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.     

Fixation of displaced femoral neck fractures: A comparison between sliding screw plate and four cancellous bone screws

In a prospective, randomized trial, 104 consecutive patients with displaced femoral neck fractures were allocated either to fixation with a sliding screw plate or 4 ASIF cancellous bone screws. The patients were reexamined at fixed intervals to determine the time of union. The 2-year-cumulated rate of union was 64 per cent in the plate group and 84 per cent in the screw group.     

A simple mechanical model using a piston to produce localized cerebral contusions in pigs

Summary A simple mechanical model using a piston to produce localized cerebral contusions in pigs, is presented.The precision and reproducibility of the method are described by the biomechanical and pathological results.There are only pathological changes with haemorrhage and laceration close to the place of entry of the piston. The changes in the physiological parameters also indicate that the damage is focal.In this model, when kept intact, the dura mater offers considerable protection as no pathological changes in the brain are observed even when the energy at the time of the contusion is increased to twice the values which, when the dura is open, cause considerable damage.     

The role of preimplantation sonographic exposure in postimplantation development and pregnancy outcome.

To determine what, if any, effects exposure to ultrasonic beams has on preimplantation embryos we isolated mouse blastocysts and assessed resorption rate, pregnancy rate, decidual swelling volume, and live birth rate after in vitro exposure with subsequent transfer to surrogate mothers. The blastocyst stage embryos were isolated by flushing the uteri of pregnant animals with a phosphate buffered medium. Blastocysts at a discrete stage of development were pooled and transferred to a PB1-methylcellulose medium. This medium is specifically designed to maintain the embryos in a high viscosity solution during the sonographic exposure to prevent microcavitation. After the exposure, the embryos were washed free of methylcellulose and transferred to the uteri of pseudopregnant surrogate mothers. A total of 660 blastocyst stage embryos were distributed among seven treatment groups. After exposure, the embryos were transferred to 54 surrogate mothers. A total of 199 embryos were implanted successfully for postimplantation evaluation. An additional 427 blastocysts were distributed among four treatment groups and transferred to 46 surrogate mothers to assess the effect of sonographic exposure on birth rate. The results indicate possible deleterious effects (decreased implantation rate, increased resorption rate, decreased decidual swelling volume, and increased stillbirth rate) of short ultrasonic exposures (1 min and 5 min) on mouse blastocyst function.     

Intercalated cells of the rat inner medullary collecting duct

There is increasing evidence of acidification along the entire mammalian collecting duct including the inner medullary collecting duct (IMCD). Recent studies have provided morphologic evidence that the intercalated cells are involved in hydrogen ion secretion in the cortical and outer medullary collecting duct of the rat. In the present study we performed a quantitative and qualitative morphologic examination of the intercalated cells in the IMCD of the rat and compared the results to observations obtained from intercalated cells in the collecting duct in the inner stripe of the outer medulla (OMCDi). Kidneys of male rats were preserved by in vivo perfusion with glutaraldehyde and processed for morphologic evaluation. With light microscopy and scanning electron microscopy intercalated cells were found in the outer third of the IMCD (IMCD1) and accounted for 10% of the total cell population. They were absent in the terminal two-thirds of the IMCD. Examination of the intercalated cells using transmission electron microscopy revealed striking similarities between the cells of the IMCD1 and those in the OMCDi. In addition, no differences were found in the surface densities of the apical or basolateral plasma membranes or the volume densities of the mitochondria of the intercalated cells in the two regions. In light of the morphologic similarity with the intercalated cells of the OMCDi that are believed to be involved in hydrogen ion secretion, it is likely that the intercalated cells of the IMCD1 are also involved in the acidification of tubular fluid.     

