Biological activity of parrodienes, a new class of polyunsaturated linear aldehydes similar to carotenoids.

A new chemical named parrodienes has been extracted from parrots' plumage. From the chemical point of view, parrodienes are polyunsaturated aldehydes similar to carotenoids. On the basis of this similarity we organized some biological experiments to evaluate the inhibition of lipoperoxidation of cell membranes induced by CCl4, protection against ultraviolet rays, anti-inflammatory activity and protection from an increase of ornithine-decarboxylase as marker of tumoral skin alteration. The results of these experiments showed that unsaturated dienes (parrodienes) play an important role on the inhibition and prevention of many biological processes that are at the basis of different pathological disorders.

Structural characterization of a dipeptide compound with immunostimulant activity: 3-(5-thioxo-L-prolyl)-L-thiazolidine-4-carboxylic acid.

The structural characteristics of an immunostimulating agent (3-(5-thioxo-L-prolyl)-L-thiazolidine-4-carboxylic acid) have been established using a combination of 1H and 13C NMR spectroscopy, molecular mechanic calculations (in vacuo and in solution) and X-ray crystallographic analyses. Conformational calculations and NMR spectra identify two classes of conformers, cis and trans, around the peptide bond between the rings, while in the solid state only the cis form has been found.

Evaluation of the antioxidant activity of new carotenoid-like compounds by electron paramagnetic resonance.

The antioxidant activity of a novel series of derivatives with a carotenoid-like structure was studied. These derivatives have recently been isolated chemically as a result of studies on the pigments present in a particular species of birds, namely parrots. These novel derivatives, which are also called parrodienes, have been proved to possess interesting biological properties that differ from those that carotenoids are known to have. The objective of this study was to demonstrate the ability of these novel compounds to inhibit the formation of reactive oxygen species, especially their ability to block the formation of hydroxyl radicals, which are among the most reactive products of oxygen reactions and which produce the greatest damage to cells and tissues. The technique used to assess this antioxidant capacity of parrodienes was electron paramagnetic resonance, which allows direct assessment of inhibition of hydroxyl radical formation (.OH). The results show that these derivatives, especially octatriene, are able to exert evident antioxidant activity, thus confirming that their antioxidant properties are important for their biological activity.

The effect of dietary carotenoid access on sexual dichromatism and plumage pigment composition in the American goldfinch.

We investigated potential dietary and biochemical bases for carotenoid-based sexual dichromatism in American goldfinches (Carduelis tristis). Captive male and female finches were given access to the same type and amount of carotenoid pigments in the diet during their nuptial molt to assess differences in the degree to which the two sexes incorporated ingested pigments into their plumage. When birds were fed a uniform, plain-seed diet, or one that was supplemented with the red carotenoid canthaxanthin, we found that males grew more colorful plumage than females. HPLC analyses of feather pigments revealed that male finches incorporated a higher concentration of carotenoids into their pigmented feathers than females. Compared to females, males also deposited significantly more canary xanthophyll B into feathers when fed a plain-seed diet and a greater concentration and proportion of canthaxanthin when fed a carotenoid-supplemented diet. These results indicate that sex-specific expression of carotenoid pigmentation in American goldfinches may be affected by the means by which males and females physiologically utilize (e.g. absorb, transport, metabolize, deposit) carotenoid pigments available to them in the diet.

The influence of carotenoid acquisition and utilization on the maintenance of species-typical plumage pigmentation in male American goldfinches (Carduelis tristis) and northern cardinals (Cardinalis cardinalis).

Birds display a tremendous variety of carotenoid-based colors in their plumage, but the mechanisms underlying interspecific variability in carotenoid pigmentation remain poorly understood. Because vertebrates cannot synthesize carotenoids de novo, access to pigments in the diet is one proximate factor that may shape species differences in carotenoid-based plumage coloration. However, some birds metabolize ingested carotenoids and deposit pigments that differ in color from their dietary precursors, indicating that metabolic capabilities may also contribute to the diversity of plumage colors we see in nature. In this study, we investigated how the acquisition and utilization of carotenoids influence the maintenance of species-typical plumage pigmentation in male American goldfinches (Carduelis tristis) and northern cardinals (Cardinalis cardinalis). We supplemented the diet of captive goldfinches with red carotenoids to determine whether males, which are typically yellow in color, were capable of growing red plumage. We also deprived cardinals of red dietary pigments to determine whether they could manufacture red carotenoids from yellow precursors to grow species-typical red plumage. We found that American goldfinches were able to deposit novel pigments in their plumage and develop a striking orange appearance. Thus, dietary access to pigments plays a role in determining the degree to which goldfinches express carotenoid-based plumage coloration. We also found that northern cardinals grew pale red feathers in the absence of red dietary pigments, indicating that their ability to metabolize yellow carotenoids in the diet contributes to the bright red plumage that they display.

The chemical structure of the pigments in Ara macao plumage.

