392 research outputs found
Somatostatin receptor scintigraphy in cutaneous malignant lymphomas
Background: Lymphoid cells may express somatostatin receptors (SS-Rs) on their cell surface.
Therefore radiolabeled somatostalin analogues may be used to visualize SS-R-positive
lymphoid neoplasms in vivo. Exact staging is the basis for treatment decisions in cutaneous
malignant lymphoma. We considered the possibility that SS-R scintigraphy might offer a
clinically useful method of diagnostic imaging in patients with cutaneous malignant
lymphoma.
Objective: We evaluated SS-R scintigraphy in comparison with conventional staging methods
in the staging of cutaneous malignant lymphoma.
Methods: We conducted a prospective study in 14 consecutive patients with histologically
proven cutaneous malignant lymphoma. SS-R scintigraphy was compared with physical, radiologic,
and bone marrow examinations. Lymph node excisions were performed in patients
with palpable lymph nodes.
Results: SS-R scintigraphy was positive in the lymph nodes in all four patients with malignant
lymph node infiltration and negative in the three patients with dermatopathic lymphadenopathy.
In two patients, previously unsuspected lymphoma localizations were visualized by
SS-R scintigraphy. In only three patients all skin lesions were visualized by SS-R scintigraphy;
these three patients had not been treated with topical corticosteroids. SS-R scintigraphy
failed to detect an adrenal mass in one patient and bone marrow infiltration in two patients.
Conclusion: SS-R scintigraphy may help distinguish dermatopathic lymphadenopathy from
malignant lymph node infiltration in patients with cutaneous malignant lymphoma
Hormonal crises following receptor radionuclide therapy with the radiolabeled somatostatin analogue [177Lu-DOTA0,Tyr 3]octreotate
Introduction: Receptor radionuclide therapy is a promising treatment modality for patients with neuroendocrine tumors for whom alternative treatments are limited. The aim of this study was to investigate the incidence of hormonal crises after therapy with the radiolabeled somatostatin analogue [177Lu-DOTA0,Tyr3]octreotate (177Lu-octreotate). Materials and methods: All177Lu- octreotate treatments between January 2000 and January 2007 were investigated. Four hundred seventy-six patients with gastroenteropancreatic neuroendocrine tumors and three patients with metastatic pheochromocytoma were included fo
The hibernation-derived compound SUL-138 shifts the mitochondrial proteome towards fatty acid metabolism and prevents cognitive decline and amyloid plaque formation in an Alzheimer’s disease mouse model
Background: Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease worldwide and remains without effective cure. Increasing evidence is supporting the mitochondrial cascade hypothesis, proposing that loss of mitochondrial fitness and subsequent ROS and ATP imbalance are important contributors to AD pathophysiology. Methods: Here, we tested the effects of SUL-138, a small hibernation-derived molecule that supports mitochondrial bioenergetics via complex I/IV activation, on molecular, physiological, behavioral, and pathological outcomes in APP/PS1 and wildtype mice. Results: SUL-138 treatment rescued long-term potentiation and hippocampal memory impairments and decreased beta-amyloid plaque load in APP/PS1 mice. This was paralleled by a partial rescue of dysregulated protein expression in APP/PS1 mice as assessed by mass spectrometry-based proteomics. In-depth analysis of protein expression revealed a prominent effect of SUL-138 in APP/PS1 mice on mitochondrial protein expression. SUL-138 increased the levels of proteins involved in fatty acid metabolism in both wildtype and APP/PS1 mice. Additionally, in APP/PS1 mice only, SUL-138 increased the levels of proteins involved in glycolysis and amino acid metabolism pathways, indicating that SUL-138 rescues mitochondrial impairments that are typically observed in AD. Conclusion: Our study demonstrates a SUL-138-induced shift in metabolic input towards the electron transport chain in synaptic mitochondria, coinciding with increased synaptic plasticity and memory. In conclusion, targeting mitochondrial bioenergetics might provide a promising new way to treat cognitive impairments in AD and reduce disease progression
Evaluation in vitro and in rats of161Tb-DTPA-octreotide, a somatostatin analogue with potential for intraoperative scanning and radiotherapy
