Validación del Timed up and go test como predictor de riesgo de caídas en sujetos con artritis reumatoide. Parte I: confiabilidad y aplicabilidad clínica / Validation of the timed up and go test as a predictor of the risk of falls in persons with rheumatoid arthritis. Part I: reliability and clinical applicability

Introducción. Los sujetos con artritis reumatoide (AR) tienen un elevado riesgo de caídas. Se necesitan herramientas para determinar qué pacientes tienen mayor riesgo de caerse. El Timed up and go test (TUG) es utilizado para predecir el riesgo de caídas, pero es imprescindible que se estudien sus propiedades psicométricas. El objetivo es establecer la confiabilidad intra e interobservador, test-retest y aplicabilidad clínica del TUG a la velocidad habitual y máxima-segura en sujetos con diagnóstico de AR. Material y método. Estudio observacional, prospectivo y longitudinal. Se estableció la confiabilidad intra e interobservador y test-retest del TUG con el coeficiente de correlación intraclase. Se construyeron gráficos de Bland-Altman para la concordancia intra e interobservador. Resultados. La confiabilidad intraobservador fue CCI 0,98 (IC 95%: 0,96-0,99) y CCI 0,99 (IC 95%: 0,98-0,99) a velocidad habitual y máxima CCI 0,97 (IC 95%: 0,95-0,98) y CCI 0,99 (IC 95%: 0,99-0,99). La confiabilidad interobservador a velocidad habitual obtuvo CCI 0,99 (IC 95% 0,98-0,99) y a velocidad máxima CCI 0,99 (IC 95% 0,99-0,99). La confiabilidad test-retest a velocidad habitual CCI 0,77 (IC 95%: 0,61-0,87) y a máxima CCI 0,91 (IC 95%: 0,83-0,95). El 23% reportó mínima dificultad para comprender el test. La mediana del tiempo de administración fue 90 segundos. Conclusión. El estudio permitió establecer la confiabilidad intra e interobservador, test-retest y aplicabilidad clínica del TUG test a velocidad habitual y máxima segura en sujetos con AR (AU)

Introduction. Persons with rheumatoid arthritis (RA) have a high risk of falls. There is a need for tools that identify at-risk patients. The Timed Up and Go test (TUG) is used to predict the risk of falls but it is essential to study its psychometric properties. The aim of this study was to establish intra- and interobserver reliability, test-retest reliability and the clinical applicability of the TUG test in persons with a diagnosis of RA. Material and method. Observational, prospective, longitudinal study. intra- and interobserver reliability and the test-retest reliability of the TUG were established with intraclass correlation coefficients (ICC). Bland-Altman plots were constructed for intra- and interobserver reliability. Results. The intraobserver reliability ICC for the two assessors was 0.98 (95% CI 0.96-0.99) and 0.99 (95% CI 0.98-0.99), and was 0.97 (95% CI 0.95-0.98) at normal speed and 0.99 (95% CI 0.99-0.99) at maximal speed. The interobserver reliability ICC at normal speed was 0.99 (95% CI 0.98-0.99) and 0.99 (95% CI 0.99-0.99) at maximal speed. The test-retest reliability ICC was 0.77 (95% CI 0.61-0.87) at normal speed and 0.91 (95% CI 0.83-0.95) at maximal speed. A total of 23% of the participants reported minimal difficulty in understanding the test. The average administration time was 90seconds. Conclusion. This study identifies the intra- and interobserver reliability, test-retest reliability and the clinical applicability of the TUG test at normal and maximal speed in RA patients (AU)

A Rare Cause of Abdominal Pain.

