Cognitive function is related to fronto-striatal serotonin transporter levels �C a brain PET study in young healthy subjects

Rationale

Pharmacological manipulation of serotonergic neurotransmission in healthy volunteers impacts on cognitive test performance. Specifically, markers of serotonin function are associated with attention and executive functioning, long-term memory, and general cognitive ability. The serotonin transporter (SERT) protein is a key regulator in the serotonin system. We hypothesized that higher performance on tests sensitive to serotonin would be associated with higher SERT levels in specific fronto-striatal brain regions.

Methods

Thirty-two healthy subjects (25 males, mean age 26.0?years, range 19?C37) underwent positron emission tomography using the SERT ligand [¹¹C]DASB. Subjects underwent the following tests: Stroop Color Word Test, Trail Making Test B, Rey??s Auditory Verbal Learning Test and Complex Figure Test, logical reasoning subtest from Intelligenz-Struktur-Test 2000 R, and a Danish version of National Adult Reading Test.

Results

We found positive associations between performance on the Stroop Color Word Test and right-sided dorsolateral prefrontal SERT binding (R ²?=?0.12, p?=?0.048). Furthermore, scores of logical reasoning (correlating with IQ) and educational level associated positively with SERT binding in the caudate, most prominent on the left side (logical reasoning: R ²?=?0.34, p?=?0.0026 (left), R ²?=?0.2, p?=?0.022 (right), educational level: R ²?=?0.19, p?=?0.012 (left), R ²?=?0.15, p?=?0.027 (right)). Scores of logical reasoning also associated with left-sided ventrolateral prefrontal cortex (R ²?=?0.24, p?=?0.014). There were no significant associations between SERT binding and tests of long-term episodic memory.

Conclusions

The results imply that in healthy subjects, high SERT binding in fronto-striatal regions is associated with better performance on tasks involving executive function and logical reasoning.     

Diffuse reflectance spectrophotometry with visible light: comparison of four different methods in a tissue phantom

The purpose of the study was to compare algorithms of four methods (plus two modifications) for spectrophotometric haemoglobin saturation measurements. Comparison was made in tissue phantoms basically consisting of a phosphate buffer, Intralipid and blood, allowing samples to be taken for reference measurements. Three experimental series were made. In experiment A (eight phantoms) we used the Knoefel method and measured specific extinction coefficients with a reflection spectrophotometer. In experiment B (six phantoms) the fully oxygenated phantoms were gradually deoxygenated with baker's yeast, and simultaneous measurements were made with our spectrophotometer and with a reference oxymeter (ABL-605) in 3 min intervals. For each spectrophotometric measurement haemoglobin saturation was calculated with all algorithms and modifications, and compared with reference. In experiment C (11 phantoms) we evaluated the ability of a modification of the Knoefel method to measure haemoglobin concentration in absolute quantities using extinction coefficients from experiment A.Results. Experiment A: with the Knoefel method extinction coefficients (+/-SD) for oxyhaemoglobin at 553.04 and 573.75 nm were 1.117 (+/-0.0396) ODmM(-1) and 1.680 (+/- 0.0815) ODmM(-1), respectively, and for deoxyhaemoglobin 1.205 (+/- 0.0514) ODmM(-1) and 0.953 (+/-0.0487) ODmM(-1), respectively. Experiment B: high correlation with the reference was found in all methods (r = 0.94-0.97). However, agreement varied from evidently wrong in method 3 and the original method 4 (e.g. saturation above 160%) to high agreement in method 2 as well as the modifications of methods 1 and 4, where oxygen dissociation curves were close to the reference method. Experiment C: with the modified Knoefel method the mean haemoglobin concentration difference from reference was 8.3% and the correlation was high (r = 0.91).We conclude that method 2 and the modifications of 1 and 4 were superior to the others, but depended on known values in the same or similar phantoms. The original method 1 was independent of results from the tissue phantoms, but agreement was slightly poorer. Method 3 and the original method 4 could not be recommended. The ability of the modified method 1 to measure haemoglobin concentration is promising, but needs further development.     

Thiamine reverses hyperglycemia-induced dysfunction in cultured endothelial cells.

BACKGROUND: High levels of glucose have previously been shown to inhibit endothelial cell migration and increase secretion of the von Willebrand factor (vWF), a marker of endothelial cell damage. This study investigates whether thiamine, an important coenzyme in intracellular glucose metabolism, improves endothelial cell migration and decreases von Willebrand factor secretion under hyperglycemic conditions. METHODS: Bovine aortic endothelial cells (BAECs) were grown under physiological glucose (5.5 mmol/L) and hyperglycemic (13.8 mmol/L and 27.7 mmol/L) conditions with or without thiamine (200 micromol/L) supplementation. Endothelial cell migration was investigated in monolayers of BAECs that were wounded by scraping. The distance of migration, the number of migrating cells, and the surface area covered by the migrating cells were measured. Secretion of vWF by BAECs under physiological glucose and high glucose conditions with or without thiamine (200 micromol/L) supplementation was studied with enzyme-linked immunosorbent assay. RESULTS: Under hyperglycemic conditions, there was a significant decrease in the number of endothelial cells and an increase in the secretion of vWF (P <.001). Thiamine treatment limited this inhibitory effect of elevated glucose levels on BAECs. Glucose (27.7 mmol/L) significantly decreased the migration distance of BAECs into the wounded area to 4.0 +/- 1.4 cm, as compared with 6.2 +/- 0.3 cm in the control. Thiamine supplementation restored the migration distance by BAECs (6.94 +/- 0.7 cm) and the wound surface area covered (47.7 +/- 5.6 cm(2)) (P <.001). CONCLUSIONS: Hyperglycemia activates BAECs and promotes secretion of vWF, a marker of endothelial cell damage. Thiamine inhibits this endothelial cell activation and the effects of hyperglycemia on endothelial cell migration. This beneficial effect of thiamine limiting endothelial cell dysfunction is possibly through the diversion of glucose flux from anaerobic to aerobic pathways. The data from this study lead to the speculation that thiamine intake may mitigate or delay vascular complications of diabetes.     

