scholarly journals Immobilized Bisphosphonates as Potential Inhibitors of Bioprosthetic Calcification: Effects on Various Xenogeneic Cardiovascular Tissues

Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 65
Author(s):  
Irina Y. Zhuravleva ◽  
Anna A. Dokuchaeva ◽  
Elena V. Karpova ◽  
Tatyana P. Timchenko ◽  
Anatoly T. Titov ◽  
...  

Calcification is the major factor limiting the clinical use of bioprostheses. It may be prevented by the immobilization of bisphosphonic compounds (BPs) on the biomaterial. In this study, we assessed the accumulation and structure of calcium phosphate deposits in collagen-rich bovine pericardium (Pe) and elastin-rich porcine aortic wall (Ao) and bovine jugular vein wall (Ve) cross-linked with glutaraldehyde (GA) or diepoxy compound (DE). These tissues were then modified with pamidronic (PAM) acid or 2-(2′-carboxyethylamino)ethylidene-1,1-bisphosphonic (CEABA) acid. Tissue transformations were studied using Fourier-transform infrared spectroscopy. After subcutaneous implantation of the biomaterials in 220 rats, calcification dynamics were examined using atomic absorption spectrophotometry, light microscopy after von Kossa staining, and scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy The calcium content in all GA-cross-linked tissues and DE-cross-linked Ao increased to 100–160 mg/g on day 60 after implantation. BPs prevented the accumulation of phosphates on the surface of all materials and most effectively inhibited calcification in GA-cross-linked Ao and DE-cross-linked Pe. PAM containing -OH in the R1 group was more effective than CEABA containing -H in R1. The calcification-inhibitory effect of BPs may be realized through their ability to block nucleation and prevent the growth of hydroxyapatite crystals.

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4720
Author(s):  
Arlindo César Matias Pereira ◽  
Helison de Oliveira Carvalho ◽  
Danna Emanuelle Santos Gonçalves ◽  
Karyny Roberta Tavares Picanço ◽  
Abrahão Victor Tavares de Lima Teixeira dos dos Santos ◽  
...  

This study aimed to evaluate and compare the effects of co-treatment with purified annatto oil (PAO) or its granules (GRA, Chronic®) with that of testosterone on the orchiectomy-induced osteoporosis in Wistar rats. After surgery, rats were treated from day 7 until day 45 with testosterone only (TES, 7 mg/kg, IM) or TES + PAO or GRA (200 mg/kg, p.o.). The following parameters were evaluated: food/water intake, weight, HDL, LDL, glucose, triglycerides (TG), total cholesterol (TC), alkaline phosphatase levels, blood phosphorus and calcium contents, femur weight, structure (through scanning electron microscopy), and calcium content (through atomic absorption spectrophotometry). Our results show that orchiectomy could significantly change the blood lipid profile and decrease bone integrity parameters. Testosterone reposition alone could improve some endpoints, including LDL, TC, bone weight, and bone calcium concentration. However, other parameters were not significantly improved. Co-treatment with PAO or GRA improved the blood lipid profile and bone integrity more significantly and improved some endpoints not affected by testosterone reposition alone (such as TG levels and trabeculae sizes). The results suggest that co-treatment with annatto products improved the blood lipid profile and the anti-osteoporosis effects of testosterone. Overall, GRA had better results than PAO.


1969 ◽  
Vol 52 (4) ◽  
pp. 708-714 ◽  
Author(s):  
William L Hoover ◽  
John C Reagor ◽  
Julianne C Garner

Abstract Samples of plant or animal tissue are digested in a mixture of HNO3, H2SO4, and HClO4. Lead released in the digestion is entrained with strontium sulfate. The sulfate precipitate is separated from the digest and then converted to the carbonate by agitation with ammonium carbonate solution. The carbonate precipitate is dissolved in 1N HNO3, and lead is determined by atomic absorption spectrophotometry. Good recovery of lead (100 ± 3%) was observed except in samples with high calcium content (> 1%). For the latter samples, good recoveries were obtained after separation of the calcium from the digested samples. Moderate quantities of the following elements do not interfere: Al, Fe, P, Sn, Ca, Bi, and Tl. Most elements are soluble as sulfates and, hence, do not interfere. The procedure is rugged. Dry samples containing from 0.5 ppm to 1% lead can be routinely analyzed.


2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Darine Villela ◽  
Victoria Fairbanks Atherino ◽  
Larissa de Sá Lima ◽  
Anderson Augusto Moutinho ◽  
Fernanda Gaspar do Amaral ◽  
...  

