Anti-seizure Effects and Mechanisms of Berberine: A Systematic Review.

BACKGROUND: Epilepsy is one of the most common in all age groups and disabling neurologic disorders around the world. OBJECTIVES: This systematic review was to explore whether berberine (BBR) has any anti-seizure or anti-epileptic effects and also reviewed this possible mechanism. METHODS: The EMBASE, Scopus, Cochrane Library, PubMed, and Web of Science databases were searched before Sep 2023. All types of studies that investigated the effects of BBR on epilepsy or chemical-induced seizures were eligible for inclusion. Two authors independently evaluated and reviewed titles/abstracts to identify publications for potential eligibility, and a third team member resolved discrepancies. Data were extracted in an Excel form, and the outcomes were discussed. RESULTS: BBR showed its neuroprotective properties by reducing oxidative stress, neuroinflammation, and anti-apoptosis effects. It also increases brain-derived neurotrophic factor (BDNF) release and reduces transforming growth factor-beta (TGF-ß1) and hypoxia-inducible factor 1α (HIF-1α). BBR by increasing scavenging reactive oxygen species (ROS), nuclear factor erythroid 2-related factor 2 (Nrf2), endogenous antioxidant enzymes, heme oxygenase-1 (HO-1), and inhibition of lipid peroxidation insert its antioxidant activity. Moreover, BBR showed antiinflammatory activity by reducing Interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha (TNF-α) levels and through inhibiting cyclooxygenase-2 (COX-2), and including nuclear factor κB (NF-κB). In addition, it modulated c-fos expression and neuronal excitability in the brain. CONCLUSION: BBR indicated promising anti-seizure effects with remarkable antioxidant, antiinflammatory, anti-apoptotic, and neuroprotective activity. Future studies should be based on well-designed clinical trial studies that are integrated with new methods related to increasing bioavailability.

The Association between Use of Renin-Angiotensin-Aldosterone System Inhibitors and the Risk and Mortality of Pancreatic Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Pancreatic Cancer (PC) is one of the most malignant tumors and highly invasive neoplasms around the world. OBJECTIVE: This systematic review and meta-analysis aims to study the relationship between the use of renin-angiotensin-aldosterone system inhibitors and the incidence and mortality of PC. METHODS: The electronic search was conducted systematically until October 10, 2023. in databases, including Scopus, Web of Science (WOS), PubMed/MEDLINE, Cochrane Library, and Embase. The required data were extracted from the articles and were analyzed by Stata 15 using statistical tests (Chi-square and I2), Forest plots, and publication bias tests (Begg's and Egger's tests). RESULTS: A total of four studies (2011-2019; n=314,856) investigated the relationship between RAS antagonists and PC risk. No significant associations were found between angiotensin receptor blockers (ARBs) (OR=0.94, 95% CI: 0.77-1.14, p=0.513), angiotensin-converting enzyme inhibitors (ACEIs) (OR=0.96, 95% CI: 0.84-1.09, p=0.505), or combination therapy (ARBs + ACEIs) (OR=0.97, 95% CI: 0.87-1.09, p=0.627) and PC risk. Also, nine studies (2010-2023; n=20,483) examined the association between renin-angiotensin-aldosterone system inhibitors and PC mortality. Significant reductions in PC mortality were found for ARBs (OR=0.81, 95% CI: 0.66-0.98, p=0.032), ACEIs (OR=0.89, 95% CI: 0.80-0.99, p=0.038), and combination therapy (OR=0.83, 95% CI: 0.70-0.97, p=0.022). No evidence of publication bias was found in the study results. CONCLUSION: In summary, while renin-angiotensin-aldosterone system inhibitors did not appear to impact PC risk, their use was associated with lower PC mortality based on this meta-analysis of the current evidence. More rigorous and well-designed studies are required to validate and support these findings.

Obesity and the Risk of Developing Kidney Stones: A Systematic Review and Meta-analysis.

Obesity is a growing problem that causes various metabolic disorders and organ dysfunction. The present systematic review and meta-analysis examined the impact of obesity on the risk of kidney stones. This meta-analysis was designed according to PRISMA guidelines. This extensive search was conducted on June 6, 2022, using relevant keywords in databases including PubMed, Web of Science, EMBASE, and Scopus. The data collected from observational studies were recorded in a datasheet. Odds Ratio (OR) and their 95% confidence intervals (CI) evaluated the overall effect size. The Cochran Q test and the statistic I2 were used to evaluate the heterogeneity of studies. Egger's and Begg's tests assessed potential publication bias. We included 15 observational studies published between 2005 to 2022 in this analysis. Compared to nonobese individuals, the OR for developing kidney stones in obese participants was 1.35 (95% CI: 1.20 to 1.52, P < .001). Considering geographical location, the OR for the risk of developing kidney stones in obese individuals was 1.51 (95% CI: 1.11 to 2.05, P = .009) in North America, 1.33 (95% CI: 1.16 to 1.51, P < .001) in Europe, and 1.18 (95% CI: 1.08 to 1.29, P < .001) in Asia. Begg's test results (P = .625) demonstrated no publication bias. However, Egger's test results (P = .005) indicated publication bias. Based on the results, obesity increases the risk of kidney stone development. Therefore, community health programs should be implemented to reduce the incidence of obesity and lower the risk of kidney stones.  DOI: 10.52547/ijkd.7223.

