Safety Of Medicines Research Articles

Consumer views on the use of digital tools for reporting adverse drug reactions: a cross-sectional study.

The application of digital technologies has shown benefits in enhancing pharmacovigilance activities but consumers views on the use of these tools for this purpose are not well described. To explore consumers' views on using digital tools to report adverse drug reactions (ADRs) and identify key features that consumers want in digital tools for ADR reporting. An online survey was conducted among adults who had taken medicine in the previous six-months in Australia. The development of questions was guided by the Combined Technology Acceptance Model and Theory of Planned Behaviour (C-TAM-TPB) framework. Responses to closed-ended questions were analysed using descriptive statistics and chi-square/Fisher's exact test, while free-text responses were analysed using qualitative content analysis. A total of 494 responses were included in the analysis. Eighty-seven percent of respondents preferred using digital tools for reporting ADRs. Consumers indicated a free-text space for describing ADRs (90%) as important or very important features of digital tools for ADR reporting, followed by acknowledgement of their report submission (87%) and receiving summary of previously reported ADRs (87%). Women (p < 0.001), advanced smartphone users (p < 0.001), and previous digital healthcare tool users (p = 0.017) showed higher intention to use digital tools. Consumers emphasized the importance of ease-of-use, accessibility, receiving medicine safety information, feedback, and advice for reporting ADRs via digital tools. Consumers prefer using digital tools for reporting ADRs and place high value on features such as a free-text space for describing ADRs, acknowledgement of report submissions, and access to summaries of previously submitted reports.

Pharmacovigilance in Australia – how do adverse event reports from clinicians contribute to medicine and vaccine safety?

Pharmacovigilance in Australia – how do adverse event reports from clinicians contribute to medicine and vaccine safety?

Drug safety: an integrated approach

Drug safety is a system of established principles and practical recommendations aimed at ensuring the safe and effective use of medicines. The aim of the study was to develop principles and design a conceptual model of drug safety based on a systematic analysis and an integrated approach. Material and methods. Systematic analysis of literary and Internet sources, a systematic approach, logical analysis, graphical method, modeling. Based on the study of the specifics of the existing pharmaceutical market and its participants, the regulatory framework, literary and Internet sources characterizing the circulation of medicines, drug-related problems of patient treatment, ethical norms and rules and system analysis, the principles of drug safety are proposed. The concept of drug safety is considered as a three-dimensional phenomenon requiring an integrated approach. Taking into account the system analysis, a conceptual model of drug safety has been developed, which includes 6 key elements: ensuring the safety of medicines from the state, manufacturers of medicines, medical and pharmaceutical workers, patients, the need for support and training of specialists, as well as directions for their implementation. The external factors influencing the clinical effectiveness of drugs and improving the quality of work of medical and pharmaceutical specialists are shown.

Using the Work Ability Index (WAI) to assess the possibility of returning to the profession after treatment

The use of the index of working capacity in medicine and occupational safety makes it possible to assess the individual working capacity of workers, to predict the possibility of retaining workers in the profession. A survey using the ability to work index helps to identify personnel who have an increased risk of dismissal and absence from work related to health and poor work results. Various pathological conditions can take an employee out of work for different periods, but it is extremely important to understand whether it is possible to preserve the employee's specialty and the prospects for his socialization. The disease changes not only the physical, but also the psycho-emotional state of the employee. The authors presented an analysis of modern scientific literature on the international experience of using the ability to work index to predict the possibility of returning to work in the specialty after treatment of diseases, rehabilitation. The work ability index can be used as a criterion for the effectiveness of treatment and rehabilitation after illness and subsequent employment. The link between quality of life and returning to work is of great importance. The ability to work of employees with various diseases, who have received different types of treatment, including surgical interventions, chemoradiotherapy and returned to work, is reduced compared with healthy employees. Recovery depends on the stage of the disease, the type of treatment and concomitant pathology. The risk of early retirement increases in the first years after cancer treatment. Professional rehabilitation promotes the fullest integration of an employee into society through professional self-realization.

