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Vaccines Jun 2024Kidney transplant recipients are at an increased risk of hospitalisation and death from SARS-CoV-2 infection, and standard two-dose vaccination schedules are typically...
Kidney transplant recipients are at an increased risk of hospitalisation and death from SARS-CoV-2 infection, and standard two-dose vaccination schedules are typically inadequate to generate protective immunity. Gut dysbiosis, which is common among kidney transplant recipients and known to effect systemic immunity, may be a contributing factor to a lack of vaccine immunogenicity in this at-risk cohort. The gut microbiota modulates vaccine responses, with the production of immunomodulatory short-chain fatty acids by bacteria such as associated with heightened vaccine responses in both observational and experimental studies. As SCFA-producing populations in the gut microbiota are enhanced by diets rich in non-digestible fibre, dietary supplementation with prebiotic fibre emerges as a potential adjuvant strategy to correct dysbiosis and improve vaccine-induced immunity. In a randomised, double-bind, placebo-controlled trial of 72 kidney transplant recipients, we found dietary supplementation with prebiotic inulin for 4 weeks before and after a third SARS-CoV2 mRNA vaccine to be feasible, tolerable, and safe. Inulin supplementation resulted in an increase in gut , as determined by 16S RNA sequencing, but did not increase in vitro neutralisation of live SARS-CoV-2 virus at 4 weeks following a third vaccination. Dietary fibre supplementation is a feasible strategy with the potential to enhance vaccine-induced immunity and warrants further investigation.
PubMed: 38932337
DOI: 10.3390/vaccines12060608 -
Pharmaceuticals (Basel, Switzerland) Jun 2024Complex regional pain syndrome (CRPS) is a disabling condition that usually affects the extremities after trauma or surgery. At present, there is no FDA-approved... (Review)
Review
Complex regional pain syndrome (CRPS) is a disabling condition that usually affects the extremities after trauma or surgery. At present, there is no FDA-approved pharmacological treatment for patients with CRPS. We performed this systematic review and meta-analysis to evaluate the efficacy and safety of pharmacological therapies and determine the best strategy for CRPS. We searched the databases, including PubMed, Embase, Cochrane, Web of Science, Scopus, and ClinicalTrials.gov, for published eligible randomized controlled trials (RCTs) comparing pharmacological treatment with placebo in CRPS patients. Target patients were diagnosed with CRPS according to Budapest Criteria in 2012 or the 1994 consensus-based IASP CRPS criteria. Finally, 23 RCTs comprising 1029 patients were included. We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to rate certainty (confidence in evidence and quality of evidence). Direct meta-analysis showed that using bisphosphonates (BPs) (mean difference [MD] -2.21, 95% CI -4.36--0.06, = 0.04, moderate certainty) or ketamine (mean difference [MD] -0.78, 95% CI -1.51--0.05, = 0.04, low certainty) could provide long-term (beyond one month) pain relief. However, there was no statistically significant difference in the efficacy of short-term pain relief. Ketamine (rank = 0.55) and BPs (rank = 0.61) appeared to be the best strategies for CRPS pain relief. Additionally, BPs (risk ratio [RR] = 1.86, 95% CI 1.34-2.57, 0.01, moderate certainty) and ketamine (risk ratio [RR] = 3.45, 95% CI 1.79-6.65, 0.01, moderate certainty) caused more adverse events, which were mild, and no special intervention was required. In summary, among pharmacological interventions, ketamine and bisphosphonate injection seemed to be the best treatment for CRPS without severe adverse events.
PubMed: 38931478
DOI: 10.3390/ph17060811 -
Pharmaceuticals (Basel, Switzerland) Jun 2024Ovarian cancer (OC) is a significant cause of cancer-related mortality in women globally, with a five-year survival rate of approximately 49%. Standard therapy involves... (Review)
Review
BACKGROUND
Ovarian cancer (OC) is a significant cause of cancer-related mortality in women globally, with a five-year survival rate of approximately 49%. Standard therapy involves cytoreductive surgery followed by chemotherapy. Its poor prognosis has driven interest in alternative therapies such as targeted molecular agents like bevacizumab and poly (ADP-ribose) polymerase inhibitors (PARPi).
MATERIALS AND METHODS
This review systematically searched PubMed from January 2018 to December 2023 for studies on PARPi in OC. Emphasis was on identifying relevant Phase III trials, extracting data on study design, patient demographics, and outcomes. Special focus was on assessing PARPi efficacy, safety, impact on quality of life, and ongoing trials, including those on Clinicaltrials.gov.
