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Clinical Nutrition ESPEN Jun 2023The inflammatory process is a response mechanism to any stressor agent. Emerging novel therapeutic options derived mainly from natural products such as bromelain have... (Review)
Review
BACKGROUND AND AIMS
The inflammatory process is a response mechanism to any stressor agent. Emerging novel therapeutic options derived mainly from natural products such as bromelain have been used to reduce the significant side effects of available anti-inflammatory drugs. Bromelain is an enzyme complex derived from Ananas comosus, known for its anti-inflammatory potential and good tolerance. Therefore, the aim was to assess whether bromelain supplementation exerts anti-inflammatory effects in adults.
METHODS
The systematic review was registered in PROSPERO (n° CRD42020221395), and the search was performed in MEDLINE, Scopus, Web of Science, and Cochrane Library. The terms used in the search were: "bromelains", "bromelain", "randomized clinical trial", and "clinical trial". Eligibility criteria were: randomized clinical trials with participants aged 18 years or over, of both sexes, who received supplementation with bromelain alone or in combination with other oral compounds, with an evaluation of inflammatory parameters as primary and secondary outcomes, published in English, Portuguese or Spanish.
RESULTS
1375 studies were retrieved, of which 269 were duplicates. Seven (7) randomized controlled trials were eligible for the systematic review. In most studies, supplementation with bromelain, isolated or in combined therapy, reduced inflammatory parameters. Regarding the reduction of inflammatory parameters among studies with associated bromelain, two presented reduction of inflammatory parameters, while in the evaluation of bromelain treated alone, two studies also showed reduction. In relation to doses supplemented, the studies with associated bromelain ranged from 99.9 to 1200 mg/day and the supplementation time ranged from 3 to 16 weeks. Moreover, the inflammatory parameters evaluated were: IL-12, PGE-2, COX-2, IL-6, IL-8, TNF-α, IL-1β, IL-10, CRP, NFγ B1, PPAR-α, TNF, TRAF, MCP-1 and adiponectin. In studies with isolated bromelain supplementation, it ranged from 200 to 1050 mg/day for 1 week to 16 weeks. Markers associated with inflammation varied between studies, including IL-2, IL-5, IL-6, IL-8, IL-10, IL-13, IFNγ and MCP-1, PGE-2, CRP and fibrinogen. Eleven (11) participants experienced side effects, and two discontinued treatment in the studies. The reported adverse effects were mainly gastrointestinal but well tolerated.
CONCLUSION
The general effect of bromelain supplementation on inflammation is inconsistent because of population heterogeneity, doses used, treatment duration, and parameters evaluated. The observed effects are punctual and isolated, and further standardization is needed to establish doses, supplementation time, and which type of inflammatory condition is indicated.
Topics: Male; Adult; Female; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Inflammation; Anti-Inflammatory Agents; Dietary Supplements
PubMed: 37202035
DOI: 10.1016/j.clnesp.2023.02.028 -
Advances in Clinical and Experimental... Oct 2023Psychosis is a very common feature of Alzheimer's disease (AD) that can emerge as the neurodegenerative disease progresses. The 5-hydroxytryptamine (5-HT2A) receptors... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of negative allosteric modulators of 5-hydroxytryptamine 2A receptors in the treatment of Alzheimer's disease psychosis: A systematic review and meta-analysis.
BACKGROUND
Psychosis is a very common feature of Alzheimer's disease (AD) that can emerge as the neurodegenerative disease progresses. The 5-hydroxytryptamine (5-HT2A) receptors are located postsynaptically to serotonergic neurons in the frontal cortex and mediate both excitatory and inhibitory neurotransmissions. However, the effectiveness and tolerance of negative modulators of 5-HT2A receptors in Alzheimer's disease psychosis (ADP) are uncertain.
OBJECTIVES
To detect the negative modulators of the 5-HT2A receptor as a cure for ADP.