Tackling the Burden of Substandard and Falsified Medicines and Health Technologies in Somaliland and Somalia

Background: The problem posed by the substandard and falsified (SF) medicines is a rising global challenge. WHO estimates that sales of SF medical products in low- and middle-income countries is around US$ 30 billion whereby 1 in 10 medical is substandard or falsified. Objectives: The purpose of this article was to enlighten the actions by the Somali NRA to tackle the scourge of SF medicines in Somalia. Methods: The literature was reviewed on the topic and evidence from other sources were incorporated including reports of post-marketing surveillance surveys, assessments at national and regional levels, as well as author’s experiences. Findings: The medicines regulatory capacity is weak in Somaliland and Somalia, where only 16% of total indicators for the regulatory system was in place as per WHO/IGAD rapid benchmarking of the National Regulatory Authority (NRA) in 2017, increasing the risk of circulation of SF medicines in the local private sector dominated and exclusively import relied pharmaceutical supply chain. Key actions by the NRA to address this problem include: regulatory reliance mechanisms such as using the WHO PQ/EUL for emergency authorization of vaccines, i.e. COVID-19 vaccines, enhanced licensing procedures, information exchange with NRAs in the region as well as technical collaboration with WHO. Conclusion &amp; Recommendation: However, a lot has to be done and considering the weak laboratory capacity and the porous national borders, the risk of local circulation of SF medicines is high and swift actions are needed to ensure access to safe and quality medicines and health technologies in Somaliland and Somalia.

Contribution of Ayurveda to achieve Sustainability Development Goal-03 “Good Health and Well Being”

Ayurveda is an ancient Indian Medical Science which was developed by the cumulative efforts of our ancient Rishis and is still practiced for over 3000 years. Ayurveda is Life Science. Ayurveda teaches a range of practices and natural remedies for leading a healthy lifestyle. Ayurveda is known for its therapeutic, promotive and curative concepts. Western medicine is the most conventional form of treatment across the globe today. However, the role of Ayurveda in health and well-being has started gaining worldwide acceptance after it was recognized by WHO as a Traditional medicine system by virtue of its essential elements of health, qualitative strength, and important clues for consistent functioning of life. Ayurveda medicines are time and again proved as medicines with least side effects. It is a holistic approach to cure the root cause and not just the symptoms. Ayurveda mainly focuses in preventing the diseases in a healthy person and treating the disease of an ill. Sustainable Development - Goal 3 aims to ensure healthy lives and promote well-being for all, at all ages. Health and well being are important at every stage of one’s life. Sustainable Developmental Goal-3 addresses all major health priorities:- Reproductive, Maternal, Newborn, Child and Adolescent health; communicable and non-communicable diseases; universal health coverage and access for all to safe, effective, quality and affordable medicines and vaccines. The Sustainable Development Goals makes a bold commitment to end the epidemics of AIDS, tuberculosis, malaria and other communicable diseases by 2030.

Safety Evaluation for Acute and Chronic Oral Toxicity of Maha Pigut Triphala Contains Three Medicinal Fruits in Sprague-Dawley Rats

Maha Pigut Triphala is the herbal mixture of three fruits consisting of T. bellirica, T. chebula, and E. officinalis also known as P. emblica. Humans regularly eat the fresh fruits of these plants on a daily basis. Maha Pigut Triphala is one of the widely known herbal medicinal formulas used in traditional Thai medicine. Besides studying pharmacological properties, attention should also be paid to the safety and toxicity studies of herbal medicines. The objective of the present study was to evaluate the acute and chronic oral toxicity of Maha Pigut Triphala (2:1:3) in Sprague-Dawley rats. A single dose of Maha Pigut Triphala at a concentration of 5000 mg/kg body weight was administered orally to female rats in the acute oral toxicity study. In the chronic oral toxicity study, male and female rats were treated with various concentrations of Maha Pigut Triphala (600, 1200, and 2400 mg/kg body weight) once daily for 270 consecutive days. The presence of abnormalities in the symptoms and behavior of the rats were observed and recorded throughout the experiment. Additionally, body weight, organ weight, and mortality were recorded. At the end of the study, blood samples were collected for hematological and blood chemistry analysis, while the internal organs were evaluated for gross pathological and histopathological changes. The acute oral toxicity study revealed no mortality and abnormal symptoms or behavior in Maha Pigut Triphala-treated rats. Moreover, gross pathological and histopathological findings did not reveal any abnormalities in the internal organs. In the chronic oral toxicity evaluation, although there were negligible changes in body weight, organ weight, and hematological and blood chemistry parameters in rats treated with Maha Pigut Triphala for 270 days, no behavioral or gross pathological and histopathological abnormalities were observed. Overall, the results of this study demonstrate that Maha Pigut Triphala (2:1:3) neither causes acute nor chronic oral toxicity in rats, proposing the safety of this herbal formula in animals prior to human trials and use.

