Time- and dose-dependent digoxin redistribution by digoxin-specific antigen binding fragments in a rat model

AbstractPulmonary arterial hypertension (PAH) is a group of diseases with an increase of pulmonary artery pressure (PAP) and pulmonary vascular resistance. Here, the effects of safflower injection, a preparation of Chinese herbs, was investigated in a monocrotaline (MCT)-induced PAH rat model. PAP, carotid artery pressure (CAP), and the right ventricular hypertrophy index (RVHI) increased in the PAH group, while safflower injection was able to inhibit this increase to similar levels as observed in the normal group. The arteriole wall of the lungs and cardiac muscle were thickened and edema was observed in the PAH group, while these pathologies were improved in the herb-treated group in a dose-dependent manner. MCT treatment induced proliferation of pulmonary artery smooth muscle cells (PASMCs), which was inhibited by safflower injection in a dose-dependent manner. Our experimental results demonstrated that safflower injection can regulate pulmonary arterial remodeling through affecting the expression of connective tissue growth factor, transforming growth factor-β, integrin, collagen or fibronectin, which subsequently affected the thicknesses of the arteriole walls of the lungs and cardiac muscle, and thereby benefits the control of PAH. This means safflower injection improved the abnormalities in PAP, CAP and RVHI, and pulmonary arterial remodeling through regulation of remodeling factors.

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Synergistic Effect of Docetaxel Plus Saponin Fraction of Vitex doniana on Prostate Specific Antigen and p53 in Nitrsobis (2-oxopropyl) Amine-induced Prostate Toxicity

Journal of Applied Life Sciences International ◽

10.9734/jalsi/2021/v24i830253 ◽

2021 ◽

pp. 17-22

Author(s):

Ifeanacho Ezeteonu Abireh ◽

Godson Emeka Anyanwu

Keyword(s):

Synergistic Effect ◽

Prostate Specific Antigen ◽

Wistar Rats ◽

Specific Antigen ◽

P53 Expression ◽

Male Wistar Rats ◽

Saponin Fraction ◽

Vitex Doniana ◽

Dose Dependent ◽

Group 1

Aim: This study investigated the synergistic effect of docetaxel plus saponin fraction of Vitex doniana on prostate specific antigen and p53 in nitrsobis (2-oxopropyl) amine-induced prostate toxicity in Wistar rat. Methodology: Twenty-four (24) male Wistar rats with elevated serum prostate specific antigen level were selected from a group of sixty (60) rats pretreated with subcutaneous Nitrosobis (2-oxopropyl) amine 5 mg/kg daily for 4 weeks. The selected 24 male Wistar rats were then grouped into 6 groups of four (4) rats each. Group 1 was given 1ml normal saline daily from day 1-28. Groups 2, 3, 4, 5, and 6 further received subcutaneous nitrosobis (2-oxopropyl) amine 5 mg/kg daily from day 1-28. In addition, groups 3, 4, 5, and 6 were given weekly intravenous docetaxel 8 mg/kg on day 15 and 22. In addition to docetaxel, groups 4, 5, and 6 were further treated with oral saponin at 250 mg/kg, 500 mg/kg, and 750 mg/kg, respectively, daily, from day 15-28. Immunoenzymometric assay method was used for analysis of blood sample for prostate specific antigen. The prostate tissues were subjected to immuno study using the ImmunoCruz Staining System (Lab Vision Corporation, Fremont, CA, USA). The quantitative evaluation of p53 was done by calculating the percentages of p53-immunostained nuclei (labeling index). Results: Significant increase in prostate specific antigen and p53 expression were observed in group 2 (treated with Nitrsobis (2-oxopropyl) amine alone) when compared with group 1 (control). Dose dependent decrease in prostate specific antigen and p53 expression were observed in groups 4, 5, and 6, treated with docetaxel 8 mg/kg plus 250 mg/kg, 500 mg/kg, and 750 mg/kg of saponin respectively. Conclusion: Docetaxel plus Saponin fraction of Vitex doniana significantly reduced the serum prostate specific antigen concentration and p53 expression in a dose dependent manner, with the group treated with 750 mg/kg showing the highest decrease in the parameters tested.

