Varicella zoster immunity loss in multiple sclerosis patient treated with ocrelizumab.

Ocrelizumab is a novel humanized anti-CD20 antibody used for treatment of relapsing remitting and primary progressive multiple sclerosis with evidence of inflammatory activity. Guidelines suggest assessing vaccination status and eventually vaccinate patients with multiple sclerosis before new disease modifying therapy initiation. However, there are not any specific recommendations about vaccinal immunity reassessment after ocrelizumab injection. We describe the case of a patient who loss varicella zoster vaccinal immunity after the first ocrelizumab infusion. It is advisable to reassess vaccinal immunity to isolate non-immune patients and to adopt suitable preventive measures, including close contacts vaccination and avoidance of contacts with active infection.

Age-related miRNome landscape of cumulus oophorus cells during controlled ovarian stimulation protocols in IVF cycles.

STUDY QUESTION: Is the microRNA (miRNA) expression pattern of cumulus oophorus cells (COCs) in women undergoing medically assisted reproduction (MAR) procedures differentially modulated according to patient age and gonadotropin treatment strategy? SUMMARY ANSWER: Maternal age is an independent factor impacting miRNA expression in COCs while gonadotropin treatment may affect follicular miRNA expression and IVF efficacy. WHAT IS KNOWN ALREADY: Epigenetic mechanisms in female infertility are complex and poorly studied. DNA methylation, histone modifications, miRNAs and nucleosome positioning influence cellular machinery through positive and negative feedback mechanisms either alone or interactively. miRNAs are important regulators during oogenesis, spermatogenesis and early embryogenesis, and are reported to play a role in regulating crosstalk between the oocyte and COCs. Although miRNome analysis has been performed in female human reproductive tissues (endometrium, myometrium, cervix and ovaries), epigenetic modifications in women with infertility have not been explored in detail. In addition, the impact of gonadotropin treatments during MAR on miRNA expression in COCs has not been fully investigated. STUDY DESIGN, SIZE, DURATION: This study was carried out in 53 COC samples obtained from mature metaphase II (MII) oocytes in 53 women undergoing MAR treatment. A total of 38 samples for assay development were pooled by maternal age and gonadotropin treatment into four predetermined subgroups: ≥36 years and recombinant human FSH (r-hFSH), n = 10; ≥36 years and r-hFSH+ recombinant human-luteinizing hormone (r-hLH), n = 10; ≤35 years and r-hFSH, n = 9; ≤35 years and r-hFSH+r-hLH, n = 9. miRNome profiles were determined and compared between subgroups. Expression of defined miRNAs was validated in the remaining fifteen samples, representative of each subgroup, by quantitative polymerase chain reaction (PCR). PARTICIPANTS/MATERIALS, SETTING, METHODS: COCs were processed for miRNA-enriched total RNA extraction and pooled in homogeneous subgroups to obtain a sufficient amount and quality of starting material to perform the analysis. Each pooled sample underwent miRNA profiling using PCR assay system to examine expression of 752 human miRNAs without pre-amplification. Data were analyzed using the delta-delta Ct method for relative quantitation and prediction of target genes (with at least four algorithms predicting the same miRNA-gene interaction pair (HIT)>4). The miRSystem database provided functional annotation enrichment (raw P-value <0.05) of co-expressed miRNAs. MAIN RESULTS AND THE ROLE OF CHANCE: We found distinctive miRNA expression profiles in each subgroup correlating with age and MAR stimulation. In addition, a number of selective and co-expressed miRNAs were revealed by comparative analysis. A cluster of 37 miRNAs were commonly but differentially expressed in all four pools. Significant differences were observed in expression regulation of 37 miRNAs between age groups (≤35 or ≥36) in women receiving r-hFSH+r-hLH compared to those receiving r-hFSH alone. Higher concentrations and increased numbers of miRNAs were recorded in younger than in older patients, regardless of treatment. Functional and expression studies performed to retrieve common miRNome profiles revealed an enrichment of biological functions in oocyte growth and maturation, embryo development, steroidogenesis, ovarian hyperstimulation, apoptosis and cell survival, glucagon and lipid metabolism, and cell trafficking. The highest scored pathways of target genes of the 37 common miRNAs were associated with mitogen-activated protein kinase (MAPK) signaling pathways, G alpha signaling, transcription regulation, tight junctions, RNA polymerase I and III, and mitochondrial transcription. We identified a potential age- and MAR stimulation-dependent signature in the miRNA landscape of COCs. LIMITATIONS, REASONS FOR CAUTION: We cannot rule out the possibility that other unknown individual genetic or clinical factors may have interfered with the reported results. Since miRNA profiling was conducted with a predefined array of target probes, other miRNA molecules, potentially modulated by age and hormonal stimulation, may have been missed in this study. WIDER IMPLICATIONS OF THE FINDINGS: miRNA expression in COCs is modulated by gonadotropin treatment and correlates strongly with age. A better understanding of the expression patterns and functions of miRNAs may lead to the development of novel therapeutics to treat ovarian dysfunction and improve fertility in older women. STUDY FUNDING/COMPETING INTEREST: This study was funded by Merck KGaA, Darmstadt, Germany. All authors declared no competing interest, except SL and TD who are fully employed by Merck KGaA. TRIAL REGISTRATION NUMBER: N/A.

