scholarly journals In vitro and in vivo Effects of a Single Dose of Bupivacaine 5% on Donkey Chondrocytes

2021 ◽  
Vol 8 ◽  
Author(s):  
Kamal Hussein ◽  
Abdelbaset Eweda Abdelbaset ◽  
Ahmed Abdelrahiem Sadek ◽  
Ahmed Noreldin
Keyword(s):  
Histopathological Examination ◽  
Quantitative Polymerase Chain Reaction ◽  
Cartilage Damage ◽  
Arthroscopic Surgery ◽  
Time Points ◽  
Healthy Adult Male ◽  
Carpal Joint ◽  
Long Acting

Single intra-articular (IA) injection of long-acting local anesthetics such as bupivacaine is commonly used clinically for postoperative analgesia, in particular, after arthroscopic surgery. Despite their widespread use, the side effects of IA bupivacaine on joint cartilage as well as hepatotoxic and nephrotoxic effects remain to be elucidated. The aim of this study is to assess the in vitro effect of bupivacaine 5% on donkey chondrocytes at different time points, in addition to the in vivo effects of a single IA bupivacaine injection on the middle carpal joint in a group of 10 clinically healthy adult male donkeys. In phase I, the effect of in vitro treatment with bupivacaine 5% or saline 0.9% on freshly isolated donkey chondrocytes for 30, 60 min, 24, 48, and 96 h was investigated using MTT and LIVE/DEAD assay. In phase II, in vivo effects of single injection of bupivacaine on the middle carpal joint of the donkey were evaluated compared with saline 0.9%. Biochemical analysis of collected serum and synovia was performed. Additionally, articular cartilage damage was evaluated using radiography, computed tomography (CT), catabolic marker expression via quantitative polymerase chain reaction (qPCR), and histopathological examination 96 h after injection. Our results showed that after a 30-min exposure to bupivacaine 5%, the viability of donkey chondrocytes was 97.3 ± 4.4% and was not significantly affected at the indicated time points (n = 8, p < 0.05). No significant changes in biochemical analytes of serum and synovial fluid following IA bupivacaine injection were observed, compared with saline injection (n = 5 for each group, p < 0.05). Furthermore, in vivo IA injection of bupivacaine revealed no significant differences in radiography, CT scan, gene expression of cartilage catabolic biomarkers, and histopathological examination. These results provide an evidence for the safety of bupivacaine on the donkey cartilage.

A novel long-acting, follicle stimulating hormone-Fc fusion protein displays Gonal-f-like function in vitro and in vivo

2021 ◽  
Author(s):  
Guili XU ◽  
Yi Yang ◽  
Yunhui Liu ◽  
Fang Chen ◽  
Lihou Dong ◽  
...  
Keyword(s):  
Follicle Stimulating Hormone ◽  
Fallopian Tubes ◽  
Ovarian Weight ◽  
Time Points ◽  
Sd Rats ◽  
Expression Of Genes ◽  
Fc Fusion Protein ◽  
Long Acting

Abstract Purpose To explore whether X002 can enhance bioactivity and has a long half-time in vitro and in vivo. Methods For the in vitro study, GVBD rate and COC expansion were applied. In the GVBD test, 21–24-day-old female KM mice were stimulated with PMSG for 46 h, and the naked oocytes of ovaries were then collected. Four hours after X002 treatment at 37℃, the GVBD rates of naked oocytes were counted. In COC expansion, COCs were collected from mice stimulated with PMSG. After coculture of COCs and X002 for 14 h, COC diameter was measured, and the expression of genes involved in COC expansion was also determined by RT-qPCR. For the in vivo study, 6–8-week-old female SD rats were administered a subcutaneous injection of X002 for pharmacokinetics. Serum was assayed by ELISA at different time points. For pharmacodynamics, 26-day-old female SD rats were used in ovarian weight and superovulation assay. To assay ovarian weight, rats were stimulated with hCG 84 h after X002 treatment. At 12 h after hCG injection, ovaries were weighted and E2 or P4 in serum was quantified. To assay superovulation, rats were treated with the above methods. At 108 h after X002 treatment, oocytes were counted from fallopian tubes. Results X002 promoted GVBD and COC expansion in vitro and effectively promoted significant ovarian weight gain and superovulation, similar to Gonal-f; Meanwhile, it had a longer T1/2. Conclusions X002 is a long-acting FSH-liked agent which has good bioactivity, similar to Gonal-f.

