Current Reviews in Clinical and Experimental Pharmacology - Volume 19, Issue 1, 2024

Background: Ruta graveolens L. belongs to Rutaceae; it is a semi-wood perennial or a small evergreen sub-shrub, which is native to Southern Europe, West Asia and Northern Africa.

Objective: The goal of this manuscript was to outline the most notable traditional and modern advantages and pharmaceutical benefits of common rue.

Methods: The manuscript covers review articles, randomized control experiments, analytical studies and observations, which have been gathered from different sources, such as Google Scholar, Scopus, Science Direct and PubMed. A review of the literature was carried out using the keywords rutin, Ruta graveolens L., rue, common rune, coumarin, natural products and pharmaceutical benefits.

Results: Rue contains quinoline alkaloids, such as graveoline and graveolinine, acridone alkaloids, such as furacridone and gravacridone, furanoquinoline dictamnine, coumarins, such as gravelliferone, isorutarin, rutacultin, rutaretin, and suberenone, and the furanocoumarins 5-methoxypsoralen (bergapten) and 8-methoxypsoralen (xanthotoxine). Most of its aromatic and medicinal properties are due to the presence of rutin and its essential oil. It has been used in folk medicine as a stimulant, for its anti-inflammatory and analgesic properties, anti-androgenic activity, anti-hyperglycemic effects, anti-hyperlipidemic effects, xanthine oxidase inhibition activity, and anticancer properties.

Conclusion: According to pharmacological and phytochemical advantages, pennyroyal shows its importance as a medicinal plant in both modern medicinal science and traditional medicine.

Background: Since their inception, preclinical experimental models have played an important role in investigating and characterizing disease pathogenesis. These in vivo, ex vivo, and in vitro preclinical tests also aid in identifying targets, evaluating potential therapeutic drugs, and validating treatment protocols.

Introduction: Diarrhea is a leading cause of mortality and morbidity, particularly among children in developing countries, and it represents a huge health-care challenge on a global scale. Due to its chronic manifestations, alternative anti-diarrheal medications must be tested and developed because of the undesirable side effects of currently existing anti-diarrheal drugs.

Methods: Several online databases, including Science Direct, PubMed, Web of Science, Google Scholar and Scopus, were used in the literature search. The datasets were searched for entries of studies up to May, 2022.

Results: The exhaustive literature study provides a large number of in vivo, in vitro and ex vivo models, which have been used for evaluating the mechanism of the anti-diarrheal effect of drugs in chemically-, pathogen-, disease-induced animal models of diarrhea. The advances and challenges of each model were also addressed in this review.

Conclusion: This review encompasses diverse strategies for screening drugs with anti-diarrheal effects and covers a wide range of pathophysiological and molecular mechanisms linked to diarrhea, with a particular emphasis on the challenges of evaluating and predictively validating these experimental models in preclinical studies. This could also help researchers find a new medicine to treat diabetes more effectively and with fewer adverse effects.

Vaccines are important to improve immunity against pathogens and diseases. The current COVID-19 disease is rapidly evolving and spreading among people; therefore, it is important to utilize a proper vaccination strategy against it. Currently, many approved vaccines are available and accessible; however, there is a reported hesitancy against taking them among the public and even the health care workers. Mainly, this is attributed to the fear of the possible side effects and complications. Moreover, inaccurate knowledge disseminated through the media/social media especially by those who lack the proper expertise, adds confusion and more fear that affects the vaccination decision. For such reasons, it is essential to find strategies to increase the acceptability of vaccines and enhance confidence in the vaccination process. This should be accompanied by sufficient efforts and proper clinical studies to confirm the value and the safety of the vaccines. Those strategies are important to avoid the further spread of the COVID-19 disease and abort the pandemic worldwide, especially when considering the likely approach towards a COVID-19 booster vaccination program, in which booster vaccines are re-taken along intervals to adequately contain the rapidly evolving nature of the virus. This review article highlights the factors influencing the acceptability of the COVID-19 vaccination and enrollment in clinical trials among the public and some specific populations. Furthermore, it summarizes the suggested strategies and recommendations to improve attitudes towards COVID-19 vaccination programs.

Background: Dental implants have been one of the most popular treatments for rehabilitating individuals with single missing teeth or fully edentulous jaws since their introduction. As more implant patients are well-aged and take several medications due to various systemic conditions, clinicians should take into consideration the possible drug implications on bone remodeling and osseointegration.