Effect of coexisting nutrient divalent cations on cadmium transport in soil-herbal crop systems

Cadmium (Cd) pollution in Chinese herbal medicines poses a serious risk to medication safety. Regulating Cd uptake, transport, and accumulation in plants through ion-ion interactions offers a novel, environmentally sustainable, and practical approach to address this issue. However, the effects and underlying mechanisms of coexisting divalent cations zinc (Zn), magnesium (Mg), and manganese (Mn) on Cd uptake by Ligusticum sinense cv. Chuanxiong (L. chuanxiong) have not been comprehensively studied or well understood. In this study, the application of coexisting these cations (Zn, Mg, Mn) could significantly promote the growth of L. chuanxiong (21.11%–36.04%) and change the mobility of Cd in the soil-crop system. Specifically, adding Zn decreased Cd content in soil and plants by 18.23% and 20.62%, respectively, while Mg increased it by 10.99% and 62.27%. Mn addition, however, had no significant effect. Similar trends in soil enzyme activity were also observed with Zn, Mg, and Mn treatments. Simultaneously, the findings explore how coexisting divalent cations influence plant physiological responses, including photosynthesis and antioxidant capacities, enabling L. chuanxiong to better manage Cd stress. This study underscores the potential of ion-to-ion interactions as an effective approach to mitigate Cd accumulation, offering a practical and sustainable solution for enhancing the safety of Chinese herbal medicines. Additionally, the effects of mixed cation applications on Cd dynamics are complex, shaped by interactions between ion types, dosages, and their specific properties. These insights provide a foundation for developing more effective remediation strategies for Cd-contaminated soils, particularly in the cultivation of medicinal plants.

Comparative efficacy and safety of Chinese patent medicines for primary insomnia: a systematic review and network meta-analysis of 109 randomized trials

Comparative efficacy and safety of Chinese patent medicines for primary insomnia: a systematic review and network meta-analysis of 109 randomized trials

Network Meta-analysis of the clinical efficacy and safety of kidney-tonifying and bone-strengthening therapies for the treatment of rheumatoid arthritis with kidney deficiency type.

To compare the efficacy and safety of different Traditional Chinese Medicine (TCM)-based kidney-tonifying and bone-strengthening therapies for rheumatoid arthritis (RA). The current Bayesian network Meta-analysis compared different TCM-based kidney-tonifying and bone-strengthening therapies for RA. Eight electronic databases and two trial registration platforms were searched. RevMan 5.4 and Stata 16 software were employed. A total of 42 studies involving 3779 cases were included. The results showed that the most effective intervention for improving efficacy was Wanbi decoction; Bushen Quhan Zhiwang decoction was superior in reducing the incidence of adverse reactions; and Qiwei Tongbi oral liquid effectively reduced C-reactive protein and erythrocyte sedimentation rate levels. Combining TCMs with conventional Western Medicine can improve the clinical efficacy of RA treatments, reduce inflammatory indexes, and result in a higher safety profile. However, this conclusion needs to be verified by more high-quality randomized controlled trials.

