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Sample records for acting somatostatin analog

  1. Conversion of daily pegvisomant to weekly pegvisomant combined with long-acting somatostatin analogs, in controlled acromegaly patients

    NARCIS (Netherlands)

    S.J.C.M.M. Neggers (Bas); W.W. de Herder (Wouter); R.A. Feelders (Richard); A-J. van der Lely (Aart-Jan)

    2011-01-01

    textabstractThe efficacy of combined treatment in active acromegaly with both long-acting somatostatin analogs (SRIF) and pegvisomant (PEG-V) has been well established. The aim was to describe the PEG-V dose reductions after the conversion from daily PEG-V to combination treatment. To clarify the

  2. Treatment adherence and persistence with long-acting somatostatin analog therapy for the treatment of acromegaly: a retrospective analysis.

    Science.gov (United States)

    Gurel, Michelle H; Han, Yi; Stevens, Andrea L; Furtado, Aaron; Cox, David

    2017-04-04

    Many patients with acromegaly require medical treatment that includes somatostatin analogs (SSAs). Long-acting SSA formulations are widely used, due in part to increased patient convenience and increased treatment adherence vs daily medications. Although medication compliance can be poor in patients with chronic conditions, adherence and persistence with these SSAs in patients with acromegaly has not been evaluated. This analysis utilized claims data to estimate treatment adherence and persistence for lanreotide depot and long-acting octreotide in this population. This retrospective analysis used the MarketScan® database (~100 payors, 500 million claims in the US), which was searched between January 2007 and June 2012 to identify patients with acromegaly taking either lanreotide depot or long-acting octreotide. Patients switching treatments were excluded. Treatment adherence was assessed using medication possession ratio (MPR; number of doses dispensed in relation to dispensing period; ≥80% is considered adherent), injection count, and treatment time. Persistence was estimated by Kaplan-Meier analyses and Cox proportional hazards modeling. A washout period, defined as no acromegaly-related prescription activity 180 days prior to the index date, was employed to minimize effects of prior therapy and focus on patients more likely to be treatment-naïve. Altogether 1308 patients with acromegaly receiving a single SSA for treatment (1127 octreotide, 181 lanreotide) who had not switched treatments were identified. Mean MPR in patients with a 180-day washout (n = 663) was 89% for those receiving octreotide (n = 545) and 87% for those receiving lanreotide (n = 118). Median number of days on therapy was 169 (95% CI 135-232) for octreotide patients and 400 (95% CI 232-532) for lanreotide patients. The point estimate of the Cox proportional hazard ratio for stopping treatment was 1.385 for octreotide vs lanreotide (95% CI 1.079-1.777), suggesting a 38

  3. Therapy with radiolabelled somatostatin analogs in neuroendocrine tumors

    International Nuclear Information System (INIS)

    Kunikowska, J.; Krolicki, L.

    2007-01-01

    In the 80's the discovery of somatostatin receptors expression on NET cells enabled the application of somatostatin analogues in diagnosis and therapy. Initially, 'cold' somatostatin analogs were used for therapeutical purpose, with overall good clinical response, but with minimal anti-proliferation effect. Furthermore, radiolabelled receptor-binding peptides have been shown to be an important class of radiopharmaceuticals for tumor diagnosis and therapy with minimal side-effects. Specific binding between receptor on tumor cell and peptide with beta emitting radionuclide act not only on tumor related symptoms but also on tumor cell via radiotoxic effect of beta radiation. Discoveries of next receptor combinations, allow the work over synthesis and applications of next receptors' analogs both in diagnosis and in therapy. Due to complex characteristics of NET's, the use therapeutic 'cocktail' containing the variety analogs may be of great importance. (author)

  4. Forty month follow-up of persistent and difficultly controlled acromegalic patients treated with depot long acting somatostatin analog octreotide

    International Nuclear Information System (INIS)

    Yetkin, D.O.; Boysan, S.N.; Tiryakioglu, O.; Yalin, A.S.; Kadioglu, P.

    2007-01-01

    The objective of the present study was to investigate the effects of octreotide long acting release (S-LAR) preparation on growth hormone (GH) and insulin-like growth factor (IGF)-1 serum concentrations and pituitary tumor size in patients with persistent and difficultly controlled acromegaly even after adjuvant irradiation and/or dopamine agonists. Thirty-three patients with active acromegaly (26 female and 7 male, mean age; 43.94±14.01 standard deviation (SD) years) were included in this study. Patients were evaluated at baseline and at 6, 12, 30 and 40 months for GH, IGF-1, and GH response to oral glucose tolerance test (OGTT) and biliary ultrasonography. Sella MRI was performed at initial and at 40 months. All patients received 20 mg S-LAR. Afterwards, the dosage was titrated to improve individual GH response and reduction of IGF-1 into normal ranges. Basal serum IGF-1 levels decreased from median: 530 μg/l [IQR: 420-600] to 340 μg/l [IQR: 230-460] at 6 months (p=0.01), to 400 μg/l [IQR: 222.4-600] at 12 months (p=0.48), to 396 μg/l [IQR: 318-468] at 30 months (p=0.49), to 482 μg/l [308-580] at 40 months (p=0.47). Nadir GH levels in OGTT fell from 2.70 ng/ml [IQR: 1.35-6.90] to 1.60 ng/ml [IQR: 0.36-4.10] at 6 months (p=0.03), to 0.31 ng/ml [IQR: 0.18-0.65] at 12 months (p<0.0001), to 1.50 ng/ml [IQR: 0.83-4.00] at 30 months (p=0.398) and to 0.89 ng/ml [IQR: 0.58-1.35] at 40 months (p<0.0001). Initially, pituitary adenoma volume was median: 1.18 ml [IQR: 0.08-3.50] and it shrank to 0.21 ml [IQR: 0-2.1] at 40 months (p=0.08). Gallstones were detected in 12 patients and six of them underwent cholecystectomy. S-LAR is an effective treatment regimen in reducing GH and IGF-1 concentrations and as well as in shrinking tumor volume in persistent and difficultly controlled acromegalic patients. (author)

  5. Technetium-99m labeled somatostatin and analogs: synthesis, characterization and in vivo evaluation

    International Nuclear Information System (INIS)

    Amartey, J.K.

    1993-01-01

    Technetium-99m complexes of somatostatin and analogs were synthesized following the introduction of sulfhydryl groups with 2-iminothiolane (Traut's Reagent). In rats the complex was taken up by the liver, kidneys, adrenals, lungs and the pancreas. Analysis of urine samples of treated rats showed that the radiochemicals have reasonably good in vivo stability. This implies that the complexes may be potentially useful for biochemical characterization of somatostatin receptors and also in scintigraphic detection of somatostatin receptor positive tumors, especially for metastatic deposits in patients on somatostatin therapy. (Author)

  6. 99m Tc- la bed somatostatin analogs for imaging somatostatin-receptor-positive tumors

    International Nuclear Information System (INIS)

    Gandomkar, M.; Najafi, R.; Shafiei, A.; Sadat Ebrahimi, E.; Babaie, M.H.; Rabani, M.

    2002-01-01

    Over the least few years, 111 In-DTPA- Octreotide has found widespread clinical applicability, especially in oncology. However limitation, especially concerning availability, imaging properties, and costs, remain and have stimulated research on radiolabeling with many alternative radionuclides. The purpose of this investigation was to labeling somatostatin analogs with 99 m Tc and evaluate their suitability as an agents for in vivo use. Octreotide and Tyr-3-Octreotide were labeled by 99 mTc with direct and indirect methods. Sodium ascorbate and sodium dithionite were used for reduction of cystine bridge and HYNIC was used as bifunctional agents and different co ligands used for labeling by 99 mTc. Yield of labeling, purity, stability, internalisation, binding affinity and biodistribution of peptide conjugates were studied. Direct labeling of octreotide was simple, rapid, efficient and yield was good (%60). K d for binding affinity as high (10 -9 ) but stability was low. Labeling for HYNIC-Tyr-Octreotide had a high yield (>%90), good stability, internalisation and biodistribution. with more experimental work and some improve this peptide-based radiopharmaceuticals can be employed in all nuclear medicine centers as a useful agent for imaging of tumors

  7. Experience with indium-111 and yttrium-90-labeled somatostatin analogs.

    Science.gov (United States)

    Virgolini, I; Traub, T; Novotny, C; Leimer, M; Füger, B; Li, S R; Patri, P; Pangerl, T; Angelberger, P; Raderer, M; Burggasser, G; Andreae, F; Kurtaran, A; Dudczak, R

    2002-01-01

    The high level expression of somatostatin receptors (SSTR) on various tumor cells has provided the molecular basis for successful use of radiolabeled octreotide / lanreotide analogs as tumor tracers in nuclear medicine. Other (nontumoral) potential indications for SSTR scintigraphy are based on an increased lymphocyte binding at sites of inflammatory or immunologic diseases such as thyroid-associated ophthalmology. The vast majority of human tumors seem to over-express the one or the other of five distinct hSSTR subtype receptors. Whereas neuroendocrine tumors frequently overexpress hSSTR2, intestinal adenocarcinomas seem to overexpress more often hSSTR3 or hSSTR4, or both of these hSSTR. In contrast to In-DTPA-DPhe(1)-octreotide (OctreoScan(R)) which binds to hSSTR2 and 5 with high affinity (Kd 0.1-5 nM), to hSSTR3 with moderate affinity (K(d) 10-100 nM) and does not bind to hSSTR1 and hSSTR4, (111)In / (90)Y-DOTA-lanreotide was found to bind to hSSTR2, 3, 4, and 5 with high affinity, and to hSSTR1 with lower affinity (K(d) 200 nM). Based on its unique hSSTR binding profile, (111)In-DOTA-lanreotide was suggested to be a potential radioligand for tumor diagnosis, and (90)Y-DOTA-lanreotide suitable for receptor-mediated radionuclide therapy. As opposed to (111)In-DTPA-DPhe(1)-octreotide and (111)In-DOTA-DPhe(1)-Tyr(3)-octreotide, discrepancies in the scintigraphic results were seen in about one third of (neuroendocrine) tumor patients concerning both the tumor uptake as well as detection of tumor lesions. On a molecular level, these discrepancies seem to be based on a "higherrdquuo; high-affinity binding of (111)In-DOTA-DPhe(1)-Tyr(3)-octreotide to hSSTR2 (K(d) 0.1-1 nM). Other somatostatin analogs with divergent affinity to the five known hSSTR subtype receptors have also found their way into the clinics, such as (99m)Tc-depreotide (NeoSpect(R); NeoTect(R)). Most of the imaging results are reported for neuroendocrine tumors (octreotide analogs) or nonsmall cell

  8. Quality of life is impaired in association with the need for prolonged postoperative therapy by somatostatin analogs in patients with acromegaly

    NARCIS (Netherlands)

    Postma, Mark R; Netea-Maier, Romana T; van den Berg, Gerrit; Homan, Jens; Sluiter, Wim J; Wagenmakers, Margreet A; van den Bergh, Alfons C M; Wolffenbuttel, Bruce H R; Hermus, Ad R M M; van Beek, André P

    OBJECTIVE: To assess the influence of long-acting somatostatin analogs (SSTA) after initial pituitary surgery on long-term health-related quality of life (HR-QoL) in relation to disease control in patients with acromegaly. DESIGN: This is a cross-sectional study in two tertiary referral centers in

  9. Quality of life is impaired in association with the need for prolonged postoperative therapy by somatostatin analogs in patients with acromegaly.

    NARCIS (Netherlands)

    Postma, M.R.; Netea-Maier, R.T.; Berg, G. van den; Homan, J.; Sluiter, W.J.; Wagenmakers, M.A.E.M.; Bergh, A.C. van den; Wolffenbuttel, B.H.R.; Hermus, A.R.M.M.; Beek, A.P. van

    2012-01-01

    OBJECTIVE: To assess the influence of long-acting somatostatin analogs (SSTA) after initial pituitary surgery on long-term health-related quality of life (HR-QoL) in relation to disease control in patients with acromegaly. DESIGN: This is a cross-sectional study in two tertiary referral centers in

  10. Switch from antagonist to agonist after addition of a DOTA chelator to a somatostatin analog

    International Nuclear Information System (INIS)

    Reubi, Jean Claude; Cescato, Renzo; Waser, Beatrice; Erchegyi, Judit; Rivier, Jean E.

    2010-01-01

    Peptide receptor targeting has become an increasingly attractive method to target tumors diagnostically and radiotherapeutically. Peptides linked to a variety of chelators have been developed for this purpose. They have, however, rarely been tested for their agonistic or antagonistic properties. We report here on a somatostatin antagonist that switched to an agonist upon coupling to a DOTA chelator. Two novel somatostatin analogs, 406-040-15 and its DOTA-coupled counterpart 406-051-20, with and without cold Indium labeling, were tested for their somatostatin receptor subtypes 1-5 (sst 1 -sst 5 ) binding affinity using receptor autoradiography. Moreover, they were tested functionally for their ability to affect sst 2 and sst 3 internalization in vitro in HEK293 cells stably expressing the human sst 2 or sst 3 receptor, using an immunofluorescence microscopy-based internalization assay. All three compounds were characterized as pan-somatostatin analogs having a high affinity for all five sst. In the sst 2 internalization assay, all three compounds showed an identical behavior, namely, a weak agonistic effect complemented by a weak antagonistic effect, compatible with the behavior of a partial agonist. Conversely, in the sst 3 internalization assay, 406-040-15 was a full antagonist whereas its DOTA-coupled counterpart, 406-051-20, with and without Indium labeling, switched to a full agonist. Adding the DOTA chelator to the somatostatin analog 406-040-15 triggers a switch at sst 3 receptor from an antagonist to an agonist. This indicates that potential radioligands for tumor targeting should always be tested functionally before further development, in particular if a chelator is added. (orig.)

  11. Somatostatine analogs marked with 99m-TC

    International Nuclear Information System (INIS)

    Obenaus, E; Crudo, J; Edreira, M; Castiglia, S.G. de

    2003-01-01

    The aim of the present work was to study the biological and radiochemical behaviour of two somatostatin analogues, the RC-160 and Tyr 3 Octreotide(TOC) peptides when labeling with 99m Tc by an indirect method using S-Benzoyl- mercaptoacetyl triglycine (MAG3) and hydrazino nicotinamide (HYNIC) as chelating agents. The synthesis of RC160 with S-Benzoyl MAG3 and TOC with HYNIC, for labeling with 99m Tc are also described. The conjugates were prepared on a small scale and labeled with the radionuclide using tricine as coligands for HYNIC conjugates. Chromatographic studies were performed using an HPLC system and radiochemical purities higher than 75% and 95% were obtained respectively. Biodistributions studies in normal Wistar rats were performed and results were correlated with chromatographic and protein binding properties. Lower lipophilicity of the labeled conjugates resulted in a higher renal excretion. HYNIC-TOC complex showed promising results when labeling with 99m Tc using tricine as coligand although higher stability should be found for ternary coligands compared to tricine (Au)

  12. Clinical applications of somatostatin analogs for growth hormone-secreting pituitary adenomas

    Directory of Open Access Journals (Sweden)

    Wang JW

    2014-01-01

    Full Text Available Ji-wen Wang,1,2 Ying Li,3 Zhi-gang Mao,1,2 Bin Hu,1,2 Xiao-bing Jiang,1,2 Bing-bing Song,4 Xin Wang,4 Yong-hong Zhu,4 Hai-jun Wang1,21Department of Neurosurgery and Pituitary Tumor Center, The First Affiliated Hospital, Sun Yat-sen University, 2Key Laboratory of Pituitary Adenoma in Guangdong Province, 3State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 4Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, People's Republic of ChinaAbstract: Excessive growth hormone (GH is usually secreted by GH-secreting pituitary adenomas and causes gigantism in juveniles or acromegaly in adults. The clinical complications involving cardiovascular, respiratory, and metabolic systems lead to elevated morbidity in acromegaly. Control of serum GH and insulin-like growth factor (IGF 1 hypersecretion by surgery or pharmacotherapy can decrease morbidity. Current pharmacotherapy includes somatostatin analogs (SAs and GH receptor antagonist; the former consists of lanreotide Autogel (ATG and octreotide long-acting release (LAR, and the latter refers to pegvisomant. As primary medical therapy, lanreotide ATG and octreotide LAR can be supplied in a long-lasting formulation to achieve biochemical control of GH and IGF-1 by subcutaneous injection every 4–6 weeks. Lanreotide ATG and octreotide LAR provide an effective medical treatment, whether as a primary or secondary therapy, for the treatment of GH-secreting pituitary adenoma; however, to maximize benefits with the least cost, several points should be emphasized before the application of SAs. A comprehensive assessment, especially of the observation of clinical predictors and preselection of SA treatment, should be completed in advance. A treatment process lasting at least 3 months should be implemented to achieve a long-term stable blood concentration. More satisfactory surgical outcomes for noninvasive macroadenomas treated

  13. Clinical applications of somatostatin analogs for growth hormone-secreting pituitary adenomas

    Science.gov (United States)

    Wang, Ji-wen; Li, Ying; Mao, Zhi-gang; Hu, Bin; Jiang, Xiao-bing; Song, Bing-bing; Wang, Xin; Zhu, Yong-hong; Wang, Hai-jun

    2014-01-01

    Excessive growth hormone (GH) is usually secreted by GH-secreting pituitary adenomas and causes gigantism in juveniles or acromegaly in adults. The clinical complications involving cardiovascular, respiratory, and metabolic systems lead to elevated morbidity in acromegaly. Control of serum GH and insulin-like growth factor (IGF) 1 hypersecretion by surgery or pharmacotherapy can decrease morbidity. Current pharmacotherapy includes somatostatin analogs (SAs) and GH receptor antagonist; the former consists of lanreotide Autogel (ATG) and octreotide long-acting release (LAR), and the latter refers to pegvisomant. As primary medical therapy, lanreotide ATG and octreotide LAR can be supplied in a long-lasting formulation to achieve biochemical control of GH and IGF-1 by subcutaneous injection every 4–6 weeks. Lanreotide ATG and octreotide LAR provide an effective medical treatment, whether as a primary or secondary therapy, for the treatment of GH-secreting pituitary adenoma; however, to maximize benefits with the least cost, several points should be emphasized before the application of SAs. A comprehensive assessment, especially of the observation of clinical predictors and preselection of SA treatment, should be completed in advance. A treatment process lasting at least 3 months should be implemented to achieve a long-term stable blood concentration. More satisfactory surgical outcomes for noninvasive macroadenomas treated with presurgical SA may be achieved, although controversy of such adjuvant therapy exists. Combination of SA and pegvisomant or cabergoline shows advantages in some specific cases. Thus, an individual treatment program should be established for each patient under a full evaluation of the risks and benefits. PMID:24421637

  14. Synthesis of a Fluorescently Labeled 68Ga-DOTA-TOC Analog for Somatostatin Receptor Targeting.

    Science.gov (United States)

    Ghosh, Sukhen C; Hernandez Vargas, Servando; Rodriguez, Melissa; Kossatz, Susanne; Voss, Julie; Carmon, Kendra S; Reiner, Thomas; Schonbrunn, Agnes; Azhdarinia, Ali

    2017-07-13

    Fluorescently labeled imaging agents can identify surgical margins in real-time to help achieve complete resections and minimize the likelihood of local recurrence. However, photon attenuation limits fluorescence-based imaging to superficial lesions or lesions that are a few millimeters beneath the tissue surface. Contrast agents that are dual-labeled with a radionuclide and fluorescent dye can overcome this limitation and combine quantitative, whole-body nuclear imaging with intraoperative fluorescence imaging. Using a multimodality chelation (MMC) scaffold, IRDye 800CW was conjugated to the clinically used somatostatin analog, 68 Ga-DOTA-TOC, to produce the dual-labeled analog, 68 Ga-MMC(IRDye 800CW)-TOC, with high yield and specific activity. In vitro pharmacological assays demonstrated retention of receptor-targeting properties for the dual-labeled compound with robust internalization that was somatostatin receptor (SSTR) 2-mediated. Biodistribution studies in mice identified the kidneys as the primary excretion route for 68 Ga-MMC(IRDye 800CW)-TOC, along with clearance via the reticuloendothelial system. Higher uptake was observed in most tissues compared to 68 Ga-DOTA-TOC but decreased as a function of time. The combination of excellent specificity for SSTR2-expressing cells and suitable biodistribution indicate potential application of 68 Ga-MMC(IRDye 800CW)-TOC for intraoperative detection of SSTR2-expressing tumors.

  15. Long-term Primary Medical Therapy with Somatostatin Analogs in Acromegaly

    Directory of Open Access Journals (Sweden)

    Deng-Huang Su

    2006-01-01

    Full Text Available To cure acromegalic patients, transsphenoidal surgery is considered first, especially for microadenoma. However, less than 50% of patients with macroadenoma achieve satisfactory biochemical control. Moreover, surgery may cause hypopituitarism. Medical therapy may offer the prospect of near normalization of growth hormone (GH/insulin-like growth factor-1 levels with substantial tumor shrinkage in a significant number of patients. Here, we report two cases of acromegaly under treatment with somato-statin analogs alone for more than 10 years. Case 1 was a 54-year-old man with a pituitary macro-adenoma. He received 4 years of octreotide treatment followed by 6 years of prolonged-release (PR lanreotide resulting in normal GH level. Case 2 was a 60-year-old woman with a 1.3 cm pituitary tumor. She received 8 years of octreotide treatment followed by 6 years of PR lanreotide resulting in subnormal GH level and gallbladder sludge. She had received bilateral total hip replacement for hip osteoarthritis at the age of 59 years. These cases illustrate that long-term treatment with somatostatin analogs offers an alternative choice in selected acromegalic patients, such as those with pituitary tumor who cannot be cured by surgery, those who have unacceptable anesthetic risk and those who refuse surgery.

  16. Application of single-vial ready-for-use formulation of 111In- or 177Lu-labelled somatostatin analogs.

    Science.gov (United States)

    de Blois, Erik; Chan, Ho Sze; de Zanger, Rory; Konijnenberg, Mark; Breeman, Wouter A P

    2014-02-01

    For the sake of safety it would be desirable to store and transport the ready-for-use liquid formulation (diagnostics and therapeutics) of radiolabelled peptides. The use of ethanol, in combination with a mixture of gentisic- and ascorbic acid, has superior effects on stabilizing radiolabelled somatostatin analogs. As a consequence, (111)In- and (177)Lu-labelled somatostatin analogs can be stored and transported in a single-vial ready-for-use liquid formulation up to 7 days after radiolabelling. © 2013 Published by Elsevier Ltd.

  17. Excessive grooming induced by somatostatin or its analog SMS 201-995

    NARCIS (Netherlands)

    Wimersma Greidanus, T.B. van; Maigret, C.; Krechting, B.

    1987-01-01

    Intracerebroventricular (i.c.v.) administration of somatostatin or SMS 201-995 induces excessive grooming behavior in rats. The grooming inducing effect of somatostatin is rather weak, as doses of 300 ng or less did not result in increased total grooming scores. In contrast a dose of 10 ng SMS

  18. The utility of two somatostatin analog radiopharmaceuticals in assessment of radiologically indeterminate pulmonary lesions.

    Science.gov (United States)

    Sobic-Saranovic, Dragana P; Pavlovic, Smiljana V; Artiko, Vera M; Saranovic, Djordjije Z; Jaksic, Emilija D; Subotic, Dragan; Nagorni-Obradovic, Ljudmila; Kozarevic, Nebojsa; Petrovic, Nebojsa; Grozdic, Isidora T; Obradovic, Vladimir B

    2012-01-01

    The aim of our study was to assess diagnostic accuracy of Tc-99m depreotide and Tc-99m-EDDA/HYNIC-TOC scintigraphy for evaluation of pulmonary lesions that appeared ambiguous on computed tomography (CT). Forty-nine consecutive patients (37 men and 12 women; mean age, 60 ± 11 years) with 60 pulmonary lesions on chest radiography and CT were referred for nuclear imaging. They were prospectively allocated to undergo whole-body scintigraphy (WBS) and single photon emission computed tomography (SPECT) using either Tc-99m depreotide (26 patients, group 1) or Tc-99m-EDDA/HYNIC-TOC imaging (23 patients, group 2). Histologic findings after tissue biopsy served as a gold standard for determining diagnostic accuracy of the 2 somatostatin analogs. Visual assessment was complemented by semiquantitative analysis based on target to background ratio. Among the 32 pulmonary lesions scanned with Tc-99m depreotide, focal uptake was increased in 22 of 25 malignancies, whereas no uptake was found in 6 of 7 benign lesions (88% sensitivity, 85% specificity, and 88% accuracy) on both WBS and SPECT. Imaging of 28 pulmonary lesions with Tc-99m-EDDA/HYNIC-TOC had a similar diagnostic yield (sensitivity 87%, specificity 84%, and accuracy 86%). Overall, target to background ratios were higher on SPECT than WBS but not significantly different between groups 1 and 2 (SPECT 2.72 ± 0.70 vs. 2.71 ± 0.50, WBS 1.61 ± 0.32 vs. 1.62 ± 0.28, respectively). This study demonstrates that Tc-99m depreotide and Tc-99m-EDDA/HYNIC-TOC have similar diagnostic value for characterizing pulmonary lesions that appear ambiguous on CT.

  19. Place of preoperative treatment of acromegaly with somatostatin analog on surgical outcome: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Francisco Pita-Gutierrez

    Full Text Available CONTEXT: Transsphenoidal neurosurgery is the accepted first-line treatment of acromegaly in the majority of patients. Previous studies addressing preoperative somatostatin analog (SSA treatment and subsequent surgical cure rates are conflicting, reporting either benefits or no significant differences. OBJECTIVE: The aim of this study, based on a meta-analysis of all published reports, was to investigate whether treatment with SSA before surgery improves the surgical outcome of acromegaly. DATA SOURCES: All studies of preoperative treatment of acromegaly with SSA were systematically reviewed up to December 2011. We searched the Medline, Embase, Cochrane and Google Scholar electronic databases. STUDY SELECTION: The primary endpoint was the biochemical postoperative cure rate. We identified 286 studies, out of which 10 studies (3.49% fulfilling the eligibility criteria were selected for analysis; five retrospective studies with a control group, two prospective non-randomized trials, and three prospective controlled trials. The meta-analysis was conducted using the random-effects model. DATA EXTRACTION: Data were extracted from published reports by two independent observers. DATA SYNTHESIS: A borderline effect was detected in the analysis of all of the trials with control groups, with a pooled odds ratio (OR for biochemical cure with SSA treatment of 1.62 (95% CI, 0.93-2.82. In the analysis of the three prospective controlled trials, a statistically significant effect was identified OR: 3.62 (95% CI, 1.88-6.96. CONCLUSIONS: Preoperative treatment with SSA og GH-secreting pituitary adenomas shows a significant improvement on surgical results. This meta-analysis suggests that in centers without optimal results all patients with a GH-secreting pituitary macroadenoma should be treated with a long-acting SSA prior to surgical treatment.

  20. Budget impact of somatostatin analogs as treatment for metastatic gastroenteropancreatic neuroendocrine tumors in US hospitals

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    Ortendahl JD

    2017-08-01

    Full Text Available Jesse D Ortendahl,1 Sonia J Pulgar,2 Beloo Mirakhur,3 David Cox,3 Tanya GK Bentley,1 Alexandria T Phan4 1Health Economics, Partnership for Health, LLC, Beverly Hills, CA, USA; 2Health Economics and Outcomes Research, Ipsen Biopharmaceuticals, Basking Ridge, NJ, USA; 3Medical Affairs, Oncology, Ipsen Biopharmaceuticals, Basking Ridge, NJ, USA; 4GI Medical Oncology, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA Objective: With the introduction of new therapies, hospitals have to plan spending limited resources in a cost-effective manner. To assist in identifying the optimal treatment for patients with locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors, budget impact modeling was used to estimate the financial implications of adoption and diffusion of somatostatin analogs (SSAs. Patients and methods: A hypothetical cohort of 500 gastroenteropancreatic neuroendocrine tumor patients was assessed in an economic model, with the proportion with metastatic disease treated with an SSA estimated using published data. Drug acquisition, preparation, and administration costs were based on national pricing databases and published literature. Octreotide dosing was based on published estimates of real-world data, whereas for lanreotide, real-world dosing was unavailable and we therefore used the highest indicated dosing. Alternative scenarios reflecting the proportion of patients receiving lanreotide or octreotide were considered to estimate the incremental budget impact to the hospital. Results: In the base case, 313 of the initial 500 gastroenteropancreatic neuroendocrine tumor patients were treated with an SSA. The model-predicted per-patient cost was US$83,473 for lanreotide and US$89,673 for octreotide. With a hypothetical increase in lanreotide utilization from 5% to 30% of this population, the annual model-projected hospital costs decreased by US$488,615. When varying the inputs in one-way sensitivity

  1. Radiolabeled somatostatin analog scintigraphy in oncology and immune diseases: an overview

    International Nuclear Information System (INIS)

    Kwekkeboom, D.J.; Krenning, E.P.

    1997-01-01

    [ 111 In-DTPA-D-Phe 1 [-octreotide is a new radiopharmaceutical with a great potential for the visualization of somatostatin receptor-positive tumors, granulomas, and diseases in which activated leukocytes play a role. The overall sensitivity of [ 111 In-DTPA-D-Phe 1 [-octreotide scintigraphy to localize neuroendocrine tumors is high. In several neuroendocrine tumor types, inclusion of somatostatin receptor imaging in the localization or staging procedure may be very rewarding, either in terms of cost-effectiveness, patient management, or quality of life. In our opinion, this holds true for patients with carcinoids, gastrinomas, paragangliomas, small-cell lung carcinoma, and selected cases of patients with insulinomas. The value of [ 111 In-DTPA-D-Phe 1 [-octreotide scintigraphy in patients with other tumors, such as breast cancer, malignant lymphomas, or in patients with granulomatous diseases, has to be established. (orig.). With 4 figs., 1 tab

  2. Preclinical evaluation of somatostatin analogs bearing two macrocyclic chelators for high specific activity labeling with radiometals

    International Nuclear Information System (INIS)

    Storch, D.; Schmitt, J.S.; Waldherr, C.; Maecke, H.R.; Waser, B.; Reubi, J.C.

    2007-01-01

    Radiometallated analogues of the regulatory peptide somatostatin are of interest in the in vivo localization and targeted radiotherapy of somatostatin receptor-overexpressing tumors. An important aspect of their use in vivo is a fast and efficient labeling (complexation) protocol for radiometals along with a high specific activity. We describe in this manuscript synthetic methods for the coupling of two chelators (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid = DOTA) to the bioactive peptide [Tyr 3 ,Thr 8 ]-octreotide (TATE) in order to increase the specific activity (radioactivity in Bq per mole peptide). The full chelator-linker-peptide conjugate was assembled on solid support using standard Fmoc chemistry. Two DOTA-chelators were linked to the peptide using lysine or N,N'-bis(3-aminopropyl)-glycine (Apg); in addition, pentasarcosine (Sar 5 ) was used as a spacer between the chelators and the peptide to probe its influence on biology and pharmacology. Complexation rates with In 3+ and Y 3+ salts and the corresponding radiometals were high, the bis-DOTA-derivatives showed higher complexation rates and gave higher specific activity than DOTA-TATE. Pharmacological and biological data of the complexed molecules did not show significant differences if compared to the parent peptide [ 111/nat In-DOTA]-TATE except for [( 111/nat In-DOTA) 2 -Apg]-TATE which showed a lower binding affinity and rate of internalization into tumor cells. The biodistribution of [( 111/nat In-DOTA)-Lys( 111/nat In-DOTA)]-TATE in the rat tumor model (AR4-2J) showed a high and specific (as shown by a blocking experiment) tracer uptake in somatostatin receptor-positive tissue but a lower tumor uptake compared to [ 111/nat In-DOTA]-TATE. (orig.)

  3. Preliminary PET/CT Imaging with Somatostatin Analogs [68Ga]DOTAGA-TATE and [68Ga]DOTAGA-TOC.

    Science.gov (United States)

    Satpati, Drishty; Shinto, Ajit; Kamaleshwaran, K K; Sarma, Haladhar Dev; Dash, Ashutosh

    2017-12-01

    Somatostatin receptor positron emission tomography/X-ray computed tomography (SSTR-PET/CT) is a well-established technique for staging and detection of neuroendocrine tumors (NETs). Ga-68-labeled DOTA-conjugated octreotide analogs are the privileged radiotracers for diagnosis and therapeutic monitoring of NETs. Hence, we were interested in assessing the influence of promising, newer variant DOTAGA on the hydrophilicity, pharmacokinetics, and lesion pick-up of somatostatin analogs. Herein, the potential of ([ 68 Ga]DOTAGA, Tyr 3 , Thr 8 ) octreotide ([ 68 Ga]DOTAGA-TATE) and ([ 68 Ga]DOTAGA, Tyr 3 ) octreotide ([ 68 Ga]DOTAGA-TOC) as NET imaging agents has been investigated. Amenability of [ 68 Ga]DOTAGA-(TATE/TOC) to kit-type formulation has been demonstrated. Biodistribution studies were carried out in normal rats at 1 h post-injection (p.i.). [ 68 Ga]DOTAGA-(TATE/TOC) PET/CT scans were carried out in patients (70-170 MBq, 1 h p.i.) with histologically confirmed well-differentiated NETs. [ 68 Ga]DOTAGA-TATE exhibited hydrophilicity similar to [ 68 Ga]DOTA-TATE (log P = -3.51 vs -3.69) whereas [ 68 Ga]DOTAGA-TOC was more hydrophilic than [ 68 Ga]DOTA-TOC (log P = -3.27 vs -2.93). [ 68 Ga]DOTAGA-TATE and [ 68 Ga]DOTA-TATE showed almost identical blood and kidney uptake in normal rats whereas significantly fast clearance (p TOC also demonstrated rapid clearance from blood and kidneys (p TOC. The metastatic lesions in NET patients were well identified by [ 68 Ga]DOTAGA-TATE and [ 68 Ga]DOTAGA-TOC. The phenomenal analogy was observed between [ 68 Ga]DOTAGA-TATE and [ 68 Ga]DOTA-TATE as well as between [ 68 Ga]DOTAGA-TOC and [ 68 Ga]DOTA-TOC in biodistribution studies in rats. The good lesion detection ability of the two radiotracers indicates their potential as NET imaging radiotracers.

  4. Predictive value of T2 relative signal intensity for response to somatostatin analogs in newly diagnosed acromegaly

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Ming; Zhang, Qilin [Fudan University, Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Shanghai (China); Shanghai Pituitary Tumor Center, Shanghai (China); Liu, Wenjuan; Li, Yiming; Zhang, Zhaoyun; Ye, Hongying; He, Min; Lu, Bin; Yang, Yeping [Shanghai Pituitary Tumor Center, Shanghai (China); Fudan University, Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Shanghai (China); Wang, Meng [Fudan University, Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Shanghai (China); Soochow University, Division of Endocrinology, the Second Affiliated Hospital, Suzhou (China); Zhu, Jingjing [Shanghai Pituitary Tumor Center, Shanghai (China); Fudan University, Department of Neuropathology, Huashan Hospital, Shanghai Medical College, Shanghai (China); Ma, Zengyi; He, Wenqiang; Li, Shiqi; Shou, Xuefei; Qiao, Nidan; Ye, Zhao; Zhang, Yichao; Zhao, Yao; Wang, Yongfei [Fudan University, Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Shanghai (China); Shanghai Pituitary Tumor Center, Shanghai (China); Yao, Zhenwei [Shanghai Pituitary Tumor Center, Shanghai (China); Fudan University, Department of Radiology, Huashan Hospital, Shanghai Medical College, Shanghai (China); Lu, Yun [Fudan University, Department of Nuclear Medicine, Huashan Hospital, Shanghai Medical College, Shanghai (China)

    2016-11-15

    The difficulty of predicting the efficacy of somatostatin analogs (SSA) is not fully resolved. Here, we quantitatively evaluated the predictive value of relative signal intensity (rSI) on T1- and T2-weighted magnetic resonance imaging (MRI) for the short-term efficacy (3 months) of SSA therapy in patients with active acromegaly and assessed the correlation between MRI rSI and expression of somatostatin receptors (SSTR). This was a retrospective review of prospectively recorded data. Ninety-two newly diagnosed patients (37 males and 55 females) with active acromegaly were recruited. All patients were treated with pre-surgical SSA, followed by reassessment and transspenoidal surgery. rSI values were generated by calculating the ratio of SI in the tumor to the SI of normal frontal white matter. The Youden indices were calculated to determine the optimal cutoff of rSI to determine the efficacy of SSA. The correlation between rSI and expression of SSTR2/5 was analyzed by the Spearman rank correlation coefficient. T2 rSI was strongly correlated with biochemical sensitivity to SSA. The cutoff value of T2 rSI to distinguish biochemical sensitivity was 1.205, with a positive predictive value (PPV) of 81.5 % and a negative predictive value (NPV) of 77.3 %. No correlation was found between MRI and tumor size sensitivity. Moreover, T2 rSI was negatively correlated with the expression of SSTR5. T2 rSI correlates with the expression of SSTR5 and quantitatively predicts the biochemical efficacy of SSA in acromegaly. (orig.)

  5. Predictive value of T2 relative signal intensity for response to somatostatin analogs in newly diagnosed acromegaly

    International Nuclear Information System (INIS)

    Shen, Ming; Zhang, Qilin; Liu, Wenjuan; Li, Yiming; Zhang, Zhaoyun; Ye, Hongying; He, Min; Lu, Bin; Yang, Yeping; Wang, Meng; Zhu, Jingjing; Ma, Zengyi; He, Wenqiang; Li, Shiqi; Shou, Xuefei; Qiao, Nidan; Ye, Zhao; Zhang, Yichao; Zhao, Yao; Wang, Yongfei; Yao, Zhenwei; Lu, Yun

    2016-01-01

    The difficulty of predicting the efficacy of somatostatin analogs (SSA) is not fully resolved. Here, we quantitatively evaluated the predictive value of relative signal intensity (rSI) on T1- and T2-weighted magnetic resonance imaging (MRI) for the short-term efficacy (3 months) of SSA therapy in patients with active acromegaly and assessed the correlation between MRI rSI and expression of somatostatin receptors (SSTR). This was a retrospective review of prospectively recorded data. Ninety-two newly diagnosed patients (37 males and 55 females) with active acromegaly were recruited. All patients were treated with pre-surgical SSA, followed by reassessment and transspenoidal surgery. rSI values were generated by calculating the ratio of SI in the tumor to the SI of normal frontal white matter. The Youden indices were calculated to determine the optimal cutoff of rSI to determine the efficacy of SSA. The correlation between rSI and expression of SSTR2/5 was analyzed by the Spearman rank correlation coefficient. T2 rSI was strongly correlated with biochemical sensitivity to SSA. The cutoff value of T2 rSI to distinguish biochemical sensitivity was 1.205, with a positive predictive value (PPV) of 81.5 % and a negative predictive value (NPV) of 77.3 %. No correlation was found between MRI and tumor size sensitivity. Moreover, T2 rSI was negatively correlated with the expression of SSTR5. T2 rSI correlates with the expression of SSTR5 and quantitatively predicts the biochemical efficacy of SSA in acromegaly. (orig.)

  6. Predictive value of T2 relative signal intensity for response to somatostatin analogs in newly diagnosed acromegaly.

    Science.gov (United States)

    Shen, Ming; Zhang, Qilin; Liu, Wenjuan; Wang, Meng; Zhu, Jingjing; Ma, Zengyi; He, Wenqiang; Li, Shiqi; Shou, Xuefei; Li, Yiming; Zhang, Zhaoyun; Ye, Hongying; He, Min; Lu, Bin; Yao, Zhenwei; Lu, Yun; Qiao, Nidan; Ye, Zhao; Zhang, Yichao; Yang, Yeping; Zhao, Yao; Wang, Yongfei

    2016-11-01

    The difficulty of predicting the efficacy of somatostatin analogs (SSA) is not fully resolved. Here, we quantitatively evaluated the predictive value of relative signal intensity (rSI) on T1- and T2-weighted magnetic resonance imaging (MRI) for the short-term efficacy (3 months) of SSA therapy in patients with active acromegaly and assessed the correlation between MRI rSI and expression of somatostatin receptors (SSTR). This was a retrospective review of prospectively recorded data. Ninety-two newly diagnosed patients (37 males and 55 females) with active acromegaly were recruited. All patients were treated with pre-surgical SSA, followed by reassessment and transspenoidal surgery. rSI values were generated by calculating the ratio of SI in the tumor to the SI of normal frontal white matter. The Youden indices were calculated to determine the optimal cutoff of rSI to determine the efficacy of SSA. The correlation between rSI and expression of SSTR2/5 was analyzed by the Spearman rank correlation coefficient. T2 rSI was strongly correlated with biochemical sensitivity to SSA. The cutoff value of T2 rSI to distinguish biochemical sensitivity was 1.205, with a positive predictive value (PPV) of 81.5 % and a negative predictive value (NPV) of 77.3 %. No correlation was found between MRI and tumor size sensitivity. Moreover, T2 rSI was negatively correlated with the expression of SSTR5. T2 rSI correlates with the expression of SSTR5 and quantitatively predicts the biochemical efficacy of SSA in acromegaly.

  7. In vivo detection of somatostatin receptors in patients with functionless pituitary adenomas by means of a radioiodinated analog of somatostatin ((123I)SDZ 204-090)

    Energy Technology Data Exchange (ETDEWEB)

    Faglia, G.; Bazzoni, N.; Spada, A.; Arosio, M.; Ambrosi, B.; Spinelli, F.; Sara, R.; Bonino, C.; Lunghi, F. (Institute of Endocrine Sciences, University of Milan, Ospedale Maggiore IRCCS (Italy))

    1991-10-01

    The recent availability of a Tyr3-substituted octreotide (SDZ 204-090) for radioiodination has allowed somatostatin (SRIH) receptor binding to be studied in vivo, and receptor-positive tumors of different origins to be visualized with a gamma-camera. This prompted us to investigate whether this compound could be used for external imaging of functionless pituitary adenomas displaying SRIH receptors. Eight patients with functionless pituitary adenomas, three patients with acromegaly, and three with macroprolactinoma were injected iv with 123I-labeled Tyr3-octreotide and then scanned with a gamma-camera. Positive scans were obtained in the three acromegalics and in two of the eight patients with functionless pituitary tumors. The patients with macroprolactinoma had negative scans. The diagnosis of functionless pituitary adenomas was confirmed by light and electron microscopic examination as well as immunocytochemical studies. In vitro binding of (125I)Tyr11-SRIH to cell membranes was evaluated in four functionless and three GH-secreting adenomas removed from seven of the patients. All of the GH-secreting as well as one of the four functionless adenomas had high affinity SRIH-binding sites, without differences in number or affinity, whereas SRIH-binding sites were not detected in the others. Positive scans were observed only in patients bearing tumors with high affinity SRIH-binding sites. In conclusion, (123I)Tyr3-octreotide appears to be a promising tool for singling out, in vivo, patients with functionless pituitary tumors displaying SRIH receptors who might potentially benefit from octreotide treatment.

  8. Radioautographic localization of somatostatin-14 and somatostatin-28 binding sites in the rat brain

    International Nuclear Information System (INIS)

    Leroux, P.; Pelletier, G.

    1984-01-01

    Somatostatin-14 (S14) and its precursor, somatostatin-28 (S28), are widely distributed throughout the rat brain, suggesting that they could act as neurotransmitter or neuromodulator in the central nervous system. The present study was undertaken to study the localization of S14 and S28 receptors in the rat brain determined by ''in vitro'' radioautography. The study performed on slide mounted frozen brain section with iodinated S14 and S28 analogs revealed an identical distribution of binding sites for the two forms of somatostatin. A good correlation could be observed between receptor distribution and immunohistologically localized neuropeptides except for striatum and hypothalamus. However, receptors were not detectable in the hypothalamus and were found in low concentration in the caudate-putamen nucleus, two regions containing high amounts of S28 and S14, suggesting a high occupancy of receptors in these areas by endogenous peptides or an inverse correlation between receptor and peptide concentrations

  9. Delayed release formulation of the somatostatin analog RC-160 inhibits the growth hormone (GH) response to GH-releasing factor-(1-29)NH2 and decreases elevated prolactin levels in rats.

    Science.gov (United States)

    Bokser, L; Schally, A V

    1988-10-01

    Recently, we have developed a long-acting delivery system for our somatostatin (SS) analog RC-160 based on injectable microcapsules in poly-(D,L-lactide-coglycolide). We studied the capacity of this formulation to repeatedly block the GH secretion induced by administration of GRF-(1-29)NH2 (GRF) on different days. Male rats anesthetized with pentobarbital were injected iv with 2.5 micrograms/kg BW GRF-(1-29)NH2 or saline. Five minutes later, blood samples were taken for GH measurement, and the animals were injected im with RC-160 microcapsules at a dose calculated to release 25 micrograms/day of the analog for 7 days or with the vehicle. The GRF stimuli were repeated 48 h, 96 h, and 8 days after administration of SS analog in microcapsules. GRF administration increased GH levels at the four times tested (P less than 0.01) in the control group injected with vehicle, while RC-160 microcapsules inhibited the GH response for more than 96 h (P less than 0.01). The GH levels augmented by pentobarbital were also decreased by the RC-160 microcapsules (P less than 0.01). Animals treated with microcapsules showed smaller increases in their body weight than untreated rats (P less than 0.05). We also investigated the effect of RC-160 microcapsules on hyperprolactinemic female rats implanted with pituitary glands under the kidney capsules. High PRL levels in rats bearing pituitary grafts showed a significant decrease when measured 4 days after the administration of RC-160 microcapsules. These results demonstrate the efficacy of the long-acting delivery system of the SS analog RC-160 and suggest the possible clinical usefulness of this formulation for lowering GH and PRL levels.

  10. Relative potencies of the somatostatin analogs octreotide, BIM-23014, and RC-160 on the inhibition of hormone release by cultured human endocrine tumor cells and normal rat anterior pituitary cells

    NARCIS (Netherlands)

    L.J. Hofland (Leo); P.M. van Koetsveld (Peter); M. Waaijers (Marlijn); J. Zuyderwijk; S.W.J. Lamberts (Steven)

    1994-01-01

    textabstractIn the present study we investigated the effects of the somatostatin (SS) analogs octreotide, RC-160, and BIM-23014 on GH release by cultured cells of human GH-secreting pituitary tumors, in normal rat anterior pituitary cells, and on gastrin release by

  11. Hepatic Cyst Infection During Use of the Somatostatin Analog Lanreotide in Autosomal Dominant Polycystic Kidney Disease: An Interim Analysis of the Randomized Open-Label Multicenter DIPAK-1 Study

    NARCIS (Netherlands)

    Lantinga, M.A. (Marten A.); D’Agnolo, H.M.A. (Hedwig M. A.); E. Casteleijn (Eric); de Fijter, J.W. (Johan W.); E. Meijer (Esther); A.L. Messchendorp (A. Lianne); D. Peters (Dorien); M. Salih (Mahdi); E.M. Spithoven (Edwin); D. Soonawala (Darius); F.W. Visser (Folkert); Wetzels, J.F.M. (Jack F. M.); R. Zietse (Bob); J.P.H. Drenth (Joost); R.T. Gansevoort (Ron); Drenth, J.P.H.; J.W. de Fijter (Johan); Gansevoort, R.T.; D.J.M. Peters (Dorien J.M.); J.F.M. Wetzels (Jack); Zietse, R.

    2017-01-01

    textabstractIntroduction and Aims: The DIPAK-1 Study investigates the reno- and hepatoprotective efficacy of the somatostatin analog lanreotide compared with standard care in patients with later stage autosomal dominant polycystic kidney disease (ADPKD). During this trial, we witnessed several

  12. A clinical and radiological objective tumor response with somatostatin analogs (SSA in well-differentiated neuroendocrine metastatic tumor of the ileum: a case report

    Directory of Open Access Journals (Sweden)

    De Divitiis C

    2015-03-01

    Full Text Available Chiara De Divitiis,1 Claudia von Arx,2 Roberto Carbone,3 Fabiana Tatangelo,4 Elena di Girolamo,5 Giovanni Maria Romano,1 Alessandro Ottaiano,1 Elisabetta de Lutio di Castelguidone,3 Rosario Vincenzo Iaffaioli,1 Salvatore Tafuto1 On behalf of the European Neuroendocrine Tumor Society (ENETS Center of Excellence Multidisciplinary Group for Neuroendocrine Tumors in Naples (Italy 1Department of Abdominal Oncology, National Cancer Institute “Fondazione G. Pascale”, Naples, Italy; 2Department of Clinical Medicine and Surgery, “Federico II” University, Naples, Italy; 3Department of Radiology, 4Department of Pathology, 5Department of Endoscopy, National Cancer Institute “Fondazione G Pascale”, Naples, Italy Abstract: Somatostatin analogs (SSAs are typically used to treat the symptoms caused by neuroendocrine tumors (NETs, but they are not used as the primary treatment to induce tumor shrinkage. We report a case of a 63-year-old woman with a symptomatic metastatic NET of the ileum. Complete symptomatic response was achieved after 1 month of treatment with SSAs. In addition, there was an objective response in the liver, with the disappearance of secondary lesions noted on computed tomography scan after 3 months of octreotide treatment. Our experience suggests that SSAs could be useful for downstaging and/or downsizing well-differentiated NETs, and they could allow surgery to be performed. Such presurgery therapy could be a promising tool in the management of patients with initially inoperable NETs. Keywords: neuroendocrine tumor, somatostatin analogs, octreotide, metastatic tumor of the ileum, radiological tumor response

  13. Gene transcript analysis blood values correlate with {sup 68}Ga-DOTA-somatostatin analog (SSA) PET/CT imaging in neuroendocrine tumors and can define disease status

    Energy Technology Data Exchange (ETDEWEB)

    Bodei, L. [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Kidd, M.; Modlin, I.M.; Drozdov, I. [Wren Laboratories, Branford, CT (United States); Prasad, V. [Charite University Hospital, Department of Nuclear Medicine, Berlin (Germany); Severi, S.; Paganelli, G. [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine and Radiometabolic Units, Meldola (Italy); Ambrosini, V. [S. Orsola-Malpighi University Hospital, Nuclear Medicine, Bologna (Italy); Kwekkeboom, D.J.; Krenning, E.P. [Erasmus Medical Center Rotterdam, Nuclear Medicine Department, Rotterdam (Netherlands); Baum, R.P. [Zentralklinik Bad Berka, THERANOSTICS Center for Molecular Radiotherapy and Imaging, Bad Berka (Germany)

    2015-08-15

    Precise determination of neuroendocrine tumor (NET) disease status and response to therapy remains a rate-limiting concern for disease management. This reflects limitations in biomarker specificity and resolution capacity of imaging. In order to evaluate biomarker precision and identify if combinatorial blood molecular markers and imaging could provide added diagnostic value, we assessed the concordance between {sup 68}Ga-somatostatin analog (SSA) positron emission tomography (PET), circulating NET gene transcripts (NETest), chromogranin A (CgA), and Ki-67 in NETs. We utilized two independent patient groups with positive {sup 68}Ga-SSA PET: data set 1 ({sup 68}Ga-SSA PETs undertaken for peptide receptor radionuclide therapy (PRRT), as primary or salvage treatment, n = 27) and data set 2 ({sup 68}Ga-SSA PETs performed in patients referred for initial disease staging or restaging after various therapies, n = 22). We examined the maximum standardized uptake value (SUV{sub max}), circulating gene transcripts, CgA levels, and baseline Ki-67. Regression analyses, generalized linear modeling, and receiver-operating characteristic (ROC) analyses were undertaken to determine the strength of the relationships. SUV{sub max} measured in two centers were mathematically evaluated (regression modeling) and determined to be comparable. Of 49 patients, 47 (96 %) exhibited a positive NETest. Twenty-six (54 %) had elevated CgA (χ{sup 2} = 20.1, p < 2.5 x 10{sup -6}). The majority (78 %) had Ki-67 < 20 %. Gene transcript scores were predictive of imaging with >95 % concordance and significantly correlated with SUV{sub max} (R {sup 2} = 0.31, root-mean-square error = 9.4). The genes MORF4L2 and somatostatin receptors SSTR1, 3, and 5 exhibited the highest correlation with SUV{sub max}. Progressive disease was identified by elevated levels of a quotient of MORF4L2 expression and SUV{sub max} [ROC-derived AUC (R {sup 2} = 0.7, p < 0.05)]. No statistical relationship was identified

  14. Gene transcript analysis blood values correlate with 68Ga-DOTA-somatostatin analog (SSA) PET/CT imaging in neuroendocrine tumors and can define disease status

    International Nuclear Information System (INIS)

    Bodei, L.; Kidd, M.; Modlin, I.M.; Drozdov, I.; Prasad, V.; Severi, S.; Paganelli, G.; Ambrosini, V.; Kwekkeboom, D.J.; Krenning, E.P.; Baum, R.P.

    2015-01-01

    Precise determination of neuroendocrine tumor (NET) disease status and response to therapy remains a rate-limiting concern for disease management. This reflects limitations in biomarker specificity and resolution capacity of imaging. In order to evaluate biomarker precision and identify if combinatorial blood molecular markers and imaging could provide added diagnostic value, we assessed the concordance between 68 Ga-somatostatin analog (SSA) positron emission tomography (PET), circulating NET gene transcripts (NETest), chromogranin A (CgA), and Ki-67 in NETs. We utilized two independent patient groups with positive 68 Ga-SSA PET: data set 1 ( 68 Ga-SSA PETs undertaken for peptide receptor radionuclide therapy (PRRT), as primary or salvage treatment, n = 27) and data set 2 ( 68 Ga-SSA PETs performed in patients referred for initial disease staging or restaging after various therapies, n = 22). We examined the maximum standardized uptake value (SUV max ), circulating gene transcripts, CgA levels, and baseline Ki-67. Regression analyses, generalized linear modeling, and receiver-operating characteristic (ROC) analyses were undertaken to determine the strength of the relationships. SUV max measured in two centers were mathematically evaluated (regression modeling) and determined to be comparable. Of 49 patients, 47 (96 %) exhibited a positive NETest. Twenty-six (54 %) had elevated CgA (χ 2 = 20.1, p < 2.5 x 10 -6 ). The majority (78 %) had Ki-67 < 20 %. Gene transcript scores were predictive of imaging with >95 % concordance and significantly correlated with SUV max (R 2 = 0.31, root-mean-square error = 9.4). The genes MORF4L2 and somatostatin receptors SSTR1, 3, and 5 exhibited the highest correlation with SUV max . Progressive disease was identified by elevated levels of a quotient of MORF4L2 expression and SUV max [ROC-derived AUC (R 2 = 0.7, p < 0.05)]. No statistical relationship was identified between CgA and Ki-67 and no relationship with imaging parameters

  15. Evaluation of somatostatin and nucleolin receptors for therapeutic delivery in non-small cell lung cancer stem cells applying the somatostatin-analog DOTATATE and the nucleolin-targeting aptamer AS1411.

    Directory of Open Access Journals (Sweden)

    Sif Holmboe

    Full Text Available Cancer stem cells represent the putative tumor-driving subpopulation thought to account for drug resistance, relapse, and metastatic spread of epithelial and other cancer types. Accordingly, cell surface markers for therapeutic delivery to cancer stem cells are subject of intense research. Somatostatin receptor 2 and nucleolin are known to be overexpressed by various cancer types, which have elicited comprehensive efforts to explore their therapeutic utilization. Here, we evaluated somatostatin receptor 2 targeting and nucleolin targeting for therapeutic delivery to cancer stem cells from lung cancer. Nucleolin is expressed highly but not selectively, while somatostatin receptor 2 is expressed selectively but not highly by cancer cells. The non-small cell lung cancer cell lines A549 and H1299, displayed average levels of both surface molecules as judged based on analysis of a larger cell line panel. H1299 compared to A549 cells showed significantly elevated sphere-forming capacity, indicating higher cancer stem cell content, thus qualifying as suitable test system. Nucleolin-targeting 57Co-DOTA-AS1411 aptamer showed efficient internalization by cancer cells and, remarkably, at even higher efficiency by cancer stem cells. In contrast, somatostatin receptor 2 expression levels were not sufficiently high in H1299 cells to confer efficient uptake by either non-cancer stem cells or cancer stem cells. The data provides indication that the nucleolin-targeting AS1411 aptamer might be used for therapeutic delivery to non-small cell lung cancer stem cells.

  16. Parvalbumin-expressing interneurons can act solo while somatostatin-expressing interneurons act in chorus in most cases on cortical pyramidal cells.

    Science.gov (United States)

    Safari, Mir-Shahram; Mirnajafi-Zadeh, Javad; Hioki, Hiroyuki; Tsumoto, Tadaharu

    2017-10-06

    Neural circuits in the cerebral cortex consist primarily of excitatory pyramidal (Pyr) cells and inhibitory interneurons. Interneurons are divided into several subtypes, in which the two major groups are those expressing parvalbumin (PV) or somatostatin (SOM). These subtypes of interneurons are reported to play distinct roles in tuning and/or gain of visual response of pyramidal cells in the visual cortex. It remains unclear whether there is any quantitative and functional difference between the PV → Pyr and SOM → Pyr connections. We compared unitary inhibitory postsynaptic currents (uIPSCs) evoked by electrophysiological activation of single presynaptic interneurons with population IPSCs evoked by photo-activation of a mass of interneurons in vivo and in vitro in transgenic mice in which PV or SOM neurons expressed channelrhodopsin-2, and found that at least about 14 PV neurons made strong connections with a postsynaptic Pyr cell while a much larger number of SOM neurons made weak connections. Activation or suppression of single PV neurons modified visual responses of postsynaptic Pyr cells in 6 of 7 pairs whereas that of single SOM neurons showed no significant modification in 8 of 11 pairs, suggesting that PV neurons can act solo whereas most of SOM neurons may act in chorus on Pyr cells.

  17. Osilodrostat (LCI699), a potent 11β-hydroxylase inhibitor, administered in combination with the multireceptor-targeted somatostatin analog pasireotide: A 13-week study in rats

    Energy Technology Data Exchange (ETDEWEB)

    Li, Li, E-mail: li1.li@novartis.com [Preclinical Safety, Novartis Institutes for BioMedical Research, East Hanover, NJ (United States); Vashisht, Kapil; Boisclair, Julie [Preclinical Safety, Novartis Institutes for BioMedical Research, East Hanover, NJ (United States); Li, Wenkui; Lin, Tsu-han [Drug Metabolism and Pharmacokinetics, Novartis Institutes for BioMedical Research, East Hanover, NJ (United States); Schmid, Herbert A. [Novartis Oncology Development, Basel (Switzerland); Kluwe, William; Schoenfeld, Heidi; Hoffmann, Peter [Preclinical Safety, Novartis Institutes for BioMedical Research, East Hanover, NJ (United States)

    2015-08-01

    The somatostatin analog pasireotide and the 11β-hydroxylase inhibitor osilodrostat (LCI699) reduce cortisol levels by distinct mechanisms of action. There exists a scientific rationale to investigate the clinical efficacy of these two agents in combination. This manuscript reports the results of a toxicology study in rats, evaluating different doses of osilodrostat and pasireotide alone and in combination. Sixty male and 60 female rats were randomized into single-sex groups to receive daily doses of pasireotide (0.3 mg/kg/day, subcutaneously), osilodrostat (20 mg/kg/day, orally), osilodrostat/pasireotide in combination (low dose, 1.5/0.03 mg/kg/day; mid-dose, 5/0.1 mg/kg/day; or high dose, 20/0.3 mg/kg/day), or vehicle for 13 weeks. Mean body-weight gains from baseline to Week 13 were significantly lower in the pasireotide-alone and combined-treatment groups compared to controls, and were significantly higher in female rats receiving osilodrostat monotherapy. Osilodrostat and pasireotide monotherapies were associated with significant changes in the histology and mean weights of the pituitary and adrenal glands, liver, and ovary/oviduct. Osilodrostat alone was associated with adrenocortical hypertrophy and hepatocellular hypertrophy. In combination, osilodrostat/pasireotide did not exacerbate any target organ changes and ameliorated the liver and adrenal gland changes observed with monotherapy. C{sub max} and AUC{sub 0–24h} of osilodrostat and pasireotide increased in an approximately dose-proportional manner. In conclusion, the pasireotide and osilodrostat combination did not exacerbate changes in target organ weight or toxicity compared with either monotherapy, and had an acceptable safety profile; addition of pasireotide to the osilodrostat regimen may attenuate potential adrenal gland hyperactivation and hepatocellular hypertrophy, which are potential side effects of osilodrostat monotherapy. - Highlights: • We examined the target organ toxicity of SOM230

  18. Effects of the single and combined treatment with dopamine agonist, somatostatin analog and mTOR inhibitors in a human lung carcinoid cell line: an in vitro study.

    Science.gov (United States)

    Pivonello, Claudia; Rousaki, Panagoula; Negri, Mariarosaria; Sarnataro, Maddalena; Napolitano, Maria; Marino, Federica Zito; Patalano, Roberta; De Martino, Maria Cristina; Sciammarella, Concetta; Faggiano, Antongiulio; Rocco, Gaetano; Franco, Renato; Kaltsas, Gregory A; Colao, Annamaria; Pivonello, Rosario

    2017-06-01

    Somatostatin analogues and mTOR inhibitors have been used as medical therapy in lung carcinoids with variable results. No data are available on dopamine agonists as treatment for lung carcinoids. The main aim of the current study was to evaluate the effect of the combined treatment of somatostatin analogue octreotide and the dopamine agonist cabergoline with mTOR inhibitors in an in vitro model of typical lung carcinoids: the NCI-H727 cell line. In NCI-H727 cell line, reverse transcriptase-quantitative polymerase chain reaction and immunofluorescence were assessed to characterize the expression of the somatostatin receptor 2 and 5, dopamine receptor 2 and mTOR pathway components. Fifteen typical lung carcinoids tissue samples have been used for somatostatin receptor 2, dopamine receptor 2, and the main mTOR pathway component p70S6K expression and localization by immunohistochemistry. Cell viability, fluorescence-activated cell sorting analysis and western blot have been assessed to test the pharmacological effects of octreotide, cabergoline and mTOR inhibitors, and to evaluate the activation of specific cell signaling pathways in NCI-H727 cell line. NCI-H727 cell line expressed somatostatin receptor 2, somatostatin receptor 5 and dopamine receptor 2 and all mTOR pathway components at messenger and protein levels. Somatostatin receptor 2, dopamine receptor 2, and p70S6K (non phosphorylated and phosphorylated) proteins were expressed in most typical lung carcinoids tissue samples. Octreotide and cabergoline did not reduce cell viability as single agents but, when combined with mTOR inhibitors, they potentiate mTOR inhibitors effect after long-term exposure, reducing Akt and ERK phosphorylation, mTOR escape mechanisms, and increasing the expression DNA-damage-inducible transcript 4, an mTOR suppressor. In conclusion, the single use of octreotide and cabergoline is not sufficient to block cell viability but the combined approach of these agents with mTOR inhibitors

  19. Functional somatostatin receptors on a rat pancreatic acinar cell line

    International Nuclear Information System (INIS)

    Viguerie, N.; Tahiri-Jouti, N.; Esteve, J.P.; Clerc, P.; Logsdon, C.; Svoboda, M.; Susini, C.; Vaysse, N.; Ribet, A.

    1988-01-01

    Somatostatin receptors from a rat pancreatic acinar cell line, AR4-2J, were characterized biochemically, structurally, and functionally. Binding of 125 I-[Tyr 11 ]Somatostatin to AR4-2J cells was saturable, exhibiting a single class of high-affinity binding sites with a maximal binding capacity of 258 ± 20 fmol/10 6 cells. Somatostatin receptor structure was analyzed by covalently cross-linking 125 I-[Tyr 11 ]somatostatin to its plasma membrane receptors. Gel electrophoresis and autoradiography of cross-linked proteins revealed a peptide containing the somatostatin receptor. Somatostatin inhibited vasoactive intestinal peptide (VIP)-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) formation in a dose-dependent manner. The concentration of somatostatin that caused half-maximal inhibition of cAMP formation was close to the receptor affinity for somatostatin. Pertussis toxin pretreatment of AR4-2J cells prevented somatostatin inhibition of VIP-stimulated cAMP formation as well as somatostatin binding. The authors conclude that AR4-2J cells exhibit functional somatostatin receptors that retain both specificity and affinity of the pancreatic acinar cell somatostatin receptors and act via the pertussis toxin-sensitive guanine nucleotide-binding protein N i to inhibit adenylate cyclase

  20. Peptide receptor radionuclide therapy of Merkel cell carcinoma using 177lutetium-labeled somatostatin analogs in combination with radiosensitizing chemotherapy. A potential novel treatment based on molecular pathology

    International Nuclear Information System (INIS)

    Salavati, A.; Prasad, V.; Baum, R.P.; Schneider, C.P.; Herbst, R.

    2012-01-01

    Few studies have been published on the safety and feasibility of synchronous use of peptide receptor radionuclide therapy (PRRNT), as source of internal radiation therapy, in combination with chemotherapy. In this study we reported a 53-year-old man with stage IV Merkel cell carcinoma (MCC), who underwent synchronous internal radiation therapy and chemotherapy. Based on presumable poor prognosis with chemotherapy only, functional similarities of MCC with other neuroendocrine tumors and available evidence of effectiveness and safety of synchronous use of external beam radiation therapy and chemotherapy in treatment of high-risk MCC patients, our interdisciplinary neuroendocrine tumor board recommended him to add PRRNT to his ongoing chemotherapy. He received 2 courses of 177 Lu-DOTATATE(1, 4, 7, 10-Tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid-1-D-Phe1-Tyr3-Thr8-octreotide) in combination with ongoing 8 cycles of liposomal doxorubicin based on standard protocols. Response to therapy was evaluated by 18 F-fluorodeoxyglucose ( 18 F-FDG) and 68 gallium-somatostatin-receptor PET/CT. There was an impressive improvement of the clinical symptoms. However, follow-up positron emission tomography (PET)/CT studies showed mixed pattern of response. Synchronous use of PRRNT and radiosensitizing chemotherapy seems safe and feasible in high risk MCC patients, however, further prospective studies and clinical trials are warranted to provide reliable evidence of possible pitfalls and effectiveness of PRRNT and 68 Ga-somatostatin-receptor PET/CT in the management of MCC. (author)

  1. Safety, Pharmacokinetics and Dosimetry of a Long-Acting Radiolabeled Somatostatin Analogue 177Lu-DOTA-EB-TATE in Patients with Advanced Metastatic Neuroendocrine Tumors.

    Science.gov (United States)

    Zhang, Jingjing; Wang, Hao; Jacobson Weiss, Orit; Cheng, Yuejuan; Niu, Gang; Li, Fang; Bai, Chunmei; Zhu, Zhaohui; Chen, Xiaoyuan

    2018-04-13

    Radiolabeled somatostatin analogue therapy has become an established treatment method for patients with well to moderately differentiated unresectable or metastatic neuroendocrine tumors (NETs). The most frequently used somatostatin analogues in clinical practice are octreotide and octreotate. However, both peptides showed suboptimal retention within tumors. The aim of this first-in-human study is to explore the safety and dosimetry of a long-acting radiolabeled somatostatin analogue, lutetium-177-1, 4, 7, 10-tetra-azacyclododecane-1, 4, 7, 10-tetraacetic acid-Evans blue-octreotate ( 177 Lu-DOTA-EB-TATE). Methods: Eight patients (6 males and 2 females; age range, 27-61 y) with advanced metastatic neuroendocrine tumors were recruited. Five patients received a single dose 0.35-0.70 GBq (9.5-18.9 mCi) of 177 Lu-DOTA-EB-TATE and underwent serial whole body planar and single-photon emission computed tomography-computed tomography (SPECT-CT) scans at 2, 24, 72, 120 and 168 h after injection. The other 3 patients received intravenous injection of 0.28-0.41 GBq (7.5-11.1 mCi) of 177 Lu-DOTATATE for the same imaging acquisition procedures at 1, 3, 4, 24 and 72 h after injection. The dosimetry was calculated using the OLINDA/EXM 1.1 software. Results: Administration of 177 Lu-DOTA-EB-TATE was well tolerated, with no adverse symptoms being noticed or reported in any of the patients. Compared with 177 Lu-DOTATATE, 177 Lu-DOTA-EB-TATE showed extended circulation in the blood and achieved 7.9-fold increase of tumor dose delivery. The total body effective doses were 0.205 ± 0.161 mSv/MBq for 177 Lu-DOTA-EB-TATE and 0.174 ± 0.072 mSv/MBq for 177 Lu-DOTATATE. Significant dose delivery increases to the kidneys and bone marrow were also observed in patients receiving 177 Lu-DOTA-EB-TATE than those receiving 177 Lu-DOTATATE (3.2 and 18.2-fold, respectively). Conclusion: By introducing an albumin binding moiety, 177 Lu-DOTA-EB-TATE showed remarkably higher uptake and retention in NET

  2. Polyunsaturated fatty acid analogs act antiarrhythmically on the cardiac IKs channel

    DEFF Research Database (Denmark)

    Liin, Sara I.; Silverå Ejneby, Malin; Barro-Soria, Rene

    2015-01-01

    Polyunsaturated fatty acids (PUFAs) affect cardiac excitability. Kv7.1 and the β-subunit KCNE1 form the cardiac IKs channel that is central for cardiac repolarization. In this study, we explore the prospects of PUFAs as IKs channel modulators. We report that PUFAs open Kv7.1 via an electrostatic...... charge at neutral pH, restore the sensitivity to open IKs channels. PUFA analogs with a positively charged head group inhibit IKs channels. These different PUFA analogs could be developed into drugs to treat cardiac arrhythmias. In support of this possibility, we show that PUFA analogs act...

  3. Decision-tree model for health economic comparison of two long-acting somatostatin receptor ligand devices in France, Germany, and the UK.

    Science.gov (United States)

    Marty, Rémi; Roze, Stéphane; Kurth, Hannah

    2012-01-01

    Long-acting somatostatin receptor ligands (SRL) with product-specific formulation and means of administration are injected periodically in patients with acromegaly and neuroendocrine tumors. A simple decision-tree model aimed at comparing cost savings with ready-to-use Somatuline Autogel(®) (lanreotide) and Sandostatin LAR(®) (octreotide) for the UK, France, and Germany. The drivers of cost savings studied were the reduction of time to administer as well as a reduced baseline risk of clogging during product administration reported for Somatuline Autogel(®). The decision-tree model assumed two settings for SRL administration, ie, by either hospital-based or community-based nurses. In the case of clogging, the first dose was assumed to be lost and a second injection performed. Successful injection depended on the probability of clogging. Direct medical costs were included. A set of scenarios were run, varying the cost drivers, such as the baseline risk of clogging, SRL administration time, and percentage of patients injected during a hospital stay. Costs per successful injection were less for Somatuline Autogel(®)/Depot, ranging from Euros (EUR) 13-45, EUR 52-108, and EUR 127-151, respectively, for France, Germany, and the UK. The prices for both long-acting SRL were the same in France, and cost savings came to 100% from differences other than drug prices. For Germany and the UK, the proportion of savings due to less clogging and shorter administration time was estimated to be around 32% and 20%, respectively. Based on low and high country-specific patient cohort size estimations of individuals eligible for SRL treatment among the patient population with acromegaly and neuroendocrine tumors, annual savings were estimated to be up to EUR 2,000,000 for France, EUR 6,000,000 for Germany, and EUR 7,000,000 for the UK. This model suggests that increasing usage of the Somatuline device for injection of SRL might lead to substantial savings for health care providers

  4. Low frequency of cardniac arrhythmias and lack of structural heart disease in medically-naïve acromegaly patients: a prospective study at baseline and after 1 year of somatostatin analogs treatment.

    Science.gov (United States)

    Warszawski, Leila; Kasuki, Leandro; Sá, Rodrigo; Dos Santos Silva, Cintia Marques; Volschan, Isabela; Gottlieb, Ilan; Pedrosa, Roberto Coury; Gadelha, Mônica R

    2016-12-01

    The incidence of arrhythmias may be increased in acromegaly, but the pathophysiologic mechanisms involved are still unclear, and it has never been correlated with structural heart changes analyzed by the gold-standard method cardiac magnetic resonance (CMR). Evaluate the frequency of arrhythmias in drug-naïve acromegaly patients at baseline and after 1 year of somatostatin analogs (SA) treatment and to correlate the occurrence of arrhythmias with the presence of structural heart changes. Consecutive drug-naïve acromegaly patients were recruited. The occurrence of arrhythmias and structural heart changes were studied through 24-h Holter and CMR, respectively, at baseline and after 1-year SA treatment. Thirty-six patients were studied at baseline and 28 were re-evaluated after 1 year of SA treatment. There were 13 females and median age was 48 years (20-73 years). Nine patients (32 %) were controlled after treatment. No sustained arrhythmias were reported in the 24-h Holter. No arrhythmia-related symptoms were observed. Only two patients presented left ventricular hypertrophy and three patients presented fibrosis at baseline. There was no correlation of the left ventricular mass with the number of episodes of arrhythmias and they were not more prevalent in the patients presenting cardiac fibrosis. We found no sustained arrhythmias and a lack of arrhythmia-related symptoms at baseline and after 1 year of SA treatment in a contemporary cohort of acromegaly patients that also present a low frequency of structural heart changes, indicating that these patients may have a lower frequency of heart disease than previously reported.

  5. Clinical outcome and evidence of high rate post-surgical anterior hypopituitarism in a cohort of TSH-secreting adenoma patients: Might somatostatin analogs have a role as first-line therapy?

    Science.gov (United States)

    Gatto, Federico; Grasso, Ludovica F; Nazzari, Elena; Cuny, Thomas; Anania, Pasquale; Di Somma, Carolina; Colao, Annamaria; Zona, Gianluigi; Weryha, Georges; Pivonello, Rosario; Ferone, Diego

    2015-10-01

    Thyrotropin-secreting pituitary adenomas (TSHomas) represent a rare subtype of pituitary tumors. Neurosurgery (NCH) is still considered the first-line therapy. In this study we aimed to investigate the outcome of different treatment modalities, including first line somatostatin analogs (SSA) treatment, with a specific focus on neurosurgery-related complications. We retrospectively evaluated thirteen patients diagnosed for TSHomas (9 M; age range 27-61). Ten patients had a magnetic resonance evidence of macroadenoma, three with slight visual field impairment. In the majority of patients, thyroid ultrasonography showed the presence of goiter and/or increased gland vascularization. Median TSH value at diagnosis was 3.29 mU/L (normal ranges 0.2-4.2 mIU/L), with median fT4 2.52 ng/dL (0.9-1.7 ng/dL). Three patients (two microadenoma) were primarily treated with NCH and achieved disease remission, whereas ten patients (nine macroadenomas) were initially treated with SSA. Despite the optimal biochemical response observed during medical treatment in most patients (mean TSH decrease -72%), only two stayed on medical therapy alone, achieving stable biochemical control at the end of the follow-up. The remaining patients (n = 7) underwent NCH later on during their clinical history, followed by radiotherapy or adjuvant SSA treatment in two cases. Noteworthy, five of them developed hypopituitarism. All patients reached a biochemical control, after a multimodal therapeutic approach. Neurosurgery ultimately led to complete disease remission or to biochemical control in majority of patients, whereas resulting in a considerable percentage of post-operative complications (mainly hypopituitarism, 50%). In the light of the optimal results unanimously reported for medical treatment with SSA, our experience suggests that a careful evaluation of risk/benefit ratio should be taken into consideration when directing the treatment approach in patients with TSHoma.

