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Biomedical subjects

A Fini

Publications and source records attributed to A Fini.

18 recordsLinked to original sources
PubMed1992

Effect of basic cholane derivatives on intestinal cholic acid metabolism: in vitro and in vivo activity.

A representative series of hydroxy-5 beta-cholanyl-24-amines were tested both in vitro and in vivo with respect to their activity against the intestinal bacteria responsible for bile acid metabolism. For the in vitro studies, radiolabeled [14C]cholic acid was incubated with human stools both in aerobic and anaerobic conditions in the presence of the title compounds at a dose of 10 micrograms/mL, and the biotransformation of cholic acid into radiolabeled deoxycholic acid and other metabolites was followed by TLC-radiochromatography. Of the compounds studied, 3 alpha, 12 alpha-dihydroxy-5 beta-cholan-24-N-methylamine showed the highest activity. This compound was used for the in vivo studies and was shown to inhibit the formation of endogenous secondary bile acids when chronically administered to rats at a dose of 60 micrograms/day for 15 days. The treated rats showed an increased ratio of taurocholic acid (primary bile acid) to taurodeoxycholic acid (secondary bile acid) in bile, a fact further suggesting a potent antibacterial activity of the compound toward bacteria responsible for bile acid metabolism.

Aerobiosis↗
PubMed1992

Basic cholane derivatives. XI: Comparison between acid and basic derivatives.

A series of hydroxycholan-24-amines was synthesized; the carboxyl group of starting unconjugated bile acids was transformed into a basic moiety [-NH2, -NHCH3, -N(CH3)2, or -NHCH2C6H5] at C-24. Solubilities, acidities, partition coefficients, and critical micellar concentrations were measured and compared with those of the corresponding bile acids. Because the steroid nucleus in the amines is the same as that in the bile acids, most of the physical-chemical properties of the two compound classes were similar. The amines were more soluble than the corresponding acids; solubilities depended mainly on the number of steroid hydroxyls and, to a lesser extent, on the side chain. Amines are strong bases in water, whereas unconjugated bile acids can be classified as weak acids. N-Benzylamino derivatives have higher log P (P is partition coefficient) values, as a consequence of the bulky hydrophobic substituent; the log P values were almost the same for the amines and the bile acids and depended on the steroid hydroxyls. Amines can self-aggregate at an acidic pH and form cationic micelles; the critical micellar concentrations of amines were of the same order of magnitude as those of bile acids. The introduction of a basic function in the side chain of the cholane moiety increased the antimicrobial activity toward most gram-positive strains.

Bile Acids and Salts↗
PubMed1992

Chemical properties of bile acids. V. Interaction with concentrated sulfuric acid.

The reaction between concentrated sulfuric acid and steroid hydroxy compounds, previously studied for a series of sterols, was used to develop an analytical method for bile acids. The reaction generates species absorbing in the wavelength ranges 300-320 and 370-390 nm, corresponding to isomeric allylic and dienylic carbocations. Eleven bile acids were examined and influence of time, temperature and sulfuric acid concentration on the chromogenic reaction was studied. The linear dependence of absorbance on concentration of individual bile acids demonstrates that the method can be used to measure spectrophotometrically micromolar concentrations of bile acids.

Adsorption↗
PubMed1991

Release of ketoprofen from dermal bases in presence of cyclodextrins: effect of the affinity constant determined in semisolid vehicles.

We describe a method to determine the affinity constant values between Ketoprofen and beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin in semisolid vehicles. The method is based on the diffusion of the drug, released from semisolid vehicles, through a lipidic non porous membrane. The affinity constants of Ketoprofen towards cyclodextrins as determined in semisolid media better represent the release of the drug from dermal bases than the corresponding values in aqueous systems.

Chemical Phenomena↗
PubMed1991

Antimicrobial activity of basic cholane derivatives. X. Synthesis of 3 alpha- and 3 beta-amino-5 beta-cholan-24-oic acids.

