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Dihydroxy bile acids, such as chenodeoxycholic acid (CDCA), are well known to promote colonic fluid and electrolyte secretion, thereby causing diarrhoea associated with bile acid malabsorption. However, CDCA is rapidly metabolised by colonic bacteria to ursodeoxycholic acid (UDCA), the effects of which on epithelial transport are poorly characterised. Here, we investigated the role of UDCA in the regulation of colonic epithelial secretion. Cl(-) secretion was measured across voltage-clamped monolayers of T84 cells and muscle-stripped sections of mouse or human colon. Cell surface biotinylation was used to assess abundance/surface expression of transport proteins. Acute (15 min) treatment of T84 cells with bilateral UDCA attenuated Cl(-) secretory responses to the Ca(2+) and cAMP-dependent secretagogues carbachol (CCh) and forskolin (FSK) to 14.0 ± 3.8 and 40.2 ± 7.4% of controls, respectively (n = 18, P < 0.001). Investigation of the molecular targets involved revealed that UDCA acts by inhibiting Na(+)/K(+)-ATPase activity and basolateral K(+) channel currents, without altering their cell surface expression. In contrast, intraperitoneal administration of UDCA (25 mg kg(-1)) to mice enhanced agonist-induced colonic secretory responses, an effect we hypothesised to be due to bacterial metabolism of UDCA to lithocholic acid (LCA). Accordingly, LCA (50-200 μm) enhanced agonist-induced secretory responses in vitro and a metabolically stable UDCA analogue, 6α-methyl-UDCA, exerted anti-secretory actions in vitro and in vivo. In conclusion, UDCA exerts direct anti-secretory actions on colonic epithelial cells and metabolically stable derivatives of the bile acid may offer a new approach for treating intestinal diseases associated with diarrhoea.

The fruitful collaboration between the High Commission for the Erbil Citadel Revitalization, the Italian Cooperation Project of MAE-IsIAO and the Italian Archaeological Mission in Iraqi Kurdistan of Sapienza, University of Rome & IsIAO allowed to carry out a series of activities aimed at the study and documentation of the Citadel of Erbil. The main activities consist in a set of geophysical prospections with Ground Penetrating Radar and in a topographic survey of the Citadel, which has provided the basis for a GIS platform, essential for managing the collected data. These activities are still ongoing, and preliminary results are extremely interesting. The GIS platform and the topographic data proved to be crucial for a proper documentation of the site and the data obtained from the prospections, in addition to confirming the existence of a complex archaeological stratigraphy, provide interesting clues about the presence of large defensive structures.

We report on the relationship between the structure-pharmacokinetics, metabolism, and therapeutic activity of semisynthetic bile acid analogs, including 6α-ethyl-3α,7α-dihydroxy-5β-cholan-24-oic acid (a selective farnesoid X receptor [FXR] receptor agonist), 6α-ethyl-23(S)-methyl-3α,7α,12α-trihydroxy-5β-cholan-24-oic acid (a specific Takeda G protein-coupled receptor 5 [TGR5] receptor agonist), and 6α-ethyl-3α,7α-dihydroxy-24-nor-5β-cholan-23-sulfate (a dual FXR/TGR5 agonist). We measured the main physicochemical properties of these molecules, including ionization constants, water solubility, lipophilicity, detergency, and protein binding. Biliary secretion and metabolism and plasma and hepatic concentrations were evaluated by high-pressure liquid chromatography-electrospray-mass spectrometry/mass spectrometry in bile fistula rat and compared with natural analogs chenodeoxycholic, cholic acid, and taurochenodexycholic acid and intestinal bacteria metabolism was evaluated in terms of 7α-dehydroxylase substrate-specificity in anaerobic human stool culture. The semisynthetic derivatives detergency, measured in terms of their critical micellar concentration, was quite similar to the natural analogs. They were slightly more lipophilic than the corresponding natural analogs, evaluated by their 1-octanol water partition coefficient (log P), because of the ethyl group in 6 position, which makes these molecules very stable toward bacterial 7-dehydroxylation. The hepatic metabolism and biliary secretion were different: 6α-ethyl-3α,7α-dihydroxy-5β-cholan-24-oic acid, as chenodeoxycholic acid, was efficiently conjugated with taurine in the liver and, only in this form, promptly and efficiently secreted in bile. 6α-Ethyl-23(S)-methyl-3α,7α,12α-trihydroxy-5β-cholan-24-oic acid was poorly conjugated with taurine because of the steric hindrance of the methyl at C23(S) position metabolized to the C23(R) isomer and partly conjugated with taurine. Conversely, 6α-ethyl-3α,7α-dihydroxy-24-nor-5β-cholan-23-sulfate was secreted in bile unmodified and as 3-glucuronide. Therefore, minor structural modifications profoundly influence the metabolism and biodistribution in the target organs where these analogs exert therapeutic effects by interacting with FXR and/or TGR5 receptors.