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Therapeutic effect and mechanism of action of quercetin in a rat model of osteoarthritis

Journal of International Medical Research ◽

10.1177/0300060519873461 ◽

2019 ◽

Vol 48 (3) ◽

pp. 030006051987346 ◽

Cited By ~ 1

Author(s):

Jun Zhang ◽

Jing Yin ◽

Daohong Zhao ◽

Chaoran Wang ◽

Yuhao Zhang ◽

...

Keyword(s):

Therapeutic Effect ◽

Mechanism Of Action ◽

Rat Model ◽

Dependent Manner ◽

Nuclear Factor ◽

Toll Like Receptor ◽

Tnf Α ◽

Dose Dependent ◽

Light Chain Enhancer ◽

Necrosis Factor

Objective To study the therapeutic effect and mechanism of action of quercetin in a rat model of osteoarthritis (OA). Methods The OA rat model was established by intra-articular injection of papain. Changes in knee diameter, toe volume and histopathology were measured. Levels of interleukin (IL)-β and tumor necrosis factor (TNF)-α were assessed by ELISA. Relative expression of Toll-like receptor (TLR)-4 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) was evaluated by western blotting. Results Compared with rats treated with papain alone, changes in knee diameter, toe volume and Makin' s score were less apparent in OA rats treated with quercetin. Levels of serum IL-1β and TNF-α were also reduced in quercetin-treated OA rats. Expression of TLR-4 and NF-κB was significantly suppressed in a dose-dependent manner in quercetin-treated OA rats. Conclusion Quercetin exhibited a therapeutic effect in OA rats, which may be related to inhibition of IL-1β and TNF-α production via the TLR-4/NF-κB pathway.

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Metabonomic profiles reveal dose-dependent effects of Bu-Shen-Gu-Chi-Wan on the serum in experimental periodontitis of rat model

Journal of Ethnopharmacology ◽

10.1016/j.jep.2016.07.051 ◽

2016 ◽

Vol 193 ◽

pp. 248-254 ◽

Cited By ~ 1

Author(s):

J. Li ◽

H. Yang ◽

S. Meng ◽

J. Zhou ◽

Y. Ding

Keyword(s):

Rat Model ◽

Experimental Periodontitis ◽

Dose Dependent

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Relationship between Fc receptors, antigen-binding sites on T and B cells, and H-2 complex-associated determinants.

Journal of Experimental Medicine ◽

10.1084/jem.141.3.547 ◽

1975 ◽

Vol 141 (3) ◽

pp. 547-560 ◽

Cited By ~ 60

Author(s):

A Basten ◽

J F Miller ◽

R Abraham

Keyword(s):

T Cells ◽

B Cells ◽

Specific Antigen ◽

Fc Receptors ◽

Fc Receptor ◽

Antigen Binding ◽

T And B Cells ◽

Spleen Cells ◽

Fab Fragment ◽

Thymus Cells

The relationship between H-2 complex-associated determinants, Fc receptors, and specific antigen-recognition sites on T and B cells was examined by binding and functional assays. The Fc receptor was detected by radiolabeled immune complexes or aggregated human IgG. Both these reagents selectively bound to B cells, not to T cells. When spleen cells, from mice primed to several antigens, were exposed to highly substituted radioactive aggregates, their capacity to transfer both a direct and indirect plaque-forming cell response to these antigens was abrogated. Addition of B cells, but not of T cells, restored responsiveness. Complexed Ig binding to Fc receptors was prevented by pretreatment of mixed lymphoid cell populations with antisera directed against membrane components on the same cell (e.g., H-2) and on other cells (e.g., theta). The lack of specificity of inhibition was thought to be due to the formation on cell surfaces of antigen-antibody complexes which would then attach to the Fc receptor during the incubation precedure. Specific blockade of the Fc receptor during the incubation procedure. Specific blockade of the Fc receptor however occurred when B cells were pretreated with the Fab fragments of anti-H-2 antibody. This was demonstrated autoradiographically and by inhibition of aggregate-induced suicide. The blocking activity of ante-H-2 Fab was removed by absorption with spleen cells from thymectomized irradiated mice but not with thymus cells of appropriate specificity. This suggested that the antibodies involved had specificity for determinants on the B-cell membrane distinct from those coded by the K or D end of the H-2 complex, and either absent from, or poorly represented on, thymus cells. Specific antigen-induced suicide of B cells was achieved simply by incubating the cells with radioactive antigen in the cold. T-cell suicide on the other hand required that the 125I-labeled antigen be presented to the T cells at 37 degrees-C on the surface of spleen cells from antigen-primed mice. Pretreatment of T cells with the Fab fragment of anti-H-2 antibody protected them from the suicide effect. By contrast no such protection of B cells could be achieved by this procedure. In other words H-2 (? Ir)-associated determinants may not only be in close proximity to the antigen-binding site on T cells but, in addition, may be involved in the effective operation of the receptor.