Effects of prenalterol on central hemodynamics and myocardial metabolism in experimental propoxyphene-induced shock

The hemodynamic and cardiometabolic effects of prenalterol were evaluated in propoxyphene-induced circulatory shock in 10 pentobarbital-anesthetized pigs. Circulatory shock (i.e. a systolic arterial blood pressure below 60 mmHg (8 kPa) and/or a cardiac index of less than 2.0 1 X min-1 X m-2) was induced by intravenous propoxyphene chloride 15 mg X min-1. Circulatory shock occurred after 26 +/- 3 mg X kg-1 of propoxyphene. During continuous infusion of propoxyphene, consecutive doses of prenalterol 0.5, 1.0, 2.0 and 4.0 mg i.v. were injected with an interval between increments of 8 min. The maximum effect of prenalterol was seen following the 2 mg dose. Increases were observed in mean arterial blood pressure, cardiac index, stroke volume index, left ventricular stroke work index, right ventricular stroke work index, maximum rate of rise of ventricular pressure, and total body oxygen consumption. Decreases were observed in pulmonary artery occlusion pressure, mean right atrial pressure and systemic vascular resistance, whereas heart rate and pulmonary vascular resistance remained unchanged. The cardiometabolic parameters: coronary sinus flow, coronary vascular resistance, myocardial oxygen consumption and extraction, remained low. Due to profound vasodilation, normal perfusion pressures were not reestablished. In conclusion, prenalterol improved cardiac performance by a significant positive inotropic action. However, pure inotropic stimulation was not sufficient to counteract the circulatory shock state during severe propoxyphene intoxication.     

S-100β Protein – Serum Levels in Children with Brain Neoplasms and its Potential as a Tumor Marker

OBJECTIVE: To determine if serum S-100beta levels are elevated in children with brain neoplasms and if it can be used as a tumor marker for children with brain neoplasms. DESIGN: Prospective cohort study. SETTING: Urban, tertiary care, children's teaching hospital. PATIENTS: 136 healthy children and 27 children with brain neoplasms. METHODS: Serum levels of S-100beta were measured in 136 healthy children to serve as controls and 27 children with brain neoplasms, who underwent biopsy or resection of the mass. Patients were then classified into astrocytoma or non-astrocytoma groups. MEASUREMENTS AND MAIN RESULTS: The median serum S-100beta level for the control group was 0.27 mcg/l (range, 0.06-2.6 mcg/l), and for the brain neoplasm group was 0.2 mcg/l (range, 0.01-2.1 mcg/l), (p = 0.09). There were 13 children with astrocytomas and 14 with non-astrocytomas. The S-100beta levels for the astrocytoma group was 0.25 mcg/l (range, 0.05-1.1 mcg/l) and for the non-astrocytoma group 0.17 mcg/l (range, 0.01-2.1 mcg/l), (p = 0.47). CONCLUSIONS: Serum S-100beta levels are not elevated in children with brain neoplasms compared to healthy children, nor are they elevated in children with astrocytomas compared to non-astrocytomas. The S-100beta protein does not appear to be useful as a serum tumor marker in children with brain neoplasms.     

Inhibiting hydrogen sulfide production in umbilical stem cells reduces their protective effects during experimental necrotizing enterocolitis

IntroductionUmbilical mesenchymal stem cells (USC) have been shown to reduce illness in animal models of necrotizing enterocolitis (NEC), possibly through the paracrine release of hydrogen sulfide (H₂S). We hypothesized that animals treated with USCs with inhibited H₂S synthesis would exhibit more severe disease.MethodsNEC was induced in five-day-old mouse pups by formula feeding and hypoxic and hypothermic stress. Experimental groups received intraperitoneal injection of either saline vehicle or 80,000cells/gram of one of the following cell types: USC, USCs with negative-control siRNA, or USCs with targeted siRNA inhibition of the H₂S-producing enzymes. Pups were monitored by clinical assessment and after euthanasia, intestine and lung histologic injury were scored. Tissue was homogenized, and concentrations of IL-6, IL-10, and VEGF were determined by ELISA. For statistical analysis, p < 0.05 was considered significant.ResultsAnimals treated with negative-control siRNA USCs were significantly improved compared to vehicle. Clinical sickness scores as well as intestinal and lung histologic injury scores in the targeted siRNA groups were significantly worse when compared to the negative-control siRNA group. IL-6, IL-10, and VEGF had varying patterns of expression in the different groups.ConclusionInhibition of H₂S production in USCs reduces the beneficial effects of these cells during therapy in experimental NEC.Level of evidenceAnimal studies are typically described as “foundational evidence” without a true level assigned.Type of studyAnimal Study.