experimental drug
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Author(s):  
Felix R De Bie ◽  
Catherine M Avitabile ◽  
Luc Joyeux ◽  
Holly L Hedrick ◽  
Francesca M Russo ◽  
...  

Congenital diaphragmatic hernia (CDH) is a complex malformation characterised by a triad of pulmonary hypoplasia, pulmonary hypertension (PH) and cardiac ventricular dysfunction. Much of the mortality and morbidity in CDH is largely accounted for by PH, especially when persistent beyond the neonatal period and refractory to available treatment. Gentle ventilation, haemodynamic optimisation and pulmonary vasodilation constitute the foundations of neonatal treatment of CDH-related PH (CDH-PH). Moreover, early prenatal diagnosis, the ability to assess severity and the developmental nature of the condition generate the perfect rationale for fetal therapy. Shortcomings of currently available clinical therapies in combination with increased understanding of CDH pathophysiology have spurred experimental drug trials, exploring new therapeutic mechanisms to tackle CDH-PH. We herein discuss clinically available neonatal and fetal therapies specifically targeting CDH-PH and review the most promising experimental treatments and future research avenues.


2021 ◽  
Vol 12 (4) ◽  
Author(s):  
B. V. Borysevych ◽  
◽  
V. V. Lisova ◽  
I. M. Derkach ◽  
S. S. Derkach ◽  
...  

Iron (IV) clathrochelate based on a macrobicyclic ligand of the hexahydrazide type is a unique compound that contains iron in a rare high valence IV. Preclinical and clinical studies of this complex, which were started for the first time in Ukraine, have an important theoretical and practical consequence as this complex can be recommended as an active substance in iron-containing drugs with antianemic action. In conducting preclinical studies of new drugs, pathomorphological studies are important because they are a necessary step in studying the biological response of animals to the action of test substances. It was found that some pathological changes develop in the body of white mice under conditions of experimental acute and chronic iron (IV) clathrochelate intoxication. They correlated with the dose of the test compound. During chronic intoxication, the microscopic changes in the liver and kidney of white mice treated with iron (IV) clathrochelate at a dose of 1/10 DL50 were similar to the microscopic changes in the liver and kidney of mice treated with the experimental drug at a dose of 1/5 DL50. However, the severity of these changes was lower, reflecting a lower degree of organ damage. In the myocardium of mice treated with iron (IV) clathrochelate at a dose of 1/5 DL50 on the 10th day, as in acute iron (IV) clathrochelate poisoning, only edema was recorded. The prospects for further research are the study of microscopic changes in the organs of laboratory animals of other species during experimental iron (IV) clathrochelate toxicosis.


2021 ◽  
Author(s):  
Xinrui Wang ◽  
Tina C. Wan ◽  
Katherine R. Kulik ◽  
Amelia Lauth ◽  
John W. Lough ◽  
...  

It is estimated that up to one billion cardiomyocytes (CMs) can be lost during myocardial infarction (MI), which results in contractile dysfunction, adverse ventricular remodeling, and systolic heart failure. Pharmacologic strategies that target factors having both pro-apoptotic and anti-proliferative functions in CMs may be useful for the treatment of ischemic heart disease. One such multifunctional candidate for drug targeting is the acetyltransferase Tip60, which is a member of the MYST family of acetyltransferases known to acetylate both histone and non-histone protein targets that have been shown in cultured cancer cells to promote apoptosis and to initiate the DNA damage response (DDR) thereby limiting cellular expansion. Using a murine model, we recently published findings demonstrating that CM-specific disruption of the Kat5 gene encoding Tip60 markedly protected against the damaging effects of MI. In the experiments described here, in lieu of genetic targeting, we administered TH1834, an experimental drug designed to specifically inhibit the acetyltransferase domain of Tip60. We report that, similar to the effect of disrupting the Kat5 gene, daily systemic administration of TH1834 beginning 3 days after induction of MI and continuing for two weeks of a 4-week timeline resulted in improved systolic function assessed by echocardiography, reduced apoptosis and scarring, reduced expression of markers of the DDR, and increased activation of the CM cell-cycle. Our results support that idea that drugs that inhibit the acetyltransferase activity of Tip60 may be useful agents for the treatment of ischemic heart disease.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sheida Nasr Esfahani ◽  
Mohammad Sadegh Damavandi ◽  
Parisa Sadeghi ◽  
Zahrasadat Nazifi ◽  
Azhar Salari-Jazi ◽  
...  