  6. Electrochemical separation of 90-yttrium in the electrochemical 90Sr/90Y generator and its use for radiolabelling of DOTA-conjugated somatostatin analog [DOTA0, Tyr3] octreotate

    Directory of Open Access Journals (Sweden)

    Petrović Đorđe Ž.

    2012-01-01

    Full Text Available Radiopharmaceuticals based on 90Y are widely used in the treatment of malignant deseases. In order to meet the requirements for their future application, a 90Sr/90Y generator was developed and 90Y eluted from this locally produced generator was used for the radiolabelling of the DOTA-conjugated somatostatin analog [DOTA0,Tyr3] octreotate and the preparation of [90Y-DOTA0,Tyr3] octreotate (90Y-DOTATATE for peptide receptore radionuclide therapy. 90Sr/90Y generator was based on the electrochemical separation of 90Y from 90Sr in a two-cycle electrolysis procedure. Three electrode cells were used to perform both electrolyses. In both cycles, working electrodes were kept on constant potential. The pH of the solution was adjusted to 2.7 of the value before the electrolyses. The radionuclidic purity of the 90Y solution was analysed by ITLC and extraction paper chromatography. The labelling of peptide (100 mg DOTATATE with 90YCl3 was performed at 95°C for 30 minutes. Radiochemical purity was determined by HPLC and chromatographic separation, using a solid SepPak C-18 column. Results obtained confirmed the efficiency of our electrochemical separation technique and quality control methods for 90Y. The achieved efficiency of the 90Sr/90Y generator above 96% of the theoretical value represents a good basis for the further development of this generator. The labelling of the DOTATATE with 90Y exhibited a high efficiency, too: there was less than 1% of 90Y3+in the 90Y-DOTATATE.

  7. Somatostatin: a metabolic regulator

    International Nuclear Information System (INIS)

    Dileepan, K.N.; Wagle, S.R.

    1985-01-01

    Somatostatin, the hypothalamic release-inhibiting factor, has been found to stimulate gluconeogenesis in rat kidney cortical slices. Stimulation by somatostatin was linear and dose-dependent. Other bioactive peptides such as cholecystokinin, gastro-intestinal peptide, secretin, neurotensin, vasoactive intestinal peptide, pancreatic polypeptide, beta endorphin and substance P did not affect the renal gluconeogenic activity. Somatostatin-induced gluconeogenesis was blocked by phentolamine (alpha adrenergic antagonist) and prazosin (alpha 1 adrenergic antagonist) but not by propranolol (beta adrenergic antagonist) and yohimbine (alpha 2 adrenergic antagonist) suggesting that the effect is via alpha 1 adrenergic stimuli. Studies on the involvement of Ca 2+ revealed that tissue depletion and omission of Ca 2+ from the reaction mixture would abolish the stimulatory effect of somatostatin. Furthermore, somatostatin enhanced the uptake of 45 calcium in renal cortical slices which could be blocked by lanthanum, an inhibitor of Ca 2+ influx. It is proposed that the stimulatory effect of somatostatin on renal gluconeogenesis is mediated by alpha 1 adrenergic receptors, or those which functionally resemble the alpha 1 receptors and that the increased influx of Ca 2+ may be the causative factor for carrying out the stimulus. 88 references

  8. Somatostatin: a metabolic regulator

    Energy Technology Data Exchange (ETDEWEB)

    Dileepan, K.N.; Wagle, S.R.

    1985-12-23

    Somatostatin, the hypothalamic release-inhibiting factor, has been found to stimulate gluconeogenesis in rat kidney cortical slices. Stimulation by somatostatin was linear and dose-dependent. Other bioactive peptides such as cholecystokinin, gastro-intestinal peptide, secretin, neurotensin, vasoactive intestinal peptide, pancreatic polypeptide, beta endorphin and substance P did not affect the renal gluconeogenic activity. Somatostatin-induced gluconeogenesis was blocked by phentolamine (alpha adrenergic antagonist) and prazosin (alpha/sub 1/ adrenergic antagonist) but not by propranolol (beta adrenergic antagonist) and yohimbine (alpha/sub 2/ adrenergic antagonist) suggesting that the effect is via alpha/sub 1/ adrenergic stimuli. Studies on the involvement of Ca/sup 2 +/ revealed that tissue depletion and omission of Ca/sup 2 +/ from the reaction mixture would abolish the stimulatory effect of somatostatin. Furthermore, somatostatin enhanced the uptake of /sup 45/calcium in renal cortical slices which could be blocked by lanthanum, an inhibitor of Ca/sup 2 +/ influx. It is proposed that the stimulatory effect of somatostatin on renal gluconeogenesis is mediated by alpha/sub 1/ adrenergic receptors, or those which functionally resemble the alpha/sub 1/ receptors and that the increased influx of Ca/sup 2 +/ may be the causative factor for carrying out the stimulus. 88 references.

  9. Validation of somatostatin receptor scintigraphy in the localization of neuroendocrine tumors

    International Nuclear Information System (INIS)

    Lamberts, S.W.J.; Reubi, J.C.; Krenning, E.P.

    1993-01-01

    Somatostatin analogs are used in the control of hormonal hypersecretion and tumor growth of patients with acromegaly, islet cell carcinomas and carcinoids. Recently we showed that somatostatin receptor positive tumors can be visualized in vivo after the administration of radionuclide-labeled somatostatin analogs. Receptor imaging was positive in 18/21 islet cell tumors, 32/37 carcinoids, 26/28 paragangliomas, 9/14 medullary thyroid carcinomas, and 5/7 small cell lung cancers. Somatostatin receptor imaging is an easy, harmless and painless diagnostic method. It localizes multiple and/or metastatic tumors, predicts the successful control of hormonal hypersecretion by octreotide and seems to be of prognostic value in certain types of cancer. This scintigraphic method might help in patient selection for clinical trials with somatostatin analogs in the treatment of neuroendocrine cancers. (orig.)

  10. Validation of somatostatin receptor scintigraphy in the localization of neuroendocrine tumors

    Energy Technology Data Exchange (ETDEWEB)

    Lamberts, S.W.J. (Depts. of Medicine and Nuclear Medicine, Erasmus Univ., Rotterdam (Netherlands) Div. of Cell Biology and Experimental Cancer Research, Institution of Pathology, Bern Univ. (Switzerland)); Reubi, J.C. (Depts. of Medicine and Nuclear Medicine, Erasmus Univ., Rotterdam (Netherlands) Div. of Cell Biology and Experimental Cancer Research, Institution of Pathology, Bern Univ. (Switzerland)); Krenning, E.P. (Depts. of Medicine and Nuclear Medicine, Erasmus Univ., Rotterdam (Netherlands) Div. of Cell Biology and Experimental Cancer Research, Institution of Pathology, Bern Univ. (Switzerland))

    1993-01-01

    Somatostatin analogs are used in the control of hormonal hypersecretion and tumor growth of patients with acromegaly, islet cell carcinomas and carcinoids. Recently we showed that somatostatin receptor positive tumors can be visualized in vivo after the administration of radionuclide-labeled somatostatin analogs. Receptor imaging was positive in 18/21 islet cell tumors, 32/37 carcinoids, 26/28 paragangliomas, 9/14 medullary thyroid carcinomas, and 5/7 small cell lung cancers. Somatostatin receptor imaging is an easy, harmless and painless diagnostic method. It localizes multiple and/or metastatic tumors, predicts the successful control of hormonal hypersecretion by octreotide and seems to be of prognostic value in certain types of cancer. This scintigraphic method might help in patient selection for clinical trials with somatostatin analogs in the treatment of neuroendocrine cancers. (orig.).

  11. Evolutionary history of the somatostatin and somatostatin receptors

    Indian Academy of Sciences (India)

    Somatostatin and its receptors have a critical role in mammalian growth through their control pattern of secretion of growth hormone, but the evolutionary history of somatostatin and somatostatin receptors are ill defined. We used comparative whole genome analysis of Danio rerio, Carassius auratus, Xenopus tropicalis, ...

  12. Effect of subcutaneous injection of a long-acting analogue of somatostatin (SMS 201-995) on plasma thyroid-stimulating hormone in normal human subjects

    Energy Technology Data Exchange (ETDEWEB)

    Itoh, S.; Tanaka, K.; Kumagae, M.; Takeda, F.; Morio, K.; Kogure, M.; Hasegawa, M.; Horiuchi, T.; Watabe, T.; Miyabe, S.

    1988-01-01

    SMS 201-995 (SMS), a synthetic analogue of somatostatin (SRIF) has been shown to be effective in the treatment of the hypersecretion of hormones such as in acromegaly. However, little is known about the effects of SMS on the secretion of thyroid-stimulating hormone (TSH) in normal subjects. In this study, plasma TSH was determined with a highly sensitive immunoradiometric assay, in addition to the concentration of SMS in plasma and urine with a radioimmunoassay, following subcutaneous injection of 25, 50, 100 ..mu..g of SMS or a placebo to normal male subjects, at 0900 h after an overnight fast. The plasma concentrations of SMS were dose-responsive and the peak levels were 1.61 +/- 0.09, 4.91 +/- 0.30 and 8.52 +/- 1.18 ng/ml, which were observed at 30, 15 and 45 min after the injection of 25, 50, and 100 ..mu..g of SMS, respectively. Mean plasma disappearance half-time of SMS was estimated to be 110 +/- 3 min. Plasma TSH was suppressed in a dose dependent manner and the suppression lasted for at least 8 hours. At 8 hours after the injection of 25, 50, and 100 ..mu..g of SMS, the plasma TSH levels were 43.8 +/- 19.4, 33.9 +/- 9.4 and 24.9 +/- 3.2%, respectively, of the basal values.

  13. Efficacy and Safety of Rapid-Acting Insulin Analogs in Special Populations with Type 1 Diabetes or Gestational Diabetes

    DEFF Research Database (Denmark)

    Nørgaard, Kirsten; Sukumar, Nithya; Rafnsson, Snorri B

    2018-01-01

    Med, EMBASE and Cochrane Reviews were searched electronically, and their bibliographies examined to identify suitable studies for review and inclusion in a meta-analysis. Eligible studies were randomized controlled trials that reported data on relevant clinical outcomes. A different reviewer abstracted data...... concerns. Meta-analysis indicated severe hypoglycemic events were comparable for rapid-acting insulin analogs versus RHI (risk difference: 0.00 [95% confidence interval - 0.01; 0.01]). In the pregnancy group, insulin lispro and insulin aspart were safe and effective for both mother and fetus, with glycemic......INTRODUCTION: To assess the efficacy and safety of three available rapid-acting insulin analogs (insulins lispro, aspart and glulisine, respectively) in pregnant women, children/adolescents and people using continuous subcutaneous insulin infusion (CSII) with type 1 diabetes. METHODS: Pub...

  14. Radiopharmaceutical development of a freeze-dried kit formulation for the preparation of [99mTc-EDDA-HYNIC-D-Phe1, Tyr3]-octreotide, a somatostatin analog for tumor diagnosis.

    Science.gov (United States)

    Guggenberg, Elisabeth Von; Mikolajczak, Renata; Janota, Barbara; Riccabona, Georg; Decristoforo, Clemens

    2004-10-01

    [(99m)Tc-EDDA-HYNIC-D-Phe(1),Tyr(3)]-Octreotide ((99m)Tc-EDDA/HYNIC-TOC) is a promising new radiopharmaceutical with the potential to replace [(111)In-DTPA-D-Phe(1)]-Octreotide ((111)In-DTPA-OCT) as the radiopharmaceutical for somatostatin receptor scintigraphy due to the advantage of improved image quality, lower radiation dose for the patient, and daily availability. Here we describe the development of a freeze-dried kit formulation based on the Tricine/EDDA exchange labeling approach for the preparation of this radiopharmaceutical in a clinical setting. Three parameters were of major importance to achieve a suitable formulation with a radiochemical purity (RCP) >90%: addition of bulking agent, the pH of the freeze-drying solution, and the content of stannous chloride. The final formulation consisted of 20 mg Tricine, 10 mg EDDA, 50 mg Mannitol, 20 microg SnCl(2). 2H(2)O, and 20 microg [HYNIC-D-Phe(1), Tyr(3)]-Octreotide (HYNIC-TOC). Radiolabeling was performed by addition of 0.2 M Na(2)HPO(4) to adjust the pH to 6-7, followed by 0.5-2 GBq (99m)Tc sodium pertechnetate, in a total volume of 2 mL and incubation for 10 min in a boiling water bath. Mean RCP values of 10 batches showed values >90% over a storage period of up to 1 year, a high stability up to 24 h of the final preparation, and retained biological activity. The developed kit formulation forms the basis for further clinical evaluation of this promising new radiopharmaceutical. Copyright 2004 Wiley-Liss, Inc. and the American Pharmacists Association

  15. Evolutionary history of the somatostatin and somatostatin receptors

    Indian Academy of Sciences (India)

    Table 1. The identified somatostations. Somatostatin (SST1). Name. Scientific name. Length. High ID (to). Low ID (to) Chromosome. GS. Drs. Danio rerio. 324. 48.1 mms ...... ancestral source. References. Baranowska B., Chmielowska M., Wolinska-Witort E., Bik W.,. Baranowska-Bik A. and Martynska L. 2006 Direct effect of.

  16. Sensitive radioimmunoassay for somatostatin using N-(/sup 125/I)-tyr-somatostatin as labelled antigen

    Energy Technology Data Exchange (ETDEWEB)

    Dupont, A [CHUL, Quebec (Canada). Lab. of Molecular Endocrinology and Service of Gastro-Enterology; Coy, D H; Alvarado-Urbina, G; Cote, J; Meyers, C A; McManus, J; Barden, N; De Lean, A; Labrie, F

    1979-01-01

    A sensitive radioimmunoassay for somatostatin using N-(/sup 125/I)-Tyr-somatostatin is described and compared with using (/sup 125/I)-Tyr/sup 1/-somatostatin. The minimum detectable amount of somatostatin using N-(/sup 125/I)-Tyr-somatostatin as tracer was 0.1 to 0.5 pg, which is approximately 10-fold lower detection limit of the RIA using (/sup 125/I)-Tyr/sup 1/-somatostatin. Moreover, it was found that the shelf-life of N-(/sup 125/I)-Tyr-somatostatin was prolonged in comparison with labelled Tyr/sup 1/-somatostatin. Human pancreatic and gastric extracts displayed immunological similarity to synthetic somatostatin tetradecapeptide.

  17. The long-acting somatostatin analogue octreotide alleviates symptoms by reducing posttranslational conversion of prepro-glucagon to glucagon in a patient with malignant glucagonoma, but does not prevent tumor growth

    NARCIS (Netherlands)

    F. Jockenhövel (F.); S. Lederbogen (S.); T. Olbricht (T.); H. Schmidt-Gayk (H.); E.P. Krenning (Eric); S.W.J. Lamberts (Steven); D. Reinwein (D.)

    1994-01-01

    textabstractA 52-year-old female with metastatic glucagonoma secreting glucagon and chromogranin A was treated with the somatostatin analogue octreotide for 2 years without any additional tumor-reducing interventions. Before therapy plasma glucagon was above 8 μg/l (normal <0.2) and within 2 days 3

  18. Carboxyl-terminal multi-site phosphorylation regulates internalization and desensitization of the human sst2 somatostatin receptor.

    Science.gov (United States)

    Lehmann, Andreas; Kliewer, Andrea; Schütz, Dagmar; Nagel, Falko; Stumm, Ralf; Schulz, Stefan

    2014-04-25

    The somatostatin receptor 2 (sst2) is the pharmacological target of somatostatin analogs that are widely used in the diagnosis and treatment of human neuroendocrine tumors. We have recently shown that the stable somatostatin analogs octreotide and pasireotide (SOM230) stimulate distinct patterns of sst2 receptor phosphorylation and internalization. Like somatostatin, octreotide promotes the phosphorylation of at least six carboxyl-terminal serine and threonine residues namely S341, S343, T353, T354, T356 and T359, which in turn leads to a robust receptor endocytosis. Unlike somatostatin, pasireotide stimulates a selective phosphorylation of S341 and S343 of the human sst2 receptor followed by a partial receptor internalization. Here, we show that exchange of S341 and S343 by alanine is sufficient to block pasireotide-driven internalization, whereas mutation of T353, T354, T356 and T359 to alanine is required to strongly inhibited both octreotide- and somatostatin-induced internalization. Yet, combined mutation of T353, T354, T356 and T359 is not sufficient to prevent somatostatin-driven β-arrestin mobilization and receptor desensitization. Replacement of all fourteen carboxyl-terminal serine and threonine residues by alanine completely abrogates sst2 receptor internalization and β-arrestin mobilization in HEK293 cells. Together, our findings demonstrate for the first time that agonist-selective sst2 receptor internalization is regulated by multi-site phosphorylation of its carboxyl-terminal tail. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. Development and preclinical evaluation of radiolabelled somatostatin receptor agonists and αvβ3-integrin antagonists

    International Nuclear Information System (INIS)

    Stoecklin, G.; Wester, H.J.; Haubner, R.; Schottelius, M.

    2002-01-01

    Tumours express specific receptors for peptide ligands. This can be exploited for tumour targeting. New bioactive peptides are available, in particular new somatostatin analogs and RGD-Peptides for targeting the α V β 3 -integrin. The design and optimization of radiolabelled peptides with respect to their receptor affinity, tumour uptake, biodistribution, pharmacokinetics and stability may provide better tracers for tumour imaging and therapy. Based on two basic structures, new radioiodinated and carbohydrated somatostatin analogs and cyclic RGD-peptides were developed and evaluated. (author)

  20. Scintigraphy with labelled analogues of the somatostatin

    International Nuclear Information System (INIS)

    Duet, M.; Ajzenberg, C.; Warnet, A.; Mundler, O.

    1998-01-01

    The receptors of the somatostatin have been localized in a big number of tumors, whom a great number are neuro-endocrine tumors. However, some tumors that have not this differentiation (breast cancer, lymphomas, cerebral tumors) possess them as well. Analogues of somatostatin, labelled with isotopes having a gamma emission, allow from now their detection in vivo. (N.C.)

  1. Rationale-Based Engineering of a Potent Long-Acting FGF21 Analog for the Treatment of Type 2 Diabetes.

    Directory of Open Access Journals (Sweden)

    Randy Hecht

    Full Text Available Fibroblast growth factor 21 (FGF21 is a promising drug candidate for the treatment of type 2 diabetes. However, the use of wild type native FGF21 is challenging due to several limitations. Among these are its short half-life, its susceptibility to in vivo proteolytic degradation and its propensity to in vitro aggregation. We here describe a rationale-based protein engineering approach to generate a potent long-acting FGF21 analog with improved resistance to proteolysis and aggregation. A recombinant Fc-FGF21 fusion protein was constructed by fusing the Fc domain of human IgG1 to the N-terminus of human mature FGF21 via a linker peptide. The Fc positioned at the N-terminus was determined to be superior to the C-terminus as the N-terminal Fc fusion retained the βKlotho binding affinity and the in vitro and in vivo potency similar to native FGF21. Two specific point mutations were introduced into FGF21. The leucine to arginine substitution at position 98 (L98R suppressed FGF21 aggregation at high concentrations and elevated temperatures. The proline to glycine replacement at position 171 (P171G eliminated a site-specific proteolytic cleavage of FGF21 identified in mice and cynomolgus monkeys. The derived Fc-FGF21(RG molecule demonstrated a significantly improved circulating half-life while maintaining the in vitro activity similar to that of wild type protein. The half-life of Fc-FGF21(RG was 11 h in mice and 30 h in monkeys as compared to 1-2 h for native FGF21 or Fc-FGF21 wild type. A single administration of Fc-FGF21(RG in diabetic mice resulted in a sustained reduction in blood glucose levels and body weight gains up to 5-7 days, whereas the efficacy of FGF21 or Fc-FGF21 lasted only for 1 day. In summary, we engineered a potent and efficacious long-acting FGF21 analog with a favorable pharmaceutical property for potential clinical development.

  2. Dulaglutide, a long-acting GLP-1 analog fused with an Fc antibody fragment for the potential treatment of type 2 diabetes

    DEFF Research Database (Denmark)

    Jimenez-Solem, Espen; Rasmussen, Mette H; Christensen, Mikkel

    2010-01-01

    Dulaglutide (LY-2189265) is a novel, long-acting glucagon-like peptide 1 (GLP-1) analog being developed by Eli Lilly for the treatment of type 2 diabetes mellitus (T2DM). Dulaglutide consists of GLP-1(7-37) covalently linked to an Fc fragment of human IgG4, thereby protecting the GLP-1 moiety from...

  3. Treatment of Type 1 and Type 2 Diabetes Mellitus with Insulin Detemir, a Long-Acting Insulin Analog

    Directory of Open Access Journals (Sweden)

    Jason R. Young

    2010-01-01

    Full Text Available Insulin detemir is a long-acting basal insulin approved for use in patients with type 1 (T1DM or type 2 diabetes (T2DM. Insulin detemir has demonstrated equivalent glycemic control and hypoglycemic risk when compared to insulin glargine, and insulin detemir has generally but not consistently demonstrated less weight gain than insulin glargine in T2DM. The benefits of basal insulin analogs relative to NPH insulin are well recognized, including less FBG variability, lower risk of hypoglycemia, and less weight gain specifically with insulin detemir. However, NPH insulin continues to be widely prescribed, which may be due in part to economic considerations. While NPH insulin generally costs less per prescription, insulin detemir has been shown to be cost effective compared to NPH insulin as well as insulin glargine. Therefore, insulin detemir is an effective option from both clinical and economic perspectives for patients with T1DM or T2DM who require basal insulin to achieve glycemic control.

  4. Serial follow-up of presurgical treatment using pasireotide long-acting release with or without octreotide long-acting release for naïve active acromegaly

    Directory of Open Access Journals (Sweden)

    Jan-Shun Chang

    2016-06-01

    Full Text Available The aim of the present study was to evaluate the serial changes of GH and IGF-1 in seven patients with naïve, active acromegaly following presurgical treatment of the somatostatin analog pasireotide long-acting release (LAR and octreotide LAR. The patients were treated with pasireotide LAR with or without octreotide LAR for two years and underwent transsphenoidal adenomectomy. After treatment with the somatostatin analogs, the surgical cure rate was similar to that in patients who underwent transsphenoidal surgery alone. Diabetes insipidus was not identified in any patients after the operation. Pasireotide LAR was effective on GH as well as IGF-1 suppression and tumor size decreasing when used as the primary therapy. Future large-population studies to investigate the surgical curative rate after presurgical treatment with somatostatin analogs in patients with acromegaly and macroadenomas close to the cavernous sinus are warranted. However, that hyperglycemia developed following pre-surgical treatment with pasireotide should take into consideration.

  5. Somatostatin in the caudal spinal cord

    DEFF Research Database (Denmark)

    Schrøder, H D

    1984-01-01

    . In all of these regions somatostatin-positive cell bodies were also observed. In the intermediate gray matter stained terminals were present around the central canal in a varying number. The most prominent stainability was found in the lumbosacral transition zone. Many terminals were also observed...... was particularly low in the motoneuron neuropil. However, a dense somatostatin network was found in the sixth lumbar segment in relation to the neurons in Onuf's nucleus X complex, the nucleus that innervates the small pelvic muscles including the striated sphincters. It is concluded that somatostatin, besides...

  6. Treating Type 1 Diabetes Mellitus with a Rapid-Acting Analog Insulin Regimen vs. Regular Human Insulin in Germany: A Long-Term Cost-Effectiveness Evaluation.

    Science.gov (United States)

    Valentine, William J; Van Brunt, Kate; Boye, Kristina S; Pollock, Richard F

    2018-06-01

    The aim of the present study was to evaluate the cost effectiveness of rapid-acting analog insulin relative to regular human insulin in adults with type 1 diabetes mellitus in Germany. The PRIME Diabetes Model, a patient-level, discrete event simulation model, was used to project long-term clinical and cost outcomes for patients with type 1 diabetes from the perspective of a German healthcare payer. Simulated patients had a mean age of 21.5 years, duration of diabetes of 8.6 years, and baseline glycosylated hemoglobin of 7.39%. Regular human insulin and rapid-acting analog insulin regimens reduced glycosylated hemoglobin by 0.312 and 0.402%, respectively. Compared with human insulin, hypoglycemia rate ratios with rapid-acting analog insulin were 0.51 (non-severe nocturnal) and 0.80 (severe). No differences in non-severe diurnal hypoglycemia were modeled. Discount rates of 3% were applied to future costs and clinical benefits accrued over the 50-year time horizon. In the base-case analysis, rapid-acting analog insulin was associated with an improvement in quality-adjusted life expectancy of 1.01 quality-adjusted life-years per patient (12.54 vs. 11.53 quality-adjusted life-years). Rapid-acting analog insulin was also associated with an increase in direct costs of €4490, resulting in an incremental cost-effectiveness ratio of €4427 per quality-adjusted life-year gained vs. human insulin. Sensitivity analyses showed that the base case was driven predominantly by differences in hypoglycemia; abolishing these differences reduced incremental quality-adjusted life expectancy to 0.07 quality-adjusted life-years, yielding an incremental cost-effectiveness ratio of €74,622 per quality-adjusted life-year gained. Rapid-acting analog insulin is associated with beneficial outcomes in patients with type 1 diabetes and is likely to be considered cost effective in the German setting vs. regular human insulin.

  7. Somatostatin receptor scintigraphy in endocrine ophthalmopathy; Somatostatin-Rezeptor-Szintigraphie bei endokriner Orbitopathie

    Energy Technology Data Exchange (ETDEWEB)

    Diaz, M. [Klinik und Poliklinik fuer Nuklearmedizin, Univ. Mainz (Germany); Kahaly, G. [3. Medizinische Klinik und Poliklinik, Innere Medizin - Endokrinologie, Univ. Mainz (Germany); Muehlbach, A. [3. Medizinische Klinik und Poliklinik, Innere Medizin - Endokrinologie, Univ. Mainz (Germany); Bockisch, A. [Klinik und Poliklinik fuer Nuklearmedizin, Univ. Mainz (Germany); Beyer, J. [3. Medizinische Klinik und Poliklinik, Innere Medizin - Endokrinologie, Univ. Mainz (Germany); Hahn, K. [Klinik und Poliklinik fuer Nuklearmedizin, Univ. Mainz (Germany)

    1994-12-01

    Somatostatin receptor scintigraphy with {sup 111}In-labeled octreotide proves to be a very sensitive diagnostic tool for evaluation of inflammative activity in endocrine ophthalmopathy (EO). The results of somatostatin receptor scintigraphy (SRS) in 40 patients with EO show a high orbital accumulation of {sup 111}In-octreotide in clinically active EO (4h-median/orbit-brain-ratio: 12.6; controls 4h-median: 5.8) Patients with clinically inactive EO (4h-median: 7.1) show a similar orbital accumulation of radioactivity compared to controls. 5 patients with active orbital myositis also revealed an even higher orbital accumulation of radioactivity (4h-median: 42.3). The diagnostic value of SRS lies in its ability to act as a measure of inflammation and an be useful as an activity parameter when planning therapeutic procedure as well as for EO follow-up. The results in patients with orbital myositis nevertheless do not permit a differential diagnosis with this method. The therapeutic value of {sup 111}In-octreotide in Graves` disease has yet to be established. (orig.) [Deutsch] Die Somatostatin-Rezeptor-Szintigraphie (SRS) mit dem {sup 111}Indium-markierten Somatostatinanalogon Octreotid stellt ein sensitives Verfahren zur Einschaetzung der entzuendlichen Aktivitaet bei endokriner Orbitopathie (EO) dar. Die Untersuchungen an 40 Patienten mit EO ergaben eine im Vergleich zur Kontrollgruppe signifikant hoehere orbitale Octreotidanreicherung bei klinisch aktiver Erkrankung (4h-Median/Orbita-Hirn-Quotient: 12,6; Kontrollgruppe 4h-Median: 5,8; p=0,0032). Patienten mit klinisch nicht aktiver Erkrankung (4h-Median: 7,1) unterschieden sich bezueglich der orbitalen Octreotidanreicherung nicht wesentlich von der Kontrollgruppe. Auch 5 Patienten mit florider orbitaler Myositis zeigten eine deutlich gesteigerte orbitale Aktivitaetsanreicherung (4h-Median: 42,3). Der diagnostische Nutzen der SRS liegt somit in ihrer Eigenschaft als Aktivitaets- und Entzuendungsparameter und kann mit

  8. Transcriptional and Functional Characterization of the G Protein-Coupled Receptor Repertoire of Gastric Somatostatin Cells

    DEFF Research Database (Denmark)

    Egerod, Kristoffer L; Engelstoft, Maja S; Lund, Mari L

    2015-01-01

    In the stomach, somatostatin (SST) acts as a general paracrine negative regulator of exocrine secretion of gastric acid and pepsinogen and endocrine secretion of gastrin, ghrelin, and histamine. Using reporter mice expressing red fluorescent protein (RFP) under control of the SST promotor, we hav...

  9. Activation of somatostatin 2 receptors in the brain and the periphery induces opposite changes in circulating ghrelin levels: functional implications

    Directory of Open Access Journals (Sweden)

    Andreas eStengel

    2013-01-01

    Full Text Available Somatostatin is an important modulator of neurotransmission in the central nervous system and acts as a potent inhibitor of hormone and exocrine secretion and regulator of cell proliferation in the periphery. These pleiotropic actions occur through interaction with five G-protein coupled somatostatin receptor subtypes (sst1-5 that are widely expressed in the brain and peripheral organs. The characterization of somatostatin’s effects can be investigated by pharmacological or genetic approaches using newly developed selective sst agonists and antagonists and mice lacking specific sst subtypes. Recent evidence points towards a divergent action of somatostatin in the brain and in the periphery to regulate circulating levels of ghrelin, an orexigenic hormone produced by the endocrine X/A-like cells in the gastric mucosa. Somatostatin interacts with the sst2 in the brain to induce an increase in basal ghrelin plasma levels and counteracts the visceral stress-related decrease in circulating ghrelin in rats. By contrast, stimulation of peripheral somatostatin-sst2 signaling results in the inhibition of basal ghrelin release and mediates the postoperative decrease in circulating ghrelin in rats. The peripheral sst2-mediated reduction of plasma ghrelin is likely to involve a paracrine action of D-cell derived somatostatin acting on sst2 bearing X/A-like ghrelin cells in the gastric mucosa. The other member of the somatostatin family, named cortistatin, in addition to binding to sst1-5 also directly interacts with the ghrelin receptor and therefore may simultaneously modulate ghrelin release and actions at target sites bearing ghrelin receptors representing a link between the ghrelin and somatostatin systems.

  10. Correlation of Somatostatin Receptor-2 Expression with Gallium-68-DOTA-TATE Uptake in Neuroblastoma Xenograft Models

    OpenAIRE

    Zhang, Libo; Vines, Douglass C.; Scollard, Deborah A.; McKee, Trevor; Komal, Teesha; Ganguly, Milan; Do, Trevor; Wu, Bing; Alexander, Natasha; Vali, Reza; Shammas, Amer; Besanger, Travis; Baruchel, Sylvain

    2017-01-01

    Peptide-receptor imaging and therapy with radiolabeled somatostatin analogs such as 68Ga-DOTA-TATE and 177Lu-DOTA-TATE have become an effective treatment option for SSTR-positive neuroendocrine tumors. The purpose of this study was to evaluate the correlation of somatostatin receptor-2 (SSTR2) expression with 68Ga-DOTA-TATE uptake and 177Lu-DOTA-TATE therapy in neuroblastoma (NB) xenograft models. We demonstrated variable SSTR2 expression profiles in eight NB cell lines. From micro-PET imagin...

  11. Kidney protection during peptide receptor radionuclide therapy with somatostatin analogues.

    NARCIS (Netherlands)

    Rolleman, E.J.; Melis, M.; Valkema, R.; Boerman, O.C.; Krenning, E.P.; Jong, M. de

    2010-01-01

    This review focuses on the present status of kidney protection during peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues. This treatment modality for somatostatin receptor-positive tumours is limited by renal reabsorption and retention of radiolabelled peptides

  12. Somatostatin receptors in gastroentero-pancreatic neuroendocrine tumours

    NARCIS (Netherlands)

    W.W. de Herder (Wouter); L.J. Hofland (Leo); A-J. van der Lely (Aart-Jan); S.W.J. Lamberts (Steven)

    2003-01-01

    textabstractFive somatostatin receptor (sst) subtype genes, sst(1), sst(2), sst(3), sst(4) and sst(5), have been cloned and characterised. The five sst subtypes all bind natural somatostatin-14 and somatostatin-28 with high affinity. Endocrine pancreatic and endocrine digestive

  13. Radioimmunoassay of somatostatin: methodological problems and physiological investigations

    International Nuclear Information System (INIS)

    Penman, E.; Wass, J.A.H.

    1981-01-01

    Somatostatin, a tetradecapeptide, has a wide distribution throughout the central nervous system and the gastrointestinal tract and a broad spectrum of biological actions. In order to investigate its various physiological roles in man, a radioimmunoassay was developed for somatostatin in human blood plasma, which is described here. This RIA was used to investigate possible factors influencing somatostatin secretion. Changes in somatin levels produced by changes in insulin, glucagon and growth hormone levels were studied via the response of plasma immunoreactive somatostatin to hormonal stimuli in normal man. The influence of fasting and food consumption was studied; and the site of origin of circulating immunoreactive somatostatin was investigated in patients. (Auth.)

  14. Ga-68 Somatostatin Receptor PET/CT in von Hippel-Lindau Disease

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Jong-Ryool; Min, Jung-Joon [Chonnam National Univ. Hwasun Hospital, Hwasun (Korea, Republic of); Kulkarui, Harshad; Carreras, Cecilia; Schalch, Georg; Baum, Richard P. [Nuclear Medicine and Center for PET/CT, Zentralk Bad Berka, Bad Verka (Germany)

    2012-06-15

    Von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome with a variety of benign and malignant tumors such as retinal and central nervous system hemangioblastomas, endolymphatic sac tumors, renalcysts and tumors, pancreatic cysts and tumors, pheochromo-cytomas, and epididymal cystadenomas. Cross-sectional mo-dalities (computed tomography and magnetic resonance imaging) as well as ultrasound play a major role in the initial evaluation and follow-up of the various manifestations of VHL disease. Ga-68-labeled somatostatin receptor analogs already have a significant role in the diagnosis, staging, and therapy management of neuroendocrine neoplasms and neural crest tumors. Herein, we report a case presenting a variety of malignancies in VHL and showing the usefulness of Ga-68 somatostatin receptor PET/CT as a one-stop-shop imaging modality in the management of VHL disease.

  15. Ga-68 Somatostatin Receptor PET/CT in von Hippel-Lindau Disease

    International Nuclear Information System (INIS)

    Oh, Jong-Ryool; Min, Jung-Joon; Kulkarui, Harshad; Carreras, Cecilia; Schalch, Georg; Baum, Richard P.

    2012-01-01

    Von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome with a variety of benign and malignant tumors such as retinal and central nervous system hemangioblastomas, endolymphatic sac tumors, renalcysts and tumors, pancreatic cysts and tumors, pheochromo-cytomas, and epididymal cystadenomas. Cross-sectional mo-dalities (computed tomography and magnetic resonance imaging) as well as ultrasound play a major role in the initial evaluation and follow-up of the various manifestations of VHL disease. Ga-68-labeled somatostatin receptor analogs already have a significant role in the diagnosis, staging, and therapy management of neuroendocrine neoplasms and neural crest tumors. Herein, we report a case presenting a variety of malignancies in VHL and showing the usefulness of Ga-68 somatostatin receptor PET/CT as a one-stop-shop imaging modality in the management of VHL disease

  16. Somatostatin analogue scintigraphy and tuberculosis: case report

    International Nuclear Information System (INIS)

    Biancheri, I.; Rudenko, B.; Vautrin, P.; Raddoul, J.; Lamfichek, N.; Kantelip, B.; Mantion, G.

    2005-01-01

    Scintigraphy using a radiolabelled somatostatin analogue (111 In-pentetreotide) is useful in the detection of neuroendocrine tumors. But this radiopharmaceutical accumulates also in solid tumours or in inflammatory diseases such as granulomatosis. We present a case of 111 In-pentetreotide uptake in a tuberculous adenopathy. (author)

  17. Somatostatin receptor 2 knockout/lacZ knockin mice show impaired motor coordination and reveal sites of somatostatin action within the striatum.

    Science.gov (United States)

    Allen, Jeremy P; Hathway, Gareth J; Clarke, Neil J; Jowett, Mike I; Topps, Stephanie; Kendrick, Keith M; Humphrey, Patrick P A; Wilkinson, Lawrence S; Emson, Piers C

    2003-05-01

    The peptide somatostatin can modulate the functional output of the basal ganglia. The exact sites and mechanisms of this action, however, are poorly understood, and the physiological context in which somatostatin acts is unknown. Somatostatin acts as a neuromodulator via a family of five 7-transmembrane G protein-coupled receptors, SSTR1-5, one of which, SSTR2, is known to be functional in the striatum. We have investigated the role of SSTR2 in basal ganglia function using mice in which Sstr2 has been inactivated and replaced by the lacZ reporter gene. Analysis of Sstr2lacZ expression in the brain by beta-galactosidase histochemistry demonstrated a widespread pattern of expression. By comparison to previously published in situ hybridization and immunohistochemical data, Sstr2lacZ expression was shown to accurately recapitulate that of Sstr2 and thus provided a highly sensitive model to investigate cell-type-specific expression of Sstr2. In the striatum, Sstr2 expression was identified in medium spiny projection neurons restricted to the matrix compartment and in cholinergic interneurons. Sstr2 expression was not detected in any other nuclei of the basal ganglia except for a sparse number of nondopaminergic neurons in the substantia nigra. Microdialysis in the striatum showed Sstr2-null mice were selectively refractory to somatostatin-induced dopamine and glutamate release. In behavioural tests, Sstr2-null mice showed normal levels of locomotor activity and normal coordination in undemanding tasks. However, in beam-walking, a test of fine motor control, Sstr2-null mice were severely impaired. Together these data implicate an important neuromodulatory role for SSTR2 in the striatum.

  18. Pertussis toxin modifies the characteristics of both the inhibitory GTP binding proteins and the somatostatin receptor in anterior pituitary tumor cells

    International Nuclear Information System (INIS)

    Mahy, N.; Woolkalis, M.; Thermos, K.; Carlson, K.; Manning, D.; Reisine, T.

    1988-01-01

    The effects of pertussis toxin treatment on the characteristics of somatostatin receptors in the anterior pituitary tumor cell line AtT-20 were examined. Pertussis toxin selectively catalyzed the ADP ribosylation of the alpha subunits of the inhibitory GTP binding proteins in AtT-20 cells. Toxin treatment abolished somatostatin inhibition of forskolin-stimulated adenylyl cyclase activity and somatostatin stimulation of GTPase activity. To examine the effects of pertussis toxin treatment on the characteristics of the somatostatin receptor, the receptor was labeled by the somatostatin analog [125I]CGP 23996. [125I]CGP 23996 binding to AtT-20 cell membranes was saturable and within a limited concentration range was to a single high affinity site. Pertussis toxin treatment reduced the apparent density of the high affinity [125I]CGP 23996 binding sites in AtT-20 cell membranes. Inhibition of [125I]CGP 23996 binding by a wide concentration range of CGP 23996 revealed the presence of two binding sites. GTP predominantly reduced the level of high affinity sites in control membranes. Pertussis toxin treatment also diminished the amount of high affinity sites. GTP did not affect [125I]CGP 23996 binding in the pertussis toxin-treated membranes. The high affinity somatostatin receptors were covalently labeled with [125I] CGP 23996 and the photoactivated crosslinking agent n-hydroxysuccinimidyl-4-azidobenzoate. No high affinity somatostatin receptors, covalently bound to [125I]CGP 23996, were detected in the pertussis toxin-treated membranes. These results are most consistent with pertussis toxin uncoupling the inhibitory G proteins from the somatostatin receptor thereby converting the receptor from a mixed population of high and low affinity sites to only low affinity receptors

  19. Radioimmunoassay for 6-D-tryptophan analog of luteinizing hormone-releasing hormone: measurement of serum levels after administration of long-acting microcapsule formulations

    International Nuclear Information System (INIS)

    Mason-Garcia, M.; Vigh, S.; Comaru-Schally, A.M.; Redding, T.W.; Somogyvari-Vigh, A.; Horvath, J.; Schally, A.V.

    1985-01-01

    A sensitive and specific radioimmunoassay for [6-D-tryptophan]luteinizing hormone-releasing hormone ([D-Trp 6 ]LH-RH) was developed and used for following the rate of liberation of [D-Trp 6 ]LH-RH from a long-acting delivery systems based on a microcapsule formulation. Rabbit antibodies were generated against [D-Trp 6 ]LH-RH conjugated to bovine serum albumin with glutaraldehyde. Crossreactivity with LH-RH was less than 1%; there was no significant cross-reactivity with other peptides. The minimal detectable dose of [D-Trp 6 ]LH-RH was 2 pg per tube. In tra- and interassay coefficients of variation were 8% and 10%, respectively. The radioimmunoassay was suitable for direct determination of [D-Trp 6 ]LH-RH in serum, permitting the study of blood levels of the analog after single injections into normal men and after one-a-month administration of microcapsules to rats. In men, 90 min after subcutaneous injection of 250 μg of the peptide, serum [D-Trp 6 ]LH-RH rose to 6-12 ng/ml. Luteinizing hormone was increased 90 min and 24 hr after the administration of the analog. Several batches of microcapsules were tested in rats and the rate of release of [D-Trp 6 ]LH-RH was followed. The improved batch of microcapsules of [D-Trp 6 ]LH-RH increased serum concentrations of the analog for 30 days or longer after intramuscular injection

  20. Purification of a putative brain somatostatin receptor

    International Nuclear Information System (INIS)

    He, Haitao; Johnson, K.; Thermos, K.; Reisine, T.

    1989-01-01

    The brain somatostatin receptor was purified by affinity chromatographic techniques. A protein of 60 kDa could be purified from rat brain. The protein was eluted from a [D-Trp 8 ]SRIF affinity column with either sodium acetate (pH 5.5) or free [D-Trp 8 ]SRIF. The binding of the protein to the affinity column was prevented by free [D-Trp 8 ]SRIF or the stable SRIF analogue SMS 201-996 but not by the inactive somatostatin 28-(1-14). The purified receptor could be covalently labeled by the 125 I-labeled SRIF analogue CGP 23996. Excess [D-Trp 8 ]SRIF blocked the binding of 125 I-labeled CGP 23996 to the purified receptor, but somatostatin 28-(1-14) did not affect the binding. A 60-kDa protein was also purified from the anterior pituitary cell line AtT-20, which has a high expression of SRIF receptors. In contrast, no 60-kDa protein could be purified from CHO cells, which have no detectable SRIF receptors. These findings present evidence for the purification of the SRIF receptor

  1. Targeting either GH or IGF-I during somatostatin analogue treatment in patients with acromegaly

    DEFF Research Database (Denmark)

    Dal, Jakob; Klose, Marianne; Heck, Ansgar

    2018-01-01

    CONTEXT: Discordant GH and IGF-I values are frequent in acromegaly. The clinical significance and its dependence on treatment modality and of glucose-suppressed GH (GHnadir) measurements remain uncertain. OBJECTIVE: To evaluate the effects of targeting either IGF-I or GH during somatostatin analog...... (SA) treatment. PATIENTS AND METHODS: 84 patients with controlled acromegaly after surgery (n=23) or SA (n=61) underwent a GH-profile including an OGTT, at baseline and after 12 months. SA patients were randomized to monitoring according to either IGF-I (n= 33) or GHnadir (n=28). SA dose escalation...

  2. 99Tcm labelling and in vitro binding of dextran-somatostatin conjugate

    International Nuclear Information System (INIS)

    Cui Haiping; China Inst. of Atomic Energy, Beijing; Zhai Shizhen; Du Jin; Beijing Univ., Beijing

    2006-01-01

    Natural somatostatin and dextran-20 are used to synthesis somatostatin-dextran (SMS-Dx 20 ). The in vitro somatostatin receptor competition binding study of somatostatin-dextran is carried out by using rate brain cortex membranes (express somatostatin receptor type 2) and 125 I-Tyr 3 -Octreotide as a radioligand. The somatostatin-dextran conjugate is then labelled with 99 Tc m using SnCl 2 as reduce agent and tested for its in vitro binding properties. The somatostatin-dextran conjugate shows high somatostatin receptor binding affinity, i.e. in the same IC 50 value as the reference ligand Octreotide (IC 50 ∼5.95 nmol/L). The labelling efficiency is more than 85%. The specific binding of 99 Tc m labeled somatostatin-dextran conjugate is 25%-40%. The somatostatin-dextran conjugate is worthy of further investigation for 99 Tc m radiolabeling with diagnostic possibilities for somatostatin receptor positive tumors. (authors)

  3. Somatostatin receptor imaging in intracranial tumours

    International Nuclear Information System (INIS)

    Schmidt, M.; Scheidhauer, K.; Voth, E.; Schicha, H.; Luyken, C.; Hildebrandt, G.; Klug, N.

    1998-01-01

    The somatostatin analogue [ 111 In-DTPA-d-Phe 1 ]-octreotide ( 111 In-octreotide) allows scintigraphic visualization of somatostatin receptor-expressing tissue. While it is well known that a large variety of tissues express somatostatin receptors and 111 In-octreotide scintigraphy has a clearly defined role in various neuroendocrine diseases, the clinical value of 111 In-octreotide scintigraphy in brain tumours is still under clinical investigation. In 124 patients with 141 brain lesions (63 meningiomas, 24 pituitary adenomas, 10 gliomas WHO class I and II, 12 gliomas WHO class III and IV, 11 neurinomas and 2 neurofibromas, 7 metastases and 12 other varieties: three non-Hodgkin B-cell lymphomas, two epidermoids, one abscess, one angioleiomyoma, one chordoma, one haemangiopericytoma, one osteosarcoma, one plasmacytoma and one pseudocyst), 111 In-octreotide scintigraphy was performed 4-6 and 24 h after i.v. injection of 110-220 MBq 111 In-octreotide. Planar images of the head in four views with a 128 x 128 matrix and single-photon emission tomographic images (64 x 64 matrix) were acquired, and lesions were graded according to qualitative tracer uptake. Fifty-nine of the 63 meningiomas showed moderate to intense tracer uptake. Nine of 24 pituitary adenomas were visible; the remaining 15 did not show any tracer uptake. None of the class I and II gliomas with an intact blood-brain barrier were detected whereas 11/12 class III and IV gliomas showed 111 In-octreotide uptake. None of the neurinomas or neurofibromas were positive. Five of seven metastases were classified as positive, as were the osteosarcoma, two of three non-Hodgkin B-cell lymphomas, one abscess, one angioleiomyoma, one chordoma and one haemangiopericytoma. The other varieties (one non-Hodgkin B-cell lymphoma, two epidermoids, one plasmacytoma and one pseudocyst) did not show 111 In-octreotide uptake. The results demonstrate that a large variety of intracranial lesions express somatostatin receptors and

  4. Somatostatin receptor imaging in intracranial tumours

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, M.; Scheidhauer, K.; Voth, E.; Schicha, H. [Department of Nuclear Medicine, University of Koeln (Germany); Luyken, C.; Hildebrandt, G.; Klug, N. [Department of Neurosurgery, University of Kolen (Germany)

    1998-07-01

    The somatostatin analogue [{sup 111}In-DTPA-d-Phe{sup 1}]-octreotide ({sup 111}In-octreotide) allows scintigraphic visualization of somatostatin receptor-expressing tissue. While it is well known that a large variety of tissues express somatostatin receptors and {sup 111}In-octreotide scintigraphy has a clearly defined role in various neuroendocrine diseases, the clinical value of {sup 111}In-octreotide scintigraphy in brain tumours is still under clinical investigation. In 124 patients with 141 brain lesions (63 meningiomas, 24 pituitary adenomas, 10 gliomas WHO class I and II, 12 gliomas WHO class III and IV, 11 neurinomas and 2 neurofibromas, 7 metastases and 12 other varieties: three non-Hodgkin B-cell lymphomas, two epidermoids, one abscess, one angioleiomyoma, one chordoma, one haemangiopericytoma, one osteosarcoma, one plasmacytoma and one pseudocyst), {sup 111}In-octreotide scintigraphy was performed 4-6 and 24 h after i.v. injection of 110-220 MBq {sup 111}In-octreotide. Planar images of the head in four views with a 128 x 128 matrix and single-photon emission tomographic images (64 x 64 matrix) were acquired, and lesions were graded according to qualitative tracer uptake. Fifty-nine of the 63 meningiomas showed moderate to intense tracer uptake. Nine of 24 pituitary adenomas were visible; the remaining 15 did not show any tracer uptake. None of the class I and II gliomas with an intact blood-brain barrier were detected whereas 11/12 class III and IV gliomas showed {sup 111}In-octreotide uptake. None of the neurinomas or neurofibromas were positive. Five of seven metastases were classified as positive, as were the osteosarcoma, two of three non-Hodgkin B-cell lymphomas, one abscess, one angioleiomyoma, one chordoma and one haemangiopericytoma. The other varieties (one non-Hodgkin B-cell lymphoma, two epidermoids, one plasmacytoma and one pseudocyst) did not show {sup 111}In-octreotide uptake. The results demonstrate that a large variety of intracranial

  5. Immuno-reactive somatostatin in the cerebro-spinal fluid

    International Nuclear Information System (INIS)

    Kohler, J.

    1983-01-01

    In the present work the lumbar cerebro-spinal fluid of 178 patients with different neurological affections was examined with the aid of a specific radioimmunoassay for somatostatin. 18 patients without any pathologic neurological findings served as controls. In degenerative diseases of the brain, reduced somatostatin levels in the cerebro-spinal fluid as compared to the controls were measured. In 3 patients with isolated cerebellar atrophy no reduction of the somatostatin content was found; rather the values were highly normal. Huntington-Chorea also is a case apart. In patients with manifest affections, the somatostatin reduction, amounting to 54.6%, was particularly notable as compared to the controls. By contrast, degenerative diseases with predominant medullary and spastic affection are characterized by significantly increased somatostatin levels. Again, in non-spastic patients the values were not significantly different from those of the controls. Patients with inflammations of the brain and meminges as well as with tumors of the nervous system showed somatostatin levels increased by about 60.8% respectively 51.8% as compared to the controls. Epileptic patients normally exhibit a reduced somatostatin level in the cerebro-spinal fluid, but the reduction is not significant. Disseminated encephalomyclitis, whether chromic or acute, is not found to be associated with significant modifications of the somatostatin level in the cerebro-spinal fluid. Strikingly, however, patients in which the disease took a serious or very serious clinical course showed also the lowest somatostatin levels in the cerebro-spinal fluid. In patients exhibiting the roof compression symptom in consequence of a prolapse of the disk, no significant modifications were found. By contrast, in patients with the symptoms of a transverse lesion, significantly increased somatostatin values were measured. (orig./MG) [de

  6. Somatostatin-Immunoreactive Pancreaticoduodenal Neuroendocrine Neoplasms

    DEFF Research Database (Denmark)

    Engelund Luna, Iben; Monrad, Nina; Binderup, Tina

    2016-01-01

    , and biochemical features as well as treatment and prognosis. DESIGN: Twenty-three patients with p-dSOM (9 duodenal, 12 pancreatic, 2 unknown primary tumour) were identified from our prospective neuroendocrine tumour (NET) database, and data according to the study aims were recorded. RESULTS: Of the 9 patients...... with duodenal SOM the m/f ratio was 4/5. All males and one female had NF-1. Seven patients had stage 1A-B and 2 had stage 2B disease. The Ki-67 index was 1-5% (median 2%). Plasma somatostatin was elevated in patients with 2B disease. Of the 14 patients with pancreatic SOM or unknown primary tumour the m/f ratio...... was 2/12. One male had MEN-1. Five had stage 1A-2B and nine had stage 4. The Ki-67 index was 1-40% (median 7%). Plasma somatostatin was elevated in seven patients. Patients reported symptoms related to the somatostatinoma syndrome, but none fulfilled the criteria for a full syndrome. Primary tumour...

  7. Development of 99mTc labelled somatostatin analogues with high affinity for somatostatin receptors

    International Nuclear Information System (INIS)

    Maina, T.; Nock, B.; Nicolopoulou, A.; Tsipra, C.; Poppe, M.; Chiotellis, E.

    2001-01-01

    A recent development in oncology involves the use of metabolically stabilized peptide hormone analogues labelled with metallic radionuclides for the diagnosis or therapy of malignant disease. This approach was successfully applied for the first time in the visualization of somatostatin positive tumours and their metastases with 111 In DTPA-octreotide. In an effort to obtain a 99m Tc somatostatin receptor affine radioligand we describe herein the synthesis, radiochemistry and preliminary biological evaluation of two novel 99m Tc labelled somatostatin analogues, N 4 -TOC and N 4 -RC-160. In these compounds a tetraamine bifunctional unit was covalently attached to the N-terminal (D)Phe 1 of the peptide chain using Boc-protection strategies. The peptide conjugates were purified by high performance liquid chromatography (HPLC) and characterized by UV/Vis and ES-MS spectroscopies. As revealed by HPLC, 99m Tc labelling was quantitative under mild conditions, leading to a single 99m Tc species in high specific activities. Affinity of 99m Tc N 4 -TOC for the somatostatin receptor, as determined by in vitro binding assays in rat brain cortex membranes, was found unaffected by the presence of the bulky metal chelate. The binding properties of 99m Tc N 4 -RC-160 could not be determined by this assay due to an extremely high non-specific binding of this radioligand, and will be shortly investigated by other methods. Tissue distribution in healthy mice revealed that 99m Tc N 4 -TOC is clearing mainly through the kidneys and the urinary tract whereas 99m Tc N 4 -RC-160 shows a high accumulation in the liver as a result of its lipophilicity. Analysis of urine samples by HPLC showed that 99m Tc N 4 -TOC is excreted integer from the body of mice, while 99m Tc N 4 -RC-160 is totally transformed to an unidentified hydrophilic metabolite in vivo. The location of this metabolism is currently investigated. In vivo blocking experiments using animals pre-treated with 50 μg octreotide

  8. Analog computing

    CERN Document Server

    Ulmann, Bernd

    2013-01-01

    This book is a comprehensive introduction to analog computing. As most textbooks about this powerful computing paradigm date back to the 1960s and 1970s, it fills a void and forges a bridge from the early days of analog computing to future applications. The idea of analog computing is not new. In fact, this computing paradigm is nearly forgotten, although it offers a path to both high-speed and low-power computing, which are in even more demand now than they were back in the heyday of electronic analog computers.

  9. Receptor binding of somatostatin-14 and somatostatin-28 in rat brain: differential modulation by nucleotides and ions.

    Science.gov (United States)

    Srikant, C B; Dahan, A; Craig, C

    1990-02-04

    The tissue-selective binding of the two principal bioactive forms of somatostatin, somatostatin-14 (SS-14) and somatostatin-28 (SS-28), their ability to modulate cAMP-dependent and -independent regulation of post-receptor events to different degrees and the documentation of specific labelling of SS receptor subtypes with SS-28 but not SS-14 in discrete regions of rat brain suggest the existence of distinct SS-14 and SS-28 binding sites. Receptor binding of SS-14 ligands has been shown to be modulated by nucleotides and ions, but the effect of these agents on SS-28 binding has not been studied. In the present study we investigated the effects of adenine and guanine nucleotides as well as monovalent and divalent cations on rat brain SS receptors quantitated with radioiodinated analogs of SS-14 ([125I-Tyr11]SS14, referred to in this paper as SS-14) and SS-28 ([Leu8, D-Trp22, 125I-Tyr25] SS-28, referred to as LTT* SS-28) in order to determine if distinct receptor sites for SS-14 and SS-28 could be distinguished on the basis of their modulation by nucleotides and ions. GTP as well as ATP exerted a dose-dependent inhibition (over a concentration range of 10(-7)-10(-3) M) of the binding of the two radioligands. The nucleotide inhibition of binding resulted in a decrease the Bmax of the SS receptors, the binding affinity remaining unaltered. GTP (10(-4) M) decreased the Bmax of LTT* SS-28 binding sites to a greater extent than ATP (145 +/- 10 and 228 +/- 16 respectively, compared to control value of 320 +/- 20 pmol mg-1). Under identical conditions GTP was less effective than ATP in reducing the number of T* SS-14 binding sites (Bmax = 227 +/- 8 and 182 +/- 15, respectively, compared to 340 +/- 15 pmol mg-1 in the absence of nucleotides). Monovalent cations inhibited the binding of both radioligands, Li+ and Na+ inhibited the binding of T* SS-14 to a greater extent than K+. The effect of divalent cations on the other hand was varied. At low concentration (2 mM) Mg2+, Ba2

  10. Comparison of vials and prefilled pens of a rapid-acting insulin analog on pharmacy budgets in a long-term care setting.

    Science.gov (United States)

    Eby, Elizabeth L; Smolen, Lee J; Pitts, Amber C; Krueger, Linda A; Andrews, Jeffrey Scott

    2014-12-01

    Estimate budgetary impact for skilled nursing facility converting from individual patient supply (IPS) delivery of rapid-acting insulin analog (RAIA) 10-mL vials or 3-mL prefilled pens to 3-mL vials. A budget-impact model used insulin volume purchased and assumptions of length of stay (LOS), daily RAIA dose, and delivery protocol to estimate the cost impact of using 3-mL vials. Skilled nursing facility. Medicare Part A patients. Simulations conducted using 12-month current and future scenarios. Comparisons of RAIA use for 13- and 28-day LOS. RAIA costs and savings, waste reduction. For patients with 13-day LOS using 20 units/day of IPS insulin, the model estimated a 70% reduction in RAIA costs and units purchased and a 95% waste reduction for the 3-mL vial compared with the 10-mL vial. The estimated costs for prefilled pen use were 58% lower than for use of 10-mL vials. The incremental savings associated with 3-mL vial use instead of prefilled pens was 28%, attributable to differences in per-unit cost of insulin in vials versus prefilled pens. Using a more conservative scenario of 28-day LOS at 20 units/day, the model estimated a 40% reduction in RAIA costs and units purchased, resulting in a 91% reduction in RAIA waste for the 3-mL vial, compared with 10-mL vial. Budget-impact analysis of conversion from RAIA 10-mL vials or 3-mL prefilled pens to 3-mL vials estimated reductions in both insulin costs and waste across multiple scenarios of varying LOS and patient daily doses for skilled nursing facility stays.

  11. Study of somatostatin in simple obesity

    Energy Technology Data Exchange (ETDEWEB)

    Abdel-Hafez, M A; El-Ghazaly, S; El-Feky, N A; Sayed, S N [Cairo Univ. (Egypt)

    1990-02-01

    C-peptide, as a marker for pancreatic beta cells function, and somatostatin (SS) in plasma of obese males (n = 15) and a corresponding normal weight control subjects (n = 10) are studied. Fasting plasma SS and serum C-peptide are significantly higher in obese vs lean group. This can be explained by hypertrophy of both D- and B-cells of the pancreatic islets reported by other investigators. Post-prandial plasma SS is insignificantly increased in obese vs the control group whereas the increase in C-peptide levels is significant suggesting unequal response of B- and D-cells to meal in the obese group. It is concluded that circulating SS may play an important role in the development if obesity. Hyperinsulinaemia documented in obesity may be due to hypersecretion of insulin. That may contribute to increased somatomedin-C in obesity. (author).

  12. Study of somatostatin in simple obesity

    International Nuclear Information System (INIS)

    Abdel-Hafez, M.A.; El-Ghazaly, S.; El-Feky, N.A.; Sayed, S.N.

    1990-01-01

    C-peptide, as a marker for pancreatic beta cells function, and somatostatin (SS) in plasma of obese males (n = 15) and a corresponding normal weight control subjects (n = 10) are studied. Fasting plasma SS and serum C-peptide are significantly higher in obese vs lean group. This can be explained by hypertrophy of both D- and B-cells of the pancreatic islets reported by other investigators. Post-prandial plasma SS is insignificantly increased in obese vs the control group whereas the increase in C-peptide levels is significant suggesting unequal response of B- and D-cells to meal in the obese group. It is concluded that circulating SS may play an important role in the development if obesity. Hyperinsulinaemia documented in obesity may be due to hypersecretion of insulin. That may contribute to increased somatomedin-C in obesity. (author)

  13. Somatostatin receptor scintigraphy on thyroid carcinoma

    International Nuclear Information System (INIS)

    Pan Weimin; Tan Tianzhi

    2004-01-01

    Purpose: To study the diagnostic value and clinical method of somatostatin receptor scintigraphy on thyroid carcinoma using 99 Tc m -RC-160 labeled with direct method as scintigraphy reagent; Methods: Somatostatin receptor scintigraphy (SRS) were performed on 25 patients with thyroid carcinoma, using 99 Tc m -RC-160 labeled with direct method as scintigraphy reagent, controlling with 131 I- whole- body- imaging(1312 -WBI). Results: Of 4 patients with MTC (medullary thyroid carcinoma), positive metastasis and primary tumour were detected on 3 patients by SRS, negative results were obtained by 131 I-WBI, the positive detective rate by SRS is 3/4; of 12 patients with PTC (papillary thyroid carcinoma), positive metastasis and primary tumour were detected on 2 patients by SRS or 131 I-WBI,1 of which only by SRS, while negative results were obtained by 131 I- WBI, the positive detective rate by SRS is 3/12; of 8 patients with FTC(follicular thyroid carcinoma), positive metastasis and primary tumour were detected on 1 patients by SRS or 131 I-WBI, and 2 positive results were obtained only by SRS, while negative by 131 I-WBI, the positive detective rate by SRS is 3/8; of 1 patients with HCC (hurthle cell carcinoma ), positive metastasis and primary tumour were detected by SRS, while negative by 131 I-WBI; Conclusions: SRS using 99 Tc m -RC-160 labeled with direct method as scintigraphy reagent has high diagnostic value on thyroid carcinoma, especially on MTC and HCC. (authors)

  14. Breast cancer imaging using radiolabelled somatostatin analogues

    International Nuclear Information System (INIS)

    Dalm, Simone U.; Melis, Marleen; Emmering, Jasper; Kwekkeboom, Dik J.; Jong, Marion de

    2016-01-01

    Imaging and therapy using radiolabelled somatostatin analogues are methods successfully used in patients with somatostatin receptor (SSTR)-expressing neuroendocrine tumours. Since these techniques were first introduced, many improvements have been made. SSTR expression has also been reported on breast cancer (BC). Currently mammography, magnetic resonance imaging and ultrasound are the most frequent methods used for BC imaging. Since SSTR expression on BC was demonstrated, clinical studies examining the feasibility of visualizing primary BC using SSTR radioligands have been performed. However, to date SSTR-mediated nuclear imaging is not used clinically in BC patients. The aim of this review is to assess whether recent improvements made within nuclear medicine may enable SSTR-mediated imaging to play a role in BC management. For this we critically analysed results of past studies and discussed the potential of the improvements made within nuclear medicine on SSTR-mediated nuclear imaging of BC. Seven databases were searched for publications on BC imaging with SSTR radioligands. The papers found were analysed by 3 individual observers to identify whether the studies met the pre-set inclusion criteria defined as studies in which nuclear imaging using radiolabelled SST analogues was performed in patients with breast lesions. Twenty-four papers were selected for this review including studies on SSTR-mediated nuclear imaging in BC, neuroendocrine BC and other breast lesions. The analysed studies were heterogeneous with respect to the imaging method, imaging protocol, patient groups and the radiolabelled SST analogues used. Despite the fact that the analysed studies were heterogeneous, sensitivity for primary BC ranged from 36–100%. In a subset of the studies LN lesions were visualized, but sensitivity was lower compared to that for primary tumours. A part of the studies included benign lesions and specificity ranged from 22–100%. Furthermore, false negatives and

  15. Studies on mRNA expression of the somatostatin receptor family in lung cancer

    International Nuclear Information System (INIS)

    Wang Jing; Deng Jinglan; Wu Shengxi; Qiao Hongqing

    2000-01-01

    Objective: To investigate the characteristics of expression and distribution of 5 subtypes of somatostatin receptors (SSTR1∼5) in lung cancer. Methods: With [α- 35 S]dATP labelled oligonucleotides of the 5 SSTR subtypes as probes, using in situ hybridization, patterns of mRNA expression were detected in lung cancer tissue sections of 21 cases which fell in varied pathologic types. Additionally, Leica Q-500 image analyzing device was employed to semi-quantitatively analyze density of the expression. Results: Patterns of SSTR1∼5 expression in lung cancer were as follows: SSTR2 expression was dominant in small cell lung cancer (SCLC) while in non-small cell lung cancer (NSCLC) such as adenous and squamous, SSTR1 expression was stronger than that of the other 4 subtypes, In density of SSTR1∼5 expression in lung cancer, NSCLC was higher than SCLC (P<0.01). Conclusions: even though patterns and density of expression of SSTR subtypes in the lung cancer showed heterogeneity in different histopathologic types, as in SCLC and in NSCLC. Therefore, it has positive prospects for somatostatin analog-oriented agents to be used in treatment of both types of the lung cancers

  16. Expression of the somatostatin receptor family mRNAs in lung cancer

    International Nuclear Information System (INIS)

    Wang Jing; Wang Liangang; Deng Jinglan; Wu Shengxi

    2000-01-01

    To investigate the characteristics of expression and distribution of 5 subtypes of somatostatin receptors (SSTR1-5) in lung cancer, in situ hybridization was used to examine the expression patterns of SSTR mRNAs in 21 cases of different pathologic types of lung cancer tissues with [α- 35 S]dATP labelled oligonucleotides of the 5 SSTR subtypes as probes. Additionally, Leica Q-500 image analysis processing system was employed for the semi-quantitatively analysis of the hybridization signals. Patterns of SSTR1-5 expression in lung cancer tissues were found as follows. SSTR2 was prominent in small cell lung cancer (SCLC), whereas in non-small cell lung cancer (NSCLC) including the adenous cancer (Ad) and the squamous cancer (Sq), the expression of SSTR1 mRNA was stronger than that of the other 4 types. the expression density of SSTR1-5 in the NSCLC was higher that the SCLC (p < 0.01). The expression patterns and densities of the SSTR subtypes showed heterogeneity in different pathologic types of lung cancer. The expressions of the SSTR mRNAs in both SCLC and NSCLC indicated the positive prospects for somatostatin analog (SSA)-oriented agents in the treatment of both types of the lung cancer

  17. Analog earthquakes

    International Nuclear Information System (INIS)

    Hofmann, R.B.

    1995-01-01

    Analogs are used to understand complex or poorly understood phenomena for which little data may be available at the actual repository site. Earthquakes are complex phenomena, and they can have a large number of effects on the natural system, as well as on engineered structures. Instrumental data close to the source of large earthquakes are rarely obtained. The rare events for which measurements are available may be used, with modfications, as analogs for potential large earthquakes at sites where no earthquake data are available. In the following, several examples of nuclear reactor and liquified natural gas facility siting are discussed. A potential use of analog earthquakes is proposed for a high-level nuclear waste (HLW) repository

  18. The Inhibitory Effect of Somatostatin Receptor Activation on Bee Venom-Evoked Nociceptive Behavior and pCREB Expression in Rats

    Directory of Open Access Journals (Sweden)

    Li Li

    2014-01-01

    Full Text Available The present study examined nociceptive behaviors and the expression of phosphorylated cAMP response element-binding protein (pCREB in the dorsal horn of the lumbar spinal cord and the dorsal root ganglion (DRG evoked by bee venom (BV. The effect of intraplantar preapplication of the somatostatin analog octreotide on nociceptive behaviors and pCREB expression was also examined. Subcutaneous injection of BV into the rat unilateral hindpaw pad induced significant spontaneous nociceptive behaviors, primary mechanical allodynia, primary thermal hyperalgesia, and mirror-thermal hyperalgesia, as well as an increase in pCREB expression in the lumbar spinal dorsal horn and DRG. Octreotide pretreatment significantly attenuated the BV-induced lifting/licking response and mechanical allodynia. Local injection of octreotide also significantly reduced pCREB expression in the lumbar spinal dorsal horn and DRG. Furthermore, pretreatment with cyclosomatostatin, a somatostatin receptor antagonist, reversed the octreotide-induced inhibition of the lifting/licking response, mechanical allodynia, and the expression of pCREB. These results suggest that BV can induce nociceptive responses and somatostatin receptors are involved in mediating the antinociception, which provides new evidence for peripheral analgesic action of somatostatin in an inflammatory pain state.

  19. Novel Somatostatin Receptor Ligands Therapies for Acromegaly

    Directory of Open Access Journals (Sweden)

    Rosa Maria Paragliola

    2018-03-01

    Full Text Available Surgery is considered the treatment of choice in acromegaly, but patients with persistent disease after surgery or in whom surgery cannot be considered require medical therapy. Somatostatin receptor ligands (SRLs octreotide (OCT, lanreotide, and the more recently approved pasireotide, characterized by a broader receptor ligand binding profile, are considered the mainstay in the medical management of acromegaly. However, in the attempt to offer a more efficacious and better tolerated medical approach, recent research has been aimed to override some limitations related to the use of currently approved drugs and novel SRLs therapies, with potential attractive features, have been proposed. These include both new formulation of older molecules and new molecules. Novel OCT formulations are aimed in particular to improve patients’ compliance and to reduce injection discomfort. They include an investigational ready-to-use subcutaneous depot OCT formulation (CAM2029, delivered via prefilled syringes and oral OCT that uses a “transient permeability enhancer” technology, which allows for OCT oral absorption. Another new delivery system is a long-lasting OCT implant (VP-003, which provide stable doses of OCT throughout a period of several months. Finally, a new SRL DG3173 (somatoprim seems to be more selective for GH secretion, suggesting possible advantages in the presence of hyperglycemia or diabetes. How much these innovations will actually be beneficial to acromegaly patients in real clinical practice remains to be seen.

  20. Basal Forebrain Gating by Somatostatin Neurons Drives Prefrontal Cortical Activity.

    Science.gov (United States)

    Espinosa, Nelson; Alonso, Alejandra; Morales, Cristian; Espinosa, Pedro; Chávez, Andrés E; Fuentealba, Pablo

    2017-11-17

    The basal forebrain provides modulatory input to the cortex regulating brain states and cognitive processing. Somatostatin-expressing neurons constitute a heterogeneous GABAergic population known to functionally inhibit basal forebrain cortically projecting cells thus favoring sleep and cortical synchronization. However, it remains unclear if somatostatin cells can regulate population activity patterns in the basal forebrain and modulate cortical dynamics. Here, we demonstrate that somatostatin neurons regulate the corticopetal synaptic output of the basal forebrain impinging on cortical activity and behavior. Optogenetic inactivation of somatostatin neurons in vivo rapidly modified neural activity in the basal forebrain, with the consequent enhancement and desynchronization of activity in the prefrontal cortex, reflected in both neuronal spiking and network oscillations. Cortical activation was partially dependent on cholinergic transmission, suppressing slow waves and potentiating gamma oscillations. In addition, recruitment dynamics was cell type-specific, with interneurons showing similar temporal profiles, but stronger responses than pyramidal cells. Finally, optogenetic stimulation of quiescent animals during resting periods prompted locomotor activity, suggesting generalized cortical activation and increased arousal. Altogether, we provide physiological and behavioral evidence indicating that somatostatin neurons are pivotal in gating the synaptic output of the basal forebrain, thus indirectly controlling cortical operations via both cholinergic and non-cholinergic mechanisms. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Deficiencies in fat-soluble vitamins in long-term users of somatostatin analogue

    NARCIS (Netherlands)

    Fiebrich, H. -B.; van den Berg, G.; Kema, I. P.; Links, T. P.; Kleibeuker, J. H.; van Beek, A. P.; Walenkamp, A. M. E.; Sluiter, W. J.; de Vries, E. G. E.

    2010-01-01

    P>Background Somatostatin analogues are administered to control hormone hypersecretion in acromegaly and carcinoid patients. Somatostatin analogues can increase fat in the stools, which can lead to loss of fat-soluble vitamins. The effect of long-term somatostatin analogue use on vitamin levels

  2. Somatostatin-like peptide and regeneration capacities in planarians.

    Science.gov (United States)

    Bautz, A; Schilt, J

    1986-11-01

    The presence of a neuropeptide immunologically related to somatostatin (SRIF) has been investigated in the neurosecretory cells of two regenerating planarian species (Dugesia lugubris and Dendrocoelum lacteum). A correlation has been shown between the discharge of the SRIF-like-immunoreactive cells during the first hours after amputation and the capacity to regenerate, and between the persistence of numerous positive cells and the lack of regeneration. These results suggest that somatostatin might play a regulatory (inhibitory) role on the cellular proliferation which leads to the blastema edification.

  3. Somatostatin receptor-mediated imaging and therapy: basic science, current knowledge, limitations and future perspectives

    Energy Technology Data Exchange (ETDEWEB)

    Breeman, W.A.P.; Jong, M. de; Kwekkeboom, D.J.; Valkema, R.; Bakker, W.H.; Kooij, P.P.M. [Dept. of Nuclear Medicine, Erasmus Medical Centre Rotterdam (Netherlands); Visser, T.J. [Dept. of Internal Medicine, Erasmus Medical Centre Rotterdam (Netherlands); Krenning, E.P. [Dept. of Nuclear Medicine, Erasmus Medical Centre Rotterdam (Netherlands); Dept. of Internal Medicine, Erasmus Medical Centre Rotterdam (Netherlands)

    2001-09-01

    In vivo somatostatin receptor-mediated scintigraphy has proven to be a valuable method for the visualisation of neuroendocrine tumours and their metastases. A new application is the use of radiolabelled analogues for somatostatin receptor-mediated therapy. This paper presents a review on the basic science, historical background and current knowledge of somatostatin receptor subtypes and their expression in neuroendocrine tumours. New somatostatin analogues, new chelators, ''new'' radionuclides and combinations thereof are also discussed. Due attention is given to limitations and future perspectives of somatostatin receptor-mediated imaging and therapy. (orig.)

  4. Somatostatin receptor-mediated imaging and therapy: basic science, current knowledge, limitations and future perspectives

    International Nuclear Information System (INIS)

    Breeman, W.A.P.; Jong, M. de; Kwekkeboom, D.J.; Valkema, R.; Bakker, W.H.; Kooij, P.P.M.; Visser, T.J.; Krenning, E.P.

    2001-01-01

    In vivo somatostatin receptor-mediated scintigraphy has proven to be a valuable method for the visualisation of neuroendocrine tumours and their metastases. A new application is the use of radiolabelled analogues for somatostatin receptor-mediated therapy. This paper presents a review on the basic science, historical background and current knowledge of somatostatin receptor subtypes and their expression in neuroendocrine tumours. New somatostatin analogues, new chelators, ''new'' radionuclides and combinations thereof are also discussed. Due attention is given to limitations and future perspectives of somatostatin receptor-mediated imaging and therapy. (orig.)

  5. Regulation of somatostatin release in the nervous system of the rat

    International Nuclear Information System (INIS)

    Sheppard, M.

