Effects of phytanic acid on the vitamin E status, lipid composition and physical properties of retinal cell membranes: implications for adult Refsum disease

2001 ◽  
Vol 101 (6) ◽  
pp. 697-705 ◽  
Author(s):  
S.P. YOUNG ◽  
A.W. JOHNSON ◽  
D.P.R. MULLER
Keyword(s):  
Vitamin E ◽  
Phytanic Acid ◽  
Retinal Cell ◽  
Physical Parameters ◽  
Refsum Disease ◽  
Membrane Composition ◽  
Complex Situation ◽  
Retinal Cells ◽  
Membrane Function

Adult Refsum disease is an inherited disorder in which phytanic acid accumulates in tissues and serum. Two hypotheses have been proposed to explain the pathogenesis of this condition. The molecular distortion hypothesis suggests that phytanic acid may alter membrane composition and structure, thereby affecting membrane function(s). The anti-metabolite hypothesis suggests that an accumulation of phytanic acid in membranes may interfere with vitamin E function. These two hypotheses were investigated by studying the effects of modulating phytanic acid and α-tocopherol concentrations on the fatty acid composition and certain physical parameters of cultured retinal cells. Results showed that (a) the phospholipid fraction of retinal cells readily incorporated phytanic acid, (b) the incorporation of phytanic acid increased membrane fluidity, (c) there was no competition for uptake between phytanic acid and α-tocopherol, and (d) the incorporation of phytanic acid did not increase the susceptibility of membranes to lipid peroxidation in vitro. These results obtained with cultured retinal cells suggest that the molecular distortion hypothesis, but not the anti-metabolite hypothesis, could explain the pathogenesis of adult Refsum disease. In vitro tissue culture models can, however, only approximate to the much more complex situation that occurs in vivo.

scholarly journals Immunocytochemical Profiling of Cultured Mouse Primary Retinal Cells

2017 ◽  
Vol 65 (4) ◽  
pp. 223-239 ◽  
Author(s):  
Marina C. Zalis ◽  
Sebastian Johansson ◽  
Ulrica Englund-Johansson
Keyword(s):  
Cell Cultures ◽  
Structural Information ◽  
Expression Profiles ◽  
Retinal Cell ◽  
Research Translation ◽  
Specific Cell ◽  
Retinal Cells ◽  
Cellular Expression

Primary retinal cell cultures and immunocytochemistry are important experimental platforms in ophthalmic research. Translation of retinal cells from their native environment to the in vitro milieu leads to cellular stress, jeopardizing their in vivo phenotype features. Moreover, the specificity and stability of many retinal immunochemical markers are poorly evaluated in retinal cell cultures. Hence, we here evaluated the expression profile of 17 retinal markers, that is, recoverin, rhodopsin, arrestin, Chx10, PKC, DCX, CRALBP, GS, vimentin, TPRV4, RBPMS, Brn3a, β-tubulin III, NeuN, MAP2, GFAP, and synaptophysin. At 7 and 18 days of culture, the marker expression profiles of mouse postnatal retinal cells were compared with their age-matched in vivo retinas. We demonstrate stable in vitro expression of all markers, except for arrestin and CRALBP. Differences in cellular expression and location of some markers were observed, both over time in culture and compared with the age-matched retina. We hypothesize that these differences are likely culture condition dependent. Taken together, we suggest a thorough evaluation of the antibodies in specific culture settings, before extrapolating the in vitro results to an in vivo setting. Moreover, the identification of specific cell types may require a combination of different genes expressed or markers with structural information.

scholarly journals Neurosphere-Free Trans-Differentiation of Rat Bone Marrow Stromal Stem Cells Into Retinal Cells and Retinal Pigment Epithelium

2021 ◽  
Author(s):  
Hamid AboutalebKadkhodaeian ◽  
◽  
Hamidreza Sameni ◽  
Ali Shahbazi ◽  
◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Retinal Pigment Epithelium ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Morphological Differentiation ◽  
Single Step ◽  
Retinal Cell ◽  
Retinal Cells

Purpose of study: Neurosphere-free trans-differentiation of bone marrow stem cells (NFT-BMSCs) into retinal pigment epithelium (RPE) and retinal cells (RCs) in vitro could offer a unique opportunity for the study of cell-replacement in degenerative eye diseases. In this respect, a simple, and efficient protocol for getting retinal cells from trans-differentiation of rat BMSCs in the neurosphere-free state are reported. Methods: Extracted BMSCs from hooded pigment rats were exposed to a single-step protocol, including neurosphere-free, containing a cocktail medium which induced trans-differentiation into retinal pigment epithelium (RPE) and retinal cells. Results: The results showed morphological differentiation changes in vitro. Also, expressed retinal pigment epithelium and retinal cell markers such as Otx2 (23.45%), RPE65 (91.54%), CRALBP (91.21%), VEGF (94.79%), Rhodopsin (57.19%), GFAP (28.33%), and NF200 (24.55%). Conclusion: Overall, these findings showed a protocol, without using bFGF, EGF, and B-27 supplement which makes it possible to obtain RPE and retinal cells in vitro.