RESULTS
The efficacy of PARPi in first-line therapy for OC has been extensively studied. Trials like SOLO-1, PRIMA, and ATHENA-MONO have demonstrated significant improvements in progression-free survival (PFS) and overall survival (OS), particularly in patients with BRCA mutations. Additionally, the combination of PARPi with other agents like bevacizumab has shown promising results in extending PFS. However, PARPi treatment is associated with various adverse effects, including hematologic toxicities like anemia, thrombocytopenia, and neutropenia. While most adverse events are manageable, some patients may require dose adjustments or discontinuation of treatment. Importantly, PARPi maintenance therapy has not adversely affected health-related quality of life (HRQoL), with studies reporting similar HRQoL scores between PARPi-treated and placebo-treated patients.
CONCLUSIONS
PARPi offer effective treatment with manageable side effects, suitable even for medically fragile patients. Individualized dosing can optimize benefits while minimizing adverse events. Exploring diverse treatment approaches, particularly in patients with limited life expectancy or high disease burden, could improve outcomes. Ongoing research is investigating alternative therapies and combinations to broaden treatment options. Combining bevacizumab with PARPi may be justified for first-line and recurrent maintenance therapy. Regardless of mutational status, PARPi should be considered for maintenance therapy in newly diagnosed advanced OC. Platinum sensitivity remains crucial for treatment decisions and predicting survival outcomes.
PubMed: 38931448
DOI: 10.3390/ph17060778 -
Pharmaceuticals (Basel, Switzerland) Jun 2024In the New World, dogs are considered the main reservoir of visceral leishmaniasis (VL). Due to inefficacies in existing treatments and the lack of an efficient vaccine,...
Pharmacokinetics, Dose-Proportionality, and Tolerability of Intravenous Tanespimycin (17-AAG) in Single and Multiple Doses in Dogs: A Potential Novel Treatment for Canine Visceral Leishmaniasis.
In the New World, dogs are considered the main reservoir of visceral leishmaniasis (VL). Due to inefficacies in existing treatments and the lack of an efficient vaccine, dog culling is one of the main strategies used to control disease, making the development of new therapeutic interventions mandatory. We previously showed that Tanespimycin (17-AAG), a Hsp90 inhibitor, demonstrated potential for use in leishmaniasis treatment. The present study aimed to test the safety of 17-AAG in dogs by evaluating plasma pharmacokinetics, dose-proportionality, and the tolerability of 17-AAG in response to a dose-escalation protocol and multiple administrations at a single dose in healthy dogs. Two protocols were used: Study A: four dogs received variable intravenous (IV) doses (50, 100, 150, 200, or 250 mg/m) of 17-AAG or a placebo ( = 4/dose level), using a cross-over design with a 7-day "wash-out" period; Study B: nine dogs received three IV doses of 150 mg/m of 17-AAG administered at 48 h intervals. 17-AAG concentrations were determined by a validated high-performance liquid chromatographic (HPLC) method: linearity (R = 0.9964), intra-day precision with a coefficient of variation (CV) ≤ 8%, inter-day precision (CV ≤ 20%), and detection and quantification limits of 12.5 and 25 ng/mL, respectively. In Study A, 17-AAG was generally well tolerated. However, increased levels of liver enzymes-alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT)-and bloody diarrhea were observed in all four dogs receiving the highest dosage of 250 mg/m. After single doses of 17-AAG (50-250 mg/m), maximum plasma concentrations (Cmax) ranged between 1405 ± 686 and 9439 ± 991 ng/mL, and the area under the curve (AUC) plotting plasma concentration against time ranged between 1483 ± 694 and 11,902 ± 1962 AUC 0-8 h μg/mL × h, respectively. Cmax and AUC parameters were dose-proportionate between the 50 and 200 mg/m doses. Regarding Study B, 17-AAG was found to be well tolerated at multiple doses of 150 mg/m. Increased levels of liver enzymes-ALT (28.57 ± 4.29 to 173.33 ± 49.56 U/L), AST (27.85 ± 3.80 to 248.20 ± 85.80 U/L), and GGT (1.60 ± 0.06 to 12.70 ± 0.50 U/L)-and bloody diarrhea were observed in only 3/9 of these dogs. After the administration of multiple doses, Cmax and AUC 0-48 h were 5254 ± 2784 μg/mL and 6850 ± 469 μg/mL × h in plasma and 736 ± 294 μg/mL and 7382 ± 1357 μg/mL × h in tissue transudate, respectively. In conclusion, our results demonstrate the potential of 17-AAG in the treatment of CVL, using a regimen of three doses at 150 mg/m, since it presents the maintenance of high concentrations in subcutaneous interstitial fluid, low toxicity, and reversible hepatotoxicity.
