Pilocarpine effect on dose rate of salivary gland in differentiated thyroid carcinoma patients treated with radioiodine.

PubMed

Haghighatafshar, Mahdi; Ghaedian, Mehrnaz; Etemadi, Zahra; Entezarmahdi, Seyed M; Ghaedian, Tahereh

2018-05-01

Although different methods have been suggested on reducing salivary gland radiation after radioiodine administration, an effective preventive or therapeutic measure is still up for debate. The aim of this study was to evaluate the effect of pilocarpine, as a sialagogue drug on the radioiodine content of the salivary gland, and radioiodine-induced symptoms of salivary gland dysfunction. Patients who were referred for radioiodine therapy were randomized into pilocarpine and placebo groups. The patients as well as the nurse who administered the tablets, and the specialist who analyzed the images, were all unaware of the patients' group. Anterior and posterior planar images including that of both the head and neck were obtained 2, 6, 12, 24, and 48 h after the administration of radioiodine in all patients, and round regions of interest were drawn for both left and right parotid glands, with a rectangular region of interest in the region of the cerebrum as background. All patients were interrogated once, 6 months after radioiodine administration, by a phone call for subjective evaluation of symptoms related to salivary gland damage. There was no significant difference between the two groups with regard to the mean age, sex, and initial iodine activity. The geometric mean of background-corrected count per administered dose and acquisition time was calculated for the bilateral parotid glands. This normalized parotid count showed a significant reduction in net parotid count in both groups during the first 48 h after radioiodine administration. However, no significant difference was found between the groups according to the amount and pattern of dose reduction in this time period. This study revealed that pilocarpine had no significant effect on the radioiodine content of parotid glands during the first 48 h after radioiodine administration. No significant difference was found in the incidence of symptoms between the two groups treated with placebo and pilocarpine.

Local reactions to radioiodine in the treatment of thyroid cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burmeister, L.A.; du Cret, R.P.; Mariash, C.N.

1991-02-01

The purpose of this study is to compare the rate of local complications resulting from radioiodine ablation of thyroid cancer in patients with a residual intact thyroid lobe to that in patients who had more extensive surgical treatment prior to radioiodine administration. We retrospectively studied 59 patients who had received 131I between 1979 and 1989. The patients were divided into two groups, depending on the extent of their previous surgical thyroid excision. Group 1 comprised 10 patients with a lobectomy or hemithyroidectomy before the ablative radioiodine dose, and Group 2 comprised 49 patients with more extensive thyroid excision (near-total ormore » subtotal thyroidectomy) before the radioiodine treatment. Sixty percent of the 10 patients in Group 1 experienced some degree of neck pain or tenderness following radioiodine ablation of their residual thyroid. In one case, the local reaction was very severe and accompanied by the development of transient hyperthyroidism. There was only a 6% local complication rate in the patients who had undergone more extensive thyroid excision before ablative therapy (p less than 0.001), and none had a severe reaction. Patients with only unilateral surgical excision before radioiodine therapy have a higher rate of local complications than do patients treated with more extensive surgery prior to radioiodine ablation. If radioiodine is to be employed in such patients, they should be informed of this possible complication. Since evidence supports a dose effect in the pathogenesis of the complications, we recommend using a dose of less than 30 mCi for the initial ablation in these patients even though it may be necessary to repeat this dose to complete thyroid ablation.« less

[Graves' disease nd toxic nodular goiter--radioiodine therapy].

PubMed

Schicha, H; Dietlein, M

2002-04-01

At the 15th conference on the human thyroid in Heidelberg in 2001 the following aspects of the radioiodine therapy of benign thyroid disorders were presented: General strategies for therapy of benign thyroid diseases, criterions for conservative or definitive treatment of hyperthyroidism as first line therapy and finally preparation, procedural details, results, side effects, costs and follow-up care of radioiodine therapy as well as legal guidelines for hospitalization in Germany. The diagnosis Graves' hyperthyroidism needs the decision, if rather a conservative treatment or if primary radioiodine therapy is the best therapeutic approach. In the USA 70-90% of these patients are treated with radioiodine as first line therapy, whereas in Germany the conservative therapy for 1-1.5 years is recommended for 90%. This review describes subgroups of patients with Graves' disease showing a higher probability to relapse after conservative treatment. Comparing benefits, adverse effects, costs, and conveniences of both treatment strategies the authors conclude that radioiodine therapy should be preferred as first line therapy in 60-70% of the patients with Graves' hyperthyroidism.

Variants and pitfalls on radioiodine scans in pediatric patients with differentiated thyroid carcinoma.

PubMed

Mostafa, Mohamed; Vali, Reza; Chan, Jeffrey; Omarkhail, Yusuaf; Shammas, Amer

2016-10-01

Potentially false-positive findings on radioiodine scans in children with differentiated thyroid carcinoma can mimic functioning thyroid tissue and functioning thyroid carcinomatous tissue. Such false-positive findings comprise variants and pitfalls that can vary slightly in children as compared with adults. To determine the patterns and frequency of these potential false-positive findings on radioiodine scans in children with differentiated thyroid carcinoma. We reviewed a total of 223 radioiodine scans from 53 pediatric patients (mean age 13.3 years, 37 girls) with differentiated thyroid carcinoma. Focal or regional activity that likely did not represent functioning thyroid tissue or functioning thyroid carcinomatous tissue were categorized as variants or pitfalls. The final diagnosis was confirmed by reviewing the concurrent and follow-up clinical data, correlative ultrasonography, CT scanning, serum thyroglobulin and antithyroglobulin antibody levels. We calculated the frequency of these variants and pitfalls from diagnostic and post-therapy radioiodine scans. The most common variant on the radioiodine scans was the thymic activity (24/223, 10.8%) followed by the cardiac activity (8/223, 3.6%). Salivary contamination and star artifact, caused by prominent thyroid remnant, were the most important observed pitfalls. Variants and pitfalls that mimic functioning thyroid tissue or functioning thyroid carcinomatous tissue on radioiodine scan in children with differentiated thyroid carcinoma are not infrequent, but they decrease in frequency on successive radioiodine scans. Potential false-positive findings can be minimized with proper knowledge of the common variants and pitfalls in children and correlation with clinical, laboratory and imaging data.

The impurity of radioiodinated triolein

PubMed Central

Kennedy, J. A.; Kinloch, J. D.

1964-01-01

Commercially supplied radioiodinated triolein has been shown by thin-layer chromatography and silicic acid column chromatography to contain impurities, consisting mainly of diglycerides and monoglycerides, but also a small amount of free fatty acid. The effect of these impurities on the radioiodinated triolein absorption test requires further investigation. Images PMID:14149942

Radioiodine therapy versus antithyroid drugs in Graves' disease: a meta-analysis of randomized controlled trials.

PubMed

Wang, Junqi; Qin, Lan

2016-06-27

This meta-analysis was performed to compare radioiodine therapy with antithyroid drugs in terms of clinical outcomes, including development or worsening of ophthalmopathy, hyperthyroid cure rate, hypothyroidism, relapse rate and adverse events. Randomized controlled trials (RCTs) published in PubMed, Embase, Web of Science, SinoMed and National Knowledge Infrastructure, China, were systematically reviewed to compare the effects of radioiodine therapy with antithyroid drugs in patients with Graves' disease. Results were expressed as risk ratio with 95% confidence intervals (CIs) and weighted mean differences with 95% CIs. Pooled estimates were performed using a fixed-effects model or random-effects model, depending on the heterogeneity among studies. 17 RCTs involving 4024 patients met the inclusion criteria and were included. Results showed that radioiodine treatment has increased risk in new ophthalmopathy, development or worsening of ophthalmopathy and hypothyroidism. Whereas, compared with antithyroid drugs, radioiodine treatment seems to have a higher hyperthyroid cure rate, lower recurrence rate and lower incidence of adverse events. Radioiodine therapy is associated with a higher hyperthyroid cure rate and lower relapse rate compared with antithyroid drugs. However, it also increases the risk of ophthalmopathy and hypothyroidism. Considering that antithyroid drug treatment can be associated with unsatisfactory control of hyperthyroidism, we would recommend radioiodine therapy as the treatment of choice for patients with Graves' disease.

Modulation of thyroidal radioiodide uptake by oncological pipeline inhibitors and Apigenin

PubMed Central

Lakshmanan, Aparna; Scarberry, Daniel; Green, Jill A.; Zhang, Xiaoli; Selmi-Ruby, Samia; Jhiang, Sissy M.

2015-01-01

Targeted radioiodine therapy for thyroid cancer is based on selective stimulation of Na+/I− Symporter (NIS)-mediated radioactive iodide uptake (RAIU) in thyroid cells by thyrotropin. Patients with advanced thyroid cancer do not benefit from radioiodine therapy due to reduced or absent NIS expression. To identify inhibitors that can be readily translated into clinical care, we examined oncological pipeline inhibitors targeting Akt, MEK, PI3K, Hsp90 or BRAF in their ability to increase RAIU in thyroid cells expressing BRAFV600E or RET/PTC3 oncogene. Our data showed that (1) PI3K inhibitor GDC-0941 outperformed other inhibitors in RAIU increase mainly by decreasing iodide efflux rate to a great extent; (2) RAIU increase by all inhibitors was extensively reduced by TGF-β, a cytokine secreted in the invasive fronts of thyroid cancers; (3) RAIU reduction by TGF-β was mainly mediated by NIS reduction and could be reversed by Apigenin, a plant-derived flavonoid; and (4) In the presence of TGF-β, GDC-0941 with Apigenin co-treatment had the highest RAIU level in both BRAFV600E expressing cells and RET/PTC3 expressing cells. Taken together, Apigenin may serve as a dietary supplement along with small molecule inhibitors to improve radioiodine therapeutic efficacy on invasive tumor margins thereby minimizing future metastatic events. PMID:26397139

Effects of antithyroid drugs on radioiodine treatment: systematic review and meta-analysis of randomised controlled trials.

PubMed

Walter, Martin A; Briel, Matthias; Christ-Crain, Mirjam; Bonnema, Steen J; Connell, John; Cooper, David S; Bucher, Heiner C; Müller-Brand, Jan; Müller, Beat

2007-03-10

To determine the effect of adjunctive antithyroid drugs on the risk of treatment failure, hypothyroidism, and adverse events after radioiodine treatment. Meta-analysis. Electronic databases (Cochrane central register of controlled trials, Medline, Embase) searched to August 2006 and contact with experts. Review methods Three reviewers independently assessed trial eligibility and quality. Pooled relative risks for treatment failure and hypothyroidism after radioiodine treatment with and without adjunctive antithyroid drugs were calculated with a random effects model. We identified 14 relevant randomised controlled trials with a total of 1306 participants. Adjunctive antithyroid medication was associated with an increased risk of treatment failure (relative risk 1.28, 95% confidence interval 1.07 to 1.52; P=0.006) and a reduced risk for hypothyroidism (0.68, 0.53 to 0.87; P=0.006) after radioiodine treatment. We found no difference in summary estimates for the different antithyroid drugs or for whether antithyroid drugs were given before or after radioiodine treatment. Antithyroid drugs potentially increase rates of failure and reduce rates of hypothyroidism if they are given in the week before or after radioiodine treatment, respectively.

Both α and β Subunits of Human Choriogonadotropin Photoaffinity Label the Hormone Receptor

NASA Astrophysics Data System (ADS)

Ji, Inhae; Ji, Tae H.

1981-09-01

It has been shown that a photoactivable derivative of human choriogonadotropin (hCG) labels the lutropin receptor on porcine granulosa cells [Ji, I. & Ji, T. H. (1980) Proc. Natl. Acad. Sci. USA 77, 7167-7170]. In an attempt to identify which of the hCG subunits labeled the receptor, three sets of different hCG derivatives were prepared. In the first set, hCG was coupled to the N-hydroxysuccinimide ester of 4-azidobenzoylglycine and radioiodinated. In the second set, only one of the subunits was radioiodinated, but both subunits were allowed to react with the reagent. In the third set, both the reagent and [125I]iodine were coupled to only one of the subunits. The binding activity of each hormone derivative was comparable to that of 125I-labeled hCG. After binding of these hormone derivatives to the granulosa cell surface, they were photolyzed. After solubilization, autoradiographs of sodium dodecyl sulfate/polyacrylamide gels of each sample revealed a number of labeled bands; the hCG derivatives containing 125I-labeled alpha subunit produced four bands (molecular weights 120,000 +/- 6,000, 96,000 +/- 5,000, 76,000 +/- 4,000, and 73,000 +/- 4,000) and those containing 125I-labeled beta subunit produced three bands (molecular weights 106,000 +/- 6,000, 88,000 +/- 5,000, and 83,000 +/- 4,000). Results were the same when the hormone-receptor complexes were solubilized in 0.5% Triton X-100 and then photolyzed or when the hormone was derivatized with a family of reagents having arms of various lengths. We conclude that both the alpha subunit and the beta subunit of hCG photoaffinity labeled certain membrane polypeptides and that these polypeptides are related to the hormone receptor.

Radioiodine therapy versus antithyroid drugs in Graves' disease: a meta-analysis of randomized controlled trials

PubMed Central

Qin, Lan

2016-01-01

Objective: This meta-analysis was performed to compare radioiodine therapy with antithyroid drugs in terms of clinical outcomes, including development or worsening of ophthalmopathy, hyperthyroid cure rate, hypothyroidism, relapse rate and adverse events. Methods: Randomized controlled trials (RCTs) published in PubMed, Embase, Web of Science, SinoMed and National Knowledge Infrastructure, China, were systematically reviewed to compare the effects of radioiodine therapy with antithyroid drugs in patients with Graves' disease. Results were expressed as risk ratio with 95% confidence intervals (CIs) and weighted mean differences with 95% CIs. Pooled estimates were performed using a fixed-effects model or random-effects model, depending on the heterogeneity among studies. Results: 17 RCTs involving 4024 patients met the inclusion criteria and were included. Results showed that radioiodine treatment has increased risk in new ophthalmopathy, development or worsening of ophthalmopathy and hypothyroidism. Whereas, compared with antithyroid drugs, radioiodine treatment seems to have a higher hyperthyroid cure rate, lower recurrence rate and lower incidence of adverse events. Conclusion: Radioiodine therapy is associated with a higher hyperthyroid cure rate and lower relapse rate compared with antithyroid drugs. However, it also increases the risk of ophthalmopathy and hypothyroidism. Advances in knowledge: Considering that antithyroid drug treatment can be associated with unsatisfactory control of hyperthyroidism, we would recommend radioiodine therapy as the treatment of choice for patients with Graves' disease. PMID:27266544

Radioiodine therapy versus antithyroid medications for Graves' disease.

PubMed

Ma, Chao; Xie, Jiawei; Wang, Hui; Li, Jinsong; Chen, Suyun

2016-02-18

Graves' disease is the most common cause of hyperthyroidism. Both antithyroid medications and radioiodine are commonly used treatments but their frequency of use varies between regions and countries. Despite the commonness of the diagnosis, any possible differences between the two treatments with respect to long-term outcomes remain unknown. To assess the effects of radioiodine therapy versus antithyroid medications for Graves' disease. We performed a systematic literature search in the Cochrane Library, MEDLINE and EMBASE and the trials registers ICTRP Search Portal and ClinicalTrials.gov. The date of the last search was September 2015 for all databases. Randomised controlled trials (RCTs) comparing the effects of radioiodine therapy versus antithyroid medications for Graves' disease with at least two years follow-up. Two authors independently screened titles and abstracts for relevance. One author carried out screening for inclusion, data extraction and 'Risk of bias' assessment and a second author checked this. We presented data not suitable for meta-analysis as descriptive data. We analysed the overall quality of evidence utilising the GRADE instrument. We included two RCTs involving 425 adult participants with Graves' disease in this review. Altogether 204 participants were randomised to radioiodine therapy and 221 to methimazole therapy. A single dose of radioiodine was administered. The duration of methimazole medication was 18 months. The period of follow-up was at least two years, depending on the outcome measured. For most outcome measures risk of bias was low; for the outcomes health-related quality of life as well as development and worsening of Graves' ophthalmopathy risks of performance bias and detection bias were high in at least one of the two RCTs.Health-related quality of life appeared to be similar in the radioiodine and methimazole treatment groups, however no quantitative data were reported (425 participants; 2 trials; low quality evidence). The development and worsening of Graves' ophthalmopathy was observed in 76 of 202 radioiodine-treated participants (38%) and in 40 of 215 methimazole-treated participants (19%): risk ratio (RR) 1.94 (95% confidence interval (CI) 1.40 to 2.70); 417 participants; 2 trials; low quality evidence. A total of 35% to 56% of radioiodine-treated participants and 42% of participants treated with methimazole were smokers, which is associated with the risk of worsening or development of Graves' ophthalmopathy. Euthyroidism was not achieved by any participant being treated with radioiodine compared with 64/68 (94%) of participants after methimazole treatment (112 participants; 1 trial). In this trial thyroxine therapy was not introduced early in both treatment arms to avoid hypothyroidism. Recurrence of hyperthyroidism (relapse) in favour of radioiodine treatment showed a RR of 0.20 (95% CI 0.01 to 2.66); P value = 0.22; 417 participants; 2 trials; very low quality evidence. Heterogeneity was high (I² = 91%) and the RRs were 0.61 or 0.06 with non-overlapping CIs. Adverse events other than development of worsening of Graves' ophthalmopathy for radioiodine therapy were hypothyroidism (39 of 41 participants (95%) compared with 0% of participants receiving methimazole, however thyroxine treatment to avoid hypothyroidism was not introduced early in the radioiodine group - 104 participants; 1 trial; very low quality evidence) and drug-related adverse events for methimazole treatment (23 of 215 participants (11%) reported adverse effects likely related to methimazole therapy - 215 participants; 2 trials; very low quality evidence). The outcome measures all-cause mortality and bone mineral density were not reported in the included trials. One trial (174 participants) reported socioeconomic effects: costs based on the official hospital reimbursement system in Sweden for patients without relapse and methimazole treatment were USD 1126/1164 (young/older methimazole group) and for radioiodine treatment USD 1862. Costs for patients with relapse and methimazole treatment were USD 2284/1972 (young/older methimazole group) and for radioiodine treatment USD 2760. The only antithyroid drug investigated in the two included trials was methimazole, which might limit the applicability of our findings with regard to other compounds such as propylthiouracil. Results from two RCTs suggest that radioiodine treatment is associated with an increased risk of Graves' ophthalmopathy. Our findings suggest some benefit from radioiodine treatment for recurrence of hyperthyroidism (relapse) but there is uncertainty about the magnitude of the effect size.

Calculation of Blood Dose in Patients Treated With 131I Using MIRD, Imaging, and Blood Sampling Methods

PubMed Central

Piruzan, Elham; Haghighatafshar, Mahdi; Faghihi, Reza; Entezarmahdi, Seyed Mohammad

2016-01-01

Abstract Radioiodine therapy is known as the most effective treatment of differentiated thyroid carcinoma (DTC) to ablate remnant thyroid tissue after surgery. In patients with DTC treated with radioiodine, internal radiation dosimetry of radioiodine is useful for radiation risk assessment. The aim of this study is to describe a method to estimate the absorbed dose to the blood using medical internal radiation dosimetry methods. In this study, 23 patients with DTC with different administrated activities, 3.7, 4.62, and 5.55 GBq after thyroidectomy, were randomly selected. Blood dosimetry of treated patients was performed with external whole body counting using a dual-head gamma camera imaging device and also with blood sample activity measurements using a dose calibrator. Absorbed dose to the blood was measured at 2, 6, 12, 24, 48, and 96 hours after the administration of radioiodine with the 2 methods. Based on the results of whole body counting and blood sample activity dose rate measurements, 96 hours after administration of 3.7, 4.62, and 5.55 GBq of radioiodine, absorbed doses to patients’ blood were 0.65 ± 0.20, 0.67 ± 0.18, 0.79 ± 0.51 Gy, respectively. Increasing radioiodine activity from 3.7 to 5.55 GBq increased blood dose significantly, while there was no significant difference in blood dose between radioiodine dosages of 3.7 and 4.62 GBq. Our results revealed a significant correlation between the blood absorbed dose and blood sample activity and between the blood absorbed dose and whole body counts 24 to 48 hours after the administration of radioiodine. PMID:26986171

Calculation of Blood Dose in Patients Treated With 131I Using MIRD, Imaging, and Blood Sampling Methods.

PubMed

Piruzan, Elham; Haghighatafshar, Mahdi; Faghihi, Reza; Entezarmahdi, Seyed Mohammad

2016-03-01

Radioiodine therapy is known as the most effective treatment of differentiated thyroid carcinoma (DTC) to ablate remnant thyroid tissue after surgery. In patients with DTC treated with radioiodine, internal radiation dosimetry of radioiodine is useful for radiation risk assessment. The aim of this study is to describe a method to estimate the absorbed dose to the blood using medical internal radiation dosimetry methods. In this study, 23 patients with DTC with different administrated activities, 3.7, 4.62, and 5.55 GBq after thyroidectomy, were randomly selected. Blood dosimetry of treated patients was performed with external whole body counting using a dual-head gamma camera imaging device and also with blood sample activity measurements using a dose calibrator. Absorbed dose to the blood was measured at 2, 6, 12, 24, 48, and 96 hours after the administration of radioiodine with the 2 methods. Based on the results of whole body counting and blood sample activity dose rate measurements, 96 hours after administration of 3.7, 4.62, and 5.55 GBq of radioiodine, absorbed doses to patients' blood were 0.65 ± 0.20, 0.67 ± 0.18, 0.79 ± 0.51 Gy, respectively. Increasing radioiodine activity from 3.7 to 5.55 GBq increased blood dose significantly, while there was no significant difference in blood dose between radioiodine dosages of 3.7 and 4.62 GBq. Our results revealed a significant correlation between the blood absorbed dose and blood sample activity and between the blood absorbed dose and whole body counts 24 to 48 hours after the administration of radioiodine.

Effects of antithyroid drugs on radioiodine treatment: systematic review and meta-analysis of randomised controlled trials

PubMed Central

Briel, Matthias; Christ-Crain, Mirjam; Bonnema, Steen J; Connell, John; Cooper, David S; Bucher, Heiner C; Müller-Brand, Jan; Müller, Beat

2007-01-01

Objective To determine the effect of adjunctive antithyroid drugs on the risk of treatment failure, hypothyroidism, and adverse events after radioiodine treatment. Design Meta-analysis. Data sources Electronic databases (Cochrane central register of controlled trials, Medline, Embase) searched to August 2006 and contact with experts. Review methods Three reviewers independently assessed trial eligibility and quality. Pooled relative risks for treatment failure and hypothyroidism after radioiodine treatment with and without adjunctive antithyroid drugs were calculated with a random effects model. Results We identified 14 relevant randomised controlled trials with a total of 1306 participants. Adjunctive antithyroid medication was associated with an increased risk of treatment failure (relative risk 1.28, 95% confidence interval 1.07 to 1.52; P=0.006) and a reduced risk for hypothyroidism (0.68, 0.53 to 0.87; P=0.006) after radioiodine treatment. We found no difference in summary estimates for the different antithyroid drugs or for whether antithyroid drugs were given before or after radioiodine treatment. Conclusions Antithyroid drugs potentially increase rates of failure and reduce rates of hypothyroidism if they are given in the week before or after radioiodine treatment, respectively. PMID:17309884

A prospective study of the effects of radioiodine therapy for hyperthyroidism in patients with minimally active graves' ophthalmopathy.

PubMed

Perros, Petros; Kendall-Taylor, Pat; Neoh, Chris; Frewin, Sarah; Dickinson, Jane

2005-09-01

Radioiodine is an effective and safe treatment for hyperthyroidism but has been implicated as a risk factor for deterioration or new presentation of Graves' ophthalmopathy (GO). Prophylactic glucocorticoids appear to prevent this effect. The objective of this study was to document the course of GO after radioiodine therapy. This was a prospective observational study. Patients were assessed at baseline and 2, 4, 6, and 12 months after radioiodine therapy. The study was conducted at a tertiary referral center. Seventy-two GO patients with minimally active eye disease participated in the study. A fixed dose of radioiodine was administered. T(4) was commenced 2 wk later to prevent hypothyroidism. Change in activity and severity of GO were analyzed. Exophthalmometer readings, the width of the palpebral aperture, diplopia scores, and the clinical activity score improved significantly. By clinically significant criteria, the eye disease improved in four patients (transiently in three of the four cases), most likely attributable to the natural course of the disease. No patient's eyes deteriorated. Radioiodine is not associated with deterioration of GO in patients with minimally active eye disease when postradioiodine hypothyroidism is prevented.

Personalized Medicine Based on Theranostic Radioiodine Molecular Imaging for Differentiated Thyroid Cancer.

PubMed

Ahn, Byeong-Cheol

2016-01-01

Molecular imaging based personalized therapy has been a fascinating concept for individualized therapeutic strategy, which is able to attain the highest efficacy and reduce adverse effects in certain patients. Theranostics, which integrates diagnostic testing to detect molecular targets for particular therapeutic modalities, is one of the key technologies that contribute to the success of personalized medicine. Although the term "theranostics" was used after the second millennium, its basic principle was applied more than 70 years ago in the field of thyroidology with radioiodine molecular imaging. Differentiated thyroid cancer, which arises from follicular cells in the thyroid, is the most common endocrine malignancy, and theranostic radioiodine has been successfully applied to diagnose and treat differentiated thyroid cancer, the applications of which were included in the guidelines published by various thyroid or nuclear medicine societies. Through better pathophysiologic understanding of thyroid cancer and advancements in nuclear technologies, theranostic radioiodine contributes more to modern tailored personalized management by providing high therapeutic effect and by avoiding significant adverse effects in differentiated thyroid cancer. This review details the inception of theranostic radioiodine and recent radioiodine applications for differentiated thyroid cancer management as a prototype of personalized medicine based on molecular imaging.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahren, B.

The thyroid gland is known to harbor cholinergic and VIPergic nerves. In the present study, the influences of cholinergic stimulation by carbachol, cholinergic blockade by methylatropine and stimulation with various VIP sequences on basal, TSH-induced and VIP-induced thyroid hormone secretion were investigated in vivo in mice. The mice were pretreated with /sup 125/I and thyroxine; the subsequent release of /sup 125/I is an estimation of thyroid hormone secretion. It was found that basal radioiodine secretion was inhibited by both carbachol and methylatropine. Furthermore, TSH-induced radioiodine secretion was inhibited already by a low dose of carbachol. Moreover, a high dose ofmore » carbachol could inhibit VIP-induced radioiodine secretion. Methylatropine did not influence TSH- or VIP-stimulated radioiodine secretion, but counteracted the inhibitory action of carbachol on TSH- and VIP-induced radioiodine release. In addition, contrary to VIP, six various synthesized VIP fragments had no effect on basal or stimulated radioiodine release. It is concluded that basal thyroid hormone secretion is inhibited by both cholinergic activation and blockade. Furthermore, TSH-induced thyroid hormone secretion is more sensitive to inhibition with cholinergic stimulation than is VIP-induced thyroid hormone secretion. In addition, the VIP stimulation of thyroid hormone secretion seems to require the full VIP sequence.« less

Effect of a Low Iodine Diet vs. Restricted Iodine Diet on Postsurgical Preparation for Radioiodine Ablation Therapy in Thyroid Carcinoma Patients.

PubMed

Lim, Chi Young; Kim, Jung-Yeon; Yoon, Mi-Jin; Chang, Hang Seok; Park, Cheong Soo; Chung, Woong Youn

2015-07-01

The radioiodine ablation therapy is required for patients who underwent a total thyroidectomy. Through a comparative review of a low iodine diet (LID) and a restricted iodine diet (RID), the study aims to suggest guidelines that are suitable for the conditions of Korea. The study was conducted with 101 patients. With 24-hour urine samples from the patients after a 2-week restricted diet and after a 4-week restricted diet, the amount of iodine in the urine was estimated. The consumed radioiodine amounts for 2 hours and 24 hours were calculated. This study was conducted with 47 LID patients and 54 RID patients. The amounts of iodine in urine, the 2-week case and 4-week case for each group showed no significant differences. The amounts of iodine in urine between the two groups were both included in the range of the criteria for radioiodine ablation therapy. Also, 2 hours and 24 hours radioiodine consumption measured after 4-week restrictive diet did not show statistical differences between two groups. A 2-week RID can be considered as a type of radioiodine ablation therapy after patients undergo a total thyroidectomy.

Radioiodine in the Savannah River Site environment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kantelo, M.V.; Bauer, L.R.; Marter, W.L.

1993-01-15

Radioiodine, which is the collective term for all radioactive isotopes of the element iodine, is formed at the Savannah River Site (SRS) principally as a by-product of nuclear reactor operations. Part of the radioiodine is released to the environment during reactor and reprocessing operations at the site. The purpose of this report is to provide an introduction to radioiodine production and disposition, its status in the environment, and the radiation dose and health risks as a consequence of its release to the environment around the Savannah River Plant. A rigorous dose reconstruction study is to be completed by thee Centermore » for Disease Control during the 1990s.« less

Protein Binding and Astringent Taste of a Polymeric Procyanidin, 1,2,3,4,6-Penta-O-galloyl-β-D-glucopyranose, Castalagin and Grandinin

PubMed Central

Hofmann, Thomas; Glabasnia, Arne; Schwarz, Bernd; Wisman, Kimberly N.; Gangwer, Kelly A.; Hagerman, Ann E.

2008-01-01

The objective of the present investigation was to examine oral astringency and protein binding activity of four structurally well-defined tannins, namely procyanidin (epicatechin16(4→8)catechin), pentagalloyl glucose (1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose), castalagin, and grandinin, representing the three main structural categories of tannins, the proanthocyanidins, the gallotannins, and the ellagitannins. Astringency threshold and dose response were determined by the half-tongue test using a trained human panel. Protein binding stoichiometry and relative affinity were determined using radioiodinated bovine serum albumin in precipitation or competitive binding assays. Procyanidin and pentagalloyl glucose were perceived as highly astringent compounds and had relatively steep dose response curves but castalagin and grandinin had a lower mass threshold for detection. In vitro, procyanidin was the most effective protein precipitating agent, and grandinin the least. Increasing the temperature increased protein precipitation by the hydrolysable tannins, especially grandinin. All four polyphenols had higher relative affinity for proline-rich proteins than for bovine serum albumin. PMID:17147439

Effect of a Low Iodine Diet vs. Restricted Iodine Diet on Postsurgical Preparation for Radioiodine Ablation Therapy in Thyroid Carcinoma Patients

PubMed Central

Lim, Chi Young; Kim, Jung-Yeon; Yoon, Mi-Jin; Chang, Hang Seok; Park, Cheong Soo

2015-01-01

Purpose The radioiodine ablation therapy is required for patients who underwent a total thyroidectomy. Through a comparative review of a low iodine diet (LID) and a restricted iodine diet (RID), the study aims to suggest guidelines that are suitable for the conditions of Korea. Materials and Methods The study was conducted with 101 patients. With 24-hour urine samples from the patients after a 2-week restricted diet and after a 4-week restricted diet, the amount of iodine in the urine was estimated. The consumed radioiodine amounts for 2 hours and 24 hours were calculated. Results This study was conducted with 47 LID patients and 54 RID patients. The amounts of iodine in urine, the 2-week case and 4-week case for each group showed no significant differences. The amounts of iodine in urine between the two groups were both included in the range of the criteria for radioiodine ablation therapy. Also, 2 hours and 24 hours radioiodine consumption measured after 4-week restrictive diet did not show statistical differences between two groups. Conclusion A 2-week RID can be considered as a type of radioiodine ablation therapy after patients undergo a total thyroidectomy. PMID:26069126

Radioiodination of chicken luteinizing hormone without affecting receptor binding potency

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kikuchi, M.; Ishii, S.

1989-12-01

By improving the currently used lactoperoxidase method, we were able to obtain radioiodinated chicken luteinizing hormone (LH) that shows high specific binding and low nonspecific binding to a crude plasma membrane fraction of testicular cells of the domestic fowl and the Japanese quail, and to the ovarian granulosa cells of the Japanese quail. The change we made from the original method consisted of (1) using chicken LH for radioiodination that was not only highly purified but also retained a high receptor binding potency; (2) controlling the level of incorporation of radioiodine into chicken LH molecules by employing a short reactionmore » time and low temperature; and (3) fractionating radioiodinated chicken LH further by gel filtration using high-performance liquid chromatography. Specific radioactivity of the final {sup 125}I-labeled chicken LH preparation was 14 microCi/micrograms. When specific binding was 12-16%, nonspecific binding was as low as 2-4% in the gonadal receptors. {sup 125}I-Labeled chicken LH was displaced by chicken LH and ovine LH but not by chicken follicle-stimulating hormone. The equilibrium association constant of quail testicular receptor was 3.6 x 10(9) M-1. We concluded that chicken LH radioiodinated by the present method is useful for studies of avian LH receptors.« less

Gastrointestinal Side Effects of the Radioiodine Therapy for the Patients with Differentiated Thyroid Carcinoma Two Days after Prescription.

PubMed

Pashnehsaz, Mehran; Takavar, Abbas; Izadyar, Sina; Zakariaee, Seyed Salman; Mahmoudi, Mahmoud; Paydar, Reza; Geramifar, Parham

2016-09-01

Iodine-131 (I-131) therapy is one of the conventional approaches in the treatment of patients with differentiated thyroid carcinoma (DTC). The radioiodine agents also accumulate in the other organs that cause pain and damage to the patients. Radioiodine therapy is associated with various gastrointestinal (GI) toxicities. In this study, GI side effects of the radioiodine therapy were investigated. GI toxicities of the radioiodine therapy were studied in 137 patients with histologically proven DTC in Jun-Nov 2014. All the patients were treated by radioiodine agents in the research institute of Shariati Hospital, Tehran, Iran. The patients were examined 48 h after prescription (before discharge) and their GI side effects were registered. Correlation of the age, gender, administered dose, administered dose per body weight as the independent factors, and GI side effects were analyzed using the Pearson correlation test with Statistical Package for the Social Sciences (SPSS) version 20. Regression coefficients and linearity of the variable were investigated by MATLAB software. Line fitting was performed using MATLAB curve-fitting toolbox. From the subjects, 38 patients had GI complaints (30.4%). Significant factors influencing GI side effects were dose per body weight and administered doses. There was no significant correlation between age and gender as the independent parameters and GI complaints. The most prevalent GI side effect was nausea that occurs in 26.4% of the patients. From the results, it could be concluded that the GI side effects could be prevented by administering a safe radioiodine dose value less than 5,550 MBq.

[Radioiodine 131I therapy of hyperthyroidism on an outpatient basis - safe, effective and economic option].

PubMed

Jiskra, J; Kubinyi, J; Telička, Z

2012-02-01

Radioiodine 131I therapy of hyperthyroidism on an outpatient basis is widely accepted over the world. In Czech Republic, however, radioiodine therapy is still not enough used, and has been realized on an inpatient basis to date. Our work is the first analysis of the experiences with radioiodine therapy of hyperthyroidism on an outpatient basis in Czech Republic. Capsule with 550 MBq of 131I was administered orally in 39 hyperthyroid patients (32 women and 8 men, 21 with autoimmune Graves hyperthyroidism and 18 with toxic thyroid nodules, mean age 66.8 years). In 32 of them we evaluated effectiveness and complications of therapy after 12-42 months. We also compared financial costs of the radioiodine treatment on an outpatient basis with the treatment in hospitalization and with surgery. After the treatment, 9/32 (28 %) patients were euthyroid without thyrostatic/thyroxine treatment, 18/32 (60 %) patients were hypothyroid with thyroxine therapy, 2/32 (6 %) patients significantly decreased doses of thyrostatic drugs. In 2/32 (6 %) patients the treatment was ineffective. The effect of the treatment did not depend on the etiology and severity of hyperthyroidism, but decreased with thyroid volume. Patients with ineffective or only partially effective treatment had median of thyroid volume more than 40 ml. In 1 patient thyroid associated ophthalmopathy was moderately worsened. Other complications were not observed. If we compared financial costs in model with 1 patient, we found that the costs of radioiodine therapy on an outpatient basis (118.7 €) comprise only 16 % of the costs of radioiodine therapy in hospitalization (728 €) and only 25 % of the costs of surgery (475.6 €). Radioiodine 131I is effective and safe in the treatment of hyperthyroidism and the therapy on an outpatient basis is much cheaper choice. The therapy with 131I on an outpatient basis is not suitable in patients with thyroid volume more than 40 ml.

Development of Tethered Hsp90 Inhibitors Carrying Radioiodinated Probes to Specifically Discriminate and Kill Malignant Breast Tumor Cells

DTIC Science & Technology

2016-05-01

AWARD NUMBER: W81XWH-15-1-0072 TITLE: Development of Tethered Hsp90 Inhibitors Carrying Radioiodinated Probes to Specifically Discriminate and...1 May 2015 - 30 Apr 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Development of Tethered Hsp90 Inhibitors Carrying Radioiodinated Probes to...inhibitor capable of carrying various radioactive iodine isotopes for early detection and ablation of metastatic breast cancers. These probes

Effects of drugs on the efficacy of radioiodine (|) therapy in hyperthyroid patients.

PubMed

Oszukowska, Lidia; Knapska-Kucharska, Małgorzata; Lewiński, Andrzej

2010-03-01

The treatment of hyperthyroidism is targeted at reducing the production of thyroid hormones by inhibiting their synthesis or suppressing their release, as well as by controlling their influence on peripheral tissue (conservative therapy, medical treatment). Radical treatment includes surgical intervention to reduce the volume of thyroid tissue or damage of the mechanisms of thyroid hormone synthesis by radioiodine ((131)|) administration. Radioiodine ((131)|) is a reactor radionuclide, produced as a result of uranium decomposition and emission of β and γ radiation. The therapeutic effects of the isotope are obtained by the emission of β radiation. In the paper, the effects of administered drugs (antithyroid, glucocorticosteroids, lithium carbonate, inorganic iodine, β-blockers) on the final outcome of radioiodine therapy in patients with hyperthyroidism are discussed.

Improved iodine radiolabels for monoclonal antibody therapy.

PubMed

Stein, Rhona; Govindan, Serengulam V; Mattes, M Jules; Chen, Susan; Reed, Linda; Newsome, Guy; McBride, Bill J; Griffiths, Gary L; Hansen, Hans J; Goldenberg, David M

2003-01-01

A major disadvantage of (131)iodine (I)-labeled monoclonal antibodies (MAbs) for radioimmunotherapy has been the rapid diffusion of iodotyrosine from target cells after internalization and catabolism of the radioiodinated MAbs. We recently reported that a radioiodinated, diethylenetriaminepentaacetic acid-appended peptide, designated immunomedics' residualizing peptide 1 (IMP-R1), was a residualizing iodine label that overcame many of the limitations that had impeded the development of residualizing iodine for clinical use. To determine the factors governing the therapeutic index of the labeled MAb, as well as the factors required for production of radioiodinated MAb in high yield and with high specific activity, variations in the peptide structure of IMP-R1 were evaluated. A series of radioiodinated, diethylenetriaminepentaacetic acid-appended peptide moieties (IMP-R1 through IMP-R8) that differed in overall hydrophilicity and charge were compared. Radioiodinations of the peptides followed by conjugations to disulfide-reduced RS7 (an anti-epithelial glycoprotein-1 MAb) furnished radioimmunoconjugates in good overall incorporations, with immunoreactivities comparable to that of directly radioiodinated RS7. Specific activities of up to 8 mCi/mg and yields > 80% have been achieved. In vitro processing experiments showed marked increases in radioiodine retention with all of the adducts; radioiodine retention at 45 h was up to 86% greater in cells than with directly iodinated RS7. Each of the (125)I-peptide-RS7 conjugates was compared with (131)I-RS7 (labeled by the chloramine-T method) in paired-label biodistribution studies in nude mice bearing human lung tumor xenografts. All of the residualizing substrates exhibited significantly enhanced retention in tumor in comparison to directly radioiodinated RS7, but the nontarget uptakes differed significantly among the residualizing labels. The best labels were IMP-R4 and IMP-R8, showing superior tumor-to-non-tumor ratios by virtue of high tumor uptake and retention and low normal organ uptake, as well as superior radiochemical properties. The therapeutic efficacy of (131)I-IMP-R4-RS7 was compared with that of conventionally (131)I-labeled RS7 and (90)yttrium-RS7 in the nude mice lung cancer model. The therapeutic efficacy of (131)I-IMP-R4-RS7 and (90)yttrium-RS7 were equivalent, and both agents yielded significantly improved control of tumor growth compared with conventional (131)I-labeled RS7.

Peptide receptor radionuclide therapy of treatment-refractory metastatic thyroid cancer using 90Yttrium and 177Lutetium labeled somatostatin analogs: toxicity, response and survival analysis

PubMed Central

Budiawan, Hendra; Salavati, Ali; Kulkarni, Harshad R; Baum, Richard P

2014-01-01

The overall survival rate of non-radioiodine avid differentiated (follicular, papillary, medullary) thyroid carcinoma is significantly lower than for patients with iodine-avid lesions. The purpose of this study was to evaluate toxicity and efficacy (response and survival) of peptide receptor radionuclide therapy (PRRT) in non-radioiodine-avid or radioiodine therapy refractory thyroid cancer patients. Sixteen non-radioiodine-avid and/or radioiodine therapy refractory thyroid cancer patients, including follicular thyroid carcinoma (n = 4), medullary thyroid carcinoma (n = 8), Hürthle cell thyroid carcinoma (n = 3), and mixed carcinoma (n = 1) were treated with PRRT by using 90Yttrium and/or 177Lutetium labeled somatostatin analogs. 68Ga somatostatin receptor PET/CT was used to determine the somatostatin receptor density in the residual tumor/metastatic lesions and to assess the treatment response. Hematological profiles and renal function were periodically examined after treatment. By using fractionated regimen, only mild, reversible hematological toxicity (grade 1) or nephrotoxicity (grade 1) were seen. Response assessment (using EORTC criteria) was performed in 11 patients treated with 2 or more (maximum 5) cycles of PRRT and showed disease stabilization in 4 (36.4%) patients. Two patients (18.2%) showed partial remission, in the remaining 5 patients (45.5%) disease remained progressive. Kaplan-Meier analysis resulted in a mean survival after the first PRRT of 4.2 years (95% CI, range 2.9-5.5) and median progression free survival of 25 months (inter-quartiles: 12-43). In non-radioiodine-avid/radioiodine therapy refractory thyroid cancer patients, PRRT is a promising therapeutic option with minimal toxicity, good response rate and excellent survival benefits. PMID:24380044

Effects of hemodialysis on iodine-131 biokinetics in thyroid carcinoma patients with end-stage chronic renal failure.

PubMed

Yeyin, Nami; Cavdar, Iffet; Uslu, Lebriz; Abuqbeitah, Mohammad; Demir, Mustafa

2016-03-01

Radioiodine therapy could be challenging in chronic renal failure patients requiring hemodialysis. The aim of this study was to establish the effects of hemodialysis on elimination of radioiodine from the body in thyroid carcinoma patients with end-stage chronic renal failure and to determine its effects on environmental radiation dose. Three end-stage chronic renal failure patients (four cases) diagnosed with differentiated thyroid carcinoma requiring radioiodine therapy were included in our study. Each patient was given 50-75 mCi (1850-2775 MBq) iodine-131 with 50% dose reduction. Dose rate measurement was performed at the 2nd, 24th, and 48th hour (immediately before and after hemodialysis) after radioiodine administration. The Geiger-Müller probe was held at 1 m distance at the level of the midpoint of the thorax for the dose rate measurement. The effective half-life of iodine-131 for three patients was found to be 44 h. In conclusion, the amount of radioiodine excreted per hemodialysis session was calculated to be 51.25%.

Thyroid Carcinoma

PubMed

Ahmed, Najeeb; Niyaz, Kashif; Borakati, Aditya; Marafi, Fahad; Birk, Rubinder; Usmani, Sharjeel

2018-02-26

Differentiated thyroid cancer (DTC) has a good prognosis overall; however, lifelong follow-up is required for many cases. Radioiodine planar imaging with iodine-123 (I-123) or radioiodine-131 (I-131) remains the standard in the follow-up after initial surgery and ablation of residual thyroid tissue using I-131 therapy. Radioiodine imaging is also used in risk-stratifying and for staging of thyroid cancer, and in long-term follow-up. Unfortunately, the lack of anatomical detail on planar gamma camera imaging and superimposition of areas presenting with increased radioiodine uptake can make accurate diagnosis and localization of radioiodine-avid metastatic disease challenging, leading to false positive results and potentially to over-treatment of patients. Hybrid SPECT/CT allows precise anatomical localization and superior characterization of foci of increased tracer uptake when compared to planar imaging. This, in turn, allows the differentiation of pathological and physiological uptake, increasing the accuracy of image interpretation and ultimately improving the accuracy of DTC staging and subsequent patient management. In this review, we look at the unique and emerging role that SPECT/CT plays in the management of DTC, illustrated by examples from our own clinical practice. Creative Commons Attribution License

Influence of convection on the diffusive transport and sieving of water and small solutes across the peritoneal membrane.

PubMed

Asghar, Ramzana B; Diskin, Ann M; Spanel, Patrik; Smith, David; Davies, Simon J

2005-02-01

The three-pore model of peritoneal membrane physiology predicts sieving of small solutes as a result of the presence of a water-exclusive pathway. The purpose of this study was to measure the diffusive and convective components of small solute transport, including water, under differing convection. Triplicate studies were performed in eight stable individuals using 2-L exchanges of bicarbonate buffered 1.36 or 3.86% glucose and icodextrin. Diffusion of water was estimated by establishing an artificial gradient of deuterated water (HDO) between blood/body water and the dialysate. (125)RISA (radio-iodinated serum albumin) was used as an intraperitoneal volume marker to determine the net ultrafiltration and reabsorption of fluid. The mass transfer area coefficient (MTAC) for HDO and solutes was estimated using the Garred and Waniewski equations. The MTAC of HDO calculated for 1.36% glucose and icodextrin were similar (36.8 versus 39.7 ml/min; P = 0.3), whereas for other solutes, values obtained using icodextrin were consistently higher (P < 0.05). A significant increase in the MTAC of HDO was demonstrated with an increase in the convective flow of water when using 3.86% glucose (mean value, 49.5 ml/min; P < 0.05). MTAC for urea was also increased with 3.86% glucose. The identical MTAC for water using 1.36% glucose and icodextrin indicates that diffusion is predominantly through small pores, whereas the difference in MTAC for the remaining solutes is a reflection of their sieving. The increase in the MTAC of water and urea associated with an increase in convection is most likely due to increased mixing within the interstitium.

Efficiency analysis of using tailored individual doses of radioiodine and fine tuning using a low-dose antithyroid drug in the treatment of Graves' disease.

PubMed

Liu, Chang-Jiang; Dong, Yan-Yu; Wang, Yi-Wei; Wang, Kai-Hua; Zeng, Qun-Yan

2011-03-01

To evaluate the effect of using tailored individual doses of radioiodine (¹³¹I) and fine tuning using low-dose antithyroid drug (ATD) in the treatment of Graves' disease, and an attempt to establish a therapeutic strategy that can keep both high rate of euthyroidism and low incidence of hypothyroidism. The dose of radioiodine was calculated using the calculated dose formula, and low-dose ATD was used as a way of fine tuning during follow-up. The intended dose of radioiodine was modified according to the patient's age at radioiodine therapy, thyroid size, and duration of hyperthyroidism before radioiodine therapy in the study group; it was set as 2.96 MBq/g of thyroid in the control group. Twenty patients with Graves' disease were nonrandomly assigned to the control group and 98 patients with Graves' disease to the study group. The outcomes, which included euthyroidism, hypothyroidism, and persistent hyperthyroidism, were determined according to the patients' states at the end of follow-up. In the study group, 74 patients (75.5%) achieved the euthyroid state, six patients (6.1%) became hypothyroid, and 18 patients (18.4%) remained hyperthyroid. The rate of euthyroidism was statistically different between the study group and the control group (75.5 vs. 50%, P=0.03). Of 98 patients with Graves' disease in the study group, 19 patients were additionally treated with ATD during follow-up, and 12 patients achieved euthyroidism. In different age groups or duration of hyperthyroidism groups, the rate of euthyroidism was not statistically different among subgroups of goiter grade 1, grade 2, and grade 3 (P>0.05). Similarly, in different age groups or duration of hyperthyroidism groups, the incidence of hypothyroidism was not statistically different among subgroups of goiter grade 1, grade 2, and grade 3 (P>0.05). However, binary logistic regression analysis showed that thyroid size was associated with overtreatment and undertreatment in our study. Individual doses of radioiodine, adjusted according to the patient's age, thyroid size, and duration of hyperthyroidism, combined with low-dose ATD for some patients, 1 month or more after radioiodine therapy, was an effective method for treating Graves' disease. Our data showed that using tailored individual doses of radioiodine and fine tuning using low-dose ATD may well be a way to keep both high rate of euthyroidism and low incidence of hypothyroidism. The dose of radioiodine should be decreased a little for small goiter and increased a little for large goiter on the basis of our treatment protocol in future study.

Orbital flourine-18-fluorodeoxyglucose positron emission tomography in patients with Graves' disease for evaluation of active inflammation.

PubMed

Uslu-Beşli, Lebriz; Kabasakal, Levent; Sağer, Sait; Cicik, Erdoğan; Asa, Sertaç; Sönmezoğlu, Kerim

2017-11-01

Prediction and early diagnosis of orbitopathy is needed in patients with Graves' disease, especially when radioiodine therapy is planned. Positron emission tomography/computerized tomography (PET/CT) using flourine-18-fluorodeoxyglucose (FDG) is an effective imaging modality in detection of inflammation, however, its ability to detect orbital inflammation has not been well studied. The aim of our study is to determine the ability of FDG PET/CT to detect orbital inflammation related with Graves' disease, identify active orbitopathy, predict the radioiodine-triggered orbitopathy, and find out the effects of radioiodine on orbital inflammation. Total 31 Graves' disease patients and 17 controls were included. All Graves' disease patients underwent cranial FDG PET/CT imaging prior therapy. Radioiodine therapy and post-treatment PET/CT study was applied to 21 patients. PET/CT images of all examinees were evaluated, measuring extraocular muscle maximum standard uptake value (SUVmax) and muscle thickness. FDG uptake was increased in the majority of extraocular muscles in Graves' disease patients in comparison to controls and this increase was found to be irrelevant from muscle thickness. Extraocular muscle SUVmax values did not increase in Graves' orbitopathy patients who received radioiodine under corticosteroid prophylaxis. SUVmax level of all orbital rectus muscles were increased after radioiodine therapy in nonsmokers, whereas no increase was detected in smokers. FDG PET/CT may be helpful in detection of extraocular muscle inflammation and it may show ongoing orbitopathy in early stages of inflammation before anatomical changes occur.

Persistent high TRAb values during pregnancy predict increased risk of neonatal hyperthyroidism following radioiodine therapy for refractory hyperthyroidism.

PubMed

Hamada, Noboru; Momotani, Naoko; Ishikawa, Naofumi; Yoshimura Noh, Jaeduk; Okamoto, Yasuyuki; Konishi, Toshiaki; Ito, Koichi; Ito, Kunihiko

2011-01-01

Serum levels of TSH receptor antibody (TRAb) often increase after radioiodine treatment for Graves' disease, and high-serum levels of maternal TRAb in late pregnancy indicate a risk of neonatal hyperthyroidism. The aim of this retrospective study is to investigate the characteristics of Graves' women who had a history of radioiodine treatment for intractable Graves' disease, and whose neonates suffered from hyperthyroidism. The subjects of this study were 45 patients with Graves' disease who became pregnant during the period from 1988 to 1998 after receiving radioiodine treatment at Ito Hospital. 25 of the 45 subjects had had a relapse of hyperthyroidism after surgical treatment for Graves' disease. 19 pregnancies were excluded because of artificial or spontaneous abortion. In the remaining 44 pregnancies of 35 patients, neonatal hyperthyroidism developed in 5 (11.3%) pregnancies of 4 patients. Serum levels of TRAb at delivery were higher in patients whose neonates suffered from hyperthyroidism (NH mother) than those of patients who delivered normal infants (N mother). Furthermore, serum levels of TRAb in NH mother did not change during pregnancy, although those of 4 patients of N mother, in which serum levels of TRAb before radioiodine treatment were as high as in NH mother, decreased significantly during pregnancy. In conclusion, women who delivered neonates with hyperthyroidism following radioiodine treatment seem to have very severe and intractable Graves' disease. Persistent high TRAb values during pregnancy observed in those patients may be a cause of neonatal hyperthyroidism.

Risk factors for persistent atrial fibrillation following successful hyperthyroidism treatment with radioiodine therapy.

PubMed

Zhou, Zhen-Hu; Ma, Long-Le; Wang, Le-Xin

2011-01-01

To investigate the predicting factors for persistent atrial fibrillation (AF) following radioiodine therapy for hyperthyroidism. Standard 12-lead ECG and 24-h Holter monitoring were performed in 94 patients (38 males, mean age 46.1±8.2 years) with persistent AF following radioiodine therapy for hyperthyroidism. Left ventricular (LV) function was assessed with two-dimensional echocardiography. Euthyroidism or hypothyroidism was achieved in 81% and 19% of the patients, respectively, after radioiodine therapy. At the end of follow-up (1.6±1.3 years), LV ejection fraction in the 52 patients with LV dysfunction was increased from 39.3±3.3% to 59.0±5.5% (p<0.01). In the 38 patients with pre-treatment paroxysmal AF, no AF was documented during the follow-up. In the 45 patients with pre-treatment persistent AF, AF was found in 27 (60%) during the follow-up. Multivariate logistic regression analysis showed that more than 55 years old in age (RR 2.76, 95% CI: 1.16-8.79, p<0.01), duration of hyperthyroidism (RR 3.08, 95% CI: 1.22-11.41, p<0.01) and duration of pre-treatment atrial fibrillation (RR 2.96, 95% CI: 1.31-7.68, p<0.01) were independent predictors for persistent AF following radioiodine therapy. Older age, duration of hyperthyroidism and pre-treatment duration of AF are risk factors for persistent AF following radioiodine therapy.

Brain-derived neurotrophic factor inhibits glucose intolerance after cerebral ischemia

PubMed Central

Shu, Xiaoliang; Zhang, Yongsheng; Xu, Han; Kang, Kai; Cai, Donglian

2013-01-01

Brain-derived neurotrophic factor is associated with the insulin signaling pathway and glucose tabolism. We hypothesized that expression of brain-derived neurotrophic factor and its receptor may be involved in glucose intolerance following ischemic stress. To verify this hypothesis, this study aimed to observe the changes in brain-derived neurotrophic factor and tyrosine kinase B receptor expression in glucose metabolism-associated regions following cerebral ischemic stress in mice. At day 1 after middle cerebral artery occlusion, the expression levels of brain-derived neurotrophic factor were significantly decreased in the ischemic cortex, hypothalamus, liver, skeletal muscle, and pancreas. The expression levels of tyrosine kinase B receptor were decreased in the hypothalamus and liver, and increased in the skeletal muscle and pancreas, but remained unchanged in the cortex. Intrahypothalamic administration of brain-derived neurotrophic factor (40 ng) suppressed the decrease in insulin receptor and tyrosine-phosphorylated insulin receptor expression in the liver and skeletal muscle, and inhibited the overexpression of gluconeogenesis-associated phosphoenolpyruvate carboxykinase and glucose-6-phosphatase in the liver of cerebral ischemic mice. However, serum insulin levels remained unchanged. Our experimental findings indicate that brain-derived neurotrophic factor can promote glucose metabolism, reduce gluconeogenesis, and decrease blood glucose levels after cerebral ischemic stress. The low expression of brain-derived neurotrophic factor following cerebral ischemia may be involved in the development of glucose intolerance. PMID:25206547

Radioiodine Accumulation in a Giant Ovarian Cystadenofibroma Detected Incidentally by 131-I Whole Body Scans

PubMed Central

Mebarki, Mohammed; Menemani, Abdelghani; Medjahedi, Abdelkader; Boualou, Fouad; Slama, Abdelhak; Ouguirti, Sarah; Kherbouche, Fatima Zahra; Berber, Nécib

2012-01-01

Ovarian cystadenofibroma is a relatively rare tumor; it is usually asymptomatic and is found incidentally. We present the case of a 24-year-old female patient, who had undergone total thyroidectomy for thyroid papillary carcinoma, with an asymptomatic giant cystadenofibroma, incidentally discovered by diagnostic 131I-SPECT/CT WBSs. We summarize the clinical history, imaging data, and histopathological study on a rare case of radioiodine accumulation in cystadenofibroma, and we discuss the mechanism of uptake of radioiodine in this case. PMID:23119215

Radioiodine therapy for thyroid cancer depicted uterine leiomyoma.

PubMed

Hirata, Kenji; Shiga, Tohru; Kubota, Kanako C; Okamoto, Shozo; Kamibayashi, Tomohito; Tamaki, Nagara

2009-03-01

A 55-year-old woman underwent radioiodine therapy for papillary carcinoma of the thyroid. Post-therapeutic I-131 scan revealed radioiodine uptake in the pelvic region and in the thyroid bed. CT revealed a huge mass connected to the uterus. The tumor was operated on and histologically proven to be a leiomyoma of the uterus. Some physiological conditions or nonthyroidal diseases can cause false positives in patients with postoperative thyroid cancer. We suggest that uterine leiomyoma might be added to the pitfall list, although the mechanism of I-131 uptake remains unclear.

SPECT/CT localization of oral radioiodine activity: a retrospective study and in-vitro assessment.

PubMed

Burlison, Jared S; Hartshorne, Michael F; Voda, Alan M; Cocks, Franklin H; Fair, Joanna R

2013-12-01

We sought to further localize radioiodine activity in the mouth on post-thyroid cancer therapy imaging using single-photon emission computed tomography/computed tomography (SPECT/CT). We retrospectively reviewed all patients (58) who underwent thyroid cancer therapy with iodine-131 (131I) at our institution from August 2009 to March 2011 whose post-therapy radioiodine imaging included neck SPECT/CT. A small group (six) of diagnostic 131I scans including SPECT/CT was also reviewed. Separately, we performed in-vitro 131I (sodium iodide) binding assays with amalgam and Argenco HP 77 (77% dental gold alloy) as proof of principle for these interactions. Of the 58 post-therapy patients, 45 (78%) had undergone metallic dental restorations, and of them 41 (91%) demonstrated oral 131I activity localizing preferentially to those restorations. It was observed that radioiodine also localized to other dental restorations and to orthodontic hardware. Gum-line activity in edentulous patients suggests radioiodine interaction with denture adhesive. In vitro, dental amalgam and Argenco HP 77 bound 131I in a time-dependent manner over 1-16 days of exposure. Despite subsequent washings with normal saline, significant 131I activity (maximally 12% for amalgam and 68% for Argenco HP 77) was retained by these metals. Subsequent soaking in a saturated solution of potassium iodide partially displaced 131I from amalgam, with near-total displacement of I from Argenco HP 77. SPECT/CT shows that radioiodine in the oral cavity localizes to metallic dental restorations. Furthermore, in-vitro studies demonstrate partially reversible binding of 131I to common dental metals.

Radioiodine therapy of hyperfunctioning thyroid nodules: usefulness of an implemented dose calculation algorithm allowing reduction of radioiodine amount.

PubMed

Schiavo, M; Bagnara, M C; Pomposelli, E; Altrinetti, V; Calamia, I; Camerieri, L; Giusti, M; Pesce, G; Reitano, C; Bagnasco, M; Caputo, M

2013-09-01

Radioiodine is a common option for treatment of hyperfunctioning thyroid nodules. Due to the expected selective radioiodine uptake by adenoma, relatively high "fixed" activities are often used. Alternatively, the activity is individually calculated upon the prescription of a fixed value of target absorbed dose. We evaluated the use of an algorithm for personalized radioiodine activity calculation, which allows as a rule the administration of lower radioiodine activities. Seventy-five patients with single hyperfunctioning thyroid nodule eligible for 131I treatment were studied. The activities of 131I to be administered were estimated by the method described by Traino et al. and developed for Graves'disease, assuming selective and homogeneous 131I uptake by adenoma. The method takes into account 131I uptake and its effective half-life, target (adenoma) volume and its expected volume reduction during treatment. A comparison with the activities calculated by other dosimetric protocols, and the "fixed" activity method was performed. 131I uptake was measured by external counting, thyroid nodule volume by ultrasonography, thyroid hormones and TSH by ELISA. Remission of hyperthyroidism was observed in all but one patient; volume reduction of adenoma was closely similar to that assumed by our model. Effective half-life was highly variable in different patients, and critically affected dose calculation. The administered activities were clearly lower with respect to "fixed" activities and other protocols' prescription. The proposed algorithm proved to be effective also for single hyperfunctioning thyroid nodule treatment and allowed a significant reduction of administered 131I activities, without loss of clinical efficacy.

Single photon emission computed tomography imaging for temporal dynamics of thyroidal and salivary radionuclide accumulation in 17-allyamino-17-demothoxygeldanamycin-treated thyroid cancer mouse model

PubMed Central

Liu, Yu-Yu; Brandt, Michael P; Shen, Daniel H; Kloos, Richard T; Zhang, Xiaoli; Jhiang, Sissy M

2014-01-01

Selective iodide uptake and prolonged iodine retention in the thyroid is the basis for targeted radioiodine therapy for thyroid cancer patients; however, salivary gland dysfunction is the most frequent nonthyroidal complications. In this study, we have used noninvasive single photon emission computed tomography functional imaging to quantify the temporal dynamics of thyroidal and salivary radioiodine accumulation in mice. At 60 min post radionuclide injection, radionuclide accumulation in the salivary gland was generally higher than that in thyroid due to much larger volume of the salivary gland. However, radionuclide accumulation per anatomic unit in the salivary gland was lower than that in thyroid and was comparable among mice of different age and gender. Differently, radionuclide accumulation per anatomic unit in thyroid varied greatly among mice. The extent of thyroidal radioiodine accumulation stimulated by a single dose of exogenous bovine TSH (bTSH) in triiodothyronine (T3)-supplemented mice was much less than that in mice received neither bTSH nor T3 (nontreated mice), suggesting that the duration of elevated serum TSH level is important to maximize thyroidal radioiodine accumulation. Furthermore, the extent and duration of radioiodine accumulation stimulated by bTSH was less in the thyroids of the thyroid-targeted RET/PTC1 (thyroglobulin (Tg)-PTC1) mice bearing thyroid tumors compared with the thyroids in wild-type (WT) mice. Finally, the effect of 17-allyamino-17-demothoxygeldanamycin on increasing thyroidal, but not salivary, radioiodine accumulation was validated in both WT mice and Tg-PTC1 preclinical thyroid cancer mouse model. PMID:20943721

a Study of the Interferences with the On-Line Radioiodine Measurement Under Nuclear Accident Conditions

NASA Astrophysics Data System (ADS)

Tseng, Tung-Tse

In this research the interferences with the on -line detection of radioiodines, under nuclear accident conditions, were studied. The special tool employed for this research is the developed on-line radioiodine monitor (the Penn State Radioiodine Monitor), which is capable of detecting low levels of radioiodine on-line in air containing orders of magnitude higher levels of radioactive noble gases. Most of the data reported in this thesis were collected during a series of experiments called "Source -Term Experiment Program (STEP)." The experiments were conducted at the Argonne National Laboratory's TREAT reactor located at the Idaho National Engineering Laboratory (INEL). In these tests, fission products were released from the Light Water Reactor (LWR) test fuels as a result of simulating a reactor accident. The Penn State Monitor was then used to sample the fission products accumulated in a large container which simulated the reactor containment building. The test results proved that the Penn State Monitor was not affected significantly by the passage of large amounts of noble gases through the system. Also, it confirmed the predicted results that the operation of conventional on-line radioiodine detectors would, under nuclear accident conditions, be seriously impaired by the passage of high concentrations of radioactive noble gases through such systems. This work also demonstrated that under conditions of high noble gas concentrations and low radioiodine concentrations, the formation of noble-gas-decayed alkali metals can seriously interfere with the on-line detection of radioiodine, especially during the 24 hours immediately after the accident. The decayed alkali metal particulates were also found to be much more penetrating than the ordinary type of particulates, since a large fraction (15%) of the particulates were found to penetrate through the commonly used High Efficiency Particulate Air (HEPA) filter (rated >99.97% for 0.3 (mu)m particulate). Also, a significant fraction ((TURN)40%) of these particles became deposited on silver zeolite iodine filters inside the counting chamber. Finally, the Penn State Monitor proved itself to be a powerful research tool for the on-line source term studies since it can easily produce near noble-gas-free spectra during the real time studies occurring under simulated nuclear accident conditions.

Influence of N-alkylation on organ distribution of radioiodinated amphetamines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Machulla, H.J.; Schmidt, U.; Mehdorn, H.M.

1985-05-01

In spite of numerous animal data and the widespread clinical application of p-(I-123)-N-isopropyl-amphetamine, questions remain open about the role of N-alkylation. Therefore, amphetamine (AP), N-methyl- (MeAP), and N-isopropyl-amphetamine (IsAP) were radioiodinated in the para position and the organ distribution was determined in male mice (Freiburg tribe) 10 weeks of age. In the lungs, all derivatives showed principally the same kinetics. In brain, the maximum uptake was reached after 30 min with 12%/g for AP and MeAP, and 10.5%/g for IsAP. In liver, the radioactivity similarly increased during the first 15 min to approx. 12%/g; afterwards, AP clearly decreased but MeAPmore » remained almost constant up to 120 min and, even more, IsAP increased to a maximum of 18%/g at 30 min. The same brain uptake kinetics for all 3 substances exclude the importance of lipophilicity increased by the N-alkylation. Furthermore, the differences in the liver kinetics of AP and both MeAP and IsAP indicate the importance of liver metabolism on the alkylated amphetamines. The results support the hypothesis that the first important metabolite of the N-alkylated derivatives is the amphetamine which accumulates in the brain as do MeAP and IsAP. On the basis of these findings, AP was applied clinically showing the same efficient brain uptake and distribution in SPECT as IsAP.« less

Immobilization of radioiodine in synthetic boracite

DOEpatents

Babad, H.; Strachan, D.M.

1982-09-23

A nuclear waste storage product is disclosed in which radioiodine is incorporated in a synthetic boracite. The boracite may be prepared by reacting a transition metal iodide with an alkali horate under mild hydrothermal conditions, drying the reaction product, and then hot pressing.

Comparative study of expression and activity of glucose transporters between stem cell-derived brain microvascular endothelial cells and hCMEC/D3 cells.

PubMed

Al-Ahmad, Abraham J

2017-10-01

Glucose constitutes a major source of energy of mammalian brains. Glucose uptake at the blood-brain barrier (BBB) occurs through a facilitated glucose transport, through glucose transporter 1 (GLUT1), although other isoforms have been described at the BBB. Mutations in GLUT1 are associated with the GLUT1 deficiency syndrome, yet none of the current in vitro models of the human BBB maybe suited for modeling such a disorder. In this study, we investigated the expression of glucose transporters and glucose diffusion across brain microvascular endothelial cells (BMECs) derived from healthy patient-derived induced pluripotent stem cells (iPSCs). We investigated the expression of different glucose transporters at the BBB using immunocytochemistry and flow cytometry and measured glucose uptake and diffusion across BMEC monolayers obtained from two iPSC lines and from hCMEC/D3 cells. BMEC monolayers showed expression of several glucose transporters, in particular GLUT1, GLUT3, and GLUT4. Diffusion of glucose across the monolayers was mediated via a saturable transcellular mechanism and partially inhibited by pharmacological inhibitors. Taken together, our study suggests the presence of several glucose transporters isoforms at the human BBB and demonstrates the feasibility of modeling glucose across the BBB using patient-derived stem cells. Copyright © 2017 the American Physiological Society.

Ecofriendly antiglare film derived from biomass using ultraviolet curing nanoimprint lithography for high-definition display

NASA Astrophysics Data System (ADS)

Takei, Satoshi; Murakami, Gaku; Mori, Yuto; Ichikawa, Takumi; Sekiguchi, Atsushi; Obata, Tsutomu; Yokoyama, Yoshiyuki; Mizuno, Wataru; Sumioka, Junji; Horita, Yuji

2013-07-01

Nanopatterning of an ecofriendly antiglare film derived from biomass using an ultraviolet curing nanoimprint lithography is reported. Developed sugar-related organic compounds with liquid glucose and trehalose derivatives derived from biomass produced high-quality imprint images of pillar patterns with a 230-nm diameter. Ecofriendly antiglare film with liquid glucose and trehalose derivatives derived from biomass was indicated to achieve the real refraction index of 1.45 to 1.53 at 350 to 800 nm, low imaginary refractive index of <0.005 and low volumetric shrinkage of 4.8% during ultraviolet irradiation. A distinctive bulky glucose structure in glucose and trehalose derivatives was considered to be effective for minimizing the volumetric shrinkage of resist film during ultraviolet irradiation, in addition to suitable optical properties for high-definition display.

Mercuric iodate precipitation from radioiodine-containing off-gas scrubber solution

DOEpatents

Partridge, Jerry A.; Bosuego, Gail P.

1982-01-01

Mercuric nitrate-nitric acid scrub solutions containing radioiodine may be reduced in volume without excessive loss of volatile iodine. The use of concentrated nitric acid during an evaporation process oxidizes the mercury-iodide complex to a less volatile mercuric iodate precipitate.

Radioiodinated branched carbohydrates

DOEpatents

Goodman, Mark M.; Knapp, Jr., Furn F.

1989-01-01

A radioiodinated branched carbohydrate for tissue imaging. Iodine-123 is stabilized in the compound by attaching it to a vinyl functional group that is on the carbohydrate. The compound exhibits good uptake and retention and is promising in the development of radiopharmaceuticals for brain, heart and tumor imaging.

SPECT/CT localization of oral radioiodine activity: a retrospective study and in-vitro assessment

PubMed Central

Burlison, Jared S.; Hartshorne, Michael F.; Voda, Alan M.; Cocks, Franklin H.

2013-01-01

Purpose We sought to further localize radioiodine activity in the mouth on post-thyroid cancer therapy imaging using single-photon emission computed tomography/computed tomography (SPECT/CT). Materials and methods We retrospectively reviewed all patients (58) who underwent thyroid cancer therapy with iodine-131 (131I) at our institution from August 2009 to March 2011 whose post-therapy radioiodine imaging included neck SPECT/CT. A small group (six) of diagnostic 123I scans including SPECT/CT was also reviewed. Separately, we performed in-vitro 131I (sodium iodide) binding assays with amalgam and Argenco HP 77 (77% dental gold alloy) as proof of principle for these interactions. Results Of the 58 post-therapy patients, 45 (78%) had undergone metallic dental restorations, and of them 41 (91%) demonstrated oral 131I activity localizing preferentially to those restorations. It was observed that radioiodine also localized to other dental restorations and to orthodontic hardware. Gum-line activity in edentulous patients suggests radioiodine interaction with denture adhesive. In vitro, dental amalgam and Argenco HP 77 bound 131I in a time-dependent manner over 1–16 days of exposure. Despite subsequent washings with normal saline, significant 131I activity (maximally 12% for amalgam and 68% for Argenco HP 77) was retained by these metals. Subsequent soaking in a saturated solution of potassium iodide partially displaced 131I from amalgam, with near-total displacement of 131I from Argenco HP 77. Conclusion SPECT/CT shows that radioiodine in the oral cavity localizes to metallic dental restorations. Furthermore, in-vitro studies demonstrate partially reversible binding of 131I to common dental metals. PMID:24128897

Clinical outcomes after estimated versus calculated activity of radioiodine for the treatment of hyperthyroidism: systematic review and meta-analysis.

PubMed

de Rooij, A; Vandenbroucke, J P; Smit, J W A; Stokkel, M P M; Dekkers, O M

2009-11-01

Despite the long experience with radioiodine for hyperthyroidism, controversy remains regarding the optimal method to determine the activity that is required to achieve long-term euthyroidism. To compare the effect of estimated versus calculated activity of radioiodine in hyperthyroidism. Design Systematic review and meta-analysis. We searched the databases Medline, EMBASE, Web of Science, and Cochrane Library for randomized and nonrandomized studies, comparing the effect of activity estimation methods with dosimetry for hyperthyroidism. The main outcome measure was the frequency of treatment success, defined as persistent euthyroidism after radioiodine treatment at the end of follow-up in the dose estimated and calculated dosimetry group. Furthermore, we assessed the cure rates of hyperthyroidism. Three randomized and five nonrandomized studies, comparing the effect of estimated versus calculated activity of radioiodine on clinical outcomes for the treatment of hyperthyroidism, were included. The weighted mean relative frequency of successful treatment outcome (euthyroidism) was 1.03 (95% confidence interval (CI) 0.91-1.16) for estimated versus calculated activity; the weighted mean relative frequency of cure of hyperthyroidism (eu- or hypothyroidism) was 1.03 (95% CI 0.96-1.10). Subgroup analysis showed a relative frequency of euthyroidism of 1.03 (95% CI 0.84-1.26) for Graves' disease and of 1.05 (95% CI 0.91-1.19) for toxic multinodular goiter. The two main methods used to determine the activity in the treatment of hyperthyroidism with radioiodine, estimated and calculated, resulted in an equally successful treatment outcome. However, the heterogeneity of the included studies is a strong limitation that prevents a definitive conclusion from this meta-analysis.

Materials and processes for the effective capture and immobilization of radioiodine: A review

DOE PAGES

Riley, Brian J.; Vienna, John D.; Strachan, Denis M.; ...

2015-12-02

In this study, the immobilization of radioiodine produced from reprocessing used nuclear fuel is a growing priority for research and development of nuclear waste forms. This review provides a comprehensive summary of the current issues surrounding processing and containment of 129I, the isotope of greatest concern due to its long half-life of 1.6 × 10 7 y and potential incorporation into the human body. Strategies for disposal of radioiodine, captured by both wet scrubbing and solid sorbents, are discussed, as well as potential iodine waste streams for insertion into an immobilization process. Next, consideration of direct disposal of salts, incorporationmore » into glasses, ceramics, cements, and other phases is discussed. The bulk of the review is devoted to an assessment of various sorbents for iodine and of waste forms described in the literature, particularly inorganic minerals, ceramics, and glasses. This review also contains recommendations for future research needed to address radioiodine immobilization materials and processes.« less

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

PubMed

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.

EANM Dosimetry Committee series on standard operational procedures for pre-therapeutic dosimetry II. Dosimetry prior to radioiodine therapy of benign thyroid diseases.

PubMed

Hänscheid, Heribert; Canzi, Cristina; Eschner, Wolfgang; Flux, Glenn; Luster, Markus; Strigari, Lidia; Lassmann, Michael

2013-07-01

The EANM Dosimetry Committee Series "Standard Operational Procedures for Pre-Therapeutic Dosimetry" (SOP) provides advice to scientists and clinicians on how to perform patient-specific absorbed dose assessments. This particular SOP describes how to tailor the therapeutic activity to be administered for radioiodine therapy of benign thyroid diseases such as Graves' disease or hyperthyroidism. Pretherapeutic dosimetry is based on the assessment of the individual (131)I kinetics in the target tissue after the administration of a tracer activity. The present SOP makes proposals on the equipment to be used and guides the user through the measurements. Time schedules for the measurement of the fractional (131)I uptake in the diseased tissue are recommended and it is shown how to calculate from these datasets the therapeutic activity necessary to administer a predefined target dose in the subsequent therapy. Potential sources of error are pointed out and the inherent uncertainties of the procedures depending on the number of measurements are discussed. The theoretical background and the derivation of the listed equations from compartment models of the iodine kinetics are explained in a supplementary file published online only.

Mixed species radioiodine air sampling readout and dose assessment system

DOEpatents

Distenfeld, Carl H.; Klemish, Jr., Joseph R.

1978-01-01

This invention provides a simple, reliable, inexpensive and portable means and method for determining the thyroid dose rate of mixed airborne species of solid and gaseous radioiodine without requiring highly skilled personnel, such as health physicists or electronics technicians. To this end, this invention provides a means and method for sampling a gas from a source of a mixed species of solid and gaseous radioiodine for collection of the mixed species and readout and assessment of the emissions therefrom by cylindrically, concentrically and annularly molding the respective species around a cylindrical passage for receiving a conventional probe-type Geiger-Mueller radiation detector.

Human radiation studies: Remembering the early years. Oral history of Dr. Nadine Foreman, M.D., August 19, 1994

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1995-07-01

Dr. Nadine Foreman was interviewed by representatives of the US DOE Office of Human Radiation Experiments (OHRE). Dr. Foreman was selected for interview because of the position she held at the University of California, San Francisco. Following a brief biographical sketch, Dr. Foreman describes her work with Dr. Mayo Soley using I-131 in treatment of hyperthyroidism, selection criteria for patients in the radioiodine project, work with Dr. Earl Miller, work at Highland Hospital, radioiodine treatment of diffuse toxic goiter (myxedema), the radiophosphorus and radioiodine programs with Dr. Bert Low-Beer, and treatment of polycythemia vera.

[Structural and functional status of the hypophyseal-thyroid system in prenatally irradiated children].

PubMed

Makiienko, T S; Pavliuk, V P; Pavliuk, I V; Mosiienko, A P

2001-01-01

In order to evaluate the morphologic-and-functional state of the hypophysis-thyroid system long after the Chernobyl accident we examined 1491 children from the northern territories of the Zhitomir region. Of these, 261 had not been in utero exposed to radioiodine, 1230 pediatric subjects proved to be postconception-exposed. In utero radioiodine has not been found to affect the thyroid size in any noticeable way. The degree of structural-and-functional indices for the thyreostat system in prenatally irradiated children depends on the stage of the thyroid development just when there happened to be an exposure to radioiodine.

[Role of iodine-131 in the management of differentiated thyroid cancers (vesicular origin)].

PubMed

Boughattas, Sami; Hassine, Habib; Chatti, Kaouther; Letaief, Bechir; Jomaa, Rached; Essabbah, Habib

2002-08-01

Radioodine-131 has an important place in the management of well-differentiated thyroid cancer. Patient preparation for radioiodine-131 administration must be rigorous and is based on the stimulation of endogenous TSH production, which requires a hypothyroid state after withdrawal of suppressive T4-therapy. The introduction of recombinant human TSH would simplify the protocol of preparation and improve the quality of life of patients. The diagnosis place of radioiodine-131 knew significant changes following the introduction of the serum thyroglobulin measurement. This tumour marker has a central role in the strategy of follow-up and tends to be the principal element of indication for a diagnosis exploration with radioidine-131. The systematic ablation of thyroid remnants remains controversial particularly in patients with good prognosis factors; the efficacy of low activities is also still debatable. The optimal follow-up strategy and the indication of remnant ablation must take in account the prognosis factors of survival and recurrence. Radioiodine-131 therapy permits frequently the cure of distant metastases, particularly in infraradiological pulmonary forms. This fact outlines the importance of an early detection of tumour recurrence based on the conjunction of radioiodine-131 and thyroglobulin. Side effects of radioiodine-131 therapy are generally limited if the precautionary measures are well applied; leukaemia constitutes the main risk but this complication is very uncommon and occurs after a high cumulative activity.

Defects in iodide metabolism in thyroid cancer and implications for the follow-up and treatment of patients.

PubMed

Schlumberger, Martin; Lacroix, Ludovic; Russo, Diego; Filetti, Sebastiano; Bidart, Jean-Michel

2007-03-01

The two major steps of iodine metabolism--uptake and organification--are altered in thyroid cancer tissues. Organification defects result in a rapid discharge of radioiodine from thyroid cells, a short effective half-life of iodine, and a low rate of thyroid hormone synthesis. These defects are mainly due to decreased expression of functional genes encoding the sodium-iodide symporter and thyroid peroxidase and could result in a low radiation dose to thyroid cancer cells. TSH stimulation that is achieved with injections of recombinant human TSH, or long-term withdrawal of thyroid hormone treatment increases iodine-131 uptake in two-thirds of patients with metastatic disease and increases thyroglobulin production in all patients with metastases, even in the absence of detectable uptake. Serum thyroglobulin determination obtained following TSH stimulation and neck ultrasonography is the most sensitive combination for the detection of small tumor foci. Radioiodine treatment is effective when a high radiation dose can be delivered (in patients with high uptake and retention of radioiodine) and when tumor foci are sensitive to the effects of radiation therapy (younger patients, with a well-differentiated tumor and/or with small metastases). The other patients rarely respond to radioiodine treatment, and when progression occurs, other treatment modalities should be considered. Novel strategies are currently being explored to restore iodine uptake in cancer cells that are unable to concentrate radioiodine.

A review of countermeasures to reduce radioiodine in milk of dairy animals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Howard, B.J.; Voigt, G.; Segal, M.G.

1996-11-01

The most effective countermeasure for radioiodine contamination of milk is to provide dairy animals with uncontaminated feed, with the added advantage that it will be effective for other radionuclides in the fallout. Another effective response is to process the milk into storable dairy products for an appropriate length of time to allow for physical decay. The use of additives given to ruminants to reduce radioiodine in milk is an alternative countermeasure which could be effective. Stable iodine administration is a practically feasible option which has the potential to reduce radioiodine levels in milk by at most a factor of three.more » Stable iodine supplementation should be at sufficiently high rates to be effective (and at least 1 g d{sup {minus}1} for dairy cows), particularly for ruminants already receiving high amounts of iodine in the diet. Currently available data are inadequate to recommend a suitable stable iodine administration rate for different species of ruminants. Other compounds, such as perchlorate and thiocyanate, also reduce the transfer to radioiodine to milk (and thyroid). Some of these compounds seem to be potentially equally as effective as stable iodine. However, currently there is inadequate information on their effectiveness and possible toxicity to both ruminants and humans for these compounds to be considered as suitable countermeasure additives. 85 refs., 2 figs., 3 tabs.« less

Guidelines for the use of radioiodine in the management of hyperthyroidism: a summary. Prepared by the Radioiodine Audit Subcommittee of the Royal College of Physicians Committee on Diabetes and Endocrinology, and the Research Unit of the Royal College of Physicians.

PubMed

Lazarus, J H

1995-01-01

Radioiodine (131I) therapy is indicated in patients with nearly all causes of hyperthyroidism. It may safely be given to patients of all age groups but is less often given to children under 10 years old. It is completely contraindicated in pregnancy and while breast feeding, but there is no increased risk of thyroid cancer, leukaemia or solid tumours. Administration of radioiodine must conform to regulations and definitions laid down by ARSAC And POPUMET. Medical staff authorising therapy must hold an ARSAC licence. The recommended strategy is to give an activity sufficient to render the patient rapidly euthyroid and maintain that state or achieve no more than a low rate of hypothyroidism in subsequent years. A range of activity (300-800 MBq) is suggested depending on the clinical state. Antithyroid drugs may be given before or after (or both) radioiodine if necessary. Full written information should be given to the patient and written consent obtained. A structured follow-up should be used ensuring regular measurement of TSH or FT4. Close cooperation with the patient's general practitioner is recommended throughout the assessment, treatment and follow-up. Shared care with a computer based follow-up system is recommended.

131I therapy of thyroid cancer patients.

PubMed

Reiners, C; Farahati, J

1999-12-01

Thyroid cancer is a rare malignancy with wide interethnic and geographic variations. In Germany thyroid carcinoma is the 13th most frequent malignancy (2.7 new cases yearly per 100,000 inhabitants). The overall temporal incidence is increasing slightly in recent years. The most common types of cancer are papillary (60-80%) and follicular cancers (10-20%). The relevant prognostic indicators are tumor stage and distant metastases. The mean survival rates in papillary thyroid cancer usually exceed 90%, whereas in follicular thyroid cancer they amount to approximately 80%. The standard treatment procedure in differentiated papillary and follicular thyroid cancer consists of total thyroidectomy followed by adjuvant ablative therapy with radioiodine. Only in papillary thyroid cancer stage pT1N0M0 lobectomy alone is considered to be appropriate. In patients with locally invasive differentiated thyroid cancers stage pT4 adjuvant percutaneous radiation therapy is a treatment option. Radioiodine therapy has to be performed under the stimulative influence of TSH. Usually TSH suppressive medication with Levothyroxine has to be withdrawn approximately 4 weeks prior to radioiodine therapy. In the future, exogenous stimulation by recombinant TSH may be used instead of thyroid hormone withdrawal. It has been proven by different studies that ablative radioiodine therapy reduces the frequency of recurrences and tumor spread in patients with thyroid cancer significantly. In patients with distant metastases, up to 50% of complete responses may be achieved with radioiodine treatment.

Novel fungal FAD glucose dehydrogenase derived from Aspergillus niger for glucose enzyme sensor strips.

PubMed

Sode, Koji; Loew, Noya; Ohnishi, Yosuke; Tsuruta, Hayato; Mori, Kazushige; Kojima, Katsuhiro; Tsugawa, Wakako; LaBelle, Jeffrey T; Klonoff, David C

2017-01-15

In this study, a novel fungus FAD dependent glucose dehydrogenase, derived from Aspergillus niger (AnGDH), was characterized. This enzyme's potential for the use as the enzyme for blood glucose monitor enzyme sensor strips was evaluated, especially by investigating the effect of the presence of xylose during glucose measurements. The substrate specificity of AnGDH towards glucose was investigated, and only xylose was found as a competing substrate. The specific catalytic efficiency for xylose compared to glucose was 1.8%. The specific activity of AnGDH for xylose at 5mM concentration compared to glucose was 3.5%. No other sugars were used as substrate by this enzyme. The superior substrate specificity of AnGDH was also demonstrated in the performance of enzyme sensor strips. The impact of spiking xylose in a sample with physiological glucose concentrations on the sensor signals was investigated, and it was found that enzyme sensor strips using AnGDH were not affected at all by 5mM (75mg/dL) xylose. This is the first report of an enzyme sensor strip using a fungus derived FADGDH, which did not show any positive bias at a therapeutic level xylose concentration on the signal for a glucose sample. This clearly indicates the superiority of AnGDH over other conventionally used fungi derived FADGDHs in the application for SMBG sensor strips. The negligible activity of AnGDH towards xylose was also explained on the basis of a 3D structural model, which was compared to the 3D structures of A. flavus derived FADGDH and of two glucose oxidases. Copyright © 2016 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kamel, R.S.; Landon, J.; Smith, D.S.