    1979-08-01

    This thesis represents the work done to study the release of somatostatin from the rat central nervous system in vitro, providing some evidence for a physiological role for somatostatin. Somatostatin was measured by a sensitive and specific radioimmunoassay devoloped in the laboratory. Chapter 2 reviews the literature on hypothalamic peptides and control of an anterior pituitary function, somatostatin, other central nervous system peptides and neurosecretion. Chapter 3 describes the central nervous system tissue dissection technique, the radioimmunoassay for somatostatin and the tissue levels of somatostatin immunoreactivity in different areas of the central nervous system. Chapter 4 deals with the release of immunoreactive somatostatin from incubated rat hypothalamus in vitro and the influence of other hormones and neuropeptides on this release. Chapter 5 describes the preparation of isolated nerve endings (synaptosomes) from four different areas of rat brain, the localisation of somatostatin to the synaptosome fraction of brain homogenates and the release of somatostatin from these synaptosomes. Chapter 6 deals with the release of somatostatin from incubated rat spinal cord in vitro. Chapter 7 presents the results of the characterisation of released immunoreactive material, the technique utilised being serial dilution of immunoreactive material and comparison to the standard curve, Sephadex gel chromatography, affinity chromatography, and the effect of released immunoreactive somatostatin on growth hormone release from perifused hemipituitaries in vitro, i.e. biological activity. Chapter 8 provides a summary of the main conclusions reached in this study and is followed by the Appendix describing chemical and biochemical methods, histological techniques, and statistical methods

  6. How Analogy Drives Physics

    International Nuclear Information System (INIS)

    Hofstadter, Doug

    2004-01-01

    Many new ideas in theoretical physics come from analogies to older ideas in physics. For instance, the abstract notion of 'isospin' (or isotopic spin) originated in the prior concept of 'spin' (quantized angular momentum); likewise, the concept of 'phonon' (quantum of sound, or quantized collective excitation of a crystal) was based on the prior concept of 'photon' (quantum of light, or quantized element of the electromagnetic field). But these two examples, far from being exceptions, in fact represent the bread and butter of inventive thinking in physics. In a nutshell, intraphysics analogy-making -- borrowing by analogy with something already known in another area of physics -- is central to the progress of physics. The aim of this talk is to reveal the pervasiveness -- indeed, the indispensability -- of this kind of semi-irrational, wholly intuitive type of thinking (as opposed to more deductive mathematical inference) in the mental activity known as 'doing physics'. Speculations as to why wild analogical leaps are so crucial to the act of discovery in physics (as opposed to other disciplines) will be offered.

  7. Somatostatin receptor scintigraphy in patients with cat-scratch disease

    International Nuclear Information System (INIS)

    Krause, R.; Schnedl, W.J.; Hoier, S.; Piswanger-Soelkner, C.; Lipp, R.W.; Daxboeck, F.; Reisinger, E.C.

    2006-01-01

    Aim: somatostatin receptor scintigraphy images various neoplastic, granulomatous, and auto-immun diseases. Cat-scratch disease in an infectious granulomatous disease usually affecting the lymphnodes. It is not known whether cat-scratch disease provides positive somatostatin receptor scintigrams. Patients, methods: twelve patients with lymphadenitis and suspected cat-scratch disease were investigated by immunofluorescence antibody testing and somatostatin receptor scintigraphy. Suppurated lymphnodes were extracted or drained and Bartonella henselae specific PCR was then performed. Results: eleven of 12 patients showed IgG antibodies against B. henselea. SRS showed positive scintigraphic results in 6 of 11 patients with CSD. B. henselae DNA was detected in tissue of lymphnodes from 4 of 5 patients with lymphnode extraction or lymphnode drainage. SRS demonstrated positive scintigrams in all patients with a positive PCR. In one patient with suspected CSD SRS was negative as well as antibody testing. Conclusion: somatostatin receptor scintigraphy correlated with positive Bartonella henselae specific PCR tests and positive Bartonella henselae specific antibody tests in patients with CSD. (orig.)

  8. Somatostatin receptor scintigraphy in patients with cat-scratch disease

    Energy Technology Data Exchange (ETDEWEB)

    Krause, R.; Schnedl, W.J.; Hoier, S. [Div. of Infectious Diseases, Dept. of Internal Medicine, Univ. Graz (Austria); Piswanger-Soelkner, C.; Lipp, R.W. [Div. of Nuclear Medicine, Dept. of Internal Medicine, Univ. Graz (Austria); Daxboeck, F. [Clinical Inst. for Hygiene and Medical Microbiology, Div. of Hospital Hygiene, Univ. of Vienna (Austria); Reisinger, E.C. [Div. of Infectious Diseases and Tropical Medicine, Dept. of Internal Medicine, Univ. Rostock (Germany)

    2006-07-01

    Aim: somatostatin receptor scintigraphy images various neoplastic, granulomatous, and auto-immun diseases. Cat-scratch disease in an infectious granulomatous disease usually affecting the lymphnodes. It is not known whether cat-scratch disease provides positive somatostatin receptor scintigrams. Patients, methods: twelve patients with lymphadenitis and suspected cat-scratch disease were investigated by immunofluorescence antibody testing and somatostatin receptor scintigraphy. Suppurated lymphnodes were extracted or drained and Bartonella henselae specific PCR was then performed. Results: eleven of 12 patients showed IgG antibodies against B. henselea. SRS showed positive scintigraphic results in 6 of 11 patients with CSD. B. henselae DNA was detected in tissue of lymphnodes from 4 of 5 patients with lymphnode extraction or lymphnode drainage. SRS demonstrated positive scintigrams in all patients with a positive PCR. In one patient with suspected CSD SRS was negative as well as antibody testing. Conclusion: somatostatin receptor scintigraphy correlated with positive Bartonella henselae specific PCR tests and positive Bartonella henselae specific antibody tests in patients with CSD. (orig.)

  9. Kidney protection during peptide receptor radionuclide therapy with somatostatin analogues

    Energy Technology Data Exchange (ETDEWEB)

    Rolleman, Edgar J.; Melis, Marleen; Valkema, Roelf; Krenning, Eric P.; Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, V 220, Rotterdam (Netherlands); Boerman, Otto C. [Radboud University Hospital, Department of Nuclear Medicine, Nijmegen (Netherlands)

    2010-05-15

    This review focuses on the present status of kidney protection during peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues. This treatment modality for somatostatin receptor-positive tumours is limited by renal reabsorption and retention of radiolabelled peptides resulting in dose-limiting high kidney radiation doses. Radiation nephropathy has been described in several patients. Studies on the mechanism and localization demonstrate that renal uptake of radiolabelled somatostatin analogues largely depends on the megalin/cubulin system in the proximal tubule cells. Thus methods are needed that interfere with this reabsorption pathway to achieve kidney protection. Such methods include coadministration of basic amino acids, the bovine gelatin-containing solution Gelofusine or albumin fragments. Amino acids are already commonly used in the clinical setting during PRRT. Other compounds that interfere with renal reabsorption capacity (maleic acid and colchicine) are not suitable for clinical use because of potential toxicity. The safe limit for the renal radiation dose during PRRT is not exactly known. Dosimetry studies applying the principle of the biological equivalent dose (correcting for the effect of dose fractionation) suggest that a dose of about 37 Gy is the threshold for development of kidney toxicity. This threshold is lower when risk factors for development of renal damage exist: age over 60 years, hypertension, diabetes mellitus and previous chemotherapy. A still experimental pathway for kidney protection is mitigation of radiation effects, possibly achievable by cotreatment with amifostine (Ethylol), a radiation protector, or with blockers of the renin-angiotensin-aldosterone system. Future perspectives on improving kidney protection during PRRT include combinations of agents to reduce renal retention of radiolabelled peptides, eventually together with mitigating medicines. Moreover, new somatostatin analogues with lower

  10. Kidney protection during peptide receptor radionuclide therapy with somatostatin analogues

    International Nuclear Information System (INIS)

    Rolleman, Edgar J.; Melis, Marleen; Valkema, Roelf; Krenning, Eric P.; Jong, Marion de; Boerman, Otto C.

    2010-01-01

    This review focuses on the present status of kidney protection during peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues. This treatment modality for somatostatin receptor-positive tumours is limited by renal reabsorption and retention of radiolabelled peptides resulting in dose-limiting high kidney radiation doses. Radiation nephropathy has been described in several patients. Studies on the mechanism and localization demonstrate that renal uptake of radiolabelled somatostatin analogues largely depends on the megalin/cubulin system in the proximal tubule cells. Thus methods are needed that interfere with this reabsorption pathway to achieve kidney protection. Such methods include coadministration of basic amino acids, the bovine gelatin-containing solution Gelofusine or albumin fragments. Amino acids are already commonly used in the clinical setting during PRRT. Other compounds that interfere with renal reabsorption capacity (maleic acid and colchicine) are not suitable for clinical use because of potential toxicity. The safe limit for the renal radiation dose during PRRT is not exactly known. Dosimetry studies applying the principle of the biological equivalent dose (correcting for the effect of dose fractionation) suggest that a dose of about 37 Gy is the threshold for development of kidney toxicity. This threshold is lower when risk factors for development of renal damage exist: age over 60 years, hypertension, diabetes mellitus and previous chemotherapy. A still experimental pathway for kidney protection is mitigation of radiation effects, possibly achievable by cotreatment with amifostine (Ethylol), a radiation protector, or with blockers of the renin-angiotensin-aldosterone system. Future perspectives on improving kidney protection during PRRT include combinations of agents to reduce renal retention of radiolabelled peptides, eventually together with mitigating medicines. Moreover, new somatostatin analogues with lower

  11. Immunohistochemical detection of somatostatin receptor subtypes sst1 and sst2A in human somatostatin receptor positive tumors

    NARCIS (Netherlands)

    L.J. Hofland (Leo); Q. Liu; P.M. van Koetsveld (Peter); J. Zuijderwijk; F. van der Ham (Frieda); R.R. de Krijger (Ronald); A. Schonbrunn; S.W.J. Lamberts (Steven)

    1999-01-01

    textabstractAlthough in situ hybridization has been used to examine the distribution of messenger RNA for somatostatin receptor subtypes (sst) in human tumors, the cellular localization of sst1 and sst2A receptors has not been reported. In this study, we describe the

  12. Truncated somatostatin receptor 5 may modulate therapy response to somatostatin analogues--Observations in two patients with acromegaly and severe headache

    DEFF Research Database (Denmark)

    Marina, Djordje; Burman, Pia; Klose, Marianne

    2015-01-01

    BACKGROUND: Somatotropinomas have unique "fingerprints" of somatostatin receptor (sst) expression, which are targets in treatment of acromegaly with somatostatin analogues (SSAs). However, a significant expression of sst is not always related to the biochemical response to SSAs. Headache is a com...

  13. Hilar somatostatin interneuron loss reduces dentate gyrus inhibition in a mouse model of temporal lobe epilepsy.

    Science.gov (United States)

    Hofmann, Gabrielle; Balgooyen, Laura; Mattis, Joanna; Deisseroth, Karl; Buckmaster, Paul S

    2016-06-01

    In patients with temporal lobe epilepsy, seizures usually start in the hippocampus, and dentate granule cells are hyperexcitable. Somatostatin interneurons are a major subpopulation of inhibitory neurons in the dentate gyrus, and many are lost in patients and animal models. However, surviving somatostatin interneurons sprout axon collaterals and form new synapses, so the net effect on granule cell inhibition remains unclear. The present study uses optogenetics to activate hilar somatostatin interneurons and measure the inhibitory effect on dentate gyrus perforant path-evoked local field potential responses in a mouse model of temporal lobe epilepsy. In controls, light activation of hilar somatostatin interneurons inhibited evoked responses up to 40%. Epileptic pilocarpine-treated mice exhibited loss of hilar somatostatin interneurons and less light-induced inhibition of evoked responses. These findings suggest that severe epilepsy-related loss of hilar somatostatin interneurons can overwhelm the surviving interneurons' capacity to compensate by sprouting axon collaterals. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

  14. Reduced Numbers of Somatostatin Receptors in the Cerebral Cortex in Alzheimer's Disease

    Science.gov (United States)

    Flint Beal, M.; Mazurek, Michael F.; Tran, Vinh T.; Chattha, Geetinder; Bird, Edward D.; Martin, Joseph B.

    1985-07-01

    Somatostatin receptor concentrations were measured in patients with Alzheimer's disease and controls. In the frontal cortex (Brodmann areas 6, 9, and 10) and temporal cortex (Brodmann area 21), the concentrations of somatostatin in receptors in the patients were reduced to approximately 50 percent of control values. A 40 percent reduction was seen in the hippocampus, while no significant changes were found in the cingulate cortex, postcentral gyrus, temporal pole, and superior temporal gyrus. Scatchard analysis showed a reduction in receptor number rather than a change in affinity. Somatostatin-like immunoreactivity was significantly reduced in both the frontal and temporal cortex. Somatostatin-like immunoreactivity was linearly related to somatostatin-receptor binding in the cortices of Alzheimer's patients. These findings may reflect degeneration of postsynaptic neurons or cortical afferents in the patients' cerebral cortices. Alternatively, decreased somatostatinlike immunoreactivity in Alzheimer's disease might indicate increased release of somatostatin and down regulation of postsynaptic receptors.

  15. High molecular somatostatin, an interfering factor in radioimmunoassay

    International Nuclear Information System (INIS)

    Diel, F.; Schneider, E.; Baumann, H.

    1977-01-01

    Cyclic Tyr 1 -somatostatin (Tyr 1 -SRIF) is radioiodinated by the lactoperoxidase method. Purification is achieved by Sephadex G-25 adsorption chromatography. Specific anti-SRIF serum (FA1) has been raised in rabbits. A dose response curve is obtained in the range of 5 - 5,000 pg per tube using an antiserum dilution of 1:2,000. There is little cross-reaction with linear somatostatin and none with ocytocin, (lys-, arg-) vasopressin, valinomycin, polymyxin, insulin, glucagon, human growth hormone (hGH), and thyrotropin-releasing hormone (TRH). For recovery tests, extraction procedures are necessary. Thin-layer chromatography (TLC) and polyacrylamide-disc-electrophoresis (Disc-PAGE) are performed to identify the presumed high molecular 125 I-Tyr 1 -SRIF associate. This high molecular associate may represent an interfering factor in the radioimmunoassay for cyclic SRIF. (orig./AJ) [de

  16. “In-house” preparation of 99mTc-EDDA/HYNIC-TOC, a specific targeting agent for somatostatin receptor scintigraphy

    Directory of Open Access Journals (Sweden)

    Sonja Kuzmanovska

    2012-01-01

    Full Text Available The use of radiolabeled peptide ligands as diagnostics and therapeutics in nuclear oncology has increased recently. One of the most frequently used radiopharmaceutical is 99mTc-EDDA/HYNIC-TOC, a somatostatin analog with affinity for certain types of somatostatin receptors, overexpressed in tumors of neuroendocrine origin. The radiopharmaceutical is not readily available; therefore we introduced its “in house” preparation within project activities supported by the International Atomic Energy Agency (IAEA. We optimized the radiolabeling protocol, prepared a small batch of frozen kits, performed ITLC quality control and animal biodistribution during the preclinical evaluation procedures. The co-ligand exchange labeling procedure was carried out at 100°C during 10 min, resulting in radiochemical purity >90%. The biodistribution scintigrams in normal Wistar rats showed rapid blood clearance after 15 min and predominant kidney accumulation after 4 h, in accordance with the data reported by other authors. Storage stability of the formulated small batch frozen kit (-20°C was evaluated within 6 months, with radiolabeling yield ranging between 94,3% and 96,9%. We conclude that frozen kit can be a safe alternative to the freeze-dried for small batch in house production, and after the satisfactory preclinical evaluation, the “in house” prepared 99mTc-EDDA/ HYNIC-TOC can be introduced in clinical practice as specific targeting agent for somatostatin receptor scintigraphy.

  17. Positron emission tomography study on pancreatic somatostatin receptors in normal and diabetic rats with 68Ga-DOTA-octreotide: a potential PET tracer for beta cell mass measurement.

    Science.gov (United States)

    Sako, Takeo; Hasegawa, Koki; Nishimura, Mie; Kanayama, Yousuke; Wada, Yasuhiro; Hayashinaka, Emi; Cui, Yilong; Kataoka, Yosky; Senda, Michio; Watanabe, Yasuyoshi

    2013-12-06

    Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, and the loss or dysfunction of pancreatic beta cells has been reported before the appearance of clinical symptoms and hyperglycemia. To evaluate beta cell mass (BCM) for improving the detection and treatment of DM at earlier stages, we focused on somatostatin receptors that are highly expressed in the pancreatic beta cells, and developed a positron emission tomography (PET) probe derived from octreotide, a metabolically stable somatostatin analog. Octreotide was conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), a chelating agent, and labeled with (68)Gallium ((68)Ga). After intravenous injection of (68)Ga-DOTA-octreotide, a 90-min emission scan of the abdomen was performed in normal and DM model rats. The PET studies showed that (68)Ga-DOTA-octreotide radioactivity was highly accumulated in the pancreas of normal rats and that the pancreatic accumulation was significantly reduced in the rats administered with an excess amount of unlabeled octreotide or after treatment with streptozotocin, which was used for the chemical induction of DM in rats. These results were in good agreement with the ex vivo biodistribution data. These results indicated that the pancreatic accumulation of (68)Ga-DOTA-octreotide represented specific binding to the somatostatin receptors and reflected BCM. Therefore, PET imaging with (68)Ga-DOTA-octreotide could be a potential tool for evaluating BCM. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Somatostatin receptor subtype expression in human thyroid tumours.

    Science.gov (United States)

    Klagge, A; Krause, K; Schierle, K; Steinert, F; Dralle, H; Fuhrer, D

    2010-04-01

    Somatostatin receptors (SSTR) are expressed in various endocrine tumours. The expression of SSTR at the tumour cell surface confers the possibility for diagnostic imaging and therapy of tumours using radiolabeled somatostatin analogues. The majority of currently available somatostatin analogues show a higher binding affinity for the SSTR2 subtype. To date, the precise expression pattern of the SSTR subtypes 1-5 in thyroid epithelial tumours remains to be determined. We investigated the mRNA expression of SSTR1-5 in benign and malignant epithelial thyroid tumours [20 cold thyroid nodules (CTNs), 20 toxic thyroid nodules (TTNs), 20 papillary, 20 follicular, and 5 anaplastic carcinomas (PTCs, FTCs, ATCs, respectively)] and compared them to normal surrounding thyroid tissues. Four out of five SSTR subtypes were detected in malignant thyroid tumours, benign neoplasia, and normal surrounding tissue with a predominant expression of SSTR2 and SSTR5, and a weak expression of SSTR1 and SSTR3. Weak SSTR4 mRNA expression was detected in some PTCs. Compared to normal thyroid tissue, SSTR2 was significantly upregulated in PTC and ATC. In addition significant upregulation of SSTR3 was found in PTC. SSTR5 mRNA expression was increased in PTC and FTC and significantly decreased in CTN and TTN compared to normal thyroid tissue. SSTR2 is the predominant subtype in thyroid epithelial tumours with a high expression pattern, in particular, in PTC . Perspectively, the expression of distinct SSTR in thyroid epithelial tumours might represent a promising avenue for diagnostics and therapy of advanced thyroid cancer with somatostatin analogues. Georg Thieme Verlag KG Stuttgart New York.

  19. Somatostatin-receptor imaging in the localization of endocrine tumors

    International Nuclear Information System (INIS)

    Lamberts, S.W.; Bakker, W.H.; Reubi, J.C.; Krenning, E.P.

    1990-01-01

    A number of different tumors have receptors for somatostatin. We evaluated the efficacy of scanning with 123 I-labeled Tyr3-octreotide, a somatostatin analogue, for tumor localization in 42 patients with carcinoid tumors, pancreatic endocrine tumors, or paragangliomas. We then evaluated the response to octreotide therapy in some of these patients. Primary tumors or metastases, often previously unrecognized, were visualized in 12 of 13 patients with carcinoid tumors and in 7 of 9 patients with pancreatic endocrine tumors. The endocrine symptoms of these patients responded well to therapy with octreotide. Among 20 patients with paragangliomas, 8 of whom had more than one tumor, 10 temporal (tympanic or jugular), 9 carotid, and 10 vagal tumors could be visualized. One small tympanic tumor and one small carotid tumor were not seen on the scan. The 123 I-labeled Tyr3-octreotide scanning technique is a rapid and safe procedure for the visualization of some tumors with somatostatin receptors. A positive scan may predict the ability of octreotide therapy to control symptoms of hormonal hypersecretion

  20. BA321, a novel carborane analog that binds to androgen and estrogen receptors, acts as a new selective androgen receptor modulator of bone in male mice

    International Nuclear Information System (INIS)

    Watanabe, Kenta; Hirata, Michiko; Tominari, Tsukasa; Matsumoto, Chiho; Endo, Yasuyuki; Murphy, Gillian; Nagase, Hideaki

    2016-01-01

    Carboranes are a class of carbon-containing polyhedral boron cluster compounds with globular geometry and hydrophobic surface that interact with hormone receptors such as estrogen receptor (ER) and androgen receptor (AR). We have synthesized BA321, a novel carborane compound, which binds to AR. We found here that it also binds to ERs, ERα and ERβ. In orchidectomized (ORX) mice, femoral bone mass was markedly reduced due to androgen deficiency and BA321 restored bone loss in the male, whilst the decreased weight of seminal vesicle in ORX mice was not recovered by administration of BA321. In female mice, BA321 acts as a pure estrogen agonist, and restored both the loss of bone mass and uterine atrophy due to estrogen deficiency in ovariectomized (OVX) mice. In bone tissues, the trabecular bone loss occurred in both ORX and OVX mice, and BA321 completely restored the trabecular bone loss in both sexes. Cortical bone loss occurred in ORX mice but not in OVX mice, and BA321 clearly restored cortical bone loss due to androgen deficiency in ORX mice. Therefore, BA321 is a novel selective androgen receptor modulator (SARM) that may offer a new therapy option for osteoporosis in the male. - Highlights: • A novel carborane compound BA321 binds to both AR and ERs, ERα and ERβ. • BA321 restores bone loss in orchidectomized mice without effects on sex organ. • BA321 acts as an estrogen agonist in bone and uterus in ovariectomized mice. • BA321 may be a new SARM to prevent the loss of musculoskeletal mass in elder men.

  1. BA321, a novel carborane analog that binds to androgen and estrogen receptors, acts as a new selective androgen receptor modulator of bone in male mice

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Kenta [Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588 (Japan); Cooperative Major in Advanced Health Science, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588 (Japan); Hirata, Michiko [Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588 (Japan); Tominari, Tsukasa [Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588 (Japan); Institute of Global Innovation Research, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588 (Japan); Matsumoto, Chiho [Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588 (Japan); Endo, Yasuyuki [Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1, Komatsushima, Aoba-ku, Sendai, 981-8558 (Japan); Murphy, Gillian [Department of Oncology, University of Cambridge, Cancer Research UK, Cambridge Institute, Li Ka Shing Centre, Cambridge, CB2 0RE (United Kingdom); Nagase, Hideaki [Institute of Global Innovation Research, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588 (Japan); Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, OX3 7FY (United Kingdom); and others

    2016-09-09

    Carboranes are a class of carbon-containing polyhedral boron cluster compounds with globular geometry and hydrophobic surface that interact with hormone receptors such as estrogen receptor (ER) and androgen receptor (AR). We have synthesized BA321, a novel carborane compound, which binds to AR. We found here that it also binds to ERs, ERα and ERβ. In orchidectomized (ORX) mice, femoral bone mass was markedly reduced due to androgen deficiency and BA321 restored bone loss in the male, whilst the decreased weight of seminal vesicle in ORX mice was not recovered by administration of BA321. In female mice, BA321 acts as a pure estrogen agonist, and restored both the loss of bone mass and uterine atrophy due to estrogen deficiency in ovariectomized (OVX) mice. In bone tissues, the trabecular bone loss occurred in both ORX and OVX mice, and BA321 completely restored the trabecular bone loss in both sexes. Cortical bone loss occurred in ORX mice but not in OVX mice, and BA321 clearly restored cortical bone loss due to androgen deficiency in ORX mice. Therefore, BA321 is a novel selective androgen receptor modulator (SARM) that may offer a new therapy option for osteoporosis in the male. - Highlights: • A novel carborane compound BA321 binds to both AR and ERs, ERα and ERβ. • BA321 restores bone loss in orchidectomized mice without effects on sex organ. • BA321 acts as an estrogen agonist in bone and uterus in ovariectomized mice. • BA321 may be a new SARM to prevent the loss of musculoskeletal mass in elder men.

  2. Effect of Peptide Receptor Radionuclide Therapy on Somatostatin Receptor Status and Glucose Metabolism in Neuroendocrine Tumors: Intraindividual Comparison of Ga-68 DOTANOC PET/CT and F-18 FDG PET/CT

    Science.gov (United States)

    Oh, Sowon; Prasad, Vikas; Lee, Dong Soo; Baum, R. P.

    2011-01-01

    The heterogeneous nature of the neuroendocrine tumors (NET) makes it challenging to find one uniformly applicable management protocol which is especially true for diagnosis. The discovery of the overexpression of somatostatin receptors (SMS-R) on neuroendocrine tumor cells lead to the generalized and rapid acceptance of radiolabeled somatostatin receptor analogs for staging and restaging of NET as well as for Peptide Receptor Radionuclide Therapy (PRRNT) using Y-90 and Lu-177 DOTATATE/DOTATOC. In this present work we tried to look in to the effect of PRRNT on the glucose metabolism assessed by F-18 FDG PET/CT and SMS-R density assessed by Ga-68 DOTANOC PET/CT. We observed a complex relationship between the somatostatin receptor expression and glucose metabolism with only 56% (77/138) of the lesions showing match, while the others show mismatch between the receptor status and metabolism. The match between receptor expression and glucose metabolism increases with the grade of NET. In grade 3 NET, there is a concurrence between the changes in glucose metabolism and somatostatin receptor expression. PRRNT was found to be more effective in lesions with higher receptor expression. PMID:22121482

  3. Somatostatin ontogenesis in the gastrointestinal and pancreatic tract: study in normal rats and during a induced diabetes in neonates rats

    International Nuclear Information System (INIS)

    Cunha, M.C.

    1980-01-01

    The ontogenic studies of somatostatin of pancreas, ileum and duodenum of Wistar rats and the rats with induced diabetes were done. The radioimmunologic method to dose the somatostatin was used. (L.M.J.)

  4. Somatostatin receptor scintigraphy using (99m)Tc-EDDA/HYNIC-TOC in patients with medullary thyroid carcinoma

    NARCIS (Netherlands)

    Czepczynski, Rafal; Parisella, Maria Gemma; Kosowicz, Jerzy; Mikolajczak, Renata; Ziemnicka, Katarzyna; Gryczynska, Maria; Sowinski, Jerzy; Signore, Alberto

    2007-01-01

    Purpose Several new somatostatin analogues have been developed for the diagnosis and therapy of different tumours. Since somatostatin receptors are often over-expressed in medullary thyroid carcinoma (MTC), the aim of our study was to evaluate the utility of scintigraphy with the somatostatin

  5. GH and IGF-I induction by passive immunization of rainbow trout Oncorhynchus mykiss Walbaum using a somatostatin 14 antibody

    Science.gov (United States)

    Inhibition of the growth axis by somatostatin was studied in juvenile rainbow trout using passive immunization with a previously isolated somatostatin antibody (antiSS-14). Upon subcutaneously injection of laying hens (Gallus domesticus) with conjugated somatostatin-14 (SS-14), the antiSS-14 was iso...

  6. Coupling of guanine nucleotide inhibitory protein to somatostatin receptors on pancreatic acinar membranes

    International Nuclear Information System (INIS)

    Sakamoto, C.; Matozaki, T.; Nagao, M.; Baba, S.

    1987-01-01

    Guanine nucleotides and pertussis toxin were used to investigate whether somatostatin receptors interact with the guanine nucleotide inhibitory protein (NI) on pancreatic acinar membranes in the rat. Guanine nucleotides reduced 125 I-[Tyr 1 ]somatostatin binding to acinar membranes up to 80%, with rank order of potency being 5'-guanylyl imidodiphosphate [Gpp(NH)p]>GTP>TDP>GMP. Scatchard analysis revealed that the decrease in somatostatin binding caused by Gpp(NH)p was due to the decrease in the maximum binding capacity without a significant change in the binding affinity. The inhibitory effect of Gpp(NH)p was partially abolished in the absence of Mg 2+ . When pancreatic acini were treated with 1 μg/ml pertussis toxin for 4 h, subsequent 125 I-[Tyr 1 ]somatostatin binding to acinar membranes was reduced. Pertussis toxin treatment also abolished the inhibitory effect of somatostatin on vasoactive intestinal peptide-stimulated increase in cellular content of adenosine 3',5'-cyclic monophosphate (cAMP) in the acini. The present results suggest that 1) somatostatin probably functions in the pancreas to regulate adenylate cyclase enzyme system via Ni, 2) the extent of modification of Ni is correlated with the ability of somatostatin to inhibit cAMP accumulation in acini, and 3) guanine nucleotides also inhibit somatostatin binding to its receptor

  7. Cholecystokinin inhibits gastrin secretion independently of paracrine somatostatin secretion in the pig

    DEFF Research Database (Denmark)

    Schmidt, P T; Hansen, L; Hilsted, L

    2004-01-01

    BACKGROUND: Cholecystokinin inhibits the secretion of gastrin from antral G cells, an effect that is speculated to be mediated by D cells secreting somatostatin. The aim of the study was to test directly whether cholecystokinin inhibition of antral gastrin secretion is mediated by somatostatin....... METHODS: The effects of CCK on gastrin and somatostatin secretion were studied in isolated vascularly perfused preparations of pig antrum before and after immunoneutralization brought about by infusion of large amounts of a high affinity monoclonal antibody against somatostatin. RESULTS: CCK infusion...... at 10(-9) M and 10(-8) M decreased gastrin output to 70.5% +/- 7.6% (n = 8) and 76.3% +/- 3.6% (n = 7) of basal output, respectively. CCK at 10(-10) M had no effect (n = 6). Somatostatin secretion was dose-dependently increased by CCK infusion and increased to 268 +/- 38.2% (n = 7) of basal secretion...

  8. Localisation and mechanism of renal retention of radiolabelled somatostatin analogues

    Energy Technology Data Exchange (ETDEWEB)

    Melis, Marleen; Krenning, Eric P.; Bernard, Bert F.; Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Barone, Raffaella [UCL, Centre of Nuclear Medicine and Laboratory of PET, Brussels (Belgium); Visser, Theo J. [Erasmus MC, Department of Internal Medicine, Rotterdam (Netherlands)

    2005-10-01

    Radiolabelled somatostatin analogues, such as octreotide and octreotate, are used for tumour scintigraphy and radionuclide therapy. The kidney is the most important critical organ during such therapy owing to the reabsorption and retention of radiolabelled peptides. The aim of this study was to investigate in a rat model both the localisation and the mechanism of renal uptake after intravenous injection of radiolabelled somatostatin analogues. The multi-ligand megalin/cubilin receptor complex, responsible for reabsorption of many peptides and proteins in the kidney, is an interesting candidate for renal endocytosis of these peptide analogues. For localisation studies, ex vivo autoradiography and micro-autoradiography of rat kidneys were performed 1-24 h after injection of radiolabelled somatostatin analogues and compared with the renal anti-megalin immunohistochemical staining pattern. To confirm a role of megalin in the mechanism of renal retention of [{sup 111}In-DTPA]octreotide, the effects of three inhibitory substances were explored in rats. Renal ex vivo autoradiography showed high cortical radioactivity and lower radioactivity in the outer medulla. The distribution of cortical radioactivity was inhomogeneous. Micro-autoradiography indicated that radioactivity was only retained in the proximal tubules. The anti-megalin immunohistochemical staining pattern showed a strong similarity with the renal [{sup 111}In-DTPA]octreotide ex vivo autoradiograms. Biodistribution studies showed that co-injection of positively charged d-lysine reduced renal uptake to 60% of control. Sodium maleate reduced renal [{sup 111}In-DTPA]octreotide uptake to 15% of control. Finally, cisplatin pre-treatment of rats reduced kidney uptake to 70% of control. Renal retention of [{sup 111}In-DTPA]octreotide is confined to proximal tubules in the rat kidney, in which megalin-mediated endocytosis may play an important part. (orig.)

  9. Cell-to-cell communication and cellular environment alter the somatostatin status of delta cells

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, Catriona, E-mail: catriona.kelly@qub.ac.uk [SAAD Centre for Pharmacy and Diabetes, School of Biomedical Sciences, University of Ulster, Coleraine (United Kingdom); Flatt, Peter R.; McClenaghan, Neville H. [SAAD Centre for Pharmacy and Diabetes, School of Biomedical Sciences, University of Ulster, Coleraine (United Kingdom)

    2010-08-20

    Research highlights: {yields} TGP52 cells display enhanced functionality in pseudoislet form. {yields} Somatostatin content was reduced, but secretion increased in high glucose conditions. {yields} Cellular interactions and environment alter the somatostatin status of TGP52 cells. -- Abstract: Introduction: Somatostatin, released from pancreatic delta cells, is a potent paracrine inhibitor of insulin and glucagon secretion. Islet cellular interactions and glucose homeostasis are essential to maintain normal patterns of insulin secretion. However, the importance of cell-to-cell communication and cellular environment in the regulation of somatostatin release remains unclear. Methods: This study employed the somatostatin-secreting TGP52 cell line maintained in DMEM:F12 (17.5 mM glucose) or DMEM (25 mM glucose) culture media. The effect of pseudoislet formation and culture medium on somatostatin content and release in response to a variety of stimuli was measured by somatostatin EIA. In addition, the effect of pseudoislet formation on cellular viability (MTT and LDH assays) and proliferation (BrdU ELISA) was determined. Results: TGP52 cells readily formed pseudoislets and showed enhanced functionality in three-dimensional form with increased E-cadherin expression irrespective of the culture environment used. However, culture in DMEM decreased cellular somatostatin content (P < 0.01) and increased somatostatin secretion in response to a variety of stimuli including arginine, calcium and PMA (P < 0.001) when compared with cells grown in DMEM:F12. Configuration of TGP52 cells as pseudoislets reduced the proliferative rate and increased cellular cytotoxicity irrespective of culture medium used. Conclusions: Somatostatin secretion is greatly facilitated by cell-to-cell interactions and E-cadherin expression. Cellular environment and extracellular glucose also significantly influence the function of delta cells.

  10. Cell-to-cell communication and cellular environment alter the somatostatin status of delta cells

    International Nuclear Information System (INIS)

    Kelly, Catriona; Flatt, Peter R.; McClenaghan, Neville H.

    2010-01-01

    Research highlights: → TGP52 cells display enhanced functionality in pseudoislet form. → Somatostatin content was reduced, but secretion increased in high glucose conditions. → Cellular interactions and environment alter the somatostatin status of TGP52 cells. -- Abstract: Introduction: Somatostatin, released from pancreatic delta cells, is a potent paracrine inhibitor of insulin and glucagon secretion. Islet cellular interactions and glucose homeostasis are essential to maintain normal patterns of insulin secretion. However, the importance of cell-to-cell communication and cellular environment in the regulation of somatostatin release remains unclear. Methods: This study employed the somatostatin-secreting TGP52 cell line maintained in DMEM:F12 (17.5 mM glucose) or DMEM (25 mM glucose) culture media. The effect of pseudoislet formation and culture medium on somatostatin content and release in response to a variety of stimuli was measured by somatostatin EIA. In addition, the effect of pseudoislet formation on cellular viability (MTT and LDH assays) and proliferation (BrdU ELISA) was determined. Results: TGP52 cells readily formed pseudoislets and showed enhanced functionality in three-dimensional form with increased E-cadherin expression irrespective of the culture environment used. However, culture in DMEM decreased cellular somatostatin content (P < 0.01) and increased somatostatin secretion in response to a variety of stimuli including arginine, calcium and PMA (P < 0.001) when compared with cells grown in DMEM:F12. Configuration of TGP52 cells as pseudoislets reduced the proliferative rate and increased cellular cytotoxicity irrespective of culture medium used. Conclusions: Somatostatin secretion is greatly facilitated by cell-to-cell interactions and E-cadherin expression. Cellular environment and extracellular glucose also significantly influence the function of delta cells.

  11. Science Teachers' Analogical Reasoning

    Science.gov (United States)

    Mozzer, Nilmara Braga; Justi, Rosária

    2013-08-01

    Analogies can play a relevant role in students' learning. However, for the effective use of analogies, teachers should not only have a well-prepared repertoire of validated analogies, which could serve as bridges between the students' prior knowledge and the scientific knowledge they desire them to understand, but also know how to introduce analogies in their lessons. Both aspects have been discussed in the literature in the last few decades. However, almost nothing is known about how teachers draw their own analogies for instructional purposes or, in other words, about how they reason analogically when planning and conducting teaching. This is the focus of this paper. Six secondary teachers were individually interviewed; the aim was to characterize how they perform each of the analogical reasoning subprocesses, as well as to identify their views on analogies and their use in science teaching. The results were analyzed by considering elements of both theories about analogical reasoning: the structural mapping proposed by Gentner and the analogical mechanism described by Vosniadou. A comprehensive discussion of our results makes it evident that teachers' content knowledge on scientific topics and on analogies as well as their pedagogical content knowledge on the use of analogies influence all their analogical reasoning subprocesses. Our results also point to the need for improving teachers' knowledge about analogies and their ability to perform analogical reasoning.

  12. Somatostatin Negatively Regulates Parasite Burden and Granulomatous Responses in Cysticercosis

    Directory of Open Access Journals (Sweden)

    Mitra Khumbatta

    2014-01-01

    Full Text Available Cysticercosis is an infection of tissues with the larval cysts of the cestode, Taenia  solium. While live parasites elicit little or no inflammation, dying parasites initiate a granulomatous reaction presenting as painful muscle nodules or seizures when cysts are located in the brain. We previously showed in the T. crassiceps murine model of cysticercosis that substance P (SP, a neuropeptide, was detected in early granulomas and was responsible for promoting granuloma formation, while somatostatin (SOM, another neuropeptide and immunomodulatory hormone, was detected in late granulomas; SOM’s contribution to granuloma formation was not examined. In the current studies, we used somatostatin knockout (SOM−/− mice to examine the hypothesis that SOM downmodulates granulomatous inflammation in cysticercosis, thereby promoting parasite growth. Our results demonstrated that parasite burden was reduced 5.9-fold in SOM−/− mice compared to WT mice (P<0.05. This reduction in parasite burden in SOM−/− mice was accompanied by a 95% increase in size of their granulomas (P<0.05, which contained a 1.5-fold increase in levels of IFN-γ and a 26-fold decrease in levels of IL-1β (P<0.05 for both compared to granulomas from WT mice. Thus, SOM regulates both parasite burden and granulomatous inflammation perhaps through modulating granuloma production of IFN-γ and IL-1β.

  13. Active postoperative acromegaly: sustained remission after discontinuation of somatostatin analogues

    Directory of Open Access Journals (Sweden)

    Cristina Alvarez-Escola

    2016-11-01

    Full Text Available In patients with active acromegaly after pituitary surgery, somatostatin analogues are effective in controlling the disease and can even be curative in some cases. After treatment discontinuation, the likelihood of disease recurrence is high. However, a small subset of patients remains symptom-free after discontinuation, with normalized growth hormone (GH and insulin-like growth factor (IGF1 levels. The characteristics of patients most likely to achieve sustained remission after treatment discontinuation are not well understood, although limited evidence suggests that sustained remission is more likely in patients with lower GH and IGF1 levels before treatment withdrawal, in those who respond well to low-dose treatment, in those without evidence of adenoma on an MRI scan and/or in patients who receive long-term treatment. In this report, we describe the case of a 56-year-old female patient treated with lanreotide Autogel for 11 years. Treatment was successfully discontinued, and the patient is currently disease-free on all relevant parameters (clinical, biochemical and tumour status. The successful outcome in this case adds to the small body of literature suggesting that some well-selected patients who receive long-term treatment with somatostatin analogues may achieve sustained remission.

  14. Intuitive analog circuit design

    CERN Document Server

    Thompson, Marc

    2013-01-01

    Intuitive Analog Circuit Design outlines ways of thinking about analog circuits and systems that let you develop a feel for what a good, working analog circuit design should be. This book reflects author Marc Thompson's 30 years of experience designing analog and power electronics circuits and teaching graduate-level analog circuit design, and is the ideal reference for anyone who needs a straightforward introduction to the subject. In this book, Dr. Thompson describes intuitive and ""back-of-the-envelope"" techniques for designing and analyzing analog circuits, including transistor amplifi

  15. The radioimmunoassay and physiology of somatostatin in the pancreas and gastrointestinal tract.

    Science.gov (United States)

    McIntosh, C; Arnold, R

    1978-05-01

    Radioimmunoassays for somatostain have demonstrated that high concentrations of the polypeptide are present in the pancreas and gastrointestinal tract of a number of species. Although measurement in tissue extracts is relatively unproblematic, detection and characterization of somatostatin-like material in plasma has proved technically difficult. Studies of pancreatic somatostatin release in vitro suggest a possible function in the regulation of islet hormone secretion, but the mode of action remains to be elucidated. Although, at present, no clinical relevance can be attributed to the somatostain radioimmunoassay reports of somatostatin secreting tumors and changes in stomach tissue content in patients with ulcer disease indicate a contributory role in the pathophysiology of certain disease states.

  16. Activation of Brain Somatostatin Signaling Suppresses CRF Receptor-Mediated Stress Response

    Directory of Open Access Journals (Sweden)

    Andreas Stengel

    2017-04-01

    Full Text Available Corticotropin-releasing factor (CRF is the hallmark brain peptide triggering the response to stress and mediates—in addition to the stimulation of the hypothalamus-pituitary-adrenal (HPA axis—other hormonal, behavioral, autonomic and visceral components. Earlier reports indicate that somatostatin-28 injected intracerebroventricularly counteracts the acute stress-induced ACTH and catecholamine release. Mounting evidence now supports that activation of brain somatostatin signaling exerts a broader anti-stress effect by blunting the endocrine, autonomic, behavioral (with a focus on food intake and visceral gastrointestinal motor responses through the involvement of distinct somatostatin receptor subtypes.

  17. Activation of Brain Somatostatin Signaling Suppresses CRF Receptor-Mediated Stress Response.

    Science.gov (United States)

    Stengel, Andreas; Taché, Yvette F

    2017-01-01

    Corticotropin-releasing factor (CRF) is the hallmark brain peptide triggering the response to stress and mediates-in addition to the stimulation of the hypothalamus-pituitary-adrenal (HPA) axis-other hormonal, behavioral, autonomic and visceral components. Earlier reports indicate that somatostatin-28 injected intracerebroventricularly counteracts the acute stress-induced ACTH and catecholamine release. Mounting evidence now supports that activation of brain somatostatin signaling exerts a broader anti-stress effect by blunting the endocrine, autonomic, behavioral (with a focus on food intake) and visceral gastrointestinal motor responses through the involvement of distinct somatostatin receptor subtypes.

  18. Rhetoric and analogies

    OpenAIRE

    Aragonès, Enriqueta; Gilboa, Itzhak; Postlewaite, Andrew; Schmeidler, David; Universitat Autònoma de Barcelona. Unitat de Fonaments de l'Anàlisi Econòmica; Universitat Autònoma de Barcelona. Institut d'Anàlisi Econòmica

    2013-01-01

    The art of rhetoric may be defined as changing other people's minds (opinions, beliefs) without providing them new information. One tech- nique heavily used by rhetoric employs analogies. Using analogies, one may draw the listener's attention to similarities between cases and to re-organize existing information in a way that highlights certain reg- ularities. In this paper we offer two models of analogies, discuss their theoretical equivalence, and show that finding good analogies is a com- p...

  19. Correlation of Somatostatin Receptor-2 Expression with Gallium-68-DOTA-TATE Uptake in Neuroblastoma Xenograft Models.

    Science.gov (United States)

    Zhang, Libo; Vines, Douglass C; Scollard, Deborah A; McKee, Trevor; Komal, Teesha; Ganguly, Milan; Do, Trevor; Wu, Bing; Alexander, Natasha; Vali, Reza; Shammas, Amer; Besanger, Travis; Baruchel, Sylvain

    2017-01-01

    Peptide-receptor imaging and therapy with radiolabeled somatostatin analogs such as 68 Ga-DOTA-TATE and 177 Lu-DOTA-TATE have become an effective treatment option for SSTR-positive neuroendocrine tumors. The purpose of this study was to evaluate the correlation of somatostatin receptor-2 (SSTR2) expression with 68 Ga-DOTA-TATE uptake and 177 Lu-DOTA-TATE therapy in neuroblastoma (NB) xenograft models. We demonstrated variable SSTR2 expression profiles in eight NB cell lines. From micro-PET imaging and autoradiography, a higher uptake of 68 Ga-DOTA-TATE was observed in SSTR2 high-expressing NB xenografts (CHLA-15) compared to SSTR2 low-expressing NB xenografts (SK-N-BE(2)). Combined autoradiography-immunohistochemistry revealed histological colocalization of SSTR2 and 68 Ga-DOTA-TATE uptake in CHLA-15 tumors. With a low dose of 177 Lu-DOTA-TATE (20 MBq/animal), tumor growth inhibition was achieved in the CHLA-15 high SSTR2 expressing xenograft model. Although, in vitro , NB cells showed variable expression levels of norepinephrine transporter (NET), a molecular target for 131 I-MIBG therapy, low 123 I-MIBG uptake was observed in all selected NB xenografts. In conclusion, SSTR2 expression levels are associated with 68 Ga-DOTA-TATE uptake and antitumor efficacy of 177 Lu-DOTA-TATE. 68 Ga-DOTA-TATE PET is superior to 123 I-MIBG SPECT imaging in detecting NB tumors in our model. Radiolabeled DOTA-TATE can be used as an agent for NB tumor imaging to potentially discriminate tumors eligible for 177 Lu-DOTA-TATE therapy.

  20. Correlation of Somatostatin Receptor-2 Expression with Gallium-68-DOTA-TATE Uptake in Neuroblastoma Xenograft Models

    Directory of Open Access Journals (Sweden)

    Libo Zhang

    2017-01-01

    Full Text Available Peptide-receptor imaging and therapy with radiolabeled somatostatin analogs such as 68Ga-DOTA-TATE and 177Lu-DOTA-TATE have become an effective treatment option for SSTR-positive neuroendocrine tumors. The purpose of this study was to evaluate the correlation of somatostatin receptor-2 (SSTR2 expression with 68Ga-DOTA-TATE uptake and 177Lu-DOTA-TATE therapy in neuroblastoma (NB xenograft models. We demonstrated variable SSTR2 expression profiles in eight NB cell lines. From micro-PET imaging and autoradiography, a higher uptake of 68Ga-DOTA-TATE was observed in SSTR2 high-expressing NB xenografts (CHLA-15 compared to SSTR2 low-expressing NB xenografts (SK-N-BE(2. Combined autoradiography-immunohistochemistry revealed histological colocalization of SSTR2 and 68Ga-DOTA-TATE uptake in CHLA-15 tumors. With a low dose of 177Lu-DOTA-TATE (20 MBq/animal, tumor growth inhibition was achieved in the CHLA-15 high SSTR2 expressing xenograft model. Although, in vitro, NB cells showed variable expression levels of norepinephrine transporter (NET, a molecular target for 131I-MIBG therapy, low 123I-MIBG uptake was observed in all selected NB xenografts. In conclusion, SSTR2 expression levels are associated with 68Ga-DOTA-TATE uptake and antitumor efficacy of 177Lu-DOTA-TATE. 68Ga-DOTA-TATE PET is superior to 123I-MIBG SPECT imaging in detecting NB tumors in our model. Radiolabeled DOTA-TATE can be used as an agent for NB tumor imaging to potentially discriminate tumors eligible for 177Lu-DOTA-TATE therapy.

  1. Analog and hybrid computing

    CERN Document Server

    Hyndman, D E

    2013-01-01

    Analog and Hybrid Computing focuses on the operations of analog and hybrid computers. The book first outlines the history of computing devices that influenced the creation of analog and digital computers. The types of problems to be solved on computers, computing systems, and digital computers are discussed. The text looks at the theory and operation of electronic analog computers, including linear and non-linear computing units and use of analog computers as operational amplifiers. The monograph examines the preparation of problems to be deciphered on computers. Flow diagrams, methods of ampl

  2. Structured Analog CMOS Design

    CERN Document Server

    Stefanovic, Danica

    2008-01-01

    Structured Analog CMOS Design describes a structured analog design approach that makes it possible to simplify complex analog design problems and develop a design strategy that can be used for the design of large number of analog cells. It intentionally avoids treating the analog design as a mathematical problem, developing a design procedure based on the understanding of device physics and approximations that give insight into parameter interdependences. The proposed transistor-level design procedure is based on the EKV modeling approach and relies on the device inversion level as a fundament

  3. Somatostatin receptors in rat hippocampus: localization to intrinsic neurons

    International Nuclear Information System (INIS)

    Palacios, J.M.; Reubi, J.C.; Maurer, R.

    1986-01-01

    The effect of neurotoxic chemical and electrolytical lesions on somatostatin (SS) receptor binding in the septo-hippocampal afferents, pyramidal and granule cells of the rat hippocampus was examined by autoradiography using the stable SS analogue 125 I-204-090 as radioligand. Electrolytical lesions of the septum did not result in modification of SS binding in the hippocampus. In contrast, both granule cell lesion with colchicine and pyramidal or pyramidal and granule cell lesions with increasing kainic acid doses did result in a specific decrease of binding in the dentate gyrus and hippocampus (CA 1 and CA 3 ). These results suggest that SS receptors in the hippocampus are probably associated with elements from intrinsic neurons. (Author)

  4. Somatostatin analogues labelled with 99mTc

    International Nuclear Information System (INIS)

    Obenaus, Esteban R.; Crudo, Jose L.; Edreira, Martin M.; Castiglia, Silvia G.

    1999-01-01

    Biological and radiochemical studies have been carried out on two labelled somatostatin analogues, the peptide RC-150 and the Tyr 3 -Octreotide. Both analogues have been labelled with 99m Tc using the direct and the indirect method and MAG-3 and HYNIC as chelating agents. By the direct method RC-150 was labelled using sodium ascorbate and dithionite as reducing agents. The radiochemical purity was 70%. By the indirect method, in the case of RC-160 with MAG-3 a radiochemical purity higher than 70% was attained while a purity of 100% was reached in the case of Tyr 3 -Octreotide with HYNIC. The biological distribution of HYNIC-Tyr 3 -Octreotide has been studied in rats. (author)

  5. Physiologic basics and clinical experience with somatostatin-receptor-scintigraphy

    International Nuclear Information System (INIS)

    Henze, E.; Eberhardt, J.U.; Bohuslavizki, K.H.

    1994-01-01

    The introduction of radiolabelled octreotide, an analogon to the receptor binding hormone Somatostatin, has markedly increased the ability to detect structures and tumours carrying somatostatin receptors by nuclear medicine imaging with high sensitivity and specificity. It has been shown that in vitro receptor density and in vivo scintigraphic results correlate well in particular in tumours of neuroendocrine origin of the GI tract such as insulinomas, gastrinomas, glucagonomas, carcionoids, but also in paragangliomas, small cell lung cancer and meningiomas. As receptors were also shown to be present on so called activated leucocytes granulomas, lymphomas and autoimmune disease have been imaged with octreotide successfully. The specific tracer (In-111-DTPA-D-PHE-Octreotide, Octreoscan R ) is rapidly cleared from the blood pool by the kidneys and, partially, via the liver providing a high target to background ratio. Physiologic uptake is usually observed in the pituitary and thyroid glands, in spleen and liver. Optimum tracer accumulation for tumour scintigraphy is seen on the 24-h-images with the best target to background ratios. Additional SPECT-imaging is recommended in particular in the abdominal regions. The sensitivity in imaging the above named tumours ranges from 70 up to 100%. In-111 octreotide imaging is of diagnostic impact both for the primary diagnostic evaluation as well as for detecting or excluding secondary manifestations in known tumour sites. Of specific value is the information on relative receptor density in the tumour to be treated as may be obtained by quantitative In-111 octreotide imaging for decision making whether or not to use cold octreotide (Sandostatin R ) as a receptor blocking drug for therapy as well as for treatment follow-up studies. (author)

  6. Somatostatin receptor 2A expression in choroidal neovascularization secondary to age-related macular degeneration

    NARCIS (Netherlands)

    A.C. Lambooij (Antoinette); R.W.A.M. Kuijpers (Robert); E.G. van Lichtenauer-Kaligis; M. Kliffen (Mike); G.S. Baarsma (Seerp); P.M. van Hagen (Martin); C.M. Mooy (Cornelia)

    2000-01-01

    textabstractPURPOSE: The growth of ocular neovascularization is regulated by a balance between stimulating and inhibiting growth factors. Somatostatin affects angiogenesis by inhibiting the growth hormone-insulin-like growth factor axis and also has a direct

  7. Activation of Brain Somatostatin Signaling Suppresses CRF Receptor-Mediated Stress Response

    OpenAIRE

    Andreas Stengel; Yvette F. Taché; Yvette F. Taché

    2017-01-01

    Corticotropin-releasing factor (CRF) is the hallmark brain peptide triggering the response to stress and mediates—in addition to the stimulation of the hypothalamus-pituitary-adrenal (HPA) axis—other hormonal, behavioral, autonomic and visceral components. Earlier reports indicate that somatostatin-28 injected intracerebroventricularly counteracts the acute stress-induced ACTH and catecholamine release. Mounting evidence now supports that activation of brain somatostatin signaling exerts a br...

  8. Depletion of somatostatin-like immunoreactivity in the rat central nervous system by cysteamine

    International Nuclear Information System (INIS)

    Sagar, S.M.; Landry, D.; Millard, W.J.; Badger, T.M.; Arnold, M.A.; Martin, J.B.

    1982-01-01

    Selective neurotoxins have been of value in providing a means for specifically interfering with the actions of endogenous neurotransmitter candidates. Others have shown cysteamine (CSH) to deplete the gastrointestinal tract and hypothalamus of rats of immunoreactive somatostatin, suggesting a toxic action of that compound directed against somatostatin-containing cells. The present study further defines the actions of cysteamine on somatostatin in the central nervous system. (CNS). Cysteamine hydrochloride administered subcutaneously results in a depletion of somatostatin-like immunoreactivity (SLI) in the retina, brain, and cervical spinal cord of rats. The effect is demonstrable at doses of 30 mg/kg of body weight and above, occurs within 2 to 4 hr of a single injection of the drug, and is largely reversible within 1 week. The mean depletion of SLI observed within the CNS varies from 38% in cerebral cortex to 65% in cervical spinal cord 24 hr following administration of CSH, 300 mg/kg of body weight, s.c. By gel permeation chromatography, all molecular weight forms of SLI are affected, with the largest reductions in those forms that co-chromatograph with synthetic somatostatin-14 and somatostatin-28. These results indicate that CSH has a generalized, rapid, and largely reversible effect in depleting SLI from the rat CNS

  9. In vivo somatostatin, vasopressin, and oxytocin synthesis in diabetic rat hypothalamus

    International Nuclear Information System (INIS)

    Fernstrom, J.D.; Fernstrom, M.H.; Kwok, R.P.

    1990-01-01

    The in vivo labeling of somatostatin-14, somatostatin-28, arginine vasopressin, and oxytocin was studied in rat hypothalamus after third ventricular administration of [35S]cysteine to streptozotocin-diabetic and normal rats. Immunoreactive somatostatin levels in hypothalamus were unaffected by diabetes, as was the incorporation of [35S]cysteine into hypothalamic somatostatin-14 and somatostatin-28. In contrast, immunoreactive vasopressin levels in hypothalamus and posterior pituitary (and oxytocin levels in posterior pituitary) were below normal in diabetic rats. Moreover, [35S]cysteine incorporation into hypothalamic vasopressin and oxytocin (probably mainly in the paraventricular nucleus because of its proximity to the third ventricular site of label injection) was significantly above normal. The increments in vasopressin and oxytocin labeling were reversed by insulin administration. In vivo cysteine specific activity and the labeling of acid-precipitable protein did not differ between normal and diabetic animals; effects of diabetes on vasopressin and oxytocin labeling were therefore not caused by simple differences in cysteine specific activity. These results suggest that diabetes (1) does not influence the production of somatostatin peptides in hypothalamus but (2) stimulates the synthesis of vasopressin and oxytocin. For vasopressin at least, the increase in synthesis may be a compensatory response to the known increase in its secretion that occurs in uncontrolled diabetes

  10. Iodination and stability of somatostatin analogues: comparison of iodination techniques. A practical overview.

    Science.gov (United States)

    de Blois, Erik; Chan, Ho Sze; Breeman, Wouter A P

    2012-01-01

    For iodination ((125/127)I) of tyrosine-containing peptides, chloramin-T, Pre-Coated Iodo-Gen(®) tubes and Iodo-Beads(®) (Pierce) are commonly used for in vitro radioligand investigations and there have been reliant vendors hereof for decades. However, commercial availability of these radio-iodinated peptides is decreasing. For continuation of our research in this field we investigated and optimized (radio-)iodination of somatostatin analogues. In literature, radioiodination using here described somatostatin analogues and iodination techniques are described separately. Here we present an overview, including High Performance Liquid Chromatography (HPLC) separation and characterisation by mass spectrometry, to obtain mono- and di-iodinated analogues. Reaction kinetics of (125/127)I iodinated somatostatin analogues were investigated as function of reaction time and concentration of reactants, including somatostatin analogues, iodine and oxidizing agent. To our knowledge, for the here described somatostatin analogues, no (127)I iodination and optimization are described. (Radio-)iodinated somatostatin analogues could be preserved with a >90% radiochemical purity for 1 month after reversed phase HPLC-purification.

  11. Detecting analogies unconsciously

    Directory of Open Access Journals (Sweden)

    Thomas Peter Reber

    2014-01-01

    Full Text Available Analogies may arise from the conscious detection of similarities between a present and a past situation. In this functional magnetic resonance imaging study, we tested whether young volunteers would detect analogies unconsciously between a current supraliminal (visible and a past subliminal (invisible situation. The subliminal encoding of the past situation precludes awareness of analogy detection in the current situation. First, participants encoded subliminal pairs of unrelated words in either one or nine encoding trials. Later, they judged the semantic fit of supraliminally presented new words that either retained a previously encoded semantic relation (‘analog’ or not (‘broken analog’. Words in analogs versus broken analogs were judged closer semantically, which reflects unconscious analogy detection. Hippocampal activity associated with subliminal encoding correlated with the behavioral measure of unconscious analogy detection. Analogs versus broken analogs were processed with reduced prefrontal but enhanced medial temporal activity. We conclude that analogous episodes can be detected even unconsciously drawing on the episodic memory network.

  12. New octreotide derivatives for in vivo targeting of somatostatin receptor-positive tumors for Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET)

    International Nuclear Information System (INIS)

    Maecke, H.R.; Smith-Jones, P.; Maina, T.; Stolz, B.; Albert, R.; Bruns, C.; Reist, H.

    1993-01-01

    Two new modifications of the somatostatin analog octreotide, designed to hold the gallium isotopes 67 Ga and 68 Ga (DFO-SMS) and 99m Tc (PnAO-SMS) have been synthesized and evaluated in vitro and in vivo in tumor bearing rats. DFO-SMS can be labeled with 67 Ga 3+ and 68 Ga 3+ with high specific activity within less than 30 minutes in a ''cold kit'' type formulation. The labeled conjugate is stable under physiologgical conditions. Moreover the binding affinity to somatostatin receptors on rat brain cortex membranes was shown to be retained. In vivo fast tumor localization was demonstrated and the pharmacokinetics proved to be favourable as the main excretion route was via the kidneys. First PET studies with [ 68 Ga]-DFO-SMS showed a rapid accumulation in the tumor and a residence half-life at the tumor site of about 6 hours. PnAO-SMS can be labeled with 99m Tc with high radiochemical purity. In vivo the radiotracer accumulates well in the tumor but due to its high lipohilicity, its main excretion route is via the hepatobiliary system. (orig.)

  13. Analog circuit design

    CERN Document Server

    Dobkin, Bob

    2012-01-01

    Analog circuit and system design today is more essential than ever before. With the growth of digital systems, wireless communications, complex industrial and automotive systems, designers are being challenged to develop sophisticated analog solutions. This comprehensive source book of circuit design solutions aids engineers with elegant and practical design techniques that focus on common analog challenges. The book's in-depth application examples provide insight into circuit design and application solutions that you can apply in today's demanding designs. <

  14. Analog synthetic biology.

    Science.gov (United States)

    Sarpeshkar, R

    2014-03-28

    We analyse the pros and cons of analog versus digital computation in living cells. Our analysis is based on fundamental laws of noise in gene and protein expression, which set limits on the energy, time, space, molecular count and part-count resources needed to compute at a given level of precision. We conclude that analog computation is significantly more efficient in its use of resources than deterministic digital computation even at relatively high levels of precision in the cell. Based on this analysis, we conclude that synthetic biology must use analog, collective analog, probabilistic and hybrid analog-digital computational approaches; otherwise, even relatively simple synthetic computations in cells such as addition will exceed energy and molecular-count budgets. We present schematics for efficiently representing analog DNA-protein computation in cells. Analog electronic flow in subthreshold transistors and analog molecular flux in chemical reactions obey Boltzmann exponential laws of thermodynamics and are described by astoundingly similar logarithmic electrochemical potentials. Therefore, cytomorphic circuits can help to map circuit designs between electronic and biochemical domains. We review recent work that uses positive-feedback linearization circuits to architect wide-dynamic-range logarithmic analog computation in Escherichia coli using three transcription factors, nearly two orders of magnitude more efficient in parts than prior digital implementations.

  15. Positron emission tomography study on pancreatic somatostatin receptors in normal and diabetic rats with {sup 68}Ga-DOTA-octreotide: A potential PET tracer for beta cell mass measurement

    Energy Technology Data Exchange (ETDEWEB)

    Sako, Takeo [Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Division of Molecular Imaging, Institute of Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017 (Japan); Hasegawa, Koki; Nishimura, Mie; Kanayama, Yousuke; Wada, Yasuhiro; Hayashinaka, Emi; Cui, Yilong; Kataoka, Yosky [Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Senda, Michio [Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Division of Molecular Imaging, Institute of Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017 (Japan); Watanabe, Yasuyoshi, E-mail: yywata@riken.jp [Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan)

    2013-12-06

    Highlights: •PET images showed high uptake of {sup 68}Ga-DOTA-octreotide in the normal pancreas. •{sup 68}Ga-DOTA-octreotide specifically binds to somatostatin receptors in the pancreas. •The pancreatic uptake of {sup 68}Ga-DOTA-octreotide was decreased in the diabetic rats. •{sup 68}Ga-DOTA-octreotide could be a candidate PET probe to measure the beta cell mass. -- Abstract: Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, and the loss or dysfunction of pancreatic beta cells has been reported before the appearance of clinical symptoms and hyperglycemia. To evaluate beta cell mass (BCM) for improving the detection and treatment of DM at earlier stages, we focused on somatostatin receptors that are highly expressed in the pancreatic beta cells, and developed a positron emission tomography (PET) probe derived from octreotide, a metabolically stable somatostatin analog. Octreotide was conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), a chelating agent, and labeled with {sup 68}Gallium ({sup 68}Ga). After intravenous injection of {sup 68}Ga-DOTA-octreotide, a 90-min emission scan of the abdomen was performed in normal and DM model rats. The PET studies showed that {sup 68}Ga-DOTA-octreotide radioactivity was highly accumulated in the pancreas of normal rats and that the pancreatic accumulation was significantly reduced in the rats administered with an excess amount of unlabeled octreotide or after treatment with streptozotocin, which was used for the chemical induction of DM in rats. These results were in good agreement with the ex vivo biodistribution data. These results indicated that the pancreatic accumulation of {sup 68}Ga-DOTA-octreotide represented specific binding to the somatostatin receptors and reflected BCM. Therefore, PET imaging with {sup 68}Ga-DOTA-octreotide could be a potential tool for evaluating BCM.

  16. Challenges in Using Analogies

    Science.gov (United States)

    Lin, Shih-Yin; Singh, Chandralekha

    2011-01-01

    Learning physics requires understanding the applicability of fundamental principles in a variety of contexts that share deep features. One way to help students learn physics is via analogical reasoning. Students can be taught to make an analogy between situations that are more familiar or easier to understand and another situation where the same…

  17. Hydraulic Capacitor Analogy

    Science.gov (United States)

    Baser, Mustafa

    2007-01-01

    Students have difficulties in physics because of the abstract nature of concepts and principles. One of the effective methods for overcoming students' difficulties is the use of analogies to visualize abstract concepts to promote conceptual understanding. According to Iding, analogies are consistent with the tenets of constructivist learning…

  18. Electrostatic analogy for symmetron gravity

    Science.gov (United States)

    Ogden, Lillie; Brown, Katherine; Mathur, Harsh; Rovelli, Kevin

    2017-12-01

    The symmetron model is a scalar-tensor theory of gravity with a screening mechanism that suppresses the effect of the symmetron field at high densities characteristic of the Solar System and laboratory scales but allows it to act with gravitational strength at low density on the cosmological scale. We elucidate the screening mechanism by showing that in the quasistatic Newtonian limit there are precise analogies between symmetron gravity and electrostatics for both strong and weak screening. For strong screening we find that large dense bodies behave in a manner analogous to perfect conductors in electrostatics. Based on this analogy we find that the symmetron field exhibits a lightning rod effect wherein the field gradients are enhanced near the ends of pointed or elongated objects. An ellipsoid placed in a uniform symmetron gradient is shown to experience a torque. By symmetry there is no gravitational torque in this case. Hence this effect unmasks the symmetron and might serve as the basis for future laboratory experiments. The symmetron force between a point mass and a large dense body includes a component corresponding to the interaction of the point mass with its image in the larger body. None of these effects have counterparts in the Newtonian limit of Einstein gravity. We discuss the similarities between symmetron gravity and the chameleon model as well as the differences between the two.

  19. Optical analogy. Synthesis report

    International Nuclear Information System (INIS)

    1965-01-01

    The authors report the study of conditions under which light attenuation (reflection, diffusion, absorption) and the attenuation of some radiations (notably thermal neutrons) can be described with analogical calculations. The analogy between light physical properties and neutron properties is not searched for, but the analogy between their attenuation characteristics. After having discussed this possible analogy, they propose a mathematical formulation of neutron and optical phenomena which could theoretically justify the optical analogy. The second part reports a more practical study of optics problems such as the study of simple optics materials and illumination measurements, or more precisely the study of angular distributions of optical reflections, a determination of such angular distributions, and an experimental determination of the albedo

  20. Somatostatin-expressing inhibitory interneurons in cortical circuits

    Directory of Open Access Journals (Sweden)

    Iryna Yavorska

    2016-09-01

    Full Text Available Cortical inhibitory neurons exhibit remarkable diversity in their morphology, connectivity, and synaptic properties. Here, we review the function of somatostatin-expressing (SOM inhibitory interneurons, focusing largely on sensory cortex. SOM neurons also comprise a number of subpopulations that can be distinguished by their morphology, input and output connectivity, laminar location, firing properties, and expression of molecular markers. Several of these classes of SOM neurons show unique dynamics and characteristics, such as facilitating synapses, specific axonal projections, intralaminar input, and top-down modulation, which suggest possible computational roles. SOM cells can be differentially modulated by behavioral state depending on their class, sensory system, and behavioral paradigm. The functional effects of such modulation have been studied with optogenetic manipulation of SOM cells, which produces effects on learning and memory, task performance, and the integration of cortical activity. Different classes of SOM cells participate in distinct disinhibitory circuits with different inhibitory partners and in different cortical layers. Through these disinhibitory circuits, SOM cells help encode the behavioral relevance of sensory stimuli by regulating the activity of cortical neurons based on subcortical and intracortical modulatory input. Associative learning leads to long-term changes in the strength of connectivity of SOM cells with other neurons, often influencing the strength of inhibitory input they receive. Thus despite their heterogeneity and variability across cortical areas, current evidence shows that SOM neurons perform unique neural computations, forming not only distinct molecular but also functional subclasses of cortical inhibitory interneurons.

  1. Diagnostic value of somatostatin receptor scintigraphy in patients with intracranial tumours. Diagnostische Wertigkeit der Somatostatin-Rezeptor-Szintigraphie bei Patienten mit intrakraniellen Raumforderungen

    Energy Technology Data Exchange (ETDEWEB)

    Luyken, C. (Klinik fuer Neurochirurgie, Koeln Univ. (Germany)); Hildebrandt, G. (Klinik fuer Neurochirurgie, Koeln Univ. (Germany)); Scheidhauer, K. (Klinik fuer Nuklearmedizin, Koeln Univ. (Germany)); Kirsch, B. (Anatomisches Inst., Kiel Univ. (Germany))

    1993-12-01

    The aim of the study was to detect the SR binding sites in intracranial tumours and to evaluate the benefit of SRS in pre- and postoperative diagnostics. 86 patients with 94 intracranial tumours (39 meningiomas, 18 pituitary adenomas, 11 gliomas grade 3 or 4, 8 gliomas grade 2, 5 neurinomas, 5 intracranial metastases, 4 tumours of the orbit, 2 neurofibromas, 1 brain abscess and 1 cystic lesion) were examined. [sup 111]In-octreotide was injected i.v. as 10 [mu]g or 20 [mu]g bolus, corresponding to 110 or 220 MBq (3 or 6 mCi). Gamma-camera images and SPECT were obtained 3-6 h and 24 h post injection. The scintigraphic evaluation was performed without knowledge of CT and MRI results. The histological classification corresponded to the WHO grading system. Somatostatin binding sites were detected in vito using somatostatin-gold conjugates. All patients with meningiomas showed a high focal tracer uptake corresponding to SR binding sites in vitro, whereas only in 50% of the pituitary adenomas SRS was positive. Neurinomas did not show any tracer uptake. In patients with gliomas with disturbed blood-brain-barrier positive tracer uptake was detected, while none of the gliomas with intact blood-brain-barrier could be visualized by SRS but showed somatostatin binding sites in vitro. In intracranial metastases a local tracer uptake was detected in vivo. In vitro 3 of 4 cases showed somatostatin binding sites. In 2 cases extracranial tracer uptake showed the primary tumour and metastases of the lymphnodes. Somatostatin receptor scintigraphy can help to detect or to exclude meningiomas especially in the cerebellopontine angle or in the orbit. In intracranial metastases SRS may point to the primary tumour or other metastases. In all other intracranial tumours receptor scintigraphy provides no clinical relevant information. (orig./MG)

  2. Influence of PET/CT 68Ga somatostatin receptor imaging on proceeding with patients, who were previously diagnosed with 99mTc-EDDA/HYNIC-TOC SPECT.

    Science.gov (United States)

    Madrzak, Dorota; Mikołajczak, Renata; Kamiński, Grzegorz

    2016-01-01

    The aim of this study was the assessment of utility of somatostatin receptor scintigraphy (SRS) by SPECT imaging using 99mTc-EDDA/HYNIC-Tyr3-octreotide (99mTc-EDDA/HYNIC-TOC) in patients with neuroendocrine neoplasm (NEN) or suspected NEN, referred to Nuclear Medicine Dept. of Voivodship Specialty Center in Rzeszow. The selected group of patients was referred also to 68Ga PET/CT. The posed question was the ratio of patients for whom PET/CT with 68Ga would change their management. The distribution of somatostatin receptors was imaged using 99mTc-EDDA/HYNIC-TOC in 61 planar and SPECT studies between 13/05/2010 and 04/02/2013 in Nuclear Medicine Dept. of Voivodship Specialty Center in Rzeszow. The patient age was within a range of 17-80, with the average age of 57.6. The average age of women (65% of patients over-all) was 55.6 and the average age of men (35% of patients overall) was 61.4. In 46 participants (75% of the study group), that underwent SRS, NEN was documented using pathology tests. Selected patients were referred to PET/CT with 68Ga labeled somatostatin analogs, DOTATATE or DOTANOC. This study group consisted of 14 female and 10 male participants with age range of 35-77 and average age of 55.5 years. Patients were classified into 3 groups, as follows: detection - referral due to clinical symptoms and/or biochemical markers (CgA-Chromogranin A, IAA-indoleacetic acid) with the aim of primary diagnosis, staging - referral with the aim of assessment of tumor spread, and follow-up - assessment of the therapy. Out of 61 patients, 24 underwent both 99mTc-EDDA/HYNIC-Tyr3-octreotide SPECT and 68Ga PET/CT. The result of PET/CT was used as a basis for further evaluation. Therefore, the patients were divided into groups; true positive TP (confirmed presence of tissue somatostatin receptors with 68Ga PET/CT) and TN (68Ga PET/CT did not detect any changes and the results were comparable and had the same influence on treatment protocol). In case of SPECT, the results

  3. Effect of somatostatin on nonesterified fatty acid levels modifies glucose homeostasis during fasting

    International Nuclear Information System (INIS)

    Hendrick, G.K.; Frizzell, R.T.; Cherrington, A.D.

    1987-01-01

    In the 7-days fasted conscious dog, unlike the postabsorptive conscious dog, somatostatin infusion results in decreased levels of nonesterified fatty acids (NEFA) and increased glucose utilization (R d ) even when insulin and glucagon levels are held constant. The aim of this study was to determine whether NEFA replacement in such animals would prevent the increase in R d . In each of three protocols there was an 80-min tracer equilibration period, a 40-min basal period, and a 3-h test period. During the test period in the first protocol saline was infused, in the second protocol somatostatin was infused along with intraportal replacement amounts of insulin and glucagon (hormone replacement), while in the third protocol somatostatin plus the pancreatic hormones were infused with concurrent heparin plus Intralipid infusion. Glucose turnover was assessed using [3- 3 H]glucose. The peripheral levels of insulin, glucagon, and glucose were similar and constant in all three protocols; however, during somatostatin infusion, exogenous glucose infusion was necessary to maintain euglycemia. The NEFA level was constant during saline infusion and decreased in the hormone replacement protocol. In the hormone replacement plus NEFA protocol, the NEFA level did not change during the first 90-min period and then increased during the second 90-min period. After a prolonged fast in the dog, (1) somatostatin directly or indirectly inhibits adipose tissue NEFA release and causes a decrease in the plasma NEFA level, and (2) this decrease in the NEFA level causes an increase in R d

  4. Outcome of endoscopic transsphenoidal surgery in combination with somatostatin analogues in patients with growth hormone producing pituitary adenoma.

    Science.gov (United States)

    Zhou, Tao; Wang, Fuyu; Meng, Xianghui; Ba, Jianmin; Wei, Shaobo; Xu, Bainan

    2014-11-01

    To determine the efficacy of endoscopic surgery in combination with long-acting somatostatin analogues (SSAs) in treating patients with growth hormone (GH)-secreting pituitary tumor. We performed retrospective analysis of 133 patients with GH producing pituitary adenoma who underwent pure endoscopic transsphenoidal surgery in our center from January 2007 to July 2012. Patients were followed up for a range of 3-48 months. The radiological remission, biochemical remission and complication were evaluated. A total of 110 (82.7%) patients achieved radiological complete resection, 11 (8.2%) subtotal resection, and 12 (9.0%) partial resection. Eighty-eight (66.2%) patients showed nadir GH level less than 1 ng/mL after oral glucose administration. No mortality or severe disability was observed during follow up. Preoperative long-acting SSA successfully improved left ventricle ejection fraction (LVEF) and blood glucose in three patients who subsequently underwent success operation. Long-acting SSA (20 mg every 30 days) achieved biochemical remission in 19 out 23 (82.6%) patients who showed persistent high GH level after surgery. Endoscopic transsphenoidal surgery can biochemically cure the majority of GH producing pituitary adenoma. Post-operative use of SSA can improve biochemical remission.