MATERIAL AND METHODS
The primary outcome indicator was the total Neuropsychiatric Inventory (NPI) score. Other prognostic indicators included Mini-Mental State Examination (MMSE), the Katz Index of Independence in Activities of Daily Living (KATZ), the discontinuation rate, and adverse events.
RESULTS
Compared to placebo, 5-HT2A inverse agonists significantly reduced the NPI total score, the KATZ and the MMSE score. The pooled odds ratio (OR) was 1.64 (95% confidence interval (95% CI): 1.01-2.65) and the heterogeneity variance was estimated at Tau2 = 0.52 with an I2 value of 90%, a χ2 value of 111.31, p = 0.04, and z-value of 2.01. The risk difference (RD) between the 5-HT2A receptor negative modulators and placebo groups was 0.12 (95% CI: 0.00-0.24) and the heterogeneity was estimated at Tau2 = 0.03, χ2 value of 127.23, degrees of freedom (df) value of 9, I2 value of 93%, z-value of 1.92, and p-value of 0.01 (<0.05).
CONCLUSION
Our results suggest that negative modulators of 5-HT2A receptors are beneficial and well-tolerated in the treatment of ADP.
Topics: Humans; Alzheimer Disease; Serotonin; Neurodegenerative Diseases; Activities of Daily Living; Drug Inverse Agonism; Receptor, Serotonin, 5-HT2A; Psychotic Disorders
PubMed: 37166012
DOI: 10.17219/acem/161159 -
Neurochemical Research Aug 2023Peripheral neuropathies caused by the peripheral nervous system (PNS) damage can occur due to trauma and other disorders. They present as altered sensation, weakness,... (Meta-Analysis)
Meta-Analysis Review
Peripheral neuropathies caused by the peripheral nervous system (PNS) damage can occur due to trauma and other disorders. They present as altered sensation, weakness, autonomic symptoms, and debilitating pain syndrome with a wide range of clinical signs. Acetyl-L-Carnitine (ALCAR) is a biological compound with essential roles in mitochondrial oxidative metabolism and anti-oxidant effects that protects mitochondria from oxidative damage and inhibits apoptosis caused by mitochondrial damage. This study is a systematic review and meta-analysis of the effects of ALCAR on peripheral nerve injuries. This review examines studies on treating traumatic peripheral neuropathies in which ALCAR is administered to rats with sciatic nerve injury with an appropriate control group. The articles were divided based on the mode of ALCAR administration. If one method was used in more than one article, their results were entered in the "Revman5.4" software and were meta-analyzed. Studies were selected from 1994 to 2018 on rats with varying physical injuries to their sciatic nerves. In one study, ALCAR was provided to rats in their drinking water, while in other studies, ALCAR was injected intra-peritoneally. Different mechanisms of ALCAR actions have been suggested in this study, but the underpinnings of the neuroprotective effects of ALCAR are still unclear. Further studies are mandatory to clarify the actual mechanisms of the neuroprotective activity of ALCAR. Based on the results of existing studies, ALCAR effectively increases the tolerance threshold of thermal and mechanical stimuli, reduces latency, and reduces apoptosis; finally, adjusting the dose and duration of administration may increase the dose and duration axon diameter.
Topics: Animals; Rats; Acetylcarnitine; Nerve Regeneration; Peripheral Nerve Injuries; Sciatic Nerve
PubMed: 37037995
DOI: 10.1007/s11064-023-03911-1 -
Supportive Care in Cancer : Official... Mar 2023To evaluate the effectiveness and safety of oral supplementation as a radioprotective intervention in the management of radiation dermatitis (RD). (Meta-Analysis)
Meta-Analysis
PURPOSE
To evaluate the effectiveness and safety of oral supplementation as a radioprotective intervention in the management of radiation dermatitis (RD).
