scholarly journals Synthetic Amphoteric Cryogels as an Antidote against Acute Heavy Metal Poisoning

Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7601
Author(s):  
Alzhan Z. Baimenov ◽  
Ildar R. Fakhradiyev ◽  
Dmitriy A. Berillo ◽  
Timur Saliev ◽  
Sergey V. Mikhalovsky ◽  
...  
Keyword(s):  
Heavy Metals ◽  
Morphological Structure ◽  
Chelating Agent ◽  
Acute Poisoning ◽  
Control Group ◽  
High Survival ◽  
Agent Based ◽  
In Vivo Experiments ◽  
Acid Sodium Salt

The effectiveness of an amphoteric cryogel (AAC) as an oral sorbent (enerosorbent) for the treatment of acute poisoning of small animals (rats) with heavy metals (HMs) was studied in in vivo experiments. The morphological structure of the cryogel was examined using scanning electron microscopy/energy-dispersive X-ray analysis and confocal microscopy. The use of the cryogel in the treatment of rats administered an LD50 dose of Cd(NO3)2, CsNO3, Sr(NO3)2, or HgCl2 in aqueous solution showed their high survival rate compared to the control group, which did not receive such treatment. The histological and chemical analysis of internal tissues and the biochemical analysis of the blood of the experimental animals showed the effectiveness of the cryogel in protecting the animals against the damaging effect of HMs on the organism comparable with unithiol, a chelating agent based on 2,3-dimercapto-1-propane sulfonic acid sodium salt (DMPS) approved for the treatment of acute poisoning with some heavy metals.

Agitation Techniques to Enhance Drainage of Retained Hemothorax

2020 ◽  
pp. 155335062097800
Author(s):  
Ian A. Makey ◽  
Nitin A. Das ◽  
Samuel Jacob ◽  
Magdy M. El-Sayed Ahmed ◽  
Colleen M. Makey ◽  
...  
Keyword(s):  
Trauma Surgery ◽  
Control Group ◽  
In Vivo Experiments ◽  
Vibration Technique ◽  
Retained Hemothorax ◽  
And Control ◽  
Negative Conclusion ◽  
Benchtop Model

Background. Retained hemothorax (RH) is a common problem in cardiothoracic and trauma surgery. We aimed to determine the optimum agitation technique to enhance thrombus dissolution and drainage and to apply the technique to a porcine-retained hemothorax. Methods. Three agitation techniques were tested: flush irrigation, ultrasound, and vibration. We used the techniques in a benchtop model with tissue plasminogen activator (tPA) and pig hemothorax with tPA. We used the most promising technique vibration in a pig hemothorax without tPA. Statistics. We used 2-sample t tests for each comparison and Cohen d tests to calculate effect size (ES). Results. In the benchtop model, mean drainages in the agitation group and control group and the ES were flush irrigation, 42%, 28%, and 2.91 ( P = .10); ultrasound, 35%, 27%, and .76 ( P = .30); and vibration, 28%, 19%, and 1.14 ( P = .04). In the pig hemothorax with tPA, mean drainages and the ES of each agitation technique compared with control (58%) were flush irrigation, 80% and 1.14 ( P = .37); ultrasound, 80% and 2.11 ( P = .17); and vibration, 95% and 3.98 ( P = .06). In the pig hemothorax model without tPA, mean drainages of the vibration technique and control group were 50% and 43% (ES = .29; P = .65). Discussion. In vitro studies suggested flush irrigation had the greatest effect, whereas only vibration was significantly different vs the respective controls. In vivo with tPA, vibration showed promising but not statistically significant results. Results of in vivo experiments without tPA were negative. Conclusion. Agitation techniques, in combination with tPA, may enhance drainage of hemothorax.

In vivo protection studies of bis-quaternary 2-(hydroxyimino)-N-(pyridin-3-yl) acetamide derivatives (HNK oximes) against tabun and soman poisoning in Swiss albino mice

2017 ◽  
Vol 36 (12) ◽  
pp. 1270-1285 ◽  
Author(s):  
P Kumar ◽  
D Swami ◽  
DP Nagar ◽  
KP Singh ◽  
J Acharya ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Ache Activity ◽  
Lethal Dose ◽  
Acute Poisoning ◽  
Control Group ◽  
Swiss Albino Mice ◽  
Albino Mice ◽  
Brain Ache Activity ◽  
Protection Index

