scholarly journals Pharmacological activity and targeted delivery of supramolecular fenbendazole obtained by mechanochemical technology with various components

2021 ◽  
Vol 15 (2) ◽  
pp. 64-71
Author(s):  
A. I. Varlamova ◽  
I. A. Arkhipov ◽  
V. E. Abramov ◽  
M. V. Arisov ◽  
S. S. Khalikov ◽  
...  
Keyword(s):  
Small Intestine ◽  
Targeted Delivery ◽  
High Performance ◽  
Trichinella Spiralis ◽  
Disodium Salt ◽  
Control Group ◽  
Trace Quantity ◽  
Intestinal Nematode ◽  
Licorice Extract ◽  
Sodium Dioctyl

The purpose of the research is studying the influence of various components on the targeted delivery of fenbendazole and evaluation of their efficacy in mice experimentally infected with Trichinella spiralis.Materials and methods. The experiment used 80 white mice experimentally infected with T. spiralis, at a dose of 200 larvae per animal. Each group of 10 animals was administered intragastrically solid dispersion of fenbendazole (SDF) with polyvinyl pyrrolidone (PVP), arabinogalactan (AG), disodium salt of glycyrrhizinic acid (Na2 GA), sodium dioctyl sulfosuccinate (SDS), licorice extract (LE) and hydroxyethyl starch (HES) at a single dose of 2.0 mg/kg of active substance as compared with the fenbendazole substance at the same dose. The control group did not receive the drug. The anthelmintic efficacy was studied by the results of necropsy of the small intestine of mice on the second day after drugs administration. The concentration of fenbendazole and its metabolites in the small intestine was determined by high-performance liquid chromatography with tandem mass spectrometry detection.Results and discussion. SDF with PVP, AG, Na2 GA, SDS, LE and HES showed 98.0, 94.9, 96.6, 100, 86.0 and 81.0% efficacy against intestinal nematode T. spiralis at a dose of 2.0 mg/kg of AS (fenbendazole). The maximum concentration of fenbendazole and its metabolites – sulfone and sulfoxide - was determined in the small intestine wall of animals on the second day after SDF with SDS administration and amounted to 3117.8, 614.6 and 2998.6 ng/g respectively. After fenbendazole substance administration, the drug and its metabolites were found in trace quantity. 

scholarly journals Biological Activity of Fenbendazole Solid Dispersion Obtained by Mechanochemical Technology with Various Components for Targeted Delivery

2020 ◽  
Vol 14 (1) ◽  
pp. 75-80
Author(s):  
Anastasia I. Varlamova
Keyword(s):  
Solid Dispersion ◽  
Active Ingredient ◽  
Targeted Delivery ◽  
Trichinella Spiralis ◽  
Anthelmintic Activity ◽  
Gastrointestinal Nematodes ◽  
Control Group ◽  
Acid Sodium Salt ◽  
Licorice Extract ◽  
Flotation Technique

The purpose of the research is studying anthelmintic efficacy of fenbendazole solid dispersion obtained by mechanochemical technology with various components for targeted delivery. Materials and methods. The tests were conducted on 80 white mice infected experimentally with Trichinella spiralis and 145 sheep infected spontaneously with gastrointestinal nematodes. In case of each helminthosis, animals in different groups of 8–10 units each were given, orally, as a single dose, a fenbendazole solid dispersion (FSD) with polyvinylpyrrolidone (PVP), arabinogalactan (AG), glycyrrhizinic acid sodium salt (NaGA), dioctylsulphosuccinate sodium (NaDSS), licorice extract (LE) and hydroxyethylstarch (HES) in a dose of 2.0 mg/kg of the active ingredient as compared to fenbendazole drug at 2.0 mg/kg. A group of animals that were not given the drug was a control group. Anthelmintic activity of the preparations was considered based on dissection of the mouse small bowel and data from the sheep coproovoscopic examination carried out by the flotation technique before and 15 days after application of such drugs. Results and discussion. FSD with PVP, AG, NaGA, NaDSS, LE and HES in a dose of 2.0 mg/kg of the active ingredient (fenbendazole) showed 100; 98.7; 99.8; 100; 96.8 and 95.3% activity in mice against T. spiralis respectively; in sheep – 100; 96.3; 98.0; 100; 94.6 and 93.8% effectiveness against Nematodirus spp., and 100; 97.5; 98.6; 100; 97.0 and 96.5% activity against other species of the gastrointestinal Strongylata at 22.6–27.2% effectiveness of the main drug, namely, the active ingredient fenbendazole.