A simple and convenient route to 3 alpha- and 3 beta-amino-5 beta-cholan-24-oic acids was developed via Leuckart-Wallach amination reduction and subsequent acid hydrolysis. Two epimeric formylamino derivatives were produced (alpha and beta), approximately in a 1:1 ratio, as determined by 13C nuclear magnetic resonance spectroscopy. The two isomers were separated by making use of their different solubilities in ethyl ether. The absolute configuration of the two amino acids was assigned by comparison with authentic reference samples.

Lithocholic Acid↗
PubMed1991

Chemical properties-dissolution relationship. IV. Behaviour in solution of the diclofenac/N-(2-hydroxyethyl) pyrrolidine salt (DHEP).

The behaviour in solution of the salt formed between diclofenac and N-(2-hydroxyethyl) pyrrolidine (DHEP) was examined. This salt is more soluble and dissolves more rapidly than sodium diclofenac and tends to give rise to supersaturated solutions, that only slowly evolve to equilibrium. Above 35 mM of DHEP, the solutions show unexpected solubilization ability towards sparingly soluble materials. The faster plasma level found, when DHEP is administered per os, can be associated to this weak detergency. These properties make DHEP a suitable pharmaceutical form to prepare extemporary solutions for short term analgesic therapy.

Diclofenac↗
PubMed1991

Diffusion of naproxen in presence of beta-cyclodextrin across a silicone rubber membrane.

The diffusion of Naproxen through a silicone rubber membrane has been studied for four different release systems: solution and suspension both of Naproxen and Naproxen beta-cyclodextrin coprecipitates. Differences in transport between the two forms indicate the existence of an interaction between the acid and beta-cyclodextrin in solution. Independence of the transport on pH in the case of the coprecipitate indicates rapid liberation of Naproxen from the complex prior to entering the membrane. Increase in the cumulative amount diffused for the suspension of Naproxen with increasing pH was interpreted as due to an increase in its solubility with increasing pH.

Cyclodextrins↗
PubMed1991

Controlled release of hydrocortisone acetate from dermal bases.

The effect of the complexation with beta-cyclodextrin, hydroxypropyl beta-cyclodextrin and polyvinylpyrrolidone on the diffusion kinetics of hydrocortisone acetate through a non porous lipidic membrane was analyzed starting from different dermal bases: a Carbopol gel and lanovaseline. A constant diffusive gradient was achieved; this suggests that the complexation equilibrium controls the diffusable form, according to its stability constant. The following sequence was observed for the cumulative amount diffused: hydrocortisone acetate greater than hydrocortisone acetate/polyvinylpyrrolidone greater than hydrocortisone acetate/hydroxypropyl beta-cyclodextrin greater than hydrocortisone acetate/beta-cyclodextrin. Such behaviour was analyzed in terms of the main physical chemical parameters of the systems examined.

Acrylic Resins↗
PubMed1990

Antimicrobial activity of basic cholane derivatives. Part IX.

Twenty new compounds derived from deoxycholic acid have been synthesized. They contain two basic functions: at C-24 (benzylamino, morpholino, diethanolamino, N,N-diethylethylenediamino, N-methylpiperazino) and at beta-C-3 (amino, methylamino, ethylamino, benzylamino). The compounds showed interesting antimicrobial activity, as expressed in terms of the low M.I.C. values (0.9-31-micrograms/ml) against five Gram(+) and four Gram(-) strains, two fungi and one yeast. The compounds inhibit the production of a fluorescent pigment in Pseudomonas aeruginosa: this result suggests that the ability to cross the bacterium cell membrane is the first step of activity. A discussion in terms of structure-activity relationship is reported.

Anti-Bacterial Agents↗
PubMed1990

Quantitative structure-antimicrobial activity relationship in 5 beta-cholanyl-24-benzylamine derivatives.