The glutamatergic modulation of melatonin synthesis is well known, along with the importance of astrocytes in mediating glutamatergic signaling in the central nervous system. Pinealocytes and astrocytes are the main cell types in the pineal gland. The objective of this work was to investigate the interactions between astrocytes and pinealocytes as a part of the glutamate inhibitory effect on melatonin synthesis. Rat pinealocytes isolated or in coculture with astrocytes were incubated with glutamate in the presence of norepinephrine, and the melatonin content, was quantified. The expression of glutamate receptors, the intracellular calcium content and the NF-κB activation were analyzed in astrocytes and pinealocytes. TNF-α's possible mediation of the effect of glutamate was also investigated. The results showed that glutamate's inhibitory effect on melatonin synthesis involves interactions between astrocytes and pinealocytes, possibly through the release of TNF-α. Moreover, the activation of the astrocytic NF-κB seems to be a necessary step. In astrocytes and pinealocytes, AMPA, NMDA, and group I metabotropic glutamate receptors were observed, as well as the intracellular calcium elevation. In conclusion, there is evidence that the modulation of melatonin synthesis by glutamate involves paracrine interactions between pinealocytes and astrocytes through the activation of the astrocytic NF-κB transcription factor and possibly by subsequent TNF-αrelease.


1998 ◽  
Vol 63 (7) ◽  
pp. 1031-1044 ◽  
Author(s):  
Michal Hoskovec ◽  
Oldřich Hovorka ◽  
Blanka Kalinová ◽  
Bohumír Koutek ◽  
Aleš Svatoš ◽  
...  

New analogues of (Z)-dodec-8-en-1-yl acetate (Z8-12:OAc, 1), the main sex pheromone component of the Oriental fruit moth, Cydia molesta, were designed by formally transferring the terminal propyl group from the C-9 to the C-7 position to form vinyl-branched (2, 3) or, after isomerization, ethylidene-branched (4) structures and by replacing the -CH=CH- grouping by the -S-CH2- moiety (5, 6). Their biological activities were studied both electrophysiologically and behaviourally (laboratory mating and wind tunnel experiments). All the structural modifications resulted in analogues whose electroantennographic activities were lower than that of 1 following the order 1 >> 6 ≈ 5 >> 2 ≈ 4 ≈ 3. The single sensillum recording activities indicated that all the analogues stimulate the same Z8-12:OAc receptor neurone. In behavioural experiments, the analogues were generally found to reduce the ability of males to find a pheromone source, however, to different degrees. The highest inhibitory effect (90%) was observed for the thia analogues 5 and 6. The results support the view that the inhibitory properties of the analogues should not be entirely associated with their pheromone-mimicking capabilities.


Author(s):  
Maryam Hosseini ◽  
Wanqiu Chen ◽  
Charles Wang

The pandemic of novel coronavirus disease 2019 (COVID-19) is rampaging the world with more than 1.4 million of confirmed cases and more than 85,000 of deaths across world by April 9th, 2020. There is an urgent need to identify effective drugs to fight against the virus. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the family of coronaviruses consisting of four structural and 16 non-structured proteins. Three non-structural proteins such as main protease, papain like protease, and RNA-dependent RNA polymerase are believed to play a crucial role in the virus replication. We applied a computational ligand-receptor binding modeling and performed a comprehensive virtual screening on the FDA-approved drugs against these three SARS-CoV-2 proteins using AutoDock Vina. Our computational studies indicated that Simeprevir, Ledipasvir, Idarubicin, Saquinavir, Ledipasivir, Partitaprevir, Glecaprevir, and Velpatasvir are all promising inhibitors, which displayed a lower binding energy (higher inhibitory effect) than Remdesivir, Lopinavir, and Ritonavir. However, we found that chloroquine and hydroxychloroquine, which showed efficacy in treating the COVID-19 in recent clinical studies, had high binding energy with all three proteins, suggesting they may work through a different mechanism. We also identified several novel drugs as potential inhibitors against SARS-CoV-2, including antiviral Raltegravir; antidiabetic Amaryl; antibiotics Retapamulin, Rifimixin, and Rifabutin; antiemetic Fosaprepitant and Netupitant. In summary, our computational molecular docking approach and virtual screening identified some promising candidate SARS-CoV-2 drugs that may be considered for further clinical studies.


Planta Medica ◽  
2021 ◽  
Author(s):  
Thi Thu Ha Nguyen ◽  
Zhao Qu ◽  
Van Tuyen Nguyen ◽  
Thanh Tra Nguyen ◽  
Thi Tu Anh Le ◽  
...  

Three prenylated xanthones, garcinone E (1), bannaxanthone D (2) and bannanxanthone E (3) were isolated from the leaves of Garcinia mckeaniana Graib. Their structures were elucidated by spectral methods and compared with literature data. To evaluate their anti-proliferative effects in tumor cells, firstly, cisplatin was used as a positive control and the effects of compound 1-3 were determined by performing MTT assay in MDA-MB-231, CNE-2 and A549 cancer cells. The results showed compound 1-3 exhibited stronger inhibitory effect than cisplatin in MDA-MB-231. Further effects of compound 1-3 in TNBC MDA-MB-231 and MDA-MB-468 cells were examined by performing cell cycle and apoptosis assays. The results indicated that compound 1-3 had ability to arrest cell cycle at G2/M phase and induce apoptosis. Furthermore, compound 2 significantly down-regulated PI3K, Akt and mTOR levels in both total proteins and phosphorylated form, which is its potential anti-cancer mechanism. These findings indicated that those prenylated xanthones might serve as promising leading compounds for the development of anticancer drug for TNBC.