As from 1998 investigation at Barikot was extended to the hill, with its crescent moon shape protectively rising above the area of the ancient city, constituting natural defence on the north side. The earliest material dates back to the 2nd millennium B.C., although the earliest conserved structures belong to the 1st-2nd century A.D. Evidence suggesting that the two natural terraces on the hilltop constituted the Acropolis of the Indo-Greek city can be seen in the traces of a sturdy masonry structure that was plundered for material to build the subsequent structures, and that probably corresponds with a stretch of the city wall. The most spectacular utilisation was achieved around the 7th century AD when the eastern terrace was extended with a tall and solid substruction wall for the construction of a monumental sacred complex that dominated the valley.

In the fall of 2012 the Italian Archaeological Mission in the Iraqi Kurdistan signed an agreement with the Sulaimaniyah Antiquities Directorate, for creating the Archaeological Map of the area surrounding the Sasanian monument of Paikuli. In the course of the four campaigns, which have been carried out, the team has started to survey the area, has developed a methodology for the classification of ceramic materials and started the preliminary study of the findings. Furthermore, in 2013 MAIKI commenced an ethnographic research aimed at studying the religious heritage of the area.

Rapporto di scavo del sito 77 nella valle di Tang-e Bolaghi, Pasargade (Fars, Iran).

Dihydroxy bile acids, such as chenodeoxycholic acid (CDCA), are well known to promote colonic fluid and electrolyte secretion, thereby causing diarrhoea associated with bile acid malabsorption. However, CDCA is rapidly metabolised by colonic bacteria to ursodeoxycholic acid (UDCA), the effects of which on epithelial transport are poorly characterised. Here, we investigated the role of UDCA in the regulation of colonic epithelial secretion. Cl(-) secretion was measured across voltage-clamped monolayers of T84 cells and muscle-stripped sections of mouse or human colon. Cell surface biotinylation was used to assess abundance/surface expression of transport proteins. Acute (15 min) treatment of T84 cells with bilateral UDCA attenuated Cl(-) secretory responses to the Ca(2+) and cAMP-dependent secretagogues carbachol (CCh) and forskolin (FSK) to 14.0 ± 3.8 and 40.2 ± 7.4% of controls, respectively (n = 18, P0.001). Investigation of the molecular targets involved revealed that UDCA acts by inhibiting Na(+)/K(+)-ATPase activity and basolateral K(+) channel currents, without altering their cell surface expression. In contrast, intraperitoneal administration of UDCA (25 mg kg(-1)) to mice enhanced agonist-induced colonic secretory responses, an effect we hypothesised to be due to bacterial metabolism of UDCA to lithocholic acid (LCA). Accordingly, LCA (50-200 μm) enhanced agonist-induced secretory responses in vitro and a metabolically stable UDCA analogue, 6α-methyl-UDCA, exerted anti-secretory actions in vitro and in vivo. In conclusion, UDCA exerts direct anti-secretory actions on colonic epithelial cells and metabolically stable derivatives of the bile acid may offer a new approach for treating intestinal diseases associated with diarrhoea.