Some representative physicochemical properties of benzylamido and amino derivatives of common bile acids have been determined and correlated with their antimicrobial activity against gram-positive bacterial strains. Steroid hydroxyls do not affect the basicity of amino derivatives; they promote solubility in a parallel way to unconjugated bile acids and mainly control hydrophobicity of this class of compounds as measured by log P values. Activity was correlated to hydrophobicity; that is, the nature of the side chain modulated activity, affected basicity, and facilitated changes in partition ability. Benzylamino derivatives proved to be even more active than the corresponding amides when ionization is taken into account. Trihydroxy derivatives possess the lowest log P values and were practically inactive. Decreased activity was also observed in those cases where, due to the orientation of the hydroxy group in the 6 or 7 position, the back beta face of the molecule had a reduced hydrophobic surface area. Antimicrobial activity, in terms of -log MIC (minimal inhibitory concentration), was found to correlate linearly with log P values of uncharged species. This linear relationship is discussed with respect to the structure of the steroid moiety and the ability of these molecules to cross cellular membranes.

Anti-Bacterial Agents↗
PubMed1990

Bile acid structure-activity relationship: evaluation of bile acid lipophilicity using 1-octanol/water partition coefficient and reverse phase HPLC.

Two independent methods have been developed and compared to determine the lipophilicity of a representative series of naturally occurring bile acids (BA) in relation to their structure. The BA included cholic acid (CA), chenodeoxycholic acid (CDCA), ursodeoxycholic acid (UDCA), deoxycholic acid (DCA), hyodeoxycholic acid (HDCA), ursocholic acid (UCA), hyocholic acid (HCA), as well as their glycine and taurine amidates. Lipophilicity was determined using a 1-octanol/water shake-flask procedure and the experiments were performed at different pH and ionic strengths and at initial BA concentrations below their critical micellar concentrations (CMC) and the water solubility of the protonated form. The experimental data show that both the protonated (HA) and ionized (A-) forms of BA can distribute in 1-octanol, and consequently a partition coefficient for HA (logP' HA) and for A- (logP' A-) must be defined. An equation to predict a weighted apparent distribution coefficient (D) value as a function of pH and pKa has been developed and fits well with the experimental data. Differences between logP for protonated and ionized species for unconjugated BA were in the order of 1 log unit, which increased to 2 for glycine-amidate BA. The partition coefficient of the A- form increased with Na+ concentration and total ionic strength, suggesting an ion-pair mechanism for its partition into 1-octanol. Lipophilicity was also assessed using reverse phase chromatography (C-18-HPLC), and a capacity factor (K') for ionized species was determined. Despite a broad correlation with the logP data, some BA behaved differently. The logP values showed that the order of lipophilicity was DCA greater than CDCA greater than UDCA greater than HDCA greater than HCA greater than CA greater than UCA for both the protonated and ionized unconjugated and glycine-amidate BA, while the K' data showed an inversion for some BA, i.e., DCA greater than CDCA greater than CA greater than HCA greater than UDCA greater than HDCA greater than UCA. The logP data fitted well with other indirect measurements of BA monomeric lipophilicity such as albumin binding or accessible total hydrophobic surface area data calculated by energy minimization and molecular computer graphics. Differences between unconjugated and amidated BA are consistent with the presence of an amide bond and a lower pKa when pH dependence was studied. Capacity factors, on the other hand, were related to properties of BA micelles such as cholesterol-solubilizing capacity and membrane disruption, reflecting the BA detergency.(ABSTRACT TRUNCATED AT 400 WORDS)

Bile Acids and Salts↗
PubMed1989

Availability of NSAIDH beta-cyclodextrin inclusion complexes.

The diffusion of a series of non steroidal antiinflammatory drugs through a silicone rubber membrane has been studied from suspensions both of the free and beta-cyclodextrin complexes forms at different pH values of the medium. Higher diffusion rates of the complexed forms as compared with the free ones and a rate-limiting effect of the apparent stability constant in the diffusion of the complexes were observed.

Administration, Topical↗
PubMed1989

Antimicrobial activity of basic cholane derivatives, VIII.