AbstractWith the progressive and ever-increasing antibacterial resistance pathway, the need for novel antibiotic design becomes critical. Sulfonamides are one of the more effective antibiotics against bacteria. In this work, several novel sulfonamide hybrids including coumarin and isoxazole group were synthesized in five steps starting from coumarin-3-carboxylic acid and 3-amino-5-methyl isoxazole and assayed for antibacterial activity. The samples were obtained in good to high yield and characterized by FT-IR, 13C-NMR, 1H-NMR, CHN and melting point techniques. 3D-QSAR is a fast, easy, cost-effective, and high throughput screening method to predict the effect of the compound's efficacy, which notably decreases the needed price for experimental drug assay. The 3D-QSAR model displayed acceptable predictive and descriptive capability to find r2 and q2 the pMIC of the designed compound. Key descriptors, which robustly depend on antibacterial activity, perhaps were explained by this method. According to this model, among the synthesized sulfonamide hybrids, 9b and 9f had the highest effect on the gram-negative and gram-positive bacteria based on the pMIC. The 3D-QSAR results were confirmed in the experimental assays, demonstrating that our model is useful for developing new antibacterial agents. The work proposes a computationally-driven strategy for designing and discovering new sulfonamide scaffold for bacterial inhibition.


2021 ◽  
Vol 2021 ◽  
pp. 1-26
Author(s):  
Maqsood Ahmad ◽  
Muhammad Saeed ◽  
Muhammad Javaid ◽  
Ebenezer Bonyah

Polymers, drugs, and almost all chemical or biochemical compounds are frequently modeled as diverse ω -cyclic, acyclic, bipartite, and polygonal shapes and regular graphs. Molecular descriptors (topological indices) are the numerical quantities and computed from the molecular graph Γ (2D lattice). These descriptors are highly significant in quantitative structure-property or activity relationship (QSPR and QSAR) modeling that provides the theoretical and the optimal basis to expensive experimental drug design. In this paper, we study three isomeric natural polymers of glucose (polysaccharides), namely, cellulose, glycogen, and amylopectin (starch), having promising pharmaceutical applications, exceptional properties, and fascinating molecular structures. We intend to investigate and compute various closed-form formulas such as ABC , GA , sum-connectivity χ − 1 / 2 , ABC 4 , GA 5 , and Sanskruti indices for the aforementioned macromolecules. Also, we present the closed-form formulas for the first, second, modified, and augmented Zagreb indices, inverse and general Randić indices, and symmetric division deg, harmonic, and inverse sum indices. Furthermore, we provide a comparative analysis using 3D graphs for these families of macromolecules to clarify their nature.


2021 ◽  
Vol 4 (2) ◽  
pp. 52-57
Author(s):  
O. L. Tishyn ◽  
I. D. Yuskiv ◽  
L. L. Yuskiv ◽  
Zn. M. Perih ◽  
O. M. Bogach

