Manoalide.

Manoalide is a potent analgesic and antiinflammatory sesterterpene isolated in 1980 from a marine sponge. The antiinflammatory activity of manoalide is due to inhibition of PLA2, through irreversible binding to several lysine residues. The binding is realized by means of the two masked aldehyde functions present in the polar part of manoalide. Of the two aldehyde groups, only that present in the g-hydroxybutenolide ring seems to be essential, since cacospongionolides, naturally occurring analogues lacking the second masked aldehyde group, were also shown to be irreversible PLA2 inhibitors. It appears that the minimum structural requirement for exhibiting manoalide-like PLA2 inhibition would be the presence in the inhibitor of functional groups able to seize the amino groups of PLA2 lysine residues with formation of stable covalent bonds. Many manoalide analogues have been isolated from marine sponges, most of them sharing PLA2 inhibitory properties. Other interesting bioactivities have also been reported for some of these compounds.

Synthesis and comparison of the antiinflammatory activity of manoalide and cacospongionolide B analogues.

We have synthesized analogues of two naturally occurring antiinflammatory marine compounds, manoalide and cacospongionolide B, containing a pyranofuranone moiety which is considered the pharmacophoric group. The two compounds, and hence their analogues, differ in the presence or absence in the dihydropyran ring of an hemiacetal function which was considered essential to irreversibly inactivate phospholipase A2 (PLA2). The two series of compounds were tested for their inhibitory effects on secretory PLA2 belonging to the groups I, II, and III, and the activities were found to be similar in both series, irrespective of the presence or absence of the additional hemiacetal function. In addition, the PLA2 inhibitory activity increases with the increasing hydrophobic character of the side chain linked to the pyranofuranone moiety. The most active compounds, FCA and FMA, carry a farnesyl residue linked to the pyranofuranone substructure. The most potent PLA2 inhibitor, FMA, was tested in the mouse carrageenan paw edema at the oral dose of 10 mg/kg and showed an activity similar to the reference antiinflammatory drug, indomethacin.

Microbial transformation of isoprenoid systems by means of fungi of Zoophthora genus--microbial transformation of compounds with alpha-campholenic system by means of fungus Zoophthora (Neopandora) sp.

Unsaturated ketones (4 and 10) and epoxides (2-3 and 8-9) were the main products of biotransformation performed by means of Zoophthora (Neopandora) phyllobii. Enantiospecificity of both reactions leading to these compounds strongly depends on the distance of reacting fragment of molecule from the chiral center at C-1'.

4-acetylaplykurodin B and aplykurodinone B, two ichthyotoxic degraded sterols from the Mediterranean mollusk Aplysia fasciata.

Two ichthyotoxic lactones, 4-acetylaplykurodin B [1] and aplykurodinone B [2], were isolated from the external parts of the body of the mollusk Aplysia fasciata. Their structures, determined by spectroscopic and chemical means, are closely related to aplykurodin B [3] previously isolated from Aplysia kurodai. The interconversion of delta- and gamma-lactones in the aplykurodin derivatives has been also investigated.

A novel multifunctional metabolic pathway in a marine mollusc leads to unprecedented prostaglandin derivatives (prostaglandin 1,15-lactones).

The discovery of high levels of prostaglandin (PG) 1,15-lactones of both the E and F series and their co-existence with PGs has been recently described in the opisthobranch mollusc Tethys fimbria. The present study was undertaken in order to investigate the biosynthesis of these novel natural PG derivatives in vivo using radiolabelled precursors, and to gain a preliminary understanding of their biological role. PGE2 1,15-lactone was shown to be produced from both PGE2 and PGF2 alpha in the mollusc mantle and appeared to be quickly transferred to the mollusc dorsal appendices (cerata). The detachment of the latter during the typical defence behaviour of T. fimbria was accompanied by the conversion of PGE2 and PGE3 1,15-lactones back to the corresponding PGs. Both PGE2 and PGE2 1,15-lactone were also shown to be biosynthesized from arachidonic acid. Lactones of the F series were present as 11-acetyl derivatives in T. fimbria mantle and as 9- and 11-fatty acyl esters in the mollusc egg-mass and reproductive gland, and their biosynthesis from PGF2 alpha was demonstrated in all of these tissues. A multiple biological role of PG 1,15-lactones in T. fimbria defensive behaviour, smooth muscle contraction and egg production/fertilization control is hypothesized. The high amounts of PG derivatives found in T. fimbria and the biosynthetic studies described herein indicate that this marine mollusc may be a useful model for future studies on PG biosynthesis.

A marine mollusc provides the first example of in vivo storage of prostaglandins: prostaglandin-1,15-lactones.