A Systematic Review and Meta-analysis on the Role of Statins in the Prevention of Mortality Following Pancreatic Cancer.

BACKGROUND: Pancreatic cancer (PC) is a type of cancer with a high incidence and case-fatality rate. OBJECTIVE: This study aimed to evaluate the role of statins in preventing mortality following PC based on scientific evidence with systematic review and meta-analysis method. METHODS: This meta-analysis considered studies published from 1980 till the end of 2022 in ISI Web of Science, Scopus, PubMed, Cochrane, Science Direct, Google Scholar, and Embase databases. Funnel diagrams and Begg's and Egger's tests were used to assess the publication bias. RESULTS: In general, this meta-analysis has included 19 studies (13 cohort studies, 4 case-control, and 2 randomized clinical trials (RCTs)) and a total of 100,888 patients with PC. The risk of mortality of PC in statin users in total was 0.86 (95% CI: 0.80 - 0.92, P-value <0.001); in the case-control studies, it was equal to 0.53 (0.34-0.83); in the cohort studies, it was equal to 0.87 (0.82-0.92, P-value <0.001); in RCTs, it was equal to 1.19 (0.99-1.42, P-value <0.001); in studies with good quality score category, it was equal to 0.92 (0.86-0.99, P-value <0.001), and in articles of the moderate quality score category, it was equal to 0.73 (0.64-0.84, P-value <0.001). The results of statistical tests indicated the existence of publication bias (Begg's test (P-value = 0.002) and Egger's test (P-value = 0.004)). CONCLUSION: Statins reduce the risk of mortality in patients with PC. However, no significant relation has been observed in RCTs. Therefore, it is necessary to be cautious in interpreting the results.

The Association between Statins Intake and Risk of Post Stroke Pneumonia: A Systematic Review and Meta-analysis.

AIM: This research aimed to examine the relationship between the intake of statins and the risk of post-stroke pneumonia in a systematic review and meta-analysis study. METHODS: An extensive search of published articles on March 21st , 2023, was done in several databases, like Web of Science (ISI), PubMed, Cochrane Library, Embase, Scopus, and Google Scholar. The Newcastle Ottawa Scale (NOS) checklist was employed to evaluate the quality of observational studies. Statistical tests (Chi-square test and I2 ) and graphical techniques (Forest plot) were used to determine whether heterogeneity existed in the meta-analysis studies. Funnel plots and Begg and Egger's tests were used to assess the publication bias. RESULTS: Seven studies (5 cohort and 2 case-control studies) were retrieved to examine the association between statins and post-stroke pneumonia. The sample size of the studies compiled in the meta-analysis was obtained to be 68,966 participants. Meta-analysis demonstrated that the overall odds of post-stroke pneumonia in the statin group was equal to 0.87 (95% CI: 0.67 - 1.13; p-value 0.458). Subgroup analysis indicated that the odds of post-stroke pneumonia in the statin group was equal to 0.93 (95% CI: 0.73-1.18; p-value=0.558) in the cohort studies, and equal to 0.92 (95% CI: 0.37-2.26; p-value=0.857) in the case-control studies. The examination of the association between the intake of statins and post-stroke pneumonia showed no evidence of publication bias (Begg's test, p-value = 0.368; Eggers test, p-value = 0.282). CONCLUSION: In this study, no relationship has been observed between receiving statins and the risk of post-stroke pneumonia.

The Role of Vitamin D in Carpal Tunnel Syndrome Risk and Supplementation Outcomes: A Systematic Review.