  5. Meat analog: a review.

    Science.gov (United States)

    Malav, O P; Talukder, S; Gokulakrishnan, P; Chand, S

    2015-01-01

    The health-conscious consumers are in search of nutritious and convenient food item which can be best suited in their busy life. The vegetarianism is the key for the search of such food which resembles the meat in respect of nutrition and sensory characters, but not of animal origin and contains vegetable or its modified form, this is the point when meat analog evolved out and gets shape. The consumers gets full satisfaction by consumption of meat analog due to its typical meaty texture, appearance and the flavor which are being imparted during the skilled production of meat analog. The supplement of protein in vegetarian diet through meat alike food can be fulfilled by incorporating protein-rich vegetative food grade materials in meat analog and by adopting proper technological process which can promote the proper fabrication of meat analog with acceptable meat like texture, appearance, flavor, etc. The easily available vegetables, cereals, and pulses in India have great advantages and prospects to be used in food products and it can improve the nutritional and functional characters of the food items. The various form and functional characters of food items are available world over and attracts the meat technologists and the food processors to bring some innovativeness in meat analog and its presentation and marketability so that the acceptability of meat analog can be overgrown by the consumers.

  6. Evaluation of (64)Cu-labeled DOTA-D-Phe(1)-Tyr (3)-octreotide ((64)Cu-DOTA-TOC) for imaging somatostatin receptor-expressing tumors.

    Science.gov (United States)

    Hanaoka, Hirofumi; Tominaga, Hideyuki; Yamada, Keiich; Paudyal, Pramila; Iida, Yasuhiko; Watanabe, Shigeki; Paudyal, Bishnuhari; Higuchi, Tetsuya; Oriuchi, Noboru; Endo, Keigo

    2009-08-01

    In-111 ((111)In)-labeled octreotide has been clinically used for imaging somatostatin receptor-positive tumors, and radiolabeled octreotide analogs for positron emission tomography (PET) have been developed. Cu-64 ((64)Cu; half-life, 12.7 h) is an attractive radionuclide for PET imaging and is produced with high specific activity using a small biomedical cyclotron. The aim of this study is to produce and fundamentally examine a (64)Cu-labeled octreotide analog, (64)Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-D: -Phe(1)-Tyr(3)-octreotide ((64)Cu-DOTA-TOC). (64)Cu produced using a biomedical cyclotron was reacted with DOTA-TOC for 30 min at 45 degrees C. The stability of (64)Cu-DOTA-TOC was evaluated in vitro (incubated with serum) and in vivo (blood collected after administration) by HPLC analysis. Biodistribution studies were performed in normal mice by administration of mixed solution of (64)Cu-DOTA-TOC and (111)In-DOTA-TOC and somatostatin receptor-positive U87MG tumor-bearing mice by administration of (64)Cu-DOTA-TOC or (64)Cu-1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid-octreotide ((64)Cu-TETA-OC). The tumor was imaged using (64)Cu-DOTA-TOC, (64)Cu-TETA-OC, and FDG with an animal PET scanner. (64)Cu-DOTA-TOC can be produced in amounts sufficient for clinical study with high radiochemical yield. (64)Cu-DOTA-TOC was stable in vitro, but time-dependent transchelation to protein was observed after injection into mice. In biodistribution studies, the radioactivity of (64)Cu was higher than that of (111)In in all organs except kidney. In tumor-bearing mice, (64)Cu-DOTA-TOC showed a high accumulation in the tumor, and the tumor-to-blood ratio reached as high as 8.81 +/- 1.17 at 6 h after administration. (64)Cu-DOTA-TOC showed significantly higher accumulation in the tumor than (64)Cu-TETA-OC. (64)Cu-DOTA-TOC PET showed a very clear image of the tumor, which was comparable to that of (18)F-FDG PET and very similar to that of (64)Cu

  7. Evaluation of 64Cu-labeled DOTA-D-Phe1-Tyr3-octreotide (64Cu-DOTA-TOC) for imaging somatostatin receptor-expressing tumors

    International Nuclear Information System (INIS)

    Hanaoka, Hirofumi; Tominaga, Hideyuki; Yamada, Keiich

    2009-01-01

    In-111 ( 111 In)-labeled octreotide has been clinically used for imaging somatostatin receptor-positive tumors, and radiolabeled octreotide analogs for positron emission tomography (PET) have been developed. Cu-64 ( 64 Cu; half-life, 12.7 h) is an attractive radionuclide for PET imaging and is produced with high specific activity using a small biomedical cyclotron. The aim of this study is to produce and fundamentally examine a 64 Cu-labeled octreotide analog, 64 Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-D-Phe 1 -Tyr 3 -octreotide ( 64 Cu-DOTA-TOC). 64 Cu produced using a biomedical cyclotron was reacted with DOTA-TOC for 30 min at 45 deg C. The stability of 64 Cu-DOTA-TOC was evaluated in vitro (incubated with serum) and in vivo (blood collected after administration) by high performance liquid chromatography (HPLC) analysis. Biodistribution studies were performed in normal mice by administration of mixed solution of 64 Cu-DOTA-TOC and 111 In-DOTA-TOC and somatostatin receptor-positive U87MG tumor-bearing mice by administration of 64 Cu-DOTA-TOC or 64 Cu-1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid-octreotide ( 64 Cu-TETA-OC). The tumor was imaged using 64 Cu-DOTA-TOC, 64 Cu-TETA-OC, and fluorodeoxyglucose (FDG) with an animal PET scanner. 64 Cu-DOTA-TOC can be produced in amounts sufficient for clinical study with high radiochemical yield. 64 Cu-DOTA-TOC was stable in vitro, but time-dependent transchelation to protein was observed after injection into mice. In biodistribution studies, the radioactivity of 64 Cu was higher than that of 111 In in all organs except kidney. In tumor-bearing mice, 64 Cu-DOTA-TOC showed a high accumulation in the tumor, and the tumor-to-blood ratio reached as high as 8.81±1.17 at 6 h after administration. 64 Cu-DOTA-TOC showed significantly higher accumulation in the tumor than 64 Cu-TETA-OC. 64 Cu-DOTA-TOC PET showed a very clear image of the tumor, which was comparable to that of 18 F-FDG PET and

  8. Troubleshooting analog circuits

    CERN Document Server

    Pease, Robert A

    1991-01-01

    Troubleshooting Analog Circuits is a guidebook for solving product or process related problems in analog circuits. The book also provides advice in selecting equipment, preventing problems, and general tips. The coverage of the book includes the philosophy of troubleshooting; the modes of failure of various components; and preventive measures. The text also deals with the active components of analog circuits, including diodes and rectifiers, optically coupled devices, solar cells, and batteries. The book will be of great use to both students and practitioners of electronics engineering. Other

  9. Pertussis toxin inhibits somatostatin-induced K+ conductance in human pituitary tumor cells

    International Nuclear Information System (INIS)

    Yamashita, N.; Kojima, I.; Shibuya, N.; Ogata, E.

    1987-01-01

    The effect of pertussis toxin on somatostatin-induced K + current was examined in dissociated human pituitary tumor cells obtained from two acromegalic patients. Somatostatin-induced hyperpolarization or K + current was observed in 20 of 23 cells in adenoma 1 and 10 of 11 cells in adenoma 2. After treatment with pertussis toxin for 24 h, these responses were completely suppressed (0/14 in adenoma, 1, 0/10 in adenoma 2). Spontaneous action potentials, K + , Na + , and Ca 2+ currents were well preserved after pertussis toxin treatment. When crude membrane fraction was incubated with [ 32 P]NAD, a 41K protein was ADP-ribosylated by pertussis toxin. Hormone release was inhibited by somatostatin and this inhibition was blocked by pertussis toxin treatment

  10. Somatostatin Receptor Scintigraphy Findings in a Patient with Metastatic Gastrinoma and MEN 1 Syndrome

    Directory of Open Access Journals (Sweden)

    Gözde Mütevelizade

    2011-12-01

    Full Text Available Liver metastases from neuroendocrine tumours frequently occur and significantly worsen their prognosis. Somatostatin receptor scintigraphy (SRS is a valuable method for the detection of somatostatin receptor-positive lesions like gastrinoma. In this case report, the importance of SRS to localize the primary tumor and the spread of disease is emphasized in a patient with neuroendocrine liver metastases. A 45-year-old man was admitted to hospital with multiple liver metastasis of neuroendocrine carcinoma. Somatostatin receptor scintigraphy showed multiple intense radiotracer uptakes in the liver and a focal tracer uptake at the right side of the upper abdominal region corresponding to duodenum or pancreas. Elevated serum gastrin levels confirmed the gastrinoma diagnosis. (MRT 2011;20:117-120

  11. Somatostatin and serum gastrin in normal subjects and in patients with pernicious anaemia, chronic liver and renal disease

    Energy Technology Data Exchange (ETDEWEB)

    Le Roith, D; Vinik, A I; Epstein, S; Baron, P; Olkenitzky, M N; Pimstone, B L

    1975-09-13

    The effects of somatostatin (growth hormone release inhibiting hormone) on basal gastrin were studied in patients suffering from pernicious anaemia and chronic renal and liver disease, and during sequential arginine/insulin-stimulated gastrin release in normal subjects. When basal gastrin concentrations were normal (10-50 pg/ml) in controls and in patients who were in renal and liver failure, somatostatin had no effect on gastrin levels. Raised basal gastrin levels in pernicious anaemia and in 2 cases of chronic renal disease, were significantly inhibited by somatostatin with a half-life (T-half) of 3 to 4 minutes. Arginine infusion caused an insignificant rise in serum gastrin which was unaffected by somatostatin, whereas insulin hypoglycaemia significantly stimulated gastrin release, which was inhibited by somatostatin.

  12. Analog circuits cookbook

    CERN Document Server

    Hickman, Ian

    2013-01-01

    Analog Circuits Cookbook presents articles about advanced circuit techniques, components and concepts, useful IC for analog signal processing in the audio range, direct digital synthesis, and ingenious video op-amp. The book also includes articles about amplitude measurements on RF signals, linear optical imager, power supplies and devices, and RF circuits and techniques. Professionals and students of electrical engineering will find the book informative and useful.

  13. FGF growth factor analogs

    Science.gov (United States)

    Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY; Takahashi, Kazuyuki [Germantown, MD

    2012-07-24

    The present invention provides a fibroblast growth factor heparin-binding analog of the formula: ##STR00001## where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, X, Y and Z are as defined, pharmaceutical compositions, coating compositions and medical devices including the fibroblast growth factor heparin-binding analog of the foregoing formula, and methods and uses thereof.

  14. Development of antibodies against the rat brain somatostatin receptor.

    Science.gov (United States)

    Theveniau, M; Rens-Domiano, S; Law, S F; Rougon, G; Reisine, T

    1992-05-15

    Somatostatin (SRIF) is a neurotransmitter in the brain involved in the regulation of motor activity and cognition. It induces its physiological actions by interacting with receptors. We have developed antibodies against the receptor to investigate its structural properties. Rabbit polyclonal antibodies were generated against the rat brain SRIF receptor. These antibodies (F4) were able to immunoprecipitate solubilized SRIF receptors from rat brain and the cell line AtT-20. The specificity of the interaction of these antibodies with SRIF receptors was further demonstrated by immunoblotting. F4 detected SRIF receptors of 60 kDa from rat brain and adrenal cortex and the cell lines AtT-20, GH3, and NG-108, which express high densities of SRIF receptors. They did not detect immunoreactive material from rat liver or COS-1, HEPG, or CRL cells, which do not express functional SRIF receptors. In rat brain, 60-kDa immunoreactivity was detected by F4 in the hippocampus, cerebral cortex, and striatum, which have high densities of SRIF receptors. However, F4 did not interact with proteins from cerebellum and brain stem, which express few SRIF receptors. Immunoreactive material cannot be detected in rat pancreas or pituitary, which have been reported to express a 90-kDa SRIF receptor subtype. The selective detection of 60-kDa SRIF receptors by F4 indicates that the 60- and 90-kDa SRIF receptor subtypes are immunologically distinct. The availability of antibodies that selectively detect native and denatured brain SRIF receptors provides us with a feasible approach to clone the brain SRIF receptor gene(s).

  15. Somatostatin analogues labelled with 99mTc

    International Nuclear Information System (INIS)

    Obenaus, E.; Crudo, J.; Edreira, M.; Viaggi, M.; De Castiglia, S.G.

    2001-01-01

    The aim of the present work was to study the biological and radiochemical behaviour of two somatostatin analogues, the RC-160 and Tyr3Octreotide(TOC) peptides when labelling with 99m Tc by two methods: direct and indirect using S-benzoyl- mercaptoacetyl triglycine (MAG-3) and hydrazinonicotinamide (HYNIC) as chelating agents. RC-160 was labelled with 125I (30% labelling yield) in order to examine its receptor specificity and to study the biodistribution in normal animals. A total binding of 30% and a non specific binding lower than 10% was obtained. On the other hand, the RC-160 was labelled with 99m Tc by a direct method (70% labelling yield), using sodium ascorbate and dithionite in order to reduce the peptide and 99m Tc, respectively. The synthesis of RC-160 with S-benzoyl MAG-3 and TOC with HYNIC, for labelling with 99m Tc are also described. The conjugates were prepared on a small scale and labelled with the radionuclide using tricine as co-ligands for HYNIC conjugates. Chromatographic studies were performed using HPLC system and radiochemical purities higher than 75% and 95% were obtained respectively. Biodistributions studies in normal Wistar rats were performed and results were correlated with chromatographic and protein binding properties. Lower lipophilicity of the labelled conjugates resulted in a higher renal excretion. HYNIC-TOC complex showed promising results when labelling with 99m Tc using tricine as co-ligand although higher stability should be found for ternary co-ligands compared to tricine. (author)

  16. Clinical value of somatostatin receptor imaging in patients with suspected head and neck paragangliomas

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, Matthias; Dietlein, Markus; Weber, Kerstin; Moka, Detlef; Schicha, Harald [Klinik und Poliklinik fuer Nuklearmedizin, Universitaet zu Koeln, Joseph-Stelzmann-Strasse 9, 50924 Koeln (Germany); Fischer, Eva; Michel, Olaf; Stennert, Eberhard [Klinik und Poliklinik fuer Hals-, Nasen- und Ohrenheilkunde, Universitaet zu Koeln, Koeln (Germany)

    2002-12-01

    Paragangliomas or glomus tumours of the head and neck region are rare somatostatin receptor-expressing neuroendocrine tumours. Precise preoperative diagnosis is of special importance in order to adequately weigh the potential benefit of the operation against the inherent risks of the procedure. In this study, the clinical value of somatostatin receptor imaging was assessed in 19 patients who underwent somatostatin receptor scintigraphy because of known or suspected paraganglioma of the head and neck region. The results were compared with the results of computed tomography and/or magnetic resonance imaging, histology and clinical follow-up. [{sup 111}In-DTPA-D-Phe{sup 1}]-octreotide scintigraphy was performed 4-6 and 24 h after i.v. injection of 140-220 MBq {sup 111}In-octreotide. Whole-body and planar images as well as single-photon emission tomography images were acquired and lesions were graded according to qualitative tracer uptake. Somatostatin receptor imaging was positive in nine patients, identifying paragangliomas for the first time in three patients and recurrent disease in six patients. In one patient, a second, previously unknown paraganglioma site was identified. Negative results were obtained in ten patients. These patients included one suffering from chronic hyperplastic otitis externa, one with granuloma tissue and an organised haematoma, one with an acoustic neuroma, one with an asymmetric internal carotid artery, two with ectasia of the bulbus venae jugularis and one with a jugular vein thrombosis. In two patients with a strong family history of paraganglioma, individual involvement could be excluded. In only one patient did somatostatin receptor imaging and magnetic resonance imaging yield false negative results in respect of recurrent paraganglioma tissue. It is concluded that somatostatin receptor scintigraphy provides important information in patients with suspected paragangliomas of the head and neck region and has a strong impact on further

  17. Electrical Circuits and Water Analogies

    Science.gov (United States)

    Smith, Frederick A.; Wilson, Jerry D.

    1974-01-01

    Briefly describes water analogies for electrical circuits and presents plans for the construction of apparatus to demonstrate these analogies. Demonstrations include series circuits, parallel circuits, and capacitors. (GS)

  18. In vitro comparison of renal handling and uptake of two somatostatin receptor-specific peptides labeled with indium-111

    International Nuclear Information System (INIS)

    Trejtnar, F.; Novy, Z.; Petrik, M.; Laznickova, A.; Melicharova, L.; Vankova, M.; Laznicek, M.

    2008-01-01

    Radiolabeled receptor-specific somatostatin analogs labeled with gamma- or beta-emitting radionuclides are useful for scintigraphic imaging and/or therapy of selected neuroendocrine tumors. However, significant renal uptake may result in radiotoxicological injury of the kidney and can limit clinical application of the agents. The aim of the study was to analyze renal handling, rate, and mechanism of renal accumulation of two somatostatin receptor-targeted peptides, [DOTA 0 , Tyr 3 , Thr 8 ]-octreotide (DOTA-TATE) and [DOTA 0 , 1-Nal 3 ]-octreotide (DOTA-NOC), labeled with indium-111 using in vitro methods. The perfused rat kidney and freshly isolated rat renal cells were used as experimental models. The perfusion was performed in a recirculation regimen at constant pressure with solution containing bovine albumin, erythrocytes, and a mixture of essential substrates. The renal cells were isolated from rat kidneys using two-phase collagenase perfusion. Accumulation studies were used to evaluate the renal uptake of the peptides and to compare their accumulation with that of passively or actively transported model drugs. The influence of selected inhibitors of receptor-mediated endocytosis and the inhibition of energy-dependent transport processes on the uptake were also investigated using isolated renal cells. The renal clearance of 111 In-DOTA-NOC in the perfused rat kidney was significantly lower than that of 111 In-DOTA-TATE. Reverse situation was found in the case of renal retention. Pretreatment of the perfused kidney with maleate markedly decreased the renal retention. 111 In-DOTA-NOC was accumulated in the isolated renal cells at a higher rate than 111 In-DOTA-TATE (ratio 3:1). The uptake of the radiopeptides in renal cells was higher than the uptake of not only the passively transported sucrose but also actively transported and accumulated methylglucose. The rank order of potency to inhibit the uptake by active endocytosis was approximately aprotinin

  19. Insulin analogs with improved pharmacokinetic profiles.

    Science.gov (United States)

    Brange; Vølund

    1999-02-01

    The aim of insulin replacement therapy is to normalize blood glucose in order to reduce the complications of diabetes. The pharmacokinetics of the traditional insulin preparations, however, do not match the profiles of physiological insulin secretion. The introduction of the rDNA technology 20 years ago opened new ways to create insulin analogs with altered properties. Fast-acting analogs are based on the idea that an insulin with less tendency to self-association than human insulin would be more readily absorbed into the systemic circulation. Protracted-acting analogs have been created to mimic the slow, steady rate of insulin secretion in the fasting state. The present paper provides a historical review of the efforts to change the physicochemical and pharmacological properties of insulin in order to improve insulin therapy. The available clinical studies of the new insulins are surveyed and show, together with modeling results, that new strategies for optimal basal-bolus treatment are required for utilization of the new fast-acting analogs.

  20. Novel galeterone analogs act independently of AR and AR-V7 for the activation of the unfolded protein response and induction of apoptosis in the CWR22Rv1 prostate cancer cell model.

    Science.gov (United States)

    McCarty, David J; Huang, Weiliang; Kane, Maureen A; Purushottamachar, Puranik; Gediya, Lalji K; Njar, Vincent C O

    2017-10-24

    The androgen receptor (AR) has long been the primary target for the treatment of prostate cancer (PC). Despite continuous efforts to block AR activity through ligand depletion, AR antagonism, AR depletion and combinations thereof, advanced PC tumors remain resilient. Herein, we evaluate two galeterone analogs, VNPT-178 and VNLG-74A, in PC cell models of diverse androgen and AR dependence attempting to delineate their mechanisms of action and potential clinical utility. Employing basic biochemical techniques, we determined that both analogs have improved antiproliferative and anti-AR activities compared to FDA-approved abiraterone and enzalutamide. However, induction of apoptosis in these models is independent of the AR and its truncated variant, AR-V7, and instead likely results from sustained endoplasmic reticulum stress and deregulated calcium homeostasis. Using in silico molecular docking, we predict VNPT-178 and VNLG-74A bind the ATPase domain of BiP/Grp78 and Hsp70-1A with greater affinity than the AR. Disruption of 70 kDa heat shock protein function may be the underlying mechanism of action for these galeterone analogs. Therefore, despite simultaneously antagonizing AR activity, AR and/or AR-V7 expression alone may inadequately predict a patient's response to treatment with VNPT-178 or VNLG-74A. Future studies evaluating the context-specific limitations of these compounds may provide clarity for their clinical application.

  1. CMOS analog circuit design

    CERN Document Server

    Allen, Phillip E

    1987-01-01

    This text presents the principles and techniques for designing analog circuits to be implemented in a CMOS technology. The level is appropriate for seniors and graduate students familiar with basic electronics, including biasing, modeling, circuit analysis, and some familiarity with frequency response. Students learn the methodology of analog integrated circuit design through a hierarchically-oriented approach to the subject that provides thorough background and practical guidance for designing CMOS analog circuits, including modeling, simulation, and testing. The authors' vast industrial experience and knowledge is reflected in the circuits, techniques, and principles presented. They even identify the many common pitfalls that lie in the path of the beginning designer--expert advice from veteran designers. The text mixes the academic and practical viewpoints in a treatment that is neither superficial nor overly detailed, providing the perfect balance.

  2. Analogical Reasoning in Geometry Education

    Science.gov (United States)

    Magdas, Ioana

    2015-01-01

    The analogical reasoning isn't used only in mathematics but also in everyday life. In this article we approach the analogical reasoning in Geometry Education. The novelty of this article is a classification of geometrical analogies by reasoning type and their exemplification. Our classification includes: analogies for understanding and setting a…

  3. Digital and analog communication systems

    Science.gov (United States)

    Shanmugam, K. S.

    1979-01-01

    The book presents an introductory treatment of digital and analog communication systems with emphasis on digital systems. Attention is given to the following topics: systems and signal analysis, random signal theory, information and channel capacity, baseband data transmission, analog signal transmission, noise in analog communication systems, digital carrier modulation schemes, error control coding, and the digital transmission of analog signals.

  4. High sensitivity of the in vivo detection of somatostatin receptors by 111Indium (DTPA-Octreotide)-scintigraphy in meningioma patients

    International Nuclear Information System (INIS)

    Hildebrandt, G.; Luyken, C.; Klug, N.; Scheidhauer, K.; Schicha, H.; Dahms, P.; Krisch, B.

    1994-01-01

    The recent availability of isotope-labelled somatostatin analogues has allowed one to detect somatostatin receptors in normal tissue as well as in endocrine or non-endocrine cranial tumours. The purpose of the present study was to establish the value of somatostatin receptor scintigraphy using an 111 indium-labelled somatostatin analogue, octreotide, in the diagnostic work-up of meningioma patients. Twenty-two patients (16 women, 6 men, aged from 19-70 years) with newly diagnosed, residual or recurrent cranial meningiomas were examined. 111 indium-labelled DTPA-octreotide was injected i.v.. Planar and tomographic images were obtained with a gamma camera 4-6, and 24 hours after injection. In all of the meningiomas studies a high density of somatostatin receptor was detected by scintigraphy. No false negative test result was found. Due to this, a 100% predictive value of a negative test was calculated. However, when the tumours were taken in culture differing staining intensity could be seen in the light- and electron microscopic level even on individual cells of a single culture when silver intensified somatostatin-gold was used as ligand. We conclude, that in vivo somatostatin receptor scintigraphy may aid in the pre-operative differential diagnosis of skull base tumours

  5. Role of somatostatin receptor-2 in gentamicin-induced auditory hair cell loss in the Mammalian inner ear.

    Directory of Open Access Journals (Sweden)

    Yves Brand

    Full Text Available Hair cells and spiral ganglion neurons of the mammalian auditory system do not regenerate, and their loss leads to irreversible hearing loss. Aminoglycosides induce auditory hair cell death in vitro, and evidence suggests that phosphatidylinositol-3-kinase/Akt signaling opposes gentamicin toxicity via its downstream target, the protein kinase Akt. We previously demonstrated that somatostatin-a peptide with hormone/neurotransmitter properties-can protect hair cells from gentamicin-induced hair cell death in vitro, and that somatostatin receptors are expressed in the mammalian inner ear. However, it remains unknown how this protective effect is mediated. In the present study, we show a highly significant protective effect of octreotide (a drug that mimics and is more potent than somatostatin on gentamicin-induced hair cell death, and increased Akt phosphorylation in octreotide-treated organ of Corti explants in vitro. Moreover, we demonstrate that somatostatin receptor-1 knockout mice overexpress somatostatin receptor-2 in the organ of Corti, and are less susceptible to gentamicin-induced hair cell loss than wild-type or somatostatin-1/somatostatin-2 double-knockout mice. Finally, we show that octreotide affects auditory hair cells, enhances spiral ganglion neurite number, and decreases spiral ganglion neurite length.

  6. Analogs for transuranic elements

    International Nuclear Information System (INIS)

    Weimer, W.C.; Laul, J.C.; Kutt, J.C.

    1981-01-01

    A combined theoretical and experimental approach is being used to estimate the long-term environmental and biogeochemical behaviors of selected transuranic elements. The objective of this research is to estimate the effect that long-term (hundreds of years) environmental weathering has on the behavior of the transuranic elements americium and curium. This is achieved by investigating the actual behavior of naturally occurring rare earth elements, especially neodymium, that serve as transuranic analogs. Determination of the analog element behavior provides data that can be used to estimate the ultimate availability to man of transuranic materials released into the environment

  7. Critical role of somatostatin receptor 2 in the vulnerability of the central noradrenergic system

    DEFF Research Database (Denmark)

    Ádori, Csaba; Glück, Laura; Barde, Swapnali

    2015-01-01

    Alzheimer’s disease and other age-related neurodegenerative disorders are associated with deterioration of the noradrenergic locus coeruleus (LC), a probable trigger for mood and memory dysfunction. LC noradrenergic neurons exhibit particularly high levels of somatostatin binding sites. This is n......Alzheimer’s disease and other age-related neurodegenerative disorders are associated with deterioration of the noradrenergic locus coeruleus (LC), a probable trigger for mood and memory dysfunction. LC noradrenergic neurons exhibit particularly high levels of somatostatin binding sites...... morphometry and mRNA profiling in a cohort of Alzheimer’s and age-matched control brains in combination with genetic models of somatostatin receptor deficiency to establish causality between defunct somatostatin signalling and noradrenergic neurodegeneration. In Alzheimer’s disease, we found significantly....../IV and onwards, i.e., a process preceding advanced Alzheimer’s pathology. The loss of SSTR2 transcripts in the LC neurons appeared selective, since tyrosine hydroxylase, dopamine β-hydroxylase, galanin or galanin receptor 3 mRNAs remained unchanged. We modeled these pathogenic changes in Sstr2 −/− mice and...

  8. Unique functional properties of somatostatin-expressing GABAergic neurons in mouse barrel cortex.

    NARCIS (Netherlands)

    Gentet, L.J.; Kremer, Y.; Taniguchi, H.; Huang, Z.J.; Staiger, J.F.; Petersen, C.C.H.

    2012-01-01

    Neocortical GABAergic neurons have diverse molecular, structural and electrophysiological features, but the functional correlates of this diversity are largely unknown. We found unique membrane potential dynamics of somatostatin-expressing (SOM) neurons in layer 2/3 of the primary somatosensory

  9. Effect of somatostatin on glucose homeostasis in conscious long-fasted dogs

    International Nuclear Information System (INIS)

    Stevenson, R.W.; Steiner, K.E.; Hendrick, G.K.; Cherrington, A.D.

    1987-01-01

    The effects of somatostatin plus intraportal insulin and glucagon replacement (pancreatic clamp) on carbohydrate metabolism were studied in conscious dogs fasted for 7 days so that gluconeogenesis was a major contributor to total glucose production. By use of [3- 3 H]glucose, glucose production (R a ) and utilization (R d ) and glucose clearance were assessed before and after implementation of the pancreatic clamp. After an initial control period, somatostatin (0.8 μg·kg -1 ·min -1 ) was infused with intraportal replacement amounts of glucagon and insulin. The insulin infusion rate was varied to maintain euglycemia and then kept constant for 250 min. Plasma glucagon was similar before and during somatostatin infusion, while plasma insulin was lower. Plasma glucose levels remained similar while R a and R d and the ratio of glucose clearance to plasma insulin were significantly increased. Net hepatic lactate uptake and [ 14 C]alanine plus [ 14 C]lactate conversion to [ 14 C]glucose increased. In conclusion, somatostatin alters glucose clearance in 7-day fasted dogs, resulting in changes in several indices of carbohydrate metabolism

  10. Somatostatin in the rat periventricular nucleus: sex differences and effect of gonadal steroids

    NARCIS (Netherlands)

    Vugt, van H.H.; Heijning, van de B.J.M.; Beek, van der E.M.

    2008-01-01

    In the rat, the sexual dimorphism in growth hormone release is driven by sex steroids, and is suggested to result mainly from differences in somatostatin (SOM) release patterns from the median eminence. We studied the effect of gonadal steroids on SOM peptide-containing cells in the periventricular

  11. Tissue-type plasminogen activator in somatostatin cells of rat pancreas and hypothalamus

    DEFF Research Database (Denmark)

    Kristensen, P; Larsson, L I; Danø, K

    1987-01-01

    -PA, and immunoblotting analysis demonstrated one band with a similar electrophoretic mobility. No urokinase-type PA immunoreactivity was found in the rat endocrine pancreas. A granular t-PA immunoreactivity resembling that found in adjacent sections with somatostatin antiserum was found in the median eminence...

  12. Diagnostic value of somatostatin receptor scintigraphy in patients with intracranial tumours

    International Nuclear Information System (INIS)

    Luyken, C.; Hildebrandt, G.; Scheidhauer, K.; Kirsch, B.

    1993-01-01

    The aim of the study was to detect the SR binding sites in intracranial tumours and to evaluate the benefit of SRS in pre- and postoperative diagnostics. 86 patients with 94 intracranial tumours (39 meningiomas, 18 pituitary adenomas, 11 gliomas grade 3 or 4, 8 gliomas grade 2, 5 neurinomas, 5 intracranial metastases, 4 tumours of the orbit, 2 neurofibromas, 1 brain abscess and 1 cystic lesion) were examined. 111 In-octreotide was injected i.v. as 10 μg or 20 μg bolus, corresponding to 110 or 220 MBq (3 or 6 mCi). Gamma-camera images and SPECT were obtained 3-6 h and 24 h post injection. The scintigraphic evaluation was performed without knowledge of CT and MRI results. The histological classification corresponded to the WHO grading system. Somatostatin binding sites were detected in vito using somatostatin-gold conjugates. All patients with meningiomas showed a high focal tracer uptake corresponding to SR binding sites in vitro, whereas only in 50% of the pituitary adenomas SRS was positive. Neurinomas did not show any tracer uptake. In patients with gliomas with disturbed blood-brain-barrier positive tracer uptake was detected, while none of the gliomas with intact blood-brain-barrier could be visualized by SRS but showed somatostatin binding sites in vitro. In intracranial metastases a local tracer uptake was detected in vivo. In vitro 3 of 4 cases showed somatostatin binding sites. In 2 cases extracranial tracer uptake showed the primary tumour and metastases of the lymphnodes. Somatostatin receptor scintigraphy can help to detect or to exclude meningiomas especially in the cerebellopontine angle or in the orbit. In intracranial metastases SRS may point to the primary tumour or other metastases. In all other intracranial tumours receptor scintigraphy provides no clinical relevant information. (orig./MG) [de

  13. Terrestrial Analogs to Mars

    Science.gov (United States)

    Farr, T. G.; Arcone, S.; Arvidson, R. W.; Baker, V.; Barlow, N. G.; Beaty, D.; Bell, M. S.; Blankenship, D. D.; Bridges, N.; Briggs, G.; Bulmer, M.; Carsey, F.; Clifford, S. M.; Craddock, R. A.; Dickerson, P. W.; Duxbury, N.; Galford, G. L.; Garvin, J.; Grant, J.; Green, J. R.; Gregg, T. K. P.; Guinness, E.; Hansen, V. L.; Hecht, M. H.; Holt, J.; Howard, A.; Keszthelyi, L. P.; Lee, P.; Lanagan, P. D.; Lentz, R. C. F.; Leverington, D. W.; Marinangeli, L.; Moersch, J. E.; Morris-Smith, P. A.; Mouginis-Mark, P.; Olhoeft, G. R.; Ori, G. G.; Paillou, P.; Reilly, J. F., II; Rice, J. W., Jr.; Robinson, C. A.; Sheridan, M.; Snook, K.; Thomson, B. J.; Watson, K.; Williams, K.; Yoshikawa, K.

    2002-08-01

    It is well recognized that interpretations of Mars must begin with the Earth as a reference. The most successful comparisons have focused on understanding geologic processes on the Earth well enough to extrapolate to Mars' environment. Several facets of terrestrial analog studies have been pursued and are continuing. These studies include field workshops, characterization of terrestrial analog sites, instrument tests, laboratory measurements (including analysis of Martian meteorites), and computer and laboratory modeling. The combination of all these activities allows scientists to constrain the processes operating in specific terrestrial environments and extrapolate how similar processes could affect Mars. The Terrestrial Analogs for Mars Community Panel has considered the following two key questions: (1) How do terrestrial analog studies tie in to the Mars Exploration Payload Assessment Group science questions about life, past climate, and geologic evolution of Mars, and (2) How can future instrumentation be used to address these questions. The panel has considered the issues of data collection, value of field workshops, data archiving, laboratory measurements and modeling, human exploration issues, association with other areas of solar system exploration, and education and public outreach activities.

  14. Reasoning through Instructional Analogies

    Science.gov (United States)

    Kapon, Shulamit; diSessa, Andrea A.

    2012-01-01

    This article aims to account for students' assessments of the plausibility and applicability of analogical explanations, and individual differences in these assessments, by analyzing properties of students' underlying knowledge systems. We developed a model of explanation and change in explanation focusing on knowledge elements that provide a…

  15. The Paradox of Analogy

    Directory of Open Access Journals (Sweden)

    David Botting

    2012-03-01

    Full Text Available I will show that there is a type of analogical reasoning that instantiates a pattern of reasoning in confirmation theory that is considered at best paradoxical and at worst fatal to the entire syntactical approach to confirmation and explanation. However, I hope to elaborate conditions under which this is a sound (although not necessarily strong method of reasoning.

  16. Analogy, explanation, and proof

    Science.gov (United States)

    Hummel, John E.; Licato, John; Bringsjord, Selmer

    2014-01-01

    People are habitual explanation generators. At its most mundane, our propensity to explain allows us to infer that we should not drink milk that smells sour; at the other extreme, it allows us to establish facts (e.g., theorems in mathematical logic) whose truth was not even known prior to the existence of the explanation (proof). What do the cognitive operations underlying the inference that the milk is sour have in common with the proof that, say, the square root of two is irrational? Our ability to generate explanations bears striking similarities to our ability to make analogies. Both reflect a capacity to generate inferences and generalizations that go beyond the featural similarities between a novel problem and familiar problems in terms of which the novel problem may be understood. However, a notable difference between analogy-making and explanation-generation is that the former is a process in which a single source situation is used to reason about a single target, whereas the latter often requires the reasoner to integrate multiple sources of knowledge. This seemingly small difference poses a challenge to the task of marshaling our understanding of analogical reasoning to understanding explanation. We describe a model of explanation, derived from a model of analogy, adapted to permit systematic violations of this one-to-one mapping constraint. Simulation results demonstrate that the resulting model can generate explanations for novel explananda and that, like the explanations generated by human reasoners, these explanations vary in their coherence. PMID:25414655

  17. Quantum Analog Computing

    Science.gov (United States)

    Zak, M.

    1998-01-01

    Quantum analog computing is based upon similarity between mathematical formalism of quantum mechanics and phenomena to be computed. It exploits a dynamical convergence of several competing phenomena to an attractor which can represent an externum of a function, an image, a solution to a system of ODE, or a stochastic process.

  18. Synthesis and optimization of novel allylated mono-carbonyl analogs of curcumin (MACs) act as potent anti-inflammatory agents against LPS-induced acute lung injury (ALI) in rats.

    Science.gov (United States)

    Zhu, Heping; Xu, Tingting; Qiu, Chenyu; Wu, Beibei; Zhang, Yali; Chen, Lingfeng; Xia, Qinqin; Li, Chenglong; Zhou, Bin; Liu, Zhiguo; Liang, Guang

    2016-10-04

    A series of novel symmetric and asymmetric allylated mono-carbonyl analogs of curcumin (MACs) were synthesized using an appropriate synthetic route and evaluated experimentally thru the LPS-induced expression of TNF-α and IL-6. Most of the obtained compounds exhibited improved water solubility as a hydrochloride salt compared to lead molecule 8f. The most active compound 7a was effective in reducing the Wet/Dry ratio in the lungs and protein concentration in bronchoalveolar lavage fluid. Meanwhile, 7a also inhibited mRNA expression of several inflammatory cytokines, including TNF-α, IL-6, IL-1β, and VCAM-1, in Beas-2B cells after Lipopolysaccharide (LPS) challenge. These results suggest that 7a could be therapeutically beneficial for use as an anti-inflammatory agent in the clinical treatment of acute lung injury (ALI). Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  19. Effect of vasoactive intestinal polypeptide and somatostatin on secretion of epidermal growth factor and bicarbonate from Brunner's glands

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier

    1984-01-01

    The effect of VIP and somatostatin on secretion of epidermal growth factor and bicarbonate from Brunner's glands was investigated in the rat. Vasoactive intestinal polypeptide infused in doses of 10 and 100 ng/kg/h significantly increased epidermal growth factor and bicarbonate output......, but the concentrations did not change. Somatostatin infused at doses of 1, 10, 100 and 1000 ng/kg/h against a background of VIP 100 ng/kg/h inhibited in dose-dependent fashion the stimulated epidermal growth factor and bicarbonate outputs from rat Brunner's gland pouches. Also basal secretion was inhibited...... growth factor and bicarbonate from Brunner's glands, an effect which is inhibited by somatostatin. A possible role for somatostatin in the control of Brunner's gland secretion is suggested....

  20. Terrestrial Spaceflight Analogs: Antarctica

    Science.gov (United States)

    Crucian, Brian

    2013-01-01

    Alterations in immune cell distribution and function, circadian misalignment, stress and latent viral reactivation appear to persist during Antarctic winterover at Concordia Station. Some of these changes are similar to those observed in Astronauts, either during or immediately following spaceflight. Others are unique to the Concordia analog. Based on some initial immune data and environmental conditions, Concordia winterover may be an appropriate analog for some flight-associated immune system changes and mission stress effects. An ongoing smaller control study at Neumayer III will address the influence of the hypoxic variable. Changes were observed in the peripheral blood leukocyte distribution consistent with immune mobilization, and similar to those observed during spaceflight. Alterations in cytokine production profiles were observed during winterover that are distinct from those observed during spaceflight, but potentially consistent with those observed during persistent hypobaric hypoxia. The reactivation of latent herpesviruses was observed during overwinter/isolation, that is consistently associated with dysregulation in immune function.

  1. Analog storage integrated circuit

    Science.gov (United States)

    Walker, J.T.; Larsen, R.S.; Shapiro, S.L.

    1989-03-07

    A high speed data storage array is defined utilizing a unique cell design for high speed sampling of a rapidly changing signal. Each cell of the array includes two input gates between the signal input and a storage capacitor. The gates are controlled by a high speed row clock and low speed column clock so that the instantaneous analog value of the signal is only sampled and stored by each cell on coincidence of the two clocks. 6 figs.

  2. Analogy, Explanation, and Proof

    Directory of Open Access Journals (Sweden)

    John eHummel

    2014-11-01

    Full Text Available People are habitual explanation generators. At its most mundane, our propensity to explain allows us to infer that we should not drink milk that smells sour; at the other extreme, it allows us to establish facts (e.g., theorems in mathematical logic whose truth was not even known prior to the existence of the explanation (proof. What do the cognitive operations underlying the (inductive inference that the milk is sour have in common with the (deductive proof that, say, the square root of two is irrational? Our ability to generate explanations bears striking similarities to our ability to make analogies. Both reflect a capacity to generate inferences and generalizations that go beyond the featural similarities between a novel problem and familiar problems in terms of which the novel problem may be understood. However, a notable difference between analogy-making and explanation-generation is that the former is a process in which a single source situation is used to reason about a single target, whereas the latter often requires the reasoner to integrate multiple sources of knowledge. This small-seeming difference poses a challenge to the task of marshaling our understanding of analogical reasoning in the service of understanding explanation. We describe a model of explanation, derived from a model of analogy, adapted to permit systematic violations of this one-to-one mapping constraint. Simulation results demonstrate that the resulting model can generate explanations for novel explananda and that, like the explanations generated by human reasoners, these explanations vary in their coherence.

  3. The future of vitamin D analogs

    Directory of Open Access Journals (Sweden)

    Carlien eLeyssens

    2014-04-01

    Full Text Available The active form of vitamin D3, 1,25-dihydroxyvitamin D3, is a major regulator of bone and calcium homeostasis. In addition, this hormone also inhibits the proliferation and stimulates the differentiation of normal as well as malignant cells. Supraphysiological doses of 1,25-dihydroxyvitamin D3 are required to reduce cancer cell proliferation. However, these doses will lead in vivo to calcemic side effects such as hypercalcemia and hypercalciuria. During the last 25 years, many structural analogs of 1,25-dihydroxyvitamin D3 have been synthesized by the introduction of chemical modifications in the A-ring, central CD-ring region or side chain of 1,25-dihydroxyvitamin D3 in the hope to find molecules with a clear dissociation between the beneficial antiproliferative effects and adverse calcemic side effects. One example of such an analog with a good dissociation ratio is calcipotriol (DaivonexR, which is clinically used to treat the hyperproliferative skin disease psoriasis. Other vitamin D analogs were clinically approved for the treatment of osteoporosis or secondary hyperparathyroidism. No vitamin D analog is currently used in the clinic for the treatment of cancer although several analogs have been shown to be potent drugs in animal models of cancer. Omics studies as well as in vitro cell biological experiments unraveled basic mechanisms involved in the antineoplastic effects of vitamin D and its analogs. 1,25-dihydroxyvitamin D3 and analogs act in a cell type- and tissue-specific manner. Moreover, a blockade in the transition of the G0/1 towards S phase of the cell cycle, induction of apoptosis, inhibition of migration and invasion of tumor cells together with effects on angiogenesis and inflammation have been implicated in the pleiotropic effects of 1,25-dihydroxyvitamin D3 and its analogs. In this review we will give an overview of the action of vitamin D analogs in tumor cells and look forward how these compounds could be introduced in the

  4. Somatostatin receptor scintigraphy in advanced renal cell carcinoma. Results of a phase II-trial of somatostatine analogue therapy in patients with advanced RCC

    International Nuclear Information System (INIS)

    Freudenberg, L.S.; Goerges, R.; Stergar, H.; Bockisch, A.; Gauler, T.; Bauer, S.; Antoch, G.; Schuette, J.

    2008-01-01

    Aims: objective of this prospective study was to evaluate the role of somatostatin receptor scintigraphy (SRS) in advanced renal cell carcinoma (RCC) with respect to potential therapy with somatostatin analogue (SST-A) and to assess the response rate under therapy with SST-A. Patients, methods: 16 patients with documented progression of histologically confirmed advanced RCC were included. Planar whole-body SRS was performed 4, 24 and 48h post i.v. injection of 175-200 MBq 111 In-pentetreoide. 5 and 25 h p.i. SPECT of thorax and abdomen were performed. Documentation of somatostatin receptor expression via SRS in > 50% of known tumour lesions was the criteria for treatment start with SST-A (Sandostatin LAR registered -Depot 30mg i.m. every four weeks). Results: in 9/16 of the patients SRS showed at least one metastasis with moderate (n = 5) or intense (n = 4) tracer uptake. Lesion-based SRS evaluation showed only 12.1% (20/165) of all metastases. Most false-negative lesions were located in the lungs. In too patients, the majority of the known metastases was SRS positive and these patients received SST-A therapy. The first radiographic evaluation after a two-month interval showed progressive disease in both patients. Conclusions: we conclude that SRS is of limited value in staging of advanced RCC. In our patients SST-A did not result in a growth control of RCC. Consequently, the use of SST-A in advanced RCC seems to be no relevant therapeutic option. (orig.)

  5. Component Processes in Analogical Reasoning

    Science.gov (United States)

    Sternberg, Robert J.

    1977-01-01

    Describes alternative theoretical positions regarding (a) the component information processes used in analogical reasoning and (b) strategies for combining these processes. Also presents results from three experiments on analogical reasoning. (Author/RK)

  6. Inductive, Analogical, and Communicative Generalization

    Directory of Open Access Journals (Sweden)

    Adri Smaling

    2003-03-01

    Full Text Available Three forms of inductive generalization - statistical generalization, variation-based generalization and theory-carried generalization - are insufficient concerning case-to-case generalization, which is a form of analogical generalization. The quality of case-to-case generalization needs to be reinforced by setting up explicit analogical argumentation. To evaluate analogical argumentation six criteria are discussed. Good analogical reasoning is an indispensable support to forms of communicative generalization - receptive and responsive (participative generalization — as well as exemplary generalization.

  7. Analogical Reasoning and Computer Programming.

    Science.gov (United States)

    Clement, Catherine A.; And Others

    1986-01-01

    A study of correlations between analogical reasoning and Logo programming mastery among female high school students related the results of pretests of analogical reasoning to posttests of programming mastery. A significant correlation was found between analogical reasoning and the ability to write subprocedures for use in several different…

  8. Somatostatin receptors and their ligands in the human immune system

    NARCIS (Netherlands)

    V.A.S.H. Dalm (Virgil)

    2003-01-01

    textabstractMaintenance of homeostasis is essential for survival of the mammalian organism. For a long time it was believed that the different systems in the human body act independently from each other to achieve this goal. However, during the last decades it has become more evident that the

  9. The potential value of somatostatin receptor scintigraphy in medullary thyroid carcinoma

    International Nuclear Information System (INIS)

    Doerr, U.; Bihl, H.; Frank-Raue, K.; Raue, F.; Sautter-Bihl, M.L.; Buhr, H.J.; Guzman, G.; Inst. de Neurocirugia, Investigationes Cerebrales 'Dr Asenjo' Santiago

    1993-01-01

    In a prospective study, ten patients with recurrent medullary thyroid carcinoma (markedly elevated calcitonin levels) were investigated by means of somatostatin receptor scintigraphy (SRS) with 111 In-pentetreotide. Scintigraphically, 30 sites of pathological uptake were found, mostly located in the neck and upper mediastinum. So far, 18 suspected tumour sites underwent histological examination and 14 of them could be verified as metastases of medullary thyroid carcinoma (MTC). The remaining four putative tumour lesions turned out to be false positive scintigraphic findings caused by chronic inflammation and somatostatin receptor positive tumours other than MTC. We conclude that SRS is a promising imaging modality for localization of MTC recurrence and may thus make a contribution to better management of this patient group. (Author)

  10. The potential value of somatostatin receptor scintigraphy in medullary thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Doerr, U.; Bihl, H. (Katharinenhospital, Stuttgart (Germany). Dept. of Nuclear Medicine); Frank-Raue, K.; Raue, F. (Heidelberg Univ. (Germany). Dept. of Internal Medicine); Sautter-Bihl, M.L.; Buhr, H.J. (Staedt. Klinikum, Karlsruhe (Germany). Dept. of Radiooncology and Nuclear Medicine); Guzman, G. (Katherinenhospital, Stuttgart (Germany). Dept. of Nuclear Medicine Inst. de Neurocirugia, Investigationes Cerebrales ' Dr Asenjo' Santiago (Chile). Dept. de Medicina Nuclear)

    1993-06-01

    In a prospective study, ten patients with recurrent medullary thyroid carcinoma (markedly elevated calcitonin levels) were investigated by means of somatostatin receptor scintigraphy (SRS) with [sup 111]In-pentetreotide. Scintigraphically, 30 sites of pathological uptake were found, mostly located in the neck and upper mediastinum. So far, 18 suspected tumour sites underwent histological examination and 14 of them could be verified as metastases of medullary thyroid carcinoma (MTC). The remaining four putative tumour lesions turned out to be false positive scintigraphic findings caused by chronic inflammation and somatostatin receptor positive tumours other than MTC. We conclude that SRS is a promising imaging modality for localization of MTC recurrence and may thus make a contribution to better management of this patient group. (Author).

  11. Analogical scaffolding: Making meaning in physics through representation and analogy

    Science.gov (United States)

    Podolefsky, Noah Solomon

    This work reviews the literature on analogy, introduces a new model of analogy, and presents a series of experiments that test and confirm the utility of this model to describe and predict student learning in physics with analogy. Pilot studies demonstrate that representations (e.g., diagrams) can play a key role in students' use of analogy. A new model of analogy, Analogical Scaffolding, is developed to explain these initial empirical results. This model will be described in detail, and then applied to describe and predict the outcomes of further experiments. Two large-scale (N>100) studies will demonstrate that: (1) students taught with analogies, according to the Analogical Scaffolding model, outperform students taught without analogies on pre-post assessments focused on electromagnetic waves; (2) the representational forms used to teach with analogy can play a significant role in student learning, with students in one treatment group outperforming students in other treatment groups by factors of two or three. It will be demonstrated that Analogical Scaffolding can be used to predict these results, as well as finer-grained results such as the types of distracters students choose in different treatment groups, and to describe and analyze student reasoning in interviews. Abstraction in physics is reconsidered using Analogical Scaffolding. An operational definition of abstraction is developed within the Analogical Scaffolding framework and employed to explain (a) why physicists consider some ideas more abstract than others in physics, and (b) how students conceptions of these ideas can be modeled. This new approach to abstraction suggests novel approaches to curriculum design in physics using Analogical Scaffolding.

  12. Somatostatin Receptor Scintigraphy (SRS) with 99m-Tc HYNIC-TOC

    International Nuclear Information System (INIS)

    Zarlenga, A.C.; Parma, P.; Arashiro, J.; Castiglia, S.; Obenaus, E.

    2002-01-01

    Background: This compound is a synthetic analogue of somatostatin by conjugating the Hydrazinocotinamide (Hynic) to Tyr 3 -Octreotide (Toc) radiolabeling via quelation with 99m Tc. Purpose: We have analyzed the feasibility in detecting neuroendocrine tumors (NET) by somatostatin receptor with 99m Tc Hynic-Toc. Methods: After comparative studies between 99m Tc Hynic-Toc and 111 In (pentetreotide) with excellent correlation, we have performed 48 scintigrams with 99m Tc Hynic-Toc. 35 patients with suspicions of NET were included (19 women, 16 men. Age range 22-75 y). We have performed planar images at 1,2,24 hs and tomographic images at 150 min after intravenous injection of 740 MBq 99m Tc Hynic-Toc. We compare the results with other diagnosis modalities and /or the histopathological findings after biopsy or surgery. Results: True Positive:17; True Negative:11; False Positive: 4; False Negative:3. Specificity=73.3%; Sensitivity=85%; Accuracy=80%; Not adverse effects were observed. Conclusions: 99m Tc Hynic-Toc is not limited availability of the isotope. It is a suitable radiopharmaceutical for in vivo evaluation to define tumor receptor status, staging, and for identification of patients who may benefit from therapy with somatostatin. The tumor uptake at 24 hs allows a better visualization of abdominal tumor sites. Tc Hynic-Toc is an alternative to 111 In-pentetreotide for imaging somatostatin receptor positive tumors. The study was offered to patients whom the scintigraphy with 111 In-pentetreotide offers a diagnosis alternative with high specificity and accessible cost

  13. Translational Advancement of Somatostatin Gene Delivery for Disease Modification and Cognitive Sparing in Intractable Epilepsy

    Science.gov (United States)

    2015-09-01

    seizures. A thoroughly characterized rodent epilepsy model will be used as a platform to test the hypotheses. In this model temporal lobe electrical...expression in the hippocampus resected from a young temporal lobe epilepsy patient. Post-baccalaureate student Andrew Moss has since expanded this project...somatostatin gene delivery persistently reduces seizure severity in a rat model of temporal lobe epilepsy , Gowri Natarajan, Jessica Anne McElroy

  14. Somatostatin receptor scintigraphy - a case report and review of the literature

    International Nuclear Information System (INIS)

    Yamaga, Lilian Yuri Itaya; Belfer, Aron J.; Segal, Amisa

    1997-01-01

    The authors report a case of carcinoid tumor, diagnosed in a 75-year-old male patient, confirmed by laparotomy and anatomo-pathological study. The patient was examined by somatostatin receptor scintigraphy with In-pentetreotide, and correlation was performed with I-MIBG and CT scan. A review of current literature about this new tracer for detection of carcinoid tumor is presented. (author)

  15. Discrete Calculus by Analogy

    CERN Document Server

    Izadi, F A; Bagirov, G

    2009-01-01

    With its origins stretching back several centuries, discrete calculus is now an increasingly central methodology for many problems related to discrete systems and algorithms. The topics covered here usually arise in many branches of science and technology, especially in discrete mathematics, numerical analysis, statistics and probability theory as well as in electrical engineering, but our viewpoint here is that these topics belong to a much more general realm of mathematics; namely calculus and differential equations because of the remarkable analogy of the subject to this branch of mathemati

  16. ESD analog circuits and design

    CERN Document Server

    Voldman, Steven H

    2014-01-01

    A comprehensive and in-depth review of analog circuit layout, schematic architecture, device, power network and ESD design This book will provide a balanced overview of analog circuit design layout, analog circuit schematic development, architecture of chips, and ESD design.  It will start at an introductory level and will bring the reader right up to the state-of-the-art. Two critical design aspects for analog and power integrated circuits are combined. The first design aspect covers analog circuit design techniques to achieve the desired circuit performance. The second and main aspect pres

  17. Somatostatin-IRES-Cre Mice: Between Knockout and Wild-Type?

    Science.gov (United States)

    Viollet, Cécile; Simon, Axelle; Tolle, Virginie; Labarthe, Alexandra; Grouselle, Dominique; Loe-Mie, Yann; Simonneau, Michel; Martel, Guillaume; Epelbaum, Jacques

    2017-01-01

    The neuropeptide somatostatin (SOM) is widely expressed in rodent brain and somatostatin-IRES-Cre (SOM-cre) mouse strains are increasingly used to unravel the physiology of SOM-containing neurons. However, while knock-in targeting strategy greatly improves Cre-Lox system accuracy, recent reports have shown that genomic insertion of Cre construct per se can markedly affect physiological function. We show that Cre transgene insertion into the 3'UTR of the somatostatin gene leads to the selective and massive depletion of endogenous SOM in all tested brain regions. It also strongly impacts SOM-related neuroendocrine responses in a similar manner to what has been reported for SST KO mice: increased corticosterone levels after 30-min restraint stress, decreased amplitude and regularity of ultradian growth hormone secretory patterns accompanied by changes in sexually dimorphic liver gene expression ( serpina1, Cyp2b9, Cyp2a4, Cyp2d9, and Cyp7b1 ). In addition to demonstrating the need for examination of the consequences of Cre transgenesis, these results also reveal how this SOM-cre strain may be a useful tool in studying the functional consequences of moderate to low SOM levels as reported in neurological and psychiatric disorders.

  18. 99mTc-EDDA/HYNIC-TOC somatostatin receptor scintigraphy in daily clinical practice.

    Science.gov (United States)

    Chrapko, Beata Ewa; Nocuń, Anna; Gołebiewska, Renata; Stefaniak, Bogusław; Korobowicz, Elzbieta; Czekajska-Chehab, Elzbieta; Sawicki, Marek; Polkowski, Wojciech Piotr

    2010-04-01

    This study aimed to assess the impact of 99mTc-EDDA/HYNIC-TOC (99mTc-TOC) somatostatin receptor scintigraphy (SRS) in clinical practice. One hundred seventeen patients were divided into 6 groups: 1, initial detection and localization of suspected neuroendocrine tumor (NET); 2, tumor staging before therapy; 3, staging of NET of unknown origin, 4, restaging after surgery of primary tumor; 5, diagnosis of solitary pulmonary nodules (SPNs), and 6, follow-up after "cold" somatostatin analogues treatment. In group 1, clinical suspicions were not confirmed in any of the patients; in group 2, most of the primary lesions showed overexpression of somatostatin receptors (SSRT); in group 3, the primary tumor was not identified in any of the patients; in group 4, recurrences were depicted in 7 out of 47 patients; in group 5, only 1 malignant SPN was detected, and in group 6, regression of primary mass and metastases were seen on follow-up SRS in 1 patient. 99mTc-TOC SRS is useful in staging of SSRT-overexpressing tumors of known and unknown primary origin, as well as in restaging after primary tumor surgery. This method is less effective in detecting suspected NET and assessing SPNs. Further investigation is necessary to evaluate the usefulness of SRS in monitoring patients after biological treatment.

  19. Albert Einstein, Analogizer Extraordinaire

    CERN Multimedia

    CERN. Geneva

    2007-01-01

    Where does deep insight in physics come from? It is tempting to think that it comes from the purest and most precise of reasoning, following ironclad laws of thought that compel the clear mind completely rigidly. And yet the truth is quite otherwise. One finds, when one looks closely at any major discovery, that the greatest of physicists are, in some sense, the most crazily daring and irrational of all physicists. Albert Einstein exemplifies this thesis in spades. In this talk I will describe the key role, throughout Albert Einstein's fabulously creative life, played by wild guesses made by analogy lacking any basis whatsoever in pure reasoning. In particular, in this year of 2007, the centenary of 1907, I will describe how over the course of two years (1905 through 1907) of pondering, Einstein slowly came, via analogy, to understand the full, radical consequences of the equation that he had first discovered and published in 1905, arguably the most famous equation of all time: E = mc2.

  20. Detecting analogical resemblance without retrieving the source analogy.

    Science.gov (United States)

    Kostic, Bogdan; Cleary, Anne M; Severin, Kaye; Miller, Samuel W

    2010-06-01

    We examined whether people can detect analogical resemblance to an earlier experimental episode without being able to recall the experimental source of the analogical resemblance. We used four-word analogies (e.g., robin-nest/beaver-dam), in a variation of the recognition-without-cued-recall method (Cleary, 2004). Participants studied word pairs (e.g., robin-nest) and were shown new word pairs at test, half of which analogically related to studied word pairs (e.g., beaver-dam) and half of which did not. For each test pair, participants first attempted to recall an analogically similar pair from the study list. Then, regardless of whether successful recall occurred, participants were prompted to rate the familiarity of the test pair, which was said to indicate the likelihood that a pair that was analogically similar to the test pair had been studied. Across three experiments, participants demonstrated an ability to detect analogical resemblance without recalling the source analogy. Findings are discussed in terms of their potential relevance to the study of analogical reasoning and insight, as well as to the study of familiarity and recognition memory.

  1. Effect of treatment with depot somatostatin analogue octreotide on primary hyperparathyroidism (PHP) in multiple endocrine neoplasia type 1 (MEN1) patients.

    Science.gov (United States)

    Faggiano, Antongiulio; Tavares, Lidice Brandao; Tauchmanova, Libuse; Milone, Francesco; Mansueto, Gelsomina; Ramundo, Valeria; De Caro, Maria Laura Del Basso; Lombardi, Gaetano; De Rosa, Gaetano; Colao, Annamaria

    2008-11-01

    In patients with multiple endocrine neoplasia type 1 (MEN1), expression of somatostatin receptor (SST) in parathyroid adenomas and effectiveness of therapy with somatostatin analogues on primary hyperparathyroidism (PHP) have been scarcely investigated. To evaluate the effects of depot long acting octreotide (OCT-LAR) in patients with MEN1-related PHP. Eight patients with a genetically confirmed MEN1, presenting both PHP and duodeno-pancreatic neuroendocrine tumours (NET), were enrolled. The initial treatment was OCT-LAR 30 mg every 4 weeks. This therapy was established to stabilize the duodeno-pancreatic NET before to perform parathyroidectomy for PHP. Before OCT-LAR therapy, a SST scintigraphy was performed in all patients. SST subtype 2A immunohistochemistry was performed on parathyroid tumour samples from three patients undergone parathyroidectomy after OCT-LAR therapy. Serum concentrations of PTH, calcium and phosphorus as well as the 24-h urine calcium : creatinine ratio and the renal threshold phosphate concentration were evaluated before and after OCT-LAR. After OCT-LAR therapy, hypercalcaemia and hypercalciuria normalized in 75% and 62.5% of patients, respectively, and serum phosphorus and renal threshold phosphate significantly increased. Serum PTH concentrations significantly decreased in all patients and normalized in two of them. SST subtype 2A immunostaining was found in all parathyroid adenomas investigated, while SST scintigraphy showed a positive parathyroid tumour uptake in three of eight patients (37.5%). Six months of OCT-LAR therapy controlled hypercalcaemia and hypercalciuria in two-thirds of patients with MEN1-related PHP. Direct OCT-LAR effects mediated by binding to SST expression on parathyroid tumour cells are likely the main mechanism to explain the activity of this compound on calcium and phosphorus abnormalities in MEN1 PHP.

  2. Feedback in analog circuits

    CERN Document Server

    Ochoa, Agustin

    2016-01-01

    This book describes a consistent and direct methodology to the analysis and design of analog circuits with particular application to circuits containing feedback. The analysis and design of circuits containing feedback is generally presented by either following a series of examples where each circuit is simplified through the use of insight or experience (someone else’s), or a complete nodal-matrix analysis generating lots of algebra. Neither of these approaches leads to gaining insight into the design process easily. The author develops a systematic approach to circuit analysis, the Driving Point Impedance and Signal Flow Graphs (DPI/SFG) method that does not require a-priori insight to the circuit being considered and results in factored analysis supporting the design function. This approach enables designers to account fully for loading and the bi-directional nature of elements both in the feedback path and in the amplifier itself, properties many times assumed negligible and ignored. Feedback circuits a...

  3. Beginning analog electronics through projects

    CERN Document Server

    Singmin, Andrew

    2001-01-01

    Analog electronics is the simplest way to start a fun, informative, learning program. Beginning Analog Electronics Through Projects, Second Edition was written with the needs of beginning hobbyists and students in mind. This revision of Andrew Singmin's popular Beginning Electronics Through Projects provides practical exercises, building techniques, and ideas for useful electronics projects. Additionally, it features new material on analog and digital electronics, and new projects for troubleshooting test equipment.Published in the tradition of Beginning Electronics Through Projects an

  4. Effects of cysteamine on dopamine-mediated behaviors: evidence for dopamine-somatostatin interactions in the striatum

    Energy Technology Data Exchange (ETDEWEB)

    Martin-Iverson, M.T.; Radke, J.M.; Vincent, S.R.

    1986-06-01

    The effects of prior treatment with cysteamine, a drug which appears to deplete selectively the neuropeptide somatostatin, on apomorphine-induced stereotypy and amphetamine-induced locomotor activity and conditioned place preferences were investigated. Twelve hours following systemic cysteamine injections apomorphine-induced stereotypy was attenuated and striatal somatostatin levels were reduced by half. Systemic cysteamine also decreased the motor stimulant effects of amphetamine, without influencing the rewarding properties as determined by the conditioned place preference procedure. Direct injections of cysteamine into the nucleus accumbens also decreased the locomotor response to amphetamine, and produced a local reduction in somatostatin levels in the accumbens. Cysteamine did not appear to alter monoamine turnover in the striatum after either systemic or intra-accumbens injections. These results suggest that somatostatin in the nucleus accumbens and caudate-putamen modulates the motor, but not the reinforcing properties of dopaminergic drugs, possibly via an action postsynaptic to dopamine-releasing terminals. Furthermore, it is evident from these results that cysteamine is an important tool with which to study the central actions of somatostatin.

  5. Children's Development of Analogical Reasoning: Insights from Scene Analogy Problems

    Science.gov (United States)

    Richland, Lindsey E.; Morrison, Robert G.; Holyoak, Keith J.

    2006-01-01

    We explored how relational complexity and featural distraction, as varied in scene analogy problems, affect children's analogical reasoning performance. Results with 3- and 4-year-olds, 6- and 7-year-olds, 9- to 11-year-olds, and 13- and 14-year-olds indicate that when children can identify the critical structural relations in a scene analogy…

  6. Cyclopentanoid analogs of phosphatidylcholine: susceptibility to phospholipase A2.

    Science.gov (United States)

    Lister, M D; Hancock, A J

    1988-10-01

    Six isomers of dipalmitoylcyclopentanetriol phosphocholine (cyclopentano-lecithin) were tested as potential substrates for phospholipase A2. Since each of these analogs possesses a configuration that mimics a narrow range of conformations of a glycerophospholipid molecule, the analogs were used to assess the enzyme's conformational requirements. Studies showed that all of the analogs containing the phosphocholine at the C-1 (or C-3) position could be hydrolyzed, while only one of the three analogs that contains the polar head group at the C-2 position was susceptible. Kinetic studies, however, revealed that only the all-trans-(1,3/2-1P)-cyclopentano-lecithin gave initial rates of hydrolysis that were measurable by pH-stat. Acyl group specificity of the enzyme towards the all-trans isomer was determined with an analog was acyl groups were distinguishable. The synthesis of this mixed-acid-cyclopentano-PC is described herein. When this analog was enzymatically assayed, results unequivocally showed the enzyme to be specific for C-2 acyl hydrolysis. This specificity, and data showing that the all-trans analog is stereospecifically hydrolyzed, indicate that it is acted on in an analogous manner to dipalmitoylphosphatidylcholine. These studies indicate that although the configuration of the analog is not necessarily a prerequisite for hydrolysis, there does appear to be an optimal spatial orientation for enzymatic activity. The analogy between the susceptibilities of all-trans-(1,3/2-1P)-cyclopentano-lecithin and glycero-lecithin suggests that the conformation of the glycero-lecithin during phospholipase A2-mediated hydrolysis may be best simulated by the all-trans orientation of C-O bonds in the artificial substrate.

  7. Optical analog transmission device

    International Nuclear Information System (INIS)

    Ikawa, Shinji.

    1994-01-01

    The present invention concerns a device such as electro-optical conversion elements, optoelectric-electric elements and optical transmission channel, not undergoing deleterious effects on the efficiency of conversion and transmission due to temperature, and aging change. That is, a sine wave superposing means superposes, on a detector signal to be transmitted, a sine-wave signal having a predetermined amplitude and at a frequency lower than that of the detector signal. An optoelectric conversion means converts the electric signal as the signal of the sine-wave signal superposing means into an optical signal and outputs the same to an optical transmitting channel. The optoelectric conversion means converts the transmitted signal to an electric signal. A discriminating means discriminates the electric signal into a detector signal and a sine-wave signal. A calculating means calculates an optical transmitting efficiency of the transmitting channel based on the amplitude of the discriminated sine-wave signal. A processing means compensates an amplitude value of the detector signals discriminated by the discriminating means based on the optical transmission efficiency. As a result, an optical analog transmission device can be attained, which conducts optical transmission at a high accuracy without undergoing the defective effects of the optical transmission efficiency. (I.S.)

  8. Analysis of transmission of novel polymorphisms in the somatostatin receptor 5 (SSTR5) gene in patients with autism

    DEFF Research Database (Denmark)

    Lauritsen, Marlene B; Nyegaard, Mette; Betancur, Catalina

    2003-01-01

    growth hormone response has been reported in some individuals with autism. Moreover, the somatostatinergic system interacts with the dopaminergic system, which has been hypothesized to be involved in the etiology of autism; in particular, somatostatin secretion is regulated by dopamine, and the dopamine......Infantile autism is a pervasive developmental disorder with a strong genetic component. The mode of inheritance appears to be complex and no specific susceptibility genes have yet been identified. Chromosome 16p13.3 may contain a susceptibility gene based on findings from genome scans and reports...... of chromosome abnormalities in individuals with autism. The somatostatin receptor 5 (SSTR5) gene is located on chromosome 16p13.3 and is thus a positional candidate gene for autism. SSTR5 may also be a functional candidate gene for autism because somatostatin inhibits growth hormone secretion, and increased...

  9. DOTA-derivatives of octreotide dicarba-analogues with high affinity for somatostatin sst2,5 receptors

    Science.gov (United States)

    Pratesi, Alessandro; Ginanneschi, Mauro; Lumini, Marco; Papini, Anna M.; Novellino, Ettore; Brancaccio, Diego; Carotenuto, Alfonso

    2017-02-01

    In vivo somatostatin receptor scintigraphy is a valuable method for the visualization of human endocrine tumours and their metastases. In fact, peptide ligands of somatostatin receptors (sst’s) conjugated with chelating agents are in clinical use. We have recently developed octreotide dicarba-analogues, which show interesting binding profiles at sst’s. In this context, it was mandatory to explore the possibility that our analogues could maintain their activity also upon conjugation with DOTA. In this paper, we report and discuss the synthesis, binding affinity and conformational preferences of three DOTA-conjugated dicarba-analogues of octreotide. Interestingly, two conjugated analogues exhibited nanomolar affinities on sst2 and sst5 somatostatin receptor subtypes.

  10. Conjecturing via Reconceived Classical Analogy

    Science.gov (United States)

    Lee, Kyeong-Hwa; Sriraman, Bharath

    2011-01-01

    Analogical reasoning is believed to be an efficient means of problem solving and construction of knowledge during the search for and the analysis of new mathematical objects. However, there is growing concern that despite everyday usage, learners are unable to transfer analogical reasoning to learning situations. This study aims at facilitating…

  11. Musik som analogi og metafor

    DEFF Research Database (Denmark)

    Bonde, Lars Ole

    2014-01-01

    Indeholder underkapitlerne: 2.5.1 Musik som analogi 2.5.2 Musik som metafor 2.5.3 Musikkens psykologiske funktioner - en taxonomi og metaforisk lytning til fire baroksatser......Indeholder underkapitlerne: 2.5.1 Musik som analogi 2.5.2 Musik som metafor 2.5.3 Musikkens psykologiske funktioner - en taxonomi og metaforisk lytning til fire baroksatser...

  12. Drawing Analogies in Environmental Education

    Science.gov (United States)

    Affifi, Ramsey

    2014-01-01

    Reconsidering the origin, process, and outcomes of analogy-making suggests practices for environmental educators who strive to disengage humans from the isolating illusions of dichotomizing frameworks. We can view analogies as outcomes of developmental processes within which human subjectivity is but an element, threading our sense of self back…

  13. Regulation of ATP-sensitive K+ channels in insulinoma cells: Activation by somatostatin and protein kinase C and the role of cAMP

    International Nuclear Information System (INIS)

    De Weille, J.R.; Schmid-Antomarchi, H.; Fosset, M.; Lazdunski, M.

    1989-01-01

    The actions of somatostatin and of the phorbol ester 4β-phorbol 12-myristate 13-acetate (PMA) were studied in rat insulinoma (RINm5F) cells by electrophysiological and 86 Rb + flux techniques. Both PMA and somatostatin hyperpolarize insulinoma cells by activating ATP-sensitive K + channels. The presence of intracellular GTP is required for the somatostatin effects. PMA- and somatostatin-induced hyperpolarization and channel activity are inhibited by the sulfonylurea glibenclamide. Glibenclamide-sensitive 86 Rb + efflux from insulinoma cells is stimulated by somatostatin in a dose-dependent manner (half maximal effect at 0.7 nM) and abolished by pertussis toxin pretreatment. Mutual roles of a GTP-binding protein, of protein kinase C, and of cAMP in the regulation of ATP-sensitive K + channels are discussed

  14. Theory of analogous force on number sets

    Energy Technology Data Exchange (ETDEWEB)

    Canessa, Enrique [Abdus Salam International Centre for Theoretical Physics, Trieste (Italy)

    2003-08-01

    A general statistical thermodynamic theory that considers given sequences of x-integers to play the role of particles of known type in an isolated elastic system is proposed. By also considering some explicit discrete probability distributions p{sub x} for natural numbers, we claim that they lead to a better understanding of probabilistic laws associated with number theory. Sequences of numbers are treated as the size measure of finite sets. By considering p{sub x} to describe complex phenomena, the theory leads to derive a distinct analogous force f{sub x} on number sets proportional to ({partial_derivative}p{sub x}/{partial_derivative}x){sub T} at an analogous system temperature T. In particular, this yields to an understanding of the uneven distribution of integers of random sets in terms of analogous scale invariance and a screened inverse square force acting on the significant digits. The theory also allows to establish recursion relations to predict sequences of Fibonacci numbers and to give an answer to the interesting theoretical question of the appearance of the Benford's law in Fibonacci numbers. A possible relevance to prime numbers is also analyzed. (author)

  15. Synthesis and evaluation of ligand targeting the somatostatin receptor for drug delivery to tumor cell

    Energy Technology Data Exchange (ETDEWEB)

    Lee, So Young; Hong, Young Don; Jung, Sung Hee; Choi, Sun Ju [Radioisotope Research Division, Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-12-15

    Most of targeted therapies block the action of certain enzymes, proteins, or other molecules involved in the growth and spread of cancer cells to produce its cytotoxic effect. Either small molecule drugs or monoclonal antibodies are mostly used in targeted therapies. Unfortunately, targeted therapy has a certain degree of unwanted side effect like other cytotoxicity inducing chemotherapies. To overcome and to reduce unwanted side effects during a cancer therapy, recently radiopeptide therapies has got the worlds' attraction for the tumor targeting modalities due to its beneficial effect on less side effect compared to cytotoxic chemotherapies. Among radiopeptide therapies, {sup 177}Lu-DOTATATE is a major modality as an effective one invented so far in treating neuroendocrine tumor (NET) and it has been in clinical trials at least one decade. Although it does have rather effective therapeutic effect on NET, it has less effective in rather large solid tumor. There are many ways to improve or increase therapeutic effect of radiopeptide are a finding the potent small molecules to target the tumor site selectively, or a labeling with radioisotope of emitting high energy, or an improving its biological half-life by introducing different moieties to increase lipophilicity. Present study was focus to increase a biological halflife of radio somatostatin which will target the somatostatin receptor by altering the bifunctional chelator (BFCA) by introducing lipophilic moiety to the somatostatin, which would make the labeled peptide stay longer in the tumor site and thus it can intensify the therapeutic effect on tumor cell itself and around tissues.

  16. Molecular imaging of neuroendocrine tumors using 68Ga-labeled peptides (Somatostatin receptor PET/CT)

    International Nuclear Information System (INIS)

    Baum, R.P.; Prasad, V.; Hoersch, D.

