In Vitro Kinetic Studies of the Reaction of Hydralazine and its Acetone Hydrazone with Pyruvic Acid

1988 ◽  
Vol 77 (3) ◽  
pp. 280-283 ◽  
Author(s):  
Masahiro Iwaki ◽  
Taro Ogiso ◽  
Yoshimasa Ito
Keyword(s):  
Pyruvic Acid ◽  
Kinetic Studies

Insulin secretion in the spiny mouse (Acomys cahirinus). Dose and time kinetic studies with glucose in vivo and in vitro

Diabetes ◽  
1975 ◽  
Vol 24 (12) ◽  
pp. 1094-1100 ◽  
Author(s):  
A. Rabinovitch ◽  
A. Gutzeit ◽  
A. E. Renold ◽  
E. Cerasi
Keyword(s):  
Insulin Secretion ◽  
Kinetic Studies ◽  
Spiny Mouse ◽  
Acomys Cahirinus

Gastroretentive System of Fluvastatin Sodium by Using Natural Mucilage and Synthetic Polymer

2014 ◽  
Vol 4 (2) ◽  
Author(s):  
Umamaheswara G. ◽  
Anudeep D.
Keyword(s):  
Half Life ◽  
Release Kinetics ◽  
Kinetic Studies ◽  
Diffusion Path ◽  
Synthetic Polymer ◽  
In Vitro Dissolution ◽  
Direct Compression ◽  
Drug Content ◽  
Biological Half Life

Fluvastatin sodium is a novel compound used as cholesterol lowering agent which acts through the inhibition of 3- hydroxyl-3- methyl glutaryl- coenzyme A (HMG-Co A) reductase. It has short biological half life (1-3h) in humans required a dosing frequency of 20 to 40mg twice a day. Due to its short variable biological half life it has been developed to a sustained gastroretentive system with a natural and synthetic polymer and to study how far the natural mucilage improves the sustained activity. Floating tablets were prepared by direct compression method using in combination of natural mucilage and synthetic polymer. Prior to the preparation of tablets the physical mixtures were subjected to FT IR studies and pre compression parameters. After preparation of tablets they were subjected to various tests like swollen index, drug content, In vitro dissolution and release kinetics with pcp disso software etc. The tablets prepared by direct compression shown good in thickness, hardness and uniformity in drug content, the prepared tablets floated more than 12h except FS1 and FS2 shows 9 and 11h. Swollen index studies shows with increase in concentration of polymer the swelling increases the diffusion path length by which the drug molecule may have to travel and cause lag time. In vitro results shows that on increasing the amount of hibiscus polymer the sustain activity is increased because of its integrity and forms a thick swollen mass and reduces the erosion property of the HypromelloseK100M, kinetic studies shows that FS 1, FS2, FS3 followed the Korsmeyer peppas model and the rest FS 4, FS 5, FS6 follows the zero order respectively. Based on n value indicating that the drug release followed super case II transport mechanism due to the erosion of the polymer.

Formulation and Evaluation of Atenolol and Indapamide SR Matrix Tablets for Treatment of Hypertension

2014 ◽  
Vol 7 (2) ◽  
pp. 2450-2458
Author(s):  
Sarika Pundir ◽  
Ashutosh Badola
Keyword(s):  
Kinetic Studies ◽  
Film Coating ◽  
Matrix Tablets ◽  
Wet Granulation ◽  
Simultaneous Estimation ◽  
Matrix Tablet ◽  
Release Agent ◽  
Disintegration Time ◽  
Weight Variation

In the present study we have formulated (F1 to F6) matrix tablets of atenolol and indapamide for the management of hypertension. As in simultaneous estimation of these drugs it was found that a confined release can be formulated. In the formulation of SR matrix tablet by using different concentration of delayed release agent DCP and pregelatinized starch as disintegrant we prepared tablets by wet granulation method. For sustained release action HPMC polymers were used for film coating. Preformulation studies were performed prior to compression. The compressed SR matrix tablets were evaluated for weight variation, hardness, friability, drug content, disintegration time and in vitro drug release using USP dissolution apparatus type 2 (paddle). It was found that the optimized formulation showed 49.33%, 48.90%, 48.52%, 47.65%, 46.84% and 46.51% release for atenolol in 12 hours respectively. However, indapamide released 49.62%, 49.39%, 48.72%, 48.27%, 47.59% and 47.36% at the end of 12 hr. The IR spectrum study revealed that there is no disturbance in the principal peaks of pure drugs atenolol and indapamide. This confirms the integrity of pure drugs and no incompatibility of them with excipients. The stability studies were carried out for the optimized batch for one months and it showed satisfactory results. The kinetic studies of the formulations revealed that diffusion is the predominant mechanism of drug and release follows Zero-order, Super case II transport.