The study reports antidotal efficacy of three HNK [ bis quaternary 2-(hydroxyimino)-N-(pyridin-3yl) acetamide derivatives] and pralidoxime (2-PAM), against soman and tabun poisoning in Swiss albino mice. Protection index (PI) was determined (treatment doses: HNK oximes, ×0.20 of their median lethal dose (LD50) and 2-PAM, 30 mg/kg, intramuscularly (im)) together with atropine (10 mg/kg, intraperitoneally). Probit log doses with difference of 0.301 log of LD50 of the nerve agents administered and inhibition of acetylcholinesterase (AChE) activity by 50% (IC50) was calculated at optimized time in brain and serum. Using various doses of tabun and soman (subcutaneously (sc)), in multiples of their IC50, AChE reactivation ability of the oximes was studied. Besides, acute toxicity (0.8× LD50, im, 24 h postexposure) of HNK-102 and 2-PAM was also compared by determining biochemical, hematological variables and making histopathological observations. Protection offered by HNK-102 against tabun poisoning was found to be four times higher compared to 2-PAM. However, nearly equal protection was noted with all the four oximes against soman poisoning. HNK-102 reactivated brain AChE activity by 1.5 times more than 2-PAM at IC50 dose of soman and tabun. Acute toxicity studies of HNK-102 and 2-PAM showed sporadic changes in urea, uric acid, aspartate aminotransferase, and so on compared to control group, however, not supported by histopathological investigations. The present investigation showed superiority of newly synthesized HNK-102 oxime over standard 2-PAM, as a better antidote, against acute poisoning of tabun (4.00 times) and soman (1.04 times), in Swiss albino mice.

Photodynamic effects of Radachlorin® on cervical cancer model

2005 ◽  
Vol 09 (12) ◽  
pp. 835-840 ◽  
Author(s):  
Sun-Young Kwak ◽  
Dae-Seog Lim ◽  
Su-Mi Bae ◽  
Yong-Wook Kim ◽  
Joon-Mo Lee ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Golgi Apparatus ◽  
Biological Significance ◽  
Annexin V ◽  
Light Irradiation ◽  
Control Group ◽  
Cancer Model ◽  
In Vivo Experiments

Photodynamic therapy (PDT) has been reported to be effective for treating various tumors and induce apoptosis in many tumor cells. In this study, we examined a biological significance of PDT with a chlorin-based photosensitizer, Radachlorin®, in a cervical cancer model, TC-1 cells. When TC-1 cells were exposed to varied doses of Radachlorin® with light irradiation (6.25 J/cm2), PDT induced a dose-dependent growth inhibition of TC-1 cells. All of these cells were significantly damaged after light irradiation and categorized to be early and late apoptosis, as determined by annexin V staining. Radachlorin® localized primarily into the Golgi apparatus of cells in 12 h of the treatment, and weak fluorescence intensity was also detected in mitochondria. On the other hand, in the in vivo experiments, following light irradiation (100 J/cm2), retarded tumor growth was significant in mice treated with Radachlorin®, as compared to the control group. Taken together, we propose that PDT after the application of Radachlorin® may induce the Golgi apparatus-mediated apoptosis of cervical cancer cells in vitro, and also be effective in the mice system.

scholarly journals Isolation Purification and Partial Characterization of Antisnake Venom Plant Peptide (BRS-P19) from Bauhinia rufescens (LAM FAM) Seed as Potential Alternative to Serum-Based Antivenin

2020 ◽  
pp. 18-26
Author(s):  
I. Sani ◽  
A.A. Umar ◽  
S.A. Jiga ◽  
F. Bello ◽  
A. Abdulhamid ◽  
...  
Keyword(s):  
Antioxidant Enzymes ◽  
Research Work ◽  
Gel Filtration ◽  
Inhibitory Effect ◽  
Untreated Group ◽  
Control Group ◽  
In Vivo Experiments ◽  
Potential Alternative