Embracing innovation: A patient advocacy perspective on evolving trial designs

SMA Schweiz and SMA Europe, two patient advocacy organisations for the rare condition spinal muscular atrophy (SMA), work towards promoting the fastest possible access to safe and effective medicines for all individuals who can benefit from them. Their experience has shown that patient and public involvement at the design stage of clinical research directly impacts a product’s pathway to patients and leads to a better understanding of a product’s value later on. Furthermore, recent discussions about how complex clinical trial designs and decentralised clinical trials use innovative methods to conduct clinical research indicate their potential to make trials more flexible, personalised, and convenient for participants. In addition to helping shift current paradigms, innovative trial designs hold enormous potential to further advance medicines for the good of patient communities, especially in the area of rare diseases.

Hybrid Nanoparticle for Co-delivering Paclitaxel and Dihydroartemisinin to Exhibit Synergic Anticancer Therapeutics.

Anticancer treatment is required to provide effective and safe patient medicines. This research aided in developing and applying nanoparticles (NPs) for cancer treatment. The poor solubility of paclitaxel (PTX) restricts its therapeutic efficacy because of allergic side effects caused by formulation excipients. To overcome this, PTX was coupled with artemisinin derivatives and loaded into an NP drug delivery system to enhance its effects while addressing its low solubility. This study prepared and characterized a hybrid PLGA-lecithin NP containing dihydroartemisinin (DHA) and PTX for synergic anticancer therapy. A lyophilization study improved the stability of the NP drug formulations. Dual PTX- and DHA-loaded PLGA- and lecithin-based NPs were prepared using a single-step solvent evaporation method. The NP suspensions were lyophilized, and the types and ratios of cryoprotectants were investigated. The physicochemical properties of NPs and lyophilized cakes (Lyo-NPs) were characterized. The stability of the Lyo-NPs was investigated at 2-8°C and room conditions. The anticancer effects of the drug combination, NP suspension, and lyophilized powder were analyzed using an in vitro cytotoxicity assay and an in vivo model. The optimal PTX-DHA loaded PLGA-lecithin-NP was formulated (200 nm, PDI: 0.248 ± 0.003, Zeta potential: -33.60 ± 3.39 mV). Mannitol was selected for lyophilization. Lyo-NPs improved the stability of the NPs (1 year), wherein the physicochemical properties of the NPs were maintained (RDI was close to 1.0). An in-vitro cytotoxicity assay of PTX combined with DHA showed a synergistic anticancer effect (CI <1.0). The suppressive effects of Lyo-NPs on tumor growth in vivo were dose-dependent. While the cocktail of free drugs showed high toxicity (7.5 mg PTX-15 mg DHA/kg) in-vivo, Lyo-NPs showed no statistical differences in hematological and biochemical parameters compared to the control. Dual-drug-loaded hybrid PLGA-lecithin NP is a potential system to minimize severe side effects while enhancing antitumor efficacy, in which lyophilization is a key process to increase stability.

Theoretical Investigation of Physicochemical Properties, Bioactivity, and Toxicity of Common Anxiety Medications

AbstractPhysicochemical properties, bioactivity scores, toxicity, chemical reactivity descriptor (GCRD), polarizability, and UV–vis spectroscopy of 10 common medicines used for the treatment of anxiety have been investigated to understand their activity and adverse effect in the human body. GCRD, polarizability, and UV–vis data of the drug molecules have been analyzed at the density functional M06‐2X/cc‐pVTZ level. Molinspiration, Osiris Property Explorer, and the SwissTargetPrediction tools have been used to study the molecular and physicochemical properties, drug likeness/bioactivity scores, and toxicity of the drug molecules. The calculated results show that all drug molecules have good bioavailability and are orally active, which corroborate with the clinical data. Most of the theoretical results are first reported, and the predicted results agree well with the clinical data and published reports wherever available. The calculated GCRD parameters confirm that chlordiazepoxide (D3) is the most reactive drug molecule. Drug likeness and drug score indicate that alprazolam (D1), chlordiazepoxide (D3), paroxetine (D7), and selegiline (D9) are safe medicines for humans. The predicted toxicities also substantiate the clinical data. The BOILED‐Egg plot illustrates that as alprazolam (D1) and paroxetine (D7) are the substrates of the P‐glycoprotein (PGP+), they are actively pumped up from the brain or to the gastrointestinal lumen.