BackgroundCurcuma extract exerts a myorelaxant effect on the mouse intestine. In view of a possible use of curcuma extract in motor functional disorders of the gastrointestinal tract, a safety profile study has been carried out in the mouse.MethodsThirty mice were used to study the in vitro effect of curcuma on gallbladder, bladder, aorta and trachea smooth muscular layers and hearth inotropic and chronotropic activity. The myorelaxant effect on the intestine was also thoroughly investigated. Moreover, curcuma extract (200 mg/Kg/day) was orally administered to twenty mice over 28 days and serum liver and lipids parameters were evaluated. Serum, bile and liver bile acids qualitative and quantitative composition was were also studied.ResultsIn the intestine, curcuma extract appeared as a not competitive inhibitor through cholinergic, histaminergic and serotoninergic receptors and showed spasmolytic effect on K(+) induced contraction at the level of L type calcium channels. No side effect was observed on bladder, aorta, trachea and heart when we used a dose that is effective on the intestine. An increase in gallbladder tone and contraction was observed. Serum liver and lipids parameters were normal, while a slight increase in serum and liver bile acids concentration and a decrease in bile were observed.ConclusionsAlthough these data are consistent with the safety of curcuma extract as far as its effect on the smooth muscular layers of different organs and on the heart, the mild cholestatic effect observed in absence of alteration of liver function tests must be further evaluated and the effective dose with minimal side effects considered.

The Citadel of Erbil is the geographical, historical and cultural heart of the new Kurdish Regional Government of Iraq. This site is considered to be one of the most important sites of the entire Middle East, continuously inhabited over several millennia, and a request for its inclusion in the UNESCO list of World Heritage Site has been recently submitted. As part of the Italian Cooperation Project "Protection and promotion of the cultural heritage of the region of Kurdistan in Iraq" of the Department of Classics of Sapienza, University of Rome, training courses and activities of training on the job for the staff of the High Commission for the Erbil Citadel Revitalization have been organized. Activities include a) training in topography, archaeological methodology and architectural restoration; b) training on the job aimed at the creation of a topographical map of the Citadel; and c) a geophysical survey of the Citadel to understanding of the tell’s archaeological stratigraphy. The completion of a topographic map is functional to the documentation of the complex, since it will provide the frame in which the collected data will be set and a useful support for the GIS platform. Geophysical survey has highlighted the presence of significant structures positioned at different depths; at the present stage of our work their dating remains uncertain, but the collected data support the hypothesis of a link of some of these structures with the ancient nucleus of the Citadel of Erbil.

Dal 2011 La MAIKI opera nei governatorati di Erbil e Sulaimaniya, e focalizza le sue attività sulla Cittadella di Erbil e sul sito di Paikuli. Gli studi storico-archeologici sui siti sono stati affiancati da importanti attività di documentazione e gestione dei dati caratterizzate dall’'utilizzo di alcune tra le più moderne risorse a disposizione.

AIM: To investigate the effect of drinking sulphate-bicarbonate-calcium thermal water (TW) on risk factors for atherosclerosis and cholesterol gallstone disease. METHODS: Postmenopausal women with functional dyspepsia and/or constipation underwent a 12 d cycle of thermal (n = 20) or tap (n = 20) water controlled drinking. Gallbladder fasting volume at ultrasound, blood vitamin E, oxysterols (7-beta-hydroxycholesterol and 7-ketocholesterol), bile acid (BA), triglycerides, total/low density lipoprotein and high density lipoprotein cholesterol were measured at baseline and at the end of the study. Food consumption, stool frequency and body weight were recorded daily. RESULTS: Blood lipids, oxysterols and vitamin E were not affected by either thermal or tap water consumption. Fasting gallbladder volume was significantly (P < 0.005) smaller at the end of the study than at baseline in the TW (15.7 +/- 1.1 mL vs 20.1 +/- 1.7 mL) but not in the tap water group (19.0 +/- 1.4 mL vs 19.4 +/- 1.5 mL). Total serum BA concentration was significantly (P < 0.05) higher at the end of the study than at baseline in the TW (5.83 +/- 1.24 mu mol vs 4.25 +/- 1.00 mu mol) but not in the tap water group (3.41 +/- 0.46 mu mol vs 2.91 +/- 0.56 mu mol). The increased BA concentration after TW consumption was mainly accounted for by glycochenodeoxycholic acid. The number of pasta (P < 0.001), meat (P < 0.001) and vegetable (P < 0.005) portions consumed during the study and of bowel movements per day (P < 0.05) were significantly higher in the TW than in the tap water group. Body weight did not change at the end of the study as compared to baseline in both groups. CONCLUSION: Sulphate-bicarbonate-calcium water consumption has a positive effect on lithogenic risk and intestinal transit and allows maintenance of a stable body weight despite a high food intake.

Rapporto sulle attività archeologiche condotte nel 2007 dalla missione dell'Università di Bologna nella valle dello Yagnob (Tajikistan), diretta dal prof. A.C.D. Panaino.