    2009-01-01

    Receptor PET/CT using 68 Ga-labeled somatostatin analogues (DOTA-NOC, DOTA-TOC or DOTA-TATE) enables the highly sensitive molecular imaging of neuroendocrine tumors (NETs) based on the expression of somatostatin receptors and even the detection of receptor subtypes. Our experience after more than 3000 studies shows that receptor PET/CT has a significantly higher tumor detection rate than conventional scintigraphy (even in SPECT/CT technique), and that tumor lesions can be very accurately localized. By calculating standardized uptake values (SUV) - which are reproducible and investigator-independent - patients can be selected for peptide receptor radiotherapy and also the course after therapy can be controlled. Receptor-PET/CT is the most sensitive imaging modality for the detection of unknown primary tumors (CUP syndrome), which is especially true for the detection of neuroendocrine tumors of the pancreas and small bowel; whole-body staging (''one stop shop'') as well as restaging and selection of patients for peptide receptor radiotherapy can be performed using a patient-friendly procedure (examination finished within one hour) exposing the patient to less radiation than whole-body CT scanning. The 68 Ge/ 68 Ga generator has proved very reliable over the years - even in a hospital environment. The effective costs for 68 Ga labeled somatostatin analogues might be less than for scintigraphic agents, provided a certain number of studies per year are performed. The development of new tumor-specific peptides as well as of other DOTA- or NOTA-coupled radiopharmaceuticals opens a new avenue into the future: finally, the 68 Ga generator could play a similar important role for PET/CT as did the 99m Tc-Generator for conventional gamma camera imaging over the last decades. (orig.)

  17. Somatostatin receptor 1 and 5 double knockout mice mimic neurochemical changes of Huntington's disease transgenic mice.

    Directory of Open Access Journals (Sweden)

    Padmesh S Rajput

    Full Text Available Selective degeneration of medium spiny neurons and preservation of medium sized aspiny interneurons in striatum has been implicated in excitotoxicity and pathophysiology of Huntington's disease (HD. However, the molecular mechanism for the selective sparing of medium sized aspiny neurons and vulnerability of projection neurons is still elusive. The pathological characteristic of HD is an extensive reduction of the striatal mass, affecting caudate putamen. Somatostatin (SST positive neurons are selectively spared in HD and Quinolinic acid/N-methyl-D-aspartic acid induced excitotoxicity, mimic the model of HD. SST plays neuroprotective role in excitotoxicity and the biological effects of SST are mediated by five somatostatin receptor subtypes (SSTR1-5.To delineate subtype selective biological responses we have here investigated changes in SSTR1 and 5 double knockout mice brain and compared with HD transgenic mouse model (R6/2. Our study revealed significant loss of dopamine and cAMP regulated phosphoprotein of 32 kDa (DARPP-32 and comparable changes in SST, N-methyl-D-aspartic acid receptors subtypes, calbindin and brain nitric oxide synthase expression as well as in key signaling proteins including calpain, phospho-extracellular-signal-regulated kinases1/2, synapsin-IIa, protein kinase C-α and calcineurin in SSTR1/5(-/- and R6/2 mice. Conversely, the expression of somatostatin receptor subtypes, enkephalin and phosphatidylinositol 3-kinases were strain specific. SSTR1/5 appears to be important in regulating NMDARs, DARPP-32 and signaling molecules in similar fashion as seen in HD transgenic mice.This is the first comprehensive description of disease related changes upon ablation of G- protein coupled receptor gene. Our results indicate that SST and SSTRs might play an important role in regulation of neurodegeneration and targeting this pathway can provide a novel insight in understanding the pathophysiology of Huntington's disease.

  18. Somatostatin receptor scintigraphy in sarcoidosis: relation to selected clinical and laboratory markers.

    Science.gov (United States)

    Piotrowski, Wojciech J; Bieńkiewicz, Małgorzata; Frieske, Izabella; Marczak, Jerzy; Antczak, Adam; Górski, Paweł; Kuśmierek, Jacek; Płachcińska, Anna

    2012-01-01

    Discriminating between active and inactive sarcoidosis may be problematic in everyday clinical practice. There are numerous biochemical markers used in the diagnosis and monitoring of sarcoidosis. Somatostatin receptor (SR) scintigraphy with the use of 99mTc-octreotide may be used to estimate disease activity. The aim of the paper was to assess the value of traditional biomarkers (serum angiotensin-converting enzyme [SACE], C-reactive protein, markers of calcium metabolism, bronchoalveolar lavage fluid [BALF] lymphocytes) and a novel biomarker, 8-isoprostane (8-IP) in exhaled breath condensate (EBC), in the assessment of sarcoidosis activity in relation to somatostatin receptor scintigraphy. The study included 32 patients with sarcoidosis. Scintigraphy was performed using somatostatin analogue, 99mTc-HYNIC-TOC; planar and SPECT/CT images were recorded. The study group was divided into a subgroup with positive radiotracer uptake (n = 20) and without a visible uptake (n = 12). 8-IP levels were measured in EBC by an immunoenzymatic assay. RESULTS We observed a significantly higher EBC 8-IP levels in the subgroup with positive uptake compared with those with negative uptake (19.1 ± 19.8 vs. 5.4 ± 3.5 pg/ml, P = 0.02). The levels of SACE and the percentage of BALF lymphocytes were also nonsignificantly elevated. In the group of patients with positive scintigraphy results, a positive correlation was observed between the uptake ratio and SACE (r = 0.44, P = 0.041). The results indicate low value of biochemical markers in the assessment of disease activity. SR scintigraphy may have practical usefulness in the monitoring of sarcoidosis.

  19. The role of somatostatin in GLP-1-induced inhibition of glucagon secretion in mice

    DEFF Research Database (Denmark)

    Ørgaard, Anne; Holst, Jens J

    2017-01-01

    AIMS/HYPOTHESIS: Glucagon-like peptide-1 (GLP-1) receptor agonists are currently used for the treatment of type 2 diabetes. Their main mechanism of action is enhancement of glucose-induced insulin secretion (from increased beta cell glucose sensitivity) and inhibition of glucagon secretion...... on glucagon secretion is heavily debated. Glucagon inhibition is also said to be glucose-dependent, although it is unclear what is meant by this. We hypothesise here that GLP-1 does not inhibit glucagon secretion during hypoglycaemia because the inhibition depends on somatostatin secretion, which in turn...

  20. Technetium-99m as alternative to produce somatostatin-labeled derivatives: comparative biodistribution evaluation with 111In-DTPA-octreotide

    International Nuclear Information System (INIS)

    Melo, Ivani B.; Buchpiguel, Carlos Alberto; Ueda, Laura T.; Araujo, Elaine B. de; Muramoto, Emiko; Barboza, Marycel F. de; Mengatti, Jair; Silva, Constancia P.G. da

    2008-01-01

    Synthetic somatostatin (SST) analogues have been used in the preparation of receptor-specific radiopharmaceuticals for diagnostic and therapy of neuroendocrine (NE) tumors. 111 In-DTPA-Octreotide (OctreoScan®) has found useful for imaging a range of tumors, including NE cancer, carcinoide and lymphoma. Unfortunately, 111 In is a high-cost cyclotron produced radioisotope with gamma emission not so suitable for scintigraphic images and for dosimetry like 99m Tc. This work studied the labeling conditions with 99m Tc and biological distribution in Swiss mice of two SST analogs (HYNIC-Tyr 3 -Octreotide and HYNICTyr 3 - Octreotate) and compared the biodistribution pattern with 111 In-DTPA-Octreotide. 99 mTc-HYNIC-Tyr 3 - Octreotate ( 99m Tc-HYNIC-TATE) and 99m Tc-HYNIC-Tyr 3 -Octreotide ( 99m Tc-HYNIC-OCT) were produced by labeling conditions using tricine and EDDA as coligands. 111 In-DTPA-Octreotide ( 111 In-DTPA-OCT) was produced by labeling DTPA-Octreotide with 111 InCl 3 (Nordion). Radiochemical purity of labeled preparations was determined by ITLC-SG. Biological distribution studies were performed after injection of radiopharmaceuticals on Swiss mice. Labeling procedures resulted on high radiochemical yield for all three preparations and the labeled products presented high in vitro stability. Biological distribution studies evidenced similar general biodistribution of 99m Tc-labeled peptides when compared with indium-labeled peptide with fast blood clearance and elimination by urinary tract. Kidneys uptake of 99 mTc-HYNIC-TATE are similar to 111 In-DTPA-Octreotide, and both are significantly higher than 99 mTc-HYNIC-OCT. All labeled peptides presented similar uptake on liver, but the retention in time at intestines, particularly at large intestine, was more expressive for 111 In-labeled peptide. The %ID of 99m Tc-HYNIC-OCT and 99m Tc-HYNIC-TATE in organs with high density of SST receptors like pancreas and adrenals were significant and similar to obtained for 111

  1. An intrapatient comparison of 99mTc-EDDA/HYNIC-TOC with 111In-DTPA-octreotide for diagnosis of somatostatin receptor-expressing tumors.

    Science.gov (United States)

    Gabriel, Michael; Decristoforo, Clemens; Donnemiller, Eveline; Ulmer, Hanno; Watfah Rychlinski, Christine; Mather, Stephen J; Moncayo, Roy

    2003-05-01

    The aim of this study was to compare the imaging abilities of the recently developed somatostatin analog, (99m)Tc-hydrazinonicotinyl-Tyr(3)-octreotide ((99m)Tc-HYNIC-TOC [(99m)Tc-TOC]), with (111)In-diethylenediaminepentaacetic acid-D-Phe(1)-octreotide ((111)In-OCT [Octreoscan]) in patients undergoing routine somatostatin receptor (SSTR) scintigraphy. Forty-one patients (20 men, 21 women; age range, 29-75 y; mean age, 56.7 y) with either histologically proven or biologically and clinically suspected endocrine tumors were enrolled in the study. Four groups were distinguished: (a) patients being evaluated for the detection and localization of neuroendocrine tumors (n = 6), (b) tumor staging (n = 19), (c) patients being investigated to determine the SSTR status of tumor lesions (n = 11), and (d) patient follow-up studies (n = 5). Each patient received a mean activity of 150 MBq (111)In-OCT and 350-400 MBq (99m)Tc-TOC. Scintigraphy with (99m)Tc-TOC was performed 4 h after injection and scintigraphy with (111)In-OCT was performed 4 and 24 h after injection. SPECT studies of areas of interest were performed 4 h after injection for both tracers as well as at 24 h after injection for (111)In-OCT. The time interval between the studies using each tracer ranged from 2 to 22 d (mean interval, 9.3 d). (111)In-OCT and (99m)Tc-TOC showed an equivalent scan result in 32 patients (78%), 9 cases showed discrepancies (22%), false-negative results with (111)In-OCT were seen in 6 cases (14.6%), whereas (99m)Tc-TOC was false-positive in 2 cases (4.9%). (111)In-OCT was true-negative in both cases. The false-positive findings of the (99m)Tc-TOC studies were caused by nonspecific uptake in the bowel. In 1 case, (99m)Tc-TOC correctly identified a metastasis in the lumbar spine but both scan results were false-positive because of an inflammatory process. In 21 patients with SSTR-expressing tumors, the semiquantitative region-of-interest analysis showed that (99m)Tc-TOC achieved higher tumor

  2. Analog-to-digital conversion

    CERN Document Server

    Pelgrom, Marcel J M

    2010-01-01

    The design of an analog-to-digital converter or digital-to-analog converter is one of the most fascinating tasks in micro-electronics. In a converter the analog world with all its intricacies meets the realm of the formal digital abstraction. Both disciplines must be understood for an optimum conversion solution. In a converter also system challenges meet technology opportunities. Modern systems rely on analog-to-digital converters as an essential part of the complex chain to access the physical world. And processors need the ultimate performance of digital-to-analog converters to present the results of their complex algorithms. The same progress in CMOS technology that enables these VLSI digital systems creates new challenges for analog-to-digital converters: lower signal swings, less power and variability issues. Last but not least, the analog-to-digital converter must follow the cost reduction trend. These changing boundary conditions require micro-electronics engineers to consider their design choices for...

  3. Analog fourier transform channelizer and OFDM receiver

    OpenAIRE

    2007-01-01

    An OFDM receiver having an analog multiplier based I-Q channelizing filter, samples and holds consecutive analog I-Q samples of an I-Q baseband, the I-Q basebands having OFDM sub-channels. A lattice of analog I-Q multipliers and analog I-Q summers concurrently receives the held analog I-Q samples, performs analog I-Q multiplications and analog I-Q additions to concurrently generate a plurality of analog I-Q output signals, representing an N-point discrete Fourier transform of the held analog ...

  4. Molecular modeling of fentanyl analogs

    Directory of Open Access Journals (Sweden)

    LJILJANA DOSEN-MICOVIC

    2004-11-01

    Full Text Available Fentanyl is a highly potent and clinically widely used narcotic analgesic. A large number of its analogs have been synthesized, some of which (sufentanil and alfentanyl are also in clinical use. Theoretical studies, in recent years, afforded a better understanding of the structure-activity relationships of this class of opiates and allowed insight into the molecular mechanism of the interactions of fentanyl analogs with their receptors. An overview of the current computational techniques for modeling fentanyl analogs, their receptors and ligand-receptor interactions is presented in this paper.

  5. Gemini analogs of vitamin D.

    Science.gov (United States)

    Pazos, Gonzalo; Rivadulla, Marcos L; Pérez-García, Xenxo; Gandara, Zoila; Pérez, Manuel

    2014-01-01

    The Gemini analogs are the last significant contribution to the family of vitamin D derivatives in medicine, for the treatment of cancer. The first Gemini analog was characterized by two symmetric side chains at C-20. Following numerous modifications, the most active analog bears a C-23-triple bond, C-26, 27- hexafluoro substituents on one side chain and a terminal trideuteromethylhydroxy group on the other side chain. This progression was possible due to improvements in the synthetic methods for the preparation of these derivatives, which allowed for increasing molecular complexity and complete diastereoselective control at C-20 and the substituted sidechains.

  6. Ultrastructural autoradiographic localization of somatostatin-28 in the rat pituitary gland

    International Nuclear Information System (INIS)

    Morel, G.; Leroux, P.; Pelletier, G.

    1985-01-01

    To identify the anterior pituitary cell type(s) containing somatostatin-28 (SS-28)-binding sites and to study the internalization processes of this peptide by the target cells, autoradiography was performed on rat anterior pituitaries removed at specific intervals (2-60 min) after iv injection of the [ 125 I]iodo-SS-28 agonist [Leu8,D-Trp22,Tyr25]SS-28 into intact, adrenalectomized, or castrated male rats. At the light microscopic level, the silver grains were found in 75% of cells. Concomitant injection of an excess of unlabeled peptide prevented the binding of label, verifying the specificity of binding. No specific labeling could be detected in the adrenocorticotrophs of adrenalectomized rats or gonadotrophs (castration cells) of castrated rats. At the electron microscopic level, three cell types (somatotrophs, thyrotrophs, and mammotrophs) appear to contain radiolabeled SS-28. The time-course study in somatotrophs of intact animals showed that 2 min after injection, most silver grains were associated with the plasma membrane. Five to 15 min after injection, label was found over both the plasma membrane and cytoplasmic organelles, especially the Golgi apparatus, lysosomes, and secretory granules. At the longest time interval (60 min), labeling was mostly associated with the cytoplasmic organelles. These results indicate that SS-28-binding sites are present only in those cell types in which somatostatin is known to regulate secretory functions. The present data also show that a rapid internalization of the radiolabeled peptide occurs

  7. Technetium-99m somatostatin analogues: effect of labelling methods and peptide sequence

    International Nuclear Information System (INIS)

    Decristoforo, C.; Mather, S.J.

    1999-01-01

    In this paper the preclinical evaluation of the somatostatin analogue RC160 labelled with technetium-99m using bifunctional chelators (BFCs) based on the hydrazinonicotinamide (HYNIC) and N 3 S system is described and a comparison made with [Tyr 3 ]-octreotide (TOC). Conjugates of both peptides with HYNIC, and of RC160 with benzoyl-MAG 3 and an N 3 S-adipate derivative were prepared and radiolabelling performed at high specific activities using tricine, tricine/nicotinic acid and ethylenediamine-N,N'-diacetic adic (EDDA) as co-ligands for HYNIC conjugates. All conjugates and 99m Tc-labelled peptides showed preserved binding affinity for the somatostatin receptor (IC50, Kd 99m Tc-RC160 derivatives compared with 99m Tc-EDDA/HYNIC-[Tyr 3 ]-octreotide (0.2%-3.5%ID/g vs 9.7%ID/g) and correlated well with the reduced internalisation rate for RC160 derivatives. Our results show that the selection of the labelling approach as well as the right choice of the peptide structure are crucial for labelling peptides with 99m Tc to achieve complexes with favourable biodistribution. Despite the relatively low tumour uptake compared with 99m Tc-EDDA/HYNIC-[Tyr 3 ]-octreotide, 99m Tc-RC160 could play a role in imaging tumours that do not bind octreotide derivatives. (orig.)

  8. Experimental peptide receptor radionuclide therapy in radioiodine negative somatostatin receptor positive thyroid cancer

    International Nuclear Information System (INIS)

    Nilica, B.; Kroiss, A.; Putzer, D.; Uprimmy, C.; Warwitz, B.; Kendler, D.; Waitz, D.; Virgolini, I.

    2015-01-01

    Full text of publication follows. Purpose: This retrospective analysis evaluated the time to progression (TTP), progression free survival (PFS) and overall survival (OS) in patients with radioiodine negative thyroid cancer who had undergone peptide receptor radionuclide therapy (PRRT) with 177 Lu-DOTA-TATE, 177 Lu-DOTA-LAN, 90 Y-DOTA-TOC or 90 Y-DOTA-LAN after tumor progression. Methods: Data derived from twenty patients with either differentiated (n=15), anaplastic (n=1) or medullary (n=4) somatostatin receptor positive thyroid cancer who had received treatment with PRRT after tumor progression. TTP, PFS and OS were defined according to the clinical trial endpoints suggested by the FDA (Food and Drug Administration). Progressive disease was defined by sonography, FDG-PET, Ga-DOTA-TOC-PET, or CT (RECIST Criteria). Results: In 17 patients the median overall survival time after the first PRRT was 17.3 (range: 0.1 - 109.7) months. Three patients still alive are actually showing stable disease. The median of PFS in 20 Patients (6 with more than one PRRT-cycle or PRRT-substance) has been 10.9 (range: 0.1 - 44.0) months. The median TTP was 15.6 (range 4.4 to 29.2) months. Conclusion: PRRT appears to be useful in patients with somatostatin receptor positive but radioiodine negative thyroid cancer as a complementary palliative cytotoxic therapy. (authors)

  9. Honey Bee Allatostatins Target Galanin/Somatostatin-Like Receptors and Modulate Learning: A Conserved Function?

    Directory of Open Access Journals (Sweden)

    Elodie Urlacher

    Full Text Available Sequencing of the honeybee genome revealed many neuropeptides and putative neuropeptide receptors, yet functional characterization of these peptidic systems is scarce. In this study, we focus on allatostatins, which were first identified as inhibitors of juvenile hormone synthesis, but whose role in the adult honey bee (Apis mellifera brain remains to be determined. We characterize the bee allatostatin system, represented by two families: allatostatin A (Apime-ASTA and its receptor (Apime-ASTA-R; and C-type allatostatins (Apime-ASTC and Apime-ASTCC and their common receptor (Apime-ASTC-R. Apime-ASTA-R and Apime-ASTC-R are the receptors in bees most closely related to vertebrate galanin and somatostatin receptors, respectively. We examine the functional properties of the two honeybee receptors and show that they are transcriptionally expressed in the adult brain, including in brain centers known to be important for learning and memory processes. Thus we investigated the effects of exogenously applied allatostatins on appetitive olfactory learning in the bee. Our results show that allatostatins modulate learning in this insect, and provide important insights into the evolution of somatostatin/allatostatin signaling.

  10. THE EFFECT OF THE SOMATOSTATIN ANALOGUE OCTREOTIDE ON EXPERIMENTAL INTESTINAL OBSTRUCTION IN RATS

    Directory of Open Access Journals (Sweden)

    Paran Haim

    1998-01-01

    Full Text Available Background: Somatostatin has an inhibitory effect on the endocrine and exocrine secretions of the gut. It may have a beneficial effect in the conservative treatment of intestinal obstruction. The aim of the present study is to investigate the effect of octreotide in mechanical intestinal obstruction in rats. Method: Intestinal obstruction was induced in rats by ligation of a segment of the distal ileum. Animals were treated with the somatostatin analogue octreotide (n=16, or saline (n=16. Eight rats were operated but their intestine was not ligated (n=8 serving as sham controls. Forty eight hours after the operation, the animals were operated upon again and blood samples from the femoral vein were tested for electrolytes, urea, glucose, lactic acid, amylase, ph and bicarbonate. Portal vein blood samples were also obtained and tested for lactic acid and amylase. Results: Intestinal obstruction resulted, after 48 hours, in severe dilatation of bowel loops. A significant increase in plasma levels of urea, amylase and lactic acid was observed. Plasma pH decreased. In blood samples from the portal vein, a significant increase in lactic acid was observed, indicating metabolic acidosis, probably secondary to bowel ischemia. Octreotide treatment, resulted in less acidosis, with concomitant lower urea and lactic acid levels in the plasma and especially in the portal vein. Conclusion: Octreotide treatment may have a beneficial effect in the conservative treatment of selected cases of intestinal obstruction.

  11. Analog filters in nanometer CMOS

    CERN Document Server

    Uhrmann, Heimo; Zimmermann, Horst

    2014-01-01

    Starting from the basics of analog filters and the poor transistor characteristics in nanometer CMOS 10 high-performance analog filters developed by the authors in 120 nm and 65 nm CMOS are described extensively. Among them are gm-C filters, current-mode filters, and active filters for system-on-chip realization for Bluetooth, WCDMA, UWB, DVB-H, and LTE applications. For the active filters several operational amplifier designs are described. The book, furthermore, contains a review of the newest state of research on low-voltage low-power analog filters. To cover the topic of the book comprehensively, linearization issues and measurement methods for the characterization of advanced analog filters are introduced in addition. Numerous elaborate illustrations promote an easy comprehension. This book will be of value to engineers and researchers in industry as well as scientists and Ph.D students at universities. The book is also recommendable to graduate students specializing on nanoelectronics, microelectronics ...

  12. Analog elements for transuranic chemistries

    International Nuclear Information System (INIS)

    Weimer, W.C.

    1982-01-01

    The analytical technique for measuring trace concentrations of the analog rare earth elements has been refined for optimal detection. The technique has been used to determine the rare earth concentrations in a series of geological and biological materials, including samples harvested from controlled lysimeter investigations. These studies have demonstrated that any of the trivalent rare earth elements may be used as analog elements for the trivalent transuranics, americium and curium

  13. CMOS Analog IC Design: Fundamentals

    OpenAIRE

    Bruun, Erik

    2018-01-01

    This book is intended for use as the main textbook for an introductory course in CMOS analog integrated circuit design. It is aimed at electronics engineering students who have followed basic courses in mathematics, physics, circuit theory, electronics and signal processing. It takes the students directly from a basic level to a level where they can start working on simple analog IC design projects or continue their studies using more advanced textbooks in the field. A distinct feature of thi...

  14. Analogical proportions: another logical view

    Science.gov (United States)

    Prade, Henri; Richard, Gilles

    This paper investigates the logical formalization of a restricted form of analogical reasoning based on analogical proportions, i.e. statements of the form a is to b as c is to d. Starting from a naive set theoretic interpretation, we highlight the existence of two noticeable companion proportions: one states that a is to b the converse of what c is to d (reverse analogy), while the other called paralogical proportion expresses that what a and b have in common, c and d have it also. We identify the characteristic postulates of the three types of proportions and examine their consequences from an abstract viewpoint. We further study the properties of the set theoretic interpretation and of the Boolean logic interpretation, and we provide another light on the understanding of the role of permutations in the modeling of the three types of proportions. Finally, we address the use of these proportions as a basis for inference in a propositional setting, and relate it to more general schemes of analogical reasoning. The differences between analogy, reverse-analogy, and paralogy is still emphasized in a three-valued setting, which is also briefly presented.

  15. Synthesis, radiochemistry and biological evaluation of a new somatostatin analogue (SDZ 219-387) labelled with technetium-99m

    International Nuclear Information System (INIS)

    Maina, T.; Stolz, B.; Albert, R.; Bruns, C.; Koch, P.; Maecke, H.

    1994-01-01

    A new derivative of octreotide SDZ 219-387 [PnAO-(D)Phe 1 -octreotide] was synthesized, which binds specifically and with high affinity to somatostatin receptors in vitro (pK i =9.79±0.16). This new somatostatin analogue chelates technetium-99m under mild labelling conditions in good yields. The resulting [ 99m Tc]SDZ 219-387 was stable up to 6 h after labelling and could be isolated in a pure radiochemical and chemical form by high-perfomance liquid chromatographic purification. The intravenous administration of purified [ 99m Tc]SDZ 219-387 revealed that the radioligand was rapidly cleared from circulation, and tumour uptake of 0.38% ID/g was observed at 1.5 h post injection. [ 99m Tc]SDZ 219-387 specifically interacted with somatostatin binding sites on the tumour. However, the radioligand is highly lipophilic and excreted mainly through the hepatobiliary system. As a consequence, [ 99m Tc]SDZ 219-387 exhibits increased background activity and therefore is not appropriate for the in vivo visualization of somatostatin receptor-positive tumours and/or their metastases in the abdomen. (orig.)

  16. Immunohistochemical expression of insulin, glucagon, and somatostatin in pancreatic islets of horses with and without insulin resistance.

    Science.gov (United States)

    Newkirk, Kim M; Ehrensing, Gordon; Odoi, Agricola; Boston, Raymond C; Frank, Nicholas

    2018-02-01

    OBJECTIVE To assess insulin, glucagon, and somatostatin expression within pancreatic islets of horses with and without insulin resistance. ANIMALS 10 insulin-resistant horses and 13 insulin-sensitive horses. PROCEDURES For each horse, food was withheld for at least 10 hours before a blood sample was collected for determination of serum insulin concentration. Horses with a serum insulin concentration horses with a serum insulin concentration > 20 μU/mL underwent a frequently sampled IV glucose tolerance test to determine sensitivity to insulin by minimal model analysis. Horses with a sensitivity to insulin horses were euthanized with a barbiturate overdose, and pancreatic specimens were harvested and immunohistochemically stained for determination of insulin, glucagon, and somatostatin expression in pancreatic islets. Islet hormone expression was compared between insulin-resistant and insulin-sensitive horses. RESULTS Cells expressing insulin, glucagon, and somatostatin made up approximately 62%, 12%, and 7%, respectively, of pancreatic islet cells in insulin-resistant horses and 64%, 18%, and 9%, respectively, of pancreatic islet cells in insulin-sensitive horses. Expression of insulin and somatostatin did not differ between insulin-resistant and insulin-sensitive horses, but the median percentage of glucagon-expressing cells in the islets of insulin-resistant horses was significantly less than that in insulin-sensitive horses. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that, in insulin-resistant horses, insulin secretion was not increased but glucagon production might be downregulated as a compensatory response to hyperinsulinemia.

  17. Gastrin (G) cells and somatostatin (D) cells in patients with dyspeptic symptoms: Helicobacter pylori associated and non-associated gastritis

    NARCIS (Netherlands)

    Liu, Y.; Vosmaer, G. D. C.; Tytgat, G. N. J.; Xiao, S.-D.; ten Kate, F. J. W.

    2005-01-01

    Background: Gastrin G cells and somatostatin D cells are important regulators of gastric acid secretion and alterations in their relative numbers may play a key role in gastroduodenal disease. Aim: To investigate the effect of Helicobacter pylori infection on the density of immunoreactive G and D

  18. Central nervous system immunoreactive somatostatin, substance P and met-enkephalin concentrations in experimental hepatic encephalopathy in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Miller, J.L.; Millar, R.P.; Kirsch, R. (Cape Town Univ. (South Africa))

    1982-06-12

    Immunoreactive somatostatin, substance P and met-enkephalin concentrations were measured in various regions of the rat brain 65 hours after portacaval shunt and compared with concentrations in sham-operated animals. No significant difference was detected in any of the three peptides in the regions studied, suggesting that these peptides do not play a role in the pathogenesis of hepatic encephalopathy.

  19. Molecular imaging with 68Ga-SSTR PET/CT and correlation to immunohistochemistry of somatostatin receptors in neuroendocrine tumours

    International Nuclear Information System (INIS)

    Kaemmerer, Daniel; Haugvik, Sven-Petter; Hommann, Merten; Peter, Luisa; Lupp, Amelie; Schulz, Stefan; Saenger, Joerg; Prasad, Vikas; Kulkarni, Harshad; Baum, Richard Paul

    2011-01-01

    Somatostatin receptors (SSTR) are known for an overexpression in gastroenteropancreatic neuroendocrine tumours (GEP-NET). The aim of the present study was to find out if the receptor density predicted by the semi-quantitative parameters generated from the static positron emission tomography (PET/CT) correlated with the in vitro immunohistochemistry using a novel rabbit monoclonal anti-SSTR2A antibody (clone UMB-1) for specific SSTR2A immunohistochemistry and polyclonal antibodies for SSTR1 and 3-5. Overall 14 surgical specimens generated from 34 histologically documented GEP-NET patients were correlated with the preoperative 68 Ga-DOTA-NOC PET/CT. Quantitative assessment of the receptor density was done using the immunoreactive score (IRS) of Remmele and Stegner; the additional 4-point IRS classification for immunohistochemistry and standardized uptake values (SUV max and SUV mean ) were used for PET/CT. The IRS for SSTR2A and SSTR5 correlated highly significant with the SUV max on the PET/CT (p mean (p max on the 68 Ga-DOTA-NOC PET/CT scans is concordant with the affinity profile of 68 Ga-DOTA-NOC to the SSTR subtypes and demonstrates the excellent qualification of somatostatin analogues in the diagnostics of NET. This study correlating somatostatin receptor imaging using 68 Ga-DOTA-NOC PET/CT with immunohistochemically analysed SSTR also underlines the approval of therapy using somatostatin analogues, follow-up imaging as well as radionuclide therapy. (orig.)

  20. Effect of somatostatin on repair of ionizing radiation-induced DNA damage in pituitary adenoma cells GH3

    Czech Academy of Sciences Publication Activity Database

    Řezáčová, M.; Čáp, J.; Vokurková, D.; Lukášová, Emilie; Vávrová, J.; Cerman, J.; Mašín, V.; Mazánková, N.

    2008-01-01

    Roč. 57, č. 2 (2008), s. 225-235 ISSN 0862-8408 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : acromegaly * somatostatin * ionizing radiation Subject RIV: BO - Biophysics Impact factor: 1.653, year: 2008

  1. Long-term effects of cholinergic basal forebrain lesions on neuropeptide Y and somatostatin immunoreactivity in rat neocortex

    NARCIS (Netherlands)

    Gaykema, R.P.A.; Compaan, J.C.; Nyakas, C.; Horvath, E.; Luiten, P.G.M.

    1989-01-01

    The effect of cholinergic basal forebrain lesions on immunoreactivity to somatostatin (SOM-i) and neuropeptide-Y (NPY-i) was investigated in the rat parietal cortex, 16-18 months after multiple bilateral ibotenic acid injections in the nucleus basalis complex. As a result of the lesion, the

  2. Somatostatin receptor gene therapy combined with targeted therapy with radiolabeled octreotide: a new treatment for liver metastases.

    NARCIS (Netherlands)

    A. Mearadji (Amir); W.A.P. Breeman (Wouter); L.J. Hofland (Leo); R.L. Marquet (Richard); J. Jeekel (Hans); E.P. Krenning (Eric); C.H.J. van Eijck (Casper); P.M. van Koetsveld (Peter)

    2002-01-01

    textabstractOBJECTIVE: To evaluate the effect of peptide receptor radionuclide therapy (PRRT) on somatostatin receptor (SSR)-transfected colon carcinoma cells in a rat liver metastases model.SUMMARY BACKGROUND DATA: Previously the authors have shown highly effective therapy with

  3. Evaluation of somatostatin and nucleolin receptors for therapeutic delivery in non-small cell lung cancer stem cells applying the somatostatin-analog DOTATATE and the nucleolin-targeting aptamer AS1411

    DEFF Research Database (Denmark)

    Holmboe, Sif; Hansen, Pernille Lund; Thisgaard, Helge

    2017-01-01

    Cancer stem cells represent the putative tumor-driving subpopulation thought to account for drug resistance, relapse, and metastatic spread of epithelial and other cancer types. Accordingly, cell surface markers for therapeutic delivery to cancer stem cells are subject of intense research. Somato...

  4. Producing and Recognizing Analogical Relations

    Science.gov (United States)

    Lipkens, Regina; Hayes, Steven C

    2009-01-01

    Analogical reasoning is an important component of intelligent behavior, and a key test of any approach to human language and cognition. Only a limited amount of empirical work has been conducted from a behavior analytic point of view, most of that within Relational Frame Theory (RFT), which views analogy as a matter of deriving relations among relations. The present series of four studies expands previous work by exploring the applicability of this model of analogy to topography-based rather than merely selection-based responses and by extending the work into additional relations, including nonsymmetrical ones. In each of the four studies participants pretrained in contextual control over nonarbitrary stimulus relations of sameness and opposition, or of sameness, smaller than, and larger than, learned arbitrary stimulus relations in the presence of these relational cues and derived analogies involving directly trained relations and derived relations of mutual and combinatorial entailment, measured using a variety of productive and selection-based measures. In Experiment 1 participants successfully recognized analogies among stimulus networks containing same and opposite relations; in Experiment 2 analogy was successfully used to extend derived relations to pairs of novel stimuli; in Experiment 3 the procedure used in Experiment 1 was extended to nonsymmetrical comparative relations; in Experiment 4 the procedure used in Experiment 2 was extended to nonsymmetrical comparative relations. Although not every participant showed the effects predicted, overall the procedures occasioned relational responses consistent with an RFT account that have not yet been demonstrated in a behavior-analytic laboratory setting, including productive responding on the basis of analogies. PMID:19230515

  5. Are radiogallium-labelled DOTA-conjugated somatostatin analogues superior to those labelled with other radiometals?

    Energy Technology Data Exchange (ETDEWEB)

    Antunes, P.; Ginj, M.; Zhang, H.; Maecke, H. [University Hospital Basel, Division of Radiological Chemistry, Basel (Switzerland); Waser, B.; Reubi, J.C. [University of Bern, Institute of Pathology, Bern (Switzerland); Baum, R.P. [Zentralklinik Bad Berka, Department of Nuclear Medicine/PETCT-Center, Bad Berka (Germany)

    2007-07-15

    Gallium-68 is a metallic positron emitter with a half-life of 68 min that is ideal for the in vivo use of small molecules, such as [{sup 68}Ga-DOTA,Tyr{sup 3}]octreotide, in the diagnostic imaging of somatostatin receptor-positive tumours. In preclinical studies it has shown a striking superiority over its {sup 111}In-labelled congener. The purpose of this study was to evaluate whether third-generation somatostatin-based, radiogallium-labelled peptides show the same superiority. Peptides were synthesised on solid phase. The receptor affinity was determined by in vitro receptor autoradiography. The internalisation rate was studied in AR4-2J and hsst-HEK-transfected cell lines. The pharmacokinetics was studied in a rat xenograft tumour model, AR4-2J. All peptides showed high affinities on hsst2, with the highest affinity for the Ga{sup III}-complexed peptides. On hsst3 the situation was reversed, with a trend towards lower affinity of the Ga{sup III} peptides. A significantly increased internalisation rate was found in sst2-expressing cells for all {sup 67}Ga-labelled peptides. Internalisation into HEK-sst3 was usually faster for the {sup 111}In-labelled peptides. No internalisation was found into sst5. Biodistribution studies employing [{sup 67}Ga-DOTA,1-Nal{sup 3}]octreotide in comparison to [{sup 111}In-DOTA,1-Nal{sup 3}]octreotide and [{sup 67}Ga-DOTA,Tyr{sup 3}]octreotide showed a significantly higher and receptor-mediated uptake of the two{sup 67}Ga-labelled peptides in the tumour and somatostatin receptor-positive tissues. A patient study illustrated the potential advantage of a broad receptor subtype profile radiopeptide over a high-affinity sst2-selective radiopeptide. This study demonstrates that {sup 67/68}Ga-DOTA-octapeptides show distinctly better preclinical, pharmacological performances than the {sup 111}In-labelled peptides, especially on sst2-expressing cells and the corresponding animal models. They may be excellent candidates for further

  6. Are radiogallium-labelled DOTA-conjugated somatostatin analogues superior to those labelled with other radiometals?

    International Nuclear Information System (INIS)

    Antunes, P.; Ginj, M.; Zhang, H.; Maecke, H.; Waser, B.; Reubi, J.C.; Baum, R.P.

    2007-01-01

    Gallium-68 is a metallic positron emitter with a half-life of 68 min that is ideal for the in vivo use of small molecules, such as [ 68 Ga-DOTA,Tyr 3 ]octreotide, in the diagnostic imaging of somatostatin receptor-positive tumours. In preclinical studies it has shown a striking superiority over its 111 In-labelled congener. The purpose of this study was to evaluate whether third-generation somatostatin-based, radiogallium-labelled peptides show the same superiority. Peptides were synthesised on solid phase. The receptor affinity was determined by in vitro receptor autoradiography. The internalisation rate was studied in AR4-2J and hsst-HEK-transfected cell lines. The pharmacokinetics was studied in a rat xenograft tumour model, AR4-2J. All peptides showed high affinities on hsst2, with the highest affinity for the Ga III -complexed peptides. On hsst3 the situation was reversed, with a trend towards lower affinity of the Ga III peptides. A significantly increased internalisation rate was found in sst2-expressing cells for all 67 Ga-labelled peptides. Internalisation into HEK-sst3 was usually faster for the 111 In-labelled peptides. No internalisation was found into sst5. Biodistribution studies employing [ 67 Ga-DOTA,1-Nal 3 ]octreotide in comparison to [ 111 In-DOTA,1-Nal 3 ]octreotide and [ 67 Ga-DOTA,Tyr 3 ]octreotide showed a significantly higher and receptor-mediated uptake of the two 67 Ga-labelled peptides in the tumour and somatostatin receptor-positive tissues. A patient study illustrated the potential advantage of a broad receptor subtype profile radiopeptide over a high-affinity sst2-selective radiopeptide. This study demonstrates that 67/68 Ga-DOTA-octapeptides show distinctly better preclinical, pharmacological performances than the 111 In-labelled peptides, especially on sst2-expressing cells and the corresponding animal models. They may be excellent candidates for further development for clinical studies. (orig.)

  7. Fast multichannel analog storage system

    International Nuclear Information System (INIS)

    Freytag, D.R.

    1982-11-01

    A Multichannel Analog Storage System based on a commercial 32-channel parallel in/serial out (PISO) analog shift register is described. The basic unit is a single width CAMAC module containing 512 analog cells and the associated logic for data storage and subsequent readout. At sampling rates of up to 30 MHz the signals are strobed directly into the PISO. At higher rates signals are strobed into a fast presampling stage and subsequently transferred in block form into an array of PISO's. Sampling rates of 300 MHz have been achieved with the present device and 1000 MHz are possible with improved signal drivers. The system is well suited for simultaneous handling of many signal channels with moderate numbers of samples in each channel. RMS noise over full scale signal has been measured as 1:3000 (approx. = 11 bit). However, nonlinearities in the response and differences in sensitivity of the analog cells require an elaborate calibration system in order to realize 11 bit accuracy for the analog information

  8. SSERVI Analog Regolith Simulant Testbed Facility

    Science.gov (United States)

    Minafra, Joseph; Schmidt, Gregory; Bailey, Brad; Gibbs, Kristina

    2016-10-01

    The Solar System Exploration Research Virtual Institute (SSERVI) at NASA's Ames Research Center in California's Silicon Valley was founded in 2013 to act as a virtual institute that provides interdisciplinary research centered on the goals of its supporting directorates: NASA Science Mission Directorate (SMD) and the Human Exploration & Operations Mission Directorate (HEOMD).Primary research goals of the Institute revolve around the integration of science and exploration to gain knowledge required for the future of human space exploration beyond low Earth orbit. SSERVI intends to leverage existing JSC1A regolith simulant resources into the creation of a regolith simulant testbed facility. The purpose of this testbed concept is to provide the planetary exploration community with a readily available capability to test hardware and conduct research in a large simulant environment.SSERVI's goals include supporting planetary researchers within NASA, other government agencies; private sector and hardware developers; competitors in focused prize design competitions; and academic sector researchers.SSERVI provides opportunities for research scientists and engineers to study the effects of regolith analog testbed research in the planetary exploration field. This capability is essential to help to understand the basic effects of continued long-term exposure to a simulated analog test environment.The current facility houses approximately eight tons of JSC-1A lunar regolith simulant in a test bin consisting of a 4 meter by 4 meter area, including dust mitigation and safety oversight.Facility hardware and environment testing scenarios could include, Lunar surface mobility, Dust exposure and mitigation, Regolith handling and excavation, Solar-like illumination, Lunar surface compaction profile, Lofted dust, Mechanical properties of lunar regolith, Surface features (i.e. grades and rocks)Numerous benefits vary from easy access to a controlled analog regolith simulant testbed, and

  9. Somatostatin receptors

    DEFF Research Database (Denmark)

    Møller, Lars Neisig; Stidsen, Carsten Enggaard; Hartmann, Bolette

    2003-01-01

    functional units, receptors co-operate. The total receptor apparatus of individual cell types is composed of different-ligand receptors (e.g. SRIF and non-SRIF receptors) and co-expressed receptor subtypes (e.g. sst(2) and sst(5) receptors) in characteristic proportions. In other words, levels of individual......-peptides, receptor agonists and antagonists. Relatively long half lives, as compared to those of the endogenous ligands, have been paramount from the outset. Motivated by theoretical puzzles or the shortcomings of present-day diagnostics and therapy, investigators have also aimed to produce subtype...

  10. Human adipose tissue-derived mesenchymal stem cells differentiate into insulin, somatostatin, and glucagon expressing cells

    International Nuclear Information System (INIS)

    Timper, Katharina; Seboek, Dalma; Eberhardt, Michael; Linscheid, Philippe; Christ-Crain, Mirjam; Keller, Ulrich; Mueller, Beat; Zulewski, Henryk

    2006-01-01

    Mesenchymal stem cells (MSC) from mouse bone marrow were shown to adopt a pancreatic endocrine phenotype in vitro and to reverse diabetes in an animal model. MSC from human bone marrow and adipose tissue represent very similar cell populations with comparable phenotypes. Adipose tissue is abundant and easily accessible and could thus also harbor cells with the potential to differentiate in insulin producing cells. We isolated human adipose tissue-derived MSC from four healthy donors. During the proliferation period, the cells expressed the stem cell markers nestin, ABCG2, SCF, Thy-1 as well as the pancreatic endocrine transcription factor Isl-1. The cells were induced to differentiate into a pancreatic endocrine phenotype by defined culture conditions within 3 days. Using quantitative PCR a down-regulation of ABCG2 and up-regulation of pancreatic developmental transcription factors Isl-1, Ipf-1, and Ngn3 were observed together with induction of the islet hormones insulin, glucagon, and somatostatin

  11. Analog electronics for radiation detection

    CERN Document Server

    2016-01-01

    Analog Electronics for Radiation Detection showcases the latest advances in readout electronics for particle, or radiation, detectors. Featuring chapters written by international experts in their respective fields, this authoritative text: Defines the main design parameters of front-end circuitry developed in microelectronics technologies Explains the basis for the use of complementary metal oxide semiconductor (CMOS) image sensors for the detection of charged particles and other non-consumer applications Delivers an in-depth review of analog-to-digital converters (ADCs), evaluating the pros and cons of ADCs integrated at the pixel, column, and per-chip levels Describes incremental sigma delta ADCs, time-to-digital converter (TDC) architectures, and digital pulse-processing techniques complementary to analog processing Examines the fundamental parameters and front-end types associated with silicon photomultipliers used for single visible-light photon detection Discusses pixel sensors ...

  12. Natural analogs for Yucca Mountain

    International Nuclear Information System (INIS)

    Murphy, W.M.

    1995-01-01

    High-level radioactive waste in the US, spent fuels from commercial reactors and nuclear materials generated by defense activities, will remain potentially hazardous for thousands of years. Demonstrable long-term stability of certain geologic and geochemical systems motivates and sustains the concept that high-level waste can be safely isolated in geologic repositories for requisite periods of time. Each geologic repository is unique in its properties and performance with reguard to isolation of nuclear wastes. Studies of processes analogous to waste-form alteration and radioelement transport in environments analogous to Yucca Mountain are being conducted at two sites, described in this article to illustrate uses of natural analog data: the Nopal I uranium deposit in the Sierra Pena Blanca, Mexico, and the Akrotiri archaeological site on the island of Santorini, Greece

  13. Synthetic Analogs of Phospholipid Metabolites as Antimalarials.

    Science.gov (United States)

    1979-07-01

    phosphatidic acid analogs containing ether and phosphonate groups; completely non- hydrolyzable lecithin analogs containing phosphinate and ether groups...substance is a completely non- hydrolyzable analog of lecithin containing ether and phosphonate moieties instead of the normally labile carboxylic and...and also ant-i-phospholipase C (clostridial enzyme) activity. This substance Is a completely non- hydrolyzable analog of lecithin containing ether

  14. Novel, potent, and radio-iodinatable somatostatin receptor 1 (sst1) selective analogues.

    Science.gov (United States)

    Erchegyi, Judit; Cescato, Renzo; Grace, Christy Rani R; Waser, Beatrice; Piccand, Véronique; Hoyer, Daniel; Riek, Roland; Rivier, Jean E; Reubi, Jean Claude

    2009-05-14

    The proposed sst(1) pharmacophore (J. Med. Chem. 2005, 48, 523-533) derived from the NMR structures of a family of mono- and dicyclic undecamers was used to design octa-, hepta-, and hexamers with high affinity and selectivity for the somatostatin sst(1) receptor. These compounds were tested for their in vitro binding properties to all five somatostatin (SRIF) receptors using receptor autoradiography; those with high SRIF receptor subtype 1 (sst(1)) affinity and selectivity were shown to be agonists when tested functionally in a luciferase reporter gene assay. Des-AA(1,4-6,10,12,13)-[DTyr(2),DAgl(NMe,2naphthoyl)(8),IAmp(9)]-SRIF-Thr-NH(2) (25) was radio-iodinated ((125)I-25) and specifically labeled sst(1)-expressing cells and tissues. 3D NMR structures were calculated for des-AA(1,4-6,10,12,13)-[DPhe(2),DTrp(8),IAmp(9)]-SRIF-Thr-NH(2) (16), des-AA(1,2,4-6,10,12,13)-[DAgl(NMe,2naphthoyl)(8),IAmp(9)]-SRIF-Thr-NH(2) (23), and des-AA(1,2,4-6,10,12,13)-[DAgl(NMe,2naphthoyl)(8),IAmp(9),Tyr(11)]-SRIF-NH(2) (27) in DMSO. Though the analogues have the sst(1) pharmacophore residues at the previously determined distances from each other, the positioning of the aromatic residues in 16, 23, and 27 is different from that described earlier, suggesting an induced fit mechanism for sst(1) binding of these novel, less constrained sst(1)-selective family members.

  15. Altered Expression of Somatostatin Receptors in Pancreatic Islets from NOD Mice Cultured at Different Glucose Concentrations In Vitro and in Islets Transplanted to Diabetic NOD Mice In Vivo

    Directory of Open Access Journals (Sweden)

    Eva Ludvigsen

    2011-01-01

    Full Text Available Somatostatin acts via five receptors (sst1-5. We investigated if the changes in pancreatic islet sst expression in diabetic NOD mice compared to normoglycemic mice are a consequence of hyperglycemia or the ongoing immune reaction in the pancreas. Pancreatic islets were isolated from NOD mice precultured for 5 days and further cultured for 3 days at high or low glucose before examined. Islets were also isolated from NOD mice and transplanted to normal or diabetic mice in a number not sufficient to cure hyperglycemia. After three days, the transplants were removed and stained for sst1-5 and islet hormones. Overall, changes in sst islet cell expression were more common in islets cultured in high glucose concentration in vitro as compared to the islet transplantation in vivo to diabetic mice. The beta and PP cells exhibited more frequent changes in sst expression, while the alpha and delta cells were relatively unaffected by the high glucose condition. Our findings suggest that the glucose level may alter sst expressed in islets cells; however, immune mechanisms may counteract such changes in islet sst expression.

  16. Effects of a somatostatin derivative (SMS 201-995) on postprandial hyperglycemia in insulin-dependent diabetics studied by means of a closed-loop device.

    Science.gov (United States)

    Nosari, I; Lepore, G; Querci, F; Maglio, M L; Sileo, F; Pagani, G

    1989-06-01

    We studied the effects of a premeal sc injection of an analog of somatostatin (SMS 201-995, Sandoz) on the postprandial glycemic excursions, insulin requirement and hormone profiles (GH, glucagon and C-peptide) in 8 IDDM patients (diabetes duration 14.0 +/- 6.5 yr, daily insulin requirement 36 +/- 6.4 U) maintained normoglycemic by connecting them to a closed-loop insulin infusion system (Betalike, Genoa). The morning of the test the patients were connected to the Betalike and their glucose levels stabilized for at least 4 h. At 13:00 h the study was begun with a sc injection of 50 micrograms of SMS 201-995 or placebo (randomly) and a standardized mixed meal (800 Kcal) was given. Blood samples were obtained 0, 15, 30, 60, 120 and 180 min after the injection. Each patient was tested both with SMS 201-995 and placebo. Postmeal glycemic peaks were decreased after SMS 201-995 (119.6 +/- 5.4 mg/dl vs 149.1 +/- 4.2; p less than 0.05) as well as insulin requirements (3.2 +/- 0.8 U vs 13.3 +/- 1.9; p less than 0.01) for the 180 min postprandial period. Similarly, glucagon level was reduced 30 min postprandially (24 +/- 6 pg/ml vs 59 +/- 24; p less than 0.05) and so GH level only 180 min after lunch (p less than 0.05). The premeal injection of SMS decreases postprandial glycemic excursions and the corresponding insulin requirement. The action of SMS 201-995 may be mainly mediated by the suppression of postprandial glucagon peak.

  17. Multichannel analog temperature sensing system

    International Nuclear Information System (INIS)

    Gribble, R.

    1985-08-01

    A multichannel system that protects the numerous and costly water-cooled magnet coils on the translation section of the FRX-C/T magnetic fusion experiment is described. The system comprises a thermistor for each coil, a constant current circuit for each thermistor, and a multichannel analog-to-digital converter interfaced to the computer

  18. 49205 ANALOGE OG DIGITALE FILTRE

    DEFF Research Database (Denmark)

    Gaunholt, Hans

    1997-01-01

    Theese lecture notes treats the fundamental theory and the most commonly used design methods for passive- active and digital filters with special emphasis on microelectronic realizations. The lecture notes covers 75% of the material taught in the course 49205 Analog and Digital Filters...

  19. Drawing Analogies to Deepen Learning

    Science.gov (United States)

    Fava, Michelle

    2017-01-01

    This article offers examples of how drawing can facilitate thinking skills that promote analogical reasoning to enable deeper learning. The instructional design applies cognitive principles, briefly described here. The workshops were developed iteratively, through feedback from student and teacher participants. Elements of the UK National…

  20. Glycine-extended gastrin enhances somatostatin release from cultured rabbit fundic D-cells [v1; ref status: indexed, http://f1000r.es/8n

    Directory of Open Access Journals (Sweden)

    Ian LP Beales

    2013-02-01

    Full Text Available The role of the peptide hormone gastrin in stimulating gastric acid secretion is well established. Mature amidated gastrin is processed from larger peptide precursor forms. Increasingly these processing intermediates, such as glycine-extended gastrin (G-Gly and progastrin, have been shown to have biological activities of their own, often separate and complementary to gastrin. Although G-Gly is synthesized and secreted by gastric antral G-cells, the physiological functions of this putative mediator are unclear. Gastrin and cholecystokinin (CCK stimulate the secretion of somatostatin from gastric D-cells as part of the feedback control of gastric acid. In this study the effect of G-Gly and gastrin on the release of somatostatin from rabbit fundic D-cells was examined. D-cells were obtained by collagenase-EDTA digestion and elutriation and cultured for 48 hours. With a 2 hour exposure to the peptides, gastrin but not G-Gly stimulated somatostatin release. Treatment of D-cells for 24 hours with gastrin or G-Gly individually, significantly enhanced subsequent basal as well as CCK- and GLP-1-stimulated somatostatin release. Twenty four hours exposure to gastrin combined with G-Gly synergistically enhanced basal and agonist-stimulated somatostatin release and cellular somatostatin content. Gastrin and G-Gly may be important in the longer term regulation of D-cell function.

  1. Somatostatin-immunoreactive senile plaque-like structures in the frontal cortex and nucleus accumbens of aged tree shrews and Japanese macaques.

    Science.gov (United States)

    Yamashita, Akiko; Fuchs, Eberhard; Taira, Masato; Yamamoto, Takamitsu; Hayashi, Motoharu

    2012-06-01

    Previously, we demonstrated decreased expression of somatostatin mRNA in aged macaque brain, particularly in the prefrontal cortex. To investigate whether or not this age-dependent decrease in mRNA is related to morphological changes, we analyzed somatostatin cells in the cerebra of aged Japanese macaques and compared them with those in rats and tree shrews, the latter of which are closely related to primates. Brains of aged macaques, tree shrews, and rats were investigated by immunohistochemistry with special emphasis on somatostatin. We observed degenerating somatostatin-immunoreactive cells in the cortices of aged macaques and tree shrews. Somatostatin-immunoreactive senile plaque-like structures were found in areas 6 and 8 and in the nucleus accumbens of macaques, as well as in the nucleus accumbens and the cortex of aged tree shrews, where amyloid accumulations were observed. Somatostatin degenerations may be related to amyloid accumulations and may play roles in impairments of cognitive functions during aging. © 2012 John Wiley & Sons A/S.

  2. Bayesian analogy with relational transformations.

    Science.gov (United States)

    Lu, Hongjing; Chen, Dawn; Holyoak, Keith J

    2012-07-01

    How can humans acquire relational representations that enable analogical inference and other forms of high-level reasoning? Using comparative relations as a model domain, we explore the possibility that bottom-up learning mechanisms applied to objects coded as feature vectors can yield representations of relations sufficient to solve analogy problems. We introduce Bayesian analogy with relational transformations (BART) and apply the model to the task of learning first-order comparative relations (e.g., larger, smaller, fiercer, meeker) from a set of animal pairs. Inputs are coded by vectors of continuous-valued features, based either on human magnitude ratings, normed feature ratings (De Deyne et al., 2008), or outputs of the topics model (Griffiths, Steyvers, & Tenenbaum, 2007). Bootstrapping from empirical priors, the model is able to induce first-order relations represented as probabilistic weight distributions, even when given positive examples only. These learned representations allow classification of novel instantiations of the relations and yield a symbolic distance effect of the sort obtained with both humans and other primates. BART then transforms its learned weight distributions by importance-guided mapping, thereby placing distinct dimensions into correspondence. These transformed representations allow BART to reliably solve 4-term analogies (e.g., larger:smaller::fiercer:meeker), a type of reasoning that is arguably specific to humans. Our results provide a proof-of-concept that structured analogies can be solved with representations induced from unstructured feature vectors by mechanisms that operate in a largely bottom-up fashion. We discuss potential implications for algorithmic and neural models of relational thinking, as well as for the evolution of abstract thought. Copyright 2012 APA, all rights reserved.

  3. Crows spontaneously exhibit analogical reasoning.

    Science.gov (United States)

    Smirnova, Anna; Zorina, Zoya; Obozova, Tanya; Wasserman, Edward

    2015-01-19

    Analogical reasoning is vital to advanced cognition and behavioral adaptation. Many theorists deem analogical thinking to be uniquely human and to be foundational to categorization, creative problem solving, and scientific discovery. Comparative psychologists have long been interested in the species generality of analogical reasoning, but they initially found it difficult to obtain empirical support for such thinking in nonhuman animals (for pioneering efforts, see [2, 3]). Researchers have since mustered considerable evidence and argument that relational matching-to-sample (RMTS) effectively captures the essence of analogy, in which the relevant logical arguments are presented visually. In RMTS, choice of test pair BB would be correct if the sample pair were AA, whereas choice of test pair EF would be correct if the sample pair were CD. Critically, no items in the correct test pair physically match items in the sample pair, thus demanding that only relational sameness or differentness is available to support accurate choice responding. Initial evidence suggested that only humans and apes can successfully learn RMTS with pairs of sample and test items; however, monkeys have subsequently done so. Here, we report that crows too exhibit relational matching behavior. Even more importantly, crows spontaneously display relational responding without ever having been trained on RMTS; they had only been trained on identity matching-to-sample (IMTS). Such robust and uninstructed relational matching behavior represents the most convincing evidence yet of analogical reasoning in a nonprimate species, as apes alone have spontaneously exhibited RMTS behavior after only IMTS training. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Privacy Act

    Science.gov (United States)

    Learn about the Privacy Act of 1974, the Electronic Government Act of 2002, the Federal Information Security Management Act, and other information about the Environmental Protection Agency maintains its records.

  5. Immunohistochemical Detection and Localization of Somatostatin Receptor Subtypes in Prostate Tissue from Patients with Bladder Outlet Obstruction

    Directory of Open Access Journals (Sweden)

    Rodolfo Montironi

    2008-01-01

    Full Text Available Background and Aim of the Study: Scant information on the cellular distribution of the five somatostatin receptor (SSTR subtypes in the normal prostate and in neoplasms of the prostate has been reported in very few studies in which techniques, such as in situ hybridization histochemistry, autoradiography, and more recently immunohistochemistry, have been applied. The aim of the study was to examine immunohistochemically the distribution and localization of these 5 subtypes in the various tissue components in normal prostate.

  6. Somatostatin-based Radiopeptide Therapy with [177Lu-DOTA]-TOC versus [90Y-DOTA]-TOC in Neuroendocrine Tumors

    OpenAIRE

    Romer A Seiler D Marincek N Brunner P Koller MT Ng QK Maecke HR Muller-Brand J Rochlitz C B

    2014-01-01

    PURPOSE: Somatostatin based radiopeptide treatment is generally performed using the ß emitting radionuclides (90)Y or (177)Lu. The present study aimed at comparing benefits and harms of both therapeutic approaches. METHODS: In a comparative cohort study patients with advanced neuroendocrine tumours underwent repeated cycles of [(90)Y DOTA] TOC or [(177)Lu DOTA] TOC until progression of disease or permanent adverse events. Multivariable Cox regression and competing risks regression were emplo...

  7. Analog circuit design art, science and personalities

    CERN Document Server

    Williams, Jim

    1991-01-01

    This book is far more than just another tutorial or reference guide - it's a tour through the world of analog design, combining theory and applications with the philosophies behind the design process. Readers will learn how leading analog circuit designers approach problems and how they think about solutions to those problems. They'll also learn about the `analog way' - a broad, flexible method of thinking about analog design tasks.A comprehensive and useful guide to analog theory and applications. Covers visualizing the operation of analog circuits. Looks at how to rap

  8. Quantum Dot Immunocytochemical Localization of Somatostatin in Somatostatinoma by Widefield Epifluorescence, Super-resolution Light, and Immunoelectron Microscopy

    Science.gov (United States)

    Lai, Ken; Wu, Xiaojuan; Yong, Jim L. C.; Lee, C. Soon

    2012-01-01

    Quantum dot nanocrystal probes (QDs) have been used for detection of somatostatin hormone in secretory granules of somatostatinoma tumor cells by immunofluorescence light microscopy, super-resolution light microscopy, and immunoelectron microscopy. Immunostaining for all modalities was done using sections taken from an epoxy resin-embedded tissue specimen and a similar labeling protocol. This approach allowed assessment of labeling at light microscopy level before examination at super-resolution and electron microscopy level and was a significant aid in interpretation. Etching of ultrathin sections with saturated sodium metaperiodate was a critical step presumably able to retrieve some tissue antigenicity masked by processing in epoxy resin. Immunofluorescence microscopy of QD-immunolabeled sections showed somatostatin hormone localization in cytoplasmic granules. Some variable staining of tumor gland-like structures appeared related to granule maturity and dispersal of granule contents within the tumor cell cytoplasm. Super-resolution light microscopy demonstrated localization of somatostatin within individual secretory granules to be heterogeneous, and this staining pattern was confirmed by immunoelectron microscopy. PMID:22899862

  9. Quantum dot immunocytochemical localization of somatostatin in somatostatinoma by Widefield Epifluorescence, super-resolution light, and immunoelectron microscopy.

    Science.gov (United States)

    Killingsworth, Murray C; Lai, Ken; Wu, Xiaojuan; Yong, Jim L C; Lee, C Soon

    2012-11-01

    Quantum dot nanocrystal probes (QDs) have been used for detection of somatostatin hormone in secretory granules of somatostatinoma tumor cells by immunofluorescence light microscopy, super-resolution light microscopy, and immunoelectron microscopy. Immunostaining for all modalities was done using sections taken from an epoxy resin-embedded tissue specimen and a similar labeling protocol. This approach allowed assessment of labeling at light microscopy level before examination at super-resolution and electron microscopy level and was a significant aid in interpretation. Etching of ultrathin sections with saturated sodium metaperiodate was a critical step presumably able to retrieve some tissue antigenicity masked by processing in epoxy resin. Immunofluorescence microscopy of QD-immunolabeled sections showed somatostatin hormone localization in cytoplasmic granules. Some variable staining of tumor gland-like structures appeared related to granule maturity and dispersal of granule contents within the tumor cell cytoplasm. Super-resolution light microscopy demonstrated localization of somatostatin within individual secretory granules to be heterogeneous, and this staining pattern was confirmed by immunoelectron microscopy.

  10. Diet-Induced Growth Is Regulated via Acquired Leptin Resistance and Engages a Pomc-Somatostatin-Growth Hormone Circuit

    Directory of Open Access Journals (Sweden)

    Heiko Löhr

    2018-05-01

    Full Text Available Summary: Anorexigenic pro-opiomelanocortin (Pomc/alpha-melanocyte stimulating hormone (αMSH neurons of the hypothalamic melanocortin system function as key regulators of energy homeostasis, also controlling somatic growth across different species. However, the mechanisms of melanocortin-dependent growth control still remain ill-defined. Here, we reveal a thus-far-unrecognized structural and functional connection between Pomc neurons and the somatotropic hypothalamo-pituitary axis. Excessive feeding of larval zebrafish causes leptin resistance and reduced levels of the hypothalamic satiety mediator pomca. In turn, this leads to reduced activation of hypophysiotropic somatostatin (Sst-neurons that express the melanocortin receptor Mc4r, elevated growth hormone (GH expression in the pituitary, and enhanced somatic growth. Mc4r expression and αMSH responsiveness are conserved in Sst-expressing hypothalamic neurons of mice. Thus, acquired leptin resistance and attenuation of pomca transcription in response to excessive caloric intake may represent an ancient mechanism to promote somatic growth when food resources are plentiful. : The melanocortin system controls energy homeostasis and somatic growth, but the underlying mechanisms are elusive. Löhr et al. identify a functional neural circuit in which Pomc neurons stimulate hypothalamic somatostatin neurons, thereby inhibiting hypophyseal growth hormone production. Excessive feeding and acquired leptin resistance attenuate this pathway, allowing faster somatic growth when food resources are rich. Keywords: Pomc neuron, somatostatin neuron, somatic growth, growth hormone, melanocortin system, high-fat diet, obesity, leptin resistance, zebrafish, mouse

  11. Analog-to-digital conversion

    CERN Document Server

    Pelgrom, Marcel

    2017-01-01

    This textbook is appropriate for use in graduate-level curricula in analog-to-digital conversion, as well as for practicing engineers in need of a state-of-the-art reference on data converters. It discusses various analog-to-digital conversion principles, including sampling, quantization, reference generation, nyquist architectures and sigma-delta modulation. This book presents an overview of the state of the art in this field and focuses on issues of optimizing accuracy and speed, while reducing the power level. This new, third edition emphasizes novel calibration concepts, the specific requirements of new systems, the consequences of 22-nm technology and the need for a more statistical approach to accuracy. Pedagogical enhancements to this edition include additional, new exercises, solved examples to introduce all key, new concepts and warnings, remarks and hints, from a practitioner’s perspective, wherever appropriate. Considerable background information and practical tips, from designing a PCB, to lay-o...

  12. Analogies between antiferromagnets and antiferroelectrics

    International Nuclear Information System (INIS)

    Enz, C.P.; Matthias, B.T.

    1980-01-01

    Ferro- and antiferromagnetism in the Laves phase TiBesub(2-x) Cusub(x) occurs for 0.1 4 H 2 PO 4 and its solid solutions with TlH 2 PO 4 and with the ferroelectric KH 2 PO 4 are discussed as function of deuteration and of pressure. Another analogy as function of pressure is established with the antiferroelectric perovskite PbZrO 3 . (author)

  13. Novel phosphanucleoside analogs of dideoxynucleosides

    Czech Academy of Sciences Publication Activity Database

    Páv, Ondřej; Buděšínský, Miloš; Rosenberg, Ivan

    2017-01-01

    Roč. 73, č. 34 (2017), s. 5220-5228 ISSN 0040-4020 R&D Projects: GA ČR(CZ) GA17-12703S; GA ČR GA13-26526S; GA MZd NV15-31604A Institutional support: RVO:61388963 Keywords : phosphanucleoside * nucleoside analog * ring-closing metathesis * stereoselective hydroboration * chiral resolution Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 2.651, year: 2016

  14. [Construction and immunogenicity of recombinant porcine parvovirus-like particles with somatostatin].

    Science.gov (United States)

    Zhang, Xuehua; Zheng, Qisheng; Chen, Jin; Xue, Gang; Hou, Hongyan; Hou, Jibo

    2010-08-01

    In order to obtain a virus-like particle vaccine both for porcine parvovirus (PPV) prevention and growth-promotion, VP2 gene of PPV NJ-a strain was amplified with PCR, and four copies of synthetic somatostatin gene were fused to the N-terminal of VP2 gene. The fused gene was cloned into pFast-HT A to construct the recombinant plasmid pFast-SS4-VP2, then the pFast-SS4-VP2 was transformed into DH10Bac competent cells and recombined with shuttle vector Bacmid, followed by identification with blue-white screening and PCR analysis for three cycles, and the positive recombinant was named as rBacmid-SS4-VP2. The positive Sf-9 cells were transfected with rBacmid-SS4-VP2 by Lipofectamine to produce recombinant baculovirus. When the cytopathic effect (CPE) was obvious, the transfected Sf-9 cell was harvested, and the positive recombinant virus was named as rBac-SS4-VP2. The insertion for the target gene into baculovirus genome was confirmed with PCR. SDS-PAGE and Western blotting revealed that the calculated protein of approximately 68 kDa was in the expressed in the insect cells. The Sf-9 cells infected with rBac-SS4-VP2 were stained positive against PPV antibody using the indirect immunofluorescence assay (IFA). Moreover, the virus particle self-assembly was observed under electron microscopy. 90 four-week-old mice were immunized by the recombinant protein coupled with different adjuvants alhydrogel, IMS and oil. VP2-specific ELISA antibodies, PPV-specific neutralizing antibody, somatostatin antibody and growth hormone levels were examined to evaluate the immunogenicity of this virus like particle. Results indicated that mice groups immunized rSS4-VP2 protein with alhydrogel and IMS developed similar humoral immune response comparing with inactived PPV vaccine. Mice group immunized with rSS4-VP2 generated higher level of SS antibody and growth hormone comparing with negative control, mice receiving rSS4-VP2 with alhydrogel developed the highest antibody titre than all

  15. The Development of Analogical Reasoning Processes.

    Science.gov (United States)

    Sternberg, Robert J.; Rifkin, Bathsheva

    1979-01-01

    Two experiments were conducted to test the generalizability to children of a theory of analogical reasoning processes, originally proposed for adults, and to examine the development of analogical reasoning processes in terms of five proposed sources of cognitive development. (MP)

  16. 16-channel analog store and multiplexer unit

    Energy Technology Data Exchange (ETDEWEB)

    Brossard, M; Kulka, Z [Clermont-Ferrand-2 Univ., 63 - Aubiere (France). Lab. de Physique Corpusculaire

    1979-03-15

    A 16-channel analog store and multiplexer unit is described. The unit enables storing and selection of analog information which is then digitally encoded by single ADC. This solution becomes economically attractive particularly in multidetector pulse height analysis systems.

  17. Calcitonin gene-related peptide and somatostatin releases correlated with the area under the lafutidine concentration-time curve in human plasma.

    Science.gov (United States)

    Ikawa, K; Shimatani, T; Azuma, Y; Inoue, M; Morikawa, N

    2006-08-01

    To examine the effects of the histamine H(2)-receptor antagonist, lafutidine, at clinical dosage (10 mg tablet after a standardized meal) on plasma levels of the gastrointestinal peptides, calcitonin gene-related peptide (CGRP), somatostatin and gastrin. Six healthy male volunteers ate a standardized meal, and received either lafutidine orally at a dose of 10 mg or water only (control). Blood samples were taken before and up to 4 h after the drug administration. Plasma lafutidine concentrations were determined by high pressure liquid chromatography. Pharmacokinetic analysis of lafutidine was performed using one-compartmental model. The levels of immunoreactive substances of plasma CGRP, somatostatin and gastrin were measured by enzyme immunoassay, and the amount of peptide release was calculated by the trapezoidal method. Lafutidine significantly increased plasma CGRP levels at 1, 1.5, 2.5 and 4 h and the total amount of CGRP release (192 +/- 14.0 pg.h/mL) compared with the control group (128 +/- 21.5 pg.h/mL). Lafutidine significantly increased the plasma somatostatin levels at 1 and 1.5 h, and the total amount of somatostatin released (107 +/- 18.2 pg.h/mL) compared with the control (78.4 +/- 7.70 pg.h/mL). The area under the drug concentration-time curve (AUC) from 0 to 4 h after administration correlated well with the Delta-CGRP and Delta-somatostatin release but not with total amount of gastrin released. However, plasma gastrin levels were significantly elevated at 1.5 h after drug administration. Lafutidine at clinical dosage increases plasma CGRP and the somatostatin. The amounts released correlated with the AUC of lafutidine in humans. These results suggest that the increased release of CGRP and somatostatin may contribute to its gastroprotective and anti-acid secretory effect.

  18. Cysteamine induces cholecystokinin release from the duodenum. Evidence for somatostatin as an inhibitory paracrine regulator of cholecystokinin secretion in the rat

    International Nuclear Information System (INIS)

    Abucham, J.; Reichlin, S.

    1990-01-01

    To determine whether cholecystokinin secretion is regulated by endogenous somatostatin, somatostatin deficiency was induced in vivo with cysteamine (250 mg/kg body wt, IV) or anti-somatostatin antiserum in anaesthetized rats and in vitro with cysteamine (30 micrograms/mL) in a rat duodenum-incubation system. Cholecystokinin secretion was assessed in vivo by measuring amylase in duodenal perfusates collected at 10-minute intervals for 1 hour and in vitro by a carboxy-terminal radioimmunoassay. Cysteamine induced a marked decrease in duodenal immunoreactive somatostatin both in vivo (50%) and in vitro (60%). The rate of amylase secretion increased from 9.7 +/- 2.1 U (mean +/- SE) to 28.0 +/- 4.8 U at 20 minutes (P less than 0.001). The cholecystokinin-receptor antagonist CR-1392 abolished amylase response for 30 minutes, whereas the more potent antagonists Asperlicin (18.0 mg/kg body wt, IV) and L-364,718 (0.25 mg/kg body wt, IV) caused prolonged blockade. The rate of amylase secretion in gastrectomized animals increased from 7.2 +/- 2.0 U to 15.0 +/- 2.2 U 20 minutes after cysteamine administration (P less than 0.01), indicating that the effect was not due to the presence of gastrin. In vitro, cysteamine caused a nearly fourfold increase in cholecystokinin secretion compared with controls (63.1 +/- 4.9 vs. 15.2 +/- 3.7, respectively; P less than 0.001). In vivo immunoneutralization of circulating somatostatin with a high-affinity and high-capacity antiserum produced no significant change in the rate of amylase secretion. These results suggest that cholecystokinin secretion is tonically inhibited by somatostatin and that this effect is mediated by locally secreted (paracrine) but not by circulating somatostatin

  19. Union of 99m Tc-HYNIC-TOC at the somatostatin receptors in cells of pancreas cancer

    International Nuclear Information System (INIS)

    Rodriguez C, J.; Ramirez I, M.T.; Ferro F, G.; Pedraza L, M.

    2005-01-01

    The radiation toxic effects have been used in therapy however much 50 years. The absorbed radiation dose can be determined at cellular level using cancerous cell cultures. If the deposited In vitro radiation dose coming from similar activities of several therapeutic radiopharmaceuticals it can compare it will be possible to choose the therapeutic radiopharmaceutical that it offers better dosimetric characteristics for the patient. The objective of this original investigation was to determine the union percentage of the octreotide 99m Tc-HYNlC-TOC to the somatostatin receivers in cells of cancer pancreas as well as the internalization, externalization and cellular viability. It was used the octapeptide, (octreotide, TOC) labelled with 99m Tc by means of the HYNIC chelating agent (6-hydrazine pyridine-3-carboxylic acid) and 3 cellular lines of murine pancreas cancer (AR42J), of cancer of human pancreas (CAPAN) and of one negative cellular line for somatostatin receivers (WRL-68). The 99m Tc-HYNIC-TOC was compared against two negative proofs for somatostatin receivers: the peptide 99m Tc-UBI and the 99m TcO 4 . The cellular lines were conserved in the synthetic media Dulbecco-Eagle. After 2, 4 and 24 h of exhibition to the radiation, the cells are picked up and its are determined the viability by count in a Neubauer camera using tripan blue. In the same times it was calculated the union percentage of the radiopharmaceutical to the cells and the internalization (union to the cytoplasm) and the externalization (union to membrane receivers). With those figures it was calculated the absorbed radiation dose at cellular level. Results: At 4 hours the union percentage of the 99m Tc-HYNlC-TOC to the AR42-J cells was 6.83 times greater than for the WRL-68 control cells of human papilloma, (without receivers of the somatostatin) and for the CAPAN them 4 times greater than for the same cells used as negative control, for the case of the 99m Tc-UBI and the 99m TcO 4 one doesn

  20. Atheism and Analogy: Aquinas Against the Atheists

    OpenAIRE

    Linford, Daniel J.

    2014-01-01

    In the 13th century, Thomas Aquinas developed two models for how humans may speak of God - either by the analogy of proportion or by the analogy of proportionality. Aquinas's doctrines initiated a theological debate concerning analogy that spanned several centuries. In the 18th century, there appeared two closely related arguments for atheism which both utilized analogy for their own purposes. In this thesis, I show that one argument, articulated by the French materialist Paul-Henri Thiry Bar...

  1. Enhancing programming logic thinking using analogy mapping

    Science.gov (United States)

    Sukamto, R. A.; Megasari, R.

    2018-05-01

    Programming logic thinking is the most important competence for computer science students. However, programming is one of the difficult subject in computer science program. This paper reports our work about enhancing students' programming logic thinking using Analogy Mapping for basic programming subject. Analogy Mapping is a computer application which converts source code into analogies images. This research used time series evaluation and the result showed that Analogy Mapping can enhance students' programming logic thinking.

  2. Analogies and the 5E Model

    Science.gov (United States)

    Orgill, Mary Kay; Thomas, Megan

    2007-01-01

    Science classes are full of abstract or challenging concepts that are easier to understand if an analogy is used to illustrate the points. Effective analogies motivate students, clarify students' thinking, help students overcome misconceptions, and give students ways to visualize abstract concepts. When they are used appropriately, analogies can…

  3. Science Teachers' Analogical Reasoning

    Science.gov (United States)

    Mozzer, Nilmara Braga; Justi, Rosária

    2013-01-01

    Analogies can play a relevant role in students' learning. However, for the effective use of analogies, teachers should not only have a well-prepared repertoire of validated analogies, which could serve as bridges between the students' prior knowledge and the scientific knowledge they desire them to understand, but also know how to…

  4. The Micro-Category Account of Analogy

    Science.gov (United States)

    Green, Adam E.; Fugelsang, Jonathan A.; Kraemer, David J. M.; Dunbar, Kevin N.