The protease phenotype and crystalline nature of the granules of intraepithelial mast cells in Trichinella spiralis-infected mice

1995 ◽  
Vol 53 ◽  
pp. 818-819
Author(s):  
D.S. Friend ◽  
N. Ghildyal ◽  
M.F. Gurish ◽  
K.F. Austen ◽  
R.L. Stevens
Keyword(s):  
Small Intestine ◽  
Mast Cells ◽  
Epithelial Cells ◽  
Lamina Propria ◽  
Trichinella Spiralis ◽  
Intestinal Epithelial ◽  
Carboxypeptidase A ◽  
C3h Mice ◽  
Granule Morphology ◽  
Crystalline Nature

Trichinella spiralis induces a profound mastocytosis and eosinophilia in the small intestine of the infected mouse. Mouse mast cells (MC) store in their granules various combinations of at least five chymotryptic chymases [designated mouse MC protease (mMCP) 1 to 5], two tryptic proteases designated mMCP-6 and mMCP-7 and an exopeptidase, carboxypeptidase A (mMC-CPA). Using antipeptide, protease -specific antibodies to these MC granule proteases, immunohistochemistry was done to determine the distribution, number and protease phenotype of the MCs in the small intestine and spleen 10 to >60 days after Trichinella infection of BALB/c and C3H mice. TEM was performed to evaluate the granule morphology of the MCs between intestinal epithelial cells and in the lamina propria (mucosal MCs) and in the submucosa, muscle and serosa of the intestine (submucosal MCs).As noted in the table below, the number of submucosal MCs remained constant throughout the study. In contrast, on day 14, the number of MCs in the mucosa increased ~25 fold. Increased numbers of MCs were observed between epithelial cells in the mucosal crypts, in the lamina propria and to a lesser extent, between epithelial cells of the intestinal villi.

Development and Characterization Colchicine-Loaded PEGylated Gelatin Nanoparticles for Targeted Delivery to Tumor

2013 ◽  
Vol 6 (2) ◽  
pp. 2058-2063
Author(s):  
G D Chandrethiya ◽  
P K Shelat ◽  
M N Zaveri
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
High Performance ◽  
Entrapment Efficiency ◽  
Stability Study ◽  
Spherical Particles ◽  
Precipitation Method ◽  
Antitumoral Activity ◽  
Gelatin Nanoparticles

PEGylated gelatin nanoparticles loaded with colchicine were prepared by ethanol precipitation method. Poly-(ethylene glycol)-5000-monomethylether (MPEG 5000), a hydrophilic polymer, was used to pegylate gelatin.  Gluteraldehyde was used as cross-linking agent. To obtain a high quality product, major formulation parameters were optimized.  Spherical particles with mean particles of 193 nm were measured by a Malvern particle size analyzer. Entrapment efficiency was found to be 71.7 ± 1.4% and determined with reverse phase high performance liquid charomatography (RP-HPLC). The in vitro drug release study was performed by dialysis bag method for a period of 168 hours. Lyophilizaton study showed sucrose at lower concentrations proved the best cryoprotectant for this formulation.  Stability study revealed that lyophilized nanoparticles were equally effective (p < 0.05) after one year of storage at 2-8°C with ambient humidity. In vitro antitumoral activity was accessed using the MCF-7 cell line by MTT assay.  The IC50 value was found to be 0.034 μg/ml for the prepared formulation. The results indicate that PEGylated gelatin nanoparticles could be utilized as a potential drug delivery for targeted drug delivery of tumors.  

scholarly journals Biodistribution of the radiophamarceutical sodium pertechnetate (Na99mTcO4) after massive small bowel resection in rats

2007 ◽  
Vol 22 (6) ◽  
pp. 430-435 ◽  
Author(s):  
Dâmaso de Araújo Chacon ◽  
Irami Araújo-Filho ◽  
Arthur Villarim-Neto ◽  
Amália Cínthia Meneses Rêgo ◽  
Ítalo Medeiros Azevedo ◽  
...  
Keyword(s):  
Small Intestine ◽  
Short Bowel Syndrome ◽  
Intestinal Mucosa ◽  
Intestinal Resection ◽  
Small Bowel Resection ◽  
Control Group ◽  
Short Bowel ◽  
Massive Resection ◽  
Mucosal Thickness ◽  
Misleading Interpretation