A systematic review and meta-analysis of the efficacy and safety of traditional Chinese medicine in the treatment of rhinosinusitis.

Rhinosinusitis (RS), a common inflammatory disorder, adversely affects quality of life and can progress to serious complications without intervention. Conventional therapies, including antibiotics and corticosteroids, exhibit inherent limitations and risks. Traditional Chinese medicine (TCM), with its extensive historical use in RS management, remains understudied in contemporary evaluations. This systematic review evaluates the efficacy and safety of TCM in RS treatment, aiming to guide clinical decision-making. A systematic search was undertaken in Chinese and English databases, such as CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, Web of Science, and other relevant databases, to gather randomized controlled trials of TCM for patients with RS from January 2014 to February 2024. Two researchers independently curated and synthesized data from eligible literature, conducted meta-analyses with ReviewManager 5.4.1, and assessed evidence quality via GRADEPro GDT. A total of 48 articles included 4490 patients, of which 2249 were control group and 2241 were in the experimental group. Meta-analytic outcomes revealed that the integration of TCM with western medicine conventional treatment significantly enhanced the total effective rate [risk ratio=1.20, 95% confidence interval (CI) (1.17, 1.23), P < 0.05] and yielded a notable reduction in Lund-Kennedy score [mean difference (MD)=-1.32, 95% CI (-1.72, -0.93), P < 0.05], Lund-Mackay score [MD=-1.13, 95% CI (-1.27, -1.00), P < 0.05], SNOT-20 score [MD=-3.02, 95% CI (-4.34, -1.69), P < 0.05], nasal congestion Visual Analogue Scale (VAS) score [MD=-1.05, 95% CI (-1.65, -0.45), P < 0.05], runny nose VAS score [MD=-0.84, 95% CI (-1.13, -0.54), P < 0.05], headache VAS score [MD=-0.90, 95% CI (-1.45, -0.35), P < 0.05], olfactory impairment VAS score [MD=-1.43, 95% CI (-1.75, -1.11), P < 0.05], and total TCM syndrome score [standardized mean difference (SMD)=-1.78, 95% CI (-2.58, -0.97), P < 0.05]. Additionally, significant decreases were observed in levels of tumor necrosis factor-α [SMD=-2.14, 95% CI (-3.42, -0.87), P < 0.05] and interleukin-6 [SMD=-1.64, 95% CI (-2.08, -1.21), P < 0.05], with statistical significance achieved for all measured outcomes. Regarding safety considerations, an insignificant variance was observed between the 2 therapeutic approaches, with no statistically discernible difference (P > 0.05). Combining TCM with western medicine in RS treatment yields superior outcomes over western medicine alone, with enhanced efficacy, reduced nasal symptoms, and lower inflammation. Rigorous multicenter RCTs are warranted to affirm these advantages and bolster the evidence for TCM in RS management.

Educational Case Study of the Total Plate Count of Jamu Gendong in Cirebon City

Indonesian herbal heritage that still survives and continues to be preserved. Jamu that is very well known by the people of Indonesia is jamu gendong. Based on the Regulation of the Head of the Food and Drug Administration of the Republic of Indonesia number 12 of 2014 concerning traditional medicines that are prohibited from circulating, namely traditional medicines that do not meet the quality safety and usefulness requirements, one of which meets the TPC test requirements. The Total Plate Count (TPC) test is used to calculate the number of bacteria that grow and develop in a sample, as well as a reference for determining the quality and safety of simplisia. One of the regulations of the Food and Drug Supervisory Agency (BPOM) no 32 of 2019 concerning the safety and quality requirements of traditional medicines that in the process of making liquid preparations of internal medicine must meet the requirements of a total plate number value of r &lt; 105 colonies / mL. The purpose of this study was to determine the TPC value before and after How to Make Good Fresh Herbal Medicine (CPJB) education and to determine the effect of CPJB education on jamu gendong rice kencur sellers in Kejaksan District and Kesambi District. Samples in this study were taken from 5 herbal medicine sellers. The results of this study showed the TPC value before CPJB education, sample 1 12 x 10-5, sample 2 1.4 x 10-4, sample 3 2.6 x 10-4, sample 4 3.6 x 10-4, sample 5 2.2 x 10-4. This study used leaflet media to conduct CPJB education. TPC value after CPJB education, in sample 1 amounted to 2.7 x 10-4. The conclusion of this study is that there is an effect of CPJB education on kencur rice herbal sellers, as evidenced by changes in TPC values before education and after education.