Peroxidases from Tulip Bulbs (Tulipa fosteriana, L.) Oxidize Xenobiotics NNitrosodimethylamine and N-Nitroso-N-methylaniline in vitro

1997 ◽  
Vol 62 (11) ◽  
pp. 1804-1814 ◽  
Author(s):  
Marie Stiborová ◽  
Hana Hansíková
Keyword(s):  
Cytochromes P450 ◽  
Kinetic Studies ◽  
The Other ◽  
Maximal Velocity ◽  
Michaelis Constant ◽  
Other Hand ◽  
Plant Peroxidases ◽  
Tulip Bulbs

Tulip bulbs (Tulipa fosteriana, L.) contain peroxidases catalyzing the oxidation of the xenobiotics N-nitrosodimethylamine (NDMA) and N-nitroso-N-methylaniline (NMA). Three anionic (A1, A2, A3) and four cationic (B, C, D, E) peroxidases were purified from this tissue, partially characterized and used for kinetic studies. Demethylation of NDMA and NMA producing formaldehyde is catalyzed by one anionic (A1) and three cationic (C, D, E) peroxidases. The oxidation of NDMA by tulip peroxidases exhibits the Michaelis-Menten kinetics. The apparent Michaelis constant and the maximal velocity values for this substrate were determined. On the other hand, non-Michaelian kinetics for the NMA oxidation were observed with tulip peroxidases. The most abundant cationic peroxidase (peroxidase C) was used for detailed enzymatic studies. In addition to formation of formaldehyde, methylaniline, aniline, 4-aminophenol and phenol were found to be metabolites formed from NMA. Phenol was formed presumably by N-demethylation via a benzenediazonium ion, while methylaniline, aniline and 4-aminophenol were products of denitrosation of the substrate. The efficiencies of plant peroxidases to oxidize NDMA and NMA in vitro are compared with those of cytochromes P450 and discussed.

scholarly journals Episomal Expression of Specific Sense and Antisense mRNAs in Leishmania amazonensis: Modulation of gp63 Level in Promastigotes and Their Infection of Macrophages In Vitro

2000 ◽  
Vol 68 (1) ◽  
pp. 80-86 ◽  
Author(s):  
De-Qiao Chen ◽  
Bala Krishna Kolli ◽  
Nagendra Yadava ◽  
Hong Gang Lu ◽  
Alice Gilman-Sachs ◽  
...  
Keyword(s):  
Kinetic Studies ◽  
Single Copy ◽  
Antisense Transcription ◽  
Leishmania Amazonensis ◽  
Surface Glycoprotein ◽  
Major Surface Glycoprotein ◽  
Wild Type Clone ◽  
Major Surface ◽  
Specific Sense

ABSTRACT The major surface glycoprotein (gp63) of Leishmania amazonensis is a metalloprotease implicated in the infection of mammalian macrophages. The expression of gp63 and its participation in this infection were further examined by modulating the level of this molecule in a virulent gp63-abundant wild-type clone. Promastigotes were transfected with gp63 genes cloned into aLeishmania-specific vector in two different orientations, leading to the expression of gp63 sense and antisense RNAs. With increasing selective pressure, cell surface gp63 was increasingly augmented in the transfectants with sense transcripts and suppressed to a very low level in those with antisense transcripts. Thus, the expression of gp63 from chromosomal, repetitive genes is not stringently regulated at the protein level and can be substantially reduced by episomal antisense transcription of a single copy. The transfectants differed significantly only in the level of gp63, thereby allowing specific evaluation of this molecule in leishmanial infection of macrophages in vitro. Kinetic studies of infection in vitro indicate that gp63 plays a role not only in the binding of this parasite to these macrophages but also in its intramacrophage survival and replication.

scholarly journals Release Kinetic Studies of Stevia rebaudiana Extract Capsules from Sodium Alginate and Inulin by Ionotropic Gelation