METHODS
Systematic review and meta-analysis. Six databases and the gray literature were searched for randomized controlled clinical trials (RCTs). Meta-analysis was performed only with studies that evaluated the same intervention. Methodology of included studies was evaluated by the Cochrane risk-of-bias tool for randomized trials (RoB 2.0), and the certainty of evidence was assessed by the GRADE instrument.
RESULTS
Seventeen RCTs were included in this review. These evaluated different types of oral supplementations. Findings from three meta-analyses demonstrated no significant benefits to the more severe grades of RD, as oral curcuminoids (RR, 0.59; 95% CI, 0.27 to 1.29; P = 0.19; I = 88%), glutamine (RR, 0.40; 95% CI, 0.15 to 1.03; P = 0.06; I = 78%) or Wobe-Mugos (RR, 0.57; 95% CI, 0.29 to 1.14; P = 0.11; I = 72%). Also, the certainty of the evidence of outcomes evaluated was moderate or low. Except for a few gastrointestinal adverse events, oral supplementation was well tolerated.
CONCLUSION
Most oral supplements cannot yet be recommended to manage RD due to insufficient or conflicting evidence. However, despite no significant results, glutamine was shown to be a promising substance in terms of the potential radioprotective effect and may be well tolerated. These results suggest that more RCTs with larger samples are needed to evaluate the efficacy, safety, and tolerance of glutamine in the management of RD.
Topics: Humans; Glutamine; Neoplasms; Radiodermatitis; Dietary Supplements
PubMed: 36976404
DOI: 10.1007/s00520-023-07685-8 -
Chronic Respiratory Disease 2023The rationale for additional treatment with short-acting bronchodilators combined with long-acting bronchodilators for patients with chronic obstructive pulmonary... (Meta-Analysis)
Meta-Analysis
The efficacy and safety of additional treatment with short-acting muscarinic antagonist combined with long-acting beta-2 agonist in stable patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis.
BACKGROUND
The rationale for additional treatment with short-acting bronchodilators combined with long-acting bronchodilators for patients with chronic obstructive pulmonary disease (COPD) is not adequately studied.
METHODS
We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of a short-acting muscarinic antagonist (SAMA) therapy combined with a long-acting beta-2 agonist (LABA) in patients with stable COPD. Pulmonary function, dyspnea, health-related quality of life, exercise tolerance, physical activity, exacerbations of COPD, and adverse events during regular use were set as outcomes of interest.
RESULTS
We included five controlled trials including two sets of publicly available online data without article publications for the meta-analysis. Additional use of SAMA plus LABA showed a significant improvement in the peak response in FEV (mean difference (MD) 98.70 mL, < .00001), transitional dyspnea index score (MD .85, = .02), and St George's Respiratory Questionnaire score (MD -2.00, = .008) compared to LABA treatment. There was no significant difference in the risk of exacerbation of COPD ( = .20) and only a slight trend of increased severe adverse events (OR: 2.16, = .08) and cardiovascular events (OR: 2.38, = .06).
CONCLUSION
Additional treatment with SAMA combined with LABA could be a feasible choice due to its efficacy and safety.
Topics: Humans; Muscarinic Antagonists; Bronchodilator Agents; Adrenergic beta-2 Receptor Agonists; Quality of Life; Pulmonary Disease, Chronic Obstructive; Administration, Inhalation; Dyspnea
PubMed: 36967224
DOI: 10.1177/14799731231166008 -
Expert Opinion on Drug Safety Mar 2023Respiratory depression and opioid-related death are reported when opioids are associated with gabapentinoids. Meta-analyses of randomized clinical trials investigating...
INTRODUCTION
Respiratory depression and opioid-related death are reported when opioids are associated with gabapentinoids. Meta-analyses of randomized clinical trials investigating efficacy and safety of such association failed to assess these risks because of the lack of data. The aim of this systematic review was to investigate the risk of respiratory depression or death during this combination in the scientific literature, including case reports or series, observational studies, and clinical trials.
