Test of "crab-waist" collisions at the DAPhiNE Phi factory.

The electron-positron collider DAPhiNE, the Italian Phi factory, has been recently upgraded in order to implement an innovative collision scheme based on large crossing angle, small beam sizes at the crossing point, and compensation of beam-beam interaction by means of sextupole pairs creating a "crab-waist" configuration in the interaction region. Experimental tests of the novel scheme exhibited an increase by a factor of 3 in the peak luminosity of the collider with respect to the performances reached before the upgrade. In this Letter we present the new collision scheme, discuss its advantages, describe the hardware modifications realized for the upgrade, and report the results of the experimental tests carried out during commissioning of the machine in the new configuration and standard operation for the users.

Dihydrochalcones and coumarins of Esenbeckia grandiflora subsp. brevipetiolata.

Six furoquinolines and five coumarins have been isolated from the roots of Esenbeckia grandiflora subsp. brevipetiolata. The leaves yielded two dihydrochalcones and two flavonol rhamnosides. One of the coumarins (5-senecioyl-xanthotoxin) and the dihydrochalcones are novel compounds and their structures were elucidated by spectroscopic methods. The comparison with the dihydrochalcones previously isolated from another subspecies, E. grandiflora subsp. grandiflora is also provided.

Three isoflavanones with cannabinoid-like moieties from Desmodium canum.

Three further derivatives of 5,7,2',4'-tetrahydroxy-6-methyl isoflavanone have been isolated from the root extract of Desmodium canum and assigned the structures 2,3-dihydro-5,7-dihydroxy-6-methyl-3-(1a,2,3,3a,8b,8c-hexahydro-6-hydroxy-1,1,3a-trimethyl-1H-4-oxabenzo[f]cyclobut[c,d]inden-7-yl)-4H-1-benzopyran-4-one (1) 2,3-dihydro-5,7-dihydroxy-6-methyl-3-(6a,7,8,10a-tetrahydro-3-hydroxy-6,6,9-trimethyl-6H-dibenzo[b,d]pyran-2-yl)-4H-1-benzopyran-4-one (2) 2,3-dihydro-5,7-dihydroxy-6-methyl-3-(3-hydroxy-6,6,9-trimethyl-6H-dibenzo[b,d]pyran-2-yl) 4H-1-benzopyran-4-one (3). The three compounds and the previously isolated chromene 4 all derive from the geranylated precursor 5 by a series of cannabinoid-like oxidative rearrangements.

In vivo and in vitro production of alkaloids by Haplophyllum patavinum.

A protocol for shoot induction from callus of Haplophyllum patavinum was established. Two known furoquinoline (skimmianine and haplopine), and three quinolone (edulinine, ribalinine and isoplatydesmine) alkaloids were isolated for the first time from plant material, callus and shoot cultures of this species. The structures of these compounds have been characterised on the basis of spectroscopic evidence.

Aryltetralin lignans: chemistry, pharmacology and biotransformations.

Podophyllotoxin derivatives like etoposide 7a, etophos 7b, and teniposide 7c are used clinically as potent chemotherapeutic agents for a variety of tumors including small cell lung carcinoma, testicular cancer, and malignant lymphoma. These compounds derived from a series of modifications which converted podophyllotoxin 1a from an entity that interacted with tubulin and blocks mitosis to one that induced a block in late S or early G2 by interacting with topoisomerase II. Synthetic studies on podophyllotoxin derivatives can be divided in four general approaches (the oxo-ester route, the digydroxy acid route, the tandem conjugate addition route and the Diels-Alder route). Albeit a number of synthetic sequences afforded products with excellent enantiopurities, the low overall yields still disqualify synthesis as an alternative for naturally produced materials. An alternative route based on the enzyme-catalyzed cyclization of synthetic intermediates to analogues of the podophyllotoxin family is being explored. Synthetic dibenzylbutanolides, which were revealed by biosynthetic studies to be the precursors of aryltetralin lignans, have been treated with enzymes derived from cell cultures of Podophyllum peltatum, Catharanthus roseus, Nicotiana sylvestris and Cassia didymobotrya. The ciclyzation process afforded however compounds with a different stereochemistry in the C ring. The obtainment of a novel compound with a bynzylidenebenzylbutirolactone structure still leaves considerable scope for exploring biotransformations in order to obtain podophyllotoxin analogues via a combination of synthetic chemistry and biotechnological methods.

Novel hypotensive agents from Verbesina caracasana. 8. Synthesis and pharmacology of (3,4-dimethoxycinnamoyl)-N(1)-agmatine and synthetic analogues.