CASE: A 54 year old woman with hypothyroidism presented with right flank pain that began acutely one week prior to presentation. She was told initially she had a urinary tract infection and treatment resulted in mild symptomatic improvement. The pain returned and she presented to another Emergency Department (ED); and was told the pain was due to constipation. She returned to the ED the next day when her pain worsened and her labs were notable for WBC of 19,000/uL, BUN/Cr of 28/0.75 mg/dL, AST of 31 U/L, ALT of 92 U/L and total bilirubin of 0.6 mg/dL. RUQ ultrasound was notable for dilation of the common bile duct. Given concern for choledocholithiasis, she was started on cefepime and metronidazole. MRCP demonstrated a distended gallbladder without stones and a small amount of pericholecystic fluid. Also noted were two areas of increased signal in the right kidney, concerning for neoplasia or infarction. Contrasted abdominal Computed tomography showed a moderate size area of hypodensity, consistent with renal infarct. Workup for embolic source of the infarction was unrevealing. Renal artery angiogram demonstrated a spontaneous dissection of the superior branch of the right renal artery. PCI was not performed due to risk of jeopardizing the other vessels and so she was managed medically with rivaroxaban along with hydrochlorothiazide and metoprolol succinate to keep her systolic blood pressure below 140 mmHg. The morning after the procedure, the patient told the treatment team that her grandson liked to jump from a height and she would catch him on her right side. This was felt to be a likely etiology of her spontaneous dissection. At the time of discharge, her pain was improved and repeat angiogram performed eight weeks later noted healing of the dissection. DISCUSSION: Spontaneous renal artery dissection is a rare cause of abdominal pain and often presents a diagnostic and therapeutic challenge. This case highlights the importance of considering alternate etiologies of localized abdominal pain when other common pathologies have been excluded.

[Hand fine motor skills and use of both hand and arm in subjects after a stroke: a systematic review]. / Herramientas de evaluacion del uso fino de la mano y uso de la mano y el brazo en sujetos con secuela de ictus: revision sistematica.

INTRODUCTION: In clinical practice it is important to be able to assess the function of the upper limb of the patient who has suffered a stroke. There is currently no systemic review that could identify assessment tools for the 'fine use of the hand' and 'use of both hand and arm'. AIMS: Primary, to identify observational tools which can assess the fine use of the hand and the use of both hand and arm in patients with stroke sequels. Secondary, to analyze the bias risk in the included articles, describing and categorizing the clinical utility, validity and reliability. PATIENTS AND METHODS: A search was carried in Medline, LILACS, SciELO and Open Grey, which included articles published until October 2015. Studies that validate assessing tools of the upper limb in subjects with a stroke sequel which evaluate the fine use of the hand and the use of both hand and arm were included. RESULTS: Eleven tools in evaluate observational haven been selected, which assess the fine use of the hand and the use of hand and arm. CONCLUSIONS: In every case both validity and reliability have been reported, but clinical utility has been less considered for assessment. The studies that researched these tools showed a high risk of bias in their development. ARAT-19 showed a lower bias risk, but when it has to do with applicability and the reference trial is taken into account, the level of concern is high.

TITLE: Herramientas de evaluacion del uso fino de la mano y uso de la mano y el brazo en sujetos con secuela de ictus: revision sistematica.Introduccion. En la practica clinica resulta importante poder evaluar la funcion de la extremidad superior paretica del paciente que ha sufrido un ictus. No hay una revision sistematica que identifique herramientas de evaluacion del 'uso fino de la mano' o el 'uso de la mano y el brazo'. Objetivos. Como objetivo primario, identificar las herramientas observacionales que evaluan el uso fino de la mano o el uso de la mano y el brazo en pacientes con secuela de ictus. Secundariamente, analizar el riesgo de sesgo de los articulos incluidos, describir y categorizar la validez, fiabilidad y utilidad clinica. Pacientes y metodos. Se realizo una busqueda en Medline, LILACS, SciELO y Open Grey hasta octubre de 2015. Se incluyeron estudios de validacion de herramientas de evaluacion del miembro superior en sujetos con secuela de ictus, que evaluen el uso fino de la mano o el uso de la mano y el brazo. Resultados. Se han seleccionado 11 herramientas que evaluan el uso fino de la mano y el uso de la mano y el brazo. Conclusiones. Si bien se comunicaron la fiabilidad, la validez y la utilidad clinica, esta ultima fue menos evaluada. Los estudios que investigaron estas herramientas presentaron alto riesgo de sesgo, en particular en la eleccion de la prueba de referencia. La herramienta ARAT-19 fue la que presento un menor riesgo de sesgo, pero cuando se evaluo la aplicabilidad, esta presento una preocupacion alta para la prueba de referencia.