Several studies have been reported on active peptides isolated from some medicinal plants, which were effective inhibitors against snake venom induced toxicities. Hence, the aim of this research work was to isolate, purify and characterize an antisnake venom plant peptide from Bauhinia rufescens seed that can serve as potential alternative to serum-based antivenins. B. rufescens seed was collected, duly identified, authenticated and processed. The peptide was isolated from the seed and purified using gel filtration chromatography and SDS-PAGE and then named as BRS-P19. Venom Phospholipase A2 (VPLA2) was used for the study and was isolated from Naja nigricollis venom. Albino mice of both sexes were used for in vivo experiments. They were divided into seven (7) groups of three (3) mice each. Group 1 served as normal control, group 2 were injected with VPLA2 only, group 3 and 4 were injected with VPLA2 then treated with BRS-P19 at doses of 0.2 and 0.4 mg/kg b.w. respectively, while mice in group 5 were injected with VPLA2 then treated with standard antivenin, group 6 and 7 were injected with VPLA2 followed by administration of ascorbic acid and α-tocopherol respectively. In all the groups, hepatic and renal levels of reactive oxygen species (ROS), lipid peroxidation (MDA) and activities of antioxidant enzymes were determined. The results showed that, the BRS-P19 has molecular weight of ~19kD. Its percentage in vitro inhibitory effect against VPLA2 was 91.85 ± 0.32%. For the in vivo study, the animals treated with 0.4 mg/kg b.w. of the BRS-P19 showed a significant (P<0.05) decrease in the hepatic and renal ROS and MDA levels when compared with the VPLA2 untreated group. But, the activities of the antioxidant enzymes in all the treated groups were significantly (P<0.05) increased by the BRS-P19 at 0.4 mg/kg b.w. when compared to the VPLA2 untreated group. Based on these findings, it has been established that, BRS-P19 has antisnake venom effect through inhibition of VPLA2 and antioxidant activity as the possible mechanisms of action.

scholarly journals Antifungal Activity of an Original Amino-Isocyanonaphthalene (ICAN) Compound Family: Promising Broad Spectrum Antifungals

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 903
Author(s):  
Miklós Nagy ◽  
Gábor Szemán-Nagy ◽  
Alexandra Kiss ◽  
Zsolt László Nagy ◽  
László Tálas ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Candida Species ◽  
Fungal Pathogens ◽  
Clinical Strain ◽  
Control Group ◽  
Multiple Drug ◽  
Species Structure ◽  
In Vivo Experiments

Multiple drug resistant fungi pose a serious threat to human health, therefore the development of completely new antimycotics is of paramount importance. The in vitro antifungal activity of the original, 1-amino-5-isocyanonaphthalenes (ICANs) was evaluated against reference strains of clinically important Candida species. Structure-activity studies revealed that the naphthalene core and the isocyano- together with the amino moieties are all necessary to exert antifungal activity. 1,1-N-dimethylamino-5-isocyanonaphthalene (DIMICAN), the most promising candidate, was tested further in vitro against clinical isolates of Candida species, yielding a minimum inhibitory concentration (MIC) of 0.04–1.25 µg/mL. DIMICAN was found to be effective against intrinsically fluconazole resistant Candida krusei isolates, too. In vivo experiments were performed in a severly neutropenic murine model inoculated with a clinical strain of Candida albicans. Daily administration of 5 mg/kg DIMICAN intraperitoneally resulted in 80% survival even at day 13, whereas 100% of the control group died within six days. Based on these results, ICANs may become an effective clinical lead compound family against fungal pathogens.

Promising in vitro Anti-Toxoplasma gondii effects of commercial Chitosan

2020 ◽  
Vol 20 ◽  
Author(s):  
Bahman Rahimi Esboei ◽  
Masoud Keighobadi ◽  
Hajar Ziaei Hezarjaribi ◽  
Mahdi Fakhar ◽  
Ahmad Daryani ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Control Group ◽  
Low Molecular Weight ◽  
In Vitro Activity ◽  
Obligate Intracellular ◽  
In Vivo Experiments ◽  
Ic50 Values ◽  
Acute Toxoplasmosis

Background: Toxoplasmosis is a disease that results from infection with an obligate intracellular T. gondii parasite, one of the world's most common parasites. Considering the complications of chemical drugs and the need for an appropriate drug combination for treatment of toxoplasmosis and also considering the antimicrobial potential of chitosan, as a natural source, this study was aimed to evaluate in vitro activity of commercial chitosan (CC) on T. gondii. Methods: In this experimental study, the tachyzoites of T. gondii was collected from the peritoneal exudates from infected Balb/c mice. The tachyzoites were diluted in phosphate buffer saline (PBS). Chitosan with low molecular weight was commercially purchased. Then, at concentrations of 10, 50, 100 and 200 µg/mL and after 30, 60, 120 and 180 minutes the viability of tachyzoites were determined by using trypan blue 0.1%. Anti-T.gondii activity of CC in all concentration was significantly higher than pyrimethamine as control group (P=0.05). Results: The concentration of 200 µg/mL of CC had the highest effects and killed 30.5, 52, 59 and 81.5% of tachyzoites after 30, 60, 120 and 180 minutes. Moreover, IC50 values of CC were 515, 171, 12.5 and <10 μg/mL in comparison with pyrimethamine as 58.82 μg/mL for 30, 60, 120, and 180 min of exposure time. Conclusion: Our results indicate chitosan in low molecular weight had potent activity against T. gondii tachyzoites and could be an appropriate candidate for treatment of at least acute toxoplasmosis, certainly, after complementary in vivo experiments.

