A Role Beyond Learning for NMDA Receptors in Reward-Based Decision-Making—a Pharmacological Study Using d-Cycloserine

N-methyl-D-aspartate (NMDA) receptors are known to fulfill crucial functions in many forms of learning and plasticity. More recently, biophysical models, however, have suggested an additional role of NMDA receptors in evidence integration for decision-making, going beyond their role in learning. We designed a task to study the role of NMDA receptors in human reward-guided learning and decision-making. Human participants were assigned to receive either 250 mg of the partial NMDA agonist d-cycloserine (n=20) or matching placebo capsules (n=27). Reward-guided learning and decision-making were assessed using a task in which participants had to integrate learnt and explicitly shown value information to maximize their monetary wins and minimize their losses. To tease apart the effects of NMDA on learning and decision-making we used simple learning models. D-cycloserine shifted decision-making towards a more optimal integration of the learnt and the explicitly shown information, in the absence of a direct learning effect. In conclusion, our results reveal a distinct role for NMDA receptors in reward-guided decision-making. We discuss these findings in the context of NMDA''s roles in neuronal super-additivity and as crucial for evidence integration for decisions.     

Common and specific brain responses to scenic emotional stimuli

Processing of emotions has been an enduring topic of interest in neuroimaging research, but studies have mostly used facial emotional stimuli. The aim of this study was to determine neural networks involved in emotion processing using scenic emotional visual stimuli. One hundred and twenty photographs from the International Affective Picture System (IAPS), including ecological scenes of disgust, fear, happiness, and sadness, were presented to 40 healthy participants while they underwent functional magnetic imaging resonance (fMRI). Afterwards they evaluated the emotional content of the pictures in an offline task. The occipito-temporal cortex and the amygdala–hippocampal complex showed a non-specific emotion-related activation, which was more marked in response to negative emotions than to happiness. The temporo-parietal cortex and the ventral anterior cingulate gyrus showed deactivation, with the former being marked for all emotions except fear and the latter being most marked for disgust. The fusiform gyrus showed activation in response to disgust and deactivation in response to happiness or sadness. Brain regions involved in processing of scenic emotion therefore resemble those reported for facial expressions of emotion in that they respond to a range of different emotions, although there appears to be specificity in the intensity and direction of the response.     

Moderate acute exercise (70% VO2 peak) induces TGF‐β, α‐amylase and IgA in saliva during recovery

Strenuous exercise promotes changes in salivary IgA and can be associated with a high incidence of upper respiratory tract Infections. However, moderate exercise enhances immune function. The effect of exercise on salivary IgA has been well studied, but its effect on other immunological parameters is poorly studied. Thus, this study determined the effect of moderate acute exercise on immunological salivary parameters, such as the levels of cytokines (TGF‐β and IL‐5), IgA, α‐amylase and total protein, over 24 h. Ten male adult subjects exercised for 60 min at an intensity of 70% VO₂ peak. Saliva samples were collected before (‘basal’) and 0, 12 and 24 h after an exercise session. The total salivary protein was lower after 12 and 24 h than immediately after exercise, whereas α‐amylase increased at 12 and 24 h after exercise compared with basal levels. The IgA concentration was increased at 24 h after exercise relative to immediately after exercise, and there was no difference in the IL‐5 while TGF‐β concentration increased in recovery. In conclusion, 70% VO₂ peak exercise does not induce changes immediately after exercise, but after 24 h, it produces an increase in salivary TGF‐β without changing IL‐5.     

Endovascular treatment of a Superior Mesenteric Artery Syndrome variant secondary to traumatic pseudoaneurysm

Pseudoaneurysms related to the superior mesenteric artery (SMA) are a recognised complication of trauma to the vessel, and successful treatment with stenting has been previously described. We report the case of a patient who presented with obstruction of the fourth part of the duodenum secondary to a traumatic pseudoaneurysm, a hitherto unreported variant of superior mesenteric artery syndrome. Exclusion of the pseudoaneurysm and relief of the duodenal obstruction were simultaneously achieved by placement of a covered stent.     

Usefulness and side effects of a diet rich in vegetable fiber in insulin-dependent diabetic adolescents

The influence on metabolic control and the possible side effects of a diet rich in vegetable fibers was evaluated in a group of insulin-dependent diabetic adolescents. After two weeks of controlled diet, a new dietary regime with a higher vegetable fiber content (66 g/day vs 15 g/day) and an increased iron content (22.5 mg/day vs 11.5 mg/day) was assigned to each patient for a period of two months. At the end of the dietary trial, a decrease of the insulin requirement, of the mean daily blood glucose values, and of glycosylated haemoglobin (HbA1) was observed. Serum iron levels were statistically lowered, but still in the normal range. These data suggest that high fiber diet can improve metabolic control of type I diabetes, but cast some doubts because of possible side effects on intestinal absorption of oligo-elements.     

Boar semen controlled delivery system: analysis of batch seasonal variability

A new encapsulation technology of swine semen is proposed to improve the quality of stored spermatozoa and to obtain the controlled release of viable cells, reducing the number of instrumental inseminations. This technology has been employed to produce barium alginate gel capsules in different seasons; an analysis of batch reproducibility was performed, and total capsule diameter, gel thickness and weight of capsules were determined as indices of batch properties. A seasonal variability was found but each batch was substantially homogeneous. The variability could be related to the biological variability of the semen employed as raw material as well as to the technological process.     