Objective: The present study aims to examine and review some desirable and unwelcomed implications of medicine on osseointegration.

Methods: A broad search for proper relevant studies was conducted in four databases, including Web of Science, Pubmed, Scopus, and Google Scholar.

Results: Some commonly prescribed medicines, such as nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, proton pump inhibitors (PPIs), selective serotonin reuptake inhibitors (SSRIs), anticoagulants, metformin, and chemotherapeutic agents, may jeopardize osseointegration. On the contrary, some therapeutic agents, such as anabolic, anti-catabolic, or dual anabolic agents may enhance osseointegration and increase the treatment’s success rate.

Conclusion: Systemic medications that enhance osseointegration include mineralization promoters and bone resorption inhibitors. On the other hand, medications often given to the elderly with systemic problems might interfere with osseointegration, leading to implant failure. However, to validate the research, more human studies with a higher level of evidence are required.

Opioids administered into the spinal space by intrathecal or epidural routes can provide potent and prolonged selective analgesia. Compared to the systemic administration of opioids, spinal administration can bring about analgesia with fewer central and systemic adverse effects. For the past 40 years, spinal opioid analgesia has achieved great popularity in various fields of pain treatment. The aim of this work is to identify clinical studies that initiated the use of spinal opioids for the treatment of pain.

To determine the historical role of each of the review’s studies, we used the combination of two factors: the study priority in terms of the time of its publication and the degree of its acknowledgement in the form of citation impact. The date of publication was regarded as the primary factor, but only if the count of citations indicated a sufficient acknowledgement by the other authors. The citation impact was assessed as the initial citation count – for a period of five years after the year of article publication – and the total count.

Analysis of the related data shows that the clinical studies initiating the use of spinal opioids for the treatment of pain belong to two groups of authors – Wang et al. and Behar et al. Both studies were published in 1979 and described delivery of morphine into the spinal space, although the techniques of administration were different: Wang et al. injected morphine intrathecally, Behar et al. administered morphine epidurally. The response to these studies was overwhelming - close to a dozen reports on this topic were published in 1979 and more than a hundred – in 1980-1981. The total citation response to the Wang et al. article reached 699, and that to Behar et al. – 518. Two earlier records (1900-1901) of the use of intrathecal morphine, by Nicolae Racoviceanu-Pitesti and Otojiro Kitagawa, found no following in medical literature for more than three quarters of a century.

Background: Acanthamoeba is one of the opportunistic parasites with a global prevalence. Currently, due to the side effects and the emergence of drug resistance to this parasite, much research has been performed on the use of nano-drugs to treat Acanthamoeba-caused diseases. Therefore, this systematic review study aims to evaluate new strategies for treating diseases caused by Acanthamoeba based on nanoparticles (NPs).

Methods: We designed a systematic review based on the articles published in English between 2000 and 2022. Our search strategy was based on syntax and specific tags for each database, including ScienceDirect, PubMed, Scopus, Ovid, and Cochrane. From the articles, those that had inclusion criteria were selected, and their data were extracted and analyzed.

Results: In this study, 26 studies were selected. Metallic nanoparticles were mostly used against the Acanthamoeba species (80.7%). 19.2% of the studies used polymeric nanoparticles, and 3.8% used emulsion nanoparticles. Most studies (96.1%) were performed in vitro, and only one study (3.8%) was carried out in vivo. Silver NPs were the most used metallic nanoparticles in the studies. The best effect of the anti-Acanthamoeba compound was observed for green synthesized nanoparticles based on stabilization by plant gums, loaded with citrus fruits flavonoids hesperidin (HDN) and naringin (NRG) with a 100% growth inhibition at a concentration of 50 μg/mL.

Conclusion: This study showed that chlorhexidine and other plant metabolites loaded with silver and gold nanoparticles increase the anti-Acanthambae activity of these nanoparticles. However, green synthesized nanoparticles based on stabilization by plant gums, loaded with citrus fruits flavonoids hesperidin (HDN) and naringin (NRG), showed the best anti-Acanthambae effect. Nevertheless, further studies should be performed to determine their safety for human use.

Background: Many medications have different pharmacokinetics in children than in adults. Knowledge about the safety and efficacy of medications in children requires research into the pharmacokinetic profiles of children's medicines. By analysing registered clinical trial records, this study determined how frequently pharmacokinetic data is gathered in paediatric drug trials.

