1,720,968 research outputs found
1:2 Inclusion complex progesterone/HPBCD studied by Raman and NMR spectroscopy
No full textComplexes between Progesterone (P) and β-cyclodextrin (BCD) to obtain water soluble formulations are widely known; since hydroxypropyl β-cyclodextrin (HPBCD) displays higher water solubility (48% p/v), we started experiments to achieve a better solubilization of the hormone, to obtain up to 50 mg/ml progesterone concentration in physiological solution, to formulate a suitable dosage form for progesterone therapy.
We developed a production process in which the residual BCD (commercial HPBCD contains up to 0.8 % of unreacted material) is preliminarly separated by the formation of a poorly soluble complex. The stoichiometry and stability constant of the desired soluble complex were calculated by phase/solubility study. DSC and X-Ray analysis confirmed the absence of crystalline P in the final freeze-dried powder. The structural evaluation by spectroscopic analysis (Raman, FTIR and NMR) confirms the presence of an inclusion complex with a stoichiometry guest/host 1:2. The Raman spectrum of P shows tree sharp signals at 1616, 1664 and 1669 cm-1 due to the two carbonyls in position 3 and 20 of the steroid structure. HPBCD alone does not show signals in the considered area. P/HPBCD complex show a broad main signal at 1657 cm-1with a minor signal at 1691 cm-1 This change in the spectrum indicates the inclusion of the progesterone involving both rings A and D of the steroid structure. This idea was also confirmed by FT-IR spectroscopy (right).
NMR experiment shows shifts of signals attributed to P protons 4, 18,19 and 21 indicating again a involvement of rings A and D in the inclusion complex (left)
New injectable formulation containing water soluble Progesterone-Hydroxypropyl-beta-cyclodextrin complex
No full textProgesterone (P) is a natural hormone used as a drug to control reproductive function and for postmenopausal therapy. Oral and vaginal routes display low bioavailability and, in addition, oral route has a limited usefulness, because of P short half-life and extensive degradation after absorption. Therefore the injection route should be the preferred choice, since the oily solution and the aqueous suspension allow only intramuscolar administration. This encourages the research of new injectable pharmaceutical form with increase of the patient compliance. Water-soluble P formulations represent a suitable solution, because they could be administered also by subcutaneous route, therefore allowing auto medication and less pain during the treatment is expected.
Pitha et al. described the use of Cyclodextrins to increase the water solubility of Progesterone (P), through the formation of an inclusion complex to obtain a water soluble formulation (1). Also other authors, using different physico-chemical methods (2, 3, 4), reported experimental evidences of the inclusion complex formation between P and b-cyclodextrin and derivatives. Among the cyclodextrins tested hydroxypropyl-b-cyclodextrin (HPBCD) is a suitable choice for formulations containing therapeutic concentration of P. The therapeutic dosage of P by injection varies from 5 to 200 mg. as a function of the specific pathology (5). HPBCD, displaying high water solubility (48% p/v), allows solubilisation of large quantity of P. Considering the formation of a 1:2 complex, it is possible to obtain solutions up to 50 mg/ml P, which is a considerable dosage in the progesterone therapy. In the development of P/HPBCD complex we observed the formation of a light precipitate under stability ICH conditions. Choi et al (4) and also by Pitha et al (1) noticed the precipitate formation, but its chemical structure was not elucidated.