[Peripheral nerve stimulation effectiveness in the upper limb function recovery of patients with a stroke sequel: systematic review and meta-analysis]. / Efectividad de la estimulacion nerviosa periferica en la recuperacion de la funcion del miembro superior en sujetos con secuela de ictus: revision sistematica y metaanalisis.

INTRODUCTION: In 30-66% of the cases, people who survive a stroke suffer from an affected non functional upper limb. Somatosensory stimulation might positively influence the muscular activity of patients with motor deficiencies caused by a stroke. AIM: To carry out a systematic review and a meta-analysis of the effectiveness of peripheral nerve stimulation (PNS) use in the improvement of the plegic/paretic upper limb function in patients with a stroke sequel. SUBJECTS AND METHODS: Randomized and non randomized clinically controlled tests and crossover studies published until November 2014 in Medline electronic database, Cochrane Central Register of Controlled Trials, LILACS, SciELO and Open Grey were included. Studies at high risk of bias were excluded. Two independent researchers assessed the studies' eligibility criteria and retrieved and analyzed all data. RESULTS: A total of 1,967 studies were found, five of them were included for data retrieval and analysis, using a risk of bias fashion of 6/10 at the PEDro scale. 224 patients were included, 95 of them received PNS in multiple modalities and 129 received other interventions as a control group. CONCLUSION: The analyzed data suggest that the function of the plegic/paretic upper limb improves after the application of PNS either with or without functional training. On the other hand, the meta-analysis result indicates that there is still insufficient evidence to guarantee the effectiveness of PNS use for the recovery of the plegic/paretic upper limb function in patients with a stroke sequel.

TITLE: Efectividad de la estimulacion nerviosa periferica en la recuperacion de la funcion del miembro superior en sujetos con secuela de ictus: revision sistematica y metaanalisis.Introduccion. Un 30-66% de las personas que sobreviven a un ictus queda con un miembro superior afectado. La estimulacion nerviosa periferica (ENP) influiria positivamente en la actividad muscular de pacientes con deficits motores secundarios a un ictus. Objetivo. Realizar una revision sistematica y un metaanalisis acerca de la efectividad de la aplicacion de la ENP en la recuperacion de la funcion del miembro superior plejico/paretico en sujetos con secuela de ictus. Sujetos y metodos. Se incluyeron ensayos clinicos controlados aleatorizados y no aleatorizados, y estudios cruzados, publicados hasta noviembre de 2014 en Medline, Cochrane Central Register of Controlled Trials, LILACS, SciELO y Open Grey. Se excluyeron articulos con alto riesgo de sesgo. Dos investigadores independientes evaluaron la elegibilidad de los estudios, y realizaron la extraccion y analisis de los datos. Resultados. Se encontraron 1.967 articulos, de los cuales se incluyeron cinco para la extraccion de datos y analisis, con una moda de riesgo de sesgo de 6/10 en la escala PEDro. Se incluyeron en total 224 sujetos, de los cuales 95 recibieron ENP en diversas modalidades y 129 recibieron otras intervenciones como grupo control. Conclusion. Los datos analizados sugieren que la funcion del miembro superior plejico/paretico mejora tras la aplicacion de ENP en conjunto o no con entrenamiento funcional. Sin embargo, el resultado del metaanalisis indica que aun no se dispone de evidencia suficiente para avalar la efectividad del uso de ENP para la recuperacion de la funcion del miembro superior plejico/paretico en sujetos con secuela de ictus.

ICF-based approach to evaluating functionality in cardiac rehabilitation patients after heart surgery.

