Studies on the Biosynthesis of Psoralen and Bergapten in the Leaves of Ficus carica

With the aim of studying the biosynthesis of psoralen and bergapten, two furocoumarins present in the leaves of "Ficus carica" (Moraceae), the Authors, continuing preceding researchs on this topic, have fed the leaves with the following labelled precursors: 4′,5′-dihydropsoralen, 4′,5′-dihydrobergapten, 7-hydroxycoumarin, 5,7-dihydroxycoumarin and 5-methoxy-7-hydroxycoumarin. The results obtained indicate that all these substances are certain biogenetic precursors for psoralen and bergapten. On the basis of the results obtained the biosynthetic pathway of furocoumarins seems to involve first of all the formation of a coumarinic derivative 7-hydroxylated, then an isoprenylation reaction which leads to the formation of the hydrogenated furan ring, finally dehydrogenation of the 4′,5′-dihydrofurocoumarins to psoralen and bergapten

Studies on the Biosynthesis of Some Furocoumarins Present in Ruta graveolens

The biosynthesis of some furocoumarins present in Ruta graveolens has been studied administering labeled psoralen, xanthotoxin, rutaretin, marmesin and 7-hydroxycoumarin-derivatives. The results obtained indicate that the biosynthetic pathway involves not only psoralen, but also xanthotoxin and bergapten, by means of methoxylation or demethoxylation reactions. Moreover results achieved from administering rutaretin demonstrate that this substance is a new very effective natural precursor for xanthotoxin; in a parallel way marmesin is incorporated into psoralen. The reported results indicate that also at the stage of natural 4′,5′-dihydrofurocoumarins intermediates an interconversion can occur. Finally the essential role of umbelliferone in the biosynthesis of furocoumarins has been confirmed

The Phototoxicity of Fluvastatin, an HMG-CoA Reductase Inhibitor, Is Mediated by the formation of a Benzocarbazole-Like Photoproduct

In this paper, we have investigated the mechanism of phototoxicity of fluvastatin, an 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, in human keratinocytes cell line NCTC-2544. Fluvastatin underwent rapid photodegradation upon Ultraviolet-A (UVA) irradiation in buffered aqueous solution as shown by the changes in absorption spectra. Interestingly, no isosbestic points were observed but only a fast appearance of a spectral change, indicative of the formation of a new chromophore. The isolation and characterization of the main photoproduct revealed the formation of a polycyclic compound with a benzocarbazole-like structure. This product was also evaluated for its phototoxic potential. Cell phototoxicity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide test after 72 h from the irradiation in the presence of fluvastatin. The results showed a reduction of the cell viability in a concentration and UVA dose-dependent manner. Surprisingly, the photoproduct showed a dramatic decrease of the cell viability that occurred at concentrations of an order of magnitude lower than the parent compound. Flow cytometric analysis indicated that fluvastatin and its main photoproduct induced principally necrosis as revealed by the large appearance of propidium iodide-positive cells and confirmed also by the rapid drop in cellular adenosine triphosphate levels. Interestingly, a rapid increase of intracellular calcium followed by an extensive cell lipid membrane peroxidation and a significant oxidation of model proteins were induced by fluvastatin and its photoproduct, suggesting that these compounds exerted their toxic effect mainly in the cellular membranes. On the basis of our results, the phototoxicity of fluvastatin may be mediated by the formation of benzocarbazole-like photoproduct that acts as strong photosensitizer

Difurocoumarins, Psoralen Analogs: Synthesis and DNA Photobinding

A new tetracyclic derivative, difurocoumarin, was synthesized and studied in order to ascertain its possible use as a photochemotherapeutic agent alternative to psoralens. The compound proved able to photobind monofunctionally to DNA on irradiation with UV-A. A photocycloadduct with thymine was isolated and characterized spectroscopically

"Delirium Day": A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 \ub1 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys