta-analysis model was used. Eighteen trials with a total of 803 participants were included. After exercise training, plasma angiotensin-II (SMD -0.71; 95% CI -1.24, -0.19; p = 0.008; n = 9 trials), aldosterone (SMD -0.37; 95% CI -0.65, -0.09; p = 0.009; n = 8 trials) and norepinephrine (SMD -0.82; 95% CI -1.18, -0.46; p < 0.001; n = 8 trials) were reduced. However, plasma renin activity, epinephrine, and 24-h urinary sodium and potassium excretion remained unchanged with exercise training. Systolic BP was reduced (MD -6.2 mmHg; 95% CI -9.9, -2.6; p = 0.001) as was diastolic BP (MD -4.5 mmHg; 95% CI -6.9, -2.1; p < 0.001) but not HR (MD -3.0 bpm; 95% CI -6.0, 0.4; p = 0.053). Exercise training may reduce some aspects of RAAS and sympathetic nervous system activity, and this explains some of the anti-hypertensive response.
Topics: Humans; Renin-Angiotensin System; Renin; Aldosterone; Blood Pressure; Norepinephrine; Epinephrine; Angiotensin II; Potassium; Sodium; Exercise
PubMed: 38017087
DOI: 10.1038/s41371-023-00872-4 -
JAMA Network Open Oct 2023Hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) are associated with significant mortality and morbidity. The effectiveness and...
IMPORTANCE
Hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) are associated with significant mortality and morbidity. The effectiveness and safety of oral urea for SIADH are still debated.
OBJECTIVE
To evaluate the efficacy and safety of urea for the treatment of SIADH.
EVIDENCE REVIEW
A systematic search of Medline and Embase was conducted for controlled and uncontrolled studies of urea for SIADH in adult patients. The primary outcome was serum sodium concentration after treatment. Secondary outcomes included the proportion of patients with osmotic demyelination syndrome (ODS), intracranial pressure, and resource use such as length of stay.
FINDINGS
Twenty-three studies involving 537 patients with SIADH were included, of which 462 were treated with urea. The pooled mean baseline serum sodium was 125.0 mmol/L (95% CI, 122.6-127.5 mmol/L). The median treatment duration with oral urea was 5 days. Urea increased serum sodium concentration by a mean of 9.6 mmol/L (95% CI, 7.5-11.7 mmol/L). The mean increase in serum sodium after 24 hours was 4.9 mmol/L (95% CI, 0.5-9.3 mmol/L). Adverse events were few, mainly consisting of distaste or dysgeusia, and no case of ODS was reported. Resource use was too infrequently reported to be synthesized.
CONCLUSIONS AND RELEVANCE
In this systematic review of the use of urea in SIADH and despite the lack of randomized clinical trials, lower-quality evidence was identified that suggests that urea may be an effective, safe, and inexpensive treatment modality that warrants further exploration.
Topics: Adult; Humans; Urea; Inappropriate ADH Syndrome; Vasopressins; Demyelinating Diseases; Sodium
PubMed: 37902751
DOI: 10.1001/jamanetworkopen.2023.40313 -
Psychopharmacology Feb 2024The selective serotonin and norepinephrine reuptake inhibitor venlafaxine is among the most prescribed antidepressant drugs worldwide and, according to guidelines, its... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The selective serotonin and norepinephrine reuptake inhibitor venlafaxine is among the most prescribed antidepressant drugs worldwide and, according to guidelines, its dose titration should be guided by drug-level monitoring of its active moiety (AM) which consists of venlafaxine (VEN) plus active metabolite O-desmethylvenlafaxine (ODV). This indication of therapeutic drug monitoring (TDM), however, assumes a clear concentration/effect relationship for a drug, which for VEN has not been systematically explored yet.
OBJECTIVES
We performed a systematic review and meta-analysis to investigate the relationship between blood levels, efficacy, and adverse reactions in order to suggest an optimal target concentration range for VEN oral formulations for the treatment of depression.
METHODS
Four databases (MEDLINE (PubMed), PsycINFO, Web of Science Core Collection, and Cochrane Library) were systematically searched in March 2022 for relevant articles according to a previously published protocol. Reviewers independently screened references and performed data extraction and critical appraisal.