AREAS COVERED
PubMed®, Web of Science®, Embase®, and Google Scholar® were searched from their inception to December 2021, for original articles in English, French, and German. Data synthesis was done on a narrative approach by type of articles.
EXPERT OPINION
The review included 25 articles (4 case reports, 2 cross-sectional, 3 case-control, 14 cohort studies, and 2 clinical trials). Respiratory depression or opioid-related death and co-exposure to gabapentinoids were associated in perioperative setting/chronic pain (odds ratios around 1.3) and in opioid maintenance treatment (hazard ratio 3.4). These findings are in agreement with experimental studies showing that a single dose of gabapentinoid may reverse opioid respiratory tolerance. Because the combination gabapentinoids-opioids is highly prevalent in all clinical context, all health care professionals and patients must be aware of this risk.
Topics: Humans; Analgesics, Opioid; Gabapentin; Cross-Sectional Studies; Respiratory Insufficiency; Pregabalin
PubMed: 36932941
DOI: 10.1080/14740338.2023.2193397 -
PloS One 2023Second-generation antipsychotics (SGAs) are frequently prescribed for the treatment of resistant anorexia nervosa. However, few clinical trials have been conducted so...
INTRODUCTION
Second-generation antipsychotics (SGAs) are frequently prescribed for the treatment of resistant anorexia nervosa. However, few clinical trials have been conducted so far and no pharmacological treatment has yet been approved by the Food and Drug Administration. The aim of this paper is to conduct a systematic scoping review exploring the effectiveness and safety of atypical antipsychotics in anorexia nervosa (AN).
METHOD
We conducted a systematic scoping review of the effectiveness and tolerability of SGAs in the management of AN. We included articles published from January 1, 2000, through September 12, 2022 from the PubMed and PsycInfo databases and a complementary manual search. We selected articles about adolescents and adults treated for AN by four SGAs (risperidone, quetiapine, aripiprazole or olanzapine). This work complies with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for scoping reviews (PRIMA-ScR) and was registered in the Open Science Framework (OSF) repository.
RESULTS
This review included 55 articles: 48 assessing the effectiveness of SGAs in AN and 7 focusing only on their tolerability and safety. Olanzapine is the treatment most frequently prescribed and studied with 7 randomized double-blind controlled trials. Other atypical antipsychotics have been evaluated much less often, such as aripiprazole (no randomized trials), quetiapine (two randomized controlled trials), and risperidone (one randomized controlled trial). These treatments are well tolerated with mild and transient adverse effects in this population at particular somatic risk.
DISCUSSION
Limitations prevent the studies both from reaching conclusive, reliable, robust, and reproducible results and from concluding whether or not SGAs are effective in anorexia nervosa. Nonetheless, they continue to be regularly prescribed in clinical practice. International guidelines suggest that olanzapine and aripiprazole can be interesting in severe or first-line resistant clinical situations.
Topics: Adult; Adolescent; Humans; Antipsychotic Agents; Olanzapine; Risperidone; Aripiprazole; Quetiapine Fumarate; Anorexia Nervosa; Benzodiazepines; Randomized Controlled Trials as Topic
PubMed: 36928656
DOI: 10.1371/journal.pone.0278189 -
Nutrients Jan 2023Although tremendous research has reported the protective effects of natural compounds in nonalcoholic fatty liver disease (NAFLD), there is still no approved drug. This... (Meta-Analysis)
Meta-Analysis Review
Although tremendous research has reported the protective effects of natural compounds in nonalcoholic fatty liver disease (NAFLD), there is still no approved drug. This study aimed to examine the efficacy of in NAFLD in preclinical studies. A total of 41 studies were identified by searching the PubMed, Web of Science, and Cochrane Library databases. The methodological quality was assessed by the risk of bias tool from the Systematic Review Center for Laboratory Animal Experimentation. The standardized mean difference (SMD) with a 95% confidence interval was calculated, and the random effects model was used to examine overall efficacy or heterogeneity. The publication bias was analyzed by Egger's test. The results showed that treatment significantly reduced the systemic levels of alanine aminotransferase (SMD: -2.15 IU/L; < 0.0001), aspartate aminotransferase (SMD: -2.86 IU/L; < 0.0001), triglyceride (SMD: -2.86 mg/dL; < 0.0001), total cholesterol (SMD: -1.69 mg/dL; < 0.0001), low-density lipoprotein (SMD: -1.46 mg/dL; < 0.0001), and fasting glucose (SMD: -1.45 mg/dL; < 0.0001) while increasing high-density lipoprotein (SMD: 1.22 mg/dL; = 0.0002) in NAFLD regardless of animal models or species. These findings may suggest that is a promising therapeutic agent for NAFLD treatment.