1120: Citrate and Vitamin E Blunt the SWL-Induced Free Radical Surge in an In-Vitro MDCK Cell Culture Model

2004 ◽  
Vol 171 (4S) ◽  
pp. 295-295
Author(s):  
Fernando C. Delvecchio ◽  
Ricardo M. Brizuela ◽  
Karen J. Byer ◽  
W. Patrick Springhart ◽  
Saeed R. Khan ◽  
...  
Keyword(s):  
Cell Culture ◽  
Free Radical ◽  
Vitamin E ◽  
Mdck Cell ◽  
Cell Culture Model ◽  
Culture Model

Protective Effect of Vitamin E on Immune Triggered, Granulocyte Mediated Endothelial Injury

1984 ◽  
Vol 51 (01) ◽  
pp. 089-092 ◽  
Author(s):  
M A Boogaerts ◽  
J Van de Broeck ◽  
H Deckmyn ◽  
C Roelant ◽  
J Vermylen ◽  
...  
Keyword(s):  
Vitamin E ◽  
Protective Effect ◽  
Umbilical Vein ◽  
Endothelial Damage ◽  
Endothelial Injury ◽  
Mediated Effects ◽  
Anti Oxidant ◽  
Endothelial Cell Cultures ◽  
Vitro Model

SummaryThe effect of alfa-tocopherol on the cell-cell interactions at the vessel wall were studied, using an in vitro model of human umbilical vein endothelial cell cultures (HUEC). Immune triggered granulocytes (PMN) will adhere to and damage HUEC and platelets enhance this PMN mediated endothelial injury. When HUEC are cultured in the presence of vitamin E, 51Cr-leakage induced by complement stimulated PMN is significantly decreased and the enhanced cytotoxicity by platelets is completely abolished (p <0.001).The inhibition of PMN induced endothelial injury is directly correlated to a diminished adherence of PMN to vitamin E- cultured HUEC (p <0.001), which may be mediated by an increase of both basal and stimulated endogenous prostacyclin (PGI2) from alfa-tocopherol-treated HUEC (p <0.025). The vitamin E-effect is abolished by incubation of HUEC with the irreversible cyclo-oxygenase inhibitor, acetylsalicylic acid, but the addition of exogenous PGI2 could not reproduce the vitamin E-mediated effects.We conclude that vitamin E exerts a protective effect on immune triggered endothelial damage, partly by increasing the endogenous anti-oxidant potential, partly by modulating intrinsic endothelial prostaglandin production. The failure to reproduce vitamin E-protection by exogenously added PGI2 may suggest additional, not yet elucidated vitamin E-effects on endothelial metabolism.

Formulation and In-vitro Evaluation of Chewable Tablets of Montelukast Sodium

2015 ◽  
Vol 5 (3) ◽  
Author(s):  
Laxman Devkota ◽  
Bhupendra Poudel ◽  
Junu Silwal
Keyword(s):  
In Vitro Release ◽  
Magnesium Stearate ◽  
Physical Parameters ◽  
Artificial Sweetener ◽  
Leukotriene Receptor Antagonist ◽  
Montelukast Sodium ◽  
Chewable Tablets ◽  
Leukotriene Receptor ◽  
Vitro Release

The objective of the present study is to develop chewable tablets containing different pharmaceutical compositions with simple manufacturing procedures using different excipients. Mannitols, L-HPC 11, Aspartame, Crospovidone, Crospovidone, Aerosil, and Magnesium Stearate are used as excipients for effective formulation of anti-asthmatic drug Montelukast. Montelukast is a selective, orally acting leukotriene receptor antagonist that is used for the treatment of asthma and seasonal allergic rhinitis. Montelukast chewable tablets were prepared by Direct Compression methods using suitable excipients. The chewable tablets were better presented using artificial sweetener Aspartame as flavouring agent. A total of forteen formulations were prepared and the granules were evaluated for pre-compression parameters. The formulated tablets were evaluated for post-compression parameters .The results showed that all the physical parameters were within the acceptable limits. The in vitro release study of all the formulations showed good release. The study concludes that aforementioned excipients can be used to design chewable montelukast sodium tablets.

Preparation and Evaluation of Gemifloxacin Mesylate Floating Matrix Tablets in Healthy Human Volunteers

2017 ◽  
Vol 10 (1) ◽  
pp. 3623-3630
Author(s):  
Bhikshapathi D. V. R. N. ◽  
Haarika B ◽  
Jyothi Sri S ◽  
K Abbulu
Keyword(s):  
Drug Release ◽  
Sodium Bicarbonate ◽  
Polymer Concentration ◽  
Hydroxypropyl Methylcellulose ◽  
Matrix Tablets ◽  
Physical Parameters ◽  
Drug Bioavailability ◽  
Floating Tablets