Nortriptyline derivatives prepared by reaction with fluorescein isothiocyanate or conjugation to N-acetyl-L-histidine were radioiodinated and the products purified with Sephadex LH-20 columns to obtain two novel nortriptyline radioligands. Antisera were raised in rabbits by immunization with nortriptyline conjugated to succinylated ovine albumin. By use of the iodinated fluorescein derivative we developd a liquid-phase second-antibody radioimmunoassay that gives results correlating closely (r = 0.98) with those by an established radioimmunoassay of similar specificity in the assay of apparent total amitriptyline and its metabolite nortriptyline in serum or plasma from patients being treated with these drugs. With the iodinated N-acetyl-L-histidin derivative wemore » developed a magnetizable solid-phase second-antibody radioimmunoassay. The cross reactivities of amitriptyline and nortriptyline could be made equal by performing the assay at pH 9.0, which makes it possible to measure true total active drug concentrations in patients receiving amitriptyline.« less

Evidence of extensive plasma glucose recycling following a glucose load in seabass.

PubMed

Rito, João; Viegas, Ivan; Pardal, Miguel A; Jones, John G

2017-09-01

Seabass and other carnivorous fish are highly dependent on gluconeogenesis from dietary amino acids to maintain glycemia. Glucose recycling (glucose→C3-intermediate→glucose) may potentiate the effects of glucose administration in sparing amino acid gluconeogenesis. To date, very few measurements of glucose recycling have been reported in fish. Thus, to determine the extent of glucose recycling following a glycemic challenge, juvenile seabass were given an intraperitoneal glucose load (2gkg -1 ) enriched with [U- 13 C]glucose. 13 C NMR analysis of plasma glucose 13 C-isotopomers was used to determine the fractional contributions of glucose derived directly from the load versus that from glucose recycling at 48h after the load. Both fed and 21-day fasted fish (20 per condition) were studied. In fasted fish, 18±4% of plasma glucose was directly derived from the load while 13±2% was derived from glucose recycling. In fed fish, the load accounted for 6±1% of plasma glucose levels while glucose recycling contributed 16±4%. 13 C NMR analysis of plasma lactate revealed 13 C-isotopomers corresponding to the expected C3-intermediates of peripheral [U- 13 C]glucose catabolism indicating that circulating lactate was a key intermediate in glucose carbon recycling under these conditions. In conclusion, glucose recycling was shown to contribute a significant portion of plasma glucose levels in both fed and fasted seabass 48h after an intraperitoneal glucose challenge and circulating lactate was shown to be an intermediate of this pathway. Copyright © 2017. Published by Elsevier Inc.

Generation of glucose-responsive, insulin-producing cells from human umbilical cord blood-derived mesenchymal stem cells.

PubMed

Prabakar, Kamalaveni R; Domínguez-Bendala, Juan; Molano, R Damaris; Pileggi, Antonello; Villate, Susana; Ricordi, Camillo; Inverardi, Luca

2012-01-01

We sought to assess the potential of human cord blood-derived mesenchymal stem cells (CB-MSCs) to derive insulin-producing, glucose-responsive cells. We show here that differentiation protocols based on stepwise culture conditions initially described for human embryonic stem cells (hESCs) lead to differentiation of cord blood-derived precursors towards a pancreatic endocrine phenotype, as assessed by marker expression and in vitro glucose-regulated insulin secretion. Transplantation of these cells in immune-deficient animals shows human C-peptide production in response to a glucose challenge. These data suggest that human cord blood may be a promising source for regenerative medicine approaches for the treatment of diabetes mellitus.

Interaction of free arginine and guanidine with glucose under thermal processing conditions and formation of Amadori-derived imidazolones.

PubMed

Zhu, Yuchen; Yaylayan, Varoujan A

2017-04-01

To investigate the reactivity of free guanidine and arginine in the formation of imidazolinone derivatives, model systems of guanidine or arginine/glucose or 13 [C-6]-glucose were heated in aqueous solutions at110°C for 3h and the residues were analyzed by ESI/qTOF/MS using MS/MS and isotope labeling techniques. The analysis of the data indicated that guanidine and arginine formed both covalent and non-covalent interaction products. Covalent interactions included Amadori rearrangement at the α-nitrogen with glucose and imidazolinone formation with 3-deoxy-glucosone at the guanidine side-chain. Non-covalent interactions, such as self-interaction and interaction with free guanidine or arginine and glucose, were also observed. Guanidine underwent three sequential Amadori rearrangements and the free and mono-glycated guanidine also formed imidazolinone derivatives and their corresponding dehydration products and at the same time exhibiting various non-covalent interactions. On the other hand, arginine formed free Amadori product, free imidazolinone and Amadori-derived imidazolinone derivative in addition to methylglyoxal-derived hydroimidazolones. Copyright © 2016 Elsevier Ltd. All rights reserved.

[The radioiodine test for the evaluation of iodine deficiency in the district of Karl-Marx-Stadt and in East Germany].

PubMed

Bauch, K; Weiss, O; Möckel, G; Gerlach, J; Seitz, W; Ulrich, F E; Dempe, A

1981-10-01

The values of the per cent 24 h radioiodine uptake in the GDR are above 60--70% and speak for a low alimentary intake of iodine or renal excretion of iodine below 40 micrograms J/d. Like the struma prevalences they show a tendency increasing from north to south and characterize the whole European situation of iodine deficiency including its decrease from west to east. The mean values of radioiodine uptake of 71.7 +/- 13.2% (n = 110) in euthyroids of the district of Karl-Marx-Stadt correspond to the iodine deficiency as it occurs approximately in the districts of Erfurt, Dresden, Munich or Freiburg/B. The alimentary iodine intake of 38.4 +/- 17.2 micrograms J/d and the renal iodine excretion of 29.9 +/- 16.1 micrograms J/d, calculated from the 24 h radioiodine accumulation values of 40 euthyroid persons by means of a mathematical model developed by Oddie and co-workers were low. The latter only slightly differed (P less than 0.05) from its chemically estimated excretion of iodine in the urine: 23.1 +/- 16.9 micrograms J/g creatinine (n = 73). Between the calculated and chemically estimated excretion of iodine there was a relatively strict correlation of r = 0.68 (n = 26; P less than 0.001). The introduction of an iodine prophylaxis is regarded as an urgent necessity. Later on a new estimation of the regional "normal values" is necessary for the per cent radioiodine uptake.

Limits of fetal thyroid risk from radioiodine exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lloyd, R.D.; Tripp, D.A.; Kerber, R.A.

1996-04-01

An incident in which a young women became pregnant soon after being treated with 444 MBq {sup 131}I for Graves disease prompted us to search local records for the occurrence of thyroid abnormalities among people exposed in utero to fallout radioiodine. The data base from the Utah Fallout Study indicated that there had been 480 cohort subjects for whom dose to thyroid from fallout radioiodine had been calculated and who could have received any thyroid dose before birth (2473 subjects had been re-examined in 1985-86 of the 4818 examined in 1965-70). Of these 480 subjects in this category, 403 ofmore » them could be located in the 1980`s and were examined for abnormalities. Although nodules, thyroiditis, hypothyroidism and goiter were seen among the 375 persons with in utero thyroid doses from fallout radioiodine below 0.42 Gy, no thyroid abnormalities of any kind occurred in the 4 persons with in utero thyroid doses of 0.5 to 2.6 Gy. In addition, no neoplasia was found in any of the 403 subjects examined about 3 decades after in utero fallout exposure. These limited data do not indicate that the fetal thyroid is more sensitive than the postnatal thyroid by more than about a factor of about 4 when thyroid dose is considered and by not much more than unity when the comparison is based on dose equivalent (x-ray vs. radioiodine). 21 refs., 1 tab.« less

Effect of specific activity on organ uptake of iodine-123-meta-iodobenzylguanidine in humans.

PubMed

Farahati, J; Lassmann, M; Scheubeck, M; Bier, D; Hanscheid, H; Schelper, L; Grelle, I; Biko, J; Werner, E; Graefe, K; Reiners, C

1997-04-01

Radioiodinated meta-iodobenzylguanidine (MIBG), an analogue of norepinephrine, has been used in management of neuroendocrine tumors. Recent studies reveal that distribution of radioiodinated MIBG in animals depends on the specific activity of this radiopharmaceutical. In order to clarify the effect of specific activity on organ uptake of radioiodinated MIBG. the kinetics of no-carrier-added (n.c.a.) [I-123]MIBG (greater than or equal to 7.4 TBq/mu mol) were compared with those of commercial (com.) [I-123]MIBG (similar to 74 MBq/mu mol) in 3 healthy volunteers by serial imaging and blood sampling. The organ uptake of radioiodinated MIBG did not remarkably differ between the two specific activities. Due to rapid degradation a more pronounced accumulation of radioactivity was present in plasma alter n.c.a. than after com. [I-123]MIBG resulting in a higher background and thyroid activity. In addition due to a prolonged residence time of the radioactivity, the radiation exposure to organs was in general slightly higher with n.c.a. [I-123]MIBG as compared to com. [I-123]MIBG. This finding highlights the higher in vivo deiodination of n.c.a. [I-123]MIBG than of com. [I-123]MIBG in humans. In the treatment of children suffering from neuroblastoma, therefore, degradation of n.c.a. [I-123]MIBG may decrease the concentration of radioiodinated MIBG available for binding at tumor sites and result in higher radiation exposure of non-tumor tissue.

Hybrid Vision-Fusion system for whole-body scintigraphy.

PubMed

Barjaktarović, Marko; Janković, Milica M; Jeremić, Marija; Matović, Milovan

2018-05-01

Radioiodine therapy in the treatment of differentiated thyroid carcinoma (DTC) is used in clinical practice for the ablation of thyroid residues and/or destruction of tumour tissue. Whole-body scintigraphy for visualization of the spatial 131I distribution performed by a gamma camera (GC) is a standard procedure in DTC patients after application of radioiodine therapy. A common problem is the precise topographic localization of regions where radioiodine is accumulated even in SPECT imaging. SPECT/CT can provide precise topographic localization of regions where radioiodine is accumulated, but it is often unavailable, especially in developing countries because of the high price of the equipment. In this paper, we present a Vision-Fusion system as an affordable solution for 1) acquiring an optical whole-body image during routine whole-body scintigraphy and 2) fusing gamma and optical images (also available for the auto-contour mode of GC). The estimated prediction error for image registration is 1.84 mm. The validity of fusing was tested by performing simultaneous optical and scintigraphy image acquisition of the bar phantom. The fusion result shows that the fusing process has a slight influence and is lower than the spatial resolution of GC (mean value ± standard deviation: 1.24 ± 0.22 mm). The Vision-Fusion system was used for radioiodine post-therapeutic treatment, and 17 patients were followed (11 women and 6 men, with an average age of 48.18 ± 13.27 years). Visual inspection showed no misregistration. Based on our first clinical experience, we noticed that the Vision-Fusion system could be very useful for improving the diagnostic possibility of whole-body scintigraphy after radioiodine therapy. Additionally, the proposed Vision-Fusion software can be used as an upgrade for any GC to improve localizations of thyroid/tumour tissue. Copyright © 2018 Elsevier Ltd. All rights reserved.

Measurement of gluconeogenesis using glucose fragments and mass spectrometry after ingestion of deuterium oxide.

USDA-ARS?s Scientific Manuscript database

We report a new method to measure the fraction of glucose derived from gluconeogenesis using gas chromatography-mass spectrometry and positive chemical ionization. After ingestion of deuterium oxide by subjects, glucose derived from gluconeogenesis is labeled with deuterium. Our calculations of gluc...

MicroSPECT imaging of triple negative breast cancer cell tumor xenografted in athymic mice with radioiodinated anti-ICAM-1 monoclonal antibody.

PubMed

You, Linyi; Wang, Xiangyu; Guo, Zhide; Zhang, Deliang; Zhang, Pu; Li, Jindian; Su, Xinhui; Pan, Weimin; Zhang, Xianzhong

2018-04-04

Intercellular adhesion molecule-1(ICAM-1) is a potential molecular target and biomarker for triple negative breast cancer (TNBC) therapy and diagnosis. In this study, aICAM-1 was radioiodinated with 125 I/ 131 I in high radiochemical yield and the probes for TNBC tumor targeting and radioimmunotherapy were evaluated in tumor-bearing mice. High and specific accumulation of 125 I-aICAM1 in TNBC MDA-MB-231 tumor was observed in SPECT imaging and the tumor grew was inhibited obviously by 131 I-aICAM1. Thus, the radioiodinated aICAM1 could serve as potential agents for TNBC theranostics. Copyright © 2018 Elsevier Ltd. All rights reserved.

Complete oxidative conversion of lignocellulose derived non-glucose sugars to sugar acids by Gluconobacter oxydans.

PubMed

Yao, Ruimiao; Hou, Weiliang; Bao, Jie

2017-11-01

Non-glucose sugars derived from lignocellulose cover approximately 40% of the total carbohydrates of lignocellulose biomass. The conversion of the non-glucose sugars to the target products is an important task of lignocellulose biorefining research. Here we report a fast and complete conversion of the total non-glucose sugars from corn stover into the corresponding sugar acids by whole cell catalysis and aerobic fermentation of Gluconobacter oxydans. The conversions include xylose to xylonate, arabinose to arabonate, mannose to mannonate, and galactose to galactonate, as well as with glucose into gluconate. These cellulosic non-glucose sugar acids showed the excellent cement retard setting property. The mixed cellulosic sugar acids could be used as cement retard additives without separation. The conversion of the non-glucose sugars not only makes full use of lignocellulose derived sugars, but also effectively reduces the wastewater treatment burden by removal of residual sugars. Copyright © 2017 Elsevier Ltd. All rights reserved.

Radioiodine Labeled Anti-MIF McAb: A Potential Agent for Inflammation Imaging

PubMed Central

Zhang, Chao; Hou, Gui-hua; Han, Jian-kui; Song, Jing; Liang, Ting

2007-01-01

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that may play a role in the pathogenesis of inflammation. Radiolabeled anti-MIF McAb can be used to detect in vivo inflammatory changes. The objective of this study was to investigate in vivo biology of radioiodinated anti-MIF McAb using the inflammation model mice. Anti-MIF McAb was radioiodinated with NaI125 by Iodogen method. Animal models were induced in the mice by intramuscular injection of S. aureus, E. coli, and turpentine oil. The biodistribution studies with radioiodinated anti-MIF McAb were performed on inflammation mice. The relationship between inflammatory lesions and anti-MIF McAb binding was investigated using the percent of injected dose per gram tissue (% ID/g) of tissue samples and whole-body autoradiography. The radioactivity of I125-anti-MIF McAb in the inflammatory tissue increased gradually for three inflammation models. The highest uptake was found in S. aureus group and the lowest was in E. coli group. The uptake in turpentine oil group was average. Whole-body autoradiography showed that all inflammation foci could be visualized clearly from 24 hours after injection, but 48 hours images were much clearer in accordance with the high T/NT ratio. These results demonstrate the ability of radioiodinated anti-MIF McAb to measure in vivo inflammatory events represented by high expression of MIF and suggests that radiolabeled anti-MIF McAb warrants further investigation as a potential inflammation-seeking agent for imaging to detect inflammatory disorders. PMID:18317509

Lithium carbonate pre-treatment in 131-I therapy of hyperthyroidism.

PubMed

Płazińska, Maria Teresa; Królicki, Leszek; Bąk, Marianna

2011-01-01

The aim of the present work was to investigate the influence of lithium carbonate on the kinetics of radioiodine in the thyroid gland, and the long-lasting effect of radioiodine therapy pre-treated with lithium carbonate in patients with different types of hyperthyreosis and low baseline 24-h thyroidal radioactive iodine uptake (RAIU). The examinations were performed in two groups of patients: in a control group with RAIU 〉 30% and in patients with RAIU 〈 30%. All groups were comparable with regard to age, sex, duration and type of disease (Graves' disease, autonomous node, multinodular goitre). The control group was treated (without lithium) according to described protocol. The second group was pre-treated with lithium carbonate in a dose of 1.0 g/day for 6 days before radioiodine and 3 days thereafter. A significant increase in iodide uptake in the thyroid gland was observed during intake of lithium carbonate in 106 out of 128 patients. A decrease of T(3), FT(3), T(4), and FT(4) levels and no significant changes in concentration of TSH were observed as an effect of lithium carbonate treatment. Three years of follow-up show that the results of radioiodine therapy with short lasting lithium carbonate intake are better in the first year and are similar in the second and third years in comparison to the control group. Lithium pre-treatment in hyperthyroid patients with low baseline uptake of radioiodine can increase iodine retention in the thyroid gland independently of the primary disease and permits the use of lower doses of radiation in the therapy.

Tinea corporis overlying the thyroid gland after radioiodine (131I) treatment of Graves' disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moreno, A.J.; Hartshorne, M.F.; Yedinak, M.A.

1986-04-01

A case of tinea corporis involving the skin overlying the thyroid gland is described in a 36-year-old man who had received radioiodine treatment for Graves' disease. The dermatophytosis mimicked a delayed roentgen erythema. Radiation to the dermis may have locally altered the cell-mediated immunity and predisposed this patient to the dermatophytosis.

New steroid derivative with hypoglycemic activity

PubMed Central

Lauro, Figueroa-Valverde; Francisco, Díaz-Cedillo; Lenin, Hau-Heredia; Elodia, García-Cervera; Eduardo, Pool-Gómez; Marcela, Rosas-Nexticapa; Bety, Sarabia-Alcocer

2014-01-01

Data indicates that some steroid derivatives may induce changes on glucose levels; nevertheless, data are very confusing. Therefore, more pharmacological data are needed to characterize the activity induced by the steroid derivatives on glucose levels. The aim of this study was to synthesize a new steroid derivative for evaluate its hypoglycemic activity. The effects of steroid derivative on glucose concentration were evaluated in a diabetic animal model using glibenclamide and metformin as controls. In addition, the pregnenolone-dihydrotestosterone conjugate was bound to Tc-99m using radioimmunoassay methods, to evaluate the pharmacokinetics of the steroid derivative over time. The results showed that the pregnenolone-dihydrotestosterone conjugate induces changes on the glucose levels in similar form than glibenclamide. Other data showed that the biodistribution of Tc-99m-steroid derivativein brain was higher in comparison with spleen, stomach, intestine liver and kidney. In conclusion, the pregnenolone-dihydrotestosterone conjugate exerts hypoglycemic activity and this phenomenon could depend of its physicochemical properties which could be related to the degree of lipophilicity of the steroidderivative. PMID:25550906

Brain-derived neurotrophic factor in the nucleus tractus solitarii modulates glucose homeostasis after carotid chemoreceptor stimulation in rats.

PubMed

Montero, Sergio; Cuéllar, Ricardo; Lemus, Mónica; Avalos, Reyes; Ramírez, Gladys; de Álvarez-Buylla, Elena Roces

2012-01-01

Neuronal systems, which regulate energy intake, energy expenditure and endogenous glucose production, sense and respond to input from hormonal related signals that convey information from body energy availability. Carotid chemoreceptors (CChr) function as sensors for circulating glucose levels and contribute to glycemic counterregulatory responses. Brain-derived neurotrophic factor (BDNF) that plays an important role in the endocrine system to regulate glucose metabolism could play a role in hyperglycemic glucose reflex with brain glucose retention (BGR) evoked by anoxic CChr stimulation. Infusing BDNF into the nucleus tractus solitarii (NTS) before CChr stimulation, showed that this neurotrophin increased arterial glucose and BGR. In contrast, BDNF receptor (TrkB) antagonist (K252a) infusions in NTS resulted in a decrease in both glucose variables.

Physical activity measured by physical activity monitoring system correlates with glucose trends reconstructed from continuous glucose monitoring.

PubMed

Zecchin, Chiara; Facchinetti, Andrea; Sparacino, Giovanni; Dalla Man, Chiara; Manohar, Chinmay; Levine, James A; Basu, Ananda; Kudva, Yogish C; Cobelli, Claudio

2013-10-01

In type 1 diabetes mellitus (T1DM), physical activity (PA) lowers the risk of cardiovascular complications but hinders the achievement of optimal glycemic control, transiently boosting insulin action and increasing hypoglycemia risk. Quantitative investigation of relationships between PA-related signals and glucose dynamics, tracked using, for example, continuous glucose monitoring (CGM) sensors, have been barely explored. In the clinic, 20 control and 19 T1DM subjects were studied for 4 consecutive days. They underwent low-intensity PA sessions daily. PA was tracked by the PA monitoring system (PAMS), a system comprising accelerometers and inclinometers. Variations on glucose dynamics were tracked estimating first- and second-order time derivatives of glucose concentration from CGM via Bayesian smoothing. Short-time effects of PA on glucose dynamics were quantified through the partial correlation function in the interval (0, 60 min) after starting PA. Correlation of PA with glucose time derivatives is evident. In T1DM, the negative correlation with the first-order glucose time derivative is maximal (absolute value) after 15 min of PA, whereas the positive correlation is maximal after 40-45 min. The negative correlation between the second-order time derivative and PA is maximal after 5 min, whereas the positive correlation is maximal after 35-40 min. Control subjects provided similar results but with positive and negative correlation peaks anticipated of 5 min. Quantitative information on correlation between mild PA and short-term glucose dynamics was obtained. This represents a preliminary important step toward incorporation of PA information in more realistic physiological models of the glucose-insulin system usable in T1DM simulators, in development of closed-loop artificial pancreas control algorithms, and in CGM-based prediction algorithms for generation of hypoglycemic alerts.

Association between blood glucose level derived using the oral glucose tolerance test and glycated hemoglobin level.

PubMed

Kim, Hyoung Joo; Kim, Young Geon; Park, Jin Soo; Ahn, Young Hwan; Ha, Kyoung Hwa; Kim, Dae Jung

2016-05-01

Glycated hemoglobin (HbA1c) is widely used as a marker of glycemic control. Translation of the HbA1c level to an average blood glucose level is useful because the latter figure is easily understood by patients. We studied the association between blood glucose levels revealed by the oral glucose tolerance test (OGTT) and HbA1c levels in a Korean population. A total of 1,000 subjects aged 30 to 64 years from the Cardiovascular and Metabolic Diseases Etiology Research Center cohort were included. Fasting glucose levels, post-load glucose levels at 30, 60, and 120 minutes into the OGTT, and HbA1c levels were measured. Linear regression of HbA1c with mean blood glucose levels derived using the OGTT revealed a significant correlation between these measures (predicted mean glucose [mg/dL] = 49.4 × HbA1c [%] - 149.6; R (2) = 0.54, p < 0.001). Our linear regression equation was quite different from that of the Alc-Derived Average Glucose (ADAG) study and Diabetes Control and Complications Trial (DCCT) cohort. Discrepancies between our results and those of the ADAG study and DCCT cohort may be attributable to differences in the test methods used and the extent of insulin secretion. More studies are needed to evaluate the association between HbA1c and self monitoring blood glucose levels.

Grave's Eye disease developing following radioiodine treatment for toxic nodular goitre.

PubMed

Tahrani, A A; Rangan, S; Moulik, P

2007-07-01

The development of Grave's ophthalmopathy (GO) following radioiodine (RI) treatment for Grave's thyrotoxicosis, though controversial, is well described. The development of ophthalmopathy following RI treatment for toxic nodular goitre is much less recognised. We report a 49 year-old female patient who developed thyrotoxicosis and GO after receiving RI treatment for toxic nodular goitre and we also review the relevant literature.

A rare case of laryngotracheal chondrosarcoma in a patient with past history of radioiodine therapy for thyroid cancer.

PubMed

Mohajeri, Gholamreza; Hekmatnia, Ali; Ahrar, Hossein; Hekmatnia, Farzane; Nia, Reza Basirat; Afsharmoghadam, Nushin; Eftekhari, Mehdi; Jafarpishe, Saleh

2013-01-01

Tracheal chondrosarcoma is a rare malignant mesenchymal tumor and there are less than 15 reports in the literature. We report a rare case of laryngotracheal chondrosarcoma in a 74-year-old man. He gave a history of radioiodine therapy for thyroid papillary carcinoma about 24 years ago. Diagnostic steps, histological presentation, and therapy are described in detail.

A CuNi/C Nanosheet Array Based on a Metal-Organic Framework Derivate as a Supersensitive Non-Enzymatic Glucose Sensor

NASA Astrophysics Data System (ADS)

Zhang, Li; Ye, Chen; Li, Xu; Ding, Yaru; Liang, Hongbo; Zhao, Guangyu; Wang, Yan

2018-06-01

Bimetal catalysts are good alternatives for non-enzymatic glucose sensors owing to their low cost, high activity, good conductivity, and ease of fabrication. In the present study, a self-supported CuNi/C electrode prepared by electrodepositing Cu nanoparticles on a Ni-based metal-organic framework (MOF) derivate was used as a non-enzymatic glucose sensor. The porous construction and carbon scaffold inherited from the Ni-MOF guarantee good kinetics of the electrode process in electrochemical glucose detection. Furthermore, Cu nanoparticles disturb the array structure of MOF derived films and evidently enhance their electrochemical performances in glucose detection. Electrochemical measurements indicate that the CuNi/C electrode possesses a high sensitivity of 17.12 mA mM-1 cm-2, a low detection limit of 66.67 nM, and a wider linearity range from 0.20 to 2.72 mM. Additionally, the electrode exhibits good reusability, reproducibility, and stability, thereby catering to the practical use of glucose sensors. Similar values of glucose concentrations in human blood serum samples are detected with our electrode and with the method involving glucose-6-phosphate dehydrogenase; the results further demonstrate the practical feasibility of our electrode.

Variation in the use of definitive treatment options in the management of Graves' disease: a UK clinician survey.

PubMed

Hookham, Jessica; Collins, Emma E; Allahabadia, Amit; Balasubramanian, Sabapathy P

2017-04-01

Graves' disease can be treated with antithyroid drugs (ATDs), radioiodine or surgery. Use of definitive treatments (radioiodine or surgery) varies widely across centres. Specific clinical circumstances, local facilities, patient and clinician preferences and perceptions will affect the choice of treatment. Detailed understanding of UK clinicians' views and their rationale for different treatments is lacking. To study the preferences and perceptions of UK clinicians on the role of surgery and radioiodine in the management of Graves' disease. 'British Thyroid Association' (BTA), 'Society for Endocrinology' (SFE) and 'British Association of Endocrine and Thyroid Surgeons' (BAETS) members were invited to complete an online survey examining their management decisions in Graves' disease and factors that influenced their decisions. 158 responses from UK consultants were included. The ratio of physicians to surgeons was 11:5 and males to females was 12:4. Most clinicians would commence ATDs in uncomplicated first presentation of Graves' disease. A wide range of risk estimates on the effectiveness and risks of treatment was given by clinicians. Radioiodine was used most frequently in relapsed Graves' disease. However, severe eye disease and pregnancy strongly influenced choice in favour of surgery. Surgeons underestimated the success of radioiodine (p<0.01) and were more likely to recommend thyroidectomy than physicians. This survey demonstrates significant variation in clinicians' perceptions of risks of treatment and their choice of management options for relapsed Graves' disease. The variation appeared to be dependent on patient and disease-specific factors as well as physician experience, gender and specialty. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Re-induction of cell differentiation and (131)I uptake in dedifferentiated FTC-133 cell line by TSHR gene transfection.

PubMed

Feng, Fang; Wang, Hui; Hou, Shasha; Fu, Hongliang

2012-11-01

Radioiodine therapy is commonly used to treat differentiated thyroid cancer (DTC), but a major challenge is dedifferentiation of DTC with the loss of radioiodine uptake. TSHR is a key molecule regulating thyrocyte proliferation and function. This study aimed to test the therapeutic potential of TSHR in dedifferentiated DTC by gene transfection in order to restore cell differentiation and radioiodine uptake. Dedifferentiated FTC-133 (dFTC-133) cells were obtained by monoclonal culture of FTC-133 cell line after (131)I radiation. Recombinant plasmid pcDNA3.1-hTSHR was transfected into dFTC-133 cells by using Lipofectamine 2000 reagent. Immunofluorescence analysis was carried out to confirm TSHR expression and its location. Radioiodine uptake assay was thereafter investigated. mRNAs and proteins of TSHR and other thyroid differentiated markers were detected by real-time PCR and western blot respectively. Among the thyroid specific genes in dFTC-133 cells with stable low radioiodine uptake, TSHR was down-regulated most significantly compared with FTC-133. Then, after TSHR gene transfection, augmented expression of TSHR was observed in dFTC-133 cell surface and cytoplasm by immunofluorescence analysis. It was found that (125)I uptake was 2.9 times higher (t=28.63, P<.01) in cells with TSHR transfection than control. The mRNAs of TSHR, NIS, TPO and Tg were also significantly increased by 1.7 times (t=13.8, P<.05), 4 times (t=28.52, P<.05), 1.5 times (t=14.43, P<.05) and 2.2 times (t=19.83, P<.05) respectively compared with control group. Decreased TSHR expression correlated with FTC-133 ongoing dedifferentiation. TSHR transfection contributed to the re-differentiation of dedifferentiated thyroid follicular carcinoma cells. Copyright © 2012 Elsevier Inc. All rights reserved.

Childhood thyroid radioiodine exposure and subsequent infertility in the intermountain fallout cohort.

PubMed

Stone, Mary Bishop; Stanford, Joseph B; Lyon, Joseph L; VanDerslice, James A; Alder, Stephen C

2013-01-01

Above-ground and underground nuclear weapon detonation at the Nevada Test Site (1951-1992) has resulted in radioiodine exposure for nearby populations. Although the long-term effect of environmental radioiodine exposure on thyroid disease has been well studied, little is known regarding the effect of childhood radioiodine exposure on subsequent fertility. We investigated early childhood thyroid radiation exposure from nuclear testing fallout (supplied predominantly by radioactive isotopes of iodine) and self-reported lifetime incidence of male or female infertility or sterility. Participants were members of the 1965 Intermountain Fallout Cohort, schoolchildren at the time of exposure who were reexamined during two subsequent study phases to collect dietary and reproductive histories. Thyroid radiation exposure was calculated via an updated dosimetry model. We used multivariable logistic regression with robust sandwich estimators to estimate odds ratios for infertility, adjusted for potential confounders and (in separate models) for a medically confirmed history of thyroid disease. Of 1,389 participants with dosimetry and known fertility history, 274 were classified as infertile, including 30 classified as sterile. Childhood thyroid radiation dose was possibly associated with infertility [adjusted odds ratio (AOR) = 1.17; 95% CI: 0.82, 1.67 and AOR = 1.35; 95% CI: 0.96, 1.90 for the middle and upper tertiles vs. the first tertile of exposure, respectively]. The odds ratios were attenuated (AOR = 1.08; 95% CI: 0.75, 1.55 and AOR = 1.29; 95% CI: 0.91, 1.83 for the middle and upper tertiles, respectively) after adjusting for thyroid disease. There was no association of childhood radiation dose and sterility. Our findings suggest that childhood radioiodine exposure from nuclear testing may be related to subsequent adult infertility. Further research is required to confirm this.

Investigation of factors influencing radioiodine (131I) biokinetics in patients with benign thyroid disease using nonlinear mixed effects approach.

PubMed

Topić Vučenović, Valentina; Rajkovača, Zvezdana; Jelić, Dijana; Stanimirović, Dragi; Vuleta, Goran; Miljković, Branislava; Vučićević, Katarina

2018-05-13

Radioiodine ( 131 I) therapy is the common treatment option for benign thyroid diseases. The objective of this study was to characterize 131 I biokinetics in patients with benign thyroid disease and to investigate and quantify the influence of patients' demographic and clinical characteristics on intra-thyroidal 131 I kinetics by developing a population model. Population pharmacokinetic analysis was performed using a nonlinear mixed effects approach. Data sets of 345 adult patients with benign thyroid disease, retrospectively collected from patients' medical records, were evaluated in the analysis. The two-compartment model of 131 I biokinetics representing the blood compartment and thyroid gland was used as the structural model. Results of the study indicate that the rate constant of the uptake of 131 I into the thyroid (k tu ) is significantly influenced by clinical diagnosis, age, functional thyroid volume, free thyroxine in plasma (fT 4 ), use of anti-thyroid drugs, and time of discontinuation of therapy before administration of the radioiodine (THDT), while the effective half-life of 131 I is affected by the age of the patients. Inclusion of the covariates in the base model resulted in a decrease of the between subject variability for k tu from 91 (3.9) to 53.9 (4.5)%. This is the first population model that accounts for the influence of fT 4 and THDT on radioiodine kinetics. The model could be used for further investigations into the correlation between thyroidal exposure to 131 I and the outcome of radioiodine therapy of benign thyroid disease as well as the development of dosing recommendations.

Effects of skeleton structure on necrosis targeting and clearance properties of radioiodinated dianthrones.

PubMed

Zhang, Dongjian; Jiang, Cuihua; Yang, Shengwei; Gao, Meng; Huang, Dejian; Wang, Xiaoning; Shao, Haibo; Feng, Yuanbo; Sun, Ziping; Ni, Yicheng; Zhang, Jian; Yin, Zhiqi

2016-01-01

Necrosis avid agents (NAAs) can be used for diagnose of necrosis-related diseases, evaluation of therapeutic responses and targeted therapeutics of tumor. In order to probe into the effects of molecular skeleton structure on necrosis targeting and clearance properties of radioiodinated dianthrones, four dianthrone compounds with the same substituents but different skeletal structures, namely Hypericin (Hyp), protohypericin (ProHyp), emodin dianthrone mesomer (ED-1) and emodin dianthrone raceme (ED-2) were synthesized and radioiodinated. Then radioiodinated dianthrones were evaluated in vitro for their necrosis avidity in A549 lung cancer cells untreated and treated with H2O2. Their biodistribution and pharmacokinetic properties were determined in rat models of induced necrosis. In vitro cell assay revealed that destruction of rigid skeleton structure dramatically reduced their necrosis targeting ability. Animal studies demonstrated that destruction of rigid skeleton structure dramatically reduced the necrotic tissue uptake and speed up the clearance from the most normal tissues for the studied compounds. Among these (131)I-dianthrones, (131)I-Hyp exhibited the highest uptake and persistent retention in necrotic tissues. Hepatic infarction could be clearly visualized by SPECT/CT using (131)I-Hyp as an imaging probe. The results suggest that the skeleton structure of Hyp is the lead structure for further structure optimization of this class of NAAs.

Investigation of public exposure resulted from the radioiodine delay tank facility of nuclear medicine department

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yusof, Mohd Fahmi Mohd, E-mail: mfahmi@usm.my; Ali, Abdul Muhaimin Mat; Abdullah, Reduan

The study is carried out to assess the exposure rate that could contribute to public exposure in a radioiodine ward delay tank facility of Radiotherapy, Oncology and Nuclear Medicine, Department, Hospital Universiti Sains Malaysia (HUSM). The exposure rate at several locations including the delay tank room, doorway and at the public walking route was measured using Victoreen 415P-RYR survey meter. The radioactive level of the {sup 131}I waste was measured using Captus 3000 well counting system. The results showed that exposure rate and total count of the delay tank sample increased when the radioiodine ward was fully occupied with patientmore » and reduced when the ward was vacant. Occupancy of radioiodine ward for two consecutive weeks had dramatically increased the exposure rate around the delay tank and radioactive level of {sup 131}I waste. The highest exposure rate and radioactive level was recorded when the ward was occupied for two consecutive weeks with 177.00 µR/h and 58.36 kcpm respectively. The exposure rate decreased 15.76 % when the door of the delay tank room was closed. The exposure rate at public walking route decreased between 15.58 % and 36.92 % as the distance increased between 1 and 3 m.« less

Glucose responsive insulin production from human embryonic germ (EG) cell derivatives.

PubMed

Clark, Gregory O; Yochem, Robert L; Axelman, Joyce; Sheets, Timothy P; Kaczorowski, David J; Shamblott, Michael J

2007-05-11

Type 1 diabetes mellitus subjects millions to a daily burden of disease management, life threatening hypoglycemia and long-term complications such as retinopathy, nephropathy, heart disease, and stroke. Cell transplantation therapies providing a glucose-regulated supply of insulin have been implemented clinically, but are limited by safety, efficacy and supply considerations. Stem cells promise a plentiful and flexible source of cells for transplantation therapies. Here, we show that cells derived from human embryonic germ (EG) cells express markers of definitive endoderm, pancreatic and beta-cell development, glucose sensing, and production of mature insulin. These cells integrate functions necessary for glucose responsive regulation of preproinsulin mRNA and expression of insulin C-peptide in vitro. Following transplantation into mice, cells become insulin and C-peptide immunoreactive and produce plasma C-peptide in response to glucose. These findings suggest that EG cell derivatives may eventually serve as a source of insulin producing cells for the treatment of diabetes.

Simultaneous quantification of endogenous and exogenous plasma glucose by isotope dilution LC-MS/MS with indirect MRM of the derivative tag.

PubMed

Yu, Lingling; Wen, Chao; Li, Xing; Fang, Shiqi; Yang, Lichuan; Wang, Tony; Hu, Kaifeng

2018-03-01

Quantification of endogenous and exogenous plasma glucose can help more comprehensively evaluate the glucose metabolic status. A ratio-based approach using isotope dilution liquid chromatography tandem mass spectrometry (ID LC-MS/MS) with indirect multiple reaction monitoring (MRM) of the derivative tag was developed to simultaneously quantify endo-/exogenous plasma glucose. Using diluted D-[ 13 C 6 ] glucose as tracer of exogenous glucose, 12 C 6 / 13 C 6 glucoses were first derivatized and then data were acquired in MRM mode. The metabolism of exogenous glucose can be tracked and the concentration ratio of endo/exo-genous glucose can be measured by calculating the endo-/exo-genous glucose concentrations from peak area ratio of specific daughter ions. Joint application of selective derivatization and MRM analysis not only improves the sensitivity but also minimizes the interference from the background of plasma, which warrants the accuracy and reproducibility. Good agreement between the theoretical and calculated concentration ratios was obtained with a linear correlation coefficient (R) of 0.9969 in the range of D-glucose from 0.5 to 20.0 mM, which covers the healthy and diabetic physiological scenarios. Satisfactory reproducibility was obtained by evaluation of the intra- and inter-day precisions with relative standard deviations (RSDs) less than 5.16%, and relative recoveries of 85.96 to 95.92% were obtained at low, medium, and high concentration, respectively. The method was successfully applied to simultaneous determination of the endo-/exogenous glucose concentration in plasma of non-diabetic and type II diabetic cynomolgus monkeys. Graphical Abstract The scheme of the proposed ratio-based approach using isotope dilution LC-MS/MS with indirect MRM of the derivative tag for simultaneous quantification of endogenous and exogenous plasma glucose.

Naphthalenemethyl ester derivative of dihydroxyhydrocinnamic acid, a component of cinnamon, increases glucose disposal by enhancing translocation of glucose transporter 4.

PubMed

Kim, W; Khil, L Y; Clark, R; Bok, S H; Kim, E E; Lee, S; Jun, H S; Yoon, J W

2006-10-01

Cinnamon extracts have anti-diabetic effects. Phenolic acids, including hydrocinnamic acids, were identified as major components of cinnamon extracts. Against this background we sought to develop a new anti-diabetic compound using derivatives of hydroxycinnamic acids purified from cinnamon. We purified hydroxycinnamic acids from cinnamon, synthesised a series of derivatives, and screened them for glucose transport activity in vitro. We then selected the compound with the highest glucose transport activity in epididymal adipocytes isolated from male Sprague-Dawley rats in vitro, tested it for glucose-lowering activity in vivo, and studied the mechanisms involved. A naphthalenemethyl ester of 3,4-dihydroxyhydrocinnamic acid (DHH105) showed the highest glucose transport activity in vitro. Treatment of streptozotocin-induced diabetic C57BL/6 mice and spontaneously diabetic ob/ob mice with DHH105 decreased blood glucose levels to near normoglycaemia. Further studies revealed that DHH105 increased the maximum speed of glucose transport and the translocation of glucose transporter 4 (GLUT4, now known as solute carrier family 2 [facilitated glucose transporter], member 4 [SLC2A4]) in adipocytes, resulting in increased glucose uptake. In addition, DHH105 enhanced phosphorylation of the insulin receptor-beta subunit and insulin receptor substrate-1 in adipocytes, both in vitro and in vivo. This resulted in the activation of phosphatidylinositol 3-kinase and Akt/protein kinase B, contributing to the translocation of GLUT4 to the plasma membrane. We conclude that DHH105 lowers blood glucose levels through the enhancement of glucose transport, mediated by an increase in insulin-receptor signalling. DHH105 may be a valuable candidate for a new anti-diabetic drug.

THE RESULTS OF USING RADIOIODINE FOR STUDIES OF THE FUNCTIONAL STATE OF THE THYROID GLAND IN CARDIOVASCULAR AND ALIMENTARY DISEASES (in Russian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kalyuzhnii, I.T.

1962-04-01

The thyroid function in 60 healthy persons and 2000 patients was assessed. An elevated capacity of the thyroid gland to concentrate radioiodine was observed in almost 50% of rheumocarditis patients, one-third of lamblious cholecystitis cases, one-fourth of patients with rheumatic disease of the heart and circulatory insufficiency of the 1st and 2nd degrees, and more rarely in patients with neurosis, peptic ulcer, and hypertensive vascular disease of the 1st stage. Moderately low indexes of radioiodine accumulation in the thyroid gland were found in patients with subacute septic endocarditis, in two-thirds of patients with atherosclerosis and hypertensive vascular disease (2nd andmore » 3rd stages), in half of cases with rheumatic heart disease and circulatory insufficiency of the 3rd degree, as well as in pulmonary heart, chronic gastritis, and ulcerous disease. (auth)« less

Astrocyte glycogen as an emergency fuel under conditions of glucose deprivation or intense neural activity.

PubMed

Brown, Angus M; Ransom, Bruce R

2015-02-01

Energy metabolism in the brain is a complex process that is incompletely understood. Although glucose is agreed as the main energy support of the brain, the role of glucose is not clear, which has led to controversies that can be summarized as follows: the fate of glucose, once it enters the brain is unclear. It is not known the form in which glucose enters the cells (neurons and glia) within the brain, nor the degree of metabolic shuttling of glucose derived metabolites between cells, with a key limitation in our knowledge being the extent of oxidative metabolism, and how increased tissue activity alters this. Glycogen is present within the brain and is derived from glucose. Glycogen is stored in astrocytes and acts to provide short-term delivery of substrates to neural elements, although it may also contribute an important component to astrocyte metabolism. The roles played by glycogen awaits further study, but to date its most important role is in supporting neural elements during increased firing activity, where signaling molecules, proposed to be elevated interstitial K(+), indicative of elevated neural firing rates, activate glycogen phosphorylase leading to increased production of glycogen derived substrate.

The Molecular Effect of Diagnostic Absorbed Doses from 131I on Papillary Thyroid Cancer Cells In Vitro.

PubMed

Stasiołek, Mariusz; Adamczewski, Zbigniew; Śliwka, Przemysław W; Puła, Bartosz; Karwowski, Bolesław; Merecz-Sadowska, Anna; Dedecjus, Marek; Lewiński, Andrzej

2017-06-15

Diagnostic whole-body scan is a standard procedure in patients with thyroid cancer prior to the application of a therapeutic dose of 131 I. Unfortunately, administration of the radioisotope in a diagnostic dose may decrease further radioiodine uptake-the phenomenon called "thyroid stunning". We estimated radiation absorbed dose-dependent changes in genetic material, in particular in the sodium iodide symporter (NIS) gene promoter, and the NIS protein level in a K1 cell line derived from the metastasis of a human papillary thyroid carcinoma exposed to 131 I in culture. The different activities applied were calculated to result in absorbed doses of 5, 10 and 20 Gy. Radioiodine did not affect the expression of the NIS gene at the mRNA level, however, we observed significant changes in the NIS protein level in K1 cells. The decrease of the NIS protein level observed in the cells subjected to the lowest absorbed dose was paralleled by a significant increase in 8-oxo-dG concentrations ( p < 0.01) and followed by late activation of the DNA repair pathways. Our findings suggest that the impact of 131 I radiation on thyroid cells, in the range compared to doses absorbed during diagnostic procedures, is not linear and depends on various factors including the cellular components of thyroid pathology.

Effects of food-deprivation and refeeding on the regulation and sources of blood glucose appearance in European seabass (Dicentrarchus labrax L.).

PubMed

Viegas, Ivan; Rito, João; González, Juan Diego; Jarak, Ivana; Carvalho, Rui A; Metón, Isidoro; Pardal, Miguel A; Baanante, Isabel V; Jones, John G

2013-11-01

Sources of blood glucose in European seabass (initial weight 218.0±43.0g; mean±S.D., n=18) were quantified by supplementing seawater with deuterated water (5%-(2)H2O) for 72h and analyzing blood glucose (2)H-enrichments by (2)H NMR. Three different nutritional states were studied: continuously fed, 21-day of fast and 21-day fast followed by 3days of refeeding. Plasma glucose levels (mM) were 10.7±6.3 (fed), 4.8±1.2 (fasted), and 9.3±1.4 (refed) (means±S.D., n=6), showing poor glycemic control. For all conditions, (2)H-enrichment of glucose position 5 was equivalent to that of position 2 indicating that blood glucose appearance from endogenous glucose 6-phosphate (G6P) was derived by gluconeogenesis. G6P-derived glucose accounted for 65±7% and 44±10% of blood glucose appearance in fed and refed fish, respectively, with the unlabeled fraction assumed to be derived from dietary carbohydrate (35±7% and 56±10%, respectively). For 21-day fasted fish, blood glucose appearance also had significant contributions from unlabeled glucose (52±16%) despite the unavailability of dietary carbohydrates. To assess the role of hepatic enzymes in glycemic control, activity and mRNA levels of hepatic glucokinase (GK) and glucose 6-phosphatase (G6Pase) were assessed. Both G6Pase activity and expression declined with fasting indicating the absence of a classical counter-regulatory stimulation of hepatic glucose production in response to declining glucose levels. GK activities were basal during fed and fasted conditions, but were strongly stimulated by refeeding. Overall, hepatic G6Pase and GK showed limited capacity in regulating glucose levels between feeding and fasting states. © 2013.

Development of Tethered Hsp90 Inhibitors Carrying Radioiodinated Probes to Specifically Discriminate and Kill Malignant Breast Tumor Cells

DTIC Science & Technology

2016-05-01

both active (5) and inactive (12) probes. To obtain a control compound with very similar physical properties but lacking the ability to bind to Hsp90...procedure was developed and then adapted and modified to provide workable protocols for radioiodination. An inactive control molecule was also developed...955-959. 4. Impact. The successful synthesis of both and active and inactive tethered Hsp90 carrying iodine that can be successfully

Effective doses to family members of patients treated with radioiodine-131

NASA Astrophysics Data System (ADS)

Zdraveska Kocovska, M.; Vaskova, O.; Majstorov, V.; Kuzmanovska, S.; Pop Gjorceva, D.; Spasic Jokic, V.

2011-09-01

The purpose of this study was to evaluate the effective dose to family members of thyroid cancer and hyperthyroid patients treated with radioiodine-131, and also to compare the results with dose constraints proposed by the International Commission of Radiological Protection (ICRP) and the Basic Safety Standards (BSS) of the International Atomic Energy Agency (IAEA). For the estimation of the effective doses, sixty family members of sixty patients, treated with radioiodine-131, and thermoluminiscent dosimeters (Model TLD 100) were used. Thyroid cancer patients were hospitalized for three days, while hyperthyroid patients were treated on out-patient basis. The family members wore TLD in front of the torso for seven days. The radiation doses to family members of thyroid cancer patients were well below the recommended dose constraint of 1 mSv. The mean value of effective dose was 0.21 mSv (min 0.02 - max 0.51 mSv). Effective doses, higher than 1 mSv, were detected for 11 family members of hyperthyroid patients. The mean value of effective dose of family members of hyperthyroid patients was 0.87 mSv (min 0.12 - max 6.79). The estimated effective doses to family members of hyperthyroid patients were higher than the effective doses to family members of thyroid carcinoma patients. These findings may be considered when establishing new national guidelines concerning radiation protection and release of patients after a treatment with radioiodine therapy.

Validation of different measures of insulin sensitivity of glucose metabolism in dairy cows using the hyperinsulinemic euglycemic clamp test as the gold standard.

PubMed

De Koster, J; Hostens, M; Hermans, K; Van den Broeck, W; Opsomer, G

2016-10-01

The aim of the present research was to compare different measures of insulin sensitivity in dairy cows at the end of the dry period. To do so, 10 clinically healthy dairy cows with a varying body condition score were selected. By performing hyperinsulinemic euglycemic clamp (HEC) tests, we previously demonstrated a negative association between the insulin sensitivity and insulin responsiveness of glucose metabolism and the body condition score of these animals. In the same animals, other measures of insulin sensitivity were determined and the correlation with the HEC test, which is considered as the gold standard, was calculated. Measures derived from the intravenous glucose tolerance test (IVGTT) are based on the disappearance of glucose after an intravenous glucose bolus. Glucose concentrations during the IVGTT were used to calculate the area under the curve of glucose and the clearance rate of glucose. In addition, glucose and insulin data from the IVGTT were fitted in the minimal model to derive the insulin sensitivity parameter, Si. Based on blood samples taken before the start of the IVGTT, basal concentrations of glucose, insulin, NEFA, and β-hydroxybutyrate were determined and used to calculate surrogate indices for insulin sensitivity, such as the homeostasis model of insulin resistance, the quantitative insulin sensitivity check index, the revised quantitative insulin sensitivity check index and the revised quantitative insulin sensitivity check index including β-hydroxybutyrate. Correlation analysis revealed no association between the results obtained by the HEC test and any of the surrogate indices for insulin sensitivity. For the measures derived from the IVGTT, the area under the curve for the first 60 min of the test and the Si derived from the minimal model demonstrated good correlation with the gold standard. Copyright © 2016 Elsevier Inc. All rights reserved.

Glucose responsive insulin production from human embryonic germ (EG) cell derivatives

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clark, Gregory O.; Yochem, Robert L.; Axelman, Joyce

2007-05-11

Type 1 diabetes mellitus subjects millions to a daily burden of disease management, life threatening hypoglycemia and long-term complications such as retinopathy, nephropathy, heart disease, and stroke. Cell transplantation therapies providing a glucose-regulated supply of insulin have been implemented clinically, but are limited by safety, efficacy and supply considerations. Stem cells promise a plentiful and flexible source of cells for transplantation therapies. Here, we show that cells derived from human embryonic germ (EG) cells express markers of definitive endoderm, pancreatic and {beta}-cell development, glucose sensing, and production of mature insulin. These cells integrate functions necessary for glucose responsive regulation ofmore » preproinsulin mRNA and expression of insulin C-peptide in vitro. Following transplantation into mice, cells become insulin and C-peptide immunoreactive and produce plasma C-peptide in response to glucose. These findings suggest that EG cell derivatives may eventually serve as a source of insulin producing cells for the treatment of diabetes.« less

HBA1C AND MEAN GLUCOSE DERIVED FROM SHORT-TERM CONTINUOUS GLUCOSE MONITORING ASSESSMENT DO NOT CORRELATE IN PATIENTS WITH HBA1C >8.

PubMed

Yamada, Eijiro; Okada, Shuichi; Nakajima, Yasuyo; Bastie, Claire C; Vatish, Manu; Tagaya, Yuko; Osaki, Aya; Shimoda, Yoko; Shibusawa, Ryo; Saito, Tsugumichi; Okamura, Takashi; Ozawa, Atsushi; Yamada, Masanobu

2017-01-01

Optimum therapy for patients with diabetes depends on both acute and long-term changes in plasma glucose, generally assessed by glycated hemoglobin (HbA1c) levels. However, the correlation between HbA1c and circulating glucose has not been fully determined. Therefore, we carefully examined this correlation when glucose levels were assessed by continuous glucose monitoring (CGM). Fifty-one patients (70% female, 30% male) were examined; among them were 28 with type 1 diabetes and 23 with type 2 diabetes. Clinically determined HbA1c levels were compared with blood glucose determined by CGM during a short time period. Changes in HbA1c levels up to 8.0% showed a clear and statistically strong correlation (R = 0.6713; P<.0001) with mean blood glucose levels measured by CGM, similar to that observed in the A1c-derived Average Glucose study in which patients were monitored for a longer period. However, we found no statistical correlation (R = 0.0498; P = .83) between HbA1c and CGM-assessed glucose levels in our patient population when HbA1c was >8.0%. Short-term CGM appears to be a good clinical indicator of long-term glucose control (HbA1c levels); however, cautions should be taken while interpreting CGM data from patients with HbA1c levels >8.0%. Over- or underestimation of the actual mean glucose from CGM data could potentially increase the risks of inappropriate treatment. As such, our results indicate that a more accurate analysis of CGM data might be useful to adequately tailor clinical treatments. ADAG = A1c-Derived Average Glucose CGM = continuous glucose monitoring %CV = percent coefficient of variation HbA1c = glycated hemoglobin.

Five months' follow-up of patients with and without iodine-positive lymph node metastases of thyroid carcinoma as disclosed by (131)I-SPECT/CT at the first radioablation.

PubMed

Schmidt, Daniela; Linke, Rainer; Uder, Michael; Kuwert, Torsten

2010-04-01

In differentiated thyroid carcinoma (DTC), (131)I-SPECT/CT is more accurate in identifying radioiodine-positive lymph node metastases (LNM) than planar whole-body scans (WBS). The purpose of this study was to investigate the value of (131)I-SPECT/CT performed at the first radioablation to predict the occurrence and/or persistence of cervical radioiodine-positive LNM 5 months later. The study included 81 DTC patients that had had SPECT/ spiral CT after radioablation of thyroid remnants after thyroidectomy. The patients were re-examined 5 months later using (131)I-WBS performed at TSH stimulation. In addition, SPECT/CT of the neck was performed in patients with iodine-positive cervical foci to distinguish between thyroid remnant and LNM. The outcome variable of the study was the detection or exclusion of iodine-positive cervical LNM. Of 61 patients without a SPECT/CT diagnosis of (131)I-positive LNM at radioablation, 60 had no (131)I-positive LNM at follow-up. In the remaining patient of this group, a new radioiodine-positive LNM was detected. In 17 of 20 patients with a SPECT/CT diagnosis of (131)I-positive LNM (n = 19) or an indeterminate lesion (n = 1) at first radioablation, no (131)I-positive LNM were detected 5 months later. Radioiodine-positive LNM persisted in three patients of this group. (131)I-SPECT/CT has a high negative predictive value with regard to the occurrence of radioiodine-positive cervical LNM 5 months after initial therapy. The majority of iodine-positive LNM diagnosed by SPECT/CT at radioablation disappear within 5 months. These findings motivate further research into the value of (131)I-SPECT/CT of the neck for predicting recurrence and planning surgical reintervention in DTC.

A NTCP approach for estimating the outcome in radioiodine treatment of hyperthyroidism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Strigari, L.; Sciuto, R.; Benassi, M.

2008-09-15

Radioiodine has been in use for over 60 years as a treatment for hyperthyroidism. Major changes in clinical practice have led to accurate dosimetry capable of avoiding the risks of adverse effects and the optimization of the treatment. The aim of this study was to test the capability of a radiobiological model, based on normal tissue complication probability (NTCP), to predict the outcome after oral therapeutic {sup 131}I administration. Following dosimetric study, 79 patients underwent treatment for hyperthyroidism using radioiodine and then 67 had at least a one-year follow up. The delivered dose was calculated using the MIRD formula, takingmore » into account the measured maximum uptake of administered iodine transferred to the thyroid, U0, and the effective clearance rate, T{sub eff} and target mass. The dose was converted to normalized total dose delivered at 2 Gy per fraction (NTD{sub 2}). Furthermore, the method to take into account the reduction of the mass of the gland during radioiodine therapy was also applied. The clinical outcome and dosimetric parameters were analyzed in order to study the dose-response relationship for hypothyroidism. The TD{sub 50} and m parameters of the NTCP model approach were then estimated using the likelihood method. The TD{sub 50}, expressed as NTD{sub 2}, resulted in 60 Gy (95% C.I.: 45-75 Gy) and 96 Gy (95% C.I.: 86-109 Gy) for patients affected by Graves or autonomous/multinodular disease, respectively. This supports the clinical evidence that Graves' disease should be characterized by more radiosensitive cells compared to autonomous nodules. The m parameter for all patients was 0.27 (95% C.I.: 0.22-0.36). These parameters were compared with those reported in the literature for hypothyroidism induced after external beam radiotherapy. The NTCP model correctly predicted the clinical outcome after the therapeutic administration of radioiodine in our series.« less

Radioiodine therapy in Graves' disease based on tissue-absorbed dose calculations: effect of pre-treatment thyroid volume on clinical outcome.

PubMed

Reinhardt, Michael J; Brink, Ingo; Joe, Alexius Y; Von Mallek, Dirk; Ezziddin, Samer; Palmedo, Holger; Krause, Thomas M

2002-09-01

This study was performed with three aims. The first was to analyse the effectiveness of radioiodine therapy in Graves' disease patients with and without goitres under conditions of mild iodine deficiency using several tissue-absorbed doses. The second aim was to detect further parameters which might be predictive for treatment outcome. Finally, we wished to determine the deviation of the therapeutically achieved dose from that intended. Activities of 185-2,220 MBq radioiodine were calculated by means of Marinelli's formula to deliver doses of 150, 200 or 300 Gy to the thyroids of 224 patients with Graves' disease and goitres up to 130 ml in volume. Control of hyperthyroidism, change in thyroid volume and thyrotropin-receptor antibodies were evaluated 15+/-9 months after treatment for each dose. The results were further evaluated with respect to pre-treatment parameters which might be predictive for therapy outcome. Thyroidal radioiodine uptake was measured every day during therapy to determine the therapeutically achieved target dose and its coefficient of variation. There was a significant dose dependency in therapeutic outcome: frequency of hypothyroidism increased from 27.4% after 150 Gy to 67.7% after 300 Gy, while the frequency of persistent hyperthyroidism decreased from 27.4% after 150 Gy to 8.1% after 300 Gy. Patients who became hypothyroid had a maximum thyroid volume of 42 ml and received a target dose of 256+/-80 Gy. The coefficient of variation for the achieved target dose ranged between 27.7% for 150 Gy and 17.8% for 300 Gy. When analysing further factors which might influence therapeutic outcome, only pre-treatment thyroid volume showed a significant relationship to the result of treatment. It is concluded that a target dose of 250 Gy is essential to achieve hypothyroidism within 1 year after radioiodine therapy in Graves' disease patients with goitres up to 40 ml in volume. Patients with larger goitres might need higher doses.

Extending the Scope of GTFR Glucosylation Reactions with Tosylated Substrates for Rare Sugars Synthesis.

PubMed

Görl, Julian; Possiel, Christian; Sotriffer, Christoph; Seibel, Jürgen

2017-10-18

Functionalized rare sugars were synthesized with 2-, 3-, and 6-tosylated glucose derivatives as acceptor substrates by transglucosylation with sucrose and the glucansucrase GTFR from Streptococcus oralis. The 2- and 3-tosylated glucose derivatives yielded the corresponding 1,6-linked disaccharides (isomaltose analogues), whereas the 6-tosylated glucose derivatives resulted in 1,3-linked disaccharides (nigerose analogue) with high regioselectivity in up to 95 % yield. Docking studies provided insight into the binding mode of the acceptors and suggested two different orientations that were responsible for the change in regioselectivity. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Instantaneous radioiodination of rose bengal at room temperature and a cold-kit therefor. [DOE patent application

DOEpatents

O'Brien, H. Jr.; Hupf, H.B.; Wanek, P.M.

The disclosure relates to the radioiodination of rose bengal at room temperature and a cold-kit therefor. A purified rose bengal tablet is stirred into acidified ethanol at or near room temperature, until a suspension forms. Reductant-free /sup 125/I/sup -/ is added and the resulting mixture stands until the exchange label reaction occurs at room temperature. A solution of sterile isotonic phosphate buffer and sodium hydroxide is added and the final resulting mixture is sterilized by filtration.

ABSORPTION OF I$sup 131$ BY THYROID GLAND IN ATHLETES DURING PHYSICAL EXERTION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khorol, I.S.

Radioiodine absorption by the thyroid gland after prolonged physical exercise (3000 m race) was studied in 16 athletes, aged 20 to 24 years. Two hours after administration of the isotope the level of its accumulation in the gland was halved. In 24 and 72 hours the content of radioiodine in the gland was higher than in experimental conditions without physical exercise. The phenomenon described evidently reflects the normal reaction of the thyroid gland of athletes to habitual physical exercise. (auth)

Development of Tethered Hsp90 Inhibitors Carrying Radioiodinated Probes to Specifically Discriminate and Kill Malignant Breast Tumor Cells

DTIC Science & Technology

2017-05-01

REPORT DATE : May 2017 TYPE OF REPORT: Annual PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012...currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE May 2017 2. REPORT TYPE Annual 3. DATES ... methods developed for stannylation of the molecule such that it can be effectively radioiodinated with either 131I or 124I. Two paths of synthesis

Instantaneous radioiodination of rose bengal at room temperature and a cold kit therefor

DOEpatents

O'Brien, Jr., Harold A.; Hupf, Homer B.; Wanek, Philip M.

1981-01-01

The disclosure relates to the radioiodination of rose bengal at room temperature and a cold-kit therefor. A purified rose bengal tablet is stirred into acidified ethanol at or near room temperature, until a suspension forms. Reductant-free .sup.125 I.sup.- is added and the resulting mixture stands until the exchange label reaction occurs at room temperature. A solution of sterile isotonic phosphate buffer and sodium hydroxide is added and the final resulting mixture is sterilized by filtration.

Sophorolipid-derived unsaturated and epoxy fatty acid estolides as plasticizers for poly(3-hydroxybutyrate)

USDA-ARS?s Scientific Manuscript database

Unsaturated and epoxy fatty acid estolides were synthesized from the omega and omega-1 hydroxy fatty acids derived from sophorolipids (SLs) prepared by fermentation from glucose:soybean oil and glucose:oleic acid, respectively. These estolides were utilized as additives in solution-cast poly(3-hydro...

Metabolic comparison of radiolabeled aniline- and phenol-phthaleins with (131)I.

PubMed

Avcibaşi, Uğur; Avcibaşi, Nesibe; Unak, Turan; Unak, Perihan; Müftüler, Fazilet Zümrüt; Yildirim, Yeliz; Dinçalp, Haluk; Gümüşer, Fikriye Gül; Dursun, Ebru Rükşen

2008-05-01

The metabolic comparison of aniline- and phenol-phthaleins radiolabeled with (131)I ((131)I-APH and (131)I-PPH, respectively) has been investigated in this study. To compare the metabolic behavior of these phthaleins and their glucuronide conjugates radiolabeled with (131)I, scintigraphic and biodistributional techniques were applied using male Albino rabbits. The results obtained have shown that these compounds were successfully radioiodinated with a radioiodination yield of about 100%. Maximum uptakes of (131)I-APH and (131)I-PPH, which were metabolized as N- and O-glucuronides, were observed within 2 h in the bladder and in the small intestine, respectively. In the case of verification of considerably up taking of these compounds also by tumors developed in the small intestine and in the bladder tissues, these results can be expected to be encouraging to test these compounds, which will be radiolabeled with other radioiodines such as (125)I, (123)I and (124)I as imaging and therapeutic agents in nuclear medical applications.

Long-term follow-up in toxic solitary autonomous thyroid nodules treated with radioactive iodine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huysmans, D.A.; Corstens, F.H.; Kloppenborg, P.W.

1991-01-01

The long-term effects of radioiodine treatment on thyroid function in patients with a toxic solitary autonomous thyroid nodule were evaluated. Fifty-two patients received a therapeutic dose of 20 mCi of iodine-131 ({sup 131}I). Duration of follow-up was 10 +/- 4 yr. Follow-up data included a biochemical evaluation of thyroid function. The failure rate (recurrent hyperthyroidism) was 2%. The incidence of hypothyroidism was 6% and was not related to the dose per gram of nodular tissue. Oral administration of 20 mCi of radioiodine is a simple and highly effective method for the treatment of patients with a toxic autonomous thyroid nodule.more » The risk of development of hypothyroidism is low if extranodular uptake of {sup 131}I is prevented. This can be achieved by not treating euthyroid patients, by no longer using injections of exogenous thyroid stimulating hormone in the diagnostic work-up of the patients and by always performing radioiodine imaging shortly before treatment.« less

Prevention of Graves' ophthalmopathy.

PubMed

Bartalena, Luigi

2012-06-01

Smoking is the most important risk factor for the occurrence/progression of Graves' ophthalmopathy (GO), as well as for its lower/slower response to immunosuppression. Accordingly, refrain from smoking should be urged, both as primary prevention (removal of risk factors in Graves' patients without GO), secondary prevention (early detection and treatment of asymptomatic/very mild GO) and tertiary prevention (reduction of complications/disability of overt GO). A 6-month course of 200 μg/day sodium selenite can prevent progression of mild GO to more severe GO and is, therefore, a form of secondary prevention and, probably, primary prevention. Correction of thyroid dysfunction and stable maintenance of euthyroidism are important preventive measures. The optimal treatment for hyperthyroidism in patients with GO is uncertain, because evidence demonstrating the superiority of antithyroid drugs over thyroid ablation (radioiodine, thyroidectomy, or both) is lacking. If radioiodine is used, low-dose steroid prophylaxis is recommended, particularly in smokers, to prevent radioiodine-associated GO progression. Copyright © 2011 Elsevier Ltd. All rights reserved.

Lactoperoxidase catalyzed radioiodination of cell surface immunoglobulin: incorporated radioactivity may not reflect relative cell surface Ig density. [/sup 125/I

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilder, R.L.; Yuen, C.C.; Mage, R.G.

1979-02-01

Rabbit and mouse splenic lymphocytes were radioiodinated by the lactoperoxidase technique, extracted with non-ionic detergent, immunoprecipitated with high titered rabbit anti-kappa antisera, and compared by SDS-PAGE. Mouse sIg peaks were reproducibly larger in size than rabbit sIg peaks (often greater than 10 times). Neither differences in incorporation of label into the rabbit cell surface, nor differences in average sIg density explain this result. Total TCA-precipitable radioactivity was similar in each species. Estimation of the relative amounts of sIg in the mouse and rabbit showed similar average sIg densities. Differences in detergent solubility, proteolytic lability, or antisera used also do notmore » adequately account for this difference. Thus, these data indicate that radioactivity incorporated after lactoperoxidase catalyzed cell surface radioiodination may not reflect cell surface Ig density. Conclusions about cell surface density based upon relative incorporation of radioactivity should be confirmed by other approaches.« less

Giving radioiodine? Think about airport security alarms.

PubMed

Kaniuka-Jakubowska, S; Lewczuk, A; Mizan-Gross, K; Obołończyk, L; Lass, P; Sworczak, K

2012-01-01

An increased sensitivity of airport detectors, a growing number of isotopic tests, and globalization of the society have raised a number of false positive radioactive alarms at airports and public places. This paper presents two new cases of patients who triggered airport security alarms after receiving 740MBq of (131)I for non-toxic goitre and attempts to compare surprisingly limited literature concerning this problem. A 57-year-old man triggered a security alarm at three different airports on the 17th, 28th, and 31st day after radioiodine exposure. Interestingly enough, in the meantime, on the 18th and 22nd day, no radiation was detected in him at the airport where he was twice detained as a source of radiation later on. The second case presents a 45-year-old woman who activated security alarm detectors while crossing a border on her coach trip 28 days after radioiodine administration. Copyright © 2011 Elsevier España, S.L. and SEMNIM. All rights reserved.

Distribution of iodine into blood components of the Sprague-Dawley rat differs with the chemical form administered

NASA Technical Reports Server (NTRS)

Thrall, K. D.; Bull, R. J.; Sauer, R. L.

1992-01-01

It has been reported previously that radioactivity derived from iodine distributes differently in the Sprague-Dawley rat depending on the chemical form administered (Thrall and Bull, 1990). In the present communication we report the differential distribution of radioactivity derived from iodine (I2) and iodide (I-) into blood components. Twice as much radioiodine is in the form of I- in the plasma of animals treated with 125I- compared to 125I2-treated rats. No I2 could be detected in the plasma. With an increase in dose, increasing amounts of radioactivity derived from 125I2-treated animals distribute to whole blood compared to equivalent doses of 125I-, reaching a maxima at a dose of 15.8 mumol I/kg body weight. Most of the radioactivity derived from I2 associates with serum proteins and lipids, in particular with albumin and cholesteryl iodide. These data indicate a differential distribution of radioactivity depending on whether it is administered as iodide or iodine. This is inconsistent with the commonly held view that iodine (I2) is reduced to iodide (I-) before it is absorbed systemically from the gastrointestinal tract.

Para-hydrogenated glucose derivatives as potential 13C-hyperpolarized probes for magnetic resonance imaging.

PubMed

Reineri, Francesca; Santelia, Daniela; Viale, Alessandra; Cerutti, Erika; Poggi, Luisa; Tichy, Tomas; Premkumar, Samuel S D; Gobetto, Roberto; Aime, Silvio

2010-05-26

A set of molecules in which a glucose moiety is bound to a hydrogenable synthon has been synthesized and evaluated for hydrogenation reactions and for the corresponding para-hydrogen-induced polarization (PHIP) effects, in order to select suitable candidates for an in vivo magnetic resonance imaging (MRI) method for the assessment of glucose cellular uptake. It has been found that amidic derivatives do not yield any polarization enhancement, probably due to singlet-triplet state mixing along the reaction pathway. In contrast, ester derivatives are hydrogenated in high yield and afford enhanced (1)H and (13)C NMR spectra after para-hydrogenation. The obtained PHIP patterns are discussed and explained on the basis of the calculated spin level populations in the para-hydrogenated products. These molecules may find interesting applications in (13)C MRI as hyperpolarized probes for assessing the activity of glucose transporters in cells.

Iodine-131 Therapy and Nasolacrimal Duct Obstructions: What We Know and What We Need to Know.

PubMed

Ali, Mohammad Javed

2016-01-01

The aims of the current review are to summarize the etiopathogenesis, symptomatology, management, complications, and outcomes of iodine-131-induced nasolacrimal duct obstructions, to propose a screening protocol and elucidate the potential avenues of future research. The authors performed an electronic database (PubMed, MEDLINE, EMBASE, and Cochrane Library) search of all articles published in English on nasolacrimal duct obstructions following radioiodine therapy. These articles were reviewed along with their relevant cross references. Data reviewed included demographics, presentations, investigations, management, complications, and outcomes. In addition, based on relevant unanswered questions and current lacunae in literature, potential avenues for further research have been elucidated. The frequency of nasolacrimal duct obstruction is reported to range from 2.2% to 18% following I-131 therapy. They are mostly bilateral and noted in patients who receive more than 150 mCi radioiodine. Exact etiopathogenesis is unknown but radiotoxicity to lacrimal sac and nasolacrimal duct is believed to be mediated through a sodium-iodine symporter protein. Although uncommon, it is important to increase awareness among treating physicians and patients receiving radioiodine therapy about the potential side effect of nasolacrimal duct obstruction. Imaging modalities are useful adjuncts in the diagnosis. Dacryocystorhinostomy is the most common modality of management with good outcomes. Nasolacrimal duct obstruction following radioiodine treatment is a distinct clinical entity. Increased awareness would facilitate timely diagnosis, management, and an enhanced quality of life for the patients.

Cost-effectiveness of using recombinant human thyroid-stimulating hormone before radioiodine ablation for thyroid cancer treatment in Spanish hospitals.

PubMed

Vallejo, J A; Muros, M A

In thyroid cancer treatment, the thyroid-stimulating hormone (TSH) must be elevated before radioiodine ablation, either by exogenous (with recombinant human thyrotropin [rhTSH]) or endogenous stimulation by thyroid hormone withdrawal (THW). The use of rhTSH avoids hypothyroidism and favours the subsequent elimination of radioiodine, but involves the cost of the product. For this reason, a cost-effectiveness analysis was performed, taking into account all costs involved and the benefits associated with the use of this therapy. Using a Markov modelling with two analysis arms (rhTSH and THW), stratified into high (100mCi/3700 MBq) and low (30mCi/1110 MBq) radioiodine doses, and using 17 weekly cycles, the incremental cost per quality-adjusted life-year (QALY) related to the use of rhTSH was determined. The clinical inputs included in the model were based on published studies and in a treatment survey conducted in Spain. Radioablation preparation with rhTSH is superior to THW, showing additional benefits (0.048 AVAC), as well as cost savings (-€614.16), with an incremental cost-effectiveness rate (ICER) of -€12,795/QALY. The univariate and multivariate sensitivity analyses showed the result to be robust. The use of rhTSH previous to radioablation in Spain has cost savings, as well as a series of health benefits for the patient, making it highly cost-effective. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Effects of glucose concentration on osteogenic differentiation of type II diabetes mellitus rat bone marrow-derived mesenchymal stromal cells on a nano-scale modified titanium.

PubMed

Yamawaki, I; Taguchi, Y; Komasa, S; Tanaka, A; Umeda, M

2017-08-01

Diabetes mellitus (DM) is a common disease worldwide. Patients with DM have an increased risk of losing their teeth compared with other individuals. Dental implants are a standard of care for treating partial or full edentulism, and various implant surface treatments have recently been developed to increase dental implant stability. However, some studies have reported that DM reduces osseointegration and the success rate of dental implants. The purpose of this study was to determine the effects of high glucose levels for hard tissue formation on a nano-scale modified titanium surface. Titanium disks were heated at 600°C for 1 h after treatment with or without 10 m NaOH solution. All disks were incubated with type II DM rat bone marrow-derived mesenchymal stromal cells before exposure to one of four concentrations of glucose (5.5, 8.0, 12.0 or 24.0 mm). The effect of different glucose concentrations on bone marrow-derived mesenchymal stromal cell osteogenesis and inflammatory cytokines on the nano-scale modified titanium surface was evaluated. Alkaline phosphatase activity decreased with increasing glucose concentration. In contrast, osteocalcin production and calcium deposition were significantly decreased at 8.0 mm glucose, but increased with glucose concentrations over 8.0 mm. Differences in calcium/phosphate ratio associated with the various glucose concentrations were similar to osteocalcin production and calcium deposition. Inflammatory cytokines were expressed at high glucose concentrations, but the nano-scale modified titanium surface inhibited the effect of high glucose concentrations. High glucose concentration increased hard tissue formation, but the quality of the mineralized tissue decreased. Furthermore, the nano-scale modified titanium surface increased mineralized tissue formation and anti-inflammation, but the quality of hard tissue was dependent on glucose concentration. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

NADPH Oxidase versus Mitochondria-Derived ROS in Glucose-Induced Apoptosis of Pericytes in Early Diabetic Retinopathy

PubMed Central

Mustapha, Nik M.; Tarr, Joanna M.; Kohner, Eva M.; Chibber, Rakesh

2010-01-01

Objectives. Using apocynin (inhibitor of NADPH oxidase), and Mitoquinol 10 nitrate (MitoQ; mitochondrial-targeted antioxidant), we addressed the importance of mitochondria versus NADPH oxidase-derived ROS in glucose-induced apoptosis of pericytes. Methods. NADPH oxidase was localised using Western blot analysis and cytochrome C reduction assay. Apoptosis was detected by measuring caspase-3 activity. Intracellular glucose concentration, ROS formation and Nε-(carboxymethyl) lysine (CML) content were measured using Amplex Red assay kit, dihydroethidium (DHE), and competitive immunoabsorbant enzyme-linked assay (ELISA), respectively. Results. NADPH oxidase was localised in the cytoplasm of pericytes suggesting ROS production within intracellular compartments. High glucose (25 mM) significantly increased apoptosis, intracellular glucose concentration, and CML content. Apoptosis was associated with increased gp91phox expression, activity of NADPH oxidase, and intracellular ROS production. Apocynin and not MitoQ significantly blunted the generation of ROS, formation of intracellular CML and apoptosis. Conclusions. NADPH oxidase and not mitochondria-derived ROS is responsible for the accelerated apoptosis of pericytes in diabetic retinopathy. PMID:20652059

DOE Office of Scientific and Technical Information (OSTI.GOV)

Howard, A.D.

The aim of this research was to purify and characterize active opioid receptors and elucidate molecular aspects of opioid receptor heterogeneity. Purification to apparent homogeneity of an opioid binding protein from bovine caudate was achieved by solubilization in the non-ionic detergent, digitonin, followed by sequential chromatography on the opiate affinity matrix, ..beta..-naltrexylethylenediamine-CH-Sepharose 4B, and on the lectine affinity matrix, wheat germ agglutinin-agarose. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE) followed by autoradiography revealed that radioiodinated purified receptor gave a single band. Purified receptor preparations showed a specific activity of 12,000-15,000 fmol of opiate bound per mgmore » of protein. Radioiodinated human beta-endorphin (/sup 125/I-beta-end/sub H/) was used as a probe to investigate the ligand binding subunits of mu and delta opioid receptors. /sup 125/I-beta-end/sub H/ was shown to bind to a variety of opioid receptor-containing tissues with high affinity and specificity with preference for mu and delta sites, and with little, if any, binding to kappa sites. Affinity crosslinking techniques were employed to covalently link /sup 125/I-beta-end/sub H/ to opioid receptors, utilizing derivatives of bis-succinimidyl esters that are bifunctional crosslinkers with specificities for amino and sulfhydryl groups. This, and competition experiments with high type-selective ligands, permitted the assignment of two labeled peptides to their receptor types, namely a peptide of M/sub r/ = 65,000 for mu receptors and one of M/sub r/ = 53,000 for delta receptors.« less

1-/sup 11/C-2-deoxy-D-glucose and process for the preparation thereof

DOEpatents

MacGregor, R.R.; Wolf, A.P.; Shiue, C.Y.; Wan, C.N.

1980-02-08

The novel labelled compound 1-/sup 11/C-2-deoxy-D-glucose, and a process for its preparation from 2,3:4,5-di-O-isopropylidene-D-arabinitol derivatives of relatively high reactivity are disclosed. 1-/sup 11/C-2-deoxy-D-glucose is useful for measuring regional brain glucose metabolism in vivo.

A fluorescent radioiodinated oligonucleotidic photoaffinity probe for protein labeling: synthesis and photolabeling of thrombin.

PubMed

Berens, C; Courtoy, P J; Sonveaux, E

1999-01-01

To study the interactions between oligonucleotides and proteins, an original photoaffinity radiolabeling probe has been synthesized. Starting with a 5'-pyridyldithio-3'-amino-oligonucleotide, the photophore benzophenone was first coupled to the 3' end, through acylation by an activated ester of benzoylbenzoic acid. A fluorescein molecule was grafted by alkylation of the free 5'-SH. This compound was finally radiolabeled with 125I using IodoBeads. The selective photolabeling of thrombin in a complex protein mixture by the radioiodinated probe validates this strategy to identify oligonucleotide-binding proteins.

Usefulness of 68Ga-DOTA-RGD (αvβ3) PET/CT Imaging in Thyroglobulin Elevation With Negative Iodine Scintigraphy.

PubMed

Vatsa, Rakhee; Shykla, Jaya; Mittal, Bhagwant Rai; Bhusari, Priya; Sood, Apurva; Basher, Rajender Kumar; Bhattacharya, Anish

2017-06-01

TENIS (thyroglobulin elevation with negative iodine scintigraphy) syndrome in patients with differentiated thyroid carcinoma is not a rare finding. In such patients, F-FDG PET/CT can help in disease evaluation. RGD tripeptide, used for imaging angiogenesis, may also help in disease detection in patients with negative radioiodine whole-body scan. We present 1 such case in whom Ga-RGD tripeptide imaging was helpful in disease detection in the setting of negative radioiodine whole-body scan.

Structural analysis of fungus-derived FAD glucose dehydrogenase

PubMed Central

Yoshida, Hiromi; Sakai, Genki; Mori, Kazushige; Kojima, Katsuhiro; Kamitori, Shigehiro; Sode, Koji

2015-01-01

We report the first three-dimensional structure of fungus-derived glucose dehydrogenase using flavin adenine dinucleotide (FAD) as the cofactor. This is currently the most advanced and popular enzyme used in glucose sensor strips manufactured for glycemic control by diabetic patients. We prepared recombinant nonglycosylated FAD-dependent glucose dehydrogenase (FADGDH) derived from Aspergillus flavus (AfGDH) and obtained the X-ray structures of the binary complex of enzyme and reduced FAD at a resolution of 1.78 Å and the ternary complex with reduced FAD and D-glucono-1,5-lactone (LGC) at a resolution of 1.57 Å. The overall structure is similar to that of fungal glucose oxidases (GOxs) reported till date. The ternary complex with reduced FAD and LGC revealed the residues recognizing the substrate. His505 and His548 were subjected for site-directed mutagenesis studies, and these two residues were revealed to form the catalytic pair, as those conserved in GOxs. The absence of residues that recognize the sixth hydroxyl group of the glucose of AfGDH, and the presence of significant cavity around the active site may account for this enzyme activity toward xylose. The structural information will contribute to the further engineering of FADGDH for use in more reliable and economical biosensing technology for diabetes management. PMID:26311535

Neutrophilic leukocyte membrane proteins. I. Isolation.

PubMed

Hawkins, D; Sauvé, M

1978-03-01

Rabbit exudate-derived PMN were homogenized and the cell membranes isolated on a two-phase aqueous system. Glycoproteins were extracted from cell membranes with lithium diiodosalicylate. SDS polyacrylamide gel electrophoretic analysis showed a consistent pattern of three major glycoprotein entities. Cells radioiodinated supravitally showed most of the radioactivity associated with larger glycoprotein entities whereas PMN membranes radiolabeled after isolation yielded a single major peak of radioactivity associated with a much smaller protein entity. Heterologous antisera against rabbit PMN, PMN membranes, and membrane glycoproteins were all cytotoxic for PMN in the presence of complement, and all bound to the PMN surface as demonstrated with immunocolloidal gold on electron microscopy. The data suggest that one or more glycoprotein entities are membrane-associated ectoglycoproteins which can be radiolabeled supravitally.

Surface labeling of Pneumocystis carinii from in vitro culture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Radding, J.A.; Armstrong, M.Y.; Bogucki, M.S.

1989-01-01

Pneumocystis carinii is an opportunistic pathogen of man, carried as a commensal in healthy subjects. It frequently causes a fatal pneumonia in the immunosuppressed host. It is a major complication of HIV-1 infection in man (AIDS). Using surface radioiodination of rat-derived P. carinii trophozoites obtained from in vitro culture, a major surface glycoprotein (gp120) has been identified. The glycoprotein exhibits adherent behavior similar to that of the intact organism. Purification of gp120 by conventional methods was unsuccessful as the glycoprotein irreversibly bound to numerous column matrices. A combination of gel chromatography and hydroxyapatite chromatography in sodium dodecylsulfate was utilized tomore » purify the glycoprotein. Some preliminary characterization of the glycoprotein is presented.« less

Uninhibited thyroidal uptake of radioiodine despite iodine excess in amiodarone-induced hypothyroidism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wiersinga, W.M.; Touber, J.L.; Trip, M.D.

1986-08-01

Iodine excess is associated with a low thyroidal radioiodine uptake due to dilution of the radioisotope by the increased stable iodide pool. We studied thyroidal uptake of radioisotopes in cardiac patients with iodine excess due to amiodarone treatment. /sup 99m/Tc-pertechnetate scintigraphy was performed in 13 patients receiving long term amiodarone therapy. Five patients had a clearly visible thyroid gland, and 8 patients had no or a very faint thyroid image. All patients with positive scans had an increased plasma TSH level, whereas all patients with negative scans had a normal or absent TSH response to TRH. Thyroidal uptake and dischargemore » of 123I were studied in 30 other patients. Group I (n = 11) had normal plasma TSH responses to TRH and no iodine excess, group II (n = 7) had normal TSH responses to TRH and excess iodine from metrizoate angiography in the previous month, group III (n = 7) had normal or decreased TSH responses to TRH while receiving long term amiodarone therapy, and group IV (n = 5) had increased TSH responses to TRH while receiving long term amiodarone therapy. The mean radioiodine uptake value in group I (5.4 +/- 0.8% (+/- SE) at 60 min) was higher than those in group II (2.3 +/- 0.7%; P = 0.009) and group III (0.8 +/- 0.3%; P = 0.0005), but not different from that in group IV (5.3 +/- 1.2%; P = NS). Radioiodine discharge after perchlorate (expressed as a percentage of the 60 min uptake) in group I (10.1 +/- 2.2%) was lower than those in group II (24.9 +/- 10.6%; P = 0.05) and group III (28.8 +/- 5.3%; P less than 0.005), whereas discharge in group IV (58.0 +/- 6.1%) was greater than those in group II (P less than 0.05) and group III (P less than 0.01). In conclusion, 1) thyroid visualization by /sup 99m/Tc-pertechnetate and thyroid radioiodine uptake during iodine excess are decreased in euthyroid and hyperthyroid patients, but preserved in hypothyroid patients.« less

Radioiodine treatment of hyperthyroidism in a pregnant women.