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Substituting Citrate for Lactate in Peritoneal Dialysis Fluid Improves Ultrafiltration in Rats

Peritoneal Dialysis International ◽

10.1177/089686080902900106 ◽

2009 ◽

Vol 29 (1) ◽

pp. 36-43 ◽

Cited By ~ 5

Author(s):

Nicola Cavallini ◽

Anders Wieslander ◽

Magnus Braide

Keyword(s):

Peritoneal Dialysis ◽

Peritoneal Cavity ◽

Rat Model ◽

Indwelling Catheter ◽

Citrate Concentration ◽

Peritoneal Dialysis Fluid ◽

Short Time ◽

Dose Dependent Increase ◽

Kinetics Of ◽

Dose Dependent

Background Exposure to peritoneal dialysis (PD) fluid induces an inflammatory response in the peritoneal cavity. Blockers of complement and coagulation have improved ultrafiltration in animal models of PD. Citrate is a clinically established anticoagulant that also blocks complement activation. Objective The aim of the present study was to evaluate the effects on ultrafiltration of a gradual substitution of citrate for lactate in an experimental model of PD. Methods Fractions (0, 5, 10, and 15 mmol/L) of the 40 mmol/L lactate buffer of filter-sterilized 2.5% glucose PD fluid were replaced by citrate. The modified fluids were compared in a rat model of single PD fluid exposure through an indwelling catheter. The initial kinetics of citrate and ionized calcium were evaluated in separate, single, short time dwell experiments. Results Replacing 10 and 15 mmol/L of the lactate buffer by sodium citrate significantly increased osmotic ultrafiltration (by 24.7% ± 7.7% at 10 mmol/L), net ultrafiltration, and glucose retention at 4 hours of dwell time in the rat model. Osmotic ultrafiltration was significantly correlated to citrate concentration and glucose concentration. Citrate was rapidly eliminated from the peritoneal cavity, concentrations falling to less than half in 1 hour and concentrations of calcium ions concomitantly normalized. Conclusions Substituting citrate for lactate induced a dose-dependent increase in ultrafiltration. Mechanisms probably involve the relation between diffusion and ultrafiltration, leading to increased glucose retention. The increase in ultrafiltration was quantitatively important at a citrate concentration (10 mmol/L) that is compatible with clinical applications of citrate.

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A Novel Fabrication of Dose-Dependent Injectable Curcumin Biocomposite Hydrogel System Anesthetic Delivery Method for Care and Management of Musculoskeletal Pain

Dose-Response ◽

10.1177/1559325820929555 ◽

2020 ◽

Vol 18 (3) ◽

pp. 155932582092955

Author(s):

Xuehong Jiang ◽

Shuaishuai Wang ◽

Hui Chen

Keyword(s):

Electron Microscopy ◽

Musculoskeletal Pain ◽

Rat Model ◽

Chronic Constriction Injury ◽

Chronic Musculoskeletal Pain ◽

Delivery Method ◽

Social Components ◽

Dose Dependent ◽

Remarkable Reduction

Chronic musculoskeletal pain has biological, psychological, and social components. In this article, we have demonstrated the easily injectable nanocomposite carrier for the treatment of chronic musculoskeletal pain. Briefly, the curcumin (Cur) loaded with lipid nanocapsules (LNCs; Cur@LNCs) using the phase invasion method. The synthesized Cur@LNCs were characterized by using scanning electron microscopy, transmittance electron microscopy, and the size of the fabricated nanoparticles confirmed by dynamic light scattering analysis. The synthesized Cur@LNC injectable hydrogel shows excellent results in vivo in the rat model. We have examined the efficiency of the chronic constriction injury in the rat model and induced the pain using thermal paw withdrawal latency. The injectable hydrogels Cur@LNCs display a remarkable reduction in pain 7 days post administrations compared to the untreated group animals. This work could establish the preclinical candidate of the neuropathic pain response in the future.

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