THYROID STIMULATORS AND THYROID STIMULATION

1971 ◽  
Vol 66 (3) ◽  
pp. 558-576 ◽  
Author(s):  
Gerald Burke
Keyword(s):  
Regulatory System ◽  
Control Site ◽  
Thyroid Cell ◽  
Primary Control ◽  
Physico Chemical ◽  
Site Of Action ◽  
Long Acting

ABSTRACT A long-acting thyroid stimulator (LATS), distinct from pituitary thyrotrophin (TSH), is found in the serum of some patients with Graves' disease. Despite the marked physico-chemical and immunologic differences between the two stimulators, both in vivo and in vitro studies indicate that LATS and TSH act on the same thyroidal site(s) and that such stimulation does not require penetration of the thyroid cell. Although resorption of colloid and secretion of thyroid hormone are early responses to both TSH and LATS, available evidence reveals no basic metabolic pathway which must be activated by these hormones in order for iodination reactions to occur. Cyclic 3′, 5′-AMP appears to mediate TSH and LATS effects on iodination reactions but the role of this compound in activating thyroidal intermediary metabolism is less clear. Based on the evidence reviewed herein, it is suggested that the primary site of action of thyroid stimulators is at the cell membrane and that beyond the(se) primary control site(s), there exists a multifaceted regulatory system for thyroid hormonogenesis and cell growth.

scholarly journals Long-Acting Risperidone Dual Control System: Preparation, Characterization and Evaluation In Vitro and In Vivo

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1210
Author(s):  
Xieguo Yan ◽  
Shiqiang Wang ◽  
Kaoxiang Sun
Keyword(s):  
Drug Loading ◽  
Entrapment Efficiency ◽  
In Vitro Dissolution ◽  
Dissolution Behavior ◽  
In Vivo Evaluation ◽  
Long Term Treatment ◽  
Long Acting

Schizophrenia, a psychiatric disorder, requires long-term treatment; however, large fluctuations in blood drug concentration increase the risk of adverse reactions. We prepared a long-term risperidone (RIS) implantation system that can stabilize RIS release and established in-vitro and in-vivo evaluation systems. Cumulative release, drug loading, and entrapment efficiency were used as evaluation indicators to evaluate the effects of different pore formers, polymer ratios, porogen concentrations, and oil–water ratios on a RIS implant (RIS-IM). We also built a mathematical model to identify the optimized formulation by stepwise regression. We also assessed the crystalline changes, residual solvents, solubility and stability after sterilization, in-vivo polymer degradation, pharmacokinetics, and tissue inflammation in the case of the optimized formulation. The surface of the optimized RIS microspheres was small and hollow with 134.4 ± 3.5 µm particle size, 1.60 SPAN, 46.7% ± 2.3% implant drug loading, and 93.4% entrapment efficiency. The in-vitro dissolution behavior of RIS-IM had zero-order kinetics and stable blood concentration; no lag time was released for over three months. Furthermore, the RIS-IM was not only non-irritating to tissues but also had good biocompatibility and product stability. Long-acting RIS-IMs with microspheres and film coatings can provide a new avenue for treating schizophrenia.

scholarly journals Development of In Situ Self-Assembly Nanoparticles to Encapsulate Lopinavir and Ritonavir for Long-Acting Subcutaneous Injection

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 904
Author(s):  
Irin Tanaudommongkon ◽  
Asama Tanaudommongkon ◽  
Xiaowei Dong
Keyword(s):  
Sustained Release ◽  
Trough Concentration ◽  
Self Assembly ◽  
Subcutaneous Injection ◽  
Drug Loading ◽  
Entrapment Efficiency ◽  
Long Acting