Il volume Preservation of Cultural Heritage of the Kurdish Region in Iraq presenta i principali risultati del primo biennio (2009-2010) di lavori della Missione Archeologica Italiana nel Kurdistan iracheno, codiretta da Carlo G. Cereti e Roberta Giunta. Il progetto (Italian Cooperation Project in Iraqi Kurdistan), nato grazie all’appoggio della Direzione Generale per la Cooperazione allo Sviluppo della Repubblica Italiana, rappresenta un importante passaggio nella collaborazione, iniziata nel 2006, tra il Kurdistan Iracheno e l’IsIAO (Istituto per l’Africa e l’Oriente, Roma). Il presente volume rappresenta una prima sintesi, di grande spessore, delle ricerche ad ampio raggio intraprese dalla Missione nella capitale del Kurdistan, Erbil, e nel territorio, finalizzate alla conoscenza, al restauro e alla valorizzazione del patrimonio archeologico, storico e monumentale del Kurdistan iracheno. Riedizione digitale del volume pubblicato nell’aprile 2011 da IsIAO (Roma). The book Preservation of Cultural Heritage of the Kurdish Region in Iraq presents the main results of the first two years (2009-2010) of activity of the Italian Archaeological Mission in Iraqi Kurdistan, co-directed by Carlo G. Cereti and Roberta Giunta. The project (Italian Cooperation Project in Iraqi Kurdistan), thanks to the support of the Italian Direzione Generale per la Cooperazione allo Sviluppo, is an important step in the collaboration, begun in 2006, between Iraqi Kurdistan and IsIAO (Italian Institute for Africa and the East, Rome). This volume represents a first interim report of the wide-range researches undertaken by the Mission in the Capital of Kurdistan, Erbil, and in its territory, aimed at a better knowledge, preservation and enhancement of the archaeological, historical and monumental heritage of Iraqi Kurdistan. Digital edition of the book published in April 2011 by IsIAO (Rome).

Grounding on our former 3D QSAR studies, a knowledge-based screen of natural bile acids from diverse animal species has led to the identification of avicholic acid as a selective but weak TGRS agonist. Chemical modifications of this compound resulted in the disclosure of 6 alpha-ethyl-16-epi-avicholic acid that shows enhanced potency at TGRS and FXR receptors. The synthesis, biological appraisals, and structure-activity relationships of this series of compounds are herein described. Moreover, a thorough physicochemical characterization of 6 alpha-ethyl-16-epi-avicholic acid as compared to naturally occurring bile acids is reported and discussed.

Un accordo di collaborazione tra Sapienza e autorità iraniane ha permesso l’avvio di nuove indagini archeologiche a Estakhr (Iran - epoca sasanide e islamica). Durante la prima campagna (primavera 2012) è stata effettuata una ricognizione topografica e archeologica del sito.

The site of Barikot, after a preliminary investigation, was the subject of study by the Italian Archaeological Mission from 1978, when Giorgio Stacul began to investigate the flat area located South of the hill that gives a name to the site. The works of Stacul also brought to light important architectural remains of a large settlement of the historical period that was the subject of a successful series of excavations started in 1984. The archaeological data and the study of the historical sources have provided valuable confirmation of the identification, already proposed by A. Stein and G. Tucci, of this site with the city of Bazira remembered by Classical historians as conquered by Alexander in 327 BCE. The studies made so far have confirmed the great archaeological and historical importance of this urban site, located in a strategic position from which one can dominate the roads leading to the upper and lower valley of Swat and to Buner, and have highlighted the astonishing occupational continuity and the impressive stratigraphic sequence that make Barikot a crucial site for the understanding of the evolutional processes of the region. Despite some interruptions due to the international situation, the excavations have continued until today; ten trenches were opened on the alluvial plain at the foot of the hill or on the two artificial terraces overlooking the hill and were preceded by a complete survey of the site and of all the emerging structures.

vengono presi in esame e descritti gli aspetti epidemiologici, patogenetici, clinici e terapeutici della malattia steno-ostruttiva della carotide extraxranica

