On the biochemical basis of HCN production in the millipede Harpaphe haydeniana (Xystodesmidae: Polydesmida)

1978 ◽  
Vol 56 (1) ◽  
pp. 7-16 ◽  
Author(s):  
S. S. Duffey ◽  
G. H. N. Towers
Keyword(s):  
Immediate Release ◽  
Reaction Chamber ◽  
Large Droplet ◽  
Ph Optimum ◽  
Hydroxynitrile Lyase ◽  
Biochemical Basis ◽  
Oxidus Gracilis ◽  
Reaction Chambers

Harpaphe haydeniana was shown to synthesize HCN and benzaldehyde in a manner similar to that of plants. By the injection of appropriate 14C precursors it was possible to isolate small quantities of the radioactive intermediates, phenylacetaldoxime, phenylacetonitrile, a glycoside of mandelonitrile, and mandelonitrile. The millipede stores a large droplet of D-mandelonitrile ((R)-mandelonitrile) in the storage vestibule of each cyanogenic gland.Mandelonitrile dissociates in vivo to HCN and benzaldehyde. The HCN is incorporated into β-cyanoalanine and asparagine. and benzaldehyde is oxidized to P-hydroxybenzoic acid.Two enzymes, β-glucosidase and α-hydroxynitrile lyase, were detected in paranotal extracts of H. haydeniana. The α-hydroxynitrile lyase is restricted to the reaction chamber of the cyanogenic gland and functions to promote the immediate release of HCN. It was also detected in freshly excreted glandular fluid of Oxidus gracilis, Sigmoria nantahalae, Cherokia georgiana, and Cleptoria rileyi. The pH of the fluid in these reaction chambers was found to be about 4, which corresponds to the pH optimum of the lyase.

scholarly journals Development and In Vitro-In Vivo Evaluation of a Novel Sustained-Release Loxoprofen Pellet with Double Coating Layer

Pharmaceutics ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 260 ◽  
Author(s):  
Dongwei Wan ◽  
Min Zhao ◽  
Jingjing Zhang ◽  
Libiao Luan
Keyword(s):  
Citric Acid ◽  
Drug Release ◽  
Sustained Release ◽  
Release Rate ◽  
Diffusion Rate ◽  
Immediate Release ◽  
Pharmacokinetic Studies ◽  
Release Tablet

This study aimed to develop a novel sustained release pellet of loxoprofen sodium (LXP) by coating a dissolution-rate controlling sub-layer containing hydroxypropyl methyl cellulose (HPMC) and citric acid, and a second diffusion-rate controlling layer containing aqueous dispersion of ethyl cellulose (ADEC) on the surface of a LXP conventional pellet, and to compare its performance in vivo with an immediate release tablet (Loxinon®). A three-level, three-factor Box-Behnken design and the response surface model (RSM) were used to investigate and optimize the effects of the citric acid content in the sub-layer, the sub-layer coating level, and the outer ADEC coating level on the in vitro release profiles of LXP sustained release pellets. The pharmacokinetic studies of the optimal sustained release pellets were performed in fasted beagle dogs using an immediate release tablet as a reference. The results illustrated that both the citric acid (CA) and ADEC as the dissolution- and diffusion-rate controlling materials significantly decreased the drug release rate. The optimal formulation showed a pH-independent drug release in media at pH above 4.5 and a slightly slow release in acid medium. The pharmacokinetic studies revealed that a more stable and prolonged plasma drug concentration profile of the optimal pellets was achieved, with a relative bioavaibility of 87.16% compared with the conventional tablets. This article provided a novel concept of two-step control of the release rate of LXP, which showed a sustained release both in vitro and in vivo.

scholarly journals Benznidazole Extended-Release Tablets for Improved Treatment of Chagas Disease: Preclinical Pharmacokinetic Study

2016 ◽  
Vol 60 (4) ◽  
pp. 2492-2498 ◽  
Author(s):  
Marcelo Gomes Davanço ◽  
Michel Leandro Campos ◽  
Talita Atanazio Rosa ◽  
Elias Carvalho Padilha ◽  
Alejandro Henao Alzate ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Extended Release ◽  
Hydroxypropyl Methylcellulose ◽  
Immediate Release ◽  
Relative Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Success ◽  
Preclinical Pharmacokinetics ◽  
Bioavailability Study

ABSTRACTBenznidazole (BNZ) is the first-line drug for the treatment of Chagas disease. The drug is available in the form of immediate-release tablets for 100-mg (adult) and 12.5-mg (pediatric) doses. The drug is administered two or three times daily for 60 days. The high frequency of daily administrations and the long period of treatment are factors that significantly contribute to the abandonment of therapy, affecting therapeutic success. Accordingly, this study aimed to evaluate the preclinical pharmacokinetics of BNZ administered as extended-release tablets (200-mg dose) formulated with different types of polymers (hydroxypropyl methylcellulose K4M and K100M), compared to the tablets currently available. The studies were conducted with rabbits, and BNZ quantification was performed in plasma and urine by ultraperformance liquid chromatography methods previously validated. The bioavailability of BNZ was adequate in the administration of extended-release tablets; however, with the administration of the pediatric tablet, the bioavailability was lower than with other tablets, which showed that the clinical use of this formulation should be monitored. The pharmacokinetic parameters demonstrated that the extended-release tablets prolonged drug release from the pharmaceutical matrix and provided an increase in the maintenance of the drug concentrationin vivo, which would allow the frequency of administration to be reduced. Thus, a relative bioavailability study in humans will be planned for implementation of a new product for the treatment of Chagas disease.