2004 ◽  
Vol 83 (4) ◽  
pp. 278-282 ◽  
Author(s):  
N. Bouropoulos ◽  
J. Moradian-Oldak

Extracellular matrix proteins are considered to play essential roles in controlling the nucleation, growth, and organization of hydroxyapatite crystals during enamel formation. The effects of amelogenin and the 32-kDa enamelin proteins on apatite nucleation were investigated by a steady-state gel diffusion device containing 10% gelatin gels loaded with 0, 0.75%, and 1.5% (w/w) native porcine amelogenins. It was found that the induction time for hydroxyapatite precipitation was strongly increased by the presence of amelogenins, suggesting an inhibitory effect of apatite nucleation. Addition of 18 μg/mL of 32-kDa enamelin to 10% gelatin also caused inhibition of nucleation. Remarkably, addition of 18 and 80 μg/mL of 32-kDa enamelin in gels containing 1.5% amelogenin accelerated the nucleation process in a dose-dependent manner. Our observations strongly suggest that the 32-kDa enamelin and amelogenins cooperate to promote nucleation of apatite crystals and propose a possible novel mechanism of mineral nucleation during enamel biomineralization.


Plant Disease ◽  
2001 ◽  
Vol 85 (4) ◽  
pp. 436-441 ◽  
Author(s):  
K. D. Cox ◽  
H. Scherm

Pseudosclerotia (infected, mummified fruit) are the only source of primary inoculum of Monilinia vaccinii-corymbosi, the causal agent of mummy berry disease of blueberry. Laboratory applications of potential inhibitors of carpogenic germination were made to pseudosclerotia at three distinct developmental stages, i.e., ungerminated pseudosclerotia, pseudosclerotia with emerging stipes, and those with mature apothecia. Potential inhibitors evaluated included soybean oil and ammonium thiosulfate (two desiccants used experimentally as bloom thinners in fruit crops) and diuron and simazine (two commonly used herbicides), each applied in an aqueous suspension with 3% Latron B-1956 surfactant. Various aspects of carpogenic germination including the percentage of pseudosclerotia that produced stipes or apothecia, the number of stipes or apothecia per pseudosclerotium, the percentage of stipes that developed into apothecia, longevity of stipes and apothecia, and ascospore numbers were assessed. Compared with water, application of ammonium thiosulfate (2%) and diuron (2%) reduced stipe and apothecium production when sprayed on ungerminated pseudosclerotia, but these reductions were generally not significantly different from those achieved with Latron B applied alone (P > 0.05). The two compounds, however, completely inhibited the development of stipes into apothecia when applied to pseudosclerotia with stipes and caused a >3-fold reduction in apothecium longevity when applied to pseudosclerotia with mature apothecia. Application of simazine (2%) before germination or at stipe emergence resulted in the development of malformed apothecia from which no ascospores were recovered; stipe and apothecium longevity were also reduced. Soybean oil (15%) and Latron B applied alone had weak or inconsistent effects on most aspects of carpogenic germination of pseudosclerotia, although both compounds, when applied at stipe emergence, significantly reduced ascospore numbers in subsequently formed apothecia. The results suggest that diuron and simazine applied for weed control in commercial blueberry plantings may have beneficial side effects in reducing carpogenic germination of pseudosclerotia. The strong inhibitory effect of ammonium thiosulfate on all aspects of carpogenic germination, along with its value as a nitrogen fertilizer and ancillary herbicide, warrants further evaluation of this compound's performance and economics in the field.


2002 ◽  
Vol 68 (10) ◽  
pp. 5012-5016 ◽  
Author(s):  
S. A. Keçeli ◽  
R. J. Miles

ABSTRACT The energy-generating pathways of Mycoplasma spp. are diverse. Thus, it was predicted that the ability of inhibitors of these pathways to block growth would vary among species. This prediction was tested with 14 Mycoplasma species and potential inhibitors. The greatest differentiation among test species was obtained using fluoride, iodoacetate (IAA), β-fluoropyruvate (FP), cibacron blue (CB), l-citrulline, and carbonyl cyanide m-chlorophenylhydrazone. A range of other potential inhibitors, including l-arginine analogues, had little inhibitory effect on growth, and d-arginine was shown to be a growth substrate for arginine-hydrolyzing species. Fluoride selectively inhibited the growth of mycoplasmas that were able only to ferment sugars to lactate and/or to hydrolyze arginine. In contrast, IAA was most effective against organic acid-oxidizing species, and l-citrulline inhibited arginine-hydrolyzing species. Mycoplasma verecundum, a species for which energy sources have not been identified, was relatively resistant to FP. Similarly, Acholeplasma laidlawii was distinguished by its CB resistance.


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