Adenosine A(2A) receptor facilitation of hippocampal synaptic transmission is dependent on tonic A(1) receptor inhibition

Adenosine tonically inhibits synaptic transmission through actions at A(1) receptors. It also facilitates synaptic transmission, but it is unclear if this facilitation results from pre- and/or postsynaptic A(2A) receptor activation or from indirect control of inhibitory GABAergic transmission. The A(2A) receptor agonist, CGS 21680 (10 nM), facilitated synaptic transmission in the CA1 area of rat hippocampal slices (by 14%), independent of whether or not GABAergic transmission was blocked by the GABA(A) and GABA(B) receptor antagonists, picrotoxin (50 microM) and CGP 55845 (1 microM), respectively. CGS 21680 (10 nM) also inhibited paired-pulse facilitation by 12%, an effect prevented by the A(2A) receptor antagonist, ZM 241385 (20 nM). These effects of CGS 21680 (10 nM) were occluded by adenosine deaminase (2 U/ml) and were made to reappear upon direct activation of A(1) receptors with N(6)-cyclopentyladenosine (CPA, 6 nM). CGS 21680 (10 nM) only facilitated (by 17%) the K(+)-evoked release of glutamate from superfused hippocampal synaptosomes in the presence of 100 nM CPA. This effect of CGS 21680 (10 nM), in contrast to the isoproterenol (30 microM) facilitation of glutamate release, was prevented by the protein kinase C inhibitors, chelerythrine (6 microM) and bisindolylmaleimide (1 microM), but not by the protein kinase A inhibitor, H-89 (1 microM). Isoproterenol (30 microM), but not CGS 21680 (10-300 nM), enhanced synaptosomal cAMP levels, indicating that the CGS 21680-induced facilitation of glutamate release involves a cAMP-independent protein kinase C activation. To discard any direct effect of CGS 21680 on adenosine A(1) receptor, we also show that in autoradiography experiments CGS 21680 only displaced the adenosine A(1) receptor antagonist, 1,3-dipropyl-8-cyclopentyladenosine ([(3)H]DPCPX, 0.5 nM) with an EC(50) of 1 microM in all brain areas studied and CGS 21680 (30 nM) failed to change the ability of CPA to displace DPCPX (1 nM) binding to CHO cells stably transfected with A(1) receptors.Our results suggest that A(2A) receptor agonists facilitate hippocampal synaptic transmission by attenuating the tonic effect of inhibitory presynaptic A(1) receptors located in glutamatergic nerve terminals. This might be a fine-tuning role for adenosine A(2A) receptors to allow frequency-dependent plasticity phenomena without compromising the A(1) receptor-mediated neuroprotective role of adenosine.     

Gonococcal endocarditis: a rare complication of a common disease

This report describes a case of gonococcal endocarditis in a 28 year old male patient with no history of previous valvular heart disease. More cases of gonococcal endocarditis (a rare complication of gonorrhoea) may occur with the increase in the incidence of gonorrhoea and the increase in resistance to ciprofloxacin, which is currently used as the first line agent for the treatment of gonorrhoea in 75% of genitourinary medicine clinics.     

Implementing a Transition Program from Paediatric to Adult Services in Phenylketonuria: Results after Two Years of Follow-Up with an Adult Team

We aimed to report the implementation of a phenylketonuria (PKU) transition program and study the effects of follow-up with an adult team on metabolic control, adherence, and loss of follow-up. Fifty-five PKU patients were analysed in the study periods (SP): 2 years before (SP1) and after the beginning of adult care (SP2). Retrospective data on metabolic control and number of clinic appointments were collected for each SP, and protein intakes were analysed. In SP2, three patients (6%) were lost to follow-up. There was a small but statistically significant increase in median number of annual blood spots from SP1 to SP2: 11 (7–15) vs. 14 (7–20); p = 0.002. Mean ± SD of median blood Phe remained stable (525 ± 248 µmol/L vs. 552 ± 225 µmol/L; p = 0.100); median % of blood Phe < 480 µmol/L decreased (51 (4–96)% vs. 37 (5–85)%; p = 0.041) and median number of clinic appointments increased from SP1 to SP2: (5 (4–6) vs. 11 (8–13); p < 0.001). No significant differences were found regarding any parameter of protein intake. Our results suggest that the implementation of an adult service was successful as impact on metabolic control was limited and attendance remained high. Continuous dietetic care likely contributed to these results by keeping patients in follow-up and committed to treatment.     