The more polar metabolites from the Venezuelan plant Verbesina caracasana, i.e., N(3)-prenylagmatine, (3,4-dimethoxycinnamoyl)-N(1)-agmatine, agmatine, and galegine (prenylguanidine), previously reported (Delle Monache, G.; et al. BioMed. Chem. Lett. 1999, 9, 3249-3254), have been synthesized following a biosynthetic strategy. The pharmacologic profiles of various synthetic analogues of (3,4-dimethoxycinnamoyl)-N(1)-agmatine (G5) were also analyzed, to shed some light on the structure-activity relationship of these compounds. Derivatives with the (E)-configuration and/or with a p-methoxybenzoyl moiety were found to be responsible for higher hypotensive effects, which were associated with a slight and, in some cases, not dose-related increase of cardiac inotropism, with variable and not significant chronotopic responses, and, only at higher doses, with effects of respiratory depression. Either an increase (to six) or a decrease (to two) of the number of methylene groups in the alkyl chain of (E)-G5 did not change blood pressure responses, while slightly increasing the positive inotropic ones. At pharmacological doses, all the studied compounds showed hypotensive and slight positive inotropic effects without relevant chronotropic and respiratory actions.

Synthesis of both enantiomers of 4-vinyl oxazolidin-2-one from a single precursor: D-isoascorbic acid.

A convenient synthesis of (S)- and (R)-4-vinyl oxazolidin-2-one 1 and 2 from the same inexpensive starting material, D-isoascorbic acid, is described. The title compounds were obtained in 44% and 38% yield, respectively, by operationally simple steps. This approach is a suitable alternative to the literature methods and enhances the synthetic utility of these intermediates. Inc.

Further hypotensive metabolites from Verbesina caracasana.

After the isolation of caracasanamide and caracasandiamide, further hypotensive components of Verbesina caracasana were shown to be N3-prenylagmatine, N1-3',4'-dimethoxycinnamoylagmatine, agmatine and galegin (prenylguanidine). The structures were assigned on the basis of the spectral data of both metabolites and products from their alkaline hydrolyses. A pharmacological analysis of these products is also presented.

Purification and partial characterization of a peroxidase from plant cell cultures of Cassia didymobotrya and biotransformation studies.

An acidic peroxidase (EC 1.11.1.7) produced by cell suspension cultures of Cassia didymobotrya (wild senna) was purified from culture medium collected on the 29th day. The enzyme was shown to be a glycoprotein with a pI of 3.5, a molecular mass of approx. 43 kDa by SDS/PAGE and 50 kDa by gel filtration. The N-terminal sequence was very similar to those of other plant peroxidases. The peroxidase was characterized by a high specificity towards coniferyl alcohol and other natural phenolics such as guaiacol and ferulic and caffeic acids. These findings suggest that the enzyme is involved in lignification processes of the cell wall. Moreover, the enzyme was able to catalyse the oxidation of 4,3',4'-trihydroxychalcone and 4, 3',4'-trihydroxy-3-methoxychalcone to the corresponding 3, 3'-biflavanones, as mixtures of racemic and meso forms.

Histological study of callus formation and optimization of cell growth in Taxus baccata.

Callus growth of Taxus baccata was optimized when Murashige and Skoog or B5 media were used with 2,4-D/kinetin ratios of 1:0.1, 2:0.1, and 5:0.1, when statistically equivalent results were obtained. A cell suspension culture was successfully achieved with a 3-fold increase in fresh weight after 40 days. Histological examination showed that in the leaf explants both the epidermis and mesophyll tissues divided to produce callus. In the stem explants callus formation was due to the cell division of the cortical parenchyma and of the cambium.

Comparison between metabolite productions in cell culture and in whole plant of Maclura pomifera.

Plant tissue cultures of Maclura pomifera showed a metabolite accumulation pattern which was both quantitatively and qualitatively different from that of the parent plant. Triterpenes and flavonoids were isolated from callus and cell cultures, however, xanthones and stilbenes, which have been reported in the whole plant, were not found. Among the flavonoids, flavones and flavanones were produced preferentially by the suspended cells, but with the prenyl substituents exclusively on ring A, while the isoflavones did not show the 3',4'-dihydroxyl substitution pattern found in the products isolated from fruits. A new prenylated 6'-deoxychalcone was also isolated from the callus and cell cultures.

Novel hypotensive agents from Verbesina caracasana. 2. Synthesis and pharmacology of caracasanamide.