PURPOSE: To evaluate the biodistribution of sodium pertecnetate (Na99mTcO4) in organs and tissues, the morphometry of remnant intestinal mucosa and ponderal evolution in rats subjected to massive resection of the small intestine. METHODS: Twenty-one Wistar rats were randomly divided into three groups of 7 animals each. The short bowel (SB) group was subjected to massive resection of the small intestine; the control group (C) rats were not operated on, and soft intestinal handling was performed in sham rats. The animals were weighed weekly. On the 30th postoperative day, 0.l mL of Na99mTcO4, with mean activity of 0.66 MBq was injected intravenously into the orbital plexus. After 30 minutes, the rats were killed with an overdose of anesthetic, and fragments of the liver, spleen, pancreas, stomach, duodenum, small intestine, thyroid, lung, heart, kidney, bladder, muscle, femur and brain were harvested. The biopsies were washed with 0.9% NaCl.,The radioactivity was counted using Gama Counter WizardTM 1470, PerkinElmer. The percentage of radioactivity per gram of tissue (%ATI/g) was calculated. Biopsies of the remaining jejunum were analysed by HE staining to obtain mucosal thickness. Analysis of variance (ANOVA) and the Tukey test for multiple comparisons were used, considering p<0.05 as significant. RESULTS: There were no significant differences in %ATI/g of the Na99mTcO4 in the organs of the groups studied (p>0.05). An increase in the weight of the SB rats was observed after the second postoperative week. The jejunal mucosal thickness of the SB rats was significantly greater than that of C and sham rats (p<0.05). CONCLUSION: In rats with experimentally-produced short bowel syndrome, an adaptive response by the intestinal mucosa reduced weight loss. The biodistribution of Na99mTcO4 was not affected by massive intestinal resection, suggesting that short bowel syndrome is not the cause of misleading interpretation, if an examination using this radiopharmaceutical is indicated.

scholarly journals Metabolic Evaluation of Urine from Patients Diagnosed with High Grade (HG) Bladder Cancer by SPME-LC-MS Method

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2194
Author(s):  
Kamil Łuczykowski ◽  
Natalia Warmuzińska ◽  
Sylwia Operacz ◽  
Iga Stryjak ◽  
Joanna Bogusiewicz ◽  
...  
Keyword(s):  
Thin Film ◽  
Bladder Cancer ◽  
High Performance ◽  
Biomarker Discovery ◽  
Solid Phase ◽  
Biological Fluids ◽  
Reversed Phase ◽  
Control Group ◽  
Metabolic Evaluation ◽  
Metabolomic Profiling

Bladder cancer (BC) is a common malignancy of the urinary system and a leading cause of death worldwide. In this work, untargeted metabolomic profiling of biological fluids is presented as a non-invasive tool for bladder cancer biomarker discovery as a first step towards developing superior methods for detection, treatment, and prevention well as to further our current understanding of this disease. In this study, urine samples from 24 healthy volunteers and 24 BC patients were subjected to metabolomic profiling using high throughput solid-phase microextraction (SPME) in thin-film format and reversed-phase high-performance liquid chromatography coupled with a Q Exactive Focus Orbitrap mass spectrometer. The chemometric analysis enabled the selection of metabolites contributing to the observed separation of BC patients from the control group. Relevant differences were demonstrated for phenylalanine metabolism compounds, i.e., benzoic acid, hippuric acid, and 4-hydroxycinnamic acid. Furthermore, compounds involved in the metabolism of histidine, beta-alanine, and glycerophospholipids were also identified. Thin-film SPME can be efficiently used as an alternative approach to other traditional urine sample preparation methods, demonstrating the SPME technique as a simple and efficient tool for urinary metabolomics research. Moreover, this study’s results may support a better understanding of bladder cancer development and progression mechanisms.

scholarly journals RADT-23. IMPACT OF REIRRADIATION UTILIZING STEREOTACTIC RADIOSURGERY ON RECURRENT GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii186-ii186
Author(s):  
O’Dell Patrick ◽  
H Nickols ◽  
R LaRocca ◽  
K Sinicrope ◽  
D Sun ◽  
...  
Keyword(s):  
Stereotactic Radiosurgery ◽  
Median Survival ◽  
High Performance ◽  
Performance Status ◽  
Treatment Options ◽  
Methylation Status ◽  
Initial Therapy ◽  
Recurrent Glioblastoma ◽  
Control Group ◽  
The Impact