PubMed

Berg, G E; Nyström, E H; Jacobsson, L; Lindberg, S; Lindstedt, R G; Mattsson, S; Niklasson, C A; Norén, A H; Westphal, O G

1998-02-01

We describe the effects of radioiodine treatment of a pregnant thyrotoxic woman. The woman received 500 MBq of (131)I in her 20th gestational week. The pregnancy was discovered 10 days after radioiodine administration. A gamma camera examination of the abdomen at that time showed a distinct focus of activity, which was interpreted as the fetal thyroid. Gamma camera examinations of the mother and fetus were performed at 10, 11, 12, 13 and 18 days after administration of the therapeutic activity and were the basis of dose calculations. The child was examined by hormone tests and mental performance tests, up to 8 yr after birth. The uptake at 24 hr postadministration was calculated to be 10 MBq (2%) in the fetal thyroid gland. The effective half-life was 2.5 days, giving a calculated absorbed dose to the fetal thyroid gland of 600 Gy, which is considered to be an ablative dose. The calculated absorbed dose to the fetal body, including brain, was about 100 mGy, and 40 mGy to the fetal gonads. Doses were estimated taking contributions from radioiodine in the mother, the fetal body and the fetal thyroid into consideration. The woman was encouraged to continue her pregnancy and received levothyroxine in a dose to render her slightly thyrotoxic. At full term, an apparently healthy boy, having markedly raised cord blood serum thyroid-stimulating hormone concentration and subnormal thyroxine (T4) and low-normal triiodothyronine (T3) concentrations, was born. Treatment with thyroxine was initiated from the age of 14 days, when the somatosensoric evoked potential latency time increased to a pathological value and hormonal laboratory tests repeatedly confirmed the hypothyroid state. At 8 yr of age, the child attends regular school. A neuropsychological pediatric examination showed that the mental performance was within normal limits, but with an uneven profile. He has a low attention score and displays evidently subnormal capacity regarding figurative memory. Radioiodine treatment in pregnancy in the 20th gestational week does not give a total absorbed dose to the fetal body that justifies termination of pregnancy. A high absorbed dose to the fetal thyroid, however, should be the basis of the management of the pregnancy and offspring.

Food safety regulations: what we learned from the Fukushima nuclear accident.

PubMed

Hamada, Nobuyuki; Ogino, Haruyuki

2012-09-01

On 11 March 2011, the magnitude-9.0 earthquake and a substantial tsunami struck off the northeast coast of Japan. The Fukushima nuclear power plants were inundated and stricken, followed by radionuclide releases outside the crippled reactors. Provisional regulation values for radioactivity in food and drink were set on 17 March and were adopted from the preset index values, except that for radioiodines in water and milk ingested by infants. For radiocesiums, uranium, plutonium and transuranic α emitters, index values were defined in all food and drink not to exceed a committed effective dose of 5 mSv/year. Index values for radioiodines were defined not to exceed a committed equivalent dose to the thyroid of 50 mSv/year, and set in water, milk and some vegetables, but not in other foodstuffs. Index values were calculated as radioactive concentrations of indicator radionuclides ((131)I for radioiodines, (134)Cs and (137)Cs for radiocesiums) by postulating the relative radioactive concentration of coexisting radionuclides (e.g., (132)I, (133)I, (134)I, (135)I and (132)Te for (131)I). Surveys were thence conducted to monitor levels of (131)I, (134)Cs and (137)Cs. Provisional regulation values were exceeded in tap water, raw milk and some vegetables, and restrictions on distribution and consumption began on 21 March. Fish contaminated with radioiodines at levels of concern were then detected, so that the provisional regulation value for radioiodines in seafood adopted from that in vegetables were additionally set on 5 April. Overall, restrictions started within 25 days after the first excess in each food or drink item, and maximum levels were detected in leafy vegetables (54,100 Bq/kg for (131)I, and a total of 82,000 Bq/kg for (134)Cs and (137)Cs). This paper focuses on the logic behind such food safety regulations, and discusses its underlying issues. The outlines of the food monitoring results for 24,685 samples and the enforced restrictions will also be described. Copyright © 2011 Elsevier Ltd. All rights reserved.

Wheat bran biorefinery: an investigation on the starch derived glucose extraction accompanied by pre- and post-treatment steps.

PubMed

Tirpanalan, Özge; Reisinger, Michael; Huber, Florian; Kneifel, Wolfgang; Novalin, Senad

2014-07-01

Wheat bran, a side product of the milling industry, can be considered as a feedstock for biorefineries. Unlike other lignocellulosic feedstock, wheat bran contains a reasonable amount of starch, which is not of recalcitrant nature. Therefore, it can be extracted without a costly pretreatment process. The present work evaluates the extraction of starch derived glucose in relation to a wheat bran biorefinery. The purity of free glucose extracted quantitatively was 44%. The extract was concentrated by threefold via nanofiltration, thereby reaching a glucose concentration of 49 g/L. Hydrothermal treatment (180°C - 20 min) of the starch-free bran did not induce the formation of hydroxymethylfurfural and levulinic acid. Interestingly, the furfural level increased compared to the process, in which bran was treated hydrothermally without a preceding starch extraction. By separation of water-extractables prior to enzymatic hydrolysis, the free glucose purity was increased to 58%, however the yield of glucose decreased to 61%. Copyright © 2014 Elsevier Ltd. All rights reserved.

Consistency of Continuous Ambulatory Interstitial Glucose Monitoring Sensors.

PubMed

Wu, Pei T; Segovia, David E; Lee, Cathy C; Nguyen, Kim-Lien

2018-05-16

The abdominal region is the most common location for continuous glucose monitor (CGM) sensor insertion. However, a paucity of post-marketing data is available to demonstrate intra-individual consistency of CGM readings at different abdominal insertion sites. Healthy adults (fasting glucose (FG) < 5.5 mmol/L; BMI < 30 kg/m²) were recruited and a CGM sensor was placed on each side of the abdomen. Postprandial and continuous 48-h interstitial glucose levels were analyzed. There was no significant difference in the 3-h postprandial glucose (PPG) level derived from the left versus right CGM, which remained non-significant after adjusting for waist circumference or FG. Among the glucose levels recorded over 48-h, values on the left site were greater in 3.6% of the data points ( p < 0.05). After adjusting for waist circumference, only 0.5% of the glucose values remained significantly greater on the left ( p < 0.05). When adjusted for FG, similar results were observed. For both PPG and 48-h readings, the mean absolute relative difference was not significant between the two abdominal sites. CGM-derived glucose measures were highly consistent between the left and right abdomen during both the postprandial and post-absorptive periods.

Thiamazole Pretreatment Lowers the (131)I Activity Needed to Cure Hyperthyroidism in Patients With Nodular Goiter.

PubMed

Kyrilli, Aglaia; Tang, Bich-Ngoc-Thanh; Huyge, Valérie; Blocklet, Didier; Goldman, Serge; Corvilain, Bernard; Moreno-Reyes, Rodrigo

2015-06-01

Relatively low radioiodine uptake (RAIU) represents a common obstacle for radioiodine ((131)I) therapy in patients with multinodular goiter complicated by hyperthyroidism. To evaluate whether thiamazole (MTZ) pretreatment can increase (131)I therapeutic efficacy. Twenty-two patients with multinodular goiter, subclinical hyperthyroidism, and RAIU < 50% were randomized to receive either a low-iodine diet (LID; n = 10) or MTZ 30 mg/d (n = 12) for 42 days. Thyroid function and 24-hour RAIU were measured before and after treatment. Thyroid volume was evaluated by either magnetic resonance imaging or single photon emission computed tomography. Mean 24-hour RAIU increased significantly from 32 ± 10% to 63 ± 18% in the MTZ group (P < .001). Consequently, there was a 31% decrease in the calculated median therapeutic (131)I activity after MTZ (P < .05). No significant changes in 24-hour RAIU were observed after diet. In the MTZ group, median serum TSH levels increased significantly by 9% and mean serum free T4 and free T3 concentrations decreased by 22% and 15%, respectively, whereas no changes in thyroid function were observed in the LID group. Thyroid volume did not significantly change in either of the two groups. At 12 months after radioiodine treatment, median serum TSH was within the normal range in both groups. MTZ treatment before (131)I therapy resulted in an average 2-fold increase in thyroid RAIU and enhanced the efficiency of radioiodine therapy assessed at 12 months. MTZ pretreatment is therefore a safe, easily accessible alternative to recombinant human TSH stimulation and a more effective option than LID.

[Results of radioiodine therapy in different forms of hyperthyroidism in relation to the planned dosage].

PubMed

Moser, E

1992-07-01

The aim of this study was to assess the efficacy of radioiodine therapy (131J) in a large group (n = 925) of hyperthyroid patients treated at two major departments of nuclear medicine (Freiburg, abbr. FR, and Munich, abbr. M). 761 patients suffered from non-immunogenic hyperthyroidism (Plummer's disease) and the remaining 164 patients from immunogenic hyperthyroidism (Graves' disease). In these cases, radioiodine therapy using doses between 60 and 80 Gy proved ineffective, FR (80 Gy) recording 28% success and M (60 Gy) 54%. A dose of 150 Gy, however, is successful in more than 80% of the cases: FR 81%, M86%. However, the incidence rate of hypothyroidism increases consecutively with 150 Gy: FR 49%, M 62%. In patients suffering from Plummer's disease, the solitary autonomous nodule can be eliminated by radioiodine therapy (400 Gy) with a high rate of success (95%); the same applies to multinodular autonomous adenomas. The therapeutic concept applying a dose of 400 Gy to the total functional autonomous tissue (delineated by ultrasound) yields slightly better results (95%) than 150 Gy applied to thyroid gland (M88%, FR82%). This dosimetric compromise is a practicable alternative which is tolerably successful. In patients suffering from disseminated non-immunogenic hyperthyroidism, a dose of 150 Gy applied to the entire organ succeeds in 85% of the cases. The rate of hypothyroidism resulting from these dose recommendations is the lesser evil compared to residual or recurrent hyperthyroidism, since hypothyroid patients can be treated without any problem with thyroid hormones.

Synthesis and biological evaluation of novel radioiodinated imidazopyridine derivatives for amyloid-β imaging in Alzheimer's disease.

PubMed

Chen, Chun-Jen; Bando, Kazunori; Ashino, Hiroki; Taguchi, Kazumi; Shiraishi, Hideaki; Fujimoto, Osuke; Kitamura, Chiemi; Matsushima, Satoshi; Fujinaga, Masayuki; Zhang, Ming-Rong; Kasahara, Hiroyuki; Minamizawa, Takao; Jiang, Cheng; Ono, Maiko; Higuchi, Makoto; Suhara, Tetsuya; Yamada, Kazutaka; Ji, Bin

2014-08-01

Non-invasive detection for amyloid-β peptide (Aβ) deposition has important significance for the early diagnosis and medical intervention for Alzheimer's disease (AD). In this study, we developed a series of imidazopyridine derivatives as potential imaging agents for single-photon emission computed tomography (SPECT). Two of them, compounds DRK092 and DRM106, showed higher affinity for synthetic human Aβ 1-40 fibrils than did the well-known amyloid-imaging agent IMPY. A metabolite analysis revealed brain-permeable radioactive metabolites of (125)I-labeled DRK092 and IMPY; no radioactive metabolites from (125)I-labeled DRM106 ([(125)I]DRM106) were detected. In addition, in vitro autoradiography clearly demonstrated specific binding of [(125)I]DRM106 in the hippocampal region of AD enriched with Aβ plaques. Thus, our results strongly suggested that compound DRM106 can be used as an imaging agent for SPECT to detect Aβ deposition in AD brain. Copyright © 2014 Elsevier Ltd. All rights reserved.

Methane adsorption capacity on graphene derived from glucose and ferric chloride

NASA Astrophysics Data System (ADS)

Ismail, M. S.; Yusof, N.; Yusop, M. Zamri; Ismail, A. F.; Nasri, N. S.; Othman, F. E. Che

2018-05-01

This study examines the methane adsorption capacity using graphene derived from glucose and ferric chloride (FeCl3). The graphene was prepared via simple method by dissolution of glucose and FeCl3 in water, vaporization of water in oven, and calcination process in quartz furnace. Graphene was successfully produced with impregnation ratio of glucose and FeCl3 at 1:1 and calcination temperature of 650 °C. The prepared graphene subsequently underwent a volumetric adsorption setup, to measure the adsorption capacity of methane (CH4). The highest CH4 adsorption capacity obtained was 6.37 mmol/g at 3.5 bar and 298 K for 40 minutes. These result shows that the prepared graphene displayed good adsorption characteristic for CH4.

Direct evidence for activity-dependent glucose phosphorylation in neurons with implications for the astrocyte-to-neuron lactate shuttle

PubMed Central

Patel, Anant B.; Lai, James C. K.; Chowdhury, Golam M. I.; Hyder, Fahmeed; Rothman, Douglas L.; Shulman, Robert G.; Behar, Kevin L.

2014-01-01

Previous 13C magnetic resonance spectroscopy experiments have shown that over a wide range of neuronal activity, approximately one molecule of glucose is oxidized for every molecule of glutamate released by neurons and recycled through astrocytic glutamine. The measured kinetics were shown to agree with the stoichiometry of a hypothetical astrocyte-to-neuron lactate shuttle model, which predicted negligible functional neuronal uptake of glucose. To test this model, we measured the uptake and phosphorylation of glucose in nerve terminals isolated from rats infused with the glucose analog, 2-fluoro-2-deoxy-d-glucose (FDG) in vivo. The concentrations of phosphorylated FDG (FDG6P), normalized with respect to known neuronal metabolites, were compared in nerve terminals, homogenate, and cortex of anesthetized rats with and without bicuculline-induced seizures. The increase in FDG6P in nerve terminals agreed well with the increase in cortical neuronal glucose oxidation measured previously under the same conditions in vivo, indicating that direct uptake and oxidation of glucose in nerve terminals is substantial under resting and activated conditions. These results suggest that neuronal glucose-derived pyruvate is the major oxidative fuel for activated neurons, not lactate-derived from astrocytes, contradicting predictions of the original astrocyte-to-neuron lactate shuttle model under the range of study conditions. PMID:24706914

Direct evidence for activity-dependent glucose phosphorylation in neurons with implications for the astrocyte-to-neuron lactate shuttle.

PubMed

Patel, Anant B; Lai, James C K; Chowdhury, Golam M I; Hyder, Fahmeed; Rothman, Douglas L; Shulman, Robert G; Behar, Kevin L

2014-04-08

Previous (13)C magnetic resonance spectroscopy experiments have shown that over a wide range of neuronal activity, approximately one molecule of glucose is oxidized for every molecule of glutamate released by neurons and recycled through astrocytic glutamine. The measured kinetics were shown to agree with the stoichiometry of a hypothetical astrocyte-to-neuron lactate shuttle model, which predicted negligible functional neuronal uptake of glucose. To test this model, we measured the uptake and phosphorylation of glucose in nerve terminals isolated from rats infused with the glucose analog, 2-fluoro-2-deoxy-D-glucose (FDG) in vivo. The concentrations of phosphorylated FDG (FDG6P), normalized with respect to known neuronal metabolites, were compared in nerve terminals, homogenate, and cortex of anesthetized rats with and without bicuculline-induced seizures. The increase in FDG6P in nerve terminals agreed well with the increase in cortical neuronal glucose oxidation measured previously under the same conditions in vivo, indicating that direct uptake and oxidation of glucose in nerve terminals is substantial under resting and activated conditions. These results suggest that neuronal glucose-derived pyruvate is the major oxidative fuel for activated neurons, not lactate-derived from astrocytes, contradicting predictions of the original astrocyte-to-neuron lactate shuttle model under the range of study conditions.

ZIF-67 derived porous Co3O4 hollow nanopolyhedron functionalized solution-gated graphene transistors for simultaneous detection of glucose and uric acid in tears.

PubMed

Xiong, Can; Zhang, Tengfei; Kong, Weiyu; Zhang, Zhixiang; Qu, Hao; Chen, Wei; Wang, Yanbo; Luo, Linbao; Zheng, Lei

2018-03-15

Biomarkers in tears have attracted much attention in daily healthcare sensing and monitoring. Here, highly sensitive sensors for simultaneous detection of glucose and uric acid are successfully constructed based on solution-gated graphene transistors (SGGTs) with two separate Au gate electrodes, modified with GOx-CHIT and BSA-CHIT respectively. The sensitivity of the SGGT is dramatically improved by co-modifying the Au gate with ZIF-67 derived porous Co 3 O 4 hollow nanopolyhedrons. The sensing mechanism for glucose sensor is attributed to the reaction of H 2 O 2 generated by the oxidation of glucose near the gate, while the sensing mechanism for uric acid is due to the direct electro-oxidation of uric acid molecules on the gate. The optimized glucose and uric acid sensors show the detection limits both down to 100nM, far beyond the sensitivity required for non-invasive detection of glucose and uric acid in tears. The glucose and uric acid in real tear samples was quantitatively detected at 323.2 ± 16.1μM and 98.5 ± 16.3μM by using the functionalized SGGT device. Due to the low-cost, high-biocompatibility and easy-fabrication features of the ZIF-67 derived porous Co 3 O 4 hollow nanopolyhedron, they provide excellent electrocatalytic nanomaterials for enhancing sensitivity of SGGTs for a broad range of disease-related biomarkers. Copyright © 2017 Elsevier B.V. All rights reserved.

Isoalantolactone derivative promotes glucose utilization in skeletal muscle cells and increases energy expenditure in db/db mice via activating AMPK-dependent signaling.

PubMed

Arha, Deepti; Ramakrishna, E; Gupta, Anand P; Rai, Amit K; Sharma, Aditya; Ahmad, Ishbal; Riyazuddin, Mohammed; Gayen, Jiaur R; Maurya, Rakesh; Tamrakar, Akhilesh K

2018-01-15

Augmenting glucose utilization and energy expenditure in skeletal muscle via AMP-activated protein kinase (AMPK) is an imperative mechanism for the management of type 2 diabetes. Chemical derivatives (2a-2h, 3, 4a-4d, 5) of the isoalantolactone (K007), a bioactive molecule from roots of Inula racemosa were synthesized to optimize the bioactivity profile to stimulate glucose utilization in skeletal muscle cells. Interestingly, 4a augmented glucose uptake, driven by enhanced translocation of glucose transporter 4 (GLUT4) to cell periphery in L6 rat skeletal muscle cells. The effect of 4a was independent to phosphatidylinositide-3-kinase (PI-3-K)/Akt pathway, but mediated through Liver kinase B1 (LKB1)/AMPK-dependent signaling, leading to activation of downstream targets acetyl coenzyme A carboxylase (ACC) and sterol regulatory element binding protein 1c (SREBP-1c). In db/db mice, 4a administration decreased blood glucose level and improved body mass index, lipid parameters and glucose tolerance associated with elevation of GLUT4 expression in skeletal muscle. Moreover, 4a increased energy expenditure via activating substrate utilization and upregulated the expression of thermogenic transcription factors and mitochondrial proteins in skeletal muscle, suggesting the regulation of energy balance. These findings suggest the potential implication of isoalantolactone derivatives for the management of diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical analysis and antihyperglycemic activity of an original extract from burdock root (Arctium lappa).

PubMed

Tousch, Didier; Bidel, Luc P R; Cazals, Guillaume; Ferrare, Karine; Leroy, Jeremy; Faucanié, Marie; Chevassus, Hugues; Tournier, Michel; Lajoix, Anne-Dominique; Azay-Milhau, Jacqueline

2014-08-06

In the present study, we obtained a dried burdock root extract (DBRE) rich in caffeoylquinic acids derivatives. We performed the chemical characterization of DBRE and explored its antihyperglycemic potential in both in vitro and in vivo experiments. Chemical analysis of DBRE using LC-MS and GC-MS revealed the presence of a great majority of dicaffeoylquinic acid derivatives (75.4%) of which 1,5-di-O-caffeoyl-4-O-maloylquinic acid represents 44% of the extract. In the in vitro experiments, DBRE is able to increase glucose uptake in cultured L6 myocytes and to decrease glucagon-induced glucose output from rat isolated hepatocytes together with a reduction of hepatic glucose 6-phosphatase activity. DBRE did not increase insulin secretion in the INS-1 pancreatic β-cell line. In vivo, DBRE improves glucose tolerance both after intraperitoneal and oral subchronic administration. In conclusion, our data demonstrate that DBRE constitutes an original set of caffeoylquinic acid derivatives displaying antihyperglycemic properties.

Bronchoalveolar carcinoma of lung masquerading as iodine avid metastasis in a patient with minimally invasive follicular carcinoma of thyroid.

PubMed

Malhotra, Gaurav; Nair, Narendra; Menon, Hari; Gujral, Sumit; Abhyankar, Amit; Baghel, Nawab S; Awasare, Sushama; Nabar, Swapna J; Abhyankar, Suman; Kand, Purushottam G

2008-01-01

A 52-year-old man with follicular thyroid carcinoma was administered 182 mCi of radioiodine (I-131) a month after total thyroidectomy. Post-therapy scan revealed diffuse uptake of radioiodine in the apical left lung. CT-guided biopsy of this mass revealed mucinous bronchoalveolar carcinoma. Immunohistochemistry for thyroglobulin was negative. An FDG PET scan showed avid uptake in the lung mass. Surgery was ruled out, so he was given chemotherapy, without benefit. The lesion continued to show I-131 uptake even while on daily T3 substitution, suggesting that the mass was thyroid stimulating hormone-independent. Because the mass showed I-131 uptake and chemotherapy was not beneficial, it was decided to treat with I-131. He was continued on T3 substitution therapy and was given 209 mCi of I-131. Follow-up CT scan a few weeks later reported a 1-cm all round reduction of the mass. I-131 scan showed avid tracer uptake in the mass. This case suggests the possibility of this therapeutic option in nonthyroidal tumors that may concentrate radioiodine.

Radioiodine therapy in elderly patients with subclinical hyperthyroidism due to non-voluminous nodular goiter and its effect on bone metabolism.

PubMed

Rosario, Pedro Weslley

2013-03-01

To evaluate 131I therapy in elderly patients with subclinical hyperthyroidism (SCH) due to nodular disease and who did not receive antithyroid drugs (ATDs), and the effect of the treatment on bone metabolism. Thirty-six patients with TSH ≤ 0.1 mIU/L and non-voluminous goiter (< 60 cm³) were studied. Bone mineral density (BMD) was assessed in 17 women with osteopenia. Mean 24-h 131I uptake was 17.5%. Symptoms of thyrotoxicosis were reported by two (5.5%) patients in the first week after therapy. One year after radioiodine treatment, SCH was resolved in 30 (83.3%) patients, and hypothyroidism was detected in one (2.7%). In the patients in whom TSH returned to normal, femoral and lumbar spine BMD increased by 1.9% and 1.6%, respectively, in average. In elderly patients with SCH and non-voluminous goiter, radioiodine not preceded by ATDs is a safe and effective therapeutic alternative. Resolution of SCH has beneficial effects on BMD in postmenopausal women with osteopenia.

Amino acids rather than glucose account for the majority of cell mass in proliferating mammalian cells

PubMed Central

Hosios, Aaron M.; Hecht, Vivian C.; Danai, Laura V.; Johnson, Marc O.; Rathmell, Jeffrey C.; Steinhauser, Matthew L.; Manalis, Scott R.; Vander Heiden, Matthew G.

2016-01-01

Cells must duplicate their mass in order to proliferate. Glucose and glutamine are the major nutrients consumed by proliferating mammalian cells, but the extent to which these and other nutrients contribute to cell mass is unknown. We quantified the fraction of cell mass derived from different nutrients and find that the majority of carbon mass in cells is derived from other amino acids, which are consumed at much lower rates than glucose and glutamine. While glucose carbon has diverse fates, glutamine contributes most to protein, and this suggests that glutamine’s ability to replenish TCA cycle intermediates (anaplerosis) is primarily used for amino acid biosynthesis. These findings demonstrate that rates of nutrient consumption are indirectly associated with mass accumulation and suggest that high rates of glucose and glutamine consumption support rapid cell proliferation beyond providing carbon for biosynthesis. PMID:26954548

An Introductory Organic Chemistry Review Homework Exercise: Deriving Potential Mechanisms for Glucose Ring Opening in Mutarotation

ERIC Educational Resources Information Center

Murdock, Margaret; Holman, R. W.; Slade, Tyler; Clark, Shelley L. D.; Rodnick, Kenneth J.

2014-01-01

A unique homework assignment has been designed as a review exercise to be implemented near the end of the one-year undergraduate organic chemistry sequence. Within the framework of the exercise, students derive potential mechanisms for glucose ring opening in the aqueous mutarotation process. In this endeavor, 21 general review principles are…

Quantifying rates of glucose production in vivo following an intraperitoneal tracer bolus.

PubMed

Wang, Sheng-Ping; Zhou, Dan; Yao, Zuliang; Satapati, Santhosh; Chen, Ying; Daurio, Natalie A; Petrov, Aleksandr; Shen, Xiaolan; Metzger, Daniel; Yin, Wu; Nawrocki, Andrea R; Eiermann, George J; Hwa, Joyce; Fancourt, Craig; Miller, Corin; Herath, Kithsiri; Roddy, Thomas P; Slipetz, Deborah; Erion, Mark D; Previs, Stephen F; Kelley, David E

2016-12-01

Aberrant regulation of glucose production makes a critical contribution to the impaired glycemic control that is observed in type 2 diabetes. Although isotopic tracer methods have proven to be informative in quantifying the magnitude of such alterations, it is presumed that one must rely on venous access to administer glucose tracers which therein presents obstacles for the routine application of tracer methods in rodent models. Since intraperitoneal injections are readily used to deliver glucose challenges and/or dose potential therapeutics, we hypothesized that this route could also be used to administer a glucose tracer. The ability to then reliably estimate glucose flux would require attention toward setting a schedule for collecting samples and choosing a distribution volume. For example, glucose production can be calculated by multiplying the fractional turnover rate by the pool size. We have taken a step-wise approach to examine the potential of using an intraperitoneal tracer administration in rat and mouse models. First, we compared the kinetics of [U- 13 C]glucose following either an intravenous or an intraperitoneal injection. Second, we tested whether the intraperitoneal method could detect a pharmacological manipulation of glucose production. Finally, we contrasted a potential application of the intraperitoneal method against the glucose-insulin clamp. We conclude that it is possible to 1) quantify glucose production using an intraperitoneal injection of tracer and 2) derive a "glucose production index" by coupling estimates of basal glucose production with measurements of fasting insulin concentration; this yields a proxy for clamp-derived assessments of insulin sensitivity of endogenous production. Copyright © 2016 the American Physiological Society.

Insulin sensitivity and metabolic flexibility following exercise training among different obese insulin-resistant phenotypes.

PubMed

Malin, Steven K; Haus, Jacob M; Solomon, Thomas P J; Blaszczak, Alecia; Kashyap, Sangeeta R; Kirwan, John P

2013-11-15

Impaired fasting glucose (IFG) blunts the reversal of impaired glucose tolerance (IGT) after exercise training. Metabolic inflexibility has been implicated in the etiology of insulin resistance; however, the efficacy of exercise on peripheral and hepatic insulin sensitivity or substrate utilization in adults with IFG, IGT, or IFG + IGT is unknown. Twenty-four older (66.7 ± 0.8 yr) obese (34.2 ± 0.9 kg/m(2)) adults were categorized as IFG (n = 8), IGT (n = 8), or IFG + IGT (n = 8) according to a 75-g oral glucose tolerance test (OGTT). Subjects underwent 12-wk of exercise (60 min/day for 5 days/wk at ∼85% HRmax) and were instructed to maintain a eucaloric diet. A euglycemic hyperinsulinemic clamp (40 mU·m(2)·min(-1)) with [6,6-(2)H]glucose was used to determine peripheral and hepatic insulin sensitivity. Nonoxidative glucose disposal and metabolic flexibility [insulin-stimulated respiratory quotient (RQ) minus fasting RQ] were also assessed. Glucose incremental area under the curve (iAUCOGTT) was calculated from the OGTT. Exercise increased clamp-derived peripheral and hepatic insulin sensitivity more in adults with IFG or IGT alone than with IFG + IGT (P < 0.05). Exercise reduced glucose iAUCOGTT in IGT only (P < 0.05), and the decrease in glucose iAUCOGTT was inversely correlated with the increase in peripheral but not hepatic insulin sensitivity (P < 0.01). Increased clamp-derived peripheral insulin sensitivity was also correlated with enhanced metabolic flexibility, reduced fasting RQ, and higher nonoxidative glucose disposal (P < 0.05). Adults with IFG + IGT had smaller gains in clamp-derived peripheral insulin sensitivity and metabolic flexibility, which was related to blunted improvements in postprandial glucose. Additional work is required to assess the molecular mechanism(s) by which chronic hyperglycemia modifies insulin sensitivity following exercise training.

A selective glucose sensor: the cooperative effect of monoboronic acid-modified poly(amidoamine) dendrimers.

PubMed

Tsai, Ching-Hua; Tang, Yi-Hsuan; Chen, Hui-Ting; Yao, Yi-Wen; Chien, Tun-Cheng; Kao, Chai-Lin

2018-05-01

Selective glucose binding was identified through five generations of monoboronic acid-functionalized PAMAM dendrimers. The best selectivity obtained when using G3 dendrimers (1b) generated 71.1, 94.9, and 1309 times stronger binding than when using galactose, fructose, and lactose, respectively. Further experiments using dendrimer analogues and glucose derivatives suggested that two nearby monoboronic acids cooperatively bound one glucose.

Naphthaldimine-based simple glucose derivative as a highly selective sensor for colorimetric detection of Cu2+ ion in aqueous media

NASA Astrophysics Data System (ADS)

Dolai, Bholanath; Bhaumik, Atanu; Pramanik, Nabakumar; Ghosh, Kalyan Sundar; Atta, Ananta Kumar

2018-07-01

Naphthaldimine-based glucose derivatives 1 and 3 have been designed, synthesized and characterized. In aqueous media, glucose derivative 1, exhibited high selectivity and sensitivity towards Cu2+ ion in comparison with various cations and anions. In presence of Cu2+, sensor 1 has provided significant naked-eye detectable color change. The formation of 1-Cu2+ complex has been analyzed by UV-vis spectroscopy, 1H NMR titration experiments, mass spectrometry and DFT (density functional theory) calculations. Limit of detection of 1 as a colorimetric sensor for Cu2+ ion is found to be 0.23 μM, much lower than recommended value of World Health Organization (WHO), which makes to Cu2+ sensor 1 more effective and useful.

21 CFR 184.1318 - Glucono delta-lactone.

Code of Federal Regulations, 2012 CFR

2012-04-01

... crystallization from the aqueous solution of gluconic acid. Gluconic acid may be produced by the oxidation of D-glucose with bromine water, by the oxidation of D-glucose by microorganisms that are nonpathogenic and nontoxicogenic to man or other animals, or by the oxidation of D-glucose with enzymes derived from these...

21 CFR 184.1318 - Glucono delta-lactone.

Code of Federal Regulations, 2013 CFR

2013-04-01

... crystallization from the aqueous solution of gluconic acid. Gluconic acid may be produced by the oxidation of D-glucose with bromine water, by the oxidation of D-glucose by microorganisms that are nonpathogenic and nontoxicogenic to man or other animals, or by the oxidation of D-glucose with enzymes derived from these...

On the occurrence of hypothyroidism after radioiodine resection (in German)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farschidpur, D.; Meiisel, P.

1963-02-01

An attempt was made to determine the dose of radioiodine in the treatment of hyperthyroidism with reference to the number of Cs and rep values. It was proved desirable to administer no more than 8 mC and 30,000 rep. An analysis of patients treated between 1956 and 1961 revealed six permanent cases of hypothyroidism; each had been treated with a greater dose than the above. The occurrence of hynofunction in cases treated with a dose greater than the above is compared statistically with cases treated with smaller doses. A number of examples are discussed.

Struma Ovarii With Hyperthyroidism.

PubMed

Ang, Lynn P; Avram, Anca M; Lieberman, Richard W; Esfandiari, Nazanene H

2017-06-01

We report the case of a 61-year-old woman with persistent thyrotoxicosis for 7 years despite low thyroidal radioiodine uptake and methimazole treatment. Her initial I whole-body scan (WBS) was read as negative. Upon evaluation in our institution, she remained hyperthyroid after discontinuation of methimazole. Repeat WBS with SPECT/CT revealed low 24-hour thyroidal uptake (RAIU = 2%) and intensely focal radioiodine uptake in a large heterogeneous left pelvic mass, consistent with left adnexal struma ovarii. Resection of this mass confirmed benign struma ovarii. This case illustrates the advantage of fusion SPECT/CT imaging with planar I-WBS for diagnosis of extrathyroidal thyrotoxicosis.

Pharmacokinetics and tissue distribution of parenterally administered human alpha-lymphotoxin in normal and meth-A tumor-bearing BALB/c mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Averbook, B.J.; Jeffes, E.B.; Yamamoto, R.S.

1989-08-01

These in vivo studies examine the pharmacokinetics of parenterally administered purified, native human alpha-lymphotoxin (LT) in normal and Meth-A bearing BALB/c mice. We found that the lytic activity of alpha-LT was inactivated within 5 h in the blood of both normal and tumor-bearing mice in vivo. However, LT bioactivity in vitro was not affected by incubation with fresh serum. Radioiodinated LT was rapidly sequestered in the kidneys of both normal and tumor-bearing animals. Systemically administered, radioiodinated LT did not selectively localize in tumor tissues.

PROCEEDINGS OF THE CONFERENCE ON RADIOIODINE SPONSORED BY THE ARGONNE CANCER RESEARCH HOSPITAL, UNITED STATES ATOMIC ENERGY COMMISSION, AND THE CLINICS OF THE UNIVERSITY OF CHICAGO, NOVEMBER 5 AND 6, 1956, CHICAGO, ILLINOIS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clark, D.E. ed.

1958-10-31

Applications of the various iodine isotopes in diagnosis and therapy are discussed. Problems of dosimetry and radiation exposure to patients and hospital personnel are considered. Some quantitative aspects of radiation damage in mammals relevant to the clinical use of radioiodine are reviewed. Emphasis is placed on applications of iodine-131 in diagnosis and therapy of hyperthyroidism and hypothyroidism; in the treatmeat of thyroid carcinoma; and in thyroid ablation for cardiac disease. 54 references. (C.H.)

Guidelines for radioiodinated MIBG scintigraphy in children.

PubMed

Olivier, Pierre; Colarinha, Paula; Fettich, Jure; Fischer, Sibylle; Frökier, Jörgen; Giammarile, Francesco; Gordon, Isky; Hahn, Klaus; Kabasakal, Levent; Mann, Mike; Mitjavila, Mercedes; Piepsz, Amy; Porn, Ute; Sixt, Rune; van Velzen, Jeannette

2003-05-01

These guidelines on the use of radioiodinated (99m)Tc-MIBG scintigraphy in children, which summarise the views of the Paediatric Committee of the European Association of Nuclear Medicine, provide a framework which may prove helpful to nuclear medicine teams in daily practice. They have been influenced by the conclusions of the "Consensus Guidelines for MIBG Scintigraphy" (Paris, November 6, 1997) of the European Neuroblastoma Group and by those of the Oncological Committee of the French Society of Nuclear Medicine. The guidelines should be taken in the context of "good practice" and any local/national rules which apply to nuclear medicine examinations.

Current practice of radioiodine treatment in the management of differentiated thyroid cancer in Germany.

PubMed

Hoelzer, S; Steiner, D; Bauer, R; Reiners, C; Farahati, J; Hundahl, S A; Dudeck, J

2000-10-01

This prospective, observational study of a cohort of thyroid cancer patients in Germany focusses on the "real-world" practice in the management of thyroid cancer patients. This report includes data from 2376 patients with primary differentiated thyroid carcinoma first diagnosed in the year 1996. The study reveals considerable differences in actual practice concerning surgery and radioiodine treatment. The results indicate that consensus is lacking with respect to the multimodality treatment approach for differentiated thyroid carcinoma. Our analysis represents the most current and comprehensive national assessment of presenting patient characteristics, diagnostic tests, treatment and complications for thyroid cancer.

Seasonal variability of iodine and selenium in surface and groundwater as a factor that may contribute to iodine isotope balance in the thyroid gland and its irradiation in case of radioiodine contamination during accidents at the NPP

NASA Astrophysics Data System (ADS)

Korobova, Elena; Kolmykova, Lyudmila; Ryzhenko, Boris; Berezkin, Viktor; Saraeva, Anastasia

2016-04-01

Radioiodine release to the environment during the accident at the Chernobyl NPP led to the increased risk of the thyroid cancer cases within the contaminated areas, the effect being aggravated in conditions of stable iodine and selenium deficiency in local food chains. Although the drinking water iodine is usually believed to contribute not more than 10% to local diet, our estimations accounting of water content in other products and several regional studies (e.g. India and Australia) proved its portion to be at least twice as much. As radioiodine isotopes are short-lived, their absorption depends greatly on stable iodine and selenium sufficiency in thyroid gland in the first few days of contamination and seasonal variation of stable iodine and selenium in local sources of drinking water may be significant as modifying the resulting thyroid irradiation in different seasons of the year. The main goal of the study was to evaluate seasonal variation of levels of iodine and selenium in natural waters of the Bryansk region as a possible factor affecting the radioiodine intake by thyroid gland of animals and humans in case of radioiodine contamination during the accident. Seasonal I and Se concentration was measured in the years of 2014 and 2015 at 14 test points characterizing surface (river and lake) and drinking groundwater. Obtained data proved considerable seasonal variation of I and Se concentration in natural waters (3,7-8,1 μg/l and 0,04-0,4 μg/l respectively) related to physico-chemical water parameters, such as pH, Eh and fluctuations in concentration of dissolved organic matter. The widest I and Se seasonal variability was observed in surface and well waters, maximum I level being found in autumn at the end of vegetation period characterized by active I leaching from the decomposed organic residues by long lasting precipitations. The content of selenium in the surface waters during summer-autumn (0,06-0,3 μg/l) was higher than in spring (0,04-0,05 μg/l). In drinking water from centralized supply pipeline low concentration of both elements was also registered in spring (3,7-4,3 μg/l (I) and 0,04-0,08 μg/l (Se)). Accounting of the fact that both the Chernobyl and Fukushima accidents took place in spring, we hypothesis that low iodine intake with water may have contributed to the risk of higher radioiodine intake by thyroid gland in the period of the accident. The work was supported the Russian Foundation for Basic Research (grant 13-05-00823).

Electrocardiogram-Based Sleep Spectrogram Measures of Sleep Stability and Glucose Disposal in Sleep Disordered Breathing

PubMed Central

Pogach, Melanie S.; Punjabi, Naresh M.; Thomas, Neil; Thomas, Robert J.

2012-01-01

Study Objectives: Sleep disordered breathing (SDB) is independently associated with insulin resistance, glucose intolerance, and type 2 diabetes mellitus. Experimental sleep fragmentation has been shown to impair insulin sensitivity. Conventional electroencephalogram (EEG)-based sleep-quality measures have been inconsistently associated with indices of glucose metabolism. This analysis explored associations between glucose metabolism and an EEG-independent measure of sleep quality, the sleep spectrogram, which maps coupled oscillations of heart-rate variability and electrocardiogram (ECG)-derived respiration. The method allows improved characterization of the quality of stage 2 non-rapid eye movement (NREM) sleep. Design: Cross-sectional study. Setting: N/A. Participants: Nondiabetic subjects with and without SDB (n = 118) underwent the frequently sampled intravenous glucose tolerance test (FSIVGTT) and a full-montage polysomnogram. The sleep spectrogram was generated from ECG collected during polysomnography. Interventions: N/A. Measurements and Results: Standard polysomnographic stages (stages 1, 2, 3+4, and rapid eye movement [REM]) were not associated with the disposition index (DI) derived from the FSIVGTT. In contrast, spectrographic high-frequency coupling (a marker of stable or “effective” sleep) duration was associated with increased, and very-low-frequency coupling (a marker of wake/REM/transitions) associated with reduced DI. This relationship was noted after adjusting for age, sex, body mass index, slow wave sleep, total sleep time, stage 1, the arousal index, and the apnea-hypopnea index. Conclusions: ECG-derived sleep-spectrogram measures of sleep quality are associated with alterations in glucose-insulin homeostasis. This alternate mode of estimating sleep quality could improve our understanding of sleep and sleep-breathing effects on glucose metabolism. Citation: Pogach MS; Punjabi NM; Thomas N; Thomas RJ. Electrocardiogram-based sleep spectrogram measures of sleep stability and glucose disposal in sleep disordered breathing. SLEEP 2012;35(1):139-148. PMID:22215928

Synthesis and evaluation of ethyleneoxylated and allyloxylated chalcone derivatives for imaging of amyloid β plaques by SPECT.

PubMed

Fuchigami, Takeshi; Yamashita, Yuki; Haratake, Mamoru; Ono, Masahiro; Yoshida, Sakura; Nakayama, Morio

2014-05-01

We report radioiodinated chalcone derivatives as new SPECT imaging probes for amyloid β (Aβ) plaques. The monoethyleneoxy derivative 2 and allyloxy derivative 8 showed a high affinity for Aβ(1-42) aggregates with Ki values of 24 and 4.5 nM, respectively. Fluorescent imaging demonstrated that 2 and 8 clearly stained thioflavin-S positive Aβ plaques in the brain sections of Tg2576 transgenic mice. In vitro autoradiography revealed that [(125)I]2 displayed no clear accumulation toward Aβ plaques in the brain sections of Tg2576 mice, whereas the accumulation pattern of [(125)I]8 matched with the presence of Aβ plaques both in the brain sections of Tg2576 mice and an AD patient. In biodistribution studies using normal mice, [(125)I]2 showed preferable in vivo pharmacokinetics (4.82%ID/g at 2 min and 0.45%ID/g at 60 min), while [(125)I]8 showed only a modest brain uptake (1.62%ID/g at 2 min) with slow clearance (0.56%ID/g at 60 min). [(125)I]8 showed prospective binding properties for Aβ plaques, although further structural modifications are needed to improve the blood brain barrier permeability and washout from brain. Copyright © 2014 Elsevier Ltd. All rights reserved.

Fructose Alters Intermediary Metabolism of Glucose in Human Adipocytes and Diverts Glucose to Serine Oxidation in the One–Carbon Cycle Energy Producing Pathway

PubMed Central

Varma, Vijayalakshmi; Boros, László G.; Nolen, Greg T.; Chang, Ching-Wei; Wabitsch, Martin; Beger, Richard D.; Kaput, Jim

2015-01-01

Increased consumption of sugar and fructose as sweeteners has resulted in the utilization of fructose as an alternative metabolic fuel that may compete with glucose and alter its metabolism. To explore this, human Simpson-Golabi-Behmel Syndrome (SGBS) preadipocytes were differentiated to adipocytes in the presence of 0, 1, 2.5, 5 or 10 mM of fructose added to a medium containing 5 mM of glucose representing the normal blood glucose concentration. Targeted tracer [1,2-13C2]-d-glucose fate association approach was employed to examine the influence of fructose on the intermediary metabolism of glucose. Increasing concentrations of fructose robustly increased the oxidation of [1,2-13C2]-d-glucose to 13CO2 (p < 0.000001). However, glucose-derived 13CO2 negatively correlated with 13C labeled glutamate, 13C palmitate, and M+1 labeled lactate. These are strong markers of limited tricarboxylic acid (TCA) cycle, fatty acid synthesis, pentose cycle fluxes, substrate turnover and NAD+/NADP+ or ATP production from glucose via complete oxidation, indicating diminished mitochondrial energy metabolism. Contrarily, a positive correlation was observed between glucose-derived 13CO2 formed and 13C oleate and doses of fructose which indicate the elongation and desaturation of palmitate to oleate for storage. Collectively, these results suggest that fructose preferentially drives glucose through serine oxidation glycine cleavage (SOGC pathway) one-carbon cycle for NAD+/NADP+ production that is utilized in fructose-induced lipogenesis and storage in adipocytes. PMID:26087138

Assessing the reliability of dose coefficients for exposure to radioiodine by members of the public, accounting for dosimetric and risk model uncertainties.

PubMed

Puncher, M; Zhang, W; Harrison, J D; Wakeford, R

2017-06-26

Assessments of risk to a specific population group resulting from internal exposure to a particular radionuclide can be used to assess the reliability of the appropriate International Commission on Radiological Protection (ICRP) dose coefficients used as a radiation protection device for the specified exposure pathway. An estimate of the uncertainty on the associated risk is important for informing judgments on reliability; a derived uncertainty factor, UF, is an estimate of the 95% probable geometric difference between the best risk estimate and the nominal risk and is a useful tool for making this assessment. This paper describes the application of parameter uncertainty analysis to quantify uncertainties resulting from internal exposures to radioiodine by members of the public, specifically 1, 10 and 20-year old females from the population of England and Wales. Best estimates of thyroid cancer incidence risk (lifetime attributable risk) are calculated for ingestion or inhalation of 129 I and 131 I, accounting for uncertainties in biokinetic model and cancer risk model parameter values. These estimates are compared with the equivalent ICRP derived nominal age-, sex- and population-averaged estimates of excess thyroid cancer incidence to obtain UFs. Derived UF values for ingestion or inhalation of 131 I for 1 year, 10-year and 20-year olds are around 28, 12 and 6, respectively, when compared with ICRP Publication 103 nominal values, and 9, 7 and 14, respectively, when compared with ICRP Publication 60 values. Broadly similar results were obtained for 129 I. The uncertainties on risk estimates are largely determined by uncertainties on risk model parameters rather than uncertainties on biokinetic model parameters. An examination of the sensitivity of the results to the risk models and populations used in the calculations show variations in the central estimates of risk of a factor of around 2-3. It is assumed that the direct proportionality of excess thyroid cancer risk and dose observed at low to moderate acute doses and incorporated in the risk models also applies to very small doses received at very low dose rates; the uncertainty in this assumption is considerable, but largely unquantifiable. The UF values illustrate the need for an informed approach to the use of ICRP dose and risk coefficients.

Two risk score models for predicting incident Type 2 diabetes in Japan.

PubMed

Doi, Y; Ninomiya, T; Hata, J; Hirakawa, Y; Mukai, N; Iwase, M; Kiyohara, Y

2012-01-01

Risk scoring methods are effective for identifying persons at high risk of Type 2 diabetes mellitus, but such approaches have not yet been established in Japan. A total of 1935 subjects of a derivation cohort were followed up for 14 years from 1988 and 1147 subjects of a validation cohort independent of the derivation cohort were followed up for 5 years from 2002. Risk scores were estimated based on the coefficients (β) of Cox proportional hazards model in the derivation cohort and were verified in the validation cohort. In the derivation cohort, the non-invasive risk model was established using significant risk factors; namely, age, sex, family history of diabetes, abdominal circumference, body mass index, hypertension, regular exercise and current smoking. We also created another scoring risk model by adding fasting plasma glucose levels to the non-invasive model (plus-fasting plasma glucose model). The area under the curve of the non-invasive model was 0.700 and it increased significantly to 0.772 (P < 0.001) in the plus-fasting plasma glucose model. The ability of the non-invasive model to predict Type 2 diabetes was comparable with that of impaired glucose tolerance, and the plus-fasting plasma glucose model was superior to it. The cumulative incidence of Type 2 diabetes was significantly increased with elevating quintiles of the sum scores of both models in the validation cohort (P for trend < 0.001). We developed two practical risk score models for easily identifying individuals at high risk of incident Type 2 diabetes without an oral glucose tolerance test in the Japanese population. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.

Comparative analysis of the countermeasures taken to mitigate exposure of the public to radioiodine following the Chernobyl and Fukushima accidents: lessons from both accidents.

PubMed

Uyba, Vladimir; Samoylov, Alexander; Shinkarev, Sergey

2018-04-01

In the case of a severe radiation accident at a nuclear power station, the most important radiation hazard for the public is internal exposure of the thyroid to radioiodine. The purposes of this paper were (i) to compare countermeasures conducted (following the Chernobyl and Fukushima accidents) aimed at mitigation of exposure to the thyroid for the public, (ii) to present comparative estimates of doses to the thyroid and (iii) to derive lessons from the two accidents. The scale and time of countermeasures applied in the early phase of the accidents (sheltering, evacuation, and intake of stable iodine to block the thyroid) and at a later time (control of 131I concentration in foodstuffs) have been described. After the Chernobyl accident, the estimation of the thyroid doses for the public was mainly based on direct thyroid measurements of ~400 000 residents carried out within the first 2 months. The highest estimates of thyroid doses to children reached 50 Gy. After the Fukushima accident, the estimation of thyroid doses was based on radioecological models due to a lack of direct thyroid measurements (only slightly more than 1000 residents were measured). The highest estimates of thyroid doses to children were a few hundred mGy. Following the Chernobyl accident, ingestion of 131I through cows' milk was the dominant pathway. Following the Fukushima accident, it appears that inhalation of contaminated air was the dominant pathway. Some lessons learned following the Chernobyl and Fukushima accidents have been presented in this paper.

Comparative analysis of the countermeasures taken to mitigate exposure of the public to radioiodine following the Chernobyl and Fukushima accidents: lessons from both accidents

PubMed Central

Uyba, Vladimir; Samoylov, Alexander; Shinkarev, Sergey

2018-01-01

Abstract In the case of a severe radiation accident at a nuclear power station, the most important radiation hazard for the public is internal exposure of the thyroid to radioiodine. The purposes of this paper were (i) to compare countermeasures conducted (following the Chernobyl and Fukushima accidents) aimed at mitigation of exposure to the thyroid for the public, (ii) to present comparative estimates of doses to the thyroid and (iii) to derive lessons from the two accidents. The scale and time of countermeasures applied in the early phase of the accidents (sheltering, evacuation, and intake of stable iodine to block the thyroid) and at a later time (control of 131I concentration in foodstuffs) have been described. After the Chernobyl accident, the estimation of the thyroid doses for the public was mainly based on direct thyroid measurements of ~400 000 residents carried out within the first 2 months. The highest estimates of thyroid doses to children reached 50 Gy. After the Fukushima accident, the estimation of thyroid doses was based on radioecological models due to a lack of direct thyroid measurements (only slightly more than 1000 residents were measured). The highest estimates of thyroid doses to children were a few hundred mGy. Following the Chernobyl accident, ingestion of 131I through cows’ milk was the dominant pathway. Following the Fukushima accident, it appears that inhalation of contaminated air was the dominant pathway. Some lessons learned following the Chernobyl and Fukushima accidents have been presented in this paper. PMID:29415268

Myeloperoxidase amplified high glucose-induced endothelial dysfunction in vasculature: Role of NADPH oxidase and hypochlorous acid.

PubMed

Tian, Rong; Ding, Yun; Peng, Yi-Yuan; Lu, Naihao

2017-03-11

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived reactive oxygen species (ROS) such as superoxide and hydrogen peroxide (H 2 O 2 ), have emerged as important molecules in the pathogenesis of diabetic endothelial dysfunction. Additionally, neutrophils-derived myeloperoxidase (MPO) and MPO-catalyzed hypochlorous acid (HOCl) play important roles in the vascular injury. However, it is unknown whether MPO can use vascular-derived ROS to induce diabetic endothelial dysfunction. In the present study, we demonstrated that NADPH oxidase was the main source of ROS formation in high glucose-cultured human umbilical vein endothelial cells (HUVECs), and played a critical role in high glucose-induced endothelial dysfunction such as cell apoptosis, loss of cell viability and reduction of nitric oxide (NO). However, the addition of MPO could amplify the high glucose-induced endothelial dysfunction which was inhibited by the presence of apocynin (NADPH oxidase inhibitor), catalase (H 2 O 2 scavenger), or methionine (HOCl scavenger), demonstrating the contribution of NADPH oxidase-H 2 O 2 -MPO-HOCl pathway in the MPO/high glucose-induced vascular injury. In high glucose-incubated rat aortas, MPO also exacerbated the NADPH oxidase-induced impairment of endothelium-dependent relaxation. Consistent with these in vitro data, in diabetic rat aortas, both MPO expresion and NADPH oxidase activity were increased while the endothelial function was simultaneously impaired. The results suggested that vascular-bound MPO could amplify high glucose-induced vascular injury in diabetes. MPO-NADPH oxidase-HOCl may represent an important pathogenic pathway in diabetic vascular diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Chinese Data of Efficacy of Low- and High-Dose Iodine-131 for the Ablation of Thyroid Remnant.

PubMed

Ma, Chao; Feng, Fang; Wang, Shaoyan; Fu, Hongliang; Wu, Shuqi; Ye, Zhiyi; Chen, Suyun; Wang, Hui

2017-06-01

Chinese data on the efficacy of low- and high-dose radioiodine for thyroid remnant are still absent. The aim of the study was to investigate whether a low dose of radioiodine is as effective as a high dose for remnant ablation in Chinese patients. Patients presenting for radioiodine ablation in the authors' department were included. Inclusion criteria were aged ≥16 years, total or near-total thyroidectomy, tumor-node-metastasis (TNM) stage of pT1-3, any N stage, and M0. All patients were randomly allocated to either the high-dose group of 3700 MBq or the low-dose group of 1850 MBq for remnant ablation. The response to treatment was defined as successful or unsuccessful after a six- to nine-month interval. Ablation was considered to be successful if patients fulfilled the following criteria: no tracer uptake in the thyroid bed on diagnosis whole-body scanning and a negative level of serum thyroglobulin. There were 327 patients enrolled between January 2013 and December 2014. More than 95% had papillary thyroid cancer. Data could be analyzed for 278 cases (M age  = 44 years; 71.6% women), 155 in the low-dose group and 123 in the high-dose group. The rate of initial successful ablation was 84.2% in all patients, 82.6% in the low-dose group, and 86.2% in the high-dose group. There was no difference between the two groups (p = 0.509). In Chinese patients with differentiated thyroid carcinoma, the low dose of 1850 MBq radioiodine activity is as effective as a high dose of 3700 MBq for thyroid remnant ablation.

Epidemiology, management and outcomes of Graves' disease-real life data.

PubMed

Hussain, Y S; Hookham, J C; Allahabadia, A; Balasubramanian, S P

2017-06-01

Treatment options in Graves' disease are clearly defined, but management practices and the perceptions of success are varied. The outcomes of treatment in large consecutive cohorts of Graves' disease have not been well characterised. The study describes the epidemiology, management strategies and medium term outcomes following anti-thyroid drug treatment, radio-iodine ablation and surgery in Graves' disease. All patients (n = 659) who received treatment for a new diagnosis of Graves' disease in secondary care over a 5 year period were included with a median (interquartile range) follow-up of 42.9 (29-57.5) months. The age adjusted incidence of adult onset Graves' disease in Sheffield, UK was 24.8 per 100,000 per year. Excluding 35 patients lost to follow-up, 93.1% (n = 581) were controlled on anti-thyroid drug treatment. Of these, 73.6% went into remission following withdrawal of anti-thyroid drugs; 5.2% were still undergoing initial therapy; 13.3% lost control whilst on anti-thyroid drugs; and 7.9% went on to have either surgery or radio-iodine ablation whilst controlled on anti-thyroid drugs. Of the 428 patients who achieved remission, 36.7% relapsed. Of 144 patients who had radio-iodine ablation treatment, 5.6% relapsed and needed further treatment. Of 119 patients having surgery, 5.2% had long-term hypoparathyroidism and none had documented long-term recurrent laryngeal nerve palsy. In the follow-up, 39.9% of patients underwent surgery or radio-iodine ablation with little morbidity. Up to two-thirds of patients who achieved remission did not relapse. Data on effectiveness and risks of treatments for Graves' disease presented in this study will help clinicians and patients in decision making.

Accuracy and optimal timing of activity measurements in estimating the absorbed dose of radioiodine in the treatment of Graves' disease

NASA Astrophysics Data System (ADS)

Merrill, S.; Horowitz, J.; Traino, A. C.; Chipkin, S. R.; Hollot, C. V.; Chait, Y.

2011-02-01

Calculation of the therapeutic activity of radioiodine 131I for individualized dosimetry in the treatment of Graves' disease requires an accurate estimate of the thyroid absorbed radiation dose based on a tracer activity administration of 131I. Common approaches (Marinelli-Quimby formula, MIRD algorithm) use, respectively, the effective half-life of radioiodine in the thyroid and the time-integrated activity. Many physicians perform one, two, or at most three tracer dose activity measurements at various times and calculate the required therapeutic activity by ad hoc methods. In this paper, we study the accuracy of estimates of four 'target variables': time-integrated activity coefficient, time of maximum activity, maximum activity, and effective half-life in the gland. Clinical data from 41 patients who underwent 131I therapy for Graves' disease at the University Hospital in Pisa, Italy, are used for analysis. The radioiodine kinetics are described using a nonlinear mixed-effects model. The distributions of the target variables in the patient population are characterized. Using minimum root mean squared error as the criterion, optimal 1-, 2-, and 3-point sampling schedules are determined for estimation of the target variables, and probabilistic bounds are given for the errors under the optimal times. An algorithm is developed for computing the optimal 1-, 2-, and 3-point sampling schedules for the target variables. This algorithm is implemented in a freely available software tool. Taking into consideration 131I effective half-life in the thyroid and measurement noise, the optimal 1-point time for time-integrated activity coefficient is a measurement 1 week following the tracer dose. Additional measurements give only a slight improvement in accuracy.

Juvenile hypothyroidism among two populations exposed to radioiodine.

PubMed Central

Goldsmith, J R; Grossman, C M; Morton, W E; Nussbaum, R H; Kordysh, E A; Quastel, M R; Sobel, R B; Nussbaum, F D

1999-01-01

We found an epidemic of juvenile hypothyroidism among a population of self-defined "downwinders" living near the Hanford nuclear facility located in southeast Washington State. The episode followed massive releases of 131I. Self-reported data on 60 cases of juvenile hypothyroidism (<20 years of age) among a group of 801 Hanford downwinders are presented, as well as data concerning the thyroid status of approximately 160,000 children exposed to radioiodine before 10 years of age as a result of the 26 April 1986 Chernobyl explosion in the former Soviet Union. These children were residents of five regions near Chernobyl. They were examined by standardized screening protocols over a period of 5 years from 1991 to 1996. They are a well-defined group of 10 samples. Fifty-six cases of hypothyroidism were found among boys and 92 among girls. Body burdens of 137Cs have been correlated with hypothyroidism prevalence rates. On the other hand, the group of juvenile (<20 years of age) Hanford downwinders is not a representative sample. Most of the 77 cases of juvenile hypothyroidism in the Hanford group were diagnosed from 1945 to 1970. However, the ratio of reported cases to the county population under 20 years of age is roughly correlated with officially estimated mean levels of cumulative thyroid 131I uptake in these counties, providing evidence that juvenile hypothyroidism was associated with radioiodine exposures. Because even subtle hypothyroidism may be of clinical significance in childhood and can be treated, it may be useful to screen for the condition in populations exposed to radioiodine fallout. Although radiation exposure is associated with hypothyroidism, its excess among fallout-exposed children has not been previously quantified. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:10090710

Dynamic PET and SPECT imaging with radioiodinated, amyloid-reactive peptide p5 in mice: A positive role for peptide dehalogenation

PubMed Central

Martin, Emily B.; Kennel, Stephen J.; Richey, Tina; Wooliver, Craig; Osborne, Dustin; Williams, Angela; Stuckey, Alan; Wall, Jonathan S.

2014-01-01

Dynamic molecular imaging provides bio-kinetic data that is used to characterize novel radiolabeled tracers for the detection of disease. Amyloidosis is a rare protein misfolding disease that can affect many organs. It is characterized by extracellular deposits composed principally of fibrillar proteins and hypersulfated proteoglycans. We have previously described a peptide, p5, which binds preferentially to amyloid deposits in a murine model of reactive (AA) amyloidosis. We have determined the whole body distribution of amyloid by molecular imaging techniques using radioiodinated p5. The loss of radioiodide from imaging probes due to enzymatic reaction has plagued the use of radioiodinated peptides and antibodies. Therefore, we studied iodine-124-labeled p5 by using dynamic PET imaging of both amyloid-laden and healthy mice to assess the rates of amyloid binding, the relevance of dehalogenation and the fate of the radiolabeled peptide. Rates of blood pool clearance, tissue accumulation and dehalogenation of the peptide were estimated from the images. Comparisons of these properties between the amyloid-laden and healthy mice provided kinetic profiles whose differences may prove to be indicative of the disease state. Additionally, we performed longitudinal SPECT/CT imaging with iodine-125-labeled p5 up to 72 hours post injection to determine the stability of the radioiodinated peptide when bound to the extracellular amyloid. Our data show that amyloid-associated peptide, in contrast to the unbound peptide, is resistant to dehalogenation resulting in enhanced amyloid-specific imaging. These data further support the utility of this peptide for detecting amyloidosis and monitoring potential therapeutic strategies in patients. PMID:25102446

Dynamic PET and SPECT imaging with radioiodinated, amyloid-reactive peptide p5 in mice: a positive role for peptide dehalogenation.

PubMed

Martin, Emily B; Kennel, Stephen J; Richey, Tina; Wooliver, Craig; Osborne, Dustin; Williams, Angela; Stuckey, Alan; Wall, Jonathan S

2014-10-01

Dynamic molecular imaging provides bio-kinetic data that is used to characterize novel radiolabeled tracers for the detection of disease. Amyloidosis is a rare protein misfolding disease that can affect many organs. It is characterized by extracellular deposits composed principally of fibrillar proteins and hypersulfated proteoglycans. We have previously described a peptide, p5, which binds preferentially to amyloid deposits in a murine model of reactive (AA) amyloidosis. We have determined the whole body distribution of amyloid by molecular imaging techniques using radioiodinated p5. The loss of radioiodide from imaging probes due to enzymatic reaction has plagued the use of radioiodinated peptides and antibodies. Therefore, we studied iodine-124-labeled p5 by using dynamic PET imaging of both amyloid-laden and healthy mice to assess the rates of amyloid binding, the relevance of dehalogenation and the fate of the radiolabeled peptide. Rates of blood pool clearance, tissue accumulation and dehalogenation of the peptide were estimated from the images. Comparisons of these properties between the amyloid-laden and healthy mice provided kinetic profiles whose differences may prove to be indicative of the disease state. Additionally, we performed longitudinal SPECT/CT imaging with iodine-125-labeled p5 up to 72h post injection to determine the stability of the radioiodinated peptide when bound to the extracellular amyloid. Our data show that amyloid-associated peptide, in contrast to the unbound peptide, is resistant to dehalogenation resulting in enhanced amyloid-specific imaging. These data further support the utility of this peptide for detecting amyloidosis and monitoring potential therapeutic strategies in patients. Copyright © 2014 Elsevier Inc. All rights reserved.

Thyroid Cysts in Cats: A Retrospective Study of 40 Cases.

PubMed

Miller, M L; Peterson, M E; Randolph, J F; Broome, M R; Norsworthy, G D; Rishniw, M

2017-05-01

Thyroid cysts are rare in cats and poorly documented. To report distinguishing clinical features and treatment responses of cats with thyroid cysts. Forty client-owned cats. Retrospective review of medical records for cats with thyroid cysts confirmed by scintigraphy, ultrasound, magnetic resonance imaging, or necropsy at 4 referral centers between 2005 and 2016. Signalment, clinical findings, diagnostic testing, treatment, and outcome were recorded. Cats ranged in age from 8 to 20 years with no apparent breed or sex predilection. 37 of 40 (93%) cats were hyperthyroid (duration, 1-96 months). Clinical findings included palpable neck mass (40/40, 100%), weight loss (15/40, 38%), dysphagia (8/40, 20%), decreased appetite (5/40, 13%), and dyspnea (4/40, 10%). Cysts were classified as small (≤8 cm 3 ) in 16 (40%) and large (>8 cm 3 ) in 24 (60%) cats. Of 25 cats treated with radioiodine, hyperthyroidism resolved in 23 (92%), whereas thyroid cysts resolved in 12 (50%). Radioiodine treatment resolved small cysts in 8 of 13 (62%) cats and large cysts in 4 of 11 (36%) cats. Eight cats, including 2 euthyroid cats, underwent thyroid-cystectomy; 3 with bilateral thyroid involvement were euthanized postoperatively for hypocalcemia. Excised cystic thyroid masses were identified as cystadenoma (4) and carcinoma (4). Thyroid cysts are encountered in hyperthyroid and euthyroid cats with benign and malignant thyroid tumors. Radioiodine treatment alone inconsistently resolved thyroid cysts. Thyroid-cystectomy could be considered in cats with unilateral thyroid disease or when symptomatic cysts persist despite successful radioiodine treatment of hyperthyroidism. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Impact of the Amount of Liquid Intake on the Dose Rate of Patients Treated with Radioiodine.

PubMed

Haghighatafshar, Mahdi; Banani, Aida; Zeinali-Rafsanjani, Banafsheh; Etemadi, Zahra; Ghaedian, Tahereh

2018-01-01

Despite therapeutic effects of radioiodine in patients with differentiated thyroid cancer, there are some disadvantages due to harmful radiation to other tissues. According to the current guidelines, patients are recommended to drink lots of water and frequent voiding to reduce the amount of 131 I in the body. This study was designed to assess the impact of the amount of liquid intake on reduction of the measured dose rate of radioiodine-treated patients. A total of 42 patients with differentiated thyroid cancer without metastasis who had undergone total thyroidectomy and had been treated with radioiodine were selected. The patients were divided into two groups according to the amount of their fluid intake which was measured during the first 48 h after 131 I administration. In all patients, the dose rate was measured immediately and 48 h after iodine administration. Each group included 21 patients. Dose rate ratio (the ratio of the second dose rate to the first dose rate) and dose rate difference ratio (the ratio of the difference between the two measured dose rates to the first dose rate) were calculated for each patient. Despite the significant difference in the amount of the liquid drunk, no statistically significant difference was seen between the different groups in parameters of dose-rate ratio and dose-rate difference ratio. Higher fluid intake (>60 ml/h in our study) alone would not effectively reduce the patient's radiation dose rate at least not more than a well-hydrated state. It seems that other interfering factors in the thyroidectomized patients may also have some impacts on this physiologic process.

(131)I treatment in Differentiated Thyroid Cancer and End-Stage Renal Disease.

PubMed

Ortega, A J M; Vázquez, R G; Cuenca, J I C; Brocca, M A M; Castilla, J; Martínez, J M M; González, E N

2016-01-01

Radioiodine (RAI) is a cornerstone in the treatment of Differentiated Thyroid Cancer (DTC). In patients on haemodialysis due to End-Stage Renal Disease (ESRD), it must be used cautiously, considering the renal clearance of this radionuclide. Also, the safety of the procedure and subsequent long-term outcome is still not well defined. In 2001, we described a dosimetric method and short-term results in three patients, with a good safety profile. We hypothesize that our method is safe in a long-term scenario without compromising the prognosis of both renal and thyroid disease. Descriptive-retrospective study. A systematic search was carried out using our clinical database from 2000 to 2014. DTC and radioiodine treatment while on haemodialysis. peritoneal dialysis. Final sample n=9 patients (n=5 males), age 48 years (median age 51 years males, 67 years female group); n=8 papillary thyroid cancer, n=1 follicular thyroid cancer; n=5 lymph node invasion; n=1 metastatic disease. Median RAI dose administered on haemodialysis 100mCi. 7.5 years after radioiodine treatment on haemodialysis, n=7 deemed free of thyroid disease, n=1 persistent non-localised disease. No complications related to the procedure or other target organs were registered. After 3.25 years, n=4 patients underwent successful renal transplantation; n=4 patients did not meet transplantation criteria due to other conditions unrelated to the thyroid disease or its treatment. One patient died due to ischemic cardiomyopathy (free of thyroid disease). Radioiodine treatment during haemodialysis is a long-term, safe procedure without worsening prognosis of either renal or thyroid disease. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Treatment of hyperthyroidism with radioiodine targeted activity: A comparison between two dosimetric methods.

PubMed

Amato, Ernesto; Campennì, Alfredo; Leotta, Salvatore; Ruggeri, Rosaria M; Baldari, Sergio

2016-06-01

Radioiodine therapy is an effective and safe treatment of hyperthyroidism due to Graves' disease, toxic adenoma, toxic multinodular goiter. We compared the outcomes of a traditional calculation method based on an analytical fit of the uptake curve and subsequent dose calculation with the MIRD approach, and an alternative computation approach based on a formulation implemented in a public-access website, searching for the best timing of radioiodine uptake measurements in pre-therapeutic dosimetry. We report about sixty-nine hyperthyroid patients that were treated after performing a pre-therapeutic dosimetry calculated by fitting a six-point uptake curve (3-168h). In order to evaluate the results of the radioiodine treatment, patients were followed up to sixty-four months after treatment (mean 47.4±16.9). Patient dosimetry was then retrospectively recalculated with the two above-mentioned methods. Several time schedules for uptake measurements were considered, with different timings and total number of points. Early time schedules, sampling uptake up to 48h, do not allow to set-up an accurate treatment plan, while schedules including the measurement at one week give significantly better results. The analytical fit procedure applied to the three-point time schedule 3(6)-24-168h gave results significantly more accurate than the website approach exploiting either the same schedule, or the single measurement at 168h. Consequently, the best strategy among the ones considered is to sample the uptake at 3(6)-24-168h, and carry out an analytical fit of the curve, while extra measurements at 48 and 72h lead only marginal improvements in the accuracy of therapeutic activity determination. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Glucose-derived AGEs promote migration and invasion of colorectal cancer by up-regulating Sp1 expression.

PubMed

Deng, Ruyuan; Wu, Huo; Ran, Hui; Kong, Xiang; Hu, Lei; Wang, Xiao; Su, Qing

2017-05-01

It is well established that the risk of colorectal cancer (CRC) is significantly increased in diabetic patients. As one of main forms of the advanced glycation end products (AGEs) that accumulate in vivo, glucose-derived AGEs play an important role in the pathogenesis of diabetic complications and may contribute to CRC progression. However, to date, both the contribution of glucose-derived AGEs to the course of CRC and the underlying mechanism are unclear. In the present study, the concentration of glucose-derived AGEs in the serum and tumor tissue of patients with CRC increased. A clinical data analysis demonstrated that the expression of the receptor for AGEs (RAGE), Specificity Protein 1 (Sp1), and matrix metallopeptidase -2 (MMP2) was significantly higher in cancerous tissues compared with non-tumor tissue in Chinese Han patients with CRC and that RAGE expression was closely associated with lymph node metastasis and TNM stage. Furthermore, in vivo and in vitro experiments showed that AGEs promoted invasion and migration of colorectal cancer, and the AGEs treatment increased the expression of RAGE, Sp1, and MMP2 in a dose-dependent manner. A RAGE blocking antibody and an Sp1-specific siRNA attenuated the AGE-induced effects. Moreover, the AGEs treatment increased the phosphorylation of ERK, and reducing the phosphorylation level of ERK by MEK1/2 inhibitor decreased the expression of Sp1. In conclusion, glucose-derived AGEs promote the invasion and metastasis of CRC partially through the RAGE/ERK/SP1/MMP2 cascade. These findings may provide an explanation for the poor prognoses of colorectal cancer in diabetic patients. Copyright © 2017 Elsevier B.V. All rights reserved.

The Path of Carbon in Photosynthesis XVIII. The Identification of Nucleotide Coenzymes

DOE R&D Accomplishments Database

Buchanan, J. G.; Lynch, V. H.; Benson, A. A.; Calvin, M.; Bradley, D. F.

1953-01-19

The radioactive compounds to be observed when algae or green leaves are allowed to photosynthesize in C{sup 14}O{sub 2} for short periods are almost all phosphorylated derivatives of sugars. Of these, phosphate esters of trioses, sedoheptulose and fructose are the first to incorporate C{sup 14} followed closely by ribulose diphosphate, glucose-6-phosphate and a phosphate of mannose. It has been noted, in earlier papers of this series, that on radiograms of the products of photosynthesis, a dark area appeared in a position occupied by no known sugar phosphate and which gave glucose on acid hydrolysis or on treatment with a phosphatase preparation. This has hitherto been referred to as an 'unknown glucose phosphate'. It was found that this substance was more labile to acid than glucose-l-phosphate, itself a readily hydrolysable phosphate, and furthermore that other labile glucose derivatives were formed as intermediates during the acid hydrolysis. Accumulation of labeled glucose in this area precedes that in sucrose and suggests its synthetic relationship to sucrose phosphate synthesis.

Review on synthesis of ferrocene-based redox polymers and derivatives and their application in glucose sensing.

PubMed

Saleem, Muhammad; Yu, Haojie; Wang, Li; Zain-ul-Abdin; Khalid, Hamad; Akram, M; Abbasi, Nasir M; Huang, Jin

2015-05-30

The interest in glucose biosensors persisted over many years and persistent efforts have been made to develop long term stable glucose biosensors with precision, smart analytical performance, good linearity and resistance to communal interferences. In this regard, ferrocene-based polymers and derivatives (FBPDs) for the development of glucose biosensor (GBs) as redox mediators have acquired utmost attention of the scientists, especially in the second generation biosensors, as a large number of innovative molecules have been synthesized. Most of the FBPDs are considered as active components in the development of GBs, due to their ease of modification, biocompatibility, stability, large surface area, good electrical conductivity and especially excellent redox properties. This review provides a brief description of synthesis, analytical performance and glucose sensing application of ferrocene-based dendrimers, polythiophenes, polypyrroles, polyethylenimine, chitosan and carbon nano tubes (CNTs). Moreover, the analytical performance of ferrocene-based glucose biosensors (FBGBs) is summarized and the problems associated with the construction of GBs and the future trends are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

In vivo cardiac glucose metabolism in the high-fat fed mouse: Comparison of euglycemic–hyperinsulinemic clamp derived measures of glucose uptake with a dynamic metabolomic flux profiling approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kowalski, Greg M., E-mail: greg.kowalski@deakin.edu.au; De Souza, David P.; Risis, Steve

Rationale: Cardiac metabolism is thought to be altered in insulin resistance and type 2 diabetes (T2D). Our understanding of the regulation of cardiac substrate metabolism and insulin sensitivity has largely been derived from ex vivo preparations which are not subject to the same metabolic regulation as in the intact heart in vivo. Studies are therefore required to examine in vivo cardiac glucose metabolism under physiologically relevant conditions. Objective: To determine the temporal pattern of the development of cardiac insulin resistance and to compare with dynamic approaches to interrogate cardiac glucose and intermediary metabolism in vivo. Methods and results: Studies were conducted to determine themore » evolution of cardiac insulin resistance in C57Bl/6 mice fed a high-fat diet (HFD) for between 1 and 16 weeks. Dynamic in vivo cardiac glucose metabolism was determined following oral administration of [U-{sup 13}C] glucose. Hearts were collected after 15 and 60 min and flux profiling was determined by measuring {sup 13}C mass isotopomers in glycolytic and tricarboxylic acid (TCA) cycle intermediates. Cardiac insulin resistance, determined by euglycemic–hyperinsulinemic clamp, was evident after 3 weeks of HFD. Despite the presence of insulin resistance, in vivo cardiac glucose metabolism following oral glucose administration was not compromised in HFD mice. This contrasts our recent findings in skeletal muscle, where TCA cycle activity was reduced in mice fed a HFD. Similar to our report in muscle, glucose derived pyruvate entry into the TCA cycle in the heart was almost exclusively via pyruvate dehydrogenase, with pyruvate carboxylase mediated anaplerosis being negligible after oral glucose administration. Conclusions: Under experimental conditions which closely mimic the postprandial state, the insulin resistant mouse heart retains the ability to stimulate glucose metabolism. - Highlights: • Insulin clamp was used to determine the evolution of cardiac insulin resistance. • Clamp measures were compared to a dynamic metabolomics approach. • The clamp revealed the presence of cardiac insulin resistance after 3 weeks of HFD. • Cardiac glucose metabolism was not affected by HFD during an oral glucose challenge.« less

Involvement of functional groups on the surface of carboxyl group-terminated polyamidoamine dendrimers bearing arbutin in inhibition of Na⁺/glucose cotransporter 1 (SGLT1)-mediated D-glucose uptake.

PubMed

Sakuma, Shinji; Kanamitsu, Shun; Teraoka, Yumi; Masaoka, Yoshie; Kataoka, Makoto; Yamashita, Shinji; Shirasaka, Yoshiyuki; Tamai, Ikumi; Muraoka, Masahiro; Nakatsuji, Yohji; Kida, Toshiyuki; Akashi, Mitsuru

2012-04-02

A carboxyl group-terminated polyamidoamine dendrimer (generation: 3.0) bearing arbutin, which is a substrate of Na⁺/glucose cotransporter 1 (SGLT1), via a nonbiodegradable ω-amino triethylene glycol linker (PAMAM-ARB), inhibits SGLT1-mediated D-glucose uptake, as does phloridzin, which is a typical SGLT1 inhibitor. Here, since our previous research revealed that the activity of arbutin was dramatically improved through conjugation with the dendrimer, we examined the involvement of functional groups on the dendrimer surface in inhibition of SGLT1-mediated D-glucose uptake. PAMAM-ARB, with a 6.25% arbutin content, inhibited in vitro D-glucose uptake most strongly; the inhibitory effect decreased as the arbutin content increased. In vitro experiments using arbutin-free original dendrimers indicated that dendrimer-derived carboxyl groups actively participated in SGLT1 inhibition. However, the inhibitory effect was much less than that of PAMAM-ARB and was equal to that of glucose moiety-free PAMAM-ARB. Data supported that the glucose moiety of arbutin was essential for the high activity of PAMAM-ARB in SGLT1 inhibition. Analysis of the balance of each domain further suggested that carboxyl groups anchored PAMAM-ARB to SGLT1, and the subsequent binding of arbutin-derived glucose moieties to the target sites on SGLT1 resulted in strong inhibition of SGLT1-mediated D-glucose uptake.

The proposed terminology 'A(1c)-derived average glucose' is inherently imprecise and should not be adopted.

PubMed

Bloomgarden, Z T; Inzucchi, S E; Karnieli, E; Le Roith, D

2008-07-01

The proposed use of a more precise standard for glycated (A(1c)) and non-glycated haemoglobin would lead to an A(1c) value, when expressed as a percentage, that is lower than that currently in use. One approach advocated to address the potential confusion that would ensue is to replace 'HbA(1c)' with a new term, 'A(1c)-derived average glucose.' We review evidence from several sources suggesting that A(1c) is, in fact, inherently imprecise as a measure of average glucose, so that the proposed terminology should not be adopted.

D-glucose derived novel gemini surfactants: synthesis and study of their surface properties, interaction with DNA, and cytotoxicity.

PubMed

Kumar, Vikash; Chatterjee, Amrita; Kumar, Nupur; Ganguly, Anasuya; Chakraborty, Indranil; Banerjee, Mainak

2014-10-09

Four new D-glucose derived m-s-m type gemini surfactants with variable spacer and tail length have been synthesized by a simple and efficient synthetic methodology utilizing the free C-3 hydroxy group of diisopropylidene glucose. The synthetic route to these gemini surfactants with a quaternary ammonium group as polar head group involves a sequence of simple reactions including alkylation, imine formation, quaternization of amine etc. The surface properties of the new geminis were evaluated by surface tension and conductivity measurements. These gemini surfactants showed low cytotoxicity by MTT assay on HeLa cell line. The DNA binding capabilities of these surfactants were determined by agarose gel electrophoresis, fluorescence titration, and DLS experiments. The preliminary studies by agarose gel electrophoresis indicated chain length dependent DNA binding abilities, further supported by ethidium bromide exclusion experiments. Two of the D-glucose derived gemini surfactants showed effective binding with pET-28a plasmid DNA (pDNA) at relatively low N/P ratio (i.e., cationic nitrogen/DNA phosphate molar ratio). Copyright © 2014 Elsevier Ltd. All rights reserved.

21 CFR 184.1318 - Glucono delta-lactone.

Code of Federal Regulations, 2014 CFR

2014-04-01

.... Gluconic acid may be produced by the oxidation of D-glucose with bromine water, by the oxidation of D... oxidation of D-glucose with enzymes derived from these microorganisms. (b) The ingredient meets the...

Preliminary crystallographic analysis of ADP-glucose pyrophosphorylase from Agrobacterium tumefaciens

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cupp-Vickery, Jill R., E-mail: jvickery@uci.edu; Igarashi, Robert Y.; Meyer, Christopher R.

2005-03-01

Crystallization and X-ray diffraction methods for native A. tumefaciens ADP-glucose pyrophosphorylase and its selenomethionyl derivative are described. Two crystal forms are identified, both of which diffract to 2 Å.

(131)I-Nimotuzumab - A potential radioimmunotherapeutic agent in treatment of tumors expressing EGFR.

PubMed

Kameswaran, Mythili; Samuel, Grace; Dev Sarma, Haladhar; Shinde, Swamirao N; Dash, Ashutosh; Venkatesh, Meera

2015-08-01

The anti-EGFR antibody Nimotuzumab was radioiodinated with I-131 by Chloramine T and Iodogen methods. The (131)I-Nimotuzumab was purified and characterized by HPLC. Purified (131)I-Nimotuzumab exhibited radiochemical purity of >95% and retained good in vitro stability upto 24h at room temperature by both the methods. Cell binding studies carried out in A431 cells expressing EGF receptors showed good immunoreactivity of the product upto 5 days post radioiodination. Biodistribution studies in normal Swiss mice showed fast clearance by both renal and gastrointestinal routes with minimal thyroid uptake. Copyright © 2015 Elsevier Ltd. All rights reserved.

From prophylaxis to atomic cocktail: circulation of radioiodine.

PubMed

Santesmases, María Jesús

2009-01-01

This paper is a history of iodine. To trace the trajectory of this element, goiter is used as a guideline for the articulation of a historical account, as a representation of thyroid disorders and of the spaces of knowledge and practices related to iodine. Iodine's journey from goiter treatment and prophylaxis in the late interwar period took on a new course after WWII by including the element's radioactive isotopes. I intend to show how the introduction of radioiodine contributed to stabilize the epistemic role of iodine, in both its non-radioactive and radioactive form, in thyroid gland studies and in the treatment of its disorders.

Lymphocyte function following radioiodine therapy in patients with thyroid carcinoma.

PubMed

Barsegian, V; Müller, S P; Horn, P A; Bockisch, A; Lindemann, M

2011-01-01

Since the nuclear disaster in Fukushima has raised great concern about the danger of radioactivity, we here addressed the question if the therapeutic use of iodine 131, the most frequently applied radionuclide, was harmful to immune function in patients. It was our aim to define for the first time in a clinical setting how radioiodine therapy alters anti-microbial immune responses. In 21 patients with thyroid carcinoma anti-microbial lymphocyte responses were assessed by lymphocyte transformation test and ELISpot - measuring lymphocyte proliferation and on a single cell level production of pro- and anti-inflammatory cytokines (interferon-γ and interleukin-10) - prior to therapy, at day 1 and day 7 post therapy. Proliferative lymphocyte responses and interferon-γ production after in vitro stimulation with microbial antigens were significantly (p < 0.05) increased at day 1 vs. pre therapy, and returned to pre therapy levels at day 7. On the contrary, at day 1 interleukin-10 production was significantly (p < 0.05) reduced. Thus, we observed a short-term increase in pro-inflammatory immune responses. However, T lymphocyte responses were in the range of healthy controls at all three time points. Thyroid carcinoma patients receiving radioiodine therapy do not display any sign of immunosuppression.

Benefits of automated surface decontamination of a radioiodine ward.

PubMed

Westcott, Eliza; Broadhurst, Alicia; Crossley, Steven; Lee, Lloyd; Phan, Xuyen; Scharli, Rainer; Xu, Yan

2012-02-01

A floor-washing robot has been acquired to assist physicists with decontamination of radioiodine therapy ward rooms after discharge of the patient at Sir Charles Gairdner Hospital. The effectiveness of the robot in decontaminating the ward has been evaluated. A controlled experiment was performed by deliberately contaminating a polyvinyl chloride flooring offcut with 131I followed by automated decontamination with the robot. The extent of fixed and removable contamination was assessed before and after decontamination by two methods: (1) direct Geiger-Mueller counting and (2) beta-counting wipe tests. Surface contamination was also assessed in situ on the ward by Geiger-Mueller counting and wipe testing. Contamination maps confirmed that contamination was removed rather than spread around by the robot. Wipe testing revealed that the robot was successful in clearing approximately 60-80% of removable contamination. The robotic floor-washing device was considered suitable to provide effective automated decontamination of the radioiodine ward. In addition, the robot affords other benefits: the time spent by the physicists decontaminating the room is greatly reduced offering financial and occupational safety and health benefits. The robot has also found utility in other decontamination applications in the healthcare environment.

Unexpected effect of furosemide on radioiodine urinary excretion in patients with differentiated thyroid carcinomas treated with iodine 131.

PubMed

Matovic, Milovan D; Jankovic, Slobodan M; Jeremic, Marija; Tasic, Zoran; Vlajkovic, Marina

2009-08-01

In patients receiving (131)I for therapeutic purposes, diuretics are frequently used in an attempt to accelerate elimination of unbound radioiodine, reduce its adverse effects, and shorten the hospital stay. The aims of our study were to investigate the influence of furosemide therapy on urinary excretion of (131)I in patients with differentiated thyroid cancer (DTC), referred to radioiodine ablation after thyroidectomy, and to investigate whether diuretics are useful in daily practice in patients with DTC. Forty-three patients with DTC who had normal renal function and low (131)I uptake in cervical region (3.55 +/- 3.45%) were included in this study. The furosemide (20 mg) and potassium chloride (250 mg) were given orally to 23 patients 3 hours after the (131)I administration, and then q8h for 3 days. Twenty patients did not receive either furosemide or potassium chloride. After (131)I administration, the patients collected their urine for 3 days, and radioactivity of urine sample from each micturition was expressed as percentage of the administered dose. Radioactivity of blood samples was measured after 72 hours, and the values were corrected for decay of (131)I and expressed in relation to the administered dose. Initial whole-body measurement (immediately after (131)I administration) and the whole-body measurement after 72 hours were recorded for all patients. The 72-hour whole-body measurement was corrected for decay of (131)I, and expressed as a percentage of the initial whole-body measurement. Urinary excretion of (131)I was significantly lower in the patients who were taking furosemide and potassium chloride compared with the control group. The whole-body measurements after 72 hours (13.22 +/- 6.55% vs. 8.24 +/- 3.39% of the initial; p < 0.01, respectively) and the blood radioactivity (34.66 +/- 24.84 vs. 11.64 +/- 8.32 cpm/mL per 1 MBq of administered (131)I, p < 0.01) were found to be unexpectedly higher in the patients who were taking furosemide and potassium chloride compared with the control group. Our results demonstrated that furosemide given as an adjuvant medication in patients with DTC causes a significant decrease in urinary excretion of radioiodine and its higher blood concentration. Therefore, furosemide should not be recommended as an adjuvant therapy to radioiodine ablation in patients with DTC previously iodine depleted by low-iodine diet.