    2008-01-01

    Here, we investigate how activation of mental representations of categories during analogical reasoning influences subsequent cognitive processing. Specifically, we present and test the central predictions of the "Micro-Category" account of analogy. This account emphasizes the role of categories in aligning terms for analogical mapping. In a…

  5. Changes in pancreatic somatostatin content in spontaneously diabetic mice, as determined by radioimmunoassay and immunohistochemical methods

    International Nuclear Information System (INIS)

    Makino, H.; Matsushima, Y.; Kanatsuka, A.; Yamamoto, M.; Kumagai, A.; Nishimura, M.

    1979-01-01

    A specific RIA for somatostatin (SRIF) was used to determine the SRIF content of the pancreas and hypothalamus in spontaneously diabetic C57BL/KsJ dbdb and C57BL/6J obob mice. In addition, SRIF- and glucagon-containing cells were examined in the pancreatic islets with an immunohistochemical technique. In dbdb mice, immunoassayable pancreatic SRIF content was increased, as was the number of SRIF- or glucagon-containing cells. In obob mice, immunoassayable pancreatic SRIF content was also increased, but no increase was noted in the number of SRIF- or glucagon-containing cells. The hypothalamic SRIF content of either strain was not different from that of controls. These results regarding pancreatic SRIF content were in accord with some but not all previous reports. These differences may be related to the age of the mice or to the conditions in which they were bred. The pancreatic SRIF increase in both dbdb and obob mice may be attributable to hyperglucagonemia, hyperglycemia, or a decrease in insulin action. Further work is necessary to clearly delineate the mechanism

  6. Vasoactive intestinal peptide and somatostatin in the plasma and sigmoid mucosa in irritable bowel syndrome

    International Nuclear Information System (INIS)

    Zhang Ru; Wang Fuxian

    2004-01-01

    To investigate the possible role and clinical significance of vasoactive intestinal peptide (VIP) and somatostatin(SS) in the irritable bowel syndrome (IBS), the VIP and SS in the plasma and sigmoid mucosa were measured by radioimmunoassay in the control group and the IBS group. The VIP concentration in the plasma and sigmoid mucosa of the IBS patients with constipation was significantly higher than that of the control group (P<0.01), while that of the IBS patients with diarrhea was significantly lower than that of the control group (P<0.05). The SS concentration in two sites was significantly elevated in IBS patients of both types and was significantly higher in IBS with constipation than in IBS with diarrhea (P<0.05). Conclusion: The VIP and SS in IBS are abnormal, which might play a role in the pathogenesis of IBS. The plasma and mucosa concenration of VIP and SS in two kinds of IBS patients are significantly different, which indicates that there might be different pathophysiological basis involved in the pathogenesis of the two kinds of IBS patients. (authors)

  7. Differential Receptive Field Properties of Parvalbumin and Somatostatin Inhibitory Neurons in Mouse Auditory Cortex.

    Science.gov (United States)

    Li, Ling-Yun; Xiong, Xiaorui R; Ibrahim, Leena A; Yuan, Wei; Tao, Huizhong W; Zhang, Li I

    2015-07-01

    Cortical inhibitory circuits play important roles in shaping sensory processing. In auditory cortex, however, functional properties of genetically identified inhibitory neurons are poorly characterized. By two-photon imaging-guided recordings, we specifically targeted 2 major types of cortical inhibitory neuron, parvalbumin (PV) and somatostatin (SOM) expressing neurons, in superficial layers of mouse auditory cortex. We found that PV cells exhibited broader tonal receptive fields with lower intensity thresholds and stronger tone-evoked spike responses compared with SOM neurons. The latter exhibited similar frequency selectivity as excitatory neurons. The broader/weaker frequency tuning of PV neurons was attributed to a broader range of synaptic inputs and stronger subthreshold responses elicited, which resulted in a higher efficiency in the conversion of input to output. In addition, onsets of both the input and spike responses of SOM neurons were significantly delayed compared with PV and excitatory cells. Our results suggest that PV and SOM neurons engage in auditory cortical circuits in different manners: while PV neurons may provide broadly tuned feedforward inhibition for a rapid control of ascending inputs to excitatory neurons, the delayed and more selective inhibition from SOM neurons may provide a specific modulation of feedback inputs on their distal dendrites. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Morphological Imaging in the Localization of Neuroendocrine Gastroenteropancreatic Tumors Found by Somatostatin Receptor Scintigraphy

    International Nuclear Information System (INIS)

    Saga, T.; Doi, R.; Endo, K.; Shimatsu, A.; Koizumi, K.; Ichikawa, T.; Yamamoto, K.; Noguchi, S.; Ishibashi, M.; Machinami, R.; Nakamura, K.; Sakahara, H.

    2005-01-01

    Purpose: To evaluate the necessity of morphological images (MI) in reading somatostatin receptor scintigraphy (SRS) in patients with suspected neuroendocrine gastroenteropancreatic (GEP) tumors. Material and Methods: A Japanese multicenter clinical trial of SRS was conducted in 40 patients with suspected GEP tumors. Three experienced radiologists interpreted the images in three separate sessions in a blinded manner (1: SRS images alone, 2: MI alone, 3: SRS and MI analyzed simultaneously), and the reading results of each session were compared. In addition, the diagnostic abilities of SRS, MI and SRS alone and simultaneous SRS and MI readings were compared for patients where final diagnosis was obtained. Results: SRS detected more suspected lesions (positive or inconclusive uptake) than morphological images did (51 vs 27 lesions), but included many physiological uptakes detected as positive or inconclusive uptakes. Combined reading of SRS and morphological images helped to correctly recognize these physiological uptakes, and also helped in determining the anatomical localization of the abnormal uptakes. Combined reading of SRS and morphological images gave the highest diagnostic impact. Conclusion: The sensitivity of SRS with regard to GEP is high. However the specificity is very low. Morphologic imaging is necessary for the exclusion of physiological uptake and correct anatomic location of an abnormal tracer uptake. The combined reading of SRS and morphologic imaging studies gives the highest diagnostic impact

  9. Novel sst2-selective somatostatin agonists. Three-dimensional consensus structure by NMR

    Science.gov (United States)

    Grace, Christy Rani R.; Erchegyi, Judit; Koerber, Steven C.; Reubi, Jean Claude; Rivier, Jean; Riek, Roland

    2008-01-01

    The three-dimensional NMR structures of six octapeptide agonist analogues of somatostatin (SRIF) in the free form are described. These analogues, with the basic sequence H-DPhe/Phe2-c[Cys3-Xxx7-DTrp8-Lys9-Thr10-Cys14]-Thr-NH2 (the numbering refers to the position in native SRIF), with Xxx7 being Ala/Aph, exhibit potent and highly selective binding to human SRIF type 2 (sst2) receptors. The backbone of these sst2-selective analogues have the usual type-II’ β-turn reported in the literature for sst2/3/5-subtype-selective analogues. Correlating biological results and NMR studies led to the identification of the side chains of DPhe2, DTrp8 and Lys9 as the necessary components of the sst2 pharmacophore. This is the first study to show that the aromatic ring at position 7 (Phe7) is not critical for sst2 binding and that it plays an important role in sst3 and sst5 binding. This pharmacophore is therefore different from that proposed by others for sst2/3/5 analogues. PMID:16854054

  10. SPECT/CT with radiolabeled somatostatin analogues in the evaluation of systemic granulomatous infections.

    Science.gov (United States)

    Monteiro, Paulo Henrique Silva; de Souza, Thiago Ferreira; Moretti, Maria Luiza; Resende, Mariangela Ribeiro; Mengatti, Jair; de Lima, Mariana da Cunha Lopes; Santos, Allan Oliveira; Ramos, Celso Darío

    2017-01-01

    To evaluate SPECT/CT with radiolabeled somatostatin analogues (RSAs) in systemic granulomatous infections in comparison with gallium-67 ( 67 Ga) citrate scintigraphy. We studied 28 patients with active systemic granulomatous infections, including tuberculosis, paracoccidioidomycosis, pneumocystosis, cryptococcosis, aspergillosis, leishmaniasis, infectious vasculitis, and an unspecified opportunistic infection. Of the 28 patients, 23 had started specific treatment before the study outset. All patients underwent whole-body SPECT/CT imaging: 7 after injection of 99m Tc-EDDA-HYNIC-TOC, and 21 after injection of 111 In-DTPA-octreotide. All patients also underwent 67 Ga citrate imaging, except for one patient who died before the 67 Ga was available. In 20 of the 27 patients who underwent imaging with both tracers, 27 sites of active disease were detected by 67 Ga citrate imaging and by SPECT/CT with an RSA. Both tracers had negative results in the other 7 patients. RSA uptake was visually lower than 67 Ga uptake in 11 of the 20 patients with positive images and similar to 67 Ga uptake in the other 9 patients. The only patient who did not undergo 67 Ga scintigraphy underwent 99m Tc-EDDA-HYNIC-TOC SPECT/CT-guided biopsy of a lung cavity with focal RSA uptake, which turned to be positive for aspergillosis. SPECT/CT with 99m Tc-EDDA-HYNIC-TOC or 111 In-DTPA-octreotide seems to be a good alternative to 67 Ga citrate imaging for the evaluation of patients with systemic granulomatous disease.

  11. Somatostatin receptor scintigraphy to predict the clinical evolution and therapeutic response of thyroid-associated ophthalmopathy

    International Nuclear Information System (INIS)

    Nocaudie, M.; Bailliez, A.; Itti, E.; Marchandise, X.

    1999-01-01

    Management of thyroid-associated ophthalmopathy remains a topic of controversy. Immunosuppressive treatments have to be applied at peak disease activity and before criteria of severity develop. Expression of somatostatin receptors on activated lymphocytes allows scintigraphic imaging with indium-111 pentetreotide. We conducted a prospective study with 17 patients who presented severe ophthalmopathy (11 Graves' disease, four Hashimoto's thyroiditis, two isolated in appearance: Means' syndrome). Each patient underwent hormonal (free T 3 and TSH) and immunological (TBII) assessment, an orbital computed tomography scan or magnetic resonance imaging, a visual functional examination and 111 In-pentetreotide orbital scintigraphy before undergoing treatment by steroids and/or radiotherapy, independently of scintigraphic results. At 4 and 24 h after the intravenous injection of 111 MBq of 111 In-pentetreotide, planar imaging centred on the head and neck (anterior and both lateral views) was carried out. Retrobulbar uptake was assessed by visual semi-quantitative analysis (score given by two independent trained observers) and by quantitative analyses (regions of interest, orbit/brain uptake indices). Patients were ophthalmologically followed up for 6 months and then classified as improved or not. Visual semi-quantitative analysis of 4-h/24-h planar images was correlated with the ophthalmological evolution (χ 2 test, P 111 In-pentetreotide scintigraphy requires further developments, including quantitative single-photon emission tomographic acquisition, if its role as a guide to therapeutic strategy in thyroid-associated ophthalmopathy is to be confirmed. (orig.)

  12. Ectopic ACTH secretion due to a bronchopulmonary carcinoid localized by somatostatin receptor scintigraphy.

    Science.gov (United States)

    Iser, G; Pfohl, M; Dörr, U; Weiss, E M; Seif, F J

    1994-11-01

    We present the case of a 65-year-old woman with an adrenocorticotropic hormone (ACTH) secreting bronchopulmonary carcinoid. This patient showed the typical long history of Cushing's syndrome, including hypokaliemia, impaired glucose tolerance, high levels of ACTH and beta-endorphin, and coproduction of other peptides. At the onset of clinical symptoms in 1979 an adrenal adenoma was suspected, and left-sided adrenalectomy was performed. The symptoms soon recurred, and the diagnosis of ACTH-dependent Cushing's syndrome was made. As no ACTH-secreting tumor was found, the right adrenal was resected, and the patient was followed up regularly. Fourteen years later chest roentgenography and computed tomography revealed a para-aortic pulmonary lesion, which was suspicious for a bronchopulmonary carcinoid. ACTH and beta-endorphin were excessively, pancreatic polypeptide slightly elevated at that time. The final diagnosis was made using somatostatin receptor scintigraphy which confirmed the hormonal activity of the suspicious lesion; no additional focus was found. This method turned out to be not only a useful additional localization technique but also a promising tool for characterization and staging of a suspected ACTH-producing carcinoid. The tumor was resected curatively, and the diagnosis was confirmed histologically.

  13. Pathophysiology of GPCR Homo- and Heterodimerization: Special Emphasis on Somatostatin Receptors

    Directory of Open Access Journals (Sweden)

    Rishi K. Somvanshi

    2012-04-01

    Full Text Available G-protein coupled receptors (GPCRs are cell surface proteins responsible for translating >80% of extracellular reception to intracellular signals. The extracellular information in the form of neurotransmitters, peptides, ions, odorants etc is converted to intracellular signals via a wide variety of effector molecules activating distinct downstream signaling pathways. All GPCRs share common structural features including an extracellular N-terminal, seven-transmembrane domains (TMs linked by extracellular/intracellular loops and the C-terminal tail. Recent studies have shown that most GPCRs function as dimers (homo- and/or heterodimers or even higher order of oligomers. Protein-protein interaction among GPCRs and other receptor proteins play a critical role in the modulation of receptor pharmacology and functions. Although ~50% of the current drugs available in the market target GPCRs, still many GPCRs remain unexplored as potential therapeutic targets, opening immense possibility to discover the role of GPCRs in pathophysiological conditions. This review explores the existing information and future possibilities of GPCRs as tools in clinical pharmacology and is specifically focused for the role of somatostatin receptors (SSTRs in pathophysiology of diseases and as the potential candidate for drug discovery.

  14. Circadian modulation of anxiety: a role for somatostatin in the amygdala.

    Directory of Open Access Journals (Sweden)

    Anne Albrecht

    Full Text Available Pharmacological evidence suggests that the neuropeptide somatostatin (SST exerts anxiolytic action via the amygdala, but findings concerning the putative role of endogenous SST in the regulation of emotional responses are contradictory. We hypothesized that an endogenous regulation of SST expression over the course of the day may determine its function and tested both SST gene expression and the behavior of SST knock out (SST⁻/⁻ mice in different aversive tests in relation to circadian rhythm. In an open field and a light/dark avoidance test, SST⁻/⁻ mice showed significant hyperactivity and anxiety-like behavior during the second, but not during the first half of the active phase, failing to show the circadian modulation of behavior that was evident in their wild type littermates. Behavioral differences occurred independently of changes of intrinsically motivated activity in the home cage. A circadian regulation of SST mRNA and protein expression that was evident in the basolateral complex of the amygdala of wild type mice may provide a neuronal substrate for the observed behavior. However, fear memory towards auditory cue or the conditioning context displayed neither a time- nor genotype-dependent modulation. Together this indicates that SST, in a circadian manner and putatively via its regulation of expression in the amygdala, modulates behavior responding to mildly aversive conditions in mice.

  15. Pattern of somatostatin receptors expression in normal and bladder cancer tissue samples.

    Science.gov (United States)

    Karavitakis, Markos; Msaouel, Pavlos; Michalopoulos, Vassilis; Koutsilieris, Michael

    2014-06-01

    Known risks factors for bladder cancer progression and recurrence are limited regarding their prognostic ability. Therefore identification of molecular determinants of disease progression could provide with more specific prognostic information and could be translated into new approaches for biomarker development. In the present study we evaluated, the expression patterns of somatostatin receptors 1-5 (SSTRs) in normal and tumor bladder tissues. The expression of SSTR1-5 was characterized in 45 normal and bladder cancer tissue samples using reverse transcriptase-polymerase chain reaction (RT-PCR). SSTR1 was expressed in 24 samples, SSTR2 in 15, SSTR3 in 23, SSTR4 in 16 and SSTR5 in all but one sample. Bladder cancer tissue samples expressed lower levels of SSTR3. Co-expression of SSTRs was associated with superficial disease. Our results demonstrate, for the first time, that there is expression of SSTR in normal and bladder cancer urothelium. Further studies are required to evaluate the prognostic and therapeutic significance of these findings. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  16. Somatostatin receptor scintigraphy and magnetic resonance imaging in recurrent medullary thyroid carcinoma: A comparative study

    International Nuclear Information System (INIS)

    Doerr, U.; Wuerstlin, S.; Frank-Raue, K.; Raue, F.; Hehrmann, R.; Iser, G.; Scholz, M.; Guhl, L.; Buhr, H.J.; Bihl, H.

    1993-01-01

    In a prospective study, 18 patients with recurrent medullary thyroid carcinoma (MTC) underwent magnetic resonance imaging (MRI) of the neck and mediastinum and somatostatin receptor scintigraphy (SRS) with 111 In-labeled pentetreotide. In nine patients with macroscopic MTC, 17 corresponding lesions were found on MRI and SRS; in addition, 13 suspicious lesions were seen on SRS only. Histological confirmation was available for 19 metastatic lesions, showing MRI to be true positive in 13 metastases, SRS in 18. In minimal residual disease (n=10), MRI and SRS were compared with the histological findings in three patients and with selective venous catheterization (SVC) in seven patients. Corresponding findings on MRI and SVC were seen in one of seven, whereas SRS and SVC showed concordant localization of tumor recurrence in five of seven. Histological examination demonstrated MTC tissue in one of three cases; MRI and SRS were false positive in one of three cases, while in the others the interpretation remained uncertain. In conclusion, SRS is a promising imaging modality for localization of MTC recurrence. MRI provides better spatial resolution and thus facilitates the planning of surgery for macroscopic metastases. In minimal residual disease, SRS turned out to be superior in detecting occult MTC recurrence, confirming SVC findings. (orig.)

  17. The liver plays an important role in the regulation of somatostatin-14 in the rat

    International Nuclear Information System (INIS)

    Raper, S.E.; Kothary, P.C.; Kokudo, N.; DelValle, J.; Eckhauser, F.E.

    1991-01-01

    Since little is known about the in vivo disposition of circulating somatostatin-14 (SRIF-14), we examined hepatic processing of SRIF-14 in the rat. Three minutes after the intraportal injection of iodine 125 ( 125 I)-labeled SRIF-14, 16.0 +/- 2.0% of the injected dose is localized to the liver. In the presence of unlabeled SRIF-14, hepatic uptake can be decreased by 68%. Five minutes after the intraportal injection of 125 I-SRIF-14, 9.5 +/- 1.4% of the tracer is localized to the liver, more than any other organ tested. Serial collections of bile reveal peak radioactivity at between 10 and 20 minutes. Simultaneous administration of unlabeled SRIF-14 decreases biliary radioactivity by 40%. HPLC analysis of radioactive bile reveals a chromatographic profile similar to that of intact SRIF and is 73% immunoprecipitable by an anti-SRIF antibody. Pretreatment with chloroquine, a lysosomal enzyme inhibitor, does not significantly decrease biliary radioactivity. We conclude that the data are consistent with saturable hepatic uptake and predominantly nonlysosomal transcellular transport

  18. Peripheral nervous system assessment in acromegaly patients under somatostatin analogue therapy.

    Science.gov (United States)

    Alibas, H; Gogas Yavuz, D; Kahraman Koytak, P; Uygur, M; Tanridag, T; Uluc, K

    2017-01-01

    Acromegaly is known to affect peripheral nervous system (PNS) causing carpal tunnel syndrome (CTS) and polyneuropathy. The frequency of these disorders and the evaluation methods vary among studies. In the present study, we aimed to examine PNS of acromegaly patients under somatostatin analogue (SSA) therapy. Forty-eight acromegaly patients (26 F/22 M, 45.58 ± 11.6 years) under SSA treatment and 44 healthy controls (25 F/19 M, 47.46 ± 8.7 years) were assessed by symptom questionnaires, neurologic examination and electrophysiological studies. 87.5 % of the acromegaly patients had at least one abnormal finding regarding PNS. With the incorporation of palm-wrist median nerve conduction velocity method, we detected CTS in 50 % of patients. Polyneuropathy was less frequent (29.2 %). Both conditions were independent from the coexisting diabetes mellitus (p = 0.22 for CTS, p = 0.71 for polyneuropathy). Polyneuropathy but not CTS was more common among biochemically uncontrolled acromegaly patients rather than those under control (p = 0.03; p = 0.68, respectively). Our findings emphasize the high prevalence of peripheral nervous system involvement in acromegaly patients under SSA therapy and importance of neurological evaluation of these patients. Early diagnosis and treatment of the disease may reduce the PNS involvement.

  19. Somatostatin receptor scintigraphy and intraoperative gamma probe detection in the localisation and treatment of pancreatic insulinoma

    International Nuclear Information System (INIS)

    Loh, Nelson K.; Macdonald, William B.; Dunne, Marina L.; Rao, Sudhakar

    2009-01-01

    Full text: Aims: We report a case of insulinoma that was successfully enucleated under radio-guidance after an initial unsuccessful laparotomy. This case highlights the utility of Somatostatin Receptor Scintigraphy (SRS) and gamma probe in the localisation and treatment of neuroendocrine tumours. Methods: The patient presented with recurrent hypoglycaemia. An abdominal CT scan identified a lesion in the uncinate process of the pancreas, however, laparotomy with use of intraoperative ultrasound failed to localise the lesion. SRS with SPECTICT was then requested by the surgical team with a view to radio-guided surgery. Results: SRS demonstrated an octreotide-avid tumour in the posterior uncinate process of the pancreas, and confirmed suitability for radio-guided surgery. At re-exploration, the surgeon was again unable to palpate the lesion or localise it with intraoperative ultrasound, however, the lesion was successfully detected and removed with the use of a gamma probe. A postoperative SRS confirmed complete excision and histopathology was diagnostic of insulinoma. Conclusion: This case highlights the utility of SRS in the intraoperative localisation and surgical excision of neuroendocrine tumours. The lesion was unable to be localised clinically or with intraoperative ultrasound but was successfully detected with scintigraphic techniques. The surgical team acknowledge that the use of a gamma probe enabled enucleation of the insulinoma, which obviated the need for an invasive Whipple's procedure.

  20. Somatostatin receptor expression in Merkel cell carcinoma as target for molecular imaging

    International Nuclear Information System (INIS)

    Buder, Kristina; Becker, Jürgen C; Lapa, Constantin; Kreissl, Michael C; Schirbel, Andreas; Herrmann, Ken; Schnack, Alexander; Bröcker, Eva-Bettina; Goebeler, Matthias; Buck, Andreas K

    2014-01-01

    Merkel cell carcinoma (MCC) is a rare cutaneous neoplasm with increasing incidence, aggressive behavior and poor prognosis. Somatostatin receptors (SSTR) are expressed in MCC and represent a potential target for both imaging and treatment. To non-invasively assess SSTR expression in MCC using PET and the radiotracers [ 68 Ga]DOTA-D-Phe 1 -Tyr 3 -octreotide (DOTATOC) or -octreotate (DOTATATE) as surrogate for tumor burden. In 24 patients with histologically proven MCC SSTR-PET was performed and compared to results of computed tomography (CT). SSTR-PET detected primary and metastatic MCC lesions. On a patient-based analysis, sensitivity of SSTR-PET was 73% for nodal metastases, 100% for bone, and 67% for soft-tissue metastases, respectively. Notably, brain metastases were initially detected by SSTR-PET in 2 patients, whereas liver and lung metastases were diagnosed exclusively by CT. SSTR-PET showed concordance to CT results in 20 out of 24 patients. Four patients (17%) were up-staged due to SSTR-PET and patient management was changed in 3 patients (13%). SSTR-PET showed high sensitivity for imaging bone, soft tissue and brain metastases, and particularly in combination with CT had a significant impact on clinical stage and patient management

  1. Detecting somatostatin receptor in breast tumor tissue and its clinical significance

    International Nuclear Information System (INIS)

    Zhang Yongjian; Yu Xian; Lin Wei; Ding Xuan; Huang Shizhang; Lu Guangming

    2002-01-01

    The authors observe the difference of somatostatin receptor (SSR) between benign and malignant breast tumor and the relation between SSR and estrogen receptor (ER) or progesterone receptor (PR) in breast tumor tissue, and to predict the clinical value of detecting breast tumor by SSR receptor imaging. These tissues excised from operation in breast tumor were divided into 4 groups: breast malignant tumor group (BMTG) and its control group (C1G), breast benign tumor group (BBTG) and its control group (C2G). SSR was detected by radioligand binding assay (RBA) and ER, PR by LsAB method in these groups. Results is: (1) The SSR express quantity is 108.6 +- 67.3 fmol/mg pr, 37.2 +- 9.6 fmol/mg pr, 43.4 +- 12.6 fmol/mg pr 33.9 +- 10.2 fmol/mg pr respectively in BMTG, C1G, BBTG, C2G. The SSR of BMTG is the most among these groups, the difference is obvious, P 0.05); (2) The correlation coefficient of SSR and ER is 0.859, SSR and PR is 0.750. Most breast tumor tissues express high density SSR, the authors suppose that malignant tumor can been distinguished from benign tumor preliminarily by SSR receptor imaging. There is a good correlation between SSR and ER, PR, detecting SSR may predict the quality of tumor and the prognosis of the patient

  2. Safety and tolerability of pasireotide long-acting release in acromegaly-results from the acromegaly, open-label, multicenter, safety monitoring program for treating patients who have a need to receive medical therapy (ACCESS) study.

    Science.gov (United States)

    Fleseriu, Maria; Rusch, Elisha; Geer, Eliza B

    2017-01-01

    Pasireotide long-acting release is a somatostatin analog that is indicated for treatment of patients with acromegaly. This analysis documents the safety of pasireotide long-acting release in patients with acromegaly enrolled in the ACCESS trial (ClinicalTrials.gov identifier: NCT01995734). ACCESS is an open-label, multicenter, single-arm, expanded-treatment protocol designed to provide patients access to pasireotide long-acting release pending regulatory approval. Patients received pasireotide long-acting release 40 mg administered intramuscularly every 28 days. The primary outcome was the proportion of patients having a treatment-emergent grade ≥3 or serious adverse event. Efficacy data were not collected. Forty-four adult patients with active acromegaly were enrolled in the study for an average of 37.6 weeks (range, 4-70 weeks). Twenty-five grade ≥3 treatment-emergent adverse events were reported in 11 patients (25.0 %), 3 of whom (27.3 %) experienced grade ≥3 hyperglycemia. In patients treated with pasireotide long-acting release for ≥3 months (n = 42), mean glycated hemoglobin and fasting plasma glucose levels increased significantly from 5.9 % and 100.4 mg/dL at baseline to 6.8 % and 135.9 mg/dL at 3 months, respectively. Ten patients (22.7 %) were treated with pasireotide long-acting release for ≥15 months, after which mean glycated hemoglobin and fasting plasma glucose levels were 6.3 % and 123 mg/dL, respectively. Twenty-one patients (48 %) initiated antidiabetic medication. Grade ≥3 adverse events (primary outcome) were reported in 25.0 % of acromegaly patients treated with pasireotide long-acting release in a clinical setting. Hyperglycemia-related adverse events were reported in 45.5 % of patients, but were typically manageable, supporting the role of pasireotide long-acting release as a safe treatment option for acromegaly patients.

  3. Are all analogies created equal? Prefrontal cortical functioning may predict types of analogical reasoning.

    Science.gov (United States)

    Chrysikou, Evangelia G; Thompson-Schill, Sharon L

    2010-06-01

    Abstract The proposed theory can account for analogies based on learned relationships between elements in the source and target domains. However, its explanatory power regarding the discovery of new relationships during analogical reasoning is limited. We offer an alternative perspective for the role of PFC in analogical thought that may better address different types of analogical mappings.

  4. Practical analog electronics for technicians

    CERN Document Server

    Kimber, W A

    2013-01-01

    'Practical Analog Electronics for Technicians' not only provides an accessible introduction to electronics, but also supplies all the problems and practical activities needed to gain hands-on knowledge and experience. This emphasis on practice is surprisingly unusual in electronics texts, and has already gained Will Kimber popularity through the companion volume, 'Practical Digital Electronics for Technicians'. Written to cover the Advanced GNVQ optional unit in electronics, this book is also ideal for BTEC National, A-level electronics and City & Guilds courses. Together with 'Practical Digit

  5. Resistive RAMs as analog trimming elements

    Science.gov (United States)

    Aziza, H.; Perez, A.; Portal, J. M.

    2018-04-01

    This work investigates the use of Resistive Random Access Memory (RRAM) as an analog trimming device. The analog storage feature of the RRAM cell is evaluated and the ability of the RRAM to hold several resistance states is exploited to propose analog trim elements. To modulate the memory cell resistance, a series of short programming pulses are applied across the RRAM cell allowing a fine calibration of the RRAM resistance. The RRAM non volatility feature makes the analog device powers up already calibrated for the system in which the analog trimmed structure is embedded. To validate the concept, a test structure consisting of a voltage reference is evaluated.

  6. Analog and mixed-signal electronics

    CERN Document Server

    Stephan, Karl

    2015-01-01

    A practical guide to analog and mixed-signal electronics, with an emphasis on design problems and applications This book provides an in-depth coverage of essential analog and mixed-signal topics such as power amplifiers, active filters, noise and dynamic range, analog-to-digital and digital-to-analog conversion techniques, phase-locked loops, and switching power supplies. Readers will learn the basics of linear systems, types of nonlinearities and their effects, op-amp circuits, the high-gain analog filter-amplifier, and signal generation. The author uses system design examples to motivate

  7. Analog circuit design art, science, and personalities

    CERN Document Server

    Williams, Jim

    1991-01-01

    Analog Circuit Design: Art, Science, and Personalities discusses the many approaches and styles in the practice of analog circuit design. The book is written in an informal yet informative manner, making it easily understandable to those new in the field. The selection covers the definition, history, current practice, and future direction of analog design; the practice proper; and the styles in analog circuit design. The book also includes the problems usually encountered in analog circuit design; approach to feedback loop design; and other different techniques and applications. The text is

  8. CXCL14-like Immunoreactivity Exists in Somatostatin-containing Endocrine Cells, and in the Lamina Propria and Submucosal Somatostatinergic Nervous System of Mouse Alimentary Tract.

    Science.gov (United States)

    Suzuki, Hirohumi; Yamada, Kentaro; Matsuda, Yasuhiro; Onozuka, Minoru; Yamamoto, Toshiharu

    2017-12-26

    In the present study, we investigated the distribution of CXCL14 immunoreactive endocrine cells and neurons in mouse alimentary tract by immunohistochemistry. CXCL14 immunoreactive endocrine cells were found as closed-type cells in the stomach and open-type cells in the small intestine. The immunostaining of these endocrine cells corresponded with that of the somatostatin-containing endocrine cells. Only a few CXCL14 immunoreactive endocrine cells were seen in the large intestine. CXCL14 immunoreactive fibers were observed in the muscular layer from the stomach to the rectum with most abundance in the rectum. Many CXCL14 immunoreactive fibers were observed in the lamina propria and submucosal layer from the duodenum to the rectum with most abundance in the rectum; these fibers corresponded to the somatostatin-containing nerve fibers. Some CXCL14 immunoreactive neuronal somata that were also immuno-positive for somatostatin, were noted in the submucosal layer of the rectum. However, the remaining parts of the alimentary tract presented with almost negligible immunoreactive somata. The co-localization of CXCL14 and somatostatin suggests that CXCL14 contributes to the function of somatostatin, which include the inhibition of other endocrine and exocrine cells and the enteric nervous systems.

  9. Pharmacokinetics and pharmacodynamics of insulin analogs in special populations with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Morello CM

    2011-12-01

    Full Text Available Candis M Morello1,21Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 2School of Pharmacy, University of California San Francisco, Veterans Affairs San Diego Healthcare System, San Diego, CA, USAIntroduction: The goal of insulin therapy in patients with either type 1 diabetes mellitus (T1DM or type 2 diabetes mellitus (T2DM is to match as closely as possible normal physiologic insulin secretion to control fasting and postprandial plasma glucose. Modifications of the insulin molecule have resulted in two long-acting insulin analogs (glargine and detemir and three rapid-acting insulins (aspart, lispro, and glulisine with improved pharmacokinetic/pharmacodynamic (PK/PD profiles. These agents can be used together in basal-bolus therapy to more closely mimic physiologic insulin secretion patterns.Methods: This study reviews effects of the multiple demographic and clinical parameters in the insulin analogs glargine, detemir, lispro, aspart, and glulisine in patients with T2DM. A search was conducted on PubMed for each major topic considered (effects of injection site, age, race/ethnicity, obesity, renal or hepatic dysfunction, pregnancy, exercise, drug interactions using the topic words and name of each type of insulin analog. Information was also obtained from the prescribing information for each insulin analog.Results: The PK/PD profiles for insulin analogs may be influenced by many variables including age, weight, and hepatic and renal function. However, these variables do not have equivalent effects on all long-acting or rapid-acting insulin analogs.Conclusion: Rapid-acting and long-acting insulin analogs represent major advances in treatment for patients with T2DM who require insulin therapy. However, there are potentially important PK and PD differences between the two long-acting agents and among the three rapid-acting insulin analogs, which should be considered when designing treatment regimens for

  10. Analogical reasoning in schizophrenic delusions.

    Science.gov (United States)

    Simpson, Jane; Done, D John

    2004-09-01

    Reasoning ability has often been argued to be impaired in people with schizophrenic delusions, although evidence for this is far from convincing. This experiment examined the analogical reasoning abilities of several groups of patients, including non-deluded and deluded schizophrenics, to test the hypothesis that performance by the deluded schizophrenic group would be impaired. Eleven deluded schizophrenics, 10 depressed subjects, seven non-deluded schizophrenics and 16 matched non-psychiatric controls, who were matched on a number of key variables, were asked to solve an analogical reasoning task. Performance by the deluded schizophrenic group was certainly impaired when compared with the depressed and non-psychiatric control groups though less convincingly so when compared with the non-deluded schizophrenic group. The impairment shown by the deluded schizophrenic group seemed to occur at the initial stage of the reasoning task. The particular type of impairment shown by the deluded subjects was assessed in relation to other cognitive problems already researched and the implications of these problems on reasoning tasks and theories of delusions was discussed.

  11. Reliability of analog quantum simulation

    Energy Technology Data Exchange (ETDEWEB)

    Sarovar, Mohan [Sandia National Laboratories, Digital and Quantum Information Systems, Livermore, CA (United States); Zhang, Jun; Zeng, Lishan [Shanghai Jiao Tong University, Joint Institute of UMich-SJTU, Key Laboratory of System Control and Information Processing (MOE), Shanghai (China)

    2017-12-15

    Analog quantum simulators (AQS) will likely be the first nontrivial application of quantum technology for predictive simulation. However, there remain questions regarding the degree of confidence that can be placed in the results of AQS since they do not naturally incorporate error correction. Specifically, how do we know whether an analog simulation of a quantum model will produce predictions that agree with the ideal model in the presence of inevitable imperfections? At the same time there is a widely held expectation that certain quantum simulation questions will be robust to errors and perturbations in the underlying hardware. Resolving these two points of view is a critical step in making the most of this promising technology. In this work we formalize the notion of AQS reliability by determining sensitivity of AQS outputs to underlying parameters, and formulate conditions for robust simulation. Our approach naturally reveals the importance of model symmetries in dictating the robust properties. To demonstrate the approach, we characterize the robust features of a variety of quantum many-body models. (orig.)

  12. Analog-to-digital conversion

    CERN Document Server

    Pelgrom, Marcel J. M

    2013-01-01

    This textbook is appropriate for use in graduate-level curricula in analog to digital conversion, as well as for practicing engineers in need of a state-of-the-art reference on data converters.  It discusses various analog-to-digital conversion principles, including sampling, quantization, reference generation, nyquist architectures and sigma-delta modulation.  This book presents an overview of the state-of-the-art in this field and focuses on issues of optimizing accuracy and speed, while reducing the power level. This new, second edition emphasizes novel calibration concepts, the specific requirements of new systems, the consequences of 45-nm technology and the need for a more statistical approach to accuracy.  Pedagogical enhancements to this edition include more than twice the exercises available in the first edition, solved examples to introduce all key, new concepts and warnings, remarks and hints, from a practitioner’s perspective, wherever appropriate.  Considerable background information and pr...

  13. Ga-66 labeled somatostatin analogue DOTA-DPhe1-Tyr3-octreotide as a potential agent for positron emission tomography imaging and receptor mediated internal radiotherapy of somatostatin receptor positive tumors

    International Nuclear Information System (INIS)

    Ugur, Oemer; Kothari, Paresh J.; Finn, Ronald D.; Zanzonico, Pat; Ruan, Shutian; Guenther, Ilonka; Maecke, Helmut R.; Larson, Steven M.

    2002-01-01

    Radionuclide labeled somatostatin analogues selectively target somatostatin receptor (SSTR)-expressing tumors as a basis for diagnosis and treatment of these tumors. Recently, a DOTA-functionalized somatostatin analogue, DOTATOC (DOTA-DPhe 1 -Tyr 3 -octreotide) has been developed. This compound has been shown to be superior to the other somatostatin analogues as indicated by its uniquely high tumor-to-non-target tissue ratio. DOTATOC can be labeled with a variety of radiometals including gallium radioisotopes. Gallium-66 is a positron emitting radionuclide (T 1/2 =9.5 hr; β + =56%), that can be produced in carrier free form by a low-beam energy cyclotron. In this study we investigated SSTR targeting characteristics of 66 Ga-DOTATOC in AR42J rat pancreas tumor implanted nude mice as a potential agent for diagnosis and receptor-mediated internal radiotherapy of SSTR-expressing tumors. We compared our results with 67 Ga- and 68 Ga- labeled DOTATOC. The radiolabeling procedure gave labeling yield ranged from 85-95% and radiochemical and chemical purity was >95%. In-vitro competitive binding curves and in-vivo competitive displacement studies with an excess of unlabeled peptide indicates that there is specific binding of the radioligand to SSTR. Animal biodistribution data and serial microPET TM images demonstrated rapid tumor uptake and rapid clearance from the blood and all tissues except kidney. Maximum % ID/g values for tumor were 10.0±0.7, 13.2±2.1 and 9.8±1.5 for 66 Ga-, 67 Ga-, and 68 Ga-DOTATOC, respectively. Calculated tumor, kidney and bone marrow doses for 66 Ga-DOTATOC based on biodistribution data were 178, 109 and 1.2 cGy/MBq, respectively. We conclude that 66 Ga labeled DOTATOC can be used for PET diagnosis and quantitative imaging-based dosimetry of SSTR positive tumors. 66 Ga-DOTATOC may also be used in higher doses for ablation of these tumors. However, kidney is the critical organ for toxicity (tumor/kidney ratio 1.64), and high kidney uptake must

  14. Ga-66 labeled somatostatin analogue DOTA-DPhe{sup 1}-Tyr{sup 3}-octreotide as a potential agent for positron emission tomography imaging and receptor mediated internal radiotherapy of somatostatin receptor positive tumors

    Energy Technology Data Exchange (ETDEWEB)

    Ugur, Oemer E-mail: ougur@hacettepe.edu.tr; Kothari, Paresh J.; Finn, Ronald D.; Zanzonico, Pat; Ruan, Shutian; Guenther, Ilonka; Maecke, Helmut R.; Larson, Steven M

    2002-02-01

    Radionuclide labeled somatostatin analogues selectively target somatostatin receptor (SSTR)-expressing tumors as a basis for diagnosis and treatment of these tumors. Recently, a DOTA-functionalized somatostatin analogue, DOTATOC (DOTA-DPhe{sup 1}-Tyr{sup 3}-octreotide) has been developed. This compound has been shown to be superior to the other somatostatin analogues as indicated by its uniquely high tumor-to-non-target tissue ratio. DOTATOC can be labeled with a variety of radiometals including gallium radioisotopes. Gallium-66 is a positron emitting radionuclide (T{sub 1/2} =9.5 hr; {beta}{sup +}=56%), that can be produced in carrier free form by a low-beam energy cyclotron. In this study we investigated SSTR targeting characteristics of {sup 66}Ga-DOTATOC in AR42J rat pancreas tumor implanted nude mice as a potential agent for diagnosis and receptor-mediated internal radiotherapy of SSTR-expressing tumors. We compared our results with {sup 67}Ga- and {sup 68}Ga- labeled DOTATOC. The radiolabeling procedure gave labeling yield ranged from 85-95% and radiochemical and chemical purity was >95%. In-vitro competitive binding curves and in-vivo competitive displacement studies with an excess of unlabeled peptide indicates that there is specific binding of the radioligand to SSTR. Animal biodistribution data and serial microPET{sup TM} images demonstrated rapid tumor uptake and rapid clearance from the blood and all tissues except kidney. Maximum % ID/g values for tumor were 10.0{+-}0.7, 13.2{+-}2.1 and 9.8{+-}1.5 for {sup 66}Ga-, {sup 67}Ga-, and {sup 68}Ga-DOTATOC, respectively. Calculated tumor, kidney and bone marrow doses for {sup 66}Ga-DOTATOC based on biodistribution data were 178, 109 and 1.2 cGy/MBq, respectively. We conclude that {sup 66}Ga labeled DOTATOC can be used for PET diagnosis and quantitative imaging-based dosimetry of SSTR positive tumors. {sup 66}Ga-DOTATOC may also be used in higher doses for ablation of these tumors. However, kidney is the

  15. Analogies between optical and quantum mechanical angular momentum.

    Science.gov (United States)

    Nienhuis, Gerard

    2017-02-28

    The insight that a beam of light can carry orbital angular momentum (AM) in its propagation direction came up in 1992 as a surprise. Nevertheless, the existence of momentum and AM of an electromagnetic field has been well known since the days of Maxwell. We compare the expressions for densities of AM in general three-dimensional modes and in paraxial modes. Despite their classical nature, these expressions have a suggestive quantum mechanical appearance, in terms of linear operators acting on mode functions. In addition, paraxial wave optics has several analogies with real quantum mechanics, both with the wave function of a free quantum particle and with a quantum harmonic oscillator. We discuss how these analogies can be applied.This article is part of the themed issue 'Optical orbital angular momentum'. © 2017 The Author(s).

  16. ACTS 2014

    DEFF Research Database (Denmark)

    Co-curator of ACTS 2014 together with Rasmus Holmboe, Judith Schwarzbart and Sanne Kofoed. ACTS is the Museum of Contemporary Art’s international bi-annual festival. ACTS was established in 2011 and, while the primary focus is on sound and performance art, it also looks toward socially oriented art....... For the 2014 festival, the museum has entered into a collaboration with the Department for Performance Design at Roskilde University – with continued focus on sound and performance art, and social art in public spaces. With ACTS, art moves out of its usual exhibition space and instead utilizes the city, its...... various possibilities and public spaces as a stage. ACTS takes place in and around the museum and diverse locations in Roskilde city. ACTS is partly curated by the museum staff and partly by guest curators. ACTS 2014 is supported by Nordea-fonden and is a part of the project The Museum goes downtown....

  17. Preparation, formulation and quality control of one step kit 99m Tc - EDDA/HYNIC-Tyr3-Octreotide as a peptide radiopharmaceutical for imaging somatostatin receptor positive tumors

    International Nuclear Information System (INIS)

    Gandomkar, M.; Najafi, R.; Sadat-Ebrahimi, E.; Babaei, M.H.

    2004-01-01

    The high expression of somatostatin receptors in many tumours, have made receptor scintigraphy with 11I n-DTPA-Octreotide a widely used procedure in nuclear medicine. Despite its clinical success, some limitation and drawbacks of radiolabelling with 11I n remain, especially those concerned with the cost, availability and physical decay properties of this radionuclide. 99m Tc - EDDA/HYNIC-Tyr 3 -Octreotide was studied as a new agent with the potential to replace octreoscan in somatostatin receptor scintigraphy. This hydrazino nicotinic acid derivatized somatostatin complex contains ethylenediamine N, N diacetic acid as a co-ligand resulting in a high in vitro and in vivo stability. High labeling yields (>90%) were achieved at high specific activities. Characterization via HPLC, biodistribution and receptor binding of the resulting complex are described. The formulation developed enables rapid and simple labeling of 99m Tc - EDDA/HYNIC-TOC in a manner suitable for clinical setting

  18. Study on the changes of serum levels of polypeptide growth factors (EGF, TGF-α) and related hormones (gastrin, somatostatin) in patients with peptic ulcer

    International Nuclear Information System (INIS)

    Cao Jianfan; Ma Yunbao; Zhang Xiaoyi

    2005-01-01

    Objective: To study the possible roles of EGF, TGF-α, gastrin and somatostatin in the pathogenesis of peptic ulcer by measuring the changes of serum levels of those four parameters in the patients with peptic ulcer. Methods: Serum levels of epidermal growth factor (EGF), transforming growth factor-α (TGF-α), gastrin (Gas) and somatostatin (SS) were measured with RIA in 30 patients with gastric ulcer, 32 patients with duodenal ulcer and 30 controls. Results: Serum levels of gastrin and EGF were significantly higher in the patients with peptic ulcer than those in the controls (both P 0.05). However, serum TGF-α levels were significantly lower in the ulcer patients than those in the controls (P<0.01). Conclusion: Changes of serum levels of gastrin, EGF and TGF-α were quite significant in the ulcer patients and determining of which might be of clinical meanings. Determination of somatostatin changes seemed to be of less importance. (authors)

  19. Tumor-associated macrophages in glioblastoma multiforme-a suitable target for somatostatin receptor-based imaging and therapy?

    Directory of Open Access Journals (Sweden)

    Constantin Lapa

    Full Text Available Glioblastoma multiforme (GBM is the most common primary brain tumor in adults. Tumor-associated macrophages (TAM have been shown to promote malignant growth and to correlate with poor prognosis. [1,4,7,10-tetraazacyclododecane-NN',N″,N'″-tetraacetic acid]-d-Phe1,Tyr3-octreotate (DOTATATE labeled with Gallium-68 selectively binds to somatostatin receptor 2A (SSTR2A which is specifically expressed and up-regulated in activated macrophages. On the other hand, the role of SSTR2A expression on the cell surface of glioma cells has not been fully elucidated yet. The aim of this study was to non-invasively assess SSTR2A expression of both glioma cells as well as macrophages in GBM.15 samples of patient-derived GBM were stained immunohistochemically for macrophage infiltration (CD68, proliferative activity (Ki67 as well as expression of SSTR2A. Anti-CD45 staining was performed to distinguish between resident microglia and tumor-infiltrating macrophages. In a subcohort, positron emission tomography (PET imaging using 68Ga-DOTATATE was performed and the semiquantitatively evaluated tracer uptake was compared to the results of immunohistochemistry.The amount of microglia/macrophages ranged from 50% in the tumor samples with the vast majority being resident microglial cells. A strong SSTR2A immunostaining was observed in endothelial cells of proliferating vessels, in neurons and neuropile. Only faint immunostaining was identified on isolated microglial and tumor cells. Somatostatin receptor imaging revealed areas of increased tracer accumulation in every patient. However, retention of the tracer did not correlate with immunohistochemical staining patterns.SSTR2A seems not to be overexpressed in GBM samples tested, neither on the cell surface of resident microglia or infiltrating macrophages, nor on the surface of tumor cells. These data suggest that somatostatin receptor directed imaging and treatment strategies are less promising in GBM.

  20. 99mTc-EDDA/HYNIC-TOC in management of patients with head and neck somatostatin receptor positive tumors.

    Science.gov (United States)

    Trogrlic, Mate; Tezak, Stanko

    2016-01-01

    Aim of this study was to determine the value of technetium-99m-hydrazinonicotinyl-Tyr3-octreotide (99mTc-ED-DA/HYNIC-TOC) in patients with somatostatin receptor (SSR) positive tumors of head and neck region. A total number of 16 patients were enrolled in this study. Planar whole body (WB) and single photon emission computed tomography (SPECT) images were acquired at 2 and 4 hours after the injection of approximately 670 MBq of 99mTc-EDDA/HYNIC-TOC. Additional single photon emission computed tomography/computed tomography (SPECT/CT) images of the head and neck region were acquired at 4h post tracer injection. Clinical and imaging follow up were taken as the reference standard. There were 10 female and 6 male patients of age 57.7 ± 12.9 years (58.5; 32-78) years. 99mTc-EDDA/HYNIC-TOC somatostatin receptor scintigraphy (SRS) was TP in 13 patients, TN in two and FP in one. Follow up period for SRS was 31.1 ± 19.4 (29; 2-63) months. 99mTc-EDDA/HYNIC-TOC scintigraphy provided additional information in 50% of patients, with impact on patient management in the same percentage of patients. Distant metastases were found in nine out of 16 patients (56%). 99mTc-EDDA/HYNIC-TOC SRS had sensitivity of 100% (75.3-100%), specificity of 66.7% (9.4-99.2%), accuracy of 93.7%, positive predictive value of 92.9% (66.1-99.8%), and negative predictive value of 100% (15.8-100%). Somatostatin receptor scintigraphy using 99mTc-EDDA/HYNIC-TOC is very useful imaging method in the evalu-ation of patients with SSR positive tumors of head and neck region.

  1. Somatostatin receptor scintigraphy using 99mTc-EDDA/HYNIC-TOC in patients with medullary thyroid carcinoma.

    Science.gov (United States)

    Czepczyński, Rafał; Parisella, Maria Gemma; Kosowicz, Jerzy; Mikołajczak, Renata; Ziemnicka, Katarzyna; Gryczyńska, Maria; Sowiński, Jerzy; Signore, Alberto

    2007-10-01

    Several new somatostatin analogues have been developed for the diagnosis and therapy of different tumours. Since somatostatin receptors are often over-expressed in medullary thyroid carcinoma (MTC), the aim of our study was to evaluate the utility of scintigraphy with the somatostatin analogue (99m)Tc-EDDA/HYNIC-TOC in MTC in comparison with other diagnostic techniques. Forty-five patients with MTC, aged 14-83 years, were investigated. Scintigraphy using (99m)Tc-EDDA/HYNIC-TOC (Tektrotyd) was performed 2 and 4 h post injection of 740 MBq (20 mCi) of the tracer. Other imaging techniques were also applied and analysed in individual cases (ultrasonography, computed tomography, (99m)Tc(V)-DMSA, (131)I-MIBG, (99m)Tc-MDP, (111)In-DTPA-octreotide and (18)F-FDG-PET) and compared with (99m)Tc-EDDA/HYNIC-TOC. In group 1 (eight patients before thyroidectomy), uptake of the tracer was found in the primary tumours. In group 2 (six patients with remission), a false positive result was found in one patient; in the remaining five patients, no pathological foci were visualised. In group 3 (31 patients with post-surgical hypercalcitoninaemia), scintigraphy was true positive in 23 patients (74.2%): uptake in the thyroid bed was found in five patients, in the lymph nodes in 18 and in bone metastases in four. Using (99m)Tc-EDDA/HYNIC-TOC scintigraphy, the overall sensitivity was 79.5%, specificity 83.3%, accuracy 80.0%, positive predictive value 96.9% and negative predictive value 38.5%. (99m)Tc-EDDA/HYNIC-TOC is clinically useful for scintigraphy in the follow-up of patients with MTC. It can be used in clinical practice for preoperative evaluation, for localisation of local recurrence or distant metastases and particularly for therapy decision making.

  2. Somatostatin receptor scintigraphy using 99mTc-EDDA/HYNIC-TOC in patients with medullary thyroid carcinoma

    International Nuclear Information System (INIS)

    Czepczynski, Rafal; Kosowicz, Jerzy; Ziemnicka, Katarzyna; Gryczynska, Maria; Sowinski, Jerzy; Parisella, Maria G.; Mikolajczak, Renata; Signore, Alberto

    2007-01-01

    Several new somatostatin analogues have been developed for the diagnosis and therapy of different tumours. Since somatostatin receptors are often over-expressed in medullary thyroid carcinoma (MTC), the aim of our study was to evaluate the utility of scintigraphy with the somatostatin analogue 99m Tc-EDDA/HYNIC-TOC in MTC in comparison with other diagnostic techniques. Forty-five patients with MTC, aged 14-83 years, were investigated. Scintigraphy using 99m Tc-EDDA/HYNIC-TOC (Tektrotyd) was performed 2 and 4 h post injection of 740 MBq (20 mCi) of the tracer. Other imaging techniques were also applied and analysed in individual cases (ultrasonography, computed tomography, 99m Tc(V)-DMSA, 131 I-MIBG, 99m Tc-MDP, 111 In-DTPA-octreotide and 18 F-FDG-PET) and compared with 99m Tc-EDDA/HYNIC-TOC. In group 1 (eight patients before thyroidectomy), uptake of the tracer was found in the primary tumours. In group 2 (six patients with remission), a false positive result was found in one patient; in the remaining five patients, no pathological foci were visualised. In group 3 (31 patients with post-surgical hypercalcitoninaemia), scintigraphy was true positive in 23 patients (74.2%): uptake in the thyroid bed was found in five patients, in the lymph nodes in 18 and in bone metastases in four. Using 99m Tc-EDDA/HYNIC-TOC scintigraphy, the overall sensitivity was 79.5%, specificity 83.3%, accuracy 80.0%, positive predictive value 96.9% and negative predictive value 38.5%. 99m Tc-EDDA/HYNIC-TOC is clinically useful for scintigraphy in the follow-up of patients with MTC. It can be used in clinical practice for preoperative evaluation, for localisation of local recurrence or distant metastases and particularly for therapy decision making. (orig.)

  3. Characterization of somatostatin receptors and associated signaling pathways in pancreas of R6/2 transgenic mice.

    Science.gov (United States)

    Somvanshi, Rishi K; Jhajj, Amrit; Heer, Michael; Kumar, Ujendra

    2018-02-01

    The present study describes the status of somatostatin receptors (SSTRs) and their colocalization with insulin (β), glucagon (α) and somatostatin (δ) producing cells in the pancreatic islets of 11weeks old R6/2 Huntington's Disease transgenic (HD tg) and age-matched wild type (wt) mice. We also determined expression of tyrosine hydroxylase (TH), glutamic acid decarboxylase (GAD) and presynaptic marker synaptophysin (SYP) in addition to signal transduction pathways associated with diabetes. In R6/2 mice, islets are relatively smaller in size, exhibit enhanced expression and nuclear inclusion of mHtt along with the loss of insulin, glucagon and somatostatin expression. In comparison to wt, R6/2 mice display enhanced mRNA for all SSTRs except SSTR2. In the pancreatic lysate, SSTR1, 4 and 5 immunoreactivity decreases whereas SSTR3 immunoreactivity increases with no discernible changes in SSTR2 immunoreactivity. Furthermore, at the cellular level, R6/2 mice exhibit a receptor specific distributional pattern of SSTRs like immunoreactivity and colocalization with β, α and δ cells. While GAD expression is increased, TH and SYP immunoreactivity was decreased in R6/2 mice, anticipating a cross-talk between the CNS and pancreas in diabetes pathophysiology. We also dissected out the changes in signaling pathway and found decreased activation and expression of PKA, AKT, ERK1/2 and STAT3 in R6/2 mice pancreas. These findings suggest that the impaired organization of SSTRs within islets may lead to perturbed hormonal regulation and signaling. These interconnected complex events might shed new light on the pathogenesis of diabetes in neurodegenerative diseases and the role of SSTRs in potential therapeutic intervention. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Multiparametric PET imaging in thyroid malignancy characterizing tumour heterogeneity: somatostatin receptors and glucose metabolism

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    Traub-Weidinger, Tatjana [Medical University of Vienna, Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Medical University of Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); Putzer, Daniel; Bale, Reto [Medical University of Innsbruck, Department of Radiology, Innsbruck (Austria); Guggenberg, Elisabeth von; Dobrozemsky, Georg; Nilica, Bernhard; Kendler, Dorota; Virgolini, Irene Johanna [Medical University of Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria)

    2015-12-15

    Radiolabelled somatostatin (SST) analogues have proven useful in diagnosing tumours positive for SST receptor (SSTR). As different subtypes of SSTR are expressed on the tumour cell surface, the choice of appropriate therapeutic SST analogue is crucial. We evaluated the SSTR status of thyroid cancer patients who had signs of progressive disease comparing different SSTR ligands for PET imaging to evaluate possible further therapeutic options. PET with {sup 68}Ga-radiolabelled SSTR ligands DOTA lanreotide (DOTA-LAN), DOTA-Tyr{sup 3} octreotide (DOTA-TOC) and {sup 18}F-FDG was performed in 31 patients with thyroid cancer (TC). These 31 patients comprised 18 with radioiodine non-avid differentiated TC (DTC) including 6 papillary TC (PTC), 8 follicular TC (FTC) and 4 oxyphilic TC (oxyTC), 5 with anaplastic TC (ATC), and 8 with medullary TC (MTC). The PET results were compared in a region-based evaluation. All patients underwent a PET study with {sup 68}Ga-DOTA-LAN, 28 patients with {sup 68}Ga-DOTA-TOC and 28 patients with {sup 18}F-FDG. A lack of SSTR expression was found in 13 of the 31 patients (42 %) with negative results with both SSTR tracers in 12 patients. Ambiguous results with both SSTR tracers were observed in one patient. High tracer uptake in SSTR PET images was seen in seven DTC patients (39 %; two PTC, three FTC, two oxyTC), in four ATC patients (80 %) and in six MTC patients (75 %). Lesions showing aerobic glycolysis on {sup 18}F-FDG PET were found in 24 of 28 patients (86 %) with corresponding positive results with {sup 68}Ga-DOTA-LAN in 35 % and with {sup 68}Ga-DOTA-TOC in 29 %. The heterogeneous SSTR profile of TC tumour lesions needs to be evaluated using different SSTR PET tracers to characterize more closely the SSTR subtype affinities in patients with progressive TC in order to further stratify therapy with SSTR therapeutics. (orig.)

  5. Growth-hormone and somatostatin effects on [75Se]selenomethionine uptake by the pancreas

    International Nuclear Information System (INIS)

    Atkins, H.L.; Som, P.

    1979-01-01

    The imaging of the pancreas with [ 75 Se]selenomethionine has a low rate of reliability. This study was carried out in order to elucidate some factors that may be important in affecting the degree of uptake of the tracer by the pancreas. Studies were carried out in animals to observe the effects of growth-hormone (GH), somatostatin (SRIF), L-DOPA, and apomorphine administration on the distribution of [ 75 Se]selenomethionine. Intravenously administered GH significantly depressed pancreatic uptake of Se-75 in mice and dogs and depressed the pancreas-to-liver concentration ratio (P/L). The effect of i.p. GH in mice was to decrease the P/L ratio, but the decrease in pancreatic uptake was not statistically significant. There was also a greater effect of GH in dogs than in mice, with pancreatic uptake decreasing from 5.60 +- 2.17% to 1.24 +- 0.96% and the P/L from 4.78 +- 1.85 to 0.97 +- 0.73. L-DOPA and apomorphine produced effects similar to GH in mice. SRIF in small doses had little effect, but in larger doses it enhanced pancreatic uptake, although not affecting P/L. The results indicate that hypothalamic factors may be important in affecting the function of the exocrine pancreas. Both L-DOPA and apomorphine are known to stimulate GH production through hypothalamic-pituitary pathways. In addition to suppressing GH release, SRIF may have direct effects on the exocrine pancreas

  6. SPECT/CT with radiolabeled somatostatin analogues in the evaluation of systemic granulomatous infections

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    Paulo Henrique Silva Monteiro

    2017-10-01

    Full Text Available Abstract Objective: To evaluate SPECT/CT with radiolabeled somatostatin analogues (RSAs in systemic granulomatous infections in comparison with gallium-67 (67Ga citrate scintigraphy. Materials and Methods: We studied 28 patients with active systemic granulomatous infections, including tuberculosis, paracoccidioidomycosis, pneumocystosis, cryptococcosis, aspergillosis, leishmaniasis, infectious vasculitis, and an unspecified opportunistic infection. Of the 28 patients, 23 had started specific treatment before the study outset. All patients underwent whole-body SPECT/CT imaging: 7 after injection of 99mTc-EDDA-HYNIC-TOC, and 21 after injection of 111In-DTPA-octreotide. All patients also underwent 67Ga citrate imaging, except for one patient who died before the 67Ga was available. Results: In 20 of the 27 patients who underwent imaging with both tracers, 27 sites of active disease were detected by 67Ga citrate imaging and by SPECT/CT with an RSA. Both tracers had negative results in the other 7 patients. RSA uptake was visually lower than 67Ga uptake in 11 of the 20 patients with positive images and similar to 67Ga uptake in the other 9 patients. The only patient who did not undergo 67Ga scintigraphy underwent 99mTc-EDDA-HYNIC-TOC SPECT/CT-guided biopsy of a lung cavity with focal RSA uptake, which turned to be positive for aspergillosis. Conclusion: SPECT/CT with 99mTc-EDDA-HYNIC-TOC or 111In-DTPA-octreotide seems to be a good alternative to 67Ga citrate imaging for the evaluation of patients with systemic granulomatous disease.

  7. Comparison of somatostatin analogue and metaiodobenzylguanidine scintigraphy for the detection of carcinoid tumours

    International Nuclear Information System (INIS)

    Nocaudie-Calzada, M.; Huglo, D.; Carnaille, B.; Proye, C.; Marchandise, X.

    1996-01-01

    The purpose of this prospective study was to compare the ability of radiolabelled somatostatin analogue (RSA) and metaiodobenzylguanidine (MIBG) scintigraphy to display carcinoid tumours. Forty patients were studied after radiological assessment based on clinical symptomatology. These patients had radiologically demonstrated tumours (n=28), resected tumours discovered to be of the carcinoid type (n=5) or clinically and biologically suspected carcinoid tumours (n=7). They underwent indium-111 DTPA-pentetreotide or iodine-123-Tyr-3-octreotide and 131 I-MIBG scintigraphy. The results were compared with those of complementary surgical or morphological examinations and analysed according to the site of the tumour and the symptomatology. In the case of 31 patients with a total of 55 tumoral sites, the sensitivity of the initial radiological assessment, of RSA and of MIBG was 96%, 86% and 64%, respectively, for the detection of at least one tumour per patient, but 51%, 85% and 51%, respectively, for the total number of sites. No site was detected solely by MIBG. The concordance between RSA and MIBG was better when all sites were considered (kappa index+0.44) than for only extrahepatic abdominal tumoral sites (kappa index+0.095). Abdominal, thoracic or bone marrow tumours were more easily detected with RSA than with MIBG. Hepatic invasion (21 cases) was more easily detected by radiology (sensitivity 100%) than by RSA and MIBG, both of which displayed a sensitivity of 80%, but with differences in uptake intensity. Tumour detection using MIBG was more significantly linked with flush (P 0.10). In the assessment of carcinoid tumours, RSA scintigraphy should be carried out initially (just after hepatic ultrasonography) and supplemented by MIBG, as comparison of the studies serves to guide therapeutic options and might be valuable for prognosis. (orig.). With 2 figs., 3 tabs

  8. SPECT/CT with radiolabeled somatostatin analogues in the evaluation of systemic granulomatous infections

    International Nuclear Information System (INIS)

    Monteiro, Paulo Henrique Silva; Souza, Thiago Ferreira de; Moretti, Maria Luiza; Resende, Mariangela Ribeiro; Lima, Mariana da Cunha Lopes de; Santos, Allan Oliveira; Ramos, Celso Darío

    2017-01-01

    Objective: To evaluate SPECT/CT with radiolabeled somatostatin analogues (RSAs) in systemic granulomatous infections in comparison with gallium-67 ( 67 Ga) citrate scintigraphy. Materials And Methods: We studied 28 patients with active systemic granulomatous infections, including tuberculosis, paracoccidioidomycosis, pneumocystosis, cryptococcosis, aspergillosis, leishmaniasis, infectious vasculitis, and an unspecified opportunistic infection. Of the 28 patients, 23 had started specific treatment before the study outset. All patients underwent whole-body SPECT/CT imaging: 7 after injection of 99m Tc-EDDA-HYNIC-TOC, and 21 after injection of 111 In-DTPA-octreotide. All patients also underwent 67 Ga citrate imaging, except for one patient who died before the 67 Ga was available. Results: In 20 of the 27 patients who underwent imaging with both tracers, 27 sites of active disease were detected by 67 Ga citrate imaging and by SPECT/CT with an RSA. Both tracers had negative results in the other 7 patients. RSA uptake was visually lower than 67 Ga uptake in 11 of the 20 patients with positive images and similar to 67 Ga uptake in the other 9 patients. The only patient who did not undergo 67 Ga scintigraphy underwent 99m Tc-EDDA-HYNIC-TOC SPECT/CT-guided biopsy of a lung cavity with focal RSA uptake, which turned to be positive for aspergillosis. Conclusion: SPECT/CT with 99m Tc-EDDA-HYNIC-TOC or 111 In-DTPA-octreotide seems to be a good alternative to 67 Ga citrate imaging for the evaluation of patients with systemic granulomatous disease. (author)

  9. Attitudes and preferences in patients with acromegaly on long-term treatment with somatostatin analogues

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    Cecilia Follin

    2016-08-01

    Full Text Available Introduction: Patients with acromegaly can be treated with surgery, medical therapy and/or radiation therapy. For the patients not being cured with surgery, treatment with somatostatin analogues (SSAs is the primary therapy. SSA can be taken by self- or partner-administered injections in addition to being given by a nurse at a clinic. The aim was to assess if patients with acromegaly prefer self-injections and to investigate their attitudes towards long-term medical therapy. Method: All patients in the southern medical region of Sweden with a diagnosis of acromegaly and treated with SSA were eligible for the study (n = 24. The study is based on a questionnaire asking about the patients’ attitudes and preferences for injections with SSA, including their attitudes towards self-injection with SSA. Results: The patients’ (23 included median age was 68.5 years and the patients had been treated with SSA for 13 (1–38 years. One patient was currently self-injecting. All of the other patients were receiving injections from a nurse at a clinic. Three patients preferred self-injections, one preferred partner injections and 19 patients did not prefer self- or partner injections. The most frequent arguments to not preferring self-injections were ‘feeling more secure with an educated nurse’ and ‘preferring regular contact with a specialised nurse’. Conclusion: Patients with acromegaly prefer regular contact with the endocrine team to the independence offered by self-injections. These findings might mirror the patients’ desires for continuity and safety. We need to address patients’ concerns regarding injections with SSA and support them in their choices.

  10. Inverse expression of somatostatin and CXCR4 chemokine receptors in gastroenteropancreatic neuroendocrine neoplasms of different malignancy

    Science.gov (United States)

    Kaemmerer, Daniel; Träger, Tina; Hoffmeister, Maike; Sipos, Bence; Hommann, Merten; Sänger, Järg; Schulz, Stefan; Lupp, Amelie

    2015-01-01

    Introduction Somatostatin receptors (SSTR) are widely distributed in well-differentiated neuroendocrine neoplasms (NEN) and serve as primary targets for diagnostics and treatment. An overexpression of the chemokine receptor CXCR4, in contrast, is considered to be present mainly in highly proliferative and advanced tumors. Comparative data are still lacking, however, for neuroendocrine carcinomas (NEC). Methods SSTR subtype (1, 2A, 3, 5) and CXCR4 expression was evaluated in G1 (n = 31), G2 (n = 47), and low (G3a; Ki-67: 21–49%; n = 21) and highly proliferative (G3b; Ki-67: >50%, n = 22) G3 (total n = 43) gastroenteropancreatic NEN samples by performing immunohistochemistry with monoclonal rabbit anti-human anti-SSTR and anti-CXCR4 antibodies, respectively, and was correlated with clinical data. Results Both CXCR4 and SSTR were widely expressed in all tumors investigated. CXCR4 expression differed significantly between the G1 and G3 specimens and within the G3 group (G3a to G3b), and was positively correlated with Ki-67 expression. SSTR2A, in contrast, exhibited an inverse association with Ki-67. SSTR2A was highly expressed in G1 and G2 tumors, but was significantly less abundant in G3 carcinomas. Additionally, SSTR1 expression was higher in G3a than in G3b tumors. Conclusion We observed an elevation in CXCR4 and a decrease in SSTR2A expression with increasing malignancy. Interestingly, 23% of the G3 specimens had strong SSTR2A expression. Because CXCR4 was strongly expressed in highly proliferative G3 carcinomas, it is an interesting new target and needs to be validated in larger studies. PMID:26259237

  11. Somatostatin-Positive Gamma-Aminobutyric Acid Interneuron Deficits in Depression: Cortical Microcircuit and Therapeutic Perspectives.

    Science.gov (United States)

    Fee, Corey; Banasr, Mounira; Sibille, Etienne

    2017-10-15

    The functional integration of external and internal signals forms the basis of information processing and is essential for higher cognitive functions. This occurs in finely tuned cortical microcircuits whose functions are balanced at the cellular level by excitatory glutamatergic pyramidal neurons and inhibitory gamma-aminobutyric acidergic (GABAergic) interneurons. The balance of excitation and inhibition, from cellular processes to neural network activity, is characteristically disrupted in multiple neuropsychiatric disorders, including major depressive disorder (MDD), bipolar disorder, anxiety disorders, and schizophrenia. Specifically, nearly 3 decades of research demonstrate a role for reduced inhibitory GABA level and function across disorders. In MDD, recent evidence from human postmortem and animal studies suggests a selective vulnerability of GABAergic interneurons that coexpress the neuropeptide somatostatin (SST). Advances in cell type-specific molecular genetics have now helped to elucidate several important roles for SST interneurons in cortical processing (regulation of pyramidal cell excitatory input) and behavioral control (mood and cognition). Here, we review evidence for altered inhibitory function arising from GABAergic deficits across disorders and specifically in MDD. We then focus on properties of the cortical microcircuit, where SST-positive GABAergic interneuron deficits may disrupt functioning in several ways. Finally, we discuss the putative origins of SST cell deficits, as informed by recent research, and implications for therapeutic approaches. We conclude that deficits in SST interneurons represent a contributing cellular pathology and therefore a promising target for normalizing altered inhibitory function in MDD and other disorders with reduced SST cell and GABA functions. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  12. Topography of somatostatin gene expression relative to molecular progenitor domains during ontogeny of the mouse hypothalamus

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    Nicanor eMorales-Delgado

    2011-02-01

    Full Text Available The hypothalamus comprises alar, basal and floor plate developmental compartments. Recent molecular data support a rostro-caudal subdivision into rostral (terminal and caudal (peduncular halves. In this context, the distribution of neuronal populations expressing somatostatin (Sst mRNA was analyzed in the developing mouse hypothalamus, comparing with the expression pattern of the genes Orthopedia (Otp, Distal-less 5 (Dlx5, Sonic Hedgehog (Shh and Nk2 homeobox 1 (Nkx2.1. At embryonic day 10.5 (E10.5, Sst mRNA was first detectable in the anterobasal nucleus, a Nkx2.1-, Shh- and Otp- positive basal domain. By E13.5, nascent Sst expression was also related to two additional Otp-positive domains within the alar plate and one in the basal plate. In the alar plate, Sst-positive cells were observed in rostral and caudal ventral subdomains of the Otp-positive paraventricular complex. An additional basal Sst-expressing cell group was found within a longitudinal Otp-positive periretromamillary band that separates the retromamillary area from tuberal areas. Apart of subsequent growth of these initial populations, at E13.5 and E15.5 some Sst-positive derivatives migrate tangentially into neighboring regions. A subset of cells produced at the anterobasal nucleus disperses ventralwards into the shell of the ventromedial hypothalamic nucleus and the arcuate nucleus. Cells from the rostroventral paraventricular subdomain reach the suboptic nucleus, whereas a caudal contingent migrates radially into lateral paraventricular, perifornical and entopeduncular nuclei. Our data provide a topologic map of molecularly-defined progenitor areas originating a specific neuron type during early hypothalamic development. Identification of four main separate sources helps to understand causally its complex adult organization.

  13. Effects of the neuroprotective drugs somatostatin and brimonidine on retinal cell models of diabetic retinopathy.

    Science.gov (United States)

    Beltramo, Elena; Lopatina, Tatiana; Mazzeo, Aurora; Arroba, Ana I; Valverde, Angela M; Hernández, Cristina; Simó, Rafael; Porta, Massimo

    2016-12-01

    Diabetic retinopathy is considered a microvascular disease, but recent evidence has underlined early involvement of the neuroretina with interactions between microvascular and neural alterations. Topical administration of somatostatin (SST), a neuroprotective molecule with antiangiogenic properties, prevents diabetes-induced retinal neurodegeneration in animals. The α 2 -adrenergic receptor agonist brimonidine (BRM) decreases vitreoretinal vascular endothelial growth factor and inhibits blood-retinal barrier breakdown in diabetic rats. However, SST and BRM effects on microvascular cells have not yet been studied. We investigated the behaviour of these drugs on the crosstalk between microvasculature and neuroretina. Expression of SST receptors 1-5 in human retinal pericytes (HRP) was checked. We subsequently evaluated the effects of diabetic-like conditions (high glucose and/or hypoxia) with/without SST/BRM on HRP survival. Endothelial cells (EC) and photoreceptors were maintained in the above conditions and their conditioned media (CM) used to culture HRP. Vice versa, HRP-CM was used on EC and photoreceptors. Survival parameters were assessed. HRP express the SST receptor 1 (SSTR1). Glucose fluctuations mimicking those occurring in diabetic subjects are more damaging for pericytes and photoreceptors than stable high glucose and hypoxic conditions. SST/BRM added to HRP in diabetic-like conditions decrease EC apoptosis. However, neither SST nor BRM changed the response of pericytes and neuroretina-vascular crosstalk under diabetic-like conditions. Retinal pericytes express SSTR1, indicating that they can be a target for SST. Exposure to SST/BRM had no adverse effects, direct or mediated by the neuroretina, suggesting that these molecules could be safely evaluated for the treatment of ocular diseases.