We model long range correlations of nucleotides in the human DNA sequence using the long range one dimensional Ising model. We show that for distances between $10^3$ and $10^6$ bp the correlations show an universal behaviour and may be described by the non-mean field limit of the long range 1d Ising model. This allows us to make some testable hypothesis on the nature of the interaction between distant portions of the DNA chain which led to the DNA structure that we observe today in higher eukaryotes., Comment: 15 pages, 6 figures. Substantial changes in sect. 4.2. Some clarifications and comments added throughout the paper. Journal version

The present paper deals with the development of a rapid and feasible high-performance liquid chromatographic method for the determination of trazodone and its main active metabolite 3-(1-clorophenyl)piperazine (m-CPP) in human plasma. Trazodone is a second-generation antidepressant with serotonin antagonist activity. The metabolite seems to be involved in the onset of some side effects of trazodone therapy, thus its determination is very important during therapeutic drug monitoring. Separation was achieved using a C8 reversed-phase column and a mobile phase composed of aqueous phosphate buffer (70%), containing triethylamine, at pH 3.5 and acetonitrile (30%). The UV detector was set at 255 nm and loxapine was used as the internal standard. An original pre-treatment procedure of plasma samples was developed, based on solid-phase extraction with C8 reversed phase cartridges (50 mg, 1 mL). The obtained extraction yields values were higher than 90% and precision, expressed as RSD, was lower than 5.6%. The method was successfully applied to plasma samples from depressed patients undergoing therapy with trazodone; accuracy results were satisfactory (recovery > 91%). Thus, the method seems to be suitable for the therapeutic drug monitoring of trazodone and its main active metabolite in depressed patients' plasma.

L'articolo analizza il rapporto esistente tra l'identità nazionale iraniana e il patrimonio culturale del paese e l'uso politico che spesso viene fatto di quest'ultimo.

The authors introduce new studies on the metallurgic activity carried out in the archaeological site of Barikot (Swat, Pakistan). The collaboration between the IsIAO Italian Archaeological Mission in Pakistan and the Diagnostic Laboratory of the Department of Storie e Metodi per la Conservazione dei Beni Culturali of the Alma Mater Studiorum University of Bologna allowed the achievement of new useful data that are quite interesting even if the research is still at the beginning and needs further checks. In particular some samples show traces of niobium. This element is fairly rare but, in some cases, is present into the crystal net of cassiterite. In the samples, the traces of niobium are always correlated with the presence of tin in the alloy. If these data will be confirmed, it’s going to be possible to hypothesise that tin minerals used for the alloy of the object found at Barikot may come from mining sites characterized by the presence of niobium.

Il trazodone (2-[3-[4-(3-clorofenil)-1-piperazinil]propil]-1,2,4-triazolo[4,3-a]piridin-3(2H)-one, TRZ) è stato approvato nel 1998 per il trattamento della depressione maggiore. TRZ è un debole inibitore del reuptake delle monoammine ed è un antagonista dei recettori della serotonina. Il metabolismo epatico produce il principale metabolita attivo del trazodone, l'1-(3-cloro-fenil)piperazina (mCPP), agonista serotoninergico con una lunga emivita plasmatica. I principali effetti collaterali del trattamento con TRZ sono: sedazione, ipotensione ortostatica, emicrania, capogiri e nausea. Alcuni di questi effetti collaterali (come nausea ed emicrania) sono stati attribuiti anche ad mCPP. Quindi è evidente l'importanza di effetturare il Monitoraggio Terapeutico (TDM) per la determinazione di TRZ e del suo principale metabolita mCPP. Lo scopo di questo lavoro è lo sviluppo di un metodo analitico semplice ed affidabile, basato sull'HPLC-UV, per la determinazione di questi composti in plasma umano. Una colonna a fase inversa C8 è usata come fase stazionaria ed una miscela di tampone fosfato acido (70%) ed acetonitrile (30%) come fase mobile. La rivelazione spettrofotometrica è effettuata alla lunghezza d'onda di 255 nm. Il campione di plasma (125 µL) viene sottoposto ad estrazione in fase solida (SPE) su cartucce C8 e l'eluizione viene effettuata con metanolo. La procedura SPE garantisce soddisfacenti rese d'estrazione (> 90%) ed una buona purificazione della matrice biologica. Il metodo è attualmente in fase di convalida e si è dimostrato promettente per il TDM di TRZ e mCPP in plasma di pazienti depressi.