Most antiretroviral medications for human immunodeficiency virus treatment and prevention require high levels of patient adherence, such that medications need to be administered daily without missing doses. Here, a long-acting subcutaneous injection of lopinavir (LPV) in combination with ritonavir (RTV) using in situ self-assembly nanoparticles (ISNPs) was developed to potentially overcome adherence barriers. The ISNP approach can improve the pharmacokinetic profiles of the drugs. The ISNPs were characterized in terms of particle size, drug entrapment efficiency, drug loading, in vitro release study, and in vivo pharmacokinetic study. LPV/RTV ISNPs were 167.8 nm in size, with a polydispersity index of less than 0.35. The entrapment efficiency was over 98% for both LPV and RTV, with drug loadings of 25% LPV and 6.3% RTV. A slow release rate of LPV was observed at about 20% on day 5, followed by a sustained release beyond 14 days. RTV released faster than LPV in the first 5 days and slower than LPV thereafter. LPV trough concentration remained above 160 ng/mL and RTV trough concentration was above 50 ng/mL after 6 days with one subcutaneous injection. Overall, the ISNP-based LPV/RTV injection showed sustained release profiles in both in vitro and in vivo studies.

scholarly journals Development of Triamcinolone Acetonide-Loaded Microemulsion as a Prospective Ophthalmic Delivery System for Treatment of Uveitis: In Vitro and In Vivo Evaluation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 444
Author(s):  
Alaa Mahran ◽  
Sayed Ismail ◽  
Ayat A. Allam
Keyword(s):  
Triamcinolone Acetonide ◽  
Delivery System ◽  
Histopathological Examination ◽  
Rabbit Model ◽  
Subconjunctival Injection ◽  
In Vivo Evaluation ◽  
Ternary Phase Diagrams ◽  
Ophthalmic Delivery

Treatment of uveitis (i.e., inflammation of the uvea) is challenging due to lack of convenient ophthalmic dosage forms. This work is aimed to determine the efficiency of triamcinolone acetonide (TA)-loaded microemulsion as an ophthalmic delivery system for the treatment of uveitis. Water titration method was used to construct different pseudo-ternary phase diagrams. Twelve microemulsion formulations were prepared using oleic acid, Cremophor EL, and propylene glycol. Among all tested formulations, Formulation F3, composed of oil: surfactant-co-surfactant (1:1): water (15:35:50% w/w, respectively), was found to be stable and showed acceptable pH, viscosity, conductivity, droplet size (211 ± 1.4 nm), and zeta potential (−25 ± 1.7 mV) and almost complete in vitro drug release within 24 h. The in vivo performance of the optimized formulation was evaluated in experimentally uveitis-induced rabbit model and compared with a commercial TA suspension (i.e., Kenacort®-A) either topically or by subconjunctival injection. Ocular inflammation was evaluated by clinical examination, white blood cell count, protein content measurement, and histopathological examination. The developed TA-loaded microemulsion showed superior therapeutic efficiency in the treatment of uveitis with high patient compliance compared to commercial suspension. Hence, it could be considered as a potential ocular treatment option in controlling of uveitis.

scholarly journals Akt kinase LANCL2 functions as a key driver in EGFR-mutant lung adenocarcinoma tumorigenesis

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Yuqing Lou ◽  
Jianlin Xu ◽  
Yanwei Zhang ◽  
Wei Zhang ◽  
Xueyan Zhang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cell Line ◽  
Quantitative Polymerase Chain Reaction ◽  
Mutant Cell ◽  
A549 Cells ◽  
The Cancer Genome Atlas ◽  
Akt Kinase ◽  
Egfr Expression

AbstractEpidermal growth factor receptor (EGFR) is a key oncogene in lung adenocarcinoma (LUAD). Resistance to EGFR tyrosine kinase inhibitors is a major obstacle for EGFR-mutant LUAD patients. Our gene chip array, quantitative polymerase chain reaction validation, and shRNA-based high-content screening identified the Akt kinase lanthionine synthetase C-like protein 2 (LANCL2) as a pro-proliferative gene in the EGFR-mutant LUAD cell line PC9. Therefore, we investigated whether LANCL2 plays a role in promoting cell proliferation and drug resistance in EGFR-mutant LUAD. In silico clinical correlation analysis using the Cancer Genome Atlas Lung Adenocarcinoma dataset revealed a positive correlation between LANCL2 and EGFR expression and an inverse relationship between LANCL2 gain-of-function and survival in LUAD patients. The EGFR-mutant LUAD cell lines PC9 and HCC827 displayed higher LANCL2 expression than the non-EGFR-mutant cell line A549. In addition, LANCL2 was downregulated following gefitinib+pemetrexed combination therapy in PC9 cells. LANCL2 knockdown reduced proliferation and enhanced apoptosis in PC9, HCC827, and A549 cells in vitro and suppressed murine PC9 xenograft tumor growth in vivo. Notably, LANCL2 overexpression rescued these effects and promoted gefitinib + pemetrexed resistance in PC9 and HCC827 cells. Pathway analysis and co-immunoprecipitation followed by mass spectrometry of differentially-expressed genes in LANCL2 knockdown cells revealed enrichment of several cancer signaling pathways. In addition, Filamin A and glutathione S-transferase Mu 3 were identified as two novel protein interactors of LANCL2. In conclusion, LANCL2 promotes tumorigenic proliferation, suppresses apoptosis, and promotes gefitinib+pemetrexed resistance in EGFR-mutant LUAD cells. Based on the positive association between LANCL2, EGFR, and downstream Akt signaling, LANCL2 may be a promising new therapeutic target for EGFR-mutant LUAD.