This work describes a method to obtain a P/HPBCD without insoluble particles, the physico-chemical characterization of the precipitate and of the purified inclusion complex
The interaction of basic fibroblast growth factor (bFGF) with heparan sulfate proteoglycans: biochemical bases and biological implications
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Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Structure and conformation of polyalcohols and polyacids obtained from periodate oxyamylose and oxycellulose
No full textBiochemical bases of the interaction of the human basic fibroblast growth factor with glycosaminoglycans: new insights from trypsin digestion studies
No full textHeparins from bovine mucosa and lung, and chemically modified
heparins were assayed for their capacity to: (i) protect human
recombinant basic fibroblast growth factor (bFGF) from tryptic
cleavage; (ii) prevent 1251-bFGF binding to heparan sulphate
proteoglycans present in the extracellular matrix and on the cell
surface of fetal bovine aortic endothelial GM 7373 cell cultures;
(iii) affect 1251-bFGF binding to high-affinity tyrosine kinase
FGF receptors present on the cell membrane of GM 7373 cells;
(iv) inhibit the mitogenic activity exerted by bFGF in the same
cells. The results demonstrate thatthe potency shown by mucosal
heparins in the different assays is a direct function of size, verylow-
molecular-mass heparin (2.0 kDa) being significantly less
effective on a molar basis than unfractionated heparin (13.6 kDa).
Increased flexibility of the backbone structure, as observed in
reduced/oxidized heparins of different size, does not affect the
capacity of the polysaccharide to interact with bFGF. In contrast,
selective 2-O-desulphation, but not 6-O-desulphation, drastically
reduced the capacity of heparin to protect bFGF from proteolytic
cleavage, to affect its interaction with low- and high-affinity sites,
and to inhibit its mitogenic activity. Two preparations of bovine
lung heparin, differing in molecular mass, were as effective as
mucosal heparin in the bFGF-tryptic-digestion assay and the
endothelial-cell proteoglycan-binding assay, but they were highly
inefficient at inhibiting the capacity of bFGF to interact with its
tyrosine kinase receptors. Bovine lung heparins were also less
effective than mucosal heparin as bFGF antagonists in GM
7373-cell-proliferation assays. N-Desulphated/N-acetylated
bovine lung heparin retained only a significant capacity to
protect bFGF from tryptic cleavage. The results demonstrate
that different chemical features of the heparin molecule, including
decrease in molecular mass, selective desulphation, disaccharide
composition and clustering, affect differently the capacity of the
glycosaminoglycan to interact with bFGF and to influence its
biological behaviour in different assays in vitro and in endothelial
cell cultures. Our findings should aid the design of synthetic
oligosaccharides aimed at improving the. bioavailability of bFGF
when administered in vivo as a therapeutic agent
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Distinct role of 2-O, N-, and 6-O-sulfate groups of heparin in the formation of the ternary complex with basic fibroblast growth factor and soluble FGF receptor-1
No full textInteraction of basic fibroblast growth factor (bFGF) with heparan sulfate proteoglycans (HSPGs) plays an important role in the binding of bFGF to its tyrosine kinase receptor (FGFR). The molecular bases of this interaction were investigated by evaluating the capacity of conventional and selectively desulfated heparins i) to affect the binding of bFGF to FGFR and HSPGs of NIH 3T3 cells transfected with FGFR-1/flg cDNA, ii) to facilitate the interaction of bFGF with a recombinant soluble form of the extracellular domain of FGFR-1/flg (xcFGFR-1), and iii) to protect xcFGFR-1 from tryptic cleavage. 6-O-desulfated (6-O-DS) heparin, but not 2-O-desulfated (2-O-DS) and N-desulfated/N-acetylated (N-DS/N-Ac) heparins, retains the capacity to bind bFGF, as assessed by its ability to inhibit bFGF-binding to cell-associated FGFR-1 and HSPGs. On the other hand, at variance with conventional heparin, 2-O-DS, N-DS/N-Ac, and 6-O-DS heparins are all ineffective in potentiating the binding of bFGF to xcFGFR-1 and protecting xcFGFR-1 from tryptic cleavage. The data indicate that 6-O-sulfate groups are not essential for the interaction of heparin with bFGF but are involved in the interaction with xcFGFR-1. Our findings support the hypothesis that HSPGs modulate the binding of bFGF to FGFR through the formation of a ternary complex in which the glycosaminoglycan chains interact with bFGF via 2-O- and N-sulfate groups and with FGFR also via 6-O-sulfate groups
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