scholarly journals PER2-mediated ameloblast differentiation via PPARγ/AKT1/β-catenin axis

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Wushuang Huang ◽  
Xueqing Zheng ◽  
Mei Yang ◽  
Ruiqi Li ◽  
Yaling Song
Keyword(s):  
Circadian Rhythm ◽  
Circadian Disruption ◽  
Cell Junctions ◽  
Control Group ◽  
Enamel Matrix ◽  
Enamel Formation ◽  
In Vivo Experiments ◽  
Pparγ Agonist

AbstractCircadian rhythm is involved in the development and diseases of many tissues. However, as an essential environmental regulating factor, its effect on amelogenesis has not been fully elucidated. The present study aims to investigate the correlation between circadian rhythm and ameloblast differentiation and to explore the mechanism by which circadian genes regulate ameloblast differentiation. Circadian disruption models were constructed in mice for in vivo experiments. An ameloblast-lineage cell (ALC) line was used for in vitro studies. As essential molecules of the circadian system, Bmal1 and Per2 exhibited circadian expression in ALCs. Circadian disruption mice showed reduced amelogenin (AMELX) expression and enamel matrix secretion and downregulated expression of BMAL1, PER2, PPARγ, phosphorylated AKT1 and β-catenin, cytokeratin-14 and F-actin in ameloblasts. According to previous findings and our study, BMAL1 positively regulated PER2. Therefore, the present study focused on PER2-mediated ameloblast differentiation and enamel formation. Per2 knockdown decreased the expression of AMELX, PPARγ, phosphorylated AKT1 and β-catenin, promoted nuclear β-catenin accumulation, inhibited mineralization and altered the subcellular localization of E-cadherin in ALCs. Overexpression of PPARγ partially reversed the above results in Per2-knockdown ALCs. Furthermore, in in vivo experiments, the length of incisor eruption was significantly decreased in the circadian disturbance group compared to that in the control group, which was rescued by using a PPARγ agonist in circadian disturbance mice. In conclusion, through regulation of the PPARγ/AKT1/β-catenin signalling axis, PER2 played roles in amelogenin expression, cell junctions and arrangement, enamel matrix secretion and mineralization during ameloblast differentiation, which exert effects on enamel formation.

scholarly journals Control of Strongyles in First-Season Grazing Ewe Lambs by Integrating Deworming and Thrice-Weekly Administration of Parasiticidal Fungal Spores

Pathogens ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1338
Author(s):  
Mathilde Voinot ◽  
Rodrigo Bonilla ◽  
Sérgio Sousa ◽  
Jaime Sanchís ◽  
Miguel Canhão-Dias ◽  
...  
Keyword(s):  
Fungal Spores ◽  
Test Group ◽  
Mucor Circinelloides ◽  
Gastrointestinal Parasites ◽  
Control Group ◽  
First Year ◽  
Cell Parameters ◽  
In Vivo Experiments ◽  
Ewe Lambs

Parasiticidal fungi have been used in several in vivo experiments in livestock farms worldwide, constituting an effective tool for the biocontrol of gastrointestinal parasites in grazing animals. In the first year of study, two groups of eight first-season pasturing ewe lambs infected by strongyles were dewormed with albendazole, and then, the test group received an oral dose of 106 chlamydospores of Mucor circinelloides and 106 Duddingtonia flagrans individually and thrice a week from mid-September to May (FS1), while the control group remained without fungi (CT1). In the second year, two new groups of first-season grazing ewe lambs were treated with ivermectin and subjected to the same experimental design (FS2 and CT2, respectively). The anthelmintic efficacy was 96.6% (CT1), 95.6% (FS1), 96.1% (CT2), and 95.1% (FS2). The counts of strongyle egg output increased in the control groups (CT1 and CT2) throughout the study and reached numbers higher than 600 eggs per gram of feces (EPG), while in FS1 and FS2, they were <250 EPG. The values of red blood cell parameters registered for CT1 and CT2 were lower than those of the reference standards, while a significant increment was recorded in FS1 and FS2, and values within the physiological range were attained. It is concluded that integrating efficient anthelminthic deworming with rotational pasturing and the regular intake of chlamydospores of M. circinelloides and D. flagrans provides a helpful strategy for maintaining low levels of strongyle egg output in first-season grazing ewe lambs and improves their health status.