The Effect Red Betel Leaves (Piper Crocatum) On Pregnancy Gingivitis

Gingivitis is a periodontal disease that easily occurs in pregnant women, such as inflammation of the gums (3). The decrease in pH in the mouth, the influence of the hormones estrogen and progesterone during pregnancy causes gum inflammation (4), so safe therapy is needed such as boiled water from red betel leaves which can improve the oral hygiene status of gingivitis sufferers (11) and the inhibitory power of red betel leaf extract is very potently inhibits microorganisms that cause periodontal disease (12). The aim of this study was to determine whether there is an effect of boiled water from red betel leaves (piper crocatum) on pregnancy gingivitis. The method used in this research is quasi experimental with a pretest-posttest with control group design. The sample studied was 60 pregnant women, consisting of 30 pregnant women in the treatment group and 30 pregnant women in the control group. Data analysis used the Independent T-test. The results of the case group research in the pretest were 15 people (50%) of pregnant women with gingivitis and 13 people (43.6%) in the moderate category, 6 people (20%) in the post test results after intervention without gingivitis and 21 people (70%) in the mild category. ), while in the control group in the pretest, 19 people (63.3%) had mild category of pregnant women with gingivitis, 9 people (30%) in the moderate category, 17 people (56.7%) in the post test after intervention in the mild category, moderate category 11 people (36.7%), as well as the influence of boiled water from red betel leaves (piper crocatum) on pregnancy gingivitis (pvalue 0.000 &lt; 0.05). The conclusion is that boiled water from red betel leaves can reduce gingivitis so it can be used as a safe medicine to reduce gingivitis in pregnant women while maintaining oral and dental hygiene.

Efficacy and Safety of Zihua Wenfei Zhisou Granule in Treatment of Postinfectious Cough: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase II Clinical Trial.

To evaluate the efficacy and safety of Chinese medicine (CM) Zihua Wenfei Zhisou Granule (ZWZG) in postinfectious cough (PIC) patients with CM syndrome of wind-cold invading Fei (Lung, WCIF). This is a multicenter, randomized, double-blind, parallel-group, placebo-controlled phase II clinical trial. PIC patients with WCIF syndrome were recruited from the Respiratory Departments in 6 hospitals across China between March 2019 and December 2020. Eligible patients were randomly assigned to group A (ZWZG-matched placebo 15 g), group B (active ZWZG 15 g), and group C (active ZWZG 10 g plus ZWZG-matched placebo 5 g) in a 1:1:1 ratio. All medications were taken orally 3 times daily for 14 consecutive days. The primary outcomes were cough relief rate and cough disappearance rate. The secondary outcomes included time to cough relief, time to cough disappearance, and changes in cough symptom score (CSS), cough Visual Analog Scale (VAS) value, Cough-Specific Quality of Life Questionnaire (CQLQ) score, and CM syndrome score from baseline (day 0) to post-treatment (day 14). Adverse events (AEs) in each group were recorded. A total of 198 patients were included in the full analysis set (FAS) and safety analysis set (SS), while 183 were enrolled in the per-protocol analysis set (PPS). In the FAS population, the cough relief rate was 47.76%, 90.77% and 84.85% in groups A, B, and C, respectively; while the cough disappearance rate was 31.34%, 72.31% and 68.18%, respectively. The cough relief rates and cough disappearance rates in groups B and C were significantly higher than group A (P<0.0001). Both the median time to cough relief and cough disappearance in groups B and C were shorter than group A (P<0.0001). Compared with group A, groups B and C showed significantly greater improvements from baseline to post-treatment in CSS during daytime and nighttime as well as VAS (P<0.05). There were no significant differences in changes from baseline to post-treatment in CQLQ and CM syndrome scores among 3 groups (P>0.05). Results in the PPS population were consistent with those in the FAS population. Groups B and C showed lower incidence in AEs than group A (P<0.05), while there was no significant difference between groups B and C (P>0.05). No drug-related severe AEs were reported. ZWZG can increase cough disappearance rate and cough relief rate; and it is beneficial in shortening cough duration and reducing cough severity and frequency in patients suffering from PIC. It is safe and generally well tolerated. (Registration No. ChiCTR1900022078).