BACKGROUND: Carpal tunnel syndrome (CTS) is a debilitating neuropathy that accompanies pain and other physical limitations and disrupts the normal functioning of the victims' lives. OBJECTIVE: We aimed to investigate Vitamin D's preventive and therapeutic effects on the occurrence and remission of CTS symptoms. METHODS: In this systematic review the PRISMA statement has been designed primarily. An extensive search was undertaken in various databases, including PubMed, Cochrane library, Web of Science, EMBASE, and Scopus. After considering the inclusion and exclusion criteria of the study, finally, 19 articles were retrieved. The raw data were extracted and entered into an Excel form, and the study outcomes were investigated. RESULTS: The main symptoms and tests, including functional score, nerve conduction, and pain, were improved after Vitamin D supplementation in CTS patients. However, they revealed worse scores in people with low Vitamin D levels. In addition, the scores of mentioned indices were worsened in people with lower serum Vitamin D levels. Nevertheless, some studies did not find a significant relationship between low serum 25(OH)D and more significant pain scores in CTS patients. In addition, Vitamin D inserts its effects on CTS by regulating cell proliferation, nerve growth factor, suppression of oxidative stress and inflammatory cytokines, and improvement in cartilage and microvascular damage. CONCLUSION: Vitamin D supplementation can improve the symptoms in CTS patients, and low serum 25(OH)D can aggravate the symptoms of the disease and could be a risk factor for its occurrence. However, more observational studies and clinical trials are needed.

Anti-inflammatory response to curcumin supplementation in chronic kidney disease and hemodialysis patients: A systematic review and meta-analysis.

Objective: This study was designed to determine the association curcumin has on pro-inflammatory biomarkers in patients with chronic kidney disease (CKD (and in those receiving hemodialysis (HD). Materials and Methods: This meta-analysis was undertaken following PRISMA guidelines. An extensive systematic review was undertaken until 10/11/2021 using PubMed, Web of Science (ISI), and Scopus databases. The standardized mean difference (SMD) and 95% confidence intervals (CI) were used to estimate the overall effect size of curcumin on serum high-sensitivity C-reactive protein (hs-CRP), and pro-inflammatory cytokines including interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) in patients with CKD and those receiving HD. Results: Overall, ten randomized controlled trials (RCTs) comprising 523 patients were incorporated into the systematic review and meta-analysis. The results showed that when compared with control groups, there was no significant effect observed linking curcumin and IL-6 (SMD = 0.24%, 95% CI = -0.14 to 0.62, p = 0.221), TNF-α (SMD = 0.11%, 95% CI = -0.19 to 0.40, p = 0.480) or hs-CRP (SMD = -0.17%, 95% CI = -0.36 to 0.03, p = 0.093). The analysis determined no publication bias related to the influence of curcumin on IL-6, TNF-α or acute phase reactant, hs-CRP. The Egger's and Begg's test results were not statistically significant (p˃0.20). Conclusion: In patients with CKD and those receiving HD, the use of curcumin supplementation has no statistically significant effect on the anti-inflammatory biomarkers reviewed in this study.

Herbal medicines: challenges in the modern world. Part 1. Australia and New Zealand.

As in many developed countries, herbal medicines (HMs) are widely used in Australia and New Zealand (NZ). The popularity of HM continues to rise. Western, Asian and indigenous HMs are used, reflecting the cultural diversity of people in this region. HMs in Australia are regulated on a risk-based system with many HMs identified as being low risk. The legislation was reviewed in 2015 and proposals for change are under consideration. In NZ, it is recognised that current regulations for HMs and other natural health products (NHPs) do not adequately protect public health. NZ is entering a phase of regulatory change for this sector, and proposals for a 'light-touch' regulatory framework for NHPs are planned to be introduced into legislation during 2016.

Herbal medicines: challenges in the modern world. Part 3. China and Japan.

INTRODUCTION: Medicinal plants, and formulations prepared from them, have been used in China and Japan for thousands of years. Nowadays, ancient formulations of Traditional Chinese and Kampo (Japanese) Medicines coexist with Western herbal medicines (HMs) and complement each other. HMs are used for the treatment of mild and chronic diseases, as an adjunct therapy, to improve wellbeing and delay aging, or as healthy (functional) foods. AREAS COVERED: This article, a third part in a series of reviews, is focusing on history, use and regulation of the traditional and modern HMs in Japan and China. Materials available from legislative and governmental websites, PubMed and news media were used. Expert commentary: HMs are heavily regulated in both countries, often in a similar manner as conventional pharmaceutical drugs. The majority of herbal formulations are sold as over-the-counter medications supplied with leaflets describing indications and appropriate dosages for patients of different ages. Medical practitioners prescribe herbal formulations that are tailored to the needs of particular patients. Both countries had problems with adverse drug reactions and toxicity of single herbs and herbal formulations that have been investigated by authorities, and some drugs have been removed from the market.

Herbal medicines: challenges in the modern world. Part 2. European Union and Russia.