Omeprazole (6-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazo-le, OMP) and lansoprazole (2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]sulfinyl]-1H-benzimidazole, LNP) are two of the most widely used anti-ulcer agents which act on the gastric H+-K+-ATPase pump, irreversibly inhibiting it and thus effectively reducing the acid secretion. They are used in the treatment of peptic ulcer of any origin and also for the treatment of gastro-esophageal reflux disease and as gastroprotectives during prolonged anti-inflammatory therapy cycles. OMP is administered at doses ranging from 10 to 40 mg/day, while LNP usual daily doses are in the 15-30 mg/day range. The typical therapy cycle lasts 8 weeks, but OMP and LNP are often prescribed by physicians for the occasional, acute treatment of gastric pain. However, clear dose/plasma level correlations have not been established. The main side effects are cephalea, abdominal pain, diarrhea, nausea, vomit, dry mouth, dermatitis, insomnia and rarely hepatitis, leukopenia, agitation, broncoconstriction. For these reasons, it is clear that a suitable therapeutic drug monitoring can be helpful in establishing chemical-clinical correlations leading to a safer and more effective use of these drugs. Feasible and relatively inexpensive analytical methods are obviously needed for the determination of OMP and LNP in human plasma. The methods should be capable of discriminating the two drugs: physicians often switch from OMP to LNP and vice versa, perceiving them as mostly equivalent, thus their simultaneous analysis is necessary. The aim of this study is the development of a simple and reliable HPLC method coupled to UV detection for the separation and the simultaneous determination of OMP and LNP in plasma. The developed method uses a C8 column (150×4.6 mm I.D., 5 μm) as the stationary phase and a mixture of acetonitrile and a pH 6.0 phosphate buffer containing triethylamine (30/70, v/v) as the mobile phase. UV detection is carried out at 220 nm. Indomethacin was chosen as the Internal Standard (IS). The sample pre-treatment is carried out by solid-phase extraction (SPE) using C8 cartridges; 250 µL of human plasma are sufficient for a complete analysis. The SPE procedure allows concentration of the analytes, while eliminating most endogenous and hexogenous interference. Extraction yield assays gave good results, with absolute recovery values always higher than 92%. Studies are in progress to complete the method validation.

A study on three populations of Bombina pachypus was carried out in order to improve our knowledge on the biology of this threatened species in northeastern Apennines (Romagna region). In particular the authors provide the habitat description of three reproductive sites and the population estimate of the species through Capture-Mark-Recapture method. Three sites were monitored: (a) Sommorio(RA), consisting of three ponds, fed by a spring in a broad-leaf forest; (b) Monte Castellaccio (RA), two artificial cemented basins within an open grassland;(c) Ca’ di Veroli(FC), two ponds along the basin of a hill-stream which runs on a rocky bed through a broad-leaf forest. Surveys were carried out once a month during the activity season (April-October) for three years (2004, 2005, 2006). For each individual, photographs were made to the ventral pattern and biometric parameters were taken. The three populations resulted stable through the years; sex ratio is in favour of males; the growth was faster in young males though the first years, but adult females reached a larger SVL at the end of their development. Annual changes in water level appeared to be an important factor influencing the reproductive outcome and population size.

Assente

Soymen GN is a new commercial preparation, containing soy extract and melatonin for the treatment of menopausal symptoms such as insomnia, hot flushes, tachycardia and osteoporosis. The commercial package contains two kinds of soft gelatin capsules: the “light” capsules for morning administration contain soybean extract (40 mg), while the “dark” capsules for evening administration contain soy extract (40 mg) and melatonin (5 mg). The main active compounds are the isoflavones, which are present both as aglycones and as glycosides: genistein, daidzein, glycitein, genistin and daidzin. These compounds are of particular interest for their possible estrogenic effects on the symptoms of menopause, in fact they have been used in therapy as a replacement to estrogen deficiency as a consequence of menopause. Melatonin is a hormone whose main function is the regulation of circadian rhythms. Thus, it can be helpful for the relief of insomnia and other sleep disturbances. The aim of this study is to develop a quality control system for the Soymen GN formulation. For this purpose, it is important to have access to reliable analytical methods for the determination of melatonin and of the main soy isoflavones, both aglycones and glycosides. Two original HPLC methods coupled to spectrophotometric and amperometric detection, respectively, have been developed for the quality control of Soymen GN capsules. UV detection is carried out at 260 nm, while amperometric detection is carried out at an oxidation potential of + 800 mV. The chromatographic separation is obtained using a reversed-phase C8 column as the stationary phase and a mixture of acetonitrile and an acidic phosphate buffer (30/70, v/v) as the mobile phase. A third analytical method based on micellar electrokinetic chromatography is currently undergoing validation. The BGE is composed of a 25 mM, pH 10.3 carbonate buffer, containing 55 mM SDS and 5% methanol. The analytes are quantitatively extracted from both “light” and “dark” capsules by agitation in a methanol/water mixture. From these preliminary results, all three methods seem to be promising for the quality control of the new formulation.