Abstract BACKGROUND Patients who have recurrent glioblastoma have limited treatment options. We conducted a retrospective review of patients with recurrent glioblastoma treated with standard initial radiation and temozolomide with tumor treating fields to investigate whether reirradiation using radiosurgery would be associated with improved outcomes. METHODS We reviewed the records of 54 consecutively treated patients with recurrent glioblastoma with ECOG 0 or 1 at recurrence and conducted Kaplan-Meier analysis with Log-rank testing to determine significance between groups. RESULTS We identified 24 patients who were treated without radiation therapy (control) while 30 patients underwent re-irradiation using radiosurgery (ReSRS) with a median total dose of 25Gy in five fractions. All patients had completed standard initial therapy, and there was no difference in the time to recurrence between the two groups (10 months for control, 15 months for ReSRS, [P = 0.17, HR for progression 0.65 (95% CI 0.38-1.13)]. A larger proportion of patients in the control arm (54%) had subtotal or gross total resection of the recurrence compared with the ReSRS group (44%, P &lt; 0.05). The majority of patients had recurrence confirmed with biopsy (18/22 in control group, 25/31 in the ReSRS group). MGMT methylation status did not differ between control vs ReSRS (29% vs. 27%). ReSRS was associated with improved median survival from the time of first recurrence of 11.6 months versus 3.8 months in the control arm [P&lt; 0.0001, HR for death 0.33 (95% CI 0.18-0.6)]. CONCLUSIONS In a group of patients with high performance status diagnosed with recurrent glioblastoma, reirradiation with stereotactic radiosurgery was associated with nearly one year median survival after recurrence. Additional analyses are warranted to determine the impact of concurrent systemic therapies with irradiation and underlying tumor or patient factors to predict outcomes.

scholarly journals Lactobacillus plantarum ATG-K2 and ATG-K6 Ameliorates High-Fat with High-Fructose Induced Intestinal Inflammation

2021 ◽  
Vol 22 (9) ◽  
pp. 4444
Author(s):  
Miey Park ◽  
Eun-Jung Park ◽  
So-Hyeun Kim ◽  
Hae-Jeung Lee
Keyword(s):  
Small Intestine ◽  
Cell Injury ◽  
Intestinal Inflammation ◽  
Liver Weight ◽  
Diet Group ◽  
Normal Diet ◽  
Control Group ◽  
High Fat ◽  
Inflammatory Reactions ◽  
High Fructose

Obesity has become a worldwide health problem, and many significant inflammatory markers have been associated with the risk of side effects of obesity and obesity-related diseases. After a normal diet or high-fat diet with high-fructose water (HFHF) for 8 weeks, male Wistar rats were divided randomly into four experimental groups according to body weight. Next, for 8 weeks, a normal diet, HFHF diet, and HFHF diet with L. plantarum strains ATG-K2 or ATG-K6 were administered orally. Compared to the control group, the HFHF diet group showed significantly increased visceral fat, epididymal fat, and liver weight. The mRNA and protein expression levels of FAS and SREBP-1c were higher in the HFHF diet group than in the HFHF diet with L. plantarum strains ATG-K2 and ATG-K6. The HFHF diet with L. plantarum strain ATG-K2 showed significantly decreased inflammatory cytokine expression in the serum and small intestine compared to the HFHF diet group. Furthermore, histological morphology showed minor cell injury, less severe infiltration, and longer villi height in the small intestine ileum of the HFHF diet with L. plantarum strains groups than in the HFHF diet group. These results suggest that L. plantarum strains K2 and K6 may help reduce intestinal inflammation and could be used as treatment alternatives for intestinal inflammatory reactions and obesity.

scholarly journals The Effect of Administration of a Phytobiotic Containing Cinnamon Oil and Citric Acid on the Metabolism, Immunity, and Growth Performance of Broiler Chickens

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 399
Author(s):  
Magdalena Krauze ◽  
Monika Cendrowska-Pinkosz ◽  
Paulius Matuseviĉius ◽  
Anna Stępniowska ◽  
Paweł Jurczak ◽  
...  
Keyword(s):  
Drinking Water ◽  
Small Intestine ◽  
Citric Acid ◽  
Beneficial Effect ◽  
Growth Performance ◽  
Broiler Chickens ◽  
Coliform Bacteria ◽  
Control Group ◽  
Cinnamon Oil ◽  
Nonesterified Fatty Acids