A Large Follicular Dentigerous Cyst: A New Multi-portal Access: Intraoral and Endoscopic Technique.

Background: The standard treatment for a dentigerous cyst of maxilla is a surgical enucleation, the extraction of the tooth. In the case of cysts involving the maxillary sinus, a Caldwell-Luc approach is used. In case of large cysts, its marsupialization is carried out in order to reduce the bone defect, followed by enucleation and extraction of the tooth. Methods: This is a case of a large follicular dentigerous cyst of upper jaw with 18 ectopic tooth within the maxillary sinus, treated in our Unit. Results: We decided to perform a multi-portal access, the intraoral endoscopic-assisted technique; an intraoral approach has been performed, but less demolishing than the routine intraoral approach, through the anterior wall of the maxillary sinus, already eroded by the lesion. The lesion was very large, occupying the entire maxillary cavity. For this reason, by means of the intraoral approach alone, it was extremely difficult to remove the lesion in its entirety. The endoscopic-assisted technique was combined with intraoral approach. The lesion extended to the maxillary ostium. This did not allow to reach the ostium through the classic endoscopic approach. Endonasal endoscopic access was used both to enucleate the cyst, that was adherent to the orbital floor and soft tissues of the OMC (osteomeatal complex), and to restore the physiological drainage of the maxillary sinus. Conclusions: We decided to perform a combined intraoral and endoscopic approach to allow a complete excision of the cystic lesion, without being very demolishing and taking advantage of the bone erosion already caused by the large cyst.

Italian study on buckwheat allergy: prevalence and clinical features of buckwheat-sensitized patients in Italy.

Buckwheat allergy is considered a rare food allergy outside of Asia. In Europe, buckwheat has been described mainly as a hidden allergen. Data on the prevalence of buckwheat hypersensitivity in non-Asian countries is very poor. The aim of this multicenter study was to evaluate the prevalence of buckwheat sensitization and its association with other sensitizations among patients referred to allergy clinics in different geographic areas of Italy. All patients referred to 18 Italian allergy clinics from February through April 2011 were included in the study and evaluated for sensitization to buckwheat and other allergens depending on their clinical history. A total of 1,954 patients were included in the study and 61.3 percent of them were atopic. Mean prevalence of buckwheat sensitization was 3.6 percent with significant difference between Northern (4.5 percent), Central (2.2 percent) and Southern (2.8 percent) regions. This is, to our knowledge, the largest epidemiological survey on buckwheat allergy reported outside of Asia. Buckwheat is an emerging allergen in Italy, being more frequently associated to sensitization in Northern regions.

Assessment of chronic wounds by three-dimensional optical imaging based on integrating geometrical, chromatic, and thermal data.

Chronic wounds represent a particular debilitating health care problem, mainly affecting elderly people. A full and correct diagnosis of tissue damage should be carried out considering both dimensional, chromatic, and thermal parameters. A great variety of methods have been proposed with the aim of producing objective assessment of skin lesions, but none of the existing technologies seem to be robust enough to work for all ulcer typologies. This paper describes an innovative and non-invasive system that allows the automatic measurement of non-healing chronic wounds. The methodology involves the integration of a three-dimensional (3D) optical scanner, based on a structured light approach, with a thermal imager. The system enables the acquisition of geometrical data, which are directly related to chromatic and temperature patterns through a mapping procedure. Damaged skin areas are detected by combining visible and thermal imaging. This approach allows for the automatic measurement of extension and depth of ulcers, even in the absence of significant and well-defined chromatic patterns. The proposed technology has been tested in the measurement of ulcers on human legs. Clinical tests have demonstrated the effectiveness of this methodology in supporting medical experts for the assessment of chronic wounds.

