Adenosine neuromodulation depends on a balanced activation of inhibitory A 1 (A 1 R) and facilitatory A 2A receptors (A 2A R). Both A 1 R and A 2A R modulate hippocampal glutamate release and NMDA-dependent long-term potentiation (LTP) but ageing affects the density of both A 1 R and A 2A R. We tested the effects of selective A 1 R and A 2A R antagonists in the modulation of synaptic transmission and plasticity in rat hippocampal slices from three age groups (young adults, 2-3 month; middle-aged adults, 6-8 months; aged, 18-20 months). The selective A 2A R antagonist SCH58261 (50 nm) attenuated LTP in all age groups, with a larger effect in aged ()63 ± 7%) than in middle-aged adults ()36 ± 9%) or young adult rats ()36 ± 9%). In contrast, the selective A 1 R antagonist DPCPX (50 nm) increased LTP magnitude in young adult rats (+42 ± 6%), but failed to affect LTP magnitude in the other age groups. Finally, in the continuous presence of DPCPX, SCH58261 caused a significantly larger inhibition of LTP amplitude in aged ()71 ± 45%) than middle-aged ()28 ± 9%) or young rats ()11 ± 2%). Accordingly, aged rats displayed an increased expression of A 2A R mRNA in the hippocampus and a higher number of glutamatergic nerve terminals equipped with A 2A R in aged (67 ± 6%) compared with middle-aged (34 ± 7%) and young rats (25 ± 5%). The results show an enhanced A 2A R-mediated modulation of LTP in aged rats, in accordance with the age-associated increased expression and density of A 2A R in glutamatergic terminals. This age-associated gain of function of A 2A R modulating synaptic plasticity may underlie the ability of A 2A R antagonists to prevent memory dysfunction in aged animals.

BackgroundGastric cancer (GC) is one of the most common malignant tumors of the digestive tract and is the third leading cause of cancer death worldwide. Epstein–Barr virus (EBV) has been associated with approximately 10% of the total cases of gastric carcinomas. No previous study has analyzed the prevalence of EBV infection in gastric cancer of the Portuguese population.MethodsIn the present study, we have analyzed 82 gastric carcinoma cases and 33 healthy individuals (control group) from Coimbra region for the presence of EBV by polymerase chain reaction (PCR) and by in situ hybridization (ISH) for EBV-encoded small RNAs (EBERs). The status of H. pylori infection was assessed by serology and by PCR.ResultsEBV was detected by PCR in 90.2% of stomach cancer cases, whereas EBERs were detected in 11%. In our series, EBV-associated gastric carcinoma (EBVaGC) were significantly associated with gender and the majority of them presented lymph node metastasis. These cases were generally graded in more advanced pTNM stages and, non-surprisingly, showed worse survival. H. pylori infection was detected in 62.2% of the gastric cancers and 64.7% of these patients were CagA+. On the other hand, the H. pylori prevalence was higher in the EBV-negative gastric carcinomas (64.4%) than in those carcinoma cases with EBV+ (44.4%).ConclusionsThe present study shows that prevalence of EBVaGC among Portuguese population is in accordance with the worldwide prevalence. EBV infection seems to be associated to poorer prognostic and no relation to H. pylori infection has been found. Conversely, the presence of H. pylori seems to have a favourable impact on patient’s survival. Our results emphasize that geographic variation can contribute with new epidemiological data on the association of EBV with gastric cancer.

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In the hippocampus, impaired neurophysiology, compromised neurogenesis, and eventually apoptosis accompany cognitive deficits in insulinopenic (type-1) diabetes (T1D). The underlying pathological mechanisms remain to be defined. The hippocampus has a high density of the cannabinoid type 1 receptor (CB 1 R), which has been shown to control several brain functions affected by diabetes, such as synaptic plasticity, glucose utilisation, memory consolidation and cognition, and maturation and survival of hippocampal neurons. However, the role of this receptor has not been investigated yet in diabetic encephalopathy. We report now that in the streptozotocin animal model of T1D, the hippocampal densities of CB 1 R protein and of specific CB 1 R binding sites are significantly increased both in the nerve terminals and in total membranes (changes between 13% and 38%), whereas CB 1 R mRNA expression is decreased by 25%, suggesting that CB 1 Rs might play a role in diabetic encephalopathy.

Introduction:Viral protein R (Vpr) of human immunodeficiency virus type 1 (HIV-1) has been described as being involved in the progression of AIDS, and specific mutations are associated with long-term non-progressor patients.Case presentation:We describe the case of a child with repeated ear infections who was otherwise healthy. The patient, a 5-year-old boy, was HIV-1 positive and the viral load at admission was 1 073 899 RNA copies ml−1 and 0 % CD4+ lymphocytes. A detailed study of the vpr gene sequence of the child revealed mutations leading to amino acid substitutions at positions 3 and 77.Conclusion:The case reported provides clinical support of previous findings that show that the R77Q and Q3R HIV-1 Vpr variants are associated with patients with delayed disease progression.