2018 ◽  
Vol 2018 ◽  
pp. 1-8
Author(s):  
Juan Pablo Quintal Martínez ◽  
Jorge Carlos Ruiz Ruiz ◽  
Maira Rubí Segura Campos
Keyword(s):  
Sodium Alginate ◽  
Release Kinetics ◽  
Stevia Rebaudiana ◽  
Kinetic Studies ◽  
Release Kinetic ◽  
Steviol Glycosides ◽  
Ionotropic Gelation ◽  
Diffusion Controlled ◽  
Release Analysis

This study was oriented towards encapsulation of S. rebaudiana extract and the study of its release kinetics. The desired encapsulation was achieved by the ionotropic gelation method using sodium alginate and inulin of polymeric constituents. Characterization of the capsules was performed by micrometric properties, encapsulation efficiency, in vitro extract release analysis, and biological activity of released extract. The in vitro release profiles from different capsules were applied on different kinetic models. The prepared capsules were found spherical in shape with diameters ranging from 2.07 to 2.63 mm, having the encapsulation efficiencies of 43.77% and 56.53% for phenolic compounds and steviol glycosides, respectively. The best-fit model with the highest correlation coefficient was observed in the Ritger–Peppas model, indicating diffusion controlled principle. The release exponent n value obtained from the Korsmeyer–Peppas model varied between 0.2273 and 1.1719, confirming that the mechanism of S. rebaudiana extract bioactive compounds release was diffusion controlled.

scholarly journals Epigenetic control via allosteric regulation of mammalian protein arginine methyltransferases

2017 ◽  
Vol 114 (38) ◽  
pp. 10101-10106 ◽  
Author(s):  
Kanishk Jain ◽  
Cyrus Y. Jin ◽  
Steven G. Clarke
Keyword(s):  
Cancer Metastasis ◽  
Gene Activation ◽  
Kinetic Studies ◽  
Arginine Methylation ◽  
Histone H4 ◽  
Protein Arginine Methyltransferases ◽  
Wide Range ◽  
Substrate Concentrations

Arginine methylation on histones is a central player in epigenetics and in gene activation and repression. Protein arginine methyltransferase (PRMT) activity has been implicated in stem cell pluripotency, cancer metastasis, and tumorigenesis. The expression of one of the nine mammalian PRMTs, PRMT5, affects the levels of symmetric dimethylarginine (SDMA) at Arg-3 on histone H4, leading to the repression of genes which are related to disease progression in lymphoma and leukemia. Another PRMT, PRMT7, also affects SDMA levels at the same site despite its unique monomethylating activity and the lack of any evidence for PRMT7-catalyzed histone H4 Arg-3 methylation. We present evidence that PRMT7-mediated monomethylation of histone H4 Arg-17 regulates PRMT5 activity at Arg-3 in the same protein. We analyzed the kinetics of PRMT5 over a wide range of substrate concentrations. Significantly, we discovered that PRMT5 displays positive cooperativity in vitro, suggesting that this enzyme may be allosterically regulated in vivo as well. Most interestingly, monomethylation at Arg-17 in histone H4 not only raised the general activity of PRMT5 with this substrate, but also ameliorated the low activity of PRMT5 at low substrate concentrations. These kinetic studies suggest a biochemical explanation for the interplay between PRMT5- and PRMT7-mediated methylation of the same substrate at different residues and also suggest a general model for regulation of PRMTs. Elucidating the exact relationship between these two enzymes when they methylate two distinct sites of the same substrate may aid in developing therapeutics aimed at reducing PRMT5/7 activity in cancer and other diseases.

Liposome encapsulation attenuates hemoglobin-induced vasoconstriction in rabbit arterial segments

1997 ◽  
Vol 82 (6) ◽  
pp. 1826-1835 ◽  
Author(s):  
Alan S. Rudolph ◽  
Anthony Sulpizio ◽  
Paul Hieble ◽  
Victor Macdonald ◽  
Mark Chavez ◽  
...  
Keyword(s):  
Kinetic Studies ◽  
Significant Inhibition ◽  
No Donor ◽  
Liposome Encapsulation ◽  
Vasoconstrictor Response ◽  
Ear Artery ◽  
Rabbit Ear ◽  
Before And After ◽  
Potent Vasoconstrictor