Comparison of mortality in hyperthyroidism during periods of treatment with thionamides and after radioiodine.

PubMed

Boelaert, Kristien; Maisonneuve, Patrick; Torlinska, Barbara; Franklyn, Jayne A

2013-05-01

Hyperthyroidism is common, but opinions regarding optimal therapy with antithyroid drugs or radioiodine (131-I) differ. There are no randomized trials comparing these options in terms of mortality. The aim of the study was to determine whether mortality associated with hyperthyroidism varies with treatment administered or other factors. We conducted a prospective observational population-based study of 1036 subjects aged ≥ 40 years presenting to a single specialist clinic from 1989-2003 with a first episode of hyperthyroidism who were followed until June 2012. Antithyroid drugs or radioiodine (131-I) were administered. We compared causes of death with age-, sex-, and period-specific mortality in England and Wales and used within-cohort analysis of influence of treatment modality, outcome, disease etiology, severity and control, and comorbidities. In 12 868 person-years of follow-up, 334 died vs 290.6 expected (standardized mortality ratio [SMR], 1.15 [95% confidence interval (CI),1.03-1.28]; P = .01). Increased all-cause mortality largely reflected increased circulatory deaths (SMR, 1.20 [95% CI, 1.01-1.43]; P = .04). All-cause mortality was increased for the person-years accumulated during thionamide treatment (SMR, 1.30 [95% CI, 1.05-1.61]; P = .02) and after 131-I not associated with hypothyroidism (SMR, 1.24 [95% CI, 1.04-1.46]; P = .01) but not during T₄ replacement for 131-I-induced hypothyroidism (SMR, 0.98 [95% CI, 0.82-1.18]; P = .85). Within-cohort analysis comparing mortality during thionamide treatment showed a similar hazard ratio (HR) for all-cause mortality when 131-I did not result in hypothyroidism (HR, 0.95 [95% CI, 0.70-1.29]), but reduced mortality with 131-I-induced hypothyroidism (HR, 0.70 [95% CI, 0.51-0.96]). Reduced mortality associated with hypothyroidism was seen only in those without significant comorbidities and not in those with other serious diseases. Atrial fibrillation at presentation (P = .02) and an increment of 10 pmol/L in serial free T₄ concentration during follow-up (P = .009) were independently associated with mortality. Among hyperthyroid subjects aged 40 years or older, mortality was increased during periods of thionamide treatment and after radioiodine not resulting in hypothyroidism, but not during follow-up after radioiodine-induced hypothyroidism. Independent associations of mortality with atrial fibrillation and incomplete biochemical control during treatment indicate potential causative links with poor outcome.

Neuronal glucose metabolism is impaired while astrocytic TCA cycling is unaffected at symptomatic stages in the hSOD1G93A mouse model of amyotrophic lateral sclerosis.

PubMed

Tefera, Tesfaye W; Borges, Karin

2018-01-01

Although alterations in energy metabolism are known in ALS, the specific mechanisms leading to energy deficit are not understood. We measured metabolite levels derived from injected [1- 13 C]glucose and [1,2- 13 C]acetate (i.p.) in cerebral cortex and spinal cord extracts of wild type and hSOD1 G93A mice at onset and mid disease stages using high-pressure liquid chromatography, 1 H and 13 C nuclear magnetic resonance spectroscopy. Levels of spinal and cortical CNS total lactate, [3- 13 C]lactate, total alanine and [3- 13 C]alanine, but not cortical glucose and [1- 13 C]glucose, were reduced mostly at mid stage indicating impaired glycolysis. The [1- 13 C]glucose-derived [4- 13 C]glutamate, [4- 13 C]glutamine and [2- 13 C]GABA amounts were diminished at mid stage in cortex and both time points in spinal cord, suggesting decreased [3- 13 C]pyruvate entry into the TCA cycle. Lack of changes in [1,2- 13 C]acetate-derived [4,5- 13 C]glutamate, [4,5- 13 C]glutamine and [1,2- 13 C]GABA levels indicate unchanged astrocytic 13 C-acetate metabolism. Reduced levels of leucine, isoleucine and valine in CNS suggest compensatory breakdown to refill TCA cycle intermediate levels. Unlabelled, [2- 13 C] and [4- 13 C]GABA concentrations were decreased in spinal cord indicating that impaired glucose metabolism contributes to hyperexcitability and supporting the use of treatments which increase GABA amounts. In conclusion, CNS glucose metabolism is compromised, while astrocytic TCA cycling appears to be normal in the hSOD1 G93A mouse model at symptomatic disease stages.

Probing the metabolic network in bloodstream-form Trypanosoma brucei using untargeted metabolomics with stable isotope labelled glucose.

PubMed

Creek, Darren J; Mazet, Muriel; Achcar, Fiona; Anderson, Jana; Kim, Dong-Hyun; Kamour, Ruwida; Morand, Pauline; Millerioux, Yoann; Biran, Marc; Kerkhoven, Eduard J; Chokkathukalam, Achuthanunni; Weidt, Stefan K; Burgess, Karl E V; Breitling, Rainer; Watson, David G; Bringaud, Frédéric; Barrett, Michael P

2015-03-01

Metabolomics coupled with heavy-atom isotope-labelled glucose has been used to probe the metabolic pathways active in cultured bloodstream form trypomastigotes of Trypanosoma brucei, a parasite responsible for human African trypanosomiasis. Glucose enters many branches of metabolism beyond glycolysis, which has been widely held to be the sole route of glucose metabolism. Whilst pyruvate is the major end-product of glucose catabolism, its transamination product, alanine, is also produced in significant quantities. The oxidative branch of the pentose phosphate pathway is operative, although the non-oxidative branch is not. Ribose 5-phosphate generated through this pathway distributes widely into nucleotide synthesis and other branches of metabolism. Acetate, derived from glucose, is found associated with a range of acetylated amino acids and, to a lesser extent, fatty acids; while labelled glycerol is found in many glycerophospholipids. Glucose also enters inositol and several sugar nucleotides that serve as precursors to macromolecule biosynthesis. Although a Krebs cycle is not operative, malate, fumarate and succinate, primarily labelled in three carbons, were present, indicating an origin from phosphoenolpyruvate via oxaloacetate. Interestingly, the enzyme responsible for conversion of phosphoenolpyruvate to oxaloacetate, phosphoenolpyruvate carboxykinase, was shown to be essential to the bloodstream form trypanosomes, as demonstrated by the lethal phenotype induced by RNAi-mediated downregulation of its expression. In addition, glucose derivatives enter pyrimidine biosynthesis via oxaloacetate as a precursor to aspartate and orotate.

A novel thiamine-derived pigment, pyrizepine, formed by the Maillard reaction.

PubMed

Igoshi, Asuka; Noda, Kyoko; Murata, Masatsune

2018-04-26

To find a Maillard pigment derived from thiamine, a solution containing glucose and thiamine was heated and analyzed with high-performance liquid chromatography equipped with diode-array detection. As a result, a unique peak showing an absorption maximum at 380 nm was detected. This peak was then isolated from a reaction solution containing glucose, lysine and thiamine, and was identified as 1-(2-methyl-6,9-dihydro-5H-pyrimido[4,5-e][1,4]diazepin-7-yl)ethan-1-one using instrumental analyses. This compound, named pyrizepine, was a novel yellow pigment having a fused ring consisting of pyrimidine and diazepine. Pyrizepine was a major low-molecular-weight pigment in the reaction solution. The structure suggests that pyrizepine is formed by condensation reaction between a degradation product of thiamine and a tetrosone derivative formed from glucose by the Maillard reaction.

N-hydroxycinnamide derivatives of osthole ameliorate hyperglycemia through activation of AMPK and p38 MAPK.

PubMed

Lee, Wei-Hwa; Wu, Hsueh-Hsia; Huang, Wei-Jan; Li, Yi-Ning; Lin, Ren-Jye; Lin, Shyr-Yi; Liang, Yu-Chih

2015-03-11

Our previous studies found that osthole markedly reduced blood glucose levels in both db/db and ob/ob mice. To improve the antidiabetic activity of osthole, a series of N-hydroxycinnamide derivatives of osthole were synthesized, and their hypoglycemia activities were examined in vitro and in vivo. Both N-hydroxycinnamide derivatives of osthole, OHC-4p and OHC-2m, had the greatest potential for activating AMPK and increasing glucose uptake by L6 skeletal muscle cells. In addition, OHC-4p and OHC-2m time- and dose-dependently increased phosphorylation levels of AMPK and p38 MAPK. The AMPK inhibitor, compound C, and the p38 MAPK inhibitor, SB203580, significantly reversed activation of AMPK and p38 MAPK, respectively, in OHC-4p- and OHC-2m-treated cells. Compound C and SB203580 also inhibited glucose uptake induced by OHC-4p and OHC-2m. Next, we found that OHC-4p and OHC-2m significantly increased glucose transporter 4 (GLUT4) translocation to plasma membranes and counteracted hyperglycemia in mice with streptozotocin-induced diabetes. These results suggest that activation of AMPK and p38 MAPK by OHC-4p and OHC-2m is associated with increased glucose uptake and GLUT4 translocation and subsequently led to amelioration of hyperglycemia. Therefore, OHC-4p and OHC-2m might have potential as antidiabetic agents for treating type 2 diabetes. Our previous studies found that osthole markedly reduced blood glucose levels in both db/db and ob/ob mice. To improve the antidiabetic activity of osthole, a series of N-hydroxycinnamide derivatives of osthole were synthesized, and their hypoglycemia activities were examined in vitro and in vivo. Both N-hydroxycinnamide derivatives of osthole, OHC-4p and OHC-2m, had the greatest potential for activating AMPK and increasing glucose uptake by L6 skeletal muscle cells. In addition, OHC-4p and OHC-2m time- and dose-dependently increased phosphorylation levels of AMPK and p38 MAPK. The AMPK inhibitor, compound C, and the p38 MAPK inhibitor, SB203580, significantly reversed activation of AMPK and p38 MAPK, respectively, in OHC-4p- and OHC-2m-treated cells. Compound C and SB203580 also inhibited glucose uptake induced by OHC-4p and OHC-2m. Next, we found that OHC-4p and OHC-2m significantly increased glucose transporter 4 (GLUT4) translocation to plasma membranes and counteracted hyperglycemia in mice with streptozotocin-induced diabetes. These results suggest that activation of AMPK and p38 MAPK by OHC-4p and OHC-2m is associated with increased glucose uptake and GLUT4 translocation and subsequently led to amelioration of hyperglycemia. Therefore, OHC-4p and OHC-2m might have potential as antidiabetic agents for treating type 2 diabetes.

Protective/restorative Role of the Adipose Tissue-derived Mesenchymal Stem Cells on the Radioiodine-induced Salivary Gland Damage in Rats

PubMed Central

Saylam, Güleser; Bayır, Ömer; Pınarlı, Ferda Alparslan; Han, Ünsal; Korkmaz, Mehmet Hakan; Sancaktar, Mehmet Eser; Tatar, İlkan; Sargon, Mustafa Fevzi; Tatar, Emel Çadallı

2017-01-01

Abstract Background To analyze protective/regenerative effects of adipose tissue-derived mesenchymal stem cells (ADMSC) on 131I-Radioiodine (RAI)-induced salivary gland damage in rats. Materials and Methods Study population consisted of controls (n:6) and study groups (n:54): RAI (Group 1), ADMSC (Group 2), amifostine (Group 3), RAI+amifostine (Group 4), concomitant RAI+ADMSC (Group 5) and RAI+ADMSC after 48 h (Group 6). We used light microscopy (LM), transmission electron microscopy (TEM), and salivary gland scintigraphy (SGS), and analyzed data statistically. Results We observed the homing of ADMSC in salivary glands at 1st month on LM. RAI exposure affected necrosis, periductal fibrosis, periductal sclerosis, vascular sclerosis and the total sum score were in a statistically significant manner (P < 0.05). Intragroup comparisons with LM at 1st and 6th months revealed statistically significant improvements in Group 6 (P < 0.05) but not in Groups 4 and 5. Intergroup comparisons of the total score showed that Groups 4 and 5 in 1st month and Group 6 in 6th month had the lowest values. TEM showed vacuolization, edema, and fibrosis at 1st month, and an improvement in damage in 6th month in Groups 5 and 6. SGSs revealed significant differences for the maximum secretion ratio (Smax) (P = 0.01) and the gland-to-background ratio at a maximum count (G/BGmax) (P = 0. 01) at 1st month, for G/BGmax (P = 0.01), Smax (P = 0.01) and the time to reach the maximum count ratio over the time to reach the minimum count (Tmax/Tmin) (P = 0.03) at 6th month. 1st and 6th month scans showed differences for Smax and G/BGmax (P = 0.04), but not for Tmax/Tmin (p > 0.05). We observed a significant deterioration in gland function in group 1, whereas, mild to moderate deteriorations were seen in protective treatment groups. Conclusions Our results indicated that ADMSC might play a promising role as a protective/regenerative agent against RAI-induced salivary gland dysfunction. PMID:28959167

Reduction in ins-7 gene expression in non-neuronal cells of high glucose exposed Caenorhabditis elegans protects from reactive metabolites, preserves neuronal structure and head motility, and prolongs lifespan.

PubMed

Mendler, Michael; Riedinger, Christin; Schlotterer, Andrea; Volk, Nadine; Fleming, Thomas; Herzig, Stephan; Nawroth, Peter P; Morcos, Michael

2017-02-01

Glucose derived metabolism generates reactive metabolites affecting the neuronal system and lifespan in C. elegans. Here, the role of the insulin homologue ins-7 and its downstream effectors in the generation of high glucose induced neuronal damage and shortening of lifespan was studied. In C. elegans high glucose conditions induced the expression of the insulin homologue ins-7. Abrogating ins-7 under high glucose conditions in non-neuronal cells decreased reactive oxygen species (ROS)-formation and accumulation of methylglyoxal derived advanced glycation endproducts (AGEs), prevented structural neuronal damage and normalised head motility and lifespan. The restoration of lifespan by decreased ins-7 expression was dependent on the concerted action of sod-3 and glod-4 coding for the homologues of iron-manganese superoxide dismutase and glyoxalase 1, respectively. Under high glucose conditions mitochondria-mediated oxidative stress and glycation are downstream targets of ins-7. This impairs the neuronal system and longevity via a non-neuronal/neuronal crosstalk by affecting sod-3 and glod-4, thus giving further insight into the pathophysiology of diabetic complications. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of PD/PID controller for insulin control on blood glucose regulation in a Type-I diabetes

NASA Astrophysics Data System (ADS)

Mahmud, Farhanahani; Isse, Nadir Hussien; Daud, Nur Atikah Mohd; Morsin, Marlia

2017-01-01

This project introduces a simulation of Proportional-Derivative (PD) and Proportional-Integral-Derivative (PID) controller based on a virtual Type 1 Diabetes Mellitus (T1DM) patient: Hovorka diabetic model using MATLAB-Simulink software. The results of these simulations are based on three tuning responses for each controller which are fast, slow and oscillation responses. The main purpose of this simulation is to achieve an acceptable stability and fastness response towards the regulation of glucose concentration using PD and PID controller response with insulin infusion rate. Therefore, in order to analyze and compare the responses of both controller performances, one-day simulations of the insulin-glucose dynamic have been conducted using a typical day meal plan that contains five meals of different bolus size. It is found that the PID closed-loop control with a short rise time is required to retrieve a satisfactory glucose regulation.

Clinical trials of the prototype Rutherford Appleton Laboratory MWPC positron camera at the Royal Marsden Hospital

NASA Astrophysics Data System (ADS)

Flower, M. A.; Ott, R. J.; Webb, S.; Leach, M. O.; Marsden, P. K.; Clack, R.; Khan, O.; Batty, V.; McCready, V. R.; Bateman, J. E.

1988-06-01

Two clinical trials of the prototype RAL multiwire proportional chamber (MWPC) positron camera were carried out prior to the development of a clinical system with large-area detectors. During the first clinical trial, the patient studies included skeletal imaging using 18F, imaging of brain glucose metabolism using 18F FDG, bone marrow imaging using 52Fe citrate and thyroid imaging with Na 124I. Longitudinal tomograms were produced from the limited-angle data acquisition from the static detectors. During the second clinical trial, transaxial, coronal and sagittal images were produced from the multiview data acquisition. A more detailed thyroid study was performed in which the volume of the functioning thyroid tissue was obtained from the 3D PET image and this volume was used in estimating the radiation dose achieved during radioiodine therapy of patients with thyrotoxicosis. Despite the small field of view of the prototype camera, and the use of smaller than usual amounts of activity administered, the PET images were in most cases comparable with, and in a few cases visually better than, the equivalent planar view using a state-of-the-art gamma camera with a large field of view and routine radiopharmaceuticals.

SPECT/CT demonstrating 131I retention in Warthin tumor on thyroid cancer survey scan.

PubMed

Zhang, Yuyang; Minoshima, Satoshi

2013-09-01

A 48-year-old male patient of papillary thyroid cancer, status post-thyroidectomy and node dissection, was referred to (131)I scan prior to radioiodine treatment. The images showed 1 additional focus of (131)I uptake in the right upper neck outside of the thyroid bed. SPECT/CT demonstrated 2 separate foci of radioiodine uptake in the right parotid gland, instead of neck lymph nodes. Diagnostic CT showed 2 corresponding soft tissue nodules in the right parotid gland which were confirmed latter by fine-needle aspiration to be Warthin tumors. This case illustrates a pivotal role of SPECT/CT in differential diagnosis of abnormal neck uptake on (131)I thyroid cancer scan.

Whole-body scintigraphy with radioiodine-131. A comprehensive list of false-positives with some examples.

PubMed

McDougall, I R

1995-10-01

Whole-body scintigraphy with radioiodine-131 is an important diagnostic test in the management of patients with differentiated thyroid cancer who have undergone surgical treatment. The scan can demonstrate the presence of residual thyroid or functioning metastases in lymph nodes or distant sites. However, there are a number of potential pitfalls in the interpretation of this scan that could lead to a false-positive diagnosis of cancer. The scintiscans are presented for five patients in whom uptake outside of the thyroid was not due to functioning metastases. Some of these abnormalities are physiologic, such as uptake of iodine in the gastrointestinal tract. A comprehensive list of false-positive results are tabulated.

Improved radioimmunotherapy of hematologic malignancies. Final technical report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Press, O.W.

1996-08-15

Experiments were performed to study the rates of endocytosis, intracellular routing, and metabolic degradation of radiolabeled monoclonal antibodies targeting tumor-associated antigens on human leukemia and lymphoma cells. An attempt was made to examine in vivo the effects of lysosomotropic amines and thioamides on the retention of radiolabeled monoclonal antibodies by tumor cells. Experiments also examined the impact of newer radioiodination techniques on the metabolic degradation of radioiodinated antibodies, and on the radioimmunoscintigraphy and radioimmunotherapy of neoplasms. The endocytosis, intracellular routing, and degradation of radioimmunoconjugates prepared with I-131, In-111, and Y-90 were compared. The utility of radioimmunoconjugates targeting oncogene products formore » the radioimmunotherapy and radioimmunoscintigraphy of cancer was investigated.« less

Physical characteristics of the gonadotropin receptor-hormone complexes formed in vivo and in vitro.

PubMed Central

Dufau, M L; Podesta, E J; Catt, K J

1975-01-01

The physical properties of detergent-solubilized gonadotropin receptor-hormone complexes, determined by density gradient centrifugation and gel filtration, were compared after in vivo and in vitro labeling of specific ovarian binding sites with radioiodinated human chorionic gonadotropin (hCG). Following intravenous administration of biologically active 125I-labeled hCG, up to 50% of the gonadotropin tracer was bound to the luteinized ovaries of immature female rats treated with pregnant mare serum/human chorionic gonadotropin. Comparable binding of 125I-labeled hCG was observed after equilibration of ovarian particles with the labeled hormone in vitro. The sedimentation properties of the solubilized receptor-hormone complexes formed in vivo were identical with those derived for the corresponding complexes formed in vitro and extracted with Triton X-100 and Lubrol PX, with sedimentation constants of 8.8 S for the Triton-solubilized complex and 7.0 S for the complex extracted with Lubrol PX. During analytical gel filtration of the Triton-solubilized receptor-hormone complex on Sepharose 6B in 0.1% Triton X-100, the partition coefficient (Kav) of the "in vivo" complex (0.32) was not significantly different from that of the complex formed in vitro (0.29). Gel filtration of the Lubrol-solubilized ovarian particles on Sepharose 6B in 0.5% Lubrol PX gave Kav values for the "in vivo" and "in vitro" labeled complexes of 0.36 and 0.32, respectively. These findings demonstrate that the physical properties of size and shape which determine the partition coefficient and sedimentation characteristics of detergent-solubilized gonadotropin receptor-hormone complexes formed in vitro are not distinguishable from those of the complexes extracted after specific interaction of the ovarian gonadotropin receptors with radioiodinated hCG in vivo. PMID:165502

A closed-loop artificial pancreas using a proportional integral derivative with double phase lead controller based on a new nonlinear model of glucose metabolism.

PubMed

Abbes, Ilham Ben; Richard, Pierre-Yves; Lefebvre, Marie-Anne; Guilhem, Isabelle; Poirier, Jean-Yves

2013-05-01

Most closed-loop insulin delivery systems rely on model-based controllers to control the blood glucose (BG) level. Simple models of glucose metabolism, which allow easy design of the control law, are limited in their parametric identification from raw data. New control models and controllers issued from them are needed. A proportional integral derivative with double phase lead controller was proposed. Its design was based on a linearization of a new nonlinear control model of the glucose-insulin system in type 1 diabetes mellitus (T1DM) patients validated with the University of Virginia/Padova T1DM metabolic simulator. A 36 h scenario, including six unannounced meals, was tested in nine virtual adults. A previous trial database has been used to compare the performance of our controller with their previous results. The scenario was repeated 25 times for each adult in order to take continuous glucose monitoring noise into account. The primary outcome was the time BG levels were in target (70-180 mg/dl). Blood glucose values were in the target range for 77% of the time and below 50 mg/dl and above 250 mg/dl for 0.8% and 0.3% of the time, respectively. The low blood glucose index and high blood glucose index were 1.65 and 3.33, respectively. The linear controller presented, based on the linearization of a new easily identifiable nonlinear model, achieves good glucose control with low exposure to hypoglycemia and hyperglycemia. © 2013 Diabetes Technology Society.

Inconsistent formation and nonfunction of insulin-positive cells from pancreatic endoderm derived from human embryonic stem cells in athymic nude rats.

PubMed

Matveyenko, Aleksey V; Georgia, Senta; Bhushan, Anil; Butler, Peter C

2010-11-01

Embryonic stem cell therapy has been proposed as a therapeutic strategy to restore β-cell mass and function in T1DM. Recently, a group from Novocell (now ViaCyte) reported successful development of glucose-responsive islet-like structures after implantation of pancreatic endoderm (PE) derived from human embryonic stem cells (hESC) into immune-deficient mice. Our objective was to determine whether implantation of hESC-derived pancreatic endoderm from Novocell into athymic nude rats results in development of viable glucose-responsive pancreatic endocrine tissue. Athymic nude rats were implanted with PE derived from hESC either via implantation into the epididymal fat pads or by subcutaneous implantation into TheraCyte encapsulation devices for 20 wk. Blood glucose, weight, and human insulin/C-peptide secretion were monitored by weekly blood draws. Graft β-cell function was assessed by a glucose tolerance test, and graft morphology was assessed by immunohistochemistry and immunofluorescence. At 20 wk postimplantation, epididymal fat-implanted PE progressed to develop islet-like structures in 50% of implants, with a mean β-cell fractional area of 0.8 ± 0.3%. Human C-peptide and insulin were detectable, but at very low levels (C-peptide = 50 ± 26 pmol/l and insulin = 15 ± 7 pmol/l); however, there was no increase in human C-peptide/insulin levels after glucose challenge. There was no development of viable pancreatic tissue or meaningful secretory function when human PE was implanted in the TheraCyte encapsulation devices. These data confirm that islet-like structures develop from hESC differentiated to PE by the protocol developed by NovoCell. However, the extent of endocrine cell formation and secretory function is not yet sufficient to be clinically relevant.

Inconsistent formation and nonfunction of insulin-positive cells from pancreatic endoderm derived from human embryonic stem cells in athymic nude rats

PubMed Central

Matveyenko, Aleksey V.; Georgia, Senta; Bhushan, Anil

2010-01-01

Embryonic stem cell therapy has been proposed as a therapeutic strategy to restore β-cell mass and function in T1DM. Recently, a group from Novocell (now ViaCyte) reported successful development of glucose-responsive islet-like structures after implantation of pancreatic endoderm (PE) derived from human embryonic stem cells (hESC) into immune-deficient mice. Our objective was to determine whether implantation of hESC-derived pancreatic endoderm from Novocell into athymic nude rats results in development of viable glucose-responsive pancreatic endocrine tissue. Athymic nude rats were implanted with PE derived from hESC either via implantation into the epididymal fat pads or by subcutaneous implantation into TheraCyte encapsulation devices for 20 wk. Blood glucose, weight, and human insulin/C-peptide secretion were monitored by weekly blood draws. Graft β-cell function was assessed by a glucose tolerance test, and graft morphology was assessed by immunohistochemistry and immunofluorescence. At 20 wk postimplantation, epididymal fat-implanted PE progressed to develop islet-like structures in 50% of implants, with a mean β-cell fractional area of 0.8 ± 0.3%. Human C-peptide and insulin were detectable, but at very low levels (C-peptide = 50 ± 26 pmol/l and insulin = 15 ± 7 pmol/l); however, there was no increase in human C-peptide/insulin levels after glucose challenge. There was no development of viable pancreatic tissue or meaningful secretory function when human PE was implanted in the TheraCyte encapsulation devices. These data confirm that islet-like structures develop from hESC differentiated to PE by the protocol developed by NovoCell. However, the extent of endocrine cell formation and secretory function is not yet sufficient to be clinically relevant. PMID:20587750

Effects of pentylenetetrazole and glutamate on metabolism of [U-(13)C]glucose in cultured cerebellar granule neurons.

PubMed

Eloqayli, Haytham; Qu, Hong; Unsgård, Geirmund; Sletvold, Olav; Hadidi, Hakam; Sonnewald, Ursula

2002-02-01

This study was performed to analyze the effects of glutamate and the epileptogenic agent pentylenetetrazole (PTZ) on neuronal glucose metabolism. Cerebellar granule neurons were incubated for 2 h in medium containing 3 mM [U-(13)C]glucose, with and without 0.25 mM glutamate and/or 10 mM PTZ. In the presence of PTZ, decreased glucose consumption with unchanged lactate release was observed, indicating decreased glucose oxidation. PTZ also slowed down tricarboxylic acid (TCA) cycle activity as evidenced by the decreased amounts of labeled aspartate and [1,2-(13)C]glutamate. When glutamate was present, glucose consumption was also decreased. However, the amount of glutamate, derived from [U-(13)C]glucose via the first turn of the TCA cycle, was increased. The decreased amount of [1,2-(13)C]glutamate, derived from the second turn in the TCA cycle, and increased amount of aspartate indicated the dilution of label due to the entrance of unlabeled glutamate into TCA cycle. In the presence of glutamate plus PTZ, the effect of PTZ was enhanced by glutamate. Labeled alanine was detected only in the presence of glutamate plus PTZ, which indicated that oxaloacetate was a better amino acid acceptor than pyruvate. Furthermore, there was also evidence for intracellular compartmentation of oxaloacetate metabolism. Glutamate and PTZ caused similar metabolic changes, however, via different mechanisms. Glutamate substituted for glucose as energy substrate in the TCA cycle, whereas, PTZ appeared to decrease mitochondrial activity.

Carbon Source Requirements for Exopolysaccharide Production by Lactobacillus casei CG11 and Partial Structure Analysis of the Polymer

PubMed Central

Cerning, J.; Renard, C. M. G. C.; Thibault, J. F.; Bouillanne, C.; Landon, M.; Desmazeaud, M.; Topisirovic, L.

1994-01-01

Exopolysaccharide production by Lactobacillus casei CG11 was studied in basal minimum medium containing various carbon sources (galactose, glucose, lactose, sucrose, maltose, melibiose) at concentrations of 2, 5, 10, and 20 g/liter. L. casei CG11 produced exopolysaccharides in basal minimum medium containing each of the sugars tested; lactose and galactose were the poorest carbon sources, and glucose was by far the most efficient carbon source. Sugar concentrations had a marked effect on polymer yield. Plasmid-cured Muc- derivatives grew better in the presence of glucose and attained slightly higher populations than the wild-type strain. The values obtained with lactose were considerably lower for both growth and exopolysaccharide yield. The level of specific polymer production per cell obtained with glucose was distinctively lower for Muc- derivatives than for the Muc+ strain. The polymer produced by L. casei CG11 in the presence of glucose was different from that formed in the presence of lactose. The polysaccharide produced by L. casei CG11 in basal minimum medium containing 20 g of glucose per liter had an intrinsic viscosity of 1.13 dl/g. It was rich in glucose (76%), which was present mostly as 2- or 3-linked residues along with some 2,3 doubly substituted glucose units, and in rhamnose (21%), which was present as 2-linked or terminal rhamnose; traces of mannose and galactose were also present. PMID:16349427

Effects of D-glucose upon D-fructose metabolism in rat hepatocytes: A 13C NMR study.

PubMed

Malaisse, W J; Ladrière, L; Verbruggen, I; Willem, R

2002-12-01

Isolated hepatocytes from fed rats were exposed for 120 min to D-glucose (10 mM) and either D-[1-13C]fructose, D-[2-13C]fructose or D-[6-13C]fructose (also 10 mM) in the presence of D2O. The identification and quantification of 13C-enriched D-fructose and its metabolites (D-glucose, L-lactate, L-alanine) in the incubation medium and the measurement of their deuterated isotopomers indicated, by comparison with a prior study conducted in the absence of exogenous D-glucose, that the major effects of the aldohexose were to increase the recovery of 13C-enriched D-fructose, decrease the production of 13C-enriched D-glucose, restrict the deuteration of the 13C-enriched isotopomers of D-glucose to those generated by cells exposed to D-[2-13C]fructose, and to accentuate the lesser deuteration of the C, (as compared to C5) of 13C-enriched D-glucose derived from D-[2-13C]fructose. The ratio between C2-deuterated and C2-hydrogenated L-lactate, as well as the relative amounts of the CH3-, CH2D-, CHD, and CD3- isotopomers of 13C-enriched L-lactate were not significantly different, however, in the absence or presence of exogenous D-glucose. These findings indicate that exogenous D-glucose suppressed the deuteration of the C1 of D-[I-13C]glucose generated by hepatocytes exposed to D-[1-13C]fructose or D-[6-13C]fructose, as otherwise attributable, in part at least, to gluconeogenesis from fructose-derived [3-13C]pyruvate, and apparently favoured the phosphorylation of D-fructose by hexokinase isoenzymes, probably through stimulation of D-fructose phosphorylation by glucokinase.

Absorption of Radionuclides from the Fukushima Nuclear Accident by a Novel Algal Strain

PubMed Central

Shimura, Hiroki; Itoh, Katsuhiko; Sugiyama, Atsushi; Ichijo, Sayaka; Ichijo, Masashi; Furuya, Fumihiko; Nakamura, Yuji; Kitahara, Ken; Kobayashi, Kazuhiko; Yukawa, Yasuhiro; Kobayashi, Tetsuro

2012-01-01

Large quantities of radionuclides have leaked from the Fukushima Daiichi Nuclear Power Plant into the surrounding environment. Effective prevention of health hazards resulting from radiation exposure will require the development of efficient and economical methods for decontaminating radioactive wastewater and aquatic ecosystems. Here we describe the accumulation of water-soluble radionuclides released by nuclear reactors by a novel strain of alga. The newly discovered green microalgae, Parachlorella sp. binos (Binos) has a thick alginate-containing extracellular matrix and abundant chloroplasts. When this strain was cultured with radioiodine, a light-dependent uptake of radioiodine was observed. In dark conditions, radioiodine uptake was induced by addition of hydrogen superoxide. High-resolution secondary ion mass spectrometry (SIMS) showed a localization of accumulated iodine in the cytosol. This alga also exhibited highly efficient incorporation of the radioactive isotopes strontium and cesium in a light-independent manner. SIMS analysis showed that strontium was distributed in the extracellular matrix of Binos. Finally we also showed the ability of this strain to accumulate radioactive nuclides from water and soil samples collected from a heavily contaminated area in Fukushima. Our results demonstrate that Binos could be applied to the decontamination of iodine, strontium and cesium radioisotopes, which are most commonly encountered after nuclear reactor accidents. PMID:22984475

Survival outcome of radioiodine therapy in post thyroidectomy thyroid carcinoma patients: Outcome of long term follow up

NASA Astrophysics Data System (ADS)

Haque, F.; Nahar, N.; Sultana, S.; Nasreen, F.; Jabin, Z.; Alam, A. S. M. M.

2016-03-01

The overall prognosis of patients with thyroid carcinoma is excellent whenever managed following best practice guidelines. Objective: To calculate sex and age group affected by thyroid cancer; to compare between single or multiple dose of radio ablation needed after thyroidectomy and to determine the percentage of patients become disease free during their follow up. Methods: This was a retrospective study done in NINMAS, Bangladesh on 687 patients from 1984 to 2004. In all cases total or near total thyroidectomy was done before commencing radioiodine therapy. Patients TG level, neck ultrasonography, thyroid scan, whole body I131 scans, neck examination were done every six monthly/yearly. Results: Among 687 patients, female were more sufferers (68.1%) and female to male ratio was 2:1. Age group 19-40 years was mostly affected (57.8%). Most common type seen was papillary carcinoma (81.8%). After ablation 100 patients did not follow-up. Total 237 patients discontinued within 4 years. Remaining 450 patients undergone regular follow-up for 5 years and more, 394 were disease free (87.6%). Total recurrence of metastasis was 23 and 12 patients expired at different times. Conclusions: Long-term regular follow-up is necessary after radioiodine ablation to become free of disease.

Methylglyoxal and carboxyethyllysine reduce glutamate uptake and S100B secretion in the hippocampus independently of RAGE activation.

PubMed

Hansen, Fernanda; Battú, Cíntia Eickhoff; Dutra, Márcio Ferreira; Galland, Fabiana; Lirio, Franciane; Broetto, Núbia; Nardin, Patrícia; Gonçalves, Carlos-Alberto

2016-02-01

Diabetes is a metabolic disease characterized by high fasting-glucose levels. Diabetic complications have been associated with hyperglycemia and high levels of reactive compounds, such as methylglyoxal (MG) and advanced glycation endproducts (AGEs) formation derived from glucose. Diabetic patients have a higher risk of developing neurodegenerative diseases, such as Alzheimer's disease or Parkinson's disease. Herein, we examined the effect of high glucose, MG and carboxyethyllysine (CEL), a MG-derived AGE of lysine, on oxidative, metabolic and astrocyte-specific parameters in acute hippocampal slices, and investigated some of the mechanisms that could mediate these effects. Glucose, MG and CEL did not alter reactive oxygen species (ROS) formation, glucose uptake or glutamine synthetase activity. However, glutamate uptake and S100B secretion were decreased after MG and CEL exposure. RAGE activation and glycation reactions, examined by aminoguanidine and L-lysine co-incubation, did not mediate these changes. Acute MG and CEL exposure, but not glucose, were able to induce similar effects on hippocampal slices, suggesting that conditions of high glucose concentrations are primarily toxic by elevating the rates of these glycation compounds, such as MG, and by generation of protein cross-links. Alterations in the secretion of S100B and the glutamatergic activity mediated by MG and AGEs can contribute to the brain dysfunction observed in diabetic patients.

Direct electron transfer of glucose oxidase and dual hydrogen peroxide and glucose detection based on water-dispersible carbon nanotubes derivative.

PubMed

Chen, Hsiao-Chien; Tu, Yi-Ming; Hou, Chung-Che; Lin, Yu-Chen; Chen, Ching-Hsiang; Yang, Kuang-Hsuan

2015-03-31

A water-dispersible multi-walled carbon nanotubes (MWCNTs) derivative, MWCNTs-1-one-dihydroxypyridine (MWCNTs-Py) was synthesis via Friedel-Crafts chemical acylation. Raman spectra demonstrated the conjugated level of MWCNTs-Py was retained after this chemical modification. MWCNTs-Py showed dual hydrogen peroxide (H2O2) and glucose detections without mutual interference by adjusting pH value. It was sensitive to H2O2 in acidic solution and displayed the high performances of sensitivity, linear range, response time and stability; meanwhile it did not respond to H2O2 in neutral solution. In addition, this positively charged MWCNTs-Py could adsorb glucose oxidase (GOD) by electrostatic attraction. MWCNTs-Py-GOD/GC electrode showed the direct electron transfer (DET) of GOD with a pair of well-defined redox peaks, attesting the bioactivity of GOD was retained due to the non-destroyed immobilization. The high surface coverage of active GOD (3.5×10(-9) mol cm(-2)) resulted in exhibiting a good electrocatalytic activity toward glucose. This glucose sensor showed high sensitivity (68.1 μA mM(-1) cm(-2)) in a linear range from 3 μM to 7 mM in neutral buffer solution. The proposed sensor could distinguish H2O2 and glucose, thus owning high selectivity and reliability. Copyright © 2015. Published by Elsevier B.V.

Effects of tolbutamide and N-benzoyl-D-phenylalanine (NBDP) on the regulation of [Ca2+]i oscillations in mouse pancreatic islets.

PubMed

Lenzen, S; Peckmann, T

2001-10-01

The sulfonylurea derivative, tolbutamide, and the phenylalanine derivative, N-benzoyl-D-phenylalanine (NBDP), both of which stimulate insulin secretion through interaction with the sulfonylurea receptor (SUR1), were studied for their ability to increase the [Ca(2+)](i) and to interact with the glucose-induced slow large amplitude [Ca(2+)](i) oscillations in isolated mouse pancreatic islets. Tolbutamide as well as NBDP induced [Ca(2+)](i) oscillations of extremely slow frequency. Both compounds also lowered the threshold for the glucose-induced slow large amplitude [Ca(2+)](i) oscillations and significantly reduced their frequency in intact islets as well as in single pancreatic beta cells. These [Ca(2+)](i) oscillations apparently require a glucokinase-mediated glycolytic flux. This conclusion is supported by the observations that KIC, a mitochondrial fuel, cannot replace glucose in this synergism and that mannoheptulose, an inhibitor of glucokinase and glucose-induced insulin secretion, abolishes these slow [Ca(2+)](i) oscillations. In conclusion, these compounds potentiate the effect of glucose. This additive effect is the likely result of a synergistic closing action upon the ATP-sensitive K(+) (K(ATP)) channel, mediated in the case of glucose through an action upon the channel protein itself of ATP generated in glucose catabolism and in the case of tolbutamide and NBDP upon the sulfonylurea receptor (SUR1) associated with this channel.

Comparable Dietary Patterns Describe Dietary Behavior across Ethnic Groups in the Netherlands, but Different Elements in the Diet Are Associated with Glycated Hemoglobin and Fasting Glucose Concentrations.

PubMed

Dekker, Louise H; van Dam, Rob M; Snijder, Marieke B; Peters, Ron J G; Dekker, Jacqueline M; de Vries, Jeanne H M; de Boer, Evelien J; Schulze, Matthias B; Stronks, Karien; Nicolaou, Mary

2015-08-01

Ethnic minority populations in Western societies suffer from a disproportionate burden of type 2 diabetes (T2D). Insight into the role of dietary patterns in T2D may assist public health nutrition efforts in addressing these health disparities. We explored the association between dietary patterns and biomarkers of T2D in 5 ethnic groups living in Amsterdam, Netherlands. A total of 3776 men and women aged 18-70 y of Dutch, South Asian Surinamese, African-Surinamese, Turkish, and Moroccan origin from the HELIUS (HEalthy LIfe in an Urban Setting) study were included. Diet was assessed by using a food-frequency questionnaire, and dietary patterns were derived separately per ethnic group. First, food group-based dietary patterns were derived by using principal components analysis and the association with glycated hemoglobin (HbA1c) and plasma fasting glucose was assessed by using multivariable linear regression. Second, biomarker-driven dietary patterns based on HbA1c and fasting glucose concentrations were derived by applying reduced rank regression. Two comparable food group-based dietary patterns were identified in each ethnic group: a "meat and snack" pattern and a "vegetable" pattern. The meat-and-snack pattern derived within the Dutch origin population was significantly associated with HbA1c (β = 0.09; 95% CI: 0.00, 0.19) and fasting glucose (β = 0.18; 95% CI: 0.09, 0.26) concentrations. A biomarker-derived pattern characterized by red and processed meat was observed among Dutch-origin participants; however, among ethnic minority groups, this pattern was characterized by other foods including ethnicity-specific foods (e.g., roti, couscous). Although similar food group dietary patterns were derived within 5 ethnic groups, the association of the meat-and-snack pattern with fasting glucose concentrations differed by ethnicity. Taken together with the finding of ethnic differences in biomarker-driven dietary patterns, our results imply that addressing T2D risk in multiethnic populations requires ethnicity-specific approaches. © 2015 American Society for Nutrition.

99mTc-EDDA/HYNIC-TOC in the diagnosis of differentiated thyroid carcinoma refractory to radioiodine treatment.

PubMed

Czepczyński, Rafał; Gryczyńska, Maria; Ruchała, Marek

2016-01-01

In majority of cases of differentiated thyroid carcinoma (DTC), the ablative radioiodine treatment shows high efficacy. In a small number of patients, mechanism of selective iodine uptake by the DTC cells is insufficient and alternative methods of diagnosis and treatment are needed. As demonstrated in vitro, DTC cells show expression of somatostatin recep-tors. Radiolabeled somatostatin analogs are widely used in the diagnosis of neuroendocrine tumors. The aim of the study was to evaluate the utility of peptide receptor scintigraphy with the use of 99mTc-EDDA/HYNIC-TOC in the diagnosis of DTC in patients with elevated thyroglobulin concentrations (Tg), negative WBS and no effect of the consecutive radioiodine therapies. Whole body scintigraphy as well as SPECT of neck and chest were performed 3 and 24 h after i.v. administration of 740 MBq 99mTc-EDDA/HYNIC-TOC. The obtained images were compared with other radionuclide and ra-diological imaging methods. Forty-three patients with DTC after surgery and ablative radioiodine treatment with negative WBS and elevated Tg were qualified. Patients' age: 18-83 years (mean 58.0). SRS showed foci of tracer accumulation in 29 cases (67.4%). Sensitivity was 69.0% specificity 78.6%. SRS correctly identified local recurrence in 8 pts., metastatic lymph nodes in 19 pts., lung metastases in 12 pts. and bone metastases in 5 pts. SRS showed high sensitivity in the detection of metastatic lymph nodes (100%) and bone metastases (83.3%) and lung metastases (63.2%). Positive SRS was found in pts. with higher Tg concentrations (130 ± 144 vs. 30 ± 54 ng/ml). Scintigraphy with the use of the studied technetium-99m-labeled somatostatin analog is useful in the evaluation of patients with advanced DTC. It shows relatively good sensitivity and specificity but not high enough to be recommended as a routine imaging method. The role of somatostatin receptor scintigraphy in DTC is complementary to other imaging modalities.

An imidazopyridine anxiolytic alters glucose tolerance in patients: a pilot investigation.

PubMed

Bottaï, T; Cartault, F; Pouget, R; Blayac, J P; Petit, P

1995-02-01

We have recently shown that compounds with high affinity for peripheral-type benzodiazepine receptors inhibited glucose-induced insulin secretion in vitro. We therefore performed an oral glucose tolerance test in anxious inpatients treated with the imidazopyridine derivative alpidem, which has been shown to display high affinity for these binding sites. The test was performed before and after 1 week of daily administration of the drug. As compared with pretreatment values, a significant alteration of the insulin response to glucose was observed. It is suggested that daily administration of alpidem, at therapeutically effective doses for the treatment of anxiety, may alter glucose tolerance.

Co-fermentation of glucose, xylose and/or cellobiose by yeast

DOEpatents

Jeffries, Thomas W.; Willis, Laura B.; Long, Tanya M.; Su, Yi-Kai

2013-09-10

Provided herein are methods of using yeast cells to produce ethanol by contacting a mixture comprising xylose with a Spathaspora yeast cell under conditions suitable to allow the yeast to ferment at least a portion of the xylose to ethanol. The methods allow for efficient ethanol production from hydrolysates derived from lignocellulosic material and sugar mixtures including at least xylose and glucose or xylose, glucose and cellobiose.

A PHGDH inhibitor reveals coordination of serine synthesis and 1-carbon unit fate

PubMed Central

Pacold, Michael E.; Brimacombe, Kyle R.; Chan, Sze Ham; Rohde, Jason M.; Lewis, Caroline A.; Swier, Lotteke J.Y.M.; Possemato, Richard; Chen, Walter W.; Sullivan, Lucas B.; Fiske, Brian P.; Cho, Sung Won; Freinkman, Elizaveta; Birsoy, Kıvanç; Abu-Remaileh, Monther; Shaul, Yoav D.; Liu, Chieh Min; Zhou, Minerva; Koh, Min Jung; Chung, Haeyoon; Davidson, Shawn M.; Luengo, Alba; Wang, Amy Q.; Xu, Xin; Yasgar, Adam; Liu, Li; Rai, Ganesha; Westover, Kenneth D.; Vander Heiden, Matthew G.; Shen, Min; Gray, Nathanael S.; Boxer, Matthew B.; Sabatini, David M.

2016-01-01

Serine is a both a proteinogenic amino acid and the source of one-carbon units essential for de novo purine and deoxythymidine synthesis. In the canonical glucose-derived serine synthesis pathway, Homo sapiens phosphoglycerate dehydrogenase (PHGDH) catalyzes the first, rate-limiting step. Genetic loss of PHGDH is toxic towards PHGDH-overexpressing breast cancer cell lines even in the presence of exogenous serine. Here, we use a quantitative high-throughput screen to identify small molecule PHGDH inhibitors. These compounds reduce the production of glucose-derived serine in cells and suppress the growth of PHGDH-dependent cancer cells in culture and in orthotopic xenograft tumors. Surprisingly, PHGDH inhibition reduced the incorporation into nucleotides of one-carbon units from glucose-derived and exogenous serine. We conclude that glycolytic serine synthesis coordinates the use of one-carbon units from endogenous and exogenous serine in nucleotide synthesis, and suggest that one-carbon unit wasting may contribute to the efficacy of PHGDH inhibitors in vitro and in vivo. PMID:27110680

Biomass-derived oxygenate reforming on Pt(111): A demonstration of surface science using D-glucose and its model surrogate glycolaldehyde

NASA Astrophysics Data System (ADS)

McManus, Jesse R.; Yu, Weiting; Salciccioli, Michael; Vlachos, Dionisios G.; Chen, Jingguang G.; Vohs, John M.

2012-12-01

Molecules derived from cellulosic biomass, such as glucose, represent an important renewable feedstock for the production of hydrogen and hydrocarbon-based fuels and chemicals. Development of efficient catalysts for their reformation into useful products is needed; however, this requires a detailed understanding of their adsorption and reaction on catalytically active transition metal surfaces. In this paper we demonstrate that the standard surface science techniques routinely used to characterize the reaction of small molecules on metals are also amenable for use in studying the adsorption and reaction of complex biomass-derivatives on single crystal metal surfaces. In particular, Temperature Programmed Desorption (TPD) and High Resolution Electron Energy Loss Spectroscopy (HREELS) combined with Density Functional Theory (DFT) calculations were used to elucidate the adsorption configuration of D-glucose and glycolaldehye on Pt(111). Both molecules were found to adsorb in an η1 aldehyde configuration partially validating the use of simple, functionally-equivalent model compounds for surface studies of cellulosic oxygenates.

Treatment of type 1 diabetes with adipose tissue-derived stem cells expressing pancreatic duodenal homeobox 1.

PubMed

Lin, Guiting; Wang, Guifang; Liu, Gang; Yang, Li-Jun; Chang, Lung-Ji; Lue, Tom F; Lin, Ching-Shwun

2009-12-01

Due to the limited supply of donor pancreas, it is imperative that we identify alternative cell sources that can be used to treat diabetes mellitus (DM). Multipotent adipose tissue-derived stem cells (ADSC) can be abundantly and safely isolated for autologous transplantation and therefore are an ideal candidate. Here, we report the derivation of insulin-producing cells from human or rat ADSC by transduction with the pancreatic duodenal homeobox 1 (Pdx1) gene. RT-PCR analyses showed that native ADSC expressed insulin, glucagon, and NeuroD genes that were up-regulated following Pdx1 transduction. ELISA analyses showed that the transduced cells secreted increasing amount of insulin in response to increasing concentration of glucose. Transplantation of these cells under the renal capsule of streptozotocin-induced diabetic rats resulted in lowered blood glucose, higher glucose tolerance, smoother fur, and less cataract. Histological examination showed that the transplanted cells formed tissue-like structures and expressed insulin. Thus, ADSC-expressing Pdx1 appear to be suitable for treatment of DM.

Autophagy Inhibition Contributes to ROS-Producing NLRP3-Dependent Inflammasome Activation and Cytokine Secretion in High Glucose-Induced Macrophages.

PubMed

Dai, Jiezhi; Zhang, Xiaotian; Li, Li; Chen, Hua; Chai, Yimin

2017-01-01

Type 2 diabetes is a persistent inflammatory response that impairs the healing process. We hypothesized that stimulation with high glucose following a pro-inflammatory signal would lead to autophagy inhibition, reactive oxygen species (ROS) production and eventually to the activation of the Nod-like receptor protein (NLRP) -3. Macrophages were isolated from human diabetic wound. We measured the expression of NLRP3, caspase1 and interleukin-1 beta (IL-1β) by western blot and real-time PCR, and the surface markers on cells by flow cytometry. THP-1-derived macrophages exposed to high glucose were applied to study the link between autophagy, ROS and NLRP3 activation. LC3-II, P62, NLRP3 inflammation and IL-1β expression were measured by western blot and real-time PCR. ROS production was measured with a Cellular Reactive Oxygen Species Detection Assay Kit. Macrophages isolated from diabetic wounds exhibited a pro-inflammatory phenotype, including sustained NLRP3 inflammasome activity associated with IL-1β secretion. Our data showed that high glucose inhibited autophagy, induced ROS production, and activated NLRP3 inflammasome and cytokine secretion in THP-1-derived macrophages. To study high glucose-induced NLRP3 inflammasome signalling, we performed studies using an autophagy inducer, a ROS inhibitor and a NLRP3 inhibitor and found that all reduced the NLRP3 inflammasome activation and cytokine secretion. Sustained NLRP3 inflammasome activity in wound-derived macrophages contributes to the hyper-inflammation in human diabetic wounds. Autophagy inhibition and ROS generation play an essential role in high glucose-induced NLRP3 inflammasome activation and cytokine secretion in macrophages. © 2017 The Author(s). Published by S. Karger AG, Basel.

Long non-coding RNA nuclear paraspeckle assembly transcript 1 inhibits the apoptosis of retina Müller cells after diabetic retinopathy through regulating miR-497/brain-derived neurotrophic factor axis.

PubMed

Li, Xiu-Juan

2018-05-01

The role of long non-coding RNA in diabetic retinopathy, a serious complication of diabetes mellitus, has attracted increasing attention in recent years. The purpose of this study was to explore whether long non-coding RNA nuclear paraspeckle assembly transcript 1 was involved in the context of diabetic retinopathy and its underlying mechanisms. Our results revealed that nuclear paraspeckle assembly transcript 1 was significantly downregulated in the retina of diabetes mellitus rats. Meanwhile, miR-497 was significantly increased in diabetes mellitus rats' retina and high glucose-treated Müller cells, but brain-derived neurotrophic factor was increased. We also found that high glucose-induced apoptosis of Müller cells was accompanied by the significant downregulation of nuclear paraspeckle assembly transcript 1 in vitro. Further study demonstrated that high glucose-promoted Müller cells apoptosis through downregulating nuclear paraspeckle assembly transcript 1 and downregulated nuclear paraspeckle assembly transcript 1 mediated this effect via negative regulating miR-497. Moreover, brain-derived neurotrophic factor was negatively regulated by miR-497 and associated with the apoptosis of Müller cells under high glucose. Our results suggested that under diabetic conditions, downregulated nuclear paraspeckle assembly transcript 1 decreased the expression of brain-derived neurotrophic factor through elevating miR-497, thereby promoting Müller cells apoptosis and aggravating diabetic retinopathy.

Maintenance of biological activity of pertussis toxin radioiodinated while bound to fetuin-agarose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Armstrong, G.D.; Peppler, M.S.

1987-05-01

We developed a method to produce radioiodinated pertussis toxin (PT) which was active in the goose erythrocyte agglutination and CHO cell assay systems. The procedure used fetuin coupled to agarose to prevent inactivation of the toxin during the iodination reaction. Analysis of the labeled PT by affinity chromatography on fetuin-agarose and wheat germ agglutinin-agarose and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that there were minimal amounts of labeled fetuin or other contaminants in the labeled PT preparations. All five of the subunits of the toxin appeared to be labeled by the procedure. The labeling method will facilitate further investigationsmore » into the nature of the interaction and activity of PT in host tissues.« less

(99m)Tc HYNIC-TOC imaging and 177Lu DOTA-octreotate treatment in non-iodine-concentrating dedifferentiated thyroid carcinoma metastases: an unusual alternative diagnosis.

PubMed

Basu, Sandip; Joshi, Amit

2014-07-01

The value of Tc HYNIC-TOC scintigraphy clarifying skeletal and hepatic-predominant metastatic disease in a 55-year-old woman (diagnosed earlier to have papillary carcinoma thyroid and had undergone total thyroidectomy and radioiodine ablation) is illustrated. The whole-body radioiodine scan and battery of serum tumor markers were normal. Multiple metastatic foci in the liver and skeleton were Tc HYNIC-TOC avid. Serum chromogranin A level was substantially elevated (1771.60 ng/mL). This represents an unusual alternative diagnosis signified by a highly positive scan in the setting of apparent non-iodine-concentrating metastatic disease in a patient of differentiated thyroid carcinoma.

Thyroid and parathyroid imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sandler, M.P.; Patton, J.A.; Partain, C.L.

1986-01-01

This book describes the numerous modalities currently used in the diagnosis and treatment of both thyroid and parathyroid disorders. Each modality is fully explained and then evaluated in terms of benefits and limitations in the clinical context. Contents: Production and Quality Control of Radiopharmaceutics Used for Diagnosis and Therapy in Thyroid and Parathyroid Disorders. Basic Physics. Nuclear Instrumentation. Radioimmunoassay: Thyroid Function Tests. Quality Control. Embryology, Anatomy, Physiology, and Thyroid Function Studies. Scintigraphic Thyroid Imaging. Neonatal and Pediatric Thyroid Imaging. Radioiodine Thyroid Uptake Measurement. Radioiodine Treatment of Thyroid Disorders. Radiation Dosimetry of Diagnostic Procedures. Radiation Safety Procedures for High-Level I-131 Therapies.more » X-Ray Fluorescent Scanning. Thyroid Sonography. Computed Tomography in Thyroid Disease. Magnetic Resonance Imaging in Thyroid Disease. Parathyroid Imaging.« less

Cyclotron production of I-123: An evaluation of the nuclear reactions which produce this isotope

NASA Technical Reports Server (NTRS)

Sodd, V. J.; Scholz, K. L.; Blue, J. W.; Wellman, H. N.

1970-01-01

The use of the various nuclear reactions is described by which I-123,a low radiation dose radiopharmaceutical, can be cyclotron-produced. Methods of directly producing I-123 and those which indirectly produce the radionuclide through the beta (+) decay of its nautral precursor, Xe-123. It is impossible to separate from the radioiodine contaminants, notably I-124, which occur in the direct method. Thus, it is preferable to produce pure I-123 from Xe-123 which is easily separated from the radioiodines. Among the characteristics of I-123 is the capability of reducing the patient dose in a thyroid uptake measurement to a very small percentage of that delivered by the more commonly used I-131.

Glucocorticoid Signaling Enhances Expression of Glucose-Sensing Molecules in Immature Pancreatic Beta-Like Cells Derived from Murine Embryonic Stem Cells In Vitro.

PubMed

Ghazalli, Nadiah; Wu, Xiaoxing; Walker, Stephanie; Trieu, Nancy; Hsin, Li-Yu; Choe, Justin; Chen, Chialin; Hsu, Jasper; LeBon, Jeanne; Kozlowski, Mark T; Rawson, Jeffrey; Tirrell, David A; Yip, M L Richard; Ku, Hsun Teresa

2018-06-06

Pluripotent stem cells may serve as an alternative source of beta-like cells for replacement therapy of type 1 diabetes; however, the beta-like cells generated in many differentiation protocols are immature. The maturation of endogenous beta cells involves an increase in insulin expression starting in late gestation and a gradual acquisition of the abilities to sense glucose and secrete insulin by week 2 after birth in mice; however, what molecules regulate these maturation processes are incompletely known. In this study, we aim to identify small molecules that affect immature beta cells. A cell-based assay, using pancreatic beta-like cells derived from murine embryonic stem (ES) cells harboring a transgene containing an insulin 1-promoter driven enhanced green fluorescent protein reporter, was used to screen a compound library (NIH Clinical Collection-003). Cortisone, a glucocorticoid, was among five positive hit compounds. Quantitative reverse transcription-polymerase chain reaction analysis revealed that glucocorticoids enhance the gene expression of not only insulin 1 but also glucose transporter-2 (Glut2; Slc2a2) and glucokinase (Gck), two molecules important for glucose sensing. Mifepristone, a pharmacological inhibitor of glucocorticoid receptor (GR) signaling, reduced the effects of glucocorticoids on Glut2 and Gck expression. The effects of glucocorticoids on ES-derived cells were further validated in immature primary islets. Isolated islets from 1-week-old mice had an increased Glut2 and Gck expression in response to a 4-day treatment of exogenous hydrocortisone in vitro. Gene deletion of GR in beta cells using rat insulin 2 promoter-driven Cre crossed with GR flox/flox mice resulted in a reduced gene expression of Glut2, but not Gck, and an abrogation of insulin secretion when islets were incubated in 0.5 mM d-glucose and stimulated by 17 mM d-glucose in vitro. These results demonstrate that glucocorticoids positively regulate glucose sensors in immature murine beta-like cells.

Atypical ethanol production by carbon catabolite derepressed lactobacilli.

PubMed

Kim, Jae-Han; Block, David E; Shoemaker, Sharon P; Mills, David A

2010-11-01

Cost effective use of lignocellulosic biomass for bio-based chemical production requires the discovery of novel strains and processes. Lactobacillus pentosus JH5XP5 is a carbon catabolite repression negative mutant which utilizes glucose and pentoses derived from lignocellulosic biomass in the media simultaneously. With a broad range of carbon substrates, L. pentosus JH5XP5 produced a significant amount of ethanol without acetate formation. The yields of ethanol were 2.0- to 2.5-fold higher than those of lactate when glucose, galactose or maltose was used either as a single carbon source or simultaneously with glucose. L. pentosus JH5XP5 was successfully used in an integrated process of simultaneous saccharification and mixed sugar fermentation of rice straw hydrolysate. During the fermentation, the enzyme activities for the saccharification of cellulose were not diminished. Moreover glucose, xylose, and arabinose sugars derived from rice straw hyrolysate were consumed concurrently as if a single carbon source existed and no sugars or cellulosic fiber remained after the fermentation.

[Amino sugars mineralization and its responses to exogenous substances in black soil of Northeast China].

PubMed

Zhang, Wei; He, Hong-bo; Xie, Hong-tu; Bai, Zhen; Zhang, Xu-dong

2010-10-01

By the method of intermittent leaching aerobic incubation, this paper studied the mineralization of three kinds of microbes-derived amino sugar (glucosamine, muramic acid, and galactosamine) in black soil of Northeast China, and the responses to glucose addition and glucose plus nitrogen amendment. The mineralization of the amino sugars was compound-specific. During incubation period, the content of muramic acid decreased by 25.4%, while that of glucosamine decreased by 7.1%, suggesting that bacteria-derived muramic acid was more inclined to be mineralized, compared with fungi-originated glucosamine. However, the mineralized amount of glucosamine (68.4 mg x kg(-1)) was greater than that of muramic acid (15.4 mg x kg(-1)). Both glucose addition and glucose plus nitrogen amendment improved the contents of glucosamine and muramic acid significantly, but the effect varied. The mineralization of galactosamine was much slower, and less affected by exogenous substances addition, indicating that galactosamine was more stable in test soil.

Oral administration of Dictyostelium differentiation-inducing factor 1 lowers blood glucose levels in streptozotocin-induced diabetic rats.

PubMed

Kawaharada, Ritsuko; Nakamura, Akio; Takahashi, Katsunori; Kikuchi, Haruhisa; Oshima, Yoshiteru; Kubohara, Yuzuru

2016-06-15

Differentiation-inducing factor 1 (DIF-1), originally discovered in the cellular slime mold Dictyostelium discoideum, and its derivatives possess pharmacological activities, such as the promotion of glucose uptake in non-transformed mammalian cells in vitro. Accordingly, DIFs are considered promising lead candidates for novel anti-diabetic drugs. The aim of this study was to assess the anti-diabetic and toxic effects of DIF-1 in mouse 3T3-L1 fibroblast cells in vitro and in diabetic rats in vivo. Main methods We investigated the in vitro effects of DIF-1 and DIF-1(3M), a derivative of DIF-1, on glucose metabolism in 3T3-L1 cells by using capillary electrophoresis time-of-flight mass spectrometry (CE-TOF-MS). We also examined the effects of DIF-1 on blood glucose levels in streptozotocin (STZ)-induced rats. CE-TOF-MS revealed that 20μM DIF-1 and 20μM DIF-1(3M) promoted glucose uptake and metabolism in 3T3-L1 cells. Oral administration of DIF-1 (30mg/kg) significantly lowered basal blood glucose levels in STZ-treated rats and promoted a decrease in blood glucose levels after oral glucose loading (2.5g/kg) in the rats. In addition, daily oral administration of DIF-1 (30mg/kg/day) for 1wk significantly lowered the blood glucose levels in STZ-treated rats but did not affect their body weight and caused only minor alterations in the levels of other blood analytes. These results indicate that DIF-1 may be a good lead compound for the development of anti-diabetic drugs. Copyright © 2016 Elsevier Inc. All rights reserved.

Valsartan Improves β-Cell Function and Insulin Sensitivity in Subjects With Impaired Glucose Metabolism

PubMed Central

van der Zijl, Nynke J.; Moors, Chantalle C.M.; Goossens, Gijs H.; Hermans, Marc M.H.; Blaak, Ellen E.; Diamant, Michaela

2011-01-01

OBJECTIVE Recently, the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research Trial demonstrated that treatment with the angiotensin receptor blocker (ARB) valsartan for 5 years resulted in a relative reduction of 14% in the incidence of type 2 diabetes in subjects with impaired glucose metabolism (IGM). We investigated whether improvements in β-cell function and/or insulin sensitivity underlie these preventive effects of the ARB valsartan in the onset of type 2 diabetes. RESEARCH DESIGN AND METHODS In this randomized controlled, double-blind, two-center study, the effects of 26 weeks of valsartan (320 mg daily; n = 40) or placebo (n = 39) on β-cell function and insulin sensitivity were assessed in subjects with impaired fasting glucose and/or impaired glucose tolerance, using a combined hyperinsulinemic-euglycemic and hyperglycemic clamp with subsequent arginine stimulation and a 2-h 75-g oral glucose tolerance test (OGTT). Treatment effects were analyzed using ANCOVA, adjusting for center, glucometabolic status, and sex. RESULTS Valsartan increased first-phase (P = 0.028) and second-phase (P = 0.002) glucose-stimulated insulin secretion compared with placebo, whereas the enhanced arginine-stimulated insulin secretion was comparable between groups (P = 0.25). In addition, valsartan increased the OGTT-derived insulinogenic index (representing first-phase insulin secretion after an oral glucose load; P = 0.027). Clamp-derived insulin sensitivity was significantly increased with valsartan compared with placebo (P = 0.049). Valsartan treatment significantly decreased systolic and diastolic blood pressure compared with placebo (P < 0.001). BMI remained unchanged in both treatment groups (P = 0.89). CONCLUSIONS Twenty-six weeks of valsartan treatment increased glucose-stimulated insulin release and insulin sensitivity in normotensive subjects with IGM. These findings may partly explain the beneficial effects of valsartan in the reduced incidence of type 2 diabetes. PMID:21330640

Uptake of a fluorescent L-glucose derivative 2-NBDLG into three-dimensionally accumulating insulinoma cells in a phloretin-sensitive manner.

PubMed

Sasaki, Ayako; Nagatomo, Katsuhiro; Ono, Koki; Yamamoto, Toshihiro; Otsuka, Yuji; Teshima, Tadashi; Yamada, Katsuya

2016-01-01

Of two stereoisomers of glucose, only D- and not L-glucose is abundantly found in nature, being utilized as an essential fuel by most organisms. The uptake of D-glucose into mammalian cells occurs through glucose transporters such as GLUTs, and this process has been effectively monitored by a fluorescent D-glucose derivative 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose (2-NBDG) at the single cell level. However, since fluorescence is an arbitrary measure, we have developed a fluorescent analog of L-glucose 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-L-glucose (2-NBDLG), as a negative control substrate for more accurately identifying the stereoselectivity of the uptake. Interestingly, a small portion of mouse insulinoma cells MIN6 abundantly took up 2-NBDLG at a late culture stage (≳ 10 days in vitro, DIV) when multi-cellular spheroids exhibiting heterogeneous nuclei were formed, whereas no such uptake was detected at an early culture stage (≲ 6 DIV). The 2-NBDLG uptake was persistently observed in the presence of a GLUT inhibitor cytochalasin B. Neither D- nor L-glucose in 50 mM abolished the uptake. No significant inhibition was detected by inactivating sodium/glucose cotransporters (SGLTs) with Na(+)-free condition. To our surprise, the 2-NBDLG uptake was totally inhibited by phloretin, a broad spectrum inhibitor against transporters/channels including GLUTs and aquaporins. From these, a question might be raised if non-GLUT/non-SGLT pathways participate in the 2-NBDLG uptake into spheroid-forming MIN6 insulinoma. It might also be worthwhile investigating whether 2-NBDLG can be used as a functional probe for detecting cancer, since the nuclear heterogeneity is among critical features of malignancy.

Enhancement of D-lactic acid production from a mixed glucose and xylose substrate by the Escherichia coli strain JH15 devoid of the glucose effect.

PubMed

Lu, Hongying; Zhao, Xiao; Wang, Yongze; Ding, Xiaoren; Wang, Jinhua; Garza, Erin; Manow, Ryan; Iverson, Andrew; Zhou, Shengde

2016-02-19

A thermal tolerant stereo-complex poly-lactic acid (SC-PLA) can be made by mixing Poly-D-lactic acid (PDLA) and poly-L-lactic acid (PLLA) at a defined ratio. This environmentally friendly biodegradable polymer could replace traditional recalcitrant petroleum-based plastics. To achieve this goal, however, it is imperative to produce optically pure lactic acid isomers using a cost-effective substrate such as cellulosic biomass. The roadblock of this process is that: 1) xylose derived from cellulosic biomass is un-fermentable by most lactic acid bacteria; 2) the glucose effect results in delayed and incomplete xylose fermentation. An alternative strain devoid of the glucose effect is needed to co-utilize both glucose and xylose for improved D-lactic acid production using a cellulosic biomass substrate. A previously engineered L-lactic acid Escherichia coli strain, WL204 (ΔfrdBC ΔldhA ΔackA ΔpflB ΔpdhR ::pflBp6-acEF-lpd ΔmgsA ΔadhE, ΔldhA::ldhL), was reengineered for production of D-lactic acid, by replacing the recombinant L-lactate dehydrogenase gene (ldhL) with a D-lactate dehydrogenase gene (ldhA). The glucose effect (catabolite repression) of the resulting strain, JH13, was eliminated by deletion of the ptsG gene which encodes for IIBC(glc) (a PTS enzyme for glucose transport). The derived strain, JH14, was metabolically evolved through serial transfers in screw-cap tubes containing glucose. The evolved strain, JH15, regained improved anaerobic cell growth using glucose. In fermentations using a mixture of glucose (50 g L(-1)) and xylose (50 g L(-1)), JH15 co-utilized both glucose and xylose, achieving an average sugar consumption rate of 1.04 g L(-1)h(-1), a D-lactic acid titer of 83 g L(-1), and a productivity of 0.86 g L(-1) h(-1). This result represents a 46 % improved sugar consumption rate, a 26 % increased D-lactic acid titer, and a 48 % enhanced productivity, compared to that achieved by JH13. These results demonstrated that JH15 has the potential for fermentative production of D-lactic acid using cellulosic biomass derived substrates, which contain a mixture of C6 and C5 sugars.

Nitrogenous compounds stimulate glucose-derived acid production by oral Streptococcus and Actinomyces.

PubMed

Norimatsu, Yuka; Kawashima, Junko; Takano-Yamamoto, Teruko; Takahashi, Nobuhiro

2015-09-01

Both Streptococcus and Actinomyces can produce acids from dietary sugars and are frequently found in caries lesions. In the oral cavity, nitrogenous compounds, such as peptides and amino acids, are provided continuously by saliva and crevicular gingival fluid. Given that these bacteria can also utilize nitrogen compounds for their growth, it was hypothesized that nitrogenous compounds may influence their acid production; however, no previous studies have examined this topic. Therefore, the present study aimed to assess the effects of nitrogenous compounds (tryptone and glutamate) on glucose-derived acid production by Streptococcus and Actinomyces. Acid production was evaluated using a pH-stat method under anaerobic conditions, whereas the amounts of metabolic end-products were quantified using high performance liquid chromatography. Tryptone enhanced glucose-derived acid production by up to 2.68-fold, whereas glutamate enhanced Streptococcus species only. However, neither tryptone nor glutamate altered the end-product profiles, indicating that the nitrogenous compounds stimulate the whole metabolic pathways involving in acid production from glucose, but are not actively metabolized, nor do they alter metabolic pathways. These results suggest that nitrogenous compounds in the oral cavity promote acid production by Streptococcus and Actinomyces in vivo. © 2015 The Societies and Wiley Publishing Asia Pty Ltd.

Tricarboxylic acid cycle inhibition by Li+ in the human neuroblastoma SH-SY5Y cell line: a 13C NMR isotopomer analysis.

PubMed

Fonseca, Carla P; Jones, John G; Carvalho, Rui A; Jeffrey, F Mark H; Montezinho, Liliana P; Geraldes, Carlos F G C; Castro, M M C A

2005-11-01

Li+ effects on glucose metabolism and on the competitive metabolism of glucose and lactate were investigated in the human neuroblastoma SH-SY5Y cell line using 13C NMR spectroscopy. The metabolic model proposed for glucose and lactate metabolism in these cells, based on tcaCALC best fitting solutions, for both control and Li+ conditions, was consistent with: (i) a single pyruvate pool; (ii) anaplerotic flux from endogenous unlabelled substrates; (iii) no cycling between pyruvate and oxaloacetate. Li+ was shown to induce a 38 and 53% decrease, for 1 and 15 mM Li+, respectively, in the rate of glucose conversion into pyruvate, when [U-13C]glucose was present, while no effects on lactate production were observed. Pyruvate oxidation by the tricarboxylic acid cycle and citrate synthase flux were shown to be significantly reduced by 64 and 84% in the presence of 1 and 15 mM Li+, respectively, suggesting a direct inhibitory effect of Li+ on tricarboxylic acid cycle flux. This work also showed that when both glucose and lactate are present as energetic substrates, SH-SY5Y cells preferentially consumed exogenous lactate over glucose, as 62% of the acetyl-CoA was derived from [3-13C]lactate while only 26% was derived from [U-13C]glucose. Li+ did not significantly affect the relative utilisation of these two substrates by the cells or the residual contribution of unlabelled endogenous sources for the acetyl-CoA pool.

Fluorescent 6-amino-6-deoxyglycoconjugates for glucose transporter mediated bioimaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Xiangyin; Liu, Shengnan; Liu, Xinyu

Two novel fluorescent bioprobes, namely, 6N-Gly-Cy3 and 6N-Gly-Cy5, were designed and synthesized for real-time glucose transport imaging as well as potentially useful tracer for galactokinase metabolism. The structure of the bioprobes was fully characterized by {sup 1}H NMR, {sup 13}C NMR, IR, and HRMS. The fluorescence properties, glucose transporter (GLUT) specificity, and the quenching and safety profiles were studied. The cellular uptake of both bioprobes was competitively diminished by D-glucose, 2-deoxy-D-glucose and GLUT specific inhibitor in a dose-dependent manner in human colon cancer cells (HT29). Comparison study results revealed that the 6N-derived bioprobes are more useful for real-time imaging ofmore » cell-based glucose uptake than the structurally similar fluorescent tracer 6-NBDG which was not applicable under physiological conditions. The up to 96 h long-lasting quenching property of 6N-Gly-Cy5 in HT29 suggested the potential applcability of the probe for cell labeling in xenograft transplantation as well as in vivo animal imaging studies. - Highlights: • Cy-3 and Cy-5 derived fluorescent 6-amino-6-deoxyglycoconjugates were prepared for glucose transporter mediated bioimaging. • The cellular uptake of the probes was inhibited by natural GLUT substrates and inhibitor. • The probes are useful for real-time imaging of cell-based glucose uptake under physiological conditions. • The probes showed up to 96 h long-lasting quenching profile in labeled cancer cells.« less

Mechanisms for antidiabetic effect of gingerol in cultured cells and obese diabetic model mice.

PubMed

Son, Myoung Jin; Miura, Yutaka; Yagasaki, Kazumi

2015-08-01

There have been studies on health beneficial effects of ginger and its components. However, there still remain certain aspects that are not well defined in their anti-hyperglycemic effects. Our aims were to find evidence of possible mechanisms for antidiabetic action of [6]-gingerol, a pungent component of ginger, employing a rat skeletal muscle-derived cell line, a rat-derived pancreatic β-cell line, and type 2 diabetic model animals. The antidiabetic effect of [6]-gingerol was investigated through studies on glucose uptake in L6 myocytes and on pancreatic β-cell protective ability from reactive oxygen species (ROS) in RIN-5F cells. Its in vivo effect was also examined using obese diabetic db/db mice. [6]-Gingerol increased glucose uptake under insulin absent condition and induced 5' adenosine monophosphate-activated protein kinase phosphorylation in L6 myotubes. Promotion by [6]-gingerol of glucose transporter 4 (GLUT4) translocation to plasma membrane was visually demonstrated by immunocytochemistry in L6 myoblasts transfected with glut4 cDNA-coding vector. [6]-Gingerol suppressed advanced glycation end product-induced rise of ROS levels in RIN-5F pancreatic β-cells. [6]-Gingerol feeding suppressed the increases in fasting blood glucose levels and improved glucose intolerance in db/db mice. [6]-Gingerol regulated hepatic gene expression of enzymes related to glucose metabolism toward decreases in gluconeogenesis and glycogenolysis as well as an increase in glycogenesis, thereby contributing to reductions in hepatic glucose production and hence blood glucose concentrations. These in vitro and in vivo results strongly suggest that [6]-gingerol has antidiabetic potential through multiple mechanisms.

Glucose inhibits cardiac muscle maturation through nucleotide biosynthesis.

PubMed

Nakano, Haruko; Minami, Itsunari; Braas, Daniel; Pappoe, Herman; Wu, Xiuju; Sagadevan, Addelynn; Vergnes, Laurent; Fu, Kai; Morselli, Marco; Dunham, Christopher; Ding, Xueqin; Stieg, Adam Z; Gimzewski, James K; Pellegrini, Matteo; Clark, Peter M; Reue, Karen; Lusis, Aldons J; Ribalet, Bernard; Kurdistani, Siavash K; Christofk, Heather; Nakatsuji, Norio; Nakano, Atsushi

2017-12-12

The heart switches its energy substrate from glucose to fatty acids at birth, and maternal hyperglycemia is associated with congenital heart disease. However, little is known about how blood glucose impacts heart formation. Using a chemically defined human pluripotent stem-cell-derived cardiomyocyte differentiation system, we found that high glucose inhibits the maturation of cardiomyocytes at genetic, structural, metabolic, electrophysiological, and biomechanical levels by promoting nucleotide biosynthesis through the pentose phosphate pathway. Blood glucose level in embryos is stable in utero during normal pregnancy, but glucose uptake by fetal cardiac tissue is drastically reduced in late gestational stages. In a murine model of diabetic pregnancy, fetal hearts showed cardiomyopathy with increased mitotic activity and decreased maturity. These data suggest that high glucose suppresses cardiac maturation, providing a possible mechanistic basis for congenital heart disease in diabetic pregnancy.

Glucose inhibits cardiac muscle maturation through nucleotide biosynthesis

PubMed Central

Nakano, Haruko; Minami, Itsunari; Braas, Daniel; Pappoe, Herman; Wu, Xiuju; Sagadevan, Addelynn; Vergnes, Laurent; Fu, Kai; Morselli, Marco; Dunham, Christopher; Ding, Xueqin; Stieg, Adam Z; Gimzewski, James K; Pellegrini, Matteo; Clark, Peter M; Reue, Karen; Lusis, Aldons J; Ribalet, Bernard; Kurdistani, Siavash K; Christofk, Heather; Nakatsuji, Norio

2017-01-01

The heart switches its energy substrate from glucose to fatty acids at birth, and maternal hyperglycemia is associated with congenital heart disease. However, little is known about how blood glucose impacts heart formation. Using a chemically defined human pluripotent stem-cell-derived cardiomyocyte differentiation system, we found that high glucose inhibits the maturation of cardiomyocytes at genetic, structural, metabolic, electrophysiological, and biomechanical levels by promoting nucleotide biosynthesis through the pentose phosphate pathway. Blood glucose level in embryos is stable in utero during normal pregnancy, but glucose uptake by fetal cardiac tissue is drastically reduced in late gestational stages. In a murine model of diabetic pregnancy, fetal hearts showed cardiomyopathy with increased mitotic activity and decreased maturity. These data suggest that high glucose suppresses cardiac maturation, providing a possible mechanistic basis for congenital heart disease in diabetic pregnancy. PMID:29231167

Cardiomyocyte exosomes regulate glycolytic flux in endothelium by direct transfer of GLUT transporters and glycolytic enzymes.

PubMed

Garcia, Nahuel A; Moncayo-Arlandi, Javier; Sepulveda, Pilar; Diez-Juan, Antonio

2016-03-01

Cardiomyocytes (CMs) and endothelial cells (ECs) have an intimate anatomical relationship, which is essential for maintaining the metabolic requirements of the heart. Little is known about the mechanisms that regulate nutrient flow from ECs to associated CMs, especially in situations of acute stress when local active processes are required to regulate endothelial transport. We examined whether CM-derived exosomes can modulate glucose transport and metabolism in ECs. In conditions of glucose deprivation, CMs increase the synthesis and secretion of exosomes. These exosomes are loaded with functional glucose transporters and glycolytic enzymes, which are internalized by ECs, leading to increased glucose uptake, glycolytic activity, and pyruvate production in recipient cells. These findings establish CM-derived exosomes as key components of the cardio-endothelial communication system which, through intercellular protein complementation, would allow a rapid response from ECs to increase glucose transport and a putative uptake of metabolic fuels from blood to CMs. This CM-EC protein complementation process might have implications for metabolic regulation in health and disease. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Dosimetry-based treatment for Graves' disease.

PubMed

Hyer, Steve L; Pratt, Brenda; Gray, Matthew; Chittenden, Sarah; Du, Yong; Harmer, Clive L; Flux, Glenn D

2018-06-01

The aim of this retrospective study was to assess the long-term outcome of a personalized dosimetry approach in Graves' disease aiming to render patients euthyroid from a planned thyroid absorbed dose of 60 Gy. A total of 284 patients with Graves' disease were followed prospectively following administration of radioiodine calculated to deliver an absorbed dose of 60 Gy. Patients with cardiac disease were excluded. Outcomes were analysed at yearly intervals for up to 10 years with a median follow-up of 37.5 months. A single radioiodine administration was sufficient to render a patient either euthyroid or hypothyroid in 175 (62%) patients, the remainder requiring further radioiodine. The median radioactivity required to deliver 60 Gy was 77 MBq. Less than 2% patients required 400-600 MBq, the standard activity administered in many centres. In the cohort receiving a single administration, 38, 32 and 26% were euthyroid on no specific thyroid medication at 3, 5 and 10 years, respectively. Larger thyroid volumes were associated with the need for further therapy. The presence of nodules on ultrasonography did not adversely affect treatment outcome. A personalized dosimetric approach delayed the long-term onset of hypothyroidism in 26% of patients. This was achieved using much lower administered activities than currently recommended. Future studies will aim to identify those patients who would benefit most from this approach.

A novel Alaska pollack-derived peptide, which increases glucose uptake in skeletal muscle cells, lowers the blood glucose level in diabetic mice.

PubMed

Ayabe, Tatsuhiro; Mizushige, Takafumi; Ota, Wakana; Kawabata, Fuminori; Hayamizu, Kohsuke; Han, Li; Tsuji, Tomoko; Kanamoto, Ryuhei; Ohinata, Kousaku

2015-08-01

We found that the tryptic digest of Alaska pollack protein exhibits a glucose-lowering effect in KK-Ay mice, a type II diabetic model. We then searched for glucose-lowering peptides in the digest. Ala-Asn-Gly-Glu-Val-Ala-Gln-Trp-Arg (ANGEVAQWR) was identified from a peak of the HPLC fraction selected based on the glucose-lowering activity in an insulin resistance test using ddY mice. ANGEVAQWR (3 mg kg(-1)) decreased the blood glucose level after intraperitoneal administration. Among its fragment peptides, the C-terminal tripeptide, Gln-Trp-Arg (QWR, 1 mg kg(-1)), lowered the blood glucose level, suggesting that the C-terminal is critical for glucose-lowering activity. QWR also enhanced glucose uptake into C2C12, a mouse skeletal muscle cell line. QWR did not induce the phosphorylation of serine/threonine protein kinase B (Akt) and adenosine monophosphate-activated protein kinase (AMPK). We also demonstrated that QWR lowered the blood glucose level in NSY and KK-Ay, type II diabetic models.

Association of hyperfunctioning thyroid adenoma with thyroid cancer presenting as "trapping only" nodule at 99mTcO4- scintigraphy.

PubMed

dell'Erba, L; Gerundini, P; Caputo, M; Bagnasco, M

2003-11-01

Rarely may a non-hyperfunctioning thyroid nodule present as "hot" at Technetium-99m pertechnetate (99mTcO4-) and "cold" at radioiodine scintigraphy at late acquisitions. We report the case of a hyperthyroid female patient whose 99mTcO4- scintigraphy showed two "hot" nodules, whereas Iodide-131 (131I-) revealed a lack of indicator uptake by the larger, and intense uptake by the smaller nodule. The patient underwent surgery: histology demonstrated that the larger nodule, mismatched at pertechnetate vs iodine scintigraphy, was a papillary carcinoma. Our suggestion is to perform thyroid scintigraphy with radioiodine in hyperthyroid patients with more than one nodule concentrating pertechnetate, especially when an ultrasonographic pattern possibly suspect for malignancy is present.

[Management of hypothyroidism and hyperthyroidism].

PubMed

Jiskra, Jan

2015-10-01

Functional thyropathies present significant health risks for patients. Advanced functional thyropathies are always treated while indications for therapy of subclinical thyropathies are individual and often controversial. It is widely agreed that these disorders should be diagnosed and individuals should be followed. The drug of choice in substitution therapy of hypothyroidism is levothyroxine, in the treatment of hyperthyroidism it is methimazole. Administration of propylthiouracil should be limited to the first trimester of pregnancy, because its serious hepatotoxicity has been described. Hyperthyroidism based on thyroid nodules and immunogenic hyperthyroidism not reaching long-term remission, need to be treated radically: by surgery or radioiodine treatment. When radiation protection requirements are met, radioiodine can also be administered on an outpatient basis. Exceptionally, small doses of methimazole can be administered over an extended period of time in individual cases.

Influence of elastin-derived peptides, glucose, LDL and oxLDL on nitric oxide synthase expression in human umbilical artery endothelial cells.

PubMed

Garczorz, Wojciech; Francuz, Tomasz; Gmiński, Jan; Likus, Wirginia; Siemianowicz, Krzysztof; Jurczak, Teresa; Strzałka-Mrozik, Barbara

2011-01-01

Endothelial dysfunction plays an important role in the development of atherosclerosis. Elastin-derived peptides (EDP), hyperglycemia, hypercholesterolemia and oxidized LDL have a proven proatherosclerotic potential. Nitric oxide generated by endothelial nitric oxide synthase (eNOS; EC 1.14.13.39) is an important vasorelaxant. Here we studied the influence of those proatherosclerotic factors on eNOS gene and protein expression in artery-derived endothelial cells. Human umbilical artery endothelial cells (HUAEC) were incubated with or without: glucose (270 mg/dl), LDL (200 mg/dl), oxidized LDL (oxLDL 25 mg/dl) or κ-elastin (0.5 and 2.5 µg/ml). Gene expression was assessed by real time RT-PCR, whilst the eNOS protein by ELISA. In cells incubated with 2.5 µg/ml of κ-elastin, a 31 % increase of eNOS mRNA expression was observed, but the protein level remained unchanged. OxLDL, LDL and glucose decreased the eNOS protein level by 74 %, 37 % and 29 %, respectively. OxLDL decreased eNOS mRNA by 42 %. LDL non-significantly decreased eNOS mRNA expression. An elevated glucose level did not affect the eNOS mRNA expression. Hyperglycemia and an elevated level of LDL, particularly oxLDL, decreased the level of eNOS protein in endothelial cells. As κ-elastin did not decrease the expression of eNOS gene in HUAEC, the proatherogenic properties of elastin-derived peptides are unlikely to be due to their influence on eNOS.