Lo scopo di questo studio è approfondire le conoscenze sulla biologia di popolazioni naturali di Bombina pachypus (Bonaparte, 1838) presenti in diversi ambienti (sorgenti, abbeveratoi, pozze di torrente), per meglio comprendere i fattori di minaccia che ne stanno determinando il declino e per valutare l’opportunità di eventuali azioni di conservazione.

It was on the valleys S of Bir-kot-ghwandai that Giuseppe Tucci made his seminal, fundamental observations on the ancient history and archaeology of Swat (1958). It is with a feeling of pride and satisfaction that our Mission returns on its own tracks, also because this happens – and we envisage this as a, particularly appropriate coincidence– on the celebration of our 50th year of continuous field activity. We present the first part of the preliminary report of the Archaeological Map of the Swat valley (AMSV) project, led by Luca M. Oliveri (LMO) and Massimo Vidale (MV) in the framework of the IsIAO Archeological Mission (IAM) activities directed by P. Callieri. This preliminary report has the goal to present all data so far collected during our 2000-2005 survey campaigns, concerning an area of about 100 km.

Assente

This thesis reports an integrated analytical approach for the study of physicochemical and biological properties of new synthetic bile acid (BA) analogues agonists of FXR and TGR5 receptors. Structure-activity data were compared with those previous obtained using the same experimental protocols on synthetic and natural occurring BA. The new synthetic BA analogues are classified in different groups according also to their potency as a FXR and TGR5 agonists: unconjugated and steroid modified BA and side chain modified BA including taurine or glycine conjugates and pseudo-conjugates (sulphonate and sulphate analogues). In order to investigate the relationship between structure and activity the synthetic analogues where admitted to a physicochemical characterization and to a preliminary screening for their pharmacokinetic and metabolism using a bile fistula rat model. Sensitive and accurate analytical methods have been developed for the quali-quantitative analysis of BA in biological fluids and sample used for physicochemical studies. Combined High Performance Liquid Chromatography Electrospray tandem mass spectrometry with efficient chromatographic separation of all studied BA and their metabolites have been optimized and validated. Analytical strategies for the identification of the BA and their minor metabolites have been developed. Taurine and glycine conjugates were identified in MS/MS by monitoring the specific ion transitions in multiple reaction monitoring (MRM) mode while all other metabolites (sulphate, glucuronic acid, dehydroxylated, decarboxylated or oxo) were monitored in a selected-ion reaction (SIR) mode with a negative ESI interface by the following ions. Accurate and precise data where achieved regarding the main physicochemical properties including solubility, detergency, lipophilicity and albumin binding . These studies have shown that minor structural modification greatly affect the pharmacokinetics and metabolism of the new analogues in respect to the natural BA and on turn their site of action, particularly where their receptor are located in the enterohepatic circulation.

Preliminary Report on the Autumn 2000 Campaign and archaeological excavation of the IsIAO Italian Archaeological Mission in Pakistan at Bir-kot-ghwandai, Swat, Pakistan.

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Departamento de Psiquiatría. Fecha de lectura: 16 de Marzo de 2012

Preliminary report of the 1998/1999 archaeological excavation at Barikot/Bir-kot-ghwandai, Swat, Pakistan.

La presente comunicación tiene por objeto examinar la evolución de la experiencia europea de utilización de satélites para la educación y la formación profesional a distancia, destacando el papel promotor desempeñado por las organizaciones internacionales y organismos comunitarios, reseñando brevemente los más importantes programas de la Comunidad Europea destinados al desarrollo de las nuevas modalidades de enseñanza y aprendizaje, y presentando los grandes proyectos europeos de educación a distancia por satélite.

Introducción a las redes sociales en internet.