Disruptions of feather carotenoid pigmentation in a subset of hybrid northern flickers (Colaptes auratus) may be linked to genetic incompatibilities.

Hybridization can bring in single individuals alleles that were never designed to work together, which can result in unexpected or transgressive phenotypes. The Yellow-shafted (auratus group) and Red-shafted (cafer group) subspecies groups of the Northern Flicker (Colaptes auratus) differ conspicuously in the coloration of their flight feathers, but hybridize freely where their ranges overlap in western North America. The difference in color is largely the result of the Red-shafted form harboring ketolated products at C4(4') of the carotenoids found in the Yellow-shafted form. Characterizing the carotenoid pigments in a series of birds of intermediate color (presumed hybrids) revealed that most accumulated a product of ß-cryptoxanthin with a keto group on its hydroxylated ring (3-hydroxy-echinenone), while a few accumulated the product with a keto group on the unhydroxylated ring (3'-hydroxy-echinenone). Surprisingly, the latter group also had feather barbs that were noticeably yellower than the associated rachis, corresponding to a lower level of ketolation at C4(4'). We assessed possible biochemical explanations for the differences by probing the relative carotenoid concentration data in individuals of varying color. The difference between the hybrids could not be explained by the general level of ketolation of carotenoids or a particular selectivity of the 4-ketolase involved. We present a testable genetic explanation that invokes incompatibilities between divergent alleles of the two parental forms at interacting loci. Because the idiosyncrasies affect oxidation, they may be the product of mitonuclear incompatibilities.

Full spectroscopic characterization of two crystal pseudopolymorphic forms of the antiandrogen cortexolone 17α-propionate for topic application.

Cortexolone-17α-propionate (CP) is a topically active antiandrogen useful in the treatment of skin disorders. In the solid state, three anhydrous forms of this drug (CPI, CPII and CPIII) occur, together with one hydrated crystal (CPW). The single crystal structure of the monohydrated phase, CPW, compared with that of the anhydrous form CPIII, shows a markedly different solid state behavior. These latter pseudopolymorphic forms have also been fully characterized by spectroscopic methods.

Modified quaternary ammonium salts as potential antimalarial agents.

A series of new quaternary ammonium salts containing a polyconjugated moiety has been synthesized and characterized; their biological activity as potential antimalarial agents was investigated, as well. All compounds were screened against chloroquine resistant W-2 (CQ-R) and chloroquine sensitive, D-10 (CQ-S) strains of Plasmodium falciparum showing IC50 in the submicromolar range and low toxicity against human endothelial cells.

Plumage pigment differences underlying the yellow-red differentiation in the Northern Flicker (Colaptes auratus).

Elucidating the processes that create species differences is a central goal of evolutionary biology. The Northern Flicker (Colaptes auratus) exists as two well-differentiated subspecies groups in North America, the Yellow-shafted (auratus group) and Red-shafted Flickers (cafer group), which differ strikingly in the color of the underside and rachises of flight feathers, and of malar and nuchal patches. We investigated the physiological basis of these conspicuous phenotypic differences by identifying and quantifying the pigments involved. The yellow feathers of auratus contained carotenoids commonly found in nature (lutein, ß-cryptoxanthin, zeaxanthin and ß-carotene). The orange to red shafts/vanes of cafer and hybrids contained these carotenoids as well as mono- and diketo-carotenoids (notably adonirubin, α-doradexanthin, canthaxanthin, astaxanthin), representing oxygenated products at carbon C4(4') of the carotenoids present in auratus. Oxygenation of feather carotenoids at C4(4') correlated closely with shaft/vane redness. Carotenoid hydroxylation at C3(3') and the proportion of carotenoids with ε end-rings also varied with color and belie differences in the activity of several carotenoid-modifying enzymes between the two subspecies groups. Curiously, occasional yellow feathers in red-shafted individuals had the carotenoids of auratus, hence the differences are not constitutive in cafer, underscoring regulatory differences. The red malar stripe of cafer, the black malar stripe and red nuchal patch of auratus all contained similar types and amounts of carotenoids, mostly 3-hydroxy-4-keto-carotenoids. The biochemical differences between two strongly differentiated forms we uncovered shed light on how plumage coloration can change over evolutionary time and point to further avenues of research.

Structural elucidation of the Rifaximin Ph. Eur. Impurity H.

Rifaximin, a semisynthetic, rifamycin-based non-systemic antibiotic is used in the treatment of acute and chronic gastrointestinal disorders. The aim of this study was the elucidation of the molecular structure of the 802 Dalton impurity which was found in Rifaximin industrial batches and reported with an erroneous structure in European Pharmacopoeia 6.5 (2009) [7] monograph as Rifaximin Impurity H. This impurity was isolated from Rifaximin by preparative HPLC and purified by column chromatography. The molecular structure was evidenced by means of (1)H and (13)C NMR spectroscopy, mass spectrometry and FT-IR.

Estimation and characterisation of budesonide tablets impurities.

Budesonide is the 16alpha,17alpha-acetal of 16alpha-hydroxyprednisolone with n-butyraldehyde, endowed with anti-inflammatory activity. In a sample of budesonide tablets, kept for 3 years at 25 degrees C and 60% RH unknown impurities, not reported in European Pharmacopoiea, were present. Their identification was achieved by means of chemical and spectroscopic methods.

Structural elucidation of an unknown Simvastatin by-product in industrial synthesis starting from Lovastatin.

Unknown by-product in Simvastatin synthesis from Lovastatin was found. The elucidation of this molecular structure by means of (1)H and (13)C NMR spectroscopy, HPLC/MS, MS/MS and FT-IR was shown. The mentioned by-product, originated during Merck Sharp and Dhome synthesis scheme was isolated in the second-last step replacing butylamine with benzylamine. The spectroscopic results agreed with a molecular formula C(32)H(43)NO(3). The proposed structure of this compound, characterised by the presence of a conjugated dienic system in the heptanoic acid amide residue, was alpha,beta,gamma,delta unsaturated Simvastatin N-benzylamide.