RESULTS
High-quality randomized controlled trials investigating concentration/efficacy relationships and studies using a placebo lead-in phase were not found. Sixty-eight articles, consisting mostly of naturalistic TDM studies or small noncontrolled studies, met the eligibility criteria. Of them, five cohort studies reported a positive correlation between blood levels and antidepressant effects after VEN treatment. Our meta-analyses showed (i) higher AM and (ii) higher ODV concentrations in patients responding to VEN treatment when compared to non-responders (n = 360, k = 5). AM concentration-dependent occurrence of tremor was reported in one study. We found a linear relationship between daily dose and AM concentration within guideline recommended doses (75-225 mg/day). The population-based concentration ranges (25-75% interquartile) among 11 studies (n = 3200) using flexible dosing were (i) 225-450 ng/ml for the AM and (ii) 144-302 ng/ml for ODV. One PET study reported an occupancy of 80% serotonin transporters for ODV serum levels above 85 ng/ml. Based on our findings, we propose a therapeutic reference range for AM of 140-600 ng/ml.
CONCLUSION
VEN TDM within a range of 140 to 600 ng/ml (AM) will increase the probability of response in nonresponders. A titration within the proposed reference range is recommended in case of non-response at lower drug concentrations as a consequence of VEN's dual mechanism of action via combined serotonin and norepinephrine reuptake inhibition. Drug titration towards higher concentrations will, however, increase the risk for ADRs, in particular with supratherapeutic drug concentrations.
Topics: Humans; Antidepressive Agents; Depression; Desvenlafaxine Succinate; Norepinephrine; Reference Values; Serotonin; Venlafaxine Hydrochloride
PubMed: 37857898
DOI: 10.1007/s00213-023-06484-7 -
International Journal of Molecular... Sep 2023Cocaine abuse is a serious public health problem as this drug exerts a plethora of functional and histopathological changes that potentially lead to death. Cocaine... (Review)
Review
Cocaine abuse is a serious public health problem as this drug exerts a plethora of functional and histopathological changes that potentially lead to death. Cocaine causes complex multiorgan toxicity, including in the heart where the blockade of the sodium channels causes increased catecholamine levels and alteration in calcium homeostasis, thus inducing an increased oxygen demand. Moreover, there is evidence to suggest that mitochondria alterations play a crucial role in the development of cocaine cardiotoxicity. We performed a systematic review according to the Preferred Reporting Items for Systemic Reviews and Meta-Analysis (PRISMA) scheme to evaluate the mitochondrial mechanisms determining cocaine cardiotoxicity. Among the initial 106 articles from the Pubmed database and the 17 articles identified through citation searching, 14 final relevant studies were extensively reviewed. Thirteen articles included animal models and reported the alteration of specific mitochondria-dependent mechanisms such as reduced energy production, imbalance of membrane potential, increased oxidative stress, and promotion of apoptosis. However, only one study evaluated human cocaine overdose samples and observed the role of cocaine in oxidative stress and the induction of apoptosis though mitochondria. Understanding the complex processes mediated by mitochondria through forensic analysis and experimental models is crucial for identifying potential therapeutic targets to mitigate or reverse cocaine cardiotoxicity in humans.
Topics: Animals; Humans; Cardiotoxicity; Cocaine; Cocaine-Related Disorders; Heart; Mitochondria; Oxidative Stress
PubMed: 37833964
DOI: 10.3390/ijms241914517 -
Journal of Forensic and Legal Medicine Nov 2023It is generally believed that the use of alcohol and cocaine alone and especially in combination elicits aggression and violent behaviour. Though there is overwhelming... (Review)
Review
It is generally believed that the use of alcohol and cocaine alone and especially in combination elicits aggression and violent behaviour. Though there is overwhelming proof that heavy alcohol use is associated with violence, this is not the case for cocaine. Still, in the popular press and by spokesmen of the police, cocaine use is seen as a cause of violent incidents. In the current systematic review, available data from human studies on the relation between cocaine and violent behaviour is presented. In particular, we present scientific data on the acute induction of violence by cocaine alone, as well as, that by the combination of cocaine and alcohol known to be frequently used simultaneously. RESULTS: show that there is only weak scientific evidence for the acute induction of violent behaviour by cocaine, either when used alone or in combination with alcohol. Based on these data we were also able to refute misconceptions about the relation between cocaine and violence published in the popular press and governmental reports, because it appeared that there was hardly any empirical support for this widely shared opinion. Probably, contextual factors, including cocaine use disorder and personality disorder, may better explain the assumed association between cocaine and violence.
Topics: Humans; Cocaine; Aggression; Violence; Substance-Related Disorders; Cocaine-Related Disorders; Ethanol
PubMed: 37832170
DOI: 10.1016/j.jflm.2023.102597