Topics: Animals; Non-alcoholic Fatty Liver Disease; Panax; Triglycerides; Lipoproteins, HDL; Lipoproteins, LDL
PubMed: 36771427
DOI: 10.3390/nu15030721 -
Expert Review of Anti-infective Therapy Mar 2023is included in the fungal infection category 'critical' by WHO because of associated high drug tolerance and spread at an alarming rate which if remains untouched may...
INTRODUCTION
is included in the fungal infection category 'critical' by WHO because of associated high drug tolerance and spread at an alarming rate which if remains untouched may result in serious outbreaks. Since its discovery in 2009, several assiduous efforts by mycologists across the world have deciphered its biology including growth physiology, drug tolerance, biofilm formation, etc. The differential response of various strains from different clades poses a hurdle in drawing a final conclusion.
AREAS COVERED
This review provides brief insights into the understanding of biofilm. It includes information on various models developed to understand the biofilms and conservation of different signaling pathways. Significant development has been made in the recent past with the generation of relevant in vivo and ex vivo models. The role of signaling pathways in the development of biofilm is largely unknown.
EXPERT OPINION
The selection of an appropriate model system is a must for the accuracy and reproducibility of results. The conservation of major signaling pathways in with respect to and highlights that initial inputs acquired from orthologs will be valuable in getting insights into the mechanism of biofilm formation and associated pathogenesis.
Topics: Humans; Candida; Candida auris; Reproducibility of Results; Saccharomyces cerevisiae; Biofilms; Candida albicans; Antifungal Agents
PubMed: 36755419
DOI: 10.1080/14787210.2023.2179036 -
Biomolecules Jan 2023A recent report showed that most pediatric cases of non-eosinophilic esophagitis (EoE) eosinophilic gastrointestinal disorders (EGIDs) (non-EoE EGIDs) are persistent and...
Dupilumab Leads to Clinical Improvements including the Acquisition of Tolerance to Causative Foods in Non-Eosinophilic Esophagitis Eosinophilic Gastrointestinal Disorders.
A recent report showed that most pediatric cases of non-eosinophilic esophagitis (EoE) eosinophilic gastrointestinal disorders (EGIDs) (non-EoE EGIDs) are persistent and severe compared with those of EoE, thus requiring further effective therapeutic approaches. In this study, we present the first case based on a systematic search of non-EoE EGID for which tolerance to causative foods and histological and symptomatic improvements were achieved following dupilumab administration, after elimination diets and omalizumab and mepolizumab treatments. Driven by this case, we investigated the efficacies of biological treatments in non-EoE EGID cases based on the patient studied herein, and other patients identified in the conducted systematic review. Seven articles, including five different biologics, were reviewed. Both clinical efficacies and impact differences among the targeted molecules are demonstrated in this study. Our findings show that dupilumab may affect mechanisms that can suppress symptoms induced by offending foods that are different from those induced by other biologics as identified in the conducted systematic review. Additional studies are required to address the unmet needs of non-EoE EGID treatments.
Topics: Child; Humans; Biological Products; Esophagitis; Treatment Outcome; Immune Tolerance
PubMed: 36671497
DOI: 10.3390/biom13010112