Rudolph, Alan S., Anthony Sulpizio, Paul Hieble, Victor Macdonald, Mark Chavez, and Giora Feuerstein. Liposome encapsulation attenuates hemoglobin-induced vasoconstriction in rabbit arterial segments. J. Appl. Physiol.82(6): 1826–1835, 1997.—Free hemoglobin (Hb) induces a potent vasoconstrictor response that may limit its therapeutic application as a red blood cell replacement. We have investigated whether encapsulation of stroma-free Hb (SFHb) or cross-linked Hb (αα-Hb) in liposomes modulates Hb vasoactivity in isolated blood vessels. Relaxation of rabbit thoracic vessels was measured before and after exposure to acellular SFHb, αα-Hb, and liposome-encapsulated SFHb or αα-Hb. SFHb and αα-Hb caused significant inhibition of carbachol-induced relaxation at 0.5 mg/dl, whereas encapsulation inhibited vessel relaxation at 30- to 60-fold higher Hb concentrations. The contractile response of rabbit ear arterial segments to electrical stimulation in the presence of acellular αα-Hb resulted in a 150% increase (EC150) in contractile amplitude at 0.23 mg/dl, whereas the EC150 for encapsulated αα-Hb was 13.7 mg/dl. Mechanistic studies of the vasoconstrictor activity of Hb demonstrated that acellular αα-Hb had no effect on norepinephrine release in the rabbit ear artery. In addition, neither acellular nor encapsulated αα-Hb preparations inhibited endothelial nitric oxide (NO) synthase activity isolated from bovine pulmonary artery. However, inhibition of vessel relaxation by acellular or encapsulated αα-Hb was reversed by the NO donor S-nitrosylpenacillamine, implicating Hb-NO binding as a possible mechanism for the vasoconstrictor response. In vitro stopped-flow kinetic studies of Hb-NO binding showed similar rates of reaction for conversion of oxyhemoglobin to methemoglobin (metHb; <2 ms), followed by rapid conversion of metHb to NO-Hb (300 ms) for both acellular and encapsulated αα-Hb, demonstrating that liposome encapsulation does not retard NO-Hb binding. The attenuated vasoactivity of encapsulated Hb may, therefore, result from the limited access of encapsulated Hb to NO imposed by the physical size of the liposome and reduced penetration of Hb across the vascular endothelium.

scholarly journals The Rhodococcus opacus PD630 Heparin-Binding Hemagglutinin Homolog TadA Mediates Lipid Body Formation

2010 ◽  
Vol 76 (21) ◽  
pp. 7217-7225 ◽  
Author(s):  
Daniel P. MacEachran ◽  
M. E. Prophete ◽  
A. J. Sinskey
Keyword(s):  
Kinetic Studies ◽  
Lipid Body ◽  
Dry Weight ◽  
Rhodococcus Opacus ◽  
Lipid Bodies ◽  
Heparin Binding ◽  
Tag Biosynthesis ◽  
Tag Accumulation

ABSTRACT Generally, prokaryotes store carbon as polyhydroxyalkanoate, starch, or glycogen. The Gram-positive actinomycete Rhodococcus opacus strain PD630 is noteworthy in that it stores carbon in the form of triacylglycerol (TAG). Several studies have demonstrated that R. opacus PD630 can accumulate up to 76% of its cell dry weight as TAG when grown under nitrogen-limiting conditions. While this process is well studied, the underlying molecular and biochemical mechanisms leading to TAG biosynthesis and subsequent storage are poorly understood. We designed a high-throughput genetic screening to identify genes and their products required for TAG biosynthesis and storage in R. opacus PD630. We identified a gene predicted to encode a putative heparin-binding hemagglutinin homolog, which we have termed tadA (triacylglycerol accumulation deficient), as being important for TAG accumulation. Kinetic studies of TAG accumulation in both the wild-type (WT) and mutant strains demonstrated that the tadA mutant accumulates 30 to 40% less TAG than the parental strain (WT). We observed that lipid bodies formed by the mutant strain were of a different size and shape than those of the WT. Characterization of TadA demonstrated that the protein is capable of binding heparin and of agglutinating purified lipid bodies. Finally, we observed that the TadA protein localizes to lipid bodies in R. opacus PD630 both in vivo and in vitro. Based on these data, we hypothesize that the TadA protein acts to aggregate small lipid bodies, found in cells during early stages of lipid storage, into larger lipid bodies and thus plays a key role in lipid body maturation in R. opacus PD630.

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