Improved penicillin amidase production using a genetically engineered mutant of escherichia coli ATCC 11105

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robas, N.; Zouheiry, H.; Branlant, G.

Penicillin G amidase (PGA) is a key enzyme for the industrial production of penicillin G derivatives used in therapeutics. Escherichia coli ATCC 11105 is the more commonly used strain for PGA production. To improve enzyme yield, the authors constructed various recombinant E. coli HB 101 and ATCC 11105 strains. For each strain, PGA production was determined for various concentrations of glucose and phenylacetic acid (PAA) in the medium. The E. coli strain, G271, was identified as the best performer (800 U NIPAB/L). This strain was obtained as follows: an E. coli ATCC 11105 mutant (E. coli G133) was first selectedmore » based on a low negative effect of glucose on PGA production. This mutant was then transformed with a pBR322 derivative containing the PGA gene. Various experiments were made to try to understand the reason for the high productivity of E. coli G271. The host strain, E. coli G133, was found to be mutated in one (or more) gene(s) whose product(s) act(s) in trans on the PGA gene expression. Its growth is not inhibited by high glucose concentration in the medium. Interestingly, whereas glucose still exerts some negative effect on the PGA production by E. coli G133, PGA production by its transformant (E. coli G271) is stimulated by glucose. The reason for this stimulation is discussed. Transformation of E. coli G133 with a pBR322 derivative containing the HindIII fragment of the PGA gene, showed that the performance of E. coli G271 depends both upon the host strain properties and the plasmid structure. Study of the production by the less efficient E. coli HB101 derivatives brought some light on the mechanism of regulation of the PGA gene.« less

Automated control of an adaptive bi-hormonal, dual-sensor artificial pancreas and evaluation during inpatient studies

PubMed Central

Jacobs, Peter G.; El Youssef, Joseph; Castle, Jessica; Bakhtiani, Parkash; Branigan, Deborah; Breen, Matthew; Bauer, David; Preiser, Nicholas; Leonard, Gerald; Stonex, Tara; Preiser, Nicholas; Ward, W. Kenneth

2014-01-01

Automated control of blood glucose in patients with type 1 diabetes has not yet been fully implemented. The aim of this study was to design and clinically evaluate a system that integrates a control algorithm with off-the-shelf subcutaneous sensors and pumps to automate the delivery of the hormones glucagon and insulin in response to continuous glucose sensor measurements. The automated component of the system runs an adaptive proportional derivative control algorithm which determines hormone delivery rates based on the sensed glucose measurements and the meal announcements by the patient. We provide details about the system design and the control algorithm, which incorporates both a fading memory proportional derivative controller (FMPD) and an adaptive system for estimating changing sensitivity to insulin based on a glucoregulatory model of insulin action. For an inpatient study carried out in eight subjects using Dexcom SEVEN PLUS sensors, pre-study HbA1c averaged 7.6, which translates to an estimated average glucose of 171 mg/dL. In contrast, during use of the automated system, after initial stabilization, glucose averaged 145 mg/dL and subjects were kept within the euglycemic range (between 70 and 180 mg/dL) for 73.1% of the time, indicating improved glycemic control. A further study on five additional subjects in which we used a newer and more reliable glucose sensor (Dexcom G4 PLATINUM) and made improvements to the insulin and glucagon pump communication system resulted in elimination of hypoglycemic events. For this G4 study, the system was able to maintain subjects’ glucose levels within the near-euglycemic range for 71.6% of the study duration and the mean venous glucose level was 151 mg/dL. PMID:24835122

Enhanced isoprenoid production from xylose by engineered Saccharomyces cerevisiae.

PubMed

Kwak, Suryang; Kim, Soo Rin; Xu, Haiqing; Zhang, Guo-Chang; Lane, Stephan; Kim, Heejin; Jin, Yong-Su

2017-11-01

Saccharomyces cerevisiae has limited capabilities for producing fuels and chemicals derived from acetyl-CoA, such as isoprenoids, due to a rigid flux partition toward ethanol during glucose metabolism. Despite numerous efforts, xylose fermentation by engineered yeast harboring heterologous xylose metabolic pathways was not as efficient as glucose fermentation for producing ethanol. Therefore, we hypothesized that xylose metabolism by engineered yeast might be a better fit for producing non-ethanol metabolites. We indeed found that engineered S. cerevisiae on xylose showed higher expression levels of the enzymes involved in ethanol assimilation and cytosolic acetyl-CoA synthesis than on glucose. When genetic perturbations necessary for overproducing squalene and amorphadiene were introduced into engineered S. cerevisiae capable of fermenting xylose, we observed higher titers and yields of isoprenoids under xylose than glucose conditions. Specifically, co-overexpression of a truncated HMG1 (tHMG1) and ERG10 led to substantially higher squalene accumulation under xylose than glucose conditions. In contrast to glucose utilization producing massive amounts of ethanol regardless of aeration, xylose utilization allowed much less amounts of ethanol accumulation, indicating ethanol is simultaneously re-assimilated with xylose consumption and utilized for the biosynthesis of cytosolic acetyl-CoA. In addition, xylose utilization by engineered yeast with overexpression of tHMG1, ERG10, and ADS coding for amorphadiene synthase, and the down-regulation of ERG9 resulted in enhanced amorphadiene production as compared to glucose utilization. These results suggest that the problem of the rigid flux partition toward ethanol production in yeast during the production of isoprenoids and other acetyl-CoA derived chemicals can be bypassed by using xylose instead of glucose as a carbon source. Biotechnol. Bioeng. 2017;114: 2581-2591. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Temporal fluxomics reveals oscillations in TCA cycle flux throughout the mammalian cell cycle.

PubMed

Ahn, Eunyong; Kumar, Praveen; Mukha, Dzmitry; Tzur, Amit; Shlomi, Tomer

2017-11-06

Cellular metabolic demands change throughout the cell cycle. Nevertheless, a characterization of how metabolic fluxes adapt to the changing demands throughout the cell cycle is lacking. Here, we developed a temporal-fluxomics approach to derive a comprehensive and quantitative view of alterations in metabolic fluxes throughout the mammalian cell cycle. This is achieved by combining pulse-chase LC-MS-based isotope tracing in synchronized cell populations with computational deconvolution and metabolic flux modeling. We find that TCA cycle fluxes are rewired as cells progress through the cell cycle with complementary oscillations of glucose versus glutamine-derived fluxes: Oxidation of glucose-derived flux peaks in late G1 phase, while oxidative and reductive glutamine metabolism dominates S phase. These complementary flux oscillations maintain a constant production rate of reducing equivalents and oxidative phosphorylation flux throughout the cell cycle. The shift from glucose to glutamine oxidation in S phase plays an important role in cell cycle progression and cell proliferation. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Development of a Protocol for Automated Glucose Measurement Transmission Used in Clinical Decision Support Systems Based on the Continua Design Guidelines.

PubMed

Meyer, Markus; Donsa, Klaus; Truskaller, Thomas; Frohner, Matthias; Pohn, Birgit; Felfernig, Alexander; Sinner, Frank; Pieber, Thomas

2018-01-01

A fast and accurate data transmission from glucose meter to clinical decision support systems (CDSSs) is crucial for the management of type 2 diabetes mellitus since almost all therapeutic interventions are derived from glucose measurements. Aim was to develop a prototype of an automated glucose measurement transmission protocol based on the Continua Design Guidelines and to embed the protocol into a CDSS used by healthcare professionals. A literature and market research was performed to analyze the state-of-the-art and thereupon develop, integrate and validate an automated glucose measurement transmission protocol in an iterative process. Findings from literature and market research guided towards the development of a standardized glucose measurement transmission protocol using a middleware. The interface description to communicate with the glucose meter was illustrated and embedded into a CDSS. A prototype of an interoperable transmission of glucose measurements was developed and implemented in a CDSS presenting a promising way to reduce medication errors and improve user satisfaction.

Development and study of 99mTc-1-Thio-D-glucose for visualization of malignant tumors

NASA Astrophysics Data System (ADS)

Zeltchan, R.; Medvedeva, A.; Sinilkin, I.; Bragina, O.; Chernov, V.; Stasyuk, E.; Rogov, A.; Il'ina, E.; Skuridin, V.

2017-09-01

The preclinical studies of 99mTc-1-Thio-D-glucose, a new tumor-seeking agent based on technetium-99m-labeled glucose derivative, were conducted, and the feasibility of using this radiopharmaceutical for tumor visualization was studied. The preclinical studies were carried out strictly in accordance with the local legislation and were regulated by the generally accepted research standards. 99mTc-1-Thio-D-glucose was found to have optimal pharmacokinetic and physico-chemical properties for diagnostic imaging and was proved to belong to the low-toxic substances. The potential utility of 99mTc-1-thio-D-glucose for tumor imaging was studied in vitro and in vivo models. The present study demonstrated that 99mTc-1-Thio-D-glucose is a prospective radiopharmaceutical for cancer visualization.

Porous HKUST-1 derived CuO/Cu2O shell wrapped Cu(OH)2 derived CuO/Cu2O core nanowire arrays for electrochemical nonenzymatic glucose sensors with ultrahigh sensitivity

NASA Astrophysics Data System (ADS)

Yu, Cuiping; Cui, Jiewu; Wang, Yan; Zheng, Hongmei; Zhang, Jianfang; Shu, Xia; Liu, Jiaqin; Zhang, Yong; Wu, Yucheng

2018-05-01

Self-supported CuO/Cu2O@CuO/Cu2O core-shell nanowire arrays (NWAs) are successfully fabricated by a simple and efficient method in this paper. Anodized Cu(OH)2 NWAs could in-situ convert to HKUST-1 at room temperature easily. Cu(OH)2 NWAs cores and HKUST-1 shells transform into CuO/Cu2O simultaneously after calcinations and form CuO/Cu2O@CuO/Cu2O core-shell NWAs. This smart configuration of the core-shell structure not only avoids the agglomeration of the traditional MOF-derived materials in particle-shape, but also facilitates the ion diffusion and increases the active sites. This novel structure is employed as substrate to construct nonenzymatic glucose sensors. The results indicate that glucose sensor based on CuO/Cu2O@CuO/Cu2O core-shell NWAs presents ultrahigh sensitivity (10,090 μA mM-1 cm-2), low detection limit (0.48 μM) and wide linear range (0.99-1,330 μM). In addition, it also shows excellent anti-interference ability toward uric acid, ascorbic acid and L-Cysteine co-existing with glucose, good reproducibility and superior ability of real sample analysis.

Detoxification of tabun at physiological pH mediated by substituted β-cyclodextrin and glucose derivatives containing oxime groups.

PubMed

Brandhuber, Florian; Zengerle, Michael; Porwol, Luzian; Tenberken, Oliver; Thiermann, Horst; Worek, Franz; Kubik, Stefan; Reiter, Georg

2012-12-16

The ability of 13 β-cyclodextrin and 2 glucose derivatives containing substituents with oxime groups as nucleophilic components to accelerate the degradation of tabun at physiological pH has been evaluated. To this end, a qualitative and a quantitative enzymatic assay as well as a highly sensitive enantioselective GC-MS assay were used. In addition, an assay was developed that provided information about the mode of action of the investigated compounds. The results show that attachment of pyridinium-derived substituents with an aldoxime group in 3- or 4-position to a β-cyclodextrin ring affords active compounds mediating tabun degradation. Activities differ depending on the structure, the number, and the position of the substituent on the ring. Highest activity was observed for a β-cyclodextrin containing a 4-formylpyridinium oxime residue in 6-position of one glucose subunit, which detoxifies tabun with a half-time of 10.2 min. Comparison of the activity of this compound with that of an analog in which the cyclodextrin ring was replaced by a glucose residue demonstrated that the cyclodextrin is not necessary for activity but certainly beneficial. Finally, the results provide evidence that the mode of action of the cyclodextrin involves covalent modification of its oxime group rendering the scavenger inactive after reaction with the first tabun molecule. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Pathways of fluid transport and reabsorption across the peritoneal membrane.

PubMed

Asghar, R B; Davies, S J

2008-05-01

The three-pore model of peritoneal fluid transport predicts that once the osmotic gradient has dissipated, fluid reabsorption will be due to a combination of small-pore reabsorption driven by the intravascular oncotic pressure, and an underlying disappearance of fluid from the cavity by lymphatic drainage. Our study measured fluid transport by these pathways in the presence and absence of an osmotic gradient. Paired hypertonic and standard glucose-dwell studies were performed using radio-iodinated serum albumin as an intraperitoneal volume marker and changes in intraperitoneal sodium mass to determine small-pore versus transcellular fluid transport. Disappearance of iodinated albumin was considered to indicate lymphatic drainage. Variability in transcellular ultrafiltration was largely explained by the rate of small-solute transport across the membrane. In the absence of an osmotic gradient, fluid reabsorption occurred via the small-pore pathway, the rate being proportional to the small-solute transport characteristics of the membrane. In most cases, fluid removal from the peritoneal cavity by this pathway was faster than by lymphatic drainage. Our study shows that the three-pore model describes the pathways of peritoneal fluid transport well. In the presence of high solute transport, poor transcellular ultrafiltration was due to loss of the osmotic gradient and an enhanced small-pore reabsorption rate after this gradient dissipated.

Unknown biological effects of L-glucose, ALA, and PUFA.

PubMed

Yamada, Katsuya; Sato, Daisuke; Nakamura, Takao; Amano, Hizuru; Morimoto, Yuji

2017-09-01

Key substrates including glucose, amino acids, and fatty acids play core roles in nutrient metabolism. In this review, we describe phenomena observed when key substrates are applied to cells. We focused on three promising substrates: L-glucose derivatives, 5-aminolevulinic acid, and polyunsaturated fatty acid. Since they are assumed to give a specific reaction when they are transported into cells or metabolized in cells, they are expected to be applied in a clinical setting. We provide the latest knowledge regarding their behaviors and effects on cells.

Central GLP-1 receptor signalling accelerates plasma clearance of triacylglycerol and glucose by activating brown adipose tissue in mice.

PubMed

Kooijman, Sander; Wang, Yanan; Parlevliet, Edwin T; Boon, Mariëtte R; Edelschaap, David; Snaterse, Gido; Pijl, Hanno; Romijn, Johannes A; Rensen, Patrick C N

2015-11-01

Glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) agonism, used in the treatment of type 2 diabetes, has recently been shown to increase thermogenesis via the brain. As brown adipose tissue (BAT) produces heat by burning triacylglycerol (TG) and takes up glucose for de novo lipogenesis, the aim of this study was to evaluate the potential of chronic central GLP-1R activation by exendin-4 to facilitate clearance of lipids and glucose from the circulation by activating BAT. Lean and diet-induced obese (DIO) C57Bl/6J mice were used to explore the effect of a 5 day intracerebroventricular infusion of the GLP-1 analogue exendin-4 or vehicle on lipid and glucose uptake by BAT in both insulin-sensitive and insulin-resistant conditions. Central administration of exendin-4 in lean mice increased sympathetic outflow towards BAT and white adipose tissue (WAT), resulting in increased thermogenesis as evidenced by increased uncoupling protein 1 (UCP-1) protein levels and decreased lipid content, while the uptake of TG-derived fatty acids was increased in both BAT and WAT. Interestingly, in DIO mice, the effects on WAT were blunted, while exendin-4 still increased sympathetic outflow towards BAT and increased the uptake of plasma TG-derived fatty acids and glucose by BAT. These effects were accompanied by increased fat oxidation, lower plasma TG and glucose concentrations, and reduced body weight. Collectively, our results suggest that BAT activation may be a major contributor to the glucose- and TG-lowering effects of GLP-1R agonism.

Acute activation of GLP-1-expressing neurons promotes glucose homeostasis and insulin sensitivity

USDA-ARS?s Scientific Manuscript database

Glucagon-like peptides are co-released from enteroendocrine L cells in the gut and preproglucagon (PPG) neurons in the Brainstem. PPG-derived GLP-1/2 are probably key neuroendocrine signals for the control of energy balance and glucose Homeostasis. The objective of this study was to determine whethe...

Regulation of ATP-binding cassette transporters and cholesterol efflux by glucose in primary human monocytes and murine bone marrow-derived macrophages

USDA-ARS?s Scientific Manuscript database

Individuals with type 2 diabetes mellitus are at increased risk of developing atherosclerosis. This may be partially attributable to suppression of macrophage ATP-binding cassette (ABC) transporter mediated cholesterol efflux by sustained elevated blood glucose concentrations. Two models were used...

Recombinant human thyrotropin stimulation prior to 131I therapy in toxic multinodular goitre with low radioactive iodine uptake.

PubMed

Azorín Belda, M J; Martínez Caballero, A; Figueroa Ardila, G C; Martínez Ramírez, M; Gómez Jaramillo, C A; Dolado Ardit, J I; Verdú Rico, J

Stimulation with recombinant human thyrotropin (rhTSH) increases thyroid radioiodine uptake, and is an aid to 131 I therapy in non-toxic multinodular goitre (MNG). However, there are not many studies using rhTSH prior to 131 I in toxic multinodular goitre to improve hyperthyroidism and compressive symptoms. A prospective study was conducted on patients with MNG and hyperthyroidism. Patients were recruited consecutively and divided into group I, stimulated with 0.3mg of rhTSH before radioiodine therapy, and a control group or group II, without stimulation. Thyroid function, radioiodine thyroid uptake, thyroid weight, and compressive symptoms were measured, and patients were followed-up for 9 months. Group I consisted of 16 patients (14 women), with a mean age 69.7 years, and group II with 16 patients (12 women), with a mean age 70.7 years. After stimulation with 0.3mg rhTSH in group I, 131 I uptake (RAIU) at 24h increased by 78.4%, and the estimated absorbed dose by 89.3%. In group II, the estimated absorbed dose was lower than group I after stimulation with rhTSH (29.8Gy vs. 56.4Gy; P=0.001). At 9 months of follow-up, hyperthyroidism was controlled in 87.5% of patients in group I, and 56.2% in group II (P=0.049). The mean reduction in thyroid weight was higher in group I than in group II (39.3% vs. 26.9%; P=0.017), with a tendency towards subjective improvement of compressive symptoms in group I, although non-significant. Only 2 patients described tachycardias after rhTSH administration, which were resolved with beta-blockers. Stimulation with 0.3mg of recombinant human thyrotropin prior to radioiodine therapy achieves a reduction in thyroid weight and functional improvement in patients with hyperthyroidism and multinodular goitre with low uptake, and with no need for hospital admission. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Radioiodine: the classic theranostic agent.

PubMed

Silberstein, Edward B

2012-05-01

Radioiodine has the distinction of being the first theranostic agent in our armamentarium. Millennia were required to discover that the agent in orally administered seaweed and its extracts, which had been shown to cure neck swelling due to thyromegaly, was iodine, first demonstrated to be a new element in 1813. Treatment of goiter with iodine began at once, but its prophylactic value to prevent a common form of goiter took another century. After Enrico Fermi produced the first radioiodine, (128)I, in 1934, active experimentation in the United States and France delineated the crucial role of iodine in thyroid metabolism and disease. (130)I and (131)I were first employed to treat thyrotoxicosis by 1941, and thyroid cancer in 1943. After World War II, (131)I became widely available at a reasonable price for diagnostic testing and therapy. The rectilinear scanner of Cassen and Curtis (Science 1949;110:94-95), and a dedicated gamma camera invented by Anger (Nature 1952;170:200-201), finally permitted the diagnostic imaging of thyroid disease, with (131)I again the radioisotope of choice, although there were short-lived attempts to employ (125)I and (132)I for this purpose. (123)I was first produced in 1949 but did not become widely available until about 1982, 10 years after a production technique eliminated high-energy (124)I contamination. I continues to be the radioiodine of choice for the diagnosis of benign thyroid disease, whereas (123)I and (131)I are employed in the staging and detection of functioning thyroid cancer. (124)I, a positron emitter, can produce excellent anatomically correlated images employing positron emission tomography/computed tomography equipment and has the potential to enhance heretofore imperfect dosimetric studies in determining the appropriate administered activity to ablate/treat thyroid cancer. Issues of acceptable measuring error in thyroid cancer dosimetry and the role in (131)I therapy of tumor heterogeneity, tumor hypoxia, and kinetics must be overcome, and long-term outcome studies following (131)I given based on this new dosimetry must be completed before the nuclear medicine community will be able to predictably cure our thyroid cancer patients with this technology. Copyright © 2012 Elsevier Inc. All rights reserved.

The Role of Radiopharmaceuticals in Amiodarone-Induced Thyroid Pathology.

PubMed

Irimie, Alexandru; Piciu, Doina

2017-11-10

The use of amiodarone for the treatment of ventricular and supraventricular dysrhythmias brings in organism an increased amount of iodine, interfering with thyroid function. If the treatment needs to be interrupted, iodine remains at abnormal levels for months or even years. The aim of the study was to review the literature regarding the optimal tests for early diagnostic and to analyze the role of nuclear medicine tests in the differential and correct assessment of the amiodarone-induced thyroid pathology. We made a review of available publications in PUBMED referring the amiodaroneinduced thyroid pathology, focusing on the differential diagnosis, made by nuclear medicine tests, of hypothyroidism (AIH) and hyperthyroidism expressed as: type I amiodarone induced thyrotoxicosis (AIT I), type II amiodarone induced thyrotoxicosis (AIT II), and less frequently as a mixt form, type III amiodarone induced thyrotoxicosis (AIT III). We presented cases from the database of a tertiary center in Cluj-Napoca, Romania. Despite the frequent complication of thyroid function, this pathology is underestimated and diagnosed. There is a limited number of studies and clear protocols, especially in the mixed forms cases. This increase in iodine uptake interferes seriously with thyroid hormone production and release. The nuclear medicine tests are essential in the correct assessment and differential diagnosis of different forms of induced thyroid dysfunction. The destruction of the follicular cells can result in the release of excessive thyroid hormone into the circulation, with potential development of atrial fibrillation, worsening the cardiac disease, so any benefic therapeutic procedure should be known; the use of radioiodine as therapy alternative, despite the known limitations induced by blockade was clear benefic in the case presented. A special attention needs to be addressed to those patients with differentiated thyroid cancer, which will be submitted to radioiodine therapy and are under chronic therapy with amiodarone. The nuclear medicine procedures are essential in the correct assessment and differential diagnosis of different forms of induced thyroid dysfunction. The radioiodine is not recommended in AIT, due to stunning effect induced by iodine excess, but in some special, lifethreatening condition, radioiodine I-131 might be a treatment option. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Iodine distribution in natural waters of different chemical composition in relation to water-bearing soils and rocks and water fractions in areas subjected to radioiodine contamination

NASA Astrophysics Data System (ADS)

Kolmykova, Liudmila; Korobova, Elena

2017-04-01

Iodine is an essential microelement required for normal functioning of thyroid gland. Natural deficiency of stable iodine is compensated by its active intake by thyroid and provokes its higher irradiation in case of radiation accidents and contamination of the environment by radioiodine isotopes. The bioavailability of both stable and radioactive iodine and the specificity of its uptake by living organisms largely depends on geochemical parameters of the environment related to natural conditions of water migration. The goal of the study was to investigate spatial distribution of iodine in natural water of different chemical composition in relation to typical water-bearing soils and rocks and water fractions in Bryansk areas subjected to radioiodine contamination after the Chernobyl accident and to evaluate contribution of this factor to the occurrence of endemic thyroid diseases among local population inhabiting geochemically different areas of fluvioglacial and loess-like sedimentary rocks. The highest content of iodine (Me=13.3 µg/l) was observed in surface water of landscapes with H-Ca, Ca and H-Ca-Fe classes of water migration. The lowest microelement level (Me=5.25 µg/l) was noted in groundwater of landscapes with H, H-Fe classes of water migration in areas of Paleogene water bearing rocks. Regardless of the type of source and class of water migration up to 90% of the total content of iodide is present in the fraction <0.45 µm (as determined by membrane filtration). Up to 50% of iodine pass to solution containing particles < 0.1 µm and increases up to 80% in absence of roughly dispersed sorbents in this fraction. The surface water in areas of loess-like sedimentary rocks hosts the highest levels of iodine where its associated with calcium mineral aquatic complexes and the suspended particles. The obtained data is believed to be useful in explanation of mobility and intake of iodine and its radioactive analogues by rural population living in different geochemical conditions and using local drinking waters. The data should be accounted of in planning prophylactics of endemic diseases and counter measures in case of radioiodine fallout.

Chemical composition of drinking water as a possible environment-specific factor modifying the thyroid risk in the areas subjected to radioiodine contamination

NASA Astrophysics Data System (ADS)

Kolmykova, Lyudmila; Korobova, Elena; Ryzhenko, Boris

2015-04-01

Water is one of the main natural agents providing chemical elements' migration in the environment and food chains. In our opinion a study of spatial variation of the essential trace elements in local drinking water is worth considering as the factor that may contribute to variation of the health risk in areas contaminated by radionuclides and radioiodine in particular. Radioiodine was proved to increase the risk of thyroid cancer among children who lived in areas contaminated during the Chernobyl accident. It was also shown that low stable iodine status of the contaminated area and population also contributed to the risk of this disease in case of radionuclide contamination. The goal of the study was to investigate chemical composition of the drinking water in rural settlements of the Bryansk oblast' subjected to radioiodine contamination and to evaluate speciation of stable I and Se on the basis of their total concentration and chemical composition of the real water samples with the help of thermodynamic modelling. Water samples were collected from different aquifers discharging at different depths (dug wells, local private bore holes and water pipes) in rural settlements located in areas with contrasting soil iodine status. Thermodynamic modelling was performed using original software (HCh code of Y.Shvarov, Moscow State University, RUSSIA) incorporating the measured pH, Corg and elements' concentration values. Performed modelling showed possibility of formation of complex CaI+ ion in aqueous phase, I sorption by goethite and transfer of Se to solid phase as FeSe in the observed pH-Eh conditions. It helped to identify environmental conditions providing high I and Se mobility and their depletion from natural waters. Both the experimental data and modeling showed that I and Se migration and deficiency in natural water is closely connected to pH, Eh conditions and the concentration of typomorphic chemical elements (Ca, Mg, Fe) defining the class of water migration in landscapes (according Perel'man, 1975). Obtained data will be used for evaluation of contribution of I and Se status of drinking water to the risk of thyroid diseases among local population.

The management of metastatic radioiodine-refractory differentiated thyroid cancer requires an integrated approach including both directed and systemic therapies.

PubMed

Cooray, Shamil D; Topliss, Duncan J

2017-01-01

A 58-year-old man with metastatic radioiodine-refractory differentiated thyroid cancer (DTC) presented with left thigh and right flank numbness. He had known progressive and widespread bony metastases, for which he received palliative radiotherapy, and multiple bilateral asymptomatic pulmonary metastases. CT scan and MRI of the spine revealed metastases at right T10-L1 vertebrae with extension into the central canal and epidural disease at T10 and T11 causing cord displacement and canal stenosis but retention of spinal cord signal. Spinal surgery was followed by palliative radiotherapy resulting in symptom resolution. Two months later, sorafenib received approval for use in Australia and was commenced and up-titrated with symptomatic management of mild adverse effects. Follow-up CT scan three months after commencement of sorafenib revealed regression of pulmonary metastases but no evident change in most bone metastases except for an advancing lesion eroding into the right acetabulum. The patient underwent a right total hip replacement, intra-lesional curettage and cementing. After six months of sorafenib therapy, CT scanning showed enlarging liver lesions with marked elevation of serum thyroglobulin. Lenvatinib was commenced and sorafenib was ceased. He now has stable disease with a falling thyroglobulin more than 5 years after metastatic radioiodine-refractory DTC was diagnosed. In DTC, 5% of distant metastases become radioiodine-refractory, resulting in a median overall survival of 2.5-3.5 years. Tyrosine kinase inhibitor (TKI) therapy has recently been demonstrated to increase progression-free survival in these patients but poses some unique management issues and is best used as part of an integrated approach with directed therapy. Directed therapies may have greater potential to control localised disease and related symptoms when compared to systemic therapies.Consider TKI therapy in progressive disease where benefits outweigh risks.Active surveillance and timely intervention are required for TKI-related adverse effects.There is a need for further research on the clinical application of TKI therapy in advanced DTC, including comparative efficacy, sequencing and identifying responders.

On the role of the gut in diabetic hyperglucagonaemia.

PubMed

Lund, Asger

2017-04-01

Patients with type 2 diabetes are characterised not only by compromised insulin secretion and action, but also by elevated plasma concentrations of the 29-amino acid peptide hormone glucagon, which generally is thought of as a pancreas-derived hormone (produced in and secreted from alpha cells in the islet of Langerhans). In patients with diabetes, circulating glucagon concentrations are elevated in the fasting state and fail to decrease appropriately or even increase in response to ingestion of nutrients. Glucagon is known to be a potent stimulator of hepatic glucose production, and, thus, the elevated glucagon concentrations in diabetes contribute decisively to the predominating trait of patients with diabetes namely hyperglycaemia. Interestingly, studies have shown that while oral intake of glucose results in inappropriately high plasma concentrations of glucagon in patients with diabetes, intravenous (iv) infusion of glucose does not. The mechanisms behind these differential glucagon responses to oral vs. iv glucose administration are currently unexplained. Three hypotheses were tested in the present thesis: 1) Could the inappropriate glucagon response to oral glucose ingestion in patients with diabetes be attributed to the release of glucagonotropic/glucagonostatic peptides secreted from the gut? 2) Could the inappropriate glucagon response to oral glucose ingestion in diabetes be a result of extrapancreatic glucagon secretion (possibly originating from the gut)? And 3) Does the differential glucagon responses between oral and iv glucose administration affect endogenous glucose production (EGP). The overall aim of this PhD thesis was, thus, to investigate the role of the gut in diabetic hyperglucagonaemia and hyperglycaemia. In Study I we examined the effect of the three gut-derived hormones glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) on glucagon secretion in patients with type 2 diabetes. We applied a 50 g-oral glucose tolerance test (OGTT), and five isoglycaemic iv glucose infusions (IIGIs) with either saline, GIP, GLP-1, GLP-2 or a combination of the three hormones. We show that these gut-derived hormones affect glucagon secretion differently and that OGTT-induced secretion of these hormones may play a role in the inappropriate glucagon response to orally ingested glucose in patients with type 2 diabetes with especially GIP acting to increase glucagon secretion. In Study II we examined totally pancreatectomised patients and non-diabetic control subjects during a 75 g-OGTT and an IIGI. We applied sandwich enzyme-linked immunosorbent assay (ELISA) and mass spectrometry-based proteomics for plasma glucagon analysis and show that 29-amino acid glucagon circulates in patients without a pancreas and that glucose stimulation of the gut results in significant hyperglucagonemia in these patients - ultimately confirming the existence of extrapancreatic glucagon secretion in humans. In Study III we examined whether the different responses of insulin and glucagon, respectively, between oral and iv glucose administration translate into differences in EGP and glucose disappearance in patients with type 2 diabetes and non-diabetic control subjects. We applied glucose tracer methodology during a 75 g-OGTT, IIGI and IIGI + iv glucagon (to isolate the effect of glucagon) and show that EGP is less suppressed during OGTT than during IIGI in both patients with type 2 diabetes and non-diabetic control subjects. Articles published in the Danish Medical Journal are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

Dynamic modeling of the hydrogel molecular filter in a metamaterial biosensing system for glucose concentration estimation.

PubMed

Teutsch, T; Mesch, M; Giessen, H; Tarin, C

2014-01-01

We present a novel concept for ophthalmic glucose sensing using a biosensing system that consists of plasmonic dipole metamaterial covered by a layer of functionalized hydrogel. The metamaterial together with the hydrogel can be integrated into a contact lens. This optical sensor changes its properties such as reflectivity upon the ambient glucose concentration, which allows in situ measurements in the eye. The functionalization of the sensor with hydrogel allows for a glucose-specific detection, providing both selectivity and sensitivity. As a result of the presented work we derive a dynamic model of the hydrogel that can be used for further simulation studies.

Establishing a synergetic carbon utilization mechanism for non-catabolic use of glucose in microbial synthesis of trehalose.

PubMed

Wu, Yifei; Sun, Xinxiao; Lin, Yuheng; Shen, Xiaolin; Yang, Yaping; Jain, Rachit; Yuan, Qipeng; Yan, Yajun

2017-01-01

In nature glucose is a common carbon and energy source for catabolic use and also a building unit of polysaccharides and glycosylated compounds. The presence of strong glucose catabolic pathways in microorganism rapidly decomposes glucose into smaller metabolites and challenges non-catabolic utilization of glucose as C6 building unit or precursor. To address this dilemma, we design a synergetic carbon utilization mechanism (SynCar), in which glucose catabolism is inactivated and a second carbon source (e.g. glycerol) is employed to maintain cell growth and rationally strengthen PEP driving force for glucose uptake and non-catabolic utilization. Remarkably, a trehalose biosynthesis model developed for proof-of-concept indicates that SynCar leads to 131% and 200% improvement in trehalose titer and yield, respectively. The conversion rate of glucose to trehalose reaches 91% of the theoretical maximum. This work demonstrates the broad applicability of SynCar in the biosynthesis of molecules derived from non-catabolic glucose. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Quality changes in refrigerated stored minced pork wrapped with plastic cling film and the effect of glucose supplementation.

PubMed

Del Blanco, Alba; Caro, Irma; Quinto, Emiliano J; Mateo, Javier

2017-04-01

Meat spoilage greatly depends on meat composition and storage conditions. Microbial and biochemical changes in minced pork (100-g portions) wrapped with a polyvinyl chloride film during a 4-day refrigerated storage were studied. As glucose is the first substrate used by spoilage bacteria and when it is depleted bacteria could generate undesirable volatiles, the effect of the addition of glucose to minced meat was also studied. Three treatments were used: control (C), without added glucose, and low and high glucose concentration (L and H), 150mg and 750mg of glucose in 100g of meat, respectively. Spoilage bacteria, pH, redox potential, colour, basic volatile nitrogen, glucose, organic acids, and volatiles were analyzed in both recently prepared and stored pork samples. Storage resulted in increased levels of lactic acid bacteria and glucose-derived short chain alkyl volatiles, and a decrease in redox potential and volatile aldehyde levels. The addition of glucose to meat did not affect the biochemical characteristics of stored minced pork. Copyright © 2016 Elsevier Ltd. All rights reserved.

Restoration of euglycemia after duodenal bypass surgery is reliant on central and peripheral inputs in Zucker fa/fa rats.

PubMed

Jiao, Jian; Bae, Eun Ju; Bandyopadhyay, Gautam; Oliver, Jason; Marathe, Chaitra; Chen, Michael; Hsu, Jer-Yuan; Chen, Yu; Tian, Hui; Olefsky, Jerrold M; Saberi, Maziyar

2013-04-01

Gastrointestinal bypass surgeries that result in rerouting and subsequent exclusion of nutrients from the duodenum appear to rapidly alleviate hyperglycemia and hyperinsulinemia independent of weight loss. While the mechanism(s) responsible for normalization of glucose homeostasis remains to be fully elucidated, this rapid normalization coupled with the well-known effects of vagal inputs into glucose homeostasis suggests a neurohormonally mediated mechanism. Our results show that duodenal bypass surgery on obese, insulin-resistant Zucker fa/fa rats restored insulin sensitivity in both liver and peripheral tissues independent of body weight. Restoration of normoglycemia was attributable to an enhancement in key insulin-signaling molecules, including insulin receptor substrate-2, and substrate metabolism through a multifaceted mechanism involving activation of AMP-activated protein kinase and downregulation of key regulatory genes involved in both lipid and glucose metabolism. Importantly, while central nervous system-derived vagal nerves were not essential for restoration of insulin sensitivity, rapid normalization in hepatic gluconeogenic capacity and basal hepatic glucose production required intact vagal innervation. Lastly, duodenal bypass surgery selectively altered the tissue concentration of intestinally derived glucoregulatory hormone peptides in a segment-specific manner. The present data highlight and support the significance of vagal inputs and intestinal hormone peptides toward normalization of glucose and lipid homeostasis after duodenal bypass surgery.

Anaerobic consumers of monosaccharides in a moderately acidic fen.

PubMed

Hamberger, Alexandra; Horn, Marcus A; Dumont, Marc G; Murrell, J Colin; Drake, Harold L

2008-05-01

16S rRNA-based stable isotope probing identified active xylose- and glucose-fermenting Bacteria and active Archaea, including methanogens, in anoxic slurries of material obtained from a moderately acidic, CH(4)-emitting fen. Xylose and glucose were converted to fatty acids, CO(2), H(2), and CH(4) under moderately acidic, anoxic conditions, indicating that the fen harbors moderately acid-tolerant xylose- and glucose-using fermenters, as well as moderately acid-tolerant methanogens. Organisms of the families Acidaminococcaceae, Aeromonadaceae, Clostridiaceae, Enterobacteriaceae, and Pseudomonadaceae and the order Actinomycetales, including hitherto unknown organisms, utilized xylose- or glucose-derived carbon, suggesting that highly diverse facultative aerobes and obligate anaerobes contribute to the flow of carbon in the fen under anoxic conditions. Uncultured Euryarchaeota (i.e., Methanosarcinaceae and Methanobacteriaceae) and Crenarchaeota species were identified by 16S rRNA analysis of anoxic slurries, demonstrating that the acidic fen harbors novel methanogens and Crenarchaeota organisms capable of anaerobiosis. Fermentation-derived molecules are conceived to be the primary drivers of methanogenesis when electron acceptors other than CO(2) are absent, and the collective findings of this study indicate that fen soils harbor diverse, acid-tolerant, and novel xylose-utilizing as well as glucose-utilizing facultative aerobes and obligate anaerobes that form trophic links to novel moderately acid-tolerant methanogens.

Synthesis and characterization of carbon nanospheres obtained by hydrothermal carbonization of wood-derived and other saccharides

Treesearch

Qiangu Yan; Rui Li; Hossein Toghiani; Zhiyong Cai; Jilei Zhang

2015-01-01

Carbon nanospheres were synthesized by hydrothermal carbonization (HTC) of four different carbon sources: xylose, glucose, sucrose, and pine wood derived saccharides. The obtained carbon nanospheres were characterized for particle morphology and size, and surface functional groups. Morphological and structural differences among these saccharides derived HTC carbons...

Docosahexaenoyl ethanolamide improves glucose uptake and alters endocannabinoid system gene expression in proliferating and differentiating C2C12 myoblasts

PubMed Central

Kim, Jeffrey; Carlson, Morgan E.; Watkins, Bruce A.

2014-01-01

Skeletal muscle is a major storage site for glycogen and a focus for understanding insulin resistance and type-2-diabetes. New evidence indicates that overactivation of the peripheral endocannabinoid system (ECS) in skeletal muscle diminishes insulin sensitivity. Specific n-6 and n-3 polyunsaturated fatty acids (PUFA) are precursors for the biosynthesis of ligands that bind to and activate the cannabinoid receptors. The function of the ECS and action of PUFA in skeletal muscle glucose uptake was investigated in proliferating and differentiated C2C12 myoblasts treated with either 25 μM of arachidonate (AA) or docosahexaenoate (DHA), 25 μM of EC [anandamide (AEA), 2-arachidonoylglycerol (2-AG), docosahexaenoylethanolamide (DHEA)], 1 μM of CB1 antagonist NESS0327, and CB2 inverse agonist AM630. Compared to the BSA vehicle control cell cultures in both proliferating and differentiated myoblasts those treated with DHEA, the EC derived from the n-3 PUFA DHA, had higher 24 h glucose uptake, while AEA and 2-AG, the EC derived from the n-6 PUFA AA, had lower basal glucose uptake. Adenylyl cyclase mRNA was higher in myoblasts treated with DHA in both proliferating and differentiated states while those treated with AEA or 2-AG were lower compared to the control cell cultures. Western blot and qPCR analysis showed higher expression of the cannabinoid receptors in differentiated myoblasts treated with DHA while the opposite was observed with AA. These findings indicate a compensatory effect of DHA and DHEA compared to AA-derived ligands on the ECS and associated ECS gene expression and higher glucose uptake in myoblasts. PMID:24711795

Measurement of gluconeogenesis using glucose fragments and mass spectrometry after ingestion of deuterium oxide.

PubMed

Chacko, Shaji K; Sunehag, Agneta L; Sharma, Susan; Sauer, Pieter J J; Haymond, Morey W

2008-04-01

We report a new method to measure the fraction of glucose derived from gluconeogenesis using gas chromatography-mass spectrometry and positive chemical ionization. After ingestion of deuterium oxide by subjects, glucose derived from gluconeogenesis is labeled with deuterium. Our calculations of gluconeogenesis are based on measurements of the average enrichment of deuterium on carbon 1, 3, 4, 5, and 6 of glucose and the deuterium enrichment in body water. In a sample from an adult volunteer after ingestion of deuterium oxide, fractional gluconeogenesis using the "average deuterium enrichment method" was 48.3 +/- 0.5% (mean +/- SD) and that with the C-5 hexamethylenetetramine (HMT) method by Landau et al. (Landau BR, Wahren J, Chandramouli V, Schumann WC, Ekberg K, Kalhan SC; J Clin Invest 98: 378-385, 1996) was 46.9 +/- 5.4%. The coefficient of variation of 10 replicate analyses using the new method was 1.0% compared with 11.5% for the C-5 HMT method. In samples derived from an infant receiving total parenteral nutrition, fractional gluconeogenesis was 13.3 +/- 0.3% using the new method and 13.7 +/- 0.8% using the C-5 HMT method. Fractional gluconeogenesis measured in six adult volunteers after 66 h of continuous fasting was 83.7 +/- 2.3% using the new method and 84.2 +/- 5.0% using the C-5 HMT method. In conclusion, the average deuterium enrichment method is simple, highly reproducible, and cost effective. Furthermore, it requires only small blood sample volumes. With the use of an additional tracer, glucose rate of appearance can also be measured during the same analysis. Thus the new method makes measurements of gluconeogenesis available and affordable to large numbers of investigators under conditions of low and high fractional gluconeogenesis ( approximately 10 to approximately 90) in all subject populations.

Cerebral glucose metabolism and the glutamine cycle as detected by in vivo and in vitro 13C NMR spectroscopy.

PubMed

García-Espinosa, María A; Rodrigues, Tiago B; Sierra, Alejandra; Benito, Marina; Fonseca, Carla; Gray, Heather L; Bartnik, Brenda L; García-Martín, María L; Ballesteros, Paloma; Cerdán, Sebastián

2004-01-01

We review briefly 13C NMR studies of cerebral glucose metabolism with an emphasis on the roles of glial energetics and the glutamine cycle. Mathematical modeling analysis of in vivo 13C turnover experiments from the C4 carbons of glutamate and glutamine are consistent with: (i) the glutamine cycle being the major cerebral metabolic route supporting glutamatergic neurotransmission, (ii) glial glutamine synthesis being stoichiometrically coupled to glycolytic ATP production, (iii) glutamine serving as the main precursor of neurotransmitter glutamate and (iv) glutamatergic neurotransmission being supported by lactate oxidation in the neurons in a process accounting for 60-80% of the energy derived from glucose catabolism. However, more recent experimental approaches using inhibitors of the glial tricarboxylic acid (TCA) cycle (trifluoroacetic acid, TFA) or of glutamine synthase (methionine sulfoximine, MSO) reveal that a considerable portion of the energy required to support glutamine synthesis is derived from the oxidative metabolism of glucose in the astroglia and that a significant amount of the neurotransmitter glutamate is produced from neuronal glucose or lactate rather than from glial glutamine. Moreover, a redox switch has been proposed that allows the neurons to use either glucose or lactate as substrates for oxidation, depending on the relative availability of these fuels under resting or activation conditions, respectively. Together, these results suggest that the coupling mechanisms between neuronal and glial metabolism are more complex than initially envisioned.

Interaction between Marine-Derived n-3 Long Chain Polyunsaturated Fatty Acids and Uric Acid on Glucose Metabolism and Risk of Type 2 Diabetes Mellitus: A Case-Control Study.

PubMed

Li, Kelei; Wu, Kejian; Zhao, Yimin; Huang, Tao; Lou, Dajun; Yu, Xiaomei; Li, Duo

2015-08-26

The present case-control study explored the interaction between marine-derived n-3 long chain polyunsaturated fatty acids (n-3 LC PUFAs) and uric acid (UA) on glucose metabolism and risk of type 2 diabetes mellitus (T2DM). Two hundred and eleven healthy subjects in control group and 268 T2DM subjects in case group were included. Plasma phospholipid (PL) fatty acids and biochemical parameters were detected by standard methods. Plasma PL C22:6n-3 was significantly lower in case group than in control group, and was negatively correlated with fasting glucose (r = -0.177, p < 0.001). Higher plasma PL C22:6n-3 was associated with lower risk of T2DM, and the OR was 0.32 (95% confidence interval (CI), 0.12 to 0.80; p = 0.016) for per unit increase of C22:6n-3. UA was significantly lower in case group than in control group. UA was positively correlated with fasting glucose in healthy subjects, but this correlation became negative in T2DM subjects. A significant interaction was observed between C22:6n-3 and UA on fasting glucose (p for interaction = 0.005): the lowering effect of C22:6n-3 was only significant in subjects with a lower level of UA. In conclusion, C22:6n-3 interacts with UA to modulate glucose metabolism.

[Radioiodine treatment of Graves' disease --for its wider indication and application in Japan].

PubMed

Konishi, Junji

2006-12-01

Radioiodine treatment has been well established as an effective and safe therapeutic modality for Graves' disease. To promote more efficient use of this treatment in Japan, a working group has been organized in the Japan Thyroid Association and preparation of guidelines for its clinical use is under way. The treatment using upto 13.5 mCi of I-131 is feasible on out-patient basis. In comparison to the antithyroid drug treatment, the treatment has no side effects, brings in good control of hyperthyroidism and decrease the size of goiter. It is contraindicated in pregnant and lactating women. Patients treated should be carefully monitored for the possible worsening of ophthalmopathy and neonatal Graves' disease. Recent studies revealed the cost-effectiveness of the treatment. Its application to autonomously functioning thyroid nodules and toxic multinodular goiters is also discussed.

A convenient Simple Method for Synthesis of Meta-iodobenzylguanidine (MIBG).

PubMed

Sheikholislam, Zahra; Soleimani, Zohreh; Moghimi, Abolghasem; Shahhosseini, Soraya

2013-01-01

Radioiodinated meta-iodobenzylguanidine (MIBG) is one of the important radiopharmaceuticals in Nuclear Medicine. [(123/131)I] MIBG is used for imaging of Adrenal medulla, studying heart sympathetic nerves, treatment of pheochromacytoma and neuroblastoma. For clinical application, radioiodinated MIBG is prepared through isotopic exchange method, which includes replacement of radioactive iodine in a nucleophilic substitution reaction with cold iodine ((127)I). The unlabelled MIBG hemisulfate is synthesized by the procedure described by Wieland et al. (1980). The availability of a more practical and cost-effective procedure for MIBG preparation encouraged us to study the MIBG synthesis methods. In this study the preparation of MIBG through different methods were evaluated and a new method, which is one step, simple and cost-effective is introduced. The method has ability to be scaled up for production of unlabelled MIBG.

Effect of specific activity on cardiac uptake of iodine-123-MIBG.

PubMed

Farahati, J; Bier, D; Scheubeck, M; Lassmann, M; Schelper, L F; Grelle, I; Hanscheid, H; Biko, J; Graefe, K H; Reiners, C

1997-03-01

Radioiodinated meta-iodobenzylguanidine (MIBG), an analog of norepinephrine, has been used to assess myocardial sympathetic innervation. Recent in vivo studies predict enhanced cardiac uptake of this radiopharmaceutical with high specific activity. To clarify the effect of specific activity on cardiac uptake of radioiodinated MIBG, the distribution and kinetics of no-carrier-added [123I]MIBG (> or = 7.4 TBq/mumol) were compared with those of commercial [123I]MIBG (approximately 74 MBq/mumol) in three healthy volunteers by serial imaging and blood sampling. Higher specific activity result in higher uptake of radioiodinated MIBG in all volunteers in the heart (p < 0.05) and liver (p < 0.05) but not in the lung (p = 0.26). Due to rapid deiodination, a more pronounced accumulation of radioactivity was present in plasma after no-carrier-added MIBG than commercial [123I]MIBG, resulting in higher background and thyroid activity after administration of the former. Calculated heart-to-liver (p = 0.96) and heart-to-lung (p = 0.42) count ratios in all volunteers revealed no significant improvement in cardiac imaging with no-carrier-added [123I]MIBG compared to commercial [123I]MIBG. This study highlights the appreciably higher in vivo deiodination of no-carrier-added [123I]MIBG compared to commercial preparation of [123I]MIBG in humans. Cardiac images acquired with no-carrier-added [123I]MIBG do not seem to be superior to those obtained with commercial MIBG.

Influence of nano-fibrillated cellulose (NFC) on starch digestion and glucose absorption.

PubMed

Liu, Lingling; Kerr, William L; Kong, Fanbin; Dee, Derek R; Lin, Mengshi

2018-09-15

Nano-fibrillated cellulose (NFC) is of interest in several fields due to its unique physical properties derived from its nanoscale dimensions. NFC has potential use in food systems as a dietary fiber that increases viscosity and limit diffusion of glucose. This study focused on the effects of added NFC on solution viscosity, starch digestion and glucose absorption. NFC did not affect α-amylase and α-glucosidase activity, but significantly retarded glucose diffusion, delayed amylolysis and reduced the amount of glucose released during in vitro digestion of starch. Specifically, 1% NFC retarded ∼26.6% of glucose released during the amylolysis process. The greatly increased viscosity of NFC at concentrations >0.5% was thought to be the main mechanism for its potential hypoglycemic effects. NFC suspensions also had higher glucose adsorption capacity than those containing cellulose. In addition, NFC bound 35.6% of the glucose when the initial glucose level was within the range of 5-200 mM. These results suggest that NFC may be useful for building viscosity in food products and serving to inhibit glucose absorption in vivo in starch-containing products. Copyright © 2018 Elsevier Ltd. All rights reserved.

Lung Dosimetry for Radioiodine Treatment Planning in the Case of Diffuse Lung Metastases

PubMed Central

Song, Hong; He, Bin; Prideaux, Andrew; Du, Yong; Frey, Eric; Kasecamp, Wayne; Ladenson, Paul W.; Wahl, Richard L.; Sgouros, George

2010-01-01

The lungs are the most frequent sites of distant metastasis in differentiated thyroid carcinoma. Radioiodine treatment planning for these patients is usually performed following the Benua– Leeper method, which constrains the administered activity to 2.96 GBq (80 mCi) whole-body retention at 48 h after administration to prevent lung toxicity in the presence of iodine-avid lung metastases. This limit was derived from clinical experience, and a dosimetric analysis of lung and tumor absorbed dose would be useful to understand the implications of this limit on toxicity and tumor control. Because of highly nonuniform lung density and composition as well as the nonuniform activity distribution when the lungs contain tumor nodules, Monte Carlo dosimetry is required to estimate tumor and normal lung absorbed dose. Reassessment of this toxicity limit is also appropriate in light of the contemporary use of recombinant thyrotropin (thyroid-stimulating hormone) (rTSH) to prepare patients for radioiodine therapy. In this work we demonstrated the use of MCNP, a Monte Carlo electron and photon transport code, in a 3-dimensional (3D) imaging–based absorbed dose calculation for tumor and normal lungs. Methods A pediatric thyroid cancer patient with diffuse lung metastases was administered 37MBq of 131I after preparation with rTSH. SPECT/CT scans were performed over the chest at 27, 74, and 147 h after tracer administration. The time–activity curve for 131I in the lungs was derived from the whole-body planar imaging and compared with that obtained from the quantitative SPECT methods. Reconstructed and coregistered SPECT/CT images were converted into 3D density and activity probability maps suitable for MCNP4b input. Absorbed dose maps were calculated using electron and photon transport in MCNP4b. Administered activity was estimated on the basis of the maximum tolerated dose (MTD) of 27.25 Gy to the normal lungs. Computational efficiency of the MCNP4b code was studied with a simple segmentation approach. In addition, the Benua–Leeper method was used to estimate the recommended administered activity. The standard dosing plan was modified to account for the weight of this pediatric patient, where the 2.96-GBq (80 mCi) whole-body retention was scaled to 2.44 GBq (66 mCi) to give the same dose rate of 43.6 rad/h in the lungs at 48 h. Results Using the MCNP4b code, both the spatial dose distribution and a dose–volume histogram were obtained for the lungs. An administered activity of 1.72 GBq (46.4 mCi) delivered the putative MTD of 27.25 Gy to the lungs with a tumor absorbed dose of 63.7 Gy. Directly applying the Benua–Leeper method, an administered activity of 3.89 GBq (105.0 mCi) was obtained, resulting in tumor and lung absorbed doses of 144.2 and 61.6 Gy, respectively, when the MCNP-based dosimetry was applied. The voxel-by-voxel calculation time of 4,642.3 h for photon transport was reduced to 16.8 h when the activity maps were segmented into 20 regions. Conclusion MCNP4b–based, patient-specific 3D dosimetry is feasible and important in the dosimetry of thyroid cancer patients with avid lung metastases that exhibit prolonged retention in the lungs. PMID:17138741

Emerging role of the brain in the homeostatic regulation of energy and glucose metabolism.

PubMed

Roh, Eun; Song, Do Kyeong; Kim, Min-Seon

2016-03-11

Accumulated evidence from genetic animal models suggests that the brain, particularly the hypothalamus, has a key role in the homeostatic regulation of energy and glucose metabolism. The brain integrates multiple metabolic inputs from the periphery through nutrients, gut-derived satiety signals and adiposity-related hormones. The brain modulates various aspects of metabolism, such as food intake, energy expenditure, insulin secretion, hepatic glucose production and glucose/fatty acid metabolism in adipose tissue and skeletal muscle. Highly coordinated interactions between the brain and peripheral metabolic organs are critical for the maintenance of energy and glucose homeostasis. Defective crosstalk between the brain and peripheral organs contributes to the development of obesity and type 2 diabetes. Here we comprehensively review the above topics, discussing the main findings related to the role of the brain in the homeostatic regulation of energy and glucose metabolism.

Emerging role of the brain in the homeostatic regulation of energy and glucose metabolism

PubMed Central

Roh, Eun; Song, Do Kyeong; Kim, Min-Seon

2016-01-01

Accumulated evidence from genetic animal models suggests that the brain, particularly the hypothalamus, has a key role in the homeostatic regulation of energy and glucose metabolism. The brain integrates multiple metabolic inputs from the periphery through nutrients, gut-derived satiety signals and adiposity-related hormones. The brain modulates various aspects of metabolism, such as food intake, energy expenditure, insulin secretion, hepatic glucose production and glucose/fatty acid metabolism in adipose tissue and skeletal muscle. Highly coordinated interactions between the brain and peripheral metabolic organs are critical for the maintenance of energy and glucose homeostasis. Defective crosstalk between the brain and peripheral organs contributes to the development of obesity and type 2 diabetes. Here we comprehensively review the above topics, discussing the main findings related to the role of the brain in the homeostatic regulation of energy and glucose metabolism. PMID:26964832

Exosomes derived from high-glucose-stimulated Schwann cells promote development of diabetic peripheral neuropathy.

PubMed

Jia, Longfei; Chopp, Michael; Wang, Lei; Lu, Xuerong; Szalad, Alexandra; Zhang, Zheng Gang

2018-06-22

Schwann cells actively interact with axons of dorsal root ganglia (DRG) neurons. Exosomes mediate intercellular communication by transferring their biomaterials, including microRNAs (miRs) into recipient cells. We hypothesized that exosomes derived from Schwann cells stimulated by high glucose (HG) exosomes accelerate development of diabetic peripheral neuropathy and that exosomal cargo miRs contribute to this process. We found that HG exosomes contained high levels of miR-28, -31a, and -130a compared to exosomes derived from non-HG-stimulated Schwann cells. In vitro, treatment of distal axons with HG exosomes resulted in reduction of axonal growth, which was associated with elevation of miR-28, -31a, and -130a and reduction of their target proteins of DNA methyltransferase-3α, NUMB (an endocytic adaptor protein), synaptosome associated protein 25, and growth-associated protein-43 in axons. In vivo, administration of HG exosomes to sciatic nerves of diabetic db/db mice at 7 wk of age promoted occurrence of peripheral neuropathy characterized by impairment of nerve conduction velocity and induction of mechanic and thermal hypoesthesia, which was associated with substantial decreases in intraepidermal nerve fibers. Our findings demonstrate a functional role of exosomes derived from HG-stimulated Schwann cells in mediating development of diabetic peripheral neuropathy.-Jia, L., Chopp, M., Wang, L., Lu, X., Szalad, A., Zhang, Z. G. Exosomes derived from high-glucose-stimulated Schwann cells promote development of diabetic peripheral neuropathy.

[Sex hormones and the metabolism of carbohydrates].

PubMed

Boukhris, R

1987-12-01

Sex hormones play an important role in the control of glucose metabolism and insulin. Decreased glucose tolerance observed at the end of pregnancy in most cases remains within normal limits. Pregnancy has an important effect on the islets of Langerhans and on the growth of beta cellules. At the end of pregnancy, assimilation of glucose and triglycerides by maternal tissues is slowed and transfer to the fetus is favored. Hyperinsulinism persists but insulin resistance at the level of maternal tissue becomes very strong and the number of receptors declines. This late pregnancy insulin resistance has not been satisfactorily explained. The declining number of receptors may be a mechanism, or the "antiinsulin" pregnancy hormones which includes estrogens and progesterone may play a major role. Although other mechanisms have been proposed to explain the antiinsulin effect, the role of sex hormones and especially of progesterone (and synthetic progestins used in contraception) appears crucial. The presence of estrogen and progesterone receptors in the beta cellules of the islets of Langerhans suggests a direct effect of these hormones on the cellules. Estrogens however work by other mechanisms than insulin secretion. Experimental evidence indicates that during pregnancy, progesterone increases insulin release while human placental lactogen stimulates hyperplasia of the islets. The progestins derived from progesterone used in contraception have a parallel action. A slight elevation of blood sugar and insulinemia have been observed in oral contraceptive (OC) users. Only 3-5% of OC users develop true hyperglycemia. The changes are usually transitory and disappear on termination of OC use except in the small number of women predisposed to diabetes. The decreased glucose tolerance of OC users differs from true diabetes. Combined OCs favor vascular accidents and myocardial infarct in insulin-dependent diabetics. The mechanisms involved include deteriorating control of diabetes; effects on the serum lipids, coagulation factors, and blood pressure; and direct effects of estrogen on the vascular wall. Venous but not arterial vascular accidents decline with lower estrogen doses. Progestins probably play a more significant role from estrogens in decreasing glucose tolerance. Pregnanes, progestins derived from progesterone, do not appear to affect glucose tolerance. Among testosterone derivatives, the entrances decrease glucose tolerance slightly and the gonanes more strongly, also causing hyperinsulinism. But the new triphasic OCs with low levonorgestrel doses cause no significant changes in glucose tolerance even in women with histories of gestational diabetes. Long-acting progestin implants, vaginal rings, and injectables appear thus far to have minimal or no effects on glucose tolerance.

How does cellulosome composition influence deconstruction of lignocellulosic substrates in Clostridium (Ruminiclostridium) thermocellum DSM 1313?

PubMed

Yoav, Shahar; Barak, Yoav; Shamshoum, Melina; Borovok, Ilya; Lamed, Raphael; Dassa, Bareket; Hadar, Yitzhak; Morag, Ely; Bayer, Edward A

2017-01-01

Bioethanol production processes involve enzymatic hydrolysis of pretreated lignocellulosic biomass into fermentable sugars. Due to the relatively high cost of enzyme production, the development of potent and cost-effective cellulolytic cocktails is critical for increasing the cost-effectiveness of bioethanol production. In this context, the multi-protein cellulolytic complex of Clostridium ( Ruminiclostridium ) thermocellum, the cellulosome, was studied here. C. thermocellum is known to assemble cellulosomes of various subunit (enzyme) compositions, in response to the available carbon source. In the current study, different carbon sources were used, and their influence on both cellulosomal composition and the resultant activity was investigated. Glucose, cellobiose, microcrystalline cellulose, alkaline-pretreated switchgrass, alkaline-pretreated corn stover, and dilute acid-pretreated corn stover were used as sole carbon sources in the growth media of C. thermocellum strain DSM 1313. The purified cellulosomes were compared for their activity on selected cellulosic substrates. Interestingly, cellulosomes derived from cells grown on lignocellulosic biomass showed no advantage in hydrolyzing the original carbon source used for their production. Instead, microcrystalline cellulose- and glucose-derived cellulosomes were equal or superior in their capacity to deconstruct lignocellulosic biomass. Mass spectrometry analysis revealed differential composition of catalytic and structural subunits (scaffoldins) in the different cellulosome samples. The most abundant catalytic subunits in all cellulosome types include Cel48S, Cel9K, Cel9Q, Cel9R, and Cel5G. Microcrystalline cellulose- and glucose-derived cellulosome samples showed higher endoglucanase-to-exoglucanase ratios and higher catalytic subunit-per-scaffoldin ratios compared to lignocellulose-derived cellulosome types. The results reported here highlight the finding that cellulosomes derived from cells grown on glucose and microcrystalline cellulose are more efficient in their action on cellulosic substrates than other cellulosome preparations. These results should be considered in the future development of C. thermocellum -based cellulolytic cocktails, designer cellulosomes, or engineering of improved strains for deconstruction of lignocellulosic biomass.

21 CFR 184.1372 - Insoluble glucose isomerase enzyme preparations.

Code of Federal Regulations, 2013 CFR

2013-04-01

... high fructose corn syrup described in § 184.1866. They are derived from recognized species of precisely... ingredient is used as an enzyme, as defined in § 170.3(o)(9) of this chapter, to convert glucose to fructose. (2) The ingredient is used in high fructose corn syrup, at levels not to exceed current good...

21 CFR 184.1372 - Insoluble glucose isomerase enzyme preparations.

Code of Federal Regulations, 2011 CFR

2011-04-01

... high fructose corn syrup described in § 184.1866. They are derived from recognized species of precisely... ingredient is used as an enzyme, as defined in § 170.3(o)(9) of this chapter, to convert glucose to fructose. (2) The ingredient is used in high fructose corn syrup, at levels not to exceed current good...

21 CFR 184.1372 - Insoluble glucose isomerase enzyme preparations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... high fructose corn syrup described in § 184.1866. They are derived from recognized species of precisely... ingredient is used as an enzyme, as defined in § 170.3(o)(9) of this chapter, to convert glucose to fructose. (2) The ingredient is used in high fructose corn syrup, at levels not to exceed current good...

21 CFR 184.1372 - Insoluble glucose isomerase enzyme preparations.

Code of Federal Regulations, 2012 CFR

2012-04-01

... high fructose corn syrup described in § 184.1866. They are derived from recognized species of precisely... ingredient is used as an enzyme, as defined in § 170.3(o)(9) of this chapter, to convert glucose to fructose. (2) The ingredient is used in high fructose corn syrup, at levels not to exceed current good...

Measurement of Enzyme Kinetics by Use of a Blood Glucometer: Hydrolysis of Sucrose and Lactose

ERIC Educational Resources Information Center

Heinzerling, Peter; Schrader, Frank; Schanze, Sascha

2012-01-01

An alternative analytical method for measuring the kinetic parameters of the enzymes invertase and lactase is described. Invertase hydrolyzes sucrose to glucose and fructose and lactase hydrolyzes lactose to glucose and galactose. In most enzyme kinetics studies, photometric methods or test strips are used to quantify the derivates of the…

Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B-cells

PubMed Central

Le, Anne; Lane, Andrew N.; Hamaker, Max; Bose, Sminu; Gouw, Arvin; Barbi, Joseph; Tsukamoto, Takashi; Rojas, Camilio J.; Slusher, Barbara S.; Zhang, Haixia; Zimmerman, Lisa J.; Liebler, Daniel C.; Slebos, Robbert J.C.; Lorkiewicz, Pawel K.; Higashi, Richard M.; Fan, Teresa W. M.; Dang, Chi V.

2012-01-01

Summary Because MYC plays a causal role in many human cancers, including those with hypoxic and nutrient-poor tumor microenvironments, we have determined the metabolic responses of a MYC-inducible human Burkitt lymphoma model P493 cell line to aerobic and hypoxic conditions, and to glucose deprivation, using Stable Isotope Resolved Metabolomics. Using [U-13C]-glucose as the tracer, both glucose consumption and lactate production were increased by MYC expression and hypoxia. Using [U-13C,15N]-glutamine as the tracer, glutamine import and metabolism through the TCA cycle persisted under hypoxia, and glutamine contributed significantly to citrate carbons. Under glucose deprivation, glutamine-derived fumarate, malate, and citrate were significantly increased. Their 13C labeling patterns demonstrate an alternative energy-generating glutaminolysis pathway involving a glucose-independent TCA cycle. The essential role of glutamine metabolism in cell survival and proliferation under hypoxia and glucose deficiency, makes them susceptible to the glutaminase inhibitor BPTES, and hence could be targeted for cancer therapy. PMID:22225880

A reagentless enzymatic fluorescent biosensor for glucose based on upconverting glasses, as excitation source, and chemically modified glucose oxidase.

PubMed

Del Barrio, Melisa; Cases, Rafael; Cebolla, Vicente; Hirsch, Thomas; de Marcos, Susana; Wilhelm, Stefan; Galbán, Javier

2016-11-01

Upon near-infrared excitation Tm(3+)+Yb(3+) doped fluorohafnate glasses present upconversion properties and emit visible light. This property permits to use these glasses (UCG) as excitation sources for fluorescent optical biosensors. Taking this into account, in this work a fluorescent biosensor for glucose determination is designed and evaluated. The biosensor combines the UCG and the fluorescence of the enzyme glucose oxidase chemically modified with a fluorescein derivative (GOx-FS), whose intensity is modified during the enzymatic reaction with glucose. Optical parameters have been optimized and a mathematical model describing the behavior of the analytical signal is suggested. Working in FIA mode, the biosensor responds to glucose concentrations up to, at least, 15mM with a limit of detection of 1.9mM. The biosensor has a minimum lifetime of 9 days and has been applied to glucose determination in drinks. The applicability of the sensor was tested by glucose determination in two fruit juices. Copyright © 2016 Elsevier B.V. All rights reserved.

Glucose-Specific Polymer Hydrogels—A Reassessment

PubMed Central

Fazal, Furqan M.; Hansen, David E.

2007-01-01

Polymer hydrogels synthesized by crosslinking poly(allylamine hydrochloride) with (±)-epichlorohydrin in the presence of D-glucose-6-phosphate monobarium salt do not show imprinting on the molecular level. A series of hydrogels were prepared using the following five templates: D-glucose-6-phosphate monobarium salt, D-glucose, L-glucose, barium hydrogen phosphate (BaHPO4), and D-gluconamide; a hydrogel was also prepared in the absence of a template. For all six hydrogels, batch binding studies were conducted with D-glucose, L-glucose, D-fructose and D-gluconamide. The extent of analyte sugar binding was determined using 1H-NMR. Each hydrogel shows approximately the same relative binding affinity for the different sugar derivatives, and none displays selectivity for either glucose enantiomer. The results of the binding studies correlate with the octanol-water partition coefficients of the sugars, indicative that differential solubilities in the bulk polymer account for the binding affinities observed. Thus, in contrast to templated hydrogels prepared using methacrylate- or acrylamide-based reagents, true imprinting does not occur in this novel, crosslinked-poly(allylamine hydrochloride) system. PMID:17035016

Glucose-specific poly(allylamine) hydrogels--a reassessment.

PubMed

Fazal, Furqan M; Hansen, David E

2007-01-01

Polymer hydrogels synthesized by crosslinking poly(allylamine hydrochloride) with (+/-)-epichlorohydrin in the presence of d-glucose-6-phosphate monobarium salt do not show imprinting on the molecular level. A series of hydrogels was prepared using the following five templates: d-glucose-6-phosphate monobarium salt, d-glucose, l-glucose, barium hydrogen phosphate (BaHPO(4)), and d-gluconamide; a hydrogel was also prepared in the absence of a template. For all six hydrogels, batch binding studies were conducted with d-glucose, l-glucose, d-fructose, and d-gluconamide. The extent of analyte sugar binding was determined using (1)H NMR. Each hydrogel shows approximately the same relative binding affinity for the different sugar derivatives, and none displays selectivity for either glucose enantiomer. The results of the binding studies correlate with the octanol-water partition coefficients of the sugars, indicative that differential solubilities in the bulk polymer account for the binding affinities observed. Thus, in contrast to templated hydrogels prepared using methacrylate- or acrylamide-based reagents, true imprinting does not occur in this novel, crosslinked-poly(allylamine hydrochloride) system.

Targeted Disruption of Pancreatic-Derived Factor (PANDER, FAM3B) Impairs Pancreatic β-Cell Function

PubMed Central

Robert-Cooperman, Claudia E.; Carnegie, Jason R.; Wilson, Camella G.; Yang, Jichun; Cook, Joshua R.; Wu, Jianmei; Young, Robert A.; Wolf, Bryan A.; Burkhardt, Brant R.

2010-01-01

OBJECTIVE Pancreatic-derived factor (PANDER, FAM3B) is a pancreatic islet-specific cytokine-like protein that is secreted from β-cells upon glucose stimulation. The biological function of PANDER is unknown, and to address this we generated and characterized a PANDER knockout mouse. RESEARCH DESIGN AND METHODS To generate the PANDER knockout mouse, the PANDER gene was disrupted and its expression was inhibited by homologous recombination via replacement of the first two exons, secretion signal peptide and transcriptional start site, with the neomycin gene. PANDER−/− mice were then phenotyped by a number of in vitro and in vivo tests to evaluate potential effects on glucose regulation, insulin sensitivity, and β-cell morphology and function. RESULTS Glucose tolerance tests demonstrated significantly higher blood glucose levels in PANDER−/− versus wild-type male mice. To identify the mechanism of the glucose intolerance, insulin sensitivity and pancreatic β-cell function were examined. Hyperinsulinemic-euglycemic clamps and insulin tolerance testing showed similar insulin sensitivity for both the PANDER−/− and wild-type mice. The in vivo insulin response following intraperitoneal glucose injection surprisingly produced significantly higher insulin levels in the PANDER−/− mice, whereas insulin release was blunted with arginine administration. Islet perifusion and calcium imaging studies showed abnormal responses of the PANDER−/− islets to glucose stimulation. In contrast, neither islet architecture nor insulin content was impacted by the loss of PANDER. Interestingly, the elevated insulin levels identified in vivo were attributed to decreased hepatic insulin clearance in the PANDER−/− islets. Taken together, these results demonstrated decreased pancreatic β-cell function in the PANDER−/− mouse. CONCLUSIONS These results support a potential role of PANDER in the pancreatic β-cell for regulation or facilitation of insulin secretion. PMID:20566664

Recent Developments of C-Aryl Glucoside SGLT2 Inhibitors.

PubMed

Zhang, Yang; Liu, Zhao-Peng

2016-01-01

Sodium-glucose cotransporter 2 (SGLT2) is almost exclusively expressed in the proximal renal tubules. It is responsible for about 90% of the glucose reabsorption from tubular fluid. Selective inhibition of SGLT2 is expected to favor in the normalization of plasma glucose levels in T2DM patients through the prevention of renal glucose reabsorption and the promotion of glucose excretion from urine. Selective SGLT2 inhibitors have the merits to minimize the gastrointestinal side effects associated with SGLT1 inhibition, and selective SGLT2 inhibition may have a low risk of hypoglycemia. Since the C-aryl glucosides are metabolically more stable than the O-glucosides, numerous efforts have been made in the development of potent and selective C-aryl glucoside SGLT2 inhibitors, and a number of them are now used as anti-diabetes drugs in clinic or at various stages of clinical developments. Based on their structural features, in this review, these SGLT2 inhibitors are classified as three types: the phenyl/arylmethylphenyl C-glucosides, with an emphasis on the modifications on the proximal and/or the distal phenyl ring, and the spacer; the heteroarylmethylphenyl Cglucosides, with a replacement of the distal phenyl ring by a heterocycle like pyridazine, pyrimidine, thiophene and benzothiophene, thiazole, 1,3,4-thiadiazole, and triazolopyridinone; and the glucose-modified Caryl glucosides, including the glucose C-1 derived O-spiroketals, C-4 gem-difluoro analogues, C-5 and C-6 modified derivatives, dioxa-bicyclo[3.2.1]octane bridged ketals, the thioglucosides, and carbasugars. The structure-activity relationships (SARs) of each type along with their inhibitory potency against human SGLT2 and selectivity over human SGLT1 are discussed.

In Silico Testing of an Artificial-Intelligence-Based Artificial Pancreas Designed for Use in the Intensive Care Unit Setting

PubMed Central

DeJournett, Leon; DeJournett, Jeremy

2016-01-01

Background: Effective glucose control in the intensive care unit (ICU) setting has the potential to decrease morbidity and mortality rates which should in turn lead to decreased health care expenditures. Current ICU-based glucose controllers are mathematically derived, and tend to be based on proportional integral derivative (PID) or model predictive control (MPC). Artificial intelligence (AI)–based closed loop glucose controllers may have the ability to achieve control that improves on the results achieved by either PID or MPC controllers. Method: We conducted an in silico analysis of an AI-based glucose controller designed for use in the ICU setting. This controller was tested using a mathematical model of the ICU patient’s glucose-insulin system. A total of 126 000 unique 5-day simulations were carried out, resulting in 107 million glucose values for analysis. Results: For the 7 control ranges tested, with a sensor error of ±10%, the following average results were achieved: (1) time in control range, 94.2%, (2) time in range 70-140 mg/dl, 97.8%, (3) time in hyperglycemic range (>140 mg/dl), 2.1%, and (4) time in hypoglycemic range (<70 mg/dl), 0.09%. In addition, the average coefficient of variation (CV) was 11.1%. Conclusions: This in silico study of an AI-based closed loop glucose controller shows that it may be able to improve on the results achieved by currently existing ICU-based PID/MPC controllers. If these results are confirmed in clinical testing, this AI-based controller could be used to create an artificial pancreas system for use in the ICU setting. PMID:27301982

The level of menadione redox-cycling in pancreatic β-cells is proportional to the glucose concentration: role of NADH and consequences for insulin secretion

PubMed Central

Heart, Emma; Palo, Meridith; Womack, Trayce; Smith, Peter J. S.; Gray, Joshua P.

2011-01-01

Pancreatic β-cells release insulin in response to elevation of glucose from basal (4-7 mM) to stimulatory (8-16 mM) levels. Metabolism of glucose by the β-cell results in the production of low levels of reactive oxygen intermediates (ROI), such as hydrogen peroxide (H2O2), a newly recognized coupling factor linking glucose metabolism to insulin secretion. However, high and toxic levels of H2O2 inhibit insulin secretion. Menadione, which produces H2O2 via redox cycling mechanism in a dose-dependent manner, was investigated for its effect on β-cell metabolism and insulin secretion in INS-1 832/13, a rat β-cell insulinoma cell line, and primary rodent islets. Menadione-dependent redox cycling and resulting H2O2 production under stimulatory glucose exceeded several-fold those reached at basal glucose. This was paralleled by a differential effect of menadione (0.1-10 μM) on insulin secretion, which was enhanced at basal, but inhibited at stimulatory glucose. Redox cycling of menadione and H2O2 formation was dependent on glycolytically-derived NADH, as inhibition of glycolysis and application of non-glycogenic insulin secretagogues did not support redox cycling. In addition, activity of plasma membrane electron transport, a system dependent in part on glycolytically-derived NADH, was also inhibited by menadione. Menadione-dependent redox cycling was sensitive to the NQO1 inhibitor dicoumarol and the flavoprotein inhibitor diphenylene iodonium, suggesting a role for NQO1 and other oxidoreductases in this process. These data may explain the apparent dichotomy between the stimulatory and inhibitory effects of H2O2 and menadione on insulin secretion. PMID:22115979

The level of menadione redox-cycling in pancreatic β-cells is proportional to the glucose concentration: role of NADH and consequences for insulin secretion.

PubMed

Heart, Emma; Palo, Meridith; Womack, Trayce; Smith, Peter J S; Gray, Joshua P

2012-01-15

Pancreatic β-cells release insulin in response to elevation of glucose from basal (4-7mM) to stimulatory (8-16mM) levels. Metabolism of glucose by the β-cell results in the production of low levels of reactive oxygen intermediates (ROI), such as hydrogen peroxide (H(2)O(2)), a newly recognized coupling factor linking glucose metabolism to insulin secretion. However, high and toxic levels of H(2)O(2) inhibit insulin secretion. Menadione, which produces H(2)O(2) via redox cycling mechanism in a dose-dependent manner, was investigated for its effect on β-cell metabolism and insulin secretion in INS-1 832/13, a rat β-cell insulinoma cell line, and primary rodent islets. Menadione-dependent redox cycling and resulting H(2)O(2) production under stimulatory glucose exceeded several-fold those reached at basal glucose. This was paralleled by a differential effect of menadione (0.1-10μM) on insulin secretion, which was enhanced at basal, but inhibited at stimulatory glucose. Redox cycling of menadione and H(2)O(2) formation was dependent on glycolytically-derived NADH, as inhibition of glycolysis and application of non-glycogenic insulin secretagogues did not support redox cycling. In addition, activity of plasma membrane electron transport, a system dependent in part on glycolytically-derived NADH, was also inhibited by menadione. Menadione-dependent redox cycling was sensitive to the NQO1 inhibitor dicoumarol and the flavoprotein inhibitor diphenylene iodonium, suggesting a role for NQO1 and other oxidoreductases in this process. These data may explain the apparent dichotomy between the stimulatory and inhibitory effects of H(2)O(2) and menadione on insulin secretion. Published by Elsevier Inc.

Role of various indices derived from an oral glucose tolerance test in the prediction of conversion from prediabetes to type 2 diabetes.

PubMed

Kim, Ye An; Ku, Eu Jeong; Khang, Ah Reum; Hong, Eun Shil; Kim, Kyoung Min; Moon, Jae Hoon; Choi, Sung Hee; Park, Kyong Soo; Jang, Hak Chul; Lim, Soo

2014-11-01

The clinical implications of prediabetes for development of type 2 diabetes may differ for Asian ethnicity. We investigated various indices derived from a 2-h oral glucose tolerance test (OGTT) in people with prediabetes to predict their future risk of diabetes. We recruited 406 consecutive subjects with prediabetes from 2005 to 2006 and followed them up every 3-6 months for up to 9 years. Prediabetes was defined as isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), combined glucose intolerance (CGI), or isolated elevated HbA1c (5.7-6.4%, 39-46 mmol/mol) without IFG or IGT. The rate of diabetes conversion was compared between prediabetes categories. The association of glycemic indices with development of diabetes was also investigated. Eighty-one patients were diagnosed with diabetes during the 9-year follow-up (median 46.0 months). The rate of diabetes conversion was higher in subjects with CGI (31.9%), or isolated IGT (18.5%) than in those with isolated IFG (15.2%) or isolated elevated HbA1c (10.9%). Surrogate markers reflecting β-cell dysfunction were more closely associated with diabetes conversion than insulin resistance indices. Subjects with a 30-min postload glucose ≥ 165 mg/dL and a 30-min C-peptide < 5 ng/mL had 8.83 times greater risk (95% confidence interval 2.98-26.16) of developing diabetes than other prediabetic subjects. In Asians, at least Koreans, β-cell dysfunction seems to be the major determinant for diabetes conversion. A combination of high glucose and low C-peptide levels at 30 min after OGTT may be a good predictor for diabetes conversion in this population. Copyright © 2014. Published by Elsevier Ireland Ltd.

High Liver Enzyme Concentrations are Associated with Higher Glycemia, but not with Glycemic Variability, in Individuals without Diabetes Mellitus.

PubMed

Noordam, Raymond; Vermond, Debbie; Drenth, Hermijntje; Wijman, Carolien A; Akintola, Abimbola A; van der Kroef, Sabrina; Jansen, Steffy W M; Huurman, Neline C; Schutte, Bianca A M; Beekman, Marian; Slagboom, P Eline; Mooijaart, Simon P; van Heemst, Diana

2017-01-01

Elevated concentrations of liver enzymes have been associated with an increased risk of developing type 2 diabetes mellitus. However, it remains unclear to which specific aspects of diurnal glucose metabolism these associate most. We aimed to investigate the associations between liver enzyme concentrations and 24 h-glucose trajectories in individuals without diabetes mellitus from three independent cohorts. This cross-sectional study included 436 participants without diabetes mellitus from the Active and Healthy Aging Study, the Switchbox Study, and the Growing Old Together Study. Fasting blood samples were drawn to measure gamma-glutamyltransferase (GGT), alanine transaminase, and aspartate transaminase. Measures of glycemia (e.g., nocturnal and diurnal mean glucose levels) and glycemic variability (e.g., mean amplitude of glucose excursions) were derived from continuous glucose monitoring. Analyses were performed separately for the three cohorts; derived estimates were additionally meta-analyzed. After meta-analyses of the three cohorts, elevated liver enzyme concentrations, and specifically elevated GGT concentrations, were associated with higher glycemia. More specific, participants in the highest GGT tertile (GGT ≥37.9 U/L) had a 0.39 mmol/L (95% confidence interval: 0.23, 0.56) higher mean nocturnal glucose (3:00 to 6:00 a.m.) and a 0.23 mmol/L (0.10, 0.36) higher diurnal glucose (6:00 to 0:00 a.m.) than participants in the lowest GGT tertile (GGT <21.23 U/L). However, elevated liver enzyme concentrations were not associated with a higher glycemic variability. Though elevated liver enzyme concentrations did not associate with higher glycemic variability in participants without diabetes mellitus, specifically, elevated GGT concentrations associated with higher glycemia.

In Silico Testing of an Artificial-Intelligence-Based Artificial Pancreas Designed for Use in the Intensive Care Unit Setting.

PubMed

DeJournett, Leon; DeJournett, Jeremy

2016-11-01

Effective glucose control in the intensive care unit (ICU) setting has the potential to decrease morbidity and mortality rates which should in turn lead to decreased health care expenditures. Current ICU-based glucose controllers are mathematically derived, and tend to be based on proportional integral derivative (PID) or model predictive control (MPC). Artificial intelligence (AI)-based closed loop glucose controllers may have the ability to achieve control that improves on the results achieved by either PID or MPC controllers. We conducted an in silico analysis of an AI-based glucose controller designed for use in the ICU setting. This controller was tested using a mathematical model of the ICU patient's glucose-insulin system. A total of 126 000 unique 5-day simulations were carried out, resulting in 107 million glucose values for analysis. For the 7 control ranges tested, with a sensor error of ±10%, the following average results were achieved: (1) time in control range, 94.2%, (2) time in range 70-140 mg/dl, 97.8%, (3) time in hyperglycemic range (>140 mg/dl), 2.1%, and (4) time in hypoglycemic range (<70 mg/dl), 0.09%. In addition, the average coefficient of variation (CV) was 11.1%. This in silico study of an AI-based closed loop glucose controller shows that it may be able to improve on the results achieved by currently existing ICU-based PID/MPC controllers. If these results are confirmed in clinical testing, this AI-based controller could be used to create an artificial pancreas system for use in the ICU setting. © 2016 Diabetes Technology Society.

Toward Homosuccinate Fermentation: Metabolic Engineering of Corynebacterium glutamicum for Anaerobic Production of Succinate from Glucose and Formate

PubMed Central

Litsanov, Boris; Brocker, Melanie

2012-01-01

Previous studies have demonstrated the capability of Corynebacterium glutamicum for anaerobic succinate production from glucose under nongrowing conditions. In this work, we have addressed two shortfalls of this process, the formation of significant amounts of by-products and the limitation of the yield by the redox balance. To eliminate acetate formation, a derivative of the type strain ATCC 13032 (strain BOL-1), which lacked all known pathways for acetate and lactate synthesis (Δcat Δpqo Δpta-ackA ΔldhA), was constructed. Chromosomal integration of the pyruvate carboxylase gene pycP458S into BOL-1 resulted in strain BOL-2, which catalyzed fast succinate production from glucose with a yield of 1 mol/mol and showed only little acetate formation. In order to provide additional reducing equivalents derived from the cosubstrate formate, the fdh gene from Mycobacterium vaccae, coding for an NAD+-coupled formate dehydrogenase (FDH), was chromosomally integrated into BOL-2, leading to strain BOL-3. In an anaerobic batch process with strain BOL-3, a 20% higher succinate yield from glucose was obtained in the presence of formate. A temporary metabolic blockage of strain BOL-3 was prevented by plasmid-borne overexpression of the glyceraldehyde 3-phosphate dehydrogenase gene gapA. In an anaerobic fed-batch process with glucose and formate, strain BOL-3/pAN6-gap accumulated 1,134 mM succinate in 53 h with an average succinate production rate of 1.59 mmol per g cells (dry weight) (cdw) per h. The succinate yield of 1.67 mol/mol glucose is one of the highest currently described for anaerobic succinate producers and was accompanied by a very low level of by-products (0.10 mol/mol glucose). PMID:22389371

Blood glucose level reconstruction as a function of transcapillary glucose transport.