INTRODUCTION: Herbal medicines (HMs) have been well known to people of the European Union (EU) and Russia for centuries. Currently, Western HMs can be classified into two categories, plant-derived conventional medicines and dietary supplements. Interest to HMs has grown rapidly in all countries during the past two decades. AREAS COVERED: The main goal of this review article is to present the history of HMs in the EU and Russia, forms of modern HMs, including Oriental Medicines that are popular among consumers of both countries. Additional discussion points comprise safety and adulteration issues associated with HMs, including regulatory changes and new legislative measures undertaken by the authorities. Materials available from legislative and governmental websites, PubMed and news media were used. Expert commentary: Due to cultural diversities in the EU and Russia, traditional HMs of other regions, particularly Chinese Traditional and Ayurvedic medicines, are also popular. Recently, dietary supplements containing multiple herbal and other natural products have flooded the EU and Russian markets. Pharmacovigilance in these markets is challenging in terms of establishing quality and safety of ingredients, determining efficacy, and defining risks of herb-herb and herb-drug interactions. Both the EU and Russia have introduced new legislation aimed to overcome these deficiencies.

Clinical pharmacokinetics and pharmacodynamics of ganciclovir and valganciclovir in children with cytomegalovirus infection.

INTRODUCTION: Among infants and immunocompromised children cytomegalovirus (CMV) is associated with significant morbidity and mortality. AREAS COVERED: This review describes the clinical pharmacokinetics and pharmacodynamics of ganciclovir and valganciclovir for the treatment and prevention of CMV infection in children. EXPERT OPINION: A 24-h ganciclovir area under the concentration versus time curve (AUC0₋24) of 40 - 60 µg h/ml decreased the risk of CMV infection for adults undergoing CMV prophylaxis. For adults undergoing treatment for active CMV disease, a target AUC0₋12 of 40 - 60 µg h/ml has been suggested. The applicability of these targets to children remains uncertain; however, with the most sophisticated dosing regimens developed to date only 21% of patients are predicted to reach these targets. Moving forward, identification of optimal pediatric ganciclovir and valganciclovir dosing regimens may involve the use of an externally validated pediatric population pharmacokinetic model for empirical dosing, an optimal sampling strategy for collecting a minimal number of blood samples for each patient and Bayesian updating of the dosing regimen based on an individual patient's pharmacokinetic profile.

Bioequivalence and Bioavailability Clinical Trials: A Status Report from the National Institutes of Health ClinicalTrials.gov Registry.

Drug development is an expensive process that is marked by a high-failure rate. For this reason early stage bioequivalence and pharmacokinetic studies are essential in determining the fate of new drug products. In this study, we sought to systematically assess the current trends of ongoing and recently completed bioequivalence and bioavailability trials that have been registered within a national clinical trials registry. All bioequivalence and bioavailability studies registered in the United States ClinicalTrials.gov registry from late-2007 through 2011 were identified. Over this period, more than 2300 interventional bioequivalence and bioavailability trials were registered. As of 2013, the vast majority of studies (86%) have been completed, 10% are actively recruiting participants, and the remainder are engaged in data analysis (4%). When compared to completed trials, ongoing trials are in later phases of clinical development, recruiting larger numbers of participants, and more likely to recruit women and children (P<0.001 for all). These data suggest that the quality of bioequivalence and bioavailability studies has improved rapidly, even over the last five years. However, further work is needed to sustain - and accelerate - these improvements in the design of bioequivalence and bioavailability studies to ensure that safe and efficacious medicines swiftly reach healthcare providers and their patients.

Metabolic and toxicological considerations for sepsis drug treatments.

INTRODUCTION: Sepsis, a complex interaction between pathogen and host response, presents a difficult challenge for clinicians and researchers alike. With an increasing understanding of the pathophysiology of the disease, new treatment paradigms are evolving. AREAS COVERED: This article reviews the metabolic and toxicological considerations in sepsis, including the unique issues involved in neonatal and pediatric populations that differentiate it from adult sepsis. The authors cover metabolic issues, such as perfusion, renal and hepatic dysfunction and fluid retention in conjunction with their impact on therapy. Furthermore, the authors examine toxicological considerations of nephrotoxicity, ototoxicity and adverse drug reactions. The authors also present novel biomarkers of sepsis and current clinical tests utilized for the diagnosis of sepsis, as well as the limitations in animal models of sepsis and newer therapies. An extensive literature search including relevant formulae, publications and textbooks serves as the basis for this review. EXPERT OPINION: Improving understanding of the metabolic and toxicological issues in sepsis will allow the development of more effective multifaceted treatments and reduction of risks. Clinical research will need to more heavily involve neonatal and pediatric patients given the number of individuals who die from sepsis within these special populations. Development of a sepsis-specific inflammatory biomarker would allow more rapid detection as well as a method to determine the effectiveness of novel therapies.