BACKGROUND: Heart surgery is a frequent reason for admission to in-patient cardiac rehabilitation programmes. ICF approach has never been used to evaluate cardiac patients after major heart surgery. AIM: The aim was to evaluate and measure functionality in cardiac patients who have undergone heart surgery, using for the first time the ICF-based approach and to assess whether such approach can be feasible and useful in cardiac rehabilitation. DESIGN: Observational study. SETTING: In-patients cardiac Rehabilitation Unit in Milan. POPULATION: Fifty consecutively admitted patients who had undergone heart surgery (34 males, 16 females; mean age 65.7±12.5 years). METHODS: We prepared a ICF-core set short enough to be feasible and practical. Patients were individually interviewed by different healthcare professionals (randomly selected from a group of two physicians, two physiotherapists and two psychologists) at the beginning (T1) and end of cardiac rehabilitation (T2) RESULTS: The sum of the scores of each ICF body function, body structure, activity and participation code significantly decreased between T1 and T2 (P<0.001). The environmental code scores significantly decreased in the case of facilitators between T1 and T2 (P=0.0051), but not in the case of barriers. There were significant correlations between the ICF body function scores and Barthel's index (ρ=0.381; P=0.006), NYHA class (ρ=0.404; P=0.004) and plasma Cr-P levels (r=0.31; P=0.03), between the ICF body structure codes and the Conley scale (ρ=0.306; P=0.02), and between the activity/participation codes and SpO2 (ρ=0.319; P=0.04). There were no correlations between the ICF environmental codes and clinical parameters. CONCLUSION: The ICF-based data provided functional information that was consistent with the patients' clinical course. CLINICAL REHABILITATION IMPACT: The core set used allowed to quantify important body functions and activities, including some areas that are generally insufficiently considered by healthcare professionals during cardiac rehabilitation, and document their improvement.

NIR luminescence for the inspection of thermal paper: a novel tool for fingermarks detection.

The near infrared (NIR) spectral region could offer advantages over the visible region in the detection of latent fingermarks due to the enhanced contrast between the background and the print. In this present paper, this spectral range of the electromagnetic spectrum was explored in order to study the possibility to make feasible the inspection of forensic evidences when the substrate is represented by the thermal paper, which is one of the most extensively used porous surfaces for printing receipts. We successfully applied the method to thermal paper treated with several kinds of amino acid sensitive reagents. We demonstrated that, even if the treatments could cause a dark stain over the latent fingermarks, by exploiting the luminescence of thermal paper in the NIR window we were able to create a contrast otherwise impossible in the visible region.

A focus on heme oxygenase-1 (HO-1) inhibitors.

The aim of this review is to highlight the advances in the field of heme oxygenase-1 (HO-1) inhibitors over the past years, particularly from a medicinal chemistry point of view; progresses made in the field strongly helped to clarify physiological roles of the heme oxygenase (HO) system. HO is a family of ubiquitously expressed enzymes which regulate the regiospecific catabolism of heme leading to the formation of equimolar amounts of carbon monoxide (CO), ferrous iron (Fe⁺⁺), and biliverdin. HO exists in two distinct, catalytically active isoforms: HO-1 and HO-2. HO-1 is an inducible 32-kDa protein, while HO-2 is a constitutively synthesized 36-kDa protein and generally is unresponsive to any of the inducers of HO-1. A third isoform, HO-3, is still an elusive protein. The HO system, along with its catabolism products, is involved in a variety of crucial physiological functions, including cytoprotection, inflammation, anti-oxidative effects, apoptosis, neuro-modulation, immune-modulation, angiogenesis, and vascular regulation. The use of selective HO inhibitors is a very important tool to clarify the role of the HO system and the mechanisms underlying its physiological effects and pathological involvement; due to the inducible nature of HO-1, selective inhibition of HO-1 isoform is generally preferable. Notably, HO-1 inhibitors may be also beneficial in therapeutic applications and have been mainly studied for treatment of hyperbilirubinemia and certain types of cancer. Historically, the first molecules used as non selective HO-1 inhibitors were metalloporphyrins (Mps). The subsequent development of the imidazole-dioxolane derivatives afforded the first generation of non-porphyrin based, isozyme selective HO-1 inhibitors.