PubMed: 38931434
DOI: 10.3390/ph17060767 -
Pharmaceuticals (Basel, Switzerland) Jun 2024The aim of this study is to evaluate the anti-HPV potential of a Lam seed, L. seed, and peel herbal mixture in the form of polymer film-forming systems. A clinical...
In Vitro and Randomized Controlled Clinical Study of Natural Constituents' Anti-HPV Potential for Treatment of Plantar Warts Supported with In Silico Studies and Network Analysis.
The aim of this study is to evaluate the anti-HPV potential of a Lam seed, L. seed, and peel herbal mixture in the form of polymer film-forming systems. A clinical trial conducted in outpatient clinics showed that the most significant outcome was wart size and quantity. Compared to the placebo group, the intervention group's size and number of warts were considerably better according to the results. Chemical profiling assisted by LC-HRMS led to the dereplication of 49 metabolites. Furthermore, network pharmacology was established for the mixture of three plants; each plant was studied separately to find out the annotated target genes, and then, we combined all annotated genes of all plants and filtered the genes to specify the genes related to human papilloma virus. In a backward step, the 24 configured genes related to HPV were used to specify only 30 compounds involved in HPV infection based on target genes. CA2 and EGFR were the top identified genes with 16 and 12 edges followed by PTGS2, CA9, and MMP9 genes with 11 edges each. A molecular docking study for the top active identified compounds of each species was conducted in the top target HPV genes, CA2 and EGFR, to investigate the mode of interaction between these compounds and the targets' active sites.
PubMed: 38931426
DOI: 10.3390/ph17060759 -
Pharmaceuticals (Basel, Switzerland) May 2024Public perception contrasts scientific findings on the depression-related effects of cannabis. However, earlier studies were performed when cannabis was predominantly... (Review)
Review
Public perception contrasts scientific findings on the depression-related effects of cannabis. However, earlier studies were performed when cannabis was predominantly illegal, its production was mostly uncontrolled, and the idea of medical cannabis was incipient only. We hypothesized that recent changes in attitudes and legislations may have favorably affected research. In addition, publication bias against cannabis may have also decreased. To investigate this hypothesis, we conducted a review of research studies published over the last three years. We found 156 relevant research articles. In most cross-sectional studies, depression was higher in those who consumed cannabis than in those who did not. An increase in cannabis consumption was typically followed by an increase in depression, whereas withdrawal from cannabis ameliorated depression in most cases. Although medical cannabis reduced depression in most studies, none of these were placebo-controlled. In clinical studies published in the same period, the placebo also ameliorated depression and, in addition, the average effect size of the placebo was larger than the average effect size of medical cannabis. We also investigated the plausibility of the antidepressant effects of cannabis by reviewing molecular and pharmacological studies. Taken together, the reviewed findings do not support the antidepressant effects of herbal cannabis.
PubMed: 38931356
DOI: 10.3390/ph17060689 -
Nutrients Jun 2024In the original publication [...].
Correction: Hill et al. A Multicenter, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of a Krill Oil, Astaxanthin, and Oral Hyaluronic Acid Complex on Joint Health in People with Mild Osteoarthritis. 2023, , 3769.
In the original publication [...].
PubMed: 38931329
DOI: 10.3390/nu16121961 -
Nutrients Jun 2024Sprout ginseng extract (ThinkGIN™) manufactured through a smart farm system has been shown to improve memory in preclinical studies. This study conducted a 12-week... (Randomized Controlled Trial)
Randomized Controlled Trial
Sprout ginseng extract (ThinkGIN™) manufactured through a smart farm system has been shown to improve memory in preclinical studies. This study conducted a 12-week randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of ThinkGIN™ for improving memory in subjective memory impairment (SMI). Subjects aged 55 to 75 years with SMI participated in this study. A total of 80 subjects who met the inclusion/exclusion criteria were assigned to the ThinkGIN™ group ( = 40, 450 mg ThinkGIN™/day) or a placebo group ( = 40). Efficacy and safety evaluations were conducted before intervention and at 12 weeks after intervention. As a result of 12 weeks of ThinkGIN™ intake, significant differences in SVLT, RCFT, MoCA-K, PSQI-K, and AChE were observed between the two groups. Safety evaluation (AEs, laboratory tests, vital signs, and electrocardiogram) revealed that ThinkGIN™ was safe with no clinically significant changes. Therefore, ThinkGIN™ has the potential to be used as a functional food to improve memory.
