Therapeutic efficacy of the drug Simparica® for demodicosis in dogs in the Kamianets-Podilskyi, Ukraine

The purpose of our research was to test the therapeutic efficacy of the acaricide «Simparica®» in combination with the biostimulator «Catosal» and the hepatoprotector «Tioprotectin» for demodicosis in dogs in the conditions of veterinary clinics in the Kamianets-Podilskyi, Ukraine. The study has been performed on dogs of different genders, ages and breeds that had a generalized form of demodicosis (affected at least 6 areas on the body of animals), to test the effectiveness of this drug in different treatment schemes. Acarological studies of scrapings from the skin of experimental animals for the presence of live or dead mites Demodex canis or their eggs have been carried out by the vital method according to D.O. Pryselkova. As a result of the conducted researches the choice of acaricidal drugs and development of complex therapeutic measures for demodicosis of dogs has been experimentally substantiated. The drug «Simparica®» has proved to be quite effective against demodicosis of dogs, even with a single use. The dependence of the effectiveness of the use of prolonged acaricide «Simparica®» on clinical forms of demodicosis has been shown. The absolute therapeutic effect of acaricide is obtained in the scaly form of demodicosis. However, in pustular and mixed clinical forms of demodicosis, its effectiveness decreased to 71.4 and 57.1%, respectively. In combination with the drug of pathogenetic therapy «Catosal» for pustular and mixed forms of demodicosis, the therapeutic efficacy of the drug «Simparica®» increases to 85.7%. When added to the scheme of hepatoprotector “Thioprotectin”, it is possible to achieve 100% therapeutic effect in pustular forms of demodicosis. However, in severe mixed form of demodicosis, the effectiveness was not absolute and was only 85.7%. In case of generalized demodicosis of dogs, regardless of clinical forms, it is recommended to use the acaricide «Simparica®» in combination with the drug «Catosal» and in the combination of «Catosal» and «Thioprotectin».

Distribution of Therapeutic Efficacy of Ranunculales Plants Used by Ethnic Minorities on the Phylogenetic Tree of Chinese Species

The medicinal properties of plants can be evolutionarily predicted by phylogeny-based methods, which, however, have not been used to explore the regularity of therapeutic effects of Chinese plants utilized by ethnic minorities. This study aims at exploring the distribution law of therapeutic efficacy of Ranunculales plants on the phylogenetic tree of Chinese species. We collected therapeutic efficacy data of 551 ethnomedicinal species belonging to five species-rich families of Ranunculales; these therapeutic data were divided into 15 categories according to the impacted tissues and organs. The phylogenetic tree of angiosperm species was used to analyze the phylogenetic signals of ethnomedicinal plants by calculating the net relatedness index (NRI) and nearest taxon index (NTI) in R language. The NRI results revealed a clustered structure for eight medicinal categories (poisoning/intoxication, circulatory, gastrointestinal, eyesight, oral, pediatric, skin, and urinary disorders) and overdispersion for the remaining seven (neurological, general, hepatobiliary, musculoskeletal, otolaryngologic, reproductive, and respiratory disorders), while the NTI metric identified the clustered structure for all. Statistically, NRI and NTI values were significant in 5 and 11 categories, respectively. It was found that Mahonia eurybracteata has therapeutic effects on all categories. iTOL was used to visualize the distribution of treatment efficacy on species phylogenetic trees. By figuring out the distribution of therapeutic effects of Ranunculales medicinal plants, the importance of phylogenetic methods in finding potential medicinal resources is highlighted; NRI, NTI, and similar indices can be calculated to help find taxonomic groups with medicinal efficacy based on the phylogenetic tree of flora in different geographic regions.

Chitosan Nanoparticle-Based System: A New Insight into the Promising Controlled Release System for Lung Cancer Treatment

Lung cancer has been recognized as one of the most often diagnosed and perhaps most lethal cancer diseases worldwide. Conventional chemotherapy for lung cancer-related diseases has bumped into various limitations and challenges, including non-targeted drug delivery, short drug retention period, low therapeutic efficacy, and multidrug resistance (MDR). Chitosan (CS), a natural polymer derived from deacetylation of chitin, and comprised of arbitrarily distributed β-(1-4)-linked d-glucosamine (deacetylated unit) and N-acetyl-d-glucosamine (acetylated unit) that exhibits magnificent characteristics, including being mucoadhesive, biodegradable, and biocompatible, has emerged as an essential element for the development of a nano-particulate delivery vehicle. Additionally, the flexibility of CS structure due to the free protonable amino groups in the CS backbone has made it easy for the modification and functionalization of CS to be developed into a nanoparticle system with high adaptability in lung cancer treatment. In this review, the current state of chitosan nanoparticle (CNP) systems, including the advantages, challenges, and opportunities, will be discussed, followed by drug release mechanisms and mathematical kinetic models. Subsequently, various modification routes of CNP for improved and enhanced therapeutic efficacy, as well as other restrictions of conventional drug administration for lung cancer treatment, are covered.