Correction to: Incidence and characteristics of methicillin‑resistant coagulase‑negative Staphylococcus in peritoneal dialysis‑associated peritonitis in a single center using molecular methods

International Urology and Nephrology - In the original publication, article title was incorrectly published.     

Orofacial evaluation of individuals with temporomandibular disorder after LED therapy associated or not of occlusal splint: a randomized double-blind controlled clinical study

Lasers in Medical Science - This study compared the effects of LED therapy associated with occlusal splint (OS) on the signs and symptoms of temporomandibular disorder (TMD). In this randomized,...     

The influence of photobiomodulation on the temperature of the brachial biceps during muscle fatigue protocol

Lasers in Medical Science - Physical activity raises body temperature. However, the literature does not contain studies about whether the employment of hotobiomodulation (PMB) could significantly...     

Being on hemodialysis during the COVID‐19 outbreak: A mixed‐methods’ study exploring the impacts on dialysis adequacy,analytical data,and patients’ experiences

For individuals with end‐stage renal disease (ESRD), the novel coronavirus can present several additional challenges in disease self‐management. This study aimed to explore the impacts of the COVID‐19 pandemic in non‐COVID‐19 patients with ESRD undergoing in‐center hemodialysis (HD). A mixed‐methods study was conducted with a purposive sample recruited from one dialysis unit in Portugal. Quantitative data were collected retrospectively from patients' medical records from February 2020 (T1—before the outbreak) and from April 2020 (T2—during lockdown). Semi‐structured interviews were conducted with 20 patients (66.9 ± 11.9 years old) undergoing HD for an average of 46.1 months (±39.5) in April 2020. Overall results suggested that dialysis adequacy and serum albumin levels decreased significantly at T2, while phosphorus levels increased. The findings from thematic analysis suggested several psychosocial negative impacts and impacts on disease and treatment‐related health behaviors (eg, difficulties managing dietary restrictions during the lockdown and diminished physical activity), which can partially explain these quantitative results. However, some patients were also able to find positive impacts in this experience and problem‐focused and emotional strategies were identified to cope with the demands of COVID‐19. Several recommendations have been made to mitigate patients’ emotional, relational, and educational unmet needs during the current pandemic and in the event of new outbreaks.     

Predictive factors of recurrence in adenocarcinoma of the esophagogastric junction in the multimodal era

IntroductionAdenocarcinoma of the esophagogastric junction (AEGJ) represents a poor prognostic tumor. We evaluated the recurrence pattern and risk factors associated with recurrence in patients undergoing surgical resection by AEJG.MethodsRecurrences were categorized as locoregional, peritoneal, or distant. These three recurrence groups and a non-recurrence group were compared, and overall survival (OS) and disease-free survival (DFS) for each one was obtained.ResultsWe analyzed 188 patients with curative surgical treatment. Recurrence was observed in 72 (38.3%) patients. Locoregional recurrence was observed in 17 (23.6%); 20 (27.8%) peritoneal recurrence and 35 (48.6%) distant metastasis. DFS was 9, 5, and 8 months, and OS was 21.8, 13.2, and 20.8, respectively. Tumors larger than 5 cm are risk factors for peritoneal recurrence (OR:2.88, p = 0.012). Positive lymph nodes were related to distant metastasis (OR:9.15, p = 0.040), and lymphatic invasion for locoregional recurrence (OR:3.81, p = 0.028).ConclusionAEGJ is associated with high rates of early recurrence.