Parrots (Psittaciformes) harbor unusually bright, non-carotenoid, feather pigments. We successfully extracted and purified a sufficient quantity of pigment from the red plumage of the Scarlet Macaw (Ara macao) for a partial chemical analysis. The extracts were analyzed by HPLC coupled with UV-VIS and mass spectroscopy before and after total hydrogenation. We found at least four pigment components. We propose a linear polyenal structure comparable with the molecules tetradecahexenal, hexadecaheptenal, octadecaoctenal and eicosanonenal.

Carotenoids in bird plumage: the complement of red pigments in the plumage of wild and captive bullfinch (Pyrrhula pyrrhula).

We have studied the carotenoid pigments in the red plumage of male bullfinch (Pyrrhula pyrrhula) immediately following capture and after the completion of the moult in captivity under dietary control. Astaxanthin, adonirubin, and alpha-doradexanthin, as well as papilioeritrinone and canthaxanthin (in lower amounts) are in every case the dominant carotenoids in the plumage pigment of wild individuals. alpha-Doradexanthin is responsible for the reddish-rose colour, which captive individuals adopt after a diet consisting mainly of lutein as disposable carotenoid. The red pigmentation biogenesis of captive bullfinch is compared with those of other red pigmented Carduelinae in which male individuals usually lose the red colour in captivity, namely Carpodacus roseus, Carpodacus rubricilloides, Uragus sibiricus, Carduelis cannabina, Carduelis flammea, Loxia curvirostra and Pinicola enucleator.

Synthesis of purine derivatives of potential immunomodulatory activity.

Moving from the interest as immunomodulatory agent of ST789 was studied the synthesis of series of N9alkylated hypoxanthine and adenine. The synthesis and the chemical physical properties of these derivatives are here described.

Determination of substances of abuse in biological fluids by GC/MS using chemical ionization with acetonitrile.

GC/ms is an important method to determine drugs in biological fluids. For each of the most commonly used drugs a methanolic solution (100 micrograms/ml) was prepared; 30 microliters of each solution was evaporated using nitrogen flow and than diluted in 100 microliters of a derivatizing mixture constituted by MSTFA and toluene (30/70). After a short reaction time at room temperature 1 ml of each solution was injected into a SE-52 column (15 m x 0.25 mm) using chemical ionization with acetonitrile. This method has a good signal/noise ratio and is very useful in screening techniques.

Comparison of clinical and psychologic features of fibromyalgia and masticatory myofascial pain.

The aim of this study was to investigate common symptoms and divergent features in fibromyalgia (FS) and masticatory myofascial pain (MFP) in patients affected by craniomandibular disorders. Twenty-three women with MFP and 23 women with FS were studied. All patients were examined by a dentist and by a rheumatologist. Craniomandibular disorders were assessed with a subjective symptoms questionnaire, detailed history interview, joint function examination, and manual palpation of masticatory and cervical muscles. The Middlesex Hospital Questionnaire was used to obtain personality profiles of the patients. The craniomandibular disorders questionnaire revealed various similarities in the two groups, the most striking of which were pain during mandibular function, articular noises, and headache. Both groups had muscle pain upon palpation; the mean scores (on a 0 to 4 scale) did not differ significantly between the two groups and ranged between 1.39 (SD 1.2) and 2.86 (SD 0.75). The mean value of active mouth opening was 40.9 mm (SD 9.1) in MFP patients and 44.6 mm (SD 7.2) in FS patients, while the mean value of passive opening was 49.6 mm (SD 6.0) in MFP patients and 49.8 mm (SD 3.5) in FS patients. These values did not differ significantly between the two groups, but did differ from the normal population, similar to the trend of the psychologic profile. The authors conclude that the physician should be alert to the need to conduct interdisciplinary evaluations in the diagnosis and management of FS and of MFP.

Evaluation of kinetic parameters of natural phytoalexin in resveratrol orally administered in wine to rats.

In view of the increasing interest in the biological activity of resveratrol, one of the components of red wine which is considered to be one of the main ingredients responsible for the beneficial effect of wine on human health, we have studied plasma kinetics and tissue bioavailability of this compound after red wine oral administration in rats. Plasma pharmacokinetics after oral administration of resveratrol could be described by an open one- or two-compartment model. Tissue concentrations show a significant cardiac bioavailability, and a strong affinity for the liver and kidneys.

Stability of resveratrol over time and in the various stages of grape transformation.

Research has been carried out with the purpose of verifying whether the resveratrol content in the skins or pomace of grapes stored for a long period of time without any particular protection with regard to temperature and humidity, could lead to a reduction of the content of this product detected at the beginning of the processing of grapes in vinification procedures. The dosages carried out both on the grape skin and on the pomace taken after fermentation and stored for a certain period of time, as well as on the products derived from alcoholic distillation, did not show the expected alterations in resveratrol content, considering their storage in bad environmental conditions for a long period of time. The results obtained confirm that resveratrol, unlike anthocyanins and other polyphenols, is stable and stores well over time.