Plumage carotenoids of the Pin-tailed Manakin (Ilicura militaris): evidence for the endogenous production of rhodoxanthin from a colour variant.

The Pin-tailed Manakin (Ilicura militaris) is a small, sexually dimorphic, frugivorous suboscine songbird (Pipridae; Passeriformes; Aves) endemic to the Atlantic Forest of Brazil. A variant individual of this species was recently described in which the red patches that characterise the male's Definitive plumage were replaced by orange-yellow ones. We show here that the pigments in the feathers of the colour variant are common dietary carotenoids (zeaxanthin, beta-cryptoxanthin), not carotenoids synthesised by birds, lending support to the suggestion that the individual is a colour mutant lacking the capability to transform yellow dietary pigments into the red pigments normally present in these feathers. By comparison, the yellow crown feathers of a close relative, the Golden-winged Manakin (Masius chrysopterus), contained predominantly endogenously produced epsilon-caroten-3'-ones. Surprisingly, the normal-coloured feathers of the male Pin-tailed Manakin owe their red hue to rhodoxanthin, an unusual carotenoid more commonly found in plants, rather than 4-keto-carotenoids typically found in red plumages and found lacking in previously characterised bird colour variants. The implication is that birds, like the tilapia fish, may be able to synthesise this unusual pigment endogenously from dietary precursors. A newly described carotenoid, 6-hydroxy-epsilon,epsilon-carotene-3,3'-dione, here named piprixanthin, present in the red feathers of the Pin-tailed Manakin, provides a plausible intermediate between epsilon,epsilon-carotene-3,3'-dione (canary-xanthophyll B), a bright yellow pigment found in this and other songbirds, and rhodoxanthin. It is apparent that pigeons (Columbidae, Columbiformes) also have the capability to produce rhodoxanthin, and a structurally related pigment, endogenously. The ability to synthesise rhodoxanthin might have arisen at least twice in birds.

Quantitative determination of amorphous cyclosporine in crystalline cyclosporine samples by Fourier transform infrared spectroscopy.

The purpose of this study is the development of a quantification method to detect the amount of amorphous cyclosporine using Fourier transform infrared (FTIR) spectroscopy. The mixing of different percentages of crystalline cyclosporine with amorphous cyclosporine was used to obtain a set of standards, composed of cyclosporine samples characterized by different percentages of amorphous cyclosporine. Using a wavelength range of 450-4,000 cm(-1), FTIR spectra were obtained from samples in potassium bromide pellets and then a partial least squares (PLS) model was exploited to correlate the features of the FTIR spectra with the percentage of amorphous cyclosporine in the samples. This model gave a standard error of estimate (SEE) of 0.3562, with an r value of 0.9971 and a standard error of prediction (SEP) of 0.4168, which derives from the cross validation function used to check the precision of the model. Statistical values reveal the applicability of the method to the quantitative determination of amorphous cyclosporine in crystalline cyclosporine samples.

Carotenoid concentration in barn swallow eggs is influenced by laying order, maternal infection and paternal ornamentation.

Carotenoids are critical to embryonic development, immunity and protection from oxidative stress. Transmission of carotenoids to the eggs may affect development and maturation of immunity in offspring, but carotenoids may be available to females in limiting amounts. Females may thus transfer carotenoids to the eggs differentially in relation to the reproductive value of the offspring as affected by sexual ornamentation of their father. In this study of maternal allocation of carotenoids to the eggs in the barn swallow (Hirundo rustica), females whose immune system had been experimentally challenged with an antigen had smaller lutein concentrations in their eggs than controls. We manipulated the size of a secondary sexual character (tail length) of males, and analysed the effect of manipulation on allocation of lutein to eggs by their vaccinated mates. Contrary to our prediction based on parental allocation theory, mates of tail-shortened males had a larger lutein concentration in their eggs compared with those of control and tail-elongated males. According to previous studies, offspring of short-tailed males have larger exposure and/or susceptibility to parasites. A larger lutein concentration in the eggs of females mated to males with experimentally reduced ornaments may thus reflect adaptive maternal strategies to enhance offspring viability.

Carotenoid Plasma Concentration, Immune Profile, and Plumage Ornamentation of Male Barn Swallows (Hirundo rustica).

Carotenoids exert immunomodulating, immunostimulating, and antioxidant actions in mammals and are major determinants of coloration in animals. Honest advertisement models of sexual selection propose that male ornaments, including coloration, are reliable indicators of male quality. Because of their simultaneous effects on male coloration and immunity, carotenoids might mediate the hypothesized relationship between the expression of epigamic coloration and parasitism in vertebrates. We analyzed the relationship between immune profile and concentration of lutein, the most abundant carotenoid in the plasma of male barn swallows (Hirundo rustica). Consistent with our predictions, lutein plasma concentration was negatively correlated with gamma-globulin plasma levels and concentration of selected leukocyte types in peripheral blood, suggesting that, to exert immune function, carotenoids are taken up from plasma, thus becoming unavailable for epigamic signaling. The coloration of red feathers of the throat of adult males was positively related to plasma concentration of lutein, but not with immunologic variables, consistent with the idea that more brightly colored males do not pay a larger immunological cost for their coloration compared with less brightly colored males. Length of male tail ornaments, which is currently under directional sexual selection, was positively correlated with lutein plasma levels. In species where carotenoids limit immune function, demands for pigments for sexual signaling might compete with those for immunity, thus generating a mechanism that enforces honesty on the signal.