scholarly journals Discovery of novel mechanosensitive genes in vivo using mouse carotid artery endothelium exposed to disturbed flow

Blood ◽  
2010 ◽  
Vol 116 (15) ◽  
pp. e66-e73 ◽  
Author(s):  
Chih-Wen Ni ◽  
Haiwei Qiu ◽  
Amir Rezvan ◽  
Kihwan Kwon ◽  
Douglas Nam ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Ex Vivo ◽  
Expression Profiles ◽  
Quantitative Polymerase Chain Reaction ◽  
Gene Expression Profiles ◽  
Disturbed Flow ◽  
A Genome ◽  
Pattern Comparison

Abstract Recently, we showed that disturbed flow caused by a partial ligation of mouse carotid artery rapidly induces atherosclerosis. Here, we identified mechanosensitive genes in vivo through a genome-wide microarray study using mouse endothelial RNAs isolated from the flow-disturbed left and the undisturbed right common carotid artery. We found 62 and 523 genes that changed significantly by 12 hours and 48 hours after ligation, respectively. The results were validated by quantitative polymerase chain reaction for 44 of 46 tested genes. This array study discovered numerous novel mechanosensitive genes, including Lmo4, klk10, and dhh, while confirming well-known ones, such as Klf2, eNOS, and BMP4. Four genes were further validated for protein, including LMO4, which showed higher expression in mouse aortic arch and in human coronary endothelium in an asymmetric pattern. Comparison of in vivo, ex vivo, and in vitro endothelial gene expression profiles indicates that numerous in vivo mechanosensitive genes appear to be lost or dysregulated during culture. Gene ontology analyses show that disturbed flow regulates genes involved in cell proliferation and morphology by 12 hours, followed by inflammatory and immune responses by 48 hours. Determining the functional importance of these novel mechanosensitive genes may provide important insights into understanding vascular biology and atherosclerosis.

scholarly journals Diacerein-Loaded Hyaluosomes as a Dual-Function Platform for Osteoarthritis Management via Intra-Articular Injection: In Vitro Characterization and In Vivo Assessment in a Rat Model

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 765
Author(s):  
Nouran O. Abdelmageed ◽  
Nadia M. Morsi ◽  
Rehab N. Shamma
Keyword(s):  
Hyaluronic Acid ◽  
Cartilage Damage ◽  
Entrapment Efficiency ◽  
Dual Function ◽  
In Vitro Characterization ◽  
Drug Entrapment Efficiency ◽  
Formulation Parameters ◽  
Acid Gel

The application of intra-articular injections in osteoarthritis management has gained great attention lately. In this work, novel intra-articular injectable hyaluronic acid gel-core vesicles (hyaluosomes) loaded with diacerein (DCN), a structural modifying osteoarthritis drug, were developed. A full factorial design was employed to study the effect of different formulation parameters on the drug entrapment efficiency, particle size, and zeta potential. Results showed that the prepared optimized DCN- loaded hyaluosomes were able to achieve high entrapment (90.7%) with a small size (310 nm). The morphology of the optimized hyaluosomes was further examined using TEM, and revealed spherical shaped vesicles with hyaluronic acid in the core. Furthermore, the ability of the prepared DCN-loaded hyaluosomes to improve the in vivo inflammatory condition, and deterioration of cartilage in rats (injected with antigen to induce arthritis) following intra-articular injection was assessed, and revealed superior function on preventing cartilage damage, and inflammation. The inflammatory activity assessed by measuring the rat’s plasma TNF-α and IL-1b levels, revealed significant elevation in the untreated group as compared to the treated groups. The obtained results show that the prepared DCN-loaded hyaluosomes would represent a step forward in the design of novel intra articular injection for management of osteoarthritis.