Design of Oral Sustained-Release Pellets by Modeling and Simulation Approach to Improve Compliance for Repurposing Sobrerol

Sobrerol, an oral mucolytic agent, in a recent study showed promise for treating multiple sclerosis. A human equivalent dose of 486 mg of sobrerol administered thrice daily (i.e., 1459 mg of daily dose) demonstrated the highest therapeutic efficacy for repurposing use, which also points out the poor compliance of administration. In this study, oral sustained-release pellets of sobrerol were successfully developed with evaluated manufacturing conditions and drug release kinetics. For design of the target drug product, we used a modeling and simulation approach to establish a predictive model of oral pharmacokinetic profile, by exploring the characteristics and correlations corresponding to the pharmacokinetics and pharmacodynamics of sobrerol, such as absorption lag time (0.18 h), time-scaling in vitro–in vivo correlation (tin-vitro = 0.494 tin-vivo − 0.0904), gastrointestinal transit time (8 h), minimum effective concentration (1.61 μg/mL), and duration of action (12.8 h). Results showed that the frequency of administration and the daily dose remarkably reduced by 33.3% (i.e., from thrice to twice daily) and 22.8%, respectively, which indicates that this prototype approach can be adopted for rapidly developing a modified-release dosage form of sobrerol, with improvement of compliance of administration and therapeutic efficacy.

The differential effects of tumor burdens on predicting the net benefits of ssCART-19 cell treatment on r/r B-ALL patients

The tumor burden (TB) is significantly related to the severity of cytokine release syndrome (CRS) caused by CAR-T cells, but its correlation with therapeutic efficacy has not been systematically studied. This study focused on the effects of the TB level on both the safety and efficacy of ssCART-19 as a treatment for r/r B-ALL. Taking the 5% tumor burden as the boundary, the study participants were divided into 2 groups, high and low tumor burden groups. Under this grouping strategy, the impacts of differential r/r B-ALL TBs on the clinical therapeutic efficacy (CR rate and long-term survival) and safety profiles after ssCART-19 cell treatment were analysed. 78 patients were reported in this study. The differential B-ALL TBs significantly affected the complete remission (CR) rates of patients treated with ssCART-19, with rates of 93.94% and 75.56% in the low and high TB groups, respectively (P = 0.0358). The effects of TBs on long-term therapeutic efficacy were further studied based on event-free survival (EFS) and overall survival (OS) profiles; both the OS and EFS of the low TB group were better than those of the high TB group, but the differences were not statistically significant. Importantly, the time points of TB measurement did not significantly affect the OS and EFS profiles regardless of whether the TBs were measured before or after fludarabine-cyclophosphamide (FC) preconditional chemotherapy. On the other hand, the severity of CRS was significantly correlated with the TB level (P = 0.0080), and the incidence of sCRS was significantly related to the TB level (the sCRS incidence increased as the TB level increased, P = 0.0224). Unexpectedly, the ssCART-19 cell expansion peaks were not significantly different (P = 0.2951) between the study groups. Patients with a low r/r B-ALL TB yield more net benefits from CAR-T treatment than those with a high TB in terms of safety and CR rate. These findings are critical and valuable for determining the optimal CAR-T cell treatment window for r/r B-ALL patients and will further the development of comprehensive and reasonable CAR-T cell treatment plans for r/r B-ALL patients with differential TBs.Trial registration: ClinicalTrials.gov identifier, NCT03919240.

Evaluation of the therapeutic efficacy of original and generic meloxicam in the treatment of acute neck pain

Introduction. In the structure of the global burden of diseases, back pain ranks first in the world in the list of causes of disability. Neck pain is one of the most common diseases of the musculoskeletal system. An integral part of the strategy for the treatment of acute neck pain is the use of original nonsteroidal anti-inflammatory drugs (NSAIDs) with high proven effectiveness.Objective. To conduct a comparative analysis of the therapeutic efficacy of the original drug meloxicam (Movalis) and its generic (Amelotex) in the treatment of patients with acute nonspecific musculoskeletal pain of cervical localization.Materials and methods. The article provides an assessment of the therapeutic effectiveness of the original drug meloxicam (Movalis) and its generic (Amelotex) in the treatment of patients with acute neck pain. Comparative analysis of the results of treatment of 108 patients hospitalized in the Branch of the MC JSC “Admiralteyskie Verfi” aged 18 to 60 years (58 men and 50 women) with a diagnosis of acute dorsalgia of cervical localization (M54.2 according to ICD-10). The average age of patients is 42.5 ± 11.1 years.Results. As a result of the clinical and neurological study and statistical processing of the data obtained, it was found that the use of Movalis in the treatment of patients with acute neck pain was more effective compared to the use of generic (Amelotex). In the Movalis group, the level of pain intensity and the index of disability after treatment was significantly lower than in the Amelotex group at an equivalent dose of 15 mg per day (p < 0.01). The analgesic effect in the group of patients receiving Movalis was longer. There was a significant decrease in sleep disorders associated with pain syndrome in the group (Movalis) compared with patients of the second group (Amelotex). Conclusions. The absence of therapeutic bioequivalence between Movalis and Amelotex revealed in our study determines the relevance of the choice of drugs for the complex therapy of patients of this profile. A multimodal approach to the strategy of treating neck pain, individually patient-oriented, including the use of effective and safe medicines, physical exercises, manual therapy, is optimal.>< 0.01). The analgesic effect in the group of patients receiving Movalis was longer. There was a significant decrease in sleep disorders associated with pain syndrome in the group (Movalis) compared with patients of the second group (Amelotex).Conclusions. The absence of therapeutic bioequivalence between Movalis and Amelotex revealed in our study determines the relevance of the choice of drugs for the complex therapy of patients of this profile. A multimodal approach to the strategy of treating neck pain, individually patient-oriented, including the use of effective and safe medicines, physical exercises, manual therapy, is optimal.