The characteristics of terbium-161 diethylene triamine penta-acetic acid (DTPA) labelled octreotide with respect to specific binding to somatostatin (octreotide) receptors on rat brain cortex membranes, biological activity, uptake and excretion by isolated perfused rat livers and metabolism in vivo in normal and tumour-bearing rats were determined and compared to those of indium-111 DTPA-octreotide. The results of the binding studies demonstrate that161Tb-DTPA-octreotide is a high-affinity radioligand for somatostatin receptors, with an affinity comparable to that of111In-DTPA-octreotide. Rat growth hormone secretion inhibition experiments showed that161Tb-DTPA-octreotide has a similar potency to111In-DTPA-octreotide.161Tb-DTPA-octreotide appeared to be taken up even less by the isolated perfused rat liver than111In-DTPA-octreotide, as almost no tracer disappeared from the perfusion medium. Furthermore, hardly any radioactivity was found in the liver, and excretion into the bile was negligible. The biodistribution studies showed that for octreotide receptor-positive organs, such as pancreas and adrenals, uptake of161Tb-DTPA-octreotide is lower then that of111In-DTPA-octreotide. However, as the clearance from the blood of the former compound is faster than that of the latter, the tissue/blood ratio is higher in the case of161Tb-DTPA-octreotide than with111In-DTPA-octreotide. Furthermore, these studies demonstrated that the uptake of161Tb-DTPA-octreotide by the renal tubular cells after glomerular filtration can be reduced by administration of lysine or sodium maleate. Increase in urine production before and during the experiment had no effect on the kidney uptake of161Tb-DTPA-octreotide. Finally, it appeared that a maximal labelling efficiency of161Tb-DTPA-octreotide is essential, as with decreasing efficiency the uptake in the octreotide receptor-positive organs decreased, whereas non-specific uptake in the other organs was increased. It is concluded that, on the basis of the favourable physical characteristics of161Tb combined with the in vitro and in vivo studies performed with161Tb-DTPA-octreotide, the latter is a promising radiopharmaceutical for both intraoperative scanning and radiotherapy. Studies in patients need to be performed now to see whether161Tb-DTPA-octreotide can indeed open new therapeutic applications for patients bearing octreotide receptor-positive tumours
Visualization of the thymus by substance P receptor scintigraphy in man
Substance P, an 11-amino acid neuropeptide, has an important role in modulating pain transmission through neurokinin 1 and 2 receptors. Substance P and other tachykinins may also play a role in the pathogenesis of inflammatory diseases. In this study we present the results concerning the metabolism of the substance P analogue [111In-DTPA-Arg1]-substance P in man, as well as the visualization of the thymus in patients with immune-mediated diseases. Twelve selected patients were investigated, comprising five with inflammatory bowel disease, one with ophthalmic Graves' disease, one with sclerosing cholangitis, one with Sjogren's syndrome, one with rheumatoid arthritis, one with systemic lupus erythematosus and two with myasthenia gravis. During and after intravenous administration of 150-250 MBq (2.5-5.0 ÎĽg) [111In-DTPA-Arg1]-substance P, blood pressure, heart rate and oxygen saturation were monitored. Radioactivity was measured in blood, urine and faeces during the 48 h after injection. Planar and single-photon emission tomographic images were obtained 4 and 24 h after injection. After administration of [111In-DTPA-Arg1]-substance P a transient flush was observed in all patients. Degradation of [111In-DTPA-Arg1] -substance P started in the first minutes after administration, resulting in a half-life of 10 min for the total plasma radioactivity, and of 4 min for the intact radiopharmaceutical, as identified with high-performance liquid chromatography. Urinary excretion accounted for >95% of the radioactivity within 24 h post injection, and up to 0.05% was found in the faeces up to 60 h. In all patients uptake of radioactivity was found in the areolae mammae (in women), liver, spleen, kidneys and urinary bladder. In eight patients a high uptake of [111In-DTPA-Arg1]-substance P was observed in the thymus. We conclude that, despite its short half-life. [111In-DTPA-Arg1]-substance P, a new radiopharmaceutical, can be used to visualize the thymus. This may contribute to the investigation of the role of thymus in immune-mediated diseases. In addition, inflammatory sites in various diseases could be visualized.</p