LABEC, the INFN ion beam laboratory of nuclear techniques for environment and cultural heritage.

The LABEC laboratory, the INFN ion beam laboratory of nuclear techniques for environment and cultural heritage, located in the Scientific and Technological Campus of the University of Florence in Sesto Fiorentino, started its operational activities in 2004, after INFN decided in 2001 to provide our applied nuclear physics group with a large laboratory dedicated to applications of accelerator-related analytical techniques, based on a new 3 MV Tandetron accelerator. The new accelerator greatly improved the performance of existing Ion Beam Analysis (IBA) applications (for which we were using since the 1980s an old single-ended Van de Graaff accelerator) and in addition allowed to start a novel activity of Accelerator Mass Spectrometry (AMS), in particular for 14C dating. Switching between IBA and AMS operation became very easy and fast, which allowed us high flexibility in programming the activities, mainly focused on studies of cultural heritage and atmospheric aerosol composition, but including also applications to biology, geology, material science and forensics, ion implantation, tests of radiation damage to components, detector performance tests and low-energy nuclear physics. This paper describes the facilities presently available in the LABEC laboratory, their technical features and some success stories of recent applications.

The use of three-dimensional reconstructions of CT scans to evaluate anomalies of hyoid bone in Pierre Robin sequence: A retrospective study.

AIM: The aim of the study was to investigate hyoid bone anomalies in patients with Pierre Robin sequence (PRS) compared to the control group, using computed tomography (CT) examination and three-dimensional reconstruction of the hyoid bone and mandible. METHODS: A retrospective study was performed of patients between birth and 12 months old with isolated PRS (i-PRS) and syndromic PRS (ni-PRS), who had undergone CT examination, and whose results were compared to the control group of the same age. DICOM data was processed to highlight bone tissue. The mandible and hyoid bones were the main targets of the three-dimensional reconstruction. The study outcomes were the analysis of hyoid bone ossification, volume, and position (distance between hyoid and mandibular symphysis). Univariate and multivariate statistical analyses were performed with α=0.05 as level of significance. RESULTS: The study sample included 29 i-PRS and 21 ni-PRS patients, while 43 infants in the control group. Hyoid ossification was present in 26/50 (52%) PRS patients (14 i-PRS; 12 ni-PRS) but in 31/43 controls (72%). Statistical analysis showed that absence of hyoid ossification was significantly associated with the diagnosis of PRS (P<0.05). Only ni-PRS patients showed a significant reduction of the distance between hyoid and mandible compared to the control group (P<0.001). Hyoid volume was significantly lower only in the ni-PRS group than in controls (P<0.001). CONCLUSION: I-PRS and ni-PRS patients differ both etiologically and clinically. Ni-PRS patients confirmed their worst clinical condition than i-PRS with severe anomalies of hyoid development, helping for their ontogeny classification.

Do hydrofluorocarbons destroy stratospheric ozone?

Hydrofluorocarbons, many of which contain a CF(3) group, are one of the major substitutes for the chlorofluorocarbons and halons that are being phased out because they contribute to stratospheric ozone depletion. It is critical to ensure that CF(3) groups do not cause significant ozone depletion. The rate coefficients for the key reactions that determine the efficiency of the CF(3) radical as a catalyst for ozone loss in the stratosphere have been measured and used in a model to calculate the possible depletion of ozone. From these results, it is concluded that the ozone depletion potentials related to the presence of the CF(3) group in hydrofluorocarbons are negligibly small.

Biomechanical Effects of Different Auxiliary-Aligner Designs for the Extrusion of an Upper Central Incisor: A Finite Element Analysis.

Aim: To evaluate the biomechanical effects of four different auxiliary-aligner combinations for the extrusion of a maxillary central incisor and to define the most effective design through finite element analysis (FEA). Materials and Methods: A full maxillary arch (14 teeth) was modelled by combining two different imaging techniques: cone beam computed tomography and surface-structured light scan. The appliance and auxiliary element geometries were created by exploiting computer-aided design (CAD) procedures. The reconstructed digital models were imported within the finite element solver (Ansys® 17). For the extrusion movement, the authors compared the aligner without an attachment with three auxiliary-aligner designs: a rectangular palatal attachment, a rectangular buccal attachment, and an ellipsoid buccal attachment. The resulting force-moment (MF) system delivered by the aligner to the target tooth and the tooth displacement were calculated for each scenario. Results: The maximum tooth displacement along the z-axis (0.07 mm) was obtained with the rectangular palatal attachment, while the minimum (0.02 mm) was obtained without any attachments. With the ellipsoid attachment, the highest undesired moments M x and M y were found. The rectangular palatal attachment showed the highest F z (2.0 N) with the lowest undesired forces (F x = 0.4 N; F y = -0.2 N). Conclusions: FEA demonstrated that the rectangular palatal attachment can improve the effectiveness of the appliance for the extrusion of an upper central incisor.