  14. Preliminary research on relationship between the somatostatin level and diabetes mellitus

    International Nuclear Information System (INIS)

    Shi Hongzhen; Wang Zizheng; Du Tongxin; Liu Jiaqin; Wei Jin; Qi Shaokang

    1996-01-01

    To study the relationship between somatostatin (SS) and diabetes mellitus (DM), and also among SS, C-peptide (C-P), insulin (INS), and glucagon (Gluc). Fasting and postprandial 2h plasma SS, INS, C-P and Gluc in 17 patients of IDDM, 22 patients of NIDDM and 23 normal controls were detected simultaneously by RIA. Dynamic assessment of above parameters was performed at 0,30,60,120,180 min in 8 cases of NIDDM with oral glucose tolerance test (OGTT). Fasting and postprandial 2h SS and Gluc levels were significantly higher in DM than in normal controls. The ratios of SS/INS and Gluc/SS in IDDM were higher than those in NIDDM and normal controls, while no difference was found in NIDDM and normal controls. Fasting Gluc/SS was similar in three groups, but increased significantly in DM after oral glucose intake and postprandial state. OGTT found that the levels of SS both in patients of nIDDM and normal controls reached its maximum at 30 min with a smaller amplitude in peak value in patient group, while the levels of INS, C-P and Gluc attained its climax at 60 min, lagging behind the normal controls (30 min), with a sustained high levels at 180 min. There was a difference of SS-secreting phase between DM and normal controls. The ratios of SS/INS, Gluc/INS provided an important reference value for diagnosis of DM. A relative insufficiency of SS secretion and Gluc/SS imbalance under glucose-loading may play an important role in the etiology of DM

  15. SPECT/CT with radiolabeled somatostatin analogues in the evaluation of systemic granulomatous infections

    Energy Technology Data Exchange (ETDEWEB)

    Monteiro, Paulo Henrique Silva; Souza, Thiago Ferreira de; Moretti, Maria Luiza; Resende, Mariangela Ribeiro; Lima, Mariana da Cunha Lopes de; Santos, Allan Oliveira; Ramos, Celso Darío, E-mail: paulohsm42@gmail.com [Universidade de Campinas (UNICAMP), SP (Brazil). Escola de Medicina; Mengatti Jair [Instituto de Pesquisas Energéticas e Nucleares (IPEN/CNEN-SP), São Paulo, SP (Brazil)

    2017-11-15

    Objective: To evaluate SPECT/CT with radiolabeled somatostatin analogues (RSAs) in systemic granulomatous infections in comparison with gallium-67 ({sup 67}Ga) citrate scintigraphy. Materials And Methods: We studied 28 patients with active systemic granulomatous infections, including tuberculosis, paracoccidioidomycosis, pneumocystosis, cryptococcosis, aspergillosis, leishmaniasis, infectious vasculitis, and an unspecified opportunistic infection. Of the 28 patients, 23 had started specific treatment before the study outset. All patients underwent whole-body SPECT/CT imaging: 7 after injection of {sup 99m}Tc-EDDA-HYNIC-TOC, and 21 after injection of {sup 111}In-DTPA-octreotide. All patients also underwent {sup 67}Ga citrate imaging, except for one patient who died before the {sup 67}Ga was available. Results: In 20 of the 27 patients who underwent imaging with both tracers, 27 sites of active disease were detected by {sup 67}Ga citrate imaging and by SPECT/CT with an RSA. Both tracers had negative results in the other 7 patients. RSA uptake was visually lower than {sup 67}Ga uptake in 11 of the 20 patients with positive images and similar to {sup 67}Ga uptake in the other 9 patients. The only patient who did not undergo {sup 67}Ga scintigraphy underwent {sup 99m}Tc-EDDA-HYNIC-TOC SPECT/CT-guided biopsy of a lung cavity with focal RSA uptake, which turned to be positive for aspergillosis. Conclusion: SPECT/CT with {sup 99m}Tc-EDDA-HYNIC-TOC or {sup 111}In-DTPA-octreotide seems to be a good alternative to {sup 67}Ga citrate imaging for the evaluation of patients with systemic granulomatous disease. (author)

  16. Somatostatin receptor scintigraphy to predict the clinical evolution and therapeutic response of thyroid-associated ophthalmopathy

    Energy Technology Data Exchange (ETDEWEB)

    Nocaudie, M.; Bailliez, A.; Itti, E. [Centre Hospitalier Regional et Universitaire, Lille (France). Service Central de Medecine Nucleaire et Imagerie Fonctionnelle; Bauters, C.; Wemeau, J.L. [Clinique d`Endocrinologie, Centre Hospitalier Regional et Universitaire de Lille (France); Marchandise, X.

    1999-05-01

    Management of thyroid-associated ophthalmopathy remains a topic of controversy. Immunosuppressive treatments have to be applied at peak disease activity and before criteria of severity develop. Expression of somatostatin receptors on activated lymphocytes allows scintigraphic imaging with indium-111 pentetreotide. We conducted a prospective study with 17 patients who presented severe ophthalmopathy (11 Graves` disease, four Hashimoto`s thyroiditis, two isolated in appearance: Means` syndrome). Each patient underwent hormonal (free T{sub 3} and TSH) and immunological (TBII) assessment, an orbital computed tomography scan or magnetic resonance imaging, a visual functional examination and {sup 111}In-pentetreotide orbital scintigraphy before undergoing treatment by steroids and/or radiotherapy, independently of scintigraphic results. At 4 and 24 h after the intravenous injection of 111 MBq of {sup 111}In-pentetreotide, planar imaging centred on the head and neck (anterior and both lateral views) was carried out. Retrobulbar uptake was assessed by visual semi-quantitative analysis (score given by two independent trained observers) and by quantitative analyses (regions of interest, orbit/brain uptake indices). Patients were ophthalmologically followed up for 6 months and then classified as improved or not. Visual semi-quantitative analysis of 4-h/24-h planar images was correlated with the ophthalmological evolution ({chi}{sup 2} test, P<0.01). All ten patients in whom scintigraphy was considered positive were clinically improved at 6 months, and of the seven patients in whom scintigraphy was negative, six were not improved. Nevertheless, objective quantitative analysis did not succeed in confirming these results. We conclude that {sup 111}In-pentetreotide scintigraphy requires further developments, including quantitative single-photon emission tomographic acquisition, if its role as a guide to therapeutic strategy in thyroid-associated ophthalmopathy is to be confirmed

  17. Iodine-131 labelled octreotide: not an option for somatostatin receptor therapy

    International Nuclear Information System (INIS)

    Bakker, W.H.; Breeman, W.A.P.; Pluijm, M.E. van der; Jong, M. de; Visser, T.J.; Krenning, E.P.

    1996-01-01

    This study deals with the radioiodination of very small amounts of peptide on a therapeutic scale, the required purification procedures after radioiodination, and the influence of high beta fluxes from 131 I on a peptide during radioiodination and purification. Based on the regularly used therapeutic doses of 131 I in cancer treatment and out previous experience with [ 111 In-DTPA-D-Phe 1 ]-octreotide, it was assumed that a minimal effective therapeutic dose of 3.7 GBq 131 I has to be coupled to a maximum of ∼100 μg peptide, representing only a slight excess of peptide over 131 I. This contrasts with non-peptide radiopharmaceuticals in which high compound to radionuclide ratios are usually used. Labelling at low peptide to radionuclide ratios (low labelling yields) results in the formation of di-iodinated compounds, whereas at high peptide to radionuclide ratios mono-iodinated products of low specific activity are formed. Thus, after radioiodination the desired mono-iodinated peptide has to be separated form unreacted iodide, and from di-iodinated and unreacted peptide, as both compounds compete for the receptors. Possible radiolysis of the peptide during labelling and separation steps were investigated by irradiating 30 μg unlabelled peptide with 370 MBq 131 I in a small volume. The peptide composition of the incubation mixtures was investigated by high-performance liquid chromatography after irradiation for 30 min to 24 h. The results showed that the peptide was degraded with a half-life of less than 1 h. During the preparation of a real therapeutic dose (at much higher β-flux) the peptide will be degraded even faster during the various steps required. In conclusion, intact mono-iodinated 131 I-labelled somatostatin analogues for peptide receptor therapy will be difficult to obtain. (orig./VHE)

  18. Crosstalks between kisspeptin neurons and somatostatin neurons are not photoperiod dependent in the ewe hypothalamus.

    Science.gov (United States)

    Dufourny, Laurence; Lomet, Didier

    2017-12-01

    Seasonal reproduction is under the control of gonadal steroid feedback, itself synchronized by day-length or photoperiod. As steroid action on GnRH neurons is mostly indirect and therefore exerted through interneurons, we looked for neuroanatomical interactions between kisspeptin (KP) neurons and somatostatin (SOM) neurons, two populations targeted by sex steroids, in three diencephalic areas involved in the central control of ovulation and/or sexual behavior: the arcuate nucleus (ARC), the preoptic area (POA) and the ventrolateral part of the ventromedial hypothalamus (VMHvl). KP is the most potent secretagogue of GnRH secretion while SOM has been shown to centrally inhibit LH pulsatile release. Notably, hypothalamic contents of these two neuropeptides vary with photoperiod in specific seasonal species. Our hypothesis is that SOM inhibits KP neuron activity and therefore indirectly modulate GnRH release and that this effect may be seasonally regulated. We used sections from ovariectomized estradiol-replaced ewes killed after photoperiodic treatment mimicking breeding or anestrus season. We performed triple immunofluorescent labeling to simultaneously detect KP, SOM and synapsin, a marker for synaptic vesicles. Sections from the POA and from the mediobasal hypothalamus were examined using a confocal microscope. Randomly selected KP or SOM neurons were observed in the POA and ARC. SOM neurons were also observed in the VMHvl. In both the ARC and POA, nearly all KP neurons presented numerous SOM contacts. SOM neurons presented KP terminals more frequently in the ARC than in the POA and VMHvl. Quantitative analysis failed to demonstrate major seasonal variations of KP and SOM interactions. Our data suggest a possible inhibitory action of SOM on all KP neurons in both photoperiodic statuses. On the other hand, the physiological significance of KP modulation of SOM neuron activity and vice versa remain to be determined. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Diversity and overlap of Parvalbumin and Somatostatin expressing interneurons in mouse presubiculum

    Directory of Open Access Journals (Sweden)

    Mérie eNassar

    2015-05-01

    Full Text Available The presubiculum, located between hippocampus and entorhinal cortex, plays a fundamental role in representing spatial information, notably head direction. Little is known about GABAergic interneurons of this region. Here, we used three transgenic mouse lines, Pvalb-Cre, Sst-Cre and X98, to examine distinct interneurons labeled with tdTomato or green fluorescent protein. The distribution of interneurons in presubicular lamina for each animal line was compared to that in the GAD67-GFP knock-in animal line. Labelling was specific in the Pvalb-Cre line with 87% of labeled interneurons immunopositive for (PV. Immunostaining for somatostatin (SOM revealed good specificity in the X98 line with 89% of fluorescent cells, but a lesser specificity in Sst-Cre animals where only 71% of labeled cells were immunopositive. A minority of ~ 6% of interneurons co-expressed PV and SOM in the presubiculum of Sst-Cre animals. The electrophysiological and morphological properties of fluorescent interneurons from Pvalb-Cre, Sst-Cre and X98 mice differed. Distinct physiological groups of presubicular interneurons were resolved by unsupervised cluster analysis of parameters describing passive properties, firing patterns and AP shapes. One group consisted of SOM-positive, Martinotti type neurons with a low firing threshold (cluster 1. Fast spiking basket cells, mainly from the Pvalb-Cre line, formed a distinct group (cluster 3. Another group (cluster 2 contained interneurons of intermediate electrical properties and basket-cell like morphologies. These labeled neurons were recorded from both Sst-Cre and Pvalb-Cre animals. Thus, our results reveal a wide variation in anatomical and physiological properties for these interneurons, a real overlap of interneurons immuno-positive for both PV and SOM as well as an off-target recombination in the Sst-Cre line, possibly linked to maternal cre inheritance.

  20. Automatic activation of categorical and abstract analogical relations in analogical reasoning.

    Science.gov (United States)

    Green, Adam E; Fugelsang, Jonathan A; Dunbar, Kevin N

    2006-10-01

    We examined activation of concepts during analogical reasoning. Subjects made either analogical judgments or categorical judgments about four-word sets. After each four-word set, they named the ink color of a single word in a modified Stroop task. Words that referred to category relations were primed (as indicated by longer response times on Stroop color naming) subsequent to analogical judgments and categorical judgments. This finding suggests that activation of category concepts plays a fundamental role in analogical thinking. When colored words referred to analogical relations, priming occurred subsequent to analogical judgments, but not to categorical judgments, even though identical four-word stimuli were used for both types of judgments. This finding lends empirical support to the hypothesis that, when people comprehend the analogy between two items, they activate an abstract analogical relation that is distinct from the specific content items that compose the analogy.

  1. Metamaterials for light rays: ray optics without wave-optical analog in the ray-optics limit

    International Nuclear Information System (INIS)

    Hamilton, Alasdair C; Courtial, Johannes

    2009-01-01

    Volumes of sub-wavelength electromagnetic elements can act like homogeneous materials: metamaterials. In analogy, sheets of optical elements such as prisms can act ray-optically like homogeneous sheet materials. In this sense, such sheets can be considered to be metamaterials for light rays (METATOYs). METATOYs realize new and unusual transformations of the directions of transmitted light rays. We study here, in the ray-optics and scalar-wave limits, the wave-optical analog of such transformations, and we show that such an analog does not always exist. Perhaps, this is the reason why many of the ray-optical possibilities offered by METATOYs have never before been considered.

  2. Age-related changes in Serum Growth Hormone, Insulin-like Growth Factor-1 and Somatostatin in System Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Malemud Charles J

    2004-10-01

    Full Text Available Abstract Background Systemic lupus erythematosus is an age- and gender-associated autoimmune disorder. Previous studies suggested that defects in the hypothalamic/pituitary axis contributed to systemic lupus erythematosus disease progression which could also involve growth hormone, insulin-like growth factor-1 and somatostatin function. This study was designed to compare basal serum growth hormone, insulin-like growth factor-1 and somatostatin levels in female systemic lupus erythematosus patients to a group of normal female subjects. Methods Basal serum growth hormone, insulin-like growth factor-1 and somatostatin levels were measured by standard radioimmunoassay. Results Serum growth hormone levels failed to correlate with age (r2 = 3.03 in the entire group of normal subjects (i.e. 20 – 80 years. In contrast, serum insulin-like growth factor-1 levels were inversely correlated with age (adjusted r2 = 0.092. Of note, serum growth hormone was positively correlated with age (adjusted r2 = 0.269 in the 20 – 46 year range which overlapped with the age range of patients in the systemic lupus erythematosus group. In that regard, serum growth hormone levels were not significantly higher compared to either the entire group of normal subjects (20 – 80 yrs or to normal subjects age-matched to the systemic lupus erythematosus patients. Serum insulin-like growth factor-1 levels were significantly elevated (p 55 yrs systemic lupus erythematosus patients. Conclusions These results indicated that systemic lupus erythematosus was not characterized by a modulation of the growth hormone/insulin-like growth factor-1 paracrine axis when serum samples from systemic lupus erythematosus patients were compared to age- matched normal female subjects. These results in systemic lupus erythematosus differ from those previously reported in other musculoskeletal disorders such as rheumatoid arthritis, osteoarthritis, fibromyalgia, diffuse idiopathic skeletal

  3. Somatostatin receptor positron emission tomography/computed tomography (PET/CT) in the evaluation of opsoclonus-myoclonus ataxia syndrome

    International Nuclear Information System (INIS)

    Joshi, Prathamesh; Lele, Vikram

    2013-01-01

    Opsoclonus-myoclonus ataxia (OMA) syndrome is the most common paraneoplastic neurological syndrome of childhood, associated with occult neuroblastoma in 20%-50% of all cases. OMA is the initial presentation of neuroblastoma in 1%-3% of children. Conventional radiological imaging approaches include chest radiography and abdominal computed tomography (CT). Nuclear medicine techniques, in form of 123 I/ 131 I-metaiodobenzylguanidine (MIBG) scintigraphy have been incorporated in various diagnostic algorithms for evaluation of OMA. We describe use of somatostatin receptor PET/CT with 68 Gallium- DOTA-DPhe 1 , Tyr 3 -octreotate (DOTATATE) in diagnosis of neuroblastoma in two cases of OMA

  4. Somatostatin receptor positron emission tomography/computed tomography (PET/CT) in the evaluation of opsoclonus-myoclonus ataxia syndrome.

    Science.gov (United States)

    Joshi, Prathamesh; Lele, Vikram

    2013-04-01

    Opsoclonus-myoclonus ataxia (OMA) syndrome is the most common paraneoplastic neurological syndrome of childhood, associated with occult neuroblastoma in 20%-50% of all cases. OMA is the initial presentation of neuroblastoma in 1%-3% of children. Conventional radiological imaging approaches include chest radiography and abdominal computed tomography (CT). Nuclear medicine techniques, in form of (123)I/(131)I-metaiodobenzylguanidine (MIBG) scintigraphy have been incorporated in various diagnostic algorithms for evaluation of OMA. We describe use of somatostatin receptor PET/CT with (68)Gallium- DOTA-DPhe(1), Tyr(3)-octreotate (DOTATATE) in diagnosis of neuroblastoma in two cases of OMA.

  5. The Young Solar Analogs Project

    Science.gov (United States)

    Gray, Richard O.; Saken, J. M.; Corbally, C. J.; Fuller, V.; Kahvaz, Y.; Lambert, R.; Newsome, I.; Seeds, M.

    2013-01-01

    We are carrying out a long-term project of measuring chromospheric activity and brightness variations in 31 young solar analogs (YSAs) using facilities at the Dark Sky Observatory (DSO - Appalachian State University) and the Vatican Advanced Technology Telescope (VATT). These YSAs are solar-type (spectral types F8 - K2) stars with ages ranging from 0.3 - 1.5 Gyr. The goal of this project is to gain better understanding of the magnetic activity of the early Sun, and especially how that activity may have impacted the development of life on the Earth. This project will also yield insights into the space environments experienced by young Earth analogs. We are currently in the 6th year of spectroscopic measurements of these stars: these data include Ca II H & K chromospheric flux measurements, and narrow-band measurements in the photospheric G-band, both obtained with the G/M spectrograph on the DSO 32-inch telescope. We will present evidence of activity cycles in a number of our stars, as well as periods determined from rotational modulation of the spectroscopic indices. The relationship between the Ca II activity index and the G-band index will be explored. NSF support for our project has provided funds for the construction of a robotic photometric telescope to monitor the program stars in a 5-passband system (Strömgren-v, Johnson-Cousins B, V, and R, and a 3-nm wide Hα filter). The robotic telescope has been functional since April 2012 and observes the program stars on every clear night; combined with the Piggy-back telescope attached to the DSO 32-inch, we now have photometric observations on over 130 nights stretching over nearly 2 years. We will examine the relationships between variations in the Ca II H & K index, the G-band index and the photometric bands. This project is supported by the National Science Foundation, grant AST-1109158.

  6. The Young Solar Analogs Project

    Science.gov (United States)

    Gray, Richard O.; Saken, J. M.; Corbally, C. J.; Seeds, M. F.; Morrison, S. S.

    2012-01-01

    We are carrying out a long-term project of measuring chromospheric activity and brightness variations in 31 young solar analogs (YSAs) using the Dark Sky Observatory (DSO -- Appalachian State University) 32-inch telescope and the G/M spectrograph. These YSAs are solar-type (spectral types F8 - K2) stars with ages ranging from 0.3 - 1.5 Gyr. The goal of this project is to gain better understanding of the magnetic activity of the early Sun, and especially how that activity may have impacted the development of life on the Earth. This project will also yield insights into the space environments experienced by young Earth analogs. We are currently in our 5th year of obtaining Ca II K & H chromospheric flux measurements, and are beginning to see signs of long-term activity cycles in a number of our stars. In addition, rotational modulation of the chromospheric fluxes is detectable in our data, and we have determined rotational periods for many of our stars. Short timescale increases in the K & H fluxes have been observed in a number of our stars; these events may be related to stellar flares. VATTSpec, a new moderate-resolution spectrograph on the 1.8-m Vatican Telescope in Arizona, has recently become involved with the project. This spectrograph will increase our ability to detect short-term changes in stellar activity on timescales of hours to minutes. We have been monitoring the program stars for one year in a multi-band photometric system consisting of Stromgren-v, and Johnson B, V, and R filters. We will soon add a narrow-band H-alpha filter to the system. Photometry is being carried out with a small piggy-back telescope on the 32-inch, but a robotic photometric telescope is currently being installed at DSO for this purpose. This project is supported by the National Science Foundation.

  7. Genetic activation, inactivation and deletion reveal a limited and nuanced role for somatostatin-containing basal forebrain neurons in behavioral state control.

    Science.gov (United States)

    Anaclet, Christelle; De Luca, Roberto; Venner, Anne; Malyshevskaya, Olga; Lazarus, Michael; Arrigoni, Elda; Fuller, Patrick M

    2018-05-07

    Recent studies have identified an especially important role for basal forebrain GABAergic (BF VGAT ) neurons in the regulation of behavioral waking and fast cortical rhythms associated with cognition. However, BF VGAT neurons comprise several neurochemically and anatomically distinct sub-populations, including parvalbumin- and somatostatin-containing BF VGAT neurons (BF Parv and BF SOM ), and it was recently reported that optogenetic activation of BF SOM neurons increases the probability of a wakefulness to non-rapid-eye movement (NREM) sleep transition when stimulated during the animal's rest period. This finding was unexpected given that most BF SOM neurons are not NREM sleep active and that central administration of the synthetic SOM analog, octreotide, suppresses NREM sleep or increases REM sleep. Here we employed a combination of genetically-driven chemogenetic and optogenetic activation, chemogenetic inhibition and ablation approaches to further explore the in vivo role of BF SOM neurons in arousal control. Our findings indicate that acute activation or inhibition of BF SOM neurons is neither wakefulness- nor NREM sleep-promoting, is without significant effect on the EEG, and that chronic loss of these neurons is without effect on total 24h sleep amounts, although a small but significant increase in waking was observed in the lesioned mice during the early active period. Our in vitro cell recordings further reveal electrophysiological heterogeneity in BF SOM neurons, specifically suggesting at least two distinct sub-populations. Taken together our data support the more nuanced view that BF SOM are electrically heterogeneous and are not NREM sleep- or wake-promoting per se , but may exert, in particular during the early active period, a modest inhibitory influence on arousal circuitry. SIGNIFICANCE STATEMENT The cellular basal forebrain (BF) is a highly complex area of the brain that is implicated in a wide-range of higher-level neurobiological processes

  8. Proghrelin-derived peptides influence the secretion of insulin, glucagon, pancreatic polypeptide and somatostatin: a study on isolated islets from mouse and rat pancreas

    DEFF Research Database (Denmark)

    Qader, S.S.; Hakanson, R.; Lundquist, I.

    2008-01-01

    ghrelin, and to the 23-amino acid peptide obestatin, claimed to be a physiological opponent of acyl ghrelin. This study examines the effects of the proghrelin products, alone and in combinations, on the secretion of insulin, glucagon, pancreatic polypeptide (PP) and somatostatin from isolated islets...... times higher concentration than acyl ghrelin (corresponding to the ratio of the two peptides in circulation), desacyl ghrelin abolished the effects of acyl ghrelin but not those of obestatin. Acyl ghrelin and obestatin affected the secretion of glucagon, PP and somatostatin at physiologically relevant...

  9. Priming analogical reasoning with false memories.

    Science.gov (United States)

    Howe, Mark L; Garner, Sarah R; Threadgold, Emma; Ball, Linden J

    2015-08-01

    Like true memories, false memories are capable of priming answers to insight-based problems. Recent research has attempted to extend this paradigm to more advanced problem-solving tasks, including those involving verbal analogical reasoning. However, these experiments are constrained inasmuch as problem solutions could be generated via spreading activation mechanisms (much like false memories themselves) rather than using complex reasoning processes. In three experiments we examined false memory priming of complex analogical reasoning tasks in the absence of simple semantic associations. In Experiment 1, we demonstrated the robustness of false memory priming in analogical reasoning when backward associative strength among the problem terms was eliminated. In Experiments 2a and 2b, we extended these findings by demonstrating priming on newly created homonym analogies that can only be solved by inhibiting semantic associations within the analogy. Overall, the findings of the present experiments provide evidence that the efficacy of false memory priming extends to complex analogical reasoning problems.

  10. Neural correlates of creativity in analogical reasoning.

    Science.gov (United States)

    Green, Adam E; Kraemer, David J M; Fugelsang, Jonathan A; Gray, Jeremy R; Dunbar, Kevin N

    2012-03-01

    Brain-based evidence has implicated the frontal pole of the brain as important for analogical mapping. Separately, cognitive research has identified semantic distance as a key determinant of the creativity of analogical mapping (i.e., more distant analogies are generally more creative). Here, we used functional magnetic resonance imaging to assess brain activity during an analogy generation task in which we varied the semantic distance of analogical mapping (as derived quantitatively from a latent semantic analysis). Data indicated that activity within an a priori region of interest in left frontopolar cortex covaried parametrically with increasing semantic distance, even after removing effects of task difficulty. Results implicate increased recruitment of frontopolar cortex as a mechanism for integrating semantically distant information to generate solutions in creative analogical reasoning. 2012 APA, all rights reserved

  11. An emergent approach to analogical inference

    Science.gov (United States)

    Thibodeau, Paul H.; Flusberg, Stephen J.; Glick, Jeremy J.; Sternberg, Daniel A.

    2013-03-01

    In recent years, a growing number of researchers have proposed that analogy is a core component of human cognition. According to the dominant theoretical viewpoint, analogical reasoning requires a specific suite of cognitive machinery, including explicitly coded symbolic representations and a mapping or binding mechanism that operates over these representations. Here we offer an alternative approach: we find that analogical inference can emerge naturally and spontaneously from a relatively simple, error-driven learning mechanism without the need to posit any additional analogy-specific machinery. The results also parallel findings from the developmental literature on analogy, demonstrating a shift from an initial reliance on surface feature similarity to the use of relational similarity later in training. Variants of the model allow us to consider and rule out alternative accounts of its performance. We conclude by discussing how these findings can potentially refine our understanding of the processes that are required to perform analogical inference.

  12. Analog techniques in CEBAF's RF control system

    International Nuclear Information System (INIS)

    Hovater, C.; Fugitt, J.

    1989-01-01

    Recent developments in high-speed analog technology have progressed into the areas of traditional RF technology. Diode related devices are being replaced by analog IC's in the CEBAF RF control system. Complex phase modulators and attenuators have been successfully tested at 70 MHz. They have three advantages over existing technology: lower cost, less temperature sensitivity, and more linearity. RF signal conditioning components and how to implement the new analog IC's will be covered in this paper. 4 refs., 5 figs

  13. Analog techniques in CEBAF'S RF control system

    International Nuclear Information System (INIS)

    Hovater, C.; Fugitt, J.

    1989-01-01

    Recent developments in high-speed analog technology have progressed into the areas of traditional rf technology. Diode-related devices are being replaced by analog IC's in the CEBAF rf control system. Complex phase modulators and attenuators have been successfully tested at 70 MHz. They have three advantages over existing technology: lower cost, less temperature sensitivity, and more linearity. Rf signal conditioning components and how to implement the new analog IC's will be covered in this paper. 4 refs., 5 figs

  14. Design and Analysis of Reconfigurable Analog System

    Science.gov (United States)

    2011-02-01

    34010010" �" �" �" �" �" �" �±" N3 N2 N± P1 P2 P3 * Current sources $RR = 1; *Ramp Rate (slope of the...2008/12/12/31e83bac-500f-4182- acca -4d360295fd9c.pdf, Analog Devices, Analog Dialogue 39-06, June 2005. [15] D. A. Johns, K. Martin "Analog Integrated

  15. Fermilab accelerator control system: Analog monitoring facilities

    International Nuclear Information System (INIS)

    Seino, K.; Anderson, L.; Smedinghoff, J.

    1987-10-01

    Thousands of analog signals are monitored in different areas of the Fermilab accelerator complex. For general purposes, analog signals are sent over coaxial or twinaxial cables with varying lengths, collected at fan-in boxes and digitized with 12 bit multiplexed ADCs. For higher resolution requirements, analog signals are digitized at sources and are serially sent to the control system. This paper surveys ADC subsystems that are used with the accelerator control systems and discusses practical problems and solutions, and it describes how analog data are presented on the console system

  16. Relations as transformations: implications for analogical reasoning.

    Science.gov (United States)

    Leech, Robert; Mareschal, Denis; Cooper, Richard P

    2007-07-01

    We present two experiments assessing whether the size of a transformation instantiating a relation between two states of the world (e.g., shrinks) is a performance factor affecting analogical reasoning. The first experiment finds evidence of transformation size as a significant factor in adolescent analogical problem solving while the second experiment finds a similar effect on adult analogical reasoning using a markedly different analogical completion paradigm. The results are interpreted as providing evidence for the more general framework that cognitive representations of relations are best understood as mental transformations.

  17. Epistemology of analogy: Knowledge, society and expression

    Directory of Open Access Journals (Sweden)

    Mauricio Beuchot

    2017-06-01

    Full Text Available In this article we expose the bases of analog epistemology. This theory of knowledge is between an extreme subjectivism and an extreme objectivism. Analog hermeneutics is a realistic hermeneutics. She seeks the truth, but incorporates the meaning and emotion. We have separated the reason from the experience, the praxis theory, the mind or the soul of the body. We have to get them back together, if we do not get lost in the rational (which says little of the human being, or we lose ourselves in the emotional (without logical consistency. The analogical hermeneutic realism is able, thanks to the analogy itself, to mediate in this way of union.

  18. Expert analogy use in a naturalistic setting

    Science.gov (United States)

    Kretz, Donald R.; Krawczyk, Daniel C.

    2014-01-01

    The use of analogy is an important component of human cognition. The type of analogy we produce and communicate depends heavily on a number of factors, such as the setting, the level of domain expertise present, and the speaker's goal or intent. In this observational study, we recorded economics experts during scientific discussion and examined the categorical distance and structural depth of the analogies they produced. We also sought to characterize the purpose of the analogies that were generated. Our results supported previous conclusions about the infrequency of superficial similarity in subject-generated analogs, but also showed that distance and depth characteristics were more evenly balanced than in previous observational studies. This finding was likely due to the nature of the goals of the participants, as well as the broader nature of their expertise. An analysis of analogical purpose indicated that the generation of concrete source examples of more general target concepts was most prevalent. We also noted frequent instances of analogies intended to form visual images of source concepts. Other common purposes for analogies were the addition of colorful speech, inclusion (i.e., subsumption) of a target into a source concept, or differentiation between source and target concepts. We found no association between depth and either of the other two characteristics, but our findings suggest a relationship between purpose and distance; i.e., that visual imagery typically entailed an outside-domain source whereas exemplification was most frequently accomplished using within-domain analogies. Overall, we observed a rich and diverse set of spontaneously produced analogical comparisons. The high degree of expertise within the observed group along with the richly comparative nature of the economics discipline likely contributed to this analogical abundance. PMID:25505437

  19. Expert Analogy Use in a Naturalistic Setting

    Directory of Open Access Journals (Sweden)

    Donald R Kretz

    2014-11-01

    Full Text Available The use of analogy is an important component of human cognition. The type of analogy we produce and communicate depends heavily on a number of factors, such as the setting, the level of domain expertise present, and the speaker’s goal or intent. In this observational study, we recorded economics experts during scientific discussion and examined the categorical distance and structural depth of the analogies they produced. We also sought to characterize the purpose of the analogies that were generated. Our results supported previous conclusions about the infrequency of superficial similarity in subject-generated analogs, but also showed that distance and depth characteristics were more evenly balanced than in previous observational studies. This finding was likely due to the nature of the goals of the participants, as well as the broader nature of their expertise. An analysis of analogical purpose indicated that the generation of concrete source examples of more general target concepts was most prevalent. We also noted frequent instances of analogies intended to form visual images of source concepts. Other common purposes for analogies were the addition of colorful speech, inclusion (i.e., subsumption of a target into a source concept, or differentiation between source and target concepts. We found no association between depth and either of the other two characteristics, but our findings suggest a relationship between purpose and distance; i.e., that visual imagery typically entailed an outside-domain source whereas exemplification was most frequently accomplished using within-domain analogies. Overall, we observed a rich and diverse set of spontaneously produced analogical comparisons. The high degree of expertise within the observed group along with the richly comparative nature of the economics discipline likely contributed to this analogical abundance.

  20. NMDAR hypofunction and somatostatin-expressing GABAergic interneurons and receptors: A newly identified correlation and its effects in schizophrenia

    Directory of Open Access Journals (Sweden)

    Fatemah Alherz

    2017-06-01

    Full Text Available This review investigates the association between N-methyl-d-Aspartate receptor (NMDAR hypofunction and somatostatin-expressing GABAergic interneurons (SST+ and how it contributes to the cognitive deficits observed in schizophrenia (SZ. This is based on evidence that NMDAR antagonists caused symptoms resembling SZ in healthy individuals. NMDAR hypofunction in GABAergic interneurons results in the modulation of the cortical network oscillation, particularly in the gamma range (30–80 Hz. These gamma-band oscillation (GBO abnormalities were found to lead to the cognitive deficits observed in the disorder. Postmortem mRNA studies have shown that SST decreased more significantly than any other biomarker in schizophrenic subjects. The functional role of Somatostatin (SST in the aetiology of SZ can be studied through its receptors. Genetic knockout studies in animal models in Huntington's disease (HD have shown that a specific SST receptor, SSTR2, is increased along with the increased NMDAR activity, with opposing patterns observed in SZ. A direct correlation between SSTR and NMDAR is hence inferred in this review with the hope of finding a potential new therapeutic target for the treatment of SZ and related neurological conditions.

  1. Impact of the scintigraphy of somatostatin receptors upon the therapeutic strategy in patients bearing digestive endocrine tumors

    International Nuclear Information System (INIS)

    Lebtahi, R.; Cadiot, G.; Genin, R.; Delahaye, N.; Faraggi, M.; Daou, D.; Peker, C.; Migon, M.; Le Guludec, D.

    1997-01-01

    The scintigraphy of somatostatin receptors (SSR) is a sensible method for detecting the gastroenteric-pancreatic endocrine tumors and their metastases. The aim of this study is to evaluate the clinical impact of the results of SSR in taking patients in therapeutic charge. A hundred and sixty patients bearing biologically and/or histologically proved digestive endocrine tumors were prospectively studied. The patients were classified in 3 groups: group I - 90 patients with no known metastases; group II - 59 patients with liver metastases and group III - 11 patients with known extra-hepatic metastases. The results of the scintigraphy were compared with those of conventional imaging. The following results were obtained: in group 1 (90 patients) the conventional imaging has allowed detecting 53 primitive tumors in 44 patients. The SSR visualized 68% of these sites and has detected 26 supplementary primitive sites in 20 patients and 29 metastatic sites in 25 patients. In group II the scintigraphy has detected 95% of hepatic metastases and revealed 23 new metastasis sites and 18/59 patients. In group III the scintigraphy has detected 11 new sites in 7 patients. The results of scintigraphy modified the patient's classification in 38 cases (24%). The therapeutic strategy was modified for 40 patients (25%). In conclusion, the scintigraphy of somatostatin receptors is able to detect a significant number of digestive endocrine tumors what has important implications for therapeutical planning of the treatment of patients. It must be carried out during pre-therapeutic extension examination of these tumors

  2. Normal uptake of 68Ga-DOTA-TOC by the pancreas uncinate process mimicking malignancy at somatostatin receptor PET.

    Science.gov (United States)

    Jacobsson, Hans; Larsson, Patricia; Jonsson, Cathrine; Jussing, Emma; Grybäck, Per

    2012-04-01

    To characterize a commonly occurring increased uptake by the uncinate process of the pancreas at PET/CT using 68Ga-DOTA-d-Phe1-Tyr3-octreotide (68Ga-DOTA-TOC). This tracer has replaced In pentetreotide (OctreoScan®) for somatostatin receptor scintigraphy at our laboratory. Fifty of our first 74 PET/CT examinations with 68Ga-DOTA-TOC could be evaluated in retrospect. None of these patients had surgery or showed any pathology in the pancreas head at the concomitant CT. Thirty-five of the 50 examinations (70%) showed an uptake by the uncinate process sufficiently intense to be interpreted as pathologic and simulating a tumor. Mean SUVmax was 9.2. Mean SUVmean using an isoactivity cut-off of >75% and >50% was 7.8 and 6.0, respectively. Volume calculations of the uncinate process activity using these definitions gave 0.9 mL and 4.2 mL, respectively. There is a frequent physiological uptake of 68Ga-DOTA-TOC by the pancreas uncinate process. This may be caused by an accumulation of pancreatic polypeptide-containing cells expressing somatostatin receptors. If there is a normal finding at concomitant diagnostic CT, this uptake should be regarded as physiological.

  3. Alterations in Somatostatin Cells and Biochemical Parameters Following Zinc Supplementation in Gastrointestinal Tissue of St reptozotocin-Induced Diabetic Rats

    International Nuclear Information System (INIS)

    Bolkent, Sema; Bolkent, Sehnaz; Yanardag, Refiye; Mutlu, Ozgur; Yildirim, Sukriye

    2006-01-01

    Chronic hyperglycemia in diabetes is a major causative factor of free radical generation which further leads to many secondary diabetic complications via the damage to cellular proteins, membrane lipids, and nucleic acids. Zinc is an essential trace element in all living systems and plays a structural role in many proteins and enzymes. Somatostatin is known to have inhibitory effects on various gastrointestinal functions. Therefore, we determined somatostatin protein production and secretion levels, and biochemical and light microscopical changes following zinc supplementation in the gastrointestinal tract of streptozotocin (STZ)-diabetic rats. The animals were divided into four groups: Group I: control (untreated) animals; Group II: control animals given zinc sulfate; Group III: diabetic animals; and Group IV: diabetic animals given zinc sulfate. Zinc sulfate was given to the animals by gavage at a daily dose of 100 mg/kg body weight for 60 days. Diabetes was induced by intraperitoneal (i.p.) injection of STZ in a single dose of 65 mg/kg. For histological studies, stomach and duodenum tissues were fixed in Bouin solution and sections stained with Masson’s trichrome and Periodic-Acid-Schiff. Tissue homogenates were used for protein, lipid peroxidation (LPO), glutathione (GSH), and nonenzymatic glycosylation (NEG) analyses. Zinc supplementation to the STZ-diabetic rats revealed the protective effect of zinc on these parameters. Zinc supplementation may contribute to prevent at least some complications of diabetes mellitus

  4. Somatostatin and opioid receptors do not regulate proliferation or apoptosis of the human multiple myeloma U266 cells

    Directory of Open Access Journals (Sweden)

    Allouche Stéphane

    2009-06-01

    Full Text Available Abstract Background opioid and somatostatin receptors (SSTRs that can assemble as heterodimer were individually reported to modulate malignant cell proliferation and to favour apoptosis. Materials and methods: SSTRs and opioid receptors expression were examined by RT-PCR, western-blot and binding assays, cell proliferation was studied by XTT assay and propidium iodide (PI staining and apoptosis by annexin V-PI labelling. Results almost all human malignant haematological cell lines studied here expressed the five SSTRs. Further experiments were conducted on the human U266 multiple myeloma cells, which express also μ-opioid receptors (MOP-R. XTT assays and cell cycle studies provide no evidence for a significant effect upon opioid or somatostatin receptors stimulation. Furthermore, neither direct effect nor potentiation of the Fas-receptor pathway was detected on apoptosis after these treatments. Conclusion these data suggest that SSTRs or opioid receptors expression is not a guaranty for an anti-tumoral action in U266 cell line.

  5. δ-opioid receptor and somatostatin receptor-4 heterodimerization: possible implications in modulation of pain associated signaling.

    Directory of Open Access Journals (Sweden)

    Rishi K Somvanshi

    Full Text Available Pain relief is the principal action of opioids. Somatostatin (SST, a growth hormone inhibitory peptide is also known to alleviate pain even in cases when opioids fail. Recent studies have shown that mice are prone to sustained pain and devoid of analgesic effect in the absence of somatostatin receptor 4 (SSTR4. In the present study, using brain slices, cultured neurons and HEK-293 cells, we showed that SSTR4 and δ-Opioid receptor (δOR exist in a heteromeric complex and function in synergistic manner. SSTR4 and δOR co-expressed in cortical/striatal brain regions and spinal cord. Using cultured neuronal cells, we describe the heterogeneous complex formation of SSTR4 and δOR at neuronal cell body and processes. Cotransfected cells display inhibition of cAMP/PKA and co-activation of SSTR4 and δOR oppose receptor trafficking induced by individual receptor activation. Furthermore, downstream signaling pathways either associated with withdrawal or pain relief are modulated synergistically with a predominant role of SSTR4. Inhibition of cAMP/PKA and activation of ERK1/2 are the possible cellular adaptations to prevent withdrawal induced by chronic morphine use. Our results reveal direct intra-membrane interaction between SSTR4 and δOR and provide insights for the molecular mechanism for the anti-nociceptive property of SST in combination with opioids as a potential therapeutic approach to avoid undesirable withdrawal symptoms.

  6. Curatorial Acts

    NARCIS (Netherlands)

    Bal, M.

    2012-01-01

    In a self-critical inquiry into my own recent work of co-curating and the experience of seeing my video work being curated by others, this article examines acts of framing as performative acts that seek to transform visitors' preconceptions. This affective effect is pursued by means of immersion,

  7. Young Children's Analogical Reasoning in Science Domains

    Science.gov (United States)

    Haglund, Jesper; Jeppsson, Fredrik; Andersson, Johanna

    2012-01-01

    This exploratory study in a classroom setting investigates first graders' (age 7-8 years, N = 25) ability to perform analogical reasoning and create their own analogies for two irreversible natural phenomena: mixing and heat transfer. We found that the children who contributed actively to a full-class discussion were consistently successful at…

  8. Children's Use of Analogy during Collaborative Reasoning

    Science.gov (United States)

    Lin, Tzu-Jung; Anderson, Richard C.; Hummel, John E.; Jadallah, May; Miller, Brian W.; Nguyen-Jahiel, Kim; Morris, Joshua A.; Kuo, Li-Jen; Kim, Il-Hee; Wu, Xiaoying; Dong, Ting

    2012-01-01

    This microgenetic study examined social influences on children's development of analogical reasoning during peer-led small-group discussions of stories about controversial issues. A total of 277 analogies were identified among 7,215 child turns for speaking during 54 discussions from 18 discussion groups in 6 fourth-grade classrooms (N = 120; age…

  9. Patterns of Analogical Reasoning among Beginning Readers

    Science.gov (United States)

    Farrington-Flint, Lee; Wood, Clare; Canobi, Katherine H.; Faulkner, Dorothy

    2004-01-01

    Despite compelling evidence that analogy skills are available to beginning readers, few studies have actually explored the possibility of identifying individual differences in young children's analogy skills in early reading. The present study examined individual differences in children's use of orthographic and phonological relations between…

  10. ANALOGICAL REASONING USING TRANSFORMATIONS OF RULES

    OpenAIRE

    Haraguchi, Makoto; 原口, 誠

    1986-01-01

    A formalism of analogical reasoning is presented. The analogical reasoning can be considered as a deduction with a function of transforming logical rules. From this viewpoint, the reasoning is defined in terms of deduction, and is therefore realized in a logic programming system. The reasoning system is described as an extension of Prolog interpreter.

  11. Analogies in high school Brazilian chemistry textbooks

    Directory of Open Access Journals (Sweden)

    Rosária Justi

    2000-05-01

    Full Text Available This paper presents and discusses an analysis of the analogies presented by Brazilian chemistry textbooks for the medium level. The main aim of the analysis is to discuss whether such analogies can be said good teaching models. From the results, some aspects concerning with teachers' role are discussed. Finally, some new research questions are emphasised.

  12. Spectrometric analog-to-digital converter

    International Nuclear Information System (INIS)

    Ormandzhiev, S.I.; Jordanov, V.T.

    1988-01-01

    Converter of digit-by-digit counterbalancing with slipping dial with number of channels equal to total number of states of the main digital-to-analog converter of digit-by-digit counterbalancing systems is presented. Algorithm for selection of digital-to-analog converters, which must be used by means of computer is suggested

  13. An Analog Computer for Electronic Engineering Education

    Science.gov (United States)

    Fitch, A. L.; Iu, H. H. C.; Lu, D. D. C.

    2011-01-01

    This paper describes a compact analog computer and proposes its use in electronic engineering teaching laboratories to develop student understanding of applications in analog electronics, electronic components, engineering mathematics, control engineering, safe laboratory and workshop practices, circuit construction, testing, and maintenance. The…

  14. PEMETAAN ANALOGI PADA KONSEP ABSTRAK FISIKA

    Directory of Open Access Journals (Sweden)

    Nyoto Suseno

    2014-11-01

    Full Text Available The research of any where founded majority students have common difficulties in abstract physics concept. The result of observation, lecturers have problem  in teaching implementation of abstract concepts on physics learning. The objective of this research is to find out the ways how to overcome this problem. The research place of  physics education programs and senior high school. The data are colected by quetionere, observation and interview. The lecturer behavior to making out this case is use of analogy to make concrete a abstract concept. This action is true, because the analogies are dynamic tools that facilitate understanding, rather than representations of the correct and static explanations. Using analogies not only promoted profound understanding of abstract concept, but also helped students overcome their misconceptions. However used analogy in teaching not yet planed with seriousness, analogy used spontanously with the result that less optimal. By planing and selecting right analogy, the role of analogy can be achieved the optimal result. Therefore, it is important to maping analogies of abstract consepts on physics learning.

  15. Labelling and quality control of somatostatin analogues with 99mTc

    International Nuclear Information System (INIS)

    Verdera, S.; Balter, H.; Rodriguez, G.; Robles, A.; Oliver, P.; Laiz, J.; Souto, B.

    2001-01-01

    Techniques and methodologies for labelling peptides with 99m Tc and methods for their purification, chemical, radiochemical and biological controls were evaluated. With the purpose of gaining experience, labelling with 125 I was also studied. RC-160 was labelled with 125 I using iodogen as well as chloramine-T method. Higher yields were obtained with chloramine-T method (60%), rendering 125 I-peptide with 98% of radiochemical purity, with specific activity of 240 μCi/μg - 274 μCi/μg. The product was stable for five weeks (at -20 deg. C). For somatostatin receptors studies rat brain cortex membrane was prepared. Maximum binding capacity was 24.7% and Kaff for the binding of RC-160 to receptor was estimated as 2.0x10 10 M -1 . Other peptides as β-(2-Naphthyl)- D Ala-Cys-Tyr- D Trp-Lys-Val-Cys-Thr amide (N-9642, Σ) and mouse epidermal growth factor (mEGF) were also labelled by means of limiting chloramine-T method. In case of mEGF the availability of membrane receptors allowed us to experiment in mice as well as in vitro. The reaction yields were up to 60% and 70% respectively. Biodistribution of 125 I-mEGF in a mouse with adenoma demonstrated preferential uptake in tumour (21,7% injected dose). The radioimmunoassay system gave 39% maximum binding (MB) and 50% displacement (ED 50 ) for 10 ng/mL unlabelled mEGF. Direct method and BFC's for labelling peptides with 99m Tc were investigated and purification and quality controls studies were performed by TLC, HPLC (UV and gamma detection). RC-160 was labelled by a direct method using sodium dithionite as reducing agent with radiochemical purity >95%. The product was stable up to six hours (at RT). Considerable adsorption problems were observed. Biological behavior was in accordance with the compounds' lipophilicity. The synthesis of TOC conjugates with HYNIC as BFC was done with 45%±5% (n=3) yield. Labelling of HYNIC-TOC with tricine as co-ligand was conducted with up to 90% yield. Studies of RC-160 labelling using

  16. The influence of somatostatin receptor scintigraphy during preoperative staging of non-functioning pancreatic neuroendocrine tumours

    International Nuclear Information System (INIS)

    Jilesen, A.P.J.; Hoefnagel, S.J.M.; Busch, O.R.C.; Bennink, R.J.; Gouma, D.J.; Nieveen van Dijkum, E.J.M.

    2016-01-01

    Aim: To determine whether somatostatin receptor scintigraphy (SRS) influences the preoperative staging and clinical management of non-functioning pancreatic neuroendocrine tumours (NF-pNETs). Materials and methods: All SRS examinations performed between 2002–2013 were selected. Patients with NF-pNET were included if both computed tomography (CT) and SRS was performed during preoperative staging. The diagnostic accuracy of CT and SRS for detecting NF-pNET metastases was analysed. Altered TNM classification and changed clinical management were calculated. Changed management was defined as a change from surgical resection into systemic treatment or vice versa. NF-pNETs were defined as tumours without clinical symptoms of hormonal hypersecretion. Results: Overall, 62 patients with NF-pNET were included with a mean age of 57 years (SD: 12.4) 2 . In 28 patients (45%), CT and SRS were correct and in agreement in the detection of primary tumour/metastases. In 34 patients (55%), one of the techniques was incorrect and therefore, there was no agreement. SRS altered the TNM classification in 14 patients (23%) and clinical management in nine patients (15%). In patients without metastases on CT, SRS detected lymph node metastases in one patient. The sensitivity to detect the primary tumour with CT was 95% and with SRS was 73%. In detecting metastases, the sensitivity and specificity were both 85% for CT versus 80% and 90% for SRS. Conclusion: Overall, CT and SRS were in agreement in the detection of NF-pNET. In NF-pNET without suspicious metastatic lesions on CT, SRS has limited value. SRS may be indicated to confirm lesions suspicious for neuroendocrine tumours metastases. - Highlights: • In 28 patients (45%), CT and SRS were correct and in agreement in the detection of primary tumor/metastases. • In 34 patients (55%) one of the modalities was incorrect and therefore, there was no agreement. • Sensitivity to detect the primary tumor with CT and SRS were 95% versus 73

  17. SSTR-Mediated Imaging in Breast Cancer: Is There a Role for Radiolabeled Somatostatin Receptor Antagonists?

    Science.gov (United States)

    Dalm, Simone U; Haeck, Joost; Doeswijk, Gabriela N; de Blois, Erik; de Jong, Marion; van Deurzen, Carolien H M

    2017-10-01

    Recent studies have shown enhanced tumor targeting by novel somatostatin receptor (SSTR) antagonists compared with clinically widely used agonists. However, these results have been obtained mostly in neuroendocrine tumors, and only limited data are available for cancer types with lower SSTR expression, including breast cancer (BC). To date, two studies have reported higher binding of the antagonist than the agonist in BC, but in both studies only a limited number of cases were evaluated. In this preclinical study, we further investigated whether the application of an SSTR antagonist can improve SSTR-mediated BC imaging in a large panel of BC specimens. We also generated an in vivo BC mouse model and performed SPECT/MRI and biodistribution studies. Methods: Binding of 111 In-DOTA-Tyr 3 -octreotate (SSTR agonist) and 111 In-DOTA-JR11 (SSTR antagonist) to 40 human BC specimens was compared using in vitro autoradiography. SSTR2 immunostaining was performed to confirm SSTR2 expression of the tumor cells. Furthermore, binding of the radiolabeled SSTR agonist and antagonist was analyzed in tissue material from 6 patient-derived xenografts. One patient-derived xenograft, the estrogen receptor-positive model T126, was chosen to generate in vivo mouse models containing orthotopic breast tumors for in vivo SPECT/MRI and biodistribution studies after injection with 177 Lu-DOTA-Tyr 3 -octreotate or 177 Lu-DOTA-JR11. Results: 111 In-DOTA-JR11 binding to human BC tissue was significantly higher than 111 In-DOTA-Tyr 3 -octreotate binding ( P < 0.001). The median ratio of antagonist binding versus agonist binding was 3.39 (interquartile range, 2-5). SSTR2 immunostaining confirmed SSTR2 expression on the tumor cells. SPECT/MRI of the mouse model found better tumor visualization with the antagonist. This result was in line with the significantly higher tumor uptake of the radiolabeled antagonist than of the agonist as measured in biodistribution studies 285 min after radiotracer

  18. Computational approaches to analogical reasoning current trends

    CERN Document Server

    Richard, Gilles

    2014-01-01

    Analogical reasoning is known as a powerful mode for drawing plausible conclusions and solving problems. It has been the topic of a huge number of works by philosophers, anthropologists, linguists, psychologists, and computer scientists. As such, it has been early studied in artificial intelligence, with a particular renewal of interest in the last decade. The present volume provides a structured view of current research trends on computational approaches to analogical reasoning. It starts with an overview of the field, with an extensive bibliography. The 14 collected contributions cover a large scope of issues. First, the use of analogical proportions and analogies is explained and discussed in various natural language processing problems, as well as in automated deduction. Then, different formal frameworks for handling analogies are presented, dealing with case-based reasoning, heuristic-driven theory projection, commonsense reasoning about incomplete rule bases, logical proportions induced by similarity an...

  19. Structure problems in the analog computation

    International Nuclear Information System (INIS)

    Braffort, P.L.

    1957-01-01

    The recent mathematical development showed the importance of elementary structures (algebraic, topological, etc.) in abeyance under the great domains of classical analysis. Such structures in analog computation are put in evidence and possible development of applied mathematics are discussed. It also studied the topological structures of the standard representation of analog schemes such as additional triangles, integrators, phase inverters and functions generators. The analog method gives only the function of the variable: time, as results of its computations. But the course of computation, for systems including reactive circuits, introduces order structures which are called 'chronological'. Finally, it showed that the approximation methods of ordinary numerical and digital computation present the same structure as these analog computation. The structure analysis permits fruitful comparisons between the several domains of applied mathematics and suggests new important domains of application for analog method. (M.P.)

  20. Does somatostatin have a role in the regulation of cortisol secretion in primary pigmented nodular adrenocortical disease (PPNAD)? A clinical and in vitro investigation

    NARCIS (Netherlands)

    Z. Bram (Zakariae); P. Xekouki (Paraskevi); E. Louiset (Estelle); M. Keil (Mark); D. Avgeropoulos (Dimitrios); C. Giatzakis (Christoforos); M. Nesterova (Maria); N. Sinaii (Ninet); L.J. Hofland (Leo); R. Cherqaoui (Rabia); H. Lefebvre (Hervé); C.A. Stratakis (Constantine)

    2014-01-01

    textabstractContext: Somatostatin (SST) receptors (SSTRs) are expressed in a number of tissues, including the adrenal cortex, but their role in cortisol secretion has not been well characterized. Objectives: The objective of the study was to investigate the expression of SSTRs in the adrenal cortex

  1. Induction of Human Somatostatin Receptor Subtype 2 on Breast Tumors with an Adenoviral Vector for Their Treatment and Detection with a Radiolabeled Peptide

    National Research Council Canada - National Science Library

    Rogers, Buck

    2002-01-01

    .... An adenoviral vector encoding the human somatostatin receptor subtype 2 (AdSSTr2) has been produced. The MDA- MB-468 and BT-474 human breast cancer cells were infected with AdSSTr2 and harvested 48 h later for membrane preparations...

  2. Generating explanations via analogical comparison.

    Science.gov (United States)

    Hoyos, Christian; Gentner, Dedre

    2017-10-01

    Generating explanations can be highly effective in promoting learning in both adults and children. Our interest is in the mechanisms that underlie this effect and in whether and how they operate in early learning. In adult reasoning, explanation may call on many subprocesses-including comparison, counterfactual reasoning, and reasoning by exclusion; but it is unlikely that all these processes are available to young children. We propose that one process that may serve both children and adults is comparison. In this study, we asked whether children would use the results of a comparison experience when asked to explain why a model skyscraper was stable. We focused on a challenging principle-that diagonal cross-bracing lends stability to physical structures (Gentner et al., Cognitive Science, 40, 224-240, 2016). Six-year-olds either received no training or interacted with model skyscrapers in one of three different conditions, designed to vary in their potential to invite and support comparison. In the Single Model condition, children interacted with a single braced model. In the comparison conditions (Low Alignability and High Alignability), children compared braced and unbraced models. Following experience with the models, children were asked to explain why the braced model was stable. They then received two transfer tasks. We found that children who received highly alignable pairs were most likely to (a) produce brace-based explanations and (b) transfer the brace principle to a dissimilar context. This provides evidence that children can benefit from analogical comparison in generating explanations and also suggests limitations on this ability.

  3. ACT Test

    Science.gov (United States)

    ... to clot, the higher the degree of clotting inhibition. During surgery, the ACT is kept above a ... What is ECLS? An Introduction to Extracorporeal Life Support. University of Michigan Health System [On-line information]. ...

  4. The somatostatin receptor-targeted radiotherapeutic [90Y-DOTA-dPhe1,Tyr3]octreotide (90Y-SMT 487) eradicates experimental rat pancreatic CA 20948 tumours

    International Nuclear Information System (INIS)

    Stolz, B.; Weckbecker, G.; Smith-Jones, P.M.; Albert, R.; Raulf, F.; Bruns, C.

    1998-01-01

    Somatostatin receptor-expressing tumours are potential targets for therapy with radiolabelled somatostatin analogues. We have synthesized a number of such analogues in the past and identified [DOTA-dPhe 1 , Tyr 3 ]octreotide (SMT 487) as the most promising candidate molecule because of its advantageous properties in cellular and in vivo tumour models. In the current paper we describe the radiotherapeutic effect of yttrium-90 labelled SMT 487 in Lewis rats bearing the somatostatin receptor-positive rat pancreatic tumour CA 20948. SMT 487 binds with nanomolar affinity to both the human and the rat somatostatin receptor subtype 2 (sst 2 ) (human sst 2 IC 50 =0.9 nM, rat sst 2 IC 50 =0.5 nM). In vivo, 90 Y-SMT 487 distributed rapidly to the sst 2 expressing CA 20948 rat pancreatic tumour, with a tumour-to-blood ratio of 49.15 at 24 h post injection. A single intravenous administration of 10 mCi/kg 90 Y-SMT 487 resulted in a complete remission of the tumours in five out of seven CA 20948 tumour-bearing Lewis rats. No regrowth of the tumours occurred 8 months post injection. Control animals that were treated with 30 μg/kg of unlabelled SMT 487 had to be sacrificed 10 days post injection due to excessive growth or necrotic areas on the tumour surface. Upon re-inoculation of tumour cells into those rats that had shown complete remission, the tumours disappeared after 3-4 weeks of moderate growth without any further treatment. The present study shows for the first time the curative potential of 90 Y-SMT 487-based radiotherapy for somatostatin receptor-expressing tumours. Clinical phase I studies with yttrium-labelled SMT 487 have started in September 1997. (orig.)

  5. Frontopolar cortex mediates abstract integration in analogy.

    Science.gov (United States)

    Green, Adam E; Fugelsang, Jonathan A; Kraemer, David J M; Shamosh, Noah A; Dunbar, Kevin N

    2006-06-22

    Integration of abstractly similar relations during analogical reasoning was investigated using functional magnetic resonance imaging. Activation elicited by an analogical reasoning task that required both complex working memory and integration of abstractly similar relations was compared to activation elicited by a non-analogical task that required complex working memory in the absence of abstract relational integration. A left-sided region of the frontal pole of the brain (BA 9/10) was selectively active for the abstract relational integration component of analogical reasoning. Analogical reasoning also engaged a left-sided network of parieto-frontal regions. Activity in this network during analogical reasoning is hypothesized to reflect categorical alignment of individual component terms that make up analogies. This parieto-frontal network was also engaged by the complex control task, which involved explicit categorization, but not by a simpler control task, which did not involve categorization. We hypothesize that frontopolar cortex mediates abstract relational integration in complex reasoning while parieto-frontal regions mediate working memory processes, including manipulation of terms for the purpose of categorical alignment, that facilitate this integration.

  6. Advances in Analog Circuit Design 2015

    CERN Document Server

    Baschirotto, Andrea; Harpe, Pieter

    2016-01-01

    This book is based on the 18 tutorials presented during the 24th workshop on Advances in Analog Circuit Design. Expert designers present readers with information about a variety of topics at the frontier of analog circuit design, including low-power and energy-efficient analog electronics, with specific contributions focusing on the design of efficient sensor interfaces and low-power RF systems. This book serves as a valuable reference to the state-of-the-art, for anyone involved in analog circuit research and development. ·         Provides a state-of-the-art reference in analog circuit design, written by experts from industry and academia; ·         Presents material in a tutorial-based format; ·         Includes coverage of high-performance analog-to-digital and digital to analog converters, integrated circuit design in scaled technologies, and time-domain signal processing.

  7. The force of dissimilar analogies in bioethics.

    Science.gov (United States)

    Mertes, Heidi; Pennings, Guido

    2011-04-01

    Although analogical reasoning has long been a popular method of reasoning in bioethics, current literature does not sufficiently grasp its variety. We assert that the main shortcoming is the fact that an analogy's value is often judged on the extent of similarity between the source situation and the target situation, while in (bio)ethics, analogies are often used because of certain dissimilarities rather than in spite of them. We make a clear distinction between dissimilarities that aim to reinforce a similar approach in the source situation and the target situation and dissimilarities that aim to undermine or denounce a similar approach. The former kind of dissimilarity offers the analogy more normative force than if there were no dissimilarities present; this is often overlooked by authors who regard all relevant dissimilarities as detrimental to the analogy's strength. Another observation is that an evaluation of the normative force of an analogy cannot be made independently of moral principles or theories. Without these, one cannot select which elements in an analogy are morally relevant nor determine how they should be interpreted.

  8. Expression of somatostatin receptors subtype 2 and 5 in extraocular muscle tissue of hypothyroidism animal induced by 131I

    International Nuclear Information System (INIS)

    Li Fangdu; Chu Qiaomei; Xu Peikang; Yao Xiaohong; Shen Jiangfan

    2012-01-01

    Objective: To observe the expression and distribution of somatostatin receptors 2 and 5 (SSTR2, 5) in extraocular muscle in hypothyroidism and thyroid associated ophthalmopathy (TAO) Wister rats induced by 131 I. Methods: 20 Wister rats were randomly divided into experimental group and normal group(group D). According to 131 I doses of intraperitoneal injection, the experimental groups were divided into low (group A), middle (group B) and high dose group (group C). After 8 weeks, all rats were sacrificed and orbital tissue sections were applied to HE staining and Immunohistochemistry for the analysis of rat orbital tissue changes and SSTR2 and 5 distribution in extraocular muscle. Results: The serum FT 4 levels in group A (16.98±2.92 pmol / L), group B (1.84±0.44 pmol / L) and group C (1.35 ±0.37 pmol /L) eight weeks after 131 I injection were decreased, and had significant difference compared with group D (P 4 levels in group B and C were significantly lower than that in group A (P 0.05). Orbital tissue in experimental group showed mucoid degeneration and edema, the extent was about 25% in group A, 50% in group B, 70% in group C. The rats in group B and group C appeared obvious proliferation of fibrous and adipose tissue, muscle fibers degeneration fracture, even extraocular muscles in group C have vacuole formation. Immunohistochemical analysis displayed highest SSTR5 distribution and strongest expression was in extraocular muscle of group C, second in A B combination group (A and B groups)and weakest in group D. There were significant differences between A B combination group,group C and group D (P 0.05). Conclusion: This study observed the distribution and expression of SSTR2 and SSTR5 in extraocular muscle on the established hypothyroidism animal model. It is some significance for understanding the mechanism of somatostatin receptors in occurrence and development of TAO, similar to provide a reference for the use of somatostatin analogue orbital imaging

  9. Disinhibition in learning and memory circuits: New vistas for somatostatin interneurons and long-term synaptic plasticity.

    Science.gov (United States)

    Artinian, Julien; Lacaille, Jean-Claude

    2017-11-23

    Neural circuit functions involve finely controlled excitation/inhibition interactions that allow complex neuronal computations and support high order brain functions such as learning and memory. Disinhibition, defined as a transient brake on inhibition that favors excitation, recently appeared to be a conserved circuit mechanism implicated in various functions such as sensory processing, learning and memory. Although vasoactive intestinal polypeptide (VIP) interneurons are considered to be the main disinhibitory cells, recent studies highlighted a pivotal role of somatostatin (SOM) interneurons in inhibiting GABAergic interneurons and promoting principal cell activation. Interestingly, long-term potentiation of excitatory input synapses onto hippocampal SOM interneurons is proposed as a lasting mechanism for regulation of disinhibition of principal neurons. Such regulation of network metaplasticity may be important for hippocampal-dependent learning and memory. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Selective termination, fetal reduction and analogical reasoning.

    Science.gov (United States)

    Pennings, G

    2013-06-01

    Analogical reasoning is a basic method in bioethics. Its main purpose is to transfer the rule from an existing or known situation to a new and problematic situation. This commentary applies the lifeboat analogy to the context of selective termination and fetal reduction. It turns out that the analogy is only partially helpful as the main principle in the case of selective termination is the procreative beneficence principle. However, the wide person-affecting form of this principle doubly justifies selective termination: i.e. one prevents the harm caused by the birth of an affected child and one increases the life chances of the remaining fetuses. I conclude, however, that all analogies are basically flawed since they assume that fetuses as such have interests. I argue that fetuses only have interests to the extent that they are potential future persons. Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  11. An Electrical Analog Computer for Poets

    Science.gov (United States)

    Bruels, Mark C.

    1972-01-01

    Nonphysics majors are presented with a direct current experiment beyond Ohms law and series and parallel laws. This involves construction of an analog computer from common rheostats and student-assembled voltmeters. (Author/TS)

  12. Pentagastrin analogs containing α-aminooxy acids

    International Nuclear Information System (INIS)

    Balaspiri, L.; Kovacs, L.; Kovacs, K.; Varga, L.; Varro, V.; Schoen, I.; Kisfaludy, L.

    1982-01-01

    Two 14 C-labelled pentagastrin analogs of different specific radioactivities, containing α-aminooxy acids, have been synthesised to study their biological effects in the gastro-intestinal tract. (U.K.)

  13. Quantum States Transfer by Analogous Bell States

    International Nuclear Information System (INIS)

    Mei Di; Li Chong; Yang Guohui; Song Heshan

    2008-01-01

    Transmitting quantum states by channels of analogous Bell states is studied in this paper. We analyze the transmitting process, constructed the probabilitic unitary operator, and gain the largest successful transfer quantum state probability.

  14. Current knowledge on the sensitivity of the 68Ga-somatostatin receptor positron emission tomography and the SUVmax reference range for management of pancreatic neuroendocrine tumours

    International Nuclear Information System (INIS)

    Virgolini, Irene; Gabriel, Michael; Kroiss, Alexander; Guggenberg, Elisabeth von; Prommegger, Rupert; Warwitz, Boris; Nilica, Bernhard; Roig, Ilanos Geraldo; Rodrigues, Margarida; Uprimny, Christian

    2016-01-01

    Physiologically increased pancreatic uptake at the head/uncinate process is observed in more than one-third of patients after injection of one of the three 68 Ga-labelled octreotide-based peptides used for somatostatin (sst) receptor (r) imaging. There are minor differences between these 68 Ga-sstr-binding peptides in the imaging setting. On 68 Ga-sstr-imaging the physiological uptake can be diffuse or focal and usually remains stable over time. Differences in the maximal standardised uptake values (SUV max ) reported for the normal pancreas as well as for pancreatic neuroendocrine tumour (PNET) lesions may be related to several factors, including (a) differences in the peptide binding affinities as well as differences in sstr subtype expression of pancreatic α- and β-cells, and heterogeneity / density of tumour cells, (b) differences in scanner resolution, image reconstruction techniques and acquisition protocols, (c) mostly retrospective study designs, (d) mixed patient populations, or (e) interference with medications such as treatment with long-acting sst analogues. The major limitation in most of the studies lies in the lack of histopathological confirmation of abnormal findings. There is a significant overlap between the calculated SUV max -values for physiological pancreas and PNET-lesions of the head/uncinate process that do not favour the use of quantitative parameters in the clinical setting. Anecdotal long-term follow-up studies have even indicated that increased uptake in the head/uncinate process still can turn out to be malignant over years of follow up. SUV max -data for the pancreatic body and tail are limited. Therefore, any visible focal tracer uptake in the pancreas must be considered as suspicious for malignancy irrespective of quantitative parameters. In general, sstr-PET/CT has significant implications for the management of NET patients leading to a change in treatment decision in about one-third of patients. Therefore, follow-up with 68 Ga

  15. Current knowledge on the sensitivity of the (68)Ga-somatostatin receptor positron emission tomography and the SUVmax reference range for management of pancreatic neuroendocrine tumours.

    Science.gov (United States)

    Virgolini, Irene; Gabriel, Michael; Kroiss, Alexander; von Guggenberg, Elisabeth; Prommegger, Rupert; Warwitz, Boris; Nilica, Bernhard; Roig, Llanos Geraldo; Rodrigues, Margarida; Uprimny, Christian

    2016-10-01

    Physiologically increased pancreatic uptake at the head/uncinate process is observed in more than one-third of patients after injection of one of the three (68)Ga-labelled octreotide-based peptides used for somatostatin (sst) receptor (r) imaging. There are minor differences between these (68)Ga-sstr-binding peptides in the imaging setting. On (68)Ga-sstr-imaging the physiological uptake can be diffuse or focal and usually remains stable over time. Differences in the maximal standardised uptake values (SUVmax) reported for the normal pancreas as well as for pancreatic neuroendocrine tumour (PNET) lesions may be related to several factors, including (a) differences in the peptide binding affinities as well as differences in sstr subtype expression of pancreatic α- and β-cells, and heterogeneity / density of tumour cells, (b) differences in scanner resolution, image reconstruction techniques and acquisition protocols, (c) mostly retrospective study designs, (d) mixed patient populations, or (e) interference with medications such as treatment with long-acting sst analogues. The major limitation in most of the studies lies in the lack of histopathological confirmation of abnormal findings. There is a significant overlap between the calculated SUVmax-values for physiological pancreas and PNET-lesions of the head/uncinate process that do not favour the use of quantitative parameters in the clinical setting. Anecdotal long-term follow-up studies have even indicated that increased uptake in the head/uncinate process still can turn out to be malignant over years of follow up. SUVmax-data for the pancreatic body and tail are limited. Therefore, any visible focal tracer uptake in the pancreas must be considered as suspicious for malignancy irrespective of quantitative parameters. In general, sstr-PET/CT has significant implications for the management of NET patients leading to a change in treatment decision in about one-third of patients. Therefore, follow-up with (68)Ga

  16. High-frequency analog integrated circuit design

    CERN Document Server

    1995-01-01

    To learn more about designing analog integrated circuits (ICs) at microwave frequencies using GaAs materials, turn to this text and reference. It addresses GaAs MESFET-based IC processing. Describes the newfound ability to apply silicon analog design techniques to reliable GaAs materials and devices which, until now, was only available through technical papers scattered throughout hundred of articles in dozens of professional journals.

  17. Emergent Explorations: Analog and Digital Scripting

    OpenAIRE

    Worden, Alexander

    2011-01-01

    This book documents an exploration of emergent and linear modes of defining space, form, and structure. The thesis highlights a dialog between analog and digital modeling techniques, in concept and project development. It identifies that analog modeling techniques, coupled with judgment, can be used to develop complex forms. The thesis project employs critical judgment and the textile techniques of crochet as a vehicle generate form. Crochet lends itself to this investigation because it ...

  18. An analog integrated circuit design laboratory

    OpenAIRE

    Mondragon-Torres, A.F.; Mayhugh, Jr.; Pineda de Gyvez, J.; Silva-Martinez, J.; Sanchez-Sinencio, E.

    2003-01-01

    We present the structure of an analog integrated circuit design laboratory to instruct at both, senior undergraduate and entry graduate levels. The teaching material includes: a laboratory manual with analog circuit design theory, pre-laboratory exercises and circuit design specifications; a reference web page with step by step instructions and examples; the use of mathematical tools for automation and analysis; and state of the art CAD design tools in use by industry. Upon completion of the ...

  19. HAPS, a Handy Analog Programming System

    DEFF Research Database (Denmark)

    Højberg, Kristian Søe

    1975-01-01

    HAPS (Hybrid Analog Programming System) is an analog compiler that can be run on a minicomputer in an interactive mode. Essentially HAPS is written in FORTRAN. The equations to be programmed for an ana log computer are read in by using a FORTRAN-like notation. The input must contain maximum...... and emphasizes the limitations HAPS puts on equation structure, types of computing circuit, scaling, and static testing....

  20. Evaluation of somatostatin receptors in large cell pulmonary neuroendocrine carcinoma with 99mTc-EDDA/HYNIC-TOC scintigraphy.

    Science.gov (United States)

    Nocuń, Anna; Chrapko, Beata; Gołębiewska, Renata; Stefaniak, Bogusław; Czekajska-Chehab, Elżbieta

    2011-06-01

    Large cell pulmonary neuroendocrine carcinoma (LCNEC) is a poorly differentiated and high-grade neoplasm. It is positioned between an atypical carcinoid and small cell neuroendocrine carcinoma of the lung in a distinct family of pulmonary neuroendocrine tumors. The aim of our study was to detect somatostatin receptors in this uncommon malignancy and to evaluate the sensitivity of somatostatin receptor scintigraphy (SRS) in LCNEC staging. We analyzed data of 26 patients (mean age: 61.5±7.9 years) with histologically confirmed diagnosis of LCNEC, including 18 cases not treated surgically and eight patients after the resection of the primary tumor. SRS was carried out with technetium-99m ethylene diamine-diacetic acid/hydrazinonicotinyl-Tyr3-octreotide (Tc-TOC). A visual analysis of scintigraphic images was done with reference to conventional imaging modalities (computed tomography and bone sicintigraphy). SRS sensitivity for the detection of primary lesions, supradiaphragmatic metastases, and infradiaphragmatic metastases was 100, 83.3%, and 0%, respectively. Five out of 13 metastases to the liver appeared on SRS as photopenic foci, visible on the background of physiological hepatic activity. Only one of the nine metastases to the skeletal system was found by SRS with sensitivity as low as 11.1%. The overall SRS sensitivity for the detection of secondary lesions and of all lesions was 54.8 and 62.2%, respectively. Within a rather large series of LCNEC, the primary tumor showed an uptake of Tc-TOC in all cases, whereas some metastases did show Tc-TOC uptake and some others did not.

  1. Role of high mobility group box-1 and protection of growth hormone and somatostatin in severe acute pancreatitis

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Y.F. [Department of Surgery, Huashan Hospital, Fudan University, Shanghai (China); Wu, M. [Department of Surgery, Jinshan Pavilion Forest Hospital, Shanghai (China); Ma, B.J.; Cai, D.A.; Yin, B.B. [Department of Surgery, Huashan Hospital, Fudan University, Shanghai (China)

    2014-09-12

    In this study, we investigated the potential role of high-mobility group box 1 (HMGB1) in severe acute pancreatitis (SAP) and the effects of growth hormone (G) and somatostatin (S) in SAP rats. The rats were randomly divided into 6 groups of 20 each: sham-operated, SAP, SAP+saline, SAP+G, SAP+S and SAP+G+S. Ileum and pancreas tissues of rats in each group were evaluated histologically. HMGB1 mRNA expression was measured by reverse transcription-PCR. Levels of circulating TNF-α, IL-1, IL-6, and endotoxin were also measured. In the SAP group, interstitial congestion and edema, inflammatory cell infiltration, and interstitial hemorrhage occurred in ileum and pancreas tissues. The levels of HMGB1, TNF-α, IL-1, IL-6 and endotoxin were significantly up-regulated in the SAP group compared with those in the sham-operated group, and the 7-day survival rate was 0%. In the SAP+G and SAP+S groups, the inflammatory response of the morphological structures was alleviated, the levels of HMGB1, TNF-α, IL-1, IL-6, and endotoxin were significantly decreased compared with those in the SAP group, and the survival rate was increased. Moreover, in the SAP+G+S group, all histological scores were significantly improved and the survival rate was significantly higher compared with the SAP group. In conclusion, HMGB1 might participate in pancreas and ileum injury in SAP. Growth hormone and somatostatin might play a therapeutic role in the inflammatory response of SAP.

  2. Role of high mobility group box-1 and protection of growth hormone and somatostatin in severe acute pancreatitis

    International Nuclear Information System (INIS)

    Wang, Y.F.; Wu, M.; Ma, B.J.; Cai, D.A.; Yin, B.B.

    2014-01-01

    In this study, we investigated the potential role of high-mobility group box 1 (HMGB1) in severe acute pancreatitis (SAP) and the effects of growth hormone (G) and somatostatin (S) in SAP rats. The rats were randomly divided into 6 groups of 20 each: sham-operated, SAP, SAP+saline, SAP+G, SAP+S and SAP+G+S. Ileum and pancreas tissues of rats in each group were evaluated histologically. HMGB1 mRNA expression was measured by reverse transcription-PCR. Levels of circulating TNF-α, IL-1, IL-6, and endotoxin were also measured. In the SAP group, interstitial congestion and edema, inflammatory cell infiltration, and interstitial hemorrhage occurred in ileum and pancreas tissues. The levels of HMGB1, TNF-α, IL-1, IL-6 and endotoxin were significantly up-regulated in the SAP group compared with those in the sham-operated group, and the 7-day survival rate was 0%. In the SAP+G and SAP+S groups, the inflammatory response of the morphological structures was alleviated, the levels of HMGB1, TNF-α, IL-1, IL-6, and endotoxin were significantly decreased compared with those in the SAP group, and the survival rate was increased. Moreover, in the SAP+G+S group, all histological scores were significantly improved and the survival rate was significantly higher compared with the SAP group. In conclusion, HMGB1 might participate in pancreas and ileum injury in SAP. Growth hormone and somatostatin might play a therapeutic role in the inflammatory response of SAP

  3. An evaluation of the effects of somatostatin analogue therapy in non-functioning pituitary adenomas in comparison to acromegaly.