PubMed

Koutny, Tomas

2014-10-01

A diabetic patient occasionally undergoes a detailed monitoring of their glucose levels. Over the course of a few days, a monitoring system provides a detailed track of their interstitial fluid glucose levels measured in their subcutaneous tissue. A discrepancy in the blood and interstitial fluid glucose levels is unimportant because the blood glucose levels are not measured continuously. Approximately five blood glucose level samples are taken per day, and the interstitial fluid glucose level is usually measured every 5min. An increased frequency of blood glucose level sampling would cause discomfort for the patient; thus, there is a need for methods to estimate blood glucose levels from the glucose levels measured in subcutaneous tissue. The Steil-Rebrin model is widely used to describe the relationship between blood and interstitial fluid glucose dynamics. However, we measured glucose level patterns for which the Steil-Rebrin model does not hold. Therefore, we based our research on a different model that relates present blood and interstitial fluid glucose levels to future interstitial fluid glucose levels. Using this model, we derived an improved model for calculating blood glucose levels. In the experiments conducted, this model outperformed the Steil-Rebrin model while introducing no additional requirements for glucose sample collection. In subcutaneous tissue, 26.71% of the calculated blood glucose levels had absolute values of relative differences from smoothed measured blood glucose levels less than or equal to 5% using the Steil-Rebrin model. However, the same difference interval was encountered in 63.01% of the calculated blood glucose levels using the proposed model. In addition, 79.45% of the levels calculated with the Steil-Rebrin model compared with 95.21% of the levels calculated with the proposed model had 20% difference intervals. Copyright © 2014 Elsevier Ltd. All rights reserved.

[13C]Glucose Breath Testing Provides a Noninvasive Measure of Insulin Resistance: Calibration Analyses Against Clamp Studies

PubMed Central

Hussain, Maysa; Jangorbhani, Morteza; Schuette, Sally; Considine, Robert V.; Chisholm, Robin L.

2014-01-01

Abstract Background: Exhaled 13CO2 following ingestion of [13C]glucose with a standard oral glucose tolerance load correlates with blood glucose values but is determined by tissue glucose uptake. Therefore exhaled 13CO2 may also be a surrogate measure of the whole-body glucose disposal rate (GDR) measured by the gold standard hyperinsulinemic euglycemic clamp. Subjects and Methods: Subjects from across the glycemia range were studied on 2 consecutive days under fasting conditions. On Day 1, a 75-g oral glucose load spiked with [13C]glucose was administered. On Day 2, a hyperinsulinemic euglycemic clamp was performed. Correlations between breath parameters and clamp-derived GDR were evaluated, and calibration analyses were performed to evaluate the precision of breath parameter predictions of clamp measures. Results: Correlations of breath parameters with GDR and GDR per kilogram of fat-free mass (GDRffm) ranged from 0.54 to 0.61 and 0.54 to 0.66, respectively (all P<0.001). In calibration analyses the root mean square error for breath parameters predicting GDR and GDRffm ranged from 2.32 to 2.46 and from 3.23 to 3.51, respectively. Cross-validation prediction error (CVPE) estimates were 2.35–2.51 (GDR) and 3.29–3.57 (GDRffm). Prediction precision of breath enrichment at 180 min predicting GDR (CVPE=2.35) was superior to that for inverse insulin (2.68) and the Matsuda Index (2.51) but inferior to that for the log of homeostasis model assessment (2.21) and Quantitative Insulin Sensitivity Check Index (2.29) (all P<10−5). Similar patterns were seen for predictions of GDRffm. Conclusions: 13CO2 appearance in exhaled breath following a standard oral glucose load with added [13C]glucose provides a valid surrogate index of clamp-derived measures of whole-body insulin resistance, with good accuracy and precision. This noninvasive breath test-based approach can provide a useful measure of whole-body insulin resistance in physiologic and epidemiologic studies. PMID:24116833

Bioconversion of lignocellulose-derived sugars to ethanol by engineered Saccharomyces cerevisiae.

PubMed

Madhavan, Anjali; Srivastava, Aradhana; Kondo, Akihiko; Bisaria, Virendra S

2012-03-01

Lignocellulosic biomass from agricultural and agro-industrial residues represents one of the most important renewable resources that can be utilized for the biological production of ethanol. The yeast Saccharomyces cerevisiae is widely used for the commercial production of bioethanol from sucrose or starch-derived glucose. While glucose and other hexose sugars like galactose and mannose can be fermented to ethanol by S. cerevisiae, the major pentose sugars D-xylose and L-arabinose remain unutilized. Nevertheless, D-xylulose, the keto isomer of xylose, can be fermented slowly by the yeast and thus, the incorporation of functional routes for the conversion of xylose and arabinose to xylulose or xylulose-5-phosphate in Saccharomyces cerevisiae can help to improve the ethanol productivity and make the fermentation process more cost-effective. Other crucial bottlenecks in pentose fermentation include low activity of the pentose phosphate pathway enzymes and competitive inhibition of xylose and arabinose transport into the cell cytoplasm by glucose and other hexose sugars. Along with a brief introduction of the pretreatment of lignocellulose and detoxification of the hydrolysate, this review provides an updated overview of (a) the key steps involved in the uptake and metabolism of the hexose sugars: glucose, galactose, and mannose, together with the pentose sugars: xylose and arabinose, (b) various factors that play a major role in the efficient fermentation of pentose sugars along with hexose sugars, and (c) the approaches used to overcome the metabolic constraints in the production of bioethanol from lignocellulose-derived sugars by developing recombinant S. cerevisiae strains.

Treatment of Metastatic Lymph Nodes in the Neck from Papillary Thyroid Carcinoma with Percutaneous Laser Ablation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mauri, Giovanni, E-mail: vanni.mauri@gmail.com; Cova, Luca; Ierace, Tiziana

2016-07-15

PurposeTo assess the effectiveness of percutaneous laser ablation (PLA) of cervical lymph node metastases from papillary thyroid carcinoma.Materials and Methods24 patients (62.3 ± 13.2 year; range 32–80) previously treated with thyroidectomy, neck dissection, and radioiodine ablation underwent ultrasound-guided PLA of 46 {sup 18}FDG-PET/CT—positive metachronous nodal metastases. All patients were at high surgical risk or refused surgery and were unsuitable for additional radioiodine ablation. A 300 µm quartz fiber and a continuous-wave Nd-YAG laser operating at 1.064 mm were used. Technical success, rate of complications, rate of serological conversion, and local control at follow-up were derived. Fisher’s exact test and Mann–Whitney U test were used andmore » Kaplan–Meier curve calculated.ResultsTechnical success was obtained in all 46 lymph nodes (100 %). There were no major complications. Thyroglobulin levels decreased from 8.40 ± 9.25 ng/ml before treatment to 2.73 ± 4.0 ng/ml after treatment (p = 0.011), with serological conversion in 11/24 (45.8 %) patients. Overall, local control was obtained in 40/46 (86.9 %) lymph nodes over 30 ± 11 month follow-up, with no residual disease seen at imaging in 19/24 (79.1 %) patients. Local control was achieved in 40/46 (86.9 %) lymph nodes at 1 year and in all of the 25 nodes (100 %) followed for 3 years. Estimated mean time to progression was 38.6 ± 2.7 m.ConclusionUltrasound-guided PLA is a feasible, safe, and effective therapy for the treatment of cervical lymph node metastases from papillary thyroid carcinoma.« less

Glucose-derived AGEs enhance human gastric cancer metastasis through RAGE/ERK/Sp1/MMP2 cascade.

PubMed

Deng, Ruyuan; Mo, Fengbo; Chang, Bowen; Zhang, Qi; Ran, Hui; Yang, Shuhua; Zhu, Zhiqiang; Hu, Lei; Su, Qing

2017-11-28

Advanced glycation end products (AGEs) have been reported to take part in many cancer processes. Whether AGEs contribute to gastric cancer (GC) course and the underlying mechanism are still unclear. Here, glucose-derived AGEs are detected to be accumulated in tumor tissues and blood of patients with GC. As the receptor for AGEs, RAGE is highly expressed in cancer tissues, and closely associated with the depth of cancer invasion, lymph node metastasis and TNM stage. Both in vivo and in vitro treatment of AGEs accelerate the tumor invasion and metastasis, with upregualtion of RAGE, Specificity Protein 1 (Sp1), and MMP2 protein expression, as well as enhancement of MMP2 activity. Either RAGE-blocking antibody or Sp1-knockdown can partially block the AGEs-induced effects. Moreover, AGEs increased the phosphorylation of ERK, and reducing the phosphorylation level of ERK by MEK1/2 inhibitor decreased the expression of Sp1. These results indicate that accumulation of glucose-derived AGEs may act as one of potential risk factors for GC progression and promote the invasion and metastasis of gastric cancer partially through the activation of RAGE/ERK/Sp1/MMP2 pathway.

Glucose-derived AGEs enhance human gastric cancer metastasis through RAGE/ERK/Sp1/MMP2 cascade

PubMed Central

Deng, Ruyuan; Mo, Fengbo; Chang, Bowen; Zhang, Qi; Ran, Hui; Yang, Shuhua; Zhu, Zhiqiang; Hu, Lei; Su, Qing

2017-01-01

Advanced glycation end products (AGEs) have been reported to take part in many cancer processes. Whether AGEs contribute to gastric cancer (GC) course and the underlying mechanism are still unclear. Here, glucose-derived AGEs are detected to be accumulated in tumor tissues and blood of patients with GC. As the receptor for AGEs, RAGE is highly expressed in cancer tissues, and closely associated with the depth of cancer invasion, lymph node metastasis and TNM stage. Both in vivo and in vitro treatment of AGEs accelerate the tumor invasion and metastasis, with upregualtion of RAGE, Specificity Protein 1 (Sp1), and MMP2 protein expression, as well as enhancement of MMP2 activity. Either RAGE-blocking antibody or Sp1-knockdown can partially block the AGEs-induced effects. Moreover, AGEs increased the phosphorylation of ERK, and reducing the phosphorylation level of ERK by MEK1/2 inhibitor decreased the expression of Sp1. These results indicate that accumulation of glucose-derived AGEs may act as one of potential risk factors for GC progression and promote the invasion and metastasis of gastric cancer partially through the activation of RAGE/ERK/Sp1/MMP2 pathway. PMID:29262634

Glucose and pyruvate metabolism in preimplantation blastocysts from normal and diabetic rats.

PubMed

Dufrasnes, E; Vanderheyden, I; Robin, D; Delcourt, J; Pampfer, S; De Hertogh, R

1993-05-01

Glucose metabolism was analysed in day-5 rat blastocysts incubated in the presence of [5-3H]-, [6-14C]- or [U-14C]glucose. Glycolysis, quantified by 3H2O recovery rate, was the main pathway of glucose utilization by fresh (11.5 +/- 0.36 pmol per embryo h-1) or cultured (24 h) blastocysts (20.4 +/- 0.6 pmol per embryo h-1). Glucose consumption rate was almost saturated at a medium glucose concentration of 0.28 mmol l-1 (Km: 0.17 mmol l-1; Vmax: 23 pmol per embryo h-1). A further 10% increase in glucose utilization was obtained with a tenfold higher glucose concentration (3 mmol l-1). Phloretin completely abolished the rapid component of glucose utilization kinetics, suggesting the existence of a Na(+)-independent glucose transport system. Less than 1% of [6-14C]glucose consumed by cultured blastocysts was oxidized through the Krebs cycle. [1-14C]pyruvate, however, was oxidized at a rate of 2 pmol per embryo h-1 by fresh blastocysts. The pentose-phosphate pathway accounted for about 2% of glucose utilization. One to two per cent of the total glucose metabolized in 24 h was retained in macromolecules. Insulin had no effect on glucose uptake, utilization, incorporation and turnover, or on pyruvate oxidation. Blastocysts from diabetic mothers utilized glucose at a rate similar to that of normal blastocysts. These results show that glucose is actively taken up by rat blastocysts and utilized mainly through the Embden-Meyerhof pathway, which is rapidly saturated at low glucose concentrations. Retention of glucose-derived products in macromolecules, although relatively small, may modulate the effect of high glucose concentrations on embryo growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Sex Differences in Maturation of Human Embryonic Stem Cell-Derived β Cells in Mice.

PubMed

Saber, Nelly; Bruin, Jennifer E; O'Dwyer, Shannon; Schuster, Hellen; Rezania, Alireza; Kieffer, Timothy J

2018-04-01

Pancreatic progenitors derived from human embryonic stem cells (hESCs) are now in clinical trials for insulin replacement in patients with type 1 diabetes. Animal studies indicate that pancreatic progenitor cells can mature into a mixed population of endocrine cells, including glucose-responsive β cells several months after implantion. However, it remains unclear how conditions in the recipient may influence the maturation and ultimately the function of these hESC-derived cells. Here, we investigated the effects of (1) pregnancy on the maturation of human stage 4 (S4) pancreatic progenitor cells and (2) the impact of host sex on both S4 cells and more mature stage 7 (S7) pancreatic endocrine cells implanted under the kidney capsule of immunodeficient SCID-beige mice. Pregnancy led to increased proliferation of endogenous pancreatic β cells, but did not appear to affect proliferation or maturation of S4 cells at midgestation. Interestingly, S4 and S7 cells both acquired glucose-stimulated C-peptide secretion in females before males. Moreover, S4 cells lowered fasting blood glucose levels in females sooner than in males, whereas the responses with S7 cells were similar. These data indicate that the host sex may impact the maturation of hESC-derived cells in vivo and that this effect can be minimized by more advanced differentiation of the cells before implantation.

Insulin sensitivity and beta-cell function in healthy cats: assessment with the use of the hyperglycemic glucose clamp.

PubMed

Slingerland, L I; Robben, J H; van Haeften, T W; Kooistra, H S; Rijnberk, A

2007-05-01

A hyperglycemic clamp (HGC) was developed for use in conscious cats. In 21 healthy, normal glucose tolerant cats glucose disposal rate (M), insulin sensitivity (ISI (HGC)), and beta-cell response (I) at arterial plasma glucose of 9 mmol.l (-1) were measured. The HGC was tolerated well and steady state glucose infusion was achieved. Compared to values reported for humans, M values for the cats were low, which appeared to relate to both a low ISI (HGC) and a low I. HGC measures correlated with fasting plasma glucose and insulin concentrations as well as with their HOMA (homeostasis model assessment) and QUICKI (quantitative insulin sensitivity check index) counterparts. Also, I and ISI (HGC) correlated with their counterparts derived from intravenous glucose tolerance tests. In conclusion, this is the first report of hyperglycemic glucose clamping in cats. The procedure (HGC) allows for measurements of glucose disposal, beta-cell response and insulin sensitivity. Compared to human data, both insulin sensitivity and insulin secretion appeared to be low in cats. This is compatible with the carnivorous nature of this species, for which insulin resistance would be advantageous during periods of restricted food availability.

Triglyceride, nonesterified fatty acids, and prediabetic neuropathy: role for oxidative-nitrosative stress.

PubMed

Lupachyk, Sergey; Watcho, Pierre; Hasanova, Nailia; Julius, Ulrich; Obrosova, Irina G

2012-04-15

Peripheral neuropathy develops in human subjects with prediabetes and metabolic syndrome before overt hyperglycemia. The contributions of impaired glucose tolerance and insulin signaling, hypertriglyceridemia and/or increased nonesterified fatty acids (NEFA), and hypercholesterolemia to this condition remain unknown. Niacin and its derivatives alleviate dyslipidemia with a minor effect on glucose homeostasis. This study evaluated the roles of impaired glucose tolerance versus dyslipidemia in prediabetic neuropathy using Zucker fatty (fa/fa) rats and the niacin derivative acipimox, as well as the interplay of hypertriglyceridemia, increased NEFA, and oxidative-nitrosative stress. Sixteen-week-old Zucker fatty rats with impaired glucose tolerance, obesity, hyperinsulinemia, hypertriglyceridemia, hypercholesterolemia, and increased NEFA displayed sensory nerve conduction velocity deficit, thermal and mechanical hypoalgesia, and tactile allodynia. Acipimox (100 mg kg(-1) day(-1), 4 weeks) reduced serum insulin, NEFA, and triglyceride concentrations without affecting glucose tolerance and hypercholesterolemia. It alleviated sensory nerve conduction velocity deficit and changes in behavioral measures of sensory function and corrected oxidative-nitrosative stress, but not impaired insulin signaling, in peripheral nerve. Elevated NEFA increased total and mitochondrial superoxide production and NAD(P)H oxidase activity in cultured human Schwann cells. In conclusion, hypertriglyceridemia and/or increased NEFA concentrations cause prediabetic neuropathy through oxidative-nitrosative stress. Lipid-lowering agents and antioxidants may find a use in the management of this condition. Copyright © 2012 Elsevier Inc. All rights reserved.

The association between brain-derived neurotrophic factor and central pulse pressure after an oral glucose tolerance test.

PubMed

Lee, I-Te; Chen, Chen-Huan; Wang, Jun-Sing; Fu, Chia-Po; Lee, Wen-Jane; Liang, Kae-Woei; Lin, Shih-Yi; Sheu, Wayne Huey-Herng

2018-01-01

Arterial stiffening blunts postprandial vasodilatation. We hypothesized that brain-derived neurotrophic factor (BDNF) may modulate postprandial central pulse pressure, a surrogate marker for arterial stiffening. A total of 82 non-diabetic subjects received a 75-g oral glucose tolerance test (OGTT) after overnight fasting. Serum BDNF concentrations were determined at 0, 30, and 120min to calculate the area under the curve (AUC). Brachial and central blood pressures were measured using a noninvasive central blood pressure monitor before blood withdrawals at 0 and 120min. With the median AUC of BDNF of 45(ng/ml)∗h as the cutoff value, the central pulse pressure after glucose intake was significantly higher in the subjects with a low BDNF than in those with a high BDNF (63±16 vs. 53±11mmHg, P=0.003), while the brachial pulse pressure was not significantly different between the 2 groups (P=0.099). In a multivariate linear regression model, a lower AUC of BDNF was an independent predictor of a higher central pulse pressure after oral glucose intake (linear regression coefficient-0.202, 95% confidence interval-0.340 to -0.065, P=0.004). After oral glucose challenge, a lower serum BDNF response is significantly associated with a higher central pulse pressure. Copyright © 2017 Elsevier B.V. All rights reserved.

Basal plasma insulin and homeostasis model assessment (HOMA) are indicators of insulin sensitivity in cats.

PubMed

Appleton, D J; Rand, J S; Sunvold, G D

2005-06-01

The objective of this study was to compare simpler indices of insulin sensitivity with the minimal model-derived insulin sensitivity index to identify a simple and reliable alternative method for assessing insulin sensitivity in cats. In addition, we aimed to determine whether this simpler measure or measures showed consistency of association across differing body weights and glucose tolerance levels. Data from glucose tolerance and insulin sensitivity tests performed in 32 cats with varying body weights (underweight to obese), including seven cats with impaired glucose tolerance, were used to assess the relationship between Bergman's minimal model-derived insulin sensitivity index (S(I)), and various simpler measures of insulin sensitivity. The most useful overall predictors of insulin sensitivity were basal plasma insulin concentrations and the homeostasis model assessment (HOMA), which is the product of basal glucose and insulin concentrations divided by 22.5. It is concluded that measurement of plasma insulin concentrations in cats with food withheld for 24 h, in conjunction with HOMA, could be used in clinical research projects and by practicing veterinarians to screen for reduced insulin sensitivity in cats. Such cats may be at increased risk of developing impaired glucose tolerance and type 2 diabetes mellitus. Early detection of these cats would enable preventative intervention programs such as weight reduction, increased physical activity and dietary modifications to be instigated.

A meta-analysis of efficacy of Morus alba Linn. to improve blood glucose and lipid profile.

PubMed

Phimarn, Wiraphol; Wichaiyo, Kittisak; Silpsavikul, Khuntawan; Sungthong, Bunleu; Saramunee, Kritsanee

2017-06-01

The previous studies have reported the Morus alba may improve blood glucose and lipid profile. The evidence from these studies is not consistent. This meta-analysis was to evaluate efficacy of products derived from M. alba on blood glucose and lipid levels. Literature was reviewed via international database (PubMed, PubMed Central, ScienceDirect, and SciSearch) and Thai databases. Thirteen RCTs with high quality, assessed by Jadad score, were included. M. alba expressed a significant reduction in postprandial glucose (PPG) at 30 min (MD -1.04, 95 % CI -1.36, -0.73), 60 min (MD -0.87, 95 % CI -1.27, -0.48) and 90 min (MD -0.55, 95 % CI -0.87, -0.22). The difference was not found in the levels of other glycaemic (FBS, HbA1C, or HOMA-IR) and lipidaemic (TC, TG, LDL, or HDL) markers. Serious adverse effects were found neither in the control nor in the group received M. alba. Products derived from M. alba can effectively contribute to the reduction in PPG levels, but large-scale RCTs would be informative.

Changes in the metabolic elimination profile of testosterone following exposure of the crustacean Daphnia magna to tributyltin.

PubMed

LeBlanc, G A; McLachlan, J B

2000-03-01

The biocide tributyltin has been found to cause the development of pseudohermaphroditic conditions in some neogastropod species. These abnormalities of the reproductive system have adversely affected the fecundity of some field populations of gastropods, resulting in local population declines. Current evidence suggests that tributyltin elicits these effects by interfering with the biotransformation of testosterone to other steroid derivatives, resulting in an elevation in endogenous testosterone or some of its bioactive derivatives. The purpose of the present study was to determine whether tributyltin altered testosterone metabolism in daphnids (Daphnia magna), a species commonly used in ecotoxicology testing. Exposure of daphnids to 1.2 microg (tin)/L caused a general increase in the rate of elimination of oxido-reduced, hydroxylated, and glucose-conjugated derivatives of testosterone. However, tributyltin exposure had no significant effect on the rate of elimination of the glucose-conjugated forms of the various oxido-reduced and hydroxylated derivatives of testosterone. As a result, the percentage of the oxido-reduced and hydroxylated metabolites of testosterone eliminated as glucose conjugates decreased with increasing tributyltin exposure levels. These results demonstrate that tributyltin causes alterations in testosterone metabolism in daphnids that would result in an increase in the production of oxido-reduced derivatives. These products are preferentially retained in the tissues of daphnids and are variously androgenic in vertebrates. The increased production of oxido-reduced derivatives of testosterone may be mechanically responsible for the masculinizing effects of tributyltin in some species and suggests that daphnids may be a suitable surrogate for evaluating the potential of chemicals to elicit this form of toxicity. Copyright 2000 Academic Press.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heart, Emma; Palo, Meridith; Womack, Trayce

Pancreatic β-cells release insulin in response to elevation of glucose from basal (4–7 mM) to stimulatory (8–16 mM) levels. Metabolism of glucose by the β-cell results in the production of low levels of reactive oxygen intermediates (ROI), such as hydrogen peroxide (H{sub 2}O{sub 2}), a newly recognized coupling factor linking glucose metabolism to insulin secretion. However, high and toxic levels of H{sub 2}O{sub 2} inhibit insulin secretion. Menadione, which produces H{sub 2}O{sub 2} via redox cycling mechanism in a dose-dependent manner, was investigated for its effect on β-cell metabolism and insulin secretion in INS-1 832/13, a rat β-cell insulinoma cellmore » line, and primary rodent islets. Menadione-dependent redox cycling and resulting H{sub 2}O{sub 2} production under stimulatory glucose exceeded several-fold those reached at basal glucose. This was paralleled by a differential effect of menadione (0.1–10 μM) on insulin secretion, which was enhanced at basal, but inhibited at stimulatory glucose. Redox cycling of menadione and H{sub 2}O{sub 2} formation was dependent on glycolytically-derived NADH, as inhibition of glycolysis and application of non-glycogenic insulin secretagogues did not support redox cycling. In addition, activity of plasma membrane electron transport, a system dependent in part on glycolytically-derived NADH, was also inhibited by menadione. Menadione-dependent redox cycling was sensitive to the NQO1 inhibitor dicoumarol and the flavoprotein inhibitor diphenylene iodonium, suggesting a role for NQO1 and other oxidoreductases in this process. These data may explain the apparent dichotomy between the stimulatory and inhibitory effects of H{sub 2}O{sub 2} and menadione on insulin secretion. -- Highlights: ► Menadione stimulation or inhibition of insulin secretion is dependent upon applied glucose levels. ► Menadione-dependent H{sub 2}O{sub 2} production is proportional to applied glucose levels. ► Quinone-mediated redox cycling is dependent on glycolysis.« less

Association of obesity risk SNPs in PCSK1 with insulin sensitivity and proinsulin conversion.

PubMed

Heni, Martin; Haupt, Axel; Schäfer, Silke A; Ketterer, Caroline; Thamer, Claus; Machicao, Fausto; Stefan, Norbert; Staiger, Harald; Häring, Hans-Ulrich; Fritsche, Andreas

2010-06-09

Prohormone convertase 1 is involved in maturation of peptides. Rare mutations in gene PCSK1, encoding this enzyme, cause childhood obesity and abnormal glucose homeostasis with elevated proinsulin concentrations. Common single nucleotide polymorphisms (SNPs) within this gene, rs6232 and rs6235, are associated with obesity. We studied whether these SNPs influence the prediabetic traits insulin resistance, beta-cell dysfunction, or glucose intolerance. We genotyped 1498 German subjects for SNPs rs6232 and rs6235 within PCSK1. The subjects were metabolically characterized by oral glucose tolerance test with glucose, insulin, proinsulin, and C-peptide measurements. A subgroup of 512 subjects underwent a hyperinsulinemic-euglycemic clamp. The minor allele frequencies were 25.8% for SNP rs6235 and 6.0% for rs6232. After adjustment for sex and age, we found no association of SNPs rs6235 and rs6232 with BMI or other weight-related traits (all p >or= 0.07). Both minor alleles, adjusted for sex, age, BMI and insulin sensitivity were associated with elevated AUCproinsulin and AUCproinsulin/AUCinsulin (rs6235: p(additive) model or= 0.08). The minor allele of SNP rs6232 was additionally associated with 15% higher OGTT-derived and 19% higher clamp-derived insulin sensitivity (pdom

Association of obesity risk SNPs in PCSK1 with insulin sensitivity and proinsulin conversion

PubMed Central

2010-01-01

Background Prohormone convertase 1 is involved in maturation of peptides. Rare mutations in gene PCSK1, encoding this enzyme, cause childhood obesity and abnormal glucose homeostasis with elevated proinsulin concentrations. Common single nucleotide polymorphisms (SNPs) within this gene, rs6232 and rs6235, are associated with obesity. We studied whether these SNPs influence the prediabetic traits insulin resistance, β-cell dysfunction, or glucose intolerance. Methods We genotyped 1498 German subjects for SNPs rs6232 and rs6235 within PCSK1. The subjects were metabolically characterized by oral glucose tolerance test with glucose, insulin, proinsulin, and C-peptide measurements. A subgroup of 512 subjects underwent a hyperinsulinemic-euglycemic clamp. Results The minor allele frequencies were 25.8% for SNP rs6235 and 6.0% for rs6232. After adjustment for sex and age, we found no association of SNPs rs6235 and rs6232 with BMI or other weight-related traits (all p ≥ 0.07). Both minor alleles, adjusted for sex, age, BMI and insulin sensitivity were associated with elevated AUCproinsulin and AUCproinsulin/AUCinsulin (rs6235: padditive model ≤ 0.009, effect sizes 8/8%, rs6232: pdominant model ≤ 0.01, effect sizes 10/21%). Insulin secretion was not affected by the variants (different secretion parameters, all p ≥ 0.08). The minor allele of SNP rs6232 was additionally associated with 15% higher OGTT-derived and 19% higher clamp-derived insulin sensitivity (pdom ≤ 0.0047), 4.5% lower HOMAIR (pdom = 0.02) and 3.5% lower 120-min glucose (pdom = 0.0003) independently of BMI and proinsulin conversion. SNP rs6235 was not associated with parameters of glucose metabolism. Conclusions Like rare mutations in PCSK1, the more common variants tested determine glucose-stimulated proinsulin conversion, but not insulin secretion. In addition, rs6232, encoding the amino acid exchange N221D, influences insulin sensitivity and glucose homeostasis. PMID:20534142

Regulation of ATP-binding Cassette Transporters and Cholesterol Efflux by Glucose in Primary Human Monocytes and Murine Bone Marrow-derived Macrophages

PubMed Central

Spartano, N. L.; Lamon-Fava, S.; Matthan, N. R.; Ronxhi, J.; Greenberg, A. S.; Obin, M. S.; Lichtenstein, A. H.

2014-01-01

Purpose Individuals with type 2 diabetes mellitus are at increased risk of developing atherosclerosis. This may be partially attributable to suppression of macrophage ATP-binding cassette (ABC) transporter mediated cholesterol efflux by sustained elevated blood glucose concentrations. 2 models were used to assess this potential relationship: human monocytes/leukocytes and murine bone marrow-derived macrophages (BMDM). Methods 10 subjects (4 F/6 M, 50–85 years, BMI 25–35 kg/m2) underwent an oral glucose challenge. Baseline and 1- and 2-h post-challenge ABC-transporter mRNA expression was determined in monocytes, leukocytes and peripheral blood mononuclear cells (PBMC). In a separate study, murine-BMDM were exposed to 5 mmol/L D-glucose (control) or additional 20 mmol/L D-or L-glucose and 25 ug/mL oxidized low density lipoprotein (oxLDL). High density lipoprotein (HDL)-mediated cholesterol efflux and ABC-transporter (ABCA1 and ABCG1) expression were determined. Results Baseline ABCA1and ABCG1 expression was lower (> 50 %) in human monocytes and PBMC than leukocytes (p < 0.05). 1 h post-challenge leukocyte ABCA1 and ABCG1 expression increased by 37 % and 30 %, respectively (p < 0.05), and began to return to baseline thereafter. There was no significant change in monocyte ABC-transporter expression. In murine BMDM, higher glucose concentrations suppressed HDL-mediated cholesterol efflux (10 %; p < 0.01) without significantly affecting ABCA1 and ABCG1 expression. Data demonstrate that leukocytes are not a reliable indicator of monocyte ABC-transporter expression. Conclusions Human monocyte ABC-transporter gene expression was unresponsive to a glucose challenge. Correspondingly, in BMDM, hyperglycemia attenuated macrophage cholesterol efflux in the absence of altered ABC-transporter expression, suggesting that hyperglycemia, per se, suppresses cholesterol transporter activity. This glucose-related impairment in cholesterol efflux may potentially contribute to diabetes-associated atherosclerosis. PMID:24838154

High glucose derived endothelial microparticles increase active caspase-3 and reduce microRNA-Let-7a expression in endothelial cells.

PubMed

Bammert, Tyler D; Hijmans, Jamie G; Reiakvam, Whitney R; Levy, Ma'ayan V; Brewster, Lillian M; Goldthwaite, Zoe A; Greiner, Jared J; Stockelman, Kelly A; DeSouza, Christopher A

2017-11-18

The experimental aim of this study was to determine the effects of high glucose-induced endothelial microparticles (EMPs) on endothelial cell susceptibility to apoptosis. Human umbilical vein endothelial cells (HUVECs) were cultured (3rd passage) and plated in 6-well plates at a density of 5.0 × 10 5  cells/condition. Cells were incubated with media containing 25 mM d-glucose (concentration representing a diabetic glycemic state) or 5 mM d-glucose (normoglycemic condition) for 48 h to generate EMPs. EMP identification (CD144 + expression) and concentration was determined by flow cytometry. HUVECs (3 × 10 6  cells/condition) were treated with EMPs generated from either the normal or high glucose conditions for 24 h. Intracellular concentration of active caspase-3 was determined by enzyme immunoassay. Cellular expression of miR-Let7a, an anti-apoptotic microRNA, was determined by RT-PCR using the ΔΔCT normalized to RNU6. High glucose-derived EMPs significantly increased both basal (1.5 ± 0.1 vs 1.0 ± 0.1 ng/mL) and staurosporine-stimulated (2.2 ± 0.2 vs 1.4 ± 0.1 ng/mL) active caspase-3 compared with normal glucose EMPs. Additionally, the expression of miR-Let-7a was markedly reduced (∼140%) by high glucose EMPs (0.43 ± 0.17 fold vs control). These results demonstrate that hyperglycemic-induced EMPs increase endothelial cell active caspase-3. This apoptotic effect may be mediated, at least in part, by a reduction in miR-Let-7a expression. Copyright © 2017 Elsevier Inc. All rights reserved.

Fetal radiation dose estimates for I-131 sodium iodide in cases where conception occurs after administration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sparks, R.B.; Stabin, M.G.

1999-01-01

After administration of I-131 to the female patient, the possibility of radiation exposure of the embryo/fetus exists if the patient becomes pregnant while radioiodine remains in the body. Fetal radiation dose estimates for such cases were calculated. Doses were calculated for various maternal thyroid uptakes and time intervals between administration and conception, including euthyroid and hyperthyroid cases. The maximum fetal dose calculating was about 9.8E-03 mGy/MBq, which occurred with 100% maternal thyroid uptake and a 1 week interval between administration and conception. Placental crossover of the small amount of radioiodine remaining 90 days after conception was also considered. Such crossovermore » could result in an additional fetal dose of 9.8E-05 mGy/MBq and a maximum fetal thyroid self dose of 3.5E-04 mGy/MBq.« less

Use of radiofrequency ablation in benign thyroid nodules: a literature review and updates.

PubMed

Wong, Kai-Pun; Lang, Brian Hung-Hin

2013-01-01

Successful thermal ablation using radiofrequency has been reported in various tumors including liver or kidney tumors. Nonsurgical minimally invasive ablative therapy such as radiofrequency ablation (RFA) has been reported to be a safe and efficient treatment option in managing symptomatic cold thyroid nodules or hyperfunctioning thyroid nodules. Pressure and cosmetic symptoms have been shown to be significantly improved both in the short and long terms after RFA. For hyperfunctioning thyroid nodules, RFA is indicated for whom surgery or radioiodine are not indicated or ineffective or for those who refuse surgery or radio-iodine. Improvement of thyroid function with decreased need for antithyroid medications has been reported. Complication rate is relatively low. By reviewing the current literature, we reported its efficacy and complications and compared the efficacy of RFA relative to other ablative options such as ethanol ablation and laser ablation.

Use of Radiofrequency Ablation in Benign Thyroid Nodules: A Literature Review and Updates

PubMed Central

Wong, Kai-Pun; Lang, Brian Hung-Hin

2013-01-01

Successful thermal ablation using radiofrequency has been reported in various tumors including liver or kidney tumors. Nonsurgical minimally invasive ablative therapy such as radiofrequency ablation (RFA) has been reported to be a safe and efficient treatment option in managing symptomatic cold thyroid nodules or hyperfunctioning thyroid nodules. Pressure and cosmetic symptoms have been shown to be significantly improved both in the short and long terms after RFA. For hyperfunctioning thyroid nodules, RFA is indicated for whom surgery or radioiodine are not indicated or ineffective or for those who refuse surgery or radio-iodine. Improvement of thyroid function with decreased need for antithyroid medications has been reported. Complication rate is relatively low. By reviewing the current literature, we reported its efficacy and complications and compared the efficacy of RFA relative to other ablative options such as ethanol ablation and laser ablation. PMID:24298282

Comparison of /sup 125/I-labeled and /sup 14/C-Labeled peptides of the major outer membrane protein of Chlamydia Trachomatis Strain L2/434 separated by high-performance liquid chromatography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Judd, R.C.; Caldwell, H.D.

1985-01-01

The objective of this study was to determine if in-gel chloramine-T radioiodination adequately labels OM proteins to allow for accurate and precise structural comparison of these molecules. Therefore, intrinsically /sup 14/C-amino acid labeled proteins and /sup 125/I-labeled proteins were cleaved with two endopeptidic reagents and the peptide fragments separated by HPLC. A comparison of retention times of the fragments, as determined by differential radiation counting, thus indicated whether /sup 125/Ilabeling identified of all the peptide peaks seen in the /sup 14/Clabeled proteins. Results demonstrated that radioiodination yields complete and accurate information about the primary structure of outer membrane proteins. Inmore » addition, it permits the use of extremely small amounts of protein allowing for method optimization and multiple separations to insure reproducibility.« less

Elucidation of a novel phenformin derivative on glucose-deprived stress responses in HT-29 cells.

PubMed

Oh-Hashi, Kentaro; Irie, Nao; Sakai, Takayuki; Okuda, Kensuke; Nagasawa, Hideko; Hirata, Yoko; Kiuchi, Kazutoshi

2016-08-01

Recently, we developed a variety of phenformin derivatives as selective antitumor agents. Based on previous findings, this study evaluated a promising compound, 2-(2-chlorophenyl)ethylbiguanide (2-Cl-Phen), on the basis of stress responses in the human colon cancer cell line HT-29 under a serum- and glucose-deprived condition. 2-Cl-Phen triggered morphological changes such as shrinkage and plasma membrane disintegration, as well as a decrease in mitochondrial activity and an increase in LDH leakage. To understand intracellular issues relating to 2-Cl-Phen, this study focused on the expression levels of ER stress-inducible genes and several oncogenic genes. Serum and glucose deprivation significantly induced a variety of ER stress-inducible genes, but a 12-h treatment of 2-Cl-Phen down-regulated expression of several ER stress-related genes, with the exception of GADD153. Interestingly, the expression levels of ATF6α, GRP78, MANF, and CRELD2 mRNA were almost completely decreased by 2-Cl-Phen. This study also observed that a 24-h treatment of 2-Cl-Phen attenuated the expression levels of GRP78, GADD153, and c-Myc protein. The decrease in c-Myc protein occurred before the fluctuation of GRP78 protein, while the expression of c-Myc mRNA showed little change with cotreatment of serum and glucose deprivation with 2-Cl-Phen. To further understand the 2-Cl-Phen-induced down-regulation of ATF6-related genes, this study investigated the stability of ATF6α and GRP78 proteins using NanoLuc-tagged constructs. The expression levels of NanoLuc-tagged ATF6α and GRP78 were significantly down-regulated by 2-Cl-Phen in the presence or absence of the translation inhibitor cycloheximide. Taken together, our novel phenformin derivative 2-Cl-Phen has the unique characteristic of diminishing tumor adaptive responses, especially the expression of ATF6-related genes, as well as that of c-Myc protein, in a transcriptional and posttranscriptional manner under a serum- and glucose-deprived condition. Further characterization of cytotoxic mechanisms related to phenformin derivatives may give new insights into developing additional promising anticancer agents.

Modification of glucose import capacity in Escherichia coli: physiologic consequences and utility for improving DNA vaccine production

PubMed Central

2013-01-01

Background The bacterium Escherichia coli can be grown employing various carbohydrates as sole carbon and energy source. Among them, glucose affords the highest growth rate. This sugar is nowadays widely employed as raw material in industrial fermentations. When E. coli grows in a medium containing non-limiting concentrations of glucose, a metabolic imbalance occurs whose main consequence is acetate secretion. The production of this toxic organic acid reduces strain productivity and viability. Solutions to this problem include reducing glucose concentration by substrate feeding strategies or the generation of mutant strains with impaired glucose import capacity. In this work, a collection of E. coli strains with inactive genes encoding proteins involved in glucose transport where generated to determine the effects of reduced glucose import capacity on growth rate, biomass yield, acetate and production of an experimental plasmid DNA vaccine (pHN). Results A group of 15 isogenic derivatives of E. coli W3110 were generated with single and multiple deletions of genes encoding glucose, mannose, beta-glucoside, maltose and N-acetylglucosamine components of the phosphoenolpyruvate:sugar phosphotransferase system (PTS), as well as the galactose symporter and the Mgl galactose/glucose ABC transporter. These strains were characterized by growing them in mineral salts medium supplemented with 2.5 g/L glucose. Maximum specific rates of glucose consumption (qs) spanning from 1.33 to 0.32 g/g h were displayed by the group of mutants and W3110, which resulted in specific growth rates ranging from 0.65-0.18 h-1. Acetate accumulation was reduced or abolished in cultures with all mutant strains. W3110 and five selected mutant derivatives were transformed with pHN. A 3.2-fold increase in pHN yield on biomass was observed in cultures of a mutant strain with deletion of genes encoding the glucose and mannose PTS components, as well as Mgl. Conclusions The group of E. coli mutants generated in this study displayed a reduction or elimination of overflow metabolism and a linear correlation between qs and the maximum specific growth rate as well as the acetate production rate. By comparing DNA vaccine production parameters among some of these mutants, it was possible to identify a near-optimal glucose import rate value for this particular application. The strains employed in this study should be a useful resource for studying the effects of different predefined qs values on production capacity for various biotechnological products. PMID:23638701

Positively charged gold nanoparticles capped with folate quaternary chitosan: Synthesis, cytotoxicity, and uptake by cancer cells.

PubMed

Yen, Hui-Ju; Young, Yen-An; Tsai, Tsung-Neng; Cheng, Kuang-Ming; Chen, Xin-An; Chen, Ying-Chuan; Chen, Cheng-Cheung; Young, Jenn-Jong; Hong, Po-da

2018-03-01

In this study, we synthesized various quaternary chitosan derivatives and used them to stabilize gold nanoparticles (AuNPs). These chitosan derivatives comprised N-(2-hydroxy)propyl-3-trimethylammonium chitosan chloride (HTCC), folate-HTCC, galactosyl-HTCC, and their fluorescein isothiocyanate-conjugated derivatives. Various positively surface-charged AuNPs were prepared under alkaline conditions using glucose as a reducing agent in the presence of the HTCC derivatives (HTCCs). The effects of the concentration of NaOH, glucose, and HTCCs on the particles size, zeta potential, and stability were studied in detail. Cell cycle assays verify that none of the HTCCs or HTCCs-AuNPs was cytotoxic to human umbilical vein endothelial cells. Flow cytometry analysis showed that the folate HTCC-AuNPs were internalized in Caco-2, HepG2, and HeLa cancer cells to a significantly greater extent than AuNPs without folate. But, galactosyl HTCC-AuNPs only showed high cell uptake by HepG2 cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

Stromal cell derived factor-1alpha protects stem cell derived insulin-producing cells from glucotoxicity under high glucose conditions in-vitro and ameliorates drug induced diabetes in rats

PubMed Central

2013-01-01

Background Diabetes mellitus is affecting more than 300 million people worldwide. Current treatment strategies cannot prevent secondary complications. Stem cells due to their regenerative power have long been the attractive target for the cell-based therapies. Mesenchymal stem cells (MSCs) possess the ability to differentiate into several cell types and to escape immune recognition in vitro. MSCs can be differentiated into insulin-producing cells (IPCs) and could be an exciting therapy for diabetes but problems like poor engraftment and survivability need to be confronted. It was hypothesized that stromal cell derived factor- 1alpha (SDF-1alpha) will enhance therapeutic potential of stem cell derived IPCs by increasing their survival and proliferation rate. Methods Novel culture conditions were developed to differentiate bone marrow derived mesenchymal stem cells (BMSCs) into IPCs by using endocrine differentiation inducers and growth factors via a three stage protocol. In order to enhance their therapeutic potential, we preconditioned IPCs with SDF-1alpha. Results Our results showed that SDF-1alpha increases survival and proliferation of IPCs and protects them from glucotoxicity under high glucose conditions in vitro. SDF-1alpha also enhances the glucose responsive insulin secretion in IPCs in vitro. SDF-1alpha preconditioning reverses hyperglycemia and increase serum insulin in drug induced diabetic rats. Conclusions The differentiation of BMSCs into IPCs and enhancement of their therapeutic potential by SDF-1alpha preconditioning may contribute to cell based therapies for diabetes. PMID:23648189

Cinnamic Acid and Its Derivatives: Mechanisms for Prevention and Management of Diabetes and Its Complications.

PubMed

Adisakwattana, Sirichai

2017-02-21

With recent insight into the development of dietary supplements and functional foods, search of effective phytochemical compounds and their mechanisms involved in prevention and management of diabetes and its complications are now being assessed. Cinnamic acid and its derivatives occur naturally in high levels of plant-based foods. Among various biological activities, cinnamic acid and its derivatives are associated with a beneficial influence on diabetes and its complications. The aim of the review is to summarize the potential mechanisms of these compounds for prevention and management of diabetes and its complications. Based on several in vitro studies and animal models, cinnamic acid and its derivatives act on different mechanism of actions, including stimulation of insulin secretion, improvement of pancreatic β-cell functionality, inhibition of hepatic gluconeogenesis, enhanced glucose uptake, increased insulin signaling pathway, delay of carbohydrate digestion and glucose absorption, and inhibition of protein glycation and insulin fibrillation. However, due to the limited intestinal absorption being a result of low bioavailability of cinnamic acid and its derivatives, current improvement efforts with entrapping into solid and liquid particles are highlighted. Further human clinical studies are needed to clarify the effects of cinnamic acid and its derivatives in diabetic patients.

Cinnamic Acid and Its Derivatives: Mechanisms for Prevention and Management of Diabetes and Its Complications

PubMed Central

Adisakwattana, Sirichai

2017-01-01

With recent insight into the development of dietary supplements and functional foods, search of effective phytochemical compounds and their mechanisms involved in prevention and management of diabetes and its complications are now being assessed. Cinnamic acid and its derivatives occur naturally in high levels of plant-based foods. Among various biological activities, cinnamic acid and its derivatives are associated with a beneficial influence on diabetes and its complications. The aim of the review is to summarize the potential mechanisms of these compounds for prevention and management of diabetes and its complications. Based on several in vitro studies and animal models, cinnamic acid and its derivatives act on different mechanism of actions, including stimulation of insulin secretion, improvement of pancreatic β-cell functionality, inhibition of hepatic gluconeogenesis, enhanced glucose uptake, increased insulin signaling pathway, delay of carbohydrate digestion and glucose absorption, and inhibition of protein glycation and insulin fibrillation. However, due to the limited intestinal absorption being a result of low bioavailability of cinnamic acid and its derivatives, current improvement efforts with entrapping into solid and liquid particles are highlighted. Further human clinical studies are needed to clarify the effects of cinnamic acid and its derivatives in diabetic patients. PMID:28230764

Adequate thyroid-stimulating hormone levels after levothyroxine discontinuation in the follow-up of patients with well-differentiated thyroid carcinoma.

PubMed

Sánchez, Reyna; Espinosa-de-los-Monteros, Ana Laura; Mendoza, Victoria; Brea, Eduardo; Hernández, Irma; Sosa, Ernesto; Mercado, Moisés

2002-01-01

In the follow-up of patients with well-differentiated thyroid carcinomas (WTC), a thyroid-stimulating hormone (TSH) >or=30 micro U/mL is generally accepted as adequate to perform whole body scans (WBS), determine thyroglobulin (Tg), and administer radioiodine therapeutically. These patients, inevitably rendered hypothyroid, are traditionally switched to T3 for 3-4 weeks prior to withdrawing all thyroid hormones for an additional 2-3 weeks. Neither TSH and Tg elevation dynamics nor WBS characteristics after simply interrupting L-T4 treatment without T3 administration have been evaluated. TSH, total T4 and T3, as well as FT4 were measured weekly after discontinuing L-T4 in 21 subjects (group I) and after thyroidectomy in 10 subjects (group II). WBS and Tg determination was performed upon achievement of TSH >or=30 micro U/mL. By the second week, 42% of group I patients and 70% of group II patients had TSH >or=30 micro U/mL. By the third week, 90% in group I and 100% in group II had achieved this target. Group I patients who needed 4 weeks to increase TSH received a greater cumulative radioiodine dose and had higher Tg levels. Positive WBS were found in eight cases and the incidence of a negative WBS with elevated Tg was significantly higher when evaluation occurred at the second week of L-T4 withdrawal compared to the fourth week. L-T4 interruption is a reasonable alternative to temporary T3 in preparation for radioiodine scanning and treatment.

Radioiodine (131I) therapies performed in a paediatric hospital: facilities and procedures.

PubMed

Bibbo, Giovanni; Benger, Tracy; Sigalas, Victoria; Kirkwood, Ian

2018-06-25

Radioiodine ( 131 I) therapies on younger children with thyroid cancer and neuroblastoma can be challenging as they are required to be isolated for a period of time due to radiation safety concerns. At our hospital these therapies are performed in a purpose-built child-friendly therapy room. Nursing staff are able to provide personal care during the isolation period with minimum radiation exposure. Patients are provided with various age-appropriate entertainment items such as iPad, X-Box, DVD, craft and books to keep them entertained while in isolation. Parents can communicate freely with their child via the audio-visual system located in the Ward Parent Lounge and can also stay in the shielded part of the ante room of the therapy room. Nursing staff can communicate with the patient via a similar audio-visual system located in the nurses station so that they only need to enter the therapy room when they are required to provide personal patient care. All persons entering the therapy room are monitored with personal digital dosimeters. Patients accept the isolation period with minimal aggravation and the personal radiation exposures to staff, parents and visitors are well below the general public annual limit of 1000 µSv. The design and facilities of the therapy room with its child-friendly surroundings and support network makes the experience of the isolation period easier and positive for both patients and parents. For Graves' disease, the patients are treated as outpatients in the Department of Nuclear Medicine and are discharged within a short time after the radioiodine administration.

Management of thyroid eye disease in the United Kingdom: A multi-centre thyroid eye disease audit.

PubMed

Mellington, F E; Dayan, C M; Dickinson, A J; Hickey, J L; MacEwen, C J; McLaren, J; Perros, P; Rose, G E; Uddin, J; Vaidya, B; Foley, P; Lazarus, J H; Mitchell, A; Ezra, D G

2017-06-01

This article aims to provide baseline data and highlight any major deficiencies in the current level of care provided for adult patients with thyroid eye disease (TED). We undertook a prospective, nonrandomized cross-sectional multicenter observational study. During a 3-month period June-August 2014, consecutive adult patients with TED who presented to nominated specialist eye clinics in the United Kingdom, completed a standardized questionnaire. Main outcome measures were: demographics, time from diagnosis to referral to tertiary centre, time from referral to review in specialist eye clinic, management of thyroid dysfunction, radioiodine and provision of steroid prophylaxis, smoking, and TED classification. 91 patients (mean age 47.88 years) were included. Female-to-male ratio was 6:1. Mean time since first symptoms of TED = 27.92 (73.71) months; from first visit to any doctor with symptoms to diagnosis = 9.37 (26.03) months; from hyperthyroidism diagnosis to euthyroidism 12.45 (16.81) months. First, 13% had received radioiodine. All those with active TED received prophylactic steroids. Seven patients who received radioiodine and did not have TED at the time went on to develop it. Then, 60% patients were current or ex-smokers. 63% current smokers had been offered smoking cessation advice. 65% patients had active TED; 4% had sight-threatening TED. A large proportion of patients (54%) were unaware of their thyroid status. Not enough patients are being provided with smoking cessation advice and information on the impact of smoking on TED and control of thyroid function.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao, Xuemei; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province; Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province

Thyroid cancer is a common malignancy of the endocrine system. Although radioiodine {sup 131}I treatment on differentiated thyroid cancer is widely used, many patients still fail to benefit from {sup 131}I therapy. Therefore, exploration of novel targeted therapies to suppress tumor growth and improve radioiodine uptake remains necessary. Bromodomain-containing protein 4 (BRD4) is an important member of the bromodomain and extra terminal domain family that influences transcription of downstream genes by binding to acetylated histones. In the present study, we found that BRD4 was up-regulated in thyroid cancer tissues and cell lines. Inhibition of BRD4 in thyroid cancer cells bymore » JQ1 resulted in cell cycle arrest at G0/G1 phase and enhanced {sup 131}I uptake in vitro and suppressed tumor growth in vivo. Moreover, JQ1 treatment suppressed C-MYC but enhanced NIS expression. We further demonstrated that BRD4 was enriched in the promoter region of C-MYC, which could be markedly blocked by JQ1 treatment. In conclusion, our findings revealed that the aberrant expression of BRD4 in thyroid cancer is possibly involved in tumor progression, and JQ1 is potentially an effective chemotherapeutic agent against human thyroid cancer. - Highlights: • BRD4 is upregulated in thyroid cancer tissues and cell lines. • Inhibition of BRD4 induced cell cycle arrest and enhanced radioiodine uptake in vitro and impaired tumor growth in vivo. • JQ1 suppressed the expression of C-MYC and promoted the expression of NIS and P21. • JQ1 attenuated the recruitment of BRD4 to MYC promoter in thyroid cancer.« less

Radioiodination of scorpion and snake toxins. [/sup 125/I, /sup 127/I

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rochat, H.; Tessier, M.; Miranda, F.

1977-10-01

Several scorpion and snake toxins were radioiodinated using the lactoperoxydase method of (/sup 125/I)iodide oxidation. Two techniques of labeling were set up: Using carrier-free Na/sup 125/I and 5 ..mu..g of toxin, about one iodine atom was incorporated per mole of protein without loss of toxicity. Specific radioactivities about 2,000 Ci/mmol (280 ..mu..Ci/..mu..g) were obtained. The modified toxin, purified by immunoprecipitation with an antiserum prepared against the native toxin, was obtained in a short time (4 hr), with a good yield (50 to 80%), and in a small volume (1 ml). Using Na/sup 127/I traced with Na /sup 125/I and largermore » amounts (200 ..mu..g) of toxin, more than one iodine atom was incorporated per mole of protein without loss of activity. Lower specific radioactivities (1 to 1.5 Ci/mmol) were obtained. The iodinated toxins were purified by gel filtration of the radioiodination mixtures on a column made of two layers of Sephadex (G-15 and G-50). The modified proteins were extensively analyzed by paper electrophoresis and polyacrylamide gel electrophoresis. Their content of monoiodotyrosine and diiodotyrosine was estimated and, in the case of toxin I of Androctonus australis Hector, it was possible to follow the iodination rate of its three tyrosine residues by automatic Edman degradation. The mode of purification of the iodinated scorpion toxins affects their behavior on molecular sieving on Sephadex G-50 and on electrophoresis on polyacrylamide gel. The results are discussed.« less

Animal models of disease: feline hyperthyroidism: an animal model for toxic nodular goiter.

PubMed

Peterson, Mark E

2014-11-01

Since first discovered just 35 years ago, the incidence of spontaneous feline hyperthyroidism has increased dramatically to the extent that it is now one of the most common disorders seen in middle-aged to senior domestic cats. Hyperthyroid cat goiters contain single or multiple autonomously (i.e. TSH-independent) functioning and growing thyroid nodules. Thus, hyperthyroidism in cats is clinically and histologically similar to toxic nodular goiter in humans. The disease in cats is mechanistically different from Graves' disease, because neither the hyperfunction nor growth of these nodules depends on extrathyroidal circulating stimulators. The basic lesion appears to be an excessive intrinsic growth capacity of some thyroid cells, but iodine deficiency, other nutritional goitrogens, or environmental disruptors may play a role in the disease pathogenesis. Clinical features of feline toxic nodular goiter include one or more palpable thyroid nodules, together with signs of hyperthyroidism (e.g. weight loss despite an increased appetite). Diagnosis of feline hyperthyroidism is confirmed by finding the increased serum concentrations of thyroxine and triiodothyronine, undetectable serum TSH concentrations, or increased thyroid uptake of radioiodine. Thyroid scintigraphy demonstrates a heterogeneous pattern of increased radionuclide uptake, most commonly into both thyroid lobes. Treatment options for toxic nodular goiter in cats are similar to that used in humans and include surgical thyroidectomy, radioiodine, and antithyroid drugs. Most authorities agree that ablative therapy with radioiodine is the treatment of choice for most cats with toxic nodular goiter, because the animals are older, and the disease will never go into remission. © 2014 Society for Endocrinology.

Safety regulations of food and water implemented in the first year following the Fukushima nuclear accident

PubMed Central

Hamada, Nobuyuki; Ogino, Haruyuki; Fujimichi, Yuki

2012-01-01

An earthquake and tsunami of historic proportions caused massive damage across the northeastern coast of Japan on the afternoon of 11 March 2011, and the release of radionuclides from the stricken reactors of the Fukushima nuclear power plant 1 was detected early on the next morning. High levels of radioiodines and radiocesiums were detected in the topsoil and plants on 15 March 2011, so sampling of food and water for monitoring surveys began on 16 March 2011. On 17 March 2011, provisional regulation values for radioiodine, radiocesiums, uranium, plutonium and other transuranic α emitters were set to regulate the safety of radioactively contaminated food and water. On 21 March 2011, the first restrictions on distribution and consumption of contaminated items were ordered. So far, tap water, raw milk, vegetables, mushrooms, fruit, nut, seaweeds, marine invertebrates, coastal fish, freshwater fish, beef, wild animal meat, brown rice, wheat, tea leaves and other foodstuffs had been contaminated above the provisional regulation values. The provisional regulation values for radioiodine were exceeded in samples taken from 16 March 2011 to 21 May 2011, and those for radiocesiums from 18 March 2011 to date. All restrictions were imposed within 318 days after the provisional regulation values were first exceeded for each item. This paper summarizes the policy for the execution of monitoring surveys and restrictions, and the outlines of the monitoring results of 220 411 samples and the enforced restrictions predicated on the information available as of 31 March 2012. PMID:22843368

[Efficacy of treatment with I(131) in paediatric Graves disease].

PubMed

Enes Romero, P; Martín-Frías, M; de Jesús, M; Caballero Loscos, C; Alonso Blanco, M; Barrio Castellanos, R

2014-01-01

Radioiodine is an important therapeutic option in young patients with Grave's disease (GD). In the United States it is a widespread therapy, but in Europe its use in paediatrics is still controversial. To report our experience in radioiodine therapy of paediatric GD patients and analyse its effectiveness and safety. We retrospectively studied our paediatric population (<18 years of age) with GD, diagnosed from 1982 to 2012. A curative option was offered to patients who did not respond to anti-thyroid drug (AT) at puberty. We analysed, the patient characteristics, TSH, T4, T3 and thyroid antibodies levels, AT response, remission post I(131), side effects, and hypothyroidism rates. A total of 50 patients were diagnosed with GD from 1982 to 2012. All patients received AT as initial treatment (mean duration: 35.3±25.9 months). Permanent remission was achieved in 46%. Thyroidectomy was performed in 5 patients, and 14 patients received I(131) (mean dose: 10.9±1.09 mCi). Remission with I(131) was obtained in 100%. The rate of permanent hypothyroidism was 90%. There was no progression of ophthalmopathy or side effects in any patients treated with I(131.) Radioiodine treatment of paediatric GD patients is safe, leads to complete remission at the expense of hypothyroidism, and does not exacerbate ophthalmopathy. It can be considered in patients older than 5 years, who do no not respond to AT or with significant side effects with this medication. Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

A glucose-centric perspective of hyperglycemia.

PubMed

Ramasarma, T; Rafi, M

2016-02-01

Digestion of food in the intestines converts the compacted storage carbohydrates, starch and glycogen, to glucose. After each meal, a flux of glucose (> 200 g) passes through the blood pool (4-6 g) in a short period of 2 h, keeping its concentration ideally in the range of 80-120 mg/100 mL. Tissue-specific glucose transporters (GLUTs) aid in the distribution of glucose to all tissues. The balance glucose after meeting the immediate energy needs is converted into glycogen and stored in liver (up to 100 g) and skeletal muscle (up to 300 g) for later use. High blood glucose gives the signal for increased release of insulin from pancreas. Insulin binds to insulin receptor on the plasma membrane and activates its autophosphorylation. This initiates the post-insulin-receptor signal cascade that accelerates synthesis of glycogen and triglyceride. Parallel control by phos-dephos and redox regulation of proteins exists for some of these steps. A major action of insulin is to inhibit gluconeogensis in the liver decreasing glucose output into blood. Cases with failed control of blood glucose have alarmingly increased since 1960 coinciding with changed life-styles and large scale food processing. Many of these turned out to be resistant to insulin, usually accompanied by dysfunctional glycogen storage. Glucose has an extended stay in blood at 8 mM and above and then indiscriminately adds on to surface protein-amino groups. Fructose in common sugar is 10-fold more active. This random glycation process interferes with the functions of many proteins (e.g., hemoglobin, eye lens proteins) and causes progressive damage to heart, kidneys, eyes and nerves. Some compounds are known to act as insulin mimics. Vanadium-peroxide complexes act at post-receptor level but are toxic. The fungus-derived 2,5-dihydroxybenzoquinone derivative is the first one known to act on the insulin receptor. The safe herbal products in use for centuries for glucose control have multiple active principles and targets. Some are effective in slowing formation of glucose in intestines by inhibiting α-glucosidases (e.g., salacia/saptarangi). Knowledge gained from French lilac on active guanidine group helped developing Metformin (1,1-dimethylbiguanide) one of the popular drugs in use. One strategy of keeping sugar content in diets in check is to use artificial sweeteners with no calories, no glucose or fructose and no effect on blood glucose (e.g., steviol, erythrytol). However, the three commonly used non-caloric artificial sweeteners, saccharin, sucralose and aspartame later developed glucose intolerance, the very condition they are expected to evade. Ideal way of keeping blood glucose under 6 mM and HbA1c, the glycation marker of hemoglobin, under 7% in blood is to correct the defects in signals that allow glucose flow into glycogen, still a difficult task with drugs and diets.

Diagnosis and treatment of Graves disease.

PubMed

Streetman, Darcie D; Khanderia, Ujjaini

2003-01-01

To review the etiology, diagnosis, and clinical presentation of Graves disease and provide an overview of the standard and adjunctive treatments. Specifically, antithyroid drugs, beta-blockers, inorganic iodide, lithium, and radioactive iodine are discussed, focusing on current controversies. Primary articles were identified through a MEDLINE search (1966-July 2000). Key word searches included beta-blockers, Graves disease, inorganic iodide, lithium, methimazole, and propylthiouracil. Additional articles from these sources and endocrinology textbooks were also identified. We agreed to include articles that would highlight the most relevant points, as well as current areas of controversy. Graves disease is the most common cause of hyperthyroidism. The 3 main treatment options for patients with Graves hyperthyroidism include antithyroid drugs, radioactive iodine, and surgery. Although the antithyroid drugs propylthiouracil (PTU) and methimazole (MMI) have similar efficacy, there are situations when 1 agent is preferred. MMI has a longer half-life than PTU, allowing once-daily dosing that can improve patient adherence to treatment. PTU has historically been the drug of choice for treating pregnant and breast-feeding women because of its limited transfer into the placenta and breast milk. Adjuvant therapies for Graves disease include beta-blockers, inorganic iodide, and lithium. beta-Blockers are used to decrease the symptoms of hyperthyroidism. Inorganic iodide is primarily used to prepare patients for thyroid surgery because of its ability to decrease the vascularity of the thyroid gland. Lithium, which acts in a manner similar to iodine, is not routinely used due to its transient effect and the risk of potentially serious adverse effects. In the US, radioiodine therapy has become the preferred treatment for adults with Graves disease. It is easy to administer, safe, effective, and more affordable than long-term treatment with antithyroid drugs. Hypothyroidism is an inevitable consequence of radioiodine therapy. Radioiodine is contraindicated in pregnant women because it can damage the fetal thyroid gland, resulting in fetal hypothyroidism. Bilateral subtotal thyroidectomy, which was once the only treatment available, is now performed only in special circumstances. In addition to the normal risks associated with surgery, laryngeal nerve damage, hypoparathyroidism, and hypothyroidism can occur following that procedure. Despite extensive experience with medical management, controversy prevails regarding choosing among the various drugs for treatment of Graves disease. None of the treatment options, including antithyroid drugs, radioiodine, and surgery, is ideal. Each has risks and benefits, and selection should be tailored to the individual patient.

Methods for Measuring Risk for Type 2 Diabetes in Youth: the Oral Glucose Tolerance Test (OGTT).

PubMed

Chen, Melinda E; Aguirre, Rebecca S; Hannon, Tamara S

2018-06-16

The oral glucose tolerance test (OGTT) is used both in clinical practice and research to assess glucose tolerance. In addition, the OGTT is utilized for surrogate measures of insulin sensitivity and the insulin response to enteral glucose and has been widely applied in the evaluation of β-cell dysfunction in obesity, prediabetes, and type 2 diabetes. Here we review the use of the OGTT and the OGTT-derived indices for measurement of risk markers for type 2 diabetes in youth. Advantages of using the OGTT for measures of diabetes risk include its accessibility and the incorporation of physiological contributions of the gut-pancreas axis in the measures of insulin response to glucose. Mathematical modeling expands the potential gains from the OGTT in physiology and clinical research. Disadvantages include individual differences in the rate of glucose absorption that modify insulin responses, imperfect control of the glycemic stimulus, and poor intraindividual reproducibility. Available research suggests the OGTT provides valuable information about the development of impaired glycemic control and β-cell function in obese youth along the spectrum of glucose tolerance.

Ability of higenamine and related compounds to enhance glucose uptake in L6 cells.

PubMed

Kato, Eisuke; Kimura, Shunsuke; Kawabata, Jun

2017-12-15

β2-Adrenergic receptor (β2AR) agonists are employed as bronchodilators to treat pulmonary disorders, but are attracting attention for their modulation of glucose handling and energy expenditure. Higenamine is a tetrahydroisoquinoline present in several plant species and has β2AR agonist activity, but the involvement of each functional groups in β2AR agonist activity and its effectiveness compared with endogenous catecholamines (dopamine, epinephrine, and norepinephrine) has rarely been studied. Glucose uptake of muscle cells are known to be induced through β2AR activation. Here, the ability to enhance glucose uptake of higenamine was compared with that of several methylated derivatives of higenamine or endogenous catecholamines. We found that: (i) the functional groups of higenamine except for the 4'-hydroxy group are required to enhance glucose uptake; (ii) higenamine shows a comparable ability to enhance glucose uptake with that of epinephrine and norepinephrine; (iii) the S-isomer shows a greater ability to enhance glucose uptake compared with that of the R-isomer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cloning and expression studies of the Dunaliella salina UDP-glucose dehydrogenase cDNA.

PubMed

Qinghua, He; Dairong, Qiao; Qinglian, Zhang; Shunji, He; Yin, Li; Linhan, Bai; Zhirong, Yang; Yi, Cao

2005-06-01

The enzyme UDP-glucose dehydrogenase (EC 1.1.1.22) converts UDP-glucose to UDP-glucuronate. Plant UDP-glucose dehydrogenase (UGDH) is an important enzyme in the formation of hemicellulose and pectin, the components of primary cell walls. A cDNA, named DsUGDH, (GeneBank accession number: AY795899) corresponding to UGDH was cloned by RT-PCR approach from Dunaliella salina. The cDNA is 1941-bp long and has an open reading frame encoded a protein of 483 amino acids with a calculated molecular weight of 53 kDa. The derived amino acids sequence shows high homology with reported plants UGDHs, and has highly conserved amino acids motifs believed to be NAD binding site and catalytic site. Although UDP-glucose dehydrogenase is a comparatively well characterized enzyme, the cloning and characterization of the green alga Dunaliella salina UDP-glucose dehydrogenase gene is very important to understand the salt tolerance mechanism of Dunaliella salina. Northern analyses indicate that NaCl can induce the expression the DsUGDH.

Performance Analysis of Fuzzy-PID Controller for Blood Glucose Regulation in Type-1 Diabetic Patients.

PubMed

Yadav, Jyoti; Rani, Asha; Singh, Vijander

2016-12-01

This paper presents Fuzzy-PID (FPID) control scheme for a blood glucose control of type 1 diabetic subjects. A new metaheuristic Cuckoo Search Algorithm (CSA) is utilized to optimize the gains of FPID controller. CSA provides fast convergence and is capable of handling global optimization of continuous nonlinear systems. The proposed controller is an amalgamation of fuzzy logic and optimization which may provide an efficient solution for complex problems like blood glucose control. The task is to maintain normal glucose levels in the shortest possible time with minimum insulin dose. The glucose control is achieved by tuning the PID (Proportional Integral Derivative) and FPID controller with the help of Genetic Algorithm and CSA for comparative analysis. The designed controllers are tested on Bergman minimal model to control the blood glucose level in the facets of parameter uncertainties, meal disturbances and sensor noise. The results reveal that the performance of CSA-FPID controller is superior as compared to other designed controllers.

Neurotrophin Signaling Is Required for Glucose-Induced Insulin Secretion.

PubMed

Houtz, Jessica; Borden, Philip; Ceasrine, Alexis; Minichiello, Liliana; Kuruvilla, Rejji

2016-11-07

Insulin secretion by pancreatic islet β cells is critical for glucose homeostasis, and a blunted β cell secretory response is an early deficit in type 2 diabetes. Here, we uncover a regulatory mechanism by which glucose recruits vascular-derived neurotrophins to control insulin secretion. Nerve growth factor (NGF), a classical trophic factor for nerve cells, is expressed in pancreatic vasculature while its TrkA receptor is localized to islet β cells. High glucose rapidly enhances NGF secretion and increases TrkA phosphorylation in mouse and human islets. Tissue-specific deletion of NGF or TrkA, or acute disruption of TrkA signaling, impairs glucose tolerance and insulin secretion in mice. We show that internalized TrkA receptors promote insulin granule exocytosis via F-actin reorganization. Furthermore, NGF treatment augments glucose-induced insulin secretion in human islets. These findings reveal a non-neuronal role for neurotrophins and identify a new regulatory pathway in insulin secretion that can be targeted to ameliorate β cell dysfunction. Copyright © 2016 Elsevier Inc. All rights reserved.

[Biocompatibility of peritoneal dialysis fluids].

PubMed

Boulanger, Eric; Moranne, Olivier; Wautier, Marie-Paule; Rougier, Jean-Phillipe; Ronco, Pierre; Pagniez, Dominique; Wautier, Jean-Luc

2005-03-01

Repeated and long-term exposure to conventional glucose-based peritoneal dialysis fluids (PDFs) with poor biocompatibility plays a central role in the pathogenesis of the functional and structural changes of the peritoneal membrane. We have used immortalized human peritoneal mesothelial cells in culture to assess in vitro the biocompatibility of PDFs. Low pH, high glucose concentration and heat sterilization represent major factors of low biocompatibility. Two recent groups of glucose derivatives have been described. Glucose degradation products (GDPs) are formed during heat sterilization (glycoxidation) and storage. GDPs can bind protein and form AGEs (Advanced Glycation End-products), which can also result from the binding of glucose to free NH2 residues of proteins (glycation). The physiological pH, and the separation of glucose during heat sterilization (low GDP content) in the most recent PDFs dramatically increase the biocompatibility. The choice of PD programs with high biocompatibility PDFs allows preserving the function of the peritoneal membrane. Improvement of PDF biocompatibility may limit the occurrence of chronic chemical peritonitis and may allow long-term PD treatment.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Redies, C.; Hoffer, L.J.; Beil, C.

In prolonged fasting, the brain derives a large portion of its oxidative energy from the ketone bodies, beta-hydroxybutyrate and acetoacetate, thereby reducing whole body glucose consumption. Energy substrate utilization differs regionally in the brain of fasting rat, but comparable information has hitherto been unavailable in humans. We used positron emission tomography (PET) to study regional brain glucose and oxygen metabolism, blood flow, and blood volume in four obese subjects before and after a 3-wk total fast. Whole brain glucose utilization fell to 54% of control (postabsorptive) values (P less than 0.002). The whole brain rate constant for glucose tracer phosphorylationmore » fell to 51% of control values (P less than 0.002). Both parameters decreased uniformly throughout the brain. The 2-fluoro-2-deoxy-D-glucose lumped constant decreased from a control value of 0.57 to 0.43 (P less than 0.01). Regional blood-brain barrier transfer coefficients for glucose tracer, regional oxygen utilization, blood flow, and blood volume were unchanged.« less

Asymmetric distribution of glucose and indole-3-acetyl-myo-inositol in geostimulated Zea mays seedlings

NASA Technical Reports Server (NTRS)

Momonoki, Y. S.; Bandurski, R. S. (Principal Investigator)

1988-01-01

Indole-3-acetyl-myo-inositol occurs in both the kernel and vegetative shoot of germinating Zea mays seedlings. The effect of a gravitational stimulus on the transport of [3H]-5-indole-3-acetyl-myo-inositol and [U-14C]-D-glucose from the kernel to the seedling shoot was studied. Both labeled glucose and labeled indole-3-acetyl-myo-inositol become asymmetrically distributed in the mesocotyl cortex of the shoot with more radioactivity occurring in the bottom half of a horizontally placed seedling. Asymmetric distribution of [3H]indole-3-acetic acid, derived from the applied [3H]indole-3-acetyl-myo-inositol, occurred more rapidly than distribution of total 3H-radioactivity. These findings demonstrate that the gravitational stimulus can induce an asymmetric distribution of substances being transported from kernel to shoot. They also indicate that, in addition to the transport asymmetry, gravity affects the steady state amount of indole-3-acetic acid derived from indole-3-acetyl-myo-inositol.

Integration of Chemical and Biological Catalysis: Production of Furylglycolic Acid from Glucose via Cortalcerone

Treesearch

Thomas J. Schwartz; Samuel M. Goodman; Christian M. Osmundsen; Esben Taarning; Michael D. Mozuch; Jill Gaskell; Daniel Cullen; Philip J. Kersten; James A. Dumesic

2013-01-01

Furylglycolic acid (FA), a pseudoaromatic hydroxy-acid suitable for copolymerization with lactic acid, can be produced from glucose via enzymatically derived cortalcerone using a combination of Brønsted and Lewis acid catalysts. Cortalcerone is first converted to furylglyoxal hydrate (FH) over a Brønsted acid site (HCl or Al-containing betazeolite), and FH is...

Retrospective dose assessment for the population living in areas of local fallout from the Semipalatinsk Nuclear Test Site Part II: Internal exposure to thyroid.

PubMed

Gordeev, Konstantin; Shinkarev, Sergey; Ilyin, Leonid; Bouville, André; Hoshi, Masaharu; Luckyanov, Nickolas; Simon, Steven L

2006-02-01

A methodology to assess internal exposure to thyroid from radioiodines for the residents living in settlements located in the vicinity of the Semipalatinsk Nuclear Test Site is described that is the result of many years of research, primarily at the Moscow Institute of Biophysics. This methodology introduces two important concepts. First, the biologically active fraction, is defined as the fraction of the total activity on fallout particles with diameter less than 50 microns. That fraction is retained by vegetation and will ultimately result in contamination of dairy products. Second, the relative distance is derived as a dimensionless quantity from information on test yield, maximum height of cloud, and average wind velocity and describes how the biologically active fraction is distributed with distance from the site of the explosion. The parameter is derived in such a way that at locations with equal values of relative distance, the biologically active fraction will be the same for any test. The estimates of internal exposure to thyroid for the residents of Dolon and Kanonerka villages, for which the external exposure were assessed and given in a companion paper (Gordeev et al. 2006) in this conference, are presented. The main sources of uncertainty in the estimates are identified.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kahoun, J.R.; Ruoho, A.E.

A carrier-free radioiodinated cocaine photoaffinity label, (-)-3-({sup 125}I)iodo-4-azidococaine (({sup 125}I)IACoc), has been synthesized and used as a probe for cocaine-binding proteins. Photoaffinity labeling with 0.5 nM ({sup 125}I)IACoc resulted in selective derivatization of a 26-kDa polypeptide with the pharmacology of a sigma receptor in membranes derived from whole rat brain, rat liver, and human placenta. ({sup 125}I)IACoc labeling of the 26-kDa polypeptide was also inhibited by 10 {mu}M imipramine, amitriptyline, fluoxetine, benztropine, and tetrabenazine. The size of the ({sup 125}I)I-ACoc-labeled proteins is consistent with the size of proteins photolabeled in guinea pig brain and liver membranes by using the sigmamore » photolabel azido-({sup 3}H)DTG. Kinetic analysis of ({sup 125}I)IACoc binding to rat liver microsomes revealed two sites with K{sub d} values of 19 and 126 pM, respectively. The presence or absence of proteolytic inhibitors during membrane preparation did not alter the size of the photolabeled sigma receptor, indicating that the 26-kDa polypeptide was not derived from a larger protein. In summary, ({sup 125}I)IACoc is a potent and highly specific photoaffinity label for the haloperidol-sensitive sigma receptor and will be useful for its biochemical and molecular characterization.« less

Endothelial cell membrane vesicles in the study of organ preference of metastasis.

PubMed

Johnson, R C; Augustin-Voss, H G; Zhu, D Z; Pauli, B U

1991-01-01

Many malignancies exhibit distinct patterns of metastasis that appear to be mediated by receptor/ligand-like interactions between tumor cells and organ-specific vascular endothelium. In order to study endothelial cell surface molecules involved in the binding of metastatic cells, we developed a perfusion method to isolate outside-out membrane vesicles from the lumenal surface of rat lung microvascular endothelium. Lungs were perfused in situ for 4 h at 37 degrees C with a solution of 100 mM formaldehyde, 2 mM dithiothreitol in phosphate-buffered saline to induce endothelial cell vesiculation. Radioiodinated rat lung endothelial cell membrane vesicles bound lung-metastatic tumor cells (B16F10, R323OAC-MET) in significantly higher numbers than their low or nonmetastatic counterparts (B16F0, R323OAC-LR). In contrast, leg endothelial membrane vesicle showed no binding preference for either cell line. Neuraminidase treatment of vesicles abolished specificity of adhesion of lung-derived vesicles to lung metastatic tumor cells. These results demonstrate that in situ perfusion is an appropriate technique to obtain pure endothelial cell membrane vesicles containing functionally active adhesion molecules. The preferential binding of lung-derived endothelial cell membrane vesicles by lung metastatic tumor cells is evidence of the importance of endothelial cell adhesion molecules in the formation of metastases.

Methamphetamine Inhibits the Glucose Uptake by Human Neurons and Astrocytes: Stabilization by Acetyl-L-Carnitine

PubMed Central

Szlachetka, Adam M.; Haorah, James

2011-01-01

Methamphetamine (METH), an addictive psycho-stimulant drug exerts euphoric effects on users and abusers. It is also known to cause cognitive impairment and neurotoxicity. Here, we hypothesized that METH exposure impairs the glucose uptake and metabolism in human neurons and astrocytes. Deprivation of glucose is expected to cause neurotoxicity and neuronal degeneration due to depletion of energy. We found that METH exposure inhibited the glucose uptake by neurons and astrocytes, in which neurons were more sensitive to METH than astrocytes in primary culture. Adaptability of these cells to fatty acid oxidation as an alternative source of energy during glucose limitation appeared to regulate this differential sensitivity. Decrease in neuronal glucose uptake by METH was associated with reduction of glucose transporter protein-3 (GLUT3). Surprisingly, METH exposure showed biphasic effects on astrocytic glucose uptake, in which 20 µM increased the uptake while 200 µM inhibited glucose uptake. Dual effects of METH on glucose uptake were paralleled to changes in the expression of astrocytic glucose transporter protein-1 (GLUT1). The adaptive nature of astrocyte to mitochondrial β-oxidation of fatty acid appeared to contribute the survival of astrocytes during METH-induced glucose deprivation. This differential adaptive nature of neurons and astrocytes also governed the differential sensitivity to the toxicity of METH in these brain cells. The effect of acetyl-L-carnitine for enhanced production of ATP from fatty oxidation in glucose-free culture condition validated the adaptive nature of neurons and astrocytes. These findings suggest that deprivation of glucose-derived energy may contribute to neurotoxicity of METH abusers. PMID:21556365

Glucose-responsive hydrogel electrode for biocompatible glucose transistor

NASA Astrophysics Data System (ADS)

Kajisa, Taira; Sakata, Toshiya

2017-12-01

In this paper, we propose a highly sensitive and biocompatible glucose sensor using a semiconductor-based field effect transistor (FET) with a functionalized hydrogel. The principle of the FET device contributes to the easy detection of ionic charges with high sensitivity, and the hydrogel coated on the electrode enables the specific detection of glucose with biocompatibility. The copolymerized hydrogel on the Au gate electrode of the FET device is optimized by controlling the mixture ratio of biocompatible 2-hydroxyethylmethacrylate (HEMA) as the main monomer and vinylphenylboronic acid (VPBA) as a glucose-responsive monomer. The gate surface potential of the hydrogel FETs shifts in the negative direction with increasing glucose concentration from 10 μM to 40 mM, which results from the increase in the negative charges on the basis of the diol-binding of PBA derivatives with glucose molecules in the hydrogel. Moreover, the hydrogel coated on the gate suppresses the signal noise caused by the nonspecific adsorption of proteins such as albumin. The hydrogel FET can serve as a highly sensitive and biocompatible glucose sensor in in vivo or ex vivo applications such as eye contact lenses and sheets adhering to the skin.

Development of glucose measurement system based on pulsed laser-induced ultrasonic method

NASA Astrophysics Data System (ADS)

Ren, Zhong; Wan, Bin; Liu, Guodong; Xiong, Zhihua

2016-09-01

In this study, a kind of glucose measurement system based on pulsed-induced ultrasonic technique was established. In this system, the lateral detection mode was used, the Nd: YAG pumped optical parametric oscillator (OPO) pulsed laser was used as the excitation source, the high sensitivity ultrasonic transducer was used as the signal detector to capture the photoacoustic signals of the glucose. In the experiments, the real-time photoacoustic signals of glucose aqueous solutions with different concentrations were captured by ultrasonic transducer and digital oscilloscope. Moreover, the photoacoustic peak-to-peak values were gotten in the wavelength range from 1300nm to 2300nm. The characteristic absorption wavelengths of glucose were determined via the difference spectral method and second derivative method. In addition, the prediction models of predicting glucose concentrations were established via the multivariable linear regression algorithm and the optimal prediction model of corresponding optimal wavelengths. Results showed that the performance of the glucose system based on the pulsed-induced ultrasonic detection method was feasible. Therefore, the measurement scheme and prediction model have some potential value in the fields of non-invasive monitoring the concentration of the glucose gradient, especially in the food safety and biomedical fields.

Muscarinic receptor subtype selectivity of novel heterocyclic QNB analogues

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baumgold, J.; Cohen, V.I.; Paek, R.

1991-01-01

In an effort at synthesizing centrally-active subtype-selective antimuscarinic agents, the authors derivatized QNB (quinuclidinyl benzilate), a potent muscarinic antagonist, by replacing one of the phenyl groups with less lipophilic heterocyclic moieties. The displacement of ({sup 3}H)-N-methyl scopolamine binding by these novel compounds to membranes from cells expressing ml - m4 receptor subtypes was determined. Most of the novel 4-bromo-QNB analogues were potent and slightly selective for ml receptors. The 2-thienyl derivative was the most potent, exhibiting a 2-fold greater potency than BrQNB at ml receptors, and a 4-fold greater potency than BrQNB at ml receptors, and a 4-fold greater potencymore » at m2 receptors. This compound was also considerably less lipophilic than BrQNB as determined from its retention time on C18 reverse phase HPLC. This compound may therefore be useful both for pharmacological studies and as a candidate for a radioiodinated SPECT imaging agent for ml muscarinic receptors in human brain.« less

Enhanced tumor retention of a radiohalogen label for site-specific modification of antibodies.

PubMed

Boswell, C Andrew; Marik, Jan; Elowson, Michael J; Reyes, Noe A; Ulufatu, Sheila; Bumbaca, Daniela; Yip, Victor; Mundo, Eduardo E; Majidy, Nicholas; Van Hoy, Marjie; Goriparthi, Saritha N; Trias, Anthony; Gill, Herman S; Williams, Simon P; Junutula, Jagath R; Fielder, Paul J; Khawli, Leslie A

2013-12-12

A known limitation of iodine radionuclides for labeling and biological tracking of receptor targeted proteins is the tendency of iodotyrosine to rapidly diffuse from cells following endocytosis and lysosomal degradation. In contrast, radiometal-chelate complexes such as indium-111-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (In-111-DOTA) accumulate within target cells due to the residualizing properties of the polar, charged metal-chelate-amino acid adduct. Iodine radionuclides boast a diversity of nuclear properties and chemical means for incorporation, prompting efforts to covalently link radioiodine with residualizing molecules. Herein, we describe the Ugi-assisted synthesis of [I-125]HIP-DOTA, a 4-hydroxy-3-iodophenyl (HIP) derivative of DOTA, and demonstration of its residualizing properties in a murine xenograft model. Overall, this study displays the power of multicomponent synthesis to yield a versatile radioactive probe for antibodies across multiple therapeutic areas with potential applications in both preclinical biodistribution studies and clinical radioimmunotherapies.

The Ligand Binding Region of the Sigma-1 Receptor: Studies Utilizing Photoaffinity Probes, Sphingosine and N-Alkylamines

PubMed Central

Ruoho, Arnold E.; Chu, Uyen B.; Ramachandran, Subramaniam; Fontanilla, Dominique; Mavlyutov, Timur; Hajipour, Abdol R.

2015-01-01

The sigma-1 receptor is a 26 kDa endoplasmic reticulum resident membrane protein that has been shown to have chaperone activity in addition to its promiscuous binding to pharmacological agents. Ligand binding domain(s) of the sigma-1 receptor have been identified using the E. coli expressed and purified receptor protein and novel radioiodinated azido photoaffinity probes followed by pro-teolytic and chemical cleavage strategies. The outcome of these experiments indicates that the sigma-1 receptor ligand binding regions are formed primarily by juxtaposition of its second and third hydrophobic domains, regions where the protein shares considerable homology with the fungal enzyme, sterol isomerase that is essential for the biosynthesis of ergosterol. Data indicate that these hydrophobic steroid binding domain like (SBDL) regions on the sigma-1 receptor are likely to interact selectively with N-alkyl amines such as the endogenous sphingolipids and with synthetic N-alkylamines and N-aralkylamines derivatives. A proposed model for the sigma-1 receptor is presented. PMID:22288412

Radiolabeled probes for imaging Alzheimer’s plaques

NASA Astrophysics Data System (ADS)

Kulkarni, P. V.; Arora, V.; Roney, A. C.; White, C.; Bennett, M.; Antich, P. P.; Bonte, F. J.

2005-12-01

Alzheimer's disease (AD) is a debilitating disease characterized by the presence of extra-cellular plaques and intra-cellular neurofibrillary tangles (NFTs) in the brain. The major protein component of these plaques is beta amyloid peptide (Aβ), a 40-42 amino acid peptide cleaved from amyloid precursor protein (APP) by β-secretase and a putative γ-secretase. We radioiodinated quinoline derivatives (clioquinol and oxine) and evaluated them as potential amyloid imaging agents based on their ability to cross the blood brain barrier (BBB) and on their selectivity to metal binding sites on amyloid plaques. The uptake of theses tracers in the brains of normal swiss-webster mice was rapid and so was the clearance. Selectivity was demonstrated by higher binding to AD brain homogenates compared to normal brain. Autoradiographic studies demonstrated the localization of the tracers in the plaque regions of the AD brain sections as well as in liver tissue with amyloidosis. Further optimization and evaluations would likely lead to development of these molecules as AD plaque imaging agents.