The purpose of present investigation was to develop floating matrix tablets of gemifloxacin mesylate, which after oral administration could prolong the gastric residence time, increase the drug bioavailability and diminish the side effects of irritating drugs. Tablets containing drug, various viscosity grades of hydroxypropyl methylcellulose such as HPMC K4M and HPMC K15M as matrix forming agent, Sodium bicarbonate as gas-forming agent and different additives were tested for their usefulness in formulating gastric floating tablets by direct compression method. The physical parameters, in vitro buoyancy, release characteristics and in vivo radiographic study were investigated in this study. The gemifloxacin mesylate floating tablets were prepared using HPMC K4M polymer giving more sustained drug release than the tablet containing HPMC K15M. All these formulations showed floating lag time of 30 to 47 sec and total floating time more than 12 h. The drug release was decreased when polymer concentration increases and gas generating agent decreases. Formulation that contains maximum concen-tration of both HPMC K15M and sodium bicarbonate (F9) showing sufficiently sustained with 99.2% of drug release at 12 h. The drug release from optimized formulation follows Higuchi model that indicates the diffusion controlled release. The best formulation (F9) was selected based on in vitro characteristics and used in vivo radiographic studies by incorporating barium sulphate as a radio-opaque agent and the tablet remained in the stomach for about 6 h.   

Formulation and Evaluation of Immediate Release Bilayer Tablets of Telmisartan and Hydrochlorothiazide

2011 ◽  
Vol 4 (3) ◽  
pp. 1477-1483
Author(s):  
Natarajan R ◽  
N Patel ◽  
Rajendran N N ◽  
M Rangapriya
Keyword(s):  
Antihypertensive Drugs ◽  
In Vitro Release ◽  
Immediate Release ◽  
Wet Granulation ◽  
Physical Parameters ◽  
Dissolution Profile ◽  
Formulation Development ◽  
Sodium Starch Glycolate ◽  
Bilayer Tablets

The main goal of this study was to develop a stable formulation of antihypertensive drugs telmisartan and hydrochlorothiazide as an immediate-release bilayer tablet and to evaluate the dissolution profile in comparison with a reference product. The formulation development work was initiated with wet granulation. Telmisartan was converted to its sodium salt by dissolving in aqueous solution of sodium hydroxide to improve solubility and drug release. Lactose monohydrate and microcrystalline cellulose were used as diluents. Starch paste is prepared in purified water and was used as the binder. Sodium starch glycolate is added as a disintegrating agent. Magnesium stearate was used as the lubricant. The prepared granules were compressed into a double-layer compression machine. The tablets thus formulated with higher proportion of sodium starch glycolate showed satisfactory physical parameters, and it was found to be stable and in vitro release studies are showed that formulation (F-T5H5) was 101.11% and 99.89% respectively. The formulation T5H5 is further selected and compared with the release profile of the innovator product, and was found to be similar (f2 factor) to that of the marketed product. The results suggest the feasibility of developing bilayer tablets consisting of telmisartan and hydrochlorothiazide for the convenience of patients with hypertension.  

Human primary retinal cells as an in-vitro model for investigating defective signalling caused by OPTN mutants associated with glaucoma

2021 ◽  
pp. 105075
Author(s):  
Zuberwasim Sayyad ◽  
Sushma Vishwakarma ◽  
Tarjani Vivek Dave ◽  
Milind N. Naik ◽  
Vegesna Radha ◽  
...  
Keyword(s):  
In Vitro Model ◽  
Retinal Cells ◽  
Vitro Model

scholarly journals Photoelectric Dye, NK-5962, as a Potential Drug for Preventing Retinal Neurons from Apoptosis: Pharmacokinetic Studies Based on Review of the Evidence

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 591
Author(s):  
Toshihiko Matsuo ◽  
Shihui Liu ◽  
Tetsuya Uchida ◽  
Satomi Onoue ◽  
Shinsaku Nakagawa ◽  
...  
Keyword(s):  
Biological Evaluation ◽  
Pharmacokinetic Studies ◽  
Retinal Neurons ◽  
Retinal Cells ◽  
Intravitreous Injection ◽  
Rcs Rats ◽  
Photoelectric Dye ◽  
Dark Conditions

NK-5962 is a key component of photoelectric dye-based retinal prosthesis (OUReP). In testing the safety and efficacy, NK-5962 was safe in all tests for the biological evaluation of medical devices (ISO 10993) and effective in preventing retinal cells from death even under dark conditions. The long-term implantation of the photoelectric dye-coupled polyethylene film in the subretinal space of hereditary retinal dystrophic (RCS) rats prevented neurons from apoptosis in the adjacent retinal tissue. The intravitreous injection of NK-5962 in the eyes of RCS rats, indeed, reduced the number of apoptotic cells in the retinal outer nuclear layer irrespective of light or dark conditions. In this study, we reviewed the in vitro and in vivo evidence of neuroprotective effect of NK-5962 and designed pharmacokinetic experiments. The in vitro IC50 of 1.7 μM, based on the protective effect on retinal cells in culture, could explain the in vivo EC50 of 3 μM that is calculated from concentrations of intravitreous injection to prevent retinal neurons from apoptosis. Pharmacokinetics of NK-5962 showed that intravenous administration, but not oral administration, led to the effective concentration in the eye of rats. NK-5962 would be a candidate drug for delaying the deterioration of retinal dystrophy, such as retinitis pigmentosa.

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