Large-scale species delimitation method for hyperdiverse groups.

Accelerating the description of biodiversity is a major challenge as extinction rates increase. Integrative taxonomy combining molecular, morphological, ecological and geographical data is seen as the best route to reliably identify species. Classic molluscan taxonomic methodology proposes primary species hypotheses (PSHs) based on shell morphology. However, in hyperdiverse groups, such as the molluscan family Turridae, where most of the species remain unknown and for which homoplasy and plasticity of morphological characters is common, shell-based PSHs can be arduous. A four-pronged approach was employed to generate robust species hypotheses of a 1000 specimen South-West Pacific Turridae data set in which: (i) analysis of COI DNA Barcode gene is coupled with (ii) species delimitation tools GMYC (General Mixed Yule Coalescence Method) and ABGD (Automatic Barcode Gap Discovery) to propose PSHs that are then (iii) visualized using Klee diagrams and (iv) evaluated with additional evidence, such as nuclear gene rRNA 28S, morphological characters, geographical and bathymetrical distribution to determine conclusive secondary species hypotheses (SSHs). The integrative taxonomy approach applied identified 87 Turridae species, more than doubling the amount previously known in the Gemmula genus. In contrast to a predominantly shell-based morphological approach, which over the last 30 years proposed only 13 new species names for the Turridae genus Gemmula, the integrative approach described here identified 27 novel species hypotheses not linked to available species names in the literature. The formalized strategy applied here outlines an effective and reproducible protocol for large-scale species delimitation of hyperdiverse groups.

Macroevolution of venom apparatus innovations in auger snails (Gastropoda; Conoidea; Terebridae).

The Terebridae are a diverse family of tropical and subtropical marine gastropods that use a complex and modular venom apparatus to produce toxins that capture polychaete and enteropneust preys. The complexity of the terebrid venom apparatus suggests that venom apparatus development in the Terebridae could be linked to the diversification of the group and can be analyzed within a molecular phylogenetic scaffold to better understand terebrid evolution. Presented here is a molecular phylogeny of 89 terebrid species belonging to 12 of the 15 currently accepted genera, based on Bayesian inference and Maximum Likelihood analyses of amplicons of 3 mitochondrial (COI, 16S and 12S) and one nuclear (28S) genes. The evolution of the anatomy of the terebrid venom apparatus was assessed by mapping traits of six related characters: proboscis, venom gland, odontophore, accessory proboscis structure, radula, and salivary glands. A novel result concerning terebrid phylogeny was the discovery of a previously unrecognized lineage, which includes species of Euterebra and Duplicaria. The non-monophyly of most terebrid genera analyzed indicates that the current genus-level classification of the group is plagued with homoplasy and requires further taxonomic investigations. Foregut anatomy in the family Terebridae reveals an inordinate diversity of features that covers the range of variability within the entire superfamily Conoidea, and that hypodermic radulae have likely evolved independently on at least three occasions. These findings illustrate that terebrid venom apparatus evolution is not perfunctory, and involves independent and numerous changes of central features in the foregut anatomy. The multiple emergence of hypodermic marginal radular teeth in terebrids are presumably associated with variable functionalities, suggesting that terebrids have adapted to dietary changes that may have resulted from predator-prey relationships. The anatomical and phylogenetic results presented serve as a starting point to advance investigations about the role of predator-prey interactions in the diversification of the Terebridae and the impact on their peptide toxins, which are promising bioactive compounds for biomedical research and therapeutic drug development.

Serotonin 5-HT3 and 5-HT4 ligands: an update of medicinal chemistry research in the last few years.