    Science.gov (United States)

    Zawada, Natalia Bożena; Kunert-Radek, Jolanta; Pawlikowski, Marek; Pisarek, Hanna; Radek, Maciej

    2016-01-01

    Non-functioning pituitary adenomas (NFPA) are often diagnosed late as invasive macroadenomas. The surgical resection is usually incomplete and about 50% of patients require additional surgery. Recent data suggest that somatostatin analogues (SSA), so important in the pharmacotherapy of acromegaly, can also be effective in the management of NFPA. We analysed data of patients who had been treated up to 10 years previously with SSA: 40 with acromegaly (23 - primary, 17 - recurrent tumours) and 22 with NFPA (4 - primary, 18 - recurrent tumours). Hormonal profile, dynamics of tumour size change, ophthalmic syndromes, somatostatin receptor (SSTR) scintigraphy, and immunohistochemistry of SSTR subtypes of operated tumours as well as side effects were investigated. Biochemical cure of acromegaly was achieved in 57.5% of patients, while reduction of tumour size was observed in 37% of patients and it was more frequent in not-operated cases. Regarding NFPA, stabilisation of tumour size was noticed in 68% of patients. Tumour shrinkage was reported in 9% of cases, but in 23% of the study group the adenoma size increased with indication for reoperation. The efficacy of SSA in NFPA is much lower in comparison to their well-established effects in the treatment of acromegaly. Stabilisation of tumour size, which is observed in the majority of NFPA, is significantly more frequent in comparison to the natural history of untreated NFPA and our previous studies as well. Analysis of SSTR subtypes is an argument in favour of introduction of novel broad-spectrum SSA that may be more effective in the treatment of NFPA. Referring to acromegaly, adenoma size decrease was reported more frequently in primary therapy. Considering recurrent tumours better outcomes were achieved in patients who were pre-treated with SSA before planned surgery. (Endokrynol Pol 2016; 67 (3): 292-298).

  4. Development of 99mTc labelled somatostatin analogues and evaluation of their radiochemical and biological behaviour

    International Nuclear Information System (INIS)

    Gano, L.; Patricio, L.

    2001-01-01

    Conjugates of two somatostatin analogues, octreotide and RC-160, with HYNIC were synthesized, characterized and purified by reverse phase HPLC. Radiolabelling of the conjugates with 99m Tc was achieved using tricine as co-ligand. High labelling efficiencies were obtained and 99m Tc peptides with high radiochemical purity were found when analysed both by ITLC and HPLC. In vitro stability of 99m Tc-peptides in human serum and towards cysteine challenge was determined by Cellogel electrophoresis and HPLC after ultrafiltration of serum solution through a 20 kDa cut off membrane. Biodistribution studies were performed in healthy mice at 5 and 30 minutes and 1, 2, 4 and 24 h post-injection. Urine and blood samples were collected at sacrifice time. Samples of urine and ultrafiltrate murine serum were analysed by electrophoresis and reverse phase HPLC in order to get some information about radiocompounds metabolism. Biological distribution of 99m Tc octreotide was also assayed in mice pre-treated with an excess of unlabelled peptide. From our results we conclude that this labelling method led to stable 99m Tc complexes both in vitro and in vivo when high specific activities (37-72 GBq/μmole) were used. Biodistribution studies of both 99m Tc-peptides indicated a radioactivity distribution profile with significant differences especially in the liver uptake that is higher for 99m Tc RC-160. However, a rapid blood clearance was obtained for both radiolabelled peptides, and the urine analysis indicated that 99m Tc peptide is mostly excreted as the initial complex. Pre-treatment with unlabelled peptide did not affect renal excretion of 99m TOC but pancreas and intestine radioactive uptake was significantly lower, indicating saturation of somatostatin receptors and selective uptake. (author)

  5. Children's analogical reasoning about natural phenomena.

    Science.gov (United States)

    Pauen, S; Wilkening, F

    1997-10-01

    This report investigates children's analogical reasoning in a physics task, using an analogy generated by the children rather than by the experimenter. A total of 127 elementary school children took part in three related studies. Children learned to predict the behavior of a balance scale. Later, they were asked to solve a force interaction problem. Two versions of the balance scale training were devised: version A suggested an incorrect solution to the target problem (negative analogy), and version B suggested a correct solution to the target problem (positive analogy). In Study 1, 9- to 10-year-olds showed spontaneous transfer in both training conditions. In Study 2, 7-year-olds did not show any transfer in the positive analogy condition. Study 3 revealed that the lack of transfer in younger children was not due to a failure either to notice the analogy or to perform the mapping. Instead, 7-year-olds transferred only selected aspects of the correct solution. Copyright 1997 Academic Press.

  6. Working memory predicts children's analogical reasoning.

    Science.gov (United States)

    Simms, Nina K; Frausel, Rebecca R; Richland, Lindsey E

    2018-02-01

    Analogical reasoning is the cognitive skill of drawing relationships between representations, often between prior knowledge and new representations, that allows for bootstrapping cognitive and language development. Analogical reasoning proficiency develops substantially during childhood, although the mechanisms underlying this development have been debated, with developing cognitive resources as one proposed mechanism. We explored the role of executive function (EF) in supporting children's analogical reasoning development, with the goal of determining whether predicted aspects of EF were related to analogical development at the level of individual differences. We assessed 5- to 11-year-old children's working memory, inhibitory control, and cognitive flexibility using measures from the National Institutes of Health Toolbox Cognition battery. Individual differences in children's working memory best predicted performance on an analogical mapping task, even when controlling for age, suggesting a fundamental interrelationship between analogical reasoning and working memory development. These findings underscore the need to consider cognitive capacities in comprehensive theories of children's reasoning development. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Anti-Plasmodium activity of ceramide analogs

    Directory of Open Access Journals (Sweden)

    Gatt Shimon

    2004-12-01

    Full Text Available Abstract Background Sphingolipids are key molecules regulating many essential functions in eukaryotic cells and ceramide plays a central role in sphingolipid metabolism. A sphingolipid metabolism occurs in the intraerythrocytic stages of Plasmodium falciparum and is associated with essential biological processes. It constitutes an attractive and potential target for the development of new antimalarial drugs. Methods The anti-Plasmodium activity of a series of ceramide analogs containing different linkages (amide, methylene or thiourea linkages between the fatty acid part of ceramide and the sphingoid core was investigated in culture and compared to the sphingolipid analog PPMP (d,1-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol. This analog is known to inhibit the parasite sphingomyelin synthase activity and block parasite development by preventing the formation of the tubovesicular network that extends from the parasitophorous vacuole to the red cell membrane and delivers essential extracellular nutrients to the parasite. Results Analogs containing methylene linkage showed a considerably higher anti-Plasmodium activity (IC50 in the low nanomolar range than PPMP and their counterparts with a natural amide linkage (IC50 in the micromolar range. The methylene analogs blocked irreversibly P. falciparum development leading to parasite eradication in contrast to PPMP whose effect is cytostatic. A high sensitivity of action towards the parasite was observed when compared to their effect on the human MRC-5 cell growth. The toxicity towards parasites did not correlate with the inhibition by methylene analogs of the parasite sphingomyelin synthase activity and the tubovesicular network formation, indicating that this enzyme is not their primary target. Conclusions It has been shown that ceramide analogs were potent inhibitors of P. falciparum growth in culture. Interestingly, the nature of the linkage between the fatty acid part and the

  8. NaturAnalogs for the Unsaturated Zone

    Energy Technology Data Exchange (ETDEWEB)

    A. Simmons; A. Unger; M. Murrell

    2000-03-08

    The purpose of this Analysis/Model Report (AMR) is to document natural and anthropogenic (human-induced) analog sites and processes that are applicable to flow and transport processes expected to occur at the potential Yucca Mountain repository in order to build increased confidence in modeling processes of Unsaturated Zone (UZ) flow and transport. This AMR was prepared in accordance with ''AMR Development Plan for U0135, Natural Analogs for the UZ'' (CRWMS 1999a). Knowledge from analog sites and processes is used as corroborating information to test and build confidence in flow and transport models of Yucca Mountain, Nevada. This AMR supports the Unsaturated Zone (UZ) Flow and Transport Process Model Report (PMR) and the Yucca Mountain Site Description. The objectives of this AMR are to test and build confidence in the representation of UZ processes in numerical models utilized in the UZ Flow and Transport Model. This is accomplished by: (1) applying data from Boxy Canyon, Idaho in simulations of UZ flow using the same methodologies incorporated in the Yucca Mountain UZ Flow and Transport Model to assess the fracture-matrix interaction conceptual model; (2) Providing a preliminary basis for analysis of radionuclide transport at Pena Blanca, Mexico as an analog of radionuclide transport at Yucca Mountain; and (3) Synthesizing existing information from natural analog studies to provide corroborating evidence for representation of ambient and thermally coupled UZ flow and transport processes in the UZ Model.

  9. Analog forecasting with dynamics-adapted kernels

    Science.gov (United States)

    Zhao, Zhizhen; Giannakis, Dimitrios

    2016-09-01

    Analog forecasting is a nonparametric technique introduced by Lorenz in 1969 which predicts the evolution of states of a dynamical system (or observables defined on the states) by following the evolution of the sample in a historical record of observations which most closely resembles the current initial data. Here, we introduce a suite of forecasting methods which improve traditional analog forecasting by combining ideas from kernel methods developed in harmonic analysis and machine learning and state-space reconstruction for dynamical systems. A key ingredient of our approach is to replace single-analog forecasting with weighted ensembles of analogs constructed using local similarity kernels. The kernels used here employ a number of dynamics-dependent features designed to improve forecast skill, including Takens’ delay-coordinate maps (to recover information in the initial data lost through partial observations) and a directional dependence on the dynamical vector field generating the data. Mathematically, our approach is closely related to kernel methods for out-of-sample extension of functions, and we discuss alternative strategies based on the Nyström method and the multiscale Laplacian pyramids technique. We illustrate these techniques in applications to forecasting in a low-order deterministic model for atmospheric dynamics with chaotic metastability, and interannual-scale forecasting in the North Pacific sector of a comprehensive climate model. We find that forecasts based on kernel-weighted ensembles have significantly higher skill than the conventional approach following a single analog.

  10. Analogy, higher order thinking, and education.

    Science.gov (United States)

    Richland, Lindsey Engle; Simms, Nina

    2015-01-01

    Analogical reasoning, the ability to understand phenomena as systems of structured relationships that can be aligned, compared, and mapped together, plays a fundamental role in the technology rich, increasingly globalized educational climate of the 21st century. Flexible, conceptual thinking is prioritized in this view of education, and schools are emphasizing 'higher order thinking', rather than memorization of a cannon of key topics. The lack of a cognitively grounded definition for higher order thinking, however, has led to a field of research and practice with little coherence across domains or connection to the large body of cognitive science research on thinking. We review literature on analogy and disciplinary higher order thinking to propose that relational reasoning can be productively considered the cognitive underpinning of higher order thinking. We highlight the utility of this framework for developing insights into practice through a review of mathematics, science, and history educational contexts. In these disciplines, analogy is essential to developing expert-like disciplinary knowledge in which concepts are understood to be systems of relationships that can be connected and flexibly manipulated. At the same time, analogies in education require explicit support to ensure that learners notice the relevance of relational thinking, have adequate processing resources available to mentally hold and manipulate relations, and are able to recognize both the similarities and differences when drawing analogies between systems of relationships. © 2015 John Wiley & Sons, Ltd.

  11. An analog silicon retina with multichip configuration.

    Science.gov (United States)

    Kameda, Seiji; Yagi, Tetsuya

    2006-01-01

    The neuromorphic silicon retina is a novel analog very large scale integrated circuit that emulates the structure and the function of the retinal neuronal circuit. We fabricated a neuromorphic silicon retina, in which sample/hold circuits were embedded to generate fluctuation-suppressed outputs in the previous study [1]. The applications of this silicon retina, however, are limited because of a low spatial resolution and computational variability. In this paper, we have fabricated a multichip silicon retina in which the functional network circuits are divided into two chips: the photoreceptor network chip (P chip) and the horizontal cell network chip (H chip). The output images of the P chip are transferred to the H chip with analog voltages through the line-parallel transfer bus. The sample/hold circuits embedded in the P and H chips compensate for the pattern noise generated on the circuits, including the analog communication pathway. Using the multichip silicon retina together with an off-chip differential amplifier, spatial filtering of the image with an odd- and an even-symmetric orientation selective receptive fields was carried out in real time. The analog data transfer method in the present multichip silicon retina is useful to design analog neuromorphic multichip systems that mimic the hierarchical structure of neuronal networks in the visual system.

  12. A fast multichannel analog storage system

    International Nuclear Information System (INIS)

    Freytag, D.R.

    1983-01-01

    A Multichannel Analog Storage System based on a commercial 32-channel parallel in/serial out (PISO) analog shift register is described. The basic unit is a single width CAMAC module containing 512 analog cells and the associated logic for data storage and subsequent readout. At sampling rates of up to 30 MHz the signals are strobed directly into the PISO. At higher rates signals are strobed into a fast presampling stage and subsequently transferred in block form into an array of PISO's. Sampling rates of 300 MHz have been achieved with the present device and 1000 MHz are possible with improved signal drivers. The system is well suited for simultaneous handling of many signal channels with moderate numbers of samples in each channel. RMS noise over full scale signal has been measured as 1:3000 (approx. =11 bit). However, nonlinearities in the response and differences in sensitivity of the analog cells require an elaborate calibration system in order to realize 11 bit accuracy for the analog information

  13. Neurotoxic Alkaloids: Saxitoxin and Its Analogs

    Directory of Open Access Journals (Sweden)

    Troco K. Mihali

    2010-07-01

    Full Text Available Saxitoxin (STX and its 57 analogs are a broad group of natural neurotoxic alkaloids, commonly known as the paralytic shellfish toxins (PSTs. PSTs are the causative agents of paralytic shellfish poisoning (PSP and are mostly associated with marine dinoflagellates (eukaryotes and freshwater cyanobacteria (prokaryotes, which form extensive blooms around the world. PST producing dinoflagellates belong to the genera Alexandrium, Gymnodinium and Pyrodinium whilst production has been identified in several cyanobacterial genera including Anabaena, Cylindrospermopsis, Aphanizomenon Planktothrix and Lyngbya. STX and its analogs can be structurally classified into several classes such as non-sulfated, mono-sulfated, di-sulfated, decarbamoylated and the recently discovered hydrophobic analogs—each with varying levels of toxicity. Biotransformation of the PSTs into other PST analogs has been identified within marine invertebrates, humans and bacteria. An improved understanding of PST transformation into less toxic analogs and degradation, both chemically or enzymatically, will be important for the development of methods for the detoxification of contaminated water supplies and of shellfish destined for consumption. Some PSTs also have demonstrated pharmaceutical potential as a long-term anesthetic in the treatment of anal fissures and for chronic tension-type headache. The recent elucidation of the saxitoxin biosynthetic gene cluster in cyanobacteria and the identification of new PST analogs will present opportunities to further explore the pharmaceutical potential of these intriguing alkaloids.

  14. Natural Analogs for the Unsaturated Zone

    International Nuclear Information System (INIS)

    Simmons, A.; Unger, A.; Murrell, M.

    2000-01-01

    The purpose of this Analysis/Model Report (AMR) is to document natural and anthropogenic (human-induced) analog sites and processes that are applicable to flow and transport processes expected to occur at the potential Yucca Mountain repository in order to build increased confidence in modeling processes of Unsaturated Zone (UZ) flow and transport. This AMR was prepared in accordance with ''AMR Development Plan for U0135, Natural Analogs for the UZ'' (CRWMS 1999a). Knowledge from analog sites and processes is used as corroborating information to test and build confidence in flow and transport models of Yucca Mountain, Nevada. This AMR supports the Unsaturated Zone (UZ) Flow and Transport Process Model Report (PMR) and the Yucca Mountain Site Description. The objectives of this AMR are to test and build confidence in the representation of UZ processes in numerical models utilized in the UZ Flow and Transport Model. This is accomplished by: (1) applying data from Boxy Canyon, Idaho in simulations of UZ flow using the same methodologies incorporated in the Yucca Mountain UZ Flow and Transport Model to assess the fracture-matrix interaction conceptual model; (2) Providing a preliminary basis for analysis of radionuclide transport at Pena Blanca, Mexico as an analog of radionuclide transport at Yucca Mountain; and (3) Synthesizing existing information from natural analog studies to provide corroborating evidence for representation of ambient and thermally coupled UZ flow and transport processes in the UZ Model

  15. Somatostatin Receptor SPECT/CT using 99mTc Labeled HYNIC-TOC Aids in Diagnosis of Primary Optic Nerve Sheath Meningioma.

    Science.gov (United States)

    Chandra, Piyush; Purandare, Nilendu; Shah, Sneha; Agrawal, Archi; Rangarajan, Venkatesh

    2017-01-01

    Primary optic nerve sheath meningiomas (ONSM) are rare, benign and slow growing tumor involving the intra-orbital/intra-canalicular segment of the optic nerve. Untreated, they can potentially lead to visual deterioration. Magnetic resonance (MR) is the gold standard imaging modality for diagnosing the entity. Often, a clinical dilemma exists to narrow the differential diagnosis of an enhancing intra-orbital mass on MR. Molecular imaging provides a high degree of precision in diagnosing meningioma in view of relatively high levels of somatostatin receptor expression by these tumors. The following case demonstrates the potential clinical utility of somatostatin receptor SPECT using 99m Tc- labeled HYNIC-TOC in clinical diagnosis of ONSM.

  16. Students' Pre- and Post-Teaching Analogical Reasoning when They Draw Their Analogies

    Science.gov (United States)

    Mozzer, Nilmara Braga; Justi, Rosaria

    2012-01-01

    Analogies are parts of human thought. From them, we can acquire new knowledge or change that which already exists in our cognitive structure. In this sense, understanding the analogical reasoning process becomes an essential condition to understand how we learn. Despite the importance of such an understanding, there is no general agreement in…

  17. Preparation and biological evaluation of [(99m)Tc/EDDA/Tricine/HYNIC(0), BzThi(3)]-octreotide for somatostatin receptor-positive tumor imaging.

    Science.gov (United States)

    Erfani, Mostafa; Shafiei, Mohammad; Mazidi, Mohammad; Goudarzi, Mostafa

    2013-04-01

    Somatostatin-derived analogues play an important role in the diagnosis and treatment of neuroendocrine tumors. The aim of this study was to evaluate a new somatostatin analogue designed for labeling with (99m)Tc: [6-hydrazinopyridine-3-carboxylic acid (HYNIC(0)), β-(3-benzothienyl)-Ala (BzThi(3))]-octreotide ([HYNIC]-BOC), using ethylenediamine-N,N'-diacetic acid (EDDA) and tricine as coligands. Synthesis was performed on a solid phase using a standard Fmoc strategy. The HYNIC-peptide conjugate was radiolabeled with (99m)Tc and characterized by ITLC and high-performance liquid chromatography (HPLC). In vitro studies were carried out in sstr2 expressing AR4-2J cell lines. In vivo distribution studies were performed in rats bearing the AR4-2J tumor. The radiolabeled complex could be prepared at high-specific activities and >95% radiochemical yield as determined by HPLC. The peptide conjugate showed high-affinity binding for sstr2. The radioligand showed high and specific internalization into AR4-2J cells (18.19%±0.21% at 4 hours). In vivo distribution studies in rats bearing tumor have shown a receptor-specific uptake of radioactivity in somatostatin receptor-positive organs. After 4 hours, uptake in the AR4-2J tumor was 1.71%±0.36% injected dose per gram tissue (%ID/g). These data show that [(99m)Tc/EDDA/Tricine/HYNIC(0), BzThi(3)]-octreotide is a specific radioligand for the somatostatin receptor-positive tumors and is a suitable candidate for clinical studies.

  18. Molecular imaging with {sup 68}Ga-SSTR PET/CT and correlation to immunohistochemistry of somatostatin receptors in neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Kaemmerer, Daniel; Haugvik, Sven-Petter; Hommann, Merten [Zentralklinik Bad Berka GmbH, Department of General and Visceral Surgery, Bad Berka (Germany); Peter, Luisa; Lupp, Amelie; Schulz, Stefan [University of Jena, Department of Pharmacology and Toxicology, Jena (Germany); Saenger, Joerg [Laboratory of Pathology and Cytology, Bad Berka (Germany); Prasad, Vikas; Kulkarni, Harshad; Baum, Richard Paul [Zentralklinik Bad Berka, Department of Nuclear Medicine and Center for PET, Bad Berka (Germany)

    2011-09-15

    Somatostatin receptors (SSTR) are known for an overexpression in gastroenteropancreatic neuroendocrine tumours (GEP-NET). The aim of the present study was to find out if the receptor density predicted by the semi-quantitative parameters generated from the static positron emission tomography (PET/CT) correlated with the in vitro immunohistochemistry using a novel rabbit monoclonal anti-SSTR2A antibody (clone UMB-1) for specific SSTR2A immunohistochemistry and polyclonal antibodies for SSTR1 and 3-5. Overall 14 surgical specimens generated from 34 histologically documented GEP-NET patients were correlated with the preoperative {sup 68}Ga-DOTA-NOC PET/CT. Quantitative assessment of the receptor density was done using the immunoreactive score (IRS) of Remmele and Stegner; the additional 4-point IRS classification for immunohistochemistry and standardized uptake values (SUV{sub max} and SUV{sub mean}) were used for PET/CT. The IRS for SSTR2A and SSTR5 correlated highly significant with the SUV{sub max} on the PET/CT (p < 0.001; p < 0.05) and the IRS for SSTR2A with the SUV{sub mean} (p < 0.013). The level of SSTR2A score correlated significantly with chromogranin A staining and indirectly to the tumour grading. The highly significant correlation between SSTR2A and SSTR5 and the SUV{sub max} on the {sup 68}Ga-DOTA-NOC PET/CT scans is concordant with the affinity profile of {sup 68}Ga-DOTA-NOC to the SSTR subtypes and demonstrates the excellent qualification of somatostatin analogues in the diagnostics of NET. This study correlating somatostatin receptor imaging using {sup 68}Ga-DOTA-NOC PET/CT with immunohistochemically analysed SSTR also underlines the approval of therapy using somatostatin analogues, follow-up imaging as well as radionuclide therapy. (orig.)

  19. Comparing the Cost of Treatment with Octreotide Long-Acting Release versus Lanreotide in Patients with Metastatic Gastrointestinal Neuroendocrine Tumors.

    Science.gov (United States)

    Ayyagari, Rajeev; Neary, Maureen; Li, Shang; Rokito, Ariel; Yang, Hongbo; Xie, Jipan; Benson, Al B

    2017-11-01

    The 2 somatostatin analogs currently recommended by the National Comprehensive Cancer Network for the treatment of gastrointestinal (GI) neuroendocrine tumors (NETs) include octreotide long-acting release (Sandostatin LAR) for injectable suspension and lanreotide (Somatuline Depot) injection for subcutaneous use. To estimate the costs to payers associated with 30-mg octreotide LAR and 120-mg lanreotide treatment among patients with metastatic GI-NETs. The costs to payers associated with the 2 drugs were estimated by including the costs of each drug, drug administration, and adverse events. The unit drug costs for octreotide LAR and for lanreotide were obtained from ReadyPrice Wholesale Acquisition Cost; the doses were obtained from published studies. The adverse event rates were obtained from 2 phase 3 clinical trials, PROMID and CLARINET. Deterministic one-way sensitivity analyses were used to assess the impact of modifying assumptions and inputs on the results, including the 2017 Average Sales Price (ASP). All costs were estimated in 2016 US dollars, with a constant discount of 3%. The costs to payers associated with the treatment of GI-NETs during 1-, 3-, and 5-year horizons were $74,566, $180,082, and $262,344, respectively, for octreotide LAR and $84,856, $205,562, and $299,667, respectively, for lanreotide. Thus, octreotide LAR was associated with lower costs by $10,290 (1 year), $25,480 (3 years), and $37,323 (5 years) compared with lanreotide. Over a 5-year horizon, the costs of adverse events and administration accounted for 0.72% of the total cost for octreotide LAR and 0.51% of the total cost for lanreotide. Sensitivity analyses confirmed that the main factor affecting the cost difference was the price of the drugs; analyses using the ASP yielded similar results. For the management of metastatic GI-NETs, the cost to payers of treatment with 30-mg octreotide LAR is considerably lower than with 120-mg lanreotide over 1-, 3-, and 5-year horizons. In the

  20. Changes in analogical reasoning in adulthood.

    Science.gov (United States)

    Clark, E; Gardner, M K; Brown, G; Howell, R J

    1990-01-01

    This study sought to investigate adult intellectual development through an analysis of a particular type of cognitive ability, verbal analogical reasoning. The performance of 60 individuals between the ages of 20 and 79 was compared on 100 verbal analogies. The subjects consisted of six groups of ten individuals each (five males and five females), matched as a group for education and gender. Solution times and error rates served as the dependent measures. Results showed that there was a significant trend for the older subjects (60- and 70-year-olds) to be slower than the young subjects (20-, 30-, 40-, and 50-year-olds), but not necessarily more error prone. These data suggest that verbal analogical reasoning changes with age. Supplemental data demonstrated a change in other abilities as well (i.e., decline in perceptual-motor speed and spatial skill).

  1. Electronic devices for analog signal processing

    CERN Document Server

    Rybin, Yu K

    2012-01-01

    Electronic Devices for Analog Signal Processing is intended for engineers and post graduates and considers electronic devices applied to process analog signals in instrument making, automation, measurements, and other branches of technology. They perform various transformations of electrical signals: scaling, integration, logarithming, etc. The need in their deeper study is caused, on the one hand, by the extension of the forms of the input signal and increasing accuracy and performance of such devices, and on the other hand, new devices constantly emerge and are already widely used in practice, but no information about them are written in books on electronics. The basic approach of presenting the material in Electronic Devices for Analog Signal Processing can be formulated as follows: the study with help from self-education. While divided into seven chapters, each chapter contains theoretical material, examples of practical problems, questions and tests. The most difficult questions are marked by a diamon...

  2. Electrical analog of a Josephson junction

    International Nuclear Information System (INIS)

    Goldman, A.M.

    1979-01-01

    It is noted that a mathematical description of the phase-coupling of two oscillators synchronized by a phase-lock-loop under the influence of thermal white noise is analogous to that of the phase coupling of two superconductors in a Josephson junction also under the influence of noise. This analogy may be useful in studying threshold instabilities of the Josephson junction in regimes not restricted to the case of large damping. This is of interest because the behavior of the mean voltage near the threshold current can be characterized by critical exponents which resemble those exhibited by an order parameter of a continuous phase transition. As it is possible to couple a collection of oscillators together in a chain, the oscillator analogy may also be useful in exploring the dynamics and statistical mechanics of coupled junctions

  3. On Lovelock analogs of the Riemann tensor

    Science.gov (United States)

    Camanho, Xián O.; Dadhich, Naresh

    2016-03-01

    It is possible to define an analog of the Riemann tensor for Nth order Lovelock gravity, its characterizing property being that the trace of its Bianchi derivative yields the corresponding analog of the Einstein tensor. Interestingly there exist two parallel but distinct such analogs and the main purpose of this note is to reconcile both formulations. In addition we will introduce a simple tensor identity and use it to show that any pure Lovelock vacuum in odd d=2N+1 dimensions is Lovelock flat, i.e. any vacuum solution of the theory has vanishing Lovelock-Riemann tensor. Further, in the presence of cosmological constant it is the Lovelock-Weyl tensor that vanishes.

  4. Broadband analog to digital conversion with spatial-spectral holography

    International Nuclear Information System (INIS)

    Babbitt, W. Randall; Neifeld, Mark A.; Merkel, Kristian D.

    2007-01-01

    A new approach to broadband photonic-assisted analog-to-digital converter (ADC) technology is proposed and analyzed. The core of the device is a spatial spectral holographic (SSH) material, which can directly record the signals of interest in the frequency domain. An SSH-ADC acts as a frequency-domain stretch processor, which leverages the high performance of conventional ADCs by converting high bandwidth input signals to low bandwidth output signals without loss of information. Analysis of a 10 GHz bandwidth SSH-ADC predicts that 10-bit performance can be achieved with currently available materials and components. SSH-ADC technology is scalable to bandwidths over 100 GHz with recently developed SSH materials. While the SSH-ADC is a transient digitizer, the spatial parallelism of SSH materials can be utilized to enable continuous digitization

  5. Broadband analog to digital conversion with spatial-spectral holography

    Energy Technology Data Exchange (ETDEWEB)

    Babbitt, W. Randall [Spectrum Lab, Montana State University, Bozeman, MT 59717-3510 (United States)]. E-mail: babbitt@physics.montana.edu; Neifeld, Mark A. [Spectrum Lab, Montana State University, Bozeman, MT 59717-3510 (United States); Merkel, Kristian D. [Spectrum Lab, Montana State University, Bozeman, MT 59717-3510 (United States)

    2007-11-15

    A new approach to broadband photonic-assisted analog-to-digital converter (ADC) technology is proposed and analyzed. The core of the device is a spatial spectral holographic (SSH) material, which can directly record the signals of interest in the frequency domain. An SSH-ADC acts as a frequency-domain stretch processor, which leverages the high performance of conventional ADCs by converting high bandwidth input signals to low bandwidth output signals without loss of information. Analysis of a 10 GHz bandwidth SSH-ADC predicts that 10-bit performance can be achieved with currently available materials and components. SSH-ADC technology is scalable to bandwidths over 100 GHz with recently developed SSH materials. While the SSH-ADC is a transient digitizer, the spatial parallelism of SSH materials can be utilized to enable continuous digitization.

  6. Analogical reasoning for reliability analysis based on generic data

    Energy Technology Data Exchange (ETDEWEB)

    Kozin, Igor O

    1996-10-01

    The paper suggests using the systemic concept 'analogy' for the foundation of an approach to analyze system reliability on the basis of generic data, describing the method of structuring the set that defines analogical models, an approach of transition from the analogical model to a reliability model and a way of obtaining reliability intervals of analogous objects.

  7. Analogical reasoning for reliability analysis based on generic data

    International Nuclear Information System (INIS)

    Kozin, Igor O.

    1996-01-01

    The paper suggests using the systemic concept 'analogy' for the foundation of an approach to analyze system reliability on the basis of generic data, describing the method of structuring the set that defines analogical models, an approach of transition from the analogical model to a reliability model and a way of obtaining reliability intervals of analogous objects

  8. Analogy-Enhanced Instruction: Effects on Reasoning Skills in Science

    Science.gov (United States)

    Remigio, Krisette B.; Yangco, Rosanelia T.; Espinosa, Allen A.

    2014-01-01

    The study examined the reasoning skills of first year high school students after learning general science concepts through analogies. Two intact heterogeneous sections were randomly assigned to Analogy-Enhanced Instruction (AEI) group and Non Analogy-Enhanced (NAEI) group. Various analogies were incorporated in the lessons of the AEI group for…

  9. Perceptions of Rebuttal Analogy: Politeness and Implications for Persuasion.

    Science.gov (United States)

    Whaley, Bryan B.

    1997-01-01

    States that recent theorizing about the role of analogy in persuasion suggests that "rebuttal" analogy addresses two communicative functions by serving as argument and a method of social attack. Examines message receivers' perceptions of rebuttal analogy and rebuttal analogy users. Finds that participants perceived the communicator using…

  10. Enhanced bilateral somatostatin receptor expression in mediastinal lymph nodes (''chimney sign'') in occult metastatic medullary thyroid cancer: a typical site of tumour manifestation?

    International Nuclear Information System (INIS)

    Behr, T.M.; Gratz, S.; Markus, P.M.; Dunn, R.M.; Huefner, M.; Becker, H.; Becker, W.

    1997-01-01

    In medullary thyroid cancer (MTC), post-surgically elevated plasma calcitonin and/or carcinoembryonic antigen levels frequently indicate persisting metastatic disease, although conventional diagnostic procedures fail to localize the responsible lesions (occult disease). Somatostatin analogues have been used successfully in disease localization, but recently concerns have been raised that increased thoracic uptake of indium-111 pentetreotide in patients with previous external beam irradiation may represent a false-positive finding, caused by post-irradiation pulmonary fibrosis. We recently examined seven patients with metastatic MTC by somatostatin receptor scintigraphy (six with occult and one with established disease). In four patients, all of whom had stable or slowly rising tumour marker levels over several years, a chimney-like bilateral mediastinal uptake of indium-111 pentetreotide was found. In two patients with persisting hypercalcitonaemia immediately after primary surgery, supraclavicular lymph node metastases were identified as the responsible lesions. None of these seven patients had prior external beam radiation therapy. In two cases, histological confirmation was obtained. In one patient, disease progression could be shown during follow-up. These data suggest that bilateral mediastinal lymph node involvement is a typical site of disease in slowly progressing occult metastatic MTC; the ''chimney sign'' may represent a typical finding with somatostatin analogues in such cases. Therefore, we believe that even in the case of prior external beam irradiation, mediastinal uptake of octreotide might represent metastatic MTC rather than radiation fibrosis. (orig.). With 2 figs., 1 tab

  11. The emergence of understanding in a computer model of concepts and analogy-making

    Science.gov (United States)

    Mitchell, Melanie; Hofstadter, Douglas R.

    1990-06-01

    This paper describes Copycat, a computer model of the mental mechanisms underlying the fluidity and adaptability of the human conceptual system in the context of analogy-making. Copycat creates analogies between idealized situations in a microworld that has been designed to capture and isolate many of the central issues of analogy-making. In Copycat, an understanding of the essence of a situation and the recognition of deep similarity between two superficially different situations emerge from the interaction of a large number of perceptual agents with an associative, overlapping, and context-sensitive network of concepts. Central features of the model are: a high degree of parallelism; competition and cooperation among a large number of small, locally acting agents that together create a global understanding of the situation at hand; and a computational temperature that measures the amount of perceptual organization as processing proceeds and that in turn controls the degree of randomness with which decisions are made in the system.

  12. An Open-Source Tool Set Enabling Analog-Digital-Software Co-Design

    Directory of Open Access Journals (Sweden)

    Michelle Collins

    2016-02-01

    Full Text Available This paper presents an analog-digital hardware-software co-design environment for simulating and programming reconfigurable systems. The tool simulates, designs, as well as enables experimental measurements after compiling to configurable systems in the same integrated design tool framework. High level software in Scilab/Xcos (open-source programs similar to MATLAB/Simulink that converts the high-level block description by the user to blif format (sci2blif, which acts as an input to the modified VPR tool, including the code v p r 2 s w c s , encoding the specific platform through specific architecture files, resulting in a targetable switch list on the resulting configurable analog–digital system. The resulting tool uses an analog and mixed-signal library of components, enabling users and future researchers access to the basic analog operations/computations that are possible.

  13. Words, Concepts, and the Geometry of Analogy

    Directory of Open Access Journals (Sweden)

    Stephen McGregor

    2016-08-01

    Full Text Available This paper presents a geometric approach to the problem of modelling the relationship between words and concepts, focusing in particular on analogical phenomena in language and cognition. Grounded in recent theories regarding geometric conceptual spaces, we begin with an analysis of existing static distributional semantic models and move on to an exploration of a dynamic approach to using high dimensional spaces of word meaning to project subspaces where analogies can potentially be solved in an online, contextualised way. The crucial element of this analysis is the positioning of statistics in a geometric environment replete with opportunities for interpretation.

  14. Analogical reasoning abilities of recovering alcoholics.

    Science.gov (United States)

    Gardner, M K; Clark, E; Bowman, M A; Miller, P J

    1989-08-01

    This study investigated analogical reasoning abilities of alcoholics who had been abstinent from alcohol for at least 1 year. Their performance was compared to that of nonalcoholic controls matched as a group for education, age, and gender. Solution times and error rates were modeled using a regression model. Results showed a nonsignificant trend for alcoholics to be faster, but more error prone, than controls. The same componential model applied to both groups, and fit them equally well. Although differences have been found in analogical reasoning ability between controls and alcoholics immediately following detoxification, we find no evidence of differences after extended periods of sobriety.

  15. Analogy in systems management: a theoretical inquiry

    Energy Technology Data Exchange (ETDEWEB)

    Silverman, B.G.

    1983-11-01

    This theoretical analysis of the intuitive and diffuse characteristics of analogical reasoning processes is the first step in a research effort intended to lead to: understanding of common (and possibly costly) errors, pitfalls, travails, and problem-solving impediments; possible recommendations for improvements to organizational structures, control and coordination processes, and management information flows, and guidelines for a generalized analogical reasoning support framework (e.g., a handbook, a knowledge bank design, and/or even a software package/artificial intelligence program). 233 references.

  16. Analysis of Recurrent Analog Neural Networks

    Directory of Open Access Journals (Sweden)

    Z. Raida

    1998-06-01

    Full Text Available In this paper, an original rigorous analysis of recurrent analog neural networks, which are built from opamp neurons, is presented. The analysis, which comes from the approximate model of the operational amplifier, reveals causes of possible non-stable states and enables to determine convergence properties of the network. Results of the analysis are discussed in order to enable development of original robust and fast analog networks. In the analysis, the special attention is turned to the examination of the influence of real circuit elements and of the statistical parameters of processed signals to the parameters of the network.

  17. Analogy Mapping Development for Learning Programming

    Science.gov (United States)

    Sukamto, R. A.; Prabawa, H. W.; Kurniawati, S.

    2017-02-01

    Programming skill is an important skill for computer science students, whereas nowadays, there many computer science students are lack of skills and information technology knowledges in Indonesia. This is contrary with the implementation of the ASEAN Economic Community (AEC) since the end of 2015 which is the qualified worker needed. This study provided an effort for nailing programming skills by mapping program code to visual analogies as learning media. The developed media was based on state machine and compiler principle and was implemented in C programming language. The state of every basic condition in programming were successful determined as analogy visualization.

  18. Design of analog integrated circuits and systems

    CERN Document Server

    Laker, Kenneth R

    1994-01-01

    This text is designed for senior or graduate level courses in analog integrated circuits or design of analog integrated circuits. This book combines consideration of CMOS and bipolar circuits into a unified treatment. Also included are CMOS-bipolar circuits made possible by BiCMOS technology. The text progresses from MOS and bipolar device modelling to simple one and two transistor building block circuits. The final two chapters present a unified coverage of sample-data and continuous-time signal processing systems.

  19. Abscisic acid analogs as chemical probes for dissection of abscisic acid responses in Arabidopsis thaliana.

    Science.gov (United States)

    Benson, Chantel L; Kepka, Michal; Wunschel, Christian; Rajagopalan, Nandhakishore; Nelson, Ken M; Christmann, Alexander; Abrams, Suzanne R; Grill, Erwin; Loewen, Michele C

    2015-05-01

    Abscisic acid (ABA) is a phytohormone known to mediate numerous plant developmental processes and responses to environmental stress. In Arabidopsis thaliana, ABA acts, through a genetically redundant family of ABA receptors entitled Regulatory Component of ABA Receptor (RCAR)/Pyrabactin Resistant 1 (PYR1)/Pyrabactin Resistant-Like (PYL) receptors comprised of thirteen homologues acting in concert with a seven-member set of phosphatases. The individual contributions of A. thaliana RCARs and their binding partners with respect to specific physiological functions are as yet poorly understood. Towards developing efficacious plant growth regulators selective for specific ABA functions and tools for elucidating ABA perception, a panel of ABA analogs altered specifically on positions around the ABA ring was assembled. These analogs have been used to probe thirteen RCARs and four type 2C protein phosphatases (PP2Cs) and were also screened against representative physiological assays in the model plant Arabidopsis. The 1'-O methyl ether of (S)-ABA was identified as selective in that, at physiologically relevant levels, it regulates stomatal aperture and improves drought tolerance, but does not inhibit germination or root growth. Analogs with the 7'- and 8'-methyl groups of the ABA ring replaced with bulkier groups generally retained the activity and stereoselectivity of (S)- and (R)-ABA, while alteration of the 9'-methyl group afforded an analog that substituted for ABA in inhibiting germination but neither root growth nor stomatal closure. Further in vitro testing indicated differences in binding of analogs to individual RCARs, as well as differences in the enzyme activity resulting from specific PP2Cs bound to RCAR-analog complexes. Ultimately, these findings highlight the potential of a broader chemical genetics approach for dissection of the complex network mediating ABA-perception, signaling and functionality within a given species and modifications in the future design

  20. High-speed and high-resolution analog-to-digital and digital-to-analog converters

    NARCIS (Netherlands)

    van de Plassche, R.J.

    1989-01-01

    Analog-to-digital and digital-to-analog converters are important building blocks connecting the analog world of transducers with the digital world of computing, signal processing and data acquisition systems. In chapter two the converter as part of a system is described. Requirements of analog

  1. Process and circuiting arrangement for the conversion of analog signals to digital signals and digital signals to analog signals

    International Nuclear Information System (INIS)

    Wintzer, K.

    1977-01-01

    Process for analog-to-digital and digital-to-analog conversion in telecommunication systems whose outstations each have an analog transmitter and an analog receiver. The invention illustrates a method of reducing the power demand of the converters at times when no conversion processes take place. (RW) [de

  2. Tumour uptake of the radiolabelled somatostatin analogue [DOTA0,TYR3]octreotide is dependent on the peptide amount

    International Nuclear Information System (INIS)

    Jong, M. de; Breeman, W.A.P.; Bernard, B.F.; Gameren, A. van; Bruin, E. de; Bakker, W.H.; Van der Pluijm, M.E.; Krenning, E.P.; Visser, T.J.; Maecke, H.R.

    1999-01-01

    Radiolabelled tumour receptor-binding peptides can be used for in vivo scintigraphic imaging. Recently, the somatostatin analogue [Tyr 3 ]octreotide (d-Phe-c(Cys-Tyr-d-Trp-Lys-Thr-Cys)-Thr(ol)) was derivatized with the chelator DOTA (tetra-azacyclododecane-tetra-acetic acid), enabling stable radiolabelling with both the high-energy beta particle-emitter yttrium-90 and the Auger electron-emitter indium-111. The thus produced radiolabelled compounds are promising for peptide receptor radionuclide therapy. Our previous in vitro and in vivo (rat) experiments with these radiolabelled compounds showed favourable binding and biodistribution characteristics with high uptake and retention in the target organs. We also demonstrated receptor-specific, time- and temperature-dependent internalization of radiolabelled [DOTA 0 ,Tyr 3 ]octreotide in somatostatin receptor subtype 2 (sst 2 )-positive rat pancreatic tumour cell lines. In this study we have investigated the effects of differences in the amount of injected peptide on tissue distribution of 111 In-labelled [DOTA 0 ,Tyr 3 ]octreotide in normal, i.e. non-tumour-bearing, and CA20948 tumour-bearing rats. This was done in order to find the amount of peptide at which the highest uptake in target tissues is achieved, and thereby to increase the potential of radionuclide therapy while simultaneously ensuring the lowest possible radiotoxicity in normal organs. Uptake of radiolabelled [DOTA 0 ,Tyr 3 ]octreotide in sst 2 -positive organs showed different bell-shaped functions of the amount of injected peptide, being highest at 0.05 (adrenals), 0.05-0.1 (pituitary and stomach) and 0.25 (pancreas) μg. Uptake in the tumour was highest at 0.5 μg injected peptide. The highest uptake was found at peptide amounts that were lower than those reported for [ 111 In-DTPA 0 ]octreotide (d-Phe-c(Cys-Phe-d-Trp-Lys-Thr-Cys)-Thr(ol), DTPA = diethylene-triamine-penta-acetic acid), consistent with the higher receptor affinity of the first compound

  3. Preliminary clinical evaluation of Somatostatin Receptor Scintigraphy (SRS) with 99mTc-EDDA/HYNIC-TATE in comparison to 111In-Octreoscan and 131 I MIBG scans

    International Nuclear Information System (INIS)

    Hubalewska, A.; Fross, K.; Staszczak, A.; Huszno, B.; Mikolajczak, R.; Gorska, A.

    2004-01-01

    Full text: Over expression of somatostatin receptors in various neuroendocrine tumours prompted development of somatostatin analogues, which after radioactive labelling, could be used in oncological diagnostics. Somatostatin Receptor Positive Tumour (Spt) imaging with 111In-DTPA-DPhe1- octreotide (111In-Octreoscan) has become a widely used diagnostic procedure in clinical nuclear medicine. However 111In as a radiolabel has several drawbacks, including limited availability, sub optimal gamma energy and high radiation burden to the patient. Technetium (99mTc) labelling of somatostatin analogues is especially attractive due to the ready availability of 99mTc from generators and its well recognised favourable imaging characteristics. HYNIC conjugated Tyr 3 -Octreotate (HYNIC-TATE) prepared in our laboratory in a dry kit form was labelled with technetium-99mTc, with tricine and EDDA used as coligands. Tyr3-octreotate differs from octreotide (OC) by more hydrophilic tyrosine in the third position and the terminal threonine, which replaced threoninol present in OC. In vitro studies using cell lines transfected with somatostatin receptors (SSTR) revealed that octreotate shows 14- 17 times better binding affinity for SSTR type 2 than does OC. It is expected to clear more rapidly from non-target tissues as a result of the carboxylic group at the C-terminal of the peptide. HYNIC has been used as bifunctional chelator in 99mTc-HYNIC-Tyr3-octreotide (TOC) by Maecke and Behe, who reported on its favourable preclinical characteristics when EDDA was used as a co-ligand. These pre-clinical data were confirmed by Decristoforo and Mather and their early clinical studies appeared recently. The new radiopharmaceutical - 99mTc-DDA/HYNICTATE was evaluated in-vitro and in-vivo in an animal model and its potential for SSTR scintigraphy was documented. In the current patient study the diagnostic usefulness of the new radiopharmaceutical was tested for detection of tumours expressing SSTR

  4. Methane. [biosynthesis from manure or analogous substance

    Energy Technology Data Exchange (ETDEWEB)

    Ducellier, G L.R.; Isman, M A

    1949-04-19

    CH/sub 4/ is produced by the fermentation of manure or analogous substances in a vat having a dome covering the vat, the lower edge of the dome being immersed in a liquid seal, and the dome being arranged to rise vertically in order to hold the CH/sub 4/ produced.

  5. Analog voicing detector responds to pitch

    Science.gov (United States)

    Abel, R. S.; Watkins, H. E.

    1967-01-01

    Modified electronic voice encoder /Vocoder/ includes an independent analog mode of operation in addition to the conventional digital mode. The Vocoder is a bandwidth compression equipment that permits voice transmission over channels, having only a fraction of the bandwidth required for conventional telephone-quality speech transmission.

  6. Invention through Form and Function Analogy

    Science.gov (United States)

    Rule, Audrey C.

    2015-01-01

    "Invention through Form and Function Analogy" is an invention book for teachers and other leaders working with youth who are involving students in the invention process. The book consists of an introduction and set of nine learning cycle formatted lessons for teaching the principles of invention through the science and engineering design…

  7. Formal analogies in physics teacher education

    DEFF Research Database (Denmark)

    Avelar Sotomaior Karam, Ricardo; Ricardo, Elio

    2012-01-01

    the exact same appearance. Coulomb’s law’s similarity with Newton’s, Maxwell’s application of fluid theory to electromagnetism and Hamilton’s optical mechanical analogy are some among many other examples. These cases illustrate the power of mathematics in providing unifying structures for physics. Despite...

  8. An iconic, analogical approach to grammaticalization

    NARCIS (Netherlands)

    Fischer, O.; Conradie, C.J.; Johl, R.; Beukes, M.; Fischer, O.; Ljungberg, C.

    2010-01-01

    This paper addresses a number of problems connected with the ‘apparatus’ used in grammaticalization theory. It will be argued that we get a better grip on what happens in processes of grammaticalization (and its ‘opposite’, lexicalization) if the process is viewed in terms of analogical processes,

  9. Analog and digital dividers for mass spectrometers

    International Nuclear Information System (INIS)

    Osipov, A.K.

    1980-01-01

    Errors of four different types of stress dividers used in statical mass-spectrometers for determination of mass number by accelerating stress are analyzed. The simplest flowsheet of the analog divider comprises operation amplifier, in the chain of the negative feedback of which a multiplication device on differential cascade is switched- in. This analog divider has high sensitivity to temperature and high error approximately 5%. Application of the multiplier on differential cascade with normalization permits to increase temperature stability and decrease the error up to 1%. Another type of the analog divider is a logarithmic divider the error of which is constant within the whole operation range and it constitutes 1-5%. The digital divider with a digital-analog transformer (DAT) has the error of +-0.015% which is determined by the error of detectors and resistance of keys in the locked state. Considered is the design of a divider based on transformation of the inlet stress into the time period. The error of the divider is determined in this case mainly by stress of the zero shift of the operation amplifier (it should be compensated) and relative threshold stability of the comparator triggering which equals (2-3)x10 -4 . It is noted that the divider with DAT application and the divider with the use of stress transformation within the time period are most perspective ones for statical mass-spectrometers [ru

  10. Analog Experiment for rootless cone eruption

    Science.gov (United States)

    Noguchi, R.; Hamada, A.; Suzuki, A.; Kurita, K.

    2017-09-01

    Rootless cone is a unique geomorphological landmark to specify igneous origin of investigated terrane, which is formed by magma-water interaction. To understand its formation mechanism we conducted analog experiment for heat-induced vesiculation by using hot syrup and sodium bicarbonate solution.

  11. SSERVI Analog Regolith Simulant Testbed Facility

    Science.gov (United States)

    Minafra, J.; Schmidt, G. K.

    2016-12-01

    SSERVI's goals include supporting planetary researchers within NASA, other government agencies; private sector and hardware developers; competitors in focused prize design competitions; and academic sector researchers. The SSERVI Analog Regolith Simulant Testbed provides opportunities for research scientists and engineers to study the effects of regolith analog testbed research in the planetary exploration field. This capability is essential to help to understand the basic effects of continued long-term exposure to a simulated analog test environment. The current facility houses approximately eight tons of JSC-1A lunar regolith simulant in a test bin consisting of a 4 meter by 4 meter area. SSERVI provides a bridge between several groups, joining together researchers from: 1) scientific and exploration communities, 2) multiple disciplines across a wide range of planetary sciences, and 3) domestic and international communities and partnerships. This testbed provides a means of consolidating the tasks of acquisition, storage and safety mitigation in handling large quantities of regolith simulant Facility hardware and environment testing scenarios include, but are not limited to the following; Lunar surface mobility, Dust exposure and mitigation, Regolith handling and excavation, Solar-like illumination, Lunar surface compaction profile, Lofted dust, Mechanical properties of lunar regolith, and Surface features (i.e. grades and rocks) Numerous benefits vary from easy access to a controlled analog regolith simulant testbed, and planetary exploration activities at NASA Research Park, to academia and expanded commercial opportunities in California's Silicon Valley, as well as public outreach and education opportunities.

  12. A physical analogy to fuzzy clustering

    DEFF Research Database (Denmark)

    Jantzen, Jan

    2004-01-01

    This tutorial paper provides an interpretation of the membership assignment in the fuzzy clustering algorithm fuzzy c-means. The membership of a data point to several clusters is shown to be analogous to the gravitational forces between bodies of mass. This provides an alternative way to explain...

  13. A high-speed analog neural processor

    NARCIS (Netherlands)

    Masa, P.; Masa, Peter; Hoen, Klaas; Hoen, Klaas; Wallinga, Hans

    1994-01-01

    Targeted at high-energy physics research applications, our special-purpose analog neural processor can classify up to 70 dimensional vectors within 50 nanoseconds. The decision-making process of the implemented feedforward neural network enables this type of computation to tolerate weight

  14. C4913 ANALOGE OG DIGITALE FILTRE

    DEFF Research Database (Denmark)

    Gaunholt, Hans

    1996-01-01

    Theese lecture notes treats the fundamental theory and the most commonly used design methods for passive- active and digital filters with special emphasis on microelectronic realizations. The lecture notes covers 75% of the material taught in the course C4913 Analog and Digital Filters...

  15. Analog circuit design automation for performance

    NARCIS (Netherlands)

    Ning, Zhen-Qiu; Ning, Zhen-Qiu; Kole, Marq; Kole, M.E.; Mouthaan, A.J.; Wallinga, Hans

    1992-01-01

    This paper describes an improved version of the program SEAS (a Simulated Evolution approach for Analog circuit Synthesis), in which an approach for selection of alternatives based on the evaluation of mutation values is developed, and design automafion for high performance comparators is covered.

  16. Hands Together! An Analog Clock Problem

    Science.gov (United States)

    Earnest, Darrell; Radtke, Susan; Scott, Siri

    2017-01-01

    In this article, the authors first present the Hands Together! task. The mathematics in this problem concerns the relationship of hour and minute durations as reflected in the oft-overlooked proportional movements of the two hands of an analog clock. The authors go on to discuss the importance of problem solving in general. They then consider…

  17. Analog subsystem for the plutonium protection system

    International Nuclear Information System (INIS)

    Arlowe, H.D.

    1978-12-01

    An analog subsystem is described which monitors certain functions in the Plutonium Protection System. Rotary and linear potentiometer output signals are digitized, as are the outputs from thermistors and container ''bulge'' sensors. This work was sponsored by the Department of Energy/Office of Safeguards and Security (DOE/OSS) as part of the overall Sandia Fixed Facility Physical Protection Program

  18. The GMO-Nanotech (Dis)Analogy?

    Science.gov (United States)

    Sandler, Ronald; Kay, W. D.

    2006-01-01

    The genetically-modified-organism (GMO) experience has been prominent in motivating science, industry, and regulatory communities to address the social and ethical dimensions of nanotechnology. However, there are some significant problems with the GMO-nanotech analogy. First, it overstates the likelihood of a GMO-like backlash against…

  19. A Mechanical Analogy for Ohm's Law.

    Science.gov (United States)

    do Couto Tavares, Milton; And Others

    1991-01-01

    A mechanical analogy between the microscopic motion of a charged carrier in an ordinary resistor and the macroscopic motion of a ball falling along a slanted board covered with a lattice of nails is introduced. The Drude model is also introduced to include the case of inelastic collisions. Computer simulation of the motion is described. (KR)

  20. Plasma analog of particle-pair production

    International Nuclear Information System (INIS)

    Tsidulko, Yu.A.; Berk, H.L.

    1996-09-01

    It is shown that the plasma axial shear flow instability satisfies the Klein-Gordon equation. The plasma instability is then shown to be analogous to spontaneous particle-pair production when a potential energy is present that is greater than twice the particle rest mass energy. Stability criteria can be inferred based on field theoretical conservation laws

  1. Performance of the Analog Moving Window Detector

    DEFF Research Database (Denmark)

    Hansen, V. Gregers

    1970-01-01

    A type of analog integrating moving window detector for use with a scanning pulse radar is examined. A performance analysis is carried out, which takes into account both the radiation pattern of the antenna and the dynamic character of the detection process due to the angular scanning...

  2. Bootstrapped Low-Voltage Analog Switches

    DEFF Research Database (Denmark)

    Steensgaard-Madsen, Jesper

    1999-01-01

    Novel low-voltage constant-impedance analog switch circuits are proposed. The switch element is a single MOSFET, and constant-impedance operation is obtained using simple circuits to adjust the gate and bulk voltages relative to the switched signal. Low-voltage (1-volt) operation is made feasible...

  3. Analog-to-digital conversion using custom CMOS analog memory for the EOS time projection chamber

    International Nuclear Information System (INIS)

    Lee, K.L.; Arthur, A.A.; Jones, R.W.; Matis, H.S.; Nakamura, M.; Kleinfelder, S.A.; Ritter, H.G.; Wienman, H.H.

    1990-01-01

    This paper describes the multiplexing scheme of custom CMOS analog memory integrated circuits, 16 channels x 256 cells, into analog to digital converters (ADC's) to handle 15,360 signal channels of a time projection, chamber detector system. Primary requirements of this system are high density, low power and large dynamic range. The analog memory device multiplexing scheme was designed to digitize the information stored in the memory cells. The digitization time of the ADC's and the settling times for the memory unit were carefully interleaved to optimize the performance and timing during the multiplexing operation. This kept the total number of ADC's, a costly and power dissipative component, to an acceptable minimum

  4. Single photon emission computed tomography procedure improves accuracy of somatostatin receptor scintigraphy in endocrine gastro-entero-pancreatic tumours

    International Nuclear Information System (INIS)

    Lebtahi, R.; Genin, R.; Rouzet, F.; Bleicner-Perez, S.; Lievre, A.; Scigliano, S.; Vialle, C.; Le Guludec, D.; Cadiot, G.; Sobhani, I.; Mignon, M.

    2005-01-01

    Somatostatin receptors scintigraphy (SRS) is a sensitive method for the detection of endocrine gastro-entero-pancreatic tumors. The aim of this study was to evaluate the sensitivity of anterior and posterior planar associated to single photon emission computerized tomography (SPECT) compared to anterior and posterior planar associated to additional lateral and oblique views in the detection of abdominal endocrine tumors. One hundred and sixty four patients with endocrine gastro-entero-pancreatic tumors were included in this study. Scintigraphic images were performed after injection of 189 ± 23 MBq of 111 In-Pentetreotide. Abdominal planar images were performed 4 h and 24 hours after injection. Abdominal SPECT was performed at 24 hours. The combination of anterior and posterior abdominal planar images with SPECT using iterative reconstruction detected significantly more tumoral sites compared to multiple planar images (298 versus 280 for the liver, p = 0.01 and 90 versus 88 for coeliac area). In particular liver lesions were better delineated on tomographic slices. The combination of 111 In-Pentetreotide SPECT with anterior and posterior planar images is more sensitive than multiple planar images to detect abdominal endocrine tumors. (author)

  5. Somatostatin-positive interneurons in the dentate gyrus of mice provide local- and long-range septal synaptic inhibition.

    Science.gov (United States)

    Yuan, Mei; Meyer, Thomas; Benkowitz, Christoph; Savanthrapadian, Shakuntala; Ansel-Bollepalli, Laura; Foggetti, Angelica; Wulff, Peer; Alcami, Pepe; Elgueta, Claudio; Bartos, Marlene

    2017-04-03

    Somatostatin-expressing-interneurons (SOMIs) in the dentate gyrus (DG) control formation of granule cell (GC) assemblies during memory acquisition. Hilar-perforant-path-associated interneurons (HIPP cells) have been considered to be synonymous for DG-SOMIs. Deviating from this assumption, we show two functionally contrasting DG-SOMI-types. The classical feedback-inhibitory HIPPs distribute axon fibers in the molecular layer. They are engaged by converging GC-inputs and provide dendritic inhibition to the DG circuitry. In contrast, SOMIs with axon in the hilus, termed hilar interneurons (HILs), provide perisomatic inhibition onto GABAergic cells in the DG and project to the medial septum. Repetitive activation of glutamatergic inputs onto HIPP cells induces long-lasting-depression (LTD) of synaptic transmission but long-term-potentiation (LTP) of synaptic signals in HIL cells. Thus, LTD in HIPPs may assist flow of spatial information from the entorhinal cortex to the DG, whereas LTP in HILs may facilitate the temporal coordination of GCs with activity patterns governed by the medial septum.

  6. Somatostatin is required for masculinization of growth hormone–regulated hepatic gene expression but not of somatic growth

    Science.gov (United States)

    Low, Malcolm J.; Otero-Corchon, Veronica; Parlow, Albert F.; Ramirez, Jose L.; Kumar, Ujendra; Patel, Yogesh C.; Rubinstein, Marcelo

    2001-01-01

    Pulsatile growth hormone (GH) secretion differs between males and females and regulates the sex-specific expression of cytochrome P450s in liver. Sex steroids influence the secretory dynamics of GH, but the neuroendocrine mechanisms have not been conclusively established. Because periventricular hypothalamic somatostatin (SST) expression is greater in males than in females, we generated knockout (Smst–/–) mice to investigate whether SST peptides are necessary for sexually differentiated GH secretion and action. Despite marked increases in nadir and median plasma GH levels in both sexes of Smst–/– compared with Smst+/+ mice, the mutant mice had growth curves identical to their sibling controls and retained a normal sexual dimorphism in weight and length. In contrast, the liver of male Smst–/– mice was feminized, resulting in an identical profile of GH-regulated hepatic mRNAs between male and female mutants. Male Smst-/- mice show higher expression of two SST receptors in the hypothalamus and pituitary than do females. These data indicate that SST is required to masculinize the ultradian GH rhythm by suppressing interpulse GH levels. In the absence of SST, male and female mice exhibit similarly altered plasma GH profiles that eliminate sexually dimorphic liver function but do not affect dimorphic growth. PMID:11413165

  7. Amelioration of improper differentiation of somatostatin-positive interneurons by triiodothyronine in a growth-retarded hypothyroid mouse strain.

    Science.gov (United States)

    Uchida, Katsuya; Taguchi, Yusuke; Sato, Chika; Miyazaki, Hidetaka; Kobayashi, Kenichi; Kobayashi, Tetsuya; Itoi, Keiichi

    2014-01-24

    Thyroid hormone (TH) plays an important role in brain development, and TH deficiency during pregnancy or early postnatal periods leads to neurological disorders such as cretinism. Hypothyroidism reduces the number of parvalbumin (PV)-positive interneurons in the neocortex and hippocampus. Here we used a mouse strain (growth-retarded; grt) that shows growth retardation and hypothyroidism to examine whether somatostatin (Sst)-positive interneurons that are generated from the same pool of neural progenitor cells as PV-positive cells are also altered by TH deficiency. The number of PV-positive interneurons was significantly decreased in the neocortex and hippocampus of grt mice as compared with normal control mice. In contrast to the decrease in the number of PV neurons, the number of Sst-positive interneurons in grt mice was increased in the stratum oriens of the hippocampus and the hilus of the dentate gyrus, although their number was unchanged in the neocortex. These changes were reversed by triiodothyronine administration from postnatal day (PD) 0 to 20. TH supplementation that was initiated after PD21 did not, however, affect the number of PV- or Sst-positive cells. These results suggest that during the first three postnatal weeks, TH may be critical for the generation of subpopulations of interneurons. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  8. PET/CT imaging of human somatostatin receptor 2 (hsstr2) as reporter gene for gene therapy

    International Nuclear Information System (INIS)

    Hofmann, M.; Gazdhar, A.; Weitzel, T.; Schmid, R.; Krause, T.

    2006-01-01

    Localized information on region-selective gene expression in small animals is widely obtained by use of reporter genes inducing light emission. Using these reporter genes for imaging deep inside the human body fluorescent probes are hindered by attenuation, scattering and possible fluorescence quenching. This can be overcome by use of radio-peptide receptors as reporter genes. Therefore, the feasibility of the somatostatin receptor 2 expression vector system for expression imaging was checked against a control vector containing luciferase gene. For in vivo transduction of vector DNA into the rat forelimb muscles the in vivo electroporation technique was chosen because of its high regio-selectivity. The gene expression was imaged by high-sensitive CCD camera (luciferase activity) and by PET/CT using a Ga-68-DOTATOC as radio peptide probe. The relative sstr2 expression was enhanced by gene transduction at maximum to a factor of 15. The PET/CT images could be fully quantified. The above demonstrated feasibility of radio-peptide PET/CT reporter gene imaging may serve in the future as a tool for full quantitative understanding of regional gene expression, especially in large animals and humans

  9. PET/CT imaging of human somatostatin receptor 2 (hsstr2) as reporter gene for gene therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hofmann, M. [Molecular Imaging and Therapy Group (MIT-Bern), Clinic of Nuclear Medicine, Inselspital, Medical School Bern (Switzerland)]. E-mail: Michael.Hofmann@insel.ch; Gazdhar, A. [Division of Pulmonary Medicine, University Hospital Bern (Switzerland); Weitzel, T. [Molecular Imaging and Therapy Group (MIT-Bern), Clinic of Nuclear Medicine, Inselspital, Medical School Bern (Switzerland); Schmid, R. [Division of Thoracic Surgery, University Hospital Bern (Switzerland); Krause, T. [Molecular Imaging and Therapy Group (MIT-Bern), Clinic of Nuclear Medicine, Inselspital, Medical School Bern (Switzerland)

    2006-12-20

    Localized information on region-selective gene expression in small animals is widely obtained by use of reporter genes inducing light emission. Using these reporter genes for imaging deep inside the human body fluorescent probes are hindered by attenuation, scattering and possible fluorescence quenching. This can be overcome by use of radio-peptide receptors as reporter genes. Therefore, the feasibility of the somatostatin receptor 2 expression vector system for expression imaging was checked against a control vector containing luciferase gene. For in vivo transduction of vector DNA into the rat forelimb muscles the in vivo electroporation technique was chosen because of its high regio-selectivity. The gene expression was imaged by high-sensitive CCD camera (luciferase activity) and by PET/CT using a Ga-68-DOTATOC as radio peptide probe. The relative sstr2 expression was enhanced by gene transduction at maximum to a factor of 15. The PET/CT images could be fully quantified. The above demonstrated feasibility of radio-peptide PET/CT reporter gene imaging may serve in the future as a tool for full quantitative understanding of regional gene expression, especially in large animals and human000.

  10. Somatostatin does not attenuate intestinal injury in dextran sodium sulphate-induced subacute colitis

    Directory of Open Access Journals (Sweden)

    J. D. van Bergeijk

    1998-01-01

    Full Text Available From several in vitro and in vivo studies involvement of som atostatin (SMS in intestinal inflammation emerge. Acute colitis induced in rats is attenuated by the long-acting SMS analogue octreotide. We studied the potential beneficial effect of SMS on non-acute experimental colitis. BALB/c mice received either saline, SMS-14 (36 or 120 μg daily or octreotide (3 μg daily subcutaneously delivered by implant osmotic pumps. A non-acute colitis was induced by administration of dextran sodium sulphate (DSS 10% in drinking water during 7 days. DSS evoked a mild, superficial pancolitis, most characterized by mucosal ulceration and submucosal influx of neutrophils. Neither SMS-14 nor octreotide reduced mucosal inflammatory score or macroscopical disease activity, although reduction of intestinal levels of interleukin1 β (IL-1 β, IL-6 and IL-10 during DSS was augmented both by SMS and octreotide. A slight increase of neutrophil influx was seen during SMS administration in animals not exposed to DSS. In conclusion, SMS or its long-acting analogue did not reduce intestinal inflammation in non-acute DSS-induced colitis. According to the cytokine profile observed, SMS-14 and octreotide further diminished the reduction of intestinal macrophage and Th2 lymphocyte activity.

  11. Multilateral Research Opportunities in Ground Analogs

    Science.gov (United States)

    Corbin, Barbara J.

    2015-01-01

    The global economy forces many nations to consider their national investments and make difficult decisions regarding their investment in future exploration. International collaboration provides an opportunity to leverage other nations' investments to meet common goals. The Humans In Space Community shares a common goal to enable safe, reliable, and productive human space exploration within and beyond Low Earth Orbit. Meeting this goal requires efficient use of limited resources and International capabilities. The International Space Station (ISS) is our primary platform to conduct microgravity research targeted at reducing human health and performance risks for exploration missions. Access to ISS resources, however, is becoming more and more constrained and will only be available through 2020 or 2024. NASA's Human Research Program (HRP) is actively pursuing methods to effectively utilize the ISS and appropriate ground analogs to understand and mitigate human health and performance risks prior to embarking on human exploration of deep space destinations. HRP developed a plan to use ground analogs of increasing fidelity to address questions related to exploration missions and is inviting International participation in these planned campaigns. Using established working groups and multilateral panels, the HRP is working with multiple Space Agencies to invite International participation in a series of 30- day missions that HRP will conduct in the US owned and operated Human Exploration Research Analog (HERA) during 2016. In addition, the HRP is negotiating access to Antarctic stations (both US and non-US), the German :envihab and Russian NEK facilities. These facilities provide unique capabilities to address critical research questions requiring longer duration simulation or isolation. We are negotiating release of international research opportunities to ensure a multilateral approach to future analog research campaigns, hoping to begin multilateral campaigns in the

  12. Using Visual Analogies To Teach Introductory Statistical Concepts

    Directory of Open Access Journals (Sweden)

    Jessica S. Ancker

    2017-07-01

    Full Text Available Introductory statistical concepts are some of the most challenging to convey in quantitative literacy courses. Analogies supplemented by visual illustrations can be highly effective teaching tools. This literature review shows that to exploit the power of analogies, teachers must select analogies familiar to the audience, explicitly link the analog with the target concept, and avert misconceptions by explaining where the analogy fails. We provide guidance for instructors and a series of visual analogies for use in teaching medical and health statistics.

  13. Analogical reasoning in children with specific language impairment: Evidence from a scene analogy task.

    Science.gov (United States)

    Krzemien, Magali; Jemel, Boutheina; Maillart, Christelle

    2017-01-01

    Analogical reasoning is a human ability that maps systems of relations. It develops along with relational knowledge, working memory and executive functions such as inhibition. It also maintains a mutual influence on language development. Some authors have taken a greater interest in the analogical reasoning ability of children with language disorders, specifically those with specific language impairment (SLI). These children apparently have weaker analogical reasoning abilities than their aged-matched peers without language disorders. Following cognitive theories of language acquisition, this deficit could be one of the causes of language disorders in SLI, especially those concerning productivity. To confirm this deficit and its link to language disorders, we use a scene analogy task to evaluate the analogical performance of SLI children and compare them to controls of the same age and linguistic abilities. Results show that children with SLI perform worse than age-matched peers, but similar to language-matched peers. They are more influenced by increased task difficulty. The association between language disorders and analogical reasoning in SLI can be confirmed. The hypothesis of limited processing capacity in SLI is also being considered.

  14. Analog data transmission via fiber optics

    International Nuclear Information System (INIS)

    Cisneros, E.L.; Burgueno, G.F.

    1986-10-01

    In the SLAC Linear Collider Detector (SLD), as in most high-energy particle detectors, the electromagnetic noise environment is the limiting factor in electronic readout performance. Front-end electronics are particulary susceptible to electromagnetic interference (EMI), and great care has been taken to minimize its effects. The transfer of preprocessed analog signals from the detector environs, to the remote digital processing electronics, by conventional means (via metal conductors), may ultimately limit the performance of the system. Because it is highly impervious to EMI and ground loops, a fiber-optic medium has been chosen for the transmission of these signals. This paper describes several fiber-optic transmission schemes which satisfy the requirements of the SLD analog data transmission

  15. Analog data transmission via fiber optics

    International Nuclear Information System (INIS)

    Cisneros, E.L.; Burgueno, G.F.

    1987-01-01

    In the SLAC Linear Collider Detector (SLD), as in most high-energy particle detectors, the electromagnetic noise environment is the limiting factor in electronic readout performance. Front-end electronics are particularly susceptible to electromagnetic interference (EMI), and great care has been taken to minimize its effects. The transfer of preprocessed analog signals from the detector environs, to the remote digital processing electronics, by conventional means (via metal conductors), may ultimately limit the performance of the system. Because it is highly impervious to EMI and ground loops, a fiber-optic medium has been chosen for the transmission of these signals. This paper describes several fiber-optic transmission schemes which satisfy the requirements of the SLD analog data transmission

  16. An analogy strategy for transformation optics

    International Nuclear Information System (INIS)

    Yao, Kan; Liu, Yongmin; Chen, Huanyang; Jiang, Xunya

    2014-01-01

    We introduce an analogy strategy to design transformation optical devices. Based on the similarities between field lines in different physical systems, the trajectories of light can be intuitively determined to curve in a gentle manner, and the resulting materials are isotropic and nonmagnetic. Furthermore, the physical meaning of the analogue problems plays a key role in the removal of dielectric singularities. We illustrate this approach by creating two designs of carpet cloak and a collimating lens as representative examples in two- and three-dimensional spaces, respectively. The analogy strategy not only reveals the intimate connections between different physical disciplines, such as optics, fluid mechanics and electrostatics, but also provides a heuristic pathway to designing advanced photonic systems

  17. The optical analogy for vector fields

    Science.gov (United States)

    Parker, E. N. (Editor)

    1991-01-01

    This paper develops the optical analogy for a general vector field. The optical analogy allows the examination of certain aspects of a vector field that are not otherwise readily accessible. In particular, in the cases of a stationary Eulerian flow v of an ideal fluid and a magnetostatic field B, the vectors v and B have surface loci in common with their curls. The intrinsic discontinuities around local maxima in absolute values of v and B take the form of vortex sheets and current sheets, respectively, the former playing a fundamental role in the development of hydrodyamic turbulence and the latter playing a major role in heating the X-ray coronas of stars and galaxies.

  18. High resolution tomography using analog coding

    International Nuclear Information System (INIS)

    Brownell, G.L.; Burnham, C.A.; Chesler, D.A.

    1985-01-01

    As part of a 30-year program in the development of positron instrumentation, the authors have developed a high resolution bismuth germanate (BGO) ring tomography (PCR) employing 360 detectors and 90 photomultiplier tubes for one plane. The detectors are shaped as trapezoid and are 4 mm wide at the front end. When assembled, they form an essentially continuous cylindrical detector. Light from a scintillation in the detector is viewed through a cylindrical light pipe by the photomultiplier tubes. By use of an analog coding scheme, the detector emitting light is identified from the phototube signals. In effect, each phototube can identify four crystals. PCR is designed as a static device and does not use interpolative motion. This results in considerable advantage when performing dynamic studies. PCR is the positron tomography analog of the γ-camera widely used in nuclear medicine

  19. Analog fault diagnosis by inverse problem technique

    KAUST Repository

    Ahmed, Rania F.

    2011-12-01

    A novel algorithm for detecting soft faults in linear analog circuits based on the inverse problem concept is proposed. The proposed approach utilizes optimization techniques with the aid of sensitivity analysis. The main contribution of this work is to apply the inverse problem technique to estimate the actual parameter values of the tested circuit and so, to detect and diagnose single fault in analog circuits. The validation of the algorithm is illustrated through applying it to Sallen-Key second order band pass filter and the results show that the detecting percentage efficiency was 100% and also, the maximum error percentage of estimating the parameter values is 0.7%. This technique can be applied to any other linear circuit and it also can be extended to be applied to non-linear circuits. © 2011 IEEE.

  20. Optimal neural computations require analog processors

    Energy Technology Data Exchange (ETDEWEB)

    Beiu, V.

    1998-12-31

    This paper discusses some of the limitations of hardware implementations of neural networks. The authors start by presenting neural structures and their biological inspirations, while mentioning the simplifications leading to artificial neural networks. Further, the focus will be on hardware imposed constraints. They will present recent results for three different alternatives of parallel implementations of neural networks: digital circuits, threshold gate circuits, and analog circuits. The area and the delay will be related to the neurons` fan-in and to the precision of their synaptic weights. The main conclusion is that hardware-efficient solutions require analog computations, and suggests the following two alternatives: (i) cope with the limitations imposed by silicon, by speeding up the computation of the elementary silicon neurons; (2) investigate solutions which would allow the use of the third dimension (e.g. using optical interconnections).