scholarly journals Attenuation of Knee Osteoarthritis Progression in Mice through Polarization of M2 Macrophages by Intra-Articular Transplantation of Non-Cultured Human Adipose-Derived Regenerative Cells

2021 ◽  
Vol 10 (19) ◽  
pp. 4309
Author(s):  
Kohei Kamada ◽  
Takehiko Matsushita ◽  
Takahiro Yamashita ◽  
Tomoyuki Matsumoto ◽  
Hideki Iwaguro ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Type Ii Collagen ◽  
Control Group ◽  
Knee Oa ◽  
In Vivo Experiments ◽  
Osteoarthritis Progression ◽  
Regenerative Cells ◽  
Related Proteins

Adipose-derived regenerative cells (ADRCs) are non-cultured heterogeneous or mixed populations of cells obtained from adipose tissue by collagenase digestion. The injection of ADRCs have been tried clinically for the treatment of osteoarthritis (OA). The purpose of this study was to evaluate the effect of intra-articular transplantation of human ADRCs on OA progression in mice and the effect of ADRCs on macrophage polarization. In in vivo experiments, BALB/c-nu mice with knee OA received intra-articular transplantation of either phosphate buffered-saline or human ADRCs. OA progression was evaluated histologically and significantly attenuated in the ADRC group at both four and eight weeks postoperatively. The expression of OA-related proteins in the cartilage and macrophage-associated markers in the synovium were examined by immunohistochemistry. The numbers of MMP-13-, ADAMTS-5-, IL-1β-, IL-6- and iNOS-positive cells significantly decreased, and type II collagen- and CD206-positive cells were more frequently detected in the ADRC group compared with that in the control group. In vitro co-culture experiments showed that ADRCs induced macrophage polarization toward M2. The results of this study suggest that the intra-articular transplantation of human ADRCs could attenuate OA progression possibly by reducing catabolic factors in chondrocytes and modulating macrophage polarization.

scholarly journals Experimental and clinical evaluation of mefloquine effectiveness against the infection caused by SARS-CoV-2

2021 ◽  
Author(s):  
KN Filin ◽  
VD Gladkikh ◽  
VN Bykov
Keyword(s):  
Clinical Trial ◽  
Virus Titer ◽  
Control Group ◽  
Efficacy And Safety ◽  
Syrian Hamsters ◽  
Mild Disease ◽  
In Vivo Experiments ◽  
Changes Over Time ◽  
Symptom Changes

The efficacy of mefloquine has not been studied in the in vivo experiments and clinical trials involving COVID-19 patients. The study was aimed to assess the effects of mefloquine on the SARS-CoV-2 accumulation in the lungs of infected animals and to study the efficacy and safety of mefloquine compared to hydroxychloroquine in patients with COVID-19. During the experiment, a total of 96 Syrian hamsters were infected with SARS-CoV-2. Accumulation of the virus in lungs was compared in the groups of animals treated with mefloquine and ribavirin and in the control group. During the clinical trial, the mefloquine and hydroxychloroquine safety and efficacy in patients with mild and moderate COVID-19 (172 individuals) was assessed based on the symptom changes over time and the computed tomography results. The experiment showed that the SARS-CoV-2 accumulation in the lungs of Syrian hamsters 6 days after infection and mefloquine treatment was 2.2 ± 0.18 lg PFU/g, which was lower (p < 0.05) than in the control group (3.5 ± 0.21 lg PFU/g) and ribavirin group (5.2 ± 0.05 lg PFU/g). During the clinical trial, it was found that 50.0% of patients in the mefloquine group and 32.4% in the hydroxychloroquine group (р < 0.05) developed a mild disease, and the completely resolved respiratory failure was registered in 76.5% and 44.6%, respectively (р < 0.001). Adverse events were observed in 86.7 % and 77% of patients in the mefloquine and hydroxychloroquine groups, respectively (р > 0.05). Thus, during the experiment, mefloquine contributed to the faster virus titer reduction in the lungs. During the clinical trial, the mefloquine efficacy was non-inferiority or, based on a number of indicators, higher compared to hydroxychloroquine, with comparable safety.

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