Alkali Metal-Glucose Interaction Probed with Infrared Pre-Dissociation Spectroscopy

NASA Astrophysics Data System (ADS)

Kregel, Steven J.; Marsh, Brett; Zhou, Jia; Garand, Etienne

2015-06-01

The efficient extraction of cellulose from biomass and its subsequent conversion to glucose derivatives is an attractive goal in the field of energy science. However, current industrial methods require high ionic strength and harsh conditions. Ionic liquids (IL's) are a class of "green" compounds that have been shown to dissolve cellulose in concentrations of up to 25 wt%. In order to understand IL's extraordinary cellulose dissolving power, a molecular level understanding of the IL-cellulose interaction is needed. Toward that end, we have acquired infrared pre-dissociation spectra of M+-glucose, where M+=Li+, Na+, or K+. Through comparisons with density functional theory calculations, we have determined the relative abundances of various M+-glucose binding motifs in both the thermodynamic and kinetic limits. These results provide insight on the hydrogen bonding dynamics of glucose and are a step towards a fuller understanding of cellulose interactions with ionic liquids.

Glucose kinetics in infants of diabetic mothers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cowett, R.M.; Susa, J.B.; Giletti, B.

1983-08-01

Glucose kinetic studies were performed to define the glucose turnover rate with 78% enriched D-(U-13C) glucose by the prime constant infusion technique at less than or equal to 6 hours of age in nine infants of diabetic mothers (four insulin-dependent and five chemical diabetic patients) at term. Five normal infants were studied as control subjects. All infants received 0.9% saline intravenously during the study with the tracer. Fasting plasma glucose, insulin, and glucose13/12C ratios were measured during the steady state, and the glucose turnover rate was derived. The average plasma glucose concentration was similar during the steady state in themore » infants of the diabetic mothers and in the control infants, and the glucose turnover rate was not significantly different among the groups: 2.3 +/- 0.6 mg . kg-1 min-1 in infants of insulin-dependent diabetic patients; 2.4 +/- 0.4 mg . kg-1 min-1 in infants of chemical diabetic patients; and 3.2 +/- 0.3 mg . kg-1 min-1 in the control subjects. Good control of maternal diabetes evidenced by the normal maternal hemoglobin A1c and plasma glucose concentration at delivery and cord plasma glucose concentration resulted in glucose kinetic values in the infants of diabetic mothers that were indistinguishable from those of control subjects. The data further support the importance of good control of the diabetic state in the pregnant woman to minimize or prevent neonatal hypoglycemia.« less

Acute activation of GLP-1-expressing neurons promotes glucose homeostasis and insulin sensitivity.

PubMed

Shi, Xuemei; Chacko, Shaji; Li, Feng; Li, Depei; Burrin, Douglas; Chan, Lawrence; Guan, Xinfu

2017-11-01

Glucagon-like peptides are co-released from enteroendocrine L cells in the gut and preproglucagon (PPG) neurons in the brainstem. PPG-derived GLP-1/2 are probably key neuroendocrine signals for the control of energy balance and glucose homeostasis. The objective of this study was to determine whether activation of PPG neurons per se modulates glucose homeostasis and insulin sensitivity in vivo. We generated glucagon (Gcg) promoter-driven Cre transgenic mice and injected excitatory hM3Dq-mCherry AAV into their brainstem NTS. We characterized the metabolic impact of PPG neuron activation on glucose homeostasis and insulin sensitivity using stable isotopic tracers coupled with hyperinsulinemic euglycemic clamp. We showed that after ip injection of clozapine N-oxide, Gcg-Cre lean mice transduced with hM3Dq in the brainstem NTS downregulated basal endogenous glucose production and enhanced glucose tolerance following ip glucose tolerance test. Moreover, acute activation of PPG neurons NTS enhanced whole-body insulin sensitivity as indicated by increased glucose infusion rate as well as augmented insulin-suppression of endogenous glucose production and gluconeogenesis. In contrast, insulin-stimulation of glucose disposal was not altered significantly. We conclude that acute activation of PPG neurons in the brainstem reduces basal glucose production, enhances intraperitoneal glucose tolerance, and augments hepatic insulin sensitivity, suggesting an important physiological role of PPG neurons-mediated circuitry in promoting glycemic control and insulin sensitivity. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

Evidence that forskolin binds to the glucose transporter of human erythrocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lavis, V.R.; Lee, D.P.; Shenolikar, S.

1987-10-25

Binding of (4-/sup 3/H)cytochalasin B and (12-/sup 3/H)forskolin to human erythrocyte membranes was measured by a centrifugation method. Glucose-displaceable binding of cytochalasin B was saturable, with KD = 0.11 microM, and maximum binding approximately 550 pmol/mg of protein. Forskolin inhibited the glucose-displaceable binding of cytochalasin B in an apparently competitive manner, with K1 = 3 microM. Glucose-displaceable binding of (12-/sup 3/H)forskolin was also saturable, with KD = 2.6 microM and maximum binding approximately equal to 400 pmol/mg of protein. The following compounds inhibited binding of (12-/sup 3/H)forskolin and (4-/sup 3/H)cytochalasin B equivalently, with relative potencies parallel to their reported affinitiesmore » for the glucose transport system: cytochalasins A and D, dihydrocytochalasin B, L-rhamnose, L-glucose, D-galactose, D-mannose, D-glucose, 2-deoxy-D-glucose, 3-O-methyl-D-glucose, phloretin, and phlorizin. A water-soluble derivative of forskolin, 7-hemisuccinyl-7-desacetylforskolin, displaced equivalent amounts of (4-/sup 3/H)cytochalasin B or (12-/sup 3/H)forskolin. Rabbit erythrocyte membranes, which are deficient in glucose transporter, did not bind either (4-/sup 3/H)cytochalasin B or (12-/sup 3/H)forskolin in a glucose-displaceable manner. These results indicate that forskolin, in concentrations routinely employed for stimulation of adenylate cyclase, binds to the glucose transporter. Endogenous ligands with similar specificities could be important modulators of cellular metabolism.« less

Central Composite Design (CCD) applied for statistical optimization of glucose and sucrose binary carbon mixture in enhancing the denitrification process

NASA Astrophysics Data System (ADS)

Lim, Jun-Wei; Beh, Hoe-Guan; Ching, Dennis Ling Chuan; Ho, Yeek-Chia; Baloo, Lavania; Bashir, Mohammed J. K.; Wee, Seng-Kew

2017-11-01

The present study provides an insight into the optimization of a glucose and sucrose mixture to enhance the denitrification process. Central Composite Design was applied to design the batch experiments with the factors of glucose and sucrose measured as carbon-to-nitrogen (C:N) ratio each and the response of percentage removal of nitrate-nitrogen (NO3 --N). Results showed that the polynomial regression model of NO3 --N removal had been successfully derived, capable of describing the interactive relationships of glucose and sucrose mixture that influenced the denitrification process. Furthermore, the presence of glucose was noticed to have more consequential effect on NO3 --N removal as opposed to sucrose. The optimum carbon sources mixture to achieve complete removal of NO3 --N required lesser glucose (C:N ratio of 1.0:1.0) than sucrose (C:N ratio of 2.4:1.0). At the optimum glucose and sucrose mixture, the activated sludge showed faster acclimation towards glucose used to perform the denitrification process. Later upon the acclimation with sucrose, the glucose uptake rate by the activated sludge abated. Therefore, it is vital to optimize the added carbon sources mixture to ensure the rapid and complete removal of NO3 --N via the denitrification process.

High glucose environment inhibits cranial neural crest survival by activating excessive autophagy in the chick embryo

PubMed Central

Wang, Xiao-Yu; Li, Shuai; Wang, Guang; Ma, Zheng-Lai; Chuai, Manli; Cao, Liu; Yang, Xuesong

2015-01-01

High glucose levels induced by maternal diabetes could lead to defects in neural crest development during embryogenesis, but the cellular mechanism is still not understood. In this study, we observed a defect in chick cranial skeleton, especially parietal bone development in the presence of high glucose levels, which is derived from cranial neural crest cells (CNCC). In early chick embryo, we found that inducing high glucose levels could inhibit the development of CNCC, however, cell proliferation was not significantly involved. Nevertheless, apoptotic CNCC increased in the presence of high levels of glucose. In addition, the expression of apoptosis and autophagy relevant genes were elevated by high glucose treatment. Next, the application of beads soaked in either an autophagy stimulator (Tunicamycin) or inhibitor (Hydroxychloroquine) functionally proved that autophagy was involved in regulating the production of CNCC in the presence of high glucose levels. Our observations suggest that the ERK pathway, rather than the mTOR pathway, most likely participates in mediating the autophagy induced by high glucose. Taken together, our observations indicated that exposure to high levels of glucose could inhibit the survival of CNCC by affecting cell apoptosis, which might result from the dysregulation of the autophagic process. PMID:26671447

Design and preparation of open circuit potential biosensor for in vitro and in vivo glucose monitoring.

PubMed

Song, Yonggui; Su, Dan; Shen, Yuan; Liu, Hongyu; Wang, Li

2017-01-01

A novel open circuit potential biosensor (OCPS) composed of a working electrode and a Ag/AgCl reference electrode was designed for in vivo continuous glucose monitoring in this work. The macroporous carbon derived from kenaf stem (KSC) was used to construct a KSC microelectrode (denoted as KSCME) which was subsequently used to load glucose oxidase (GOD) as the working electrode. The resulting GOD/KSCMEs could catalyze the oxidation of glucose directly to result in changes of the open circuit potential (V oc ) of the OCPS. The V oc of OCPS was dependent on the glucose concentration, showing a linear range of 0.03-10.0 mM (R = 0.999) with a detection limit of 10 μM. In addition, the OCPS exhibited good selectivity for glucose over other common endogenous interferences. The feasibility of the proposed OCPS for glucose detection in mice skin tumors and normal tissue homogenate samples (in vitro experiment) and rat subcutaneous glucose monitoring (in vivo experiment) was also demonstrated with satisfactory results. The biosensor represents a novel example of a superficial cancer diagnostic device, and the proposed OCPS also provides new ideas for the development of a simple and highly selective device for continuous glucose sensing.

Biological activity studies of the novel glucagon-like peptide-1 derivative HJ07.

PubMed

Han, Jing; Sun, Li-Dan; Qian, Hai; Huang, Wen-Long

2014-08-01

To identify the glucose lowering ability and chronic treatment effects of a novel coumarin-glucagon-like peptide-1 (GLP-1) conjugate HJ07. A receptor activation experiment was performed in HEK 293 cells and the glucose lowering ability was evaluated with hypoglycemic duration and glucose stabilizing tests. Chronic treatment was performed by daily injection of exendin-4, saline, and HJ07. Body weight and HbA1c were measured every week, and an intraperitoneal glucose tolerance test was performed before treatment and after treatment. HJ07 showed well-preserved receptor activation efficacy. The hypoglycemic duration test showed that HJ07 possessed a long-acting, glucose-lowering effect and the glucose stabilizing test showed that the antihyperglycemic activity of HJ07 was still evident at a predetermined time (12 h) prior to the glucose challenge (0 h). The long time glucose-lowering effect of HJ07 was better than native GLP-1 and exendin-4. Furthermore, once daily injection of HJ07 to db/db mice achieved long-term beneficial effects on HbA1c lowering and glucose tolerance. The biological activity results of HJ07 suggest that HJ07 is a potential long-acting agent for the treatment of type 2 diabetes. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Separation of saccharides derivatized with 2-aminobenzoic acid by capillary electrophoresis and their structural consideration by nuclear magnetic resonance.

PubMed

He, Liping; Sato, Kae; Abo, Mitsuru; Okubo, Akira; Yamazaki, Sunao

2003-03-01

Saccharides including mono- and disaccharides were quantitatively derivatized with 2-aminobenzoic acid (2-AA). These derivatives were then separated by capillary zone electrophoresis with UV detection using 50mM sodium phosphate buffer as the running electrolyte solution. In particular, the saccharide derivatives with the same molecular weight as 2-AA aldohexoses (mannose and glucose) and 2-AA aldopentoses (ribose and xylose) were well separated. The underlying reasons for separation were explored by studying their structural data using 1H and 13C NMR. It was found that the configurational difference between their hydroxyl group at C2 or C3 could cause the difference in Stokes' radii between their molecules and thus lead to different electrophoretic mobilities. The correlation between the electrophoretic behavior of these carbohydrate derivatives and their structures was studied utilizing the calculated molecular models of the 2-AA-labeled mannose, glucose, ribose, and xylose.

Evaporation of iodine-containing off-gas scrubber solution

DOEpatents

Partridge, J.A.; Bosuego, G.P.

1980-07-14

Mercuric nitrate-nitric acid scrub solutions containing radioiodine may be reduced in volume without excessive loss of volatile iodine. The use of concentrated nitric acid during an evaporation process oxidizes the mercury-iodide complex to a less volatile mercuric iodate precipitate.

Radioiodine therapy

MedlinePlus

... 3 days after treatment, you should: Limit your time in public places Not travel by airplane or use public transportation (you may set off the radiation detection machines in airports or at border ... the toilet 2 to 3 times after use For about 5 or more days ...

Sleep duration and sleep quality are associated differently with alterations of glucose homeostasis.

PubMed

Byberg, S; Hansen, A-L S; Christensen, D L; Vistisen, D; Aadahl, M; Linneberg, A; Witte, D R

2012-09-01

Studies suggest that inadequate sleep duration and poor sleep quality increase the risk of impaired glucose regulation and diabetes. However, associations with specific markers of glucose homeostasis are less well explained. The objective of this study was to explore possible associations of sleep duration and sleep quality with markers of glucose homeostasis and glucose tolerance status in a healthy population-based study sample. The study comprised 771 participants from the Danish, population-based cross-sectional 'Health2008' study. Sleep duration and sleep quality were measured by self-report. Markers of glucose homeostasis were derived from a 3-point oral glucose tolerance test and included fasting plasma glucose, 2-h plasma glucose, HbA(1c), two measures of insulin sensitivity (the insulin sensitivity index(0,120) and homeostasis model assessment of insulin sensitivity), the homeostasis model assessment of β-cell function and glucose tolerance status. Associations of sleep duration and sleep quality with markers of glucose homeostasis and tolerance were analysed by multiple linear and logistic regression. A 1-h increment in sleep duration was associated with a 0.3 mmol/mol (0.3%) decrement in HbA(1c) and a 25% reduction in the risk of having impaired glucose regulation. Further, a 1-point increment in sleep quality was associated with a 2% increase in both the insulin sensitivity index(0,120) and homeostasis model assessment of insulin sensitivity, as well as a 1% decrease in homeostasis model assessment of β-cell function. In the present study, shorter sleep duration was mainly associated with later alterations in glucose homeostasis, whereas poorer sleep quality was mainly associated with earlier alterations in glucose homeostasis. Thus, adopting healthy sleep habits may benefit glucose metabolism in healthy populations. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

Periodic Extraction of Interstitial Fluid from the Site of Subcutaneous Insulin Infusion for the Measurement of Glucose: A Novel Single-Port Technique for the Treatment of Type 1 Diabetes Patients

PubMed Central

Lindpointner, Stefan; Korsatko, Stefan; Tutkur, Dina; Bodenlenz, Manfred; Pieber, Thomas R.

2013-01-01

Abstract Background Treatment of type 1 diabetes patients could be simplified if the site of subcutaneous insulin infusion could also be used for the measurement of glucose. This study aimed to assess the agreement between blood glucose concentrations and glucose levels in the interstitial fluid (ISF) that is extracted from the insulin infusion site during periodic short-term interruptions of continuous subcutaneous insulin infusion (CSII). Subjects and Methods A perforated cannula (24 gauge) was inserted into subcutaneous adipose tissue of C-peptide-negative type 1 diabetes subjects (n=13) and used alternately to infuse rapid-acting insulin (100 U/mL) and to extract ISF glucose during a fasting period and after ingestion of a standard oral glucose load (75 g). Results Although periodically interrupted for extracting glucose (every hour for approximately 10 min), insulin infusion with the cannula was adequate to achieve euglycemia during fasting and to restore euglycemia after glucose ingestion. Furthermore, the ISF-derived estimates of plasma glucose levels agreed well with plasma glucose concentrations. Correlation coefficient and median absolute relative difference values were found to be 0.95 and 8.0%, respectively. Error grid analysis showed 99.0% of all ISF glucose values within clinically acceptable Zones A and B (83.5% Zone A, 15.5% Zone B). Conclusions Results show that ISF glucose concentrations measured at the insulin infusion site during periodic short-term interruptions of CSII closely reflect blood glucose levels, thus suggesting that glucose monitoring and insulin delivery may be performed alternately at the same tissue site. A single-port device of this type could be used to simplify and improve glucose management in diabetes. PMID:23126579

Dopamine D2 Receptor Signaling in the Nucleus Accumbens Comprises a Metabolic-Cognitive Brain Interface Regulating Metabolic Components of Glucose Reinforcement.

PubMed

Michaelides, Michael; Miller, Michael L; DiNieri, Jennifer A; Gomez, Juan L; Schwartz, Elizabeth; Egervari, Gabor; Wang, Gene Jack; Mobbs, Charles V; Volkow, Nora D; Hurd, Yasmin L

2017-11-01

Appetitive drive is influenced by coordinated interactions between brain circuits that regulate reinforcement and homeostatic signals that control metabolism. Glucose modulates striatal dopamine (DA) and regulates appetitive drive and reinforcement learning. Striatal DA D2 receptors (D2Rs) also regulate reinforcement learning and are implicated in glucose-related metabolic disorders. Nevertheless, interactions between striatal D2R and peripheral glucose have not been previously described. Here we show that manipulations involving striatal D2R signaling coincide with perseverative and impulsive-like responding for sucrose, a disaccharide consisting of fructose and glucose. Fructose conveys orosensory (ie, taste) reinforcement but does not convey metabolic (ie, nutrient-derived) reinforcement. Glucose however conveys orosensory reinforcement but unlike fructose, it is a major metabolic energy source, underlies sustained reinforcement, and activates striatal circuitry. We found that mice with deletion of dopamine- and cAMP-regulated neuronal phosphoprotein (DARPP-32) exclusively in D2R-expressing cells exhibited preferential D2R changes in the nucleus accumbens (NAc), a striatal region that critically regulates sucrose reinforcement. These changes coincided with perseverative and impulsive-like responding for sucrose pellets and sustained reinforcement learning of glucose-paired flavors. These mice were also characterized by significant glucose intolerance (ie, impaired glucose utilization). Systemic glucose administration significantly attenuated sucrose operant responding and D2R activation or blockade in the NAc bidirectionally modulated blood glucose levels and glucose tolerance. Collectively, these results implicate NAc D2R in regulating both peripheral glucose levels and glucose-dependent reinforcement learning behaviors and highlight the notion that glucose metabolic impairments arising from disrupted NAc D2R signaling are involved in compulsive and perseverative feeding behaviors.

Hypothalamic circuits regulating appetite and energy homeostasis: pathways to obesity

PubMed Central

Timper, Katharina; Brüning, Jens C.

2017-01-01

ABSTRACT The ‘obesity epidemic’ represents a major global socioeconomic burden that urgently calls for a better understanding of the underlying causes of increased weight gain and its associated metabolic comorbidities, such as type 2 diabetes mellitus and cardiovascular diseases. Improving our understanding of the cellular basis of obesity could set the stage for the development of new therapeutic strategies. The CNS plays a pivotal role in the regulation of energy and glucose homeostasis. Distinct neuronal cell populations, particularly within the arcuate nucleus of the hypothalamus, sense the nutrient status of the organism and integrate signals from peripheral hormones including pancreas-derived insulin and adipocyte-derived leptin to regulate calorie intake, glucose metabolism and energy expenditure. The arcuate neurons are tightly connected to other specialized neuronal subpopulations within the hypothalamus, but also to various extrahypothalamic brain regions, allowing a coordinated behavioral response. This At a Glance article gives an overview of the recent knowledge, mainly derived from rodent models, regarding the CNS-dependent regulation of energy and glucose homeostasis, and illustrates how dysregulation of the neuronal networks involved can lead to overnutrition and obesity. The potential impact of recent research findings in the field on therapeutic treatment strategies for human obesity is also discussed. PMID:28592656

Hypothalamic circuits regulating appetite and energy homeostasis: pathways to obesity.

PubMed

Timper, Katharina; Brüning, Jens C

2017-06-01

The 'obesity epidemic' represents a major global socioeconomic burden that urgently calls for a better understanding of the underlying causes of increased weight gain and its associated metabolic comorbidities, such as type 2 diabetes mellitus and cardiovascular diseases. Improving our understanding of the cellular basis of obesity could set the stage for the development of new therapeutic strategies. The CNS plays a pivotal role in the regulation of energy and glucose homeostasis. Distinct neuronal cell populations, particularly within the arcuate nucleus of the hypothalamus, sense the nutrient status of the organism and integrate signals from peripheral hormones including pancreas-derived insulin and adipocyte-derived leptin to regulate calorie intake, glucose metabolism and energy expenditure. The arcuate neurons are tightly connected to other specialized neuronal subpopulations within the hypothalamus, but also to various extrahypothalamic brain regions, allowing a coordinated behavioral response. This At a Glance article gives an overview of the recent knowledge, mainly derived from rodent models, regarding the CNS-dependent regulation of energy and glucose homeostasis, and illustrates how dysregulation of the neuronal networks involved can lead to overnutrition and obesity. The potential impact of recent research findings in the field on therapeutic treatment strategies for human obesity is also discussed. © 2017. Published by The Company of Biologists Ltd.

Pancreatic Endoderm-Derived From Diabetic Patient-Specific Induced Pluripotent Stem Cell Generates Glucose-Responsive Insulin-Secreting Cells.

PubMed

Rajaei, Bahareh; Shamsara, Mehdi; Amirabad, Leila Mohammadi; Massumi, Mohammad; Sanati, Mohammad Hossein

2017-10-01

Human-induced pluripotent stem cells (hiPSCs) can potentially serve as an invaluable source for cell replacement therapy and allow the creation of patient- and disease-specific stem cells without the controversial use of embryos and avoids any immunological incompatibility. The generation of insulin-producing pancreatic β-cells from pluripotent stem cells in vitro provides an unprecedented cell source for personal drug discovery and cell transplantation therapy in diabetes. A new five-step protocol was introduced in this study, effectively induced hiPSCs to differentiate into glucose-responsive insulin-producing cells. This process mimics in vivo pancreatic organogenesis by directing cells through stages resembling definitive endoderm, primitive gut-tube endoderm, posterior foregut, pancreatic endoderm, and endocrine precursor. Each stage of differentiation were characterized by stage-specific markers. The produced cells exhibited many properties of functional β-cells, including expression of critical β-cells transcription factors, the potency to secrete C-peptide in response to high levels of glucose and the presence of mature endocrine secretory granules. This high efficient differentiation protocol, established in this study, yielded 79.18% insulin-secreting cells which were responsive to glucose five times higher than the basal level. These hiPSCs-derived glucose-responsive insulin-secreting cells might provide a promising approach for the treatment of type I diabetes mellitus. J. Cell. Physiol. 232: 2616-2625, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Interruptin B induces brown adipocyte differentiation and glucose consumption in adipose-derived stem cells

PubMed Central

KAEWSUWAN, SIREEWAN; PLUBRUKARN, ANUCHIT; UTSINTONG, MALEERUK; KIM, SEOK-HO; JEONG, JIN-HYUN; CHO, JIN GU; PARK, SANG GYU; SUNG, JONG-HYUK

2016-01-01

Interruptin B has been isolated from Cyclosorus terminans, however, its pharamcological effect has not been fully identified. In the present study, the effects of interruptin B, from C. terminans, on brown adipocyte differentiation and glucose uptake in adipose-derived stem cells (ASCs) were investigated. The results revealed that interruptin B dose-dependently enhanced the adipogenic differentiation of ASCs, with an induction in the mRNA expression levels of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ. In addition, interruptin B efficiently increased the number and the membrane potential of mitochondria and upregulated the mRNA expression levels of uncoupling protein (UCP)-1 and cyclooxygenase (COX)-2, which are all predominantly expressed in brown adipocytes. Interruptin B increased glucose consumption in differentiated ASCs, accompanied by the upregulation in the mRNA expression levels of glucose transporter (GLUT)-1 and GLUT-4. The computational analysis of molecular docking, a luciferase reporter assay and surface plasmon resonance confirmed the marked binding affinity of interruptin B to PPAR-α and PPAR-γ (KD values of 5.32 and 0.10 µM, respectively). To the best of our knowledge, the present study is the first report to show the stimulatory effects of interruptin B on brown adipocyte differentiation and glucose uptake in ASCs, through its role as a dual PPAR-α and PPAR-γ ligand. Therefore, interruptin B could be further developed as a therapeutic agent for the treatment of diabetes. PMID:26781331

Unique regulatory properties of the UDP-glucose:. beta. -1,4-glucan synthetase of Acetobacter xylinum. [Acetobacter xylinum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benziman, M.; Aloni, Y.; Delmer, D.P.

1983-01-01

Conditions have been found for an extremely efficient transfer of glucose from UDP-glucose to a cellulosic ..beta..-1,4-glucan product, using enzyme preparations derived from cells of Acetobacter xylinum. Membrane fractions obtained by rupturing cells in the presence of 20% (w/v) polyethylene glycol-4000 (PEG-4000) exhibited UDP-glucose:..beta..-1,4-glucan synthetase activity 3- to 10-fold higher than those previously reported. Enzyme prepared in this fashion also shows a further marked activation by GTP. The activation (apparent K/sub alpha/ = 35 ..mu..M) is quite specific for GTP. A variety of other nucleotides and nucleotide derivatives had no effect on activity. Guanosine-5'-(lambda-thio)triphosphate, an analog of GTP, is evenmore » more efficient than GTP (K/sub alpha/ = 17 ..mu..M). Enzyme prepared in the absence of PEG-4000 does not respond to GTP because it lacks a protein factor essential for GTP activation. PEG-4000 promotes the interaction of the protein factor with the enzyme. The factor itself is devoid of synthetase activity and does not stimulate activity of the enzyme in the absence of GTP. Under optimal conditions, in the presence of GTP, factor, and PEG-4000, initial rates of enzyme activity that are 200 times higher than those previously reported can be achieved. Such rates exceed 40% of the in vivo rate of cellulose synthesis from glucose. 26 references, 3 figures, 3 tables.« less

Discovery and structure-activity relationships study of thieno[2,3-b]pyridine analogues as hepatic gluconeogenesis inhibitors.

PubMed

Ma, Fei; Liu, Jian; Zhou, Tingting; Lei, Min; Chen, Jing; Wang, Xiachang; Zhang, Yinan; Shen, Xu; Hu, Lihong

2018-05-25

Type 2 diabetes mellitus (T2DM) is a chronic, complex and multifactorial metabolic disorder, and targeting gluconeogenesis inhibition is a promising strategy for anti-diabetic drug discovery. This study discovered a new class of thieno[2,3-b]pyridine derivatives as hepatic gluconeogenesis inhibitors. First, a hit compound (DMT: IC 50  = 33.8 μM) characterized by a thienopyridine core was identified in a cell-based screening of our privileged small molecule library. Structure activity relationships (SARs) study showed that replaced the CF 3 in the thienopyridine core could improve the potency and led to the discovery of 8e (IC 50  = 16.8 μM) and 9d (IC 50  = 12.3 μM) with potent inhibition of hepatic glucose production and good drug-like properties. Furthermore, the mechanism of 8e for the inhibition of hepatic glucose production was also identified, which could be effective through the reductive expression of the mRNA transcription level of gluconeogenic genes, including glucose-6-phosphatase (G6Pase) and hepatic phosphoenolpyruvate carboxykinase (PEPCK). Additionally, 8e could also reduce the fasting blood glucose and improve the oral glucose tolerance and pyruvate tolerance in db/db mice. The optimization of this class of derivatives had provided us a start point to develop new anti-hepatic gluconeogenesis agents. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Effects of sitagliptin or mitiglinide as an add-on to acarbose on daily blood glucose fluctuations measured by 72 h subcutaneous continuous glucose monitoring in Japanese patients with type 2 diabetes: a prospective randomized study.

PubMed

Osonoi, Takeshi; Saito, Miyoko; Tamasawa, Atsuko; Ishida, Hidenori; Osonoi, Yusuke

2014-07-01

Postprandial hyperglycemia and blood glucose fluctuations increase the risk of macroangiopathy in patients with type 2 diabetes mellitus (T2DM). However, few studies have examined the effects of oral hypoglycemic drugs on blood glucose fluctuations in daily life. Twenty-nine T2DM patients treated with acarbose were randomized to receive either sitagliptin (14 patients) or mitiglinide (15 patients) together with acarbose for 4 weeks. Patients were then switched to a combination of 10 mg mitiglinide and 0.2 mg voglibose for 4 weeks. All patients wore a continuous glucose monitoring (CGM) device for 5 - 7 days in week 3 of each treatment period. The percentage of blood glucose levels in the hyperglycemic range, blood glucose indices derived from 24-h CGM profiles and the glycemic parameters (HbA1c, glycated albumin and fasting plasma glucose) were significantly improved by adding sitagliptin or mitiglinide to ongoing acarbose therapy. These parameters also tended to improve in the mitiglinide/voglibose combination period. Daily blood glucose fluctuations were significantly improved by adding sitagliptin or mitiglinide to acarbose, and improved after switching to the mitiglinide/voglibose combination. Larger controlled studies are needed to verify the effects of adding sitagliptin or mitiglinide to acarbose on glucose fluctuations.

Effect of physical training on the oxidation of an oral glucose load at rest: a naturally labeled 13C-glucose study.

PubMed

Krzentowski, G; Pirnay, F; Luyckx, A S; Lacroix, M; Mosora, F; Lefebvre, P J

1983-01-01

This study aimed at investigating, in six healthy, non obese, young (25 +/- 1 years) male volunteers, with strictly normal oral glucose tolerance, the influence of a six week physical training period (60 min bicycling 5 days/week at 30-40% of their individual VO2 max) on the hormonal and metabolic response to a 100 g oral 13C-naturally labeled glucose load given at rest before and 36 h after the last training session. Exogenous glucose oxidation was derived from 13CO2 measurements on expired air. Training resulted in: a 29% increase in VO2 max (2 p less than 0.002), a 27% decrease in plasma triglycerides (2 p less than 0.02). No changes were observed concerning weight, total body K, skinfold tolerance, which was strictly normal before training, remained unchanged, but the insulin response to the oral glucose load decreased by 24% (2 p less than 0.025). Exogenous glucose oxidation was similar before and after training, averaging 35.9 +/- 2.1 and 37.4 +/- 2.0 g/7 h respectively. a 6 week training period, performed on strictly healthy young males, studied at rest, induced an increase in VO2 max, a decrease in plasma triglycerides and a lower insulin response to oral glucose while glucose tolerance and exogenous glucose oxidation remained unchanged.

Murine remote preconditioning increases glucose uptake and suppresses gluconeogenesis in hepatocytes via a brain-liver neurocircuit, leading to counteracting glucose intolerance.

PubMed

Kurabayashi, Atsushi; Tanaka, Chiharu; Matsumoto, Waka; Naganuma, Seiji; Furihata, Mutsuo; Inoue, Keiji; Kakinuma, Yoshihiko

2018-05-01

Our previous study revealed that cyclic hindlimb ischaemia-reperfusion (IR) activates cardiac acetylcholine (ACh) synthesis through the cholinergic nervous system and cell-derived ACh accelerates glucose uptake. However, the mechanisms regulating glucose metabolism in vivo remain unknown. We investigated the effects and mechanisms of IR in mice under pathophysiological conditions. Using IR-subjected male C57BL/6J mice, the effects of IR on blood sugar (BS), glucose uptake, central parasympathetic nervous system (PNS) activity, hepatic gluconeogenic enzyme expression and those of ACh on hepatocellular glucose uptake were assessed. IR decreased BS levels by 20% and increased c-fos immunoreactivity in the center of the PNS (the solitary tract and the dorsal motor vagal nucleus). IR specifically downregulated hepatic gluconeogenic enzyme expression and activities (glucose-6-phosphatase and phosphoenolpyruvate carboxykinase) and accelerated hepatic glucose uptake. Transection of a hepatic vagus nerve branch decreased this uptake and reversed BS decrease. Suppressed gluconeogenic enzyme expression was reversed by intra-cerebroventricular administration of a choline acetyltransferase inhibitor. Moreover, IR significantly attenuated hyperglycaemia in murine model of type I and II diabetes mellitus. IR provides another insight into a therapeutic modality for diabetes mellitus due to regulating gluconeogenesis and glucose-uptake and advocates an adjunctive mode rectifying disturbed glucose metabolism. Copyright © 2018 Elsevier B.V. All rights reserved.

Comparison of labeled acetate and glucose incorporations into lipids in the liver and adipose tissue after intravenous injection in rats.

PubMed

Iritani, Nobuko; Hirakawa, Tomoe; Fukuda, Hitomi; Katsukawa, Michiko; Kouno, Mika

2014-01-01

To compare incorporations of acetate and glucose in tissue total lipids and triacylglycerols (TAG), incorporations of labeled acetate and glucose in livers and epididymal adipose tissues (adipose tissue) were followed after their intravenous injection in the tail vein of individual rat fed a fat-free or 10% corn oil diet. The incorporation of acetate into total lipids (mostly TAG) in the liver reached maximum 2 h after the injection, while the incorporation of glucose decreased more quickly. Incorporation of glucose into total lipids and TAG was more greatly suppressed by dietary corn oil than that of acetate in the liver. In the adipose tissues, the incorporation of labeled acetate or glucose into total lipids was maximum 2-8 h after the injection, while the incorporation of glucose was very low, especially in rats fed the corn oil diet. Moreover, the time courses for labeled acetate and glucose incorporations into total lipids in the liver were parallel to those in plasma, but opposite to those in adipose tissue. TAG synthesized from acetate and glucose in the liver appeared to be mostly transported to adipose tissue. Thus, it is suggested that as the labeled glucose rapidly decreased in the liver, plasma and adipose tissue, TAG should be less derived from dietary carbohydrate than from dietary fat.

Glucose-dependent and Glucose-sensitizing Insulinotropic Effect of Nateglinide: Comparison to Sulfonylureas and Repaglinide

PubMed Central

Wang, Shuya; Dunning, Beth E.

2001-01-01

Nateglinide, a novel D-phenylalanine derivative, stimulates insulin release via closure of KATP channels in pancreatic β-cell, a primary mechanism of action it shares with sulfonylureas (SUs) and repaglinide. This study investigated (1) the influence of ambient glucose levels on the insulinotropic effects of nateglinide, glyburide and repaglinide, and (2) the influence of the antidiabetic agents on glucose-stimulated insulin secretion (GSIS) in vitro from isolated rat islets. The EC50 of nateglinide to stimulate insulin secretion was 14 μM in the presence of 3mM glucose and was reduced by 6-fold in 8mM glucose and by 16-fold in 16mM glucose, indicating a glucose-dependent insulinotropic effect. The actions of glyburide and repaglinide failed to demonstrate such a glucose concentration-dependent sensitization. When tested at fixed and equipotent concentrations (~2x EC50 in the presence of 8mM glucose) nateglinide and repaglinide shifted the EC50s for GSIS to the left by 1.7mM suggesting an enhancement of islet glucose sensitivity, while glimepiride and glyburide caused, respectively, no change and a right shift of the EC50. These data demonstrate that despite a common basic mechanism of action, the insulinotropic effects of different agents can be influenced differentially by ambient glucose and can differentially influence the islet responsiveness to glucose. Further, the present findings suggest that nateglinide may exert a more physiologic effect on insulin secretion than comparator agents and thereby have less propensity to elicit hypoglycemia in vivo. PMID:12369728

Prior exercise alters the difference between arterialised and venous glycaemia: implications for blood sampling procedures.

PubMed

Edinburgh, Robert M; Hengist, Aaron; Smith, Harry A; Betts, James A; Thompson, Dylan; Walhin, Jean-Philippe; Gonzalez, Javier T

2017-05-01

Oral glucose tolerance and insulin sensitivity are common measures, but are determined using various blood sampling methods, employed under many different experimental conditions. This study established whether measures of oral glucose tolerance and oral glucose-derived insulin sensitivity (insulin sensitivity indices; ISI) differ when calculated from venous v. arterialised blood. Critically, we also established whether any differences between sampling methods are consistent across distinct metabolic conditions (after rest v. after exercise). A total of ten healthy men completed two trials in a randomised order, each consisting of a 120-min oral glucose tolerance test (OGTT), either at rest or post-exercise. Blood was sampled simultaneously from a heated hand (arterialised) and an antecubital vein of the contralateral arm (venous). Under both conditions, glucose time-averaged AUC was greater from arterialised compared with venous plasma but importantly, this difference was larger after rest relative to after exercise (0·99 (sd 0·46) v. 0·56 (sd 0·24) mmol/l, respectively; P<0·01). OGTT-derived ISIMatsuda and ISICederholm were lower when calculated from arterialised relative to venous plasma and the arterialised-venous difference was greater after rest v. after exercise (ISIMatsuda: 1·97 (sd 0·81) v. 1·35 (sd 0·57) arbitrary units (au), respectively; ISICederholm : 14·76 (sd 7·83) v. 8·70 (sd 3·95) au, respectively; both P<0·01). Venous blood provides lower postprandial glucose concentrations and higher estimates of insulin sensitivity, compared with arterialised blood. Most importantly, these differences between blood sampling methods are not consistent after rest v. post-exercise, preventing standardised venous-to-arterialised corrections from being readily applied.

Engineering E. coli for simultaneous glucose–xylose utilization during methyl ketone production

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Xi; Goh, Ee-Been; Beller, Harry R.

Previously, we developed an E. coli strain that overproduces medium-chain methyl ketones for potential use as diesel fuel blending agents or as flavors and fragrances. To date, the strain's performance has been optimized during growth with glucose. However, lignocellulosic biomass hydrolysates also contain a substantial portion of hemicellulose-derived xylose, which is typically the second most abundant sugar after glucose. Commercialization of the methyl ketone-producing technology would benefit from the increased efficiency resulting from simultaneous, rather than the native sequential (diauxic), utilization of glucose and xylose. In this study, genetic manipulations were performed to alleviate carbon catabolite repression in our mostmore » efficient methyl ket one-producing strain. A strain engineered for constitutive expression of xylF and xylA (involved in xylose transport and metabolism) showed synchronized glucose and xylose consumption rates. However, this newly acquired capability came at the expense of methyl ketone titer, which decreased fivefold. Further efforts were made to improve methyl ketone production in this strain, and we found that two strategies were effective at enhancing methyl ketone titer: (1) chromosomal deletion of pgi (glucose-6-phosphate isomerase) to increase intracellular NADPH supply and (2) downregulation of CRP (cAMP receptor protein) expression by replacement of the native RBS with an RBS chosen based upon mutant library screening results. Combining these strategies resulted in the most favorable overall phenotypes for simultaneous glucose-xylose consumption without compromising methyl ketone titer at both 1 and 2% total sugar concentrations in shake flasks. This work demonstrated a strategy for engineering simultaneous utilization of C 6 and C 5 sugars in E. coli without sacrificing production of fatty acid-derived compounds.« less

Engineering E. coli for simultaneous glucose–xylose utilization during methyl ketone production

DOE PAGES

Wang, Xi; Goh, Ee-Been; Beller, Harry R.

2018-01-27

Previously, we developed an E. coli strain that overproduces medium-chain methyl ketones for potential use as diesel fuel blending agents or as flavors and fragrances. To date, the strain's performance has been optimized during growth with glucose. However, lignocellulosic biomass hydrolysates also contain a substantial portion of hemicellulose-derived xylose, which is typically the second most abundant sugar after glucose. Commercialization of the methyl ketone-producing technology would benefit from the increased efficiency resulting from simultaneous, rather than the native sequential (diauxic), utilization of glucose and xylose. In this study, genetic manipulations were performed to alleviate carbon catabolite repression in our mostmore » efficient methyl ket one-producing strain. A strain engineered for constitutive expression of xylF and xylA (involved in xylose transport and metabolism) showed synchronized glucose and xylose consumption rates. However, this newly acquired capability came at the expense of methyl ketone titer, which decreased fivefold. Further efforts were made to improve methyl ketone production in this strain, and we found that two strategies were effective at enhancing methyl ketone titer: (1) chromosomal deletion of pgi (glucose-6-phosphate isomerase) to increase intracellular NADPH supply and (2) downregulation of CRP (cAMP receptor protein) expression by replacement of the native RBS with an RBS chosen based upon mutant library screening results. Combining these strategies resulted in the most favorable overall phenotypes for simultaneous glucose-xylose consumption without compromising methyl ketone titer at both 1 and 2% total sugar concentrations in shake flasks. This work demonstrated a strategy for engineering simultaneous utilization of C 6 and C 5 sugars in E. coli without sacrificing production of fatty acid-derived compounds.« less

Early Pregnancy Biochemical Predictors of Gestational Diabetes Mellitus.

PubMed

Powe, Camille E

2017-02-01

Universal oral glucose tolerance-based screening is employed to identify pregnant women with gestational diabetes mellitus (GDM), as treatment of this condition decreases the risk of associated complications. A simple and accurate blood test which identifies women at low or high risk for GDM in the first trimester would have the potential to decrease costs and improve outcomes through prevention or treatment. This review summarizes published data on early pregnancy biomarkers which have been tested as predictors of GDM. A large number of first-trimester biochemical predictors of GDM have been reported, mostly in small case-control studies. These include glycemic markers (fasting glucose, post-load glucose, hemoglobin A1C), inflammatory markers (C-reactive protein, tumor necrosis factor-alpha), insulin resistance markers (fasting insulin, sex hormone-binding globulin), adipocyte-derived markers (adiponectin, leptin), placenta-derived markers (follistatin-like-3, placental growth factor, placental exosomes), and others (e.g., glycosylated fibronectin, soluble (pro)renin receptor, alanine aminotransferase, ferritin). A few large studies suggest that first-trimester fasting glucose or hemoglobin A1C may be useful for identifying women who would benefit from early GDM treatment. To translate the findings from observational studies of first-trimester biomarkers for GDM to clinical practice, trials or cost-effectiveness analyses of screening and treatment strategies based on these novel biomarkers are needed.

Biotransformation of pineapple juice sugars into dietetic derivatives by using a cell free oxidoreductase from Zymomonas mobilis together with commercial invertase.

PubMed

Aziz, M G; Michlmayr, H; Kulbe, K D; Del Hierro, A M

2011-01-05

An easy procedure for cell free biotransformation of pineapple juice sugars into dietetic derivatives was accomplished using a commercial invertase and an oxidoreductase from Zymomonas mobilis. First, pineapple juice sucrose was quantitatively converted into glucose and fructose by invertase, thus increasing the concentration of each monosaccharide in the original juice to almost twice. In a second step, glucose-fructose oxidoreductase (GFOR) transformed glucose into gluconolactone, and fructose into the low calorie sweetener sorbitol. The advantage of using GFOR is simultaneous reduction of fructose and oxidation of glucose, allowing the continuous regeneration of the essential coenzyme NADP(H), that is tightly bound to the enzyme. The yield of GFOR catalyzed sugar conversion depends on initial pH and control of pH during the reaction. At optimal conditions (pH control at 6.2) a maximum of 80% (w/v) sugar conversion was obtained. Without pH control, GFOR is inactivated rapidly due to gluconic acid formation. Therefore, conversion yields are relatively low at the natural pH of pineapple juice. The application of this process might be more advantageous on juices of other tropical fruits (papaya, jackfruit, mango) due to their naturally given higher pH. Copyright © 2010 Elsevier Inc. All rights reserved.

Chitosan-assisted differentiation of porcine adipose tissue-derived stem cells into glucose-responsive insulin-secreting clusters

PubMed Central

Lin, Yuan-Yu; Chen, Yu-Jen; Liu, Bing-Hsien; Wong, Shiu-Chung; Wu, Cheng-Yu; Chang, Yun-Tsui; Chou, Han-Yi E.

2017-01-01

The unique advantage of easy access and abundance make the adipose-derived stem cells (ADSCs) a promising system of multipotent cells for transplantation and regenerative medicine. Among the available sources, porcine ADSCs (pADSCs) deserve especial attention due to the close resemblance of human and porcine physiology, as well as for the upcoming availability of humanized porcine models. Here, we report on the isolation and conversion of pADSCs into glucose-responsive insulin-secreting cells. We used the stromal-vascular fraction of the dorsal subcutaneous adipose from 9-day-old male piglets to isolate pADSCs, and subjected the cells to an induction scheme for differentiation on chitosan-coated plates. This one-step procedure promoted differentiation of pADSCs into pancreatic islet-like clusters (PILC) that are characterized by the expression of a repertoire of pancreatic proteins, including pancreatic and duodenal homeobox (Pdx-1), insulin gene enhancer protein (ISL-1) and insulin. Upon glucose challenge, these PILC secreted high amounts of insulin in a dose-dependent manner. Our data also suggest that chitosan plays roles not only to enhance the differentiation potential of pADSCs, but also to increase the glucose responsiveness of PILCs. Our novel approach is, therefore, of great potential for transplantation-based amelioration of type 1 diabetes. PMID:28253305

Ethanol production by Saccharomyces cerevisiae using lignocellulosic hydrolysate from Chrysanthemum waste degradation.

PubMed

Quevedo-Hidalgo, Balkys; Monsalve-Marín, Felipe; Narváez-Rincón, Paulo César; Pedroza-Rodríguez, Aura Marina; Velásquez-Lozano, Mario Enrique

2013-03-01

Ethanol production derived from Saccharomyces cerevisiae fermentation of a hydrolysate from floriculture waste degradation was studied. The hydrolysate was produced from Chrysanthemum (Dendranthema grandiflora) waste degradation by Pleurotus ostreatus and characterized to determine the presence of compounds that may inhibit fermentation. The products of hydrolysis confirmed by HPLC were cellobiose, glucose, xylose and mannose. The hydrolysate was fermented by S. cerevisiae, and concentrations of biomass, ethanol, and glucose were determined as a function of time. Results were compared to YGC modified medium (yeast extract, glucose and chloramphenicol) fermentation. Ethanol yield was 0.45 g g(-1), 88 % of the maximal theoretical value. Crysanthemum waste hydrolysate was suitable for ethanol production, containing glucose and mannose with adequate nutrients for S. cerevisiae fermentation and low fermentation inhibitor levels.

Hyper-G stress-induced hyperglycemia in rats mediated by glucoregulatory hormones

NASA Technical Reports Server (NTRS)

Daligcon, B. C.; Oyama, J.

1985-01-01

The present investigation is concerned with possible relations of the hyperglycemic response of rats exposed to hyper-G stress to (1) alterations in blood levels of the glucoregulatory hormones and gluconeogenic substrates, and (2) changes in insulin response on muscle glucose uptake. Male Sprague-Dawley rats weighing 250-300 g were used in the study. The results of the experiments indicate that the initial rapid rise in blood glucose of rats exposed to hyper-G stress is mediated by increases in circulating catecholamines and glucagon, both potent stimulators of hepatic gluconeogenesis. Lactate, derived from epinephrine stimulation of muscle glycogenolysis, appears to be a major precursor for the initial rise in blood glucose. The inhibition of the insulin-stimulated glucose uptake by muscle tissues may be a factor in the observed sustained hyperglycemia.

Higher transport and metabolism of glucose in astrocytes compared with neurons: a multiphoton study of hippocampal and cerebellar tissue slices.

PubMed

Jakoby, Patrick; Schmidt, Elke; Ruminot, Iván; Gutiérrez, Robin; Barros, L Felipe; Deitmer, Joachim W

2014-01-01

Glucose is the most important energy substrate for the brain, and its cellular distribution is a subject of great current interest. We have employed fluorescent glucose probes, the 2-deoxy-D-glucose derivates 6- and 2-([N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose) (2-NBDG), to measure transport and metabolism of glucose in acute slices of mouse hippocampus and cerebellum. In the hippocampus, 6-NBDG, which is not metabolized and hence indicates glucose transport, was taken up faster in astrocyte-rich layers (Stratum radiatum [S.r.], Stratum oriens [S.o.]) than in pyramidal cells. Metabolizable 2-NBDG showed larger signals in S.r. and S.o. than in Stratum pyramidale, suggesting faster glucose utilization rate in the astrocyte versus the neuronal compartment. Similarly, we found higher uptake and temperature-sensitive metabolism of 2-NBDG in Bergmann glia when compared with adjacent Purkinje neurons of cerebellar slices. A comparison between 6-NBDG transport and glucose transport in cultured cells using a fluorescence resonance energy transfer nanosensor showed that relative to glucose, 6-NBDG is transported better by neurons than by astrocytes. These results indicate that the preferential transport and metabolism of glucose by glial cells versus neurons proposed for the hippocampus and cerebellum by ourselves (in vitro) and for the barrel cortex by Chuquet et al. (in vivo) is more pronounced than anticipated.

Fructose utilization during exercise in men: rapid conversion of ingested fructose to circulating glucose.

PubMed

Jandrain, B J; Pallikarakis, N; Normand, S; Pirnay, F; Lacroix, M; Mosora, F; Pachiaudi, C; Gautier, J F; Scheen, A J; Riou, J P

1993-05-01

The aim of the present study was to compare the metabolic fate of repeated doses of fructose or glucose ingested every 30 min during long-duration moderate-intensity exercise in men. Healthy volunteers exercised for 3 h on a treadmill at 45% of their maximal oxygen consumption rate. "Naturally labeled" [13C]glucose or [13C]fructose was given orally at 25-g doses every 30 min (total feeding: 150 g; n = 6 in each group). Substrate utilization was evaluated by indirect calorimetry, and exogenous sugar oxidation was measured by isotope ratio mass spectrometry on expired CO2. Results were corrected for baseline drift in 13C/12C ratio in expired air due to exercise alone. Fructose conversion to plasma glucose was measured combining gas chromatography and isotope ratio mass spectrometry. Most of the ingested glucose was oxidized: 81 +/- 4 vs. 57 +/- 2 g/3 h for fructose (2P < 0.005). Exogenous glucose covered 20.8 +/- 1.4% of the total energy need (+/- 6.7 MJ) compared with 14.0 +/- 0.6% for fructose (2P < 0.005). The contribution of total carbohydrates was significantly higher and that of lipids significantly lower with glucose than with fructose. The blood glucose response was similar in both protocols. From 90 to 180 min, 55-60% of circulating glucose was derived from ingested fructose. In conclusion, when ingested repeatedly during moderate-intensity prolonged exercise, fructose is metabolically less available than glucose, despite a high rate of conversion to circulating glucose.

Glucose concentrations modulate brain-derived neurotrophic factor responsiveness of neurones in the paraventricular nucleus of the hypothalamus.

PubMed

McIsaac, W; Ferguson, A V

2017-04-01

The hypothalamic paraventricular nucleus (PVN) is critical for normal energy balance and has been shown to contain high levels of both brain-derived neurotrophic factor (BDNF) and tropomyosin-receptor kinase B mRNA. Microinjections of BDNF into the PVN increase energy expenditure, suggesting that BDNF plays an important role in energy homeostasis through direct actions in this nucleus. The present study aimed to examine the postsynaptic effects of BDNF on the membrane potential of PVN neurones, and also to determine whether extracellular glucose concentrations modulated these effects. We used hypothalamic PVN slices from male Sprague-Dawley rats to perform whole cell current-clamp recordings from PVN neurones. BDNF was bath applied at a concentration of 2 nmol L -1 and the effects on membrane potential determined. BDNF caused depolarisations in 54% of neurones (n=25; mean±SEM, 8.9±1.2 mV) and hyperpolarisations in 23% (n=11; -6.7±1.4 mV), whereas the remaining cells were unaffected. These effects were maintained in the presence of tetrodotoxin (n=9; 56% depolarised, 22% hyperpolarised, 22% nonresponders), or the GABA a antagonist bicuculline (n=12; 42% depolarised, 17% hyperpolarised, 41% nonresponders), supporting the conclusion that these effects on membrane potential were postsynaptic. Current-clamp recordings from PVN neurones next examined the effects of BDNF on these neurones at varying extracellular glucose concentrations. Larger proportions of PVN neurones hyperpolarised in response to BDNF as the glucose concentrations decreased [10 mmol L -1 glucose 23% (n=11) of neurones hyperpolarised, whereas, at 0.2 mmol L -1 glucose, 71% showed hyperpolarising effects (n=12)]. Our findings reveal that BDNF has direct GABA A independent effects on PVN neurones, which are modulated by local glucose concentrations. The latter observation further emphasises the critical importance of using physiologically relevant conditions in an investigation of the central pathways involved in the regulation of energy homeostasis. © 2017 British Society for Neuroendocrinology.

High glucose alters the expression of genes involved in proliferation and cell-fate specification of embryonic neural stem cells.

PubMed

Fu, J; Tay, S S W; Ling, E A; Dheen, S T

2006-05-01

Maternal diabetes induces neural tube defects during embryogenesis. Since the neural tube is derived from neural stem cells (NSCs), it is hypothesised that in diabetic pregnancy neural tube defects result from altered expression of developmental control genes, leading to abnormal proliferation and cell-fate choice of NSCs. Cell viability, proliferation index and apoptosis of NSCs and differentiated cells from mice exposed to physiological or high glucose concentration medium were examined by a tetrazolium salt assay, 5-bromo-2'-deoxyuridine incorporation, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling and immunocytochemistry. Expression of developmental genes, including sonic hedgehog (Shh), bone morphogenetic protein 4 (Bmp4), neurogenin 1/2 (Neurog1/2), achaete-scute complex-like 1 (Ascl1), oligodendrocyte transcription factor 1 (Olig1), oligodendrocyte lineage transcription factor 2 (Olig2), hairy and enhancer of split 1/5 (Hes1/5) and delta-like 1 (Dll1), was analysed by real-time RT-PCR. Proliferation index and neuronal specification in the forebrain of embryos at embryonic day 11.5 were examined histologically. High glucose decreased the proliferation of NSCs and differentiated cells. The incidence of apoptosis was increased in NSCs treated with high glucose, but not in the differentiated cells. High glucose also accelerated neuronal and glial differentiation from NSCs. The decreased proliferation index and early differentiation of neurons were evident in the telencephalon of embryos derived from diabetic mice. Exposure to high glucose altered the mRNA expression levels of Shh, Bmp4, Neurog1/2, Ascl1, Hes1, Dll1 and Olig1 in NSCs and Shh, Dll1, Neurog1/2 and Hes5 in differentiated cells. The changes in proliferation and differentiation of NSCs exposed to high glucose are associated with altered expression of genes that are involved in cell-cycle progression and cell-fate specification during neurulation. These changes may form the basis for the defective neural tube patterning observed in embryos of diabetic pregnancies.

Insights into Supramolecular Sites Responsible for Complete Separation of Biomass-Derived Phenolics and Glucose in Metal-Organic Framework NU-1000.

PubMed

Yabushita, Mizuho; Li, Peng; Durkin, Kathleen A; Kobayashi, Hirokazu; Fukuoka, Atsushi; Farha, Omar K; Katz, Alexander

2017-05-02

The molecular origins of adsorption of lignin-derived phenolics to metal-organic framework NU-1000 are investigated from aqueous solution as well as in competitive mode with glucose present in the same aqueous mixture. A comparison of adsorption equilibrium constants (K ads ) for phenolics functionalized with either carboxylic acid or aldehyde substituents demonstrated only a slight increase (less than a factor of 6) for the former according to both experiments and calculations. This small difference in K ads between aldehyde and carboxylic-acid substituted adsorbates is consistent with the pyrene unit of NU-1000 as the adsorption site, rather than the zirconia nodes, while at saturation coverage, the adsorption capacity suggests multiple guests per pyrene. Experimental standard free energies of adsorption directly correlated with the molecular size and electronic structure calculations confirmed this direct relationship, with the pyrene units as adsorption site. The underlying origins of this relationship are grounded in noncovalent π-π interactions as being responsible for adsorption, the same interactions present in the condensed phase of the phenolics, which to a large extent govern their heat of vaporization. Thus, NU-1000 acts as a preformed aromatic cavity for driving aromatic guest adsorption from aqueous solution and does so specifically without causing detectable glucose adsorption from aqueous solution, thereby achieving complete glucose-phenolics separations. The reusability of NU-1000 during an adsorption/desorption cycle was good, even with some of the phenolic compounds with greatest affinity not easiliy removed with water and ethanol washes at room temperature. A competitive adsorption experiment gave an upper bound for K ads for glucose of at most 0.18 M -1 , which can be compared with K ads for the phenolics investigated here, which fell in the range of 443-42 639 M -1 . The actual value of K ads for glucose may be much closer to zero given the lack of observed glucose uptake with NU-1000 as adsorbent.

High Glucose-Induced Reactive Oxygen Species Stimulates Human Mesenchymal Stem Cell Migration Through Snail and EZH2-Dependent E-Cadherin Repression.

PubMed

Oh, Ji Young; Choi, Gee Euhn; Lee, Hyun Jik; Jung, Young Hyun; Ko, So Hee; Chae, Chang Woo; Kim, Jun Sung; Kim, Seo Yihl; Lim, Jae Ryong; Lee, Chang-Kyu; Han, Ho Jae

2018-01-01

Glucose plays an important role in stem cell fate determination and behaviors. However, it is still not known how glucose contributes to the precise molecular mechanisms responsible for stem cell migration. Thus, we investigate the effect of glucose on the regulation of the human umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC) migration, and analyze the mechanism accompanied by this effect. Western blot analysis, wound healing migration assays, immunoprecipitation, and chromatin immunoprecipitation assay were performed to investigate the effect of high glucose on hUCB-MSC migration. Additionally, hUCB-MSC transplantation was performed in the mouse excisional wound splinting model. High concentration glucose (25 mM) elicits hUCB-MSC migration compared to normal glucose and high glucose-pretreated hUCB-MSC transplantation into the wound sites in mice also accelerates skin wound repair. We therefore elucidated the detailed mechanisms how high glucose induces hUCB-MSC migration. We showed that high glucose regulates E-cadherin repression through increased Snail and EZH2 expressions. And, we found high glucose-induced reactive oxygen species (ROS) promotes two signaling; JNK which regulates γ-secretase leading to the cleavage of Notch proteins and PI3K/Akt signaling which enhances GSK-3β phosphorylation. High glucose-mediated JNK/Notch pathway regulates the expression of EZH2, and PI3K/Akt/GSK-3β pathway stimulates Snail stabilization, respectively. High glucose enhances the formation of EZH2/Snail/HDAC1 complex in the nucleus, which in turn causes E-cadherin repression. This study reveals that high glucose-induced ROS stimulates the migration of hUCB-MSC through E-cadherin repression via Snail and EZH2 signaling pathways. © 2018 The Author(s). Published by S. Karger AG, Basel.

Imaging agent and method of use

DOEpatents

Wieland, Donald M.; Brown, Lawrence E.; Beierwaltes, William H.; Wu, Jiann-long

1986-04-22

A new radiopharmaceutical composition for use in nuclear medicine comprises a radioiodinated meta-iodobenzylguanidine. The composition is used as an imaging agent for the heart, adrenal medulla, and tumors of the adrenal medulla and can be used for treatment of tumors of the adrenal medulla.

Intestinal transit of a glucose bolus and incretin kinetics: a mathematical model with application to the oral glucose tolerance test.

PubMed

Salinari, Serenella; Bertuzzi, Alessandro; Mingrone, Geltrude

2011-06-01

The rate of appearance (R(a)) of exogenous glucose in plasma after glucose ingestion is presently measured by tracer techniques that cannot be used in standard clinical testing such as the oral glucose tolerance test (OGTT). We propose a mathematical model that represents in a simple way the gastric emptying, the transport of glucose along the intestinal tract, and its absorption from gut lumen into portal blood. The model gives the R(a) time course in terms of parameters with a physiological counterpart and provides an expression for the release of incretin hormones as related to glucose transit into gut lumen. Glucose absorption was represented by assuming two components related to a proximal and a distal transporter. Model performance was evaluated by numerical simulations. The model was then validated by fitting OGTT glucose and GLP-1 data in healthy controls and type 2 diabetic patients, and useful information was obtained for the rate of gastric emptying, the rate of glucose absorption, the R(a) profile, the insulin sensitivity, and the glucose effectiveness. Model-derived estimates of insulin sensitivity were well correlated (r = 0.929 in controls and 0.886 in diabetic patients) to data obtained from the euglycemic hyperinsulinemic clamp. Although the proposed OGTT analysis requires the measurement of an additional hormone concentration (GLP-1), it appears to be a reasonable choice since it avoids complex and expensive techniques, such as isotopes for glucose R(a) measurement and direct assessment of gastric emptying and intestinal transit, and gives additional correlated information, thus largely compensating for the extra expense.

The limit of detection in scintigraphic imaging with I-131 in patients with differentiated thyroid carcinoma

NASA Astrophysics Data System (ADS)

Hänscheid, H.; Lassmann, M.; Buck, A. K.; Reiners, C.; Verburg, F. A.

2014-05-01

Radioiodine scintigraphy influences staging and treatment in patients with differentiated thyroid carcinoma. The limit of detection for fractional uptake in an iodine avid focus in a scintigraphic image was determined from the number of lesion net counts and the count density of the tissue background. The count statistics were used to calculate the diagnostic activity required to elevate the signal from a lesion with a given uptake significantly above a homogeneous background with randomly distributed counts per area. The dependences of the minimal uptake and the minimal size of lesions visible in a scan on several parameters of influence were determined by linking the typical biokinetics observed in iodine avid tissue to the lesion mass and to the absorbed dose received in a radioiodine therapy. The detection limits for fractional uptake in a neck lesion of a typical patient are about 0.001% after therapy with 7000 MBq, 0.01% for activities typically administered in diagnostic assessments (74-185 MBq), and 0.1% after the administration of 10 MBq I-131. Lesions at the limit of detection in a diagnostic scan with biokinetics eligible for radioiodine therapy are small with diameters of a few millimeters. Increasing the diagnostic activity by a factor of 4 reduces the diameter of visible lesions by 25% or about 1 mm. Several other determinants have a comparable or higher influence on the limit of detection than the administered activity; most important are the biokinetics in both blood pool and target tissue and the time of measurement. A generally valid recommendation for the timing of the scan is impossible as the time of the highest probability to detect iodine avid tissue depends on the administered activity as well as on the biokinetics in the lesion and background in the individual patient.

Clinical experience with recombinant human thyroid-stimulating hormone (rhTSH): whole-body scanning with iodine-131.

PubMed

Reiners, C; Luster, M; Lassmann, M

1999-01-01

Whole-body scanning (WBS) with iodine-131 (I-131) is currently used together with serum thyroglobulin (Tg) measurement in the diagnostic follow-up of well-differentiated thyroid carcinoma. One of the main disadvantages of I-131 WBS is its requirement of repeated weeks-long withdrawal of thyroid hormone suppression therapy (THST) to raise endogenous thyroid-stimulating hormone (TSH) production. This results in hypothyroidism and associated abnormalities, discomfort and morbidity. Recently, however, a series of multicentre clinical studies established the efficacy, safety, non-antigenicity, and quality of life benefits of recombinant human TSH (rhTSH, Thyrogen, thyrotropin alfa, Genzyme Corporation, Cambridge, MA, USA) in promoting radioiodine uptake and permitting sensitive I-131 WBS in patients on THST after initial therapy of well-differentiated thyroid cancer. Thus in everyday practice, rhTSH administration may in many cases supersede THST withdrawal as a preparative method for I-131 imaging. With the use of rhTSH, as whenever I-131 WBS is performed, useful and accurate imaging requires meticulous attention to good scanning practices. These include use of appropriate equipment, proper timing, sufficient scanning time, vigilance against artifacts and iodine contamination, and consideration of additional imaging in the case of ambiguous 48-hour scans. Whole-body retention of I-131 is approximately 50% greater during hypothyroidism after THST withdrawal than during euthyroidism on THST and rhTSH. Therefore, it is important to use an adequate diagnostic activity of > or =4 mCi (148 MBq) to compensate for the faster radioiodine clearance in the euthyroid state permitted by rhTSH administration. Ongoing dosimetric research eventually may provide more specific guidance regarding radioiodine activities for diagnostic, and, particularly, therapeutic purposes, with the use of rhTSH.

Outpatient radioiodine therapy for thyroid cancer: a safe nuclear medicine procedure.

PubMed

Willegaignon, José; Sapienza, Marcelo; Ono, Carla; Watanabe, Tomoco; Guimarães, Maria Inês; Gutterres, Ricardo; Marechal, Maria Helena; Buchpiguel, Carlos

2011-06-01

To evaluate the dosimetric effect of outpatient radioiodine therapy for thyroid cancer in members of a patient's family and their living environment, when using iodine-131 doses reaching 7.4 GBq. The following parameters were thus defined: (a) whole-body radiation doses to caregivers, (b) the production of contaminated solid waste, and (c) radiation potential and surface contamination within patients' living quarters. In total, 100 patients were treated on an outpatient basis, taking into consideration their acceptable living conditions, interests, and willingness to comply with medical and radiation safety guidelines. Both the caregivers and the radiation dose potentiality inside patients' residences were monitored by using thermoluminescent dosimeters. Surface contamination and contaminated solid wastes were identified and measured with a Geiger-Müller detector. A total of 90 monitored individuals received a mean dose of 0.27 (±0.28) mSv, and the maximum dose registered was 1.6 mSv. The mean value for the potential dose within all living quarters was 0.31 (±0.34) mSv, and the mean value per monitored surface was 5.58 Bq/cm(2) for all the 1659 points measured. The overall production of contaminated solid wastes was at a low level, being about 3 times less than the exemption level indicated by the International Atomic Energy Agency. This study indicates that the treatment of thyroid cancer by applying radioiodine activities up to 7.4 GBq, on an outpatient basis, is a safe procedure, especially when supervised by qualified professionals. This alternative therapy should be a topic for careful discussion considering the high potential for reducing costs in healthcare and improving patient acceptance.

Trends in Costs of Thyroid Disease Treatment in Denmark during 1995-2015.

PubMed

Møllehave, Line Tang; Linneberg, Allan; Skaaby, Tea; Knudsen, Nils; Ehlers, Lars; Jørgensen, Torben; Thuesen, Betina Heinsbæk

2018-03-01

Iodine fortification (IF) may contribute to changes in costs of thyroid disease treatment through changes in disease patterns. From a health economic perspective, assessment of the development in costs of thyroid disease treatment in the population is pertinent. To assess the trends in annual medicine and hospital costs of thyroid disease treatment during 1995-2015 in Denmark, i.e., before and after the introduction of mandatory IF in 2000. Information on treatments for thyroid disease (antithyroid medication, thyroid hormone therapy, thyroid surgery, and radioiodine treatment) was obtained from nationwide registers. Costs were valued at 2015 prices using sales prices for medicines and the Danish Diagnosis-Related Group (DRG) and Danish Ambulatory Grouping System (DAGS) tariffs of surgeries/radioiodine treatments. Results were adjusted for changes in population size and age and sex distribution. The total direct medicine and hospital costs of thyroid disease treatment increased from EUR ∼190,000 per 100,000 persons in 1995 to EUR ∼270,000 per 100,000 persons in 2015. This was mainly due to linearly increased costs of thyroid hormone therapy and increased costs of thyroid surgery since 2008. Costs of antithyroid medication increased slightly and transiently after IF, while costs of radioiodine treatment remained constant. Costs of thyroid hormone therapy and thyroid surgery did not follow the development in the prevalence of hypothyroidism and structural thyroid diseases observed in concurrent studies. The costs of total direct medicine and hospital costs for thyroid disease treatment in Denmark increased from 1995 to 2015. This is possibly due to several factors, e.g., changes in treatment practices, and the direct effect of IF alone remains to be estimated.

Radioiodinated cholesteryl ester analogs as residualizing tracers of lipoproteins disposition

DOE Office of Scientific and Technical Information (OSTI.GOV)

DeForge, L.E.

1989-01-01

Due to the importance of low density lipoprotein (LDL) in lipid metabolism and atherosclerosis, efforts were made to incorporate {sup 125}I-cholesteryl iopanoate ({sup 125}I-CI), a residualizing cholesteryl ester (CE) analog, into the lipid core of LDL. This preparation is potentially useful as a scintigraphically detectable tracer of LDL uptake into atheroma and tissues such as the adrenal and liver. Initial studies using a cholesterol-fed rabbit model of atherosclerosis validated the use of {sup 125}I-CI as a tracer of CE deposition. However, scintigraphy revealed considerable nonspecific {sup 125}I-CI uptake due to tissue cholesterol loading. An alternative animal model was the guineamore » pig, which responds moderately to cholesterol feeding and carries the plasma cholesterol predominantly as LDL. Dietary fat and cholesterol, coupled with chronic aortic injury caused by an indwelling catheter, resulted in lipid containing, smooth muscle cell proliferative lesions in many animals. However, further studies are necessary to fully characterize this model. In additional studies, in vitro methods for incorporating {sup 125}I-CI into LDL were examined. These included a reconstitution procedure described by Krieger et al. and a procedure involving incubation of detergent (Tween 20)-solubilized {sup 125}I-CI with plasma. Although both LDL preparations were taken up normally by cultured fibroblasts, the plasma clearance rate of reconstituted LDL was markedly abnormal in guinea pigs. In contrast, LDL labeled by the detergent method cleared from the plasma identically to a radioiodinated LDL control. Therefore, this latter procedure was also used to incorporate two novel radioiodinated cholesteryl ether analogs {sup 125}I-CI cholesteryl m-iodobenzyl ether ({sup 125}I-CIDE) and {sup 125}I-cholesteryl 12-(miodophenyl)dodecyl ether ({sup 125}I-CIDE) into LDL.« less

An audit of management of differentiated thyroid cancer in specialist and non-specialist clinic settings.

PubMed

Kumar, H; Daykin, J; Holder, R; Watkinson, J C; Sheppard, M C; Franklyn, J A

2001-06-01

Thyroid cancer is the most common endocrine malignancy but is none the less rare. Some aspects of its management remain controversial. Previous audits of patient management in the United Kingdom have revealed deficiencies, especially in communication between specialists. We have audited patient management in a large university-associated teaching hospital, assessing points of good practice identified from published guidelines and reviews, and have compared findings in groups of patients managed jointly by specialists with an interest in thyroid cancer (including surgeon, endocrinologist and oncologist) with a group managed by other clinicians outside that setting. Retrospective case-note review of 205 patients with differentiated (papillary or follicular) cancer including group A (n = 134; managed in a specialist multi-disciplinary clinic setting) and group B (n = 71; managed in other clinic settings). Points of good practice investigated were adequacy of surgery, surgical complications, prescription and adequacy of T4 treatment, adequacy of monitoring by measurement of serum thyroglobulin and action taken and appropriate administration of ablative radioiodine. Deficiencies in management of the cohort as a whole were identified, including inadequate surgery and inadequate TSH suppression in approximately one-fifth of the cases. Monitoring with thyroglobulin measurements and action when serum thyroglobulin was high were also inadequate in some cases and ablative radioiodine was not given, despite being indicated in 11.7% of the cohort. Inadequate surgery and failure to administer radioiodine were less common in those managed in a specialist clinic setting than in those managed in other clinic settings. The findings highlight the need for locally agreed protocols in managing relatively rare endocrine disorders such as thyroid cancer and argue in favour of centralization of expertise and patient management in multi-disciplinary specialist clinic settings.

Mutant protein of recombinant human granulocyte colony-stimulating factor for receptor binding assay.

PubMed

Watanabe, M; Fukamachi, H; Uzumaki, H; Kabaya, K; Tsumura, H; Ishikawa, M; Matsuki, S; Kusaka, M

1991-05-15

A new mutant protein of recombinant human granulocyte colony-stimulating factor (rhG-CSF) was produced for the studies on receptors for human G-CSF. The mutant protein [(Tyr1, Tyr3]rhG-CSF), the biological activity of which was almost equal to that of rhG-CSF, was prepared by the replacement of threonine-1 and leucine-3 of rhG-CSF with tyrosine. The radioiodinated preparation of the mutant protein showed high specific radioactivity and retained full biological activity for at least 3 weeks. The binding capacity of the radioiodinated ligand was compared with that of [35S]rhG-CSF. Both radiolabeled ligands showed specific binding to murine bone marrow cells. Unlabeled rhG-CSF and human G-CSF purified from the culture supernatant of the human bladder carcinoma cell line 5637 equally competed for the binding of labeled rhG-CSFs in a dose-dependent manner, demonstrating that the sugar moiety of human G-CSF made no contribution to the binding of human G-CSF to target cells. In contrast, all other colony-stimulating factors and lymphokines examined did not affect the binding. Scatchard analysis of the specific binding of both labeled ligands revealed a single class of binding site with an apparent dissociation constant (Kd) of 20-30 pM and 100-200 maximal binding sites per cell. These data indicate that the radioiodinated preparation of the mutant protein binds the same specific receptor with the same affinity as [35S]rhG-CSF. The labeled mutant protein also showed specific binding to human circulating neutrophils.(ABSTRACT TRUNCATED AT 250 WORDS)

Results of preventive radioiodine therapy in euthyroid patients with history of hyperthyroidism prior to administration of amiodarone with permanent atrial fibrillation--a preliminary study.

PubMed

Czarnywojtek, Agata; Zgorzalewicz-Stachowiak, Małgorzata; Woliński, Kosma; Płazińska, Maria Teresa; Miechowicz, Izabela; Kwiecińska, Barbara; Czepczyński, Rafał; Królicki, Leszek; Ruchała, Marek

2014-01-01

Radioiodine (RAI) therapy is a standard procedure in the treatment of hyperthyroidism. However, the use of RAI in euthyroid patients requiring chronic administration of amiodarone (AM) where other antiarrhythmic drugs may lack efficacy is still controversial. The aim of this study was to assess the safety and efficacy of an AM therapy prior to treatment with radioiodine therapy in euthyroid patients with permanent atrial fibrillation (PAF), who had been treated for hyperthyroidism in the past. This was a retrospective observational study. Patients were assessed at baseline and two, six, eight, and 12 months after RAI therapy. 17 euthyroid patients with PAF were qualified to the RAI (female/male 3/14; age range 65 to 87, median 71). The patients required chronic administration of AM as a prophylaxis against sudden death. Each patient received an ablative dose of 800 MBq (22 mCi) of 131I. At baseline and during follow-up, no side effects of the therapy and no signs of drug intolerance were observed. Subclinical hyperthyroidism occurred in two (11.8%) cases after two months of RAI and five weeks of AM administration. In this situation, RAI therapy was repeated. Three patients (17.6%) after six months, and another two (11.8%) after eight months, required an additional dose of 131I due to amiodarone-induced thyrotoxicosis (AIT). Twelve patients (70.6%) returned to spontaneous sinus rhythm within two months. Fourteen patients (82.4%) had sinus rhythm during follow-up after six and 12 months of treatment. Preventive RAI in euthyroid (but previously hyperthyroid) patients with PAF before administration of AM may be the method of choice. This is particularly important for patients who will require permanent AM administration as a life-saving drug.

Laser ablation and 131-iodine: a 24-month pilot study of combined treatment for large toxic nodular goiter.

PubMed

Chianelli, M; Bizzarri, G; Todino, V; Misischi, I; Bianchini, A; Graziano, F; Guglielmi, R; Pacella, C M; Gharib, H; Papini, E

2014-07-01

It is normally recognized that the preferred treatment in large toxic thyroid nodules should be thyroidectomy. The aim of the study was to assess the efficacy of combined laser ablation treatment (LAT) and radioiodine 131 (131I) treatment of large thyroid toxic nodules with respect to rapidity of control of local symptoms, of hyperthyroidism, and of reduction of administered 131I activity in patients at refusal or with contraindications to surgery. We conducted a pilot study at a single center specializing in thyroid care. Fifteen patients were treated with LAT, followed by 131I (group A), and a series of matched consecutive patients were treated by 131I only (group B). Laser energy was delivered with an output power of 3 W (1800 J per fiber per treatment) through two 75-mm, 21-gauge spinal needles. Radioiodine activity was calculated to deliver 200 Gy to the hyperfunctioning nodule. Thyroid function, thyroid peroxidase antibody, thyroglobulin antibody, ultrasound, and local symptoms were measured at baseline and up to 24 months. Nodule volume reduction at 24 months was: 71.3 ± 13.4 vs 47.4 ± 5.5%, group A (LAT+131I) vs group B (131I), respectively; P < .001). In group A (LAT+131I), a reduction in radioiodine-administered activity was obtained (-21.1 ± 8.1%). Local symptom score demonstrated a more rapid reduction in group A (LAT+131I). In three cases, no 131I treatment was needed after LAT. In this pilot study, combined LAT/131I treatment induced faster and greater improvement of local and systemic symptoms compared to 131I only. This approach seems a possible alternative to thyroidectomy in patients at refusal of surgery.

The utility of radioiodine uptake and thyroid scintigraphy in the diagnosis and management of hyperthyroidism.

PubMed

Okosieme, O E; Chan, D; Price, S A; Lazarus, J H; Premawardhana, L D K E

2010-01-01

The value and practice of thyroid radionuclide imaging in the diagnosis and management of hyperthyroidism is unsettled. Our objectives were to determine the influence of thyroid uptake and scintigraphy on the diagnosis of hyperthyroidism and the prediction of outcome following radioiodine therapy. We reviewed records and scintigraphic studies on 881 hyperthyroid patients carried out between 2000 and 2007. The agreement between the clinical and scintigraphic diagnosis was evaluated by kappa statistics. We determined the relationship between 4-h (123)I uptake and the outcome of (131)I treatment in 626 patients. A multiple logistic regression model was used to determine variables influencing treatment outcome in 1 year. The diagnostic categories were Graves' disease (GD, n = 383), toxic multinodular goitre (n = 253), solitary toxic nodule (n = 164) and Graves' disease coexisting with nodules (n = 81). The mean age of the patients was 58 +/- 17, (M:F 160:721). There was good agreement between clinical and scintigraph diagnosis (K = 0.60, 95% CI 0.57-0.64, P < 0.001); and they were correctly matched in 74%; mismatched in 6% and indeterminate in 20% of patients. Treatment outcome was not associated with scintigraph diagnosis (P = 0.98) or radioiodine uptake at 4 h (P = 0.2). The use of antithyroid medications before treatment predicted treatment failure (odds ratio 2.0, 95% CI 1.2-3.6, P = 0.01). Thyroid scintigraphy and uptake studies did not influence diagnosis or treatment outcomes in most cases of hyperthyroidism. Our findings in this retrospective study do not justify their routine use. Selective scanning will reduce cost and exposure to radioisotopes without compromising diagnostic accuracy or treatment outcomes.

Twenty-five years after Chernobyl: outcome of radioiodine treatment in children and adolescents with very high-risk radiation-induced differentiated thyroid carcinoma.

PubMed

Reiners, Christoph; Biko, Johannes; Haenscheid, Heribert; Hebestreit, Helge; Kirinjuk, Stalina; Baranowski, Oleg; Marlowe, Robert J; Demidchik, Ewgeni; Drozd, Valentina; Demidchik, Yuri

2013-07-01

After severe reactor emergencies with release of radioactive iodine, elevated thyroid cancer risk in children and adolescents is considered the main health consequence for the population exposed. We studied thyroid cancer outcome after 11.3 years' median follow-up in a selected, very high-risk cohort, 234 Chernobyl-exposed Belarusian children and adolescents undergoing postsurgical radioiodine therapy (RIT) in Germany. Cumulatively 100 children with or (without; n = 134) distant metastasis received a median 4 (2) RITs and 16.9 (6.6) GBq, corresponding to 368 (141) MBq/kg iodine-131. Outcomes were response to therapy and disease status, mortality, and treatment toxicity. Of 229 patients evaluable for outcome, 147 (64.2%) attained complete remission [negative iodine-131 whole-body scan and TSH-stimulated serum thyroglobulin (Tg) < 1 μg /L], 69 (30.1%) showed nearly complete remission (complete response, except stimulated Tg 1-10 μg/L), and 11 (4.8%) had partial remission (Tg > 10 μg/L, decrease from baseline in radioiodine uptake intensity in ≥ 1 focus, in tumor volume or in Tg). Except for 2 recurrences (0.9%) after partial remission, no recurrences, progression, or disease-specific mortality were noted. One patient died of lung fibrosis 17.5 years after therapy, 2 of apparently thyroid cancer-unrelated causes. The only RIT side effect observed was pulmonary fibrosis in 5 of 69 patients (7.2%) with disseminated lung metastases undergoing intensive pulmonary surveillance. Experience of a large, very high-risk pediatric cohort with radiation-induced differentiated thyroid carcinoma suggests that even when such disease is advanced and initially suboptimally treated, response to subsequent RIT and final outcomes are mostly favorable.

Unprecedented homotopy perturbation method for solving nonlinear equations in the enzymatic reaction of glucose in a spherical matrix.

PubMed

Saranya, K; Mohan, V; Kizek, R; Fernandez, C; Rajendran, L

2018-02-01

The theory of glucose-responsive composite membranes for the planar diffusion and reaction process is extended to a microsphere membrane. The theoretical model of glucose oxidation and hydrogen peroxide production in the chitosan-aliginate microsphere has been discussed in this manuscript for the first time. We have successfully reported an analytical derived methodology utilizing homotopy perturbation to perform the numerical simulation. The influence and sensitive analysis of various parameters on the concentrations of gluconic acid and hydrogen peroxide are also discussed. The theoretical results enable to predict and optimize the performance of enzyme kinetics.

Photoaffinity analogues of methotrexate as folate antagonist binding probes. 2. Transport studies, photoaffinity labeling, and identification of the membrane carrier protein for methotrexate from murine L1210 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Price, E.M.; Freisheim, J.H.

1987-07-28

A membrane-derived component of the methotrexate/one-carbon-reduced folate transport system in murine L1210 cells has been identified by using a photoaffinity analogue of methotrexate. The compound, a radioiodinated 4-azidosalicylyl derivative of the lysine analogue of methotrexate, is transported into murine L1210 cells in a temperature-dependent, sulfhydryl reagent inhibitable manner with a K/sub t/ of 506 +/- 79 nM and a V/sub max/ of 17.9 +/- 4.2 pmol min/sup -1/ (mg of total cellular protein)/sup -1/. Uptake of the iodinated compound at 200 nM is inhibited by low amounts of methotrexate. The parent compounds of the iodinated photoprobe inhibit (/sup 3/H)methotrexate uptake,more » with the uniodinated 4-azidosalicylyl derivative exhibiting a K/sub i/ of 66 +/- 21 nM. UV irradiation, at 4 /sup 0/C, of a cell suspension that had been incubated with the probe results in the covalent modification of a 46K-48K protein. This can be demonstrated when the plasma membranes from the labeled cells are analyzed via sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Labeling of this protein occurs half-maximally at a reagent concentration that correlates with the K/sub t/ for transport of the iodinated compound. Protection against labeling of this protein by increasing amounts of methotrexate parallels the concentration dependence of inhibition of photoprobe uptake by methotrexate. Evidence that, in the absence of irradiation and at 37/sup 0/C, the iodinated probe is actually internalized is demonstrated by the labeling of two soluble proteins (M/sub r/ 38K and 21K) derived from the cell homogenate supernatant.« less

Discrimination of the glucose and the white sugar based on the pulsed laser-induced photoacoustic technique

NASA Astrophysics Data System (ADS)

Ren, Zhong; Liu, Guodong

2017-08-01

In this study, to discriminate the glucose and the white sugar gradient in the food, a noninvasive optical detection system based on pulsed laser-induced photoacoustic technique was developed. Meanwhile, the Nd: YAG 532nm pumped OPO pulsed laser was used as the excitation light source to generate of the photoacoustic signals of the glucose and white sugar. The focused ultrasonic transducer with central detection frequency of 1MHz was used to capture the photoacoustic signals. In experiments, the real-time photoacoustic signals of the glucose and the white sugar aqueous solutions were gotten and compared with each other. In addition, to discriminate the difference of the characteristic photoacoustic signals between both of them, the difference spectrum and the first order derivative technique between the peak-to-peak photoacoustic signals of the water and that of the glucose and white sugar were employed. The difference characteristic photoacoustic wavelengths between the glucose and the white sugar were found based on the established photoacoustic detection system. This study provides the potential possibility for the discrimination of the glucose and the white sugar by using the photoacoustic detection method.

Myeloid-Cell-Derived VEGF Maintains Brain Glucose Uptake and Limits Cognitive Impairment in Obesity.

PubMed

Jais, Alexander; Solas, Maite; Backes, Heiko; Chaurasia, Bhagirath; Kleinridders, André; Theurich, Sebastian; Mauer, Jan; Steculorum, Sophie M; Hampel, Brigitte; Goldau, Julia; Alber, Jens; Förster, Carola Y; Eming, Sabine A; Schwaninger, Markus; Ferrara, Napoleone; Karsenty, Gerard; Brüning, Jens C

2016-05-05

High-fat diet (HFD) feeding induces rapid reprogramming of systemic metabolism. Here, we demonstrate that HFD feeding of mice downregulates glucose transporter (GLUT)-1 expression in blood-brain barrier (BBB) vascular endothelial cells (BECs) and reduces brain glucose uptake. Upon prolonged HFD feeding, GLUT1 expression is restored, which is paralleled by increased expression of vascular endothelial growth factor (VEGF) in macrophages at the BBB. In turn, inducible reduction of GLUT1 expression specifically in BECs reduces brain glucose uptake and increases VEGF serum concentrations in lean mice. Conversely, myeloid-cell-specific deletion of VEGF in VEGF(Δmyel) mice impairs BBB-GLUT1 expression, brain glucose uptake, and memory formation in obese, but not in lean mice. Moreover, obese VEGF(Δmyel) mice exhibit exaggerated progression of cognitive decline and neuroinflammation on an Alzheimer's disease background. These experiments reveal that transient, HFD-elicited reduction of brain glucose uptake initiates a compensatory increase of VEGF production and assign obesity-associated macrophage activation a homeostatic role to restore cerebral glucose metabolism, preserve cognitive function, and limit neurodegeneration in obesity. Copyright © 2016 Elsevier Inc. All rights reserved.