Caracasanamide, one of the hypotensive agents isolated from Verbesina caracasana, is a mixture of (Z)-1a and (E)-1b forms of 1-[(3,4-dimethoxycinnamoyl)amino]-4- [(3-methyl-2-butenyl)-guanidino]butane. The structure of (E)-caracasanamide (1b) was confirmed by high-yielding synthesis starting from N,N'-bis(tert-butoxycarbonyl)-S-methylisothiourea. The water-soluble Z-form of 1a, assayed by i.v. route in anesthetized rats at doses ranging from 50 to 1600 micrograms/kg body weight, was found to decrease blood pressure, to increase cardiac inotropism, respiratory frequency, and tidal volume, and to induce a very slight and not significant tachycardia. Higher doses determined respiratory depression and, in some cases, consequent cardiac arrest. The compound was shown to affect cardiovascular function by acting at the vascular level in inducing arterial vasodilation, by determining sympathetic hypotone through central neurogenic mechanisms, and by interacting with the cardiac beta 1-adrenoreceptors. The respiratory effects were independent of the cardiovascular ones. In lowering blood pressure, the compound was more potent than guanethidine and not less potent than reserpine and papaverine. (Z)-Caracasanamide may therefore be useful in the treatment of arterial hypertension of moderate degree.

Inhibition of adenosine 3',5'-cyclic monophosphate phosphodiesterase by flavonoids from licorice roots and 4-arylcoumarins.

Isoliquiritigenin, glabridin, licoarylcoumarin and licoricidin were identified as strong inhibitors of adenosine 3',5'-cyclic monophosphate (cAMP) phosphodiesterase in waste materials which were obtained during the industrial extraction of glycyrrhizin from licorice roots. The structure-activity relationships of 12 flavonoids from licorice roots and 34 4-arylcoumarins were studied. In 4-arylcoumarins, 5,7-dihydroxy derivatives were generally highly inhibitory towards cAMP phosphodiesterase.

[Role of non-invasive vascular diagnosis in the study of "diabetic foot"]. / Ruolo della diagnostica vascolare non invasiva nello studio del "piede diabetico".

The Authors examine the possibilities of instrumental diagnosis in patients with the "diabetic foot" syndrome. The lack of clinical relevance of the so called "microangiopathy" is stressed, because. Indeed, either the "macroangiopathy" or the diabetic neuropathy are responsible for almost all the symptoms of this syndrome. In the differential diagnosis between these two major sequelae of diabetes, with consequently wide differences in the therapeutic choices, the Doppler ultrasound examination has been of paramount usefulness, because it is very sensitive and specific in detecting and localizing any lesion suggestive of macroangiopathy.

Metabolites from in vitro cultures of Cassia didymobotrya.

From suspension cultures of Cassia didymobotrya 7-acetylchrysophanol, chrysophanol-physcion-l0,l0'-bianthrone, (E)- and (Z)-3'-hydroxy-3,4,5'-trimethoxystilbene, (E)-4,3'-dihydroxy-3,5'-dimethoxystilbene and 7,4'-dihydroxy-3,5,3'-trimethoxyflavone have been isolated along with several known metabolites.

[Hyponatremia in cirrhosis with ascites]. / L'iponatremia nel cirrotico con ascite.

Hyponatremia complicates ascitic hepatic cirrhosis with frequency and gravity related to the gravity of the cirrhosis itself. When hyponatremia develops, it worsens the already present secondary hyperaldosteronism and makes therapy with spironolactone inefficacious. From a pathophysiologic viewpoint a pathogenetic role in determining hyponatremia is attributable to the reduced plasmatic renal perfusion; in several patients a syndrome of inappropriate ADH secretion develops. Other neurohormonal systems (catecholamines, prostaglandins, natriuretic hormones) are probably very important in modifying renal hemodynamics and renal tubular function. In some patients a causative role for hyponatremia is attributable to iatrogenic factors (e.g.: diuretics). From a therapeutic viewpoint, we examine some schedules, pharmacologic or not, that, however, are far from being useful for all patients. We discuss, mainly, water restriction, osmotic diuretics with or without loop diuretics, loop diuretics followed by sodium reintegration and concentration-reinfusion of ascites or application of peritoneovenous shunt.

Thrombosis of congenital double popliteal vein: case report.

The authors present the case of a patient with phlebothrombosis of the left lower limb, not diagnosed with traditional ultrasonographic methods (Doppler c w) but recognized by the echo Doppler (duplex scanner) method. The diagnosis was made difficult by the presence of a congenital double left popliteal vein, with hypoechogenic thrombosis of only one of the two twin veins. The authors stress the diagnostic importance of the duplex scanner method in the study of the phlebobstructive pathologies of the lower limbs.