Study on the Effects of Kuanxiong Aerosol on the Isolated Artery and Rabbits Acute Myocardial Ischemia Model

2021 ◽  
Vol 24 ◽  
Author(s):  
Xia Liu ◽  
Feihua Huang ◽  
Xiao Lu ◽  
Yuji Wang ◽  
Tingting Cai ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Troponin T ◽  
Pharmacological Study ◽  
Acute Myocardial Ischemia ◽  
Chinese Herbal Compound ◽  
Long Acting ◽  
Traditional Chinese Medicine Preparation ◽  
T Waves

Background: Kuan xiong aerosol (KXA) is a kind of Chinese herbal compound used to regulating qi-flowing for relieving pain and improving angina. However, little pharmacological study of this traditional Chinese medicine preparation has been reported to confirm these activities. Objective: This article aims to observe the effect of resisting acute myocardial ischemia (AMI) in vivo and dilating vessel in vitro of KXA. Materials: The AMI model involves intravenously injecting pituitary (2 U.kg-1) into the ear of rabbits. Electrocardiograph (ECG) T waves were then recorded after administration and the falling range was calculated. Following this, the level of serum Cardiac troponin T (cTn-T) and the histopathology of the cardiac muscle tissue was evaluated. In vitro, the effect of KXA on vasodilation of isolated aortic rings that had been pre-contracted with KCl (30 mM) was observed. Results: It was found KXA reduced ECG ST-T waves and serum cTn-T in the rabbit AMI model, protected myocardial tissue from fracturing and loss of myocardial fibers, and inhibited inflammatory cell infiltration, cavitation degeneration and karyopyknosis of the myocardial matrix. Furthermore, the administration of 0.215, 1.075 and 2.150 mg.mL-1 KXA resulted in significant relaxation of the aortic rings at a rate of 69.63 %, 90.14 % and 118.72 % (p < 0.01) of the untreated ones, and a second shrinkage ratio of 20.17 %, 4.29 %, and 4.54 % (p < 0.01) of the untreated ones, respectively. Conclusions: these results suggest KXA protects against AMI, contributes to dilation of blood vessels and has long-acting effectiveness.

scholarly journals Quercetin and Idebenone Ameliorate Oxidative Stress, Inflammation, DNA damage, and Apoptosis Induced by Titanium Dioxide Nanoparticles in Rat Liver

Dose-Response ◽  
2018 ◽  
Vol 16 (4) ◽  
pp. 155932581881218 ◽  
Author(s):  
Laila M. Fadda ◽  
Hanan Hagar ◽  
Azza M. Mohamed ◽  
Hanaa M. Ali
Keyword(s):  
Titanium Dioxide ◽  
Histopathological Examination ◽  
Titanium Dioxide Nanoparticles ◽  
Reactive Protein ◽  
Wide Range ◽  
Factor Α ◽  
Immunoglobin G ◽  
Endothelial Growth Factor

Titanium dioxide nanoparticles (TiO2-NPs) are extensively used in a wide range of applications; however, many reports have investigated their nanotoxicological effect at the molecular level either in vitro or in vivo systems. The defensive roles of quercetin (Qur) or idebenone (Id) against the hepatotoxicity induced by TiO2-NPs were evaluated in the current study. The results showed that the coadministration of Qur or Id to rats intoxicated with TiO2-NPs markedly ameliorated the elevation in hepatic malondialdehyde (MDA), serum alanine amino-transferase (ALT), glucose, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), immunoglobin G (IgG), and C-reactive protein (CRP) levels compared to their levels in TiO2-NPs-treated rats. The aforementioned antioxidants also effectively modulated the changes in the levels of serum vascular endothelial growth factor (VEGF), nitric oxide (NO), hepatic DNA breakage, caspase-3, and inhibition of drug metabolizing enzymes (cytochrome P450s; CYP4502E12E1) in rat livers induced by TiO2-NPs toxicity. The histopathological examination of the liver section showed that TiO2-NPs caused severe degeneration of most hepatocytes with an increase in collagen in the portal region, while treatment with the antioxidants in question improved liver architecture. These outcomes supported the use of Qur and Id as protective agents against the hepatotoxicity induced by TiO2-NPs and other hepatotoxic drugs.

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