Topics: Humans; Panax; Double-Blind Method; Male; Plant Extracts; Middle Aged; Female; Aged; Memory Disorders; Treatment Outcome; Memory
PubMed: 38931306
DOI: 10.3390/nu16121952 -
Nutrients Jun 2024In recent years, there has been a notable surge in the popularity of beetroot-based dietary supplements, driven by their rich nitrate composition. Several types of... (Randomized Controlled Trial)
Randomized Controlled Trial
In recent years, there has been a notable surge in the popularity of beetroot-based dietary supplements, driven by their rich nitrate composition. Several types of beetroot-based dietary supplements can be found in markets worldwide; however, ensuring the safety of dietary supplements is a crucial consideration, as there is limited evidence on their safety, especially for older populations. Therefore, the purpose of the current study was to evaluate the safety and tolerability of a nitrate-rich beetroot extract in older participants taking supplements over 12 weeks. The participants were randomly assigned to receive 20 g daily of beetroot extract or a matching placebo. The safety and tolerability of the supplementation were evaluated as the occurrence of adverse events and anthropometric, biochemical, and hemodynamic parameters were measured. No serious adverse events were reported in any group. Anthropometric, biochemical, and hemodynamic parameter changes between the baseline and the end of the study were not statistically significant in either group. However, interestingly, the group receiving beetroot extract supplementation exhibited a notable increase in plasma nitrate levels ( = 0.076, = 0.50) and showed a decrease in insulin levels ( = 0.026, = 0.59). In conclusion, we found that 20 g of beetroot extract supplementation for 12 weeks was safe and well tolerated in older participants.
Topics: Humans; Dietary Supplements; Beta vulgaris; Plant Extracts; Aged; Male; Female; Nitrates; Plant Roots; Double-Blind Method; Insulin; Middle Aged
PubMed: 38931296
DOI: 10.3390/nu16121942 -
Nutrients Jun 2024The use of natural products as alternatives to traditional pharmacological treatments in orthodontics is gaining interest due to their anti-inflammatory, antibacterial,... (Review)
Review
The use of natural products as alternatives to traditional pharmacological treatments in orthodontics is gaining interest due to their anti-inflammatory, antibacterial, and antioxidant properties. This systematic review synthesizes evidence from clinical trials to evaluate the efficacy of natural products in reducing inflammation and bacterial presence in orthodontic and orthognathic treatment settings. The database search was conducted across PubMed, Scopus, and Embase up to January 2024. The review focused on randomized controlled trials only. The selected studies centered on the anti-inflammatory, antibacterial, and antioxidant effects of natural products, adhering to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines for data extraction. Nine studies, totaling 358 participants, were included. Significant findings demonstrated a reduction in gingival inflammation by over 40% with the use of Aloe vera compared to chlorhexidine. Another study noted a decrease in bleeding on probing by 13.6 points in the treatment group over placebo. Additionally, honey showed a rapid modulation of plaque pH and significantly reduced bacterial counts of . Furthermore, the use of resveratrol emulgel was linked to substantial improvements in gingival health, with a reduction in the gingival index and probing pocket depth. The results indicate that natural products can significantly enhance orthodontic treatment outcomes by reducing inflammation and bacterial levels. These products offer effective alternatives to traditional treatments and show potential for integration into routine orthodontic care protocols. Further research is encouraged to standardize application methods and dosages to maximize clinical benefits and patient satisfaction.
Topics: Humans; Aloe; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antioxidants; Biological Products; Chlorhexidine; Dentofacial Deformities; Gingivitis; Honey; Orthodontics; Plant Preparations; Randomized Controlled Trials as Topic; Resveratrol; Streptococcus mutans; Treatment Outcome
PubMed: 38931295
DOI: 10.3390/nu16121941