Keratoprosthesis prophylaxis: is it time for a paradigm shift?

The Boston Type I Keratoprosthesis has been improving in both design and safety since its inception. Due to particular features inherent in the Boston Type I Keratoprosthesis eye and certain aspects of the ocular surface, special attention is required to maintain these implanted devices. There is currently a prominent role for keratoprosthesis prophylaxis; it is designed to prevent infectious complications like keratitis and endophthalmitis. This standard-of-care therapy has anecdotally been shown to improve outcomes; however, it has not been examined in the setting of controlled clinical trials. Moreover, concerns remain with the chronic utilization of topical antibiotics in that they may engender antibiotic resistance and select for opportunistic populations to establish a foothold on the ocular surface. We believe and introduce the idea that there is merit in exploring other compounds besides antibiotics for prophylaxis such as antiseptics like povidone-iodine. Specifically developed formulations of povidone-iodine may prove useful in both improving keratoprosthesis safety and simultaneously mitigating concerns regarding antibiotic resistance.

Pierre Robin sequence: A comprehensive narrative review of the literature over time.

Pierre Robin syndrome (PRS) is characterized of a triad of clinical signs: micrognathia, glossoptosis and obstruction of the upper airways frequently associated with palatal cleft. It is a heterogenic pathological entity and it can be found as isolated disease (nsPRS) or in association with other syndromes (sPRS), with more pronounced symptoms and systemic involvement. This review aims to summarize the principal features of PRS, analysing the different aspects of the disease. Epidemiological data highlight incidence, severity and mortality of PRS; pathophysiological mechanism reports the etiology and pathogenesis of the disease distinguishing between isolated and syndromic form. Because of the clinical importance of PRS, it's fundamental to describe the features of the Robin sequence to clearly define its primary and secondary clinical signs useful to diagnosis. A complete evaluation of the syndrome allows choosing the most appropriate therapeutic treatment, opting for conservative or surgical management, in order to improve the quality of life of the patient.

Evaluation of developmental neurotoxicity of organotins via drinking water in rats: dimethyl tin.

Dimethyltin (DMT) is one of several organotins that are detected in domestic water supplies due to their use as plastic stabilizers for polyvinyl chloride (PVC) and chlorinated PVC (CPVC) products. A limited number of in vitro and in vivo studies suggest that DMT may produce developmental neurotoxicity; therefore, we initiated studies to evaluate long-term neurobehavioral changes in offspring following perinatal exposure. In the first study, female Sprague-Dawley rats were exposed via drinking water to DMT (0, 3, 15, 74 ppm) before mating and throughout gestation and lactation. Male offspring were tested for changes in: 1) preweaning learning in an associative runway task, 2) motor activity ontogeny, 3) spatial learning and retention in the Morris water maze as adults, 4) brain weight, 5) biochemical evidence of apoptosis, and 6) neuropathology. DMT toxicity was expressed as depressed maternal weight gain (74 ppm), and in the offspring, decreased brain weight (3, 74 ppm), decreased apoptosis (all concentrations), mild vacuolation in adult offspring (all concentrations), and slower learning in the water maze (15 ppm) due to altered spatial search patterns. In a second study, DMT exposure (same concentrations) occurred from gestational day 6 to weaning. Male and female offspring were tested. The high concentration again depressed maternal weight gain, decreased offspring birth weight and preweaning growth, and decreased brain weight. Increased and decreased apoptotic markers were measured, depending on age. Learning deficits were observed in the runway at postnatal day 11 (15, 74 ppm) and again in the adult offspring in the water maze (15 ppm). The results of both studies demonstrate a reproducible effect of 15 ppm perinatal DMT exposure on spatial learning. Changes in expression of apoptosis, brain weight, and the occurrence of neuropathological lesions also indicate potential neurotoxicity of DMT. These results were in contrast to earlier findings with monomethyl tin, for which only similar neuropathological lesions were observed. Thus, developmental neurotoxicity may be produced in offspring following gestational exposure to DMT in drinking water.