Methods: We searched for the pharmacokinetic data from clinical trial records for preterm infants and children up to the age of 16 from January 2011 to April 2022. The records of trials involving one or more drugs in preterm infants and children up to the age of 16 were examined for evidence that pharmacokinetic data would be collected.

Results: In a total of 1483 records of interventional clinical trials, 136 (9.17%) pharmacokinetic data involved adults. Of those 136 records, 60 (44.1%) records were pharmacokinetics trials involving one or more medicines in children up to the age of 16.20 (33.3%) in America, followed by 19 (31.6%) in Europe. Most trials researched medicines in the field of infection or parasitic diseases 20 (33.3%). 27 (48.2%) and 26 (46.4%) trials investigated medicines that were indicated as essential medicine.

Conclusion: The pharmacokinetic characteristics of children's drugs need to be better understood. The current state of pharmacokinetic research appears to address the knowledge gap in this area adequately. Despite slow progress, paediatric clinical trials have experienced a renaissance as the significance of paediatric trials has gained international attention. The outcome of paediatric trials will have an impact on children's health in the future. In recent years, the need for greater availability and access to safe child-size pharmaceuticals has received a lot of attention.

Objective: To determine the efficacy of the first triple CFTR protein modulators in children and adolescents with cystic fibrosis.

Methods: Systematic review and meta-analysis were conducted, following PRISMA guidelines. The following databases were searched extensively: PubMed/Medline, Clinical trials.gov, Google Scholar, Scopus, Embase, and Europe PMC using the keywords: “Ivacaftor”, “Elexacaftor”, “Tezacaftor”, VX_661”, VX_770”, “VX_445”, “cystic fibrosis”. A total of ten randomized clinical trials were included in our analysis. Primary outcomes included: Absolute change in predicted FEV1 from baseline, Absolute change in sweat chloride test from baseline, Absolute change in BMI from baseline, Absolute change in CF-QR from baseline, and Adverse Events.

Results: Among primary findings, significant absolute change in predictive FEV1 from baseline through 4 weeks favoured the triple CFTR protein modulators. (MD = 11.80, 95% CI = 8.47_15.12, p value = <0.00001); as well as CF_QR score (MD = 0.00, 95% CI = -2.50_2.50, p value= 1.00), and BMI kg/m² change (MD = 16.90, 95% CI = 12.73_21.06, p value= <0.00001). No significant change was noted for CFTR channels activity in the treatment group when compared to placebo or VX_770/VX_661 (MD = -12.57, 95% CI = -94.46_69.32, p value= 0.76).

Conclusion: In children aged ≥ 6 y old and adolescents with F508del_CFTR mutation, Elexacaftor-Tezacaftor-Ivacaftor tend to be more effective than first-generation therapy, demonstrating promising results by exhibiting significant improvement in lung function, body weight, and respiratory-related quality of life.

Background: Urinary tract infections (UTIs) are the most prevalent bacterial infections that occur in children worldwide.

Objective: This meta-analysis aims to investigate the utility of probiotics as preventive therapy in children with a UTI.

Methods: The Web of Science, PubMed, and Scopus were searched for articles that investigated the relationship between probiotic consumption and the risk of UTIs. The quality of the articles was evaluated using the Jadad scale. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effects model. Subgroup analyses and sensitivity analyses were also conducted. The Cochran Q test and the statistic I² were used to evaluate heterogeneity. To determine any potential publication bias, the Egger’s and Begg’s tests were used.

Results: In total, eleven studies were selected for the systematic review and meta-analysis. Compared to children who did not receive probiotics, the OR of developing or having a recurring urinary tract infection in those who received probiotics was 0.94 (95% CI; 0.88–0.999; p-value=0.046). The Begg's and Egger's tests showed no evidence of publication bias between probiotics and the risk of developing new or recurring urinary tract infections.

Conclusion: Based on this systematic review and meta-analysis, probiotics could be an alternative therapy for children who are at risk of developing a UTI. They are non-pharmaceutical options and could be used as natural prophylaxis for UTIs. However, the currently published evidence does not irrefutably confirm that probiotics provide a protective effect against urinary bacterial infections. Therefore, there need to be large-scale randomized clinical trials undertaken to investigate the possible prophylaxis of probiotics.