The article presents data on the effectiveness of new domestic antiparasitic drug “Insectostop for dogs and cats” in comparison to the reference drugs “Burdi Fipro for dogs” and “Burdi Fipro for cats” that is used for therapeutic and prophylactic purposes against ectoparasitosis of dogs and cats of different breeds. According to the results of the research, the parasitism of fleas of Ctenocephalus canis, C. felis and Pulex irritans species and parasitiform mites of the Ixodes ricinus and Dermacentor reticulatus species and sarcoptiform mites of the species Otodectes cynotis were detected on experimental animals. Clinically, this was inspected by redness, inflammation of the skin, itching reflex, the emergence of papules on the skin, scales. Based on the results, it was found that 8 hours after usage of the experimental drug “Insectostop for dogs and cats” its effectiveness in syphonapterosis of dogs was 87.9 %, and after usage of the reference drug “Bourdie Fipro for dogs” – 86.9 %, and in experiments on cats, the effectiveness of the experimental drug for siphonapterosis in cats was 92.4 %, and the reference drug “Bourdie Fipro for cats” – 90.3 %. Starting from the first and third days after usage of drugs on the fur of dogs and cats of the experimental and control groups, parasitological studies did not reveal fleas of the species Ctenocephalus canis, C. felis and Pulex irritans. So starting from the first day, the experimental and reference drugs showed 100 % effectiveness during the siphonapterosis in dogs and cats. During the ixodidosis of dogs, it was found that at the 8-th hour after usage of the experimental drug “Insectostop for dogs and cats” its effectiveness was 82.9 %, and after usage of the reference drug “Bourdie Fipro for dogs” – 81.3 %. At the 24-th hour after usage of the experimental drug, its effectiveness was 97.6 %, and after usage of the reference drug – 95.9 %. At the 72nd hour of the experiment, no adult representatives of the species Ixodes ricinus and Dermacentor reticulatus were found on the fur of dogs of these groups. Thus, at 72 hours after usage of the experimental and reference drug, they showed 100 % efficiency on adult Ixodes mites. During the Otodectesis of dogs it was found that on the 7th day, effectiveness of the experimental drug was 75.6 %, on the 14th day – 98.1 % and after usage of the reference drug “Bourdi Fipro for dogs” its effectiveness on the 7th day was 73.5 %, and on the 14th – 98.3 %. At 21-st days after treatment of animals with drugs as a result of clinical examination and parasitological examination of dogs mites of the species Otodectes cynotis were not detected. In experiments on cats, on the 7th day after usage of experimental drug, its effectiveness during Otodectesis of cats was 76.9 %, and after usage of reference drug – 77.1 %. As a result of clinical examination and parasitological study of the experimental and control groups of animals on the 14th day after treatment of the auricles of cats with mites of the species Otodectes cynotis was not detected. Thus, usage of both drugs promotes the release of Otodectesis in dogs from parasites on the 21st day of the experiment, and cats – on the 14th day. Tests have shown that the experimental drug “Insectostop for dogs and cats” (100 ml of the drug contains the active substance: fipronil – 10 g) does not cause skin irritation, dermatitis, seborrhea, allergic and other side effects, that the drug is well tolerated by dogs and cats and doesn’t give any side effects and changes of clinical condition of animals.


2021 ◽  
Vol Volume 13 ◽  
pp. 755-779
Author(s):  
Violette Deleeuw ◽  
Adelbert De Clercq ◽  
Julie De Backer ◽  
Patrick Sips

2021 ◽  
Vol 40 (2) ◽  
pp. 77-82
Author(s):  
Konstantin N. Listov ◽  
Roman A. Yakovlev

Increasing the level of antioxidants in the human body plays an important role in increasing longevity. Studies on small laboratory animals showed that in the main group with an increased content of antioxidant enzymes, life expectancy was 20% higher than in the comparison group with age and heart diseases. Thus, the hypothesis is confirmed that a high content of active free radical molecules causes aging and the data obtained on small laboratory animals will increase the human lifespan. This fact is associated with the occurrence of heart and oncological diseases, as well as other age-related pathologies. In order to prevent the development of the above diseases, a drug was developed with an innovative composition of complex-compatible components. The experimental drug contains substances with an increased content of antioxidants for the prevention of cerebrovascular accidents, such as dihydroquercetin and black grape extract. And also vitamins and amino acids: succinic acid, ascorbic acid, glycine. The choice of the composition of the experimental drug was carried out on the basis of the antioxidant properties of these groups of substances, which are widely known, and their combined use will become a potentiated synergy of the selected components and complement their effect. Due to the fact that the classical technology for the production of effervescent dosage forms does not allow combining the components of the composition of the experimental drug, the task of developing an individual technology for combining the acid and alkaline fractions of the formulation by separating the components at the stage of the technological process of drying the raw material was solved. Thanks to this, it became possible to separate the granulation of acid and alkaline components, which made it possible to stabilize the tabletting mixture (3 tables, bibliography: 8 refs.).