In vitro dissolution method fitted to in vivo absorption profile of rivaroxaban immediate-release tablets applying in silico data

2017 ◽  
Vol 44 (5) ◽  
pp. 723-728 ◽  
Author(s):  
Nathalie R. Wingert ◽  
Natália O. dos Santos ◽  
Sarah C. Campanharo ◽  
Elisa S. Simon ◽  
Nadia M. Volpato ◽  
...  
Keyword(s):  
In Silico ◽  
Immediate Release ◽  
In Vitro Dissolution ◽  
Absorption Profile ◽  
Dissolution Method ◽  
In Vivo Absorption

The Drosophila extramacrochaetae protein antagonizes sequence-specific DNA binding by daughterless/achaete-scute protein complexes

Development ◽  
1991 ◽  
Vol 113 (1) ◽  
pp. 245-255 ◽  
Author(s):  
M. Van Doren ◽  
H.M. Ellis ◽  
J.W. Posakony
Keyword(s):  
Dna Binding ◽  
Cell Fate ◽  
Protein Complexes ◽  
Competitive Inhibitor ◽  
Binding Activity ◽  
Regulatory Function ◽  
Biochemical Basis ◽  
Dna Binding Activity

In Drosophila, a group of regulatory proteins of the helix-loop-helix (HLH) class play an essential role in conferring upon cells in the developing adult epidermis the competence to give rise to sensory organs. Proteins encoded by the daughterless (da) gene and three genes of the achaete-scute complex (AS-C) act positively in the determination of the sensory organ precursor cell fate, while the extramacrochaetae (emc) and hairy (h) gene products act as negative regulators. In the region upstream of the achaete gene of the AS-C, we have identified three ‘E box’ consensus sequences that are bound specifically in vitro by hetero-oligomeric complexes consisting of the da protein and an AS-C protein. We have used this DNA-binding activity to investigate the biochemical basis of the negative regulatory function of emc. Under the conditions of our experiments, the emc protein, but not the h protein, is able to antagonize specifically the in vitro DNA-binding activity of da/AS-C and putative da/da protein complexes. We interpret these results as follows: the heterodimerization capacity of the emc protein (conferred by its HLH domain) allows it to act in vivo as a competitive inhibitor of the formation of functional DNA-binding protein complexes by the da and AS-C proteins, thereby reducing the effective level of their transcriptional regulatory activity within the cell.

scholarly journals Level A IVIVC for immediate release tablets confirms in vivo predictive dissolution testing for ibuprofen

2021 ◽  
pp. 121415
Author(s):  
I Cámara-Martinez ◽  
J.A. Blechar ◽  
A. Ruiz-Picazo ◽  
A. Garcia-Arieta ◽  
C. Calandria ◽  
...  
Keyword(s):  
Immediate Release ◽  
Dissolution Testing

scholarly journals Requirements for Additional Strength Biowaivers for Modified Release Solid Oral Dosage Forms in International Pharmaceutical Regulators Programme Participating Regulators and Organisations: Differences and Commonalities

2021 ◽  
Vol 24 ◽  
pp. 548-562
Author(s):  
Matthias Shona Roost ◽  
Henrike Potthast ◽  
Chantal Walther ◽  
Alfredo García-Arieta ◽  
Ivana Abalos ◽  
...  
Keyword(s):  
Immediate Release ◽  
Dosage Forms ◽  
Oral Dosage ◽  
In Vitro Dissolution ◽  
Quantitative Composition ◽  
Modified Release ◽  
Solid Oral Dosage Forms ◽  
Oral Dosage Forms

This article describes an overview of waivers of in vivo bioequivalence studies for additional strengths in the context of the registration of modified release generic products and is a follow-up to the recent publication for the immediate release solid oral dosage forms. The current paper is based on a survey among the participating members of the Bioequivalence Working Group for Generics (BEWGG) of the International Pharmaceutical Regulators Program (IPRP) regarding this topic. Most jurisdictions consider the extrapolation of bioequivalence results obtained with one (most sensitive) strength of a product series as less straightforward for modified release products than for immediate release products. There is consensus that modified release products should demonstrate bioequivalence not only in the fasted state but also in the fed state, but differences exist regarding the necessity of additional multiple dose studies. Fundamental differences between jurisdictions are revealed regarding requirements on the quantitative composition of different strengths and the differentiation of single and multiple unit dosage forms. Differences in terms of in vitro dissolution requirements are obvious, though these are mostly related to possible additional comparative investigations rather than regarding the need for product-specific methods. As with the requirements for immediate release products, harmonization of the various regulations for modified release products is highly desirable to conduct the appropriate studies from a scientific point of view, thus ensuring therapeutic equivalence.

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