Barium alginate cell-delivery systems: correlation between technological parameters

The most recent trends for the development of several in vitro cell cultures have been oriented towards the cell immobilisation in 3-dimensional scaffolds and cell encapsulation. In fact, an important requirement of cell survival is self-assembly in functional communities, in the presence of an artificial extracellular matrix. In our research, a previously described technique for spermatozoa encapsulation was applied to obtain capsules loaded with an opaque agent as a model, and to perform a formulative study. A process variable, barium ion concentration, was correlated to some capsule properties, such as weight, gel thickness, total and core diameter. Ion concentration can be modified to obtain capsules with predictable characteristics.     

Pilot study of oral rapamycin to prevent restenosis in patients undergoing coronary stent therapy: Argentina Single-Center Study (ORAR Trial)

Rapamycin-coated stents are associated with low restenosis rates, but the ability of oral rapamycin to prevent restenosis is unknown. From December 2001 through February 2002, thirty-four patients with 49 lesions were treated with oral rapamycin for 1 month following percutaneous coronary intervention (PCI) with bare stents. Patients received a loading dose of 6 mg rapamycin followed by a daily dose of 2 mg. Rapamycin blood levels were measured in all patients during the third week of treatment. Cholesterol and triglycerides were evaluated before and 1 month after treatment. A 6-month follow-up angiogram was performed in all patients. Angiographic binary restenosis (> 50%), target lesion revascularization (TLR), late loss, treatment compliance and major adverse cardiac events were analyzed independent of rapamycin levels. Baseline characteristics included a history of diabetes in 35% of patients and the presence of in-stent restenosis in 24.5% of lesions (12/49). The rapamycin was well tolerated and only 1 patient discontinued the therapy due to mild side effects. Angiographic restenosis and TLR at 6 months was present in 26.5% of lesions (13/49). Restenosis in de novo lesions was 18.9% (7/37) compared to 50% of in-stent restenotic lesions (6/12; p = 0.08). Restenosis in de novo lesions in patients with rapamycin levels > 8 ng/ml was 0% (0/12), whereas it was 24% (6/25) when the rapamycin levels were < 8 ng/ml (p = 0.07). Late loss was significantly lower when rapamycin levels were > 8 ng/ml (0.3 mm versus 0.9 mm, respectively; p = 0.04). Thus, in this observational study, oral rapamycin administered for 1 month after PCI with bare stenting was safe and well tolerated. Higher therapeutic rapamycin blood levels were associated with a lower late loss and a trend toward a lower restenosis rate in de novo lesions.     

Low activity of 13-cis-retinoic acid plus interferon alpha 2a in advanced renal cell carcinoma

Retinoids and interferon alpha have shown synergistic activity against metastatic renal cell carcinoma in previous preclinical and clinical studies. Based on these results, we conducted a phase II trial of 13-cis-retinoic acid (cRA) at 1 mg/kg/dose interferon alpha2a (IFN) at initial dose of 9 MU three times a week. Thirty-one patients were entered, all evaluable for toxicity and 30 evaluable for response. One patient achieved a partial response and 10 patients achieved stable disease. Toxicity was mild and primarily related to interferon. No toxic deaths were reported. Median survival time was 10 months. At the dose and schedule used, cRA and interferon-alpha2a showed low activity against metastatic renal cell carcinoma. Further studies with this combination are not recommended.     

Factors predictive of response and survival in patients with metastatic colorectal cancer in Taiwan

5-Fluorouracil in combination with leucovorin has been shown to be active in therapeutic trials of metastatic colorectal carcinoma. In this study, we administered these drugs to 72 patients with metastatic colorectal carcinoma. Thirty-six of them without previous exposure to 5-fluorouracil were treated with weekly bolus injections of 5-fluorouracil (425 mg/m2) and leucovorin (25 mg/m2) supplemented with oral levamisole. Another 36 patients with or without prior 5-fluorouracil treatment received 5-fluorouracil 3,000 mg/m2 and leucovorin 300 mg/m2 in a 48-hour continuous infusion every two weeks. Clinical efficacy and toxicity were assessed by WHO criteria. Variables were tested for relations to response and survival by univariate and multivariate analysis. The response rate was 19.4% in weekly bolus arm and 13.9% in biweekly high-dose infusion arm (P = 0.527). Median survivals in the two arms were 18.4 months (weekly) and 21 months (biweekly) respectively (P = 0.708). Gastrointestinal side effects including nausea, vomiting, diarrhea and mucositia were the major toxicities of these regimens. By multivariate analysis, the only factor to influence response rate was the site of metastases (P = 0.009). The only factor to affect survival was performance status of the patient (P = 0.0001). We concluded that the two 5-fluorouracil based regimens are well-tolerated and shown to have a response rate comparable with previous reports of similar regimens in patients with metastatic colorectal cancer. Only liver metastases seemed to have a better response to therapy. Performance status is the most important prognostic factor in patients with metastatic colorectal cancer.