Computational design and engineering of polymeric orthodontic aligners.

Transparent and removable aligners represent an effective solution to correct various orthodontic malocclusions through minimally invasive procedures. An aligner-based treatment requires patients to sequentially wear dentition-mating shells obtained by thermoforming polymeric disks on reference dental models. An aligner is shaped introducing a geometrical mismatch with respect to the actual tooth positions to induce a loading system, which moves the target teeth toward the correct positions. The common practice is based on selecting the aligner features (material, thickness, and auxiliary elements) by only considering clinician's subjective assessments. In this article, a computational design and engineering methodology has been developed to reconstruct anatomical tissues, to model parametric aligner shapes, to simulate orthodontic movements, and to enhance the aligner design. The proposed approach integrates computer-aided technologies, from tomographic imaging to optical scanning, from parametric modeling to finite element analyses, within a 3-dimensional digital framework. The anatomical modeling provides anatomies, including teeth (roots and crowns), jaw bones, and periodontal ligaments, which are the references for the down streaming parametric aligner shaping. The biomechanical interactions between anatomical models and aligner geometries are virtually reproduced using a finite element analysis software. The methodology allows numerical simulations of patient-specific conditions and the comparative analyses of different aligner configurations. In this article, the digital framework has been used to study the influence of various auxiliary elements on the loading system delivered to a maxillary and a mandibular central incisor during an orthodontic tipping movement. Numerical simulations have shown a high dependency of the orthodontic tooth movement on the auxiliary element configuration, which should then be accurately selected to maximize the aligner's effectiveness.

CT segmentation of dental shapes by anatomy-driven reformation imaging and B-spline modelling.

Dedicated imaging methods are among the most important tools of modern computer-aided medical applications. In the last few years, cone beam computed tomography (CBCT) has gained popularity in digital dentistry for 3D imaging of jawbones and teeth. However, the anatomy of a maxillofacial region complicates the assessment of tooth geometry and anatomical location when using standard orthogonal views of the CT data set. In particular, a tooth is defined by a sub-region, which cannot be easily separated from surrounding tissues by only considering pixel grey-intensity values. For this reason, an image enhancement is usually necessary in order to properly segment tooth geometries. In this paper, an anatomy-driven methodology to reconstruct individual 3D tooth anatomies by processing CBCT data is presented. The main concept is to generate a small set of multi-planar reformation images along significant views for each target tooth, driven by the individual anatomical geometry of a specific patient. The reformation images greatly enhance the clearness of the target tooth contours. A set of meaningful 2D tooth contours is extracted and used to automatically model the overall 3D tooth shape through a B-spline representation. The effectiveness of the methodology has been verified by comparing some anatomy-driven reconstructions of anterior and premolar teeth with those obtained by using standard tooth segmentation tools. Copyright © 2015 John Wiley & Sons, Ltd.

Qualitative and quantitative estimates of apoptosis from birth to senescence in the rat brain.

Apoptosis is crucial for proper development of the CNS, wherein a significant percentage of all central neurons produced during early ontogeny die by apoptosis. To characterize the pattern of developmental programmed cell death, we assayed rat brainstem, neocortex, hippocampus, and cerebellum from birth through senescence. Quantitatively, using an ELISA for oligonucleosomal DNA fragments, we demonstrated that PND1 brainstem, neocortex, and hippocampus have the highest levels of fragmented DNA compared to older ages. Cerebellum displayed a large peak at PND10 and a smaller peak at PND21. Low levels were observed throughout adulthood and into senescence, which was corroborated qualitatively by agarose gel and TUNEL data. These data provide a temporal and regional baseline for further studies of the effects of perturbations of cell death during neural development. Quantitative and qualitative changes in these regional profiles of apoptosis due to environmental insults during early ontogeny may alter neuron number and function later in life.

Neurotoxic effects of neonatal triethyltin (TET) exposure are exacerbated with aging.