The biogenic amine serotonin (5-hydroxytryptamine, 5-HT) is one of the most studied neurotransmitters in the central nervous system. It acts through the activation of at least fourteen 5-HT receptor subtypes. Over the last two decades, high attention was devoted to the 5-HT(3) and 5-HT(4) receptors due to their colocalization in the gastrointestinal tract and because their ligands are useful in the treatment of intestinal serotonergic system dysfunctions. The focus of this review is to discuss the literature concerning recent advances on 5-HT(3)R and 5-HT(4)R ligands and their structure-activity relationships from a medicinal chemistry perspective. During the last few years, new and significant progresses have been made in the field of novel potent and selective ligands, mixed ligands, agonists, partial agonists, and antagonists, and a number of patents have been filed. Furthermore several ligands targeting the 5-HT(3)R and 5-HT(4)R have been proposed for novel therapeutic indications such as the treatment of various psychiatric disorders.

Synthesis of 1,2,4-triazole derivatives: binding properties on endothelin receptors.

In the present study we describe the synthesis of a new series of 1,2,4-triazoles: [3-(arylmethyl)thio-5-aryl-4H-[1,2,4]triazol-4-yl]acetic acids 5a-g, [5-(arylmethyl)thio-3-aryl-1H-[1,2,4]triazol-1-yl]acetic acids 8a-d, and [3-(aryl-methyl)thio-5-aryl-1H-[1,2,4]triazol-1-yl] acetic acids 9a-d. These compounds were tested in binding assays to evaluate their ability as ligands for human ET(A) and ET(B) receptors stably expressed in CHO cells; some of the tested compounds showed affinity in the micromolar range.

[The formation and the information of the prevention and safety in construction]. / La formazione e l'informazione sulla prevenzione e la sicurezza in edilizia.

The relation takes in consideration puts into effect it them adequacy of the information, the formation and of the training in building. It distinguishes between information, formation and training obbligatori and opportune. It indicates the necessity that the contents of the information and the formation they are: specific, punctual and it adapts to you; adaptable to the various situations, acceptable, effectively feasible; with you specify objects to you to catch up; sostenibili in terms of cost. And above all that they work for objects to it to you that us had been placed. The relation indicates which strategies an employer can follow in order to catch up adequate and a reasonable one level of informazione/formazione and which it is, today, the situation of our enterprises buildings, analyzing like the evolution of the labor market and the use of sub the contracts goes, in consisting way, to modify the situation pre-esistente. It analyzes many of the situations industrial accident researches for which the information, the formation and the training they introduce unsatisfactory. It tries to give answers to following interrogated to you opened: Which duration and which contents must have theformation? To who it goes turned? Who must be supplied? To such aim it distinguishes between: course very defined (from specific norms) for contained and duration, Iter you drained to us, course rendered obbligatori or opportune from the enforced norms, but does not codify to you. It characterizes in the employers of the small enterprises, in the attache's it specializes to you and generic and in the futures professionals of field during the scholastic formation the subjects give to privilege in the formation. It reconstructs the offer of formation, information and information available today and which addresses they can be develops to you.

Design, synthesis and binding properties of novel and selective 5-HT3 and 5-HT4 receptor ligands.

This work reports the synthesis and the binding tests on the 5-HT3 and 5-HT4 receptors of new thienopyrimidopiperazine and piperazinylacylaminodimethylthiophene derivatives, in order to identify potent and selective ligands for each receptor. The 3-amino-2-(4-benzyl-1-piperazinyl)-5,6-dimethyl-thieno[2,3-d]pyrimidin-4(3H)-one derivative 28 showed the highest affinity and selectivity for the 5-HT3 over the 5-HT4 receptor (5-HT3 Ki=3.92 nM, 5-HT4 not active), whereas the 2-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butanoylamino]-4,5-dimethyl-3-thiophenecarboxylic acid ethyl ester (41) showed the highest affinity and selectivity for the 5-HT4 over the 5-HT3 receptor (5-HT4 Ki=81.3 nM, 5-HT3 not active). Conformational analyses were carried out on the compounds of the piperazinylacylaminodimethylthiophene series (39-42) taking compound 41 as the template.

Synthesis and pharmacological screening of 1,3,4-thiadiazino[2,3-b]quinazoline derivatives.