Acrylamide: Inhibition of formation in processed food and mitigation of toxicity in cells, animals, and humans

USDA-ARS?s Scientific Manuscript database

Potentially toxic acrylamide is largely derived from the heat-unducing reactions between the amino group of the amino acid asparagine and carbonyl groups of glucose and fructose in plant derived foods including cereals, coffees, almonds, and potatoes. This review surveys and consolidates the followi...

Endothelial Cells Derived from the Blood-Brain Barrier and Islets of Langerhans Differ in their Response to the Effects of Bilirubin on Oxidative Stress Under Hyperglycemic Conditions.

PubMed

Kapitulnik, Jaime; Benaim, Clara; Sasson, Shlomo

2012-01-01

Unconjugated bilirubin (UCB) is a neurotoxic degradation product of heme. Its toxic effects include induction of apoptosis, and ultimately neuronal cell death. However, at low concentrations, UCB is a potent antioxidant that may protect cells and tissues against oxidative stress by neutralizing toxic metabolites such as reactive oxygen species (ROS). High glucose levels (hyperglycemia) generate reactive metabolites. Endothelial cell dysfunction, an early vascular complication in diabetes, has been associated with hyperglycemia-induced oxidative stress. Both glucose and UCB are substrates for transport proteins in microvascular endothelial cells of the blood-brain barrier (BBB). In the current study we show that UCB (1-40 μM) induces apoptosis and reduces survival of bEnd3 cells, a mouse brain endothelial cell line which serves as an in vitro model of the BBB. These deleterious effects of UCB were enhanced in the presence of high glucose (25 mM) levels. Interestingly, the bEnd3 cells exhibited an increased sensitivity to the apoptotic effects of UCB when compared to the MS1 microcapillary endothelial cell line. MS1 cells originate from murine pancreatic islets of Langerhans, and are devoid of the barrier characteristics of BBB-derived endothelial cells. ROS production was increased in both bEnd3 and MS1 cells exposed to high glucose, as compared with cells exposed to normal (5.5 mM) glucose levels. While UCB (0.1-40 μM) did not alter ROS production in cells exposed to normal glucose, relatively low ("physiological") UCB concentrations (0.1-5 μM) attenuated ROS generation in both cell lines exposed to high glucose levels. Most strikingly, higher UCB concentrations (20-40 μM) increased ROS generation in bEnd3 cells exposed to high glucose, but not in similarly treated MS1 cells. These results may be of critical importance for understanding the vulnerability of the BBB endothelium upon exposure to increasing UCB levels under hyperglycemic conditions.

Endothelial Cells Derived from the Blood-Brain Barrier and Islets of Langerhans Differ in their Response to the Effects of Bilirubin on Oxidative Stress Under Hyperglycemic Conditions

PubMed Central

Kapitulnik, Jaime; Benaim, Clara; Sasson, Shlomo

2012-01-01

Unconjugated bilirubin (UCB) is a neurotoxic degradation product of heme. Its toxic effects include induction of apoptosis, and ultimately neuronal cell death. However, at low concentrations, UCB is a potent antioxidant that may protect cells and tissues against oxidative stress by neutralizing toxic metabolites such as reactive oxygen species (ROS). High glucose levels (hyperglycemia) generate reactive metabolites. Endothelial cell dysfunction, an early vascular complication in diabetes, has been associated with hyperglycemia-induced oxidative stress. Both glucose and UCB are substrates for transport proteins in microvascular endothelial cells of the blood-brain barrier (BBB). In the current study we show that UCB (1–40 μM) induces apoptosis and reduces survival of bEnd3 cells, a mouse brain endothelial cell line which serves as an in vitro model of the BBB. These deleterious effects of UCB were enhanced in the presence of high glucose (25 mM) levels. Interestingly, the bEnd3 cells exhibited an increased sensitivity to the apoptotic effects of UCB when compared to the MS1 microcapillary endothelial cell line. MS1 cells originate from murine pancreatic islets of Langerhans, and are devoid of the barrier characteristics of BBB-derived endothelial cells. ROS production was increased in both bEnd3 and MS1 cells exposed to high glucose, as compared with cells exposed to normal (5.5 mM) glucose levels. While UCB (0.1–40 μM) did not alter ROS production in cells exposed to normal glucose, relatively low (“physiological”) UCB concentrations (0.1–5 μM) attenuated ROS generation in both cell lines exposed to high glucose levels. Most strikingly, higher UCB concentrations (20–40 μM) increased ROS generation in bEnd3 cells exposed to high glucose, but not in similarly treated MS1 cells. These results may be of critical importance for understanding the vulnerability of the BBB endothelium upon exposure to increasing UCB levels under hyperglycemic conditions. PMID:22811666

Health technology assessment review: Computerized glucose regulation in the intensive care unit - how to create artificial control

PubMed Central

2009-01-01

Current care guidelines recommend glucose control (GC) in critically ill patients. To achieve GC, many ICUs have implemented a (nurse-based) protocol on paper. However, such protocols are often complex, time-consuming, and can cause iatrogenic hypoglycemia. Computerized glucose regulation protocols may improve patient safety, efficiency, and nurse compliance. Such computerized clinical decision support systems (Cuss) use more complex logic to provide an insulin infusion rate based on previous blood glucose levels and other parameters. A computerized CDSS for glucose control has the potential to reduce overall workload, reduce the chance of human cognitive failure, and improve glucose control. Several computer-assisted glucose regulation programs have been published recently. In order of increasing complexity, the three main types of algorithms used are computerized flowcharts, Proportional-Integral-Derivative (PID), and Model Predictive Control (MPC). PID is essentially a closed-loop feedback system, whereas MPC models the behavior of glucose and insulin in ICU patients. Although the best approach has not yet been determined, it should be noted that PID controllers are generally thought to be more robust than MPC systems. The computerized Cuss that are most likely to emerge are those that are fully a part of the routine workflow, use patient-specific characteristics and apply variable sampling intervals. PMID:19849827

Photoacoustic experiments of glucose aqueous solution based on pulsed laser induced ultrasonic technique

NASA Astrophysics Data System (ADS)

Ren, Zhong; Liu, Guodong; Huang, Zheng; Ding, Yu

2017-10-01

In this work, to further find the characteristic wavelengths of glucose, the photoacoustic experiments of glucose aqueous solutions were performed by using the photoacoustic technique. The photoacoustic detection system was established by the Q switched Nd: YAG OPO pulsed laser and ultrasonic detector with central frequency of 20MHz. The photoacoustic signals of samples were averaged with 512 times. Baed on the established photoacoustic detection system, the time-resolved photoacoustic signals of glucose with different concentrations at the different wavelengths were captured by the digital oscilloscope, and compared with that of the pure water. In order to get the characteristic wavelengths of glucose, the photoacoustic peak-to-peak values of glucose with different concentrations at the wavelength from 1350nm to 2100nm were obtained, and the difference spectral was gotten by using the difference method between the glucose solutions and pure water. Moreover, the first order derivation method was also used. The wavelength of 1650nm and 1850nm was chosen as the characteristic wavelengths of glucose. The linear fitting equation was established to verify the availability of two characteristic wavelengths. The average prediction error results showed that the choosing of the characteristic wavelength of 1650nm and 1850nm is available.

Striking differences in glucose and lactate levels between brain extracellular fluid and plasma in conscious human subjects: effects of hyperglycemia and hypoglycemia.

PubMed

Abi-Saab, Walid M; Maggs, David G; Jones, Tim; Jacob, Ralph; Srihari, Vinod; Thompson, James; Kerr, David; Leone, Paola; Krystal, John H; Spencer, Dennis D; During, Matthew J; Sherwin, Robert S

2002-03-01

Brain levels of glucose and lactate in the extracellular fluid (ECF), which reflects the environment to which neurons are exposed, have never been studied in humans under conditions of varying glycemia. The authors used intracerebral microdialysis in conscious human subjects undergoing electrophysiologic evaluation for medically intractable epilepsy and measured ECF levels of glucose and lactate under basal conditions and during a hyperglycemia-hypoglycemia clamp study. Only measurements from nonepileptogenic areas were included. Under basal conditions, the authors found the metabolic milieu in the brain to be strikingly different from that in the circulation. In contrast to plasma, lactate levels in brain ECF were threefold higher than glucose. Results from complementary studies in rats were consistent with the human data. During the hyperglycemia-hypoglycemia clamp study the relationship between plasma and brain ECF levels of glucose remained similar, but changes in brain ECF glucose lagged approximately 30 minutes behind changes in plasma. The data demonstrate that the brain is exposed to substantially lower levels of glucose and higher levels of lactate than those in plasma; moreover, the brain appears to be a site of significant anaerobic glycolysis, raising the possibility that glucose-derived lactate is an important fuel for the brain.

Biosynthesis of the trehalase inhibitor trehazolin.

PubMed

Sugiyama, Yasumasa; Nagasawa, Hiromichi; Suzuki, Akinori; Sakuda, Shohei

2002-03-01

Trehazolin (1) is a trehalase inhibitor produced by Micromonospora coriacea. Biosynthesis of 1 was studied by feeding experiments with a variety of labeled precursors. Feeding experiments with [1-13C]- and [6-13C]-D-glucose revealed that the carbon skeletons of both a glucose residue and a cyclopentane ring moiety in 1 were each derived from glucose, and that C-C bond formation between C-1 and C-5 of glucose occurred during the cyclopentane ring formation. Furthermore, an experiment with [guanidino-13C, 15N2]-L-arginine revealed that two nitrogen atoms and a quaternary carbon atom involved in the aminooxazoline moiety of 1 originated from an amidino group of arginine. Further feeding experiments with [1-2H]-, [2-2H]-, [4-2H]-, [6,6-2H2]- and [1,2,3,4,5,6,6-2H7]-D-glucose as well as [1-13C]-D-fructose showed that deuteriums on C-1, C-3, C-4 and C-6 of glucose were retained during the formation of the cyclopentane ring moiety of 1.

Development of glucose-responsive 'smart' insulin systems.

PubMed

Rege, Nischay K; Phillips, Nelson F B; Weiss, Michael A

2017-08-01

The complexity of modern insulin-based therapy for type I and type II diabetes mellitus and the risks associated with excursions in blood-glucose concentration (hyperglycemia and hypoglycemia) have motivated the development of 'smart insulin' technologies (glucose-responsive insulin, GRI). Such analogs or delivery systems are entities that provide insulin activity proportional to the glycemic state of the patient without external monitoring by the patient or healthcare provider. The present review describes the relevant historical background to modern GRI technologies and highlights three distinct approaches: coupling of continuous glucose monitoring (CGM) to deliver devices (algorithm-based 'closed-loop' systems), glucose-responsive polymer encapsulation of insulin, and molecular modification of insulin itself. Recent advances in GRI research utilizing each of the three approaches are illustrated; these include newly developed algorithms for CGM-based insulin delivery systems, glucose-sensitive modifications of existing clinical analogs, newly developed hypoxia-sensitive polymer matrices, and polymer-encapsulated, stem-cell-derived pancreatic β cells. Although GRI technologies have yet to be perfected, the recent advances across several scientific disciplines that are described in this review have provided a path towards their clinical implementation.

Protective Effects of Ferulic Acid on High Glucose-Induced Protein Glycation, Lipid Peroxidation, and Membrane Ion Pump Activity in Human Erythrocytes

PubMed Central

Sompong, Weerachat; Cheng, Henrique; Adisakwattana, Sirichai

2015-01-01

Ferulic acid (FA) is the ubiquitous phytochemical phenolic derivative of cinnamic acid. Experimental studies in diabetic models demonstrate that FA possesses multiple mechanisms of action associated with anti-hyperglycemic activity. The mechanism by which FA prevents diabetes-associated vascular damages remains unknown. The aim of study was to investigate the protective effects of FA on protein glycation, lipid peroxidation, membrane ion pump activity, and phosphatidylserine exposure in high glucose-exposed human erythrocytes. Our results demonstrated that FA (10-100 μM) significantly reduced the levels of glycated hemoglobin (HbA1c) whereas 0.1-100 μM concentrations inhibited lipid peroxidation in erythrocytes exposed to 45 mM glucose. This was associated with increased glucose consumption. High glucose treatment also caused a significant reduction in Na+/K+-ATPase activity in the erythrocyte plasma membrane which could be reversed by FA. Furthermore, we found that FA (0.1-100 μM) prevented high glucose-induced phosphatidylserine exposure. These findings provide insights into a novel mechanism of FA for the prevention of vascular dysfunction associated with diabetes. PMID:26053739

Glutamatergic Receptor Activation in the Commisural Nucleus Tractus Solitarii (cNTS) Mediates Brain Glucose Retention (BGR) Response to Anoxic Carotid Chemoreceptor (CChr) Stimulation in Rats.

PubMed

Cuéllar, R; Montero, S; Luquín, S; García-Estrada, J; Dobrovinskaya, O; Melnikov, V; Lemus, M; de Álvarez-Buylla, E Roces

2015-01-01

Glutamate, released from central terminals of glossopharyngeal nerve, is a major excitatory neurotransmitter of commissural nucleus tractus solitarii (cNTS) afferent terminals, and brain derived neurotrophic factor (BDNF) has been shown to attenuate glutamatergic AMPA currents in NTS neurons. To test the hypothesis that AMPA contributes to glucose regulation in vivo modulating the hyperglycemic reflex with brain glucose retention (BGR), we microinjected AMPA and NBQX (AMPA antagonist) into the cNTS before carotid chemoreceptor stimulation in anesthetized normal Wistar rats, while hyperglycemic reflex an brain glucose retention (BGR) were analyzed. To investigate the underlying mechanisms, GluR2/3 receptor and c-Fos protein expressions in cNTS neurons were determined. We showed that AMPA in the cNTS before CChr stimulation inhibited BGR observed in aCSF group. In contrast, NBQX in similar conditions, did not modify the effects on glucose variables observed in aCSF control group. These experiments suggest that glutamatergic pathways, via AMPA receptors, in the cNTS may play a role in glucose homeostasis.

A non-invasive photoacoustic and ultrasonic method for the measurement of glucose solution concentration

NASA Astrophysics Data System (ADS)

Zhao, Siwei; Tao, Wei; He, Qiaozhi; Zhao, Hui; Cao, Wenwu

2017-03-01

Diabetes mellitus (DM) is a chronic disease affecting nearly 400 million people worldwide. In order to manage the disease, patients need to monitor the blood glucose level by puncturing the finger several times a day, which is uncomfortable and inconvenient. We present here a potential non-invasive monitoring method based on the velocity of ultrasonic waves generated in glucose solution by the photoacoustic principal, which can recognize the glucose concentration down to 20mg/dL. In order to apply this method to warm bodies, we carefully designed the experiment and performed measurements from 30 °C to 50 °C to generate a set of calibration curves, which may be used by engineers to build devices. Most importantly, we have theoretically explained the relationship between the compressibility and the glucose concentration. Our results show that the compressibility of solution decreases with the glucose concentration, which clarified the controversy between theory and experiment results in the literature. The derived formula is generally validity, which can be used to nondestructively measure solution concentration for other types of solutions using photoacoustic principle.

Glucose Limitation Alters Glutamine Metabolism in MUC1-Overexpressing Pancreatic Cancer Cells.

PubMed

Gebregiworgis, Teklab; Purohit, Vinee; Shukla, Surendra K; Tadros, Saber; Chaika, Nina V; Abrego, Jaime; Mulder, Scott E; Gunda, Venugopal; Singh, Pankaj K; Powers, Robert

2017-10-06

Pancreatic cancer cells overexpressing Mucin 1 (MUC1) rely on aerobic glycolysis and, correspondingly, are dependent on glucose for survival. Our NMR metabolomics comparative analysis of control (S2-013.Neo) and MUC1-overexpressing (S2-013.MUC1) cells demonstrates that MUC1 reprograms glutamine metabolism upon glucose limitation. The observed alteration in glutamine metabolism under glucose limitation was accompanied by a relative decrease in the proliferation of MUC1-overexpressing cells compared with steady-state conditions. Moreover, glucose limitation induces G1 phase arrest where S2-013.MUC1 cells fail to enter S phase and synthesize DNA because of a significant disruption in pyrimidine nucleotide biosynthesis. Our metabolomics analysis indicates that glutamine is the major source of oxaloacetate in S2-013.Neo and S2-013.MUC1 cells, where oxaloacetate is converted to aspartate, an important metabolite for pyrimidine nucleotide biosynthesis. However, glucose limitation impedes the flow of glutamine carbons into the pyrimidine nucleotide rings and instead leads to a significant accumulation of glutamine-derived aspartate in S2-013.MUC1 cells.

Stimulation of glucose phosphorylation by fructose in isolated rat hepatocytes.

PubMed

Van Schaftingen, E; Vandercammen, A

1989-01-15

The phosphorylation of glucose was measured by the formation of [3H]H2O from [2-3H]glucose in suspensions of freshly isolated rat hepatocytes. Fructose (0.2 mM) stimulated 2-4-fold the rate of phosphorylation of 5 mM glucose although not of 40 mM glucose, thus increasing the apparent affinity of the glucose phosphorylating system. A half-maximal stimulatory effect was observed at about 50 microM fructose. Stimulation was maximal 5 min after addition of the ketose and was stable for at least 40 min, during which period 60% of the fructose was consumed. The effect of fructose was reversible upon removal of the ketose. Sorbitol and tagatose were as potent as fructose in stimulating the phosphorylation of 5 mM glucose. D-Glyceraldehyde also had a stimulatory effect but at tenfold higher concentrations. In contrast, dihydroxyacetone had no significant effect and glycerol inhibited the detritiation of glucose. Oleate did not affect the phosphorylation of glucose, even in the presence of fructose, although it stimulated the formation of ketone bodies severalfold, indicating that it was converted to its acyl-CoA derivative. These results allow the conclusion that fructose stimulates glucokinase in the intact hepatocyte. They also suggest that this effect is mediated through the formation of fructose 1-phosphate, which presumably interacts with a competitive inhibitor of glucokinase other than long-chain acyl-CoAs.

Properties of maltodextrins and glucose syrups in experiments in vitro and in the diets of laboratory animals, relating to dental health.

PubMed

Grenby, T H; Mistry, M

2000-10-01

The objective of the study was to examine the cariogenic potentials of maltodextrins and glucose syrups (two glucose polymers derived from starch) using a range of techniques in vitro and in laboratory animals. The experimental methods used were: (1) measurement of acid production from glucose syrups and maltodextrins by human dental plaque micro-organisms; (2) evaluation of the role salivary alpha-amylase in degrading oligosaccharides (degree of polymerisation > 3) in the glucose polymers, estimating the products by HPLC; (3) assessment of the fermentability of trioses relative to maltose; (4) measurement of dental caries levels in three large-scale studies in laboratory rats fed on diets containing the glucose polymers. It was found that acid production from the glucose polymers increased as their higher saccharide content fell. Salivary alpha-amylase rapidly degraded the oligosaccharides (degree of polymerisation > 3), mainly to maltose and maltotriose. In the presence of oral micro-organisms, maltotriose took longer to ferment than maltose, but by the end of a 2 h period the total amount of acid produced was the same from both. Incorporated into the diets in solid form, the glucose syrups and maltodextrins were associated with unexpectedly high levels of dental caries. In conclusion, the findings were unforeseen in the light of earlier data that a glucose syrup was less cariogenic than sucrose.

Macrocyclic triamine derived glucose analogues for 99m Tc(CO)3 labeling: synthesis and biological evaluation as potential tumor-imaging agents.

PubMed

Liu, Teli; Gan, Qianqian; Zhang, Junbo

2017-02-01

[ 99m Tc(CO) 3 (H 2 O) 3 ] + has attracted great attention among 99m Tc-labeling techniques, due to its ease of preparation, readily substituted water molecules of the precursor fac-[ 99m Tc(CO) 3 (H 2 O) 3 ] + by a variety of functional groups, small size and inertness. Bifunctional chelator based on a macrocyclic polyamine framework shows easy complexation with [ 99m Tc(CO) 3 (H 2 O) 3 ] + to produce stable complex. In this study, two novel 1, 5, 9-triazacyclododecane derivatives containing a glucose group (6 and 7) were successfully synthesized by reacting different glucose-azides with alkyne-[12]aneN 3 via the so-called click chemistry and radiolabeled with [ 99m Tc(CO) 3 (H 2 O) 3 ] + to form 99m Tc(CO) 3 -6 (C-1-substituted complex) and 99m Tc(CO) 3 -7 (C-2-substituted complex) in high yields. The complexes were stable in vitro over 6 h when incubated in saline at room temperature and in mouse serum at 37 °C. The partition coefficient results showed that they were hydrophilic. The biodistribution studies in Kunming mice bearing S 180 tumor showed both complexes showed accumulation in the tumor. Between them, 99m Tc(CO) 3 -7 had the advantages of much higher tumor uptake and tumor/muscle ratio. Compared with other reported 99m Tc-radiolabeled glucose derivatives, 99m Tc(CO) 3 -7 also showed a higher tumor uptake and tumor/muscle ratio, suggesting it would be a potential candidate for further development as a tumor-imaging agent. © 2017 John Wiley & Sons A/S.

Determination of NIR informative wavebands for transmission non-invasive blood glucose measurement using a Fourier transform spectrometer

NASA Astrophysics Data System (ADS)

Yang, Wenming; Liao, Ningfang; Cheng, Haobo; Li, Yasheng; Bai, Xueqiong; Deng, Chengyang

2018-03-01

Non-invasive blood glucose measurement using near infrared (NIR) spectroscopy relies on wavebands that provide reliable information about spectral absorption. In this study, we investigated wavebands which are informative for blood glucose in the NIR shortwave band (900˜1450 nm) and the first overtone band (1450˜1700 nm) through a specially designed NIR Fourier transform spectrometer (FTS), which featured a test fixture (where a sample or subject's finger could be placed) and all-reflective optics, except for a Michelson structure. Different concentrations of glucose solution and seven volunteers who had undergone oral glucose tolerance tests (OGTT) were studied to acquire transmission spectra in the shortwave band and the first overtone band. Characteristic peaks of glucose absorption were identified from the spectra of glucose aqueous solution by second-order derivative processing. The wavebands linked to blood glucose were successfully estimated through spectra of the middle fingertip of OGTT participants by a simple linear regression and correlation coefficient. The light intensity difference showed that glucose absorption in the first overtone band was much more prominent than it was in the shortwave band. The results of the SLR model established from seven OGTTs in total on seven participants enabled a positive estimation of the glucose-linked wavelength. It is suggested that wavebands with prominent characteristic peaks, a high correlation coefficient between blood glucose and light intensity difference and a relatively low standard deviation of predicted values will be the most informative wavebands for transmission non-invasive blood glucose measurement methods. This work provides a guidance for waveband selection for the development of non-invasive NIR blood glucose measurement.

Glucose tolerance status in 510 children and adolescents attending an obesity clinic in Central Italy.

PubMed

Brufani, Claudia; Ciampalini, Paolo; Grossi, Armando; Fiori, Rossana; Fintini, Danilo; Tozzi, Alberto; Cappa, Marco; Barbetti, Fabrizio

2010-02-01

Childhood obesity is epidemic in developed countries and is accompanied by an increase in the prevalence of type 2 diabetes (T2DM). Establish prevalence of glucose metabolism alterations in a large sample of overweight/obese children and adolescents from Central Italy. The study group included 510 overweight/obese subjects (3-18 yr). Oral glucose tolerance test (OGTT) was performed with glucose and insulin determination. Homeostatic model assessment of insulin resistance (HOMA-IR) and insulin sensitivity index (ISI) were derived from fasting and OGTT measurements. Beta-cell function was estimated by insulinogenic index. Fat mass was measured by dual-energy x-ray absorptiometry. Glucose metabolism alterations were detected in 12.4% of patients. Impaired glucose tolerance (IGT) was the most frequent alteration (11.2%), with a higher prevalence in adolescents than in children (14.8 vs. 4.1%, p < 0.001); silent T2DM was identified in two adolescents (0.4%). HOMA-IR and glucose-stimulated insulin levels were higher in patients with IGT than individuals with normal glucose tolerance (HOMA-IR = 4.4 +/- 2.5 vs. 3.4 +/- 2.3, p = 0.001). Fat mass percentage and insulinogenic index were not different between the two groups. In multivariate analysis, age, fasting glucose, and insulin resistance influenced independently plasma glucose at 120 min of OGTT. Individuals with combined impaired fasting glucose/IGT (IFG/IGT) and T2DM were older and had reduced plasma insulin values at OGTT when compared to patients with simple IGT. Glucose metabolism alterations are frequently found among children and adolescents with overweight/obesity from Central Italy. Age, fasting glucose, and insulin resistance are main predictors of IGT. We suggest the use of OGTT as a screening tool in obese European adolescents.

Imaging agent and method of use

DOEpatents

Wieland, D.M.; Brown, L.E.; Beierwaltes, W.H.; Wu, J.L.

1986-04-22

A new radiopharmaceutical composition for use in nuclear medicine comprises a radioiodinated meta-iodobenzylguanidine. The composition is used as an imaging agent for the heart, adrenal medulla, and tumors of the adrenal medulla and can be used for treatment of tumors of the adrenal medulla. No Drawings

NEVADA TEST SITE EXPERIMENTAL FARM: SUMMARY REPORT 1963-1981

EPA Science Inventory

This report summarizes the findings from experiments conducted at the Experimental Dairy Farm located on the Nevada Test Site. These experiments included the air-forage-cow-milk transport of the radioiodines, and the metabolism and milk transfer of other fission products and seve...

Iodine Symporter Targeting with 124I/131I Theranostics.

PubMed

Nagarajah, James; Janssen, Marcel; Hetkamp, Philipp; Jentzen, Walter

2017-09-01

Theranostics, a modern approach combining therapeutics and diagnostics, is among the most promising concepts in nuclear medicine for optimizing and individualizing treatments for many cancer entities. Theranostics has been used in clinical routines in nuclear medicine for more than 60 y-as 131 I for diagnostic and therapeutic purposes in thyroid diseases. In this minireview, we provide a survey of the use of 2 different radioiodine isotopes for targeting the sodium-iodine symporter in thyroid cancer and nonthyroidal neoplasms as well as a brief summary of theranostics for neuroendocrine neoplasms and metastatic castration-refractory prostate cancer. In particular, we discuss the role of 124 I-based dosimetry in targeting of the sodium-iodine symporter and describe the clinical application of 124 I dosimetry in a patient who had radioiodine-refractory thyroid cancer and who underwent a redifferentiation treatment with the mitogen-activated extracellular signal-related kinase kinase inhibitor trametinib. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Muscarinic cholinergic receptor binding: in vivo depiction using single photon emission computed tomography and radioiodinated quinuclidinyl benzilate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Drayer, B.; Jaszczak, R.; Coleman, E.

1982-06-01

An attempt was made to characterize, in vivo, specific binding to the muscarinic cholinergic receptor in the calf using the radioiodinated ligand quinuclidinyl benzilate (/sup 123/I-OH-QNB) and single photon detection emission computed tomography (SPECT). The supratentorial brain activity was significantly increased after the intravenous infusion of /sup 123/I-OH-QNB as compared to free /sup 123/I. Scopolamine, a muscarinic cholinergic receptor antagonist, decreased the measured brain activity when infused prior to /sup 123/I-OH-QNB consistent with pharmacologic blockade of specific receptor binding. Quantitative in vitro tissue distribution studies obtained following SPECT imaging were consistent with regionally distinct specific receptor binding in the striatummore » and cortical gray matter, nonspecific binding in the cerebellum, and pharmacologic blockade of specific binding sites with scopolamine. Although /sup 123/I-OH-QNB is not the ideal radioligand, our limited success will hopefully encourage the development of improved binding probes for SPECT imaging and quantitation.« less

Tethered Hsp90 Inhibitors Carrying Optical or Radioiodinated Probes Reveal Selective Internalization of Ectopic Hsp90 in Malignant Breast Tumor Cells

PubMed Central

Barrott, Jared J.; Hughes, Philip F.; Osada, Takuya; Yang, Xiao-Yi; Hartman, Zachary C.; Loiselle, David R.; Spector, Neil L.; Neckers, Len; Rajaram, Narasimhan; Hu, Fangyao; Ramanujam, Nimmi; Vaidyanathan, Ganesan; Zalutsky, Michael R.; Lyerly, H. Kim; Haystead, Timothy A.

2013-01-01

Summary Hsp90 inhibitors have demonstrated unusual selectivity for tumor cells despite its ubiquitous expression. This phenomenon has remained unexplained but could be influenced by ectopically expressed Hsp90 in tumors. We have synthesized novel Hsp90 inhibitors that can carry optical or radioiodinated probes via a PEG tether. We show that these tethered inhibitors selectively recognize cells expressing ectopic Hsp90 and become internalized. The internalization process is blocked by Hsp90 antibodies, suggesting that active cycling of the protein is occurring at the plasma membrane. In mice, we show exquisite accumulation of the fluor-tethered versions within breast tumors at very sensitive levels. Cell-based assays with the radiolabeled version showed picomolar detection in cells that express ectopic Hsp90. Our findings show that fluor-tethered or radiolabeled inhibitors targeting ectopic Hsp90 can be used to detect breast cancer malignancies through non-invasive imaging. PMID:24035283

Improved radioimmunotherapy of hematologic malignancies. [Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Press, O.W.

This research project proposes to develop novel new approaches of improving the radioimmunodetection and radioimmunotherapy of malignancies by augmenting retention of radioimmunoconjugates by tumor cells. The approaches shown to be effective in these laboratory experiments will subsequently be incorporated into out ongoing clinical trials in patients. Specific project objectives include: to study the rates of endocytosis, intracellular routing, and metabolic degradation of radiolabeled monoclonal antibodies targeting tumor-associated antigens on human leukemia and lymphoma cells; To examine the effects of lysosomotropic amines (e.g. chloroquine, amantadine), carboxylic ionophores (monensin, nigericin), and thioamides (propylthiouracil), on the retention of radiolabeled MoAbs by tumor cells;more » to examine the impact of newer radioiodination techniques (tyramine cellobiose, paraiodobenzoyl) on the metabolic degradation of radioiodinated antibodies; to compare the endocytosis, intracellular routing, and degradation of radioimmunoconjugates prepared with different radionuclides ({sup 131}Iodine, {sup 111}Indium, {sup 90}Yttrium, {sup 99m}Technetium, {sup 186}Rhenium); and to examine the utility of radioimmunoconjugates targeting oncogene products for the radioimmunotherapy and radioimmunoscintigraphy of cancer.« less

Improved radioimmunotherapy of hematologic malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Press, O.W.

This research project proposes to develop novel new approaches of improving the radioimmunodetection and radioimmunotherapy of malignancies by augmenting retention of radioimmunoconjugates by tumor cells. The approaches shown to be effective in these laboratory experiments will subsequently be incorporated into out ongoing clinical trials in patients. Specific project objectives include: to study the rates of endocytosis, intracellular routing, and metabolic degradation of radiolabeled monoclonal antibodies targeting tumor-associated antigens on human leukemia and lymphoma cells; To examine the effects of lysosomotropic amines (e.g. chloroquine, amantadine), carboxylic ionophores (monensin, nigericin), and thioamides (propylthiouracil), on the retention of radiolabeled MoAbs by tumor cells;more » to examine the impact of newer radioiodination techniques (tyramine cellobiose, paraiodobenzoyl) on the metabolic degradation of radioiodinated antibodies; to compare the endocytosis, intracellular routing, and degradation of radioimmunoconjugates prepared with different radionuclides ({sup 131}Iodine, {sup 111}Indium, {sup 90}Yttrium, {sup 99m}Technetium, {sup 186}Rhenium); and to examine the utility of radioimmunoconjugates targeting oncogene products for the radioimmunotherapy and radioimmunoscintigraphy of cancer.« less

Red cell changes in hyperthyroidism.

PubMed

How, J; Davidson, R J; Bewsher, P D

1979-10-01

The Coulter 'S' red cell profile was studied prospectively in 100 untreated non-anaemic hyperthyroid patients and followed up in 52 of them until they had become euthyroid with radio-iodine or carbimazole treatment. Serial haematological data were also obtained in 23 hyperthyroid patients during treatment with beta-adrenoreceptor blocking drug alone. The most significant finding was a low mean corpuscular volume (MCV) which was invariably present throughout the hyperthyroid state. Treatment with beta-adrenoreceptor blocking drugs did not significantly alter any of the red cell parameters. On the other hand, the MCV increased and was restored to normal with radio-iodine or carbimazole treatment although there was a lag period of about 6--8 weeks between achieving the euthyroid state and the normalisation of this red cell index. While none of the patients were aneaemic, the haemoglobin level rose significantly following effective anti-thyroid treatment. It is suggested that measurement of the MCV may have a useful role in the diagnosis of hyperthyroidism. 2 possible mechanisms leading to the observed red cell changes in hyperthyroidism are postulated.

Synchronous papillary carcinoma in thyroglossal duct cyst and thyroid gland: case report and review of literature.

PubMed

Cherian, Mathew Pynumootil; Nair, Balakrishnan; Thomas, Shaji; Somanathan, Thara; Sebastian, Paul

2009-10-01

We report a rare case of synchronous occurrence of thyroglossal duct cyst carcinoma and thyroid carcinoma and discuss its management in detail. A 59-year-old woman was clinically diagnosed to have a thyroglossal duct cyst and a solitary nodule. Fine-needle aspiration cytology revealed a papillary carcinoma in the thyroglossal duct cyst and a colloid in the thyroid nodule. Sistrunk's procedure along with a total thyroidectomy was performed followed by postoperative radioiodine ablation. Histopathologic examination revealed thyroglossal duct cyst carcinoma and bilateral foci of papillary carcinoma in the thyroid gland. She has remained free of disease on follow-up. Most cancers arising in thyroglossal duct cysts are of low risk, and Sistrunk's procedure is an adequate treatment for such cancers. However, for synchronously occurring cancers of the thyroglossal duct cyst and thyroid gland, or high-risk thyroglossal duct cyst cancers, more aggressive treatment comprising total thyroidectomy, Sistrunk's procedure, and radioiodine therapy is indicated. (c) 2009 Wiley Periodicals, Inc.

Sequestration of radioactive iodine in silver-palladium phases in commercial spent nuclear fuel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buck, Edgar C.; Mausolf, Edward J.; McNamara, Bruce K.

Radioactive iodine is the Achilles’ heel in the design for the safe geological disposal of spent UO2 nuclear fuel. Iodine’s high solubility and anticipated instant release during waste package compromise jeopardize performance assessment calculations. However, dissolution studies have indicated that the instant release fraction (IRF) of radioiodine (I) does not correlate with increasing fuel burn-up. In fact, there is a peak in the release iodine at around 50-60 Mwd/kgU and with increasing burn-up the instant release of iodine decreases. Detailed electron microscopy analysis of high burn-up fuel (~80 MWd/kgU) has revealed the presence of (Pd,Ag)(I,Br) nano-particles. As UO2 fuels aremore » irradiated, the Ag and Pd content increases, from 239Pu fission, enabling radioiodine to be retained. The occurrence of these phases in nuclear fuels may have significant implications for the long-term behavior of iodine.« less

Facile Fabrication of Nanofibrillated Chitin/Ag2O Heterostructured Aerogels with High Iodine Capture Efficiency.

PubMed

Gao, Runan; Lu, Yun; Xiao, Shaoliang; Li, Jian

2017-06-27

Nanofibrillated chitin/Ag 2 O aerogels were fabricated for radioiodine removal. Chitin was first fabricated into nanofibers with abundant acetyl amino groups (-NHCOCH 3 ) on the surface. Then, highly porous chitin nanofiber (ChNF) aerogels were obtained via freeze-drying. The ChNF aerogels exhibited a low bulk density of 2.19 mg/cm 3 and a high specific surface area of 179.71 m 2 /g. Ag 2 O nanoparticles were evenly anchored on the surfaces of ChNF scaffolds via strong interactions with -NHCOCH 3 groups, subsequently yielding Ag 2 O@ChNF heterostructured aerogels. The composites were used as efficient absorbents to remove radioiodine anions from water and capture a high amount of I 2 vapor in the forms of AgI and iodine molecules. The adsorption capacity of the composite monoliths can reach up to 2.81 mmol/g of I - anions. The high adsorbability of the composite monolithic aerogel signifies its potential applications in radioactive waste disposal.

Microbial Transformation of Iodine: From Radioisotopes to Iodine Deficiency.

PubMed

Yeager, Chris M; Amachi, Seigo; Grandbois, Russell; Kaplan, Daniel I; Xu, Chen; Schwehr, Kathy A; Santschi, Peter H

2017-01-01

Iodine is a biophilic element that is important for human health, both as an essential component of several thyroid hormones and, on the other hand, as a potential carcinogen in the form of radioiodine generated by anthropogenic nuclear activity. Iodine exists in multiple oxidation states (-1, 0, +1, +3, +5, and +7), primarily as molecular iodine (I 2 ), iodide (I - ), iodate [Formula: see text] , or organic iodine (org-I). The mobility of iodine in the environment is dependent on its speciation and a series of redox, complexation, sorption, precipitation, and microbial reactions. Over the last 15years, there have been significant advances in iodine biogeochemistry, largely spurred by renewed interest in the fate of radioiodine in the environment. We review the biogeochemistry of iodine, with particular emphasis on the microbial processes responsible for volatilization, accumulation, oxidation, and reduction of iodine, as well as the exciting technological potential of these fascinating microorganisms and enzymes. Copyright © 2017 Elsevier Inc. All rights reserved.

Hyperglycemic clamp and oral glucose tolerance test for 3-year prediction of clinical onset in persistently autoantibody-positive offspring and siblings of type 1 diabetic patients.

PubMed

Balti, Eric V; Vandemeulebroucke, Evy; Weets, Ilse; Van De Velde, Ursule; Van Dalem, Annelien; Demeester, Simke; Verhaeghen, Katrijn; Gillard, Pieter; De Block, Christophe; Ruige, Johannes; Keymeulen, Bart; Pipeleers, Daniel G; Decochez, Katelijn; Gorus, Frans K

2015-02-01

In preparation of future prevention trials, we aimed to identify predictors of 3-year diabetes onset among oral glucose tolerance test (OGTT)- and hyperglycemic clamp-derived metabolic markers in persistently islet autoantibody positive (autoAb(+)) offspring and siblings of patients with type 1 diabetes (T1D). The design is a registry-based study. Functional tests were performed in a hospital setting. Persistently autoAb(+) first-degree relatives of patients with T1D (n = 81; age 5-39 years). We assessed 3-year predictive ability of OGTT- and clamp-derived markers using receiver operating characteristics (ROC) and Cox regression analysis. Area under the curve of clamp-derived first-phase C-peptide release (AUC(5-10 min); min 5-10) was determined in all relatives and second-phase release (AUC(120-150 min); min 120-150) in those aged 12-39 years (n = 62). Overall, the predictive ability of AUC(5-10 min) was better than that of peak C-peptide, the best predictor among OGTT-derived parameters (ROC-AUC [95%CI]: 0.89 [0.80-0.98] vs 0.81 [0.70-0.93]). Fasting blood glucose (FBG) and AUC(5-10 min) provided the best combination of markers for prediction of diabetes within 3 years; (ROC-AUC [95%CI]: 0.92 [0.84-1.00]). In multivariate Cox regression analysis, AUC(5-10 min)) (P = .001) was the strongest independent predictor and interacted significantly with all tested OGTT-derived parameters. AUC(5-10 min) below percentile 10 of controls was associated with 50-70% progression to T1D regardless of age. Similar results were obtained for AUC(120-150 min). Clamp-derived first-phase C-peptide release can be used as an efficient and simple screening strategy in persistently autoAb(+) offspring and siblings of T1D patients to predict impending diabetes.

An evaluation of US patent 2015065565 (A1) for a new class of SGLT2 inhibitors for treatment 1 of type II diabetes mellitus.

PubMed

Jiang, Meiyan; Steyger, Peter S

2015-01-01

Type 2 diabetes mellitus (T2DM) is a growing and serious global health problem. Pharmacological inhibition of the sodium-glucose cotransporter-2 (SGLT2; SLC5A2) increases urinary glucose excretion, decreasing plasma glucose levels in an insulin-independent manner. Agents that inhibit SGLT2 have recently become available for clinical therapy of T2DM. The patent claims a new class of SGLT2 inhibitors: derivatives of dioxa-bicyclo[3.2.1]octane-2,3,4-triol (including ertugliflozin; PF-04971729). The invention describes the design, synthesis and pharmacological tests related to ertugliflozin, which could ultimately lead to efficacious therapy for T2DM alone or in combination with other anti-diabetic agents. Ertugliflozin is likely to be of great clinical significance in the near future. Continued analysis of ertugliflozin derivatives to now validate safe and efficacious treatment of T2DM in a larger number of clinical subjects over an extended period is needed to further support clinical utility. Identification, and discussion, of likely contra-indications is also needed.

Production of D-lactic acid from sugarcane bagasse using steam-explosion

NASA Astrophysics Data System (ADS)

Sasaki, Chizuru; Okumura, Ryosuke; Asakawa, Ai; Asada, Chikako; Nakamura, Yoshitoshi

2012-03-01

This study investigated the production of D-lactic acid from unutilized sugarcane bagasse using steam explosion pretreatment. The optimal steam pressure for a steaming time of 5 min was determined. By enzymatic saccharification using Meicellase, the highest recovery of glucose from raw bagasse, 73.7%, was obtained at a steam pressure of 20 atm. For residue washed with water after steam explosion, the glucose recovery increased up to 94.9% at a steam pressure of 20 atm. These results showed that washing with water is effective in removing enzymatic reaction inhibitors. After steam pretreatment (steam pressure of 20 atm), D-lactic acid was produced by Lactobacillus delbrueckii NBRC 3534 from the enzymatic hydrolyzate of steam-exploded bagasse and washed residue. The conversion rate of D-lactic acid obtained from the initial glucose concentration was 66.6% for the hydrolyzate derived from steam-exploded bagasse and 90.0% for that derived from the washed residue after steam explosion. These results also demonstrated that the hydrolyzate of steam-exploded bagasse (without washing with water) contains fermentation inhibitors and washing with water can remove them.

The effect of gestational diabetes on proliferation capacity and viability of human umbilical cord-derived stromal cells.

PubMed

Wajid, Nadia; Naseem, Rashida; Anwar, Sanam Saiqa; Awan, Sana Javaid; Ali, Muhammad; Javed, Sara; Ali, Fatima

2015-09-01

Stomal cells derived from Wharton's jelly of human umbilical cord (WJMSCs) are considered as the potential therapeutic agents for regeneration and are getting famous for stem cell banking. Our study aims to evaluate the effects of gestational diabetes on proliferation capacity and viability of WJMSCs. Mesenchymal stromal cells were isolated from Wharton's jelly of human umbilical cords from normal and gestational diabetic (DWJMSCs) mothers. Growth patterns of both types of cells were analyzed through MTT assay and population doubling time. Cell survival, cell death and glucose utilization were estimated through trypan blue exclusion assay, LDH assay and glucose detection assay respectively. Angiogenic ability was evaluated by immunocytochemistry and ELISA for VEGF A. Anti-cancerous potential was analyzed on HeLa cells. DWJMSCs exhibited low proliferative rate, increased population doubling time, reduced cell viability and increased cell death. Interestingly, DWJMSCs were found to have a reduced glucose utilization and anti-cancerous ability while enhanced angiogenic ability. Gestational diabetes induces adverse effects on growth, angiogenic and anti-cancerous potential of WJMSCs.

Integrated fiber optical and thermal sensor for noninvasive monitoring of blood and human tissue

NASA Astrophysics Data System (ADS)

Saetchnikov, Vladimir A.; Tcherniavskaia, Elina A.; Schiffner, Gerhard

2007-05-01

A novel concept of noninvasive monitoring of human tissue and blood based on optical diffuse reflective spectroscopy combined with metabolic heat measurements has been under development. A compact integrated fiber optical and thermal sensor has been developed. The idea of the method was to evaluate by optical spectroscopy haemoglobin and derivative concentrations and supplement with data associated with the oxidative metabolism of glucose. Body heat generated by glucose oxidation is based on the balance of capillary glucose and oxygen supply to the cells. The variation in glucose concentration is followed also by a difference from a distance (or depth) of scattered through the body radiation. So, blood glucose can be estimated by measuring the body heat and the oxygen supply. The sensor pickup contains of halogen lamp and LEDs combined with fiber optical bundle to deliver optical radiation inside and through the patient body, optical and thermal detectors. Fiber optical probe allows diffuse scattering measurement down to a depth of 2.5 mm in the skin including vascular system, which contributes to the control of the body temperature. The sensor pickup measures thermal generation, heat balance, blood flow rate, haemoglobin and derivative concentrations, environmental conditions. Multivariate statistical analysis was applied to convert various signals from the sensor pickup into physicochemical variables. By comparing the values from the noninvasive measurement with the venous plasma result, analytical functions for patient were obtained. Cluster analysis of patient groups was used to simplify a calibration procedure. Clinical testing of developed sensor is being performed.

Combined influence of basal media and fibroblast growth factor on the expansion and differentiation capabilities of adipose-derived stem cells.

PubMed

Ahearne, Mark; Lysaght, Joanne; Lynch, Amy P

2014-01-01

Interest in adipose-derived stem cells (ASCs) has increased in recent years due to their multi-linage differentiation capabilities. While much work has been done to optimize the differentiation media, few studies have focused on examining the influence of different expansion media on cell behavior. In this study, three basal media (low glucose Dulbecco's modified Eagle's medium (DMEM), high glucose DMEM and DMEM-F12) supplemented with or without fibroblast growth factor 2 (FGF) were examined to assess their suitability for expanding ASCs. Flow cytometry, colony-forming unit assays (CFU-Fs) and differentiation assays were utilized to study cell behavior. High glucose media CFU-Fs produced fewest colonies while the addition of FGF increased colony size. By passage 2, the majority of cells were positive for CD44, 45, 73, 90 and 105 and negative for CD14, 31 and 45, indicating a mesenchymal phenotype. A sub-population of CD34 positive cells was present among passage 2 cells; however, by passage 4 the cells were negative for CD34. FGF has a negative effective on passage 4 ASC adipogenesis and high glucose media plus FGF-enhanced osteogenic capacity of passage 4 ASCs. FGF supplemented basal media were most suitable for chondrogenesis. High glucose media plus FGF appeared to be the most beneficial for priming ASCs to induce a keratocyte phenotype. These findings demonstrate the reciprocal effect FGF and basal media have on ASCs. This research has implications for those interested regenerating bone, cartilage, cornea or adipose tissues.

Low glucose utilization and neurodegenerative changes caused by sodium fluoride exposure in rat's developmental brain.

PubMed

Jiang, Chunyang; Zhang, Shun; Liu, Hongliang; Guan, Zhizhong; Zeng, Qiang; Zhang, Cheng; Lei, Rongrong; Xia, Tao; Wang, Zhenglun; Yang, Lu; Chen, Yihu; Wu, Xue; Zhang, Xiaofei; Cui, Yushan; Yu, Linyu; Wang, Aiguo

2014-03-01

Fluorine, a toxic and reactive element, is widely prevalent throughout the environment and can induce toxicity when absorbed into the body. This study was to explore the possible mechanisms of developmental neurotoxicity in rats treated with different levels of sodium fluoride (NaF). The rats' intelligence, as well as changes in neuronal morphology, glucose absorption, and functional gene expression within the brain were determined using the Morris water maze test, transmission electron microscopy, small-animal magnetic resonance imaging and Positron emission tomography and computed tomography, and Western blotting techniques. We found that NaF treatment-impaired learning and memory in these rats. Furthermore, NaF caused neuronal degeneration, decreased brain glucose utilization, decreased the protein expression of glucose transporter 1 and glial fibrillary acidic protein, and increased levels of brain-derived neurotrophic factor in the rat brains. The developmental neurotoxicity of fluoride may be closely associated with low glucose utilization and neurodegenerative changes.

Astrocyte-derived adenosine is central to the hypnogenic effect of glucose

PubMed Central

Scharbarg, Emeric; Daenens, Marion; Lemaître, Frédéric; Geoffroy, Hélène; Guille-Collignon, Manon; Gallopin, Thierry; Rancillac, Armelle

2016-01-01

Sleep has been hypothesised to maintain a close relationship with metabolism. Here we focus on the brain structure that triggers slow-wave sleep, the ventrolateral preoptic nucleus (VLPO), to explore the cellular and molecular signalling pathways recruited by an increase in glucose concentration. We used infrared videomicroscopy on ex vivo brain slices to establish that glucose induces vasodilations specifically in the VLPO via the astrocytic release of adenosine. Real-time detection by in situ purine biosensors further revealed that the adenosine level doubles in response to glucose, and triples during the wakefulness period. Finally, patch-clamp recordings uncovered the depolarizing effect of adenosine and its A2A receptor agonist, CGS-21680, on sleep-promoting VLPO neurons. Altogether, our results provide new insights into the metabolically driven release of adenosine. We hypothesise that adenosine adjusts the local energy supply to local neuronal activity in response to glucose. This pathway could contribute to sleep-wake transition and sleep intensity. PMID:26755200

A Human Serum-Based Enzyme-Free Continuous Glucose Monitoring Technique Using a Needle-Type Bio-Layer Interference Sensor.

PubMed

Seo, Dongmin; Paek, Sung-Ho; Oh, Sangwoo; Seo, Sungkyu; Paek, Se-Hwan

2016-09-24

The incidence of diabetes is continually increasing, and by 2030, it is expected to have increased by 69% and 20% in underdeveloped and developed countries, respectively. Therefore, glucose sensors are likely to remain in high demand in medical device markets. For the current study, we developed a needle-type bio-layer interference (BLI) sensor that can continuously monitor glucose levels. Using dialysis procedures, we were able to obtain hypoglycemic samples from commercial human serum. These dialysis-derived samples, alongside samples of normal human serum were used to evaluate the utility of the sensor for the detection of the clinical interest range of glucose concentrations (70-200 mg/dL), revealing high system performance for a wide glycemic state range (45-500 mg/dL). Reversibility and reproducibility were also tested over a range of time spans. Combined with existing BLI system technology, this sensor holds great promise for use as a wearable online continuous glucose monitoring system for patients in a hospital setting.

Reforming and decomposition of glucose in an aqueous phase

NASA Technical Reports Server (NTRS)

Amin, S.; Reid, R. C.; Modell, M.

1975-01-01

Exploratory experiments have been carried out to study the decomposition of glucose, a typical carbohydrate, in a high temperature-high pressure water reactor. The objective of the study was to examine the feasibility of such a process to decompose cellulosic waste materials in long-term space missions. At temperatures below the critical point of water, glucose decomposed to form liquid products and char. Little gas was noted with or without reforming catalysts present. The rate of the primary glucose reaction increased significantly with temperature. Partial identification of the liquid phase was made and the C:H:O ratios determined for both the liquid and solid products. One of the more interesting results from this study was the finding that when glucose was injected into a reactor held at the critical temperature (and pressure) of water, no solid products formed. Gas production increased, but the majority of the carbon was found in soluble furans (and furan derivatives). This significant result is now being investigated further.

Sugaring-out extraction of acetoin from fermentation broth by coupling with fermentation.

PubMed

Dai, Jian-Ying; Ma, Lin-Hui; Wang, Zhuang-Fei; Guan, Wen-Tian; Xiu, Zhi-Long

2017-03-01

Acetoin is a natural flavor and an important bio-based chemical which could be separated from fermentation broth by solvent extraction, salting-out extraction or recovered in the form of derivatives. In this work, a novel method named as sugaring-out extraction coupled with fermentation was tried in the acetoin production by Bacillus subtilis DL01. The effects of six solvents on bacterial growth and the distribution of acetoin and glucose in different solvent-glucose systems were explored. The operation parameters such as standing time, glucose concentration, and volume ratio of ethyl acetate to fermentation broth were determined. In a system composed of fermentation broth, glucose (100%, m/v) and two-fold volume of ethyl acetate, nearly 100% glucose was distributed into bottom phase, and 61.2% acetoin into top phase without coloring matters and organic acids. The top phase was treated by vacuum distillation to remove solvent and purify acetoin, while the bottom phase was used as carbon source to produce acetoin in the next batch of fermentation.

Nucleocytoplasmic shuttling of hexokinase II in a cancer cell

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neary, Catherine L., E-mail: nearycl@umdnj.edu; Pastorino, John G.

2010-04-16

In yeast, the hexokinase type II enzyme (HXKII) translocates to the nucleus in the presence of excess glucose, and participates in glucose repression. However, no evidence has suggested a nuclear function for HXKII in mammalian cells. Herein, we present data showing nuclear localization of HXKII in HeLa cells, both by immunocytochemistry and subcellular fractionation. HXKII is extruded from the nucleus, at least in part, by the activity of the exportin 1/CrmA system, as demonstrated by increased nuclear expression and decreased cytoplasmic expression after incubation with leptomycin B, a bacterially-derived exportin inhibitor. Furthermore, cytoplasmic localization of HXKII is dependent on itsmore » enzymatic activity, as inhibiting HXKII activity using 2-deoxy-D-glucose (2DG) increased nuclear localization. This effect was more significant in cells incubated in the absence of glucose for 24 h prior to addition of 2DG. Regulated translocation of HXKII to the nucleus of mammalian cells could represent a previously unknown glucose-sensing mechanism.« less

Synthesis, optimization and structural characterization of a chitosan-glucose derivative obtained by the Maillard reaction.

PubMed

Gullón, Beatriz; Montenegro, María I; Ruiz-Matute, Ana I; Cardelle-Cobas, Alejandra; Corzo, Nieves; Pintado, Manuela E

2016-02-10

Chitosan (Chit) was submitted to the Maillard reaction (MR) by co-heating a solution with glucose (Glc). Different reaction conditions as temperature (40, 60 and 80 °C), Glc concentration (0.5%, 1%, and 2%, w/v), and reaction time (72, 52 and 24h) were evaluated. Assessment of the reaction extent was monitored by measuring changes in UV absorbance, browning and fluorescence. Under the best conditions, 2% (w/v) of Chit, 2% (w/v) of Glc at 60°C and 32 h of reaction time, a chitosan-glucose (Chit-Glc) derivative was purified and submitted to structural characterization to confirm its formation. Analysis of its molecular weight (MW) and the degree of substitution (DS) was carried out by HPLC-Size Exclusion Chromatography (SEC) and a colloid titration method, respectively. FT-IR and (1)H NMR were also used to analyze the functional groups and evaluate the introduction of Glc into the Chit molecule. According to our objectives, the results obtained in this work allowed to better understand the key parameters influencing the MR with Chit as well as to confirm the successful introduction of Glc into the Chit molecule obtaining a Chit-Glc derivative with a DS of 64.76 ± 4.40% and a MW of 210.37 kDa. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of GAPDH-derived antimicrobial peptides on sensitive yeasts cells: membrane permeability, intracellular pH and H+-influx/-efflux rates.

PubMed

Branco, Patrícia; Albergaria, Helena; Arneborg, Nils; Prista, Catarina

2018-05-01

Saccharomyces cerevisiae secretes antimicrobial peptides (AMPs) derived from glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which induce the death of several non-Saccharomyces yeasts. Previously, we demonstrated that the naturally secreted GAPDH-derived AMPs (i.e. saccharomycin) caused a loss of culturability and decreased the intracellular pH (pHi) of Hanseniaspora guilliermondii cells. In this study, we show that chemically synthesised analogues of saccharomycin also induce a pHi drop and loss of culturability in H. guilliermondii, although to a lesser extent than saccharomycin. To assess the underlying causes of the pHi drop, we evaluated the membrane permeability to H+ cations of H. guilliermondii cells, after being exposed to saccharomycin or its synthetic analogues. Results showed that the H+-efflux decreased by 75.6% and the H+-influx increased by 66.5% in cells exposed to saccharomycin at pH 3.5. Since H+-efflux via H+-ATPase is energy dependent, reduced glucose consumption would decrease ATP production and consequently H+-ATPase activity. However, glucose uptake rates were not affected, suggesting that the AMPs rather than affecting glucose transporters may affect directly the plasma membrane H+-ATPase or increase ATP leakage due to cell membrane disturbance. Thus, our study revealed that both saccharomycin and its synthetic analogues induced cell death of H. guilliermondii by increasing the proton influx and inhibiting the proton efflux.

Radioiodine remnant ablation in differentiated thyroid cancer after combined endogenous and exogenous TSH stimulation.

PubMed

Vrachimis, A; Schober, O; Riemann, B

2012-01-01

Radioiodine remnant ablation (RRA) after (near-)total thyroidectomy (TE) is a key element in patients with differentiated thyroid cancer (DTC). The use of exogenous TSH stimulation (rhTSH) prior to RRA has shown promising results as compared to conventional thyroid hormone withdrawal (THW). As yet, the efficacy of RRA after brief THW and single rhTSH administration has not been assessed. The study sample comprised 147 patients with DTC referred to our center between May 2008 and September 2010. All patients received TE with subsequent RRA. None of these 147 patients had evidence of distant metastasis. 93 patients had endogenous TSH stimulation 4-5 weeks after surgery (group I) and twenty-six received two rhTSH injections (group II). 28 patients were treated with a single rhTSH injection after a brief THW (group III). RRA-Efficacy was assessed three months after therapy by diagnostic whole-body scan and measurement of the tumour marker thyroglobulin (Tg) under TSH stimulation. Three categories of success were defined for remnant ablation. Based on the definition of successful remnant ablation no visible uptake and a Tg ≤ 2.0 ng/ml (category 1) was seen in 62/93 patients in group I, in 17/26 patients in group II (p = n.s.) and in 12/28 patients in group III (p < 0.05). Visible radioiodine uptake and a Tg ≤ 2.0 ng/ml (category 2) was seen in 16/28 patients of group III and thus significantly more frequent than in group I (28/93 patients) (p < 0.01). However, patients in group III (16/28 patients) and group II (8/26 patients) showed no significant difference in this category (p = n.s.). Visible radioiodine uptake and a Tg > 2.0 ng/ml (category 3) was found in 3/93 patients in group I and 1/26 patients in group II but in no patient in group III. The third strategy of remnant ablation using a single injection of rhTSH after a brief THW period resulted in a significant higher rate of patients with residual uptake in the thyroid bed and a Tg level below 2 ng/ml three months after remnant ablation in comparison to THW. However, the overall efficacy of the third protocol was not significantly different as compared to two rhTSH injections. Under the aspect of the supply shortage of rhTSH the combined endogenous and exogenous TSH stimulation may be an attractive alternative for remnant ablation in differentiated thyroid cancer.

Nutritional implications of olives and sugar: attenuation of post-prandial glucose spikes in healthy volunteers by inhibition of sucrose hydrolysis and glucose transport by oleuropein.

PubMed

Kerimi, Asimina; Nyambe-Silavwe, Hilda; Pyner, Alison; Oladele, Ebun; Gauer, Julia S; Stevens, Yala; Williamson, Gary

2018-03-09

The secoiridoid oleuropein, as found in olives and olive leaves, modulates some biomarkers of diabetes risk in vivo. A possible mechanism may be to attenuate sugar digestion and absorption. We explored the potential of oleuropein, prepared from olive leaves in a water soluble form (OLE), to inhibit digestive enzymes (α-amylase, maltase, sucrase), and lower [ 14 C(U)]-glucose uptake in Xenopus oocytes expressing human GLUT2 and [ 14 C(U)]-glucose transport across differentiated Caco-2 cell monolayers. We conducted 7 separate crossover, controlled, randomised intervention studies on healthy volunteers (double-blinded and placebo-controlled for the OLE supplement) to assess the effect of OLE on post-prandial blood glucose after consumption of bread, glucose or sucrose. OLE inhibited intestinal maltase, human sucrase, glucose transport across Caco-2 monolayers, and uptake of glucose by GLUT2 in Xenopus oocytes, but was a weak inhibitor of human α-amylase. OLE, in capsules, in solution or as naturally present in olives, did not affect post-prandial glucose derived from bread, while OLE in solution attenuated post-prandial blood glucose after consumption of 25 g sucrose, but had no effect when consumed with 50 g of sucrose or glucose. The combined inhibition of sucrase activity and of glucose transport observed in vitro was sufficient to modify digestion of low doses of sucrose in healthy volunteers. In comparison, the weak inhibition of α-amylase by OLE was not enough to modify blood sugar when consumed with a starch-rich food, suggesting that a threshold potency is required for inhibition of digestive enzymes in order to translate into in vivo effects.

Quantifying the contribution of grape hexoses to wine volatiles by high-precision [U¹³C]-glucose tracer studies.

PubMed

Nisbet, Mark A; Tobias, Herbert J; Brenna, J Thomas; Sacks, Gavin L; Mansfield, Anna Katharine

2014-07-16

Many fermentation volatiles important to wine aroma potentially arise from yeast metabolism of hexose sugars, but assessing the relative importance of these pathways is challenging due to high endogenous hexose substrate concentrations. To overcome this problem, gas chromatography combustion isotope ratio mass spectrometry (GC-C-IRMS) was used to measure high-precision (13)C/(12)C isotope ratios of volatiles in wines produced from juices spiked with tracer levels (0.01-1 APE) of uniformly labeled [U-(13)C]-glucose. The contribution of hexose to individual volatiles was determined from the degree of (13)C enrichment. As expected, straight-chain fatty acids and their corresponding ethyl esters were derived almost exclusively from hexoses. Most fusel alcohols and their acetate esters were also majority hexose-derived, indicating the importance of anabolic pathways for their formation. Only two compounds were not derived primarily from hexoses (hexanol and isobutyric acid). This approach can be extended to other food systems or substrates for studying precursor-product relationships.

Effect of N-benzoyl-D-phenylalanine, a new potential oral antidiabetic agent, in neonatal streptozotocin-induced diabetes in rats.

PubMed

Pari, Leelavinothan; Ashokkumar, Natarajan

2005-01-01

The present investigation was undertaken to study the effect of treatment with D-phenylalanine derivative and metformin in neonatal streptozotocin (nSTZ)-induced non-insulin-dependent diabetes mellitus (NIDDM) in rats. To induce NIDDM, a single dose injection of streptozotozin (STZ) (100 mg kg(-1); ip) was given to 2-day-old rats. After 10-12 weeks, rats weighing above 150 g were selected for screening in NIDDM model. They were checked for fasting blood glucose levels to conform the status of NIDDM. D-phenylalanine derivative (50, 100 and 200 mg kg(-1)) was administered per os (po) for 6 weeks to the rats with confirmed diabetes. A group of diabetic rats was also maintained and this group received metformin as comparative drug. Significant decrease in blood glucose with significant increase in plasma insulin was observed in group receiving 100 mg of D-phenylalanine derivative plus 500 mg of metformin.

Inhibitors of the alpha-ketoglutarate dehydrogenase complex alter [1-13C]glucose and [U-13C]glutamate metabolism in cerebellar granule neurons.

PubMed

Santos, Sónia Sá; Gibson, Gary E; Cooper, Arthur J L; Denton, Travis T; Thompson, Charles M; Bunik, Victoria I; Alves, Paula M; Sonnewald, Ursula

2006-02-15

Diminished activity of the alpha-ketoglutarate dehydrogenase complex (KGDHC), an important component of the tricarboxylic acid (TCA) cycle, occurs in several neurological diseases. The effect of specific KGDHC inhibitors [phosphonoethyl ester of succinyl phosphonate (PESP) and the carboxy ethyl ester of succinyl phosphonate (CESP)] on [1-13C]glucose and [U-13C]glutamate metabolism in intact cerebellar granule neurons was investigated. Both inhibitors decreased formation of [4-13C]glutamate from [1-13C]glucose, a reduction in label in glutamate derived from [1-13C]glucose/[U-13C]glutamate through a second turn of the TCA cycle and a decline in the amounts of gamma-aminobutyric acid (GABA), aspartate, and alanine. PESP decreased formation of [U-13C]aspartate and total glutathione, whereas CESP decreased concentrations of valine and leucine. The findings are consistent with decreased KGDHC activity; increased alpha-ketoglutarate formation; increased transamination of alpha-ketoglutarate with valine, leucine, and GABA; and new equilibrium position of the aspartate aminotransferase reaction. Overall, the findings also suggest that some carbon derived from alpha-ketoglutarate may bypass the block in the TCA cycle at KGDHC by means of the GABA shunt and/or conversion of valine to succinate. The results suggest the potential of succinyl phosphonate esters for modeling the biochemical and pathophysiological consequences of reduced KGDHC activity in brain diseases.

Glucose-Responsive Supramolecular Vesicles Based on Water-Soluble Pillar[5]arene and Pyridylboronic Acid Derivatives for Controlled Insulin Delivery.

PubMed

Gao, Lei; Wang, Tingting; Jia, Keke; Wu, Xuan; Yao, Chenhao; Shao, Wei; Zhang, Dongmei; Hu, Xiao-Yu; Wang, Leyong

2017-05-11

The stimuli-responsive behavior of supramolecular nanocarriers is crucial for their potential applications as smart drug delivery systems. We hereby constructed a glucose-responsive supramolecular drug delivery system based on the host-guest interaction between a water-soluble pillar[5]arene (WP5) and a pyridylboronic acid derivative (G) for insulin delivery and controlled release under physiological conditions. The approach represents the ideal treatment of diabetes mellitus. The drug loading and in vitro drug release experiments demonstrated that large molecular weight insulin could be encapsulated into the vesicles with high loading efficiency, which, to our knowledge, is the first example of small-size supramolecular vesicles with excellent encapsulation capacity of a large protein molecule. Moreover, FITC-labeled insulin was used to evaluate the release behavior of insulin, and it was demonstrated that high glucose concentration could facilitate the quick release of insulin, suggesting a smart drug delivery system for potential application in controlled insulin release only under hyperglycemic conditions. Finally, we demonstrated that these supramolecular nanocarriers have good cytocompatibility, which is essential for their further biomedical applications. The present study provides a novel strategy for the construction of glucose-responsive smart supramolecular drug delivery systems, which has potential applications for the treatment of diabetes mellitus. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of Human Myotubes-Derived Media on Glucose-Stimulated Insulin Secretion.

PubMed

Mizgier, Maria L; Cataldo, Luis R; Gutierrez, Juan; Santos, José L; Casas, Mariana; Llanos, Paola; Contreras-Ferrat, Ariel E; Moro, Cedric; Bouzakri, Karim; Galgani, Jose E

2017-01-01

Fasting to postprandial transition requires a tight adjustment of insulin secretion to its demand, so tissue (e.g., skeletal muscle) glucose supply is assured while hypo-/hyperglycemia are prevented. High muscle glucose disposal after meals is pivotal for adapting to increased glycemia and might drive insulin secretion through muscle-released factors (e.g., myokines). We hypothesized that insulin influences myokine secretion and then increases glucose-stimulated insulin secretion (GSIS). In conditioned media from human myotubes incubated with/without insulin (100 nmol/L) for 24 h, myokines were qualitatively and quantitatively characterized using an antibody-based array and ELISA-based technology, respectively. C57BL6/J mice islets and Wistar rat beta cells were incubated for 24 h with control and conditioned media from noninsulin- and insulin-treated myotubes prior to GSIS determination. Conditioned media from insulin-treated versus nontreated myotubes had higher RANTES but lower IL6, IL8, and MCP1 concentration. Qualitative analyses revealed that conditioned media from noninsulin- and insulin-treated myotubes expressed 32 and 23 out of 80 myokines, respectively. Islets incubated with conditioned media from noninsulin-treated myotubes had higher GSIS versus control islets ( p < 0.05). Meanwhile, conditioned media from insulin-treated myotubes did not influence GSIS. In beta cells, GSIS was similar across conditions. In conclusion, factors being present in noninsulin-stimulated muscle cell-derived media appear to influence GSIS in mice islets.

Xylitol prevents NEFA-induced insulin resistance in rats

PubMed Central

Kishore, P.; Kehlenbrink, S.; Hu, M.; Zhang, K.; Gutierrez-Juarez, R.; Koppaka, S.; El-Maghrabi, M. R.

2013-01-01

Aims/hypothesis Increased NEFA levels, characteristic of type 2 diabetes mellitus, contribute to skeletal muscle insulin resistance. While NEFA-induced insulin resistance was formerly attributed to decreased glycolysis, it is likely that glucose transport is the rate-limiting defect. Recently, the plant-derived sugar alcohol xylitol has been shown to have favourable metabolic effects in various animal models. Furthermore, its derivative xylulose 5-phosphate may prevent NEFA-induced suppression of glycolysis. We therefore examined whether and how xylitol might prevent NEFA-induced insulin resistance. Methods We examined the ability of xylitol to prevent NEFA-induced insulin resistance. Sustained ~1.5-fold elevations in NEFA levels were induced with Intralipid/heparin infusions during 5 h euglycaemic–hyperinsulinaemic clamp studies in 24 conscious non-diabetic Sprague-Dawley rats, with or without infusion of xylitol. Results Intralipid infusion reduced peripheral glucose uptake by ~25%, predominantly through suppression of glycogen synthesis. Co-infusion of xylitol prevented the NEFA-induced decreases in both glucose uptake and glycogen synthesis. Although glycolysis was increased by xylitol infusion alone, there was minimal NEFA-induced suppression of glycolysis, which was not affected by co-infusion of xylitol. Conclusions/interpretation We conclude that xylitol prevented NEFA-induced insulin resistance, with favourable effects on glycogen synthesis accompanying the improved insulin-mediated glucose uptake. This suggests that this pentose sweetener has beneficial insulin-sensitising effects. PMID:22460760

Human urine-derived stem cells play a novel role in the treatment of STZ-induced diabetic mice.

PubMed

Zhao, Tianxue; Luo, Deng; Sun, Yun; Niu, Xin; Wang, Yang; Wang, Chen; Jia, Weiping

2018-04-19

Human urine-derived stem cells (hUSCs) are a potential stem cell source for cell therapy. However, the effect of hUSCs on glucose metabolism regulation in type 1 diabetes was not clear. Therefore, the aim of the study was to evaluate whether hUSCs have protective effect on streptozotocin (STZ)-induced diabetes. hUSCs were extracted and cultivated with a special culture medium. Flow cytometry analysis was applied to detect cell surface markers. BALB/c male nude mice were either injected with high-dose STZ (HD-STZ) or multiple low-dose STZ (MLD-STZ). Serum and pancreatic insulin were measured, islet morphology and its vascularization were investigated. hUSCs highly expressed CD29, CD73, CD90 and CD146, and could differentiate into, at least, bone and fat in vitro. Transplantation of hUSCs into HD-STZ treated mice prolonged the median survival time and improved their blood glucose, and into those with MLD-STZ improved the glucose tolerance, islet morphology and increased the serum and pancreas insulin content. Furthermore, CD31 expression increased significantly in islets of BALB/c nude mice treated with hUSCs compared to those of un-transplanted MLD-STZ mice. hUSCs could improve the median survival time and glucose homeostasis in STZ-treated mice through promoting islet vascular regeneration and pancreatic beta-cell survival.

Hypolipidemic and hypoglycemic activities of a oleanolic acid derivative from Malva parviflora on streptozotocin-induced diabetic mice.

PubMed

Gutiérrez, Rosa Martha Pérez

2017-05-01

One new oleanolic acid derivative, 2α,3β,23α,29α tetrahydroxyolean-12(13)-en-28-oic acid (1) was isolated from the aerial parts of Malva parviflora. Their structure was characterized by spectroscopic methods. The hypolipidemic and hypoglycemic activities of 1 was analyzed in in streptozotocin (STZ)-nicotinamide-induced type 2 diabetes in mice (MD) and type 1 diabetes in streptozotocin-induced diabetic mice (SD). Triterpene was administered orally at doses of 20 mg/kg for 4 weeks. Organ weight, body weight, glucose, fasting insulin, cholesterol-related lipid profile parameters, glutamate oxaloacetate transaminase (SGOT), glutamate pyruvate transaminase (SGPT), serum alkaline phosphatase (SALP), glucokinase, hexokinase, glucose-6-phosphatase activities and glycogen in liver were measured after 4 weeks of treatment. The results indicated that 1 regulate glucose metabolism, lipid profile, lipid peroxidation, increased body weight, glucokinase and hexokinase activities inhibited triglycerides, total cholesterol, low density lipoproteins level, SGOT, SGPT, SALP, glycogen in liver and glucose-6-phosphatase. In addition, improvement of insulin resistance and protective effect for pancreatic β-cells, also 1 may changes the expression of pro-inflammatory cytokine (IL-6 and TNF-α levels) and enzymes (PAL2, COX-2, and LOX). The results suggest that 1 has hypolipidemic and hypoglycemic, anti-inflammatory, activities, improve insulin resistance and hepatic enzymes in streptozotocin-induced diabetic mice.

The Acute Effects of Simple Sugar Ingestion on Appetite, Gut-Derived Hormone Response, and Metabolic Markers in Men

PubMed Central

Yau, Adora M. W.; McLaughlin, John; Gilmore, William; Maughan, Ronald J.; Evans, Gethin H.

2017-01-01

This pilot study aimed to investigate the effect of simple sugar ingestion, in amounts typical of common ingestion, on appetite and the gut-derived hormone response. Seven healthy men ingested water (W) and equicaloric solutions containing 39.6 g glucose monohydrate (G), 36 g fructose (F), 36 g sucrose (S), and 19.8 g glucose monohydrate + 18 g fructose (C), in a randomised order. Serum concentrations of ghrelin, glucose dependent insulinotropic polypeptide (GIP), glucagon like peptide-1 (GLP-1), insulin, lactate, triglycerides, non-esterified fatty acids (NEFA), and d-3 hydroxybutyrate, were measured for 60 min. Appetite was measured using visual analogue scales (VAS). The ingestion of F and S resulted in a lower GIP incremental area under the curve (iAUC) compared to the ingestion of G (p < 0.05). No differences in the iAUC for GLP-1 or ghrelin were present between the trials, nor for insulin between the sugars. No differences in appetite ratings or hepatic metabolism measures were found, except for lactate, which was greater following the ingestion of F, S, and C, when compared to W and G (p < 0.05). The acute ingestion of typical amounts of fructose, in a variety of forms, results in marked differences in circulating GIP and lactate concentration, but no differences in appetite ratings, triglyceride concentration, indicative lipolysis, or NEFA metabolism, when compared to glucose. PMID:28216550

Effect of Human Myotubes-Derived Media on Glucose-Stimulated Insulin Secretion

PubMed Central

Cataldo, Luis R.; Gutierrez, Juan; Santos, José L.; Casas, Mariana; Contreras-Ferrat, Ariel E.; Moro, Cedric; Bouzakri, Karim

2017-01-01

Fasting to postprandial transition requires a tight adjustment of insulin secretion to its demand, so tissue (e.g., skeletal muscle) glucose supply is assured while hypo-/hyperglycemia are prevented. High muscle glucose disposal after meals is pivotal for adapting to increased glycemia and might drive insulin secretion through muscle-released factors (e.g., myokines). We hypothesized that insulin influences myokine secretion and then increases glucose-stimulated insulin secretion (GSIS). In conditioned media from human myotubes incubated with/without insulin (100 nmol/L) for 24 h, myokines were qualitatively and quantitatively characterized using an antibody-based array and ELISA-based technology, respectively. C57BL6/J mice islets and Wistar rat beta cells were incubated for 24 h with control and conditioned media from noninsulin- and insulin-treated myotubes prior to GSIS determination. Conditioned media from insulin-treated versus nontreated myotubes had higher RANTES but lower IL6, IL8, and MCP1 concentration. Qualitative analyses revealed that conditioned media from noninsulin- and insulin-treated myotubes expressed 32 and 23 out of 80 myokines, respectively. Islets incubated with conditioned media from noninsulin-treated myotubes had higher GSIS versus control islets (p < 0.05). Meanwhile, conditioned media from insulin-treated myotubes did not influence GSIS. In beta cells, GSIS was similar across conditions. In conclusion, factors being present in noninsulin-stimulated muscle cell-derived media appear to influence GSIS in mice islets. PMID:28286777

Glycogenolysis in astrocytes supports blood-borne glucose channeling not glycogen-derived lactate shuttling to neurons: evidence from mathematical modeling.

PubMed

DiNuzzo, Mauro; Mangia, Silvia; Maraviglia, Bruno; Giove, Federico

2010-12-01

In this article, we examined theoretically the role of human cerebral glycogen in buffering the metabolic requirement of a 360-second brain stimulation, expanding our previous modeling study of neurometabolic coupling. We found that glycogen synthesis and degradation affects the relative amount of glucose taken up by neurons versus astrocytes. Under conditions of 175:115 mmol/L (∼1.5:1) neuronal versus astrocytic activation-induced Na(+) influx ratio, ∼12% of astrocytic glycogen is mobilized. This results in the rapid increase of intracellular glucose-6-phosphate level on stimulation and nearly 40% mean decrease of glucose flow through hexokinase (HK) in astrocytes via product inhibition. The suppression of astrocytic glucose phosphorylation, in turn, favors the channeling of glucose from interstitium to nearby activated neurons, without a critical effect on the concurrent intercellular lactate trafficking. Under conditions of increased neuronal versus astrocytic activation-induced Na(+) influx ratio to 190:65 mmol/L (∼3:1), glycogen is not significantly degraded and blood glucose is primarily taken up by neurons. These results support a role for astrocytic glycogen in preserving extracellular glucose for neuronal utilization, rather than providing lactate to neurons as is commonly accepted by the current 'thinking paradigm'. This might be critical in subcellular domains during functional conditions associated with fast energetic demands.

Glycogenolysis in astrocytes supports blood-borne glucose channeling not glycogen-derived lactate shuttling to neurons: evidence from mathematical modeling

PubMed Central

DiNuzzo, Mauro; Mangia, Silvia; Maraviglia, Bruno; Giove, Federico

2010-01-01

In this article, we examined theoretically the role of human cerebral glycogen in buffering the metabolic requirement of a 360-second brain stimulation, expanding our previous modeling study of neurometabolic coupling. We found that glycogen synthesis and degradation affects the relative amount of glucose taken up by neurons versus astrocytes. Under conditions of 175:115 mmol/L (∼1.5:1) neuronal versus astrocytic activation-induced Na+ influx ratio, ∼12% of astrocytic glycogen is mobilized. This results in the rapid increase of intracellular glucose-6-phosphate level on stimulation and nearly 40% mean decrease of glucose flow through hexokinase (HK) in astrocytes via product inhibition. The suppression of astrocytic glucose phosphorylation, in turn, favors the channeling of glucose from interstitium to nearby activated neurons, without a critical effect on the concurrent intercellular lactate trafficking. Under conditions of increased neuronal versus astrocytic activation-induced Na+ influx ratio to 190:65 mmol/L (∼3:1), glycogen is not significantly degraded and blood glucose is primarily taken up by neurons. These results support a role for astrocytic glycogen in preserving extracellular glucose for neuronal utilization, rather than providing lactate to neurons as is commonly accepted by the current ‘thinking paradigm'. This might be critical in subcellular domains during functional conditions associated with fast energetic demands. PMID:20827264

Modulation of Mammary Stromal Cell Lactate Dynamics by Ambient Glucose and Epithelial Factors.

PubMed

Tobar, Nicolas; Porras, Omar; Smith, Patricio C; Barros, L Felipe; Martínez, Jorge

2017-01-01

Hyperglycemia is a risk factor for a variety of human cancers. Increased access to glucose and that tumor metabolize glucose by a glycolytic process even in the presence of oxygen (Warburg effect), provide a framework to analyze a particular set of metabolic adaptation mechanisms that may explain this phenomenon. In the present work, using a mammary stromal cell line derived from healthy tissue that was subjected to a long-term culture in low (5 mM) or high (25 mM) glucose, we analyzed kinetic parameters of lactate transport using a FRET biosensor. Our results indicate that the glucose pre-culture and soluble epithelial factors constitute a stimulus for lactate stromal production, factors that also modify the kinetic parameters and the monocarboxylate transporters expression in stromal cells. We also observed a vectorial flux of lactate from stroma to epithelial cells in a co-culture setting and found that the uptake of lactate by epithelial cells correlates with the degree of malignancy. Glucose preconditioning of the stromal cell stimulated epithelial motility. Our findings suggest that lactate generated by stromal cells in the high glucose condition stimulate epithelial migration. Overall, our results support the notion that glucose not only provides a substrate for tumor nutrition but also behaves as a signal promoting malignancy. J. Cell. Physiol. 232: 136-144, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Retinal lipid and glucose metabolism dictates angiogenesis through lipid sensor Ffar1

PubMed Central

Joyal, Jean-Sébastien; Sun, Ye; Gantner, Marin L.; Shao, Zhuo; Evans, Lucy P.; Saba, Nicholas; Fredrick, Thomas; Burnim, Samuel; Kim, Jin Sung; Patel, Gauri; Juan, Aimee M.; Hurst, Christian G.; Hatton, Colman J.; Cui, Zhenghao; Pierce, Kerry A.; Bherer, Patrick; Aguilar, Edith; Powner, Michael B.; Vevis, Kristis; Boisvert, Michel; Fu, Zhongjie; Levy, Emile; Fruttiger, Marcus; Packard, Alan; Rezende, Flavio A.; Maranda, Bruno; Sapieha, Przemyslaw; Chen, Jing; Friedlander, Martin; Clish, Clary B.; Smith, Lois E.H.

2016-01-01

Tissues with high metabolic rates often use lipid as well as glucose for energy, conferring a survival advantage during feast and famine.1 Current dogma suggests that high-energy consuming photoreceptors depend on glucose.2,3 Here we show that retina also uses fatty acids (FA) β-oxidation for energy. Moreover, we identify a lipid sensor Ffar1 that curbs glucose uptake when FA are available. Very low-density lipoprotein receptor (VLDLR), expressed in tissues with a high metabolic rate, facilitates the uptake of triglyceride-derived FA.4,5 Vldlr is present in photoreceptors.6 In Vldlr−/− retinas, Ffar1, sensing high circulating lipid levels despite decreased FA uptake5, suppresses glucose transporter Glut1. This impaired glucose entry into photoreceptors results in a dual lipid/glucose fuel shortage and reduction in the Krebs cycle intermediate α-ketoglutarate (KG). Low α-KG levels promote hypoxia-induced factor-1α (Hif1a) stabilization and vascular endothelial growth factor (Vegfa) secretion by starved Vldlr−/− photoreceptors, attracting neovessels to supply fuel. These aberrant vessels invading normally avascular photoreceptors in Vldlr−/− retinas are reminiscent of retinal angiomatous proliferation (RAP), a subset of neovascular age-related macular degeneration (AMD)7, associated with high vitreous VEGF levels in humans. Dysregulated lipid and glucose photoreceptor energy metabolism may therefore be a driving force in neovascular AMD and other retinal diseases. PMID:26974308

Fukushima-derived fission nuclides monitored around Taiwan: Free tropospheric versus boundary layer transport

NASA Astrophysics Data System (ADS)

Huh, Chih-An; Hsu, Shih-Chieh; Lin, Chuan-Yao

2012-02-01

The 2011 Fukushima nuclear accident in Japan was the worst nuclear disaster following the 1986 Chernobyl accident. Fission products (nuclides) released from the Fukushima plant site since March 12, 2011 had been detected around the northern hemisphere in about two weeks and also in the southern hemisphere about one month later. We report here detailed time series of radioiodine and radiocesium isotopes monitored in a regional network around Taiwan, including one high-mountain and three ground-level sites. Our results show several pulses of emission from a sequence of accidents in the Fukushima facility, with the more volatile 131I released preferentially over 134Cs and 137Cs at the beginning. In the middle of the time series, there was a pronounced peak of radiocesium observed in northern Taiwan, with activity concentrations of 134Cs and 137Cs far exceeding that of 131I during that episode. From the first arrival time of these fission nuclides and their spatial and temporal variations at our sampling sites and elsewhere, we suggest that Fukushima-derived radioactive nuclides were transported to Taiwan and its vicinity via two pathways at different altitudes. One was transported in the free troposphere by the prevailing westerly winds around the globe; the other was transported in the planetary boundary layer by the northeast monsoon wind directly toward Taiwan.

Discovery, SAR, and Radiolabeling of Halogenated Benzimidazole Carboxamide Antagonists as Useful Tools for (alpha)4(beta)1 Integrin Expressed on T- and B-cell Lymphomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carpenter, R D; Natarajan, A; Lau, E Y

2010-02-08

The cell surface receptor {alpha}{sub 4}{beta}{sub 1} integrin is an attractive yet poorly understood target for selective diagnosis and treatment of T- and B-cell lymphomas. This report focuses on the rapid microwave preparation of medicinally pertinent benzimidazole heterocycles, structure-activity relationships (SAR) of novel halobenzimidazole carboxamide antagonists 3-6, and preliminary biological evaluation of radioiodinated agents 7, 8, and 18. The I-125 derivative 18 had good tumor uptake (12 {+-} 1% ID/g at 24 h; 4.5 {+-} 1% ID/g at 48 h) and tumor:kidney ratio ({approx}4:1 at 24 h; 2.5:1 at 48 h) in xenograft murine models of B-cell lymphoma. Molecular homologymore » models of {alpha}{sub 4}{beta}{sub 1} integrin have predicted that docked halobenzimidazole carboxamides have the halogen atom in a suitable orientation for halogen-hydrogen bonding. These high affinity ({approx} pM binding) halogenated ligands are attractive tools for medicinal and biological use; the fluoro and iodo derivatives are potential radiodiagnostic ({sup 18}F) or radiotherapeutic ({sup 131}I) agents, whereas the chloro and bromo analogues could provide structural insight into integrin-ligand interactions through photoaffinity cross-linking/mass spectroscopy experiments, as well as co-crystallization X-ray studies.« less