It was postulated that a phytobiotic preparation containing cinnamon oil and citric acid added to drinking water for chickens in a suitable amount and for a suitable time would beneficially modify the microbiota composition and morphology of the small intestine, thereby improving immunity and growth performance without inducing metabolic disorders. The aim of the study was to establish the dosage and time of administration of such a phytobiotic that would have the most beneficial effect on the intestinal histology and microbiota, production results, and immune and metabolic status of broiler chickens. The experiment was carried out on 980 one-day-old male chickens until the age of 42 days. The chickens were assigned to seven experimental groups of 140 birds each (seven replications of 20 individuals each). The control group (G-C) did not receive the phytobiotic. Groups CT-0.05, CT-0.1, and CT-0.25 received the phytobiotic in their drinking water in the amount of 0.05, 0.1, and 0.2 mL/L, respectively, at days 1–42 of life (continuous application, CT). The birds in groups PT-0.05, PT-0.5, and PT-0.25 received the phytobiotic in the same amounts, but only at days 1–7, 15–21, and 29–35 of life (periodic application, PT). Selected antioxidant and biochemical parameters were determined in the blood of the chickens, as well as parameters of immune status and redox status. The morphology of the intestinal epithelium, composition of the microbiome, and production parameters of chickens receiving the phytobiotic in their drinking water were determined as well. The addition of a phytobiotic containing cinnamon oil and citric acid to the drinking water of broiler chickens at a suitable dosage and for a suitable time can beneficially modify the microbiome composition and morphometry of the small intestine (total number of fungi p < 0.001, total number of aerobic bacteria p < 0.001; and total number of coliform bacteria p < 0.001 was decreased) improving the immunity and growth performance of the chickens (there occurred a villi lengthening p = 0.002 and crypts deepening p = 0.003). Among the three tested dosages (0.05, 0.1, and 0.25 mL/L of water) of the preparation containing cinnamon oil, the dosage of 0.25 mL/L of water administered for 42 days proved to be most beneficial. Chickens receiving the phytobiotic in the amount of 0.25 mL/L had better growth performance, which was linked to the beneficial effect of the preparation on the microbiome of the small intestine, metabolism (the HDL level p = 0.017 was increased; and a decreased level of total cholesterol (TC) p = 0.018 and nonesterified fatty acids (NEFA) p = 0.007, LDL p = 0.041, as well as triacylglycerols (TAG) p = 0.014), and immune (the level of lysozyme p = 0.041 was increased, as well as the percentage of phagocytic cells p = 0.034, phagocytosis index p = 0.038, and Ig-A level p = 0.031) and antioxidant system (the level of LOOH p < 0.001, MDA p = 0.002, and the activity of Catalase (CAT) p < 0.001 were decreased, but the level of ferric reducing ability of plasma (FRAP) p = 0.029, glutathione p = 0.045 and vitamin C p = 0.021 were increased).

scholarly journals Murine hepatoma treatment with mature dendritic cells stimulated by Trichinella spiralis excretory/secretory products

Parasite ◽  
2020 ◽  
Vol 27 ◽  
pp. 47
Author(s):  
Jing Ding ◽  
Xiaolei Liu ◽  
Bin Tang ◽  
Xue Bai ◽  
Yang Wang ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Tumor Growth ◽  
Antitumor Effect ◽  
Trichinella Spiralis ◽  
Critical Role ◽  
Tumor Model ◽  
Control Group ◽  
Tumor Inhibition ◽  
Significant Difference ◽  
Secretory Products

Excretory/Secretory Products (ESPs) of the nematode Trichinella spiralis contain antitumor-active substances that inhibit tumor growth. Mature dendritic cells (DCs) play a critical role in the antitumor immunity of the organism. As pathogen-derived products, it ought to be discussed whether T. spiralis ESPs will reduce the antitumor effect of mature DCs from the host before it is applied to patients’ tumors. Therefore, the aim of this work was to evaluate the immunological effect of DCs stimulated by T. spiralis ESPs in H22 tumor-bearing mice. H22 tumor model mice in this study were randomly divided into four groups according to the treatment: PBS control group, ESP group, DCs group, and DCs stimulated with T. spiralis ESP (ESP+DCs group). The antitumor effect was evaluated by tumor inhibition rate and cytokine detection using ELISA. The results showed significant inhibition in tumor growth in the ESP+DCs, DCs and ESP groups when compared with the PBS control group (p < 0.01, p < 0.01, and p < 0.05, respectively). However, no significant difference was observed on tumor inhibition rates between the ESP+DCs and DCs groups. The decrease in IL-4, IL-6, and IL-10, and the increase in IFN-γ between the DCs and ESP+DCs groups were also not significant. Therefore, DCs stimulated by ESP did not reduce the antitumor effect of mature DCs, which demonstrated that the T. spiralis ESP would not affect the antitumor effect of mature DCs by modulating the immune response of the host, and that ESPs are safe in antitumor immunology when applied in a tumor model mice.

Sign in / Sign up

Export Citation Format

Share Document