Derivatives of 1,3,4-thiadiazino[2,3-b]quinazoline 7, 9, 9a, 12, 12a, and 13 were prepared from the 3-amino-6-bromo-2,3-dihydro-2-thioxo-4-(1H)-quinazolinone (2) and its analogue without bromine. A series of the title derivatives with or without bromine was tested and the results of pharmacological screening are discussed.

High affinity and selectivity of [[(arylpiperazinyl)alkyl]thio]thieno[2,3-d]pyrimidinone derivatives for the 5-HT(1A) receptor. Synthesis and structure-affinity relationships.

In this work we report the affinity of new thienopyrimidinones for 5-HT(1A)Rs and the selectivity versus alpha(1)ARs. The 3-amino-2-[[3-[4-(2-methoxyphenyl)-1-piperazinyl]propyl]thio]-6-ethyl -thieno[2,3-d]pyrimidin-4(3H)-one 27 is the most potent and selective (Ki 0.19 nM, selectivity 115). Compound 31 with the N4 piperazine orthonitrophenyl nucleus instead of the orthomethoxyphenyl also shows a good affinity and selectivity (Ki 1. 46 nM, selectivity 84). The results of derivatives 28, 29 and 30 (Ki 3.28, 12.59 and 4.38 nM; selectivity 24, 4 and 5, respectively), which have, respectively, an ethyl, an allyl and an acetylamino group instead of an N3 amino group, indicate the importance of this last group for the interaction with 5-HT(1A)R. Comparison of the results for the superior homologue 53 (Ki 3.72 nM, selectivity 51) and the inferior homologue 52 (5-HT(1A) Ki 1499 nM, alpha(1)A Ki NA) of 2-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-6,7-dimethyl-8H-[1, 3,4]thiadiazolo[3,2-a]thieno[2,3-d]pyrimidin-8-one 57 (Ki 23 nM, selectivity 5) shows how important the length of the chain binding the two heterocyclic systems is in the interaction with 5-HT(1A)Rs and alpha(1)ARs.

Synthesis of new [1,3,4]thiadiazolo[3,2-a]thieno[2,3-d]pyrimidinone derivatives with antiinflammatory activity.

New thiadiazolothienopyrimidinones were synthesized in continuation of efforts to prepare thienopyrimidine derivatives with analgesic and antiinflammatory activities. In this study, the effect of various substituents in the thiophene ring on the pharmacological activity of the compounds was investigated.

High potent and selective arylpiperazine derivatives as ligands for the 5-HT1A receptor.

This paper reports the synthesis and affinities on the 5-HT1A versus the alpha1A receptors of new arylpiperazinylalkylthiothienopyrimidine and thiadiazole derivatives 16-24. Arylpiperazines 16-23 show affinities values in the nanomolar range for the 5-HT1A receptor. The compound 16 is highly potent (Ki 0.26 nM, selectivity 28), the derivatives 20 and 21 are less potent, but highly selective (Ki 9.40 and 5.06 nM, selectivity 207 and 73, respectively).

Design, synthesis and binding properties of novel and selective 5-HT(3) and 5-HT(4) receptor ligands.

This work reports the synthesis and the binding tests on the 5-HT(3) and 5-HT(4) receptors of new thienopyrimidopiperazine and piperazinylacylaminodimethylthiophene derivatives, in order to identify potent and selective ligands for each receptor. The compound with higher affinity and selectivity for the 5-HT(3) over the 5-HT(4) receptor was the 3-amino-2-(4-benzyl-1-piperazinyl)-5,6-dimethyl-thieno[2,3-d]pyrimidin-4(3H)-one 28 (5-HT(3) K(i)=3.92 nM, 5-HT(4) not active), the compound with higher affinity and selectivity for the 5-HT(4) over the 5-HT(3) receptor was the 2-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butanoylamino]-4,5-dimethyl-3-thiophenecarboxylic acid ethyl ester 41 (5-HT(4) K(i)=81.3 nM, 5-HT(3) not active). Conformational analyses were carried out on the compounds of the piperazinylacylaminodimethylthiophene series (39-42) taking compound 41 as the template.