Prostaglandin-(PG) 1,15-lactones and, in smaller amounts, free acids, were isolated from both the mantle and the dorso-lateral appendices of the opisthobranch mollusc Tethys fimbria. In vivo conversion of PGs into the corresponding lactones and accumulation of PGE2- and PGE3-1,15-lactones in the appendages were shown. The detachment of these appendages from the molested mollusc caused the in vivo conversion of PGE2- and PGE3-lactones back to PGE2 and PGE3 respectively, thus providing the first example of a mechanism by which prostaglandins can be stored and, when needed, released.

[Cytomegalovirus and herpes simplex virus antibodies in patients with idiopathic ulcerative rectocolitis]. / Anticorpi per il virus citomegalico e per quello dell'herpes simplex in pazienti con rettocolite ulcerosa idiopatica.

The total and fractioned titres of circulating anticytomegalovirus (CMV) and antiherpesvirus (HSV) antibodies were evaluated in 63 idiopathic ulcerative proctocolitis patients in follow-up. The population was disaggregated applying criteria related to the stage of the disease: duration, extension, number of observed relapses over the follow-up. It was noted that just the anti-HSV antibodies were correlated in a statistically significant way to the extension (p less than 0.025) and duration (p less than 0.025) of the disease. We believe that this behaviour is a manifestation of the disease and that the antiHSV titration may be included in a score of evaluation during the follow-up.

Biosynthesis and metabolism of 9-[5'-deoxy-5'-(methylthio)-beta-D-xylofuranosyl]adenine, a novel natural analogue of methylthioadenosine.

The biosynthesis of 9-[5'-deoxy-5'-(methylthio)-beta-D-xylofuranosyl]adenine (xylosyl-MTA), a naturally occurring analogue of 5'-deoxy-5'-methylthioadenosine (MTA) recently characterized, was studied in the nudibranch mollusc Doris verrucosa. Experiments performed in vivo with putative labelled precursors such as [8-14C]adenine, [Me-14C]methionine and [Me-14C]MTA indicate that xylosyl-MTA originates from MTA. Experiments with MTA double-labelled at critical positions are consistent with a 3'-isomerization of the nucleoside through the formation of a 3'-oxo intermediate. In addition, experiments with the newly synthesized [3'-3H]xylosyl-MTA are indicative for a very low turnover rate of this molecule, which therefore accumulates in the mollusc.

Screening haemodialysis patients for infection with human immune deficiency virus (HIV).

A group of 484 patients having regular haemodialysis was tested for the presence of antibodies to the human immunodeficiency virus (HIV). With a commercial enzyme-linked immunoassay kit, the serum of 17 appeared positive. When these 17 samples were retested by a different method, however, none was found to contain antibodies to the virus. Furthermore, evaluation of the clinical state of these 17 patients for the presence of any prodromal symptoms associated with the acquired immune deficiency syndrome was negative. It is therefore suggested that patients having regular haemodialysis are presently at low risk of contracting infection by HIV. By contrast, 81% of these patients had antibodies to cytomegalovirus.

Insect antifeedant activity and hot taste for humans of selected natural and synthetic 1,4-dialdehydes.

The antifeedant activity towards larvae of Leptinotarsa decemlineata and Spodoptera littoralis and the hot taste for the human tongue have been determined for natural and synthetic 1,4-dialdehydes. Among the bicyclic dialdehydes the biological activity has been found to be dependent on the distance between the two aldehyde groups; tricyclic and pentacyclic dialdehydes are inactive in both tests. A short synthetic route to (-)- and (+)-polygodial is reported.

Minor and trace sterols from marine invertebrates 56. Novel coprostanols from the marine sponge Petrosia ficiformis.

Twelve stanols possessing the rare 5 beta-dihydro nucleus have been isolated from the marine sponge Petrosia ficiformis. These stanols have not previously been encountered in any samples of P. ficiformis which we have examined and appear to be the result of bacterial metabolism of the endogenous sponge sterols.

Dorid nudibranch elaborates its own chemical defense.

A biosynthetic experiment with mevalonic acid labeled with carbon-14 showed that the nudibranch Dendrodoris limbata elaborates polygodial, a sesquiterpenoid dialdehyde stored in the mantle, which constitutes its chemical defense against predators. Previously described nudibranchs drew defensive chemicals from their preys.

[A new method of quantitative analysis of bicarboxylic acids by means of gas chromatography]. / Un nuovo metodo di analisi quantitativa degli acidi bicarbossi lici mediante gas-cromatografia.

A new method for the quantitative extraction and esterification of dicarboxylic organic acids in aqueous solution and biological fluids has been developed. The acids are extracted and esterified in one step by using an Amberlite IRA 904 anion exange resin. The analyses of the methyl esters obtained have been performed by gas-liquid chromatography.

Metabolism in porifera. VII. Conversion of [7,7-3H2]-fucosterol into calysterol by the sponge Calyx niceaensis.

The sponge Calyx niceaensis metabolizes administered [7,7--(3)H2]-fucosterol to produce labelled calysterol, the principal sterol component of the sponge, possessing the unique feature of a cyclopropene ring bridging C23,24.