Two series of new compounds derived from deoxycholic acid have been synthesized: 3,12-dioxo-5 beta-cholan-24-N-substituted amides and their 3 beta-amino and 3 beta-N-alkylamino derivatives. The first series of five compounds 1-5 carries at C-24 the residue of benzylamine, morpholine, diethanolamine, N,N-diethyl-ethylenediamine, and N-methylpiperazine. The second series of twenty compounds 1A-D - 5A-D was prepared by means of reductive amination starting from the compounds of the first series. This reaction proved to be regioselective and stereospecific: it attacks only C-3 of the steroid moiety and introduces the following axial beta-oriented substituents: amino, methylamino, ethylamino, and benzylamino. The compounds of the first series showed moderate scattered antimicrobial activity; while introduction of the 3 beta-amino and 3 beta-N-alkylamino residue greatly increased activity towards Gram (+) strains; even yeast and fungi appear to be sensitive towards this last series of compounds. The results have been discussed with respect to the nature of the substituents both at C-3 and C-24, the highest activity being associated to the hydrophobicity of these residues.

Anti-Bacterial Agents↗
PubMed1989

Diffusion of ketoprofen from coprecipitates through a non porous lipidic membrane.

The effect of inclusion with beta-cyclodextrin or hydroxypropyl beta-cyclodextrin on the diffusion kinetics of Ketoprofen through a non porous lipidic membrane was analyzed starting from different dermal bases: a Carbopol gel, o/w emulsion and a fatty ointment. A constant diffusive gradient was achieved with the included forms at each concentration of the active principle in the vehicle. This suggests that the complex controls the diffusable form, according to its stability constant. The following sequence was observed for the diffusion rate: Carbopol gel greater than o/w emulsion greater than fatty ointment appears to depend mainly on the membrane/vehicle partition coefficient.

Chemical Phenomena↗
PubMed1978

Retained gastric antrum syndrome diagnosed by [99mTc] pertechnetate scintiphotography in man: hormonal and radioisotopic study of two cases.

Retained-antrum syndrome is a rare condition, occurring in Billroth II gastrectomised patients, in which an ulcer recurs associated with high levels of circulating gastrin. Some gastrin tests are useful to differentiate a retained antrum from a gastrinoma, but a firm diagnosis is sometimes very difficult. We have studied two cases of retained-antrum syndrome both by gastrin tests and by [99mTc] pertechnetate scintiphotography. By this method a prominent area of activity was observed on the anatomic site of the duodenal stump bottom. It appeared after 20 or 30 min and lasted for the 2 hr of observation. After surgical resection, no area of activity was observed at the scintiphotographic followup. No false positive was observed out of the more than 30 subjects studied. Scintiphotography by pertechnetate seems able to demonstrate the presence and the size of retained gastric antrum in B II gastrectomised patients with recurrent ulcer.

Diagnosis, Differential↗
PubMedDate not supplied

Serum thymidine kinase (TK) evaluation in HIV infection.

Serum thymidine kinase (TK), measured using Prolifigen TK-REA, from AB Sangtec Medical, was investigated in 24 HIV seropositive patients without immunological alterations, 26 seropositives with immunological alterations, 125 LAS, 25 ARC, and 20 AIDS. Subjects with serological markers of prior EBV, HBV, and CMV infection were included but none with acute infectious mononucleosis or acute viral hepatitis. Serum TK was elevated from the beginning of the HIV infection, the seropositive stage, and more markedly afterwards during the course of the infection, with a close correlation with the stage. TK also increased during AZT treatment, due to bone-marrow toxicity. On lowering the dosage or discontinuing the drug TK returned to basal levels. Although the rise in serum may well not be correlated only with the HIV infection, it does add to the picture given by other clinical and/or laboratory methods. Serum TK can be a helpful laboratory test in the follow-up of patients with HIV infection, especially when serum levels are disproportionate to the stage, opportunistic infections, lymphoproliferative malignancies. In such cases bone-marrow toxicity due to treatment can be suspected.

Acquired Immunodeficiency Syndrome↗