Adenosine A2A and dopamine D2 heteromeric receptor complexes and their function

The existence of A2A-D2 heteromeric complexes is based on coimmunoprecipitation studies and on fluorescence resonance energy transfer and bioluminescence resonance energy transfer analyses. It has now become possible to show that A2A and D2 receptors also coimmunoprecipitate in striatal tissue, giving evidence for the existence of A2A-D2 heteromeric receptor complexes also in rat striatal tissue. The analysis gives evidence that these heteromers are constitutive, as they are observed in the absence of A2A and D2 agonists. The A2A-D2 heteromers could either be A2A-D2 heterodimers and/or higher-order A2A -D2 hetero-oligomers. In striatal neurons there are probably A2A-D2 heteromeric complexes, together with A2A-D2 homomeric complexes in the neuronal surface membrane. Their stoichiometry in various microdomains will have a major role in determining A2A and D2 signaling in the striatopallidal GABA neurons. Through the use of D2/D1 chimeras, evidence has been obtained that the fifth transmembrane (TM) domain and/or the I3 of the D2 receptor are part of the A2A-D2 receptor interface, where electrostatic epitope-epitope interactions involving the N-terminal part of I3 of the D2 receptor (arginine-rich epitope) play a major role, interacting with the carboxyl terminus of the A2A receptor. Computerized modeling of A2A-D2 heteromers are in line with these findings. It seems likely that A2A receptor-induced reduction of D2 receptor recognition, G protein coupling, and signaling, as well as the existence of A2A-D2 co-trafficking, are the consequence of the existence of an A2A-D2 receptor heteromer. The relevance of A2A-D2 heteromeric receptor complexes for Parkinson's disease and schizophrenia is emphasized as well as for the treatment of these diseases. Finally, recent evidence for the existence of antagonistic A2A-D3 heteromeric receptor complexes in cotransfected cell lines has been summarized.     

Morphine and alternative opioids in cancer pain: the EAPC recommendations

An expert working group of the European Association for Palliative Care has revised and updated its guidelines on the use of morphine in the management of cancer pain. The revised recommendations presented here give guidance on the use of morphine and the alternative strong opioid analgesics which have been introduced in many parts of the world in recent years. Practical strategies for dealing with difficult situations are described presenting a consensus view where supporting evidence is lacking. The strength of the evidence on which each recommendation is based is indicated.     

Baboon syndrome

The cases of three children diagnosed with baboon syndrome are described, being defined by the appearance of dermatological lesions, with characteristic distribution and morphology, as a result of having been in contact with mercury. Other substances have been described associated with the appearance of this syndrome; however their pathogenis is not completely known, and it has been suggested that it could be another form of contact dermatitis. Diagnosis is based on patient clinical history and physical examination and there is no specific treatment.     

Comparative 3D finite element stress analysis of straight and angled wedge-shaped implant designs

PURPOSE: The goal of this work was to analyze the stress distribution in 2 wedge-shaped implant designs, straight and angled, by means of a 3-dimensional finite element method (FEM) stress analysis. MATERIALS AND METHODS: A model was generated from computerized tomography of a human edentulous mandible with the implants placed in the left first molar region. The model included boundary conditions representing the muscles of mastication and the temporomandibular joint. An axial load of 100 N and a horizontal load of 20 N were separately applied at the tops of the implant abutments, and system equilibrium equations were used to find each muscle intensity force based on its position and direction. The mandibular boundary conditions were modeled considering the anatomy of the supporting muscle system. Cortical and medullary bones were assumed to be homogeneous, isotropic, and linearly elastic. RESULTS: The stress analysis provided results in terms of normal maximum tensile (sigma1) and compressive (sigma3) stress fields. The stress distribution was quite similar for both designs, indicating a good performance of the angled design. CONCLUSIONS: Stresses in the angled implant were in general lower than in the straight implant, and the differences between the 2 designs studied were more relevant for the vertical load. No indication was found that angled implants of the type described generate stress-induced problems compared to straight implants.     

Polycondensation of Metal Salts of 6‐(2‐Chloroacetate)hexanoic Acid: A New Method to Synthesize Alternating Copolyesters Constituted by Glycolic Acid Units

A new copolyester was prepared from glycolic acid and 6‐hydroxyhexanoic acid units. The monomer was prepared by a thermal polycondensation method and its reactivity evaluated by means of DSC and IR spectroscopy. The driving force of the reaction was the formation of a metal chloride salt. Thus, the reactivity depended on the ionization potential of the alkaline cation; while the cesium salt started to polymerize at room temperature, the sodium salt did so only above 120 °C. The low reaction temperature and the absence of catalysts allowed transesterification and other secondary reactions to be avoided. DSC, optical microscopy and XRD techniques demonstrated that the new polymer was highly crystalline. The final molecular weight was sufficient to obtain fiber‐forming properties.