Monounsaturated fatty acids in serum triacylglycerols are associated with response to neoadjuvant chemotherapy in breast cancer patients

Changes in cellular lipid metabolism are a common feature in most solid tumors, which occur already in early stages of the tumor progression. However, it remains unclear if the tumor‐specific lipid changes can be detected at the level of systemic lipid metabolism. The objective of this study was to perform comprehensive analysis of lipids in breast cancer patient serum samples. Lipidomic profiling using an established analytical platform was performed in two cohorts of breast cancer patients receiving neoadjuvant chemotherapy. The analyses were performed for 142 patients before and after neoadjuvant chemotherapy, and the results before chemotherapy were validated in an independent cohort of 194 patients. The analyses revealed that in general the tumor characteristics are not reflected in the serum samples. However, there was an association of specific triacylglycerols (TGs) in patients' response to chemotherapy. These TGs containing mainly oleic acid (C18:1) were found in lower levels in those patients showing pathologic complete response before receiving chemotherapy. Some of these TGs were also associated with estrogen receptor status and overall or disease‐free survival of the patients. The results suggest that the altered serum levels of oleic acid in breast cancer patients are associated with their response to chemotherapy.     

Infection Rates Following Hepatic Embolotherapy in Patients with Prior Biliary Interventions: Comparison of Single-Drug Moxifloxacin and Multidrug Antibiotic Prophylaxis

PurposeTo investigate the incidence of infection in patients with prior biliary interventions undergoing hepatic embolotherapy following extended antibiotic prophylaxis using moxifloxacin monotherapy or a multidrug regimen.Material and methodsUnder an Institutional Review Board-approved protocol, retrospective review of a quality assurance database identified all liver-directed therapies (LDTs) at a tertiary care center between 2010 and 2019 with biliary intervention prior to LDT Records were reviewed for infectious complications within 3 months of chemo- or radioembolization. Patients were categorized based on extended antibiotic prophylaxis regimen: oral moxifloxacin monotherapy or multidrug regimen of levofloxacin and metroniodazole plus preprocedural neomycin and erythromycin. Procedures without at least 2 months of clinical follow-up, hepatic ablation, and procedures without extended antibiotic prophylaxis were excluded Regression analysis was used to analyze multivariate data to detect a difference in infection rate.ResultsTwenty-four chemoembolization and 58 radioembolization procedures were performed on 55 patients with prior biliary interventions. Forty-four used monotherapy and 38 used multidrug regimen. The incidence of infection was 16.7% (4/24) after chemoembolization and 13.8% (8/58) after radioembolization The incidence of infection in patients did not differ between antibiotic prophylaxis regimens (18.2% [8/44] with moxifloxacin monotherapy and 10.5% [4/38] multidrug regimen, P = .3) or between types of biliary interventions (24.1% [7/29] with bilioenteric anastomosis and 23.8% [5/21] biliary stenting, P = .3).ConclusionsThe types of extended antibiotic prophylaxis (moxifloxacin monotherapy vs multitherapy), prior biliary intervention, and embolotherapy were not found to be associated with differences in the incidence of infectious complications in this population.     

Temporal gradient in the remote memory impairment of amnesic patients with lesions in the basal forebrain

Recall and recognition of premorbid public events were studied in four groups of subjects. Dementia patients showed equal losses from all time periods compared to normal controls. In contrast, two groups of amnesic patients showed extensive remote memory losses, which were most marked for the last few years prior to onset. The difference between recall and recognition was similar in the groups. The results indicate that the retrograde amnesia associated with aneurysms of the anterior communicating artery cannot be distinguished from that of amnesia with other etiologies. Implications of the finding of a temporal gradient in the retrograde amnesia of non-alcoholic amnesics are discussed.     

Nocturnal electroencephalogram registrations in Type 1 (insulin-dependent) diabetic patients with hypoglycaemia

Summary Eight Type 1 (insulin-dependent) diabetic patients with no diabetic complications were studied overnight for two consecutive and one subsequent night with continuous monitoring of electroencephalogram and serial hormone measurements. The aims were: 1) to evaluate the influence of spontaneous and insulin-induced hypoglycaemia on nocturnal electroencephalogram sleep-patterns and, 2) to evaluate counter-regulatory hormone responses. Spontaneous hypoglycaemia occurred on six nights (38%) with blood glucose concentrations <3.0 mmol/l and on four nights <2.0 mmol/l. All the patients experienced insulin-induced hypoglycaemia with a blood glucose nadir of 1.6 (range 1.4–1.9) mmol/l. The electroencephalogram was analysed by a new method developed for this purpose in contrast to the traditional definition of delta-, theta-, alpha- and beta-activity. The blood glucose concentration could be correlated to the rank of individual electroencephalogram-patterns during the whole night, and specific hypoglycaemic amplitude-frequency patterns could be assigned. Three of the eight patients showed electroencephalogram changes at blood glucose levels below 2.0 (1.6–2.0) mmol/l. The electroencephalogram classes representing hypoglycaemic activity had peak frequencies at 4 and 6 Hz, respectively, clearly different from the patients' delta- and theta-activity. The changes were not identical in each patient, however, they were reproducible in each patient. The changes were found equally in all regions of the brain. The three patients with electroencephalogram changes during nocturnal hypoglycaemia could only be separated from the other five patients by their impaired glucagon responses. Against this background the possibility of protection by glucagon, against neurophysiologic changes in the brain during hypoglycaemia may be considered.