Plasma, urine and tissue levels of trans- and cis-resveratrol (3,4',5-trihydroxystilbene) after short-term or prolonged administration of red wine to rats.

The aim of the present study was to evaluate the absorption, the concentration in different organs and the excretion of natural trans- and cis-resveratrol after red wine oral administration to rats. A first group of animals was given a dose of 4 ml of red wine containing 6.5 mg/l of total resveratrol. The animals were sacrificed at different time intervals. A second group of rats was given a daily dose of 2 ml of red wine containing 6.5 mg/l of total resveratrol for fifteen days. Total resveratrol concentrations were measured in plasma, urine, heart, liver and kidney. Even though the amount of resveratrol found in these different tissues was lower than that required for pharmacological activity, it is possible that prolonged administration of red wine in the diet could lead to an increased resveratrol concentration in different tissues and this could explain its suggested beneficial role against coronary heart disease.

Kinetics of trans- and cis-resveratrol (3,4',5-trihydroxystilbene) after red wine oral administration in rats.

Kinetics of trans- and cis-resveratrol (3,4',5-trihydroxystilbene), a natural compound from grape products, have been evaluated in rats after oral administration of red wine. Resveratrol concentrations were measured in plasma, heart, liver and kidneys. Tissue concentrations showed a significant cardiac bioavailability and strong affinity for liver and kidneys.

Separation and identification of carotenoids in bird's plumage by high-performance liquid chromatography--diode-array detection.

The coloured feathers of Carduelis spinus (Siskin), C. flammea (Redpoll), Serinus serinus (Serin), Loxia curvirostra (Crossbill), Pinicola enucleator (Grossbeak), Carpodacus roseus (Pallas Rosefinch) and Pyrrhula pyrrhula (Bullfinch) have been extracted with a new procedure using mild conditions (a few minutes at room temperature). After the separation of melanines and proteins, the extracts were analyzed by HPLC-MS and HPLC-UV-Vis. The main components of the pigments were identified in all the species examined; moreover, UV-Vis and MS data were collected also for the minor components. These data suggest that minor components are generally cis isomers accompanying the predominant all-trans isomers.

Synthetic biological response modifiers. Part II. Synthesis and immunomodulatory properties of some: N2-[omega-(pyrimidin-1-yl)carboxyalkyl]-L-arginines.

The synthesis and chemical and physical properties of some N2-[omega-(pyrimidin-1-yl)carboxyalkyl]-L-arginines are here described. Experiments of immunopharmacological evaluations are also described.

Analytical and chemical profile of pidotimod.

Pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl)carbonyl]-thiazolidine- 4-carboxylic acid, PGT/1A, CAS 121808-62-6) is a new synthetic immunostimulant, which has proved to possess a high activity. This paper describes its physico-chemical properties, structural identification including polymorphism, detection of impurities, determination of related compounds, separation, quantification and purity assay using high-performance liquid chromatography (HPLC).

ST 789 and ST 789 analogs: synthesis and analytical profile.

The procedure followed for the preparation of ST 789 and a series of origin derivatives analogs to ST 789 are described. A complete analytical profile of ST 789 and a concise profile of its analogs are also reported, together the purification methods applied.

A new peptide analog (RM06) modulates the growth of hematopoietic cells.

The bombesin carboxy terminal dipeptide Leu-Met, was bound to hypoxanthine with a pentoxy-carbonyl chain. The new purine derivative, N-omega-[5(1,6-dihydro-6-oxo-9-purinyl)] pentoxy-carbonyl-L-leucil-L- methionine-COOH (RM06), significantly augmented human bone-marrow derived granulocyte-monocyte colony forming units (CFU-GM) when added to the cell-culture medium. Moreover, in vivo hemopoietic reconstitution was more rapid in lethally irradiated bone-marrow reconstituted BDF-1 mice, treated with RM06. Both in vitro and in vivo effects were similar to those exerted by recombinant granulocyte-monocyte colony stimulating factor (GM-CSF). It is concluded that the new modified dipeptide modulates the growth of both human and murine hematopoietic cells in vitro and in vivo.

Effect of a new peptidyl-hypoxanthine derivative on natural killer cells and antitumor activity.

A new immunomodifier, [omega-(hypoxanthin-9-yl) pentoxy-carbonyl-leucyl-methionine] (RM06), was synthesized and its effect was evaluated on the activity of Natural Killer (NK) cells. Results indicate that RM06 is able to boost the NK activity of normal mice as well as to augment the regeneration of NK activity of lethally irradiated mice transplanted with syngeneic bone marrow (BM). This later effect also correlated with a significant increase in anti-tumor activity as evaluated by the resistance to metastasis in mice injected with syngeneic melanoma cells. These data indicate that RM06 is able to modulate the NK cell activity as well as the antitumor resistance.