Change and Detection of Emotions Expressed on People’s Faces in Photos

Human emotions are an element of attention in various areas of interest such as psychology, marketing, medicine, and public safety. Correctly detecting human emotions is a complex matter. The more complex and visually similar emotions are, the more difficult they become to distinguish. Making visual modifications to the faces of people in photos in a way that changes the perceived emotion while preserving the characteristic features of the original face is one of the areas of research in deepfake technologies. The aim of this article is to showcase the outcomes of computer simulation experiments that utilize artificial intelligence algorithms to change the emotions on people’s faces. In order to detect and change emotions, deep neural networks discussed further in this article were used.

Phage-Derived Endolysins Against Resistant Staphylococcus spp.: A Review of Features, Antibacterial Activities, and Recent Applications.

Antimicrobial resistance is a significant global public health issue, and the dissemination of antibiotic resistance in Gram-positive bacterial pathogens has significantly increased morbidity, mortality rates, and healthcare costs. Among them, Staphylococcus, especially methicillin-resistant Staphylococcus aureus (MRSA), causes a wide range of diseases due to its diverse pathogenic factors and infection strategies. These bacteria also present significant issues in veterinary medicine and food safety. Effectively managing staphylococci-related problems necessitates a concerted effort to implement preventive measures, rapidly detect the pathogen, and develop new and safe antimicrobial therapies. In recent years, there has been growing interest in using endolysins to combat bacterial infections. These enzymes, which are also referred to as lysins, are a unique class of hydrolytic enzymes synthesized by double-stranded DNA bacteriophages. They possess glycosidase, lytic transglycosylase, amidase, and endopeptidase activities, effectively destroying the peptidoglycan layer and resulting in bacterial lysis. This unique property makes endolysins powerful antimicrobial agents, particularly against Gram-positive organisms with more accessible peptidoglycan layers. Therefore, considering the potential benefits of endolysins compared to conventional antibiotics, we have endeavored to gather and review the characteristics and uses of endolysins derived from staphylococcal bacteriophages, as well as their antibacterial effectiveness against Staphylococcus spp. based on conducted experiments and trials.

Drug-induced cholestasis (DIC) predictions based on in vitro inhibition of major bile acid clearance mechanisms.

Drug-induced cholestasis (DIC) is recognized as a major safety concern in drug development, as it represents one of the three types of drug-induced liver injury (DILI). Cholestasis is characterized by the disruption of bile flow, leading to intrahepatic accumulation of toxic bile acids. Bile acid regulation is a multifarious process, orchestrated by several hepatic mechanisms, namely sinusoidal uptake and efflux, canalicular secretion and intracellular metabolism. In the present study, we developed a prediction model of DIC using in vitro inhibition data for 47 marketed drugs on nine transporters and five enzymes known to regulate bile acid homeostasis. The resulting model was able to distinguish between drugs with or without DILI concern (p-value = 0.039) and demonstrated a satisfactory predictive performance, with the area under the precision-recall curve (PR AUC) measured at 0.91. Furthermore, we simplified the model considering only two processes, namely reversible inhibition of OATP1B1 and time-dependent inhibition of CYP3A4, which provided an enhanced performance (PR AUC = 0.95). Our study supports literature findings suggesting a contribution not only from a single process inhibition, but a rather synergistic effect of the key bile acid clearance processes in the development of cholestasis. The use of a quantitative model in the preclinical investigations of DIC is expected to reduce attrition rate in advanced development programs and guide the discovery and development of safe medicines.