Author(s):  
Elliot S. Gerlach ◽  
Sophie Altamirano ◽  
J. Marina Yoder ◽  
Tony S. Luggya ◽  
Andrew Akampurira ◽  
...  

Half maximal inhibitory concentrations (IC50) to the experimental drug ATI-2307 and complete inhibition (IC90) of the common clinically used antifungal drug amphotericin B were determined by microbroth dilution assay for a collection of 69 clinical isolates of Cryptococcus neoformans from Uganda that had high fluconazole IC50 values. The majority of the clinical isolates tested had fluconazole IC50 at or above 8 µg/mL, but were susceptible to both amphotericin B (IC90 ≤1 μg/mL) and ATI-2307 (IC50 ≤0.0312 µg/mL). No correlation between increased fluconazole minimum inhibitory concentration (MIC) and ATI-2307 or amphotericin B MIC was observed, suggesting that the cellular changes impacting fluconazole susceptibility did not impact the effectiveness of ATI-2307. Our results suggest that ATI-2307 is a promising new antifungal drug for use in the context of high fluconazole or other antifungal drug MICs and/or in combination drug therapy regimens.


2021 ◽  
Vol 12 ◽  
Author(s):  
Mengli Xiao ◽  
Jiake Ying ◽  
Yang Zhao ◽  
Qingna Li ◽  
Yingpan Zhao ◽  
...  

Background: The successful application of randomized, double-blind placebo-controlled studies requires maximum blinding. Organoleptic properties of the placebo should be similar to the drug, making it difficult to distinguish between the two. The uniqueness of traditional Chinese medicine (TCM) preparations makes it challenging to prepare placebo. Evaluation of the TCM placebo simulation effect can determine whether the preparation of placebo can be genuinely blind in clinical trials. There is still a lack of well-established methods to evaluate TCM placebos. Hence, this study aimed to explore the evaluation methodology of TCM placebo simulation.Methods: An independent evaluation method and three comparative evaluation methods were proposed, and three dosage forms (oral liquid, capsule, and granule) were tested. The independent evaluation, in which each person was given an experimental drug or a placebo, gave an overall assessment of organoleptic properties in a blind state. We comparatively evaluated the similarity in organoleptic properties between the experimental drug and placebo. According to different distribution methods, we divided comparative evaluation methods into three. In method 1, the evaluator was given the experimental drug and placebo and was told that there must be a placebo among them. In method 2, each evaluator was randomly assigned to the combination group or two investigational drugs group. In method 3, the evaluator was assigned to a set of three coded samples, numbered by random three-digit numbers, each different, two of which were identical, and the two samples were equally frequent.Results: In the independent evaluation, there was no difference between TCM placebo and experimental drugs in a blind state at the level of p = 0.05. Even though the comparative evaluation methods enabled identification of potential differences between the two samples, methods 2 and 3 were better than method 1 in eliminating psychological factors. Also, in method 3, the completely random method combined with the blind method eliminated the subjectivity and objectivity bias and improved the experiment’s credibility compared with the previous two methods.Conclusion: Regardless of the methods that could evaluate the placebo’s simulated effect in actual clinical trials, we suggest that independent evaluation and comparative evaluation (method 3) should be combined to reflect better whether the placebo is truly blind.


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