Visualization of the thymus by substance P receptor scintigraphy in man
Substance P, an 11-amino acid neuropeptide, has an important role in modulating pain transmission through neurokinin 1 and 2 receptors. Substance P and other tachykinins may also play a role in the pathogenesis of inflammatory diseases. In this study we present the results concerning the metabolism of the substance P analogue [111In-DTPA-Arg1]-substance P in man, as well as the visualization of the thymus in patients with immune-mediated diseases. Twelve selected patients were investigated, comprising five with inflammatory bowel disease, one with ophthalmic Graves' disease, one with sclerosing cholangitis, one with Sjogren's syndrome, one with rheumatoid arthritis, one with systemic lupus erythematosus and two with myasthenia gravis. During and after intravenous administration of 150-250 MBq (2.5-5.0 ÎĽg) [111In-DTPA-Arg1]-substance P, blood pressure, heart rate and oxygen saturation were monitored. Radioactivity was measured in blood, urine and faeces during the 48 h after injection. Planar and single-photon emission tomographic images were obtained 4 and 24 h after injection. After administration of [111In-DTPA-Arg1]-substance P a transient flush was observed in all patients. Degradation of [111In-DTPA-Arg1] -substance P started in the first minutes after administration, resulting in a half-life of 10 min for the total plasma radioactivity, and of 4 min for the intact radiopharmaceutical, as identified with high-performance liquid chromatography. Urinary excretion accounted for >95% of the radioactivity within 24 h post injection, and up to 0.05% was found in the faeces up to 60 h. In all patients uptake of radioactivity was found in the areolae mammae (in women), liver, spleen, kidneys and urinary bladder. In eight patients a high uptake of [111In-DTPA-Arg1]-substance P was observed in the thymus. We conclude that, despite its short half-life. [111In-DTPA-Arg1]-substance P, a new radiopharmaceutical, can be used to visualize the thymus. This may contribute to the investigation of the role of thymus in immune-mediated diseases. In addition, inflammatory sites in various diseases could be visualized.</p
Epigenetics in the primary and secondary prevention of cardiovascular disease: influence of exercise and nutrition
Increasing evidence links changes in epigenetic systems, such as DNA methylation, histone modification, and non-coding RNA expression, to the occurrence of cardiovascular disease (CVD). These epigenetic modifications can change genetic function under influence of exogenous stimuli and can be transferred to next generations, providing a potential mechanism for inheritance of behavioural intervention effects. The benefits of exercise and nutritional interventions in the primary and secondary prevention of CVD are well established, but the mechanisms are not completely understood. In this review, we describe the acute and chronic epigenetic effects of physical activity and dietary changes. We propose exercise and nutrition as potential triggers of epigenetic signals, promoting the reshaping of transcriptional programmes with effects on CVD phenotypes. Finally, we highlight recent developments in epigenetic therapeutics with implications for primary and secondary CVD prevention
Modern meningioma imaging techniques
Steady improvements in imaging modalities have enabled a new realm of capabilities in the identification and assessment of meningiomas. The cross-sectional imaging modalities, MRI and CT, have improved in resolution and fidelity. These modalites now provide not only improved structural information but also insights into functional behavior. MRI has, in particular, proven to have powerful capabilities in evaluating meningiomas because of the ability to assess soft tissue characteristics such as diffusion and vascular supply information, such as perfusion. Recent investigational advances have also been made using a combination of X-ray fluoroscopy for selective catheterization followed by MR perfusion measurement performed with intra-arterial injection of contrast. Together all these modalities provide the radiographer with powerful capbilities for evaluating meningiomas
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