Neonatal Long-Evans rats dosed with TET (5 mg/kg; IP) or saline on postnatal day (PND) 10 were examined across the life span for neural damage and performance on spatial learning tasks. A subset of rats were sacrificed to assess early damage with Nissl-staining, Timm's histochemistry, and glial fibrillary acidic protein (GFAP) immunohistochemistry 2, 7, or 14 days after dosing. Littermates were tested behaviorally in a T-maze spatial delayed alternation task on PND 23 or PND 90, and in a Morris water maze place learning task at 3, 12, or 24 months postdosing and then sacrificed for histological analysis. In neonatal rats, histological analysis indicated gliosis in discrete cortical regions, loss of Nissl-stained neurons in the hippocampal formation, entorhinal cortex and piriform cortex, and loss of Timm's staining in the entorhinal cortex. The behavioral assessment at PND 23 indicated a significant impairment in the T-maze. However, no significant impairments were observed in the T-maze at 3 months or the water maze at 3 or 12 months postdosing. At 24 months, TET-treated rats showed significant deficits in acquisition and retention of the water maze task compared with age-matched controls. Both groups of 24 months old rats were significantly impaired compared with young controls. At 24 months, there was a general age-related decrease in the optical density of Timm's staining in cortical regions (9%), compounded by a further decrease in the entorhinal cortex and outer molecular layer of the dentate gyrus of the hippocampus in TET treated rats (30%). These data indicate that early developmental exposure to an organometal resulted in morphological damage that was apparent behaviorally only during early postnatal development and with advanced aging.

Adenosine analogs with covalently attached lipids have enhanced potency at A1-adenosine receptors.

Chemically functionalized congeners of N6-phenyladenosine and 1,3-dipropyl-8-phenylxanthine have been covalently coupled to fatty acids, diglycerides, and a phospholipid. The lipid-drug conjugates inhibit R-[3H]-phenylisopropyladenosine binding to A1-adenosine receptors in rat cerebral cortex membranes. A xanthine-phosphatidylethanolamine conjugate bound with a Ki value of 19 nM. Various xanthine esters of low potency are potential prodrugs. Amides of an adenosine amine congener (ADAC) with 18-carbon fatty acids exhibited Ki values at A1-adenosine receptors of 70 pM, representing a 130-fold enhancement over the affinity of the corresponding acetyl amide. The very high affinity of adenosine-lipid conjugates may be due to stabilization of these adducts in the phospholipid microenvironment of the receptor protein.

Electrophilic derivatives of purines as irreversible inhibitors of A1 adenosine receptors.

Functionalized congeners derived from 1,3-dipropyl-8-phenylxanthine and from N6-phenyladenosine were derivatized to contain electrophilic groups (isothiocyanate, N-hydroxysuccinimide ester, maleimide, sulfonyl chloride, or alpha-haloacyl group) capable of reaction with nucleophiles on biopolymers. The goal was to inhibit chemically the A1 adenosine receptor by using reactive agonist and antagonist ligands. Some of the electrophilic derivatives were synthesized through acylation of amine-functionalized congeners using hetero- or homobifunctional reagents available for protein cross-linking. The affinity for A1 adenosine receptors was evaluated in competitive binding assays by using rat and bovine brain membranes. Several xanthine and adenosine thiourea derivatives prepared from 1,3- and 1,4-phenylene diisothiocyanate (DITC) were potent irreversible inhibitors of adenosine receptors. Derivatives of m-DITC, at concentrations between 10 and 500 nM, irreversibly eliminated binding at 90% of the A1-receptor sites. Receptor affinity of both xanthine and adenosine derivatives containing distal phenylthiourea substituents was diminished by electron-donating groups on the ring.

Sulfur-containing 1,3-dialkylxanthine derivatives as selective antagonists at A1-adenosine receptors.

Sulfur-containing analogues of 8-substituted xanthines were prepared in an effort to increase selectivity or potency as antagonists at adenosine receptors. Either cyclopentyl or various aryl substituents were utilized at the 8-position, because of the association of these groups with high potency at A1-adenosine receptors. Sulfur was incorporated on the purine ring at positions 2 and/or 6, in the 8-position substituent in the form of 2- or 3-thienyl groups, or via thienyl groups separated from an 8-aryl substituent through an amide-containing chain. The feasibility of using the thienyl group as a prosthetic group for selective iodination via its Hg2+ derivative was explored. Receptor selectivity was determined in binding assays using membrane homogenates from rat cortex [( 3H]-N6-(phenylisopropyl)adenosine as radioligand] or striatum [3H]-5'-(N-ethylcarbamoyl)adenosine as radioligand] for A1- and A2-adenosine receptors, respectively. Generally, 2-thio-8-cycloalkylxanthines were at least as A1 selective as the corresponding oxygen analogue. 2-Thio-8-aryl derivatives tended to be more potent at A2 receptors than the oxygen analogue. 8-[4-[(Carboxy-methyl)oxyl] phenyl]-1,3-dipropyl-2-thioxanthine ethyl ester was greater than 740-fold A1 selective.